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Ferroptosis is closely associated with the development of disease in the body. However, there are few studies on ferroptosis-related genes (FRGs) in obesity. Therefore, key genes and signalling pathways related to ferroptosis in obesity were screened. Briefly, the RNA sequencing data of obesity and the non-obesity human samples and 259 FRGs were downloaded from GEO database and FerrDb database, respectively. The obesity-related module genes were firstly screened by weighted gene co-expression network analysis (WGCNA) and crossed with differentially expressed genes (DEGs) of obesity/normal samples and FRGs to obtain obesity-ferroptosis related (OFR) DEGs. Then, key genes were screened by PPI network. Next, the correlation of key genes and differential immune cells between obesity and normal samples were further explored by immune infiltration analysis. Finally, microRNA (miRNA)-messenger RNA (mRNA), transcription factor (TF)-mRNA networks and drug-gene interaction networks were constructed. As a result, 17 OFR DEGs were obtained, which mainly participated in processes such as lipid metabolism or adipocyte differentiation. The 4 key genes, STAT3, IL-6, PTGS2, and VEGFA, constituted the network. M2 macrophages, T cells CD8, mast cells activated, and T cells CD4 memory resting had significant differences between obesity and normal samples. Moreover, 51 miRNAs and 164 drugs were predicted for 4 key genes. All in all, this study has screened 4 FRGs, including IL-6, VEGFA, STAT3, and PTGS2, in obesity patients. [ABSTRACT FROM AUTHOR]

Rubus (Rosaceae), one of the most complicated angiosperm genera, contains about 863 species, and is notorious for its taxonomic difficulty. The most recent (1910–1914) global taxonomic treatment of the genus was conducted by Focke, who defined 12 subgenera. Phylogenetic results over the past 25 years suggest that Focke's subdivisions of Rubus are not monophyletic, and large‐scale taxonomic revisions are necessary. Our objective was to provide a comprehensive phylogenetic analysis of the genus based on an integrative evidence approach. Morphological characters, obtained from our own investigation of living plants and examination of herbarium specimens are combined with chloroplast genomic data. Our dataset comprised 196 accessions representing 145 Rubus species (including cultivars and hybrids) and all of Focke's subgenera, including 60 endemic Chinese species. Maximum likelihood analyses inferred phylogenetic relationships. Our analyses concur with previous molecular studies, but with modifications. Our data strongly support the reclassification of several subgenera within Rubus. Our molecular analyses agree with others that only R. subg. Anoplobatus forms a monophyletic group. Other subgenera are para‐ or polyphyletic. We suggest a revised subgeneric framework to accommodate monophyletic groups. Character evolution is reconstructed, and diagnostic morphological characters for different clades are identified and discussed. Based on morphological and molecular evidence, we propose a new classification system with 10 subgenera: R. subg. Anoplobatus, R. subg. Batothamnus, R. subg. Chamaerubus, R. subg. Cylactis, R. subg. Dalibarda, R. subg. Idaeobatus, R. subg. Lineati, R. subg. Malachobatus, R. subg. Melanobatus, and R. subg. Rubus. The revised infrageneric nomenclature inferred from our analyses is provided along with synonymy and type citations. Our new taxonomic backbone is the first systematic and complete global revision of Rubus since Focke's treatment. It offers new insights into deep phylogenetic relationships of Rubus and has important theoretical and practical significance for the development and utilization of these important agronomic crops. [ABSTRACT FROM AUTHOR]

Background: Several studies have been performed to assess the relationship between hyperhomocysteinemia and type 2 diabetes mellitus (T2DM). However, inconsistent results have been obtained. Therefore, we performed this meta-analysis to address this knowledge gap. Methods: We searched PubMed, Cochrane library, and EMBASE database for studies that evaluated the relationship between blood homocysteine (HCY) level and T2DM from inception to Jun 2019. The quality of all included studies was assessed by the Newcastle Ottawa Scale (NOS) and the Agency for Healthcare Research Quality (AHRQ). RevMan5.3 and Stata12.0 were used for data analyses. Results: Twenty-five studies (including 1881 cases and 2868 controls) on blood HCY level in T2DM were pooled in our meta-analysis. The blood HCY level in the T2DM patients was significantly higher than in the healthy individuals (SMD = 0.63, 95% CI = 0.43–0.84, and p < 0.001, I2 = 89%, p < 0.001), ignores the effects of age, sex, cardiovascular and cerebrovascular disease conditions, and other comorbidity. Additionally, in T2DM patients with nephropathy or retinopathy, blood HCY level was also significantly higher than in those with only T2DM (SMD = 1.17, 95% CI = 0.76–1.58, p < 0.001; I2 = 90%, p < 0.001 and SMD = 0.91, 95% CI = 0.39–1.44, p <0.001; I2 = 82%, p <0.001, respectively). Conclusion: Our meta-analysis revealed the HCY level in the blood of T2DM patients was significantly higher than those of the health subjects, especially in patients with diabetic nephropathy (DN) and diabetic retinopathy (DR). [ABSTRACT FROM AUTHOR]

Pathogens commonly disrupt the intestinal epithelial barrier; however, how the epithelial immune system senses the loss of intestinal barrier as a danger signal to activate self-defense is unclear. Through an unbiased approach in the model nematode Caenorhabditis elegans, we found that the EGL-44/TEAD transcription factor and its transcriptional activator YAP-1/YAP (Yes-associated protein) were activated when the intestinal barrier was disrupted by infections with the pathogenic bacterium Pseudomonas aeruginosa PA14. Gene Ontology enrichment analysis of the genes containing the TEAD-binding sites revealed that "innate immune response" and "defense response to Gram-negative bacterium" were two top significantly overrepresented terms. Genetic inactivation of yap-1 and egl-44 significantly reduced the survival rate and promoted bacterial accumulation in worms after bacterial infections. Furthermore, we found that disturbance of the E-cadherin-based adherens junction triggered the nuclear translocation and activation of YAP-1/YAP in the gut of worms. Although YAP is a major downstream effector of the Hippo signaling, our study revealed that the activation of YAP-1/YAP was independent of the Hippo pathway during disruption of intestinal barrier. After screening 10 serine/threonine phosphatases, we identified that PP2A phosphatase was involved in the activation of YAP-1/YAP after intestinal barrier loss induced by bacterial infections. Additionally, our study demonstrated that the function of YAP was evolutionarily conserved in mice. Our study highlights how the intestinal epithelium recognizes the loss of the epithelial barrier as a danger signal to deploy defenses against pathogens, uncovering an immune surveillance program in the intestinal epithelium. Author summary: The intestinal epithelial barrier is an important line of defense against pathogenic bacteria infecting the intestine. Persistent bacterial infections can cause disruption of the intestinal barrier; however, how the epithelia immune system recognizes the loss of intestinal barrier as a danger signal to activate self-defense against pathogens is unclear. Using the nematode Caenorhabditis elegans as a model animal, we show that the EGL-44/TEAD transcription factor and its transcriptional activator YAP-1/YAP (Yes-associated protein) are activated when the intestinal barrier is disrupted by bacterial infections. Gene Ontology enrichment reveals that EGL-44/TEAD orchestrates a complex host response composed of innate immune response and defense response to Gram-negative bacteria. Furthermore, our data demonstrate that YAP-1/YAP and EGL-44/TEAD are required for resistance to infections with pathogenic bacteria when the intestinal barrier is disrupted in worms and mice. Our study reveals a novel strategy for the intestinal epithelium to sense danger through its internal architecture and initiate innate immunity. [ABSTRACT FROM AUTHOR]

Background & Aims: Insulin resistance is strongly associated with non‐alcoholic fatty liver disease, a chronic, obesity–related liver disease. Increased endoplasmic reticulum (ER) stress plays an important role in the development of insulin resistance. In this study, we investigated the roles of miRNAs in regulating ER stress in the liver of rats with obesity. Methods: We used miRNA microarray to determine the miRNA expression profiles in the liver of rats fed with a high fat diet (HFD). We used prediction algorithms and luciferase reporter assay to identify the target gene of miRNAs. To overexpress the miRNA miR‐30b or inhibit miR‐30b rats were injected with lentivirus particles containing PGLV3‐miR‐30b or PGLV3‐miR‐30b antimiR through tail vein. Hepatic steatosis was measured using transient elastography in human subjects. Results: Our data showed that miR‐30b was markedly up‐regulated in the liver of HFD–treated rats. Bioinformatic and in vitro and in vivo studies led us to identify sarco(endo)plasmic reticulum Ca2+‐ATPase 2b (SERCA2b), as a novel target of miR‐30b. Overexpression of miR‐30b induced ER stress and insulin resistance in rats fed with normal diet, whereas inhibition of miR‐30b by miR‐30b antimiR suppressed ER stress and insulin resistance in HFD–treated rats. Finally, our data demonstrated that there was a positive correlation between serum miR‐30b levels and hepatic steatosis or homoeostasis model assessment of insulin resistance (HOMA‐IR) in human subjects. Conclusions: Our findings suggest that miR‐30b represents not only a potential target for the treatment of insulin resistance, but also a non‐invasive disease biomarker of NAFLD. [ABSTRACT FROM AUTHOR]

Raspberry ketone accounts for the characteristic aroma of the raspberry fruit. A bifunctional enzyme with both chalcone synthase (CHS) and benzalacetone synthase (BAS) activity is thought to play a crucial role in the synthesis of p-hydroxybenzalacetone, yet the in vitro enzymatic properties and reaction products of the CHS/BAS recombinant enzyme from raspberry have not been characterized. In this work, a type III polyketide synthase (PKS) gene ( RinPKS1) and its corresponding cDNA were isolated from raspberry. Sequence and phylogenetic analyses demonstrated that RinPKS1 is a CHS. However, functional and enzymatic analyses showed that recombinant RinPKS1 is a bifunctional enzyme with both CHS and BAS activity. RinPKS1 showed some interesting characteristics: (1) no traces of bis-noryangonin and 4-coumaroyltriacetic acid lactone could be detected in the enzyme reaction mixture at different pH values; and (2) recombinant RinPKS1 overexpressed in Escherichia coli effectively yielded p-hydroxybenzalacetone as a dominant product at high pH; however, it effectively yielded naringenin as a dominant product at low pH. Furthermore, 4-coumaroyl-CoA and feruloyl-CoA were the only cinnamoyl-CoA derivatives accepted as starter substrates. RinPKS1 did not accept isobutyryl-CoA, isovaleryl-CoA or acetyl-CoA as substrates. [ABSTRACT FROM AUTHOR]

Purpose: Since observational data in the urban residents are required to better assess the risk factors of colorectal neoplasm occurrence and the effectiveness of colonoscopy screening and surveillance, we conducted a case-control study at multicenters in China to identify patient characteristics and neoplasm features of colorectal adenoma (CRA) and colorectal carcinoma (CRC). Methods: A total of 4089 patients who had undergone a colonoscopy from 19 hospitals were enrolled, of which 1106 had CRA and 466 had CRC. They were compared with controls. The analysis provides features and risk factors of colorectal neoplasm using multivariate logistic regression. Results: Increasing age, a family history of colorectal cancer or previous cases of colorectal adenoma or hypertension disease, gastrointestinal surgery, regular intake of pickled food (adjusted odds ratio [aOR] 1.42, 95 % confidence interval [CI], 1.048-1.924), consumption of alcohol, and a positive result of fecal occult blood testing (FOBT; aOR 2.509, 95 % CI 1.485-4.237) were associated with an increased risk of CRA. In the CRC group, increasing age, regular intake of pickled foods, and a positive FOBT result were risk factors. In addition, a positive abdominal computed tomography (CT) before a colonoscopy and physical signs of emaciation were also significantly associated with an increasing risk of colorectal carcinoma. Regular intake of vegetables decreased the risk of both CRA and CRC. Conclusions: Age, pickled foods, and a positive FOBT are risk factors for colorectal neoplasm. Vegetable intake was associated with a decreased risk of CRA and CRC. [ABSTRACT FROM AUTHOR]

By using the TAIL-PCR and over-hang extension PCR methods, we successfully isolated a three-intron type III PKS gene and cDNA clone from the Polygonum cuspidatum Sieb. et Zucc, and named it PcPKS4. The phylogenetic analysis showed that PcPKS4 is located in a cluster containing all functionally divergent CHS-like enzymes from angiosperms. Interestingly, the CHS 'gatekeeper' phenylalanine, Phe265 is uniquely replaced by Leu in PcPKS4. Different from our previously results, RNA gel-blot analysis revealed that the PcPKS4 transcripts were present at a low level in roots. [ABSTRACT FROM AUTHOR]

In our recent work (Ma et al., in Planta 229(3):457-469, and 229(4):1077-1086, ), two three-intron type III PKS genes, PcPKS1 and PcPKS2, were isolated from Polygonum cuspidatum Sieb. et Zucc. Phylogenetic and functional analyses revealed PcPKS1 is a three-intron chalcone synthase (CHS) gene, and PcPKS2 is found to be a three-intron benzalacetone synthase (BAS) gene. The regular CHS encoded by a single intron gene have not been isolated and characterized from P. cuspidatum. In this work a further CHS with one intron ( PcPKS3) and a stilbene synthase (STS) gene with three-intron ( PcPKS5) were isolated and characterized by functional and phylogenetic analyses. In comparison with PcPKS1, a bifunctional enzyme with both CHS and BAS activity, the enzymatic product of recombinant PcPKS3 was naringenin, bis-noryangonin (BNY) and 4-coumaroyltriacetic acid lactone (CTAL) occurred as side products. The PcPKS5 synthesized resveratrol and a trace amount of naringenin from p-coumaroyl-CoA. To our knowledge, PcPKS5 is the first reported three-intron STS gene in flowering plants. In this work, we speculated that this involved a possible evolutionary route of plant-specific type III PKS superfamily in P. cuspidatum. [ABSTRACT FROM AUTHOR]

Salidroside, the 8- O-β- d-glucoside of tyrosol, is the main bioactive component of Rhodiola species and is found mainly in the plant roots. It is well known that glucosylation of tyrosol is the final step in the biosynthesis of salidroside; however, the biosynthetic pathway of tyrosol and its regulation are less well understood. A summary of the results of related studies revealed that the precursor of tyrosol might be tyramine, which is synthesized from tyrosine. In this study, a cDNA clone encoding tyrosine decarboxylase (TyrDC) was isolated from Rhodiola sachalinensis A. Bor using rapid amplification of cDNA ends. The resulting cDNA was designated RsTyrDC. RNA gel-blot analysis revealed that the predominant sites of expression in plants are the roots and high levels of transcripts are also found in callus tissue culture. Functional analysis revealed that tyrosine was best substrate of recombinant RsTyrDC. The over-expression of the sense- RsTyrDC resulted in a marked increase of tyrosol and salidroside content, but the levels of tyrosol and salidroside were 274 and 412%, respectively, lower in the antisense- RsTyrDC transformed lines than those in the controls. The data presented here provide in vitro and in vivo evidence that the RsTyrDC can regulate the tyrosol and salidroside biosynthesis, and the RsTyrDC is most likely to have an important function in the initial reaction of the salidroside biosynthesis pathway in R. sachalinensis. [ABSTRACT FROM AUTHOR]

A vacuolar Na+/H+ antiporter cDNA gene was successfully isolated fromHordeum brevisubulatum(Trin.) Link using the rapid amplification of cDNA ends (RACE) method. The gene was namedHbNHX1and was found to consist of 1 916 bp encoding a predicted polypeptide of 540 amino acids with a conserved amiloride-binding domain. Phylogenetic tree analysis of the Na+/H+ antiporters showed that theHbNHX1gene shares 55.3%–74.8% similarity with the vacuolar-type Na+/H+ antiporters. Transgenic tobaccos that contain theHbNHX1gene, integrated by forward insertion into the tobacco genome, were obtained viaAgrobacterium tumerfaciensand characterized for the determination of the concentration of Na+ and K+ ions, as well as proline, in the presence of 300 mmol/L NaCl. The T1 transgenic plants showed more tolerance to salt and drought than did wild-type plants. Our data suggest that overexpression of theHbNHX1gene could improve the tolerance of transgenic tobaccos to salt and drought through the function of the vacuolar Na+/H+ antiporter.(Managing editor: Li-Hui ZHAO) [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease, which has no standard treatment available. Panax notoginseng saponines (PNS) have recently been reported to protect liver against hepatocyte injury induced by ethanol or high fat diet (HFD) in rats. Compound K and ginsenoside Rh1 are the main metabolites of PNS. In this study, we evaluated the effects of CK and Rh1 on NAFLD. Rats fed HFD showed significant elevations in liver function markers, lipids, glucose tolerance, and insulin resistance. Treatment with CK or Rh1 either alone or in combination dramatically ameliorated the liver function impairment induced by HFD. Histologically, CK and Rh1 significantly reversed HFD-induced hepatocyte injury and liver fibrosis. In vitro experiments demonstrated that treatment with CK or Rh1 alone or in combination markedly induced cell apoptosis, and inhibited cell proliferation and activation in HSC-T6 cells. Additionally, CK and Rh1, either alone or in combination, also repressed the expression of fibrotic factors TIMP-1, PC-I, and PC-III. Taken together, our results demonstrate that CK and Rh1 have positive effects on NAFLD via the anti-fibrotic and hepatoprotective activity. [ABSTRACT FROM AUTHOR]