[Total polyphenols of Cydonia oblonga inhibited proliferation and migration of renal cancer cells by PI3K/Akt/mTOR pathway].

The mechanism of total polyphenols of Cydonia oblonga Miller(TPCOM) against kidney cancer was elucidated through a combination of network pharmacology, bioinformatics, and experimental verification. The active polyphenolic compounds from C. oblonga were screened by network pharmacological techniques and kidney cancer-related targets were collected through the database. The differential gene expression analysis was performed on RNA sequencing data from tumor tissue and normal tissue of kidney cancer patients obtained from the Gene Expression Omnibus(GEO) database. The results of network pharmacology predictions and differential gene expression analysis were used to identify the core genes targeted by TPCOM in kidney cancer. Survival analysis was conducted to identify key targets that could impact patient survival, followed by Kyoto Encyclopedia of Genes and Genomes(KEGG) and Gene Ontology(GO) enrichment analyses. Cell proliferation and activity experiments(cell counting kit-8) were conducted using TPCOM at concentrations ranging from 20 to 640 µg·mL~(-1) on 786-O and Renca cells. Additionally, TPCOM at concentrations of 40, 80, and 160 µg·mL~(-1) was applied to kidney cancer cells to assess its effect on cell migration and its regulation of protein expression levels related to the protein kinase B(Akt), mammalian target of rapamycin(mTOR), and phosphoinositide 3-kinase(PI3K) signaling pathways. Network pharmacology predicted eight active polyphenolic compounds from C. oblonga. Survival analysis revealed 15 significantly differentially expressed genes in kidney cancer that were affected by TPCOM and had a significant impact on patient survival. KEGG and GO analysis results indicated that these 15 targets were primarily associated with the PI3K/Akt signaling pathway, cell migration, and proliferation. The results showed that TPCOM could inhibit the proliferation of 786-O and Renca cells, with IC_(50) values of 121.4 and 137.9 µg·mL~(-1), respectively. TPCOM was also found to inhibit the migration of these cells and suppress the PI3K/Akt/mTOR signaling pathway. TPCOM may exert its anti-kidney cancer effects by inhibiting the activation of the PI3K/Akt/mTOR signaling pathway, thereby restraining the proliferation and migration of kidney cancer cells. This study provides a foundation for the research on the anti-tumor effects of natural product C. oblonga, particularly in Xinjiang, and holds significance for further promoting its development and utilization.

Mechanistic research: Selenium regulates virulence factors, reducing adhesion ability and inflammatory damage of Helicobacter pylori.

BACKGROUND: The pathogenicity of Helicobacter pylori is dependent on factors including the environment and the host. Although selenium is closely related to pathogenicity as an environmental factor, the specific correlation between them remains unclear. AIM: To investigate how selenium acts on virulence factors and reduces their toxicity. METHODS: H. pylori strains were induced by sodium selenite. The expression of cytotoxin-associated protein A (CagA) and vacuolating cytotoxin gene A (VacA) was determined by quantitative PCR and Western blotting. Transcriptomics was used to analyze CagA, CagM, CagE, Cag1, Cag3, and CagT. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction, and H. pylori colonization, inflammatory reactions, and the cell adhesion ability of H. pylori were assessed. RESULTS: CagA and VacA expression was upregulated at first and then downregulated in the H. pylori strains after sodium selenite treatment. Their expression was significantly and steadily downregulated after the 5th cycle (10 d). Transcriptome analysis revealed that sodium selenite altered the levels affect H. pylori virulence factors such as CagA, CagM, CagE, Cag1, Cag3, and CagT. Of these factors, CagM and CagE expression was continuously downregulated and further downregulated after 2 h of induction with sodium selenite. Moreover, CagT expression was upregulated before the 3rd cycle (6 d) and significantly downregulated after the 5th cycle. Cag1 and Cag3 expression was upregulated and downregulated, respectively, but no significant change was observed by the 5th cycle. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction. The extent of H. pylori colonization in the stomach increased; however, sodium selenite also induced a mild inflammatory reaction in the gastric mucosa of H. pylori-infected mice, and the cell adhesion ability of H. pylori was significantly weakened. CONCLUSION: These results demonstrate that H. pylori displayed virulence attenuation after the 10th d of sodium selenite treatment. Sodium selenite is a low toxicity compound with strong stability that can reduce the cell adhesion ability of H. pylori, thus mitigating the inflammatory damage to the gastric mucosa.

Effect of Cydonia oblonga Mill. leaf extracts or captopril on blood pressure and related biomarkers in renal hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cydonia oblonga Mill. (COM) is used in traditional Uyghur medicine to treat or prevent cardiovascular disease. In a previous study COM leaf extracts were found to be active in renal hypertensive rats (RHR). The present study tests the dose-dependence of the effect of ethanol leaf extracts on hypertension and on biomarkers associated with blood pressure control, such as angiotensin-II (AII), plasma renin activity (PRA), apelin-12 (A), endothelin (ET) and nitric oxide (NO), compared to captopril. METHODS: Two-kidney one-clip (2K1C) Goldblatt model rats were divided randomly into six groups: sham, model, captopril 25 mg/kg, COM leaf extract 80, 160 and 320 mg/kg (n=10 each). Drugs were administered orally daily for eight weeks. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured before treatment and every 2 weeks. Blood and kidney samples were collected after the last treatment to measure AII, PRA, A, ET and NO. RESULTS: RHR had increased blood pressure, AII, A, PRA, ET and decreased NO. Treatment with captopril reduced blood pressure, AII, A, PRA, and ET, though not quite to normal values. COM leaf extracts significantly and dose-dependently reduced blood pressure, AII, A, RA and ET, whereas NO was increased. The highest dose of COM had the same effects as captopril. CONCLUSION: The effects of COM extracts on blood pressure and biomarkers were dose-dependent and at the highest dose similar to those of captopril. This suggests an action of COM on the renin-angiotensin system, which could explain its antihypertensive effect.

Pathological Changes in Internal Organs after Blocking Low Hydraulic Resistance Channels along the Stomach Meridian in Pigs.

Objective. The correlation between meridians and organs (Zang-fu) is an important aspect of meridian theory. The objective of this paper is to investigate the pathological changes in the organs resulting from blocking low hydraulic resistance channel (LHRC) along the stomach meridian by injecting gel in pigs so as to offer some insight into the correlation between meridians and internal organs. Methods. Four white piglets and twelve black minipigs were divided into four batches and were observed in different periods. Each batch included two pairs of pigs and each pair matched two pigs with similar conditions among which gel was injected into 6~8 low hydraulic resistance points along the the stomach meridian in the experimental pig and the same amount of saline was injected into the same points in the control pig. The state of stomach and intestine was observed 6~10 weeks after the blocking model was developed. Results. The results showed that there were bloated stomach or/and intestine in all the experimental pigs while there were normal states in seven control pigs except one dead during the experiment. Conclusion. The findings confirmed that the blockage of LHRC along the stomach meridian can influence the state of stomach and intestine, leading to a distension on stomach or/and intestine.

Study on the Formation of Novel Threadlike Structure through Intravenous Injection of Heparin in Rats and Refined Observation in Minipigs.

Objective. To study if the novel threadlike structure (NTS) was caused by coagulation during injecting urethane intraperitoneally and the source of NTS. Methods. Twenty-two SD rats were anaesthetized by urethane injected intraperitoneally. Heparin was injected at 5 minutes before the anaesthesia from femoral vein in 11 rats, and saline was given in the other 11 rats randomly. Six Chinese minipigs were carried to look for NTS. One sample was taken to be stained by DAPI/Phalloidin and observed by a laser scanning confocal microscope. Results. In the group of heparin, 10 rats were found to have NTS with appearance rate of 90.9%, and 9 rats were found to have NTS with the appearance rate of 80.1%. Both groups have 1.81 average numbers of NTS in each rat without significant difference (P > 0.05). In the observation of pigs, the NTS was found to prolong from the serous membranes of abdominal wall and organ surface. Histological observation showed elongated nuclei and alignment which is similar to the characteristics of PVS. Conclusion. There is no strong evidence to say that the NTS on organ surface was caused by coagulation of blood. The source of NTS might be a prolonged structure from serous membrane in abdominal cavity during the development and more or less retained after birth.