Combined detection of urine specific gravity and BK viruria on prediction of BK polyomavirus nephropathy in kidney transplant recipients / 中华医学杂志(英文版)

BACKGROUND@#BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) is an important cause of dysfunction and failure of renal transplants. This study aimed to assess the diagnostic performance of morning urine specific gravity (MUSG) in diagnosing BKPyVAN in kidney transplant recipients.@*METHODS@#A total of 87 patients, including 27 with BKPyVAN, 22 with isolated BKPyV viruria, 18 with T cell-mediated rejection (TCMR), and 20 with stable graft function, were enrolled in the First Affiliated Hospital of Sun Yat-Sen University from March 2015 to February 2017. MUSG at biopsy and during a follow-up period of 24 months after biopsy was collected and analyzed. Receiver operating characteristic (ROC) curve analysis was used to determine the ability of MUSG to discriminate BKPyVAN.@*RESULTS@#At biopsy, the MUSG of BKPyVAN group (1.008 ± 0.003) was significantly lower than that of isolated BK viruria group (1.013 ± 0.004, P < 0.001), TCMR group (1.011 ± 0.003, P = 0.027), and control group (1.014 ± 0.006, P < 0.001). There was no significant difference in MUSG among the isolated BK viruria group, TCMR group, and control group (P = 0.253). In BKPyVAN group, the timing and trend of MUSG elevate were consistent with the timing and trend of the decline of viral load in urine and plasma, reaching a statistical difference at 3 months after treatment (1.012 ± 0.003, P < 0.001) compared with values at diagnosis. ROC analysis indicated that the optimal cut-off value of MUSG for diagnosis of BKPyVAN was 1.009, with an area under the ROC curve (AUC) of 0.803 (95% confidence interval [CI]: 0.721-0.937). For differentiating BKPyVAN and TCMR, the optimal MUSG cut-off value was 1.010, with an AUC of 0.811 (95% CI: 0.687-0.934).@*CONCLUSION@#Combined detection of MUSG and BKPyV viruria is valuable for predicting BKPyVAN and distinguishing BKPyVAN from TCMR in renal transplant recipients.

Prognosis of BK polyomavirus nephropathy: 10-year analysis of 133 renal transplant recipients at a single center / 中华医学杂志(英文版)

BACKGROUND@#BK virus-associated nephropathy (BKVN) is an important cause of chronic allograft dysfunction. The objective of our study was to evaluate the prognosis of BKVN.@*METHODS@#We retrospectively reviewed the data of 133 renal transplant recipients with BKVN treated at the First Affiliated Hospital of Sun Yat-Sen University between July 2007 and July 2017. BK viral loads, graft function, and pathologic indexes were compared between initial diagnosis and last follow-up.@*RESULTS@#After a mean follow-up period of 14.4 (range, 0.3-109.6) months after diagnosis of BKVN, BK viruria, and BK viremia become negative in 19.5% and 90.2% of patients, respectively. The mean estimated glomerular filtration rate (eGFR) at last follow-up was lower than at diagnosis of BKVN (18.3 ± 9.2 vs. 32.8 ± 20.6 mL·min·1.73 m, t = 7.426, P < 0.001). Eight (6.0%) patients developed acute rejection after reducing immunosuppression. At last follow-up, the eGFR was significantly lower in patients with subsequent rejection than those without (21.6 ± 9.8 vs. 33.5 ± 20.9 mL·min·1.73 m, t = 3.034, P = 0.011). In 65 repeat biopsies, SV40-T antigen staining remained positive in 40 patients and became negative in the other 20 patients. The eGFR (42.6 ± 14.3 vs. 26.5 ± 12.3 mL·min·1.73 m), urine viral loads (median, 1.3 × 10vs. 1.4 × 10 copies/mL), and plasma viral load (median, 0 vs. 0 copies/mL) were all significantly lower in patients with negative SV40-T antigen staining than those with persistent BK involvement (all, P < 0.05). Five (3.8%) recipients lost their graft at diagnosis of BKVN, and 13 (9.8%) lost their graft during the follow-up period. The 1-, 3-, and 5-year graft survival rates after diagnosis of BKVN were 99.2%, 90.7%, and 85.7%, respectively. Higher pathologic stage correlated with lower allograft survival rate (χ = 6.341, P = 0.042).@*CONCLUSION@#Secondary rejection and persistent histologic infection in BKVN lead to poor prognosis.

Icariin protects against MPP-induced neurotoxicity in MES23.5 cells / 生理学报

Icariin is the major bioactive component of Epimedium and has been demonstrated to be a potential drug for age-related diseases. The present study was aimed to investigate the neuroprotective properties of icariin against 1-methyl-4-phenylpyridinium ion (MPP)-induced neurotoxicity in MES23.5 cells and the possible mechanisms. MTT assay showed that treatment with MPPattenuated the cell viability in a dose-dependent manner in MES23.5 cells. Icariin pretreatment resulted in an enhancement of survival. Immunocytochemistry analysis revealed that icariin treatment attenuated MPP-induced loss of tyrosine hydroxylase (TH) positive cells. Meanwhile, Western blot confirmed MPPsignificantly decreased the TH protein expression, and icariin pretreatment could reverse the toxic effect of MPP. Moreover, flow cytometry showed that MPP-induced decrease of the mitochondrial membrane potential could be partly restored by icariin. Furthermore, real-time RT-PCR and Western blot analysis demonstrated that icariin treatment restored the MPP-induced up-regulation of Bax and down-regulation of Bcl-2 mRNA and protein expressions. Western blot data also revealed the inhibitory effect of icariin on MPP-induced up-regulation of cleaved caspase-3. These findings provide the evidence that icariin has neuroprotective properties against MPP-induced neurotoxicity in MES23.5 cells and the mechanism might be related to the anti-apoptotic action of icariin.

The protective effect of ginsenoside Rg1 on dopaminergic neurons of substantia in the ovariectomized rat model of Parkinson's disease / 中国应用生理学杂志

<p><b>AIM</b>To investigate the neuroprotective effect of ginsenoside Rg1 on dopaminergic neurons of substantia nigra in ovariectomized rat model of Parkinson's disease and the possible mechanisms.</p><p><b>METHODS</b>Wistar female rats were ovariectomized and treated with vehicle, ginsenoside Rg1 or 17-beta estradiol intracerebroventricularly in the 6-OHDA induced rat model of Parkinson's disease. Immunohistochemistry was used to detect the tyrosine hydroxylase (TH) immunoreactive neurons and the protein expression of Bcl-2. Perls' iron staining was used to determine the changes of iron in substantia nigra (SN).</p><p><b>RESULTS</b>910 Rg1 or 17-beta estradiol treatment could ameliorate the rat's rotational behavior induced by apomorphine. 92) Rg1 or 17-beta estradiol treatment could increase TH immunoreactive neurons in the injured side of SN compared to the 6-OHDA group. (3) Iron staining in the injured side of SN was significantly increased comparing with the contralateral side in the 6-OHDA group. Rg1 or 17-beta estradiol treatment could reverse the increase of iron staining. (4) Both Rg1 and 17-beta estradiol treatment could increase Bcl-2 protein expression in the injured side of SN compared to the 6 OHDA group.</p><p><b>CONCLUSION</b>Ginsenoside Rg1 has estrogen-like activities and has neuroprotective effects on the dopaminergic neurons in the 6-OHDA induced ovariectomyzed(OVX) rat model of Parkinson's disease (PD). This effect may be attributed to attenuating iron overload and anti-apoptosis.</p>

Effect and mechanism on dopamine contents of striatum in rat model of Parkinson's disease ginsenoside Rg1 / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate effect and mechanisms on dopamine contents of striatum (Str) in the 6-OHDA induced rat model of Parkinson's disease (PD) by ginsenoside Rg1.</p><p><b>METHOD</b>Ovariectomized PD rats were treated with vehicle, ginsenoside Rg1, (10 mg x kg(-1)) or estrogen receptor (ER) antagonist ICI 182,780 for 14 d. The change of apomorphine-linduced rotational behavior in PD rats were observed. The high performance lipid chromotophotography (HPLC) was used to determine the contents of DA, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)in striatum.</p><p><b>RESULT</b>Rg1 treatment could ameliorate the PD rat's rotational behavior induced by apomorphine (P < 0.01). This effect could be blocked by ER antagonist ICI 182,780. The DA, DOPAC and HVA levels in the injured side of Str for PD rats were significantly decreased compared with the intact side (P < 0.01). Rg1, treatment could increase DA contents in the injured side of Str (P < 0.01). ICI 182,780 could completely block the neuroprotective effects of Rg1. The DA contents and its metabolites in the injured side of the ICI treatment group were significantly decreased compared with the Rg1 group (P < 0.01).</p><p><b>CONCLUSION</b>Ginsenoside Rg1 may have protective effects on the dopaminergic neurons for the 6-OHDA induced OVX rat model of PD, ER. May be involved in the protection action.</p>

Effects of ACE inhibitor on the calcium transient and calcium handling proteins in ventricular myocytes from rats with heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the influence of ACE inhibitor (perindopril) on the contractility and calcium transient and calcium handling proteins in ventricular myocytes from rats with experimental heart failure.</p><p><b>METHODS</b>Male Wistar rats were randomized to heart failure group treated with perindopril (CHF-T, 3 mg.kg(-1).d(-1)), heart failure group without treatment (CHF-C) and sham-operated group (PS) after heart failure was induced by constricting abdominal aorta for 16 weeks. All groups were further followed up for 12 weeks. Left ventricular myocytes were isolated, and single cell shortening fraction and [Ca(2+)](i) were simultaneously measured through laser scanning confocal microscope under the field stimulation (1.0 Hz). RT-PCR and Western blot were performed to evaluate the level of mRNA and protein of Na(+)-Ca(2+) exchanger (NCX(1)), sarcoplasmic Ca(2+)-ATPase (SERCA(2)) and phospholamban (PLB).</p><p><b>RESULTS</b>The fraction of cell shortening (FS%) and [Ca(2+)](i max) (nmol/L) were significantly smaller in group CHF-C than group PS (FS%: 7.51 +/- 1.15 vs 13.21 +/- 1.49; [Ca(2+)](i max): 330.85 +/- 50.05 vs 498.16 +/- 14.07; both P < 0.01). And in CHF-T group, FS and [Ca(2+)](i max) were greater than those in CHF-C group. In CHF-C group, the left ventricular mRNA of NCX(1) and PLB were significantly higher than those in PS group (R(NCX)(1)/beta-Actin: 0.51 +/- 0.12 vs 0.19 +/- 0.06, P < 0.01; R(PLB)/beta-Actin: 0.26 +/- 0.12 vs 0.20 +/- 0.08, P = 0.045), yet SERCA(2) mRNA was lower than PS group (0.48 +/- 0.10 vs 0.80 +/- 0.11, P < 0.01). In CHF-T group, the mRNA levels of NCX(1) and SERCA(2) were just in the midst of the CHF-C and PS group, and had statistical significance respectively (all P < 0.05). In CHF - C and CHF - T group, the protein levels of NCX(1) were 1.141 +/- 0.047 and 1.074 +/- 0.081 times PS group, respectively (both P < 0.05), and SERCA(2) protein levels were respectively 0.803 +/- 0.100 and 0.893 +/- 0.084 times as high as in PS group (both P < 0.05). The protein expression of NCX(1) and SERCA(2) were also different between CHF-C and CHF-T groups (both P < 0.05).</p><p><b>CONCLUSION</b>ACE inhibitor could improve cardiac function in CHF through directly enhancing the contractility of single myocardial cell, and these effects were probably mediated by its role in preventing the deleterious changes of calcium transient and calcium handling proteins in CHF.</p>

Microscopic autofluorescence study of cardiac cancer and normal gastric tissues / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the microscopic autofluorescent characteristics of cardiac cancer and autofluorescence distribution in different layers of gastric tissues.</p><p><b>METHODS</b>A double-channel laser scanning confocal microscopy with Argon ion laser (excitation wavelength 488 nm) and Helium-Neon laser (excitation wavelength 543 nm) were used to detect the autofluorescence emitted from 16 surgical specimens of cardiac cancer and corresponding normal gastric tissue. The autofluorescence image was analyzed between the cardiac cancer tissue and normal gastric tissue.</p><p><b>RESULTS</b>Autofluorescence was detected successfully in cardiac carcinoma and corresponding normal gastric corpus tissues of all 16 cases. In different layers of gastric tissue, fluorescence presented the strongest signal in submucosa,the second strong in luminal propria with fluorescence mostly distributed in the glands, fluorescence signal from gastric cancer was significantly decreased compared with those in the different layers of normal tissues (P< 0.01).</p><p><b>CONCLUSION</b>There are significant differences in the shape, color, distribution and fluorescence intensity of microscopic autofluorescence between cardiac cancer tissues and normal gastric corpus tissues.</p>

Effect of angiotensin converting enzyme inhibitor on the calcium transients and calcium handling proteins in ventricular myocytes from rats with heart failure / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Chronic heart failure (CHF) is associated with calcium transients and calcium handling proteins. Angiotensin converting enzyme (ACE) inhibitor has been demonstrated to have beneficial effect on CHF. Yet studies addressed to the relationship between ACE inhibitor and calcium transients in CHF are rare. The aim of this study was to investigate the influence of ACE inhibitor (perindopril) on the contractility and calcium transients and calcium handling proteins in ventricular myocytes from rats with experimental heart failure.</p><p><b>METHODS</b>Male Wistar rats were randomized to heart failure group treated with perindopril [CHF-T, 3 mg.kg(-1).d(-1)], heart failure group without treatment (CHF-C) and sham-operated group (PS). Heart failure was induced by abdominal aortic constriction. All groups were further followed up for 12 weeks. Left ventricular myocytes were then isolated. Single cell shortening fraction and [Ca(2+)]i were simultaneously measured by laser scanning confocal microscope under the field stimulation (1.0 Hz). Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot were performed to evaluate the changes of mRNA and protein of Na(+)-Ca(2+) exchanger (NCX1), sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) and phospholamban (PLB).</p><p><b>RESULTS</b>The fraction of cell shortening (FS%) and [Ca(2+)]imax (nmol/L) were significantly reduced in group CHF-C compared with group PS (FS%: 7.51 +/- 1.15 vs 13.21 +/- 1.49; [Ca(2+)]i max: 330.85 +/- 50.05 vs 498.16 +/- 14.07; both P < 0.01), and restored at least partially in CHF-T group. In CHF-C group, the left ventricular mRNA of NCX1 and PLB were significantly upregulated in comparing with PS group (RNCX1/beta-Actin: 0.51 +/- 0.12 vs 0.19 +/- 0.06, P < 0.01; RPLB/beta-Actin: 0.26 +/- 0.12 vs 0.20 +/- 0.08, P < 0.05), while SERCA2 mRNA was downregulated (0.48 +/- 0.10 vs 0.80 +/- 0.11, P < 0.01). The mRNA levels of NCX1 and SERCA2 in CHF-T group were between the CHF-C and PS group, and the differences of the latter two groups were significant (all P < 0.05). In CHF-C and CHF-T groups, the protein expression of NCX1 were 1.141 +/- 0.047 and 1.074 +/- 0.081 times of that in PS group respectively (both P < 0.05), and SERCA2 protein levels were 0.803 +/- 0.100 and 0.893 +/- 0.084 times of that in PS group respectively (both P < 0.05). The protein expression of NCX1 and SERCA2 in the CHF-C and CHF-T groups is significantly different (both P < 0.05).</p><p><b>CONCLUSION</b>ACE inhibitor could improve cardiac function of failing heart through directly enhancing the contractility of single cardiomyocyte, and these effects are probably mediated by its roles in preventing the deleterious changes of calcium transients and calcium handling proteins in CHF.</p>

Smad7 overexpression inhibits epithelial-mesenchymal transition in peritoneal fibrosis rat model / 中华肾脏病杂志

Objective To investigate the role of overexpression of Smad7,the inhibitory factor of TGF-?/Smads signaling,in epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells.Methods Peritoneal fibrosis rat model was built by daily intraperitoneal injection with 4.25% Dineal (100 ml/kg) and lipopolysaccharide(LPS) (0.6 mg/kg) at day 8,10,12,22,24,26. Smad7 or control empty vectors was transferred at day 0,14 and was induced by doxycline in the daily drinking water (200 mg/L).Rats were sacrificed on day 28 and the expression of TGF-beta/ Smads,?-SMA and E-cadherin was examined.Results Compared with normal rats,empty vector rats showed higher expression of phosphorylated Smad2/3.?-SMA expression was elevated but E-cadherin was reduced.Under electron microscope,the mesothelial cells removed to submesothelial zone and showed large bundles of actin microfilaments and dense bodies within the cytoplasm. Basement membrane was broken.After induction of Smad7 in peritoneal fibrosis rats,the morphology of mesothelial ceils normalized partly,phosphorylated Smad2/3 was reduced.Moreover,expression of E-cadherin was increased,expression of?-SMA was dramatically reduced.Conclusion Inhibition of TGF-?/Smad signaling by Smad7 overexpression may inhibit the epithelial-mesenchymal transition of mesothelial cell,which may provide a new therapeutic method for peritoneal fibrosis by overexpression of Smad7.

Effects of Smad7 on transdifferentiation and collagen I synthesis in AGE-stimulated NRK52E cells / 中华内分泌代谢杂志

Objective To investigate the effects of smad7 on transdifferentiation and collagenⅠsynthesis in advanced glyeosylation end-products(AGE)-stimulated NRK52E cells.Methods NRK52E cells were transferred by pTet-on plasmid system and the cell lines of doxycycline(Dox)-regulated Smad7 expression were selected for the study.Transnuclear location of p-Smad2/3 was examined with immunocytochemistry.The mRNA and protein expressions of Smad7,?-SMA,E-cadherin,collagenⅠwere detected with RT-PCR and Western blot. Results AGE-induced expressions of Smad7 mRNA and protein were further increased in NRK52E cells by the addition of Dox in a dose-dependent manner.Overexpression of Smad7 caused a marked inhibition of p-Smad2/3 transnuclear location at 30 min(68.3% vs 31.2%,P