Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 32
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Biomed Res Int ; 2020: 2408063, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32025517

RESUMO

Postpartum depression is a disabling mental disorder commonly seen in parturients under trial of labor after cesarean, which causes serious harm to the parturients. The etiology is unclear. We hypothesized that epidural labor analgesia can reduce the incidence rate of postpartum depression. Enrolled multiparas were divided into the epidural labor analgesia group (n = 263) or nonanalgesia group (n = 160) according to their own request. Edinburgh Postnatal Depression Scale was used to assess their mental status at 48 hours and 42 days after delivery. Relative perinatal variables were collected and further analyzed using univariate analysis and multivariate logistic regression analysis to assess the relation of epidural analgesia with the occurrence of postpartum depression under trial of labor after cesarean. The Edinburgh Postnatal Depression Scale score 48 hours ≥ 10 in the no epidural analgesia group was 26.42% while the epidural analgesia group was 8.49% (OR, 0.209; 95% CI, 0.096-0.429; P < 0.001). The Edinburgh Postnatal Depression Scale score 42 day ≥ 10 in the no epidural analgesia group was 25.16% while the epidural analgesia group was 6.59% (OR, 0.235; 95% CI, 0.113-0.469; P < 0.001). The incidence of postpartum depression was significantly lower in the epidural labor analgesia group at 48 hours and 42 days. There was also a significant relation between the Edinburgh Postnatal Depression Scale scores at 48 hours and 42 days after delivery. Epidural analgesia, discomfort within 42 days, and self-rating anxiety scale are independent predictors of postpartum depression for trial of labor after cesarean in 42 days. Epidural labor analgesia is associated with a decreased risk of postpartum depression. Further study with a large sample size and more centers is needed to evaluate the impact of epidural analgesia on the occurrence of postpartum depression. Chinese Clinical Trial Register, ChiCTR-ONC-17010654.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31990032

RESUMO

BACKGROUND: Both the clinical and pre-clinical studies have suggested embryonic or infant exposure to ketamine, a general anaesthetic, pose a great threat to the developing brain. However, it remains unclear about how ketamine may contribute to the brain dysfunctions. METHODS: Mouse model of prenatal exposure to ketamine was generated by intramuscular injection and continuous intraperitoneal infusion of pregnant mice. Open Field Test (OFT) and Elevated Plus Maze Test (EPM) were used to analyze the behavioral alterations induced by ketamine. Immunostaining by c-Fos was used to map the neuron activity. Chemogenetic modulation of the neurons was used to rescue the abnormal neuron activity and behaviors. RESULTS: Here we show that mice prenatally exposed to ketamine displayed anxiety-like behaviors during adulthood, but not during puberty. C-Fos immunostaining identified abnormal neuronal activity in Bed Nucleus of the Stria Terminalis (BNST). Silencing of BNST by chemogenetics restores the anxiety-like behaviors. CONCLUSIONS: Taken together, these results demonstrate a circuitry mechanism of ketamine-induced anxiety-like behaviors.

3.
BMC Pregnancy Childbirth ; 19(1): 498, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842795

RESUMO

BACKGROUND: The trial of labor after cesarean section (TOLAC) is a relatively new technique in mainland of China, and epidural analgesia is one of the risk factors for uterine rupture. This study aimed to evaluate the effect of epidural analgesia on primary labor outcome [success rate of vaginal birth after cesarean (VBAC)], parturient complications and neonatal outcomes after TOLAC in Chinese multiparas based on a strictly uniform TOLAC indication, management and epidural protocol. METHODS: A total of 423 multiparas undergoing TOLAC were enrolled in this study from January 2017 to February 2018. Multiparas were divided into two groups according to whether they received epidural analgesia (study group, N = 263) or not (control group, N = 160) during labor. Maternal delivery outcomes and neonatal characteristics were recorded and evaluated using univariate analysis, multivariable logistic regression and propensity score matching (PSM). RESULTS: The success rate of VBAC was remarkably higher (85.55% vs. 69.38%, p < 0.01) in study group. Epidural analgesia significantly shortened initiating lactation period and declined Visual Analogue Score (VAS). It also showed more superiority in neonatal umbilical arterial blood pH value. After matching by PSM, multivariable logistic regression revealed that the correction of confounding factors including epidural analgesia, cervical Bishop score at admission and spontaneous onset of labor were still shown as promotion probability in study group (OR = 4.480, 1.360, and 10.188, respectively; 95%CI = 2.025-10.660, 1.113-1.673, and 2.875-48.418, respectively; p < 0.001, p = 0.003, and p < 0.001, respectively). CONCLUSIONS: Epidural analgesia could reduce labor pain, and no increased risk of postpartum bleeding or uterine rupture, as well as adverse effects in newborns were observed. The labor duration of multiparas was increased, but within acceptable range. In summary, epidural analgesia may be safe for both mother and neonate in the three studied hospitals. TRIAL REGISTRATION: Chineses Clinical Trial Register, ChiCTR-ONC-17010654. Registered February 16th, 2017.

4.
Nat Commun ; 10(1): 4477, 2019 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578331

RESUMO

Single crystal X-ray diffraction is arguably the most definitive method for molecular structure determination, but the inability to grow suitable single crystals can frustrate conventional X-ray diffraction analysis. We report herein an approach to molecular structure determination that relies on a versatile toolkit of guanidinium organosulfonate hydrogen-bonded host frameworks that form crystalline inclusion compounds with target molecules in a single-step crystallization, complementing the crystalline sponge method that relies on diffusion of the target into the cages of a metal-organic framework. The peculiar properties of the host frameworks enable rapid stoichiometric inclusion of a wide range of target molecules with full occupancy, typically without disorder and accompanying solvent, affording well-refined structures. Moreover, anomalous scattering by the framework sulfur atoms enables reliable assignment of absolute configuration of stereogenic centers. An ever-expanding library of organosulfonates provides a toolkit of frameworks for capturing specific target molecules for their structure determination.

5.
Front Immunol ; 10: 1647, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379845

RESUMO

Background: Antibody-dependent cellular cytotoxicity (ADCC), which mainly mediated by natural killer (NK) cells, may play a critical role in human immunodeficiency virus type-1 (HIV-1) disease progression. However, the potential mechanisms that affecting NK-mediated ADCC response are still not well-elucidated. Methods: Antigen-antibody complex model of Ab-opsonized P815 cells was adopted to induce a typical non-specific ADCC response. The capacities of HIV-1 specific NK-ADCC were measured by using the combination model of gp120 protein and plasma of HIV-1 elite controllers. The levels of plasma cytokine were measured by ELISA. Anti-IL-2 blocking antibody was used to analyze the impact of activated CD56+ T cells on NK-ADCC response. Results: IL-2, IL-15, IFN-α, and IFN-ß could effectively enhance the non-specific and HIV-1-specific NK-ADCC responses. Compared with healthy controls, HIV-1-infected patients showed decreased plasma IL-2 levels, while no differences of plasma IFN-α, IL-15, and IFN-ß were presented. IL-2 production was detected from CD56+ T cells activated through antibody-dependent manner. The capability of NK-ADCC could be weakened by blocking IL-2 secretion from activated CD56+ T cells. Although no difference of frequencies of CD56+ T cells was found between HIV-1-infected patients and healthy controls, deficient IL-2 secretion from activated CD56+ T were found in chronic HIV-1 infection. Conclusions: The impaired ability of activated CD56+ T cells to secreting IL-2 might contribute to the attenuated NK cell-mediated ADCC function in HIV-1 infection.

7.
Int J Biol Macromol ; 132: 478-486, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30943422

RESUMO

We report an ingenious technique to prepare magnetic alkaline lignin-dopamine nanoparticles (AL-DA/Fe3O4 NPs). Alkaline lignin, a kind of abundant waste from agriculture, pulping and bio-energy industry, was functionalized by the conjugation with DA molecules and nano-precipitation method. Benefiting from the three-dimensional network of lignin and mussel-inspired DA molecules, chromium(III) can be effectively removed by physisorption and chemisorption. The maximum Cr(III) adsorption capacity of AL-DA/Fe3O4 NPs was found to be 44.56 mg/g, which was among the highest of previously reported biomass-based Cr(III) adsorbents. Moreover, sensitive magnetic responsiveness (24.6 emu/g) of AL-DA/Fe3O4 NPs can be more helpful in recycling (over 90% recycled within 2 min) and multiple reusing. The preparation of this low-cost, high adsorptive capacity and good ecofriendly lignin-based nano-adsorbent is expected to become a sustainable technology to simultaneously achieve the wastewater reutilization from pulping and bio-energy industry and purification of other modern industries.


Assuntos
Materiais Biomiméticos/química , Bivalves , Cromo/química , Cromo/isolamento & purificação , Lignina/química , Nanopartículas de Magnetita/química , Purificação da Água/métodos , Adsorção , Animais , Dopamina/química , Química Verde , Concentração de Íons de Hidrogênio , Cinética , Águas Residuárias/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação
8.
Eur J Pharmacol ; 843: 268-276, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30472200

RESUMO

The impacts of prenatal propofol on cognition and emotion of offspring remain elusive. In the present study, pregnant rats in the second trimester were anesthetized with propofol. Neuronal apoptosis and proliferation was determined in fetuses and postnatal rats by detecting caspase-3 and BrdU expression. The offspring were subjected to several behavior tests. Then the pyramidal neurons in hippocampus and the expression of NR1, NR2A, and NR2B subunits of NMDA receptor and PSD-95 in frontal cortex were examined. Propofol exposure significantly increased the number of caspase-3+ cells in lateral ganglionic eminence and hippocampus compared with control group (P < 0.001). The number of BrdU+ cells in the subventricular zone (SVZ) and dentate gyrus (DG) was also reduced in propofol group (P < 0.001). In propofol group, the swimming distance and time in the quadrant were shorter,but longer out of the quadrant. The number of escapes was less than those of the control group. Prenatal propofol exposure also decreased the sucrose preference, reduced the numbers of grooming, crossing, and rearing of the pups, and increased the fecal particle numbers and immobility time (P < 0.05). There were fewer and shorter dendritic branches of pyramidal neurons in the CA1 and CA3 of offspring. The expression of NR1, NR2A, NR2B, and PSD-95 in the frontal cortex was downregulated by propofol exposure (P < 0.001). These data suggested that prenatal propofol exposure impairs neuronal development, which may be associated with depression- and anxiety-like behaviors and cognitive disorders in offspring.


Assuntos
Anestésicos Intravenosos/farmacologia , Cognição/efeitos dos fármacos , Hipnóticos e Sedativos/farmacologia , Transtornos do Humor/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal , Propofol/farmacologia , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Regulação para Baixo , Feminino , Troca Materno-Fetal , Gravidez , Ratos Sprague-Dawley
9.
Exp Ther Med ; 16(6): 4831-4835, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30542438

RESUMO

Propofol is the most common intravenous anesthetic agent used in clinical practice. Propofol can induce insulin resistance in mouse primary hepatocytes, however the molecular mechanism through which propofol acts remains largely unknown. Based on previous studies, it was hypothesized that phosphatase and tensin homolog (PTEN) is involved in propofol-mediated insulin resistance. The aim of the present study was to investigate the biological function of PTEN and its molecular mechanism in propofol-induced insulin resistance in mouse primary hepatocytes. Mouse primary hepatocytes were treated with propofol and transfected with small interfering RNA (siRNA)-996 to silence the endogenous expression of PTEN. The current study assessed the effects of propofol and PTEN knockdown on the expression of PTEN and several key enzymes of the phosphoinositide 3-kinase/protein kinase B/glycogen synthase kinase-3ß signaling pathway, as well as the glycogen content in mouse primary hepatocytes. Treatment with propofol significantly increased protein and mRNA PTEN expression in mouse primary hepatocytes. In addition, knockdown of PTEN reversed propofol-induced insulin resistance in mouse primary hepatocytes. The present study indicated that PTEN serves a role in the physiological process of propofol-induced insulin resistance in mouse primary hepatocytes, and PTEN inhibition may be a potential target for therapeutic intervention against propofol-induced adverse effects.

10.
Sci Rep ; 8(1): 17497, 2018 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-30504858

RESUMO

Either HIV or HCV monoinfection could result in an abnormal status of platelets. As two key indicators reflecting activation and function of platelets, the changes of platelet counts and mean platelet volume (MPV) in HIV/HCV-coinfected patients have not been clearly identified. In the present study, a total of 318 former plasma donors were investigated in 2006, and 66% (201 individuals) of primary recruiters were followed up in 2014. By horizontal comparison in 2006, the decrease of platelet counts in HIV/HCV coinfection was greater than that in HIV or HCV monoinfection. MPV scores were lower in HIV monoinfection compared with healthy controls, while no difference was found in HIV/HCV coinfection. Platelet counts were shown to be negatively correlated with MPV scores in total recruited population (r = 0.432, P < 0.001). Interestingly, by comparison of data from two time points of 2006 and 2014, significant decrease of platelets (P = 0.004) and increase of MPV (P = 0.004) were found only in HCV monoinfected patients, which may associate with slow progression of hepatic fibrosis induced by chronic HCV infection. Nonetheless, no significant changes of platelet counts and MPV were found from 2006 to 2014 in coinfected patients. In conclusion, HCV coinfection aggravated the decrease of platelet counts, but not MPV score in chronic HIV infection. MPV showed poor applicability in reflecting the status of platelets in HIV/HCV-coinfected patients.


Assuntos
Infecções por HIV/sangue , Hepatite C/complicações , Contagem de Plaquetas , Infecções por HIV/complicações , Humanos , Volume Plaquetário Médio
11.
European J Org Chem ; 2018(32): 4381-4388, 2018 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-30220876

RESUMO

The Rh(III)-catalyzed synthesis of 4-substituted isoquinolones and 2-pyridones by the annulation of N-methoxyamides and nitroalkenes has been developed. Both aliphatic and aromatic nitroalkenes were effective inputs. Annulations also proceeded for aromatic, alkenyl, and heteroaromatic C-H bond starting materials. Moreover, benzoic acid provided a novel nitrodihydroisocoumarin. The structure and relative stereochemistry of this compound, which is an oil at room temperature, was determined unambiguously by single crystal X-ray diffraction of its inclusion complex with a hydrogen-bonded host framework.

12.
J Am Chem Soc ; 140(40): 12915-12921, 2018 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-30264567

RESUMO

A new inclusion compound consisting of a guanidinium 1,3,5-tri(4-sulfophenyl)benzene (G3TSPHB) host framework containing isophorone guests that surround isolated and seemingly inaccessible pockets was amenable to guest exchange with hexafluorobenzene (HFB) through a single crystal-single crystal transformation (SCSCT). Single-crystal X-ray diffraction of intermediate transformation states, from the parent compound G3TSPHB·(isophorone)3.7·(methanol)5.4 to the final state G3TSPHB·(isophorone)3.1·(HFB)2·(methanol)2, indicated a crystal symmetry change from monoclinic to hexagonal prior to full incorporation of HFB. Optical microscopy during the SCSCT revealed the formation of lamellae, which expanded and then coalesced into a single crystal when the phase transformation was complete. In situ Raman microscopy revealed changes in the orientation of isophorone guests during the transformation that suggested a pathway for HFB entry into the host cavities. The SCSCT occurs more rapidly than expected on the basis of simple diffusion, consistent with facilitated transport along the lamellae interfaces and a reduction in the length scale for guest exchange.

13.
Neuropsychiatr Dis Treat ; 14: 2191-2206, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30214209

RESUMO

Background: Propofol induces short- and long-term neurotoxicity. Our previous study showed that dexmedetomidine (Dex) can attenuate the propofol-induced acute neurotoxicity in rodents by enhancing the PI3K/Akt signaling. However, whether treatment of young rats with Dex could protect them from long-term neurotoxicity induced by propofol is unclear. Materials and methods: Seven-day-old male Sprague Dawley rats were randomized and injected intraperitoneally with saline (100 µL, NS), propofol (100 mg/kg), Dex (75 µg/kg), propofol (100 mg/kg) plus Dex (25, 50 or 75 µg/kg), 10% dimethyl sulfoxide (DMSO, 100 µL) or TDZD-8 (a GSK3ß inhibitor, 1 mg/kg), or intracerebroventricularly with DMSO (5 µL) or LY294002 (a PI3K inhibitor, 25 µg/5 µL DMSO). Other rats in the experimental group were injected with the same doses of propofol, Dex and LY294002 or TDZD-8. All the rats were monitored until they were 9 weeks old. Their spatial learning and memory were tested by Morris water maze. The neuronal apoptosis, expression of PSD95, expression and phosphorylation of Akt and GSK3ß and synaptic ultrastructures were determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, immunohistochemistry, Western blot and transmission electron microscopy assays, respectively. Results: Compared with the NS control group, young rats injected with intralipid, Dex, TDZD-8, LY294002 or DMSO alone did not show any significant change as they aged. Propofol significantly increased the escape latency time, hippocampal neuroapoptosis and synaptic ultrastructural changes but decreased the relative levels of PSD95 expression, and Akt and GSK3ß phosphorylation in the developing hippocampus of the rats. The neuronal toxic effects of propofol were significantly mitigated by the pretreatment with a higher dose of Dex. The neuroprotective effect of Dex was enhanced by the treatment with TDZD-8, but was completely abrogated by the treatment with LY294002. Conclusion: Our results indicated that the pretreatment of young rats with Dex attenuated the propofol-induced long-term neurotoxicity in their developing hippocampus by enhancing the PI3K/Akt signaling.

14.
Clin Exp Pharmacol Physiol ; 45(10): 1002-1009, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29905955

RESUMO

Regulatory T (Treg) cells are critical suppressors of inflammation and are thought to exert mainly deleterious effects in cancers. In colorectal cancer (CRC), Foxp3+ Treg accumulation in tumors was associated with poor prognosis. Hence, we examined the circulating Treg cells in CRC patients. Compared to controls, CRC patients presented mild upregulations in CD4+ CD25+/hi T cells and in the more canonical CD4+ CD25+/hi Foxp3+ Treg cells in peripheral blood mononuclear cells. Both of these Treg populations could be roughly divided into lymphocyte activation gene 3 negative T cell immunoglobulin and mucin-domain containing-3 negative (LAG3- TIM3- ) and LAG3+ TIM3+ subsets. In CRC patients, the LAG3+ TIM3+ subset represented approximately half of CD4+ CD25+/hi T cells and greater than 60% of CD4+ CD25+/hi Foxp3+ Treg cells, which was significantly more frequent than in healthy controls. Compared to the LAG3- TIM3- CD4+ CD25+/hi T cells, the LAG3+ TIM3+ CD4+ CD25+/hi T cells presented considerably higher transforming growth factor-ß and slightly higher interleukin (IL)-10 secretion, together with higher cytotoxic T-lymphocyte associated protein 4 and Foxp3 expression levels. Notably, macrophages following incubation with LAG3- TIM3- CD4+ CD25+/hi T cells and LAG3+ TIM3+ CD4+ CD25+/hi T cells displayed different characteristics. Macrophages incubated with LAG3+ TIM3+ CD4+ CD25+/hi T cells presented lower expression of major histocompatibility complex class II, CD80, CD86, and tumor necrosis factor-α but higher expression of IL-10, than macrophages incubated with LAG3- TIM3- CD4+ CD25+/hi T cells. Together, our investigations demonstrated that CRC patients presented an enrichment of circulating Treg cells, in which the LAG3+ TIM3+ subset exhibited more potent expression of inhibitory molecules, and furthermore, the LAG3+ TIM3+ Treg cells could suppress the proinflammatory activation of macrophages more potently than the LAG3- TIM3- Treg cells.


Assuntos
Antígenos CD/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Regulação Neoplásica da Expressão Gênica , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Macrófagos/imunologia , Linfócitos T Reguladores/citologia , Adulto , Idoso , Estudos de Casos e Controles , Proliferação de Células , Feminino , Humanos , Interleucina-10/metabolismo , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade
15.
Biomed Res Int ; 2018: 2708175, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29951531

RESUMO

The aim of this paper is to evaluate the efficacy and safety of three different norepinephrine dosing regimens for preventing spinal hypotension in cesarean section. In this randomized double-blinded controlled study, 120 parturients scheduled for elective section delivery under spinal anesthesia were assigned to 1 of 4 groups. In the control group, patients received saline infusion. In three norepinephrine groups, the infusion dosage regimens were 5, 10, and 15 µg/kg/h, respectively. Hypotension was treated with a rescue bolus of 10 µg norepinephrine. The study protocol was continued until the end of surgery. The primary outcome was the proportion of participants that underwent hypotension. The proportion of hypotension participants was significantly reduced in the norepinephrine groups (37.9%, 20%, and 25%, respectively) compared to that in the control group (86.7%). However, the highest dose of norepinephrine (15 µg/kg/h) resulted in more hypertension episodes. In addition, blood pressure was better maintained in the norepinephrine 5 µg/kg/h and 10 µg/kg/h groups than in the control group and 15 µg/kg/h group. No significant differences in other hemodynamic variables, adverse effects, maternal and neonatal blood gases, or Apgar scores were observed among the groups. In summary, for patients who undergo cesarean delivery under spinal anesthesia, infusion of 5-10 µg/kg/h norepinephrine was effective to reduce hypotension incidence without significant adverse effects on maternal and neonatal outcomes. Clinical Trial Registration Number is ChiCTR-INR-16009452.


Assuntos
Raquianestesia , Cesárea , Hipotensão/prevenção & controle , Norepinefrina/uso terapêutico , Adulto , Anestesia Obstétrica , Método Duplo-Cego , Feminino , Humanos , Fenilefrina , Gravidez
16.
BMC Infect Dis ; 18(1): 254, 2018 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-29866105

RESUMO

BACKGROUND: Female gender and favorable IFNL3 genotypes are the primary independent predictors of spontaneous clearance of HCV infection. However, chronic hepatitis C infection occurs in numerous women carrying favorable IFNL3 genotypes, indicating that other host and/or virological factors contribute to the prognosis of infection. METHODS: A cohort of 137 anti-HCV-positive female Han Chinese cases, including 64 chronic HCV carriers and 73 HCV spontaneous resolvers, was recruited in the study. 111 SNPs in 23 genes encoding HCV co-receptors, transcription factors, Toll-like receptors, co-stimulating molecules, and cytokines were selected for SNP analysis. RESULTS: After comparison of genotypes and allelotype frequencies of 111 SNPs in 23 genes in the primary cohort, the SNPs rs9826 (P = 0.024 for CC/TT/CT; P = 0.015 for C allele/T allele) and rs1521177 (P = 0.017 for GG/TT/GT; P = 0.006 for G allele/T allele) in the RORC gene were significantly associated with spontaneous HCV clearance. In the sub-cohort carrying favorable IFNL3 genotypes (rs12979860CC, rs8099917 TT, rs12980275 AA), rs1521177 (genotype: P = 0.040; allelotype: P = 0.021) remained significantly associated with spontaneous HCV clearance. Importantly, the most common RORC haplotype rs9826-T/rs1521177-T was presented at significantly different frequencies in resolvers and carriers in both the primary cohort (P = 0.0027) and the IFNL3 favorable sub-cohort (P = 0.0117). CONCLUSIONS: This study indicates that genetic polymorphisms in human Th17-related RORC gene are associated with different natural prognosis of HCV infection. The RORC haplotype, rs9826-T/rs1521177-T, was favorable for spontaneous clearance of HCV infection.


Assuntos
Hepatite C Crônica/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Polimorfismo de Nucleotídeo Único , Células Th17/fisiologia , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Genótipo , Haplótipos , Humanos , Interferons , Interleucinas/genética , Pessoa de Meia-Idade , Remissão Espontânea , Células Th17/virologia
17.
FEBS Lett ; 592(4): 599-609, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29364502

RESUMO

Although colorectal cancer (CRC) is a prevalent malignancy of the digestive system, the underlying mechanisms of CRC tumorigenesis are still elusive. Arrestin-related domain-containing protein-3 (ARRDC3) has been reported to promote lysosome-mediated protein degradation. In the present study, we find that the expression of ARRDC3 is downregulated in CRC specimens. Mechanistically, we reveal that ARRDC3 binds and decreases expression of the oncoprotein YAP, the cotranscription factor of the Hippo pathway. The regulation of the Hippo pathway by ARRDC3 is conserved from Drosophila to mammals. Furthermore, we demonstrate that ARRDC3 plays an anti-oncogenic role in CRC progression by promoting YAP degradation. Finally, we show that ARRDC3 increases the sensitivity of CRC cells toward chemotherapeutic drugs. Taken together, our findings point to ARRDC3 as a potential target for CRC treatment.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Arrestinas/metabolismo , Neoplasias Colorretais/patologia , Progressão da Doença , Fosfoproteínas/metabolismo , Animais , Carcinogênese , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/metabolismo , Regulação para Baixo , Humanos , Metástase Neoplásica , Estabilidade Proteica , Proteólise , Fatores de Transcrição
18.
Mediators Inflamm ; 2018: 6158671, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30670927

RESUMO

Background: Inflammatory responses induced by intestinal ischemia-reperfusion (IIR) lead to serious systemic organ dysfunction and pose a challenge for current treatment. This study aimed at investigating the effects of resveratrol on IIR-induced intestinal injury and its influence on mast cells (MCs) in rats. Methods: Rats subjected to intestinal ischemia for 60 min and 4 h of IIR were investigated. Animals were randomly divided into five groups (n = 8 per group): sham, IIR, resveratrol (RESV, 15 mg/kg/day for 5 days before operation) + IIR, cromolyn sodium (CS, MC membrane stabilizer) + IIR, and RESV + compound 48/80 (CP, MC agonist) + IIR. Results: Intestinal injury and increased proinflammatory cytokines including tumor necrosis factor-α, interleukin-1ß, and interleukin-18 were observed in the IIR group. Intestinal MC-related tryptase and ß-hexosaminidase levels were also increased after rats were subjected to IIR accompanied by activation of NLRP3 inflammasomes. Interestingly, pretreatment with resveratrol significantly suppressed the activities of proinflammatory cytokines and attenuated intestinal injury. Resveratrol also reduced MC and NLRP3 inflammasome activation, which was consistent with the effects of cromolyn sodium. However, the protective effects of resveratrol were reversed by the MC agonist compound 48/80. Conclusions: In summary, these findings reveal that resveratrol suppressed IIR injury by stabilizing MCs, preventing them from degranulation, accompanied with intestinal mucosa NLRP3 inflammasome inhibition and intestinal epithelial cell apoptosis reduction.


Assuntos
Inflamassomos/metabolismo , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Resveratrol/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Imunofluorescência , Hexosaminidases/metabolismo , Marcação In Situ das Extremidades Cortadas , Inflamassomos/efeitos dos fármacos , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
19.
Life Sci ; 185: 30-37, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28733146

RESUMO

BACKGROUND: Intestinal ischemia/reperfusion (IIR) leads to acute lung injury (ALI) distally by aggravating pulmonary oxidative stress. Resveratrol is effective in attenuating ALI through its antioxidant capacity. This study aimed to determine the effects of resveratrol on IIR-induced ALI and to explore the role of mast cells (MCs) activation in a rat model of IIR. METHODS: Adult Sprague-Dawley rats were subjected to IIR by occluding the superior mesenteric artery for 60min followed by 4-hour reperfusion. Resveratrol was intraperitoneally injected at a dose of 15mg/kg for 5days before IIR. MCs stabilizer/inhibitor cromolyn sodium and degranulator compound 48/80 were used to explore the interaction between resveratrol and MCs. Lung tissues were collected for pathological detection and MCs staining. Pulmonary protein expression of surfactant protein-C (SP-C), tryptase, p47phox and gp91phox (two NADPH oxidase subunits), ICAM-1(intercellular adhesion molecule-1) and P-selectin were detected. The levels of oxidative stress markers (SOD, MDA, H2O2 and MPO) and ß-hexosaminidase were also measured. RESULTS: At the end of IIR, lung injury was significantly increased and was associated with decreased expression of SP-C and increased lung oxidative stress. Increased inflammation as well as activation of MCs was also observed in the lungs after IIR. All these changes were prevented or reversed by resveratrol pretreatment or MCs inhibition with cromolyn sodium. However, these protective effects of resveratrol or cromolyn sodium were reduced by MCs degranulator compound 48/80. CONCLUSIONS: These findings reveal that resveratrol attenuates IIR-induced ALI by reducing NADPH oxidase protein expression and inflammation through stabilizing MCs.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Enteropatias/tratamento farmacológico , Mastócitos/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Estilbenos/farmacologia , Lesão Pulmonar Aguda/etiologia , Animais , Antioxidantes/farmacologia , Modelos Animais de Doenças , Enteropatias/complicações , Masculino , Mastócitos/metabolismo , NADPH Oxidases/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/complicações , Resveratrol
20.
Arch Gynecol Obstet ; 295(5): 1167-1174, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28357557

RESUMO

PURPOSE: Postpartum depression is a common complication of childbirth. In the last decade, it has been suggested that subdissociative-dose ketamine is a fast-acting antidepressant. We aimed to investigate the efficacy of low-dose ketamine administered during caesarean section in preventing postpartum depression. METHODS: Using a randomized, double-blind, placebo-controlled design, 330 parturients who were scheduled to undergo caesarean section were enrolled in this trial. The parturients were randomly assigned to receive intravenous ketamine (0.25 mg/kg diluted to 10 mL with 0.9% saline) or placebo (10 mL of 0.9% saline) within 5 min following clamping of the neonatal umbilical cord. The primary outcome was the degree of depression, which was evaluated using the Edinburgh Postnatal Depression Scale (EPDS) (a threshold of 9/10 was used) at 3 days and 6 weeks after delivery. The secondary outcome was the numeric rating scale score of pain at 3 day and 6 week postpartum. RESULTS: No significant differences were found in the prevalence of postpartum depression between the two groups at 3 days and 6 weeks after delivery. The pain scores measured at 3 days postoperatively were not significantly different between the groups, whereas the scores measured at 6 week postpartum were significantly reduced in the treatment group compared with the saline group (P = 0.014). CONCLUSIONS: Intra-operative low-dose ketamine (0.25 mg/kg) does not have a preventive effect on postpartum depression.


Assuntos
Depressão Pós-Parto/prevenção & controle , Ketamina/administração & dosagem , Adulto , Cesárea , Método Duplo-Cego , Feminino , Humanos , Dor/tratamento farmacológico , Gravidez , Estudos Prospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA