Regulation of angiogenic factors by pituitary tumor transforming gene (PTTG) in tumorigenesis.

Pituitary tumor transforming gene ( PTTG ), also known as securing, is a novel oncogene that is expressed at high levels in most of the tumors analyzed to date. Overexpression of PTTG in mouse fibroblast(NIH 3T3) cells increases cell proliferation, induces cellular transformation and promotes tumor formation in nude mice. PTTG is a multi-domain and multifunction protein. Some functions of PTTG include inhibition of pre-mature sister chromatid separation, activation of transcription of c-myc oncogene, cell cycle regulation, and DNA repair. In some cancers such as thyroid, pituitary, esophageal, and colorectal tumors, high PTTG expression correlates with metastasis and poor prognosis. The PTTG gene encodes a protein of 203 amino acids and is consists of six exons and four introns. The PTTG promoter is specifically activated in tumors and is highly regulated by Spl and NF-Y nuclear factors. However, the precise mechanism by which PTTG mediates its tumorigenic function remains unclear. To this end, we determined the effect of PTTG on tumor metastasis and angiogenesis by determining its effect on secretion and expression of various angiogenic and metastatic factors including bFGF, VEGF, IL-8 and MMP-2. Using RT/PCR, ELISA and zymography we showed a significant increase in expression and secretion of bFGF, VEGF, IL-8 and MMP-2 in HEK293 cells on transfection of PTTG cDNA. Down regulation of PTTG expression by siRNA and a genetically deleted HCTI 1\u276 (PTTG -/-) cell line showed significantly decrease in expression of MMP-2, which led to decreased invasion and migration of HCT116 (PTTG-/-) cells as compared to the HCT116 wild type. Taken together, our results confirm that PTTG is a potent tumorigenic gene that exerts its tumorigenic functions by increasing secretion and expression of VEGF, bFGF, IL-8 and MMP-2 and MTl-MMP. In addition expression of other angiogenic and adhesion molecules including beta-1, beta-3, alpha-5 and alpha-V integrins was also modulated by PTTG in HEK293 cells

On the Structural Analysis of γ

Oriented allyl radicals are detected at room temperature in gamma irradiated UHMWPE. The effects of vitamin E and storage at room temperature on this oriented structure are also investigated during the study. While testing powder as well as compression-molded solids, with or without vitamin E, a typical ESR spectrum was recorded at room temperature following 100 kGy gamma dose and subsequent storage at −78.5°C for one year. The simulated results show that the relative abundance of 5% alkyl, 68% allyl, and 27% polyenyl produced a 98.7% best fit of experimental ones. Furthermore, the allyl radical signal gives approximately 20% of random orientations and 80% of oriented molecules. In oriented PE, measured at −196°C, Ohnishi et al. (1916) observed 25 lines within a total magnetic field width of approximately 133 G. Our spectra also show 25 lines spread over 136 G in UHMWPE powder samples and at room temperature after one year of storage

N-[4-(Phenyl­imino­meth­yl)phen­yl]acetamide 0.67-hydrate

The title compound, C15H14N2O·0.67H2O, was prepared by the reaction of 4-acetoamine­benzaldehyde and aniline. The asymmetric unit contains six organic mol­ecules and four water mol­ecules. The dihedral angles between the aromatic ring planes in each organic mol­ecule vary from 42.4 (2) to 53.8 (2)°. In the crystal, an extensive network of inter­molecular N—H⋯O, O—H⋯N and O—H⋯O hydrogen bonds link the mol­ecules into [010] chains

Gold Nanoplates as Cancer-Targeted Photothermal Actuators for Drug Delivery and Triggered Release

The selective exposure of cancerous tissue to systemically delivered chemotherapeutic agents remains a major challenge facing cancer therapy. To address this question, a near infrared responsive oligonucleotide-coated (AS1411, hairpin, or both) gold nanoplate loaded with doxorubicin is demonstrated to be nontoxic to cells without triggered release, while being acutely toxic to cells after 5 minutes of laser exposure to trigger DOX release. Conjugation of oligonucleotides to the nanoplates is confirmed by an average increase in hydrodynamic diameter of 30.6 nm, an average blue shift of the plasmon resonance peak by 36 nm, and an average −10 mV shift in zeta potential of the particles. DOX loading through intercalation into the hairpin DNA structure is confirmed through fluorescence measurements. For both GNP-Hairpin and GNP-Hairpin-AS1411, ~60% of loaded DOX is released after the first 5 minutes of laser exposure (λ=817 nm), with complete release after two more 5-minute exposures. Preliminary proof of concept is demonstrated in vitro using A549 and MDA-MB-231 cell lines as models for breast and lung cancer, respectively. Exposure of cells to untriggered DOX-loaded conjugate with no laser exposure results in little to no toxicity, while laser-triggered release of DOX causes significant cell death

A Review on Key Issues and Challenges in Devices Level MEMS Testing

The present review provides information relevant to issues and challenges in MEMS testing techniques that are implemented to analyze the microelectromechanical systems (MEMS) behavior for specific application and operating conditions. MEMS devices are more complex and extremely diverse due to the immersion of multidomains. Their failure modes are distinctive under different circumstances. Therefore, testing of these systems at device level as well as at mass production level, that is, parallel testing, is becoming very challenging as compared to the IC test, because MEMS respond to electrical, physical, chemical, and optical stimuli. Currently, test systems developed for MEMS devices have to be customized due to their nondeterministic behavior and complexity. The accurate measurement of test systems for MEMS is difficult to quantify in the production phase. The complexity of the device to be tested required maturity in the test technique which increases the cost of test development; this practice is directly imposed on the device cost. This factor causes a delay in time-to-market

Phytochemical Profile, Biological Properties, and Food Applications of the Medicinal Plant Syzygium cumini

Syzygium cumini, locally known as Jamun in Asia, is a fruit-bearing crop belonging to the Myrtaceae family. This study aims to summarize the most recent literature related to botany, traditional applications, phytochemical ingredients, pharmacological activities, nutrition, and potential food applications of S. cumini. Traditionally, S. cumini has been utilized to combat diabetes and dysentery, and it is given to females with a history of abortions. Anatomical parts of S. cumini exhibit therapeutic potentials including antioxidant, anti-inflammatory, analgesic, antipyretic, antimalarial, anticancer, and antidiabetic activities attributed to the presence of various primary and secondary metabolites such as carbohydrates, proteins, amino acids, alkaloids, flavonoids (i.e., quercetin, myricetin, kaempferol), phenolic acids (gallic acid, caffeic acid, ellagic acid) and anthocyanins (delphinidin-3,5-O-diglucoside, petunidin-3,5-O-diglucoside, malvidin-3,5-O-diglucoside). Different fruit parts of S. cumini have been employed to enhance the nutritional and overall quality of jams, jellies, wines, and fermented products. Today, S. cumini is also used in edible films. So, we believe that S. cumini’s anatomical parts, extracts, and isolated compounds can be used in the food industry with applications in food packaging and as food additives. Future research should focus on the isolation and purification of compounds from S. cumini to treat various disorders. More importantly, clinical trials are required to develop low-cost medications with a low therapeutic inde

A Review on Key Issues and Challenges in Devices Level MEMS Testing

The present review provides information relevant to issues and challenges in MEMS testing techniques that are implemented to analyze the microelectromechanical systems (MEMS) behavior for specific application and operating conditions. MEMS devices are more complex and extremely diverse due to the immersion of multidomains. Their failure modes are distinctive under different circumstances. Therefore, testing of these systems at device level as well as at mass production level, that is, parallel testing, is becoming very challenging as compared to the IC test, because MEMS respond to electrical, physical, chemical, and optical stimuli. Currently, test systems developed for MEMS devices have to be customized due to their nondeterministic behavior and complexity. The accurate measurement of test systems for MEMS is difficult to quantify in the production phase. The complexity of the device to be tested required maturity in the test technique which increases the cost of test development; this practice is directly imposed on the device cost. This factor causes a delay in time-to-market

National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma

©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.Peer reviewe

COVID-19 vaccine acceptance and hesitancy in low- and middle-income countries

Widespread acceptance of COVID-19 vaccines is crucial for achieving sufficient immunization coverage to end the global pandemic, yet few studies have investigated COVID-19 vaccination attitudes in lower-income countries, where large-scale vaccination is just beginning. We analyze COVID-19 vaccine acceptance across 15 survey samples covering 10 low- and middle-income countries (LMICs) in Asia, Africa and South America, Russia (an upper-middle-income country) and the United States, including a total of 44,260 individuals. We find considerably higher willingness to take a COVID-19 vaccine in our LMIC samples (mean 80.3%; median 78%; range 30.1 percentage points) compared with the United States (mean 64.6%) and Russia (mean 30.4%). Vaccine acceptance in LMICs is primarily explained by an interest in personal protection against COVID-19, while concern about side effects is the most common reason for hesitancy. Health workers are the most trusted sources of guidance about COVID-19 vaccines. Evidence from this sample of LMICs suggests that prioritizing vaccine distribution to the Global South should yield high returns in advancing global immunization coverage. Vaccination campaigns should focus on translating the high levels of stated acceptance into actual uptake. Messages highlighting vaccine efficacy and safety, delivered by healthcare workers, could be effective for addressing any remaining hesitancy in the analyzed LMICs.Publisher PDFPeer reviewe

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions