Metabolomics and metatranscriptomics reveal the influence mechanism of endogenous microbe (Staphylococcus succinus) inoculation on the flavor of fermented chili pepper.

This study integrated metabolomic and metatranscriptomic techniques to examine how the endogenous microbe, Staphylococcus succinus, influenced the essential flavor of fermented chili peppers. The mechanisms governing spontaneous fermentation and S. succinus-inoculated fermentation were also elucidated. Esters (e.g., ethyl undecanoate, isoamyl acetate, and methyl salicylate), terpenes (e.g., terpinen-4-ol), and alcohols (e.g., α-terpineol, linalool, and 4-methyl-3-heptanol) were found to be the key aroma-active compounds, aspartic acid (Asp) and glutamic acid (Glu) were identified as primary flavoring free amino acids. Notably, during the early stages of S. succinus-inoculated fermentation, the production of these essential metabolites was abundant, while their gradual increase over time was observed in the case of spontaneous fermentation. Metatranscriptomic analysis revealed that S. succinus inoculation could up-regulate genes related to glycolysis, amino acid metabolism, and aroma compound synthesis. These changes sequentially boosted the production of sweet and umami free amino acids, enhanced organic acid levels, increased unique aroma compound generation, and further improved the flavor and quality of the fermented chili peppers. Therefore, S. succinus inoculation can augment the sensory quality of fermented chili peppers, making this strain a promising candidate for Sichuan pickle fermentation starters.

Serum Expression Level of MicroRNA-122 and Its Significance in Patients with Hepatitis B Virus Infection.

OBJECTIVES: To analyze the expression of miR-122 and evaluate its significance in patients with HBV infection in different phases. METHODS: Eleven chronic hepatitis B (CHB), 26 hepatitis B virus (HBV)-induced cirrhosis, 16 HBV-associated hepatocellular carcinoma (HCC) patients and 10 healthy control cases were enrolled. The serum levels of miR-122 were detected by RT-PCR and compared between healthy individuals and CHB at different stages. RESULTS: Compared with healthy control cases, serum miR-122 levels were markedly increased in HBV infection cases (AUC = 0.795, P=0.002). In the CHB group, miR-122 levels were positively associated with albumin levels (P < 0.05) but had no significant associations with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (P > 0.05). In the cirrhosis group, miR-122 expression was remarkably lower in the Child C group in comparison with the Child A group (P=0.025). At the same time, miR-122 amounts had a negative correlation with HVPG (P < 0.05). In the HCC group, miR-122 amounts were negatively associated with alkaline phosphatase (AKP) and alpha-fetoprotein (AFP) (P < 0.05). Serum miR-122 amounts in 3 patients who died were lower than the survival group (5.520 ± 0.522 vs. 5.860 ± 1.183, P > 0.05). CONCLUSION: Serum miR-122 can be leveraged to screen patients with HBV infection. In HBV sufferers, the serum miR-122 expression level is related to liver disease progression, hence making it an underlying molecular biomarker for predicting the development of CHB.

LINC00665 Targets miR-214-3p/MAPK1 Axis to Accelerate Hepatocellular Carcinoma Growth and Warburg Effect.

Inhibition of aerobic glycolysis is a hopeful method for cancer treatment. In this study, we aimed to explore LINC00665/miR-214-3p/MAPK1 role in regulating cell viability and aerobic glycolysis in hepatocellular carcinoma (HCC). The expressions of LINC00665 in 50 paired HCC tissues and normal tissues were determined by qRT-PCR. Pearson analysis was applied to evaluate the association between the expression levels of miR-214-3p, LINC00665, and MAPK1 in HCC tissues. The interactions between miR-214-3p and LINC00665 or MAPK1 were determined by luciferase reporter assay and RNA immunoprecipitation. CCK-8 and colony formation assays were used for cell viability evaluation. Lactate production, glucose consumption, and ATP levels were measured to assess Warburg effect. The results showed that LINC00665 was overexpressed in HCC, which positively associated with MAPK1 level and negatively associated with miR-214-3p level in HCC tissues. Overexpression of LINC00665 led to significant enhancements in cell viability and colony formation, whereas this effect was weakened when miR-214-3p was overexpressed or MAPK1 was downregulated. In addition, deletion of LINC00665 expression repressed tumor formation in vivo. Mechanically, LINC00665 increased MAPK1 expression through binding to miR-214-3p. Collectively, this study revealed that LINC00665 accelerated cell growth and Warburg effect through sponging miR-214-3p to increase MAPK1 expression in HCC.

Pioglitazone, a PPAR-γ activator, attenuates the severity of cerulein-induced acute pancreatitis by modulating early growth response-1 transcription factor.

The purpose of this study was to test the hypothesis that activation of endogenous peroxisome proliferator-activated receptor (PPARγ) inhibits induction of early growth response factor-1 (Egr-1), which is rapidly induced in the pancreas following cerulein intraperitoneal injection. Acute pancreatitis was induced in mice by hourly intraperitoneal injection of cerulein. Pioglitazone was administered prophylactically and pancreatic inflammation was assessed. AR42J cells were stimulated with caerulein 10⁻8 M co-incubated in presence of different concentration of pioglitazone. The expression of PPARγ, Egr-1, and the target genes of Egr-1 were studied by real-time reverse transcriptase polymerase chain reaction (PCR), Western blot, and immunohistochemistry. In vitro, a PPAR-γ activator (pioglitazone) strikingly diminished Egr-1 mRNA and protein expression corresponding to Egr-1. In vivo, treatment with pioglitazone prior to the intraperitoneal injection of cerulein induction of Egr-1 and its target genes such as, monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1). The inhibitory effect of pioglitazone on Egr-1 expression induced by cerulein was almost fully restored by GW9662. Activation of PPAR-γ suppressed the activation of Egr-1 and its inflammatory gene targets and provided potent protection against pancreas injury. These data suggest a new mechanism in which PPAR-γ activation may decrease tissue inflammation in response to a cerulein insult.

Effects of antidepressive treatment of Saint John's wort extract related to autonomic nervous function in women with irritable bowel syndrome.

BACKGROUND AND AIM: Irritable bowel syndrome (IBS) patients usually manifest autonomic nerve dysfunctions and abnormal psychological behaviors. This study was to assess autonomic nervous system (ANS) response to different stressor as well as evaluate effects of antidepressive treatment of Saint John's Wort Extract in women with IBS. METHOD: Thirty women with IBS and 20 healthy women underwent serial ANS function tests. Five-minute-short-time heart rate variability (HRV) spectral analysis were assessed at a stress or resting recording period. Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) were used to measure their anxiety and depression conditions. After 8-weeks' antidepressant treatment, groups of IBS repeated the tests above. Subjects also completed a GI symptom diary once daily during the 2 weeks before therapy and for 2 weeks in the last scheduled therapy session. RESULTS: IBS-group showed a higher score in HAMA and HAMD (p < 0.01) and showed a significant increase in the low frequency band/high frequency band ratio (L/H) during the period in different stimuli (p <0.01), which was significantly different from controls. After 8-weeks' antidepressive treatment, L/H showed a significant decrease (p < 0.05) response to different stressor, which was significantly different from pre-treatment. Gastrointestinal (GI) symptoms of IBS were also relieved significantly. CONCLUSIONS: Antidepressive treatment can improve the conditions of psychology and the ANS reactivity to stress in patients with IBS.

Pioglitazone, a PPARgamma ligand, suppresses NFkappaB activation through inhibition of IkappaB kinase activation in cerulein-treated AR42J cells.

BACKGROUND AND AIM: NFkappaB plays a major role in the immune and inflammation responses of pancreatitis. Recently, there is increasing evidence that the expression and activity of PPARgamma may participate in the activity of NFkappaB. Therefore, we investigated a putative relationship of the two transcription factors in cerulein-treated pancreatic acinar AR42J cells. METHOD: AR42J were stimulated by cerulein with or without the presence of a PPARgamma activator pioglitazone or a PPARgamma antagonist GW9662. RESULTS: Treatment of AR42J cells with pioglitazone attenuated cerulein induced p50 and p65 NFkappaB dimer activity in the nucleus as measured by transcription factor assay. Cytosolic expression of IkappaBalpha protein was reduced by cerulein, basal signalling was not influenced by the PPARgamma inhibitor GW9662 and pioglitazone. Adversely, the inhibitory effect of pioglitazone on NFkappaB activity induced by cerulein was almost reversed by GW9662. CONCLUSION: These findings provide evidence for the involvement of the nuclear hormone receptors PPARgamma in the activity of NFkappaB in cerulein-treated AR42J cells.