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: ObjectiveHeat shock proteins (HSPs) are cytoprotective proteins. Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor. This study aimed to elucidate the possible role of cytoprotection and angiogenesis on cardiac function after bone marrow cell transplantation (BMT).: MethodsMyocardial infarction was induced in inbred Lewis rats by left anterior descending artery ligation. A total of 5×106 bone marrow-mononuclear cells were transplanted into the ischemic zone by direct injection. At 1, 3, 7, 14 and 28 days post-transplantation, cardiac function was evaluated by echocardiography. The expressions of HSP32, HSP70 and VEGF were assessed by immunofluorescence and RT-PCR. The number of vessels was examined by immunohistochemistry. The differentiation of the transplanted cells was determined by immunofluorescence.: ResultsEchocardiography showed BMT led to sustained improvement in cardiac function, as assessed by left ventricle ejection fraction and fraction of shortening. Immunofluorescence revealed that the expressions of HSP32, HSP70 and VEGF were promoted in both transplanted bone marrow cells and recipient cardiomyocytes. RT-PCR showed that the mRNA expression levels of HSP32, HSP70 and VEGF in the BMT group were markedly higher in comparison with injection of peripheral blood cells or saline (P<0.01) by day 7. Seven days later, the vessel count showed that angiogenesis had been induced to a significantly greater degree in the BMT groups. Fourteen days later, specific markers for myocardial or vascular endothelial cells were detected in the transplanted bone marrow cells.: ConclusionsBMT upregulated the expressions of HSP32, HSP70 and VEGF in both transplanted bone marrow cells and recipient endogenous cardiomyocytes in the early phase post-transplantation. This enhanced cytoprotection and angiogenesis, and contributed to the functional recovery following cardiac infarction. In the late phase, the transplanted bone marrow cells might differentiate into both myocardial and vascular endothelial cells that enhanced the ischemic cardiac function further. [Copyright &y& Elsevier]

Background: Osteoarthritis (OA) is common in the elderly. Baicalin (BA) is a flavonoid monomer extracted from Scutellaria baicalensis Georgi , which has been reported to have anti-inflammatory, anti-deformation and anti-bacterial effects., Methods: Cultures of micromass and 3D alginate beads, Alcian blue and Safranin O (SO)/fast green staining were used to investigate chondrocyte viability and extracellular matrix (ECM) synthesis in chondrocytes of all groups. The expression of SOX9, Smad3, Aggrecan (ACAN), type II collagen (Col2α), matrix metallopetidase 9 (MMP9), MMP13 and ADAMTS5 in chondrocytes of all groups were detected by western blot or qRT-PCR., Results: The present study demonstrates that BA neutralized the IL-1β-induced downregulation of chondrocyte viability and ECM secretion, including ACAN and Col2α. The downregulation of SOX9, and the upregulation of MMP9, MMP13 and ADAMTS5 induced by IL-1β were reversed by BA treatment. Moreover, BA increased the nuclear translocation of Smad3 and SOX9 in chondrocytes cultured by micromass and 3D alginate beads. Interestingly, Smad3 inhibitor SIS3 reversed the promoting effect of BA on chondrocyte viability, ECM secretion, SOX9 and Smad3 nuclear translocation, and the inhibiting effect of BA on MMP9 and ADAMTS5 expressions. BA treatment also attenuated the decrease of Smad3 phosphorylation, SOX9 expression and the damage of cartilage integrity in mice which were induced by destabilization of the medial meniscus (DMM)., Conclusion: BA promotes chondrocyte viability and the cell matrix synthesis through TGF-β/Smad3 pathway in IL-1β-treated chondrocytes and DMM treated mice. BA is a potential therapeutic target for OA., Competing Interests: None., (AJTR Copyright © 2021.)

Background: Gastroesophageal varices is a serious complication of compensated advanced chronic liver disease (cACLD). Primary prophylaxis to reduce the risk of variceal hemorrhage is recommended if high-risk varices (HRV) are detected. We performed this study to compare the accuracy, patients' satisfaction and safety of detection of HRV by detachable string magnetically controlled capsule endoscopy (DS-MCCE) with esophagogastroduodenoscopy (EGD) as the reference., Methods: We prospectively recruited participants with cACLD from 12 university hospitals (11 in China and one in the United Kingdom) between November 2018 and December 2019 (ClinicalTrials.gov, NCT03749954). All participants underwent DS-MCCE, followed by EGD within a week in a blinded fashion. Following endoscopy, and on the same day, participants were asked to fill in a satisfaction questionnaire regarding their experience., Findings: A total of 105 eligible participants were enrolled. With EGD as the reference standard, the concordance index, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of DS-MCCE in diagnosis of HRV were 0•90 (95% confidence interval [CI]: 0•83-0•95), 92% (95% CI: 78-98%), 88% (95% CI: 78-95%), 80% (95% CI: 70-92%), 95% (95% CI: 90-100%), 7•91 (95% CI: 4•10-15•30), and 0•09 (95% CI: 0•03-0•30), respectively. The kappa score of 0•78 (95% CI: 0•65-0•90) suggested substantial agreement between DS-MCCE and EGD. Moreover, in participants undergoing EGD without sedation, the satisfaction of DS-MCCE was significantly better than that of EGD ( p < 0•0001, d  = 1•15 [95%CI: 0•88-1•42]). All participants confirmed the excretion of the capsule, and no adverse events occurred., Interpretation: DS-MCCE is an accurate alternative to EGD for detecting HRV in cACLD, which is safe and associated with better satisfaction., Funding: A full list of funding can be found in the Funding Support section., Competing Interests: The authors have declared no conflict of interests related to the study., (© 2020 The Authors.)

Objective: To investigate the changes in fecal flora and its correlation with the occurrence and progression of inflammatory bowel disease (IBD)., Methods: We collected fresh fecal specimens from 167 IBD patients (including 113 with ulcerative colitis and 54 with Crohn's disease) and 54 healthy volunteers. The fecal flora was analyzed by gradient dilution method and the data of inflammatory markers including WBC, PLT, CRP and ESR were collected to assess the association between the fecal flora and the inflammatory markers., Results: The species Enterrococcus (6.60∓0.23, P<0.01), Saccharomyces (2.22∓0.27, P<0.05), Bacteriodes (5.57∓0.28, P<0.001), Bifidobacterium (5.08∓0.30, P<0.01), Peptococcus (6.22∓0.25, P<0.001), Lactobacillus (6.00∓0.26, P<0.001), and Clostridium (3.57∓0.30, P<0.05) all increased significantly, while Eubacterium (1.56∓0.24, P<0.01) reduced markedly in patients with ulcerative colitis compared with those in the control subjects. Enterrococcus (6.93∓0.28, P<0.01), Saccharomyces (2.73∓0.37, P<0.01), Bacteriodes (4.32∓0.52, P<0.05), Bifidobacterium (4.88∓0.42, P<0.05), Peptococcus (6.19∓0.32, P<0.01) and Lactobacillus (4.73∓0.47, P<0.001) all increased significantly and Eubacterium (1.01∓0.29, P<0.01) and Clostridium (0.87∓0.31, P<0.01) decreased in patients with Crohn's disease. The positivity rates of bacterial culture were consistent with the results of quantitative analysis of the fecal flora. The changes in fecal flora did not show a significant correlation with these inflammatory markers., Conclusion: IBD patients have fecal flora imbalance compared with the healthy controls, and this imbalance may contribute to the occurrence and progression of IBD. The decline of Eubacterium contributes to the occurrence and development of IBD.

Objective: The chemokine stromal cell-derived factor-1 (SDF-1) has been implicated in homing of bone marrow cells to sites of injury. We investigated the time course of myocardial SDF-1 expression and effects of intravenously administered bone marrow mesenchymal stem cells (MSC) in rats with myocardial infarction (MI)., Methods: SDF-1 expression was measured by RT-PCR and Western blot in sham operated or infarcted hearts at 1/2, 1, 2, 4, 8 and 16 days post operation. MSCs from donor rats were labeled with BrdU. A total of 5 x 10(6) cells in 2.5 mL of PBS or equal volume PBS alone were injected through the tail vein at above mentioned time points. The number of the labeled MSCs in the infarcted hearts was counted 3 days post injection. Cardiac function and vessel numbers were assessed 28 days post injection., Results: Myocardial SDF-1 expression increased and peaked at the first day and decreased thereafter post MI and remained unchanged in sham operated hearts. The MSCs enrichment and angiogenesis in the host hearts were more abundant in the 1 day transplantation group than in the other groups (P < 0.01). Cardiac function was only improved in rats received intravenous MSCs injection within 4 days post MI and not affected by PBS injection., Conclusions: Myocardial SDF-1 expression was increased only in the early phase post MI. MSCs intravenous infused at the early phase of MI were recruited to injured heart, enhanced angiogenesis and improved cardiac function.

Objective: To clarify the role of Heat shock proteins (HSPs) on the cardiac function during acute myocardial infarction (AMI) after bone marrow cell implantation (BMT), we examined the expression of HSP32 and HSP70 in a rat model of myocardial infarction., Methods: Myocardial infarction model was induced in the inbred Lewis rats by left anterior descending artery ligation, and 5 x 10(6) of bone marrow-mononuclear cells (BM-MNCs) were injected into an ischemic zone. On days 1, 3, 7 and 14 post-infarct, the differentiations of transplanted cells and the expressions of HSP32 and HSP70 were determined by immunofluorescence or RT-PCR. The cardiac function was evaluated by echocardiography., Results: Immunofluorescence microscopy of hearts from BMT group revealed that expressions of HSP32 and HSP70 were promoted within cardiomyocytes in the infarction zone and the peri-infarct zone, and expressed within some transplanted bone marrow cells as well. RT-PCR also showed the mRNA expression levels of HSP32 and HSP70 in BMT group were significantly higher than those of the control group, peaked on day 3 post-infarct (5.0-fold and 2.9-fold, respectively, P < 0.01), and then gradually reduced. On day 7 post-infarct, cardiac function (EF and FS) was improved, more than that of the control group (14% and 22%, P < 0.05). On day 14 post-infarct, the specific markers for myocardium or vascular endothelial cells were detected in the transplanted bone marrow cells. The cardiac function was further improved in the BMT group (P < 0.01)., Conclusion: At the early phase after BMT, the expressions of HSP32 and HSP70 were upregulated in both transplanted cells and recipient endogenous cardiomyocytes, which improved the acute ischemic cardiac function.

Objective: To investigate the possible mechanisms of improving ischemic myocardial function by transplantation of bone marrow cells in a rat ischemic heart model., Methods: Myocardial infarction was induced in inbred Lewis rats by left anterior descending artery ligation. Bone marrow cells were injected into an ischemic zone (BMI group). On days 1, 3, 7, 14 and 28 post-transplantation, the expressions of vascular endothelial growth factor (VEGF) and its receptor (Flk-1) and the differentiation of transplanted cells were determined by immunofluorescence and RT-PCR. The number of vessels was examined by immunohistochemistry. The cardiac function was evaluated by hemodynamics., Results: Immunofluorescence microscopy of hearts from BMI group revealed that expressions of VEGF and Flk-1 were promoted within cardiomyocytes in the infarction zone, the peri-infarct zone and in some transplanted bone marrow cells. RT-PCR also showed that mRNA expression levels of VEGF and Flk-1 in BMI group were significantly higher than those of the control group, reached the highest level on days 3 and 14 post-transplantation, and then gradually declined. On days 7, 14 and 28, the vessel count showed the number of blood vessels in the BMI group was greater than that of the control group at the same time, and the cardiac function in the BMI group was improved more significantly than that of the control group. After day 14, the specific markers for myocardium or vascular endothelial cells were detected in the transplanted bone marrow cells., Conclusions: BMI improved the acute ischemic cardiac function by both upregulating the expressions of VEGF and Flk-1 in transplanted BMCs and recipient endogenous cardiomyocytes that enhanced angiogenesis.