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1.
World Neurosurg ; 133: e225-e232, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31493599

RESUMO

OBJECTIVE: To identify and reveal the sensitivity and efficiency of dynamic somatosensory evoked potentials (DSSEPs) in the diagnosis of cervical spondylotic myelopathy (CSM). METHODS: This retrospective study included 31 CSM and 15 control patients. All patients received SSEP examination with stimulation of median and ulnar nerves at neutral, flexed, and extended cervical positions; latency and amplitude were recorded at the C2 and C5 spinous processes and in the scalp over the primary sensory area (C3'/4'). The percentage changes in latency and amplitude with dynamic motion were examined for each lead and compared between groups; the diagnostic cutoff values were determined using receiver operating characteristic curve analysis. RESULTS: All the patients with CSM received surgeries and were followed up for 1 year. Amplitude parameters varied with a dynamic position in both groups; all recorded dynamic SSEP indices except right median stimulus recorded at C5 spinous process, right ulnar stimulus recorded at scalp point C3, and right ulnar stimulus recorded at C2 spinous process were significantly different between groups (P < 0.05), but latency was not (P > 0.05). At the neutral position, the amplitude of left media stimulus recorded at C2 spinous process (LMC2) was associated with CSM, but with low diagnostic accuracy (area under the curve = 0.199). At a dynamic position, the percentage change in amplitude of LMC2 and of left ulnar stimulus recorded at C2 spinous process (LUC2) were determined to be diagnostic of CSM (P < 0.05), with areas under the curve of 0.891 and 0.912, respectively. Both records had high sensitivity and specificity in the diagnosis of CSM; the diagnostic cutoff values of LMC2 and LUC2 were calculated as 10.2% and 19.25%, respectively. CONCLUSIONS: The percentage change in amplitude was obvious during cervical dynamic motion, with records from LMC2 and LUC2 being predictive of CSM diagnosis; dynamic SSEPs provided a simple, accurate, and noninvasive supplementary test for the diagnosis of complicated CSM.

2.
Cancer Lett ; 469: 22-34, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31634528

RESUMO

Hepatocellular carcinoma (HCC) has emerged as one of the most common malignancies worldwide. It is associated with a high mortality rate, as evident from its increasing incidence and extremely poor prognosis. The deubiquitinating enzyme 26S proteasome non-ATPase regulatory subunit 14 (PSMD14) has been reported to act as an oncogene in several human cancers. The present study aimed to reveal the functional significance of PSMD14 in HCC progression and the underlying mechanisms. We found that PSMD14 was significantly upregulated in HCC tissues. Overexpression of PSMD14 correlated with vascular invasion, tumor number, tumor recurrence, and poor tumor-free and overall survival of patients with HCC. Knockdown and overexpression experiments demonstrated that PSMD14 promoted proliferation, migration, and invasion in HCC cells in vitro, and facilitated tumor growth and metastasis in vivo. Mechanistically, we identified PSMD14 as a novel post-translational regulator of GRB2. PSMD14 inhibits degradation of GRB2 via deubiquitinating this oncoprotein in HCC cells. Furthermore, pharmacological inhibition of PSMD14 with O-phenanthroline (OPA) suppressed the malignant behavior of HCC cells in vitro and in vivo. In conclusion, our findings suggest that PSMD14 could serve as a novel promising therapeutic candidate for HCC.

3.
Free Radic Biol Med ; 147: 159-166, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31874250

RESUMO

OBJECTIVE: To investigate the role of geranylgeranyl diphosphate synthase 1 (GGPPS1) in ventilator-induced lung injury along with the underlying mechanism. METHODS: A murine VILI model was induced by high-tidal volume ventilation in both wild-type and GGPPS1 knockout mice. GGPPS1 expression was detected in the bronchoalveolar lavage fluid (BALF) supernatants of acute respiratory distress syndrome (ARDS) patients and healthy volunteers, as well as in lung tissues and BALF supernatants of the VILI mice using enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription polymerase chain reaction (qRT-PCR), western bolt and immunohistochemical (IHC). The wet/dry ratio, total BALF proteins, and lung injury score were analyzed. The percentage of neutrophils was detected by flow cytometry and IHC. Inflammatory cytokine levels were measured by ELISA and qRT-PCR. The related expression of Toll-like receptor (TLR)2/4 and its downstream proteins was evaluated by western blot. RESULTS: GGPPS1 in BALF supernatants was upregulated in ARDS patients and the VILI mice. Depletion of GGPPS1 significantly alleviated the severity of ventilator induced lung injury in mice. Total cell count, neutrophils and inflammatory cytokines (interleukin [IL]-6, IL-1ß, IL-18 and tumor necrosis factor-α) levels in BALF were reduced after GGPPS1 depletion. Moreover, addition of exogenous GGPP in GGPPS-deficient mice significantly exacerbated the severity of ventilator induced lung injury as compared to the PBS treated controls. Mechanistically, the expression of TLR2/4, as well as downstream proteins including activator protein-1 (AP-1) was suppressed in lung tissues of GGPPS1-deficient mice. CONCLUSION: GGPPS1 promoted the pathogenesis of VILI by modulating the TLR2/4-AP-1 signaling pathway, and GGPPS1 knockout significantly alleviated the lung injury and inflammation in the VILI mice.

4.
Oncogene ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666682

RESUMO

WNT5B glycoprotein belongs to the Wnt protein family. Limited investigations revealed a possible role of WNT5B in malignancies, such as triple-negative breast cancer and oral squamous cell carcinoma. However, whether WNT5B contributes to the progression of lung adenocarcinoma (LAD) remains unclear. Here, we initially determine that WNT5B is highly expressed in LAD and is positively correlated with lymph node metastasis and TNM stage. Consistently, clinical analysis reveals WNT5B as an independent prognostic biomarker in LAD. Silencing WNT5B suppresses the proliferation of LAD both in vitro and in vivo by interfering G1/S cell-cycle progression and modulating amino acid metabolism, revealing its remarkable oncogenic role in LAD. Of note, we also identified miR-5587-3p as a negative upstream regulator of WNT5B in LAD, which may help develop therapies targeting LAD patients with high WNT5B expression. Taken together, our results revealed an oncogenic role of WNT5B in LAD, which could be a prognostic biomarker and promising therapeutic target for LAD patients.

5.
Biochem Genet ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31696339

RESUMO

Mitochondrial DNA (mtDNA) has been widely employed as one tool for the studies of human migration and phylogenetic evolution owing to the characteristics of its lack of recombination and matrilineal inheritance. In this study, we analyze genetic distributions of 60 mtDNA markers in 126 unrelated individuals of Southern Shaanxi Han population and classify their haplogroups. Genetic distribution comparisons between Southern Shaanxi Han and other populations from different continents are conducted based on the same mtDNA markers. The majority of 60 mtDNA markers are polymorphic in Southern Shaanxi Han population. The most common haplogroups observed in Southern Shaanxi Han population are B5, followed by D5, A, D4e, and N9a1'3. Obtained matching probability for these 60 mtDNA markers indicates that the panel could be used as a valuable tool in forensic caseworks. Results of genetic distances (Fst) and multidimensional scaling analysis show that Southern Shaanxi Han population has relatively close genetic relationships with other Han populations in different regions. In conclusion, the panel comprising 60 mtDNA markers could be utilized for forensic applications in Southern Shaanxi Han population.

6.
Medicine (Baltimore) ; 98(42): e17341, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626091

RESUMO

RATIONALE: Schwannomas grow slowly, originating from the Schwann cells of the nerve sheath. Schwannomas of cranial origin have the highest incidence, followed by intraspinal schwannomas. However, paravertebral schwannoma is rare, and to our knowledge, giant paravertebral schwannomas near the lumbar nerve roots with bone destruction are extremely rare. PATIENT CONCERNS: A 47-year-old Chinese woman complained of lower back soreness and a sensation of a bulging lumbar disc with no obvious cause for the past 3 years. DIAGNOSIS: Lumbar magnetic resonance imaging showed a large mass with uneven density, 17 × 12 × 15 cm in size, located to the right of the 4th lumbar with obvious bony destruction. Histopathology and immunohistochemistry confirmed that this mass was a benign schwannoma. INTERVENTIONS: Complete resection of the tumor (measuring about 17 × 12 × 15 cm in size) and vertebral reconstruction using internal fixation were performed. OUTCOMES: The patient was discharged without complications after surgery. The 3-year follow-up revealed that the patient recovered well with no evidence of recurrence. LESSONS: Here, we emphasize the importance of careful radiological examination and reflect on the difficulty of tumor resection. Furthermore, understanding the treatment and diagnosis of lumbar paravertebral schwannoma is critical for plastic surgeons and radiologists when encountering similar cases.


Assuntos
Vértebras Lombares/patologia , Neurilemoma/patologia , Neoplasias da Coluna Vertebral/patologia , Raízes Nervosas Espinhais/patologia , Feminino , Humanos , Dor Lombar/etiologia , Vértebras Lombares/virologia , Região Lombossacral/diagnóstico por imagem , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Neurilemoma/diagnóstico por imagem , Neurilemoma/cirurgia , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/cirurgia , Raízes Nervosas Espinhais/diagnóstico por imagem , Raízes Nervosas Espinhais/cirurgia , Resultado do Tratamento
7.
Transl Lung Cancer Res ; 8(4): 413-428, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31555516

RESUMO

Background: We conducted a meta-analysis to evaluate the efficacy of anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) monotherapy or immunotherapy combined with chemotherapy and further estimated the value of PD-L1 expression in predicting the response from anti-PD-1/PD-L1 treatments as monotherapy or in combination with chemotherapy. Methods: Clinical trial data were searched from electronic databases, which evaluated PD-1/PD-L1 inhibitors in non-small cell lung cancer (NSCLC) and correlated with PD-L1 expression levels. Results: Fifteen randomized-controlled trials involving 10,074 patients were identified. Comparing anti-PD-1/PD-L1 monotherapy to chemotherapy, the pooled HR for overall survival (OS) was 0.77 (95% CI: 0.69-0.85, P<0.00001). Subgroup analyses revealed that patients had longer OS at ≥1%, ≥5%, ≥10% and ≥50% PD-L1 expression levels. Patients with higher PD-L1 expression may get increased benefit from PD-1/PD-L1 inhibitors. Moreover, patients with PD-L1 ≥50% had an objective response rate (ORR) improvement from anti-PD-1/PD-L1 therapy (RR =1.87, 95% CI: 1.27-2.75, P=0.001), but no ORR benefits were observed in patients with PD-L1 expression <1% (RR =0.82, 95% CI: 0.56-1.22, P=0.33) or 1-49% (RR =0.80, 95% CI: 0.64-0.98, P=0.03). OS was significantly better in patients receiving second-or-third line treatments (P<0.00001) with PD-L1 ≥1%. The efficacy of PD-1 inhibitors was similar to that of PD-L1 inhibitors, with no significant difference (P=0.63, I2=0%). Furthermore, immunotherapy combined with chemotherapy had better OS (HR =0.64, 95% CI: 0.48-0.84, P=0.001) than chemotherapy alone. Subgroup analyses showed that patients benefited from the combined chemo-IO treatment in the first-line setting regardless of PD-L1 expression level. Conclusions: PD-L1 expression may be a valuable predictor of the efficacy of anti-PD-1/PD-L1 monotherapy in certain NSCLC patients. However, the combination of chemotherapy plus immunotherapy significantly improved survival regardless of the PD-L1 expression level in the first-line treatment of NSCLC.

8.
Transl Lung Cancer Res ; 8(4): 429-449, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31555517

RESUMO

Background: We conducted a meta-analysis to systematically evaluate the relationship between programmed death-ligand 1 (PD-L1) expression and survival in patients with lung cancer. Methods: The electronic databases PubMed, Embase, Cochrane, and Web of Science were searched up to January 2nd, 2018, for articles relating to PD-L1 expression detected by immunohistochemistry (IHC) and lung cancer patient prognosis. Results: Fifty studies including 11,383 patients published between 2011 and 2017 were enrolled in this meta-analysis. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) suggested that PD-L1 IHC expression was related to poor overall survival (OS) (HR =1.45, 95% CI: 1.24-1.68). In subgroup analysis categorized according to sample type, cut-off value, ethnicity and TNM stage, the pooled results demonstrated inferior survival in the PD-L1 positive group when the PD-L1 expression was detected by resection specimens (P=0.000), 5% was taken as the cutoff value (P=0.000), the patients were in early stage (I-III) (P=0.000), and the geographic setting of the study was in Asia (P=0.000). Besides, patients with high PD-L1 expression had shorter OS in NSCLC (P=0.000), ADC (P=0.000), SCC (P=0.353) and LELC (P=0.810), while no significant difference was observed in SCLC (P=0.000). The pooled odds ratios (ORs) suggested that PD-L1 expression was associated with male (P<0.001), smoker (P<0.001), poor tumor differentiation (P=0.014), large tumor size (P=0.132), positive lymph nodal metastasis (P=0.002), EGFR wild-type status (P<0.001) and KRAS mutations (P=0.393). However, age (P=0.15) and ALK rearrangements (P=0.567) had no bearing on PD-L1 expression. Conclusions: PD-L1 expression that is associated with several clinicopathological feactures may serve as a poor prognostic biomarker for patients with lung cancer.

9.
Transl Lung Cancer Res ; 8(3): 214-226, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31367535

RESUMO

Background: Neutrophil-to-lymphocyte ratio (NLR) is related to prognosis in non-small cell lung cancer (NSCLC). However, no consensus on the relationship of pretreatment NLR and survival outcomes of systemic therapy in NSCLC exists. This meta-analysis investigated the prognostic role of pretreatment NLR during systemic therapy for NSCLC, including chemotherapy, immunotherapy and targeted therapy. Methods: PubMed, Web of Science and Cochrane Library databases were systematically searched up to April 09, 2019. Hazard ratios (HRs) with their 95% confidence intervals (CIs) were pooled to investigate the association of pretreatment NLR with progression-free survival (PFS) and overall survival (OS). Results: In total, 27 articles with 4,298 participants were selected. The pooled results showed that elevated pretreatment NLR was associated with inferior PFS (HR, 1.45, 95% CI, 1.28-1.66) and OS (HR, 1.63, 95% CI, 1.43-1.84) during systemic therapy. Subgroup analyses according to the treatment strategy suggested that higher pretreatment NLR was significantly associated with shorter survival in all therapies, including chemotherapy (PFS HR, 1.74, 95% CI, 1.39-2.17; OS HR, 1.73, 95% CI, 1.26-2.36), immunotherapy (PFS HR, 1.53, 95% CI, 1.27-1.84; OS HR, 2.50, 95% CI, 1.60-3.89) and targeted therapy (PFS HR, 1.53, 95% CI, 1.04-2.25; OS HR, 1.92, 95% CI, 1.14-3.24). Conclusions: Pretreatment NLR is a promising prognostic indicator for NSCLC patients receiving systemic therapy, including chemotherapy, immunotherapy and targeted therapy.

10.
Transl Lung Cancer Res ; 8(3): 302-316, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31367543

RESUMO

Sensitizing mutations in epidermal growth factor receptor (EGFR) are associated with positive responses to anti-EGFR-targeted therapy, leading to a new era of treatment for non-small cell lung cancer (NSCLC). Exon 19 deletions and exon 21 L858R substitutions are the most common mutations, accounting for approximately 90% mutations in NSCLC; these are termed classic mutations and result in high sensitivity to tyrosine kinase inhibitors (TKIs). Other EGFR mutations are termed uncommon EGFR mutations, of which G719X, S768I, L861Q, exon 20 insertions, and complex mutations are the most frequent. G719X, S768I, and L861Q are point mutations and those that exist with complex mutations are sensitive to first-generation TKIs. A prospective analysis demonstrated that afatinib, a second-generation TKI, led to a better prognosis in some patients with NSCLC compared to first-generation TKIs. Chemotherapy used to be the traditional choice for patients carrying exon 20 insertions; however, with the development of novel targeted drugs, the role of chemotherapy is changing. Tremendous progress has also been made in clinical trials on immunotherapy treatment of uncommon EGFR mutations. The treatment for patients with NSCLC harboring uncommon EGFR mutations remains a subject of debate and the sensitivity of uncommon EGFR mutations to TKIs is still unclear. Here, we summarized recent data in the literature and provide an overview of the clinical characteristics, incidence, and outcomes of patients harboring G719X, S768I, L861Q, exon 20 insertions, and complex mutations who were treated with TKIs, chemotherapy, or immunotherapy.

11.
Biomed Res Int ; 2019: 3129748, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31346515

RESUMO

About half of NSCLC patients with EGFR mutation had secondary mutation T790M after treatment with a first-generation tyrosine kinase inhibitor (TKI), Gefitinib. The third-generation of EGFR-TKI Osimertinib is suitable for patients with EGFR mutation and T790M mutation. However, drug screening for NSCLC patients after the emergence of acquired resistance has become a difficult problem for clinicians. In this study, we established drug-resistant cell lines of Gefitinib and Osimertinib to evaluate cell proliferation in vitro. And we investigated the inhibitory effect of different drug concentration gradients on cancer cells. Zebrafish with high homology to human genes were selected as xenotransplantation models to compare the effects of different concentrations of Osimertinib on the proliferation and angiogenesis of zebrafish tumors after transplantation of different lung cancer cell lines. It was confirmed that Osimertinib could inhibit the proliferation of tumor cells with EGFR mutation and T790M resistance mutation in zebrafish, which was consistent with the clinical research conclusion.


Assuntos
Acrilamidas/farmacologia , Compostos de Anilina/farmacologia , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Gefitinibe/efeitos adversos , Gefitinibe/farmacologia , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Inibidores de Proteínas Quinases/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-Zebra/genética
12.
Int Immunopharmacol ; 74: 105713, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31276977

RESUMO

GSDMD is a recently discovered pyroptosis executioner in monocytes whose N-terminal domain can insert into the inner leaflet of cell membranes and form extensive pores. However, the function of GSDMD in other biological systems remains unclear. In this study, we showed that the expression of GSDMD was consistently correlated with CD8+ T cell markers in The Cancer Genome Atlas (TCGA) cohorts. GSDMD cleavage increased in OT-1 cytotoxic T lymphocytes (CTLs) and human activated CD8+ T cells. Colocalization of GSDMD with granzyme B was observed in the proximity of immune synapses, and GSDMD deficiency reduced the cytolytic capacity of CD8+ T cells. Overall, our study highlights a function, to our knowledge previously unknown, for GSDMD in CTLs and demonstrated that GSDMD is required for an optimal CTL response to cancer cells.

13.
Int J Anal Chem ; 2019: 8963191, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31057622

RESUMO

A single-factor gradual optimization method was developed in this experiment in order to improve the headspace solid-phase microextraction (HS-SPME) effect of volatile compounds in pepper chicken soup. The different extraction conditions included fibers with different coating materials, sample volume, extraction temperature, and extraction time. The total peak areas and the numbers of valid peaks were compared and analyzed as the indicators of condition optimization. Gas chromatography-mass spectrometry (GC-MS) results showed that the four factors all have significant impact on the extraction effect of volatiles in pepper chicken soup. Using the principal component analysis (PCA), the optimal conditions of HS-SPME were inferred below: an extraction fiber of 50/30µm DVB/CAR/PDMS, a sample volume of 7 g, an extraction temperature of 65°C, and an extraction time of 30 min. Compared to the original extraction conditions, the optimized conditions were especially advantageous for the comprehensive analysis of volatiles, which could be potentially used in further study of soup.

14.
Biochem Biophys Res Commun ; 514(3): 691-698, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31078267

RESUMO

Both oxidative stress and inflammation contribute to the development of insulin resistance (IR). Curcumin (Cur) not only has an anti-inflammatory effect but also has an antioxidative stress effect via the activation of NF-E2-related factor 2 (Nrf2). Since there is close cross-communication between inflammation and oxidative stress, we examined whether Cur could modulate Nrf2 function via its anti-inflammatory ability and investigated its underlying mechanism. In this study, we show that Cur inhibits inflammatory signaling and Kelch-like ECH-associated protein 1 (Keap1) expression, which is accompanied by the activation of the Nrf2 system. We further identified that the proinflammatory cytokine tumor necrosis factor alpha (TNFα) could stimulate Keap1 synthesis and increase Nrf2 polyubiquitination, but these effects could be significantly inhibited by Cur treatment. This study demonstrates that Cur-induced Nrf2 activation occurs through the inhibition of inflammatory signaling-mediated upregulation of Keap1, contributing to its beneficial effects on redox homeostasis and insulin sensitivity.

15.
Cancer Manag Res ; 11: 2485-2497, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31118766

RESUMO

Background: Hepatocellular carcinoma (HCC) is one of the most frequent cancers and the third leading cause of cancer-related deaths. It has been reported that lysosomal associated transmembrane protein LAPTM4B expression is significantly upregulated in human cancers and closely associated with tumor initiation and progression. Purpose: We aimed to reveal the relevance of LAPTM4B and the pathogenesis of HCC. Methods: Cell viability assessment, colony formation assay, in vivo xenograrft model, microarray, real-time PCR, immunofluorescence and western blot analysis were applied. Results: Our results demonstrated that LAPTM4B promoted HCC cell proliferation in vitro and tumorigenesis in vivo. Additionally, upon starvation conditions, LAPTM4B facilitated cell survival, inhibited apoptosis and induced autophagic flux. Expression profiling coupled with gene ontology (GO) analysis revealed that 159 gene downregulated by LAPTM4B silencing was significantly enriched in response to nutrient and some metabolic processes. Moreover, LAPTM4B activated ATG3 transcription to modulate HCC cell apoptosis and autophagy. Conclusion: Our findings demonstrate that LAPTM4B acts as an oncogene that promotes HCC tumorigenesis and autophagy, and indicate that LAPTM4B may be used as a novel therapeutic target for HCC treatment.

16.
J Clin Psychopharmacol ; 39(3): 243-248, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30925499

RESUMO

PURPOSE: This study aimed to explore the effect of extended-release paliperidone (paliperidone ER) and olanzapine on heart rate variability (HRV) in patients with schizophrenia. METHODS: A total of 106 patients with schizophrenia diagnosed by the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) were randomly divided into the paliperidone ER group or the olanzapine group for an 8-week clinical trial, with 53 patients in each group. The time domain and frequency domain analyses including the SD of all the R-R intervals in 24 hours (SDNN), the SD of the mean value of all the normal R-R intervals in every 5-minute interval within 24 hours (SDANN index), the mean value of the SD of all the normal R-R intervals in every 5-minute interval within 24 hours (SDNN index), the root mean square of successive R-R differences, the percentage of adjacent R-R intervals that differ by more than 50 milliseconds, high-frequency power (HF), low-frequency power (LF), and LF/HF were adopted to assess the HRV of patients at baseline and after treatment for 8 weeks in each group. The Positive and Negative Symptom Scale was used to evaluate the clinical efficacy. The incidence rates of adverse reactions were also calculated. RESULTS: In total, 48 patients in the paliperidone ER group and 45 patients in the olanzapine group completed the entire 8-week treatment. The SDNN, SDNN index, and SDANN index in the olanzapine group were significantly lower than those in the paliperidone ER group (P < 0.05) after treatment for 8 weeks, whereas their mean LF level was higher than that in the paliperidone ER group (P < 0.05) after completion of treatment. Patients in the olanzapine group showed a significant decrease in the SDNN, SDANN index, and SDNN index as well as a statistical increase in the LF and LF/HF in comparison with the pretreatment values (P < 0.05), whereas patients in the paliperidone ER group showed a decrease in the SDANN index and a statistical increase in the LF in comparison with the pretreatment values (P < 0.05). CONCLUSION: The HRV of patients with schizophrenia changes when they are administered with paliperidone ER or olanzapine, and more attention should be paid to their cardiac autonomic function when using these 2 antipsychotics.


Assuntos
Antipsicóticos/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Olanzapina/administração & dosagem , Palmitato de Paliperidona/administração & dosagem , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/efeitos adversos , Preparações de Ação Retardada , Feminino , Humanos , Masculino , Olanzapina/efeitos adversos , Palmitato de Paliperidona/efeitos adversos , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Fatores de Tempo
17.
Med Mycol ; 57(8): 954-961, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30657948

RESUMO

Sporotrichosis is a subcutaneous mycosis caused by traumatic inoculation of pathogenic Sporothrix species. Until recently, Sporothrix globosa was considered as the unique Chinese species causing this disorder. In the present study, 33 clinical Sporothrix strains isolated from Jiangxi, China, were classified and antifungal susceptibility for each strain was determined. Thirteen S. globosa strains and 20 S. schenckii strains were identified by morphology and by multilocus analysis using rDNA ITS, CAL, and EF1α (i.e., internal transcribed spacer, calmodulin and elongation factor-1α). In vitro antifungal susceptibility testing of yeast phases indicated that itraconazole, terbinafine, and posaconazole were most effective against both species, followed by amphotericin B and voriconazole, while fluconazole, 5-fluorocytosine had low efficacy with high MICs. Co-occurrence of S. schenckii and S. globosa in central China may indicate different routes of transmission in this area.


Assuntos
Antifúngicos/farmacologia , Sporothrix/classificação , Sporothrix/efeitos dos fármacos , Esporotricose/epidemiologia , Esporotricose/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , DNA Espaçador Ribossômico/genética , Feminino , Genótipo , Humanos , Masculino , Testes de Sensibilidade Microbiana , Microscopia , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Fator 1 de Elongação de Peptídeos/genética , Prevalência , Sporothrix/isolamento & purificação , Adulto Jovem
18.
Am J Physiol Lung Cell Mol Physiol ; 316(3): L567-L577, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30652497

RESUMO

Inhibition of the mevalonate pathway using statins has been shown to be beneficial in the treatment of acute lung injury (ALI). Here, we investigated whether partial inhibition of this pathway by targeting geranylgeranyl pyrophosphate synthase large subunit 1 (GGPPS1), a catalase downstream of the mevalonate pathway, was effective at treating lung inflammation in ALI. Lipopolysaccharide (LPS) was intratracheally instilled to induce ALI in lung-specific GGPPS1-knockout and wild-type mice. Expression of GGPPS1 in lung tissues and alveolar epithelial cells was examined. The severity of lung injury and inflammation was determined in lung-specific GGPPS1 knockout and wild-type mice by measuring alveolar exudate, neutrophil infiltration, lung injury, and cell death. Change in global gene expression in response to GGPPS1 depletion was measured using mRNA microarray and verified in vivo and in vitro. We found that GGPPS1 levels increased significantly in lung tissues and alveolar epithelial cells in LPS-induced ALI mice. Compared with wild-type and simvastatin treated mice, the specific deletion of pulmonary GGPPS1 attenuated the severity of lung injury by inhibiting apoptosis of AECs. Furthermore, deletion of GGPPS1 inhibited LPS-induced inflammasome activation, in terms of IL-1ß release and pyroptosis, by downregulating NLRP3 expression. Finally, downregulation of GGPPS1 reduced the membrane expression of Ras-related protein Rab10 and Toll-like receptor 4 (TLR4) and inhibited the phosphonation of IκB. This effect might be attributed to the downregulation of GGPP levels. Our results suggested that inhibition of pulmonary GGPPS1 attenuated LPS-induced ALI predominantly by suppressing the NLRP3 inflammasome through Rab10-mediated TLR4 replenishment.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/efeitos dos fármacos , Pneumonia/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Animais , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Camundongos Transgênicos , Pneumonia/metabolismo
19.
Mycoses ; 62(5): 466-474, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30597639

RESUMO

Trichophyton schoenleinii is an anthropophilic dermatophyte usually causing tinea favosa. Only few studies have provided data on molecular epidemiology and antifungal profiles of this fungus due to its limited prevalence after 1950s. Forty-nine strains from Asia (n = 27), Africa (n = 10), Europe (n = 10) and from unknown regions (n = 2) were analysed with amplified fragment length polymorphism fingerprinting (AFLP) to reveal intraspecific genetic diversity in this dataset. Amplified fragment length polymorphism fingerprinting genotyping revealed five clusters which did not correspond to geographic origins or clinical characteristics. Additionally, in vitro antifungal susceptibility to seven antifungals was provided for all strains. Terbinafine, ketoconazole, miconazole and itraconazole proved to be the most effective drugs, followed by griseofulvin. No correlation between genotypes and differences in antifungal susceptibility was observed. It is concluded that the AFLP groups are lineages within a single species.


Assuntos
Antifúngicos/farmacologia , Variação Genética , Tinha do Couro Cabeludo/epidemiologia , Tinha do Couro Cabeludo/microbiologia , Trichophyton/classificação , Trichophyton/efeitos dos fármacos , África , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Ásia , Europa (Continente) , Genótipo , Técnicas de Genotipagem , Humanos , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Técnicas de Tipagem Micológica , Prevalência , Trichophyton/genética , Trichophyton/isolamento & purificação
20.
Pak J Pharm Sci ; 32(6): 2625-2632, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31969295

RESUMO

Ferula lehmannii Boiss (FLB) is a perennial plant that belongs to the family Apiaceae, which is a traditional remedy used to treat gastric ulcers in Xinjiang. The main purpose of the research is to investigate the possible antiulcer effect of three different extracts, water decoction (WD), fresh liquid (FL), and chloroform extract (CE), using a model of acetic acid-induced gastric ulcer. 56 rats were divided into seven groups (n=8) and treated ranitidine and extracts of FLB. After 12 days of treatment, the ulcer index and biochemical parameters were evaluated. In all tested groups, the results indicated that the chloroform extract and water decoction highly significantly decreased the mucosal damage index as compared to the model group, restoration of glutathione per oxidase (GSH-PX) levels and super oxide dismutase (SOD) activity, and reduction of malondialdehyde (MDA) levels. The ulcer inhibition rate of water decoction group, fresh liquid and chloroform extract group reached 25.30%, 4.96% and 30.87%, respectively. The macroscopic observations were supported by histological findings. 44, 31, 32 compounds were identified through GC-MS analysis of different extracts. In conclusion, FLB exhibits potential anti-ulcer activity attributed to its high content terpenoid, phytosterin and fatty acid, the underlying antiulcer mechanism might be relevant to the reduction in inflammation and oxidative stress.

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