scholarly journals The influence of age and sex on the pre-treatment immune microenvironment of a carcinogen induced murine model of bladder cancer

2021 ◽  
Author(s):  
Ali Hamade ◽  
Deyang Li ◽  
Kathrin Tyryshkin ◽  
Minqi Xu ◽  
Stephen Chenard ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Clinical Outcomes ◽  
Age Groups ◽  
Immune Microenvironment ◽  
High Endothelial Venules ◽  
Similar Frequency ◽  
Male And Female ◽  
Female Mice ◽  
Age Related ◽  
Immune Profiling

AbstractThe incidence of urothelial carcinoma of the bladder is four times higher in males than females; however, females tend to present with a more aggressive disease, a poorer response to immunotherapy and suffer worse clinical outcomes. Recent findings have demonstrated sexual dimorphism in the tumor immune microenvironment of non-muscle invasive bladder cancer and associated clinical outcomes. However, a significant gap in knowledge remains with respect to the current pre-clinical modeling approaches and more precisely recapitulating these differences towards improved therapeutic design. Based on the similarities in mucosal immune physiology between humans and mice, we evaluated the sex and age-related immune alterations in healthy murine bladders. Bulk-RNA sequencing and multiplex immunofluorescence based spatial immune profiling of healthy murine bladders from male and female mice of age groups spanning young to old showed a highly altered immune landscape that exhibited sex and age associated differences, particularly in the context of B cell associated responses. Spatial profiling using markers specific to macrophages, T lymphocytes, B lymphocytes, activated dendritic cells, high endothelial venules, myeloid cells and the PD-L1 immune checkpoint showed sex and age associated differences. Bladders from healthy older female mice showed a higher number of tertiary lymphoid structures (TLSs) compared to both young female and male equivalents. Spatial immune profiling of N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) carcinogen exposed male and female bladders from young and old mice revealed a similar frequency of TLS formation, sex differences in the bladder immune microenvironment and, age differences in latency of tumor induction. These findings support the incorporation of sex and age as factors in pre-clinical modeling of NMIBC and will potentially advance the field of immunotherapeutic drug development to improve clinical outcomes in NMIBC.

scholarly journals NPY Deficiency Prevents Postmenopausal Adiposity by Augmenting Estradiol-Mediated Browning

2018 ◽  
Vol 75 (6) ◽  
pp. 1042-1049
Author(s):  
Seongjoon Park ◽  
Erkhembayar Nayantai ◽  
Toshimitsu Komatsu ◽  
Hiroko Hayashi ◽  
Ryoichi Mori ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Fat Metabolism ◽  
Male Mice ◽  
Wild Type ◽  
Male And Female ◽  
Female Mice ◽  
Age Related ◽  
Promising Target ◽  
Intracellular Mechanism

Abstract The orexigenic hormone neuropeptide Y (NPY) plays a pivotal role in the peripheral regulation of fat metabolism. However, the mechanisms underlying the effects of sex on NPY function have not been extensively analyzed. In this study, we examined the effects of NPY deficiency on fat metabolism in male and female mice. Body weight was slightly decreased, whereas white adipose tissue (WAT) mass was significantly decreased as the thermogenic program was upregulated in NPY-/- female mice compared with that in wild-type mice; these factors were not altered in response to NPY deficiency in male mice. Moreover, lack of NPY resulted in an increase in luteinizing hormone (LH) expression in the pituitary gland, with concomitant activation of the estradiol-mediated thermogenic program in inguinal WAT, and alleviated age-related modification of adiposity in female mice. Taken together, these data revealed a novel intracellular mechanism of NPY in the regulation of fat metabolism and highlighted the sexual dimorphism of NPY as a promising target for drug development to reduce postmenopausal adiposity.

Sex Differences in the Relation Between Frailty and Endothelial Dysfunction in Old Mice

2021 ◽  
Author(s):  
Jazmin A Cole ◽  
Mackenzie N Kehmeier ◽  
Bradley R Bedell ◽  
Sahana Krishna Kumaran ◽  
Grant D Henson ◽  
...  
Keyword(s):  
Sex Differences ◽  
Endothelial Function ◽  
Vascular Function ◽  
Mesenteric Artery ◽  
Frailty Index ◽  
Mesenteric Arteries ◽  
Male Mice ◽  
Male And Female ◽  
Female Mice ◽  
Age Related

Abstract Vascular endothelial function declines with age on average, but there is high variability in the magnitude of this decline within populations. Measurements of frailty, known as frailty index (FI), can be used as surrogates for biological age, but it is unknown if frailty relates to the age-related decline in vascular function. To examine this relation, we studied young (4-9 months) and old (23-32 months) C57BL6 mice of both sexes. We found that FI was greater in old compared with young mice, but did not differ between old male and female mice. Middle cerebral artery (MCA) and mesenteric artery endothelium-dependent dilation (EDD) also did not differ between old male and female mice; however, there were sex differences in the relations between FI and EDD. For the MCA, FI was inversely related to EDD among old female mice, but not old male mice. In contrast, for the mesenteric artery, FI was inversely related to EDD among old male mice, but not old female mice. A higher FI was related to a greater improvement in EDD with the superoxide scavenger TEMPOL in the MCAs for old female mice and in the mesenteric arteries for old male mice. FI related to mesenteric artery gene expression negatively for extracellular superoxide dismutase (Sod3) and positively for interleukin-1β (Il1b). In summary, we found that the relation between frailty and endothelial function is dependent on sex and the artery examined. Arterial oxidative stress and pro-inflammatory signaling are potential mediators of the relations of frailty and endothelial function.

Parental PM2.5 Exposure-Promoted Development of Metabolic Syndrome in Offspring Is Associated With the Changes of Immune Microenvironment

2019 ◽  
Vol 170 (2) ◽  
pp. 415-426 ◽  
Author(s):  
Jia Zhang ◽  
Xuejiao Zeng ◽  
Xihao Du ◽  
Kun Pan ◽  
Liying Song ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Fine Particulate Matter ◽  
Density Lipoprotein ◽  
Model Assessment ◽  
Immune Microenvironment ◽  
Male And Female ◽  
Female Mice ◽  
Parental Exposure ◽  
Pm2.5 Exposure

Abstract Parental exposure to ambient fine particulate matter (PM2.5) has been associated with some of adverse health outcomes in offspring. The association between parental PM2.5 exposure and the development of metabolic syndrome (MetS) in offspring, and the effects of parental PM2.5 exposure on the susceptibility of offspring mice to PM2.5, has not been evaluated. The C57BL/6 parental mice (male and female mice) were exposed to filtered air (FA) or concentrated PM2.5 (PM) using Shanghai-METAS for a total of 16 weeks. At week 12 during the exposure, we allowed the parental male and female mice to breed offspring mice. The male offspring mice were divided into 4 groups and exposed to PM and FA again. The results showed that whether the parental mice were exposed to PM2.5 or not, the offspring mice exposure to PM2.5 appeared the elevation of blood pressure, insulin resistance, impairment of glucose tolerance, and dyslipidemia when compared to the offspring mice exposure to FA. More importantly, no matter what the offspring mice were exposed to, parental PM exposure overwhelmingly impacted the fasting blood insulin, homeostasis model assessment-insulin resistance, serous low-density lipoprotein cholesterol, and total cholesterol, splenic T helper cell 17 (Th17) and Treg cells, serous interleukin (IL)-17A, IL-6, and IL-10 in offspring mice. The results suggested that the parental exposure to air pollution might induce the development of MetS in offspring and might enhance the susceptibility of offspring to environmental hazards. The effects of parental PM exposure on offspring might be related to the changes of immune microenvironment.

scholarly journals The effect of macroeconomic variables on suicide

2005 ◽  
Vol 36 (2) ◽  
pp. 181-189 ◽  
Author(s):  
MICHAEL BERK ◽  
SEETAL DODD ◽  
MARGARET HENRY
Keyword(s):  
Interest Rates ◽  
Consumer Price Index ◽  
Age Groups ◽  
Striking Difference ◽  
Range Data ◽  
Opposite Pattern ◽  
Male And Female ◽  
Suicide Rates ◽  
Age Related ◽  
Loan Interest Rates

Background. There are a large number of factors mediating suicide. Many studies have searched for a direct causal relationship between economic hardship and suicide, however, findings have been varied.Method. Suicide data was obtained from the Australian Bureau of Statistics for the period between January 1968 and August 2002. These were correlated with a suite of macroeconomic data including housing loan interest rates, unemployment rates, days lost to industrial disputes, Consumer Price Index, gross domestic product, and the Consumer Sentiment Index.Results. A total of 51845 males and 16327 females committed suicide between these dates. There were significant associations between suicide rates and eleven macroeconomic indicators for both genders in at least one age range. Data was divided into male and female and five age ranges and pooled ages. Analyses were conducted on these 132 datasets resulting in 80 significant findings. The data was generally stronger for indices measuring economic performance than indices measuring consumers' perceptions of the state of the economy. A striking difference between male and female trends was seen. Generally, male suicide rates increased with markers of economic adversity, while the opposite pattern was seen in females. There were significantly different patterns in age-stratified data, with for example higher housing loan interest rates having a positive association with suicide in younger people and a negative association in older age groups.Conclusion. Macroeconomic trends are significantly associated with suicide. The patterns in males and females are very different, and there are further substantial age-related differences.

Abstract 220: Transcriptional Analysis Of Caveolin And Cavin In The Male And Female Ageing Mouse Heart Following Ischemic Stress

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Can J Kiessling ◽  
Melissa Reichelt ◽  
John Headrick ◽  
Kevin Ashton
Keyword(s):  
G Protein ◽  
Ischemic Tolerance ◽  
Transcriptional Analysis ◽  
Membrane Microdomains ◽  
G Protein Coupled Receptor ◽  
Male And Female ◽  
Female Mice ◽  
Age Related ◽  
G Protein Coupled ◽  
Ischemic Stress

Cardioprotection against infarction and dysfunction in the myocardium involves G-protein-coupled receptor signalling orchestrated by specialised membrane microdomains termed caveolae. The caveolin protein family consist of three subtypes: caveolin-1, −2 and −3 (Cav1-3) and are responsible for the formation of caveolae and hypothesized to orchestrate cardioprotective signalling. Caveolin-3 deficiency and overexpression has been shown to attenuate and restore cardioprotection, respectively. Recently, a family of four related proteins known as cavins (Cavin1-4) have been implicated as regulators of caveolae formation and function. The roles and expression distribution of the cavin family is currently unknown in cardiac tissue. In this study hearts were isolated from 8, 16, 32 and 48 week male and female mice and subjected to normoxic perfusion (80 min) or ischemic stress (20 min global ischemia, 60 min reperfusion). RT-qPCR was used to assess differential gene expression of caveolin and cavin subtypes across these ages in both sexes. Decreased post-ischemic pressure development and increased LDH release were observed in 32 and 48 week old relative to 8 week old male hearts hearts, indicative of age-related loss of ischemic tolerance. Females showed greater tolerance to ischemia at 32 and 48 week old hearts when compared to male counterparts. In normoxic male 48 week old hearts, Cav1,-2,-3 and Cavin1 were significantly repressed, whilst post-ischemic male 48 week old hearts demonstrated significant repression of Cav3 and Cavin1 only. Normoxic female hearts showed no significant changes in caveolin and cavin transcript expression over the aging time course. However, post-ischemic female 48 week old hearts showing significant down-regulation of Cav3 only. Taken together, alterations in caveolin and cavin expression may contribute to the age-related loss of ischemic tolerance and G-protein-coupled receptor-mediated protection in aging male and female mice hearts.

scholarly journals The effect of smiling on the perceived age of male and female faces across the lifespan

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tzvi Ganel ◽  
Melvyn A. Goodale
Keyword(s):  
Young Adults ◽  
Age Groups ◽  
Aging Effect ◽  
Common Belief ◽  
Male And Female ◽  
Age Related ◽  
The Face ◽  
Series Of Experiments ◽  
Perceived Age ◽  
Middle Aged Adults

AbstractPrevious research has shown an unintuitive effect of facial expression on perceived age: smiling faces are perceived as older compared to neutral faces of the same people. The aging effect of smiling (AES), which is thought to result from the presence of smile-related wrinkles around the eyes, contradicts the common belief that smiling faces should be perceived as younger, not older. Previous research, however, has focused on faces of young adults, where the absence of inherent, age-related wrinkles and other age signs is offset by the weight of the smile-related wrinkles. In a series of experiments, we tested whether the AES extends to male and female faces in older age groups. We replicated the AES in young adults (20–39) and showed that it disappeared in older adults (60–79) of both genders. For photos of middle-aged adults (40–59), however, AES was found only for male, but not for female faces, who showed fewer and less prominent smile-related wrinkles. The results suggest that a person’s apparent age is perceived in a holistic manner in which age-related cues in the region of the eyes are weighted against age cues in other regions of the face.

scholarly journals SEX AND AGE-RELATED CHANGES IN PERFORMANCE IN THE DUATHLON WORLD CHAMPIONSHIPS

2020 ◽  
Vol 26 (3) ◽  
pp. 234-238
Author(s):  
Oscar Romero-Ramos ◽  
Emilio Fernández-Rodríguez ◽  
Daniel Mayorga-Vega ◽  
Rafael Merino-Marbán ◽  
Robert Podstawski
Keyword(s):  
Female Athletes ◽  
Age Groups ◽  
Performance Ratio ◽  
Age Group ◽  
Level Of Evidence ◽  
Male And Female ◽  
Professional Career ◽  
Age Related ◽  
And Performance ◽  
Retrospective Comparative Study

ABSTRACT Objective Our study analyses differences in performance between sexes, and changes in performance between age groups at Olympic distance during the ITU Duathlon World Championships, held between 2005 and 2016. During this period, a total of 9,772 duathletes were analysed (6,739 men and 3,033 women). Methods Two-way analyses of variance (ANOVA) were used to examine sex- and age-related differences in performance (time, percentage of time and performance ratio) in the first running and cycling legs, the second running leg, and total race for the top 10 male and female athletes in each age group at the Duathlon World Championships. Results The age group with the highest participation, in both male and female categories, was 40-44 years, and it was found that the mean age of female finisher participants across all age groups was 23.5±12. With regards to performance, the best results for total race time and the cycling segment were achieved in the 30-34-year age group, for both male and female athletes. With regards to performance in the first and third segments (running legs), the best times were achieved in the 25-29 and 30-34 age groups, for men and women respectively. Conclusion According to the results of our study, the best results in the professional career of a duathlete are achieved at between 30 and 35 years, therefore the athlete should incorporate this factor into their training plan. Level of evidence III; Retrospective comparative study.

scholarly journals Effects of hyperinsulinemia on pancreatic cancer development and the immune microenvironment revealed through single-cell transcriptomics

2021 ◽  
Author(s):  
Anni M.Y. Zhang ◽  
Twan J.J. de Winter ◽  
Su Wang ◽  
Stephane Flibotte ◽  
Yiwei Bernie Zhao ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Single Cell ◽  
Protein Translation ◽  
Cell Types ◽  
Insulin Production ◽  
Immune Microenvironment ◽  
Male And Female ◽  
Female Mice ◽  
Increased Risk ◽  
Multiple Cell

AbstractHyperinsulinemia is independently associated with increased risk and mortality of pancreatic cancer. We recently reported that a ∼50% reduction in pancreatic intraepithelial neoplasia (PanIN) pre-cancerous lesions in mice could be achieved with reduced insulin production. However, only female mice remained normoglycemic and only the gene dosage of rodent-specific Ins1 alleles was tested in our previous model. Moreover, we did not delve into the molecular and cellular mechanisms associated with modulating hyperinsulinemia. Here, we studied PanIN lesion development in both male and female Ptf1aCreER;KrasLSL-G12D mice lacking the rodent specific Ins1 gene, and possessing one or two alleles of the wild-type Ins2 gene to modulate insulin production. High-fat diet induced hyperinsulinemia was transiently and modestly reduced, without affecting glucose tolerance, in male and female mice with only one allele of Ins2. Genetic reduction of insulin production resulted in mice with a tendency for less PanIN and acinar-to-ductal metaplasia (ADM) lesions. Using single-cell transcriptomics, we found hyperinsulinemia affected multiple cell types in the pancreas, with the most statistically significant effects on local immune cell populations, which were highly represented in our analysis. Specifically, hyperinsulinemia modulated pathways associated with protein translation, MAPK-ERK signaling, and PI3K-AKT signaling, which were changed in epithelial cells and subsets of immune cells. These data suggest a role for the immune microenvironment in hyperinsulinemia-driven PanIN development. Together with our previous work, we propose that mild suppression of insulin levels may be useful in preventing pancreatic cancer by acting on multiple cell types.

scholarly journals AGE AND GENDER RELATED MORTALITY AND OUTCOME OF COVID 19 POSITIVE PATIENTS

2021 ◽  
Vol 9 (12) ◽  
pp. 696-702
Author(s):  
Suhail Mansoor ◽  
◽  
Ghulam Jeelani Romshoo ◽  
Abroo Bashir ◽  
◽  
...  
Keyword(s):  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Age Groups ◽  
Care Hospital ◽  
Age Group ◽  
Age And Gender ◽  
Male And Female ◽  
Age Related ◽  
And Gender ◽  
Related Mortality

Background: This study was aimed to evaluate the age and gender related mortality and outcome of covid 19 positive patients in order to further strengthen the management of covid 19 patients as the insights from these data will be useful in determining preventive measures and treatment policies of covid 19 patients. Methodology: This was a retrospective observational study done in adult covid positive patients admitted in Tertiary Care Hospital from first May 2020 to 30 June 2021.The age related mortality and outcome in these patients was analyzed. Results: A total of 816 adult covid -19 positive patients were admitted in a Tertiary care hospital,GMC Anantnag from May 2020 to June 2021. Among the patients, 53.55 % were males and 46.44 % were females. The mean of the age involved was 57.96 years. The most common presenting symptom was fever (85%) followed by cough (70%) and shortness of breath (40%). Approximately 20% of patients presented with nonspecific complaints (including generalized aches, pains, body aches, myalgias etc). All age groups were affected equally (29% in 15-50yr, 37% in 51-65yr, 33% in 66-100yr). Maximum patients (70% ) affected were more than 50 yr of age. About 73.4% were discharged, 6% were reffered, 20% expired. So, overall hospital mortality was 20%. Further, Maximum (86%) of covid positive patients expired in age group of above 50 yrs. Further, Male and Female Mortality was also same in covid positive patients. Conclusion: Males and females were affected equally by Covid -19 disease with no sex predilection.. Fever was the main presenting symptom. All age groups were affected equally but mortality was more in elderly age group. Further, mortality is same in male and female covid positive patients with no gender predilection.

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