Synthesis of water soluble copper(II) complexes: crystal structures,DNA binding,oxidative DNA cleavage,and in vitro anticancer studies

Two ternary copper(II) complexes of dl-threonine and polypyridyl ligands with formula of [Cu(Thr)(Byp)Cl]·H₂O (1) and [Cu(Thr)(Phen)H₂O]Cl·2H₂O (2) were synthesized. The complexes were characterized by spectral (NMR, FT-IR, and UV–Vis), CHN elemental analysis and have been structurally elucidated by X-ray crystallography. Both of the complexes formed slightly distorted square-pyramidal coordination geometry. The electronic absorption spectra of the complexes showed a very low intensity d–d electronic band in the range of 610–620 nm in Tris–HCl/NaCl (5:5 mM) pH 7.2 buffer solution. The DNA binding interaction with calf-thymus DNA (CT-DNA) was investigated by electronic absorption spectral titration and viscosity measurements. The results revealed that the phenanthroline complex (2) interact with CT-DNA through intercalation while bipyridyl complex (1) through the groove binding mode. The calculated intrinsic binding constant (K _b) of (1) and (2) were 0.5 and 4.4 × 10⁵ M^?1, respectively. Both the complexes were found to promote efficient DNA cleavage activities at low concentration in the presence of H₂O₂. The results showed that (2) has the highest DNA binding and nuclease activity. Furthermore, both the complexes were tested against human colon cancer (HCT 116) and breast cancer (MCF-7) cell lines and showed a dose-dependent antiproliferation effect.     

Unsymmetrical 1,3-disubstituted urea derivatives as α-chymotrypsin inhibitors

The objective of this study was to synthesize potent and/or novel inhibitors for α-chymotrypsin activity. Eighteen derivatives of N-methylphenyl-N′-(alkyl/aryl) urea (1–18) were synthesized, and their inhibitory effects on α-chymotrypsin enzyme were evaluated. Two compounds exhibited potent inhibitory activities. The most potent, N-(2-methylphenyl)-2-oxo-1-pyrrolidinecarboxamide (15) having a methyl group at ortho position was the most active inhibitor with an IC₅₀ value of 8.10 ± 0.14 μM, which was comparable to standard chymostatin (IC₅₀ = 8.24 ± 0.11 μM). A slightly less potent, N-(2-acetylphenyl)-N′-(3-methylphenyl) urea (10), exhibited an IC₅₀ of 13.6 ± 0.23 μM. Compounds 3, 4, 7, 11, and 13 exhibited moderate activities. The results demonstrated that α-chymotrypsin inhibition is related to the position of the methyl group and the presence of substituent at the nitrogen of the urea bridge. The inhibitory trend suggests that α-chymotrypsin inhibitory activity declines with ortho > meta > para substitution order. In conclusion, our data suggest that the compound 15 may serve as a lead compound for further designing of other potent or novel α-chymotrypsin inhibitors.     

Hyperbaric oxygen for the treatment of nonhealing arterial insufficiency ulcers

There is limited data regarding hyperbaric oxygen's effectiveness in the treatment of nonhealing arterial insufficiency ulcers. This study was designed to analyze healing rates and amputation rates in patients who underwent adjunctive hyperbaric oxygen for a nonhealing arterial insufficiency ulcer. A retrospective chart review was completed on patients who underwent hyperbaric oxygen for arterial insufficiency ulcers that failed to heal despite standard treatment. Information collected included complete ulcer healing, amputation, and patient characteristics. There were 82 patients identified. A majority did not have diabetes (84.1%). The overall rate of healing was 43.9%. The overall major amputation rate was 17.1%. The amputation rate among those who healed was 0% compared to 42.4% among those not healed (p < 0.0001). Dialysis was predictive of major amputation (p = 0.03). Our findings suggest hyperbaric oxygen can play a role in management of arterial insufficiency ulcers that have failed standard treatment. The overwhelming majority of these patients did not have diabetes, which allows this study to be translated to patients with a primary arterial insufficiency ulcer. These results support the use of hyperbaric oxygen for select nonhealing arterial insufficiency ulcers that have failed standard therapy and the need for a prospective pilot study.     

Progesterone in transient ischemic stroke: a dose–response study

Rationale

Previous studies demonstrate the neuroprotective effects of progesterone in numerous animal injury models, but a systematic dose–response study in a transient ischemic stroke model is lacking.

Objectives

We investigated the effects of progesterone at different doses on post-stroke brain infarction and functional deficits in middle-aged rats.

Methods

Cerebral ischemia was induced in 13-month-old male Sprague–Dawley rats by right middle cerebral artery occlusion for 2 h followed by reperfusion. Rats received intraperitoneal injections of 8, 16, or 32 mg/kg of progesterone (P8, P16, P32) or vehicle at 2 h post-occlusion followed by subcutaneous injections at 6 h and every 24 h post-injury for 7 days. Functional recovery was evaluated at intervals over 22 days using motor, sensory, and cognitive tests. Infarct size was evaluated at 22 days post-stroke.

Results

Repeated-measures ANOVA showed significant group effects on grip strength, rotarod, and sensory neglect. All progesterone-treated groups had improved (p?p?Conclusions Although all doses were somewhat effective, progesterone given at 8 mg/kg led to the most consistent improvements across a panel of behavioral/functional tests and reduced the severity of ischemic infarct injury.     

Berberine attenuates adverse left ventricular remodeling and cardiac dysfunction after acute myocardial infarction in rats: Role of autophagy

The present study aimed to test the hypothesis that berberine, a plant‐derived anti‐oxidant, attenuates adverse left ventricular remodelling and improves cardiac function in a rat model of myocardial infarction (MI). Furthermore, the potential mechanisms that mediated the cardioprotective actions of berberine, in particular the effect on autophagy, were also investigated. Acute MI was induced by ligating the left anterior descending coronary artery of Sprague‐Dawley rats. Cardiac function was assessed by transthoracic echocardiography. The protein activity/levels of autophagy related to signalling pathways (e.g. LC‐3B, Beclin‐1) were measured in myocardial tissue by immunohistochemical staining and western blot. Four weeks after MI, berberine significantly prevented cardiac dysfunction and adverse cardiac remodelling. MI rats treated with low dose berberine (10 mg/kg per day) showed higher left ventricular ejection fraction and fractional shortening than those treated with high‐dose berberine (50 mg/kg per day). Both doses reduced interstitial fibrosis and post‐MI adverse cardiac remodelling. The cardioprotective action of berberine was associated with increased LC‐3B II and Beclin‐1 expressions. Furthermore, cardioprotection with berberine was potentially related to p38 MAPK inhibition and phospho‐Akt activation. The present in vivo study showed that berberine is effective in promoting autophagy, and subsequently attenuating left ventricular remodelling and cardiac dysfunction after MI. The potential underlying mechanism is augmentation of autophagy through inhibition of p38 MAPK and activation of phospho‐Akt signalling pathways.     

A Nontraditional Faculty Development Initiative Using a Social Media Platform

Objective. To assess the outcomes from an 11-year nontraditional professional development activity implemented by female faculty members at several colleges and schools of pharmacy.Design. Within the context of an online fantasy football league, faculty members practiced community-based faculty development strategies, including peer mentoring, skills development, constructive feedback and other supportive behaviors.Assessment. Data were extracted from curriculum vitae to characterize the academic progress of participants and to quantify scholarly work collaborations among league members. Analyses were limited to members who had participated in the league for 10 or more consecutive years. Seventy-one collaborative scholarly works occurred among team managers, including presentation of 20 posters and 2 oral presentations at national or international meetings, publication of 29 peer-reviewed articles and 15 book chapters, and funding of 5 research projects.Conclusion. Social media platforms can foster nontraditional faculty development and mentoring by enhancing connectivity between pharmacy educators who share similar interests.     

An Exploratory Study on Resistance Spot Welding of Titanium Alloy Ti-6Al-4V

Resistance spot welding (RSW) is one of the most effective welding methods for titanium alloys, in particular Ti-6Al-4V. Ti-6Al-4V is one of the most used materials with its good ductility, high strength, weldability, corrosion resistance, and heat resistance. RSW and Ti-6Al-4V materials are often widely used in industrial manufacturing, particularly in automotive and aerospace industries. To understand the phenomenon of resistance spot weld quality, the physical and mechanical properties of Ti-6Al-4V spot weld are essential to be analyzed. In this study, an experiment was conducted using the Taguchi L9 method to find out the optimum level of the weld joint strength. The given optimum level sample was analyzed to study the most significant affecting RSW parameter, the failure mode, the weld nugget microstructure, and hardness values. The high heat input significantly affect the weld nugget temperature to reach and beyond the β-transus temperature. It led to an increase in the weld nugget diameter and the indentation depth. The expulsion appeared in the high heat input and decreased the weld nugget strength. It was caused by the molten material ejection in the fusion zone. The combination of high heat input and rapid air cooling at room temperature generated a martensite microstructure in the fusion zone. It increased the hardness, strength, and brittleness but decreased the ductility.