Identification Of Fetal Genomic Copy Number Deletions Associated With Preeclamptic Mothers In The Caucasian Population

Genetic determinants that are associated with preeclampsia still remain elusive nowadays, which might have resulted from limited understanding of the underlying pathogenesis mechanisms and the fetal contributions. By using genome-wide association study approach, we identified 2 candidate copy number deletions of the highest odds ratio ranking on chromosome 1 and 19, from 283 US white babies born by the mothers with preeclampsia. Based on the molecular and biological functions of the genes entailed the deleted regions, which contain CTSK, ARNT, and ACTN4, we proposed that these two candidate genomic deletions might be associated with preeclampsia. In a further attempt to replicate our findings in an independent dataset that contains 1200 white European babies, we did not find genes matched with our highest ranking candidates; however, one specific gene RYR1 deletion was identified in both datasets, and it can also be found in an established genetic database of preeclampsia genes. Our study was aimed to better understand the etiology of preeclampsia and in hopes to develop better screening tools based on genetic variants carried by the predisposed mother or fetus in the coming future

All-trans retinoic acid ameliorates glycemic control in diabetic mice via modulating pancreatic islet production of vascular endothelial growth factor-A.

Patients with type 1 diabetes mellitus are associated with impairment in vitamin A metabolism. This study evaluated whether treatment with retinoic acid, the biologically active metabolite of vitamin A, can ameliorate diabetes. All-trans retinoic acid (atRA) was used to treat streptozotocin (STZ)-induced diabetic mice which revealed atRA administration ameliorated blood glucose levels of diabetic mice. This hyperglycemic amelioration was accompanied by an increase in the amount of β cells co-expressed Pdx1 and insulin and by restoration of the vascular laminin expression. The atRA-induced production of vascular endothelial growth factor-A from the pancreatic islets was possibly the key factor that mediated the restoration of islet vascularity and recovery of β-cell mass. Furthermore, the combination of islet transplantation and atRA administration significantly rescued hyperglycemia in diabetic mice. These findings suggest that vitamin A derivatives can potentially be used as a supplementary treatment to improve diabetes management and glycemic control

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit

Race-, Age-, and Anatomic Site-Specific Gender Differences in Cutaneous Melanoma Suggest Differential Mechanisms of Early- and Late-Onset Melanoma.

In order to explore melanoma risk factors through gender-, age-, race-, and site-specific incidence rates, malignant melanoma cases from the Caucasian whites and non-whites were retrieved from the US SEER database. Age-standardized, age-, and site-specific tumor rates were calculated. All races and both genders showed positive annual average percentage changes (AAPCs) over the years, but AAPCs varied at different body sites, with men’s trunk exhibiting the fastest increase. Non-whites were diagnosed at a significantly younger age than whites and showed a trend towards fewer gender differences in the age of diagnosis. However, non-whites and whites showed a similar pattern of age-specific gender differences in the incidence rate ratios. A consistent spiked difference (female vs. male, incidence rate ratio (IRR) >2) was observed at or near the age of 20–24 in all race groups and at all body sites. The highest female vs. male IRR was found in the hip and lower extremities, and the lowest IRR was found in the head and neck region in all races. These race-, gender-, and site-dependent differences suggest that age-associated cumulative sun exposure weighs significantly more in late-onset melanomas, while genetics and/or pathophysiological factors make important contributions to early-onset melanomas

Reactive Oxygen Species-Associated Risk and Gender-Specific Risk Disparities of Cutaneous Melanoma

Cutaneous melanoma disproportionally affects the fair-skinned populations in the US and worldwide. UV radiation has long been recognized as the primary environmental cause of cutaneous melanoma. However, counterfactual evidence has indicated a non-straightforward relationship between UV radiation and melanoma transformation. For instance, melanoma tumors that grow on the body surface can be found in the non-UV-exposed regions such as the trunk, hip, and lower extremities. Melanoma incidence rates tend to be higher in adolescent and young adult females without a direct connection to excessive UV exposure. Nevertheless, few studies have investigated the impact of additional secondary drivers which contribute to the heterogeneity of melanoma tumors.The overarching goal of the current dissertation was to make a contribution to the research of secondary drivers in addition to UV radiation that play a role in the development of melanoma heterogeneity in diverse ethnic backgrounds. The specific aims include 1) determine the association between reactive oxygen species ‒ a leading secondary driver and risk factor for melanoma; 2) examine the age-dependent gender differences in the incidence rates of melanoma in multiple ethnic groups; 3) investigate the relationship between estrogen receptors’ signaling network and risk of melanoma.Utilizing the International Gene, Environment, and Melanoma Study dataset, a case-control design was performed to study the first aim. It turned out that the activator of NADPH oxidase complex 1 enzyme ‒ the RAC 1-GTPase, contributed to an oxidative stress-associated predisposed risk of melanoma in the fair-skinned population. The second aim was explored by using the US Surveillance, Epidemiology, and End Results Program (SEER) dataset. The results demonstrated a shared phenomenon of early disease onset in adolescent and young adult females in multiple ethnic groups regardless of skin color variations that have different sensitivities to the sun. In addition, the darker-skinned populations presented an even younger age of disease diagnosis than the fair-skinned population and the tumors that grow on the non-UV-exposed regions exhibited the fastest increase in incidence rates over the years. These findings suggested that female-sex is a pivotal secondary driver in addition to UV radiation in melanoma transformation. Therefore, the third aim carried out a genetic analysis of estrogen receptors’ signaling network in the fair-skinned population, in our preliminary attempts to explain the early melanoma-onset tendency introduced by female-sex. Using the NCBI High Density SNP Association Analysis of Melanoma: Case-Control and Outcomes Investigation dataset, findings showed that estrogen’s downstream IGF1 and its receptor IGF1R may play a critical role in the predisposed gender disparity of melanoma in the fair-skinned population. This current dissertation should lead to an improved melanoma UV-protection message that is currently conveyed to the public. Additionally, a female-sex-oriented message should be incorporated into educational campaigns to help improve melanoma primary prevention strategy

Reactive Oxygen Species-Associated Risk and Gender-Specific Risk Disparities of Cutaneous Melanoma

Cutaneous melanoma disproportionally affects the fair-skinned populations in the US and worldwide. UV radiation has long been recognized as the primary environmental cause of cutaneous melanoma. However, counterfactual evidence has indicated a non-straightforward relationship between UV radiation and melanoma transformation. For instance, melanoma tumors that grow on the body surface can be found in the non-UV-exposed regions such as the trunk, hip, and lower extremities. Melanoma incidence rates tend to be higher in adolescent and young adult females without a direct connection to excessive UV exposure. Nevertheless, few studies have investigated the impact of additional secondary drivers which contribute to the heterogeneity of melanoma tumors.The overarching goal of the current dissertation was to make a contribution to the research of secondary drivers in addition to UV radiation that play a role in the development of melanoma heterogeneity in diverse ethnic backgrounds. The specific aims include 1) determine the association between reactive oxygen species ‒ a leading secondary driver and risk factor for melanoma; 2) examine the age-dependent gender differences in the incidence rates of melanoma in multiple ethnic groups; 3) investigate the relationship between estrogen receptors’ signaling network and risk of melanoma.Utilizing the International Gene, Environment, and Melanoma Study dataset, a case-control design was performed to study the first aim. It turned out that the activator of NADPH oxidase complex 1 enzyme ‒ the RAC 1-GTPase, contributed to an oxidative stress-associated predisposed risk of melanoma in the fair-skinned population. The second aim was explored by using the US Surveillance, Epidemiology, and End Results Program (SEER) dataset. The results demonstrated a shared phenomenon of early disease onset in adolescent and young adult females in multiple ethnic groups regardless of skin color variations that have different sensitivities to the sun. In addition, the darker-skinned populations presented an even younger age of disease diagnosis than the fair-skinned population and the tumors that grow on the non-UV-exposed regions exhibited the fastest increase in incidence rates over the years. These findings suggested that female-sex is a pivotal secondary driver in addition to UV radiation in melanoma transformation. Therefore, the third aim carried out a genetic analysis of estrogen receptors’ signaling network in the fair-skinned population, in our preliminary attempts to explain the early melanoma-onset tendency introduced by female-sex. Using the NCBI High Density SNP Association Analysis of Melanoma: Case-Control and Outcomes Investigation dataset, findings showed that estrogen’s downstream IGF1 and its receptor IGF1R may play a critical role in the predisposed gender disparity of melanoma in the fair-skinned population. This current dissertation should lead to an improved melanoma UV-protection message that is currently conveyed to the public. Additionally, a female-sex-oriented message should be incorporated into educational campaigns to help improve melanoma primary prevention strategy

A cancer registry-based analysis on the non-white populations reveals a critical role of the female sex in early-onset melanoma.

PurposeMost melanoma studies have been performed in the white population who exhibits the highest incidence rate due to their skin sensitivity to UV radiation. Previous publications have shown that young women (approximately under the menopausal age) exhibit higher incidence rates than men of the same age, and the causes are mostly attributed to their sun behavior or indoor tanning. In our recent publications, we suggested that higher risk in younger women was due to pathophysiological factors, such as hormonal impact, and thus this higher risk in young women should be shared across ethnicities regardless of their skin color or UV behavior.MethodsA total of 13,208 non-white melanoma patients from SEER and 15,226 from WHO CI5-Plus were extracted for analysis. Age-specific incidence rates, female-to-male incidence rate ratios, and p values were calculated.ResultsAs observed in the white population, younger women and older men showed higher melanoma incidence rates than their peers of the other gender in all ethnic groups. The highest female-to-male incidence rate ratios were observed in the pubescent and reproductive ages. Previously this gender discrepancy in the white population was attributed to the preference of skin tanning in young females. There is no evidence to show that darker-skinned young females adopt a similar tanning preference. Thus the age-dependent gender difference in the risk of melanoma is shared across ethnic groups and is perhaps independent of UV behavior.ConclusionsOur results highlight the importance of gender as one of the melanoma risk factors beyond traditional UV radiation, which warrants further investigation and may provide a base for an improved prevention strategy