Myrtus communis leaves: source of bio - actives, traditional use, their biological properties, and prospects / Hojas de Myrtus communis: fuente de bioactivos, uso tradicional, sus propiedades biológicas y perspectivas

Myrtus communis L., commonly known as true myrtle, is a medicinal plant native to the Mediterranean area. Since ancient times, the inhabitant s of this area have been using it for its cultural and medicinal properties. Because of the vast diversity of biomolecules in its aerial parts, it exhibits several biological properties, including antioxidant, antimicrobial, and anticancer properties. This review retrospect the research on the source, biological activities with empirical evidence, chemical composition, applications, and cellular targets of extracts and essential oils obtained from M. communis leaves, which provides a perspective for further studies on the applications and formulations of extract and EO of M. communis leaves. The efficacy of constituents' individually, in association with other bioactive constituents, or in combination with available commercial drugs would provide insights in to the development of these bio - actives as future drugs and their evolving future potential applications in the pharmaceutical, food, and aroma industries.

Myrtus communis L., comúnmente conocido como arrayán verdadero, es una planta medicinal originaria de la zona mediterránea. Desde la antigüedad, los habitantes de esta zona lo utilizan por sus propiedades culturales y medicinales. Debido a la gran div ersidad de biomoléculas en sus partes aéreas, exhibe varias propiedades biológicas, incluidas propiedades antioxidantes, antimicrobianas y anticancerígenas. Esta revisión retrospectiva de la investigación sobre la fuente, las actividades biológicas con evi dencia empírica, la composición química, las aplicaciones y los objetivos celulares de los extractos y aceites esenciales obtenidos de las hojas de M. communis , lo que brinda una perspectiva para futuros estudios sobre las aplicaciones y formulaciones de l os extractos y EO de M. communis . La eficacia de los componentes individualmente, en asociación con otros componentes bioactivos o en combinación con medicamentos comerciales disponibles proporcionaría información sobre el desarrollo de estos bioactivos co mo medicamentos futuros y sus futuras aplicaciones potenciales en las industrias farmacéutica, alimentaria y aromática

Artemisinin and its derivatives as promising therapies for autoimmune diseases.

Artemisinin, a traditional Chinese medicine with remarkable antimalarial activity. In recent years, studies demonstrated that artemisinin and its derivatives (ARTs) showed anti-inflammatory and immunoregulatory effects. ARTs have been developed and gradually applied to treat autoimmune and inflammatory diseases. However, their role in the treament of patients with autoimmune and inflammatory diseases in particular is less well recognized. This review will briefly describe the history of ARTs use in patients with autoimmune and inflammatory diseases, the theorized mechanisms of action of the agents ARTs, their efficacy in patients with autoinmmune and inflammatory diseases. Overall, ARTs have numerous beneficial effects in patients with autoimmune and inflammatory diseases, and have a good safety profile.

Ginsenoside Rg3: A Review of its Anticancer Mechanisms and Potential Therapeutic Applications.

BACKGROUND: Traditional Chinese Medicine (TCM) has a long history of treating various diseases and is increasingly being recognized as a complementary therapy for cancer. A promising natural compound extracted from the Chinese herb ginseng is ginsenoside Rg3, which has demonstrated significant anticancer effects. It has been tested in a variety of cancers and tumors and has proven to be effective in suppressing cancer. OBJECTIVES: This work covers various aspects of the role of ginsenoside Rg3 in cancer treatment, including its biological functions, key pathways, epigenetics, and potential for combination therapies, all of which have been extensively researched and elucidated. The study aims to provide a reference for future research on ginsenoside Rg3 as an anticancer agent and a support for the potential application of ginsenoside Rg3 in cancer treatment.

Induction of Autophagy by Extract from Corydalis heterocarpa for Skin Anti-Aging.

The extracts of Corydalis heterocarpa, a salt-tolerant plant, exhibit diverse physiological properties, including anti-inflammatory, anticancer, and antiadipogenic effects. However, the anti-aging effects of C. heterocarpa extract (CHE) on human skin cells have not yet been investigated. In the present study, we determined that CHE inhibited senescence-associated ß-galactosidase (SA-ß-gal)-stained senescent human dermal fibroblasts (HDFs). Furthermore, CHE markedly suppressed the expression of major regulatory proteins involved in senescence, including p53, p21, and caveolin-1. Interestingly, CHE promoted autophagic flux, as confirmed by the formation of microtubule-associated protein 1 light chain 3B (LC3B) puncta and lysosomal activity. Notably, using RNA sequencing (RNA-seq), we showed that CHE selectively regulated the gene expression of leucine-rich repeat and sterile alpha motif-containing 1 (LRSAM1), an important regulator of autophagy. The adenosine-monophosphate activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway, which is essential for autophagy regulation, was also modulated by CHE. LRSAM1 depletion not only inhibited LC3B expression but also decreased the autophagy flux induced by CHE. Moreover, the knockdown of LRSAM1 suppressed the reversal of CHE-induced senescence in old HDFs. Collectively, our study has revealed the rejuvenating effects and molecular mechanisms of CHE, suggesting that CHE may be a promising anti-aging agent.

Traumatic Brain Injury Recovery with Photobiomodulation: Cellular Mechanisms, Clinical Evidence, and Future Potential.

Traumatic Brain Injury (TBI) remains a significant global health challenge, lacking effective pharmacological treatments. This shortcoming is attributed to TBI's heterogeneous and complex pathophysiology, which includes axonal damage, mitochondrial dysfunction, oxidative stress, and persistent neuroinflammation. The objective of this study is to analyze transcranial photobiomodulation (PBM), which employs specific red to near-infrared light wavelengths to modulate brain functions, as a promising therapy to address TBI's complex pathophysiology in a single intervention. This study reviews the feasibility of this therapy, firstly by synthesizing PBM's cellular mechanisms with each identified TBI's pathophysiological aspect. The outcomes in human clinical studies are then reviewed. The findings support PBM's potential for treating TBI, notwithstanding variations in parameters such as wavelength, power density, dose, light source positioning, and pulse frequencies. Emerging data indicate that each of these parameters plays a role in the outcomes. Additionally, new research into PBM's effects on the electrical properties and polymerization dynamics of neuronal microstructures, like microtubules and tubulins, provides insights for future parameter optimization. In summary, transcranial PBM represents a multifaceted therapeutic intervention for TBI with vast potential which may be fulfilled by optimizing the parameters. Future research should investigate optimizing these parameters, which is possible by incorporating artificial intelligence.

Ginsenosides from Panax ginseng as potential therapeutic candidates for the treatment of inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is characterized by a chronic inflammation of the intestine, which significantly affects patients' quality of life. As a perennial plant with the homology of medicine and food, Panax ginseng is known for its substantial anti-inflammatory effects in various inflammatory disorders. Ginsenosides, the main bioactive compounds of P. ginseng, are recognized for their efficacy in ameliorating inflammation. PURPOSE: Over the past decade, approximately 150 studies have investigated the effects of P. ginseng and ginsenosides on IBD treatment and new issues have arisen. However, there has yet to be a comprehensive review assessing the potential roles of ginsenosides in IBD therapy. METHOD: This manuscript strictly adheres to the PRISMA guidelines, thereby guaranteeing systematic synthesis of data. The research articles referenced were sourced from major scientific databases, including Google Scholar, PubMed, and Web of Science. The search strategy employed keywords such as "ginsenoside", "IBD", "colitis", "UC", "inflammation", "gut microbiota", and "intestinal barrier". For image creation, Figdraw 2.0 was methodically employed. RESULTS: Treatment with various ginsenosides markedly alleviated clinical IBD symptoms. These compounds have been observed to restore intestinal epithelia, modulate cellular immunity, regulate gut microbiota, and suppress inflammatory signaling pathways. CONCLUSION: An increasing body of research supports the potential of ginsenosides in treating IBD. Ginsenosides have emerged as promising therapeutic agents for IBD, attributed to their remarkable efficacy, safety, and absence of side effects. Nevertheless, their limited bioavailability presents a substantial challenge. Thus, efforts to enhance the bioavailability of ginsenosides represent a crucial and promising direction for future IBD research.

Characterisation of new in vitro models and identification of potentially active drugs in angiosarcoma.

Angiosarcoma is a rare soft tissue sarcoma originating from endothelial cells. Given that current treatments for advanced disease have shown limited efficacy, alternative therapies need to be identified. In rare diseases, patient-derived cell models are crucial for screening anti-tumour activity. In this study, cell line models were characterised in 2D and 3D cultures. The cell lines' growth, migration and invasion capabilities were explored, confirming them as useful tools for preclinical angiosarcoma studies. By screening a drug library, we identified potentially effective compounds: 8-amino adenosine impacted cell growth and inhibited migration and invasion at considerably low concentrations as a single agent. No synergistic effect was detected when combining with paclitaxel, gemcitabine or doxorubicin. These results suggest that this compound could be a potentially useful drug in the treatment of AGS.

Review of advanced practice nurse role in infection throughout the hematopoietic stem cell transplant journey.

BACKGROUND: Prolonged periods of immunosuppression during hematopoietic stem cell transplant (HSCT) can result in serious infectious complications and contribute to transplant-related morbidity and mortality. Adherence to standardized pre and postinfection screening guidelines, prescribed medications, and early identification of infectious symptoms through comprehensive patient and family education are crucial to minimizing infectious complications. Advanced practice nurses (APNs) are key members of the multidisciplinary care team in the HSCT specialty, maintaining a specialized skillset and scope of practice which includes a holistic based, preventative medicine and risk mitigation approach. METHODS: This review sought to describe the role of the APN in HSCT care and to further examine existing APN led models of care which focus on infection prevention and education throughout the HSCT treatment journey. RESULTS: No studies specifically examined the APN role in infectious diseases risk assessment, screening, and management throughout the HSCT journey were identified throughout our review, however, there was considerable evidence to demonstrate the benefits of APN led care in the oncology and solid organ transplantation specialty which led to improvements in continuity of care, overall patient outcomes, and multidisciplinary team collaboration. The key themes identified in our review, were the role of the APN in the delivery of comprehensive patient and family education, the role of the APN in supporting, mentoring, and educating junior medical and nursing teams, the collaboration between the APN and the multidisciplinary care team, and the role of the APN in prompt recognition, triage, and management of treatment related complications, such as infection.

Lycium barbarum polysaccharide's protective effects against PM2.5-induced cellular senescence in HUVECs.

Fine particulate matter (PM2.5) exposure is strongly associated with vascular endothelial senescence, a process implicated in cardiovascular diseases. While there is existing knowledge on the impact of Lycium barbarum polysaccharide (LBP) on vascular endothelial damage, the protective mechanism of LBP against PM2.5-induced vascular endothelial senescence remains unclear. In this study, we investigated the impact of PM2.5 exposure on vascular endothelial senescence and explored the intervention effects of LBP in human umbilical vein endothelial cells (HUVECs). We found that PM2.5 exposure dose-dependently reduced cell viability and proliferation in HUVECs while increasing the production of reactive oxygen species (ROS), malondialdehyde (MDA), and hydrogen peroxide (H2O2). Additionally, PM2.5 exposure inhibited the activity of superoxide dismutase (SOD). Notably, PM2.5 exposure induced autophagy impairments and cellular senescence. However, LBP mitigated PM2.5-induced cell damage. Further studies demonstrated that correcting autophagy impairment in HUVECs reduced the expression of the senescence markers P16 and P21 induced by PM2.5. This suggests the regulatory role of autophagy in cellular senescence and the potential of LBP in improving HUVECs senescence. These findings provide novel insights into the mechanisms underlying PM2.5-induced cardiovascular toxicity and highlight the potential of LBP as a therapeutic agent for improving vascular endothelial health.

Therapeutic effect of dietary ingredients on cellular senescence in animals and humans: A systematic review.

BACKGROUND: Cellular senescence has been regarded as a therapeutic target for ageing and age-related diseases. Several senotherapeutic agents have been proposed, including compounds derived from natural products which hold the translational potential to promote healthy ageing. This systematic review examined the association of dietary ingredients with cellular senescence in animals and humans, with an intent to identify dietary ingredients with senotherapeutic potential. METHODS: This systematic review was registered at PROSPERO International prospective register of systematic reviews (Reg #: CRD42022338885). The databases PubMed and Embase were systematically searched for key terms related to cellular senescence, senescence markers, diets, nutrients and bioactive compounds. Intervention and observational studies on human and animals investigating the effects of dietary ingredients via oral administration on cellular senescence load were included. The SYRCLE's risk of bias tool and Cochrane risk of bias tool v2.0 were used to assess the risk of bias for animal and human studies respectively. RESULTS: Out of 5707 identified articles, 83 articles consisting of 78 animal studies and 5 human studies aimed to reduce cellular senescence load using dietary ingredients. In animal studies, the most-frequently used senescence model was normative ageing (26 studies), followed by D-galactose-induced models (17 studies). Resveratrol (8 studies), vitamin E (4 studies) and soy protein isolate (3 studies) showed positive effects on reducing the level of senescence markers such as p53, p21, p16 and senescence-associated ß-galactosidase in various tissues of physiological systems. In three out of five human studies, ginsenoside Rg1 had no positive effect on reducing senescence in muscle tissues after exercise. The risk of bias for both animal and human studies was largely unclear. CONCLUSION: Resveratrol, vitamin E and soy protein isolate are promising senotherapeutics studied in animal models. Studies testing dietary ingredients with senotherapeutic potential in humans are limited and translation is highly warranted.

Selenium Compounds Affect Differently the Cytoplasmic Thiol/Disulfide State in Dermic Fibroblasts and Improve Cell Migration by Interacting with the Extracellular Matrix.

Deficient wound healing is frequently observed in patients diagnosed with diabetes, a clinical complication that compromises mobility and leads to limb amputation, decreasing patient autonomy and family lifestyle. Fibroblasts are crucial for secreting the extracellular matrix (ECM) to pave the wound site for endothelial and keratinocyte regeneration. The biosynthetic pathways involved in collagen production and crosslinking are intimately related to fibroblast redox homeostasis. In this study, two sets of human dermic fibroblasts were cultured in normal (5 mM) and high (25 mM)-glucose conditions in the presence of 1 µM selenium, as sodium selenite (inorganic) and the two selenium amino acids (organic), Se-cysteine and Se-methionine, for ten days. We investigated the ultrastructural changes in the secreted ECM induced by these conditions using scanning electron microscopy (SEM). In addition, we evaluated the redox impact of these three compounds by measuring the basal state and real-time responses of the thiol-based HyPer biosensor expressed in the cytoplasm of these fibroblasts. Our results indicate that selenium compound supplementation pushed the redox equilibrium towards a more oxidative tone in both sets of fibroblasts, and this effect was independent of the type of selenium. The kinetic analysis of biosensor responses allowed us to identify Se-cysteine as the only compound that simultaneously improved the sensitivity to oxidative stimuli and augmented the disulfide bond reduction rate in high-glucose-cultured fibroblasts. The redox response profiles showed no clear association with the ultrastructural changes observed in matrix fibers secreted by selenium-treated fibroblasts. However, we found that selenium supplementation improved the ECM secreted by high-glucose-cultured fibroblasts according to endothelial migration assessed with a wound healing assay. Direct application of sodium selenite and Se-cysteine on purified collagen fibers subjected to glycation also improved cellular migration, suggesting that these selenium compounds avoid the undesired effect of glycation.

Characterization of Nanohybridosomes from Lipids and Spruce Homogenate Containing Extracellular Vesicles.

Introduction: Lipid nanovesicles associated with bioactive phytochemicals from spruce needle homogenate (here called nano-sized hybridosomes or nanohybridosomes, NSHs) were considered. Methods: We formed NSHs by mixing appropriate amounts of lecithin, glycerol and supernatant of isolation of extracellular vesicles from spruce needle homogenate. We visualized NSHs by light microscopy and cryogenic transmission electron microscopy and assessed them by flow cytometry, dynamic light scattering, ultraviolet-visual spectroscopy, interferometric light microscopy and liquid chromatography-mass spectrometry. Results: We found that the particles consisted of a bilayer membrane and a fluid-like interior. Flow cytometry and interferometric light microscopy measurements showed that the majority of the particles were nano-sized. Dynamic light scattering and interferometric light microscopy measurements agreed well on the average hydrodynamic radius of the particles Rh (between 140 and 180 nm), while the concentrations of the particles were in the range between 1013 and 1014/mL indicating that NSHs present a considerable (more than 25%) of the sample which is much more than the yield of natural extracellular vesicles (EVs) from spruce needle homogenate (estimated less than 1%). Spruce specific lipids and proteins were found in hybridosomes. Discussion: Simple and low-cost preparation method, non-demanding saving process and efficient formation procedure suggest that large-scale production of NSHs from lipids and spruce needle homogenate is feasible.

A study of the biological effects of low-level light.

Low-level light therapy (LLLT), also known as photo biomodulation (PBM), is a type of optical therapy that uses red or near-infrared lasers or light-emitting diodes (LEDs) for medical treatment. The laser wavelengths involved in PBM typically range between 600-700 nm and 780-1100 nm, with power densities ranging between 5 mW/cm2 and 5 W/cm2. PBM is a series of biochemical cascades exhibited by biological tissues after absorbing a certain amount of energy from light. PBM has been widely used in clinical practice in the past 20 years, and numerous clinical trials have demonstrated its biological efficacy. However, the underlying mechanisms have not yet been fully explored. In this paper, we have summarized the research into PBM over the past two decades, to identify the important mechanisms of the biological effects of PBM from the perspective of molecular mechanisms, cellular levels, and tissue changes. We hope our study provide a theoretical basis for future investigations into the underlying mechanisms.

A computational tumor growth model experience based on molecular dynamics point of view using deep cellular automata.

Cancer, as identified by the World Health Organization, stands as the second leading cause of death globally. Its intricate nature makes it challenging to study solely based on biological knowledge, often leading to expensive research endeavors. While tremendous strides have been made in understanding cancer, gaps remain, especially in predicting tumor behavior across various stages. The integration of artificial intelligence in oncology research has accelerated our insights into tumor behavior, right from its genesis to metastasis. Nevertheless, there's a pressing need for a holistic understanding of the interactions between cancer cells, their microenvironment, and their subsequent interplay with the broader body environment. In this landscape, deep learning emerges as a potent tool with its multifaceted applications in diverse scientific challenges. Motivated by this, our study presents a novel approach to modeling cancer tumor growth from a molecular dynamics' perspective, harnessing the capabilities of deep-learning cellular automata. This not only facilitates a microscopic examination of tumor behavior and growth but also delves deeper into its overarching behavioral patterns. Our work primarily focused on evaluating the developed tumor growth model through the proposed network, followed by a rigorous compatibility check with traditional mathematical tumor growth models using R and Matlab software. The outcomes notably aligned with the Gompertz growth model, accentuating the robustness of our approach. Our validated model stands out by offering adaptability to diverse tumor growth datasets, positioning itself as a valuable tool for predictions and further research.

Engineered macrophage-derived cellular vesicles for NIR-II fluorescence imaging-guided precise cancer photo-immunotherapy.

Significant progress has been made in cancer immunotherapy; however, challenges such as interpatient variability, limited treatment response, and severe side effects persist. Although nanoimmunotherapy has emerged as a promising approach, the construction of precise and efficient nanosystems remain formidable challenges. Herein, a multifunctional nanoplatform was developed using macrophage-derived cellular vesicles (MCVs) for NIR-II imaging-guided precise cancer photo-immunotherapy. MCVs exhibited excellent tumor targeting and TAMs re-education effects, serving as both delivery carriers and therapeutic agents. Through amide bond, indocyanine green (ICG) was conjugated to the surface of MCVs, enabling in vivo tracking of MCVs distribution. Notably, ICG exhibited dual functionality as a NIR-II fluorescent agent and possessed photodynamic and photothermal effects, enabling the conversion of light energy into chemical or heat energy to eliminate tumor cells. This precision phototherapy triggered immunogenic cell death (ICD) of tumor, thereby activating the anti-tumor immune response. Additionally, MCVs loaded with R848, a toll-like receptor agonist, augmented the ICD-induced anti-tumor immunity. Animal experiments confirmed that MCVs-mediated photoimmunotherapy promoted T cell infiltration, inhibited tumor growth, and improved survival rates. In conclusion, we have developed a promising precision immunotherapy strategy capable of enhancing the immune response while mitigating off-target effects. These findings offer encouraging prospects for clinical translation.

Uptake and cellular responses of Microcystis aeruginosa to PFOS in various environmental conditions.

Although PFOS has been banned as a persistent organic pollutant, it still exists in large quantities within the environment, thus impacting the health of aquatic ecosystems. Previous studies focused solely on high PFOS concentrations, disregarding the connection with environmental factors. To gain a more comprehensive understanding of the PFOS effects on aquatic ecosystems amidst changing environmental conditions, this study investigated the cellular responses of Microcystis aeruginosa to varying PFOS concentrations under heatwave and nutrient stress conditions. The results showed that PFOS concentrations exceeding 5.0 µg/L had obvious effects on multiple physiological responses of M. aeruginosa, resulting in the suppression of algal cell growth and the induction of oxidative damage. However, PFOS concentration at levels below 20.0 µg/L has been found to enhance the growth of algal cells and trigger significant oxidative damage under heatwave conditions. Heatwave conditions could enhance the uptake of PFOS in algal cells, potentially leading to heightened algal growth when PFOS concentration was equal to or less than 5.0 µg/L. Conversely, deficiency or limitation of nitrogen and phosphorus significantly decreased algal abundance and chlorophyll content, inducing severe oxidative stress that could be mitigated by exposure to PFOS. This study holds significance in managing the impact of PFOS on algal growth across diverse environmental conditions.

Resveratrol-loaded invasome gel: A promising nanoformulation for treatment of skin cancer.

Skin cancer is a widespread type of cancer representing 30% of all cancer types worldwide. Resveratrol (RSV) is an anticancer drug used for skin cancer treatment. Several limitations of RSV such as poor aqueous solubility, first-pass metabolism, and instability limit their topical use. The study aimed to develop and optimize RSV-loaded invasomes for topical administration as well as assess their efficacy in vivo. The optimized RSV-loaded invasomes showed small particle size (208.7 ± 74 nm), PDI (0.3 ± 0.03), high % entrapment efficiency (77.7 ± 6%), and negative zeta potential (-70.4 ± 10.9 mV). They showed an initial burst effect followed by controlled drug release for 24 h. RSV-loaded invasomal gel revealed the highest skin deposition percentage (65%) in ex vivo rat skin, the highest potency (low IC50 of 6.34 µg/mL), and the highest cellular uptake when tested on squamous cancerous cells (SCCs) when compared to other formulations. The antitumor effect of topical RSV-loaded invasomes was also evaluated in vivo in Ehrlich-induced mice models. The results revealed that RSV-loaded invasomal gel exhibited the smallest tumor volume with no signs of organ toxicity indicating its safety in skin cancer treatment. Upregulation of BAX and Caspase-3 gene levels and downregulation of NF-kB and BCL2 protein levels were demonstrated using RT-PCR and ELISA tests, respectively. Interestingly, the present study is the first to develop RSV-loaded invasomal gel for topical skin cancer treatment. According to our results, invasomes are considered promising lipid-based nanosystems for topical RSV delivery having high skin penetration ability and anticancer effect in the treatment of skin carcinoma.

Durability of humoral and cellular immunity six months after the BNT162b2 bivalent booster.

Studies about the duration of the humoral and cellular response following the bivalent booster administration are still scarce. We aimed at assessing the humoral and cellular response in a cohort of healthcare workers that received this booster. Blood samples were collected before the administration of the bivalent booster from Pfizer-BioNTech and after 14, 28, 90, and 180 days. Neutralizing antibodies against either the D614G strain, the delta variant, the BA.5 variant, or the XBB.1.5 subvariant were measured. The cellular response was assessed by measurement of the release of interferon gamma from T cells in response to an in vitro SARS-CoV-2 stimulation. A substantial waning of neutralizing antibodies was observed after 6 months (23.1-fold decrease), especially considering the XBB.1.5 subvariant. The estimated T1/2 of neutralizing antibodies was 16.1 days (95% CI = 10.2-38.4 days). Although most participants still present a robust cellular response after 6 months (i.e., 95%), a significant decrease was also observed compared to the peak response (0.95 vs. 0.41 UI/L, p = 0.0083). A significant waning of the humoral and cellular response was observed after 6 months. These data can also help competent national authorities in their recommendation regarding the administration of an additional booster.

Vitamin B12 Deficiency and the Nervous System: Beyond Metabolic Decompensation-Comparing Biological Models and Gaining New Insights into Molecular and Cellular Mechanisms.

Vitamin B12 (VitB12) is a micronutrient and acts as a cofactor for fundamental biochemical reactions: the synthesis of succinyl-CoA from methylmalonyl-CoA and biotin, and the synthesis of methionine from folic acid and homocysteine. VitB12 deficiency can determine a wide range of diseases, including nervous system impairments. Although clinical evidence shows a direct role of VitB12 in neuronal homeostasis, the molecular mechanisms are yet to be characterized in depth. Earlier investigations focused on exploring the biochemical shifts resulting from a deficiency in the function of VitB12 as a coenzyme, while more recent studies propose a broader mechanism, encompassing changes at the molecular/cellular levels. Here, we explore existing study models employed to investigate the role of VitB12 in the nervous system, including the challenges inherent in replicating deficiency/supplementation in experimental settings. Moreover, we discuss the potential biochemical alterations and ensuing mechanisms that might be modified at the molecular/cellular level (such as epigenetic modifications or changes in lysosomal activity). We also address the role of VitB12 deficiency in initiating processes that contribute to nervous system deterioration, including ROS accumulation, inflammation, and demyelination. Consequently, a complex biological landscape emerges, requiring further investigative efforts to grasp the intricacies involved and identify potential therapeutic targets.

Heavy Metal Exposure: Molecular Pathways, Clinical Implications, and Protective Strategies.

Heavy metals are often found in soil and can contaminate drinking water, posing a serious threat to human health. Molecular pathways and curation therapies for mitigating heavy metal toxicity have been studied for a long time. Recent studies on oxidative stress and aging have shown that the molecular foundation of cellular damage caused by heavy metals, namely, apoptosis, endoplasmic reticulum stress, and mitochondrial stress, share the same pathways as those involved in cellular senescence and aging. In recent aging studies, many types of heavy metal exposures have been used in both cellular and animal aging models. Chelation therapy is a traditional treatment for heavy metal toxicity. However, recently, various antioxidants have been found to be effective in treating heavy metal-induced damage, shifting the research focus to investigating the interplay between antioxidants and heavy metals. In this review, we introduce the molecular basis of heavy metal-induced cellular damage and its relationship with aging, summarize its clinical implications, and discuss antioxidants and other agents with protective effects against heavy metal damage.