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1.
Angew Chem Int Ed Engl ; 62(9): e202215891, 2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36596721

RESUMO

Trifluoromethyl-bearing 5-membered rings are prevalent in bioactive molecules, but modular approaches to these compounds by functionalization of robust C(sp3 )-H bonds in a direct and selective manner are extremely challenging. Herein we report the rhodium-catalyzed α-CF3 -α-alkyl carbene insertion into C(sp3 )-H bonds of a broad range of substrates to access 7 types of CF3 -bearing saturated 5-membered carbo- and heterocycles. The reaction is particularly effective for benzylic C-H insertion exerting good site-, diastereo- and enantiocontrol, and applicable to the synthesis of chiral CF3 analogues of bioactive molecules. Ruthenium α-CF3 -α-alkyl carbene complexes underwent stoichiometric reactions to give C-H insertion products, lending evidence for the involvement of metal α-CF3 -α-alkyl carbene species in the catalytic cycle. DFT calculations revealed that the π⋅⋅⋅π attraction and intra-carbene C-H⋅⋅⋅F hydrogen bond elucidate the origin of selectivity of the benzylic C-H insertion reactions.

2.
Angew Chem Int Ed Engl ; 61(21): e202200748, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35183066

RESUMO

Metal-free and metal-containing molecular trefoil knots are fascinating ensembles that are usually covalently assembled, the latter requiring the rational design of di- or multidentate/multipodal ligands as connectors. In this work, we describe the self-assembly of pentadecanuclear AuI trefoil knots [Au15 (C≡CR)15 ] from monoalkynes HC≡CR (R=9,9-X2 -fluorenyl with X=nBu, n-hexyl) and [AuI (THT)Cl]. Hetero-bimetallic counterparts [Au9 M6 (C≡CR)15 ] (M=Cu/Ag) were self-assembled by reactions of [Au15 (C≡CR)15 ] with [Cu(MeCN)4 ]+ /AgNO3 and HC≡CR. The type of pentadecanuclear trefoil knots described herein is characterized by X-ray crystallography, 2D NMR and HR-ESI-MS. [Au9 Cu6 (C≡CR)15 ] is relatively stable in hexane; its excited state properties were investigated. DFT calculations revealed that non-covalent metal-metal and metal-ligand interactions, together with longer alkyl chain-strengthened inter-ligand dispersion interactions, govern the stability of the trefoil knot structures.

3.
Angew Chem Int Ed Engl ; 59(37): 16202-16208, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32558142

RESUMO

A transition-metal-free C(sp2 )-C(sp2 ) bond formation reaction by the cross-coupling of diazo quinones with catechol boronic esters was developed. With this protocol, a variety of biaryls and alkenyl phenols were obtained in good to high yields under mild conditions. The reaction tolerates various functionalities and is applicable to the derivatization of pharmaceuticals and natural products. The synthetic utility of the method was demonstrated by the short synthesis of multi-substituted triphenylenes and three bioactive natural products, honokiol, moracin M, and stemofuran A. Mechanistic studies and density functional theory (DFT) calculations revealed that the reaction involves attack of the boronic ester by a singlet quinone carbene followed by a 1,2-rearrangement through a stepwise mechanism.

4.
Angew Chem Int Ed Engl ; 58(45): 16297-16306, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31486262

RESUMO

Supramolecular ensembles adopting ring-in-ring structures are less developed compared with catenanes featuring interlocked rings. While catenanes with inter-ring closed-shell metallophilic interactions, such as d10 -d10 AuI -AuI interactions, have been well-documented, the ring-in-ring complexes featuring such metallophilic interactions remain underdeveloped. Herein is described an unprecedented ring-in-ring structure of a AuI -thiolate Au12 cluster formed by recrystallization of a AuI -thiolate Au10 [2]catenane from alkane solvents such as hexane, with use of a bulky dibutylfluorene-2-thiolate ligand. The ring-in-ring AuI -thiolate Au12 cluster features inter-ring AuI -AuI interactions and underwent cluster core change to form the thermodynamically more stable Au10 [2]catenane structure upon dissolving in, or recrystallization from, other solvents such as CH2 Cl2 , CHCl3 , and CH2 Cl2 /MeCN. The cluster-to-cluster transformation process was monitored by 1 H NMR and ESI-MS measurements. Density functional theory (DFT) calculations were performed to provide insight into the mechanism of the "ring-in-ring⇌ [2]catenane" interconversions.

5.
Tumour Biol ; 34(5): 3137-45, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23760979

RESUMO

Recently, stathmin 1 has been proposed to function as an oncogene based on some relevant studies in multiple types of human cancers. However, the role of stathmin 1 in gastric cancer carcinogenesis has not been elucidated yet. The aim of this study was to investigate the expression of stathmin 1 as well as its association with overall survival of gastric cancer patients. The expression of stathmin 1 was detected by real-time quantitative reverse transcription polymerase chain reaction and Western blotting in gastric cancer and adjacent nontumor tissues. In addition, stathmin 1 expression was analyzed by immunohistochemistry in paraffin samples from 210 primary gastric cancer patients. The expression levels of stathmin 1 mRNA and protein in gastric cancer tissues were both significantly higher than those in adjacent nontumor tissues. In addition, the expression of stathmin 1 is correlated with Lauren's classification, depth of invasion, lymph node metastases, and tumor node metastasis (TNM) stage (all P < 0.05). Univariate analysis showed that high stathmin 1 expression was associated with poor prognosis in gastric cancer patients (P = 0.040). Multivariate analysis demonstrated that only lymph node metastasis and TNM stage were the independent prognostic indicators for gastric cancer. Stathmin 1 expression status is not an independent prognostic factor for patients with gastric cancer. Further subgroup analysis revealed that stathmin 1 expression was significantly correlated with prognosis in diffuse type gastric cancer. This research showed that the stathmin 1 overexpression might play an important role in the pathogenesis and subsequent progression of gastric cancer. Stathmin 1 could also be a potential therapeutic target in gastric cancer, especially for diffuse type gastric cancer.


Assuntos
Adenocarcinoma/metabolismo , Expressão Gênica , Estatmina/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Estatmina/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Adulto Jovem
6.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 35(2): 155-60, 2013 Apr.
Artigo em Zh | MEDLINE | ID: mdl-23643003

RESUMO

OBJECTIVE: To investigate the change of lymphocyte subsets before and after chemotherapy in colorectal carcinoma patients. METHODS: Twenty-one peripheral blood lymphocyte subsets from 62 colorectal carcinoma patients before and after FOLFOX4(including oxaliplatin, 5-fluorouracil and leucovorin) , FOLFRI(including irinotecan, 5-fluorouracil and leucovorin) , or XELOX(including oxaliplatin and capecitabine) regimen chemotherapy were examined by flow cytometry.The differences of these lymphocyte subsets were analyzed. RESULTS: After chemotherapy, the percentages of CD3(+), CD3(+)CD8(+), CD29(+), CD4(+)CD29(+), and CD4(+)CD25(+) cells in peripheral blood of colorectal carcinoma patients increased significantly, while the percentages of CD19(+) and human leukocyte antigen(locus) DR(HLA-DR) (+) cells decreased significantly(P<0.05) .The results of subgroup analysis showed that the patients' CD3(+)CD8(+) and CD4(+)CD25(+) cells increased significantly, CD19(+) and HLA-DR(+) cells decreased significantly after FOLFOX4 regimen chemotherapy(P<0.05) ;CD3(+)CD8(+) cells increased significantly and CD19(+) cells decreased significantly after XELOX regimen chemotherapy(P<0.05) ;while after FOLFRI regimen chemotherapy, there were no significant changes in all 21 lymphocyte subsets(P>0.05) . CD3(+), CD3(+)CD8(+), memory T lymphoctye(45RO(+)) , and CD4(+)CD45RO(+) cells increased significantly(P<0.05) in patients who received no more than 4 cycles of chemotherapy. However, in patients that received 5 to 8 cycles and more than 9 cycles chemotherapy, we only found significant decrease of HLADR(+) cells and significant increase of CD29(+) cells, respectively(P<0.05) . CONCLUSIONS: The humoral immunity is attenuated after chemotherapy in colorectal carcinoma patients. FOLFOX4 may suppress the cellular immunity.Chemotherapy that is less than 4 cycles will strengthens the cellular immunity by modulating body immunity arrangement;however, along with the increase of chemotherapy cycles, the cellular immunity gradually declines in these patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/imunologia , Subpopulações de Linfócitos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD19/metabolismo , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Capecitabina , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaloacetatos
7.
Zhonghua Wai Ke Za Zhi ; 51(12): 1071-6, 2013 Dec.
Artigo em Zh | MEDLINE | ID: mdl-24499714

RESUMO

OBJECTIVE: To elucidate the necessity of para-aortic lymph nodal dissection in D2 lymphadenectomy for gastric cancer in N3 stage. METHODS: A total of 278 gastric cancer patients staged N3 who underwent gastrectomy between January 2003 and December 2007 were enrolled. There were 180 male and 98 female patients, and the patients' age were 26-93 years (median was 61 years). All patients had undergone surgical treatment. There were R0 resection in 246 cases and R1 resection in 32 cases. Lymph node dissection included D1 lymphadenectomy with 125 cases, D2 lymphadenectomy with 109 cases and D2+para-aortic lymph nodal dissection(PAND) with 44 cases. The surgical approach were total gastrectomy (98 cases) and subtotal gastrectomy (180 cases). Potential prognostic factors were analyzed. RESULTS: The lymph node metastasis of each station was high in gastric cancer patients staged N3 and 34.1% patients had the para-aortic lymph nodal metastasis. Borrmann type (HR = 1.350, 95%CI: 1.018-1.790, P = 0.037), curability (HR = 1.580, 95%CI: 1.076-2.322, P = 0.020), depth of invasion (HR = 1.697, 95%CI: 1.005-2.864, P = 0.048), metastatic lymph node ratio (HR = 1.631, 95%CI: 1.261-2.111, P = 0.000), extranodal metastasis (HR = 1.336, 95%CI: 1.027-1.738, P = 0.031), postoperative adjuvant chemotherapy (HR = 1.312, 95%CI: 1.015-1.696, P = 0.038), extent of lymphadenectomy (HR = 1.488 and 2.114, P = 0.054 and 0.000) and number of retrieved lymph node (HR = 1.503 and 2.112, P = 0.025 and 0.000) were found to be factors correlated to overall survival. In multivariate analysis, only Borrmann type (HR = 1.399, 95%CI: 1.050-1.863, P = 0.022), metastatic lymph node ratio (HR = 1.353, 95%CI: 1.016-1.802, P = 0.039) and extent of lymphadenectomy (HR = 1.725, 95%CI: 1.111-2.678, P = 0.015) were independent prognostic factors for gastric cancer patients in N3 stage. CONCLUSIONS: Patients in N3 stage should at least have 30 lymph node examined. D2 lymph node dissection plus PAND may improve the overall survival for gastric cancer patients in N3 stage.


Assuntos
Gastrectomia , Excisão de Linfonodo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida
8.
Chem Sci ; 14(38): 10602-10609, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37800003

RESUMO

Terminal Ru(v)-imido species are thought to be as reactive to group transfer reactions as their Ru(v)-oxo homologues, but are less studied. With the electron-rich corrole ligand, relatively stable and isolable Ru(v)-arylimido complexes [Ru(tBu-Cor)(NAr)] (H3(tBu-Cor) = 5,15-diphenyl-10-(p-tert-butylphenyl)corrole, Ar = 2,4,6-Me3C6H2 (Mes), 2,6-(iPr)2C6H3 (Dipp), 2,4,6-(iPr)3C6H2 (Tipp), and 3,5-(CF3)2C6H3 (BTF)) can be prepared from [Ru(tBu-Cor)]2 under strongly reducing conditions. This type of Ru(v)-monoarylimido corrole complex with S = ½ was characterized by high-resolution ESI mass spectrometry, X-band EPR, resonance Raman spectroscopy, magnetic susceptibility, and elemental analysis, together with computational studies. Under heating/light irradiation (xenon lamp) conditions, the complexes [Ru(tBu-Cor)(NAr)] (Ar = Mes, BTF) could undergo aziridination of styrenes and amination of benzylic C(sp3)-H bonds with up to 90% product yields.

9.
Genes Dis ; 10(3): 799-812, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37396503

RESUMO

Obesity plays a crucial role in the development of non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanism for the pathogenesis of obesity-associated NAFLD remains largely obscure. Although the "multiple hit" theory provides a more accurate explanation of NAFLD pathogenesis, it still cannot fully explain precisely how obesity causes NAFLD. The liver is the key integrator of the body's energy needs, receiving input from multiple metabolically active organs. Thus, recent studies have advocated the "multiple crosstalk" hypothesis, highlighting that obesity-related hepatic steatosis may be the result of dysregulated "crosstalk" among multiple extra-hepatic organs and the liver in obesity. A wide variety of circulating endocrine hormones work together to orchestrate this "crosstalk". Of note, with deepening understanding of the endocrine system, the perception of hormones has gradually risen from the narrow sense (i.e. traditional hormones) to the broad sense of hormones as organokines and exosomes. In this review, we focus on the perspective of organic endocrine hormones (organokines) and molecular endocrine hormones (exosomes), summarizing systematically how the two types of new hormones mediate the dialogue between extra-hepatic organs and liver in the pathogenesis of obesity-related NAFLD.

10.
World J Diabetes ; 14(8): 1249-1258, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37664479

RESUMO

BACKGROUND: Obesity usually causes diabetes mellitus (DM) and is a serious danger to human health. Type 2 DM (T2DM) mostly occurs along with obesity. Foodborne obesity-induced DM is caused by an excessive long-term diet and surplus energy. Bariatric surgery can improve the symptoms of T2DM in some obese patients. But different types of bariatric surgery may have different effects. AIM: To investigate the effect of bariatric surgery on glucose and lipid metabolism and liver and kidney function in rats. METHODS: Male Sprague-Dawley rats aged 6-8 wk underwent Roux-en-Y gastric bypass surgery (RYGB), sleeve gastrectomy (SG), or gastric banding (GB). Glucose and insulin tolerance tests, analyses of biochemical parameters, histological examination, western blot, and quantitative real-time polymerase chain reaction were conducted. RESULTS: In comparison to the sham operation group, the RYGB, SG, and GB groups had decreased body weight and food intake, reduced glucose intolerance and insulin insensitivity, downregulated biochemical parameters, alleviated morphological changes in the liver and kidneys, and decreased levels of protein kinase C ß/ P66shc. The effect in the RYGB group was better than that in the SG and GB groups. CONCLUSION: These results suggest that RYGB, SG and GB may be helpful for the treatment of foodborne obesity-induced DM.

11.
Metabolism ; 146: 155660, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37451670

RESUMO

BACKGROUND AND OBJECTIVES: MicroRNA-dependent regulation of hepatic lipid metabolism has been recognized recently as a key pathological mechanism contributing to the development of NAFLD. However, whether miR-32-5p (miR-32) plays a role in lipid metabolism or contributes to NAFLD remains unclear. METHODS AND RESULTS: A marked increase in miR-32 expression was observed in liver samples from patients and mice with NAFLD, as well as in palmitate-induced hepatocytes. Hepatocyte-specific miR-32 knockout (miR-32-HKO) dramatically ameliorated hepatic steatosis and metabolic disorders in high-fat diet-fed mice. Conversely, hepatic miR-32 overexpression markedly exacerbated the progression of these abnormalities. Further, combinational analysis of transcriptomics and lipidomics suggested that miR-32 was a key trigger for de novo lipogenesis in the liver. Mechanistically, RNA sequencing, luciferase assay and adenovirus-mediated downstream gene rescue assay demonstrated that miR-32 directly bound to insulin-induced gene 1 (INSIG1) and subsequently activated sterol regulatory element binding protein-mediated lipogenic gene programs, thereby promoting hepatic lipid accumulation and metabolic disorders. Notably, pharmacological administration of miR-32 antagonist significantly inhibited palmitate-induced triglyceride deposition in hepatocytes and markedly mitigated hepatic steatosis and metabolic abnormalities in obesity-associated NAFLD mice. CONCLUSION: miR-32 is an important checkpoint for lipogenesis in the liver, and targeting miR-32 could be a promising therapeutic approach for NAFLD treatment.


Assuntos
Hiperlipidemias , MicroRNAs , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Humanos , Lipogênese/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hiperlipidemias/metabolismo , Células Hep G2 , Fígado/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Dieta Hiperlipídica/efeitos adversos , Palmitatos , Camundongos Endogâmicos C57BL
12.
Cancer Immunol Immunother ; 61(6): 911-6, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22116346

RESUMO

Expression levels of VEGF and Her-2, levels of T-regulatory (Treg) cells, levels of CD3+ cells, and ratios of Th (CD4+ T cells)/Tr (Treg) cells were compared between stage I, II, III, and IV breast cancer patients (n = 120) prior to chemotherapy and healthy women (n = 30). Cells from peripheral blood were counted by flow cytometry, Her-2 and VEGF expression was detected by pathological examination, and Her-2 was detected by FISH. Breast cancer patients had more Treg cells and a lower ratio of Th/Tr cells than the healthy women. Stage IV breast cancer patients had more Treg cells and a lower ratio of Th/Tr cells than stage I, II, or III breast cancer patients. Patients positive for VEGF had a lower ratio of Th/Tr cells compared with patients negative for VEGF, and those positive for both VEGF and Her-2 also had a lower ratio of Th/Tr cells compared with patients not positive for both VEGF and Her-2. The decreased Th/Tr cells ratio indicates impaired immune function, suggesting that the stage IV breast cancer and the Her-2/VEGF-positive breast cancer patients have lower immune function.


Assuntos
Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Linfócitos T Reguladores/imunologia , Adolescente , Adulto , Idoso , Feminino , Saúde , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Receptor ErbB-2/biossíntese , Receptor ErbB-2/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/imunologia , Adulto Jovem
13.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 34(3): 234-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22776655

RESUMO

OBJECTIVE: To evaluate the CD4+CD25+ regulatory T cells (Treg) and other lymphocyte subsets in the peripheral blood of patients with advanced lung adenocarcinoma. METHODS: Peripheral blood samples were obtained from 64 patients with advanced lung adenocarcinoma (case group) and analyzed by flow cytometry. The ratios of CD4+CD25+Treg T cells and other T lymphocyte subsets in peripheral blood were compared with those from 33 healthy controls (control group). RESULTS: The percentages of CD3+ and CD3+CD4+ were (66.5±11.0)% and (37.7±10.6)% respectively in the peripheral blood of the case group, which were significantly lower than those [(72.0±6.0)% and (42.0±6.4)%] in the control group (t=-3.2,-2.4; P=0.020, 0.015, respectively). The ratio of CD4+ CD25+ Treg cells in case group (10.5±4.0)% was significantly higher than that [(8.4±3.5)%] in the control group (t=-2.2, P=0.013). CD4+/CD8+ value of case group (1.4±0.8) was significantly lower than that (1.8±0.7) in control group(t=-2.2, P=0.029). CD3+CD8+, CD8+CD28-, and CD8+CD28+ showed no significant differences (all P>0.05). Smoking, differentiation grade, and size of the tumor showed no association with the function damage of T lymphocyte subsets, while the carcino-embryonic antigen level did. CONCLUSIONS: In patients with advanced lung adenocarcinoma, Treg increases and CD4+/CD8+ decreases, suggesting remarkably suppressed immune functions. However, more research is warranted to validate the association of T cells subset dysfunction with smoking, differentiation grade, and size of tumor.


Assuntos
Adenocarcinoma/imunologia , Neoplasias Pulmonares/imunologia , Subpopulações de Linfócitos T/imunologia , Adenocarcinoma de Pulmão , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
14.
Zhonghua Wai Ke Za Zhi ; 50(11): 966-70, 2012 Nov.
Artigo em Zh | MEDLINE | ID: mdl-23302477

RESUMO

OBJECTIVE: To discuss the reasonable surgery for gastric body cancer. METHODS: From January 2001 to December 2006, the clinicopathological data of 145 patients with a tumor in the middle third of the stomach underwent radical gastric resection were analyzed retrospectively. We conducted comparative analysis for the differences in clinicopathological characteristics and prognosis between total gastrectomy (TG) and subtotal gastrectomy (STG). RESULTS: The 98 patients underwent TG, 47 received STG. There were significant differences in aspects of tumor size, depth of tumor, nodal status and TNM stage between the 2 groups. Patients with more advanced cancer were more likely to receive TG. The 5-year survival rate for TG was lower (25.5%) than STG (63.8%) (χ(2) = 11.707, P = 0.000). However, if tumor stages were stratified, there was no significant difference in the 5-year survival rate. TNM stage (P = 0.044) and histologic type (HR = 1.834, 95%CI: 1.073 - 3.135, P = 0.027) were independent prognostic factors. CONCLUSIONS: The overall survival rate of STG for gastric cancer in the middle third of the stomach is better than that of TG. If the radical resection margin can be obtained for gastric body carcinoma, STG is considered instead of TG.


Assuntos
Gastrectomia/métodos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Estômago/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida
15.
Endocrinology ; 163(6)2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35536227

RESUMO

Obesity has recently been defined as a chronic low-grade inflammatory disease. Obesity-induced inflammation of adipose tissue (AT) is an essential trigger for insulin resistance (IR) and related metabolic diseases. Although the underlying molecular basis of this inflammation has not been fully identified, there is consensus that the recruited and activated macrophages in AT are the most important culprits of AT chronic inflammation. Adipose tissue macrophages (ATMs) are highly plastic and could be polarized from an anti-inflammatory M2 to proinflammatory M1 phenotypes on stimulation by microenvironmental signals from obese AT. Many efforts have been made to elucidate the molecular signaling pathways of macrophage polarization; however, the upstream drivers governing and activating macrophage polarization have rarely been summarized, particularly regulatory messages from the AT microenvironment. In addition to adipocytes, the AT bed also contains a variety of immune cells, stem cells, as well as vascular, neural, and lymphatic tissues throughout, which together orchestrate the AT microenvironment. Here, we summarize how the aforesaid neighbors of ATMs in the AT microenvironment send messages to ATMs and thus regulate its phenotype during obesity. Deciphering the biology and polarization of ATMs in the obese environment is expected to provide a precise immunotherapy for adipose inflammation and obesity-related metabolic diseases.


Assuntos
Tecido Adiposo , Resistência à Insulina , Tecido Adiposo/metabolismo , Animais , Inflamação/metabolismo , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo
16.
Chem Sci ; 12(42): 14050-14058, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34760188

RESUMO

The photo-induced cleavage of C(sp2)-Cl bonds is an appealing synthetic tool in organic synthesis, but usually requires the use of high UV light, photocatalysts and/or photosensitizers. Herein is described a direct photo-induced chloroarene activation with UVA/blue LEDs that can be used in the reductive Heck cyclization of indoles and without the use of a photocatalyst or photosensitizer. The indole compounds examined display room-temperature phosphorescence. The photochemical reaction tolerates a panel of functional groups including esters, alcohols, amides, cyano and alkenes (27 examples, 50-88% yields), and can be used to prepare polycyclic compounds and perform the functionalization of natural product analogues in moderate to good yields. Mechanistic experiments, including time-resolved absorption spectroscopy, are supportive of photo-induced electron transfer between the indole substrate and DIPEA, with the formation of radical intermediates in the photo-induced dearomatization reaction.

17.
Zhonghua Wai Ke Za Zhi ; 48(20): 1542-5, 2010 Oct 15.
Artigo em Zh | MEDLINE | ID: mdl-21176667

RESUMO

OBJECTIVE: To analyze the clinical and pathologic influencing factors of early recurrence in patents with gastric cancer after radical gastrectomy. METHODS: Clinicopathological data of 141 patients with recurrence after curative gastrectomy for gastric cancer from January 2001 to December 2004 were analyzed retrospectively. Risk factors correlated with tumor early recurrence and survival difference between early recurrence group (< 1 year, 82 cases) and control group (1 year after, 59 cases) were assessed. RESULTS: The 1- and 3-year survival rates of in early recurrence group and control group were 36.6%, 2.4% and 100%, 45.8%, respectively (P < 0.05). The median survival time after recurrence in the two groups was 3, 5 months, respectively (P < 0.05). Univariate analysis showed that the age, tumor Borrmann type, tumor site, invasive depth, lymph node metastasis, pTNM stage, metastatic lymph node ratio, surgical procedure and intraperitoneal hyperthermic perfusion chemotherapy (IHPC) were significant factors associated with early recurrence after curative gastrectomy for gastric cancer (P < 0.05). Lymph node metastasis, metastatic lymph node ratio and IHPC were independent factors associate with early recurrence after curative gastrectomy on multivariate analysis (P < 0.05). CONCLUSIONS: The patients with early recurrence after the radical gastrectomy have a poorer survival compared with cases recur later. Lymph node metastasis, metastatic lymph node ratio and IHPC are independent factors associate with early recurrence after curative gastrectomy for gastric cancer.


Assuntos
Recidiva Local de Neoplasia/etiologia , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Gastrectomia , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/cirurgia
18.
Chem Sci ; 11(25): 6370-6382, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32874518

RESUMO

The realization of photocatalysis for practical synthetic application hinges on the development of inexpensive photocatalysts which can be prepared on a large scale. Herein an air-stable, visible-light-absorbing photoluminescent tungsten(vi) complex which can be conveniently prepared at the gram-scale is described. This complex could catalyse photochemical organic transformation reactions including borylation of aryl halides, such as aryl chloride, reductive coupling of benzyl bromides for C-C bond formation, reductive coupling of phenacyl bromides, and decarboxylative coupling of redox-active esters of alkyl carboxylic acid with high product yields and broad functional group tolerance.

19.
Mol Clin Oncol ; 10(2): 214-222, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30680197

RESUMO

In our previous study, it was demonstrated that the Stathmin1 (STMN1) is overexpressed in gastric cancer (GC) and that its high expression level is associated with tumor invasion and metastasis. Epithelial-mesenchymal transition (EMT) has also been shown to be critically involved in GC invasion and metastasis. Certain studies have indicated that STMN1 may serve an important role in the EMT process. However, the association between STMN1 expression and EMT-associated markers, as well as clinicopathological characteristics of patients with GC, remains unclear. The aim of the present study was to investigate the clinicopathological significance and prognostic value of STMN1 and EMT-associated markers in GC. The expression of STMN1 and the EMT-associated proteins E-cadherin (E-Cad) and vimentin (VIM) were analyzed by immunohistochemistry in GC and adjacent non-tumorous tissues. Associations between the expression of these markers and clinicopathological parameters were analyzed. The association between STMN1 expression and EMT-associated markers was investigated in the GC cell lines BGC-803 and SGC-7901. The results revealed that STMN1 was expressed in 63.5% of the 167 GC tissues, which was significantly higher than the percentage observed in the adjacent non-tumorous tissues (P=0.003). The STMN1 expression was demonstrated to be positively associated with the VIM levels (P=0.001) and negatively associated with the E-Cad levels (P=0.022) in GC tissues. The STMN1 expression was associated with Lauren's Classification, invasion depth, lymph node metastasis and pathological Tumor-Node-Metastasis (pTNM) stage (P<0.05). In the univariate analyses, the high E-Cad expression was a positive prognostic indicator for overall survival, whereas the high STMN1 and VIM expression was a negative indicator. COX multiple regression analysis demonstrated that the pTNM stage [hazard ratio (HR) 1.912, 95% confidence interval (CI): 1.282-2.851, P=0.001] and E-Cad expression (HR 0.403, 95% CI: 0.249-0.650, P=0.000) were independent prognostic factors. It was also revealed that the expression level of E-Cad decreased, while the expression level of VIM increased by depleting STMN1 levels in GC cells. The present results suggest that the aberrant expression of STMN1 may promote tumor progression through EMT in GC.

20.
Int J Med Mushrooms ; 20(1): 61-70, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29604913

RESUMO

This research aimed to evaluate the potential of Cordyceps sobolifera in mycelial biomass production via liquid culture and to assay the safety and determine the antioxidative and antiaging activities of Caenorhabditis elegans. A C. sobolifera isolate was cultured using the one-factor-at-a-time method to illustrate its carbon and nitrogen requirements. To assess safety, we determined the lethality, locomotion behavior, and reproduction of C. elegans cultured on a mycelial water extract (MWE) containing nematode growth medium (NGM). To investigate antiaging activity, C. elegans treated with MWE was incubated on NGM plates. The lethality was recorded throughout the whole life cycle. To identify antioxidant activity, C. elegans treated with MWE was exposed to paraquat, causing superoxide conditions. The results showed that C. sobolifera was favored by glucose and peptone as carbon and nitrogen sources, respectively. MWE was considered to be safe, as no abnormal behaviors were observed in C. elegans. Compared with nematodes pretreated with no MWE but with water instead, MWE at 1.0 mg/mL significantly prolonged the mean lifespan of C. elegans by 24%. We observed an obvious dose-effect relation between concentration and mean lifespan. The effective antioxidant activity was recorded at the high concentration of MWE. These findings demonstrate the potential antiaging and antioxidant properties of C. sobolifera as functional food and dietary supplement.


Assuntos
Antioxidantes/farmacologia , Caenorhabditis elegans/microbiologia , Cordyceps/química , Micélio/química , Animais , Biomassa , Caenorhabditis elegans/fisiologia , Cordyceps/fisiologia , Meios de Cultura , Técnicas de Cultura , Fermentação , Glucose/metabolismo , Estágios do Ciclo de Vida/efeitos dos fármacos , Micélio/fisiologia , Peptonas/metabolismo , Fatores de Tempo , Água/química
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