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Transplanting islets serves best option for restoring lost beta cell mass and function. Small bio-chemical agents do have the potential to generate new islets mass, however lack of understanding about mechanistic action of these small molecules eventually restricts their use in cell-based therapies for diabetes. We recently reported \"Swertisin\" as a novel islet differentiation inducer, generating new beta cells mass more effectively. Henceforth, in the present study we attempted to investigate the molecular signals that Swertisin generate for promoting differentiation of pancreatic progenitors into islet cells. To begin with, both human pancreatic progenitors (PANC-1 cells) and primary cultured mouse intra-islet progenitor cells (mIPC) were used and tested for Swertisin induced islet neogenesis mechanism, by monitoring immunoblot profile of key transcription factors in time dependent manner. We observed Swertisin follow Activin-A mediated MEPK-TKK pathway involving role of p38 MAPK via activating Neurogenin-3 (Ngn-3) and Smad Proteins cascade. This MAP Kinase intervention in differentiation of cells was confirmed using strong pharmacological inhibitor of p38 MAPK (SB203580), which effectively abrogated this process. We further confirmed this mechanism in-vivo in partial pancreatectomised (PPx) mice model, where we could show Swertisin exerted potential increase in insulin transcript levels with persistent down-regulation of progenitor markers like Nestin, Ngn-3 and Pancreatic Duodenal Homeobox Gene-1 (PDX-1) expression, within three days post PPx. With detailed molecular investigations here in, we first time report the molecular mode of action of Swertisin for islet neogenesis mediated through MAP Kinase (MEPK-TKK) pathway involving Ngn-3 and Smad transcriptional regulation. These findings held importance for developing Swertisin as potent pharmacological drug candidate for effective and endogenous differentiation of islets in cell based therapy for diabetes.

Cell surface protein, CD20, is extensively expressed on the surface of B cells. Antibodies targeting CD20 protein are being used to treat B-cell malignancies and B-cell mediated autoimmune diseases. Considering the cost of therapy with innovator monoclonal antibodies for these diseases, development of biosimilar products for the treatment of such diseases provides affordable solution to rising healthcare costs. Reference products of rituximab (six batches) were procured and stored as per manufacturer's instructions. Cell lines used in bioassay were procured from American Type Culture Collection and all other reagents used for analysis were of analytical grade. Primary structure was studied by intact mass analysis, peptide fingerprinting, peptide mass fingerprinting and sequence coverage analysis. Higher order structure was studied by circular dichroism, ultraviolet-visible spectroscopy, fluorescence spectroscopy, and disulfide bridge analysis. Different isoforms of reference product and SB-02 were identified using capillary isoelectric focusing and capillary zone electrophoresis. Glycosylation was studied by N-glycan mapping using LC-ESI-MS, point of glycosylation, released glycan analysis using ultra performance liquid chromatography (UPLC). Product related impurities such as oligomer content analysis and oxidized impurities were studied using size exclusion chromatography and reverse phase high performance liquid chromatography, respectively. Here, we report physicochemical and biological characterizations of Sun Pharma's proposed biosimilar (SB-02) to rituximab, a monoclonal anti-CD20 antibody approved for the treatment of non-Hodgkin's lymphoma and chronic lymphocytic leukemia. SB-02 and rituximab exhibited indistinguishable primary as well as higher-order structure upon analyzing with the array of analytical and extended characterization methods according to statistical methods. The molecule also displayed comparability to reference product in post-translational modifications and charge heterogeneity. In functional bioassays, SB-02 demonstrated comparable potency with respect to reference product. Our results indicate highly similar quality profile between SB-02 and rituximab.

Blood transfusion has been used as an emergency and life-saving step, since many years in human as well as animals medicine. The objective of this study was to demonstrate the effectiveness of whole blood transfusion in treatment of anaemic dogs. A total of ten anaemic dogs were given whole blood transfusion as part of therapy. Four dogs were suffering from hemolytic anaemia, three were suffering from severe haemorrhagic gastroenteritis and etiology was not known in three cases. Donors selected were overall healthy, negative for haemoprotozoan parasite on blood smear examination, between the ages of 1-6 years with no history of recent disease and are not currently on any medications. Major and minor cross matching tests were done between donor and recipient. Amount of blood to be transfused was calculated by formula 90 ml x kg body weight (BW) x ([desired packed cell volume (PCV) - patient PCV]/ PCV of donor blood). Rate of transfusion was 1ml/kg/hour at start for the first 30 minutes and then 3 ml/kg/hour for the rest duration of the transfusion. Transfusion was completed within 4-6 hours. There was significant improvement in mean haemoglobin and PCV values before and after treatment. Nine dogs survived after blood transfusion without any adverse reactions while one collapsed after 4 days of transfusion from severe clinical complications.

Aim. Stem cell therapy is one of the upcoming therapies for the treatment of diabetes. Discovery of potent differentiating agents is a prerequisite for increasing islet mass. The present study is an attempt to screen the potential of novel small biomolecules for their differentiating property into pancreatic islet cells using NIH3T3, as representative of extra pancreatic stem cells/progenitors. Methods. To identify new agents that stimulate islet differentiation, we screened various compounds isolated from Enicostemma littorale using NIH3T3 cells and morphological changes were observed. Characterization was performed by semiquantitative RT-PCR, Q-PCR, immunocytochemistry, immunoblotting, and insulin secretion assay for functional response in newly generated islet-like cell clusters (ILCC). Reversal of hyperglycemia was monitored after transplanting ILCC in STZ-induced diabetic mice. Results. Among various compounds tested, swertisin, an isolated flavonoid, was the most effective in differentiating NIH3T3 into endocrine cells. Swertisin efficiently changed the morphology of NIH3T3 cells from fibroblastic to round aggregate cell cluster in huge numbers. Dithizone (DTZ) stain primarily confirmed differentiation and gene expression studies signified rapid onset of differentiation signaling cascade in swertisin-induced ILCC. Molecular imaging and immunoblotting further confirmed presence of islet specific proteins. Moreover, glucose induced insulin release (in vitro) and decreased fasting blood glucose (FBG) (in vivo) in transplanted diabetic BALB/c mice depicted functional maturity of ILCC. Insulin and glucagon expression in excised islet grafts illustrated survival and functional integrity. Conclusions. Rapid induction for islet differentiation by swertisin, a novel herbal biomolecule, provides low cost and readily available differentiating agent that can be translated as a therapeutic tool for effective treatment in diabetes.

Plants, being sessile, are continuously exposed to varietal environmental stressors, which consequently induce various bio-physiological changes in plants that hinder their growth and development. Oxidative stress is one of the undesirable consequences in plants triggered due to imbalance in their antioxidant defense system. Biochemical studies suggest that nanoparticles are known to affect the antioxidant system, photosynthesis, and DNA expression in plants. In addition, they are known to boost the capacity of antioxidant systems, thereby contributing to the tolerance of plants to oxidative stress. This review study attempts to present the overview of the role of nanoparticles in plant growth and development, especially emphasizing their role as antioxidants. Furthermore, the review delves into the intricate connections between nanoparticles and plant signaling pathways, highlighting their influence on gene expression and stress-responsive mechanisms. Finally, the implications of nanoparticle-assisted antioxidant strategies in sustainable agriculture, considering their potential to enhance crop yield, stress tolerance, and overall plant resilience, are discussed.

The genus Eucalyptus is a globally captivated source of hardwood and is well known for its medicinal uses. The hybrid and wild species of Eucalyptus are widely used as exotic plantations due to their renowned potential of adapting to various systems and sites, and rapid large-scale propagation of genetically similar plantlets, which further leads to the extensive propagation of this species. Tissue culture plays a crucial role in the preservation, propagation, and genetic improvement of Eucalyptus species. Despite unquestionable progression in biotechnological and tissue culture approaches, the productivity of plantations is still limited, often due to the low efficiency of clonal propagation from cuttings. The obtained F1 hybrids yield high biomass and high-quality low-cost raw material for large-scale production; however, the development of hybrid, clonal multiplication, proliferation, and post-developmental studies are still major concerns. This riveting review describes the problems concerning the in vitro and clonal propagation of Eucalyptus plantation and recent advances in biotechnological and tissue culture practices for massive and rapid micropropagation of Eucalyptus, and it highlights the Eucalyptus germplasm preservation techniques.

India is a multilingual country. Hindi is the national language of India and Devanãgri script is used to write Hindi language. Various documents with legal value are made in Devanãgri script, which may be questioned for their authenticity and authorship. Sufficient research has been done and reported about different scripts. However, researches based on Devanãgri script are limited. This study focuses on finding the significant class characteristics of writers from three different states of India, namely, Bihar, Madhya Pradesh and Punjab. The data was also statistically analysed using Pearson's Chi-Square test for its significance. Handwriting samples from 300 subjects were collected from three different states of India to analyze various class characteristics in Devanãgri script. The samples were examined qualitatively and statistically. Various general characteristics were selected for the analysis and characteristic features were tabulated after qualitative examination. Statistical analysis showed that the data was statistically significant. The general characteristics selected for the analysis and comparison of the handwriting samples in Devanãgri script were found to be significant. The impact of regional scripts on the Devanãgri script should be performed, as the influence of regional language could be seen in the samples collected from Punjab.

The genus Eucalyptus is a globally captivated source of hardwood and is well known for its medicinal uses. The hybrid and wild species of Eucalyptus are widely used as exotic plantations due to their renowned potential of adapting to various systems and sites, and rapid large-scale propagation of genetically similar plantlets, which further leads to the extensive propagation of this species. Tissue culture plays a crucial role in the preservation, propagation, and genetic improvement of Eucalyptus species. Despite unquestionable progression in biotechnological and tissue culture approaches, the productivity of plantations is still limited, often due to the low efficiency of clonal propagation from cuttings. The obtained F1 hybrids yield high biomass and high-quality low-cost raw material for large-scale production; however, the development of hybrid, clonal multiplication, proliferation, and post-developmental studies are still major concerns. This riveting review describes the problems concerning the in vitro and clonal propagation of Eucalyptus plantation and recent advances in biotechnological and tissue culture practices for massive and rapid micropropagation of Eucalyptus, and it highlights the Eucalyptus germplasm preservation techniques.