Skin microbiome profiling reveals the crucial role of microbial metabolites in anti-photoaging.

BACKGROUND: Skin microbiota is essential for health maintenance. Photoaging is the primary environmental factor that affects skin homeostasis, but whether it influences the skin microbiota remains unclear. OBJECTIVE: The objective of this study is to investigate the relationship between photoaging and skin microbiome. METHODS: A cohort of senior bus drivers was considered as a long-term unilateral ultraviolet (UV) irradiated population. 16S rRNA amplicon sequencing was conducted to assess skin microbial composition variations on different sides of their faces. The microbiome characteristics of the photoaged population were further examined by photoaging guinea pig models, and the correlations between microbial metabolites and aging-related cytokines were analyzed by high-throughput sequencing and reverse transcription polymerase chain reaction. RESULTS: Photoaging decreased the relative abundance of microorganisms including Georgenia and Thermobifida in human skin and downregulated the generation of skin microbe-derived antioxidative metabolites such as ectoin. In animal models, Lactobacillus and Streptobacillus abundance in both the epidermis and dermis dropped after UV irradiation, resulting in low levels of skin antioxidative molecules and leading to elevated expressions of the collagen degradation factors matrix metalloproteinase (MMP)-1 and MMP-2 and inflammatory factors such as interleukin (IL)-1ß and IL-6. CONCLUSIONS: Skin microbial characteristics have an impact in photoaging and the loss of microbe-derived antioxidative metabolites impairs skin cells and accelerates the aging process. Therefore, microbiome-based therapeutics may have potential in delaying skin aging.

Identification of the global regulatory roles of RraA via the integrative transcriptome and proteome in Vibrio alginolyticus.

Bacterial ribonuclease E (RNase E) is vital for posttranscriptional regulation by degrading and processing RNA. The RraA protein inhibits RNase E activity through protein-protein interactions, exerting a global regulatory effect on gene expression. However, the specific role of RraA remains unclear. In this study, we investigated rraA expression in Vibrio alginolyticus ZJ-T and identified three promoters responsible for its expression, resulting in transcripts with varying 5'-UTR lengths. During the stationary phase, rraA was significantly posttranscriptionally inhibited. Deletion of rraA had no impact on bacterial growth in rich medium Luria-Bertani broth with salt (LBS) but resulted in decreased biofilm formation and increased resistance to polymyxin B. Transcriptome analysis revealed 350 differentially expressed genes (DEGs) between the wild type and the rraA mutant, while proteome analysis identified 267 differentially expressed proteins (DEPs). Integrative analysis identified 55 genes common to both DEGs and DEPs, suggesting that RraA primarily affects gene expression at the posttranscriptional level. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis demonstrated that RraA facilitates the conversion of fatty acids, propionic acid, and branched-chain amino acids to acetyl-CoA while enhancing amino acid and peptide uptake. Notably, RraA positively regulates the expression of virulence-associated genes, including those involved in biofilm formation and the type VI secretion system. This study expands the understanding of the regulatory network of RraA through transcriptome analysis, emphasizing the importance of proteomic analysis in investigating posttranscriptional regulation.IMPORTANCERraA is an inhibitor protein of ribonuclease E that interacts with and suppresses its endonucleolytic activity, thereby playing a widespread regulatory role in the degradation and maturation of diverse mRNAs and noncoding small RNAs. However, the physiological functions and associated regulon of RraA in Vibrio alginolyticus have not been fully elucidated. Here, we report that RraA impacts virulence-associated physiological processes, namely, antibiotic resistance and biofilm formation, in V. alginolyticus. By conducting an integrative analysis of both the transcriptome and proteome, we revealed the involvement of RraA in carbon metabolism, amino acid catabolism, and transport, as well as in the type VI secretion system. Collectively, these findings elucidate the regulatory influence of RraA on multiple pathways associated with metabolism and pathogenesis in V. alginolyticus.

Gypenoside XLIX alleviates intestinal injury by inhibiting sepsis-induced inflammation, oxidative stress, apoptosis, and autophagy.

Intestinal barrier dysfunction is a significant complication induced by sepsis, yet therapeutic strategies targeting such dysfunction remain inadequate. This study investigates the protective effects of Gypenoside XLIX (Gyp XLIX) against intestinal damage induced by sepsis. Septic intestinal injury in mice was induced by cecum ligation and puncture (CLP) surgery. The biological activity and potential mechanisms of Gyp XLIX were explored through intraperitoneal injection of Gyp XLIX (40 mg/kg). The study demonstrates that Gyp XLIX improves the pathological structural damage of the intestine and increases tight junction protein expression as well as the number of cup cells. Through activation of the nuclear factor erythroid 2-related factor 2 - Kelch-like ECH-associated protein 1 (Nrf2-Keap1) pathway, Gyp XLIX enhances antioxidant enzyme levels while reducing the excessive accumulation of reactive oxygen species (ROS). In addition, Gyp XLIX effectively alleviates sepsis-induced intestinal inflammation by inhibiting the nuclear factor kappa B (NF-κB) pathway and activation of the NLRP3 inflammasome. Moreover, Gyp XLIX inhibits cell death through modifying phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, further enhancing its ability to shield the intestinal barrier. The combined action of these molecular mechanisms promotes the restoration of immune balance and reduces excessive autophagy activity induced under septic conditions. In summary, Gyp XLIX exhibits a significant preventive action against intestinal damage brought on by sepsis, with its mechanisms involving the improvement of intestinal barrier function, antioxidative stress, inhibition of inflammatory response, and cell apoptosis. This research offers a potential strategy for addressing intestinal barrier impairment brought on by sepsis.

Gypenoside XLIX Activates the Sirt1/Nrf2 Signaling Pathway to Inhibit NLRP3 Inflammasome Activation to Alleviate Septic Acute Lung Injury.

Currently, treatment options for acute lung injury (ALI) are limited. Gypenoside XLIX (Gyp-XLIX) is known for its anti-inflammatory properties, but there is a lack of extensive research on its effects against ALI. This study induced ALI in mice through cecal ligation and puncture surgery and investigated the biological activity and potential mechanisms of Gypenoside XLIX (40 mg/kg) by intraperitoneal injection. The in vitro ALI model was established using mouse lung epithelial (MLE-12) cells stimulated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP). Various methods, including Hematoxylin and Eosin (H&E) staining, biochemical assay kits, Quantitative Polymerase Chain Reaction (qPCR) analysis, Western blotting, Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) assay, immunofluorescence, and flow cytometry, were employed for this research. The results indicated that pretreatment with Gypenoside XLIX significantly alleviated pathological damage in mouse lung tissues and reduced the expression levels of inflammatory factors. Additionally, Gypenoside XLIX inhibited ROS levels and NLRP3 inflammasome, possibly mediated by the Sirt1/Nrf2 signaling pathway. Moreover, Gypenoside XLIX significantly inhibited sepsis-induced lung cell apoptosis and excessive autophagy of mitochondria. Specifically, it suppressed mitochondrial pathway apoptosis and the Pink1/Parkin pathway of mitochondrial autophagy. These findings reveal the multifaceted effects of Gypenoside XLIX in anti-inflammatory, antioxidative, and inhibition of cell apoptosis and autophagy. This provides strong support for its therapeutic potential in sepsis-related lung injuries.

Tongfu Lifei Decoction Attenuated Sepsis-Related Intestinal Mucosal Injury Through Regulating Th17/Treg Balance and Modulating Gut Microbiota.

Intestinal damage and secondary bacterial translocation are caused by the inflammatory response induced by sepsis. Tongfu Lifei (TLF) decoction has a protective effect on sepsis-related gastrointestinal function injury. However, the relation between gut microbiota, immune barrier, and sepsis under the treatment of TLF have not been well clarified yet. Here, rats were subjected to cecal ligation and puncture (CLP) to create a sepsis model. Subsequently, the TLF decoction was given to CLP rats by gavage, fecal microbiota transplantation (FMT), and antibiotic were used as positive control. TLF suppressed the inflammatory response and improved the pathological changes in the intestines of CLP rats. Besides, TLF promoted the balance of the percentage of the Th17 and Treg cells. Intestinal barrier function was also improved by TLF through enhancing ZO-1, and Occludin and Claudin 1 expression, preventing the secondary translocation of other gut microbiota. TLF dramatically boosted the gut microbiota's alpha- and beta-diversity in CLP rats. Moreover, it increased the relative abundance of anti-inflammatory gut microbiota and changed the progress of the glucose metabolism. In short, TLF regulated the gut microbiota to balance the ratio of Th17/Treg cells, reducing the inflammation in serum and intestinal mucosal injury in rats.

Association between neck circumference and bone mineral loss: A cross-sectional study in Sichuan province in China.

BACKGROUND: The associations of fat distribution with bone health are debatable. We aimed to investigate the associations between neck circumference (NC) and bone mineral loss among the adult Chinese population in Sichuan province. METHODS: We examined overall NC size and NC stratums (≤35 cm, 3538 cm) with bone mineral density (BMD) at the femoral neck, lumbar spine, total hip skeletal sites in 135 men and 479 women respectively, and assessed whether adiposity, lipids, and calcium and phosphorus levels, might have a biased role in the relationship of NC and bone mineral loss with linear regression, logistic regression, and restricted cubic spline models. RESULTS: The overall NC size is not independently associated with BMD at all sites. However, stratification for NC revealed that the positive correlation between NC and BMD at all sites were significant in the NC stratum 1 (≤35 cm) in women (all p < 0.05) and NC stratum 2 (3538 cm) compared with NC stratum 1 using logistic regression. However, in women, no statistically significant association was observed between NC stratum 1 and BMD values after adjustment for the same confounders. CONCLUSIONS: Our findings suggest a NC stratum-specific association between NC size and bone mineral loss in men in Sichuan province in China, but not in women.

Pyroptosis: Mechanisms and links with diabetic cardiomyopathy.

Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycaemia that seriously affects human health. Diabetic cardiomyopathy (DCM) is a major cardiovascular complication and one of the main causes of death in patients with DM. Although DCM attracts great attention, and new therapeutic methods are continuously developed, there is a lack of effective treatment strategies. Therefore, exploring and targeting new signalling pathways related to the evolution of DCM becomes a hotspot and difficulty in the prevention and treatment of DCM. Pyroptosis is a newly discovered regulated cell death that is heavily dependent on the formation of plasma membrane pores by members of the gasdermin protein family and is reported to be involved in the occurrence, development, and pathogenesis of DCM. In this review, we focus on the molecular mechanisms of pyroptosis, its involvement in the relevant signalling pathways of DCM, and potential pyroptosis-targeting therapeutic strategies for the treatment of DCM. Our review provides new insights into the use of pyroptosis as a useful tool for the prevention and treatment of DCM and clarifies future research directions.

Fracture-related wound infections following surgical treatment of fractures in HIV-positive and HIV-negative patients: A meta-analysis.

The meta-analysis aims to evaluate and compare fracture-associated wound infections (FAWIs) following surgical treatment of fractures in human immunodeficiency virus (HIV)-positive and HIV-negative patients. Examinations comparing HIV-negative to HIV-negative for fracture was among the meta-analysis from various languages that met the inclusion criteria. Using dichotomous random or fixed models, the results of these investigations were examined, and the Odds ratio (OR) with 95% confidence intervals was computed (CIs). 14 examinations from 1991 to 2023 were recruited for the current analysis including 3528 personals with fractures. HIV-positive had significantly higher FAWI before antiretroviral (OR, 3.59; 95% CI, 2.01-6.41, p < 0.001) compared to HIV-negative personals with fractures. However, no significant difference was found between HIV-positive and HIV-negative in FAWI after antiretroviral (OR, 0.58; 95% CI, 0.30-1.12, p = 0.10) in personals with fractures. The examined data revealed that HIV-positive had significantly higher FAWI before antiretroviral, however, no significant difference was found in FAWI after antiretroviral compared to HIV-negative personals with fractures. Nevertheless, caution should be exercised while interacting with its values since some of the chosen examinations were found with a low sample size and a low number of examinations were found for the comparisons studied for the meta-analysis.

Liensinine reduces acute lung injury brought on by lipopolysaccharide by inhibiting the activation of the NF-κB signaling pathway through modification of the Src/TRAF6/TAK1 axis.

ALI is characterized by macrophage-driven inflammation, causing severe lung damage. Currently, there are limited therapeutic options available for ALI. Liensinine (LIEN), with known anti-inflammatory properties, lacks extensive study in the ALI context. This study aimed to investigate the impact of LIEN on ALI and elucidate its molecular mechanisms. A total of thirty-six male BALB/c mice altogether were split into six groups: Control, LPS (10 mg/kg), Low (10 mg/kg LIEN + 10 mg/kg LPS), Middle (20 mg/kg LIEN + 10 mg/kg LPS), High (40 mg/kg LIEN + 10 mg/kg LPS), and DEX (2 mg/kg DEX + 10 mg/kg LPS). Lung tissue injury, pulmonary edema, and inflammatory factor levels were evaluated in lung tissues and LPS-stimulated bone marrow-derived macrophages (BMDM). TAK1 activation, TRAF6 ubiquitination, and their interactions were assessed to understand the involved molecular mechanisms. LIEN treatment ameliorated lung tissue injury and suppressed LPS-induced inflammatory factor levels in lung tissues and BMDM. Mechanistically, LIEN inhibited TAK1 activation by disrupting TRAF6-TAK1 interactions, limiting p65's nuclear translocation, and reducing the release of inflammatory factors. According to network pharmacology and molecular docking, LIEN most likely prevents inflammation by interfering directly with the Src. Overexpression of Src in BMDM abolished the regulation of TRAF6 by LIEN, supporting the involvement of the Src/TRAF6/TAK1 axis in its mechanism of action. Based on this study, LIEN treats ALI by modifying the Src/TRAF6/TAK1 axis and blocking the activation of the NF-κB pathway, regulating the release of inflammatory factors. These findings highlight the promise of LIEN as a prospective therapeutic option for the treatment of ALI.

METTL14 knockdown inhibits the pyroptosis in the sepsis-induced acute lung injury through regulating the m6A modification of NLRP3.

Background: Sepsis has become one of the main factors inducing the development of acute lung injury (ALI) in clinical practice. Currently, inhibiting the activation of NLRP3 mediated pyroptosis is the target of multiple drugs in the treatment of sepsis induced ALI. This study aimed to explore the effects of METTL14 on the pyroptosis in the sepsis induced ALI progression.Methods: LPS-stimulated A549 cells and cecal ligation and puncture (CLP)-treated mice were used to establish the ALI model in vitro and in vivo. Then, the cell viability was measured by CCK-8 assay. ELISA kits were used to determine the IL-18 and IL-1ß contents. Pyroptosis rate was tested by flow cytometry. M6A dot blot was conducted to analyze the global m6A levels and MeRIP assay was performed to detect the m6A levels of NLRP3. The relationship between METTL14 and NLRP3 was confirmed by RIP and dual-luciferase report assays.Results: The global m6A levels were significantly increased in the LPS-stimulated A549 cells and CLP-treated mice. METTL14 knockdown decreased the cell viability, IL-18 and IL-1ß contents, and pyroptosis rate of the LPS-stimulated A549 cells. Furthermore, the increase of pyroptosis-related proteins in LPS-stimulated A549 cells was significantly decreased after METTL14 knockdown. Additionally, METTL14 knockdown decreased the m6A and mRNA levels of NLRP3, and NLRP3 overexpression reversed the effects of METTL14 knockdown on the pyroptosis in the LPS-stimulated A549 cells. In CLP-treated mice, METTL14 knockdown relieved the injury and decreased the IL-18 and IL-1ß contents in the lung tissues, serum and bronchoalveolar lavage fluid.Conclusion: This study demonstrated that METTL14 knockdown inhibited the pyroptosis in the sepsis-induced ALI progression through decreasing the NLRP3 levels dependent on m6A methylation modification.

LI-RADS category 3, 4, and M observations: a multiple parameters diagnostic model for hepatocellular carcinoma.

BACKGROUND: Hepatic lesions categorized as LR-3, LR-4, and LR-M are challenging to accurately assess and diagnose. PURPOSE: To combine potential clinical and/or magnetic resonance imaging (MRI) features for a more comprehensive hepatocellular carcinoma (HCC) versus non-HCC diagnosis for patients with LR-3, LR-4, and LR-M graded lesions. METHODS: Data were consecutively retrieved from 82 at-risk patients with LR-3 (n = 43), LR-4 (n = 20), and LR-M (n = 23) lesions. Significant findings for the differentiation of HCC and non-HCC, including MRI features and clinical factors, were identified with univariable and multivariable analyses. The variables for a prediction model were selected through stepwise use of Akaike's Information Criterion (AIC) to build multivariable logistic regression model. RESULTS: Serum alpha-fetoprotein (AFP) >16.2 ng/mL (odds ratio [OR] = 22.4; P = 0.006), septum (OR = 52.1; P = 0.011), and hepatobiliary phase (HBP) hypointensity (OR = 40.2; P = 0.001) were confirmed as independent predictors of HCC. When combining the three predictors and mild-moderate T2 hyperintensity, the model (AIC = 50.91) showed good accuracy with a C-index of 0.948. CONCLUSION: In at-risk patients with LR-3, LR-4, or LR-M lesions, integrating AFP, septum, HBP hypointensity, and mild-moderate T2 hyperintensity achieved high diagnostic performance for the diagnosis of HCC.

Pseudomonas aeruginosa-induced mitochondrial dysfunction inhibits proinflammatory cytokine secretion and enhances cytotoxicity in mouse macrophages in a reactive oxygen species (ROS)-dependent way. / 铜绿假单胞菌诱导的线粒体功能障碍以ROSä¾èµ–æ€§çš„æ–¹å¼æŠ‘åˆ¶ä¿ƒç‚Žç»†èƒžå› å­åˆ†æ³Œå¹¶å¢žå¼ºå°é¼ å·¨å™¬ç»†èƒžçš„ç»†èƒžæ¯’æ€§.

Pseudomonas aeruginosa belongs to the genus Pseudomonas and is a common Gram-negative, exclusively aerobic, conditionally pathogenic bacterium with the characteristics of easy colonization, mutation, and multidrug resistance (Deng et al., 2015; Azam and Khan, 2019; Jurado-Martín et al., 2021). It is mainly distributed in the air, soil, water, intestinal tract, and skin surface of humans and domestic animals and can cause complications such as ulcerative keratitis, otitis externa, skin and soft tissue infections, respiratory infections, sepsis, osteomyelitis, endocarditis, and urinary tract infections in burned or immunocompromised patients (Azam and Khan, 2019; Chai and Xu, 2020; Voth et al., 2020). P. aeruginosa is a naturally drug-resistant bacterium that is resistant to a wide range of antibiotics, making it one of the major opportunistic pathogens leading to in-hospital infections (Pang et al., 2019; Chai and Xu, 2020; Reynolds and Kollef, 2021). According to the surveillance report of the China Antimicrobial Resistance Surveillance System (CARSS, http://www.carss.cn), Gram-negative bacteria accounted for more than 70% of all bacterial infections, and P. aeruginosa accounted for 12.4%, 12.0%, and 12.2% in 2018, 2019, and 2020, respectively. Therefore, P. aeruginosa infection has become an important concern in public health care, and it is particularly important to gain insight into the means of host immune defense against P. aeruginosa infection.

Strengthen high-loading operation of wastewater treatment plants by composite micron powder carrier: Microscale control of carbon, nitrogen, and sulfur metabolic pathways.

The concentration of activated sludge is a crucial factor influencing the capacity and efficiency of sewage wastewater treatment plants (WWTPs). However, high sludge concentrations can lead to sludge loss in the secondary sedimentation tank, resulting in reduced processing capacity, particularly during low-temperature stages and sludge bulking. This study investigated the impact of adding composite micron powder carriers (CMPC) in high-concentration powder carrier biofluidized bed (HPB) technology to the biochemical units of WWTPs on sludge concentration and settling performance. For the traditional activated sludge method (ASM), its hydraulic retention time (HRT) was 8 h, with an average effluent total nitrogen (TN) of 15.14 mg/L. Sludge bulking was prone to occur in low-temperature environments, resulting in a high average sludge volume index (SVI) of 560 mL/g. Conversely, with a CMPC dosage of 4 g/L, the HRT of HPB technology was 4.8 h, and the average effluent TN was 11.40 mg/L, with a removal efficiency of 67.43 %. During operation of HPB technology under high sludge concentration conditions (8 g/L), the average SVI remained at 85 mL/g, indicating excellent settling characteristics. Moreover, in the sequencing batch reactor (SBR), the SVI value of bulking sludge decreased from the original 695 to 111 mL/g by the 9th day of operation with the CMPC dosage of 2 g/L. At the same time, the filamentous bacteria almost disappeared, suggesting that CMPC inhibit the growth of filamentous bacteria. Metagenomic analysis demonstrated that CPMC enhance the utilization of small molecular fatty acids in activated sludge and promote electron transfer between nitrate and nitrite, thereby improving wastewater treatment capacity. Additionally, CMPC enhanced the relative abundance of Saprospiraceae in sludge, which accelerate the degradation of polysaccharides in extracellular polymeric substances, weaken sludge's hydrophilic properties, and improve sludge's settling performance. Overall, these findings suggested that CMPC effectively strengthen the high-loading operation of WWTPs by improving sludge concentration and sedimentation performance.

Liensinine pretreatment reduces inflammation, oxidative stress, apoptosis, and autophagy to alleviate sepsis acute kidney injury.

Liensinine is mainly derived from alkaloids extracted and isolated from lotus seeds (Nelumbo nucifera Gaertn). It possesses anti-inflammatory, and antioxidant, according to contemporary pharmacological investigations. However, the effects and therapeutic mechanisms of liensinine on acute kidney injury (AKI) models of sepsis are unclear. To gain insight into these mechanisms, we established a sepsis kidney injury model by LPS injection of mice treated with liensinine, and stimulation of HK-2 with LPS in vitro and treated with liensinine and inhibitors of p38 MAPK, JNK MAPK. We first found that liensinine significantly reduced kidney injury in sepsis mice, while suppressing excessive inflammatory responses, restoring renal oxidative stress-related biomarkers, reducing increased apoptosis in TUNEL-positive cells and excessive autophagy, and that this process was accompanied by an increase in JNK/ p38-ATF 2 axis. In vitro experiments further demonstrated that lensinine reduced the expression of KIM-1, NGAL, inhibited pro- and anti-inflammatory secretion disorders, regulated the activation of the JNK/p38-ATF 2 axis, and reduced the accumulation of ROS, as well as the reduction of apoptotic cells detected by flow cytometry, and that this process played the same role as that of p38 MAPK, JNK MAPK inhibitors. We speculate that liensinine and p38 MAPK, JNK MAPK inhibitors may act on the same targets and could be involved in the mechanism of alleviating sepsis kidney injury in part through modulation of the JNK/p38-ATF 2 axis. Our study demonstrates that lensinine is a potential drug and thus provides a potential avenue for the treatment of AKI.

Stacking Multiple Genes Improves Resistance to Chilo suppressalis, Magnaporthe oryzae, and Nilaparvata lugens in Transgenic Rice.

The ability of various pests and diseases to adapt to a single plant resistance gene over time leads to loss of resistance in transgenic rice. Therefore, introduction of different pest and disease resistance genes is critical for successful cultivation of transgenic rice strains with broad-spectrum resistance to multiple pathogens. Here, we produced resistance rice lines with multiple, stacked resistance genes by stacking breeding and comprehensively evaluated their resistance to Chilo suppressalis (striped rice stemborer), Magnaporthe oryzae (rice blast), and Nilaparvata lugens (brown planthopper) in a pesticide-free environment. CRY1C and CRY2A are exogenous genes from Bacillus thuringiensis. Pib, Pikm, and Bph29 are natural genes in rice. CH121TJH was introduced into CRY 1C, Pib, Pikm, and Bph29. CH891TJH and R205XTJH were introduced into CRY 2A, Pib, Pikm, and Bph29. Compared with those observed in their recurrent parents, CH121TJH significantly increased the mortality of borers. The other two lines CH891TJH and R205XTJH are the same result. Three lines introduction of Pib and Pikm significantly reduced the area of rice blast lesions, and introduction of Bph29 significantly reduced seedling mortality from N. lugens. Introduction of the exogenous genes had relatively few effects on agronomic and yield traits of the original parents. These findings suggest that stacking of rice resistance genes through molecular marker-assisted backcross breeding can confer broad spectrum and multiple resistance in differently genetic backgrounds.

Protective effect of quercetin on avermectin induced splenic toxicity in carp: Resistance to inflammatory response and oxidative damage.

Avermectin pollution is an important problem that cannot be ignored in aquatic system in recent years. It has brought great trouble to freshwater aquaculture, especially fishery aquaculture. Plant-derived quercetin has anti-inflammatory and antioxidant properties and is widely used as a dietary additive, but its protective effect on immune damage induced by avermectin in freshwater carp remains unclear. This study evaluated the role of dietary additive quercetin supplementation in chronic avermectin exposure of carp spleen. Sixty carp were divided into 4 groups (n = 15/ group), including control group, avermectin treatment group, quercetin treatment group, quercetin and avermectin co-treatment group. Carp were exposed to a 1/10 96 h LC50 dose of avermectin for 30 d and fed a carp diet containing 400 mg/kg quercetin twice a day (3% body weigh/ carp). The results showed that chronic avermectin exposure caused the loose parenchymal structure of carp spleen tissue and the increase of inflammatory cells, accompanied by increased transcription levels of pro-inflammatory il-1ß, il-6, tnf-α and decreased levels of anti-inflammatory factors il-10 and tgf-ß1, ROS accumulation in spleen tissue. MDA content increased and T-AOC, CAT and GSH levels decreased. Quercetin down-regulates the NF-κB pathway by inhibiting the expression of iNOS and activating p38 MAPK, blocking the transcription of inflammatory factors, and alleviating the inflammation of carp spleen caused by chronic avermectin exposure. In addition, quercetin inhibits the over-activation of Nrf2/Keap-1 signaling axis, blocks ROS accumulation, and restores the spleen REDOX homeostasis. In conclusion, quercetin, as a dietary additive for carp feed, can effectively improve the immune damage caused by avermectin pollution in aquatic environment, resist spleen inflammation and oxidative stress, and provide a theoretical basis for clinical development of freshwater carp feed.

Effect of Bifidobacterium on osteoclasts: TNF-α/NF-κB inflammatory signal pathway-mediated mechanism.

Osteoporosis is a systemic multifactorial bone disease characterized by low bone quality and density and bone microstructure damage, increasing bone fragility and fracture vulnerability. Increased osteoclast differentiation and activity are important factors contributing to bone loss, which is a common pathological manifestation of bone diseases such as osteoporosis. TNF-a/NF-κB is an inflammatory signaling pathway with a key regulatory role in regulating osteoclast formation, and the classical pathway RANKL/RANK/OPG assists osteoclast formation. Activation of this inflammatory pathway promotes the formation of osteoclasts and accelerates the process of osteoporosis. Recent studies and emerging evidence have consistently demonstrated the potential of probiotics to modulate bone health. Secretions of Bifidobacterium, a genus of probiotic bacteria in the phylum Actinobacteria, such as short-chain fatty acids, equol, and exopolysaccharides, have indicated beneficial effects on bone health. This review discusses the molecular mechanisms of the TNF-a/NF-κB inflammatory pathway in regulating osteoclast formation and describes the secretions produced by Bifidobacterium and their potential effects on bone health through this pathway, opening up new directions for future research.

Mechanisms regarding respiratory toxicity triggered by accumulation of ROS in carp exposed to difenoconazole.

Difenoconazole is a widely used but difficult-to-degrade fungicide that can directly affect aquatic ecosystems. Here, two doses (0.488 mg/L, 1.953 mg/L) of difenoconazole were used to study the toxicity to the respiratory system of carp at an exposure time of 96 h. The results showed that difenoconazole exposure resulted in severe structural damage to carp gill tissue with extensive inflammatory cell infiltration. Mechanistically, difenoconazole exposure led to excessive accumulation of ROS in carp gill tissue, which induced an inflammatory response in the gill tissue. Meanwhile, the activities of SOD and CAT were reduced and the NRF2 signaling pathway was activated to regulate the imbalance between oxidation and antioxidation. In addition, difenoconazole exposure further activated the mitochondrial pathway of apoptosis by upregulating cytochrome C, BAX, cleaved-caspase 9, and downregulating Bcl-2. More interestingly, exposure to difenoconazole increased autophagosomes, but lysosomal dysfunction prevented the late stages of autophagy from proceeding smoothly, resulting in a protective autophagic response that is not properly initiated. In summary, difenoconazole exposure caused respiratory toxicity including inflammation response, oxidative stress, apoptosis, and autophagy in carp through the accumulation of ROS. The present study expanded our understanding of the toxic effects of difenoconazole on organisms and its possible threat to the aquatic environment.