BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.

Emerging research suggests a potential association of progression of Alzheimer's disease(AD)with al-terations in synaptic currents and mitochondrial dynamics.However,the specific associations between these pathological changes remain unclear.In this study,we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro models.The investigations included behavioural tests,brain magnetic resonance imaging(MRI),liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)analysis,Nissl staining,thioflavin-S staining,enzyme-linked immunosorbent assay,Golgi-Cox staining,trans-mission electron microscopy(TEM),immunofluorescence staining,proteomics,adenosine triphosphate(ATP)detection,mitochondrial membrane potential(MMP)and reactive oxygen species(ROS)assess-ment,mitochondrial morphology analysis,electrophysiological studies,Western blotting,and molecular docking.The results revealed changes in synaptic currents,mitophagy,and mitochondrial dynamics in the AD models.Remarkably,intervention with Dengzhan Shengmai(DZSM)capsules emerged as a pivotal element in this investigation.Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention,which notably amplified the frequency and amplitude of synaptic transmission.The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions,including the hippocampal CA3,primary cingular cortex,prelimbic system,and dysgranular insular cortex.DZSM intervention led to increased IDE levels,augmented long-term potential(LTP)amplitude,and enhanced dendritic spine density and length.Moreover,DZSM intervention led to favourable changes in mitochondrial parameters,including ROS expression,MMP and ATP contents,and mitochondrial morphology.In conclusion,our findings delved into the realm of altered synaptic currents,mitophagy,and mitochondrial dynamics in AD,concurrently highlighting the therapeutic potential of DZSM intervention.

Objectives:This study aims to investigate the association between cumulative fasting blood glucose(FBG)and presence of coronary artery calcification(CAC). Methods:A total of 1 113 participants were recruited from the Beijing Community-based Cohort of Atherosclerosis.Anthropometric measurements and laboratory examinations including FBG were performed in 1998,2008-2009 and 2013-2014 respectively,and coronary CT scan was performed in 2013-2014.Participants were classified into 4 groups according to the level of cumulative FBG(10-year weighted cumulative value of at least 2 FBGs):<50.0 mmol/L group(n=495),50.0-55.9 mmol/L group(n=345),56.0-69.9 mmol/L group(n=176),and≥70.0 mmol/L group(n=97).CAC score>0 was defined as presence of CAC.Multivariable logistic regression model was applied to analyze the impact of cumulative FBG exposure on the risk of CAC,and subgroup analyses were conducted according to factors such as sex and age. Results:The mean age of enrolled participants was(59.7±6.4)years,523(47.0%)were male and 478(42.9%)had CAC.The proportion of subjects with CAC increased with the increment of cumulative FBG.Compared with the<50.0 mmol/L group,the multivariable-adjusted OR(95%CI)for CAC in the 50.0-55.9 mmol/L group,56.0-69.9 mmol/L group,and≥70.0 mmol/L group were 1.43(1.04-1.98),1.92(1.24-2.99)and 2.79(1.35-5.77),respectively(Ptrend<0.05).The risk for CAC increased by 34%per 10 mmol/L increase in cumulative FBG,with OR(95%CI)of 1.34(1.12-1.59).There was no statistically significant difference in the risk of CAC presence for each 10 mmol/L increase in cumulative FBG level between the subgroups(all P≥0.05). Conclusions:Elevated cumulative FBG is a risk factor for the prevalence of CAC,indicating the importance of maintaining healthy FBG in preventing the occurrence of CAC.

Chronic inflammation induced by Helicobacter pylori is considered to be one of the main causes of gastric cancer,and CagA is a main virulence factor of H.pylori.The study aimed to investigate the role and mechanism of CagA in host inflammatory response.Mass spectrometry was used to identify the interacting proteins of CagA in AGS cells.By immunoprecipitation and immunofluorescence,the interaction was validated.Pathway expression was detected by immunoblotting after knockdown by using siRNA,and mRNA levels of inflammatory cytokines were detected by quantitative PCR.CagA-induced inflammatory responses were detected in clinical samples using hemoglobin-eosin staining(H&E).Data showed that CagA interacted with SHARPIN.And CagA activated the NF-κB signaling pathway and upregulated the mRNA and protein levels of the inflammatory cytokines IL-6,IL-8,and TNF-α,as compared with the CagA knockout strain(all P<0.05).Knockdown of SHARPIN by siRNA reduced inflammation levels and partially inhibit NF-κB signaling.In clinical samples,CagA-positive samples exhibited stronger inflammatory responses.To sum up,CagA promoted the host inflammatory response,and CagA-induced inflammatory response was reduced when SHARPIN was partially inhibited,suggesting that CagA activates the NF-κB signaling pathway through binding to SHARPIN.

BACKGROUND/OBJECTIVES: This study examined the relationship between famine exposure in early life and the risk of type 2 diabetes in adulthood during the 1959–1961 Chinese Famine. SUBJECTS/METHODS: A total of 3,418 individuals aged 35–74 years free of diabetes from two studies in 2006 and 2009 were followed up prospectively in 2009 and 2012, respectively. Famine exposure was classified as unexposed (individuals born in 1962–1978), fetal exposed (individuals born in 1959–1961), child exposed (individuals born in 1949–1958), and adolescent/adult exposed (born in 1931–1948). A logistic regression model was used to assess the relationship between famine exposure and diabetes after adjustment for potential covariates. RESULTS: During a three-year follow-up, the age-adjusted incidence rates of type 2 diabetes were 5.7%, 14.5%, 12.7%, and 17.8% in unexposed, fetal-exposed, child-exposed, and adolescent/adult-exposed groups, respectively (P < 0.01). Relative to the unexposed group, the relative risks (95% confidence interval) for diabetes were 2.15 (1.29–3.60), 1.53 (0.93– 2.51), and 1.65 (0.75–3.63) in the fetal-exposed, child-exposed, and adolescent/adult-exposed groups, after controlling for potential covariates. The interactions between famine exposure and obesity, education level, and family history of diabetes were not observed, except for the urbanization type. Individuals living in rural areas with fetal and childhood famine exposure were at a higher risk of type 2 diabetes, with relative risks of 8.79 (1.82–42.54) and 2.33 (1.17–4.65), respectively. CONCLUSIONS These findings indicate that famine exposure in early life is an independent predictor of type 2 diabetes, particularly in women. Early identification and intervention may help prevent diabetes in later life.

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) on mental state, visceral sensitivity and protein expression of nerve growth factor (NGF), tyrosine kinase receptor A (TrkA) and transient receptor potential vanilloid 1 (TRPV1) of colonic tissue in diarrhea-predominant irritable bowel syndrome (IBS-D) rats, and to explore its possible mechanism on treating IBS-D. METHODS: A total of 36 male SD rats of SPF grade were randomized into a blank group, a model group, an EA group and a western medication group, 9 rats in each group. In the model group, the EA group and the western medication group, IBS-D model was established by enema of dinitrobenzene sulfonic acid (DNBS) combined with chronic restraint stress method. In the EA group, EA was applied at "Tianshu" (ST 25) and "Shangjuxu" (ST 37), with disperse-dense wave, in frequency of 2 Hz/100 Hz, 20 min each time, once a day for 7 days. In the western medication group, pinaverium bromide suspension was given by gavage (15 mg•kg^-1•d^-1) for 7 days. Before and after model establishment, and after intervention, the body mass, 24 h food intake and fecal water content were observed, the visceral sensitivity was detected by abdominal withdrawal reflex (AWR); after intervention, the mental state was evaluated by elevated plus maze (EPM) test, the protein expression of NGF, TrkA and TRPV1 was detected by immunohistochemistry and Western blot in the 4 groups. RESULTS: After model establishment, compared with the blank group, the body mass and 24 h food intake were decreased (P<0.05), first systolic latency of AWR was shortened and number of contraction wave of AWR was increased (P<0.05), and fecal water content was increased (P<0.05) in the model group, the EA group and the western medication group. After intervention, compared with the blank group, open arm residence time ratio (OT%) of EPM was decreased (P<0.05) and protein expression of NGF, TrkA, TRPV1 in colonic tissue was increased in the model group (P<0.05); compared with the model group, the body mass and 24 h food intake were increased (P<0.05), first systolic latency of AWR was lengthened and number of contraction wave of AWR was decreased (P<0.05), the fecal water content was decreased (P<0.05), OT% of EPM was increased (P<0.05), and protein expression of NGF, TrkA, TRPV1 in colonic tissue was decreased (P<0.05) in the EA group and the western medication group. CONCLUSION Electroacupuncture at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) can relieve the anxiety and depression-like behaviors in IBS-D rats, down-regulate the protein expression of NGF, TrkA, TRPV1 in colonic tissue, so as to reduce the visceral sensitivity and relieve symptoms.
Male ; Rats ; Animals ; Receptor Protein-Tyrosine Kinases ; Rats, Sprague-Dawley ; Irritable Bowel Syndrome/therapy* ; Sulfonic Acids ; Nerve Growth Factors ; TRPV Cation Channels/genetics*

Background: Disrupted circadian rhythms have been associated with the development of irritable bowel syndrome (IBS). In some IBS patients, the symptoms may present with circadian fluctuations. Enterochromaffin cells (EC cells) and tryptophan hydroxylase 1 (TPH1) - 5 - hydroxytryptamine (5 - HT) signaling pathway are currently recognized as the key pathophysiological mechanism of IBS. Aims: To explore whether Bmal1, the core circadian clock gene, is involved in the occurrence of IBS by regulating TPH1-5-HT signaling pathway in EC cells. Methods: Normal Sprague-Dawley (SD) rats and IBS-model SD rats, as well as wild type (WT) and intestine-specific Bmal1 knockout (Bmal1

Adult ; Atherosclerosis ; Cardiovascular Diseases ; China ; Habits ; Humans ; Lipids

Objective To evaluate the feasibility of dual-source low-dose computed tomography (CT) of the paranasal sinus in children, with acquisition at an ultra-low tube voltage (70 kVp) combined with the Flash scan. Methods CT scans of the paranasal sinus were performed on 80 pediatric patients who were divided into two groups according to different protocols (70 kVp protocol with Flash scan mode and the iterative reconstruction, pitch 3, the experimental group (group A), n = 40; 80 kVp protocol with conventional spiral mode, pitch 1.5, control group (group B), n = 40). For each examination, the CT dose index (CTDIvol), dose-length product (DLP) and effective dose (ED) were estimated. The image noise, signal-to-noise ratio (SNR) and overall subjective diagnostic image quality were also evaluated. Results The images of these two groups were all satisfied for the clinical diagnosis. For radiation dose, the CTDIvol (mGy), DLP (mGycm) and ED (mSv) values of the 70 kVp protocol were significantly lower than those of the 80 kVp protocol [CTDIvol: 0.39 ± 0.004 vs1.57 ± 0.009 mGy, P < 0.001; DLP: 6.31 ± 0.52 vs 19.88 ± 2.01 mGycm, P < 0.001; ED: 0.024 ± 0.005 vs 0.079 ± 0.016 mSv, P < 0.001. Compared with those of the 80-kVp protocol, the image noise and the SNR_bone increased, the SNR_soft-tissue decreased. There was no statistical difference in the subjective scores of the two groups of image quality by the two physicians (P > 0.05). Conclusion When diagnosing the paranasal sinus in children, an ultralow tube voltage (70 kVp) combined with the Flash scan technique can reduce the radiation dose significantly while maintaining diagnostic image quality with clinically acceptable image noise.