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Nowadays, nanotechnology is extensively employed in the medical profession. In this study, we used the aqueous extract of the bark of Mitragyna parvifolia to synthesize silver nanoparticles (AgNPs) by microwave-assisted green synthesis. The synthesis of AgNPs was confirmed by visual color change to brown color and characteristic surface plasmon resonance peak at 432 nm. The hydrodynamic diameter of the AgNPs was 171.81 nm having a zeta potential of −24.14 mV; Fourier Transmission Infrared Spectroscopy confirmed the presence of different functional groups on the NP surface; Scanning Electron Microscope and High-Resolution Transmission Electron Microscopy indicated predominantly circular shape of nanoparticle; Selected Area Electron Diffraction and X-ray Diffraction analyses determined the crystalline structure of AgNPs. Energy-Dispersive X-ray indicated the elemental composition and formation of AgNPs. The AgNPs were screened at different concentrations for antioxidant activity, antimicrobial, and anticancer potential in breast cancer cells (MCF-7 and MDA-MB-231). The AgNPs exhibited remarkable antioxidant, antimicrobial, and anticancer activities. The sedative and antinociceptive activities were also tested on Swiss albino mice, which showed mild sedative and very potent antinociceptive activity. However, detailed mechanistic studies are warranted in the future for clinical application of the AgNPs as a biologically active agent as well as a carrier for drug delivery.

Abstract Background Diabetic foot ulcer (DFU) is a major complication of diabetes often impacted by polymicrobial infection in the wound site. Diabetic patients are immunocompromised in nature and hence vulnerable to infection once the skin barrier is breached. Microbiological culture-based methods show that Staphylococcus aureus (SA) is the most frequently isolated bacteria from the DFU wounds. SA and its most clinically important antibiotic resistant variant methicillin-resistant S. aureus (MRSA) are commonly found in the nasal vestibule and colonization of SA as well as MRSA in any wound site can aggravate the condition. We hypothesize that the presence of nasal MRSA carriage can serve as a potential risk factor contributing to the emergence of antibiotic resistance in diabetic foot ulcer wounds. Methods In the present study, we have compared the carriage of SA and MRSA in nasal cavity and foot skin among DFU patients (D+F+, n = 50), diabetic patients without any ulcer (D+F-, n = 50), and healthy controls (D-F-, n = 40) by using bacterial culture and PCR based methods. The D+F+, D+F- and D-F-individuals were further categorized based on the presence or absence of MRSA and clinical parameters were compared between MRSA+ ve and MRSA-ve individuals in each of the three groups mentioned above. Results Our results show that, (a) nasal MRSA carriage is significantly higher (p

Out of several heterocyclic templates, the use of a Benzimidazole (BZ) scaffold is immensely observed. This fused heterocycle comprises two ring nitrogen atoms placed at 1st and 3rd position, in which the 1st nitrogen is connected to hydrogen that gets released to exhibit the acidic property. The use of BZ for the purpose of making clinically useful compounds was started in the year of 1944. BZ derivatives have been consistently used as effective chemotherapeutic agents to treat a diverse range of disorders. Apart from their clinical usefulness, BZ-based compounds also confer high safety, bio-availability, and stability. Out of several clinical conditions, cancer, and helminthiasis are a few where this template has been maximally utilized. The present review emphasizes chronologically the developments of BZ-based compounds in the entire scope of medicinal chemistry as antibacterial, anticancer, antifungal, anti-inflammatory, anti-HIV (human immunodeficiency virus), anticonvulsant, antioxidant, antidiabetic, antitubercular, antileishmanial, antimalarial, anti-histaminic. This review also covers patents on BZ of clinical importance till 2020. The primary objective of this review is to develop a comprehensive SAR (structure–activity relationship), which in turn assists the medicinal chemist to come up with novel ideas, while being implemented could produce novel compounds with enormous potential.

ABSTRACT The pandemic caused by the SARS-CoV-2 virus is the reason for many deaths globally. It is hypothesized that the upper respiratory tract (URT) microbiome shares similarities with lung microbiota and can modulate host immune responses to the virus. During the pandemic, several SARS-CoV-2 variants have emerged with different clinical outcomes and immune dysfunction, yet their association with changes in the URT microbiome has not been identified, which may provide an assessment of lung health in the presence of those variants with differential disease outcomes. In this study, we sequenced V3–V4 region of the 16S rRNA gene from the URT microbiome of healthy controls (HC), Delta- and Omicron-infected patients from Eastern India, which showed higher inter-individual diversity (β) and lower intra-individual diversity (α) in COVID-19 patients compared to healthy controls. Healthy control microbiome showed enrichment of commensals like Streptococcus symci, Prevotella melaninogenica, Neisseria perflava, Veillonella tobetsuensis, Veillonella nakazawae, Haemophilus parainfluenzae, Fusobacterium pseudoperiodonticum, and Bifidobacterium longum compared to COVID-19 samples. Ct value of patients significantly positively correlated with Streptococcus symci and Streptococcus toyakuensis indicating a possible inverse relation with viral load. We also observed few bacterial taxa like Staphylococcus caprae, Pseudomonas aeruginosa, Vibrio tritonious, and Rothia mucilaginosa are discriminating Omicron from Delta which is, in turn, enriched mostly with Enterobacter mori, Acinetobacter baumannii, and Klebsiella pneumoniae. Further investigation showed nine control-associated bacteria had higher to lower trends among three groups viz., Control > Omicron > Delta. These bacteria also contributed to the successful prediction of disease groups with high accuracy (90% ± 0.5%) by random forest analysis. IMPORTANCE The role of the upper respiratory tract (URT) microbiome in predicting lung health has been documented in several studies. The dysbiosis in COVID patients has been associated with disease outcomes by modulating the host immune system. However, although it has been known that different SARS-CoV-2 variants manifest distinct transmissibility and mortality rates in human populations, their effect on the composition and diversity of the URT microbiome has not been studied to date. Unlike the older variant (Delta), the newer variant (Omicron) have become more transmissible with lesser mortality and the symptoms have also changed significantly. Hence, in the present study, we have investigated the change in the URT microbiome associated with Delta and Omicron variants and identified variant-specific signatures that will be useful in the assessment of lung health and can be utilized for nasal probiotic therapy in the future.

Purpose: Keratoconjunctivitis sicca (KCS) or dry eye disease (DED) is a multifactorial disease that results in discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. A pilot study was undertaken to determine if there were any major substantial differences in the ocular microbiome in DED patients versus healthy controls. Methods: The bacterial communities residing in the conjunctiva of patients with DED (n = 4) and healthy controls (n = 4) were assessed by 16S ribosomal RNA (rRNA) gene sequencing of the V4–V5 region. Results: The phyla Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes were most dominant and accounted for 97% and 94.5% of all bacterial sequences in patients and controls, respectively. At the genus level, 27 bacterial genera were found with more than two-fold difference between patients and controls. Four of these – Acinetobacter, Corynebacterium, Lactobacillus, and Pseudomonas spp. – dominated the ocular microbiome of all subjects, but were proportionately lower in DED (16.5%) compared to controls (37.7%). Several bacterial genera were found to be unique in DED (34) and controls (24). Conclusion: This pilot study is an attempt to profile the ocular microbiome in patients with DED that demonstrated a higher concentration of microbial DNA compared to controls, with Firmicutes phyla dominating the bacterial population in patients with DED.

Abstract Background The Lambert-Eaton myasthenic syndrome (LEMS) is a rare disorder characterized by proximal muscle weakness and autonomic dysfunction due to involvement of the neuromuscular junction A case of delayed unilateral recovery from spinal anesthesia in a patient with LEMS undergoing open cholecystectomy is described. Case presentation A 42-year-old lady, on treatment for LEMS with pyridostigmine, prednisolone, and azathioprine presented with cholelithiasis and was scheduled for open cholecystectomy. Neuraxial anesthesia combined with a light plane of general anesthesia provided adequate muscle relaxation without the use of neuromuscular blocking drugs. In spite of perioperative continuation of anticholinesterases, the patient required 12 h post-surgery for complete bilateral motor recovery from spinal anesthesia. Conclusions A combination of spinal anesthesia with a light plane of general anesthesia appears to be a safe anesthetic technique for managing patients with Lambert-Eaton myasthenic syndrome undergoing open cholecystectomy. However, neurologically asymptomatic patients with good treatment compliance may also show an unusual delay in recovery from neuraxial anesthesia.

ABSTRACT Characterization of the oral microbiota profile through various studies has shown an association between the microbiome and oral cancer; however, stage-specific determinants of dynamic changes in microbial communities of oral cancer remain elusive. Additionally, the influence of the intratumoral microbiota on the intratumoral immune system remains largely unexplored. Therefore, this study aims to stratify microbial abundance in the early-onset and subsequent stages of oral cancer and analyze their influence on clinical-pathological and immunological features. The microbiome composition of tissue biopsy samples was identified using 16S rRNA amplicon sequencing, while intratumoral and systemic immune profiling was done with flow cytometry and immunohistochemistry-based analysis. The bacterial composition differed significantly among precancer, early cancer, and late cancer stages with the enrichment of genera Capnocytophaga, Fusobacterium, and Treponema in the cancer group, while Streptococcus and Rothia were enriched in the precancer group. Late cancer stages were significantly associated with Capnocytophaga with high predicting accuracy, while Fusobacterium was associated with early stages of cancer. A dense intermicrobial and microbiome-immune network was observed in the precancer group. At the cellular level, intratumoral immune cell infiltration of B cells and T cells (CD4+ and CD8+) was observed with enrichment of the effector memory phenotype. Naive and effector subsets of tumor-infiltrating lymphocytes (TILs) and related gene expression were found to be distinctly associated with bacterial communities; most importantly, highly abundant bacterial genera of the tumor microenvironment were either negatively correlated or not associated with the effector lymphocytes, which led to the conclusion that the tumor microenvironment favors an immunosuppressive and nonimmunogenic microbiota. IMPORTANCE The gut microbiome has been explored extensively for its importance in the modulation of systemic inflammation and immune response; in contrast, the intratumoral microbiome is less studied for its influence on immunity in cancer. Given the established correlation between intratumoral lymphocyte infiltration and patient survival in cases of solid tumors, it was pertinent to explore the extrinsic factor influencing immune cell infiltration in the tumor. Modulation of intratumoral microbiota could have a beneficial effect on the antitumor immune response. This study stratifies the microbial profile of oral squamous cell carcinoma starting from precancer to late-stage cancer and provides evidence for their immunomodulatory role in the tumor microenvironment. Our results suggest combining microbiome study with immunological signatures of tumors for their prognostic and diagnostic application.

In spite of the advent of many high throughput technologies, tumor tissue biomarkers are still the gold standard for diagnosis and prognosis of different malignancies including epithelial ovarian cancer (EOC). EOC is a heterogeneous disease comprised of five major subtypes which show distinct clinicopathological features and therapy response. Acquirement of chemoresistance toward therapy is a major challenge for successful treatment outcome in EOC patients. Several markers have been tested by immunohistochemical method to evaluate their prognostic merit to predict clinical outcome. However, a vast majority of such markers have been assessed for high-grade serous and clear cell ovarian cancer, among all subtypes of EOC. The current review elaborates upon those biomarkers that can potentially predict chemoresistance with subtype specificity.

BackgroundThe incidence of preterm birth (PTB) in India is around 13%. Specific bacterial communities or individual taxon living in the vaginal milieu of pregnant women is a potential risk factor for PTB and may play an important role in its pathophysiology. Besides, bacterial taxa associated with PTB vary across populations.ObjectiveConduct a comparative analysis of vaginal microbiome composition and microbial genomic repertoires of women who enrolled in the Interdisciplinary Group for Advanced Research on Birth Outcomes – A DBT India Initiative (GARBH-Ini) pregnancy cohort to identify bacterial taxa associated with term birth (TB) and PTB in Indian women.MethodsVaginal swabs were collected during all three trimesters from 38 pregnant Indian women who delivered spontaneous term (n=20) and preterm (n=18) neonates. Paired-end sequencing of V3-V4 region of 16S rRNA gene was performed using the metagenomic DNA isolated from vaginal swabs (n=115). Whole genome sequencing of bacterial species associated with birth outcomes was carried out by shotgun method. Lactobacillus species were grown anaerobically in the De Man, Rogosa and Sharpe (MRS) agar culture medium for isolation of genomic DNA and whole genome sequencing.ResultsVaginal microbiome of both term and preterm samples reveals similar alpha diversity indices. However, significantly higher abundance of Lactobacillus iners (p-value All_Trimesters

Background: Atopic Dermatitis (AD) has been associated with the loss of function (LoF) mutations in Filaggrin (FLG) gene and increase in relative abundance of specific microbes in the lesional skin, predominantly in Caucasians. Our study aims to determine, in Indian AD patients, (a) the prevalence of FLG LoF and missense mutations, and (b) the nature and extent of dysbiosis and altered microbial pathways with and without mutations in FLG. AD patients (n = 34) and healthy controls (n = 54) were recruited from India in this study and shotgun sequencing was carried out in a subset of samples with adequate microbiome DNA concentration. Host DNA from the same subset of samples was subjected to FLG coding region sequencing and host-microbiome association was estimated.Results: The prevalence of FLG LoFs that are associated with AD globally were significantly lesser in our cases and controls (8.6%, 0%) than those reported in Europeans (27%, 2.6%). Staphylococcus aureus was present only on AD skin [abundance in Pediatric AD: 32.86%; Adult AD: 22.17%], but not on healthy skin on which Staphylococcus hominis (Adult controls: 16.43%, Adult AD: 0.20%; p = 0.002), Cutibacterium acnes (Adult controls:10.84%, Adult AD: 0.90%; p = 0.02), and Malassezia globosa (Adult controls: 8.89%, Adult AD: 0.005%; p = 0.001) were significantly more abundant. Microbial pathways mostly associated with skin barrier permeability, ammonia production and inflammation (Arginine and Proline metabolism, Histidine Metabolism and Staphylococcus aureus infection) were significantly enriched on AD skin metagenome. These pathways are also reported to impair antimicrobial peptide activity. Among AD patients with missense single nucleotide polymorphisms harboring “potentially damaging” alleles in FLG gene, damaging allele dosage was significantly (p < 0.02) positively correlated with relative abundance of phylum_Proteobacteria up to order_Pseudomonadales and negatively correlated with phylum_Firmicutes up to species_Staphylococcus aureus.Conclusion: Our study has provided evidence that host DNA profile is significantly associated with microbiome composition in the development of AD. Species and strain level analysis showed that the microbial pathways enriched in AD cases were mostly found in MRSA strains. These evidences can be harnessed to control AD by modulating the microbiome using a personalized strategy. Our findings on the association of FLG genotypes with the microbiome dysbiosis may pave the way for a personalized strategy to provide a more effective control of AD.

The treatment of colonialism in video games, barring a few notable exceptions, is marked by a Western and, specifically, late 19th-century imperialist bias. Simultaneously, in the past two decades of multifaceted research and the development of robust theoretical frameworks in the still fledgling discipline of game studies, postcolonial discourses, whether they comprise critiques of imperialism or neocolonialism, have not been prominently highlighted until very recently. A coherent effort to bring together the current research on postcolonialism in video games was also urgently required. Further, the past years has seen a rather persistent, albeit unexpected, emergence of a pro-colonial or pro-imperialist discourse in mainstream academia that even justifies the continuance of empire as an ameliorating influence on the people of the so-called developing countries, most of which had formerly been colonized by European powers.Thus, it is the aim of this issue to address this epistemic omission and counter such bias where it exists by also bridging video games research with larger discussions of postcolonialism in other humanities contexts and disciplines. The various articles in this special issue offer a range of perspectives from epistemological power to theory and praxis in critical academia, to contexts of production and practices of play, to close readings of postcolonial traces in video games. These varying approaches to the analysis of video games and their societal and historical contexts open up the debates further to a diverse set of topics ranging from board games to phone games or from mainstream high-budget console games to indie titles that question colonialism. As video games address issues relating to orientalism, subalternity, and hybridity as well as the current ambiguities in conceiving nationhood and the postcolony, the articles in this issue will also likely adumbrate further serious commentary that will develop both game studies research and current conceptions of the postcolonial.