Background Diabetes mellitus could cause numerous complications and health problems including abnormality of endochondral bone formation during embryogenesis. However, the underlying mechanisms still remain obscure. Methods Streptozotoci (STZ) was injected to induce pregestational diabetes mellitus (PGDM) mouse model. The femurs of E18.5 mouse embryos from control and PGDM groups were harvested. Morphological staining was implemented to determine the abnormality of the bone development. The expressions of the key genes participating in osteogenesis (e.g., Sox9, Runx2, and Osterix), the NF-κB signaling molecules (e.g., P50, P65, IκBα), and the corresponding regulatory factors (e.g., Bmp2, phospho-p38) were evaluated by immunofluorescence, quantitative PCR and western blot. Finally, in vitro chondrocyte differentiation model was employed to verify the role of NF-κB on the expressions of chondro-osteogenic markers. Results Alcian blue/alizarin red double staining and H&E staining demonstrated the restriction of skeletal development and relatively extended hypertrophic zone at growth plate in E18.5 STZ-induced diabetic mouse embryos compared to the control. Immunofluorescent staining and qPCR showed that Sox9 expression increased, while Runx2 and Osterix expressions decreased in the growth plate of the offspring of PGDM mice. Immunofluorescence of P65 manifested the activation of NF-κB signaling in growth plate in PGDM mouse embryos. Furthermore, the relatively extended hypertrophic zone was also observed in the growth plate of the NF-κB-activated transgenic mice, as well as the activated p65 up-regulated the expression of Bmp2 and p-p38. In ATDC5 cells, we could observe the high glucose up-regulated the P50 and P65 expressions and down-regulated IκBα expression, but the high glucose-activated NF-κB signaling could be reversed by addition of Bay (inhibitor of NF-κB signaling). The expression changes of Bmp2, Sox9 and Runx2 in presence of high glucose were resumed too. Conclusion Our data revealed that NF-κB signaling was involved in mediation effects of dysfunctional trans-differentiation of hypertrophic chondrocytes in the embryonic growth plate induced by maternal diabetic mellitus.
IntroductionTo investigate the effect of exercise on the walking economy (WE) of patients with chronic neurological conditions (CNCs) and to determine the type of physical activity that best improves the WE of patients with CNCs.MethodsFour electronic databases were searched until December 2022 (Web of Science, PubMed, Cochrane, and CINAHL). Studies were screened using the following inclusion criteria: 1. randomized controlled or non-randomized controlled trials; 2. exercise interventions >4 weeks in duration; 3. patients aged ≥18 years with a diagnosis of CNCs. 4. walking economy of patients measured before and after the intervention. The PEDro scale was used to assess the methodological quality of the included studies.Results and discussionTwenty-two studies met the inclusion criteria. Meta-analysis results showed that exercise significantly improved WE (g = −0.352, 95% CI, −0.625 to −0.078, P = 0.012). Subgroup analysis revealed that patients who received exercise showed better WE compared with those who underwent no control intervention (g = −0.474, 95% CI, −0.636 to −0.311, P < 0.001). However, exercise therapy did not show a significant improvement of WE compared with control groups (g = −0.192, 95% CI, −0.451 to 0.067, P = 0.146). In addition, we found that endurance combined with resistance, high-intensity intermittent, and other training modalities resulted in better WE compared with the pre-intervention. Of these, interval training has the greatest effect on improving WE. In conclusion, exercise can improve WE in patients with CNCs. More randomized controlled trials are necessary for the future.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022361455, identifier: CRD42022361455.
BackgroundWhile emerging studies have suggested an association of cardiorespiratory fitness (CRF) with stroke risk and overall health outcomes, little is known regarding the optimum methods of CRF measurement in patients with mild acute ischemic stroke.ObjectiveThe aim of this study was to explore the association between the 6-min walk distance (6MWD) and other measurements related to CRF in patients with mild ischemic stroke at the acute stage.MethodsA total of 30 patients with stroke and 71 healthy subjects matched for age and grip strength (GS) were prospectively recruited. All patients were within 14 days after stroke onset and presented mild motor impairment (with a full score of Fugl-Meyer Motor Assessment). Demographic data of both groups and clinical information of the stroke group were documented, and the CRF comparison between the two groups was conducted. Each participant underwent a one-time assessment of 6MWD and a series of measurements related to CRF, including GS, 10-m walk test (10mWT), five-times sit-to-stand time (FTSST), functional reaching test (FRT), Berg Balance Scale (BBS), and waistline. Pearson's product-moment correlation coefficient test and multiple linear regression were performed to explore the indicators of CRF.ResultsSignificant moderate correlations (0.3 < r <0.6) were found between 6MWD and GS of left hand (GS-left) (r = 0.573, p = 0.001), GS of right hand (GS-right) (r = 0.524, p = 0.003), FTSST (r = −0.551, p = 0.002), 10mWT (r = 0.554, p = 0.001), and FRT (r = 0.449, p = 0.021) in the patient group. While 6MWD displayed significant moderate correlations with waistline (r = 0.364, p = 0.002), 10mWT (r = 0.512, p < 0.001), FTSST (r = −0.573, p < 0.001), and FRT (r = 0.550, p < 0.001) in the healthy group. All these dependent variables were entered into a stepwise multiple linear regression analysis to evaluate their values in estimating CRF as measured by 6MWD in each group. Analyses suggested that GS-left (p = 0.002) and FTSST (p = 0.003) were the indicators of CRF in the patient group with stroke and explained 51.4% of the variance of 6MWD (R2 = 0.514); FTSST (p < 0.001), 10mWT (p < 0.001), and FRT (p = 0.021) were the indicators of CRF in the healthy group and explained 58.9% of variance of 6MWD (R2 = 0.589).ConclusionsOur data confirmed that CRF is impaired in patients with mild ischemic stroke at the acute phase. Moreover, GS-left may be an optional indicator of CRF in patients with mild acute ischemic stroke, but not in healthy people.Clinical Trial Registrationwww.chictr.org.cn, identifier: ChiCTR2000031379.
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