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1.
J Transl Med ; 18(1): 376, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023595

RESUMO

BACKGROUND: Monoclonal antibodies (mAbs) have been used for cancer therapy. They are large and have some disadvantages limiting their use. Smaller antibody fragments are needed as their alternatives. A fully human single-domain antibody (sdAb) has a small size of only 15 kDa and consists of only the variable domain of the human antibody heavy chain (VH). It has no immunogenicity. It can easily penetrate into tumor tissues, target an epitope inaccessible to mAb and be manufactured in bacteria for a low cost. Epidermal growth factor receptor (EGFR) is over-expressed in many cancer cells and is a good target for cancer therapy. METHODS: The EGFR protein fragment located on the EGFR extracellular domain III was chosen to screen a human sdAb library. Five human anti-EGFR sdAbs were identified. Their specific binding to EGFR was confirmed by ELISA, Western blotting and flow cytometry. Their anti-tumor effects were tested. RESULTS: Five novel fully human anti-EGFR sdAbs were isolated. They specifically bound to EGFR, not to the seven unrelated proteins as negative controls. They also bound to the three different human cancer cell lines, but not to the two cell lines as negative controls. They inhibited cell proliferation, migration and invasion and increased apoptosis of these three cancer cell lines. Two of them were tested for their anti-tumor effect in vivo and showed the anti-tumor activity in a mouse xenograft model for human lung cancer. Immunohistochemical staining of xenograft tumors also showed that their anti-tumor effects were associated with the inhibition of cancer cell proliferation and the promotion of cancer cell apoptosis. CONCLUSIONS: This study clearly demonstrated that the anti-EGFR sdAbs could inhibit cancer cell growth in vitro and tumor growth in vivo. They could be potential therapeutics for the treatment of different human cancers.

2.
Ultrasound Med Biol ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33039172

RESUMO

Children younger than 18 mo with developmental dysplasia of the hip (DDH) were treated with reduction and spica cast. X-Ray, computed tomography or magnetic resonance imaging (MRI) was used to evaluate reduction effectiveness. This study explored the hip medial ultrasonography method and anatomic structure sonograms. Twenty-eight children with DDH were enrolled. A total of 51 hips (24 left hips /27 right hips) were measured, including 30 affected hips and 21 normal hips. Various indices, including femoral head diameter (DIA), triradiate cartilage-femoral distance (TFD), acetabular-femoral distance (AFD) and ilium-femoral distance (IFD), were measured in the acetabular median coronal plane of ultrasound and the median coronal plane of MRI. The intra-group correlation coefficients for DIA, TFD, AFD and IFD were 0.968 (95% confidence interval: 0.917-0.985), 0.959 (0.929-0 976), 0.923 (0.869-0.955) and 0.950 (0914-0.971), respectively. Hip medial ultrasound and MRI exhibited good consistency. It is feasible to use hip medial ultrasound to evaluate the reduction of DDH in infants and children after spica cast.

3.
Orthop Surg ; 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33043614

RESUMO

PURPOSE: To evaluate the effect of anesthetic management on scoliosis surgery and review the incidence rate of perioperative adverse events. METHODS: This was a retrospective study and approved by the ethics committee. Patients who underwent scoliosis surgery from April 2011 to March 2018 in the Third Hospital of ChengDu were enrolled in this study. Characteristics of patients were obtained from the hospital's electronic records. The following information on patients was collected: preoperative assessment details, premedication, type of anesthesia and operation, the main postoperative outcome, and complications. Data were presented as the mean ± standard deviations (SD) for normally distributed continuous variables and numbers for categorical variables. Statistical analyses were performed using SPSS version 22.0. RESULTS: In total, 513 patients were enrolled in the present study. The main preoperative complication was cardiopulmonary dysfunction (386 cases, 75.24%). Anesthesia induction was performed with conscious tracheal intubation after oral surface anesthesia. In total, the common postoperative complications involved anesthesia (24 cases, 4.68%), surgery (23 cases, 4.48%), the respiratory system (138 cases, 26.90%), and the gastrointestinal tract (nine cases, 1.75%). The majority of postoperative complications were postoperative hypoxemia and hypercapnia, caused by poor cardiopulmonary function. Rare and serious complications still occurred. Three patients died in hospital. CONCLUSION: Our study demonstrated a high incidence of complications in scoliosis surgery, especially postoperative complications. Extreme postoperative vigilance is required and high-level monitoring of conditions is highly recommended.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33001018

RESUMO

BACKGROUND: Perampanel is a highly selective and non-competitive α-amino-3-hydroxy-5 -methyl-4-isoxazole propionate (AMPA) receptor (AMPAR) antagonist, which has been licensed as an orally administered antiepileptic drug in more than 55 countries. Recently, perampanel was found to exert neuroprotective effects in hemorrhagic and ischemic stroke models. OBJECTIVE: In this study, the protective effect of perampanel was investigated. METHOD: The protective effect of perampanel was investigated in an in vitro traumatic neuronal injury (TNI) model in primary cultured cortical neurons. RESULTS: We found that perampanel significantly preserved morphological changes, attenuated lactate dehydrogenase (LDH) release and inhibited caspase-3 activation after TNI. The TNI-induced necroptosis, as evidenced by flow cytometry, was markedly reduced by perampanel treatment. The results of western blot showed that perampanel decreased the expression and phosphorylation of the necroptotic factors, receptor protein interacting kinase 1 (RIPK1) and RIPK3. In addition, treatment with perampanel increased the phosphorylation of Akt and GSK3ß in a time-dependent manner up to 24 h after TNI. Treatment with the Akt inhibitor LY294002 partially reversed the protective effects of perampanel. CONCLUSION: Our present data suggest that necroptosis plays a key role in the pathogenesis of neuronal death after TNI, and that perampanel might have therapeutic potential for patients with traumatic brain injury (TBI).

5.
World J Surg Oncol ; 18(1): 258, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32998771

RESUMO

BACKGROUND: The examination of lymph nodes (LNs) plays an important role in the nodal staging of non-small cell lung cancer (NSCLC). For patients without LN metastasis, the main role of thorough LN examination is accurate staging, which weakens the effect of staging migration. To date, the role of hilar and intrapulmonary (N1) station LNs has not been fully appreciated. In this study, we aimed to confirm the significance of N1 LNs in long-term survival for stage IA-IIA NSCLC patients and to find the minimum number of LN to examine. METHODS: The data of patients who underwent radical lobectomy and were confirmed as having non-metastatic LNs from January 2008 to March 2018 were retrospectively screened. Pathology records were reviewed for the number of LNs examined. The Kaplan-Meier method and Cox regression model were used to identify survival and prognostic factors. RESULTS: The median number of resected N1 LNs was 8. The number of patients with 0-2 N1 LNs, 3-5 N1 LNs, 6-8 N1 LNs, 9-11 N1 LNs, and more than 11 N1 LNs examined was 181, 425, 477, 414, and 531, respectively. Sex (P = 0.004), age (P < 0.001), tumor size (P = 0.004), differentiation degree (P = 0.001), and number of N1 LNs examined (P = 0.008) were independent prognostic factors of overall survival. Gender (P = 0.006), age (P = 0.031), tumor size (P = 0.001), differentiation degree (P = 0.001), vascular invasion (P = 0.034), and number of N1 LNs examined (P = 0.007) were independent prognostic factors of disease-free survival. Compared with patients with 0-5 N1 LNs examined, patients with more than 5 N1 LNs examined had better OS (P = 0.015) and had better DFS (P = 0.015) if only a landmark 5-year follow-up was performed. CONCLUSION: Increasing the number of N1 LN examination might improve the long-term survival of T1-2N0 NSCLC patients. These data indicate that at least 6 N1 nodes examined is an essential part in surgical and pathological management but cannot prove this. This finding should be confirmed in a large, prospective randomized clinical study.

6.
Ecotoxicol Environ Saf ; 206: 111409, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33011510

RESUMO

To improve the effect of coal fly ash on the remediation of heavy metal polluted soils, the active silicate material (ASM) was prepared by coal fly ash and the remediation of lead polluted soils by ASM was investigated in this study. To study the reaction mechanism between ASM and Pb(II) in soil, the Pb(II) adsorption by ASM was investigated by a series of batch experiments. The result shows that the maximum adsorption capacity of ASM was 300.62 mg g-1 according to the Langmuir isotherm model. The average adsorption energy obtained from the D-K model revealed that the adsorption process of ASM is the ion-exchange process. To apply the ASM to the remediation of lead polluted soils, the soil stabilization experiment and pot experiment were carried out. The results reveal that ASM can reduce the mobility and bioavailability of lead in the soils by transforming the lead from exchangeable fraction, carbonate fraction and reducible fraction to oxidizable fraction and residual fraction. Moreover, ASM can improve the growth of pakchoi by promoting the production of chlorophyll. Furthermore, ASM can reduce the Pb accumulation of pakchoi by inhibiting the absorption of lead in the roots. It is anticipated that this study can provide a novel active silicate material for the application of coal fly ash in heavy metal pollution treatment.

7.
Hepatol Int ; 14(5): 723-732, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33026573

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) has rapidly become a major international public health concern. This study was designed to evaluate the clinical characteristics and risk factors of COVID-19-associated liver injury. METHODS: A fraction of 657 COVID-19 patients were retrospectively analyzed. Clinical and laboratory data were derived from electronic medical records and compared between patients with or without liver injury. Multivariate logistic regression method was used to analyze the risk factors for liver injury. RESULTS: Among 657 patients, 303 (46.1%) patients had liver injury with higher rate in severe/critically ill patients [148/257 (57.6%)] than those in moderate cases [155/400 (38.8%)]. The incidence of liver injury was much higher in male [192/303 (63.4%)] than female [111/303 (36.6%)], and in severe/critical patients [148/303 (48.8%)] with percutaneous oxygen saturation ≤ 93% [89/279 (31.9%)] or peak body temperature ≥ 38.5 °C [185/301 (61.5%)] on admission. Liver injury-related inflammations included increased white blood cells, neutrophils and decreased lymphocytes. More patients with liver injury than without had increased serum IL-2R, TNFα, ferritin, hsCRP, PCT, ESR, γ-GT, and LDH. Multivariate regression analysis revealed that increasing odds of liver injury were related to male, higher serum hsCRP (≥ 10 mg/L), and neutrophil-to-lymphocyte ratio (NLR) (≥ 5). Moreover, more deceased patients (14/82 (17%)) had significantly elevated serum TBIL than discharged patients [25/532 (4.7%)]. CONCLUSION: Liver injury is a common complication in COVID-19 patients. The potential risk factors of liver injury include male, hsCRP and NLR score. A close monitor of liver function should be warned in COVID-19 patients, especially in severe/critical individuals.

8.
BMC Genet ; 21(1): 119, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054745

RESUMO

BACKGROUND: Eating and cooking qualities (ECQs) of rice (Oryza sativa L.) determine consumer acceptance and the economic value of rice varieties. The starch physicochemical properties, i.e. amylose content, gel consistency, gelatinization temperature and pasting viscosity are important indices for evaluating rice ECQs. Genetic factors are required for development of rice varieties with excellent ECQs and association mapping is one of the promising approaches for discovering such associated genetic factors. RESULTS: A genome-wide association mapping was performed on a set of 253 non-glutinous rice accessions consisting of 83 indica and 170 japonica cultivated rice varieties through phenotyping for 11 ECQ traits in two consecutive years and genotyping with 210 polymorphic SSR and candidate-gene markers. These markers amplified 747 alleles with an average of 3.57 alleles per locus. The structure, phylogenetic relationship, and principal component analysis indicated a strong population differentiation between indica and japonica accessions and association mapping was thus undertaken within indica and japonica subpopulations. All traits showed a large phenotypic variation and highly significant phenotypic correlations were present between most of traits. A total of 33 and 30 loci were located for 11 ECQs in indica and japonica subpopulations respectively. Most of associated loci were overlapped with starch synthesis-related genes (SSRGs), and the Wx locus gathered 14 associated loci with the largest effects on amylose content, gel consistency and pasting viscosities. Eight subpopulation specific markers, RM588, Wx-(CT)n, SSI and SBE1 for indica subpopulation and RM550, Wxmp, SSIIa and SBE4 for japonica subpopulation, were identified, suggesting alleles of SSRGs showed the subspecific tendency. Nevertheless, allelic variation in SSIIa showed no tendency towards subspecies. One associated maker RM550 detected in japonica subpopulation for amylose content and pasting viscosity was verified a potential novel and stably expressed locus and could be selected for further fine mapping. CONCLUSION: This study illustrated the potential for dissecting genetic factors of complex traits in domesticated rice subspecies and provided highly associated markers to facilitate marker-assisted selection for breeding high-quality indica or japonica rice varieties.

9.
J Cardiothorac Surg ; 15(1): 315, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33059693

RESUMO

OBJECTIVE: To identify risk factors and long-term outcomes of acute kidney injury (AKI) in young patients who underwent type A acute aortic dissection (TA-AAD) emergency surgeries. METHODS: This retrospective study enrolled 121 consecutive patients less than 40 years old who received TA-AAD emergency surgeries between January 2014 to December 2018 in Nanjing Drum Tower hospital. The diagnosis of AKI was made based on the KDIGO criteria. Multivariable regression analysis was performed to identify risk factors for postoperative AKI. Kaplan-Meier curves were generated to compare long-term outcomes between patients with and without AKI complication after TA-AAD surgeries. RESULTS: Among all enrolled patients, AKI occurred in 51 patients (42.1%) and renal replacement therapy (RRT) was required in 15 patients (12.4%). The development of postoperative AKI was associated with increased 30-day mortality (P = 0.041), longer ICU stay time (P < 0.001) and hospital stay time (P = 0.006). Multivariable analysis indicated that elevated preoperative serum cystatin C (sCyC) (OR = 6.506, 95% CI: 1.852-22.855, P = 0.003) was the only independent risk factor for developing AKI. The areas under the receiver-operating characteristic curve (AUC) of preoperative sCyC was 0.800 (95% CI: 0.719, 0.882). Preoperative sCyC had a sensitivity of 64.7% and a specificity of 83.8% in diagnosing postoperative AKI with a cut-off value of 0.895 mg/L. In addition, our data suggested there was no difference discovered regarding long-term cumulative survival rate between patients with and without AKI during a median 29 months follow-up period. CONCLUSIONS: Postoperative AKI after TA-AAD surgeries was relatively common in young patients and associated with increased short-term mortality. Elevated preoperative sCyC was identified as an independent risk factor for AKI with potential diagnostic merit.

10.
Nanoscale ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33063798

RESUMO

With the booming development of flexible pressure sensors, the need for multifunctional and high-performance pressure sensor has become increasingly important. Although great progress has been made in the novel structure and sensing mechanism of the pressure sensor, the trade-off between the sensitivity and the wide-detection range has prevented its development, further restricting its application in wearable human-machine interfaces (WHMIs). Herein, a novel pressure sensor based on the hierarchical conductive fabric was fabricated and purposed as a WHMI. Poly(3,4-ethylenedioxythiophene) nanowires (PEDOT NWs) and cellulose nanofibers (CNF) were stacked on a conductive poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) fabric to form a special spatial multi-level hierarchical structure inside the fabric, which is a breakthrough for the improvement of the sensor's performance and makes the fabrication process of in situ polymerization suitable for large-scale production. The multi-level hierarchical structures endowed the pressure sensor with characteristics of high sensitivity (15.78 kPa-1), a wide-detection range from 30 Pa to 700 kPa, and outstanding stability toward compression and bending deformation. Benefiting from its excellent performance, a human-machine interface based on arrayed pressure sensors and signal processing system can control the illumination of the LED array and effectively capture finger motion to control the eight-direction movement of an unmanned aerial vehicle (UAV). This improved performance of the pressure sensor based on the hierarchical conductive fabric made it a widespread application in intelligent fabric, electronic skin, human-machine interfaces, and robotics.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33048773

RESUMO

To counter the outbreak of COVID-19, the accurate diagnosis of suspected cases plays a crucial role in timely quarantine, medical treatment, and preventing the spread of the pandemic. Considering the limited training cases and resources (e.g, time and budget), we propose a Multi-task Multi-slice Deep Learning System ( M3Lung-Sys) for multi-class lung pneumonia screening from CT imaging, which only consists of two 2D CNN networks, i.e., slice- and patient-level classification networks. The former aims to seek the feature representations from abundant CT slices instead of limited CT volumes, and for the overall pneumonia screening, the latter one could recover the temporal information by feature refinement and aggregation between different slices. In addition to distinguish COVID-19 from Healthy, H1N1, and CAP cases, our M3Lung-Sys also be able to locate the areas of relevant lesions, without any pixel-level annotation. To further demonstrate the effectiveness of our model, we conduct extensive experiments on a chest CT imaging dataset with a total of 734 patients (251 healthy people, 245 COVID-19 patients, 105 H1N1 patients, and 133 CAP patients). The quantitative results with plenty of metrics indicate the superiority of our proposed model on both slice- and patient-level classification tasks. More importantly, the generated lesion location maps make our system interpretable and more valuable to clinicians.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33071959

RESUMO

Background and Objective: Primary adrenal lymphoma is a rare, progressive, easily misdiagnosed adrenal tumor with a poor prognosis. There are limited data on its clinical characteristics, and these have been derived from small sample studies. This study aimed to identify the clinical characteristics and prognosis of primary adrenal lymphoma. Methods: This single-center study retrospectively analyzed data of 50 primary adrenal lymphoma patients treated between January 2008 and January 2018. Demographic information, biochemical indexes, computed tomography images, pathological findings, treatment regimens, and prognostic factors were analyzed. Results: The median age of onset was 60.3 years, and 30 (60.0%) of 50 patients were male. Abdominal pain was the most common symptom, followed by incidentaloma and B symptoms. On average, patients presented with elevated lactate dehydrogenase (348 IU/L, normal range 110-220 IU/L) and hydroxybutyrate dehydrogenase levels (287 IU/L, normal range 72-182 IU/L) and decreased high-density lipoprotein cholesterol levels (0.88 mmol/L, normal range > 0.9 mmol/L). Bilateral lesions in the adrenal glands were observed in 30 (60.0%) patients. Computed tomography showed that 42 (84%) patients had signs of infiltration. Diffuse large B-cell lymphoma was present in 44 (88%) patients. Immunohistochemistry revealed that 70.6% (12/17), 89.5% (17/19), 92.0% (23/25), and 68.8% (11/16) of patients were positive for MYC, p53, BCL2, and both MYC and BCL2, respectively. Combined chemotherapy was associated with a good prognosis. Conclusions: Early diagnosis of primary adrenal lymphoma depends on a combination of biochemical examination, imaging studies, and pathological biopsy, and combined chemotherapy may lead to a better prognosis.

13.
Nat Med ; 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32868878

RESUMO

An effective strategy to cure HIV will likely require a potent and sustained antiviral T cell response. Here we explored the utility of chimeric antigen receptor (CAR) T cells, expressing the CD4 ectodomain to confer specificity for the HIV envelope, to mitigate HIV-induced pathogenesis in bone marrow, liver, thymus (BLT) humanized mice. CAR T cells expressing the 4-1BB/CD3-ζ endodomain were insufficient to prevent viral rebound and CD4+ T cell loss after the discontinuation of antiretroviral therapy. Through iterative improvements to the CAR T cell product, we developed Dual-CAR T cells that simultaneously expressed both 4-1BB/CD3-ζ and CD28/CD3-ζ endodomains. Dual-CAR T cells exhibited expansion kinetics that exceeded 4-1BB-, CD28- and third-generation costimulated CAR T cells, elicited effector functions equivalent to CD28-costimulated CAR T cells and prevented HIV-induced CD4+ T cell loss despite persistent viremia. Moreover, when Dual-CAR T cells were protected from HIV infection through expression of the C34-CXCR4 fusion inhibitor, these cells significantly reduced acute-phase viremia, as well as accelerated HIV suppression in the presence of antiretroviral therapy and reduced tissue viral burden. Collectively, these studies demonstrate the enhanced therapeutic potency of a novel Dual-CAR T cell product with the potential to effectively treat HIV infection.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32864843

RESUMO

Multicolor fluorescent polymeric hydrogels (MFPHs) are three-dimensionally cross-linked hydrophilic polymer networks with tunable emission color. Different from the classic fluorescent materials used primarily in dry solid states or solutions, MFPHs exist as highly water-swollen quasi-solid state and thus present many promising properties of both solid and solution, including tissue-like mechanical properties, intrinsic soft and wet nature, fabulous biocompatibility, along with responsive volume, shape and fluorescence color change. These advantageous properties hold great potential in many frontier applications like sensing, bioimaging, information encoding, encryption, biomimetic actuators, and soft robotics. This review is intended to give an in-depth overview of the recent progress in the field of MFPHs with particular focus on the diverse construction methods and important demonstrated applications. Current challenges and future perspectives on MFPHs are also discussed to attract more research interest and promote the future design of MFPHs with fascinating functions and applications.

15.
Medicine (Baltimore) ; 99(33): e21498, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32871996

RESUMO

Adjuvant chemotherapy may cause alterations in serum lipids in postoperative breast cancer (BC) patients, but the specific alterations caused by different chemotherapy regimens remain unclear. The aim of this study was to investigate the status of serum lipids pre- and post-chemotherapy and to compare the side effects of different chemotherapy regimens on serum lipid.We retrospectively analysed the lipid profiles of 1934 consecutive postoperative BC patients who received one of the following chemotherapy regimens:The levels of triglycerides (TG), total cholesterols (TC), and low-density lipoprotein (LDL-C) were significantly elevated in patients who received chemotherapy regimens above (P < .001). With respect to different chemotherapy regimens, FEC had less side effects on lipid profiles (TG (P = .006), high-density lipoprotein (HDL-C) (P < .001), and LDL-C (P < .001)) than TC regimen and AC-T and EC-T regimen. Also, the incidence of newly diagnosed dyslipidemia after chemotherapy was lower in FEC group than TC group and AC-T and EC-T group (P < .001). Additionally, the magnitude of the alterations in lipid profiles (TG, TC, HDL-C, and LDL-C) was greater in premenopausal patients than that of the postmenopausal patients (P = .004; P < .001; P = .002; P = .003, respectively). Moreover, after adjusting for multiple baseline covariates, anthracycline-plus-taxane-based regimens (AC-T and EC-T) were still statistically associated with a high level of TG (P = .004) and a low level of HDL-C (P = .033) after chemotherapy compared with FEC regimen. Also, body mass index (BMI) > 24 was associated with abnormal lipid profiles (TG, TC, HDL-C, LDL-C) post-chemotherapy compared with BMI ≤ 24 (P < .001; P = .036; P = .012; P = .048, respectively).BC patients receiving chemotherapy may have elevated lipid profiles, and anthracycline-based regimen had less side effects on lipid profiles compared with regimens containing taxane. Therefore, it is necessary to take lipid metabolism into consideration when making chemotherapy decisions and dyslipidemia prevention and corresponding interventions are indispensable during the whole chemotherapy period.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Lipídeos/sangue , Adulto , Idoso , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
16.
Mutat Res ; 856-857: 503232, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32928372

RESUMO

miR-34a has been identified as a tumor suppressor microRNA (miRNA) involved in the P53 network. Its expression levels correlate to carcinogenesis, which are generally lower in tumor tissue and higher in response to DNA damage. In this study, the response of miR-34a from exposure to genotoxic agents in human lymphoblastoid TK6 cells was evaluated to assess whether the expression of this miRNA could be used as an early indicator for genotoxic damage in mammalian cells. TK6 cells were treated with seven genotoxic agents with different mode-of-actions (cisplatin, N-ethyl-N-nitrosourea, etoposide, mitomycin C, methyl methanesulphonate, taxol, and X-ray radiation) and a non-genetic toxin (usnic acid) at different concentrations for four hours (except for X-rays) and the expression levels of miR-34a were measured 24 h after the beginning of the treatments. The expression levels of miR-34a were significantly increased by these genetic toxins in a dose-dependent manner, while no significant change in miRNA expression was found in the usnic acid-treated cells. These results suggest that miR-34a can respond to genotoxic insults sensitively; thus, miR-34a expression has the potential to be used to evaluate genotoxicity of agents.

17.
FASEB J ; 2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-32918771

RESUMO

Subarachnoid hemorrhage (SAH), mostly caused by aneurysm rupture, is a pathological condition associated with oxidative stress and neuroinflammation. Toll-like receptors (TLRs) are a family of key regulators of neuroinflammation, and RNF216 is an E3 ubiquitin-protein ligase that regulates TLRs via ubiquitination and proteolytic degradation. However, the role of RNF216 in SAH has not been determined. In this study, we investigated the biological function of RNF216 in experimental SAH models both in vitro and in vivo. The expression of RNF216 was found to be upregulated in cortical neurons after oxyhemoglobin (OxyHb) treatment, and increased RNF216 expression was also observed in brain tissues in the single-hemorrhage model of SAH. Downregulation of RNF216 expression by short interfering RNA (siRNA) transfection significantly reduced cytotoxicity and apoptosis after OxyHb exposure. The results of western blot showed that the RNF216-mediated neuronal injury in vitro was associated with the regulation of the Arc-AMPAR pathway, which was related to intracellular Ca2+ dysfunction, as evidenced by Ca2+ imaging. In addition, knockdown of RNF216 in vivo using intraventricular injection of siRNA was found to attenuate brain injury and neuroinflammation via the Arc-AMPAR pathway after SAH in the animal model. In summary, we demonstrated that silence of RNF216 expression protects against neuronal injury and neurological dysfunction in experimental SAH models. These data support for the first time that RNF216 may represent a novel candidate for therapies against SAH.

18.
Gen Physiol Biophys ; 39(4): 363-371, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32902405

RESUMO

The E3 ligase RING finger and WD repeat domain 3 (RFWD3) can stabilize p53 in response to DNA damage, participate in replication checkpoint, and have an important role in multiple myeloma, testicular germ cell tumor and lung carcinogenesis. Its expression and molecular mechanisms have never been explored in gastric cancer. In present study, the RFWD3 was over-expressed in both AGS and HGC-27 gastric cancer cells are found. Knockdown of RFWD3 suppressed cells proliferation activity of gastric cancer cells. And further study showed down-regulation of RFWD3 promotes cell apoptosis, suppresses cell migration and invasion and blocks G2/M cell cycle progression, which may be related with AKT, ERK/P38 and Slug pathways. Collectively, the results of the present study showed that RFWD3 might be a candidate oncogene for gastric cell proliferation and may have an important role in gastric carcinogenesis.

19.
J Hand Surg Eur Vol ; : 1753193420951341, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32903127

RESUMO

We report the clinical findings of congenital peripheral nerve hypoplasia in seven patients. All seven children presented with unilateral ulnar or median nerve palsy or both. They were assessed clinically, and nerve diameters were assessed with ultrasonography and compared with the contralateral limb. Nerve conduction studies were performed in five children, and the nerves were explored in the four children who presented with accompanying constriction bands. By ultrasonography, the mean diameter of the ulnar nerve was 63% and 29% when compared with the normal arm and forearm, respectively, and the mean diameter of the median nerve was 63% and 46%. Hypoplasia in the nerve was not confined to constriction points but occurred in the entire upper limb in all seven cases. These patients were followed for an average of 12 months (range 6 to 30). Despite neurolysis and surgical decompression in four patients, none of the nerve palsies had recovered. The clinical findings suggest that this condition cannot be explained by simple mechanical compression, and more extensive pathological changes in the involved upper limb are evident in this rare disease.Level of evidence: IV.

20.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(10): 1162-1166, 2020 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-32924126

RESUMO

OBJECTIVE: To explore the genetic etiology of a patient with glycogen accumulation type Ⅰa with gout as the main clinical feature. METHODS: Clinical data of the patient was collected. The patient and her parents were subjected to next generation sequencing (NGS). Suspected pathogenic variation was verified by Sanger sequencing. RESULTS: The patient, a 30-year-old women, mainly manifested hyperuricemia, chronic gouty arthritis, fasting hypoglycemia, hypertriglyceridemia, hyperlactatemia, hepatomegaly, urolithiasis, and gradually developed liver nodules and renal dysfunction. NGS revealed that she has carried c.648G>T (exon 5) and c.260delG (exon 2) compound heterozygous variants of the G6PC gene, which were respectively inherited from her father (phenotypically normal) and mother (with hyperuricemia). The c.260delG variant was unreported previously. Bioinformatic analysis indicated that both variants are pathogenic. CONCLUSION: The compound heterozygous variants of the G6PC gene probably underlay the glycogen storage disease Ⅰa in this patient. G6PC gene mutations should be excluded in young women with hyperuricemia and /or gout.

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