Prognostic Value of Overexpressed p16INK4a in Vulvar Cancer: A Meta-Analysis

Objective

This study aimed to examine the prognostic value of overexpressed p16^INK4a in vulvar cancer. Although the tumor suppressor p16^INK4a has been shown to be of prognostic value in a wide variety of cancers and precancerous lesions, its role in the vulvar cancer is still unclear.

Methods

All publications in English language on the association between p16^INK4a and clinicopathological features of vulvar cancer were searched from Pubmed, Embase, and Web of Science, and those in Chinese language were identified manually and online from the China National Knowledge Infrastructure. Strict inclusion and exclusion criteria were followed. Odds ratios(ORs) or risk ratios(RRs) with 95% confidence intervals(CIs) were pooled to assess the strength of association. Publication bias was estimated using funnel plots and the Egger’s regression test.

Results

A total of 17 studies with 2309 patients were included. The p16^INK4a overexpression was found to correlate significantly with the lower International Federation of Gynecology and Obstetrics stage(I+II vs III+IV; OR = 0.60,95%CI:0.41–0.86,P = 0.006),negative lymph node metastasis(negative vs positive; OR = 0.61,95%CI:0.39–0.95,P = 0.029),patient’s age<55(OR = 0.54,95%CI:0.31–0.96,P = 0.034),human papillomavirus–positive status(OR = 0.01,95%CI:0.00–0.11,P<0.001),and higher overall survival(RR = 0.53,95%CI = 0.35–0.80,P = 0.003).

Conclusion

The p16^INK4a might be associated with a higher survival and indicates better prognosis of vulvar cancer.     

Estimated Trans-Lamina Cribrosa Pressure Differences in Low-Teen and High-Teen Intraocular Pressure Normal Tension Glaucoma: The Korean National Health and Nutrition Examination Survey

Background

To investigate the association between estimated trans-lamina cribrosa pressure difference (TLCPD) and prevalence of normal tension glaucoma (NTG) with low-teen and high-teen intraocular pressure (IOP) using a population-based study design.

Methods

A total of 12,743 adults (≥ 40 years of age) who participated in the Korean National Health and Nutrition Examination Survey (KNHANES) from 2009 to 2012 were included. Using a previously developed formula, cerebrospinal fluid pressure (CSFP) in mmHg was estimated as 0.55 × body mass index (kg/m²) + 0.16 × diastolic blood pressure (mmHg)—0.18 × age (years)—1.91. TLCPD was calculated as IOP–CSFP. The NTG subjects were divided into two groups according to IOP level: low-teen NTG (IOP ≤ 15 mmHg) and high-teen NTG (15 mmHg < IOP ≤ 21 mmHg) groups. The association between TLCPD and the prevalence of NTG was assessed in the low- and high-teen IOP groups.

Results

In the normal population (n = 12,069), the weighted mean estimated CSFP was 11.69 ± 0.04 mmHg and the weighted mean TLCPD 2.31 ± 0.06 mmHg. Significantly higher TLCPD (p < 0.001; 6.48 ± 0.27 mmHg) was found in the high-teen NTG compared with the normal group. On the other hand, there was no significant difference in TLCPD between normal and low-teen NTG subjects (p = 0.395; 2.31 ± 0.06 vs. 2.11 ± 0.24 mmHg). Multivariate logistic regression analysis revealed that TLCPD was significantly associated with the prevalence of NTG in the high-teen IOP group (p = 0.006; OR: 1.09; 95% CI: 1.02, 1.15), but not the low-teen IOP group (p = 0.636). Instead, the presence of hypertension was significantly associated with the prevalence of NTG in the low-teen IOP group (p < 0.001; OR: 1.65; 95% CI: 1.26, 2.16).

Conclusions

TLCPD was significantly associated with the prevalence of NTG in high-teen IOP subjects, but not low-teen IOP subjects, in whom hypertension may be more closely associated. This study suggests that the underlying mechanisms may differ between low-teen and high-teen NTG patients.     

Riding the Kuroshio Current: Stepping stone dispersal of the Okinawa tree lizard across the East Asian Island Arc

Aim

Located hundreds of kilometres offshore of continental mainland Asia, the extremely high level of land vertebrate endemism in the East Asian Island Arc provides an excellent opportunity to test hypotheses regarding biogeographic processes and speciation. In this study, we aim to test alternative explanations for lineage diversification (vicariance versus dispersal models), and further develop a temporal framework for diversification in our focal taxon, which is consistent with the known age of these islands. We achieve these tests by investigating the historical biogeography of the Okinawa tree lizard (Japalura polygonata), one of the few widely‐distributed reptiles across this archipelago.

Location

The East Asian Island Arc: (1) Central Ryukyu (Amami and Okinawa groups); (2) Southern Ryukyu (Miyako and Yaeyama groups); (3) Taiwan and adjacent islands.

Methods

A total of 246 tissues were sampled from 10 localities in the Ryukyu archipelago and 17 localities in Taiwan, covering the entire distributional range of this species, including all subspecies. DNA sequences of the mitochondrial cytochrome b, 16S ribosomal RNA, nuclear BACH‐1 and RAG‐1 genes (total: 4,684 bp) were obtained from these samples. We used maximum likelihood and Bayesian methods to infer phylogeny and divergence time, and used a model‐fitting method of biogeographical inference to estimate ancestral range evolution.

Results

Multiple lines of evidence combine to identify a general pattern of dispersal‐mediated diversification northward through the archipelago, following initial dispersal from Taiwan. These included (1) a phylogenetic estimate, revealing a sequential, south‐to‐north branching pattern; (2) ancestral range estimation, inferring multiple overseas dispersals and subsequent colonization of new landmasses; and (3) a reduction in genetic variation observed in successively‐diverging lineages, decreasing from Taiwan northward, towards more remote islands. These results provide strong statistical support for an interpretation of successive bouts of dispersal via the powerful, well‐documented, south‐to‐north Kuroshio Current. Estimation of divergence times suggests that most clades in southern Ryukyu and Taiwan diverged early, giving rise to lineages that have remained isolated, and that more recently‐diverged lineages then colonized northward to subsequently occupy the landmasses of the Central Ryukyu archipelago.

Main conclusions

Our general inference of biogeographic history in Japalura polygonata suggested that this species originated on Taiwan and the Yaeyama group, and arrived at its current distribution in Miyako, Okinawa, Toku and Amami islands by a series of stepping‐stone dispersals, which we report for the first time for a terrestrial vertebrate endemic to this region.     

Complete Genome Sequence of a Mink Calicivirus in China

We report the complete genome sequence of a novel calicivirus isolated from a diseased mink in China. The complete viral genome is approximately 8.4 kb in length and consists of three open reading frames. The availability of the complete genome sequence is helpful for further investigation into the molecular characteristics and epidemiology of calicivirus in mink.     

Nippostrongylus brasiliensis: Effect of cyclophosphamide treatment on worm expulsion in rats

The precise immunological mechanisms associated with expulsion of the gastrointestinal nematode Nippostrongylus brasiliensis remain controversial. In order to investigate the effects of drug-induced immunosuppression on parasite burdens and expulsion, various regimens of cyclophosphamide were administered to parasitized Wistar rats. It was observed that both the number of worms established from an infective dose of 3000 larvae and the time of expulsion were markedly increased with higher doses of cyclophosphamide. Thus, at the highest sublethal level of treatment (100 mg/kg), 82% of the infective dose was recovered at Day 9 postinfection compared with 51% in nontreated controls. Furthermore, in such treated rats expulsion was delayed in 6 days beyond that of nontreated animals. As cyclophosphamide, at the levels used in the present study, is known to primarily effect B-cell function, the results support the view that antibody-mediated responses play an essential role in worm expulsion.     

高取代度CMS合成新工艺研究

研究以玉米淀粉为原料,用溶煤法合成CMS(2%水溶液,DS≥0.90,η≥120.0mpa.s)的新工艺;讨论了影响其合成的几种因素,确定了最佳技术参数和工艺条件,经工业性试验,证明本法切实可行。     

Microbial Products Induce Claudin-2 to Compromise Gut Epithelial Barrier Function

The epithelial barrier dysfunction is an important pathogenic feature in a number of diseases. The underlying mechanism is to be further investigated. The present study aims to investigate the role of tight junction protein claudin-2 (Cldn2) in the compromising epithelial barrier function. In this study, the expression of Cldn2 in the epithelial layer of mice and patients with food allergy was observed by immunohistochemistry. The induction of Cldn2 was carried out with a cell culture model. The Cldn2-facilitated antigen internalization was observed by confocal microscopy. The epithelial barrier function in the gut epithelial monolayer was assessed by recording the transepithelial resistance and assessing the permeability to a macromolecular tracer. The results showed that the positive immune staining of Cldn2 was observed in the epithelial layer of the small intestine that was weakly stained in naïve control mice, and strongly stained in sensitized mice as well as patients with food allergy. Exposure to cholera toxin or Staphylococcal enterotoxin B induced the expression of Cldn2 in HT-29 or T84 cells. Cldn2 could bind protein antigen to form complexes to facilitate the antigen transport across the epithelial barrier. Blocking Cldn2 prevented the allergen-related hypersensitivity the intestine. We conclude that the tight junction protein Cldn2 is involved in the epithelial barrier dysfunction.     

Dynamic recognition and repair of DNA complex damage

Irradiation (IR) can be used to treat cancer by inducing complex and irreparable DNA damage in the cancer cells, which may lead to their apoptotic death. However, little is known about the molecular mechanism of this DNA damage. Here, the non-small-cell lung cancer cell line A549 was treated with either X-ray or carbon ion combined with bleomycin (BLM). The cell survival rate, frequency of double-strand breaks (DSBs), dynamic changes in γH2AX, and p53 binding protein 1 (53BP1), and protein expression of Ku70, Rad51, and XRCC1 were determined by the clone formation assay, agarose gel electrophoresis, immunofluorescence, and western blot analysis. The results showed that the most obvious complex DSBs occurred in the carbon IR + BLM group. The number of γH2AX and 53BP1 foci in the 0.5 hr X-ray IR + BLM group was the highest (p < 0.001) among all the groups. γH2AX foci were detected in the nucleus at 0.5, 1, 2, and 4 hr, but were distributed throughout the cell at 6 hr after IR in the carbon ion IR + BLM group. The expression of Ku70 increased and XRCC1 decreased at 2 and 6 hr after IR. Our data indicate that a DNA damage frequency of 13.4/Mbp is caused by clustered DNA damage and further show a correlation between γH2AX, 53BP1, and XRCC1 levels and the extent of DNA damage. The results of this study provide insights into DNA damage recognition and a rationale for the clinical use of radiotherapy.