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 Mechanism and Molecular Design of Lubricating Oil Antioxidants

To overcome the limitations of traditional experimental“trial and error”methods in lubricant additive design,a new molecular design method based on molecular structure parameters is established here.The molecular mechanism of the antioxidant reaction of hindered phenol,diphenylamine,and alkyl sulfide are studied via molecular simulations.Calculation results show that the strong electron-donating ability and high hydrogen-donating activity of the antioxidant molecule and the low hydrogen-abstracting activity of free radicals formed after dehydrogenation are the internal molecular causes of the shielding of phenol and diphenylamine from scavenging peroxy free radicals,and the strong electron-donating ability is the internal molecular cause of the high activity of thioether in decomposing alkyl hydrogen peroxide.Based on this antioxidant molecular mechanism,a molecular design rule of antioxidant is proposed,namely“high EHOMO,large Q(S),low bond dissociation energy BDE(O—H)and BDE(N—H)”.Two new antioxidants,PAS-I and PAS-II,are designed and prepared by chemical bonding of hindered phenol,diphenylamine,and sulfur atoms.Experimental results show that these antioxidants both have excellent antioxidant effects in lubricating oil,and that PAS-II is the superior antioxidant,consistent with theoretical predictions.

Absorption characteristics,model,and molecular mechanism of hydrogen sulfide in morpholine acetate aqueous solution

The solubility of H_(2)S was measured in solutions of N-butyl-N-methylmorpholine acetate([Bmmorp][Ac])containing 20%-40%(mass)water at experimental temperatures ranged from 298.15 to 328.15 K and pressures up to 320 k Pa.The total solubility of H_(2)S increased with higher temperatures,lower pressures,and reduced water content.The reaction equilibrium thermodynamic model was used to correlate the solubility data.The results indicate that the chemical reaction equilibrium constant decrease with increasing water content and temperature,whereas Henry constant increase with increasing water content and temperature.Compared with other ionic liquids,H_(2)S exhibits a higher physical absorption enthalpy and a lower chemical absorption enthalpy in[Bmmorp][Ac]aqueous solution.This suggests that[Bmmorp][Ac]has a strong physical affinity for H_(2)S and low energy requirement for desorption.Quantum chemical methods were used to investigate the molecular mechanism of H_(2)S absorption in ionic liquids.The interaction energy analysis revealed that the binding of H_(2)S with the ionic liquid in a1:2 ratio is more stable.Detailed analyses by the methods of the interaction region indicator and the atoms in molecules were conducted to the interactions between H_(2)S and the ionic liquid.

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.

Transcriptome profiling and RXR gene family identification reveals the molecular mechanism of rapid aging after spawning of cuttlefish Sepiella japonica

Sepiella japonica is a worldwide marine cuttlefish species of high economic value.S.japonica routinely modifying behaviors in reproductive life,such as rapid aging until death after spawning,has been recognized in artificial breeding.However,reproductive behavior at the level of genes is rarely reported,thus,the research on the genetic basis of behavior,reproduction,and artificial breeding was limited.We applied RNA-seq in different stages of reproduction to investigate the reason of rapid aging after spawning,pre-maturity,pre-spawning after maturity,and post-spawning.The retinoid X receptor(RXR)gene family in S.japonica was identified,and 1343–1452 differentially expressed genes(DEGs)in all 3 stages of reproductive life were identified from pairwise m RNA comparisons.Furthermore,through the GO term and KEGG analysis,S.japonica could handle neuronal development and network formation before maturity and have a functional degradation of neural communication,signal transduction,vision,and gene expression after spawning.Eight Sj RXRαs have been identified and they played different roles in growth development or reproduction.Therefore,the regulation of several channels and receptors is the intrinsic molecular mechanism of rapid aging after spawning in S.japonica.This study revealed the survival strategy and provided fundamental data on the level of genes for understanding the reproductive behavior and the reproduction of S.japonica.

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.

Boswellic acids: a review on its pharmacological properties, molecular mechanism and bioavailability

Boswellic acids is a general term for a series of pentacyclic triterpenoid compounds that are isolated from the oleogin resin of the Boswellia genus and serve as the main active ingredient.It exhibits a wide range of biological activities,such as anti-inflammatory,anti-cancer,antibacterial,antiviral,hepatoprotective,neuroprotective,anti-diabetic,and anti-thrombotic properties.As a result,it has gained significant recognition among practitioners of traditional Chinese and Indian medicine.These biological effects may be associated with multiple molecular targets and signal transduction pathways.However,the poor pharmacokinetic properties of the substance lead to lower bioavailability,which affects its effectiveness.To address this issue,scientists have proposed a number of strategies,such as solid dispersions,phytosome®technologies,and novel drug delivery systems.This article aims to provide a comprehensive overview for boswellic acids on the phytochemistry,molecular mechanisms,potential therapeutic applications,and strategies to improve bioavailability.

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.

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.

Advances in Molecular Regulatory Mechanisms of Fruit Trees under Low Temperature Stress

The most recent research findings on the tolerance of fruit trees to cold stress are reviewed from a molecular perspective,including the perception and transduction of low temperature calcium signaling,CBF-dependent molecular regulatory mechanisms,non-CBF-dependent molecular regulatory mechanisms,and so forth.The objective is to provide a reference basis for further improving the cold resistance of fruit trees and cultivating new varieties of hardy plants.

Molecular Mechanism of KDM5B Development in Hepatocellular Carcinoma

Objective: To investigate the mechanism of cell cyclin-dependent kinase (KDM5B), a key enzyme driving all cell cycle transitions, promoting HCC progression and metastasis. Methods: The expression of KDM5B in normal liver, HCC and its adjacent tissues was analyzed by RT-PCR and IHC. Lentivirus transfection method was used to construct stable cell lines with KDM5B overexpression and down-regulation, and the role of KDM5B in HCC migration and invasion was detected at cell level and animal level. Western blotting and Transwell experiments were performed to verify the effect of KDM5B and/or CCR2 inhibitors on HCC progression and metastasis by using liver orthotopic transplantation tumor model and immunofluorescence methods. Results: RT-PCR showed that the expression level of KDM5B in HCC was significantly higher than that in adjacent tissues, and the increase of KDM5B was relatively significant. Upregulation of KDM5B in nude mouse liver orthotopic transplantation tumor model can promote the incidence of lung metastasis and shorten the survival time of nude mice, whereas upregulation of KDM5B can reduce the incidence of lung metastasis and prolong the survival time of nude mice. Conclusion: This study clarified the expression of KDM5B in HCC and its function in promoting HCC migration, invasion and metastasis. The molecular mechanism of KDM5B promoting HCC metastasis was revealed, providing a potential therapeutic target for HCC.

Studies on Molecular Mechanism of Human Early Cardiogenesis Using the Drosophila as a Model System

Recently,some of the genetic mechanisms of heart specification have been elucidated in Drosophila .However,genes involved in early cardiogenesis of human remain to be identified.Since the pathways that regulate early cardiac fate determination are conserved between Drosophila and vertebrates,flies can be used as a model test system to explore the genetic basis of cardiogenesis in human.In this project,about 3000 reccieve lethal gene lines were produced by P or EMS mutagenesis.With staining of antibodies against heart precussor cells of Drosophila ,about 200 lines were observed to show heart phenotype.In pilot studies of their function with RNAi technique,the RNAi phenotypes of several genes tested were observed,which were very similar to that of their mutants,showing heart tube defects or no heart precursors formation.Taking advantage of the advanced genetic information available in the Drosophila and human systems,we have identified about 50 human transcripts homologous to the Drosophila heart related gene candidates.Northern blot analysis for some of the human candidates showed that several genes were expressed in both adult and early embryonic tissues,which may help in the evaluation of candidate genes for human cardiogenesis.Our further experiments with transgenic flies generated with wild type and mutant forms of these candidate genes to examine for defects in cardiogenesis or cardiac function are under way.The candidate genes producing cardiac specific defects suggestive of similarities to the heart disease syndromes can then be pursued further as likely disease gene candidates.Such an approach is likely to provide a dramatic reduction of possible candidate genes,or to screen and identify mutations that may generate the disease in human.

Advances in Studies on Molecular Mechanism of Salt Tolerance in Dunaliella salina

Dunaliella salina is known as one of the most salt-tolerant eukaryotic or- ganisms, and the most ideal model organism for studying plant adaption to high salinity. In recent years, the study on molecular mechanism of salt tolerance in Dunaliella salina has become the focus of scholars at home and abroad with the development of molecular biological techniques. This study reviewed studies on adaption of Dunaliella salina to high salinity in aspects of osmotic adjustment, salt tolerance-related genes and proteins of Dunaliella salina and signal transduction pathway of salt stress.

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.

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.

Saline-Alkali Tolerance in Rice: Physiological Response, Molecular Mechanism, and QTL Identification and Application to Breeding

Salinity-alkalinity is incipient abiotic stress that impairs plant growth and development.Rice(Oryza sativa)is a major food crop greatly affected by soil salinity and alkalinity,requiring tolerant varieties in the saline-alkali prone areas.Understanding the molecular and physiological mechanisms of saline-alkali tolerance paves the base for improving saline-alkali tolerance in rice and leads to progress in breeding.This review illustrated the physiological consequences,and molecular mechanisms especially signaling and function of regulating genes for saline-alkali tolerance in rice plants.We also discussed QTLs regarding saline-alkali tolerance accordingly and ways of deployment for improvement.More efforts are needed to identify and utilize the identified QTLs for saline-alkali tolerance in rice.

Clinical Efficacy and Molecular Mechanism of Nourishing Shen and Supplementing Marrow Principle in Treating β Thalassemia

Objective: To explore the possibility of using traditional Chinese medicine (TCM) in treating β thalassemia, its clinical effect and molecular mechanism of the action.Methods: According to the TCM theory of“Shen producing marrow”, the composite recipe, Yisui Shenxueling Granule (YSSXL), consisting of Chinese drugs for nourishing Shen and supplementing marrow (NS&SM) was given orally to 7 8 patients with β thalassemia (49 of the severe type and 29 of moderate type ), 3 times a day, 10 g each time (for children, the dose would be reduced proper ly), with 3 months as one therapeutic course, and no blood transfusion used in t he course. The clinical therapeutic efficacy and hematologic parameters in patie nts were observed, and systemic gene analysis was conducted with PAGE, PCR, PCR SSCP, RT PCR and DNA sequences analysis and mRNA detection, in order to s tudy the molecular mechanism from the relationships between genetic mutation and clinical efficacy, gene expression and its regulation. Results: YSSXL showed obvious therapeutic effect in treating β thalassemia. Gene analysis revealed that it did not change the genetic mutatio n type, but could obviously increase hemoglobin, fetal hemoglobin (HbF), γ/(β+ γ) globin ratio, γ globin mRNA expression and GM CSF mRNA expression in patients, as well as the GM CSFmRMA in marrow of mice after 60 Co radia tion. Conclusion: YSSXL has a remarkable therapeutic effect on β tha lassemia, and its possible mechanism is its action in unlocking γ gene, in creasing the γ globin expression and enhancing HbF synthesis so as to compe nsate for the gene defect. This study has opened a new path for the treatment of β thalassemia with TCM.

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.

The potential molecular mechanism of overexpression of uPA, IL-8, MMP-7 and MMP-9 induced by TRAIL in pancreatic cancer cell

BACKGROUND: TNF-related apoptosis-inducing ligand (TRAIL) is a death ligand of the TNF-superfamily that has been implicated in inducing apoptosis in some tumor cells. The purpose of this study was to find out if TRAIL could induce the expression of uPA, IL-8, MMP-7 and MMP-9. and to explore the corresponding potential signaling transduction pathway in pancreatic cancer cells. METHODS: Colo357wt, Panc89 and PancTu I cell lines were stimulated by TRAIL (100 ng/ml). Crystal violet cell vitality assay was used to check the sensitivity to TRAIL-induced apoptosis. Real-time RT-PCR tested the expression of uPA, IL-8, MMP-7 and MMP-9. RESULTS: TRAIL can stimulate the expression of uPA, IL-8, MMP-7 and MMP-9 in pancreatic cancer cell lines, especially in Colo357wt. The members of caspases, MEK1/2, PKC, and NF-kappa B are involved in TRAIL-induced expression of uPA, IL-8, MMP-7 and MMP-9. Furthermore, caspases play a different role in Colo357wt, Panc89 and PancTu I. CONCLUSIONS: TRAIL-treatment may result in the enhancement of invasion involving the signaling pathways of caspases, MEK1/2, PKC and NF-kappa B, in pancreatic cancer cells. It points to the necessity to carefully evaluate in vivo side effects of TRAIL.