Bergapten attenuates hemorrhagic shock induced multi-organ injury by inhibiting NLRP3 inflammasome activation and pyroptosis.

OBJECTIVES: Treatment of hemorrhagic shock (HS) induced multi-organ injury remains a challenge. Bergapten (BeG) is a bioactive coumarin-derived compound, and previous articles have suggested that BeG may serve as a prospective therapeutic modality for HS. This study was designed to investigate the efficacy of BeG in the treatment of HS and its underlying mechanisms. METHODS: In this research, we established a rat model of HS, following which we assessed the protective effects of BeG on HS induced multi-organ injury. Subsequently, we scrutinized the activation of NLRP3 inflammasomes and pyroptosis in damaged organs. Additionally, we conducted examinations of AMPK and the downstream mitophagy pathway in damaged organs. Finally, we established a hypoxia/reoxygenation (H/R) model in HK-2 cells to simulate the in vitro HS process. Following AMPK inhibition with compound C, we evaluated the levels of mitophagy and cellular pyroptosis in BeG-treated HK-2 cells subjected to H/R. RESULTS: BeG treatment alleviated HS induced multi-organ injury. Subsequent analyses indicated that the therapeutic effects of BeG were related to the attenuation of NLRP3 inflammasome activation and pyroptosis. Additionally, we found BeG treatment stimulated the phosphorylation of AMPK, thereby enhancing mitophagy. Lastly, we found that the inhibition of AMPK in vitro attenuates BeG's enhancement of mitophagy and its suppression of pyroptosis. CONCLUSION: Our research indicates that BeG has the potential to alleviate multi-organ injury induced by HS. The protective effect of BeG is likely associated with its promotion of mitophagy through AMPK activation, thereby inhibiting NLRP3 inflammasome-mediated pyroptosis.

Comparative Different Interventions to Improve Exercise Adherence in Patients in the Postoperative Breast Cancer Phase of Care: A Network Meta-analysis.

BACKGROUND: Global Cancer Statistics 2020 reported that breast cancer had exceeded lung cancer as the most frequently diagnosed cancer. Surgery is the primary treatment modality for breast cancer, but postoperative upper limb dysfunction often occurs; functional exercise can alleviate this and restore upper limb function. However, exercise compliance is low in postoperative breast cancer patients; thus, many studies have been conducted in recent years to improve patient compliance with exercise. OBJECTIVE: The aim of this study was to compare the effectiveness of different interventions to improve exercise adherence in postoperative breast cancer patients. METHODS: We searched PubMed, Cochrane Library, Web of Science, EMBASE, Wan Fang, CNKI, VIP, and CBM databases for eligible studies. Exercise adherence rate and quality-of-life difference were assessed as outcomes. Sensitivity analysis and inconsistency detection were performed to evaluate whether the exclusion of high-risk studies affected the validity. Risk of bias was assessed using the risk-of-bias table in RevMan 5.4. Surface under the cumulative ranking was used to estimate the rankings among different interventions. RESULTS: Twenty-five randomized controlled trials involving 9 interventions were included, and the network meta-analysis results showed that patients in the pedometer + counseling group had the best exercise adherence. CONCLUSION: Pedometer + counseling care measures are recommended to improve exercise adherence in postoperative breast cancer patients. IMPLICATIONS FOR PRACTICE: Oncology nurses can improve patients' exercise compliance through counseling and by giving them pedometers to wear.

BMI-1 activates hepatic stellate cells to promote the epithelial-mesenchymal transition of colorectal cancer cells.

BACKGROUND: Activated hepatic stellate cells (aHSCs) are the major source of cancer-associated fibroblasts in the liver. Although the crosstalk between aHSCs and colorectal cancer (CRC) cells supports liver metastasis (LM), the mechanisms are largely unknown. AIM: To explore the role of BMI-1, a polycomb group protein family member, which is highly expressed in LM, and the interaction between aHSCs and CRC cells in promoting CRC liver metastasis (CRLM). METHODS: Immunohistochemistry was carried out to examine BMI-1 expression in LM and matched liver specimens of CRC. The expression levels of BMI-1 in mouse liver during CRLM (0, 7, 14, 21, and 28 d) were detected by Western blotting (WB) and the quantitative polymerase chain reaction (qPCR) assay. We overexpressed BMI-1 in HSCs (LX2) by lentivirus infection and tested the molecular markers of aHSCs by WB, qPCR, and the immunofluorescence assay. CRC cells (HCT116 and DLD1) were cultured in HSC-conditioned medium (LX2 NC CM or LX2 BMI-1 CM). CM-induced CRC cell proliferation, migration, epithelial-mesenchymal transition (EMT) phenotype, and transforming growth factor beta (TGF-ß)/SMAD pathway changes were investigated in vitro. A mouse subcutaneous xenotransplantation tumor model was established by co-implantation of HSCs (LX2 NC or LX2 BMI-1) and CRC cells to investigate the effects of HSCs on tumor growth and the EMT phenotype in vivo. RESULTS: Positive of BMI-1 expression in the liver of CRLM patients was 77.8%. The expression level of BMI-1 continued to increase during CRLM in mouse liver cells. LX2 overexpressed BMI-1 was activated, accompanied by increased expression level of alpha smooth muscle actin, fibronectin, TGF-ß1, matrix metalloproteinases, and interleukin 6. CRC cells cultured in BMI-1 CM exhibited enhanced proliferation and migration ability, EMT phenotype and activation of the TGF-ß/SMAD pathway. In addition, the TGF-ßR inhibitor SB-505124 diminished the effect of BMI-1 CM on SMAD2/3 phosphorylation in CRC cells. Furthermore, BMI-1 overexpressed LX2 HSCs promoted tumor growth and the EMT phenotype in vivo. CONCLUSION: High expression of BMI-1 in liver cells is associated with CRLM progression. BMI-1 activates HSCs to secrete factors to form a prometastatic environment in the liver, and aHSCs promote proliferation, migration, and the EMT in CRC cells partially through the TGF-ß/SMAD pathway.

The needs of women experiencing perinatal loss: A qualitative systematic review and meta-synthesis.

PROBLEM: There have been some studies on the needs of women experiencing perinatal loss in various socio-cultural contexts, but there is no research that systematically and comprehensively synthesizes these needs. BACKGROUND: Perinatal loss has profound psychosocial effects. The misconceptions and prejudices existing in the public, the lack of satisfactory clinical care, and the available social support may all increase the negative impact. AIM: To synthesize evidence for the needs of women experiencing perinatal loss, attempt to explain the findings, and provide insights into the application of evidence. METHODS: Published papers were searched in seven electronic databases until 26 March 2022. The Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research was used to assess the methodological quality of the included studies. Through meta-aggregation, the data was extracted, rated, and synthesized, resulting in new categories and findings. The credibility and dependability of the synthesized evidence were evaluated by ConQual. FINDINGS: Thirteen studies that fulfilled the inclusion criteria and quality assessment were included in the meta-synthesis. Five synthesized findings were identified, covering information needs, emotional needs, social needs, clinical care needs, as well as spiritual and religious needs. CONCLUSION: Women's perinatal bereavement needs were individualized and diverse. There is a necessity to understand, identify, and respond to their needs in a sensitive and personalized way. Families, communities, healthcare institutions, and society form a coordinated whole and provide accessible resources to improve recovery from perinatal loss and a satisfactory outcome in the subsequent pregnancy.

Clinical practice guidelines for perinatal bereavement care: A systematic quality appraisal using AGREE II instrument.

PURPOSE: This study aimed to evaluate and analyze the methodological quality of the published clinical practice guidelines (CPGs) for perinatal bereavement care and provide a reference for implementing best clinical practices. METHODS: We performed a systematic and comprehensive search in five electronic databases (PubMed, The Cochrane Library, Web of Science, CNKI, Wan Fang Database), eight guideline databases, and six websites of professional organizations from March 2021 to June 2021. Four researchers used the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument to appraise the selected CPGs independently. The inter-rater reliability of AGREE II domains was calculated using the intraclass correlation coefficient with 95% CI. RESULTS: We included a total of 8 CPGs. The mean scores of six domains ranged from the lowest score of 46.61% (editorial independence) to the highest score of 87.85% (clarity of presentation). Subgroup analysis showed no statistical difference. Each domain achieved "good" and "very good" intraclass reliability. Two CPGs were deemed as grade A (strongly recommended), five were rated as grade B (recommended with modifications), and one was evaluated as grade C (not recommended). CONCLUSIONS: Healthcare professionals in obstetrics and neonatology play an important role in helping bereaved parents and families to cope with perinatal loss. High-quality CPGs for perinatal bereavement care can serve as useful resources to improve the quality and outcomes of clinical practice. More efforts should be made to disseminate the best practices for perinatal bereavement care. When implementing GCPs in countries or regions with different backgrounds, professional translations, strict validations, and cultural adaptations should be taken into account.

Targeting BMI-1-mediated epithelial-mesenchymal transition to inhibit colorectal cancer liver metastasis.

Liver is the most common metastatic site for colorectal cancer (CRC), there is no satisfied approach to treat CRC liver metastasis (CRCLM). Here, we investigated the role of a polycomb protein BMI-1 in CRCLM. Immunohistochemical analysis showed that BMI-1 expression in liver metastases was upregulated and associated with T4 stage, invasion depth and right-sided primary tumor. Knockdown BMI-1 in high metastatic HCT116 and LOVO cells repressed the migratory/invasive phenotype and reversed epithelial-mesenchymal transition (EMT), while BMI-1 overexpression in low metastatic Ls174T and DLD1 cells enhanced invasiveness and EMT. The effects of BMI-1 in CRC cells were related to upregulating snail via AKT/GSK-3ß pathway. Furthermore, knockdown BMI-1 in HCT116 and LOVO cells reduced CRCLM using experimental liver metastasis mice model. Meanwhile, BMI-1 overexpression in Ls174T and DLD1 significantly increased CRCLM. Moreover, sodium butyrate, a histone deacetylase and BMI-1 inhibitor, reduced HCT116 and LOVO liver metastasis in immunodeficient mice. Our results suggest that BMI-1 is a major regulator of CRCLM and provide a potent molecular target for CRCLM treatment.

Sodium butyrate modulates gut microbiota and immune response in colorectal cancer liver metastatic mice.

Colorectal cancer (CRC) liver metastasis (CLM) is the leading death cause of CRC patients, but there is no satisfied approach to treat CLM. Gut microbiota plays a pivotal role in CRC initiation and development. Targeting dysbiosis of the gut microbiota might open up new opportunities for CLM treatment. Here, we investigated the efficacy of sodium butyrate (NaB), a major product of gut microbial fermentation, in modulating gut microbiota in CLM mice. NaB supplement decreased mouse colon cancer CT26 cell liver metastasis in intrasplenic tumor injection model of BALB/c mice. Using 16S rRNA gene sequencing, we found altered microbiota composition in CLM mice, characterized by increases of Firmicutes and Proteobacteria. NaB beneficially changed dysbiosis in CLM mice. Functional analysis of the KEGG pathways showed that NaB changed pathways related to immune system diseases and primary immunodeficiency in CLM mice. In addition, NaB decreased T regulatory cells and increased natural killer T cells and T helper 17 cells, accordingly decreased IL-10 and increased IL-17 secretion in CLM mice liver. In conclusion, NaB beneficially modulated gut microbiota and improved host immune response in CLM mice. These findings demonstrate the therapeutic potential of NaB in CLM treatment.

MicroRNA-30b-5p functions as a metastasis suppressor in colorectal cancer by targeting Rap1b.

Colorectal liver metastasis (CRLM) is the leading cause of death in patients with colorectal cancer (CRC). MiR-30b-5p can function as an oncogene or tumor suppressor in cancers, but its role in CRLM is still unknown. Here, we found that miR-30b-5p overexpression suppressed the invasion, migration, adhesion, and motility of HCT116 and LoVo cells. The expression of EMT (Zeb1, Snail, and vimentin) and adhesion-related proteins (p-paxillin and p-Src) was decreased. We validated Rap1b, a Ras family small GTPase that regulates cell adhesion and mobility, as the direct and functional target of miR-30b-5p. Rap1b overexpression rescued the aggressive characteristics of CRC cells that were inhibited by miR-30b-5p. Rap1b knockdown suppressed invasion and migration and decreased CRC cell-matrix adhesion and spreading, which was consistent with the results of miR-30b-5p overexpression. Further in vivo experiments demonstrated that miR-30b-5p overexpression inhibited CRLM, but Rap1b rescue attenuated the inhibitory effect of miR-30b-5p. In addition, miR-30b-5p was downregulated in CRC specimens, and Rap1b showed a negative correlation with miR-30b-5p expression in primary CRC and LM tissues. These results indicate that miR-30b-5p functions as a metastasis suppressor by targeting Rap1b and may provide a new target for the treatment of CRLM.

[Epidemiological survey on the infection of Paragonimus westermani in Jiangxi Province].

OBJECTIVE: To investigate Paragonimus westermani infection in the intermediate hosts and animal reservoivs in Jiangxi Province. METHODS: Two forest farms in Jingan and Wanzai Counties and one town in Yushan County of Jiangxi Province were selected as pilots for epidemiological and retrospective survey. The intermediate hosts (snails, crabs) and reservoir hosts (cat, dog, civet cat, wildcat, etc.) were collected and examined. Data on the changes of ecological environment and people's behaviors were also collected. RESULTS: The average infection rate in Semisulcospira libertina and Sinopotamon spp. was 0.21% and 54.3% respectively, and that of reservoir hosts was 5.6%. Compared with those in 20 years ago, the infection rate in Sinopotamon spp. decreased considerably. CONCLUSION: The three areas are still endemic for P. westermani with lower prevalence than before possibly due to the change of ecological environment.