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1.
Medicine (Baltimore) ; 100(18): e25639, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950941

RESUMO

BACKGROUND: Salvianolate, a common drug for stabilizing heart disease and Angina Pectoris, is considered to be off-label for preventing venous thromboembolism (VTE) or anticoagulation at present. However, many clinical studies have showed that salvianolate can effectively inhibit the deep-vein thrombosis (DVT) incidence, and prevent VTE of perioperative patients in the real world in China. OBJECTIVE: This analysis aimed to evaluate the effectiveness and safety of salvianolate in preventing VTE in perioperative patients. METHODS: Databases of PubMed, Cochrane Library, Embase, CNKI, Wanfang and VIP were searched until July 2019. Literature retrieval, data extraction and quality assessment were independently completed by two researchers and checked with each other. Review Manager 5.2 software was applied for meta-analysis. RESULTS: A total of 429 studies were retrieved, including 11 randomized controlled trials (RCTs) with a total of 1149 subjects. Compared with low molecular weight heparin (LMWH) group alone, salvianolate combined LMWH group had lower DVT incidence in preventing perioperative thrombosis (2.75% and 14.23%, OR: 0.21, 95% CI:[0.08,0.53]; P = .0009). The incidence of adverse reactions of experimental group was similar to that of control group (1.79% and 2.31%, OR: 0.65, 95% CI:[0.18,2.35]. P = .51). Compared with the control group, D-dimer level (D-D), platelet count (PLT), fibrinogen (FIB), whole blood high shear viscosity (WBHSV), and whole blood low shear viscosity (WBLSV) were all significantly decreased (P < .01), and prothrombin time (PT) was significantly increased (P < .05). CONCLUSION: Salvianolate combined LMWH has better effectiveness and the same safety in preventing venous thromboembolism in perioperative patients. However, due to the small number of included literatures, large sample studies are still needed to further verify this conclusion.

2.
Environ Pollut ; 285: 117237, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33957515

RESUMO

Methane emitted by insects is considered to be an important source of atmospheric methane. Here we report the stimulation of methane emission in the cockroach Periplaneta americana and termite Coptotermes chaohuensis, insects with abundant methanogens, by neonicotinoids, insecticides widely used to control insect pests. Cycloxaprid (CYC) and imidacloprid (IMI) caused foregut expansion in P. americana, and increased the methane emission. Antibiotics mostly eliminated the effects. In P. americana guts, hydrogen levels increased and pH values decreased, which could be significantly explained by the gut bacterium community change. The proportion of several bacterium genera increased in guts following CYC treatment, and two genera from four could generate hydrogen. Hydrogen is a central intermediate in methanogenesis. All increased methanogens in both foregut and hindgut used hydrogen as electron donor to produce methane. Besides, the up-regulation of mcrA, encoding the enzyme for the final step of methanogenesis suggested the enhanced methane production ability in present methanogens. In the termite, hydrogen levels in gut and methane emission also significantly increased after neonicotinoid treatment, which was similar to the results in P. americana. In summary, neonicotinoids changed bacterium community in P. americana gut to generate more hydrogen, which then stimulated gut methanogens to produce and emit more methane. The finding raised a new concern over neonicotinoid applications, and might be a potential environmental risk associated with atmospheric methane.

3.
Viruses ; 13(3)2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33809549

RESUMO

During October 2020-January 2021, we isolated a total of 67 highly pathogenic avian influenza (HPAI) H5N8 viruses from wild birds and outbreaks in poultry in South Korea. We sequenced the isolates and performed phylogenetic analysis of complete genome sequences to determine the origin, evolution, and spread patterns of these viruses. Phylogenetic analysis of the hemagglutinin (HA) gene showed that all the isolates belong to H5 clade 2.3.4.4 subgroup B (2.3.4.4b) and form two distinct genetic clusters, G1 and G2. The cluster G1 was closely related to the 2.3.4.4b H5N8 HPAI viruses detected in Europe in early 2020, while the cluster G2 had a close genetic relationship with the 2.3.4.4b H5N8 viruses that circulated in Europe in late 2020. A total of seven distinct genotypes were identified, including five novel reassortants carrying internal genes of low pathogenic avian influenza viruses. Our Bayesian discrete trait phylodynamic analysis between host types suggests that the viruses initially disseminated from migratory waterfowl to domestic duck farms in South Korea. Subsequently, domestic duck farms most likely contributed to the transmission of HPAI viruses to chicken and minor poultry farms, highlighting the need for enhanced, high levels of biosecurity measures at domestic duck farms to effectively prevent the introduction and spread of HPAI.

4.
Epidemiol Health ; : e2021020, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33831295

RESUMO

Objectives: To estimate the prevalence of edentulism according to sociodemographic variables of Korean adults between 2007-2018 and to analyze the trends. Methods: This study analysis was completed using raw data from the Korea National Health and Nutrition Examination Survey (KNHANES) from 2007-2018. Edentulism was defined as the absence of upper and lower teeth or the retained root of the missing teeth. For the prevalence of edentulism, complex sample frequency analysis and regression analysis were performed according to the sociodemographic variables to represent national population. Korean population structure in 2005 was exploited as a standard population to calculate age-standardized edentulism. Results: The prevalence of edentulism in 2016~2018 was 9.72% in the Korean elderly and the change of age-standardized edentulism steadily declined over time. In particular, it decreased by about 20% in the period between 2016 and 2018 compared to 2007 for those in their 80s population. The trend of prevalence according to gender decreased significantly in women. According to the level of education, it showed the greatest decrease in the lowest group although the prevalence itself was higher than that of the upper education group. Conclusion: The prevalence of edentulism among Korean elder population has decreased over time 2007 from 12.8%. However, the concern on lower education group or men will be needed since those are still exposed to be in higher risk for edentulism.

5.
Int Wound J ; 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33733593

RESUMO

A hypertrophic scar is a common dermal fibroproliferative lesion usually treated with topical silicone. Verapamil, a type of calcium channel blocker, is considered a candidate drug for the treatment of hypertrophic scars. Here, we report that the addition of verapamil to topical silicone gel enhances treatment outcomes of hypertrophic scars. Upon creation of hypertrophic scars with the rabbit ear model, varying concentrations of verapamil-added silicone gel (0.1, 1, and 10 mg/g) were applied daily for 28 days. After the animals were euthanised, microscopic measurement was performed for (a) scar elevation index (SEI), (b) fibroblast count, and (c) capillary count. On gross analysis, features of hypertrophic scars were significantly alleviated in the verapamil-added groups. On histologic examination, verapamil-added groups showed (a) reduced SEI (1.93 (1.79-2.67) for control vs 1.34 (1.21-1.51) for silicone only and 1.13 (1.01-1.65) for verapamil-added silicone), (b) fibroblast count 700.5 (599.5-838.5) for control, 613.25 (461-762.5) for silicone only, and 347.33 (182.5-527) for verapamil-added silicone), and (c) capillary formation (52 (35.5-96.5) for control, 46 (28-64.5) for silicone only, and 39.83(24-70) for verapamil-added silicone) (Kruskal-Wallis test, P < .05). On western blot, expression levels of collagen I protein was lower in the 1 mg/g and 10 mg/g verapamil-added silicone compared with control. Therefore, we suggest a therapeutic concentration of verapamil-added silicone gel of at least over 1 mg/g. Further study regarding maximally effective concentration and deeper insight into the mechanism of action should follow.

6.
J Vet Sci ; 22(2): e21, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33774937

RESUMO

In this study, we describe the isolation and characterization of previously unreported Y280-lineage H9N2 viruses from two live bird markets in Korea in June 2020. Genetic analysis revealed that they were distinct from previous H9N2 viruses circulating in Korea and had highest homology to A/chicken/Shandong/1844/2019(H9N2) viruses. Their genetic constellation showed they belonged to genotype S, which is the predominant genotype in China since 2010, where genotype S viruses have infected humans and acted as internal gene donors to H5 and H7 zoonotic influenza viruses. Active surveillance and control measures need to be enhanced to protect the poultry industry and public health.

7.
Sci Total Environ ; 777: 146122, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33689889

RESUMO

It is believed that the generation of odorous materials in manure-slurry pits during the storage can be reduced by recirculating aerobically treated liquid fertilizer (ATLF) to a manure-pit recharge system (PRS). However, the biological mechanisms for reduction of those problematic compounds remain poorly understood. In this study, the links between microbial evolution and changes in chemical composition and odorous compounds were analyzed where swine-manure slurry was stored in a full-scale PRS. Some beneficial microorganisms were successfully established in the PRS. This resulted in the accumulation of fewer undesirable chemical components and lower amounts of odorous compounds compared to those in a conventional swine-manure slurry pit (the control). Decrease in the volatile fatty acids (1387-8478 mg/L â†’ 306-1258 mg/L) and NH3 (3387-4300 mg/L â†’ 85-200 mg/L) in the PRS was mainly due to the development of a key community that included a mix of aerobic, anaerobic fermentative, nitrifying (0.1-0.6%) and denitrifying (1.7-3.5%), and methanogenic microorganisms (2.1-4.2%). Meanwhile, the generation of greater amounts of H2S (12-290 mg/L â†’ 61-1754 mg/L) was found in the PRS, which condition was supported by the increased proportion of sulfate-reducing bacteria (0.5-3%). To the authors' best knowledge this is the first study comprehensively analyzing microbial dynamics linked with the reduction of odorous compounds in the full-scale PRS in response to recirculation of ATLF.

8.
Ying Yong Sheng Tai Xue Bao ; 32(3): 836-844, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33754548

RESUMO

To promote the application of lidar technology in estimating standing stocks of the typical conifer stands in Northeast China, i.e., spruce-fir forest, larch forest, Korean pine forest, Pinus sylvestris var. mongolica forest, we combined the point cloud data obtained by airborne lidar with the data of 800 ground plots and established models of standing stocks for the four conifer stands by stepwise regression and partial least square. Partial least squares method was better than stepwise regression method (R2=0.05-0.15, RRMSE=2.6%-4.2%). Among the three types of feature variables involved in modeling, height variable (selected for 26 times) is more important than others (selected for 12 times and 11 times, respectively). With respect to the accuracy of models established based on the means of the partial least square, they worked best for Korean pine forest (R2=0.79, RMSE=60.92, RRMSE=22.9%) and larch forest (R2=0.76, RMSE=28.39, RRMSE=25.8%), followed by spruce-fir forest (R2=0.81, RMSE=46.96, RRMSE=27.7%) and P. sylvestris var. mongolica forest (R2=0.50, RMSE=55.49, RRMSE=30.4%). This study provi-ded an effective way to estimate standing stocks of four typical conifer stands in Northeast China.


Assuntos
Larix , Pinus , Traqueófitas , China , Florestas , Árvores
9.
Sci Adv ; 7(4)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33523942

RESUMO

Accumulation of immune cells and activation of the pro-inflammatory transcription factor NF-κB in feto-maternal uterine tissues is a key feature of preterm birth (PTB) pathophysiology. Reduction of the fetal inflammatory response and NF-κB activation are key strategies to minimize infection-associated PTB. Therefore, we engineered extracellular vesicles (exosomes) to contain an NF-κB inhibitor, termed super-repressor (SR) IκBα. Treatment with SR exosomes (1 × 1010 per intraperitoneal injection) after lipopolysaccharide (LPS) challenge on gestation day 15 (E15) prolonged gestation by over 24 hours (PTB ≤ E18.5) and reduced maternal inflammation (n ≥ 4). Furthermore, using a transgenic model in which fetal tissues express the red fluorescent protein tdTomato while maternal tissues do not, we report that LPS-induced PTB in mice is associated with influx of fetal innate immune cells, not maternal, into feto-maternal uterine tissues. SR packaged in exosomes provides a stable and specific intervention for reducing the inflammatory response associated with PTB.

10.
Arch Gynecol Obstet ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33616705

RESUMO

OBJECTIVE: The purpose of this study was to explore the factors influencing the sexual quality of life of patients with cervical cancer who underwent radical hysterectomy. METHODS: This multicenter retrospective cohort study was conducted from June 2013 to June 2018 at nine hospitals in China. In total, 204 women diagnosed with stage IA to stage IIB cervical cancer who underwent radical hysterectomy completed the questionnaire. Sexual function was measured with the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ). All analyses were performed with R version 3.4.3 statistical software packages. A two-sided significance level of 0.05 was used to evaluate the statistical significance. RESULTS: The mean sexual quality of life score was 37.21 ± 17.28, where a higher PISQ score indicates a better sexual quality of life, and we identified the factors associated with sexual dysfunction. The average follow-up time was 29.0 ± 16.0 months. In addition to radical hysterectomy, 182 (89.2%) patients underwent ovarian suspension, 93 (45.6%) underwent chemotherapy, and 74 (36.3%) underwent concurrent radiotherapy. The univariate analysis confirmed that age represents a protective factor for sexual function (odds ratio (OR) 6.0, 95% confidence interval (CI) 1.1-10.8, p = 0.017). The patients who underwent ovarian suspension were more likely to experience a good sexual quality of life (OR - 7.2, 95% CI [- 14.8, - 0.4], p = 0.035) compared to those who did not undergo ovarian suspension. A significant negative association was observed between radiotherapy and the behavioral-emotive, physical and partner-related domains of the PISQ (behavioral-emotive, OR - 1.5, 95% CI [- 2.6, - 0.4], p = 0.011; physical, OR - 0.9, 95% CI [- 1.5, - 0.3], p = 0.006; partner-related, OR - 0.7, 95% CI [- 1.3, 0.0], p = 0.043). Chemotherapy and radiotherapy were common risk factors for sexual dysfunction, and radiotherapy exerted a stronger effect than chemotherapy. CONCLUSIONS: This study shows that the sexual function of cervical cancer patients tends to be related to age, radiotherapy, and chemotherapy. However, across these factors, patients with preserved ovaries tend to return to a satisfactory sexual quality of life after recovering from surgery.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33447913

RESUMO

At present, it has been noticed that some patients recovered from COVID-19 present a recurrent positive RNA test of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) after being discharged from hospitals. The purpose of the current study was to characterize the clinical features of re-hospitalized patients with recurrent SARS-CoV-2 positive results. From January 12 to April 1 of 2020, our retrospective study was conducted in China. The exposure history, baseline data, laboratory findings, therapeutic schedule, and clinical endpoints of the patients were collected. All the patients were followed until April 10, 2020. Among all COVID-19 patients included in the current study, there were 14 re-hospitalized patients due to recurrent positive tests of SARS-CoV-2 RNA. Fever (11 [78.6%]), cough (10 [71.4%]), and fatigue (7 [50.0%]) were the most common symptoms on the patient's first admission, and less symptoms were found on their second admission. The average duration from the onset of symptoms to admission to hospital was found to be 8.4 days for the first admission and 2.6 days for the second admission (P = 0.002). The average time from the detection of RNA (+) to hospitalization was 1.9 days for the first admission and 2.6 days for the second admission (P = 0.479), and the average time from RNA (+) to RNA (-) was 11.1 days for the first admission and 6.3 days for the second admission (P = 0.030). Moreover, the total time in hospital was 18.6 days for the first admission and 8.0 days for the second admission (P = 0.000). It may be necessary to increase the isolation observation time and RT-PCR tests should be timely performed on multiple samples as soon as possible.

12.
J Neural Transm (Vienna) ; 128(2): 181-189, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33507401

RESUMO

A wearable sensor system is available for monitoring of bradykinesia in patients with Parkinson's disease (PD), however, it remains unclear whether kinematic parameters would reflect clinical severity of PD, or would help clinical diagnosis of physicians. The present study investigated whether the classification model using kinematic parameters from the wearable sensor may show accordance with clinical rating and diagnosis in PD patients. Using the Inertial Measurement Units (IMU) sensor, we measured the movement of finger tapping (FT), hand movements (HM), and rapid alternating movements (RA) in 25 PD patients and 21 healthy controls. Through the analysis of the measured signal, 11 objective features were derived. In addition, a clinician who specializes in movement disorders viewed the test video and evaluated each of the Unified Parkinson's Disease Rating Scale (UPDRS) scores. In all items of FT, HM, RA, the correlation between the linear regression score obtained through objective features (angle, period, coefficient variances for angle and period, change rates of angle and period, angular velocity, total angle, frequency, magnitude, and frequency × magnitude) and the clinician's UPDRS score was analyzed, and there was a significant correlation (rho > 0.7, p < 0.001). PD patients and controls were classified by deep learning using objective features. As a result, it showed a high performance with an area under the curve (AUC) about as high as 0.9 (FT Total = 0.950, HM Total = 0.889, RA Total = 0.888, ALL Total = 0.926. This showed similar performance to the classification result of binary logistic regression and neurologist, and significantly higher than that of family medicine specialists. Our results suggest that the deep learning model using objective features from the IMU sensor can be usefully used to identify and evaluate bradykinesia, especially for general physicians not specializing in neurology.

13.
Stem Cell Res Ther ; 12(1): 3, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407888

RESUMO

BACKGROUND: Although pancreatic islet transplantation therapy is ideal for diabetes patients, several hurdles have prevented it from becoming a standard treatment, including donor shortage and low engraftment efficacy. In this study, we prepared insulin-producing cells trans-differentiated from adult human liver cells as a new islet source. Also, cell sheet formation could improve differentiation efficiency and graft survival. METHODS: Liver cells were expanded in vitro and trans-differentiated to IPCs using adenovirus vectors carrying human genes for PDX1, NEUROD1, and MAFA. IPCs were seeded on temperature-responsive culture dishes to form cell sheets. Differentiation efficiency was confirmed by ß cell-specific gene expression, insulin production, and immunohistochemistry. IPC suspension was injected by portal vein (PV), and IPC sheet was transplanted on the liver surface of the diabetic nude mouse. The therapeutic effect of IPC sheet was evaluated by comparing blood glucose control, weight gain, histological evaluation, and hepatotoxicity with IPC injection group. Also, cell biodistribution was assessed by in vivo/ex vivo fluorescence image tagging. RESULTS: Insulin gene expression and protein production were significantly increased on IPC sheets compared with those in IPCs cultured on conventional culture dishes. Transplanted IPC sheets displayed significantly higher engraftment efficiency and fewer transplanted cells in other organs than injected IPCs, and also lower liver toxicity, improved blood glucose levels, and weight gain. Immunohistochemical analyses of liver tissue revealed positive staining for PDX1 and insulin at 1, 2, and 4 weeks after IPC transplantation. CONCLUSIONS: In conclusion, cell sheet formation enhanced the differentiation function and maturation of IPCs in vitro. Additionally, parameters for clinical application such as distribution, therapeutic efficacy, and toxicity were favorable. The cell sheet technique may be used with IPCs derived from various cell sources in clinical applications.

14.
Mol Cells ; 44(1): 38-49, 2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-33510050

RESUMO

Airway mucus secretion is an essential innate immune response for host protection. However, overproduction and hypersecretion of mucus, mainly composed of the gel- forming MUC5AC protein, are significant risk factors for patients with asthma and chronic obstructive pulmonary disease (COPD). The transforming growth factor ß (TGFß) signaling pathway negatively regulates MUC5AC expression; however, the underlying molecular mechanism is not fully understood. Here, we showed that TGFß significantly reduces the expression of MUC5AC mRNA and its protein in NCI-H292 cells, a human mucoepidermoid carcinoma cell line. This reduced MUC5AC expression was restored by a TGFß receptor inhibitor (SB431542), but not by the inhibition of NF-κB (BAY11-7082 or Triptolide) or PI3K (LY294002) activities. TGFß-activated Smad3 dose-dependently bound to MUC5AC promoter. Notably, TGFß-activated Smad3 recruited HDAC2 and facilitated nuclear translocation of HDAC2, thereby inducing the deacetylation of NF-κB at K310, which is essential for a reduction in NF-κB transcriptional activity. Both TGFß-induced nuclear translocation of Smad3/HDAC2 and deacetylation of NF-κB at K310 were suppressed by a Smad3 inhibitor (SIS3). These results suggest that the TGFß-activated Smad3/HDAC2 complex is an essential negative regulator for MUC5AC expression and an epigenetic regulator for NF-κB acetylation. Therefore, these results collectively suggest that modulation of the TGFß1/Smad3/HDAC2/NF-κB pathway axis can be a promising way to improve lung function as a treatment strategy for asthma and COPD.

15.
Biochim Biophys Acta Mol Basis Dis ; 1867(5): 166084, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33497821

RESUMO

In osteoporosis, mesenchymal stem cells (MSCs) prefer to differentiate into adipocytes at the expense of osteoblasts. Although the balance between adipogenesis and osteogenesis has been closely examined, the mechanism of commitment determination switch is unknown. Here we demonstrate that phospholipase D1 (PLD1) plays a key switch in determining the balance between bone and fat mass. Ablation of Pld1 reduced bone mass but increased fat in mice. Mechanistically, Pld1/- MSCs inhibited osteoblast differentiaion with diminished Runx2 expression, while osteoclast differentiation was accelerated in Pld1-/- bone marrow-derived macrophages. Pld1-/- osteoblasts showed decreased expression of osteogenic makers. Increased number and resorption activity of osteoclasts in Pld1-/- mice were corroborated with upregulation of osteoclastogenic markers. Moreover, Pld1-/- osteoblasts reduced ß-catenin mediated-osteoprotegerin (OPG) with increased RANKL/OPG ratio which resulted in accelerated osteoclast differentiation. Thus, low bone mass with upregulated osteoclasts could be due to the contribution of both osteoblasts and osteoclasts during bone remodeling. Moreover, ablation of Pld1 further increased bone loss in ovariectomized mice, suggesting that PLD1 is a negative regulator of osteoclastogenesis. Furthermore, loss of PLD1 increased adipogenesis, body fat mass, and hepatic steatosis along with upregulation of PPAR-γ and C/EBPα. Interestingly, adipocyte-specific Pld1 transgenic mice rescued the compromised phenotypes of fat mass and adipogenesis in Pld1 knockout mice. Collectively, PLD1 regulated the bifurcating pathways of mesenchymal cell lineage into increased osteogenesis and decreased adipogenesis, which uncovered a previously unrecognized role of PLD1 in homeostasis between bone and fat mass.

16.
Int J Clin Oncol ; 26(3): 532-542, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33387087

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer in the worldwide. Sorafenib is approved for first-line therapy against advanced HCC, but chemo-resistance is still a leading cause of tumor relapse and treatment failure in HCC. Thus, there is a significant clinical need to identify effective strategies to overcome drug resistance on the disease. METHODS: The protein and mRNA expression of TRIM37 in HCC cell lines and patient tissues were determined using Real-time PCR and Western blot, respectively. HCC tissue samples were analyzed by IHC to investigate the association between TRIM37expression and the clinicopathological characteristics of HCC patients. Functional assays, such as MTT, FACS, and Tunel assay, are used to determine the oncogenic role of TRIM37 in human HCC progression. Furthermore, western blotting and luciferase assay were used to determine the mechanism of TRIM37promotes chemoresistance in HCC. RESULTS: We found that both the mRNA and protein expression of TRIM37 was markedly upregulated in HCC cell lines and tissues, especially in Sorafenib-resistance HCC tissues. Moreover, high TRIM37 expression was associated with poor prognosis with HCC patients. TRIM37 overexpression confers Sorafenib resistance on HCC cells; however, inhibition of TRIM37 sensitized HCC cell lines to Sorafenib cytotoxicity. Additionally, TRIM37 upregulated the levels of AKT activity and phosphorylated AKT, thereby activating canonical AKT signaling. CONCLUSION: Our findings suggest that targeting TRIM37 signaling may represent a promising strategy to enhance Sorafenib response in HCC patients with chemoresistant.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases
17.
Int J Mol Sci ; 22(2)2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33445732

RESUMO

Cathepsin K (CTSK) is a cysteine protease that is mainly produced from mature osteoclasts and contributes to the destruction of connective tissues and mineralized matrix as a consequence of periodontal disease (PD). However, few studies have reported its regulatory role in osteoclastogenesis-supporting cells in inflammatory conditions. Here, we investigated the role of CTSK in osteoclastogenesis-supporting cells, focusing on the modulation of paracrine function. Microarray data showed that CTSK was upregulated in PD patients compared with healthy individuals, which was further supported by immunohistochemistry and qPCR analyses performed with human gingival tissues. The expression of CTSK in the osteoclastogenesis-supporting cells, including dental pulp stem cells, gingival fibroblasts, and periodontal ligament fibroblasts (PDLFs) was significantly elevated by treatment with inflammatory cytokines such as TNFα and IL-1ß. Moreover, TNFα stimulation potentiated the PDLF-mediated osteoclastogenesis of bone marrow-derived macrophages. Interestingly, small interfering RNA-mediated silencing of CTSK in PDLF noticeably attenuated the TNFα-triggered upregulation of receptor activator of nuclear factor kappa-B ligand (RANKL), macrophage colony-stimulating factor, and RANKL/osteoprotegerin ratio, thereby abrogating the enhanced osteoclastogenesis-supporting activity of PDLF. Collectively, these results suggest a novel role of CTSK in the paracrine function of osteoclastogenesis-supporting cells in periodontal disease.


Assuntos
Catepsina K/metabolismo , Citocinas/metabolismo , Fibroblastos/metabolismo , Osteoclastos/metabolismo , Osteogênese/fisiologia , Comunicação Parácrina/fisiologia , Doenças Periodontais/metabolismo , Ligamento Periodontal/metabolismo , Animais , Células Cultivadas , Gengiva/metabolismo , Humanos , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Fator Estimulador de Colônias de Macrófagos/metabolismo , Camundongos Endogâmicos ICR , Ligante RANK/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
18.
Tissue Eng Regen Med ; 18(1): 179-186, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33515165

RESUMO

BACKGROUND: Verapamil is used in the treatment of hypertension, angina pectoris, cardiac arrhythmia, hypertrophic scars, and keloids to block transmembrane calcium ion flux. Verapamil has antioxidant activity, which enhances the production of nitric oxide (NO). NO promotes the proliferation of fibroblasts, keratinocytes, endothelial cells, and epithelial cells during wound healing. In this study, we investigated the effect of verapamil and its antioxidant properties on the enhancement of acute wound healing via NO. METHODS: A full-thickness wound healing model was created on the rat dorsal with a silicone ring. The wound closure rate was estimated every 2 days for 14 days. A histological study was performed to evaluate wound healing. Immunofluorescence staining was analyzed for angiogenesis. The expressions of collagen type I (COL I), collagen type III (COL III), and vascular endothelial growth factor (VEGF) were assessed by Western blot. Real-time polymerase chain reaction (qRT-PCR) was performed to examine the expression of endothelial NO synthase and inducible NO synthase, which are related to antioxidant activity in the process of wound healing. RESULTS: The wound closure rate was faster in the verapamil group compared to the control and silicone groups. Histologic analysis revealed capillaries and stratum basale in the verapamil group. Immunofluorescence staining was shown vessel formation in the verapamil group. Western blot and qRT-PCR analysis revealed high expression levels of COL I, VEGF, eNOS, and FGF in the verapamil. CONCLUSION: Verapamil's antioxidant activity enhances NO production in acute wound healing. We suggest that verapamil can be used to promote acute wound healing.

19.
J Proteomics ; 231: 103995, 2021 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-33011346

RESUMO

Diarrheal irritable bowel syndrome (IBS-D) is a chronic functional bowel disease with no clear diagnostic markers and no satisfactory treatment strategies. In recent years, the importance of intestinal microstructure and function in IBS-D has been emphasized. However, the intestinal tissue proteomics of IBS-D patients has not been analyzed. Here, we systematically analyzed the molecule profiling of the intestinal tissues in IBS-D patients through tandem mass tag (TMT)-based proteomics for the first time, aiming to reveal the pathogenesis and provide evidence for diagnosis and treatment of IBS-D. Five IBS-D patients and five healthy subjects were selected, biopsy tissue samples from the junction of sigmoid and rectum were analyzed by TMT proteomics. Differentially expressed proteins were obtained and bioinformatics analysis was performed. Furthermore, parallel reaction monitoring (PRM) and q-PCR detection were applied to validate the differentially expressed proteins. Eighty differentially expressed proteins were screened, 48 of which were up-regulated and 32 were down-regulated (fold change >1.2, P < 0.05). Bioinformatics analysis showed that these proteins were significantly enriched in the nutrient ingestion pathways which are related to immune molecules. SELENBP1, VSIG2, HMGB1, DHCR7, BCAP31 and other molecules were significantly changed. Our study revealed the underlying mechanisms of IBS-D intestinal dysfunction. SIGNIFICANCE: Irritable bowel syndrome with diarrhea (IBS-D) is a worldwide chronic intestinal disease with no definite diagnostic markers. It is still a challenge to accurately locate the pathogenesis of patients for appropriate treatment strategy. Established proteomics studies of IBS-D are only based on urine, blood, or tissue samples from animals. Our study was the first TMT proteomics analysis on intestinal biopsy tissues of patients with IBS-D, which revealed the changes of molecular spectrum of actual intestinal conditions in patients with IBS-D. Some important molecules and signaling pathways have been found abnormal in our study, which were related with nutrient uptake. They not only provided preliminary clues for low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) intolerance, an unsolved conundrum of IBS-D, but also revealed obscure problems of protein, lipid, and other nutrients ingestion in IBS-D patients. Some of these differentially expressed molecules have been preliminarily verified, and will may be potential candidate molecules for diagnostic markers of IBS-D.

20.
J Cell Physiol ; 236(1): 549-560, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32869317

RESUMO

Glioblastoma (GBM) is an aggressive brain tumor and drug resistance remains a major barrier for therapeutics. Epigenetic alterations are implicated in GBM pathogenesis, and epigenetic modulators including histone deacetylase (HDAC) inhibitors are exploited as promising anticancer therapies. Here, we demonstrate that phospholipase D1 (PLD1) is a transcriptional target of HDAC inhibitors and confers resistance to HDAC inhibitor in GBM. Treatment of vorinostat upregulates PLD1 through PKCζ-Sp1 axis. Vorinostat induces dynamic changes in the chromatin structure and transcriptional machinery associated with PLD1 promoter region. Cotreatment of vorinostat with PLD1 inhibitor further attenuates invasion, angiogenesis, colony-forming capacity, and self-renewal capacity, compared with those of either treatment. PLD1 inhibitor overcomes resistance to vorinostat in GBM cells intracranial GBM tumors. Our finding provides new insight into the role of PLD1 as a target of resistance to vorinostat, and PLD1 inhibitor might provide the basis for therapeutic combinations with improved efficacy of HDAC inhibitor.

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