MicroRNA-99a regulates early chondrogenic differentiation of rat mesenchymal stem cells by targeting the BMPR2 gene.

Mesenchymal stem cells (MSCs) are candidates for the regeneration of articular cartilage as they possess the potential for chondrogenic differentiation. MSCs are easily obtained and expanded in vitro. Specific microRNAs (miRNAs) that regulate chondrogenesis have yet to be identified and the mechanisms involved remain to be defined. The miRNAs regulate biological processes by binding target mRNA to reduce protein synthesis. In this study, we show that expression of miR-99a and miR-125b-3p were increased during early chondrogenic differentiation of MSCs (rMSCs) derived from the Norwegian brown rat (Rattus norvegicus). MiR-99a knockdown promoted proteoglycan deposition and increased the expression of ACAN and COL2A1 during early chondrogenic differentiation. MiR-99a knockdown promoted early chondrogenic differentiation of rMSCs. A dual-luciferase reporter gene assay showed that miR-99a targeted a putative binding site in the 3'-UTR of bone morphogenetic protein (BMP) receptor type 2 (BMPR2). Overexpression of miR-99a reduced the expression levels of BMPR2 protein. The expression of total p38 and p-p38 increased at 7 and 14 days during early chondrogenic differentiation of rMSCs. Reduction in levels of total p38 and p-p38 protein followed miR-99a overexpression during early chondrogenic differentiation of rMSCs. BMPR2 silencing reversed the effects of miR-99a inhibition on proteoglycan deposition and protein expression of ACAN, COL2A1, total p38 and p-p38 during early chondrogenic differentiation of rMSCs. In conclusion, the findings of these in vitro studies in rat MSCs support a role for miR-99a as a negative regulator of early chondrogenic differentiation by directly targeting the BMPR2 gene at an early stage.

Do stress fractures induce hypertrophy of the grafted fibula? A report of three cases received free vascularized fibular graft treatment for tibial defects.

The presence of large segmental defects of the diaphyseal bone is challenging for orthopedic surgeons. Free vascularized fibular grafting (FVFG) is considered to be a reliable reconstructive procedure. Stress fractures are a common complication following this surgery, and hypertrophy is the main physiological change of the grafted fibula. The exact mechanism of hypertrophy is not completely known. To the best of our knowledge, no studies have examined the possible relationship between stress fractures and hypertrophy. We herein report three cases of patients underwent FVFG. Two of them developed stress fractures and significant hypertrophy, while the remaining patient developed neither stress fractures nor significant hypertrophy. This phenomenon indicates that a relationship may exist between stress fractures and hypertrophy of the grafted fibula, specifically, that the presence of a stress fracture may initiate the process of hypertrophy.

The association between coffee consumption and risk of incident depression and anxiety: Exploring the benefits of moderate intake.

Accumulating evidence has reported the associations of coffee consumption with physical conditions and mortality, but the associations with mental disorders were limited. The objective of this study was to examine the associations of coffee consumption with incident depression and anxiety, and to assess whether the associations differed by coffee subtypes (instant, ground, and decaffeinated coffee) or additives (milk, sugar-sweetened, and artificial-sweetened). In this prospective cohort study, we utilized data from the UK Biobank and included a total of 146,566 participants who completed the touchscreen questionnaire at baseline between 2006 and 2010. During the follow-up, incident depression and anxiety were measured in 2016 using the Patient Health Questionnaire (PHQ)-9 and the Generalised Anxiety Disorder Assessment (GAD)-7, respectively. Multivariable-adjusted logistic regression models and restricted cubic splines were used to assess the associations. Approximately 80.7% of participants reported consuming coffee, and most drank 2 to 3 cups per day (41.2%). We found J-shaped associations between coffee consumption and both incident depression and anxiety, with the lowest risk of the mental disorders occurring at around 2-3 cups per day. Results were similar for participants who drank 2-3 cups of ground coffee, milk-coffee, or unsweetened coffee. Our findings highlight that 2-3 cups of coffee consumption could be recommended as part of a healthy lifestyle to improve mental health.

Extract of Stellera Chamaejasme L. Inhibits the Progression of Hepatocellular Carcinoma by Regulating miR-134-5p and JAK1/STAT3 Pathway.

Background: Hepatocellular carcinoma (HCC) poses a growing threat to humans due to poor prognosis. Extract of stellera chamaejasme L. (ESC) is reported to inhibit metastasis of HCC. However, the underlying mechanism of ESC in regulating the progression of HCC needs to be further investigated. Methods: 3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to measure cell proliferation. Flow cytometry was employed to check cell apoptosis. Transwell assay was conducted to assess the abilities of cell migration and invasion. The protein levels of proliferating cell nuclear antigen, cleaved caspase 3 (c-caspase 3), E-cadherin, janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), and phosphorylated STAT3 were detected by Western blot. The interaction between miR-134-5p and JAK1 was predicted by starBase, which was verified by the dual-luciferase reporter assay and RNA pull-down assay. The messenger RNA levels of miR-134-5p and JAK1 were determined by quantitative real-time polymerase chain reaction. Results: The results showed that the higher concentration or the longer time treatment of ESC led to the lower survival rate of HCC cells. Besides, ESC induced apoptosis and impeded migration and invasion of HCC cells. Moreover, downregulation of miR-134-5p inverted the effects of ESC-mediated repression on HCC progression. Further studies indicated that miR-134-5p targeted the 3'-untranslated region (3'UTR) of JAK1 and reversed JAK1-mediated impacts on HCC progression. Simultaneously, ESC inactivated JAK1/STAT3 pathway by regulating the expression of miR-134-5p. Conclusion: ESC suppressed HCC progression by upregulating the expression of miR-134-5p and blocking JAK1/STAT3 pathway.

Three dimensional finite element analysis of the influence of posterior tibial slope on the anterior cruciate ligament and knee joint forward stability.

OBJECTIVE: To explore the biomechanical influence of posterior tibial angle on the anterior cruciate ligament and knee joint forward stability. METHODS: The left knee joint of a healthy volunteer was scanned by CT and MRI. The data were imported into Mimics software to obtain 3D models of bone, cartilage, meniscus and ligament structures, and then Geomagic software was used to modify of the image. The relative displacement between tibia and femur and the stress of ACL were recorded. RESULTS: ACL tension was 12.195 N in model with 2∘ PTS, 12.639 N in model with 7∘ PTS, 18.658 N in model with 12∘ PTS. the relative displacement of the tibia and femur was 2.735 mm in model with 2∘ PTS, 3.086 mm in model with 7∘ PTS, 3.881 mm in model with 12∘ PTS. In the model with 30∘ flexion, the maximum tension of ACL was 24.585 N in model with 2∘ PTS, 25.612 N in model with 7∘ PTS, 31.481 N in model with 12∘ PTS. The relative displacement of the tibia and femur was 5.590 mm in model with 2∘ PTS, 6.721 mm in model with 7∘ PTS, 6.952 mm in model with 12∘ PTS. In the 90∘ flexion models, ACL tension was 5.119 N in model with 2∘ PTS, 8.674 N in model with 7∘ PTS, 9.314 N in model with 12∘ PTS. The relative displacement of the tibia and femur was 0.276 mm in model with 2∘ PTS, 0.577 mm in model with 7∘ PTS, 0.602 mm in model with 12∘ PTS. CONCLUSION: The steeper PTS may be a risk factor in ACL injury.

Psoralen stimulates osteoblast proliferation through the activation of nuclear factor-κB-mitogen-activated protein kinase signaling.

Osteoporosis is a systemic skeletal disease that leads to increased bone fragility and susceptibility to fracture. Approximately 50% of postmenopausal women develop osteoporosis as a result of postmenopausal estrogen deficiency. To reduce fractures related to osteoporosis in women, previous studies have focused on therapeutic strategies that aim to increase bone formation or decrease bone resorption. However, pharmacological agents that aim to improve bone fracture susceptibility exhibit side effects. Current studies are investigating natural alternatives that possess the benefits of selective estrogen receptor modulators (SERMs) without the adverse effects. Recent studies have indicated that phytoestrogen may be an ideal natural SERM for the treatment of osteoporosis. In Chinese herbal medicine, psoralen, as the predominant substance of Psoralea corylifolia, is considered to be a phytoestrogen and is used as a remedy for osteoporosis. A number of studies have demonstrated the efficacy of psoralen in bone formation. However, the pathways and underlying molecular mechanisms that participate in psoralen-induced osteoblast formation are not well understood. In the present study, hFOB1.19 cells were treated with psoralen at different concentrations (0, 5, 10, 15 and 20 µM) for 0, 24, 36, 48 and 72 h, respectively. Reverse transcription-quantitative polymerase chain reaction and western blot assays were performed to detect glucose transporter 3 (GLUT3) expression. A cell counting kit-8 assay was used to analyze cell proliferation. In addition the effects of mitogen activated protein kinase inhibitors on extracellular signal-regulated kinase (ERK), phosphorylated (p)-ERK, p38, p-p38, c-Jun N-terminal kinase (JNK) and p-JNK expressions and cell proliferation were measured, as was the effect of nuclear factor (NF)-κB inhibitor on P65 and GLUT3 expressions and cell proliferation. The results indicated that psoralen stimulates hFOB1.19 cell proliferation in a dose-dependent manner (P<0.05). Phospho-ERK, p38 and JNK were markedly increased by psoralen compared with the control group (P<0.05), and the specific inhibitors of ERK (SCH772984), p38 (SB203580) and JNK (SP600125) reversed the stimulatory effects of psoralen on signal marker phosphorylation (P<0.05). The rate of psoralen-induced cell proliferation was significantly suppressed by inhibitors of ERK, JNK and p38 compared with psoralen treatment alone (P<0.05). In addition, psoralen stimulated osteoblast proliferation via the NF-κB signaling pathway. Therefore, the present findings suggest that psoralen may be a potential natural alternative to SERMs in the treatment of osteoporosis and fractures.

The effect of cupping therapy for low back pain: A meta-analysis based on existing randomized controlled trials.

BACKGROUND: LBP is one of the most common symptoms with high prevalence throughout the world. Conflicting conclusions exist in RCTs on cupping for LBP. OBJECTIVE: To assess the effects and safety of cupping for the patients with LBP. METHODS: Pubmed, Cochrane Library databases, and Embase database were electronically researched. RCTs reporting the cupping for the patients with LBP were included. The meta-analysis was conducted using Review Manager software (version 5.3, Nordic Cochrane Centre). The primary outcome was VAS scores. The secondary outcomes included ODI scores, MPPI scores and complications. RESULTS: Six RCTs were included in this synthesized analysis. The results showed that cupping therapy was superior to the control management with respect to VAS scores (SMD: -0.73, [95% CI: -1.42 to -0.04]; P= 0.04), and ODI scores (SMD: -3.64, [95% CI: -5.85 to -1.42]; P= 0.001). There was no statistical significant difference as regard to MPPI scores. No serious adverse event was reported in the included studies. CONCLUSIONS: Cupping therapy can significantly decrease the VAS scores and ODI scores for patients with LBP compared to the control management. High heterogeneity and risk of bias existing in studies limit the authenticity of the findings.