Non-cytotoxic nanomolar concentration of arctigenin protects neuronal cells from chemotherapy-induced ferroptosis by regulating SLC7A11-cystine-cysteine axis.

Neurotoxicity is a common side effect of certain types of therapeutic drugs, posing a major hurdle for their clinical application. Accumulating evidence suggests that ferroptosis is involved in the neurotoxicity induced by these drugs. Therefore, targeting ferroptosis is considered to be a reasonable approach to prevent such side effect. Arctigenin (ATG) is a major bioactive ingredient of Arctium lappa L., a popular medicinal plant in Asia, and has been reported to have multiple bioactivities including neuroprotection. However, the mechanisms underlying the neuroprotection of ATG has not been well elucidated. The purpose of this study was to investigate whether the neuroprotection of ATG was associated with its ability to protect neuronal cells from ferroptosis. Using neuronal cell ferroptosis model induced by either classic ferroptosis induces or therapeutic drugs, we demonstrated for the first time that ATG in the nanomolar concentration range effectively prevented neuronal cell ferroptosis induced by classic ferroptosis inducer sulfasalazine (SAS) and erastin (Era), or therapeutic drug oxaliplatin (OXA) and 5-fluorouracil (5-FU). Mechanistically, we uncovered that the anti-ferroptotic effect of ATG was attributed to its ability to activate SLC7A11-cystine-cysteine axis. The findings of the present study implicate that ATG holds great potential to be developed as a novel agent for preventing SLC7A11 inhibition-mediated neurotoxicity.

Clinical practice guidelines for prevention and treatment of postoperative gastrointestinal disorder with Integrated Traditional Chinese and Western Medicine (2023).

Postoperative gastrointestinal disorder (POGD) was a common complication after surgery under anesthesia. Strategies in combination with Traditional Chinese Medicine and Western medicine showed some distinct effects but standardized clinical practice guidelines were not available. Thus, a multidisciplinary expert team from various professional bodies including the Perioperative and Anesthesia Professional Committees of the Chinese Association of Integrative Medicine (CAIM), jointly with Gansu Province Clinical Research Center of Integrative Anesthesiology/Anesthesia and Pain Medical Center of Gansu Provincial Hospital of Traditional Chinese Medicine and WHO Collaborating Center for Guideline Implementation and Knowledge Translation/Chinese Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Center/Gansu Provincial Center for Medical Guideline Industry Technology/Evidence-based Medicine Center of Lanzhou University, was established to develop evidence-based guidelines. Clinical questions (7 background and 12 clinical questions) were identified through literature reviews and expert consensus meetings. Based on systematic reviews/meta-analyses, evidence quality was analyzed and the advantages and disadvantages of interventional measures were weighed with input from patients' preferences. Finally, 20 recommendations were developed through the Delphi-based consensus meetings. These recommendations included disease definitions, etiologies, pathogenesis, syndrome differentiation, diagnosis, and perioperative prevention and treatment.

18ß-glycyrrhetinic acid suppresses Lewis lung cancer growth through protecting immune cells from ferroptosis.

PURPOSE: 18ß-glycyrrhetinic acid (GA), the main metabolite of glycyrrhizic acid extracted from the root of licorice, has been reported to possess anti-cancer and immunomodulatory activity, but the mechanisms are not well understood. Recent studies have shown that ferroptosis of immune cells is involved in tumor-associated immune suppression. The purpose of this study was to investigate whether the enhanced immune response via inhibiting immune cell ferroptosis contributed to the anticancer effect of 18ß-GA. METHODS: Lewis Lung carcinoma mouse model and Murine CD8 + T cell culture model were used to examine the changes of immune response and ferroptosis of immune cells. RESULTS: We found that 18ß-GA was effective against lung cancer accompanied by enhanced activation of tumor-infiltrating CD8+ T cells in Lewis Lung carcinoma mouse model. Furthermore, we demonstrated that the boosted immune response by GA was attributed to its ability to inhibit arachidonic acid (AA)-mediated CD8+ T ferroptosis via suppressing CD36 expression. CONCLUSION: The findings of the present study unraveled a novel mechanism underlying the anti-cancer and immunomodulatory activity of 18ß-GA and support that 18ß-GA holds potential to be used as an immune enhancer for lung cancer prevention or treatment.

Therapeutic role of Wuda granule in gastrointestinal motility disorder through promoting gastrointestinal motility and decreasing inflammatory level.

Introduction: Previous studies indicated that Wuda Granule (WDG) has been applied in the treatment of gastrointestinal motility disorder (GMD), but the effect and underlying mechanisms is yet to be elucidated. This study aimed to explore the mechanism and pharmacological effect of WDG for GMD via network analysis, verification of animal experiments and clinical experiments. Methods: The chemical components of WDG were identified from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP, http://lsp.nwu.edu.cn/index.php), and the Encyclopedia of Traditional Chinese Medicine (ETCM, http://www.tcmip.cn/ETCM/index.php/Home/Index/) according to oral bioavailability (OB) ≥ 20% and drug-likeness (DL) ≥ 0.10. The targets of WDG compounds were retrieved from the Swiss Target Prediction database (http://www.swisstargetprediction.ch/) and targets related to GMD were retrieved from GeneCards database (https://www.genecards.org/). Network analysis were performed to screen the key active compounds of WDG and its hub targets. Then the pharmacological effect of WDG were verified via vivo experiments in rats and clinical experiments. Results: The results showed that 117 effective active compounds of WDG were screened and 494 targets of WDG compounds targeting GMD were selected. These targets were involved in the biological process of inflammatory regulation and the regulation of gastrointestinal motility. The mechanism was mainly involved in the regulation of PI3K-Akt signaling pathway and Rap1 signaling pathway. In addition, molecular docking analysis suggested that eight key active compounds of WDG may be mainly responsible for the effect of WDG on GMD by targeting HARS, AKT, and PIK3CA, respectively. Animal experiments and clinical trials both suggested that WDG could exert therapeutical effect on GMD via inhibiting inflammation and promoting gastrointestinal motility, it could also improve digestive function of patients with laparoscopic colorectal cancer after surgery. Conclusion: This study was the first to demonstrate that WDG improved GMD mainly via inhibiting inflammatory level and promoting gastrointestinal motility, providing new insights for the understanding of WDG for GMD, inspiration for future research and reference for clinical strategy in terms of the treatment of GMD.

Managing ferroptosis-related diseases with indirect dietary modulators of ferroptosis.

Ferroptosis is an iron-dependent form of programmed cell death driven by excessive oxidation of polyunsaturated phospholipids on cellular membranes. Accumulating evidence suggests that ferroptosis has been implicated in the pathological process of various diseases, such as cardiovascular diseases, neurological diseases, liver diseases, kidney injury, lung injury, diabetes, and cancer. Targeting ferroptosis is therefore considered to be a reasonable strategy to fight against ferroptosis-associated diseases. Many dietary bioactive agents have been identified to be able to either suppress or promote ferroptosis, indicating that ferroptosis-based intervention by dietary approach may be an effective strategy for preventing and treating diseases associated with ferroptosis dysregulation. In this review, we summarize the present understanding of the functional role of ferroptosis in the pathogenesis of aforementioned diseases with an emphasis on the evidence of managing ferroptosis-related diseases with indirect dietary modulators of ferroptosis and propose issues that need to be addressed to promote practical application of dietary approach targeting ferroptosis.

Xanthohumol inhibits non-small cell lung cancer via directly targeting T-lymphokine-activated killer cell-originated protein kinase.

Xanthohumol is a principal prenylated chalcone isolated from hops. Previous studies have shown that xanthohumol was effective against various types of cancer, but the mechanisms, especially the direct targets for xanthohumol to exert an anticancer effect, remain elusive. Overexpression of T-lymphokine-activated killer cell-originated protein kinase (TOPK) promotes tumorigenesis, invasion and metastasis, implying the likely potential for targeting TOPK in cancer prevention and treatment. In the present study, we found that xanthohumol significantly inhibited the cell proliferation, migration and invasion of non-small cell lung cancer (NSCLC) in vitro and suppressed tumor growth in vivo, which is well correlated with inactivating TOPK, evidenced by reduced phosphorylation of TOPK and its downstream signaling histone H3 and Akt, and decreased its kinase activity. Moreover, molecular docking and biomolecular interaction analysis showed that xanthohumol was able to directly bind to the TOPK protein, suggesting that TOPK inactivation by xanthohumol is attributed to its ability to directly interact with TOPK. The findings of the present study identified TOPK as a direct target for xanthohumol to exert its anticancer activity, revealing novel insight into the mechanisms underlying the anticancer activity of xanthohumol.

Identification of key modules and candidate genes associated with endometriosis based on transcriptome data via bioinformatics analysis.

BACKGROUNDS: Endometriosis is a common disease in women, but the signaling pathways and genes involved remain unclear. This study screened genes that were differentially expressed in ectopic endometrium (EC) and eutopic endometrium (EU) in endometriosis and provided clues for subsequent experimental verification. METHODS: Endometriosis samples were harvested from inpatients that underwent surgery from 2017 to 2019 with pathological evidence of endometriosis. We assessed the mRNA expression profiles in endometriosis and further conducted gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene Set Enrichment Analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) to identify potential biomarkers in endometriosis. Finally, we further validated hub genes using public databases and immunohistochemistry assays. RESULTS: The upregulated DEGs of ectopic endometrium from endometriosis patients were mainly involved in cell adhesion, MAPK signaling, PI3K-Akt signaling pathways, cytokine receptor interactions, and epithelial-mesenchymal transformation (EMT)-associated signaling pathways. The downregulated DEGs between ectopic endometrium and eutopic endometrium were related to decidualization-associated genes in endometriosis. The correlated gene modules in eutopic endometrial cells were mainly enriched in cell adhesion, embryo implantation and inflammation. The eutopic and ectopic endometrial lesions in endometriosis were involved in the EMT process. Furthermore, we identified 18 co-expression modules during WGCNA analysis. Hub genes in the pale turquoise module were FOSB, JUNB, ATF3, CXCL2, FOS, etc. Significantly enriched KEGG pathways included the TNF, MAPK, foxO, oxytocin, and p53 signaling pathways. Enrichment pathways were directly related to immune surveillance, stem cell self-renewal, and epithelial-mesenchymal transformation. Several pathways and modules of endometriosis are related to cancer-associated pathways, which substantiates the correlation between endometriosis and various gynecological tumors. CONCLUSIONS: Endometriosis was tightly correlated with EMT and fibrosis mediated by inflammatory immunity, cytokines, estrogen, kinases and protooncogene through transcriptomics. Overall, our findings lay the groundwork for understanding the pathogenesis of endometriosis and its relationship with malignant transformation.

Risk of fracture following gastric surgery for benign and malignant conditions: A study level pooled analysis of population-based cohort studies.

Background: Metabolic changes may occur following gastric surgery, which has been reported to contribute to bone loss, osteoporosis and even bone fracture. However, the evidence regarding the relationship between gastric surgery for benign and malignant conditions and risk of fracture is controversial. This study was conducted with the aim to evaluate whether gastric surgery is associated with a high risk of fracture. Methods: Major electronic databases were searched from inception through October 2021 for population-based cohort studies investigating the associations between gastric surgery (including bariatric gastric surgeries and surgeries for gastric benign and malignant gastric tumors) and risk of fracture compared with controls. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were derived using the random-effects Mantel-Haenszel model. Multiple subgroup analyses and sensitivity analyses were carried out to test sources of heterogeneity stratified by various study characteristics and the robustness of the results. Results: A total of 14 studies comprising 693134 individuals were identified for analysis. The RR for the risk of fracture in people undergoing gastric surgery was 1.45 [95% confidence interval (CI) 1.23 - 1.72; I2 = 95.8%; P < 0.001] compared with that in control populations, among which the fracture sites of upper limb, spine, lower limb, pelvis and hip showed consistent significant results (all P < 0.05), whereas nonsignificant associations was noted for other fracture sites. Significant associations were also observed for patients having total or subtotal gastrectomy (RR 2.22, 95% CI 1.66 to 3.00), gastric bypass (RR 1.48, 95% CI 1.26 to 1.74), and a similar trend was observed for preserved passage procedures (including sleeve gastrectomy, gastric banding, vertical banded gastroplasty and other procedures that preserved the passage through the duodenum and proximal small bowel, in contrast to gastric bypass), though the difference did not reach statistically significant (RR 1.10, 95% CI 0.95 to 1.26). An evident increased risk in the age range from 40-59 years was observed (40-49 years: RR 1.36, 95% CI 1.19-1.55; 50-59 years: RR 2.48, 95% CI 1.58-3.90). Conclusion: From this large pooled analysis of population-based cohort studies, evidence supports that fracture risk is increased in gastric surgery survivors compared with the control population. Early prevention and effective intervention strategies of bone fracture should be taken from clinicians and health policy makers. Clinical Trial Registration: PROSPERO (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=291394), identifier CRD42021291394.

18ß-glycyrrhetinic acid protects neuronal cells from ferroptosis through inhibiting labile iron accumulation and preventing coenzyme Q10 reduction.

Ferroptosis is a new form of iron-dependent cell death. A growing body of evidence suggests that abnormal ferroptosis is involved in developing neurodegenerative diseases. 18ß-glycyrrhetinic acid (GA) is a major bioactive component of licorice with multiple biological activities including neuroprotection. Give the role of ferroptosis in the neurodegenerative diseases, we hypothesized that the neuroprotective effect of GA might be associated with its ability to protect neuro-cells from ferroptosis. Results demonstrated that GA was able to prevent a well-known ferroptosis inducer ferroptosis inducer 56 (FIN56)-triggered ferroptosis in HT22 mouse neuronal cell. Further mechanistic investigation revealed that the protection of GA on ferroptosis is attributed its inhibiting effect on cellular labile iron accumulation and up-regulating coenzyme Q10 (CoQ10) levels. The findings of the present study uncovered a novel mechanism involved in the neuroprotective effect of GA, and imply that GA could be developed as a novel agent to manage ferroptosis-related diseases.

Patulin disrupts SLC7A11-cystine-cysteine-GSH antioxidant system and promotes renal cell ferroptosis both in vitro and in vivo.

Patulin (PAT) is a common food-borne mycotoxin with diverse toxic effects including nephrotoxicity. The induction of oxidative stress is suggested to be a key mechanism contributed to toxicities of PAT. Reduced glutathione (GSH), a sulfhydryl-containing tripeptide, is a key reason for PAT-mediated oxidative stress. Cystine/glutamate antiporter (system xc-)-mediated cystine uptake plays a critical role in maintaining redox balance via promoting GSH biosynthesis. In this study, we addressed if GSH reduction by PAT was associated with inhibition of system xc--mediated GSH biosynthesis. Results showed that PAT significantly decreased activity of SLC7A11, a core subunit of system xc-, through activating AMPK-mediated formation of beclin1-SLC7A11 complex. Furthermore, PAT promoted ferroptosis induced by a known ferroptosis inducer RSL3 in normal renal cells, and exacerbated folic acid-induced nephrotoxicity in a mouse model of acute kidney injury. The findings of the present study provide new insights into PAT-induced kidney toxicity, and implicate that patients with ferroptosis-associated diseases maybe more susceptible to PAT.

Effect of Wuda granule on gastrointestinal function recovery after laparoscopic intestinal resection: a randomized-controlled trial.

BACKGROUND: Previous studies have suggested that the Wuda granule (WDG) could promote the recovery of gastrointestinal (GI) function after gynecologic abdominal surgery. This trial aimed to investigate the efficacy and safety of WDG in the rapid recovery of GI function in patients after laparoscopic intestinal resection in the setting of enhanced recovery after surgery (ERAS)-based perioperative care. METHODS: We performed a randomized, double-blind, placebo-controlled pilot trial. Thirty patients who met the inclusion criteria were randomly assigned to either the WDG group or the placebo group in a 1:1 ratio. The patients received WDG or placebo twice a day in addition to ERAS-based perioperative care, starting on post-operative Day 1 until Day 3. The primary outcomes were time to first bowel movement and time to first tolerance of solid food. The secondary outcomes were time to first flatus, length of hospital stay (LOS), and post-operative ileus-related morbidity. Adverse events were also recorded. RESULTS: There were no statistically significant differences in baseline characteristics between the two groups. The median time to first bowel movement was significantly decreased in the WDG group compared with the control group (27.6 vs 50.1 h; P < 0.001), but the median times to first flatus (22.9 vs 25.1 h; P > 0.05) and LOS (5.0 vs 5.0 days; P > 0.05) were not statistically different. The occurrence rates of post-operative nausea, vomiting, abdominal distension, and abdominal pain were similar in the two groups. No adverse events occurred in any patients. CONCLUSIONS: The addition of WDG to ERAS post-operative care after laparoscopic intestinal resection can safely promote the rapid recovery of GI function.

Glucose Limitation Sensitizes Cancer Cells to Selenite-Induced Cytotoxicity via SLC7A11-Mediated Redox Collapse.

Combination of intermittent fasting and chemotherapy has been drawn an increasing attention because of the encouraging efficacy. In this study, we evaluated the anti-cancer effect of combination of glucose limitation and selenite (Se), a representative inorganic form of selenium, that is preferentially accumulated in tumors. Results showed that cytotoxic effect of selenite on cancer cells, but not on normal cells, was significantly enhanced in response to the combination of selenite and glucose limitation. Furthermore, in vivo therapeutic efficacy of combining selenite with fasting was dramatically improved in xenograft models of lung and colon cancer. Mechanistically, we found that SLC7A11 expression in cancer cells was up-regulated by selenite both in vitro and in vivo. The elevated SLC7A11 led to cystine accumulation, NADPH depletion and the conversion of cystine to cysteine inhibition, which in turn boosted selenite-mediated reactive oxygen species (ROS), followed by enhancement of selenite-mediated cytotoxic effect. The findings of the present study provide an effective and practical approach for increasing the therapeutic window of selenite and imply that combination of selenite and fasting holds promising potential to be developed a clinically useful regimen for treating certain types of cancer.

A Multi-Ingredient Formula Ameliorates Exercise-Induced Fatigue by Changing Metabolic Pathways and Increasing Antioxidant Capacity in Mice.

Multiple mechanisms are involved in exercise-induced fatigue, including energy depletion, metabolite accumulation, and oxidative stress, etc. The mechanistic findings provide a rationale for a multi-targeted approach to exercise-induced fatigue management. This study created a multi-ingredient formula mixed with valine, isoleucine, leucine, ß-alanine, creatine, l-carnitine, quercetin, and betaine, based on the functional characteristics of these agents, and evaluated the preventive effect of this mechanism-based formula on exercise-induced fatigue. Results showed that the 7-d formula supplement significantly increased the running duration time of mice by 14% and the distance by 20% in an exhaustive treadmill test, indicating that the formula could delay fatigue appearance and improve exercise performance. Mechanistically, the formula enhanced fatty acid oxidation and spared liver glycogen by regulating the fat/glucose metabolism-related signaling pathways, including phospho-adenosine monophosphate-activated protein kinase α (p-AMPKα), phospho-acetyl CoA carboxylase (p-ACC), carnitine palmitoyl-transferase 1B (CPT1B), fatty acid translocase (CD36), and glucose transporter type 4 (GLUT4), and increased antioxidant capacity. The findings suggested that the formula tested in this study effectively ameliorated exercise-induced fatigue by targeting multi-signaling pathways, showing promise as a regimen to fight exercise-induced fatigue.

Heparanase confers temozolomide resistance by regulation of exosome secretion and circular RNA composition in glioma.

Temozolomide (TMZ) resistance is the main challenge in the management of glioma patients. Heparanase can mediate the secretion and function of exosomes, which are considered to be a promising molecular delivery system for cancer therapy. Therefore, this study aimed to investigate whether heparanase-mediated delivery of exosomes was related to TMZ resistance of glioma. Heparanase was upregulated in TMZ-resistant glioma cells, and overexpression of heparanase led to increased resistance of U87 cells to TMZ. Knockdown of heparanase led to increased sensitivity of TMZ-resistant U251 cells (U251R) cells to TMZ. Heparanase promoted the secretion of exosomes from glioma cells, and coculture with exosomes derived from heparanase knockdown U251R cells partly restored the sensitivity of U251 cells to TMZ compared with exosomes derived from si-control transfected U251R cells. It was identified by circular RNA microarrays that hsa_circ_0042003 was upregulated in exosomes derived from U251R, which could be positively regulated by heparanase. U251R cell-derived exosomal hsa_circ_0042003 conferred the resistance of U251 cells to TMZ. In vivo studies also showed that U251R cell-derived exosomes induced resistance of U251 cells to TMZ, and the combination of tail-injected exosomal si-heparanase or exosomal si-hsa_circ_0042003 and intraperitoneal TMZ applied to nude mice abolished TMZ resistance. Heparanase mediated the transfer of exosomal hsa_circ_0042003 from TMZ-resistant glioma cells to drug-sensitive cells, which contributed to the chemoresistance of glioma to TMZ.

The use of acupuncture for advanced cancer care: Protocol for a systematic review and meta-analysis.

AIM: To assess the up-to-date evidence of acupuncture for the management of cancer-related and cancer treatment-related outcomes among people with advanced cancer. DESIGN: Systematic review with meta-analyses involving multidimensional outcomes. METHODS: The protocol of this systematic review has been registered in PROSPERO with the registration number CRD42020212982. Six databases (including Pubmed, EMBASE, Cochrane Library, SinoMed, ClinicalTrials.gov and Chinese Clinical Trial Registry) will be searched from inception through November 2020 to identify relevant interventional trials examining acupuncture management on multidimensional outcomes in patients with advanced cancer. Main outcomes will include cancer and treatment-related symptoms, quality of life, sleep quality and adverse events. DerSimonian & Laird random-effects meta-analysis will be applied to calculate pooled relative risks for binary data and pooled weighted mean differences (WMDs) or standardized mean differences (SMDs) for continuous data. Trial quality ratings and risk of bias will be evaluated using the Cochrane Risk of Bias Tool and the Grading of Recommendations Assessment, Development and Evaluation approach. DISCUSSION: The efficacy of acupuncture on advanced cancer care and outcomes has not yet been determined. Palliative care for patients with advanced cancer may involve multiple challenges that include physical and mental health care. This systematic review will offer updated and comprehensive evidence of acupuncture on specific outcomes induced by advanced cancer and cancer-related treatment, which can give high level clinical recommendations to improve patient care and clinical outcomes.

Rapid rehabilitation technique with integrated traditional Chinese and Western medicine promotes postoperative gastrointestinal function recovery.

BACKGROUND: During the perioperative period, the characteristic therapy of traditional Chinese medicine is effective in improving postoperative rehabilitation. In large-scale hospitals practicing traditional Chinese medicine, there is accumulating experience related to the promotion of fast recovery in the perioperative period. AIM: To evaluate the efficacy and safety of Yikou-Sizi powder hot compress on Shenque acupuncture point combined with rapid rehabilitation technique. METHODS: This prospective, multicenter, randomized, controlled study included two groups: Treatment group and control group. The patients in the treatment group and control group received Yikou-Sizi powder hot compress on Shenque acupuncture point combined with rapid rehabilitation technique and routine treatment, respectively. Clinical observation regarding postoperative recovery of gastrointestinal function was performed, including the times to first passage of flatus, first defecation, and first normal bowel sounds. The comparison between groups was conducted through descriptive analysis, χ 2, t, F, and rank-sum tests. RESULTS: There was a statistically significant difference in the time to postoperative first defecation between the treatment and control group (87.16 ± 32.09 vs 109.79 ± 40.25 h, respectively; P < 0.05). Similarly, the time to initial recovery of bowel sounds in the treatment group was significantly shorter than that in the control group (61.17 ± 26.75 vs 79.19 ± 33.35 h, respectively; P < 0.05). However, there was no statistically significant difference in the time to initial exhaust between the treatment and control groups (51.54 ± 23.66 vs 62.24 ± 25.95 h, respectively; P > 0.05). The hospitalization expenses for the two groups of patients were 62283.45 ± 12413.90 and 62059.42 ± 11350.51 yuan, respectively. Although the cost of hospitalization was decreased in the control group, the difference was not statistically significant (P > 0.05). This clinical trial was safe without reports of any adverse reaction or event. CONCLUSION: The rapid rehabilitation technique with integrated traditional Chinese and Western medicine promotes the recovery of postoperative gastrointestinal function and is significantly better than standard approach for patients after colorectal surgery.

Metabolomics Analysis of Laparoscopic Surgery Combined with Wuda Granule to Promote Rapid Recovery of Patients with Colorectal Cancer Using UPLC/Q-TOF-MS/MS.

Surgery is the primary curative treatment for patients with nonmetastasized colorectal cancer (CRC). Rate of complications, morbidity, mortality, and overall survival of patients with CRC are factors associated with speed of recovery following surgery. Wuda granule (WD) is a traditional Chinese medicine (TCM) prescription used to promote rapid recovery after surgery. However, the specific mechanism of action of WD has not been characterized. Our study included 60 patients with clear histopathological evidence of colon or rectal cancer who underwent CRC laparoscopic surgery and 30 healthy individuals. Serum biochemistry and clinical evaluation of gastrointestinal function showed that WD could improve the nutritional status and gastrointestinal function and reduce the level of inflammation of patients with CRC following laparoscopic surgery. In addition, we used UPLC/Q-TOF-MS/MS-based metabolomics analysis to determine the mechanism of WD-related rapid recovery following laparoscopic surgery in patients with CRC. Twenty metabolites associated with arachidonic acid, alanine, aspartate and glutamate, α-linolenic acid, pyruvate, histidine, and glycerophospholipids were identified. The results suggested that the therapeutic mechanism of laparoscopic surgery combined with WD may be related to regulation of nutritional status, inflammation, immune function, energy, and gastrointestinal function in patients with CRC. This study also highlighted the ability of TCM compounds to interact with multiple targets to induce synergistic effects. This study may result in further studies of WD as a therapeutic agent to promote recovery following surgical resection of CRC tumors.

Wuda granule, a traditional Chinese herbal medicine, ameliorates postoperative ileus by anti-inflammatory action.

BACKGROUND: Postoperative ileus (POI) is a temporary disturbance in gastrointestinal motility following surgery, and intestinal inflammatory response plays a critical role in the pathogenesis of POI. Wuda granule (WDG), a gastrointestinal prokinetic Chinese herbal medicine, is prescribed to promote recovery of gastrointestinal function after abdominal surgery. However, it has remained unclear whether WDG shows anti-inflammatory effects in POI. In the present study, we investigated the effects of WDG in a rat POI model and attempted to clarify the detailed mechanisms of action. METHOD: Experimental POI was induced in adult male SD rats by intestinal manipulation (IM). WDG were orally administered after surgery at the same points (6 h, 12 h, 18 h, 24 h). Histological changes of mesenterium, levels of cytokines, and CD68 and iNOS expression were determined in rats treated or not with WDG. We also investigated the transcriptome profile of rats treated with WDG in a POI model. RESULTS: Experimental POI in rats was characterized by a marked intestinal and systemic inflammatory response. WDG significantly inhibited the infiltration of neutrophils and macrophages, reduced the levels of IL-6, and CRP, and inhibited protein expressions of CD68 and iNOS in mesentery. Comparison analysis showed that there are 1432 differentially expressed genes (DEGs) between the POI and CON sample, whereas 331 DEGs between the WDG -treated sample and the POI group. And 16 DEGs were shared by the POI vs CON and WDG vs POI groups, among which 6 hub genes associated with immune system processes were identified and verified. CONCLUSIONS: WDG treatment ameliorates the impaired gastrointestinal motility in the rat model of POI through inhibiting the inflammatory response of mesentery.

Miscarriage on Endometriosis and Adenomyosis in Women by Assisted Reproductive Technology or with Spontaneous Conception: A Systematic Review and Meta-Analysis.

BACKGROUND: In the past several years, there has been an increasing concern on miscarriage caused by endometriosis or adenomyosis. However, the results reported by different studies remain controversial. The present study is aimed at assessing the impact of endometriosis and adenomyosis on miscarriage. MATERIALS AND METHODS: Searches were carried out in PubMed, Embase, and the Cochrane library for studies published from inception until February 29, 2020. The investigators included studies that evaluated miscarriage risk in pregnant women with endometriosis or adenomyosis by assisted reproductive technology (ART), or with spontaneous conception (SC). Miscarriage (<28 weeks) was the primary outcome. The secondary outcomes were antepartum hemorrhage (APH), postpartum hemorrhage (PPH), preterm birth, low birthweight, placenta praevia, placental abruption, ectopic pregnancy, stillbirth, gestational diabetes, preeclampsia, and intrauterine growth restriction (IUGR). Endnote was used for the study collection, and the data analyses were carried out by two authors using Review Manager version 5.2. RESULTS: Thirty-nine studies, which is comprised of 697,984 women, were included in the present study. Miscarriage risk increased in women with endometriosis in SC (OR: 1.81, 95% CI: 1.44-2.28, I 2 = 96%) compared with those without endometriosis, while women with endometriosis who underwent ART had a similar miscarriage risk, when compared to those with tubal infertility (OR: 1.03, 95% CI: 0.92-1.14, I 2 = 0%). Compared with those without adenomyosis, women with adenomyosis had an augmented miscarriage risk in ART (OR: 2.81, 95% CI: 1.44-5.47, I 2 = 64%). Compared with those without endometriosis, women with endometriosis had higher odds of APH, PPH, preterm birth, stillbirth, and placenta praevia. No difference was observed in the incidence of ectopic pregnancy, placental abruption, pre-eclampsia, gestational diabetes, low birthweight, and IUGR. CONCLUSION: Women with endometriosis had an augmented miscarriage risk in SC and a similar miscarriage risk during ART. Adenomyosis was associated with miscarriage in pregnant women using ART.

Anti-Angiogenic Alternative and Complementary Medicines for the Treatment of Endometriosis: A Review of Potential Molecular Mechanisms.

Endometriosis is caused by the growth or infiltration of endometrial tissues outside of the endometrium and myometrium. Symptoms include pain and infertility. Surgery and hormonal therapy are widely used in Western medicine for the treatment of endometriosis; however, the side effects associated with this practice include disease recurrence and menopause, which can severely influence quality of life. Angiogenesis is the main biological mechanism underlying the development of endometriosis. Numerous natural products and Chinese medicines with potent anti-angiogenic effects have been investigated, and the molecular basis underlying their therapeutic effects in endometriosis has been explored. This review aims to describe natural products and compounds that suppress angiogenesis associated with endometriosis and to assess their diverse molecular mechanisms of action. Furthermore, this review provides a source of information relating to alternative and complementary therapeutic products that mediate anti-angiogenesis. An extensive review of the literature and electronic databases, such as the China National Knowledge Infrastructure, PubMed, and Embase, was conducted using the keywords 'endometriosis,' 'traditional Chinese medicine,' 'Chinese herbal medicine,' 'natural compounds,' and 'anti-angiogenic' therapy. Anti-angiogenic therapy is an emerging strategy for the treatment of endometriosis. Natural anti-angiogenic products and Chinese medicines provide several beneficial clinical effects, including pain relief. In this review, we summarize clinical trials and experimental studies of endometriosis using natural products and Chinese medicines. In particular, we focus on anti-angiogenic products and alternative and complementary medicines for the treatment of endometriosis and additionally examine their therapeutic efficacy and mechanisms of action. Anti-angiogenic natural products and/or compounds provide a new approach for the treatment of endometriosis. Future work will require randomized trials with larger numbers of subjects, as well as long-term follow-up to confirm the findings described here.