ABSTRACT
BACKGROUND: To investigate the efficacy of electroacupuncture for postoperative pain in mixed hemorrhoids. METHODS: Randomized controlled trials were searched in PubMed and Cochrane Library. The risk of bias assessment tool was used to assess methodological quality. Stata 14.0 software was used for meta-analysis. Weighted mean differences were calculated if all outcome variables were reported the same way, while standardized mean differences (SMD) were calculated if they were different. RESULTS: From 27 identified studies, 5 Chinese studies (465 patients) were included in this meta-analysis. The electroacupuncture group had significantly lower postoperative pain scores compared with the control group at 6 hours postoperatively (SMDâ =â -0.89, 95% CI: -1.091 to -0.692; Pâ <â .001), at 12 hours postoperatively (SMDâ =â -1.089, 95% CI: -1.336 to -0.843; Pâ <â .001), at 24 hours postoperatively (SMDâ =â -0.548, 95% CI: -0.721 to -0.374; Pâ =â .547), and 72 hours postoperatively (SMDâ =â -1.089, 95% CI: -1.336 to -0.843; Pâ <â .001). CONCLUSION: Electroacupuncture can improve pain after surgery for mixed hemorrhoids. It is an effective method to improve the pain after hemorrhoidectomy, which deserves further research and promotion.
Subject(s)
Electroacupuncture , Hemorrhoidectomy , Hemorrhoids , Humans , Hemorrhoids/surgery , Pain, Postoperative/therapy , PubMedABSTRACT
CXCR2 has emerged as a therapeutic target for not only peripheral inflammatory diseases but also neurological abnormalities in the central nervous system (CNS). Herein, we describe the discovery of a novel 1-cyclopentenyl-3-phenylurea series as potent and CNS penetrant CXCR2 antagonists. Extensive SAR studies, wherein molecules' property forecast index (PFI) was carefully optimized for overall balanced developability profiles, led to the discovery of the advanced lead compound 68 with a desirable PFI. Compound 68 demonstrated good in vitro pharmacology with excellent selectivity over CXCR1 and other chemokine receptors. Rat and dog pharmacokinetics (PK) revealed good oral bioavailability, high oral exposure, and desirable elimination half-life of the compound in both species. In addition, the compound demonstrated dose-dependent efficacy in the in vivo pharmacology neutrophil infiltration "air pouch" model in rodents after oral administration. Further, compound 68 is a CNS penetrant molecule with high unbound fraction in brain tissue.
Subject(s)
Brain/metabolism , Phenylurea Compounds/chemical synthesis , Phenylurea Compounds/pharmacology , Receptors, Interleukin-8B/antagonists & inhibitors , Animals , Biological Availability , CD11b Antigen/biosynthesis , Crystallography, X-Ray , Dogs , Dose-Response Relationship, Drug , Half-Life , Humans , Madin Darby Canine Kidney Cells , Male , Mice , Mice, Inbred C57BL , Models, Molecular , Neutrophil Infiltration/drug effects , Phenylurea Compounds/pharmacokinetics , Rats , Structure-Activity RelationshipABSTRACT
Structure-activity relationship exploration of the historical biarylurea series led to the identification of novel CNS penetrant CXCR2 antagonists with nanomolar potency, favorable PK profile, and good developability potentials. More importantly, the key compound 22 showed efficacy in a cuprizone-induced demyelination model with twice daily oral administration, thereby supporting CXCR2 to be a potential therapeutic target for the treatment of demyelinating diseases such as multiple sclerosis.
ABSTRACT
2-Aminopyrimidin-4(1H)-one was proposed as the novel bioisostere of urea. Bioisosteric replacement of the reported urea series of the CXCR2 antagonists with 2-aminopyrimidin-4(1H)-ones led to the discovery of the novel and potent CXCR2 antagonist 3e. 2-Aminopyrimidin-4(1H)-one derivative 3e demonstrated a good developability profile (reasonable solubility and high permeability) and superior chemical stability especially in simulated gastric fluid (SGF) compared with ureas.
Subject(s)
Pyrimidines/chemical synthesis , Receptors, Interleukin-8B/antagonists & inhibitors , Urea/analogs & derivatives , Humans , Molecular Structure , Pyrimidines/chemistry , Pyrimidines/pharmacology , Structure-Activity RelationshipABSTRACT
A novel series of nitrogen-containing flavonoids 5a-l, 6a,b, and 7a,b were designed and synthesized as cyclin-dependent kinases (CDKs) inhibitors. The representative compounds 5a, 5b, 5e, and 5g showed potent CDK1/Cyclin B inhibitory activities. All compounds displayed a significant growth inhibitory action in vitro against Bel-7402, PC-3, ECA-109, A-549, HL-60, and MCF-7 cancer cell lines. Flow cytometry analysis showed that 5b induced apoptosis in PC-3 cells.
