Treatment Of Various Chronic Diseases Research Articles

Mini-Review: Tregs as a Tool for Therapy—Obvious and Non-Obvious Challenges and Solutions

Tregs have the potential to be utilized as a novel therapeutic agent for the treatment of various chronic diseases, including diabetes, Alzheimer’s disease, asthma, and rheumatoid arthritis. One of the challenges associated with developing a therapeutic product based on Tregs is the non-selectivity of polyclonal cells. A potential solution to this issue is a generation of antigen-specific CAR-Tregs. Other challenges associated with developing a therapeutic product based on Tregs include the phenotypic instability of these cells in an inflammatory microenvironment, discrepancies between engineered Treg-like cells and natural Tregs, and the expression of dysfunctional isoforms of Treg marker genes. This review presents a summary of proposed strategies for addressing these challenges.

Germacrone: A Multi-targeting Sesquiterpene with Promising Anti-cancer and Chronic Disease Applications.

Germacrone, a naturally occurring active compound found in essential oils extracted from medicinal plants within the Zingiberaceae family, has garnered attention for its potential therapeutic applications. Extensive research has highlighted its multi-targeting capabilities, positioning it as a promising treatment for various chronic diseases, including cancer, cardiovascular conditions, and neurodegenerative disorders like Alzheimer's disease. This review aims to provide a comprehensive overview of germacrone as a scaffold for developing multi-targeting drugs with therapeutic potential against a range of chronic disorders. The study delves into the molecular mechanisms that underlie the therapeutic effects of germacrone and explores its potential targets, including NF-κB, PI3K/AKT/mTOR, p53, JAK/STAT, caspase, apoptosis, and autophagy induction. A systematic review of literature databases was conducted to gather relevant studies on germacrone and its therapeutic applications. The molecular mechanisms and potential targets of germacrone were examined to elucidate its multi-targeting capabilities. Germacrone exhibits significant potential in the management of chronic diseases, with demonstrated effects on various cellular pathways. The review highlights its impact on NF-κB, PI3K/AKT/mTOR, p53, JAK/STAT, caspase, apoptosis, and autophagy induction, showcasing its versatility in targeting multiple pathways associated with chronic conditions. Germacrone has emerged as a promising candidate for the treatment of diverse chronic diseases. The understanding of its multi-targeting capabilities, coupled with its natural origin, positions it as a valuable scaffold for developing therapeutics. The exploration of germacrone as a structural framework for multi-targeting drugs offers a potential avenue to enhance efficacy while minimizing potential side effects. Further research and clinical trials are warranted to validate the therapeutic potential of germacrone in diverse medical contexts.

Mechanistic study on the alleviation of postmenopausal osteoporosis by Lactobacillus acidophilus through butyrate-mediated inhibition of osteoclast activity

In China, traditional medications for osteoporosis have significant side effects, low compliance, and high costs, making it urgent to explore new treatment options. Probiotics have demonstrated superiority in the treatment of various chronic diseases, and the reduction of bone mass in postmenopausal osteoporosis (PMOP) is closely related to the degradation and metabolism of intestinal probiotics. It is crucial to explore the role and molecular mechanisms of probiotics in alleviating PMOP through their metabolites, as well as their therapeutic effects. We aim to identify key probiotics and their metabolites that affect bone loss in PMOP through 16srDNA sequencing combined with non-targeted metabolomics sequencing, and explore the impact and possible mechanisms of key probiotics and their metabolites on the progression of PMOP in the context of osteoporosis caused by estrogen deficiency. The sequencing results showed a significant decrease in Lactobacillus acidophilus and butyrate in PMOP patients. In vivo experiments confirmed that the intervention of L. acidophilus and butyrate significantly inhibited osteoclast formation and bone resorption activity, improved intestinal barrier permeability, suppressed B cells, and the production of RANKL on B cells, effectively reduced systemic bone loss induced by oophorectomy, with butyric acid levels regulated by L. acidophilus. Consistently, in vitro experiments have confirmed that butyrate can directly inhibit the formation of osteoclasts and bone resorption activity. The above research results indicate that there are various pathways through which L. acidophilus inhibits osteoclast formation and bone resorption activity through butyrate. Intervention with L. acidophilus may be a safe and promising treatment strategy for osteoclast related bone diseases, such as PMOP.

Improvement of the Thermal Stability and Aqueous Solubility of Three Matrine Salts Assembled by the Similar Structure Salt Formers.

Matrine (MAT), a natural Chinese herbal medicine, has a unique advantage in the treatment of various chronic diseases. However, its low melting point, low bioavailability, and high dosage restrict its subsequent development into new drugs. In this study, three kinds of MAT salts, namely, MAT-2,5-dihydroxybenzoic acid (MAT-25DHB), MAT-2,6-dihydroxybenzoic acid (MAT-26DHB), and MAT-salicylic acid-hydrate (MAT-SAL-H2O), were designed and synthesized to improve the drugability of MAT. The three salts were characterized by using various analytical techniques, including single-crystal X-ray diffractometry, powder X-ray diffractometry, differential scanning calorimetry, thermogravimetry, and infrared spectroscopy. The results of the thermal stability evaluation showed that the formation of salts improved the stability of MAT; MAT-25DHB is the most stable salt reported at present. The results of aqueous solubility showed that the solubility of MAT-25DHB was higher than that of MAT, while that of MAT-26DHB and MAT-SAL-H2O were less. Given that the MAT-25DHB salt further improved the solubility of MAT, it is expected to be subjected to further research as an optimized salt. Lattice energy and solvation free energy are important factors affecting the solubility of salts; the reasons for the changes of solubility and stability of three kinds of salts are explained by calculating them.

Study on the solid-liquid equilibrium and thermodynamic model of the L-phenylalanine + L-tryptophan + water system.

Amino acids hold significant importance in the diagnosis and treatment of various chronic diseases. Accurate solid-liquid equilibrium data are the key to drug synthesis and chemical production. However, the studies on the solid-liquid equilibrium of amino acids remain limited. In this work, the solid-liquid equilibrium of the L-tryptophan + L-phenylalanine + water ternary system under atmospheric pressure at temperatures of 278.15 K-318.15 K was explored via isothermal solution saturation. The isothermal equilibrium phase diagram of the ternary system was constructed. The obtained solid-liquid equilibrium data were correlated with a semi-empirical-model, yielding thermodynamic parameters pa, pb, pc, and k. Furthermore, the model can be used to effectively predict the solid-liquid equilibrium data of ternary systems at other temperatures, and the dY and dP are 0.005 and 4.34%, respectively. The solid-liquid equilibrium data and ternary equilibrium phase diagrams of the system were utilized for the separation and purification of an L-tryptophan and L-phenylalanine mixture. By employing thermodynamic models to calculate the relevant phase diagram data for mixtures with different proportions, effective separation and purification of the mixture could be achieved using the principles of variable temperature phase diagrams. These works are valuable for optimizing chemical processes and have practical implications in the field.

Probiotic: is diet part of the efficacy equation?

ABSTRACT Discovered at the beginning of the 20th century by Nobel laureate Élie Metchnikoff, probiotics have more recently emerged as a potential noninvasive therapeutic approach for the treatment of various chronic diseases. However, recent population-based clinical studies suggest that probiotics are often ineffective and may even exhibit potential deleterious effects. Hence, a deeper molecular understanding of strain-specific beneficial effects, together with the identification of endogenous/exogenous factors modulating probiotic efficacy, is needed. The lack of consistency in probiotic efficacy, together with the observation that numerous preclinical findings on probiotics are not translating once applied to humans through clinical trials, suggests a central role for environmental factors, such as dietary patterns, in probiotic efficacy. Two recent studies have been instrumental in filling this knowledge gap, defining the role played by diet in probiotic efficacy on metabolic deregulations in both mouse models and humans .

Structural insights into interactions of new polymeric (μ–oxo) bridged Cu(II) complexes of taurine with yeast tRNA by spectroscopic and computational approaches and its application towards chemoresistant cancer lines

RNA-targeted drugs are considered as safe treatment option for the cure of many chronic diseases preventing off-targeted delivery and acute toxic manifestations. FDA has approved many such RNA therapies in different phases of clinical trials, validating their use for the treatment of various chronic diseases. We report herein, new water-soluble (μ–oxo) bridged polymeric Cu(II) complexes of taurine (2–aminoethane sulfonic acid) complexes 1 and 2. The therapeutic potency of 1 and 2 was ascertained by studying biophysical interactions with tRNA/ct-DNA. The experimental results demonstrated that the complexes interacted avidly to nucleic acids through intercalation mode depicting a specific preference for tRNA in comparison to ct–DNA and, moreover 2 showed higher binding propensity than 1. The electrophoretic behaviour of the complexes with plasmid pBR322 DNA and tRNA were examined by gel mobility assay that revealed a concentration-dependent activity with complex 2 performing more efficient cleavage as compared to complex 1. Cytotoxicity results on cancer cell strains displayed higher cytotoxicity than complex 1 against treated cancer cells. The synthesized copper(II) taurine complexes have met the basic criteria of anticancer drug design as they are structurally well-characterized, exhibiting good solubility in water, lipophilic in nature with superior intercalating propensity towards tRNA and cytotoxic in nature.

Role of Turmeric and Curcumin in Prevention and Treatment of Chronic Diseases: Lessons Learned from Clinical Trials.

Turmeric (Curcuma longa) has been used for thousands of years for the prevention and treatment of various chronic diseases. Curcumin is just one of >200 ingredients in turmeric. Almost 7000 scientific papers on turmeric and almost 20,000 on curcumin have been published in PubMed. Scientific reports based on cell culture or animal studies are often not reproducible in humans. Therefore, human clinical trials are the best indicators for the prevention and treatment of a disease using a given agent/drug. Herein, we conducted an extensive literature survey on PubMed and Scopus following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The keywords "turmeric and clinical trials" and "curcumin and clinical trials" were considered for data mining. A total of 148 references were found to be relevant for the key term "turmeric and clinical trials", of which 70 were common in both PubMed and Scopus, 44 were unique to PubMed, and 34 were unique to Scopus. Similarly, for the search term "curcumin and clinical trials", 440 references were found to be relevant, of which 70 were unique to PubMed, 110 were unique to Scopus, and 260 were common to both databases. These studies show that the golden spice has enormous health and medicinal benefits for humans. This Review will extract and summarize the lessons learned about turmeric and curcumin in the prevention and treatment of chronic diseases based on clinical trials.

Lentiviral overexpression of VEGFC in transplanted MSCs leads to resolution of swelling in a mouse tail lymphedema model.

Dysfunction of the lymphatic system following injury, disease, or cancer treatment can lead to lymphedema, a debilitating condition with no cure. Despite the various physical therapy and surgical options available, most treatments are palliative and fail to address the underlying lymphatic vascular insufficiency driving lymphedema progression. Stem cell therapy provides a promising alternative in the treatment of various chronic diseases with a wide range of therapeutic effects that reduce inflammation, fibrosis, and oxidative stress, while promoting lymphatic vessel (LV) regeneration. Specifically, stem cell transplantation is suggested to promote LV restoration, rebuild lymphatic circulation, and thus potentially be utilized towards an effective lymphedema treatment. In addition to stem cells, studies have proposed the administration of vascular endothelial growth factor C (VEGFC) to promote lymphangiogenesis and decrease swelling in lymphedema. Here, we seek to combine the benefits of stem cell therapy, which provides a cellular therapeutic approach that can respond to the tissue environment, and VEGFC administration to restore lymphatic drainage. Specifically, we engineered mesenchymal stem cells (MSCs) to overexpress VEGFC using a lentiviral vector (hVEGFC MSC) and investigated their therapeutic efficacy in improving LV function and tissue swelling using near infrared (NIR) imaging, and lymphatic regeneration in a single LV ligation mouse tail lymphedema model. First, we showed that overexpression of VEGFC using lentiviral transduction led to an increase in VEGFC protein synthesis in vitro. Then, we demonstrated hVEGFC MSC administration post-injury significantly increased the lymphatic contraction frequency 14-, 21-, and 28-days post-surgery compared to the control animals (MSC administration) in vivo, while also reducing tail swelling 28-days post-surgery compared to controls. Our results suggest a therapeutic potential of hVEGFC MSC in alleviating the lymphatic dysfunction observed during lymphedema progression after secondary injury and could provide a promising approach to enhancing autologous cell therapy for treating lymphedema.

Amalgamation of Nanoparticles within Drug Carriers: A Synergistic Approach or a Futile Attempt?

In recent years, nanotechnology has gained much attention from scientists and significant advances in therapeutic potential. Nano-delivery systems have emerged as an effective way in order to improve the therapeutic properties of drugs including solubility, stability, prolongation of half-life as well as promoting the accumulation of drug at the target site. The nanoparticles have also been incorporated into various conventional drug delivery systems. This review study aims to introduce the amalgamation of nanoparticles into drug carriers. To overcome the limitations of single nanoparticles such as toxicity, high instability, rapid drug release as well as limited drug loading capacity, a multi-component system is developed. Liposomes, microparticles, nanofibers, dendrimers etc., are promising drug carriers, having some limitations that can be minimized, and the compilation of nanoparticles synergizes the properties. The amalgamated nanocarriers are used for the diagnostic purpose as well as treatment of various chronic diseases. It also increases the solubility of hydrophobic drugs. However, each system has its advantages and disadvantages based on its physicochemical properties, efficacy, and other parameters. This review details the past and present state of development for the fusion of nanoparticles within drug carriers and from which we identify future research works needed for the same.

Chronic Disease Prediction Using Machine Learning

Abstract: Technological advancement, including machine learning, has a significant impact on health by allowing for more accurate diagnosis and treatment of various chronic diseases. Accurate prediction is critical in the biomedical and healthcare communities for determining the risk of disease in patients. The only way to overcome chronic disease mortality is to predict it earlier so that disease prevention can be implemented. Such a model is a Patient's requirement for which Machine Learning is highly recommended. However, a doctor finds it difficult to make an exact forecast based just on symptoms. The most challenging task is making an accurate diagnosis of a disease. Data mining is crucial in helping to predict the sickness and solve this issue. Based on a dataset for chronic diseases from the UCI machine learning data warehouse, this study assesses chronic diseases using machine learning techniques. In order to create accurate prediction models for various chronic diseases using data mining approaches, we employ datasets for heart disease, kidney disease, cancer disease, and diabetes disease. To increase accuracy and shorten training time, the dataset's most pertinent features are chosen. The system evaluates the user's symptoms as input and outputs the likelihood that the disease will occur. The implementation of Logistic Regression is used to predict disease. Prediction of diseases like diabetes, heart disease, cancer, and kidney disease using logistic regression, random forest, and decision trees are performed. Different models, methodologies, and algorithms are utilized to forecast and analyses each chronic disease. The study includes a conceptual model that includes the prediction of the majority of chronic diseases.

Isolation of Bioactive Compounds from Fruit Body of Lentinula edodes (Berk.) Pegler and In Silico Approach using Tyrosinase Target Protein Involved in Melanin Production

Traditionally, Lentinula edodes are used in many Asian countries for the treatment of various chronic diseases. In the current study, ethyl acetate fraction of fruit body of Lentinula edodes was obtained by standard bioassay-guided fractionation procedure. This fractionation resulted in the isolation of three bioactive compounds (compound 1 already reported, compound 2 and 3 first time reported from this mushroom) and their structures were characterized using various spectroscopic techniques. Further, all the compounds were studied using molecular docking analysis. Compounds 1, 2, 3 and standard active ingredient used for the treatment of hyperpigmentation i.e. arbutin was prepared as program database files, was docked with the target receptor (tyrosinase, program database ID: 5M8L) which plays a vital role in melanogenesis pathway. The study mainly focuses on better results of compounds as potent tyrosinase inhibitors to down-regulate the melanogenesis pathway. The present study revealed that due to the presence of compound 1 and 3 in the fruit body of Lentinula edodes, it may be preferred as a cosmetic product in extract form to obtain effective skin lightening properties or treatment of melisma. Compounds 2 and 3 was first isolated from Lentinula edodes. The study further concludes that compound 3 could act as a potential lead molecule for the target gene tyrosinase with slight modification or optimization of chemical structure to obtain more effective, less toxic lead molecule and further exhibits remarkable skin lightening properties via inhibiting melanin production.

Ongoing and potential novel trends of pomegranate fruit peel; a comprehensive review of its health benefits and future perspectives as nutraceutical.

Pomegranate is an ancient shrub, globally distributed nowadays. It has been used in the middle east as a medicinal food and traditional medicine for thousands of years. Pomegranate peel (PP) constitutes about 50% of the total fruit, however, it has been previously regarded as a waste. Recent research points to PP as a rich source of phenolics (e.g., ellagitannins, flavonoids, and anthocyanins), polysaccharides, in addition to its biotransformed metabolites viz. urolithins making it a valuable waste with promising pharmacological actions. Compared to the pulp and the juice, PP exhibited stronger antioxidant and antimicrobial activities. Besides, it inhibited inflammation in several conditions, including colitis, arthritis, hepatitis, contact dermatitis, and lung inflammation. Moreover, it displayed anti-osteoporosis, anti-hyperglycemic, antidiabetic, antihypertensive, vasculoprotective, hepatoprotective, neuroprotective, and immunomodulatory effects. Additionally, it was effective as a prebiotic and in obesity control, besides it promoted wound healing. Furthermore, PP demonstrated anticancer effects against different cancer types, for example, colon, liver, thyroid, uterine, breast, bladder, prostate, leukemia, and osteosarcoma. Despite PP safety, it may interfere with the metabolism of other drugs because it inhibits cytochromes (CYP) changing their bioavailability, effectiveness, and toxicity. PP biowaste valorization not only avoids against its environmental and economic burden but can also provide a promising platform to produce novel or improved nutraceuticals. This study provides a comprehensive overview of PP biological activities with the reported action mechanisms related to its phytochemicals and further biotransformed metabolites inside the body. Future research prospects to unravel the merits of such waste and optimize its use are discussed. PRACTICAL APPLICATION: Pomegranate is widely distributed throughout the world. Although its peel was previously considered a waste, recent research regards it as a rich source of bioactive compounds with promising biological activities. Its recycling not only overcomes the bio-waste problems, but also provides a source of valuable compounds with several health benefits. In recent years, PP has been demonstrated to exhibit excellent pharmacological bioactivities, for example, antioxidant, anti-inflammatory, antimicrobial, antiosteoporosis, antihyperlipidemic, and anticancer activities. Its health-promoting power is mostly attributed to the phenolic and polysaccharide content, in addition to its amazing biotransformed metabolites. The underlying action mechanisms of such pharmacological activities are discussed and related to its chemical content. This review presents the latest research progress on the role of PP in the prevention and treatment of various chronic diseases, and its protective health effects for future research to be used in nutraceuticals.

Embelin: A novel XIAP inhibitor for the prevention and treatment of chronic diseases.

Chronic diseases are a serious health concern worldwide, especially in the elderly population. Most chronic diseases like cancer, cardiovascular ailments, neurodegenerative disorders, and autoimmune diseases are caused due to the abnormal functioning of multiple signaling pathways that give rise to critical anomalies in the body. Although a lot of advanced therapies are available, these have failed to entirely cure the disease due to their less efficacy. Apart from this, they have been shown to manifest disturbing side effects which hamper the patient's quality of life to the extreme. Since the last few decades, extensive studies have been done on natural herbs due to their excellent medicinal benefits. Components present in natural herbs target multiple signaling pathways involved in diseases and therefore hold high potential in the prevention and treatment of various chronic diseases. Embelin, a benzoquinone, is one such agent isolated from Embelia ribes, which has shown excellent biological activities toward several chronic ailments by upregulating a number of antioxidant enzymes (e.g., SOD, CAT, GSH, etc.), inhibiting anti-apoptotic genes (e.g., TRAIL, XIAP, survivin, etc.), modulating transcription factors (e.g., NF-κB, STAT3, etc.) blocking inflammatory biomarkers (e.g., NO, IL-1β, IL-6, TNF-α, etc.), monitoring cell cycle synchronizing genes (e.g., p53, cyclins, CDKs, etc.), and so forth. Several preclinical studies have confirmed its excellent therapeutic activities against malicious diseases like cancer, obesity, heart diseases, Alzheimer's, and so forth. This review presents an overview of embelin, its therapeutic prospective, and the molecular targets in different chronic diseases.

Efficacy of Tai Chi on Patients With Chronic Kidney Disease.

Previous systematic reviews elucidate the efficacy of Tai Chi on the rehabilitation and treatment for various chronic diseases. Yet, no consensus has been reached on its efficacy and safety from those with chronic kidney disease (CKD). Therefore, we conducted a systematic review to critically summarize what is already known about the prevailing benefits of Tai Chi for CKD patients. There was no evidence that Tai Chi had adverse effects on CKD patients. Long-term Tai Chi exercises could improve quality of life, cardiorespiratory fitness, and physical motor function for the end-stage renal disease (ERSD) patients undergoing dialysis. Regular Tai Chi exercises might exert modest influences in delaying CKD progression for mild-moderate CKD patients. However, there is insufficient evidence to demonstrate positive effects of Tai Chi exercises on bone health of the ESRD patients. Accordingly, rigorously designed, longer-term studies of Tai Chi are warranted to identify its efficacy on CKD patients across different stages, especially targeting potential mechanisms in terms of Tai Chi altering biological gene profile expressions.

Recent progress in preparation of microcapsules with tailored structures for bio-medical applications

Nature is continuously giving us a wide variety of molecules with a great therapeutic potential that are able to fulfill protection, in humans, from anticancer and antibacterial to antioxidant or anti-inflammatory. Unfortunately, almost all plant-derived biomolecules have a low physiological stability, reduced bioavailability, a prolonged circulation time in the blood, or non-selectivity regarding the target tissue. Furthermore, the oral administration of plant-derived biomolecules proved not to be always efficient, only if high doses are applied. Lately, a lot of effort is given to find novel technologies to provide them protection till the target site is reached, by their entrapment inside a properly engineered system.Current review is focused on the existent microencapsulation technologies of plant-derived bioactive compounds, offering details about main steps of the fabrication processes used to obtain a high encapsulation efficiency. A special attention was offered to specific cellular uptake, intracellular localization and transport of micro delivery systems, but also to their therapeutic potential that could be a promising approach for the treatment of various chronic diseases. An outlook into future research on novel microcapsules for biomedical and pharmaceutical applications is also provided.

Current clinical developments in curcumin-based therapeutics for cancer and chronic diseases.

The last decade has seen an unprecedented rise in the prevalence of chronic diseases worldwide. Different mono-targeted approaches have been devised to treat these multigenic diseases, still most of them suffer from limited success due to the off-target debilitating side effects and their inability to target multiple pathways. Hence a safe, efficacious, and multi-targeted approach is the need for the hour to circumvent these challenging chronic diseases. Curcumin, a natural compound extracted from the rhizomes of Curcuma longa, has been under intense scrutiny for its wide medicinal and biological properties. Curcumin is known to manifest antibacterial, antiinflammatory, antioxidant, antifungal, antineoplastic, antifungal, and proapoptotic effects. A plethora of literature has already established the immense promise of curcuminoids in the treatment and clinical management of various chronic diseases like cancer, cardiovascular, metabolic, neurological, inflammatory, and infectious diseases. To date, more than 230 clinical trials have opened investigations to understand the pharmacological aspects of curcumin in human systems. Still, further randomized clinical studies in different ethnic populations warrant its transition to a marketed drug. This review summarizes the results from different clinical trials of curcumin-based therapeutics in the prevention and treatment of various chronic diseases.

Towards chemotherapy of tuberculosis: experiments with external use of copper salts in lupus

The question of the treatment of various chronic diseases, especially tuberculosis, with drugs with chemotherapeutic properties, has long been in the focus of attention of researchers. Chemotherapy seeks mainly to influence the body with certain medicinal substances, which, while destroying _ pathogens, do not harm the body itself.

Hydroxychloroquine induces oxidative DNA damage and mutation in mammalian cells

Since the early stages of the pandemic, hydroxychloroquine (HCQ), a widely used drug with good safety profile in clinic, has come to the forefront of research on drug repurposing for COVID-19 treatment/prevention. Despite the decades-long use of HCQ in the treatment of diseases, such as malaria and autoimmune disorders, the exact mechanisms of action of this drug are only beginning to be understood. To date, no data are available on the genotoxic potential of HCQ in vitro or in vivo. The present study is the first investigation of the DNA damaging- and mutagenic effects of HCQ in mammalian cells in vitro, at concentrations that are comparable to clinically achievable doses in patient populations. We demonstrate significant induction of a representative oxidative DNA damage (8-oxodG) in primary mouse embryonic fibroblasts (MEFs) treated with HCQ at 5 and 25 μM concentrations (P = 0.020 and P = 0.029, respectively), as determined by enzyme-linked immunosorbent assay. Furthermore, we show significant mutagenicity of HCQ, manifest as 2.2- and 1.8-fold increases in relative cII mutant frequency in primary and spontaneously immortalized Big Blue® MEFs, respectively, treated with 25 μM dose of this drug (P = 0.005 and P = 0.012, respectively). The observed genotoxic effects of HCQ in vitro, achievable at clinically relevant doses, are novel and important, and may have significant implications for safety monitoring in patient populations. Given the substantial number of the world’s population receiving HCQ for the treatment of various chronic diseases or in the context of clinical trials for COVID-19, our findings warrant further investigations into the biological consequences of therapeutic/preventive use of this drug.

The Effects of Medicinal Plants and Bioactive Natural Compounds on Homocysteine.

Background: Among non-communicable diseases, cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity in global communities. By 2030, CVD-related deaths are projected to reach a global rise of 25 million. Obesity, smoking, alcohol, hyperlipidemia, hypertension, and hyperhomocysteinemia are several known risk factors for CVDs. Elevated homocysteine is tightly related to CVDs through multiple mechanisms, including inflammation of the vascular endothelium. The strategies for appropriate management of CVDs are constantly evolving; medicinal plants have received remarkable attention in recent researches, since these natural products have promising effects on the prevention and treatment of various chronic diseases. The effects of nutraceuticals and herbal products on CVD/dyslipidemia have been previously studied. However, to our knowledge, the association between herbal bioactive compounds and homocysteine has not been reviewed in details. Thus, the main objective of this study is to review the efficacy of bioactive natural compounds on homocysteine levels according to clinical trials and animal studies. Results: Based on animal studies, black and green tea, cinnamon, resveratrol, curcumin, garlic extract, ginger, and soy significantly reduced the homocysteine levels. According to the clinical trials, curcumin and resveratrol showed favorable effects on serum homocysteine. In conclusion, this review highlighted the beneficial effects of medicinal plants as natural, inexpensive, and accessible agents on homocysteine levels based on animal studies. Nevertheless, the results of the clinical trials were not uniform, suggesting that more well-designed trials are warranted.