The juxtamembrane sequence of small ankyrin 1 mediates the binding of its cytoplasmic domain to SERCA1 and is required for inhibitory activity.

Sarcoplasmic/endoplasmic reticulum Ca-ATPase1 (SERCA1) is responsible for the clearance of cytosolic Ca in skeletal muscle. Due to its vital importance in regulating Ca homeostasis, the regulation of SERCA1 has been intensively studied. Small ankyrin 1 (sAnk1, Ank1.

Colistin antibacterial activity, clinical effectiveness, and mechanisms of intrinsic and acquired resistance.

Following a period of disuse owing to the emergence of multidrug-resistant Gram-negative bacteria, colistin has regained global attention as an antibiotic of last resort. The resurgence in its utilization has led to a concurrent increase in acquired resistance, presenting a significant challenge in clinical treatment. Predominantly, resistance mechanisms involve alterations in the lipid A component of the lipopolysaccharide (LPS) structure.

Potential therapeutic effect of dimethyl fumarate on Treg/Th17 cell imbalance in biliary atresia.

The imbalance between Tregs and proinflammatory Th17 cells in children with biliary atresia (BA) causes immune damage to cholangiocytes. Dimethyl fumarate (DMF), an immunomodulatory drug, regulates the Treg/Th17 balance in diseases like multiple sclerosis (MS). This study explores DMF's effect on Treg/Th17 balance in BA and its potential mechanism.

TARGETING LUNG HEME IRON BY AEROSOL HEMOPEXIN ADMINSTRATION IN SICKLE CELL DISEASE PULMONARY HYPERTENSION.

Lung tissue from human patients and murine models of sickle cell disease pulmonary hypertension (SCD-PH) show perivascular regions with excessive iron accumulation. The iron accumulation arises from chronic hemolysis and extravasation of hemoglobin (Hb) into the lung adventitial spaces, where it is linked to nitric oxide depletion, oxidative stress, inflammation, and tissue hypoxia, which collectively drive SCD-PH. Here, we tested the hypothesis that intrapulmonary delivery of hemopexin (Hpx) to the deep lung is effective at scavenging heme-iron and attenuating the progression of SCD-PH.

Therapeutic outcomes and safety of radiofrequency ablation for primary papillary thyroid carcinoma: A game-changing meta-analysis.

Background: Radiofrequency ablation (RFA) is an emerging treatment option for small, low-risk papillary thyroid carcinoma (PTC). This systematic review and meta-analysis aimed to evaluate and compare the efficacy and safety profiles of RFA for primary T1a vs. T1b PTC.

CircKIAA0182 Enhances Lung Cancer Progression and Chemoresistance through Interaction with YBX1.

Lung cancer, particularly non-small cell lung cancer (NSCLC), remains a leading cause of cancer-related mortality. Resistance to platinum-based chemotherapy, such as cisplatin, significantly limits treatment efficacy. Circular RNAs (circRNAs) have emerged as key regulators of cancer progression and chemotherapy resistance due to their stable structure, which protects them from degradation.

Structures and mRNP remodeling mechanism of the TREX-2 complex.

mRNAs are packaged with proteins into messenger ribonucleoprotein complexes (mRNPs) in the nucleus. mRNP assembly and export are of fundamental importance for all eukaryotic gene expression. Before export to the cytoplasm, mRNPs undergo dynamic remodeling governed by the DEAD-box helicase DDX39B (yeast Sub2).

A forward genetic screen identifies potassium channel essentiality in SHH medulloblastoma maintenance.

Distinguishing tumor maintenance genes from initiation, progression, and passenger genes is critical for developing effective therapies. We employed a functional genomic approach using the Lazy Piggy transposon to identify tumor maintenance genes in vivo and applied this to sonic hedgehog (SHH) medulloblastoma (MB). Combining Lazy Piggy screening in mice and transcriptomic profiling of human MB, we identified the voltage-gated potassium channel KCNB2 as a candidate maintenance driver.

MicroRNAs' Significance in Retinoblastoma Diagnosis and Treatment: The Little Heroes.

One in 16, 000 live births is affected by the retinal tumor RB (retinoblastoma), which is frequently found in a child's early years. Both of the RB1 alleles that have been locally mutated in the affected retina are present in 60 percent of cases. Retinoblastoma (RB) can be detected using a variety of techniques, including imaging of the brain and orbits, eye examinations under anesthesia (EUAs), and the discovery of cell-free tumor DNA in samples of aqueous humor or plasma.

Nitro-fatty acids modulate germination onset through S-nitrosothiol metabolism.

-Nitro-fatty acids (NO2-FAs) have emerged as key components of nitric oxide (NO) signalling in eukaryotes. We previously described how nitro-linolenic acid (NO2-Ln), the major NO2-FA detected in plants, regulates S-nitrosoglutathione (GSNO) levels in Arabidopsis (Arabidopsis thaliana). However, the underlying molecular mechanisms remain undefined.

A-kinase anchor protein 12 promotes oligodendrogenesis and cognitive recovery in carbon monoxide therapy for traumatic brain injury.

Therapeutic drug development for central nervous system injuries, such as traumatic brain injury (TBI), presents significant challenges. TBI results in primary mechanical damage followed by secondary injury, leading to cognitive dysfunction and memory loss. Our recent study demonstrated the potential of carbon monoxide-releasing molecules (CORMs) to improve TBI recovery by enhancing neurogenesis.

Flunarizine as a Candidate for Drug Repurposing Against Human Pathogenic Mammarenaviruses.

Lassa fever (LF), a viral hemorrhagic fever disease with a case fatality rate that can be over 20% among hospitalized LF patients, is endemic to many West African countries. Currently, no vaccines or therapies are specifically licensed to prevent or treat LF, hence the significance of developing therapeutics against the mammarenavirus Lassa virus (LASV), the causative agent of LF. We used in silico docking approaches to investigate the binding affinities of 2015 existing drugs to LASV proteins known to play critical roles in the formation and activity of the virus ribonucleoprotein complex (vRNP) responsible for directing replication and transcription of the viral genome.

Monovalent Lectin Microvirin Utilizes Hydropathic Recognition of HIV-1 Env for Inhibition of Virus Cell Infection.

Microvirin is a lectin molecule known to have monovalent interaction with glycoprotein gp120. A previously reported high-resolution structural analysis defines the mannobiose-binding cavity of Microvirin. Nonetheless, structure does not directly define the energetics of binding contributions of protein contact residues.

Exploiting the Achilles' Heel of Viral RNA Processing to Develop Novel Antivirals.

Treatment options for viral infections are limited and viruses have proven adept at evolving resistance to many existing therapies, highlighting a significant vulnerability in our defenses. In response to this challenge, we explored the modulation of cellular RNA metabolic processes as an alternative paradigm to antiviral development. Previously, the small molecule 5342191 was identified as a potent inhibitor of HIV-1 replication by altering viral RNA accumulation at doses that minimally affect host gene expression.

Clinical Characteristics and Outcomes in Patients with Chronic HBV Infection and Hospitalized for COVID-19 Pneumonia: A Retrospective Cohort Study.

The effects of a concomitant infection of hepatitis B virus (HBV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are still debated, with a recognized major risk of HBV reactivation during immune-suppressive treatments. The aim of this study was to determine the prevalence and predictive factors of HBV reactivation in a cohort of hospitalized patients with coronavirus disease 2019 (COVID-19) and a current or past hepatitis B infection. In a monocentric retrospective observational study, we enrolled all consecutive hospital admitted patients with COVID-19 pneumonia and a positive HBV serology (N = 84) in our Infectious Diseases Unit from April 2021 to December 2023.

Water-Soluble Vitamins: Hypo- and Hypervitaminosis in Pediatric Population.

Background/objectives: Water-soluble vitamins, comprising the B-complex vitamins and vitamin C, are essential for normal growth, cellular metabolism, and immune function in pediatric populations. Due to limited storage in the body, these vitamins require consistent intake to prevent deficiencies. Pediatric populations, particularly infants and young children, face a heightened risk of both deficiency and, in rare cases, toxicity due to varying dietary intake and increased developmental needs.

Liposomal Formulation of Hydroxychloroquine Can Inhibit Autophagy In Vivo.

Preclinical studies have shown that the anti-malarial drug hydroxychloroquine (HCQ) improves the anti-cancer effects of various therapeutic agents by impairing autophagy. These findings are difficult to translate in vivo as reaching an effective HCQ concentration at the tumor site for extended times is challenging. Previously, we found that free HCQ in combination with gefitinib (Iressa, ZD1839) significantly reduced tumor volume in immunocompromised mice bearing gefitinib-resistant JIMT-1 breast cancer xenografts.

Investigation of Novel Aronia Bioactive Fraction-Alginic Acid Nanocomplex on the Enhanced Modulation of Neuroinflammation and Inhibition of Aβ Aggregation.

Background/objectives: Aronia extract or its active compounds, especially anthocyanin, have shown potential for Alzheimer's disease (AD)-related pathologies, including neuroinflammation, fibrillogenesis of amyloid beta (Aβ), and cognitive impairment. However, there was still concern about their structural instability in vivo and in vitro. To solve the instability of anthocyanins, we combined aronia bioactive factions (ABFs) and alginic acid via electrostatic molecular interactions and created an ABF-alginic acid nanocomplex (AANCP).

Fucoidan Oligosaccharide Supplementation Relieved Kidney Injury and Modulated Intestinal Homeostasis in D-Galactose-Exposed Rats.

A fucoidan oligosaccharide (FOS), a potent compound derived from algae, is known for its diverse biological activities, including prebiotic activity, anticancer activity, and antioxidative properties, and has demonstrated supportive therapeutic effects in treating kidney ailments. This study was conducted to explore the protective influence of FOS on kidney damage due to aging induced by D-galactose in Sprague Dawley (SD) rats. The low-dose FOS group was administered FOS (100 mg/kg) by gavage, and the high-FOS group received FOS (200 mg/kg) by gavage.

Effect of a Novel Food Rich in Miraculin on the Intestinal Microbiome of Malnourished Patients with Cancer and Dysgeusia.

Background/objectives: Dysgeusia contributes to malnutrition and worsens the quality of life of patients with cancer. Despite the different strategies, there is no effective treatment for patients suffering from taste disorders provided by the pharmaceutical industry. Therefore, we developed a novel strategy for reducing side effects in cancer patients by providing a novel food supplement with the taste-modifying glycoprotein miraculin, which is approved by the European Union, as an adjuvant to medical-nutritional therapy.

Molecular Mechanisms Underlying Neuroinflammation Intervention with Medicinal Plants: A Critical and Narrative Review of the Current Literature.

Neuroinflammation is a key factor in the progression of neurodegenerative diseases, driven by the dysregulation of molecular pathways and activation of the brain's immune system, resulting in the release of pro-inflammatory and oxidative molecules. This chronic inflammation is exacerbated by peripheral leukocyte infiltration into the central nervous system. Medicinal plants, with their historical use in traditional medicine, have emerged as promising candidates to mitigate neuroinflammation and offer a sustainable alternative for addressing neurodegenerative conditions in a green healthcare framework.

Revisiting ABC Transporters and Their Clinical Significance in Glioblastoma.

: The multiple drug-resistant phenomenon has long since plagued the effectiveness of various chemotherapies used in the treatment of patients with glioblastoma (GBM), which is still incurable to this day. ATP-binding cassette (ABC) transporters function as drug transporters and have been touted to be the main culprits in developing resistance to xenobiotic drugs in GBM. : This review systematically analyzed the efficacy of ABC transporters against various anticancer drugs from 16 studies identified from five databases (PubMed, Medline, Embase, Scopus, and ScienceDirect).

-Lyophilized Fruit Extract Attenuated Acute Redox-Homeostatic Imbalance via Mutagenic and Oxidative Stress Modulation in Mice Model on Gentamicin-Induced Nephrotoxicity.

Gentamicin (GM) administration is associated with decreased metabolism, increased oxidative stress, and induction of nephrotoxicity. L., containing flavonoids, anthocyanins, and phytosterols, possesses antioxidant and anti-inflammatory potential.

Therapeutic Efficacy of 's Oil and Ethanol Extract in Regulation of the Neuroinflammation, Histopathological Alterations, Oxidative Stress, and Restoring Balance Treg Cells Expressing FoxP3+ in a Rat Model of Epilepsy.

: Despite the availability of antiepileptic drugs (AEDs) that can manage seizures, they often come with cognitive side effects. Furthermore, the role of oxidative stress and neuroinflammatory responses in epilepsy and the limitations of current AEDs necessitate exploring alternative therapeutic options. Medicinal plants, e.