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1.
Pharmazie ; 74(10): 601-605, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31685085

RESUMO

Atherosclerosis (AS) is characterized by the significant accumulation of low-density lipoprotein (LDL)-cholesterol in macrophages that reside in the vessel wall and the resultant inflammatory response. Therefore, inhibition of LDL-induced inflammation is a promising interference for AS. Many traditional Chinese medicine prescriptions have been developed for AS treatment. Geniposide (GEN) is an iridoid glycoside mainly found in Gardenia jasminoides fruit. Although GEN has previously been shown to possess anti-atherosclerotic activities, its effects on the formation of macrophage-derived foam cells remain poorly characterized. In our current study, we demonstrated that GEN could significantly inhibit oxidized light-density lipoprotein (ox-LDL) induced macrophage foam cell formation and the expression of pro-inflammatory cytokines in a dose-dependent manner. In addition, treatment of GEN in bone-marrow derived macrophages repressed iNOS expression and NO expression. GEN could also alleviate ox-LDL-dependent up-regulation of CD36 expression by blocking the phosphorylation of p38 MAPK, ERK, JNK and NF-kB p65. The results of our current study demonstrate that GEN exhibits significant therapeutic effects against ox-LDA-induced foam cell formation and inflammation. Therefore, GEN is promising agent for treating AS.

2.
Atherosclerosis ; 289: 8-13, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31437611

RESUMO

BACKGROUND AND AIMS: Epidemiological evidence on the association between elevated lipoprotein (a) (Lp (a)) with risk of stroke remains inconsistent. We aimed to investigate the association between serum Lp (a) level and the risk of stroke among middle-aged and elderly Chinese. METHODS: A community-based prospective cohort study of 8500 participants aged 40 years or older was conducted in Jiading district, Shanghai, China, in 2010. The incident strokes were documented at follow-up visit during 2014-2015. RESULTS: During a mean follow-up of 5.1 years, 444 incident cases of stroke occurred. The incidences of stroke were 4.44%, 5.14% and 6.14% from the lowest to the highest serum Lp (a) tertile, respectively. A significant association between serum Lp (a) tertile and the risk of incident stroke was observed (p for trend<0.05). Compared with individuals in the lowest tertile of serum Lp (a), the multivariable adjusted hazards ratio (HR) and 95% confidence interval (CI) for incident stroke in Lp (a) tertile 3 were 1.34 (1.06-1.70). CONCLUSIONS: Serum Lp (a) concentration was associated with increased risk of incident stroke in Chinese adults.

3.
J Diabetes ; 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31170331

RESUMO

BACKGROUND: This study investigated the association between birth weight and diabetes in a Chinese population, and the effects of body mass index (BMI) and lifestyle factors in later life on this association. METHODS: Data from 49 118 participants aged ≥40 years with recalled birth weight from the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study, a nationwide population-based cohort, were used. Diabetes diagnosis was based on oral glucose tolerance tests and HbA1c measurements. Logistic regression models were used to evaluate the association of birth weight and risk of diabetes in later life. RESULTS: Increased risk of diabetes was associated with lower or higher birth weight. Compared with individuals with a birth weight of 2500 to 3499 g, the odds ratios (ORs) and 95% confidence intervals (CIs) of diabetes for individuals with a birth weight of <2500, between 3500 and 3999, and ≥4000 g were 1.28 (1.11-1.47), 1.11 (1.04-1.19), and 1.20 (1.07-1.34), respectively. Significant associations were prominent in participants with a current BMI ≥24 kg/m2 , but not detected in those with a normal BMI (OR 1.20 [95% CI 0.96-1.49], 1.11 [95% CI 0.98-1.25], and 1.10 [95% CI 0.89-1.37], respectively). Moreover, there was no increased risk of diabetes in individuals with a low birth weight but with healthy dietary habits (OR 0.94; 95% CI 0.68-1.29) or ideal physical activity (OR 1.41; 95% CI 0.97-2.04). CONCLUSIONS: A U-shaped association was observed between birth weight and the risk of diabetes. Healthy lifestyles (healthy dietary habits or ideal physical activity) may eliminate the negative effects of low birth weight in the development of diabetes, but not the effect of high birth weight.

4.
J Diabetes ; 11(11): 884-894, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30941862

RESUMO

BACKGROUND: This study examined whether resting heart rate (RHR) was associated with metabolic syndrome (MetS) and the 10-year predicted risk of cardiovascular disease in a Chinese population. METHODS: The associations of RHR with MetS and 10-year risk of atherosclerotic cardiovascular diseases (ASCVD) was examined in a cross-sectional study conducted in Shanghai, China (n = 9486). RESULTS: Compared with individuals in the lowest RHR quintile (≤71 b.p.m.), those in the highest quintile (≥91 b.p.m.) had a higher prevalence of MetS (21.2% vs 32.6%, respectively; P < 0.001). Logistic regression analyses showed that the multivariate-adjusted odds ratio (OR) and 95% confidence interval (CI) for MetS was 1.13 (1.08-1.18) for each 10-b.p.m. increment of RHR (P < 0.0001). Furthermore, RHR was strongly associated with the prevalence of hypertension, high blood glucose, and dyslipidemia, but not with central obesity. A stronger association of RHR with MetS was observed among individuals aged <65 years, male, with a body mass index <24 kg/m2 , without diabetes, hypertension, abnormal lipids, and insulin resistance than among their counterparts (P < 0.05 for all). A significantly higher 10-year risk for ASCVD was observed with each 10-b.p.m. increment in RHR in both men and women (ORs [95% CIs] 1.20 [1.07-1.33] and 1.28 [1.17-1.39], respectively; Ptrend = 0.002 and < 0.0001, respectively). CONCLUSIONS: In this study, RHR was associated with a higher prevalence of MetS and elevated 10-year predicted risk of ASCVD in both Chinese men and women. Whether RHR may serve as an indicator for MetS among relatively healthy individuals requires further investigation.

5.
Cell Biol Toxicol ; 35(5): 445-456, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30941654

RESUMO

Enhancer of zeste homolog 2 (EZH2) is frequently overexpressed in breast cancer and plays an important role in maintaining the cell proliferative capacity. However, the mechanisms underlying the transcriptional regulation of EZH2 in estrogen receptor (ER)-positive breast cancer cells remain unclear. The antitumor effects of resveratrol have been reported. However, whether EZH2 was involved in these effects needs further exploration. Here, we showed that EZH2 is required for estrogen-induced cell proliferation in ER-positive breast cancer. Exposure to 17ß-estradiol (E2) upregulated EZH2 via ERα signaling, and this effect was blocked by U0126, a MEK inhibiter. Resveratrol inhibited the proliferation and colony formation in ER-positive breast cancer cells and downregulated EZH2 through inhibition of phospho-ERK1/2. These findings indicated that ERK1/2 and ER signaling-mediated EZH2 upregulation is crucial for the proliferation of ER-positive breast cancer cells. The suppression of EZH2 expression by ERK1/2 dephosphorylation is important for the antiproliferative activities of resveratrol against ER-positive breast cancer cells.

6.
J Clin Invest ; 129(6): 2318-2332, 2019 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-30896450

RESUMO

Mice selectively expressing PPARγ dominant negative mutation in vascular smooth muscle exhibit RhoBTB1-deficiency and hypertension. Our rationale was to employ genetic complementation to uncover the mechanism of action of RhoBTB1 in vascular smooth muscle. Inducible smooth muscle-specific restoration of RhoBTB1 fully corrected the hypertension and arterial stiffness by improving vasodilator function. Notably, the cardiovascular protection occurred despite preservation of increased agonist-mediated contraction and RhoA/Rho kinase activity, suggesting RhoBTB1 selectively controls vasodilation. RhoBTB1 augmented the cGMP response to nitric oxide by restraining the activity of phosphodiesterase 5 (PDE5) by acting as a substrate adaptor delivering PDE5 to the Cullin-3 E3 Ring ubiquitin ligase complex for ubiquitination inhibiting PDE5. Angiotensin-II infusion also caused RhoBTB1-deficiency and hypertension which was prevented by smooth muscle specific RhoBTB1 restoration. We conclude that RhoBTB1 protected from hypertension, vascular smooth muscle dysfunction, and arterial stiffness in at least two models of hypertension.

7.
Biomaterials ; 206: 25-40, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30925286

RESUMO

Exploiting Toll-like receptor (TLR) agonists or their certain combinations can enhance the immune potency of subunit vaccine. Nevertheless, the design of co-delivery systems which can act in a synergistic and spatio-temporal way to achieve effective and durable specific immune response is still challenging. Here we fabricated mannose-functionalized lipid-hybrid polymersomes (MAN-IMO-PS) for co-delivery of ovalbumin antigen both inside the inner core and outside the lipid layer, TLR7/8 agonist imiquimod within the hydrophobic membrane, TLR4 agonist monophosphoryl lipid A in the lipid layer as programmed nanovaccine to synergistically activate immune responses for improving vaccine efficacy. After efficiently internalized by dendritic cells via mannose targeting and TLR4 ligating, MAN-IMO-PS significantly enhanced cross-presentation and cytokine production. In addition, MAN-IMO-PS showed depot effect at the injection site and enhanced migration to draining lymph nodes. Mice immunized with MAN-IMO-PS elicited greater lymphocyte activation, CD4+ and CD8+ T cell response, effector cytokines secretion, and induced Th-1 biased humoral responses. More importantly, prophylactic vaccination by MAN-IMO-PS significantly delayed tumor occurrence, suppressed tumor growth with prolonged survival, and achieved long-term immune effect. The present study demonstrates a rationally designed nanovaccine for combining antigen, different TLR agonists, and targeting moiety in a programmed manner to induce synergistic antitumor immune response.

8.
Medicine (Baltimore) ; 98(6): e14166, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30732132

RESUMO

BACKGROUND: A meta-analysis was applied to evaluate the associations between the glutathione-S-transferases (GSTs) M1/T1 gene polymorphisms and male infertility in Chinese populations. METHODS: A comprehensive search for articles was conducted from PubMed, Web of Science, Embase, China biology medical literature database (CBM), China National Knowledge Infrastructure (CNKI), VIP, and Chinese literature database(Wang fang) up to April 30, 2018. All of the statistical analyses were performed using Review Manager 5.3 and Stata 14.0. RESULTS: Ten studies on GSTM1 gene polymorphism involving 3302 cases and 1959 controls, and ten studies on GSTT1 gene polymorphism involving 3048 cases and 1861 controls were included in this meta-analysis. Overall, the null genotype of GSTM1/GSTT1 was significantly related to male infertility risk in Chinese populations (GSTM1, OR = 1.35, 95% CI: 1.02-1.78; GSTT1, OR = 1.40, 95% CI: 1.15-1.70). In subgroup analyses stratified by infertility type, significant association was observed between GSTT1 null genotype and male infertility in both nonobstructive azoospermia (NOA) and oligoasthenozoospermia (OAT). However, the GSTM1 null genotype was associated with OAT, but not NOA in Chinese populations. The sensitivity analysis confirmed the reliability and stability of the meta-analysis. CONCLUSION: Our meta-analysis supports that the GSTM1/GSTT1 null genotype might contribute to individual susceptibility to male infertility in Chinese populations.


Assuntos
Glutationa Transferase/genética , Infertilidade Masculina/genética , Grupo com Ancestrais do Continente Asiático/genética , Azoospermia/genética , Estudos de Casos e Controles , China/epidemiologia , Predisposição Genética para Doença , Genótipo , Humanos , Infertilidade Masculina/etnologia , Masculino , Razão de Chances , Oligospermia/genética , Polimorfismo Genético , Reprodutibilidade dos Testes
9.
Artif Cells Nanomed Biotechnol ; 47(1): 512-523, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30810403

RESUMO

In recent times, Gold nanoparticles (AuNPs) synthesized from plant extracts and their anticancer activity have attracted significant attention. We report the green approach for the synthesis of AuNPs using extract from Abies spectabilis plant. In this study, the reaction parameters were optimized to control the size of the nanoparticle, which was confirmed by Transmission Electron microscopy (TEM). Various characterization technique such as SAED pattern, UV visible spectroscopy, EDX, FTIR, and AFM were employed to analyze the synthesized AuNPs obtained from A. spectabilis plant extract. Furthermore, we investigated the anticancer activities using T24 cell lines. Interestingly, the results of extensive screening on the applications of newly synthesized AuNPs were tested for their cytotoxicity effects on anticancer activity against T24 cells by MTT assay. The cell apoptosis was studied using TUNEL, DAPI, caspase activity, cell invasion and migration. Nanoparticles at different concentrations ranging from 1 to 25 µg/ml exhibited a dose dependent cytotoxicity for 24 h. Condensation and DNA fragmentation are characteristic of apoptosis by DAPI, TUNEL staining, and the significant up regulations of Beclin-1, Bax and caspase 3, whereas the expressions of anti-apoptotic Bcl-2 and Bid were down regulated. However, this study, therefore attempts to report the synthesis, characterization, and anticancer activity of gold nanoparticles of A. spectabilis plant extract beneficial for cancer therapeutics.


Assuntos
Abies/química , Antineoplásicos , Ouro , Nanopartículas Metálicas , Extratos Vegetais/química , Neoplasias da Bexiga Urinária , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Ouro/química , Ouro/farmacologia , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
10.
Carbohydr Polym ; 207: 288-296, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30600011

RESUMO

The sodium l-glutamate is reported as an efficient catalyst for the cross-linking between 1,2,3,4-butanetetracarboxylic acid (BTCA) and cellulose. Results presented ester absorbance of the treated fabrics strongly increased in the presence of the homemade l-glutamate salt, a mixture of l-glutamic acid (LGA) and NaOH at a specific ratio. Importantly, anti-wrinkle properties of the treated fabrics were significantly improved. Based on the relative concentration calculation, l-glutamate promoted the reaction of BTCA with cellulose by accelerating the formation of BTCA anhydrides and the esterification of anhydrides with cellulose. Besides, the improved anti-wrinkle property was partially attributed to the fact that the generated LGA reacted with cellulose and formed ionic cross-linking networks through amino groups with carboxyl groups in BTCA, which was confirmed by the Fourier transform infrared spectra and the computational calculations. Through detailed comparisons, l-glutamate catalyzed fabrics showed as good durability as sodium hypophosphite, indicating a possible alternative for phosphorus-containing catalysts.

11.
Int J Cancer ; 144(2): 281-289, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-29752822

RESUMO

Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next-generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non-BRCA1/2 gene. Major mutant non-BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non-BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER-2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non-BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non-BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Mutação em Linhagem Germinativa , Humanos , Pessoa de Meia-Idade
12.
Chin J Nat Med ; 16(11): 838-845, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30502765

RESUMO

Postmenopausal women, who have reduced circulating estrogen levels, are more prone to develop obesity and related metabolic diseases than premenopausal women. The absence of safe and effective treatments for postmenopausal obesity has changed the focus to natural products as alternative remedies. Total salvianolic acids (TSA) are the major water-soluble ingredients of Danshen. Salvianolic acid (SA) is the major constituent of the TSA. Salvianolic acids, including TSA and SA, are widely used in traditional Chinese medicine. In the present study, ovariectomized rats and LO2 cells were used to study the effects of salvianolic acids on body weight gain and hepatic steatosis. Salvianolic acids reduced ovariectomy (OVX)-induced body weight gain, attenuated the expressions of hepatic lipogenic genes, such as sterol regulatory element binding protein (SREBP)1, fatty acid synthase (FAS), and stearoyl-CoA desaturase (SCD)1, and decreased the liver triglyceride (TG) and total cholesterol (TC). For the molecular mechanisms, OVX and high glucose-induced phosphorylation of signal transducer and activator of transcription (STAT)-3 was inhibited by salvianolic acids treatment. In LO2 cells, inhibition of STAT-3 by siRNA attenuated the increased expression of SREBP1 and TG induced by high glucose. Salvianolic acids reduced the upregulation of SREBP1 and TG induced by high glucose in LO2 cells. In conclusion, these findings illustrated that salvianolic acids markedly alleviated the lipid metabolism disorders and protected against the postmenopausal obesity. The underlying mechanism was probably associated with the regulation of STAT-3 signaling.

13.
Cancer Immunol Res ; 2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30514794

RESUMO

Complement aids in the construction of an immunosuppressive tumor microenvironment (TME). Tumor cell-derived C3 has been previously reported, but whether and how it acts on antitumor immunity remains to be elucidated. Here, we describe a mechanism for tumor cell-derived C3 in suppressing antitumor immunity. Tumor cell-derived C3 was activated intracellularly, which results in generation of C3a. C3a modulated tumor-associated macrophages (TAMs) via C3a-C3aR-PI3Kγ signaling, thereby repressing antitumor immunity. Deletion of C3 in tumor cells that had high C3 expression enhanced efficacy of anti-PD-L1 treatment. Collectively, our results suggest tumor cell derived C3 may be a useful target for cancer immunotherapy and that targeting C3 in tumor cells may enhance antitumor immunity.

14.
Hypertension ; 72(5): 1227-1235, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30354810

RESUMO

Low-salt diet is beneficial in salt-sensitive hypertension but may provoke cardiovascular risk in patients with heart failure, diabetes mellitus, or other cardiovascular abnormalities because of endogenous renin-angiotensin system activation. PPAR (peroxisome proliferator-activated receptor)-γ is a transcription factor which promotes an antioxidant pathway in the endothelium. We studied transgenic mice expressing a dominant-negative mutation in PPAR-γ selectively in the endothelium (E-V290M) to test the hypothesis that endothelial PPAR-γ plays a protective role in response to low salt-mediated renin-angiotensin system activation. Plasma renin and Ang II (angiotensin II) were significantly and equally increased in all mice fed low salt for 6 weeks. Vasorelaxation to acetylcholine was not affected in basilar artery from E-V290M at baseline but was significantly and selectively impaired in E-V290M after low salt. Unlike basilar artery, low salt was not sufficient to induce vascular dysfunction in carotid artery or aorta. Endothelial dysfunction in the basilar artery from E-V290M mice fed low salt was attenuated by scavengers of superoxide, inhibitors of NADPH oxidase, or blockade of the Ang II AT1 (angiotensin type-1) receptor. Simultaneous AT1 and AT2 receptor blockade revealed that the restoration of endothelial function after AT1 receptor blockade was not a consequence of AT2 receptor activation. We conclude that interference with PPAR-γ in the endothelium produces endothelial dysfunction in the cerebral circulation in response to low salt-mediated activation of the endogenous renin-angiotensin system, mediated at least in part, through AT1 receptor activation and perturbed redox homeostasis. Moreover, our data suggest that the cerebral circulation may be particularly sensitive to inhibition of PPAR-γ activity and renin-angiotensin system activation.

15.
J Biomed Nanotechnol ; 14(12): 2018-2030, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30305210

RESUMO

We have developed redox-sensitive folic acid-conjugated PCL-PEG-PCL (PCEP) nanoparticles for co-delivering chemotherapeutic agent doxorubicin (DOX) and imaging and hyperthermia agent indocyanine green (ICG) with simultaneous imaging and combined therapy for breast cancer. DOX and ICG were entrapped into PCEP nanoparticles through the thin-film hydration and ultrasonic dispersion. Then nanoparticles were surface decorated with folic acid ligands against FR overexpressing breast cancers. Drug-loading nanoparticles exhibited an enhanced reduction-sensitivity in the presence of 10 mM glutathione. Nanoparticle-mediated treatment had synergistic cytotoxicity against mammary cancer cells. The conjugation of folic acid improved the uptake of nanoparticles in EMT-6 breast cancer overexpressing cell lines, and the uptake efficacy of DOX was remarkably increased by the laser irradiation. Furthermore, ex vivo fluorescence imaging confirmed that folate conjugation also improved drug accumulation in tumor. Our unique FA-DINPs system has potential for combination of chemotherapy and photothermal therapy for breast cancer.

16.
Nat Med ; 24(10): 1536-1544, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30297899

RESUMO

Impaired immunity in patients with late-stage cancer is not limited to antitumor responses, as demonstrated by poor vaccination protection and high susceptibility to infection1-3. This has been largely attributed to chemotherapy-induced impairment of innate immunity, such as neutropenia2, whereas systemic effects of tumors on hematopoiesis and adoptive immunity remain incompletely understood. Here we observed anemia associated with severe deficiency of CD8+ T cell responses against pathogens in treatment-naive mice bearing large tumors. Specifically, we identify CD45+ erythroid progenitor cells (CD71+TER119+; EPCs) as robust immunosuppressors. CD45+ EPCs, induced by tumor growth-associated extramedullary hematopoiesis, accumulate in the spleen to become a major population, outnumbering regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). The CD45+ EPC transcriptome closely resembles that of MDSCs, and, like MDSCs, reactive oxygen species production is a major mechanism underlying CD45+ EPC-mediated immunosuppression. Similarly, an immunosuppressive CD45+ EPC population was detected in patients with cancer who have anemia. These findings identify a major population of immunosuppressive cells that likely contributes to the impaired T cell responses commonly observed in patients with advanced cancer.

17.
Cancer Biol Ther ; : 1-4, 2018 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-30257133

RESUMO

BACKGROUND: In Chinese women, breast and colorectal cancers are highly prevalent. In the early stage, the primary treatment for these cancers is surgical resection. However, many patients develop a metastatic recurrence. Thus, tools that help estimate the risk of recurrence are critical. Although synchronous breast and rectal cancer is uncommon, estimating recurrence risk is even more challenging in patients with two histologically distinct malignancies. METHODS: Next generation sequencing (NGS) allows the comprehensive detection of simultaneous genome abnormalities. NGS-based circulating tumor DNA (ctDNA) profiling is a new molecular technique that has demonstrated great potential in the detection and differential diagnosis of cancer relapse. RESULTS: We present a 43-year-old female patient with synchronous breast and rectal cancer that was surgically removed 2 years prior. During regular follow-up, elevated carcinoembryonic antigen (CEA) levels were detected. ctDNA profiling revealed multiple somatic mutations that were identical to those found in rectal cancer samples. Thus, we suspected relapse of rectal cancer. Positron emission tomography-computed tomography (PET-CT) and pathogenic analysis confirmed lung metastasis of rectal cancer. CONCLUSIONS: This case demonstrated the utility of ctDNA profiling in the detection and differential diagnosis of cancer relapse in a patient with synchronous breast and rectal cancer.

18.
Exp Cell Res ; 372(1): 61-72, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30236513

RESUMO

Thioredoxin 2 (Trx2), as a member of the thioredoxin system in mitochondria, is involved in controlling mitochondrial redox state. However, the role of Trx2 in cardiac biology is not fully understood. In the present study, the expression of Trx2 is silenced in quiescent neonatal rat ventricular cardiomyocytes (NRVCs) and mitochondrial respiratory function and cardiomyocyte hypertrophy are assessed. The results show that Trx2 depletion does not induce significant cytotoxicity in quiescent NRVCs. Remarkably, Trx2 depletion results in cardiomyocyte hypertrophy as determined by increased cell size and protein synthesis. Furthermore, Trx2 depletion inhibits AMPK activity and AMPK activator reversed cellular hypertrophy. Trx2 depletion enhances mitochondrial ROS generation without impact on cellular ROS level. Trx2 depletion has no effect on mitochondrial biogenesis. Specifically, Trx2 depletion increases mitochondrial respiration flux and total ATP concentration under quiescent conditions. To decipher the relationship between ROS generation, mitochondrial respiration flux, and AMPK signaling, mitochondrial metabolism and ROS was specifically inhibited, and the results show that AMPK inactivation and hypertrophic response in Trx2-silenced cells is reversed by respiration blockers but not ROS scavenger. In conclusion, these results show that beyond mitochondrial ROS scavenging, Trx2 controls mitochondrial respiratory function in quiescent cardiomyocytes and is implicated in cardiomyocyte hypertrophy via AMPK signaling.

19.
Oncol Lett ; 16(4): 5013-5019, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30250567

RESUMO

T cells serve an important role in the destruction of tumor cells and clearing of foreign pathogens. Previous studies have suggested that the T cell immune response of tumor-bearing patients is significantly lower than that of healthy people, and the principal reason for this is lymphocytopenia, which is caused by repeated cycles of chemotherapy. In addition to lymphocytopenia, the present study revealed that cytotoxic chemotherapy also weakens the homing ability of T cells to the T-cell zone of the spleen, which decreases the possibility of encounters between antigen-specific T cells and dendritic cells presenting the appropriate antigen, thereby weakening the immune response of T cells. These changes are attributed to the lower expression of C-C motif chemokine ligand 21 (CCL21) and C-C motif chemokine ligand 19 (CCL19) in the spleen of secondary lymphoid organs (SLOs). Finally, the present study identified that chemotherapy affects the function and survival of fibroblastic reticular cells in SLOs, which are the main source of CCL21 and CCL19. These observations aid us in further understanding the mechanism that is responsible for the decreased T cell immune response following repeated cycles of chemotherapy.

20.
J Nutr Biochem ; 61: 17-23, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30179725

RESUMO

Postmenopausal women have a decline in circulating estrogen levels and are more prone to obesity and its related metabolic diseases than premenopausal women are. The absence of safe and effective conventional treatments for postmenopausal obesity has changed the focus to natural products as alternative remedies. Here, ovariectomized rats and LO2 cells were used to study the molecular basis of the effect of dietary phytoestrogens on body weight gain and hepatic steatosis. Dietary phytoestrogens can inhibit ovariectomy (OVX)-induced body weight gain, blood glucose concentration, expression of hepatic lipogenic genes, such as sterol regulatory element binding protein (SREBP)1, acetyl-CoA carboxylase (ACC)1, fatty acid synthase (FAS), and stearoyl-CoA desaturase (SCD)1, and decrease liver triglyceride (TG) content, but later estradiol withdrawal increased expression of SREBP1. Histological analysis of liver showed that dietary phytoestrogens improved OVX-induced morphological abnormalities. OVX and high glucose-induced phosphorylation of signal transducer and activator of transcription (STAT)-3 were inhibited by phytoestrogens treatment. In LO2 cells, inhibition of STAT-3 by siRNA attenuated the increased TG content and expression of SREBP1 induced by high glucose. Phytoestrogens reduced the upregulation of SREBP1 and TG induced by high glucose in LO2 cells. In conclusion, these findings illustrated that dietary phytoestrogens markedly alleviated the derangement of lipid metabolism. The underlying mechanism is probably associated with regulating STAT-3/SREBP1 signaling.

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