The short non-coding microRNAs (miRNAs) have emerged as reliable modulators of various pathological conditions including autoimmune diseases in mammals. The current study, aims to identify new potential differential expressed miRNAs and their downstream mRNA targets of the autoimmune disease, Multiple sclerosis (MS). The study identifies a new set of miRNA(s) that are probably implicated in MS using computational tools. The study further carried-out different in vivo and in vitro experiments to check these identified miRNAs could be role in as therapeutic and prognostic applications. Preliminary insilico screening revealed that miR-659-3p, miR659-5p, miR-684, miR-3607-3p, miR-3607-5p, miR-3682-3p, miR-3682-5p miR-4647, miR-7188-3p, miR-7188- 5p and miR-7235 are specifically elevated in the secondary lymphoid cells of EAE mice. In addition, expression of the downstream target mRNA of these miRNAs such as FXBO33, SGMS-1, ZDHHC-9, GABRA-3, NRXN-2 were reciprocal to miRNA expression in lymphoid cells. These confirmed by applying the mimic and silencing miRNA models, suggesting new inflammatory target genes of these promising miRNA markers. The in vivo adoptive transfer model revealed that the suppression of miRNA-7188-5p and miR-7235 changed the pattern of astrocytes and CNS pathophysiology. The current study opens a new miRNA and their mRNA targets in MS disease. The absence of miRNA-7188-5p and miR-7235 enhanced the disease alleviation, confirms the regulatory effect of these targets. These optimized results highlights new set of miRNA’s with therapeutic potential in experimental MS. Further studies are required to confirm these miRNA as therapeutic biomarker.

Rheumatoid arthritis (RA) is a chronic autoimmune, multifactorial, inflammatory disorder characterized by hyperplasia and infiltration of inflammatory cells at the synovial lining leading to destruction of cartilage and bone tissues. Pinocembrin (PCB) is a natural flavonoid extracted as a pure molecule from honey, propolis, and some plants. In this study, we evaluated the antiarthritic effect of PCB in adjuvant induced arthritis (AIA) mice. Treating the AIA mouse model with PCB reduced the arthritis symptoms/score, including edema size, extent of hind paw redness, abnormal movement, and holding inability. At the pathological level, PCB significantly decreased the joint erosion and percentages of infiltrated inflammatory cells. Biochemically, PCB interacts with the transcription factor, SRY-related HMG-box 4 (Sox4), and then modulates its dysregulated expression and the expression of Sox4/Stat3 signaling molecules in AIA mice. These molecules include tumor necrosis factor-α, nuclear transcription factor kappaB, and cyclooxygenase-2, besides the microRNAs; miR-132, miR-202-5p, and miR-7235, which are dysregulated in adjuvant-induced arthritis model relative to the control mice. The possible PCB interaction with Sox4 transcriptional protein was confirmed through molecular docking where three hydrogen bonds were formed at ARG and LYS residues at a stable binding energy of -4.72. Taken together, our data demonstrate that PCB could serve as a therapeutic drug in treatment of RA.

Atherosclerosis is a persistent inflammatory disorder specified by the dysfunction of the arteries, the world's leading cause of cardiovascular diseases. We sought to determine the effectiveness of KRL in B[a]P-induced oxidative stress and programmed cell death in endothelial cells. Western blotting, real-time PCR, DCFH2-DA, and TUNEL staining were performed to detect pPI3K, pAKT, Nrf2, HO-1, NQO-1, Bcl2, Bax, and caspase-3 on the HUVECs. Through the pretreatment of KRL, a drastic enhancement was observed in the cell viability of HUVECs, whereas DNA damage and generation of reactive oxygen species induced by B[a]P was suppressed. KRL's potential use as an antioxidant was observed to have a direct correlation with an antioxidant gene's augmented expression and the nuclear translocation activation of Nrf2, even during the event when B[a]P was found to be absent. In addition, this study proved that the signaling cascades of PI3K/AKT mediated Nrf2 translocation. Activation of suppressed nuclear Nrf2 and reduced antioxidant genes across cells interacting with an LY294002 confirmed this phenomenon. In addition, knockdown of Nrf2 by Nrf2-siRNA transfection abolished the protective effects of KRL on HUVECs cells against oxidative damage. Finally, the expression of apoptotic proteins also supported the hypothesis that KRL may inhibit endothelial dysfunction. This study showed that KRL potentially prevents B[a]P-induced redox imbalance in the vascular endothelium by inducing the Nrf2 signaling via the PI3K/AKT pathway.

This paper fosters both uniform spaces and way-below relations with an innovative analysis of their mutual relationships. A new concept of uniform spaces based on a way below relation (LB-fuzzifying uniform space, or LBFU space, for short) will be introduced and investigated. With this aim, first, some fundamental concepts in L-fuzzifying topological spaces will be studied. Then, we shall explore some L-fuzzifying topological spaces induced by an LBFU space. Furthermore, new concepts of the interior, closure, bases, and subbases relative to an LBFU topology will be established. Finally, the continuity of functions between LBFU spaces will be introduced and investigated.

© The Author(s) under exclusive licence to Sociedade Brasileira de Matemática Aplicada e Computacional 2022

In this paper, some lower separation axioms in interval-valued intuitionistic fuzzy topological spaces are proposed. Furthermore, we pay some attention to determining the corresponding variations of them in intuitionistic fuzzy topological spaces. The four different types of the concepts of R◦-ness, T◦-ness, and T1-ness separation axioms are developed and the corresponding R1-ness and T2-ness are defined. Also, some conclusions by establishing some results are drawn and several examples for illustration are provided.

Pollution with heavy metals is a common problem worldwide that affects the growth of important crops and human health due to the consumption of contaminated crops. In the recent study, a set of 103 diverse spring wheat genotypes were evaluated for their tolerance to two important metals (lead and tin). The effect of these metals on kernel traits was measured to select tolerant and high-yielding genotypes. A great reduction in kernel length, kernel diameter, kernel width, and thousand kernel weight were found due to the effect of both metals. However, a highly significant correlation between the studied kernel traits was found suggesting their efficiency to indirectly select high yielding genotypes under heavy metals stress. In addition, the effect of the studied heavy metals on the physiological process was investigated and different responses to each metal were found suggesting that there are two different tolerant 

Heavy metal pollution is considered to be a major constraint of the ecosystem in current times. Heavy metals present in the earth’s crust naturally. The intoxication emerges when they are accumulated above the threshold into the environment via natural and/or anthropogenic activities, modern industrialization and some agricultural practices. Large areas of land have been polluted with heavy metals owing to the extensive application of pesticides, fertilizers, municipal and compost wastes, and also due to heavy metal release from smelting industries and metalliferous mines. Heavy metals potentially affect plant growth, metabolism and ionic status. Modification of the oxidative status of the cells is the predominant effect of heavy metals via excessive reactive oxygen species (ROS). Moreover, once inside the cells, heavy metals deregulate the defense components and homeostasis between the production of ROS and

The purpose of this paper is to introduce a new extension of the generalized admissible S-algorithm
for approximating common fixed point of three multivalued mappings satisfying two general
classes of contraction conditions in a uniformly convex Banach space endowed with a graph. As
an application of our result we establish the solution of image recovery problem in Hilbert space
setting.