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Ischemia-reperfusion (I/R), a leading risk factor of acute kidney injury (AKI), is associated with high mortality and risk of progression to chronic kidney disease. However, the molecular mechanism of I/R-AKI remains not fully understood, which hinders its efficient clinical treatment. In this study, we observed that LIGHT deficiency remarkably attenuated I/R-AKI, as evidenced by rescued renal function, ameliorated tubular cell apoptosis, and alleviated inflammatory responses. Consistently, blocking LIGHT signaling with its soluble receptor fusion proteins (HVEM-IgG-Fc or LTßR-IgG-Fc) improved I/R renal dysfunction. RNA-sequencing and corresponding results indicated that LIGHT promoted oxidative stress and inflammation triggered by ischemic injury. Moreover, LIGHT signaling augmented ischemic stress-induced mitochondrial dysfunction characterized by an imbalance in mitochondrial fission and fusion, decreased mtDNA copies, impaired mitophagy, and increased mitochondrial membrane potential (ΔΨm). Mechanistically, LIGHT promoted mitochondrial fission by enhancing Drp1 phosphorylation (Ser616) and its translocation to the mitochondria. In conclusion, these results suggest that LIGHT-HVEM/LTßR signaling is critical for the I/R-AKI pathogenesis and it is further confirmed to be related to the increase in I/R-induced oxidative stress and mitochondria dysfunction, which may be the underlying mechanism of LIGHT signaling-mediated I/R-AKI.
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Complement component 3 (C3), a pivotal molecule in the complement system, is an essential immune mediator in various diseases, including psoriasis. However, the mechanistic role of C3 in psoriasis pathology and development remains elusive. Here, we showed that C3 deficiency dramatically augmented imiquimod-induced psoriasis-like skin inflammation, characterized by greater epidermal hyperplasia, inflammatory cell infiltration, and inflammatory gene expression than those in wild-type counterparts. In addition, C3 deficiency promoted imiquimod-induced skin cell apoptosis and supported greater proportions of IFN-γ+ T cells in the inflamed tissues. Accordingly, C3 supplement in the C3 deficient mice reduced skin inflammation and cells apoptosis. Moreover, blocking apoptosis with Z-VAD-FMK, a broad caspase inhibitor, markedly attenuated imiquimod-induced psoriasis-like skin inflammation and IFN-γ+ T cell responses in C3-deficient mice. Collectively, our results suggest that C3 prevents imiquimod-induced psoriasis-like skin inflammation by inhibiting apoptosis.
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Complemento C3/inmunología , Psoriasis/inmunología , Animales , Apoptosis , Complemento C3/análisis , Complemento C3/genética , Citocinas/inmunología , Femenino , Imiquimod , Inflamación/inducido químicamente , Inflamación/inmunología , Inflamación/patología , Interleucina-17/inmunología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Psoriasis/inducido químicamente , Psoriasis/patología , Piel/inmunología , Piel/patología , Linfocitos T/inmunologíaRESUMEN
BACKGROUND: The purpose of this study was to evaluate the prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium and Ureaplasma urealyticum infections in infertile men that consulted our outpatient departments using a novel simultaneous amplification testing (SAT) that is RNA-detection based. The possible impact of C. trachomatis, N. gonorrhoeae, M. genitalium and U. urealyticum infections on semen parameters was also noted in the present study. METHODS: A total of 2607 males that were diagnosed with infertility were included in this study. C. trachomatis, N. gonorrhoeae, M. genitalium and U. urealyticum infections were detected in the urine samples using SAT method. Related data, including semen parameters and age as well as C. trachomatis, N. gonorrhoeae, M. genitalium and U. urealyticum infections were collected and analyzed. RESULTS: A total of 51 and 1418 urine samples were found positive for M. genitalium RNA and U. urealyticum RNA, respectively, while the prevalence of C. trachomatis and N. gonorrhoeae was relatively lower. Men with positive M. genitalium RNA and U. urealyticum RNA had higher sperm DNA fragmentation index (DFI) while the comparisons of other semen parameters yielded nonsignificant results between the RNA positive and negative group. A multivariate linear regression analysis revealed that U. urealyticum and M. genitalium infections posed significant factors of DFI (adjusted R2 = 46.2%). CONCLUSIONS: Our study suggested a relative high prevalence of U. urealyticum and M. genitalium infection based on this novel SAT detection method. U. urealyticum and M. genitalium infection could possibly impair male fertility potential through promoting sperm DNA damage.
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Chlamydia trachomatis/aislamiento & purificación , Infertilidad Masculina/microbiología , Mycoplasma genitalium/aislamiento & purificación , Neisseria gonorrhoeae/aislamiento & purificación , Técnicas de Amplificación de Ácido Nucleico/métodos , Ureaplasma urealyticum/aislamiento & purificación , Adulto , China/epidemiología , Chlamydia trachomatis/genética , Humanos , Infertilidad Masculina/epidemiología , Masculino , Mycoplasma genitalium/genética , Neisseria gonorrhoeae/genética , Prevalencia , ARN Bacteriano/genética , Ureaplasma urealyticum/genética , Orina/microbiología , Adulto JovenRESUMEN
Objective· To establish an integrative method for the gene-panel sequencing data to automatically complete quality control, detection of gene mutation and visualization. Methods · Integrate several methods, e.g. FastQC, preprocessing and information of sequences (Prinseq) to develop an R package that can be used to visualize and control the quality of the raw sequencing reads and final mutations result. The sequencing reads mapped against to the reference genome using Burrows-Wheeler Alignment Tool (BWA)/Torrent Mapping Alignment Program (TMAP). Lofreq, Varscan2, the Genome Analysis Toolkit (GATK) and Torrent Variant Caller (TVC) were used to detect gene mutation and get the variant call format (VCF) format file. Annotate the gene mutation sites using Annovar. Results · Thirty-six cases of acute myeloid leukemia sequencing from Ion Torrent Personal Genome Machine (PGM) platform were passed by this analysis tool.Ten mutation sites of 2 demo data were found in DNMT3A,TET2,JAK2,PHF6,ASXL1,NPM1 and CEBPA which were validated by sanger sequencing. Conclusion · The analysis method that integrated and developed several tools for gene-panel sequencing data analysis can accomplish the gene-panel sequencing data analysis effectively. Besides, it can reduce the false positive ratio and improve the sensitivity of gene mutation detection that provides support for the analysis of gene-panel sequencing data.
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Objective: To explore the relationship between the incidences of percutaneous coronary intervention (PCI) complicated depression and serum levels of brain-derived neurotrophic factor (BDNF), ghrelin in coronary artery disease (CAD) patients. Methods: A total of 90 CAD patients after PCI were enrolled. According to Hamilton depression (HAMD) scale, the patients were divided into 2 groups: Depression group, n=40 and Non-depression group, n=50. Serum levels of BDNF and Ghrelin were examined by ELISA and compared between 2 groups. Results: Compared with Non-depression group, Depression group had reduced serum levels of BDNF and Ghrelin, both P<0.05. As increased severity of depression, BDNF and Ghrelin were decreased accordingly; serum levels of BDNF and Ghrelin were negatively related to HAMD score (r=-0.711, P<0.05 and r=-0.711, P<0.05). Conclusion: Serum levels of BDNF and Ghrelin have an early warning effect on depression in CAD patients after PCI, it may reflect the severity of depression at certain degree in relevant patients.
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OBJECTIVE: To study the neurophysiologic of detrusor overactivity (DO) due to partial bladder outflow obstruction (PBOO). METHODS: Twenty four female Wistar rats with DO caused by PBOO were studied simultaneously with ten sham-operated rats. An electrophysiological multi-channel simultaneous recording system was used to record pelvic afferent fiber potentials as well as the pudendal nerve motor branch potentials, external urethral sphincter electromyogram (EUS EMG) and abdominal muscle EMG during filling cystometry. To test the effect of the unstable contraction in DO rats after the decentralization of the central nervous system, DO rats were studied the changes of the unstable contraction after transection of the spinal cord (T(8) level), pelvic nerve, the sympathetic trunk, and the pudendal nerve. RESULTS: The incidence of DO was 62.5% in filling cystometry. During filling cystometry, there are two type of DO contraction according to the changes of pelvic afferent fiber signals, the relevant nerves and muscles responses: the small pressure of the unstable contraction (S-DO) and the big pressure of the unstable contraction (B-DO). For the B-DO, there were significant changes in the recordings of pelvic afferent fiber, the motor branch of the pudendal nerve, EUS EMG, and abdominal muscle EMG. While all these differences have not been recorded during S-DO. Both the filling-voiding cycle and the unstable contraction of B-DO were eliminated and the base line of bladder pressure increased after T(8) spinal cord transection. While the S-DO was not affected by such transection. When bladder relevant nerves were transected by the sequence of the pelvic nerve, the sympathetic trunk, and the pudendal nerve, the filling-voiding cycle was eliminated. The base line of bladder pressure increased significantly. No B-DO was recorded, but the S-DO still existed. CONCLUSION: There are some bladder-genic factors take part in the DO contractions induced by PBOO.
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Obstrucción del Cuello de la Vejiga Urinaria/fisiopatología , Vejiga Urinaria Hiperactiva/fisiopatología , Animales , Modelos Animales de Enfermedad , Femenino , Diafragma Pélvico/inervación , Ratas , Ratas Wistar , Vejiga Urinaria/inervación , Obstrucción del Cuello de la Vejiga Urinaria/complicaciones , Vejiga Urinaria Hiperactiva/etiologíaRESUMEN
OBJECTIVE: To investigate the role of ICC-like cells in bladder neuromodulation in rat urinary bladder. METHODS: 14 SD rats and 1 guinea pig were sacrificed in this study. The ultra structural relationships among interstitial cells, nerves and detrusor smooth muscle cells (DSMCs) of urinary bladder were investigated by transmission electron microscopy (TEM). c-kit immunofluorescence was used to identify ICC-like cells in SD rat urinary bladder and the structural relationship between ICC-like cells and nerve terminals was studied by immunofluorescence (double-label). RESULTS: Gap junction between ICC-like cells and DSMCs was confirmed by TEM. ICC-like cells were very close apposition with nerve terminals under TEM. ICC-like cells were identified to exist in sub-urothelium layer, along the longitude of smooth muscle bundles and among detrusor smooth muscle in SD rat urinary bladder by c-kit immunofluorescence. Double-labeled tissue with c-kit and PGP9.5 antibodies also showed that ICC-like cells were very close apposition with nerve terminals in SD rat bladder. CONCLUSIONS: Morphological study indicated that ICC-like cells in rat urinary bladder may play an important role in detrusor neuromodulation. Further study on function will be helpful for elucidating the mechanism of bladder neuromodulation clearly.