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Homeobox transcript antisense intergenic RNA (HOTAIR), one of the well‐known long noncoding RNAs (lncRNAs), plays an important role in initiation and development of various tumors. Elevated level of HOTAIR is associated with metastatic behavior of primary tumor and poor outcome in several cancers. Therefore, we conducted a meta‐analysis to clearly measure the prognostic impact of HOTAIR in patients with digestive system carcinomas. Fourteen studies including 2,666 patients with five different type of digestive system cancers were selected to be entered in meta‐analysis. Finding demonstrated that HOTAIR overexpression could predict unfavorable outcome in digestive system carcinomas (hazard ratio [HR] = 2.4, 95% confidence interval [CI]: 2.0–2.9; p < 0.001; fixed‐effect model). In stratified analysis, increased level of HOTAIR predicted poor overall survival in gastric cancer (HR = 2.1, 95% CI: 1.6–2.9; p < 0.001), colorectal cancer (HR = 4.1, 95% CI: 1.6–10.2; p = 0.002), esophageal squamous cell carcinoma (HR = 2.3, 95% CI: 1.7–3.0; p < 0.001), and hepatocellular carcinoma (HR = 3.4, 95% CI: 1.9–6.1; p < 0.001). Our meta‐analysis results clearly support the prognostic value of HOTAIR to predict unfavorable prognostic outcomes in diverse digestive system carcinomas.

Advancing age leads to an accumulation of senescent endothelial cells (ECs) within arteries. Senescent cells have undergone permanent cell cycle arrest, are pro‐oxidative and pro‐inflammatory, and therefore represent a likely cause of age‐related EC dysfunction. Yet, the molecular mechanisms and physiological consequences of EC senescence remain incompletely understood. Telomeres are repeat DNA sequences that cap chromosomes. Telomeres shorten with each cell division and are highly susceptible to oxidative damage. When telomeres become critically short or damaged, they become uncapped, which activates the DNA damage response and leads to cellular senescence. Here, we tested the hypothesis that aging results in EC telomere uncapping that induces senescence, leading to physiological hallmarks of aging. To assess whether aging results in EC telomere uncapping, we compared ECs from young (~3 mo) and old (~27 mo) mice. Aging resulted in ~4‐fold greater EC telomere uncapping (p<0.001, Figure 1A). To determine if EC telomere uncapping induces senescence, we deleted the telomere capping protein, TRF2, in ECs of young (~3.5mo) mice (TRF2‐ecKO). Compared to wildtype (WT) littermate controls, TRF2‐ecKO mice had a ~78% reduction in TRF2 gene expression (p<0.0001). TRF2 deletion reduced EC division by ~47% (p<0.0001, Figure 1B), indicative of senescence. To examine the physiological consequences of EC senescence, we examined hallmarks of vascular aging including perfused microvascular density and endothelium‐dependent dilation (EDD). TRF2‐ecKO mice had an ~18% reduction in perfused mesenteric microvessels between 5‐25 µM (p<0.001, Figure 1C). Likewise, TRF2‐ecKO displayed ~26% reduction in mesenteric artery EDD compared to WT mice (p<0.05, Figure 1D). Furthermore, TRF2‐ecKO arterial EDD was ameliorated by the superoxide scavenger, TEMPOL (p>0.05, Figure 1D). Endothelium‐independent dilation to the exogenous nitric oxide donor sodium nitroprusside was not different between WT and TRF2‑ecKO mice (p>0.05). These data suggest EC telomere uncapping leads to senescence that reduces perfused microvascular density, and to elevated oxidative stress that suppresses EDD, similar to advanced age. To assess metabolic and muscle function, we performed an intraperitoneal glucose tolerance test (GTT, 2g/kg body mass) and a forelimb grip strength test. TRF2‐ecKO mice had ~21% greater area under the curve during GTT compared to WT mice (p<0.05, Figure 2A) as well as a ~14% reduction in grip strength (p<0.05, Figure2B). Taken together, these data provide evidence that aging results in EC telomere uncapping that induces senescence and age‐related physiological dysfunction.

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Background: Acquired Immunodeficiency Syndrome (AIDS) and tuberculosis (TB) represent major public health problems. The aim of this systematic review and meta-analysis is the assessment of the prevalence of tuberculosis, human immunodeficiency viruses (HIV), and co-infection of both, in pregnant women. Methods: We searched the literature in PubMed, Scopus, EMBASE, Web of Knowledge and MeSH, from all years of study until 25 April 2018, for articles and abstracts describing tuberculosis, HIV, and co-infection of HIV/TB during the pregnancy. Risk ratio (RRs) and 95% confidence interval (CI) for each outcome were combined, using a random-effects model. Eighteen studies met our inclusion criteria. Results: There was not an association between the incidence risk of tuberculosis during pregnancy in women without any underlying disease. (Risk ratio = 2.43, 95% CI = 0.97-6.08, p = 0.056, I 2 = 88.636, df (Q) = 4, Qvalue = 35.198). Pregnancy does not increase the incidence risk of HIV (Risk ratio = 1.27, 95% CI = 1-1.6, p = 0.00, I 2 = 81.024, df (Q) = 17, Q-value = 89.589). The prevalence of HIV has been investigated in three age groups of pregnant women [18-24 years (RR = 1.38), 25-34 years (RR = 1.12), and 35-44 years (RR = 1.71)], but there was not any significant association between the incidence of HIV and the age of the pregnancy. The risk ratio of tuberculosis in HIV positive pregnant women was 2.56 (summary: 95% CI = 1.57-4.17, p = 0.055, I 2 = 56.744, df (Q) = 4, Q-value = 9.247), and pregnancy in HIV positive women increased the incidence risk of tuberculosis. Conclusions: Pregnancy in HIV positive women was associated with an increased tuberculosis risk. Thus, prevention of tuberculosis incidents in these pregnant women would be critical for reducing vertical transmission from mother to child.

Aims. Bladder cancer (BCa) is a common cancer in North America and Europe that carries considerable morbidity and mortality. A reliable biomarker for early detection of the bladder is crucial for improving the prognosis of BCA. In this meta-analysis, we examine the diagnostic role of the angiogenin (ANG) protein in patients’ urine with bladder neoplasm. Methods. We performed a systematic literature search using ScienceDirect, Web of Science, PubMed/MEDLINE, Scopus, Google Scholar, and Embase, up to 10th October 2020 databases. Meta-Disc V.1.4 and Comprehensive Meta-Analysis V.2.2 software calculated the pooled specificity, sensitivity, area under the curve (AUC), diagnostic odds ratio (DOR), positive likelihood ratio (LR+), negative likelihood ratio (LR-), Q ∗ index, and summary receiver-operating characteristic (SROC) for the role of ANG as a urinary biomarker for BCa patients. Results. Four case-control studies were included with 656 participants (417 cases and 239 controls) in this meta-analysis. The pooled sensitivity of 0.71 (95% CI: 0.66–0.75), specificity of 0.78 (95% CI: 0.73–0.81), LR+ of 3.34 (95% CI: 2.02–5.53), LR- of 0.37 (95% CI: 0.32–0.44), DOR of 9.99 (95% CI: 4.69–21.28), and AUC of 0.789 and Q ∗ index of 0.726 demonstrate acceptable diagnostic precision of ANG in identifying BCa. Conclusion. This meta-analysis showed that ANG could be a fair biomarker for the diagnosis of BCa patients.

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The angiotensin-converting enzyme (ACE) is the major regulator of the reninangiotensin system, and it has been reported that genetic polymorphisms at this locus are associated with risk in numerous types of human cancers. In the current meta-analysis, we aimed to evaluate the association between the ACE Gene insertion/deletion (I/D) polymorphism (DD vs II) and digestive system cancer susceptibility. A total of 19 case-control studies among 3722 patients with seven different types of cancer were included in this meta-analysis. In the pooled analysis, the relationship between the ACE I/D polymorphism and digestive system cancer risk was not statistically significant (odds ratio [OR], 0.93; 95% confidence interval [CI], 0.68-1.29; P = 0.65; random model).Furthermore, subgroup analyses by cancer type also did not reveal an association between ACE polymorphisms and colorectal cancer (OR, 1.14; 95% CI, 0.823-1.58; P = 0.43; random effect model) and gastric cancer (OR, 0.79; 95% CI, 0.51-1.22; P = 0.28; random effect model). These findings indicate that ACE polymorphisms in the digestive tract may still affect the survival of cancer patients, and future studies into the topic of effect of ACE on cancer prognosis are warranted. K E Y W O R D Sangiotensin-converting enzyme, colorectal cancer, gastric cancer, Renin-angiotensin system | 19393