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1.
J Invertebr Pathol ; : 107356, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32199833

RESUMO

Ganglioneuritis was the primary pathologic change in infected abalone associated with Haliotid herpesvirus 1 (HaHV-1) infection, which eventually became known as abalone viral ganglioneuritis (AVG). However, the distribution of HaHV-1 in the other tissues and organs of infected abalone has not been systemically investigated. In the present study, the distribution of HaHV-1-CN2003 variant in different organs of small abalone, Haliotis diversicolor supertexta, collected at seven different time points post experimental infection, was investigated with histopathological examination and in situ hybridization (ISH) of HaHV-1 DNA. ISH signals were first observed in pedal ganglia at 48 hours post injection, and were consistently observed in this tissue of challenged abalone. At the same time, increased cellularity accompanied by ISH signals was observed in some peripheral ganglia of mantle and kidney. At the end of infection period, lesions and co-localized ISH signals in infiltrated cells were detected occasionally in the mantle and hepatopancreas. Transmission electron microscope analysis revealed the presence of herpes-like viral particles in haemocyte nuclei of infected abalone. Our results indicated that, although HaHV-1-CN2003 was primarily neurotropic, it could infect other tissues including haemocytes.

2.
Inflammation ; 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32198725

RESUMO

The therapeutic effect of electroacupuncture (EA) on inflammatory pain has been well recognized clinically, but the mechanism is unclear. Interleukin-10 (IL-10), which is produced by regulatory T (Treg) cell, is a key anti-inflammatory cytokine for relieving inflammatory pain. Therefore, the aim of this study is to investigate whether EA could inhibit CFA-induced pain and attenuate inflammation progression by regulating the activation of immunocyte and inducing the expression of IL-10. In this study, mice were treated with EA (2/100 Hz, 2 mA) for five consecutive days after 1 day of CFA injection. The behavioral tests were measured and analyzed after the daily EA treatment; then, hind paw, spinal cord, and spleen tissues were prepared for assessment. The results showed that EA treatment significantly increased the mechanical threshold and thermal latency after CFA injection and boosted the expression of IL-10 in paw and spinal cord tissues. EA treatment promoted Treg cells; suppressed macrophage and neutrophils cells; reduced the expression of IL-1ß, NLRP3, and TNF-α; and ultimately relieved inflammatory pain. The findings suggested that the analgesic and anti-inflammatory effect of EA treatment could be partially associated with suppression of pro-inflammatory cytokines mediated by induction of IL-10.

3.
PLoS One ; 15(3): e0229994, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32126125

RESUMO

BACKGROUND: Hepatitis C virus core antigen (HCV Ag) assay has been proposed as a more economical alternative to HCV RNA detection. This study aimed to investigate the clinical utility of HCV Ag assay in the monitoring of direct-acting antivirals (DAAs) for chronic hepatitis C patients. METHODS: We analyzed serum samples from 110 patients treated with paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD) with or without ribavirin. The levels for both HCV Ag and HCV RNA assessed by COBAS TaqMan HCV (CTM) Test or Abbott RealTime HCV (ART) assay were evaluated at baseline, week 2, 4, and 12 during treatment and 12 weeks after completion. RESULTS: Baseline HCV Ag levels showed good correlations with HCV viral load (r = 0.879; p<0.001); whereas the correlation was slightly stronger with CTM test than with ART assay (p = 0.074). The concordance of HCV Ag and HCV RNA undetectability was significantly better in CTM test than in ART assay at week 2 (p = 0.003) and week 4 (p = 0.003). A sustained viral response 12 weeks off therapy (SVR12) was achieved in 108 patients (98%); the HCV Ag assay identified 99% of these patients. Both undetectability of serum HCV Ag and HCV RNA had high positive predictive value at week 2 (98% vs. 100%) and at week 4 (97% vs. 99%) in predicting SVR12. CONCLUSIONS: HCV Ag assay may be a feasible alternative to HCV RNA for the determination of SVR12 in patients treated with DAAs.

4.
Calcif Tissue Int ; 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32179936

RESUMO

PURPOSE: This study aimed to compare the bone mineral density (BMD) of older women living in rural and urban areas, and evaluate the potential factors affecting the risk of osteoporosis. METHODS: We recruited 574 women aged 65 years or older from rural areas and 496 from urban areas in Shanghai, China. The BMD values of the lumbar vertebrae and total left hip were measured by a dual energy X-ray absorptiometry densitometer. We also recorded information about education level, family income, medications, reproductive and menstrual history, diet, smoking, and alcohol consumption. RESULTS: Women in urban areas had significantly higher BMD in their lumbar spine, and there was a dramatic increase in the proportion of women with osteoporosis in rural areas. The age at menarche was significantly higher among women living in rural areas, and there were more years from menarche to menopause among urban women. Rural women had significantly higher numbers of both pregnancies and parity, and a significantly lower age at first parity. In multiple linear regression analyses, years from menarche to menopause was independently related to high lumbar spine BMD, while age at menarche and parity was independently related to low lumbar spine BMD. CONCLUSION: More older women in rural areas had osteoporosis. Later menarche, less years from menarche to menopause and higher parity might partially contribute to decreased BMD among women in rural areas. More attention should be paid to women in rural areas to prevent bone loss and further bone and health impairment.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32163642

RESUMO

BACKGROUND: Ocular involvement can occur at any stage of syphilis. Prompt diagnosis and proper treatment of ocular syphilis are vital to avoid long-term consequences. OBJECTIVES: To describe the risk factors for ocular syphilis and clinical features of blindness caused by syphilis. METHODS: We report risk factors for ocular syphilis amongst patients seen at the Shanghai Skin Disease Hospital between October 2009 to October 2017. We identify patients with ocular syphilis resulting in blindness and report the clinical characteristics, laboratory findings and treatment outcomes of these patients. RESULTS: A total of 8310 new cases of syphilis were seen, of which 213 patients had ocular disease and 50 patients had blindness due to syphilis. Increasing age and higher RPR titers were associated with ocular involvement but there was no association with HIV status. Blindness in syphilis was restricted predominantly to patients with optic nerve involvement and not patients with isolated uveitis. Fifty patients (and a total of 67 eyes) met the WHO definition of blindness prior to treatment for syphilis. At the end of follow-up vision had improved in 24 of 67 eyes (35.8%) after treatment. Successful treatment of uveitis was associated with the best improvement in visual acuity, whilst patient with underlying optic atrophy prior to treatment had the worst visual outcome. CONCLUSIONS: Ocular involvement is an important manifestation of syphilis which may result in blindness. Our data demonstrates outcomes for ocular syphilis are poor if detected late; early recognition and diagnosis is therefore vital to avoid permanent visual loss.

6.
Environ Res ; 184: 109216, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32065977

RESUMO

The annual average concentration of fine particles (PM2.5) in Taiwan has been decreasing yearly. However, ambient haze has not abated and visibility is still poor. This study proposes a method for quantifying the source apportionment of ambient haze from various constituents, namely measured PM2.5, moisture, and secondary organic aerosols (SOA, represented by the sum of measured O3 and NO2 levels). This study's model-based demisting technology integrated image haze extracting technology with air quality monitoring data. The images for haze extraction were from the instant cameras of the Taiwan Environmental Protection Agency's air quality monitoring stations (AQMSs). Results indicate that haze constituents with the product of light extinction and scene depth have very high correlation (R2 ≥ 0.8452), which demonstrate that this quantification approach was successful. The contributions of ambient haze from various constituents had quarterly and regional variations in the eastern, northern, central, and southern regions of Taiwan, which are slightly, lowly, moderately, and heavily contaminated areas, respectively. Each area was assigned a selected representative AQMS to represent its ambient haze characteristics. Cases where the dominant contributors to haze were PM2.5, moisture, and SOA were studied, in addition to the event days of PM2.5 and ozone. We detail the limits of this approach, especially with regard to the use of images. This approach can help administrators understand the composition of ambient haze to generate effective haze strategies and policies. Residents can use this method to determine the health effects of daily haze.

7.
Life Sci ; 248: 117451, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32088213

RESUMO

AIMS: Electro-acupuncture pretreatment (EAP) plays a protective role in myocardial ischemia (MI) injury. However, the underlying mechanism remains unclear. A growing body of evidence suggests postinfarction inflammatory response directly affects the remodeling of ventricular function. The purpose of this study was to investigate whether EAP alleviates MI through NLRP3 inflammasome inhibition. MATERIALS AND METHODS: We constructed an AMI model by ligating the left anterior descending (LAD) coronary artery after 3 days of EAP with C57BL/6 mice. Echocardiography and TTC staining were employed to evaluate cardiac function and infarct size after 24 h of ischemia. HE staining and immunohistochemistry were employed to determine inflammatory level. Then, inflammasome activation was detected by western blotting, and macrophage polarization and neutrophil infiltration were observed by flow cytometry. KEY FINDINGS: Our preliminary findings showed that EAP reduced the infarct area and increased fractional shortening (FS) and ejection fraction (EF) and decreased the degree of inflammation after AMI injury. Meanwhile, EAP inhibited the expression of NLRP3, cleaved caspase-1 and IL-1ß in ischemia myocardial tissue, companied by inhibiting the expression of F4/80+, CD11b+, CD206low macrophages and activated M2 macrophage, and decreasing Ly-6G+CD11b+ neutrophils in ischemia myocardial and spleen tissue. SIGNIFICANCE: EAP inhibits the activation of NLRP3 inflammasome, promotes M2 polarization of macrophages and reduces the recruitment of neutrophils in damaged myocardium, thereby decreases the infarct size and improves the cardiac function.

8.
J Am Chem Soc ; 142(8): 3806-3813, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32023409

RESUMO

Photolabile groups offer promising tools to study biological processes with high spatial and temporal control. In the investigation, we designed and prepared several new glycine amide derivatives of Sanger's reagent and demonstrated that they serve as a new class of photocages for Zn2+ and an acetylcholinesterase (AChE) inhibitor. We showed that the mechanism for photocleavage of these substances involves initial light-driven cyclization between the 2,4-dinitrophenyl and glycine methylene groups to form acyl benzimidazole N-oxides, which undergo secondary photoinduced decarboxylation in association with rupture of an amide bond. The cleavage reactions proceed with modest to high quantum yields. We demonstrated that these derivatives can be used in targeted intracellular delivery of Zn2+, fluorescent imaging by light-triggered Zn2+ release, and regulation of biological processes including the enzymatic activity of carbonic anhydrase (CA), negative regulation of N-methyl-d-aspartate receptors (NMDARs), and pulse rate of cardiomyocytes. The successful proof-of-concept examples described above open a new avenue for using Sanger's reagent-based glycine amides as photocages for the exploration of complex cellular functions and signaling pathways.

9.
Mol Genet Genomic Med ; : e1184, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32100970

RESUMO

BACKGROUND: Panel-based targeted exome sequencing was used to analyze the genetic and clinical findings of targeted genes in a cohort of northeast Chinese with retinitis pigmentosa. METHODS: A total of 87 subjects, comprising 23 probands and their family members (total patients: 32) with confirmed retinitis pigmentosa were recruited in the study. Panel-based targeted exome sequencing was used to sequence the patients and family members, all subjects with retinitis pigmentosa underwent a complete ophthalmologic examination. RESULTS: Of the 23 probands, the clinical manifestations include night blindness, narrowing of vision, secondary cataracts, choroidal atrophy, color blindness, and high myopia, the average age of onset of night blindness is 12.9 ± 14 (range, 0-65; median, 8). Posterior subcapsular opacities is the most common forms of secondary cataracts (nine cases, 39.1%), and peripheral choroidal atrophy is the most common form of secondary choroidal atrophy (12 cases, 52.2%). Of these probands with complication peripheral choroidal atrophy, there were eight probands (66.7%, 8/12) caused by the pathogenic variation in USH2A gene. A total of 17 genes and 45 variants were detected in 23 probands. Among these genes, the commonest genes were USH2A (40%; 18/45), RP1 (15.6%; 7/45), and EYS (8.9%; 4/45), and the top three genes account for 56.5% (13/23) of diagnostic probands. Among these variants, comprising 22 (48.9%) pathogenic variants, 14 (31%) likely pathogenic variants, and nine (20%) uncertain clinical significance variants, and 22 variants was discovered first time. Most of the mutations associated with RP were missense (53.3%, 24/45), and the remaining mutation types include frameshift (35.6%, 16/45), nonsense (6.7%, 3/45), and spliceSite (4.4%, 2/45). Among the probands with mutations detected, compound heterozygous forms was detected in 13 (56.5%, 13/23) probands, and digenic inheritance (DI) forms was detected in five (21.7%, 5/23) probands. CONCLUSION: Panel-based targeted exome sequencing revealed 23 novel mutations, recognized different combinations forms of variants, and extended the mutational spectrum of retinitis pigmentosa and depicted common variants in northeast China.

10.
Br J Haematol ; 2020 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-32090321

RESUMO

Acute myeloid leukaemia (AML) patients with biallelic mutations of CEBPA (bi CEBPA) have a 30-50% relapse rate. This study established the value of mutations based on next-generation sequencing (NGS) and multiparameter flow cytometric measurable residual disease (MFC-MRD) detection and compared the outcomes. From 2014 to 2018, 124 newly diagnosed bi CEBPA AML patients were treated. The median age was 37·5 (16-69) years. The 3-year cumulative incidence of relapse (CIR), relapse-free survival (RFS) and overall survival (OS) were 33·0%, 64·7% and 84·3%, respectively. Patients without additional mutations and with GATA2 mutations were defined as 'NGS low risk', which was the only favourable independent factor for CIR and RFS of pretreatment parameters. Patients with sustained positive MRD after two consolidation cycles and MRD negative losses at any time were defined as 'MRD high risk', which was the only poor independent factor for CIR, RFS and OS, including pretreatment and post-treatment parameters. In CR2 and non-remission patients who underwent allo-HSCT, superior OS was achieved. We conclude that NGS low risk was a favourable factor in the analysis of pretreatment parameters. MRD risk stratification was an independent prognostic factor in pretreatment and post-treatment parameters. Relapsed patients still have a favourable outcome followed by allo-HSCT.

11.
J Neurosci ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32066583

RESUMO

Yes-associated protein (YAP) transcriptional coactivator is negatively regulated by the Hippo pathway and functions in controlling the size of multiple organs such as liver during development. However, it is not clear whether YAP signaling participates in the process of the formation of glia scars after spinal cord injury (SCI). In this study, we found that YAP was upregulated and activated in astrocytes of C57BL/6 male mice after SCI in a Hippo pathway dependent manner. Conditional knockout of YAP in astrocytes significantly inhibited astrocytic proliferation, impaired the formation of glial scars, inhibited the axonal regeneration, and impaired the behavioral recovery of C57BL/6 male mice after SCI. Mechanistically, the basic fibroblast growth factor (bFGF) was upregulated after SCI and induced the activation of YAP through RhoA pathways, thereby, promoting the formation of glial scars. Additionally, YAP promoted bFGF-induced proliferation by negatively controlling nuclear distribution of p27Kip1 mediated by CRM1. Finally, bFGF or XMU-MP-1 (an inhibitor of Hippo kinase MST1/2 to activate YAP) injection indeed activated YAP signaling, and promoted the formation of glial scars and the functional recovery of mice after SCI. These findings suggest that YAP promotes the formation of glial scars and neural regeneration of mice after SCI, and that the bFGF-RhoA-YAP-p27Kip1 pathway positively regulates astrocytic proliferation after SCI.SIGNIFICANCE STATEMENTGlial scars play critical roles in neuronal regeneration of central nervous system injury diseases such as spinal cord injury (SCI). Here, we provide evidence for YAP's function in the formation of glial scars after SCI through regulation of astrocyte proliferation. As a downstream of bFGF (which is upregulated after SCI), YAP promotes the proliferation of astrocytes through negatively controlling nuclear distribution of p27Kip1 mediated by CRM1. Activation of YAP by bFGF or XMU-MP-1 injection promotes the formation of glial scar and the functional recovery of mice after SCI. These results suggest that the bFGF-RhoA-YAP-p27Kip1 axis for the formation of glial scars may be a potential therapeutic strategy for SCI patients.

12.
Glia ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32057144

RESUMO

Olfactory ensheathing cells (OECs) are unique glial cells with axonal growth-promoting properties in the olfactory epithelium and olfactory bulb, covering the entire length of the olfactory nerve. The proliferation of OECs is necessary for the formation of the presumptive olfactory nerve layer (ONL) during development and OECs transplantation. However, the molecular mechanism underlying the regulation of OEC proliferation in the ONL still remains unknown. In the present study, we examined the role of sphingosine 1-phosphate (S1P) and S1P receptors (S1PRs) on OEC proliferation. Initially, reverse transcription-PCR (RT-PCR), western blot and immunostaining revealed that S1PRs were highly expressed in the OECs in vitro and in vivo. Furthermore, we found that S1P treatment promoted the proliferation of primary cultured OECs mediated by S1PR1. Mechanistically, yes-associated protein (YAP) was required for S1P-induced OEC proliferation through RhoA signaling. Finally, conditional knockout of YAP in OECs reduced OEC proliferation in ONL, which impaired the axonal projection and growth of olfactory sensory neurons, and olfactory functions. Taken together, these results reveal a previously unrecognized function of S1P/RhoA/YAP pathway in the proliferation of OECs, contributing to the formation of ONL and the projection, growth, and function of olfactory sensory neurons during development.

13.
J Viral Hepat ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32039536

RESUMO

Elbasvir/grazoprevir with or without ribavirin has excellent efficacy and safety for the treatment of hepatitis C virus (HCV) genotype 1 and 4 patients. The real-world experience has been reported but the detailed analysis of liver and renal adverse effects is lacking. This study evaluated the real-world experience relating to the effectiveness and liver/renal safety of elbasvir/grazoprevir in HCV genotype 1 patients with compensated liver disease. In the four medical centres of Chang Gung Medical System, 350 HCV genotype 1 patients with compensated liver disease who were treated with elbasvir/grazoprevir were enrolled. Clinical characteristics and laboratory data were collected. The effectiveness (sustained virologic response 12 weeks after end of treatment, SVR12) and safety were assessed. A consecutive series of 350 patients with a mean age of 68.8 ± 10.0 years old were enrolled. The majority were treatment-naïve (72.3%), genotype 1b (97.7%) and advanced fibrosis/cirrhosis (94.3%). Seventy-nine (22.6%) had hepatocellular carcinoma and 23 (6.6%) had coinfection with hepatitis B. The effectiveness of SVR12 was 94.6% (95% CI: 92.2%-97.0%) in the full analysis set and 99.1% (95% CI: 98.1%-100.1%) in the per-protocol set. There were two relapses and one nonresponder. Seven (2.0%) patients had adverse events resulting in premature discontinuation of treatment. Five of them were considered drug-related. One was due to autoimmune hepatitis. Contrary to previous reports, around 49% of ALT elevation was observed after 8 weeks, and in two patients was due to hepatitis B flares. As to the renal function during the course of therapy, a minor deterioration of eGFR was observed in patients with baseline eGFR ≥60 mL/min/1.73 m2 , but not in those with baseline eGFR <60, <60-30 or <30 mL/min/1.73 m2 . In this real-world data, elbasvir/grazoprevir was effective with few liver/renal adverse effects. One patient developed autoimmune hepatitis.

14.
Ying Yong Sheng Tai Xue Bao ; 31(1): 189-198, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31957396

RESUMO

To explore the alleviation effect of spraying phytohormone on physiological characteristics and yield of sweet potato under drought stress in different periods, and to determine the best period of spraying external plant hormones, the effects on endogenous hormone content, photosynthetic fluorescence characteristics and yield of sweet potato were examined by spraying 6-benzylaminopurine (6-BA), α-naphthylacetic acid (NAA) and abscisic acid (ABA) respectively under drought stress after transplanting for 20 days (early stage), 60 days (middle stage) and 100 days (later stage) under artificial water control. The results showed that compared with spraying water, exogenous phytohormones significantly increased the yield of sweet potato under drought stress, among which 6-BA had the highest effect, followed by NAA and ABA. The effect of spraying in early stage was better than that in middle and late stages. Exogenous phytohormones significantly increased photosynthetic and chlorophyll fluorescence parameters of sweet potato leaves under drought stress at different stages, alleviated the decrease in eatin ribonucleoside (ZR) and auxin (IAA) caused by drought. Stepwise regression analysis showed that endogenous hormones and photosynthetic characteristics were key factors affecting yield of sweet potato. Results of path analysis showed that spraying exogenous plant hormone affected sweet potato yield by changing net photosynthetic rate (Pn), IAA, ZR, maximal photochemical efficiency and photochemical performance index under drought stress at early stage. Therefore, spraying 6-BA could regulate the content of endogenous hormones and improve photosynthetic characteristics of sweet potato at the early growth stage, and thus effectively alleviate the loss of yield caused by drought stress.


Assuntos
Secas , Ipomoea batatas , Ácido Abscísico , Fotossíntese , Reguladores de Crescimento de Planta , Folhas de Planta , Estresse Fisiológico , Água
15.
Invest New Drugs ; 38(1): 202-210, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31701431

RESUMO

This study was done to elucidate the influence of direct-acting antiviral (DAA) agents on the recurrence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related HCC (HCV-HCC) after curative therapies. HCV-HCC patients who received curative therapies and obtained a complete response were analyzed. From January 2017 to September 2017, 112 HCV-HCC patients received DAA and obtained a sustained virological response (SVR). From January 2006 to December 2014, another 345 HCV-HCC patients received peg-interferon-based treatment and 118 obtained SVR. From January 2012 to December 2016, 248 HCV-HCC patients had complete HCC response and did not receive antiviral treatment. Patients were divided into DAA, IFN, and Untreated groups based on what antiviral treatment they received. There were 82 patients in the DAA group, 80 patients in the IFN group, and 160 patients in the Untreated group. During the follow-up period, the DAA group had 22 (26.8%) recurrent cases, whereas the IFN group had 46 (56.8%) cases after antiviral treatment. Among the 22 recurrent cases in the DAA group, 19 (86.9%) experienced HCC recurrence during 1 year after DAA initiation. Compared with the IFN group, the DAA group had poorer one-year recurrence-free survival (75.4% vs. 95%, p < 0.001), even after adjustment with propensity score matching (81.4% vs. 93.9%, p = 0.034). However, DAA was an improving factor for HCC recurrence compared with the Untreated group in the multivariate analysis. Among HCV-HCC patients with complete treatment, those with DAA-induced SVR had a higher one-year recurrence rate than those who received IFN-based antiviral therapy, but DAA did not seem to increase HCC recurrence compared to untreated patients.

16.
J Investig Med ; 68(1): 52-59, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31371390

RESUMO

Long non-coding RNAs (lncRNAs) have proved to act as crucial biomarkers in tumors. Novel biomarkers in non-small cell lung cancer (NSCLC) need to be investigated badly. To identify the differentially expressed lncRNAs between NSCLC tissue and adjacent tissue, microarray analysis was performed. lncRNA SLC16A1-AS1 was significantly less expressed in NSCLC tissue than that in adjacent tissue. Gain-of-function experiments was performed to determine the biological functions of SLC16A1-AS. In situhybridization and survival analysis were applied in lung cancer tissue samples to determine the prognostic role of SLC16A1-AS1. It was showed that SLC16A1-AS1 was remarkably downregulated in NSCLC tissues and cell lines. Functionally, SLC16A1-AS1 overexpression could inhibit the viability and proliferation of lung cancer cell, block the cell cycle and promote cell apoptosis in vitro which may result from reduced phosphorylation of rat sarcoma (RAS)/ proto-oncogene serine/threonine-protein kinase (RAF)/ mitogen-activated protein kinase kinase (MEK)/ extracellular regulated protein kinases (ERK) pathway caused by elevated expression of SLC16A1-AS1. Clinical sample analysis showed that SLC16A1-AS1 had a favorable impact on the overall survival and progression-free survival of patients with NSCLC. Our results suggested that SLC16A1-AS1 may act as a potential biomarker for patients with NSCLC.

17.
J Formos Med Assoc ; 119(1 Pt 3): 532-537, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31445848

RESUMO

BACKGROUND/PURPOSE: The major dose-limiting toxicity of ribavirin is hemolytic anemia. We investigated the incidence, risk factors and impact on virological response of anemia in chronic hepatitis C genotype 2 patients receiving sofosbuvir plus ribavirin therapy. METHODS: This was a retrospective real-world analysis of a single center including 293 chronic hepatitis C genotype 2 patients treated with sofosbuvir plus ribavirin for 12 weeks. Severe anemia was defined as hemoglobin concentration <10 g/dl. RESULTS: Treatment was completed in 285 (97%) of patients, of whom one withdrew due to severe anemia. Ribavirin dose reduction was required in 88 (30%) of patients. After excluding those with baseline hemoglobin <10 g/dl, 79 (29%) patients had developed severe anemia during therapy. Stepwise logistic regression analysis identified that chronic kidney disease (odds ratio [OR] = 3.970, p < 0.001), baseline hemoglobin level (OR = 0.475, p < 0.001) and baseline platelet count (OR = 0.992, p = 0.022) were independent factors. The sustained viral response 12 weeks off therapy (SVR12) rate was 93.9% in the per-protocol population. Multivariate analyses showed that history of hepatocellular carcinoma significantly reduced the efficacy of sofosbuvir plus ribavirin therapy (OR = 0.172, p = 0.001). Severe anemia, dose reduction or average dose (mg/kg/day) of ribavirin was not associated with SVR12. CONCLUSION: Severe anemia was not uncommon during sofosbuvir plus ribavirin therapy for chronic hepatitis C genotype 2 patients. Careful monitoring of anemia is necessary in patients with chronic kidney disease and low baseline hemoglobin level and platelet count.

18.
J Formos Med Assoc ; 119(1 Pt 3): 504-508, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31350109

RESUMO

BACKGROUND AND PURPOSE: Hepatitis C virus (HCV) core antigen is highly sensitive and specific in viremic HCV diagnosis. This study evaluated the cost-effectiveness of HCV core antigen (HCVcAg) in community-based screening for active HCV infection. METHODS: Between 2017/07 and 2018/07, community-based screenings for active HCV infection with two-step (anti-HCV for screening and HCVRNA for diagnosis) and one-step processes (HCVcAg for screening and diagnosis) were conducted in two districts in Kaohsiung City. While HCVcAg test was positive at ≥3 fmol/L, the lowest level of HCV-RNA detection was 12 IU/mL. We analyzed the cost-effectiveness of two algorithms in identifying active HCV infection. RESULTS: There were two large-scale screenings using the two-step process with a total of 2452 residents enrolled; while six hundred and forty-four residents participated in continuous small-scale screening with the one-step process. The prevalence of anti-HCV and positive HCVcAg was 3.4% and 2.8%. The viremic rate was 1.4% and 2.8% for two- and one-step processes (p < 0.001). While all positive HCVcAg were viremic, 42.4% of positive anti-HCV patients had viremia. The positive predictive value was 42.2% and 100% for two- and one-step processes in detecting active HCV infection (p < 0.001). In identifying one active HCV infection, the cost was $755.3 and $711.1 dollars for two- and one-step processes respectively. CONCLUSION: Compared to the two-step process in community-based screening, continuous screening with the HCVcAg test as a one-step tool for active HCV infection was cost-effective in areas with low seroprevalence of HCV in Taiwan.

19.
J Cell Biochem ; 121(1): 152-164, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31318102

RESUMO

Postmenopausal women undergo rapid bone loss, which caused by the accelerated osteoclastic bone resorption. Receptor activator of nuclear factor kappa-B ligand (RANKL) plays critical and essential roles on varied stages of osteoclastogenesis. Oleanolic acid (OA), a naturally derived small compound, has been found suppress osteoclastogenesis in early stage of bone marrow macrophages (BMMs). However, whether OA also regulates the late stage of osteoclastogenesis remains unclear. Here, the regulatory effect of OA on the late stage of osteoclastogenesis was investigated in vitro using RANKL-pretreated BMMs and in vivo using osteoprotegerin (OPG) knockout mice. Our in vitro studies demonstrate that OA inhibits the late stage of osteoclastogenesis from RANKL-pretreated BMMs. For in vivo animal investigation, OA attenuates the bone loss phenotypes in OPG-knockout mice by decreasing the densities of osteoclast, which are in consistent with the finding with in vitro osteoclastogenesis. Mechanistic investigations found that OA largely inhibit the activity of c-Fos and Nuclear factor of activated T-cells c1 (NFATc1) with RANKL-pretreated BMMs and OPG-knockout mice. Furthermore, OA suppresses the activities of osteoclast genes, such as Tartrate resistant acid phosphatase (TRAP), CathepsinK (Ctsk), and Matrix metalloproteinase 9 (MMP9). Taken together these findings, they have not only defined an inhibitory effect of OA in the late stage of osteoclastogenesis but have also gained new molecular mechanisms underlying the process of osteoclast formation.

20.
Ann Transl Med ; 7(20): 559, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31807540

RESUMO

Background: Autophagy has increasingly been recognized as playing an essential role in the pathogenesis of myocardial ischemia reperfusion injury (MIRI). Moxibustion, a form of heat therapy commonly used in traditional Chinese medicine (TCM), has been shown to exhibit cardioprotective effects. However, whether the cardioprotective effect of moxibustion is related to the regulation of autophagy remains unknown. This study aimed to investigate the possible mechanism underlying the cardioprotective effect of moxibustion preconditioning at PC6 on MIRI by measuring the expressions of proteins involved in the regulation of autophagy. Methods: Male Sprague-Dawley rats were randomly divided to receive moxibustion preconditioning or autophagy inhibitor 3-Methyladenine (3-MA) intervention. Then the MIRI model was established by ligating the left anterior descending (LAD) coronary artery for 30 minutes followed by reperfusion for 4 hours. After 4 hours of reperfusion, the myocardial infarction area was assessed using Evans blue and TTC staining, and cTnT and lactate dehydrogenase (LDH) levels in the serum were determined by ELISA. Hematoxylin and eosin (H&E) staining was performed for morphological evaluation of ventricular tissues. Expressions of autophagy components Beclin 1, Bcl-2, and Akt were assessed using quantitative real-time PCR, immunohistochemistry (IHC) and western blot. Results: Moxibustion preconditioning significantly reduced the necrotic area and the levels of cTnT and LDH were similar to the 3-MA intervention, also attenuated morphological alterations were induced by MIRI. Simultaneously, the mRNA and protein expressions of Beclin 1 and Akt were up-regulated, while those of Bcl-2 were down-regulated by MIRI. Moxibustion preconditioning and 3-MA intervention reversed MIRI-induced changes in Beclin 1, Akt, and Bcl-2 expressions. Conclusions: Moxibustion preconditioning at PC6 can attenuate myocardial injury for MIRI in a similar way to 3-MA intervention. This cardioprotective effect of moxibustion preconditioning may be mediated by modulating autophagy via regulation of Beclin 1, Bcl-2 and Akt.

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