SUMMARY OBJECTIVE Diabetes is a risk factor for acute kidney injury (AKI). However, its mechanism of pathogenesis has not been elucidated. The aim of the study was to investigate the role of inflammation and the toll-like receptor 7 (TLR7) in ischemic AKI for diabetes. METHODS A high glucose hypoxia-reoxygenation model of human renal tubular epithelial (HK-2) cells was used to generate AKI induced by ischemia-reperfusion in diabetes. The activity of cells was measured by CCK-8 assay and LDH activity. Inflammatory cytokines were assessed by ELISA. TLR7, MyD88, and NF-κB expressions were examined by western blotting. Apoptosis was evaluated by flow cytometry. RESULTS The high glucose group and low glucose group were subjected to hypoxia-reoxygenation. The low glucose group developed only mild cell damage, apoptosis, and inflammatory response. In contrast, an equivalent hypoxia-reoxygenation injury provoked severe cell damage, apoptosis, and inflammatory response in the high glucose group. Expression of TLR7 and its related proteins were measured in the high glucose group before and after hypoxia-reoxygenation. The high glucose group exhibited more significant increases in TLR7 expression following hypoxia-reoxygenation than the low glucose group. In addition, the expression of TLR7 and its related proteins after hypoxia-reoxygenation were higher in the high glucose group than in the low glucose group. Inhibition of TLR7 provides significant protection against ischemic injury in diabetes. CONCLUSION Our results suggest that diabetes increases the vulnerability to ischemia-induced renal injury. This increased vulnerability originates from a heightened inflammatory response involving the TLR7 signal transduction pathway.
RESUMO OBJETIVO O diabetes é um fator de risco para a lesão renal aguda (LRA). No entanto, seu mecanismo de patogênese não foi elucidado. O objetivo do estudo foi investigar o papel da inflamação e do receptor Toll-like 7 (TLR7) na LRA isquêmica no diabetes. MÉTODOS Um modelo de hipóxia-reoxigenação de células epiteliais tubulares renais humanas (HK-2) na presença de concentrações altas de glicose foi utilizado para gerar LRA induzida por isquemia-reperfusão em diabetes. A atividade das células foi medida pelo ensaio Cell Counting Kit-8 (CCK-8) e pela atividade da lactato desidrogenase (LDH). As citocinas inflamatórias foram avaliadas por ensaio imunoenzimático (Elisa). A expressão de TLR7, do fator de diferenciação mieloide 88 (MyD88) e do fator de transcrição nuclear-κB (NF-κB) foi examinada por Western blotting. A apoptose foi avaliada por citometria de fluxo. RESULTADOS Os grupos glicose alta e glicose baixa foram submetidos à hipóxia-reoxigenação. O grupo de baixa glicose desenvolveu apenas danos celulares ligeiros, apoptose e uma resposta inflamatória. Em contraste, no grupo de alta glicose, uma lesão equivalente de hipóxia-reoxigenação provocou danos celulares graves, apoptose e uma resposta inflamatória. A expressão de TLR7 e suas proteínas relacionadas foi medida no grupo de alta glicose antes e após a hipóxia-reoxigenação. O grupo de alta glicose exibiu maiores aumentos na expressão de TLR7 após hipóxia-reoxigenação do que o grupo de baixa glicose. Além disso, a expressão de TLR7 e suas proteínas relacionadas após a hipóxia-reoxigenação foi maior no grupo com alto nível de glicose do que no grupo com baixo nível de glicose. A inibição do TLR7 fornece proteção significativa contra a lesão isquêmica no diabetes. CONCLUSÃO Nossos resultados sugerem que o diabetes aumenta a vulnerabilidade à lesão renal induzida por isquemia. Essa vulnerabilidade acrescida tem por origem uma resposta inflamatória aumentada envolvendo a via de transdução de sinal do TLR7.
Abstract Purpose: To investigate the prognostic value of 17 platelet-based prognostic scores in patients with malignant hepatic tumors after TACE therapy. Methods: In total, 92 patients were divided into death group and survival group according to long-term follow-up results. The AUC was calculated to determine the optimal cut-off values for predicting prognosis. To determine better prognostic models, platelet-based models were analyzed separately after being showed as binary according to cut-off values. Cumulative survival rates of malignant hepatic tumors were calculated using Kaplan-Meier curves and differences were analyzed by the log-rank test. Univariate and multivariate analyses were performed to identify platelet-based prognostic scores associated with overall survival. Results: Univariate analysis showed that APGA, APRI, FIB-4, FibroQ, GUCI, King's score, Lok index, PAPAS, cirrhosis, number of tumors, vascular cancer embolus, AFP, ALP and APTT were significantly related to prognosis. A multivariate analysis showed that the APGA, number of tumors, ALP and APTT were independently associated with overall survival. Conclusion: This study showed that the APGA, a platelet-based prognostic score, was an independent marker of prognosis in patients with malignant hepatic tumors after TACE and was superior to the other platelet-based prognostic scores in terms of prognostic ability.
ABSTRACT This study aimed to investigate the expression and mechanism of N- methyl -D- aspartate receptor 1 (NMDAR1) in the pathogenesis of Alzheimer disease (AD). Eighty adult Wistar rats were randomly divided into 4 groups (n=20 each) to receive an injection of 0, 5, 7 and 10 μl of 1 μg/μl amyloid-β 42 (Aβ1-42) in the hippocampus. Twenty rats in normal control group were injected with equal volume of saline. After 10 days, the hippocampus was isolated from 5 randomly selected rats in each group. The NMDAR1 protein and mRNA expression was determined by immunohistochemical staining and qRT-PCR. The aquaporin-1 (AQP-1) mRNA expression was also measured by qRT-PCR. We found that both NMDAR1 and AQP-1 expression in Aβ1-42 groups was increased in a dose-dependent manner. NMDAR1 and AQP-1 expression in 7 and 10 μl Aβ1-42 groups was significantly higher compared with 0 μl Aβ1-42 group (P <0.01). Further, the 10 μl Aβ1-42 group was randomly divided into 3 subgroups: AD-NMDA, AD-MK-801, and AD-Ctrl subgroup, which was given an intraperitoneal injection of NMDAR agonist NMDA, NMDAR antagonist MK-801 and saline, respectively. The relative APQ-1 expression in each subgroup was determined by qRT-PCR and Western blot analysis after 24 h. The AQP-1 expression was significantly decreased in AD-MK-801 group (P < 0.05), but was markedly increased in AD-NMDA group when compared with AD-Ctrl group (P <0.01). Our study suggested that expression abnormity of NMDAR1 is involved in the pathogenesis of AD. NMDAR1 might regulate the pathogenic process through stimulating the expression of AQP-1.
ABSTRACT Purpose To investigate whether intracavernosal injection of short hairpin RNA for IGFBP-3 could improve erectile function in streptozotocin-induced diabetic rats. Materials and methods After 12 weeks of IGFBP-3 short hairpin RNA injection treatment, intracavernous pressure responses to electrical stimulation of cavernous nerves were evaluated. The expression of IGFBP-3 and IGF-1 at mRNA and protein levels were detected by quantitative real-time PCR analysis and Western blot, respectively. The concentration of cavernous cyclic guanosine monophosphate was detected by enzyme-linked immunosorbent assay. Results At 12 weeks after intracavernous administration of IGFBP-3 shRNA, the cavernosal pressure was significantly increased in response to the cavernous nerves stimulation compared to the diabetic group (P<0.05). Cavernous IGFBP-3 expression at both mRNA and protein levels was significantly inhibited. At the same time, cavernous IGF-1 expression was significantly increased in the IGFBP-3 shRNA treatment group compared to the diabetic group (P<0.01). Cavernous cyclic guanosine monophosphate concentration was significantly increased in the IGFBP-3 shRNA treatment group compared to the diabetic group (P<0.01). Conclusions Gene transfer of IGFBP-3 shRNA could improve erectile function via the restoration of cavernous IGF-1 bioavailability and an increase of cavernous cGMP concentration in the pathogenesis of erectile dysfunction in streptozotocin-induced diabetic rats.
OBJECTIVE: The aim of this study was to determine the efficacy of 252Californium neutron intracavitary brachytherapy using a two-channel Y applicator combined with external beam radiotherapy for the treatment of endometrial cancer. METHODS: Thirty-one patients with stage I-III endometrial cancer were recruited for this study. The stage I patients received only 252Californium neutron intracavitary brachytherapy with a two-channel applicator. The stage II and III patients received both 252Californium neutron intracavitary brachytherapy using a two-channel applicator and parallel-opposed whole pelvic radiotherapy. RESULTS: The five-year local control rate was 80.6% (25/31), the overall survival rate was 51.6% (16/31), and the disease-free survival rate was 54.8% (17/31). The incidence of serious late complications was 12.9% (4/31). CONCLUSIONS: 252Californium neutron intracavitary brachytherapy using a two-channel applicator combined with external beam radiotherapy was effective for treating endometrial cancer and the incidence of serious late complications related to this combination was within an acceptable range.
The effect of Nb microalloying on structure and physical properties of quenched and tempered 13%Cr martensitic stainless steel was investigated. Excellent strength and adequate toughness properties were obtained by 0.10 wt% Nb addition to low interstitial (N 0.01wt%, C < 0.02wt%) steel. The effect of Nb in 13%Cr steels with high N content was also studied in a commercial martensitic stainless steel sample containing higher levels of N and also alloyed with V. The microstructure, precipitate morphology and dispersion and volume fraction of reverse austenite were characterized. The strength properties obtained in the steel with 0.10%Nb are significantly higher than those of the V-containing steel. The study shows that whereas amount, size and dispersion of precipitates of microalloying elements contribute to enhanced strength, the optimum volume fraction of reverse austenite formed contributes to enhanced ductility and toughness properties. More importantly, high Nb additions to low N -13%Cr-1%Mo steel are found to improve significantly resistance against pitting corrosion significantly.
O efeito da adição de Nb, na microestrutura e nas propriedades mecânicas e de resistência à corrosão dos aços martensíticos com 13% Cr, foi investigado. Excelente resistência mecânica final e suficiente tenacidade e alongamento foram obtidos em aços contendo baixo teor de elementos intersticiais (0.01%N e C < 0.02%) e com adição de 0.10%Nb. O efeito do Nb, também, foi estudado em uma amostra industrial contendo maiores teores de N e adição de V. As propriedades mecânicas obtidas, no aço contendo 0.10% Nb, mostraram-se, significativamente, maiores que aquelas obtidas com o aço contendo V e maior teor de N. A microestrutura, morfologia e dispersão de precipitados, bem como a fração volumétrica de austenita revertida, foram, também, caracterizadas. O tamanho e a dispersão dos precipitados formados a partir dos elementos microligantes contribuem para aumentar a resistência mecânica, enquanto a formação de austenita revertida auxilia na obtenção de tenacidade e ductilidade. Quanto à resistência à corrosão por pite, o desempenho do aço 13Cr5Ni1Mo com maior teor de Nb e menor quantidade de N foi, surpreendentemente, melhor em comparação ao desempenho das demais composições estudadas.