Search Results (2,841)

Mpox, caused by the Mpox virus (MPXV), emerged globally in 2022 with the Clade IIb strain, presenting a critical public health challenge. While MPXV is primarily characterized by fever and rash, gastrointestinal (GI) complications, such as diarrhea and proctitis, have also been observed. This study is a reanalysis of GSE219036 without own data and focuses on the impact of MPXV infection on the colon, using human-induced pluripotent stem cell-derived colon organoids as a model. We applied a tailored statistical framework for RNA-seq data, Generalized Linear Models with Quasi-Likelihood F-tests and Relaxed Magnitude–Altitude Scoring (GLMQL-RMAS), to identify differentially expressed genes (DEGs) across MPXV clades: MPXV I (Zr-599 Congo Basin), MPXV IIa (Liberia), and MPXV IIb (2022 MPXV). Through a novel methodology called Cross-RMAS, we ranked genes by integrating statistical significance and biological relevance across all clades. Machine learning analysis using the genes identified by Cross-RMAS, demonstrated 100% accuracy in differentiating between the different MPXV strains and mock samples. Furthermore, our findings reveal that MPXV Clade I induces the most extensive alterations in gene expression, with significant upregulation of stress response genes, such as HSPA6 and FOS, and downregulation of genes involved in cytoskeletal organization and vesicular trafficking, such as PSAP and CFL1. In contrast, Clade IIb shows the least impact on gene expression. Through Gene Ontology (GO) analysis, we identified pathways involved in protein folding, immune response, and epithelial integrity that are disrupted in infected cells, suggesting mechanisms by which MPXV may contribute to GI symptoms. Full article

Methotrexate (MTX) is an anti-folate chemotherapeutic agent that is considered to be a gold standard in Acute Lymphoblastic Leukemia (ALL) therapy. Nevertheless, toxicities induced mainly due to high doses of MTX are still a challenge for clinical practice. MTX pharmacogenetics implicate various genes as predictors of MTX toxicity, especially those that participate in MTX intake like solute carrier family 19 member 1 (SLC19A1). The aim of the present study was to evaluate the association between SLC19A1 polymorphisms and its regulatory miRNAs with MTX toxicity in children with ALL. A total of 86 children with ALL were included in this study and were all genotyped for rs2838958, rs1051266 and rs1131596 SLC19A1 polymorphisms as well as the rs56292801 polymorphism of miR-5189. Patients were followed up (48, 72 and 96 h) after treatment with MTX in order to evaluate the presence of MTX-associated adverse events. Our results indicate that there is a statistically significant correlation between the rs1131596 SLC19A1 polymorphism and the development of MTX-induced hepatotoxicity (p = 0.03), but there is no significant association between any of the studied polymorphisms and mucositis or other side effects, such as nausea, emesis, diarrhea, neutropenia, skin rash and infections. In addition, when genotype TT of rs1131596 and genotype AA of rs56292801 are both present in a patient then there is a higher risk of developing severe hepatotoxicity (p = 0.0104). Full article

Background: The activation of the growth hormone receptor (GHR) is a major determinant of body growth. Defective GHR signaling, as seen in human Laron dwarfism, resulted in low plasma IGF-1 concentrations and limited growth, but also marked absence in the development of breast cancer and type 2 diabetes. In vitro, we identified a small molecule (C#1) that inhibits the translation of GHR mRNA to receptor protein. Methods: Before its application in humans as a potential anticancer drug, C#1 was tested in animals to evaluate whether it could be administered to achieve a plasma concentration in vivo that inhibits cell proliferation in vitro without causing unwanted toxicity. To evaluate the efficacy and toxicity of C#1, a group of six intact female Beagle dogs was treated daily each morning for 90 days with an oral solution of C#1 in Soiae oleum emulgatum at a dose of 0.1 mg/kg body weight. During treatment, dogs were closely monitored clinically, and blood samples were taken to measure plasma C#1 concentrations, complete blood counts (CBC), clinical chemistry, and endocrinology. At the end of the treatment, dogs were euthanized for gross and histopathological analysis. An additional group of six female Beagle dogs was included for statistical reasons and only evaluated for efficacy during treatment for 30 days. Results: Daily administration of C#1 resulted in a constant mean plasma concentration of approximately 50 nmol/L. In both groups, two out of six dogs developed decreased appetite and food refusal after 4–5 weeks, and occasionally diarrhea. No significant effects in CBC or routine clinical chemistry were seen. Plasma IGF-1 concentrations, used as biomarkers for defective GHR signaling, significantly decreased by 31% over time. As plasma growth hormone (GH) concentrations decreased by 51% as well, no proof of GHR dysfunction could be established. The measured 43% decrease in plasma acylated/non-acylated ghrelin ratios will also lower plasma GH concentrations by reducing activation of the GH secretagogue receptor (GHSR). C#1 did not directly inhibit the GHSR in vivo, as shown in vitro. There were no significant effects on glucose, lipid, or folate/homocysteine metabolism. Conclusions: It is concluded that with daily dosing of 0.1 mg C#1/kg body weight, the induction of toxic effects prevented further increases in dosage. Due to the concomitant decrease in both IGF-1 and GH, in vivo inhibition of GHR could not be confirmed. Since the concept of specific inhibition of GHR synthesis by small molecules remains a promising strategy, searching for compounds similar to C#1 with lower toxicity should be worthwhile. Full article

Getah virus (GETV) is a mosquito-borne virus belonging to the genus Alphavirus in the family Togaviridae. Its infection poses an increasing threat to animals and public health in China. In this study, an epidemiological survey of GETV on 46 pig farms in Jiangxi Province, China, was performed; GETV isolation and characterization were carried out, including a complete sequence determination and phylogenetic analysis; and pathogenicity of the GETV was experimentally investigated by inoculating newborn piglets with the isolated GETV strain. Epidemiological studies conducted on the organs of infected pigs, aborted piglets, and the blood of aborted sows sampled from pig farms in Jiangxi Province, China, demonstrated that 44 out of the 46 pig farms were positive for GETV, which is a positivity rate of 95.65% (44/46). Of the 411 samples tested, 47.93% (197/411) were found positive for GETV. A GETV strain called GETV-JX-CHN-22 was obtained, which showed stable proliferation in Vero cells. One-step growth curve results showed that the GETV-JX-CHN-22-P7 (passage 7) isolate reached a peak titer of 10^8.3 TCID₅₀/mL at 24 hpi. An analysis of the whole-genome sequencing results showed that GETV-JX-CHN-22 (prototype) and GETV-JX-CHN-22-P7 shared nucleotide sequence similarities of 95.3% to 99.6% with 73 reference strains of GETV in GenBank. Genetic evolution analysis revealed that GETV-JX-CHN-22 and GETV-JX-CHN-22-P7 belonged to the GIII group, the same group members of most strains were reported in China. Animal inoculation experiments indicated that piglets exhibited typical symptoms and pathological changes of GETV infection after 24 h inoculation, which reproduced the pathogenicity of GETV field strain infections in piglets. To our knowledge, this study is the first report on the detection and isolation of porcine GETV associated with diarrhea from pig farms in Jiangxi Province, China. It is of great importance to study the infection spectrum, transmission mechanism, and public health significance of GETV. The results provide foundations for the genomic and biological (pathogenic) characteristics of the circulating GETV in Jiangxi Province, China. Full article

During the growth process of weaned piglets, digestive problems such as gastrointestinal disorders and diarrhea are common. Farmers usually use antibiotics to help piglets grow smoothly. However, the overuse of antibiotics can lead to antibiotic resistance issues. Therefore, this study chose to use plant extracts as feed additives to explore their potential as alternatives to antibiotics. Additionally, Tilmicosin was used as the antibiotic because it is widely used in treating respiratory infections in piglets. Since traditional Chinese medicine often uses natural products, we selected Guizhi Li-Zhong (GLZ) extract as an alternative to antibiotics. The experiment involved 126 piglets, each 4 weeks old, which were randomly assigned to one of four groups: the sham group (basal diet without supplements, 10.3 ± 0.4 kg, n = 31), the low-dose GLZ group (basal diet with 0.05% GLZ, 10.9 ± 0.4 kg, n = 32), the regular-dose GLZ group (basal diet with 0.2% GLZ, 10.6 ± 0.4 kg, n = 32), and the regular-dose Tilmicosin antibiotic group (basal diet with 0.2% Tilmicosin, 10.2 ± 0.3 kg, n = 31). We recorded and compared the survival rate, growth rate, feed conversion ratio, and diarrhea incidence among four groups of weaned piglets from the 4th to the 10th weeks of age. Then, we examined the oxidative stress, inflammation, and apoptosis in small intestine tissue (jejunum and ileum) through immunohistochemistry and Western blot and compared the gut microbiota in large intestine tissue (colon and rectum) through a next-generation sequencing (NGS) analysis. Our results showed that weaned piglets supplemented with 0.05% and 0.2% GLZ had better survival rates, growth rates (p < 0.01), and feed conversion ratios (p < 0.01) compared to those receiving sham treatment. Even weaned piglets supplemented with 0.2% GLZ performed better than those supplemented with 0.2% Tilmicosin antibiotics (p < 0.05). Furthermore, the incidence of diarrhea and small intestine injury (indicated by oxidative stress-, inflammation-, and apoptosis-related proteins) in piglets supplemented with 0.05% and 0.2% GLZ was lower than in piglets receiving sham treatment (p < 0.05). Even piglets supplemented with 0.2% GLZ had less injury than those supplemented with 0.2% Tilmicosin antibiotics (p < 0.05). The NGS results further showed that GLZ treatment significantly improved beneficial bacteria in weaned piglets (p < 0.05), while antibiotic treatment reduced beneficial bacteria (p < 0.05). In summary, we recommend adding GLZ to the feed as an alternative to antibiotics. This not only effectively reduces intestinal damage but also improves the gut microbiota, thereby promoting the growth of weaning piglets. Full article

Bovine respiratory disease (BRD) is a significant global health issue in cattle farming, leading to substantial economic losses. This study analyzed the microbiological profiles of BRD outbreaks in nine dairy cattle herds in southern Brazil. We examined 36 biological samples, including 24 deep nasopharyngeal swabs (NS) and 12 lung tissue, from 29 suckling and 7 weaned heifer calves with acute BRD. PCR and RT-PCR techniques were used to partially amplify the genes of five viruses and four respiratory bacteria. A total of 8 different microorganisms, 4 viruses (bovine viral diarrhea virus, n = 5; bovine coronavirus, n = 3; bovine alphaherpesvirus 1, n = 3; and bovine parainfluenza virus 3, n = 2), and 4 bacteria (Pasteurella multocida, n = 16; Mycoplasma bovis, n = 8; Histophilus somni, n = 7; and Mannheimia haemolytica, n = 4) were identified in 29 (80.5%) samples. Seven samples (four lung tissue and three NS) were negative for all the microorganisms. Mixed infections were more common (62.1%) than single infections (37.9%). Bacterial nucleic acids were more commonly co-detected in NS than in lung tissue. Nucleic acids from a single pathogen were more frequently detected in lung tissues than in NS. M. bovis was the only bacterium detected in the lower respiratory tract. Understanding the microbiological profiles of the respiratory tracts of dairy calves with clinical signs of BRD is crucial for implementing effective biosecurity measures to prevent BRD in suckling and weaned dairy heifer calves. Full article

This study evaluated the antibacterial efficacy of 700 feline-derived lactic acid bacteria (LAB) strains against enteropathogenic Escherichia coli (EPEC), a common cause of diarrhea in cats. Following comprehensive screening, strains ZY25 and ZY35 were identified as the most effective, with inhibition zones of ≥22 mm. These strains demonstrated strong tolerance against stress conditions, such as low pH, bile salts, and gastrointestinal fluids, alongside high hydrophobicity and auto-aggregation abilities. Safety evaluations confirmed the absence of hemolytic activity, virulence factors, and antibiotic resistance genes. The antibacterial activity of these strains is attributed to the production of organic acids, particularly lactic acid and acetic acid. These findings suggest that strains ZY25 and ZY35 have potential as natural and effective probiotic treatments for managing EPEC-induced diarrhea in cats, thus offering an alternative to conventional antibiotics. Full article

Porcine epidemic diarrhea (PED) is an acute, highly contagious, and infectious disease caused by porcine epidemic diarrhea virus (PEDV). PEDV can affect pigs of all ages, with 50~100% mortality in neonatal piglets and substantial economic losses in the swine industry. In the present study, 347 fecal and intestinal samples were collected from seven regions in China during 2020–2022. A comprehensive molecular investigation of the spike (S) gene of PEDV strains was carried out, which included phylogenetic analysis of the obtained PEDV sequences. Epidemiological surveillance data indicate that the GIIc subgroup strains are widely distributed among pigs. A PEDV strain was successfully isolated from positive small intestine samples and identified through RT-PCR detection using specific N gene primers of PEDV, indirect immunofluorescence assay (IFA), TEM analysis, genome sequencing, and full-length S gene analysis, named PEDV/SC/2022. RDP and SimPlot analysis showed that the isolate originated from the recombination of PEDV/AH2012 and PEDV/AJ1102. In conclusion, our findings contribute to the current understanding of PEDV epidemiology and provide valuable information for the control of PED outbreaks in China. Full article

Background: Inflammatory bowel disease (IBD) is associated with multiple factors that influence bone metabolism. This study aimed to compare the clinical manifestations and diagnostic parameters of patients with Crohn’s disease (CD) and ulcerative colitis (UC) at the time of diagnosis, as well as to assess their relationship with subsequent bone disorders. Methods: Blood tests (including calcium–phosphate metabolism) and fecal tests (including calprotectin) were performed in eighty children recently diagnosed with IBD. Additionally, the bone densitometry results were evaluated in 25 of them. Results: Diarrhea (p = 0.02) and bloody stools (p < 0.001) were more frequent in patients with UC, whereas fever was more common in patients with CD (p = 0.003). Laboratory tests revealed anemia in 62.5% (50/80) and thrombocytosis in 36.3% (29/80). Higher calprotectin levels in the feces were found in girls at the time of diagnosis (p = 0.02). Osteopenia was detected in almost half of the examined patients (12/25), and 20% (5/25) met the criteria for osteoporosis. Low calcium levels at diagnosis were correlated with subsequent bone disorders (p = 0.005). Insufficient levels of vitamin D were detected in 77.8% (56/80). Conclusions: Early disease detection and the appropriate monitoring of children with IBD may decrease the risk of serious consequences, including osteoporosis. Full article

Among the pathogens that cause infectious diarrhea in China, Shigella is the most prominent. Shigellosis affects both adults and children, particularly those in developing nations, with nearly 190 million annual cases and a third resulting in fatalities. The recently emerged CRISPR/Cas system has also been increasingly applied for the detection of different biological targets. The lateral flow assay (LFA) has the advantages of short detection time, simple operation, high sensitivity, and low cost, and it provides an ideal platform for on-site detection. In this study, a recombinase polymerase amplification–CRISPR/Cas12a–LFA test for Shigella flexneri was constructed. The established method had good specificity and sensitivity, and the qualitative accuracy of 32 tested strains reached 100%. The detection limit of genomic DNA reached 8.3 copies/μL. With the advantages of high accuracy and portability, this diagnostic apparatus represents a novel method of identification and detection of Shigella flexneri, particularly in settings that lack complex laboratory infrastructure. Full article

Porcine epidemic diarrhea virus (PEDV) infection causes severe diarrhea and high mortality in neonatal piglets. Pseudorabies causes acute and often fatal infections in young piglets, respiratory disorders in growing pigs, and reproductive failure in sows. In late 2011, pseudorabies virus (PRV) variants occurred in Bartha-K61-vaccine-immunized swine herds, resulting in economic losses to the global pig industry. Therefore, it is essential to develop a safe and effective vaccine against both PEDV and PRV infections. In this study, we constructed a recombinant virus rPRV-PEDV S1 expressing the major neutralizing epitope region (COE, SS2, and SS6) of the PEDV S1 protein by homologous recombination technology and CRISPR/Cas9 gene editing technology, and then evaluated its biological characteristics in vitro and immunogenicity in pigs. The recombinant virus rPRV-PEDV S1 had similar growth kinetics in vitro to the parental rPRV NY-gE⁻/gI⁻/TK⁻ strain, and was proven genetically stable in swine testicle (ST) cells and safe for piglets. PEDV S1-specific antibodies were detected in piglets immunized with rPRV-PEDV S1 on the 7th day post-immunization (dpi), and the antibody level increased rapidly at 14–21 dpi. Moreover, the immunized piglets receiving the recombinant virus exhibited alleviated clinical signs and reduced viral load compared to the unvaccinated group following a virulent PEDV HN2021 strain challenge. Also, piglets immunized with rPRV-PEDV S1 developed a PRV-specific humoral immune response and elicited complete protection against a lethal PRV NY challenge. These data indicate that the recombinant rPRV-PEDV S1 is a promising vaccine candidate strain for the prevention and control of PEDV and PRV infections. Full article

Traveler’s diarrhea (TD) is one of the most common travel-related health problems, largely interfering with planned activities and potentially contributing to antimicrobial resistance. This study aimed to characterize the knowledge about TD among pre-travel consultation users of one Portuguese travel clinic and determine the impact of the consultation on knowledge levels. Using a quasi-experimental, separate-sample pretest–posttest design, participants were randomly assigned to two groups: control/pre-consultation group (CG) or experimental/post-consultation group (EG). An anonymous self-administered questionnaire was used. A total of 470 participants were analyzed (227 CG; 243 EG). The EG/post-consultation group showed significant improvement in knowledge, with correct answers increasing from 63% to 75% (p < 0.001). However, knowledge gaps persisted: over 50% were unaware of TD’s self-limited nature, 30% did not recognize loperamide as a symptom reliever, and 36% believed all travelers should take antibiotics to prevent TD. The educational level and previous travel outside Europe influenced baseline knowledge; previous travel medicine consultations and information on TD improved knowledge in both groups and made it easier to acquire knowledge on the subject. Thus, a pre-travel consultation effectively increased travelers’ TD knowledge. However, post-consultation knowledge levels remained suboptimal, indicating the need for targeted interventions to increase travelers’ literacy and optimize pre-travel consultations. Full article

Zero-valent copper and silver metals (Ms) nanoparticles (NPs) supported on carboxymethylcellulose (CMC) were synthesized for treating Enterotoxigenic Escherichia coli fimbriae 4 (ETEC:F4), a major cause of diarrhea in post-weaned pigs. The antibacterial properties of Cu⁰/CMC and Ag⁰/CMC were assessed on infected porcine intestinal enterocyte IPEC-J2, an in vitro model mimicking the small intestine. The lower average particle size (218 nm) and polydispersity index [PDI]: 0.25) for Ag⁰/CMC, when compared with those of Cu⁰/CMC (367 nm and PDI 0.96), were explained by stronger Ag⁰/CMC interactions. The minimal inhibitory concentration (MIC) and half inhibitory concentration (IC₅₀) of Ag⁰/CMC were lower in both bacteria and IPEC-J2 cells than those of Cu⁰/CMC, confirming that silver nanoparticles are more bactericidal than copper counterparts. IPEC-J2, less sensitive in MNP/CMC treatment, was used to further investigate the infective process by ETEC:F4. The IC₅₀ of MNP/CMC increased significantly when infected IPEC-J2 cells and ETEC were co-treated, showing an inhibition of the cytotoxicity effect of ETEC:F4 infection and protection of treated IPEC-J2. Thus, it appears that metal insertion in CMC induces an inhibiting effect on ETEC:F4 growth and that MNP/CMC dispersion governs the enhancement of this effect. These results open promising prospects for metal-loaded biopolymers for preventing and treating swine diarrhea. Full article

Equine colitis is a devastating disease with a high mortality rate. Infectious pathogens associated with colitis in the adult horse include Clostridioides difficile, Clostridium perfringens, Salmonella spp., Neorickettsia risticii/findlaynesis, and equine coronavirus. Antimicrobial-associated colitis can be associated with the presence of infectious pathogens. Colitis can also be due to non-infectious causes, including non-steroidal anti-inflammatory drug administration, sand ingestion, and infiltrative bowel disease. Current treatments focus on symptomatic treatment (restoring fluid and electrolyte balance, preventing laminitis and sepsis). Intestinal epithelial ion channels are key regulators of electrolyte (especially sodium and chloride) and water movement into the lumen. Dysfunctional ion channels play a key role in the development of diarrhea. Infectious pathogens, including Salmonella spp. and C. difficile, have been shown to regulate ion channels in a variety of ways. In other species, there has been an increased interest in ion channel manipulation as an anti-diarrheal treatment. While targeting ion channels also represents a promising way to manage diarrhea associated with equine colitis, ion channels have not been well studied in the equine colon. This review provides an overview of what is known about colonic ion channels and their known or putative role in specific types of equine colitis due to various pathogens. Full article

Crohn’s disease (CD) is a chronic inflammatory bowel condition with increasing global incidence. Diagnosing CD is challenging and requires close collaboration between clinicians and pathologists due to the lack of specific diagnostic criteria. Histologically, CD is characterized by transmural inflammation, crypt distortion, metaplasia, and granulomas, although granulomas are not always present. Schaumann bodies (SB), initially described in sarcoidosis, are rare in CD but have been reported in about 10% of cases. This case report presents a 4-year-old female with chronic hemorrhagic diarrhea, severe anemia, and elevated inflammatory markers. Endoscopic and histological evaluations suggested CD, with the presence of SB in the gastric mucosa. Further investigations ruled out sarcoidosis, confirming a diagnosis of multi-segmental, very early onset CD with atypical histological features. SB are inclusions composed of calcium carbonate crystals and conchoid bodies, typically found within giant cells. The presence of SB in the mucosa is rare, limiting their diagnostic significance in endoscopic biopsies. Differential diagnosis should exclude other granulomatous diseases such as intestinal tuberculosis and sarcoidosis. This case highlights the importance of considering SB in the diagnosis of CD, particularly in pediatric patients. Full article