Search Results (1,362)

Capsular polysaccharides are critical virulence factors of Klebsiella pneumoniae, enabling the bacterium to evade host immune recognition and exacerbate infection. Phage-derived depolymerases, which specifically degrade these capsular polysaccharides, are increasingly recognized as a highly promising strategy for the treatment of bacterial infections. In the present study, we isolated and characterized a lytic Klebsiella pneumoniae phage, named phiTH1, and sequenced its genome. The K30-type capsular polysaccharide was identified as the receptor for phiTH1 infection. A tail fiber protein with a pectate lyase domain, Dop5, was then recognized as a potential K30-type depolymerase. Therefore, the recombinant protein Dop5 was expressed in Escherichia coli and purified, and its in vitro capsular depolymerase activity was demonstrated. Further, by using a murine aspiration pneumonia model induced by K30-type Klebsiella pneumoniae TH1, we found that Dop5 protected 80% of mice from lethal challenge with Klebsiella pneumoniae. After Dop5 treatment, the pathological damage in multiple organs of mice was alleviated, the bacterial load was reduced, and serum levels of inflammatory cytokines and complement C3 decreased, along with a significant reduction in the pathological score of the lungs. Hence, this study revealed the potential of the depolymerase Dop5 for the treatment of Klebsiella pneumoniae infections. Full article

This study reports the biosynthesis of selenium nanoparticles (Se-NPs) using four newly isolated strains of lactic acid bacteria, molecularly identified as Lactiplantibacillus pentosus, Lactiplantibacillus plantarum, Lactiplantibacillus plantarum, and Lactobacillus acidophilus. The synthesized Se-NPs were characterized using Transmission Electron Microscopy (TEM), Energy Dispersive X-ray Spectroscopy (EDX), Fourier Transform Infrared Spectroscopy (FTIR), and UV-Vis Spectroscopy, and zeta potential analysis. The result revealed that their size ranged from 16 nm to 90 nm with favorable stability and purity. The Se-NPs exhibited significant antimicrobial and antibiofilm activities against certain Gram-positive, Gram-negative bacteria, and Candida albicans, particularly those produced by isolate S4, which showed the lowest MIC values and highest biofilm inhibition. Furthermore, MTT assays revealed selective cytotoxicity against the A549 cancerous lung cell line, with minimal toxicity toward normal Wi38 cells. These findings suggest that biosynthesized Se-NPs are a promising, biocompatible candidate for combating antibiotic-resistant pathogens and biofilm-associated infections. Full article

Bronchopulmonary dysplasia (BPD) is a significant complication of hyperoxia in preterm neonates. Extracellular vesicle (EV)-based therapies derived from mesenchymal stem cells (MSCs) show regenerative potential. We investigated the therapeutic efficacy of EVs derived from human umbilical cord mesenchymal stem cells (HUCMSCs), particularly those engineered to overexpress miR-7704 in a hyperoxia-induced BPD cell model. EVs were isolated from GFP- and miR-7704-transfected HUCMSCs. A549 alveolar epithelial cells were exposed to normoxic or hyperoxic conditions and treated with HUCMSC-EV or miR-7704-HUCMSC-EV. EV uptake was confirmed using fluorescence microscopy. Cell proliferation was evaluated, and apoptosis was assessed by means of Western blot analysis of caspase family proteins and apoptosis-related markers. Both HUCMSC-EV and miR-7704-HUCMSC-EV enhanced A549 cell proliferation under hyperoxic stress, with miR-7704-HUCMSC-EV showing greater efficacy. Protein-level analyses revealed hyperoxia-induced increases in cleaved caspase-3, caspase-7, and FasL, along with decreased Bcl-2. Treatment with miR-7704-HUCMSC-EV significantly reversed these effects, whereas HUCMSC-EVs minimally impacted apoptotic protein expression. Bioinformatic analysis predicted that hsa-miR-7704 targeted the 3′ UTR of APOPT1. miR-7704-HUCMSC EVs also enhanced the expression of key antioxidant enzymes, including SOD1, SOD2, and HO-1. miR-7704-enriched HUCMSC-derived EV significantly promoted cell survival and mitigated hyperoxia-induced apoptosis and oxidation in a BPD cell model, suggesting their potential therapeutic role in neonatal lung injury. Full article

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a global health challenge, partly due to the prolonged duration and toxicity of standard antibiotic regimens. Adjunctive therapies that enhance antimicrobial efficacy and modulate host immunity are urgently needed. Curcumin, a natural bioactive compound derived from Curcuma longa, possesses broad therapeutic properties, including anti-inflammatory, antioxidant, antibacterial, and antiviral effects. This study evaluated the effects of curcumin in combination with first- and second-line antibiotics against Mtb in both in vitro and in vivo models. Our results demonstrated that curcumin exerts direct antibacterial activity against both the drug-sensitive H37Rv strain and a multidrug-resistant (MDR) clinical isolate. Furthermore, curcumin synergized with conventional antibiotics, enhancing bacterial clearance in infected macrophages while promoting the production of IL-12, a key cytokine in protective immune responses. In a murine model of progressive pulmonary TB, combination therapy with curcumin and first-line antibiotics significantly reduced the lung bacterial burden and improved behavioral outcomes compared to antibiotic treatment alone. These findings suggest that curcumin acts through both direct antimicrobial mechanisms and immune modulation, supporting its potential as an adjunctive therapy agent for TB. Future studies should focus on optimizing curcumin formulation, dosing, and bioavailability to facilitate the clinical translation of this compound. Full article

Avian viral arthritis (AVA), caused by avian reovirus (ARV), is a viral disease in chickens that has led to significant economic losses in the poultry industry. Recent studies have shown that traditional ARV vaccines based on the S1133 strain fail to protect against emerging ARV variants. In this study, we isolated and characterized three ARV strains (G4, YV, WF) from immunized chicken flocks with respiratory and arthritic symptoms. Genomic analysis revealed that the σC genes of G4, YV, and WF shared only 55.5%, 55.7%, and 58.7% sequence homology, respectively, with the S1133 strain. Phylogenetic analysis placed them in different branches, indicating they are variant strains. YV and WF belong to genotype III, and G4 falls into genotype VI. Whole genome analysis revealed gene segment reassortment among the variants. Pathogenicity testing in three-week-old SPF chickens showed that G4 (genotype VI) caused swelling of footpads, whereas WF (genotype III) did not. G4-infected chickens exhibited significantly higher viral loads in the thymus, lungs, spleen, and bursa of Fabricius than those in the WF-infected chickens, indicating viruses from different genotypes showed various pathogenesis. These results suggested an urgent need for new updates of vaccines against the variant ARVs, especially the genotype VI virus. Full article

Ethnopharmacological relevance: Glehnia littoralis (GL) is a well-known traditional Chinese medicine used to clear the lungs and benefit the stomach. Glehnia littoralis polysaccharides (GLPs) constitute one of the primary active ingredients of GL, demonstrating notable biological activities including immunomodulatory, antioxidant activity, and antitumor effects. Aim of the study: This review aims to provide the latest and the most comprehensive information on GLPs, specifically investigating their extraction technologies, isolation and purification methods, structural characteristics, and pharmacological activities of GLPs. It seeks to lay a foundation for further investigating pharmacological activities and application scope and guide the safe clinical practice of GLPs. Materials and methods: PubMed, Google Scholar, Web of Science, Elsevier, China National Knowledge Infrastructure (CNKI), and other online databases were used to collect literature about extraction, isolation, and purification methods, structural characteristics, and pharmacological activities of GLPs published before January 2025. Results: Polysaccharides are the main active ingredient of GL. Currently, 19 types of GLPs have been extracted. Methods of extracting GL include hot water extraction, ultrasound-assisted extraction, and enzyme extraction. The most frequently used method of separation and purification within GLP is column chromatography, often entailing cellulose column chromatography and ion exchange chromatography. GLPs have various pharmacological activities, including immunomodulatory, antioxidant, and antitumor. Conclusions: While GLPs show promising immunomodulatory and antitumor effects, elucidating their structure–activity relationships is essential for advancing our understanding and requires future research. Full article

Background/objectives: Cellular senescence is a hallmark of aging that contributes to tissue dysfunction and age-related diseases. This process is characterized by the activation of the cyclin-dependent kinase inhibitor p16^INK4A and the secretion of pro-inflammatory factors collectively known as the senescence-associated secretory phenotype (SASP). In this study, we used human lung-derived cells, including A549 and IMR90 fibroblasts, to identify bioactive compounds from the roots of Liquidambar formosana that suppress p16^INK4A activity and attenuate SASP expression. Methods: Bioactivity-guided isolation was performed to obtain target compounds. The structures of the new compounds were elucidated using extensive 1D and 2D NMR spectroscopic analyses as well as high-resolution mass spectrometry. All isolated compounds were evaluated for their ability to inhibit p16^INK4A, a key regulator of the cell cycle and an important tumor suppressor protein. Results: Two previously undescribed monoterpenoids (1 and 2), characterized as cinnamic acid esters with a monoterpene-derived core, were isolated from the roots of L. formosana, along with six known compounds (3–8). Notably, compound 3 exhibited promising inhibition of p16^INK4A with an IC₅₀ value of 3.9 μM. Furthermore, this compound attenuated the senescence phenotype, as demonstrated by β-galactosidase staining and RT-qPCR analysis. This represents the first report identifying bioactive monoterpenoids from L. formosana that inhibit aging-related biomarkers such as p16^INK4A. Conclusions: These results suggest that cinnamic acid-conjugated monoterpenoids may serve as interesting lead structures for the development of agents targeting the p16^INK4A pathway for the treatment of aging-associated diseases. Further studies will be required to clarify the mechanisms of action of this compound and to evaluate its in vivo efficacy. Full article

Polyporusterone B, a triterpene carboxylic acid isolated from Polyporus umbellatus Fries, exhibits anti-cancer and anti-hemolytic activities; however, its anti-inflammatory properties and underlying mechanisms remain unelucidated. We studied the anti-inflammatory effects of Polyporusterone B using lipopolysaccharide (LPS)-stimulated Raw264.7 murine macrophages (in vitro) and LPS-induced endotoxin shock in C57BL/6 mice (in vivo). Results showed that Polyporusterone B (1, 5, and 10 μM) had no cytotoxicity toward Raw264.7 cells, but significantly inhibited LPS-induced production of nitric oxide (NO) and pro-inflammatory cytokines (tumor necrosis factor (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6)) in a concentration- and time-dependent manner, as demonstrated by Griess assay, qPCR, and ELISA. Western blot analysis revealed that Polyporusterone B suppressed LPS-induced phosphorylation of mitogen-activated protein kinases (ERK, P38, and NK) and reduced phosphorylation-mediated degradation of inhibitor of κBα (IκBα). Immunofluorescence and immunohistochemical staining further confirmed that Polyporusterone B blocked nuclear translocation of nuclear factor kappa-B (NF-κB)/Rel A in both Raw264.7 cells and mouse tissues. In the in vivo model, Polyporusterone B pretreatment significantly mitigated LPS-induced multi-organ pathological damage (e.g., lung edema, hepatic inflammation, renal hemorrhage) and downregulated tissue levels of TNF-α, IL-1β, and IL-6. These findings suggest that Polyporusterone B exerts anti-inflammatory effects by inhibiting the mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways, suggesting its potential as a therapeutic candidate for inflammatory diseases. Full article

Background: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy. Complete tumor resection (R0) is critical for prognosis and may require multivisceral resection in locally advanced cases. However, data on outcomes after multivisceral resection for ACC remain limited. This study evaluates the perioperative and oncologic outcomes of patients undergoing multivisceral resection for suspected ACC. Methods: We retrospectively analyzed 21 patients who underwent multivisceral resection with curative intent for suspected ACC. Three were later diagnosed with other tumor entities (sarcoma, non-small cell lung carcinoma metastasis and ganglioneuroma). The remaining 18 patients with histologically confirmed ACC were compared with 19 patients who underwent isolated adrenalectomy during the same study period. Results: Patients undergoing multivisceral resection were significantly younger (p = 0.003), had larger (p < 0.001) and more advanced tumors according to ENSAT classification (p < 0.001). All but one had open surgery; laparoscopic or hybrid approaches were more common in the isolated adrenalectomy group. Multivisceral resections were associated with longer operative times (p = 0.002), all required an ICU admission (p < 0.001), and had longer hospital stays (p = 0.001). Lymphnode metastases were observed only in the multivisceral group (p = 0.002). No significant differences were found in complication rates (p = 0.081), resection status (p = 0.091), progression-free survival (p = 0.095), or overall survival (p = 0.71). Conclusions: Multivisceral resection is a safe and feasible approach in specialized centers and may achieve comparable oncologic outcomes to isolated adrenalectomy, even in patients with more advanced disease. It should be considered when R0 resection is required and technically achievable. Full article

In May 2025, a female giraffe in poor body condition died unexpectedly at a zoo in Henan Province, China. A bacterial strain, designated HN-1, was isolated from the heart, liver, spleen, lungs, and kidneys of the deceased animal. After 24 h of incubation at 37 °C on Luria–Bertani (LB) agar, the colonies appeared round, smooth, pale yellow, translucent, and raised. Gram staining revealed that the isolate was a Gram-positive, rod-shaped, and non-spore-forming bacterium. Based on 16S rRNA gene sequencing, the strain showed more than 99.7% homology with reference sequences of E. mexicanum from various sources in GenBank. The results of the susceptibility test showed that E. mexicanum was susceptible to levofloxacin, clindamycin, chloramphenicol, trimethoprim, rifampicin, tetracycline, minocycline, gentamicin, erythromycin, and doxycycline, but resistant to oxacillin, penicillin, ciprofloxacin, and linezolid. These findings provide valuable insights for the diagnosis and treatment of infections caused by E. mexicanum in giraffes. Full article

Background: Infections are common complications in patients with non-small cell lung cancer (NSCLC) and may adversely influence clinical outcomes. Their prognostic impact after definitive treatment is not well established. This study aimed to investigate the incidence, microbiological profile, and prognostic significance of infections occurring within one year after definitive treatment in patients with NSCLC. Methods: We retrospectively analyzed patients with NSCLC who completed definitive treatment between 1 January 2016, and 31 December 2023. Microbiological culture results obtained within one-year post-treatment and inflammatory markers measured one month after treatment were evaluated. Pathogens were classified as healthcare-associated infection (HAI) or non-HAI agents. Overall survival (OS) was estimated using the Kaplan–Meier method, and prognostic factors were assessed using Cox regression analysis. Results: Among 214 eligible patients, 45 had positive microbiological cultures. Gram-negative bacteria predominated (n = 24), with Pseudomonas aeruginosa (n = 8) and Acinetobacter baumannii (n = 6) being the most frequently isolated species. Among all isolates, 20 Gram-negative and 6 Gram-positive microorganisms were identified as HAI pathogens. In multivariate analysis, culture positivity (HR: 2.75, p < 0.001) remained an independent prognostic factor for worse OS. Conclusion: Infections within the first year after definitive treatment, particularly those caused by HAI-related Gram-negative pathogens, are associated with reduced OS in NSCLC. Early microbiological diagnosis, targeted antimicrobial therapy, and strict infection prevention strategies may help improve outcomes in this high-risk population. Full article

Background: The detection of circulating tumor cells (CTCs) holds significant promise for the diagnosis and monitoring of lung cancer (LC). However, the clinical utility of CTCs is limited by the heterogeneity of their phenotypes and the shortcomings of existing detection methods, which often rely on epithelial markers like EpCAM. DNA aptamers offer a promising alternative due to their high affinity, stability, and ability to recognize diverse cancer-specific biomarkers. Methods: This study utilized DNA aptamers LC-17 and LC-18, previously selected against primary lung tumor tissue, to isolate and detect CTCs in the peripheral blood of 43 non-small cell lung cancer (NSCLC) patients. Mass spectrometry (LC-MS/MS) was employed to identify the target proteins of aptamer LC-17. CTCs from patients’ blood and healthy donors were isolated via filtration after erythrocyte and lymphocyte lysis and stained with FAM-labeled LC-17 and LC-18 aptamers for detection using fluorescence and light microscopy. Results: Mass spectrometry identified neutrophil defensin 1 (DEFA1) and peroxiredoxin-2 (PRDX2) as the primary protein targets of aptamer LC-17 in CTCs, both of which were absent in healthy donor samples. CTC enumeration revealed statistically significant correlations between elevated CTC counts (>3 cells/4 mL blood) and advanced primary tumor size (T4 vs. T1–T3, p = 0.012), extensive regional lymph node metastasis (N3 vs. N1–N2, p = 0.014), and shorter overall survival (median 24 vs. 32 months, p < 0.05). Conclusions: The developed aptamer-based liquid biopsy method effectively captures heterogeneous CTC populations independent of EpCAM expression. The strong correlation of CTC counts with disease progression and survival underscores their clinical relevance as a prognostic biomarker in NSCLC. This approach presents a viable, non-invasive tool for disease monitoring and stratification of NSCLC patients, with potential for integration into clinical practice. Full article

Selenium (Se) is a trace mineral with antioxidant and anti-inflammatory properties. Se deficiency increases oxidative stress and immunosuppression. In swine, dietary Se supplementation enhances immunity and growth, and previous studies suggest it protects immune cells during viral infection. Porcine reproductive and respiratory syndrome virus (PRRSV) causes severe respiratory and reproductive failure in swine, resulting in annual losses of 1.2 billion USD. Vaccine efficacy is hampered by the virus’s high mutation rate, requiring alternative approaches. This study examines the effects of organic (DL-Selenomethionine, L-Selenomethionine, yeast-selenium) and inorganic (sodium selenite) Se on PRRSV infection in vitro. Porcine alveolar macrophages, the primary target of PRRSV in the lung, were isolated from healthy animals and infected with PRRSV-2 with or without Se. Mitochondrial function, gene expression, oxidative stress, and viral load were assessed post-infection. DL-selenomethionine showed increased glycolytic and mitochondrial ATP production relative to other compounds, suggesting improved mitochondrial function. No antiviral activity against PRRSV was observed. Transcriptome analysis revealed infection-driven modulation, with upregulation of IL6, IL8, IL1B1, MX1, and TXNRD1, but Se had no significant effect. While Se did not exhibit antiviral activity in vitro, its enhancement of mitochondrial function offers additional insight supporting its potential immunomodulatory benefits observed in previous in vivo studies. Full article

Mixed infections of Mannheimia haemolytica and Mycoplasma bovis are relatively common in bovine respiratory diseases, presenting severe respiratory symptoms and high mortality that severely endanger the cattle industry. In this study, a serotype A1 strain of Mannheimia haemolytica, designated as XJCJMh1, was isolated and identified from the lung tissue of a hybrid Simmental calf infected with Mycoplasma bovis. The pathogenicity of this strain was evaluated using Kunming mice as a model. The results indicated that infection with XJCJMh1 caused pathological manifestations such as pulmonary hemorrhage and edema in mice. Subsequently, the genome of this strain was sequenced and assembled using Illumina sequencing to obtain general genomic features. The genome was annotated and analyzed for gene functions using the Swiss-Prot, NR, GO, COG, KEGG, CAZy, TCDB, and Pfam databases. Additionally, the virulence factors and resistance genes of this strain were annotated using the PHI, VFDB, and CARD databases. The genome of Mannheimia haemolytica XJCJMh1 is 2,595,489 base pairs (bp) in length, with a GC content of 40.93%. Notably, this strain exhibits three distinct genomic islands and contains 98 effectors associated with the type III secretion system (T3SS). The XJCJMh1 strain harbors 74 virulence genes and 45 resistance genes. We annotated the proteins, genes, and associated GO and KEGG pathways of the XJCJMh1 strain; exploring the relationship between these annotations and the strain’s pathogenicity is of considerable value. This study is of great significance for clarifying the pathogenic mechanism and genetic characteristics of the Mannheimia haemolytica strain XJCJMh1 in cattle, and its results provide a scientific reference for analyzing the genomic basis of pathogenicity and drug resistance of Mannheimia haemolytica under co-infection conditions. Full article

Extracellular vesicles (EVs) are rapidly gaining recognition as critical mediators of inter-cellular communication during viral infections. To contribute to fill the gap in knowledge regarding the role of EVs in adenovirus infection, we used human adenovirus type 4 of species Mastadenovirus exoticum (HAdV-E4), a prevalent respiratory and ocular pathogen, and characterized the cargo and biological properties of EVs released by HAdV-E4-infected A549 lung epithelial cells at a pre-lytic stage of infection. Using immunocapture-based isolation and multi-omics approaches, we found that infection profoundly alters the EV uploaded proteome and small non-coding RNA repertoire. Mass spectrometry identified 268 proteins unique to EVs purified from infected cells (AdV-EVs), with enrichment in pathways supporting vesicle trafficking and viral protein translation, and importantly also a few virus-encoded proteins. A small RNA transcriptome analysis showed differential uploading in AdV-EVs of various small non-coding RNAs, including snoRNAs, as well as the presence of virus associated RNAs I and II. Notably, AdV-EVs contained viral genomic DNA and could initiate productive infection upon delivery to naïve cells in the absence of detectable viral particles. Our data suggest that EVs released during the HAdV-E4 infection may serve as vehicles for non-lytic viral dissemination and highlight their possible role in intra-host dissemination Full article