Betalains are natural coloring pigments with betalamic acid as the core structure of all subclasses.Besides their coloring properties,betalains exhibit various biological activities,including antioxidant and anti-infl...Betalains are natural coloring pigments with betalamic acid as the core structure of all subclasses.Besides their coloring properties,betalains exhibit various biological activities,including antioxidant and anti-inflammatory properties,which are highly imperative.Further in-vivo studies reported that betalains protect various body organs,leading to health enhancement.Body organs,including the heart,liver,kidney,lung,etc.,are important for a healthy life.However,these organs can be affected or damaged by various stress factors,toxicants,and harmful substances.Recent studies have claimed that betalains could protect all vital organs of the body through antioxidant and anti-inflammatory mechanisms.This review article described the in-vivo antioxidant and anti-inflammatory activities of betalains in various cell-line or animal models.A comprehensive discussion has been provided on the mechanism of action of betalains in protecting various body organs,including cardio-protective effect,hepato-protective ability,renal protection capacity,repro-protective ability,neuro-protective effect,lung protection,and gut protection ability.Finally,future research directions and conclusions have been outlined.展开更多
Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diab...Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.展开更多
This review delves into the detrimental impact of alcohol consumption on internal organs and reproductive health,elucidating the underlying mechanisms involving the Toll-like receptor 4(TLR4)/Nuclear factor kappa ligh...This review delves into the detrimental impact of alcohol consumption on internal organs and reproductive health,elucidating the underlying mechanisms involving the Toll-like receptor 4(TLR4)/Nuclear factor kappa light chain enhancer of activated B cells(NF-kB)pathway and the Cytochrome P4502E1(CYP2E1)/reactive oxygen spe-cies(ROS)/nuclear factor erythroid 2-related factor 2(Nrf2)pathways.The TLR4/NF-kB pathway,crucial for inflammatory and immune responses,triggers the production of pro-inflammatory agents and type-1 interferon,disrupting the balance between inflammatory and antioxidant responses when tissues are chronically exposed to al-cohol.Alcohol-induced dysbiosis in gut microbes heightens gut wall permeability to pathogen-associated molecular patterns(PAMPs),leading to liver cell infection and subsequent inflammation.Concurrently,CYP2E1-mediated alcohol metabolism gen-erates ROS,causing oxidative stress and damaging cells,lipids,proteins,and deoxy-ribonucleic acid(DNA).To counteract this inflammatory imbalance,Nrf2 regulates gene expression,inhibiting inflammatory progression and promoting antioxidant re-sponses.Excessive alcohol intake results in elevated liver enzymes(ADH,CYP2E1,and catalase),ROS,NADH,acetaldehyde,and acetate,leading to damage in vital organs such as the heart,brain,and lungs.Moreover,alcohol negatively affects reproduc-tive health by inhibiting the hypothalamic-pituitary-gonadal axis,causing infertility in both men and women.These findings underscore the profound health concerns associated with alcohol-induced damage,emphasizing the need for public awareness regarding the intricate interplay between immune responses and the multi-organ im-pacts of alcohol consumption.展开更多
Valine is an essential amino acid and a type of branched-chain amino acid. Due to the involvement of branchedchain amino acids in various metabolic pathways, there has been a surge of interests in valine nutrition and...Valine is an essential amino acid and a type of branched-chain amino acid. Due to the involvement of branchedchain amino acids in various metabolic pathways, there has been a surge of interests in valine nutrition and its role in animal physiology. In pigs, the interactions between valine and other branched-chain amino acids or aromatic amino acids are complex. In this review, we delve into the interaction mechanism, metabolic pathways, and biological functions of valine. Appropriate valine supplementation not only enhances growth and reproductive performances, but also modulates gut microbiota and immune functions. Based on past observations and interpretations, we provide recommended feed levels of valine for weaned piglets, growing pigs, gilts, lactating sows, barrows and entire males. The summarized valine nutrient requirements for pigs at different stages offer valuable insights for future research and practical applications in animal husbandry.展开更多
Acute pancreatitis(AP)is a leading cause of gastrointestinal-related hospitalizations in the United States,resulting in 300000 admissions per year with an estimated cost of over$2.6 billion annually.The severity of AP...Acute pancreatitis(AP)is a leading cause of gastrointestinal-related hospitalizations in the United States,resulting in 300000 admissions per year with an estimated cost of over$2.6 billion annually.The severity of AP is determined by the presence of pancreatic complications and end-organ damage.While moderate/severe pancreatitis can be associated with significant morbidity and mortality,the majority of patients have a mild presentation with an uncomplicated course and mortality rate of less than 2%.Despite favorable outcomes,the majority of mild AP patients are admitted,contributing to healthcare cost and burden.In this Editorial we review the performance of an emergency department(ED)pathway for patients with mild AP at a tertiary care center with the goal of reducing hospitalizations,resource utilization,and costs after several years of implementation of the pathway.We discuss the clinical course and outcomes of mild AP patients enrolled in the pathway who were successfully discharged from the ED compared to those who were admitted to the hospital,and identify predictors of successful ED discharge to select patients who can potentially be triaged to the pathway.We conclude that by implementing innovative clinical pathways which are established and reproducible,selected AP patients can be safely discharged from the ED,reducing hospitalizations and healthcare costs,without compromising clinical outcomes.We also identify a subset of patients most likely to succeed in this pathway.展开更多
Dichloromethane(DCM)dehalogenase stands as a crucial enzyme implicated in the degradation of methylene chloride across diverse environmental and biological contexts.However,the unbinding pathways of ligands from DCM d...Dichloromethane(DCM)dehalogenase stands as a crucial enzyme implicated in the degradation of methylene chloride across diverse environmental and biological contexts.However,the unbinding pathways of ligands from DCM dehalogenase remain unexplored.In order to gain a deeper understanding of the binding sites and dissociation pathways of dichloromethane(DCM)and glutathione(GSH)from the DCM dehalogenase,random accelerated molecular dynamics(RAMD)simulations were performed,in which DCM and GSH were forced to leave the active site.The protein structure was predicted using Alphafold2,and the conformations of GSH and DCM in the binding pocket were predicted by docking.A long equilibrium simulation was conducted to validate the structure of the complex.The results show that GSH is most commonly observed in three main pathways,one of which is more important than the other two.In addition,DCM was observed to escape along a unique pathway.The key residues and protein helices of each pathway were identified.The results can provide a theoretical foundation for the subsequent dissociation mechanism of DCM dehalogenase.展开更多
Fructose and glucose are often widely used in food processing and may contribute to many metabolic diseases.To observe the effects of different doses of glucose and fructose on human metabolism and cellular communicat...Fructose and glucose are often widely used in food processing and may contribute to many metabolic diseases.To observe the effects of different doses of glucose and fructose on human metabolism and cellular communication,volunteers were given low,medium,and high doses of glucose and fructose.Serum cytokines,glucose,lactate,nicotinamide adenine dinucleotide(NADH)and metabolic enzymes were assayed,and central carbon metabolic pathway networks and cytokine communication networks were constructed.The results showed that the glucose and fructose groups basically maintained the trend of decreasing catabolism and increasing anabolism with increasing dose.Compared with glucose,low-dose fructose decreased catabolism and increased anabolism,significantly enhanced the expression of the inflammatory cytokine interferon-γ(IFN-γ),macrophage-derived chemokine(MDC),induced protein-10(IP-10),and eotaxin,and significantly reduced the activity of isocitrate dehydrogenase(ICDH)and pyruvate dehydrogenase complexes(PDHC).Both medium and high doses of fructose increase catabolism and anabolism,and there are more cytokines and enzymes with significant changes.Furthermore,multiple cytokines and enzymes show strong relevance to metabolic regulation by altering the transcription and expression of enzymes in central carbon metabolic pathways.Therefore,excessive intake of fructose should be reduced to avoid excessive inflammatory responses,allergic reactions and autoimmune diseases.展开更多
Background:Paclitaxel is a compound derived from Pacific yew bark that induces various cancer cell apoptosis.However,whether it also has anticancer activities in KOSC3 cells,an oral cancer cell line,is unclear.Methods:...Background:Paclitaxel is a compound derived from Pacific yew bark that induces various cancer cell apoptosis.However,whether it also has anticancer activities in KOSC3 cells,an oral cancer cell line,is unclear.Methods:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,flow cytometry,and western blotting assays were carried out to assess cell viability,subG1 phase of the cell cycle,and apoptosis-related protein expression,respectively.Results:Ourfindings indicate that paclitaxel could inhibit cell viability and increase the expression of apoptotic markers,including plasma membrane blebbing and the cleavage of poly ADP-ribose polymerase in KOSC3 cells.Also,the treatment with paclitaxel remarkably elevated the percentage of the subG1 phase in KOSC3 cells.In addition,treatment with a pan-caspase inhibitor could recover paclitaxel-inhibited cell viability.Moreover,caspase-8,caspase-9,caspase-7,and BH3 interacting domain death agonist(Bid)were activated in paclitaxel-treated KOSC3 cells.Conclusions:Paclitaxel induced apoptosis through caspase cascade in KOSC3 cells.展开更多
Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength.However,current anti-resorptive drugs carry a risk of various complications.The deep learning-based efficacy pre...Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength.However,current anti-resorptive drugs carry a risk of various complications.The deep learning-based efficacy prediction system(DLEPS)is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression changes.This study aimed to explore the protective effect and potential mechanisms of cinobufotalin(CB),a traditional Chinese medicine(TCM),on bone loss.Methods:DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary osteoporosis.Micro-CT,histological and morphological analysis were applied for the bone protective detection of CB,and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells(hBMMSCs)were also investigated.The underlying mechanism was verified using qRT-PCR,Western blot(WB),immunofluorescence(IF),etc.Results:A safe concentration(0.25mg/kg in vivo,0.05μM in vitro)of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of hBMMSCs.Both BMPs/SMAD and Wnt/β-catenin signaling pathways participated in CB-induced osteogenic differentiation,further regulating the expression of osteogenesis-associated factors,and ultimately promoting osteogenesis.Conclusion:Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss,further promoting osteogenic differentiation/function of hBMMSCs,with BMPs/SMAD and Wnt/β-catenin signaling pathways involved.展开更多
Background: Leprosy is known to cause disability that leads to severe outcomes like stigma, discrimination, mental health problems and participation restriction. Furthermore, in cases of infectious leprosy, longer del...Background: Leprosy is known to cause disability that leads to severe outcomes like stigma, discrimination, mental health problems and participation restriction. Furthermore, in cases of infectious leprosy, longer delays increase the risk for the spread of the disease. Despite being preventable and curable, a significant proportion of new leprosy patients (39%) in 2019 had grade 2 (Described as Visible disability) at the time of diagnosis signifying late presentation. The aim of this study was to describe patient journeys from first symptoms suggestive of leprosy to a diagnosis and individual and community level factors associated with health seeking behavior of leprosy patients. Methods: This was a cross-sectional explorative study implemented in Kasese, Mayuge and Yumbe districts .A structured questionnaire was used to collect quantitative data. Qualitative assessment included patients, family members, health workers, voluntary health teams and the district health team. Descriptive statistics were presented in terms of percentages, frequency tables, pie Charts and graphs for easy interpretation and discussion. Results: The results indicate that 53% of the respondents identified as female. The median age of the respondents being 34 years, with a range of 1 to 76 years (Mean: 44.7, Mode: 65, Standard-Deviation: 19.6, Kurtosis: 0.6). The most common first symptom noticed by respondents was skin lesions (65%) followed by deformities (18%) (P value = 0.05%) occurring mostly in the feet (P-value = 0.48). Majority (52%) of the patients had taken more than 24 months (SD 18.72 OR 2.75) for a diagnosis to be made with a maximum delay of over 60 months. The most common cause of delay in seeking health care was lack of knowledge on leprosy (P value=Conclusions: There was a delay of 2 years in seeking health care for the majority of the patients. Key barriers to early diagnosis were lack of knowledge and infrastructure. Community sensitization and strengthening capacity building are needed to achieve early diagnosis of leprosy and proper management.展开更多
BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therap...BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therapeutic effects and the possible mechanism of JPGS on DN.METHODS We first evaluated the therapeutic potential of JPGS on a DN mouse model.We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics.Furthermore,we examined the effects of JPGS on c-Jun N-terminal kinase(JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/NOD-like receptor family pyrin domain containing 3(NLRP3).RESULTS The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress.Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice.A total of 51 differential metabolites were screened.Pathway analysis results indicated that nine pathways significantly changed between the control and model groups,while six pathways significantly altered between the model and JPGS groups.Pathways related to cysteine and methionine metabolism;alanine,tryptophan metabolism;aspartate and glutamate metabolism;and riboflavin metabolism were identified as the key pathways through which JPGS affects DN.Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors.CONCLUSION JPGS could markedly treat mice with streptozotocin(STZ)-induced DN,which is possibly related to the regulation of several metabolic pathways found in kidneys.Furthermore,JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathwaymediated apoptosis in DN mice.展开更多
Cancer cell dormancy(CCD)in colorectal cancer(CRC)poses a significant challenge to effective treatment.In CRC,CCD contributes to tumour recurrence,drug resistance,and amplifying the disease's burden.The molecular ...Cancer cell dormancy(CCD)in colorectal cancer(CRC)poses a significant challenge to effective treatment.In CRC,CCD contributes to tumour recurrence,drug resistance,and amplifying the disease's burden.The molecular mechanisms governing CCD and strategies for eliminating dormant cancer cells remain largely unexplored.Therefore,understanding the molecular mechanisms governing dormancy is crucial for improving patient outcomes and developing targeted therapies.This editorial highlights the complex interplay of signalling pathways and factors involved in colorectal CCD,emphasizing the roles of Hippo/YAP,pluripotent transcription factors such as NANOG,HIF-1αsignalling,and Notch signalling pathways.Additionally,ERK/p38α/β/MAPK pathways,AKT signalling pathway,and Extracellular Matrix Metalloproteinase Inducer,along with some potential less explored pathways such as STAT/p53 switch and canonical and non-canonical Wnt and SMAD signalling,are also involved in promoting colorectal CCD.Highlighting their clinical significance,these findings may offer the potential for identifying key dormancy regulator pathways,improving treatment strategies,surmounting drug resistance,and advancing personalized medicine approaches.Moreover,insights into dormancy mechanisms could lead to the development of predictive biomarkers for identifying patients at risk of recurrence and the tailoring of targeted therapies based on individual dormancy profiles.It is essential to conduct further research into these pathways and their modulation to fully comprehend CRC dormancy mechanisms and enhance patient outcomes.展开更多
Background:Oral squamous cell carcinoma(OSCC)represents a prevalent malignancy in the oral and maxillofacial area,having a considerable negative impact on both the quality of life and overall survival of affected indi...Background:Oral squamous cell carcinoma(OSCC)represents a prevalent malignancy in the oral and maxillofacial area,having a considerable negative impact on both the quality of life and overall survival of affected individuals.Our research endeavors to leverage bioinformatic approaches to elucidate oncogenic signaling pathways,with the ultimate goal of gaining deeper insights into the molecular underpinnings of OSCC pathogenesis,and thus laying the groundwork for the development of more effective therapeutic and preventive strategies.Methods:Differential expression analysis was performed on mRNA data from tumor and normal tissue groups to identify genes associated with OSCC,using The Cancer Genome Atlas database.Predictions of oncogenic signaling pathways linked to differentially expressedmRNAs were made,and these results were presented visually using R software,using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichments.Results:GO and KEGG analyses of 2938 differentially expressed genes in OSCC highlighted their significant involvement in various biological processes.Notably,these processes were related to the extracellular matrix,structural organization,connective tissue development,and cell cycle regulation.Conclusions:The comprehensive exploration of gene expression patterns provides valuable insights into potential oncogenic mechanisms in OSCC.展开更多
Background:Radix Aconiti Lateralis Preparata(Fu-zi)is a traditional Chinese medicinal herb,which has been widely used in the clinic and has potent anti-inflammatory activities.we aimed to explore the mechanisms of ext...Background:Radix Aconiti Lateralis Preparata(Fu-zi)is a traditional Chinese medicinal herb,which has been widely used in the clinic and has potent anti-inflammatory activities.we aimed to explore the mechanisms of extract containing alkaloids from different Fu-zi Processed Products(FPP)in treating inflammation,especially rheumatoid arthritis(RA).Methods:Firstly,using network pharmacology technology,the ingredients,and targets of Fu-zi were obtained by searching and screening,the targets involving RA were acquired,the intersection targets were constructed a"component-target-pathway"network.A comprehensive investigation was conducted on the anti-rheumatoid arthritis mechanisms of 5 FPPs in lipopolysaccharide(LPS)induced RAW264.7 cells,which serve as a model for RA.The production of NO and inflammatory cytokines were measured by ELISA kit.Quantitative Real-time PCR(qRT-PCR)was utilized to measure the mRNA levels.COX-2/PGE2 signaling pathway-associated proteins were determined by western blot.Results:According to a network pharmacological study,16 chemical components and 43 common targets were found in Fu-zi and 6 key targets including PTGS2 were closely related to the mechanism of Fu-zi in treating RA.The in vitro study revealed that the levels of NO,TNF-α,and IL-1βwere substantially decreased by the 5 FPPs.The 5 FPPs significantly suppressed the expression of proteins COX-2,iNOS,and NF-κB,with particularly notable effects observed for PFZ and XFZ.Conclusion:Altogether,these results demonstrated that the 5 PPS containing alkaloids have a good anti-RA-related inflammatory effect,and the mechanism may be related to COX-2/PGE2 signaling pathway,particularly,Fu-zi prepared utilizing a traditional Chinese technique.展开更多
The number of students demanding computer science(CS)education is rapidly rising,and while faculty sizes are also growing,the traditional pipeline consisting of a CS major,a CS master’s,and then a move to industry or...The number of students demanding computer science(CS)education is rapidly rising,and while faculty sizes are also growing,the traditional pipeline consisting of a CS major,a CS master’s,and then a move to industry or a Ph.D.program is simply not scalable.To address this problem,the Department of Computing at the University of Illinois has introduced a multidisciplinary approach to computing,which is a scalable and collaborative approach to capitalize on the tremendous demand for computer science education.The key component of the approach is the blended major,also referred to as“CS+X”,where CS denotes computer science and X denotes a non-computing field.These CS+X blended degrees enable win-win partnerships among multiple subject areas,distributing the educational responsibilities while growing the entire university.To meet the demand from non-CS majors,another pathway that is offered is a graduate certificate program in addition to the traditional minor program.To accommodate the large number of students,scalable teaching tools,such as automatic graders,have also been developed.展开更多
In the strategic context of rural revitalization,optimizing the quality of agricultural statistical services is a crucial element for advancing agricultural modernization and sustainable rural economic development.Thi...In the strategic context of rural revitalization,optimizing the quality of agricultural statistical services is a crucial element for advancing agricultural modernization and sustainable rural economic development.This paper focuses on the significance of enhancing agricultural statistical service quality under the backdrop of rural revitalization.It addresses current issues such as inadequate implementation of agricultural statistical survey systems,an imperfect data quality control system,and a shortage of statistical service personnel.Proposals are made to improve the statistical survey system,enhance the data quality control framework,and strengthen personnel training.These pathways offer references for elevating the quality of agricultural statistical services and implementing the rural revitalization strategy in the new era.展开更多
Against the backdrop of rapid global economic development,the demand for education has gradually shifted from quantitative growth to qualitative improvement.Vocational education,higher education,and continuing educati...Against the backdrop of rapid global economic development,the demand for education has gradually shifted from quantitative growth to qualitative improvement.Vocational education,higher education,and continuing education are crucial components of China’s education system,each serving different educational functions.However,the collaborative innovation among these three types of education is still in the preliminary exploration stage,with issues such as scattered resources and imperfect coordination mechanisms.This paper systematically reviews relevant domestic and international research and practical experiences,thoroughly analyzes the pathways,models,and mechanisms of collaborative innovation among these three types of education,and proposes practical and operational suggestions based on the actual situation in Xuzhou City.The study finds that collaboration between vocational education,higher education,and continuing education through innovation not only enhances the overall efficiency of educational resources but also promotes regional economic development and social progress.On this basis,this paper proposes specific measures such as building an education resource-sharing platform,promoting a chain-based talent training system,strengthening policy and institutional guarantees,and improving incentive mechanisms,aiming to provide a reference for local education administrators and contribute to the innovative development of education in China.展开更多
This paper firstly analyses the due evaluation indexes of curriculum civics and politics in physical education of higher vocational colleges and,based on the indexes,puts forward suggestions to improve the quality of ...This paper firstly analyses the due evaluation indexes of curriculum civics and politics in physical education of higher vocational colleges and,based on the indexes,puts forward suggestions to improve the quality of teaching curriculum civics and politics in physical education of higher vocational colleges and universities in Chongqing.It involves maintaining steadfast adherence to professional attributes,unwavering commitment to Sanquan education,and thorough exploration of professional civics and political elements.This approach also entails supplementing extracurricular civics and political resources and utilizing a variety of methods such as contextual teaching and role-modeling to the fullest extent.At the same time,we increase the opportunities for civics and political practice inside and outside the classroom and develop teaching evaluation and assessment in civics and politics.展开更多
Glabridin is the main ingredient of hydrophobic fraction in licorice extract and has been shown to have anti-melanogenesis activity in skins.However,the underlying mechanism(s)remain not completely understood.The aim ...Glabridin is the main ingredient of hydrophobic fraction in licorice extract and has been shown to have anti-melanogenesis activity in skins.However,the underlying mechanism(s)remain not completely understood.The aim of this study is thus to elucidate the possible mechanisms related to the melanogenesis suppression by glabridin in cultured B16 murine melanoma cells and in UVA radiation induced hyperpigmentation model of BALB/c mice as well.Molecular docking simulations revealed that between catalytic core residues and the compound.The treatment by glabridin significantly downregulated both transcriptional and/or protein expression of melanogenesis-related factors including melanocyte stimulating hormone receptor(MC1R),microphthalmia-associated transcription factor(MITF),tyrosinase(TYR),TYR-related protein-1(TRP-1)and TRP-2 in B16 cells.Both PKA/MITF and MAPK/MITF signaling pathways were found to be involved in the suppression of melanogenesis by glabridin in B16 cells.Also in vivo glabridin therapy significantly reduced hyperpigmentation,epidermal thickening,roughness and inflammation induced by frequent UVA exposure in mice skins,thus beneficial for skin healthcare.These data further look insights into the molecular mechanisms of melanogenesis suppression by glabridin,rationalizing the application of the natural compound for skin healthcare.展开更多
Chaenomeles speciosa(Sweet)Nakai cultivated widely in temperate regions possesses anti-inflammatory properties,however,the underlying molecular mechanisms remain not fully understood.In this study,a purified phenolic ...Chaenomeles speciosa(Sweet)Nakai cultivated widely in temperate regions possesses anti-inflammatory properties,however,the underlying molecular mechanisms remain not fully understood.In this study,a purified phenolic extract of C.speciosa rich in chlorogenic acid,procyanidin B1 and catechin(determined by HPLC-Q-TOF-MS/MS)exhibited dose-dependent anti-inflammatory effects on lipopolysaccharide(LPS)-treated RAW264.7 macrophages.The extract at 30μg/mL was most potent and enabled most cells in normal morphology under LPS stimulation without causing cytotoxicity.The extract suppressed the levels of nitric oxide(NO),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and interleukin-1β(IL-1β),and the mRNA and protein expressions of nitric oxide synthase(iNOS)and cyclooxygenase-2(COX-2).The mechanisms underlying such anti-inflammatory actions included the regulation of phosphorylation of related proteins to monitor the expressions of inflammatory mediators and genes in the nuclear factor kappa-B(NF-κB)and mitogen-activated protein kinase(MAPK)signaling pathways.Therefore,the phenolic extract from C.speciosa is a desirable anti-inflammatory agent for inflammatory conditions to meet the rising demand for natural and cost-effective therapeutics.展开更多
文摘Betalains are natural coloring pigments with betalamic acid as the core structure of all subclasses.Besides their coloring properties,betalains exhibit various biological activities,including antioxidant and anti-inflammatory properties,which are highly imperative.Further in-vivo studies reported that betalains protect various body organs,leading to health enhancement.Body organs,including the heart,liver,kidney,lung,etc.,are important for a healthy life.However,these organs can be affected or damaged by various stress factors,toxicants,and harmful substances.Recent studies have claimed that betalains could protect all vital organs of the body through antioxidant and anti-inflammatory mechanisms.This review article described the in-vivo antioxidant and anti-inflammatory activities of betalains in various cell-line or animal models.A comprehensive discussion has been provided on the mechanism of action of betalains in protecting various body organs,including cardio-protective effect,hepato-protective ability,renal protection capacity,repro-protective ability,neuro-protective effect,lung protection,and gut protection ability.Finally,future research directions and conclusions have been outlined.
基金supported by the Projects of the National Key R&D Program of China,Nos.2021YFC2400803(to YO),2021YFC2400801(to YQ)the National Natural Science Foundation of China,Nos.82002290(to YQ),82072452(to YO),82272475(to YO)+5 种基金the Young Elite Scientist Sponsorship Program by Cast,No.YESS20200153(to YQ)the Sino-German Mobility Programme,No.M-0699(to YQ)the Excellent Youth Cultivation Program of Shanghai Sixth People’s Hospital,No.ynyq202201(to YQ)the Shanghai Sailing Program,No.20YF1436000(to YQ)the Medical Engineering Co-Project of University of Shanghai for Science and Technology,10-22-310-520(to YO)a grant from Shanghai Municipal Health Commission,No.202040399(to YO).
文摘Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.
基金supported by the Jeffrey Cheah School of Medicine and Health Sciences and the Library Resources,Monash University Malaysia
文摘This review delves into the detrimental impact of alcohol consumption on internal organs and reproductive health,elucidating the underlying mechanisms involving the Toll-like receptor 4(TLR4)/Nuclear factor kappa light chain enhancer of activated B cells(NF-kB)pathway and the Cytochrome P4502E1(CYP2E1)/reactive oxygen spe-cies(ROS)/nuclear factor erythroid 2-related factor 2(Nrf2)pathways.The TLR4/NF-kB pathway,crucial for inflammatory and immune responses,triggers the production of pro-inflammatory agents and type-1 interferon,disrupting the balance between inflammatory and antioxidant responses when tissues are chronically exposed to al-cohol.Alcohol-induced dysbiosis in gut microbes heightens gut wall permeability to pathogen-associated molecular patterns(PAMPs),leading to liver cell infection and subsequent inflammation.Concurrently,CYP2E1-mediated alcohol metabolism gen-erates ROS,causing oxidative stress and damaging cells,lipids,proteins,and deoxy-ribonucleic acid(DNA).To counteract this inflammatory imbalance,Nrf2 regulates gene expression,inhibiting inflammatory progression and promoting antioxidant re-sponses.Excessive alcohol intake results in elevated liver enzymes(ADH,CYP2E1,and catalase),ROS,NADH,acetaldehyde,and acetate,leading to damage in vital organs such as the heart,brain,and lungs.Moreover,alcohol negatively affects reproduc-tive health by inhibiting the hypothalamic-pituitary-gonadal axis,causing infertility in both men and women.These findings underscore the profound health concerns associated with alcohol-induced damage,emphasizing the need for public awareness regarding the intricate interplay between immune responses and the multi-organ im-pacts of alcohol consumption.
基金supported by Postdoctoral Innovation Talents’ Support Programthe National Natural Science Foundation of China (32130099)+1 种基金the Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project (TSBICIP-CXRC-038)Laboratory of Lingnan Modern Agriculture Project (NT2021005)。
文摘Valine is an essential amino acid and a type of branched-chain amino acid. Due to the involvement of branchedchain amino acids in various metabolic pathways, there has been a surge of interests in valine nutrition and its role in animal physiology. In pigs, the interactions between valine and other branched-chain amino acids or aromatic amino acids are complex. In this review, we delve into the interaction mechanism, metabolic pathways, and biological functions of valine. Appropriate valine supplementation not only enhances growth and reproductive performances, but also modulates gut microbiota and immune functions. Based on past observations and interpretations, we provide recommended feed levels of valine for weaned piglets, growing pigs, gilts, lactating sows, barrows and entire males. The summarized valine nutrient requirements for pigs at different stages offer valuable insights for future research and practical applications in animal husbandry.
文摘Acute pancreatitis(AP)is a leading cause of gastrointestinal-related hospitalizations in the United States,resulting in 300000 admissions per year with an estimated cost of over$2.6 billion annually.The severity of AP is determined by the presence of pancreatic complications and end-organ damage.While moderate/severe pancreatitis can be associated with significant morbidity and mortality,the majority of patients have a mild presentation with an uncomplicated course and mortality rate of less than 2%.Despite favorable outcomes,the majority of mild AP patients are admitted,contributing to healthcare cost and burden.In this Editorial we review the performance of an emergency department(ED)pathway for patients with mild AP at a tertiary care center with the goal of reducing hospitalizations,resource utilization,and costs after several years of implementation of the pathway.We discuss the clinical course and outcomes of mild AP patients enrolled in the pathway who were successfully discharged from the ED compared to those who were admitted to the hospital,and identify predictors of successful ED discharge to select patients who can potentially be triaged to the pathway.We conclude that by implementing innovative clinical pathways which are established and reproducible,selected AP patients can be safely discharged from the ED,reducing hospitalizations and healthcare costs,without compromising clinical outcomes.We also identify a subset of patients most likely to succeed in this pathway.
基金National Natural Science Foundation of China(22073030)the Oriental Scholars of Shanghai Universities。
文摘Dichloromethane(DCM)dehalogenase stands as a crucial enzyme implicated in the degradation of methylene chloride across diverse environmental and biological contexts.However,the unbinding pathways of ligands from DCM dehalogenase remain unexplored.In order to gain a deeper understanding of the binding sites and dissociation pathways of dichloromethane(DCM)and glutathione(GSH)from the DCM dehalogenase,random accelerated molecular dynamics(RAMD)simulations were performed,in which DCM and GSH were forced to leave the active site.The protein structure was predicted using Alphafold2,and the conformations of GSH and DCM in the binding pocket were predicted by docking.A long equilibrium simulation was conducted to validate the structure of the complex.The results show that GSH is most commonly observed in three main pathways,one of which is more important than the other two.In addition,DCM was observed to escape along a unique pathway.The key residues and protein helices of each pathway were identified.The results can provide a theoretical foundation for the subsequent dissociation mechanism of DCM dehalogenase.
基金financially supported by National Natural Science Foundation of China(31901782)。
文摘Fructose and glucose are often widely used in food processing and may contribute to many metabolic diseases.To observe the effects of different doses of glucose and fructose on human metabolism and cellular communication,volunteers were given low,medium,and high doses of glucose and fructose.Serum cytokines,glucose,lactate,nicotinamide adenine dinucleotide(NADH)and metabolic enzymes were assayed,and central carbon metabolic pathway networks and cytokine communication networks were constructed.The results showed that the glucose and fructose groups basically maintained the trend of decreasing catabolism and increasing anabolism with increasing dose.Compared with glucose,low-dose fructose decreased catabolism and increased anabolism,significantly enhanced the expression of the inflammatory cytokine interferon-γ(IFN-γ),macrophage-derived chemokine(MDC),induced protein-10(IP-10),and eotaxin,and significantly reduced the activity of isocitrate dehydrogenase(ICDH)and pyruvate dehydrogenase complexes(PDHC).Both medium and high doses of fructose increase catabolism and anabolism,and there are more cytokines and enzymes with significant changes.Furthermore,multiple cytokines and enzymes show strong relevance to metabolic regulation by altering the transcription and expression of enzymes in central carbon metabolic pathways.Therefore,excessive intake of fructose should be reduced to avoid excessive inflammatory responses,allergic reactions and autoimmune diseases.
基金The present study was supported by the National Science and Technology Council,Taiwan(MOST-107-2320-B-471-001 to YYL and MOST-110-2320-B-006-025-MY3 to BMH)by An Nan Hospital(ANHRF111-55 to TCC and BMH).
文摘Background:Paclitaxel is a compound derived from Pacific yew bark that induces various cancer cell apoptosis.However,whether it also has anticancer activities in KOSC3 cells,an oral cancer cell line,is unclear.Methods:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,flow cytometry,and western blotting assays were carried out to assess cell viability,subG1 phase of the cell cycle,and apoptosis-related protein expression,respectively.Results:Ourfindings indicate that paclitaxel could inhibit cell viability and increase the expression of apoptotic markers,including plasma membrane blebbing and the cleavage of poly ADP-ribose polymerase in KOSC3 cells.Also,the treatment with paclitaxel remarkably elevated the percentage of the subG1 phase in KOSC3 cells.In addition,treatment with a pan-caspase inhibitor could recover paclitaxel-inhibited cell viability.Moreover,caspase-8,caspase-9,caspase-7,and BH3 interacting domain death agonist(Bid)were activated in paclitaxel-treated KOSC3 cells.Conclusions:Paclitaxel induced apoptosis through caspase cascade in KOSC3 cells.
基金Beijing Natural Science Foundation,Grant/Award Number:L222145 and L222030Emerging Engineering Interdisciplinary Project and the Fundamental Research Funds for the Central Universities,Grant/Award Number:PKU2022XGK008Peking University Medicine Fund of Fostering Young Scholars’Scientific&Technological Innovation,Grant/Award Number:BMU2022PY010。
文摘Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength.However,current anti-resorptive drugs carry a risk of various complications.The deep learning-based efficacy prediction system(DLEPS)is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression changes.This study aimed to explore the protective effect and potential mechanisms of cinobufotalin(CB),a traditional Chinese medicine(TCM),on bone loss.Methods:DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary osteoporosis.Micro-CT,histological and morphological analysis were applied for the bone protective detection of CB,and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells(hBMMSCs)were also investigated.The underlying mechanism was verified using qRT-PCR,Western blot(WB),immunofluorescence(IF),etc.Results:A safe concentration(0.25mg/kg in vivo,0.05μM in vitro)of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of hBMMSCs.Both BMPs/SMAD and Wnt/β-catenin signaling pathways participated in CB-induced osteogenic differentiation,further regulating the expression of osteogenesis-associated factors,and ultimately promoting osteogenesis.Conclusion:Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss,further promoting osteogenic differentiation/function of hBMMSCs,with BMPs/SMAD and Wnt/β-catenin signaling pathways involved.
文摘Background: Leprosy is known to cause disability that leads to severe outcomes like stigma, discrimination, mental health problems and participation restriction. Furthermore, in cases of infectious leprosy, longer delays increase the risk for the spread of the disease. Despite being preventable and curable, a significant proportion of new leprosy patients (39%) in 2019 had grade 2 (Described as Visible disability) at the time of diagnosis signifying late presentation. The aim of this study was to describe patient journeys from first symptoms suggestive of leprosy to a diagnosis and individual and community level factors associated with health seeking behavior of leprosy patients. Methods: This was a cross-sectional explorative study implemented in Kasese, Mayuge and Yumbe districts .A structured questionnaire was used to collect quantitative data. Qualitative assessment included patients, family members, health workers, voluntary health teams and the district health team. Descriptive statistics were presented in terms of percentages, frequency tables, pie Charts and graphs for easy interpretation and discussion. Results: The results indicate that 53% of the respondents identified as female. The median age of the respondents being 34 years, with a range of 1 to 76 years (Mean: 44.7, Mode: 65, Standard-Deviation: 19.6, Kurtosis: 0.6). The most common first symptom noticed by respondents was skin lesions (65%) followed by deformities (18%) (P value = 0.05%) occurring mostly in the feet (P-value = 0.48). Majority (52%) of the patients had taken more than 24 months (SD 18.72 OR 2.75) for a diagnosis to be made with a maximum delay of over 60 months. The most common cause of delay in seeking health care was lack of knowledge on leprosy (P value=Conclusions: There was a delay of 2 years in seeking health care for the majority of the patients. Key barriers to early diagnosis were lack of knowledge and infrastructure. Community sensitization and strengthening capacity building are needed to achieve early diagnosis of leprosy and proper management.
基金Supported by the Scientific Foundation of Administration of Traditional Chinese Medicine of Hebei Province,China,No.2023257.
文摘BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therapeutic effects and the possible mechanism of JPGS on DN.METHODS We first evaluated the therapeutic potential of JPGS on a DN mouse model.We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics.Furthermore,we examined the effects of JPGS on c-Jun N-terminal kinase(JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/NOD-like receptor family pyrin domain containing 3(NLRP3).RESULTS The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress.Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice.A total of 51 differential metabolites were screened.Pathway analysis results indicated that nine pathways significantly changed between the control and model groups,while six pathways significantly altered between the model and JPGS groups.Pathways related to cysteine and methionine metabolism;alanine,tryptophan metabolism;aspartate and glutamate metabolism;and riboflavin metabolism were identified as the key pathways through which JPGS affects DN.Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors.CONCLUSION JPGS could markedly treat mice with streptozotocin(STZ)-induced DN,which is possibly related to the regulation of several metabolic pathways found in kidneys.Furthermore,JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathwaymediated apoptosis in DN mice.
文摘Cancer cell dormancy(CCD)in colorectal cancer(CRC)poses a significant challenge to effective treatment.In CRC,CCD contributes to tumour recurrence,drug resistance,and amplifying the disease's burden.The molecular mechanisms governing CCD and strategies for eliminating dormant cancer cells remain largely unexplored.Therefore,understanding the molecular mechanisms governing dormancy is crucial for improving patient outcomes and developing targeted therapies.This editorial highlights the complex interplay of signalling pathways and factors involved in colorectal CCD,emphasizing the roles of Hippo/YAP,pluripotent transcription factors such as NANOG,HIF-1αsignalling,and Notch signalling pathways.Additionally,ERK/p38α/β/MAPK pathways,AKT signalling pathway,and Extracellular Matrix Metalloproteinase Inducer,along with some potential less explored pathways such as STAT/p53 switch and canonical and non-canonical Wnt and SMAD signalling,are also involved in promoting colorectal CCD.Highlighting their clinical significance,these findings may offer the potential for identifying key dormancy regulator pathways,improving treatment strategies,surmounting drug resistance,and advancing personalized medicine approaches.Moreover,insights into dormancy mechanisms could lead to the development of predictive biomarkers for identifying patients at risk of recurrence and the tailoring of targeted therapies based on individual dormancy profiles.It is essential to conduct further research into these pathways and their modulation to fully comprehend CRC dormancy mechanisms and enhance patient outcomes.
文摘Background:Oral squamous cell carcinoma(OSCC)represents a prevalent malignancy in the oral and maxillofacial area,having a considerable negative impact on both the quality of life and overall survival of affected individuals.Our research endeavors to leverage bioinformatic approaches to elucidate oncogenic signaling pathways,with the ultimate goal of gaining deeper insights into the molecular underpinnings of OSCC pathogenesis,and thus laying the groundwork for the development of more effective therapeutic and preventive strategies.Methods:Differential expression analysis was performed on mRNA data from tumor and normal tissue groups to identify genes associated with OSCC,using The Cancer Genome Atlas database.Predictions of oncogenic signaling pathways linked to differentially expressedmRNAs were made,and these results were presented visually using R software,using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichments.Results:GO and KEGG analyses of 2938 differentially expressed genes in OSCC highlighted their significant involvement in various biological processes.Notably,these processes were related to the extracellular matrix,structural organization,connective tissue development,and cell cycle regulation.Conclusions:The comprehensive exploration of gene expression patterns provides valuable insights into potential oncogenic mechanisms in OSCC.
基金supported by Sichuan Province Science and Technology Support Program(NO.2020JDJQ0063,NO.2020YFS0566 and NO.2021JDKY0037,A-2021N-Z-5).
文摘Background:Radix Aconiti Lateralis Preparata(Fu-zi)is a traditional Chinese medicinal herb,which has been widely used in the clinic and has potent anti-inflammatory activities.we aimed to explore the mechanisms of extract containing alkaloids from different Fu-zi Processed Products(FPP)in treating inflammation,especially rheumatoid arthritis(RA).Methods:Firstly,using network pharmacology technology,the ingredients,and targets of Fu-zi were obtained by searching and screening,the targets involving RA were acquired,the intersection targets were constructed a"component-target-pathway"network.A comprehensive investigation was conducted on the anti-rheumatoid arthritis mechanisms of 5 FPPs in lipopolysaccharide(LPS)induced RAW264.7 cells,which serve as a model for RA.The production of NO and inflammatory cytokines were measured by ELISA kit.Quantitative Real-time PCR(qRT-PCR)was utilized to measure the mRNA levels.COX-2/PGE2 signaling pathway-associated proteins were determined by western blot.Results:According to a network pharmacological study,16 chemical components and 43 common targets were found in Fu-zi and 6 key targets including PTGS2 were closely related to the mechanism of Fu-zi in treating RA.The in vitro study revealed that the levels of NO,TNF-α,and IL-1βwere substantially decreased by the 5 FPPs.The 5 FPPs significantly suppressed the expression of proteins COX-2,iNOS,and NF-κB,with particularly notable effects observed for PFZ and XFZ.Conclusion:Altogether,these results demonstrated that the 5 PPS containing alkaloids have a good anti-RA-related inflammatory effect,and the mechanism may be related to COX-2/PGE2 signaling pathway,particularly,Fu-zi prepared utilizing a traditional Chinese technique.
文摘The number of students demanding computer science(CS)education is rapidly rising,and while faculty sizes are also growing,the traditional pipeline consisting of a CS major,a CS master’s,and then a move to industry or a Ph.D.program is simply not scalable.To address this problem,the Department of Computing at the University of Illinois has introduced a multidisciplinary approach to computing,which is a scalable and collaborative approach to capitalize on the tremendous demand for computer science education.The key component of the approach is the blended major,also referred to as“CS+X”,where CS denotes computer science and X denotes a non-computing field.These CS+X blended degrees enable win-win partnerships among multiple subject areas,distributing the educational responsibilities while growing the entire university.To meet the demand from non-CS majors,another pathway that is offered is a graduate certificate program in addition to the traditional minor program.To accommodate the large number of students,scalable teaching tools,such as automatic graders,have also been developed.
文摘In the strategic context of rural revitalization,optimizing the quality of agricultural statistical services is a crucial element for advancing agricultural modernization and sustainable rural economic development.This paper focuses on the significance of enhancing agricultural statistical service quality under the backdrop of rural revitalization.It addresses current issues such as inadequate implementation of agricultural statistical survey systems,an imperfect data quality control system,and a shortage of statistical service personnel.Proposals are made to improve the statistical survey system,enhance the data quality control framework,and strengthen personnel training.These pathways offer references for elevating the quality of agricultural statistical services and implementing the rural revitalization strategy in the new era.
文摘Against the backdrop of rapid global economic development,the demand for education has gradually shifted from quantitative growth to qualitative improvement.Vocational education,higher education,and continuing education are crucial components of China’s education system,each serving different educational functions.However,the collaborative innovation among these three types of education is still in the preliminary exploration stage,with issues such as scattered resources and imperfect coordination mechanisms.This paper systematically reviews relevant domestic and international research and practical experiences,thoroughly analyzes the pathways,models,and mechanisms of collaborative innovation among these three types of education,and proposes practical and operational suggestions based on the actual situation in Xuzhou City.The study finds that collaboration between vocational education,higher education,and continuing education through innovation not only enhances the overall efficiency of educational resources but also promotes regional economic development and social progress.On this basis,this paper proposes specific measures such as building an education resource-sharing platform,promoting a chain-based talent training system,strengthening policy and institutional guarantees,and improving incentive mechanisms,aiming to provide a reference for local education administrators and contribute to the innovative development of education in China.
基金Chongqing Vocational Education Teaching Reform Research Project(Z233371S)。
文摘This paper firstly analyses the due evaluation indexes of curriculum civics and politics in physical education of higher vocational colleges and,based on the indexes,puts forward suggestions to improve the quality of teaching curriculum civics and politics in physical education of higher vocational colleges and universities in Chongqing.It involves maintaining steadfast adherence to professional attributes,unwavering commitment to Sanquan education,and thorough exploration of professional civics and political elements.This approach also entails supplementing extracurricular civics and political resources and utilizing a variety of methods such as contextual teaching and role-modeling to the fullest extent.At the same time,we increase the opportunities for civics and political practice inside and outside the classroom and develop teaching evaluation and assessment in civics and politics.
基金supported by the Inner Mongolia Autonomous Region Science and Technology Revitalization Foundation (2021CG0029)the National Natural Science Foundation of China (22178070)
文摘Glabridin is the main ingredient of hydrophobic fraction in licorice extract and has been shown to have anti-melanogenesis activity in skins.However,the underlying mechanism(s)remain not completely understood.The aim of this study is thus to elucidate the possible mechanisms related to the melanogenesis suppression by glabridin in cultured B16 murine melanoma cells and in UVA radiation induced hyperpigmentation model of BALB/c mice as well.Molecular docking simulations revealed that between catalytic core residues and the compound.The treatment by glabridin significantly downregulated both transcriptional and/or protein expression of melanogenesis-related factors including melanocyte stimulating hormone receptor(MC1R),microphthalmia-associated transcription factor(MITF),tyrosinase(TYR),TYR-related protein-1(TRP-1)and TRP-2 in B16 cells.Both PKA/MITF and MAPK/MITF signaling pathways were found to be involved in the suppression of melanogenesis by glabridin in B16 cells.Also in vivo glabridin therapy significantly reduced hyperpigmentation,epidermal thickening,roughness and inflammation induced by frequent UVA exposure in mice skins,thus beneficial for skin healthcare.These data further look insights into the molecular mechanisms of melanogenesis suppression by glabridin,rationalizing the application of the natural compound for skin healthcare.
基金supported by the Key R&D Program of Forestry Shandong Province(2021TZXD014)the Science and Technology Innovation Breakthrough Project of Heze Ctiy(2021KJTP10).
文摘Chaenomeles speciosa(Sweet)Nakai cultivated widely in temperate regions possesses anti-inflammatory properties,however,the underlying molecular mechanisms remain not fully understood.In this study,a purified phenolic extract of C.speciosa rich in chlorogenic acid,procyanidin B1 and catechin(determined by HPLC-Q-TOF-MS/MS)exhibited dose-dependent anti-inflammatory effects on lipopolysaccharide(LPS)-treated RAW264.7 macrophages.The extract at 30μg/mL was most potent and enabled most cells in normal morphology under LPS stimulation without causing cytotoxicity.The extract suppressed the levels of nitric oxide(NO),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and interleukin-1β(IL-1β),and the mRNA and protein expressions of nitric oxide synthase(iNOS)and cyclooxygenase-2(COX-2).The mechanisms underlying such anti-inflammatory actions included the regulation of phosphorylation of related proteins to monitor the expressions of inflammatory mediators and genes in the nuclear factor kappa-B(NF-κB)and mitogen-activated protein kinase(MAPK)signaling pathways.Therefore,the phenolic extract from C.speciosa is a desirable anti-inflammatory agent for inflammatory conditions to meet the rising demand for natural and cost-effective therapeutics.