Polyprenylated xanthones with potential anti-inflammatory and anti-HIV effects from the stems and leaves of Cratoxylum cochinchinense (Lour.) Blume.

A phytochemical study on the stems and leaves of Cratoxylum cochinchinense (Lour.) Blume resulted in the isolation and characterisation of a new polyprenylated xanthone, cratocochinone (1), as well as seven known analogues, fuscaxanthone K (2), pruniflorone Q (3), 1,3,5,8-tetrahy-droxy- 2-(3-methybut-2-enyl)-4-(3,7-dimethylocta-2,6-dienyl) xanthone (4), cochinensoxanthone (5), cratoxylum-xanthone B (6), cochinchinone I (7) and cochinchinone K (8). The chemical structure of 1 was determined by comprehensive spectral analyses. The known compounds 2 - 8 were identified by comparing their experimental spectroscopic data with those reported data in the literature. The anti-inflammatory and anti-HIV effects of all isolates 1-8 were evaluated. As a result, compounds 1-8 showed remarkable inhibitory effects against nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells showing IC50 values ranging from 0.68 ± 0.06 to 10.27 ± 0.18 µM. Meanwhile, compounds 1-8 displayed notable anti-HIV-1 reverse transcriptase (RT) effects with EC50 values ranging from 0.19 to 10.72 µM.

A network of acetyl phosphate-dependent modification modulates c-di-AMP homeostasis in Actinobacteria.

Cyclic purine nucleotides are important signal transduction molecules across all domains of life. 3',5'-cyclic di-adenosine monophosphate (c-di-AMP) has roles in both prokaryotes and eukaryotes, while the signals that adjust intracellular c-di-AMP and the molecular machinery enabling a network-wide homeostatic response remain largely unknown. Here, we present evidence for an acetyl phosphate (AcP)-governed network responsible for c-di-AMP homeostasis through two distinct substrates, the diadenylate cyclase DNA integrity scanning protein (DisA) and its newly identified transcriptional repressor, DasR. Correspondingly, we found that AcP-induced acetylation exerts these regulatory actions by disrupting protein multimerization, thus impairing c-di-AMP synthesis via K66 acetylation of DisA. Conversely, the transcriptional inhibition of disA was relieved during DasR acetylation at K78. These findings establish a pivotal physiological role for AcP as a mediator to balance c-di-AMP homeostasis. Further studies revealed that acetylated DisA and DasR undergo conformational changes that play crucial roles in differentiation. Considering the broad distribution of AcP-induced acetylation in response to environmental stress, as well as the high conservation of the identified key sites, we propose that this unique regulation of c-di-AMP homeostasis may constitute a fundamental property of central circuits in Actinobacteria and thus the global control of cellular physiology.IMPORTANCESince the identification of c-di-AMP is required for bacterial growth and cellular physiology, a major challenge is the cell signals and stimuli that feed into the decision-making process of c-di-AMP concentration and how that information is integrated into the regulatory pathways. Using the bacterium Saccharopolyspora erythraea as a model, we established that AcP-dependent acetylation of the diadenylate cyclase DisA and its newly identified transcriptional repressor DasR is involved in coordinating environmental and intracellular signals, which are crucial for c-di-AMP homeostasis. Specifically, DisA acetylated at K66 directly inactivates its diadenylate cyclase activity, hence the production of c-di-AMP, whereas DasR acetylation at K78 leads to increased disA expression and c-di-AMP levels. Thus, AcP represents an essential molecular switch in c-di-AMP maintenance, responding to environmental changes and possibly hampering efficient development. Therefore, AcP-mediated posttranslational processes constitute a network beyond the usual and well-characterized synthetase/hydrolase governing c-di-AMP homeostasis.

Groundwater health risk assessment of North China Plain based on Monte Carlo model sensitivity analysis and morphological analysis: A case study of Shijiazhuang City.

The rapid development of the social economy and the influence of human activities can lead to aggravated groundwater pollution. Groundwater safety is the premise of residents' health. Therefore, studying the sustainable utilization and health risks of groundwater quality is important. The groundwater quality and potential health risks were evaluated in the Shijiazhuang area, which is located in the North China Plain in this paper. Based on 159 groundwater samples collected in the study area, the potential health risks of As, Cr6+, Ni, Pb, F-, and NO3 - to humans were evaluated from oral and skin contact. Results of the human health risk assessment showed that the average carcinogenic risk and non-carcinogenic risk of children are higher than those of adults. According to the spatial distribution of the total risk value, adults and children in the southwest of the study area face higher risks. Because of the uncertainty of USEPA, Monte Carlo simulation was used to calculate the probability of health risk assessment and prioritization of contaminant treatment. The results of the Monte Carlo simulation showed that the acceptable range for children is 6.82%, and the acceptable range for adults is 18.07%. According to the HRWM model, carcinogenic pollutants mainly include As, Cr6+, and Ni. The most important chemical species of As is HAsO4 2-, followed by H2AsO4 -. Similarly, CrO4 2- and Ni2+ are the main forms of Cr6+ and Ni. The results of this study can provide data support for the protection and management of groundwater quality in the North China Plain. PRACTITIONER POINTS: Children are more susceptible to carcinogenic risk than adults. After calculation, the main influencing elements are Ni and Cr. Metal morphology analysis was carried out, and the results showed that HAsO4 2-, CrO4 2-, and Ni2+ were the main types.

Allosteric regulation by c-di-AMP modulates a complete N-acetylglucosamine signaling cascade in Saccharopolyspora erythraea.

c-di-AMP is an essential and widespread nucleotide second messenger in bacterial signaling. For most c-di-AMP synthesizing organisms, c-di-AMP homeostasis and the molecular mechanisms pertaining to its signal transduction are of great concern. Here we show that c-di-AMP binds the N-acetylglucosamine (GlcNAc)-sensing regulator DasR, indicating a direct link between c-di-AMP and GlcNAc signaling. Beyond its foundational role in cell-surface structure, GlcNAc is attractive as a major nutrient and messenger molecule regulating multiple cellular processes from bacteria to humans. We show that increased c-di-AMP levels allosterically activate DasR as a master repressor of GlcNAc utilization, causing the shutdown of the DasR-mediated GlcNAc signaling cascade and leading to a consistent enhancement in the developmental transition and antibiotic production in Saccharopolyspora erythraea. The expression of disA, encoding diadenylate cyclase, is directly repressed by the regulator DasR in response to GlcNAc signaling, thus forming a self-sustaining transcriptional feedback loop for c-di-AMP synthesis. These findings shed light on the allosteric regulation by c-di-AMP, which appears to play a prominent role in global signal integration and c-di-AMP homeostasis in bacteria and is likely widespread in streptomycetes that produce c-di-AMP.

A Comparison of Minimally Invasive Surgical Techniques and Standard Open Discectomy for Lumbar Disc Herniation: A Network Meta-analysis.

BACKGROUND: Lumbar disc herniation is a common spinal disease that causes low back pain; surgery is required when conservative treatment is ineffective. There is a growing demand for minimally invasive surgery in younger patient populations due to their fear of significant damage and a long recovery period following standard open discectomy. The development history of minimally invasive surgery is relatively short, and no gold standard has been established. OBJECTIVES: We aimed to find, via a network meta-analysis, the best treatment for low back pain in younger patient populations. STUDY DESIGN: Network meta-analysis. METHODS: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched. Data quality was evaluated using RevMan 5.3 (The Nordic Cochrane Centre for The Cochrane Collaboration), while STATA 14.0 (StataCorp LLC) was used for the network meta-analysis and to merge data on the Visual Analog Scale (VAS) score, Oswestry Disability Index (ODI) score, complication, blood loss, reoperation rate, and function score. RESULTS: We included 50 randomized controlled trials, involving 7 interventions; heterogeneity and inconsistency were acceptable. Comparatively, microendoscopic discectomy and percutaneous endoscopic lumbar discectomy were the best surgical procedures from the aspects of VAS score and ODI score, while standard open discectomy was the worst one from the aspect of ODI score. Regarding complications, tubular discectomy was preferred with the fewest complications. Additionally, microendoscopic discectomy outperformed other surgical procedures in reducing blood loss and reoperation rate. LIMITATIONS: First, follow-up data were not reported in all included studies, and the follow-up time varied from several months to 8 years, which affected the results accuracy of our study to some extent. Second, there were some nonsurgical factors that also affected the self-reported outcomes, such as rehabilitation and pain management, which also brought a certain bias in our study results. CONCLUSIONS: Compared to standard open discectomy, minimally invasive surgical procedures not only achieve satisfactory efficacy, but also microendoscopic discectomy and percutaneous endoscopic lumbar discectomy can obtain a more satisfactory short-term VAS score and ODI score. Microendoscopic discectomy has significant advantages in blood loss and reoperation rate, and tubular discectomy has fewer postoperative complications.

A novel clinical tool and risk stratification system for predicting the event-free survival of neuroblastoma patients: A TARGET-based study.

Neuroblastoma (NB), considered the most common non-intracranial solid tumor in children, accounts for nearly 8% of pediatric malignancies. This study aimed to develop a simple and practical nomogram to predict event-free survival (EFS) in NB patients and establish a new risk stratification system. In this study, 763 patients primarily diagnosed with NB in the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database were included and randomly assigned to a training set (70%) and a validation set (30%) in a 7:3 ratio. First, the independent prognostic factors of EFS for NB patients were identified through univariate and multivariate Cox regression analyses. Second, a nomogram was created based on these factors and was validated for calibration capability, discriminative, and clinical significance by C-curves, receiver operating characteristic (ROC) curves, and decision curve analysis. Finally, a new risk stratification system was established for NB patients based on the nomogram. The univariate Cox analysis demonstrated that NB patients with age at diagnosis >318 days, International Neuroblastoma Staging System (INSS) stage 4, DNA diploidy, MYCN amplification status, and children oncology group (COG) high-risk group had a relatively poor prognosis. However, according to the multivariate Cox regression analysis, only age, INSS stage, and DNA ploidy were independent predictive factors in NB patients regarding EFS, and a nomogram was created based on these factors. The area under the curve (AUC) values of the ROC curves for the 3-, 5-, and 10-year EFS of this nomogram were 0.681, 0.706, and 0.720, respectively. Additionally, the AUC values of individual independent prognostic factors of EFS were lower than those of the nomogram, suggesting that the developed nomogram had a higher predictive reliability for prognosis. In addition, a new risk stratification system was developed to better stratify NB patients and provide clinical practitioners with a better reference for clinical decision-making. NB patients' EFS could be predicted more accurately and easily through the constructed nomogram and event-occurrence risk stratification system, allowing clinicians to better differentiate NB patients and establish individualized treatment plans to maximize patient benefits.

Construction of a novel clinical nomogram to predict cancer-specific survival in patients with primary malignant adrenal tumors: a large population-based retrospective study.

Background: Primary malignant adrenal tumors were rare and had a poor prognosis. This investigation aimed to create a useful clinical prediction nomogram to anticipate cancer-specific survival (CSS) of patients with a primary malignant adrenal tumor. Method: This study included 1748 patients with malignant adrenal tumor diagnoses subjects from 2000 to 2019. These subjects were allocated randomly into training (70%) and validation (30%) cohorts. Patients with adrenal tumors underwent univariate and multivariate Cox regression analyses to identify the CSS-independent predictive biomarkers. Therefore, a nomogram was created depending on those predictors, and calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA) were used to assess the calibration capacity of the nomogram, discriminative power, and clinical efficiency, respectively. Afterward, a risk system for categorizing patients with adrenal tumors was established. Result: The univariate and multivariate Cox analysis demonstrated the CSS-independent predictive factors, including age, tumor stage, size, histological type, and surgery. As a result, a nomogram was developed using these variables. For the 3-, 5-, and 10-year CSS of this nomogram, the values of the area under the curve (AUC) of the ROC curves were 0.829, 0.827, and 0.822, respectively. Furthermore, the AUC values of the nomogram were higher than those of the individual independent prognostic components of CSS, indicating that the nomogram had stronger prognostic prediction reliability. A novel risk stratification method was created to further improve patient stratification and give clinical professionals a better reference for clinical decision-making. Conclusion: Through the developed nomogram and risk stratification method, the CSS of patients with malignant adrenal tumors could be predicted more precisely, assisting physicians to differentiate patients better and creating personalized treatment strategies to optimize patient benefits.

Anticancer Benefit of Metformin in Patients With Early-Stage Pancreatic Cancer: A Retrospective Cohort Study.

Background: Epidemiologic studies have produced conflicting results on the effects of metformin on pancreatic cancer. This study aimed to observe and analyze whether metformin use is associated with better prognosis in pancreatic cancer. Materials and Methods: In this retrospective cohort study, all baseline data were retrieved from The Chinese Medicine Information Retrieval System (https://dc.wzhospital.cn/vpn/index.html) of The First Affiliated Hospital of Wenzhou Medical University. Survival data were collected by follow-up visits and medical records. Overall survival was the primary endpoint, while progression-free survival and disease-free survival were secondary endpoints. Progression or recurrence was assessed with radiologic images. Results: Seventy-six metformin users and 92 metformin nonusers diagnosed with pancreatic cancer from 2012 to 2020 in this hospital were enrolled. The adjusted hazard ratio for overall survival for metformin users was 0.50 (95% confidence interval = 0.33-0.76), where median overall survival was 16.0 months for metformin users versus 11.5 months for metformin nonusers. The protective effect was also found by analyzing progression-free survival (adjusted hazard ratio = 0.39, 95% confidence interval = 0.18-0.86) and disease-free survival (adjusted hazard ratio = 0.30, 95% confidence interval = 0.14-0.68). In the subgroup analysis, metformin use had a statistically significant association with prolongation of survival in stage I to II pancreatic cancer patients (hazard ratio = 0.47, 95% confidence interval = 0.25-0.91), but not for advanced tumor stage (hazard ratio for IV stage = 0.62, 95% confidence interval = 0.33-1.19), after adjustment for other risk factors. Conclusion: Metformin use is related to favorable survival outcomes of pancreatic cancer, especially in early tumor stage.

Percutaneous endoscopic versus minimally invasive transforaminal lumbar interbody fusion for lumbar degenerative diseases: a meta-analysis.

Introduction: Transforaminal lumbar interbody fusion (TLIF) is commonly used in patients with lumbar degenerative disease (LDD). The most commonly used techniques include minimally invasive TLIF (MIS-TLIF) and percutaneous endoscopic TLIF (PE-TLIF). Aim: To compare the safety and clinical effectiveness of PE-TLIF and MIS-TLIF in treating LDD. Material and methods: We screened for related articles in multiple scientific databases, namely, PubMed, Embase, Cochrane Library, Wanfang, VIP, and CINK, and analyzed the relative outcomes. Results: Based on our inclusion criteria, we selected 8 studies for meta-analysis. There are a total of 229 patients who underwent PE-TLIF and 258 patients who underwent MIS-TLIF. MIS-TLIF and PE-TLIF have similar effectiveness in relieving leg pain and improving the Oswestry Disability Index. However, PE-TLIF is superior in relieving back pain. The pooled data of fusion rates, postoperative analgesic, and complication rates are comparable between the 2 groups. The pooled operation and intra-operative fluoroscopic time are both significantly higher in the PE-TLIF group than the MIS-TLIF group. The pooled intra-operative blood loss, incision length, duration from surgery to ambulation, and hospital stay are significantly lower in the PE-TLIF group than the MIS-TLIF group. Most of the endpoints reveal significant heterogeneity. The endpoints of operation time and intra-operative blood loss reveal significant publication bias. Conclusions: Both PE-TLIF and MIS-TLIF are safe and effective interventions for patients with LDD. When compared, although MIS-TLIF results in reduced operative time, less intra-operative blood loss and enhanced post-operative recovery can be achieved by PE-TLIF.

Lumbar degenerative disease treated by percutaneous endoscopic transforaminal lumbar interbody fusion or minimally invasive surgery-transforaminal lumbar interbody fusion: a case-matched comparative study.

PURPOSE: This study aimed to evaluate the clinical efficacy and imaging results of percutaneous endoscopic transforaminal lumbar interbody fusion (PETLIF) through comparing it with minimally invasive surgery-transforaminal lumbar interbody fusion (MISTLIF). MATERIALS AND METHODS: We performed a retrospective analysis on patients with lumbar degenerative disease treated by PETLIF or MISTLIF from September 2017 to January 2019, and the patients were divided into two groups: the PETLIF group and the MISTLIF group. The clinical and imaging parameters of the two groups were evaluated. RESULTS: There was no significant difference between the two groups in operative time and complication rate. The estimated blood loss and the length of hospital stay in the PETLIF group were significantly better than those in the MISTLIF group. Compared with those before operation, the postoperative VAS-L and VAS-B scores were significantly improved after operation in the both groups. In addition, the postoperative VAS-B score of the PETLIF group was significantly lower than that of the MISTLIF group. At the last follow-up, there was no significant difference between the two groups in the VAS-L score, VAS-B score, ODI score, and bony fusion rate. CONCLUSIONS: Both PETLIF and MISTLIF could achieve satisfactory clinical outcomes in the treatment of lumbar degenerative disease, but our study suggested that PETLIF had less damage, rapid recovery after operation, and short discharge time.

[Effect and Mechanism of Epimedium Polysaccharide on Bone Marrow Hematopoietic Function and Th17/Treg Balance in Aplastic Anemia].

OBJECTIVE: To observe the effects of Epimedium polysaccharides (EPS) on bone marrow hematopoietic function and Th17/Treg balance in aplastic anemia (AA) mice, and preliminarily explore its therapeutic mechanism. METHODS: Forty BALB/C mice were randomly divided into control (control), model (model), stanozolol (stanozolol) and epimedium polysaccharide (EPS) group, with 10 mice in each group. Except for the control group, Acetophenazine, Gy irradiation and cyclophosphamide triple application were used to establish AA models for the other groups. After the model was established, the stanozolol group was intragastrically administered with 4 mg/kg stanozolol suspension, the EPS group was intragastrically administered with 100 mg/kg epimedium polysaccharide, while the control group and the model group were given an equal volume of 0.9% sodium chloride solution by gavage once a day, for 14 consecutive days. The automatic animal blood analyzer was used to detect the changes in peripheral blood hemoglobin (Hb), red blood cells (RBC), white blood cells (WBC) and platelets (PLT), flow cytometry was used to detect the proportion of Treg and Th17 cells, the levels of interleukin 2 (IL-2), interleukin 11 (IL-11) and tumor necrosis factor α (TNF-α) were detected by ELISA, the number of nucleated bone marrow cells was counted, HE staining and immunohistochemical staining were used to detect the number, the proliferation and apoptosis of bone marrow cells, Western blot was used to detect the expression of signal transducer and activator of transcription 3 (STAT3), retinoic acid receptor-related orphan receptor γ (RORγt), transducer and activator of transcription 5 (STAT5) and fork head transcription factor 3 (Foxp3). RESULTS: Compared with the model group, the levels of Hb, RBC, WBC and PLT in the peripheral blood of mice in stanozolol and EPS group significantly increased, the proportion of Th17 cells was significantly reduced, and the proportion of Treg cells significantly increased. The levels of IL-2 and TNF-α in serum were significantly reduced (P<0.05), the level of IL-11 significantly increased (P<0.05), the number of bone marrow nucleated cells significantly increased (P<0.05), the positive rate of Ki-67 significantly increased (P<0.05) and the positive rate of Caspase-3 was significantly reduced (P<0.05). At the same time, the protein expression of STAT3 and RORγt significantly decreased, and the protein expression of STAT5 and Foxp3 increased, the difference showed statistically significant (P<0.05). CONCLUSION: EPS can promote the recovery of bone marrow hematopoietic function in AA mice and improve Th17/Treg imbalance, the mechanism may be related to the inhibition of STAT3/RORγt expression and promotion of STAT5/Foxp3 expression.

Identification of potential therapeutic antimicrobial peptides against Acinetobacter baumannii in a mouse model of pneumonia.

Acinetobacter baumannii-induced nosocomial pneumonia has become a serious clinical problem because of high antibiotic resistance rates. Antimicrobial peptides (AMP) are an ideal alternative strategy due to their broad-spectrum of antimicrobial activity and low incidence of bacterial resistance. However, their application is limited by toxicity and stability in vivo. The present study used a mouse model to directly identify potential AMPs effective for treatment of A. baumannii-induced pneumonia. Fifty-eight AMPs were screened and two identified (SMAP-29 and TP4) to have prophylactic effects which prevented the death of mice with pneumonia. Furthermore, two TP4 derivatives (dN4 and dC4) were found to have therapeutic activity in pneumonia mouse models by peritoneal or intravenous administration. Both dN4 and dC4 also inhibited and/or eliminated A. baumannii biofilms at higher doses. Taken together, these data suggest the AMP derivatives dN4 and dC4 represent a potential treatment strategy for A. baumannii-induced pneumonia.

Long non-coding RNA CIR inhibits chondrogenic differentiation of mesenchymal stem cells by epigenetically suppressing ATOH8 via methyltransferase EZH2.

BACKGROUND: Osteoarthritis (OA) is the most common articular disorder, leading to joint malfunction and disability. Although the incidence of OA is increasing globally, the treatment of OA is very limited. LncRNA CIR has been implicated in OA through unclear mechanisms. Here, we investigated the role of lncRNA CIR in chondrogenic differentiation. METHODS: Human umbilical-cord-derived mesenchymal stem cells (hUC-MSCs) were obtained from human umbilical cords. Flow cytometry was used to analyze the surface markers of hUC-MSCs. Various culture conditions and corresponding staining assays were employed to assess the differentiation abilities of hUC-MSC. qRT-PCR, western blot, and immunostaining were used to measure expression levels of related genes and proteins such as lncRNA CIR, ATOH8, EZH2, and H3K27me3. RNA immunoprecipitation assay, biotin pull-down, and chromatin immunoprecipitaion assay were performed to analyze the interactions of lncRNA CIR, EZH2, H3K27me3 and ATOH8 promoter. RESULTS: hUC-MSCs exhibited MSCs features and could differentiate into chondrocytes under specific conditions. LncRNA CIR was downregulated while ATOH8 was upregulated during the chondrogenic differentiation of hUC-MSCs. Knockdown lncRNA CIR or overexpression of ATOH8 promoted chondrogenic differentiation. Further, lncRNA CIR bound to EZH2 and repressed ATOH8 expression via EZH2-mediated H3K27me3, which promotes the methylation of ATOH8. Inhibition of ATOH8 reversed the effects of knockdown lncRNA CIR on chondrogenic differentiation. CONCLUSION: LncRNA CIR suppresses chondrogenic differentiation of hUC-MSCs. Mechanistically, lncRNA CIR could inhibit ATOH8 expression that functions to promote chondrogenic differentiation through EZH2-mediated epigenetic modifications.

Preliminary report of modified expansive laminoplasty in the treatment of thoracic ossification of the ligamentum flavum.

OBJECTIVE: This study was performed to evaluate the role of posterior suspension of the laminae-ossification of the ligamentum flavum complex combined with miniplate fixation (modified expansive thoracic laminoplasty) in treating thoracic ossification of the ligamentum flavum (TOLF). METHODS: Eight patients with TOLF treated by modified expansive thoracic laminoplasty were retrospectively analyzed. Their general information, operative time, intraoperative blood loss, and postoperative complications were recorded. Neurological functional recovery was evaluated by the modified Japanese Orthopaedic Association (mJOA) score and Hirabayashi recovery rate preoperatively, postoperatively, and at the final follow-up. Preoperative and postoperative imaging was performed, and the decompression range and internal fixation positioning were evaluated. RESULTS: The mJOA score significantly improved from 4.63 points preoperatively to 9.0 points at the final follow-up (Hirabayashi recovery rate of 77.75%). Postoperative computed tomography and magnetic resonance imaging revealed sufficient decompression of the surgical segment. At the final follow-up, the internal implants were well-placed, the lamina-ligamentum flavum complex showed no significant displacement, and neurological functional recovery was satisfactory. CONCLUSION: Surgical treatment of TOLF is complicated and high-risk. Characterized by simplicity and sufficient decompression, modified expansive thoracic laminoplasty can reduce the risk of cerebrospinal fluid leakage and nerve injury with satisfactory neurological functional recovery.

Localised delivery of quercetin by thermo-sensitive PLGA-PEG-PLGA hydrogels for the treatment of brachial plexus avulsion.

Accumulating evidence indicates that oxidative stress and inflammation are implicated in brachial plexus avulsion (BPA). Quercetin has anti-inflammatory, anti-oxidant, anti-apoptotic, and neuroprotective properties. This study investigated the therapeutic efficacy of a temperature-sensitive poly(D,L-lactide-co-glycolide)-poly(ethylene-glycol)-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) hydrogel sustained-release system of quercetin in BPA. In situ injections of the hydrogel loaded with different concentrations of quercetin were conducted in a rat model of BPA. Significantly reduced reactive oxygen species and interleukin-6 levels in the injured spinal cord 24 h post-surgery, increased number of anterior horn motor and functional neurons in the spinal cord 6 weeks post-surgery, thickened biceps muscle fibres and enlarged endplate area with clear structure, reduced demyelinated peripheral nerves, and significantly increased Terzis grooming test scores were found in the groups with 50 or 100 mg/mL quercetin-loaded hydrogels compared with the control and blank hydrogel groups. In conclusion, the temperature-sensitive quercetin loaded PLGA-PEG-PLGA hydrogel sustained-release system can alleviate oxidative damage and inflammation in the spinal cord, increase neuron survival rate, and promote nerve regeneration and motor function recovery in rats with early BPA. The findings suggest that this drug-loaded hydrogel has potential applications in the clinical treatment of BPA.

Pelvic dimension as a predictor of ureteral injury in gynecological cancer surgeries.

BACKGROUND: Ureteral injury is an intractable complication in gynecological cancer surgeries. Identifying risk factors can ensure safety of the ureters intraoperatively. A narrow pelvis is known to exert extra difficulties in pelvic surgeries. However, whether pelvic dimension can affect the risk of ureteral injury in gynecological cancer surgeries is poorly understood. We aimed to evaluate the association between pelvic dimension and the risk of ureteral injury during gynecological cancer surgeries. METHODS: All patients who had undergone gynecological cancer surgeries were searched from January 2011 to July 2017. We included patients with ureteral injury who had available data of abdominal and pelvic computed tomography for measuring pelvic dimensions. Multivariate condition logistic analysis was used to identify the risk factors independently correlated with ureteral injury in gynecological cancer surgeries. RESULTS: A total of 43 cases with 86 controls were included in this study. We discovered that a longer anteroposterior diameter of the mid-pelvis (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.01-1.13, P = 0.019) and a shorter transverse diameter of the mid-pelvis (OR 0.92, 95% CI 0.86-0.98, P = 0.013) were associated with ureteral injury in gynecological cancer surgeries. In laparoscopic analysis, a longer anteroposterior diameter of the mid-pelvis (OR 1.11, 95% CI 1.00-1.24, P = 0.041) was a risk factor for ureteral injury. In the analysis of open surgery, a longer transverse diameter of the mid-pelvis (OR 0.79, 95% CI 0.66-0.93, P = 0.006) was a protective factor for ureteral injury. CONCLUSIONS: This study demonstrated that mid-pelvis dimensions were associated with ureteral injury, but the observed differences were too small. In addition, pelvic inlet dimensions did not appear to relate with ureteral injury. Thus, these pelvimetry measures could not be beneficial in assessing the risk of ureteral injury in gynecological cancer surgeries.

MicroRNA-29a suppresses the invasion and migration of osteosarcoma cells by regulating the SOCS1/NF-κB signalling pathway through negatively targeting DNMT3B.

The present study aimed to investigate the roles of the microRNA­29a/DNA methyltransferase 3B/suppressor of cytokine signalling 1 (miR­29a/DNMT3B/SOCS1) axis in the invasion and the migration of osteosarcoma (OS). The expression levels of miR­29a, DNMT3B and SOCS1 were determined in tissue samples and OS cell lines by reverse transcription­quantitative polymerase chain reaction (PCR). Apoptosis was measured using flow cytometry analysis. Transwell and wound healing assays were conducted to measure the invasion and migration abilities of OS cells, respectively. A dual­luciferase reporter assay was also conducted to determine the interaction between DNMT3B and miR­29a, while methylation­specific PCR was used to detect the methylation of SOCS1. Western blotting was performed to determine the protein levels of DNMT3B and SOCS1, as well as the levels of proteins associated with epithelial­mesenchymal transition (EMT), apoptosis and the nuclear factor (NF)­κB signalling pathway. The results demonstrated that miR­29a and SOCS1 were downregulated, and DNMT3B was upregulated in both OS tissues and cell lines. The expression of miR­29a and SOCS1 was found to be associated with advanced clinical stage and distant metastasis. In addition, the dual­luciferase reporter assay revealed that DNMT3B was a direct target of miR­29a. Overexpression using miR­29a mimics decreased DNMT3B expression and the methylation level of SOCS1, which resulted in the upregulation of SOCS1 in U2OS and MG­63 cells, while miR­29a inhibition led to the opposite results. Transfection with miR­29a mimics also promoted the apoptosis, and inhibited the invasion, migration and EMT process of OS cells, while it markedly reduced the nuclear translocation of p65 and IκB­α degradation. Treatment with 5­aza­2'­deoxycytidine worked together with miR­29a mimics to synergistically enhance the aforementioned effects. By contrast, the effects induced by miR­29a were partly reversed upon co­transfection with SOCS1 siRNA. In conclusion, miR­29a promoted the apoptosis, and inhibited the invasion, migration and EMT process of OS cells via inhibition of the SOCS1/NF­κB signalling pathway by directly targeting DNMT3B.

Long non-coding RNA MEG3 inhibits chondrogenic differentiation of synovium-derived mesenchymal stem cells by epigenetically inhibiting TRIB2 via methyltransferase EZH2.

Osteoarthritis (OA) is a highly prevalent skeletal disease. Mesenchymal stem cell-derived cartilage tissue engineering is a clinical method used for OA treatment. Investigations on the molecular regulatory mechanisms of the chondrogenic differentiation of synovium-derived mesenchymal stem cells(SMSCs) will help promote its clinical applications. In this study, bioinformatics analysis from three different databases indicated that the long non-coding RNA (lncRNA) MEG3 may regulate the chondrogenic differentiation of SMSCs by targeting TRIB2. We then performed assays and found that both knockdown of MEG3 or overexpression of TRIB2 can stimulate the chondrogenic differentiation of SMSCs and increase Col2A1 and aggrecan expression. Knockdown of MEG3 can induce the expression of TRIB2; conversely, overexpression of MEG3 can inhibit the expression of TRIB2. Futhermore, knockdown of the TRIB2 can rescue the MEG3 silencing-mediated promotion of chondrogenic differentiation. Moreover, RNA immunoprecipitation(RIP) and RNA pull-down assays demonstrated that MEG3 can interact with EZH2, thus recruiting it to induce H3K27me3, which promotes the methylation of TRIB2 by binding with the promoter of TRIB2 in SMSCs. Additionally, EZH2 silencing significantly rescued the MEG3 overexpression-mediated inhibition of TRIB2 expression and chondrogenic differentiation of SMSCs. Taken together, these data indicated that MEG3 regulates chondrogenic differentiation by inhibiting TRIB2 expression through EZH2-mediated H3K27me3.