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1.
J Ovarian Res ; 13(1): 29, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32183851

RESUMO

BACKGROUND: Olaparib, a poly ADP-ribose polymerase (PARP) inhibitor, has proven to be effective and safe as maintenance therapy and multiline therapy in ovarian cancer, especially in patients with BRCA mutations. This study intended to observe the influence of tumor load on the efficacy and safety of olaparib in recurrent ovarian cancer. CASES PRESENTATION: Three patients harbored gBRCAwt with low tumor load (LTL), while two women harbored BRCAmt with high tumor load (HTL) were recruited. Two of the three LTL patients achieved partial response, and the other showed stable disease. Both HTL patients were assessed to have progressive disease in a short time. Olaparib appears to be effective and safe for LTL recurrent ovarian cancer patients even if it is gBRCAwt, while the response is poor in HTL patients. CONCLUSIONS: Tumor load may be another potential marker to predict the effect of PARP inhibitors. The present head-to-head observational series provides new evidence on this issue for further research from bench to bedside in the future.

2.
Int J Hematol ; 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32162095

RESUMO

Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs) represent a promising treatment option for EBV-associated post-transplantation lymphoproliferative disorders (PTLD). However, production of EBV-CTLs is often complicated and expensive. In the present study, we sought to establish an easy-to-use and economical production protocol for EBV-CTLs. EBV-CTLs were generated using latent membrane protein 1 (LMP1) peptides based on a modified generation protocol of cytokine-induced killer (CIK) cells. After 2-week culture, cells were well expanded (median total cell number: 9.82 × 109; median expansion fold: 107.8) and the median EBV LMP1-specific CD8+ T cell number was 8.94 × 108 (median frequency: 6.7%). However, the EBV-CTL products, unlike CIK cells, did not exhibit NK-like anti-tumor activity. Furthermore, the clinical efficacy of EBV-CTLs was demonstrated with a successful treatment of PTLD on a compassionate use basis in a patient following haploidentical hematopoietic stem cell transplantation. This study indicates the safety and efficacy of EBV LMP1-specific CTLs generated based on a modified generation protocol of CIK cells. Further investigation in a well-designed clinical study is warranted.

3.
Trials ; 21(1): 264, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32171318

RESUMO

INTRODUCTION: Knee osteoarthritis (KOA) is a chronic disease with symptoms of persistent pain or resting pain, joint stiffness, numbness, limitation of activity and even disability, with significant associated costs and effects on individuals' life quality. The use of acupuncture for the management of chronic pain is receiving increasing recognition from both the public and professionals. The aim of this study is to identify the effects of three commonly used acupuncture treatments for KOA. METHODS/ANALYSIS: In a prospective trial involving six hospitals in Zhejiang Province (China), 360 patients with KOA will be included. Eligible patients will be randomized into six groups: Acupuncture, Electro-acupuncture, Mild moxibustion, Warm-needling, Sham acupuncture and Celebrex treatment. Twelve treatment sessions will be performed over a 4-week period. The primary outcome will be the visual analogue scale and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function scores (the average of the past 3 days) at weeks 2 and 4 and at 3-month and 6-month follow-up. Secondary outcome measures will be as follows: the WOMAC pain score and WOMAC stiffness score (the average of the past 3 days); the Physical Activity Scale of the Elderly (PASE); knee joint swelling measurement; the WHO Quality Of Life-BREF (WHOQOL-BREF) life quality scale; and the incidence of adverse events. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03563690. Registered on 2rd July 2018.

4.
Eur J Dent Educ ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32052542

RESUMO

OBJECTIVE: To evaluate the effectiveness of the periodontal continuing educational delivery mode via a periodontal alliance. METHODS: An innovative continuing educational delivery mode via a periodontal alliance has been conducted using a periodontal alliance of 30 hospitals in 18 provinces of China. This delivery mode integrates several instructional methods, including lectures, case presentations, and interactive question and answer sessions, all of which were conducted through online platforms. The effectiveness of the mode was evaluated via a questionnaire that was administered to the participants. The questionnaire consisted of 13 closed-ended questions and 2 open-ended questions. RESULTS: Of the 450 participants, 343 (76%) returned the questionnaire. Of the returned surveys, more than 92% provided positive feedback regarding the instructional methods of the program, stating that the techniques helped them study more efficiently and saved them time and money. More than 85% of the participants were satisfied with the instructional content and more than 90% of the participants considered the educational value of the program to be high, as it helped them identify gaps in knowledge, promoted their ability to establish treatment plans, and encouraged them to network with one another and thereby establish a supportive environment. With respect to the responses to the open-ended questions, the participants claimed that the most useful aspects of the program were related to time and cost savings. The most frequent feedback with respect to improving the program was to include hands-on courses and to divide the program into different levels. CONCLUSIONS: The participants responded positively to the program. The periodontal alliance delivery mode was determined to be an effective way to improve the quality of continuing dental education.

5.
FEBS Open Bio ; 10(3): 362-370, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31930721

RESUMO

Chronic fluoride exposure from drinking water may result in endemic fluorosis. To better understand the mechanisms by which some people are resistant to fluorosis, here we investigated the effect of treatment with NaF (sodium fluoride) on production of reactive oxygen species (ROS), morphological changes in mitochondria, the mRNA expression of Fas ligand (Fas-L), and the protein expression of cleaved caspase-3 in regular L-929 cells and fluoride-resistant (FR) L-929 cells. While morphological changes indicative of apoptosis and a network of fragmented mitochondria were observed in regular L-929 cells after NaF treatment, there were no morphological changes in FR L-929 cells after NaF treatment. Treatment with 10 mm NaF induced a significant difference in the production of ROS, triggered the expression of cleaved caspase-3, and upregulated the mRNA expression of Fas-L in regular L-929 cells. However, there was no significant production of ROS in FR L-929 cells. Additionally, cleaved caspase-3 and upregulated Fas-L were not detected in FR L-929 cells. These results suggest that FR fibroblasts are resistant to oxidative stress and apoptosis induced by fluoride.

6.
Cancer Epidemiol Biomarkers Prev ; 29(2): 487-492, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31748259

RESUMO

BACKGROUND: The association of plasma homocysteine level (PHL) with gastric cancer risk was reported in observational studies. However, the causality is challenging due to confounding factors and the lack of evidence from well-designed cohort studies. Herein, we performed a two-sample Mendelian randomization (MR) analysis to investigate whether PHL is causally related to gastric cancer risk. METHODS: We performed the MR analysis based on the results from genome-wide association studies consisting of 2,631 patients with gastric cancer and 4,373 controls. An externally weighted genetic risk score (wGRS) was constructed with 15 SNPs with well-established associations with PHL. We utilized logistic regression model to estimate associations of PHL-related SNPs and wGRS with gastric cancer risk in total population and in strata by sex, age, and study site, in addition to a series of sensitivity analyses. RESULTS: High genetically predicted PHL was associated with an increased gastric cancer risk (per SD increase in the wGRS: OR = 1.07; 95% confidence interval, 1.01-1.12; P = 0.011), which was consistent in sensitivity analyses. Subgroup analyses provided evidence of a stronger association with gastric cancer risk in women than in men. MR-Egger and weighted median regression suggested that potentially unknown pleiotropic effects were not biasing the association between PHL and gastric cancer risk. CONCLUSIONS: These results revealed that genetically predicted high PHL was associated with an increased gastric cancer risk, suggesting that high PHL may have a causal role in the etiology of gastric cancer. IMPACT: These findings provide causal inference for PHL on gastric cancer risk, suggesting a causal role of high PHL in the etiology of gastric cancer.

7.
Exp Appl Acarol ; 80(1): 17-27, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31828556

RESUMO

Demographic analysis of Tetranychus urticae under photoperiods of 12L:12D, 14L:10D and 18L:6D at 75% relative humidity and 25 °C showed that the developmental time and oviposition per female declined with increasing light period. The nymph, oviposition and adult stages were significantly shortened, resulting in shorter generation duration and faster population decline, but there was no effect on egg and larval stages of T. urticae. Kaplan-Meier survival analysis followed by a log-rank test indicated that the mean and median survival times were 40.4 (12:12), 39.1 (14:10), and 38.1 (18:6) days, and 42.0, 40.0, 39.0 days, respectively-this difference among photoperiods was significant. The total number of eggs per female under the three photoperiods was 69.63 (12:12), 77.44 (14:10) and 42.17 (18:6), respectively, and the sex ratios were 70.0, 81.6 and 71.6% female offspring. Under 14 h light, T. urticae experienced its highest net reproductive rate (R0 = 83.0577), intrinsic rate of increase (rm = 0.2740), finite rate of increase (λ = 1.3153), lowest mean generation time (T = 16.1277 days) and population doubling time (Dt = 2.5294 days). All demographic parameters displayed a decreasing relationship with the light phase under the three photoperiods. No significant difference in susceptibilities to the acaricides diafenthiuron and propargite was shown among the three photoperiods. The results of this study indicated that the 14L:10D photoperiod was optimal for the development and reproduction of T. urticae, and the 18L:6D period was disadvantageous for spider mite development.

8.
Front Neurosci ; 13: 1225, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31798406

RESUMO

Aim: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive and safe technique for treatment of central and peripheral nerve injury. In recent years, this technique has been widely used in clinic, and an increasing number of studies have reported its mechanisms. In this study, we investigated the mechanisms of rTMS-mediated autophagy flux in human bone mesenchymal stromal cells (BMSCs). Methods: A frequency of 50 Hz was employed. Cells were divided into five groups: (1) normal, (2) sham, (3) 0.5 T, (4) 1.0 T, and (5) 1.5 T. Cells were stimulated for 20 min/day. The levels of p62, LC3-II/I, phosphorylated extracellular signal-regulated kinase (p-ERK), ERK, phosphorylated-AKT (p-AKT), AKT, phosphorylated mammalian target of rapamycin (p-mTOR), mTOR, phosphorylated protein kinase A (p-PKA), PKA, phosphorylated epidermal growth factor receptor (p-EGFR), EGFR, Nanog, Oct4, Sox2, and NMDA receptor (NMDAR1) were investigated by western blotting. Intracellular calcium (Ca2+) levels were quantified by flow cytometry. p62 and LC3 expression was also assessed by immunofluorescence analysis. Results: In the 0.5 T group, rTMS increased the expression of LC3-II/I, p-ERK/ERK, and NMDAR1 and decreased the levels of p62 and p-mTOR/mTOR than in the normal group. The ratio of p-AKT/AKT, p-PKA/PKA, and p-EGFR/EGFR and the expression of Nanog, Oct4, and Sox2 remained unchanged. Immunofluorescence analysis revealed colocalization of p62 with LC3 puncta, and flow cytometry analysis displayed that Ca2+ levels were elevated. However, in the 1.0 and 1.5 T groups, no changes in the expression of these autophagy markers were observed. Conclusion: In the 0.5 T group, high-frequency rTMS can induce autophagy through NMDAR-Ca2+-ERK-mTOR signaling in BMSCs. In the 1.0 and 1.5 T groups, autophagy is not activated.

9.
Leuk Lymphoma ; : 1-6, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31858854

RESUMO

Hematological toxicity is a common adverse effect of tyrosine kinase inhibitors (TKIs) for the treatment of chronic myeloid leukemia (CML). We retrospectively investigated the incidence of hematological toxicity after TKI administration in 143 CML patients and parameters associated with hematological toxicity. Severe hematological toxicity (grade 3-4) existed in 26 (18.2%) patients. Marrow fibrosis (MF), age, Sokal score, and spleen enlargement were associated with severe hematological toxicity. Further multivariate analysis showed that only MF was an independent predictor. Complete cytogenetic response(CCyR) rates and major molecular response (MMR) rates with grade 3-4 hematological toxicity were 42.3% and 26.9%, respectively, significantly lower than patients with grade 1-2 and without hematological toxicity (p = .032 for CCyR and p = .044 for MMR). Similar results were observed regarding progression-free survival (PFS) and overall survival (OS) (p = .011 for PFS and p = .037 for OS). This study indicated that MF was an independent predictor of severe hematological toxicity of TKIs.

10.
Gen Psychiatr ; 32(5): e100028, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31673674

RESUMO

The population of early-onset Alzheimer's disease (EOAD) accounts for 1%-2% of the total population of Alzheimer's disease, and genetic mutations are more common in EOAD. The first symptom of the patient in the present case report was the decline in memories of recent events, and the disease progressed rapidly in the following 2 years. Genetic testing has revealed the presence of genetic mutations (c.A479G, p.N160S) of ACE, which causes the 160th codon of the ACE protein to change from aspartic acid to serine, and at the same time genotype of apolipoprotein E (APOE) is ɛ3/ɛ4. We think that this patient carries the mutation type of the sensitive gene ACE and the risk gene APOE of Alzheimer's disease, and this is the reason why the disease progressed rapidly. Moreover, we discussed ACE genetic mutation's meaning in EOAD progression.

11.
J Ovarian Res ; 12(1): 117, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31775908

RESUMO

PURPOSE: Poly (ADP-ribose) polymerase (PARP) inhibitor, is a milestone in treatment of ovarian cancer. However, there is no real world study from China regarding the clinical outcome of the taking PARP inhibitor (PARPi), Olaparib(Lynparza™). The goal of this research is to evaluate the side effects and short-term efficacy in advanced ovarian cancer patients who administered Olaparib. METHODS: Patients with ovarian cancer, fallopian tube cancer and peritoneal cancer that treated with Olaparib in The Affiliated Cancer Hospital of Nanjing Medical University between September 2018 and June 2019 were recruited. The drug associated Adverse Events (AEs) were collected and short-term efficacy were analyzed by modified Response Evaluation Criteria in Solid Tumors (mRECIST) . RESULTS: Of all 28 enrolled patients, 92.9% were ovarian cancer, 7.1% were fallopian tube cancer, and 39.3% cases harbored germline BRCA-mutation. There were 6(21.4%) patients received Olaparib after multi-line chemotherapy, and 10 patients (35.7%) as second-line maintenance therapy and 2 patients (7.1%) as first-line maintenance therapy. There were still other 10 cases (35.7%) received Olaparib as exploratory therapy. Abdominal distention, decreased blood pressure, increased body hair, thirsty, burning sensation of stomach and leg swelling were newly reported AEs. Serious Adverse Events(SAEs) were usually managed by dose interruption or dose reduction, rather than discontinuation. 3 patients discontinued treatment, 8 patients received reduced dose of Olaparib, and 4 patients stopped therapy after the alleviation of AEs. Of all 28 enrolled cases, in monotherapy group, 1 of 6 patients achieved stable disease(SD) and also 2 patients achieved stable disease(SD) combined with anti-angiogenic drugs when disease progressed. 2 patients achieved complete remission(CR) and 3 patients were stable with exploratory therapy. CONCLUSIONS: The AEs of Olaparib were all manageable. For the first time, we also identified several AEs such as abdominal distention, decreased blood pressure, increased body hair, thirsty, burning sensation of stomach and leg swelling during the follow-up which have not been reported. The short-term efficacy was observed in some exploratory cases that provided new potential indication to PARPi-related clinical trials.

12.
J Transl Med ; 17(1): 343, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619254

RESUMO

BACKGROUND: Liver cancer is the second leading causes of cancer-related death globally. Pyrroline-5-carboxylate reductase 1 (PYCR1) plays a critical role in metabolic profiles of tumors. Therefore, it is necessary to explore the mechanisms of PYCR1 on cell growth and survival in hepatocellular carcinoma (HCC). METHODS: Protein and mRNA expression levels of PYCR1 in 140 pairs of tumor and adjacent normal liver tissues of HCC patients were analyzed by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). Expressions of PYCR1 were inhibited in BEL-7404 cells and SMMC-7721 cells using gene interference technology. The cell proliferation was detected by Celigo and MTT assay. The colony formation assay was also performed. The cell apoptosis was measured by flow cytometric assay. The effect of PYCR1 interference on tumor growth was observed by xenograft nude mice assay in vivo. The downstream pathway of PYCR1 interference was searched by microarray and bioinformatics analysis, and validated by qRT-PCR and western blot. RESULTS: PYCR1 levels were significantly up-regulated in HCC tumor tissues than adjacent normal liver tissues in both protein and mRNA levels (P < 0.01). In vitro, the cell proliferation was significantly slower in shPYCR1 group than shCtrl group in BEL-7404 and SMMC-7721 cells (P < 0.001). The colony number was significantly smaller after PYCR1 interference (P < 0.01). The percentage of apoptosis cells significantly increased in shPYCR1 group (P < 0.01). In vivo, PYCR1 interference could obviously suppress tumor growth in xenograft nude mice. The volume and weight of tumors were significantly smaller via PYCR1 interference. The c-Jun N-terminal kinase (JNK) signaling pathway significantly altered, and insulin receptor substrate 1 (IRS1) were significantly down-regulated by PYCR1 interference in both mRNA and protein levels (P < 0.001). CONCLUSION: PYCR1 interference could inhibit cell proliferation and promote cell apoptosis in HCC through regluting JNK/IRS1 pathway. Our study will provide a drug target for HCC therapy and a potential biomarker for its diagnosis or prognosis.

13.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(9): 876-880, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31506145

RESUMO

OBJECTIVE: To study the correlation of Mycoplasma pneumoniae DNA (MP-DNA) replication level in throat swab and bronchoalveolar lavage fluid (BALF) with disease severity in children with severe Mycoplasma pneumoniae pneumonia (SMPP). METHODS: A total of 44 children with SMPP who underwent bronchoalveolar lavage were enrolled as subjects. The serum levels of cytokines and MP-DNA replication times in throat swab were measured in the acute stage and the recovery stage, and the levels of interleukin (IL)-8 and MP-DNA replication times in BALF were measured in the acute stage. According to whether mechanical ventilation was needed for respiratory failure, the children were divided into a mechanical ventilation group (n=19) and a non-mechanical ventilation group (n=25), and the two groups were compared in MP-DNA replication times in BALF. RESULTS: For the children with SMPP, serum levels of C-reactive protein, erythrocyte sedimentation rate, lactate dehydrogenase, IL-1, IL-6, IL-8, and IL-18 in the acute stage were significantly higher than those in the recovery stage (P<0.05). In the acute stage, MP-DNA replication times in throat swab were positively correlated with those in BALF (r=0.613, P<0.05), and MP-DNA replication times in BALF were positively correlated with IL-18 levels in peripheral blood and BALF (r=0.613 and 0.41 respectively, P<0.05). Compared with the non-mechanical ventilation group, the mechanical ventilation group had significantly higher MP-DNA replication times in BALF, a significantly longer duration of systemic hormone treatment, significantly higher serum levels of lactate dehydrogenase and IL-18, and significantly higher white blood cell count and IL-18 level in BALF (P<0.05). CONCLUSIONS: In children with SMPP, MP-DNA replication level in throat swab and BALF can be used as a reference index for the assessment of disease severity.


Assuntos
Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Líquido da Lavagem Broncoalveolar , Criança , Citocinas , Replicação do DNA , DNA Bacteriano , Humanos
14.
Mol Med Rep ; 20(4): 3874-3882, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485646

RESUMO

Liver cancer is a one of the most frequent types of tumor worldwide. It has long been recognized that microRNAs are important participants in the progression of various types of cancer. The present study explored the role of microRNA­373 (miR­373) in liver cancer development. Reverse transcription­quantitative polymerase chain reaction was performed to evaluate the transcription level of miR­373 in 96 liver cancer tissues and adjacent normal liver tissues. The association of miR­373 with clinicopathological characteristics was analyzed using the χ2 test. Kaplan­Meier univariate analysis and multivariate hazard analysis were performed to identify the clinical potential of miR­373 in the prognosis of liver cancer patients. Transfection of miR­373 mimics into Hep3B and HepG2 liver cancer cell lines was conducted to reveal the underlying mechanism in regulating liver cancer progression. The functional assays included proliferation, migration, invasion and luciferase assays. The findings of the present study demonstrated that miR­373 transcription level was markedly downregulated in liver cancer tissues compared with the adjacent normal tissues and was associated with the clinical prognosis of liver cancer patients. Overexpressing miR­373 mimics in liver cancer cell lines decreased cell proliferation and invasion, suggesting that miR­373 exerts anti­tumor effects in liver cancer. In addition, data from the present study demonstrated the direct effect of miR373 on inhibiting the expression and signaling of Ras­related protein Rab22a, a well­known oncoprotein. Taken together, the results from the present study suggested that miR­373 suppresses liver cancer progression and may serve as a promising prognosis prediction biomarker.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , MicroRNAs/genética , Proteínas rab de Ligação ao GTP/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Feminino , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia
15.
Gut ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31383772

RESUMO

OBJECTIVE: Although a subset of genetic loci have been associated with gastric cancer (GC) risk, the underlying mechanisms are largely unknown. We aimed to identify new susceptibility genes and elucidate their mechanisms in GC development. DESIGN: We conducted a meta-analysis of four genome-wide association studies (GWASs) encompassing 3771 cases and 5426 controls. After targeted sequencing and functional annotation, we performed in vitro and in vivo experiments to confirm the functions of genetic variants and candidate genes. Moreover, we selected 33 promising variants for two-stage replication in 7035 cases and 8323 controls from other five studies. RESULTS: The meta-analysis of GWASs identified three loci at 1q22, 5p13.1 and 10q23.33 associated with GC risk at p<5×10- 8 and replicated seven known loci at p<0.05. At 5p13.1, the risk rs59133000[C] allele enhanced the binding affinity of NF-κB1 (nuclear factor kappa B subunit 1) to the promoter of PRKAA1, resulting in a reduced promoter activity and lower expression. The knockout of PRKAA1 promoted both GC cell proliferation and xenograft tumour growth in nude mice. At 10q23.33, the rs3781266[C] and rs3740365[T] risk alleles in complete linkage disequilibrium disrupted and created, respectively, the binding motifs of POU2F1 and PAX3, resulting in an increased enhancer activity and expression of NOC3L, while the NOC3L knockdown suppressed GC cell growth. Moreover, two new loci at 3q11.2 (OR=1.21, p=4.56×10- 9) and 4q28.1 (OR=1.14, p=3.33×10- 11) were associated with GC risk. CONCLUSION: We identified 12 loci to be associated with GC risk in Chinese populations and deciphered the mechanisms of PRKAA1 at 5p13.1 and NOC3L at 10q23.33 in gastric tumourigenesis.

16.
J Oral Maxillofac Surg ; 77(12): 2467-2474, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31445036

RESUMO

PURPOSE: This clinical study aimed to evaluate the long-term efficacy of reconstruction of the gingival interdental papilla via injection of hyaluronic acid gel. MATERIALS AND METHODS: Eight female participants with Class I or II gingival papilla loss in anterior sites were included in this study. The gingival biotype was evaluated previously. Hyaluronic acid gel was injected into the base of the deficient papilla, which was repeated twice at 3 and 6 weeks after the initial injection. The height of the gingival papilla and the area of papilla loss were examined on clinical photographs before treatment and 3, 6, and 12 months after treatment. The data were tested for a normal distribution and analyzed by the Wilcoxon signed rank test. P < .05 was considered significant. RESULTS: The height of the gingival papilla increased 0.311, 0.45, and 0.4 mm from baseline at 3, 6, and 12 months, respectively, after treatment (P < .05), whereas the area of the black triangle was reduced by 0.31, 0.41, and 0.36 mm2 at the same time points (P < .05). In addition, patients with a thick gingival biotype showed a better effect of treatment on the increase in the height of the gingival papilla and decrease in the area of the black triangle. CONCLUSIONS: Our study verified a remarkable effect of hyaluronic acid gel injection in restoring the deficient gingival papilla of the natural teeth, especially in patients with a thick gingival biotype.

17.
Mol Med Rep ; 20(2): 1994-2001, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31257521

RESUMO

In recent decades, an increasing number of studies have demonstrated that numerous microRNAs (miRNAs) are dysregulated in hepatocellular carcinoma (HCC); these aberrantly expressed miRNAs are contributing regulators of HCC formation and progression. Thus, revealing the biological roles of miRNAs in HCC may provide novel information on the identification of effective therapeutic targets and valuable diagnosis methods. Herein, reverse transcription­quantitative PCR was performed to determine the expression profile of miRNA­584 (miR­584) in HCC tissues and cell lines. Cell Counting Kit­8 and cell invasion assays were utilized to evaluate the influence of mIR­584 overexpression on HCC cell proliferation and invasion, respectively. The present study demonstrated that miR­584 expression was reduced in HCC tissues and cell lines compared with normal controls. Clinical analysis indicated that decreased miR­584 expression was significantly associated with tumor size, TNM stage and lymph node metastasis of patients with HCC. Additionally, resumption of miR­584 expression inhibited proliferation and invasion of HCC cells. Mechanistically, it was demonstrated that miR­584 can directly interact with the 3'­untranslated regions of brain­derived neurotrophic factor (BDNF) mRNA, and reduce its mRNA and protein levels in HCC cells. Furthermore, BDNF was upregulated in HCC tissues, and its level was inversely correlated with miR­584 expression. Notably, restored BDNF expression antagonized the inhibitory effects of miR­584 overexpression on HCC cells. In conclusion, miR­584 may serve tumor­suppressive roles in HCC by directly targeting BDNF, thus suggesting that miR­584 may serve as a potential candidate for treatment of patients with this disease.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Apoptose/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética
18.
Future Med Chem ; 11(12): 1427-1442, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31304828

RESUMO

Aim: Fusidic acid (FA) is an effective antibiotic against Staphylococcus aureus, but it is metabolically unstable. Methods & results: 14 derivatives were designed and synthesized by blocking the metabolic sites of FA (21-COOH and 3-OH) to maintain antibacterial activity and prolong the half-life. Six derivatives showed good antibacterial activity, and the pharmacokinetic experiments confirmed that two derivatives modified in 21-COOH released FA in vivo and showed longer half-lives than FA. Docking analysis and structure-activity relationships indicated that the 3-glycine derivatives with more hydrogen-bonding acceptor sites and positively charged surface areas were more likely to have good antibacterial activity. Conclusion: The results suggest that introducing groups that block the metabolic sites of FA could maintain antibacterial activity and prolong the half-lives.

19.
Oxid Med Cell Longev ; 2019: 1958941, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31182988

RESUMO

Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) are a promising new therapeutic option for myocardial infarction (MI). The tissue matrix metalloproteinase inhibitor 2, also known as TIMP2, is a member of the tissue inhibitor family of metalloproteinases. Since TIMP2-mediated inhibition of matrix metalloproteinases (MMPs) is a key determinant of post-MI remodeling, we analyzed the therapeutic effects of exosomes derived from TIMP2-overexpressing hucMSCs (huc-exoTIMP2) on the MI rat model. The huc-exoTIMP2 significantly improved in vivo cardiac function as measured by echocardiography and promoted angiogenesis in MI injury. It also restricted extracellular matrix (ECM) remodeling, as indicated by the reduced collagen deposition. In addition, huc-exoTIMP2 administration increased the in situ expression of the antiapoptotic Bcl-2 and decreased that of the proapoptotic Bax and pro-caspase-9 in the infracted myocardium. Meanwhile, huc-exoTIMP2 upregulated superoxide dismutase (SOD) as well as glutathione (GSH) and decreased the malondialdehyde (MDA) level in MI models. In vitro huc-exoTIMP2 pretreatment could inhibit H2O2-mediated H9C2-cardiomyocyte apoptosis and promote human umbilical vein endothelial cell (HUVEC) proliferation, migration, and tube formation, as well as decrease TGFß-induced MMP2, MMP9, and α-SMA secretion by cardiac fibroblasts (CFs). Besides that, huc-exoTIMP2 pretreatment also increased the expression of Akt phosphorylation in the infarcted myocardium, which may relate to a high level of secreted frizzled-related protein 2 (Sfrp2) in huc-exoTIMP2, indicating a mechanistic basis of its action. Importantly, Sfrp2 knockdown in huc-exoTIMP2 abrogated the protective effects. Taken together, huc-exoTIMP2 improved cardiac function by alleviating MI-induced oxidative stress and ECM remodeling, partly via the Akt/Sfrp2 pathway.


Assuntos
Exossomos/metabolismo , Proteínas de Membrana/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Infarto do Miocárdio/terapia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Cordão Umbilical/citologia , Animais , Apoptose/fisiologia , Proliferação de Células/fisiologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Malondialdeído/metabolismo , Estresse Oxidativo/fisiologia , Ratos
20.
Chin J Integr Med ; 25(8): 565-573, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31069693

RESUMO

In order to solve the problem of long-term (>9 months) efficacy in the treatment of Alzheimer's disease (AD) by conventional therapy (CT), a staged and multiply-targeted sequential therapy based on the evolvement of patterns (STEP) was developed. Its main innovations include: (1) the time order of evolution of patterns defined by Chinese medicine (CM) in AD was found, that is, "the orderly pattern evolution starting from Shen (Kidney) deficiency, progressing to phlegm, stasis and fire, and worsening to severe toxin as well as functional collapse"; (2) the cascade hypothesis of Shen deficiency in AD and its sequential therapy based on Shen-reinforcing was proposed, that is, "reinforcing Shen in the early stage and throughout the whole process, resolving phlegm, activating blood and purging fire in the middle stage, detoxifying and replenishing vitality to stop the collapse in the advanced stage", and through meta-analysis, clinical drug use was optimized, thus the leap from "inferential selection" to "evidence-based selection" was realized; (3) the STEP regimen combined with CT maintained cognitive and behavioral stability in AD patients for at least 12 months, with cognitive enhancement and behavioral synergy after 9 months, and cognitive benefit was superior to CT at 9, 12, 15, 18, 21, and 24 months, respectively. The 2-year cognitive improvement rate was increased by 25.64% (P=0.020) and the cognitive deterioration rate was decreased by 48.71% (P=0.000). Among them, the cognitive and functional benefits of Shen-reinforcing therapy for very early AD (350 cases) for 1 year were better than the placebo (P<0.001), and the dementia conversion rate was reduced by 8.85% (P=0.002). The behavioral symptomatic relief of patients with vascular dementia received fire-purging therapy (540 cases) was superior to those received CT (P=0.016). These data suggested that the STEP regimen has synergistic effects on CTs at least in terms of cognitive benefit, and the earlier the use, the greater the benefit will have. Therefore, the STEP regimen should be considered as one of the clinical options, particularly for the dearth of effective pharmaceutical or immunological interventions that are currently available for AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Modelos Biológicos , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Baseada em Evidências , Humanos , Medicina Tradicional Chinesa
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