Search Results (16,206)

Urinary tract infections (UTIs) are a global health concern, with over 150 million cases annually, primarily caused by Escherichia coli. Due to anatomical differences, females, especially children and postmenopausal women, are four times more susceptible. Crucially, E. coli has developed widespread antimicrobial resistance (AMR), including resistance to broad-spectrum agents and the emergence of Extended-Spectrum Beta-Lactamase (ESBL)-producing strains. This retrospective study analyzed hospital records from 95 female patients with positive urine cultures at Siblin Governmental Hospital in 2024. Patients were stratified into three age categories: children (≤18 years), adults (18–64 years) and elderly patients (>64 years). Statistical analysis using SPSS focused on descriptive resistance patterns and differences across age groups. Overall, cephalothin (85.7%) and cefaclor (78.49%) exhibited the highest resistance rates. Conversely, tigecycline (97.22%) and ertapenem (91.67%) showed the highest susceptibility. Resistance patterns varied significantly by age. For instance, elderly patients showed high resistance to agents like Augmentin (52.5%) and cefixime (66.1%), while the pediatric group (≤18 years) displayed exceptionally high resistance to cefixime (90.0%). E. coli isolates show high resistance to conventionally used antibiotics, complicating UTI treatment. These findings highlight the need for continuous local surveillance, particularly focusing on third-generation cephalosporins and beta-lactamase production. Ultimately, age is a critical factor that must be considered when determining empirical antibiotic therapy for UTIs. Full article

Potato virus Y (PVY) is a major threat to global potato production, causing yield losses of nearly 90%. This emphasizes the urgent need to explore the genetic factors underlying resistance mechanisms. Developments in transcriptomics and plant genomes have shed significant light on the genetic underpinnings of PVY resistance. This review summarizes current knowledge on PVY biology and structure, its impacts, key hypersensitive resistance (HR) and extreme resistance (ER) genes and their associated molecular markers, genomic strategies for discovering resistance genes and improving resistance breeding, and challenges. Genetic resistance is a key strategy for controlling PVY, primarily through HR and ER, which are governed by specific genes: the Ny gene for HR and the Ry gene for ER. Our understanding of the molecular mechanisms underlying this resistance has increased significantly due to the advancement of high-throughput sequencing methods, including RNA and whole-genome sequencing. More than 10 PVY resistance genes have been identified in potato, including well-characterized ER genes such as Ry_sto, Ry-f_sto, Ry_adg, Ry_chc, and Ry(o)_phu, as well as HR genes such as Ny-1, Ny-2, and Ny-Smira, which are discussed in this review. Transcriptomic analyses have revealed the involvement of small RNAs and other regulatory molecules in modulating resistance responses. Transcriptomic studies have also identified 6071 differentially expressed genes (DEGs) in potato cultivars infected with PVY, highlighting strong defense responses influenced by strain, cultivar, and environmental conditions. The identification of these resistance genes facilitates the development of PVY-resistant cultivars through marker-assisted selection and gene pyramiding, offering significant opportunities to enhance PVY management and promote sustainable potato production under the challenges posed by climate change. Full article

Human herpesvirus 6 (HHV-6) is a common virus that can reactivate in immunocompromised patients, including lung transplant (LT) recipients. This study aimed to evaluate the clinical and functional implications of HHV-6 infection in LT patients through a retrospective analysis of 175 individuals who underwent lung transplantation at the City of Health and Sciences of Turin between 2014 and 2023. Surveillance bronchoscopies—including bronchoalveolar lavage (BAL) and transbronchial biopsies—were performed at scheduled intervals over a two-year period to detect HHV-6 and other pathogens, and to assess acute rejection. Spirometries were performed to evaluate graft function. Among the cohort, 33% of 822 BAL samples tested were positive for HHV-6, with a notable association between high viral load (≥500 copies/mL) and the development of post-transplant lymphoproliferative disorder (PTLD) (13% vs. 1%, p = 0.02) at 1 month and (9% vs. 1%, p = 0.026) at 12 months. Co-infection with CMV (78% in positives vs. 55% in negatives; p = 0.006), Epstein–Barr virus (EBV) (35% vs. 16%; p = 0.010), and bacterial and fungal infection (specifically, a higher rate of isolation of Achromobacter xylosoxidans (13%), p = 0.010) was frequently observed in conjunction with HHV-6 positivity. Notably, patients with at least one HHV-6 positive BAL exhibited a significant reduction in forced vital capacity (FVC) at multiple follow-up points, FVC 82% in positives vs. 92% in negatives (p = 0.038) at 4 months and 87% vs. 98% p = 0.033 at 8 months and 87% vs. 99% p = 0.038 at 24 months. No direct associations with acute rejection or overall survival were found. By means of this study, we provide a wide overview of HHV-6 in lung transplant recipients, filling in a gap of evidence in the field. We report a remarkable incidence and a significant association with acknowledged clinically relevant viral infections, PTLD, and functional tests decline, with no association with mortality. Full article

Bovine viral diarrhea virus (BVDV) is a major pathogen responsible for significant economic losses in the global cattle industry. The diverse transmission routes and the characteristics of asymptomatic infections make it difficult to contain the spread; there is an urgent need to develop new effective antiviral strategies. Nanobodies (Nbs) have become a promising new type of antiviral agent due to their advantages, including small molecular size, stable structure, high specificity, and ease of production. This study successfully screened a specific nanobody, Nb7, targeting the key functional protein NS5A of BVDV using phage display technology. Furthermore, the nanobody was effectively delivered into Madin–Darby bovine kidney (MDBK) cells by fusing it with the cell-penetrating peptide TAT. The results demonstrate that TAT-Nb7, specifically targeting the non-structural protein NS5A of BVDV, significantly inhibits viral replication in MDBK cells. In conclusion, this study indicates that TAT-Nb7 holds promise as a therapeutic candidate for the prevention and control of BVDV infection. Full article

The Influenza A Virus (IAV) is known to hijack cellular proteins during its replication. IAV infection increases the expression of Heat-shock-protein family A (Hsp70) member 5 (HSPA5) in human cells, but its specific function in the viral life cycle remains unclear. This study aims to elucidate the function of HSPA5 in IAV replication, by implementing HSPA5 knockdown (KD) in A549 cells and assessing its impact on IAV’s viral protein translation, genomic RNA transcription, and the host cellular proteome. HSPA5 KD significantly reduced progeny virus release, although viral RNA levels were unaffected. Interestingly, levels of viral structural proteins increased in HSPA5 KD cells after infection. Treatment with HSPA5 inhibitor also suppressed IAV replication, confirming its role as a host dependency factor. Proteomic profiling revealed 116 proteins altered in wild-type cells and 223 in HSPA5 KD cells, with 32 uniquely dysregulated in wild-type and 139 unique to HSPA5 KD cells. In HSPA5 knockdown cells, the altered proteins were linked to pathways such as EIF2, EGF, PEDF, CNTF, IL-13, and G-protein receptor signaling, as well as to cellular processes like lymphocyte activation and regulation of immune and blood cell death, which were not affected in wild-type cells after IAV infection. Overall, this study suggests that HSPA5 contributes to late stages of IAV replication, likely assembly or maturation, and represents a promising target for antiviral drug development. Full article

Equine herpesvirus (EHV) infections represent a significant global veterinary and economic challenge affecting both horses and donkeys across all inhabited continents. This narrative review comprehensively examines the nine distinct EHV species (EHV-1 through EHV-9), their taxonomic classification within Alphaherpesvirinae and Gammaherpesvirinae subfamilies, and their diverse host tropism patterns. The complex molecular pathogenesis involves sophisticated viral glycoproteins (gK, gB, gC, gH, gM, gL, gG, gD, gI, gE) that orchestrate cellular invasion, immune evasion, and intercellular transmission. Clinical manifestations vary considerably, ranging from respiratory diseases and reproductive failures to severe neurological disorders, with EHV-1 demonstrating the most severe presentations including myeloencephalopathy. Global distribution analysis reveals widespread circulation across Europe, Asia, Africa, the Americas, and Oceania, with species-specific clinical patterns. Current therapeutic options remain largely supportive, with experimental compounds like berbamine and cepharanthine, celastrol, blebbistatin, and hyperoside showing promise in preclinical studies. Vaccination programs demonstrate limited effectiveness, failing to prevent transmission at population levels despite inducing individual immune responses. The sophisticated immune evasion strategies employed by EHVs, including the “Trojan horse” mechanism utilizing infected leukocytes, highlight the complexity of host–pathogen interactions and underscore the urgent need for innovative prevention and treatment strategies. Full article

Background: After the implementations of Highly Active Antiretroviral Therapy (HAART) HIV infection became a chronic condition and the clinical focus on non-AIDS-related comorbidities such as hypertension and chronic kidney disease has increased. This study aims to investigate the prevalence and independent predictors of hypertension and albuminuria in a cohort of people with HIV (PWHIV) with high rates of viral suppression. Methods: This is a cross-sectional study of 183 HAART-experienced PWHIV. Hypertension, defined as office systolic blood pressure of ≥140 mmHg or diastolic blood pressure of ≥90 mmHg and albuminuria, was defined as a sex-based albumin–creatinine ratio (ACR) of >355 mg/g for females and >250 mg/g for males. Univariable and multivariable logistic regression was conducted to identify the association of hypertension and albuminuria with demographic, clinical, and HIV-specific factors. Results: The prevalence of hypertension was 43.9% (n = 74) and albuminuria was 22.4% (n = 41). In the multivariable analysis, factors independently associated with prevalence of HTN were older age, overweight/obesity, and diabetes mellitus. TDF-based ART was explored as a potential factor but did not reach statistical significance (aRR = 1.85, p = 0.065). For albuminuria, older age, diabetes mellitus, and duration of HAART (aRR = 1.03 per year) were revealed as independent predictors. Conclusions: The results of this study demonstrate that the development of hypertension is primarily driven by traditional metabolic risk factors. However, the progression to albuminuria appears to be influenced not only by these comorbidities but also by long-term HIV disease and HAART exposure. These findings underline the critical need for the screening and management of hypertension and other comorbidities to mitigate the risk of long-term cardiovascular and renal complications in this aging population of PWHIV. Full article

Leishmaniasis and Chagas disease, caused by Leishmania spp. and Trypanosoma cruzi, are neglected tropical diseases with significant global health burden, particularly in resource-limited regions. Despite their impact, diagnosis and treatment remain challenging due to limited diagnostic tools and the toxicity of available therapies. Our objective is to propose the incorporation of markers for the diagnosis of leishmaniasis and Chagas disease using ncRNA. This narrative review evaluates studies published between 2010 and 2024 (PubMed, Scopus, Google Scholar) using the SANRA scale to assess the potential of non-coding RNAs (ncRNAs) as biomarkers for these infections. Both parasites release small RNAs via extracellular vesicles that modulate host–pathogen interactions and gene expression. Although RNA interference machinery is absent in T. cruzi and most Leishmania species, it persists in early-diverging lineages. In leishmaniasis, distinct miRNA expression profiles—including miR-155-5p, miR-5011-5p, miR-6785-5p, and miR-361-3p—demonstrate high diagnostic accuracy for detecting infection (AUC up to 1.0). Serum long ncRNAs such as MALAT1 and NUTM2A-AS1 show potential diagnostic value, though clinical validation remains pending. For Chagas disease, the available evidence on ncRNAs primarily addresses the diagnosis of clinical manifestations rather than initial infection. Host miRNAs, including miR-21, miR-145, miR-146a/b, and miR-19a-3p, correlate with cardiac involvement, immune dysregulation, and inflammation during chronic T. cruzi infection. Circulating miRNAs exhibit modest sensitivity (57–67%) and specificity (57–80%) for diagnosing chronic Chagas cardiomyopathy, indicating their utility in assessing disease progression and organ damage rather than detecting early infection. This review distinguishes between ncRNAs that diagnose infection and those that evaluate disease severity or organ involvement. Altered ncRNA expression profiles represent promising biomarkers for species differentiation, treatment monitoring, and assessing cardiac complications in Chagas disease, with broader diagnostic applications emerging for leishmaniasis. Full article

Background: Urinary tract infections (UTIs) are the most common infections among kidney transplant recipients, with prevalence rates ranging from 12% to 75% in studies from North America and Australia and from 4.5% to 85% in the Middle East. These infections can significantly impact graft survival and patient quality of life, increasing the risk of hospitalization, morbidity, and mortality. Escherichia coli is the leading cause of UTIs in transplant patients, but multidrug-resistant (MDR) pathogens are a growing concern, especially in Saudi Arabia. Several factors, including advanced age, female gender, and use of urinary catheters, contribute to post-transplant UTIs. This study focuses on the Saudi population, aiming to assess the prevalence, risk factors, and treatment strategies for recurrent and multidrug-resistant UTIs in kidney transplant recipients. Methods: This retrospective cohort study reviewed the medical records of kidney transplant patients at King Faisal Specialist Hospital & Research Center, Jeddah, in addition to data from King Fahad Hospital, Madinah, Saudi Arabia, between March and May 2022. Adult patients (≥18 years) who developed recurrent UTIs within two years post-transplant were included, while those with one or no UTI episode or incomplete records were excluded. Results: Seventy-five of 491 screened patients (15.3%) experienced recurrent UTIs, contributing to a total of 219 episodes. Klebsiella pneumoniae was the most frequent pathogen, isolated in 94 episodes (42.9%). Key risk factors for recurrence included complicated UTIs (OR = 4.60, p = 0.005), multidrug-resistant organisms (MDROs) (OR = 3.14, p = 0.021), and ureteric stents (OR = 4.07, p = 0.042). Carbapenems were primarily used for complicated UTIs, while cephalosporins and penicillins were used for uncomplicated infections. A significant post-UTI rise in serum creatinine was observed (p < 0.001). Conclusions: Recurrent UTIs predominantly caused by K. pneumoniae are common in kidney transplant recipients, particularly in patients over 45, with multidrug-resistant organisms, or with ureteric stents. While a direct causal link to graft loss was not established, these infections can lead to increased creatinine levels, hospitalizations, and healthcare costs and increased carbapenem use. These findings highlight the critical need for institution-specific antimicrobial stewardship programs focused on infection prevention and optimized antibiotic use to improve outcomes in this vulnerable population. Full article

Background: Inflammation is a common reason for dogs to present to veterinary clinics. Early diagnosis of systemic inflammation is important. Acute phase proteins, like C-reactive protein, are useful but not specific to infection. In human medicine, the intensive care infection score (ICIS) offers a faster, cost-effective alternative using advanced hematological parameters. While ICIS is not available for veterinary use, some components (e.g., neutrophil side fluorescent light) can be measured using analyzers like the Sysmex XN-1000V. Objectives: This study aimed to establish a control group of healthy dogs for the novel parameters neutrophil side fluorescent light (NE-SFL), neutrophil side scattered light (NE-SSC), and neutrophil forward scattered light (NE-FSC) and assess their utility in detecting inflammation in diseases such as sepsis, pyometra, steroid-responsive meningitis-arteritis (SRMA), and idiopathic epilepsy. Methods & Results: Value ranges were calculated based on 21 healthy dogs. Compared to controls, NE-SFL levels were significantly elevated in sepsis, pyometra, and SRMA, while NE-SSC was only elevated in sepsis and pyometra and NE-FSC only in sepsis. No increases were observed in idiopathic epilepsy. Manual gating of the white blood cell differential scattergram was necessary in samples showing high neutrophil toxicity and the presence of bands. Conclusion: NE-SFL and NE-SSC, obtainable from routine complete blood count, may serve as novel, accessible markers for inflammation in dogs. Further research is needed to validate their broader diagnostic use. Full article

Background: Escherichia coli (E. coli) bacteremia is a significant cause of mortality, particularly in older adults. Limited data exists on clinical outcomes in octogenarians. This study aims to evaluate the clinical outcomes of E. coli bacteremia in octogenarians and determine whether appropriate empirical therapy leads to improved outcomes in this specific population. Methods: We conducted a retrospective cohort study of hospitalized patients with E. coli bacteremia at Beilinson Hospital from January 2012 to December 2022. Clinical characteristics, bacteremia sources, antibiotic resistance patterns, and patient outcomes were analyzed. The primary outcome was 30-day mortality. Multivariate regression was used to assess the impact of empirical antibiotic appropriateness on mortality. Results: The study included 2717 patients, of which 1042 (38%) were 80 years or older. Older patients had more comorbidities with increased rates of ischemic heart disease (20% vs. 14%, p < 0.01) and congestive heart failure (19% vs. 9%, p < 0.01). Patients with 3rd generation cephalosporin resistant strains were more likely to receive inappropriate empiric antibiotic therapy (54% vs. 23%, p < 0.01). Although appropriate empirical therapy was associated with improved survival in univariate analysis (19% vs. 28%, p < 0.01), it was not an independent predictor of 30-day mortality in multivariate analysis [adjusted OR = 1.10, 95% CI (0.64–1.81), p = 0.7]. A lower SOFA score [adjusted OR = 0.17, CI95% (0.01–0.31), p < 0.01] was associated with decreased 30-day mortality. Hypoalbuminemia was significantly associated with increased 30-day mortality [adjusted OR = 2.49, CI95% (0.1.56–3.97), p < 0.01]. Conclusions: E. coli bacteremia in octogenarians is associated with significant mortality. While timely appropriate antibiotic therapy is crucial, mortality appears to be more influenced by overall health status, comorbidities, and infection severity. Future research should focus on addressing these factors and developing personalized care strategies to improve survival in this high-risk group. Full article

Nature has long served as a prolific source of bioactive compounds, offering structurally diverse scaffolds for the development of therapeutics. In recent years, increasing attention has been given to nature-inspired covalent inhibitors, molecules that form covalent bonds with pathogen- or cancer-specific targets, due to their potential selectivity and sustained biological activity. This review explores the landscape of covalent inhibitors derived from natural sources, with a focus on compounds from fungi, marine organisms, bacteria and plants. In particular, emphasis is placed on the molecular mechanisms through which these compounds exert their activity against different types of pathogens and other biomedically relevant targets, highlighting key structural motifs that facilitate covalent interactions. Furthermore, the review discusses recent advances in synthetic modification, target identification, and optimization strategies that bridge natural compound discovery with modern drug development. By drawing insights from nature’s chemical repertoire, this work ultimately displays the potential of natural covalent inhibitors as a promising foundation for next-generation anti-infective and anticancer therapeutics. Full article

Citrus leaf blotch virus (CLBV) is a positive-sense single-stranded RNA virus belonging to the genus Citrivirus within the family Betaflexiviridae. It infects a broad range of economically significant fruit crops, including citrus, kiwifruit, and apple. Surveys conducted in the field have documented appreciable incidence rates in several hosts, thereby emphasizing its emerging threat to global pomiculture. Comprehensive surveillance of CLBV genetic diversity is indispensable for predicting strain-specific epidemics and designing durable, broadly protective control strategies. Current surveys of CLBV diversity are still gene-fragment-centric, with whole-genome resolution remaining largely untapped. In this study, an analysis of codon usage bias analysis was performed using all available CLBV full-length genomes. The findings revealed that CLBV exhibits low codon usage bias, with natural selection, rather than mutational drift, being the primary driver. Phylogenetic analysis has been demonstrated to categorize isolates according to their host of origin rather than their geographical location. This observation suggests that host adaptation may supersede spatial structure in CLBV evolution and reinforce natural selection as the dominant force shaping its codon usage landscape. From the perspective of the codon adaptation index, Prunus avium is the host that exerts the greatest influence on the formation of its codon usage bias. The present study provides the first genome-wide portrait of CLBV codon usage bias, offering a robust framework for future investigations into its origin and evolutionary dynamics. Full article

(1) Background: Diabetic retinopathy (DR), caused by hypo- and hyperglycaemia, is the leading cause of blindness. Hypoglycemia induces endoplasmic reticulum stress and retinal cell death in mice, and low-glucose conditions induce macroautophagy/autophagy defects in 661W photoreceptor cells and retinal explants. Very few studies have analyzed the effect of hypoglycemia on retinal autophagy, so we decided to fill this gap. (2) Methods: We use C57BL/6 and GFP-LC3 mice and isolated retinal ganglion cells (RGCs) from both mouse models to study the autophagy process. (3) Results: Intraocular injection of rapamycin and 5 h hypoglycemia showed an increase in autophagosomes formation, specifically in the RGCs. Isolated GFP-LC3 RGCs showed an increase in autophagosome formation under low-glucose conditions. In contrast, infection of isolated C57BL/6 RGCs with the RFP-GFP-LC3 lentivirus revealed a defect in autophagosome/lysosome fusion under these conditions. (4) Conclusions: This study showed that 5 h hypoglycemia induces autophagosomes formation in mouse RGCs; however, a defect in the fusion process inhibits the protective effect of autophagy. Therefore, modulating both autophagic and apoptotic pathways might be important to avoid complications associated with DR. Full article

Mpox, caused by monkeypox virus (MPXV), remains a Public Health Emergency of International Concern (PHEIC) and poses a serious global health threat. Current therapeutic options for MPXV infection are limited. The orthopoxvirus dual-specificity phosphatase H1 plays critical roles in suppressing interferon signaling, regulating early viral transcription, and modulating viral core protease activity. Suppressing H1 expression markedly reduces the production of infectious viral particles, highlighting it as a promising antiviral target. Here, we developed a high-throughput enzymatic assay using p-nitrophenyl phosphate as a substrate to discover MPXV H1 inhibitors. We demonstrated that both the N-terminal helix α1, which mediates H1 dimerization, and the catalytic residue Cys110 are indispensable for enzymatic activity, validating them as potential “hot spots” for drug design. Screening identified 17 potent inhibitors with nanomolar IC₅₀ values and minimal cytotoxicity. Molecular docking revealed that these inhibitors bind within the active site of MPXV H1, interacting with residues in the P-loop and WPD-loop, thereby restricting substrate access and suppressing activity. This study identifies several potent inhibitors of MPXV H1, establishing a foundation for the development of novel antivirals against MPXV infection. Full article