Biomolecular evidence of anti-inflammatory effects by Clematis mandshurica Ruprecht root extract in rodent cells

Ethnopharmacological relevance

Clematis mandshurica Ruprecht root is widely used in Asia as an analgesic and anti-inflammatory agent. This research investigated the anti-inflammatory effects of Clematis mandshurica Ruprecht root extract (CRE) using RAW 264.7 macrophage cells and carrageenan- (CA-) induced rat paw edema.

Materials and methods

Production of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, nitric oxide (NO) and prostaglandin E₂ (PGE₂) in the culture supernatant, mRNA expression of TNF-α, IL-1β, IL-6, iNOS and COX-2, protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) in the extract were assayed. In addition, the effect of CRE on acute inflammation in vivo was observed using CA-induced rat hind paw edema assay. The changes on the histopathology and histomorphometry of hind paw skins—dorsum and ventrum pedis were observed using CA-treated rats.

Results

Treatment with CRE (0.25, 0.5, and 1 mg/mL) resulted in inhibited levels of protein expression of lipopolysaccharide- (LPS-) induced iNOS, COX-2, NF-κB, and MAPKs (ERK, JNK, and p38) as well as production of TNF-α, IL-1β, IL-6, NO, and PGE₂ induced by LPS. Consistent with these results, CRE reduced the LPS-induced expressions of these cytokines, iNOS and COX-2 at the mRNA levels in a dose-dependent manner. In particular, results of the CA-induced rat hind paw edema assay showed an anti-edema effect of CRE. In addition, treatment with CRE resulted in dose-dependent inhibition of CA-induced increases of skin thickness, mast cell degranulation, and infiltrated inflammatory, TNF-α, IL-1β, iNOS, and COX-2-positive cells in both dorsum and ventrum pedis skin, respectively.

Conclusions

These results demonstrate that CRE exhibits anti-inflammatory activities via decreasing production of pro-inflammatory mediators through suppression of the pathways of NF-κB and MAPKs in LPS-induced macrophage cells. In addition, results of the CA-induced rat hind paw edema assay show an anti-edema effect of CRE. Our findings also support the traditional use of CRE in the inflammatory symptoms of rheumatic arthritis and acute icteric hepatitis. Thus, CRE may have therapeutic potential for a variety of inflammation-mediated diseases and may be developed into potent anti-inflammatory drugs.     

Uwhangchungsimwon,a traditional herbal medicine,protects brain against oxidative injury via modulation of hypothalamus–pituitary–adrenal (HPA) response in a chronic restraint mice model

Ethnopharmacological relevance

Uwhangchungsimwon (UCW) is a representative traditional herbal medicine for central nervous system disorders in East Asia countries over thousand years. To evaluate the pharmacological effects of UCW against oxidative brain injury in a chronic restraint stress mice model.

Methods and materials

C57BL/6 male mice underwent daily oral administration of distilled water, UCW or ascorbic acid 1 h before induction of restraint stress (5 h of immobilization daily for 14 days). Nitric oxide (NO), total reactive oxygen species (ROS) levels, malondialdehyde, protein carbonyl contents, and activities of antioxidant enzymes, and concentrations of corticosterone, adrenaline, noradrenaline, and dopamine, were measured in brain tissues or sera.

Results

Restraint stress notably increased NO and ROS levels, malondialdehyde and protein carbonyl contents in brain tissues, but decreased activities of catalase, glutathione reductase and glutathione peroxidase. These alterations were significantly ameliorated by UCW. UCW significantly attenuated the elevated serum concentrations of corticosterone, adrenaline and noradrenaline. UCW also significantly normalized the gene expressions in brain tissues altered by restraint stress; up-regulation of phenylethanolamine N-methyltransferase (PNMT) and N-methyl-d-aspartate type 1 receptor (NMDAR1), and down-regulation of gamma-Aminobutyric acid type A receptor (GABAAR), glutamate decarboxylase 1 (GAD 67), and glutamate decarboxylase 2 (GAD 65), respectively. Moreover, UCW considerably restored neurogenesis in the hippocampal regions which was disturbed by chronic restraint stress.

Conclusions

These results evidenced that UCW has pharmacological properties for brain protection and neurogenesis in status of stress-associated oxidative damage, and the underlying mechanisms involve the regulation of HPA axis in stress responses.     

The Effect of Intramural Myomas Without an Intracavity Component on In Vitro Fertilization Outcomes in Single Fresh Blastocyst Transfer Cycles

Study Objective

To assess clinical pregnancy rate (CPR) and live birth rate (LBR) in the presence of non–cavity-deforming intramural myomas in single fresh blastocyst transfer cycles.

Voice outcomes of polyacrylamide hydrogel injection laryngoplasty

OBJECTIVES: Polyacrylamide hydrogel (PAAG, Aquamid) is widely used as permanent facial tissue filler during facial plastic surgery. In this study, we examined the long-term effects and safety aspects of PAAG as a vocal fold augmentation material for patients with permanent unilateral vocal cord paralysis. STUDY DESIGN: Prospective clinical trials. METHODS: PAAG injection laryngoplasty was performed in 34 consecutive patients with permanent unilateral vocal cord paralysis. Percutaneous injection was performed under local anesthesia into the vocalis muscle using disposable 25 gauge long needles. Of the 34 patients, 16 completed acoustic, perceptual, stroboscopic, and subjective evaluations prior to the injection and at 6 and 12 months after the injection. RESULTS: Acoustic and perceptual parameters (GRBAS [Overall grade of dysphonia, Roughness, Breathiness, Aesthenia, Strain], Maximal phonation time [MPT], jitter, and shimmer) were significantly improved (P < .05) after injection and remained stable over 12 months. The grades of mucosal waves and glottic closure were also significantly improved (P < .01). The voice handicap index (VHI), as well as the visual analogue scale (VAS) of hoarseness and aspiration significantly improved over 12 months. No adverse effects were observed except for a decrease in the mucosal wave of one patient, after injection into a superficial area of the vocal fold. CONCLUSION: Based on the preliminary results of this trial, PAAG appears to be a long-lasting and safe injection material that is suitable for the treatment of glottal insufficiency caused by permanent unilateral vocal cord paralysis.     

Potentiation of cadmium-induced cytotoxicity by sulfur amino acid deprivation through activation of extracellular signal-regulated kinase1/2 (ERK1/2) in conjunction with p38 kinase or c-jun N-terminal kinase (JNK). Complete inhibition of the potentiated toxicity by U0126 an ERK1/2 and p38 kinase inhibitor.

The mechanisms of cadmium-induced toxicity may include oxidative stress, altered redox homeostasis, and injuries to organelles. The current study was designed to study the effect of decreased cellular glutathione (GSH) content by sulfur amino acid deprivation on cadmium toxicity and to identify the signaling pathways responsible for the cytotoxicity. GSH content was increased by cadmium in H4IIE cells prior to cell death, which was prevented by excess GSH or cysteine. Cell viability, however, was not improved by GSH or cysteine complexation of cadmium. Cadmium-induced cytotoxicity was 40-fold potentiated in cells with decreased GSH by sulfur amino acid deprivation. Cadmium in combination with decreased GSH markedly increased apoptotic cell death. Mitogen-activated protein kinases including extracellular signal-regulated kinase 1/2, p38 kinase and c-Jun N-terminal kinase (JNK) were all activated 1-12 hr after sulfur amino acid deprivation. U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene), which inhibited activation of extracellular signal-regulated kinase1/2 and p38 kinase in cells under sulfur amino acid deprivation, completely prevented potentiation in Cd-induced cytotoxicity and apoptosis. Potentiation of cadmium toxicity by sulfur amino acid deprivation was prevented in part by either PD98059 or SB203580, or in cells stably expressing dominant negative mutant of JNK1, and to greater extents by PD98059 in combination with either SB203580 or JNK1(-) transfection. These results demonstrated that decreased cellular GSH content potentiated cytotoxicity induced by cadmium at the level of human exposure, and that the potentiation of cytotoxicity resulted from activation of extracellular signal-regulated kinase1/2 in conjunction with p38 kinase or JNK.     

Safety and Efficacy of Everolimus-Eluting Bioresorbable Vascular Scaffold Versus Second-Generation Drug-Eluting Stents in Real-World Practice

BackgroundThe risk of device thrombosis and device-oriented clinical outcomes with bioresorbable vascular scaffold (BVS) was reported to be significantly higher than with contemporary drug-eluting stents (DESs). However, optimal device implantation may improve clinical outcomes in patients receiving BVS. The current study evaluated mid-term safety and efficacy of Absorb BVS with meticulous device optimization under intravascular imaging guidance.MethodsThe SMART-REWARD and PERSPECTIVE-PCI registries in Korea prospectively enrolled 390 patients with BVS and 675 patients with DES, respectively. The primary endpoint was target vessel failure (TVF) at 2 years and the secondary major endpoint was patient-oriented composite outcome (POCO) at 2 years.ResultsPatient-level pooled analysis evaluated 1,003 patients (377 patients with BVS and 626 patients with DES). Mean scaffold diameter per lesion was 3.24 ± 0.30 mm in BVS group. Most BVSs were implanted with pre-dilatation (90.9%), intravascular imaging guidance (74.9%), and post-dilatation (73.1%) at proximal to mid segment (81.9%) in target vessel. Patients treated with BVS showed comparable risks of 2-year TVF (2.9% vs. 3.7%, adjusted hazard ratio [HR], 1.283, 95% confidence interval [CI], 0.487–3.378, P = 0.615) and 2-year POCO (4.5% vs. 5.9%, adjusted HR, 1.413, 95% CI, 0.663–3.012, P = 0.370) than those with DES. The rate of 2-year definite or probable device thrombosis (0.3% vs. 0.5%, P = 0.424) was also similar. The sensitivity analyses consistently showed comparable risk of TVF and POCO between the 2 groups.ConclusionWith meticulous device optimization under imaging guidance and avoidance of implantation in small vessels, BVS showed comparable risks of 2-year TVF and device thrombosis with DES.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02601404","term_id":"NCT02601404"}}NCT02601404, {"type":"clinical-trial","attrs":{"text":"NCT04265443","term_id":"NCT04265443"}}NCT04265443     

Study on Electrical Pitting Prevention Device of a Rotating Shaft Using Automatic Control Potential Balancing

A rotating body consisting of a rotating shaft and bearings inevitably generates voltage and current. The potential difference between the bearing and the shaft is the main cause of electrical corrosion, which causes motor failure, shortened bearing life, and many safety issues. To prevent corrosion, passive shaft-grounding devices use conductive materials and brushes; however, these devices cannot be completely grounded, so there is a difference in local potential, and brush friction generates a shaft current. The cumulative effect causes electrical corrosion; therefore, in this study, an electrical corrosion protection device for the rotating power supply shaft was developed. It detected current and potential difference and established a feedback system on the rotating shaft. It also energized the rotating shaft using an external power supply to eliminate the potential difference on the shaft and reduce electrical corrosion. The result was prolonged motor life and improved stability, operating efficiency, and operability of related equipment. In this study, a rotating-shaft test rig was set up, and a constant current was applied to simulate the potential difference and verify the performance of the anti-corrosion device. Gradually, the design scheme was optimized; the potential difference on the rotating shaft was accurately quantified; and the goal of controlling the potential difference within 2 mV was achieved. Finally, the electrical corrosion protection device was applied to the rotating shaft of a merchant ship, and the current and potential difference on the rotating shaft were monitored for 30 days. The results showed that the device had excellent performance in reducing the potential difference on the rotating shaft and preventing electrical corrosion.     

Full-Endoscopic versus Minimally Invasive Lumbar Interbody Fusion for Lumbar Degenerative Diseases : A Systematic Review and Meta-Analysis

ObjectiveAlthough full-endoscopic lumbar interbody fusion (Endo-LIF) has been tried as the latest alternative technique to minimally invasive transforaminal lumbar interobody fusion (MIS-TLIF) since mid-2010, the evidence is still lacking. We compared the clinical outcome and safety of Endo-LIF to MIS-TLIF for lumbar degenerative disease. MethodsWe systematically searched electronic databases, including PubMed, EMBASE, and Cochrane Library to find literature comparing Endo-LIF to MIS-TLIF. The results retrieved were last updated on December 11, 2020. The perioperative outcome included the operation time, blood loss, complication, and hospital stay. The clinical outcomes included Visual analog scale (VAS) of low back pain and leg pain and Oswestry disability index (ODI), and the radiological outcome included pseudoarthosis rate with 12-month minimum follow-up. ResultsFour retrospective observational studies and one prospective observational study comprising 423 patients (183 Endo-LIF and 241 MIS-TLIF) were included, and the pooled data analysis revealed low heterogeneity between studies in our review. Baseline characteristics including age and sex were not different between the two groups. Operation time was significantly longer in Endo-LIF (mean difference [MD], 23.220 minutes; 95% confidence interval [CI], 10.669–35.771; p=0.001). However, Endo-LIF resulted in less perioperative blood loss (MD, -144.710 mL; 95% CI, 247.941–41.478; p=0.023). Although VAS back pain at final (MD, -0.120; p=0.586), leg pain within 2 weeks (MD, 0.005; p=0.293), VAS leg pain at final (MD, 0.099; p=0.099), ODI at final (MD, 0.141; p=0.093) were not different, VAS back pain within 2 weeks was more favorable in the Endo-LIF (MD, -1.538; 95% CI, -2.044 to -1.032; p<0.001). On the other hand, no statistically significant group difference in complication rate (relative risk [RR], 0.709; p=0.774), hospital stay (MD, -2.399; p=0.151), and pseudoarthrosis rate (RR, 1.284; p=0.736) were found. ConclusionRelative to MIS-TLIF, immediate outcomes were favorable in Endo-LIF in terms of blood loss and immediate VAS back pain, although complication rate, mid-term clinical outcomes, and fusion rate were not different. However, the challenges for Endo-LIF include longer operation time which means a difficult learning curve and limited surgical indication which means patient selection bias. Larger-scale, well-designed study with long-term follow-up and randomized controlled trials are needed to confirm and update the results of this systematic review.     

Triple Therapy-Based on Tegoprazan,a New Potassium-Competitive Acid Blocker,for First-Line Treatment of Helicobacter pylori Infection: A Randomized,Double-Blind,Phase III,Clinical Trial

Background/AimsWe examined the efficacy and safety of tegoprazan as a part of first-line triple therapy for Helicobacter pylori eradication.MethodsA randomized, double-blind, controlled, multicenter study was performed to evaluate whether tegoprazan (50 mg)-based triple therapy (TPZ) was noninferior to lansoprazole (30 mg)-based triple therapy (LPZ) (with amoxicillin 1 g and clarithromycin 500 mg; all administered twice daily for 7 days) for treating H. pylori. The primary endpoint was the H. pylori eradication rate. Subgroup analyses were performed according to the cytochrome P450 (CYP) 2C19 genotype, the minimum inhibitory concentration (MIC) of amoxicillin and clarithromycin, and underlying gastric diseases.ResultsIn total, 350 H. pylori-positive patients were randomly allocated to the TPZ or LPZ group. The H. pylori eradication rates in the TPZ and LPZ groups were 62.86% (110/175) and 60.57% (106/175) in an intention-to-treat analysis and 69.33% (104/150) and 67.33% (101/150) in a per-protocol analysis (non-inferiority test, p=0.009 and p=0.013), respectively. Subgroup analyses according to MICs or CYP2C19 did not show remarkable differences in eradication rate. Both first-line triple therapies were well-tolerated with no notable differences.ConclusionsTPZ is as effective as proton pump inhibitor-based triple therapy and is as safe as first-line H. pylori eradication therapy but does not overcome the clarithromycin resistance of H. pylori in Korea (ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT03317223","term_id":"NCT03317223"}}NCT03317223).