MicroRNA Profiling and Head and Neck Cancer

Head and neck/oral cancer (HNOC) is a devastating disease. Despite advances in diagnosis and treatment, mortality rates have not improved significantly over the past three decades. Improvement in patient survival requires a better understanding of the disease progression so that HNOC can be detected early in the disease process and targeted therapeutic interventions can be deployed. Accumulating evidence suggests that microRNAs play important roles in many human cancers. They are pivotal regulators of diverse cellular processes including proliferation, differentiation, apoptosis, survival, motility, and morphogenesis. MicroRNA expression patterns may become powerful biomarkers for diagnosis and prognosis of HNOC. In addition, microRNA therapy could be a novel strategy for HNOC prevention and therapeutics. Recent advances in microRNA expression profiling have led to a better understanding of the cancer pathogenesis. In this review, we will survey recent technological advances in microRNA profiling and their applications in defining microRNA markers/targets for cancer prediction, diagnostics, treatment, and prognostics. MicroRNA alterations that consistently identified in HNOC will be discussed, such as upregulation of miR-21, miR-31, miR-155, and downregulation of miR-26b, miR-107, miR-133b, miR-138, and miR-139

High Viral Load of Human Bocavirus Correlates with Duration of Wheezing in Children with Severe Lower Respiratory Tract Infection

Background: Human bocavirus (HBoV) is a newly discovered parvovirus and increasing evidences are available to support its role as an etiologic agent in lower respiratory tract infection (LRTI). The objective of this study is to assess the impact of HBoV viral load on clinical characteristics in children who were HBoV positive and suffered severe LRTI. Methods: Lower respiratory tract aspirates from 186 hospitalized children with severe LRTI were obtained by bronchoscopy. HBoVs were detected by real-time PCR and other 10 infectious agents were examined using PCR and/or direct fluorescent assay. Results: Thirty-one patients (24.6%) were tested positive for HBoV in the respiratory tract aspirates. Fifteen samples had a high viral load (.10 4 copies/mL) and the other sixteen samples had a low viral load (,10 4 copies/mL). The duration of presented wheezing and hospitalization was longer in children with high viral load of HBoV than that in children with low viral load. The days of wheezing showed a correlation with viral load of HBoV. Conclusion: We confirmed that HBoV was frequently detected in patients with severe LRTI. Wheezing was one of the most common symptoms presented by patients with positive HBoV. A high HBoV viral load could be an etiologic agent for LRTI

Global Burden of Aortic Aneurysm and Attributable Risk Factors from 1990 to 2017

Background: To date, our understanding of the global aortic aneurysm (AA) burden distribution is very limited. Objective: To assess a full view of global AA burden distribution and attributable risk factors from 1990 to 2017. Methods: We extracted data of AA deaths, disability-adjusted life years (DALYs), and their corresponding age-standardized rates (ASRs), in general and by age/sex from the 2017 Global Burden of Disease (GBD) study. The current AA burden distribution in 2017 and its changing trend from 1990 to 2017 were separately showed. The spatial divergence was discussed from four levels: global, five social-demographic index regions, 21 GBD regions, and 195 countries and territories. We also estimated the risk factors attributable to AA related deaths. Results: Globally, the AA deaths were 167,249 with an age-standardized death rate (ASDR) of 2.19/100,000 persons in 2017, among which the elderly and the males accounted for the majority. Although reductions in ASRs were observed in developed areas, AA remained an important health issue in those relatively underdeveloped areas and might be much more important in the near future. AA may increasingly affect the elderly and the female population. Similar patterns of AA DALYs burden were noted during the study period. AA burden attributable to high blood pressure and smoking decreased globally and there were many heterogeneities in their distribution. Discussion: AA maintained an incremental public health issue worldwide. The change pattern of AA burden was heterogeneous across locations, ages, and sexes and it is paramount to improve resource allocation for more effective and targeted prevention strategies. Also, prevention of tobacco consumption and blood pressure control should be emphasized

Genistein suppresses FLT4 and inhibits human colorectal cancer metastasis

Dietary consumption of genistein, found in soy, has been associated with a potentially protective role in colorectal cancer (CRC) development and progression. Herein we demonstrate that genistein will inhibit human CRC cell invasion and migration, that it does so at non-cytotoxic concentrations and we demonstrate this in multiple human CRC cell lines. After orthotopic implantation of human CRC tumors into mice, oral genistein did not inhibit tumor growth, but did inhibit distant metastasis formation, and was non-toxic to mice. Using a qPCR array, we screened for genistein-induced changes in gene expression, followed by Western blot confirmation, demonstrating that genistein downregulated matrix metalloproteinase 2 and Fms-Related Tyrosine Kinase 4 (FLT4; vascular endothelial growth factor receptor 3). After demonstrating that genistein suppressed neo-angiogenesis in mouse tumors, we examined FLT4 expression in primary CRC and adjacent normal colonic tissue from 60 human subjects, demonstrating that increased FLT4 significantly correlates with increased stage and decreased survival. In summary, we demonstrate for the first time that genistein inhibits human CRC metastasis at dietary, non-toxic, doses. FLT4 is identified as a marker of metastatic disease, and as a response marker for small molecule therapeutics that inhibit CRC metastasis

GASZ promotes germ cell derivation from embryonic stem cells

AbstractPrimordial germ cells (PGCs) are the first germ-line population that forms from the proximal epiblast of the developing embryo. Despite their biological importance, the regulatory networks whereby PGCs arise, migrate, and differentiate into gametes during embryonic development remains elusive, largely due to the limited number of germ cells in the early embryo. To elucidate the molecular mechanisms that govern early germ cell development, we utilized an in vitro differentiation model of embryonic stem cells (ESCs) and screened a series of candidate genes with specific expression in the adult reproductive organs. We discovered that gain of function of Gasz, a gene previously reported to participate in meiosis of postnatal spermatocytes, led to the most robust upregulation of PGC formation from both human and murine ESCs. In contrast, Gasz deficiency resulted in pronounced reduction of germ cells during ESC differentiation and decreased expression of MVH and DAZL in genital ridges during early embryonic development. Further analyses demonstrated that GASZ interacted with DAZL, a key germ cell regulator, to synergistically promote germ cell derivation from ESCs. Thus, our data reveal a potential role of GASZ during embryonic germ cell development and provide a powerful in vitro system for dissecting the molecular pathways in early germ cell formation during embryogenesis

Uric acid predicts recovery of left ventricular function and adverse events in heart failure with reduced ejection fraction: Potential mechanistic insight from network analyses

Background and Aims: Heart failure with reduced ejection fraction (HFrEF) still carries a high risk for a sustained decrease in left ventricular ejection fraction (LVEF) even with the optimal medical therapy. Currently, there is no effective tool to stratify these patients according to their recovery potential. We tested the hypothesis that uric acid (UA) could predict recovery of LVEF and prognosis of HFrEF patients and attempted to explore mechanistic relationship between hyperuricemia and HFrEF. Methods: HFrEF patients with hyperuricemia were selected from the National Inpatient Sample (NIS) 2016-2018 database and our Xianyang prospective cohort study. Demographics, cardiac risk factors, and cardiovascular events were identified. Network-based analysis was utilized to examine the relationship between recovery of LVEF and hyperuricemia, and we further elucidated the underlying mechanisms for the impact of hyperuricemia on HFrEF. Results: After adjusting confounding factors by propensity score matching, hyperuricemia was a determinant of HFrEF [OR 1.247 (1.172-1.328); Conclusion: Lower baseline UA value predicted the LVEF recovery and less long-term adverse events in HFrEF patients. Our results provide new insights into underlying mechanistic relationship between hyperuricemia and HFrEF

Life history traits of low-toxicity alternative bisphenol S on Daphnia magna with short breeding cycles : A multigenerational study

Due to relatively lower toxicity, bisphenol S (BPS) has become an alternative to previously used bisphenol A. Nevertheless, the occurrence of BPS and its ecological impact have recently attracted increasing attentions because the toxicology effect of BPS with life cycle or multigenerational exposure on aquatic organisms remains questionable. Herein, Daphnia magna (D. magna) multigenerational bioassays spanning four generations (F0–F3) and single-generation recovery (F1 and F3) in clean water were used to investigate the ecotoxicology of variable chronic BPS exposure. For both assays, four kinds of life-history traits (i.e., survival, reproduction, growth and ecological behavior) were examined for each generation. After an 18-day exposure under concentration of 200 μg/L, the survival rate of D. magna was less than 15 % for the F2 generation, whereas all died for the F3 generation. With continuous exposure of four generations of D. magna at environmentally relevant concentrations of BPS (2 μg/L), inhibition of growth and development, prolonged sexual maturity, decreased offspring production and decreased swimming activity were observed for the F3 generation. In particular, it is difficult for D. magna to return to its normal level through a single-generation recovery in clean water in terms of reproductive function, ecological behavior and population health. Hence, multi-generational exposure to low concentrations of BPS can have adverse effects on population health of aquatic organisms with short breeding cycles, highlighting the necessity to assess the ecotoxicology of chronic BPS exposure for public health.publishedVersionPeer reviewe

Effect of transanal drainage tube on prevention of anastomotic leakage after anterior rectal cancer surgery taking indwelling time into consideration: a systematic review and meta-analysis

BackgroundPlacement of an indwelling transanal drainage tube (TDT) to prevent anastomotic leakage (AL) after anterior rectal cancer surgery has become a routine choice for surgeons in the recent years. However, the specific indwelling time of the TDT has not been explored. We performed this meta-analysis and considered the indwelling time a critical factor in re-analyzing the effectiveness of TDT placement in prevention of AL after anterior rectal cancer surgery.MethodsRandomized controlled trials (RCTs) and cohort studies which evaluated the effectiveness of TDT in prevention of AL after rectal cancer surgery and considered the indwelling time of TDT were identified using a predesigned search strategy in databases up to November 2022. This meta-analysis was performed to estimate the pooled AL rates (Overall and different AL grades) and reoperation rates at different TDT indwelling times and stoma statuses.ResultsThree RCTs and 15 cohort studies including 2381 cases with TDT and 2494 cases without TDT were considered eligible for inclusion. Our meta-analysis showed that the indwelling time of TDT for ≥5-days was associated with a significant reduction (TDT vs. Non-TDT) in overall AL (OR=0.46,95% CI 0.34-0.60, p<0.01), grade A+B AL (OR=0.64, 95% CI 0.42-0.97, p=0.03), grade C AL (OR=0.35, 95% CI 0.24-0.53, p<0.01), overall reoperation rate (OR=0.36, 95%CI 0.24-0.53, p<0.01) and that in patients without a prophylactic diverting stoma (DS) (OR=0.24, 95%CI 0.14-0.41, p<0.01). There were no statistically significant differences in any of the abovementioned indicators (p>0.05) when the indwelling time of TDT was less than 5 days.ConclusionExtending the postoperative indwelling time of TDT to 5 days may reduce the overall AL and the need for reoperation in patients without a prophylactic DS.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023407451, identifier CRD42023407451