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. 相似文献
BackgroundThe use of personal-protection surgical helmet/hood systems is now a part of the standard surgical attire during arthroplasty in North America. There are no protocols for the disinfection of these helmets.MethodsThis is a prospective, single-center, observational study. Helmets worn by 44 members of the surgical team and foreheads of 44 corresponding surgical personnel were swabbed at three distinct time points. In addition, 16 helmets were treated with hypochlorite spray to determine if pathogens could be eliminated. Swabs obtained were processed for culture and next-generation sequencing (NGS).ResultsOf the 132 helmet samples, 97 (73%) yielded bacteria on culture and 94 (71%) had evidence of bacterial–deoxyribonucleic acid (DNA) on NGS. Of the swabs sent for bacterial identification at the three time points, at least one from each helmet was positive for a pathogen(s). Of the 132 forehead samples, 124 (93%) yielded bacteria on culture and 103 (78%) had evidence of bacterial-DNA on NGS. The most commonly identified organism from helmets was Cutibacterium acnes (86/132) on NGS and Staphylococcus epidermidis (47/132) on culture. The most commonly identified organism from the foreheads of surgical personnel was Cutibacterium acnes (100/132) on NGS and Staphylococcus epidermidis (70/132) on culture. Sanitization of helmets was totally effective; no swabs taken the following morning for culture and NGS identified any bacteria.ConclusionThis study demonstrates that surgical helmets worn during orthopedic procedures are contaminated with common pathogens that can potentially cause surgical site infections. The findings of this study should at the minimum compel us to develop protocols for the disinfection of these helmets. 相似文献
Whether prolonged operative time is an independent risk factor for subsequent surgical site infection (SSI) and periprosthetic joint infection (PJI) following total joint arthroplasty (TJA) remains a clinically significant and underexplored issue. The aim of this study is to investigate the association between operative time and the risk of subsequent SSI and PJI in patients undergoing primary TJA.
Methods
We retrospectively reviewed 17,342 primary unilateral total knee arthroplasty and total hip arthroplasty performed at a single institution between 2005 and 2016, with a minimum follow-up of 1 year. A multivariate logistic regression model was conducted to identify the association between operative time and the development of SSI within 90 days and PJI within 1 year.
Results
Overall, the incidence of 90-day SSI and 1-year PJI was 1.2% and 0.8%, respectively. Patients with an operative time of >90 minutes had a significantly higher incidence of SSI and PJI (2.1% and 1.4%, respectively) compared to cases lasting between 60 and 90 minutes (1.1% and 0.7%), and those lasting ≤60 minutes (0.9% and 0.7%, P < .01). In the multivariate model, the risk for infection increased by an odds ratio of 1.346 (95% confidential interval 1.114-1.627) for 90-day SSI and 1.253 (95% confidential interval 1.060-1.481) for 1-year PJI for each 20-minute increase in operative time.
Conclusion
In patients undergoing primary TJA, each 20-minute increase in operative time was associated with nearly a 25% increased risk of subsequent PJI. We advocate that surgeons pay close attention to this underappreciated risk factor while maintaining safe operative practices, which minimize unnecessary steps and wasted time in the operating room. 相似文献
Donor site morbidity following radial forearm flap (RFF) harvest remains a controversial issue. The aim of this meta-analysis was to answer the question “Are the range of wrist movements (range of motion, ROM) and hand strength affected after RFF harvesting?” The PubMed, Embase, Scopus, and Cochrane Library electronic databases were systematically searched (to December 2019). Self-controlled studies evaluating hand biomechanics after RFF harvest were included. Weighted mean differences with 95% confidence intervals were calculated using the random-effects model. The outcome variables were ROM, forearm movements, grip, and pinch strengths. Thirteen studies involving a total of 335 patients were included. With the exception of grip strength and supination, which showed statistically significant reductions of about 2.40 kg and 2.86° (P < 0.05), all other ROM, forearm movements, and pinch strengths showed an insignificant difference when the operated hand was compared to the non-operated hand (P > 0.05). Regression analysis showed that the method of donor site closure and size of the donor site defect had an insignificant impact on hand biomechanics. This study confirms the lack of discernible biomechanical morbidity after RFF transfer. The minimal reduction in hand biomechanics after RFF is considered to be clinically negligible. 相似文献
Butyrylcholinesterase (BChE) is a serine esterase that plays a role in the detoxification of natural as well as synthetic ester-bond-containing compounds. Alterations in BChE activity are associated with a number of diseases. Cholinergic system abnormalities in particular are correlated with the formation of senile plaques in Alzheimer’s disease (AD), and administration of cholinesterase inhibitors is a common therapeutic approach used to treat AD.
Here, our aim was to study the interaction between BChE and fluoxetine.
Molecular docking simulations revealed that fluoxetine penetrated deep into the active-site gorge of BChE and that it was engaged in stabilizing noncovalent interactions with multiple subsites. In substrate kinetic studies, the Vm, Km, kcat and kcat/Km values were found to be 20.59?±?0.36?U mg?1 protein, 194?±?14?µM, 1.3?×?108?s?1 and 6.7?×?105?µM?1s?1, respectively. Based on inhibitory studies, fluoxetine appeared to inhibit BChE competitively, with an IC50 value of 104?µM and a Ki value of 36.3?±?4.7?µM.
Overall, both the low Ki value and the high number of BChE–fluoxetine interactions suggest that fluoxetine is a potent inhibitor of BChE, although in vivo mechanisms for the direct effects of BChE inhibition on various pathologies remain to be further investigated.
In light of the pharmacophoric structural requirements for achieving anticonvulsant activity, a series of N-(1-methyl-4-oxo-2-un/substituted-1,2-dihydroquinazolin-3[4H]-yl)benzamide (4a-g) and N-(1-methyl-4-oxo-2-un/substituted-1,2-dihydroquinazolin-3[4H]-yl)-2-phenylacetamide (4h-n) derivatives were synthesized in two steps starting from the reaction of N-methyl isatoic anhydride with the appropriate hydrazide and followed by condensation with the appropriate aldehyde. The anticonvulsant activities of the synthesized compounds were evaluated according to the anticonvulsant drug development (ADD) programme protocol. Among the synthesized compounds, 4n showed promising activity in both the maximal electroshock (MES) and pentylenetetrazole (PTZ) tests with median effective dose (ED50) values of 40.7 and 6 mg/kg, respectively. The six most promising derivatives, 4b , 4a , 4c , 4f , 4j , and 4i , showed very low ED50 values in the PTZ test (3.1, 4.96, 8.68, 9.89, 12, and 13.53 mg/kg, respectively). All the tested compounds showed no to low neurotoxicity in the rotarod test with a wide therapeutic index. Docking studies of compound 4n suggested that GABAA binding could be the mechanism of action of these derivatives. The in silico drug likeliness parameters indicated that none of the designed compounds violate Lipinski's rule of five and that they are able to cross the blood–brain barrier.