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...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.展开更多
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 li...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.展开更多
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 postu...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.展开更多
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)...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.展开更多
High incidence(10.2%)and mortality(9.2%)rates led to the ranking of colorectal cancer(CRC)as the second most malignant tumor spectrum worldwide in 2020.Treatment strategies are becoming highly dependent on the molecul...High incidence(10.2%)and mortality(9.2%)rates led to the ranking of colorectal cancer(CRC)as the second most malignant tumor spectrum worldwide in 2020.Treatment strategies are becoming highly dependent on the molecular characteristics of CRC.The classical theories accept two models depicting the origin of CRC:The progression of adenoma to cancer and transformation from serrated polyps to cancer.However,the molecular mechanism of CRC development is very complex.For instance,CRCs originating from laterally spreading tumors(LST)do not adhere to any of these models and exhibit extremely serious progression and poor outcomes.In this article,we present another possible pathway involved in CRC development,particularly from LST,with important molecular characteristics,which would facilitate the design of a novel strategy for targeted therapy.展开更多
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...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.展开更多
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 he...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.展开更多
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 sal...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.展开更多
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 phys...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.展开更多
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 connections between neurons undergo activi...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 connections between neurons undergo activity-dependent functional 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。展开更多
Since the outbreak of the novel corona virus disease 2019(COVID-19)at the end of 2019,specific antiviral drugs have been lacking.A Chinese patent medicine Toujiequwen granules has been promoted in the treatment of COV...Since the outbreak of the novel corona virus disease 2019(COVID-19)at the end of 2019,specific antiviral drugs have been lacking.A Chinese patent medicine Toujiequwen granules has been promoted in the treatment of COVID-19.The present study was designed to reveal the molecular mechanism of Toujiequwen granules against COVID-19.A network pharmacological method was applied to screen the main active ingredients of Toujiequwen granules.Network analysis of 149 active ingredients and 330 drug targets showed the most active ingredient interacting with many drug targets is quercetin.Drug targets most ffected by the active ingredients were PTGS2,PTGS1,and DPP4.Drug target disease enrichment analysis showed drug targets were significantly enriched in cardiovascular diseases and digestive tract diseases.An"active ingredient-target-disease"network showed that 57 active ingredients from Toujiequwen granules interacted with 15 key targets of COVID-19.There were 53 ingredients that could act on DPP4,suggesting that DPP4 may become a potential new key target for the treatment of COVID-19.GO analysis results showed that key targets were mainly enriched in the cellular response to lipopolysaccharide,cytokine activity and other functions.KEGG analysis showed they were mainly concentrated in viral protein interaction with cytokine and cytokine receptors and endocrine resistance pathway.The evidence suggests that Toujiequwen granules might play an effective role by improving the symptoms of underlying diseases in patients with COVID-19 and multi-target interventions against mutiple signaling pathways related to the pathogenesis of COVID-19.展开更多
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 ...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.展开更多
Aim:The oxidized low-density lipoprotein(OxLDL) plays an important role in atherosclerosis yet it remains unclear if it damages circulating erythrocytes. Method: In this study。
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 b...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.展开更多
The mutagenic effects of discharge plasma and plasma+PAW(plasma and its activated water combined) on Astragalus adsurgens Pall seeds were explored. Needle array-plate dielectric-barrier discharge plasma was used to tr...The mutagenic effects of discharge plasma and plasma+PAW(plasma and its activated water combined) on Astragalus adsurgens Pall seeds were explored. Needle array-plate dielectric-barrier discharge plasma was used to treat A. adsurgens Pall seeds and PAW was prepared at the same time.The deionized water and the obtained PAW were used to cultivate plasma-treated seeds in groups and the survival rate of each group was counted. Results showed that the survival rate of the treated seeds of A. adsurgens Pall when cultured with deionized water was not significantly different from that of the control check(CK). The culture with PAW had an obvious lethal effect and each group reached the half-lethal dose. Reactive oxygen species(ROS) and RNA-Seq analysis of seedlings in the 3 h treatment group showed that the content of ROS in the 3 d post-treatment group was significantly higher than that of the CK. Because expression of the gene with the function of scavenging superoxide free radicals was upregulated, the ROS content of seedlings on the sixth day was significantly lower than that on the third day. Plasma and plasma+PAW treatments changed a large number of gene expressions;particularly, the plasma+PAW group caused plant-growth genes to be significantly upregulated. After treatment, the seedlings of A. adsurgens Pall may grow faster and have higher nutritional value. This research is of great significance to the wider application of isoelectronic bodies and their activated water physicochemical mutagens in biological effects and breeding research.展开更多
Myocardial ischemia/reperfusion(I/R)injury is a pathological change that occurs during the restoration of blood supply to ischemic or occluded coronary arteries after coronary heart disease,stroke,cardiac arrest and r...Myocardial ischemia/reperfusion(I/R)injury is a pathological change that occurs during the restoration of blood supply to ischemic or occluded coronary arteries after coronary heart disease,stroke,cardiac arrest and resuscitation,organ transplantation,shock and other events.Myocardial I/R injury is often accompanied by cardiovascular adverse events,which seriously affect the prognosis of myocardial ischemia.The potential mechanism of myocardial I/R injury is complex,involving many pathological processes,such as oxygen free radical injury,calcium overload,inflammation,apoptosis,activation,immune imbalance,endoplasmic reticulum stress,autophagy,myocardial energy metabolism disorder,myocardial microvascular endothelial cell injury and so on.Ischemic preconditioning is an effective preventive and therapeutic measure to reduce ischemia-reperfusion(I/R)injury.At present,there are many experimental studies on the pathogenesis and prevention and treatment measures,but the clinical application is still limited,so the prevention and treatment of I/R injury is still a major challenge.The pathogenesis of myocardial I/R injury is not completely clear,and the treatment methods and drugs are limited,so this paper summarizes the molecular mechanism and related signal pathways involved in its injury,as well as the emerging targeted therapy,to provide strategy and theoretical basis for clinical prevention and treatment of myocardial I/R injury.展开更多
Objective:To investigate the potential molecular mechanism of Guijianyu(Euonymus Alatus)in the treatment of type 2 diabetes by network pharmacology approach.Methods:Relevant literature and Traditional Chinese Medicine...Objective:To investigate the potential molecular mechanism of Guijianyu(Euonymus Alatus)in the treatment of type 2 diabetes by network pharmacology approach.Methods:Relevant literature and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)were searched to screen the main active ingredients and targets of Guijianyu.The GeneCards database and OMIM database were searched to obtain target datasets for type 2 diabetes.And sorted out the intersection targets of drug and disease.The"drug-ingredient-target-disease"network model was constructed with the help of Cytoscape software,the protein-protein interaction(PPI)network was drawn using the STRING platform,and gene function and metabolic pathway enrichment analysis were also performed on the relevant targets of Guijianyu in the treatment of type 2 diabetes.Results:After the screening,8 main active ingredients and 154 drug-disease common targets were obtained,of which JUN,MAPK1,AKT1,RELA,and IL6 may be the key regulatory genes of Guijianyu in the treatment of type 2 diabetes.GO enrichment analysis yielded a total of 153 biological processes,mainly including nuclear receptor activity,transcription factor activity,direct ligand regulated sequence-specific DNA binding,steroid hormone receptor activity,cytokine receptor binding.KEGG analysis was enriched to a total of 156 significant pathways,mainly including AGE-RAGE signaling pathway in diabetic complications,fluid shear stress and atherosclerosis,hepatitis B,prostate cancer,kaposi sarcoma-associated herpesvirus infection.Conclusion:Studies based on network pharmacology show that various active ingredients such as quercetin and kaempferol in Guijianyu could act on multiple targets such as JUN,MAPK1,AKT1,RELA,and IL6.It may play a role in the treatment of type 2 diabetes and related complications by synergistically regulating glucose and lipid metabolism,reducing insulin resistance,protecting pancreatic beta-cell function,anti-oxidative stress,anti-inflammatory repair and so on.展开更多
Yield loss caused by crop diseases seriously restricts global food security.Breeding disease-resistant varieties with resistance(R)genes is acknowledged as the most economical and effective way to control diseases.The...Yield loss caused by crop diseases seriously restricts global food security.Breeding disease-resistant varieties with resistance(R)genes is acknowledged as the most economical and effective way to control diseases.Therefore,exploring broad-spectrum resistance(BSR)genes to pathogens and clarifying the underlying mechanism are the basis for effective utilization of BSR resources and finding new approaches for disease control.In the past 20 years,significant progress has also been made in plant immune mechanism and remarkable achievements have been made in researches on broad-spectrum disease resistance of major grain crops,and the potential molecular mechanisms of some BSR have been revealed.Here,the advances of broad-spectrum disease resistance in rice(including the representative cloned BSR genes and their molecular mechanisms)were reviewed.In addition,the problems,opportunities and challenges encountered by BSR were analyzed,and the development of BSR research and its application in rice production were prospected.展开更多
Objective: To study the molecular mechanism of Xinyi San for the treatment of senile rhinitis by applying network pharmacological analysis technology. Methods: The effective components and corresponding targets of Xin...Objective: To study the molecular mechanism of Xinyi San for the treatment of senile rhinitis by applying network pharmacological analysis technology. Methods: The effective components and corresponding targets of Xinyi San were collected by TCMSP. The targets of senile rhinitis were collected by the Genecards database. The potential target of Xinyi San in the treatment of senile rhinitis was obtained by Venn analysis. Cytoscape 3.7.2 the software constructs the relationship network model of “disease-single drug-active ingredient-action target”. Protein protein interaction (PPI) network was constructed by using a string database. R4.1.1 software was used for GO function enrichment analysis and KEGG pathway enrichment analysis. Results: In this study, we obtained 158 active ingredients, 40 potential therapeutic targets, 74 GO projects, and 99 pathways. Major pathways include Lipid and atherosclerosis, Chemical carcinogenesis-receptor activation, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway in diabetic complications, Pathways of neurodegeneration-multiple diseases, etc. Conclusion: Xinyi San has the characteristics of multi-component, multi-target, and multi-channel in the treatment of senile rhinitis. This study provides a basis for the in-depth study of Xinyi San.展开更多
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...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.展开更多
基金Financial support from the National Natural Science Foundation of China(21775081)Shandong Province Natural Science Foundation(ZR2020MB145)。
文摘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.
文摘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.
文摘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.
基金Supported by the Science and Engineering Research Board India grant,No.TAR/2020/000430 and EEQ/2020/000188Indian Council of Medical Research grant,No.BMI/12(08)/2021-6329.
文摘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.
基金Supported by the National Natural Science Foundation of China,No.72171170 and 82071964.
文摘High incidence(10.2%)and mortality(9.2%)rates led to the ranking of colorectal cancer(CRC)as the second most malignant tumor spectrum worldwide in 2020.Treatment strategies are becoming highly dependent on the molecular characteristics of CRC.The classical theories accept two models depicting the origin of CRC:The progression of adenoma to cancer and transformation from serrated polyps to cancer.However,the molecular mechanism of CRC development is very complex.For instance,CRCs originating from laterally spreading tumors(LST)do not adhere to any of these models and exhibit extremely serious progression and poor outcomes.In this article,we present another possible pathway involved in CRC development,particularly from LST,with important molecular characteristics,which would facilitate the design of a novel strategy for targeted therapy.
文摘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.
基金Supported by Canada Research Chair ProgramAlberta Innovates Strategic Research Projects,No.G2018000880and Calgary Clinical Research Fund Pilot,No.CRF18-0704.
文摘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.
基金funded by the Key-Area Research and Development Program of Guangdong Province,China(Grant No.2020B020219004)the Hainan Yazhou Bay Seed Lab(Grant No.B21HJ0216)the Agricultural Science and Technology Innovation Program and the Cooperation and Innovation Mission,China(Grant No.CAAS-ZDXT202001)。
文摘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.
文摘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.
基金supported by grant SDU2020 to Prof.Bente Finsen and Prof.Martin R.Larsen(COPING AD–Collaborative Project on the Interaction between Neurons and Glia in Alzheimer’s Disease)
文摘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 connections between neurons undergo activity-dependent functional 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。
基金was supported by the grants from the Education Department of Liaoning Province(No.LFW201701)Liaoning Provincial Key R&D Project(No.2020JH2/10300114)Key Laboratory of Shenyang Science and Technology Bureau(No.18-007-0-02)。
文摘Since the outbreak of the novel corona virus disease 2019(COVID-19)at the end of 2019,specific antiviral drugs have been lacking.A Chinese patent medicine Toujiequwen granules has been promoted in the treatment of COVID-19.The present study was designed to reveal the molecular mechanism of Toujiequwen granules against COVID-19.A network pharmacological method was applied to screen the main active ingredients of Toujiequwen granules.Network analysis of 149 active ingredients and 330 drug targets showed the most active ingredient interacting with many drug targets is quercetin.Drug targets most ffected by the active ingredients were PTGS2,PTGS1,and DPP4.Drug target disease enrichment analysis showed drug targets were significantly enriched in cardiovascular diseases and digestive tract diseases.An"active ingredient-target-disease"network showed that 57 active ingredients from Toujiequwen granules interacted with 15 key targets of COVID-19.There were 53 ingredients that could act on DPP4,suggesting that DPP4 may become a potential new key target for the treatment of COVID-19.GO analysis results showed that key targets were mainly enriched in the cellular response to lipopolysaccharide,cytokine activity and other functions.KEGG analysis showed they were mainly concentrated in viral protein interaction with cytokine and cytokine receptors and endocrine resistance pathway.The evidence suggests that Toujiequwen granules might play an effective role by improving the symptoms of underlying diseases in patients with COVID-19 and multi-target interventions against mutiple signaling pathways related to the pathogenesis of COVID-19.
基金This work was supported by the National Natural Science Foundation of China(U1702233 and U1902202)Program of the Chinese Academy of Sciences(XDA24030505 and XDA23080502)Program of Yunnan Provincial Science and Technology Department(202003AD150017 and 2018FY001-007)。
文摘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.
基金supported by National Natural Science Foundation of China(NSFC10572159)supported by "111 Project" entitled "Biomechanics&Tissue Repair Engineering"(No.:B06023)Chongqing Science&Technology Council(CSTC 2006ba5010)
文摘Aim:The oxidized low-density lipoprotein(OxLDL) plays an important role in atherosclerosis yet it remains unclear if it damages circulating erythrocytes. Method: In this study。
文摘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.
基金supported by National Natural Science Foundation of China (Nos. 51767020 and 52067017)the Inner Mongolia Autonomous Region Science and Technology Plan Project (No. 2020GG0280)the Natural Science Foundation of Inner Mongolia Autonomous Region (Nos. 2019MS06025 and 2020MS01016)。
文摘The mutagenic effects of discharge plasma and plasma+PAW(plasma and its activated water combined) on Astragalus adsurgens Pall seeds were explored. Needle array-plate dielectric-barrier discharge plasma was used to treat A. adsurgens Pall seeds and PAW was prepared at the same time.The deionized water and the obtained PAW were used to cultivate plasma-treated seeds in groups and the survival rate of each group was counted. Results showed that the survival rate of the treated seeds of A. adsurgens Pall when cultured with deionized water was not significantly different from that of the control check(CK). The culture with PAW had an obvious lethal effect and each group reached the half-lethal dose. Reactive oxygen species(ROS) and RNA-Seq analysis of seedlings in the 3 h treatment group showed that the content of ROS in the 3 d post-treatment group was significantly higher than that of the CK. Because expression of the gene with the function of scavenging superoxide free radicals was upregulated, the ROS content of seedlings on the sixth day was significantly lower than that on the third day. Plasma and plasma+PAW treatments changed a large number of gene expressions;particularly, the plasma+PAW group caused plant-growth genes to be significantly upregulated. After treatment, the seedlings of A. adsurgens Pall may grow faster and have higher nutritional value. This research is of great significance to the wider application of isoelectronic bodies and their activated water physicochemical mutagens in biological effects and breeding research.
基金National Natural Science Foundation of China(No.81660064)。
文摘Myocardial ischemia/reperfusion(I/R)injury is a pathological change that occurs during the restoration of blood supply to ischemic or occluded coronary arteries after coronary heart disease,stroke,cardiac arrest and resuscitation,organ transplantation,shock and other events.Myocardial I/R injury is often accompanied by cardiovascular adverse events,which seriously affect the prognosis of myocardial ischemia.The potential mechanism of myocardial I/R injury is complex,involving many pathological processes,such as oxygen free radical injury,calcium overload,inflammation,apoptosis,activation,immune imbalance,endoplasmic reticulum stress,autophagy,myocardial energy metabolism disorder,myocardial microvascular endothelial cell injury and so on.Ischemic preconditioning is an effective preventive and therapeutic measure to reduce ischemia-reperfusion(I/R)injury.At present,there are many experimental studies on the pathogenesis and prevention and treatment measures,but the clinical application is still limited,so the prevention and treatment of I/R injury is still a major challenge.The pathogenesis of myocardial I/R injury is not completely clear,and the treatment methods and drugs are limited,so this paper summarizes the molecular mechanism and related signal pathways involved in its injury,as well as the emerging targeted therapy,to provide strategy and theoretical basis for clinical prevention and treatment of myocardial I/R injury.
基金Chinese Medicine Inheritance and Innovation"Millions"Talent Project(Zhang Farong National Famous Traditional Chinese Medicine Inheritance Studio Construction Project)(No.2100409-Major Public Health Project CJJ2018014)。
文摘Objective:To investigate the potential molecular mechanism of Guijianyu(Euonymus Alatus)in the treatment of type 2 diabetes by network pharmacology approach.Methods:Relevant literature and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)were searched to screen the main active ingredients and targets of Guijianyu.The GeneCards database and OMIM database were searched to obtain target datasets for type 2 diabetes.And sorted out the intersection targets of drug and disease.The"drug-ingredient-target-disease"network model was constructed with the help of Cytoscape software,the protein-protein interaction(PPI)network was drawn using the STRING platform,and gene function and metabolic pathway enrichment analysis were also performed on the relevant targets of Guijianyu in the treatment of type 2 diabetes.Results:After the screening,8 main active ingredients and 154 drug-disease common targets were obtained,of which JUN,MAPK1,AKT1,RELA,and IL6 may be the key regulatory genes of Guijianyu in the treatment of type 2 diabetes.GO enrichment analysis yielded a total of 153 biological processes,mainly including nuclear receptor activity,transcription factor activity,direct ligand regulated sequence-specific DNA binding,steroid hormone receptor activity,cytokine receptor binding.KEGG analysis was enriched to a total of 156 significant pathways,mainly including AGE-RAGE signaling pathway in diabetic complications,fluid shear stress and atherosclerosis,hepatitis B,prostate cancer,kaposi sarcoma-associated herpesvirus infection.Conclusion:Studies based on network pharmacology show that various active ingredients such as quercetin and kaempferol in Guijianyu could act on multiple targets such as JUN,MAPK1,AKT1,RELA,and IL6.It may play a role in the treatment of type 2 diabetes and related complications by synergistically regulating glucose and lipid metabolism,reducing insulin resistance,protecting pancreatic beta-cell function,anti-oxidative stress,anti-inflammatory repair and so on.
基金Supported by Guangzhou Science and Technology Planning Project(202002030001)Fund for Modern Agro-Industry Technology Research System(CARS-01-32,2020KJ105)+1 种基金"Fourteenth Five-Year"New Discipline Team Building Project of Guangdong Academy of Agricultural Sciences(202116TD)Natural Science Foundation of Guangdong(2020A1515011213)。
文摘Yield loss caused by crop diseases seriously restricts global food security.Breeding disease-resistant varieties with resistance(R)genes is acknowledged as the most economical and effective way to control diseases.Therefore,exploring broad-spectrum resistance(BSR)genes to pathogens and clarifying the underlying mechanism are the basis for effective utilization of BSR resources and finding new approaches for disease control.In the past 20 years,significant progress has also been made in plant immune mechanism and remarkable achievements have been made in researches on broad-spectrum disease resistance of major grain crops,and the potential molecular mechanisms of some BSR have been revealed.Here,the advances of broad-spectrum disease resistance in rice(including the representative cloned BSR genes and their molecular mechanisms)were reviewed.In addition,the problems,opportunities and challenges encountered by BSR were analyzed,and the development of BSR research and its application in rice production were prospected.
文摘Objective: To study the molecular mechanism of Xinyi San for the treatment of senile rhinitis by applying network pharmacological analysis technology. Methods: The effective components and corresponding targets of Xinyi San were collected by TCMSP. The targets of senile rhinitis were collected by the Genecards database. The potential target of Xinyi San in the treatment of senile rhinitis was obtained by Venn analysis. Cytoscape 3.7.2 the software constructs the relationship network model of “disease-single drug-active ingredient-action target”. Protein protein interaction (PPI) network was constructed by using a string database. R4.1.1 software was used for GO function enrichment analysis and KEGG pathway enrichment analysis. Results: In this study, we obtained 158 active ingredients, 40 potential therapeutic targets, 74 GO projects, and 99 pathways. Major pathways include Lipid and atherosclerosis, Chemical carcinogenesis-receptor activation, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway in diabetic complications, Pathways of neurodegeneration-multiple diseases, etc. Conclusion: Xinyi San has the characteristics of multi-component, multi-target, and multi-channel in the treatment of senile rhinitis. This study provides a basis for the in-depth study of Xinyi San.
文摘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.
