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1.
Front Genet ; 13: 686739, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35601482

RESUMO

Objective: This study aimed to exploit cellular heterogeneity for revealing mechanisms and identifying therapeutic targets for Parkinson's disease (PD) via single-cell transcriptomics. Methods: Single-cell RNA sequencing (scRNA-seq) data on midbrain specimens from PD and healthy individuals were obtained from the GSE157783 dataset. After quality control and preprocessing, the principal component analysis (PCA) was presented. Cells were clustered with the Seurat package. Cell clusters were labeled by matching marker genes and annotations of the brain in the CellMarker database. The ligand-receptor networks were established, and the core cell cluster was selected. Biological functions of differentially expressed genes in core cell clusters were analyzed. Upregulated marker genes were identified between PD and healthy individuals, which were measured in 18 PD patients' and 18 healthy individuals' blood specimens through RT-qPCR and Western blotting. Results: The first nine PCs were determined, which can better represent the overall change. Five cell clusters were identified, including oligodendrocytes, astrocytes, neurons, microglial cells, and endothelial cells. Among them, endothelial cells were the core cell cluster in the ligand-receptor network. Marker genes of endothelial cells possessed various biological functions. Among them, five marker genes (ANGPT2, APOD, HSP90AA1, HSPA1A, and PDE1C) were upregulated in PD patients' than in healthy individuals' endothelial cells, which were confirmed in PD patients' than in healthy individuals' blood specimens. Conclusion: Our findings revealed that the cellular heterogeneity of PD and endothelial cells could play a major role in cell-to-cell communications. Five upregulated marker genes of endothelial cells could be underlying therapeutic targets of PD, which deserve more in-depth clinical research.

2.
Bioengineered ; 13(2): 2217-2225, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35030973

RESUMO

Diabetes mellitus is a metabolic disease caused by defective insulin secretion and/or insulin action. And insulin is the main hormone released by the pancreatic ß-cells. Diosgenin (DG) is a phytochemical with pharmacological activity that increases insulin secretion in streptozotocin (STZ)-induced pancreatic ß-cells of diabetic rats. In this paper, we investigated the effect and mechanism of DG on cell apoptosis and dysfunction in STZ-induced pancreatic ß-cells. Cell viability was detected by CCK-8, apoptosis by flow cytometry, and apoptosis-related protein expression by Western blot. Western blot and RT-qPCR were performed to detect the expression of related genes. The results showed that in STZ-induced INS-1 cells, DG could improve cell viability, inhibit apoptosis, attenuate oxidative stress levels and increase insulin secretion. Notably, PDE3B was highly expressed in STZ-induced INS-1 cells, while DG could significantly inhibit PDE3B expression in a dose-dependent manner. More importantly, overexpression PDE3B remarkably reversed the effect of DG on STZ-induced INS-1 cells. It is thus clear that DG might inhibit STZ-treated pancreatic ß-cell apoptosis and reduce dysfunction via downregulating PDE3B, which provided a more reliable theoretical basis for the treatment of diabetes mellitus with DG.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Apoptose/efeitos dos fármacos , Nucleotídeo Cíclico Fosfodiesterase do Tipo 3/metabolismo , Células Secretoras de Insulina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estreptozocina/toxicidade , Serina-Treonina Quinases TOR/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Animais , Apoptose/genética , Linhagem Celular Tumoral , Nucleotídeo Cíclico Fosfodiesterase do Tipo 3/genética , Ratos , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/genética
3.
J Ethnopharmacol ; 288: 114968, 2022 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-35007681

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The dispensing granules of traditional Chinese medicines (TCMs) is an innovative form of medicinal material for TCMs decoction, which is gradually recognized in the clinic due to being suitable for production on a large scale and convenient to take for patients. However, the quality control of TCMs dispensing granules is being challenged, because they contain too many unrevealed hydrophilic components. AIM OF THE STUDY: Here, the dispensing granules produced from the rhizome of Atractylodes macrocephala (Baizhu dispensing granules), were explored as a case to explore the quality markers correlated to the clinical efficacy of TCMs dispensing granules by a comprehensive strategy of integrating chemical profiling, network pharmacology, and chemometric analysis. MATERIALS AND METHODS: First, the chemical profiling of Baizhu dispensing granules was characterized by using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Subsequently, the potential active components responsible for the efficacy of Baizhu dispensing granules were screened via network pharmacology, and the ultra-performance liquid chromatography coupled with photodiode array detector (UPLC-PDA) method was developed for quantitative analysis of the potential active components in 26 batches of Baizhu dispensing granules. Finally, the quality markers of Baizhu dispensing granules were deciphered based on content variations of potential active components and chemometric analysis. RESULTS: A total of 69 components were identified from Baizhu dispensing granules. Network pharmacology analysis further revealed that eight of them including five caffeoylquinic acids (31, 32, 36, 42, 44) and three sesquiterpenoids (63, 67, 76) were intimately connected to the core targets of dyspepsia, enteritis, gastritis and immunity. The contents of eight components differed greatly among 26 batches of Baizhu dispensing granules. Chlorogenic acid (31), cryptochlorogenic acid (32) and atractylenolide III (63) have higher concentrations and make great contributions to distinguish different batches of the Baizhu dispensing granules based on principal component analysis (PCA) and orthogonal partial least squares-discriminate analysis (OPLS-DA), and could be used as the quality markers of Baizhu dispensing granules. CONCLUSIONS: Our study defined the quality markers of Baizhu dispensing granules, which will benefit further investigation on the quality evaluation of TCMs dispensing granules containing Baizhu. The strategy used in this study will be helpful for discovering the quality markers of other TCMs dispensing granules.


Assuntos
Atractylodes/química , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa/normas , Controle de Qualidade , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/normas , Humanos , Espectrometria de Massas , Análise de Componente Principal , Rizoma
4.
J Clin Ultrasound ; 50(2): 211-215, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34812503

RESUMO

Gliomatosis peritonei (GP), almost exclusively linked to mature or immature ovarian teratoma, is a very rare disease. To the best of our knowledge, reports on the complete clinical course and imaging features of ovarian mature teratoma with GP are extremely rare. We present a case of ovarian mature teratoma with GP in a 9-year-old girl admitted to the emergency department for a 2-month history of a large abdominal mass found accidentally. Carcinoembryonic antigen and cancer antigen 125 levels were elevated. CT scans suggested a large mass with mild enhancement, and an immature teratoma derived from the left ovary with ascites was diagnosed by ultrasound. Subsequently, left ovarian tumor resection and omentectomy were performed, and a solid cystic mass accompanied by massive ascites and numerous white to grayish nodules was identified on the left ovary. The pathology results revealed a mature teratoma with GP. The patient had good postoperative recovery, and her serum tumor marker levels decreased to normal at the 3-month follow-up.


Assuntos
Neoplasias Ovarianas , Neoplasias Peritoneais , Teratoma , Criança , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/cirurgia , Teratoma/diagnóstico por imagem , Teratoma/cirurgia , Tomografia Computadorizada por Raios X
5.
J Affect Disord ; 297: 8-17, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34666115

RESUMO

Depression is a prevalent, life-threatening, and highly recurrent psychiatric illness. Several studies have shown that depression is associated with endogenous metabolites and the gut microbiota. However, it is unclear whether metabolites in different gut tissues play a role in the pathogenesis of depression and whether the gut microbiota has an impact on depression. Here, we investigated the metabolic signatures in the jejunum, ileum, and colorectum using metabolomics and explored the influence of the gut microbiota on both the development of chronic variable stress (CVS)-induced depression rat model and variations in gut tissue metabolites using a gnotobiotic rat model. The results showed that CVS induced disturbances in gut metabolites (29 differential metabolites) and had different effects on the different segments. When CVS rats were treated with antibiotics, depression-like ethological disorders disappeared, and the decreased catecholamine levels almost normalized. The depression recovery was attributed to the influence of antibiotics on the gut microbiota, especially inhibiting Clostridiaceae (F1), Candidatus arthromitus (G2), Lactobacillus (G6), and elevating Pseudomonadaceae (F6). Moreover, 16 of 29 varied metabolites in CVS rats were reversed with antibiotic treatment. Among them, 12 increased metabolites were decreased, suggesting a trigger for depression. However, four decreased metabolites were increased, indicating a potential therapeutic effect on depression. Based on the Pearson's correlation analysis, hypoxanthine, 3-hydroxypristanic acid, threonic acid, and L-carnitine were strongly associated with F6, F1, G2, and G6, which are involved in the development and prevention of depression. These findings provide a possibility for further exploration of the pathogenesis and prevention of depression.


Assuntos
Microbioma Gastrointestinal , Animais , Antibacterianos , Depressão/prevenção & controle , Lactobacillus , Metabolômica , Ratos
6.
Math Biosci Eng ; 19(1): 1-33, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34902978

RESUMO

Since the outbreak of COVID-19 in Wuhan, China in December 2019, it has spread quickly and become a global pandemic. While the epidemic has been contained well in China due to unprecedented public health interventions, it is still raging or not yet been restrained in some neighboring countries. Chinese government adopted a strict policy of immigration diversion in major entry ports, and it makes Suifenhe port in Heilongjiang Province undertook more importing population. It is essential to understand how imported cases and other key factors of screening affect the epidemic rebound and its mitigation in Heilongjiang Province. Thus we proposed a time switching dynamical system to explore and mimic the disease transmission in three time stages considering importation and control. Cross validation of parameter estimations was carried out to improve the credibility of estimations by fitting the model with eight time series of cumulative numbers simultaneous. Simulation of the dynamics shows that illegal imported cases and imperfect protection in hospitals are the main reasons for the second epidemic wave, the actual border control intensities in the province are relatively effective in early stage. However, a long-term border closure may cause a paradox phenomenon such that it is much harder to restrain the epidemic. Hence it is essential to design an effective border reopening strategy for long-term border control by balancing the limited resources on hotel rooms for quarantine and hospital beds. Our results can be helpful for public health to design border control strategies to suppress COVID-19 transmission.


Assuntos
COVID-19 , China/epidemiologia , Emigração e Imigração , Humanos , Projetos de Pesquisa , SARS-CoV-2
7.
Artigo em Inglês | MEDLINE | ID: mdl-34512784

RESUMO

BACKGROUND: Cinnamic acid (CA) has been shown to have many beneficial effects including regulating lipid metabolism and reducing obesity. However, its effect on nonalcoholic fatty liver disease (NAFDL) has not been investigated in detail. Thus, we performed this study in order to explore CA's effect on hepatic lipid metabolism and the underlying mechanisms. METHOD: Oleic acid (OA) was used to induce lipid accumulation in HepG2 cells. After coincubation with CA, the cells were stained with oil red O and the triglyceride (TG) content was assessed. Key genes in lipogenesis and fatty acid oxidation pathways were tested. Additionally, db/db and wt/wt mice were divided into three groups, with the wt/wt mice representing the normal group and the db/db mice being divided into the NAFLD and CA groups. After 4 weeks of oral treatment, all mice were sacrificed and the blood lipid profile and liver tissues were assessed. RESULTS: CA treatment reduced the lipid accumulation in HepG2 cells and in db/db mouse livers. ACLY, ACC, FAS, SCD1, PPARγ, and CD36 were significantly downregulated, while CPT1A, PGC1α, and PPARα were significantly upregulated. CONCLUSION: CA's therapeutic effect on NAFLD may be attributed to its ability to lower hepatic lipid accumulation, which is mediated by suppression of hepatic lipogenesis and fatty acid intake, as well as increased fatty acid oxidation.

8.
Int J Med Sci ; 18(14): 3171-3181, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34400887

RESUMO

Objective: The pancreatic endocrinal system dominates the regulation of blood glucose levels in vivo, and the dysfunction of pancreatic endocrine ß-cells is a major cause of the occurrence and development of Type 2 diabetes (T2D). Although microRNA (miRNA) have been found to be key regulators of pancreatic ß-cells proliferation, differentiation and apoptosis, the underlying mechanism remains enigmatic. The aim of this study was to identify several novel miRNAs which might be involved in the etiopathogenesis of diabetic ß-cells dysfunction. Methods: The miRNA expression profiles in the pancreas of high-fat diet (HFD) fed Zucker diabetic fatty (ZDF) rats and Zucker lean (ZL) rats feed with normal-fat diet (NFD) were detected by using miRNA microarray chip, and individually verified the most significant factors by quantitative real-time polymerase chain reaction (qRT-PCR) assay. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to predict the target genes related to each of the identified miRNAs and the functions of these target genes in different metabolic signaling pathways. Results: Compared with the ZL rats, a total of 24 differentially expressed miRNAs were detected in ZDF rats. Among which miR-34a-5p and miR-452-5p were the most significantly up-regulated and down-regulated respectively. These miRNAs have not been reported in rats' pancreas before. By GO and KEGG enrichment analyses, we found that miR-34a-5p could negatively regulate pancreatic ß-cell proliferation through the involvement of Wnt signaling pathway. In addition, it was also found to regulate insulin secretion through the insulin signaling pathway to modulate blood glucose levels. At the same time, miR-452-5p was found to positively regulate the activity of the key rate-limiting enzyme branched-chain α-keto acid dehydrogenase-ß (BCKDHB) in the catabolism of branched chain amino acids (BCAA), leading to mitochondrial dysfunction in pancreatic ß-cells. Conclusions: miR-34a-5p and miR-452-5p were identified as the novel regulators of pancreatic endocrine dysfunction. These miRNAs might have the potential to be utilized as the new predictive biomarkers for the diagnosis of the occurrence and development of T2D, as well as the therapeutic targets for T2D treatment.


Assuntos
Diabetes Mellitus Tipo 2/genética , Ilhotas Pancreáticas/fisiopatologia , MicroRNAs/metabolismo , Animais , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/fisiopatologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Humanos , Ilhotas Pancreáticas/patologia , Masculino , Ratos , Ratos Zucker
9.
Biomed Res Int ; 2021: 6644827, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33834070

RESUMO

OBJECTIVE: This study is aimed at understanding the molecular mechanisms and exploring potential therapeutic targets for atrial fibrillation (AF) by multiomics analysis. METHODS: Transcriptomics and methylation data of AF patients were retrieved from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) and differentially methylated sites between AF and normal samples were screened. Then, highly expressed and hypomethylated and lowly expressed and hypermethylated genes were identified for AF. Weighted gene coexpression network analysis (WGCNA) was presented to construct AF-related coexpression networks. 52 AF blood samples were used for whole exome sequence. The mutation was visualized by the maftools package in R. Key genes were validated in AF using independent datasets. RESULTS: DEGs were identified between AF and controls, which were enriched in neutrophil activation and regulation of actin cytoskeleton. RHOA, CCR2, CASP8, and SYNPO2L exhibited abnormal expression and methylation, which have been confirmed to be related to AF. PCDHA family genes had high methylation and low expression in AF. We constructed two AF-related coexpression modules. Single-nucleotide polymorphism (SNP) was the most common mutation type in AF, especially T > C. MUC4 was the most frequent mutation gene, followed by PHLDA1, AHNAK2, and MAML3. There was no statistical difference in expression of AHNAK2 and MAML3, for AF. PHLDA1 and MUC4 were confirmed to be abnormally expressed in AF. CONCLUSION: Our findings identified DEGs related to DNA methylation and mutation for AF, which may offer possible therapeutic targets and a new insight into the pathogenesis of AF from a multiomics perspective.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/genética , Epigênese Genética , Genômica , Terapia de Alvo Molecular , Idoso , Caderinas/genética , Caderinas/metabolismo , Metilação de DNA/genética , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Masculino , Mutação/genética , Reprodutibilidade dos Testes , Sequenciamento Completo do Exoma
10.
Drug Des Devel Ther ; 15: 1577-1594, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33883881

RESUMO

BACKGROUND: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). The inflammatory response plays a critical role in DN. ZiShenWan (ZSW) is a classical Chinese medicinal formula with remarkable clinical therapeutic effects on DN, but its pharmacological action mechanisms remain unclear. AIM: In this study, a network pharmacology approach was applied to investigate the pharmacological mechanisms of ZSW in DN therapy. Based on the results of network analysis, the core targets and signaling pathways related to anti-inflammatory effect were verified via experiments in vivo. METHODS: The candidate chemical ingredients of ZSW as well as its putative targets and known therapeutic targets of DN were acquired from appropriate databases. The "herb-ingredient-target" network for ZSW in DN treatment was established. The protein-protein interaction (PPI) network of potential targets was constructed to screen the core targets. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. In addition to biochemical and pathological indicators, the core targets and signaling pathways associated with inflammation were partially validated in db/db mice at molecular level. RESULTS: A total of 56 active ingredients in ZSW and 166 DN-related targets were selected from databases. A high proportion of core targets and top signaling pathways participate in inflammation. ZSW markedly alleviated renal injuries pathologically and regulated related biomarkers. In particular, ZSW significantly inhibited the exaggerated release of inflammatory cytokines such as interleukin (IL)-1ß, IL-6, tumor necrosis factor receptor (TNF)-ɑ, and monocyte chemotactic protein (MCP)-1 as well as regulating p38 mitogen-activated protein kinases (MAPK) and phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) signaling pathways in db/db mice. CONCLUSION: This study first comprehensively investigated the active ingredients, potential targets, and molecular mechanism of ZSW as a therapy for DN. ZSW achieved renoprotective effects in DN via regulation of multiple targets and signaling pathways, especially by alleviating inflammation. Results indicate that ZSW is a promising multi-target therapeutic approach for DN treatment.


Assuntos
Anti-Inflamatórios/análise , Anti-Inflamatórios/farmacologia , Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/farmacologia , Administração Oral , Animais , Anti-Inflamatórios/administração & dosagem , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Nefropatias Diabéticas/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos
11.
Biomed Res Int ; 2021: 6616434, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33791366

RESUMO

OBJECTIVE: In this study, we aimed to identify critical genes and pathways for multiple brain regions in Parkinson's disease (PD) by weighted gene coexpression network analysis (WGCNA). METHODS: From the GEO database, differentially expressed genes (DEGs) were separately identified between the substantia nigra, putamen, prefrontal cortex area, and cingulate gyrus of PD and normal samples with the screening criteria of p value < 0.05 and ∣log2fold change (FC) | >0.585. Then, a coexpression network was presented by the WGCNA package. Gene modules related to PD were constructed. Then, PD-related DEGs were used for construction of PPI networks. Hub genes were determined by the cytoHubba plug-in. Functional enrichment analysis was then performed. RESULTS: DEGs were identified for the substantia nigra (17 upregulated and 52 downregulated genes), putamen (317 upregulated and 317 downregulated genes), prefrontal cortex area (39 upregulated and 72 downregulated genes), and cingulate gyrus (116 upregulated and 292 downregulated genes) of PD compared to normal samples. Gene modules were separately built for the four brain regions of PD. PPI networks revealed hub genes for the substantia nigra (SLC6A3, SLC18A2, and TH), putamen (BMP4 and SNAP25), prefrontal cortex area (SNAP25), and cingulate gyrus (CTGF, CDH1, and COL5A1) of PD. These DEGs in multiple brain regions were involved in distinct biological functions and pathways. GSEA showed that these DEGs were all significantly enriched in electron transport chain, proteasome degradation, and synaptic vesicle pathway. CONCLUSION: Our findings revealed critical genes and pathways for multiple brain regions in PD, which deepened the understanding of PD-related molecular mechanisms.


Assuntos
Encéfalo/metabolismo , Bases de Dados de Ácidos Nucleicos , Regulação para Baixo , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Regulação para Cima , Encéfalo/patologia , Humanos , Doença de Parkinson/genética , Doença de Parkinson/patologia
12.
J Clin Ultrasound ; 49(6): 602-604, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33675548

RESUMO

Although gastrointestinal polyps are a common disease, appendiceal orifice polyps are rare and usually found incidentally during autopsy or surgery. Data on the sonographic features of appendiceal orifice polyps in children are limited. We describe the sonographic features of appendiceal orifice polyps in two children.


Assuntos
Apêndice/diagnóstico por imagem , Pólipos/diagnóstico por imagem , Apêndice/patologia , Criança , Feminino , Humanos , Masculino , Ultrassonografia
13.
Sci Rep ; 11(1): 6401, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33737640

RESUMO

In a mouse model of Graves' disease (GD), diosgenin has been shown to have a therapeutic effect on GD by alleviating goitre. However, research on the effect of diosgenin on autoimmune thyroiditis (AIT) is lacking. In this study, transcriptomics was used to comprehensively analyse the protective effect of diosgenin against AIT in rats and the possible mechanism. The results showed that in the diosgenin-intervention group, compared to the model group, the expression of serum triiodothyronine, thyroxine, free triiodothyronine, and free thyroxine was decreased and that of thyroid-stimulating hormone was increased; these changes were accompanied by the downregulation of thyroglobulin, TSH receptor antibody and thyroid peroxidase expression in serum. Furthermore, transcriptome detection, RT-qPCR and immunohistochemistry verification revealed that in thyroid tissue, the relative mRNA and protein expression of cyclic adenosine 3',5'-monophosphate (cAMP), protein kinase A (PKA) and cAMP response element-binding protein (Creb) were increased and the mRNA expression of S100 calcium-binding protein A9 (S100A9) was decreased in the diosgenin groups. In summary, diosgenin alleviates the development of AIT, possibly via the activation of the cAMP/PKA/Creb pathway and downregulation of S100A9 gene expression.


Assuntos
Calgranulina B/sangue , Diosgenina/farmacologia , Tireoidite Autoimune/tratamento farmacológico , Transcriptoma/genética , Animais , AMP Cíclico/sangue , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/sangue , Proteínas Quinases Dependentes de AMP Cíclico/sangue , Modelos Animais de Doenças , Humanos , Iodeto Peroxidase/sangue , Masculino , Ratos , Receptores da Tireotropina/sangue , Tireoglobulina/sangue , Tireoidite Autoimune/sangue , Tireoidite Autoimune/genética , Tireoidite Autoimune/patologia , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue
14.
Front Endocrinol (Lausanne) ; 12: 627950, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33767670

RESUMO

Background: Pre-clinical research studies have shown that Madecassoside (MA) has favorable therapeutic effects on arthritis, acne, vitiligo and other diseases. However, the effects of MA on obesity have not yet been studied. This study mainly aimed to investigate the effects of MA in protecting against obesity and its underlying mechanism in reducing obesity. Methods: Obese diabetic KKay/TaJcl mice model was adopted to the study. The body weight of all animals was recorded daily, and the blood glucose, blood lipid, and serum aminotransferase levels were examined, respectively. The expression of P-AMPK, SIRT1, P-LKB1, P-ACC, and P-HSL in abdominal fat, mesenteric fat, and epididymal fat was measured by western blotting, and the levels of PPARα, CPT1a, PGC-1α, UCP-1, Cidea, Cox7a1, and Cox8b were examined by real-time quantitative PCR (RT-qPCR). Results: The results revealed that the body weight of the mice in MA group was significantly reduced, and the body mass index (BMI) showed significant difference between the two groups after 8 weeks of MA treatment. Further research revealed that it affected the mesenteric fat and epididymis fat by activating SIRT1/AMPK signaling pathway, and then promoted fatty acid oxidation of epididymal fat (PPARα ↑, CPT1a↑, and PGC-1α↑). Last but not the least, it also promoted the expression of UCP-1 and stimulated thermoregulatory genes (Cidea, Cox7a1, and Cox8b) in brown fat and mesenteric fat. Conclusions: Taken together, these findings suggest that MA can inhibit the weight gain in obese diabetic mice, and reduce triglyceride levels, inhibit lipogenesis of mesenteric fat, promote epididymal fat lipolysis and fatty acid oxidation. Furthermore, MA treatment might promote mesenteric fat browning and activate mitochondrial function in brown fat as well as mesenteric fat.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Regulação da Expressão Gênica , Transdução de Sinais , Sirtuína 1/metabolismo , Termogênese/genética , Triterpenos/farmacologia , Ganho de Peso/genética , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Glicemia/metabolismo , Índice de Massa Corporal , Carboidratos , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Epididimo/efeitos dos fármacos , Epididimo/metabolismo , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Ácidos Graxos/metabolismo , Comportamento Alimentar/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Lipólise/efeitos dos fármacos , Lipólise/genética , Masculino , Mesentério/metabolismo , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Oxirredução , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Termogênese/efeitos dos fármacos , Triglicerídeos/sangue , Ganho de Peso/efeitos dos fármacos
15.
Nutr Res ; 87: 57-69, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33601215

RESUMO

Although mangiferin has a number of documented beneficial effects, there are no systematic reviews or meta-analyses of its effects in diabetic animal models. To investigate the effects of oral administration of mangiferin on blood glucose levels, body weight, and total cholesterol and triglycerides levels in diabetic animal models, a meta-analysis was conducted and the underlying mechanisms were reviewed. Studies from 6 databases (PubMed, Web of Science, Embase, Cochrane Library, and CNKI (China National Knowledge Infrastructure), and Wanfang Med) were searched from inception to April 2020. After article screening, a total of 19 articles were included in this meta-analysis. The meta-analysis was performed using RevMan 5.3 and STATA 14.0 software. The overall pooled estimate of standardized mean difference (SMD) of mangiferin's effect on blood glucose was -1.27 (95% confidence interval [CI]: -1.71, -0.82, P < .00001). Body weight increased in lean diabetic animals with an SMD of 1.41 (95% CI: 0.57, 2.25; P = .001), while it decreased in obese diabetic animals with an SMD of -0.92 (95% CI: -1.69, -0.14; P = .02). Mangiferin intake reduced serum total cholesterol and triglycerides levels with SMDs of -1.02 (95% CI: -1.43, -0.61; P < .001) and -1.24 (95% CI: -1.70, -0.79; P < .001), respectively. The meta-analysis suggests that oral intake of mangiferin has a significant antidiabetic effect in animal models, and the systematic review suggested that this function might be attributed to its anti-inflammatory and antioxidative properties, as well as to its function of improving glycolipid metabolism and enhancing insulin signaling.


Assuntos
Diabetes Mellitus Experimental/dietoterapia , Diabetes Mellitus/dietoterapia , Suplementos Nutricionais , Hipoglicemiantes/administração & dosagem , Xantonas/administração & dosagem , Animais , Glicemia/análise , Peso Corporal , Colesterol/sangue , Diabetes Mellitus Tipo 2/dietoterapia , Dieta Hiperlipídica , Feminino , Masculino , Obesidade , Triglicerídeos/sangue
16.
J Clin Ultrasound ; 49(3): 269-273, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32954508

RESUMO

Gastrointestinal (GI) venous malformations are extremely rare. Such malformations present in the pediatric age group and can occur anywhere in the digestive tract (esophagus, stomach, small or large intestine, anus, and mesentery). We present the sonographic findings of three cases of pediatric GI venous malformation. Sonography is an important diagnostic method in pediatric GI venous malformations.


Assuntos
Trato Gastrointestinal/irrigação sanguínea , Malformações Vasculares/diagnóstico por imagem , Criança , Trato Gastrointestinal/diagnóstico por imagem , Humanos , Masculino , Ultrassonografia
17.
J Cell Mol Med ; 25(1): 367-382, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33215869

RESUMO

LLKL, a new traditional Chinese medicine formula containing Edgeworthia gardneri (Wall.) Meisn., Sibiraea angustata and Crocus sativus L. (saffron), was designed to ameliorate type 2 diabetes mellitus. Despite the therapeutic benefits of LLKL, its underlying mechanisms remain elusive. This study evaluated the LLKL anti-diabetic efficacy and its effect on gut microbiota to elucidate its mechanism of action in Zucker diabetic fatty rats. We found that administration of different LLKL concentrations (4.68, 2.34 and 1.17 g/kg/d) improved several diabetic parameters after a 6-week treatment. Moreover, LLKL modulated gut microbiota dysbiosis, increased the expression of occluding and maintained intestinal epithelial homeostasis, leading to a reduction in LPS, TNF-α and IL-6 levels. Hepatic transcriptomic analysis showed that the Toll-like receptor signalling pathway was markedly enriched by LLKL treatment. RT-qPCR results validated that LLKL treatment decreased the expressions of TLR4, MyD88 and CTSK. Furthermore, a gene set enrichment analysis indicated that LLKL enhanced the insulin signalling pathway and inhibited glycerolipid metabolism and fatty acid metabolism, which were verified by the liver biochemical analysis. These findings demonstrate that LLKL ameliorates hyperglycaemia, modulates the gut microbiota and regulates the gut-liver axis, which might contribute to its anti-diabetic effect.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Microbioma Gastrointestinal/fisiologia , Hiperglicemia/tratamento farmacológico , Hiperglicemia/fisiopatologia , Hipoglicemiantes/uso terapêutico , Medicina Tradicional Chinesa/métodos , Extratos Vegetais/uso terapêutico , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Ratos , Ratos Zucker , Receptores Toll-Like/metabolismo
18.
Front Endocrinol (Lausanne) ; 12: 794568, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35178026

RESUMO

Objective: This study was aimed to investigate the effects of JiaYanKangTai (JYKT) on regulating interleukin-17 (IL-17) signaling in rats with autoimmune thyroiditis. Methods: Lewis rats were administrated with JYKT for eight weeks after a seven-week subcutaneous injection of thyroglobulin with adjuvant and feeding iodine water. Ultrasonography was performed and total volume of thyroid was calculated. The expressions of autoantibodies and hormones were detected. Morphological changes of thyroid were observed. Metabolomics profile and metabolic network analysis were conducted. IL-17 signaling was detected by polymerase chain reaction and immunohistochemistry separately. Results: JYKT reduced the mean volumes of thyroid, decreased both levels of TPOAb and TGAb, and alleviated lymphocytic infiltration of the thyroid. Metabolic network analysis of metabolomics proved IL-17 signaling pathway as a critical pathway in JYKT administration for autoimmune thyroiditis. JYKT downregulated expressions of IL-17A, TRAF6, p-ERK1/2 and TNF-α. Conclusion: JYKT alleviated inflammatory lesions of experimental autoimmune thyroiditis by regulating IL-17 signaling.


Assuntos
Tireoidite Autoimune , Animais , China , Interleucina-17 , Medicamentos sem Prescrição , Ratos , Ratos Endogâmicos Lew , Tireoidite Autoimune/tratamento farmacológico
19.
Front Nutr ; 8: 794841, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35087857

RESUMO

Cinnamic acid (AC) and cinnamic aldehyde (AL) are two chemicals enriched in cinnamon and have been previously proved to improve glucolipid metabolism, thus ameliorating metabolic disorders. In this study, we employed transcriptomes and proteomes on AC and AL treated db/db mice in order to explore the underlying mechanisms for their effects. Db/db mice were divided into three groups: the control group, AC group and AL group. Gender- and age-matched wt/wt mice were used as a normal group. After 4 weeks of treatments, mice were sacrificed, and liver tissues were used for further analyses. Functional enrichment of differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. DEPs were further verified by parallel reaction monitoring (PRM). The results suggested that AC and AL share similar mechanisms, and they may improve glucolipid metabolism by improving mitochondrial functions, decreasing serotonin contents and upregulating autophagy mediated lipid clearance. This study provides an insight into the molecular mechanisms of AC and AL on hepatic transcriptomes and proteomes in disrupted metabolic situations and lays a foundation for future experiments.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33123206

RESUMO

OBJECTIVE: The aim of this study was to review existing evidence on the efficiency and safety of Chinese herbal medicine for the treatment of prediabetes. METHODS: Randomized controlled trials (RCTs) of Chinese herbal medicine (CHM) to treat prediabetes were searched in the following databases from their inception date onwards until 2 May 2020: MEDLINE, Cochrane, EMBASE, Web of Science, EBSCO, CINAHL, CNKI, VIP database, CBM, and Wanfang database. Quality assessment of included trials was accessed according to the guidance in Cochrane. Researchers independently assessed the validity of included trials and extracted outcome data for synthesis. RevMan 5.3 was used for the meta-analysis. RESULTS: Twenty-two RCTs including 3923 participants were included in the study. Our findings upon the 22 RCTs showed CHM is effective in the treatment of prediabetes, which can statistically reduce the incidence of diabetes (RR = 0.48; 95% CI = (0.41, 0.57); P < 0.001), increase the incidence of normalization of prediabetes (RR = 1.76; 95% CI = (1.57, 1.96); P < 0.001), and lower FPG (MD = -0.38; 95% CI = (-0.60, -0.16); P < 0.001), 2hPG (MD = -1.13; 95% CI = (-1.60, -0.67); P < 0.001), TG (MD = -0.23; 95% CI = (-0.33, -0.13); P < 0.001), TC (MD = -0.34; 95% CI = (-0.52, -0.16); P < 0.001), and BMI (MD = -0.48; 95% CI = (-0.78, -0.18); P < 0.001) after treatment, and there was no difference of HbA1c (P > 0.05). CONCLUSION: CHM is effective for the treatment of prediabetes. CHM can statistically reduce the incidence of diabetes, increase the incidence of normalization of prediabetes, and lower the FPG, 2hPG, TG, TC, and BMI levels, but with no significant difference in HbA1c. In addition, CHM was relatively safe in clinical practice. More high-quality RCTs should be conducted to strengthen the finding.

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