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1.
Clin Rheumatol ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31950440

RESUMO

The first name of the co-author of the above article was presented incorrect in the published version. The author name "Miangliang Qiu" should read "Mingliang Qiu" as mentioned above.

2.
Arch Pharm (Weinheim) ; : e1900294, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31894862

RESUMO

A series of (3-benzyl-5-hydroxyphenyl)carbamates were evaluated as new antibacterial agents. Several compounds showed potent inhibitory activity against sensitive and drug-resistant Gram-positive bacteria. The compounds are ineffective against all tested Gram-negative bacteria. The structure of the ester group exerted a profound effect on antibacterial activity. 4,4-Dimethylcyclohexanyl carbamate 6h exhibited the most potent inhibitory activity against the standard and clinically isolated Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecalis (minimum inhibitory concentration = 4-8 µg/ml) strains. The preliminary experimental evidence indicated that these carbamates target the bacterial cell wall and share a similar mechanism of action with vancomycin.

3.
Cancer Lett ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31904481

RESUMO

Long noncoding RNAs play significant roles in diverse cancers. In this study, we found that LINC00240 expression was markedly increased in cervical cancer. Functional in vitro assays in cervical cancer cells showed that LINC00240 enhanced the growth, migration, and invasion of cervical cancer cells. The target of LINC00240 was confirmed as microRNA(miR)-124-3p. Inhibition of miR-124-3p significantly enhanced cervical cancer progression via targeting of STAT3, which is greatly activated in tumor-infiltrating immune cells. LINC00240 expression was able to induce STAT3 expression via sponging of miR-124-3p, and showed a positive association with STAT3 expression in cervical cancer tissues. MHC class I-related chain (MIC)-A plays a key role in activating natural killer T (NKT) cells and serves as a downstream target of STAT3. Here, MICA was inhibited by up-regulation of LINC00240, and could be rescued by STAT3 knockdown. In addition, LINC00240 overexpression suppressed the cytotoxic activity of NKT cells by affecting the STAT3/MICA axis. Subsequently, we found that LINC00240 expression promoted cervical cancer progression via induction of miR-124-3p/STAT3/MICA-mediated NKT cell tolerance. Considering these findings, we conclude that LINC00240 might be a novel target for cervical cancer.

4.
J Cell Mol Med ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31793207

RESUMO

Both PNPLA3 I148M and hepatic inflammation are associated with nonalcoholic fatty liver disease (NAFLD) progression. This study aimed to elucidate whether PNPLA3 I148M is involved in NF-kB-related inflammation regulation in NAFLD. HepG2 cells homozygous for the PNPLA3 I148M mutation were used. The human PNPLA3 promoter sequence was screened for NF-kB binding sites using the MATCH and PATCH tools. NF-kB-mediated transcriptional regulation of the PNPLA3 gene was assessed by luciferase reporter assay, EMSA and ChIP-qPCR. Wild-type (I148I) and mutant (M148M) PNPLA3 were overexpressed using stable lentivirus-mediated transfection. The pCMV vector and siRNA were transiently transfected into cells to direct NF-kB overexpression and PNPLA3 silencing, respectively. A putative NF-kB binding site in the human PNPLA3 promoter was shown to be necessary for basal and NF-kB-driven transcriptional activation of PNPLA3 and protein/DNA complex formation. Supershift analysis demonstrated a protein/DNA complex specifically containing the NF-kB p65 and p50 subunits. ChIP-qPCR confirmed the endogenous binding of NF-kB to the human PNPLA3 promoter in response to NF-kB overexpression and palmitic acid (PA) challenge. The silencing of PNPLA3 blocked the overexpression of NF-kB or PA-induced TNF-α up-regulation. Moreover, mutant PNPLA3 overexpression prevented NF-kB inhibitor-induced down-regulation of TNF-α expression in PA-treated HepG2 cells. Finally, the overexpression of mutant but not wild-type PNPLA3 increased TNF-α expression and activated the ER stress-mediated and NF-kB-independent inflammatory IRE-1α/JNK/c-Jun pathway. Human PNPLA3 was shown to be a target of NF-kB, and PNPLA3 I148M mediated the regulatory effect of NF-kB on inflammation in PA-treated HepG2 cells, most likely via the IRE-1α/JNK/c-Jun ER stress pathway.

5.
Inflammation ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31802382

RESUMO

Ellipticine, a natural product from Ochrosia elliptica, has been broadly investigated for its anticancer effects. Although inflammation has been clearly identified as a key factor in the onset and progression of cancer, the relationship between ellipticine and inflammation remains unknown. Hence, the aims of the present study were to assess the effects of ellipticine on the inflammatory responses to lipopolysaccharide (LPS)-induced macrophages and to potentially identify the underlying mechanisms involved. Viability testing showed that ellipticine was not significantly toxic to Raw264.7 cells and actually conveyed protective effects to LPS-stimulated Raw264.7 cells and human peripheral blood monocytes by decreasing the secretion of inflammatory factors (TNF-α and IL-6). The results of western blot analysis and electrophoretic mobility shift assays showed that ellipticine markedly suppressed LPS-induced activation of the JNK/AP-1 (c-Fos and c-Jun) signaling pathway, but not ERK/p38/NF-κB pathway (p65 and p50) activation. Furthermore, ellipticine reduced the inflammatory response and mortality in a mouse model of LPS-induced endotoxic shock. Collectively, these data indicate that ellipticine may be a potential therapeutic agent for the treatment of inflammation-associated diseases.

6.
Clin Rheumatol ; 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31879859

RESUMO

OBJECTIVE: miR-150-5p has been implicated in the regulation and onset of immune diseases. We investigated the effects of miR-150-5p on the functions of RA synovial fibroblasts (RASFs). METHOD: The binding site between suppressor of cytokine signaling 1 (SOCS1) and miR-150-5p was analyzed using European Bioinformatics Institute database, and the 3' UTR of SOCS1 mRNA, including the binding site, was amplified and ligated to the 3'-end of LUC2 gene in the pmirGL0 dual-luciferase vector. The pmirGL0 vector and corresponding mimics were subsequently co-transfected into 293T cells to compare the relative fluorescence intensity of LUC2 between the miR-150-5p mimics and the negative control (NC) mimics groups. Further, the RASF cell line MH7A was transfected with miR-150-5p or NC mimics and subjected to flow cytometric analysis, cell counting kit-8 assay, western blot analysis, qPCR, and enzyme-linked immunosorbent (ELISA) assay 48 h after transfection. RESULTS: miR-150-5p mimics resulted in a lower cell apoptotic rate and proportion of cells in the S phase. Using a dual-luciferase reporter gene assay, we then found that SOCS1 is a potential target of miR-150-5p. Compared with NC mimics, miR-150-5p mimics significantly decreased the protein and mRNA expression levels of SOCS1. ELISA assay showed that miR-150-5p mimics increased interleukin-6 level in the cell culture medium but did not influence tumor necrosis factor-alpha levels. CONCLUSIONS: Overall, the growth-promoting effect of miR-150-5p on MH7A cells may be attributed to the miR-150-5p-induced degradation of SOCS1 mRNA, suggesting a potential therapeutic target for RA.Key Points• SOCS1 is a potential target of miR-150-5p.• miR-150-5p promoted the growth of RASF cell line MH7A.• miR-150-5p increased the secretion of IL-6 but did not significantly affect TNF-α levels in MH7A cells.

7.
Exp Ther Med ; 18(6): 4820-4828, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31772647

RESUMO

Dexmedetomidine (DEX) is widely used in perioperative settings for analgesia and sedation; however, little is known about its effects on the hypoxia-induced progression of tumor cells. In the present study, the effects of DEX on hypoxia-induced growth and metastasis of lung cancer cells and colorectal cancer cells was examined. A549 cells and HCT116 cells were treated with normoxia, hypoxia, co-treatment of hypoxia and DEX, and atipamezole (an α2 adrenoceptor antagonist) for 4 h. The proliferation rate of cells was determined by MTT assays. Cell metastatic potential was evaluated by Transwell assays. Survivin and hypoxia inducible factor (HIF)-1α were detected by western blotting. Matrix metalloproteinase (MMP)-2 and MMP-9 were measured using reverse transcription-quantitative PCR. It was demonstrated that hypoxia treatment promoted the proliferation and may promote the metastasis of the two cancer cell lines. DEX substantially contributed to the survival and aggressiveness of the two cancer cell lines following hypoxia. Furthermore, DEX upregulated the expression of survivin, MMP-2, MMP-9 and HIF-1α in the two cancer cell lines in response to hypoxia. Finally, the effects of DEX on the hypoxia-induced growth and metastatic potential of cancer cells were reversed by atipamezole. Collectively, DEX enhances the hypoxia-induced progression of lung cancer cells and colorectal cancer cells by regulating HIF-1α signaling, which may be associated with the α2 adrenoceptor pathway.

8.
Medicine (Baltimore) ; 98(48): e18000, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770212

RESUMO

RATIONALE: Bladder cancer (BC) is commonly diagnosed in the urinary system and the most common subtype is transitional urothelial carcinoma (TCC). Even with the best treatment, tumor recurrence and metastases always occur. While clinicians commonly observe the metastases to pelvic lymph nodes, liver, lung, and bone, it may infrequently spread to some uncommon locations. PATIENT CONCERNS: The patient was a 67-year-old man with a diagnosis of high-grade TCC with squamous differentiation in the bladder and prostate. Subsequently, radical cystoprostatectomy, adjuvant radiotherapy, and chemotherapy were performed. However, he felt intermittent right scrotal pain about 1 year later. DIAGNOSIS: Ultrasound strongly suggested a testicular neoplasm of right testis, but the left was normal. INTERVENTIONS: The patient underwent a right radical orchiectomy and histopathology confirmed testicular metastatic neoplasm from bladder. Moreover, further examination with positron emission tomography revealed no visible distant spread of the urothelial carcinoma. OUTCOMES: No signs of tumor recurrence or distant metastasis were visible under follow-up 1 year after radical orchiectomy. LESSONS: Testicular mass may be metastatic tumor during follow-up for patients who were diagnosed as BC, especially for TCC with variant histology. The reason of this could be explained of residual micrometastases after surgery and need more examination to discover local micrometastases to apply more aggressive treatment.

9.
Br J Haematol ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674662

RESUMO

The relevance of donor-specific human leukocyte antigen (HLA) antibodies in HLA-mismatched haematopoietic cell transplant (HCT) is known, but the importance of HLA antibodies in HLA-matched HCT is unclear. We hypothesized that HLA antibodies detected before HCT would cause platelet transfusion refractoriness during HCT and investigated this in a multi-centre study. Pre-HCT samples from 45 paediatric patients with sickle cell disease (SCD) undergoing HLA-matched HCT were tested for HLA class I antibodies. The number of platelet transfusions received before day +45 was compared between those with and without antibodies. Thirteen of 45 (29%) patients had a positive HLA class I antibody screen, and these patients received significantly more platelet transfusions than patients without antibodies (median 19 vs. 7·5, P = 0·028). This platelet transfusion association remained significant when controlling for conditioning regimen. Among alloimmunized patients, there was no association between the panel-reactive antibody and the number of platelet transfusions. Patients with HLA class I antibodies also had a higher incidence of acute graft-versus-host disease (GVHD): 6/13 (46%) vs. 3/32 (9%), P = 0·011. Pre-HCT HLA class I alloimmunization is associated with increased platelet transfusion support and acute GVHD in paediatric HLA-matched HCT for SCD. Further studies are needed to investigate the pathobiology of this association.

10.
J Org Chem ; 84(19): 12301-12313, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31482711

RESUMO

A copper-catalyzed protocol for the construction of various 2-aryl(alkyl)-3-acylquinolines or 3-arylquinolines using readily available anthranils and 1,3-diketones or aldehydes as starting materials is reported herein. Dioxygen as the sole oxidant and hexafluoroisopropanol as the solvent play an important role in both procedures. This ring-opening/reconstruction strategy involving N-O bond cleavage and C-N/C-C bond formation features high yields and broad substrate scope.

11.
Stat Appl Genet Mol Biol ; 18(5)2019 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-31525158

RESUMO

We propose a new bi-level feature selection method for high dimensional accelerated failure time models by formulating the models to a single index model. The method yields sparse solutions at both the group and individual feature levels along with an expedient algorithm, which is computationally efficient and easily implemented. We analyze a genomic dataset for an illustration, and present a simulation study to show the finite sample performance of the proposed method.

12.
Front Immunol ; 10: 1647, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379845

RESUMO

Background: Antibody-dependent cellular cytotoxicity (ADCC), which mainly mediated by natural killer (NK) cells, may play a critical role in human immunodeficiency virus type-1 (HIV-1) disease progression. However, the potential mechanisms that affecting NK-mediated ADCC response are still not well-elucidated. Methods: Antigen-antibody complex model of Ab-opsonized P815 cells was adopted to induce a typical non-specific ADCC response. The capacities of HIV-1 specific NK-ADCC were measured by using the combination model of gp120 protein and plasma of HIV-1 elite controllers. The levels of plasma cytokine were measured by ELISA. Anti-IL-2 blocking antibody was used to analyze the impact of activated CD56+ T cells on NK-ADCC response. Results: IL-2, IL-15, IFN-α, and IFN-ß could effectively enhance the non-specific and HIV-1-specific NK-ADCC responses. Compared with healthy controls, HIV-1-infected patients showed decreased plasma IL-2 levels, while no differences of plasma IFN-α, IL-15, and IFN-ß were presented. IL-2 production was detected from CD56+ T cells activated through antibody-dependent manner. The capability of NK-ADCC could be weakened by blocking IL-2 secretion from activated CD56+ T cells. Although no difference of frequencies of CD56+ T cells was found between HIV-1-infected patients and healthy controls, deficient IL-2 secretion from activated CD56+ T were found in chronic HIV-1 infection. Conclusions: The impaired ability of activated CD56+ T cells to secreting IL-2 might contribute to the attenuated NK cell-mediated ADCC function in HIV-1 infection.

13.
Clin Nucl Med ; 44(8): 648-649, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31274612

RESUMO

Findings of Tc-DTPA renal scintigraphy of a retroperitoneal malignant peripheral nerve sheath tumor are reported here. The patient was a 48-year-old woman who presented discomfort and intermittent dull pain in the left upper quadrant of the abdomen for approximately 3 weeks.


Assuntos
Rim/diagnóstico por imagem , Neurofibrossarcoma/diagnóstico por imagem , Neurofibrossarcoma/patologia , Neoplasias Retroperitoneais/diagnóstico por imagem , Neoplasias Retroperitoneais/patologia , Pentetato de Tecnécio Tc 99m , Feminino , Humanos , Pessoa de Meia-Idade , Cintilografia
14.
Stat Med ; 38(23): 4574-4582, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31304613

RESUMO

Feature selection is an important initial step of exploratory analysis in biomedical studies. Its main objective is to eliminate the covariates that are uncorrelated with the outcome. For highly correlated covariates, traditional feature selection methods, such as the Lasso, tend to select one of them and eliminate the others, although some of the eliminated ones are still scientifically valuable. To alleviate this drawback, we propose a feature selection method based on covariate space decomposition, referred herein as the "Decomposition Feature Selection" (DFS), and show that this method can lead to scientifically meaningful results in studies with correlated high dimensional data. The DFS consists of two steps: (i) decomposing the covariate space into disjoint subsets such that each of the subsets contains only uncorrelated covariates and (ii) identifying significant predictors by traditional feature selection within each covariate subset. We demonstrate through simulation studies that the DFS has superior practical performance over the Lasso type methods when multiple highly correlated covariates need to be retained. Application of the DFS is demonstrated through a study of bipolar disorders with correlated biomarkers.

15.
IEEE Trans Image Process ; 28(12): 6091-6102, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31251187

RESUMO

Large-deformation image registration is important in theory and application in computer vision, but is a difficult task for non-rigid registration methods. In this paper, we propose a structural Tensor and Driving force-based Log-Demons algorithm for it, named TDLog-Demons for short. The structural tensor of an image is proposed to obtain a highly accurate deformation field. The driving force is proposed to solve the registration issue of large-deformation that often causes Log-Demons to trap into local minima. It is defined as a point correspondence obtained via multisupport-region-order-based gradient histogram descriptor matching on image's boundary points. It is integrated into an exponentially decreasing form with the velocity field of Log-Demons to move the points accurately and to speed up a registration process. Consequently, the driving force-based Log-Demons can well deal with large-deformation image registration. Extensive experiments demonstrate that the TDLog-Demons not only captures large deformations at a high accuracy but also yields a smooth deformation.

16.
Clin Exp Gastroenterol ; 12: 219-229, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190949

RESUMO

Purpose: The incidence of esophageal adenocarcinoma (EAC) has increased by 700% in Western countries over the last 30 years. Although clinical guidelines call for endoscopic surveillance for EAC among high-risk populations, fewer than 5% of new EAC patients are under surveillance at the time of diagnosis. We studied the accuracy of combined cytopathology and MUC2 immunohistochemistry (IHC) for screening of Intestinal Metaplasia (IM), dysplasia and EAC, using specimens collected from the EsophaCap swallowable encapsulated cytology sponge from Canada and United States. Patients and methods: By comparing the EsophaCap cytological diagnosis with concurrent endoscopic biopsies performed on the same patients in 28 cases, we first built up the cytology diagnostic categories and criteria. Based on these criteria, 136 cases were evaluated by both cytology and MUC2 IHC with blinded to patient biopsy diagnosis. Results: We first set up categories and criteria for cytological diagnosis of EscophaCap samples. Based on these, we divided our evaluated cytological samples into two groups: non-IM group and IM or dysplasia or adenocarcinoma group. Using the biopsy as our gold standard to screen IM, dysplasia and EAC by combined cytology and MUC2 IHC, the sensitivity and specificity were 68% and 91%, respectively, which is in the range of clinically useful cytological screening tests such as the cervical Pap smear. Conclusions: Combined EsophaCap cytology and MUC2 IHC could be a good screening test for IM and Beyond.

17.
Cancer Manag Res ; 11: 4327-4333, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190997

RESUMO

Purpose: To investigate the prevention effect of low-temperature atomization inhalation for radiation induced oral mucositis (OM) in patients with head and neck cancer (HNC) undergoing radiotherapy. Patients and methods: A total of 68 patients with HNC (including nasopharyngeal cancer) undergoing radiotherapy were divided into an intervention group (33 cases) and a control group (35 cases). During radiotherapy, the intervention group received low-temperature (between 4°C and 8°C) atomization inhalation; while the control group received normal temperature (between 18°C and 24°C) atomization inhalation. Atomization inhalation was performed twice a day, 20 minutes per time, using distilled water. The incidence and severity of OM was evaluated every week during radiotherapy. The comparation was made between the two groups. Results: The two groups were comparable among age, sex, Eastern Cooperative Oncology group (ECOG) score, body mass index (BMI) before radiotherapy, BMI loss during radiotherapy, original tumor site, pathological type, TNM stage, and mean oral cavity irradiated dose. There was a significant difference in the incidence of OM between the two groups (P<0.05). There were fewer patients with severe OM in the intervention group compared to the control group (P<0.05). The onset time of OM in the intervention group was delayed by about 4 days compared to that in the control group (P<0.05). Low-temperature atomization inhalation helped to avoid radiotherapy interruption in the intervention group. No patient in the intervention group suffered any adverse reaction for low-temperature atomization inhalation treatment. Conclusions: Low-temperature atomization inhalation can reduce the incidence and severity of OM, and slow down the progression process of it. It can be used as a new prevention method during radiotherapy, and should be promoted in clinical practice.

18.
Clin Nucl Med ; 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31162263

RESUMO

Findings of Tc-DTPA renal scintigraphy of a retroperitoneal malignant peripheral nerve sheath tumor are reported here. The patient was a 48-year-old woman who presented discomfort and intermittent dull pain in the left upper quadrant of the abdomen for approximately 3 weeks.

19.
Nat Commun ; 10(1): 2257, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31113957

RESUMO

A major barrier to human immunodeficiency virus (HIV) cure is the existence of viral reservoirs that lead to viral rebound following discontinuation of antiretroviral therapy (ART). We postulate that enhancing cytotoxic T lymphocytes (CTL) targeting conserved envelope (Env) regions can eliminate HIV infected cells in latency. Here, we evaluate the use of adoptively transferred HIV vaccine-induced subtype C Env-specific CTLs in a macaque subtype B simian-human immunodeficiency virus (SHIV) model to determine whether plasma viremia can be controlled after ART interruption. We demonstrate that adoptive cellular therapy (ACT) using autologous Env-specific T cells augmented by therapeutic vaccination can suppress ART-free viral rebound in the SHIV model. Furthermore, phenotypic and functional characterization of adoptively transferred cells in ACT-responsive and nonresponsive animals support a critical role for cross-reactive central memory T cells in viremia control. Our study offers an approach to potentiate immunological suppression of HIV in the absence of antiviral drugs.

20.
Ann Pharmacother ; 53(10): 1005-1019, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31129978

RESUMO

Background: Adverse drug outcomes in the elderly have led to the development of lists of potentially inappropriate medications (PIMs), such as the Beers criteria, and these PIMs have been studied widely; however, it is still unclear whether PIM use is predictive of adverse outcomes in older people. Objective: To qualitatively examine the associations between exposure to PIMs from the general Beers criteria and the Screening Tool of Older Persons' Prescriptions list and adverse outcomes, such as adverse drug reactions (ADRs)/adverse drug events (ADEs), hospitalization, and mortality. Methods: Specified databases were searched from inception to February 1, 2018. Two reviewers independently selected studies that met the inclusion criteria, assessed study quality, and extracted data. Data were pooled using Stata 12.0. The outcomes were ADRs/ADEs, hospitalization, and mortality. Results: A total of 33 studies met the inclusion criteria. The combined analysis revealed a statistically significant association between ADRs/hospitalizations and PIMs (odds ratio [OR] = 1.44, 95% CI = 1.33-1.56; OR = 1.27, 95% CI = 1.20-1.35), but no statistically significant association was found between mortality and PIMs (OR = 1.04; 95% CI = 0.75-1.45). It is interesting to note that the results changed when different continents/criteria were used for the analysis. Compared with the elderly individuals exposed to 1 PIM, the risk of adverse health outcomes was much higher for those who took ≥2 PIMs. Conclusion and Relevance: We recommend that clinicians avoid prescribing PIMs for older adults whenever feasible. In addition, the observed associations should be generalized to other countries with different PIM criteria with caution.

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