A randomized, parallel controlled, open-label clinical trial was conducted to evaluate the effect of a botanic compound berberine (BBR) on NAFLD.
A randomized, parallel controlled, open-label ...clinical trial was conducted in three medical centers (NIH Registration number: NCT00633282). A total of 184 eligible patients with NAFLD were enrolled and randomly received (i) lifestyle intervention (LSI), (ii) LSI plus pioglitazone (PGZ) 15mg qd, and (iii) LSI plus BBR 0.5g tid, respectively, for 16 weeks. Hepatic fat content (HFC), serum glucose and lipid profiles, liver enzymes and serum and urine BBR concentrations were assessed before and after treatment. We also analyzed hepatic BBR content and expression of genes related to glucose and lipid metabolism in an animal model of NAFLD treated with BBR.
As compared with LSI, BBR treatment plus LSI resulted in a significant reduction of HFC (52.7% vs 36.4%, p = 0.008), paralleled with better improvement in body weight, HOMA-IR, and serum lipid profiles (all p<0.05). BBR was more effective than PGZ 15mg qd in reducing body weight and improving lipid profile. BBR-related adverse events were mild and mainly occurred in digestive system. Serum and urine BBR concentrations were 6.99ng/ml and 79.2ng/ml, respectively, in the BBR-treated subjects. Animal experiments showed that BBR located favorably in the liver and altered hepatic metabolism-related gene expression.
BBR ameliorates NAFLD and related metabolic disorders. The therapeutic effect of BBR on NAFLD may involve a direct regulation of hepatic lipid metabolism.
ClinicalTrials.gov NCT00633282.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Alcohol metabolism causes hepatocytes to release damage‐associated molecular patterns (DAMPs). This includes mitochondrial DNA (mtDNA), which is generated and released from damaged hepatocytes and ...contributes to liver injury by producing proinflammatory cytokines. STING is a pattern recognition receptor of DAMPs known to control the induction of innate immunity in various pathological processes. However, the expression profile and functions of STING in the Gao binge ethanol model remain poorly understood. We demonstrated that STING is upregulated in the Gao binge ethanol model. STING functions as an mtDNA sensor in the Kupffer cells of the liver and induces STING‐signaling pathway‐dependent inflammation and further aggravates hepatocyte apoptosis in the Gao binge ethanol model. This study provides novel insights into predicting disease progression and developing targeted therapies for alcoholic liver injury.
Targeting of Stimulator of IFN genes (STING, also referred to as Tmem173) is a potential strategy for alcoholic liver injury. Mechanistically, STING functions as an mitochondrial DNA (mtDNA) sensor in the Kupffer cells (KCs) and induces cGAS‐STING dependent inflammation and hepatocyte apoptosis in the model of Gao binge ethanol feeding.
Global warming has obtained more and more attention because the global mean surface temperature has increased since the late 19th century. As more than 50% of the human population lives in cities, ...urbanization has become an important contributor for global warming. Pearl River Delta (PRD) in Guangdong Province, southern China, is one of the regions experiencing rapid urbanization that has resulted in remarkable Urban Heat Island (UHI) effect, which will be sure to influence the regional climate, environment, and socio-economic development. In this study, Landsat TM and ETM+ images from 1990 to 2000 in the PRD were selected to retrieve the brightness temperatures and land use/cover types. A new index, Normalized Difference Bareness Index (NDBaI), was proposed to extract bare land from the satellite images. Additionally, Shenzhen, which has experienced the fastest urbanization in Guangdong Province, was taken as an example to analyze the temperature distribution and changes within a large city as its size expanded in the past decade. Results show that the UHI effect has become more prominent in areas of rapid urbanization in the PRD region. The spatial distribution of heat islands has been changed from a mixed pattern, where bare land, semi-bare land and land under development were warmer than other surface types, to extensive UHI. Our analysis showed that higher temperature in the UHI was located with a scattered pattern, which was related to certain land-cover types. In order to analyze the relationship between UHI and land-cover changes, this study attempted to employ a quantitative approach in exploring the relationship between temperature and several indices, including the Normalized Difference Vegetation Index (NDVI), Normalized Difference Water Index (NDWI), Normalized Difference Bareness Index (NDBaI) and Normalized Difference Build-up Index (NDBI). It was found that correlations between NDVI, NDWI, NDBaI and temperature are negative when NDVI is limited in range, but positive correlation is shown between NDBI and temperature.
The aim of this study was to compare the therapeutic value and treatment-related complications of radical hysterectomy with those of concurrent chemoradiotherapy (CCRT) for locally resectable ...(T1a2-T2a1) stage IIIC1r cervical cancer.
A total of 213 patients with locally resectable stage IIIC1r cervical cancer who had been treated at Jiangxi Maternal and Child Health Care Hospital between January 2013 and December 2021 were included in the study and classified into two groups: surgery (148 patients) and CCRT (65 patients). The disease-free survival (DFS) rate, overall survival (OS) rate, side effects, and economic costs associated with the two groups were compared.
43.9% (65/148) patients in the surgical group had no pelvic lymph node metastasis, and 21of them did not require supplementary treatment after surgery due to a low risk of postoperative pathology. The median follow-up time was 46 months (range: 7-108 months). The five-year DFS and OS rates of the surgery group were slightly higher than those of the CCRT group (80.7% vs. 75.1% and 81.6% vs. 80.6%, respectively; p > 0.05). The incidences of grade III-IV gastrointestinal reactions in the surgery and CCRT groups were 5.5% and 9.2%, respectively (p = 0.332). Grade III-IV myelosuppression was identified in 27.6% of the surgery group and 26.2% of the CCRT group (p = 0.836). The per capita treatment cost was higher for the surgery group than for the CCRT group (RMB 123, 918.6 0 vs. RMB 101, 880.90, p = 0.001).
The therapeutic effects and treatment-related complications of hysterectomy and CCRT are equivalent in patients with locally resectable stage IIIC1r cervical cancer, but surgery can provide accurate lymph node information and benefit patients with unnecessary radiation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide. Macrophages exhibit different functional states and are classified as classically activated (M1) and alternatively ...activated (M2) macrophages. However, the mechanisms that govern M1/M2 polarization in chronic ALD remain to be elucidated. Prostacyclin (PGI2) synthase (PTGIS) is an enzyme of the prostaglandin pathway which catalyzes the conversion of Prostaglandin H2 (PGH2) to PGI2. PTGIS has anti-inflammatory properties. However, the function of PTGIS in ALD has not yet been determined. In this study, we demonstrated that PTGIS was downregulated in ALD and forced PTGIS expression in vivo using recombinant adeno-associated viral vector-packed PTGIS overexpression plasmid, which alleviated the inflammatory response and suppressed the macrophage M1 phenotype in mice. Loss- and gain-of function-experiments demonstrated that forced PTGIS expression inhibited the macrophage switch to the M1 phenotype and promoted M2 polarization. Furthermore, we identified the genes regulated by PTGIS through RNA-sequencing (RNA-seq) analysis. Gene ontology and KEGG pathway analyses showed that PTGIS regulates many genes involved in the immune response and is enriched in the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signal transduction pathway, which plays an important role in regulating macrophage polarization. The proteins interacting with JAKs were predicted using the STRING database. The overlap between the RNA-seq and the STRING database was interleukin-6; this indicated that it was involved in macrophage polarization regulated by JAK/STAT signaling. We further explored the microRNAs that could regulate the expression of PTGIS through TargetScan. The results of luciferase assay illustrated that the expression of PTGIS was regulated by miR-140-3p.1. These results imply that PTGIS plays a pivotal role in ALD, partly by influencing macrophage polarization.
Prostacyclin synthase (PTGIS) levels are decreased by elevated miR-140-3p.1 expression in chronic alcoholic liver disease. Inducing PTGIS expression alleviates chronic alcohol-induced liver injury by promoting macrophage M2 polarization and inhibiting the M1 phenotype through the JAK/STAT pathway. Interestingly, inducing PTGIS expression also increases IL-6 expression, which has not yet been explained.
Background
Metabolic abnormalities in patients with gastric adenocarcinoma lead to drug resistance and poor prognosis. Therefore, this study aimed to explore biomarkers that can predict the ...prognostic risk of gastric adenocarcinoma by analyzing drug metabolism‐related genes.
Methods
The RNA‐seq and clinical information on gastric adenocarcinoma were downloaded from the UCSC and gene expression omnibus databases. Univariate and least absolute shrinkage and selection operator regression analyses were used to identify the prognostic gene signature of gastric adenocarcinoma. The relationships between gastric adenocarcinoma prognostic risk and tumor microenvironment were assessed using CIBERSORT, EPIC, QUANTISEQ, MCPCounter, xCell, and TIMER algorithms. The potential drugs that could target the gene signatures were predicted in WebGestalt, and molecular docking analysis verified their binding stabilities.
Results
Combined with clinical information, an eight‐gene signature, including GPX3, ABCA1, NNMT, NOS3, SLCO4A1, ADH4, DHRS7, and TAP1, was identified from the drug metabolism‐related gene set. Based on their expressions, risk scores were calculated, and patients were divided into high‐ and low‐risk groups, which had significant differences in survival status and immune infiltrations. Risk group was also identified as an independent prognostic factor of gastric adenocarcinoma, and the established prognostic and nomogram models exhibited excellent capacities for predicting prognosis. Finally, miconazole and niacin were predicted as potential therapeutic drugs for gastric adenocarcinoma that bond stably with NOS3 and NNMT through hydrogen interactions.
Conclusions
This study proposed a drug metabolism‐related eight‐gene signature as a potential biomarker to predict the gastric adenocarcinoma prognosis risks.
Objective: Metabolic abnormalities in patients with gastric adenocarcinoma (GA) lead to the development of drug resistance and a poor prognosis. Therefore, this study aims to explore biomarkers that can predict the prognostic risk of GA from the perspective of drug metabolism. Methods: RNA‐seq and clinical information of GA were downloaded from UCSC and GEO. The univariate and LASSO regression analyses were used to identify prognostic gene signatures of GA. The relationships between GA prognostic risk and tumor microenvironment were assessed by CIBERSORT, EPIC, QUANTISEQ, MCPCounter, Xcell and TIMER algorithms. The potential drugs of feature genes were predicted in Webgestal and molecular docking analysis was generated to verify their binding stabilities. Results: Combined with clinical information, 8 gene signatures including GPX3, ABCA1, NNMT, NOS3, SLCO4A1, ADH4, DHRS7 and TAP1 were identified from drug‐metabolism‐related gene‐set. Based on their expressions, risk scores were calculated and patients were grouped into high‐risk and low‐risk. Survival analyses showed that patients in the high‐risk group had poorer outcomes. The risk group was also detected as an independent prognostic factor of GA, and the established prognostic and nomogram models both showed excellent capacities in predicting GA prognosis. Furthermore, we also revealed significant differences in immune cell infiltrations between risk groups. Finally, Miconazole and Niacin were predicted as potential therapeutic drugs of GA that bond stably with NOS3 and NNMT through hydrogen interactions. Conclusions: This study proposed 8 gene signatures related with drug metabolism as potential biomarkers to predict the prognostic risk of patients with GA.
The main purpose of this study was to reveal the nutritional value and antioxidant activity of 34 edible flowers that grew in Yunnan Province, China, through a comprehensive assessment of their ...nutritional composition and antioxidant indices. The results showed that sample A3 of Asteraceae flowers had the highest total flavonoid content, with a value of 8.53%, and the maximum contents of vitamin C and reducing sugars were from Rosaceae sample R1 and Gentianaceae sample G3, with values of 143.80 mg/100 g and 7.82%, respectively. Samples R2 and R3 of Rosaceae were the top two flowers in terms of comprehensive nutritional quality. In addition, the antioxidant capacity of Rosaceae samples was evidently better than that of three others, in which Sample R1 had the maximum values in hydroxyl radical (
OH) scavenging and superoxide anion radical (
O
) scavenging rates, and samples R2 and R3 showed a high total antioxidant capacity and 2,2-diphenyl-1-pyridylhydrazine (DPPH) scavenging rate, respectively. Taken together, there were significant differences in the nutrient contents and antioxidant properties of these 34 flowers, and the comprehensive quality of Rosaceae samples was generally better than the other three families. This study provides references for 34 edible flowers to be used as dietary supplements and important sources of natural antioxidants.
Objective
To evaluate the changes of uterine leiomyoma size during pregnancy and determine the factors influencing it.
Methods
A prospective study was conducted from June 2016 to June 2018. Women ...with pregnancies complicated by leiomyoma were recruited. Ultrasound examinations were conducted to measure the size of leiomyoma during 6–7, 11–14, 22–24, 28–34 weeks of pregnancy and before delivery. The clinical characteristics and delivery details of the pregnant women were collected. Changes in leiomyoma size during different gestation periods and the influencing factors were analyzed.
Results
Leiomyoma size commonly increased before 22–24 weeks of pregnancy and the fastest growth occurred before 11–14 weeks. From 22–24 weeks to the date of delivery, the size of leiomyoma remained unchanged. The initial size of the leiomyoma showed negative correlation with the changes in leiomyoma diameters during pregnancy. Pre‐pregnancy body mass index, fetus number, leiomyoma location, and parity were positively correlated with the size changes in leiomyoma from 22–24 to 28–34 weeks of pregnancy.
Conclusion
Before 22–24 weeks of pregnancy, the size of the leiomyoma was gestation‐dependent, which increases with gestational weeks. The fastest growth rate was before 11–14 weeks. The growth of leiomyoma is affected by multiple factors, and different factors can play different roles during different periods of the pregnancy.
Leiomyoma size increases with gestational age before 22–24 gestational weeks and is affected by multiple factors.
Drosophila suzukii
is native to East Asia and an invasive pest of fruit crops widely established in the Americas and Europe. The lack of effective indigenous parasitoids of
D. suzukii
in the invaded ...regions prompted surveys for co-evolved parasitoids in Yunnan Province, China, from 2013 to 2016. From banana-baited traps (2013–2015), 458 parasitoids of drosophilids were reared, comprised of Braconidae (49.56%), Figitidae (37.55%), Diapriidae (7.42%), and Pteromalidae (5.46%). Larval parasitoids included seven braconid species, all
Asobara
and primarily
Asobara mesocauda
, and five figitid species, primarily
Leptopilina japonica japonica
. Pupal parasitoids were the diapriid
Trichopria drosophilae
and the pteromalid
Pachycrepoideus vindemiae
. Collections from wild fruits (2016) provided more interesting results. From the puparia of drosophilids collected, comprised of
D. suzukii
and
Drosophila pulchrella
, emerged 1354 parasitoids. The larval parasitoids
Ganaspis brasiliensis
and
L. j. japonica
were the prevalent species, reaching a fairly high percentage parasitism of fly puparia collected from berries of
Rubus foliosus
(22.35%),
R. niveus
(18.81%),
Fragaria moupinensis
(19.75%), and
Sambucus adnata
(63.46%).
Ganaspis brasiliensis
was the dominant species and was collected only from
D. suzukii
and
D. pulchrella
-infested fruits and never from banana-baited traps. Molecular analysis showed two
G. brasiliensis
lineages, which are discussed with respect to previous Japanese collections. Quarantine tests showed that
G. brasiliensis
developed from
D. suzukii
and two closely related hosts (
Drosophila melanogaster
and
Drosophila simulans
) but did not develop from seven non-target drosophilid species. Our results suggest that
G. brasiliensis
is a promising classical biocontrol agent for release in invaded regions.
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