Latest ArticlesPseudomonas aeruginosa is a widely distributed Gram-negative opportunistic pathogen that poses a serious threat to immunocompromised individuals, often leading to severe clinical infections. Sodium houttuyfonate (SH), the main active derivative of the Chinese medicinal herb Houttuynia cordata, has been widely used for anti-infection therapy. Recent studies suggest that the efficacy of SH against antibiotic-resistant pathogens extends beyond direct antibacterial effects to include delicate regulation of the host immune system. [Objective] To investigate the role of SH in promoting M1 polarization of alveolar macrophages against P. aeruginosa infection. [Methods] A mouse model of acute pneumonia caused by P. aeruginosa was established via intratracheal intubation. Hematoxylin and eosin (HE) staining was used to evaluate the histopathological changes in the lung tissue. Bacterial load in the lung tissue was determined by the plate counting method, and the expression of Toll-like receptor 4 (TLR-4) in the lung tissue was analyzed by immunohistochemistry (IHC). In the cell experiment, MH-S alveolar macrophages were co-cultured with SH for 6 h to induce M1 polarization. Polarization markers CD86 and CD206 were analyzed by immunofluorescence and flow cytometry, and phagocytic capacity was evaluated with P. aeruginosa at 1×105 CFU/mL. The mRNA levels and inflammation levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10) were measured by RT-qPCR and ELISA, respectively. The expression of proteins in the TLR-4/MyD88/NF-κB signaling pathway was analyzed by Western blotting. To decipher the mechanism, we constructed TLR-4 overexpression and knockdown cell models to confirm SH regulation of this pathway and related inflammatory factors via TLR-4. [Results] The in vivo experiment results indicated that SH significantly reduced P. aeruginosa proliferation in the mouse lung tissue. Both HE staining and IHC results demonstrated that pulmonary inflammation in the treatment group was alleviated compared with the model group, suggesting that SH may enhance host immune clearance and thereby mitigate acute pulmonary infection. The cell experiment showed that SH promoted early M1 polarization of MH-S cells and enhanced their phagocytosis of P. aeruginosa. Western blotting further confirmed activation of the TLR-4/MyD88/NF-κB pathway with upregulated protein expression after SH treatment. [Conclusion] SH can activate the TLR-4/MyD88/NF-κB pathway to induce M1 polarization of alveolar macrophages during early infection, thereby exerting significant phagocytic and anti-infective effects.
[Objective] To elucidate the primary bioactive component in Psoralea corylifolia seed extract that is responsible for inhibiting Pseudomonas amygdali pv. lachrymans (Pal) and to characterize its antibacterial mechanism. [Methods] The effect of isopsoralen on the growth curve of Pal and its minimum inhibitory concentration (MIC) were determined by the liquid culture assay. The antibacterial mechanism was investigated by transmission electron microscopy (TEM) combined with physiological and biochemical analyses. [Results] The MIC of isopsoralen against Pal was 400 mg/L. Isopsoralen disrupted the integrity of the bacterial cell wall and cell membrane, leading to leakage of intracellular contents. It interfered with cellular energy metabolism by inhibiting the activity of respiratory chain dehydrogenases. In addition, it impaired bacterial responses to environmental changes and colonization in the host by suppressing swarming motility, swimming motility, and biofilm formation. [Conclusion] Isopsoralen exerts its inhibitory activity against Pal through the synergistic actions of structural damage, energy disruption, and virulence suppression, ultimately abolishing the pathogen’s ability to infect the host. These findings provide a theoretical basis for the application of P. corylifolia seed extract as a botanical bactericide in the green management of cucumber bacterial angular leaf spot.
[Objective] To investigate the alleviating effects and mechanisms of Lacticaseibacillus paracasei CCFM1538 on inflammatory pain in mice. [Methods] A mouse model of inflammatory pain was induced by complete Freund’s adjuvant, and blank, model, dexamethasone, culture medium, fermentation supernatant, and high-dose/low-dose bacterial groups were set up. The ability of CCFM1538 to alleviate inflammatory pain was evaluated based on paw thickness, thermal/mechanical withdrawal threshold, HE staining of paw skin, inflammatory cytokines, glial cell immunofluorescence, and oxidative stress indicators. [Results] The fermentation supernatant of CCFM1538 significantly alleviated mouse paw swelling, increased the mechanical withdrawal threshold after modeling, reduced paw inflammatory cell infiltration, and decreased the expression of pro-inflammatory cytokines (IL-6 and CCL2). High-dose CCFM1538 cells significantly reduced the expression of pro-inflammatory cytokines (IL-1β and CCL2), decreased serum malondialdehyde levels, and inhibited abnormal activation of spinal cord glial cells. In addition, both significantly increased the thermal withdrawal threshold and serum superoxide dismutase activity in mice after modeling. [Conclusion] The fermentation supernatant and high-dose cells of CCFM1538 can alleviate inflammatory pain by reducing inflammation, alleviating oxidative stress, and regulating spinal glial cell activation. This study provides experimental evidence for the development of related functional foods.
Yeast β-glucan is a well-established immunomodulatory agent. Studies have demonstrated that compared with vegetative yeast cells, β-glucan exposed on the surface of mutant yeast spores exhibits enhanced immunostimulatory effects. [Objective] To screen and identify yeast mutants with enhanced ability to activate the mammalian immune system. [Methods] Two yeast mutants (osw1Δ and mum3Δ) exposing β-glucan on the spore wall were constructed, and their immunostimulatory activity was evaluated via the macrophage stimulation assay and a mouse model. The role of the Dectin-1 signaling pathway was verified through small interfering RNA-mediated gene knockdown experiments. [Results] The spore lysates of osw1Δ and mum3Δ induced the production of inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in macrophages. Their immune activation was mainly dependent on the Dectin-1-mediated signaling pathway. In vivo studies showed that after oral administration of the osw1Δ spore lysate, the levels of IL-6 and TNF-α in the mouse serum increased by 1.8-fold and 1.7-fold, respectively, compared with those after oral administration of the wild-type spore lysate. Moreover, the osw1Δ spore lysate exerted a significant tumor-suppressive effect. [Conclusion] The spores of osw1Δ exhibit strong immune-activating effects. This mutant could be a candidate for the development of novel immunomodulators.
[Objective] To investigate the effects of pea-oat mixed cropping at different ratios on soil nutrients, enzyme activities, and carbon-fixing microbial communities in the alpine region of Qinghai Province. [Methods] This study designed five treatments: monoculture of oat (T0), monoculture of pea (Q0), and pea-oat mixed cropping at three ratios (QT1, QT2, and QT3). Soil enzyme activities and physicochemical indicators were measured, and the community structure, diversity, and relationships with environmental factors of carbon-fixing bacteria were analyzed based on high-throughput sequencing data of cbbL. [Results] Compared with monoculture, mixed cropping significantly enhanced soil enzyme activities and nutrient content, with QT3 (the pea:oat ratio of 2:1) showing the most pronounced effects. Under QT3, the activities of sucrase, cellulase, protease, and other enzymes were the highest, and the content of soil organic carbon, total nitrogen, ammonium nitrogen, and other nutrients was also significantly increased. Mixed cropping optimized the community structure of soil carbon-fixing bacteria. Specifically, QT3 significantly increased the alpha diversity (with the highest Chao1 and Shannon indices) and enriched functional groups such as Cyanobacteria. Environmental factor analysis indicated that soil ammonium nitrogen, total nitrogen, and organic carbon were the main drivers of changes in the carbon-fixing bacterial community. Furthermore, microbial co-occurrence network analysis revealed that mixed cropping, especially QT3, significantly enhanced network complexity, connectivity, and modularity, which indicated higher structural stability and functional collaboration potential of the microbial community. [Conclusion] Pea-oat mixed cropping, particularly at a ratio of 2:1, significantly improved soil ecological functions in alpine regions by enhancing soil enzyme activities, increasing nutrient availability, and optimizing the structure and functional network of carbon-fixing microbial communities. This provides an effective approach for enhancing soil carbon sequestration potential and promoting sustainable agricultural development.
[Objective] To investigate the effects of diets with different concentrate to roughage ratios on the growth performance, rumen fermentation parameters, and serum metabolites of Yajiang snow cattle. [Methods] Twenty-seven healthy individuals of Yajiang snow cattle with similar body weights were selected and randomized into three groups (n=9). Cattle in the three groups were fed diets with the concentrate to roughage ratios being 40:60 (C40 group), 50:50 (C50 group), and 60:40 (C60 group). The pre-experimental period lasted for 7 days, and the experimental period lasted for 45 days. The growth performance, nutrient digestibility, volatile fatty acid content and microbiota structure in the rumen fluid, and serum metabolite content of the Yajiang snow cattle were measured. [Results] With the increase in the dietary concentrate to roughage ratio, the average daily gain and average daily feed intake of Yajiang snow cattle increased, while the apparent digestibility of crude protein and acid detergent fiber decreased (all P<0.05). As the dietary concentrate to roughage ratio increased, the pH value, acetate content, and acetate/propionate ratio in the rumen fluid decreased, whereas the propionate content increased (all P<0.05). Different concentrate to roughage ratios altered the microbiota structure in the rumen fluid of Yajiang snow cattle (P<0.05 or P<0.01). Specifically, the C60 group had lower relative abundance of Bacteroidota, Verrucomicrobia, Ruminococcus, Clostridium, Butyrivibrio, Pseudobutyrivibrio, and Bibersteinia but higher relative abundance of Bacillota, Prevotella, Succiniclasticum, and Selenomonas than the C40 group. Furthermore, different concentrate to roughage ratios changed the serum metabolite content of Yajiang snow cattle (P<0.05 or P<0.01). Specifically, the C40 group had significantly higher content of 5,6-dihydrouridine, 2-hydroxybutyric acid, and nitrilotriacetic acid but significantly lower content of 6-hydroxy-2-methylindole, N-acetylneuraminic acid, 2,6-dihydroxybenzoic acid, and taurodeoxycholic acid in the serum than the C50 and C60 groups. [Conclusion] Under the conditions of this experiment, different dietary concentrate to roughage ratios had significant effects on the production performance, rumen fermentation parameters, and serum metabolites of Yajiang snow cattle. Compared with the high roughage diet, the high concentrate diet significantly improved the production performance and promoted the rumen fermentation, while reducing the diversity of the rumen microbiota in Yajiang snow cattle.
[Objective] To investigate the efficacy of postbiotics prepared with Bifidobacterium animalis CCFM1155, a strain previously identified for its ability to enhance nuclear factor erythroid 2-related factor 2 (Nrf2) secretion in human immortalized epidermal cells, in alleviating skin aging. [Methods] A mouse model of skin aging was established by daily subcutaneous injection of D-galactose (500 mg/kg) for eight weeks (n=6 per group). The model mice were then orally administered either heat-inactivated cells (1155B) or concentrated fermentation supernatant (1155T) of CCFM1155 cells at a dose equivalent to 5×109 CFU of live bacteria. [Results] The 1155B was the primary postbiotic component exerting anti-skin aging effects, whereas the 1155T group showed no significant effect. Compared with the model group, the 1155B treatment ameliorated skin aging phenotypes by improving the skin tissue structure, increasing the epidermal thickness (P<0.05) and dermal collagen fiber density (P<0.01), and decreasing the expression of the senescence marker protein p21 and the activity of senescence-associated β-galactosidase (P<0.001). In addition, the 1155B treatment enhanced the antioxidant defense system of the skin by elevating the activities of total superoxide dismutase (P<0.05) and catalase (P<0.01), as well as the content of reduced glutathione (P<0.01), while lowering the malondialdehyde level (P<0.01). Mechanism studies revealed that the 1155B upregulated both the mRNA (P<0.05) and protein (P<0.001) levels of Nrf2 in the skin. Consequently, it promoted the transcription of key downstream antioxidant molecules, including heme oxygenase-1, peroxiredoxin, thioredoxin 1, and the glutamate-cysteine ligase catalytic subunit, thereby activating the downstream signaling pathway of Nrf2. [Conclusion] The inactivated cells of B. animalis CCFM1155 alleviates skin aging by activating the Nrf2 signaling pathway. These findings offer a novel perspective on postbiotic regulation of the Nrf2 pathway and lay a theoretical foundation for developing safe and effective anti-skin aging products.
Bovine mastitis is a key factor restricting the high-quality development of China’s dairy industry, while the prevalence of antimicrobial-resistant bacteria and recurrent infections have become severe challenges for the current prevention and control system. Although long-term antibiotic selection pressure may temporarily alleviate clinical symptoms, it significantly accelerates the evolution and dissemination of multidrug-resistant (MDR) pathogens, leading to rising treatment failure rates and a transition toward chronic disease. Epidemiological data indicate that the pathogen spectrum of bovine mastitis in China is dominated by Staphylococcus aureus, Streptococcus spp., and Enterobacteriaceae, with resistance genes propagating across species and regions through horizontal gene transfer (HGT) mediated by plasmids, transposons, and integrons. Furthermore, mechanisms such as biofilm formation, efflux pump activation, target modification, and intracellular escape interact with the mammary microenvironment to establish a robust defense barrier against host immune clearance and antimicrobial agents. Incorporating the principles of endogenous inflammation and metabolic dysregulation mediated by the “gut-mammary axis”, this paper systematically reviews the regional prevalence and molecular dissemination mechanisms of resistant pathogens in China. It provides an in-depth analysis of the pathological basis of recurrence and prospectively proposes comprehensive management strategies—ranging from precision diagnosis to alternative therapies—aiming to provide a theoretical foundation for the scientific control of bovine mastitis.
Neurodegenerative diseases, a group of highly prevalent central nervous system disorders, are closely linked to gut microbiota dysbiosis and impaired gut-brain axis function. The emerging gut-brain axis theory offers a novel perspective to explain how microbes exert remote, cross-organ regulation over the central nervous system. Recent studies have indicated that butyrate-producing bacteria, a core functional component of the gut microbiota, exhibit dynamic changes temporally and spatially correlated with the onset and progression of these diseases. These bacteria are thought to modulate the central nervous system microenvironment and disease pathology via the gut-brain axis. This article systematically reviews the bidirectional signaling mechanisms between the gut microbiota and the brain, analyzing the complex, multidimensional relationship between butyrate-producing bacteria and neurodegenerative diseases. This analysis encompasses population heterogeneity in patients with diverse clinical features and the dynamic evolution of these bacterial communities across different disease stages. We summarize the key mechanisms by which butyrate-producing bacteria regulate disease progression, including barrier protection, immunomodulation, metabolic regulation, and epigenetic modification. Furthermore, we explore their clinical potential as predictive biomarkers and therapeutic targets. We propose that future research should prioritize the development of targeted intervention strategies for gut-derived butyrate-producing bacteria. This review aims to provide a theoretical foundation and novel insights to advance both the fundamental investigation and clinical translation of these bacteria in the context of neurodegenerative diseases.
Coronavirus infections pose a serious threat to human health and have resulted in substantial economic losses to the livestock industry. Coronaviruses invade host cells primarily through two pathways: cell surface membrane fusion and endosomal membrane fusion. During viral entry, the spike protein subunit 1 (S1) recognizes and binds to cellular receptors, while the spike protein subunit 2 (S2) facilitates membrane fusion between the viral envelope and host cell membrane. Due to its high sequence conservation across different coronaviruses, S2 represents an attractive target for the development of broad-spectrum antiviral agents. Blocking S2-mediated membrane fusion can effectively inhibit viral infection. This review summarizes recent advances in understanding the mechanisms of coronavirus entry into host cells, the structure and function of the spike protein, and the development of membrane fusion inhibitors. In addition, this paper discusses the challenges and future prospects in targeting S2 for antiviral drug development, aiming to provide insights for coronavirus prevention and the discovery of novel antiviral therapeutics.