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AIMS/HYPOTHESIS: Mutations in Isl1, encoding the insulin enhancer-binding protein islet-1 (ISL1), may contribute to attenuated insulin secretion in type 2 diabetes mellitus. We made an Isl1E283D mouse model to investigate the disease-causing mechanism of diabetes mellitus. METHODS: The ISL1E283D mutation (c. 849A>T) was identified by whole exome sequencing on an early-onset type 2 diabetes family and then the Isl1E283D knockin (KI) mouse model was created and an IPGTT and IPITT were conducted. Glucose-stimulated insulin secretion (GSIS), expression of Ins2 and other ISL1 target genes and interacting proteins were evaluated in isolated pancreas islets. Transcriptional activity of Isl1E283D was evaluated by cell-based luciferase reporter assay and electrophoretic mobility shift assay, and the expression levels of Ins2 driven by Isl1 wild-type (Isl1WT) and Isl1E283D mutation in rat INS-1 cells were determined by RT-PCR and western blotting. RESULTS: Impaired GSIS and elevated glucose level were observed in Isl1E283D KI mice while expression of Ins2 and other ISL1 target genes Mafa, Pdx1, Slc2a2 and the interacting protein NeuroD1 were downregulated in isolated islets. Transcriptional activity of the Isl1E283D mutation for Ins2 was reduced by 59.3%, and resulted in a marked downregulation of Ins2 expression when it was overexpressed in INS-1 cells, while overexpression of Isl1WT led to an upregulation of Ins2 expression. CONCLUSIONS/INTERPRETATION: Isl1E283D mutation reduces insulin expression and secretion by regulating insulin and other target genes, as well as its interacting proteins such as NeuroD1, leading to the development of glucose intolerance in the KI mice, which recapitulated the human diabetic phenotype. This study identified and highlighted the Isl1E283D mutation as a novel causative factor for type 2 diabetes, and suggested that targeting transcription factor ISL1 could offer an innovative avenue for the precise treatment of human type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Proteínas com Homeodomínio LIM , Mutação de Sentido Incorreto , Fatores de Transcrição , Animais , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Proteínas com Homeodomínio LIM/genética , Proteínas com Homeodomínio LIM/metabolismo , Camundongos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Humanos , Masculino , Insulina/metabolismo , Feminino , Ratos , Secreção de Insulina/genética , Ilhotas Pancreáticas/metabolismoRESUMO
Bottle gourd [Lagenaria siceraria (Mol.) Stand] is a widely cultivated succulent crop species. In December 2022, a serious bottle gourd disease occurred in the protected vegetable planting base of Xingguo County, Ganzhou City, Jiangxi Province, China, with 85% of the 2,100 plants having gray mold disease-like symptoms, including gray spots on the infected fruit. They quickly expanded at suitable temperature and humidity, forming a gray mold layer with inward depressions, which spread to the fruit stem causing watery rot, and the flesh turned black and started to rot. To isolate the pathogen, fruits of the diseased plants were surface-disinfected with 75% ethanol for 30 s, immersed in 0.1% HgCl2 for 1 min, rinsed thrice with sterile water, and cultured on a potato-dextrose agar (PDA) medium at 28°C. Mycelia from the diseased tissue were subcultured on fresh PDA medium to obtain pure cultures. After incubation at 25°C for 7 days, olive-green colonies (~2.5 mm·d-1) developed. Cultures developed numerous elliptical and limoniform conidia measuring 2.69~9.79 µm to 2.10~5.92 µm (average 5.62×3.12 µm) (n=20). The morphological characteristics of the pathogen resembled those of Cladosporium spp. Fungal genomic DNA was extracted, and the internal transcribed spacer (ITS), partial translation elongation factor-1 alpha (TEF-1α), and actin (ACT) regions were amplified with primers ITS1/4, TEF-728F/986R, and ACT-512F/783R, respectively, and sequenced (Bensch et al. 2012; Jo et al. 2018). Basic Local Alignment Search Tool analysis (BLAST) revealed that the ITS (accession no. OQ186729), ACT (OQ240962), and TEF-1α (OQ240963) sequences of isolate hjt4 shared the highest similarity (99-100%) with those of Cladosporium tenuissimum (accessions no. OM232068, OM256530, OM256526) (Duccio et al. 2015). A phylogenetic tree of the isolate hjt4 and its close relatives within Cladosporium was constructed using the MEGA X neighbor-joining method. The pathogen was identified as C. tenuissimum based on morphological and molecular characteristics. A specimen (JXAU-H2022982) was deposited at the Herbarium of the College of Agronomy, Jiangxi Agricultural University. To confirm its pathogenicity, seven-day-old healthy bottle gourd fruits were disinfected with 75% ethanol, 1 mm-deep wounds were made with sterilized scalpels, and the plants were inoculated with PDA plugs (0.8 cm in diameter) containing actively growing mycelia of isolate hjt4. Plants inoculated with sterile PDA plugs served as controls. Each group contained three fruits, and the experiment was performed in triplicate. All fruits were incubated in a biochemical incubator at 28°C. After 3 days, the fruit surface shrank, and the flesh turned to a black colour and rotten, which rapidly spread to the branches. Control fruits did not develop any symptoms. Reisolated colonies showed the same morphological traits as those of the inoculation isolates, whereas no target colonies were isolated from the control fruits. The pathogen was previously reported to cause leaf blight disease in Coriandrum sativum (Zhou et al. 2022) and sooty spots on Cape gooseberry (Miyake et al. 2022), among others. To our knowledge, this is the first report of gray mold disease caused by C. tenuissimum on bottle gourd in China. The findings provide an important foundation for monitoring and controlling the spread of this disease.
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BACKGROUND: Metabolic syndrome (MetS), a worldwide public health problem, affects human health and quality of life in a dramatic manner. A growing evidence base suggests that MetS is strongly associated with levels of systemic immune inflammation. The present study aimed to investigate the possible relationship between the systemic immune-inflammation index (SII), a novel inflammatory marker, and MetS to provide data support for effective MetS prevention by reducing the systemic inflammatory response. METHODS: We included adult participants with complete SII and MetS information from the 2011-2016 National Health and Nutrition Examination Survey (NHANES). MetS was defined as using the criteria developed by the Adult Treatment Program III of the National Cholesterol Education Program. The formula for SII was as follows: SII = platelet counts × neutrophil counts/ lymphocyte counts. Weighted linear regression was used to assess differences in variables across SII quartile groups after the SII score was divided into 4 quartiles. The independent interaction between SII and MetS was investigated using weighted multivariate logistic regression analysis and subgroup analysis, and the relationship between SII levels and 5 particular MetS items was further explored in depth. RESULTS: A total of 12,402 participants, 3,489 of whom were diagnosed with MetS, were included in this study. After correcting for covariates, the results of a logistic regression of multistage weighted complex sampling data revealed that participants with higher SII scores had a higher chance of developing MetS (odds ratio (OR) = 1.33, 95% confidence interval (CI): 1.14-1.55) and that SII levels could be used as an independent risk factor to predict that likelihood of MetS onset. In the Q1-Q4 SII quartile group, the risk of developing MetS was 1.33 times higher in the Q4 group, which had the highest level of systemic immune inflammation than in the Q1 group. After adjusting for all confounding factors, SII scores were found to have a negative correlation with high-density lipoprotein cholesterol (OR = 1.29; 95% CI, 0.99-1.67, P = 0.056) and a significant positive correlation with waist circumference (OR = 2.17; 95% CI, 1.65-2.87, P < 0.001) and blood pressure (BP) (OR = 1.65; 95% CI, 1.20-2.27, P = 0.003). Gender, age, and smoking status were shown to alter the positive association between SII and MetS in subgroup analyses and interaction tests (p for interaction < 0.05). Additionally, we demonstrated a nonlinear correlation between SII and MetS. The findings of the restricted cubic spline indicated that there was an inverted U-shaped association between SII and MetS. CONCLUSIONS: Our findings imply that increased SII levels are related to MetS, and SII may be a simple and cost-effective method to identify individuals with MetS. Therefore, protective measures such as early investigation and anti-inflammatory interventions are necessary to reduce the overall incidence of MetS.
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Síndrome Metabólica , Adulto , Humanos , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Inquéritos Nutricionais , Qualidade de Vida , Inflamação/complicações , ColesterolRESUMO
Precise differentiation of glucokinase (GCK) monogenic diabetes from gestational diabetes mellitus (GDM) is critical for accurate management of the pregnancy outcome. We screened GCK-MODY complicating pregnancies in Chinese GDM patients, explored the pathogenesis of novel GCK mutations, and evaluated the patients' pregnancy outcome and management. The GCK gene from 411 GDM patients was screened with PCR-direct sequencing and multiplex ligation-dependent probe amplification (MLPA) and 15 GCK mutations were identified. We also retrospectively analyzed a total of 65 pregnancies from 21 GCK-MODY families, wherein 41 were from 15 maternal families and 24 were from six paternal families. Bioinformatic analysis and biochemical functional study were conducted to identify novel GCK mutations. In total, we identified 21 GCK mutations: 15 from the 411 GDM patients and six from 24 fathers. Of th Asp78Asn (GAC â AAC), Met87Arg (ATG â AGG), Leu451Val (CTT â GTT), Leu451Pro (CTG â CCG) and 1019 + 20G > A e mutations, five, i.e., were novel and deleterious, with markedly decreased enzyme activity and thermal stability. The unaffected offspring of GCK mutation-affected mothers were heavier than affected offspring (p < 0.001). Of 21 insulin-treated affected mothers, 10 had maternal hypoglycemia (47.6%) and seven had perinatal complications (33.3%), and the affected offspring of the insulin-treated affected mothers had significantly lower birth weights than that of the 20 diet-control affected mothers (p = 0.031). In this study, the prevalence of GCK-MODY complicating pregnancy in Chinese GDM patients was 3.6% (15/411). The defective GCK may contribute to the hyperglycemia in GCK-MODY. Insulin therapy is not beneficial for GCK-MODY complicating pregnancy and therefore should not be recommended.
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Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Gravidez em Diabéticas , China , Diabetes Mellitus Tipo 2/genética , Diabetes Gestacional/genética , Feminino , Glucoquinase/genética , Humanos , Insulina/genética , Mutação , Gravidez , Resultado da Gravidez , Gravidez em Diabéticas/epidemiologia , Gravidez em Diabéticas/genética , Gravidez em Diabéticas/terapia , Estudos RetrospectivosRESUMO
Rohdea japonica, known as Japanese sacred lily, a perennial herb in the family Asparagaceae, is an important ornamental plant in China (Hinkley 2006). In May 2022, at the campus of Jiangxi Agricultural University (28o45'50â³N, 115o50'2â³E), Nanchang, China, leaf spots occurred on R. japonica with a disease incidence of 95% (285/300 plants). Disease severity ranged from 40-60% of the leaf area on each plant. Symptoms initially appeared as small water-soaked spots, usually at the edges of the leaves. Then, the spots enlarged rapidly and became yellow brown, circular or semicircular. Finally, the dead tissues fell out of the leaf, leaving ragged leaf edges. Small pieces (3×3 mm) cut from the margin of necrotic leaf tissue were surface disinfested in 75% ethanol for 10 s and 0.1% HgCl2 for 20 s. After being rinsed three times with sterile distilled water, tissue was placed on potato dextrose agar (PDA) plates and incubated at 28â with a 12 h light-dark cycle. The growing fungal colonies were purified by subculturing hyphal tips, and 12 fungal isolates with similar morphology were obtained. Colonies were flat, smoke-grey with olivaceous green fan-shaped stripes. Conidia were single-celled, hyaline, slightly curved, both ends gradually tapering, measuring 14.9 - 25.3 µm long × 3.9 - 6.2 µm wide (n = 100). Appressoria were solitary, irregular, sometimes ellipsoidal, dark brown, measuring 6.5 - 17.6 µm long × 3.9 - 8.7 µm wide (n = 50). Morphological and cultural characteristics of the isolates matched the descriptions of Colletotrichum liriopes (Damm et al. 2009; Yang et al. 2020). To confirm the pathogens identity, genomic DNA of a representative isolate (WNQ1) was extracted, and the rDNA-ITS, TUB2 and CAL gene were amplified and sequenced using the primers ITS1/ITS4, T1/Bt2b, and CL1C/CL2C (White et al. 1990; Weir et al. 2012), respectively. The sequences were deposited in GenBank under accession number: ON514224 (rDNA-ITS), ON552548 (TUB2) and ON552549 (CAL). BLAST analyses showed 100%, 99.73% and 100% identity with 100% query coverage to the rDNA-ITS, TUB2 and CAL sequence of C. liriopes (MK644098, HM585414 and MN803417, respectively). Phylogenetic analysis using concatenated sequences of rDNA-ITS, TUB2 and CAL placed the isolate WNQ1 in a single clade with the reference strain of C. liriopes CORCK2. To confirm pathogenicity, a conidial suspension (1×106 conidia/ml) of isolate WNQ1 was sprayed on three leaves each of three healthy R. japonica plants wounded with a sterile needle, whereas control plants were wounded in the same way and sprayed with sterile distilled water. All treated plants were placed in a moist incubator at 28â with a 12 h photoperiod. Three days later symptoms, similar to those described above appeared. Symptoms did not develop on the control leaves. C. liriopes was recovered from the inoculated leaves, fulfilling Koch's postulates. Anthracnose caused by C. liriopes in R. japonica plants has been reported in the United States and Korea. To our knowledge, this is the first report of anthracnose on R. japonica caused by C. liriopes in China. The disease seriously affected the ornamental value of R. japonica. The result provides the foundation to study the occurrence patterns and control measures of R. japonica anthracnose.
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PIN2/TRF1-interacting telomerase inhibitor 1 (PinX1) can inhibit tumor growth by inhibiting telomerase activity. However, only few studies investigated the expression and function of PinX1 in nonalcoholic fatty liver disease (NAFLD). Thus, here we aimed to explore the roles of PinX1 in high-fat diet (HFD)-induced NAFLD in mice and in isolated hepatocytes. The mRNA expression of PinX1 and mTERT as well as telomere length were analyzed by RT-PCR. Pathological changes were detected by HE staining and oil red O staining. Triglyceride, cholesterol, alanine aminotransferase, aspartic aminotransferase, and telomerase activity were detected by ELISA. Hepatocyte apoptosis was determined by TUNEL and flow cytometry, and protein expression was analyzed by western blotting. We found that the expression of PinX1 was upregulated in the HFD group compared with the WT group. PinX1 knockout improved HFD-induced liver injury in mice and exhibited less lipid accumulation in hepatocytes. Moreover, telomere length, telomerase activity, and mTERT expression were significantly reduced in liver tissues of HFD-induced mice and palmitic acid-induced hepatocytes, while PinX1 knockout attenuated the effect. Furthermore, HFD-induced PinX1-/- mice exhibited less hepatocyte apoptosis than HFD-induced WT mice. Besides, PinX1 knockout inhibited the increase of cleaved caspase-3 and cleaved PARP expression in vivo and in vitro. Moreover, inhibition of mTERT reversed the effect of PinX1 knockout in hepatocytes. Taken together, our findings indicate that PinX1 promotes hepatocyte apoptosis and lipid accumulation by decreasing telomere length and telomerase activity in the development of NAFLD. PinX1 might be a target for the treatment of NAFLD.
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Apoptose , Proteínas de Ciclo Celular/deficiência , Fígado , Hepatopatia Gordurosa não Alcoólica/enzimologia , Hepatopatia Gordurosa não Alcoólica/patologia , Telomerase/metabolismo , Proteínas Supressoras de Tumor/deficiência , Animais , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Modelos Animais de Doenças , Hepatócitos/citologia , Hepatócitos/enzimologia , Hepatócitos/patologia , Fígado/citologia , Fígado/enzimologia , Fígado/patologia , Masculino , Camundongos , Hepatopatia Gordurosa não Alcoólica/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismoRESUMO
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Therapeutic activity of icariin, a major bioactive component of Epimedii Herba, in NAFLD is still unknown. Herein, the C57BL/6J mice were fed with a high-fat diet for 16 weeks to establish a NAFLD model. Mice were assigned to five groups: control group, NAFLD group, and icariin treatment groups. Effects of icariin on blood indices, glucose tolerance, insulin sensitivity, histopathological morphology, cell apoptosis, lipid accumulation, and AMPK signaling were analyzed. In addition, another cohort of mice were assigned to five groups: control group, NAFLD group, dorsomorphin treatment group, icariin treatment group, and dorsomorphin + icariin treatment group. Expression of proteins in liver tissues associated with AMPK signaling, and levels of ALT and AST were evaluated. Icariin attenuated the NAFLD-induced increase of the TG, TC, LDL-C, ALT, AST levels. HDL-C levels were affected neither by NAFLD nor by icariin. Furthermore, icariin treatment (100-200 mg/kg) counteracted the NAFLD-reduced glucose tolerance and insulin sensitivity and modulated histopathological changes, cell apoptosis, and lipid accumulation in liver tissues. Additionally, icariin mitigated the NAFLD-induced up-regulation of the cleaved caspase 3/9, SREBP-1c, and DGAT-2 levels, and enhanced the expression level of CPT-1, p-ACC/ACC, AMPKα1, PGC-1α, and GLUT4. Effects of icariin on the AMPK signaling and levels of AST and ALT could be reversed by AMPK inhibitor, dorsomorphin. This paper investigates the glucose-reducing and lipid-lowering effects of icariin in NAFLD. Moreover, icariin might function through activating the AMPKα1/PGC-1α/GLTU4 pathway.
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Proteínas Quinases Ativadas por AMP/metabolismo , Flavonoides/toxicidade , Transportador de Glucose Tipo 4/metabolismo , Hiperlipidemias , Fígado , Hepatopatia Gordurosa não Alcoólica , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Animais , Hiperlipidemias/induzido quimicamente , Hiperlipidemias/metabolismo , Hiperlipidemias/patologia , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genéticaRESUMO
BACKGROUND: Current approaches for the therapy of diabetic retinopathy (DR), which was one of leading causes of visual impairment, have their limitations. Animal experiments revealed that restructuring of intestinal microbiota can prevent retinopathy. AIM: To explore the relationship between intestinal microbiota and DR among patients in the southeast coast of China, and provide clues for novel ways to prevention and treatment methods of DR. METHODS: The fecal samples of non-diabetics (Group C, n = 15) and diabetics (Group DM, n = 30), including 15 samples with DR (Group DR) and 15 samples without DR (Group D), were analyzed by 16S rRNA sequencing. Intestinal microbiota compositions were compared between Group C and Group DM, Group DR and Group D, as well as patients with proliferative diabetic retinopathy (PDR) (Group PDR, n = 8) and patients without PDR (Group NPDR, n = 7). Spearman correlation analyses were performed to explore the associations between intestinal microbiota and clinical indicators. RESULTS: The alpha and beta diversity did not differ significantly between Group DR and Group D as well as Group PDR and Group NPDR. At the family level, Fusobacteriaceae, Desulfovibrionaceae and Pseudomonadaceae were significantly increased in Group DR than in Group D (P < 0.05, respectively). At the genera level, Fusobacterium, Pseudomonas, and Adlercreutzia were increased in Group DR than Group D while Senegalimassilia was decreased (P < 0.05, respectively). Pseudomonas was negatively correlated with NK cell count (r = -0.39, P = 0.03). Further, the abundance of genera Eubacterium (P < 0.01), Peptococcus, Desulfovibrio, Acetanaerobacterium and Negativibacillus (P < 0.05, respectively) were higher in Group PDR compared to Group NPDR, while Pseudomonas, Alloprevotella and Tyzzerella (P < 0.05, respectively) were lower. Acetanaerobacterium and Desulfovibrio were positively correlated with fasting insulin (r = 0.53 and 0.61, respectively, P < 0.05), when Negativibacillus was negatively correlated with B cell count (r = -0.67, P < 0.01). CONCLUSION: Our findings indicated that the alteration of gut microbiota was associated with DR and its severity among patients in the southeast coast of China, probably by multiple mechanisms such as producing short-chain fatty acids, influencing permeability of blood vessels, affecting levels of vascular cell adhesion molecule-1, hypoxia-inducible factor-1, B cell and insulin. Modulating gut microbiota composition might be a novel strategy for prevention of DR, particularly PDR in population above.
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Objective: To provide the current research progress, hotspots, and emerging trends for AI in liver cancer, we have compiled a relative comprehensive and quantitative report on the research of liver disease using artificial intelligence by employing bibliometrics in this study. Methods: In this study, the Web of Science Core Collection (WoSCC) database was used to perform systematic searches using keywords and a manual screening strategy, VOSviewer was used to analyze the degree of cooperation between countries/regions and institutions, as well as the co-occurrence of cooperation between authors and cited authors. Citespace was applied to generate a dual map to analyze the relationship of citing journals and citied journals and conduct a strong citation bursts ranking analysis of references. Online SRplot was used for in-depth keyword analysis and Microsoft Excel 2019 was used to collect the targeted variables from retrieved articles. Results: 1724 papers were collected in this study, including 1547 original articles and 177 reviews. The study of AI in liver cancer mostly began from 2003 and has developed rapidly from 2017. China has the largest number of publications, and the United States has the highest H-index and total citation counts. The top three most productive institutions are the League of European Research Universities, Sun Yat Sen University, and Zhejiang University. Jasjit S. Suri and Frontiers in Oncology are the most published author and journal, respectively. Keyword analysis showed that in addition to the research on liver cancer, research on liver cirrhosis, fatty liver disease, and liver fibrosis were also common. Computed tomography was the most used diagnostic tool, followed by ultrasound and magnetic resonance imaging. The diagnosis and differential diagnosis of liver cancer are currently the most widely adopted research goals, and comprehensive analyses of multi-type data and postoperative analysis of patients with advanced liver cancer are rare. The use of convolutional neural networks is the main technical method used in studies of AI on liver cancer. Conclusion: AI has undergone rapid development and has a wide application in the diagnosis and treatment of liver diseases, especially in China. Imaging is an indispensable tool in this filed. Mmulti-type data fusion analysis and development of multimodal treatment plans for liver cancer could become the major trend of future research in AI in liver cancer.
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Manganese superoxide dismutase (MnSOD), glutathione peroxidase-1 (GPX1), and catalase (CAT) provide the primary antioxidant defense system. Impaired antioxidant defense increases oxidative stress and contributes to the development of type 2 diabetes and diabetic cardiovascular disease (CVD). We preformed a case-control study in Chinese type 2 diabetes patients, to determine if the MnSOD Val16Ala (TâC), GPX1 Pro198Leu (CâT), and CAT -262C/T (CâT) functional polymorphisms contribute to the development of type 2 diabetes or diabetic CVD. Patients with type 2 diabetes (n = 168) were divided into the non-CVD group (n = 83, >10 year since diagnosis) and CVD group (n = 85, history of ischemic CVD). Genotyping was performed using PCR-restriction fragment length polymorphism (PCR-RFLP) or PCR-based direct sequencing. The genotypic distribution in the non-CVD- and CVD-group and the clinical parameters in genotypic groups were not significantly different in the three polymorphic sites, respectively. Among eight genotypic combinations, the most common TT+CC+CC genotype (59.5%) was associated with higher triglyceride levels than the TT+CT+CC genotype, the second frequent one (14.9%; 1.77 ± 0.12 vs. 1.21 ± 0.11 mmol/l, P = 0.001), and all non-TT+CC+CC genotypes (40.5%; 1.77 ± 0.12 vs. 1.43 ± 0.12 mmol/l, P = 0.048). In the CVD group, significantly elevated triglyceride levels were also observed in patients with TT+CC+CC compared to patients with TT+CT+CC (2.00 ± 0.18 vs. 1.37 ± 0.16 mmol/l, P = 0.018) or non-TT+CC+CC genotypes (2.00 ± 0.18 vs. 1.65 ± 0.19 mmol/l, P = 0.070). The common MnSOD, GPX1, and CAT TT+CC+CC genotype may contribute to hypertriglyceridemia in Chinese patients with type 2 diabetes or diabetic CVD.
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Povo Asiático/genética , Doenças Cardiovasculares/genética , Catalase/genética , Complicações do Diabetes/genética , Diabetes Mellitus Tipo 2/genética , Glutationa Peroxidase/genética , Hipertrigliceridemia/genética , Polimorfismo Genético , Superóxido Dismutase/genética , Triglicerídeos/sangue , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/enzimologia , Doenças Cardiovasculares/etnologia , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China/epidemiologia , Complicações do Diabetes/sangue , Complicações do Diabetes/enzimologia , Complicações do Diabetes/etnologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/enzimologia , Diabetes Mellitus Tipo 2/etnologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/enzimologia , Hipertrigliceridemia/etnologia , Masculino , Fenótipo , Reação em Cadeia da Polimerase , Medição de Risco , Fatores de Risco , Glutationa Peroxidase GPX1RESUMO
Objective: Tumor necrosis factor (TNF), a crucial cytokine, has important research value in post-stroke neuroinflammation (PSN). We analyzed the studies that have been conducted in this area and used bibliometric methods to predict research hotspots and identify trends regarding TNF in PSN. Methods: Publications were accessed at the Science Citation Index Expanded 1975-2021 (SCI expanded), Web of Science Core Collection (WoSCC), on May 1, 2022. Additionally, software such as CiteSpace and VOSviewer were utilized for bibliometric analyses. Results: In total, 1391 original articles and reviews on TNF in PSN published from 2003 to 2021 were identified. An upward trend was observed in the number of publications on TNF in PSN. These publications were primarily from 57 countries and 1446 institutions, led by China and the United States with China leading the number of publications (NP) and the US with the number of citations (NC). The League of European Research Universities (LERU) and Journal of Neuroinflammation, respectively were the most prolific branches and journals. Zhang, John H. published the most papers and Finsen, Bente had the most cited papers. One paper by Kettenmann, H. published in 2011 reached the highest level of Global Citation Score (GCS). The keyword co-occurrence and reference co-citation analyses suggest that poststroke therapy and potential mechanistic pathways are important topics related to PSN in recent years. Reference burst detection suggests new burst hotspots after 2015, focusing on pathway modulation and discovery of therapeutic targets, suggesting a substantial development in the study of TNF in PSN research. Conclusion: The present bibliometric analysis shows a continuous trend of increasing literature related to TNF in PSN, and shows that TNF plays an important role in PSN involves multiple immune mechanisms and may contribute as a potential target for neuroprotective therapeutics after stroke. Prior to 2011, most of the research was focused on discovering the specific role of TNF in PSN, and in recent years studies have mainly targeted the exploration of the signaling pathways. Future research prospects may lie in finding key therapeutic targets in pathway of TNF in PSN.
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Pesquisa Biomédica , Acidente Vascular Cerebral , Humanos , Estados Unidos , Doenças Neuroinflamatórias , Bibliometria , Publicações , Fatores de Necrose TumoralRESUMO
The pathological damage of mesangial cells serves an important role in the occurrence and development of diabetic nephropathy. Ellagic acid has been reported to possess antioxidant, antitumor, antiviral and anti-inflammatory properties in several diseases, but the roles of ellagic acid in diabetic nephropathy are unclear. The main aim of the present study was to investigate the effect of ellagic acid on high glucose-induced mesangial cell damage. The results revealed that high glucose could induce the hyperproliferation of mesangial cells, decrease the activity of superoxide dismutase, increase the malondialdehyde content, the level of reactive oxygen species, the secretion of inflammatory factors (TNF-α, IL-1ß and IL-6) and the synthesis of extracellular matrix (Fibronectin, MMP-9 and TIMP-1) and activate the PI3K/Akt/FOXO3a signaling pathway. Ellagic acid could attenuate the injury of mesangial cells induced by high glucose in a concentration-dependent manner and its effect was consistent with that of a PI3K inhibitor (LY294002). Moreover, a PI3K agonist (740Y-P) reversed the protective effect of ellagic acid on mesangial cells induced by high glucose. In conclusion, ellagic acid protected mesangial cells from high glucose-induced injury in a concentration-dependent manner. The mechanism may be associated with ellagic acid inhibiting the activation of the PI3K/Akt signaling pathway and reducing the expression levels of downstream transcription factor FOXO3a.
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Diabetic nephropathy (DN) as a global health concern is closely related to inflammation and oxidation. Isoliquiritigenin (ISL), a natural flavonoid compound, has been demonstrated to inhibit inflammation in macrophages. Herein, we investigated the effect of ISL in protecting against the injury in STZ-induced type 1 DN and in high glucose-induced NRK-52E cells. In this study, it was revealed that the administration of ISL not only ameliorated renal fibrosis and apoptosis, but also induced the deterioration of renal function in diabetic mice. Mediated by MAPKs and Nrf-2 signaling pathways, respectively, upstream inflammatory response and oxidative stress were neutralized by ISL in vitro and in vivo. Moreover, as further revealed by the results of molecular docking, sirtuin 1 (SIRT1) binds to ISL directly, and the involvement of SIRT1 in ISL-mediated renoprotective effects was confirmed by studies using in vitro models of SIRT1 overexpression and knockdown. In summary, by reducing inflammation and oxidative stress, ISL has a significant pharmacological effect on the deterioration of DN. The benefits of ISL are associated with the direct binding to SIRT1, the inhibition of MAPK activation, and the induction of Nrf-2 signaling, suggesting the potential of ISL for DN treatment.
Assuntos
Chalconas/uso terapêutico , Hiperglicemia/tratamento farmacológico , Inflamação/complicações , Rim/lesões , Estresse Oxidativo , Sirtuína 1/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Chalconas/química , Chalconas/farmacologia , Fibrose , Rim/efeitos dos fármacos , Rim/patologia , Camundongos Endogâmicos C57BL , Modelos Moleculares , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , RatosRESUMO
The aim of the present study was to evaluate the relationship of the manganese superoxide dismutase (MnSOD) Val16Ala (V16A) polymorphism with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) in Chinese patients, a case-control study was performed. This case-control study included 172 non-diabetic (non-DM) subjects and 257 T2DM patients with or without DN. Among T2DM patients, 154 had DN [albumin excretion rate (AER) >or= 30 mg/24 h] and 103 did not (AER < 30 mg/24 h), but the latter with known diabetes duration >or=10 years. The DN patients were further divided into groups with microalbuminuria (DN-1; n = 92; 300 > AER >or= 30 mg/24 h) and overt albuminuria nephropathy (DN-2; n = 62; AER >or= 300 mg/24 h). PCR-restriction fragment length polymorphism (RFLP) was used to detect genotypes of the V16A polymorphism for all subjects. The genotypic distributions of the V16A polymorphism in non-DM and T2DM subjects were in Hardy-Weinberg equilibrium and Ala allelic frequencies did not differ (11.9% vs. 9.1%; P > 0.05). The AA+VA genotypic frequencies of DN patients were significantly lower than those of non-DN patients (11.6% vs. 24.3%; P = 0.008). Multiple logistic regression analysis revealed that except for HbA1C, triglyceride, and BMI, which were high risk factors for the development of DN, the AA+VA genotype of the MnSOD-V16A polymorphism was an independent protective factor from the development of DN (odds ratio = 0.42; 95% CI = 0.18-0.95; P = 0.037) in T2DM patients. Our results suggested that the MnSOD-V16A polymorphism is associated with decreased risk of diabetic nephropathy in Chinese patients with type 2 diabetes.
Assuntos
Alanina/genética , Diabetes Mellitus Tipo 2/genética , Nefropatias Diabéticas/genética , Polimorfismo Genético , Superóxido Dismutase/genética , Valina/genética , Idoso , Alelos , Povo Asiático , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/enzimologia , Nefropatias Diabéticas/enzimologia , Nefropatias Diabéticas/etiologia , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , RiscoRESUMO
BACKGROUND AND OBJECTIVES: High concentrations of local anesthetics may be neurotoxic for diabetic patients. Additive perineural administration of magnesium was reported to decrease the consumption of local anesthetics for nerve block. It was hypothesized that MgSO4 added to dilute ropivacaine was equianalgesic to more concentrated ropivacaine for toe amputations in diabetic patients. METHODS: Seventy diabetic patients were allocated into 3 groups: 1) perineural 200 mg MgSO4 added to 0.25% ropivacaine, 2) 0.25% ropivacaine alone, and 3) 0.375% ropivacaine alone. All patients underwent popliteal sciatic nerve block that was guided by ultrasonography using the respective regimens. Time of onset, duration of motor and sensory block were recorded. Spontaneous and evoked pain score, worst pain score, additional analgesic consumption, satisfaction score and initial time of analgesic requirement of each patient were documented up to 48 hours postoperatively. RESULTS: In comparison with 0.25% ropivacaine alone, magnesium supplement prolonged the duration of sensory block (p = 0.001), as well as better evoked pain score at 6 hour postoperatively (p = 0.001). In comparison with evoked pain score (1.6/10) in group of 0.375% ropivacaine, magnesium plus 0.25% ropivacaine presented a little higher score (2.5/10) at 6 hour postoperatively (p = 0.001), while lower worst pain score (p = 0.001) and less postoperative total analgesic consumption (p = 0.002). CONCLUSIONS: The regimen of adding 200mg MgSO4 to 0.25% ropivacaine for sciatic nerve block yields equal analgesic effect in comparison with 0.375% ropivacaine. These findings have suggested that supplemental MgSO4 could not improve analgesic quality except reducing the total amount of local anesthetics requirement in diabetic toe amputations with sciatic nerve blocks.
Assuntos
Amputação Cirúrgica , Anestésicos Locais/uso terapêutico , Pé Diabético/cirurgia , Sulfato de Magnésio/uso terapêutico , Bloqueio Nervoso/métodos , Nervo Isquiático/efeitos dos fármacos , Dedos do Pé/cirurgia , Amidas/administração & dosagem , Amidas/uso terapêutico , Amputação Cirúrgica/métodos , Anestésicos Combinados/administração & dosagem , Anestésicos Combinados/uso terapêutico , Anestésicos Locais/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RopivacainaRESUMO
BACKGROUND: The waist-to-height ratio (WHtR), a novel index that has been reported to correlate more strongly than body mass index (BMI) and waist circumference (WC) with cardiometabolic risk factors, has not been studied in Chinese individuals with normal body mass index and waist circumference. The present study compared the predictive power of WHtR with those of BMI and WC for such factors in non-obese Chinese, and to define optimal cutoffs of WHtR in this population. METHODS: A total of 2137 subjects aged 40-75 years were recruited. Three anthropometric indices (WHtR, BMI, and WC) were compared and the optimal cutoffs of WHtR were identified by receiver operating characteristic curve (ROC) analysis. WHtR was divided into four quartiles (WHtR-Q), and multiple linear regression analyses were used to calculate the relationship between WHtR-Q and clinical biochemical index. RESULTS: Waist-to-height ratio was more efficient than WC to identify cardiometabolic risk factors in both genders, but was only superior to BMI in females. WHtR-Q was positively correlated with fasting plasma glucose, 2-h postprandial blood glucose, and systolic blood pressure, and negatively connected with high density lipoprotein cholesterol in both genders after controlling for age, current smoking and drinking, moderate-intensity physical activity, daily sedentary time, daily screen time and menopause (only for females). The optimal cutoffs of WHtR for detecting cardiometabolic risk factors were 0.47 in males and 0.51 in females. CONCLUSION: Waist-to-height ratio might be an effective index to identify cardiometabolic risk factors in Chinese with normal BMI and WC, particularly in females.