Biosynthesis and characterization of Ocimum sanctum green silver nanoparticles and unravelling their enhanced anti-filarial activity through a HRAMS proteomics approach.

The available anti-filarial medications are largely ineffective against adult filarial worms. Also, these drugs have several drawbacks such as toxicity and development of resistance owing to long-term usage. Green nanomedicine may offer better solutions for Lymphatic Filariasis treatment due to its tiny size, biocompatibility, and better penetration at considerably lower costs with higher therapeutic efficacy. In the present study, Ocimum sanctum silver nanoparticles (OSAgNPs) were bio-synthesized and their anti-filarial efficacy was evaluated against adult filarial parasites. The green nanoparticles were characterized by UV-VIS spectroscopy, XRD, FTIR, SEM, and TEM analysis. The OSAgNPs significantly affected the motility and viability of adult Setaria cervi parasites after 4 h of incubation at concentrations higher than 0.5 µg ml-1. Proteomics analysis by high resolution accurate mass spectrometry revealed that 213 proteins were differentially expressed following OSAgNP treatment. Mostly these DEPs belonged to the many biochemical and molecular pathways of parasites such as muscle proteins, antioxidant proteins, heat shock proteins, signal recognition proteins, and energy metabolism-related proteins. Undoubtedly, this study will open new avenues for the development of novel anti-filarial drugs based on green nanoparticles.

Deciphering the anti-filarial potential of bioactive compounds from Ocimum sanctum: a combined experimental and computational study.

CONTEXT: The anthelminthic effect of Ocimum species (Lamiaceae) has been reported, however, its anti-filarial effect has not been explored to date. OBJECTIVE: This study evaluates the effect of Ocimum sanctum L. (OS) against lymphatic filarial parasites. MATERIAL AND METHODS: The ethanol extract of OS (EOS) leaves was tested for anti-filarial activity against Setaria cervi. Equal size and number (n = 10) of adult female S. cervi worms were incubated in 125, 250 or 375 µg/mL EOS extract for 6 h at 37 °C. The OS bioactive components were identified by UPLC-ESI-MS/MS and subjected to docking and molecular dynamics (MD) simulation against filarial antioxidant proteins. RESULTS: The EOS significantly inhibited the motility of adult female S. cervi after 6 h of incubation. The motility was found to be reduced by 53.7% in 375 µg/mL and 43.8% in 250 µg/mL EOS after 6 h of treatment. The UPLC-ESI-MS/MS analysis of ethanol extract of O. sanctum revealed the presence of 13 bioactive compounds. The docking analysis showed eight OS bioactive compounds to have high binding affinity (> 4.8 kcal/mol) towards antioxidant proteins of filarial parasites. Additionally, MD simulation studies showed significant impact of (RMSD ≤ 10 Å) chlorogenic acid, luteolin and ursolic acid on filarial antioxidant enzymes/proteins. To our knowledge, this is the first report of the anti-filarial activity of Ocimum sanctum. DISCUSSION AND CONCLUSIONS: The effect of EOS and OS bioactive components on human filarial parasites can be further evaluated for the development of new anti-filarial formulations.

Identification of promising nutraceuticals against filarial immune-modulatory proteins: insights from in silico and ex vivo studies.

Lymphatic filariasis is a neglected tropical disease affecting over 863 million people in 47 countries of the world. The anti-filarial drugs, diethylcarbamazine, albendazole, and ivermectin, are effective only at the larval stages and have proven completely ineffective as adulticides. Besides this, a long-term use of these drugs is associated with several side effects including drug toxicity. Nutraceuticals have emerged as better alternatives for long term treatments due to their safety and lesser side effects. In the present work, we have used drug docking analysis and molecular dynamics simulation approaches to explore the effect of anti-inflammatory nutraceuticals against the immune-modulatory proteins of filarial worms. The filarial proteins enolase, ES-62 precursor, serpin, and cystatin, which are highly efficient in host immune modulation were targeted with more than 50 nutraceuticals. In the in silico study nutraceuticals such as naringin, ß-carotene, and emodin showed higher binding efficacy and lower dissociation constant as compared to anti-filarial drugs. Molecular dynamics simulation results showed that immune-modulatory proteins formed highly stable complexes with naringin, ß-carotene, and emodin over the entire MD simulation run. The nutraceutical emodin formed the most stable system in silico and hence its effect was investigated on adult filarial parasites under ex vivo conditions too. Emodin significantly affected the motility, viability, ROS production, and genomic DNA fragmentation of filarial parasites. Further in vivo and in vitro studies will help in understanding the mechanism of action of emodin at the molecular level and would help in the development of more effective anti-filarial drugs.

Lymphatic filarial serum proteome profiling for identification and characterization of diagnostic biomarkers.

Lymphatic Filariasis (LF) affects more than 863 million people in tropical and subtropical areas of the world, causing high morbidity and long illnesses leading to social exclusion and loss of wages. A combination of drugs Ivermectin, Diethylcarbamazine citrate and Albendazole is recommended by WHO to accelerate the Global Programme to Eliminate Lymphatic Filariasis (GPELF). To assess the outcome of GPELF, to re-evaluate and to formulate further strategies there is an imperative need for high quality diagnostic markers. This study was undertaken to identify Lymphatic Filarial biomarkers which can detect LF infections in asymptomatic cases and would also serve as indicators for differentiating among different clinical stages of the disease. A combination of Fourier-transform infrared spectroscopy (FT-IR), MMP zymography, SDS-PAGE, classical 2DE along with MALDI-TOF/MS was done to identify LF biomarkers from serum samples of different stages of LF patients. FT-IR spectroscopy coupled with univariate and multivariate analysis of LF serum samples, revealed significant differences in peak intensity at 3300, 2950, 1645, 1540 and 1448 cm-1 (p<0.05). The proteomics analysis results showed that various proteins were differentially expressed (p<0.05), including C-reactive protein, α-1-antitrypsin, heterogeneous nuclear ribonucleoprotein D like, apolipoproteins A-I and A-IV in different LF clinical stages. Functional pathway analysis suggested the involvement of differentially expressed proteins in vital physiological pathways like acute phase response, hemostasis, complement and coagulation cascades. Furthermore, the differentiation between different stages of LF cases and biomarkers identified in this study clearly demonstrates the potential of the human serum profiling approach for LF detection. To our knowledge, this is the first report of comparative human serum profiling in different categories of LF patients.

A socio-ecological critique on India's local health traditions amidst rising incidence of global pandemics.

Introduction: The COVID-19 crisis has exposed inadequacy to deal with such health emergencies. The state of healthcare facilities in India is shambolic, which is further exacerbated by the exclusivity of modern health systems. The authors argue for vertical and horizontal expansion of the existing system to include traditional medicine systems, in favor of an urgently needed holistic and more inclusive healthcare system. Methods: Secondary data were collected from free online resources, including preprints, reprints and databases, J-gate Plus, PubMed and Web of Science, using keywords such as, "folk medicine", "folk medicine AND India", "traditional Indian medicines", "indigenous Indian medicines AND India", "Indian ethnomedicines", "Indian AND folk AND medicine", "indigenous Indian medicine". Results and conclusions: Insufficiently robust public healthcare infrastructure, lack of enough qualified health professionals, and poor use of its traditional medicinal systems, are limiting the access of basic healthcare facilities to a large section of the Indian population. Despite vehement opposition and criticism from modern health system practitioners, indigenous and local healing traditions do offer benefits and share a common global goal of health and healing. The objectives of Universal Health Coverage and Health for All as enshrined in the Sustainable Development Goals (SDGs) cannot be achieved without their involvement, especially in remote and economically disadvantaged regions of the country. Even a sub-optimal utilization of its biological and human resources and related traditional knowledge can not only profoundly change the health, but also the economic landscape of India. Here, we have nuanced the constrains posed by the emerging health challenges, status and prospects of the great and little traditions of the Indian System of Medicines in fulfilling the urgent healthcare needs of the country. The authors based their arguments on the available evidence, rather than emotive ideas or, as a fan of Indian traditional medicines, and suggest for the purposeful inclusion of traditional health systems and practitioners more actively in India's health care delivery systems. The country must not squander the opportunities offered by its traditional medicinal systems.

Carbonate-Based Fluorescent Chemical Tool for Uncovering Carboxylesterase 1 (CES1) Activity Variations in Live Cells.

Carboxylesterase 1 (CES1) plays a key role in the metabolism of endogenous biomolecules and xenobiotics including a variety of pharmaceuticals. Despite the established importance of CES1 in drug metabolism, methods to study factors that can vary CES1 activity are limited with only a few suitable for use in live cells. Herein, we report the development of FCP1, a new CES1 specific fluorescent probe with a unique carbonate substrate constructed from commercially available reagents. We show that FCP-1 can specifically report on endogenous CES1 activity with a robust fluorescence response in live HepG2 cells through studies with inhibitors and genetic knockdowns. Subsequently, we deployed FCP-1 to develop a live cell fluorescence microscopy-based approach to identify activity differences between CES1 isoforms. To the best of our knowledge, this is the first application of a fluorescent probe to measure the activity of CES1 sequence variants in live cells.

Identification of glucose regulated protein94 (GRP94) in filarial parasite S. cervi and its expression under ER stress.

GRP94, a member of HSP90 family, is involved in folding and degradation of endoplasmic reticulum proteins. The proteome analysis of Setaria cervi, a bovine filarial parasite showed that a 91 kDa protein was over expressed, after the parasites were maintained in glucose deprived medium. The MALDI- LC/MS analysis of the 91 kDa band confirmed it as endoplasmin precursor (GRP94). Amino acid sequence alignment of S.cervi GRP94 exhibited maximum similarity with human filarial parasite Wuchereria bancrofti, Brugia malayi and Loa loa GRP94. Tunicamycin treatment of S. cervi worms revealed that the expression of GRP94 is associated with ER stress. Transcription of S. cervi grp94 as well as igf is regulated by transcription factors ATF-6 and XBP-1S which was confirmed by Real Time PCR. Moreover, marked alteration in the expression of igf after 3 h and 6 h of drug treatment suggested propagation of survival pathway under ER stress. The activities of ER stress markers protein disulphide isomerase and glycosyltransferase were significantly reduced after 6 h of tunicamycin treatment. The present findings thus indicate that the expression of GRP94 and regulation of its expression is under ER stress in Setaria cervi. To our knowledge this is the first report of identification of GRP94, in any filarial parasite till date.

Human carboxylesterases and fluorescent probes to image their activity in live cells.

Human carboxylesterases (CESs) are serine hydrolases that are responsible for the phase I metabolism of an assortment of ester, amide, thioester, carbonate, and carbamate containing drugs. CES activity is known to be influenced by a variety of factors including single nucleotide polymorphisms, alternative splicing, and drug-drug interactions. These different factors contribute to interindividual variability of CES activity which has been demonstrated to influence clinical outcomes among people treated with CES-substrate therapeutics. Detailed exploration of the factors that influence CES activity is emerging as an important area of research. The use of fluorescent probes with live cell imaging techniques can selectively visualize the real-time activity of CESs and have the potential to be useful tools to help reveal the impacts of CES activity variations on human health. This review summarizes the properties of the five known human CESs including factors reported to or that could potentially influence their activity before discussing the design aspects and use considerations of CES fluorescent probes in general in addition to highlighting several well-characterized probes.

Role of anti-filarial drugs in inducing ER stress mediated signaling in bovine filarial parasitosis Setaria cervi.

In this ex vivo study, S. cervi parasitoses were treated with Ivermectin (50 µM), Albendazole (200 µM) alone and Ivermectin + Albendazole (50 + 200 µM) at 37°C for 8 h and the motility and viability of the parasitoses were evaluated. Individually both drugs Ivermectin (Iver) and Albendazole (Alb) are reported to affect the function and integrity of ER, however till date, no reports are available on the functional changes in ER due to a combined Iver and Alb treatment of bovine helminth parasitosis. Here, we report the lethal effect of a combination treatment of Iver and Alb against adult bovine filarial parasitosis Setaria cervi. The underlying mechanism of drug action was elucidated by performing a systematic biochemical, molecular and proteomics based study. Altered calcium homeostasis in drug treated parasitoses lead to reduction in levels of total Endoplasmic Reticulum (ER) calcium by 50 % and 61 % and elevation by 50 % and 63 % in cytosol in Iver alone and Iver + Alb treated parasitoses respectively. Further, it was found that upregulated expression of ER localized GRP94, galactosyltransferase and glycosyltransferase activity in addition to reduction in activity of PDI indicated ER stress mechanisms being operative under combined drug treatment. Marked rise of 79 % reactive oxygen species and reduced antioxidant levels induced oxidative stress in drug treated parasitosis. The collective effect of both ER and oxidative stress might have triggered apoptosis, as evidenced by the elevated calpain activity, reduction of 67 % in cytochrome c oxidase and 83 % rise in caspase-3 activity in the Iver + Alb treated parasitoses respectively. The ER proteome analysis by 2D gel electrophoresis revealed 76 spots in the control and 56 spots in the treated proteome. A MALDI-MS/MS analysis of some of the differentially expressed spots of the combination drug treated parasitoses identified glucuronosyltransferase as a major upregulated protein with a fold change of 1.81. Trafficking protein, acyl transferase, MATH involved in protein folding were also found to be downregulated. Thus, this study based on biochemical and proteomic approaches indicates that a combination of anti-filarial drugs Iver and Alb can alter calcium homeostasis in bovine filarial parasitosis leading to induction of ER stress culminating into apoptosis.

Role of HRCT Temporal Bone in Pre-operative Assessment of Tegmen Height in Chronic Otitis Media Patients.

OBJECTIVES: High-resolution CT (HRCT) temporal bone has emerged as a useful option in pre-operative assessment of tegmen height in chronic otitis media patients. MATERIAL AND METHODS: A total of 60 patients with clinical suspicion of chronic otitis media were enrolled in the study. HRCT evaluation was done using Siemens Somatom Force 384 slice multidetector computed tomography machine. We radiologically assess tegmen height using lateral semicircular canal as a reference point on HRCT. Final result has been based on correlation of radiological and intraoperative findings. Diagnostic efficacy of HRCT temporal bone was evaluated in terms of sensitivity, specificity, PPV, NPV, and accuracy for pre-operative assessment of tegmen height. RESULTS: The correlation between actual tegmen height and estimated tegmen height (by equation) was 0.457 which is highly significant (P < 0.001). In the study, the mean tegmen height of exposed dura (ED) was 5.81 ± 1.71 (95% CI 4.91-6.70) while the mean tegmen height of non-exposed dura (NED) was 8.40 ± 1.31 (95% CI 8.02- 8.78). Highly significant difference was found in mean tegmen height between ED and NED cases (P < 0.001). CONCLUSION: Pre-operative CT assessment of tegmen height is an important parameter in assessing risk of dural injury during tympanomastoid surgeries.

Dual-Energy Computed Tomography Lung in patients of Pulmonary Tuberculosis.

OBJECTIVES: The objective of this study was to characterize findings of high-resolution computed tomography (HRCT) and dual-energy CT (DECT) (80 keV, 140 keV, and mixed) in pulmonary tuberculosis (TB) patients and to compare and correlate HRCT and DECT findings. MATERIAL AND METHODS: This cross-sectional study was conducted on 67 patients of 18-65 years of age who were suspected cases of pulmonary TB with signs and symptoms of cough, fever, hemoptysis, sputum, night sweats, and weight loss with positive sputum AFB examinations/bronchoalveolar lavage. All the patients subjected to HRCT scan and followed with DECT scan. Comparison of various imaging techniques (DECT 80 keV, DECT 140 keV, and DECT mixed) with HRCT was done for detecting lung findings and data so obtained were subjected to statistical analysis. RESULTS: On comparing the various imaging techniques with HRCT for detecting consolidation, tree in bud pattern, cavitary lesions, ground-glass opacity, bronchiectasis, atelectasis, nodules, granuloma, peribronchial thickening, and fibrosis, the maximum agreement of HRCT was found with DECT 80 keV and minimum agreement was found with DECT 140 keV. CONCLUSION: The study concluded that DECT 80 keV monochromatic reconstructions among 80 keV, mixed, and 140 keV monochromatic reconstructions in lung parenchyma window settings are a faster and better analytical tool for the assessment of findings of pulmonary TB when compared with HRCT.

Role of Dual-Energy Computed Tomography in Characterization of Ureteric Calculi and Urinary Obstruction.

Objective The present study was carried out to assess the accuracy of dual-energy computed tomography (DECT) in the morphological and chemical characterization of ureteric calculi along with the prediction of the grade of urinary obstruction. Methods This was a prospective observational study that included 100 cases with ultrasonography (USG)-diagnosed ureteric calculi that underwent surgery or had spontaneous expulsion of ureteric calculi. At enrolment, DECT was performed for an in vivo evaluation of volume, chemical composition, and grade of obstruction by subjective assessment of the perinephric edema. After surgical intervention, in vitro evaluation of volume was done by fluid displacement followed by infrared spectroscopy (IRS) for chemical composition. DECT findings were compared with the biochemical analysis and degree of obstruction was validated against excretory CT urograms. Sensitivity, specificity, and the positive predictive and negative predictive values of DECT were assessed. Results No significant difference was observed between the mean volume of stones by fluid displacement (65.1±77.61 mm3) and DECT assessment (66.09±81.78 mm3). IRS revealed the composition of stones as hydroxyapatite, uric acid, cysteine, oxalic acid, and mixed type in 48, 23, 15, five, and nine cases. The sensitivity and specificity of DECT for hydroxyapatite, uric acid, cysteine, oxalic acid, and mixed types were 89.6% and 88.5%, 82.6% and 97.5%, 86.7% and 96.5%, 80% and 98.9%, and 88.9% and 98.9%, respectively. On CT urography, a total of 35 had a high-grade and 65 had a low-grade obstruction, whereas DECT revealed high- and low-grade obstructions in 42 and 58 cases. The sensitivity and specificity of DECT for a high-grade obstruction were 94.3% and 86.2%. Conclusions The findings of the study showed that DECT provides comprehensive information regarding the morphological, chemical, and anatomical characterization of ureteric stones.

Diagnostic Accuracy of Multidetector CT in Detection of Early Interstitial Lung Disease With Its Role in Characterization.

Background Multidetector CT (MDCT) has emerged as a useful option for early diagnosis of interstitial lung disease (ILD) with adequate accuracy. Methods A total of 80 patients with restricted pulmonary functions and clinical suspicion of ILD were enrolled in the study. MDCT evaluation was done using Siemens Somatom Force 384 slice multidetector computer tomography machine. Pattern analysis for reticular opacities, nodules and lung opacities was done to reach at a diagnosis. Final diagnosis was based on correlation of radiological and clinicopathological findings. Diagnostic efficacy of MDCT was evaluated in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for detection of ILD. Results Mean age of patients was 58 ± 8.75 years. Majority were females (51.3%). History of chronic obstructive pulmonary disease (COPD), tuberculosis and bronchial asthma was revealed in 31 (38.8%), 26 (32.5%) and 16 (20%) patients, respectively. There were 30 (37.5%) patients having no history of respiratory diseases. MDCT diagnosed ILD in 45 (56.3%) cases. On final diagnosis, ILD was diagnosed in 35 (43.8%) cases (15 usual interstitial pneumonia [UIP], 9 cryptogenic organizing pneumonia [COP], 8 nonspecific interstitial pneumonia [NSIP] and 3 respiratory bronchiolitis associated interstitial lung disease [RBILD]). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of MDCT in detection of ILD was 91.4%, 71.1%, 71.1%, 91.4% and 80%, respectively. Conclusion MDCT as a single modality had a high sensitivity for detection of ILD and could be recommended as first line diagnostic imaging technique.

A Comparative Assessment Between High-resolution Ultrasonography and Field Magnetic Resonance Imaging in Supraspinatus Tear Cases and Its Arthroscopic Correlation.

Background Diagnosis of a supraspinatus tear in patients presenting with shoulder pain is a difficult task and often requires the help of an MRI. However, in recent years, high-resolution ultrasonography (USG) has been utilized as a cheaper yet sensitive alternative. The aim of the study is to provide a comparative assessment of supraspinatus tears between USG and MRI in relation to arthroscopic results. Methods A total of 60 patients with shoulder pain for the last three months or more scheduled to undergo arthroscopic surgery for their shoulder disorder were enrolled; those having any congenital deformity of the shoulder or having any contradiction to an MRI were excluded from the assessment. All the patients underwent high-resolution ultrasonography (HRUSG) and MRI evaluation. Both the USG and MRI findings were correlated with the arthroscopic findings. Results On ultrasonography, 34 (56.67%) full-thickness tears and 22 (36.67%) partial-thickness tears of the supraspinatus were detected. On MRI, 36 (60.0%) were diagnosed as a full-thickness tear and 20 (33.33%) as a partial-thickness tear. After arthroscopy, 36 (60.00%) were confirmed as a full-thickness tear and 20 (33.33%) as a partial-thickness tear of the supraspinatus. For a full-thickness tear, the sensitivity and specificity of USG and MRI were 95.0% and 92.5%, and 85% and 92.5%, respectively. For a full-thickness tear, the sensitivity and specificity of the modalities were 94.4% and 100%, respectively. Conclusion HRUSG and MRI both had high comparable accuracy for detection of a supraspinatus tear, however, HRUSG had an edge over MRI in the detection of a partial tear.

Exogenous supplementation of N-acetylcysteine Can Reduce Hepatotoxicity Induced by Ascites Fluid (Cell-Free) Adsorbed Over Protein-A-Containing Staphylococcus aureus Cowan-I Without Compromising Its Antitumor Effect.

INTRODUCTION: Hepatotoxicity along with enhanced mortality has remained a major concern during the development of antitumor therapy with the use of cell-free ascites fluid adsorbed (ad-AF) over Protein-A-containing Staphylococcus aureus Cowan I (SAC). Major issue with ad-AF inoculation is the significant depletion of hepatic glutathione (GSH). Exogenous supplementation of -SH contents to the host has offered an encouraging hope to explore the possibilities to use ad-AF as a therapeutic material due to its antitumor effects. GSH and l-cysteine have shown a promise with the recovery of -SH contents as well as the recovery of phase I and phase II biotransformation enzymes. Aforementioned observations prompted us to try other -SH donors. MATERIALS AND METHODS: Therefore, in this study, N-acetylcysteine (NAC) was used as an exogenous source to provide -SH contents to reduce hepatotoxicity and mortality induced by ad-AF treatment. RESULTS: Exogenous supplementation of NAC along with ad-AF treatment to ascites tumor bearers has shown a significant protection against hepatotoxicity and mortality caused by ad-AF. NAC substitution along with ad-AF has significantly enhanced the mean survival time (MST), without altering the antitumor effect of ad-AF as evident from tumor cell counts and viability. DISCUSSION: NAC supplementation has been successful to recover hepatic -SH contents along with the significant recovery of phase I and phase II biotransformation enzymes. Marker enzymes for liver injury have also given clear-cut indications for the recovery of tumor bearers from hepatotoxicity induced by ad-AF. CONCLUSION: This study has shown that exogenous supplementation of NAC protects the host from the enhanced mortality and hepatotoxicity induced by ad-AF. These observations offer a hope to develop ad-AF as one of the probable treatment strategies for ascites tumors at least at experimental levels.

Cysteine Supplementation Mitigates the Toxicity Associated with Antitumor Therapy of Ehrlich's Ascites Fluid Adsorbed over Protein A Containing Staphylococcus aureus Cowan I.

INTRODUCTION: Previously, we have reported the amelioration of ad-AF induced hepatotoxicity with the exogenous supplementation of glutathione (GSH) without compromising the anti-tumor effect of ad-AF in ascites tumor model of mice with transplantable Ehrlich's Ascites Tumor cells. Cellular uptake of glutathione (GSH) has its own limitations, therefore exogenous supplementation of L-cysteine (Cys) was tried to reduce the toxicity of ad-AF by providing -SH contents without compromising the anti-tumor property of adsorbed ascites fluid (ad-AF). RESULTS: A significant increase in mean survival time (MST) of tumor bearing mice from 18.1 days to 32.9 days with exogenous supplementation of Cys was observed. Cys supplementation did not alter decline in body-weight gain, tumor cell counts as well as decrease in the viability of tumor cells in ascites tumor bearing animals. Similarly, Cys has been helpful to restore the hepatic -SH contents upto the levels of -SH content in tumor control group. The exogenous supplementation of Cys along with ad-AF has been helpful to restore the decline in the activities of phase-I and enhanced levels of glutathione-S-transferase (GST). The changes in the activities of different enzymes of phase-I and phase-II indicate the reduction in toxic insult induced by the therapeutic material (ad-AF). However, ad-AF treatment could not prevent tumor bearers from natural death due to tumor progression but significantly reduced the rate of tumor progression. CONCLUSIONS: Our study suggests that exogenous supplementation of Cys alongwith ad-AF could have a potential to be developed as a modality for the treatment of ascites tumor at least at experimental level.

An insight into the significance of the DnaK heat shock system in Staphylococcus aureus.

The bacterium Staphylococcus aureus utilizes a variety of different mechanisms to survive unfavorable stress conditions that are critical for its persistence in the environment and for pathogenicity. The staphylococcal DnaK heat shock system functions as a major protein folding machine under stress conditions that cause aggregation and un-folding of proteins. In prior studies, S. aureus cells with a non-functional DnaK system showed reduced tolerance to heat, oxidative and antibiotic stresses, a lowered carotenoid production, and decreased survival in a murine host. This study provides insights that the altered phenotypes of the dnaK mutant cells are not due to decreased SigB activity in the mutant cell. Transcriptomic profiling studies provide evidence that a large number of genes encoding proteins involved in cell wall biogenesis, virulence and general stress tolerance, and genes encoding proteins involved in metabolic processes are differentially regulated in dnaK mutant cells relative to wild-type S. aureus. It was also determined that loss of functional DnaK caused a reduction in the ability of S. aureus to make biofilms and its adherence to eukaryotic cells. This study provides evidence of a global significance of DnaK heat shock system in S. aureus.

Contribution of CNS cells in NeuroAIDS.

NeuroAIDS is becoming a major health problem among AIDS patients and long-term HIV survivors. As per 2009 estimates of UNAIDS report, more than 34 million people have been infected with HIV out of which ≥ 50% show signs and symptoms of neuropsychiatric disorders. These disorders affect central nervous system (CNS) and peripheral nervous systems (PNS). CNS is one of the most protected organ systems in body which is protected by blood-brain barrier (BBB). Not only this, most of the cells of CNS are negative for receptors and co-receptors for HIV infections. Neurons have been found to be completely nonpermissive for HIV infection. These facts suggest that neurotoxicity could be an indirect mechanism responsible for neuropsychiatric complications. In this review, we will discuss the importance of different cell types of CNS and their contribution toward neurotoxicity.