Synthesis,biological evaluation and in silico molecular docking of novel 1-hydroxy-naphthyl substituted heterocycles

The versatile precursor 2-acetyl-4-allyl-1-hydroxy naphthalene was synthesized efficiently via Claisen rearrangement 2-acetyl-1-allyloxynaphthalene. The Claisen-Schmidt condensation of latter precursor afforded the corresponding chalcones which were exploited to synthesize a series of potential heterocycles such as pyrazoline, isoxazoline, benzocoumarin and benzoflavone. The synthesized products showed potent antioxidant and antimicrobial activities. Chalcone 3c, naphthyl pyrazoline 6b and hydroxycoumarin 13 exhibited the highest activity as antioxidants. Their binding mode showed specialized recognition of hydroxycoumarin 13 with the triad key amino acids at the active site of the oxidoreductase enzyme (PDB code 1DXO). 1-Hydroxynaphth-2-yl pyrazoline (6b) revealed the highest efficacy against both Gram positive and negative bacterial species. In silico molecular docking of pyrazoline 6b endorsed its proper binding at the active site of the 2EX6 enzyme which explains its potent antibacterial activity in comparison with standard ampicillin.     

Higher rate of hyperglycemia than hypoglycemia during Ramadan fasting in patients with uncontrolled type 1 diabetes: Insight from continuous glucose monitoring system

Background

Patients with uncontrolled type 1 diabetes mellitus (T1DM) are at a high risk for Ramadan fasting and are exempt from fasting; however, most still insist on fasting. The aim of this study was to examine glucose level fluctuations in those patients during Ramadan fasting using a real-time continuous glucose monitoring system (RT-CGMS).

Impact of occupational cadmium exposure on bone in sewage workers

Cadmium (Cd) is one of the environmental risk factors for bone loss. The present study included 40 sewage workers occupationally exposed to Cd. Forty nonexposed men were included as a control group. Current smokers represented 65% and 47.5% of the exposed and control groups, respectively.

The study aimed to investigate the hazard of occupational Cd exposure on bone health. This was achieved through measuring serum and urinary Cd, and calcium (Ca), in addition to serum osteoprotegerin (OPG) and estrogen receptor-α gene. Results showed significant elevation in serum Cd, OPG, and urinary Ca levels in the exposed compared to the controls. Bony aches and joint pain were more prevalent among the exposed workers. Serum and urinary Cd increased in exposed smokers relative to control smokers. Also, serum OPG levels showed significant rise among exposed smoker and nonsmoker compared to control smoker and nonsmoker groups. Serum Cd level increased significantly in PP and pp genotypes in exposed workers compared to controls, while elevated levels of serum OPG was observed in PP and Pp genotypes in exposed workers relative to controls.

Urinary Cd exhibited significant rise in both PP and pp genotypes in exposed workers, while Ca excretion was elevated in pp genotype only. The study reflected an association of genetic predisposition and Cd exposure in progression of osteoporosis. Further research is needed to explain the mechanisms of Cd impact on bone. The role of smoking is important and hence smoking cessation programs are essential for sewage workers.     

A 5′ AMP‐Activated Protein Kinase Enzyme Activator,Compound 59, Induces Autophagy and Apoptosis in Human Oral Squamous Cell Carcinoma

5′ AMP‐activated protein kinase enzyme (AMPK), a master regulator of cellular metabolism, is recognized for its association with various metabolic diseases, inflammation and cancer. In this study, we aimed to investigate the role of compound 59, an AMPK activator, in a panel of oral squamous cell carcinoma (OSCC) cell lines. The antiproliferative effects of compound 59 were assessed by MTT assays, flow cytometry, Western blotting, confocal microscopy and transmission electron microscopy. Relative to OSCC cells, normal human oral keratinocytes were almost insensitive to compound 59 treatment. Compound 59 induced apoptosis as indicated by caspase activation and PARP cleavage. In addition, it inhibited JAK/STAT3 signalling, arrested cells in the G1 phase, increased reactive oxygen species (ROS) generation and promoted autophagy. Interestingly, pre‐treatment with a protein tyrosine phosphatase (PP2A) inhibitor, cantharidin, partially reversed compound 59‐induced down‐regulation of p‐JAK2 and p‐STAT3, thereby suggesting the involvement of a protein tyrosine phosphatase. Together, these findings substantiate the potential of compound 59 for the treatment of OSCC patients.     

Insulin resistance and idiopathic infertility: A potential possible link

Among various health issues, infertility has been always considered as one of the major health problems. Idiopathic infertility is still a matter of debate since the underlying mechanisms stay obscure. Idiopathic infertility is related to expanded chance of metabolic syndrome components, obesity and increased risk of cardiovascular diseases. This study aimed to assess insulin resistance and serum levels of irisin as one of the adipokines in patients with idiopathic infertility. This study included 50 male patients aged 25–50 years old suffering from idiopathic infertility, together with 50 healthy individuals of matched age as controls. Patients showed significantly increased homeostasis model assessment for insulin resistance values than controls. For irisin results, idiopathic infertility patients had significantly decreased values than controls indicating the potential effect of irisin in development of insulin resistance in idiopathic infertility patients.     

Three-dimensional characterisation of the globe position in the orbit

Graefe's Archive for Clinical and Experimental Ophthalmology - Current methods to analyse the globe position, including Hertel exophthalmometry and computed tomography (CT), are limited to the...     

Depression in Behçet’s disease patients: Relationship with disease pattern,activity and quality of life

Aim of the workTo determine the frequency of depression in Behçet’s disease (BD) patients and to clarify its burden on patients’ clinical manifestations, disease activity status and quality of life (QoL).Patients and methods35 BD patients with 35 matched control were included in this study. Disease activity was assessed by Behçet Syndrome Activity Score (BSAS). All participants were requested to complete the Hamilton depression rating scale (HDRS), Multidimensional assessment of fatigue (MAF) questionnaire and the short form-36 (SF-36) QoL Scale.ResultsThe mean age of the patients was 40.3 ± 13.5 years (17–72 years) and they were 27 males and 8 females. The frequency of depression in BD patients was 74.3% with increased male frequency (p = 0.007) and major organ involvement (p = 0.04) among depressed patients. Significant differences (p < 0.001, p = 0.04, p = 0.001 respectively) between depressed and non depressed BD patients with respect to BSAS, MAF and SF-36. Highly significant positive correlations between HDRS and number of major organ, BSAS, MAF, (p < 0.001) and significant correlation with number of non major organs (r = 0.3, p = 0.04). Significant negative associations were observed between HDRS and SF-36 (r = ?0.6, p < 0.001). On regression number of major organ involvement (p < 0.001), BSAS (p = 0.01), MAF (p = 0.002), and SF-36 QoL (p < 0.001) significantly correlated with HDRS.ConclusionDepression is a significant comorbidity in patients with BD and is closely related to fatigue, number of major organ involvement and overall disease activity with a negative impact on QoL. Therefore, early interference and depression management in routine clinical practice is important to reduce patients’ symptoms, and improve QoL.