26,048 results match your criteria: "Faculty of Pharmacy and Biochemistry; Hospital de Clinicas[Affiliation]"

Synthesis and biological assessment of BUB1B inhibitors for the treatment of clear cell renal cell carcinoma.

Eur J Med Chem

January 2025

Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE, 17165, Sweden; Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, SE1 9RT, UK. Electronic address:

Clear cell renal cell carcinoma (ccRCC) presents substantial therapeutic challenges due to its molecular heterogeneity, limited response to conventional therapies, and widespread drug resistance. Recent advancements in molecular research have identified novel targets, such as BUB1B, which has been identified through global transcriptomic profiling and gene co-expression network analysis as critical in ccRCC progression. In this study, we synthesized 40 novel derivatives of TG-101209 to modulate BUB1B expression and activity, leading to the induction of apoptosis in Caki-1 cells.

View Article and Find Full Text PDF

Macrolide resistance due to (55).

Microbiol Spectr

January 2025

Institute for Microbial Systems and Society, Faculty of Science, University of Regina, Regina, Saskatchewan, Canada.

Unlabelled: Antimicrobial resistance (AMR) is a global threat. The identification and characterization of novel resistance genes is integral to AMR surveillance. The (55) gene was originally identified through whole genome sequencing of macrolide-resistant strains of .

View Article and Find Full Text PDF

Cancer is one of the most devastating illnesses in the world, impacting millions of individuals every year. Despite various therapies, the final effect is unsatisfactory. Chemotherapy currently dominates as the primary option of treatment.

View Article and Find Full Text PDF

Molecular Targets and Small Molecules Modulating Acetyl Coenzyme A in Physiology and Diseases.

ACS Pharmacol Transl Sci

January 2025

Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Science Center, Amarillo, Texas 79106, United States.

Acetyl coenzyme A (acetyl-CoA), a pivotal regulatory metabolite, is a product of numerous catabolic reactions and a substrate for various anabolic responses. Its role extends to crucial physiological processes, such as glucose homeostasis and free fatty acid utilization. Moreover, acetyl-CoA plays a significant part in reshaping the metabolic microenvironment and influencing the progression of several diseases and conditions, including cancer, insulin resistance, diabetes, heart failure, fear, and neuropathic pain.

View Article and Find Full Text PDF

The most common type of liver cancer is hepatocellular carcinoma (HCC), accounting for 75-85% of cases. Despite its associated side effects, sorafenib remains the standard treatment for HCC. Given the critical need to improve therapeutic efficacy while minimizing adverse effects, alternative drugs must be thoroughly investigated.

View Article and Find Full Text PDF

In recent decades, the common and the tropical bed bugs have experienced a resurgence in many parts of the world. The evolution of insecticide resistance in bed bug populations is considered a significant factor contributing to this resurgence. We analyzed samples of Cimex lectularius L.

View Article and Find Full Text PDF

The hydrothermal synthesis is presented of copper-doped carbon dots (Cu-CDs) from citric acid, urea, and copper chloride, resulting in blue-fluorescent particles with stable emission at 438 nm when excited at 340 nm. Through comprehensive spectroscopic and microscopic characterization (FTIR, XPS, UV, and HRTEM), the Cu-CDs demonstrated remarkable stability across varying pH levels, ionic strengths, temperatures, and UV exposure. Notably, Cu-CDs exhibit ultra-sensitive and selective detection of hexavalent chromium [Cr(VI)] ions in aqueous environments driven by fluorescence quenching.

View Article and Find Full Text PDF

Extracellular vesicles (EVs) are nanosized lipid bilayer particles released by various cellular organisms that carry an array of bioactive molecules. EVs have diagnostic potential, as they play a role in intercellular interspecies communication, and could be applied in drug delivery. In contrast to mammalian cell-derived EVs, the study of EVs from bacteria, particularly Gram-positive bacteria, received less research attention.

View Article and Find Full Text PDF

This study compared two Annona squamosa L. cultivars, Abdelrazik (Annona A.) and Balady (Annona B.

View Article and Find Full Text PDF

Background: Oxidative stress is strongly linked to neurodegeneration through the activation of c-Abl kinase, which arrests α-synuclein proteolysis by interacting with parkin interacting substrate (PARIS) and aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2). This activation, triggered by ataxia-telangiectasia mutated (ATM) kinase, leads to dopaminergic neuron loss and α-synuclein aggregation, a critical pathophysiological aspect of Parkinson's disease (PD). To halt PD progression, pharmacological inhibition of c-Abl kinase is essential.

View Article and Find Full Text PDF

Inducing apoptosis in acute myeloid leukemia; mechanisms and limitations.

Heliyon

January 2025

Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.

Acute myeloid leukemia is the expansion of leukemic stem cells which might originate from a stem cell or a progenitor which has acquired self-renewal capacity. An aggregation of leukemic blasts in bone marrow, peripheral blood, and extramedullary tissue will result in acute myeloid leukemia. The main difficulty in treating acute myeloid leukemia is multidrug resistance, leading to treatment failure.

View Article and Find Full Text PDF

Asparagine-linked glycosylation (N-glycosylation) is a common co- and post-translational modification that refers to the addition of complex carbohydrates, called N-linked glycans (N-glycans), to asparagine residues within defined sequons of polypeptide acceptors. Some N-glycans can be modified by the addition of phosphate moieties to their monosaccharide residues, thus forming phospho-N-glycans (PNGs). The most prominent such carbohydrate modification is mannose-6-phosphate (M6P) which plays a well-established role in trafficking of acid hydrolases to lysosomes.

View Article and Find Full Text PDF

Background: The WHO considers anemia in pregnancy a severe public health issue when prevalence surpasses 40%. In response, we conducted a systematic review and meta-analysis to examine anemia among pregnant women in Egypt, focusing on its prevalence, determinants, and associated complications.

Methods: We conducted a systematic literature search for studies published between January 1, 2010, and August 18, 2024, to identify studies from Egypt reporting on anemia in pregnant women, including its prevalence, associated determinants, and complications.

View Article and Find Full Text PDF

Catalytic-independent functions of the Integrator-PP2A complex (INTAC) confer sensitivity to BET inhibition.

Nat Chem Biol

January 2025

Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Medical Epigenetics, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

Chromatin and transcription regulators are critical to defining cell identity through shaping epigenetic and transcriptional landscapes, with their misregulation being closely linked to oncogenesis. Pharmacologically targeting these regulators, particularly the transcription-activating BET proteins, has emerged as a promising approach in cancer therapy, yet intrinsic or acquired resistance frequently occurs, with poorly understood mechanisms. Here, using genome-wide CRISPR screens, we find that BET inhibitor efficacy in mediating transcriptional silencing and growth inhibition depends on the auxiliary/arm/tail module of the Integrator-PP2A complex (INTAC), a global regulator of RNA polymerase II pause-release dynamics.

View Article and Find Full Text PDF

Glioblastoma multiforme (GBM) is the most prevalent, treatment-resistant, and fatal form of brain malignancy. It is characterized by genetic heterogeneity, and an infiltrative nature, and GBM treatment is highly challenging. Despite multimodal therapies, clinicians lack efficient prognostic and predictive markers.

View Article and Find Full Text PDF

Neuroprotective role of mirabegron: Targeting beta-3 adrenergic receptors to alleviate ulcerative colitis-associated cognitive impairment.

Biomed Pharmacother

January 2025

Pharmacology, Toxicology and Biochemistry Department, Faculty of Pharmacy, Future University in Egypt (FUE), Cairo, Egypt; Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

While cognitive impairment has been documented in ulcerative colitic patients, the possible influence of central β3-adrenergic receptor (β3-AR) signaling on this extraintestinal manifestation remains unclear. Previously, we identified an imperative role for mirabegron (MA) as an agonist of β3-AR, in decreasing the BACE-1/beta-amyloid (Aβ) cue in the colons of UC rats. Consequently, we investigated its therapeutic potential for alleviating cognitive impairment associated with UC.

View Article and Find Full Text PDF

Cyclooxygenase-2 (COX-2), a key enzyme in the inflammatory pathway, is the target for various nonsteroidal anti-inflammatory drugs (NSAIDs) and selective inhibitors known as coxibs. This study focuses on the development of novel imidazole derivatives as COX-2 inhibitors, utilizing a Structure-Activity Relationship (SAR) approach to enhance binding affinity and selectivity. Molecular docking was performed using Autodock Vina, revealing binding energies of -6.

View Article and Find Full Text PDF

Mycotoxin exposure from contaminated food is a significant global health issue, particularly among vulnerable children. Given limited data on mycotoxin exposure among Namibian children, this study investigated mycotoxin types and levels in foods, evaluated dietary mycotoxin exposure from processed cereal foods in children under age five from rural households in Oshana region, Namibia. Mycotoxins in cereal-based food samples (n = 162) (mahangu flour (n = 35), sorghum flour (n = 13), mahangu thin/thick porridge (n = 54), oshikundu (n = 56), and omungome (n = 4)) were determined by liquid chromatography-tandem mass spectrometry.

View Article and Find Full Text PDF

MircoRNAs predict and modulate responses to chemotherapy in leukemic patients.

Naunyn Schmiedebergs Arch Pharmacol

January 2025

Oral Biology Department, Faculty of Dentistry, Galala Plateau, Galala University, 15888), Attaka, Suez Governorate, Egypt.

Leukemia covers a broad category of cancer malignancies that specifically affect bone marrow and blood cells. While different kinds of leukemia have been identified, effective treatments are still lacking for most forms, and even those treatments considered effective can lead to relapses. MicroRNAs, or miRNAs, are short endogenous non-coding single-stranded RNAs that help control the epigenetics of gene expression.

View Article and Find Full Text PDF

Background: Bronchopulmonary dysplasia (BPD) is a chronic lung disease in premature infants caused by an imbalance between lung injury and lung repair in the developing immature lungs of the newborn. Pulmonary inflammation is an important feature in the pathogenesis of BPD. The aim of this study was to evaluate the relationship between the inflammatory microenvironment and the levels of visfatin and nesfatin-1, which are among the new adipocytokines, in BPD patients.

View Article and Find Full Text PDF

Cervical cancer ranks as the fourth most common cancer among women globally, posing a significant mortality risk. Persistent infection with high-risk human papillomavirus (HPV) is the primary instigator of cervical cancer development, often alongside coinfection with other viruses, precipitating various malignancies. This study aimed to explore recent biotechnological advances in understanding HPV infection dynamics, host interactions, and its role in oncogenesis.

View Article and Find Full Text PDF

Maejo 341 Sweet potato (MSP) is a new purple sweet potato variety cultivated in Northern Thailand, but its health benefits are unknown. This study aimed to investigate its antioxidant, anti-inflammatory, and anti-osteoporotic activities, as well as its anthocyanin content. The peel and flesh of MSP were extracted with ethanol and water.

View Article and Find Full Text PDF

Purpose: Intravitreal bevacizumab has been utilized to mitigate radiation retinopathy, yet the potential role of intravitreal melatonin for its prevention remains unexplored. This study aims to evaluate and compare the efficacy of intravitreal melatonin and bevacizumab in preventing radiation retinopathy in an experimental animal model.

Materials And Methods: Twelve healthy male New Zealand white rabbits ( = 24 eyes) received a single 3000 cGy irradiation dose in both eyes.

View Article and Find Full Text PDF

The etiology of rheumatoid arthritis (RA) is multifaceted. One of the hypothesized pathways that results in the progression of RA is regulatory T cell (Treg) dysfunction. The pro-osteoclastogenic and immunogenic characteristics of microribonucleic acid (microRNA)-21 (miR-21) suggest its role in RA progression.

View Article and Find Full Text PDF