Genomic Characterization of Carbapenemase-Producing Enterobacteriaceae from Clinical and Epidemiological Human Samples.

: Infections caused by multidrug-resistant (MDR)bacteria pose a significant public health threat by worsening patient outcomes, contributing to hospital outbreaks, and increasing health and economic burdens. Advanced genomic tools enhance the detection of resistance genes, virulence factors, and high-risk clones, thus improving the management of MDR infections. In the Autonomous Community of Aragon, the diversity and incidence of carbapenemase-producing Enterobacteriaceae (CPE) have increased during the last years.

Standardization of the Agar Plate Method for Bacteriophage Production.

The growing threat of antimicrobial resistance (AMR), exacerbated by the COVID-19 pandemic, highlights the urgent need for alternative treatments such as bacteriophage (phage) therapy. Phage therapy offers a targeted approach to combat bacterial infections, particularly those resistant to conventional antibiotics. This study aimed to standardize an agar plate method for high-mix, low-volume phage production, suitable for personalized phage therapy.

Dynamic Multilevel Regulation of EGFR, KRAS, and MYC Oncogenes: Driving Cancer Cell Proliferation Through (Epi)Genetic and Post-Transcriptional/Translational Pathways.

The epidermal growth factor receptor (EGFR) regulates gene expression through two primary mechanisms: as a growth factor in the nucleus, where it translocates upon binding its ligand, or via its intrinsic tyrosine kinase activity in the cytosol, where it modulates key signaling pathways such as RAS/MYC, PI3K, PLCγ, and STAT3. During tumorigenesis, these pathways become deregulated, leading to uncontrolled proliferation, enhanced migratory and metastatic capabilities, evasion of programmed cell death, and resistance to chemotherapy or radiotherapy. The and oncogenes are pivotal in tumorigenesis, driving processes such as resistance to apoptosis, replicative immortality, cellular invasion and metastasis, and metabolic reprogramming.

Association of Corticosteroid Inhaler Type with Saliva Microbiome in Moderate-to-Severe Pediatric Asthma.

: Metered-dose inhalers (MDIs) and dry powder inhalers (DPIs) are common inhaled corticosteroid (ICS) inhaler devices. The difference in formulation and administration technique of these devices may influence oral cavity microbiota composition. We aimed to compare the saliva microbiome in children with moderate-to-severe asthma using ICS via MDIs versus DPIs.

Potentials of Presepsin as a Novel Sepsis Biomarker in Critically Ill Adults: Correlation Analysis with the Current Diagnostic Markers.

Sepsis is a major cause of patient death in intensive care units (ICUs). Rapid diagnosis of sepsis assists in optimizing treatments and improves outcomes. Several biomarkers are employed to aid in the diagnosis, prognostication, severity grading, and sub-type discrimination of severe septic infections (SSIs), including current diagnostic parameters, hemostatic measures, and specific organ dysfunction markers.

Performance analysis of Leica Biosystems p16 monoclonal antibody in oropharyngeal squamous cell carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer death globally, with newly diagnosed oropharyngeal squamous cell carcinoma (OPSCC) cases rising to 54,000 in the US alone in the year 2022. Recently, human papilloma virus (HPV) infection was more prevalent in OPSCC patients than the traditionally known carcinogens such as tobacco or alcohol. HPV 16 is the most common causative HPV strain, which is found in 5-10% of HNSCC patients.

Comparative evaluation of antifungal susceptibility testing methods of invasive Candida species and detection of FKS genes mutations in caspofungin intermediate and resistant isolates.

Background: Fungal invasive infections caused by Candida species pose a substantial public health risk with limited therapeutic options. Antifungal susceptibility testing (AFST) is necessary to optimize the therapy. The study aimed to compare different AFST methods of Candida spp.

Engineering the future of medicine: Natural products, synthetic biology and artificial intelligence for next-generation therapeutics.

The eXchange Unit between Thiolation domains approach and artificial intelligence (AI)-driven tools like Synthetic Intelligence are transforming nonribosomal peptide synthetase and polyketide synthase engineering, enabling the creation of novel bioactive compounds that address critical challenges like antibiotic resistance and cancer. These innovations expand chemical space and optimize biosynthetic pathways, offering precise and scalable therapeutic solutions. Collaboration across synthetic biology, AI, and clinical research is essential to translating these breakthroughs into next-generation treatments and revolutionizing drug discovery and patient care.

Amoebas: the omnipotent organism and silent assassin.

Amoebas are characterized by their unique ability to exist both as free-living organisms and, occasionally, as parasites within host tissues, earning them the designation 'amphizoic amoebae'. While amoebic infections are less prevalent, their health impact can be tremendous, leading to several diseases. In low-income countries, poor sanitation and socioeconomic conditions significantly increase the risk of amoebic infections, particularly E.

Elevated uric acid levels, mortality and cognitive impairment in children with severe malaria.

We investigated the role of uric acid in the pathogenesis of severe malaria (SM) in two independent cohorts of children with SM. Hyperuricemia (blood uric acid ≥ 7 mg dl) was present in 25% of children with SM and was associated with increased in-hospital mortality and postdischarge mortality in both cohorts. Increased blood uric acid levels were also associated with worse scores in overall cognition in children with SM < 5 years old in both cohorts.

Curcumin enhances the anti-obesogenic activity of orlistat through SKN-1/NRF2-dependent regulation of nutrient metabolism in Caenorhabditis elegans.

Background: Metabolic dysregulation, a defining feature of obesity, disrupts essential signalling pathways involved in nutrient sensing and mitochondria homeostasis. The nuclear factor erythroid 2-related factor 2 (NRF-2) serves as a pivotal regulator of the cellular stress response, and recent studies have implicated it in the pathogenesis of obesity, diabetes, and metabolic syndrome. Curcumin, a polyphenolic compound derived from turmeric, has been identified as a potent activator of NRF-2.

Roles of human papillomavirus in cancers: oncogenic mechanisms and clinical use.

Human papillomaviruses, particularly high-risk human papillomaviruses, have been universally considered to be associated with the oncogenesis and progression of various cancers. The genome of human papillomaviruses is circular, double-stranded DNA that encodes early and late proteins. Each of the proteins is of crucial significance in infecting the epithelium of host cells persistently and supporting viral genome integrating into host cells.

First morphological and molecular characterisation of Spirometra mansoni (Cestoda, Diphyllobothriidae) in a domestic cat from Veracruz, Mexico.

Cestodes of the genus Spirometra are multi-host parasites that are the causative agents of spirometrosis in domestic and wild carnivores and sparganosis in humans, endemic diseases in tropical and subtropical regions. In domestic animals, the infection is usually asymptomatic or produces gastrointestinal signs such as vomiting and chronic diarrhoea. In humans, an incidental parasitosis develops where the plerocercoid can lodge in tissues and cause a variety of symptoms, including neuropathies, blindness, paralysis, and death.

Dermanyssus gallinae as a pathogen vector: Phylogenetic analysis and associated health risks in pigeons.

Dermanyssus gallinae (D. gallinae) is a nocturnal, blood-feeding ectoparasite that primarily infests poultry, causing significant economic losses. This study aimed to identify poultry red mites and detect associated pathogens using morphological and molecular techniques.

Comparison of Liquid-Based Cytology EASYPREP and SurePath for Detection of High-Risk HPV Genotypes.

Objective: Molecular testing for high-risk human papillomavirus (hrHPV) genotypes is important for cervical cancer screening. In this study, we compared the HPV detection rates using real-time PCR in cervical samples collected using two different liquid-based cytology (LBC) kits.

Methods: Cervical swab specimens were prospectively collected using the SurePath and EASYPREP collection kits.

Plant secondary metabolites against biotic stresses for sustainable crop protection.

Sustainable agriculture practices are indispensable for achieving a hunger-free world, especially as the global population continues to expand. Biotic stresses, such as pathogens, insects, and pests, severely threaten global food security and crop productivity. Traditional chemical pesticides, while effective, can lead to environmental degradation and increase pest resistance over time.

Structure-guided discovery of viral proteins that inhibit host immunity.

Viruses encode proteins that inhibit host defenses, but sifting through the millions of available viral sequences for immune-modulatory proteins has been so far impractical. Here, we develop a process to systematically screen virus-encoded proteins for inhibitors that physically bind host immune proteins. Focusing on Thoeris and CBASS, bacterial defense systems that are the ancestors of eukaryotic Toll/interleukin-1 receptor (TIR) and cyclic GMP-AMP synthase (cGAS) immunity, we discover seven families of Thoeris and CBASS inhibitors, encompassing thousands of genes widespread in phages.

Inula japonica Thunb. and its active compounds ameliorate airway inflammation by suppressing JAK-STAT signaling.

Asthma, a chronic inflammatory disease, remains a global health challenge due to its complex pathophysiology and the limited treatment efficacy. This study explored the effect of Inula japonica Thunb. water extract (IJW) on asthma and its protective mechanisms.

Synthesis and preclinical evaluation of tigilanol tiglate analogs as latency-reversing agents for the eradication of HIV.

Tigilanol tiglate (EBC-46) is a selective modulator of protein kinase C (PKC) isoforms that is Food and Drug Administration (FDA) approved for the treatment of mast cell tumors in canines with up to an 88% cure rate. Recently, it has been FDA approved for the treatment of soft tissue sarcomas in humans. The role of EBC-46 and, especially, its analogs in efforts to eradicate HIV, treat neurological and cardiovascular disorders, or enhance antigen density in antigen-targeted chimeric antigen receptor-T cell and chimeric antigen receptor-natural killer cell immunotherapies has not been reported.

Occurrence of virulence genes in multidrug-resistant Escherichia coli isolates from humans, animals, and the environment: One health perspective.

Escherichia coli is one of the critical One Health pathogens due to its vast array of virulence and antimicrobial resistance genes. This study used multiplex PCR to determine the occurrence of virulence genes bfp, ompA, traT, eaeA, and stx1 among 50 multidrug-resistant (MDR) E. coli isolates from humans (n = 15), animals (n = 29), and the environment (n = 6) in Dar es Salaam, Tanzania.

Development of a multi-epitope chimeric vaccine in silico against Babesia bovis, Theileria annulata, and Anaplasma marginale using computational biology tools and reverse vaccinology approach.

The three rickettsial parasites- Babesia bovis, Theileria annulata and Anaplasma Marginale are responsible for causing Babesiosis, Theileriosis and Anaplasmosis among cattle. These diseases exist due to spreading of infected ticks. A large number of cattle were found to suffer from mixed infections caused by the three parasites at the same time.

Computational design of multi-epitope vaccine against Hepatitis C Virus infection using immunoinformatics techniques.

Hepatitis C Virus (HCV) is a blood borne pathogen that affects around 200 million individuals worldwide. Immunizations against the Hepatitis C Virus are intended to enhance T-cell responses and have been identified as a crucial component of successful antiviral therapy. Nevertheless, attempts to mediate clinically relevant anti-HCV activity in people have mainly failed, despite the vaccines present satisfactory progress.

Exploring effector protein dynamics and natural fungicidal potential in rice blast pathogen Magnaporthe oryzae.

Rice blast, caused by Magnaporthe oryzae, is one of the most destructive fungal diseases in rice, resulting in major economic losses worldwide. Genetic and genomic studies have identified key genes and proteins, such as AvrPik variants and MAX proteins, that are crucial for the pathogen's virulence. These effector proteins interact with specific alleles of the Pik gene family on rice chromosome 11, modulating the host's immune response.

Heterogeneous and multiple conformational transition pathways between pseudoknots of the SARS-CoV-2 frameshift element.

Frameshifting is an essential mechanism employed by many viruses including coronaviruses to produce viral proteins from a compact RNA genome. It is facilitated by specific RNA folds in the frameshift element (FSE), which has emerged as an important therapeutic target. For SARS-CoV-2, a specific 3-stem pseudoknot has been identified to stimulate frameshifting.

Macromolecular interactions and geometrical confinement determine the 3D diffusion of ribosome-sized particles in live cells.

The crowded bacterial cytoplasm is composed of biomolecules that span several orders of magnitude in size and electrical charge. This complexity has been proposed as the source of the rich spatial organization and apparent anomalous diffusion of intracellular components, although this has not been tested directly. Here, we use biplane microscopy to track the 3D motion of self-assembled bacterial genetically encoded multimeric nanoparticles (bGEMs) with tunable size (20 to 50 nm) and charge (-3,240 to +2,700 e) in live cells.