Regulation of Zfp36 by ISGF3 and MK2 restricts the expression of inflammatory cytokines during necroptosis stimulation.

Necrosome activation following TLR- or cytokine receptor-signaling results in cell death by necroptosis which is characterized by the rupture of cell membranes and the consequent release of intracellular contents to the extracellular milieu. While necroptosis exacerbates various inflammatory diseases, the mechanisms through which the inflammatory responses are regulated are not clear. We show that the necrosome activation of macrophages results in an upregulation of various pathways, including the mitogen-activated protein kinase (MAPK) cascade, which results in an elevation of the inflammatory response and consequent expression of several cytokines and chemokines.

Screening inhibitors against the Ef-Tu of Fusobacterium nucleatum: a docking, ADMET and PBPK assessment study.

The oral pathogen Fusobacterium nucleatum has recently been associated with an elevated risk of colorectal cancer (CRC), endometrial metastasis, chemoresistance, inflammation, metastasis, and DNA damage, along with several other diseases. This study aimed to explore the disruption of protein machinery of F. nucleatum via inhibition of elongation factor thermo unstable (Ef-Tu) protein, through natural products.

Chimeric vaccine design against the conserved TonB-dependent receptor-like β-barrel domain from the outer membrane tbpA and hpuB proteins of ATCC 23330.

is a Gram-negative bacterium that primarily causes pediatric infections such as septicemia, endocarditis, and osteoarticular infections. Its virulence is attributed to the outer membrane proteins having implications in bacterial adhesion, invasion, nutrition, and host tissue damage. TonB-dependent receptors (TBDRs) play an important role in nutrition and were previously implicated as vaccine targets in other bacteria.

Mining Autoimmune-Disorder-Linked Molecular-Mimicry Candidates in and Prospects of Mimic-Based Vaccine Design: An In Silico Approach.

Molecular mimicry, a phenomenon in which microbial or environmental antigens resemble host antigens, has been proposed as a potential trigger for autoimmune responses. In this study, we employed a bioinformatics approach to investigate the role of molecular mimicry in -caused infections and the induction of autoimmune disorders due to this phenomenon. Comparing proteomes of host and pathogen, we identified 23 proteins that exhibited significant sequence homology and were linked to autoimmune disorders.

Molecular Mimicry Mapping in : Cues for Autoimmune Disorders and Implications for Immune Defense Activation.

contributes to a range of infections, including meningitis, pneumonia, otitis media, and sepsis. Infections by this bacterium have been associated with the phenomenon of molecular mimicry, which, in turn, may contribute to the induction of autoimmunity. In this study, we utilized a bioinformatics approach to investigate the potential for to incite autoimmunity via molecular mimicry.

Molecular Role of Asn680Ser and Asp37Glu Missense Variants in Saudi Women with Female Infertility and Polycystic Ovarian Syndrome.

Female infertility (FI) is a global health issue. Polycystic ovary syndrome (PCOS) is a common cause of FI. The renalase gene () is associated with FI and other human diseases.

Review of the Immune Checkpoint Inhibitors in the Context of Cancer Treatment.

Checkpoint proteins are an integral part of the immune system and are used by the tumor cells to evade immune response, which helps them grow uncontrollably. By blocking these proteins, immune checkpoint inhibitors can restore the capability of the immune system to attack cancer cells and stop their growth. These findings are backed by adequate clinical trial data and presently, several FDA-approved immune checkpoint inhibitors exist in the market for treating various types of cancers, including melanoma, hepatocellular, endometrial, lung, kidney and others.

Therapeutic potential of bone marrow mesenchymal stem cells in cyclophosphamide-induced infertility.

Cancer is a deadly disease characterized by abnormal cell proliferation. Chemotherapy is one technique of cancer treatment. Cyclophosphamide (CYP) is the most powerful chemotherapy medication, yet it has serious adverse effects.

Targeting Kaposi's sarcoma associated herpesvirus encoded protease (ORF17) by a lysophosphatidic acid molecule for treating KSHV associated diseases.

Kaposi's sarcoma associated herpesvirus (KSHV) is causative agent of Kaposi's sarcoma, Multicentric Castleman Disease and Pleural effusion lymphoma. KSHV-encoded ORF17 encodes a protease which cleaves -Ala-Ala-, -Ala-Ser- or -Ala-Thr-bonds. The protease plays an important role in assembly and maturation of new infective virions.

Ameliorative Effect of Citrus Lemon Peel Extract and Resveratrol on Premature Ovarian Failure Rat Model: Role of iNOS/Caspase-3 Pathway.

Premature ovarian failure (POF) is described as a loss of oocytes and the absence of folliculogenesis and is considered an adverse effect of chemotherapeutic drugs, which leads to infertility. Subsequently, the existing inquiry was achieved by exploring the potential suspicious influences of lemon peel extract (LPE), and resveratrol (RES) on cyclophosphamide (CPA) induced-POF. The results showed that CPA-induced POF significantly decreased serum estradiol (E2) and progesterone levels, along with a considerable rise in serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels.

Molecular mechanism of for the treatment of asthma: Network pharmacology and molecular docking approach.

Asthma is a significant health-care burden that has great impact on the quality of life of patients and their families. The limited amount of previously reported data and complicated pathophysiology of asthma make it a difficult to treat and significant economic burden on public healthcare systems. is an herbaceous, monoecious, perennial plant of the Umbelliferae family.

Therapeutic Target Identification and Inhibitor Screening against Riboflavin Synthase of Colorectal Cancer Associated .

Colorectal cancer (CRC) ranks third among all cancers in terms of prevalence. There is growing evidence that gut microbiota has a role in the development of colorectal cancer. Fusobacterium nucleatum is overrepresented in the gastrointestinal tract and tumor microenvironment of patients with CRC.

Distribution of Harboring Hypervirulent in Clinical Specimens and Lytic Activity of Bacteriophage Against Isolates.

Background: The World Health Organization (WHO) has declared the multi-drug resistant (MDR) as one of the critical bacterial pathogens. The dearth of new antibiotics and inadequate therapeutic options necessitate finding alternative options. Bacteriophages are known as enemies of bacteria and are well-recognized to fight MDR pathogens.

Level of Knowledge and Awareness of Female Undergraduate Students and Determinants of Knowledge of Folic Acid and Supplementation.

Background and Objectives: Folic acid (FA) is a necessary ingredient for numerous bodily activities including pregnancy. Because of this, women should have knowledge and awareness of the health benefits of FA supplementation. Thus, we aimed to investigate the level of knowledge on the importance of FA and determine associated factors for knowledge among female college students at King Saud University in Riyadh, Saudi Arabia.

In-Silico Screening and Molecular Dynamics Simulation of Drug Bank Experimental Compounds against SARS-CoV-2.

For the last few years, the world has been going through a difficult time, and the reason behind this is severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), one of the significant members of the Coronaviridae family. The major research groups have shifted their focus towards finding a vaccine and drugs against SARS-CoV-2 to reduce the infection rate and save the life of human beings. Even the WHO has permitted using certain vaccines for an emergency attempt to cut the infection curve down.

Hemi-Babim and Fenoterol as Potential Inhibitors of MPro and Papain-like Protease against SARS-CoV-2: An In-Silico Study.

The coronaviruses belong to the Coronaviridae family, and one such member, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is causing significant destruction around the world in the form of a global pandemic. Although vaccines have been developed, their effectiveness and level of protection is still a major concern, even after emergency approval from the World Health Organisation (WHO). At the community level, no natural medicine is currently available as a cure.

Assessment of Using the Syndromic Approach in Managing Patients With Sexually Transmitted Diseases Among the National Guard Primary Health Care Physicians, Jeddah City, Saudi Arabia.

Background Sexually transmitted infections (STIs) include a group of clinical syndromes that can be transmitted mainly through sexual activity. Using STIs' syndromic approach for diagnosis and management is widely recommended to control and reduce the burden of these transmissible diseases. Objective The objective of this article is to assess the knowledge and practice of physicians concerning syndromic management of STIs in National Guard Primary Health Care (PHC) centers in Jeddah city, Saudi Arabia.

Isolated Perianal Endometrioma: A Case Report and Literature Review.

BACKGROUND Endometriosis, a common condition among women of reproductive age and infertile women, occurs when the endometrium extends outside the uterus. When this endometrial tissue grows and sheds, symptoms will develop. The presentation varies depending on the site involved; however, cyclical pain is among its most common symptoms, along with bleeding and cramping.

Impact of COVID-19 on Saudi Children: Special Focus on Behavioral, Social, and Emotional Aspects, 2020-2021.

Background The coronavirus disease 2019 (COVID-19) pandemic has negatively affected many aspects of daily life. In Saudi Arabia, many studies, using a range of assessment approaches, have examined how the pandemic has affected the mental health of both the general public and healthcare workers. However, to develop effective public-health initiatives for such crisis events, it would also be relevant to determine the pandemic's impact on the behavioral, emotional, and social lives of Saudi children.

Tristetraprolin regulates necroptosis during tonic Toll-like receptor 4 (TLR4) signaling in murine macrophages.

The necrosome is a protein complex required for signaling in cells that results in necroptosis, which is also dependent on tumor necrosis factor receptor (TNF-R) signaling. TNFα promotes necroptosis, and its expression is facilitated by mitogen-activated protein (MAP) kinase-activated protein kinase 2 (MK2) but is inhibited by the RNA-binding protein tristetraprolin (TTP, encoded by the gene). We have stimulated murine macrophages from WT, , , , , and mice with graded doses of lipopolysaccharide (LPS) and various inhibitors to evaluate the role of various genes in Toll-like receptor 4 (TLR4)-induced necroptosis.

Differentiated macrophages acquire a pro-inflammatory and cell death-resistant phenotype due to increasing XIAP and p38-mediated inhibition of RipK1.

Monocytes differentiate into macrophages, which deactivate invading pathogens. Macrophages can be resistant to cell death mechanisms in some situations, and the mechanisms involved are not clear. Here, using mouse immune cells, we investigated whether the differentiation of macrophages affects their susceptibility to cell death by the ripoptosome/necrosome pathways.