FORMULATION AND EVALUATION OF GLIMEPIRIDE-LOADED LIPOSOMES BY ETHANOLINJECTION METHOD

ABSTRACTObjective: The objective of present study deals with an attempt to formulate Glimepiride in liposomal drug delivery system, in order to maintainsteady state plasma concentration; hence it has to be administered frequently to the patients, because of its short plasma half life. To maintain steadyplasma concentration for longer period of time formulation of controlled drug release system is essential. Liposomal drug delivery system providessustained release of Glimepiride.Methods: Glimepiride liposomes were prepared by ethanol injection method using varying concentration of cholesterol and lecithin. Drug excipientcompatibility study was performed by FT-IR spectral studies and differential scanning calorimetry studies. Liposomes were evaluated for drugencapsulation efficiency, morphological study by optical microscope, SEM and TEM, vesicle size and zeta potential determination, In -vitro drugrelease & kinetic study and stability studies.Results: The formulations fulfilled all official requirements. The drug release was slow and sustained for >12 hrs. The formulations followed zeroorder kinetics. Zeta potential and stability study for 90 days demonstrated that the formulation was stable at 25¬¬¬¬oC than when refrigerated.Conclusion: Glimepiride was formulated as liposomal formulation after checking the compatibility by DSC and FT-IR studies. The liposomespreparation FA3 was optimized based on the particle size, zeta potential, entrapment efficiency, and drug release characteristics.Keywords: Liposomes, Antidiabetic, Glimepiride, Ethanol-injection method

Damage and yield loss estimate in maize varieties owing to stem borer (Chilo partellus Swinhoe) infestation and insecticidal control

Stem borer (Chilo partellus Swinhoe) is one of the most damaging and yield reducing pest in maize. Field experiments were organized to assess the extent of damage and yield loss due to the infestation of stem borer in maize following two factors randomized complete block design with three replications at National Maize Research Program, Rampur, Chitwan, Nepal, during two consecutive spring seasons of 2020 and 2021. Maize varieties; Rampur Hybrid (RH)-8, RH-10, RH-12 (CAH-1715), RH-14 (RML-86/RML-96), RH-16 (RML-95/RML-96), TX-369, Arun-2, ZM-401, ZM-627 and Rampur Composite were used as a test variety (First factor) whereas pest control conditions (spray and non-spray) was considered as the second factor in the experiments. The sprayed plots (protected plots) were kept completely free from stem borer infestation by using three application of standard dose of insecticide (spinosad 45% [email protected]/L) at 10 days interval and non spray (unprotected plots) were selected for natural infestation of stem borers. Standard agronomical practices such as time of planting, row spacing, seed rate, irrigation, weeding and fertilizer application and doses were adopted to raise the crop. Among tested varieties Arun-2 was found most susceptible to stem borer attack in both experimental years resulted in higher % dead hearts (6.04%), higher no of exit hole (4.72), higher % foliage damage at before tasseling stage (12.17%) and higher tunnel length (4.62cm). Quantitative yield loss increased with the increase of the borer's infestation. The yield loss was ranged from 25 to 45% in different maize varieties due to the attack of stem borer. Highest yield loss was quantified for the open pollinated varieties, ZM-401(44.61%) followed by Rampur Composite (41.39%) and Arun-2 (41.22%). Spraying of insecticide enabled the recently introduced maize hybrid RH-14 to produce more yield and to be less vulnerable to stem borer damage

Mcl-1 Inhibition Modulates ERK-Mediated Resistance in Multiple Myeloma

Novel multiple myeloma (MM) treatments have significantly improved over the previous several decades, primarily on account of targeting bone marrow microenvironment (BMM) pathways. However, drug resistance and patient relapse remain major clinical problems. The role of BMM in the upregulation of anti-apoptotic protein Mcl-1 is well documented. The Mcl-1 protein plays a critical role in the progression and acquired drug resistance in MM. The regulation of Mcl-1, a protein characterized by a short half-life, from transcription to degradation is crucial for understanding its role in cell survival. The GSK3β and Erk play important role in the stability of Mcl-1. Also, overexpression of phospho Erk is associated with the acquired resistance. In this study, we investigated Mcl-1 regulation, focusing on transcriptional and post-translational modifications and their impact on protein stability in Mcl-1 inhibitor ( KS18) treated cells. The small molecule inhibitor KS18 induces Mcl-1Ser159/Thr163 phosphorylation and ubiquitination resulting in a sharp decline in Mcl-1 protein levels. Furthermore, we assessed the effects of the KS18 in a combination with ERK inhibitors on cell viability and found that blocking the Mcl-1 stabilization mechanism improves the effectiveness and potency of KS18. Furthermore, we compared KS18 to different classes of chemotherapeutic agents, such as GSK3β/α inhibitor (LY209031), ERK inhibitor (SEH77272), MEK inhibitor (PD18435), and Akt inhibitor (AZD5363). Interestingly, we found KS18 more potent than other agents. Combined, our results propose a strong rationale for novel combination therapies using selective KS18 and ERK inhibitors, which have the potential to markedly improve the outcome of MM treatment. This may also address one of the major clinical problems, drug resistance, and enhance the use of existing drugs

Delivery and Evaluation of Participatory Education for Animal Keepers Led by Veterinarians and Para-Veterinarians around the Kanha Tiger Reserve, Madhya Pradesh, India.

<div><p>Aim</p><p>We aim to investigate local perceptions of animal health challenges; current animal health knowledge; and methods to provide effective, relevant education to animal keepers in the Kanha Tiger Reserve area.</p><p>Materials and methods</p><p>A farmer education programme was undertaken in the Kanha Tiger Reserve area. Local animal health priorities were investigated through participatory village meetings (n = 38), individual animal keeper questionnaires (n = 100) and a written survey of local paravets (n = 16). Educational interventions were: veterinary surgeon led education meeting (VE); paravet led education meeting (PVE); distribution of printed materials (PM). 230 village meetings were carried out across 181 villages, contacting 3791 animal keepers. 20 villages received printed materials. Information was gathered on perceptions of local animal health challenges and current remedies. Efficacy of knowledge transfer was assessed four to five months later using a purposeful sample of 38 villages.</p><p>Results</p><p>Group meetings identified ticks (35/38), foot and mouth disease (FMD) (31/38) and diarrhoea (30/38) as the greatest animal health challenges. Individual interviews identified haemorrhagic septicaemia (HS) (87/100), blackquarter (BQ) (66/100) and plastic ingestion (31/100). Paravets identified FMD (7/16), BQ (6/16) and HS (6/16), and also indicated that animal husbandry and socio-economic factors were important. Current treatments were primarily home remedies and herbalism, but also included contacting a paravet, use of pharmaceuticals and faith healing. Animal treatment knowledge prior to intervention was not significantly different between groups (P = 0.868). Following intervention animal health knowledge was assessed: PVE performed better than controls (P = 0.001) and PM (P = 0.003); VE performed better than controls (P = 0.009). There was no significant difference between VE and PVE (P = 0.666) nor PM and controls (P = 0.060).</p><p>Conclusions and recommendations</p><p>Open access participatory village meetings are an effective way to provide animal health education. In this region distribution of posters and leaflets did not appear to be an effective way to contact animal keepers. Meetings led by paravets can be as effective as those led by veterinarians and paravets can rapidly and sustainably contact large numbers of animal keepers. Investigation of the local animal health situation is essential to ensure education is relevant and accessible to intended recipients. Interventions must be carefully planned to maximise engagement of all sections of the community, particularly women.</p></div

Development of Novel Dual Inhibitor of Chemokine Receptor 4 and Mcl-1 Against Multiple Myeloma

Multiple myeloma (MM) is a neoplastic plasma-cell disorder. This is characterized by clonal proliferation of malignant plasma cells in the bone-marrow (BM) microenvironment, monoclonal protein in blood or urine, and associated organ dysfunction. The treatment options approved by FDA are immune-modulatory agents, proteasome inhibitors, and autologous stem cell transplantation (ASCT). Unfortunately, MM remains uniformly fatal owing to intrinsic or acquired drug resistance and the median survival time is 3 to 5 years. Thus, there is a great need for novel strategies to combat MM. The intimate relationship of myeloma cells to BM microenvironment is “hallmark of myeloma”. The homing of MM cells to the BM, mediated by the chemokine stromal cell-derived factor-1α (SDF-1α) and its receptor CXCR4 has important functional sequelae. The BM microenvironment constituting cells secrete chemokines, cytokines, and growth factors such as interleukin 6 (IL6), vascular endothelial growth factor (VEGF), SDF-1α, and tumor necrosis factor α (TNFα) etc. These growth factors either secreted by MM or BM microenvironment cells (e.g. stromal cells) contribute in activation of several signaling pathways including nuclear factor-κB (NF-κB); phosphatidylinositol 3-kinase (PI3K)-Akt; Ras-Raf-MAPK kinase (MEK)-extracellular signal regulated kinase (ERK); and the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3). Activation of these pathways has been associated with increased expression of several anti-apoptotic proteins such as Bcl-2, Bcl-xL, Mcl-1, and XIAP. Collectively, these discoveries highlight that interaction of MM cells to BM microenvironment not only promote growth, survival and migration of MM cells, but also confer resistance to conventional chemotherapy. We hypothesized that an agent capable of inhibiting the migration of myeloma cells to bone marrow and suppressing the expression of survival protein Mcl-1 would be a better option for MM treatment.We have synthesized a novel dual inhibitor of CXCR4 and Mcl-1. Our data suggests that this molecule inhibits the expression of CXCR4 and Mcl-1 and survival of MM cells

Past, Present, and a Glance into the Future of Multiple Myeloma Treatment.

Multiple myeloma (MM) is a challenging hematological cancer which typically grows in bone marrow. MM accounts for 10% of hematological malignancies and 1.8% of cancers. The recent treatment strategies have significantly improved progression-free survival for MM patients in the last decade; however, a relapse for most MM patients is inevitable. In this review we discuss current treatment, important pathways for proliferation, survival, immune suppression, and resistance that could be targeted for future treatments

Role of nutrients in wheat: a review

Wheat (Triticum aestivum L.) is an important cereal crop that provides ample nutritious calories for humans and animals. The nutrient plays a vital role in the production of wheat. In this review, previous works were evaluated to investigate the role of nutrients, nutrient deficiency and toxicity in wheat. Both macro and micronutrients are necessary for wheat plants. Every nutrient has its own character and is involved in different metabolic processes of plant life. Nutrient deficiency and toxicity conditions inhibit normal plant growth and exhibit characteristic symptoms. For optimal growth, development, and production, plants need all the necessary nutrients in balance. A balanced application of the primary nutrients (N, P, K), secondary nutrient (S) and some other micronutrients (Zn, B) are needed to enhance wheat production. The soil tests and the demand for crop nutrients should be assessed to identify the quantity of fertilizer recommended for the crop. This study would be a valuable means to wheat growers and researchers for sustainable and higher wheat production

Discovering Potential in Non-Cancer Medications: A Promising Breakthrough for Multiple Myeloma Patients.

Multiple myeloma (MM) is a common type of cancer that unfortunately leads to a significant number of deaths each year. The majority of the reported MM cases are detected in the advanced stages, posing significant challenges for treatment. Additionally, all MM patients eventually develop resistance or experience relapse; therefore, advances in treatment are needed. However, developing new anti-cancer drugs, especially for MM, requires significant financial investment and a lengthy development process. The study of drug repurposing involves exploring the potential of existing drugs for new therapeutic uses. This can significantly reduce both time and costs, which are typically a major concern for MM patients. The utilization of pre-existing non-cancer drugs for various myeloma treatments presents a highly efficient and cost-effective strategy, considering their prior preclinical and clinical development. The drugs have shown promising potential in targeting key pathways associated with MM progression and resistance. Thalidomide exemplifies the success that can be achieved through this strategy. This review delves into the current trends, the challenges faced by conventional therapies for MM, and the importance of repurposing drugs for MM. This review highlights a noncomprehensive list of conventional therapies that have potentially significant anti-myeloma properties and anti-neoplastic effects. Additionally, we offer valuable insights into the resources that can help streamline and accelerate drug repurposing efforts in the field of MM