Substrate-Induced Structural Dynamics and Evolutionary Linkage of Siderophore-Iron ABC Transporters of .

: ATP-binding cassette (ABC) transporters are prominent drug targets due to their highly efficient trafficking capabilities and their significant physiological and clinical roles. Gaining insight into their biophysical and biomechanistic properties is crucial to maximize their pharmacological potential. : In this study, we present the biochemical and biophysical characterization, and phylogenetic analysis of the domains of () ABC transporters: the exporter Rv1348 (IrtA) and the importer system Rv1349-Rv2895c (IrtB-Rv2895c), both involved in siderophore-mediated iron uptake.

MicroRNA-155, a double-blade sword regulator of innate tuberculosis immunity.

Tuberculosis (TB) is a chronic, life-threatening disease caused by unusual facultative intracellular bacteria, Mycobacterium tuberculosis. This bacterium has unique resistance to many antimicrobial agents and has become a major global health concern due to emerging multidrug-resistant strains. Additionally, it has developed multiple schemes to exploit host immune signaling and establish long-term survival within host tissues.

Identification and Functional Characterization of Mutation in in Families with Congenital Cataract.

Congenital cataract (CC) causes a third of the cases of treatable childhood blindness worldwide. CC is a disorder of the crystalline lens which is established as clinically divergent and has complex heterogeneity. This study aimed to determine the genetic basis of CC.

Biological Role of Zinc in Liver Cirrhosis: An Updated Review.

Liver cirrhosis is a complication usually due to the consequence of persistent chronic liver disease. It is associated with different mechanisms, including hypoalbuminemia, impaired amino acid turnover, and micronutrient deficiencies. Consequently, cirrhotic patients can develop progressive complications like ascites, hepatic encephalopathy, and hepatocellular carcinoma.

Adenosine A receptor as a potential target for improving cancer immunotherapy.

The adenosine nucleoside performs a wide range of actions on various human tissues by activating four cell surface receptors. Adenosine A receptors (ARs) are widely expressed in the striatum, olfactory bulb, platelets, leukocytes, spleen, and thymus. They promote vasodilatation, platelet antiaggregatory effect, protection from ischemic damage, and regulation of sensorimotor neurons in basal ganglia.

Determination of serum tumor necrosis factor-alpha (TNF-α) levels in metabolic syndrome patients from Saudi population.

Objectives: To detect the relationship between serum tumor necrosis factor-alpha (TNF-α) and metabolic syndrome (MetS) components in patients of the Saudi population.

Methods: This cross-sectional study was carried out at Jouf University Saudi Arabia from September 2019 to August 2020 and comprised of 183 individuals (91 cases and 92 controls). The blood samples were drawn from the patients visiting two tertiary care settings of Al Jouf province.

Molecular Epidemiology of Extensively-Drug Resistant Sequence Type 2 Co-Harboring and From Clinical Origin.

Background: The therapeutic management of carbapenem-resistant (CR-AB) represents a serious challenge to the public health sector because these pathogens are resistant to a wide range of antibiotics, resulting in limited treatment options. The present study was planned to investigate the clonal spread of CR-AB in a clinical setting.

Methodology: A total of 174 clinical isolates were collected from a tertiary care hospitals in Lahore, Pakistan.

Heavy Metal Tolerance Trend in Extended-Spectrum β-Lactamase Encoding Strains Recovered from Food Samples.

This study evaluates bacteriological profiles in ready-to-eat (RTE) foods and assesses antibiotic resistance, extended-spectrum β-lactamase (ESBL) production by gram-negative bacteria, and heavy metal tolerance. In total, 436 retail food samples were collected and cultured. The isolates were screened for ESBL production and molecular detection of ESBL-encoding genes.

Targeting Adenosine Receptors in Neurological Diseases.

Adenosine plays a significant role in neurotransmission process by controlling the blood pressure, while adenosine triphosphate (ATP) acts as a neuromodulator and neurotransmitter and by activation of P2 receptors, regulates the contractility of the heart. Adenosine signaling is essential in the process of regeneration by regulating proliferation, differentiation, and apoptosis of stem cells. In this review, we have selected neurological disorders (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and epilepsy) with clinical trials using antagonists and epigenetic tools targeting adenosine receptor as a therapeutic approach in the treatment of these disorders.

Insight into the emerging role of SARS-CoV-2 nonstructural and accessory proteins in modulation of multiple mechanisms of host innate defense.

Coronavirus disease-19 (COVID-19) is an extremely infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has become a major global health concern. The induction of a coordinated immune response is crucial to the elimination of any pathogenic infection. However, SARS-CoV-2 can modulate the host immune system to favor viral adaptation and persistence within the host.

Therapeutic Impact of ODN2088 to Block TLR9 Activity in Induced Liver Fibrosis Mice.

Background And Objective: Liver fibrosis is the result of an excessive accumulation of extracellular matrix that develops when inflammation and chronic injury form scar tissue in the liver. Toll-like receptor 9 (TLR9) plays a central role in the innate immune response by recognition of pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs). This study aimed to show the therapeutic effects of TLR9 antagonist oligonucleotide (ODN) 2088 on liver fibrogenesis.

Impact of Prostate Specific Antigen and Testosterone Hormone Levels in Patients of Benign Prostatic Hyperplasia in Khartoum State-Sudan.

Background And Objective: Lower Urinary Tract Symptoms (LUTS) and Benign Prostatic Hyperplasia (BPH) are progressive ailments resulting from androgenic imbalances and aging that can lead to serious long term complications. Objective of this study was to determine the relationship between prostate-specific antigens and testosterone hormone levels in patients with BPH before transurethral surgery.

Materials And Methods: This case control study was done on 112 serum samples collected from two secondary care centres in Khartoum, Sudan.

Intelligent Mechanisms of Macrophage Apoptosis Subversion by .

Macrophages are one of the first innate defense barriers and play an indispensable role in communication between innate and adaptive immune responses, leading to restricted () infection. The macrophages can undergo programmed cell death (apoptosis), which is a crucial step to limit the intracellular growth of bacilli by liberating them into extracellular milieu in the form of apoptotic bodies. These bodies can be taken up by the macrophages for the further degradation of bacilli or by the dendritic cells, thereby leading to the activation of T lymphocytes.

Human cytomegalovirus-encoded MicroRNAs: A master regulator of latent infection.

Human cytomegalovirus (HCMV) can modulate the host cell microenvironment to cause latent infection and is therefore considered a major health concern in immunocompromised patients. HCMV-encoded microRNAs (miRs) have emerged as a key player in regulating the expression of the host cell and viral genes to induce latent infection. HCMV-encoded miRs can inhibit antiviral immune responses, such as proinflammatory mediators production, antigenic presentation, and apoptosis.

Healthy CD4+ T lymphocytes are not affected by targeted therapies against the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia.

An attractive molecular target for novel anti-cancer therapies is the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway which is commonly deregulated in many types of cancer. Nevertheless, the effects of PI3K/Akt/mTOR inhibitors on T lymphocytes, a key component of immune responses, have been seldom explored. In this study we investigated the effects on human CD4+ T-cells of a panel of PI3K/Akt/mTOR inhibitors: BGT226, Torin-2, MK-2206, and ZSTK474.

The novel dual PI3K/mTOR inhibitor NVP-BGT226 displays cytotoxic activity in both normoxic and hypoxic hepatocarcinoma cells.

Hepatocellular carcinoma (HCC) is one of the most common lethal human malignancies worldwide and its advanced status is frequently resistant to conventional chemotherapeutic agents and radiation. We evaluated the cytotoxic effect of the orally bioavailable dual PI3K/mTOR inhibitor, NVP-BGT226, on a panel of HCC cell lines, since hyperactivated PI3K/Akt/mTOR signaling pathway could represent a biomolecular target for Small Inhibitor Molecules in this neoplasia. We analyzed the drug activity in both normoxia and hypoxia conditions, the latter playing often a relevant role in the induction of chemoresistance and angiogenesis.