miR-199a-3p suppresses neuroinflammation by directly targeting MyD88 in a mouse model of bone cancer pain.

AIMS: Pain is a profoundly debilitating symptom in cancer patients, leading to disability, immobility, and a marked decline in their quality of life. This study aimed to investigate the potential roles of miR-199a-3p in a murine model of bone cancer pain induced by tumor cell implantation in the medullary cavity of the femur. MATERIALS AND METHODS: We assessed pain-related behaviors, including the paw withdrawal mechanical threshold (PWMT) and the number of spontaneous flinches (NSF). To investigate miRNA expression and its targets in astrocytes, we employed a combination of RNA-seq analysis, qRT-PCR, Western blotting, EdU, TUNEL, ChIP, ELISA, and luciferase reporter assays in mice (C3H/HeJ) with bone cancer pain and control groups. KEY FINDINGS: On days 10, 14, 21, and 28 post-surgery, we observed significant differences in PWTL, PWMT, and NSF when compared to the sham group (P < 0.001). qRT-PCR assays and miRNA sequencing results confirmed reduced miR-199a-3p expression in astrocytes of mice with bone cancer pain. Gain- and loss-of-function experiments demonstrated that miR-199a-3p suppressed astrocyte activation and the expression of inflammatory cytokines. In vitro investigations revealed that miR-199a-3p mimics reduced the levels of inflammatory factors in astrocytes and MyD88/NF-κB proteins. Furthermore, treatment with a miR-199a-3p agonist resulted in reduced expression of MyD88, TAK1, p-p65, and inflammatory mediators, along with decreased astrocyte activation in the spinal cord. SIGNIFICANCE: Collectively, these findings demonstrate that upregulation of miR-199a-3p may offer a therapeutic avenue for mitigating bone cancer pain in mice by suppressing neuroinflammation and inhibiting the MyD88/NF-κB signaling pathway.

Combining molecular modelling and experimental approaches to gain mechanistic insights into the LuxP drug target in Streptococcus pyogens.

Autoinducer-2 can mediate inter- and intra-species communication signal between bacteria and these signals from AI-2 is noted from limited species of bacteria. In humans, S. pyogenes is a pathogen that causes a wide range of illnesses and can survive in the host system and transmit infection. The process by which S. pyogenes acquires the competence to live and disseminate infection remains unknown. We hypothesized that AI-2 and their receptors would play a significant role during infection, and for that present investigation provides the experimental and molecular insights. In the absence of details about the receptor LuxP and LuxQ, the screening approach provides supporting insights. The evolutionary relationship and similarities of the PBP domain (Spy 1535) and the signal transmission PDZ domain (Spy 1536) were studied in relation to their counterparts in other bacteria. Molecular docking and modeling confirmed the domain-enhanced specificity for AI-2 binding. In vitro studies showed that AI-2, which is present in the cell-free supernatant of S. pyogenes, regulates luminescence in P. luminous and biofilm development in E. coli using the LuxS reporter genes. Examination of S. pyogenes gene expression revealed modulation of virulence genes when the pathogen was exposed to V. harveyi HSL and AI-2. Therefore, S. pyogenes pathogenicity is sequentially regulated by AI-2 it acquires from other commensal bacteria. Overall, this study lays the groundwork for understanding the signalling mechanism from AI-2, which are critical to the pathogenic mechanism of S. pyogenes.Communicated by Ramaswamy H. Sarma.

Biopolymer Chitosan Surface Engineering with Magnesium Oxide-Pluronic-F127-Escin Nanoparticles on Human Breast Carcinoma Cell Line and Microbial Strains.

Nanotechnology has been recognized as a highly interdisciplinary field of the twenty-first century, with diverse applications in biotechnology, healthcare, and material science. One of the most commonly employed non-toxic nanoparticles, magnesium oxide nanoparticles (MgO NPs), is simple, inexpensive, biocompatible, and biodegradable. Several researchers are interested in the biosynthesis process of MgO NPs through chemical and physical approaches. This is because of their simplicity, affordability, and environmental safety. In the current study, green MgO-Chitosan-Pluronic F127-Escin (MCsPFE) NPs have been synthesized and characterized via various techniques like UV-visible, Fourier-transform infrared spectroscopy, Energy dispersive X-ray composition analysis, Transmission electron microscopy, field emission scanning electron microscopy, X-ray Diffraction, Photoluminescence, and Dynamic light scattering analyses. The average crystallite size of MCsPFE NPs was 46 nm, and a face-centered cubic crystalline structure was observed. Further, the antimicrobial effectiveness of NPs against diverse pathogens has been assessed. The cytotoxic potential of the nanoparticles against MDA-MB-231 cell lines was evaluated using the MTT test, dual AO/EB, JC-1, DCFH-DA, and DAPI staining procedures. High antimicrobial efficacy of MCsPFE NPs against Gram-positive and Gram-negative bacterial strains as well as Candida albicans was observed. The findings concluded that the NPs augmented the ROS levels in the cells and altered the Δψm, leading to the initiation of the intrinsic apoptotic cell death pathway. Thus, green MCsPFE NPs possess immense potential to be employed as an effective antimicrobial and anticancer treatment option.

Husk-like Zinc Oxide Nanoparticles Induce Apoptosis through ROS Generation in Epidermoid Carcinoma Cells: Effect of Incubation Period on Sol-Gel Synthesis and Anti-Cancerous Properties.

This study effectively reports the influence of experimental incubation period on the sol-gel production of husk-like zinc oxide nanoparticles (ZNPs) and their anti-cancerous abilities. The surface morphology of ZNPs was studied with the help of SEM. With the use of TEM, the diameter range of the ZNPs was estimated to be ~86 and ~231 nm for ZNPA and ZNPB, prepared by incubating zinc oxide for 2 and 10 weeks, respectively. The X-ray diffraction (XRD) investigation showed that ZNPs had a pure wurtzite crystal structure. On prolonging the experimental incubation, a relative drop in aspect ratio was observed, displaying a distinct blue-shift in the UV-visible spectrum. Furthermore, RBC lysis assay results concluded that ZNPA and ZNPB both demonstrated innoxious nature. As indicated by MTT assay, reactive oxygen species (ROS) release, and chromatin condensation investigations against the human epidermoid carcinoma (HEC) A431 cells, ZNPB demonstrated viable relevance to chemotherapy. Compared to ZNPB, ZNPA had a slightly lower IC50 against A431 cells due to its small size. This study conclusively describes a simple, affordable method to produce ZNP nano-formulations that display significant cytotoxicity against the skin cancer cell line A431, suggesting that ZNPs may be useful in the treatment of cancer.

Intrinsically disordered proteins in viral pathogenesis and infections.

Disordered proteins serve a crucial part in many biological processes that go beyond the capabilities of ordered proteins. A large number of virus-encoded proteins have extremely condensed proteomes and genomes, which results in highly disordered proteins. The presence of these IDPs allows them to rapidly adapt to changes in their biological environment and play a significant role in viral replication and down-regulation of host defense mechanisms. Since viruses undergo rapid evolution and have a high rate of mutation and accumulation in their proteome, IDPs' insights into viruses are critical for understanding how viruses hijack cells and cause disease. There are many conformational changes that IDPs can adopt in order to interact with different protein partners and thus stabilize the particular fold and withstand high mutation rates. This chapter explains the molecular mechanism behind viral IDPs, as well as the significance of recent research in the field of IDPs, with the goal of gaining a deeper comprehension of the essential roles and functions played by viral proteins.

Cyanobacteria-Mediated Immune Responses in Pepper Plants against Fusarium Wilt.

Research in plant pathology has increasingly focused on developing environmentally friendly, effective strategies for controlling plant diseases. Cyanobacteria, including Desmonostoc muscorum, Anabaena oryzae, and Arthrospiraplatensis, were applied to Capsicum annuum L. to induce immunity against Fusarium wilt. Soil irrigation and foliar shoots (FS) application were used in this investigation. The disease symptoms, disease index, osmotic contents, total phenol, Malondialdehyde (MDA), hydrogen peroxide (H2O2), antioxidant enzymes (activity and isozymes), endogenous hormone content, and response to stimulation of defense resistance in infected plants were assessed. Results demonstrated that using all cyanobacterial aqueous extracts significantly reduced the risk of infection with Fusarium oxysporum. One of the most effective ways to combat the disease was through foliar spraying with Arthrospira platensis, Desmonostoc muscorum, and Anabaena oryzae (which provided 95, 90, and 69% protection percent, respectively). All metabolic resistance indices increased significantly following the application of the cyanobacterial aqueous extracts. Growth, metabolic characteristics, and phenols increased due to the application of cyanobacteria. Polyphenol oxidase (PPO) and peroxidase (POD) expressions improved in response to cyanobacteria application. Furthermore, treatment by cyanobacteria enhanced salicylic acid (SA) and Indole-3-Acetic Acid (IAA) in the infected plants while decreasing Abscisic acid (ABA). The infected pepper plant recovered from Fusarium wilt because cyanobacterial extract contained many biologically active compounds. The application of cyanobacteria through foliar spraying seems to be an effective approach to relieve the toxic influences of F. oxysporum on infected pepper plants as green and alternative therapeutic nutrients of chemical fungicides.