Netaji Subhas Chandra Bose Institute of Pharmacy

The estimation of sotagliflozin in tablet and bulk dose forms was accomplished by developing and validating an ultra-performance liquid chromatographic technique. A 2.1 x 50 mm, 1.7-micron BEH Waters UPLC column was used to do the chromatographic separation. The eluent was detected by UV at 225 nm using a mobile phase consisting of 70% acetonitrile and 30% OPA buffer (0.1% ortho-phosphoric acid) in isocratic mode. The approach was upheld and verified in accordance with the rules of the international conference on harmonization. The validation investigation confirmed the technique's accuracy and dependability. The retention time for sotagliflozin elution was 0.516 minutes. linearity was demonstrated in the concentration range of 10–50 μg/mL by the standard calibration curve for sotagliflozin. It was determined that the detection limit, or LOD, was 0.05 μg/mL, while the quantitation limit, or LOD, was 0.10 μg/mL. Stability was evidenced in the force degradation evaluation by the present approach. Empirical evidence has established that it is appropriate to estimate Sotagliflozin in both tablet and bulk dosage forms.

Central quadrant breast cancers pose a significant oncoplastic challenge. While conventional mastectomy and the Grisotti flap technique remain options, alternative approaches such as reverse batwing and perforator-based flaps offer additional possibilities for breast conservation. The Grisotti flap, despite its utility, has limitations, particularly in non-ptotic breasts, where it may lead to lateral fullness and suboptimal cosmesis. In this report, we describe the “Reverse Bay of Bengal” modification of the Grisotti flap, designed to address these limitations by preserving chest wall perforators and avoiding excessive lateral bulging. This technique offers an alternative for patients with centrally located tumors requiring nipple-areola complex (NAC) excision.

Diabetes is a chronic metabolic disorder that is characterized by high postprandial blood sugar levels and increased fasting, which disrupts physiological balance and causes organ damage. Owing to the global health risk of type 2 diabetes, natural remedies have shown promise as viable alternatives because of their outstanding antidiabetic properties. Nevertheless, the therapeutic use of these compounds is rather restricted due to their inadequate solubility, instability in the gastrointestinal tract, low absorption, and other related factors. Currently, the development of nanoscale systems is a notable approach to enhancing the delivery of phytochemicals. This study aims to investigate the advancements in drug delivery techniques using nanoparticles, with a particular focus on enhancing the effectiveness of herbal remedies in the treatment of diabetes. This study aims to enrich our understanding of nanotechnology's potential in enlightening drug delivery systems by employing database repositories like PubMed, Scopus, Google Scholar, and Web of Science. Based on their categorization and structure, nano-systems are classified into liposomes, nanostructured lipid carriers, phytosomes, niosomes, solid lipid nanoparticles, self-nano emulsifying drug delivery systems, and inorganic nano-carriers. This study intricately describes the formulation process, selection criteria, and mechanism of herb-loaded nanoparticles using an example of the pharmacokinetic and pharmacodynamic properties of antidiabetic herbal drugs. Researchers have proven that nanoformulations of herb-loaded antidiabetic drugs improve compliance and therapeutic efficacy by resolving pharmacokinetic and biopharmaceutical issues. We could expect the creation of nanoformulations to be a viable method for optimizing the therapeutic effectiveness of plant-produced antidiabetic compounds.

Abstract: Reports indicate a worldwide increase in the incidence of Early-Onset Colorectal Carcinoma (EOCRC) (<50 years old). In an effort to understand the different modes of pathogenesis in early-onset CRC, colorectal tumors from EOCRC (<50 years old) and Late-Onset patients (LOCRC; >50 years old) were screened to eliminate microsatellite instability (MSI), nuclear β-catenin, and APC mutations, as these are known canonical factors in CRC pathogenesis. Small-RNA sequencing followed by comparative analysis revealed differential expression of 23 miRNAs (microRNAs) specific to EOCRC and 11 miRNAs specific to LOCRC. We validated the top 10 EOCRC DEMs in TCGA-COAD and TCGA-READ cohorts, followed by validation in additional EOCRC and LOCRC cohorts. Our integrated analysis revealed upregulation of hsa-miR-1247-3p and hsa-miR-148a-3p and downregu-lation of hsa-miR-326 between the two subsets. Experimentally validated targets of the above miRNAs were compared with differentially expressed genes in the TCGA dataset to identify targets with physiological significance in EOCRC development. Our analysis revealed metabolic reprogramming, downregulation of anoikis-regulating pathways, and changes in tissue morphogenesis, potentially leading to anchorage-independent growth and progression of epithelial-mesenchymal transition (EMT). Upregulated targets include proteins present in the basal part of intestinal epithelial cells and genes whose expression is known to correlate with invasion and poor prognosis.

BACKGROUND Treatment of breast cancers with immunotherapy has so far achieved limited success. Traditional immunotherapies focusing on cytotoxic T cells have attained modest success, while the approval of phagocytic checkpoint blockers is still pending. Coagulation proteases are crucial elements pertaining to cancer growth and proliferation, but their relevance in altering the immunological topography in tumours remain largely uncharted. OBJECTIVE In this study, we aim to examine whether FVIIa-driven PAR2 activation and its subsequent signaling pathways assist cancer cells in evading phagocytic macrophages. METHODS PBMC/THP-1 derived macrophages were co-cultured with MDA MB-468 cells that were either pre-treated with or without FVIIa. The phagocytic activity of macrophages was assessed through flow cytometry and immunofluorescence. Additionally, we employed an allograft model using wild-type and PAR2 deleted 4T1 cells to investigate the impact of PAR2 activation on immune escape from macrophages in an in vivo setting. RESULTS Our key findings provide evidence that FVIIa-induced PAR2 cleavage ensues downstream signaling cascades thereby augmenting cellular miR-221 levels which transcriptionally enhances both CD47 and STC1 expression assisting the phagocytic escape from macrophages. STC1 dampens the surface expression of calreticulin (CRT), a dominant pro-phagocytic signal thereby tilting it in favour of phagocytic evasion. Mouse models using PAR2 depleted cells displayed lesser tumor volumes and corresponding greater phagocytic events when blended together with anti-CD47/PDL1 antibodies. CONCLUSION Conclusively we can summarize that PAR2 signaling initiates an intrinsic mechanism of immune escape by diminishing phagocytosis of cancer cells.

Mastalgia is a frequent and distressing symptom for many women, typically classified into cyclical and non-cyclical types. The Cardiff Breast Pain Chart offers a means to record daily mastalgia severity but does not account for variations during menstruation. The modified AIIMS chart, while including a visual analogue scale, uses multiple charts and lacks graphical integration. Here, we introduce the Kolkata Breast Pain Chart, a comprehensive tool combining a visual analogue scale, menstrual tracking, pain site identification, and bilateral recording. Integrating elements from previous models, it provides a unified approach for mastalgia documentation. A pilot study with 56 patients demonstrated an 80.35% compliance rate, showcasing its practical applicability.

The association between idiopathic venous thrombosis and occult cancer is widely recognized. However, the comprehensive understanding of how thrombin, generated during the process of thrombosis, possesses the potential to augment the malignant phenotype is still not well understood. The coagulation protease thrombin mediates its effects by cleaving protease-activated receptor 1 (PAR1), a receptor abundantly expressed on the surface of triple-negative breast cancer (TNBC) cells. While emerging evidence implicates coagulation proteases in facilitating cancer progression, the precise molecular pathways underlying thrombin-mediated induction of chemoresistance remain poorly defined. Here, we demonstrate that thrombin-induced PAR1 activation in TNBC cells promotes the development of a multidrug-resistant phenotype, mechanistically linked to the upregulation of the pro-survival protein MCL1. Genetic ablation of MCL1 sensitizes TNBC cells to cytotoxic drugs despite thrombin exposure, affirming MCL1's functional importance. Chromatin immunoprecipitation analyses reveal thrombin triggers protein kinase A-dependent phosphorylation of serine 133 residue of cAMP-responsive element-binding protein (CREB), enhancing CREB's affinity for the co-activators CBP and p300. Furthermore, thrombin treatment induces the nuclear translocation of CREB-regulated transcription coactivator 2 (CRTC2) in a calcium-dependent manner, which collectively interacts with CREB/CBP-P300. The coordinated action of these transcriptional co-activators facilitates the transcriptional induction of MCL1. We further report that PAR1 activation augments MCL1 binding to the deubiquitinase USP9X, reducing MCL1 turnover. Our pre-clinical breast cancer murine model also shows that genetic deletion of PAR1 sensitizes breast cancer cells to chemotherapeutic drugs in vivo. Collectively, these findings emphasize the thrombin-PAR1 axis as a novel driver of chemoresistance. Utilizing FDA-approved oral anticoagulants for selective blocking of thrombin action may serve as a potential therapeutic adjunct for the treatment of triple-negative breast cancer.

Ending a pregnancy is quite common these days. In developing countries, there are much more cases termed as unsafe abortion. Some standard drugs are already available in the market, most of them are possessing high level of toxicity and expensive. There is always search for a new drug which is safe and cost effective. Ageratina adenophora is a medicinal plant in the Asteraceae family. It mainly contains alkaloids. In this experiment, the study was focused on evaluating the abortifacient effect of Ageratina adenophora. The hydroalcoholic extract of the pods of Ageratina adenophora was formed by the maceration process. The extract has shown a promising effect as an abortion-inducing agent while compared with the standard drugs. The animals treated with the extract of Ageratina adenophorahas decreased the abortion time within 15.01 hrs with 85.22 percent fatality in offspring which is noteworthy. The research outcomes indicate that the hydroalcoholic extract of the pods of the Ageratina adenophora has shown significant abortifacient activity.

In the present research worka herbal formulation prepared from Kalmegh IP (Andrographis paniculata), containing andrographolide and choline chloride, was evaluated for its hepatoprotective activity on poultry chickens by using alcohol induced hepatotoxicity model. Ten days old poultry chicks were selected for the study where Silymarin was taken as the standard drug. After completion of the treatment (25 days), thiopentone sodium induced sleeping time, SGOT, SGPT, ALP, percentage increase in total body masswere evaluated and liver histology was conducted. The formulation showed significant hepatoprotective activity similar tothat ofstandard drug Silymarin.

MEDI5752 is a monovalent bispecific immunotherapy and is strategically unique as it combines both anti programmed cell death 1 and anti cytotoxic T-lymphocyte-associated protein 4 action. This is one of the first of this kind of molecule. The development of this molecule had been very interesting which is not usually described in regular clinical oncology journals thus losing an important piece of history of an upcoming subject. Only some phase I results in such development is published so far and no full report on this is available till now. This effort will try to record the facts and chain of events which actually occurred in inventing and bringing it in phase III trial.

In this study we have evaluated the preclinical observation of the Force Drop on the mature male albino rats. The Force Drop is the product of N. P. Dutt and Son, Kolkata, in this product have many herbal plants with their androgenic activity. Mainly we have compared this product with the activity of testosterone. We have used testosterone in this study as a standard drug or chemical. In this study we have grouped the all animals in 4 and each group has 6 animals, there are one untreated, treated with testosterone or standard group, another two groups are low dosed Force Drop treated group and last one is higher dosed Force Drop treated group. The study has shown that the animals of standard group increased the dry weight of androgen sensitivity tissues and overall body weight and the animals of treated groups or Force Drop Ptreated groups increased the dry weight of sensitivity tissues and overall body weight but lesser the testosterone treated group and more than untreated group. But the lower dosed Force Drop Ptreated group increased weight of androgen sensitivity tissues and body weight which are less than higher dosed Force Drop treated animal group and more than untreated group. And the higher dosed Force Drop treated animals group increased weight much more than the untreated group of animals and lower than standard group or testosterone treated group.

The leaves of Paederia foetida are commonly used in folk remedies to treat various types of wounds, especially burn wounds. The present study was carried out to evaluate the effect of hydroalcoholic extract of Paederia foetida on experimentally induced burn wound in rats and compare the effects with known wound healing agents, Silverex ointment and Aloe veragel. An appropriate gel formulation was chosen for topical application in this burn wound model. Animals treated with Paederia foetida leaves extract showed significant reduction in period of epithelialization and wound contraction 50% as compare to control and produced comparable effect as compare to Silverex ointment and Aloe vera gel. From the study It was concluded that Paederia foetida leaves extract applied topically (2.5% and 5% gel formulation) possesses burn wound healing activity.

Tecoma stans (L.) Juss.exKunth (Bignoniaceae) is mainly found in tropical and subtropical regions of Africa and Asia. The leaves, flowers, roots, and bark are used to treat various aliments includes, skin infections, kidney problems, intestinal disorders, jaundice, toothaches, joint pain and repair cracked bones, antidotes for snake, scorpion, and rat bites. The aim of the study is to assess the anti-arthritic properties of T. stans leaf using Complete Freund's adjuvant (CFA)-induced rat model. The ethanol extract of T. stans leaf (ETSL) was taken for Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS) analysis for the identification of potential bioactive. The in vitro antioxidant and anti-arthritic activity was studied at concentrations of 25, 50, 100, 200, 400, and 500 μg/ml. In vivo anti-arthritic activity was carried out by administering CFA (0.1 ml) into the sub-plantar surface of the right hind paw. The experimental animals were treated with indomethacin (10 mg/kg) and ETSL (250, 500 mg/kg) once a daily for fourteen days. The arthritic parameters such as paw thickness, arthritic index, arthritic score, body weight, organ weight, and hematological and biochemical parameters were evaluated. Pro-inflammatory cytokines; tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, anti-inflammatory cytokines; IL-4 and IL-10 and inflammatory mediator cyclooxygenase-2 (COX-2) were examined in blood serum. In vivo antioxidants parameters; superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and lipid peroxidation (LPO) was carried out in liver and joint. Radiological and histopathological analysis of joint was performed.A computational molecular docking investigation of the phytoconstituents was conducted against COX-2, IL-1β, IL-6, and TNF-α receptors by utilizing AutoDock 4.2 and BIOVIA-Discovery Studio Visualizer software. The in vitro result showed concentration dependent antioxidant activity with highest percentage of inhibition at 500 µg/ml. The in vivo result demonstrated significant restoration of arthritic parameters, hematological and biochemical indices and oxidative stress in CFA-induced rat which was further supported by radiological histological examination at ETSL 500 mg/kg. In addition, there was significant (p<0.05) reduction in pro-inflammatory cytokines, inflammatory mediators and up-regulation of anti-inflammatory cytokines was observed in the treated group. Verbascoside was found to exhibit better biding affinities -10.4, -7.4, -7 and -6.2 kcal/mol against COX-2, IL-1β, TNF-α, and IL-6 respectively, confirmed through in silico study. The observed outcome suggests that ETSL at a dosage of 500 mg/kg demonstrated notable anti-arthritic effects by suppressing pro-inflammatory cytokines and oxidative stress biomarkers. This effect could potentially be attributed to the presence of bioactive verbascoside identified in the LC-MS analysis.

La0.67Ca0.33MnOδ nanoparticles of approximate size ∼ 4 nm have been prepared by the chemical solution deposition method to investigate effect of oxygen stoichiometry in the nanoparticles without changing their sizes. Electrochemical oxidation method has been used to change the oxygen stoichiometry $\delta$δ at room temperature, which unlike conventional methods to change oxygen stoichiometry by heating in controlled ambience, does not lead to any significant change in size. This has allowed us to investigate the effects of stoichiometry variations in the nanoparticles with no change in size. The unit cell volume, lattice constants and orthorhombic strains of the as prepared sample (with $\delta$δ = 2.74) are changed by incorporation of oxygen by electrochemical oxidation which in turns affects the magnetic properties. In addition, oxidation leads to change in oxygen stoichiometry of the magnetically “dead” surface layer on the nanoparticles which also affects their magnetization and coercive field. Supplementary Information The online version contains supplementary material available at 10.1186/s11671-024-03969-y.