MCC950 reduces autophagy and improves cognitive function by inhibiting NLRP3-dependent neuroinflammation in a rat model of Alzheimer's disease.

Alzheimer's disease (AD) is the seventh most common cause of mortality and one of the major causes of disability and vulnerability in the elderly. AD is characterized by gradual cognitive deterioration, the buildup of misfolded amyloid beta (Aß) peptide, and the generation of neurofibrillary tangles. Despite enormous scientific progress, there is no effective cure for AD. Thus, exploring new treatment options to stop AD or at least slow down its progress is important. In this study, we investigated the potential therapeutic effects of MCC950 on NLRP3-mediated inflammasome-driven inflammation and autophagy in AD. Rats treated with streptozotocin (STZ) exhibited simultaneous activation of the NLRP3 inflammasome and autophagy, as confirmed by Western blot, immunofluorescence, and co-immunoprecipitation analyses. MCC950, a specific NLRP3 inhibitor, was intraperitoneally administered (50 mg/kg body weight) to rats with AD-like symptoms induced by intracerebroventricular STZ injections (3 mg/kg body weight). MCC950 effectively suppressed STZ-induced cognitive impairment and anxiety by inhibiting NLRP3-dependent neuroinflammation. Moreover, our findings indicate that MCC950 exerts neuroprotective effects by attenuating autophagy in neuronal cells. The inhibiting effects of MCC950 on inflammasome activation and autophagy were reproduced in vitro, provding further mechansistic insights into MCC950 therapeutic action. Our findings suggest that MCC950 impedes the progression of AD and may also improve cognitive function through the mitigation of autophagy and NLRP3 inflammasome inhibition.

Microbes as a tool for the bioremediation of fish waste from the environment and the production of value-added compounds: a review.

Fish are the most edible protein source worldwide and generate several remnants such as scales, viscera, head, bone, and skin. Fish wastes are not disposed of properly, which adversely affects the environment, especially the water bodies where fish processing industries dispose of their waste. Fish waste mainly contains nitrogen, oil, fat, salts, heavy metals, and organic compounds, which increase the biological oxygen demand and chemical oxygen demand. Fish waste can degrade in various ways, such as physicochemical or by enzymatic action, but using microbes is an environmentally friendly approach that can provide valuable compounds such as products such as collagen, chitin, minerals, and fish protein concentrates. This review is designed to focus on the suitability of microbes as tools for fish waste degradation and the production of certain associated. This study also provides insight into the production of other compounds such as protease, chitinase, and chitin applicability of these products. After processing, fish waste as a microbial growth media for enzyme production since microorganisms synthesize enzymes such as proteases, protein hydrolysates, lipids, and chitinase, which have broader applications in the pharmaceutical, cosmetic, biomedical material, and food processing industries.

ACE Gene I/D Polymorphism and Cardiometabolic Risk Factors: A Cross Sectional Study of Rural Population.

The D allele has been identified as being linked to cardiovascular disease since the discovery of an insertion/deletion (I/D) polymorphism in the ACE gene, this polymorphism has been found to have significant associations with a variety of cardiovascular risk factors. Recent findings indicate a rising prevalence of metabolic disorders among rural populations in developing nations. Research on health matters has been predominantly focused on urban populations, with relatively less attention given to their rural counterparts Hence, the present study attempts to estimate the prevalence of ACE gene I/D polymorphism and explore its association with various cardiovascular risk factors among Rural Yadav population from India. In the present study, 207 (Male 47, Female 160) members of the Yadav community participated in the cross-sectional study. All the socio-demographic factors, somatometric (anthropometric) variables, and the intravenous blood was collected and Physiological (blood pressure), and biochemical (fasting glucose and lipid profile) parameters were measured as recommended by the American Heart Association, allele-specific PCR of the ACE gene I/D polymorphism was carried out, the PCR products were genotyped on 2% agarose gel Electrophoresis and ACE gene polymorphism was analysed for its association with various cardiovascular risk factors. Among the analysed individuals, 34 (16.4%) were found to have the II genotype, 58 (28.0%) had the ID genotype, and 115 (55.6%) had the DD genotype. The allele frequency of the I allele was found to be 0.31, and the frequency of the D allele was 0.69. The frequency of the DD genotype was found to be significantly higher among individuals with high TC, high TG, and low non-HDL levels (p value < 0.05). When considered collectively, the findings of this study are consistent with the hypothesis that the DD genotype of ACE polymorphism represents a correlation with cardiovascular disease risk factors in this population.

Deep Phosphoproteome Landscape of Interhemispheric Functionality of Neuroanatomical Regions of the Human Brain.

Post-translational modifications (PTMs) are one of the compulsive and predominant biological processes that regulate the diverse molecular mechanism, modulate the onset of disease, and are the reason behind the functional diversity of proteins. Despite the widespread research findings in neuroproteomics, one of the key drawbacks has been the lack of proteome-level knowledge of hemispheric lateralization. We have investigated the proteome level expression in different neuroanatomical regions under the Human Brain Proteome Project (HBPP) and developed the global interhemispheric brain proteome map (Brainprot) earlier. Furthermore, this study has extended to decipher the phosphoproteome map of human brain interhemispheric regions through high-resolution mass spectrometry. The phosphoproteomics examination of 12 unique interhemispheric neurological brain regions using Orbitrap fusion liquid chromatography with tandem mass spectrometry provided comprehensive coverage of 996 phosphoproteins, 2010 phosphopeptides, and 3567 phosphosites. Moreover, interhemispheric phosphoproteome profiling has been categorized according to synaptic ontologies and interhemispheric expression to understand the functionality. Finally, we have integrated the phosphosites data under the PhosphoMap section in the Inter-Hemispheric Brain Proteome Map Portal (https://www.brainprot.org/) for the advancement and support of the ongoing neuroproteomics research worldwide. Data is available via ProteomeXchange with the identifier PXD031188.

Oxidative Stress-induced Autophagy Compromises Stem Cell Viability.

Stem cell therapies have emerged as a promising treatment strategy for various diseases characterized by ischemic injury such as ischemic stroke. Cell survival after transplantation remains a critical issue. We investigated the impact of oxidative stress, being typically present in ischemically challenged tissue, on human dental pulp stem cells (hDPSC) and human mesenchymal stem cells (hMSC). We used oxygen-glucose deprivation (OGD) to induce oxidative stress in hDPSC and hMSC. OGD-induced generation of O2•- or H2O2 enhanced autophagy by inducing the expression of activating molecule in BECN1-regulated autophagy protein 1 (Ambra1) and Beclin1 in both cell types. However, hDPSC and hMSC pre-conditioning using reactive oxygen species (ROS) scavengers significantly repressed the expression of Ambra1 and Beclin1 and inactivated autophagy. O2•- or H2O2 acted upstream of autophagy, and the mechanism was unidirectional. Furthermore, our findings revealed ROS-p38-Erk1/2 involvement. Pre-treatment with selective inhibitors of p38 and Erk1/2 pathways (SB202190 and PD98059) reversed OGD effects on the expression of Ambra1 and Beclin1, suggesting that these pathways induced oxidative stress-mediated autophagy. SIRT3 depletion was found to be associated with increased oxidative stress and activation of p38 and Erk1/2 MAPKs pathways. Global ROS inhibition by NAC or a combination of polyethylene glycol-superoxide dismutase (PEG-SOD) and polyethylene glycol-catalase (PEG-catalase) further confirmed that O2•- or H2O2 or a combination of both impacts stems cell viability by inducing autophagy. Furthermore, autophagy inhibition by 3-methyladenine (3-MA) significantly improved hDPSC viability. These findings contribute to a better understanding of post-transplantation hDPSC and hMSC death and may deduce strategies to minimize therapeutic cell loss under oxidative stress.

Oral Delivery of Nucleic Acid Therapies for Local and Systemic Action.

Nucleic acid (NA) therapy has gained importance over the past decade due to its high degree of selectivity and minimal toxic effects over conventional drugs. Currently, intravenous (IV) or intramuscular (IM) formulations constitute majority of the marketed formulations containing nucleic acids. However, oral administration is traditionally preferred due to ease of administration as well as higher patient compliance. To leverage the benefits of oral delivery for NA therapy, the NA of interest must be delivered to the target site avoiding all degrading and inhibiting factors during its transition through the gastrointestinal tract. The oral route presents myriad of challenges to NA delivery, making formulation development challenging. Researchers in the last few decades have formulated various delivery systems to overcome such challenges and several reviews summarize and discuss these strategies in detail. However, there is a need to differentiate between the approaches based on target so that in future, delivery strategies can be developed according to the goal of the study and for efficient delivery to the desired site. The goal of this review is to summarize the mechanisms for target specific delivery, list and discuss the formulation strategies used for oral delivery of NA therapies and delineate the similarities and differences between local and systemic targeting oral delivery systems and current challenges.

Schiff Bases: A Versatile Fluorescence Probe in Sensing Cations.

Metal cations such as Zn2+, Al3+, Hg2+, Cd2+, Sn2+, Fe2+, Fe3+ and Cu2+ play important roles in biology, medicine, and the environment. However, when these are not maintained in proper concentration, they can be lethal to life. Therefore, selective sensing of metal cations is of great importance in understanding various metabolic processes, disease diagnosis, checking the purity of environmental samples, and detecting toxic analytes. Schiff base probes have been largely used in designing fluorescent sensors for sensing metal ions because of their easy processing, availability, fast response time, and low detection limit. Herein, an in-depth report on metal ions recognition by some Schiff base fluorescent sensors, their sensing mechanism, their practical applicability in cell imaging, building logic gates, and analysis of real-life samples has been presented. The metal ions having biological, industrial, and environmental significance are targeted. The compiled information is expected to prove beneficial in designing and synthesis of the related Schiff base fluorescent sensors.

Comparative proteomic investigation unravels the pathobiology of Mycobacterium fortuitum biofilm.

Biofilm formation by Mycobacterium fortuitum causes serious threats to human health due to its increased contribution to nosocomial infections. In this study, the first comprehensive global proteome analysis of M. fortuitum was reported under planktonic and biofilm growth states. A label-free Q Exactive Quadrupole-Orbitrap tandem mass spectrometry analysis was performed on the protein lysates. The differentially abundant proteins were functionally characterized and re-annotated using Blast2GO and CELLO2GO. Comparative analysis of the proteins among two growth states provided insights into the phenotypic switch, and fundamental pathways associated with pathobiology of M. fortuitum biofilm, such as lipid biosynthesis and quorum-sensing. Interaction network generated by the STRING database revealed associations between proteins that endure M. fortuitum during biofilm growth state. Hypothetical proteins were also studied to determine their functional alliance with the biofilm phenotype. CARD, VFDB, and PATRIC analysis further showed that the proteins upregulated in M. fortuitum biofilm exhibited antibiotic resistance, pathogenesis, and virulence. Heatmap and correlation analysis provided the biomarkers associated with the planktonic and biofilm growth of M. fortuitum. Proteome data was validated by qPCR analysis. Overall, the study provides insights into previously unexplored biochemical pathways that can be targeted by novel inhibitors, either for shortened treatment duration or for eliminating biofilm of M. fortuitum and related nontuberculous mycobacterial pathogens. KEY POINTS: • Proteomic analyses of M. fortuitum reveals novel biofilm markers. • Acetyl-CoA acetyltransferase acts as the phenotype transition switch. • The study offers drug targets to combat M. fortuitum biofilm infections.

The Effect of Cadmium Tolerant Plant Growth Promoting Rhizobacteria on Plant Growth Promotion and Phytoremediation: A Review.

Cadmium (Cd) is a heavy metal of considerable toxicity with destructive impacts on plants, microbes and environments. Its toxicity is due to mishandling and manual hazards in plants and is primarily observed within the soil to cause decline of plants and microbial activity inside the rhizosphere. Cadmium accumulation in crops and the probability of Cd entering the food chain are grave for public health in the worldwide. Cadmium toxicity leads to depletion in seed germination, initial seedling growth, plant biomass, chlorosis, necrosis, hindrance of photosynthetic machinery and other physiological and biological activities in plants. Cadmium triggers the reactive oxygen species (ROS) that influences gene mutation and DNA damage that affects the cell cycle and cell division. Cd toxicity altered the levels of phenolic compounds, carbohydrates, glycine betaine, proline and organic acids in crops. Under stress conditions, the plant growth promoting rhizobacteria (PGPR) have various properties such as enzymatic activities, plant growth hormones production, phosphate solubilization, siderophores production and chelating agents that help the plants tolerate against Cd stress and also increase phenolic compound levels and osmolytes. Hence, this review highlights the crucial role of cadmium tolerant PGPR for crop production, declining metal phytoavailability and enhancing morphological and physiological boundaries of plants under stress conditions. It could be an environment friendly and cost effective technology under sustainable crop production.

Enhanced photocatalytic activity of ceria-doped zinc oxide under UV illumination prepared via chemical precipitation.

Transition metal oxide has emerged as one of the most potential candidates for environment remediation by utilizing solar energy through photocatalysis. This study compares the optical characteristics of zinc oxide (ZnO) and ceria-doped zinc oxide (CeZnO) nanoparticles synthesized through a facile chemical precipitation method without using any assistant catalyst. The present work investigates the consequences of ceria (cerium dioxide, CeO2 ) intrusion on the photocatalytic activity of ZnO nanoparticles using methylene blue (MB) as a probe pollutant. The CeZnO showed an increase in photoactivity when compared to ZnO nanoparticles for degradation of MB in an aqueous solution under ultraviolet (UV) irradiance. The resulting heterojunction between ZnO and that of ceria enhances the charge separation efficiency showing a strong correlation between ZnO and CeO2 heterojunction on the charge transfer mechanism across the interface.

Resilience and Mitigation Strategies of Cyanobacteria under Ultraviolet Radiation Stress.

Ultraviolet radiation (UVR) tends to damage key cellular machinery. Cells may adapt by developing several defence mechanisms as a response to such damage; otherwise, their destiny is cell death. Since cyanobacteria are primary biotic components and also important biomass producers, any drastic effects caused by UVR may imbalance the entire ecosystem. Cyanobacteria are exposed to UVR in their natural habitats. This exposure can cause oxidative stress which affects cellular morphology and vital processes such as cell growth and differentiation, pigmentation, photosynthesis, nitrogen metabolism, and enzyme activity, as well as alterations in the native structure of biomolecules such as proteins and DNA. The high resilience and several mitigation strategies adopted by a cyanobacterial community in the face of UV stress are attributed to the activation of several photo/dark repair mechanisms, avoidance, scavenging, screening, antioxidant systems, and the biosynthesis of UV photoprotectants, such as mycosporine-like amino acids (MAAs), scytonemin (Scy), carotenoids, and polyamines. This knowledge can be used to develop new strategies for protecting other organisms from the harmful effects of UVR. The review critically reports the latest updates on various resilience and defence mechanisms employed by cyanobacteria to withstand UV-stressed environments. In addition, recent developments in the field of the molecular biology of UV-absorbing compounds such as mycosporine-like amino acids and scytonemin and the possible role of programmed cell death, signal perception, and transduction under UVR stress are discussed.

Chemo-/Regio-Selective Synthesis of Novel Functionalized Spiro[pyrrolidine-2,3'-oxindoles] under Microwave Irradiation and Their Anticancer Activity.

A novel series of nitrostyrene-based spirooxindoles were synthesized via the reaction of substituted isatins 1a-b, a number of α-amino acids 2a-e and (E)-2-aryl-1-nitroethenes 3a-e in a chemo/regio-selective manner using [3+2] cycloaddition (Huisgen) reaction under microwave irradiation conditions. The structure elucidation of all the synthesized spirooxindoles were done using 1H and 13C NMR and HRMS spectral analysis. The single crystal X-ray crystallographic study of compound 4l was used to assign the stereochemical arrangements of the groups around the pyrrolidine ring in spiro[pyrrolidine-2,3'-oxindoles] skeleton. The in vitro anticancer activity of spiro[pyrrolidine-2,3'-oxindoles] analogs 4a-w against human lung (A549) and liver (HepG2) cancer cell lines along with immortalized normal lung (BEAS-2B) and liver (LO2) cell lines shows promising results. Out of the 23 synthesized spiro[pyrrolidine-2,3'-oxindoles], while five compounds (4c, 4f, 4m, 4q, 4t) (IC50 = 34.99-47.92 µM; SI = 0.96-2.43) displayed significant in vitro anticancer activity against human lung (A549) cancer cell lines, six compounds (4c, 4f, 4k, 4m, 4q, 4t) (IC50 = 41.56-86.53 µM; SI = 0.49-0.99) displayed promising in vitro anticancer activity against human liver (HepG2) cancer cell lines. In the case of lung (A549) cancer cell lines, these compounds were recognized to be more efficient and selective than standard reference artemisinin (IC50 = 100 µM) and chloroquine (IC50 = 100 µM; SI: 0.03). However, none of them were found to be active as compared to artesunic acid [IC50 = 9.85 µM; SI = 0.76 against lung (A549) cancer cell line and IC50 = 4.09 µM; SI = 2.01 against liver (HepG2) cancer cell line].

Correction: Pd-Catalysed [3 + 2]-cycloaddition towards the generation of bioactive bis-heterocycles/identification of COX-2 inhibitors via in silico analysis.

Correction for 'Pd-Catalysed [3 + 2]-cycloaddition towards the generation of bioactive bis-heterocycles/identification of COX-2 inhibitors via in silico analysis' by Elagandhula Sathish et al., Org. Biomol. Chem., 2022, 20, 4746-4752, https://doi.org/10.1039/D2OB00467D.

Pd-Catalysed [3 + 2]-cycloaddition towards the generation of bioactive bis-heterocycles/identification of COX-2 inhibitors via in silico analysis.

In the current research, we envisaged the synthesis of bis-heterocycles containing the dihydroisoxazole ring by [3 + 2] cycloaddition of VECs (vinyl ethylene carbonates) and nitrile oxides, assisted by a Pd catalyst. Herein we explored hydroximoyl chlorides as versatile precursors for the in situ generation of nitrile oxides that were exploited to achieve the cycloaddition reaction on a vinyl group of VECs to generate bis-heterocycles. In silico-based studies of bis-heterocycles on the cyclooxygenase (COX) enzyme displayed selective COX-2 inhibition.

Synthesis and anti-HIV activity of a new isoxazole containing disubstituted 1,2,4-oxadiazoles analogs.

Continuing on our antiviral drug discovery research, we intended to diversify our lead anti-HIV-1 inhibitor by non-classical isosteric replacement of amide to 1,2,4-oxadiazoles. The resulting molecules isoxazole-1,2,4-oxadiazole analogs were synthesized using mild bases in ethanol under microwave irradiation. The anti-HIV potential was checked in human CD4+ reporter cell lines, TZM-bl and CEM-GFP, at the highest non-cytotoxic concentration (HNC), demonstrating that 3-((3-(p-tolyl)isoxazol-5-yl)methyl)-1,2,4-oxadiazole and 3-((3-(4-chlorophenyl)isoxazol-5-yl)methyl)-1,2,4-oxadiazole inhibit HIV-1 replication significantly and could be considered as a new lead candidate against HIV-1.

COMPARATIVE EVALUATION OF OUTCOMES OF DRAINAGE TECHNIQUES IN VITRECTOMY FOR RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To compare the anatomical and functional outcomes of drainage through posterior retinotomy versus perfluorocarbon liquid (PFCL)-assisted drainage in vitreoretinal surgery for rhegmatogenous retinal detachment and to study intraoperative and postoperative complications. METHODS: This was a prospective randomized study of 52 cases who underwent vitreoretinal surgery for rhegmatogenous retinal detachment. Group 1 underwent PFCL-assisted drainage through preexisting break, whereas Group 2 had posterior retinotomy to drain subretinal fluid. Cases were evaluated for retinal reattachment rates, visual outcomes, optical coherence tomography parameters, and postoperative metamorphopsia. The patients were followed up for minimum period of 3 months. RESULTS: Two groups were comparable in terms of demographic and preoperative parameters. Both groups had single surgery success rate of 100% by the end of follow-up. Final best-corrected visual acuity in Group 1 was 0.61 ± 0.33 and 0.61 ± 0.32 in Group 2 (P = 0.77). Optical coherence tomography parameters (foveal contour, retinal layers, central macular thickness, and epiretinal membrane formation) were similar between the two groups. Subjective metamorphopsia was present in 30.77% (8 of 26) patients in Group-1 and 69.23% (18 of 26) patients in Group-2 (P = 0.034). One eye had retained subretinal PFCL away from the macula in Group 1. CONCLUSION: Anatomical and functional outcomes were similar in vitrectomy using PFCL-assisted drainage versus posterior retinotomy drainage. Postoperative metamorphopsia was lesser in patients who underwent PFCL-assisted drainage through the pre-existing break.

Prevalence of Pulmonary Hypertension in Chronic Kidney Disease.

Pulmonary hypertension is a common comorbidity in patients with chronic kidney disease and end-stage renal disease(CKD). The presence of pulmonary hypertension is associated with increased risk of hospitalization and mortality in patients with CKD. Review of literature showed that in one study, pulmonary hypertension was found in 40% of patients with end stage renal disease on chronic hemodialysis therapy via arteriovenous access. The presence of CKD was associated with 1.4-fold increased risk of having pulmonary hypertension after adjusting for other independent risk factors for CKD. Preventing pulmonary hypertension in this population is crucial because even kidney transplantation may not reverse the high mortality associated with established pulmonary hypertension. MATERIAL: Place of study- Rajendra Institute of Medical Sciences, Ranchi. Design of study- Observational and prospective single centered study. Duration of study-18 months. Sample size-100 CKD patients admitted to department of medicine, RIMS, Ranchi. Study population-100 CKD patients meeting our inclusion criteria, admitted in the department of medicine, Rajendra Institute of Medical Sciences, Ranchi, between 1st January 2020 and 30th June 2021. INCLUSION CRITERIA: Renal function was determined by estimated glomerular filtration rate. Only patients with stage 3 or worse CKD were included. EXCLUSION CRITERIA: 1. Those patients having stage 2 or less kidney disease were excluded. 2. Patients with congenital heart disease, chronic thromboembolic disease, acute myocardial infarction and previous lung disease or cardiac transplantation were excluded. Data was collected by oral questionnaire, relevant investigations and by doing 2D- ECHO and data was analyzed by using IBM SPSS Statistics software. OBSERVATION: Prevalence of pulmonary hypertension in the study group was 16%. Prevalence of pulmonary hypertension was more in stage 5 CKD patients (26.19%) and the difference in prevalence of pulmonary hypertension in different stages of CKD was statistically significant(p value-0.008). Prevalence of pulmonary hypertension was more in patients on hemodialysis (27.78%) compared to those not on hemodialysis (9.37%). Pulmonary hypertension was present in 13.85% males and 20% of females, there was no statistically significant difference (p value-.428). No significant difference was found in prevalence of pulmonary hypertension between diabetic and non- diabetic patients and hypertensive and normotensive patients. CONCLUSION: Prevalence of pulmonary hypertension was more in stage 5 CKD patients and patients on hemodialysis. There was positive correlation between high serum creatinine, high serum phosphorus, lower hemoglobin, lower serum calcium and pulmonary hypertension in CKD patients. There was no significant difference in prevalence of pulmonary hypertension in male and female patients.

Evaluation of the Antimicrobial Activity of Magnetized Water and Its Comparison with Chlorhexidine 0.2% in Young Children for 3 Weeks.

AIM: The goal of this study was to compare the effects of magnetized water and 0.2% chlorhexidine mouthwash on gingivitis and plaque prevention in children aged 12-15 years for a period of 21 days. MATERIALS AND METHODS: A total of 24 youngsters between the ages of 12 and 15 years were chosen. A computer-generated random number sequence was used to split the research participants into two groups. Magnetized water was utilized as a mouthrinse in Category 1, while 0.2% chlorhexidine was employed in Category 2. Water purified with reverse osmosis was stored in glass bottles, which were then put near the magnets to create magnetic water. The magnets had 1000 Gauss power. The bottles were put for a period of 24 hours. The youngsters were given 140 mL of mouthrinse. These mouthrinses were to be used at home, they were told. The Gilmore Turesky adaptation of Quigley Hein's plaque index was used to assess the plaque whereas the gingival index recommended by Loe and Sillness was utilized to assess the gingiva. The plaque index and gingival index were analyzed at baseline, 14 days, and 21 days, as well as history and examination for adverse effects such as bitter taste, brownish discoloration, and so on, were recorded. The trial lasted 21 days with a follow-up period of another 21 days. RESULTS: Both magnetic water and chlorhexidine were similarly successful in managing periodontal and gingival infections; however, magnetized water had less side effects, such as a bitter metallic taste and brown stains. CONCLUSION: Because of its well-accepted flavor, softer nature, and lower frequency of brown stains, magnetized water can be a safer and more acceptable alternative to chlorhexidine mouthwashes, especially in youngsters. CLINICAL SIGNIFICANCE: The use of chlorhexidine as a mouthrinse in the oral cavity has been linked to side effects. These side effects are mostly localized, such as brownish discoloration of teeth, alterations in taste perception, and erosion of the oral mucosa. As chlorhexidine has such negative side effects, it was necessary to do research, particularly in children, to identify a replacement that is similarly efficient against germs but does not have these side effects. Water treated with a magnetic field (magnetized water) was compared with chlorhexidine in the current study.

Mining the Mycobacterium tuberculosis proteome for identification of potential T-cell epitope based vaccine candidates.

Identification of protective antigens for designing a high-efficacy tuberculosis vaccine is the need of the hour. Till date only 7% of the Mycobacterium tuberculosis proteome has been explored for discovering antigens capable of activating T-cell responses. Therefore, it becomes crucial to screen the remaining Mycobacterium tuberculosis proteome for more immunodominant T-cell epitopes. An extensive knowledge of the epitopes recognized by our immune system can aid this process of finding potential T cell antigens for development of a better TB vaccine. In the present in-silico study, 237 proteins belonging to the 'virulence, detoxification, and adaptation' category of Mycobacterium tuberculosis proteome were targeted for T-cell epitope screening. 50825 MHC Class I and 49357 MHC Class II epitopes were generated using NetMHC3.4 and IEDB servers respectively and tested for their antigenicity and cytokine stimulation. The highest antigenic epitopes were analyzed for their world population coverage and epitope conservancy. Molecular docking and molecular dynamics simulation studies were performed to corroborate the binding affinities and structural stability of the peptide-MHC complexes. We predicted a total of 3 MHC Class I (ILLKMCWPA, FAVGMNVYV, and SLAGNSAKV) and 7 MHC Class II (DLTIGFFLHIPFPPV, RPDLTIGFFLHIPFP, LTIGFFLHIPFPPVE, VLVFALVVALVYLQF, LVFALVVALVYLQFR, PNLVAARFIQLTPVY, and LVLVFALVVALVYLQ) epitopes that can be promising vaccine candidates. These predicted epitopes belong to 6 distinct proteins: Rv0169 (mce1a), Rv3490 (ostA), Rv3496 (mce4D), Rv1085c, Rv0563 (HtpX), Rv3497c (mce4C). All these proteins are expressed at different stages in the life cycle of Mycobacterium tuberculosis and thus, the predicted epitopes could be employed as candidates for designing a multistage-multiepitopic vaccine.

Production and characterization of a novel, thermotolerant fungal phytase from agro-industrial byproducts for cattle feed.

OBJECTIVE: The application of phytases helps in releasing bound phosphorus and other nutrients in cattle feed eventually reducing the need for supplementations. However, high production cost owing to the unavailability of cheaper sources of phytases has limited their usage in developing countries. Herein, firstly isolation, identification of a phytase from fungal isolate, Aspergillus niger NT7 was carried out followed by optimizing of all production parameters, through solid-state fermentation (SSF). Secondly, crude phytase was characterized and potential applicability of crude phytase was evaluated for dephytinization of wheat bran. RESULTS: The highest phytase production (208.30 ± 0.22 U/gds) was achieved using wheat bran as cheap agro-industrial substrate for SSF. The various physiological parameters were optimized including inoculum age and level (3-day old inoculum and 15 × 107 spores/ml), temperature (35 °C), a moistening agent (distilled water), medium pH (5), and supplementation of various biochemicals like sugar (Mannitol), nitrogen (ammonium sulphate) and detergent (Tween 80). Process optimization through one variable at a time (OVAT) approach increased the difference in productivity to more than 200%. The crude phytase of A. niger NT7 was thermostable, with optimal activity at 60 °C and also displayed optimal activity over a broad range of acidic pH. Further, enhancement in phytase activity was found specifically in the presence of Ca2+, Zn2+, and Co2+ ions, while other metal ions including Fe2+, Fe3+, Mn2+, Mg2+and Cu2+ inhibited its activity. Finally, the phytase showed efficient and sustained release of inorganic phosphate, proteins, and reducing sugars (> 60 h) from livestock feed. CONCLUSION: Overall, our report highlights the production of an efficient and thermotolerant phytase with potential as a low-cost animal feed supplement.