Effect of cotton dust on lungs among female workers in cotton industry in northern Gujarat,India

Byssinosis is a disabling occupational lung disease caused by cotton dust. It is a well-known occupational respiratory disease in cotton industry workers caused by cotton dust pollution. Many studies have been documented the effects of cotton dust on pulmonary function among workers employed in cotton-spinning mills. However, little data exist on the prevalence of this disorder in female workers particularly in western part of India. The present study was conducted to analyze the effects of exposure to cotton dust on pulmonary functions among female workers. The study was designed to assess the effects of exposure to cotton dust on lung functions among female cotton industry workers. Study group comprises 50 Female workers of cotton industry and control group comprises 50 age matched females who were neither worked in cotton industry nor exposed to cotton dust. Information was collected using standardized questionnaires, physical examination and spirometric measurements. Student''s T test was used to find the difference between spirometric parameters. All the respiratory parameters (FVC, FEV1, FEV1/FVC ratio, FEF 25-75 % PEFR and MVV) were reduced in cotton industry workers as compared with control subjects (p<0.0001) and no significant difference of SpO2 between groups. Cotton dust exposure makes huge impact on respiratory parameters of the cotton industry workers. This deterioration in respiratory health deteriorates with increasing duration of exposure. The health hazards caused by cotton dust should be controlled by creating awareness among the workers & employers.     

Thioredoxin and HSP90α modulate ASK1–JNK1/2 signaling in stressed hepatocytes of Mugil cephalus

Induction of antioxidant proteins like thioredoxin (Trx) and heat shock protein 90α (HSP90α) is a crucial step in the cellular response to oxidative stress. Here, we report the impact of environmental stress on Trx and HSP90α expressions in freshly isolated hepatocytes of Mugil cephalus living in either a contaminated (Test; Ennore) or uncontaminated (Control; Kovalam) estuary. Modulation in the activities of signal transduction molecules like apoptosis signal-regulating kinase 1 (ASK1) and c-Jun NH₂-terminal kinase 1/2 (JNK1/2) were also investigated to understand their functional role under natural stressed condition. The expression pattern of the proteins was determined by immunoblotting and the relationship between the proteins was identified by regression analysis. Test fish hepatocytes demonstrated significant upregulation (P < 0.05) in the levels of Trx and HSP90α and insignificant inductions in the expression pattern of ASK1 and JNK1/2 than control fish hepatocytes. These findings provide direct evidence that Trx and HSP90α induction in fish hepatocytes under stress may aid cell survival by negatively regulating ASK1 expression and thereby functionally antagonizing the apoptotic role of JNK1/2 in natural aquatic systems.     

Emodin Suppresses Migration and Invasion through the Modulation of CXCR4 Expression in an Orthotopic Model of Human Hepatocellular Carcinoma

Accumulating evidence(s) indicate that CXCL12-CXCR4 signaling cascade plays an important role in the process of invasion and metastasis that accounts for more than 80% of deaths in hepatocellular carcinoma (HCC) patients. Thus, identification of novel agents that can downregulate CXCR4 expression and its associated functions have a great potential in the treatment of metastatic HCC. In the present report, we investigated an anthraquinone derivative, emodin for its ability to affect CXCR4 expression as well as function in HCC cells. We observed that emodin downregulated the expression of CXCR4 in a dose-and time-dependent manner in HCC cells. Treatment with pharmacological proteasome and lysosomal inhibitors did not have substantial effect on emodin-induced decrease in CXCR4 expression. When investigated for the molecular mechanism(s), it was observed that the suppression of CXCR4 expression was due to downregulation of mRNA expression, inhibition of NF-κB activation, and abrogation of chromatin immunoprecipitation activity. Inhibition of CXCR4 expression by emodin further correlated with the suppression of CXCL12-induced migration and invasion in HCC cell lines. In addition, emodin treatment significantly suppressed metastasis to the lungs in an orthotopic HCC mice model and CXCR4 expression in tumor tissues. Overall, our results show that emodin exerts its anti-metastatic effect through the downregulation of CXCR4 expression and thus has the potential for the treatment of HCC.     

HSP70 expression and its role in preeclamptic stress

Preeclampsia, a hypertensive pregnancy-specific disorder, has long been analyzed for its association with cellular stress. It still remains one of the most serious complications of pregnancy. It is a multi-system disorder that affects maternal vascular function and fetal growth. The physiopathology of preeclampsia is still unclear, but an imbalance between reactive oxygen species (ROS) and antioxidants, appears to be an important contributing factor. Oxidative stress has been increasingly postulated as a major contributor to endothelial dysfunction in preeclampsia (PE). The ROS promotes lipid oxidation and are known to induce stress proteins, such as hemeoxygenase 1 (HO-1) and heat-shock protein 70 (HSP70). Embryonic and placental cells are highly sensitive to oxidative stress due to their proliferate nature. Endothelial cell dysfunction is suggested to be a part of wider maternal inflammatory reaction responsible for the clinical syndrome of preeclampsia. Part of the dysfunction in endothelial cell and trophoblast is attributed to oxidative stress developed during pregnancy. The disequilibrium in compensatory antioxidant control is proposed as a causative mechanism in the pathophysiology of preeclampsia. HSP70 acts as the secondary line of defense in systems with compromised antioxidant function. This article reviews the differential expression of HSP70 and the effect of mint-tea therapy to modulate preeclamptic oxidative damage.     

Synthesis and antibacterial property of quinolines with potent DNA gyrase activity

Synthesis of a series of novel tetrahydroquinoline annulated heterocycles has been accomplished by intramolecular imino and bisimino Diels–Alder reaction. These compounds were evaluated for their antibacterial activity. All the synthetic compounds, exhibited good antibacterial activity against microorganisms of which one of them 7 was found to be as active as the antibiotic ciplofloxacin and is found to have MIC value of 2.5 mg/mL against Escherichia coli.     

Antitumour activity of crocetin in accordance to tumor incidence, antioxidant status, drug metabolizing enzymes and histopathological studies

Lung cancer is the leading cause of cancer related mortality worldwide. Crocetin, saffron plant derivative known to play a role in cancer chemoprevention. In the present study the effects of crocetin was tested against lung cancer-bearing mice in both pre-initiation and post-initiation periods. Healthy male Swiss albino mice (6–8 weeks old) were used throughout the study. Experiment was designed with the treatment regimen of crocetin [20 mg/kg body weight dissolved in dimethyl sulphoxide (DMSO)] for 4 weeks before (pre-initiation) and from 12^th week after Benzo(a) pyrene B(a)p (50 mg/kg body weight) induced lung carcinoma(post-initation). The level of lipid peroxidation (LPO) and marker enzymes markedly increased in carcinogen administered animals, which was brought back to near normal by crocetin treatment. The activities of the enzymic antioxidants and glutathione metabolizing enzymes were decreased in B(a)p induced animals and increased upon drug treatment. Crocetin profoundly reverted back the pathological changes observed in cancerous animals. From the results crocetin proves to scavenge free radical and plays an important role in cellular function. Tumor incidence and histopathological studies proves crocetin is a potent antitumour agent.     

Role of thymine in protein coding frames of mRNA sequences

Distribution of thymine in protein coding mRNA sequences has been studied here. Our study suggest that thymine in protein coding sequences are not randomly distributed but with probability. Frame1 prefers to have definite amount of thymine. It is observed that the thymine content of frame 4 is also involved in protein coding. Frame 3 prefers to have least amount of thymine. However, frame 2 and frame 6 shows a variable degree of thymine content. The mRNA sequences of heterosexual animals, particularly, the human show a different distribution profile (less thymine in frame 1) compared to that of yeast and plants.     

Attenuation of 4-nitroquinoline 1-oxide induced in vitro lipid peroxidation by green tea polyphenols

Lipid peroxidation is believed to play an important role in pathogenesis of diseases. 4-Nitroquiunoline 1-oxide (4-NQO) a potent oral carcinogen, widely used for induction of oral carcinogenesis, was found to induce lipid peroxidation in vivo and in vitro. Green tea contains high content of polyphenols, which are potent antioxidants. Thus green tea polyphenols (GP) can play a protective role in 4-NQO induced in vitro lipid peroxidation. 4-NQO at the concentration of 1.5 mM was found to induce lipid peroxidation in 5% liver homogenate in phosphate buffered saline and extent of lipid peroxidation at the different time intervals 0, 15, 30 and 45 min where studied by assessing parameters such as hydroxyl radical production (OH), thiobarbituric acid reactants (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). It was found that addition of 4-NQO caused an increase in OH and TBARS level and a decrease in activity of SOD, CAT and the levels of GSH. Simultaneous addition of GP 10 mg/ml significantly decreased lipid peroxidation and increased in antioxidant status. Thus, we conclude that GP, a potent antioxidant, was found to nullify 4-NQO induced lipid peroxidation in vitro and 4-NQO acts initially by causing oxidative stress and leads to carcinogenesis.     

Structure-guided design,synthesis and biological evaluation of novel DNA ligase inhibitors with in vitro and in vivo anti-staphylococcal activity

A series of 2-amino-[1,8]-naphthyridine-3-carboxamides (ANCs) with potent inhibition of bacterial NAD⁺-dependent DNA ligases (LigAs) evolved from a 2,4-diaminopteridine derivative discovered by HTS. The design was guided by several highly resolved X-ray structures of our inhibitors in complex with either Streptococcus pneumoniae or Escherichia coli LigA. The structure–activity-relationship based on the ANC scaffold is discussed. The in-depth characterization of 2-amino-6-bromo-7-(trifluoromethyl)-[1,8]-naphthyridine-3-carboxamide, which displayed promising in vitro (MIC Staphylococcus aureus 1 mg/L) and in vivo anti-staphylococcal activity, is presented.     

CARd: Carbon distribution analysis program for protein sequences

Carbon distribution is responsible for stability and structure of proteins. Arrangement of carbon along the protein sequence is depends on how the amino acids are organized and is guided by mRNAs. An atomic level revision is important for understanding these codes. This will ultimately help in identification of disorders and suggest mutations. For this purpose a carbon distribution analysis program has been developed. This program captures the hydrophobic / hydrophilic / disordered regions in a protein. The program gives accurate results. The calculations are precise and sensitive to single amino acid resolution. This program is to help in mutational studies leading to protein stabilisation.