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Krüppel-like transcription factor 2 (KLF2) plays a key regulatory role in endothelial inflammation, thrombosis, angiogenesis and macrophage inflammation and polarization, and up-regulation of KLF2 expression has the potential to prevent and treatment atherosclerosis. In this study, trichostatin C (TSC) was obtained from the secondary metabolites of rice fermentation of Streptomyces sp. CPCC 203909 as a KLF2 up-regulator by using a high throughput screening model based on a KLF2 promoter luciferase reporter assay. TSC significantly inhibited the adhesion of tumor necrosis factor-α (TNFα) induced monocytes (THP-1) to human umbilical vein endothelial cells (HUVECs). Western blot results showed that TSC decreased TNFα induced the protein expression increase of vascular cell adhesion molecule-1 (VCAM-1), and thereby inhibited endothelial inflammation. The results of histone deacetylase (HDAC) overexpression and molecular docking experiments showed that TSC upregulated the expression of KLF2 by inhibiting subtypes of HDAC 4/5/7. In conclusion, this study suggests that TSC up-regulates the expression of KLF2 through inhibiting HDAC 4/5/7 and thus inhibits TNFα induced endothelial inflammation, and it has the potential to prevent and treat atherosclerosis.
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As mentioned in this paper, the curriculum team of biotechnological pharmaceutics in Binzhou University reoriented the curriculum objective based on the educational policy: fostering virtue through education and consolidating fundamental spirit and soul. Additionally, the team drew on cutting-edge scientific and technological developments, social hotspots, national spirit, innovative thinking, dedication spirit and other elements, conducted in-depth study on the ideological and political elements of the subject and organically integrated them with the contents such as genetic engineering, cellular engineering, fermentation engineering, enzyme engineering, protein engineering, and established online and offline ideological and political database. Furthermore, with the aid of teaching apps like ‘Rain Classroom’, the teaching models include lecture, case-based teaching, group discussion, and blended teaching for the subject. In the meantime, the ideological and political educational requirements were integrated into the curriculum evaluation system. Taking the genetic engineering pharmaceutics as an example, reform and practice for the ideological and political education for the undergraduate subject, biotechnological pharmaceutics, was applied. This paper expatiated the teaching practice of the ideological and political education, and reviewed the outcomes of the curriculum reform over these years in an effort to formulate a set of all-round programs for the reform and practice of the ideological and political education that can be replicated and improved continuously. This paper aims not only in developing high-caliber biomedical talents with a strong sense of patriotism and social responsibility, but also in providing a reference for the teaching reform of related subjects.
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Mesenchymal stem cell (MSC) is widely used in cell therapy because of its high proliferative and multi directional differentiation potential as well as its low immunogenicity. The transplantation of MSC can help the repair of the injured organs, however, the MSC transplanted to the local organs are affected by oxidative stress and lead to premature aging or apoptosis. Heme oxygenase 1 (HO1) is a key ratelimiting enzyme in the process of heme metabolism, which has the functions of antiinflammation, antioxidation, antiapoptosis, antiaging, reducing cell damage and promoting angiogenesis. Induced high expression of HO1 in MSC could increase the ability of MSC against oxidative stress injury, delay the senescence and apoptosis of MSC, and alleviate cell injury. In this reviews, the research progress of HO1 on antioxidative stress injury of MSC.
Subject(s)
Humans , Apoptosis , Cell Differentiation , Heme Oxygenase-1/metabolism , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Oxidative StressABSTRACT
Three tricyclic [6,5,7] and six tetracyclic [6,5,5,5] novel indole alkaloids were synthesized and evaluated on triglyceride inhibitory activities for the first time. Among them, compound 4c showed the most potent activity with IC50 value of 6.35 μmol·L-1. Meanwhile, compound 4c also exhibited a good safety profile at the cellular level. Preliminary mechanism study indicated that 4c might increase intracellular lipid metabolism by activating AMPK. These results provide a novel family of lead compounds for the discovery of anti-NAFLD candidates.
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To evaluate the efficacy and safety of Kuntai Capsules in the treatment of perimenopausal syndrome. Systematic reviews on Kuntai Capsules in the treatment of perimenopausal syndrome were retrieved from Chinese and English databases from database establishment to August 31, 2020. AMSTER-2 scale, GRADE scale and ROBIS tools were used respectively to evaluate the methodological quality, evidence quality level and bias risk of the finally included systematic reviews. A total of 6 systematic reviews with 28 outcome indicators were included. The results of AMSTER-2 methodological quality assessment showed that one of the six systematic reviews was of low quality, and the other five were of extremely low quality. GRADE scale showed that 28 clinical outcome indicators were evaluated, three of which were intermediate-level ones, and the rest were low-level or very low-level ones. Two evidences of the three intermediate evidences were total efficiency, and the other intermediate evidence was Kupperman score. ROBIS bias risk assessment showed all the included studies were of high risk. The results showed that, Kuntai Capsules were effective in the treatment of perimenopausal symptoms, such as hot flashes and sweating. The improvement of E_2 level was not as good as that in the menopause hormone therapy group, but the incidence of adverse reactions was lower than that in the menopause hormone therapy group. However, the quality of evidence needs to be improved due to the low quality of methodology and high risk of bias. It is suggested that systematic review and reasonable design should be carried out in the future, and attention should be paid to the registration of research schemes. In addition, the research reports shall be prepared according to PRISMA statement.
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Female , Humans , Drugs, Chinese Herbal , Hormone Replacement Therapy , Perimenopause , Syndrome , Systematic Reviews as TopicABSTRACT
Objective: To screen and analyze the mutations of MITF gene in two children of type Ⅱ Waardenburg syndrome (WS2) from different families in Yunnan,China,and to explore the possible molecular pathogenesis. Methods: With informed consent, medical history collection, physical examinations, audiological evaluation, and high resolution computer tomography (HRCT) scan of temporal bone were performed on the two WS2 probands and their family members. Genomic DNA was extracted from peripheral blood of all individuals. The coding regions including all exons, part of introns and promoters of MITF, PAX3, SOX10, SNAI2, END3, ENDRB, and KITLG genes were sequenced by high-throughput sequencing. According to the results of high-throughput sequencing, pathogenic mutations detected in the probands and their parents were verified by Sanger sequencing. Results: The proband 1 carried c.641_643delGAA mutation in the 7th exon of MITF gene, which was a frame-shift mutation resulting in an amino acid change of p.214delR. It was a de novo mutation as the parents of proband 1 showed no variation on this site. The proband 2 carried heterozygous loss of the large fragment ranging from exon 1 to exon 9 of MITF gene, which defected the function of MITF protein. Conclusion: Genetic examinations provide important evidence for diagnosis of Waardenburg syndrome. Heterozygous mutation c.641_643delGAA and heterozygous loss of the large fragment ranging from exon 1 to exon 9 of MITF gene might be the molecular pathogenesis of the two WS2 probands in this study.
Subject(s)
Child , Humans , Asian People/genetics , China , Mutation , Pedigree , SOXE Transcription Factors/genetics , Waardenburg Syndrome/geneticsABSTRACT
As a pleiotropic cytokine, interleukin-6 (IL-6) participates in many physiological activities in vivo. IL-6 plays an important role in the physiology and pathology of chronic inflammation, autoimmune diseases, tumors and other diseases through diverse mechanisms. At present, inhibitors targeting IL-6/IL-6R have been shown to improve treatments for some inflammatory diseases such as rheumatoid arthritis and systemic juvenile idiopathic arthritis. IL-6 binds to a specific receptor to activate the downstream JAK/STAT3 signaling pathway. However abnormally activated STAT3 often appears in various types of malignant tumors and participates in the occurrence and development of tumors. In addition, studies have shown that IL-6 is a key factor in the cytokine storm associated with COVID-19 patients. The physiological participation of IL-6/STAT3 pathway in complex diseases makes this pathway become a research hotspot for drug discovery. Therefore, we summarize the latest research progress of small molecular inhibitors on IL-6/STAT3 signaling pathway, in order to provide a reference for the development of IL-6/STAT3 related drug in the future.
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OBJECTIVE@#To evaluate and to compare dimensional alterations of hard and soft tissues in molar extraction sites with irregular deficiency of bone plates due to advanced periodontitis receiving two different procedures, namely the flapped and flapless techniques with Bio-Gide membrane covering the Bio-Oss material for ridge preservation.@*METHODS@#Twenty-three patients with 24 infected-molar extraction sites received ridge preservation procedure, the first consecutive 12 sites belonged to the flap group (a full thickness mucoperiosteal flap and primary soft tissue closure) and the following 12 sites belonged to the flapless group (minimal flap with a collagen sponge and a secondary soft tissue closure). Width of keratinized tissue was evaluated before tooth extraction and after 6-month healing. Parallel periapical radiographs were taken immediately and 6 months after extraction to evaluate vertical bone changes. The width of the ridge was measured in the center of the ridge at the time of tooth extraction and after 6 months at implant placement.@*RESULTS@#After 6 months, width of keratinized tissue decreased (1.6±1.5) mm in the flap group (P=0.004) when compared with (0.3±1.6) mm in the flapless group (P>0.05). Both groups showed increases in ridge height from the central aspect, (5.53±4.20) mm for flap group and (7.70±4.35) mm for flapless group. These differences between the groups were not statistically significant (P=0.226). The ridge widths were (9.5±2.2) mm for flap group and (9.3±1.0) mm for flapless group at the time of implant insertion, and no statistical significance was observed between the flap and flapless groups.@*CONCLUSION@#The study points out that both ridge preservation techniques were effective in increasing ridge height and minimizing ridge resorption after tooth extraction, and the ridge width allowed the placement of implants 6 months after ridge preservation. The flapless technique gave positive outcome in terms of the keratinized gingival width than that of the flap technique.
Subject(s)
Humans , Alveolar Process , Molar , Periodontitis , Tooth Extraction , Tooth SocketABSTRACT
Objective To observe the effects of different doses of sinomenine on toll-like receptor (TLR) 2, TLR4 and myeloid differentiation factor 88 (Myd88) in cartilage of rabbit knee osteoarthritis model; To discuss its mechanism of action. Methods Knee osteoarthritis model was established by Hulth method. Experimental rabbits were randomly divided into control group, model group, sinomenine low-, medium-and high-dose groups. Blank group received no processing. Model group, sinomenine low-, medium-and high-dose groups received intra-articular injection of normal saline and sinomenine 0.2 mL (5 mg), 0.35 mL (8.75 mg) and 0.5 mL (12.5 mg) respectively, for 10 times. Real-time fluorescence quantitative PCR and Western blot were used to detect m RNA and protein expressions of TLR2, TLR4 and My D88 in cartilage. Results m RNA and protein expressions of TLR2, TLR4 and MyD88 in model group significantly increased compared with control group (P<0.01); compared with model group, m RNA and protein expressions of TLR2, TLR4 and My D88 in sinomenine medium-and high-dose groups decreased significantly (P<0.05, P<0.01). Conclusion Sinomenine can inhibit the cartilage immune response of rabbit knee osteoarthritis by down-regulating expressions of key molecules in the TLR/My D88 pathway.
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Aim To investigate the effect of squalene on LDLR expression in HepG2 cells and its mechanism of down-regulated cholesterol. Methods The prolifer-ation of HepG2 cells exposed to squalene at different concentrations was measured by MTT assay. The effect of squalene on the expression of LDLR in HepG2 cells was measured by flow cytometry and fluorescence mi-croscopy. The effect of different concentrations of squa-lene on the interaction between SCAP and Insig2, two key protein molecules of SREBP pathway, was assayed by FRET technology. Results MTT results showed that squalene had inhibitory effect on the proliferation of HepG2 cells in a dose-dependent manner. Flow cy-tometry and fluorescence microscopy results showed that squalene enhanced LDLR expression in HepG2 cells compared with the control group. The results of FRET technology revealed that compared with model control group, the YFP fluorescence value in Squalene group dramatically declined, and the YFP fluorescence value of each drug group decreased with the range of 5~25 μmol·L-1 squalene concentration. Conclusions Squalene may promote the expression of LDLR in HepG2 cells through inhibiting the interaction between SCAP and Insig2 proteins in SREBP pathway, which may confirm that squalene is a potential novel drug for the down-regulation of cholesterol level.
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<p><b>OBJECTIVE</b>To explore the correlation between JAK/STAT signaling pathways and pathogenesis of immune thrombocytopenia(ITP).</p><p><b>METHODS</b>Twenty-six newly-diagnosed ITP patients was included in this study. They all meet the clinical and hematological criteria for the diagnosis of ITP, and patients with coronary heart disease, severe refractory hypertension, diabetes or with severe liver or kidney function incompetence were ruled out. 24 healthy control without autoimmune diseases, viral infectious diseases and with normal liver and kidney functions were also included. The expressions of Jak3, p-Jak3 mRNA, Stat3, and p-Stat3 were tested and the changes in levels of IL-21 mRNA, IL-21 cell secretion after DEX intervention and AG490 blockade were measured.</p><p><b>RESULTS</b>Compared with the healthy control, patients with ITP had significantly high expressions of Jak3, p-Jak3 mRNA, Stat3 and p-Stat3 protein, which significantly reduced after AG490 blocking (P<0.01). The expression of IL-21 mRNA and the secretion of IL-21 obviously decreased after DEX intervention, but increased after AG490 blocking(P<0.01).</p><p><b>CONCLUSION</b>The pathogenesis of ITP associates with the activation of JAK/STAT signaling pathways, and IL-21-mediated JAK/STAT signaling pathways play regulatory role in ITP.</p>
Subject(s)
Humans , Interleukins , Purpura, Thrombocytopenic, Idiopathic , STAT3 Transcription Factor , Signal TransductionABSTRACT
AIM: To research the correlation factor of the anterior segment values of eyes with different axial lengths.METHODS: In this study, 697 cases 697 eyes were included.According to axial length we divided all the cases into short axial length group, normal axial length group, mild long axial length group, moderate long axial length group and severe long axial length group.The relevant indicators of the anterior segment values of patients in the five groups was comparatively analyzed.RESULTS: In the short axial length group, the anterior chamber volume (ACV) showed a significantly negative correlation with age;anterior chamber depth (ACD) showed a significantly negative correlation with age.In the normal axial length group, the ACV showed a significantly negative correlation with age and a significantly positive correlation with axial length(AXL);the anterior chamber angle (ACA) showed a significantly negative correlation with age and a significantly positive correlation with AXL, and a significantly positive correlation with corneal curvature;the ACD showed a significantly negative correlation with age and a significantly positive correlation with AXL.In the mild long axial length group, the ACV showed a significantly negative correlation with age and a significantly positive correlation with AXL, and a significantly negative correlation with corneal curvature;the ACA showed a significantly negative correlation with age and a significantly positive correlation with AXL, and a significantly positive correlation with corneal curvature;the ACD showed a significantly negative correlation with age and a significantly positive correlation with AXL.In the moderate long axial length group, the ACV showed a significantly negative correlation with age;the ACA showed a significantly positive correlation with AXL;the ACD showed a significantly positive correlation with AXL.In the severe long axial length group, the ACV showed a significantly negative correlation with age.There were no significant differences on ACV, ACA and ACD among mild long axial length group, moderate long axial length group and severe long axial length group (P>0.05), while the difference between other groups was significant (P<0.05).CONCLUSION: There has a correlation between the anterior chamber values (ACV, ACA, ACD) age and AXL for eyes which AXL were 22-27mm, while the correlation would disappear as the AXL became shorter or longer.There was a significant growth trend of anterior chamber values for eyes with AXL <27mm.
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Our study was to investigate the epidemiological characteristics of M.tuberculosis from a national tuberculosis referral center in China. All strains isolated from TB patients, were genotyped by the RD105 deletion, 8 and 51 SNP loci and VNTR. The high differentiation SNPs of modern Beijing strains were analyzed for protein function and structure. 413 M. tuberculosis were included. Of 379 Beijing lineage M. tuberculosis, 'modern' and 'ancient' strains respectively represented 85.5% (324/379) and 14.5% (55/379). Rv2494 (V48A) and Rv0245 (S103F) were confirmed as high differentiation SNPs associated with modern strains. In a word, Modern Beijing lineage M.tuberculosis was dominant and the structural models suggested that modern sub-lineage may more easily survive in 'extreme' host condition.
Subject(s)
Humans , China , Epidemiology , DNA, Bacterial , Genetics , Genome, Bacterial , Hospitals, Chronic Disease , Molecular Epidemiology , Mycobacterium tuberculosis , Classification , Genetics , Phylogeny , Phylogeography , Polymorphism, Single Nucleotide , Tuberculosis , Epidemiology , MicrobiologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the epidemiological characteristics of measles cases of new genotype D8 in Beijing from January to June, 2013.</p><p><b>METHODS</b>Epidemiological survey and descriptive analysis was conducted.</p><p><b>RESULTS</b>661 suspected measles were reported from January to June, 2013. 416 were confirmed measles cases by serology and etiology detection. 28 measles cases were caused by genotype D8 measles virus by genotype identification. There were 2 measles outbreak including 14 cases and 14 sporadic cases. The incidence peak was during April and May. 25 cases (89.3%, 25/28) occurred in downtown and suburban districts. 22 cases (78.5%, 22/28) were adults aged 15-39 years and 19 cases (67.9%, 19/28) were migrant population. 12 cases (85.7%, 12/14) in outbreak were migrant population working in clothing sales. There was epidemiological association between 2 outbreaks.</p><p><b>CONCLUSION</b>Measles cases of genotype D8 were found for the first time in Beijing. Genotype D8 virus mainly infected migrant adults and caused local outbreak and endemic.</p>
Subject(s)
Adolescent , Adult , Female , Humans , Male , China , Epidemiology , Disease Outbreaks , Genotype , Incidence , Measles , Epidemiology , Virology , Measles virus , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To explore the clinical significance of hematocrit used as a predictor for diagnosis and evaluation of resuscitation effect in the early shock stage after burn.</p><p><b>METHODS</b>Clinical data of 131 severely burned patients admitted to our burn unit from January 2000 to December 2011 were retrospectively analyzed. The burn patients were divided into group A (n = 80) and group B (n = 51) based on the hematocrit level at post burn hour (PBH) 24. The hematocrit levels in group A were less than or equal to 0.50, which in group B were higher than 0.50. There were no statistically significant differences between two groups in age, gender, body weight, admission time after burn, total burn area, full-thickness burn area, and degree of inhalation injury (P values all above 0.05). Hematocrit levels in the shock stage were recorded. Total urine output, base excess, and the volume of fluid infused per kg per %TBSA at PBH 24 were recorded. Rates of complication and mortality were recorded. Data were processed with t test, chi-square test, and Wilcoxon rank sum test.</p><p><b>RESULTS</b>Hematocrit level of group A at PBH 24 was decreased to about 0.45, while that of group B was decreased to about 0.55. The urine output in group A at PBH 24 [(61 ± 22) mL/h] was higher than that in group B [(53 ± 20) mL/h, t = 2.212, P < 0.05]. Base excess in group A at PBH 24 [(-6.1 ± 2.9) mmol/L] was significantly higher than that in group B [(-9.0 ± 3.8) mmol/L, t = 4.888, P < 0.01]. The volume infused per kg per %TBSA was higher in group A [(1.9 ± 0.4) mL·kg(-1)·%TBSA(-1)] than in group B [(1.7 ± 0.4) mL·kg(-1)·%TBSA(-1), t = 2.472, P < 0.05]. The rates of complication and mortality in group A [11.3%(9/80), 8.8%(7/80), respectively] were significantly lower than those in group B [27.5%(14/51), 21.6%(11/51), with χ(2) values respectively 5.648 and 4.318, P values all below 0.05].</p><p><b>CONCLUSIONS</b>Hematocrit can indirectly reflect resuscitation effect in the burn shock stage. Whether hematocrit level can be lowered to 0.45-0.50 during the first 24 hours after burn may be an important index for evaluation of fluid resuscitation effect in the early shock stage after severe burn.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Burns , Blood , Therapeutics , Fluid Therapy , Hematocrit , Resuscitation , Retrospective Studies , Shock , Blood , TherapeuticsABSTRACT
<p><b>OBJECTIVE</b>To investigate the genetic association pattern between single-nucleotide polymorphisms (SNP) in the interleukin-1 receptor-associated kinase 4 (IRAK-4) gene and allergic rhinitis (AR).</p><p><b>METHODS</b>A population of 379 patients with the diagnosis of AR and 333 healthy controls who lived in Beijing region was recruited. A total of 8 reprehensive marker SNP which were in IRAK-4 gene region were selected according to the Beijing people database from Hapmap website. The individual genotyping was performed by MassARRAY platform. SPSS 13.0 software was used for statistic analysis.</p><p><b>RESULTS</b>Subgroup analysis for the presence of different allergen sensitivities displayed associations only in the house dust mite-allergic cohorts (rs3794262: P = 0.0034, OR = 1.7388; rs4251481: P = 0.0023, OR = 2.6593), but not in subjects who were allergic to pollens as well as mix allergens.</p><p><b>CONCLUSION</b>The potential genetic contribution of the IRAK-4 gene to AR demonstrated an allergen-dependant association pattern in Chinese population.</p>
Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young Adult , Allergens , Genetics , Allergy and Immunology , Asian People , Genetics , Case-Control Studies , Genetic Predisposition to Disease , Genotype , Interleukin-1 Receptor-Associated Kinases , Genetics , Allergy and Immunology , Polymorphism, Single Nucleotide , Rhinitis, Allergic, Perennial , Genetics , Allergy and Immunology , Rhinitis, Allergic, Seasonal , Genetics , Allergy and ImmunologyABSTRACT
<p><b>OBJECTIVE</b>To investigate whether the single nucleotide polymorphisms (SNP) in the FCER1A gene are associated with serum total IgE level in Chinese allergic rhinitis (AR) cohort.</p><p><b>METHODS</b>A total of 378 patients diagnosed as AR was included in this study. Serum total IgE level was detected by UniCAP100 testing system. A total of 8 representativeness marker SNP which were in FCER1A gene region were selected according to the Beijing people database from Hapmap website and the running results of Haploview 4.1 software. The individual genotyping was performed by MassARRAY platform.</p><p><b>RESULTS</b>Three hundred and seventy-eight individuals (227 males and 151 females) with AR were prospectively recruited. The median of the total serum IgE measurements for the study population were 150 kU/L and ranged from 6.94 kU/L to 5000 kU/L. Levene tests showed the homogeneity of variance of total IgE level among different genotypes regarding each SNP locus. ANOVA tests demonstrated that none of the selected polymorphism loci in FCER1A was associated with total IgE level.</p><p><b>CONCLUSION</b>Present study failed to find an association between SNP in the FCER1A gene region and serum total IgE level in Chinese AR.</p>
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young Adult , Immunoglobulin E , Blood , Polymorphism, Single Nucleotide , Receptors, IgE , Genetics , Rhinitis, Allergic, Perennial , Blood , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effect of CYP11B2 gene -344T/C polymorphism on renin-angiotensin-aldosterone system (RAAS) activity and blood pressure in response to hydrochlorothiazide (HCTZ) treatment in Han Chinese patients with essential hypertension.</p><p><b>METHODS</b>Eight hundred and twenty-nine patients with mild/moderate essential hypertensive were enrolled. All subjects had their antihypertensive medications withdrawn. After two weeks of wash-out period with placebo, each patient was given 12.5 mg of HCTZ per day for the next six weeks. Physical, biochemical measurements, and the activity of RAAS were taken at the end of the wash-out period (baseline) and 6-week diuretic therapy period. Changes in systolic and diastolic blood pressure were analyzed for association with interaction between genotypes at CYP11B2 -344T/C polymorphism and gender.</p><p><b>RESULTS</b>A total of 776 patients completed the study. 17.5% of subjects have achieved blood pressure normalization after six weeks treatment. For male patients, the aldosterone level with CC genotype was significantly higher than that of those with TT or TC genotype. Following the HCTZ treatment, the blood pressure response in patients with CC genotype was less obvious than that in others, whilst the increase of aldosterone level was greater. For female patients, no association was found between CYP11B2 -344T/C polymorphism and aldosterone level. Following the HCTZ treatment, the blood pressure response in patients with CC genotype was greater than others, whilst the increase of aldosterone activity was less apparent.</p><p><b>CONCLUSION</b>In males, the -344T/C polymorphism of CYP11B2 gene is associated with aldosterone level, and the change of aldosterone level was greater, the blood pressure response was weaker after HCTZ treatment. In females, there was no association between this polymorphism and aldosterone level. The change of aldosterone level and blood pressure response to HCTZ were different from that in males.</p>
Subject(s)
Female , Humans , Male , Middle Aged , Antihypertensive Agents , Pharmacology , Blood Pressure , Genetics , Cytochrome P-450 CYP11B2 , Genetics , Hydrochlorothiazide , Pharmacology , Hypertension , Drug Therapy , Genetics , Polymorphism, Genetic , Renin-Angiotensin System , GeneticsABSTRACT
Secreted protein, acidic and rich in cysteine (SPARC) is expressed in numerous types of tumors and is suggested to have prognostic value. Moreover, because of its strong affinity for albumin, and hence albumin-bound drugs, SPARC has increasingly become a focus for research. In this study, we aimed to determine SPARC expression in patients with non-small cell lung cancer (NSCLC) and investigate the association of SPARC with disease prognosis. Tissue microarrays were constructed with specimens from 105 patients with NSCLC treated at Sun Yat-sen University Cancer Center, and immunohistochemical analysis was performed on these tissue microarrays to assess SPARC expression. Our results showed that SPARC expression status did not significantly relate with age, gender, and tumor stage. However, SPARC was expressed more frequently in squamous cell carcinoma than in adenocarcinoma (75% vs. 43.5%, P = 0.004). Patients with smoking history had higher SPARC expression than non-smokers (68.2% vs. 33.3%, P = 0.002). In both univariate and multivariate analyses, SPARC was a prognostic factor of overall survival (HR = 0.32; 95% CI: 0.16-0.65) but not disease-free survival. Our study indicates that SPARC expression is higher in squamous cell carcinoma than in adenocarcinoma in NSCLC. Most notably, SPARC can be used as a prognostic factor for NSCLC.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Adenocarcinoma , Metabolism , Pathology , Carcinoma, Non-Small-Cell Lung , Metabolism , Pathology , Carcinoma, Squamous Cell , Metabolism , Pathology , Disease-Free Survival , Immunohistochemistry , Lung Neoplasms , Metabolism , Pathology , Neoplasm Staging , Osteonectin , Metabolism , Proportional Hazards Models , Smoking , Survival RateABSTRACT
Gemcitabine has high activity against nasopharyngeal carcinoma (NPC). The level of ribonucleotide reductase subunit M1 (RRM1) expression is closely related to the efficacy of gemcitabine on non-small cell lung cancer and pancreatic cancer. However, the expression of RRM1 and its association with sensitivity to gemcitabine-based chemotherapy in advanced NPC is not known. In this study, we retrospectively collected 48 formalin-fixed, paraffin-embedded NPC tissues to evaluate the expression of RRM1 using immunohistochemistry. All patients were diagnosed and treated with gemcitabine-based chemotherapy at Sun Yat-sen University Cancer Center. RRM1 expression was positive in 17(35%) patients. RRM1 expression was not associated with sex, age, performance status, WHO histological type, number of distant metastases, previous treatment, or cycles of gemcitabine-based chemotherapy(P> 0.05). The progression-free survival of the RRM1-positive group was shorter than that of the RRM1-negative group (5 months vs. 7 months, P = 0.036), and the response rate of the RRM1-positive group was somewhat lower than that of the RRM1-negative group (51.6% vs. 35.3%, P = 0.278). There was no significant difference in median survival between the RRM1-positive and RRM1-negative groups (22 months vs. 19 months, P = 0.540). Our results show that RRM1-negative expression is related with longer progression-free survival in advanced NPC patients treated with gemcitabine-based regimens.