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.

Molecular mechanisms of aflatoxin neurotoxicity and potential neuroprotective agents

Aflatoxins(AFTs)represent one of the most notorious classes of deadly mycotoxins produced by certain fungi that are found on agricultural crops.Aflatoxins are highly toxic to mammals and are known to cause a series of detrimental effects,including neuro-,hepato-,nephron-,and immuno-toxicity.In this original review we summarize the mechanisms of aflatoxin-induced neurotoxicity and the clinical potential of novel neuroprotective agents.Aflatoxin B1(AFB1)is the most toxic congener among the 21 identified AFTs.Recent studies have shown that food borne exposure to AFB1 and/or its metabolites often leads to fatal neurotoxicity in animals and humans.Animal studies indicated that AFB1 exposure could induce abnormal behavioral changes,including anxiety,lethargy disorders,depression-like behavior,cognitive,learning and memory defects,and decreased feeding behavior.Mechanistically,AFB1 exposure has been associated with lipid peroxidation,ablation of non-enzymatic and enzymatic antioxidant defense systems and decreased neurotransmitter levels.AFB1 exposure has also been shown to induce DNA damage,apoptosis,pyroptosis,and mitochondrial dysfunction in the brain tissue.Several signaling pathways,including gasdermin D,toll like receptor 2(TLR2),TLR4,Akt,NF-κB,ERK/MAPK,protein kinase C(PKC),and mitochondrial apoptotic pathways have been shown to participate in AFB1-induced neuronal or astrocyte cell death.Targeting these pathways by small molecules(e.g.,quercetin,curcumin,and gallic acid,and dimethyl fumarate),Chinese herbal extracts(e.g.,Artichoke leaf extract,Chelidonium majus ethanolic extract,pumpkin extract,and Crocus sativus L.tea),and probiotic supplements could effectively improve AFB1-induced neurobehavioral abnormalities and neurotoxicity.To date,the precise molecular mechanisms of AFB1-induced neurotoxicity and potential neuroprotective agents remain unclear.In the present review,the clinical manifestations,molecular mechanisms,and potential neuroprotective agents of AFB1-induced neurotoxicity are summarized in the broadest overview.It is most hopeful that this broad reaching review provides valuable insights and stimulates broader discussion to develop the effective neuroprotective agents against aflatoxins.

Dysregulated microRNAs in type 2 diabetes and breast cancer:Potential associated molecular mechanisms

Type 2 diabetes(T2D)is a multifaceted and heterogeneous syndrome associated with complications such as hypertension,coronary artery disease,and notably,breast cancer(BC).The connection between T2D and BC is established through processes that involve insulin resistance,inflammation and other factors.Despite this comprehension the specific cellular and molecular mechanisms linking T2D to BC,especially through microRNAs(miRNAs),remain elusive.miRNAs are regulators of gene expression at the post-transcriptional level and have the function of regulating target genes by modulating various signaling pathways and biological processes.However,the signaling pathways and biological processes regulated by miRNAs that are associated with T2D and BC have not yet been elucidated.This review aims to identify dysregulated miRNAs in both T2D and BC,exploring potential signaling pathways and biological processes that collectively contribute to the development of BC.

Seed Storability in Rice: Physiological Foundations, Molecular Mechanisms, and Applications in Breeding

Long-term storage of crop seeds is critical for the conservation of germplasm resources, ensuring food supply, and supporting sustainable production. Rice, as a major food staple, has a substantial stock for consumption and production worldwide. However, its food value and seed viability tend to decline during storage. Understanding the physiological responses and molecular mechanisms of aging tolerance forms the basis for enhancing seed storability in rice. This review outlines the latest progress in influential factors, evaluation methods, and identification indices of seed storability. It also discusses the physiological consequences, molecular mechanisms, and strategies for breeding aging-tolerant rice in detail. Finally, it highlights challenges in seed storability research that require future attention. This review offers a theoretical foundation and research direction for uncovering the mechanisms behind seed storability and breeding aging-tolerant rice.

Classification of musical hallucinations and the characters along with neural-molecular mechanisms of musical hallucinations associated with psychiatric disorders

BACKGROUND Musical hallucinations(MH)involve the false perception of music in the absence of external stimuli which links with different etiologies.The pathomechanisms of MH encompass various conditions.The etiological classification of MH is of particular importance and offers valuable insights to understand MH,and further to develop the effective treatment of MH.Over the recent decades,more MH cases have been reported,revealing newly identified medical and psychiatric causes of MH.Functional imaging studies reveal that MH activates a wide array of brain regions.An up-to-date analysis on MH,especially on MH comorbid psychiatric conditions is warranted.AIM To propose a new classification of MH;to study the age and gender differences of MH in mental disorders;and neuropathology of MH.METHODS Literatures searches were conducted using keywords such as“music hallucination,”“music hallucination and mental illness,”“music hallucination and gender difference,”and“music hallucination and psychiatric disease”in the databases of PubMed,Google Scholar,and Web of Science.MH cases were collected and categorized based on their etiologies.The t-test and ANOVA were employed(P<0.05)to compare the age differences of MH different etiological groups.Function neuroimaging studies of neural networks regulating MH and their possible molecular mechanisms were discussed.RESULTS Among the 357 yielded publications,294 MH cases were collected.The average age of MH cases was 67.9 years,with a predominance of females(66.8%females vs 33.2%males).MH was classified into eight groups based on their etiological mechanisms.Statistical analysis of MH cases indicates varying associations with psychiatric diagnoses.CONCLUSION We carried out a more comprehensive review of MH studies.For the first time according to our knowledge,we demonstrated the psychiatric conditions linked and/or associated with MH from statistical,biological and molecular point of view.

Molecular mechanisms underlying the neuroprotection of environmental enrichment in Parkinson’s disease

Parkinson’s disease is the most common movement disorder,affecting about 1%of the population over the age of 60 years.Parkinson’s disease is characterized clinically by resting tremor,bradykinesia,rigidity and postural instability,as a result of the progressive loss of nigrostriatal dopaminergic neurons.In addition to this neuronal cell loss,Parkinson’s disease is characterized by the accumulation of intracellular protein aggregates,Lewy bodies and Lewy neurites,composed primarily of the proteinα-synuclein.Although it was first described almost 200 years ago,there are no disease-modifying drugs to treat patients with Parkinson’s disease.In addition to conventional therapies,non-pharmacological treatment strategies are under investigation in patients and animal models of neurodegenerative disorders.Among such strategies,environmental enrichment,comprising physical exercise,cognitive stimulus,and social interactions,has been assessed in preclinical models of Parkinson’s disease.Environmental enrichment can cause structural and functional changes in the brain and promote neurogenesis and dendritic growth by modifying gene expression,enhancing the expression of neurotrophic factors and modulating neurotransmission.In this review article,we focus on the current knowledge about the molecular mechanisms underlying environmental enrichment neuroprotection in Parkinson’s disease,highlighting its influence on the dopaminergic,cholinergic,glutamatergic and GABAergic systems,as well as the involvement of neurotrophic factors.We describe experimental pre-clinical data showing how environmental enrichment can act as a modulator in a neurochemical and behavioral context in different animal models of Parkinson’s disease,highlighting the potential of environmental enrichment as an additional strategy in the management and prevention of this complex disease.

Insight into the liver dysfunction in COVID-19 patients: Molecular mechanisms and possible therapeutic strategies

As of June 2022,more than 530 million people worldwide have become ill with coronavirus disease 2019(COVID-19).Although COVID-19 is most commonly associated with respiratory distress(severe acute respiratory syndrome),metaanalysis have indicated that liver dysfunction also occurs in patients with severe symptoms.Current studies revealed distinctive patterning in the receptors on the hepatic cells that helps in viral invasion through the expression of angiotensinconverting enzyme receptors.It has also been reported that in some patients with COVID-19,therapeutic strategies,including repurposed drugs(mitifovir,lopinavir/ritonavir,tocilizumab,etc.)triggered liver injury and cholestatic toxicity.Several proven indicators support cytokine storm-induced hepatic damage.Because there are 1.5 billion patients with chronic liver disease worldwide,it becomes imperative to critically evaluate the molecular mechanisms concerning hepatotropism of COVID-19 and identify new potential therapeutics.This review also designated a comprehensive outlook of comorbidities and the impact of lifestyle and genetics in managing patients with COVID-19.

Toxicity and Molecular Mechanisms of Actions of Silver Nanoparticles

Silver nanoparticles (AgNPs) have gained popularity due to their antibacterial properties, and are therefore widely used in several applications such as wound dressings, food packaging, and water purification. However, the toxicity of AgNPs to humans and the environment is a growing concern. This review aims to summarize the current knowledge on the toxicity and molecular mechanisms of action of AgNPs. The toxicity of AgNPs can be attributed to their small size, which allows them to enter cells and interact with cellular components. Reports suggest that AgNPs can induce cell death, DNA damage, and oxidative stress in various cell types. The toxic effects of AgNPs differ based on their size, shape, surface charge, and coating. The molecular mechanisms behind the toxicity of AgNPs involve the production of reactive oxygen species, disruption of cellular membranes, and activation of proinflammatory cytokines. Overall, the toxicity of AgNPs is dependent on various factors, and more research is needed to fully understand the mechanisms behind their toxicity. This review highlights the need for proper risk assessments and regulations to minimize the adverse effects of AgNPs on human health and the environment.

Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma

Chronic infection with viral hepatitis affects half a billion individuals worldwide and can lead to cirrhosis,cancer,and liver failure.Liver cancer is the third leading cause of cancer-associated mortality,of which hepatocellular carcinoma(HCC)represents 90%of all primary liver cancers.Solid tumors like HCC are complex and have heterogeneous tumor genomic profiles contributing to complexity in diagnosis and management.Chronic infection with hepatitis B virus(HBV),hepatitis delta virus(HDV),and hepatitis C virus(HCV)are the greatest etiological risk factors for HCC.Due to the significant role of chronic viral infection in HCC development,it is important to investigate direct(viral associated)and indirect(immune-associated)mechanisms involved in the pathogenesis of HCC.Common mechanisms used by HBV,HCV,and HDV that drive hepatocarcinogenesis include persistent liver inflammation with an impaired antiviral immune response,immune and viral protein-mediated oxidative stress,and deregulation of cellular signaling pathways by viral proteins.DNA integration to promote genome instability is a feature of HBV infection,and metabolic reprogramming leading to steatosis is driven by HCV infection.The current review aims to provide a brief overview of HBV,HCV and HDV molecular biology,and highlight specific viral-associated oncogenic mechanisms and common molecular pathways deregulated in HCC,and current as well as emerging treatments for HCC.

Roles and molecular mechanisms of physical exercise in cancer prevention and treatment

Exercise can enhance motivation to change lifestyle behaviors,improve aerobic fitness,improve physical function,control fatigue,and enhance quality of life.Studies have demonstrated the benefits to be gained from physical exercise,highlighting the importance of popularizing the concept of physical exercise for individuals and making professional exercise-treatment programs available to patients with cancer.However,the correlation between physical exercise and carcinogenesis is easily overlooked,and exercise interventions are not routinely provided to patients with cancer,especially those with advanced cancer.In this article,we present a literature review of the effects of exercise on cancer development and progression and give recent evidence for the type of exercise best suited for different types of cancer and in different disease stages.Moreover,the molecular mechanisms about regulating metabolism and systemic immune function in cancer are summarized and discussed.In conclusion,physical exercise should be considered as an important intervention for preventing and treating cancer and its complications.

Molecular mechanisms of intermuscular bone development in fish:a review

Intermuscular bones(IBs)are slender linear bones embedded in muscle,which ossify from tendons through a process of intramembranous ossification,and only exist in basal teleosts.IBs are essential for fish swimming,but they present a choking risk during human consumption,especially in children,which can lead to commercial risks that have a negative impact on the aquaculture of these fish.In this review,we discuss the morphogenesis and functions of IBs,including their underlying molecular mechanisms,as well as the advantages and disadvantages of different methods for IB studies and techniques for breeding and generating IB-free fish lines.This review reveals that the many key genes involved in tendon development,osteoblast differentiation,and bone formation,e.g.,scxa,msxC,sost,twist,bmps,and osterix,also play roles in IB development.Thus,this paper provides useful information for the breeding of new fish strains without IBs via genome editing and artificial selection.

Molecular mechanisms of NMDA receptor-mediated excitotoxicity:implications for neuroprotective therapeutics for stroke

Excitotoxicity is a process observed in many disease states by which an excessive synaptic excitation causes neuronal death, and is thought to be triggered by the extracellular accumulation of the excitatory neurotransmitter glutamate, which binds and activates ionotropic N-methyl-D-aspartate glutamatergic receptors （NMDARs） in the brain. Normally, NMDARs mediate calcium entry into the cell to regulate physiological processes such as synaptic plasticity and memory,

Molecular mechanisms of cardiac aging

Age-associated changes in cardiovascular structure/ function are implicated in the markedly increased risk for cardiovascular disease in older persons. Aging not only prolongs exposure to several other cardiovascular risks, but also leads to intrinsic cardiac changes, which reduces cardiac functional reserve, predisposes the heart to stress and contributes to increased cardiovascular mortality in the elderly. Intrinsic cardiac aging in the murine model closely recapitulates age-related cardiac changes in humans, includ- ing left ventricular hypertrophy, fibrosis and diastolic dysfunction. Cardiac aging in mice is accompanied by accumulation of mitochondrial protein oxidation, increased mitochondrial DNA mutations, increased mitochondrial biogenesis, as well as decreased cardiac SERCA2 protein. All of these age-related changes are significantly attenu- ated in mice overexpressing catalase targeted to mitochondria （mCAT）. These findings demonstrate the critical role of rnitochondrial reactive oxygen species （ROS） in cardiac ag ing and support the potential antioxidants to cardiac aging lar diseases. application of mitochondrial and age-related cardiovascular diseases.

Clinical diagnosis and management of pancreatic cancer: Markers, molecular mechanisms, and treatment options

Pancreatic cancer(PC)is the third-leading cause of cancer deaths.The overall 5-year survival rate of PC is 9%,and this rate for metastatic PC is below 3%.However,the PC-induced death cases will increase about 2-fold by 2060.Many factors such as genetic and environmental factors and metabolic diseases can drive PC development and progression.The most common type of PC in the clinic is pancreatic ductal adenocarcinoma,comprising approximately 90%of PC cases.Multiple pathogenic processes including but not limited to inflammation,fibrosis,angiogenesis,epithelial-mesenchymal transition,and proliferation of cancer stem cells are involved in the initiation and progression of PC.Early diagnosis is essential for curable therapy,for which a combined panel of serum markers is very helpful.Although some mono or combined therapies have been approved by the United States Food and Drug Administration for PC treatment,current therapies have not shown promising outcomes.Fortunately,the development of novel immunotherapies,such as oncolytic viruses-mediated treatments and chimeric antigen receptor-T cells,combined with therapies such as neoadjuvant therapy plus surgery,and advanced delivery systems of immunotherapy will improve therapeutic outcomes and combat drug resistance in PC patients.Herein,the pathogenesis,molecular signaling pathways,diagnostic markers,prognosis,and potential treatments in completed,ongoing,and recruiting clinical trials for PC were reviewed.

Research progress on anticancer effects and molecular mechanisms of osthole

Cancer is a serious threat to human life and a big problem in clinical treatment.Some natural active substances extracted from Traditional Chinese Medicine can effectively inhibit the growth of cancer cells,which is a new direction for finding more effective anticancer drugs.Osthole is a natural coumarin compound extracted from Traditional Chinese Medicines such as Cnidium monnieri,Angelica pubescens and Peucedanum praeruptorum Dunn.It has significant inhibitory activity against a variety of cancers.This paper summarizes the anticancer effects and molecular mechanisms of osthole in the treatment of cancers in recent years in order to provide references for further research.

Research Progress on Molecular Mechanisms of Tumor Budding in Colorectal Cancer

Tumor buds are usually defined as isolated single cancer cells or clusters of up to four cancer cells located at the front of invasive tumors which play an important role in the clinical pathological study of colorectal cancer.The prognostic value of tumor budding in colorectal cancer has been supported by a large amount of evidence.However,its molecular mechanism remains unclear,and it is also a research hotspot now.This paper reviews the latest research progress on the molecular mechanisms of tumor budding in colorectal cancer.

Molecular mechanisms of apoptosis in hepatocellular carcinoma cells induced by ethanol extracts of Solanum lyratum Thumb through the mitochondrial pathway

AIM To explore the induction effects and mechanism of Solanum lyratum Thumb(ST) on human hepatocellularcarcinoma SMMC-7721 cells through the mitochondrial pathway.METHODS The experiments were conducted on three groups: an experimental group (with ST ethanol extracts' concentration being 2.5, 5 and 10 mg/L), a negative control group (with only nutrient solution, 0 mg/L ST ethanol extracts), and a positive control group (2.5 mg/L DDP). The inhibition rate of cell proliferation was checked by using the methyl thiazolyl tetrazolium method, and cell apoptosis was tested by TUNEL method. Furthermore, RT-PCR was used to examine m RNA expression of Fas, Fas L, caspase-8, caspase-3, p53 and Bcl-2 genes.RESULTS Compared with the negative control group, the inhibition and apoptosis rates of the experimental group with different concentrations of ST extracts on human hepatocellular carcinoma SMMC-7721 cells significantly increased(P<0.05). Besides, the m RNA expression of Fas L and Bcl-2 significantly decreased(P<0.05) while the m RNA expression of Fas, caspase-8, caspase-3 and p53 increased significantly. When compared with the positive control group, the experimental groups with 5 mg/L ST ethanol extracts showed effects similar to the positive control group.CONCLUSION ST ethanol extracts induced the apoptosis of hepatocellular carcinoma SMMC-7721 cells through up-regulated Fas, caspase-8, caspse-3 and p53, and down-regulated Fas L and Bcl-2 in the mitochondrial pathway.

Molecular mechanisms controlling seed set in cereal crop species under stress and non-stress conditions

Maximizing seed yield is the ultimate breeding goal in important cereal crop species. Seed set is a key developmental stage in the process of seed formation, which determines grain number, seed mass, and realized yield potential, and can be severely affected by abiotic and biotic stresses. However, seed set can also be substantially reduced by genetic factors even under optimal fertilization conditions. The underlying molecular genetic mechanisms are still obscure. In this review, we elucidate the process of seed set of cereal crop species in detail, including development of floral structures, formation of viable gametes, double fertilization, seed development, and abortion. We discuss how genetic and non-genetic factors affect seed set in different development stages. Finally, we will propose novel strategies to study genetic mechanisms controlling seed set and exploit genetic resources to improve seed set in cereal crop species.

The Neurovascular Unit Dysfunction in the Molecular Mechanisms of Epileptogenesis and Targeted Therapy

Epilepsy is a multifaceted neurological syndrome characterized by recurrent,spontaneous,and synchronous seizures.The pathogenesis of epilepsy,known as epileptogenesis,involves intricate changes in neurons,neuroglia,and endothelium,leading to structural and functional disorders within neurovascular units and culminating in the development of spontaneous epilepsy.Although current research on epilepsy treatments primarily centers around anti-seizure drugs,it is imperative to seek effective interventions capable of disrupting epileptogenesis.To this end,a comprehensive exploration of the changes and the molecular mechanisms underlying epileptogenesis holds the promise of identifying vital biomarkers for accurate diagnosis and potential therapeutic targets.Emphasizing early diagnosis and timely intervention is paramount,as it stands to significantly improve patient prognosis and alleviate the socioeconomic burden.In this review,we highlight the changes and molecular mechanisms of the neurovascular unit in epileptogenesis and provide a theoretical basis for identifying biomarkers and drug targets.

Molecular mechanisms of cisplatin resistance in ovarian cancer

Ovarian cancer is one of the most common malignant tumors of the female repro-ductive system.The majority of patients with advanced ovarian cancer are mainly treated with cisplatin-based chemotherapy.As the most widely used first-line anti-neoplastic drug,cisplatin produces therapeutic effects through multiple mechanisms.However,during clinical treat-ment,cisplatin resistance has gradually emerged,representing a challenge for patient outcome improvement.The mechanism of cisplatin resistance,while known to be complex and involve many processes,remains unclear.We hope to provide a new direction for pre-clin-ical and clinical studies through this review on the mechanism of ovarian cancer cisplatin resis-tance and methods to overcome drug resistance.