Ginsenoside Rc alleviates osteoporosis by the TGF-ß/Smad signaling pathway.

Osteoporosis is a common chronic bone disorder in postmenopausal women. Ginsenosides are primary active components in ginseng and the effects of various ginsenoside variants in osteoporosis treatment have been widely revealed. We planned to explore the impact of ginsenoside Rc on bone resorption in an osteoporosis rat model. We used ovariectomized rats to assess the potential impact of ginsenoside Rc on osteoporosis. µ-CT was implemented for analyzing the microstructure of the distal left femur in rats. H&E staining together with Masson staining were applied for bone histomorphometry evaluation. ELISA kits were implemented to detect serum concentrations of TRACP-5b, OCN, CTX, as well as PINP. Ginsenoside Rc treatment lessened the serum levels of TRACP-5b as well as CTX, while increasing serum levels of OCN, and PINP of OVX rats. Moreover, we found that ginsenoside Rc contributed to the synthesis of type I collagen via increasing Col1a1 and Col1a2 levels in femur tissues of ovariectomized rats. Our findings also revealed that ginsenoside Rc activated the TGF-ß/Smad pathway by increasing TGF-ß as well as phosphorylated Smad2/3 protein levels. Ginsenoside Rc alleviates osteoporosis in rats through promoting the TGF-ß/Smad pathway.

Associations between type 2 diabetes mellitus and chronic liver diseases: evidence from a Mendelian randomization study in Europeans and East Asians.

Objective: Multiple observational studies have demonstrated an association between type 2 diabetes mellitus (T2DM) and chronic liver diseases (CLDs). However, the causality of T2DM on CLDs remained unknown in various ethnic groups. Methods: We obtained instrumental variables for T2DM and conducted a two-sample mendelian randomization (MR) study to examine the causal effect on nonalcoholic fatty liver disease (NAFLD), hepatocellular carcinoma (HCC), viral hepatitis, hepatitis B virus (HBV) infection, and hepatitis C virus (HCV) infection risk in Europeans and East Asians. The primary analysis utilized the inverse variance weighting (IVW) technique to evaluate the causal relationship between T2DM and CLDs. In addition, we conducted a series of rigorous analyses to bolster the reliability of our MR results. Results: In Europeans, we found that genetic liability to T2DM has been linked with increased risk of NAFLD (IVW : OR =1.3654, 95% confidence interval [CI], 1.2250-1.5219, p=1.85e-8), viral hepatitis (IVW : OR =1.1173, 95%CI, 1.0271-1.2154, p=0.0098), and a suggestive positive association between T2DM and HCC (IVW : OR=1.2671, 95%CI, 1.0471-1.5333, p=0.0150), HBV (IVW : OR=1.1908, 95% CI, 1.0368-1.3677, p=0.0134). No causal association between T2DM and HCV was discovered. Among East Asians, however, there was a significant inverse association between T2DM and the proxies of NAFLD (ALT: IVW OR=0.9752, 95%CI 0.9597-0.9909, p=0.0021; AST: IVW OR=0.9673, 95%CI, 0.9528-0.9821, p=1.67e-5), and HCV (IVW: OR=0.9289, 95%CI, 0.8852-0.9747, p=0.0027). Notably, no causal association was found between T2DM and HCC, viral hepatitis, or HBV. Conclusion: Our MR analysis revealed varying causal associations between T2DM and CLDs in East Asians and Europeans. Further research is required to investigate the potential mechanisms in various ethnic groups, which could yield new insights into early screening and prevention strategies for CLDs in T2DM patients.

The analgesic effect and safety of preoperative versus postoperative administration of celecoxib in patients who underwent arthroscopic rotator cuff repair: a randomized, controlled study.

AIMS: Celecoxib presents a good analgesic effect in patients who undergo arthroscopic rotator cuff repair (ARCR) surgery, while few studies investigate the optimal timing of celecoxib administration. This study aimed to explore the analgesic effect of preoperative versus postoperative administration of celecoxib in ARCR-treated patients. METHODS: A total of 106 ARCR-treated patients were enrolled and randomized at a 1:1 ratio into preoperative analgesia group (N = 53) and postoperative analgesia group (N = 53). The pain visual analog scale (VAS) score at rest or flexion, salvage consumption of pethidine, patient's satisfaction score, modified University of California at Los Angeles (UCLA) score and adverse events were evaluated. RESULTS: Pain VAS scores at rest at 12 h and D1 (but not D2, D3 or D7) and pain VAS scores at flexion at 12 h, D1 and D2 (but not D3 or D7) were decreased in preoperative analgesia group compared to postoperative analgesia group. Meanwhile, rescue analgesia rate and 7-day pethidine consumption in preoperative analgesia group were lower than that in postoperative analgesia group. Besides, the overall satisfaction scores at D1 and D3 (but not at D7 or M3) were elevated in preoperative analgesia group compared to postoperative analgesia group. However, no difference of modified UCLA scores at D7 or M3, or the occurrences of adverse events were found between the two groups. CONCLUSIONS: Celecoxib preoperative administration remits acute pain and facilitates satisfaction but does not improve long-term shoulder joint function recovery compared to its postoperative administration in patients who undergo ARCR surgery.

Long non-coding RNA NEAT1 and its targets (microRNA-21 and microRNA-125a) in rheumatoid arthritis: Altered expression and potential to monitor disease activity and treatment outcome.

BACKGROUND: The present study aimed to explore the association of long non-coding RNA nuclear-enriched abundant transcript 1 (lnc-NEAT1) with inflammation, disease activity, treatment outcome, and its targets (microRNA [miR]-21 and miR-125a) in patients with rheumatoid arthritis (RA). METHODS: Peripheral blood mononuclear cells were sampled from 130 RA patients at baseline, week (W) 6, and W12, as well as from 60 healthy controls (HCs) after enrollment. Meanwhile, the expressions of lnc-NEAT1, miR-21, and miR-125a were detected by reverse transcription-quantitative polymerase chain reaction. RESULTS: lnc-NEAT1 was elevated, but miR-21 and miR-125a were declined in RA patients compared with HCs (all p < 0.001); meanwhile, lnc-NEAT1 was negatively correlated with miR-21 and miR-125a (both p < 0.05) in RA patients. Besides, elevated lnc-NEAT1 but declined miR-21 and miR-125a were correlated with erythrocyte sedimentation rate (ESR) and C-reactive protein and the 28-joint Disease Activity-ESR score (all p < 0.05) in RA patients. Moreover, lnc-NEAT1 was declined from baseline to W12 in RA patients (p < 0.001). Additionally, lnc-NEAT1 at W12 was declined in response patients compared with non-response patients (p = 0.006), and also decreased in remission patients compared with non-remission patients (p < 0.001). CONCLUSION: lnc-NEAT1 and its targets (miR-21 and miR-125a) correlate with RA risk and disease activity, and declined lnc-NEAT1 associates with better treatment outcome to some extent in RA patients, suggesting that lnc-NEAT1 might be a potential biomarker to monitor disease activity and treatment outcome in RA.

Comparison of analgesic effect, knee joint function recovery, and safety profiles between pre-operative and post-operative administrations of meloxicam in knee osteoarthritis patients who underwent total knee arthroplasty.

AIMS: This study aimed to compare the efficacy and safety of pre-operative and post-operative meloxicam administration regarding post-operative pain control and knee joint function recovery in knee osteoarthritis (KOA) patients who underwent total knee arthroplasty (TKA). METHODS: Totally, 196 KOA patients who underwent TKA were consecutively enrolled and randomly assigned into pre-operative (N = 98) and post-operative administration group (N = 98) as 1:1 ratio. Pre-operative administration group received meloxicam 15 mg at 24 h pre-operation and 7.5 mg at 4 h, 24 h, 48 h, and 72 h post-operation, respectively. Post-operative administration group received meloxicam 15 mg at 4 h post-operation and 7.5 mg at 24 h, 48 h, and 72 h post-operation, respectively. Pain visual analog scale (VAS) at rest and at flexion, patient's global assessment (PGA), patient-controlled analgesia (PCA) consumption, hospital for special surgery (HSS), knee score, and adverse events were assessed. RESULTS: Pre-operative meloxicam administration attenuated pain VAS score at rest at 6 h, 12 h, and 24 h; and pain VAS score at flexion at 6 h, 12 h, 24 h, and 48 h; as well as PGA score at 6 h, 12 h, 48 h post-TKA compared with post-operative meloxicam administration. Additional and total consumption of PCA were both decreased in pre-operative meloxicam administration group than post-operative meloxicam administration group, while HSS knee score at 3 months post-TKA was similar between pre-operative and post-operative meloxicam administration groups. Regarding safety, the incidence of adverse events was of no difference between the two groups. CONCLUSION: Pre-operative administration of meloxicam might assist the post-operative pain management and care in KOA patients who underwent TKA.

Preventive Effects of Evodiamine on Dexamethasone-Induced Osteoporosis in Zebrafish.

The aim of this study was to investigate the effect of evodiamine (EV) on dexamethasone-induced osteoporosis in zebrafish. Zebrafish larvae were exposed to different concentrations of dexamethasone to obtain the osteoporosis in zebrafish. Calcium, phosphorus, and alizarin red staining determination were performed to evaluate the effects of EV on bone mineralization. Alkaline phosphatase (ALP), hydroxyproline (HP), and tartrate resistant acid phosphatase (TRAP) were also measured by commercial kits. The expression of MMP3-OPN-MAPK pathway in zebrafish was measured by Western blot. RT-PCR was used to determine mRNA levels of MMP3, OPN, and MAPK. EV could significantly increase the content of calcium and phosphorus. The results of alizarin red staining showed that EV could significantly increase the calcium sink of horse fish, increasing the area of bone formation. EV could increase the content of hydroxyproline in zebrafish. EV also increased ALP and TRAP in zebrafish. Western blot and RT-PCR results showed that EV restored the MMP3-OPN-MAPK pathway in zebrafish. In conclusion, we found that EV can alleviate dexamethasone-induced osteoporosis in zebrafish. The mechanism is related to activating MMP3-OPN-MAPK pathway and then activating bone remodeling.

Zuogui Pill improves the dexamethasone-induced osteoporosis progression in zebrafish larvae.

The current study was to evaluate the protective effects of Chinese medicine prescription Zuogui Pill (ZGP) on osteoporosis (OP) in zebrafish larvae induced by dexamethasone. Alizarin Red staining, calcium and phosphorus determination were performed to evaluate the effect of ZGP on bone mineralization. Hydroxyproline (HP), Alkaline phosphatase (ALP), and tartrate resistant acid phosphatase (TRAP) were also measured by commercial kits. We found that ZGP had positive effects in increasing bone mineral content (BMC), strengthening bone biomechanical, promoting bone formation, inhibiting bone resorption, and mediating protein levels of TGF-ß1/Smads signaling pathway. The findings demonstrated that ZGP treatments inhibited the phosphorylation of TGF-ß and p-Smad 3 as well as the expressions of collagen I and collagen II by western blot. Taken together, we demonstrated that ZGP may prevent osteoporosis via reversing the imbalance of bone fomation/bone resorption and activating the TGF-ß-Smad signal.

In vitro enhancement effect of humic acid on the progression of lung cancer cells.

Humic acid, a group of polymer, resulting from the decomposition of organic matter has been implicated as a possible etiological factor for Black foot disease and cancer. However, the role of humic acid in carcinogenesis is not well clarified. In this study, we evaluated the enhancement effect of humic acid on the progression of A549 human lung cancer cells. Our findings showed that humic acid increased the migration, adhesion and invasion of A549 cells significantly after treatment at the concentration of 50 and 100 microg/ml for 24 and 48 h as compared with the untreated group. Results of zymography assay indicated that humic acid enhanced the activity of matrix metalloproteinase 9 (MMP-9). By western blotting analysis, humic acid increased the expression of phosphorylated focal adhesion kinase (FAK) and integrin alpha2 that may mediate cell motility and adhesion. Since the activation of signal pathways such as phosphoinositide 3-kinase/Akt (PI3K/Akt) and mitogen-activated protein kinases (MAPKs) may play a role in the cell invasion, we detected the expression of phosphorylated Akt and phosphorylated MAPKs including extracellular signal-regulated kinase (ERK), Jun N-terminus kinase (JNK), and p38. The result indicated that all kinases stated above were activated by humic acid in A549 cells. However, by adding an inhibitor respectively in the invasion assay, only Akt, ERK, and JNK pathways were found to be involved in the enhancing the invasion of A549 cells by humic acid. In addition, results of electrophoretic mobility shift assay (EMSA) demonstrated that humic acid increased nuclear extract binding to the DNA probe of activator protein 1 (AP-1) and nuclear factor kappaB (NFkappaB) respectively, implying that humic acid enhanced the progression of A549 lung cancer cells through activating multiple signaling pathways including ERK, JNK, and PI3K/Akt and increasing the transcription activation of AP-1 and NFkappaB.