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1.
J Chin Med Assoc ; 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33901125

RESUMO

BACKGROUND: Over recent years, new evolution in guideline-directed medical therapy (GDMT) contributes to clinical benefits in patients with heart failure and reduced ejection fraction (HFrEF). The additional medical expenditure may be a concern due to the current financial constraint. This study aimed to investigate the medical costs and clinical effectiveness of contemporary GDMT in recently hospitalized HFrEF patients. METHODS: Acutely decompensated hospitalized HFrEF patients from two multicenter cohorts of different periods were retrospectively analyzed. A propensity score matching was performed to adjust the baseline characteristics. Annual medication costs, risks of mortality, and recurrent heart failure hospitalizations (HFH) were compared. RESULTS: Following 1:2 propensity score matching, there were 426 patients from the 2017-2018 cohort using sacubitril/valsartan, while 852 patients from 2013-2014 did not use so at discharge. Baseline characteristics were similar, whereas the sacubitril/valsartan users were more likely to receive beta-blockers, ivabradine and mineralocorticoid receptor antagonists at discharge (79.3% vs. 60.4%, 23.2% vs. 0%, and 64.1% vs. 49.8%, p < 0.001). The 2017-2018 cohort produced more medication costs by 1,277 USD per person per year, while it resulted in lower rates of HFH and all-cause mortality (10.3 vs. 20.3 and 48.8 vs. 79.9 per 100 person-year, p < 0.001). Costs of preventing a mortality event and a HFH event with contemporary treatments were 15,758 USD (95% confidence interval [CI] 10,436-29,244) and 5,317 USD (95% CI 3,388-10,098), respectively. CONCLUSION: The higher adoption of GDMT was associated with greater medical expenses but better clinical outcomes in recently decompensated HFrEF patients.

2.
Aging (Albany NY) ; 13(7): 9265-9276, 2021 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-33780352

RESUMO

BACKGROUND: Dysregulated immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are thought to underlie the progression of coronavirus disease 2019 (COVID-19). We sought to further characterize host antiviral and cytokine gene expression in COVID-19 patients based on illness severity. METHODS: In this case-control study, we retrospectively analyzed 46 recovered COVID-19 patients and 24 healthy subjects (no history of COVID-19) recruited from the Second People's Hospital of Fuyang City. Blood samples were collected from each study participant for RNA extraction and PCR. We assessed changes in antiviral gene expression between healthy controls and patients with mild/moderate (MM) and severe/critical (SC) disease. RESULTS: We found that type I interferon signaling (IFNA2, TLR8, IFNA1, IFNAR1, TLR9, IRF7, ISG15, APOBEC3G, and MX1) and genes encoding proinflammatory cytokines (IL12B, IL15, IL6, IL12A and IL1B) and chemokines (CXCL9, CXCL11 and CXCL10) were upregulated in patients with MM and SC disease. Moreover, we found that IFNA1, apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G (APOBEC3G), and Fas-associated protein with death domain (FADD) were significantly downregulated (P < 0.05) in the SC group compared to the MM group. We also observed that microRNA (miR)-155 and miR-130a levels were markedly higher in the MM group compared to the SC group. CONCLUSION: COVID-19 is associated with the activation of host antiviral genes. Induction of the IFN system appears to be particularly important in controlling SARS-CoV-2 infection, as decreased expression of IFNA1, APOBEC3G and FADD genes in SC patients, relative to MM patients, may be associated with disease progression.

3.
ESC Heart Fail ; 8(2): 1204-1215, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33410280

RESUMO

AIMS: Ivabradine and sacubitril/valsartan are second-line therapies for patients with heart failure and reduced ejection fraction (HFrEF) based on guideline recommendations. We aimed to evaluate the synergistic effects of these two medications. METHODS AND RESULTS: Patients' data were extracted from a multicentre database between 2016 and 2018. Patients were classified into (1) Simultaneous group: simultaneous prescription of ivabradine and sacubitril/valsartan within 6 weeks; (2A) Sequential group, ivabradine-first: ivabradine was prescribed first, followed by sacubitril/valsartan; and (2B) Sequential group, sacubitril/valsartan-first: sacubitril/valsartan was prescribed first, followed by ivabradine. A total of 464 patients with HFrEF were enrolled. Cardiovascular death and/or unplanned re-hospitalizations for HF were less frequent (28.6% vs. 44.8%, P = 0.01), and the improvement of left ventricular ejection fraction (LVEF) was significantly greater in patients from the Simultaneous group than those from the Sequential group (∆LVEF 12.8 ± 12.9% vs. 9.3 ± 12.6%, P = 0.007). Among Sequential subgroups, the ivabradine-first treatment decreased heart rate and increased systolic blood pressure (SBP) compared with sacubitril/valsartan-first treatment (∆heart rate -9.1 ± 12.9 b.p.m. vs. 2.6 ± 16.0 b.p.m., P < 0.001; ∆SBP 4.6 ± 16.5 mmHg vs. -4.8 ± 17.2 mmHg, P < 0.001), whereas sacubitril/valsartan-first treatment showed a higher degree of LVEF improvement (∆LVEF 3.6 ± 7.8% vs. 0.7 ± 7.7%, P = 0.002) than ivabradine-first treatment. At the end of follow-up, SBP, LVEF, and left ventricular volume were comparable between two Sequential subgroups. CONCLUSIONS: Among patients with HFrEF, simultaneous rather than sequential treatment with sacubitril/valsartan and ivabradine was a better strategy to reduce adverse events and achieve left ventricular reverse remodelling. Ivabradine treatment had a more significant benefit on improving haemodynamic stability, whereas sacubitril/valsartan treatment showed a more significant effect on improving LVEF.

4.
J Cell Mol Med ; 25(3): 1568-1582, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33410581

RESUMO

The pro-inflammatory and pro-fibrotic liver microenvironment facilitates hepatocarcinogenesis. However, the effects and mechanisms by which the hepatic fibroinflammatory microenvironment modulates intrahepatic hepatocellular carcinoma (HCC) progression and its response to systematic therapy remain largely unexplored. We established a syngeneic orthotopic HCC mouse model with a series of persistent liver injury induced by CCl4 gavage, which mimic the dynamic effect of hepatic pathology microenvironment on intrahepatic HCC growth and metastasis. Non-invasive bioluminescence imaging was applied to follow tumour progression over time. The effect of the liver microenvironment modulated by hepatic injury on sorafenib resistance was investigated in vivo and in vitro. We found that the persistent liver injury facilitated HCC growth and metastasis, which was positively correlated with the degree of liver inflammation rather than the extent of liver fibrosis. The inflammatory cytokines in liver tissue were clearly increased after liver injury. The two indicated cytokines, tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6), both promoted intrahepatic HCC progression via STAT3 activation. In addition, the hepatic inflammatory microenvironment contributed to sorafenib resistance through the anti-apoptotic protein mediated by STAT3, and STAT3 inhibitor S3I-201 significantly improved sorafenib efficacy impaired by liver inflammation. Clinically, the increased inflammation of liver tissues was accompanied with the up-regulated STAT3 activation in HCC. Above all, we concluded that the hepatic inflammatory microenvironment promotes intrahepatic HCC growth, metastasis and sorafenib resistance through activation of STAT3.

5.
Sci Adv ; 6(51)2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33328239

RESUMO

Emerging and reemerging infections present an ever-increasing challenge to global health. Here, we report a nanoparticle-enabled smartphone (NES) system for rapid and sensitive virus detection. The virus is captured on a microchip and labeled with specifically designed platinum nanoprobes to induce gas bubble formation in the presence of hydrogen peroxide. The formed bubbles are controlled to make distinct visual patterns, allowing simple and sensitive virus detection using a convolutional neural network (CNN)-enabled smartphone system and without using any optical hardware smartphone attachment. We evaluated the developed CNN-NES for testing viruses such as hepatitis B virus (HBV), HCV, and Zika virus (ZIKV). The CNN-NES was tested with 134 ZIKV- and HBV-spiked and ZIKV- and HCV-infected patient plasma/serum samples. The sensitivity of the system in qualitatively detecting viral-infected samples with a clinically relevant virus concentration threshold of 250 copies/ml was 98.97% with a confidence interval of 94.39 to 99.97%.

6.
Am J Cancer Res ; 10(10): 3106-3126, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33163260

RESUMO

Amino acid transporters mediate substrates across cellular membranes and their fine-tuned regulations are critical to cellular metabolism, growth, and death. As the functional component of system Xc-, which imports extracellular cystine with intracellular glutamate release at a ratio of 1:1, SLC7A11 has diverse functional roles in regulating many pathophysiological processes such as cellular redox homeostasis, ferroptosis, and drug resistance in cancer. Notably, accumulated evidence demonstrated that SLC7A11 is overexpressed in many types of cancers and is associated with patients' poor prognosis. As a result, SLC7A11 becomes a new potential target for cancer therapy. In this review, we first briefly introduce the structure and function of SLC7A11, then discuss its pathological role in cancer. We next summarize current available data of how SLC7A11 is subjected to fine regulations at multiple levels. We further describe the potential inhibitors of the SLC7A11 and their roles in human cancer cells. Finally, we propose novel insights for future perspectives on the modulation of SLC7A11, as well as possible targeted strategies for SLC7A11-based anti-cancer therapies.

7.
Risk Manag Healthc Policy ; 13: 2309-2316, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33149711

RESUMO

Background: The diagnosis of postpartum pelvic organ prolapse (POP) relies on symptoms combined with pelvic organ prolapse-quantification (POP-Q) and lacks serological indicators. The objective of this study was to assess serum elastin, type I collagen, miRNA-30d, and miRNA-181a in the early postpartum period to identify hematologic predictors of POP. Material and Methods: The study included 1013 42- to 60-day-postpartum women who had delivered at Quanzhou Women's and Children's Hospital from October 1, 2016, to October 31, 2017. This study was performed in accordance with the Declaration of Helsinki. The pregnancy and childbirth characteristics and pelvic floor function were evaluated. Forty cases with and without POP were matched, and serum elastin and type I collagen were determined by enzyme-linked immunosorbent assay (ELISA). Reverse-transcription polymerase chain reaction (RT-PCR) was used to detect miRNA-30d and miRNA-181a in 15 pairs. Results: Of the 1013 women recruited, 699 (69.00%) were diagnosed with POP. The mean age was 29.00 years old, and the mean body mass index (BMI) was 22.6 kg/m2. In the univariate analysis, age ≥35 years (OR, 1.449; 95% CI, 0.965, 2.298), postpartum BMI ≥ 24 (OR, 4.402; 95% CI, 2.657, 6.148), neonatal weight ≥4 kg (OR, 4.832; 95% CI, 1.373, 17.290) and vaginal delivery (OR, 2.751; 95% CI, 1.855, 4.081) were risk factors for postpartum POP. There were no significant differences in the concentrations of serum elastin and type I collagen between the groups (P=0.52; P=0.26). There were significant differences in the concentrations of miRNA-30d and miRNA-181a between the groups (P=0.004; P=0.003). Conclusion: miRNA-30d and miRNA-181a tended to be increased in women with POP and could be potential clinical predictors.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33119090

RESUMO

AIMS: Although the beneficial effect of sacubitril/valsartan (SAC/VAL) compared to enalapril was consistent across ischaemic (ICM) and non-ischaemic cardiomyopathy (NICM) groups, the PARADIGM-HF study did not analyze the effect of ventricular remodelling on patients with different etiologies, which may affect clinical treatment outcomes. This study aimed to compare left ventricular ejection fraction (LVEF) following SAC/VAL treatment and its association with clinical outcomes. METHODS AND RESULTS: A total of 1,576 patients were analyzed. Patients were grouped by LVEF changes following SAC/VAL treatment for 8-month period. LVEF improvement ≥15% was defined as "significant improvement", and <5% or worse was classified as "lack of improvement". The primary outcome was a composite of cardiovascular death and unplanned hospitalization for heart failure.Patients with NICM had lower baseline LVEF but improvement was significantly greater comparing to those with ICM (baseline 28.0 ± 7.7% vs. 30.1 ± 7.1%, p < 0.001, LVEF increase of 11.1 ± 12.6% vs. 6.7 ± 10.2%, p < 0.001). The effect of functional improvement of SAC/VAL on NICM patients showed bimodal distribution. Primary endpoints were inversely associated with LVEF changes in NICM patients: adjusted hazard ratio was 0.42 (95% confidence interval [CI] 0.31-0.58, p < 0.001) for NICM patients with significant improvement, and was 1.73 (95% CI 1.38-2.16, p < 0.001) for NICM patients but lack of improvement. Primary endpoints of ICM patients did not demonstrate an association with LVEF changes. CONCLUSION: Patients with NICM had higher degree of LVEF improvement than those with ICM following SAC/VAL treatment, and significant improvement of LVEF in NICM patients indicates favorable outcome.

9.
Circ J ; 84(10): 1679-1685, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32908073

RESUMO

The health crisis due to coronavirus disease 2019 (COVID-19) has shocked the world, with more than 1 million infections and casualties. COVID-19 can present from mild illness to multi-organ involvement, but especially acute respiratory distress syndrome. Cardiac injury and arrhythmias, including atrial fibrillation (AF), are not uncommon in COVID-19. COVID-19 is highly contagious, and therapy against the virus remains premature and largely unknown, which makes the management of AF patients during the pandemic particularly challenging. We describe a possible pathophysiological link between COVID-19 and AF, and therapeutic considerations for AF patients during this pandemic.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Antiarrítmicos/uso terapêutico , Anticoagulantes/uso terapêutico , Antivirais/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Fibrilação Atrial/fisiopatologia , Ablação por Cateter/métodos , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Citocinas/sangue , Interações Medicamentosas , Humanos , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Risco
10.
Arrhythm Electrophysiol Rev ; 9(2): 54-60, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32983525

RESUMO

With catheter ablation becoming effective for non-pharmacological management of AF, many cases of atrial tachycardia (AT) after AF ablation have been reported in the past decade. These arrhythmias are often symptomatic and respond poorly to medical therapy. Post-AF-ablation ATs can be classified into the following three categories: focal, macroreentrant and microreentrant ATs. Mapping these ATs is challenging because of atrial remodelling and its complex mechanisms, such as double ATs and multiple-loop ATs. High-density mapping can achieve precise identification of the circuits and critical isthmuses of ATs and improve the efficacy of catheter ablation. The purpose of this article is to review the mechanisms, mapping and ablation strategy, and outcome of ATs after AF ablation.

11.
Cancer Cell Int ; 20: 421, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32868973

RESUMO

Background: New screening techniques may affect the optimal approaches for the prevention of cervical cancer. We evaluated the cost-effectiveness and accuracy of alternative screening strategies to provide evidence for cervical cancer screening guidelines in China. Methods: In total, 32,306 women were enrolled. The current screening with Cervista® high-risk human papillomavirus (HR-HPV) nongenotyping and cytology cotesting (Cervista® cotesting) was compared with PCR-reverse dot blot HR-HPV genotyping and cytology cotesting (PCR-RDB cotesting). All eligible participants were divided into Arm 1, in which both HR-HPV assays were performed, and Arms 2 and 3, in which the PCR-RDB HPV or Cervista® HR-HPV assay, respectively, was performed. Outcome indicators included the cases, sensitivity, negative predictive value (NPV), colposcopy referral rate and cost of identifying cervical intraepithelial neoplasia of grade 2/3 or worse (CIN2+/CIN3+). Results: Among the eligible participants, 18.4% were PCR-RDB HR-HPV-positive, while 16.9% were Cervista® HR-HPV-positive, which reflects good agreement (k = 0.73). PCR-RDB cotesting identified more CIN3+ cases than Cervista® cotesting in the first round of screening in Arm 1 (37 vs 32) and Arms 2/3 (252 vs 165). The sensitivity and NPV of PCR-RDB cotesting for identifying CIN3+ in Arm 1 (sensitivity: 94.9% vs 86.5%; NPV: 99.9% vs 99.7%) and Arms 2/3 (sensitivity: 95.1% vs 80.9%; NPV: 99.9% vs 99.6%) were higher than those of Cervista® cotesting, but the cost was similar. Conclusions: The PCR-RDB HR-HPV genotyping and Cervista® HR-HPV assay results were consistent. PCR-RDB cotesting possesses optimal cost-effectiveness for cervical cancer screening in China, which has the highest number of cases globally but low screening coverage.

12.
Am J Pathol ; 190(11): 2267-2281, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32805235

RESUMO

Liver fibrosis is an increasing health problem worldwide, for which no effective antifibrosis drugs are available. Although the involvement of aerobic glycolysis in hepatic stellate cell (HSC) activation has been reported, the role of pyruvate kinase M2 (PKM2) in liver fibrogenesis still remains unknown. We examined PKM2 expression and location in liver tissues and primary hepatic cells. The in vitro and in vivo effects of a PKM2 antagonist (shikonin) and its allosteric agent (TEPP-46) on liver fibrosis were investigated in HSCs and liver fibrosis mouse model. Chromatin immunoprecipitation sequencing and immunoprecipitation were performed to identify the relevant molecular mechanisms. PKM2 expression was significantly up-regulated in both mouse and human fibrotic livers compared with normal livers, and mainly detected in activated, rather than quiescent, HSCs. PKM2 knockdown markedly inhibited the activation and proliferation of HSCs in vitro. Interestingly, the PKM2 dimer, rather than the tetramer, induced HSC activation. PKM2 tetramerization induced by TEPP-46 effectively inhibited HSC activation, reduced aerobic glycolysis, and decreased MYC and CCND1 expression via regulating histone H3K9 acetylation in activated HSCs. TEPP-46 and shikonin dramatically attenuated liver fibrosis in vivo. Our findings demonstrate a nonmetabolic role of PKM2 in liver fibrosis. PKM2 tetramerization or suppression could prevent HSC activation and protects against liver fibrosis.


Assuntos
Células Estreladas do Fígado/enzimologia , Cirrose Hepática/enzimologia , Multimerização Proteica , Piruvato Quinase/metabolismo , Acetilação , Animais , Ciclina D1/metabolismo , Feminino , Células Estreladas do Fígado/patologia , Histonas/metabolismo , Humanos , Cirrose Hepática/patologia , Masculino , Camundongos , Compostos Orgânicos/farmacologia , Proteínas Proto-Oncogênicas c-myc/metabolismo
13.
Aging (Albany NY) ; 12(14): 13895-13904, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32721928

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a novel infectious disease that may cause fever, dry cough, fatigue and shortness of breath. The impact of COVID-19 on liver function is not well described. RESULTS: We found that the overall frequency of LFT abnormality was 17.6%. Frequency of LFT abnormality was significantly greater in patients with severe/critical (SC) COVID-19 compared to those with mild/moderate (MM) COVID-19 (32.4% vs 11.6%, p=0.011). Among patients with LFT abnormality, the median age was significantly higher in the SC group compared to the MM group (52 vs 39 years, p=0.021). CONCLUSION: COVID-19 is frequently associated with mild liver function abnormality, particularly in individuals with severe/critical COVID-19 who were older. Liver function should be monitored carefully during infection, with judicious use of hepatotoxic agents where possible and avoidance of prolonged hypotension to minimize liver injury in older patients. METHODS: The No. 2 People's Hospital of Fuyang City in China has admitted a total of 159 patients with confirmed COVID-19 since the outbreak from January 2020 to March 2020. We analyzed the incidence of liver function test (LFT) abnormality in these patients with confirmed COVID-19 infection.


Assuntos
Infecções por Coronavirus/complicações , Hepatopatias/virologia , Pneumonia Viral/complicações , Adulto , Fatores Etários , Idoso , Betacoronavirus , China/epidemiologia , Feminino , Humanos , Incidência , Hepatopatias/epidemiologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Pandemias
14.
Exp Mol Med ; 52(7): 1062-1074, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32632241

RESUMO

Dexmedetomidine (DEX) is an anesthetic that is widely used in the clinic, and it has been reported to exhibit paradoxical effects in the progression of multiple solid tumors. In this study, we sought to explore the mechanism by which DEX regulates hepatocellular carcinoma (HCC) progression underlying liver fibrosis. We determined the effects of DEX on tumor progression in an orthotopic HCC mouse model of fibrotic liver. A coculture system and a subcutaneous xenograft model involving coimplantation of mouse hepatoma cells (H22) and primary activated hepatic stellate cells (aHSCs) were used to study the effects of DEX on HCC progression. We found that in the preclinical mouse model of liver fibrosis, DEX treatment significantly shortened median survival time and promoted tumor growth, intrahepatic metastasis and pulmonary metastasis. The DEX receptor (ADRA2A) was mainly expressed in aHSCs but was barely detected in HCC cells. DEX dramatically reinforced HCC malignant behaviors in the presence of aHSCs in both the coculture system and the coimplantation mouse model, but DEX alone exerted no significant effects on the malignancy of HCC. Mechanistically, DEX induced IL-6 secretion from aHSCs and promoted HCC progression via STAT3 activation. Our findings provide evidence that the clinical application of DEX may cause undesirable side effects in HCC patients with liver fibrosis.

15.
Cancer Manag Res ; 12: 2369-2379, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32308477

RESUMO

Objective: To assess the clinical value of the PCR-reverse dot blot human papillomavirus genotyping test during follow-up of patients with CIN grade 2 or worse (CIN 2+). Methods: Four hundred patients with CIN 2+ receiving treatment from January 2008 to January 2017 were included in our study. Postoperative follow-up procedures comprised HPV examination and cervical cytology every 3-6 months for the first 2 years and then followed up every 6-12 months. A pathology examination was performed when there was a positive funding for HPV 16/18 or an abnormal ThinPrep cytology test (TCT) with or without positive for HR-HPV according to the American Society for Coloscopy and Cervical Pathology (ASCCP) guidelines. Results: The median follow-up period was 27.10±12.47 months (ranging from 3 to 50 months). During follow-up, 12.00% (48/400) of the women developed residual/recurrent disease. The highest risk in CIN 2+ and CIN 3+ residual/recurrence was HPV-16/-18 (hazard ratio (HR)=12.898, 95% CI= 6.849-24.289; HR= 20.726, 95% CI= 9.64-44.562, respectively). Among the different follow-up methods, type-specific (TP) HR-HPV persistent infection showed the highest cumulative incidence risk (CIR) (84.62%, 95% CI=73.29-95.94) and HR (5.38, 95% CI= 2.596-11.149) during the 4-year follow-up period. At the CIN 2+ and CIN 3+ endpoints, TP-HPV testing had relatively high sensitivity (84.62%, 95% CI=73.29-95.94 and 89.28%, 95% CI= 77.83-100.00, respectively) and specificity (78.07%, 95% CI= 72.70-83.44 and 75.73%, 95% CI= 70.30-81.17, respectively). However, at the CIN 2+/CIN 3+ endpoint, TCT follow-up had a sensitivity of 60.42%/62.16% (95% CI=46.58-72.25/46.54-77.79) and specificity of 90.18%/88.72% (95% CI=86.95-93.41/85.35-92.10). Conclusion: TP HR-HPV follow-up can provide a reliable and sensitive clinical reference for CIN 2+ postoperative patients.

16.
Viruses ; 12(4)2020 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-32276512

RESUMO

BACKGROUND: 2', 5'-oligoadenylate synthetase 2 (OAS2) has been known as an antiviral interferon-stimulated gene (ISG). However, the role of OAS2 on Zika virus (ZIKV) replication is still unknown. In this study, we sought to explore the effect of OAS2 on ZIKV replication and its underlying mechanism. METHODS: We performed RNA-Seq in A549 cells with or without ZIKV infection. OAS2 or RIG-I was overexpressed by plasmid transfection or knocked down by siRNA in A549 cells. Expression levels of mRNA and protein of selected genes were detected by RT-qPCR and Western Blot, respectively. Interferon stimulated response element (ISRE) activity was examined by dual luciferase assay. RESULTS: We found that ZIKV infection induced OAS2 expression through a RIG-I-dependent pathway. OAS2 overexpression inhibited ZIKV replication, while OAS2 knockdown increased ZIKV replication. We observed that OAS2 inhibited ZIKV replication through enhanced IFNß expression, leading to the activation of the Jak/STAT signaling pathway. CONCLUSION: ZIKV infection induced OAS2 expression, which in turn exerted its anti-ZIKV activities through the IFN-activated Jak/STAT signaling pathway.

17.
Med Oncol ; 37(5): 37, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32232578

RESUMO

The relationship between high-risk-human-papillomavirus (HR-HPV) viral loads and residual/recurrence lesion is uncertain. This study aimed to evaluate the clinical value of HR-HPV viral loads to predict the residual/recurrence lesions among women with high-grade squamous lesions or worse (≥ HSIL) after surgery. Finally, 301 women who underwent primary screening of cervical cancer using polymerase-chain-reaction-(PCR)-reverse-dot-blot-(RDB) human papillomavirus (HPV) genotyping and cytology assays were enrolled. They received surgery and took HR-HPV viral loads with a BioPerfectus Multiplex Real-Time PCR assay. Colposcopy biopsies were performed in patients with HPV-16/18(+) and/or TCT ≥ ASCUS with HR-HPV(+). The risk of HR-HPV viral loads and potentials factors for residual/recurrence lesions were analyzed and the optimal cut-off values of HR-HPV viral loads were calculated. The significant differences were found in residual/recurrence lesions among patients with different ages, margin status, cytology and HR-HPV at 6 months (all P < 0.05). Interestingly, HPV viral loads were observed significant differences in the group of residual lesions, not recurrence group. Furthermore, except for HPV-31/33, the viral loads of HP-16/52/58 were significant differences in residual lesions. The cut-off level of HR-HPV viral loads was 5.22 copies/10,000 cells, providing viable triage for the risk of residual lesions. Compared with different follow-up methods, the HR-HPV viral loads ≥ 5.22copies/10,000 cells (HR 3.39, 95% CI 1.57-7.35) had a higher risk for developing residual lesions. HR-HPV viral loads can be a reliable predictor of residual lesions. Furthermore, women with viral loads ≥ 5.22 copies/10,000 cells may have higher risk for residual disease and should be give a more aggressive treatment and follow-up strategy.


Assuntos
Neoplasia Intraepitelial Cervical/virologia , Papillomaviridae/fisiologia , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/virologia , Carga Viral , Adulto , Idoso , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasia Residual , Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/cirurgia , Estudos Prospectivos , Risco , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Adulto Jovem
18.
J Hepatol ; 73(1): 161-169, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32145257

RESUMO

BACKGROUND & AIMS: The vitronectin receptor integrin αvß3 drives fibrogenic activation of hepatic stellate cells (HSCs). Molecular imaging targeting the integrin αvß3 could provide a non-invasive method for evaluating the expression and the function of the integrin αvß3 on activated HSCs (aHSCs) in the injured liver. In this study, we sought to compare differences in the uptake of [18F]-Alfatide between normal and injured liver to evaluate its utility for assessment of hepatic fibrogenesis. METHODS: PET with [18F]-Alfatide, non-enhanced CT, histopathology, immunofluorescence staining, immunoblotting and gene analysis were performed to evaluate and quantify hepatic integrin αvß3 levels and liver fibrosis progression in mouse models of fibrosis (carbon tetrachloride [CCl4] and bile duct ligation [BDL]). The liver AUC divided by the blood AUC over 30 min was used as an integrin αvß3-PET index to quantify fibrosis progression. Ex vivo analysis of frozen liver tissue from patients with fibrosis and cirrhosis verified the animal findings. RESULTS: Fibrotic mouse livers showed enhanced [18F]-Alfatide uptake and retention compared to control livers. The radiotracer was demonstrated to bind specifically with integrin αvß3, which is mainly expressed on aHSCs. Autoradiography and histopathology confirmed the PET imaging results. Further, the mRNA and protein level of integrin αvß3 and its signaling complex were higher in CCl4 and BDL models than controls. The results obtained from analyses on human fibrotic liver sections supported the animal findings. CONCLUSIONS: Imaging hepatic integrin αvß3 with PET and [18F]-Alfatide offers a potential non-invasive method for monitoring the progression of liver fibrosis. LAY SUMMARY: Integrin αvß3 expression on activated hepatic stellate cells (aHSCs) is associated with HSC proliferation during hepatic fibrogenesis. Herein, we show that a radioactive tracer, [18F]-Alfatide, binds to integrin αvß3 with high affinity and specificity. [18F]-Alfatide could thus be used as a non-invasive imaging biomarker to track hepatic fibrosis progression.

19.
Int J Biol Sci ; 16(7): 1194-1206, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32174794

RESUMO

Metabolic reprogramming is a hallmark of cancer. Mammalian genome is characterized by pervasive transcription, generating abundant non-coding RNAs (ncRNAs). Long non-coding RNAs (lncRNAs) are freshly discovered functional ncRNAs exerting extensive regulatory impact through diverse mechanisms. Emerging studies have revealed widespread roles of lncRNAs in the regulation of various cellular activities, including metabolic pathways. In this review, we summarize the latest advances regarding the regulatory roles of lncRNAs in cancer metabolism, particularly their roles in mitochondrial function, glucose, glutamine, and lipid metabolism. Moreover, we discuss the clinical application and challenges of targeting lncRNAs in cancer metabolism. Understanding the complex and special behavior of lncRNAs will allow a better depiction of cancer metabolic networks and permit the development of lncRNA-based clinical therapies by targeting cancer metabolism.

20.
Front Immunol ; 10: 1815, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417575

RESUMO

Gonorrhea is a type III legal communicable disease caused by Neisseria gonorrhoeae (NG), one of the most common sexually transmitted bacteria worldwide. NG infection can cause urethritis or systemic inflammation and may lead to infertility or other complications. The NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is a protein complex composed of NLRP3, apoptosis-associated speck-like protein and caspase-1 and is an important part of the cellular machinery controlling the release of interleukin (IL)-1ß and IL-18 and the pathogenesis of numerous infectious diseases. It has been reported that NG infection activates the NLRP3 inflammasome; however, the underlying mechanism remain unclear. In this report, the signaling pathways involved in the regulation of NG-mediated NLRP3 inflammasome activation in macrophages were studied. The results indicated that viable NG, but not heat-killed or freeze/thaw-killed NG, activated the NLRP3 inflammasome in macrophages through toll-like receptor 2, but not toll-like receptor 4. NG infection provided the priming signal to the NLRP3 inflammasome that induced the expression of NLRP3 and IL-1ß precursor through the nuclear factor kappa B and mitogen-activated protein kinase pathways. In addition, NG infection provided the activation signal to the NLRP3 inflammasome that activated caspase-1 through P2X7 receptor-dependent potassium efflux, lysosomal acidification, mitochondrial dysfunction, and reactive oxygen species production pathways. Furthermore, we demonstrated that NLRP3 knockout increased phagocytosis of bacteria by macrophages and increases the bactericidal activity of macrophages against NG. These findings provide potential molecular targets for the development of anti-inflammatory drugs that could ameliorate NG-mediated inflammation.


Assuntos
Gonorreia , Inflamassomos/imunologia , Ativação de Macrófagos , Macrófagos , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Neisseria gonorrhoeae/imunologia , Animais , Gonorreia/imunologia , Gonorreia/patologia , Humanos , Macrófagos/imunologia , Macrófagos/microbiologia , Macrófagos/patologia , Camundongos , Células THP-1
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