Specneuzhenide improves bleomycin-induced pulmonary fibrosis in mice via AMPK-dependent reduction of PD-L1.

BACKGROUND: Pulmonary fibrosis (PF) is an escalating global health issue, characterized by rising rates of morbidity and mortality annually. Consequently, further investigation of potential damage mechanisms and potential preventive strategies for PF are warranted. Specnuezhenide (SPN), a prominent secoiridoid compound derived from Ligustrum lucidum Ait, exhibits anti-inflammatory and anti-oxidative capacities, indicating the potential therapeutic actions on PF. However, the underlying mechanisms of SPN on PF remain unclear. PURPOSE: This work was aimed at investigating the protective actions of SPN on PF and the potential mechanism. METHODS: In vivo, mice were administrated with bleomycin (BLM) to establish PF model. PF mice were treated with SPN (45/90 mg/kg) by gavage. In vitro, we employed TGF-ß1 (10 ng/mL)-induced MLE-12 and PLFs cells, which then were treated with SPN (5, 10, 20 µM). DARTS assay, biofilm interference experiment and molecular docking were performed to investigate the molecular target of SPN. RESULTS: In vivo, we found SPN treatment improved survival rate, alleviated pathological changes through reducing BLM-induced extracellular matrix (ECM) deposition, as well as BLM-induced epithelial-mesenchymal transition (EMT). In vitro, SPN inhibited EMT and lung fibroblast transdifferentiation. Mechanistically, SPN activated the AMPK protein to decrease the abnormally high level of PD-L1. Furthermore, the compound C, known as an AMPK inhibitor, exhibited a significant hindrance to the inhibition of SPN on TGF-ß1-caused fibroblast transdifferentiation and proliferation. This outcome could be attributed to the fact that compound C could eliminate the inhibitory effects of SPN on PD-L1 expression. Interestingly, DARTS assay, biofilm interference experiment and molecular docking results all indicated that SPN could bind to AMPK, which suggested that SPN might be a potential agonist targeting AMPK protein. CONCLUSION: Altogether, the results in our work illustrated that SPN promoted AMPK-dependent reduction of PD-L1 protein, contributing to the inhibition of fibrosis progression. Thus, SPN may represent a potential AMPK agonist for PF treatment.

Cerebral neurotoxicity of amino-modified polystyrene nanoplastics in mice and the protective effects of functional food Camellia pollen.

Accumulating evidence suggests that nanoplastics contribute to an increased risk of brain damage, however, the precise underlying mechanisms remain unclear. Here, we subjected mice to long-term exposure to amino-modified polystyrene nanoplastics (APS-NPs). These nanoplastics were detected in the mouse brain; coupled with the observed upregulation of Alzheimer's disease-associated genes (APP and MAPT). To further explore nanoplastic damage mechanisms and the corresponding protective strategies against these mechanisms in vitro, we used hCMEC/D3 and HT22 cells. Results showed that APS-NPs disrupted tight junction proteins (Occludin and ZO-1) via TLR2/MMP9 axis, resulting in blood-brain barrier permeation; this was significantly mitigated by functional food Camellia pollen treatment. APS-NPs initiated iNOS and nNOS upregulation within neurons resulting in Sirtuin 1 deacetylase inactivation and CBP acetyltransferase stimulation, ultimately leading to Ac-Tau formation. This process was attenuated by Camellia pollen, which also ameliorated the APS-NPs-induced neuronal apoptosis mediated by the p53/Bax/Bcl-2 axis. Network pharmacology analysis of Camellia pollen offered a further theoretical understanding of its potential applications in preventing and treating nervous system disorders, such as Alzheimer's disease. This study established that Camellia pollen protects the brain against APS-NPs-mediated blood-brain barrier damage and alleviates neuronal apoptosis and Alzheimer's disease-like neurotoxicity. This study elucidates the mechanisms underlying polystyrene-induced brain damage and can be used to inform future prevention and treatment strategies.

"Typhoidal Cells" Appear in a Woman with Hemophagocytic Syndrome Secondary To Brucellosis: A Case Report.

We report a case of hemophagocytic syndrome (HPS) secondary to brucellosis, in which typhoidal cells were found in bone marrow, suggesting typhoidal cells present not only in Salmonella typhi infections but also in other bacterial infections. Typhoidal cells in bone marrow can be used to quickly identify the presence of bacterial infection pending the results of bone marrow and/or blood cultures.

Role of ANO1 in tumors and tumor immunity.

Dysregulation of gene amplification, cell-signaling-pathway transduction, epigenetic and transcriptional regulation, and protein interactions drives tumor-cell proliferation and invasion, while ion channels also play an important role in the generation and development of tumor cells. Overexpression of Ca2+-activated Cl- channel anoctamin 1 (ANO1) is shown in numerous cancer types and correlates with poor prognosis. However, the mechanisms involved in ANO1-mediated malignant cellular transformation and the role of ANO1 in tumor immunity remain unknown. In this review, we discuss recent studies to determine the role of ANO1 in tumorigenesis and provide novel insights into the role of ANO1 in the context of tumor immunity. Furthermore, we analyze the roles and potential mechanisms of ANO1 in different types of cancers, and provide novel notions for the role of ANO1 in the tumor microenvironment and for potential use of ANO1 in clinical applications. Our review shows that ANO1 is involved in tumor immunity and microenvironment, and may, therefore, be an effective biomarker and therapeutic drug target.

Prognostic significance of ANO1 expression in cancers.

BACKGROUND: Anoctamin-1 (ANO1) plays a pivotal role in cancer progression. A meta-analysis was conducted to assess the potential prognostic role of ANO1 in cancers. METHODS: A total of 1760 patients from 7 eligible studies were included into the analysis. Pooled hazard ratios or odds ratios were extracted and calculated with a random-effects model, and analyses of heterogeneity bias were conducted. RESULTS: Our results showed that over expression of ANO1 was significantly correlated with poor overall survival in all cancers (HR = 1.52; 95% CI: 1.19-1.92; P = .0006). Subgroup analysis indicated that there was a significant association between over expression of ANO1 and poor prognosis breast cancer (HR = 3.24; 95% CI: 1.74-6.04), head and neck squamous cell carcinoma (HR = 1.14; 95% CI: 1.00-1.30), esophageal squamous cell carcinoma (HR = 1.93; 95% CI: 1.07-3.50), gastric cancer (HR = 1.62; 95% CI: 1.12-2.34) and colorectal cancer (HR = 1.38; 95% CI: 1.03-1.85). In addition, over expression of ANO1 was not associated with TNM stage, histological grade, lymph node metastasis, tumor size, age and gender. However, ANO1 was significantly associated with human epidermal growth factor receptor 2, but not associated with progesterone receptor or estrogen receptor in breast cancer. CONCLUSIONS: Our results indicate that ANO1 can be a predictive factor for prognosis of cancer.

Clinical usefulness of high levels of C-reactive protein for diagnosing epithelial ovarian cancer.

The purpose of the present study was to evaluate the diagnostic role of CRP in ovarian cancer and to assess whether CRP can be combined with tumor markers to enhance the diagnostic efficacy toward ovarian cancer. Area under the curve, sensitivity, and specificity were calculated to access the diagnostic ability of each singly and combined as markers for ovarian cancer. The CRP cut-off value was then calculated to evaluate the diagnostic efficacy of CRP for ovarian cancer. Our results showed that values for all markers were significantly higher in the cancer group than in the control group. Receiver operating characteristic curve results showed that CA125 had the highest diagnostic efficacy for ovarian cancer, while the sensitivity for CRP was higher than for CA125, and the specificity for CRP was equal to that of CA125. The combination of CRP, CA125, and HE4, however, provided the strongest diagnostic capability. Furthermore, the diagnostic cut-off value for CRP with regard to ovarian cancer was 9.8 mg/L, and high levels of CRP were correlated with stage and tumor size of ovarian cancer. Our study indicated that CRP is valuable in the diagnosis of ovarian cancer, and that combining CRP with CA125 and HE4 improved the diagnostic efficacy with respect to ovarian cancer.

Detection of ANO1 mRNA in PBMCs is a promising method for GISTs diagnosis.

ANO1 is a calcium-activated chloride channel protein that has been used to diagnose GISTs after tissue biopsy. Recently, ANO1 mRNA amplification in the blood has received considerable attention as a useful method for the diagnosis of GISTs. The aim of this study was to evaluate the diagnostic ability of ANO1 mRNA in distinguishing GIST patients from healthy subjects. We constructed a logistic regression model for examining the diagnostic ability of ANO1 mRNA in comparison with conventional tumor markers, including CEA, CA199, and CA724. Our results showed that ANO1 mRNA was significantly amplified in PBMCs, the average expression level and range of ANO1 mRNA in the blood were increased along with the expression of ANO1 in the tissues, and the extent of amplification of ANO1 was associated with tumor size. In addition, ROC curve analysis showed that ANO1 mRNA in the blood had the highest specificity when compared with conventional tumor markers. Moreover, a combined analysis with ANO1 mRNA and conventional tumor markers had the highest sensitivity in diagnosing GISTs. Our study indicated that detection of ANO1 mRNA in PBMCs is a promising method for diagnosis of GISTs in vitro.

Rural domestic waste management in Zhejiang Province, China: Characteristics, current practices, and an improved strategy.

UNLABELLED: Lack of access to adequate sanitation facilities has serious health implications for rural dwellers and can degrade the ecosystems. This study offers a systemantic and quantitative overview of historical data on rural domestic waste (RDW) production and past and current management practices in a prototype region in China, where rural areas are undergoing rapid urbanization and are confronted with great environmental challenges associated with poor RDW management practices. The results indicate that RDW is characterized with a large fraction of kitchen waste (42.9%) and high water content (53.4%). The RDW generation (RDWG) per capita between 2012 and 2020 is estimated to increase from 0.68 to 1.01 kg/d-cap. The Hill 1 model is able to adequately simulate/project the population growth in a rural area from 1993 to 2020. The annual RDWG in the region is estimated to double from 6,033,000 tons/year in 2008 to 12,030,000 tons/year by 2020. By comparing three RDW management scenarios based on the life-cycle inventory approach and cost-benefit analysis, it is strongly recommended that the present Scenario 2 (sanitary landfill treatment) be upgraded to Scenario 3 (source separation followed by composting and landfill of RDW) to significantly reduce the ecological footprint and to improve the cost-effectiveness and long-term sustainability. IMPLICATIONS: Rural domestic waste (RDW) is affecting 720 million people in China and more than 3221 million people worldwide. Consequently, handling and disposal of RDW have serious health implications to rural dwellers and the ecosystems. This study offers a systemantic and quantitative overview and analysis of historical data on RDW production and management practices in a prototype region in China, which is confronted with great environmental challenges associated with RDW. Then we predict future production of RDW and propose a sustainable RDW management strategy, which holds the promise of greatly mitigating the mounting environmental pressure associated with RDW and provides science-based guidance for decision makers and practitioners for assuring rapid yet "green" economic development.

[The extraction and identification of total flavanone from longan pericarp].

OBJECTIVE: In order to make use of the resources of total flavanone in pericarp of longan. METHODS: The flavonids were extracted with ethanol. Used spectrophotometry to check the flavanone. RESULTS: The total flavanone in the pericarp was 1.101 mg/ml and the rate of recovery was 99.98%. CONCLUSION: The extraction and purifying methods in this experiment can get the outcome and the purity of the flavanone very high. This method is a purely physical process and has not any pollution. It is an ideal way to extract the flavanone of longan skin.