The Paradigm shift from Conventional Mythology to the Vortex of Feminist ideology in Githa Hariharan’s The Thousand Faces of the Night

Githa Hariharan (born in 1954) is primarily known for her novel, The Thousand Faces of Night. She won the Commonwealth Writer's Prize for Best First Novel. But here she reveals herself as a master of the short narrative as well. The second published literary works of the renowned Indian English writer, The Art of Dying (1993) won wide applause for its relevant and bold theme. She is also a social activist who portrays social issues in her literary works. She belongs to the new generation of Indian writers who have earned greater visibility and readership for Indian English Literature. As a writer she is preoccupied with human condition which to her is the pre-requisite and the essence of creative writing in general and of literature in particular. Apparently, she chooses a small space for almost all her novels but endeavors to enlarge the limited space to such an extent that it becomes an elaborate presentation of human condition. Hariharan believes in inclusiveness, which extends and broadens an individual's social horizon. She thinks that writers have a socio‑political responsibility as well

A comparative study of efficacy and safety of anti-oxidants as an add-on therapy to metformin on glycemic parameters in newly diagnosed type 2 diabetes mellitus patients at a tertiary care hospital

Background: Oxidative stress plays major role in diabetes mellitus (DM), abnormal high free radicals decline antioxidant defence mechanism can lead to damage of cellular organelles and enzymes, increased lipid peroxidation and insulin resistance leads to development of complications. Supplementation of antioxidants protects free radical induced damage and further complications. The objective was to evaluate the efficacy and safety of metformin versus metformin with vitamin C and E on glycaemic parameters in newly diagnosed type 2 diabetes mellitus (T2DM).Methods: 60 newly diagnosed T2DM patients were randomized into two groups of 30 in each to receive metformin (500 mg BD) alone in group A versus metformin (500 mg BD)+vitamin C (500 mg OD)+vitamin E (400 mg OD) in group B for 12 weeks. Efficacy was measured by improvement in glycaemic (FBS fasting blood sugar, PPBS postprandial blood sugar and HbA1c glycosylated haemoglobin) parameters at week 4, 8 and 12 from baseline. Safety was assessed by monitoring treatment emergent adverse effects.Results: The baseline characteristics were comparable between the two groups. There was a significant reduction of glycaemic parameters seen in both the groups from baseline to week 12 (p0.05). No significant adverse effects were noted.Conclusions: Both the groups are effective in improving glycaemic indices and supplementation of vitamins along with metformin as compared to metformin alone with no significant adverse effect. Hence, daily consumption of vitamins may be beneficial in decreasing blood glucose in patients with T2DM and thus reducing the risk of complications

Peripherally restricted oxytocin is sufficient to reduce food intake and motivation, while <scp>CNS</scp> entry is required for locomotor and taste avoidance effects

ObjectivesOxytocin (OT) has a well‐established role in reproductive behaviours; however, it recently emerged as an important regulator of energy homeostasis. In addition to central nervous system (CNS), OT is found in the plasma and OT receptors (OT‐R) are found in peripheral tissues relevant to energy balance regulation. Here, we aim to determine whether peripheral OT‐R activation is sufficient to alter energy intake and expenditure.Methods and ResultsWe first show that systemic OT potently reduced food intake and food‐motivated behaviour for a high‐fat reward in male and female rats. As it is plausible that peripherally, intraperitoneally (IP) injected OT crosses the blood‐brain barrier (BBB) to produce some of the metabolic effects within the CNS, we screened, with a novel fluorescently labelled‐OT (fAF546‐OT, Roxy), for the presence of IP‐injected Roxy in CNS tissue relevant to feeding control and compared such with BBB‐impermeable fluorescent OT‐B$_{12}$ (fCy5‐OT‐B$_{12;}$ BRoxy). While Roxy did penetrate the CNS, BRoxy did not. To evaluate the behavioural and thermoregulatory impact of exclusive activation of peripheral OT‐R, we generated a novel BBB‐impermeable OT (OT‐B$_{12}$), with equipotent binding at OT‐R in vitro. In vivo, IP‐injected OT and OT‐B$_{12}$ were equipotent at food intake suppression in rats of both sexes, suggesting that peripheral OT acts on peripheral OT‐R to reduce feeding behaviour. Importantly, OT induced a potent conditioned taste avoidance, indistinguishable from that induced by LiCl, when applied peripherally. Remarkably, and in contrast to OT, OT‐B$_{12}$ did not induce any conditioned taste avoidance. Limiting the CNS entry of OT also resulted in a dose‐dependent reduction of emesis in male shrews. While both OT and OT‐B$_{12}$ proved to have similar effects on body temperature, only OT resulted in home‐cage locomotor depression.ConclusionsTogether our data indicate that limiting systemic OT CNS penetrance preserves the anorexic effects of the peptide and reduces the clinically undesired side effects of OT: emesis, taste avoidance and locomotor depression. Thus, therapeutic targeting of peripheral OT‐R may be a viable strategy to achieve appetite suppression with better patient outcomes

A Novel Role for IκBζ in the Regulation of IFNγ Production

IκBζ is a novel member of the IκB family of NFκB regulators, which modulates NFκB activity in the nucleus, rather than controlling its nuclear translocation. IκBζ is specifically induced by IL-1β and several TLR ligands and positively regulates NFκB-mediated transcription of genes such as IL-6 and NGAL as an NFκB binding co-factor. We recently reported that the IL-1 family cytokines, IL-1β and IL-18, strongly synergize with TNFα for IFNγ production in KG-1 cells, whereas the same cytokines alone have minimal effects on IFNγ production. Given the striking similarities between the IL-1R and IL-18R signaling pathways we hypothesized that a common signaling event or gene product downstream of these receptors is responsible for the observed synergy. We investigated IκBζ protein expression in KG-1 cells upon stimulation with IL-1β, IL-18 and TNFα. Our results demonstrated that IL-18, as well as IL-1β, induced moderate IκBζ expression in KG-1 cells. However, TNFα synergized with IL-1β and IL-18, whereas by itself it had a minimal effect on IκBζ expression. NFκB inhibition resulted in decreased IL-1β/IL-18/TNFα-stimulated IFNγ release. Moreover, silencing of IκBζ expression led to a specific decrease in IFNγ production. Overall, our data suggests that IκBζ positively regulates NFκB-mediated IFNγ production in KG-1 cells

IFNγ and IL-12 restrict Th2 responses during Helminth/Plasmodium co-infection and promote IFNγ from Th2 cells

Parasitic helminths establish chronic infections in mammalian hosts. Helminth/Plasmodium co-infections occur frequently in endemic areas. However, it is unclear whether Plasmodium infections compromise anti-helminth immunity, contributing to the chronicity of infection. Immunity to Plasmodium or helminths requires divergent CD4+ T cell-driven responses, dominated by IFNγ or IL-4, respectively. Recent literature has indicated that Th cells, including Th2 cells, have phenotypic plasticity with the ability to produce non-lineage associated cytokines. Whether such plasticity occurs during co-infection is unclear. In this study, we observed reduced anti-helminth Th2 cell responses and compromised anti-helminth immunity during Heligmosomoides polygyrus and Plasmodium chabaudi co-infection. Using newly established triple cytokine reporter mice (Il4gfpIfngyfpIl17aFP635), we demonstrated that Il4gfp+ Th2 cells purified from in vitro cultures or isolated ex vivo from helminth-infected mice up-regulated IFNγ following adoptive transfer into Rag1-/- mice infected with P. chabaudi. Functionally, Th2 cells that up-regulated IFNγ were transcriptionally re-wired and protected recipient mice from high parasitemia. Mechanistically, TCR stimulation and responsiveness to IL-12 and IFNγ, but not type I IFN, was required for optimal IFNγ production by Th2 cells. Finally, blockade of IL-12 and IFNγ during co-infection partially preserved anti-helminth Th2 responses. In summary, this study demonstrates that Th2 cells retain substantial plasticity with the ability to produce IFNγ during Plasmodium infection. Consequently, co-infection with Plasmodium spp. may contribute to the chronicity of helminth infection by reducing anti-helminth Th2 cells and converting them into IFNγ-secreting cells

Antimetastatic activity of tinospora cordifolia involves inhibition of cell migration and invasion regulated by twist and snail genes

VEGF-mediated signalling facilitates survival and metastasis of tumour cells. The metastatic cascade follows tumour cell dissemination, passage through the blood and/or lymphatic system, and colonisation at a distant site. Increased cell motility of cancer cells at the leading tumour edge has been attributed to the epithelial mesenchymal transition (EMT) which facilitates their release and invasiveness. Breast cancers which exhibit properties of EMT are highly aggressive and resistant to therapy. In the present study, two molecules from hexane and methanolfractions (T1 and T2)from the plant Tinospora cordifoliawere chosen to verify the anti-metastatic activity. Our data show that inMCF-7 cells,T1 treatment significantly suppressed the proliferation, migration and invasion of MCF-7cells when compared to that of T2. EMT-related genes, Twist and Snail, were downregulated by T1 with increased transcription of E-cadherin. Overall, our results demonstrate that T1 down-regulates Twist and Snail genes involvedin proliferation, migration and invasion

Functional Consequences of CFTR Interactions in Cystic Fibrosis

Cystic fibrosis (CF) is a fatal autosomal recessive disorder caused by the loss of function mutations within a single gene for the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). CFTR is a chloride channel that regulates ion and fluid transport across various epithelia. The discovery of CFTR as the CF gene and its cloning in 1989, coupled with extensive research that went into the understanding of the underlying biological mechanisms of CF, have led to the development of revolutionary therapies in CF that we see today. The highly effective modulator therapies have increased the survival rates of CF patients and shifted the epidemiological landscape and disease prognosis. However, the differential effect of modulators among CF patients and the presence of non-responders and ineligible patients underscore the need to develop specialized and customized therapies for a significant number of patients. Recent advances in the understanding of the CFTR structure, its expression, and defined cellular compositions will aid in developing more precise therapies. As the lifespan of CF patients continues to increase, it is becoming critical to clinically address the extra-pulmonary manifestations of CF disease to improve the quality of life of the patients. In-depth analysis of the molecular signature of different CF organs at the transcriptional and post-transcriptional levels is rapidly advancing and will help address the etiological causes and variability of CF among patients and develop precision medicine in CF. In this review, we will provide an overview of CF disease, leading to the discovery and characterization of CFTR and the development of CFTR modulators. The later sections of the review will delve into the key findings derived from single-molecule and single-cell-level analyses of CFTR, followed by an exploration of disease-relevant protein complexes of CFTR that may ultimately define the etiological course of CF disease