Exploring the relationship between lactate metabolism and immunological function in colorectal cancer through genes identification and analysis

Introduction: Metabolic dysregulation is a widely acknowledged contributor for the development and tumorigenesis of colorectal cancer (CRC), highlighting the need for reliable prognostic biomarkers in this malignancy.Methods: Herein, we identified key genes relevant to CRC metabolism through a comprehensive analysis of lactate metabolism-related genes from GSEA MsigDB, employing univariate Cox regression analysis and random forest algorithms. Clinical prognostic analysis was performed following identification of three key genes, and consistent clustering enabled the classification of public datasets into three patterns with significant prognostic differences. The molecular pathways and tumor microenvironment (TME) of these patterns were then investigated through correlation analyses. Quantitative PCR was employed to quantify the mRNA expression levels of the three pivotal genes in CRC tissue. Single-cell RNA sequencing data and fluorescent multiplex immunohistochemistry were utilized to analyze relevant T cells and validate the correlation between key genes and CD4+ T cells.Results: Our analysis revealed that MPC1, COQ2, and ADAMTS13 significantly stratify the cohort into three patterns with distinct prognoses. Additionally, the immune infiltration and molecular pathways were significantly different for each pattern. Among the key genes, MPC1 and COQ2 were positively associated with good prognosis, whereas ADAMTS13 was negatively associated with good prognosis. Single-cell RNA sequencing (scRNA-seq) data illustrated that the relationship between three key genes and T cells, which was further confirmed by the results of fluorescent multiplex immunohistochemistry demonstrating a positive correlation between MPC1 and COQ2 with CD4+ T cells and a negative correlation between ADAMTS13 and CD4+ T cells.Discussion: These findings suggest that the three key lactate metabolism genes, MPC1, COQ2, and ADAMTS13, may serve as effective prognostic biomarkers and support the link between lactate metabolism and the immune microenvironment in CRC

Optimization of Flavonoid Extraction from <i>Abelmoschus manihot</i> Flowers Using Ultrasonic Techniques: Predictive Modeling through Response Surface Methodology and Deep Neural Network and Biological Activity Assessment

Understanding the optimal extraction methods for flavonoids from Abelmoschus manihot flowers (AMF) is crucial for unlocking their potential benefits. This study aimed to optimize the efficiency of flavonoid extraction from AMF. After comparing extraction methods, the ultrasonic cell crusher demonstrated superior performance over conventional techniques. Four key factors—solid-to-liquid ratio (1:10 to 1:50 g·mL−1), ethanol concentration (55% to 95%), ultrasonic time (10 to 50 min), and ultrasonic power (5% to 25% of 900 W)—were investigated and normalized using the entropy weight method. This led to a comprehensive evaluation (CE). Optimization of extraction conditions for the ultrasonic cell crusher was achieved through response surface methodology and a deep neural network model, resulting in optimal parameters: ethanol volume fraction of 66%, solid-to-liquid ratio of 1:21 g/mL, extraction efficiency of 9%, and extraction duration of 35 min, yielding a CE value of 23.14 (RSD Streptococcus mutans (S. mutans) were assessed. The results revealed that AMF extract (AMFE) exhibits inhibitory effects on S. mutans, with concomitant inhibition of sucrase and lactate dehydrogenase (LDH). The MIC of AMFE against planktonic S. mutans is 3 mg/mL, with an MBC of 6 mg/mL. Within the concentration range of 1/8 MIC to 2 MIC of AMFE, the activities of sucrase and LDH decreased by 318.934 U/mg prot and 61.844 U/mg prot, respectively. The antioxidant activity of AMFE was assessed using the potassium ferricyanide reduction and phosphomolybdenum methods. Additionally, the effect of AMFE on DPPH, ABTS, and ·OH free radical scavenging abilities was determined. The concentrations at which AMFE exhibited over 90% scavenging rate for ABTS and DPPH free radicals were found to be 0.125 mg/mL and 2 mg/mL, respectively

Protective effects of the Terminalia bellirica tannin-induced Nrf2/HO-1 signaling pathway in rats with high-altitude pulmonary hypertension

Abstract Background Oxidative stress and endothelial cell dysfunction induced by high-altitude hypoxia have important roles in the pathological process of high-altitude pulmonary hypertension (HAPH). Tannins present in Terminalia bellirica (Gaertn.) Roxb. (TTR) have pharmacological activities that produce oxidation resistance and exert anti-inflammatory effects. Whether TTR exerts a protective effect on HAPH remains unknown. Methods A rat model of HAPH was established. The mean pulmonary arterial pressure (mPAP) of the animals was measured, the serum levels of SOD, MDA, and GSH-Px were measured using ELISA, and the expression of Bax, Bcl-2, Nrf2, and HO-1 proteins in the lung tissue of each group of rats was measured using Western blotting. Pathological changes in the lung tissue were also observed. A model of damage to H2O2-induced pulmonary artery endothelial cells (PAECs) was generated, and cell proliferation was measured using CCK-8 assays. Flow cytometry was used to measure ROS levels in PAECs. Western blotting was used to detect the expression of Bax, Bcl-2, Nrf2, and HO-1 proteins in PAECs. Results The hemodynamic and pathologic findings showed that the mPAP of HAPH rats increased markedly, and the vascular wall thickness increased (P < 0.05). TTR reduced mPAP, alleviated or slowed pulmonary arterial remodeling, increased GSH-Px and SOD activity, lowered the level of MDA (P < 0.05), and downregulated the expression of Bax in the lung tissues of HAPH rats, while the expression of Bcl-2, Nrf2, and HO-1 was upregulated (P < 0.05). The results of the cell experiments showed that TTR inhibited H2O2-induced PAEC apoptosis and ROS production (P < 0.05), downregulated the expression of Bax in PAECs, and upregulated the expression of Bcl-2, Nrf2, and HO-1 (P < 0.05). Conclusion The results suggest that TTR reduces pulmonary arterial pressure, decreases oxidative stress during HAPH, and exerts protective effects in rats with HAPH and that its mechanism of action is related to regulation of the Nrf2/HO-1 signaling pathway

Improvement of Total Flavonoids from Dracocephalum moldavica L. in Rats with Chronic Mountain Sickness through 1H-NMR Metabonomics

Background. We analyzed the effects of total flavonoids from Dracocephalum moldavica L. (D. moldavica L.) on improving chronic mountain sickness (CMS) in rats using the NMR hydrogen spectrum (1H-NMR) metabonomics technology. Method. We extracted the total flavonoids of D. moldavica L with 60% ethanol reflux. A CMS model was established with 48 Sprague–Dawley (SD) rats, which were then randomly divided into six groups (n = 8): control group (normal saline, 0.4 mL/100 g/d, ig); model group (normal saline, 0.4 mL/100 g/d, ig); nifedipine group (nifedipine tablets, 2.7 mg/kg/d, ig); and high-, middle-, and low-dose groups of total flavonoids from D. moldavica L. (DML.H, DML.M, and DML.L, receiving total flavonoids from D. moldavica L. at 400, 200, and 100 mg/kg/d, ig, respectively). The sera of the rats in all the groups were determined, and NMR hydrogen spectrum metabolomics was analyzed. The serum contents of apolipoproteins A1 (Apo-A1) and E (Apo-E) were determined, and histopathological changes in the brain tissue of each group were observed. Results. Serum tests showed that total flavonoids from D. moldavica L. significantly increased the Apo-A1 and Apo-E levels in rats with CMS (P<0.05). The results of serum metabonomics showed that total flavonoids from D. moldavica L can alleviate amino acid, energy, and lipid metabolism disorders in rats with CMS. Pathohistological examination of brain tissue showed that these flavonoids improved pathological changes, such as meningeal vasodilation, hyperemia, edema of brain parenchyma, inflammatory cell infiltration, increase in perivascular space, and increase in pyramidal cells. Conclusion. Total flavonoids from D. moldavica L. have potential therapeutic effects on CMS. The possible mechanism is the reduction of oxidative damage through the alleviation of metabolism disorder

Immunomodulatory and antitumour effects of abnormal Savda Munziq on S180 tumour-bearing mice.

International audienceUNLABELLED: ABSTRACT: BACKGROUND: Abnormal Savda Munziq (ASMq), a traditional uyghur medicine, has shown anti-tumour properties in vitro. This study attempts to confirm these effects in vivo and measure effects on the immune system. METHODS: Kunming mice transplanted with Sarcoma 180 cells were treated with ASMq (2-8 g/kg/day) by intra-gastric administration compared to model and cyclophosphamide (20 mg/kg/day). After the 14th day post tumour implant, thymus, liver, spleen and tumours were removed, weighed, and processed for histopathological analysis. Blood samples were also taken for haematological and biochemical analyses including TNF-α , IL-1 β and IL-2. Splenic lymphocyte function was measured with MTT; lymphocyte subpopulations were measured by flow cytometry. RESULTS: ASMq treated animals had reduced tumour volume compared to model and increased concentrations of TNF-α, IL-1β and IL-2 compared to untreated and to cyclophosphamide-treated animals. No histopathological alterations were observed. The absence of viable S180 cells and the presence of necrotic cells and granulation tissue were observed in tumour tissue of treated animals. The effect on T lymphocytes was unclear. CONCLUSIONS: ASMq confirmed in vivo anti-tumour effects observed in vitro, which may be at least in part mediated by increased immune activity