EmeryStar Research Archive

Abstract

The observation of long-lived electronic coherence in a photosynthetic pigment–protein complex, the Fenna–Matthews–Olson (FMO) complex, is suggestive that quantum coherence might play a significant role in achieving the remarkable efficiency of photosynthetic electronic energy transfer (EET), although the data were acquired at cryogenic temperature [Engel GS, et al. (2007) Evidence for wavelike energy transfer through quantum coherence in photosynthetic systems. Nature 446:782–786]. In this paper, the spatial and temporal dynamics of EET through the FMO complex at physiological temperature are investigated theoretically. The numerical results reveal that quantum wave-like motion persists for several hundred femtoseconds even at physiological temperature, and suggest that the FMO complex may work as a rectifier for unidirectional energy flow from the peripheral light-harvesting antenna to the reaction center complex by taking advantage of quantum coherence and the energy landscape of pigments tuned by the protein scaffold. A potential role of quantum coherence is to overcome local energetic traps and aid efficient trapping of electronic energy by the pigments facing the reaction center complex.

Abstract

Photosynthesis makes use of sunlight to convert carbon dioxide into useful biomass and is vital for life on Earth. Crucial components for the photosynthetic process are antenna proteins, which absorb light and transmit the resultant excitation energy between molecules to a reaction centre. The efficiency of these electronic energy transfers has inspired much work on antenna proteins isolated from photosynthetic organisms to uncover the basic mechanisms at play. Intriguingly, recent work has documented that light-absorbing molecules in some photosynthetic proteins capture and transfer energy according to quantum-mechanical probability laws instead of classical laws at temperatures up to 180 K. This contrasts with the long-held view that long-range quantum coherence between molecules cannot be sustained in complex biological systems, even at low temperatures. Here we present two-dimensional photon echo spectroscopy measurements on two evolutionarily related light-harvesting proteins isolated from marine cryptophyte algae, which reveal exceptionally long-lasting excitation oscillations with distinct correlations and anti-correlations even at ambient temperature. These observations provide compelling evidence for quantum-coherent sharing of electronic excitation across the 5-nm-wide proteins under biologically relevant conditions, suggesting that distant molecules within the photosynthetic proteins are 'wired' together by quantum coherence for more efficient light-harvesting in cryptophyte marine algae.

Abstract

Hydrophilic materials such as Nafion can nucleate the buildup of interfacial water, which shows features different from bulk water. We investigated the effect of infrared (IR) light on a negatively charged, interfacial exclusion zone (EZ) and a positively charged proton zone (PZ) formed in the vicinity of Nafion. After irradiation for 5 min by mid-IR light, EZ size increased with an expansion ratio of 1.41. A significant expansion was also found in the size of PZ, equivalent to an increment of about 1.39 × 10¹⁶ molecules of hydronium ions. Thus, IR radiation not only builds EZ, but at the same time drives release of protons from the growing EZ to bulk water. Near-IR illumination also showed expansion of EZ and PZ water. These results imply that incident IR light not only promotes the build-up of interfacial water at the hydrophilic surface, but also provides a driving force for charge separation.

Abstract

Gold nanoparticles (AuNPs) have emerged as promising agents in the treatment of neurodegenerative diseases due to their unique physicochemical properties and ability to interact with biological systems at the nanoscale. This review summarizes recent advances in the application of AuNPs for neurodegenerative disorders, focusing on their roles in drug delivery, diagnostic imaging, and therapeutic interventions. The potential mechanisms by which AuNPs can cross the blood-brain barrier, reduce neurotoxicity, and modulate disease-related molecular pathways are discussed. Additionally, the review highlights current challenges, such as biocompatibility, toxicity, and targeted delivery, and outlines future perspectives for translating AuNP-based strategies into clinical practice. These developments suggest that gold nanoparticles hold significant promise for innovative approaches to the diagnosis and treatment of neurodegenerative diseases.

Abstract

Non-thermal atmospheric pressure plasma has been proposed as a new tool for various biological and medical applications. Plasma in close proximity to cell culture media or water creates reactive oxygen and nitrogen species containing solutions known as plasma-activated media (PAM) or plasma-activated water (PAW) - the latter even displays acidification. These plasma-treated solutions remain stable for several days with respect to the storage temperature. Recently, PAM and PAW have been widely studied for many biomedical applications. Here, we reviewed promising reports demonstrating plasma-liquid interaction chemistry and the application of PAM or PAW as an anti-cancer, anti-metastatic, antimicrobial, regenerative medicine for blood coagulation and even as a dental treatment agent. We also discuss the role of PAM on cancer initiation cells (spheroids or cancer stem cells), on the epithelial mesenchymal transition (EMT), and when used for metastasis inhibition considering its anticancer effects. The roles of PAW in controlling plant disease, seed decontamination, seed germination and plant growth are also considered in this review. Finally, we emphasize the future prospects of PAM, PAW or plasma-activated solutions in biomedical applications with a discussion of the mechanisms and the stability and safety issues in relation to humans.

Abstract

Plasma-activated water (PAW) is considered to be an effective anticancer agent due to the diverse aqueous reactive oxygen and nitrogen species (RONS: ROS and RNS), but the drawback of low dose and short duration of RONS in acidified PAW limits their clinical application. Herein, this Letter presents an innovative therapeutic avenue for cancer treatment with highly-effective alkaline PAW prepared by air surface plasma. This anticancer alkaline formulation is comprised of a rich mixture of highly chemical RONS and exhibited a prolonged half-life compared to acidified PAW. The H2O2, NO2−, and ONOO−/O2− concentrations in the alkaline PAW can reach up to 18-, 16-, and 14-fold higher than that in acidic PAW, and the half-life of these species was extended over 8-, 10-, and 26-fold, respectively. The synergistic potent redox action between these RONS with alkaline pH was shown to be more potent than acidic PAW for cancer cell inhibition in vitro. Furthermore, the alkaline PAW injection treatment also significantly inhibited tumor growth in tumor-bearing mice. The possible reasons are that the alkaline PAW would disturb the acid extracellular milieu leading to the inhibition of tumor growth and progression; moreover, the efficient and durable RONS with alkaline pH could induce significant cell apoptosis by altering cell biomolecules and participating apoptosis-related signaling pathways. These findings offer promising applications for developing a strategy with real potential for tumor treatment in clinical applications.

Abstract

Methylene blue (MB) is a well-established drug with a long history of use, owing to its diverse range of use and its minimal side effect profile. MB has been used classically for the treatment of malaria, methemoglobinemia, and carbon monoxide poisoning, as well as a histological dye. Its role in the mitochondria, however has elicited much of its renewed interest in recent years. MB can reroute electrons in the mitochondrial electron transfer chain directly from NADH to cytochrome c, increasing the activity of complex IV and effectively promoting mitochondrial activity while mitigating oxidative stress. In addition to its beneficial effect on mitochondrial protection, MB is also known to have robust effects in mitigating neuroinflammation. Mitochondrial dysfunction has been identified as a seemingly unifying pathological phenomenon across a wide range of neurodegenerative disorders, which thus positions methylene blue as a promising therapeutic. In both in vitro and in vivo studies, MB has shown impressive efficacy in mitigating neurodegeneration and the accompanying behavioral phenotypes in animal models for such conditions as stroke, global cerebral ischemia, Alzheimer’s disease, Parkinson’s disease, and traumatic brain injury. This review summarizes recent work establishing MB as a promising candidate for neuroprotection, with particular emphasis on the contribution of mitochondrial function to neural health. Furthermore, this review will briefly examine the link between MB, neurogenesis, and improved cognition in respect to age-related cognitive decline.

Abstract

studies evaluating effective drugs for health conditions are of crucial importance for public health. Methylene blue (MB) is an accessible synthetic drug that presents low toxicity and has been used in several health areas due to its effectiveness. Objective: this scoping review aims to provide a comprehensive overview of relevant research regarding the use of MB for the treatment of health conditions. Methods: a five-stage framework Arksey and O’maley scoping review was conducted. The literature was searched in Cochrane Library database using Mesh term “methylene blue”. Data were collected by two independent reviewers and submitted to descriptive synthesis. Results: The search resulted in 429 records, from which 16 were included after exclusion criteria were applied. The therapeutic use of MB was identified for acute conditions (malaria and septic shock), chronic conditions (discogenic back pain, bipolar disorder, refractory neuropathic pain, and post-traumatic stress disorder), and postoperative care (vasoplegic syndrome, and pain after haemorrhoidectomy, lumbar discectomy, and traumatic thoracolumbar fixation). Conclusion: there is much evidence emerging from clinical trials about the therapeutic use of MB for acute, chronic, and postoperative conditions; however, many gaps were identified, which open further avenues for future research.

Abstract

Methylene blue (MB), as the first fully man-made medicine, has a wide range of clinical applications. Apart from its well-known applications in surgical staining, malaria, and methemoglobinemia, the anti-oxidative properties of MB recently brought new attention to this century-old drug. Mitochondrial dysfunction has been observed in systematic aging that affects many different tissues, including the brain and skin. This leads to increaseding oxidative stress and results in downstream phenotypes under age-related conditions. MB can bypass Complex I/III activity in mitochondria and diminish oxidative stress to some degree. This review summarizes the recent studies on the applications of MB in treating age-related conditions, including neurodegeneration, memory loss, skin aging, and a premature aging disease, progeria.

Abstract

Our focus was to obtain an overall picture of the different beneficial properties of zeolite, based on its chemical and physical characteristics, which depend on zeolite absorption and exchange of ions. These characteristics make them very useful for various applications, including agriculture (as an animal feed additive and in food technology production), veterinary and human medicine, ecology, certain manufacturing, and cosmetics. Zeolite has pleiotropic effects, and the most important of them are detoxifying, antioxidant, and anti-inflammatory roles. We wanted to underline, with the review of the scientific literature, the positive medical beneficial effects of zeolite on the general health status.

Abstract

The natural clinoptilolite material is an inorganic crystal mineral called zeolite. It has been extensively studied and used in industrial applications and veterinary and human medicine due to positive effects on health. Limited data is available in the scientific literature about its effects on the levels of physiologically relevant minerals in the human organism. Accordingly, we performed a comprehensive and controlled monitoring of the relevant mineral and contaminants levels in human subjects supplemented with a certified clinoptilolite material within three clinical trials with different supplementation regimens. Effects of a registered and certified clinoptilolite material PMA-zeolite on selected mineral and metal levels were determined by standard biochemical methods and inductively coupled plasma mass spectrometry (ICP-MS) in the blood of subjects enrolled in three clinical trials: short-term (28 days, Mineral Metabolism and selected Blood Parameters study MMBP), medium-term (12 weeks, Morbus Crohn study), and long-term (4 years, Osteoporosis TOP study) supplementation. Lower concentrations were observed for copper (Cu) in patients with osteoporosis, which normalized again in the long-term supplementation trial, whereas sodium (Na) and calcium (Ca) levels diminished below the reference values in patients with osteoporosis. In the short- and long-term supplementation trials, increased levels of lead (Pb) were observed in PMA-zeolite-supplemented subjects, which decreased in the continued long-term supplementation trial. Increased levels of aluminum (Al) or Pb attributable to eventual leakage from the material into the bloodstream were not detected 1 h after intake in the short-term supplementation trial. Nickel (Ni) and Al were statistically significantly decreased upon long-term 4-year supplementation within the long-term supplementation trial, and arsenic (As) was statistically significantly decreased upon 12-weeks supplementation in the medium-term trial. Alterations in the measured levels for Na and Ca, as well as for Pb, in the long-term trial are probably attributable to the bone remodeling process. Checking the balance of the minerals Cu, Ca, and Na after 1 year of supplementation might be prescribed for PMA-supplemented patients with osteoporosis.

Abstract

Unique and outstanding physical and chemical properties of zeolite materials make them extremely useful in a variety of applications including agronomy, ecology, manufacturing, and industrial processes. Recently, a more specific application of one naturally occurring zeolite material, clinoptilolite, has been widely studied in veterinary and human medicine. Due to a number of positive effects on health, including detoxification properties, the usage of clinoptilolite-based products in vivo has increased enormously. However, concerns have been raised in the public about the safety of clinoptilolite materials for in vivo applications. Here, we review the scientific literature on the health effects and safety in medical applications of different clinoptilolite-based materials and propose some comprehensive, scientifically-based hypotheses on possible biological mechanisms underlying the observed effects on the health and body homeostasis. We focus on the safety of the clinoptilolite material and the positive medical effects related to detoxification, immune response, and the general health status.

Abstract

Zeolites are porous minerals with high absorbency and ion-exchange capacity. Their molecular structure is a dense network of AlO4 and SiO4 that generates cavities where water and other polar molecules or ions are inserted/exchanged. Even though there are several synthetic or natural occurring species of zeolites, the most widespread and studied is the naturally occurring zeolite clinoptilolite (ZC). ZC is an excellent detoxifying, antioxidant and anti-inflammatory agent. As a result, it is been used in many industrial applications ranging from environmental remediation to oral applications/supplementation in vivo in humans as food supplements or medical devices. Moreover, the modification as micronization of ZC (M-ZC) or tribomechanically activated zeolite clinoptilolite (TMAZ) or furthermore as double tribomechanically activated zeolite clinoptilolite (PMA-ZC) allows improving its benefits in preclinical and clinical models. Despite its extensive use, many underlying action mechanisms of ZC in its natural or modified forms are still unclear, especially in humans. The main aim of this review is to shed light on the geochemical aspects and therapeutic potentials of ZC with a vision of endorsing further preclinical and clinical research on zeolites, in specific on the ZC and its modified forms as a potential agent for promoting human brain health and overall well-being.

Summary

Gold compounds have been used for the treatment of rheumatoid arthritis and other autoimmune diseases for more than 75 years, but until now, how the metals work has been a mystery. Harvard Medical School researchers report in the Feb. 27 issue of Nature Chemical Biology that special forms of gold, platinum, and other classes of medicinal metals work by stripping bacteria and virus particles from the grasp of a key immune system protein.

Abstract

Ten milligram of pure gold foil was given by mouth for 16 days. Routine blood chemistry was done before and after gold therapy and repeated after 3 weeks of cessation of therapy. All the blood values were well within normal range and variations, except the enzymes—creatine phosphokinase and lactate dehydrogenase, which decreased substantially on gold foil ingestion indicating possible inhibition of these blood enzymatic activity by gold.

Abstract

Background

Impaired brain energy metabolism has been observed in many neurodegenerative diseases, including Parkinson’s disease (PD) and multiple sclerosis (MS). In both diseases, mitochondrial dysfunction and energetic impairment can lead to neuronal dysfunction and death. CNM-Au8® is a suspension of faceted, clean-surfaced gold nanocrystals that catalytically improves energetic metabolism in CNS cells, supporting neuroprotection and remyelination as demonstrated in multiple independent preclinical models. The objective of the Phase 2 REPAIR-MS and REPAIR-PD clinical trials was to investigate the effects of CNM-Au8, administered orally once daily for twelve or more weeks, on brain phosphorous-containing energy metabolite levels in participants with diagnoses of relapsing MS or idiopathic PD, respectively… Results… Conclusions…

Abstract

Inflammatory bowel diseases (IBD) and their main representatives, Crohn’s disease and ulcerative colitis, are worldwide health-care problems with constantly increasing frequency and still not fully understood pathogenesis. IBD treatment involves drugs such as corticosteroids, derivatives of 5-aminosalicylic acid, thiopurines, and others, with the goal to achieve and maintain remission of the disease. Nowadays, as our knowledge about IBD is continually growing, more specific and effective therapies at the molecular level are wanted. In our study, we tested novel gold complexes and their potential effect on inflammation and IBD in vitro, in silico, and in vivo. A series of new gold(III) complexes (TGS 404, 512, 701, 702, and 703) were designed and screened in the in vitro inflammation studies. In silico modeling was used to study the gold complexes’ structure vs. their activity and stability. Dextran sulphate sodium (DSS)-induced mouse model of colitis was employed to characterize the anti-inflammatory activity in vivo. Lipopolysaccharide (LPS)-stimulated RAW264.7 cell experiments proved the anti-inflammatory potential of all tested complexes. Selected on the bases of in vitro and in silico analyses, TGS 703 significantly alleviated inflammation in the DSS-induced mouse model of colitis, which was confirmed by a statistically significant decrease in the macro- and microscopic score of inflammation. The mechanism of action of TGS 703 was linked to the enzymatic and non-enzymatic antioxidant systems. TGS 703 and other gold(III) complexes present anti-inflammatory potential and may be applied therapeutically in the treatment of IBD.

Abstract

Masaru Emoto carried out very interesting experiments with water at critical point for freezing. He claimed that words expressing emotions have effect on the crystals formed in the process. Emoto reports that words with positive emotional contents produce beautiful crystals and those with negative emotional content generate ugly ones. Also music and even pictures are reported to have similar effect. Emoto had also experimented with rice in water and claims that the words with positive emotions content induce a metabolic process known as fermentation whereas those with negative emotional content tend to induce rottening. The experiments can be certainly criticized and people calling themselves skeptics have reacted violently to these claims. TGD inspired theory of consciousness and quantum biology suggests the presence of just this kind of effects and therefore one can make the working hypothesis that the effects are real, and see what the TGD based explanation for them could be. I will consider here the working hypothesis that the effects are real, and develop an explanation  based on TGD inspired quantum biology. The basic ingredients of the model are following: magnetic body (MB) carrying dark matter as heff/h=n phases of ordinary matter; communications between MB and biological body (BB) using dark photons able to transform to ordinary photons identifiable as bio-photons; the special properties of water explained in TGD framework by assuming dark component of water implying that criticality for freezing involves also quantum criticality, and the realization of genetic code and counterparts of the basic bio-molecules as dark proton sequences and as 3-chords consisting of light or sound providing a universal language allowing universal manner to express emotions in terms of bio-harmony realized as music of light or sound. The entanglement of water sample and the subject person (with MBs included) realized as flux tube connections would give rise to a larger conscious entity expressing emotions via language realized in terms of basic biomolecules in a universal manner by utilizing genetic code realized in terms of both dark proton sequences and music of light of light and sound.

Abstract

To create life, the first step should logically be the formation of the condensed system that defines a cell. If the original contents were dispersed widely, then those components would require condensation. Absent the needed condensation forces, those prime substances would have remained scattered, with no particular proclivity to form a cell. Energy is needed for the above-described process. Without energy for the splitting of water molecules, EZ cannot build. The required energy comes from light. Particularly effective, we found, is infrared light. The impacted water is presumably its EZ fraction, whose crystal-like structure allows for information-storage capability. Ordinary liquid water has no such capability: its randomly oriented, rapidly fluctuating molecules would be expected to show no capacity for retention of information. EZ water, on the other hand, seems practically “designed” to carry information.

Abstract

This global study analyzed data from the largest dataset ever studied in the Heart Rate Variability (HRV) biofeedback field, comprising 1.8 million user sessions collected from users of a mobile app during 2019 and 2020. We focused on HRV Coherence, which is linked to improved emotional stability and cognitive function. Positive emotions reported by users were associated with higher Coherence scores and more stable HRV frequencies. In contrast, negative emotions exhibited lower scores and more dispersed frequency distributions. The most common frequency associated with Coherence was identified at 0.10 Hz. However, many users with the highest levels of Coherence fell within a lower range from 0.04 to 0.10 Hz. Most users exhibited high stability (standard deviation < 0.012 Hz) in their coherence frequencies from session to session, and their stability within a given session increased with increasing Coherence. The insights gained from this extensive dataset suggest that by instructing users to breathe deeper and slower and find a rhythm that’s comfortable, they naturally find their unique resonant frequency. The findings provide a strong foundation for future research and the development of targeted interventions aimed at enhancing emotional and physiological well-being through HRV biofeedback and coherence practices.

Abstract

Brain waves have been detected and measured. These waves are electro-magnetic waves that flow through the membranes of cells and nerve fibers. Amplitude and frequency modulation (AM and FM) carries the information from cell to cell while the myelin coating prevents the information from being distorted. The Nodes of Ranvier are the regeneration stations so the information wave doesn’t die out. Interference of the waves creates holographic memories, coherent waves creating much stronger holograms than incoherent waves, which are far weaker than coherent waves. The autonomous nervous system carries health guided information (Placebo effect) the more coherent the signal, the stronger the health information is. Methods to create a positive, coherent mind and healthy body are given.

Abstract

(1) Background: The interaction between the human body and the Earth’s magnetic field at Schumann resonances (SRs) is one of the important fundamental questions of science that continues to be studied. The aim of this study was to create a working theoretical foundation for the interaction of the human body with SRs. (2) Methods: Extensive research was carried out in the literature with the aim of comprehensively presenting data on SRs and creating a working concept of their interaction with the human body. (3) Results: General data on SRs, a theoretical basis for justifying their interaction with the human body, possible mechanisms of influence and research results on the functioning of human internal organs were presented. (4) An interaction of the human body with SRs exists and has been scientifically proven. This interaction has been studied most significantly between SRs and the human nervous system. SRs affect functional indicators of the cardiovascular system: heart rate and blood pressure. Studying the influence of SRs on the course and pathogenesis of non-communicable diseases is a promising direction. Low-frequency SRs decrease the risk of developing acute myocardial infarction, and there is a tendency for them to promote cases of chronic kidney disease. SRs are an important external natural factor influencing the human body.

Results: The cold and hot extracts significantly reduced the angiotensin II, ACE, and aldosterone levels in the plasma. Furthermore, in the myocardium and aorta, decreased iNOS (inducible nitric oxide synthase) levels and elevated eNOS (endothelial nitric oxide synthase), as well as the rise in plasma NO levels, were reported with both extracts, but better results were displayed with the hot extract, leading to a potential antihypertensive effect. Additionally, the cold and hot Hibiscus extracts induced a cardioprotective effect through reducing necrosis, inflammation, and vacuolization that results from the induction of hypertension, an effect that was more prominent with the hot extract. Moreover, a comprehensive metabolomics approach using ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC–MS/MS) was able to trace the metabolites in each extraction.

Abstract

Hibiscus sabdariffa L. (Hs, roselle; Malvaceae) has been used traditionally as a food, in herbal drinks, in hot and cold beverages, as a flavouring agent in the food industry and as a herbal medicine. In vitro and in vivo studies as well as some clinical trials provide some evidence mostly for phytochemically poorly characterised Hs extracts. Extracts showed antibacterial, anti-oxidant, nephro- and hepato-protective, renal/diuretic effect, effects on lipid metabolism (anti-cholesterol), anti-diabetic and anti-hypertensive effects among others. This might be linked to strong antioxidant activities, inhibition of α-glucosidase and α-amylase, inhibition of angiotensin-converting enzymes (ACE), and direct vaso-relaxant effect or calcium channel modulation. Phenolic acids (esp. protocatechuic acid), organic acid (hydroxycitric acid and hibiscus acid) and anthocyanins (delphinidin-3-sambubioside and cyanidin-3-sambubioside) are likely to contribute to the reported effects.

More well designed controlled clinical trials are needed which use phytochemically characterised preparations. Hs has an excellent safety and tolerability record.

Abstract

The species Hibiscus sabdadariffa L. is originally from Africa. It has been distributed all over the world as an ornamental plant and it is consumed in several ways as infusion, salad dressings, marmalades, etc. However, its medical benefits are rarely studied. In this paper we present results from a clinical assay demonstrating the influence of hibiscus effects, presented as dry extracts in gel caps, on a general blood lipidic profile (LDL and HDL Cholesterol and triglycerides). We recruited 20 volunteers, 45 to 64 years old with the compromise of not changing food habits. They were divided into two groups; one of them received two 500 mg hibiscus dry gel caps treatment, three times a day for two months and the other group received same doses of placebo (Fructose) for the same period. Results showed a blood lipidic concentration reduction in those patients under hibiscus treatment statistically different (p < 0.05) as compared to control patients.

Abstract

Zobo leaves, also known as Roselle leaves are leaves of the Malvaceae plant Hibiscus sabdariffa, they are a common culinary ingredient as well as a traditional medicine in many countries including their role in treating various ailments and promoting overall health. The biological properties of the leaves of this plant have been studied and found to be of benefit to general improvement of health such biological properties as anti-inflammatory, anti-diabetic, anti-hypertensive, anti-cancer effects, potency against respiratory infections, skin diseases, and gastrointestinal disorders etcetera. These all stem from the bioactive components (anthocyanins, polyphenols, flavonoids, protocatechuic acid, malic acid, ascorbic acid, hibiscus acid contained in it. Our review focuses on these biological properties of Hibiscus sabdariffa and the bioactive compounds that are responsible for them. The nature, proximate composition including nutrient and mineral content, physicochemical properties and traditional uses of the plant according to different cultures are also included in our work. Finally, the importance of further research to fully understand the pharmacology and potential therapeutic applications of Roselle leaf and its bioactive compounds are highlighted.

Abstract

Context

Hibiscus sabdariffa (hibiscus) has been proposed to affect cardiovascular risk factors.

Objective

To review the evidence for the effectiveness of hibiscus in modulating cardiovascular disease risk markers, compared with pharmacologic, nutritional, or placebo treatments.

Data Sources

A systematic search of the Web of Science, Cochrane, Ovid (MEDLINE, Embase, AMED), and Scopus databases identified reports published up to June 2021 on randomized controlled trials using hibiscus as an intervention for lipid profiles, blood pressure (BP), and fasting plasma glucose levels in adult populations.

Data Extraction

Seventeen chronic trials were included. Quantitative data were examined using a random effects meta-analysis and meta-regression with trial sequential analysis to account for type I and type II errors.

Data Analysis

Hibiscus exerted stronger effects on systolic BP (−7.10 mmHg [95%CI, −13.00, −1.20]; I2 = 95%; P = 0.02) than placebo, with the magnitude of reduction greatest in those with elevated BP at baseline. Hibiscus induced reductions to BP similar to that resulting from medication (systolic BP reduction, 2.13 mmHg [95%CI, −2.81, 7.06], I2 = 91%, P = 0.40; diastolic BP reduction, 1.10 mmHg [95%CI, −1.55, 3.74], I2 = 91%, P = 0.42). Hibiscus also significantly lowered levels of low-density lipoprotein compared with other teas and placebo (−6.76 mg/dL [95%CI, −13.45, −0.07]; I2 = 64%; P = 0.05).

Conclusions

Regular consumption of hibiscus could confer reduced cardiovascular disease risk. More studies are warranted to establish an effective dose response and treatment duration.

Abstract

Zinc is an essential trace element and is required for many vital functions, including protein folding, as a co-factor for enzymes, in regulating gene expression, supporting cell membrane structure and cell signalling. It also has antioxidant and anti-inflammatory properties. As such, zinc plays an important role in growth and development, immune function, neurotransmission, vision and reproduction. Zinc deficiency is common, especially in developing countries, and can be due to dietary factors, malabsorption and alcoholic liver disease. Zinc supplementation at appropriate levels is considered safe, and has shown benefits in a wide range of medical conditions, including depression, diabetes, attention deficit hyperactivity disorder, male infertility, and the common cold in children.

Abstract

Zinc is a multipurpose trace element for the human body, as it plays a crucial part in various physiological processes, such as cell growth and development, metabolism, cognitive, reproductive, and immune system function. Its significance in human health is widely acknowledged, and this has led the scientific community towards more research that aims to uncover all of its beneficial properties, especially when compared to other essential metal ions. One notable area where zinc has shown beneficial effects is in the prevention and treatment of various diseases, including cancer. This review aims to explain the involvement of zinc in specific health conditions such as cancer, coronavirus disease 2019 (COVID-19) and neurological disorders like Alzheimer's disease, as well as its impact on the gut microbiome.

Abstract

Zinc is known to play a central role in the immune system, and zinc-deficient persons experience increased susceptibility to a variety of pathogens. The immunologic mechanisms whereby zinc modulates increased susceptibility to infection have been studied for several decades. It is clear that zinc affects multiple aspects of the immune system, from the barrier of the skin to gene regulation within lymphocytes. Zinc is crucial for normal development and function of cells mediating nonspecific immunity such as neutrophils and natural killer cells. Zinc deficiency also affects development of acquired immunity by preventing both the outgrowth and certain functions of T lymphocytes such as activation, Th1 cytokine production, and B lymphocyte help. Likewise, B lymphocyte development and antibody production, particularly immunoglobulin G, is compromised. The macrophage, a pivotal cell in many immunologic functions, is adversely affected by zinc deficiency, which can dysregulate intracellular killing, cytokine production, and phagocytosis. The effects of zinc on these key immunologic mediators is rooted in the myriad roles for zinc in basic cellular functions such as DNA replication, RNA transcription, cell division, and cell activation. Apoptosis is potentiated by zinc deficiency. Zinc also functions as an antioxidant and can stabilize membranes. This review explores these aspects of zinc biology of the immune system and attempts to provide a biological basis for the altered host resistance to infections observed during zinc deficiency and supplementation.

Abstract

The human body cannot store zinc reserves, so a deficiency can arise relatively quickly, e.g., through an improper diet. Severe zinc deficiency is rare, but mild deficiencies are common around the world. Many epidemiological studies have shown a relationship between the zinc content in the diet and the risk of cancer. The anti-cancer effect of zinc is most often associated with its antioxidant properties. However, this is just one of many possibilities, including the influence of zinc on the immune system, transcription factors, cell differentiation and proliferation, DNA and RNA synthesis and repair, enzyme activation or inhibition, the regulation of cellular signaling, and the stabilization of the cell structure and membranes. This study presents selected issues regarding the current knowledge of anti-cancer mechanisms involving this element.

Abstract

After the discovery of zinc deficiency in the 1960s, it soon became clear that zinc is essential for the function of the immune system. Zinc ions are involved in regulating intracellular signaling pathways in innate and adaptive immune cells. Zinc homeostasis is largely controlled via the expression and action of zinc "importers" (ZIP 1-14), zinc "exporters" (ZnT 1-10), and zinc-binding proteins. Anti-inflammatory and anti-oxidant properties of zinc have long been documented, however, underlying mechanisms are still not entirely clear. Here, we report molecular mechanisms underlying the development of a pro-inflammatory phenotype during zinc deficiency. Furthermore, we describe links between altered zinc homeostasis and disease development. Consequently, the benefits of zinc supplementation for a malfunctioning immune system become clear. This article will focus on underlying mechanisms responsible for the regulation of cellular signaling by alterations in zinc homeostasis. Effects of fast zinc flux, intermediate "zinc waves", and late homeostatic zinc signals will be discriminated. Description of zinc homeostasis-related effects on the activation of key signaling molecules, as well as on epigenetic modifications, are included to emphasize the role of zinc as a gatekeeper of immune function.

Abstract

This study reveals that fossil shungite samples exhibit antioxidant activity, can reduce oxidized components, and bind to free radicals. A sample of Sh20 (size fraction—20 μm) (1.30 mg equivalents of ascorbic acid/g of shungite; 3.46 mg equivalents of trolox/g of shungite; 0.99 mg equivalents of quercetin/g of shungite) had the maximal activity according to the amperometric method. The obtained data indicate that shungite has antioxidant properties, but these are approximately 1000 times less pronounced than those of quercetin. A ShT20 sample (size fraction—20 μm + heat treatment) was found to have the highest antioxidant activity against the 2,2-diphenyl-1-picrylhydrazyl radical and cytotoxicity. Further studies, including the optimization of the antioxidant extraction conditions of shungite, and the analysis of the qualitative and quantitative composition of the obtained extracts, are required for a more accurate interpretation of the results. Shungite can be applied as an alternative to activated carbon in water purification, due to its absorption, catalytic, antioxidant, regenerating, and antibacterial properties, as well as its high environmental safety and relatively low cost. It is possible to identify new structural forms of carbon within, and other valuable properties of, shungite substance, which will make it possible to create effective technologies for the practical use of shungite rocks, particularly in the production of fullerenes and other carbon nanoclusters.

Abstract

Dirt contains a powerful substance called humic acid. It is derived from organic matter in humus and peat within the soil. Chemically, humic acid is a mixture of acids that bind with charged ions making them good antioxidants and free radical scavengers. The charges on these molecules also allow the acid to move minerals and chemicals around the soil and the body. Because humic acid is too large to be absorbed into the blood stream, redistribution of toxins is not a concern making it ideal for detoxification. The compound binds substances in the digestive tract to be removed from the body. In addition, humic acid contains nutrients needed by the body and can strengthen our immune response.

Abstract

This 45-day clinical study examined the effects of oral humic acid supplementation (Activomin®) on gut microbiota in 14 healthy volunteers. Participants took 3 × 800 mg daily for 10 days, then 3 × 400 mg for 35 days. Using fluorescence in situ hybridization analysis of stool samples, researchers found that humic acids significantly increased total colonic microbiota concentrations by 20-30% without altering individual microbial diversity or profiles. The growth occurred in preexisting bacterial groups rather than introducing new species. Of 35 substantial bacterial groups, 24 showed increases ranging from 20-96%, while groups with initially low concentrations showed no response. The study concludes that humic acids profoundly affect healthy colonic microbiome and may be valuable for developing therapies to modulate gut bacteria.

Key Findings:

20-30% increase in total gut microbiota concentration. Individual microbial profiles remained unchanged - no new bacterial species introduced. 24 of 35 bacterial groups showed significant growth. No adverse effects on bacterial diversity or balance. Potential therapeutic applications for gut microbiome modulation.

Abstract

This clinical review presents what is known about the antiviral features of humic substances (HS) to the benefit of the clinical healthcare provider using available data in humeomics, the study of the soil humeome. It provides the reader with a working framework of historical studies and includes clinically relevant data with the goal of providing a broad appreciation of the antiviral potential of humic substances while also preparing for a translational leap into the clinical application of humic acid.

Abstract

Humic substances are organic ubiquitous components arising in the process of chemical and microbiological oxidation, generally called humification, the second largest process of the carbon cycle. The beneficial properties of these various substances can be observed in many fields of life and health, whether it is the impact on the human organism, as prophylactic as well as the therapeutic effects; animal physiology and welfare, which is widely used in livestock farming; or the impact of humic substances on the environment and ecosystem in the context of renewal, fertilization and detoxification. Since animal health, human health and environmental health are interconnected and mutually influencing, this work brings insight into the excellence of the use of humic substances as a versatile mediator contributing to the promotion of One Health.

Abstract

Chronic inflammatory diseases like diabetes are on a rise in the Western world. Based on the tsunami of new cases every year, new therapeutic measures must be considered. A promising avenue might involve the attenuation of underlying inflammation through natural health products (NHPs). This is because most NHPs have a rich history in traditional medicine and might be considered safer under appropriate doses and conditions. However, the biggest impediment in NHP research is that rarely do these products come with verified health benefits or dosing schedules established through modern scientific research. Fulvic acid (FvA), one such NHP, comes from humic substances produced by microorganisms in soil. Traditional medicine and modern research claim FvA can modulate the immune system, influence the oxidative state of cells, and improve gastrointestinal function; all of which are hallmarks of diabetes. This minireview outlines the available peer-reviewed research on FvA and examines its anecdotal health claims. We show that although available research has been minimal, there is substantial evidence to pursue FvA research in preventing chronic inflammatory diseases, including diabetes.

Abstract

This study investigated how fulvic acid (FA) affects inflammatory responses in human monocytes, specifically targeting homocysteine-induced inflammation linked to cardiovascular disease. Researchers used peripheral blood monocytes and U937 cells to examine fulvic acid's impact on cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) secretion. Multiple analytical techniques were employed including real-time PCR, ELISA, luciferase assays, and chromatin immunoprecipitation to determine the molecular mechanisms involved.

Key Findings:

Dose-dependent inhibition: Fulvic acid pretreatment blocked homocysteine-induced COX-2 expression in a concentration-dependent manner. Molecular mechanism identified: FA inhibited nuclear factor-κB (NF-κB) activation by blocking ERK and JNK phosphorylation pathways. Reduced inflammatory markers: FA decreased PGE2 secretion and COX-2 mRNA expression. Direct transcriptional effects: FA prevented NF-κB binding to COX-2 gene promoter regions

Clinical Significance:
This research provides molecular evidence for fulvic acid's anti-inflammatory properties, specifically its ability to interrupt homocysteine-mediated inflammatory pathways that contribute to cardiovascular disease. The findings support fulvic acid's potential as a pharmaceutical therapy for inflammation-related conditions.

Abstract

This Phase 1 double-blind clinical trial evaluated the safety and anti-inflammatory efficacy of carbohydrate-derived fulvic acid (CHD-FA) in 30 male volunteers with atopy. The study consisted of three parts: dose escalation (5-40 mL), short-term safety testing (3 days), and a crossover efficacy trial (1 week treatment + 1 week washout). Participants received up to 40 mL of 3.8% CHD-FA twice daily. Safety was monitored through ECG, physical exams, blood work, and health questionnaires. Allergic responses were measured using skin prick tests with participants' specific allergens.

Key Findings:

No severe adverse events occurred at any dosage level. Safety established up to 40 mL twice daily for one week. Significant decrease in skin prick test results indicating reduced allergic response. Anti-inflammatory effects confirmed at therapeutic doses. Results support earlier animal studies on CHD-FA safety and efficacy.

Clinical Significance:
CHD-FA demonstrates a favorable safety profile and shows promise as an anti-inflammatory agent for managing allergic conditions, warranting further clinical investigation.

Abstract

Carbohydrate derived fulvic acid (CHD-FA) is a heat stable low molecular weight, water soluble, cationic, colloidal material with proposed therapeutic properties. The aim of this study was to evaluate the antifungal activity of CHD-FA against Candida albicans, and to characterize its mode of action. A panel of C. albicans isolates (n = 50) derived from a range of clinical specimens were grown planktonically and as biofilms, and the minimum inhibitory concentrations determined. Scanning electron microscopy was performed to examine ultrastructural changes and different cell membrane assays were used to determine its mode of action. In addition, the role of C. albicans biofilm resistance mechanisms were investigated to determine their effects on CHD-FA activity. CHD-FA was active against planktonic and sessile C. albicans at concentrations 0.125 and 0.25% respectively, and was shown to be fungicidal, acting through disruption of the cell membrane activity. Resistance mechanisms, including matrix, efflux, and stress, had a limited role upon CHD-FA activity. Overall, based on the promising in vitro spectrum of activity and minimal biofilm resistance of the natural and cheap antiseptic CHD-FA, further studies are required to determine its applicability for clinical use.

Abstract

Transferrin has shown potential in the delivery of anticancer drugs into primarily proliferating cancer cells that over-express transferrin receptors. Fulvic acid has a wide range of biological and pharmacological activities which caused widespread concerns, the interaction of fulvic acid with human serum transferrin (Tf) has great significance for gaining a deeper insight about anticancer activities of fulvic acid. In this study, the mechanism of interaction between fulvic acid and Tf, has been investigated by using fluorescence quenching, thermodynamics, synchronous fluorescence and circular dichroism (CD) under physiological condition. Our results have shown that fulvic acid binds to Tf and form a new complex, and the calculated apparent association constants are 5.04 × 108 M−1, 5.48 × 107 M−1, 7.38 × 106 M−1 from the fluorescence quenching at 288 K, 298 K, and 310 K. The thermodynamic parameters indicate that hydrogen bonding and weak van der Waals are involved in the interaction between fulvic acid and Tf. The binding of fulvic acid to Tf causes the α-helix structure content of the protein to reduce, and resulting that peptide chains of Tf become more stretched. Our results have indicated a mechanism of the interaction between fulvic acid and Tf, which may provide information for possible design of methods to deliver drug molecules via transferrin to target tissues and cells effectively.

Abstract

Fulvic acid (FA) is known to promote electrochemical balance as a donor or a receptor possessing many biomedical functions. Nevertheless, the effect of FA on the anti-cancer activity has not been elucidated. In the current study, we first isolated FA from humus and investigated whether FA regulates immune-stimulating functions, such as production of nitric oxide (NO), in RAW 264.7 cells. Our data showed that FA slightly enhances cell viability in a dose-dependent manner and secretion of NO from RAW 264.7 cells. It upregulated the protein and mRNA expression of inducible NO synthesis (iNOS). In addition, FA enhanced the DNA-binding activity of nuclear factor-κB (NF-κB) in RAW 264.7 cells; the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC) effectively attenuated the expression of FA-stimulated iNOS, suggesting that FA stimulates NF-κB to promote iNOS and NO production. Finally, FA-stimulated culture media (FA-CM) from RAW 264.7 cells were collected and MCA-102 fibrosarcoma cells were cultured in this media. The FA-CM augmented MCA-102 fibrosarcoma cell apoptosis; however, an NO inhibitor NG-monomethyl-l-arginine (NMMA) slightly inhibited the FA-CM-mediated MCA-102 fibrosarcoma cell apoptosis, which was accompanied by low levels of NO. In the present study, we found that FA induces the generation of NO and iNOS in RAW 264.7 cells by inducing NF-κB activation; however, NO did not significantly stimulate MCA-102 fibrosarcoma cell apoptosis in the current study. In addition, FA-CM enhanced cell death in various human cancer cells such as Hep3B, LNCaP, and HL60. Taken together, FA most likely stimulates immune-modulating molecules such as NO and induces cancer cell apoptosis.

Abstract

The aim of this study was to determine whether serum lipid composition and lipolytic activities in alcoholinduced liver dystrophy were modified by the co-administration of polyunsaturated phosphatidylcholine (PPC). Chronic alcohol intoxication was induced in rats by intragastric ethanol administration of 3.5 g/kg body weight per day over 56 days. Aqueous PPC suspension was given intragastrally in doses of 100 and 300 mg/kg body weight. Chronic alcohol intoxication led to the development of protein and lipid dystrophy of hepatocytes. PPC partially prevented alcoholic injury of the liver cells and had a normalizing effect on cholesterol esterification, lipolysis of lipoproteins and on the fatty acid composition of the main lipoprotein classes.

Abstract

Six normal men were fed formula diets containing either highly saturated fat (cocoa butter, iodine value 32) or polyunsaturated fat (corn oil, iodine value 125). The sterol balance technique was used to compare the changes in serum cholesterol concentration with the excretion of fecal steroids. The method used for the analysis of fecal steroids was chemical, with a final identification and quantification by gas-liquid chromatography. It was confirmed that the chemical method for fecal steroid analysis was accurate and reproducible. The three dietary periods were each 3 wk in length. In sequence, cocoa butter (period I), corn oil, and cocoa butter (period III) were fed at 40% of the total calories. All diets were cholesterol free, contained similar amounts of plant sterols, and were identical in other nutrients. Corn oil had a hypocholesterolemic effect. Mean serum cholesterol concentrations were 222 mg/100 ml (cocoa butter, period I), 177 during corn oil, and 225 after the return to cocoa butter. Individual fecal steroids were determined from stools pooled for 7 days. Both neutral steroids and bile acids were altered significantly by dietary polyunsaturated fat. The change in bile acid excretion was considerably greater than the change in neutral steroids. Corn oil caused a greater fecal excretion of both deoxycholic and lithocholic acids. The total mean excretion (milligrams per day) of fecal steroids was 709 for cocoa butter (period I), 915 for corn oil, and 629 for the second cocoa butter period. The enhanced total fecal steroid excretion by the polyunsaturated fat of corn oil created a negative cholesterol balance vis-à-vis the saturated fat of cocoa butter. The hypocholesterolemic effect of polyunsaturated fat was associated with total fecal sterol excretion twice greater than the amount of cholesterol calculated to leave the plasma. This finding suggested possible loss of cholesterol from the tissues as well.

Abstract

Phosphatidylcholine (PC) is the major phospholipid component of all plasma lipoprotein classes. PC is the only phospholipid which is currently known to be required for lipoprotein assembly and secretion. Impaired hepatic PC biosynthesis significantly reduces the levels of circulating very low density lipoproteins (VLDLs) and high density lipoproteins (HDLs). The reduction in plasma VLDLs is due in part to impaired hepatic secretion of VLDLs. Less PC within the hepatic secretory pathway results in nascent VLDL particles with reduced levels of PC. These particles are recognized as being defective and are degraded within the secretory system by an incompletely defined process that occurs in a post-endoplasmic reticulum compartment, consistent with degradation directed by the low-density lipoprotein receptor and/or autophagy. Moreover, VLDL particles are taken up more readily from the circulation when the PC content of the VLDLs is reduced, likely due to a preference of cell surface receptors and/or enzymes for lipoproteins that contain less PC. Impaired PC biosynthesis also reduces plasma HDLs by inhibiting hepatic HDL formation and by increasing HDL uptake from the circulation. These effects are mediated by elevated expression of ATP-binding cassette transporter A1 and hepatic scavenger receptor class B type 1, respectively. Hepatic PC availability has recently been linked to the progression of liver and heart disease. These findings demonstrate that hepatic PC biosynthesis can regulate the amount of circulating lipoproteins and suggest that hepatic PC biosynthesis may represent an important pharmaceutical target. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease.

Abstract

The liver plays a central role in regulating cholesterol and low-density lipoprotein (LDL) homeostasis across various animal species, including humans. This review examines the mechanisms by which the liver maintains cholesterol balance, focusing on cholesterol biosynthesis, uptake, and excretion, as well as the metabolism and clearance of LDL particles. The influence of dietary fats, genetic variation, and species-specific differences on hepatic cholesterol and LDL regulation are discussed. Evidence is presented on how alterations in liver function impact plasma LDL levels and overall cholesterol homeostasis, highlighting the importance of hepatic pathways in the development of hypercholesterolemia and related cardiovascular risk. Understanding these processes provides insight into potential therapeutic targets for managing dyslipidemia and preventing atherosclerotic disease

Abstract

Beneficial effects of dietary phospholipids (PLs) have been mentioned since the early 1900's in relation to different illnesses and symptoms, e.g. coronary heart disease, inflammation or cancer. This article gives a summary of the most common therapeutic uses of dietary PLs to provide an overview of their approved and proposed benefits; and to identify further investigational needs.

From the majority of the studies it became evident that dietary PLs have a positive impact in several diseases, apparently without severe side effects. Furthermore, they were shown to reduce side effects of some drugs. Both effects can partially be explained by the fact that PL are highly effective in delivering their fatty acid (FA) residues for incorporation into the membranes of cells involved in different diseases, e.g. immune or cancer cells. The altered membrane composition is assumed to have effects on the activity of membrane proteins (e.g. receptors) by affecting the microstructure of membranes and, therefore, the characteristics of the cellular membrane, e.g. of lipid rafts, or by influencing the biosynthesis of FA derived lipid second messengers. However, since the FAs originally bound to the applied PLs are increased in the cellular membrane after their consumption or supplementation, the FA composition of the PL and thus the type of PL is crucial for its effect. Here, we have reviewed the effects of PL from soy, egg yolk, milk and marine sources. Most studies have been performed in vitro or in animals and only limited evidence is available for the benefit of PL supplementation in humans. More research is needed to understand the impact of PL supplementation and confirm its health benefits.

Abstract

Aim: Although essential phospholipids (EPL) from soybean are often used in membrane-associated disorders and diseases, their high quality of purification and effects on prevalent liver diseases, especially on fatty liver diseases (FLDs) of different origin, are still widely unknown and a matter of continuous active research. The aim of this article is to review, discuss, and summarize the available results of EPL in the treatment of FLD.

Methods: Database research was carried out on Medline, Embase, Cochrane Library, country-specific journals, and follow-up literature citations for relevant hepatogastroenterological articles published between 1988 and 2014. We searched for and reviewed only those papers that indicated minimum extraction amount of 72% (3-sn-phosphatidyl)choline from soybean as being necessary to treat patients with a considerable amount of 1,2-dilinoleoylphosphatidylcholine as a key component in EPL.

Results: EPL has a well-established mode of action, therapeutic effectiveness, and lack of toxicity, which ensures clinically relevant efficacy-to-safety ratio. It influences membrane- dependent cellular functions and shows anti-inflammatory, antioxidant, antifibrogenic, anti apoptotic, membrane-protective, and lipid-regulating effects. Due to its positive effects on membrane composition and functions, it accelerates the improvement or normalization of subjective symptoms; pathological, clinical, and biochemical findings; hepatic imaging; and liver histology. It is justified to administer EPL together with other therapeutic measurements in the liver.

Conclusion: Pharmacological and clinical results confirm the efficacy of EPL in the treatment of FLD.

Abstract

Background: Phosphatidylcholine (PC) is the predominant phospholipid associated with high density lipoproteins (HDL). Although the hepatic uptake of cholesteryl esters from HDL is well characterized, much less is known about the fate of PC associated with HDL. Thus, we investigated the uptake and subsequent metabolism of HDL-PC in primary mouse hepatocytes.

Methods and results: The absence of scavenger receptor-BI resulted in a 30% decrease in cellular incorporation of [(3)H]PC whereas [(3)H]cholesteryl ether uptake was almost completely abolished. Although endocytosis is not involved in the uptake of cholesteryl esters from HDL, we demonstrate that HDL internalization accounts for 40% of HDL-PC uptake. Extracellular remodeling of HDL by secretory phospholipase A(2) significantly enhances HDL lipid uptake. HDL-PC taken up by hepatocytes is partially converted to triacylglycerols via PC-phospholipase C-mediated hydrolysis of PC and incorporation of diacylglycerol into triacylglycerol. The formation of triacylglycerol is independent of scavenger receptor-BI and occurs in extralysosomal compartments.

Conclusions and general significance: These findings indicate that HDL-associated PC is incorporated into primary hepatocytes via a pathway that differs significantly from that of HDL-cholesteryl ester, and shows that HDL-PC is more than a framework molecule, as evidenced by its partial conversion to hepatic triacylglycerol.

Abstract

Previous studies have shown that polyunsaturated ruminant fats in the diets of human subjects cause an increase in cholesterol and bile acid excretion during the first 3 weeks of such diets. The present studies were designed to compare the effects of polyunsaturated (P) and conventional (S) ruminant fats at two levels of dietary cholesterol intake: a higher (HC) and lower (LC). Four study periods, each of about 3 weeks' duration, were conducted in 5 healthy subjects providing these dietary combinations: HCS, HCP, LCS, LCP. Neutral sterols and bile acids were measured in the feces, and sterol balances were calculated. Plasma cholesterol levels were significantly lower with P than with S diets at both HC and LC intakes. Changes attributable to differences in fatty acids and to differences in cholesterol intake appeared to exert independent effects. The major changes occurred in lipoproteins with density 1.019-1.045. Cholesterol absorption expressed as a percentage of the dietary intake was not significantly different with the four diets. Neutral sterol excretion of probable endogenous origin and bile acid excretion were significantly higher during the HCP than during the HCS periods, but the difference between LCP and LCS periods was less marked. Net sterol excretion was therefore significantly greater with HCP and LCP than with HCS and LCS diets, the differences being greater at HC than at LC intakes. Comparisons of diets with similar fatty acid but differing cholesterol intakes showed lower net sterol excretion with HCS than with LCS diets (presumably due to suppression by HC by cholesterol synthesis), but this difference was not seen between HCP and LCP diets. This finding, together with greater sterol excretion with HCP than with HCS diets, showed that enhanced sterol excretion with polyunsaturated fat was potentiated with higher cholesterol intake. This enhanced excretion was generally greater during the first than during the second 3-week period of polyunsaturated fat.

Abstract

Unesterified cholesterol (UC) that is taken up by the liver from lipoproteins is rapidly mixed by exchange with liver UC. Thus, it is not possible to quantitate the transport of UC from different lipoproteins into bile using radiolabeled UC. However, plant sterols do not exchange with UC and are secreted in bile with the same kinetics as UC. To compare the contribution to bile of sterols from different lipoproteins, we perfused isolated rat livers with VLDL, LDL, and HDL that were obtained from patients with hereditary phytosterolemia and were rich in plant sterols. After 30-min recirculating perfusions, hepatic concentrations of plant sterols were not different after different lipoproteins were perfused. However, biliary plant sterol secretion was markedly different: with the perfusion of either VLDL or LDL there was no increase in plant sterols in bile, but with perfusion of HDL, the secretion of plant sterols was increased two- to threefold (P = 0.0005). The increase in biliary plant sterols was detected 5-10 min after HDL was added to perfusates and was similarly large for each of three individual plant sterols that was tracked. Results show that when sterol transport from lipoproteins into bile can be determined, only HDL provides a vehicle for UC elimination in bile that is consistent with its putative function in reverse cholesterol transport.

Abstract

The absorption of cholesterol has been studied in man by perfusing the upper jejunum with a micellar solution of bile salt, 1-monoglyceride, and cholesterol-(14)C, with a triple lumen tube with collection sites 50 cm apart. The absorption of micellar components between the collection sites was calculated from their concentration changes relative to those of the watersoluble marker, polyethylene glycol. Control experiments were performed with cholesterol-free perfusions of saline or bile salt-monoglyceride solutions. Steady state conditions were obtained.Each of the components of the micelle was absorbed to a different extent during passage through the test segment of jejunum. Bile salt was not absorbed (mean, -3%), but micellar monoglyceride was rapidly hydrolyzed and absorbed almost completely (mean, 98%). Cholesterol radioactivity was absorbed to an intermediate extent (mean, 73%), and the absorption of chemically determined cholesterol (mean, 46%) indicated that much of the disappearance of radioactivity represented true absorption and not simple exchange. The specific activity of the perfused cholesterol fell during passage through the loop. This fall was interpreted as signifying the continuous addition of nonradioactive endogenous cholesterol by the test segment. However, the decrease in specific activity may also be considered to signify exchange, in that nonradioactive molecules entered the lumen as radioactive molecules were absorbed. Plant sterols appeared in the intestinal contents during the perfusion and must have been contributed by the perfused segment. The perfusate and samples taken from the upper and lower collection sites were examined by ultracentrifugation to define the physical state of cholesterol. It was found that cholesterol in the perfusate or upper collection site samples did not sediment, but that 23% of the cholesterol in the lower collection site samples was sedimentable (mean of three experiments); bile salt, as control, was not sedimentable. Solubility experiments in model systems showed that cholesterol possessed low solubility in bile salt solution; its solubility increased markedly and in linear proportion to the amount of fatty acid or monoglyceride or both that was added to the bile salt solution. These findings suggest that polar lipid such as fatty acid or monoglyceride as well as bile salt is essential for normal micellar solubilization of cholesterol in intestinal content. They suggest the necessity of considering an insoluble sedimentable phase of particulate sterol in intestinal content as well as an oil and micellar phase for a complete description of sterol absorption. The marked difference in the rates of absorption of individual micellar components suggests that micellar lipid is not absorbed as an intact aggregate and is consistent with the view that polar lipid such as fatty acid is absorbed in molecular form by diffusion from a micellar solution. The experiments confirm previous findings demonstrating that fat absorption without bile salt absorption occurs in the upper small intestine in man.

Abstract

The reverse cholesterol transport pathway (RCT) is the focus of many cholesterol-lowering therapies. By way of this pathway, excess cholesterol is collected from peripheral tissues and delivered back to the liver and gastrointestinal tract for excretion from the body. For a long time this removal via the hepatobiliary secretion was considered to be the sole route involved in the RCT. However, observations from early studies in animals and humans already pointed towards the possibility of another route. In the last few years it has become evident that a non-biliary cholesterol secretion pathway exists in which the intestine plays a central role. This transintestinal cholesterol efflux (TICE) pathway contributes significantly to the total fecal neutral sterol excretion. Moreover, recent studies have shown that TICE is also sensitive to stimulation. As a consequence, the direct role of cholesterol secretion from blood via TICE makes the intestine a suitable and approachable target for cholesterol removal from the body and possibly reduction of atherosclerosis. In this review, the discovery and recent findings contributing to understanding the mechanism of TICE will be discussed.

Abstract

Apart from alcohol, there are other factors that may induce complications, which resemble alcohol-related liver disorders. In particular, obesity has been brought into focus as a risk factor for fatty liver disease. The term “non-alcoholic” fatty liver disease is commonly used to distinguish between obesity-related and alcohol-related hepatic steatosis. This review uses the epidemiological perspective to critically assess whether it is necessary and useful to differentiate between alcoholic and “non-alcoholic” fatty liver disease. The MEDLINE database was searched using the PubMed search engine, and a review of reference lists from original research and review articles was conducted. The concept to distinguish between alcoholic and “non-alcoholic” fatty liver disease is mainly based on specific pathomechanisms. This concept has, however, several limitations including the common overlap between alcohol misuse and obesity-related metabolic disorders and the non-consideration of additional causal factors. Both entities share similar histopathological patterns. Studies demonstrating differences in clinical presentation and outcome are often biased by selection. Risk factor reduction is the main principle of prevention and treatment of both disease forms. In conclusion, alcoholic and “non-alcoholic” fatty liver diseases are one and the same disease caused by different risk factors. A shift from artificial categories to a more general approach to fatty liver disease as a multicausal disorder may optimize preventive strategies and help clinicians more effectively treat patients at the individual level.

Abstract

In 1850, Theodore Gobley, working in Paris, described a substance, 'lecithine', which he named after the Greek 'lekithos' for egg yolk. Adolph Strecker noted in 1862 that when lecithin from bile was heated, it generated a new nitrogenous chemical that he named 'choline'. Three years later, Oscar Liebreich identified a new substance, 'neurine', in the brain. After a period of confusion, neurine and choline were found to be the same molecule, and the name choline was adapted. Lecithin was eventually characterized chemically as being phosphatidylcholine. In 1954, Eugene Kennedy described the cytidine 5-dihphosphocholine pathway by which choline is incorporated into phosphatidylcholine. A second route, the phosphatidylethanolamine-N-methyltransferase pathway, was identified by Jon Bremer and David Greenberg in 1960. The role of choline as part of the neurotransmitter acetylcholine was established by Otto Loewi and Henry Dale. Working in the 1930s at the University of Toronto, Charles Best showed that choline prevented fatty liver in dogs and rats. The importance of choline as an essential nutrient for human health was determined in the 1990s through controlled feeding studies in humans. Recently, an understanding of the role of genetic variation in setting the dietary requirement for choline in people is being unraveled.

Abstract

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide and Inflammation plays a critical role in the development of CVD. Despite considerable progress in understanding the underlying mechanisms and various treatment options available, significant gaps in therapy necessitate the identification of novel therapeutic targets. Sphingolipids are a family of lipids that have gained attention in recent years as important players in CVDs and the inflammatory processes that underlie their development. As preclinical studies have shown that targeting sphingolipids can modulate inflammation and ameliorate CVDs, targeting sphingolipids has emerged as a promising therapeutic strategy. This review discusses the current understanding of sphingolipids’ involvement in inflammation and cardiovascular diseases, the existing therapeutic approaches and gaps in therapy, and explores the potential of sphingolipids-based drugs as a future avenue for CVD treatment.

Abstract

Abstract: Sphingolipids are essential components of cell membranes and lipoproteins. They are synthesized de novo in the endoplasmic reticulum and subsequently undergo various enzymatic modifications in different organelles, giving rise to a diverse range of biologically active compounds. These molecules play a critical role in regulating cell growth, senescence, migration, apoptosis, and signaling. In recent years, the sphingolipid metabolic pathway has been recognized as a key factor in heart failure (HF) pathophysiology. Abnormal levels of sphingolipid metabolites, such as ceramide (Cer) and sphingomyelin (SM), contribute to oxidative stress and inflammatory responses, ultimately promoting cardiomyocyte apoptosis. Conversely, sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) regulate vascular function and influence cardiac remodeling. Additionally, enzymes such as diacylglycerol acyltransferase 1 (DGAT1) and sphingosine-1-phosphate lyase 1 (SGPL1) modulate cardiac lipid metabolism. Given their role in HF progression, monitoring sphingolipid alterations offers potential as valuable biomarkers for assessing disease severity, prognosis, and diagnosis. Given the complexity of sphingolipid metabolism and its involvement in diverse regulatory biological processes, a comprehensive understanding of its roles at both the cellular and organismal levels in physiopathology remains incomplete. Therefore, this review aims to explore the physiological functions, regulatory mechanisms, and therapeutic potential of sphingolipid metabolism. It will summarize the specific molecular mechanisms driving key pathological processes in HF, including ventricular remodeling, myocardial fibrosis, vascular dysfunction, and metabolic disorders. Finally, the review will highlight targeted sphingolipid metabolites as potential therapeutic strategies, offering new insights into HF diagnosis and treatment, with the goal of advancing adjunctive clinical therapies.

Abstract

Bioactive sphingolipids (SLs) are a category of lipids with sphingoid bases (SB) as their basic backbone structure. These molecules exhibit distinct pharmacological effects by targeting esterases, amidases, kinases, phosphatases, and membrane receptors. The SLs constitute highly complex metabolic pathway interconnections called Sphingolipidome. Each pathway signifies specific subcellular localizations that regulate the functions of SLs. These Sphingolipidome networks control critical functions of the cell involving cell growth by regulating apoptosis, senescence, cell migration, and inflammatory responses. These cellular functions are implicated in cardiovascular diseases, metabolic disorders, neurodegenerative disorders, autoimmune diseases, and cancers. Imbalances in SL metabolic pathways significantly contribute to the development and progression of these diseases. The pharmacological significance of sphingolipids has resulted in several sphingoid-based inhibitors, activators, and modulators for translational drug discovery efforts. Most of these medicinal agents possess close structural similarity with sphingolipids. This review covers the enantioselective syntheses and drug development efforts of sphingolipid-based medicinal agents of preclinical and clinical studies. These agents include Myriocin, Fingolimod, Fenretinide, Safingol, Spisulosine (ES-285), jaspine B, D-e-MAPP, B13, and α-Galactosylceramide. These agents were subjected to molecular modeling studies to understand the binding interactions with the biological target. The rationale discussion of these medicinal agents will help future drug discovery endeavors based on sphingolipid biochemistry.

Abstract

Cardiovascular disease is a leading cause of morbidity and mortality. New research elucidates increasingly complex relationships between cardiac and metabolic health, giving rise to new possible therapeutic targets. Sphingolipids are a heterogeneous class of bioactive lipids with critical roles in normal human physiology. They have also been shown to play both protective and deleterious roles in the pathogenesis of cardiovascular disease. Ceramides are implicated in dysregulating insulin signalling, vascular endothelial function, inflammation, oxidative stress, and lipoprotein aggregation, thereby promoting atherosclerosis and vascular disease. Ceramides also advance myocardial disease by enhancing pathological cardiac remodelling and cardiomyocyte death. Glucosylceramides similarly contribute to insulin resistance and vascular inflammation, thus playing a role in atherogenesis and cardiometabolic dysfunction. Sphingosing-1-phosphate, on the other hand, may ameliorate some of the pathological functions of ceramide by protecting endothelial barrier integrity and promoting cell survival. Sphingosine-1-phosphate is, however, implicated in the development of cardiac fibrosis. This review will explore the roles of sphingolipids in vascular, cardiac, and metabolic pathologies and will evaluate the therapeutic potential in targeting sphingolipids with the aim of prevention and reversal of cardiovascular disease in order to improve long-term cardiovascular outcomes.

Abstract

Eukaryotic organisms as well as some prokaryotes and viruses contain sphingolipids, which are defined by a common structural feature, i.e., a “sphingoid base” backbone such as D-erythro-1,3-dihydroxy, 2-aminooctadec-4-ene (sphingosine). The sphingolipids of mammalian tissues, lipoproteins, and milk include ceramides, sphingomyelins, cerebrosides, gangliosides and sulfatides; plants, fungi and yeast have mainly cerebrosides and phosphoinositides. The total amounts of sphingolipids in food vary considerably, from a few micromoles per kilogram (fruits) to several millimoles per kilogram in rich sources such as dairy products, eggs and soybeans. With the use of the limited data available, per capita sphingolipid consumption in the United States can be estimated to be on the order of 150–180 mmol (∼115–140 g) per year, or 0.3–0.4 g/d. There is no known nutritional requirement for sphingolipids; nonetheless, they are hydrolyzed throughout the gastrointestinal tract to the same categories of metabolites (ceramides and sphingoid bases) that are used by cells to regulate growth, differentiation, apoptosis and other cellular functions. Studies with experimental animals have shown that feeding sphingolipids inhibits colon carcinogenesis, reduces serum LDL cholesterol and elevates HDL, suggesting that sphingolipids represent a “functional” constituent of food. Sphingolipid metabolism can also be modified by constituents of the diet, such as cholesterol, fatty acids and mycotoxins (fumonisins), with consequences for cell regulation and disease. Additional associations among diet, sphingolipids and health are certain to emerge as more is learned about these compounds.

Abstract

Objective

The whole world is still struggling with the COVID-19 pandemic. Inflammation response, thought to be associated with severe illness and death, is an important research topic in COVID-19. Inflammation is also an essential condition explored in psychiatric illnesses. Our knowledge about the relationship between the inflammation response and psychiatric comorbidities in patients with COVID-19 is very limited. In this study, the relationship between anxiety and depression levels and inflammation response of patients with COVID-19 hospitalized in the hospital was examined.

Methods

175 patients were included in the study. Sociodemographic Data Form, Beck Depression Inventory and Beck Anxiety Inventory were applied to the patients. To evaluate the inflammation responses, blood sedimentation rate, C-reactive protein (CRP), procalcitonin, ferritin, neutrophil/lymphocyte ratio (NLR), and IL-6 levels were examined.

Results

In our study, no relationship was found between anxiety and depression levels and inflammatory responses in patients hospitalized with a diagnosis of COVID-19. Anxiety and depression levels of women were higher than men, and NLR, ferritin, IL-6 levels were found to be lower than men. Anxiety levels increase with age. There is a positive correlation between NLR and ferritin levels and duration of hospitalization.

Conclusion

Our study examining the relationship of psychiatric comorbidities with the inflammation response and our increasing literature knowledge, together with studies evaluating the mental effects of COVID-19, suggest that determining the relationship between inflammation responses and psychiatric comorbidities in COVID-19, whose pathophysiology has not been clarified yet, maybe an essential step in interventions on the course of the disease.

Abstract

Sphingolipids, which are components of cellular membranes and organ tissues, can be synthesized or degraded to modulate cellular responses according to environmental cues, and the balance among the different sphingolipids is important for directing immune responses, regardless of whether they originate, as intra- or extracellular immune events. Recent progress in multiomics-based analyses and methodological approaches has revealed that human health and diseases are closely related to the homeostasis of sphingolipid metabolism, and disease-specific alterations in sphingolipids and related enzymes can be prognostic markers of human disease progression. Accumulating human clinical data from genome-wide association studies and preclinical data from disease models provide support for the notion that sphingolipids are the missing pieces that supplement our understanding of immune responses and diseases in which the functions of the involved proteins and nucleotides have been established. In this review, we analyze sphingolipid-related enzymes and reported human diseases to understand the important roles of sphingolipid metabolism. We discuss the defects and alterations in sphingolipid metabolism in human disease, along with functional roles in immune cells. We also introduce several methodological approaches and provide summaries of research on sphingolipid modulators in this review that should be helpful in studying the roles of sphingolipids in preclinical studies for the investigation of experimental and molecular medicines.