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1.
Med Princ Pract ; 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33823519

RESUMO

OBJECTIVE: HER-2 positive breast cancer has a high risk of for relapse, metastasis and drug resistance, and is related to a poor prognosis. Thus, the study objective was to determine a target gene and explore the associated molecular mechanisms in HER-2 positive breast cancer. METHODS: Three RNA expression profiles were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), and were used to identify differentially expressed genes (DEGs) using R software. A Protein-Protein Interaction (PPI) network was constructed and hub genes were determined. Subsequently, the relationship between clinical parameters and hub genes was examined to screen target gene. Next, DNA methylation and genomic alterations of the target gene were evaluated. To further explore potential molecular mechanisms, genes co-expressed with the target gene were performed functional enrichment analysis Results: The differential expression analysis revealed 217 DEGs in HER-2 positive breast cancer tissues compared to normal breast tissues. RRM2 was the only hub gene closely associated with lymphatic metastasis and prognosis in HER-2 positive breast cancer. Additionally, RRM2 was frequently often amplified and negatively associated with the methylation level. Functional enrichment analysis showed that the co-expression genes were mainly involved in cell cycle. CONCLUSIONS: The present study identified RRM2 as a target gene associated with the initiation, progression and prognosis of HER-2 positive breast cancer, which may contribute to provide a new biomarker and therapeutic target.

2.
Korean J Intern Med ; 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33430574

RESUMO

Background/Aims: Coenzyme Q10 (CoQ10), is a promising antioxidant; however, low bioavailability owing to lipid-solubility is a limiting factor. We developed water-soluble CoQ10 (CoQ10-W) and compared its effects with conventional lipid-soluble CoQ10 (CoQ10-L) in an experimental model of chronic tacrolimus (Tac) nephropathy. Methods: CoQ10-W was developed from a glycyrrhizic-carnitine mixed layer CoQ10 micelle based on acyltransferases. Chronic nephropathy was induced in rats with 28-day Tac treatment; they were concomitantly treated with CoQ10-L or CoQ10-W. CoQ10 level in plasma and kidney were measured using liquid chromatography-mass spectrometry. CoQ10-W and CoQ10-L effects on Tac-induced nephropathy were assessed in terms of renal function, histopathology, oxidative stress, and apoptotic cell death. Their effects on cell viability and reactive oxygen species (ROS) production were assessed in cultured proximal tubular cells, human kidney 2 (HK-2) cells. Results: The plasma CoQ10 level was significantly higher in the CoQ10-W group than in the CoQ10-L group. Tac treatment caused renal dysfunction, typical pathologic lesions, and oxidative stress markers. Serum creatinine was restored in the Tac + CoQ10-L or CoQ10-W groups compared with that in the Tac group. CoQ10-W administration reduced oxidative stress and apoptosis markers. Mitochondrial ultrastructure assessment revealed that the addition of CoQ10-L or CoQ10-W with Tac increased mitochondrial size and number than Tac treatment alone. In vitro investigations revealed that both CoQ10-L and CoQ10-W improved cell viability and reduced ROS production in the Tac-induced HK-2 cell injury. Conclusions: CoQ10-W has a better therapeutic effect in Tac-induced renal injury than conventional CoQ10-L, possibly associated with improved CoQ10 bioavailability.

3.
PLoS One ; 16(1): e0238085, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33481789

RESUMO

Ratooning is an important cultivation practice in sugarcane production around the world, with underground buds on the remaining stalk acting as the source for establishment of a subsequent ratoon crop. However, the optimal depth of cutting during harvest in terms of yield and root growth remains unknown. We carried out a two-year field study to determine the effects of three cutting depths (0, 5 and 10 cm below the surface) ratoon cane root and yield. Results showed that cutting to a depth of 5 cm increased the root fresh weight and root volume by 21-59% and 41-127%, respectively, compared to cutting depths of 0 and 10 cm. Remarkably, cutting to a depth of 5 cm also had a significant effect on the development of fine roots, which is closely linked to cane yield. The effect was particularly noticeable in terms of two root traits, root volume and the surface area of roots with a diameter of 1.0-2.0mm, and root length and the number of root tips in roots with a diameter of 0-0.5mm. As a result, a cutting depth of 5 cm below the surface increased cane yield by 43 and 28% compared to depths of 0 and 10 cm below the surface, respectively. Overall, these findings suggest that a cutting depth of 5 cm is optimal in terms of sugarcane yield, largely due to the enhanced effect on root traits, especially the development of fine roots. These findings will help optimize sugarcane ratoon management and improve the ratoon cycle.

4.
Mol Cell Biol ; 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33288643

RESUMO

The aim of current study was to explore the mechanism of miR-142-5p in cervical cancer through mediating the PIK3AP1/P13K/AKT axis. To this end, RT-qPCR and Western blot analysis results revealed that miR-142-5p was poorly expressed, whereas PIK3AP1 was highly expressed in cervical cancer tissues and cells. Furthermore, miR-142-5p was hypermethylated in cervical cancer, as reflected by MS-PCR and ChIP assessment of enrichment of DNMT1/DNMT3a/DNMT3b in the promoter region of miR-142-5p. A target binding relationship between miR-142-5p and PIK3AP1 was established, showing that miR-142-5p targeted and inhibited the expression of PIK3AP1. Loss- and gain- function assays were conducted to determine the roles of miR-142-5p and PIK3AP1 in cervical cancer cells. CCK-8, flow cytometry and Transwell assay results revealed that overexpression of miR-142-5p in cervical cancer cells downregulated PIK3AP1 and inhibited the P13K/AKT signaling pathway, leading to reduced proliferation, migration, and invasion capacity of cervical cancer cells, but enhanced apoptosis. Collectively, epigenetic regulation of miR-142-5p targeted PIK3AP1 to inactivate the P13K/AKT signaling pathway, thus suppressing development of cervical cancer, which presents new targets for the treatment of cervical cancer.

5.
J BUON ; 25(5): 2255-2264, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33277843

RESUMO

PURPOSE: Of all breast cancers, triple-negative and HER-2 positive are the most aggressive breast cancer subtypes with a high risk of recurrence and worse prognosis. The study's purpose was to further assess the molecular mechanisms underlying aggression of breast cancer. METHODS: The microarray gene expression datasets of GSE29431 and GSE53752 were obtained from the GEO (Gene Expression Omnibus) database, which include HER-2 positive breast cancer, triple-negative breast cancer (TNBC) and normal breast tissue samples. Differentially expressed genes (DEGs) were determined using the LIMMA package of R software and subsequently functional enrichment analysis were performed by the ClusterProfiler package in the R platform. The STRING database was used to construct a protein-protein interaction (PPI) network. The most significant module and key genes were identified by Cytoscape software. Utilizing the Kaplan-Meier plotter and UALCAN database, we defined the key genes associated with prognotic values and molecular subtypes as invasive genes. RESULTS: In total, 428 common DEGs were identified, including 143 upregulated and 285 downregulated. GO and KEGG pathway enrichment analysis indicated that the upregulated genes were associated with mitotic nuclear division and cell cycle, whereas the downregulated genes were significantly associated with response to peptide and PPAR signaling pathway, respectively. A PPI network with 57 nodes and 335 edges was established, from which one most significant module was identified. Moreover, 12 key genes selected from the module with high degree centrality more than 21 were highly associated with high clinical aggressiveness and worse overall survival rate. CONCLUSIONS: Our studies could enhance the understanding of the molecular mechanism of breast cancer aggressiveness, and the identification of invasive key genes promoted the individualized and comprehensive treatment.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33242305

RESUMO

Environment-friendly lead-free piezoelectric materials with excellent piezoelectric properties are needed for high frequency ultrasonic transducer applications. Recently, lead-free 0.915(K0.45Na0.5Li0.05)NbO3-0.075BaZrO3-0.01(Bi0.5Na0.5)TiO3 (KNLN-BZ-BNT) textured piezoelectric ceramics have high piezoelectric response, superior thermal stability, and excellent fatigue resistance, which are promising for devices applications. In this work, the KNLN-BZ-BNT textured ceramics were prepared by tape-casting method. Microstructural morphology, phase transition and electrical properties of KNLN-BZ-BNT textured ceramics were investigated. High frequency needle type ultrasonic transducers were designed and fabricated with these textured ceramics. The tightly focused transducers have a center frequency higher than 80 MHz and a -6 dB fractional bandwidth of 52%. Such transducers were built for an f-number close to 1, and the desired focal depth was achieved by press-focusing technology associated with a set of customer design fixture. Its lateral resolution was better than 90 µm by scanning a 15 µm tungsten wire target. These promising results demonstrate that the lead-free KNLN-BZ-BNT textured ceramic is a good candidate for high frequency ultrasonic transducer applications.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33211963

RESUMO

An approach to the design of iridium(III)-contained polytetraphenylethene Pdots that could exhibit highly efficient electrochemiluminescence (ECL) was proposed. The relationships of ECL performance between the iridium complex-embedded and end-capped aggregation-induced emission (AIE) active Pdots in aqueous media were investigated for the first time. The iridium complexes with cyclometalated ligand 6-phenylphenanthridine (pphent) were incorporated into the copolymers by either embedding (P0, P2-P5) or end-capping (P1) into the backbone via an ancillary 2,2'-bipyridine (bpy) ligand. Subsequently, the corresponding Pdots of P0-P5 encapsulated with poly(styrene-co-maleicanhydride) could be obtained by the nanoprecipitation method. Compared to Pdots0, Pdots2-Pdots5 with (pphent)2Ir(bpy) (M1) complex embedding, as the iridium complex content increases, ECL signals were decreased in the order of Pdots0 > Pdots2 > Pdots3 > Pdots4 > Pdots5; whereas among these Pdots of P0-P5, Pdots1 with M1 complex end-capping exhibited the highest ECL efficiency (relative to a Ru(bpy)32+ system of 18.9%) and 4.7-fold enhancement of the ECL signal compared to the parent Pdots of P0, which was mainly attributed to the good film conductivity of the completely conjugated architectures, thus prompting the intramolecular electron transfer. This work opened new avenues for designing highly efficient ECL emitters.

8.
Sci Rep ; 10(1): 18769, 2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-33127971

RESUMO

Oxidative stress (OS) is associated with poor oocyte quality and in vitro fertilization and embryo transfer (IVF-ET) outcomes for patients with polycystic ovary syndrome (PCOS). Growth hormone (GH) can function to reduce OS in some types of cells. Therefore, this prospective randomized study investigated whether GH can significantly improve OS and oocyte quality in women with PCOS. This study enrolled 109 and 50 patients with and without PCOS (controls), respectively. The patients with PCOS were randomly assigned to receive treatment with GH (PCOS-T) or not (PCOS-C). The primary outcome included markers of OS in serum and FF, and secondary outcomes were mitochondrial function in granulosa cells (GCs) and IVF-ET outcomes. The PCOS groups showed higher basal serum total oxidant status (TOS) and OS index (OSI) levels. The follicle fluid (FF) TOS and OSI and GC apoptosis rate were significantly higher, whereas the GC mitochondrial membrane potential (MMP) was significantly lower in the PCOS-C group than in the PCOS-T and non-PCOS control groups (P < 0.05). Significantly more oocytes were fertilised and cleavage stage embryos were produced in the PCOS-T group than in the PCOS-C group (P < 0.05). GH also improved the rates of implantation and clinical pregnancy, but not significantly (P > 0.05). This study showed that GH alleviated the TOS and OSI level in FF and improved GC mitochondrial dysfunction and oocyte quality in patients with PCOS.Clinical Trial Registration Number: This project was prospectively registered on the Chinese Clinical Trial Registry on October 20, 2018. (ChiCTR1800019437) ( https://www.chictr.org.cn/edit.aspx?pid=28663&htm=4 ).

9.
J Cell Mol Med ; 24(20): 12176-12187, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32924269

RESUMO

The Notch signalling pathway is involved in the development of several cancers, including colorectal cancer (CRC). However, whether mutations in this pathway could alter the CRC immunophenotype remains unknown. Here, we investigated the relationship between Notch signalling pathway mutations and the tumour immune microenvironment by analysing gene expression data from the GSE108989 single T cell RNA sequencing data set and The Cancer Genome Atlas (TCGA) data set. We found that Notch signalling pathway mutations were associated with an increased number of tumour-specific CD8+ T cells and decreased number of inhibitory regulatory T (Treg) cells, representing an enhanced anti-tumour response in the GSE108989 data set. In TCGA data set, we also found that Notch signalling pathway mutations were associated with enrichment of genes associated with immune activation pathways and higher expressions of PDCD1, GZMB and PRF1. Although Notch signalling pathway mutations did not affect the overall survival and disease-free survival of CRC patients, they were associated with earlier disease stages and lower rates of metastasis. These results demonstrated that Notch signalling pathway mutations can enhance anti-tumour immunity in CRC, as validated by the two data sets, suggesting that they may be promising biomarkers for immune checkpoint blockade therapies for CRC patients.

10.
Am J Mens Health ; 14(4): 1557988320933758, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32804026

RESUMO

A sexual abstinence period (SAP) lasting for 2-7 days is recommended before undertaking semen analyses. However, there is no consensus regarding the length of the SAP for couples using assisted reproductive technology (ART). Therefore, a meta-analysis was performed to compare the effect of short SAPs (less than 4 days) and long SAPs (4-7 days) on the clinical outcomes of fresh embryo transfer cycles after ART. A total of four studies were included in the meta-analysis. Although the fertilization rate in short SAP couples was higher than that in long SAP couples, a pooled analysis demonstrated that it was not statistically significant (p = .09). The implantation rate was, however, significantly higher in short SAP couples (p = .0001). The pooled analysis revealed that the pregnancy rate was significantly higher in short SAP couples than that in long SAP couples. The overall odds ratio (OR) for the pregnancy rate was 1.44 (p = .0006). No significant difference in miscarriage rates between the short and long SAP couples was found (p = .88). The meta-analysis indicates that a shorter abstinence period could result in higher implantation and pregnancy rates for patients undertaking ART treatments.

11.
Micromachines (Basel) ; 11(8)2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32717887

RESUMO

Piezoelectric composites are considered excellent core materials for fabricating various ultrasonic devices. For the traditional fabrication process, piezoelectric composite structures are mainly prepared by mold forming, mixing, and dicing-filing techniques. However, these techniques are limited on fabricating shapes with complex structures. With the rapid development of additive manufacturing (AM), many research fields have applied AM technology to produce functional materials with various geometric shapes. In this study, the Mask-Image-Projection-based Stereolithography (MIP-SL) process, one of the AM (3D-printing) methods, was used to build BaTiO3-based piezoelectric composite ceramics with honeycomb structure design. A sintered sample with denser body and higher density was achieved (i.e., density obtained 5.96 g/cm3), and the 3D-printed ceramic displayed the expected piezoelectric and ferroelectric properties using the complex structure (i.e., piezoelectric constant achieved 60 pC/N). After being integrated into an ultrasonic device, the 3D-printed component also presents promising material performance and output power properties for ultrasound sensing (i.e., output voltage reached 180 mVpp). Our study demonstrated the effectiveness of AM technology in fabricating piezoelectric composites with complex structures that cannot be fabricated by dicing-filling. The approach may bring more possibilities to the fabrication of micro-electromechanical system (MEMS)-based ultrasonic devices via 3D-printing methods in the future.

12.
PLoS One ; 15(7): e0235845, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32639979

RESUMO

Drought is an important factor which limits growth of sugarcane. To elucidate the physiological and biochemical mechanisms of tolerance, a pot experiment was conducted at Sugarcane Research Institute, Kaiyuan, China. Two genotypes (Yuetang 93-159-sensitive and Yunzhe 05-51-tolerant), were subjected to three treatments; 70±5% (control), 50±5% (moderate drought) and 30±5% (severe drought) of soil field capacity. The results demonstrated that drought induced considerable decline in morpho-physiological, biochemical and anatomical parameters of both genotypes, with more pronounced detrimental effects on Yuetang 93-159 than on Yunzhe 05-51. Yunzhe 05-51 exhibited more tolerance by showing higher dry biomass, photosynthesis and antioxidant enzyme activities. Compared with Yuetang 93-159, Yunzhe 05-51 exhibited higher soluble sugar, soluble protein and proline contents under stress. Yunzhe 05-51 illustrated comparatively well-composed chloroplast structure under drought stress. It is concluded that the tolerance of Yunzhe 05-51 was attributed to improved antioxidant activities, osmolyte accumulation and enhanced photosynthesis. These findings may provide valuable information for future studies on molecular mechanism of tolerance.


Assuntos
Saccharum/genética , Aclimatação , Secas , Fotossíntese , Saccharum/fisiologia , Saccharum/ultraestrutura , Estresse Fisiológico
13.
J Biomech Eng ; 2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32507897

RESUMO

The purpose of this study was to investigate how sagittal split ramus osteotomy (SSRO) and Le Fort 1 osteotomy affected the stress distribution of the temporomandibular joint (TMJ) during an anterior teeth bite using the three-dimensional (3D) finite element method. 14 orthognathic surgery patients were examined with mandibular prognathism, facial asymmetry and mandibular retraction. They underwent Le Fort 1 osteotomy in conjunction with SSRO. In addition, 10 asymptomatic subjects were recruited as the control group. The 3D models of the mandible, disc and maxilla were reconstructed according to cone-beam computed tomography (CBCT). Contact was used to simulate the interaction of the disc-condyle, disc-temporal bone, and upper-lower dentition. Muscle forces and boundary conditions corresponding to the anterior occlusions were applied on the models. The stresses on the articular disc and condyle in the preoperative group were significantly higher than normal. The contact stress and minimum principal stress in TMJ for patients with temporomandibular disorder (TMD) were abnormally higher. The peak stresses of the TMJ of the patients under anterior occlusions decreased after bi-maxillary osteotomy. No postoperative TMD symptoms were found. Maxillofacial deformity led to excessive stress on the TMJ. Bi-maxillary osteotomy can partially improve the stress distributions of the TMJ and relieve the symptoms of TMD.

14.
Int J Radiat Biol ; 96(8): 972-979, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32394793

RESUMO

Background: The value of relative biological effectiveness of tritium increases at low dose domain, which results in the suspicion of weighting factor of 1 for tritium after low dose exposure. Thus, present study was carried out to analyze the differences in the cellular responses at early and late period between low dose of tritium ß-rays and γ-rays radiation.Methods: MCF-10A cells were exposed to low dose of tritium ß-rays or γ-rays, then cellular behaviors, such as DNA double strand breaks (DSBs), apoptosis, reactive oxygen species (ROS) level and inflammatory relevant gene expression were analyzed at early and late period post-irradiation.Results: At early period the elimination of DSB foci produced by HTO is longer than γ-rays. High ROS level and a continual change of cell cycle distribution are observed in HTO radiation group. Based on the results of RNA sequencing, Ingenuity Pathway Analysis (IPA) indicates TNFR1 signaling and production of nitric oxide and ROS are activated as an acute response at 24 h post radiation. Moreover, it also shows a disturbance in cholesterol biosynthesis. The results of 30 days point that there is a lasting active inflammatory response, accompanying with a persistent high expression of relevant cytokines, such as TNF and IL1R.Conclusion: Compared to an acute response induced by γ-rays, a persistent inflammatory response exists in HTO-irradiated cells when cultured for 30 days, which might be related to accumulation of tritium in the form of organically bound tritium (OBT) in cellular DNA or lipids.

15.
J Ginseng Res ; 44(3): 399-404, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32372861

RESUMO

Korean ginseng (Panax ginseng) is associated with a variety of therapeutic effects, including antioxidative, anti-inflammatory, vasorelaxative, antiallergic, antidiabetic, and anticancer effects. Accordingly, the use of ginseng has reached an all-time high among members of the general public. However, the safety and efficacy of ginseng in transplant recipients receiving immunosuppressant drugs have still not been elucidated. Transplantation is the most challenging and complex of surgical procedures and may require causation for the use of ginseng. In this regard, we have previously examined the safety, immunological benefits, and protective mechanisms of ginseng with respect to calcineurin inhibitor-based immunosuppression, which is the most widely used regimen in organ transplantation. Using an experimental model of calcineurin inhibitor-induced organ injury, we found that ginseng does not affect drug levels in the peripheral blood and tissue, favorably regulates immune response, and protects against calcineurin inhibitor-induced nephrotoxicity and pancreatic islet injury. On the basis of our experimental studies and a review of the related literature, we propose that ginseng may provide benefits in organ transplant recipients administered calcineurin inhibitors. Through the present review, we aimed to briefly discuss our current understanding of the therapeutic benefits of ginseng related to transplant patient survival.

16.
Acta Pharmacol Sin ; 41(12): 1597-1608, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32300244

RESUMO

Tissue kallikrein has protective function against various types of injury. In this study, we investigated whether exogenous pancreatic kininogenase (PK) conferred renoprotection in a rat model of unilateral ureteral obstruction (UUO) and H2O2-treated HK-2 cells in vitro. SD rats were subjected to UUO surgery, then PK (7.2 U/g per day, ip) was administered for 7 or 14 days. After the treatment, rats were euthanized; the obstructed kidneys were harvested for further examination. We found that PK administration significantly attenuated interstitial inflammation and fibrosis, and downregulated the expression of proinflammatory (MCP-1, TLR-2, and OPN) and profibrotic (TGF-ß1 and CTGF) cytokines in obstructed kidney. UUO-induced oxidative stress, closely associated with excessive apoptotic cell death and autophagy via PI3K/AKT/FoxO1a signaling, which were abolished by PK administration. We further showed that PK administration increased the expression of bradykinin receptors 1 and 2 (B1R and B2R) mRNA and the production of NO and cAMP in kidney tissues. Coadministration with either B1R antagonist (des-Arg9-[Leu8]-bradykinin) or B2R antagonist (icatibant) abrogated the renoprotective effects of PK, and reduced the levels of NO and cAMP in obstructed kidney. In H2O2-treated HK-2 cells, addition of PK (6 pg/mL) significantly decreased ROS production, regulated the expression of oxidant and antioxidant enzymes, suppressed the expression of TGF-ß1 and MCP-1, and inhibited cell apoptosis. Our data demonstrate that PK treatment protects against the progression of renal fibrosis in obstructed kidneys.

17.
Korean J Intern Med ; 35(6): 1443-1456, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32279476

RESUMO

BACKGROUND/AIMS: Coenzyme Q10 (CoQ10) has antioxidant effects and is commercially available and marketed extensively. However, due to its low bioavailability, its effects are still controversial. We developed a water-soluble CoQ10-based micelle formulation (CoQ10-W) and tested it in an experimental model of tacrolimus (TAC)-induced diabetes mellitus (DM). METHODS: We developed CoQ10-W from a glycyrrhizic-carnitine mixed layer CoQ10 micelle preparation based on acyltransferases. TAC-induced DM rats were treated with either lipid-soluble CoQ10 (CoQ10-L) or CoQ10-W for 4 weeks. Their plasma and pancreatic CoQ10 concentrations were measured using liquid chromatography- tandem mass spectrometry. The therapeutic efficacies of CoQ10-W and CoQ10-L on TAC-induced DM were compared using functional and morphological parameters and their effects on cell viability and reactive oxygen species (ROS) production were also evaluated in cultured rat insulinoma cells. RESULTS: The plasma CoQ10 level was significantly increased in the CoQ10-W group compared to that in the CoQ10-L group. Intraperitoneal glucose tolerance tests and glucose-stimulated insulin secretion revealed that CoQ10-W controlled hyperglycemia and restored insulin secretion significantly better than CoQ10-L. The TAC-mediated decrease in pancreatic islet size was significantly attenuated by CoQ10-W but not by CoQ10-L. TAC-induced oxidative stress and apoptosis were significantly more reduced by CoQ10-W than CoQ10-L. Electron microscopy revealed that CoQ10-W restored TAC-induced attenuation in the number of insulin granules and the average mitochondrial area, unlike CoQ10-L. In vitro studies showed that CoQ10-L and CoQ10-W both improved cell viability and reduced ROS production in TAC-treated islet cells to a similar extent. CONCLUSION: CoQ10-W has better therapeutic efficacy than CoQ10-L in TAC-induced DM.

18.
Int J Mol Sci ; 21(2)2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31936371

RESUMO

Renal fibrosis is a common feature of all progressive chronic kidney diseases. Sirtuin 3(SIRT3) is one of the mitochondrial sirtuins, and plays a role in the regulation of mitochondrialbiogenesis, oxidative stress, fatty acid metabolism, and aging. Recently, honokiol (HKL), as apharmaceutical SIRT3 activator, has been observed to have a protective effect against pressureoverload-induced cardiac hypertrophy by increasing SIRT3 activity. In this study, we investigatedwhether HKL, as a SIRT3 activator, also has protective effects against unilateral ureteral obstruction(UUO)-induced renal tubulointerstitial fibrosis through SIRT3-dependent regulation ofmitochondrial dynamics and the nuclear factor-κB (NF-κB)/transforming growth factor-ß1 (TGF-ß1)/Smad signaling pathway. We found that HKL decreased the UUO-induced increase in tubularinjury and extracellular matrix (ECM) deposition in mice. HKL also decreased myofibroblastactivation and proliferation in UUO kidneys and NRK-49F cells. Finally, we showed that HKLtreatment decreased UUO-induced mitochondrial fission and promoted mitochondrial fusionthrough SIRT3-dependent effects. In conclusion, activation of SIRT3 via HKL treatment might havebeneficial effects on UUO-induced renal fibrosis through SIRT3-dependent regulation ofmitochondrial dynamics and the NF-κB/TGF-ß1/Smad signaling pathway.


Assuntos
Fibrose/tratamento farmacológico , Inflamação/tratamento farmacológico , Nefropatias/tratamento farmacológico , Sirtuína 3/genética , Fator de Crescimento Transformador beta1/genética , Animais , Compostos de Bifenilo/farmacologia , Linhagem Celular , Modelos Animais de Doenças , Fibrose/genética , Fibrose/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/genética , Inflamação/patologia , Nefropatias/genética , Nefropatias/patologia , Lignanas/farmacologia , Camundongos , Dinâmica Mitocondrial/efeitos dos fármacos , NF-kappa B/genética , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/genética
19.
iScience ; 23(1): 100774, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31887665

RESUMO

The aggregation-induced electrochemiluminescence (AIECL) of polyfluorene derivative nanoparticles containing tetraphenylethylene (TPE) in aqueous media is reported in this work. The TPE unit limits the intramolecular free rotation of phenyl rings, as well as the π-π stacking interactions of molecules, which significantly enhances ECL signal of the polyfluorene nanoparticles. With co-reactants of tri-n-propylamine (TPrA) and S2O82-, the copolymer nanoparticles show visualized ECL emissions at both positive and negative potentials. The ECL efficiency of copolymer nanoparticles in solid state is 163% compared with that of standard ECL species, Ru(bpy)32+. And at negative potential, the ECL intensity of copolymer nanoparticles is even stronger with 6.5 times compared with that at positive potential. The ECL generation mechanisms are analyzed detailed by annihilation and co-reactant route transient ECL test (millisecond scale). This work provides a reference for the organic structure design for AIECL and shows promising potential in luminescent device and biological applications.

20.
Korean J Intern Med ; 35(2): 400-407, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31739654

RESUMO

BACKGROUND/AIMS: It is undetermined if herbal medicines (HM) containing aristolochic acid (AA)-containing have similar nephrotoxicity to AA itself. METHODS: We administered HM containing a high concentration of AA for 5 days (short-term study) or a low concentration of AA for 30 days (long-term study) to C57BL/6 mice; for comparison, same dose of AA compound was used as controls. RESULTS: The nephrotoxicity in the HM- and AA-treated mice was compared in terms of renal function, histopathology, oxidative stress, apoptotic cell death, and mitochondrial damage. Short-term HM treatment resulted in acute kidney injury (marked renal dysfunction, acute tubular necrosis, and neutrophil gelatinase-associated lipocalin [NGAL] expression) in which the severity of renal dysfunction and histopathology was comparable with that induced by the administration of AA alone. Long-term HM treatment resulted in features of chronic kidney disease (CKD, mild renal dysfunction and tubular atrophy and dilatation). No significant differences in these parameters were observed between the HM- and AA-treated mice. HM-induced oxidative stress (8-hydroxy-2'-deoxyguanosine and manganese- dependent superoxide dismutase expression) and apoptotic cell death (terminal deoxynucleotidyl transferase dUTP nick end labelling [TUNEL]-positive cells and active caspase-3 expression) were similar in HM- and AA-treated mice in the short-term and long-term studies. Mitochondrial injury, evaluated by electron microscopy, was also similar in HM- and AA-treated mice in the short-term and long-term studies. CONCLUSION: The nephrotoxic potential of HM containing AA was similar to that of AA itself.

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