Exploring the clinical efficacy and mechanism of high-position colon dialysis combined with Traditional Chinese Medicine retention enema in real-world patients with stage 3-5 chronic kidney disease (non-dialysis) based on the theory of the Gut-Kidney axis.

Background: With societal and economic development, the annual incidence of chronic kidney disease (CKD) is increasing. Current treatments for CKD are limited, and once patients progress to the uraemic stage, it places a significant economic burden on families and society. Based on the "gut-kidney axis" theory and real-world research, this study aims to evaluate the clinical efficacy, safety, and potential mechanism of high-position colon dialysis combined with traditional Chinese medicine (TCM) retention enema in treating stage 3-5 chronic kidney disease (non-dialysis). Additionally, it seeks to identify new therapeutic targets and approaches for CKD treatment. Methods: The TCM decoction was analyzed using Ultra-Performance Liquid Chromatography-Quadrupole-Orbitrap-High Resolution Mass Spectrometry (UPLC-Q-Orbitrap-HRMS). Participants meeting the inclusion criteria were divided into a control group (n = 153) and a treatment group (n = 159) based on their preferences and physicians' recommendations. Both groups adhered to a high-quality low-protein, low-salt, low-phosphorus, and low-fat diet supplemented with essential amino acids, and were monitored for blood pressure, blood glucose, and blood lipids. The treatment group received high-position colon dialysis combined with TCM retention enemas (administered at least 12 times every other day). Results: Thirteen compounds were identified from the herbs by UPLC-Q-Orbitrap-HRMS. The CKD3-5 treatment group exhibited improvements in blood biochemistry and other laboratory indices, with significant enhancements in renal function-related indices for CKD4 and CKD5 stages (p < 0.05). Following treatment, indoxyl sulfate (IS), endotoxin, and D-lactic acid levels decreased to a certain extent in both groups, with a statistically significant difference observed within the treatment group (p < 0.05). The treatment group displayed a significant reduction in aerobic bacterial colonies, an increase in anaerobic bacterial colonies, a decrease in Escherichia coli colonies, and an increase in Bifidobacterium and Lactobacillus colonies (p < 0.05). No significant changes in colony numbers were observed in the control group. Conclusion: High-position colon dialysis combined with TCM retention enema may serve as an adjuvant treatment for CKD4-5 (non-dialysis), and its mechanism may be related to the reduction of uraemic toxins, improvement of intestinal mucosal barrier function, and regulation of intestinal microecology. Clinical Trial Registration: https://www.chictr.org.cn/, identifier ChiCTR2200062852.

Osmundacetone modulates mitochondrial metabolism in non-small cell lung cancer cells by hijacking the glutamine/glutamate/α-KG metabolic axis.

BACKGROUND: Osmundacetone (OSC) is a bioactive phenolic compound isolated from Phellinus igniarius and that was shown to exert cytotoxic effects on cancer cells in our previous work. The antiproliferative impact of OSC on non-small cell lung cancer (NSCLC) and the underlying mechanisms, however, have not been studied. PURPOSE: This study aimed to explore the antiproliferative effect of OSC on NSCLC cells and the mechanisms involved. METHODS: Cell viability, colony formation and cell cycle distribution were measured following exposure to OSC in vitro. The anticancer activity of OSC was also examined using a xenograft growth assay in vivo. Furthermore, serum metabolomics analysis by GC-MS was done to detect alterations in the metabolic profile. Next, expression of GLS1 and GLUD1, the key enzymes in glutamine metabolism, was evaluated using RT-PCR and western blot. α-KG and NADH metabolites were assessed by ELISA. Mitochondrial functions and morphology were evaluated using the JC-1 probe and transmission electron microscopy, respectively. The ATP production rate in mitochondria of cells with OSC treatment was determined using a Seahorse XFe24 Analyzer. RESULTS: OSC selectively reduced the proliferation of A549 and H460 cells. OSC triggered G2/M cell cycle arrest and decreased the cell clone formation. A mouse xenograft model revealed that OSC inhibited tumor growth in vivo. Findings of serum metabolomics analyses indicated that the anticancer function of OSC was related to disorders of glutamine metabolism. Such a speculation was further verified by the expression level of GLUD1, which was downregulated by OSC treatment. Concentrations of the related metabolites α-KG and NADH were reduced in response to OSC treatment. Moreover, OSC led to disorganization of the mitochondrial ultrastructure and a decrease in mitochondrial membrane potential. OSC also decreased ATP production via oxidative phosphorylation (OXPHOS) but did not affect glycolysis in NSCLC cells. CONCLUSION: The key role of OSC in mitochondrial energy metabolism in NSCLC cells is to suppress tumor development and cell proliferation downregulating GLUD1 to inhibit the glutamine/glutamate/α-KG metabolic axis and OXPHOS. It indicats that OSC might be a potential natural agent for personalized medicine and an anticancer metabolic modulator in NSCLC chemotherapy.

The anticancer effect of extract of medicinal mushroom Sanghuangprous vaninii against human cervical cancer cell via endoplasmic reticulum stress-mitochondrial apoptotic pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Sanghuangprous vaninii (Ljub.) L.W. Zhou & Y.C. Dai, known as "Sanghuang" in China, is mainly distributed in the northeast of China. As a traditional medicinal mushroom, "Sanghuang" is medicinally used for resolving the symptoms of gynecological tumors including vaginal bleeding, leucorrhea, abdominal pain and abdominal mass. This mushroom is potential for gynecological cancers therapy. However, there is a lack of scientific evidence on its anti-tumor activity against human cervical cancer, the most common gynecological cancer. AIM OF THE STUDY: To identify the anti-tumor potential of the extract of Sanghuangprous vaninii (ESV) on human cervical cancer SiHa cells, and explore detailed mechanisms of ESV inducing cancer cell death. MATERIALS AND METHODS: The anti-proliferation effects were evaluated by Cell Counting Kit-8 (CCK8) assay. Transmission electron microscope was applied to determined the cellular ultrastructure changes. The cell cycle distribution, quantification of apoptotic cells, mitochondrial transmembrane potential, reactive oxygen species (ROS) level, and cytosolic calcium level were determined by flow cytometer. Western blot analysis was used to explore the alterations in the expression levels of endoplasmic reticulum stress-marked and apoptosis-related proteins. The in-vivo anti-tumor effect was identified by mouse xenograft model. RESULTS: ESV significantly inhibited the proliferation of SiHa cells in vivo and vitro. Blocking cell cycle and causing cell apoptosis contributed to cell death induced by ESV. Mechanistically, ESV induced endoplasmic reticulum stress evidenced by the elevated expressions of GRP78 and CHOP, which accompanied by the release of calcium (Ca2+). The Ca2+ overload and oxidative stress facilitated the collapse of mitochondrial membrane potential and subsequently activated caspase-3 and -9, which eventually lead to cell apoptosis. CONCLUSIONS: Our results revealed that Sanghuangprous vaninii was effective against human cervical cancer SiHa cells in vitro and vivo. There is a promising potential that Sanghuangprous vaninii might be a candidate for cervical cancer therapy.

Effect of Chinese medicine prescription on nephrotic syndrome: A protocol for systematic review and meta-analysis.

BACKGROUND: Nephrotic syndrome (NS) is a common chronic recurrent kidney disease. Many trials have shown that Chinese medicine prescription (CMP) can effectively treat NS. The program aims to evaluate the efficacy and safety of CMP for NS. METHODS: This systematic evaluation will entail an electronic and manual search of all CMP for NS from inception to February, 2020, regardless of the publication status or language. Databases include PubMed, Embase, Springer, Web of Science, the Cochrane Library, the World Health Organization International Clinical Trial Registration Platform, the Chinese Medicine Database, the China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the China Science Journal Database, and the Wanfang Database. Other sources of information, including bibliographies and meeting minutes for identified publications, will also be searched. A manual search for grey literature, including unpublished conference articles will be performed. Additionally, any clinical randomized controlled trials related to CMP for NS, regardless of the publication status and language limitations, will be included in the study. Study selection, data extraction, and research quality assessments will be conducted independently by 2 researchers. The main result was the total clinical efficacy rate or other validated scales after at least 2 weeks of treatment. Secondary outcomes included 24-hour urine protein quantification, blood urea nitrogen, serum creatinine, C-reactive protein, tumor necrosis factor-α, and interleukin 6, recurrence rates and adverse events during follow-up. Implement the Cochrane RevMan V5.3 bias assessment tool to assess bias risk, data integration risk, meta-analysis risk, and subgroup analysis risk (if conditions are met). Mean difference, standard mean deviation and binary data will be used to represent continuous results. RESULTS: This study will provide a comprehensive review and evaluation of CMP for the treatment of NS. CONCLUSION: This study will provide new evidence for evaluating the effectiveness and side effects of CMP on NS. Since the data is not personalized, formal ethical approval is not required. INPLASY REGISTRATION NUMBER: INPLASY202040181.

Health risk assessment of heavy metals in agricultural soils and identification of main influencing factors in a typical industrial park in northwest China.

The accumulation of heavy metals (HMs) in the soil poses a threat to human health. In this study, 62 pairs of topsoil and wheat grain samples were collected from a typical industrial park in northwest China, and the human health risks associated with cadmium (Cd), chromium (Cr), copper (Cu), mercury (Hg), nickel (Ni), lead (Pb) and zinc (Zn) were assessed through multiple exposure pathways. Meanwhile, the contribution of different environmental factors and their interactions were explored by using geo-detector. Results showed that Cd concentration in the soil ranged from 0.307 to 2.491 mg kg-1, with a median value of 0.588 mg kg-1, and almost half of the samples exceeded the pollution threshold. In comparison, other elements in the soil were below their mandatory thresholds. However, it is noteworthy that in addition to the median Cd concentration in wheat grains of 0.062 mg kg-1 (0.018-0.246 mg kg-1), the Pb concentration also reached 0.2 mg kg-1 (0.1-0.7 mg kg-1), with a sample over-standard rate of 48.39%. In addition, the health risk assessment results showed that the average total hazard index (HIt) for adults and children was 1.22 and 1.53, and the total carcinogenic risk (TCRt) was 7.0 × 10-4 and 2.32 × 10-4, respectively, both above acceptable criteria. Dietary intake was the main route of exposure. Among various factors, distance from industrial enterprises, altitude, and soil pH, distance from major roads were the most influential contributors. Their interactions were more prominent than the effects of single factors and this synergy deserves attention.