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1.
Int J Impot Res ; 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32358511

RESUMO

Growing evidence reports that chronic kidney diseases (CKD) might play a role in erectile dysfunction (ED), but limited knowledge is available. Therefore, we performed a systematic review up to 21/08/2019 to investigate the associations between CKD and ED. The main analysis reported the prevalence of ED as absolute estimates (in %) with their 95% confidence intervals (CIs) and across CKD stages (when specified), hemodialysis and transplant, calculating the p for interaction across strata. Among 291 studies, we included 34 articles with 5986 men. We found an overall prevalence of 76% (95%CI: 72-79) with a high degree of heterogeneity (I2 = 84.2%; p < 0.0001). Analyzing the data by CKD stage, we found a significant higher prevalence of ED in CKD (78%; 95%CI: 75-81%; I2 = not possible) compared with hemodialysis stage (prevalence = 77%; 95%CI: 73-80%; I2 = 84.5) or to patients undergoing transplant (prevalence = 64%; 95%CI: 54-74%; I2 = 54%) (p across strata = 0.036). Considering the high prevalence of ED in men with CKD, health care practitioners should focus on issues of sexual health in men with CKD. Given the advancements in dialysis and therapy and the associated advancements in survival and life expectancy, maintaining the patients' sexual function is important for their well-being and quality of life.

3.
J Neuroinflammation ; 17(1): 125, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32321538

RESUMO

BACKGROUND: Robust activation of glial cells has been reported to occur particularly during the pathogenesis of bone cancer pain (BCP). Researchers from our group and others have shown that histone deacetylases (HDACs) play a significant role in modulating glia-mediated immune responses; however, it still remains unclear whether HDACs are involved in the activation of glial cells during the development of BCP. METHODS: BCP model was established by intra-tibia tumor cell inoculation (TCI). The expression levels and distribution sites of histone deacetylases (HDACs) in the spinal dorsal horn and dorsal root ganglia were evaluated by Western blot and immunofluorescent staining, respectively. Suberoylanilide hydroxamic acid (SAHA), a clinically used HDAC inhibitor, was then intraperitoneally and intrathecally injected to rescue the increased expression levels of HDAC1 and HDAC2. The analgesic effects of SAHA administration on BCP were then evaluated by measuring the paw withdrawal thresholds (PWTs). The effects of SAHA on activation of glial cells and expression of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) in the spinal dorsal horn and dorsal root ganglia of TCI rats were further evaluated by immunofluorescent staining and Western blot analysis. Subsequently, the effects of SAHA administration on tumor growth and cancer cell-induced bone destruction were analyzed by hematoxylin and eosin (HE) staining and micro-CT scanning. RESULTS: TCI caused rapid and long-lasting increased expression of HDAC1/HDAC2 in glial cells of the spinal dorsal horn and dorsal root ganglia. Inhibiting HDACs by SAHA not only reversed TCI-induced upregulation of HDACs but also inhibited the activation of glial cells in the spinal dorsal horn and dorsal root ganglia, and relieved TCI-induced mechanical allodynia. Further, we found that SAHA administration could not prevent cancer infiltration or bone destruction in the tibia, which indicated that the analgesic effects of SAHA were not due to its anti-tumor effects. Moreover, we found that SAHA administration could inhibit GSK3ß activity in the spinal dorsal horn and dorsal root ganglia, which might contributed to the relief of BCP. CONCLUSION: Our findings suggest that HDAC1 and HDAC2 are involved in the glia-mediated neuroinflammation in the spinal dorsal horn and dorsal root ganglia underlying the pathogenesis of BCP, which indicated that inhibiting HDACs by SAHA might be a potential strategy for pain relief of BCP.

4.
Clin Neurophysiol ; 131(6): 1323-1331, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32304846

RESUMO

OBJECTIVE: Language experience can develop long-term memory traces for speech units in the brain, to ensure efficient processing of speech sounds. However, prelingually deafened children lack sufficient auditory input before cochlear implantation. Whether the experience-dependent long-term memory traces exist in prelingually deafened children with cochlear implants (CIs) remains unclear. METHODS: We presented CI and normal hearing (NH) children with Mandarin Chinese spoken disyllables in an oddball paradigm and recorded event-related potentials. Each disyllable was defined as a meaningful word or a meaningless pseudoword by the tonal information in the second syllable. RESULTS: The amplitude of mismatch negativity (MMN) elicited by words was larger than that elicited by pseudowords in NH children. However, this enhancement of the MMN amplitude was not found in CI children. Behavioral results showed later recognition points for words and lower accuracies for speech comprehension in CI children than in NH children. Furthermore, increased theta power for words compared with pseudowords was only found in NH children. CONCLUSIONS: Our findings indicate a deficit of long-term memory traces for words in prelingually deafened children with cochlear implants. SIGNIFICANCE: Early speech input may be crucial to the formation of long-term memory traces for speech units.

5.
Mol Genet Genomic Med ; : e1111, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32239807

RESUMO

BACKGROUND: We investigated whether a heterozygous mutation that we newly identified in HTRA1 (high-temperature requirement serine protease A1 gene) in a pedigree with autosomal dominant hereditary cerebral small vessel disease (SVD) reduces the function of HTRA1 and affects the transforming growth factor-ß1 (TGF-ß1)/Smad signaling. METHODS: Whole-exome sequence from the proband and her two sisters was examined using whole-exome enrichment and sequencing. Expression of HTRA1 and TGF-ß1/Smad and HTRA1 activity were assayed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blotting analyses after transfecting wild-type and mutant HTRA1 genes into HEK293 cells. RESULTS: A new heterozygous mutation (c.614C>G:p.Ser205Cys) in HTRA1 was identified in the sequence encoding the trypsin-like serine protease domain. The mutation was predicted to be deleterious by in silico tools. Moreover, in vitro activity and protein analyses revealed a loss-of-function effect of the mutation: the proteolytic activity of mutant HTRA1 was decreased, and, notably, this was accompanied by an increase in TGF-ß1/Smad protein levels. CONCLUSIONS: The heterozygous mutation HTRA1 S205C causing diminished protease activity is associated with-and could represent a cause of-autosomal dominant hereditary cerebral SVD. Our results also indicate a relationship between HTRA1 and TGF-ß1/Smad signaling.

6.
Stem Cell Res Ther ; 11(1): 110, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32143712

RESUMO

BACKGROUND: Although dental pulp stem cells (DPSCs) isolated from periodontally compromised teeth (P-DPSCs) have been demonstrated to retain pluripotency and regenerative potential, their use as therapeutics remains largely unexplored. In this study, we investigated the proangiogenic effects of extracellular vesicles (EVs) secreted by P-DPSCs using in vitro and in vivo testing models. METHODS: Patient-matched DPSCs derived from periodontally healthy teeth (H-DPSCs) were used as the control for P-DPSCs. Conditioned media (CMs) derived from H-DPSCs and P-DPSCs (H-CM and P-CM), CMs derived from both cell types pretreated with the EV secretion blocker GW4869 (H-GW and P-GW), and EVs secreted by H-DPSCs and P-DPSCs (H-EVs and P-EVs) were prepared to test their proangiogenic effects on endothelial cells (ECs). Cell proliferation, migration, and tube formation were assessed using the Cell Counting Kit-8 (CCK-8), transwell/scratch wound healing, and Matrigel assays, respectively. Specifically, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and western blot analysis were used to examine the expression levels of angiogenesis-related genes/proteins in ECs in response to EV-based incubation. Finally, a full-thickness skin defect model was applied to test the effects of EVs on wound healing and new vessel formation. RESULTS: Both H-CM and P-CM promoted EC angiogenesis, but the proangiogenic effects were compromised when ECs were incubated in H-GW and P-GW, wherein the EV secretion was blocked by pretreatment with GW4869. In EV-based incubations, although both H-EVs and P-EVs were found to enhance the angiogenesis-related activities of ECs, P-EVs exerted a more robust potential to stimulate EC proliferation, migration, and tube formation. In addition, P-EVs led to higher expression levels of angiogenesis-related genes/proteins in ECs than H-EVs. Similarly, both P-EVs and H-EVs were found to accelerate wound healing and promote vascularization across skin defects in mice, but wounds treated with P-EVs resulted in a quicker healing outcome and enhanced new vessel formation. CONCLUSIONS: The findings of the present study provide additional evidence that P-DPSCs derived from periodontally diseased teeth represent a potential source of cells for research and therapeutic use. Particularly, the proangiogenic effects of P-EVs suggest that P-DPSCs may be used to promote new vessel formation in cellular therapy and regenerative medicine.

7.
Sci Rep ; 10(1): 4155, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32139705

RESUMO

Malignant gliomas are the most common tumor in central nervous system with poor prognosis. Due to the limitation of histological classification in earlier diagnosis and individualized medicine, it is necessary to combine the molecular signatures and the pathological characteristics of gliomas. Lots of microRNAs presented abnormal expression in gliomas and modulated gliomas development. Exploration the miRNAs profile is helpful for the diagnosis, therapy and prognosis of gliomas. It has been demonstrated that miR-144 plays important roles in solid tumors. However, the detail mechanisms remained unrevealed. In this study, we have demonstrated the level of miR-144 decreased in glioma tissues from patients, especially in gliomas with higher grades. MiR-144 was also validated have lower expression in glioma cell lines compared with cortical neuron cell by using qRT-PCR. The in vitro functional experiment indicated miR-144 improved gliomas progression through repressing proliferation, sensitizing to chemotherapeutics and inhibiting metastasis. We further identified fibroblast growth factor 7 (FGF7) and Caveolin 2 (CAV2) were target genes of miR-144 by luciferase reporter assay and western blotting. The mechanisms study suggested forced FGF7 expression elevated Akt activation and decreased reactive oxygen species (ROS) generation. The MTT and cell cycle assay indicated miR-144 suppressed glioma cells proliferation through modulating FGF mediated Akt signaling pathway. Meanwhile, miR-144 promoted Temozolomide (TMZ) induced apoptosis in glioma cells via increasing ROS production by using FACS. On the other hand, CAV2, as another target of miR-144, accelerated glioma cells migration and invasion via promoting glioma cells EMT progress. Retrieved expression of FGF7 or CAV2 rescued the proliferation and migration function mediated by miR-144. Furthermore, the in vivo experiments in PDX models displayed the anti-tumor function of miR-144, which could be retrieved by overexpression of FGF7 and CAV2. Taken together, these findings indicated miR-144 acted as a potential target against gliomas progression and uncovered a novel regulatory mechanism, which may provide a new therapeutic strategy and prognostic indicator for gliomas.

8.
Mol Med Rep ; 21(3): 999-1010, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32016443

RESUMO

At present, the association between prognosis­associated long noncoding RNAs (lncRNAs) and mRNAs is yet to be reported in multiple myeloma (MM). The aim of the present study was to construct prognostic models with lncRNAs and mRNAs, and to map the interactions between these lncRNAs and mRNAs in MM. LncRNA and mRNA data from 559 patients with MM were acquired from the Genome Expression Omnibus (dataset GSE24080), and their prognostic values were calculated using the survival package in R. Multivariate Cox analysis was used on the top 20 most significant prognosis­associated mRNAs and lncRNAs to develop prognostic signatures. The performances of these prognostic signatures were tested using the survivalROC package in R, which allows for time­dependent receiver operator characteristic (ROC) curve estimation. Weighted correlation network analysis (WGCNA) was conducted to investigate the associations between lncRNAs and mRNAs, and a lncRNA­mRNA network was constructed using Cytoscape software. Univariate Cox regression analysis identified 39 lncRNAs and 1,445 mRNAs that were significantly associated with event­free survival of MM patients. The top 20 most significant survival­associated lncRNAs and mRNAs were selected as candidates for analyzing independent MM prognostic factors. Both signatures could be used to separate patients into two groups with distinct outcomes. The areas under the ROC curves were 0.739 for the lncRNA signature and 0.732 for the mRNA signature. In the lncRNA­mRNA network, a total of 143 mRNAs were positively or negatively associated with 23 prognosis­associated lncRNAs. NCRNA00201, LOC115110 and RP5­968J1.1 were the most dominant drivers. The present study constructed a model that predicted prognosis in MM and formed a network with the corresponding prognosis­associated mRNAs, providing a novel perspective for the clinical diagnosis and treatment of MM, and suggesting novel directions for interpreting the mechanisms underlying the development of MM.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32065106

RESUMO

BACKGROUND: Many human diseases are associated with dysregulation of HDACs. HDAC6 exhibits deacetylase activity not only to histone protein but also to non-histone proteins such as α- tubulin, HSP90, cortactin, and peroxiredoxin. These unique functions of HDAC6 have gained significant attention in the medicinal chemistry community in recent years. Thus a great deal of effort has devoted to developing selective HDAC6 inhibitors for therapy with the hope to minimize the side effects caused by pan-HDAC inhibition. OBJECTIVE: The review intends to analyze the structural feature of the scaffolds, to provide useful information for those who are interested in this field, as well as to spark the future design of the new inhibitors. METHODS: The primary tool used for patent searching is SciFinder. All patents are retrieved from the following websites: the World Intellectual Property Organization (WIPO®), the United States Patent Trademark Office (USPTO®), Espacenet®, and Google Patents. The years of patents covered in this review are between 2016 and 2019. RESULTS: Thirty-six patents from seventeen companies/academic institutes were classified into three categories based on the structure of ZBG: hydroxamic acid, 1,3,4-oxadiazole, and 1,2,4-oxadiazole. ZBG connects to the cap group through a linker. The cap group can tolerate different functional groups, including amide, urea, sulfonamide, sulfamide, etc. The cap group appears to modulate the selectivity of HDAC6 over other HDAC subtypes. CONCLUSION: Selectively targeting HDAC6 over other subtypes represents two fold advantages: it maximizes the pharmacological effects and minimizes the side effects seen in pan-HDAC inhibitors. Many small molecule selective HDAC6 inhibitors have advanced to clinical studies in recent years. We anticipate the approval of selective HDAC6 inhibitors as therapeutic agents in the near future.

10.
Aging (Albany NY) ; 12(3): 2084-2100, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-32017705

RESUMO

The dysfunction of bone marrow stromal cells (BMSCs) may be a core factor in Type 2 diabetes mellitus (T2DM) associated osteoporosis. However, the underlying mechanism is not well understood. Here, we delineated the critical role of insulin impeding osteogenesis of BMSCs in T2DM. Compared with BMSCs from healthy people (H-BMSCs), BMSCs from T2DM patient (DM-BMSCs) showed decreased osteogenic differentiation and autophagy level, and increased senescent phenotype. H-BMSCs incubated in hyperglycemic and hyperinsulinemic conditions similarly showed these phenotypes of DM-BMSCs. Notably, enhanced TGF-ß1 expression was detected not only in DM-BMSCs and high-glucose and insulin-treated H-BMSCs, but also in bone callus of streptozocin-induced diabetic rats. Moreover, inhibiting TGF-ß1 signaling not only enhanced osteogenic differentiation and autophagy level of DM-BMSCs, but also delayed senescence of DM-BMSCs, as well as promoted mandible defect healing of diabetic rats. Finally, we further verified that it was TGF-ß receptor II (TßRII), not TßRI, markedly increased in both DM-BMSCs and insulin-treated H-BMSCs. Our data revealed that insulin impeded osteogenesis of BMSCs by inhibiting autophagy and promoting premature senescence, which it should be responsible for T2DM-induced bone loss, at least in part. These findings suggest that inhibiting TGF-ß1 pathway may be a potential therapeutic target for T2DM associated bone disorders.

12.
Spine (Phila Pa 1976) ; 45(5): 292-299, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31809475

RESUMO

STUDY DESIGN: In vitro studies of the role of 17ß-estradiol (E2) and its possible targets in intervertebral disc degeneration (IDD). OBJECTIVE: To define the regulatory role of E2 in IDD and the potential mechanisms. SUMMARY OF BACKGROUND DATA: IDD has intricate etiology that is influenced by multiple risk factors. However, the underlying molecular mechanisms of occurrence and progression of IDD are not well elucidated. The degradation of extracellular matrix (ECM) has been extensively observed in IDD. E2 was found to inhibit ECM degradation in human nuleus pulposus cells (HNPCs), but the molecular mechanism remained to be determined. METHODS: Western blot and qPCR was performed to quantify the expression of target proteins in HNPCs. Luciferase reporter gene assay was applied to detect the effects of E2 and forkhead box O-3 (FOXO3) on matrix metalloproteinases (MMP)-3 promoter activity. Chromatin immunoprecipitation assay analyzed the binding of FOXO3 to MMP-3 and the effect of E2 on this process. RESULTS: We identified the upregulation of collagen II and aggrecan by E2 independent of time and concentration. And E2 downregulated MMP-3 expression in human nucleus pulposus cells. The phosphorylation of FOXO3 led to the reduction of MMP-3 promoter activity. Furthermore, 17ß-estradiol-induced the activation of PI3K/Akt pathway is required for FOXO3 phosphorylated. CONCLUSION: E2 prevents the degradation of ECM by upregulating collagen II and aggrecan expression via reducing MMP-3 expression in HNPCs, and PI3K/Akt/FOXO3 pathway is dispensable for MMP-3 downregulated. Therefore, E2 protects against IDD by preventing ECM degradation. LEVEL OF EVIDENCE: 3.

13.
J Mol Neurosci ; 70(3): 422-432, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31732924

RESUMO

Delayed neurologic sequelae (DNS) are among the most serious complications of carbon monoxide (CO) poisoning caused partly by elevated neuroinflammation. WIN 55,212-2, a non-selective agonist of cannabinoid receptors, has been demonstrated to have anti-inflammatory properties in various brain disorders. The anti-inflammatory action of WIN 55,212-2 is potentially associated with driving microglial M2 polarization. ST2 signaling is important in regulating inflammatory responses and microglial polarization. Therefore, we aimed to investigate the neuroprotective effect of WIN 55,212-2 on DNS after CO poisoning and elucidate its relationship with ST2-mediated microglial M2 polarization. The behavioral tests showed that treatment with WIN 55,212-2 significantly ameliorates the cognitive impairment induced by CO poisoning. This behavioral improvement was accompanied by reduced neuron loss, decreased production of pro-inflammatory cytokines, and a limited number of microglia in the hippocampus. Moreover, WIN 55,212-2 elevated the protein expression of IL-33 (the ligand of ST2) and ST2, increased the ratio of CD206-positive (M2 phenotype) and ST2-positive microglia, and augmented production of M2 microglia-associated cytokines in the hippocampus of CO-exposed rats. Furthermore, we observed that the WIN 55,212-2-mediated increases in ST2 protein expression, CD206-positive and ST2-positive microglia, and microglia-associated cytokines were blocked by the cannabinoid receptor 2 (CB2R) antagonist AM630 but not by the cannabinoid receptor 1 (CB1R) antagonist AM251. In contrast, the WIN 55,212-2-induced upregulation of the IL-33 protein expression was inhibited by AM251 but not by AM630. Altogether, these findings reveal cannabinoid receptors as promising therapeutic agents for CO poisoning and identify ST2 signaling-related microglial M2 polarization as a new mechanism of cannabinoid-induced neuroprotection.

14.
Virus Res ; 275: 197754, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31622636

RESUMO

Herpesvirus infection usually relies on the interaction between viral protein and host protein to enhance replication of the enveloped virus. Fish Carassius auratus herpesvirus (CaHV) is highly pathogenic pathogen causing gill acute hemorrhages of crucian carp (Carassius auratus) and high moritality rates among those infected fish. The protein of CaHV (CaHV-138 L) containing two transmembrane (TM) domains and an immunoglobulin C-2 Type (IGc2) domain was predicted as a viral membrane protein. In this investigation, fluorescence observation showed that full-length CaHV-138 L mainly localized on the plasma membrane or around nuclear membrane of fish fathead minnow (FHM) cells in a punctate pattern. The TM domain deletion mutants of CaHV-138 L (ΔTM1, ΔTM2, and ΔTM1&ΔTM2) diffusely distributed in both the cytoplasm and the nucleus, mainly presented patchy fashion in the cytoplasm, and mainly presented both in the nucleus and in the cytoplasm, respectively. Obviously, the TM domain deletion mutants significantly affected CaHV-138 L subcellular localization. Meanwhile, colocalization assay showed that the full-length viral protein colocalized with mitochondria. Furthermore, the interaction between CaHV-138 L and host protein was identified by yeast two-hybrid (Y2H) and co-immunoprecipitation (co-IP) assays. The host mitochondrial protein FoF1 ATP synthase (FoF1-ATPase) that interacts with this viral protein was screened. The data indicated that CaHV-138 L can target to mitochondrial protein FoF1-ATPase, which might provide energy for virus replication through mediating mitochondrial ATP synthesis. This study has provided valuable information for better understanding of the links of herpesvirus proteins with aquaculture animal proteins.

15.
Ying Yong Sheng Tai Xue Bao ; 30(11): 3903-3910, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31833704

RESUMO

Nematodes, occupying multiple trophic levels in the food web, play important roles in energy flow and nutrient cycling. Most of Chinese natural grasslands have been degraded due to long-term unreasonable utilization, such as over-grazing. External nutrient input is an important way to restore the ecological function of degraded grasslands. The main and intertative effects of nitrogen and phosphorus inputs on soil nematode abundance, trophic group composition and community structure were studied in the grasslands in Xilingol League of Inner Mongolia. Totally, 38 genera of nematodes were recorded. Tylencholaimus, Aphelenchoides, Thonus, and Scutylenchus were dominant genera in this degraded grassland. Nitrogen input decreased total abundances of soil nematodes, and that of omnivores-carnivorous nematodes and plant-feeding nematodes. Phosphorus input increased total abundances of soil nematodes, and that of fungal-feeding nematodes, omnivores-carnivorous nematodes, and plant-feeding nematodes. Nitrogen input inhibited the positive effects of phosphorus input on the abundances of total nematodes, omnivores-carnivorous nematodes and plant-feeding nematodes. Nutrient inputs had no effect on nematode diversity, which would be resulted from the stable plant community. Nitrogen input significantly increased nematode maturity index, decreased plant parasitic nematode maturity index (PPI), and greatly alleviated the negative effects of phosphorus input on PPI and Wasilewska index, indicating that nitrogen input could improve soil health condition and the stability of nematodes community. Our results would help improve our understanding of the effects of nutrient inputs on degraded grassland ecosystem from a soil biotic perspective.


Assuntos
Nematoides , Solo , Animais , China , Ecossistema , Pradaria , Nitrogênio , Fósforo
16.
ACS Appl Mater Interfaces ; 11(50): 46947-46952, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31752484

RESUMO

Hybrid core-shell catalysts possess superior physiochemical properties that are closely related to their atomic structures. Here, we report novel diffusion phenomena in an Au-Ni2P yolk-shell structure using in situ heating transmission electron microscopy (TEM) analysis. The Au yolks can dissolve completely into and diffuse across the Ni2P shell at 500 °C, resulting in an inward volume expansion of the Ni2P shell and shrinkage of the void. The dissolved Au is subsequently segregated, forming a new crystal on the outer layer of the shell. A detailed atomic-scale resolution imaging revealed that the outward Au diffusion and aggregation occur when the Au yolks are epitaxial to the Ni2P shells. Theoretical analysis shows that the outward diffusion and deposition of Au atoms is primarily driven by the excess epitaxial strain energy.

17.
J Phys Chem Lett ; 10(22): 7100-7106, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31682127

RESUMO

The underlying hole-transfer mechanism in high-efficiency OSC bulk heterojunctions based on acceptor-donor-acceptor (A-D-A) nonfullerene acceptors (NFAs) remains unclear. Herein, we study the hole-transfer process between copolymer donor J91 and five A-D-A NFAs with different highest occupied molecular orbital energy offsets (ΔEH) (0.05-0.42 eV) via ultrafast optical spectroscopies. Transient absorption spectra reveal a rapid hole-transfer rate with small ΔEH, suggesting that a large energy offset is not required to overcome the exciton binding energy. Capacitance-frequency spectra and time-resolved photoluminescence spectra confirm the delocalization of an A-D-A-structured acceptor exciton with weak binding energy. Relative to the hole-transfer rate, hole-transfer efficiency is the key factor affecting device performance. We propose that holes primarily stem from weakly bound acceptor exciton dissociation, revealing a new insight into the hole-transfer process in A-D-A NFA-based OSCs.

18.
Biosci Rep ; 39(11)2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31696219

RESUMO

PURPOSE: In the degenerated intervertebral disc (IVD), matrix acidity challenges transplanted bone marrow mesenchymal stem cells (BMSCs). The Ca2+-permeable acid-sensing ion channel 1a (ASIC1a) is responsible for acidosis-mediated tissue injury. The aim of our study was to confirm whether ASIC1a activation induces BMSC apoptosis under conditions that mimic the acidic microenvironment of the degenerated IVD. METHODS: ASIC1a expression in rat BMSCs was investigated by real time-PCR, Western blot (WB) and immunofluorescence. The proliferation and apoptosis of BMSCs under acidic conditions were analyzed by MTT and TUNEL assays. Ca2+-imaging was used to assess the acid-induced increase in the intracellular Ca2+ concentration ([Ca2+]i). The activation of calpain and calcineurin was analyzed using specific kits, and WB analysis was performed to detect apoptosis-related proteins. Ultrastructural changes in BMSCs were observed using transmission electron microscopy (TEM). RESULTS: Acid exposure led to the activation of ASIC1a and increased BMSC apoptosis. The Ca2+ imaging assay showed a significant increase in the [Ca2+]i in response to a solution at pH 6.0. However, BMSC apoptosis and [Ca2+]i elevation were alleviated in the presence of an ASIC1a inhibitor. Moreover, ASIC1a mediated the Ca2+ influx-induced activation of calpain and calcineurin in BMSCs. WB analysis and TEM revealed mitochondrial apoptosis, which was inhibited by an ASIC1a inhibitor, in BMSCs under acidic conditions. CONCLUSIONS: The mimical acidic microenvironment of the degenerated IVD can induce BMSC apoptosis by activating Ca2+-permeable ASIC1a. An acid-induced elevation of [Ca2+]i in BMSCs leads to the subsequent activation of calpain and calcineurin, further resulting in increased mitochondrial permeability and mitochondrial-mediated apoptosis.

19.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(4): 293-296, 2019 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-31701708

RESUMO

OBJECTIVE: To investigate the effects of vitamin E on the respiratory function impairment in rats with chronic obstructive pulmonary disease (COPD) after exposed to high temperature and PM2.5. METHODS: Fifty-four 7-week-old SPF male Wistar rats were randomly divided into 9 experimental groups (n=6). The rat COPD model was established by lipopolysaccharide (LPS) and smoke exposure. After modeled, the rats were tracheal instilled with PM2.5 (0 mg/ml, 3.2 mg/ml) and intraperitoneally injected with vitamin E at the dose of 40 mg/kg (20 mg/ml). Part of rats (high temperature groups) were then exposed to high temperature (40℃), once (8 h) a day for three consecutive days. After the last exposure, the lung function of rats was detected. The expression levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1) were detected by corresponding ELISA kits. RESULTS: Compared with the control group, exposure of high temperature and PM2.5 could inhibit the lung function of COPD rats significantly (P<0.05); the level of MCP-1 was increased significantly in PM2.5-exposure groups (P<0.05); iNOS was increased significantly in the groups of high temperature (P<0.05). Compared with the single-PM2.5 exposure groups, TNF-α in lung was decreased in the normal temperature health group and high temperature COPD group (P<0.05) after treated with vitamin E; MCP-1 was decreased in all vitamin E-treated groups (P<0.05); the decreased iNOS only appeared in the group of high temperature with vitamin E treatment. CONCLUSION: High temperature and PM2.5 could aggravate the inflammation of COPD rats. As an antioxidant, vitamin E may protect the lung from the damage effects.


Assuntos
Temperatura Alta/efeitos adversos , Material Particulado/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Vitamina E/farmacologia , Animais , Quimiocina CCL2/metabolismo , Pulmão/fisiopatologia , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo
20.
J Mater Chem B ; 7(46): 7415-7427, 2019 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-31710069

RESUMO

Although titanium implants have been applied in dental clinics to replace lost teeth and to restore masticatory function for decades, strategies to design the surface of the transmucosal sites of implants to achieve ideal and predictable biological sealing following implantation remain to be optimized. In this study, we hypothesized that gingival epithelial cell (GEC) adhesion and new tissue attachment to titanium sheets/implants could be promoted by the release of plasmid pLAMA3-CM (encoding a motif of the C-terminal globular domain of LAMA3) from a titanium surface. To test this hypothesis, a chitosan/collagen (Chi/Col) coating was immobilized on the surfaces of titanium substrates with nanotube topography (NT-Ti) through cathodic electrophoretic deposition; it was found that pLAMA3-CM could be released from the coating in a highly sustained manner. After culturing on titanium with nanotube topography coated by Chi/Col with the plasmid pLAMA3-CM (Chi/Col/pLAMA3-CM-Ti), human GECs (hGECs) were found to effectively uptake the incorporated plasmids, which resulted in improved attachment, as evidenced by morphological and immunofluorescence analyses. In addition, Chi/Col/pLAMA3-CM-Ti induced better biological sealing at transmucosal sites following immediate implantation into Sprague-Dawley rats. Our findings indicate that the modification of titanium implants by plasmid-mediated pLAMA3-CM gene transfection points to a practical strategy for optimizing biological sealing around the transmucosal sites of implants.

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