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.

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 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 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.

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 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.

Tocotrienol isoforms:The molecular mechanisms underlying their effects in cancer therapy and their implementation in clinical trials

Tocotrienols are found in a variety of natural sources,like rice bran,annatto seeds and palm oil,and have been shown to have several health-promoting properties,particularly against chronic diseases such as cancer.The incidence of cancer is rapidly increasing around the world,not only a result of continued aging and population growth,but also due to the adoption of aspects of the Western lifestyle,such as high-fat diets and low-physical activity.The literature provides strong evidence that tocotrienols are able to inhibit the growth of various cancers,including breast,lung,ovarian,prostate,liver,brain,colon,myeloma and pancreatic cancers.These findings,along with the reported safety profile of tocotrienols in healthy human volunteers,encourage further research into these compounds’potential use in cancer prevention and treatment.The current review provided detailed information about the molecular mechanisms of action of different tocotrienol isoforms in various cancer models and evaluated the potential therapeutic effects of different vitamin E analogues on important cancer hallmarks,such as cellular proliferation,apoptosis,angiogenesis and metastasis.MEDLINE/PubMed and Scopus databases were used to identify recently published articles that investigated the anticancer effects of vitamin E derivatives in various types of cancer in vitro and in vivo along with clinical evidence of adjuvant chemopreventive benefits.Following an overview of pre-clinical studies,we describe several completed and ongoing clinical trials that are paving the way for the successful implementation of tocotrienols in cancer chemotherapy.

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 mechanisms of adaptive evolution in wild animals and plants

Wild animals and plants have developed a variety of adaptive traits driven by adaptive evolution,an important strategy for species survival and persistence.Uncovering the molecular mechanisms of adaptive evolution is the key to understanding species diversification,phenotypic convergence,and inter-species interaction.As the genome sequences of more and more non-model organisms are becoming available,the focus of studies on molecular mechanisms of adaptive evolution has shifted from the candidate gene method to genetic mapping based on genome-wide scanning.In this study,we reviewed the latest research advances in wild animals and plants,focusing on adaptive traits,convergent evolution,and coevolution.Firstly,we focused on the adaptive evolution of morphological,behavioral,and physiological traits.Secondly,we reviewed the phenotypic convergences of life history traits and responding to environmental pressures,and the underlying molecular convergence mechanisms.Thirdly,we summarized the advances of coevolution,including the four main types:mutualism,parasitism,predation and competition.Overall,these latest advances greatly increase our understanding of the underlying molecular mechanisms for diverse adaptive traits and species interaction,demonstrating that the development of evolutionary biology has been greatly accelerated by multi-omics technologies.Finally,we highlighted the emerging trends and future prospects around the above three aspects of adaptive evolution.

Roles and Molecular Mechanisms of Biomarkers in Hepatocellular Carcinoma with Microvascular Invasion: A Review

Hepatocellular carcinoma(HCC)being a leading cause of cancer-related death,has high associated mortality and recurrence rates.It has been of great necessity and urgency to find effective HCC diagnosis and treatment measures.Studies have shown that microvascular invasion(MVI)is an independent risk factor for poor prognosis after hepatectomy.The abnormal expression of biomacromolecules such as circ-RNAs,lncRNAs,STIP1,and PD-L1 in HCC patients is strongly correlated with MVI.Deregulation of several markers mentioned in this review affects the proliferation,invasion,metastasis,EMT,and anti-apoptotic processes of HCC cells through multiple complex mechanisms.Therefore,these biomarkers may have an important clinical role and serve as promising interventional targets for HCC.In this review,we provide a comprehensive overview on the functions and regulatory mechanisms of MVI-related biomarkers in HCC.

Biomolecular mechanisms of epileptic seizures and epilepsy: a review

Epilepsy is a recurring neurological disease caused by the abnormal electrical activity in the brain. This disease has caused about 50 new cases in 100,000 populations every year with the clinical manifestations of awareness loss, bruising, and mobility abnormalities. Due to the lack understanding of the pathophysiology behind the illness, a wide variety of medications are available to treat epilepsy. Epileptogenesis is the process by which a normally functioning brain undergoes alterations leading to the development of epilepsy, involving various factors. This is related to the inflammation which is driven by cytokines like IL-1 and tumor necrosis factor-α (TNF-α) leads to neuronal hyperexcitability. Pro-inflammatory cytokines from activated microglia and astrocytes in epileptic tissue initiate an inflammatory cascade, heightening neuronal excitability and triggering epileptiform activity. The blood-brain barrier (BBB) maintains central nervous system integrity through its tight endothelial connections, but inflammation impact BBB structure and function which leads to immune cell infiltration. The mammalian target of rapamycin (mTOR) pathway’s excessive activation influences epileptogenesis, impacting neuronal excitability, and synapse formation, with genetic mutations contributing to epilepsy syndromes and the modulation of autophagy playing a role in seizure onset. The apoptotic pathway contribute to cell death through glutamate receptor-mediated excitotoxicity, involving pro-apoptotic proteins like p53 and mitochondrial dysfunction, leading to the activation of caspases and the disruption of calcium homeostasis. Ionic imbalances within neural networks contribute to the complexity of epileptic seizures, involving alterations in voltage-gated sodium and potassium channels, and the formation of diverse ion channel subtypes. Epileptogenesis triggers molecular changes in hippocampus, including altered neurogenesis and enhanced expression of neurotrophic factors and proteins. Oxidative stress leads to cellular damage, disrupted antioxidant systems, and mitochondrial dysfunction, making it a key player in epileptogenesis and potential neuroprotective interventions. Thalamocortical circuitry disruption is central to absence epilepsy, the normal circuit becomes faulty and results in characteristic brain wave patterns.

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.

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.

Molecular mechanisms governing plant responses to high temperatures

The increased prevalence of high temperatures （HTs） around the world is a major global concern, as they dramatically affect agronomic productivity. Upon HT exposure, plants sense the temperature change and initiate cellular and metabolic responses that enable them to adapt to their new environmental conditions.Decoding the mechanisms by which plants cope with HT will facilitate the development of molecular markers to enable the production of plants with improved thermotolerance. In recent decades, genetic, physiological, molecular, and biochemical studies have revealed a number of vital cellular components and processes involved in thermoresponsive growth and the acquisition of thermo- tolerance in plants. This review summarizes the major mechanisms involved in plant HT responses, with a special focus on recent discoveries related to plant thermosensing, heat stress signaling, and HT-regulated gene expression networks that promote plant adaptation to elevated environmental temperatures.