BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related mortality worldwide,primarily due to tumor heterogeneity and treatment resistance.The leucine-rich repeat-containing protein 19(LRRC19)has been lin...BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related mortality worldwide,primarily due to tumor heterogeneity and treatment resistance.The leucine-rich repeat-containing protein 19(LRRC19)has been linked to immune regulation and tumor suppression,yet its specific role in CRC remains poorly understood.AIM To investigate the tumor-suppressive role of LRRC19 in CRC,focusing on cell cycle,immune microenvironment,and chemotherapy response.METHODS Bioinformatics analyses of Gene Expression Omnibus and The Cancer Genome Atlas databases identified differentially expressed genes in CRC.LRRC19 exp-ression was validated in CRC tissues and cell lines by quantitative PCR,immuno-histochemistry,and Western blotting.Functional assays,including proliferation,soft agar colony formation,flow cytometry,and xenograft models,assessed biological effects.Mechanistic studies with dual-luciferase reporter assays,molecular docking,and drug sensitivity testing explored LRRC19’s interaction with the cyclin-dependent kinase 6(CDK6)/E2F1 axis and oxaliplatin(OXA)response.Single-cell sequencing and immune infiltration analyses assessed its impact on the immune microenvironment.RESULTS LRRC19 expression was significantly downregulated in CRC and associated with poor prognosis.Overexpression of LRRC19 inhibited CRC cell proliferation,induced G0/G1 phase arrest,and suppressed tumor growth in vivo.Mechanistically,LRRC19 suppressed CDK6 transcription by downregulating E2F1,leading to cell cycle arrest.Additionally,LRRC19 promoted immune cell infiltration,particularly B cells and CD4+T cells,while decreasing immunosuppressive cells.LRRC19 also sensitized CRC cells to OXA,enhancing chemotherapy efficacy.CONCLUSION LRRC19 suppresses CRC by targeting the CDK6/E2F1 axis,modulating the immune microenvironment,and enhancing chemotherapy sensitivity,making it a promising therapeutic target for precision medicine in CRC.展开更多
Postmenopausal women with Alzheimer’s disease exhibit dramatically reduced sensitivity to estrogen replacement therapy,which is though to be related to an estrogen receptor(ER)α/ERβratio imbalance arising from a si...Postmenopausal women with Alzheimer’s disease exhibit dramatically reduced sensitivity to estrogen replacement therapy,which is though to be related to an estrogen receptor(ER)α/ERβratio imbalance arising from a significantly decreased level of ERs of the brain.The aim of our study was to investigate whether valproic acid(VPA)can enhance the beneficial effects of estrogen on cognitive function through restoration of ERαand ERβexpression in the brain.We removed the ovaries of female APP/PS1 mice to simulate the low estrogen levels present in postmenopausal women and then administered VPA(30 mg/kg,intraperitoneal injection,once daily),17β-estradiol(E2)(2.4μg,intraperitoneal injection,once daily),liquiritigenin(LG)(50μg/kg,intragastric infusion,once daily),VPA+E2,or VPA+LG for 4 successive weeks.Compared with treatment with a single drug,treatment with VPA+E2 or VPA+LG significantly increased the level of glycogen synthase kinase 3β,increased the expression of estrogen receptorα,reduced the expression of small ubiquitin-like modifiers,and increased the level of estrogen receptorβ.This resulted in enhanced sensitivity to estrogen therapy,reduced amyloidβaggregation,reduced abnormal phosphorylation of the tau protein,reduced neuronal loss,increased dendritic spine and postsynaptic density,and significantly alleviated memory loss and learning impairment in Alzheimer’s disease.This study was approved by the Chongqing Medical University Animal Protection and Ethics Committee,China on March 6,2013.展开更多
BACKGROUND Posterior scleritis is a rare inflammatory ocular disease,characterized by severe and painful inflammation of the sclera.It is often misdiagnosed or underdiagnosed,due to its general and varying clinical pr...BACKGROUND Posterior scleritis is a rare inflammatory ocular disease,characterized by severe and painful inflammation of the sclera.It is often misdiagnosed or underdiagnosed,due to its general and varying clinical presentation profile,which primarily involves pain and visual impairment but which can include eyelid edema,choroidal folds,serous retinal detachment,disc edema,hard exudates in fovea and subretinal mass.We report here a case of posterior scleritis,with symptoms of eye pain and red eye,initially misdiagnosed as acute conjunctivitis.CASE SUMMARY A 56-year-old man presented to a local hospital with complaint of pain and redness in the right eye.The initial diagnosis was acute conjunctivitis and he was given antibiotic eyedrops.Upon week-long continuance of the symptoms despite treatment,he presented to our hospital.Initial examination revealed a shallow anterior chamber in the right eye and vision reduction to 0.6.Further testing by optical coherence tomography,ultrasound biomicroscopy,and fundus photography indicated diagnosis of posterior scleritis.The patient was given methylprednisolone(oral)on a tapered reduction schedule(starting with 70 mg/d).According to the peaks and troughs of symptoms,compound betamethasone injection was administered into the bulb,culminating in discontinuation of the oral corticosteroid.Subsequent optical coherence tomography showed the subretinal fluid near the optic disc to be completely absorbed after treatment.CONCLUSION Posterior scleritis should be among the differential diagnosis of eye pain and redness,and diagnosis requires further ophthalmic accessory examination,such as by optical coherence tomography.展开更多
In this paper,a new organic–inorganic hybrid compound[Co(L)_(2)]2[W_(6)O_(19)](1)(HL=2-acetylpyridine thiosemicarbazone)was prepared and characterized.The compound 1 exhibits remarkable antibacterial activity by dete...In this paper,a new organic–inorganic hybrid compound[Co(L)_(2)]2[W_(6)O_(19)](1)(HL=2-acetylpyridine thiosemicarbazone)was prepared and characterized.The compound 1 exhibits remarkable antibacterial activity by determination of minimum inhibitory concentration(MIC)against Staphylococcus aureus(S.aureus,0.06μg·mL^(−1))and Escherichia coli(E.coli,0.24μg·mL^(−1)),respectively.Furthermore,the potential mechanism of compound 1 was studied in detail.The potential causes of bacteria death were cell wall/membrane disruption,inhibition of intracellular respiratory chain dehydrogenases(RCD)activity,destruction of reactive oxygen species(ROS)and depletion of glutathione(GSH).展开更多
基金Supported by the Natural Science Foundation of Zhejiang Province,No.LY22H160005。
文摘BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related mortality worldwide,primarily due to tumor heterogeneity and treatment resistance.The leucine-rich repeat-containing protein 19(LRRC19)has been linked to immune regulation and tumor suppression,yet its specific role in CRC remains poorly understood.AIM To investigate the tumor-suppressive role of LRRC19 in CRC,focusing on cell cycle,immune microenvironment,and chemotherapy response.METHODS Bioinformatics analyses of Gene Expression Omnibus and The Cancer Genome Atlas databases identified differentially expressed genes in CRC.LRRC19 exp-ression was validated in CRC tissues and cell lines by quantitative PCR,immuno-histochemistry,and Western blotting.Functional assays,including proliferation,soft agar colony formation,flow cytometry,and xenograft models,assessed biological effects.Mechanistic studies with dual-luciferase reporter assays,molecular docking,and drug sensitivity testing explored LRRC19’s interaction with the cyclin-dependent kinase 6(CDK6)/E2F1 axis and oxaliplatin(OXA)response.Single-cell sequencing and immune infiltration analyses assessed its impact on the immune microenvironment.RESULTS LRRC19 expression was significantly downregulated in CRC and associated with poor prognosis.Overexpression of LRRC19 inhibited CRC cell proliferation,induced G0/G1 phase arrest,and suppressed tumor growth in vivo.Mechanistically,LRRC19 suppressed CDK6 transcription by downregulating E2F1,leading to cell cycle arrest.Additionally,LRRC19 promoted immune cell infiltration,particularly B cells and CD4+T cells,while decreasing immunosuppressive cells.LRRC19 also sensitized CRC cells to OXA,enhancing chemotherapy efficacy.CONCLUSION LRRC19 suppresses CRC by targeting the CDK6/E2F1 axis,modulating the immune microenvironment,and enhancing chemotherapy sensitivity,making it a promising therapeutic target for precision medicine in CRC.
基金This study was supported by the National Natural Science Foundation of China,Nos.81671257,81371221,31600825(all to GQH).
文摘Postmenopausal women with Alzheimer’s disease exhibit dramatically reduced sensitivity to estrogen replacement therapy,which is though to be related to an estrogen receptor(ER)α/ERβratio imbalance arising from a significantly decreased level of ERs of the brain.The aim of our study was to investigate whether valproic acid(VPA)can enhance the beneficial effects of estrogen on cognitive function through restoration of ERαand ERβexpression in the brain.We removed the ovaries of female APP/PS1 mice to simulate the low estrogen levels present in postmenopausal women and then administered VPA(30 mg/kg,intraperitoneal injection,once daily),17β-estradiol(E2)(2.4μg,intraperitoneal injection,once daily),liquiritigenin(LG)(50μg/kg,intragastric infusion,once daily),VPA+E2,or VPA+LG for 4 successive weeks.Compared with treatment with a single drug,treatment with VPA+E2 or VPA+LG significantly increased the level of glycogen synthase kinase 3β,increased the expression of estrogen receptorα,reduced the expression of small ubiquitin-like modifiers,and increased the level of estrogen receptorβ.This resulted in enhanced sensitivity to estrogen therapy,reduced amyloidβaggregation,reduced abnormal phosphorylation of the tau protein,reduced neuronal loss,increased dendritic spine and postsynaptic density,and significantly alleviated memory loss and learning impairment in Alzheimer’s disease.This study was approved by the Chongqing Medical University Animal Protection and Ethics Committee,China on March 6,2013.
基金the National Natural Science Foundation of China,No.81300737the Natural Science Foundation of Liaoning Province of China,No.20180550524。
文摘BACKGROUND Posterior scleritis is a rare inflammatory ocular disease,characterized by severe and painful inflammation of the sclera.It is often misdiagnosed or underdiagnosed,due to its general and varying clinical presentation profile,which primarily involves pain and visual impairment but which can include eyelid edema,choroidal folds,serous retinal detachment,disc edema,hard exudates in fovea and subretinal mass.We report here a case of posterior scleritis,with symptoms of eye pain and red eye,initially misdiagnosed as acute conjunctivitis.CASE SUMMARY A 56-year-old man presented to a local hospital with complaint of pain and redness in the right eye.The initial diagnosis was acute conjunctivitis and he was given antibiotic eyedrops.Upon week-long continuance of the symptoms despite treatment,he presented to our hospital.Initial examination revealed a shallow anterior chamber in the right eye and vision reduction to 0.6.Further testing by optical coherence tomography,ultrasound biomicroscopy,and fundus photography indicated diagnosis of posterior scleritis.The patient was given methylprednisolone(oral)on a tapered reduction schedule(starting with 70 mg/d).According to the peaks and troughs of symptoms,compound betamethasone injection was administered into the bulb,culminating in discontinuation of the oral corticosteroid.Subsequent optical coherence tomography showed the subretinal fluid near the optic disc to be completely absorbed after treatment.CONCLUSION Posterior scleritis should be among the differential diagnosis of eye pain and redness,and diagnosis requires further ophthalmic accessory examination,such as by optical coherence tomography.
基金financially supported by the National Natural Science Foundation of China (Grant No.21671055)Henan University First-class Discipline Cultivation Project (Grant No.2020YLZDYJ06)+1 种基金Medical Interdisciplinary Training Program of Henan University of China (Grant No.CJ1205A0240007)the Scientific and Technological Project of Henan province (Grant No. 212102310852)
文摘In this paper,a new organic–inorganic hybrid compound[Co(L)_(2)]2[W_(6)O_(19)](1)(HL=2-acetylpyridine thiosemicarbazone)was prepared and characterized.The compound 1 exhibits remarkable antibacterial activity by determination of minimum inhibitory concentration(MIC)against Staphylococcus aureus(S.aureus,0.06μg·mL^(−1))and Escherichia coli(E.coli,0.24μg·mL^(−1)),respectively.Furthermore,the potential mechanism of compound 1 was studied in detail.The potential causes of bacteria death were cell wall/membrane disruption,inhibition of intracellular respiratory chain dehydrogenases(RCD)activity,destruction of reactive oxygen species(ROS)and depletion of glutathione(GSH).
