Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 310
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Neurosci Lett ; 721: 134817, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32032748

RESUMO

Protein phosphatase 2A (PP2A) is an evolutionarily conserved serine/threonine phosphatase abundant in mammalian brains. Although recent research has revealed that PP2A plays important roles in cocaine and morphine addictions, the mechanism of action of PP2A in methamphetamine (METH) addiction is unclear. LB100 is a PP2A inhibitor able to penetrate the blood-brain barrier (BBB); the role of LB100 in METH-induced conditioned place preference (CPP) has not yet been reported. Here, we explored the roles of LB100 in distinct phases of METH-induced CPP. Our findings indicate that LB100 inhibits the acquisition and reinstatement of METH-induced CPP and promotes the extinction of METH-induced CPP. Moreover, LB100 alone did not affect the natural preference of mice. Intriguingly, repeated administration of LB100 in the extinction phase did not inhibit the reinstatement of METH-induced CPP, but LB100 injection prior to METH administration could significantly block it. Taken together, we found that LB100 has significant effects on different phases of METH-induced CPP, and is therefore, a potentially promising therapeutic for METH addiction.

2.
Neurology ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932513

RESUMO

OBJECTIVE: We evaluated the interaction of serum folate and vitamin B12 with methylenetetrahydrofolate reductase (MTHFR) C677T genotypes on the risk of first ischemic stroke and on the efficacy of folic acid treatment in prevention of first ischemic stroke. METHODS: A total of 20,702 hypertensive adults were randomized to a double-blind treatment of daily enalapril 10 mg and folic acid 0.8 mg or enalapril 10 mg alone. Participants were followed up every 3 months. RESULTS: Median values of folate and B12 concentrations at baseline were 8.1 ng/mL and 280.2 pmol/L, respectively. Over a median of 4.5 years, among those not receiving folic acid, participants with baseline serum B12 or serum folate above the median had a significantly lower risk of first ischemic stroke (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.57-0.96), especially in those with MTHFR 677 CC genotype (wild-type) (HR, 0.49; 95% CI, 0.31-0.78). Folic acid treatment significantly reduced the risk of first ischemic stroke in participants with both folate and B12 below the median (2.3% in enalapril-folic acid group vs 3.6% in enalapril-only group; HR, 0.62; 95% CI, 0.46-0.86), particularly in MTHFR 677 CC carriers (1.6% vs 4.9%; HR, 0.24; 95% CI, 0.11-0.55). However, TT homozygotes responded better with both folate and B12 levels above the median (HR, 0.28; 95% CI, 0.10-0.75). CONCLUSIONS: The risk of first ischemic stroke was significantly higher in hypertensive patients with low levels of both folate and B12. Effect of folic acid treatment was greatest in patients with low folate and B12 with the CC genotype, and with high folate and B12 with the TT genotype.

3.
J Clin Endocrinol Metab ; 105(3)2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31976527

RESUMO

CONTEXT: The association of the combination of body mass index (BMI) and waist circumference (WC) with the risk of proteinuria has previously not been comprehensively investigated and results have been inconclusive. OBJECTIVE: To examine BMI and WC in relation to new-onset proteinuria in Chinese hypertensive patients. DESIGN AND SETTING: Post hoc analysis of the renal substudy of the China Stroke Primary Prevention Trial (CSPPT). PATIENTS: 10 805 hypertensive patients without proteinuria at baseline. MAIN OUTCOME MEASURE: The primary outcome was new-onset proteinuria, defined as a urine dipstick protein reading ≥ 1 + at the exit visit, after a median follow-up duration of 4.4 years. RESULTS: When analyzed separately, increased BMI (≥ 28 kg/m2, quartile 4; odds ratio [OR], 1.36; 95% confidence interval [CI], 1.08-1.72), or increased WC (≥ 91cm for females, quartile 4; OR, 1.35; 95% CI, 1.01-1.80; and ≥ 79 cm for males, quartile 2-4; OR, 1.60; 95% CI, 1.03-2.50) were each significantly associated with higher risk of new-onset proteinuria. When analyzed jointly, participants without increased BMI and increased WC had the lowest risk, while those with both increased BMI and increased WC had the highest risk of proteinuria (OR, 1.61; 95% CI, 1.21-2.13). Notably, participants with only increased WC also had significantly increased risk of proteinuria (OR, 1.39; 95% CI, 1.04-1.85). CONCLUSION: In Chinese hypertensive patients, increased BMI and increased WC were individually and jointly associated with a higher risk of new-onset proteinuria, underscoring the value of monitoring both BMI and WC in assessing proteinuria risk.

4.
Gynecol Endocrinol ; : 1-3, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31899992

RESUMO

Type A insulin resistance syndrome (TAIRS) is a rare subtype of congenital insulin resistance (IR), which is characterized by specific clinical manifestations without clear diagnostic criteria and is easily misdiagnosed or overlooked. Herein we present a case of TAIRS with acanthosis nigricans (AN), severe IR, polycystic ovaries, hyperandrogenism and its consequence such as menstrual disturbances, acne and hirsutism. A heterozygous mutation, p.Arg1201Gln, in the insulin receptor (INSR) was detected. This mutation in the tyrosine kinase domain has been described before and shown to impair tyrosine kinase activity and is responsible for IR.

5.
Life Sci ; 243: 117251, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31904365

RESUMO

AIMS: Heat shock protein 27 regulates homeostasis of skeletal and cardiac muscle proteins in various stressful states including diabetes and exercise. Aerobic exercise can inhibit or ameliorate cardiac structural abnormality and dysfunction in diabetic cardiomyopathy. The aim of this study was to evaluate the role of HSP27 in aerobic exercise improving cardiac diastolic dysfunction in type 2 diabetic rats. METHODS: Forty male Sprague-Dawley rats were randomly divided into the following groups: control, control + aerobic exercise, diabetic, and diabetic + aerobic exercise. Diabetes was induced by feeding with a high-fat high-sugar diet for 7-weeks followed by a single intraperitoneal injection of streptozotocin (30 mg/kg) in male rats. Moderate aerobic exercise training was performed on a treadmill for 8 weeks after induction of diabetes. KEY FINDINGS: Aerobic exercise increased left ventricular end-diastolic internal diameter, left ventricular end-diastolic volume, myocardial HSP27 protein expression, HSP27-S82 phosphorylation levels, pHSP27-titin binding and improved cardiac muscle fibre alignment in diabetic rats. SIGNIFICANCE: Our study indicates that moderate aerobic exercise increases HSP27 activation, improves cardiomyocyte fibre alignment and restores cardiac diastolic function.

6.
Int J Pediatr Otorhinolaryngol ; 128: 109689, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31785455

RESUMO

Copy number variation is an extensively studied cause of hereditary diseases. However, its role in hereditary sensorineural deafness has been rarely reported. Using targeted sequencing, SNP array and qPCR, we found a novel 622.2 kb duplication of 6q14.1 in a patient with congenital sensorineural hearing loss and cochlear aplasia. The duplication included MYO6 and IMPG1 genes. FISH study confirmed that this duplication was inherited from the patient's mosaic mother.

7.
Gene ; 726: 144226, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31669644

RESUMO

Hereditary spherocytosis is a congenital red blood cell disorder. Typical clinical manifestations include anemia, jaundice and splenomegaly, which overlap with the thalassemia phenotype. Therefore, in high prevalence thalassemia regions, hereditary spherocytosis cases are often misdiagnosed. Here, a case once diagnosed as thalassemia, based on preliminary clinical examinations, underwent genetic testing in our laboratory, where analysis of globin gene mutations proved negative. We conducted both clinical and genetic analyses on the patient and his family. We collected clinical data, performed erythrocyte membrane protein analysis by SDS-PAGE and sequenced the ANK1 gene. We also investigated pathogenic mechanisms through cDNA sequencing and literature studies. From patient clinical data, we diagnosed the patient with moderate to severe hereditary spherocytosis, rather than thalassemia. SDS-PAGE data showed that Ankyrin protein expression was reduced. Sequencing of genomic DNA identified a frameshift mutation (ANK1:c.2394_2397del CAGT). cDNA sequencing showed that the expression of a mutant allele was significantly decreased. Our study corrected a clinical misdiagnosis and confirmed the diagnosis of hereditary spherocytosis in this patient. Identification of such causative mutations is important for accurate downstream patient therapy and is critically important for the prevention/detection of another affected birth. Additionally, the disruption of mRNA transcribed from the mutant allele resulted in a significant reduction in Ankyrin expression and was speculatively considered the pathogenic mechanism behind this mutation.


Assuntos
Anquirinas/genética , Nucleotídeos/genética , Deleção de Sequência/genética , Esferocitose Hereditária/diagnóstico , Esferocitose Hereditária/genética , Alelos , Criança , Erros de Diagnóstico , Mutação da Fase de Leitura/genética , Humanos , Masculino , Mutação/genética , Fenótipo , RNA Mensageiro/genética , Talassemia/genética
8.
Clin Nutr ; 39(1): 258-264, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30799192

RESUMO

BACKGROUND & AIMS: We aimed to examine the association between serum albumin (SAlb) and the development of chronic kidney disease (CKD), and examine any possible effect modifiers in general hypertensive patients with normal renal function and with no previous cardiovascular diseases (CVD). METHODS: This is a post-hoc analysis (performed at May, 2018) of 12,621 hypertensive adults with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and SAlb ≥35.0 g/L from the renal sub-study of the China Stroke Primary Prevention Trial (CSPPT), conducted from May 2008 to August 2013. The primary outcome was development of CKD, defined as a decrease in eGFR of ≥30% and to a level of <60 mL/min/1.73 m2; or end stage renal disease. RESULTS: The median follow-up duration was 4.4 years. Overall, the association between SAlb levels and risk of the primary outcome followed a U-shape. The risk of CKD development significantly decreased with the increment of SAlb (per g/L: OR = 0.92; 95% CI: 0.88-0.96) in participants with SAlb <51.4 g/L, and increased with the increment of SAlb (per g/L: OR = 1.06; 95%CI: 1.01-1.11) in participants with SAlb ≥51.4 g/L. Moreover, in participants with SAlb <51.4 g/L, the association between SAlb and CKD development remained significant in participants without proteinuria (per g/L: OR = 0.93; 95% CI: 0.88-0.99). The association between SAlb and CKD development was not significantly modified by age, sex, folic acid treatment, proteinuria, systolic blood pressure (SBP) at baseline and time-averaged SBP during the treatment period (all P-interactions>0.05). CONCLUSIONS: There was a U-shaped association between SAlb levels and risk of CKD development among general hypertensive patients with normal renal function and without CVD, with a turning point at about 51.4 g/L.

9.
Artif Cells Nanomed Biotechnol ; 48(1): 28-36, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852256

RESUMO

Traditional haemostatic materials generally have slow hemostasis rate and poor biocompatibility. This paper reports on the haemostatic properties and mechanism of silk fibroin (SF). SF-PEG sponge that could be solubilised and changed to gel form by blood was fabricated through mixing SF and polyethylene glycol (PEG, 1500 Da) followed by lyophilisation of the mixed solution. SF-PEG sponge, together with control samples of SF sponge (no PEG) and a commercially available haemostatic material, gelatine sponge, were subjected to the hemostasis tests using a liver trauma model of rabbit. The results showed that SF was superior to gelatine sponge in hemostasis time (136.17 ± 62.27 s and 249.83 ± 29.18 s) and blood loss (2.16 ± 1.27 g vs. 4.97 ± 1.44 g). Furthermore, in vitro experiments indicated SF-PEG sol-gel transition promoted platelet adhesion and aggregation, as well as platelet-fibrinogen interaction. Therefore, except for the physical blocking of bleeding port due to PEG-induced SF fast gelation, SF might also have an impact on blood coagulation process, a phenomenon that has not been reported before. In conclusion, SF is a new type of haemostatic material that might be able to meet the requirements of speed, efficiency and biosafety in a variety of clinical applications.

10.
Curr Pharm Des ; 25(46): 4919-4927, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31830892

RESUMO

BACKGROUND: Anthocyanins are a type of flavonoids that are natural water soluble glycosidic pigments with efficacious anti-cancer effects, which have good biological activity against many cancers including colorectal cancer (CRC). However, the exact molecular mechanism used by anthocyanins against cancer is unclear; it is also unclear what a reasonable dosage might be for their use against colorectal cancer. METHODS: Western blotting, immunohistochemistry, MTT assay, xenograft model, and hematoxylin-eosin (HE) staining were used to perform the experiments. RESULTS: Compared with the control group, anthocyanins could significantly inhibit the cell viability and proliferation and promote the apoptosis of human colon cancer HT29 cells. Furthermore, anthocyanins reduced tumor weight and volume in a colon tumor mouse model and downregulated the expression of PI3K protein, inhibited AKT expression and phosphorylation, decreased the Bcl-2 and Bax ratio and reduced survivin protein expression in the tumor tissue. CONCLUSION: Anthocyanins promoted apoptosis of CRC cells and inhibited colon cancer growth of xenografted tumors. Mechanistically, anthocyanins enhanced the Bcl-2/Bax and caspase-dependent apoptotic pathways through targeting the PI3K/AKT/survivin pathway, resulting in impairment of growth of CRC.

11.
J Hypertens ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31834125

RESUMO

OBJECTIVE: Data on the association between visit-to-visit variability (VVV) in blood pressure (BP) and the risk of stroke among hypertensive patients with chronic kidney disease (CKD) is limited. We aimed to evaluate the relation of VVV in BP with the risk of stroke, and examine any possible effect modifiers in hypertensive patients with mild-to-moderate CKD. METHODS: This is a post-hoc analysis of the China Stroke Primary Prevention Trial. A total of 3091 patients with estimated glomerular filtration rate 30-60 ml/min per 1.73 m and/or proteinuria at baseline, without occurring stroke and with BP measurements of at least two visits from randomization to the 12-month visit were included. The main VVV in BP was expressed as SD. The primary outcome was first stroke. RESULTS: The median subsequent treatment duration was 3.7 years. After multivariable adjustment, including baseline SBP and mean SBP during the first 12-month follow-up, there was a significantly positive relationship of SD SBP with the risk of subsequent first stroke (per SD increment; odds ratio, 1.41; 95% confidence interval: 1.17-1.69) and first ischemic stroke (odds ratio, 1.55; 95% confidence interval: 1.26-1.90). Results were consistent across various subgroups, including age, sex, baseline SBP, treatment compliance, and mean SBP, concomitant usage of calcium channel blocker during the first 12-month follow-up period. Similar trends were also found for coefficient of variation SBP, and SD or coefficient of variation DBP. However, there was no significant association between BP variability and first hemorrhagic stroke. CONCLUSION: In hypertensive adults with mild-to-moderate CKD, visit-to-visit variability in BP was significantly associated with the risk of subsequent first stroke.

12.
J Exp Clin Cancer Res ; 38(1): 500, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31861994

RESUMO

In the original publication of this article [1], the author found an error in Fig. 2f. lncGPR107 should be changed to lncMAPK6, and the corrected Fig. 2 is shown below.

13.
PLoS One ; 14(11): e0225261, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31751365

RESUMO

Human bocavirus (HBoV) is a member of the genus Bocavirus, family Parvoviridae, and subfamily Parvovirus and was first identified in nasopharyngeal aspirates of Swedish children with acute respiratory tract infection (ARTI) in 2005. It is the causative agent of nasopharyngeal aspirate disease and death in children. The HboV genomic structure is a linear single-stranded DNA (ssDNA). Its clinical pathogenic characteristics have been extensively studied, however, at present the molecular mechanism underlying the pathogenesis of HBoV infection is not completely clear. In this study, a total of 293 differentially expressed proteins (DEPs) between ARTI cases and healthy plasma samples were characterized using isobaric tags for relative and absolute quantitation (iTRAQ)-coupled bioinformatics analysis, among which 148 were up-regulated and 135 were down-regulated. Gene Ontology (GO) and Cluster of Orthologous Groups of proteins (COG) annotated an enrichment of DEPs in complement activation and biological processes like immunity, inflammation, signal transduction, substance synthesis, and metabolism. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis enriched DEPs mainly in the Wnt signaling pathway (ko04310), PPAR signaling pathway (ko03320), intestinal immune network for IgA production (ko04672), complement and coagulation cascades (ko04610), Toll-like receptor signaling pathway (ko04620) and B cell receptor signaling pathway (ko04662). Further, expression levels of three candidate proteins (upregulated PPP2R1A and CUL1, and downregulated CETP) were validated using western blotting. Our investigation is the first analysis of the proteomic profile of HBoV-infected ARTI cases using the iTRAQ approach, providing a foundation for a better molecular understanding of the pathogenesis of ARTI in children.

14.
Br J Nutr ; : 1-20, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31699171

RESUMO

Maintenance hemodialysis (MHD) is the use of a machine to filter wastes, salts and fluid from blood for at least 3 months to prolong the life of patients with advanced kidney failure. Although low dietary energy intake (DEI) has been observed in MHD patients, few studies have related DEI to the risk of mortality. To explore this relationship, a study included 1039 MHD patients from 8 centers was conducted. DEI was assessed by three 24-hour diet recalls including one dialysis day and two non-dialysis days, and was normalized to ideal body weight (IBW). All-cause mortality and CVD mortality were the primary and secondary outcomes, respectively. During a median follow-up of 28 months, all-cause and CVD mortality occurred in 230 (22.1%) and 140 (13.5%) participants. Overall, a U-shaped relationship was observed between DEI and all-cause or CVD mortality. The risk of all-cause mortality decreased significantly with the increase of DEI in participants with DEI <40kcal/kg IBW/d (HR, 0.98; 95% CI: 0.96-1.00) and increased significantly with the increase of DEI in those with DEI ≥40kcal/kg IBW/d (HR, 1.12; 95%CI: 1.04-1.20). Similarly, the risk of CVD mortality decreased with the increase of DEI in participants with DEI <36.5kcal/kg IBW/d (HR, 0.96; 95%CI: 0.93-0.99) and increased with the increase of DEI in participants with DEI ≥36.5kcal/kg IBW/d (HR, 1.11; 95%CI: 1.04-1.18). In summary, there was a U-shaped association between DEI and all-cause or CVD mortality, with a turning point at about 40 and 36.5 kcal/kg IBW/d, respectively, in MHD patients.

15.
Neuroscience ; 422: 21-31, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31682957

RESUMO

Growing evidence indicates that early-life inflammation has adverse effects on adult hippocampal neurogenesis and GABA system. Based the report that hippocampal GABA system is a key modulator in adult hippocampal neurogenesis, the aim of this study was to investigate whether and how early inflammation affects GABAergic system resulting in the alterations of adult hippocampal neurogenesis and related behaviors. Neonatal mice received a daily subcutaneous injection of lipopolysaccharide (LPS, 50 µg/kg) or saline on postnatal days (PND) 3-5. Behavioral tests were used to explore LPS-induced depression-like behaviors of adult mice. Immunohistochemistry staining and western blot were employed to detect adult neurogenesis, GABAergic system, glia activation and BDNF-TrkB pathway in the hippocampus. LPS-treated mice developed a depression phenotype with the inhibited maturation of hippocampal newborn neurons in adulthood. Compared with controls, LPS mice showed a decreased expression of GABAA receptor (GABAAR) protein. GABAAR agonist phenobarbital could rectify the decrease of BrdU+/NeuN+ cells in LPS mice. Additionally, postnatal LPS treatment resulted in the activation of astrocytes and the increase expression of toll-like receptor 4 (TLR4) in the second postnatal week and the downregulation of BDNF-TrkB pathway in adulthood. The treatment with TLR4 inhibitor TAK-242 restored the decrease of BrdU+/NeuN+ cells and depression-like behaviors in LPS mice via improving GABAAR. The results indicate that postnatal LPS exposure impairs adult hippocampal neurogenesis and causes depression-like behaviors through early astrocytes activation triggering the later GABAAR downregulation.

16.
J Food Biochem ; 43(12): e13061, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31612542

RESUMO

The capsaicin in hot peppers is an important biological active substance that is widely used in food and medicine. In this work, six capsaicin derivatives such as N-(4-Hydroxy-3-acetophenone benzyl)acrylamide (A), 2-hydroxy-3-(octyloxy)phenyl-5-acrylamidemethylbenzene phenyl methanone (B), N-(2,5-dihydroxybenzene)acetamide (C), N-(5-acetamidemethyl benzene-2,4-dihydroxybenzene)acetamide (D), 4-acetamideme thylbenzene-2-benzylphenol (E), and N-(2-methyl-4-hydroxy-5-methylthiobenzene)acetamide (F) were synthesized via the Friedel-Crafts (F-C) alkylation reaction and were characterized using IR, 1 H NMR, and HRMS. The antioxidant activity of compounds was evaluated using the reducing power and DPPH radical (DPPH·) scavenging assays, and Vitamin C (Vc) was used as a control. The antibacterial activity was tested using minimum inhibition concentration (MIC) and antibacterial rate assays, and Escherichia coli and Staphylococcus aureus were used as the tested strain. The results showed that all six capsaicin derivatives had certain antioxidant and antibacterial activities, and the activities increased with increasing mass concentration. The best properties were obtained for compounds C and F; the antioxidant activity of compound C was similar to Vc and the MIC of compound F was 0.0313 mg/ml, its antibacterial rate was greater than 99% at 3 mg/ml. PRACTICAL APPLICATIONS: As a vegetable, peppers can be eaten fresh or processed to other forms such as pepper powder or pepper jam, and it is very popular because of its long history, unique flavor, and special functions. Our current study shows that capsaicin derivatives have good antioxidant and antibacterial activities, and therefore, the present study of capsaicin derivatives with good activity provides a good foundation for future applications in natural food additives and medicine.

17.
Cell Death Dis ; 10(10): 774, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601780

RESUMO

Neonatal jaundice is prevalent among newborns and can lead to severe neurological deficits, particularly sensorimotor dysfunction. Previous studies have shown that bilirubin (BIL) enhances the intrinsic excitability of central neurons and this can potentially contribute to their overexcitation, Ca2+ overload, and neurotoxicity. However, the cellular mechanisms underlying elevated neuronal excitability remain unknown. By performing patch-clamp recordings from neonatal neurons in the rat medial vestibular nucleus (MVN), a crucial relay station for locomotor and balance control, we found that BIL (3 µM) drastically increases the spontaneous firing rates by upregulating the current-mediated voltage-gated sodium channels (VGSCs), while shifting their voltage-dependent activation toward more hyperpolarized potentials. Immunofluorescence labeling and western immunoblotting with an anti-NaV1.1 antibody, revealed that BIL elevates the expression of VGSCs by promoting their recruitment to the membrane. Furthermore, we found that this VGSC-trafficking process is Ca2+ dependent because preloading MVN neurons with the Ca2+ buffer BAPTA-AM, or exocytosis inhibitor TAT-NSF700, prevents the effects of BIL, indicating the upregulated activity and density of functional VGSCs as the core mechanism accountable for the BIL-induced overexcitation of neonatal neurons. Most importantly, rectification of such overexcitation with a low dose of VGSC blocker lidocaine significantly attenuates BIL-induced cell death. We suggest that this enhancement of VGSC currents directly contributes to the vulnerability of neonatal brain to hyperbilirubinemia, implicating the activity and trafficking of NaV1.1 channels as a potential target for neuroprotection in cases of severe jaundice.

18.
Medicine (Baltimore) ; 98(41): e17520, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593122

RESUMO

BACKGROUND: Evidence suggests that dry CO2 insufflation during laparoscopic colorectal surgery results in greater structural injury to the peritoneum and longer hospital stay than the use of warm, humidified CO2. We aimed to test the hypothesis that warm, humidified CO2 insufflation could reduce postoperative pain and improve recovery in laparoscopic colorectal surgery. METHODS: One hundred fifty elderly patients undergoing laparoscopic colorectal surgery under general anesthesia from May 2017 to October 2018 were randomly divided into 3 groups. The primary outcomes were resting pain, cough pain, and consumption of sufentanil at 2, 4, 6, 12, 24, and 48 hours postoperatively. Quality of visual image, hemodynamic changes, esophageal temperature, mean skin temperature, mean body temperature, recovery time, days to first flatus and solid food intake, shivering, incidence of postoperative ileus, length of hospital stay, surgical site infections, patients and surgeon satisfaction scores, adverse events, prothrombin time, activated partial thromboplastin time, and thrombin time were recorded. RESULTS: Group CE patients were associated with significantly higher early postoperative cough pain and sufentanil consumption than the other 2 groups (P < .05). Compared with group CE, patients in both groups WH and CF had significantly reduced intraoperative hypothermia, recovery time of PACU, days to first flatus and solid food intake, and length of hospital stay, while the satisfaction scores of both patients and surgeon were significantly higher (P < .05). Prothrombin time, activated partial thromboplastin time, and thrombin time were significantly higher in group CE from 60 minutes after pneumoperitoneum to the end of pneumoperitoneum than the other 2 groups (P < .05). The number of patients with a shivering grade of 0 was significantly lower and grade of 3 was significantly higher in group CE than in the other 2 groups (P < .05). CONCLUSION: Use of either warm, humidified CO2 insufflations or 20°C, 0% relative humidity CO2 combined with forced-air warmer set to 38°C during insufflations can both reduce intraoperative hypothermia, dysfunction of coagulation, early postoperative cough pain, sufentanil consumption, days to first flatus, solid food intake, and length of hospital stay.


Assuntos
Dióxido de Carbono/efeitos adversos , Cirurgia Colorretal/métodos , Laparoscopia/métodos , Peritônio/lesões , Idoso , Analgésicos Opioides/uso terapêutico , Cirurgia Colorretal/normas , Procedimentos Cirúrgicos do Sistema Digestório , Feminino , Humanos , Umidade/efeitos adversos , Hipotermia/etiologia , Insuflação/métodos , Tempo de Internação/estatística & dados numéricos , Masculino , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/prevenção & controle , Satisfação do Paciente/estatística & dados numéricos , Tremor por Sensação de Frio/fisiologia , Sufentanil/administração & dosagem , Sufentanil/uso terapêutico
19.
J Periodontol ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31471894

RESUMO

BACKGROUND: Hyperglycemic micro-environment induced by diabetes could regulate the response of periodontal tissues to pathogenic microorganisms in which disruption of autophagy lysosomal pathway (ALP) may participate. This study aimed to explore the mechanisms underlying how high glucose (HG) regulates ALP in gingival epithelial cells (GECs). METHODS: Human gingival tissues in healthy group (C), periodontitis group (P), diabetes group (DM), and diabetes + periodontitis group (DP) were collected and were applied to observe the fusion of autophagy and lysosome. Diabetic mouse model with periodontitis was established and RNA-seq was applied to investigate the expression of ALP-associated genes in gingival epithelium. To explore the key role of ATPase transmembrane v0 domain, subunit c (ATP6V0C) in the disruption of ALP by HG, human gingival epithelial cells (HGECs) were cultured in 5.5 mM/25 mM glucose medium for 48 hours and followed by Porphyromonas gingivalis stimulation for 0, 6, and 12 hours. HBLV-h-ATP6V0C was transfected in HGECs that were stimulated by 25 mM HG condition. RESULTS: Immunofluorescence double staining exhibited the disruption of ALP in human gingival epithelium in diabetes groups and HGECs under 25 mM glucose condition, accompanied with significantly downregulated lysosomal acidity. RNA-seq of mouse gingival epithelium screened out Atp6v0c. Compared with HGECs in normal culture medium, ATP6V0C expression and LC3-II/I expression ratio were significantly downregulated, with an upregulated expression of P62, IL-1ß in HGECs under HG condition. Over-expression of ATP6V0C rescued HG-induced disruption of ALP in HBLV-h-ATP6V0C transfected HGECs, with significantly upregulation of LC3-II/I and downregulation of P62, IL-1ß. CONCLUSION: ATP6V0C mediates HG-induced ALP disruption in HGECs, eventually exacerbates periodontal inflammation.

20.
Am J Transl Res ; 11(8): 5272-5283, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31497240

RESUMO

Babaodan capsule (BBD), a traditional Chinese (TCM) formula, has been widely used as an alternative remedy for multiple types of malignancies, clinically. However, the underlying mechanisms behind the efficacy of BBD remain poorly understood, particularly in regard to lung cancer. Herein, we demonstrate that BBD induced autophagic death in A549 and A549DDP cells without apoptosis. Treatment with autophagic inhibitor 3-MA, Baf-A1 and PI3K agonist, IGF-1, fully proved our conclusion, as well as uncovered the potential downregulated signaling pathway, PI3K/AKT/mTOR. The study additionally found that BBD could downregulate the expression of MDR1 and increase the chemosensitivity of cisplatin. Collectively, our results, both in vivo and in vitro, demonstrate that BBD leads to autophagic cell death through downregulating the PI3K/AKT/mTOR signaling pathway and improved the antitumor effects of cisplatin in non-small cell lung cancer (NSCLC).

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA