Curcumin-mediated photodynamic treatment extends the shelf life of salmon (Salmo salar) sashimi during chilled storage: Comparisons of preservation effects with five natural preservatives.

The impact of curcumin-mediated photodynamic treatment (PDT) on the microbiological, physicochemical and sensory qualities of salmon sashimi has not been explored. Herein, this study aimed to evaluate the effects of PDT on the shelf-life quality of ready-to-eat salmon fillets during chilled storage (4 °C) in comparison with five widely investigated natural extracts, including cinnamic aldehyde, rosmarinic acid, chlorogenic acid, dihydromyricetin and nisin. From a microbial perspective, PDT exhibited outstanding bacterial inhibition, the results of total viable counts, total coliform bacteria, psychrotrophic bacteria, Pseudomonas spp., Enterobacteriaceae family, and H2S-producing bacteria were notably inactivated (p < 0.05) to meet the acceptable limits by PDT in comparison with those of the control group and natural origin groups, which could extend the shelf-life of salmon fillets from<6 days to 10 days. In the alteration of physicochemical indicators, PDT and natural extracts were able to maintain the pH value and retard lipid oxidation in salmon fillets, while apparently slowing the accumulation (p < 0.05) of total volatile basic nitrogen and biogenic amines, especially the allergen histamine, which contrary to with the variation trend of spoilage microbiota. In parallel, PDT worked effectively (p < 0.05) on the breakdown of adenosine triphosphate and adenosine diphosphate to maintain salmon fillet freshness. Additionally, the physical indicators of texture profile and color did not have obvious changes (p < 0.05) after treated by PDT during the shelf life. Besides, the sensory scores of salmon samples were also significantly improved. In general, PDT not only has a positive effect on organoleptic indicators but is also a potential antimicrobial strategy for improving the quality of salmon sashimi.

An adverse outcome pathway-based approach to assess aurantio-obtusin-induced hepatotoxicity.

Cassiae semen (CS), a traditional Chinese medicine, has various bioactivities in preclinical and clinical practice. Aurantio-obtusin (AO) is a major anthraquinone (AQ) ingredient derived from CS, and has drawn public concerns over its potential hepatotoxicity. We previously found that AO induces hepatic necroinflammation by activating NOD-like receptor protein 3 inflammasome signaling. However, the mechanisms contributing to AO-motivated hepatotoxicity remain unclear. Herein, we evaluated hepatotoxic effects of AO on three liver cell lines by molecular and biochemical analyses. We found that AO caused cell viability inhibition and biochemistry dysfunction in the liver cells. Furthermore, AO elevated reactive oxygen species (ROS), followed by mitochondrial dysfunction (decreases in mitochondrial membrane potential and adenosine triphosphate) and apoptosis (increased Caspase-3, Cleaved caspase-3, Cytochrome c and Bax expression, and decreased Bcl-2 expression). We also found that AO increased the lipid peroxidation (LPO) and enhanced ferroptosis by activating cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element-binding (CREB) pathway (increases in PKA, p-CREB, acyl-CoA synthetase long chain family member 4). Based on these results, we used an AOP framework to explore the mechanisms underlying AO's hepatotoxicity. It starts from molecular initiating event (ROS), and follows two critical toxicity pathways (i.e., mitochondrial dysfunction-mediated apoptosis and LPO-enhanced ferroptosis) over a series of key events (KEs) to the adverse outcome of hepatotoxicity. The results of an assessment confidence in the adverse outcome pathway (AOP) framework supported the evidence concordance in dose-response, temporal and incidence relationships between KEs in AO-induced hepatotoxicity. This study's findings offer a novel toxicity pathway network for AO-caused hepatotoxicity.

Aurantio-obtusin induces hepatotoxicity through activation of NLRP3 inflammasome signaling.

Aurantio-obtusin (AO) is a major anthraquinone (AQ) compound derived from Cassiae semen (CS). Although pharmacological studies have shown that the CS extracts can serve as effective agents in preclinical and clinical practice, AQ-induced hepatotoxicity in humans has attracted widespread attention. To explore whether AO induces hepatotoxicity and its underlying mechanisms, we exposed larval zebrafish and mice to AO. We found that AO delayed yolk sac absorption, and increased liver area and inflammation in the larval zebrafish. This inflammation was manifested as an increase in liver neutrophils and the up-regulated mRNA expression of interleukin-6 (Il-6) and tumor necrosis factor-α (Tnf-α) in the larval zebrafish. Furthermore, a pharmacokinetics study showed that AO was quickly absorbed into the blood and rapidly metabolized in the mice. Of note, AO induced hepatotoxicity in a gender-dependent manner, characterized by liver dysfunction, increased hepatocyte necrosis with inflammatory infiltration, and up-regulated mRNAs of Il-6, Tnf-α and monocyte chemotactic protein 1(Mcp1) in the female mice after 28-day oral administration. It also highlighted that AO triggered NOD-like receptor protein (NLRP) signaling in the female mice, as evidenced by the increased NLRP3, Caspase-1, pro-IL-1ß, IL-1ß and IL-18. Finally, we found that AO led to a significant increase in potassium calcium-activated channel, subfamily N, member 4 (KCNN4) and reactive oxygen species (ROS) levels, along with decreased nuclear factor kappa B p65 (NF-κB p65), in the female mouse livers. In conclusion, AO induced hepatotoxicity by activating NLRP3 inflammasome signaling, at least in part, through increased KCNN4 and ROS production, and NF-κB inhibition.

An aqueous extract of Prunella vulgaris L. inhibits the growth of papillary thyroid carcinoma by inducing autophagy in vivo and in vitro.

The continued global rise in papillary thyroid carcinoma (PTC) combined with potential adverse effects of regular treatments calls for an alternative therapy. Prunella vulgaris L. (PV) is commonly used as a herbal remedy for thyroid diseases in China, but its influence on PTC is unclear. This study investigated the effect of PV aqueous extract on PTC and its underlying mechanism using a mouse xenograft model and the human PTC cell line K1. PV suppressed tumor growth in PTC-bearing mice at 0.05 and 0.1 g/kg bw, accompanied by improvements in autophagy-related protein expressions in xenografts. In K1 cells, PV inhibited cell growth and induced autophagic flux, manifesting as changes in autophagy-related proteins, the presence of autophagosomes, and a further increase in LC3-II by co-incubation with bafilomycin A1. Autophagy inhibitor 3-methyladenine ameliorated the autophagic cell death caused by PV. The mammalian target of rapamycin (mTOR) activator MHY1485 blocked the antiproliferative activity of PV by regulating mTOR, unc-51-like autophagy activating kinase 1 (ULK1), autophagosomes formation, and autophagy-related proteins. The adenosine monophosphate-activated protein kinase (AMPK) inhibitor compound C attenuated PV-induced inhibition of mTOR. Our results suggest that PV inhibits the growth of PTC in vivo and in vitro via autophagy, which is associated with the AMPK/mTOR/ULK1 pathway. Thus, PV has the potential to function as a therapeutic agent against PTC.

Associations of regular glucosamine use with all-cause and cause-specific mortality: a large prospective cohort study.

OBJECTIVES: To evaluate the associations of regular glucosamine use with all-cause and cause-specific mortality in a large prospective cohort. METHODS: This population-based prospective cohort study included 495 077 women and men (mean (SD) age, 56.6 (8.1) years) from the UK Biobank study. Participants were recruited from 2006 to 2010 and were followed up through 2018. We evaluated all-cause mortality and mortality due to cardiovascular disease (CVD), cancer, respiratory and digestive disease. HRs and 95% CIs for all-cause and cause-specific mortality were calculated using Cox proportional hazards models with adjustment for potential confounding variables. RESULTS: At baseline, 19.1% of the participants reported regular use of glucosamine supplements. During a median follow-up of 8.9 years (IQR 8.3-9.7 years), 19 882 all-cause deaths were recorded, including 3802 CVD deaths, 8090 cancer deaths, 3380 respiratory disease deaths and 1061 digestive disease deaths. In multivariable adjusted analyses, the HRs associated with glucosamine use were 0.85 (95% CI 0.82 to 0.89) for all-cause mortality, 0.82 (95% CI 0.74 to 0.90) for CVD mortality, 0.94 (95% CI 0.88 to 0.99) for cancer mortality, 0.73 (95% CI 0.66 to 0.81) for respiratory mortality and 0.74 (95% CI 0.62 to 0.90) for digestive mortality. The inverse associations of glucosamine use with all-cause mortality seemed to be somewhat stronger among current than non-current smokers (p for interaction=0.00080). CONCLUSIONS: Regular glucosamine supplementation was associated with lower mortality due to all causes, cancer, CVD, respiratory and digestive diseases.

Effects of Prunella vulgaris on the mice immune function.

The present study was designed to evaluate the effects of Prunella Vulgaris (P. vulgaris) on the immune function in mice. The mice were randomly divided into one control group and three treatment groups of 10 mice each. The control group received pure water and the treatment groups received P. vulgaris extract at concentrations of 0.15, 0.30 and 0.90 g/kg BW orally for 30 days, respectively. Changes in cell immune function, non-specific immunity and humoral immunity function were evaluated. Active lymphocytes and T lymphocyte subsets were determined by fluorescence-activated cell sorting (FACS). Certain Serum concentrations of cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that, for cell immune function, compared with the control group, foot pad thickness in high dose group increased significantly (p<0.01), whereas no significant difference in the proliferative ability of splenic lymphocytes was observed among all groups (p>0.05). For non-specific immunity, NK cell activity increased significantly in a dose-dependent manner in P. vulgaris treated mice (p<0.01), mononuclear-macrophage function in medium and high dose P. vulgaris treated mice were significantly higher than that of the control group (p<0.05). For humoral immunity, no significant differences were observed in terms of the half value of hemolysis (HC50), number of hemolytic plaques and serum IgG level (p>0.05). The percentage of active T and Th lymphocytes of mice peripheral blood in high dose group were significantly higher than that of the control group (p<0.01). There was no significant difference in serum levels of IL-1ß, IL-4, IL-10 and IFN-γ among all of the four groups (p>0.05). The data indicated that 0.90 g/kg BW P. vulgaris extract (equivalent to 7.5 g/kg BW crude drug) had some effect on cellular immune function and non-specific immune function in mice.

[Effects of jing'an capsule on rat sperm quality].

OBJECTIVE: The effects of Jing'an capsule on the quality of rat sperm were studied to supply data for its safe clinical use. METHODS: Eighty SD male rats were evenly and randomly divided into three test groups and one control group. Then the test groups were continuously given Jing'an capsule at different dosages: 557.1 mg/kg, 5,571 mg/kg or 11,420 mg/kg and the control group was given starch (20 g/L). Sixty days later, one of the epididymides, the sperm density was made and the sperm motility and morphology were investigated. The data obtained were analyzed by ANOVA, chi 2 test and Kruskal-Wallis test. RESULTS: The sperm density, motility and morphology were variable at different dosages. Compared with the control, the sperm density increased significantly at the dosage of 557.1 mg/kg(P < 0.05), and a significant decrease was observed in the sperm density and motility (P < 0.05) at the dosage of 11,420 mg/kg. Although the rate of abnormal sperm morphology decreased at the dosage of 557.1 mg/kg and increased at the dosage of 5,571 mg/kg or 11,420 mg/kg compared with the control, there was no statistic significance(P < 0.05). CONCLUSIONS: A low dosage of Jing'an capsule might ameliorate the quality of sperm, while a high dosage could do damage to sperm.

[Effect of zinc on reproductive toxicity in rats].

The purpose of this study was to explore the effect of zinc on reproductive function in rats. The results revealed that the sperm count, sperm motility and reproductive function appeared to be enhanced in male rats by 60 days successive administration of low dose zinc (12 mg/kg) or medium dose zinc (120 mg/kg), whereas reproductive system damages characterized by lowering of reproductive function would be resulted by high dose zinc(240 mg/kg). However, no effect on the growth and development of the second generation was shown, suggesting that the injury was just limited to certain extent.