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871.
Guo-Qiang Zhang Jin-Liang Chen Ying Luo Maya B. Mathur Panagiotis Anagnostis Ulugbek Nurmatov Madar Talibov Jing Zhang Catherine M. Hawrylowicz Mary Ann Lumsden Hilary Critchley Aziz Sheikh Bo Lundbck Cecilia Lsser Hannu Kankaanranta Siew Hwa Lee Bright I. Nwaru 《PLoS medicine》2021,18(8)
BackgroundThere remains uncertainty about the impact of menopausal hormone therapy (MHT) on women’s health. A systematic, comprehensive assessment of the effects on multiple outcomes is lacking. We conducted an umbrella review to comprehensively summarize evidence on the benefits and harms of MHT across diverse health outcomes.Methods and findingsWe searched MEDLINE, EMBASE, and 10 other databases from inception to November 26, 2017, updated on December 17, 2020, to identify systematic reviews or meta-analyses of randomized controlled trials (RCTs) and observational studies investigating effects of MHT, including estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT), in perimenopausal or postmenopausal women in all countries and settings. All health outcomes in previous systematic reviews were included, including menopausal symptoms, surrogate endpoints, biomarkers, various morbidity outcomes, and mortality. Two investigators independently extracted data and assessed methodological quality of systematic reviews using the updated 16-item AMSTAR 2 instrument. Random-effects robust variance estimation was used to combine effect estimates, and 95% prediction intervals (PIs) were calculated whenever possible. We used the term MHT to encompass ET and EPT, and results are presented for MHT for each outcome, unless otherwise indicated. Sixty systematic reviews were included, involving 102 meta-analyses of RCTs and 38 of observational studies, with 102 unique outcomes. The overall quality of included systematic reviews was moderate to poor. In meta-analyses of RCTs, MHT was beneficial for vasomotor symptoms (frequency: 9 trials, 1,104 women, risk ratio [RR] 0.43, 95% CI 0.33 to 0.57, p < 0.001; severity: 7 trials, 503 women, RR 0.29, 95% CI 0.17 to 0.50, p = 0.002) and all fracture (30 trials, 43,188 women, RR 0.72, 95% CI 0.62 to 0.84, p = 0.002, 95% PI 0.58 to 0.87), as well as vaginal atrophy (intravaginal ET), sexual function, vertebral and nonvertebral fracture, diabetes mellitus, cardiovascular mortality (ET), and colorectal cancer (EPT), but harmful for stroke (17 trials, 37,272 women, RR 1.17, 95% CI 1.05 to 1.29, p = 0.027) and venous thromboembolism (23 trials, 42,292 women, RR 1.60, 95% CI 0.99 to 2.58, p = 0.052, 95% PI 1.03 to 2.99), as well as cardiovascular disease incidence and recurrence, cerebrovascular disease, nonfatal stroke, deep vein thrombosis, gallbladder disease requiring surgery, and lung cancer mortality (EPT). In meta-analyses of observational studies, MHT was associated with decreased risks of cataract, glioma, and esophageal, gastric, and colorectal cancer, but increased risks of pulmonary embolism, cholelithiasis, asthma, meningioma, and thyroid, breast, and ovarian cancer. ET and EPT had opposite effects for endometrial cancer, endometrial hyperplasia, and Alzheimer disease. The major limitations include the inability to address the varying effects of MHT by type, dose, formulation, duration of use, route of administration, and age of initiation and to take into account the quality of individual studies included in the systematic reviews. The study protocol is publicly available on PROSPERO (CRD42017083412).ConclusionsMHT has a complex balance of benefits and harms on multiple health outcomes. Some effects differ qualitatively between ET and EPT. The quality of available evidence is only moderate to poor.In an umbrella review, Guo-Qiang Zhang and colleagues comprehensively summarize evidence on the benefits and harms of menopausal hormone therapy across diverse health outcomes. 相似文献
872.
Denise M. Kenski Abby J. Cooper Jenny J. Li Aarron T. Willingham Henry J. Haringsma Tracy A. Young Nelly A. Kuklin Jeffrey J. Jones Mark T. Cancilla Daniel R. McMasters Melina Mathur Alan B. Sachs W. Michael Flanagan 《Nucleic acids research》2010,38(2):660-671
Small interfering RNAs (siRNAs) are short, double-stranded RNAs that use the endogenous RNAi pathway to mediate gene silencing. Phosphorylation facilitates loading of a siRNA into the Ago2 complex and subsequent cleavage of the target mRNA. In this study, 2′, 3′ seco nucleoside modifications, which contain an acylic ribose ring and are commonly called unlocked nucleic acids (UNAs), were evaluated at all positions along the guide strand of a siRNA targeting apolipoprotein B (ApoB). UNA modifications at positions 1, 2 and 3 were detrimental to siRNA activity. UNAs at positions 1 and 2 prevented phosphorylation by Clp1 kinase, abrogated binding to Ago2, and impaired Ago2-mediated cleavage of the mRNA target. The addition of a 5′-terminal phosphate to siRNA containing a position 1 UNA restored ApoB mRNA silencing, Ago2 binding, and Ago2 mediated cleavage activity. Position 1 UNA modified siRNA containing a 5′-terminal phosphate exhibited a partial restoration of siRNA silencing activity in vivo. These data reveal the complexity of interpreting the effects of chemical modification on siRNA activity, and exemplify the importance of using multiple biochemical, cell-based and in vivo assays to rationally design chemically modified siRNA destined for therapeutic use. 相似文献
873.
Aseefhali Bankapur Elsa Zachariah Santhosh Chidangil Manna Valiathan Deepak Mathur 《PloS one》2010,5(4)
An optical trap has been combined with a Raman spectrometer to make high-resolution measurements of Raman spectra of optically-immobilized, single, live red (RBC) and white blood cells (WBC) under physiological conditions. Tightly-focused, near infrared wavelength light (1064 nm) is utilized for trapping of single cells and 785 nm light is used for Raman excitation at low levels of incident power (few mW). Raman spectra of RBC recorded using this high-sensitivity, dual-wavelength apparatus has enabled identification of several additional lines; the hitherto-unreported lines originate purely from hemoglobin molecules. Raman spectra of single granulocytes and lymphocytes are interpreted on the basis of standard protein and nucleic acid vibrational spectroscopy data. The richness of the measured spectrum illustrates that Raman studies of live cells in suspension are more informative than conventional micro-Raman studies where the cells are chemically bound to a glass cover slip. 相似文献
874.
William P. Inskeep Douglas B. Rusch Zackary J. Jay Markus J. Herrgard Mark A. Kozubal Toby H. Richardson Richard E. Macur Natsuko Hamamura Ryan deM. Jennings Bruce W. Fouke Anna-Louise Reysenbach Frank Roberto Mark Young Ariel Schwartz Eric S. Boyd Jonathan H. Badger Eric J. Mathur Alice C. Ortmann Mary Bateson Gill Geesey Marvin Frazier 《PloS one》2010,5(3)
The Yellowstone caldera contains the most numerous and diverse geothermal systems on Earth, yielding an extensive array of unique high-temperature environments that host a variety of deeply-rooted and understudied Archaea, Bacteria and Eukarya. The combination of extreme temperature and chemical conditions encountered in geothermal environments often results in considerably less microbial diversity than other terrestrial habitats and offers a tremendous opportunity for studying the structure and function of indigenous microbial communities and for establishing linkages between putative metabolisms and element cycling. Metagenome sequence (14–15,000 Sanger reads per site) was obtained for five high-temperature (>65°C) chemotrophic microbial communities sampled from geothermal springs (or pools) in Yellowstone National Park (YNP) that exhibit a wide range in geochemistry including pH, dissolved sulfide, dissolved oxygen and ferrous iron. Metagenome data revealed significant differences in the predominant phyla associated with each of these geochemical environments. Novel members of the Sulfolobales are dominant in low pH environments, while other Crenarchaeota including distantly-related Thermoproteales and Desulfurococcales populations dominate in suboxic sulfidic sediments. Several novel archaeal groups are well represented in an acidic (pH 3) Fe-oxyhydroxide mat, where a higher O2 influx is accompanied with an increase in archaeal diversity. The presence or absence of genes and pathways important in S oxidation-reduction, H2-oxidation, and aerobic respiration (terminal oxidation) provide insight regarding the metabolic strategies of indigenous organisms present in geothermal systems. Multiple-pathway and protein-specific functional analysis of metagenome sequence data corroborated results from phylogenetic analyses and clearly demonstrate major differences in metabolic potential across sites. The distribution of functional genes involved in electron transport is consistent with the hypothesis that geochemical parameters (e.g., pH, sulfide, Fe, O2) control microbial community structure and function in YNP geothermal springs. 相似文献
875.
Root hairs provide a model system for studying tip growth in plants. The recent cloning of genes required for tip growth has shed new light on the link between ionic regulation, cell wall assembly and the cytoskeleton in cell growth. 相似文献
876.
Datta K Mathur SG Srivastava T Shah P Chattopadhyay P Sinha S 《The international journal of biochemistry & cell biology》2003,35(12):1639-1644
We had earlier shown that higher concentration of hydrogen peroxide (H2O2) induced p53-dependent apoptosis in glioma cell line with wild type p53 but had minimal effect on cells with mutated p53. Here we show a potentiating effect of hydroxylamine (HA), an inhibitor of catalase, on a nontoxic dose of H2O2 in glioma cells. HA sensitized both p53 wild type and mutated glioma cells to 0.25 mM H2O2. Potentiating effect of HA was independent of p53. Higher levels of reactive oxygen species (ROS) generation were observed in cells treated with HA+H2O2 as compared to cells treated with each component alone in both the cell lines. Dimethyl sulfoxide (DMSO) protected cells. Cytosolic cytochrome c and activated caspase 3 were detected at 4 h. The results suggest that higher levels of intracellular ROS, generated by HA+H2O2 act as a molecular switch in activating a rapidly acting p53-independent mitochondrial apoptotic pathway. 相似文献
877.
Selection and characterization of replicon variants dually resistant to thumb- and palm-binding nonnucleoside polymerase inhibitors of the hepatitis C virus 下载免费PDF全文
Le Pogam S Kang H Harris SF Leveque V Giannetti AM Ali S Jiang WR Rajyaguru S Tavares G Oshiro C Hendricks T Klumpp K Symons J Browner MF Cammack N Nájera I 《Journal of virology》2006,80(12):6146-6154
Multiple nonnucleoside inhibitor binding sites have been identified within the hepatitis C virus (HCV) polymerase, including in the palm and thumb domains. After a single treatment with a thumb site inhibitor (thiophene-2-carboxylic acid NNI-1), resistant HCV replicon variants emerged that contained mutations at residues Leu419, Met423, and Ile482 in the polymerase thumb domain. Binding studies using wild-type (WT) and mutant enzymes and structure-based modeling showed that the mechanism of resistance is through the reduced binding of the inhibitor to the mutant enzymes. Combined treatment with a thumb- and a palm-binding polymerase inhibitor had a dramatic impact on the number of replicon colonies able to replicate in the presence of both inhibitors. A more exact characterization through molecular cloning showed that 97.7% of replicons contained amino acid substitutions that conferred resistance to either of the inhibitors. Of those, 65% contained simultaneously multiple amino acid substitutions that conferred resistance to both inhibitors. Double-mutant replicons Met414Leu and Met423Thr were predominantly selected, which showed reduced replication capacity compared to the WT replicon. These findings demonstrate the selection of replicon variants dually resistant to two NS5B polymerase inhibitors binding to different sites of the enzyme. Additionally, these findings provide initial insights into the in vitro mutational threshold of the HCV NS5B polymerase and the potential impact of viral fitness on the selection of multiple-resistant mutants. 相似文献
878.
Majumder N Dey R Mathur RK Datta S Maitra M Ghosh S Saha B Majumdar S 《Glycoconjugate journal》2006,23(9):675-686
Various species of Mycobacteria produce a major cell wall-associated lipoglycan, called Lipoarabinomannan (LAM), which is involved in the virulence of Mycobacterial species. In this study, we tried to establish the role of the increased IL-10 secretion under Arabinosylated-LAM (Ara-LAM)
treatment, the LAM that induces apoptosis in host macrophages or PBMC. We have studied the survival and apoptotic factors
by western blotting, and estimated nitrite generation by Griess reaction, quantified iNOS mRNA by semi-quantitative RT-PCR,
and ultimately the fate of the cells were studied by Flow Cytometric Analysis of AnnexinV-FITC binding. As per our observations,
neutralization of released IL-10 in C57BL/6 peritoneal macrophages prior to Ara-LAM treatment, as well as macrophages from
IL-10 knockout (KO) mice treated with Ara-LAM, showed significant down regulation of pro-apoptotic factors and up regulation
of survival factors. These effects were strikingly similar to those when peritoneal macrophages were subjected to TNF-α and
IL-12 neutralization followed by Ara-LAM-treatment. However, under similar conditions virulent Mannosylated-LAM (from Mycobacterium tuberculosis) treatment of macrophages clearly depicts the importance of IL-10 in the maintenance of pathogenesis, proving its usual immunosuppressive
role. Thus, from our detailed investigations we point out an unusual pro-inflammatory action of IL-10 in Ara-LAM treated macrophages,
where it behaves in a similar manner as the known Th1 cytokines TNF- α and IL-12.
This work is financed by the Council of Scientific and Industrial Research (CSIR), Govt. of India. 相似文献
879.
Ankur Bhargava Sonal Saigal Pragya Thakur Uddipan Kumar Shreedevi Bhoi Shandar Siddiqui 《Bioinformation》2021,17(1):60
It is of interest to document data on morphometric (measurement of external form) analysis of maxillary and mandibular anterior teeth collected from a dental set up using mesio-distal (MD) dimension. The mesiodistal dimensions of all permanent anterior teeth (central incisor, lateral incisor and canine) of 25 males and 25 females patients were recorded using digital vernier calipers. Data were charted and statistical analysis was done using Mann Whitney U test. Data shows sexual dimorphism for every tooth between males and females. However, dimorphism was exhibited only in maxillary and mandibular canine, mandibular central incisors, and lateral incisor. Hence,odontometric parameters offer simple, reliable and cost-effective in forensic investigation for recording gender discrimination. 相似文献
880.
S K Rastogi B N Gupta T Husain N Mathur 《European journal of applied physiology and occupational physiology》1990,61(3-4):251-257
The cardiac cost of work and recovery pulse rates were evaluated in 38 glass bangle workers (mean age 27.8 years, SD 3.4) exposed to radiant heat (46.2 degrees C, SD 5.1) and high ambient temperature (38.2 degrees C, SD 3.4) for a mean period of 11.0 years, SD 3.5 in the glass bangle industry. A reference group of 15 controls (mean age 27.0 years, SD 3.5 unexposed to occupational heat stress served as a comparison. The results showed that the pulse rate increased from a mean basal value of 80.0 beats.min-1, SD 2.7 to 113.2 beats.min-1, SD 11.4 in the exposed workers while in the controls the increase was negligible. Thus the cardiac cost of work was found to be 33.2 beats.min-1, SD 11.1 in the exposed group which was significantly higher (P less than 0.001) than 7.8 beats.min-1, SD 4.2 observed in the control group. Among the exposed workers, 'belanias', who were engaged in the strenuous job of manually rotating the iron roller in the Belan furnace so that the molten glass could be wound in a spiral form, showed the maximum increase in the pulse rate (42.0 beats.min-1, SD 7.5) over the work-shift followed by 'muthias' (31.1 beats.min-1, SD 4.0) who were engaged in removing the glass spirals from the Belan furnace. However, wireman ('tarkashs'), who were engaged in the highly skilled job of making very fine threads of molten glass with the help of an iron roller, showed the smallest increase (19.5 beats.min-1, SD 3.4) in pulse rate over the work-shift.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献