The antivirulence activity, transcriptomics of EGCG and its protective effects on zebrafish infected by Aeromonas hydrophila

BackgroundAeromonas hydrophila is an important pathogen that mainly harms aquatic animals and exhibits resistance to a variety of antibiotics. This study investigated the effect of epigallocatechin-3-gallate (EGCG) on the virulence factors of A.hydrophila and its impact on adhesion, invasion, and cytotoxicity in Caco-2 cells. The potential mechanism of antibacterial activity of EGCG was investigated by transcriptomic analysis.ResultsEGCG not only inhibited the production of biofilm, hemolytic activity, motility, and protease activity of A.hydrophila, but also reduced its adhesion, invasion, and cytotoxicity in Caco-2 cells. Transcriptomic analysis indicated that the antimicrobial activity of EGCG may be achieved by weakening the chemotaxis and stress response of the bacteria, as well as inhibiting the TonB system. Animal studies demonstrated that EGCG can significantly improve the survival rate and organs damage of zebrafish infected with A.hydrophila.ConclusionEGCG would be a potential alternative drug for the prevention and treatment of A. hydrophila infections by anti-virulence mechanism

Apatinib combined with camrelizumab in the treatment of recurrent/metastatic nasopharyngeal carcinoma: a prospective multicenter phase II study

BackgroundPreclinical studies demonstrated that immune checkpoint inhibitors combined with antiangiogenic drugs have a synergistic anti-tumor effect. This present phase II trial aimed to evaluate the efficacy and safety of apatinib combined with camrelizumab in patients with recurrent/metastatic nasopharyngeal carcinoma (RM-NPC).MethodsPatients with RM-NPC were administered with apatinib at 250 mg orally once every day and with camrelizumab at 200 mg via intravenous infusion every 2 weeks until the disease progressed or toxicity became unacceptable. The objective response rate (ORR) was the primary endpoint, assessed using RECIST version 1.1. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety were the key secondary endpoints. This study was registered with ClinicalTrials.gov, NCT04350190.ResultsThis study enrolled 26 patients with RM-NPC between January 14, 2021 and September 15, 2021. At data cutoff (March 31, 2023), the median duration of follow-up was 16 months (ranging from 1 to 26 months). The ORR was 38.5% (10/26), the disease control rate (DCR) was 61.5% (16/26), and the median PFS was 6 months (IQR 3.0-20.0). The median OS was 14 months (IQR 6.0-21.25). Treatment-related grade 3 or 4 adverse events occurred in seven (26.9%) patients, and comprised anemia (7.7%), stomatitis (3.8%), headache (3.8%), pneumonia (7.7%), and myocarditis (3.8%). There were no serious treatment-related adverse events or treatment-related deaths.ConclusionIn patients with RM-NPC, apatinib plus camrelizumab showed promising antitumor activity and manageable toxicities

Compost bacteria provide antifungal activity against grey mold and Alternaria rot on bell pepper fruit

Bell pepper (Capsicum annuum L.) fruit are susceptible to various molds, including grey mold and Alternaria rot. In this work, antagonistic bacteria isolated from disease-suppressive composts were assessed for their ability to reduce the mycelial growth of Botrytis cinerea Persoon and Alternaria alternata (Fries) Keissler as well as to suppress grey mold and Alternaria rot on bell pepper. Results showed that different bacterial antagonists reduced mycelial growth of B. cinerea and A. alternata by up to 49% and 53%, respectively. The bacteria provided inhibition of grey mold, reducing incidence and severity by as much as 43% and 67%, respectively. The isolates also provided strong inhibitory effects against Alternaria rot, decreasing incidence and severity by as much as 77% and 80%, respectively. Pseudomonas and Arthrobacter spp. were particularly suppressive to Alternaria rot. Results of this study suggest antagonistic bacteria may represent a potential method for controlling fruit rot of bell pepper

The Antiaging Activities of Phytochemicals in Dark-Colored Plant Foods: Involvement of the Autophagy- and Apoptosis-Associated Pathways

In the last two decades, human life expectancy has increased by about 10 years, but this has not been accompanied by a corresponding increase in healthy lifespan. Aging is associated with a wide range of human disorders, including cancer, diabetes, and cardiovascular and neurodegenerative diseases. Delaying the aging of organs or tissues and improving the physiological functions of the elderly can reduce the risk of aging-related diseases. Autophagy and apoptosis are crucial mechanisms for cell survival and tissue homeostasis, and may also be primary aging-regulatory pathways. Recent epidemiological studies have shown that eating more colorful plant foods could increase life expectancy. Several representative phytochemicals in dark-colored plant foods such as quercetin, catechin, curcumin, anthocyanins, and lycopene have apparent antiaging potential. Nevertheless, the antiaging signaling pathways of the phytochemicals from dark-colored plant foods remain elusive. In the present review, we summarized autophagy- and apoptosis-associated targeting pathways of those phytochemicals and discussed the core targets involved in the antiaging effects. Further clinical evaluation and exploitation of phytochemicals as antiaging agents are needed to develop novel antiaging therapeutics for preventing age-related diseases and improving a healthy lifespan

Silibinin ameliorates deoxycholic acid-induced pyroptosis in steatotic HepG2 cells by inhibiting NLRP3 inflammasome activation

Nonalcoholic steatohepatitis (NASH) represents an inflammatory subtype of nonalcoholic fatty liver disease (NAFLD). The activation of the NOD-like receptor protein 3 (NLRP3) inflammasome triggers pyroptosis, thus propelling the progression from simple steatosis to NASH. Silibinin, a hepatoprotective compound derived from milk thistle, exerts diverse hepatoprotective effects. However, the direct impact of silibinin on NLRP3 inflammasome activation and its ability to mitigate pyroptosis remain uncertain. To address this, we utilized an in vitro model of NASH, employing HepG2 cells treated with deoxycholic acid (DCA) and free fatty acids. Subsequently, we treated these model cells with silibinin for 24 h. Our findings demonstrated that, although there were no significant changes in cellular lipid content, silibinin effectively ameliorated hepatocyte injuries. Silibinin treatment inhibited the activation of the NLRP3 inflammasome and suppressed DCA-induced pyroptosis. Additionally, molecular docking analysis revealed that silibinin exhibited a binding affinity to components of the NLRP3 inflammasome similar to that of MCC950, a selective NLRP3 inhibitor. These results suggest that silibinin may alleviate inflammation in DCA-exposed HepG2 cells by mitigating pyroptosis, possibly through its binding affinity and inhibition of the NLRP3 inflammasome. Overall, our study indicates that silibinin holds promise as a therapeutic agent for NASH by modulating pyroptosis and inhibiting NLRP3 inflammasome activation

Table_1_The antivirulence activity, transcriptomics of EGCG and its protective effects on zebrafish infected by Aeromonas hydrophila.docx

BackgroundAeromonas hydrophila is an important pathogen that mainly harms aquatic animals and exhibits resistance to a variety of antibiotics. This study investigated the effect of epigallocatechin-3-gallate (EGCG) on the virulence factors of A.hydrophila and its impact on adhesion, invasion, and cytotoxicity in Caco-2 cells. The potential mechanism of antibacterial activity of EGCG was investigated by transcriptomic analysis.ResultsEGCG not only inhibited the production of biofilm, hemolytic activity, motility, and protease activity of A.hydrophila, but also reduced its adhesion, invasion, and cytotoxicity in Caco-2 cells. Transcriptomic analysis indicated that the antimicrobial activity of EGCG may be achieved by weakening the chemotaxis and stress response of the bacteria, as well as inhibiting the TonB system. Animal studies demonstrated that EGCG can significantly improve the survival rate and organs damage of zebrafish infected with A.hydrophila.ConclusionEGCG would be a potential alternative drug for the prevention and treatment of A. hydrophila infections by anti-virulence mechanism.</p