Exploring Tryptophan-based Short Peptides: Promising Candidate for Anticancer and Antimicrobial Therapies.

BACKGROUND: Ultra-short peptides are essential therapeutic agents due to their heightened selectivity and reduced toxicity. Scientific literature documents the utilization of dipeptides, tripeptides, and tetrapeptides as promising agents for combating cancer. We have created a range of tryptophan-based peptides derived from literature sources in order to assess their potential as anticancer drugs. METHODS: We present the results of our study on the antibacterial and anticancer effectiveness of 10 ultra-short peptides that were produced utilizing microwave-assisted solid phase peptide synthesis. The synthesized peptides underwent screening for in vitro antibacterial activity using the agar dilution method. RESULTS: HPLC, LC-MS, 1H NMR, and 13C NMR spectroscopy were used to analyze the synthesized peptides. In tests using the HeLa and MCF-7 cell lines, the synthesized peptides' anticancer efficacy was assessed. The study found that two peptides showed potential median inhibitory concentration (IC50) values of 3.9±0.13 µM and 1.8±0.09 µM, respectively, and showed more activity than the reference medication doxorubicin. CONCLUSION: The antibacterial activity of synthesized peptides 3b and 4b was found to be better than the other synthetic peptides. MIC value of roughly 5-50 µg/mL for peptides 3a, 4c, and 4d showed strong antifungal activity against Candida albicans. The synthesized peptides were also evaluated for their anticancer activity against HeLa and MCF-7 cell lines, and found that peptides 3e and 4e were more potent than other peptides against doxorubicin.

Whole-body exposure to filtered fraction of diesel exhaust induced localized testicular damage through attenuated functional response of glutathione-s-transferase in adult male Wistar rats.

The possible vulnerability of the male reproductive system to environmental pollutants such as air pollution necessitates a thorough investigation of the underlying mechanisms involved in the dysregulation of male reproductive function. The present study was designed to investigate the influence of the filtered fraction of diesel exhaust (predominantly comprising gases) on male reproductive function in Wistar rat model. Adult male rats were randomly assigned into three groups (n=8/group): Control (unexposed) group (CG-A), the Clean air group in WBE chamber (CAG-A), and Filtered diesel exhaust group in WBE chamber (FDG-A). The exposure protocol for CAG-A and FDG-A was 6 h/day x 5d/week x 6 weeks,evaluation of sperm parameters, testicular histopathology, quantification of hormones (testosterone, LH, FSH, 17ß-Estradiol, and prolactin), and GST levels were performed. Results showed that WBE to FDE leads to a significant decline in sperm concentration (p=0.008, CG-A vs FDG-A; p=0.014, CAG-A vs FDG-A), motility (p=0.008, CG-A vs FDG-A; p=0.029, CAG-A vs FDG-A), serum testosterone (p=0.024, CG-A vs FDG-A; p=0.007, CAG-A vs FDG-A), testicular testosterone (p=0.008, CG-A vs FDG-A; p=0.028, CAG-A vs FDG-A), 17ß-Estradiol (p=0.007, CG-A vs FDG-A), and GST levels (p=0.0002, CG-A vs FDG-A; p=0.0019, CAG-A vs FDG-A). These findings demonstrate the disruption of testosterone-estradiol balance in the intratesticular milieu without significant alterations in other principal pituitary hormones in adult rats exposed to FDE. The predominant presence of gaseous components in FDE can cause testicular damage due to oxidative imbalance. This underscores the causality of FDE exposure and impaired male reproductive outcomes.

Enteroviruses Associated with Hand Foot and Mouth Disease in Navi Mumbai, Maharashtra, India in 2022.

An outbreak of Hand Foot and Mouth Disease (HFMD) which occurred in August-September, 2022 in Navi Mumbai, India was prospectively investigated, to delineate the clinical manifestations and identify the etiological agent. Molecular characterization at ICMR-National Institute of Virology (NIV), Mumbai unit reported 69 (88.5%) cases out of 78 clinically diagnosed HFMD cases positive for enteroviruses. Thirty-nine (56.5%) children were positive for CVA6, 11 (15.9%) for CVA16, and one for CVA4 (1.4%). One case of co-infection (CVA16, CVA6) was reported. Fourteen (17.9%) cases had recurrent disease in the same season. CVA6 was associated with unusual extension of the rash beyond the conventional areas of hands, feet, and mouth, with involvement of body areas including face, axillae and trunk. Whole genome sequencing classified CVA6 as group D3 and CVA16 isolates as group B1c. Co-infection and recurrence of disease with atypical symptoms observed in this study highlight the need for continued vigilance of the evolutionary clinical characteristics of the enteroviruses causing HFMD.

Comparative evaluation of GSH, total protein and albumin levels in patients using smokeless tobacco with oral precancerous and cancerous lesions.

Smokeless tobacco (SLT) causes the excessive production of reactive oxygen species, leading to oxidative damage and carcinogenesis. The present study aimed to evaluate the levels of biomarkers, such as glutathione (GSH) in the blood, as well as serum albumin and total protein levels in SLT users with oral precancerous and cancerous lesions. A cross-sectional, prospective study was conducted on 240 patients aged 30-60 years, divided into four groups with 60 patients in each group as follows: Group 1, control group, non-tobacco users; group 2, 60 subjects with a history of SLT use and no oral lesions; group 3, SLT users with precancerous oral lesions; and group 4, SLT users with cancerous lesions. GSH levels in the blood, serum albumin levels and total protein levels were evaluated in all groups. ANOVA and Tukey's test post hoc were used to compare the levels of the biomarkers in all groups. Receiver operating characteristic curves were used to assess the reliability of the biomarkers, and regression analysis was used to determine the associations between the variables. The use of SLT was predominantly observed in males. The mean GSH and serum albumin levels were lowest in group 4 and highest in the control group (P<0.001). The total serum protein levels were higher in group 4 than in group 3. On the whole, as demonstrated herein, GSH and serum albumin were reliable biomarkers, whereas total protein was a weak biomarker. GSH and serum albumin levels may thus be efficiently used for the early diagnosis and prognosis of oral malignancies in SLT users.

Subacute Exposure to Gaseous Pollutants from Diesel Engine Exhaust Attenuates Capsaicin-Induced Cardio-Pulmonary Reflex Responses Involving Oxidant Stress Mechanisms in Adult Wistar Rats.

Intravenous injection of capsaicin produces vagal-mediated protective cardio-pulmonary (CP) reflexes manifesting as tachypnea, bradycardia, and triphasic blood pressure (BP) response in anesthetized rats. Particulate matter from diesel engine exhaust has been reported to attenuate these reflexes. However, the effects of gaseous constituents of diesel exhaust are not known. Therefore, the present study was designed to investigate the effects of gaseous pollutants in diesel exhaust, on capsaicin-induced CP reflexes in rat model. Adult male rats were randomly assigned to three groups: Non-exposed (NE) group, filtered diesel exhaust-exposed (FDE) group and N-acetyl cysteine (NAC)-treated FDE group. FDE group of rats (n = 6) were exposed to filtered diesel exhaust for 5 h a day for 5 days (D1-D5), and were taken for dissection on day 6 (D6), while NE group of rats (n = 6) remained unexposed. On D6, rats were anesthetized, following which jugular vein was cannulated for injection of chemicals, and femoral artery was cannulated to record the BP. Lead II electrocardiogram and respiratory movements were also recorded. Results show that intravenous injection of capsaicin (0.1 ml; 10 µg/kg) produced immediate tachypneic, hyperventilatory, hypotensive, and bradycardiac responses in both NE and FDE groups of rats. However, these capsaicin-induced CP responses were significantly attenuated in FDE group as compared to the NE group of rats. Further, FDE-induced attenuation of capsaicin-evoked CP responses were diminished in the N-acetyl cysteine-treated FDE rats. These findings demonstrate that oxidant stress mechanisms could possibly be involved in inhibition of CP reflexes by gaseous pollutants in diesel engine exhaust.

Comparative Analysis of Dentition and Periodontal Status in Patients With Unilateral Smokeless Tobacco Pouch Keratosis.

INTRODUCTION: The consumption of smokeless tobacco (SLT) and related products has become an epidemic worldwide, especially among young people, as they come into direct contact with the tissues of the oral cavity. Therefore, the present cross-sectional study was conducted to compare the status of dentition and periodontal health of teeth associated with the unilateral SLT pouch keratosis with the unaffected contralateral side. MATERIALS AND METHODS: In this study, 96 SLT users from north Maharashtra, India, with unilateral SLT pouch keratosis were studied. Demographic data, past and present SLT use history, features of SLT pouch keratosis, modified community periodontal index, dentition status index, and loss of tooth attachment were recorded. Data were collected and subjected to statistical analysis using the unpaired t-test and chi-square test. RESULTS: The results of the present study showed a significant difference (p≤0.05) in gingival bleeding, pocket depth, and attachment loss in teeth associated with smokeless tobacco keratosis (STK) compared to teeth at the contralateral sides of the arch. The duration of tobacco use had a significant effect on the severity of loss of attachment at SLT pouch keratosis sides. There was a significant difference (p≤0.05) in the mean scores of the sound crown, carious crown, and coronal caries status between the SLT pouch keratosis side and the contralateral side. CONCLUSION: The results of the study revealed that significant gingival bleeding, gingival recession, and attachment loss in the teeth are associated with SLT pouch keratosis compared with the teeth on the contralateral side without the lesion.

One for Everyone: A Study of User Satisfaction Among Health-Care Providers Regarding Extended Use of N95 Masks During the COVID-19 Pandemic.

OBJECTIVE: This study was conducted to assess the feasibility of extended use of N95 masks in our hospital during the coronavirus disease 2019 (COVID-19) pandemic. We also studied the use pattern, user satisfaction, and issues faced during extended use of the mask. METHODS: This cross-sectional study was conducted among health-care providers in a large tertiary care teaching hospital in northern India from April 1 to May 31, 2020. A list was prepared from the institute's register, and participants were chosen by random sampling. The data collected from the physical forms were transferred to excel sheets. RESULTS: A total of 1121 responses were received. The most common problem stated with reuse of N95 masks was loss of fit followed by damage to the slings, highlighted by 44.6% and 44.4% of the participants, respectively. A total of 476 (42.5%) participants responded that they would prefer "cup-shaped N95 mask with respirator". The median scores regarding the satisfaction with the quality of masks and their fit was also 4 each. CONCLUSIONS: It was concluded that the extended use of N95 masks was acceptable, with more than 96% of the participants using these masks.

Current Discovery Progress of Some Emerging Anti-infective Chalcones: Highlights from 2016 to 2017.

The anti-infective potentials of the natural products are very well known for centuries and are a part of traditional healing. The foremost therapeutic classes include flavones, isoflavones, flavonols, flavanones, flavanols, proanthocyanidins, anthocyanidins, chalcones, and aurones. The chalcone or 1,3-diphenyl-2E-propene-1-one represents the class of natural products which are comprised of benzylideneacetophenone function; i.e. two aromatic moieties linked together by an α, ß-unsaturated carbonyl bridge comprising three-carbons. At present, chalcone is one of the privileged scaffolds that can be synthesized in the laboratory to derive different pharmacologically active compounds. This article is the continued form of the previously published work on anti-infective perspectives of chalcones (highlighted till 2015). The current work emphasizes on the discovery process of the chalcone in the period of 2016 to 2017 on malaria, trypanosomiasis, leishmaniasis, filaria, tuberculosis, netamodes, Human Immunodeficiency Virus (HIV), Tobacco Mosaic Virus (TMV), Severe Acute Respiratory Syndrome (SARS), and miscellaneous conditions. This review comprehensively focuses on the latest progress related with the anti-infective chalcones. The content includes the crucial structural features of chalcone scaffold including structure-activity relationship(s) along with their plausible mechanism of action(s) from the duration Jan 2016 to Dec 2017. This literature will be of prime interest to medicinal chemists in getting ideas and concepts for better rational development of potential anti-infective inhibitors.

Development of a self-assessment tool for resident doctors' communication skills in India

PURPOSE: Effective communication skills are essential for resident doctors to provide optimum patient care. This study was conducted to develop and validate a questionnaire for the self-assessment of resident doctors' communication skills in India. METHODS: This was a mixed-methods study conducted in 2 phases. The first phase consisted of questionnaire development, including the identification of relevant literature, focus group discussions with residents and experts from clinical specialties, and pre-testing of the questionnaire. The second phase involved administering the questionnaire survey to 95 residents from the Departments of Medicine, Emergency Medicine, Pediatrics, and Surgery at the All India Institute of Medical Sciences, New Delhi, India in April 2019. Internal consistency was tested and the factor structure was analyzed to test construct validity. RESULTS: The questionnaire consisted of 3 sections: (A) 4 items on doctor-patient conflicts and the role of communication skills in avoiding these conflicts, (B) 29 items on self-assessment of communication skills in different settings, and (C) 8 items on barriers to practicing good communication skills. Sections B and C had good internal consistency (Cronbach α: 0.885 and 0.771, respectively). Section C had a 2-factor solution, and the barriers were classified as 'training' and 'infrastructure' factors. CONCLUSION: This appears to be a valid assessment tool of resident doctors' communication skills, with potential utility for identifying gaps in communication skills and developing communication skills modules.

Whole genome shotgun sequences of Streptococcus pyogenes causing acute pharyngitis from India.

Streptococcus pyogenes, belonging to group A streptococcus (GAS), causes over 600 million infections annually being a predominant human pathogen. Lack of genomic data on GAS from India is one limitation to understand its virulence and antimicrobial resistance determinants. The genome of GAS isolates from clinical samples collected at Navi Mumbai, India was sequenced and annotated. Sequencing was performed on Ion Torrent PGM platform. The size of annotated S. pyogenes genomes ranged from ~1.69 to ~1.85 Mb with coverage of 38× to 189×. Most of the isolates had msr(D) and mef(A), and four isolates had erm(B) gene for macrolide resistance. The genome harboured multiple virulence factors including exotoxins in addition to phage elements in all GAS genomes. Four isolates belonged to sequence type ST28, 7 were identified as ST36 and 1 as ST55.

Students' perception of the educational environment in medical college: a study based on DREEM questionnaire.

PURPOSE: The educational environment (EE) plays a very important role in effective student learning. The Dundee Ready Education Environment Measure (DREEM) is a validated tool to assess the EE. This study aimed to collect baseline information about our medical student's perception of the EE, and to identify areas of strengths and weaknesses as well as scope for improvements in the current EE. METHODS: Medical students and interns were included in this cross-sectional study. The DREEM questionnaire was used to measure students' perceptions about the EE, which has five domains: students' perceptions of learning; students' perceptions of teachers; students' academic self-perceptions; students' perceptions of atmosphere; and students' social self-perceptions. Students were asked to respond using a 5-point Likert-type scale. Data was analyzed using suitable tests and statistical significance was set at p<0.05. RESULTS: The mean global DREEM score was 123/200. All students had more positive than negative academic self-perception (21.24/32), perception of atmosphere (29.21/48), and perception of learning (28.99/48), while their social self-perception (17.48/28) was not too bad and perception of teachers (26.71/44) moved in the right direction. The fifth semester students perceived EE more positively than other semester students. CONCLUSION: The present study revealed that all students perceived their EE positively. The positive points were that teachers were knowledgeable, that students had good friends, and they were confident about passing their exams. Problem areas observed were authoritarian teachers, overemphasis on factual learning, overly teacher-centered teaching, teachers getting angry, and the need for a support system for stressed students.

Cationic antimicrobial peptide, magainin down-regulates secretion of pro-inflammatory cytokines by early placental cytotrophoblasts.

BACKGROUND: Human placental villous cytotrophoblasts exhibit relative externalization of negatively charged moieties to the outer leaflet of the plasma membrane during the time of syncytialization rendering their reactivity to positively charged cationic antimicrobial peptides (CAMPs) during the window of implantation and early placentation. Vaginal administration of a synthetic CAMP, Ala(8,13,18)-magainin II amide (AMA) inhibited blastocyst implantation and early placentation in monkeys. Furthermore, the administration of AMA resulted in significant inhibition of cell differentiation, enhancement in apoptosis and loss of viability in first trimester placental villous cytotrophoblasts in primary culture. The present study examines the effect of in vitro application of different doses (0, 1, 10, 100, 1000 ng/ml) of AMA on the secreted cytokine profiles of cytotrophoblasts obtained from placental villi samples (n = 13) collected during 8-9 weeks of gestation and grown on three-dimensional collagen matrix in vitro. METHODS: A panel of forty-eight (48) cytokines in conditioned medium was analysed using multiplex immunoassays technique. Further, the steady state transcript levels of four cytokines (CCL4, CCL5, IL1B, IL6), the concentrations of which were affected by AMA in the isolated cytotrophoblasts, as well as, two cytokines (IL1A and TNF) which were not affected by AMA were estimated. Input list of cytokines secreted by cytotrophoblasts and showing differential secretion in response to AMA were used in enrichment analysis for the generation of biological networks. RESULTS: Placental cytotrophoblasts secreted 27 cytokines, 13 of which are affected by AMA in vitro with significantly decreased secretion of CCLs-2, 3, 4, 5, CXCLs-1 and 8, FGF2 and MCSF and that of IL1B, IL6 and MIF, and increased secretion of IL16 and IL-2RA. Of the above cytokines showing differential secretion, only IL-2RA, IL16 and MIF showed significant correspondence in the steady state expression of their respective transcript levels. Post-hoc Enrichment analysis revealed Toll-like receptor (TLR) mediated pathways were the top-scored target pathways that were affected by AMA. CONCLUSIONS: Administration of a CAMP causes shift in the balance of immune-inflammatory responses involving downstream pathways of TLRs in cytotrophoblast function. Further verification of functions of placental trophoblasts on administration of CAMP with pregnancy outcome is necessary.

Evaluation of phytoremediation potential of Tagetes patula L. for the degradation of textile dye Reactive Blue 160 and assessment of the toxicity of degraded metabolites by cytogenotoxicity.

Tagetes patula is an annual flowering plant belonging to family Asteraceae. The present study deals with in vitro decolorization and remediation of a textile dye Reactive Blue 160 by T. patula. There was considerable (∼90%) decolorization of the dye within 4d of incubation, as confirmed by UV-vis, HPLC and FTIR analysis. The enzymes responsible for the remediation were lignin peroxidase, tyrosinase, laccase and NADH-DCIP reductase which were found in root tissues of the plantlets. GC-MS analysis of the products revealed formation of six metabolites such as sodium benzenesulfonate, 6-chloro 1,3,5-triazine-2,4-diamine, disodium benzene-1,4-disulfonate, sodium 3-amino-4-hydroxybenzenesulfonate, 1-phenylmethanediamine and sodium 4-amino-3-carboxybenzenesulfonate after phytoremediation of Reactive Blue 160. Based on the FTIR and GC-MS results, the possible pathway for the biodegradation of Reactive Blue 160 has been traced. The non-toxic nature of the degraded products was confirmed by performing cytogenotoxicity tests on root tip cells of growing Allium cepa.

Acute renal failure associated with malaria in children.

Acute renal failure is one of the serious complications of malaria with untoward consequences including increased risk of mortality. This study was conducted to evaluate the incidence, clinical features, course, outcome, and predictors of mortality of acute renal failure (ARF) in children with malaria in the pediatric general wards and intensive care unit of our medical center from 1 January 2009 to 31 December 2009. Data of all children from 1 month to 12 years of age with confirmed malaria either on peripheral smear and/or OptiMal test were reviewed. Those suffering from ARF were selected for further study. Twelve (eight Plasmodium falciparum; three Plasmodium vivax, and one mixed infection) out of 227 (5%) cases of confirmed malaria had ARF. In addition to ARF, most of the patients had at least one other manifestation of severe malaria. Nine (75%) patients recovered completely, while 3 (25%) died. Presence of associated cerebral malaria, hyperbilirubinemia, and disseminated intravascular coagulopathy (DIC) was a poor prognostic factor and predictor of mortality. In conclusion, ARF can complicate both P. falciparum and P. vivax malaria. Malarial ARF as an isolated complication has a good prognosis. The presence of multiorgan involvement and delayed diagnosis increases morbidity and mortality.

Sesuvium portulacastrum (L.) L.: a potential halophyte for the degradation of toxic textile dye, Green HE4B.

Sesuvium portulacastrum is a common halophyte growing well in adverse surroundings and is exploited mainly for the environmental protection including phytoremediation, desalination and stabilization of contaminated soil. In the present investigation, attempts have been made on the decolorization of a toxic textile dye Green HE4B (GHE4B) using in vitro grown Sesuvium plantlets. The plantlets exhibited significant (70%) decolorization of GHE4B (50 mg l(-1)) that sustain 200 mM sodium chloride (NaCl) within 5 days of incubation. The enzymatic analysis performed on the root and shoot tissues of the in vitro plantlets subjected to GHE4B decolorization in the presence of 200 mM NaCl showed a noteworthy induction of tyrosinase, lignin peroxidase and NADH-DCIP reductase activities, indicating the involvement of these enzymes in the metabolism of the dye GHE4B. The UV-visible spectrophotometer, HPLC and Fourier Transform Infrared Spectroscopy (FTIR) analyses of the samples before and after decolorization of the dye confirmed the efficient phytotransformation of GHE4B in the presence of 200 mM NaCl. Gas Chromatography-Mass Spectroscopy (GC-MS) analysis of the products revealed the formation of three metabolites such as p -amino benzene, p -amino toluene and 1, 2, 7-amino naphthalene after phytotransformation of GHE4B. Based on the FTIR and GC-MS results, the possible pathway for the biodegradation of GHE4B in the presence of 200 mM NaCl has been proposed. The phytotoxicity experiments confirmed the non-toxicity of the degraded products. The present study demonstrates for the first time the potential of Sesuvium for the efficient degradation of textile dyes and its efficacy on saline soils contaminated with toxic compounds.

Textile dye degradation by bacterial consortium and subsequent toxicological analysis of dye and dye metabolites using cytotoxicity, genotoxicity and oxidative stress studies.

The present study aims to evaluate Red HE3B degrading potential of developed microbial consortium SDS using two bacterial cultures viz. Providencia sp. SDS (PS) and Pseudomonas aeuroginosa strain BCH (PA) originally isolated from dye contaminated soil. Consortium was found to be much faster for decolorization and degradation of Red HE3B compared to the individual bacterial strain. The intensive metabolic activity of these strains led to 100% decolorization of Red HE3B (50 mg l(-1)) with in 1h. Significant induction of various dye decolorizing enzymes viz. veratryl alcohol oxidase, laccase, azoreductase and DCIP reductase compared to control, point out towards their involvement in overall decolorization and degradation process. Analytical studies like HPLC, FTIR and GC-MS were used to scrutinize the biodegradation process. Toxicological studies before and after microbial treatment was studied with respect to cytotoxicity, genotoxicity, oxidative stress, antioxidant enzyme status, protein oxidation and lipid peroxidation analysis using root cells of Allium cepa. Toxicity analysis with A. cepa signifies that dye Red HE3B exerts oxidative stress and subsequently toxic effect on the root cells where as biodegradation metabolites of the dye are relatively less toxic in nature. Phytotoxicity studies also indicated that microbial treatment favors detoxification of Red HE3B.

Modulation of stress induced by isometric handgrip test in hypertensive patients following yogic relaxation training.

13 essential hypertensive patients aged 41 to 60 years were given yoga training for 60 min daily, Monday through Saturday, for a total duration of 4 weeks. Blood pressure and heart rate (HR) were measured with non-invasive semi-automatic blood pressure monitor. Measurements were recorded before the training and at weekly intervals during the 4 week training period. Results of our study show a significant (P<0.001) reduction in resting HR and rate-pressure-product (RPP) after 2 weeks of yoga training. Systolic pressure (SP), diastolic pressure (DP) (P<0.001) and mean pressure (MP) (P<0.05) showed a significant reduction at 3 weeks of training period. After 4 weeks of training, there was further fall in SP, DP, pulse pressure (PP) (P<0.05), MP (P<0.001), HR and RPP. Isometric handgrip test before yoga training produced a significant rise in SP and MP and insignificant rise in DP, HR and RPP. After yoga training, there was a significant rise in all these parameters. Our results show that yoga training optimises the sympathetic response to stressful stimuli like isometric handgrip test and restores the autonomic regulatory reflex mechanisms in hypertensive patients.