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1.
Psychogeriatrics ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31951677

RESUMO

BACKGROUND: Postoperative delirium (POD) is a very common complication in elderly patients after hip fracture surgery, which has poorly understood pathophysiology. This study aimed to investigate potential risk factors for POD. METHODS: Elderly patients (aged ≥65 years) scheduled to undergo selective surgery in our hospital were consecutively recruited. Patient characteristics, preoperative laboratory tests and prognostic nutritional index (PNI) levels were compared between patients with or without POD. The risk factors for POD were evaluated by univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive value of PNI and age for POD. RESULTS: Fifty-seven of the 163 enrolled patient had suffered POD within postoperative day 7 with an incidence of 35.0%. Multivariate logistic analyses revealed that an advanced age (cut-off value: 71.5 years, sensitivity: 48.1%, specificity: 75.4%, odds ratio (OR): 3.24, 95% CI: 1.16-8.69, P = 0.026) and lower PNI level (cut-off value: 47.45, sensitivity: 86.0%, specificity: 51.9%, OR: 2.88, 95% CI: 1.25-6.64, P = 0.012) were two independent predictive factors associated with POD. According to the ROC curve analysis, preoperative PNI level was a predictor for POD with an area under the curve of 0.686 (95% CI: 0.604-0.767, P < 0.001). CONCLUSIONS: Advanced age and lower preoperative PNI level were significantly associated with POD in elderly patients after hip fracture surgery.

2.
Oncol Lett ; 18(6): 6180-6186, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31788093

RESUMO

Ultrasound (US) combined with magnetic resonance imaging (MRI) in the diagnosis of primary hepatocellular carcinoma (PHCC) and recurrent hepatocellular carcinoma (RHCC) were compared. The clinical data of 329 patients with hepatocellular carcinoma (HCC) admitted to Qingdao Women and Children's Hospital from June 2015 to December 2017 were collected. One hundred and sixty patients with PHCC were regarded as the PHCC group, and the other 169 patients with RHCC were regarded as the RHCC group. US and MRI were used in the imaging diagnosis of both groups and the results of US combined with MRI, US, and MRI alone were compared. The lesion size in the PHCC group was significantly higher than that in the RHCC group (P<0.05). The MRI fast-in and fast-out rates of the two groups were significantly higher than those of the other three methods (P<0.05). The coincidence rate of MRI in the two groups was higher than that of computed tomography (CT), US, and US combined with MRI (P<0.05). The coincidence rates of CT, US, MRI, and US combined with MRI in PHCC group were significantly higher than those in RHCC group. In PHCC group, MRI was superior to the other methods in the detection of micro HCC (P<0.05). In RHCC group, MRI was significantly better than US in the detection of micro HCC (P<0.05). The sensitivity, specificity, positive predictive value and negative predictive value of MRI were significantly better than the other three methods (P<0.05). MRI alone has the best diagnostic efficacy for micro HCC-type lesions. The diagnostic efficacy of MRI, US, CT, and US combined with MRI in PHCC was better than those in RHCC. In addition to imaging examination, the diagnosis of RHCC should be combined with other indicators for comprehensive diagnosis.

3.
Opt Express ; 27(16): 23250-23261, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31510606

RESUMO

Multi-frequency Terahertz (THz) detectors have shown great application potentials in THz imaging and sensing systems. For the first time to our knowledge, a novel dual-frequency THz detector with the stacked structure consisting of a silicon-based plasmonic antenna and a metal-based antenna in one compact unit is proposed and fabricated in standard CMOS technology. Compared with the metal antenna, the antenna based on heavy-doped poly-silicon materials enables the detector to excite localized surface plasmon resonance mode, making the effective absorption of the THz waves and thus resulting in the significant responsivity enhancement of the detector. The experimental results show a maximum voltage responsivity up to about 2000 V/W and 450 V/W, while the noise equivalence power is as low as 23 pW/Hz0.5 and 110 pW/Hz0.5 for the silicon antenna and metal antenna at the frequency of 220 GHz and 650 GHz, respectively. The presented dual-frequency detector can be easily implemented in a small size in favor of high-density array integration.

4.
Stem Cell Res ; 39: 101511, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31404746

RESUMO

Human breast milk epithelial cells (BMECs) can be isolated and cultured with high purity. Induced pluripotent stem cells (iPSCs) were generated from BMECs with Yamanaka factors (OCT4, SOX2, c-MYC, KLF4) using episomal system. Pluripotency of breast milk-derived iPSCs (BM-iPSCs) was confirmed by the expression of pluripotent markers with immunocytochemistry and spontaneous differentiation of three germ layers in vitro and teratoma formation assay in vivo. Besides, the iPSC lines displayed normal karyotype. Breast milk is a non-invasive and easily accessible cell source, we can obtain BM-iPSCs from BMECs with low costs in a transgene-free episomal system.

6.
Opt Lett ; 44(9): 2197-2200, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31042182

RESUMO

We report on the high-performance nanoporous (NP) GaN-based metal-insulator-semiconductor (MIS) ultraviolet (UV) photodetectors (PDs) with a thermal oxidized ß-Ga2O3insulating layer. The devices show a high responsivity of 4.5×105 A/W and maximum external quantum efficiency of 1.55×108% at 360 nm under a 10 V applied bias, which are attributed to the trap-assisted tunneling induced internal gain mechanism. Correspondingly, a specific detectivity of 8.27×1015 Jones and excellent optical switching repeatability are also observed in our fabricated PDs. The NP-GaN/ß-Ga2O3 MIS UV PD may act as an excellent candidate for the application in UV photodetection due to the high performance and simple fabrication process.

7.
Int J Oncol ; 54(5): 1567-1578, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30896790

RESUMO

Emerging evidence indicates that mesenchymal stem cells (MSCs) serve an indispensable role in the tumor microenvironment. However, whether MSCs participate in the development of oral carcinogenesis remains unclear. The present study isolated MSCs from clinical tissues and investigated the differences of MSCs derived from normal oral mucosa (N­MSC), oral leukoplakia with dysplasia (LK­MSC) and oral carcinoma (Ca­MSC). The results revealed that the LK­MSCs exhibited reduced proliferation and migration, compared with the N­MSCs and Ca­MSCs. Furthermore, it was demonstrated that the exosomes secreted by LK­MSCs have significant roles in promoting proliferation, migration and invasion in vitro, which was similar to the Ca­MSC­derived exosomes. The promoting effect was also demonstrated in a 3D coculture model. When the secretion of exosomes was blocked, the promoting effect of LK­MSCs was reversed. Based on a microarray analysis of MSC­derived exosomes, microRNA­8485 (miR­8485) was identified to be ectopically expressed. The exosomal miR­8485 was capable of promoting the proliferation, migration and invasion of tumor cells. Therefore, the present study highlights the significance of MSC­derived exosomes and exosomal miR­8485 in premalignant lesions and carcinogenesis. Intervention with the secretion of MSC­derived­exosomes may be an innovative strategy to retard the carcinogenesis.


Assuntos
Exossomos/patologia , Leucoplasia Oral/patologia , MicroRNAs/genética , Mucosa Bucal/citologia , Neoplasias Bucais/patologia , Adulto , Idoso , Diferenciação Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Células Cultivadas , Técnicas de Cocultura/métodos , Exossomos/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Leucoplasia Oral/genética , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Neoplasias Bucais/genética , Microambiente Tumoral , Regulação para Cima
9.
Glia ; 67(3): 438-451, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30578562

RESUMO

Emerging evidence indicates that spinal neuroinflammation contributes to the maintenance of chronic inflammatory pain. IL-36, as a novel member of the interleukin (IL)-1 super-family cytokines, plays an important role in inflammatory responses. The present study aimed to investigate the role of spinal IL-36 and IL-36 receptor (IL-36R) signaling in the pathology of chronic inflammatory pain. IL-36γ and IL-36R, but not IL-36α and IL-36ß, were persistently upregulated in the spinal cord of mice with intraplantar injections of complete Freund's adjuvant (CFA). Intrathecal administration of both IL-36R antagonist (IL-36Ra) and IL-36γ siRNA significantly attenuated CFA-induced chronic inflammatory pain behaviors. Furthermore, CFA-induced IL-36γ expression was mainly observed in spinal neurons whereas IL-36R was primarily expressed in spinal astrocytes. Additionally, the intrathecal injection of IL-36γ was sufficient to induce pain hypersensitivity and astrocyte activation in naive mice, and these effects could be inhibited by blocking c-Jun N-terminal kinase (JNK) phosphorylation. In vitro experiments also demonstrated that the IL-36γ could induce astrocytic JNK activation and inflammatory cytokines release, which was mediated by IL-36R. Finally, intrathecal injection of IL-36γ-activated astrocytes in a pJNK-dependent manner induced mechanical allodynia and thermal hyperalgesia in naive mice. Collectively, these findings reveal that the neuronal/astrocytic interaction in the spinal cord by which neuronally produced IL-36γ activates astrocytes via IL-36R-mediated JNK pathway is crucial for the maintenance of chronic inflammatory pain. Thus, IL-36γ/IL-36R-mediated astrocyte signaling may be a suitable therapeutic target for chronic inflammatory pain.


Assuntos
Astrócitos/metabolismo , Inflamação/metabolismo , Interleucina-1/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Dor/metabolismo , Receptores de Interleucina-1/metabolismo , Animais , Astrócitos/efeitos dos fármacos , Modelos Animais de Doenças , Adjuvante de Freund , Hiperalgesia/metabolismo , Inflamação/induzido quimicamente , Interleucinas/farmacologia , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Dor/induzido quimicamente , Medição da Dor , Fosforilação
10.
Artigo em Inglês | MEDLINE | ID: mdl-31921705

RESUMO

Fusobacterium nucleatum is one of the most frequent pathogenic bacteria causing periodontitis. The direct effect of Fusobacterium nucleatum (F. nucleatum) on oral stem cells has rarely been reported. In this study, we aimed to evaluate how gingiva-derived mesenchymal stem cells (GMSCs) respond to a direct challenge with F. nucleatum. GMSCs were isolated by the limiting dilution method and exposed to F. nucleatum at various multiplicities of infection (MOIs; F. nucleatum:cell ratios of 10:1, 50:1, and 100:1) for 24 h to 4 weeks. Our results indicated that F. nucleatum significantly inhibited cell proliferation in a dose-dependent manner and promoted cell migration and the release of chemokines/cytokines, such as CCL2, CXCL1, and IL-6. Additionally, F. nucleatum inhibited GMSC osteogenic differentiation partly by decreasing alkaline phosphatase (ALP) activity, mineralized nodule formation, and osteogenesis-related gene and protein expression. RNA-sequencing analyses indicated that F. nucleatum time-dependently activated cellular signaling pathways during the process of osteogenic differentiation. A total of 64 cell differentiation-related genes were found to be differentially expressed between non-infected and F. nucleatum-infected GMSCs at 3, 7, 14, and 21 d. Intriguingly, we discovered that the 64 cell differentiation-related differentially expressed genes (DEGs) were significantly enriched in cancer-related pathways, such as bone cancer, osteosarcoma and bone marrow cancer, which provides new insight into tumorigenesis during the process of GMSC osteogenic differentiation. In conclusion, this study demonstrates that persistent exposure to F. nucleatum promotes cell migration and chemokine/cytokine release and inhibits the proliferation and osteogenic differentiation of GMSCs. Our study provides a novel and long-time bacteria-cell co-culture in vitro model and makes a foundation for the future mechanistic studies of GMSCs under F. nucleatum infection.

11.
Biopreserv Biobank ; 16(6): 426-433, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30484701

RESUMO

A major concern in biomedical research is the quality of biological samples. RNAlater is a stabilizer, which was originally developed for RNA preservation in fresh tissues and is important for collection and transportation. However, this reagent lacks a comprehensive and systematic evaluation of its preservative effect on different mammalian tissues under consistent experimental conditions. In this study, we collected liver, kidney, testis, brain, and colon tissues from mice and divided the samples into the following respective groups: fresh, RNAlater preserved, and liquid nitrogen snap frozen. Biomolecules (RNA, DNA, and protein) were extracted from each tissue in each group, and samples were formalin fixed and paraffin embedded for quality assessment. Our results revealed that high-quality (yield, purity, and integrity) nucleic acids could be extracted from all samples. Gene expression determined by quantitative real-time polymerase chain reaction exhibited no major difference among the three groups. Notably, we observed significant protein degradation in brain tissue preserved by RNAlater compared with fresh and snap-frozen tissue. Protein expression of the other four tissues was similar among the three groups. Hematoxylin and eosin staining of all tissue types indicated no apparent difference among the three groups. We concluded that high-quality nucleic acids can be obtained and tissue morphology conserved when tissues are preserved with RNAlater. However, there are tissue-specific differences in protein preservation when using RNAlater, which should be evaluated before extensive storage.


Assuntos
Crioprotetores/química , Proteínas/análise , RNA/análise , Fixação de Tecidos/métodos , Preservação de Tecido/métodos , Animais , Criopreservação , DNA/análise , DNA/isolamento & purificação , DNA/metabolismo , Imuno-Histoquímica/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Especificidade de Órgãos , Proteínas/isolamento & purificação , Proteínas/metabolismo , RNA/isolamento & purificação , RNA/metabolismo , Estabilidade de RNA
13.
World J Surg Oncol ; 16(1): 179, 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-30185198

RESUMO

BACKGROUND: To validate the clinical value of simple rules in distinguishing malignant adnexal masses from benign ones and to explore the effect of simple rules for experienced and less-experienced sonographers. METHODS: Patients with persistent adnexal masses were enrolled between November 2013 and December 2015. All masses were proven through histological examinations. Five sets of diagnoses were made and compared with one another. Diagnosis 1 was made, according to the simple rules, by a trainee with little clinical diagnostic experience. Diagnoses 2 and 3 were made by experienced and less-experienced sonographers, respectively, according to their clinical experiences. With diagnosis 1 as a reference, the two sonographers were asked to provide a second diagnosis, which were diagnoses 4 and 5. The efficiency of the five sets of diagnoses was compared using ROC curves. RESULTS: In total, 75 malignant (37.7%) and 124 benign lesions (62.3%) were enrolled in this study. The mean diameter of the benign masses was obviously smaller than that of the malignant ones (6.8 ± 3.4 cm vs. 9.3 ± 4.9 cm, p < 0.01). The malignant ratio in postmenopausal women was much higher (66.1%) than that in the premenopausal population (25.7%) (p < 0.0001). Totally, 156 of the 199 cases (79.4%) resulted in conclusive diagnoses. Sensitivity and specificity were 98.4% and 73.9%, respectively, among the conclusive cases. The area under the ROC curve (Az) for the simple rule diagnosis was significantly lower than that for the experienced sonographer diagnosis (0.85 vs. 0.96, p < 0.0001); compared with the less-experienced sonographer, this difference was not significant (0.85 vs. 0.86, p = 0.9776). No significant difference was found in the comparison between the diagnoses made by the experienced sonographer before and after referencing the simple rule diagnosis (Az, 0.96 vs. 0.97, p = 0.2055). Using diagnosis 1 as a reference, the diagnostic performance of the less-experienced sonographer increased (from 0.86 to 0.92, p = 0.012); however, it was still lower than that of the experienced sonographer (Az, 96% vs. 92%, p = 0.0241). CONCLUSIONS: The simple rules was an appealing method for discriminating malignant masses from benign ones, particularly for a less-experienced sonographer.


Assuntos
Doenças dos Anexos/diagnóstico por imagem , Competência Clínica/normas , Pessoal de Saúde/normas , Ultrassonografia/normas , Doenças dos Anexos/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Curva ROC , Sensibilidade e Especificidade , Adulto Jovem
14.
J Neurooncol ; 140(2): 359-366, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30182160

RESUMO

PROPOSE: To explore the value of unmeasurable enhancement pattern of residual cavity in predicting survival at early stage after gross-total resection in high-grade glioma (HGG) patients. METHODS: This retrospective study enrolled consecutive 51 HGG patients with unmeasurable enhancement who underwent gross-total resection followed by concurrent chemoradiotherapy and adjuvant chemotherapy. We evaluated the enhancement patterns of residual cavity on contrast-T1WI made within 1 month after tumor resection (20 ± 3 days). The survival state of different enhancement was compared. RESULTS: Thin-linear, thick-linear and nodular enhancement were observed in 22 patients (43%), 10 patients (20%), and 19 patients (37%), respectively. The progression-free survival of patients with thin-linear (487, 151-887 days) was longer than those patients with thick-linear (277, 133-573 days), and nodular enhancement (210, 120-765 days) (P = 0.002). The overall survival of patients with thin-linear (774, 457-1343 days) was longer than those with thick-linear (462, 320-678 days), and nodular enhancement (326, 234-1393 days) (P = 0.002). There was no significant difference of orthogonal value between thick-linear and nodular enhancement (0.854), neither between grade III and IV with same enhancement patterns (P = 0.540, P = 0.720). CONCLUSIONS: The unmeasurable enhancement patterns in HGG patients within 1 month after gross-total resection, which might be better than the grade of tumor, holds a potential marker in survival state.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Imagem por Ressonância Magnética , Período Pós-Operatório , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/efeitos da radiação , Encéfalo/cirurgia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Criança , Terapia Combinada , Feminino , Seguimentos , Glioma/mortalidade , Glioma/patologia , Glioma/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Procedimentos Neurocirúrgicos , Prognóstico , Estudos Retrospectivos , Adulto Jovem
15.
Opt Express ; 26(12): 15308-15315, 2018 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-30114780

RESUMO

In this paper, deep level transient spectroscopy (DLTS) characterization was performed on Beryllium compensation doping of InGaAs/GaAsSb type-II superlattice photodiode. Three electron traps with the energy levels located at Ec-0.11 eV (E1), Ec-0.28 eV (E2), Ec-0.17 eV (E3), and a hole trap situated at Ev + 0.25 eV (H1) were revealed. The position distribution and depth concentration of these traps in SL absorption region was also explored. Furthermore, the bandlike states (E2) and localized states (E1 and H1) of extended defects were confirmed by DLTS measurements as a function of the filling-pulse time, these traps as generation-recombination centers are responsible for dominant dark current.

16.
Nanoscale ; 10(29): 14368, 2018 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-29999093

RESUMO

Correction for 'Metabolomic profiles delineate the potential role of glycine in gold nanorod-induced disruption of mitochondria and blood-testis barrier factors in TM-4 cells' by Bo Xu et al., Nanoscale, 2014, 6, 8265-8273.

17.
Biomed Pharmacother ; 105: 151-158, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29852392

RESUMO

Mesenchymal stem cells (MSCs) have been used clinically and experimentally to relieve severe immune-related diseases due to their immunomodulatory properties, but these are impaired by inflammation. Oral lichen planus (OLP) is a T cell-mediated chronic inflammatory mucosal disease. In the present study, we found MSCs from OLP with higher expression of interleukin (IL)-6, tumour necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-ß) and IL-10 compared with control. Total glucosides of paeony (TGP) significantly improves the immunomodulatory function of MSCs by inhibiting IL-6 and TNF-α expression and increasing TGF-ß and IL-10 expression. Moreover, TGP can downregulate p-STAT3 expression through upregulation of miR-124. The changes of IL-6, TGF-ß and p-STAT3 were further confirmed by overexpression and knockdown of miR-124 in MSCs. Taken together, the immune-regulating function of MSCs can be improved by TGP via the miR-124/STAT3 pathway.


Assuntos
Glucosídeos/uso terapêutico , Imunomodulação/efeitos dos fármacos , Líquen Plano Bucal/tratamento farmacológico , Células-Tronco Mesenquimais/efeitos dos fármacos , MicroRNAs/metabolismo , Paeonia/química , Fator de Transcrição STAT3/metabolismo , Adulto , Células Cultivadas , Citocinas/genética , Citocinas/imunologia , Feminino , Glucosídeos/isolamento & purificação , Humanos , Líquen Plano Bucal/imunologia , Líquen Plano Bucal/metabolismo , Masculino , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , Transdução de Sinais
18.
J Appl Toxicol ; 38(8): 1091-1103, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29578247

RESUMO

The mechanism of male reproductive toxicity induced by benzo[a]pyrene (BaP) is poorly understood. Gap junctional intercellular communication (GJIC) is known to play a critical role in maintaining spermatogenesis. The aim of the present study was to determine the toxic effects of BaP in Sertoli cells, and to explore the possibility and potential mechanisms of BaP-induced changes in the level of GJIC, and the relationship between GJIC and BaP-induced apoptosis. We treated mouse Sertoli cell lines (TM4) with different concentrations (0.1-100 µm) of BaP for 1-48 hours, and found that GJIC exhibited a dose- and time-dependent downregulation. Treatment with 10 µm BaP increased apoptosis, intracellular Ca2+ level ([Ca2+ ]i ) and calmodulin (CaM) protein expression, and decreased the protein level of connexin 43 (Cx43) (also known as gap junction α-1 protein [GJA1]) in TM4 cells. However, BaP had no effect on the phosphorylation of Cx43 at Ser279/282, Ser255, Ser368 or Ser262. Downregulation of [Ca2+ ]i by BAPTA-AM significantly attenuated the BaP-induced GJIC suppression, Cx43 protein decrease and CaM protein increase. Interestingly, inhibition of CaM expression by W7 partially recovered BaP-induced GJIC inhibition, but had no effect on BaP-induced Cx43 protein decrease. Pretreatment with the GJIC activator retinoic acid significantly mitigated BaP-induced apoptosis. In conclusion, these results suggest that BaP can decrease GJIC via Ca2+ /CaM signaling, and that BaP-induced GJIC suppression increases apoptosis in TM4 cells.


Assuntos
Apoptose/efeitos dos fármacos , Benzo(a)pireno/toxicidade , Comunicação Celular/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Junções Comunicantes/efeitos dos fármacos , Células de Sertoli/efeitos dos fármacos , Animais , Cálcio/metabolismo , Calmodulina/metabolismo , Técnicas de Cultura de Células , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Junções Comunicantes/metabolismo , Masculino , Camundongos , Células de Sertoli/metabolismo
19.
Toxicol Lett ; 288: 35-43, 2018 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-29444456

RESUMO

Cadmium (Cd), a toxic heavy metal, is known to induce renal toxicity by primarily targeting at renal proximal tubule. Endoplasmic reticulum (ER) stress and gap junctional intercellular communication (GJIC) regulate many pathophysiological processes. Yet, how ER stress and GJIC regulate Cd-induced nephrotoxicity remain elusive. In this study, we treated human proximal tubule (HK-2) cells with 1 µM CdCl2 every other day for 12 days and found that Cd significantly increased cell apoptosis at 10 and 12 days. This cytotoxicity correlated with activation of ER stress and apoptotic signaling evidenced by upregulation of inositol-requiring enzyme 1 (IRE1α), splice X-box binding protein-1 (XBP-1s), and apoptosis signal-regulating kinase 1 (ASK1) proteins. Interestingly, the AKT signaling was activated at 2- and 4-day and then inhibited at 10- and 12-day of Cd treatment; by contrast, Cd decreased GJIC levels at 2- and 4-day followed by a significant increase at 10- and 12-day treatment. Activation of AKT by SC79 or inhibition of GJIC by 18α-glycyrrhetinic acid (18α-GA) completely abolished Cd-induced AKT inhibition and IRE1α-ASK1 activation. Importantly, pretreatment with ER stress inhibitor or 18α-GA significantly mitigated Cd-induced apoptosis. These results suggest that GJIC collaborates with AKT signaling and ER stress in regulating prolonged Cd-treatment-induced apoptosis in HK-2 cells.


Assuntos
Apoptose/efeitos dos fármacos , Cloreto de Cádmio/toxicidade , Comunicação Celular/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Junções Comunicantes/efeitos dos fármacos , Cloreto de Cádmio/antagonistas & inibidores , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Espaço Extracelular , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Túbulos Renais Proximais/citologia , Túbulos Renais Proximais/efeitos dos fármacos , Proteína Oncogênica v-akt , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
20.
Stem Cells Int ; 2017: 4378947, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29250119

RESUMO

Stem cell research provides promising strategies in improving healthcare for human beings. As a noninvasively obtained and easy-to-culture cell resource with relatively low expense, urine-derived stem cells have special advantages. They have been extensively studied on its proliferation ability and differentiation potential and were being reprogrammed to model diseases during the last decade. In this review, we intend to summarize the latest progress on the research of urine-derived stem cells for its broad application mainly in regenerative medicine and disease modeling, as well as in what is challenging currently. This minireview will highlight the potential application of urine-derived stem cells and provides possible direction of further research in the future.

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