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The escalating obesity epidemic and aging population have propelled metabolic dysfunction-associated steatohepatitis (MASH) to the forefront of public health concerns. The activation of FXR shows promise to combat MASH and its detrimental consequences. However, the specific alterations within the MASH-related transcriptional network remain elusive, hindering the development of more precise and effective therapeutic strategies. Through a comprehensive analysis of liver RNA-seq data from human and mouse MASH samples, we identified central perturbations within the MASH-associated transcriptional network, including disrupted cellular metabolism and mitochondrial function, decreased tissue repair capability, and increased inflammation and fibrosis. By employing integrated transcriptome profiling of diverse FXR agonists-treated mice, FXR liver-specific knockout mice, and open-source human datasets, we determined that hepatic FXR activation effectively ameliorated MASH by reversing the dysregulated metabolic and inflammatory networks implicated in MASH pathogenesis. This mitigation encompassed resolving fibrosis and reducing immune infiltration. By understanding the core regulatory network of FXR, which is directly correlated with disease severity and treatment response, we identified approximately one-third of the patients who could potentially benefit from FXR agonist therapy. A similar analysis involving intestinal RNA-seq data from FXR agonists-treated mice and FXR intestine-specific knockout mice revealed that intestinal FXR activation attenuates intestinal inflammation, and has promise in attenuating hepatic inflammation and fibrosis. Collectively, our study uncovers the intricate pathophysiological features of MASH at a transcriptional level and highlights the complex interplay between FXR activation and both MASH progression and regression. These findings contribute to precise drug development, utilization, and efficacy evaluation, ultimately aiming to improve patient outcomes.
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Hereditary angioedema (HAE) is a rare autosomal genetic disease for which there are currently nine FDA-approved drugs. This review summarizes drug treatments for HAE based on four therapeutic pathways: inhibiting the contact system, inhibiting bradykinin binding to B2 receptors, supplying missing C1 inhibitors, and inhibiting plasminogen conversion. The review generalizes the clinical use, pharmacological effects and mechanisms of HAE drugs, and it also discusses possible development directions and targets to enhance understanding of HAE and help researchers.
Subject(s)
Angioedemas, Hereditary , Humans , Angioedemas, Hereditary/drug therapy , Angioedemas, Hereditary/genetics , Angioedemas, Hereditary/metabolismABSTRACT
Vaccariae Semen, derived from the dried ripe seed of Vaccaria segetalis (Neck.) Garcke, has various therapeutic characteristics in traditional Chinese medicine (TCM), containing promoting blood circulation and unblocking meridians. It exhibits significant anti-cancer activity and is therapeutically utilized to treat and reduce chemotherapy adverse effects in cancer patients, notably those with lung cancer. However, the active ingredients responsible for its anti-lung cancer efficacy remain unknown. In this study, we used A549 cell fishing in conjunction with UHPLC-LTQ Orbitrap MS to screen for anti-lung cancer active components in Vaccariae Semen. The cell counting Kit-8 (CCK-8) assay revealed that the n-butanol extract substantially reduced A549 cell growth. Through the cell fishing assay, we found 14 A549 cell-binding compounds in the n-butanol extract, all of which were identified as triterpenoid saponins. The total saponins of Vaccariae Semen were subsequently purified using macroporous adsorption resin (MAR), and they showed a significant inhibitory effect on the proliferation of A549 lung cancer cells, as well as alterations in cell morphology, apoptosis, and fragmentation. In conclusion, saponins were discovered as the key active components responsible for the anti-lung cancer activity of Vaccariae Semen.
Subject(s)
Early Detection of Cancer , Lung Neoplasms , Humans , 1-Butanol , A549 Cells , Chromatography, High Pressure Liquid , Lung Neoplasms/drug therapy , SeedsABSTRACT
INTRODUCTION: Citri Sarcodactylis Fructus has the effects of relieving cough, removing phlegm, and reducing asthma, but little is known about the metabolic and distribution of its chemical constituents in vivo. Therefore, it is necessary to study the metabolism of Citri Sarcodactylis Fructus in vivo. OBJECTIVE: We aimed to (1) analyze the distribution of prototype compounds and metabolites of the chemical constituents of Citri Sarcodactylis Fructus in rat and (2) infer the metabolites and metabolic pathways of the chemical constituents. MATERIALS AND METHODS: A C18 column (3 × 100 mm, 2.6 µm) was used. The mobile phase was water containing 0.1% formic acid (eluent A) and acetonitrile containing 0.1% formic acid (eluent B) at a discharge rate of 0.3 mL/min. Mass spectra of biological samples were collected in electrospray ionization (ESI) positive ion mode in the m/z 100-1500 scan range. The obtained biological samples were then subjected to chemical analysis, including plasma, urine, feces, and heart, liver, spleen, lungs, kidneys, stomach, and small intestine tissues. Prototype compounds and metabolites were identified. RESULTS: In all, 40 prototype compounds and 78 metabolites, including 26 phase I metabolites and 52 phase II metabolites, were identified using UHPLC-Q/Orbitrap HRMS. Eight possible metabolic pathways (reduction, hydrolysis, dehydration, methylation, hydroxylation, sulfation, glucuronidation, and demethylation) were proposed. The prototype compounds were predominantly distributed in lung tissues. The metabolites were mainly distributed in plasma and kidney tissues. CONCLUSION: We systematically investigated the metabolites of Citri Sarcodactylis Fructus in vivo. We suggest metabolic pathways that might be relevant for further metabolic studies and screening of active ingredients of Citrus Sarcodactylis Fructus in vivo.
Subject(s)
Drugs, Chinese Herbal , Rats , Animals , Chromatography, High Pressure Liquid , Formates , Tandem Mass SpectrometryABSTRACT
Objective: The aim of this study was to explore the correlation and difference of influencing factors by analyzing the psychological status of patients with cervical precancerous lesions and cancer in Han and Ethnic minorities. So as to provide evidence for more targeted psychological intervention for categories types of patients. Methods: The Chinese version of Kessler 10 scale was used to investigate 200 Han Chinese patients with cervical lesions and 100 ethnic minority patients with cervical lesions in Yunnan Cancer Center. Statistical analysis was performed using t-test, analysis of variance, and multivariable linear regression. Results: There was no significant difference in the distribution of demographic characteristics between the two groups (P > 0.05).The results of univariate analysis showed that the impression of K10 score was statistically significant among the following factors: educational level, awareness of HPV vaccine, disease screening status, employee medical insurance, economic burden of disease, cancerous or not, pathological type, treatment modalities, marital status, and family genetic history of tumor (P < 0.05). After multivariate analysis and considering the influence of the number of independent variables, it indicates that the economic burden of the disease, occupation, and family genetic history of tumor had a greater impact on the total score of Han patients among many factors, accounting for a total of 8.1%(Adj R2 = 0.081).Treatment modalities had the greatest effect on the scores of ethnic minority patients, accounting for 8.4%(Adj R2 = 0.084). Conclusion: The factors affecting the psychological status of patients between the two groups have similarities and differences. Multifactorial analysis showed that the main factors affecting the psychology of Han patients were: economic burden caused by the disease, occupation, and family genetic history of tumor; while the main factors affecting the psychology of minority patients were: treatment modalities. Therefore, targeted recommendations and policy measures can be proposed respectively.
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BACKGROUND: Cervical cancer is the fourth most diagnosed cancer and the leading cause of cancer death, and it still poses a crippling threat to women's health. China launched the National Cervical Cancer Screening Program for Rural Women in 2009, and an increasing number of cervical cancer patients have been detected. Health-related quality of life is not only the end point of cancer research but is also related to socioeconomic and clinical factors and has received an increasing amount of attention. In light of the characteristics of the Yunnan nationality, we conducted cross-sectional research to assess and explore the health-related quality of life in both Han and ethnic minority patients. METHODS: A cross-sectional study was conducted from January 2020 to May 2021 at the Third Affiliated Hospital of Kunming University/Yunnan Cancer Hospital. Patients, including 100 Han patients and 100 ethnic minorities, were interviewed using the FACT-Cx questionnaire within 3 months of receiving treatment. RESULTS: Patients of Han ethnicity and ethnic minorities were comparable in both sociodemographic and clinical features. The total FACT-Cx scores were 139.38 ± 9.83 and 134.39 ± 13.63 in Han and ethnic minority patients, respectively (P < 0.05). Significant differences were shown in physical well-being, emotional well-being and the FACT-Cx subscale between the Han and ethnic minority groups. Independent predictors of the FACT-Cx scale were ethnicity, educational level, participation in the National Cervical Cancer Screening Program for Rural Areas (NCCSPRA) and clinical stage. CONCLUSIONS: The results of our study imply that the HRQOL of Han patients is better than that of ethnic minority patients. Thus, clinicians and related health workers should pay more attention to the HRQOL of cervical cancer patients, especially for ethnic minority patients, and provide psychosocial interventions as much as possible to improve their HRQOL. Policies should also aim to strengthen health education regarding cervical cancer and expand the coverage of the NCCSPRA among those who are ethnic minorities, are older and have low educational levels.
Subject(s)
Ethnicity , Uterine Cervical Neoplasms , Humans , Female , Ethnicity/psychology , China , Minority Groups , Ethnic and Racial Minorities , Cross-Sectional Studies , Quality of Life/psychology , Early Detection of CancerABSTRACT
Introduction: This study aimed to investigate the effect of androgen on bone metabolism in hyperuricemic rats. Material and methods: Forty male Wistar rats were randomly divided into four groups: sham operation group, simple hyperuricemic group, hyperuricemic castration group, and simple castration group. A rat model of chronic hyperuricemia was established using potassium oxonate and ethambutol. Blood was sampled from the vena angularis at week 0, 4, 6, 8 and 12 after surgery to detect for uric acid, calcium, phosphorus and alkaline phosphatase, and investigate the effect of androgen on bone metabolism in hyperuricemic rats. Results: From the 4th week, compared with the sham operation group, the differences in uric acid levels between the simple hyperuricemic group and hyperuricemia castration group were statistically significant (p < 0.05), suggesting the successful establishment of the model of hyperuricemia. At the 6th week, uric acid levels decreased in the two hyperuricemic groups, and the difference from the sham operation group decreased (p = 0.05), showing that the modeling method had deteriorated. At the 8th week, the differences in uric acid levels between the two castration groups and sham operation group were statistically significant (p < 0.05). At the 12th week, the differences in serum levels of phosphorus between the simple hyperuricemic group and hyperuricemic castration group were statistically significant (p < 0.05). Conclusions: Androgen can induce bone metabolism changes in rats with hyperuricemia.
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BACKGROUND: As one of the most common tumors, gastric cancer (GC) has a high mortality rate, since current examination approaches cannot achieve early diagnosis. Fusobacterium nucleatum (Fn) primarily colonized in the oral cavity, has been reported to be involved in the development of gastrointestinal tumor. Until now, little is known about the relationship between salivary Fn and GC. AIM: To determine whether salivary Fn could be a biomarker to diagnose GC and explore the influence of Fn on GC cells. METHODS: The abundance of Fn in saliva was quantified by droplet digital polymerase chain reaction in 120 GC patients, 31 atrophic gastritis (AG) patients, 35 non-AG (NAG) patients, 26 gastric polyp (GP) patients, and 20 normal controls (NC) from Qilu Hospital of Shandong University from January 2019 to December 2020. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of Fn as well as traditional serum tumor markers, including carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and CA72-4. Transwell assay and wound-healing assay were conducted to assess the influence of Fn infection on GC cells. The expression of epithelial-mesenchymal transition (EMT) markers was detected using western blot assay. RESULTS: We found that the level of salivary Fn in GC patients was significantly increased compared with those in AG, NAG, and GP patients and NC (P < 0.001). ROC curve analysis showed a favorable capability of Fn (73.33% sensitivity; 82.14% specificity; area under the curve: 0.813) in GC diagnosis, which was superior to that of CEA, CA19-9, CA72-4, ferritin, and sialic acid. The Fn level in saliva of GC patients was increased as the TNM stage increased. GC patients with lymph node metastasis had higher Fn levels than those without metastasis. Both transwell and wound-healing assays indicated that Fn infection promoted the migration and invasion of GC cells. Western blot analysis showed that Fn infection decreased the expression of E-cadherin and increased the expressions of N-cadherin, vimentin, and snail. CONCLUSION: Fn abundance in saliva could be used as a promising biomarker to diagnose GC, and Fn infection could promote GC metastasis by accelerating the EMT process.
Subject(s)
Carcinoembryonic Antigen , Stomach Neoplasms , Adenomatous Polyps , Biomarkers, Tumor , CA-19-9 Antigen , Cadherins , Ferritins , Fusobacterium nucleatum , Humans , N-Acetylneuraminic Acid , Prognosis , Stomach Neoplasms/pathology , VimentinABSTRACT
To evaluate the health benefits brought about by air environmental treatment and determine the main drivers of health risk, we calculated the health and economic benefits attributed to PM2.5 control in Eastern and Central China from 2013 to 2017 by combining PM2.5 concentrations with a human activity enhanced exposure-response model. The relative contributions of changes in four factors related to the PM2.5 health burden were also quantified, namely total population, population aging, baseline mortality rates, and ambient exposure. The results show that the population weighted PM2.5 concentration decreased by 28.73% and the proportion of the population exposed to annual PM2.5 concentrations lower than or equal to 35 µg·m-3 increased from 11.23% to 27.91% across the study area during this period. Avoided deaths were decreased to 14.43%, which equates to avoided economic losses of approximately 559 billion RMB. If PM2.5 concentration meets the Chinese Ambient Air Quality Standard Grade â ¡ (35 µg·m-3) or Grade â (15 µg·m-3), or the World Health Organization Air Quality Guidelines (AQG) standards (10 µg·m-3), a 8.22%, 55.05%, and 79.36% reduction in the total deaths could be achieved in the base year (2017) with equivalent total economic benefits of approximately 319, 2137, and 3081 billion RMB, respectively. Total population, population aging, baseline mortality rates, and PM2.5 concentrations contributed -2.69%, -12.38%, 1.66%, and 14.57% to PM2.5-related deaths. Overall, during the study period, the reduction in PM2.5 concentrations has been the main factor contributing to the reduction in the public health burden. China has implemented significant air pollution control measures; however, the health burden associated with high PM2.5 concentrations in densely populated areas is still extremely high, requiring an aggressive air pollution control strategy.
Subject(s)
Air Pollutants , Air Pollution , Air Pollutants/analysis , Air Pollution/analysis , Air Pollution/prevention & control , China , Environmental Exposure , Humans , Particulate Matter/analysis , Public HealthABSTRACT
Nutrients in runoff degrade water quality. The development of schemes to mitigate such degradation requires a characterization of the underlying dynamic processes of nutrient loss. The drinking-water source protection area in the Lake Hongfeng watershed of Guiyang City, the capital of Guizhou Province, China, has been delimited for effective conservation. However, no systematic observations have provided data on nutrient losses from these areas that could support optimal management. We selected one typical watershed in the area. Automatic gauges were installed to record the water levels and calculate runoff rates during 2010 and 2011. A total of 1523 runoff samples were collected at an interval of 3 h during a day; total nitrogen (TN), total phosphorus (TP), and chemical oxygen demand (COD) were tested. The results indicated that surface runoff rates were primarily less than 15 L/s but rapidly increased 1-30 times 15 L/s when it rained. TN, TP, and COD concentrations primarily fluctuated between 0.06 and 18.79 mg/L, between 0.01 and 1.57 mg/L, and between 0.01 and 160 mg/L, respectively. TN and COD concentrations in 98.98% and 52.04% of the runoff samples, respectively, exceeded the upper limit required by the Environmental Quality Standards for Surface Water (EQSSW) in China. Conversely, 94.29% of the runoff samples had lower concentrations than the upper limit of TP concentration. Surface runoff has been seriously polluted by nitrogen and organic pollutants. The occurrence frequency of different runoff rates and TP and COD concentrations showed different distributions, but TN concentrations had a normal distribution. There was a significant relationship between runoff rates and TP concentration and TN, TP, or COD loss. TN, TP, and COD loss primarily occurred on vegetable lands, rice fields, and residential sites. Effectively controlling nitrogen fertilizer that is applied on vegetable lands and paddy fields and managing wastewater and solid waste are urgent. The results reported here will also provide references for many other regions facing similar problems.