Recently, the evidence on efficacy and safety of prophylactic HPV vaccines derived from randomized trials was published in the Cochrane database of Systematic reviews. A summary of this Cochrane ...review is presented below.
Only trials involving mono-, bi-, and quadrivalent HPV vaccines were included. Trials evaluating the nonavalent vaccine were excluded since women in the control group received the quadrivalent vaccine. Main efficacy outcomes were: histologically confirmed cervical precancer lesions distinguishing those associated with vaccine HPV types and any cervical precancer. Exposure groups were: women aged: 15-26 or 24-45 years being initially negative for high-risk HPV (hrHPV) or negative for the vaccine types and women unselected by HPV status.
All evaluated vaccines offered excellent protection against cervical intraepithelial neoplasia of grade 2 or 3 (CIN2 or CIN3) and adenocarcinoma in situ associated with HPV16/18 infection in young women who were not initially infected with hrHPV or HPV16/18. Vaccine efficacy was lower when all women regardless of HPV DNA status at enrollment were included. In young women, HPV vaccination protected also against any cervical precancer but the magnitude of protection was lower than against HPV16/18 associated cervical precancer. Vaccine efficacy was lower in mid-adult (aged 24-45 years) women. No protection against cervical precancer was found in mid-adult women unselected by HPV DNA status at enrollment. Trials were not empowered to address protection against cervical cancer. Occurrence of severe adverse events or adverse pregnancy outcomes was not significantly higher in recipients of HPV vaccines than in women included in the control arms.
Dioscin, one natural product, has various pharmacological actions. However, its effects on methotrexate (MTX)-induced hepatorenal damages still remain unknown. In the present study, the data ...manifested that dioscin restored the viabilities of L-02 and NRK-52E cells, reduced ALT, AST, Cr, BUN levels, and ameliorated histopathological changes of liver and kidney. Besides, dioscin decreased ROS levels in cells, and adjusted SOD, MDA, GSH and GSH-Px levels in rats. Dioscin reduced the expression levels of miR-145–5p which directly targeted Sirt5, and then regulated the expression levels of SOD1, Nrf2, Gst, Keap1, HO-1, GCLC and NQO1. MiR-145–5p mimic in cells deteriorated ROS levels and decreased Sirt5 expression to accentuate oxidative stress by regulating the expression levels of SOD1, Nrf2, Keap1, which were all reversed by dioscin. Moreover, MTX-induced hepatorenal damage were worsened in mice by Sirt5 siRNA or miR-145–5p agomir, which were also alleviated by dioscin. Dioscin relieved MTX-induced hepatorenal damages through regulating miR-145-5p-medicated oxidative stress, which should be considered as one effective drug to treat the disorder in future.
Proposed signaling mechanism of dioscin on restoring MTX-induced liver and kidney damages via regulating miR-145-5p-mediated oxidative stress. Dioscin up-regulated Sirt5 level by down-regulating miR-145–5p level to adjust the expression levels of Nrf2, HO-1, GCLC, NQO1, Gst, SOD1 and Keap1. Dioscin protected hepatorenal damages caused by MTX via regulating miR-145-5p-mediated oxidative stress. Display omitted
•Dioscin significantly relieved MTX-induced hepatorenal damages in vitro and in vivo.•MTX caused oxidative damages to the liver and kidney in vitro and in vivo.•miR-145–5p directly targeted Sirt5 to adjust oxidative stress.•Dioscin reduced the expression levels of miR-145–5p and suppressed w miR-145-5p-medicated oxidative stress.
Icariin was evaluated for its antiosteoporotic activity in an ovariectomized rat model of osteoporosis. The rats were divided into sham and OVX groups. The OVX rats were then subdivided into five ...groups treated with water, nylestriol (1
mg/kg body weight, weekly, orally) or icariin (ICA) (5, 25, and 125
mg/kg body weight, daily, orally) for 12 weeks. In OVX rats, the increases of body weight, serum BGP and ALP were significantly decreased by ICA treatment. In OVX rats, atrophy of uterus and descent of BMD were suppressed by treatment with ICA. In addition, ICA (125
mg/kg body weight) completely corrected the decreased serum concentration of Calcium, Phosphorus, and E
2 observed in OVX rats. ICA (125
mg/kg body weight) increased biomechanical strength significantly in comparison to the sham group. Histological results also showed its protective action through promotion of bone formation. The findings, assessed on the basis of biochemical, bone mineral density, biomechanical, and histopathological parameters, showed that ICA has a definite antiosteoporotic effect, similar to estrogen, especially effective for prevention bone fracture induced by estrogen deficiency.
Summary
Clonostachys rosea is a promising saprophytic filamentous fungus that belongs to phylum Ascomycota. Clonostachys rosea is widespread around the world and exists in many kinds of habitats, ...with the highest frequency in soil. As an excellent mycoparasite, C. rosea exhibits strong biological control ability against numerous fungal plant pathogens, nematodes and insects. These behaviours are based on the activation of multiple mechanisms such as secreted cell‐wall‐degrading enzymes, production of antifungal secondary metabolites and induction of plant defence systems. Besides having significant biocontrol activity, C. rosea also functions in the biodegradation of plastic waste, biotransformation of bioactive compounds, as a bioenergy sources and in fermentation. This mini review summarizes information about the biology and various applications of C. rosea and expands on its possible uses.
Encouraging results from a small sample of patients with myelodysplastic syndrome (MDS) undergoing haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) must be extended. ...Furthermore, an algorithm derived from a comparison of the outcomes of HID and identical-sibling donor (ISD) HSCT must be established. Therefore, the outcomes of 454 MDS patients who underwent HSCT from HIDs (n=226) or ISDs (n=228) between 2003 and 2013 that were reported to the Chinese Bone Marrow Transplantation Registry were analyzed. Among the 3/6 HID (n=136), 4-5/6 HID (n=90) and ISD patient groups, the 4-year adjusted cumulative incidences of non-relapse mortality were 34, 29 and 16%, respectively (overall P=0.004), and of relapse were 6, 7 and 10%, respectively (overall P=0.36). The 4-year adjusted probabilities of overall survival were 58, 63 and 73%, respectively (overall P=0.07), and of relapse-free-survival were 58, 63 and 71%, respectively (overall P=0.14); pairwise comparison showed that the difference was only statistically significant in the 3/6 HID vs ISD pair. The data suggest that ISDs remain the best donor source for MDS patients while HIDs (perhaps 4-5/6 HID in particular) could be a valid alternative when an ISD is not available; human leukocyte antigen disparity had no effect on survival among the HID patients.
Glycolysis is critical for cancer stem cell reprogramming; however, the underlying regulatory mechanisms remain elusive. Here, we show that pyruvate dehydrogenase kinase 1 (PDK1) is enriched in ...breast cancer stem cells (BCSCs), whereas depletion of PDK1 remarkably diminishes ALDH
subpopulations, decreases stemness-related transcriptional factor expression, and inhibits sphere-formation ability and tumor growth. Conversely, high levels of PDK1 enhance BCSC properties and are correlated with poor overall survival. In mouse xenograft tumor, PDK1 is accumulated in hypoxic regions and activates glycolysis to promote stem-like traits. Moreover, through screening hypoxia-related long non-coding RNAs (lncRNAs) in PDK1-positive tissue, we find that lncRNA H19 is responsible for glycolysis and BCSC maintenance. Furthermore, H19 knockdown decreases PDK1 expression in hypoxia, and ablation of PDK1 counteracts H19-mediated glycolysis and self-renewal ability in vitro and in vivo. Accordingly, H19 and PDK1 expression exhibits strong correlations in primary breast carcinomas. H19 acting as a competitive endogenous RNA sequesters miRNA let-7 to release Hypoxia-inducible factor 1α, leading to an increase in PDK1 expression. Lastly, aspirin markedly attenuates glycolysis and cancer stem-like characteristics by suppressing both H19 and PDK1. Thus, these novel findings demonstrate that the glycolysis gatekeeper PDK1 has a critical role in BCSC reprogramming and provides a potential therapeutic strategy for breast malignancy.
Brown carbon aerosol consists of light‐absorbing organic particulate matter with wavelength‐dependent absorption. Aerosol optical extinction, absorption, size distributions, and chemical composition ...were measured in rural Alabama during summer 2013. The field site was well located to examine sources of brown carbon aerosol, with influence by high biogenic organic aerosol concentrations, pollution from two nearby cities, and biomass burning aerosol. We report the optical closure between measured dry aerosol extinction at 365 nm and calculated extinction from composition and size distribution, showing agreement within experiment uncertainties. We find that aerosol optical extinction is dominated by scattering, with single‐scattering albedo values of 0.94 ± 0.02. Black carbon aerosol accounts for 91 ± 9% of the total carbonaceous aerosol absorption at 365 nm, while organic aerosol accounts for 9 ± 9%. The majority of brown carbon aerosol mass is associated with biomass burning, with smaller contributions from biogenically derived secondary organic aerosol.
Key Points
Aerosol optical extinction in the southeastern U.S. is dominated by scattering
Black carbon is a more significant absorber than organic carbon at 365 nm
Biomass burning makes the largest contribution to organic aerosol absorption
Recent evidence highlights long noncoding RNAs (lncRNAs) as crucial regulators of cancer biology that contribute to tumorigenesis. LncRNA TUG1 was initially detected in a genomic screen for genes ...upregulated in response to taurine treatment in developing mouse retinal cells. Our previous study showed that TUG1 could affect cell proliferation through epigenetically regulating HOXB7 in human non-small cell lung cancer. However, the clinical significance and potential role of TUG1 in GC remains unclear. In this study, we found that TUG1 is significantly increased and is correlated with outcomes in gastric cancer (GC). Further experiments revealed that knockdown of TUG1 repressed GC proliferation both in vitro and in vivo. Mechanistic investigations showed that TUG1 has a key role in G0/G1 arrest. We further demonstrated that TUG1 was associated with PRC2 and that this association was required for epigenetic repression of cyclin-dependent protein kinase inhibitors, including p15, p16, p21, p27 and p57, thus contributing to the regulation of GC cell cycle and proliferation. Together, our results suggest that TUG1, as a regulator of proliferation, may serve as a candidate prognostic biomarker and target for new therapies in human GC.
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