Trimanganese Tetroxide Nanozyme protects Cartilage against Degeneration by Reducing Oxidative Stress in Osteoarthritis.

Osteoarthritis, a chronic degenerative cartilage disease, is the leading cause of movement disorders among humans. Although the specific pathogenesis and associated mechanisms remain unclear, oxidative stress-induced metabolic imbalance in chondrocytes plays a crucial role in the occurrence and development of osteoarthritis. In this study, a trimanganese tetroxide (Mn3 O4 ) nanozyme with superoxide dismutase (SOD)-like and catalase (CAT)-like activities is designed to reduce oxidative stress-induced damage and its therapeutic effect is investigated. In vitro, Mn3 O4 nanozymes are confirmed to reprogram both the imbalance of metabolism in chondrocytes and the uncontrolled inflammatory response stimulated by hydrogen peroxide. In vivo, a cross-linked chondroitin sulfate (CS) hydrogel is designed as a substrate for Mn3 O4 nanozymes to treat osteoarthritis in mouse models. As a result, even in the early stage of OA (4 weeks), the therapeutic effect of the Mn3 O4 @CS hydrogel is observed in both cartilage metabolism and inflammation. Moreover, the Mn3 O4 @CS hydrogel maintained its therapeutic effects for at least 7 days, thus revealing a broad scope for future clinical applications. In conclusion, these results suggest that the Mn3 O4 @CS hydrogel is a potentially effective therapeutic treatment for osteoarthritis, and a novel therapeutic strategy for osteoarthritis based on nanozymes is proposed.

Amelioration of chronic prostatitis by fractions of Mongolian medicine Hosta plantaginea flowers via inhibition of NF-κB, MAPKs, JAK-STAT, and PI3K-Akt signaling pathways in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Hosta plantaginea (Lam.) Aschers flower is an important Mongolian medicine beneficial in the treatment of chronic prostatitis (CP) in the absence of scientific evidence. AIM OF THE STUDY: The aim of this study was to reveal the therapeutical effects and potential mechanisms of H. plantaginea flowers extract (HP) and its different polarity fractions (HPA∼D) on autoimmune CP (ACP) model rats. MATERIALS AND METHODS: Sprague-Dawley male rats were randomly assigned to 13 groups (n = 6/group). Except the sham group, all rats were injected with a mixture of prostate antigen and complete Freund's adjuvant on days 0, 7, and 21 to establish ACP model rats. Afterwards, ACP model rats were orally gavaged with HP or HPA∼D (1 and 4 g/kg of raw herbal material) or positive drug (Prostat, 200 mg/kg) daily from day 21 to day 50 for 30 days, while the sham and model groups were treated simultaneously with isopyknic of 0.3% sodium carboxymethyl cellulose. Histopathological analysis, biochemical parameters, and protein expression of prostate tissues were investigated. RESULTS: In comparison with the model group, all fraction groups experienced improved CP effects, including restored body weight, reduced prostate gland edema and prostate index, decreased prostatic leukocytes, increased prostatic lecithin bodies, and alleviated histopathological damage to prostate tissue. Furthermore, all fraction groups markedly inhibited the phosphorylated protein of nuclear factor kappa-B p65 (NF-κB p65), NF-κB inhibitor alpha (IκBα), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (Erk), just another kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt) than the model group. CONCLUSION: All fractions of HP exerted significant anti-CP effects by inhibiting NF-κB, MAPKs, JAK-STAT and PI3K-Akt pathways in ACP model rats. These findings provide scientific evidence that H. plantaginea flowers can be used as a pivotal Mongolian medicine in clinical applications for the treatment of CP.

Efficacy of the No. 10 lymphadenectomy with spleen preservation on patients with gastric cancer and/or esophagogastric junction adenocarcinoma who underwent total gastrectomy: a systematic review and meta-analysis.

Background: Surgery with total gastrectomy and D2 lymph node dissection (LND) has been recommended as the standard treatment for patients with advanced upper and middle gastric carcinoma and/or Siewert type II/III adenocarcinoma of the esophagogastric junction (AEG). However, whether the No. 10 lymph node (No. 10 LN, also known as splenic hilar LN) should be dissected in total gastrectomy remains controversial. We aimed to evaluate whether the No. 10 LND with spleen preservation has survival benefit for patients with gastric cancer and/or AEG who underwent the total gastrectomy. Methods: The PubMed, Embase, the Cochrane Library, ClinicalTrials.gov and American Society of Clinical Oncology.org (ASCO.org) were electronically searched to identify eligible studies. The primary outcome was the survival rate, and secondary outcomes included the disease-free survival (DFS) rate and side effects. The Review Manager 5.3.5 software was used for the meta-analysis. The odds ratio (OR) and mean difference with 95% confidence interval (CI) were calculated. The statistical heterogeneity was assessed using chi-square (χ2) and I2 tests. Results: Eight studies enrolling a total of 4,131 patients were eligible for our review. The meta-analysis results demonstrated that the No. 10 LND group was significantly better than the non-No. 10 LND group in terms of the 3- (OR =0.71, 95% CI: 0.62-0.81, P<0.00001) and the 5-year (OR =0.66, 95% CI: 0.58-0.75, P<0.00001) survival rates but not in the 1-year survival rate (OR =0.91, 95% CI: 0.75-1.11, P=0.36). The DFS rates in the No. 10 LND group were significantly increased after 1 (OR =0.76, 95% CI: 0.61-0.93, P=0.008), 3 (OR =0.69, 95% CI: 0.60-0.81, P<0.00001), and 5 (OR =0.66, 95% CI: 0.56-0.76, P<0.00001) years compared with those in the non-No. 10 LND group. Discussion: Evidence shows that the No. 10 LND with spleen preservation can improve the survival and the DFS rates for patients with gastric cancer and/or Siewert type II/III AEG who underwent the total gastrectomy. High-quality prospective trials are expected.

Nootkatone protects cartilage against degeneration in mice by inhibiting NF-κB signaling pathway.

Osteoarthritis is a common chronic disease associated with chondrocyte inflammation and cartilage matrix hydrolyzation. Studies report that IL-1ß plays a critical role in osteoarthritis. Anti-inflammatory effect of nootkatone has been explored in acute and chronic inflammatory disease, thus the current study sought to explore its therapeutic effect in osteoarthritis. Notably, the effect of nootkatone in osteoarthritis has not been elucidated. Therefore, murine primary chondrocytes were extracted and ACLT induced OA mouse model was established in the current study to explore the therapeutic effect of nootkatone in OA both in vitro and in vivo. The findings showed that nootkatone inhibited inflammatory response and protected cartilage balance in murine primary chondrocyte. Further analysis showed that nootkatone suppressed inflammation and protected cartilage against degeneration induced by ACLT surgery in mice. The cellular mechanism of the protective effect of nootkatone in osteoarthritis and associated signaling pathway was identified as the NF-κB signaling pathway. In summary, the findings of the current study indicated that nootkatone is a potential therapeutic agent for OA.

Successful Experience of Laparoscopic Pancreaticoduodenectomy and Digestive Tract Reconstruction With Minimized Complications Rate by 14 Case Reports.

Laparoscopic pancreatic surgery is one of the most sophisticated and advanced applications of laparoscopy in the current surgical practice. The adoption of laparoscopic pancreaticoduodenectomy (LPD) has been relatively slow due to the technical challenges. The aim of this study is to review and characterize our successful LPD experiences in patients with distal bile duct carcinoma, periampullary adenocarcinoma, pancreas head cancer, and duodenal cancer and evaluate the clinical outcomes of LPD for its potential in oncologic surgery applications.We retrospectively analyzed the clinical data from 14 patients who underwent LPD from August 2013 to February 2015 in our institute.We presented our LPD experience with no cases converted to open surgery in all 14 cases, which included 10 cases of laparoscopic digestive tract reconstruction and 4 cases of open digestive tract reconstructions. There were no deaths during the perioperative period and no case of gastric emptying disorder or postoperative bleeding. The other clinical indexes were comparable to or better than open surgery.Based on our experience, LPD could be potentially safe and feasible for the treatment of early pancreas head cancer, distal bile duct carcinoma, periampullary adenocarcinoma, and duodenal cancer. The master of LPD procedure requires technical expertise but it can be accomplished with a short learning curve.