Mechanism of action of Orthosiphon stamineus against non-alcoholic fatty liver disease: Insights from systems pharmacology and molecular docking approaches

Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of a metabolic syndrome caused by excessive accumulation of fat in the liver. Orthosiphon stamineus also known as Orthosiphon aristatus is a medicinal plant with possible potential beneficial effects on various metabolic disorders. This study aims to investigate the in vitro inhibitory effects of O. stamineus on hepatic fat accumulation and to further use the computational systems pharmacology approach to identify the pharmacokinetic properties of the bioactive compounds of O. stamineus and to predict their molecular mechanisms against NAFLD. Methods: The effects of an ethanolic extract of O. stamineus leaves on cytotoxicity, fat accumulation and antioxidant activity were assessed using HepG2 cells. The bioactive compounds of O. stamineus were identified using LC/MS and two bioinformatics databases, namely the Traditional Chinese Medicine Integrated Database (TCMID) and the Bioinformatics Analysis Tool for the Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Pathway enrichment analysis was performed on the predicted targets of the bioactive compounds to provide a systematic overview of the molecular mechanism of action, while molecular docking was used to validate the predicted targets. Results: A total of 27 bioactive compounds corresponding to 50 potential NAFLD-related targets were identified. O. stamineus exerts its anti-NAFLD effects by modulating a variety of cellular processes, including oxidative stress, mitochondrial β-oxidation, inflammatory signalling pathways, insulin signalling, and fatty acid homeostasis pathways. O. stamineus is significantly targeting many oxidative stress regulators, including JNK, mammalian target of rapamycin (mTOR), NFKB1, PPAR, and AKT1. Molecular docking analysis confirmed the expected high affinity for the potential targets, while the in vitro assay indicates the ability of O. stamineus to inhibit hepatic fat accumulation. Conclusion: Using the computational systems pharmacology approach, the potentially beneficial effect of O. stamineus in NAFLD was indicated through the combination of multiple compounds, multiple targets, and multicellular components.     

Tocilizumab en el tratamiento del rechazo humoral crónico activo resistente a terapia estándar

IntroductionThere is no consensus on the most appropriate treatment for chronic active antibody-mediated rejection (cAMR). Recent studies suggest that treatment with tocilizumab (TCZ) may stabilize graft function, decrease the intensity of donor-specific HLA antibodies (DSAs) and reduce inflammation of microcirculation.Patients and methodsObservational study with renal allograft recipients diagnosed with cAMR (n = 5) who had not submitted a response to traditional treatment based on the combination of plasma replacements, immunoglobulins, and rituximab. Patients were told to be treated with TCZ as compassionate use in six doses per month (8 mg/kg/month). Renal function, proteinuria, and the intensity of DSAs were monitored during follow-up.ResultsFive patients, average age 60 ± 13 years, three male and two retrasplants (cPRA average 55%) with preformed DSAs. Treatment with TCZ was initiated within 47 ± 52 days of biopsy. In two cases treatment was discontinued after the first dose, by severe bicitopenia with cytomegalovirus viremia and by graft failure, respectively. In the three patients who completed treatment, no stability of renal function (serum creatinine from 1.73 ± 0.70 to 2.04 ± 0.52 mg/dL, e-FGR 4 6 ± 15 to 36 ± 16 mL/min), showed increased proteinuria (3.2 ± 4.0 to 6.9 ± 11.0 g/g) and the intensity of DSAs maintain stable. No changes were observed in the degree of inflammation of microcirculation (g + pt 4.2 ± 0.8 vs. 4.3 ± 1.0) or in the degree of transplant glomerulopathy (cg 1.2 ± 0.4 vs. 1.8 ± 1.0).ConclusionsTCZ therapy does not appear to be effective in modifying the natural history of chronic active antibody-mediated rejection, does not improve the degree of inflammation of microcirculation and does not reduces the intensity of DSAs.     

Effectiveness and safety of extracorporeal shock wave treatment for low back pain：a systematic review and meta-analysis of RCTs

This meta-analysis was designed to assess the effectiveness and safety of extracorporeal shock wave therapy (ESWT) for patients with low back pain (LBP). Pubmed, Embase, Cochrane's library, PEDro (Physiotherapy Evidence Database), China National Knowledge Infrastructure (CNKI), and Wanfang Data were searched until December 2019 to identify studies assessing the effectiveness and safety of EPSW for LBP. The prime outcome is pain intensity measured by Visual Analog Scale (VAS) or numeric rating scale (NRS). Other outcomes included functional status, quality of life, psychological outcomes measured by Oswestry Disability Index (ODI), as well as the adverse events. Mean differences (MD) were calculated for continuous outcomes, while odd ratios (OR) were calculated for binary outcomes. Revman 5.3 software was used for statistical analysis. Five randomized controlled trials (RCTs) were finally included in this meta-analysis. The pooled mean difference in post-treatment pain scores was −2.37 (P ＜0.0001), indicating that post-treatment pain scores was significantly higher by 2.37 in control group than in ESWT group. At a mean follow-up time of 4–6 weeks, the pooled mean difference in ODI scores was −14.10 (P ＜0.00001), indicating that the pooled mean difference of post-treatment ODI scores was 14.10 higher in control group than in ESWT group. The use of ESWT is effective in alleviating pain and improving the general functional state for patients with LBP. However, more evidence was needed to verify its safety.     

The usefulness of measuring n-butyric acid concentration as a new indicator of blood decomposition in forensic autopsy

In forensic medicine, although various alcohols have been reported as indicators of decomposition in collected blood, no studies have examined short-chain fatty acids as indicators. In this study, the blood n-butyric acid concentration was quantified, and the association between n-butyric acid and decomposition was investigated to determine whether the detection of n-butyric acid could be a new indicator of decomposition. Among the forensic autopsies performed from 2016 to 2018 in our laboratory, the cases were divided into decomposed (n = 20) and non-decomposed (n = 20) groups based on macroscopic findings. Blood samples collected at the time of autopsy were derivatized with 3-nitrophenylhydrazine hydrochloride after solid-phase extraction. The n-butyric acid concentration was measured using liquid chromatography–tandem mass spectrometry. In addition, ethanol and n-propanol were measured using a gas chromatography-flame ionization detector. There was a significant difference (p < 0.01) in the concentrations of n-butyric acid between the decomposed and non-decomposed groups (0.343 ± 0.259 [0.030–0.973] and 0.003 ± 0.002 [0.001–0.007] mg/mL, respectively). In the decomposed group, n-butyric acid was detected at high concentrations, even in cases where n-propanol was low. These results suggest that n-butyric acid is more likely to be an indicator of blood decomposition than n-propanol.     

Validation of an on-screen application-based measurement of shoulder range of motion over telehealth medium

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A Mixed-Methods Study of the Effect of Abdominal Binders on Opioid Use and Postoperative Pain After Cesarean Birth

ObjectiveTo compare levels of postoperative oxycodone use and incisional pain between two randomized groups—an intervention and a control.DesignMixed-methods design; quantitative data achieved via a randomized controlled trial, with qualitative data collected on binder use. The primary variable was oxycodone (in milligrams) required during the first 48 hours after birth, and the secondary variable was incisional pain levels measured on Postoperative Days 1 and 2.SettingAcute-care community hospital in Wheat Ridge, Colorado, and an acute care urban hospital in Denver, Colorado.ParticipantsA total of 220 individuals in the postpartum period after having cesarean birth.Interventions/MeasurementsParticipants were randomized to the intervention group (binder) or the control group (no binder). Data were collected on opioid usage for the first 48 hours. Participants in both groups were asked to rate their incisional pain on Postoperative Day 1 (24 hours after birth) and Postoperative Day 2 (48 hours after birth). Participants in the binder group were also asked to provide feedback on their experience wearing the binder.ResultsA total of 196 participants completed the study. The overall amount of oxycodone taken by individuals in the binder group was lower than that in the control group, but the difference was not statistically significant (p = .10). Pain scores in the binder group were significantly lower on Day 2 compared with the control group (p = .002). The majority of individuals in the binder group provided positive feedback about their experience wearing the binder.ConclusionIndividuals routinely receive medications to assist with pain management postoperatively. Because of growing concerns related to the nation’s opioid addiction crisis, there is interest in using multimodal treatments to achieve adequate pain control for individuals postoperatively. Abdominal binders are a low-cost intervention to assist with pain management and, given the results of this study, seem like a reasonable option to consider.