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1.
ANZ J Surg ; 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32115876

RESUMO

BACKGROUND: To investigate the clinical efficacy and mechanism of laparoscopic sleeve gastrectomy (LSG) in improving renal function in obese patients. METHODS: We retrospectively reviewed the anthropometric indices (waist circumference, hip circumference and body mass index (BMI)), renal function indices (serum creatinine, urea and urinary albumin:creatinine ratio (UACR)), serum inflammatory indices (C-reactive protein, interleukin-6 and tumour necrosis factor-α) and an adipose factor (leptin) in 50 patients with obesity (BMI ≥32.5 kg/m2 ) who underwent LSG in our hospital from January 2018 to January 2019. RESULTS: Patients constituted 23 men and 27 women, with an average age of 32.5 ± 8.7 years and BMI of 43.99 ± 8.29 kg/m2 . Body weight and BMI 1 month post-operatively were significantly lower than preoperatively (P < 0.05), and the renal function indices serum creatinine, urea and UACR, improved significantly 3 months post-operatively (P < 0.05). C-reactive protein, interleukin-6 and tumour necrosis factor-α levels improved significantly 3 months post-operatively (P < 0.05), while leptin levels decreased significantly 1 month post-operatively (P < 0.05). Six months post-operatively, the remission rates for type 2 diabetes mellitus, sleep apnoea syndrome and hypertension were 83.8%, 92.9% and 88.6%, respectively. CONCLUSIONS: LSG led to body weight loss and significantly improved serum creatinine, urea and UACR values in patients with obesity, which may be related to changes in adipocytokines and inflammatory factors, post-operatively. LSG is expected to become a new treatment to prevent or treat renal insufficiency caused by obesity.

2.
BMC Mol Cell Biol ; 21(1): 4, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32013860

RESUMO

BACKGROUND: PM2.5 is associated closely with an increased risk of membranous nephropathy (MN), however, whether PM2.5 could induce podocytes injury, the underlying pathology for MN, has not be thoroughly studied. Triptolide, an active component in Tripterygium wilfordii Hook F, is frequently used to treat MN in China, but its effects on PM2.5-induced podocytes injury is still largely unknown. Therefore, we evaluated the effects of PM2.5 on podocytes, and explored whether triptolide could improve PM2.5-induced podocytes injury and the possible underlying mechanisms. RESULTS: Podocytes were incubated with PM2.5 after being pre-treated with triptolide, viability, apoptosis rate and migratory capacity of podocytes were determined by CCK-8 assay, flow cytometry and Transwell assay, respectively. Additionally, the levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD) in podocytes, the cytoskeleton of podocytes, the protein expressions of nephrin, podocin, Bcl-2, Bax, nuclear factor kappa-B/p65 (NF-κB/p65) and phospho-inhibitor of NF-κB (p-IκBα) were measured. Our data showed that PM2.5 treatment significantly increased the disorganization of F-actin stress fibers, the damaged structural integrity of nucleus, the deranged and dissociated cytoskeleton in podocytes, increased the podocytes apoptosis rate, the levels of MDA and LDH, markedly up-regulated the protein expression of Bax, NF-κB/p65 and p-IκBα, down-regulated the protein expression of nephrin, podocin and Bcl-2, and significantly decreased the level of SOD, the migration rate and the viability of podocytes, compared with those of the untreated podocytes. These effects of PM2.5 on podocytes, however, were reversed by triptolide administration. CONCLUSION: These results suggest that triptolide could prevent against PM2.5-induced podocytes injury via suppressing NF-κB signaling pathway.

3.
BMC Musculoskelet Disord ; 21(1): 59, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000749

RESUMO

BACKGROUND: Poplital artery transection injury is potentially catastrophic, or even life-threatening. Severe traumas, including open fracture, gunshot, stabs, and knee dislocation and complex fracture of proximal tibia or distal femur, are the common causes of high rate of amputation due to popliteal artery trauma. No report mentions vascular injury associated with minimally displaced tibial plateau fracture in adult. CASE PRESENTATION: A 30-year-old male presented with popliteal artery transection injury associated with minimally displaced tibial plateau fracture. He presented to emergency department, 6 h after fall from ground into a 1-m height hole. Physical examination suggested acute ischemia, with signs of paleness, coldness, anesthesia, hemorrhagic bullae below the right knee level. There was severe swelling and ecchymosis in popliteal fossa and around the leg with significant calf tenderness and pedal edema. Tibialis posterior, dorsalis pedis, and popliteal arterial pulses were not palpable. Radiograph suggested minimally displaced tibial plateau fracture with no evidence of knee dislocation. The patient was taken up for emergency surgery after consultation with vascular surgeon. During the closed reduction external fixation and compartment decompression, popliteal artery trunk was found transected and end-to-end repair was performed. During the post-operational period, no complication was developed and the patient was followed-up for 1 year. At the one-year follow-up, he acquired good stability of his right knee with full range of motion. CONCLUSION: Significant swelling and ecchymosis should alert the surgeons to the possibility of vascular injury in knee joint injury, even if there is no fracture or dislocation, or fracture is minimally displaced.

4.
Am J Physiol Cell Physiol ; 318(1): C73-C82, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31577514

RESUMO

Our objective was to investigate the role of primary cilia in low-magnitude, high-frequency vibration (LMHFV) treatment of MC3T3-E1 osteoblasts (OBs). We used chloral hydrate (CH), which has a well-characterized function in chemically removing primary cilia, to elucidate the role of primary cilia in LMHFV-induced OB osteogenic responses through cell viability assay, Western blot analysis, real-time quantitative RT-PCR, and histochemical staining methods. We observed a significant, 30% decrease in the number of MC3T3-E1 OBs with primary cilia (reduced from 64.3 ± 5%) and an approximately 50% reduction in length of primary cilia (reduced from 3 ± 0.8 µm) after LMHFV stimulation. LMHFV stimulation upregulated protein expression of the bone matrix markers collagen 1 (COL-1), osteopontin (OPN), and osteoclacin(OCN) in MC3T3-E1 OBs, indicating that LMHFV induces osteogenesis. High-concentration or long-duration CH exposure resulted in inhibition of MC3T3-E1 OB survival. In addition, Western blot analysis and RT-PCR revealed that CH treatment prevented LMHFV-induced osteogenesis. Furthermore, decreased alkaline phosphate activity, reduced OB differentiation, mineralization, and maturation were observed in CH-pretreated and LMHFV-treated OBs. We showed that LMHFV induces morphological changes in primary cilia that may fine-tune their mechanosensitivity. In addition, we demonstrated the significant inhibition by CH of LMHFV-induced OB mineralization, maturation, and differentiation, which might reveal the critical role of primary cilia in the process.

5.
Res Vet Sci ; 128: 153-161, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31809972

RESUMO

Hen eggs (HEs) provide valuable nutrients for humans, including proteins, carbohydrates, lipids and vitamins. Recent studies revealed a number of novel egg-derived proteins/peptides (EDPs), and EDPs may play a crucial role in food industry and medical therapy. First, these EDPs were purified from the enzyme-catalyzed hydrolysates of egg proteins and were characterized by biochemical assays such as gel electrophoresis, HPLC, mass spectrometry, proteomic and peptideomic analysis, etc. Second, some EDPs can be used as nontoxic bio-preservatives and functional nutraceuticals for replacing harmful sodium nitrite, inhibiting foodborne pathogens, promoting metal-ion absorption and improving meat-product quality, and these new features will be widely used in the field of food production. Third, novel medical properties of EDPs comprise anti-oxidative, anti-microbial, anti-inflammatory and anti-nociceptive activities, which will benefit prevention of cardiovascular diseases, cancers, diabetic mellitus, immune disorders, etc. In summary, this review gives a real insight into the novel nutritional, biological and medical functions of EDPs, predictably facilitating the applications of EDPs in production of nutritive supplements, functional nutraceuticals and therapeutic medicines.

6.
Oncol Lett ; 18(6): 6509-6515, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31807171

RESUMO

Glioma is the most common type of malignant brain tumor, and is characterized by invasive growth and chemoradiotherapy resistance. The following Cancer Genome Atlas mutation subtypes were identified in initial high-grade gliomas and recurrent gliomas treated by chemoradiotherapy: Isocitrate dehydrogenase 1/2 (IDH1/2) mutation, epidermal growth factor receptor variant III (EGFRvIII) mutation, tumor protein P53 mutation, PTEN mutation, O6-methylguanine-DNA methyltransferase promoter methylation and telomerase reverse transcriptase (TERT) mutation. The expression profile of 58 receptor tyrosine kinases (RTKs) were also examined. It was revealed that the proneural tumor subtype and IDH1/2 mutation are more frequent in recurrent tumors compared with initial tumors. Lower frequencies of the classical subtype, EGFRvIII mutation and TERT mutation were identified in recurrent tumors. A set of six RTK genes in which the level of expression was influenced by chemoradiotherapy was identified. Survival analysis revealed that the expression of several RTKs, including apoptosis-associated tyrosine kinase, fibroblast growth factor receptor 1 and insulin-like growth factor 1 receptor (IGF1R), was associated with patient survival. The stimulation of glioma cells by IGF1 in vitro was found to decreased the viability of the cells following treatment with temozolomide (TMZ). In addition, the expression level of IGF1R was increased in glioma cells treated with TMZ. These data suggest that altered RTK expression levels may influence the sensitivity of glioma to chemoradiotherapy.

7.
Sci Total Environ ; 689: 1388-1395, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31466174

RESUMO

Occurrences of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in tree bark from four species were investigated. Species-dependent congener distribution patterns were firstly reported for perfluorocarboxylic acids (PFCAs) and perfluoroalkyl sulfonic acids (PFSAs). The majority of PFSAs and PFCAs in Chinese red pine bark were C5-C7 PFSAs and perfluorohexanoic acid (PFHxA, containing six carbon atoms, C6), whereas perfluorobutanesulfonic acid (PFBS, C4) and longer chain congeners (PFCAs: C ≥ 7; PFSAs: C ≥ 8) took a larger proportion in the fissured bark from Canadian poplar, Chinese scholartree and weeping willow. The species-dependent congener profiles depended on the structures and chemical compositions of tree bark, as well as the translocation of PFASs within plants. Different tree bark characteristics caused different retention abilities for particle-bound and gaseous PFASs. Particle-bound PFASs retained in the rougher structures of fissured bark led to preferential retention of long chain congeners (the major fraction in the particle phase), while lipid-rich Chinese red pine bark retained more gaseous PFASs (mainly short chain congeners). Besides, the abundance of short chain PFASs in red pine bark was consistent with the chain length-dependent translocation behaviors of PFASs in various plants, suggesting that translocation of PFASs within plants to tree bark may be invovled.


Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental , Fluorcarbonetos/análise , Ácidos Alcanossulfônicos/análise , Canadá , Caproatos , Caprilatos , Casca de Planta/química , Ácidos Sulfônicos
8.
Oncol Lett ; 18(1): 359-367, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31289507

RESUMO

Accumulating evidence has revealed that survivin expression is associated with a malignant phenotype and poor prognosis in glioma. Survivin is also a potential target of microRNA (miRNA/miR)-218. The aim of the present study was to investigate the expression and function of survivin in glioblastoma, and to examine the association between survivin and miR-218. For that purpose, survivin mRNA levels were analyzed in 144 frozen samples of glioblastoma using whole-genome RNA sequencing. In vitro cell proliferation, migration, invasion and apoptosis assays were performed, and survivin expression was detected by western blotting. The results revealed that the mRNA expression levels of survivin were negatively and significantly associated with overall survival in glioblastoma. Further in vitro analyses suggested that miR-218 may inhibit the expression of survivin. Expression of miR-218 in the LN229 cell line was significantly lower than that in the immortalized human gliocyte HEB cell line. miR-218 markedly inhibited tumor cell proliferation, migration and invasion capacities, and decreased apoptosis. miR-218 also inhibited the expression of survivin. These results indicated that survivin may be a target of miR-218 and could serve as a predictive biomarker.

9.
Oncol Lett ; 18(1): 386-394, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31289510

RESUMO

Glioblastoma multiforme (GBM) is the most common and malignant type of glioma, with a poor prognosis for patients. The survival time of patients varies greatly due to the complexity of the human genome, which harbors diverse oncogenic drivers. In order to identify the specific driving factors, 325 glioma samples from the Chinese Glioma Genome Atlas (CGGA) database were analyzed in the present study. The level of RELB proto-oncogene, NF-κß subunit (RELB) expression increased with the pathological grade progression of the gliomas, and higher expression levels were present in the mesenchymal subtype and isocitrate dehydrogenase 1 (IDH1) wild-type gliomas. This RELB expression pattern was identified in the CGGA database and observed in three large independent databases. In patients with GBM from the CGGA database, a higher RELB expression level was associated with a shorter survival time, a mesenchymal subtype and IDH1 wild-type gliomas. Kaplan-Meier survival analysis, survival nomograms and Cox analysis demonstrated an independent prognostic value for RELB expression. Moreover, biological function analysis indicated the association of RELB with the 'immune response', 'cell activation' and the 'apoptotic process'. In addition, RELB expression levels exhibited a negative correlation with the levels of microRNA (miR)-139-5p and miR-139-3p. The present study identified the pathological and biological roles of RELB in glioma and revealed its independent prognostic effect. These results suggested that RELB may be used as a prognostic biomarker and potential therapeutic target in glioma.

10.
J Synchrotron Radiat ; 26(Pt 4): 1115-1126, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31274435

RESUMO

Here a direct comparison is made between various X-ray wavefront sensing methods with application to optics alignment and focus characterization at X-ray free-electron lasers (XFELs). Focus optimization at XFEL beamlines presents unique challenges due to high peak powers as well as beam pointing instability, meaning that techniques capable of single-shot measurement and that probe the wavefront at an out-of-focus location are desirable. The techniques chosen for the comparison include single-phase-grating Talbot interferometry (shearing interferometry), dual-grating Talbot interferometry (moiré deflectometry) and speckle tracking. All three methods were implemented during a single beam time at the Linac Coherent Light Source, at the X-ray Pump Probe beamline, in order to make a direct comparison. Each method was used to characterize the wavefront resulting from a stack of beryllium compound refractive lenses followed by a corrective phase plate. In addition, difference wavefront measurements with and without the phase plate agreed with its design to within λ/20, which enabled a direct quantitative comparison between methods. Finally, a path toward automated alignment at XFEL beamlines using a wavefront sensor to close the loop is presented.

11.
Soft Matter ; 15(28): 5760-5769, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31282526

RESUMO

The structure of a hard film mounted on a soft viscoelastic substrate exists widely in nature and in industrial production, in which the hard film plays an important role. In this study, in order to accurately describe the indentation behaviors of hard film/soft viscoelastic substrate systems and to separate the mechanical properties of the hard film from the overall indentation response, an analytical relationship between the indentation loads and displacements was derived and presented herein based on plate theory, Hankel transformation, the elastic-viscoelastic correspondence principle, and Boltzmann superposition principle. In addition, finite element simulations and experiments were performed to investigate the effectiveness and applicability of the theoretical model. The results showed that the analytical solution agreed extremely well with the experiments and simulations. By analyzing the analytical solution, it was found that, due to the presence of the hard film, the viscous behaviors of the hard film/soft viscoelastic substrate system depended not only on the viscous properties of the soft substrate but also on the elastic properties of the soft substrate. Surprisingly, the relaxation time of the hard film/soft viscoelastic substrate system became longer than that of the soft substrate, but the ratio of the decay modulus to the equilibrium modulus was lower than that of the soft substrate. The above findings remind us that it is impossible to simply judge whether the hard film inhibits or promotes the soft substrate viscous behaviors. Our research can help readers gain insights into the indentation response characteristics of hard film/soft viscoelastic substrate systems, and it provide a theoretical basis for the measurement of the mechanical properties of a hard film mounted on a soft viscoelastic substrate.

12.
Chin Med J (Engl) ; 132(17): 2073-2078, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31261204

RESUMO

BACKGROUND: Rapid visual acuity (VA) decline was a common complaint in patients with sellar/suprasellar germinoma. In our hospital, 3.4 Gy/2f of emergency irradiation was applied to save patient VA and enable subsequent chemoradiotherapy. This study aimed to investigate the efficacy of emergency irradiation with 3.4 Gy/2f in patients with sellar/suprasellar germinoma who had rapid VA decline. METHODS: From January 2014 to December 2017, 33 patients with sellar/suprasellar germinoma who complained of VA decline within 3 months received 3.4 Gy/2f of emergency irradiation in Beijing Tiantan Hospital. The best-corrected VA (BCVA) and mean deviation (MD) were measured. Correlations between visual function change and clinical factors, including age at diagnosis, duration of VA decline, extent of tumor regression, serum level of tumor markers, were analyzed. RESULTS: Among 33 patients with sellar/suprasellar germinoma, the median diameter and volume of sellar/suprasellar lesions were 32 mm (range: 5-55 mm) and 12.9 cm (range 0.6-58.5 cm), respectively. Data on pre- and post-emergency-irradiation BCVA were obtained in 32 patients. For the right eyes, BCVA was improved in 23 patients (71.9%), unchanged in 7 (21.9%), and worsened in 2 (6.2%); and for the left eyes, these numbers were 27 (84.4%), 4 (12.5%), and 1 (3.1%), respectively. In terms of the logarithm of the minimum angle of resolution (logarithm of the minimum angle of resolution = Log (1/BCVA) score, the improvement was significant in both eyes (P < 0.001). In terms of MD, six patients had paired data and the improvement was marginal in the right eyes (P = 0.068) and significant in the left eyes (P = 0.043). However, no clinical factor was found to have correlation with visual function improvement. CONCLUSION: In sellar/suprasellar germinoma patients with VA decline, 3.4 Gy/2f of emergency irradiation was effective in improving visual function.


Assuntos
Germinoma/tratamento farmacológico , Germinoma/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Gonadotropina Coriônica/metabolismo , Tratamento Farmacológico , Humanos , Radioterapia , Estudos Retrospectivos , Acuidade Visual/efeitos dos fármacos , Acuidade Visual/fisiologia , Acuidade Visual/efeitos da radiação , Adulto Jovem
13.
J Transl Med ; 17(1): 228, 2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315634

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is a universal chronic disease in China. The balance of the gut microbiome is highly crucial for a healthy human body, especially for the immune system. However, the relationship between the gut microbiome and CKD has not yet been clarified. METHODS: A total of 122 patients were recruited for this study. Among them, 24 patients were diagnosed with CKD5 but did not receive hemodialysis therapy, 29 patients were diagnosed with CKD5 and received hemodialysis therapy and 69 were matched healthy controls. The gut microbiome composition was analyzed by a 16S rRNA (16S ribosomal RNA) gene-based sequencing protocol. High-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC/ESI-MS/MS) technology was used to evaluate the levels of microbiome-related protein-binding uremic toxins level, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), in the patients. RESULTS: We compared the gut microbiome results of 122 subjects and established a correlation between the gut microbiome and IS and PCS levels. The results indicated that alpha and beta diversity were different in patients with CKD5 than in the healthy controls (p < 0.01). In comparison to healthy controls, CKD5 patients exhibited a significantly higher relative abundance of Neisseria (p < 0.001), Lachnoclostridium (p < 0.001) and Bifidobacterium (p < 0.001). Faecalibacterium (p < 0.001) displayed a notably lower relative abundance for CKD5 patients both with and without hemodialysis than for controls. It was also found that the concentrations of IS and PCS were correlated with the gut microbiome. CONCLUSIONS: Our results indicate that CKD5 patients both with and without hemodialysis had dysbiosis of the gut microbiome and that this dysbiosis was associated with an accumulation of IS and PCS. These results may support further clinical diagnosis to a great extent and help in developing potential probiotics to facilitate the treatment of CKD5.

14.
Environ Sci Technol ; 53(13): 7473-7482, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31244074

RESUMO

Bromophenols occur naturally and are used globally as man-made additives in various industrial products. They are decomposition products of many emerging organic pollutants, such as tetrabromobisphenol A, polybrominated dibenzo- p-dioxin (PBDD), polybrominated diphenyl ethers (PBDE), and others. To characterize their biotransformation pathways, bromophenol congener 2,4,6-tribromophenol, being used most frequently in the synthesis of brominated flame retardants and having the greatest environmental abundance, was selected to hydroponically expose rice plants. After exposure for 5 days, 99.2% of 2,4,6-tribromophenol was metabolized by rice. Because of the lack of relative reference standards, an effective screening strategy was used to screen for potential metabolites that were further qualitatively identified by gas and liquid chromatography combined with high-resolution mass spectrometry. Forty transformation products were confirmed or tentatively identified at different confidence levels, including 9 phase I and 31 phase II metabolites. A large number of metabolites (39) were found in rice root, and 10 of them could be translocated and detected in rice stems or leaves. Many transformation pathways were proposed, including debromination, hydroxylation, methylation, coupling reactions, sulfation, and glycosylation. It was remarkable that a total of seven hydrophobic, persistent, and toxic OH-PBDEs and PBDD/Fs were found, indicating the biotic dimeric reactions of 2,4,6-tribromophenol that occurred in the rice plants. These results improve our understanding of the transformation and environmental fates of bromophenols, and they indicate new potential sources for OH-PBDEs and PBDD/Fs in the environment, especially in food chains.


Assuntos
Oryza , Éteres Difenil Halogenados , Redes e Vias Metabólicas , Fenóis
15.
CNS Neurosci Ther ; 25(9): 965-975, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31180187

RESUMO

BACKGROUND: Glioma is the most common and aggressive type of primary brain tumor in adults. Although radiotherapy and chemotherapy are used in the treatment of glioma, survival remains unsatisfactory. Chemoresistance is one of the primary reasons for the poor prognosis of glioma. Several studies have demonstrated that glioma stem cells (GSC) may be one of the reasons for chemoresistance. In this article, we attempt to search for a new biomarker related to GSC and chemoresistance in glioma. METHODS: We used three datasets (GSE23806, COSMIC, and CGGA) to search for the genes related to GSC, temozolomide (TMZ) resistance, and overall survival. The selected gene was investigated with respect to the relationship between mRNA levels and clinical characteristics in the CGGA and TCGA dataset. Gene ontology (GO) analysis was used for bioinformatics analysis. Kaplan-Meier survival analysis and Cox regression analysis were used for survival analysis. RESULTS: The transmembrane protein 71 (TMEM71) gene was selected for further research. TMEM71 was highly expressed in GSCs and TMZ-resistant cells. The TMEM71 mRNA levels increased with increasing grades of glioma. In IDH-wild-type and MGMT-unmethylated samples, TMEM71 was overexpressed. The TMEM71 transcript levels were also increased significantly in mesenchymal subtype gliomas. GO analysis demonstrated that TMEM71 was related to the immune and inflammatory responses, cell proliferation, cell migration, chemotaxis, and the response to drugs. Specifically, PD-1, PD-L1, TIM-3, and B7-H3 were tightly associated with TMEM71 expression. This result indicates that TMEM71 may play an important role in the immune response. More importantly, high expression of TMEM71 was correlated with short survival time in both glioma and glioblastoma patients. CONCLUSION: In summary, TMEM71 expression was increased in GBM and associated with immune response. Our study suggests that TMEM71 may function as an oncogene and serve as a new effective therapeutic target for the treatment of glioma.

16.
Front Chem ; 7: 188, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31024884

RESUMO

A series of thermally activated delayed fluorescence (TADF) exciplex based on the TX-TerPy were constructed. The electronic coupling between the triplet local excited states (3LE) of the donors and acceptor and the charge transfer states had a great influence on the triplet exciton harvesting and ΦPL. Herein, based on this strategy, three donor molecules TAPC, TCTA, and m-MTDATA were selected. The local triplet excited state (3LE) of the three donors are 2.93, 2.72 and 2.52 eV in pure films. And the 3LE of TX-TerPy is 2.69 eV in polystyrene film. The energy gap between the singlet charge transfer (1CT) states of TAPC:TX-TerPy (7:1), TCTA:TX-TerPy (7:1) and the 3LE of TX-TerPy are 0.30 eV and 0.20 eV. Finally, the ΦPL of TAPC:TX-TerPy (7:1) and TCTA:TX-TerPy (7:1) are 65.2 and 69.6%. When we changed the doping concentration of the exciplex from 15% to 50%, the ratio of the triplet decreased, and ΦPL decreased by half, perhaps due to the increased energy gap between 1CT and 3LE. Therefore, optimizing the 1CT, 3CT, and 3LE facilitated the efficient exciplex TADF molecules.

17.
Exp Ther Med ; 17(2): 1300-1305, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30680006

RESUMO

Hdac2/Inpp5f on the therapeutic effect of pregabalin on neuropathic pain in chronic constriction injury (CCI) rats was investigated. A total of 90 healthy SD rats were selected and divided into the treatment group, the model control group and the normal control group with 30 rats in each group. Rats in the treatment and model control groups were used to construct CCI model. The control group was treated with sham surgery. The model control group was not treated after surgery. The treatment group was treated with pregabalin on the 8th day after operation. Behavioral experiments were performed to measure mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). The expression of inflammatory cytokines TNFα and IL-1ß was detected by ELISA kit and expression of Hdac2 and Inpp5f mRNA was detected by RT-qPCR. Before treatment, compared with the normal control group, MWT and TWL values of the treatment and model control groups were significantly decreased (P<0.05). At different time-points after treatment, MWT and TWL were higher in the treatment group than in the model control group and were lower than in the normal control group. At 21 days after operation, the levels of TNFα and IL-1ß in the model control and treatment groups were higher than those in the normal control group (P<0.05). The expression level of Hdac2 was higher in the treatment group than in the normal control group (P<0.05). The expression level of Inpp5f mRNA in the treatment and normal control groups was significantly higher than that in the model control group (P<0.05), but the expression level of Inpp5f mRNA in the treatment group was lower than that in the normal control group (P<0.05). Therefore, pregabalin can effectively relieve neuropathic pain in CCI rats, and its efficacy is related to Hdac2 and Inpp5f. Our study provides reference for clinical treatment of neuropathic pain induced by CCI.

18.
Cancer Lett ; 443: 91-107, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30529153

RESUMO

Despite the clinical success of temozolomide (TMZ), its sensitivity remains a major challenge in glioblastoma (GBM). Here, we show that PLK4 affects TMZ sensitivity by regulating the IKBKE/NF-κB axis. The mRNA level of PLK4 was significantly associated with glioma grade progression and inversely correlated with overall survival (OS) in patients with high-grade gliomas (HGG). Further analyses indicated that GBM patients with low PLK4 expression levels gained greater survival benefits from chemotherapy than did those with high PLK4 expression. In GBM cells, TMZ sensitivity was decreased by ectopic expression of PLK4 and enhanced by depletion of PLK4. In the GBM mice model, inhibiting PLK4 in combination with chemotherapy slowed tumor growth and provided a significant survival benefit. Furthermore, PLK4 interacted with and phosphorylated IKBKE, leading to an increase in NF-κB transcriptional activity and anti-apoptosis. Notably, the PLK4 inhibitor CFI400945, which is currently in clinical trials, had a synergistic effect with TMZ, increasing TMZ sensitivity in xenografts from patient-derived primary GBMs. Our work describes the PLK4-IKBKE signaling axis that influences GBM proliferation and chemosensitivity, and can enhance the anti-tumor effects of chemotherapy via therapeutic targeting.


Assuntos
Neoplasias Encefálicas/patologia , Resistencia a Medicamentos Antineoplásicos , Glioblastoma/patologia , Quinase I-kappa B/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Adolescente , Adulto , Idoso , Animais , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Criança , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Regulação Neoplásica da Expressão Gênica , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Indazóis/administração & dosagem , Indazóis/farmacologia , Indóis/administração & dosagem , Indóis/farmacologia , Masculino , Camundongos , Pessoa de Meia-Idade , Fosforilação , Prognóstico , Análise de Sobrevida , Temozolomida/administração & dosagem , Temozolomida/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem
19.
Cell ; 175(6): 1665-1678.e18, 2018 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-30343896

RESUMO

Low-grade gliomas almost invariably progress into secondary glioblastoma (sGBM) with limited therapeutic option and poorly understood mechanism. By studying the mutational landscape of 188 sGBMs, we find significant enrichment of TP53 mutations, somatic hypermutation, MET-exon-14-skipping (METex14), PTPRZ1-MET (ZM) fusions, and MET amplification. Strikingly, METex14 frequently co-occurs with ZM fusion and is present in ∼14% of cases with significantly worse prognosis. Subsequent studies show that METex14 promotes glioma progression by prolonging MET activity. Furthermore, we describe a MET kinase inhibitor, PLB-1001, that demonstrates remarkable potency in selectively inhibiting MET-altered tumor cells in preclinical models. Importantly, this compound also shows blood-brain barrier permeability and is subsequently applied in a phase I clinical trial that enrolls MET-altered chemo-resistant glioma patients. Encouragingly, PLB-1001 achieves partial response in at least two advanced sGBM patients with rarely significant side effects, underscoring the clinical potential for precisely treating gliomas using this therapy.


Assuntos
Neoplasias Encefálicas , Éxons , Glioblastoma , Mutação , Inibidores de Proteínas Quinases , Proteínas Proto-Oncogênicas c-met , Animais , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Sistemas de Liberação de Medicamentos , Feminino , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Inibidores de Proteínas Quinases/farmacocinética , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Proto-Oncogênicas c-met/metabolismo , Ratos Sprague-Dawley , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
20.
J Int Med Res ; 46(11): 4506-4517, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30185089

RESUMO

OBJECTIVE: To compare the clinical efficacy of cyclophosphamide (CTX) and cyclosporine A (CSA) in initial treatment of children with steroid-resistant nephrotic syndrome (SRNS). METHODS: Prospectively maintained databases were reviewed to retrospectively compare two cohorts with SRNS that received peroral administration of 2 to 2.5 mg/kg/d CTX for 3 to 6 months or 1 to 5 mg/kg/d CSA for 2 years until the primary analysis cut-off date during 2007 to 2011. The time to first on-study relapse of SRNS was the primary endpoint. The effective rate was the second endpoint. RESULTS: A total of 127 children with SRNS were included (CTX-treated cohort: n = 62; CSA-treated cohort: n = 65), with a mean 5-year follow-up. CTX-treated children showed a significantly delayed time to first on-study relapse of SRNS compared with CSA-treated children (hazard ratio 0.66, 95% confidence interval 0.32-1.75). The relapse rate (rate/year) in CTX-treated children (1.1 ± 0.1) at the 24-month follow-up was significantly higher than that with CSA (0.4 ± 0.2). This difference persisted until the final follow-up. CONCLUSIONS: CSA is associated with a significantly lower relapse rate and significantly higher effective rate compared with CTX, especially in children with minimal change disease.


Assuntos
Ciclofosfamida/uso terapêutico , Ciclosporina/uso terapêutico , Síndrome Nefrótica/tratamento farmacológico , Esteroides/efeitos adversos , Criança , Ciclofosfamida/efeitos adversos , Ciclosporina/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Síndrome Nefrótica/patologia , Recidiva , Indução de Remissão , Estudos Retrospectivos
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