OBJECTIVE: Left ventricular remodeling induced by myocardial ischemia/reperfusion injury (MI/RI) is a common cardiac dysfunction. Accumulating evidence has demonstrated that autophagy plays a vital role in protecting against ventricular remodeling. This study aims to investigate the performance of Compound Danshen Tablets (CDT) in rescuing ventricular remodeling and whether autophagy as the potential mechanism. METHODS: The left anterior descending arteries of rats were temporarily ligated for 30 min to construct the MI/RI model. Ventricular remodeling was induced by reperfusion for 28 d, during which the MI/RI rats were administered CDT (300 mg/kg and 600 mg/kg), atorvastatin (2 mg/kg), and diltiazem (16 mg/kg). Cardiac function and structure were examined by echocardiography. Immunohistochemistry, Masson's trichrome staining, and hematoxylin-eosin (HE) staining were utilized to assess the fibrosis and histological alterations in the heart tissue. The expression of autophagy-related proteins was detected using Western blotting. RESULTS: CDT attenuated the cardiac dysfunction, structural changes, histopathological changes and fibrosis induced by MI/RI. CDT significantly enhanced the level of Beclin1 and microtubule-associated protein 1 light chain 3 beta (LC3β), and reduced p62 levels in MI/RI rats. Moreover, CDT significantly increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and inhibited mammalian target of rapamycin (mTOR) phosphorylation. CONCLUSION CDT ameliorated MI/RI-induced ventricular remodeling by activating autophagy and improving autophagic flux via the AMPK/mTOR signaling pathway.

BACKGROUND:Epidemiologic investigations and some experiments have shown that there is a close relationship between peripheral blood cells and osteoporosis,but the causal relationship between the two at the genetic level is still unclear. OBJECTIVE:To explore the causal relationship between peripheral blood cells and osteoporosis using Mendelian randomization methods. METHODS:Genome-wide association study data sets on peripheral blood cells,overall bone density at different ages,and calcaneal bone density were obtained from databases such as Blood Cell Consortium and MRC Integrative Epidemiology Unit. Blood cells were used as exposure data,with bone density at different ages and calcaneal bone density serving as outcome data. Mendelian randomization analyses were performed using methods such as inverse variance weighting,MR-Egger,weighted median method,and simple median. The results were assessed for heterogeneity,pleiotropy,and sensitivity using Cochran's Q,MR-Egger regression,and Leave-one-out method. The causal relationship between exposure and outcomes was evaluated using β values. RESULTS AND CONCLUSION:Due to the heterogeneity revealed by Cochran's Q test in the Mendelian randomization results,the results of the study were based on the inverse variance weighting method. The inverse variance weighting results showed that when age-specific bone density was used as an outcome,there was a negative causal relationship between white blood cell count and whole-body bone mineral density at the age of 45-60 years[β=-0.07,95％ confidence interval (CI):-0.13,-0.01,P=0.02],a positive causal relationship between monocyte count and whole-body bone mineral density at the age of 45-60 years (β=0.05,95％ CI:0.00,0.10,P=0.037),a negative causal relationship between white blood cell and basophil counts and whole-body bone mineral density over 60 years old (β=-0.04,95％ CI:-0.07,-0.01,P=0.005;β=-0.04,95％ CI:-0.07,-0.00,P=0.038),a positive causal relationship between hemoglobin concentration and hematocrit and whole-body bone mineral density over 60 years old (β=0.04,95％ CI:0.01,0.08,P=0.012;β=0.04,95％ CI:0.00,0.07,P=0.039),and a negative causal relationship between white cell count and whole-body bone mineral density at an undistinguished age (β=-0.10,95％ CI:-0.16,-0.03,P=0.002). When heel bone mineral density was used as an outcome,there was a negative causal relationship between white cell count and heel bone mineral density (β=-0.04,95％ CI:-0.07,-0.01,P=0.016),and a positive causal relationship between hemoglobin concentration and hematocrit and heel bone mineral density (β=0.05,95％ CI:0.01,0.08,P=0.007;β=0.05,95％ CI:0.01,0.08,P=0.004). To ensure the robustness of the results,meta-analyses of Mendelian randomization results of peripheral blood cells and whole-body bone mineral density as well as heel bone mineral density in different age groups were conducted. The results suggested that for every standard deviation decrease in log-transformed white blood cell count,there was a 5％ reduction in the risk of decreased bone mineral density (OR=0.95,95％ CI:0.94,0.97,P<0.001);whereas for every standard deviation increase in hemoglobin concentration and hematocrit,there was a 4％ reduction in the risk of decreased bone density (OR=1.04,95％ CI:1.03,1.06,P<0.001). In conclusion,increased white blood cell count in peripheral blood is a risk factor for bone mineral density;whereas increased hematocrit and hemoglobin concentration are protective factors for bone mineral density.

BACKGROUND:Epidemiologic investigations and some experiments have shown that there is a close relationship between peripheral blood cells and osteoporosis,but the causal relationship between the two at the genetic level is still unclear. OBJECTIVE:To explore the causal relationship between peripheral blood cells and osteoporosis using Mendelian randomization methods. METHODS:Genome-wide association study data sets on peripheral blood cells,overall bone density at different ages,and calcaneal bone density were obtained from databases such as Blood Cell Consortium and MRC Integrative Epidemiology Unit. Blood cells were used as exposure data,with bone density at different ages and calcaneal bone density serving as outcome data. Mendelian randomization analyses were performed using methods such as inverse variance weighting,MR-Egger,weighted median method,and simple median. The results were assessed for heterogeneity,pleiotropy,and sensitivity using Cochran's Q,MR-Egger regression,and Leave-one-out method. The causal relationship between exposure and outcomes was evaluated using β values. RESULTS AND CONCLUSION:Due to the heterogeneity revealed by Cochran's Q test in the Mendelian randomization results,the results of the study were based on the inverse variance weighting method. The inverse variance weighting results showed that when age-specific bone density was used as an outcome,there was a negative causal relationship between white blood cell count and whole-body bone mineral density at the age of 45-60 years[β=-0.07,95％ confidence interval (CI):-0.13,-0.01,P=0.02],a positive causal relationship between monocyte count and whole-body bone mineral density at the age of 45-60 years (β=0.05,95％ CI:0.00,0.10,P=0.037),a negative causal relationship between white blood cell and basophil counts and whole-body bone mineral density over 60 years old (β=-0.04,95％ CI:-0.07,-0.01,P=0.005;β=-0.04,95％ CI:-0.07,-0.00,P=0.038),a positive causal relationship between hemoglobin concentration and hematocrit and whole-body bone mineral density over 60 years old (β=0.04,95％ CI:0.01,0.08,P=0.012;β=0.04,95％ CI:0.00,0.07,P=0.039),and a negative causal relationship between white cell count and whole-body bone mineral density at an undistinguished age (β=-0.10,95％ CI:-0.16,-0.03,P=0.002). When heel bone mineral density was used as an outcome,there was a negative causal relationship between white cell count and heel bone mineral density (β=-0.04,95％ CI:-0.07,-0.01,P=0.016),and a positive causal relationship between hemoglobin concentration and hematocrit and heel bone mineral density (β=0.05,95％ CI:0.01,0.08,P=0.007;β=0.05,95％ CI:0.01,0.08,P=0.004). To ensure the robustness of the results,meta-analyses of Mendelian randomization results of peripheral blood cells and whole-body bone mineral density as well as heel bone mineral density in different age groups were conducted. The results suggested that for every standard deviation decrease in log-transformed white blood cell count,there was a 5％ reduction in the risk of decreased bone mineral density (OR=0.95,95％ CI:0.94,0.97,P<0.001);whereas for every standard deviation increase in hemoglobin concentration and hematocrit,there was a 4％ reduction in the risk of decreased bone density (OR=1.04,95％ CI:1.03,1.06,P<0.001). In conclusion,increased white blood cell count in peripheral blood is a risk factor for bone mineral density;whereas increased hematocrit and hemoglobin concentration are protective factors for bone mineral density.

Rabdosia serra(R.serra),an important component of Chinese herbal tea,has traditionally been used to treat hepatitis,jaundice,cholecystitis,and colitis.However,the chemical composition of R.serra and its effect against colitis remain unclear.In this study,the chemical composition of the water extract of R.serra was analyzed using ultra performance liquid chromatography coupled with a hybrid linear ion trap quadrupole-orbitrap mass spectrometer(UPLC-LTQ-Orbitrap-MS).A total of 46 compounds,comprising ent-kaurane diterpenoids,flavonoids,phenolic acids,and steroids,were identified in the water extract of R.serra,and the extract could significantly alleviate dextran sulfate sodium salt-induced colitis by improving colon length,upregulating anti-inflammatory factors,downregulating proinflammatory fac-tors,and restoring the balance of T helper 17/T regulatory cells.R.serra also preserved intestinal barrier function by increasing the level of tight junction proteins(zonula occludens 1 and occludin)in mouse colonic tissue.In addition,R.serra modulated the gut microbiota composition by increasing bacterial richness and diversity,increasing the abundance of beneficial bacteria(Muribaculaceae,Bacteroides,Lactobacillus,and Prevotellaceae_UCG-O01),and decreasing the abundance of pathogenic bacteria(Turi-cibacter,Eubacterium_fissicatena_group,and Eubacterium_xylanophilum_group).Gut microbiota depletion by antibiotics further confirmed that R.serra alleviated colitis in a microbiota-dependent manner.Overall,our findings provide chemical and biological evidence for the potential application of R.serra in the management of colitis.

Osteopontin (OPN) is a secreted O-glycosylated phosphoprotein that exists in a variety of tissues and body fluids, with a variety of biological activity. Integrin α_vβ_3 is the main receptor. OPN mainly involves in cell proliferation, differentiation, migration and adhesion. The study of OPN at home and abroad mainly focuses on the bone resorption, angiogenesis, atherosclerosis, digestive system, urinary system, wound healing, skin fibrosis, liver fibrosis, kidney fibrosis, etc.But reports about OPN in pulmonary fibrosis are much less, now the relationships between OPN and pulmonary fibrosis are reviewed.

Objective To study the molecular pathway of osteoblastic differentiation induced by substance P (SP), a neurotransmitter. Methods Mesenchymal stem cells were isolated and cultured, and treated with SP or its receptor (NK1) antagonist to induce osteoblastic cell differentiation, respectively. Alkaline phosphatase activity was determined; Osterix gene expression was detected by RT-PCR after 1-2 weeks for three times. The data of each culture condition were analyzed using SPSS12.0 statistical software to determine whether the differences between conditions were significant. Results After 4-5 days' culture, bone marrow stromal cells became spindle-shaped, triangular or polygonic. They covered the plate surface, formed extensive cell sheets in each group after 11-12 days of culture, and then induced differentiation to osteoblast. SP up-regulated the important transcription factor Osterix gene expression significantly (P<0.05). Conclusion The up-regulation of Osterix gene expression by SP may stimulate osteoblastic cell differentiation. SP's regulation depends on its receptor NK1.

Objective To explore the effects of neurotrophin-3 genetically modified Schwann cells(NT-3-SCs) and neural stem cells(NSCs) combinative transplantation to promote the neurons'survival and axonal regeneration of the spinal cord transected rat. Methods After the transected spinal cord injury(SCI) model was established in SD rats,NT-3-SCs or LacZ report gene modified Scwhann cells(LacZ-SCs) were combinative transplanted with NSCs into the transected site.60 days later,fluorogold(FG) was injected into the caudal spinal cord fo the transected site.7days after FG injected,the sacrifice,cryosection and morphology serious studies were performed to observe the FG labeled neurons in the rostral spinal cord(RSC) of transected site,red nuclei(RN) and the sensorimotor cortex(SMC);The survival neurons in the L_1 Clark's nuclei(CN),RN and SMC were couut,and regenerated axons within or near the transected spinal cord observed. Results From more to less,the order of groups of the survival neurons in the CN,RN and SMC was NT-3-SCS & NSCs group,LacZ-SCs & NSCs group,experimental control group.In the NT-3-SCs & NSCs group and LacZ-SCs & NSCs group,there were 5-HT,CGRP and SP positive axons within or near the transected spinal cord.And some FGlabeled cells were found in RSC,RN and SMC. Conclusion Combinative grafting NSCs and NT-3-SCs could promote the neurons'survival and axonal regeneration of the spinal cord injured rat.

AIM: To explore the effects of neurotrophin-3 (NT-3)-genetically modified Schwann cells (NT-3-SCs) on differentiation of neural stem cells (NSCs) into the neuron-like cells. METHODS: The NSCs were co-cultured with NT-3-SCs. Report gene LacZ genetically modified Schwann cells (LacZ-SCs) and normal SCs respectively in vitro. 7 d later, the differentiation of NSCs was studied by immunohistochemistry, and the percentage of neuron-like cells was calculated. RESULTS: NSCs differentiated to the GFAP-positive cells (glial-like cells) and NF-positive cells (neuron-like cells) in vitro. Compared to the normal SCs, NT-3-SCs more efficiently promoted NSCs to differentiate into the neuron-like cells. The effect of LacZ-SCs was as the same to the normal SCs. CONCLUSION: NT-3-SCs promote NSCs to differentiate into the neuron-like cells. [