Effect of H2S on the expression of p38MAPK and caspase3 and apoptosis in renal tissue of urogenous sepsis / 医学研究生学报

ObjectiveTo study the mechanism of renal injury in urogenic sepsis and explore the effect of H2S on the expression of p38 mitogen-activated protein kinase (p38MAPK) and Cysteine protease 3(Caspase3) and apoptosis in renal tissue of urogenic sepsis. Hydrogen sulfide (H2S) has a wide range of biological effects and has a certain protective effect on the kidney. The main objective of this study is to investigate the effect of H2S on the expression of p38 mitogen-activated protein kinase (p38MAPK), cysteine proteinase 3 (Caspase3), and cell apoptosis in renal tissue of urogenic sepsis, and further to study the mechanism of urinary sepsis renal injury.MethodsNew Zealand rabbits (n=40) were divided into five groups Control, Sham, Sepsis, NaHS, and PAG, with eight rabbits in each group. The vital signs, blood routine white blood cell count, neutrophil count, and renal function (Cr, BUN) of five groups of New Zealand rabbits were recorded before the operation, 24 hrs after the operation, 48 hrs after the operation, and 72 hrs after the operation. 72 hrs after the operation, the left kidney tissue was taken for HE staining to observe the changes of cell morphology and structure of the kidney tissue. The apoptotic cells in renal tissue were labeled by Tunel assay (in situ terminal transferase labeling technique). The expression levels of p38MAPK and Caspase3 in renal tissue were tested by ELISA.Results The apoptosis indexes of renal tissue cells in group Control and group Sham were (5.65±2.43)% and (5.57±2.72)%, respectively, with no statistically significant difference (P>0.05). The apoptosis index of rabbit kidney tissue in group Sepsis was (25.26±2.70)%, which was significantly higher than that in group Control and group Sham (P0.05). Pairwise comparison between groups Sepsis, NaHS, and PAG showed statistically significant differences (P<0.05). The expression levels of group Sepsis and group PAG were significantly higher than that of group NaHS (P<0.05). The expression level of group PAG was significantly higher than that of group Sepsis (P<0.05).Conclusion H2S can alleviate renal damage caused by urine-derived sepsis, and its mechanism combined with H2S to suppress the expression of p38MAPK and Caspase3 in the renal tissue of urogenous sepsis, thereby reducing renal cell apoptosis Death.

Hydrogen sulfide attenuates urosepsis-induced acute kidney injury by blocking TLR4/MyD88/PI3K signaling pathway / 中国病理生理杂志

AIM:To explore the effect of hydrogen sulfide (H2S) on urosepsis-induced acute kidney injury.METHODS:New Zealand white rabbits were randomly divided into control group, sham group, model (sepsis) group, Na HS treatment (Na HS) group, and Na HS combined with TAK-242 (a TLR4 inhibitor) treatment (Na HS+TAK-242) group.After treatment for 72 h, HE staining was used to measure the histopathological changes of rabbit kidney.The levels of blood urea nitrogen (BUN) and serum creatinine (SCr) were detected by automatic biochemical analyzer.The serum levels of neutrophil gelatinase-associated lipocalin (NGAL) , kidney injury molecule 1 (KIM-1) , procalcitonin (PCT) , interleukin-1β (IL-1β) , interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by ELISA.The TLR4/MyD88/PI3K signaling pathway-related proteins in the kidney were determined by Western blot.RESULTS:Compared with control group, obvious damage was observed in the kidneys of septic rabbits, but the kidneys were markedly improved by treatment with Na HS.The levels of BUN, SCr, NGAL, KIM-1, PCT, IL-1β, IL-6 and TNF-αin the septic rabbits were higher than those in control group, and decreased significantly in Na HS group and Na HS+TAK-242 group.The protein levels of TLR4, MyD88, p-PI3K and p-Akt in septic rabbit kidneys were higher than those in control group.However, Na HS or Na HS+TAK-242 inhibited the activation of TLR4/MyD88/PI3K signaling pathway in the kidneys of septic rabbits.CONCLUSION:H2S play a protective effect on the rabbits with urosepsis-induced acute kidney injury by blocking TLR4/MyD88/PI3K signaling pathway to inhibit inflammatory response.

NLRP3, a Double-edged Sword in Lung Injury Diseases.

Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) plays a key role in lung injury diseases regulation, and its expression is increased in lung injury diseases. NLRP3 may be a good therapeutic target for lung injury diseases. The molecular mechanisms of NLRP3 in lung injury diseases remain unclear. It is a key to study the potential mechanism of NLRP3 during lung injury diseases, so that to exploit it as a good target for lung injury diseases therapy.

Extralobar pulmonary sequestration in a 55-year-old man.

Pulmonary sequestration is a rare congenital lung malformation that more commonly occurs in the left lung, mainly near the lower mediastinum. It is rarely observed in patients with extralobar sequestration in adulthood. We report the case of a 55-year-old man with recurrent fever and cough lasting for about 1 month, who was admitted to our hospital. His past history was unremarkable. The final diagnosis of extralobar sequestration was dependent on three-dimensional computed tomography angiography (3D CTA), which showed an abnormal blood supply vessel to the consolidation from the aortic arch. The patient underwent a left pulmonary sequestration resection, and the pathological examination also verified the diagnosis postoperatively. 3D CTA images can provide an aberrant vessel anatomy map for the surgeon and play a decisive role in the detection of pulmonary sequestration.

Role of microRNAs in atrial fibrillation: new insights and perspectives.

MicroRNAs (miRNAs) are small non-coding RNA molecules that negatively regulate gene expression of their targets at the post-transcriptional levels. They typically affect the mRNA stability or translation finally leading to the repression of target gene expression. Notably, it is thought that miRNAs are crucial for regulating gene expression during heart diseases, such as atrial fibrillation (AF). Numerous studies identify specific miRNA expression profiles associated to different histological features of AF, both in animal models and in patients. Therefore, we review the latest experimental approaches from the perspective of understanding miRNA gene expression regulatory networks in AF. In addition, miRNAs have also emerged as possible therapeutic targets for the treatment of AF. In this review, we discuss the experimental evidence about miRNAs both as potential non-invasive early diagnostic markers and as novel therapeutic targets in AF.

Pulmonary lobectomy on delayed inhaled foreign body in adult: a case report.

We present the case of a 51 years old female who experienced foreign body aspiration 3 years before. The foreign body, which should be removed by bronchoscopy before, was lodged at the bifurcation of the right inferior bronchus and could only be removed via right lower lobectomy. The patient experienced a swift recovery and was well at follow-up 8 months later.

Evolution of tricuspid regurgitation after mitral valve surgery for patients with moderate-or-less functional tricuspid regurgitation.

OBJECTIVES: The purpose of this study was to evaluate the impact of moderate-or-less functional tricuspid regurgitation (TR) treatment on the clinical outcome of patients with mitral valve (MV) surgery. METHODS: From October 2001 to January 2005, 167 patients in our hospital with MV surgery and without organic tricuspid valve (TV) disease or pulmonary hypertension (PH) showed moderate-or-less functional TR preoperatively, and 41.9% of these patients were treated with TR (group T), compared with 58.1% untreated with TR (group no-T). According to tricuspid annulus dimension (TAD)/body surface area (BSA), these 167 patients were further divided into another 2 groups (A and B): group A (70 patients) represented TAD/BSA ≤ 21 mm/m2 with 32 patients from group T and 38 from group no-T, and group B (97 patients) represented TAD/BSA > 21 mm/m2 with 38 patients from group T and 59 patients from group no-T. There was no statistical difference in preoperative and operative variables between the 2 groups. Meanwhile, among the 167 patients with MV surgery, 157 patients were replaced with MV and 10 patients were repaired with MV, and De Vega technique was constantly used for TR treatment. All the results were estimated by multivariate analysis. RESULTS: The median follow-up time was 63 months (25th and 75th percentiles are 53 and 94 months, respectively); 30-day mortality was 3% (1.4% in group T versus 4.1% in group no-T; P = .31). Adjusted 5-year survival was 70.7% (66.6%-80.4%) with 85.3% (83.0%-93.4%) in group T and 64.7% (33.7%-58.3%) in group no-T, P = .001. Among the 70 patients with TAD/BSA ≤ 21 mm/m2, patients who received treatment of moderate-or-less TR and those who did not showed similar secondary TR grade at postoperative period (0.5 ± 0.6 in group T versus 0.9 ± 0.9 in group no-T; P = .2) and follow-up (1.3 ± 1.1 in group T versus 1.8 ± 1.1 in group no-T; P = .06). In subgroup B (TAD/BSA > 21 mm/m2), patients who received tricuspid valvoplasty manifested more significantly improved outcome than patients without functional TR at postoperative period (0.8 ± 0.8 in group T versus 1.6 ± 1.3 in group no-T; P = .03) and follow-up (2.0 ± 1.2 in group T versus 3.0 ± 1.1 in group no-T; P = .005). The multivariate analysis identified TAD/BSA > 21 mm/m2 and preoperative atrial fibrillation (AF) as the risk factors for lower survival at follow-up period. CONCLUSIONS: Patients with MV surgery have better midterm outcome when they receive either more aggressive and effective surgical treatment for functional TR or moderate-or-less TR preoperatively. Indexed TAD (TAD/BSA > 21 mm/m2) is a more reliable surgical guideline for the treatment of TR. Preoperative tricuspid annulus dilation and AF might be predictors of late lower survival.

Recombinant adenovirus-mediated RNA silencing of tissue factor expression in human islet: an in vitro study / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct a replication-incompetent recombinant adenovirus mediating short hairpin RNA (shRNA)-induced tissue factor gene silencing in the islet.</p><p><b>METHODS</b>Four pairs of complementary oligonucleotides were designed and synthesized to create double-stranded oligonucleotides (ds oligo). The ds oligos were cloned into Pentr/U6 vector to construct the shuttle plasmid pENTR/U6-shRNA, which was transduced into human islets via liposome after sequence verification. The plasmid with the best silencing effect was identified by real-time RT-PCR, followed by homologous recombination with the adenovirus backbone plasmid. The functional clone was transfected into 293A cells to amplify the adenovirus, whose silencing effect against TF expression was tested using real-time RT-PCR and Western blotting.</p><p><b>RESULTS</b>The pENTR/U6-shRNA shuttle plasmid was constructed and verified by sequencing. The recombinant adenovirus-mediated shRNA against TF was constructed, and real-time RT-PCR and Western blotting demonstrated that the strongest silencing effect of the adenovirus against TF occurred on the 4th day following islet transfection.</p><p><b>CONCLUSION</b>Replication-incompetent recombinant adenovirus-mediated shRNA against TF has been successfully constructed, which has good silencing effect against TF expression in human islet in vitro.</p>