Obesity develops when energy intake exceeds energy expenditure. Promoting brown adipose tissue formation and function increases energy expenditure and hence may counteract obesity. Berberine (BBR) is ...a compound derived from the Chinese medicinal plant Coptis chinensis. Here we show that BBR increases energy expenditure, limits weight gain, improves cold tolerance and enhances brown adipose tissue (BAT) activity in obese db/db mice. BBR markedly induces the development of brown-like adipocytes in inguinal, but not epididymal adipose depots. BBR also increases expression of UCP1 and other thermogenic genes in white and BAT and primary adipocytes via a mechanism involving AMPK and PGC-1α. BBR treatment also inhibits AMPK activity in the hypothalamus, but genetic activation of AMPK in the ventromedial nucleus of the hypothalamus does not prevent BBR-induced weight loss and activation of the thermogenic programme. Our findings establish a role for BBR in regulating organismal energy balance, which may have potential therapeutic implications for the treatment of obesity.
Abstract N6-methyladenosine (m6A) is the most abundant RNA modification of mammalian mRNAs and plays a vital role in many diseases, especially tumours. In recent years, m6A has become the topic of ...intense discussion in epigenetics. M6A modification is dynamically regulated by methyltransferases, demethylases and RNA-binding proteins. Ovarian cancer (OC) is a common but highly fatal malignancy in female. Increasing evidence shows that changes in m6A levels and the dysregulation of m6A regulators are associated with the occurrence, development or prognosis of OC. In this review, the latest studies on m6A and its regulators in OC have been summarized, and we focus on the key role of m6A modification in the development and progression of OC. Additionally, we also discuss the potential use of m6A modification and its regulators in the diagnosis and treatment of OC.
Lipid deposition in non-adipose tissue is associated with a propensity to obesity. Skeletal muscle mitochondrial dysfunction, evidenced by incomplete beta oxidation may contribute to ectopic lipid ...deposition during high fat diet-induced obesity. Berberine (BBR) has been proved to possess the properties of improving metabolic disorders in patients with obesity or type 2 diabetes mellitus. However, the precise mechanism remains obscure.
Mice were treated with berberine and metabolic profile were analyzed. Mitochondrial number and function were detected after berberine treatment in vitro and in vivo. The role of Adenosine 5‘-monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) was verified after RNA interference or adenovirus infection.
In the current study, we investigated the influence of berberine on the lipid deposition of skeletal muscle and found that berberine could increase the mitochondrial number and function both in vivo and in vitro. Furthermore, berberine promoted the expression of PGC-1α, the crucial transcriptional coactivator related to mitochondrial biogenesis and function, through AMPK pathway. Berberine reduced the basal oxygen consumption rates (OCR) but increased the maximal OCR in C2C12 myocytes, which indicated that berberine could increase the potential function of mitochondria.
Our results proved that berberine can protect the lean body mass from excessive lipid accumulation, by promoting the mitochondrial biogenesis and improving fatty acid oxidation in an AMPK/PGC-1α dependent manner.
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•Berberine could prevent the lipid deposition in skeletal muscle.•Berberine could improve the hyperglycemia, hyperlipidemia and restrain the body weight gain in obese mice.•The mitochondrial content, function and fatty acid oxidation were all proved by berberine in skeletal muscle.•These beneficial effects of berberine were AMPK/PGC-1α pathway dependent.
Perivascular epithelioid cell neoplasms (PEComas) are a family of mesenchymal tumors with features of both smooth muscle and melanocytic differentiation. A subset of PEComas demonstrate ...rearrangements involving the TFE3 (Xp11) locus. Xp11 translocation PEComa is a rare neoplasm with special clinicopathological features and a more aggressive behavior. We recently encountered a case of Xp11 translocation PEComa occurring in the testis, with SFPQ⁃TFE3 rearrangement.
A 57-year-old male touched a mass in his testis incidentally. MRI revealed a 10 mm diameter mass in the right testis. The patient underwent radical orchiectomy. Gross examination revealed a well-demarcated mass from the surrounding testicular tissue. Microscopically, the tumor mainly displayed nested or sheet-like architecture separated by delicate fibrovascular septa. The tumor cells exhibited marked nuclear atypia and pleomorphism. Immunohistochemistry showed that the tumor cells were strongly positive for cathepsin-K, HMB45 and TFE3. Molecular analysis revealed SFPQ⁃TFE3 gene fusion. Thus, it was diagnosed as primary Xp11 translocation PEComa of the testis.
The present case reports primary Xp11 translocation PEComa of the testis for the first time, which to our knowledge has not been described in the literature in this anatomic site, where it could potentially be problematic in diagnosis.
The histological spectrum of nonalcoholic fatty liver diseases (NAFLD) ranges from hepatic steatosis to steatohepatitis and fibrosis. Berberine (BBR) is known for its therapeutic effect on obesity, ...hyperglycaemia and dyslipidaemia; however, its effect on NAFLD has yet to be thoroughly explored. Db/db mice and methionine-choline-deficient diet-fed mice were administered BBR via gavage. We found that BBR-treated mice were more resistant to steatosis in the liver than vehicle-treated mice and that BBR significantly reduced hepatic inflammation, fibrosis and lipid peroxides. The beneficial effect of BBR was associated with suppressing endoplasmic reticulum (ER) stress. Additionally, BBR decreased the free fatty acid-induced lipid accumulation and tunicamycin-induced ER stress in primary hepatocytes and hepatocyte cell lines. We demonstrated that BBR exhibited chaperone activity, reduced protein aggregation in vitro and alleviated tunicamycin-induced triglyceride and collagen deposition in vivo. Finally, we showed that BBR could reverse ER stress-activated lipogenesis through the ATF6/SREBP-1c pathway in vitro. These results indicated that BBR may be a new therapeutic strategy against hepatic steatosis and non-alcoholic steatohepatitis.
The phosphatases of regenerating liver (PRLs) are involved in tumorigenesis and metastatic cancer yet their cellular function remains unclear. Recent reports have shown PRL phosphatases bind tightly ...to the CNNM family of membrane proteins to regulate magnesium efflux. Here, we characterize the interactions between the CBS-pair (Bateman) domain of CNNM3 and either PRL2 or PRL3 using X-ray crystallography, isothermal titration calorimetry, and activity assays. We report four new crystal structures of PRL proteins bound to the CNNM3 CBS-pair domain that reveal the effects of cysteine disulphide formation and nucleotide binding on complex formation. We use comprehensive mutagenesis of the PRL3 catalytic site to quantify the importance of different PRL amino acids, including cysteine 104, leucine 108, and arginine 110, for CNNM binding and phosphatase activity. We show the PRL3 R138E mutant is selectively deficient in CNNM3 binding with the potential to distinguish between the downstream effects of phosphatase and CNNM-binding activities in vivo. Through a novel activity assay, we show that PRL3 has magnesium-sensitive phosphatase activity with ATP and other nucleotides. Our results identify a strong correlation between phosphatase activity and CNNM binding and support the contention that PRL function as pseudophosphatases regulated by chemical modifications of their catalytic cysteine.
The purpose of this propensity score matching (PSM) analysis was to compare the effects of preoperative transcatheter arterial chemoembolization (TACE) and non-TACE on the long-term survival of ...patients who undergo radical hepatectomy.
PSM analysis was performed for 387 patients with hepatocellular carcinoma (HCC) (single > 3 cm or multiple) who underwent radical resection of HCC at our centre from January 2011 to June 2018. The patients were allocated to a preoperative TACE group (n = 77) and a non-TACE group (n = 310). The main outcome measures were progression-free survival (PFS) and overall survival (OS) since the treatment date.
After PSM, 67 patients were included in each of the TACE and non-TACE groups. The median PFS times in the preoperative TACE and non-TACE groups were 24.0 and 11.3 months, respectively (p = 0.0117). The median OS times in the preoperative TACE and non-TACE groups were 41.5 and 29.0 months, respectively (p = 0.0114). Multivariate Cox proportional hazard regression analysis revealed that preoperative TACE (hazard ratio, 1.733; 95% CI, 1.168-2.570) and tumour thrombosis (hazard ratio, 0.323; 95% CI, 0.141-0.742) were independent risk factors significantly associated with OS.
Preoperative TACE is related to improving PFS and OS after resection of HCC. Preoperative TACE and tumour thrombus volume were also found to be independent risk factors associated with OS.
Long non-coding RNAs (lncRNAs) play crucial roles in ovarian cancer (OC) development. However, prognosis-associated lncRNAs (PALs) for OC have not been completely elucidated. Our study aimed to ...identify the PAL signature of OC. A total of 663 differentially expressed lncRNAs were identified in the databases. According to the weighted gene coexpression analysis, the highly correlated genes were clustered into seven modules related to the clinical phenotype of OC. A total of 25 lncRNAs that were significantly related to overall survival were screened based on univariate Cox regression analysis. The prognostic risk model constructed contained seven PALs based on the parameter λ
min
, which could stratify OC patients into two risk groups. The results showed that the risk groups had different overall survival rates in both The Cancer Genome Atlas (TCGA) and two verified Gene Expression Omnibus (GEO) databases. Univariate and multivariate Cox regression analyses confirmed that the risk model was an independent risk factor for OC. Gene enrichment analysis revealed that the identified genes were involved in some pathways of malignancy. The competitive endogenous RNA (ceRNA) network included five PALs, of which four were selected for cell function assays. The four PALs were downregulated in 33 collected OC tissues and 3 OC cell lines relative to the control. They were shown to regulate the proliferative, migratory, and invasive potential of OC cells via Cell Counting Kit-8 (CCK-8) and transwell assays. Our study fills the gaps of the four PALs in OC, which are worthy of further study.
Battery storage is one of the important units in the optimal scheduling of integrated energy systems. To give full play to the advantages of battery storage in stabilizing power quality and smoothing ...the output of intermittent new energy generation, the battery life decay problem needs to be considered in optimal scheduling. In this paper, we studied the energy storage life decay model and established an electric–gas integrated energy system model considering energy storage life decay to minimize the economic cost of system operations and to compare the optimal dispatch results with and without energy storage life decay through simulation analysis to verify the rationality and economy of the energy storage life decay model used in this paper.
In order to reveal the water-induced damage mechanism and mechanical properties of red-layers in Southern China, typical red-layer samples are experimentally studied by scanning electron microscope ...(SEM), energy spectrum analysis, XRD, and mechanical tests. The results show that some red-layer samples contain a large number of smectite and illite-smectite mixed-layer clay minerals and their microstructures are mainly stacked microaggregates in which mutual agglomeration is formed by flake and tabular clay particles. Widespread distribution micropores and fractures in microaggregates provide the necessary moisture migration channels. The various cemented materials produce a kind of irreversible structural strength, and this strength is vulnerable for the aqueous medium conditions. The influence of microstructures and mineral compositions on red-layer mechanical properties is discussed. The results could provide the reference for further research about the water-induced damage mechanism of red-layers in Southern China.
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