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The VEGF/VEGFR Axis Revisited: Implications for Cancer Therapy
The vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) axis is indispensable in the process of angiogenesis and has been implicated as a key driver of tumor vascularization. Consequently, several strategies that target VEGF and its cognate receptors, VEGFR-1 and VEGFR-2, have been designed to treat cancer. While therapies targeting full-length VEGF have resulted in an improvement in both overall survival and progression-free survival in various cancers, these benefits have been modest. In addition, the inhibition of VEGFRs is associated with undesirable off-target effects. Moreover, VEGF splice variants that modulate sprouting and non-sprouting angiogenesis have been identified in recent years. Cues within the tumor microenvironment determine the expression patterns of these variants. Noteworthy is that the mechanisms of action of these variants challenge the established norm of VEGF signaling. Furthermore, the aberrant expression of some of these variants has been observed in several cancers. Herein, developments in the understanding of the VEGF/VEGFR axis and the splice products of these molecules, as well as the environmental cues that regulate these variants are reviewed. Furthermore, strategies that incorporate the targeting of VEGF variants to enhance the effectiveness of antiangiogenic therapies in the clinical setting are discussed.
Journal Article
“Men are the head of the family, the dominant head”: A mixed method study of male involvement in maternal and child health in a patriarchal setting, Western Nigeria
The importance of involving men in reproductive, maternal and child health (RMCH) programs is increasingly recognized globally. In Nigeria, most MCH services do not actively engage fathers.
To assess men's knowledge, involvement in MCH and the barriers in Southwest Nigeria. Predictors of good knowledge and involvement were also assessed.
This was a community-based cross sectional study. Quantitative and qualitative methods were used in data collection which was done within a period of three months in 2018. Quantitative data were collected with interviewer administered questionnaires from 418 respondents who were selected by multistage sampling methodology. The topic was further explored using focus group discussion (FGD). Quantitative data were analysed using EPI-INFO version 7. Quantitative variables were summarized using means and standard deviations while multivariable analysis was carried out to determine predictors of good knowledge and involvement in MCH. A combination of deductive and inductive analysis was used for the qualitative data.
Overall, 65% of men had good knowledge of MCH while 60.8% had good involvement. Predictors of good knowledge were being a Christian (AOR 1.674, 95% CI 1.045-2.679), being of Yoruba tribe (AOR 1.753, 95% CI 1.100-2.796), having post-secondary education (AOR 1.984, 95% CI 1.002-3.928), having more under-fives in the household (AOR 2.162 95% CI 1.365-3.425) and spouse having post-secondary education (AOR 2.755, 95% CI 1.189-6.382). Predictors of good involvement in MCH include higher educational level of spouse: secondary (AOR 2.852, 95% CI 1.214-6.699), post-secondary (AOR 2.270, 95% CI 1.000-5.161) and having good knowledge of MCH (AOR 2.518, 95% CI 1.587-3.994). From the FGD, other factors which influence involvement were related to traditional/cultural orientation, time constraint and finance among others.
Men's knowledge and their involvement in maternal and child health were sub-optimal. For improvement, community-based intervention programmes should be designed for men and implemented, taking into consideration their traditional/cultural roles, religious orientation, busy schedules, and educational backgrounds. They should be re-oriented on their patriarchally informed belief about their perceived roles in RMCH.
Journal Article
The role of itaconate in host defense and inflammation
Macrophages exposed to inflammatory stimuli including LPS undergo metabolic reprogramming to facilitate macrophage effector function. This metabolic reprogramming supports phagocytic function, cytokine release, and ROS production that are critical to protective inflammatory responses. The Krebs cycle is a central metabolic pathway within all mammalian cell types. In activated macrophages, distinct breaks in the Krebs cycle regulate macrophage effector function through the accumulation of several metabolites that were recently shown to have signaling roles in immunity. One metabolite that accumulates in macrophages because of the disturbance in the Krebs cycle is itaconate, which is derived from cis-aconitate by the enzyme cis-aconitate decarboxylase (ACOD1), encoded by immunoresponsive gene 1 (Irg1). This Review focuses on itaconate's emergence as a key immunometabolite with diverse roles in immunity and inflammation. These roles include inhibition of succinate dehydrogenase (which controls levels of succinate, a metabolite with multiple roles in inflammation), inhibition of glycolysis at multiple levels (which will limit inflammation), activation of the antiinflammatory transcription factors Nrf2 and ATF3, and inhibition of the NLRP3 inflammasome. Itaconate and its derivatives have antiinflammatory effects in preclinical models of sepsis, viral infections, psoriasis, gout, ischemia/reperfusion injury, and pulmonary fibrosis, pointing to possible itaconate-based therapeutics for a range of inflammatory diseases. This intriguing metabolite continues to yield fascinating insights into the role of metabolic reprogramming in host defense and inflammation.
Journal Article
Mediating Effects of Parental Stress on Harsh Parenting and Parent-Child Relationship during Coronavirus (COVID-19) Pandemic in Singapore
Because of the Coronavirus (COVID-19) pandemic, “Circuit-breaker” safety distancing was implemented in Singapore from April to May 2020. Schools and workplaces were closed and parents had to balance telecommuting with parenting responsibilities. Coupled with the high degree of economic uncertainty and reduced social support, these circumstances are hypothesized to increase parenting stress. Based on the Parental Stress Model, this study aims to understand how parents’ perceived impact of COVID-19 increased harsh parenting and reduced parent-child relationship closeness through the mediating effects of parenting stress. We collected data from 258 parents living in Singapore using online surveys disseminated through Facebook and community organizations. Our predictor was the perceived impact of COVID-19. Parental stress (mediator) was measured with the Parental Stress Scale. Two outcomes were used: parent-child relationship closeness and harsh parenting (spanking, yelling). Using mediation analysis in the SEM framework, we tested the indirect effects using bias-corrected bootstrap confidence intervals. Our results indicated that parenting stress was a significant mediator in the relationship between the perceived impact of COVID-19 and (a) parent-child closeness (indirect effect = −.30, Bootstrap 99% CI[−.59, −.11]) and (b) harsh parenting (indirect effect = .58, Bootstrap 99% CI[.25, .94]). The impact of COVID-19 and stay-home orders can increase parenting stress. This, in turn, has a negative impact on parenting by affecting parents’ relationship with their children and increasing the use of harsh parenting. Given that these are risk factors for potential child abuse, supporting parents and mitigating the impact of COVID-19 are important.
Journal Article
‘God helps those who help themselves’… religion and Assisted Reproductive Technology usage amongst urban Ghanaians
Assisted Reproductive Technology (ART) is increasingly becoming a viable option for infertile couples in Ghana. There exists significant literature that explores the gender, legal, religious and socio-cultural implications of ART usage. In this paper, we expand the discourse on the nexus between religion and ART usage by looking at how the former is used as a frame of reference in the decision-making process, as well as how it is employed to explain treatment successes and failures. Irrespective of religious orientation, there was a general acceptance of ART by participants in the study-with exceptions only when it came to some aspects of the procedure. Even here, participants’ desperate desire to have children, tended to engender some accommodation of procedures they were uncomfortable with because of their religious beliefs. Thus, in contrast to some studies that suggest religion as interfering with ART use, we posit that religion is not an inhibiting factor to ART usage. On the contrary, it is an enabling factor, engendering the agentic attitude of participants to find a solution to their infertility in ART; as well as providing the strength to endure the physical and emotional discomfort associated with the biomedical process of conception and childbirth. In this context, religion thus provides participants with a frame of reference to navigate the spaces between decision-making, treatment processes and outcomes, and attributions of responsibility for the outcomes whatever they may be.
Journal Article