Diabetes in the time of COVID-19 pandemic: A knife with two sharp ends

512-520Interactions of current pandemic COVID-19 and pre-existing major health burden Diabetes Mellitus have posed a serious global public health crisis. The emergence of COVID-19 as a communicable viral infection along with the presence of non-communicable diabetes, have transformed the health system into a knife with two sharp ends. Though diabetes worldwide is almost 20 times more than COVID-19 positive cases, the severe virulence and pathogenesis coincides with the routine treatment and pathogenesis of diabetes making it one of the most serious comorbid factors. The first three deaths due to COVID-19 reported in China were diabetes patients. The severity of the association of diabetes with COVID-19 ranges from 5 to 20%. Type 1 diabetes mellitus and type 2 diabetes mellitus increase the susceptibility to infections and their complications. The present study was attempted to review probable interaction between these two global health burdens and possible suggestive management to control their detrimental effect. An intensive online search was conducted using two databases, PubMed and Google Scholar. Most hypothesized pathways for COVID-19 infection are the ACE2 receptors and RAAS system followed by the DPP4 receptor pathway. This review proposes that proper and timely management of the COVD-19 patients with diabetes comorbidity might reduce COVID-19 disease burden

Sesame lignans as promising anti-inflammatory agent: Exploring novel therapeutic avenues with in silico and computational approach

Innumerable health-beneficial properties of sesame lignans like sesamol, sesamolin, sesamin and sesaminol make them lucrative agents in the pharmaceutical industry. To specify the mode of action of these phytochemicals, detailed computational physicochemical properties evaluation, and toxicity assessment (using free web servers and databases), as well as binding interactions with physiological inflammatory effectors (such as COX-2, TNF-α, IL-1β, IL-6) by means of rigid ligand-receptor docking (using software), have been thoroughly investigated. Interestingly, sesame lignans are conformed to have drug-likeness, indicating their efficacy and suitability like established therapeutics. These bioactive lignans possess drug-like attributes and effectively act as ligands in the present in-silico study. The basic pharmacokinetic profile of these compounds has suggested non-polar solvents or delivery systems for them to enhance their bioavailability in physiological systems. However, all the sesame lignans are toxic to the liver cells with a50 % lethal dose in the range of 500-1500 mg/kg. Toxicity study indicated minimum toxicity of lignans to normal cellular milieu, but noticeable cytotoxic effects against several cancerous cell lines suggesting their anti-carcinogenic properties. Finally, the findings of the molecular docking study have depicted a high affinity of these ligands for target proteins, even better than traditional anti-inflammatory drugs- Indomethacin and Ibuprofen. The molecular interactions have represented sesaminol as the most effective and Sesamol as the least potent ligand for target receptor whereas COX-2 seems to be the most vulnerable target. The docking scores varied widely (-4.7 to -11.0 kcal/mol). The present in-silico approach is expected to provide valuable resources for optimizing bioactive molecules as future-generation therapeutics before pre-clinical and clinical studies

Brexit or Brand it? The effects of attitude towards Brexit and reshored brands on consumer purchase intention

Brexit has caused a seismic shift in the British socio-economic and political landscapes, creating widespread uncertainties, while simultaneously giving hope and national pride to millions. The decision by a number of organizations to reshore their production has opened a new era for business management that challenges the axiomatic assumption of the benefits of offshored production. Although reshoring predates Brexit, the link between the two in the British context is not just serendipitous and they are argued to have reasonable interlinkages. However, there is inadequate empirical evidence to suggest that British consumers’ attitude towards Brexit has any effect on their intention to purchase reshored brands. Through a mixed-methods study comprising a survey of 415 respondents and 20 in-depth interviews, this paper addresses this research gap. Findings suggest that corporate social responsibility (CSR) and consumer reshoring sentiment (CRS) have positive effects on consumers’ attitude towards reshored brands. Despite CRS's positive influence on attitude towards Brexit, the latter does not have any significant effects on the intention to purchase a reshored brand, which is positively influenced by the attitude towards the same brand. As such, companies should enhance the image of their brands and CSR in order to harness the benefits of reshoring

Protective role of Ipomoea aquatica Forsk. crude extract on rat tissues in the presence of acephate and carbofuran by histopathology and cytometric determination

118-124Ipomoea aquatica Forsk., commonly called water spinach ( ‘kalmi’ in Bengali) is an underexploited local green leafy vegetable having enormous scope as a cheap antioxidant source. The study explores the ameliorative effect of aqueous I. aquatica extract (IAE) in acephate and carbofuran treated Wistar male rats. Aqueous IAE (@ 20 mg/kg body wt.), administered to rats treated with organophosphate acephate (@ 30 mg/kg body wt.) and carbamate carbofuran (@ 0.1 mg /kg body wt.), attenuated the cholinesterase activity in brain, liver and cellular blood and reformed the histological perturbations in the brain cortex as well as the kidney anomalies, to a good extent. The IAE also upregulated the NF-E2-related factor-2 (Nrf-2) and MnSOD gene expression against pesticide toxicity. Hence, results of the present study intervenes into a new approach of justifying the deleterious side effects of pesticides that are commonly used, and how green leafy vegetables can help ameliorate those harmful effects

Protective role of Ipomoea aquatica Forsk. crude extract on rat tissues in the presence of acephate and carbofuran by histopathology and cytometric determination

Ipomoea aquatica Forsk., commonly called water spinach ( ‘kalmi’ in Bengali) is an underexploited local green leafy vegetable having enormous scope as a cheap antioxidant source. The study explores the ameliorative effect of aqueous I. aquatica extract (IAE) in acephate and carbofuran treated Wistar male rats. Aqueous IAE (@ 20 mg/kg body wt.), administered to rats treated with organophosphate acephate (@ 30 mg/kg body wt.) and carbamate carbofuran (@ 0.1 mg /kg body wt.), attenuated the cholinesterase activity in brain, liver and cellular blood and reformed the histological perturbations in the brain cortex as well as the kidney anomalies, to a good extent. The IAE also upregulated the NF-E2-related factor-2 (Nrf-2) and MnSOD gene expression against pesticide toxicity. Hence, results of the present study intervenes into a new approach of justifying the deleterious side effects of pesticides that are commonly used, and how green leafy vegetables can help ameliorate those harmful effects

Modulation of inhibitory activity of xylanase - α-amylase inhibitor protein (XAIP): binding studies and crystal structure determination of XAIP- II from Scadoxus multiflorus at 1.2 Å resolution

Background: Plants produce a wide range of proteinaceous inhibitors to protect themselves against hydrolytic enzymes. Recently a novel protein XAIP belonging to a new sub-family (GH18C) was reported to inhibit two structurally unrelated enzymes xylanase GH11 and α -amylase GH13. It was shown to inhibit xylanase GH11 with greater potency than that of α-amylase GH13. A new form of XAIP (XAIP-II) that inhibits α-amylase GH13 with a greater potency than that of XAIP and xylanase GH11 with a lower potency than that of XAIP, has been identified in the extracts of underground bulbs of Scadoxus multiflorus. This kind of occurrence of isoforms of inhibitor proteins is a rare observation and offers new opportunities for understanding the principles of protein engineering by nature. Results: In order to determine the structural basis of the enhanced potency of XAIP-II against α-amylase GH13 and its reduced potency against xylanase GH11 as compared to that of XAIP, we have purified XAIP-II to homogeneity and obtained its complete amino acid sequence using cloning procedure. It has been crystallized with 0.1 M ammonium sulphate as the precipitating agent and the three-dimensional structure has been determined at 1.2 Å resolution. The binding studies of XAIP-II with xylanase GH11 and α-amylase GH13 have been carried out with surface plasmon resonance (SPR). Conclusion: The structure determination revealed that XAIP-II adopts the well known TIM barrel fold. The xylanase GH11 binding site in XAIP-II is formed mainly with loop α3-β3 (residues, 102 - 118) which has acquired a stereochemically less favorable conformation for binding to xylanase GH11 because of the addition of an extra residue, Ala105 and due to replacements of two important residues, His106 and Asn109 by Thr107 and Ser110. On the other hand, the α-amylase binding site, which consists of α-helices α6 (residues, 193 - 206), α7 (residues, 230 - 243) and loop β6-α6 (residues, 180 - 192) adopts a stereochemically more favorable conformation due to replacements of residues, Ser190, Gly191 and Glu194 by Ala191, Ser192 and Ser195 respectively in α-helix α6, Glu231 and His236 by Thr232 and Ser237 respectively in α-helix α7. As a result, XAIP-II binds to xylanase GH11 less favorably while it interacts more strongly with α-amylase GH13 as compared to XAIP. These observations correlate well with the values of 4.2 × 10-6 M and 3.4 × 10-8 M for the dissociation constants of XAIP-II with xylanase GH11 and α-amylase GH13 respectively and those of 4.5 × 10-7 M and 3.6 × 10-6 M of XAIP with xylanase GH11 and α-amylase GH13 respectively

Rapid immunochromatographic test: An evolving tool for diagnosis of scrub typhus

Background: Scrub typhus is prevalent in many districts of South Bengal throughout the year where an average temperature of 20–35°C, which contributes to the spread of Leptotrombidium deliense. However, its diagnosis remains complicated by the lack of readily available and validated assays, the non-specificity of clinical symptoms on admission, and even non-availability of the pathognomonic eschar in most of the cases. Aims and Objectives: This study was carried out to evaluate the rapid immunochromatographic test (RICT) for early detection of scrub typhus for using it as an early diagnostic tool at the field level. Materials and Methods: This cross-sectional study in which 181 serum samples from clinically suspected cases (after excluding dengue, malaria, Japanese encephalitis, and typhoid fever) collected over 13 months were processed for the detection of immunoglobulin M (IgM) antibodies for scrub typhus by enzyme-linked immunosorbent assay (ELISA) and rapid test. Results: Considering IgM ELISA for scrub typhus as the gold standard, the sensitivity, specificity, positive predictive value, and negative predictive value for RICT were found to be 100%, 86.87%, 50%, and 100%, respectively. Conclusion: RICT is a simple, rapid, and reliable assay for diagnosis of scrub typhus, capable of providing accurate results quickly and is highly suitable for field deployment in remote areas with limited medical support

<i style="mso-bidi-font-style:normal">Moringa oleifera </i>Lam. seed extract prevents fat diet induced oxidative stress in mice and protects liver cell-nuclei from hydroxyl radical mediated damage

794-802High fat diet (HFD) prompts metabolic pattern inducing  reactive oxygen species (ROS) production in mitochondria thereby triggering multitude of chronic disorders in human. Antioxidants from plant sources may be an imperative remedy against this disorder. However, it requires scientific validation. In this study, we explored if (i) Moringa oleifera seed extract (MoSE) can neutralize ROS generated in HFD fed mice; (ii)  protect cell-nuclei damage developed by Fenton reaction in vitro. Swiss mice were fed with HFD to develop oxidative stress model (HFD group). Other groups were control, seed extract alone treated, and MoSE simultaneously (HS) treated. Treatment period was of 15 days. Antioxidant enzymes with tissue nitrite content (TNC) and lipid peroxidation (LPO) were estimated from liver homogenate. HS group showed significantly higher (P <0.05)  superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH) activity, and ferric reducing antioxidant power (FRAP) compared to only HFD fed group. Further, TNC and LPO decreased significantly (P <0.05) in HS group compared to HFD fed group. MoSE also protected hepatocytes nuclei from the hydroxyl radicals generated by Fenton reaction. MoSE was found to be polyphenol rich with potent reducing power, free radicals and hydroxyl radicals scavenging activity. Thus, MoSE exhibited robust antioxidant prospective to neutralize ROS developed in HFD fed mice and also protected the nuclei damage from hydroxyl radicals. Hence, it can be used as herbal medication against HFD induced ROS mediated disorders

Sesame lignans as promising anti-inflammatory agent: Exploring novel therapeutic avenues with in silico and computational approach

547-559Innumerable health-beneficial properties of sesame lignans like sesamol, sesamolin, sesamin and sesaminol make them lucrative agents in the pharmaceutical industry. To specify the mode of action of these phytochemicals, detailed computational physicochemical properties evaluation, and toxicity assessment (using free web servers and databases), as well as binding interactions with physiological inflammatory effectors (such as COX-2, TNF-α, IL-1β, IL-6) by means of rigid ligand-receptor docking (using software), have been thoroughly investigated. Interestingly, sesame lignans are conformed to have drug-likeness, indicating their efficacy and suitability like established therapeutics. These bioactive lignans possess drug-like attributes and effectively act as ligands in the present in-silico study. The basic pharmacokinetic profile of these compounds has suggested non-polar solvents or delivery systems for them to enhance their bioavailability in physiological systems. However, all the sesame lignans are toxic to the liver cells with a50 % lethal dose in the range of 500-1500 mg/kg. Toxicity study indicated minimum toxicity of lignans to normal cellular milieu, but noticeable cytotoxic effects against several cancerous cell lines suggesting their anti-carcinogenic properties. Finally, the findings of the molecular docking study have depicted a high affinity of these ligands for target proteins, even better than traditional anti-inflammatory drugs- Indomethacin and Ibuprofen. The molecular interactions have represented sesaminol as the most effective and Sesamol as the least potent ligand for target receptor whereas COX-2 seems to be the most vulnerable target. The docking scores varied widely (-4.7 to -11.0 kcal/mol). The present in-silico approach is expected to provide valuable resources for optimizing bioactive molecules as future-generation therapeutics before pre-clinical and clinical studies

Quercetin and β-sitosterol prevent high fat diet induced dyslipidemia and hepatotoxicity in Swiss albino mice

60-66High fat diet group showed a significant rise in serum and hepatic total cholesterol, triglyceride and atherogenic index which are major biomarkers of dyslipidemia and cardiovascular risk. The liver function markers, lipid peroxidation and proinflammatory cytokine levels were elevated in high fat diet group whereas antioxidant levels significantly reduced. These findings manifest hepatic damage which was further confirmed by histological findings. Quercetin and β-sitosterol though structurally different yet both ameliorate the sickening changes in different mechanism. The current investigation is perhaps the first report of the mechanistic role of two polyphenols over dyslipidemia and subsequent hepatotoxicity