Prevalence of smoking in rural and urban areas in India: Systematic review

The use of tobacco overall in India is given with an advanced rate of frequency of smoking. The high burden of tobacco use, the studies have stated the examined the indigenous, socioeconomic, demographic, and, other factors of smoking, smokeless tobacco in India. The main idea is to study the burden of the complaint, socioeconomic status, demographic of the use of smoking in civic and pastoral places of overall India. The studies have analysed it through a cross-sectional bivariate and multivariate analysis, for representation of the sample of individualities from the Global Adult Tobacco Survey in India. The different forms of tobacco use are in three different forms, substantially smoking only, smokeless tobacco use, and admixture of both uses were considered as outgrowth variables of all the studies. Smokeless tobacco use was the major form of tobacco use in India followed by smoking and binary tobacco use. Tobacco use is in advanced among males than in ladies in the pastoral and civic populations of India. The population was lacking knowledge of the health hazards of tobacco and had an advanced frequency of tobacco use in each form.&nbsp

Interaction between cibacron blue F3GA and Luteinizing hormone: a chromatographic investigation

Luteinizing hormone which was bound to Cibacron Blue F3GA could not be eluted with 10mM NAD. Bound LH could be eluted partially (up to 5%) with 80% ethylene glycol and rest with 50mM phosphate buffer pH 7.5 containing 1M NaCl. Each of the bound fractions could also be sub-fractionated with differential elution with a gradient of ethylene glycol or NaCl. This indicated that pituitary LH was a mixture of two different sub-populations of LH, one which interacts with CB predominantly via hydrophobic interactions and the other via electrostatic interaction. In the case of subunits of LH that occur in free state in pituitaries, approximately half of the bound subunits interacted with CB column predominantly via hydrophobic interactions whereas the other half interacted via electrostatic force. It is concluded that differences in glycan content, composition and structure could be the cause for differential binding of buLH and its free subunits to the CBA column

Optimizing a therapeutic humanized follicle-stimulating hormone-blocking antibody formulation by protein thermal shift assay

Biopharmaceutical products are formulated using several Food and Drug Administration (FDA) approved excipients within the inactive ingredient limit to maintain their storage stability and shelf life. Here, we have screened and optimized different sets of excipient combinations to yield a thermally stable formulation for the humanized follicle-stimulating hormone (FSH)-blocking antibody, MS-Hu6. We used a protein thermal shift assay in which rising temperatures resulted in the maximal unfolding of the protein at the melting temperature (T ). To determine the buffer and pH for a stable solution, four different buffers with a pH range from 3 to 8 were screened. This resulted in maximal T s at pH 5.62 for Fab in phosphate buffer and at pH 6.85 for Fc in histidine buffer. Upon testing a range of salt concentrations, MS-Hu6 was found to be more stable at lower concentrations, likely due to reduced hydrophobic effects. Molecular dynamics simulations revealed a higher root-mean-square deviation with 1 mM than with 100 mM salt, indicating enhanced stability, as noted experimentally. Among the stabilizers tested, Tween 20 was found to yield the highest T and reversed the salt effect. Among several polyols/sugars, trehalose and sucrose were found to produce higher thermal stabilities. Finally, binding of recombinant human FSH to MS-Hu6 in a final formulation (20 mM phosphate buffer, 1 mM NaCl, 0.001% w/v Tween 20, and 260 mM trehalose) resulted in a thermal shift (increase in T ) for the Fab, but expectedly not in the Fc domain. Given that we used a low dose of MS-Hu6 (1 μM), the next challenge would be to determine whether 100-fold higher, industry-standard concentrations are equally stable

FSH-blocking therapeutic for osteoporosis

Pharmacological and genetic studies over the past decade have established the follicle-stimulating hormone (FSH) as an actionable target for diseases affecting millions, namely osteoporosis, obesity, and Alzheimer\u27s disease. Blocking FSH action prevents bone loss, fat gain and neurodegeneration in mice. We recently developed a first-in-class, humanized, epitope-specific FSH-blocking antibody, MS-Hu6, with a K of 7.52 nM. Using a GLP-compliant platform, we now report the efficacy of MS-Hu6 in preventing and treating osteoporosis in mice and parameters of acute safety in monkeys. Biodistribution studies using Zr-labelled, biotinylated or unconjugated MS-Hu6 in mice and monkeys showed localization to bone and bone marrow. MS-Hu6 displayed a β phase t of 7.5 days (180 hours) in humanized Tg32 mice. We tested 217 variations of excipients using the protein thermal shift assay to generate a final formulation that rendered MS-Hu6 stable in solution upon freeze-thaw and at different temperatures, with minimal aggregation, and without self-, cross-, or hydrophobic interactions or appreciable binding to relevant human antigens. MS-Hu6 showed the same level of \u27humanness\u27 as human IgG1 and was non-immunogenic in ELISPOT assays for IL-2 and IFNg in human peripheral blood mononuclear cell cultures. We conclude that MS-Hu6 is efficacious, durable, and manufacturable, and is therefore poised for future human testing

Optimizing a therapeutic humanized follicle-stimulating hormone-blocking antibody formulation by protein thermal shift assay

Biopharmaceutical products are formulated using several Food and Drug Administration (FDA) approved excipients within the inactive ingredient limit to maintain their storage stability and shelf life. Here, we have screened and optimized different sets of excipient combinations to yield a thermally stable formulation for the humanized follicle-stimulating hormone (FSH)-blocking antibody, MS-Hu6. We used a protein thermal shift assay in which rising temperatures resulted in the maximal unfolding of the protein at the melting temperature (Tm ). To determine the buffer and pH for a stable solution, four different buffers with a pH range from 3 to 8 were screened. This resulted in maximal Tm s at pH 5.62 for Fab in phosphate buffer and at pH 6.85 for Fc in histidine buffer. Upon testing a range of salt concentrations, MS-Hu6 was found to be more stable at lower concentrations, likely due to reduced hydrophobic effects. Molecular dynamics simulations revealed a higher root-mean-square deviation with 1 mM than with 100 mM salt, indicating enhanced stability, as noted experimentally. Among the stabilizers tested, Tween 20 was found to yield the highest Tm and reversed the salt effect. Among several polyols/sugars, trehalose and sucrose were found to produce higher thermal stabilities. Finally, binding of recombinant human FSH to MS-Hu6 in a final formulation (20 mM phosphate buffer, 1 mM NaCl, 0.001% w/v Tween 20, and 260 mM trehalose) resulted in a thermal shift (increase in Tm ) for the Fab, but expectedly not in the Fc domain. Given that we used a low dose of MS-Hu6 (1 μM), the next challenge would be to determine whether 100-fold higher, industry-standard concentrations are equally stable

FSH blockade improves cognition in mice with Alzheimer\u27s disease

Alzheimer\u27s disease has a higher incidence in older women, with a spike in cognitive decline that tracks with visceral adiposity, dysregulated energy homeostasis and bone loss during the menopausal transition. Inhibiting the action of follicle-stimulating hormone (FSH) reduces body fat, enhances thermogenesis, increases bone mass and lowers serum cholesterol in mice. Here we show that FSH acts directly on hippocampal and cortical neurons to accelerate amyloid-β and Tau deposition and impair cognition in mice displaying features of Alzheimer\u27s disease. Blocking FSH action in these mice abrogates the Alzheimer\u27s disease-like phenotype by inhibiting the neuronal C/EBPβ-δ-secretase pathway. These data not only suggest a causal role for rising serum FSH levels in the exaggerated Alzheimer\u27s disease pathophysiology during menopause, but also reveal an opportunity for treating Alzheimer\u27s disease, obesity, osteoporosis and dyslipidaemia with a single FSH-blocking agent

First-in-class humanized FSH blocking antibody targets bone and fat.

Blocking the action of FSH genetically or pharmacologically in mice reduces body fat, lowers serum cholesterol, and increases bone mass, making an anti-FSH agent a potential therapeutic for three global epidemics: obesity, osteoporosis, and hypercholesterolemia. Here, we report the generation, structure, and function of a first-in-class, fully humanized, epitope-specific FSH blocking antibody with

Abstracts of National Conference on Biological, Biochemical, Biomedical, Bioenergy, and Environmental Biotechnology

This book contains the abstracts of the papers presented at the National Conference on Biological, Biochemical, Biomedical, Bioenergy, and Environmental Biotechnology (NCB4EBT-2021) Organized by the Department of Biotechnology, National Institute of Technology Warangal, India held on 29–30 January 2021. This conference is the first of its kind organized by NIT-W which covered an array of interesting topics in biotechnology. This makes it a bit special as it brings together researchers from different disciplines of biotechnology, which in turn will also open new research and cooperation fields for them. Conference Title: National Conference on Biological, Biochemical, Biomedical, Bioenergy, and Environmental BiotechnologyConference Acronym: NCB4EBT-2021Conference Date: 29–30 January 2021Conference Location: Online (Virtual Mode)Conference Organizer: Department of Biotechnology, National Institute of Technology Warangal, Indi

Suppression of essential pro-inflammatory signaling pathways by natural agents for the therapy of multiple myeloma

10.1007/s11101-013-9287-3Phytochemistry Reviews13179-106PRHE