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1.
J Affect Disord ; 260: 670-679, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31550613

RESUMO

BACKGROUND: It has been suggested that mother-infant psychotherapy may offer an alternative approach to treating postpartum depression, but little is known about its effectiveness. This review presents a summarized effectiveness of mother-infant psychotherapy on postpartum depression. METHODS: Multiple electronic databases were searched including Pubmed, Cochrane Library, EMBase, MEDLINE, et al. Hand searching of references was also performed. Randomized controlled trials reporting on mother-infant psychotherapy targeting postpartum depression were included if they used a validated measure of prescribing appropriateness. Evidence quality was assessed using the Cochrane risk of bias tool. RESULTS: A total of 13 randomized controlled trials met inclusion criteria and were included in the final analysis. In the short-term effect analysis, mother-infant psychotherapy reduced standardized mean depressive scores (-0.25, 95% CI -0.40, -0.09) and risk ratio (0.71, 95% CI 0.55, 0.91). In the long-term effect analysis, mother-infant psychotherapy did not improve maternal mood, mother-infant interaction and infant attachment. LIMITATIONS: Clinical heterogeneity was observed among included studies in mother-infant psychotherapy intervention, suggesting the existence of potential moderators such as intensity, frequency, trimester of pregnancy or type of mother-infant psychotherapy. CONCLUSION: Mother-infant psychotherapy appears to be effective for the treatment of maternal depression in the short-term. Future studies with better design/execution and larger sample size are needed to confirm the effect of mother-infant psychotherapy on short-term and to explore its effect on long-term depression.

2.
Chemosphere ; 238: 124637, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31470312

RESUMO

The addition of powdered activated carbon (PAC) to remove micropollutants is a commonly used technology to improve drinking water quality. However, the effects of PAC dosing strategy on the coagulation-flocculation process of water treatment have not been well understood, especially for water with low amounts of inorganic particles. Therefore, the current research aimed to comprehensively study the effects of simultaneous addition of PAC and aluminum sulfate (AS) coagulants (denoted as PAC-AS) or adding PAC 2 h before coagulation (denoted as PAC2h-AS) on the coagulation behavior in humic acid (HA) and HA-kaolin water treatment. The results showed that the floc size, growth rate, breakage factor, and fractal dimension were all enhanced by PAC-AS and PAC2h-AS for HA but not for HA-kaolin water treatment. In HA water treatment, PAC-AS reached a larger floc size and faster growth rate, while PAC2h-AS achieved a larger floc breakage factor and fractal dimension value. For PAC2h-AS, the pre-adsorption of HA onto PAC would lower the initial particle concentration and reduce the collision probability during HA water coagulation process; thus, the DOC removal efficiency, floc size, and growth rate of PAC2h-AS were relatively smaller than those of PAC-AS. For the floc strength and floc fractal dimension, the pre-adsorption of HA onto PAC contributed to formation of stronger inter-particle bonds; thus, stronger and more compact flocs were formed by PAC2h-AS compared with those of PAC-AS. The addition of PAC had a smaller impact on the floc properties in HA-kaolin water treatment owing to its higher initial particle concentration.

3.
Ann Hum Genet ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674661

RESUMO

OBJECTIVE: The aim of this study was to investigate pathogenic variants and molecular etiologies of Stargardt disease (STGD) in a cohort of Chinese families. MATERIALS AND METHODS: A cohort of 12 unrelated STGD families diagnosed on the basis of clinical manifestations underwent analysis by targeted exome or whole-exome sequencing. Bioinformatics analysis, Sanger sequencing, and cosegregation analysis of available family members were used to validate sequencing data and confirm the presence of disease-causing genes. RESULTS: Using targeted exome and whole-exome sequencing, we found that eight families had disease-causing variants in the ABCA4 gene, one family had only one heterozygous variant in the ABCA4 gene, and the remaining three families have not been identified with any disease-causing variants for STGD. We identified 15 variants in the ABCA4 gene; of these, five variants have not been previously described for STGD. CONCLUSION: The findings in this study expand the data regarding the frequency and spectrum of variants in the ABCA4 gene, thus potentially enriching our understanding of the molecular basis of STGD. Moreover, they constitute clues for future STGD diagnosis and therapy.

4.
Scand J Gastroenterol ; : 1-9, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31686555

RESUMO

Objective: To investigate the clinical value of the adjuvant transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) after radical resection, and identify the potential beneficiaries.Methods: Patients were identified through the primary liver cancer big data (PLCBD) between 2012 and 2015. Overall survival (OS) between adjuvant TACE group and non-TACE was evaluated by Kaplan-Meier before and after propensity scoring match (PSM). Subgroup analysis was conducted stratified by risk factors.Results: A total of 2066 HCC patients receiving radical resection were identified. Patients with multiple tumors, tumor diameter >5 cm, satellite, and advanced stage were more likely to accept adjuvant TACE. Before PSM, the 1-, 3-, and 5-year OS rates in the TACE group and non-TACE group were 89%, 58%, 17%, and 88%, 53%, 13% (p = .43), respectively. While, the corresponding rates were 89%, 58%, 17%, and 86%, 49%, 11%, (p = .038), respectively after 1:1 PSM. In addition, patients were found to significantly benefit from adjuvant TACE if they had age ≥50 years, no cirrhosis, AFP ≤ 200 ng/ml, surgical margin <1 cm, tumor diameter >5 cm, no capsule, no satellite, or CN stage Ib/IIa (all p < .05), but patients with age < 50 years, tumor size ≤5 cm, or CN stage Ia were found to significantly benefit from radical resection in DFS (all p < .05).Conclusion: Currently, we concluded that not all of patients with HCC would benefit from adjuvant TACE. Patients with age ≥50 years, tumor size >5 cm, or CN stage Ib/IIa were strongly recommended to receive adjuvant TACE.

5.
ISA Trans ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31690455

RESUMO

This paper considers a reliable cooperative control and plug-and-play operation problem in networked heterogeneous systems (NHSs), and focuses on the scenario subjected to physical attack-induced actuator failures/uncertainties and Denial-of-Service (DoS) attacks on communication channels between physical nodes. To solve it, a new self-feedback control with an adaptive integral sliding-mode compensator is developed. The new one configures each heterogeneous system under the malicious actuator failures/uncertainties to be passivity-short (PS). The PS index quantifies the impact of each attacked heterogeneous dynamics on their networked operations. Furthermore, based on cloud networks, a novel network-level distributed control is proposed. It improves robustness of the systems against DoS with no frequency and duration constraints. And then, a technical condition is presented with the aid of the impact equivalence principle. Under the condition, the self-feedback and network-level controls designed separately but performed together ensure the leader-follower consensus and plug-and-play operation of the attacked NHSs. Finally, the effectiveness of the proposed method is verified by flight control systems.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31698072

RESUMO

Two lipopolysaccharides (LPS) and ß-1, 3-glucan binding protein (LGBP), designated as PcLGBP isoform1 and PcLGBP isoform2, respectively, were identified from Procambarus clarkii in this study. The full-length cDNA of PcLGBP isoform1 was 1308 bp containing an open reading frame (ORF) of 1113 bp encoding a protein of 370 amino acids. The full-length cDNA of PcLGBP isoform2 was 1440 bp containing an ORF of 1245 bp encoding a protein of 414 amino acids. Predicted PcLGBP isoform1 and PcLGBP isoform 2 proteins contained a signal peptide, a glycoside hydrolase domain, and a low-complexity region. The difference between the two LGBP isoforms was that PcLGBP isoform2 had 44 more amino acids behind the signal peptide than the PcLGBP isoform1. The PcLGBP isoform1 and PcLGBP isoform2 transcripts mainly expressed in the hepatopancreas in female and male crayfish. Moreover, the expression levels of the two genes in the hepatopancreas were higher in male than that in female crayfish. Upon being challenged with Vibrio parahaemolyticus or LPS, the expression levels of PcLGBP isoform1 and PcLGBP isoform2 in the hepatopancreas of female and male crayfish were most significantly up-regulated at different time points. The transcripts of anti-lipopolysaccharide factors (ALF5, ALF6, ALF8, and ALF9) and crustins (CRU1, CRU2, CRU3, and CRU4) were evidently down-regulated in the hepatopancreas of V. parahaemolyticus-challenged total PcLGBP (including PcLGBP isoform1 and PcLGBP isoform2)-silenced male crayfish. In addition, the phenoloxidase (PO) activity in the hepatopancreas of male crayfish was evidently higher than that of female crayfish. PcLGBP knock down could significantly decrease the PO activity in the hepatopancreas lysate (HLS) in male crayfish. The PO activity of male crayfish HLS was significantly increased when incubated with a mixture of recombinant LGBP protein and LPS or ß-1, 3 glucan. We conclude that LGBP isoforms from P. clarkii function as a pattern recognition protein for recognizing and binding LPS and ß-1, 3 glucan, and thus regulate the synthesis of antimicrobial peptides and activate the prophenoloxidase system.

8.
Med Sci Monit ; 25: 7557-7566, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31592001

RESUMO

BACKGROUND Owing to the increased incidence of photodermatosis caused by ultraviolet light in recent years, it is necessary to clarify the mechanisms potential photodamage to the skin and reveal possible therapeutic targets. Heat shock protein 27 (Hsp27) is well known for suppressing apoptosis. The aim of present study was to elucidate possible photoprotective mechanism between Hsp27 and p21 on ultraviolet B (UVB)-induced photodamage. MATERIAL AND METHODS The Hsp27 gene was interfered to assess the expression of its downstream effectors, cell apoptosis, and cell proliferation ability. The cell apoptosis was tested using flow cytometry method. The cell proliferation ability was tested using Cell Counting Kit-8 (CCK-8) assay. The expression of protein was tested using western-blotting method. The expression of mRNA was detected using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The subcellular localization was elucidated using immunofluorescence. RESULTS Hsp27 knockdown decreased cell viability and increased the incidence of UVB-induced apoptosis. Compared with control group, activation of phosphorylated-Akt (p-Akt)-dependent pathway resulted in the nuclear accumulation of p21 and suppression of cell proliferation, while promoting apoptosis in Hsp27 knockdown group. In addition, Hsp27 knockdown increased p53 expression and the Bax: Bcl-2 ratio, which further accelerated the apoptotic process. CONCLUSIONS These findings complemented the mechanism of skin photodamage and demonstrated the photoprotective mechanisms of Hsp27 in HaCaT cells, which might implicate a potential therapeutic target of photodamage and photodermatosis.

9.
Cancer Biol Ther ; : 1-11, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31663424

RESUMO

Tumor-associated macrophages (TAMs), which generally exhibit an M2-like phenotype, play a critical role in tumor development. Triptolide exerts a unique bioactive spectrum of anticancer activities. The aim of this study was to determine whether triptolide has any effect on the activation of TAMs and the production of tumor-promoting mediators. ICR-1 mice with azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colon tumors and BALB/c mice co-inoculated with 4T1 cells and M2-polarized RAW264.7 cells were used to examine whether the inhibitory effect of triptolide on tumor progression was mediated by the targeting of TAMs. Real-time PCR, Western blot, immunofluorescence staining, and flow cytometry assays were performed to determine the expression of cell surface markers and cytokine production. The results showed that triptolide inhibited macrophage differentiation toward the M2 phenotype and abolished M2 macrophage-mediated tumor progression. Furthermore, triptolide inhibited the expression of M2 markers, such as CD206, Arginase 1, and CD204, and inhibited the secretion of anti-inflammatory cytokines. Thus our study indicated that triptolide selectively inhibited the functions of M2-polarized macrophages and TAMs, and this inhibitory effect of triptolide on TAM viability, differentiation, and cytokine production might elucidate the major mechanisms underlying its antitumor activity. Our findings provide important information for the potential clinical application of triptolide in cancer therapy.

10.
EBioMedicine ; 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31636010

RESUMO

BACKGROUND: Diabetic retinopathy, a vascular complication of diabetes mellitus, is the leading cause of visual impairment and blindness. circRNAs act as competing endogenous RNA, sponging target miRNA and thus influencing mRNA expression in vascular diseases. We investigated whether and how circDNMT3B is involved in retinal vascular dysfunction under diabetic conditions. METHODS: qRT-PCR was performed to detect expression of circDNMT3B, miR-20b-5p, and BAMBI in retinal microvascular endothelial cells under diabetic conditions. Western blot, Cell Counting Kit-8, Transwell, Matrigel tube formation, and retinal trypsin digestion assays were conducted to explore the roles of circDNMT3B/miR-20b-5p/BAMBI in retinal vascular dysfunction. Bioinformatics analysis and luciferase reporter, siRNA, and overexpression assays were used to reveal the mechanisms of the circDNMT3B/miR-20b-5p/BAMBI interaction. Electroretinograms were used to evaluate visual function. FINDINGS: Upregulation of miR-20b-5p under diabetic conditions promoted proliferation, migration, and tube formation of human retinal microvascular endothelial cells (HRMECs), which was mediated by downregulated BAMBI. Under diabetic conditions, circDNMT3B, which acts as a sponge of miR-20b-5p, is downregulated. circDNMT3B overexpression reduced retinal acellular capillary number and alleviated visual damage in diabetic rats. Changes in expression of circDNMT3B and miR-20b-5p were confirmed in the proliferative fibrovascular membranes of patients with diabetic retinopathy. INTERPRETATION: Downregulation of circDNMT3B contributes to vascular dysfunction in diabetic retinas through regulating miR-20b-5p and BAMBI, providing a potential treatment strategy for diabetic retinopathy. FUNDING: National Natural Science Foundation of China, National Key Basic Research Program of China, Shanghai Municipal Science and Technology Major Project, and ZJLab.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31612643

RESUMO

AIM: Immune suppression based on alternative regulation of immune checkpoint proteins, for example, programmed cell death receptor-1 (PD-1) and cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), which results in T-cell exhaustion, contributes to cancer development and progression. In this study, we sought to characterize the distribution of CTLA-4 and T-cell lymphocyte activation gene-3 (LAG-3) expression on exhausted T cells in different T-cell subsets from patients with acute myeloid leukemia (AML). METHODS: The coexpression of CTLA-4 and LAG-3 on exhausted CD244+ and CD57+ T cells from the CD3+ , CD4+ , and CD8+ T-cell subsets in peripheral blood from 12 patients with newly diagnosed AML was analyzed by multicolor flow cytometry assay. RESULTS: A significantly higher percentage of CTLA-4+ CD3+ , CD4+ and CD8+ T cells was found in patients with AML. In addition, higher numbers of both CTLA-4+ CD244+ and CTLA-4+ CD57+ CD3+ T cells were detected. Interestingly, the increased CTLA-4+ CD244+ T cells were predominantly CD4+ T cells. In contrast, the increased CTLA-4+ CD57+ T cells primarily consisted of the CD8+ T-cell subset. A high proportion of LAG-3+ T cells was found in only a few cases with AML; however, a significantly higher proportion of coexpression of CTLA-4 and LAG-3 in the CD3+ and CD8+ T-cell subsets was detected. CONCLUSION: We for the first time observed higher CTLA-4+ CD244+ CD4+ , CTLA-4+ CD57+ CD8+ , CTLA-4+ LAG-3+ CD3+ and CTLA-4+ LAG-3+ CD8+ T cells in patients with AML, whereas the upregulated expression of LAG-3 on T cells was only found in a subset of the cases. These data may provide further information by complementing the heterogeneity of immune checkpoints expression in AML.

12.
Fish Shellfish Immunol ; 94: 792-799, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31585244

RESUMO

The caspase is an essential module in the Drosophila immune deficiency (IMD) pathway, which plays a crucial role in countering pathogen infection. In this study, a gene named PcCaspase-3C was found in Procambarus clarkia with a full-length of 4684 bp, including a 1572 bp opening reading frame, which encoded a putative protein of 523 amino acids. PcCaspase-3C contained a CASc domain constituted of 237 amino acids. The PcCaspase-3C gene was primarily expressed in heart, stomach, and intestine, while less in gonad, hepatopancreas, gills, and hemocytes, with the least expression in muscle. Infection with Staphyloccocus aureus, Vibrio parahaemolyticus or white spot syndrome virus (WSSV) induced an up-regulated expression of PcCaspase-3C in intestine or stomach to varying degrees. When PcCaspase-3C was silenced by double-stranded RNA, the expression of some antimicrobial peptides such as ALF2, ALF5, ALF6, Cru3, Cru4, and Lys was significantly inhibited. In addition, silencing of PcCaspase-3C accelerated infection with WSSV in vivo. According to these results, we suggest that PcCaspase-3C might play a crucial role in the immune response of P. clarkia against pathogenic bacterial and viral infections.

13.
J Cell Biochem ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31642106

RESUMO

Circular RNAs (circRNAs) have been extensively studied in many tumors. The aim of this study was to demonstrate the relationship between circRNAs and clinical features, prognosis, and diagnosis of osteosarcoma patients. We mainly included studies about circRNAs expression and osteosarcoma. The odds ratio (ORs) and 95% confidence intervals (CIs) were used for clinical features, sensitivity, and specificity, while the hazard ratios (HRs) and 95% CIs were used to assess overall survival (OS). A number of 13 articles were included in this study, including 9 about clinical features, 11 about prognosis, and 5 about diagnosis. The results showed that increased circRNAs expression was significantly correlated with adverse clinical characteristics. In terms of prognosis, oncogenic circRNAs had adverse effects on overall survival (OS: HR = 2.54; 95%Cl: 2.05-3.03), and increased expression of cancer-suppressor circRNAs prolonged survival (OS: HR = 0.42; 95%Cl: 0.210.64). Our study further showed an AUC of 0.85, with an 80% sensitivity and 77% specificity to distinguish osteosarcoma patients from healthy controls. In conclusion, circRNAs may be new promising indicators for prognostic evaluation and early diagnosis of osteosarcoma patients.

14.
J Vis Exp ; (152)2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31657793

RESUMO

Primaquine (PMQ), an important anti-malarial drug, has been recommended by the World Health Organization (WHO) for the treatment of life-threatening infections caused by P. vivax and ovale. However, PMQ has unwanted adverse effects that lead to acute hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. There is a need to develop simple and reliable methods for PMQ determination with the purpose of dosage monitoring. In early 2019, we have reported an UV-Vis and naked-eye based approach for PMQ colorimetric quantification. The detection was based on a Griess-like reaction between PMQ and anilines, which can generate colored azo products. The detection limit for direct measurement of PMQ in synthetic urine is in the nanomolar range. Moreover, this method has shown great potential for PMQ quantification from human serum samples at clinically relevant concentrations. In this protocol, we will describe the technical details regarding the syntheses and characterization of colored azo products, the reagent preparation, and the procedures for PMQ determination.

15.
Oncogene ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31597953

RESUMO

The development of chemoresistance remains a major challenge that accounts for colorectal cancer (CRC) lethality. Dichloroacetate (DCA) was originally used as a metabolic regulator in the treatment of metabolic diseases; here, DCA was assayed to identify the mechanisms underlying the chemoresistance of CRC. We found that DCA markedly enhanced chemosensitivity of CRC cells to fluorouracil (5-FU), and reduced the colony formation due to high levels of apoptosis. Using the microarray assay, we noted that miR-149-3p was involved in the chemoresistance of CRC, which was modulated by wild-type p53 after DCA treatment. In addition, PDK2 was identified as a direct target of miR-149-3p. Mechanistic analyses showed that overexpression of miR-149-3p enhanced 5-FU-induced apoptosis and reduced glucose metabolism, similar to the effects of PDK2 knockdown. In addition, overexpression of PDK2 partially reversed the inhibitory effect of miR-149-3p on glucose metabolism. Finally, both DCA treatment and miR-149-3p overexpression in 5-FU-resistant CRC cells were found to markedly sensitize the chemotherapeutic effect of 5-FU in vivo, and this effect was also validated in a small retrospective cohort of CRC patients. Taken together, we determined that the p53/miR-149-3p/PDK2 signaling pathway can potentially be targeted with DCA treatment to overcome chemoresistant CRC.

16.
Nanoscale ; 11(39): 18311-18319, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31573008

RESUMO

Despite the excellent room-temperature phosphorescence (RTP) property of carbon dot (CD)-based RTP composites, the development of these emerging materials with finely tunable afterglow lifetimes still remains a challenge. Herein, for the first time, we report a series of pure organic RTP composite materials based on adjustable polyaniline carbon dots (PACDs) and polymer matrices (polyacrylic acid, polyacrylamide, and polyvinyl alcohol) with tunable RTP lifetimes. By using different polymer matrices and adjusting the functional groups of PACDs, the strength of hydrogen bonding between each polymer matrix and PACDs was regulated, and green RTP emissions with a tunable average lifetime ranging from 184 ms to 652 ms were also realized. In addition, taking advantage of their different persistent afterglow lifetimes, naked-eye-observable and time-resolved anti-counterfeit and data encryption patterns were prepared using these PACDs/polymer composites, demonstrating the potential application of these materials.

17.
Haematologica ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601687

RESUMO

Transferrin receptor 1 (Tfr1) mediates the endocytosis of diferric transferrin in order to transport iron, and Tfr1 has been suggested to play an important role in hematopoiesis. To study the role of Tfr1 in hematopoiesis, we generated hematopoietic stem cell (HSC) specific Tfr1 knockout mice (Tfr1-CKO). We found that Tfr1-CKO mice reached full term but died within one week of birth. Further analyses revealed that Tfr1-deficient HSCs had impaired development of all hematopoietic progenitors except thrombocytes and B lymphocytes. In addition, Tfr1-deficient cells had cellular iron deficiency, which blocked the proliferation and differentiation of hematopoietic precursor cells, attenuated the commitment of hematopoietic lineages, and reduced the regeneration potential of HSCs. Notably, hemin rescued the colony-forming capacity of Tfr1-deficient HSCs, whereas expressing a mutant Tfr1 that lack the protein's iron-transporting capacity failed to rescue hematopoiesis. These findings provide direct evidence that Tfr1 is essential for hematopoiesis through binding diferric transferrin to supply iron to cells.

18.
Int Immunopharmacol ; 77: 105959, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31644961

RESUMO

Tripterygium wilfordii Hook. F. (TwHF), a traditional Chinese Medicine, is effective in treating rheumatoid arthritis (RA), but its severe nephrotoxicity limits its extensive application. The nephrotoxic mechanism of Triptolide (TP), the main pharmacological and toxic component of TwHF, has not been fully revealed. This study was designed to explore the nephrotoxicity of TP in the RA state and the potential molecular mechanism. A rat collagen-induced arthritis (CIA) model was constructed and administered with TP for 28 days in vivo. Results showed that the kidney injury induced by TP was aggravated in the CIA state, the concentration of TP in the renal cortex was higher than that of the medulla after TP administration in the CIA rats, and the expression of organic cation transporter 2 (Oct2) in kidney was up-regulated under CIA condition. Besides, rat kidney slice study demonstrated that TP was transported by Oct2 and this was confirmed by transient silencing and overexpression of OCT2 in HEK-293T cells. Furthermore, cytoinflammatory models on HK-2 and HEK-293T cell lines were constructed by exposure of TNF-α or IL-1ß to further explore the TP's renal toxicity. Results suggested that TNF-α exposure aggravated TP's toxicity and up-regulated the protein expression of OCT2 in both cell lines. TNF-α treatment also increased the function of OCT2 and finally OCT2 silencing confirmed OCT2 mediated nephrotoxicity of TP in HEK-293T cells. In summary, the exposure of TNF-α in RA state induced the expression of OCT2, which transported more TP into kidney cortex, subsequently exacerbated the kidney injury.

19.
iScience ; 21: 1-18, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31654850

RESUMO

Aberrant RAS signaling activation is common in cancers with even few Ras mutations, indicating alternative dysregulation other than genetic mutations. We identified a Ras GTPase-activating gene RASA5/SYNGAP1, at the common 6p21.3 deletion, methylated/downregulated in multiple carcinomas and different from other RASA family members (RASA1-RASA4), indicating its special functions in tumorigenesis. RASA5 mutations are rare, unlike other RASA members, whereas its promoter CpG methylation is frequent in multiple cancer cell lines and primary carcinomas and associated with patient's poor survival. RASA5 expression inhibited tumor cell migration/invasion and growth in mouse model, functioning as a tumor suppressor. RASA5 suppressed RAS signaling, depending on its Ras GTPase-activating protein catalytic activity, which could be counteracted by oncogenic HRas Q61L mutant. RASA5 knockdown enhanced Ras signaling to promote tumor cell growth. RASA5 also inhibited epithelial-mesenchymal transition (EMT) through regulating actin reorganization. Thus, epigenetic inactivation of RASA5 contributing to hyperactive RAS signaling is involved in Ras-driven human oncogenesis.

20.
J Cell Mol Med ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31568643

RESUMO

Renal cell carcinoma (RCC) is a heterogeneous histological disease and it is one of the most common kidney cancer. The treatment of RCC has been improved for the past few years, but its mortality still remains high. Chelerythrine (CHE) is a natural benzo[c]phenanthridine alkaloid and a widely used broad-range protein kinase C inhibitor which has anti-cancer effect on various types of human cancer cells. However, its effect on RCC has not been fully elucidated. In this study, we evaluated the effect and mechanism of CHE on RCC cells. Our study showed that CHE induced colony formation inhibition and G2/M cell cycle arrest in a dose-dependent manner in RCC cells. In addition, CHE increased cellular ROS level, leading to endoplasmic reticulum (ER) stress, inactivating STAT3 activities and inducing apoptosis in RCC cells which were suppressed by NAC, a special ROS inhibitor. We further found that both knockdown of ATF4 protein and overexpression of STAT3 protein could reduce CHE-induced apoptosis in Caki cells. These results demonstrated that the apoptosis induced by CHE was mediated by ROS-caused ER stress and STAT3 inactivation. Collectively, our studies provided support for CHE as a potential new therapeutic agent for the management of RCC.

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