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Xylan extracted from neem sawdust gave 22.5%, (w/w) yield. The extracted xylan was composed of xylose and glucuronic acid at a molar ratio of 8:1 and with a molecular mass, ~66 kDa. FTIR and NMR analyses indicated a backbone of xylan substituted with 4- O -methyl glucuronic acid at the O-2 position. FESEM analysis showed a highly porous and granular surface structure of xylan. A thermogravimetric study of xylan showed thermal denaturation at 271 °C. The hydrolysis of xylan by recombinant endo-β-1,4-xylanase produced a mixture of xylooligosaccharides ranging from degree of polymerization 2–7. Xylooligosaccharides inhibited cell growth of human colorectal cancer (HT-29) cells but did not affect the mouse fibroblast cells confirming its biocompatibility. Western blotting, DNA laddering and flow cytometric analysis displayed inhibition of HT-29 cells by xylooligosaccharides. FLICA staining and mitochondrial membrane potential analyses confirmed the activation of the intrinsic pathway of apoptosis. The study amply indicated that the xylooligosaccharides produced from neem xylan could be potentially used as an antiproliferative agent. [ABSTRACT FROM AUTHOR]

Rabies virus (RABV) is the causative agent of a fatal nervous system ailment. The disease is zoonotic and prevalent in many developing countries. The glycoprotein (G) of RABV is the major antigenic determinant of the virus and plays a pivotal role in its neurovirulence. Various aspects of ‘G’ protein biology have been explored, but the factors affecting the nucleotide choice and synonymous codon usage have never been reported. In the present study, we have analyzed the relative synonymous codon usage and effective number of codons (Nc) using 132 ‘G’ protein genes of RABV. Corresponding analysis was used to calculate major trends in codon usage. The correlation between base composition and codon usage as well as the plot between Nc and GC3 suggest that mutational pressure is the major factor that influences the codon usage in the G gene of RABV. In addition, factors like aromaticity, aliphatic index and hydropathy have shown slight correlation suggesting that natural selection also contributes to the codon usage variations of the ‘G’ gene. In conclusion, codon usage bias in ‘G’ gene of RABV is mainly by mutational pressure and natural selection. [ABSTRACT FROM AUTHOR]

The abnormal assembly of tau into neurofibrillary tangles has been associated with over 30 debilitating disorders known as tauopathies. Tauopathies affect millions of people worldwide, yet no clinically approved solution for tau aggregation is currently available. We employed a structure-based design approach to make a series of short peptide-based perturbants (Trojans), that can interact with the core hydrophobic fragment of tau protein. Through a combination of various biophysical methods, serum stability, toxicity, and blood-brain barrier translocation assays, we have assessed the efficacy of these designed peptides to intervene the aggregation of tau protein fragment. Our observations suggest that Trojan peptides could modulate the aggregation of the Ac-VQIVYK-NH 2 peptide by either accelerating or arresting its self-assembly and reduce the neurotoxicity of the fibrils formed. The designed perturbant peptides showed three essential pre-requisites such as negligible cytotoxicity, high proteolytic stability in serum, and an ability to cross human blood-brain barrier (BBB). Furthermore, the Trojans could disassemble the pre-formed fibrillar assemblies. These designed Trojan peptides can serve as a potential therapeutic option for tauopathies, modulating post as well as pre-aggregation leading to the diseases condition. Tauopathies are a group of over 20 progressive neurodegenerative disorders that affect millions of people worldwide. The available therapies of tau-linked neurodegenerative syndromes are limited and mostly symptomatic and therefore there is an urgent need for a cost-effective treatment option. We are presenting a series of structure-based, de novo designed, short peptides that can potentially modulate tau protein aggregation. Unlabelled Image • 'Tauopathies' is a collective term over 30 neurodegenerative characterized by the abnormal tau aggregation in the brain. • Modulatory approaches targeting pathological aggregation of tau in Alzheimer's disease have shown a lot of promise. • Short peptides as modulators of toxic tau aggregation, offer several advantages over other small molecule-based strategies. • Structure-based designed 'trojan peptides' could breach the tight junctions of the core hydrophobic peptide segment of tau. [ABSTRACT FROM AUTHOR]

Newcastle disease (ND) is prevalent among the domesticated and the wild birds and is caused by the avian paramyxovirus serotype-I (APMV-I). It is commonly known to affect chicken, pheasant, ostrich, pigeon and waterfowl. Depending on the virulence, the velogenic NDV strains cause severe respiratory and nervous disorders with a high mortality rate. The live and killed vaccines are available for the prevention of infection in the market, but the drug for the treatment is not available. Nitazoxanide (NTZ), a member of thiazolides, is an antiparasitic drug. In the present study, the effect of NTZ on the NDV replication was explored. The experiments were conducted in chicken fibroblast cells (DF-1), PBMC, embryonated chicken eggs, and two-week old chickens. The inhibition of the NDV was observed upon post-treatment of NTZ at a concentration of ~12.5 μM. Cytokine profiling of the DF-1, PBMC, and chicken embryonic tissue treated with NTZ revealed significant upregulation in all the cytokines studied except for IL-1β in DF-1 cells. It is plausible that NTZ is involved in causing immune-modulatory effects in poultry. NTZ treatment in two weeks old chicken showed significant reduction in NDV replication in trachea, and lungs, respectively, at 72 h post-infection. Encouraging results from the present study warrants repurposing NTZ as a drug for the treatment of viral infection in poultry. It will also pave the way towards understanding of similar effect against other animal pathogens. [ABSTRACT FROM AUTHOR]

Background: Tumor-targeted therapy causes impressive tumor regression, but the emergence of resistance limits long-term survival benefits in patients. Little information is available on the role of the myeloid cell network, especially dendritic cells (DC) during tumor-targeted therapy., Methods: Here, we investigated therapy-mediated immunological alterations in the tumor microenvironment (TME) and tumor-draining lymph nodes (LN) in the D4M.3A preclinical melanoma mouse model (harboring the V-Raf murine sarcoma viral oncogene homolog B (BRAF) V600E mutation) by using high-dimensional multicolor flow cytometry in combination with multiplex immunohistochemistry. This was complemented with RNA sequencing and cytokine quantification to characterize the immune status of the tumors. The importance of T cells during tumor-targeted therapy was investigated by depleting CD4 + or CD8 + T cells in tumor-bearing mice. Tumor antigen-specific T-cell responses were characterized by performing in vivo T-cell proliferation assays and the contribution of conventional type 1 DC (cDC1) to T-cell immunity during tumor-targeted therapy was assessed using Batf3 -/- mice lacking cDC1., Results: Our findings reveal that BRAF-inhibitor therapy increased tumor immunogenicity, reflected by an upregulation of genes associated with immune activation. The T cell-inflamed TME contained higher numbers of activated cDC1 and cDC2 but also inflammatory CCR2-expressing monocytes. At the same time, tumor-targeted therapy enhanced the frequency of migratory, activated DC subsets in tumor-draining LN. Even more, we identified a cDC2 population expressing the Fc gamma receptor I (FcγRI)/CD64 in tumors and LN that displayed high levels of CD40 and CCR7 indicating involvement in T cell-mediated tumor immunity. The importance of cDC2 is underlined by just a partial loss of therapy response in a cDC1-deficient mouse model. Both CD4 + and CD8 + T cells were essential for therapy response as their respective depletion impaired therapy success. On resistance development, the tumors reverted to an immunologically inert state with a loss of DC and inflammatory monocytes together with the accumulation of regulatory T cells. Moreover, tumor antigen-specific CD8 + T cells were compromised in proliferation and interferon-γ-production., Conclusion: Our results give novel insights into the remodeling of the myeloid landscape by tumor-targeted therapy. We demonstrate that the transient immunogenic tumor milieu contains more activated DC. This knowledge has important implications for the development of future combinatorial therapies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Vaccines are the most effective and economic way of combating poultry viruses. However, the use of traditional live-attenuated poultry vaccines has problems such as antigenic differences with the currently circulating strains of viruses and the risk of reversion to virulence. In veterinary medicine, reverse genetics is applied to solve these problems by developing genotype-matched vaccines, better attenuated and effective live vaccines, broad-spectrum vaccine vectors, bivalent vaccines, and genetically tagged recombinant vaccines that facilitate the serological differentiation of vaccinated animals from infected animals. In this chapter, we discuss reverse genetics as a tool for the development of recombinant vaccines against economically devastating poultry viruses., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Synthetic anion transporters have been recognized as one of the potential therapeutic agents for the treatment of diseases including cystic fibrosis, myotonia, and epilepsy that originate due to the malfunctioning of natural Cl - ion transport systems. Recent studies showed that the synthetic Cl - ion transporters can also disrupt cellular ion-homeostasis and induce apoptosis in cancer cell lines, leading to a revived attention for synthetic Cl - ion transporters. Herein, we report the development of conformationally controlled 1,2-diphenylethylenediamine-based bis(thiourea) derivatives as a new class of selective Cl - ion carrier. The strong Cl - ion binding properties ( K d = 3.87-6.66 mM) of the bis(thiourea) derivatives of diamine-based compounds correlate well with their transmembrane anion transport activities (EC 50 = 2.09-4.15 nM). The transport of Cl - ions via Cl - /NO 3 - antiport mechanism was confirmed for the most active molecule. Perturbation of Cl - ion homeostasis by this anion carrier induces cell death by promoting the caspase-mediated intrinsic pathway of apoptosis.

The complete genome sequence of a Newcastle disease virus (NDV) strain NDV/Chicken/Nagpur/01/12 was isolated from vaccinated chicken farms in India during outbreaks in 2012. The genome is 15,192 nucleotides in length and is classified as genotype VII in class II., (Copyright © 2015 Gogoi et al.)

The complete genome sequence was determined for a Newcastle disease virus strain from vaccinated chicken farms in India during outbreaks in 2010. The genome is 15,192 nucleotides (nt) in length and is classified as genotype VII in class II. Compared to the available vaccine strains, the Indian strain contains a previously described 6-nt insertion in the untranslated region of the nucleoprotein gene.