The hypertension is one of chronic vascular diseases, which often implicates multiple tissues causing stroke, cardiac hypertrophy, and renal failure. A growing body of evidence suggests that inflammatory mechanisms are important participants in the pathophysiology of hypertension. In this study, the inflammatory status of these tissues (kidney, liver, heart, and brain) in spontaneously hypertensive rats (SHR) was analyzed and its molecular mechanism was explored. The tissues were dissected from SHR and age-matched control Wistar-Kyoto (WKY) rats to investigate the abundance of inflammation-related mediators (IL-1beta, TNFalpha, ICAM-1, iNOS, C/EBPdelta and PPARgamma). mRNA levels were determined by reverse transcription-polymerase chain reaction and protein expression was evaluated by Western blot. To evaluate the oxidative stress of tissues, carbonyl protein content and total antioxidant capacity of tissues were detected by spectrophotometry and ferric reduction ability power (FRAP) method. The results suggest that: (1) Expressions of inflammation-related mediators (IL-1beta, TNFalpha, ICAM-1, iNOS, C/EBPdelta and PPARgamma) in SHR were higher compared with those in WKY rats except no evident increase of IL-1beta mRNA in liver and brain in SHR. (2) Tissues in SHR contained obviously increased carbonyl protein (nmol/mg protein) compared to that in WKY rats (8.93+/-1.08 vs 2.27+/-0.43 for kidney, 2.23+/-0.23 vs 0.17+/-0.02 for heart, 13.42+/-1.10 vs 5.72+/-1.01 for brain, respectively, P<0.05). However, no evident difference in the amount of carbonyl protein in liver was detected between SHR and WKY rats. (3) Total antioxidant capacities of kidney, liver, heart and brain were markedly lower in SHR than that in WKY rats (P<0.05). Thus, the present data reveal a higher inflammatory status in the important tissues in SHR and indicate that inflammation might play a potential role in pathogenesis of hypertension and secondary organ complications.
Animals ; Brain ; metabolism ; pathology ; Cytokines ; genetics ; metabolism ; Hypertension ; pathology ; Inflammation ; pathology ; Interleukin-1beta ; genetics ; metabolism ; Kidney ; metabolism ; pathology ; Male ; Myocardium ; metabolism ; pathology ; Oxidative Stress ; immunology ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

OBJECTIVETo study the expression of NFkappaB p65 and its target genes in intestinal metaplasia (IM), dysplasia (Dys), gastric cancer (GC) infected with Helicobacter pylori (Hp) and explore the mechanism of infection by cytotoxin-associated antigen A expressing Hp (CagA(+)Hp) in the development of gastric cancer.

METHODSCagA antibody in blood sample of 289 patients was determined by ELISA. Hp was detected by rapid urease test and Warthin starry staining. Expression of NFkappaB p65 and its target genes in IM, Dys and GC was examined by immunohistochemistry.

RESULTSIn IMI approximately II, IMIII, DysI, DysII approximately III and GC, the expression of NFkappaB p65 was significantly higher in patients with CagA(+)Hp infection than those without CagA Hp infection. In IMIII and DysII approximately III, the expression of NFkappaB p65, c-myc, CyclinD(1) and bcl-xl was significantly higher in patients with CagA Hp infection than those without CagA Hp infection. In gastric cancer infected with CagA(+)Hp, the expression of NFkappaB p65, c-myc, CyclinD(1) and bcl-xl was significantly higher in intestinal type than in diffuse type.

CONCLUSIONThere are different mechanisms in intestinal type and diffuse type in the development of gastric cancer. The occurrence of intestinal type gastric cancer is associated with CagA(+)Hp infection which by NFkappaB p65 upregulating the expression of c-myc, CyclinD(1),bcl-xl in patients with IMIII, DysII approximately III. It may be an effective method to prevent gastric cancer by inhibiting NFkappaB p65.

Adult ; Aged ; Antigens, Bacterial ; analysis ; Bacterial Proteins ; analysis ; Cyclin D1 ; metabolism ; Female ; Helicobacter Infections ; complications ; metabolism ; microbiology ; Helicobacter pylori ; Humans ; Male ; Middle Aged ; Precancerous Conditions ; metabolism ; microbiology ; pathology ; Proto-Oncogene Proteins c-myc ; metabolism ; Stomach Neoplasms ; metabolism ; microbiology ; pathology ; Transcription Factor RelA ; genetics ; metabolism ; bcl-X Protein ; metabolism

Adult ; Aged ; Chylothorax ; etiology ; therapy ; Female ; Humans ; Middle Aged ; Neck Dissection ; adverse effects ; Retrospective Studies ; Thyroid Neoplasms ; surgery

BACKGROUNDThe chronic pathological changes in vascular walls of hypertension may exert destructive effects on multiple organ systems. Accumulating evidence indicates that inflammatory reactions are involved in the pathological changes of hypertension. Three peroxisome proliferator-activated receptors (PPARs) have been identified: PPARalpha, PPARbeta/delta, and PPARgamma, all of which have multiple biological effects, especially the inhibition of inflammation. The aim of this study was to evaluate PPAR isoforms expression profile in important organs of spontaneously hypertensive rats (SHR) and to understand the modulation of endogenous PPAR isoforms under inflammatory condition.

METHODSTissues (kidney, liver, heart, and brain) were dissected from SHR and age-matched control Wistar-Kyoto rats (WKY) to investigate the abundance of PPAR isoforms and PPAR-responsive genes (acyl-CoA oxidase and CD36). The expression of CCAAT/enhancer-binding protein delta (C/EBPdelta), which can trans-activate PPARgamma expression, was also observed. The inflammatory response was analyzed by the expression of inflammatory mediators inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, interleukin-1 beta (IL-1beta), and tumor necrosis factor alpha (TNFalpha), and formation of carbonyl and nitrated proteins.

RESULTSThe expressions of 3 PPAR isoforms and PPAR-responsive genes were markedly upregulated in SHR compared with those of WKY. Specifically, the expression of PPARalpha protein in the kidney, liver, heart and brain increased by 130.76%, 91.48%, 306.24%, and 90.70%; PPARbeta/delta upregulated by 109.34%, 161.98%, 137.04%, and 131.66%; PPARgamma increased by 393.76%, 193.17%, 559.29%, and 591.18%. In consistent with the changes in PPARgamma, the expression of C/EBPdelta was also dramatically elevated in SHR. Inflammatory mediators expressions were significantly increased in the most organs of SHR than WKY. As a consequence, increased formation of carbonyl and nitrated proteins were also observed in the most organs of SHR.

CONCLUSIONSThese findings suggest an enhanced inflammatory response in the organs of SHR, which might play a key role in pathogenesis of hypertension and secondary organ complications. Changes (increases) in PPARs expression may reflect a compensatory mechanism to the inflammatory status of hypertensive rats.

Animals ; Blood Pressure ; Blotting, Western ; E-Selectin ; genetics ; metabolism ; Gene Expression ; Hypertension ; genetics ; metabolism ; physiopathology ; Inflammation ; genetics ; metabolism ; physiopathology ; Interleukin-1beta ; genetics ; metabolism ; Male ; PPAR alpha ; genetics ; metabolism ; PPAR delta ; genetics ; metabolism ; PPAR gamma ; genetics ; metabolism ; Peroxisome Proliferator-Activated Receptors ; genetics ; metabolism ; Plethysmography ; methods ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Necrosis Factor-alpha ; genetics ; metabolism ; Vascular Cell Adhesion Molecule-1 ; genetics ; metabolism

Objective To provide scientific evidences for improving children early integrated development,through analyzing the mental developmental status and characteristics of 322 cases of 2-year-old children in Nanjing.Methods Intelligence and motor development condition in 322 cases of 2-year-old children were assessed by using Bayley Scales of Infant Development test,and the assessed results were analyzed.Results 1.The incidences of the children whose mental development index(MDI)or psychomotor development index(PDI)were under 69 were 3.1% and 5.6%,respectively;2.The MDI mean score(114.34?19.65)was significantly higher than that of PDI(101.73?21.53)(t=9.71,P0.05).Conclusions The incidences of mental retardation in this study were consistent with the result reported by World Health Organization.There were differences between motor and intelligence development in children,as well as the intelligence development between male and female.Therefore,it should be implemented early childhood developmental screening in child health care.Parents should be given scientific guides about intelligence and motor development of children.

OBJECTIVE: To study the association between maternal alcohol consumption and the risk of congenital heart disease (CHD) in offspring. METHODS: PubMed, Cochrane Library, Web of Science, Google Scholar, China Biology Medicine disc, Wanfang Database, CNKI Database, and Weipu Database were searched for the articles on the association between maternal alcohol consumption and congenital heart disease in offspring. These articles were published up to November 30, 2019. A random effects model or a fixed effects model was used for the pooled analysis of the results of each study, and then the pooled effective value and its 95%CI were calculated. A subgroup analysis was performed to explore heterogeneous regulators. Funnel plots and an Egger's test were used to assess publication bias. RESULTS: A total of 4 409 articles were searched, and 55 articles were finally included in this analysis, among which there were 6 cohort studies and 49 case-control studies. The Meta analysis showed heterogeneity across all studies (I=74%, P<0.01). The random effects model showed that maternal alcohol consumption was associated with CHD in offspring, with an OR of 1.18 (95%CI: 1.09-1.28). The Egger's test showed a certain degree of publication bias (P<0.05), and after adjustment, the pooled OR of CHD in offspring was 1.10 (95%CI: 1.01-1.21). CONCLUSIONS Maternal alcohol consumption may increase the risk of CHD in offspring.
Alcohol Drinking ; Case-Control Studies ; China ; Cohort Studies ; Heart Defects, Congenital ; Humans ; Risk Factors

BACKGROUNDAnkylosing spondylitis (AS) is a common inflammatory rheumatic disease which lacks satisfactory treatment so far. Sinomenine (SIN) is an alkaloid and has recently been utilized in treating multiple rheumatic diseases including AS in China, but its exact mechanism remains to be explored. This study investigated the alteration of proteome in peripheral blood mononuclear cells (PBMCs) from AS patients.

METHODSThirty AS patients were enrolled in this study. PBMCs from each AS patient were cultured in medium with or without SIN respectively. Then PBMCs proteins from both groups were separated by two-dimensional electrophoresis (2-DE) and analyzed by mass spectrometry (MS). Two differentially expressed proteins were then chosen to be verified using Western blotting.

RESULTSSeven proteins, including a-synuclein (SNCA), calmodulin (CALM), acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A), chloride intracellular channel protein 1 (CLIC1), guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (GNB1), gelsolin (GSN) and histone H2B type 1-M (HISTH2BM) were over-expressed, while coronin- 1A (CORO1A) was under-expressed in the SIN-treated PBMCs. Further bioinformatics search indicated that the changes of SNCA, ANP32A and CLIC1 pertained to apoptosis, while changes of GSN and CORO1A were associated with both apoptosis and inhibition of immunological function. Subsequently GSN and CORO1A were selected to validate by Western blotting and the results were consistent with those of 2-DE.

CONCLUSIONThere were 8 differentially expressed proteins in the SIN-treated PBMCs, which might shed some light on the mechanism of SIN in the treatment of AS.

Adolescent ; Adult ; Blood Proteins ; analysis ; Blotting, Western ; Cells, Cultured ; Electrophoresis, Gel, Two-Dimensional ; Female ; Humans ; Leukocytes, Mononuclear ; chemistry ; Male ; Middle Aged ; Morphinans ; pharmacology ; Proteomics ; methods ; Reproducibility of Results ; Spondylitis, Ankylosing ; blood

The p53 signaling pathway works as a potent barrier to tumor progression. Two single nucleotide polymorphisms (SNPs) in the gene loci of p53 pathway, p53 codon 72 Arg72Pro and MDM2 SNP309 (T > G), have been shown to cause perturbation of p53 function, but the effect of the two SNPs on the risk of hepatocellular carcinoma (HCC) remains inconsistent. This study investigated the influence of combined p53 Arg72Pro and MDM2 SNP309 on the risk of developing HCC in patients with chronic hepatitis B virus infection, and evaluated the significance of the two combined SNPs on patient prognosis. In total, 350 HCC patients, 230 non-HCC patients, and 96 healthy controls were genotyped for the p53 Arg72Pro and MDM2 SNP309. The combined p53 Pro/Pro and MDM2 G/G genotype was significantly associated with HCC risk (P = 0.047). Multivariate analysis indicated that combined p53 Pro/Pro and MDM2 G/G genotype was an independent factor affecting recurrence and survival (P < 0.05). Patients with combined p53 Pro/Pro and MDM2 G/G genotypes had a poorer prognosis than other genotypes, P < 0.01 for both disease-free survival (DFS) and overall survival (OS). DFS and OS rates also differed significantly between Barcelona Clinic Liver Cancer (BCLC) stage A patients with combined p53 Pro/Pro and MDM2 G/G and other genotypes (P < 0.05). Thus, the combined p53 Pro/Pro and MDM2 G/G genotype is associated with increased risk of developing HCC and is an independent adverse prognostic indicator in early stage HCC.
Carcinoma, Hepatocellular ; diagnosis ; genetics ; surgery ; virology ; Carrier State ; virology ; Cohort Studies ; Female ; Genetic Predisposition to Disease ; genetics ; Hepatitis B virus ; physiology ; Humans ; Liver Neoplasms ; diagnosis ; genetics ; surgery ; virology ; Male ; Middle Aged ; Neoplasm Staging ; Polymorphism, Single Nucleotide ; Prognosis ; Proto-Oncogene Proteins c-mdm2 ; genetics ; Tumor Suppressor Protein p53 ; genetics

OBJECTIVE: To observe the effect of high positive acceleration (+Gz) environment on dental implant osseointegration in a rabbit model and to investigate its mechanism. METHODS: Forty-eight New Zealand white rabbits were randomly divided into 6 groups. The rabbit's mandibular incisors were extracted and 1 implant was placed in each socket immediately. After 1 week of rest, the rabbits were exposed to a high +Gz environment, 3 times a week. The rabbits were sacrificed at 3 weeks (2 weeks +Gz exposure), 5 weeks (4 weeks +Gz exposure), and 12 weeks (4 weeks +Gz exposure and 7 weeks normal environment) after surgery, respectively. Specimens were harvested for micro-CT scanning, histological analysis, and real-time polymerase chain reaction examination. RESULTS: Compared with those in the control group, the mRNA expression levels of bone morphogenetic protein-2 (BMP-2), osteopontin (OPN), and transforming growth factor-β1 (TGF-β1) were significantly lower (P < 0.05), while the mRNA expression level of receptor activator of nuclear factor κB ligand (RANKL) and the RANKL/osteoprotegerin (OPG) ratio were significantly higher (P < 0.05) at 3 weeks; values of bone volume fraction, trabecular number, bone-implant contact (BIC), and TGF-β1 and OPG mRNA expression levels were significantly lower (P < 0.05), and the value of trabecular separation, RANKL mRNA expression level and RANKL/OPG ratio were significantly higher (P < 0.05) at 5 weeks; and the value of BIC was still significantly lower (P < 0.05) at 12 weeks in the experimental group. CONCLUSION Early exposure to the high +Gz environment after implant surgery might have an adverse effect on osseointegration, and its mechanism could be related to the inhibition of osteoblast activity and promotion of osteoclast activity.

Objective: To study the changes in the permeability of the blood labyrinth barrier of the aging cochlea in mice, and to establish a non-contact co-culture model of endothelial cells (EC) and pericytes (PC) to furtherly investigate the cochlear stria vascularis microvascular pericytes impact on the permeability of endothelial cells. Methods: C57BL/6J mice were divided into two groups, three months old as young group, 12 months old as senile group. Cell experiment was divided into four groups, EC group, EC+PC co-culture group, D-gal+EC group and D-gal+EC+PC co-culture group. Auditory brainstem response (auditory brain response, ABR) was used to detect the auditory function of the two groups of mice. Evans blue staining was applied to detect the permeability of the cochlear blood labyrinth barrier of the two groups of mice. Transmission electron microscopy was used to observe the ultrastructure of blood labyrinth barrier endothelial cells, pericytes and tight junctions in the two groups of mice. Immunohistochemistry was used to detect the expression levels of tight junction proteins in the stria vascularis of the cochlea of the two groups of mice. Transwell chamber was used to detect the permeability of endothelial cells. Western blot and immunofluorescence technology were used to detect the expression level of tight junction protein on endothelial cells. SPSS 20.0 software was used to analyze the data. Results: Compared with the young group, the ABR threshold of the aging group was significantly increased, the latency of wave I was prolonged (t=10.25, P<0.01;t=5.61, P<0.05), the permeability of the cochlear blood labyrinth barrier was increased and the expression of tight junction protein on the vascular stria was decreased (P<0.05). The cochlear ultrastructure showed that the cochlear vascular stria microvascular lumen was deformed, the basement membrane thickened and the tight junction gap between endothelium enlarged. The positive rate of ECs and PCs in primary culture was more than 95%. The cells induced by 15 g/L D-gal were determined to be senescent cells. Compared with EC group, the expression of tight junction protein in endothelial cells of D-gal+EC group decreased（t=7.42，P<0.01；t=13.19，P<0.05）and the permeability increased (t=11.17, P<0.01). In the co-culture group, the expression of tight junction protein between endothelial cells in EC+PC co-culture group and D-gal+EC+PC co-culture group increased and the permeability decreased. Conclusions: In aging mice, the permeability of cochlear blood labyrinth barrier will increase and the level of tight junction protein will decrease; in aging state, cochlear vascular stria microvascular pericytes may affect endothelial cell permeability by regulating the expression of tight junction protein.
Animals ; Cochlea ; Endothelial Cells ; Mice ; Mice, Inbred C57BL ; Pericytes ; Permeability ; Stria Vascularis ; Tight Junctions