Showing papers by "Anoop Kumar published in 2022"
TL;DR: In this paper , the suitability of Gold and Bitcoin as safe-haven instruments in the backdrop of the Covid-19 related equity market meltdown was tested by implementing the newly proposed Wavelet Quantile Correlation.
31 citations
TL;DR: The findings suggest that LA treatment has beneficial systemic effects that can potentially be developed as a safe OA disease-modifying drug (OADMD), as reflected by rapid joint pain reduction, cartilage protection, and reversal of dysbiosis.
Abstract: To test probiotic therapy for osteoarthritis (OA), we administered Lactobacillus acidophilus (LA) by oral gavage (2×/week) after induction of OA by partial medial meniscectomy (PMM). Pain was assessed by von Frey filament and hot plate testing. Joint pathology and pain markers were comprehensively analyzed in knee joints, spinal cords, dorsal root ganglia and distal colon by Safranin O/fast green staining, immunofluorescence microscopy and RT-qPCR. LA acutely reduced inflammatory knee joint pain and prevented further OA progression. The therapeutic efficacy of LA was supported by a significant reduction of cartilage-degrading enzymes, pain markers and inflammatory factors in the tissues we examined. This finding suggests a likely clinical effect of LA on OA. The effect of LA treatment on the fecal microbiome was assessed by 16S rRNA gene amplicon sequencing analysis. LA significantly altered the fecal microbiota compared to vehicle-treated mice (PERMANOVA p < 0.009). Our pre-clinical OA animal model revealed significant OA disease modifying effects of LA as reflected by rapid joint pain reduction, cartilage protection, and reversal of dysbiosis. Our findings suggest that LA treatment has beneficial systemic effects that can potentially be developed as a safe OA disease-modifying drug (OADMD).
6 citations
TL;DR: The overall results indicate that the PLNs-kNGR-NPs-based hybrid lipid–polymer nanoparticles present the highest therapeutic efficacy against solid tumor overexpressing the CD13 receptors.
Abstract: The present study aims to design, develop and characterize kNGR (Asn-Gly-Arg) peptide-conjugated lipid–polymer-based nanoparticles for the target-specific delivery of anticancer bioactive(s), i.e., Paclitaxel (PTX). The kNGR-PEG-DSPE conjugate was synthesized and characterized by using spectral analysis. The dual-targeted PLGA–lecithin–PEG core-shell nanoparticles (PLNs-kNGR-NPs) were synthesized using a modified nanoprecipitation process, and their physiological properties were determined. The results support that, compared to other NPs, PLNs-kNGR-NPs are highly cytotoxic, owing to higher apoptosis and intracellular uptake. The significance of rational nanoparticle design for synergistic treatment is shown by the higher tumor volume inhibition percentage rate (59.7%), compared to other designed formulations in Balb/c mice in the HT-1080 tumor-induced model. The overall results indicate that the PLNs-kNGR-NPs-based hybrid lipid–polymer nanoparticles present the highest therapeutic efficacy against solid tumor overexpressing the CD13 receptors.
5 citations
TL;DR: A novel mechanism for post transcriptional regulation of NHE-3 by miR-326 and -330-5p by translational repression is demonstrated and it is speculated that miR+ /H+ exchanger-3 dependent pathways may be involved in modulating N HE-3 expression under physiological and pathophysiological conditions.
Abstract: Na+ /H+ exchanger-3 (NHE-3) is the major apical membrane transporter involved in vectorial Na+ absorption in the intestine. Dysregulation of NHE-3 expression and/or function has been implicated in pathophysiology of diarrhea associated with gut inflammation and infections.Therefore, it is critical to understand the mechanisms involved in the regulation of NHE-3 expression. MicroRNAs (miRNAs) are highly conserved small RNAs that can regulate gene expression at the post transcriptional level. To date, however, very little is known about the regulation of NHE-3 expression by microRNAs. Therefore, current studies were undertaken to examine the potential miRNA candidates that can regulate the expression of NHE-3 in intestinal epithelial cells. In silico analysis, using different algorithms, predicted several miRNAs that target NHE-3. MicroRNAs with highest context and target score, miR-326, miR-744-5p and miR-330-5p, were selected for the current study. Human NHE-3 gene 3'UTR (160 bp) was cloned into pmirGLO vector upstream of luciferase reporter and transiently transfected with mimics of miR-326, miR-744-5p and miR-330-5p into Caco-2, HT-29 and SKCO-15 cells. Co-transfection of NHE-3 3' UTR with miR-326 and -miR-330-5p mimics resulted in a significant decrease in relative luciferase activity. Transfection of miR- 326 and 330-5p mimics into SK-CO15 cells significantly decreased the NHE-3 protein expression, with no change in NHE-3 mRNA levels. Our findings demonstrate a novel mechanism for post transcriptional regulation of NHE-3 by miR-326 and -330-5p by translational repression. We speculate that miR-326 and -330-5p dependent pathways may be involved in modulating NHE-3 expression under physiological and pathophysiological conditions.
3 citations
TL;DR: In this article , the authors investigated the mechanisms by which loss of DRA relays signals to immune cells to increase susceptibility to inflammation in colorectal ulcerative colitis.
Abstract: Background & AimsDown-regulation of chloride transporter SLC26A3 or down-regulated in adenoma (DRA) in colonocytes has recently been linked to the pathogenesis of ulcerative colitis (UC). Because exaggerated immune responses are one of the hallmarks of UC, these current studies were undertaken to define the mechanisms by which loss of DRA relays signals to immune cells to increase susceptibility to inflammation.MethodsNanoString Immunology Panel, fluorescence assisted cell sorting, immunoblotting, immunofluorescence, and quantitative real-time polymerase chain reaction assays were used in wild-type and DRA knockout (KO) mice. Interleukin (IL)-33 blocking was used to determine specific changes in immune cells and co-housing/broad spectrum antibiotics administration, and ex vivo studies in colonoids were conducted to rule out the involvement of microbiota. Colonoid-derived monolayers from healthy and UC patient biopsies were analyzed for translatability.ResultsThere was a marked induction of Th2 (>2-fold), CD4+ Th2 cells (∼8-fold), RORγt+ Th17, and FOXP3+ regulatory T cells (Tregs). DRA KO colons also exhibited a robust induction of IL-33 (>8-fold). In vivo studies using blocking of IL-33 established that T2 immune dysregulation (alterations in ILC2, Th2, and GATA3+ iTregs) in response to loss of DRA was due to altered epithelial-immune cell crosstalk via IL-33.ConclusionsLoss of DRA in colonocytes triggers the release of IL-33 to drive a type 2 immune response. These observations emphasize the critical importance of DRA in mucosal immune homeostasis and its implications in the pathogenesis of UC. Down-regulation of chloride transporter SLC26A3 or down-regulated in adenoma (DRA) in colonocytes has recently been linked to the pathogenesis of ulcerative colitis (UC). Because exaggerated immune responses are one of the hallmarks of UC, these current studies were undertaken to define the mechanisms by which loss of DRA relays signals to immune cells to increase susceptibility to inflammation. NanoString Immunology Panel, fluorescence assisted cell sorting, immunoblotting, immunofluorescence, and quantitative real-time polymerase chain reaction assays were used in wild-type and DRA knockout (KO) mice. Interleukin (IL)-33 blocking was used to determine specific changes in immune cells and co-housing/broad spectrum antibiotics administration, and ex vivo studies in colonoids were conducted to rule out the involvement of microbiota. Colonoid-derived monolayers from healthy and UC patient biopsies were analyzed for translatability. There was a marked induction of Th2 (>2-fold), CD4+ Th2 cells (∼8-fold), RORγt+ Th17, and FOXP3+ regulatory T cells (Tregs). DRA KO colons also exhibited a robust induction of IL-33 (>8-fold). In vivo studies using blocking of IL-33 established that T2 immune dysregulation (alterations in ILC2, Th2, and GATA3+ iTregs) in response to loss of DRA was due to altered epithelial-immune cell crosstalk via IL-33. Loss of DRA in colonocytes triggers the release of IL-33 to drive a type 2 immune response. These observations emphasize the critical importance of DRA in mucosal immune homeostasis and its implications in the pathogenesis of UC.
2 citations
TL;DR: In this article , a qualitative content analysis of declarations published by seven Indian fact-checkers on their websites demonstrates that fact-checking is conducted in a systemic and transparent manner and that compliance to transparency is an important tenet of journalistic professionalism.
Abstract: Among other preventive measures, fact-checking is considered as one of the effective ways to combat fake news. Fact-checkers promote rationality and assist citizens in making informed decisions. However, fact-checkers’ motives, methods and abilities are doubted and subjected to distrust. Lack of perceived trust is a major concern in the profession of fact-checking journalism. To build public trust, fact-checking organisations have been advised to be transparent about news production processes. Besides the trust mechanism, compliance to transparency is an important tenet of journalistic professionalism. This study seeks to analyse Indian fact-checkers’ explanations of their methodology for fact-checking claims and commitments to ensuring methodological transparency. Qualitative content analysis of declarations published by seven Indian fact-checkers on their websites demonstrates that fact-checking is conducted in a systemic and transparent manner. Transparency norm seems to have emerged as a governing principle in the context of fact-checking journalism. The findings of this study have been interpreted in the view of literature on journalistic transparency.
1 citations
TL;DR: In this paper , the authors evaluate government policies for MSME and how these companies work under these policies and support and measure performance and business engagement using secondary data with an analytical approach.
Abstract: For the development and growth of the country, the government must actively promote the development of the organisation. Small and medium enterprises (MSMEs) among for-profit companies deserve special attention. SMEs are small investment companies with enormous stakes. The sector contributes over 28% of the GDP and almost 45% to the manufacturing output. The most common organisational model in many countries, the Ministry of Small and Medium Enterprises (MSMEs), is crucial to developing a market economy. It employs almost 111 million people. The sector acts as the instrument of inclusive growth, empowering the most vulnerable and marginalised groups. There are around 6.3 crore MSME units in the country, with over 99% categorised as small units (as per the original definition). The choice depends on many factors, including public attitudes toward entrepreneurs—human structure, Size and role of Current government, level of entrepreneurial activity and prevalence of existing MSMEs. The present study evaluates government policies for MSME and how these companies work under these policies and support. This paper aims to review government policies and SME development in India 2020-21 and measure performance and business engagement. The article used the approach of secondary data with an analytical approach. To fulfil the study’s objectives.
TL;DR: The current studies were undertaken to examine the role of desmosomes and Rho‐ROCK‐MLC phosphorylation pathway in colonic barrier integrity in DRA KO mice.
Abstract: DRA or SLC26A3 is the key transporter for chloride absorption in the mammalian intestine. Our recent studies demonstrated that DRA deficiency increased paracellular permeability and altered tight and adherens junction protein expression in mouse colon. However, the mechanisms underlying increased paracellular permeability and the role of intercellular junctional proteins (desmosomes) that play a critical role in the maintenance of intestinal barrier integrity in DRA KO mice are not well understood. Aim The current studies were undertaken to examine the role of desmosomes and Rho‐ROCK‐MLC phosphorylation pathway in colonic barrier integrity in DRA KO mice.
TL;DR: In this article , a retrospective analysis of patients who underwent percutaneous dilatational tracheostomy (PDT) admitted to ICU between 2006 and 2021 was performed.
Abstract: Introduction: Tracheostomy is one of the most frequent surgical procedures carried out in critically ill patients. The most popular technique today is the percutaneous dilatational tracheostomy (PDT) which uses serial dilators over a guide wire and is usually done at the bedside in the intensive care unit (ICU) under bronchoscopic guidance. Antiplatelet agents have become a mainstay therapy for vascular diseases; yet they increase the risk of bleeding. The aim of this study is to determine the bleeding risk for patients on antiplatelet therapy who underwent PDT. Methods: A retrospective analysis of patients who underwent PDT admitted to ICU between 2006 and 2021. All data were extracted from electronic health record (EPIC) and operative reports. Minor bleeding is defined as bleeding requiring application of temporary pressure or change of dressing. Major bleeding is defined as bleeding requiring packing with surgicel or transfusion of red blood cells, fresh frozen plasma or platelets. Antiplatelet therapy (APT) is defined as receiving therapy up to and within 24 hours of PDT. Single antiplatelet therapy (SAT) is ASA alone and dual antiplatelet therapy (DAT) is ASA/clopidogrel combination. Results: A total of 677 PDTs were identified and analyzed (567 patients that did not receive antiplatelet therapy [NAT group] and 100 APT group [93 SAT and 17 DAT]). Compared to the NAT group, the APT group were older (71 +/- 12 vs 58 +/- 20, p = 0.0001), had similar gender (male: 60 % vs 60 %, p = 1.0), and similar BMI (29 +/- 9 vs 28 +/- 7, p = 0.2). For minor bleeding (5.1 % in NAT group), the SAT group and DAT group had more bleeding (17 % for SAT, p = 0.0001, and 17.6 % for DAT, p = 0.02). Major bleeding did not significantly differ between SAT and NAT groups (1.1 % vs 0.4 %, p = 0.2), but was significantly higher for DAT group compared to NAT group (5.9 % vs 0.4 %, p = 0.003). Conclusions: In a large single center, there was no significant major bleeding when PDT was performed while patients are on ASA, but there was significantly more major bleeding when patients were on both ASA and clopidogrel. This data should be confirmed in large multicenter prospective studies.
TL;DR: Loss of DRA from colonocytes triggers the release of the IL‐33 to drive a type 2 immune response in UC, emphasizing the critical importance of loss of D RA and its implications in the pathogenesis of UC.
Abstract: Down Regulated in Adenoma (DRA), the major chloride transporter in the mammalian intestine has recently emerged as a critical gene contributing to the pathogenesis of Ulcerative Colitis (UC). We have previously shown that DRA knockout (KO) mice display several features of UC including compromised barrier function and dysbiosis. Further, DRA KO mice show increased susceptibility to intestinal inflammation. To elucidate the mechanisms by which loss of DRA could impact gut inflammation, gene expression between DRA KO and wild type littermate controls (WT) by RNAseq was compared. The data showed that out of 1100 genes differentially expressed in DRA KO colon, majority were related to immune responses. Upon conducting more specific immune based analysis using nanoString nCounter® Immunology Panel, we observed a significant upregulation of genes promoting effector T cell expansion, specifically Th2. Interleukin‐33 (IL‐33), an alarmin cytokine is known to be significantly upregulated in colons of UC patients and is a key driver of type 2 immune cell expansion. Since alterations in epithelial‐immune cell crosstalk can trigger inflammatory responses, we hypothesized that DRA KO mice may have aberrant epithelial‐immune cell crosstalk which could trigger changes in Lamina Propria Lymphocytes (LPLs). Following isolation of colonic LPLs and staining for various innate and adaptive immune cells, we detected a significant increase (> 2‐fold) in type 2 innate lymphoid cells (ILC2) and in Th2 cells(~8‐fold) in DRA KO mice which were both GATA3+. These observations were specific to the colon and not seen in the ileal LP or mesenteric lymph nodes. We also observed a significant induction of type 2 effector protein amphiregulin, demonstrating an increased type‐2 immune tone in DRA KO colons. Since IL‐33 is important for immune cell activation following tissue injury at mucosal surfaces we analyzed IL‐33 protein levels in the colon. IL‐33 was markedly elevated in DRA KO colons and appeared to be independent of microbiome changes as this increase in IL‐33 still persisted even after cohousing with WT mice for over 4 weeks (allowing exchange of the microbiome). Confocal imaging of colonic tissues and colonoids further confirmed the increase in epithelial IL‐33 and its dissemination from the nucleus to the cytoplasm in DRA KO colonocytes. Since IL‐33 is known to specifically expand a subset of T regs which are also GATA3+; we gated LPLs double positive for FOXP3 and GATA3 using FACS. Interestingly, total T regs and GATA3+ T regs were both markedly elevated in DRA KO colonic LP compared to WT, confirming the functional relevance of increased IL‐33. These results were further validated in human colonoid derived monolayers where DRA was significantly reduced parallel to upregulation of IL‐33 protein in UC, mirroring the results from DRA KO mice. In conclusion, loss of DRA from colonocytes triggers the release of the IL‐33 to drive a type 2 immune response. These observations emphasize the critical importance of loss of DRA and its implications in the pathogenesis of UC.
TL;DR: In this article , the authors used mutual azo prodrugs (S1-S5) to treat inflammatory bowel disease (IBD) and evaluated the colon-targeted release (in-vitro and in-vivo release studies).
Abstract: Several adverse effects are related to medications that treat moderate to severe inflammatory bowel diseases (IBDs). Targeted drug administration is necessary to treat inflammatory bowel disease to maximize efficacy and minimize toxicity. This study investigated the prodrug approach for antibacterials that target the colon. We chose sulfonamide (Sulfamethoxazole) as an antibiotic to target the colon. The prodrug approach is one of the most effective treatments for inflammatory bowel disease (IBD), and this mutual azo prodrug might serve the same function. This investigation aims to synthesize mutual azo prodrugs (S1-S5) and evaluate the colon-targeted release (in-vitro and in-vivo release studies). The objective of synthesizing mutual azo prodrugs (S1- S5) is that due to the high molecular weight of synthesized prodrugs (>500), they will enter the colon intact and not be absorbed in the upper GIT (Lipinski rule of 5). A coupling reaction between the sulfamethoxazole diazonium salt and salicylic acid derivatives allowed for synthesizing of mutual azo prodrugs (S1-S5). By monitoring the chemical reactions, the purity of the synthesized prodrugs was assessed, and by using FTIR, NMR (1H and 13C), Mass Spectrometry (MS), and Elemental Analysis, the structures of newly synthesized mutual azo prodrugs (S1-S5) were analyzed. Studies on the in-vitro stability of synthesized prodrugs showed less release after 6 hours in HCl buffer (pH 1.2), and only 10% release after 6 hours in phosphate buffer (pH 7.4) was observed. The sensitivity of the synthesized azo prodrug to the bacterial enzyme azoreductase was shown by incubating the azo prodrugs with the cecal contents of a rat; the release results showed that the release of free drugs from the azo prodrugs was more than 80%. Using trinitrobenzene sulfonic acid (TNBS)-induced colitis rats model, the in-vivo study was evaluated, and results revealed that mutually synthesized azo prodrugs are effective as 5-aminosalicylic acid in ulcerative colitis. Based on the release studies results, it is concluded that the azo prodrugs are a potential therapeutic target for ulcerative colitis.
TL;DR: The effect of removing of IEC AhR in an inducible manner utilizing DSS induced chronic colitis is investigated and the underlying mechanisms are elucidated.
Abstract: Inflammatory Bowel Diseases (IBD), including Crohn’s Disease (CD) and ulcerative colitis (UC), are associated with chronic inflammation of the gastrointestinal tract. While it is a multifactorial disease, recently the aryl hydrocarbon receptor (AhR) has been identified as a susceptibility gene for IBD. AhR is a ubiquitously expressed transcription factor and its activation results in xenobiotic detoxification by CYP1A1 and CYP1B1, as well as induction of anti‐inflammatory pathways such as IL‐10 and IL‐22. In the gut, AhR is vital in maintaining immune cell populations, proliferation, and motility. Previous studies utilizing constitutive knock out of AhR in IECs showed exacerbated inflammation in acute DSS model. How intestinal epithelial cell (IEC) AhR deficiency impacts chronic colitis resembling human IBD is not yet known. Here, we investigated the effect of removing of IEC AhR in an inducible manner utilizing DSS induced chronic colitis (resembling Th1/Th17 and Th2 infiltration as seen in CD patients) and elucidated underlying mechanisms.
TL;DR: In this article , a series of EDTA-antimicrobial drug conjugates (E1-E5) were synthesized by stirring tetra sodium EDTA with antimicrobial drugs.
Abstract: Background: The colon targeted drug delivery system is mainly useful for the topical treatment of colon diseases such as ulcerative colitis, Crohn’s disease OR colorectal cancers where we attain high local concentration and minimum side effects. In the present study we have synthesized some colon targeted Ethylene diamine tetra acetic acid (EDTA)-antimicrobial drug conjugates. Objectives: The goal of synthesizing EDTA-antimicrobial drug conjugates are that they reach intact in the colon and not be absorbed in the upper GIT, this is because of high molecular weight (>500) of the conjugates (Lipinski’s rule of 5). Materials and Methods: A series of EDTA-antimicrobial drug conjugates (E1-E5) were synthesized by stirring tetra sodium EDTA with antimicrobial drugs viz. Metronidazole (MTZ), Ornidazole (OZ), Ciprofloxacin (CF), Norfloxacin (NF) and Sulfamethoxazole (SM) in presence of EDAC ((1-ethyl-3(3-dimethylaminopropyl) carbodiimide). All the synthesized conjugates were characterized by FTIR, NMR (1H and 13C), Mass spectrometry and elemental analysis to identify structural components. The synthesized conjugates were screened for antimicrobial (antibacterial) and colon release studies. Results and Discussion: On the basis of chemical and spectral analysis EDTA-antimicrobial drug conjugates were synthesized and synthesized conjugates showed good antimicrobial (antibacterial) activity against tested stains. In-vitro release studies of the synthesized conjugates of the series have shown good release results which indicates that synthesized conjugates release the parent drug (antimicrobial drugs) to the colon. Conclusion: Synthesized conjugates improve drug delivery to the intestinal region. Release studies result suggest that the drugs begin to release from the conjugates in the distal intestinal region and appreciable release in the colon has been observed.
TL;DR: In this article , a self nano emulsifying formulation (SNF) was proposed to improve Cefpodoxime proxetil (CPD) solubilization by developing a CO-based fully dilutable self-nodes emulsion formulation and assessment of its antibacterial and antioxidant potential.
TL;DR: In this paper , the authors tried to develop a scale consisting of the dimensions of service quality in the domestic airline industry in India, which has been experiencing a boom owing to the increasing number of passengers traveling by air.
Abstract: Providing quality service is an integral part of any airline’s efforts to increase profitability and cope with the growing aggressive competition that has emerged after the deregulation. To do this, the airlines must understand the requirements of their passengers and try to meet their expectations. This study tried to develop a scale consisting of the dimensions of service quality in the domestic airline industry in India, which has been experiencing a boom owing to the increasing number of passengers traveling by air. An extensive literature review was done, followed by empirical research conducted with the help of 384 questionnaires consisting of 28 items. The validity and reliability of the items were checked with KMO’s Bartlett’s test. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used for the study. The research established five dimensions of service quality known as EATRC (i.e., Employees, Assurance, Tangibles, Reliability, and Check-in) along with 23 sub-dimensions that depicted passengers’ perception of service quality. CFA was used to confirm the overall fitness of the model and validate the hypothesized relationships.
TL;DR: In this article , the authors reviewed the niche technologies like electrospinning, spraying, or mesoporous methods that led to the generation of more dissolvable antihypertensives.
Abstract: Most antihypertensive drugs have impaired dissolution rate and result from poorly aqueous solubility, polymorphic modifications, structure-based H-bond donor or acceptor anamolies. These physical attributes would have detrimental effects and may cause an entity out of the race from efficacious candidates. Nevertheless, compliance with the dissolution rate must be fulfilled under the regulatory mandate and serve as an assessment tool for product performance. The present reviews the niche technologies like electrospinning, spraying, or mesoporous methods that led to the generation of more dissolvable antihypertensives. Several drug delivery systems design allows the incorporation of surfactants, microenvironment dissolution rate modifiers, acidifiers that could improve the dissolution rate of antihypertensives are reviewed.
TL;DR: This is a case of a 49-year-old male alcoholic who developed severe breathlessness, desaturation, and loss of consciousness following an alcoholic bout found to be due to another rare viral pneumonia.
Abstract: This is a case of a 49-year-old male alcoholic who developed severe breathlessness, desaturation, and loss of consciousness following an alcoholic bout. Due to the ongoing COVID pandemic, he was suspected to be having COVID-19 infection. His clinical and radiological presentations were atypical for COVID-19. On investigations, it was found to be due to another rare viral pneumonia. The case is being reported due to its rarity.