Alzheimer's disease(AD) is a progressive and degenerative neurological disease characterized by the deterioration of cognitive functions. While a definitive cure and optimal medication to impede disease progressio...Alzheimer's disease(AD) is a progressive and degenerative neurological disease characterized by the deterioration of cognitive functions. While a definitive cure and optimal medication to impede disease progression are currently unavailable, a plethora of studies have highlighted the potential advantages of exercise rehabilitation for managing this condition. Those studies show that exercise rehabilitation can enhance cognitive function and improve the quality of life for individuals affected by AD. Therefore, exercise rehabilitation has been regarded as one of the most important strategies for managing patients with AD. Herein, we provide a comprehensive analysis of the currently available findings on exercise rehabilitation in patients with AD, with a focus on the exercise types which have shown efficacy when implemented alone or combined with other treatment methods, as well as the potential mechanisms underlying these positive effects. Specifically, we explain how exercise may improve the brain microenvironment and neuronal plasticity. In conclusion, exercise is a cost-effective intervention to enhance cognitive performance and improve quality of life in patients with mild to moderate cognitive dysfunction. Therefore, it can potentially become both a physical activity and a tailored intervention. This review may aid the development of more effective and individualized treatment strategies to address the challenges imposed by this debilitating disease, especially in low-and middle-income countries.展开更多
Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced functionality.Mutation or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenes...Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced functionality.Mutation or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenesis can result in different types of ribosomopathies in clinic,collectively known as ribosomopathy genes.Emerging data suggest that ribosomopathy patients exhibit a significantly heightened susceptibility to cancer.Abnormal ribosome biogenesis and dysregulation of some ribosomopathy genes have also been found to be intimately associated with cancer development.The correlation between ribosome biogenesis or ribosomopathy and the development of malignancies has been well established.This work aims to review the recent advances in the research of ribosomopathy genes among human cancers and meanwhile,to excavate the potential role of these genes,which have not or rarely been reported in cancer,in the disease development across cancers.We plan to establish a theoretical framework between the ribosomopathy gene and cancer development,to further facilitate the potential of these genes as diagnostic biomarker as well as pharmaceutical targets for cancer treatment.展开更多
BACKGROUND The efficacy of mesenchymal stem cells(MSCs)in treating liver fibrosis has been demonstrated in several clinical studies.However,their low survival and liver implantation rates remain problematic.In recent ...BACKGROUND The efficacy of mesenchymal stem cells(MSCs)in treating liver fibrosis has been demonstrated in several clinical studies.However,their low survival and liver implantation rates remain problematic.In recent years,a large number of studies in animal models of liver fibrosis have shown that MSCs combined with drugs can improve the efficacy of MSCs in the treatment of liver fibrosis alone and inhibit its progression to end-stage liver disease.This has inspired new ways of thinking about treating liver fibrosis.AIM To investigate the effectiveness and mechanisms of MSCs combined with drugs in treating liver fibrosis.METHODS Data sources included four electronic databases and were constructed until January 2024.The subjects,interventions,comparators,outcomes,and study design principle were used to screen the literature,and the quality of the literature was evaluated to assess the risk of bias.Relevant randomised controlled trials were selected,and the final 13 studies were included in the final study.RESULTS A total of 13 studies were included after screening.Pooled analysis showed that MSCs combined with drug therapy significantly improved liver function,promoted the repair of damaged liver tissues,reduced the level of liver fibrosis-related indexes,and effectively ameliorated hepatic fibrosis by modulating the hepatic inflammatory microenvironment,promoting the homing of MSCs,and regulating the relevant signaling pathways,and the treatment efficacy was superior to MSCs alone.However,the combined treatment statistics showed no amelioration in serum albumin levels(standardized mean difference=0.77,95%confidence interval:-0.13 to 1.68,P=0.09).CONCLUSION In conclusion,MSCs combined with drugs for treating liver fibrosis effectively make up for the shortcomings of MSCs in their therapeutic effects.However,due to the different drugs,the treatment mechanism and effect also differ.Therefore,more randomized controlled trials are needed to compare the therapeutic efficacy of different drugs in combination with MSCs,aiming to select the“best companion”of MSCs in treating hepatic fibrosis.展开更多
BACKGROUND Psychological intervention nursing(PIN)has been considered to have a curative effect on cesarean section(CS)post-operative recovery.However,the therapeutic mechanisms remain obscure.AIM To explore the effec...BACKGROUND Psychological intervention nursing(PIN)has been considered to have a curative effect on cesarean section(CS)post-operative recovery.However,the therapeutic mechanisms remain obscure.AIM To explore the effects of PIN combined with acupressure massage on CS postoperative recovery.METHODS A retrospective study was conducted on 150 pregnant women admitted to an obstetrics department between January 2020 and January 2023.The control group(CG)received acupressure therapy(n=73),and the intervention group(IG)received acupressure therapy and PIN therapy(n=77).Postoperative recovery time was assessed by anal-exhausting,defecation,bed activity,breastfeeding,and hospital stay times.Adverse effects,including infection,bleeding,limb numbness,intrauterine hematoma,urinary retention,and venous thromboembolism,were recorded.the pain visual analogue scale(VAS)was used to evaluate the degree of pain.Anxiety and depression status were qualitatively assessed using the selfrating anxiety scale(SAS),self-rating depression scale(SDS),and Edinburgh postpartum depression scale(EPDS).The Pittsburgh sleep quality index(PSQI)was used to compare sleep quality between the groups.RESULTS The baseline data and SAS,SDS,EPDS,and PSQI scores did not significantly differ before CS(P>0.05)and neither did complication rates between the two groups after CS(P>0.05).However,anal-exhausting,defecation,waking up,breastfeeding,and hospitalization times were significantly shorter for participants in the IG than those for participants in the CG(P<0.05).The VAS,SAS,SDS,EPDS,and PSQI scores of the IG were significantly lower than those of the CG(P<0.05).CONCLUSION PIN,combined with acupressure massage,effectively promotes maternal recovery,reduces post-CS pain,and improves post-operative negative emotions and sleeping quality.展开更多
Weak redox ability and severe charge recombination pose significant obstacles to the advancement of CO_(2) photoreduction.To tackle this challenge and enhance the CO_(2) photoconversion efficiency,fabricating well-mat...Weak redox ability and severe charge recombination pose significant obstacles to the advancement of CO_(2) photoreduction.To tackle this challenge and enhance the CO_(2) photoconversion efficiency,fabricating well-matched S-scheme heterostructure and establishing a robust built-in electric field emerge as pivotal strategies.In pursuit of this goal,a core-shell structured CuInS_(2)@CoS_(2)S-scheme heterojunction was meticulously engineered through a two-step molten salt method.This approach over the CuInS_(2)-based composites produced an internal electric field owing to the disparity be-tween the Fermi levels of CoS_(2) and CuInS_(2) at their interface.Consequently,the electric field facili-tated the directed migration of charges and the proficient separation of photoinduced carriers.The resulting CuInS_(2)@CoS_(2) heterostructure exhibited remarkable CO_(2) photoreduction performance,which was 21.7 and 26.5 times that of pure CuInS_(2) and CoS_(2),respectively.The S-scheme heterojunc-tion photogenerated charge transfer mechanism was validated through a series of rigorous anal-yses,including in situ irradiation X-ray photoelectron spectroscopy,work function calculations,and differential charge density examinations.Furthermore,in situ infrared spectroscopy and density functional theory calculations corroborated the fact that the CuInS_(2)@CoS_(2) heterojunction substan-tially lowered the formation energy of *COOH and *CO.This study demonstrates the application potential of S-scheme heterojunctions fabricated via the molten salt method in the realm of ad-dressing carbon-related environmental issues.展开更多
Non-alcoholic fatty liver disease(NAFLD)poses a significant health challenge in modern societies due to shifts in lifestyle and dietary habits.Its complexity stems from genetic predisposition,environmental influences,...Non-alcoholic fatty liver disease(NAFLD)poses a significant health challenge in modern societies due to shifts in lifestyle and dietary habits.Its complexity stems from genetic predisposition,environmental influences,and metabolic factors.Epigenetic processes govern various cellular functions such as transcription,chromatin structure,and cell division.In NAFLD,these epigenetic tendencies,especially the process of histone methylation,are intricately intertwined with fat accumulation in the liver.Histone methylation is regulated by different enzymes like methyltransferases and demethylases and influences the expression of genes related to adipogenesis.While early-stage NAFLD is reversible,its progression to severe stages becomes almost irreversible.Therefore,early detection and intervention in NAFLD are crucial,and understanding the precise role of histone methylation in the early stages of NAFLD could be vital in halting or potentially reversing the progression of this disease.展开更多
BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value...BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.METHODS This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April 2007.Patients were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)staining.The expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients.Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015.The relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient.The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival analysis.RESULTS TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous tissue.The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multivariate analysis indicated that high expression of pSMAD3L(S204)and VEGFR-1 were independent risk factors for prognosis in GC patients.VEGFR-1 protein expression was correlated with TGF-β1(r=0.220,P=0.029),pSMAD3C(S423/425)(r=0.302,P=0.002),and pSMAD3L(S204)(r=0.201,P=0.047),respectively.Simultaneous overexpression of pSMAD3L(S204)and VEGFR-1 was associated with poor OS in gastric cancer patients.CONCLUSION Co-upregulation of pSMAD3L(S204)and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis,and pSMAD3L(204)may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.展开更多
BACKGROUND Eccrine porocarcinoma(EPC)is a rare skin tumor that mainly affects the elderly population.Tumors often present with slow growth and a good prognosis.EPCs are usually distinguished from other skin tumors usi...BACKGROUND Eccrine porocarcinoma(EPC)is a rare skin tumor that mainly affects the elderly population.Tumors often present with slow growth and a good prognosis.EPCs are usually distinguished from other skin tumors using histopathology and immunohistochemistry.However,surgical management alone may be inadequate if the tumor has metastasized.However,currently,surgical resection is the most commonly used treatment modality.CASE SUMMARY A seventy-four-year-old woman presented with a slow-growing nodule in her left temporal area,with no obvious itching or pain,for more than four months.Histopathological examination showed small columnar and short spindle-shaped cells;thus,basal cell carcinoma was suspected.However,immunohistochemical analysis revealed the expression of cytokeratin 5/6,p63 protein,p16 protein,and Ki-67 antigen(40%),and EPC was taken into consideration.The skin biopsy was repeated,and hematoxylin and eosin staining revealed ductal differentiation in some cells.Finally,the patient was diagnosed with EPC,and Mohs micrographic surgery was performed.We adapted follow-up visits in a year and not found any recurrence of nodules.CONCLUSION This case report emphasizes the diagnosis and differentiation of EPC.展开更多
Objective:Celastrol is a pentacyclic triterpenoid extracted from the traditional Chinese medicinal herb,Tripterygium wilfordii.This study aims to provide a scientific basis for the rational development and use of cela...Objective:Celastrol is a pentacyclic triterpenoid extracted from the traditional Chinese medicinal herb,Tripterygium wilfordii.This study aims to provide a scientific basis for the rational development and use of celastrol in breast cancer.Method:A quantitative chemical biology approach was used to investigate the protein targets and molecular mechanisms of celastrol in breast cancer cells.Results:Low-concentration celastrol exerted an anti-tumor effect by directly binding to hydroxysteroid dehydrogenase-like 2(HSDL2)and inhibiting its expression.Moreover,the expression of the pro-apoptotic protein,Bcl-2-associated X(BaX),increased,the level of the anti-apoptotic protein,B-cell lymphoma-2(Bcl-2),decreased,and the rate of apoptosis increased.After the transfection of cells with si-HSDL2,the apoptosis rate was similar to that observed after the administration of celastrol.However,apoptosis was reversed by the overexpression of HSDL2.Furthermore,our mass spectrometry(MS)data indicated a relationship between HSDL2 and the mitogen-activated protein kinase(MAPK)signaling pathway.We also found that the expression of HSDL2 was directly related to the degree of extracellular signal-regulated kinase(ERK)phosphorylation.Conclusion:Celastrol may promote apoptosis by suppressing the HSDL2/MAPK/ERK signaling pathway.展开更多
Background:Lotus seedpod(Receptaculum Nelumbinis)is the abundant by-products produced during lotus seed processing,and the sources are usually considered to be wastes and are abandoned outdoors or incinerated.This stu...Background:Lotus seedpod(Receptaculum Nelumbinis)is the abundant by-products produced during lotus seed processing,and the sources are usually considered to be wastes and are abandoned outdoors or incinerated.This study aims at predicting its bioactive compounds and cancer-related molecular targets against six cancers,including lung cancer,gastric cancer,liver cancer,breast cancer,ovarian cancer and cervical cancer.Methods:Network pharmacology and molecular docking methods were performed.Results:Network pharmacology results indicated that 14 core compounds(liensinine,tetrandrine,lysicamine,tricin,sanleng acid,cireneol G,ricinoleic acid,linolenic acid,5,7-dihydroxycoumarin,apigenin,luteolin,morin,quercetin and isorhamnetin)and 10 core targets(AKT1,ESR1,HSP90AA1,JUN,MAPK1,MAPK3,PIK3CA,PIK3R1,SRC and STAT3)were screened for lotus seedpod against the six cancers.Molecular docking analysis suggested that the binding abilities between the core compounds and the core targets were mostly strong.GO analysis revealed that the intersected targets between the bioactive compounds of lotus seedpod and the six cancers were significantly related to biological processes,cell compositions and molecular functions.KEGG analysis showed that PI3K-Akt,TNF,Ras,MAPK,HIF-1 and C-type lectin receptor signaling pathways were notably involved in the anti-cancer activities of lotus seedpod against the six cancers.Conclusions:14 core compounds and 10 core targets were screened for lotus seedpod against lung cancer,gastric cancer,liver cancer,breast cancer,ovarian cancer and cervical cancer.This study supports the application of lotus seedpod in treating cancers,and promotes the recycling and the high-value utilization.展开更多
Lumbar disc herniation(LDH)is a common orthopedic disease in clinical practice,with main symptoms of varying degrees of pain and functional impairment,seriously affecting the quality of work and life of patients,and a...Lumbar disc herniation(LDH)is a common orthopedic disease in clinical practice,with main symptoms of varying degrees of pain and functional impairment,seriously affecting the quality of work and life of patients,and also causing a certain degree of economic burden to the patient's family and society.At present,there are various conservative treatment methods for LDH in clinical practice.Conservative treatment has the characteristics of small trauma and high safety,which can achieve symptom relief and cure for most patients in clinical practice.This article aims to provide a scientific reference for the selection of treatment plans for LDH patients by reviewing relevant literature on conservative treatment of LDH that has been publicly reported both domestically and internationally in recent years.展开更多
Objective:To investigate the clinical effects of parental participation in nursing under the Interaction Model of Client Health Behavior(IMCHB)model in neonatal hypoxic-ischemic encephalopathy(HIE).Methods:The First A...Objective:To investigate the clinical effects of parental participation in nursing under the Interaction Model of Client Health Behavior(IMCHB)model in neonatal hypoxic-ischemic encephalopathy(HIE).Methods:The First Affiliated Hospital of Gannan Medical University included 46 newborns with HIE admitted from October 2021 to October 2023 into the study population.They were divided into a control group and an observation group according to the random number table method,with the control group adopting routine nursing,and the observation group implementing parental participation in nursing under the IMCHB model.The indicators of physical,intellectual,and psychomotor development of the two groups were compared before and after nursing.Results:The physical,intellectual,and psychomotor development of the observation group was higher than that of the control group after 3 months of nursing,and the difference was statistically significant(P<0.05).Conclusion:The implementation of the IMCHB model of parental participation in the clinical care of HIE neonates can further promote their physical,intellectual,and psychomotor development.展开更多
Art education is an important part of the comprehensive implementation of quality-oriented education, and it is an important method for medical students to recognize perceptual world, to enrich their thoughts and feel...Art education is an important part of the comprehensive implementation of quality-oriented education, and it is an important method for medical students to recognize perceptual world, to enrich their thoughts and feelings, and to regulate their physical and mental health, so it is very important for the growth of medical students under the background of education reform. Based on the analysis of the existing problems of art education in medical universities, this paper points out the importance of art education for medical students in medical universities, and tries to make some countermeasures and suggestions to strengthen the art education for medical students.展开更多
AIM:To explore changes in the optic disc and peripapillary atrophy(PPA)in school-age children with ametropia using color fundus photography combined with artificial intelligence(AI)technology.METHODS:Based on the retr...AIM:To explore changes in the optic disc and peripapillary atrophy(PPA)in school-age children with ametropia using color fundus photography combined with artificial intelligence(AI)technology.METHODS:Based on the retrospective case-controlled study,226 eyes of 113 children aged aged 6–12y were enrolled from October 2021 to May 2022.According to the results of spherical equivalent(SE),the children were divided into four groups:low myopia group(66 eyes),moderate myopia group(60 eyes),high myopia group(50 eyes)and emmetropia control group(50 eyes).All subjects underwent un-aided visual acuity,dilated pupil optometry,best-corrected visual acuity(BCVA),intraocular pressure,ocular axis measurement and color fundus photography.RESULTS:The width of PPA,horizontal diameter ratio of PPA to the optic disc and area ratio of PPA to the optic disc were significantly different among the four groups(P<0.05).The width of the nasal and temporal neuroretinal rim,the roundness of the optic disc,the height of PPA,the vertical diameter ratio of PPA to the optic disc,and the average density of PPA in the high myopia group were significantly different compared with the other three groups(P<0.05).There were strong negative correlations between SE and area ratio of PPA to the optic disc(r=-0.812,P<0.001)and strong positive correlation between axial length(AL)and area ratio of PPA to the optic disc(r=0.736,P<0.001).CONCLUSION:In school-age children with high myopia,the nasal and temporal neuroretinal rims are narrowed and even lost,which have high sensitivity.The area ratio of the PPA to the optic disc could be used as an early predictor of myopia progression,which is of great significance for the development prevention and management of myopia.展开更多
Polyphenol-rich foods have been shown to be good for cancer prevention as powerful antioxidants. In this study, the mechanisms of wild pink bayberry free phenolic extract(WPBFE)inhibiting the proliferation and inducin...Polyphenol-rich foods have been shown to be good for cancer prevention as powerful antioxidants. In this study, the mechanisms of wild pink bayberry free phenolic extract(WPBFE)inhibiting the proliferation and inducing apoptotic of MDA-MB-231 breast cancer cells was examined. The main phenolic acids and flavonols in WPBFE were gallic acid((18.83 ± 0.44)μg/g FW)and myricetin((1.52 ± 0.05)μg/g FW), respectively. The maximum inhibition rate of WPBFE at non-cytotoxicity dose(below 80 mg/mL)was 81%. Western blotting analysis showed that WPBFE could cause the arrest of cell cycle in G0/G1 phase by down-regulating expression levels of PCNA, CDK4, cyclin D1 and up-regulating the expression level of p21. Meanwhile, WPBFE induced apoptosis through initiating the mitochondrial death pathway by up-regulating cleaved caspase-3 and enhancing the ratio of Bax/Bcl-2, with the maximum expression levels of 1.29 and 2.03 folds that of control group, respectively. Further study of the upstream protein, we found that WPBFE down-regulated TRAF2, while upregulated p-ASK1, p-p38 and p-p53. Furthermore, WPBFE could down-regulate the expression of p-PI3K and p-Akt. These observations indicated that WPBFE might play an anticancer role through regulating the p38 MAPK together with PI3K/Akt pathway.展开更多
Background: Sepsis involves life-threatening organ dysfunction and is caused by a dysregulated host response to infection. No specific therapies against sepsis have been reported. Celastrol(Cel) is a natural anti-infl...Background: Sepsis involves life-threatening organ dysfunction and is caused by a dysregulated host response to infection. No specific therapies against sepsis have been reported. Celastrol(Cel) is a natural anti-inflammatory compound that shows potential against systemic inflammatory diseases. This study aimed to investigate the pharmacological activity and molecular mechanism of Cel in models of endotoxemia and sepsis.Methods: We evaluated the anti-inflammatory efficacy of Cel against endotoxemia and sepsis in mice and macrophage cultures treated with lipopolysaccharide(LPS). We screened for potential protein targets of Cel using activity-based protein profiling(ABPP). Potential targets were validated using biophysical methods such as cellular thermal shift assays(CETSA) and surface plasmon resonance(SPR). Residues involved in Cel binding to target proteins were identified through point mutagenesis, and the functional effects of such binding were explored through gene knockdown.Results: Cel protected mice from lethal endotoxemia and improved their survival with sepsis, and it significantly decreased the levels of pro-inflammatory cytokines in mice and macrophages treated with LPS(P <0.05). Cel bound to Cys424 of pyruvate kinase M2(PKM2), inhibiting the enzyme and thereby suppressing aerobic glycolysis(Warburg effect). Cel also bound to Cys106 in high mobility group box 1(HMGB1) protein, reducing the secretion of inflammatory cytokine interleukin(IL)-1β. Cel bound to the Cys residues in lactate dehydrogenase A(LDHA).Conclusions: Cel inhibits inflammation and the Warburg effect in sepsis via targeting PKM2 and HMGB1 protein.展开更多
BACKGROUND We report on a large family of Chinese Han individuals with hidrotic ectodermal dysplasia(HED)with a variation in GJB6(c.31G>A).The patients in the family had a triad of clinical manifestations of varyin...BACKGROUND We report on a large family of Chinese Han individuals with hidrotic ectodermal dysplasia(HED)with a variation in GJB6(c.31G>A).The patients in the family had a triad of clinical manifestations of varying degrees.Although the same variation locus have been reported,the clinical manifestations of this family were difficult to distinguish from those of congenital thick nail disorder,palmoplantar keratosis,and congenital hypotrichosis.CASE SUMMARY This investigation involved a large Chinese family of 46 members across five generations and included 12 patients with HED.The proband(IV4)was a male patient with normal sweat gland function and dental development,no skeletal dysplasia,no cognitive disability,and no hearing impairments.His parents were not consanguineously married.Physical examination of the proband revealed thinning hair and thickened grayish-yellow nails and toenails with some longit-udinal ridges,in addition to mild bilateral palmoplantar hyperkeratosis.GJB6,GJB2,and GJA1 have been reported to be the causative genes of HED;therefore,we subjected the patient’s samples to Sanger sequencing of these three genes.In this family,the variation locus was at GJB6(c.31G>A,p.Gly11Arg).Overex-pression vectors of wild-type GJB6 and its variants were established and transfected into HaCaT cell models,and the related mRNA and protein expression changes were determined using real-time reverse transcriptase-polymerase chain reaction and Western blot,respectively.CONCLUSION We report another HED phenotype associated with GJB6 variations,which can help clinicians to diagnose HED despite its varying presentations.展开更多
Background:The purpose of our study was to study the composition and content of the feline plasma metabolome revealing the critical metabolites and metabolic pathways associated with age during growth and development....Background:The purpose of our study was to study the composition and content of the feline plasma metabolome revealing the critical metabolites and metabolic pathways associated with age during growth and development.Methods:Blood samples were collected from juvenile and adult groups for blood routine tests and serum biochemistry tests.Non-targeted metabolomics analyses of plasma were also performed to investigate changes in metabolites and metabolic pathways.Results:In this study,we found that the red blood cell counts,liver function indexes(albumin and gamma-glutamyl transpeptidase),and the concentration of triglyceride and glucose changed significant with growth and development.The metabolomics results revealed that 1427 metabolites were identified in the plasma of young and adult cats.Most of these metabolites belong to major classes of lipids and lipid-like molecules.The most obvious age-related metabolites include reduced levels of chenodeoxycholate,taurocholate,cholate,and taurochenodeoxycholate but increased levels of L-cysteine and taurocyamine in the adult cat's serum.These metabolites are mainly involved in the primary bile acid biosynthesis pathway,the bile secretion pathway,and the taurine and hypotaurine metabolism pathway.Conclusion:This study revealed many age-related metabolite alterations in the feline plasma.These age-varying metabolites,especially in the bile acid biosynthesis and secretion metabolism pathways,indicate that the regulation of these pathways is involved in the growth and development of cats.This study promotes our understanding of the mechanism of feline growth and provides new insights into nutrition and medicine for cats of different ages.展开更多
Heart failure(HF)is a widespread clinical syndrome worldwide that imposes an enormous burden on healthcare systems.[1,2]Loop diuretics are one of the cornerstones for treating HF,considering that extracellular fluid v...Heart failure(HF)is a widespread clinical syndrome worldwide that imposes an enormous burden on healthcare systems.[1,2]Loop diuretics are one of the cornerstones for treating HF,considering that extracellular fluid volume expansion plays a crucial role in the pathogenesis of congestive HF.[3]According to recent European registries,diuretics are prescribed in more than 80%of hospitalized and discharged patients with HF.展开更多
The reported cases of food allergies are steadily increasing.With the invention of more novel foods,new and unfamiliar allergens are being introduced into our diets,which raises concerns about the potential risk of no...The reported cases of food allergies are steadily increasing.With the invention of more novel foods,new and unfamiliar allergens are being introduced into our diets,which raises concerns about the potential risk of novel food allergies.The purpose of this review is to assess the allergenic risks associated with novel food components,strategies for assessing risk in relation to novel food allergens,and current regulations for managing food allergens in novel food products.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81971309 (to CY),32170980 (to CY),82260272 (to DL)the Natural Science Foundation of Jiangxi Province,No.20192BAB205078 (to DL)+1 种基金Guangdong Basic and Applied Basic Research Foundation,No.2022B1515020012 (to CY)Shenzhen Fundamental Research Program,Nos.JCYJ20210324123212035 (to CY),RCYX202007141 14644167 (to CY),ZDSYS20220606100801003 (to CY)。
文摘Alzheimer's disease(AD) is a progressive and degenerative neurological disease characterized by the deterioration of cognitive functions. While a definitive cure and optimal medication to impede disease progression are currently unavailable, a plethora of studies have highlighted the potential advantages of exercise rehabilitation for managing this condition. Those studies show that exercise rehabilitation can enhance cognitive function and improve the quality of life for individuals affected by AD. Therefore, exercise rehabilitation has been regarded as one of the most important strategies for managing patients with AD. Herein, we provide a comprehensive analysis of the currently available findings on exercise rehabilitation in patients with AD, with a focus on the exercise types which have shown efficacy when implemented alone or combined with other treatment methods, as well as the potential mechanisms underlying these positive effects. Specifically, we explain how exercise may improve the brain microenvironment and neuronal plasticity. In conclusion, exercise is a cost-effective intervention to enhance cognitive performance and improve quality of life in patients with mild to moderate cognitive dysfunction. Therefore, it can potentially become both a physical activity and a tailored intervention. This review may aid the development of more effective and individualized treatment strategies to address the challenges imposed by this debilitating disease, especially in low-and middle-income countries.
基金the National Natural Science Foundation of China(Grant No.:82360542)Jiangxi Provincial Natural Science Foundation,China(Grant Nos.:20224BAB214030 and 20224BAB216072)+2 种基金Doctoral Startup Fund of Gannan Medical University,China(Grant Nos.:QD202136 and QD202132)Science and Technology Planning Projects of Fuzhou,China(Grant No.:2021FZR0101)the Natural Science Foundation of Fujian Province,China(Grant No.:2022YZ0104).
文摘Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced functionality.Mutation or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenesis can result in different types of ribosomopathies in clinic,collectively known as ribosomopathy genes.Emerging data suggest that ribosomopathy patients exhibit a significantly heightened susceptibility to cancer.Abnormal ribosome biogenesis and dysregulation of some ribosomopathy genes have also been found to be intimately associated with cancer development.The correlation between ribosome biogenesis or ribosomopathy and the development of malignancies has been well established.This work aims to review the recent advances in the research of ribosomopathy genes among human cancers and meanwhile,to excavate the potential role of these genes,which have not or rarely been reported in cancer,in the disease development across cancers.We plan to establish a theoretical framework between the ribosomopathy gene and cancer development,to further facilitate the potential of these genes as diagnostic biomarker as well as pharmaceutical targets for cancer treatment.
基金Supported by the National Natural Science Foundation of China,No.32060232Jiangxi Provincial Natural Science Foundation,No.20212BAB206075.
文摘BACKGROUND The efficacy of mesenchymal stem cells(MSCs)in treating liver fibrosis has been demonstrated in several clinical studies.However,their low survival and liver implantation rates remain problematic.In recent years,a large number of studies in animal models of liver fibrosis have shown that MSCs combined with drugs can improve the efficacy of MSCs in the treatment of liver fibrosis alone and inhibit its progression to end-stage liver disease.This has inspired new ways of thinking about treating liver fibrosis.AIM To investigate the effectiveness and mechanisms of MSCs combined with drugs in treating liver fibrosis.METHODS Data sources included four electronic databases and were constructed until January 2024.The subjects,interventions,comparators,outcomes,and study design principle were used to screen the literature,and the quality of the literature was evaluated to assess the risk of bias.Relevant randomised controlled trials were selected,and the final 13 studies were included in the final study.RESULTS A total of 13 studies were included after screening.Pooled analysis showed that MSCs combined with drug therapy significantly improved liver function,promoted the repair of damaged liver tissues,reduced the level of liver fibrosis-related indexes,and effectively ameliorated hepatic fibrosis by modulating the hepatic inflammatory microenvironment,promoting the homing of MSCs,and regulating the relevant signaling pathways,and the treatment efficacy was superior to MSCs alone.However,the combined treatment statistics showed no amelioration in serum albumin levels(standardized mean difference=0.77,95%confidence interval:-0.13 to 1.68,P=0.09).CONCLUSION In conclusion,MSCs combined with drugs for treating liver fibrosis effectively make up for the shortcomings of MSCs in their therapeutic effects.However,due to the different drugs,the treatment mechanism and effect also differ.Therefore,more randomized controlled trials are needed to compare the therapeutic efficacy of different drugs in combination with MSCs,aiming to select the“best companion”of MSCs in treating hepatic fibrosis.
基金the Ethic Committee of Second Affiliated Hospital of Gannan Medical University。
文摘BACKGROUND Psychological intervention nursing(PIN)has been considered to have a curative effect on cesarean section(CS)post-operative recovery.However,the therapeutic mechanisms remain obscure.AIM To explore the effects of PIN combined with acupressure massage on CS postoperative recovery.METHODS A retrospective study was conducted on 150 pregnant women admitted to an obstetrics department between January 2020 and January 2023.The control group(CG)received acupressure therapy(n=73),and the intervention group(IG)received acupressure therapy and PIN therapy(n=77).Postoperative recovery time was assessed by anal-exhausting,defecation,bed activity,breastfeeding,and hospital stay times.Adverse effects,including infection,bleeding,limb numbness,intrauterine hematoma,urinary retention,and venous thromboembolism,were recorded.the pain visual analogue scale(VAS)was used to evaluate the degree of pain.Anxiety and depression status were qualitatively assessed using the selfrating anxiety scale(SAS),self-rating depression scale(SDS),and Edinburgh postpartum depression scale(EPDS).The Pittsburgh sleep quality index(PSQI)was used to compare sleep quality between the groups.RESULTS The baseline data and SAS,SDS,EPDS,and PSQI scores did not significantly differ before CS(P>0.05)and neither did complication rates between the two groups after CS(P>0.05).However,anal-exhausting,defecation,waking up,breastfeeding,and hospitalization times were significantly shorter for participants in the IG than those for participants in the CG(P<0.05).The VAS,SAS,SDS,EPDS,and PSQI scores of the IG were significantly lower than those of the CG(P<0.05).CONCLUSION PIN,combined with acupressure massage,effectively promotes maternal recovery,reduces post-CS pain,and improves post-operative negative emotions and sleeping quality.
文摘Weak redox ability and severe charge recombination pose significant obstacles to the advancement of CO_(2) photoreduction.To tackle this challenge and enhance the CO_(2) photoconversion efficiency,fabricating well-matched S-scheme heterostructure and establishing a robust built-in electric field emerge as pivotal strategies.In pursuit of this goal,a core-shell structured CuInS_(2)@CoS_(2)S-scheme heterojunction was meticulously engineered through a two-step molten salt method.This approach over the CuInS_(2)-based composites produced an internal electric field owing to the disparity be-tween the Fermi levels of CoS_(2) and CuInS_(2) at their interface.Consequently,the electric field facili-tated the directed migration of charges and the proficient separation of photoinduced carriers.The resulting CuInS_(2)@CoS_(2) heterostructure exhibited remarkable CO_(2) photoreduction performance,which was 21.7 and 26.5 times that of pure CuInS_(2) and CoS_(2),respectively.The S-scheme heterojunc-tion photogenerated charge transfer mechanism was validated through a series of rigorous anal-yses,including in situ irradiation X-ray photoelectron spectroscopy,work function calculations,and differential charge density examinations.Furthermore,in situ infrared spectroscopy and density functional theory calculations corroborated the fact that the CuInS_(2)@CoS_(2) heterojunction substan-tially lowered the formation energy of *COOH and *CO.This study demonstrates the application potential of S-scheme heterojunctions fabricated via the molten salt method in the realm of ad-dressing carbon-related environmental issues.
文摘Non-alcoholic fatty liver disease(NAFLD)poses a significant health challenge in modern societies due to shifts in lifestyle and dietary habits.Its complexity stems from genetic predisposition,environmental influences,and metabolic factors.Epigenetic processes govern various cellular functions such as transcription,chromatin structure,and cell division.In NAFLD,these epigenetic tendencies,especially the process of histone methylation,are intricately intertwined with fat accumulation in the liver.Histone methylation is regulated by different enzymes like methyltransferases and demethylases and influences the expression of genes related to adipogenesis.While early-stage NAFLD is reversible,its progression to severe stages becomes almost irreversible.Therefore,early detection and intervention in NAFLD are crucial,and understanding the precise role of histone methylation in the early stages of NAFLD could be vital in halting or potentially reversing the progression of this disease.
基金Supported by National Nature Science Foundation of China,No.82060450,No.82360517,No.81460374,and No.31460304Nature Science Foundation of Jiangxi Province of China,No.20232BAB206086,No.20192BAB205072,No.20203BBGL73206,No.2017BCB23086,No.2017BAB205062,and No.20181BAB205050.
文摘BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.METHODS This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April 2007.Patients were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)staining.The expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients.Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015.The relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient.The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival analysis.RESULTS TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous tissue.The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multivariate analysis indicated that high expression of pSMAD3L(S204)and VEGFR-1 were independent risk factors for prognosis in GC patients.VEGFR-1 protein expression was correlated with TGF-β1(r=0.220,P=0.029),pSMAD3C(S423/425)(r=0.302,P=0.002),and pSMAD3L(S204)(r=0.201,P=0.047),respectively.Simultaneous overexpression of pSMAD3L(S204)and VEGFR-1 was associated with poor OS in gastric cancer patients.CONCLUSION Co-upregulation of pSMAD3L(S204)and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis,and pSMAD3L(204)may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.
文摘BACKGROUND Eccrine porocarcinoma(EPC)is a rare skin tumor that mainly affects the elderly population.Tumors often present with slow growth and a good prognosis.EPCs are usually distinguished from other skin tumors using histopathology and immunohistochemistry.However,surgical management alone may be inadequate if the tumor has metastasized.However,currently,surgical resection is the most commonly used treatment modality.CASE SUMMARY A seventy-four-year-old woman presented with a slow-growing nodule in her left temporal area,with no obvious itching or pain,for more than four months.Histopathological examination showed small columnar and short spindle-shaped cells;thus,basal cell carcinoma was suspected.However,immunohistochemical analysis revealed the expression of cytokeratin 5/6,p63 protein,p16 protein,and Ki-67 antigen(40%),and EPC was taken into consideration.The skin biopsy was repeated,and hematoxylin and eosin staining revealed ductal differentiation in some cells.Finally,the patient was diagnosed with EPC,and Mohs micrographic surgery was performed.We adapted follow-up visits in a year and not found any recurrence of nodules.CONCLUSION This case report emphasizes the diagnosis and differentiation of EPC.
基金the National Key Research and Development Program of China(2020YFA0908000,2022YFC2303600)the National Natural Science Foundation of China(81903866,82274182)and the Central Public Welfare Research Institutes(ZZ13-YQ-105,ZZ15-YQ-065,ZZ14-YQ-058).
文摘Objective:Celastrol is a pentacyclic triterpenoid extracted from the traditional Chinese medicinal herb,Tripterygium wilfordii.This study aims to provide a scientific basis for the rational development and use of celastrol in breast cancer.Method:A quantitative chemical biology approach was used to investigate the protein targets and molecular mechanisms of celastrol in breast cancer cells.Results:Low-concentration celastrol exerted an anti-tumor effect by directly binding to hydroxysteroid dehydrogenase-like 2(HSDL2)and inhibiting its expression.Moreover,the expression of the pro-apoptotic protein,Bcl-2-associated X(BaX),increased,the level of the anti-apoptotic protein,B-cell lymphoma-2(Bcl-2),decreased,and the rate of apoptosis increased.After the transfection of cells with si-HSDL2,the apoptosis rate was similar to that observed after the administration of celastrol.However,apoptosis was reversed by the overexpression of HSDL2.Furthermore,our mass spectrometry(MS)data indicated a relationship between HSDL2 and the mitogen-activated protein kinase(MAPK)signaling pathway.We also found that the expression of HSDL2 was directly related to the degree of extracellular signal-regulated kinase(ERK)phosphorylation.Conclusion:Celastrol may promote apoptosis by suppressing the HSDL2/MAPK/ERK signaling pathway.
基金This work was funded by the Science and Technology Research Project of Jiangxi Provincial Education Department[GJJ190805&GJJ211507]Jiangxi Provincial Natural Science Foundation[20232BAB215062&20202BABL216081]+1 种基金University-Level Scientific Research Projects of Gannan Medical University[QD201913&QD202128]and the Jiangxi Provincial College Students Innovation and Entrepreneurship Training Programs[S202210413028&S202310413031].
文摘Background:Lotus seedpod(Receptaculum Nelumbinis)is the abundant by-products produced during lotus seed processing,and the sources are usually considered to be wastes and are abandoned outdoors or incinerated.This study aims at predicting its bioactive compounds and cancer-related molecular targets against six cancers,including lung cancer,gastric cancer,liver cancer,breast cancer,ovarian cancer and cervical cancer.Methods:Network pharmacology and molecular docking methods were performed.Results:Network pharmacology results indicated that 14 core compounds(liensinine,tetrandrine,lysicamine,tricin,sanleng acid,cireneol G,ricinoleic acid,linolenic acid,5,7-dihydroxycoumarin,apigenin,luteolin,morin,quercetin and isorhamnetin)and 10 core targets(AKT1,ESR1,HSP90AA1,JUN,MAPK1,MAPK3,PIK3CA,PIK3R1,SRC and STAT3)were screened for lotus seedpod against the six cancers.Molecular docking analysis suggested that the binding abilities between the core compounds and the core targets were mostly strong.GO analysis revealed that the intersected targets between the bioactive compounds of lotus seedpod and the six cancers were significantly related to biological processes,cell compositions and molecular functions.KEGG analysis showed that PI3K-Akt,TNF,Ras,MAPK,HIF-1 and C-type lectin receptor signaling pathways were notably involved in the anti-cancer activities of lotus seedpod against the six cancers.Conclusions:14 core compounds and 10 core targets were screened for lotus seedpod against lung cancer,gastric cancer,liver cancer,breast cancer,ovarian cancer and cervical cancer.This study supports the application of lotus seedpod in treating cancers,and promotes the recycling and the high-value utilization.
文摘Lumbar disc herniation(LDH)is a common orthopedic disease in clinical practice,with main symptoms of varying degrees of pain and functional impairment,seriously affecting the quality of work and life of patients,and also causing a certain degree of economic burden to the patient's family and society.At present,there are various conservative treatment methods for LDH in clinical practice.Conservative treatment has the characteristics of small trauma and high safety,which can achieve symptom relief and cure for most patients in clinical practice.This article aims to provide a scientific reference for the selection of treatment plans for LDH patients by reviewing relevant literature on conservative treatment of LDH that has been publicly reported both domestically and internationally in recent years.
文摘Objective:To investigate the clinical effects of parental participation in nursing under the Interaction Model of Client Health Behavior(IMCHB)model in neonatal hypoxic-ischemic encephalopathy(HIE).Methods:The First Affiliated Hospital of Gannan Medical University included 46 newborns with HIE admitted from October 2021 to October 2023 into the study population.They were divided into a control group and an observation group according to the random number table method,with the control group adopting routine nursing,and the observation group implementing parental participation in nursing under the IMCHB model.The indicators of physical,intellectual,and psychomotor development of the two groups were compared before and after nursing.Results:The physical,intellectual,and psychomotor development of the observation group was higher than that of the control group after 3 months of nursing,and the difference was statistically significant(P<0.05).Conclusion:The implementation of the IMCHB model of parental participation in the clinical care of HIE neonates can further promote their physical,intellectual,and psychomotor development.
文摘Art education is an important part of the comprehensive implementation of quality-oriented education, and it is an important method for medical students to recognize perceptual world, to enrich their thoughts and feelings, and to regulate their physical and mental health, so it is very important for the growth of medical students under the background of education reform. Based on the analysis of the existing problems of art education in medical universities, this paper points out the importance of art education for medical students in medical universities, and tries to make some countermeasures and suggestions to strengthen the art education for medical students.
文摘AIM:To explore changes in the optic disc and peripapillary atrophy(PPA)in school-age children with ametropia using color fundus photography combined with artificial intelligence(AI)technology.METHODS:Based on the retrospective case-controlled study,226 eyes of 113 children aged aged 6–12y were enrolled from October 2021 to May 2022.According to the results of spherical equivalent(SE),the children were divided into four groups:low myopia group(66 eyes),moderate myopia group(60 eyes),high myopia group(50 eyes)and emmetropia control group(50 eyes).All subjects underwent un-aided visual acuity,dilated pupil optometry,best-corrected visual acuity(BCVA),intraocular pressure,ocular axis measurement and color fundus photography.RESULTS:The width of PPA,horizontal diameter ratio of PPA to the optic disc and area ratio of PPA to the optic disc were significantly different among the four groups(P<0.05).The width of the nasal and temporal neuroretinal rim,the roundness of the optic disc,the height of PPA,the vertical diameter ratio of PPA to the optic disc,and the average density of PPA in the high myopia group were significantly different compared with the other three groups(P<0.05).There were strong negative correlations between SE and area ratio of PPA to the optic disc(r=-0.812,P<0.001)and strong positive correlation between axial length(AL)and area ratio of PPA to the optic disc(r=0.736,P<0.001).CONCLUSION:In school-age children with high myopia,the nasal and temporal neuroretinal rims are narrowed and even lost,which have high sensitivity.The area ratio of the PPA to the optic disc could be used as an early predictor of myopia progression,which is of great significance for the development prevention and management of myopia.
基金the support from the Guangdong Basic and Applied Basic Research Foundation (2020A1515011376)the National Natural Science Foundation of China (31601397)+2 种基金the Innovative Leading Talents Project of Guangzhou Development ZoneGuangzhou Innovation Leading Talent Projectthe 111 Project (B17018)。
文摘Polyphenol-rich foods have been shown to be good for cancer prevention as powerful antioxidants. In this study, the mechanisms of wild pink bayberry free phenolic extract(WPBFE)inhibiting the proliferation and inducing apoptotic of MDA-MB-231 breast cancer cells was examined. The main phenolic acids and flavonols in WPBFE were gallic acid((18.83 ± 0.44)μg/g FW)and myricetin((1.52 ± 0.05)μg/g FW), respectively. The maximum inhibition rate of WPBFE at non-cytotoxicity dose(below 80 mg/mL)was 81%. Western blotting analysis showed that WPBFE could cause the arrest of cell cycle in G0/G1 phase by down-regulating expression levels of PCNA, CDK4, cyclin D1 and up-regulating the expression level of p21. Meanwhile, WPBFE induced apoptosis through initiating the mitochondrial death pathway by up-regulating cleaved caspase-3 and enhancing the ratio of Bax/Bcl-2, with the maximum expression levels of 1.29 and 2.03 folds that of control group, respectively. Further study of the upstream protein, we found that WPBFE down-regulated TRAF2, while upregulated p-ASK1, p-p38 and p-p53. Furthermore, WPBFE could down-regulate the expression of p-PI3K and p-Akt. These observations indicated that WPBFE might play an anticancer role through regulating the p38 MAPK together with PI3K/Akt pathway.
基金suppor ted by the National Key Research and Development Program of China(2020YFA0908000)the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(ZYYCXTD-C-202002)+1 种基金the National Natural Science Foundation of China(82074098,81841001)the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZXKT18003)。
文摘Background: Sepsis involves life-threatening organ dysfunction and is caused by a dysregulated host response to infection. No specific therapies against sepsis have been reported. Celastrol(Cel) is a natural anti-inflammatory compound that shows potential against systemic inflammatory diseases. This study aimed to investigate the pharmacological activity and molecular mechanism of Cel in models of endotoxemia and sepsis.Methods: We evaluated the anti-inflammatory efficacy of Cel against endotoxemia and sepsis in mice and macrophage cultures treated with lipopolysaccharide(LPS). We screened for potential protein targets of Cel using activity-based protein profiling(ABPP). Potential targets were validated using biophysical methods such as cellular thermal shift assays(CETSA) and surface plasmon resonance(SPR). Residues involved in Cel binding to target proteins were identified through point mutagenesis, and the functional effects of such binding were explored through gene knockdown.Results: Cel protected mice from lethal endotoxemia and improved their survival with sepsis, and it significantly decreased the levels of pro-inflammatory cytokines in mice and macrophages treated with LPS(P <0.05). Cel bound to Cys424 of pyruvate kinase M2(PKM2), inhibiting the enzyme and thereby suppressing aerobic glycolysis(Warburg effect). Cel also bound to Cys106 in high mobility group box 1(HMGB1) protein, reducing the secretion of inflammatory cytokine interleukin(IL)-1β. Cel bound to the Cys residues in lactate dehydrogenase A(LDHA).Conclusions: Cel inhibits inflammation and the Warburg effect in sepsis via targeting PKM2 and HMGB1 protein.
文摘BACKGROUND We report on a large family of Chinese Han individuals with hidrotic ectodermal dysplasia(HED)with a variation in GJB6(c.31G>A).The patients in the family had a triad of clinical manifestations of varying degrees.Although the same variation locus have been reported,the clinical manifestations of this family were difficult to distinguish from those of congenital thick nail disorder,palmoplantar keratosis,and congenital hypotrichosis.CASE SUMMARY This investigation involved a large Chinese family of 46 members across five generations and included 12 patients with HED.The proband(IV4)was a male patient with normal sweat gland function and dental development,no skeletal dysplasia,no cognitive disability,and no hearing impairments.His parents were not consanguineously married.Physical examination of the proband revealed thinning hair and thickened grayish-yellow nails and toenails with some longit-udinal ridges,in addition to mild bilateral palmoplantar hyperkeratosis.GJB6,GJB2,and GJA1 have been reported to be the causative genes of HED;therefore,we subjected the patient’s samples to Sanger sequencing of these three genes.In this family,the variation locus was at GJB6(c.31G>A,p.Gly11Arg).Overex-pression vectors of wild-type GJB6 and its variants were established and transfected into HaCaT cell models,and the related mRNA and protein expression changes were determined using real-time reverse transcriptase-polymerase chain reaction and Western blot,respectively.CONCLUSION We report another HED phenotype associated with GJB6 variations,which can help clinicians to diagnose HED despite its varying presentations.
基金supported by grants from the National Science Foundation of China,grant numbers 82260121 and 82200327Zhanggong Science and Technology Plan Project+2 种基金the Hubei Province Innovation Platform Construction Projectgrant number 20204201117303072238Hubei Provincial Engineering Research Center of Model Animal
文摘Background:The purpose of our study was to study the composition and content of the feline plasma metabolome revealing the critical metabolites and metabolic pathways associated with age during growth and development.Methods:Blood samples were collected from juvenile and adult groups for blood routine tests and serum biochemistry tests.Non-targeted metabolomics analyses of plasma were also performed to investigate changes in metabolites and metabolic pathways.Results:In this study,we found that the red blood cell counts,liver function indexes(albumin and gamma-glutamyl transpeptidase),and the concentration of triglyceride and glucose changed significant with growth and development.The metabolomics results revealed that 1427 metabolites were identified in the plasma of young and adult cats.Most of these metabolites belong to major classes of lipids and lipid-like molecules.The most obvious age-related metabolites include reduced levels of chenodeoxycholate,taurocholate,cholate,and taurochenodeoxycholate but increased levels of L-cysteine and taurocyamine in the adult cat's serum.These metabolites are mainly involved in the primary bile acid biosynthesis pathway,the bile secretion pathway,and the taurine and hypotaurine metabolism pathway.Conclusion:This study revealed many age-related metabolite alterations in the feline plasma.These age-varying metabolites,especially in the bile acid biosynthesis and secretion metabolism pathways,indicate that the regulation of these pathways is involved in the growth and development of cats.This study promotes our understanding of the mechanism of feline growth and provides new insights into nutrition and medicine for cats of different ages.
基金supported by the Health Commission of Jiangxi Provincial of China (No. 202311965)
文摘Heart failure(HF)is a widespread clinical syndrome worldwide that imposes an enormous burden on healthcare systems.[1,2]Loop diuretics are one of the cornerstones for treating HF,considering that extracellular fluid volume expansion plays a crucial role in the pathogenesis of congestive HF.[3]According to recent European registries,diuretics are prescribed in more than 80%of hospitalized and discharged patients with HF.
基金Central Government Guide Local Special Fund Project for Scientific and Technological Development of Jiangxi Province(20221ZDD02001).
文摘The reported cases of food allergies are steadily increasing.With the invention of more novel foods,new and unfamiliar allergens are being introduced into our diets,which raises concerns about the potential risk of novel food allergies.The purpose of this review is to assess the allergenic risks associated with novel food components,strategies for assessing risk in relation to novel food allergens,and current regulations for managing food allergens in novel food products.