Objective Using female mice to investigate the reparative effects of human umbilical cord mesenchymal stem cells on radiation-induced ovarian injury. Methods Mice were randomly divided into three groups: a blank control group, a radiation model group, and a cell therapy group. Mice in the radiation model group and the cell therapy group received a single whole-body irradiation of 5 Gy X-rays. Within 2 hours post-irradiation, mice in the cell therapy group underwent ovarian transplantation of UC-MSCs. On days 1, 7, and 14 post-irradiation, body weight was measured, ovarian index was calculated, histopathological changes in ovarian tissue were examined, serum levels of reproductive hormones (follicle-stimulating hormone, anti-Müllerian hormone, and estradiol) were determined, and the colonization of implanted UC-MSCs in the mice was observed. Results On days 1, 7, and 14 post-irradiation, both the cell therapy group and the radiation model group showed decreased body weight compared to the blank control group (P < 0.05). On day 1 post-irradiation compared to day 1 pre-irradiation within the same group, the radiation model group exhibited a greater decrease in body weight than the cell therapy group (P < 0.05). On days 1, 7, and 14 post-irradiation, the ovarian index decreased in both the radiation model group and the cell therapy group compared to the blank control group (P < 0.05). On days 7 and 14 post-irradiation, the ovarian index in the cell therapy group was significantly higher than that in the radiation model group (P < 0.05). Ovarian tissue in the radiation model group exhibited atrophy and a reduction in the number of follicles at all stages. In contrast, follicles in the cell therapy group were large and abundant. On days 1, 7, and 14 post-irradiation, serum follicle-stimulating hormone levels in the cell therapy group were lower than those in the radiation model group, while anti-Müllerian hormone and estradiol levels were higher than those in the radiation model group (P < 0.01). In vivo fluorescence imaging demonstrated that UC-MSCs successfully colonized the ovarian tissue on days 1, 7, and 14 after transplantation. Conclusion UC-MSCs exert a repair effect on radiation-induced ovarian injury in mice.

Diabetic nephropathy(DN)is a significant causative factor of end-stage renal disease globally,and its pathogenesis involves dysregulation of multiple cellular and hormonal pathways.Podocytes play crucial roles in the process of DN,with the extent of podocyte injury closely associated with key pathological manifestations of renal damage,such as proteinuria,glomerular filtration rate,and glomerulosclerosis.However,due to the complexity and interplay of mechanisms contributing to podocyte injury,such as oxidative stress,abnormal lipid metabolism,and mitochondrial damage,the precise mechanisms underlying podocyte injury remain incompletely understood.This review integrated the latest research findings from both domestic and international studies on the core mechanisms of podocyte injury in DN.Furthermore,this article summarized the implications of these mechanisms for DN treatment,particularly focusing on potential therapeutic targets and the development of related pharmacological interventions derived from targeting podocyte injury pathways,so as to provide a theoretical foundation for the development of clinical therapeutic strategies for DN.

Objective:To select low-dose radiation-activated genes with intrinsic radiation protection by developing a model for adaptive responses to low-dose ionizing radiation, in order to explore the mechanisms behind the radiation resistance of the candidate genes.Methods:The cells were divided into adaptive response induction group and whole transcriptome sequencing group. The level of DNA damage was assessed using the γ-H2AX immunofluorescence assay. The low-dose radiation-activated candidate genes with radiation protection were selected through whole transcriptome sequencing and quantitative reverse transcription PCR (RT-qPCR)-based validation. The anti-radiation effect of candidate gene CCND1 was assessed based on CCK-8 cell proliferation and γ-H2AX immunofluorescence assay. After up- and down-regulation of CCND1 expression, the anti-radiation mechanism of CCND1 was preliminarily explored through transcriptome sequencing analysis.Results:A model for low-dose ionizing radiation-induced adaptive responses of lymphocytes was constructed. Using this model, six candidate genes with radiation protection, including CCND1, ZMAT3, MGAT3, DFFB, CYP4F2, ITGA6, were selected. Compared to the control group, overexpressed CCND1 led to significantly enhanced proliferation ability of AHH-1 cells ( t = 7.92-14.76, P < 0.05) and distinctly lowered level of DNA damage ( t = 2.79-9.68, P < 0.05) after 2 Gy of X-ray irradiation. Furthermore, compared to the control group, the CCND1 knockdown caused significantly decreased cell proliferation ability ( t = 13.58-26.25, P < 0.05) and notably elevated level of DNA damage of cells ( t = 2.87-7.61, P < 0.05). Transcriptome sequencing revealed that up- and down-regulation of CCND1 expression resulted in the activation of pathways related to cell growth, death, and damage repair. Conclusions:By selecting six low-dose-activated candidate genes with radiation protection and revealing the function of CCND1 in radiation protection, this study provides a new perspective for the development of radiation protection agents from the perspective of adaptive responses to low-dose radiation.

Objective To observe the value of right ventricular free wall longitudinal strain(RVFWLS)to pulmonary artery systolic pressure(PASP)ratio(RVFWLS/PASP)for evaluating systolic function of right ventricle(RV)in patients with hypertrophic cardiomyopathy(HCM).Methods Fifty-two HCM patients were retrospectively collected and divided into group A(RVFWLS/PASP≤0.75,n=26)and B(RVFWLS/PASP＞0.75,n=26)according to median RVFWLS/PASP.Meanwhile,26 healthy individuals were included as control group.Parameters of echocardiography and speckle tracking imaging(STI)were obtained and compared among 3 groups.The correlations of RVFWLS/PASP and other parameters were analyzed with linear regression.Results In group A and B,left ventricular ejection fraction(LVEF),RV septal longitudinal strain(RVSepLS),RVFWLS,RV end-diastolic volume index(RVEDVi),RV stroke volume(RVSV),RV fractional area change(RVFAC)and left ventricular global longitudinal strain(LVGLS)were all lower,while the ratio of peak E blood flow velocity at mitral orifice diastole to early mitral intervalal annulus diastole velocity(E/e′)were higher than those in control group(all adjusted P＜0.05).Compared with group B and control group,group A had higher PASP but lower RV ejection fraction(RVEF)(all adjusted P＜0.05).Furthermore,RVFWLS and LVGLS were both lower in group A than in group B(both adjusted P＜0.05).Linear regression analysis showed that RVSepLS and RVEF were independently linearly related to RVFWLS/PASP(both P＜0.05).Conclusion RVFWLS/PASP could be used to monitor changes of RV systoic function in HCM patients at early stage.

Objective:To select low-dose radiation-activated genes with intrinsic radiation protection by developing a model for adaptive responses to low-dose ionizing radiation, in order to explore the mechanisms behind the radiation resistance of the candidate genes.Methods:The cells were divided into adaptive response induction group and whole transcriptome sequencing group. The level of DNA damage was assessed using the γ-H2AX immunofluorescence assay. The low-dose radiation-activated candidate genes with radiation protection were selected through whole transcriptome sequencing and quantitative reverse transcription PCR (RT-qPCR)-based validation. The anti-radiation effect of candidate gene CCND1 was assessed based on CCK-8 cell proliferation and γ-H2AX immunofluorescence assay. After up- and down-regulation of CCND1 expression, the anti-radiation mechanism of CCND1 was preliminarily explored through transcriptome sequencing analysis.Results:A model for low-dose ionizing radiation-induced adaptive responses of lymphocytes was constructed. Using this model, six candidate genes with radiation protection, including CCND1, ZMAT3, MGAT3, DFFB, CYP4F2, ITGA6, were selected. Compared to the control group, overexpressed CCND1 led to significantly enhanced proliferation ability of AHH-1 cells ( t = 7.92-14.76, P < 0.05) and distinctly lowered level of DNA damage ( t = 2.79-9.68, P < 0.05) after 2 Gy of X-ray irradiation. Furthermore, compared to the control group, the CCND1 knockdown caused significantly decreased cell proliferation ability ( t = 13.58-26.25, P < 0.05) and notably elevated level of DNA damage of cells ( t = 2.87-7.61, P < 0.05). Transcriptome sequencing revealed that up- and down-regulation of CCND1 expression resulted in the activation of pathways related to cell growth, death, and damage repair. Conclusions:By selecting six low-dose-activated candidate genes with radiation protection and revealing the function of CCND1 in radiation protection, this study provides a new perspective for the development of radiation protection agents from the perspective of adaptive responses to low-dose radiation.

Objective To observe the value of right ventricular free wall longitudinal strain(RVFWLS)to pulmonary artery systolic pressure(PASP)ratio(RVFWLS/PASP)for evaluating systolic function of right ventricle(RV)in patients with hypertrophic cardiomyopathy(HCM).Methods Fifty-two HCM patients were retrospectively collected and divided into group A(RVFWLS/PASP≤0.75,n=26)and B(RVFWLS/PASP＞0.75,n=26)according to median RVFWLS/PASP.Meanwhile,26 healthy individuals were included as control group.Parameters of echocardiography and speckle tracking imaging(STI)were obtained and compared among 3 groups.The correlations of RVFWLS/PASP and other parameters were analyzed with linear regression.Results In group A and B,left ventricular ejection fraction(LVEF),RV septal longitudinal strain(RVSepLS),RVFWLS,RV end-diastolic volume index(RVEDVi),RV stroke volume(RVSV),RV fractional area change(RVFAC)and left ventricular global longitudinal strain(LVGLS)were all lower,while the ratio of peak E blood flow velocity at mitral orifice diastole to early mitral intervalal annulus diastole velocity(E/e′)were higher than those in control group(all adjusted P＜0.05).Compared with group B and control group,group A had higher PASP but lower RV ejection fraction(RVEF)(all adjusted P＜0.05).Furthermore,RVFWLS and LVGLS were both lower in group A than in group B(both adjusted P＜0.05).Linear regression analysis showed that RVSepLS and RVEF were independently linearly related to RVFWLS/PASP(both P＜0.05).Conclusion RVFWLS/PASP could be used to monitor changes of RV systoic function in HCM patients at early stage.

Objective To investigate the factors affecting the prognosis of endovascular treatment(EVT)for acute vertebrobasilar artery occlusion(AVBAO)within 24 h of onset of disease.Methods General and clinical data of AVBAO patients admitted to the Department of Cerebrovascular Diseases,Henan Provincial People's Hospital who received EVT within 24h of onset from October 2020 to September 2023 were retrospectively and consecutively included,including age,sex,stroke-related risk factors(hyperlipidemia,hypertension,diabetes mellitus,atrial fibrillation,coronary artery disease,smoking,and previous stroke),preoperative National Institutes of Health stroke scale(NIHSS)score,preoperative modified Rankin scale(mRS)score,form of onset,preoperative intravenous thrombolysis,posterior circulation Alberta stroke program early CT score(pc-ASPECTS),basilar artery on computed tomography angiography(BATMAN)score,site of occlusion(intracranial segment of vertebral artery,basilar artery),and surgical procedure(direct aspiration and/or stent-retrieval,balloon dilatation,stenting,etc.First-line stenting or balloon dilatation is direct angioplasty;if blood flow cannot be maintained after thrombectomy,further balloon dilatation and/or stenting is required as remedial angioplasty),onset-to-puncture time,puncture-to-recanalization time,and postprocedure immediate modified thrombolysis in cerebral infarction(mTICI)grading(successful recanalization was defined as mTICI grading 2b or 3),and perioperative complications(intraprocedural thrombus migration,intraprocedural reocclusion,intraprocedural dissection,postoperative hemorrhagic transformation within 3 d,and symptomatic intracranial hemorrhage[sICH]).Patient prognosis was assessed by mRS score at 90 d postoperatively.The mRS score≤3 was classified as good prognosis,and mRS score＞3 was classified as poor prognosis.Indicators with P＜0.1 in the results of univariate analysis were included,and variables were screened by backward elimination and subjected to multifactorial Logistic regression analysis to analyze the factors influencing the prognosis of AVBAO patients undergoing EVT within 24 h of the onset of the disease.Results A total of 149 AVBAO patients who underwent EVT were included,including 79 patients with good prognosis,70 patients with poor prognosis,145 patients with successful revascularization,34 patients with perioperative complications,and 32 patients with death.(1)The results of univariate analysis showed that compared with patients with poor prognosis,patients with good prognosis had lower preoperative NIHSS scores(16.0[12.0,23.0]vs.24.5[16.8,31.3],Z=-4.280,P＜0.01)and preoperative mRS scores(4[4,4]vs.5[4,5],Z=-4.711,P＜0.01),a lower percentage of diabetes mellitus(15.2％[12/79]vs.35.7％[25/70],x2=8.376,P=0.004),and the incidence of postoperative hemorrhagic transformation within 3d(7.6％[6/79]vs.25.7％[18/70],x2=-0.246,P=0.003)and the incidence of sICH(1.3％[1/79]vs.14.3％[10/70],x2=-0.249,P=0.002)were significantly lower in patients with good prognosis than that in patients with poor prognosis.(2)Age,hyperlipidemia,diabetes mellitus,preoperative NIHSS score,preoperative mRS score,postoperative hemorrhagic transformation within 3 d and sICH were included in multifactorial Logistic regression analysis,which showed that hyperlipidemia(OR,2.433,95％CI 1.088-5.441),diabetes mellitus(OR,2.797,95％CI 1.168-6.701),high preoperative NIHSS score(OR,3.715,95％CI 1.684-8.195),and postoperative sICH within 3 d(OR,19.681,95％CI 1.984-195.192)were the independent risk factors for poor prognosis of patients with AVBAO who underwent EVT within 24 h of onset(all P＜0.05).Conclusion Hyperlipidemia,diabetes mellitus,high preoperative NIHSS score,and postoperative sICH within 3 d were independent risk factors for poor prognosis in AVBAO patients who underwent EVT within 24 h of onset.

Objective To investigate the factors affecting the prognosis of endovascular treatment(EVT)for acute vertebrobasilar artery occlusion(AVBAO)within 24 h of onset of disease.Methods General and clinical data of AVBAO patients admitted to the Department of Cerebrovascular Diseases,Henan Provincial People's Hospital who received EVT within 24h of onset from October 2020 to September 2023 were retrospectively and consecutively included,including age,sex,stroke-related risk factors(hyperlipidemia,hypertension,diabetes mellitus,atrial fibrillation,coronary artery disease,smoking,and previous stroke),preoperative National Institutes of Health stroke scale(NIHSS)score,preoperative modified Rankin scale(mRS)score,form of onset,preoperative intravenous thrombolysis,posterior circulation Alberta stroke program early CT score(pc-ASPECTS),basilar artery on computed tomography angiography(BATMAN)score,site of occlusion(intracranial segment of vertebral artery,basilar artery),and surgical procedure(direct aspiration and/or stent-retrieval,balloon dilatation,stenting,etc.First-line stenting or balloon dilatation is direct angioplasty;if blood flow cannot be maintained after thrombectomy,further balloon dilatation and/or stenting is required as remedial angioplasty),onset-to-puncture time,puncture-to-recanalization time,and postprocedure immediate modified thrombolysis in cerebral infarction(mTICI)grading(successful recanalization was defined as mTICI grading 2b or 3),and perioperative complications(intraprocedural thrombus migration,intraprocedural reocclusion,intraprocedural dissection,postoperative hemorrhagic transformation within 3 d,and symptomatic intracranial hemorrhage[sICH]).Patient prognosis was assessed by mRS score at 90 d postoperatively.The mRS score≤3 was classified as good prognosis,and mRS score＞3 was classified as poor prognosis.Indicators with P＜0.1 in the results of univariate analysis were included,and variables were screened by backward elimination and subjected to multifactorial Logistic regression analysis to analyze the factors influencing the prognosis of AVBAO patients undergoing EVT within 24 h of the onset of the disease.Results A total of 149 AVBAO patients who underwent EVT were included,including 79 patients with good prognosis,70 patients with poor prognosis,145 patients with successful revascularization,34 patients with perioperative complications,and 32 patients with death.(1)The results of univariate analysis showed that compared with patients with poor prognosis,patients with good prognosis had lower preoperative NIHSS scores(16.0[12.0,23.0]vs.24.5[16.8,31.3],Z=-4.280,P＜0.01)and preoperative mRS scores(4[4,4]vs.5[4,5],Z=-4.711,P＜0.01),a lower percentage of diabetes mellitus(15.2％[12/79]vs.35.7％[25/70],x2=8.376,P=0.004),and the incidence of postoperative hemorrhagic transformation within 3d(7.6％[6/79]vs.25.7％[18/70],x2=-0.246,P=0.003)and the incidence of sICH(1.3％[1/79]vs.14.3％[10/70],x2=-0.249,P=0.002)were significantly lower in patients with good prognosis than that in patients with poor prognosis.(2)Age,hyperlipidemia,diabetes mellitus,preoperative NIHSS score,preoperative mRS score,postoperative hemorrhagic transformation within 3 d and sICH were included in multifactorial Logistic regression analysis,which showed that hyperlipidemia(OR,2.433,95％CI 1.088-5.441),diabetes mellitus(OR,2.797,95％CI 1.168-6.701),high preoperative NIHSS score(OR,3.715,95％CI 1.684-8.195),and postoperative sICH within 3 d(OR,19.681,95％CI 1.984-195.192)were the independent risk factors for poor prognosis of patients with AVBAO who underwent EVT within 24 h of onset(all P＜0.05).Conclusion Hyperlipidemia,diabetes mellitus,high preoperative NIHSS score,and postoperative sICH within 3 d were independent risk factors for poor prognosis in AVBAO patients who underwent EVT within 24 h of onset.

Early weaned piglets suffer from oxidative stress and enteral infection, which usually results in gut microbial dysbiosis, serve diarrhea, and even death. Rice bran oil (RBO), a polyphenol-enriched by-product of rice processing, has been shown to have antioxidant and anti-inflammatory properties both in vivo and in vitro. Here, we ascertained the proper RBO supplementation level, and subsequently determined its effects on lipopolysaccharide (LPS)-induced intestinal dysfunction in weaned piglets. A total of 168 piglets were randomly allocated into four groups of seven replicates (42 piglets each group, (21±1) d of age, body weight (7.60±0.04) kg, and half males and half females) and were given basal diet (Ctrl) or basal diet supplemented with 0.01% (mass fraction) RBO (RBO1), 0.02% RBO (RBO2), or 0.03% RBO (RBO3) for 21 d. Then, seven piglets from the Ctrl and the RBO were treated with LPS (100 μg/kg body weight (BW)) as LPS group and RBO+LPS group, respectively. Meanwhile, seven piglets from the Ctrl were treated with the saline vehicle (Ctrl group). Four hours later, all treated piglets were sacrificed for taking samples of plasma, jejunum tissues, and feces. The results showed that 0.02% was the optimal dose of dietary RBO supplementation based on diarrhea, average daily gain, and average daily feed intake indices in early weaning piglets. Furthermore, RBO protected piglets against LPS-induced jejunal epithelium damage, which was indicated by the increases in villus height, villus height/crypt depth ratio, and Claudin-1 levels, as well as a decreased level of jejunal epithelium apoptosis. RBO also improved the antioxidant ability of LPS-challenged piglets, which was indicated by the elevated concentrations of catalase and superoxide dismutase, and increased total antioxidant capacity, as well as the decreased concentrations of diamine oxidase and malondialdehyde in plasma. Meanwhile, RBO improved the immune function of LPS-challenged weaned piglets, which was indicated by elevated immunoglobulin A (IgA), IgM, β‍‍-defensin-1, and lysozyme levels in the plasma. In addition, RBO supplementation improved the LPS challenge-induced dysbiosis of gut microbiota. Particularly, the indices of antioxidant capacity, intestinal damage, and immunity were significantly associated with the RBO-regulated gut microbiota. These findings suggested that 0.02% RBO is a suitable dose to protect against LPS-induced intestinal damage, oxidative stress, and jejunal microbiota dysbiosis in early weaned piglets.
Male ; Female ; Swine ; Animals ; Lipopolysaccharides/toxicity* ; Antioxidants/pharmacology* ; Rice Bran Oil ; Dysbiosis ; Dietary Supplements ; Diarrhea/veterinary* ; Weaning ; Body Weight

Resveratrol (RES), a natural polyphenolic phytochemical, has been suggested as a putative anti-aging molecule for the prevention and treatment of Alzheimer's disease (AD) by the activation of sirtuin 1 (Sirt1/Sir2). In this study, we tested the effects of RES and Sirt1/Sir2 on sleep and courtship memory in a Drosophila model by overexpression of amyloid precursor protein (APP), whose duplications and mutations cause familial AD. We found a mild but significant transcriptional increase of Drosophila Sir2 (dSir2) by RES supplementation for up to 17 days in APP flies, but not for 7 days. RES and dSir2 almost completely reversed the sleep and memory deficits in APP flies. We further demonstrated that dSir2 acts as a sleep promotor in Drosophila neurons. Interestingly, RES increased sleep in the absence of dSir2 in dSir2-null mutants, and RES further enhanced sleep when dSir2 was either overexpressed or knocked down in APP flies. Finally, we showed that Aβ aggregates in APP flies were reduced by RES and dSir2, probably via inhibiting Drosophila β-secretase (dBACE). Our data suggest that RES rescues the APP-induced behavioral deficits and Aβ burden largely, but not exclusively, via dSir2.
Animals ; Alzheimer Disease/metabolism* ; Amyloid beta-Peptides ; Amyloid beta-Protein Precursor/metabolism* ; Drosophila/physiology* ; Drosophila Proteins/metabolism* ; Resveratrol/pharmacology* ; Sirtuin 1 ; Sleep