Prevalence of fimA genotypes of Porphyromonas gingivalis and periodontal health status in Chinese adults

Background and Objective:  Porphyromonas gingivalis fimbriae play a key role in colonization of the oral cavity. The fimA gene, which encodes fimbrillin ( FimA ), can be classified into six types (I–V and Ib) according to nucleotide sequence. In the present study, we investigated the relationship between the prevalence of P. gingivalis -specific fimA genotypes and periodontal health status in Chinese adults.
Material and Methods:  One-hundred and fifteen patients with chronic periodontitis and 136 periodontally healthy adults were selected. P. gingivalis detection, determination of fimA genotypes, and the co-existence of Actinobacillus actinomycetemcomitans and Tannerella forsythia with various fimA types, were assessed by the polymerase chain reaction. Odds ratios and 95% confidence intervals were calculated for associating the fimA -specific genes with periodontitis.
Results:  P. gingivalis was detected in 22.1% of healthy subjects and in 81.7% of the patients. A single fimA genotype was detected in most samples. In healthy adults, the most prevalent fimA genotype was type I (66.7%). However, type II was detected most frequently (43.6%) in the patient group, followed by type IV (30.9%). The frequency of co-existing A. actinomycetemcomitans and T. forsythia was highest in type II fimA -positive sites. Statistical analysis revealed that periodontitis was associated with occurrences of type I (odds ratio 0.97), Ib (odds ratio 13.26), II (odds ratio 36.62), III (odds ratio 4.57), IV (odds ratio 22.86) and V (odds ratio 1.19).
Conclusion:  P. gingivalis type II followed by type IV were considered as disease-associated strains that account for the pathogenesis of chronic periodontitis in Chinese adults.     

Long-term outcomes of concurrent chemoradiotherapy versus radiotherapy alone in stage II nasopharyngeal carcinoma treated with IMRT: a retrospective study

Tumor Biology - This study aimed to evaluate the efficacy of concurrent chemoradiotherapy (CCRT) for stage II nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiation...     

The dual actions of Sanmiao wan as a hypouricemic agent: Down-regulation of hepatic XOD and renal mURAT1 in hyperuricemic mice

Ethnopharmacological relevance

Sanmiao wan (SMW) is widely used for the treatment of gout and hyperuricemia in traditional Chinese medicine.

Aim of the study

The aim of the present study was to investigate the hypouricemic effects of SMW and its possible mechanism in potassium oxonate-induced hyperuricemic mice.

Materials and methods

SMW at 489, 978 and 1956 mg/kg was orally administered to hyperuricemic and normal mice, and standard drug allopurinol (2.5 mg/kg) was served as a positive control. The effects of SMW on serum, urine and liver levels of uric acid, serum levels of creatinine, and activity of hepatic xanthine oxidase (XOD) were measured in mice. Moreover, the effects of SMW on the mRNA and protein levels of hepatic XOD and renal urate transporter 1 (mURAT1) in mice were analyzed by semi-quantitative RT-PCR and Western blotting methods, respectively.

Results

SMW significantly reduced uric acid levels in serum and liver, inhibited hepatic XOD activity, mRNA and protein levels in hyperuricemic mice. Furthermore, SMW could effectively down-regulate renal mURAT1 mRNA and protein levels of hyperuricemic mice. And it reversed oxonate-induced elevation in serum creatinine levels of mice. However, SMW did not show any effects in normal mice.

Conclusion

These findings suggested that SMW produced dual hypouricemic actions by suppressing hepatic XOD to reduce uric acid production and down-regulating renal mURAT1 to decrease urate reabsorption and enhance urate excretion in hyperuricemic mice.     

HDAC5, negatively regulated by miR‐148a‐3p,promotes colon cancer cell migration

Histone deacetylases (HDACs) are involved in many processes including tumor cell growth and proliferation and regulation of gene expression. To clarify the role of class IIa HDACs in the metastasis of colon adenocarcinoma, we used the class IIa HDAC inhibitor TMP269 and found that it effectively inhibited the migration ability of colon adenocarcinoma cells. Next, we silenced the member of class IIa HDACs and confirmed that the migratory ability of colon adenocarcinoma cells was significantly inhibited by silencing HDAC5 or HDAC7. HDAC5 plays a variety of roles in human cancers. Here, we examined the role of HDAC5 in colon adenocarcinoma. The results indicated that HDAC5 was highly expressed in tumor tissues and negatively correlated with the expression of miR‐148a‐3p. Moreover, the expression of HDAC5 was correlated with tumor progression. HDAC5 markedly increased the invasion and migration of cancer cells in vitro, an effect that could be inhibited by overexpression of miR‐148a‐3p. Following an intraperitoneal injection of colon adenocarcinoma cells in athymic nude mice, HDAC5 promoted tumor implant. Together, these findings showed that HDAC5 overexpression in colon adenocarcinoma is consistent with tumor progression and tumor cell migration and the impact of HDAC5 overexpression is reduced by miR‐148a‐3p.     

Differences of larval development and pathological changes in permissive and nonpermissive rodent hosts for Angiostrongylus cantonensis infection

Angiostrongylus cantonensis is a neurotrophic and pulmonary parasite which causes severe neuropathological damages by invading and developing in the central nervous system (CNS). Nonpermissive host with A. cantonensis infection appeared to have more serious neurologic symptoms, and there is still not much knowledge about the host-parasite interrelationship in different hosts. We investigated and compared the larval size, recovery rate, distribution, and the severity of pathologic injuries in the CNS of both permissive host (e.g., rats) and nonpermissive hosts (e.g., mice). In present study, mice infected with A. cantonensis showed higher worm recovery rate in late-stage infection and smaller size of intracranial larvae as compared to the infected rats. Intracranial larvae mainly aggregated on cerebral surface of infected rats but on surface of cerebellum and brainstem in mice. Hemorrhage and tissue edema on brain surface caused by worm migration appeared earlier and severer in infected mice than in rats. Neuropathological examination revealed that injuries induced by A. cantonensis in brain parenchyma included hemorrhage, vascular dilatation, focal necrosis with neuronal loss, and infiltration of inflammatory cells. In the comparison of these pathological changes in rats and mice, infected mice suffered more serious injuries and provoked more intense inflammatory response as compared to infected rats. All these morphological evidences indicate that larval development was retardant in the CNS of nonpermissive host, and nonpermissive host experienced more serious pathological injuries than permissive host. It implies that the difference in innate immune response to parasite infection attribute to host specificity.     

Applied research on serum protein fingerprints for prediction of Qi deficiency syndrome and phlegm and blood stasis in patients with non-small cell lung cancer

Objective

This study screened serum tumor biomarkers by surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to establish a subset which could be used for the prediction of Qi deficiency syndrome and phlegm and blood stasis in patients with non-small cell lung cancer; and as diagnostic model of Chinese medicine.

Methods

Serum samples from 63 lung cancer patients with Qi deficiency syndrome and phlegm and blood stasis, and 28 lung cancer patients with non-Qi deficiency syndrome and phlegm and blood stasis were analyzed using SELDI-TOF-MS with a PBS II-C protein chip reader. Protein profiles were generated using immobilized metal affinity capture (IMAC3) protein chips. Differentially-expressed proteins were screened. Protein peak clustering and classification analyses were performed using Biomarker Wizard and Biomarker Pattern software packages, respectively.

Results

A total of 268 effective protein peaks were detected in the 1,000–10,000 Da molecular range for the 15 serum proteins screened (P<0.05). The decision tree model was M 2284.97, with a sensitivity of 96.2% and a specificity of 66.7%.

Conclusion

SELDI-TOF-MS techniques, combined with a decision tree model, can help identify serum proteomic biomarkers related to Qi deficiency syndrome and phlegm and blood stasis in lung cancer patients; and the predictive model can be used to discriminate between Chinese medicine diagnostic models of disease.     

Replication and cumulative effects of GWAS-identified genetic variations for prostate cancer in Asians: a case-control study in the ChinaPCa consortium

A recent genome-wide association study has identified five new genetic variants for prostate cancer susceptibility in a Japanese population, but it is unknown whether these newly identified variants are associated with prostate cancer risk in other populations, including Chinese men. We genotyped these five variants in a case-control study of 1524 patients diagnosed with prostate cancer and 2169 control subjects from the Chinese Consortium for Prostate Cancer Genetics (ChinaPCa). We found that three of the five genetic variants were associated with prostate cancer risk (P = 4.33 × 10(-8) for rs12653946 at 5p15, 4.43 × 10(-5) for rs339331 at 6q22 and 8.42 × 10(-4) for rs9600079 at 13q22, respectively). A cumulative effect was observed in a dose-dependent manner with increasing numbers of risk variant alleles (P(trend) = 2.58 × 10(-13)), and men with 5-6 risk alleles had a 2-fold higher risk of prostate cancer than men with 0-2 risk alleles (odds ratio = 2.26, 95% confidence interval = 1.78-2.87). Furthermore, rs339331 T allele was significantly associated with RFX6 and GPRC6A higher messenger RNA expression, compared with the C allele. However, none of the variants was associated with clinical stage, Gleason score or family history. These results provide further evidence that the risk loci identified in Japanese men also contribute to prostate cancer susceptibility in Chinese men.     

A comparison of isolated circulating tumor cells and tissue biopsies using whole-genome sequencing in prostate cancer

Previous studies have demonstrated focal but limited molecular similarities between circulating tumor cells (CTCs) and biopsies using isolated genetic assays. We hypothesized that molecular similarity between CTCs and tissue exists at the single cell level when characterized by whole genome sequencing (WGS). By combining the NanoVelcro CTC Chip with laser capture microdissection (LCM), we developed a platform for single-CTC WGS. We performed this procedure on CTCs and tissue samples from a patient with advanced prostate cancer who had serial biopsies over the course of his clinical history. We achieved 30X depth and ≥ 95% coverage. Twenty-nine percent of the somatic single nucleotide variations (SSNVs) identified were founder mutations that were also identified in CTCs. In addition, 86% of the clonal mutations identified in CTCs could be traced back to either the primary or metastatic tumors. In this patient, we identified structural variations (SVs) including an intrachromosomal rearrangement in chr3 and an interchromosomal rearrangement between chr13 and chr15. These rearrangements were shared between tumor tissues and CTCs. At the same time, highly heterogeneous short structural variants were discovered in PTEN, RB1, and BRCA2 in all tumor and CTC samples. Using high-quality WGS on single-CTCs, we identified the shared genomic alterations between CTCs and tumor tissues. This approach yielded insight into the heterogeneity of the mutational landscape of SSNVs and SVs. It may be possible to use this approach to study heterogeneity and characterize the biological evolution of a cancer during the course of its natural history.