Gut microbes combined with metabolomics reveal the protective effects of Qijia Rougan decoction against CCl4-induced hepatic fibrosis.

Background: The occurrence and development of Hepatic fibrosis (HF) are closely related to the gut microbial composition and alterations in host metabolism. Qijia Rougan decoction (QJ) is a traditional Chinese medicine compound utilized clinically for the treatment of HF with remarkable clinical efficacy. However, its effect on the gut microbiota and metabolite alterations is unknown. Therefore, our objective was to examine the impact of QJ on the gut microbiota and metabolism in Carbon tetrachloride (CCl4)-induced HF. Methods: 40% CCl4 was used to induce HF, followed by QJ administration for 6 weeks. Serum biochemical analyses, histopathology, immunohistochemistry, RT-PCR, 16S rRNA gene sequencing, and non-targeted metabolomics techniques were employed in this study to investigate the interventional effects of QJ on a CCl4-induced HF model in rats. Results: This study demonstrated that QJ could effectively ameliorate CCl4-induced hepatic inflammation and fibrosis. Moreover, QJ upregulated the expression of intestinal tight junction proteins (TJPs) and notably altered the abundance of some gut microbes, for example, 10 genera closely associated with HF-related indicators and TJPs. In addition, metabolomics found 37 key metabolites responded to QJ treatment and strongly associated with HF-related indices and TJPs. Furthermore, a tight relation between 10 genera and 37 metabolites was found post correlation analysis. Among them, Turicibacter, Faecalibaculum, Prevotellaceae UCG 001, and unclassified Peptococcaceae may serve as the core gut microbes of QJ that inhibit HF. Conclusion: These results suggest that QJ ameliorates hepatic inflammation and fibrosis, which may be achieved by improving intestinal tight junctions and modulating gut microbiota composition as well as modulating host metabolism.

High-throughput sequencing-based analysis of the composition and diversity of the endophyte community in roots of Stellera chamaejasme.

Stellera chamaejasme (S. chamaejasme) is an important medicinal plant with heat-clearing, detoxifying, swelling and anti-inflammatory effects. At the same time, it is also one of the iconic plants of natural grassland degradation in northwest China, playing a key role in the invasion process. Plant endophytes live in healthy plant tissues and can synthesize substances needed for plant growth, induce disease resistance in host plants, and enhance plant resistance to environmental stress. Therefore, studying the root endophytes of S. chamaejasme is of great significance for mining beneficial microbial resources and biological prevention and control of S. chamaejasme. This study used Illumina MiSeq high-throughput sequencing technology to analyze the composition and diversity of endophytes in the roots of S. chamaejasme in different alpine grasslands (BGC, NMC and XGYZ) in Tibet. Research results show that the main phylum of endophytic fungi in the roots of S. chamaejasme in different regions is Ascomycota, and the main phyla of endophytic bacteria are Actinobacteria, Proteobacteria and Firmicutes (Bacteroidota). Overall, the endophyte diversity of the NMC samples was significantly higher than that of the other two sample sites. Principal coordinate analysis (PCoA) and permutational multivariate analysis of variance (PERMANOVA) results showed significant differences in the composition of endophytic bacterial and fungal communities among BGC, NMC and XGYZ samples. Co-occurrence network analysis of endophytes showed that there were positive correlations between fungi and some negative correlations between bacteria, and the co-occurrence network of bacteria was more complex than that of fungi. In short, this study provides a vital reference for further exploring and utilizing the endophyte resources of S. chamaejasme and an in-depth understanding of the ecological functions of S. chamaejasme endophytes.

Salvia miltiorrhiza suppresses cardiomyocyte ferroptosis after myocardial infarction by activating Nrf2 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Ferroptosis, a recently identified non-apoptotic form of cell death reliant on iron, is distinguished by an escalation in lipid reactive oxygen species (ROS) that are iron-dependent. This phenomenon has a strong correlation with irregularities in iron metabolism and lipid peroxidation. Salvia miltiorrhiza Bunge (DS), a medicinal herb frequently utilized in China, is highly esteemed for its therapeutic effectiveness in enhancing blood circulation and ameliorating blood stasis, particularly during the treatment of cardiovascular diseases (CVDs). Numerous pharmacological studies have identified that DS manifests antioxidative stress effects as well as inhibits lipid peroxidation. However, ambiguity persists regarding the potential of DS to impede ferroptosis in cardiomyocytes and subsequently improve myocardial damage post-myocardial infarction (MI). AIM OF THE STUDY: The present work focused on investigating whether DS could be used to prevent the ferroptosis of cardiomyocytes and improve post-MI myocardial damage. MATERIALS AND METHODS: In vivo experiments: Through ligation of the left anterior descending coronary artery, we constructed both a wild-type (WT) and NF-E2 p45-related factor 2 knockout (Nrf2-/-) mouse model of MI. Effects of DS and ferrostatin-1 (Fer-1) on post-MI cardiomyocyte ferroptosis were examined through detecting ferroptosis and myocardial damage-related indicators as well as Nrf2 signaling-associated protein levels. In vitro experiments: Erastin was used for stimulating H9C2 cardiomyocytes to construct an in vitro ferroptosis cardiomyocyte model. Effects of DS and Fer-1 on cardiomyocyte ferroptosis were determined based on ferroptosis-related indicators and Nrf2 signaling-associated protein levels. Additionally, inhibitor and activator of Nrf2 were used for confirming the impact of Nrf2 signaling on DS's effect on cardiomyocyte ferroptosis. RESULTS: In vivo: In comparison to the model group, DS suppressed ferroptosis in cardiomyocytes post-MI and ameliorated myocardial damage by inducing Nrf2 signaling-related proteins (Nrf2, xCT, GPX4), diminishing tissue ferrous iron and malondialdehyde (MDA) content. Additionally, it enhanced glutathione (GSH) levels and total superoxide dismutase (SOD) activity, effects that are aligned with those of Fer-1. Moreover, the effect of DS on alleviating cardiomyocyte ferroptosis after MI could be partly inhibited through Nrf2 knockdown. In vitro: Compared with the erastin group, DS inhibited cardiomyocyte ferroptosis by promoting the expression of Nrf2 signaling-related proteins, reducing ferrous iron, ROS, and MDA levels, but increasing GSH content and SOD activity, consistent with the effect of Fer-1. Additionally, Nrf2 inhibition increased erastin-mediated ferroptosis of cardiomyocytes through decreasing Nrf2 signaling-related protein expressions. Co-treatment with DS and Nrf2 activator failed to further enhance the anti-ferroptosis effect of DS. CONCLUSION: MI is accompanied by cardiomyocyte ferroptosis, whose underlying mechanism is probably associated with Nrf2 signaling inhibition. DS possibly suppresses ferroptosis of cardiomyocytes and improves myocardial damage after MI through activating Nrf2 signaling.

[Role of NLRP3 inflammasome in prevention and treatment of cognitive impairment-related diseases and traditional Chinese medicine intervention: a review].

Alzheimer's disease(AD), vascular dementia(VD), and traumatic brain injury(TBI) are more common cognitive impairment diseases characterized by high disability and mortality rates, imposing a heavy burden on individuals and their families. Although AD, VD, and TBI have different specific mechanisms, their pathogenesis is closely related to the nucleotide-binding oligome-rization domain-like receptor protein 3(NLRP3). The NLRP3 inflammasome is involved in neuroinflammatory responses, mediating microglial polarization, regulating the reduction of amyloid ß-protein(Aß) deposition, neurofibrillary tangles(NFTs) formation, autophagy regulation, and maintaining brain homeostasis, and synaptic stability, thereby contributing to the development of AD, VD, and TBI. Previous studies have shown that traditional Chinese medicine(TCM) can alleviate neuroinflammation, promote microglial polarization towards the M2 phenotype, reduce Aß deposition and NFTs formation, regulate autophagy, and maintain brain homeostasis by intervening in NLRP3 inflammasome, hence exerting a role in preventing and treating cognitive impairment-related diseases, reducing psychological and economic pressure on patients, and improving their quality of life. Therefore, this article elucidated the role of NLRP3 inflammasome in AD, VS, and TBI, and provided a detailed summary of the latest research results on TCM intervention in NLRP3 inflammasome for the prevention and treatment of these diseases, aiming to inherit the essence of TCM and provide references and foundations for clinical prevention and treatment of cognitive impairment-related diseases with TCM. Meanwhile, this also offers insights and directions for further research in TCM for the prevention and treatment of cognitive impairment-related diseases.

[Role of NLRP3 inflammasome in heart failure and traditional Chinese medicine intervention: a review].

Heart failure is characterized by high incidence and mortality rates, and the search for effective treatment strategies for heart failure and the improvement of clinical outcomes have always been important research directions. Imbalanced inflammation has been proven to be one of the critical pathological factors in heart failure, positively correlated with adverse events such as impaired cardiac function and myocardial fibrosis. In recent years, studies have confirmed that the activation of the NOD-like receptor thermal protein domain-associated protein 3(NLRP3) inflammasome plays a common regulatory role in the inflammation imbalance induced by various factors in heart failure. Moreover, certain traditional Chinese medicine(TCM) and active components can significantly inhibit the activation of the NLRP3 inflammasome, thereby improving heart failure. This article first overviewed the basic information about the NLRP3 inflammasome, summarized the regulatory mechanisms of the NLRP3 inflammasome in heart failure induced by various factors, introduced recent research progress on TCM and active components that inhibited the NLRP3 inflammasome to improve heart failure, aiming to provide references for innovative drug research in the field of integrated Chinese and western medicine for the prevention and treatment of heart failure.

Protective effects of sodium humate and its zinc and selenium chelate on the oxidative stress, inflammatory, and intestinal barrier damage of Salmonella Typhimurium-challenged broiler chickens.

The objective of this study was to investigate the protective effects and mechanisms of dietary administration of sodium humate (HNa) and its zinc and selenium chelate (Zn/Se-HNa) in mitigating Salmonella Typhimurium (S. Typhi) induced intestinal injury in broiler chickens. Following the gavage of 109 CFU S. Typhi to 240 broilers from 21-d to 23-d aged, various growth performance parameters such as body weight (BW), average daily gain (ADG), average daily feed intake (ADFI), and feed ratio (FCR) were measured before and after infection. Intestinal morphology was assessed to determine the villus height, crypt depth, and chorionic cryptologic ratio. To evaluate intestinal barrier integrity, levels of serum diamine oxidase (DAO), D-lactic acid, tight junction proteins, and the related genes were measured in each group of broilers. An analysis was conducted on inflammatory-related cytokines, oxidase activity, and Nuclear Factor Kappa B (NF-κB) and Nuclear factor erythroid2-related factor 2 (Nrf2) pathway-related proteins and mRNA expression. The results revealed a significant decrease in BW, ADG, and FCR in S. typhi-infected broilers. HNa tended to increase FCR (P = 0.056) while the supplementation of Zn/Se-HNa significantly restored BW and ADG (P < 0.05). HNa and Zn/Se-HNa exhibit favorable and comparable effects in enhancing the levels of serum DAO, D-lactate, and mRNA and protein expression of jejunum and ileal tight junction. In comparison to HNa, Zn/Se-HNa demonstrates a greater reduction in S. Typhi shedding in feces, as well as superior efficacy in enhancing the intestinal morphology, increasing serum catalase (CAT) activity, inhibiting pro-inflammatory cytokines, and suppressing the activation of the NF-κB pathway. Collectively, Zn/Se-HNa was a more effective treatment than HNa to alleviate adverse impact of S. Typhi infection in broiler chickens.

Acute effects of different Tai Chi practice protocols on cardiac autonomic modulation.

Tai Chi serves as an effective exercise modality for enhancing autonomic regulation. However, a majority of existing studies have employed the single routine (SR) protocol as the basis for health interventions. The extent to which the gong routine application (GRA) protocol achieves similar levels of exercise load stimulation as traditional single practice routines remains uncertain. Therefore, this study the distinct characteristics of autonomic load stimulation in these different protocols, thus providing a biological foundation to support the development of Tai Chi health promotion intervention programs. we recruited a cohort of forty-five university students to participate in the 15 min GRA protocol and SR protocol. We collected heart rate and heart rate variability indicators during periods of rest, GRA protocol, and SR protocol utilizing the Polar Scale. Additionally, we assessed the mental state of the participants using the BFS State of Mind Scale. In summary, the autonomic load is lower in the GRA protocol compared to the SR protocol, with lower sympathetic activity but higher parasympathetic activity in the former. Results are specific to college students, additional research is necessary to extend support for frail older adults. It is advised to incorporate GRA protocol alongside SR protocol in Tai Chi instruction. This approach is likely to enhance Tai Chi skills and yield greater health benefits.

Shengu granules ameliorate ovariectomy-induced osteoporosis by the gut-bone-immune axis.

Introduction: Postmenopausal osteoporosis (PMOP) is a common chronic disease, and the loss of bone density and bone strength after menopause are its main symptoms. Effective treatments for PMOP are still uncertain, but Chinese medicine has some advantages in slowing down bone loss. Shengu granules are often used clinically to treat PMOP. It has been shown to be an effective prescription for the treatment of PMOP, and there is evidence that gut flora may play an important role. However, whether Shengu granules attenuate PMOP by modulating gut flora and related mechanisms remains unclear. Methods: In this study, we mainly examined the bone strength of the femur, the structure of the intestinal microbiota, SCFAs in the feces and the level of FOXP3 cells in the colon. To further learn about the inflammation response, the condition of the mucosa and the level of cytokines in the serum also included in the testing. In addition, to get the information of the protein expression, the protein expression of OPG and RANKL in the femur and the protein expression of ZO-1 and Occludin in the colon were taken into account. Results: The osteoporosis was significantly improved in the SG group compared with the OVX group, and the diversity of intestinal flora, the secretion level of SCFAs and the expression level of FOXP3 were significantly increased compared with the OVX group. In terms of inflammatory indicators, the intestinal inflammation scores of the SG group was significantly lower than those in the OVX group. Additionally, the serum expression levels of IL-10 and TGF-ß in the SG group were significantly increased compared with the OVX group, and the expression levels of IL-17 and TNF-α were significantly decreased compared with the OVX group. In terms of protein expression, the expression levels of ZO-1, Occluding and OPG were significantly increased in the SG group compared with the OVX group, and the expression level of RANKL was significantly decreased compared with the OVX group. Discussion: Shengu granules treatment can improve the imbalance of intestinal flora, increase the secretion of SCFAs and the expression of FOXP3, which reduces the inflammatory response and repairs the intestinal barrier, as well as regulates the expression of OPG/RANKL signaling axis. Overall, Shengu granules ameliorate ovariectomy-induced osteoporosis by the gut-bone-immune axis.

A Natural Peptide from A Traditional Chinese Medicine Has the Potential to Treat Chronic Atrophic Gastritis by Activating Gastric Stem Cells.

Chronic atrophic gastritis (AG) is initiated mainly by Helicobacter pylori infection, which may progress to stomach cancer following the Correa's cascade. The current treatment regimen is H. pylori eradication, yet evidence is lacking that this treatment is effective on later stages of AG especially gastric gland atrophy. Here, using AG mouse model, patient samples, gastric organoids, and lineage tracing, this study unraveled gastric stem cell (GSC) defect as a crucial pathogenic factor in AG in mouse and human. Moreover, a natural peptide is isolated from a traditional Chinese medicine that activated GSCs to regenerate gastric epithelia in experimental AG models and revitalized the atrophic gastric organoids derived from patients. It is further shown that the peptide exerts its functions by stabilizing the EGF-EGFR complex and specifically activating the downstream ERK and Stat1 signaling. Overall, these findings advance the understanding of AG pathogenesis and open a new avenue for AG treatment.

[Expert consensus on integrated traditional Chinese and western medicine diagnosis and treatment for osteoporotic fractures].

Osteoporotic fractures represent the most severe complications of osteoporosis,characterized by insidious onset,high mortality and disability rates,and a steadily increasing incidence,imposing a significant socioeconomic burden. Western medicine has advantages in diagnosis and surgical interventions,while traditional Chinese medicine excels in holistic management and the restoration of bodily equilibrium. The integration of both traditional Chinese medicine (TCM) and western medicine emerges as an effective therapeutic strategy for osteoporotic fractures. In order to propagate the concept of integrated diagnosis and treatment,foster the advancement of integrated medical techniques for osteoporotic fractures,and establish standardized and normative protocols for disease prevention,diagnosis,and treatment,a consensus expert group,led by Geriatric Branch of Chinese Geriatrics Society,the Young Osteoporosis Group of Orthopedics Branch of Chinese Medical Association,Osteoporosis Group of Orthopedics Branch of Chinese Physician Association,and Osteoporosis Professional Committee of the Shanghai Society of Integrated Traditional Chinese and Western Medicine,was established. This group engaged in deliberations and formulated the "Expert Consensus on Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment of Osteoporotic Fractures" elucidating the concept of integrated medicine and offering recommendations in the domains of prevention,diagnosis,and treatment,with the aspiration of ameliorating the prognosis of osteoporotic fractures and enhancing the quality of life for these patients.

Analysis of the gut microbiome in sled dogs reveals glucosamine- and activity-related effects on gut microbial composition.

The composition of the microbiome influences many aspects of physiology and health, and can be altered by environmental factors, including diet and activity. Glucosamine is a dietary supplement often administered to address arthritic symptoms in humans, dogs, and other mammals. To investigate how gut microbial composition varies with glucosamine supplementation, we performed 16S rRNA sequence analysis of fecal samples from 24 Alaskan and Inuit huskies and used mixed effects models to investigate associations with activity, age, and additional factors. Glucosamine ingestion, age, activity, sex, and diet were correlated with differences in alpha-diversity, with diversity decreasing in dogs consuming glucosamine. Beta-diversity analysis revealed clustering of dogs based on glucosamine supplementation status. Glucosamine supplementation and exercise-related activity were associated with greater inter-individual pairwise distances. At the family level, Lactobacillaceae and Anaerovoracaceae relative abundances were lower in supplemented dogs when activity was accounted for. At the genus level, Eubacterium [brachy], Sellimonus, Parvibacter, and an unclassified genus belonging to the same family as Parvibacter (Eggerthellaceae) all were lower in supplemented dogs, but only significantly so post-activity. Our findings suggest that glucosamine supplementation alters microbiome composition in sled dogs, particularly in the context of exercise-related activity.

Thiophene π-Bridge Manipulation of NIR-II AIEgens for Multimodal Tumor Phototheranostics.

The fabrication of a multimodal phototheranostic platform on the basis of single-component theranostic agent to afford both imaging and therapy simultaneously, is attractive yet full of challenges. The emergence of aggregation-induced emission luminogens (AIEgens), particularly those emit fluorescence in the second near-infrared window (NIR-II), provides a powerful tool for cancer treatment by virtue of adjustable pathway for radiative/non-radiative energy consumption, deeper penetration depth and aggregation-enhanced theranostic performance. Although bulky thiophene π-bridges such as ortho-alkylated thiophene, 3,4-ethoxylene dioxythiophene and benzo[c]thiophene are commonly adopted to construct NIR-II AIEgens, the subtle differentiation on their theranostic behaviours has yet to be comprehensively investigated. In this work, systematical investigations discovered that AIEgen BT-NS bearing benzo[c]thiophene possesses acceptable NIR-II fluorescence emission intensity, efficient reactive oxygen species generation, and high photothermal conversion efficiency. Eventually, by using of BT-NS nanoparticles, unprecedented performance on NIR-II fluorescence/photoacoustic/photothermal imaging-guided synergistic photodynamic/photothermal elimination of tumors was demonstrated. This study thus offers useful insights into developing versatile phototheranostic systems for clinical trials.

An NIR-II Excitable AIE Small Molecule with Multimodal Phototheranostic Features for Orthotopic Breast Cancer Treatment.

One-for-all phototheranostics, referring to a single component simultaneously exhibiting multiple optical imaging and therapeutic modalities, has attracted significant attention due to its excellent performance in cancer treatment. Benefitting from the superiority in balancing the diverse competing energy dissipation pathways, aggregation-induced emission luminogens (AIEgens) are proven to be ideal templates for constructing one-for-all multimodal phototheranostic agents. However, to this knowledge, the all-round AIEgens that can be triggered by a second near-infrared (NIR-II, 1000-1700 nm) light have not been reported. Given the deep tissue penetration and high maximum permissible exposure of the NIR-II excitation light, herein, this work reports for the first time an NIR-II laser excitable AIE small molecule (named BETT-2) with multimodal phototheranostic features by taking full use of the advantage of AIEgens in single molecule-facilitated versatility as well as synchronously maximizing the molecular donor-acceptor strength and conformational distortion. As formulated into nanoparticles (NPs), the high performance of BETT-2 NPs in NIR-II light-driven fluorescence-photoacoustic-photothermal trimodal imaging-guided photodynamic-photothermal synergistic therapy of orthotopic mouse breast tumors is fully demonstrated by the systematic in vitro and in vivo evaluations. This work offers valuable insights for developing NIR-II laser activatable one-for-all phototheranostic systems.

Multifunctional Nanoplatform for Single NIR Laser-Regulated Efficient PDT/PTT/Chemotherapy.

The combination of phototherapy and chemotherapy with superior advantages is a promising strategy for cancer therapy. However, combination therapy is generally regulated by two different wavelengths of light or other stimuli, which results in complex operations and inevitable systemic side effects, even affecting therapeutic efficacy. Herein, we design a signal NIR light-regulated nanoplatform via the self-assembly process of reactive oxygen species (ROS)-sensitive prodrug (DTD), human serum albumin (HSA), and IR780 for combined photothermal/photodynamic therapy and chemotherapy. Upon 808 nm laser irradiation, IR780 in nanoparticles generates abundant ROS and a significant photothermal effect to achieve photothermal/photodynamic therapy. Meanwhile, the generating ROS further cleans up the thioketal link to release DOX for chemotherapy. Hence, signal NIR light can effectively control the process of combination therapy. In vivo and in vitro experiment results demonstrate that the multifunctional nanoparticles exhibit excellent antitumor efficacy via the combination of phototherapy and chemotherapy controlled by a signal NIR laser. Overall, the signal NIR light-regulated nanoparticles with combination therapy performance provide a versatile platform for enhancing antitumor efficacy.

Facile fabrication of carbon nanotube hollow microspheres as a fiber coating for ultrasensitive solid-phase microextraction of phthalic acid esters in tea beverages.

The efficient extraction of phthalic acid esters (PAEs) is challenging due to their extremely low concentration, complicated matrices and hydrophilicity. Herein, hollow microspheres, as an ideal coating, possess significant potential for solid-phase microextraction (SPME) due to their fascinating properties. In this study, multiwalled carbon nanotube hollow microspheres (MWCNT-HMs) were utilized as a fiber coating for the SPME of PAEs from tea beverages. MWCNT-HMs were obtained by dissolving the polystyrene (PS) cores with organic solvents. Interestingly, MWCNT-HMs well maintain the morphology of the MWCNTs@PS precursors. The layer-by-layer (LBL) assembly of MWCNTs on PS microsphere templates was achieved through electrostatic interactions. Six PAEs, di-ethyl phthalate (DEP), di-iso-butyl phthalate (DIBP), di-n-butyl phthalate (DBP), benzyl butyl phthalate (BBP), di-2-ethylhexyl phthalate (DEHP) and di-n-octyl phthalate (DOP), were selected as target analytes for assessing the efficiency of the coating for SPME. The stirring rate, sample solution pH and extraction time were optimized by using the Box-Behnken design. Under optimal working conditions, the proposed MWCNT-HMs/SPME was coupled with gas chromatography-tandem mass spectrometry (GC-MS/MS) to achieve high enrichment factors (118-2137), wide linearity (0.0004-10 µg L-1), low limits of detection (0.00011-0.0026 µg L-1) and acceptable recovery (80.2-108.5%) for the detection of PAEs. Therefore, the MWCNT-HM coated fibers are promising alternatives in the SPME method for the sensitive detection of PAEs at trace levels in tea beverages.

Sodium humate ameliorates LPS-induced liver injury in mice by inhibiting TLR4/NF-κB and activating NRF2/HO-1 signaling pathways.

BACKGROUND: Acute liver damage is a type of liver disease that has a significant global occurrence and a lack of successful treatment and prevention approaches. Sodium humate (HNa), a natural organic substance, has extensive applications in traditional Chinese medicine due to its antibacterial, anti-diarrheal, and anti-inflammatory characteristics. The purpose of this research was to examine the mitigating impacts of HNa on liver damage induced by lipopolysaccharide (LPS) in mice. METHODS AND RESULTS: A total of 30 female mice were randomly assigned into Con, Mod, L-HNa, M-HNa, and H-HNa groups. Mice in the Con and Mod groups were gavaged with PBS, whereas L-HNa, M-HNa, and H-HNa groups mice were gavaged with 0.1%, 0.3%, and 0.5% HNa, daily. On day 21, Mod, L-HNa, M-HNa, and H-HNa groups mice were challenged with LPS (10 mg/kg). We discovered that pretreatment with HNa improved liver pathological damage and inflammation by inhibiting the toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling pathway, enhancing the polarization of liver M2 macrophages, and reducing the levels of inflammatory cytokines. Our further study found that pretreatment with HNa enhanced the liver ability to combat oxidative stress and reduced hepatocyte apoptosis by activating the nuclear factor erythroid-2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) signaling pathway and enhancing the activities of antioxidant enzymes. CONCLUSIONS: In conclusion, HNa could alleviate LPS-induced liver damage through inhibiting TLR4/NF-κB and activating NRF2/HO-1 signaling pathways. This study is the first to discover the therapeutic effects of HNa on liver damage induced by LPS.

Safe utilization of bioresources in gentamicin mycelial residues by thermal treatment: Antibiotic degradation, resistance gene inactivation and available nutrients promotion.

Gentamicin mycelium residues (GMRs) abundant in organic substances were generated during the production of gentamicin. Inappropriate handling techniques not only waste valuable resources, they could also result in residual gentamicin into the natural environment, leading to the generation of antibiotic resistance genes (ARGs), which would cause a significant threat to ecological system and human health. In the present work, the effects of thermal treatment on the removal of residual gentamicin in GMRs, as well as the changes of associated ARGs abundance, antimicrobial activity and bioresources properties were investigated. The results indicated that the hazards of GMRs was significantly reduced through thermal treatment. The degradation rate of residual gentamicin in GMRs reached 100 %, the total abundance of gentamicin resistance genes declined from 8.20 to 1.14 × 10-5 and the antibacterial activity of the decomposition products of GMRs on Vibrio fischeri was markedly reduced at 200 °C for 120 min. Additionally, the thermal treatment remarkably influenced the bioresource properties of GMRs-decomposition products. The release of soluble organic matters including soluble carbohydrates and soluble proteins have been enhanced in GMRs, while excessively high temperatures could lead to a reduction of nutrient substances. Generally, thermal treatment technology was a promising strategy for synergistic reducing hazards and utilizing bioresources of GMRs.

Effects of dietary astaxanthin on growth performance, muscle composition, non-specific immunity, gene expression, and ammonia resistance of juvenile ivory shell (Babylonia areolate).

Astaxanthin is one of the important immunopotentators in aquaculture. However, little is known about the physiological changes and stress resistance effects of astaxanthin in marine gastropods. In this study, the effects of different astaxanthin concentrations (0, 25, 50, 75, and 100 mg/kg) on the growth, muscle composition, immune function, and resistance to ammonia stress in Babylonia areolata were investigated after three months of rearing. With the increase in astaxanthin content, the weight gain rate (WGR), specific growth rate (SGR), and survival rate (SR) of B. areolata showed an increasing trend. The 75-100 mg/kg group was significantly higher than the control group (0 mg/kg). There was no significant difference in the flesh shell ratio (FSR), viscerosomatic index (VSI), and soft tissue index (STI) of the experimental groups. Astaxanthin (75 mg/kg) significantly increased muscle crude protein content and increased hepatopancreas alkaline phosphatase (AKP), superoxide dismutase (SOD), and catalase (CAT) activity. Astaxanthin (75-100 mg/kg) significantly increased the total antioxidant capacity (T-AOC) and acid phosphatase (ACP) of the hepatopancreas and decreased the malondialdehyde (MDA) content of B. areolata. Astaxanthin significantly induced the expression levels of functional genes, such as SOD, Cu/ZnSOD, ferritin, ACP, and CYC in hepatopancreas and increased the survival rate of B. areolata under ammonia stress. The addition of 75-100 mg/kg astaxanthin to the feed improved the growth performance, muscle composition, immune function, and resistance to ammonia stress of B. areolata.

Costunolide ameliorates angiotensin II-induced atrial inflammation and fibrosis by regulating mitochondrial function and oxidative stress in mice: A possible therapeutic approach for atrial fibrillation.

Atrial fibrillation (AF) is a cardiac disease characterized by disordered atrial electrical activity. Atrial inflammation and fibrosis are involved in AF progression. Costunolide (COS) is a sesquiterpene lactone containing anti-inflammatory and anti-fibrotic activities. This study aims to explore the underlying mechanisms by which COS protects against AF. Male C57BL/6 mice (8- to 10-week-old) were infused with angiotensin (Ang) II for 3 weeks. Meanwhile, different doses of COS (COS-L: 10 mg/kg, COS-H: 20 mg/kg) were administered to mice by intragastric treatment. The results showed irregular and rapid heart rates in Ang II-treated mice. Moreover, the levels of inflammatory cytokines and fibrotic factors were elevated in mice. COS triggered a reduction of Ang II-induced inflammation and fibrosis, which conferred a protective effect. Mechanistically, mitochondrial dysfunction with mitochondrial respiration inhibition and aberrant ATP levels were observed after Ang II treatment. Moreover, Ang-II-induced excessive reactive oxygen species caused oxidative stress, which was further aggravated by inhibiting Nrf2 nuclear translocation. Importantly, COS diminished these Ang-II-mediated effects in mice. In conclusion, COS attenuated inflammation and fibrosis in Ang-II-treated mice by alleviating mitochondrial dysfunction and oxidative stress. Our findings represent a potential therapeutic option for AF treatment.

Photo-Triggered Cascade Therapy: A NIR-II AIE Luminogen Collaborating with Nitric Oxide Facilitates Efficient Collagen Depletion for Boosting Pancreatic Cancer Phototheranostics.

The dense extracellular matrix (ECM) in the pancreatic cancer severely hampers the penetration of nanodrugs, which causes inferior therapeutic efficacy. To address this issue, a multifunctional liposome, namely, Lip-DTI/NO, integrating a type-I photosensitizer DTITBT with glutathione (GSH) or heat-responsive nitric oxide (NO) donor S-nitroso-N-acetyl-D-penicillamine (SNAP) is constructed to deplete the tumor ECM, leading to enhanced drug delivery and consequently improved phototherapy. The loaded DTITBT possesses multiple functions including NIR-II fluorescence imaging, efficient superoxide radical (O2 •-) generation and excellent photothermal conversion efficiency, making it feasible for precisely pinpointing the tumor in the phototherapy process. Responding to the intracellular overexpressed glutathione or heat produced by photothermal effect of DTITBT, NO can be released from SNAP. Upon 808 nm laser irradiation, Lip-DTI/NO could selectively induce in situ generation of peroxynitrite anion (ONOO-) in tumor after cascade processes including O2 •- production, GSH or heat-triggered NO release, and rapid reaction between O2 •- and NO. The generated ONOO- could activate the expression of endogenous matrix metalloproteinases which could efficiently digest collagen of tumor ECM, thus facilitating enhanced penetration and accumulation of Lip-DTI/NO in tumor. In vivo evaluation demonstrates the notable therapeutic efficacy via ONOO--potentiated synergistic photodynamic-photothermal therapies on both subcutaneous and orthotopic pancreatic cancer model.