Decoding molecular mechanisms:brain aging and Alzheimer's disease

The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions and cognitions,but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders,such as Alzheimer's disease.Beyond these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain.Understanding these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect cognition.This review aims to explore the age-induced changes in brain plasticity and molecular processes,differentiating normal aging from the pathogenesis of Alzheimer's disease,thereby providing insights into predicting the risk of dementia,particularly Alzheimer's disease.

Overview of the immunological mechanisms in hepatitis B virus reactivation:Implications for disease progression and management strategies

Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

Fecal microbiota transplantation for treatment of non-alcoholic fatty liver disease:Mechanism,clinical evidence,and prospect

The population of non-alcoholic fatty liver disease(NAFLD)patients along with relevant advanced liver disease is projected to continue growing,because currently no medications are approved for treatment.Fecal microbiota transplantation(FMT)is believed a novel and promising therapeutic approach based on the concept of the gut-liver axis in liver disease.There has been an increase in the number of pre-clinical and clinical studies evaluating FMT in NAFLD treatment,however,existing findings diverge on its effects.Herein,we briefly summarized the mechanism of FMT for NAFLD treatment,reviewed randomized controlled trials for evaluating its efficacy in NAFLD,and proposed the prospect of future trials on FMT.

Bioactivities,Mechanisms,Production,and Potential Application of Bile Acids in Preventing and Treating Infectious Diseases

Infectious diseases are a global public health problem,with emerging and re-emerging infectious diseases on the rise worldwide.Therefore,their prevention and treatment are still major challenges.Bile acids are common metabolites in both hosts and microorganisms that play a significant role in controlling the metabolism of lipids,glucose,and energy.Bile acids have historically been utilized as first-line,valuable therapeutic agents for related metabolic and hepatobiliary diseases.Notably,bile acids are the major active ingredients of cow bezoar and bear bile,which are commonly used traditional Chinese medicines(TCMs)with the therapeutic effects of clearing heat,detoxification,and relieving wind and spasm.In recent years,the promising performance of bile acids against infectious diseases has attracted attention from the scientific community.This paper reviews for the first time the biological activities,possible mechanisms,production routes,and potential applications of bile acids in the treatment and prevention of infectious diseases.Compared with previous reviews,we comprehensively summarize existing studies on the use of bile acids against infectious diseases caused by pathogenic microorganisms that are leading causes of global morbidity and mortality.In addition,to ensure a stable supply of bile acids at affordable prices,it is necessary to clarify the biosynthesis of bile acids in vivo,which will assist scientists in elucidating the accumulation of bile acids and discovering how to engineer various bile acids by means of chemosynthesis,biosynthesis,and chemoenzymatic synthesis.Finally,we explore the current challenges in the field and recommend a development strategy for bile-acid-based drugs and the sustainable production of bile acids.The presented studies suggest that bile acids are potential novel therapeutic agents for managing infectious diseases and can be artificially synthesized in a sustainable way.

Review on dietary supplements as an effective improvement of Alzheimer's disease:focus on structures and mechanisms

Alzheimer’s disease(AD),the major form of neurodegenerative diseases that can severely impede normal cognitive function,makes it one of the most common fatal diseases.There are currently over 50 million AD patients worldwide.The neuropathology of AD is perplexing and there is a scarcity of disease-modifying treatments.Currently,early diagnosis of AD has been made possible with the discovery of biological markers associated with pathology,providing strong support for the improvement of the disease status.The search for inhibitors of AD markers from dietary supplements(DSs)has become a major hot topic.Especially with the widespread use of DSs,DSs containing polyphenols,alkaloids,terpenes,polysaccharides and other bioactive components can prevent AD by reducing Aβdeposition,inhibiting tau protein hyperphosphorylation,reconstructing synaptic dysfunction,weakening cholinesterase activity,regulating mitochondrial oxidative stress,neuronal inflammation and apoptosis.This review summarizes the anti-AD effects of the main DSs and their bioactive constituents,as well as the potential molecular mechanisms covers from 2017 to 2023.Additionally,we discussed the opportunities and challenges faced by DSs in the process of AD prevention and treatment,aiming to further provide new perspectives for functional food development.

Pathological mechanism of immune disorders in diabetic kidney disease and intervention strategies

Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease.Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes.With the development of immunological technology,many studies have shown that diabetic nephropathy is an immune complex disease,and that most patients have immune dysfunction.However,the immune response associated with diabetic nephropathy and autoimmune kidney disease,or caused by ischemia or infection with acute renal injury,is different,and has a complicated pathological mechanism.In this review,we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism,to provide guidance and advice for early intervention and treatment of diabetic nephropathy.

Bioactive constituents and action mechanism of Xiaoyao San for treatment of non-alcoholic fatty liver disease

Xiaoyao San(XYS)is a classic Chinese medicine prescription.It is traditionally used to relieve syndrome of“liver stagnation and spleen deficiency”,a common syndrome type in traditional Chinese medicine,through soothing liver,tonifying spleen,and nourishing blood.Correspondingly,XYS has long application in the treatment of depression,dyspepsia and liver diseases.Given the rising of cutting-edge researches on XYS,there’s a significant need to diligently uncover the bioactive constituents and action mechanisms of XYS for treating non-alcoholic fatty liver disease accordingly.

Repetitive transcranial magnetic stimulation in Alzheimer’s disease:effects on neural and synaptic rehabilitation

Alzheimer’s disease is a neurodegenerative disease resulting from deficits in synaptic transmission and homeostasis.The Alzheimer’s disease brain tends to be hyperexcitable and hypersynchronized,thereby causing neurodegeneration and ultimately disrupting the operational abilities in daily life,leaving patients incapacitated.Repetitive transcranial magnetic stimulation is a cost-effective,neuro-modulatory technique used for multiple neurological conditions.Over the past two decades,it has been widely used to predict cognitive decline;identify pathophysiological markers;promote neuroplasticity;and assess brain excitability,plasticity,and connectivity.It has also been applied to patients with dementia,because it can yield facilitatory effects on cognition and promote brain recovery after a neurological insult.However,its therapeutic effectiveness at the molecular and synaptic levels has not been elucidated because of a limited number of studies.This study aimed to characterize the neurobiological changes following repetitive transcranial magnetic stimulation treatment,evaluate its effects on synaptic plasticity,and identify the associated mechanisms.This review essentially focuses on changes in the pathology,amyloidogenesis,and clearance pathways,given that amyloid deposition is a major hypothesis in the pathogenesis of Alzheimer’s disease.Apoptotic mechanisms associated with repetitive transcranial magnetic stimulation procedures and different pathways mediating gene transcription,which are closely related to the neural regeneration process,are also highlighted.Finally,we discuss the outcomes of animal studies in which neuroplasticity is modulated and assessed at the structural and functional levels by using repetitive transcranial magnetic stimulation,with the aim to highlight future directions for better clinical translations.

Glucagon-like peptide-1 receptor agonists:Exploring the mechanisms from glycemic control to treatment of multisystemic diseases

This editorial takes a deeper look at the insights provided by Soresi and Giannitrapani,which examined the therapeutic potential of glucagon-like peptide-1 receptor agonists(GLP-1RAs)for metabolic dysfunction-associated fatty liver disease.We provide supplementary insights to their research,highlighting the broader systemic implications of GLP-1RAs,synthesizing the current understanding of their mechanisms and the trajectory of research in this field.GLP-1RAs are revolutionizing the treatment of type 2 diabetes mellitus and beyond.Beyond glycemic control,GLP-1RAs demonstrate cardiovascular and renal protective effects,offering potential in managing diabetic kidney disease alongside renin–angiotensin–aldosterone system inhibitors.Their role in bone metabolism hints at benefits for diabetic osteoporosis,while the neuroprotective properties of GLP-1RAs show promise in Alzheimer's disease treatment by modulating neuronal insulin signaling.Additionally,they improve hormonal and metabolic profiles in polycystic ovary syndrome.This editorial highlights the multifaceted mechanisms of GLP-1RAs,emphasizing the need for ongoing research to fully realize their therapeutic potential across a range of multisystemic diseases.

Computational and bioinformatics tools for understanding disease mechanisms

Computational methods have significantly transformed biomedical research,offering a comprehensive exploration of disease mechanisms and molecular protein functions.This article reviews a spectrum of computational tools and network analysis databases that play a crucial role in identifying potential interactions and signaling networks contributing to the onset of disease states.The utilization of protein/gene interaction and genetic variation databases,coupled with pathway analysis can facilitate the identification of potential drug targets.By bridging the gap between molecular-level information and disease understanding,this review contributes insights into the impactful utilization of computational methods,paving the way for targeted interventions and therapeutic advancements in biomedical research.

Effect of Dietary Resistant Starch on Prevention and Treatment of Obesity-related Diseases and Its Possible Mechanisms

Overweight or obesity has become a serious public health problem in the world, scientists are concentrating their efforts on exploring novel ways to treat obesity. Nowadays, the availabilities of bariatric surgery and pharmacotherapy have enhanced obesity treatment, but it should has support from diet, physical exercise and lifestyle modification, especially the functional food. Resistant starch, an indigestible starch, has been studied for years for its beneficial effects on regulating blood glucose level and lipid metabolism. The aim of this review is to summarize the effect of resistant starch on weight loss and the possible mechanisms. According to numerous previous studies it could be concluded that resistant starch can reduce fat accumulation, enhance insulin sensitivity, regulate blood glucose level and lipid metabolism. Recent investigations have focused on the possible associations between resistant starch and incretins as well as gut microbiota. Resistant starch seems to be a promising dietary fiber for the prevention or treatment of obesity and its related diseases.

Neurofibrillary tangles in Alzheimer＇s disease： elucidation of the molecular mechanism by immunohistochemistry and tau protein phospho-proteomics

As a key contributor to memory storage, the synapse is one of the earliest affected neuronal components in Alzheimer＇s disease （AD）. Under physiological conditions, the synaptic con- nections between neurons undergo activity-dependent func- tional and morphological re-organisation. This dynamic, ＇plastic＇ neural ability critically depends on the structural integrity of the synapse. Thus, proteins that are implicated in preserving the organisation and dynamics of synaptic connections, including microtubules of the cytoskeleton and associated proteins, have attracted much focus for their involvement in the malfunction- ing AD synapse.

Effect of Body Mass Index on All-cause Mortality and Incidence of Cardiovascular Diseases─Report for Meta-Analysis of Prospective Studies on Optimal Cut-off Points of Body Mass Index in Chinese Adults

Objective To verify the optimal cut-off points for overweight and obesity in Chinese adults based on the relationship of baseline body mass index (BMI) to all-cause mortality, and incidence of cardiovascular diseases from pooled data of Chinese cohorts. Methods The prospective study data of existing cohort studies in China were collected, and the age-adjusted all-cause mortality stratified by BMI were estimated. The similar analysis was repeated after excluding deaths within the first three years of follow-up and after excluding smokers. The incidence of age-adjusted coronary heart disease (CHD) and stroke stratified by BMI were also analyzed. Multiple Cox regression coefficients of BMI for the incidence of CHD and stroke after controlling other risk factors were pooled utilizing the methods of weighting by inverse of variance to reveal whether BMI had independent effect and its strength on the incidence of CHD and stroke. Results The data of 4 cohorts including 76 227 persons, with 745 346 person-years of follow-up were collected and analyzed. The age-adjusted all-cause mortality stratified by BMI showed a U-shaped curve, even after excluding deaths within the first three years of follow-up and excluding smokers. Age-adjusted all-cause mortality increased when BMI was lower than 18.5 and higher than 28. The incidence of CHD and stroke, especially ishemic stroke increased with increasing BMI, this was consistent with parallel increasing of risk factors. Cox regression analysis showed that BMI was an independent risk factor for both CHD and stroke. Each amount of 2 kg/m2 increase in baseline BMI might cause 15.4%, 6.1% and 18.8 % increase in relative risk of CHD, total stroke and ischemic stroke. Reduction of BMI to under 24 might prevent the incidence of CHD by 11% and that of stroke by 15 % for men, and 22 % of both diseases for women. Conclusion BMI ≤18.5, 24-27.9 and ≥28 (kg/m2) is the appropriate cut-off points for underweight, overweight and obesity in Chinese adults.

Adverse Effects of Inactivated Foot-and-Mouth Disease Vaccine—Possible Causes Analysis and Countermeasures

Foot-and-mouth disease (FMD) is an infectious and sometimes fatal viral disease that affects cloven-hoofed animals, and Chinese government adopts compulsory immunization measures for FMD. The adverse effects of FMD vaccine to pigs, cattle and goats have been reported increasingly frequent during the spring and autumn seasons when large numbers of farm livestock are vaccinated. The financial losses caused by vaccine adverse effects have been a serious concern for both farmers and primary prevention personnel. There are various causative factors reported to involve into adverse effect of FMD vaccine, including the inappropriate vaccine production, transportation and storage, livestock poor tolerance, and unqualified vaccinating manipulations. Symptomatic treatment and early drug prevention have a certain effect on the adverse effects. To analyze causes and propose countermeasures, in the current study possible reasons during the production and processing procedures of inactivated FMD vaccine were reviewed and corresponding countermeasures were recommended. The review may provide references for better use of vaccine to prevent FMD.

Mechanisms of Huanglian Jiedu Decoction in treating coronary heart disease and type 2 diabetes mellitus based on network pharmacology

Objective:To explore the common mechanism of Huanglian Jiedu Decoction in treating coronary heart disease and type 2 diabetes by network pharmacology.Methods:All chemical components and targets of the four drugs in Huanglian Jiedu Decoction were retrieved through TCMSP,and the genes were standardized through Uniprot database.Acquire disease targets related to coronary heart disease and diabetes in OMIM and GeneCards databases.The network diagram of"drug-component-target-disease"is constructed by using the software of cytopscape 3.7.2,the PPI network diagram of protein interaction is constructed by using STRING database,and the network diagram of"drug-disease"core target is constructed by using the software of cytopscape 3.7.2.DAVID's online database platform was used to analyze GO biological process and KEGG pathway enrichment of common targets of Huanglian Jiedu Decoction in treating coronary heart disease and type 2 diabetes.Results:103 active ingredients of Huanglian Jiedu Decoction were retrieved,including 140 acting targets,5342 coronary heart disease targets,114 diabetes targets,and 14 common intersection targets of drugs and diseases,involving AR,PPARG,TNF,IL6,CCL2,VEGFA,PON1,etc.The GO biological process analysis results in 98 biological processes,10 cell components and 10 molecular functions.Among them are positive regulation of gene expression,positive regulation of nitric oxide biosynthesis process,Extracellular space,cytokine activity,steroid hormone receptor activity and other biological processes;The enrichment analysis of KEGG pathway yielded 20 signal pathways(P≤0.05).It mainly involves Malaria,cancer in cancer,HIF-1 signaling pathway,TNF signaling pathway,NOD-like receptor signaling pathway,PI3K-Akt signaling pathway,etc.Conclusion:Huanglian Jiedu Decoction"treats different diseases at the same time"coronary heart disease and type 2 diabetes have the characteristics of multiple components,multiple targets and multiple pathways,which provide theoretical basis for Huanglian Jiedu Decoction to treat coronary heart disease and type 2 diabetes in clinic,but the key targets and pathways of Huanglian Jiedu Decoction to treat diseases still need further experimental verification.

Mechanism and Application of Plant Rhizospheric Bacillus sp. for Growth Promotion and Disease Prevention

In order to promote the development and application of environmental-friendly,efficient and safe beneficial Bacillus sp.preparations,the paper summarizes and systematically elaborates the colonization of Bacillus sp.in host plants and the mechanism of synergistic effect on disease prevention of host plants,further reviews the application of rhizospheric Bacillus sp.in promoting the growth of agricultural and forestry crops and controlling plant diseases,and prospects the scientific issues and application of plant rhizospheric Bacillus sp.in the future.

Research progress on effective chemical constituents of Sijunzi Decoction and mechanism of prevention and treatment of digestive system diseases

Sijunzi Decoction,as one of the classic Chinese traditional prescriptions,has been used clinically by major physicians since the Song Dynasty.This article reviewed and sorted out the literature on the effective chemistry of Sijunzi Decoction and the mechanism of its prevention and treatment of digestive system diseases.At present,its effective chemical components are derived from the saponins and flavonoids in ginseng and licorice,and are effective for gastrointestinal mucosal injury diseases and malignant digestive system.Digestive system diseases such as tumors,functional gastrointestinal diseases,non-alcoholic fatty liver,acute liver injury,and liver failure show a multi-path,multi-target effect mechanism.This article reviews the effective chemical components and research of Sijunzi Decoction and the related mechanisms of prevention and treatment of digestive system diseases,and provides valuable clues for the follow-up research of Sijunzi Decoction.

Melastatin-related transient receptor potential 2 channel in Aβ_(42)-induced neuroinflammation: implications to Alzheimer's disease mechanism and development of therapeutics

Alzheimer’s disease （AD） is an age-related eurodegenerative disease that represents the most common cause of dementia among the elderly people. With the increasingly aging population, AD has presented an overwhelming healthcare challenge to modern society; the World Alzheimer Report 2015 has estimated that 46.8 million people worldwide lived with dementia in 2015 and this number will rise to 74.7 million in 2030 and that the total cost of dementia was 818 billion in US$ in 2015 and will reach two trillion in 2030. Post-mortem studies have identified two histopathological hallmarks in the brains of AD patients; extracellular senile plaque with elevated deposition of amyloid β （Aβ） peptides, and intracellular neurofibrillary tangle composed of hyper-phosphorylated microtubule-associated protein tau.Etiologically, progressive neuronal loss within the cerebral cortex and hippocampus regions of the brain leads to irreversible decline in, and eventually complete loss of, memory and other cognitive functions that afflict AD patients. The widely-accepted amyloid cascade hypothesis for AD pathogenesis holds that accumulation and aggregation of neurotoxic Aβ peptides, due to imbalance of their generation and clearance as a result of changes in genetic makeup, aging and/or exposure to environmental risk factors, is a major and early trigger of AD. This hypothesis has continuously gained support by preclinical and clinical studies （Selkoe and Hardy, 2016）. However, the intensive and costly drug discovery efforts over the past decades based on such a hypothesis have proved extremely frustrating in developing effective therapeutics to treat or slow down the progress of AD, highlighting the need for more research to improve our understanding towards the cellular and molecular mechanisms by which Aβ peptides bring about neurotoxicity and cognitive dysfunction.

Role of ferroptosis in Parkinson’s disease and intervention mechanism of acupuncture and moxibustion

Parkinson’s disease(PD)is the second neurodegenerative disease in the world.The pathological characteristics of PD are degeneration,loss and death of dopaminergic neurons in the substantia nigra of the midbrain.At present,most scholars believe that the main pathogenesis of PD is α-synuclein aggregation,oxidative stress,mitochondrial dysfunction and neuroinflammatory reaction.More and more studies have demonstrated that ferroptosis plays an important role in the occurrence and development of PD.Ferroptosis is a new type of cell death that is significantly different from traditional apoptosis,scorching and necrosis.Its main feature is iron-dependent lipid peroxidation.Some studies have found that the efficacy of acupuncture and moxibustion in the treatment of PD may be related to the regulation of ferroptosis.Therefore,this study mainly discusses the occurrence and development mechanism of ferroptosis and its role in PD,and the possible mechanism of acupuncture and moxibustion in the treatment of PD dopaminergic neurons,so as to provide theoretical basis for acupuncture and moxibustion in the treatment of PD.

Influence of Underlying Diseases and Age on the Association between Obesity and All-Cause Mortality in Post-Middle Age

Background: Studies on the association between obesity and all-cause mortality have found that the degree of obesity is directly proportional to all-cause mortality. In contrast, there have been studies indicating that obese people with underlying diseases have a higher survival rate. We hypothesized that age and underlying diseases lead to such contrasting results. Therefore, we conducted a study to clarify the influence of post-middle age obesity and underlying diseases on all-cause mortality. Methods: This study used data from longitudinal studies in the United States, which conducted follow-up for 19 years on 33,708 participants in different age groups: ≥45, 45 - 64, and ≥65 years. Hazard ratio (HR) was determined using the Cox proportional hazards model to analyze a group consisting of all participants, a group of those with underlying diseases, and a group of those without underlying diseases, considering age, gender, education history, marital status, household income, smoking history, and BMI category as covariates. Results: In the group aged ≥65 without underlying diseases, HR was almost 1 in those with BMI 25 - 35 kg/m2. Further, HR was higher in the 45 - 64 age group without underlying diseases if BMI was >35 kg/m2. However, HR was approximately 1 in the ≥65 age group. Conclusions: The study revealed that among individuals aged ≥65 years without underlying diseases, there was no association between obesity and all-cause mortality. Among individuals without underlying diseases, HR was higher in the 45 - 64 age group with BMI > 35 kg/m2 but was approximately 1 among those aged ≥65 years. Therefore, an interaction based on age was detected. These findings may lead to recommendations regarding the need to modify the advice and education provided to obese individuals in different age groups.