Machine Learning Reveals Signatures of Promiscuous Microbial Amidases for Micropollutant Biotransformations.

Organic micropollutants, including pharmaceuticals, personal care products, pesticides, and food additives, are widespread in the environment, causing potentially toxic effects. Human waste is a direct source of micropollutants, with the majority of pharmaceuticals being excreted through urine. Urine contains its own microbiota with the potential to catalyze micropollutant biotransformations.

Lactate dehydrogenase B noncanonically promotes ferroptosis defense in KRAS-driven lung cancer.

Ferroptosis is an oxidative, non-apoptotic cell death frequently inactivated in cancer, but the underlying mechanisms in oncogene-specific tumors remain poorly understood. Here, we discover that lactate dehydrogenase (LDH) B, but not the closely related LDHA, subunits of active LDH with a known function in glycolysis, noncanonically promotes ferroptosis defense in KRAS-driven lung cancer. Using murine models and human-derived tumor cell lines, we show that LDHB silencing impairs glutathione (GSH) levels and sensitizes cancer cells to blockade of either GSH biosynthesis or utilization by unleashing KRAS-specific, ferroptosis-catalyzed metabolic synthetic lethality, culminating in increased glutamine metabolism, oxidative phosphorylation (OXPHOS) and mitochondrial reactive oxygen species (mitoROS).

Inhibition of LDHB suppresses the metastatic potential of lung cancer by reducing mitochondrial GSH catabolism.

Metastasis, the leading cause of cancer death, is closely linked to lactate metabolism. Our study aimed to investigate the role of lactate dehydrogenase B (LDHB), which mainly catalyzes the conversion of lactate to pyruvate, in the metastatic potential of lung cancer. We found that LDHB silencing reduced the invasion and migration ability of lung cancer cells in vitro.

Impact of Illness Perception in Overweight and Obesity on Bio-Functional Age and Eating/Movement Behavior-A Follow-Up Study.

Background: Despite the widespread prevalence of obesity and its potential adverse impacts on health, the majority of interventions aimed at weight loss stay ineffective. This study aimed to assess illness perception in people with overweight/obesity and its impact on bio-functional age (BFA) and cognitive patterns governing eating and movement behavior.

Methods: A total of 40 subjects from the original overweight/obesity subcohort of the Bern Cohort Study 2014 (BeCS14) were included and assessed for a follow-up from 2019-11-29 to 2020-07-14.

Assessing the metastatic potential of circulating tumor cells using an organ-on-chip model.

Metastatic lung cancer remains a leading cause of death worldwide, with its intricate metastatic cascade posing significant challenges to researchers and clinicians. Despite substantial progress in understanding this cascade, many aspects remain elusive. Microfluidic-based vasculature-on-chip models have emerged as powerful tools in cancer research, enabling the simulation of specific stages of tumor progression.

Crispr-mediated genome editing reveals a preponderance of non-oncogene addictions as targetable vulnerabilities in pleural mesothelioma.

Pleural mesothelioma (PM) is an aggressive cancer with limited treatment options. In particular, the frequent loss of tumor suppressors, a key oncogenic driver of the disease that is therapeutically intractable, has hampered the development of targeted cancer therapies. Here, we interrogate the PM genome using CRISPR-mediated gene editing to systematically uncover PM cell susceptibilities and provide an evidence-based rationale for targeted cancer drug discovery.

Chemotherapy increases CDA expression and sensitizes malignant pleural mesothelioma cells to capecitabine treatment.

The combination of cisplatin and pemetrexed remains the gold standard chemotherapy for malignant pleural mesothelioma (MPM), although resistance and poor response pose a significant challenge. Cytidine deaminase (CDA) is a key enzyme in the nucleotide salvage pathway and is involved in the adaptive stress response to chemotherapy. The cytidine analog capecitabine and its metabolite 5'-deoxy-5-fluorocytidine (5'-DFCR) are converted via CDA to 5-fluorouracil, which affects DNA and RNA metabolism.

A Retrospective Analysis of Systemic Infection in Children.

Systemic infection, also known as cat-scratch disease (CSD), presents a diagnostic challenge due to the variability of clinical manifestations and the potential for serological cross-reactivity with other organisms. This study aimed to retrospectively analyze the epidemiological, clinical, laboratory, and imaging characteristics of pediatric patients diagnosed with systemic infection, to improve understanding and facilitate timely diagnosis and treatment. We conducted a 10-year retrospective study at the "Louis Turcanu" Children's Emergency Hospital and private clinics in Timisoara, Romania, reviewing records for confirmed cases of infection from January 2014 to January 2024.

Understanding the Impact of COVID-19 on Roma Vulnerable Communities in Western Romania: Insights and Predictive Factors from a Retrospective Study.

Background: The COVID-19 pandemic disproportionately affected vulnerable populations like Roma patients in Western Romania due to marginalization and limited healthcare access.

Methods: A retrospective study analyzed COVID-19 cases between March 2020 and August 2022 using data from the Directorate of Public Health in Timis county. Demographic, epidemiological, clinical, and laboratory data were assessed, along with risk factors and biomarkers for ICU admission and mortality prediction.

A Retrospective Analysis from Western Romania Comparing the Treatment and Survivability of p16-Positive versus p16-Negative Oropharyngeal Cancer.

Background: Oropharyngeal cancer is a global health concern due to its multifaceted nature. Recent molecular studies have linked p16 overexpression, associated with the human papillomavirus, to oropharyngeal cancer and its prognostic implications.

Materials And Methods: This retrospective study in Western Romania examined 60 patients, categorizing them based on p16 biomarker status: 28 were p16 positive, and 32 were p16 negative.

Microbial Biocatalysis within Us: The Underexplored Xenobiotic Biotransformation Potential of the Urinary Tract Microbiota.

Enzymatic biotransformation of xenobiotics by the human microbiota mediates diet-drug-microbe-host interactions and affects human health. Most research on xenobiotics has focused on the gut microbiota while neglecting other body sites, yet over two-thirds of pharmaceuticals are primarily excreted in urine. As a result, the urinary microbiota is exposed to many xenobiotics in much higher concentrations than in the gut.

The secondary injury cascade after spinal cord injury: an analysis of local cytokine/chemokine regulation.

After spinal cord injury, there is an extensive infiltration of immune cells, which exacerbates the injury and leads to further neural degeneration. Therefore, a major aim of current research involves targeting the immune response as a treatment for spinal cord injury. Although much research has been performed analyzing the complex inflammatory process following spinal cord injury, there remain major discrepancies within previous literature regarding the timeline of local cytokine regulation.

An optimized protocol for the generation and monitoring of conditional orthotopic lung cancer in the KP mouse model using an adeno-associated virus vector compatible with biosafety level 1.

Background: The inducible Kras/p53 lung adenocarcinoma mouse model, which faithfully recapitulates human disease, is routinely initiated by the intratracheal instillation of a virus-based Cre recombinase delivery system. Handling virus-based delivery systems requires elevated biosafety levels, e.g.

relative abundance in shower hose biofilms is associated with specific microbiome members.

are natural inhabitants of building plumbing biofilms, where interactions with other microorganisms influence their survival, proliferation, and death. Here, we investigated the associations of with bacterial and eukaryotic microbiomes in biofilm samples extracted from 85 shower hoses of a multiunit residential building. spp.

A multiplex inhalation platform to model like aerosol delivery in a breathing lung-on-chip.

Prolonged exposure to environmental respirable toxicants can lead to the development and worsening of severe respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD) and fibrosis. The limited number of FDA-approved inhaled drugs for these serious lung conditions has led to a shift from towards the use of alternative human-relevant models to better predict the toxicity of inhaled particles in preclinical research. While there are several inhalation exposure models for the upper airways, the fragile and dynamic nature of the alveolar microenvironment has limited the development of reproducible exposure models for the distal lung.

Gait analysis in swine, sheep, and goats after neurologic injury: a literature review.

Medical research on neurologic ailments requires representative animal models to validate treatments before they are translated to human clinical trials. Rodents are the predominant animal model used in neurological research despite limited anatomic and physiologic similarities to humans. As a result, functional testing designed to assess locomotor recovery after neurologic impairment is well established in rodent models.

MEK1 drives oncogenic signaling and interacts with PARP1 for genomic and metabolic homeostasis in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a lethal malignancy etiologically caused by asbestos exposure, for which there are few effective treatment options. Although asbestos carcinogenesis is associated with reactive oxygen species (ROS), the bona fide oncogenic signaling pathways that regulate ROS homeostasis and bypass ROS-evoked apoptosis in MPM are poorly understood. In this study, we demonstrate that the mitogen-activated protein kinase (MAPK) pathway RAS-RAF-MEK-ERK is hyperactive and a molecular driver of MPM, independent of histological subtypes and genetic heterogeneity.

Esophageal ulcer associated with mild hemophilia A: case report.

In this paper, we present the case of a 68-year-old male with personal medical history of coagulopathy issues, who presented to our Emergency Room (Emergency County Hospital, Arad, Romania) with bleeding of the superior tract of the digestive system; the case was difficult to manage, thus warranting the intervention of the Department of Gastroenterology. Endoscopy was performed to localize the site of bleeding and to stop the hemorrhage. This procedure was not successful.

An oncogene addiction phosphorylation signature and its derived scores inform tumor responsiveness to targeted therapies.

Purpose: Oncogene addiction provides important therapeutic opportunities for precision oncology treatment strategies. To date the cellular circuitries associated with driving oncoproteins, which eventually establish the phenotypic manifestation of oncogene addiction, remain largely unexplored. Data suggest the DNA damage response (DDR) as a central signaling network that intersects with pathways associated with deregulated addicting oncoproteins with kinase activity in cancer cells.

Non-genetic adaptive resistance to KRAS inhibition: EMT is not the only culprit.

Adaptions to therapeutic pressures exerted on cancer cells enable malignant progression of the tumor, culminating in escape from programmed cell death and development of resistant diseases. A common form of cancer adaptation is non-genetic alterations that exploit mechanisms already present in cancer cells and do not require genetic modifications that can also lead to resistance mechanisms. Epithelial-to-mesenchymal transition (EMT) is one of the most prevalent mechanisms of adaptive drug resistance and resulting cancer treatment failure, driven by epigenetic reprogramming and EMT-specific transcription factors.

Dissecting the Immunological Profiles in -Amplified LUSC through Integrative Multi-Scale Analyses.

The histone H3 lysine 36 (H3K36) methyltransferase , a neighboring gene of , has been identified as a critical genetic driver of lung squamous cell carcinoma (LUSC). However, the molecular characteristics, especially the immunological roles of in driving carcinogenesis, are poorly understood. In this study, we systematically integrated multi-omics data (e.

Schedule-Dependent Treatment Increases Chemotherapy Efficacy in Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare but aggressive thoracic malignancy with limited treatment options. One of the standard treatments for MPM is chemotherapy, which consists of concurrent treatment with pemetrexed and cisplatin. Pemetrexed limits tumor growth by inhibiting critical metabolic enzymes involved in nucleotide synthesis.