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1.
Xenobiotica ; : 1-40, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32400275

RESUMO

First dose prediction is challenging in neonates. Our objective in this proof-of-concept study was to perform a pharmacokinetic (PK) bridging study from juvenile mice to neonates for drugs metabolized by CYP3A.We selected midazolam and clindamycin as model drugs. We developed juvenile mice population PK models using NONMEM. The PK parameters of these two drugs in juvenile mice were used to bridge PK parameters in neonates using different correction methods. The bridging results were evaluated by the fold-error of 0.5- to 1.5-folds.Simple allometry with and without a correction factor for maximum lifespan potential could be used for a bridging of clearance (CL) and volume of distribution (Vd), respectively, from juvenile mice to neonates. Simulation results demonstrated that for midazolam, 100% of clinical studies for which both the predictive CL and Vd were within 0.5- to 1.5-folds of the observed. For clindamycin, 75% and 100% of clinical studies for which the predictive CL and Vd were within 0.5- to 1.5-folds of the observed.A PK bridging of drugs metabolized by CYP3A is feasible from juvenile mice to neonates. It could be a complement to the ADE and PBPK models to support the first dose in neonates.

2.
Opt Lett ; 45(9): 2684-2687, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32356847

RESUMO

We propose a precise diamond micromachining method based on ultraviolet femtosecond laser direct writing and a mixed acid heating chemical treatment. The chemical composition of the attached clusters generated during laser ablation and their effects on morphologies were investigated in experiments. The averaged roughness of pristine and processed regions reduced to 0.64 nm and 9.4 nm from 20.5 nm and 37.4 nm, respectively. With this method, spiral zone plates (SZPs) were inscribed on a high-pressure high-temperature diamond surface as micro-optical vortex generators. The optical performances of the diamond SZPs were characterized in both experiments and simulations, which were very consistent with each other. This chemical auxiliary processing method will contribute greatly to the wide application of integration and miniaturization of diamond surface optical components.

3.
Virus Res ; : 198019, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32417180

RESUMO

Rhabdoviruses cause devastating diseases in aquaculture, resulting in enormous economic losses. Our previous studies indicated that imidazole arctigenin derivatives possessed antiviral activities against aquatic rhabdoviruses. Based on the data of structure-activity relationship, a new imidazole arctigenin derivative, 4-(8-(2-bromoimidazole)octyloxy)-arctigenin (BOA), was designed and synthesized. And its antiviral activities against aquatic rhabdoviruses (SVCV, IHNV and MSRV) were evaluated in vitro. By comparing inhibitory concentration at half-maximal activity (IC 50), we found that BOA (IC50 = 1.11 µM) possessed a higher anti-IHNV activity than the antiviral imidazole arctigenin derivatives which were found in our previous study. Besides, BOA could cause profound inhibition of SVCV and MSRV replication. By the reduction assays on cytopathic effect, BOA exhibited a protective effect on two host cell lines. As a typical rhabdovirus, SVCV was chosen as a model to illuminate the anti-rhabdovirus mechanism of BOA. BOA was discovered to not impact directly on viral particles or interfere with SVCV adsorption. And it worked within the 2-6 h of the early phase of virus replication. In addition, after repression of cell cycle S phase and recovery of caspase-3/8/9 activities activated by SVCV, BOA inhibited SVCV-induced apoptosis and then reduced the release of viral particles at the late stage of virus replication. Altogether, BOA was expected to be a highly efficient antiviral agent against multiple rhabdoviruses in the field of aquaculture.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32419443

RESUMO

Developing scalable and robust processing methods with low material waste remains a challenge for organic solar cells (OSCs) to become a practical renewable energy source. Here we present a novel low-cost processing approach termed as Soft Porous Blade Printing (SPBP), which uses a layer of soft porous material such as filter paper as the printing blade. The inherent porous microstructure of the blade offers high shear rates that facilitate the alignment, crystallization and orientation of active materials during printing. Moreover, SPBP relaxes the stringent requirement of gap control and enables continuous ink delivery for uninterrupted film fabrication with adjustable thickness. Higher photovoltaic performances are achieved in the SPBP printed OSCs than that of the spin-coated counterparts for two non-fullerene-acceptor active-layer systems (Y6:PM6 and PTQ10:IDIC). Y6:PM6 cells printed by SPBP without any additive exhibit power conversion efficiencies up to 14.75%, which is among the highest reported to date for non-spin-coated OSCs.

5.
Int Heart J ; 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32418972

RESUMO

Resistin is an adipocytokine that is abundantly secreted from lipid cells and is related to the inflammatory process and cardiometabolic diseases. This study aimed to examine the role of resistin on inflammation and its effect on the clinical outcome of patients with atrial fibrillation (AF) following catheter ablation.A total of 108 patients (56.9 ± 12.0 years, 76.8% male) with symptomatic and drug-refractory AF undergoing catheter ablation were enrolled. Inflammatory biomarkers and epicardial fat volume by contrast computed tomography (CT) images were assessed in all patients before the procedure. Baseline resistin correlated with epicardial fat volume, tumor necrosis factor-α (TNF-α), and left atrial (LA) scar area. After the index procedure, the univariate analysis revealed that hypertension, persistent AF, LA diameter, and plasma resistin level were related to recurrent atrial arrhythmia. Multivariate regression analysis revealed that persistent AF, LA diameter, and plasma resistin level all independently predicted recurrent atrial arrhythmia after ablation. Plasma resistin with a level higher than 777 (pg/mL) could predict recurrence following catheter ablation of AF.High plasma resistin level is associated with poor left atrial substrate, high epicardial fat volume, and elevated TNF-α level in patients with AF. Plasma resistin may predict the recurrence of atrial arrhythmia after ablation.

6.
Clin Chim Acta ; 508: 1-8, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32387092

RESUMO

BACKGROUND: This study aimed to investigate the role of anti-CFH autoantibodies in lupus nephritis based on a well-defined cohort. METHODS: One hundred twenty patients with biopsy-proven active lupus nephritis were collected as the discovery cohort, sixty patients served as the validation cohort, thirty-four patients with SLE without renal involvement (NR-SLE) were as disease controls, and thirty healthy donors were also included. The anti-CFH autoantibodies and IgG subclasses were detected by ELISA, and epitopes were evaluated by western blot. Anti-CFH autoantibodies were purified by affinity chromatography column, and the interference on the biofunctions of CFH was further studied by the C3b binding assay and cofactor activity assay in vitro. RESULTS: The prevalence of anti-CFH autoantibodies in lupus nephritis was significantly higher than that in healthy controls (8.3% (10/120) vs. 0% (0/30), P = 0.017), and no significant difference was found between the discovery and the validation group (8.3% (10/120) vs. 11.7% (7/60), P = 0.268) or the discovery and the NR-SLE group (8.3% (10/120) vs. 11.8% (4/34), P = 0.231). The subclass was mainly IgG2 (7/10), and major epitopes were in the middle (8/10 in SCRs 11-14) and N-terminal (7/10 in SCRs 1-4) regions of CFH. Patients with anti-CFH autoantibodies had a significantly lower prevalence of acute kidney injury (0% (0/10) vs. 40.0%(4/10), P = 0.025), lower serum creatinine levels (0.76 (0.40, 1.06) vs. 1.43 (0.46, 11.15), mg/dL, P = 0.023), and higher hemoglobin levels (113.8 ± 24.63 vs. 90.0 ± 22.53, g/L, P = 0.037) than those who were negative after further stratified analysis. A functional study showed that anti-CFH autoantibodies purified from patients with lupus nephritis could improve the binding between CFH and C3b, and also enhance the cofactor activity of CFH in vitro. CONCLUSIONS: Anti-CFH autoantibodies were detected in patients with lupus nephritis in approximately 10% of patients with polyepitopes and IgG2 subclass predominance. Patients with anti-CFH autoantibodies presented with milder renal damage, and the purified autoantibodies could enhance the C3b binding and CFI cofactor activity of CFH in vitro, which suggested a protective role in the lupus nephritis.

7.
Mil Med Res ; 7(1): 24, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32393381

RESUMO

BACKGROUND: Many healthcare workers were infected by coronavirus disease 2019 (COVID-19) early in the epidemic posing a big challenge for epidemic control. Hence, this study aims to explore perceived infection routes, influencing factors, psychosocial changes, and management procedures for COVID-19 infected healthcare workers. METHODS: This is a cross-sectional, single hospital-based study. We recruited all 105 confirmed COVID-19 healthcare workers in the Zhongnan Hospital of Wuhan University from February 15 to 29, 2020. All participants completed a validated questionnaire. Electronic consent was obtained from all participants. Perceived causes of infection, infection prevention, control knowledge and behaviour, psychological changes, symptoms and treatment were measured. RESULTS: Finally, 103 professional staff with COVID-19 finished the questionnaire and was included (response rate: 98.1%). Of them, 87 cases (84.5%) thought they were infected in working environment in hospital, one (1.0%) thought their infection was due to the laboratory environment, and 5 (4.9%) thought they were infected in daily life or community environment. Swab of throat collection and physical examination were the procedures perceived as most likely causing their infection by nurses and doctors respectively. Forty-three (41.8%) thought their infection was related to protective equipment, utilization of common equipment (masks and gloves). The top three first symptoms displayed before diagnosis were fever (41.8%), lethargy (33.0%) and muscle aches (30.1%). After diagnosis, 88.3% staff experienced psychological stress or emotional changes during their isolation period, only 11.7% had almost no emotional changes. Arbidol (Umifenovir; an anti-influza drug; 69.2%) was the drug most commonly used to target infection in mild and moderate symptoms. CONCLUSION: The main perceived mode of transmission was not maintaining protection when working at a close distance and having intimate contact with infected cases. Positive psychological intervention is necessary.


Assuntos
Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/psicologia , Infecções por Coronavirus/transmissão , Pessoal de Saúde/psicologia , Controle de Infecções/métodos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/psicologia , Pneumonia Viral/transmissão , Adulto , Betacoronavirus , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional , Equipamento de Proteção Individual , Estresse Psicológico , Inquéritos e Questionários , Centros de Atenção Terciária , Adulto Jovem
8.
Oncology ; : 1-9, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32408308

RESUMO

BACKGROUND/AIM: A great proportion of patients with rectal cancer initially present with locally advanced disease and can potentially benefit from neoadjuvant concurrent chemoradiotherapy (CCRT) for downstaging before surgery. However, risk and clinical outcome stratification remain a great challenge. We aimed to find the potential biomarker to predict the effect of neoadjuvant CCRT on rectal cancer. METHODS: We identified epiregulin (EREG) as the most significant predictive marker for neoadjuvant CCRT response from the published rectal cancer transcriptome data set GSE35452. We collected 172 biopsy specimens from rectal cancer patients who received neoadjuvant CCRT followed by radical proctectomy, performed EREG immunohistochemistry, and analyzed the H-scores. We further examined the correlations between the expression level of EREG and clinicopathological features, tumor regression grade, and survival, including disease-specific survival (DSS), locoregional recurrence-free survival (LRFS), and metastasis-free survival (MeFS). RESULTS: High EREG expression was significantly related to early pretreatment (pre-Tx) and posttreatment (post-Tx) tumor status (T1, T2, p = 0.047 and p < 0.001), pre-Tx and post-Tx negative nodal status (N0, p < 0.001 and p = 0.004), less vascular and perineurial invasion (p = 0.015 and p = 0.023), and higher tumor regression grade (p < 0.001). In the survival analysis, high EREG expression was significantly associated with better DSS (p < 0.0001), LRFS (p = 0.0004), and MeFS (p < 0.0001). In the multivariate analysis, high EREG expression remained prognostically significant for better DSS (p = 0.003; hazard ratio: 5.599). CONCLUSION: These data suggest that EREG is a potential predictive marker and therapeutic target in rectal cancer patients receiving neoadjuvant CCRT.

9.
G3 (Bethesda) ; 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32358017

RESUMO

Salmonella are a type of bacteria known to cause food-borne illness. Their host range varies widely, and their susceptibility to the host determines its pathogenicity. Salmonella enterica serovar Rissen (S. Rissen) is a widely distributed serotype; however, its virulence and pathogenicity are poorly understood. In this study, the pathogenicity and antibiotic resistance of a representative S Rissen isolate were investigated. The cell model results showed that S. Rissen preferred to replicate in human macrophage cells U937 compared to murine macrophage cells RAW264.7, suggesting that it has a level of host adaptability. Genome sequencing and comparison analysis revealed that the distribution and nonsynonymous single nucleotide polymorphisms of virulence factors in S. Rissen were similar to those in S Typhi rather than to those in S. Typhimurium. Taken together, our results suggest that although S Rissen is a common serotype distributed in swine herds, pork and chicken products, it has strong ability to infect humans.

10.
Dalton Trans ; 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32363368

RESUMO

Designing low-cost and high-performance bifunctional electrocatalysts towards hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is vitally important for water splitting. Herein, we synthesize Co2-xNixO2 (0 < x < 1.0) hexagonal nanosheets with different Co/Ni molar ratios via a facile coprecipitation process followed by calcination under an Ar atmosphere. Changing the Co/Ni molar ratios of the Co2-xNixO2 products is found to have a momentous influence on the microstructures, specific surface areas and electrocatalytic performances. At a Co/Ni molar ratio of 0.6, the Co1.4Ni0.6O2 nanosheet exhibits the largest specific surface area of 60.63 m2 g-1, the best OER with an onset overpotential of 278.5 mV, and HER of 72.8 mV as a bifunctional electrocatalyst. Meanwhile, the minimum Tafel slope is 113.6 mV dec-1 for OER and 77.4 mV dec-1 for HER. The Co1.4Ni0.6O2 nanosheet has excellent OER and HER activity at 0.1 mg cm-2 trace loading. Moreover, we construct an overall water splitting cell using the Co1.4Ni0.6O2 bifunctional electrocatalyst in a two-electrode system to further demonstrate the practical application, which needs a cell voltage of 1.75 V at a current density of 10 mA cm-2 and exhibits great long-term stability. These results provide an efficient strategy for the rational design of Co-based oxides towards bifunctional overall water electrocatalysts.

11.
Zhongguo Gu Shang ; 33(4): 332-6, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32351087

RESUMO

OBJECTIVE: To explore the clinical effect of bridging system in the treatment of severe comminuted femoral fracture. METHODS: From March 2016 to October 2018, 50 patients with severe comminuted femoral fracture including 35 males and 15 females, aged 48 to 72(54.6±8.7) years, were admitted. All cases were comminuted fractures of the femoral shaft, 16 with proximal femur fractures and 7 with distal femur fractures. All cases were all unilateral fractures, 23 on the left and 27 on the right. The time from injury to operation was 5 to 60 (26.7±13.3) hours. The cause of injury was traffic accident, 12 cases with high fall, 35 cases fell and 3 cases fell accidentally. The patients were treated with bridge combined internal fixation system, and the operative effect and fracture healing were analyzed. RESULTS: The operation was successful in all patients. There was no change to other fixed operation. The operation time was (75.8±12.3) min, the amount of bleeding was(356.4±64.8) ml, and there was no serious postoperative complications such as infection, internal fixation displacement, re fracture and nonunion. After 6 to 36 months follow-up, the fracture healing was evaluated by Warden's score. With the extension of observation time, Warden's score gradually increased, and the time of bone healing was(5.5±0.9) months. Harris score and HSS score were used to evaluate the function of hip and knee joint respectively. With the extension of time, Harris score and HSS score increased gradually. Six months after operation, Harris score was 83.5±11.2, HSS score was 79.7±10.5. During the follow-up period, there were no serious complications such as internal fixation displacement, re-fracture, nonunion of fracture and deep vein thrombosis of lower extremity. CONCLUSION: The bridge combined internalfixation system has better safety and effectiveness in the treatment of severe comminuted femoral fracture. As long as the requirements of local anatomy and biomechanics are strictly mastered and the operation risks are fully evaluated in combination with imaging, the better fixation effect can be achieved. The operation has less trauma, fewer complications and simple operation, which is believed to have a wider application potential. Due to the limited sample size and follow-up time, no clinical control was set up, the results of the study still need to be further verified by prospective trials.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32365254

RESUMO

We have developed an unprecedented Pd-catalyzed formal hydroalkylation of alkynes with hydrazones, which are generated in situ from naturally abundant aldehydes, as both alkylation reagents and hydrogen donors. The hydroalkylation proceeds with high regio- and stereoselectivity to form (Z)-alkenes, which are more difficult to generate, instead of (E)-alkenes. The reaction is compatible with a wide range of functional groups, including hydroxyl, ester, ketone, nitrile, boronic ester, amine and halide. Furthermore, late-stage modifications of natural products and pharmaceutical derivatives exemplify its unique chemoselectivity, regioselectivity and synthetic applicability. The mechanistic studies indicate the possible involvement of palladium-hydride intermediates.

13.
Am J Nephrol ; : 1-10, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32320985

RESUMO

BACKGROUND: A revision of the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification for lupus nephritis has been published in 2018. The current study aimed to verify the utility of this system. MATERIALS AND METHODS: A total of 101 lupus nephritis patients from a large Chinese cohort who underwent renal biopsy in Peking University First Hospital were reevaluated by 2 renal pathologists, who had no knowledge of the clinical findings. The association between clinical data at the time of initial renal biopsy and follow-up and pathological features were further analyzed on all patients selected. RESULTS: The mean age of the cohort was 33 years with a male/female ratio of 1:9, and a median follow-up period of 128 months. The presence and extent of mesangial hypercellularity, endocapillary hypercellularity, global and segmental glomerulosclerosis, neutrophil exudation/karyorrhexis, glomerular hyaline deposits, extracapillary proliferation (crescents), tubular atrophy/interstitial fibrosis, and interstitial inflammation were significantly correlated with several clinical renal injury indices (systemic lupus erythematosus disease activity index, serum creatinine value, proteinuria, and C3 level) at the time of biopsy. By multivariable Cox hazard analysis, fibrous crescents, tubular atrophy/interstitial fibrosis, and the modified National Institutes of Health chronicity index were independent risk factors for patients' composite renal outcomes (hazard ratio [HR] 4.100 [95% CI 1.544-10.890], p = 0.005; HR 8.584 [95% CI 2.509-29.367], p = 0.001; and HR 3.218 [95% CI 1.138-9.099], p = 0.028; respectively). CONCLUSIONS: The 2018 revision of the ISN/RPS classification for lupus nephritis has utility for prediction of clinical renal outcomes.

14.
Pathol Res Pract ; 216(5): 152922, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32249003

RESUMO

OBJECTIVE: Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is now the standard care for patients with advanced rectal cancer. Because a certain proportion of these patients have poor response to CCRT, the risk stratification of survival outcomes needs to be investigated. DNA repair responses in tumor cells can regulate malignant potential and therapy resistance. In this study, we analyzed the clinical significance of principal DNA repair effectors in patients with rectal cancer. METHODS: We applied data mining for DNA repair pathways in a published transcriptome for rectal cancer cases, and identified that tumors with BRCA2 downregulation correlated with poor response to CCRT. We next examined BRCA2 expression by using immunohistochemistry staining in tumor tissues of 172 patients with rectal cancer. The correlation between BRCA2 expression levels and clinical variables was further analyzed in this rectal cancer cohort. RESULTS: Among clinical and pathological factors, low BRCA2-expression was significantly correlated with higher pre-treatment (Tx) tumor status (P = .013), post-Tx tumor (P < .001) and nodal status (P = .044), vascular invasion (P = .008), and poor tumor regression grades (P < .001). In analyses of survival outcomes, patients with low BRCA2-expression were associated with shorter local recurrence-free survival (LRFS; P = .0005) and disease-specific survival (P = .0269). Multivariate analyses confirmed the independent prognostic value of low BRCA2-expression for shorter LRFS (P = .045, hazard ratio = 4.695). CONCLUSION: Low BRCA2-expression is a significant predictor for tumors in advanced stages, poor response to CCRT, and shorter survivals in patients with rectal cancer. Poly (adenosine diphosphate-ribose) polymerase inhibitors targeting DNA repair response in cells have demonstrated clinical efficacy in BRCA2-mutated patients with cancer. Further studies evaluating the efficacy of CCRT combined with these inhibitors in low BRCA2-expressing rectal cancers are encouraged.

15.
BMC Cancer ; 20(1): 303, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293362

RESUMO

BACKGROUND: Neoadjuvant therapy plus oesophagectomy has been accepted as the standard treatment for patients with potentially curable locally advanced oesophageal cancer. No completed randomized controlled trial (RCT) has directly compared neoadjuvant chemotherapy and neoadjuvant chemoradiation in patients with oesophageal squamous cell carcinoma (ESCC). The aim of the current RCT is to investigate the impact of neoadjuvant chemotherapy plus surgery and neoadjuvant chemoradiotherapy plus surgery on overall survival for patients with resectable locally advanced ESCC. METHODS: This open label, single-centre, phase III RCT randomized patients (cT2-T4aN + M0 and cT3-4aN0M0) in a 1:1 fashion to receive either the CROSS regimen (paclitaxel 50 mg/m2; carboplatin (area under the curve = 2), q1w, 5 cycles; and concurrent radiotherapy, 41.4 Gy/23 F, over 5 weeks) or neoadjuvant chemotherapy (paclitaxel 175 mg/m2; and cisplatin 75 mg/m2, q21d, 2 cycles). Assuming a 12% 5-year overall survival difference in favour of the CROSS regimen, 80% power with a two-sided alpha level of 0.05 and a 5% dropout each year for an estimated 3 years enrolment, the power calculation requires 456 patients to be recruited (228 in each group). The primary endpoint is 5-year overall survival, with a minimum 5-year follow-up. The secondary endpoints include 5-year disease-free survival, toxicity, pathological complete response rate, postoperative complications, postoperative mortality and quality of life. A biobank of pre-treatment and resected tumour tissue will be built for translational research in the future. DISCUSSION: This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies. TRIAL REGISTRATION: NCT04138212, date of registration: October 24, 2019.

16.
Sheng Li Xue Bao ; 72(2): 175-180, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32328611

RESUMO

The present study was aimed to clarify the signaling molecular mechanism by which fibroblast growth factor 21 (FGF21) regulates leptin gene expression in adipocytes. Differentiated 3T3-F442A adipocytes were used as study object. The mRNA expression level of leptin was detected by fluorescence quantitative RT-PCR. The phosphorylation levels of proteins of signal transduction pathways were detected by Western blot. The results showed that FGF21 significantly down-regulated the mRNA expression level of leptin in adipocytes, and FGF21 receptor inhibitor BGJ-398 could completely block this effect. FGF21 up-regulated the phosphorylation levels of ERK1/2 and AMPK in adipocytes. Either ERK1/2 inhibitor SCH772984 or AMPK inhibitor Compound C could partially block the inhibitory effect of FGF21, and the combined application of these two inhibitors completely blocked the effect of FGF21. Neither PI3K inhibitor LY294002 nor Akt inhibitor AZD5363 affected the inhibitory effect of FGF21 on leptin gene expression. These results suggest that FGF21 may inhibit leptin gene expression by activating ERK1/2 and AMPK signaling pathways in adipocytes.

17.
Int J Oncol ; 57(1): 139-150, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32319597

RESUMO

Prostate cancer (PCa) is the second leading cause of cancer­related death among men worldwide. The present study aimed to investigate the role of germ cell­specific gene 2 protein (GSG2), also termed histone H3 phosphorylated by GSG2 at threonine­3, in the development and progression of PCa. GSG2 expression levels in PCa tissues and para­carcinoma tissues was detected by immunohistochemistry. The GSG2 knockdown cell model was constructed by lentivirus infection, and the knockdown efficiency was verified by qPCR and WB. In addition, the effects of shGSG2 on cell proliferation, colony formation and apoptosis were evaluated by Celigo cell counting assay, Giemsa staining and flow cytometry, respectively. Tumor development in nude mice was also detected. GSG2 expression was upregulated in PCa tissues and human PCa cell lines PC­3 and DU 145. High expression of GSG2 in tumor samples was associated with progressed tumors. GSG2 knockdown suppressed cell proliferation and colony formation, but promoted apoptosis, which was also verified in vivo. The results of the present study revealed that GSG2 upregulation was associated with PCa progression; GSG2 knockdown inhibited cell proliferation and colony formation and induced apoptosis, and may therefore serve as a potential therapeutic target for PCa therapy.

18.
Mol Immunol ; 122: 69-79, 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32305690

RESUMO

Recent studies have shown that aberrant activation of the complement system plays an important role in the pathogenesis of preeclampsia. There is evidence to suggest that aberrant activation of the complement system may already be present during the first trimester. Here, we performed a prospective study in which peripheral blood samples were collected from 500 women during pregnancy. Twenty-one patients (41 specimens) suffering from preeclampsia later in pregnancy were classified into the study group, and sixty-three gravidas with normal pregnancies (136 specimens) were selected as the control group. The plasma concentrations of complement factor B (CFB), C1q, complement factor H (CFH), C3c, C4, C3a, C5a and soluble C5b-9 (sC5b-9) were measured. The levels of CFB (P = 0.004), CFH (P = 0.002), C1q (P = 0.044), C3c (P = 0.032) and C4 (P = 0.015) were significantly higher in preeclampsia than in normal pregnancy during the first trimester, and these levels became similar to those in normal pregnancy thereafter. Before the onset of preeclampsia, the levels of C3a, C5a and sC5b-9 in the preeclampsia group were similar to those in control group even in late pregnancy. C3a levels showed a significant positive correlation with C5a in normal pregnancy (r=0.658, P<0.01) but not in preeclampsia (r = 0.001, P = 1).Thus, we found that aberrant activation of the complement system in patients with preeclampsia was initiated during the first trimester but returned to normal pregnancy levels in the second trimester. At the same time, there is aberrant regulation of complement activation at the C3a-C5a level in preeclampsia during pregnancy.

19.
J Immunol ; 204(10): 2627-2640, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32238460

RESUMO

Lupus nephritis (LN) is a major contributor to morbidity and mortality in lupus patients, but the mechanisms of kidney damage remain unclear. In this study, we introduce, to our knowledge, novel models of LN designed to resemble the polygenic nature of human lupus by embodying three key genetic alterations: the Sle1 interval leading to anti-chromatin autoantibodies; Mfge8-/- , leading to defective clearance of apoptotic cells; and either C1q-/- or C3-/- , leading to low complement levels. We report that proliferative glomerulonephritis arose only in the presence of all three abnormalities (i.e., in Sle1.Mfge8 -/- C1q -/- and Sle1.Mfge8 -/- C3 -/- triple-mutant [TM] strains [C1q -/-TM and C3-/- TM, respectively]), with structural kidney changes resembling those in LN patients. Unexpectedly, both TM strains had significant increases in autoantibody titers, Ag spread, and IgG deposition in the kidneys. Despite the early complement component deficiencies, we observed assembly of the pathogenic terminal complement membrane attack complex in both TM strains. In C1q-/- TM mice, colocalization of MASP-2 and C3 in both the glomeruli and tubules indicated that the lectin pathway likely contributed to complement activation and tissue injury in this strain. Interestingly, enhanced thrombin activation in C3-/- TM mice and reduction of kidney injury following attenuation of thrombin generation by argatroban in a serum-transfer nephrotoxic model identified thrombin as a surrogate pathway for complement activation in C3-deficient mice. These novel mouse models of human lupus inform the requirements for nephritis and provide targets for intervention.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32227530

RESUMO

INTRODUCTION: Accurate identification of slow conducting regions in patients with scar-related atrial tachycardia (AT) is difficult using conventional electrogram annotation for cardiac electroanatomic mapping (EAM). Estimating delays between neighboring mapping sites is a potential option for activation map computation. We describe our initial experience with CARTO 3 Coherent Mapping (Biosense Webster Inc,) in the ablation of complex ATs. METHODS: Twenty patients (58 ± 10 y/o, 15 males) with complex ATs were included. We created three-dimensional EAMs using CARTO 3 system with CONFIDENSE and a high-resolution mapping catheter (Biosense Webster Inc). Local activation time and coherent maps were used to aid in the identification of conduction isthmus (CI) and focal origin sites. System-defined slow or nonconducting zones and CI, defined by concealed entrainment (postpacing interval < 20 ms), CV < 0.3 m/s and local fractionated electrograms were evaluated. RESULTS: Twenty-six complex ATs were mapped (mean: 1.3 ± 0.7 maps/pt; 4 focal, 22 isthmus-dependent). Coherent mapping was better in identifying CI/breakout sites where ablation terminated the tachycardia (96.2% vs 69.2%; P = .010) and identified significantly more CI (mean/chamber 2.0 ± 1.1 vs 1.0 ± 0.7; P < .001) with narrower width (19.8 ± 10.5 vs 43.0 ± 23.9 mm; P < .001) than conventional mapping. Ablation at origin and CI sites was successful in 25 (96.2%) with long-term recurrence in 25%. CONCLUSIONS: Coherent mapping with conduction velocity vectors derived from adjacent mapping sites significantly improved the identification of CI sites in scar-related ATs with isthmus-dependent re-entry better than conventional mapping. It may be used in conjunction with conventional mapping strategies to facilitate recognition of slow conduction areas and critical sites that are important targets of ablation.

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