Enterococcus species are Gram-positive cocci normally found in the gut but have emerged as opportunistic pathogens in healthcare settings, with rising multidrug resistance, particularly vancomycin-resistant Enterococci (VRE) posing major therapeutic challenges. This study evaluated the antibacterial and synergistic effects of plant-derived stilbenes from Reynoutria japonica against clinical VRE isolates. Ten clinical Enterococcus faecalis isolates were identified using standard morphological, biochemical, and Gram-staining methods, and antibiotic susceptibility testing. The antibacterial activity of polydatin, resveratroloside, and trans-resveratrol was assessed by agar well diffusion, and evaluation of minimum inhibitory concentrations (MICs) and evaluation of bactericidal activity concentrations (MBCs), with synergistic effects tested in combination with vancomycin.Molecular docking was performed with DapF, vanA, and gelE proteins. All isolates were resistant to vancomycin, ampicillin, imipenem, gentamicin, and ciprofloxacin but sensitive to linezolid. All three stilbenes displayed antibacterial activity. Notably, trans-resveratrol was the most active compound, with a MIC value of 0.156 mM and bactericidal activity (an MBC value equal to the MIC). Furthermore, all compounds exhibited synergistic effects when combined with vancomycin. Phytochemical analysis confirmed these stilbenes as major constituents in the root extract of R. japonica. Molecular docking studies revealed strong binding affinities of the compounds to key virulence and resistance-associated proteins (DapF, VanA, and GelE). These results indicate that transresveratrol and related stilbenes are promising candidates for development as alternative or adjunct therapeutic agents against VRE infections. Additionally, this study substantiates the traditional use of R. japonica as a source of bioactive antimicrobial compounds.

Malignant melanoma is a neoplasm of melanin-producing cells predominantly of cutaneous origin, which uncommonly develops within gut mucosa. We present the case of a 58-year-old woman with complaints of abdominal pain, loss of appetite and weight.Esophagogastroduodenoscopy revealed a gastric mass and systemic imaging demonstrated widespread nodal and bilateral adrenal gland involvement. Histopathology of the gastric mass confirmed primary malignant mucosal melanoma of the stomach. The patient received three cycles of Nivolumab but did not respond, and thus, was then offered best supportive care. Although infrequent, mucosal melanoma can arise from the gastrointestinal tract, and in contrast to the cutaneous form, advanced disease usually has a dismal prognosis and responds poorly to immune checkpoint inhibitors. Primary gastric melanoma is an aggressive disease that is diagnosed by exclusion after the differential diagnosis of metastasis from a cutaneous or unknown primary site has been conducted. If available, patients with treatment-naïve mucosal melanoma should be considered for enrollment in clinical trials.

Tumor treatment remains a significant medical challenge,with many traditional therapies causing notable side effects.Recent research has led to the development of immunotherapy,which offers numerous advantages.Bacteria inherently possess motility,allowing them to preferentially colonize tumors and modulate the tumor immune microenvironment,thus influencing the efficacy of immuno-therapy.Bacterial outer membrane vesicles(OMVs)secreted by gram-negative bacteria are nanoscale lipid bilayer structures rich in bacterial antigens,pathogen-associated molecular patterns(PAMPs),various proteins,and vesicle structures.These features allow OMVs to stimulate immune system acti-vation,generate immune responses,and serve as efficient drug delivery vehicles.This dual capability enhances the effectiveness of immunotherapy combined with chemotherapy or phototherapy,thereby improving anticancer drug efficacy.Current research has concentrated on engineering OMVs to enhance production yield,minimize cytotoxicity,and improve the safety and efficacy of treatments.Consequently,OMVs hold great promise for applications in tumor immunotherapy,tumor vaccine development,and drug delivery.This article provides an overview of the structural composition and immune mechanisms of OMVs,details various OMVs modification strategies,and reviews the progress in using OMVs for tumor treatment and their anti-tumor mechanisms.Additionally,it discusses the challenges faced in translating OMV-based anti-tumor therapies into clinical practice,aiming to provide a comprehensive understanding of OMVs'potential for in-depth research and clinical application.

Tumor treatment remains a significant medical challenge, with many traditional therapies causing notable side effects. Recent research has led to the development of immunotherapy, which offers numerous advantages. Bacteria inherently possess motility, allowing them to preferentially colonize tumors and modulate the tumor immune microenvironment, thus influencing the efficacy of immunotherapy. Bacterial outer membrane vesicles (OMVs) secreted by gram-negative bacteria are nanoscale lipid bilayer structures rich in bacterial antigens, pathogen-associated molecular patterns (PAMPs), various proteins, and vesicle structures. These features allow OMVs to stimulate immune system activation, generate immune responses, and serve as efficient drug delivery vehicles. This dual capability enhances the effectiveness of immunotherapy combined with chemotherapy or phototherapy, thereby improving anticancer drug efficacy. Current research has concentrated on engineering OMVs to enhance production yield, minimize cytotoxicity, and improve the safety and efficacy of treatments. Consequently, OMVs hold great promise for applications in tumor immunotherapy, tumor vaccine development, and drug delivery. This article provides an overview of the structural composition and immune mechanisms of OMVs, details various OMVs modification strategies, and reviews the progress in using OMVs for tumor treatment and their anti-tumor mechanisms. Additionally, it discusses the challenges faced in translating OMV-based anti-tumor therapies into clinical practice, aiming to provide a comprehensive understanding of OMVs' potential for in-depth research and clinical application.

Appendicitis or Not Appendicitis: A Case Report of Acute Appendicitis Complicated with Disseminated MSSA and Iliopsoas Abscess This case report describes a 17-year-old female with acute appendicitis complicated by Methicillin-Sensitive Staphylococcus Aureus (MSSA) bacteremia and an iliopsoas abscess. Initially presenting with right iliac fossa pain and fever, she was diagnosed with acute appendicitis and underwent appendectomy. Postoperatively, she developed persistent fever and hip pain. Imaging revealed an abscess in the right iliacus muscle, which was drained percutaneously. MSSA was identified in the abscess culture. The patient recovered with targeted antibiotics. This case highlights the diagnostic challenges and importance of considering secondary infections in postoperative patients with atypical symptoms. Prompt recognition and treatment are essential for positive outcomes.

Human brucellosis is a neglected zoonotic problem worldwide with a high degree of morbidity in humans and is mostly overlooked due to other febrile conditions. The aim of this study was to evaluate the sero-prevalence and risk factors of human brucellosis among subjects living in Punjab, Pakistan. In this cross-sectional study, human blood samples were collected from seven districts of Punjab, Pakistan. Information regarding personal data, demographic data and potential risk factors was collected through a structured questionnaire. Detection of anti-Brucella antibodies was done through Rose Bengal Plate Test (RBPT) and Enzyme Linked Immunosorbent Assay (ELISA). Descriptive analysis, Chi square test and Odds ratio was applied using STATA software version 12. The sero-prevalence of human brucellosis was 13.13% with significantly higher percentage in males 17.23% and age group 25-40 years 16.50% (P=< 0.001). The demographic factors positively associated with human brucellosis were lack of education (P = 0.003; OR = 1.85) and farming as an occupation (P =<0.001; OR = 2.50) Similarly, among the risk factors studied, keeping animals at home (P =<0.001; OR = 2.03), slaughtering of animals (P =<0.001; OR = 15.87) and consuming raw milk (P =<0.001; OR = 5.42) were the factors strongly connected with human brucellosis. A massive awareness should be given to livestock farmers and individuals directly linked to animals regarding risk factors and transmission of brucellosis. Consumption of unpasteurized milk and its products should be condemned to curtail this neglected disease.

PURPOSE: The promoter methylation status of cell cycle regulatory genes plays a crucial role in the regulation of the eukaryotic cell cycle. CpG cytosines are actively subjected to methylation during tumorigenesis, resulting in gain/loss of function. E2F5 gene has growth repressive activities; various studies suggest its involvement in tumorigenesis. This study aims to investigate the epigenetic regulation of E2F5 in breast cancer to better understand tumor biology. METHODS: The promoter methylation status of 50 breast tumor tissues and adjacent normal control tissues was analyzed. mRNA expression was determined using SYBR® green quantitative polymerase chain reaction (PCR), and methylation-specific PCR was performed for bisulfite-modified genomic DNA using E2F5-specific primers to assess promoter methylation. Data was statistically analyzed. RESULTS: Significant (p<0.001) upregulation was observed in E2F5 expression among tumor tissues, relative to the control group. These samples were hypo-methylated at the E2F5 promoter region in the tumor tissues, compared to the control. Change in the methylation status (Δmeth) was significantly lower (p=0.022) in the tumor samples, indicating possible involvement in tumorigenesis. Patients at the postmenopausal stage showed higher methylation (75%) than those at the premenopausal stage (23.1%). Interestingly, methylation levels gradually increased from the early to the advanced stages of the disease (p<0.001), which suggests a putative role of E2F5 methylation in disease progression that can significantly modulate tumor biology at more advanced stage and at postmenopausal age (Pearson's r=0.99 and 0.86, respectively). Among tissues with different histological status, methylation frequency was higher in invasive lobular carcinoma (80.0%), followed by invasive ductal carcinoma (46.7%) and ductal carcinoma in situ (20.0%). CONCLUSION: Methylation is an important epigenetic factor that might be involved in the upregulation of E2F5 gene in tumor tissues, which can be used as a prognostic marker for breast cancer.
Biology ; Breast Neoplasms* ; Breast* ; Carcinogenesis ; Carcinoma, Ductal ; Carcinoma, Intraductal, Noninfiltrating ; Carcinoma, Lobular ; Cell Cycle ; Disease Progression ; DNA ; E2F5 Transcription Factor ; Epigenomics ; Eukaryotic Cells ; Genes, Regulator ; Humans ; Methylation* ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; RNA, Messenger ; Up-Regulation*

Toxoplasmosis is a protozoan disease that is caused by Toxoplasma gondii in livestock and humans. Due to its medical and veterinary importance, it is essential to study the seroprevalence of T. gondii infection among humans and animals in various parts of the world. The major objective of this study was to determine the seroprevalence and spatial distribution of toxoplasmosis in small ruminants (sheep and goats) of north-eastern region, Pakistan. A total of 1,000 animals comprising of sheep (n=470) and goats (n=530) were examined for T. gondii infection by using ELISA. An epidemiological data was collected in the form of questionnaire. A surface has been generated by using method of interpolation in Arc GIS with the help of IDW (inverse distance weight). The results showed higher seroprevalence of T. gondii in goats (42.8%) as compared to sheep (26.2%). The seroprevalence was higher in females as compared to males in all examined ruminants. Similarly, there is a wide variation in the seroprevalence of T. gondii in different breeds of sheep and goats showing higher seroprevalence in Teddy (52.8%) and Damani breed (34.5%) of goat and sheep's, respectively. The geographical and spatial distribution of T. gondii shows that it is widely distributed in different parts of the north-eastern region of Pakistan. Our results suggest widespread environmental contamination with T. gondii oocysts. It suggests us that small ruminants could be a potentially important source of T. gondii infection if their infected meat is consumed undercooked.
Animals ; Enzyme-Linked Immunosorbent Assay ; Female ; Goats* ; Humans ; Livestock ; Male ; Meat ; Methods ; Oocysts ; Pakistan* ; Ruminants ; Seroepidemiologic Studies* ; Sheep* ; Toxoplasma ; Toxoplasmosis*