Nishaan - The Target In Hindi Mp3 Free Download BEST

Particle-based delivery systems have been investigated for their potential to increase the efficacy of patient diagnoses and treatments. In many cases, these systems increase the bioavailability and/or decrease the toxicity of clinically relevant drugs. These developments have led to improvements in patient compliance, morbidity, mortality, and quality of life. To date, particle-based delivery systems have been evaluated in hundreds of clinical trials around the world. Unlike conventional delivery systems, particle-based delivery systems offer increased surface area, colloidal stability, and system tunability, all of which can be tailored to target the disease state of interest and specific patient population.

Although there are examples of successful particle-based drug products, there are numerous obstacles that consistently shunt the ability for these systems to be translated from benchside to bedside. Two consistent obstacles are drug toxicity and scale-up manufacturing. Drug toxicity is largely caused by inefficient targeting, inopportune routes of administration (i.e. oral delivery for a pulmonary disease), and unfavorable release mechanisms. Scale-up manufacturing is a continual industrial interest, given that particle-based drug products are increasing in popularity, however scale-up procedures are still in development and face their own challenges. A potential method to overcome the obstacles faced in drug delivery is the development of new polymers, either by synthesis of novel entities or derivatization of current ones. To ensure biocompatibility, the latter is a common practice. Biopolymers such as chitosan, hyaluronic acid, poly(lactic-co-glycolic acid) (PLGA), and naturally occurring polysaccharides undergo modifications to achieve desirable characteristics for drug delivery. Acetalated dextran (Ac-Dex) is a synthetic biopolymer derived from dextran, a naturally produced hydrophilic polysaccharide. Following a one-step reaction, the hydroxyl moieties of dextran are converted to acetal groups, transitioning the biopolymer from hydrophilic to lipophilic solubility. Hydroxyl moieties still present on the backbone can provide a handle for ligand attachment to actively target specific sites of the body. Additionally, controlling the reaction time and altering the molecular weight of the dextran backbone can alter the degradation kinetics, providing flexibility to achieve desirable release kinetics for a therapeutic of interest. Overall, Ac-Dex demonstrates cost-effective and efficient synthesis, easy tunability for targeting, and flexibility in controlling release kinetics, all of which propitiate its promise as a drug carrier.

Nishaan - The Target In Hindi Mp3 Free Download

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The purpose of this dissertation was to utilize the advantages of Ac-Dex to investigate its potential as a drug carrier to overcome challenges that exist in the field of drug delivery. Manuscript 1 focuses on decreasing drug toxicity using active targeting. Here, Ac-Dex nanoparticles (NP) were synthesized and coated with phosphatidylserine to instigate macrophage uptake for the potential to treat diseases that use these cells as reservoirs, such as tuberculosis and HIV. Manuscript 2 focuses on the synthesis of Ac-Dex microparticles (MP), followed by an exploration of their ability to modulate the release of water-soluble cargo. Ac-Dex MP were synthesized via spray drying and were loaded with a water-soluble dye. Following the synthesis, MP were evaluated for their characteristics and drug release behaviors in multiple pH environments. Manuscript 3 uses Ac-Dex as an economical model drug carrier and focused on studying the effects of tangential flow filtration (TFF) parameters (factors) on the characteristics of NP (responses) to explore its promise as a scale-up purification technique. The final manuscript focuses on the physical characterization and development of nanocomposite microparticle system for localized delivery of the small molecule Eact, a potential therapeutic for pulmonary arterial hypertension.

You need to use Visual Studio 2019 and its SQL Server Integration Services Projects extension to develop SSIS projects targeting 2016 version. It supports the following SSIS run-time versions: 2012, 2014, 2016, 2017, 2017, 2019, 2022.

Chlamydia trachomatis is involved in most sexually transmitted diseases. The species has emerged as a major public health threat due to its multidrug-resistant capabilities, and new therapeutic target inferences have become indispensable to combat its pathogenesis. However, no commercial vaccine is yet available to treat the C. trachomatis infection. In this study, we used the publicly available complete genome sequences of C. trachomatis and performed comparative proteomics and reverse vaccinology analyses to explore novel drug and vaccine targets against this devastating pathogen. We identified 713 core proteins from 71 C. trachomatis complete genome sequences and prioritized them based on their cellular essentiality, virulence, and available antibiotic resistance. The analyses led to the identification of 16 pathogen-specific proteins with no resolved 3D structures, though holding significant druggable potential. The sequences of the three shortlisted candidates' membrane proteins were used for designing vaccine constructs. The antigenicity, toxicity, and solubility profile-based lead epitopes were prioritized for multi-epitope-based vaccine constructs in combination with specific linkers, PADRE sequences, and molecular adjuvants for immunogenicity enhancement. The molecular-level interactions of the prioritized vaccine construct with human immune cells HLA and TLR4/MD were validated by molecular docking and molecular dynamic simulation analyses. Furthermore, the cloning and expression potential of the lead vaccine construct was predicted in the E. coli cloning vector system. Additional testing and experimental validation of these multi-epitope constructs appear promising against C. trachomatis-mediated infection.

Overactivation of the renin-angiotensin system (RAS) during obesity disrupts adipocyte metabolic homeostasis and induces endoplasmic reticulum (ER) stress and inflammation; however, underlying mechanisms are not well known. We propose that overexpression of angiotensinogen (Agt), the precursor protein of RAS in adipose tissue or treatment of adipocytes with Angiotensin II (Ang II), RAS bioactive hormone, alters specific microRNAs (miRNA), that target ER stress and inflammation leading to adipocyte dysfunction. Epididymal white adipose tissue (WAT) from B6 wild type (Wt) and transgenic male mice overexpressing Agt (Agt-Tg) in adipose tissue and adipocytes treated with Ang II were used. Small RNA sequencing and microarray in WAT identified differentially expressed miRNAs and genes, out of which miR-690 and mitogen-activated protein kinase kinase 3 (MAP2K3) were validated as significantly up- and down-regulated, respectively, in Agt-Tg, and in Ang II-treated adipocytes compared to respective controls. Additionally, the direct regulatory role of miR-690 on MAP2K3 was confirmed using mimic, inhibitors and dual-luciferase reporter assay. Downstream protein targets of MAP2K3 which include p38, NF-B, IL-6 and CHOP were all reduced. These results indicate a critical post-transcriptional role for miR-690 in inflammation and ER stress. In conclusion, miR-690 plays a protective function and could be a useful target to reduce obesity.

Neisseria gonorrhoeae is an emerging multidrug resistance pathogen that causes sexually transmitted infections in men and women. The N. gonorrhoeae has demonstrated an emerging antimicrobial resistance against reported antibiotics, hence fetching the attention of researchers to address this problem. The present in-silico study aimed to find putative novel drug and vaccine targets against N. gonorrhoeae infection by the application of bioinformatics approaches. Core genes set of 69 N. gonorrhoeae strains was acquired from complete genome sequences. The essential and non-homologous metabolic pathway proteins of N. gonorrhoeae were identified. Moreover, different bioinformatics databases were used for the downstream analysis. The DrugBank database scanning identified 12 novel drug targets in the prioritized list. They were preferred as drug targets against this bacterium. A viable vaccine is unavailable so far against N. gonorrhoeae infection. In the current study, two outer-membrane proteins were prioritized as vaccine candidates via reverse vaccinology approach. The top lead B and T-cells overlapped epitopes were utilized to generate a chimeric vaccine construct combined with immune-modulating adjuvants, linkers, and PADRE sequences. The top ranked prioritized vaccine construct (V7) showed stable molecular interaction with human immune cell receptors as inferred during the molecular docking and MD simulation analyses. Considerable response for immune cells was interpreted by in-silico immune studies. Additional tentative validation is required to ensure the effectiveness of the prioritized vaccine construct against N. gonorrhoeae infection. The identified proteins can be used for further rational drug and vaccine designing to develop potential therapeutic entities against the multi-drug resistant N. gonorrhoeae.

Citation: Qasim A, Jaan S, Wara TU, Shehroz M, Nishan U, Shams S, Shah M and Ojha SC (2023) Computer-aided genomic data analysis of drug-resistant Neisseria gonorrhoeae for the Identification of alternative therapeutic targets. Front. Cell. Infect. Microbiol. 13:1017315. doi: 10.3389/fcimb.2023.1017315

Nishan delivered his inaugural address as President and Vice-Chancellor at the University of Leicester in January 2020. During his address he announced the development of the Leicester Institute for Inclusion in Higher Education and pledged that the University would achieve a net zero carbon emission target by 2040. be457b7860