Modified Lichong decoction intervenes in colorectal cancer by modulating the intestinal flora and the Wnt/ß-catenin signaling pathway.

BACKGROUND: The pathogenesis and treatment of colorectal cancer (CRC) continue to be areas of ongoing research, especially the benefits of traditional Chinese medicine (TCM) in slowing the progression of CRC. This study was conducted to investigate the effectiveness and mechanism of action of modified Lichong decoction (MLCD) in inhibiting CRC progression. METHODS: We established CRC animal models using azoxymethane/dextran sodium sulfate (AOM/DSS) and administered high, medium, or low doses of MLCD or mesalazine (MS) for 9 weeks to observe MLCD alleviation of CRC. The optimal MLCD dose group was then subjected to metagenomic and RNA sequencing (RNA-seq) to explore the differentially abundant flora and genes in the control, model and MLCD groups. Finally, the mechanism of action was verified using WB, qRT‒PCR, immunohistochemistry and TUNEL staining. RESULTS: MLCD inhibited the progression of CRC, and the optimal effect was observed at high doses. MLCD regulated the structure and function of the intestinal flora by decreasing the abundance of harmful bacteria and increasing that of beneficial bacteria. The differentially expressed genes were mainly associated with the Wnt/ß-catenin pathway and the cell cycle. Molecular biology analysis indicated that MLCD suppressed the Wnt/ß-catenin pathway and the epithelial-mesenchymal transition (EMT), inhibited abnormal cell proliferation and promoted intestinal epithelial cell apoptosis. CONCLUSION: MLCD mitigated the abnormal growth of intestinal epithelial cells and promoted apoptosis, thereby inhibiting the progression of CRC. This inhibition was accomplished by modifying the intestinal microbiota and disrupting the Wnt/ß-catenin pathway and the EMT. Therefore, MLCD could serve as a potential component of TCM prescriptions for CRC treatment.

Effects of dietary Clostridium butyricum on the growth performance, digestion, and intestinal health of spotted sea bass (Lateolabrax maculatus).

Clostridium butyricum (CB) is known to promote growth, enhance immunity, promote digestion, and improve intestinal health. In this study, we investigated the effects of CB in the feed on growth performance, digestion, and intestinal health of juvenile spotted sea bass. To provide a theoretical basis for the development and application of CB in the feed of spotted sea bass, a total of 450 spotted sea bass with an initial body weight of (9.58 ± 0.05) g were randomly divided into six groups. Gradient levels with 0, 0.1%, 0.2%, 0.3%, 0.4%, and 0.5% of CB (1×109 cfu/g) were supplemented into diets, designated as CC, CB1, CB2, CB3, CB4, and CB5, respectively. Each group was fed for 54 days. Our results suggest that dietary 0.2% and 0.3% of CB can significantly increase the weight gain (WG) and specific growth rate (SGR) of spotted sea bass. The addition of CB significantly increased intestinal amylase activity, intestinal villus length, intestinal villus width, and intestinal muscle thickness. Similarly, CB supplementation increased the expression of tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8). Sequence analysis of the bacterial 16S rDNA region showed that dietary CB altered the intestinal microbiota profile of juvenile spotted sea bass, increasing the dominant bacteria in the intestine and decreasing the harmful bacteria. Overall, dietary addition of CB can improve growth performance, enhance intestinal immunity, improve intestinal flora structure, and comprehensively improve the health of spotted sea bass.

Paeoniflorin promotes intestinal stem cell-mediated epithelial regeneration and repair via PI3K-AKT-mTOR signalling in ulcerative colitis.

Ulcerative colitis (UC) is a chronic and immune-mediated inflammatory disorder characterized by abdominal pain, diarrhoea, and haematochezia. The goal of clinical therapy for UC is mucosal healing, accomplished by regenerating and repairing the intestinal epithelium. Paeoniflorin (PF) is a natural ingredient extracted from Paeonia lactiflora that has significant anti-inflammatory and immunoregulatory efficacy. In this study, we investigated how PF could regulate the renewal and differentiation of intestinal stem cells (ISCs) to improve the regeneration and repair of the intestinal epithelium in UC. Our experimental results showed that PF significantly alleviated colitis induced by dextran sulfate sodium (DSS) and ameliorated intestinal mucosal injury by regulating the renewal and differentiation of ISCs. The mechanism by which PF regulates ISCs was confirmed to be through PI3K-AKT-mTOR signalling. In vitro, we found that PF not only improved the growth of TNF-α-induced colon organoids but also increased the expression of genes and proteins related to the differentiation and regeneration of ISCs. Furthermore, PF promoted the repair ability of lipopolysaccharide (LPS)-induced IEC-6 cells. The mechanism by which PF regulates ISCs was further confirmed and was consistent with the in vivo results. Overall, these findings demonstrate that PF accelerates epithelial regeneration and repair by promoting the renewal and differentiation of ISCs, suggesting that PF treatment may be beneficial to mucosal healing in UC patients.

Comparison between outcomes of IgA nephropathy with nephrotic-range proteinuria and nephrotic syndrome: do podocytes play a role?

BACKGROUND: Nephrotic syndrome (NS) and nephrotic-range proteinuria (NRP) are uncommon in IgA nephropathy (IgAN), and their clinicopathology and prognosis have not been discussed. Podocytes may play an important role in both clinical phenotypes. METHODS: We investigated 119 biopsy-proven IgAN patients with proteinuria over 2 g/d. The patients were divided into three groups according to proteinuria level: the overt proteinuria (OP) group, NS group, and NRP group. In addition, according to the severity of foot process effacement (FPE), the patients were divided into three groups: the segmental FPE (SFPE) group, moderate FPE (MFPE) group, and diffuse FPE (DFPE) group. The outcome was survival from a combined event defined by a doubling of the baseline serum creatinine and a 50% reduction in eGFR or ESRD. RESULTS: Compared with the NRP group, patients in the NS group had more severe microscopic hematuria, presented with more severe endocapillary hypercellularity and had a higher percentage of DFPE. The Kaplan-Meier curve showed that MFPE patients had a better outcome in the NRP group <50% of tubular atrophy/interstitial fibrosis. In the multivariate model, the NRP group (HR = 17.098, 95% CI = 3.835-76.224) was associated with an increased risk of the combined event, while MFPE (HR = 0.260, 95% CI = 0.078-0.864; p = 0.028) was associated with a reduced risk of the combined event. After the addition of renin-angiotensin system inhibitors (RASi), the incidence of the combined event in the MFPE group (HR = 0.179, 95% CI = 0.047-0.689; p = 0.012) was further reduced. CONCLUSIONS: NS presented more active lesions and more severe FPE in IgAN. NRP was an independent risk factor for progression to the renal endpoint, while MFPE indicated a better prognosis in NRP without obvious chronic renal lesions, which may benefit from RASi.

p53 induces miR-199a-3p to suppress mechanistic target of rapamycin activation in cisplatin-induced acute kidney injury.

How p53 participates in acute kidney injury (AKI) progress and what are the underlying mechanisms remain illusive. For this issue, it is important to probe into the role of p53 in cisplatin-induced AKI. We find that p53 was upregulated in cisplatin-induced AKI, yet, pifithrin-α inhibites the p53 expression to attenuated renal injury and cell apoptosis both in vivo cisplatin-induced AKI mice and in vitro HK-2 human renal tubular epithelial cells. To knock down p53 by siRNA significantly decreased the miRNA, miR-199a-3p, expression in HK-2 cells. Blockade of miR-199a-3p significantly reduced cisplatin-induced cell apoptosis and inhibited caspase-3 activity. Mechanistically, we identified that miR-199a-3p directly bound to mechanistic target of rapamycin (mTOR) 3'-untranslated region and overexpressed miR-199a-3p reduce the expression and phosphorylation of mTOR. Furthermore, we demonstrated that p53 inhibited mTOR activation through activating miR-199a-3p. In conclusion, our findings reveal that p53, upregulating the expression of miR-199a-3p affects the progress of cisplatin-induced AKI, which might provide a promising therapeutic target of AKI.

Effective adsorption of phosphate from wastewaters by big composite pellets made of reduced steel slag and iron ore concentrate.

In order to remove phosphate from wastewater, a large plastic adsorption column filled with big phosphate-adsorbing pellets with diameters of 10 mm, heated by electromagnetic induction coils, was conceived. It was found that the prepared big pellets, which were made of reduced steel slag and iron ore concentrate, contain magnetic Fe and Fe3O4. The thermodynamics and kinetics of adsorption of phosphate from synthetic wastewaters on the pellets were studied in this work. The phosphate adsorption on the pellets followed three models of Freundlich, Langmuir and Dubinin-Kaganer-Radushkevick. The maximum phosphate adsorption capacity Qmax of the pellets were 2.46, 2.74 and 2.77 mg/g for the three temperatures of 20°C, 30°C and 40°C, respectively, based on the Langmuir model. The apparent adsorption energies were -12.9 kJ/mol for the three temperatures. It implied that ion exchange was the main mechanism involved in the adsorption processes. The adsorbed phosphate existed on the pellet surface mainly in the form of Fe3(PO4)2. A reduction pre-treatment of the pellet precursor with H2 greatly enhanced pellet adsorption for phosphate. The adsorption kinetics is better represented by a pseudo-first-order model. The adsorbed phosphate amounts were similar for both real and synthetic wastewaters under similar adsorption conditions. The percentage of adsorbed phosphate for a real wastewater increased with increasing pellet concentration and reached 99.2% at a pellet concentration of 64 (g/L). Some specific phosphate adsorption mechanisms for the pellets were revealed and the pellets showed the potential to efficiently adsorb phosphate from a huge amount of real wastewaters in an industrial scale.