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ObjectiveTo investigate whether menaquinone-4 （MK-4） can exert a protective effect against carbon tetrachloride （CCl4）-induced acute liver injury （ALI） in mice by alleviating ferroptosis. MethodsAfter adaptive feeding， adult male ICR mice， aged 8 weeks， were divided into Control group， MK-4 group， CCl4 model group （6-hour， 12-hour， and 24-hour）， and MK-4+CCl4 group （6-hour， 12-hour， and 24-hour）， with 6 mice in each group. The mice in the Control group were given intraperitoneal injection of an equal dose of corn oil； the mice in the MK-4 group were given intraperitoneal injection of 40 mg/kg MK-4 solution， followed by an equal dose of corn oil after 1 hour； the mice in the MK-4+CCl4 group （6-hour， 12-hour， and 24-hour） were given intraperitoneal injection of 40 mg/kg MK-4 solution， and after 1 hour， the mice in this group and the CCl4 model group （6-hour， 12-hour， and 24-hour） were given intraperitoneal injection of 0.3 mL/kg CCl4 solution， with samples collected at 6， 12， and 24 hours. HE staining was used to observe the pathological changes of mouse liver； Prussian blue staining was used to observe iron accumulation in liver tissue； a biochemical analyzer was used to measure the serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）； related kits were used to measure the levels of tissue iron content and the oxidative stress indices malondialdehyde （MDA） and glutathione （GSH） in liver homogenate； RT-PCR was used to measure the expression levels of ferroptosis marker genes （acyl-CoA synthetase long-chain family member 4 ［ACSL4］， prostaglandin-endoperoxide synthase 2 ［PTGS2］， and glutathione peroxidase 4 ［GPX4］） and iron metabolism-related genes （hemojuvelin ［HJV］， transferrin receptor 1 ［TFR1］， and ferroportin ［FPN］）， and Western blot was used to measure the protein expression level of GPX4. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsIn the aging study， compared with the Control group， the CCl4 model group （6-hour， 12-hour， and 24-hour） had significant increases in liver weight coefficient and the serum levels of ALT and AST （all P<0.05）， and HE staining also showed that liver injury gradually aggravated over time. Meanwhile， compared with the CCl4 model group （6-hour， 12-hour， and 24-hour）， the MK-4+CCl4 （12-hour） group had significant reductions in liver weight coefficient and the serum levels of ALT and AST （all P<0.05）， with a reduction in the necrotic area of liver tissue， and therefore， 12-hour mouse tissue samples were used for detection in the following study. Compared with the Control group， the CCl4 group had a significant increase in MDA and a significant reduction in GSH （both P<0.05）， and compared with the CCl4 group， the MK-4+CCl4 group had a significant reduction in MDA and a significant increase in GSH （both P<0.05）. Compared with the Control group， the CCl4 group had significant increases in the key ferroptosis indices ASCL4 and PTGS2 and a significant reduction in GPX4 （all P<0.05）； compared with the CCl4 group， the MK-4+CCl4 group had significant reductions in the mRNA expression levels of ASCL4 and PTGS2 and a significant increase in the mRNA expression level of GPX4 （all P<0.05）. Western blotting showed that compared with the Control group， the CCl4 group had a significant reduction in the protein expression level of GPX4 （P<0.05）， and compared with the CCl4 group， the MK-4+CCl4 group had a significant increase in the protein expression level of GPX4 （P<0.05）. Prussian blue staining showed that compared with the Control group， the CCl4 group had a significant increase in iron accumulation； after MK-4 intervention， compared with the CCl4 group， the MK-4+CCl4 group had a significant reduction in iron accumulation. As for the measurement of iron metabolism genes in mouse liver， compared with the Control group， the CCl4 group had a significant increase in iron content， significant reductions in the mRNA expression levels of FPN and HJV， and a significant increase in the mRNA expression level of TFR1 （all P<0.05）； after protection with MK-4， there was a significant reduction in iron content， significant increases in the mRNA expression levels of FPN and HJV， and a significant reduction in the mRNA expression level of TFR1 （all P<0.05）. ConclusionMK-4 intervention in advance can alleviate CCl4-induced ALI in mice， possibly by inhibiting ferroptosis and improving the expression of iron metabolism-related genes in mouse liver.
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Cholestatic liver disease is a common hepatobiliary disease caused by bile deposition in the liver due to the disorders of bile production, excretion, and metabolism. At present, the pathogenic factors for cholestatic liver disease have not been fully elucidated, but some researchers believe that environmental factors may play an important role in it. As environmental pollutants, phthalic acid esters (PAE) have been confirmed to interfere with human endocrine system, exert a potential toxic effect on the human body, endanger liver and kidney function, and increase the risk of intrahepatic cholestasis. On this basis, this article reviews the association between PAE and cholestatic liver disease and summarizes related clinical studies, animal experimental studies, in vitro experimental studies, and potential mechanisms, so as to provide ideas and references for the prevention and clinical treatment of cholestatic liver disease.
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Research on the pathogenesis of liver diseases has attracted great attention. Endoplasmic reticulum stress (ERS) is a self-protective mechanism of cells, but sustained and severe ERS can induce apoptosis, autophagy, and ferroptosis, among which ferroptosis has been a research hotspot in recent years. Ferroptosis is mainly characterized by the accumulation of iron-dependent lipid peroxides and plays a key role in the development and progression of liver diseases, but there are currently few studies on the involvement of ERS in ferroptosis in liver diseases. This article summarizes the research advances in ERS-related signaling pathways, the mechanism of ferroptosis, and the involvement of ERS in liver diseases, so as to provide more ideas for research on the treatment of liver diseases.
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Objective:To compare the value of NoSAS score, STOP-BANG questionnaire (SBQ) and Epworth Sleepiness Scale (ESS) in assessing the risk of obstructive sleep apnea hypopnea syndrome (OSAHS) in patients with respiratory disease (RD).Methods:The clinical data, NoSAS, SBQ and ESS scores of 190 patients who underwent overnight polysomnography (PSG) were collected. According to the receiver operating characteristic (ROC) curve, with different apnea-hypopnea index (AHI) as the judgment cutoff, the sensitivity, specificity, positive predictive value, negative predictive value, diagnostic odds ratio (DOR) and accuracy of the three scales were compared.Results:With AHI ≥5 times/h as the cutoff, the area under the ROC curve (AUC) of NoSAS and SBQ were 0.833 and 0.729, respectively, indicating that both have predictive value for mild OSAHS. Among them, NoSAS had a larger DOR value (16.150), indicating that NoSAS had the higher accuracy in assessing the risk of mild OSAHS. When AHI>15 times/h was used as the cutoff, the AUC value of NoSAS was 0.704, indicating that it has predictive value for moderate OSAHS. When AHI>30 times/h was used as the cutoff, the AUC value (0.706) and DOR value (6.527) of SBQ were high, indicating that it has predictive value and good accuracy for severe OSAHS. The SBQ is more sensitive than NoSAS and ESS when evaluating patients at high risk for OSAHS ( SBQ≥3). Conclusions:When evaluating the risk of mild and moderate OSAHS in RD patients, NoSAS is better than SBQ and ESS, and when evaluating severe OSAHS, SBQ is better than NoSAS and ESS. In clinical work, appropriate predictive tools should be selected according to the actual situation to assess the risk of OSAHS, so as to formulate and implement early intervention plans based on the assessment results.
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Objective@#Cisplatin resistance is a huge problem encountered in ovarian cancer treatment. Our study probed the roles and the underlying mechanisms of lncRNA MCF2L-AS1 in ovarian cancer cisplatin-resistance. @*Methods@#SKOV3 and IGROV-1 cells were subjected to gradually increasing concentrations of cisplatin to construct ovarian cancer cisplatin-resistance cells. Cell proliferation was evaluated by cell counting kit-8 and colony formation assays. Cell apoptosis was assessed using Annexin V and PI staining. The relationships between SP1, MCF2L-AS1 and insulin-like growth factor-2 mRNA binding protein 1 (IGF2BP1) were verified by RNA pull-down, RIP, ChIP and dual-luciferase reporter gene assay, respectively. Tumor xenograft experiment was employed to evaluate the effects of MCF2L-AS1 silencing on ovarian cancer cisplatin-resistance in vivo. TUNEL staining and immunohistochemistry were performed in tumor tissue. @*Results@#MCF2L-AS1 and IGF2BP1 were upregulated in cisplatin-resistant cells. MCF2L-AS1 silencing suppressed cell proliferation of cisplatin-resistant cells, while promoted the apoptosis, suggesting that MCF2L-AS1 knockdown suppressed ovarian cancer cells cisplatin-resistance. Meanwhile, MCF2L-AS1 silencing enhanced cisplatin sensitivity in ovarian cancer parental cells and IGF2BP1 overexpression impaired cisplatin sensitivity of parental cells. MCF2L-AS1 activated IGF2/MEK/ERK pathway through interacting with IGF2BP1. Transcription factor SP1 activated MCF2L-AS1 expression. MCF2L-AS1 knockdown inhibited ovarian cancer cisplatin-resistance in vivo. @*Conclusion@#SP1-induced MCF2L-AS1 promoted ovarian cancer cisplatin-resistance through activation of IGF2/MEK/ERK pathway via interacting with IGF2BP1.
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Objective:To explore the effect of nurse-led management model in adherence of patients with obstructive sleep apnea hypopnea syndrome (OSAHS) who underwent non-invasive mechanical ventilation.Methods:92 patients with severe OSAHS diagnosed by polysomnography(PSG) and treated with non-invasive mechanical ventilation in Tianjin medical university general hospital from September 2019 to August 2020 were enrolled. The patients were divided into intervention group (45 cases) and control group (47 cases) by random number table. Then, basing on routine treatment and subsequent visit, the patients in intervention group received regular telephone follow-up interviews within one week of ventilator purchasing, and the interview was based on a standard telephone follow-up manuscript designed by Duffy and lasted for six months. The patients in control group received routine nursing treatment and regular subsequent visit, and were not followed up by telephone, but were encouraged to have telephone consultation. The Epworth sleepiness scale(ESS) scores of the two groups before and after the intervention and the compliance of non-invasive mechanical ventilation of the two groups after the intervention were compared.Results:After the intervention, the ESS scores of the two groups were lower than those before the intervention ( P<0.001), and the ESS scores of the intervention group were lower than those of the control group ( P<0.001). After the intervention, the compliance of noninvasive mechanical ventilation in the intervention group was better than that in the control group ( P<0.001). Conclusions:The nurse-led management model in combination with telephone follow-up can improve the sleepiness of patients and the adherence of using non-invasive mechanical.
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Objective: To investigate the clinical effect of entecavir combined with pegylated interferons in the patients with hepatitis B.Methods: Totally 72 patients with hepatitis B were randomly divided into the experimental group and the control group with 36 ones in each.The patients in the experimental group were treated with entecavir combined with pegylated interferons, and those in the control group were treated with entecavir.The clinical indicators in the two groups were detected and compared after the 24-week, 48-week and 6-month treatment.The adverse drug reactions in the two groups were recorded and compared.Results: After the 24-week treatment, the differences in the clinical indicators between the groups were not statistically significant (P >0.05).After the 48-week and 6-month treatment, the clinical indicators in the experimental group were obviously higher than those in the control group, and the differences were statistically significant (P 0.05).Conclusion: Compared with entecavir, pegylated interferon combined with entecavir in the treatment of hepatitis B shows better clinical effect and security, which is more worthy of clinical promotion.
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Objective To investigate the effect of Vitamin D (VitD) on intraperitoneal fat coefficient,monocyte/macrophage chemoattractant protein and macrophage infiltration in adipose tissue of infantile rats with obesity.Methods A total of 45 weanling female SD rats were randomly divided into control group (group N),obesity model group(group OB) and VitD intervention group(group VitD),and each group had 15 rats.The rats of group N were fed with basic diet,and the rats in group OB and group VitD were fed with high-fat diet.The rats of group VitD were administrated intragastrically with VitD 5 μg/(kg · d)(equivalent to 400 IU VitD for human infants) for 6 weeks,while the rats of group OB and group N were given plant oil [5 mL/(kg · d)] for 6 weeks instead.The body weight of rats were recorded once every week,and Lee's indexes were calculated.The fat mass in enterocoelia were wcighted after 6 weeks.The levels of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 α (MIP-1 α) in serum were detected by adopting enzyme-linked immunosorbent assay.The specimens of adipose tissue were observed and the number of adipocyte was counted through hematoxylin-eosin stain.The protein expressions of MCP-1,MIP-1 α and F4/80 in adipose tissue were determined by immunohistochemistry,and the mRNA expressions of MCP-1,MIP-1α and nuclear factor (NF)-κB in adipose tissue were determined by real time quantitative polymerase chain reaction(qPCR),then the correlation analysis with body weight,Lee's index and fat mass in enterocoelia were conducted.Results After 6 weeks with high-fat diet,the body weight,intraperitoneal fat coefficient,serum levels ofMCP-1 and MIP-1α in group OB[(244.1 ± 16.2) g,(3.25 ±0.63)％,(2 275.2 ±229.3) ng/L,(190.4 ± 61.9) ng/L] significantly increased compared with those of group N [(224.2 ± 10.9) g,(2.43 ± 0.47) ％,(1 522.1 ±577.1) ng/L,(63.6 ±31.6) ng/L] and group VitD[(214.0± 12.5) g,(2.04 ±0.64)％,(1 863.4 ± 477.0) ng/L,(120.3 ± 29.5) ng/L],and the differences were significant (all P ＜ 0.05).The adipose cells ranged orderly in group N and group VitD;the structure was disordered in group OB with various shapes and sizes of adipose cells and the excessively expanded adipose cells existed with many small newborn adipose cells.Immunohistochemistry showed that the protein expressions of MCP-1,MIP-1α and F4/80 in adipose tissue in group OB(130 944.5 ±10 706.1,174 354.8 ±65 267.8,51 701.9 ± 50 105.1) significantly increased compared with those of group N (47 394.5 ± 9 261.9,54 376.7 ± 36 436.9,23 370.3 ± 16 613.1),and the differences were significant (all P ＜ 0.01);the protein expressions of MCP-1,MIP-1α and F4/80 in adipose tissue in group VitD (102 967.2 ± 9 329.3,48 659.8 ± 43 553.8,25 604.9 ± 11 411.6) significantly decreased compared with those of group OB,and the differences were significant (all P ＜ 0.01).The qPCR showed that mRNA expressions of MCP-1,MIP-1 α and NF-κB in adipose tissue in group OB (2.78 ± O.90,7.10 ± 1.85,1.50 ± 0.16) significantly increased compared with those of group N (0.88 ± 0.18,0.99 ± 0.80,1.00 ± 0.28),and the differences were significant (all P ＜ 0.05);the mRNA expressions of MCP-1,MIP-1α and NF-κB in adipose tissue in group VitD(1.73 ±0.51,1.59 ± 1.09,0.72 ±0.30) significantly decreased compared with those of group OB,and the differences were significant (all P ＜0.05).There was no significant difference in Lee's indexes among the 3 groups (F =0.351,P =0.711).At the age of 9 months age,the mRNA expression levels of MCP-1,MIP-1α and NF-κB in adipose tissue of infantile rats were positively correlated with body weight and intra-peritoneal fat coefficient(r =0.738,0.517,0.762,0.693,0.519,0.557,all P ＜ 0.05),but there was no correlation with the Lee's index(r =0.322,0.317,-0.023,all P ＞0.05).Conclusions VitD supplement can suppress the obesity induced by high-fat-diet,and the possible mechanism is that VitD reduce the expression of monocyte/macrophage chemoattractant protein and macrophage infiltration in adipose tissue through regulating NF-κB signal pathway.
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OBJECTIVE:To provide reference for rational application of cephalosporins in the clinic. METHODS:The applica-tion of cephalosporins antibiotics in our hospital during 2010-2014 was analyzed dynamically in respects of consumption sum, DDD,DDC,DDDs,etc. RESULTS:During 2010-2014,the proportion of total consumption sum of antibiotics in total consump-tion sum kept below 30%,and decreased year by year,decreasing from 27.35% in 2010 to 14.70% in 2014. Among antibiotics, the consumption sum and DDDs of cephalosporins were the highest;consumption sum decreased year by year,decreasing from 44.50% in 2010 to 30.49% in 2014;DDDs increased year by year,increasing from 11.00×104 in 2012 to 14.22×104 in 2014. The consumption sum and DDDs of second generation cephalosporins were the highest. The consumption sum of cefotiam ranked the first place;DDDs of cefprozi ranked the first place during 2010-2011,while cefotiam ranked the first place during 2012-2014. DDC of cefpirome was the highest during 2010-2011,and that of cefamandole was the highest during 2012-2014,indicating it was expensive. The serial number ratio of cefprozi and cefuroxim was always >1 during those years,which indicated it was cheap and used frequently;that of most drugs were close to 1. CONCLUSIONS:The application of cephalosporins in our hospital tend to be rational,but the propaganda and supervision of rational use of antibiotics should be further strengthened.
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Vitamin D has a wide range of biochemical effects. Insufficiency/ deficiency of vitamin D increases the risk of insulin resistance by ways of inflammation,adipocytokines,oxidative stress and mitochondria function,it could lead to metabolic disorder of glucose and lipid,which closely relates to the incidence and development of obesity and metabolic syndrome on children. This paper presents the relationship between vitamin D with obesity and metabolic syndrome on children,states the possible mechanisms of regulation of glucose/ lipid metabolism and insulin resistance by vitamin D.
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<p><b>OBJECTIVE</b>To explore the effects and the molecular mechanisms of 4-phenylbutyric acid (PBA) on carbon tetraehloride (CCl4)-induced acute liver injury in mice.</p><p><b>METHODS</b>Sixty adult, healthy, male ICR mice were divided equally into the control group, PBA group, CCl4 12 h group, CCl4 24 h group, CCl4 48 h group, CCl4 72 h group, PBA+CCl4 12 h group, PBA+CCl4 24 h group, PBA+CCl4 48 h group, and PBA+CCl4 72 h group. The CCl4 groups and the PBA+CCl4 groups were intraperitoneally (i.p.) injected with CCl4 (300 mL/kg). In the PBA+CCl4 groups, the mice were i.p. injected with PBA (400 mg/kg). All mice were sacrificed to collect blood and liver specimens at different time points after the CCl4 treatment. Serum alanine aminotransferase (ALT) was detected. Histological examination was performed using hematoxylin-eosin staining and light microscopy, and apoptosis was detected using terminal transferase dUTP nick end labeling. The hepatic distribution of proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry. The hepatic protein expression of glucose-regulated protein (GRP78), C/EBP homologousprotein (CHOP), phosphorylated c-Jun N-terminal kinases (p-JNK), phosphorylated eukaryotic initiation factor 2a subunit (p-eIF2a), phosphorylated serine threonine kinase (p-akt), and nuclear factor-kappa B p65 (NF-kappa Bp65) were determined by western blot.</p><p><b>RESULTS</b>The serum ALT level in the PBA+CCl4 groups was reduced as compared with that in the CCl4 groups at the various time points examined.The liver-to-body weight ratio of two groups showed a significant difference only at the 48 h time point (P<0.01). PBA reduced the degree of hepatic necrosis and apoptosis caused by CCl4, and reduced the expression of hepatic GRP78 and other endoplasmic reticulum stress-related proteins (P<0.01). The protein levels of p-akt, NF-kappa Bp65 and PCNA was significantly decreased in the PBA+CCl4 groups (P<0.01).</p><p><b>CONCLUSION</b>The endoplasmic reticulum stress inhibitor PBA alleviated acute hepatic necrosis and apoptosis but restrained hepatic proliferation.</p>
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Animals , Male , Mice , Alanine Transaminase , Apoptosis , Carbon Tetrachloride , Chemical and Drug Induced Liver Injury , Endoplasmic Reticulum Stress , HSP70 Heat-Shock Proteins , Membrane Proteins , Mice, Inbred ICR , NF-kappa B , Phenylbutyrates , PhosphorylationABSTRACT
Objective To evaluate the incidence,severity,risk tactors and impact to prognosis of acute kidney injury (AKI) in patients with severe traumatic brain injury (sTBI) by using acute kidney injury network (AKIN) classification system.Methods A retrospective analysis was carried out in 136 patients with sTBI hospitalized between January 2007 and May 2011.Demographic data,admission evaluation (whether with hernia or not on admission,systolic pressure and mean arterial blood pressure,serum creatinine and urea nitrogen,and blood glucose),outcome at 6 months post-injury and mortality were collected.Renal function was assessed using AKIN criteria.The patients were divided into two groups based on the presence or absence of AKI (non-AKI group and AKI group).According to the severity of AKI,AKI group was further classified as AKI grade 1 group,AKI grade 2 group and AKI grade 3 group.The differences among groups were analyzed.Results According to AKIN classification system,31 (23％) out of the 136 patients were diagnosed as being with AKI,including 21 cases (68％) in AKI grade 1 group and 10 cases (32％) in AKI grade 2 and 3 groups.The patients at older age and with lower Glasgow coma scale (GCS) on admission,higher levels of serum creatinine and blood urea nitrogen on admission were prone to AKI.As compared with TBI patients with normal renal function,TBI patients associated with AKI had higher mortality and worse outcome.Conclusions AKI is a common complication of patients with sTBI.AKIN classification system can early diagnose AKI in sTBI patients and may contribute to improvement of the outcome.
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The correlation of single nucleotide polymorphism (SNP) rs10569304 on the second expressed region of hole gene and congenital heart disease (CHD) of human being, and the effect of hole gene on CHD were investigated. 179 patients with CHD as CHD group and 183 healthy people as control group were selected in the case-control study. DNA was abstracted from the peripheral blood by phenol-chloroform method. Primer was designed for the flanking sequence of SNP rs10569304 on the second expressed region of hole gene. The genotype was identified by PCR degenerative acrylamide electrophoresis with amplification products. Then the three amplification products received sequencing. By chi-square test, the genotype frequency and allele frequency in CHD group and control group were analyzed. There was insertion-deletion (GCC/-) of SNP rs10569304 which corresponded to alleles of A and B in Southern Chinese people. The genotype frequency and allele frequency in control group and CHD group were met the Hardy-Weinberg equilibrium. By chi-square test, in control group and CHD group, the genotype frequency of AA (insertion homozygous), AB (insertion-deletion heterozygous) and BB (deletion homozygous) was 21.31%, 54.09%, 24.59% and 16.75%, 46.36%, 36.87%, respectively. The distributional difference of genotype frequency had statistical significance (chi (2)=6.51, P<0.05); The allele frequency of A and B was 48.36% and 51.64% in control group, 39.94% and 60.06% in CHD group, respectively. The distributional difference of allele frequency had statistical significance (chi (2)=5.20, P<0.05). Meanwhile, by contrast with the control group, the BB genotype frequency and B allele frequency in CHD group was higher, but the AA and AB frequency was lower. There was higher risk to suffer from CHD involving B allele. BB genotype had 1.907-fold increased risk of developing CHD according to AA genotype (P<0.05). It is concluded that there is insertion-deletion (GCC/-) of SNP rs10569304 in the Southern Chinese people, and the people whose hole gene involving BB genotype have higher risk to suffering from CHD.
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Objective To compare the diagnostic clinical significance between loop electrosurgical excision procedure (LEEP) and colposcopical biopsy for cervical intracpithelial neoplasia(CIN). Methods 130 cases of pa-tients diagnosed as CIN under colposcopical biopsy were treated by LEEP in court of gynecology clinic. The conven-tional pathologic diagnosis was recorded in all conization specimens. Results The coincidence rate between colpo-scopical biopsy and LEEP biopsy in CIN Ⅰ, CIN Ⅱ, CIN Ⅲ (not comprised carcinoma in situ) was 55.26%,66.10% ,78.79% respectively;The total coincidence rate was 66.15%. The accuracy of colposcopic biopsy for diag-nosing CINⅢ was higher than that for CIN Ⅰ and CIN Ⅱ,but there was no statistical difference. Conclusion Colpo-scopical biopsy for cervical lesions can be achieved for the frist time the results of pathology, have limitations. LEEP biopsy can compensate partially the deficiency of colposcopic biopsy. In a dear diagnosis of CIN, LEEP biopsy and colposcopical biopsy may complement each other, and achieve thcrpeutic effects.
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In current study, the expressions of protein kinase C (PKC)-alpha, betaI and betaII as well as their correlation to the expression of transforming growth factor-betaI (TGF-betaI) and vascular endothelial growth factor (VEGF) were investigated in glomeruli of normal renal tissues taken from human kidney tumors and kidney tissues from patients with diabetic nephropathy (DN). The accumulation of glomerular extracelluar matrix (ECM) was determined by PAS staining, the expressions of PKC-a, PKC-betaI, PKC-betaII, TGF-betaI and VEGF were measured by semi-quantitative immunohistochemistry. Our results showed that in glomeruli of normal renal tissues, PKC-alpha and betaII had a strong expression whereas the expression of PKC-betaI was weak; in glomeruli of DN patients, the expressions of PKC-alpha, PKC-betaI, VEGF and TGF-betaI and the accumulation of ECM increased significantly, but the expression of PKC-betaII decreased markedly. Meanwhile, the expressions of PKC-alpha and betaI had a positive correlation to the expressions of VEGF and TGF-betaI respectively, whereas PKC-betaII showed no correlation to VEGF and TGF-betaI. It is concluded that the expressions of PKC-alpha, betaI and betaII in glomeruli of normal subjects and DN patients are different. PKC-alpha seems to play a critical role in human DN by up-regulating VEGF expression, whereas PKC-betaI is relatively important for the up-regulation of TGF-betaI and the accumulation of ECM under diabetic conditions.
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In current study, the expressions of protein kinase C (PKC)-α, βⅠ and βⅡ as well as their correlation to the expression of transforming growth factor-βⅠ (TGF-βⅠ) and vascular endothelial growth factor (VEGF) were investigated in glomeruli of normal renal tissues taken from human kidney tumors and kidney tissues from patients with diabetic nephropathy (DN). The accumulation of glomerular extracelluar matrix (ECM) was determined by PAS staining, the expressions of PKC-α,PKC-βⅠ, PKC-βⅡ, TGF-βⅠ and VEGF were measured by semi-quantitative immunohistochemistry.Our results showed that in glomeruli of normal renal tissues, PKC-α and βⅡ had a strong expression whereas the expression of PKC-βⅠ was weak; in glomeruli of DN patients, the expressions of PKC-α,PKC-βⅠ, VEGF and TGF-βⅠ and the accumulation of ECM increased significantly, but the expression of PKC-βⅡ decreased markedly. Meanwhile, the expressions of PKC-α and βⅠ had a positive correlation to the expressions of VEGF and TGF-βⅠ respectively, whereas PKC-βⅡ showed no correlation to VEGF and TGF-βⅠ. It is concluded that the expressions of PKC-α, βⅠ and βⅡ in glomeruli of normal subjects and DN patients are different. PKC-α seems to play a critical role in human DN by up-regulating VEGF expression, whereas PKC-βⅠ is relatively important for the up-regulation of TGF-βⅠ and the accumulation of ECM under diabetic conditions.
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The different sera proteomic components between uremia patients and normal subjects were studied through two-dimensional gel electrophoresis technique. Immobilized pH gradient twodimensional polyacrylamide gel electrophoresis (2DE), silver staining, ImageMaster 2D 5.0 analysis software, matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDITOF-TOF-MS) and IPI human database searching were used to separate and identify the proteome of the sera from the patients with uremia. The results showed that satisfactory 2DE patterns of the serum proteins were obtained. Twenty-six protein spots showed significant difference in quantity in uremia patients, and 20 protein spots were identified by MALDI-TOF-TOF-MS. It was concluded that good reproducibility could be obtained by applying immobilized pH gradient 2DE to separate and identify the proteome in serum, which provided the foundation for the further study on uremia toxins pertaining to protein.
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The different sera proteomic components between uremia patients and normal subjects were studied through two-dimensional gel electrophoresis technique. Immobilized pH gradient two-dimensional polyacrylamide gel electrophoresis (2DE), silver staining, ImageMaster 2D 5.0 analysis software, matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-TOF-MS) and IPI human database searching were used to separate and identify the proteome of the sera from the patients with uremia. The results showed that satisfactory 2DE patterns of the serum proteins were obtained. Twenty-six protein spots showed significant difference in quantity in uremia patients, and 20 protein spots were identified by MALDI-TOF-TOF-MS. It was concluded that good reproducibility could be obtained by applying immobilized pH gradient 2DE to separate and identify the proteome in serum, which provided the foundation for the further study on uremia toxins pertaining to protein.
Subject(s)
Blood Protein Electrophoresis , Blood Proteins/analysis , Case-Control Studies , Electrophoresis, Gel, Two-Dimensional/methods , Proteome/analysis , Proteome/chemistry , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Uremia/bloodABSTRACT
Objective To establish and optimize the two-dimensional gel electrophoresis technical platform for the blood serum proteome research in patients with end stage renal disease(ESRD).Methods Immobiline pH gradients isoelectric focusing was used as the first dimensional gel electrophoresis and the vertical SDS-PAGE was used as the second dimensional gel electrophoresis(2-DE).The 4 differentially expressed protein spots were identified by mass spectrometry.Results Satisfactory 2-DE maps of ESRD patients serum protein were obtained and there were some differentially protein spots between the 2-DE maps of ESRD patients and normal controls.Conclusions The 2-DE technology for the serum proteome of ESRD patients is set up.
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Objective To investigate the effects of 1,25-dihydroxyvitamin D_3 on the bone metabolism of primary osteoporosis.Methods Female New Zealand white rabbits aged 8 months were ovariectomized bilaterally as models of postmenopausal osteoporosis and they were randomly divided into 4 groups: pseudo-ovariectomized group(Sham group),ovariectomized group(OVX group),calcii gluconas group(OC group),calcii gluconas and 1,25-dihydroxyvitamin D_3 group(OCR group).Both female New Zealand white rabbits aged 3 years and male New Zealand white rabbits aged 4 years were selected as models of senile osteoporosis.They were randomly divided into 3 groups:control group,calcii gluconas group(Calcium group),calcii gluconas and 1,25-dihydroxyvitamin D_3 group(CR group).Rabbits in OC group and Calcium group were given calcii gluconas and in OCR group and CR group were given calcii gluconas and 1,25-dihydroxyvitamin D_3.The bone metabolic biochemical indexes were determined among all the experimental animals after they were given drug for 8 weeks.Results After the experimental animals were given drug for 8 weeks,the serum calcium(Ca),serum phosphorus(P) and alkaline phosphatase(ALP) of OCR group were significantly higher than those of OVX group and OC group(all P