Microglia,which comprise approximately 10%of total cells in the brain,are the resident immune cells in the central nervous system and contribute to maintaining the brain homeostasis through monitoring their microenvir...Microglia,which comprise approximately 10%of total cells in the brain,are the resident immune cells in the central nervous system and contribute to maintaining the brain homeostasis through monitoring their microenvironment(Kettenmann et al.,2011).Recent studies have reported that microglia also regulate neural circuit formation after birth.The functional transition in microglia has been considered to correlate with their morphological changes over time.展开更多
Introduction<span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">: <span style="font-family:Verdana;">...Introduction<span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">: <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">In August 2014, the Yazidi community of Sinjar, in the Nineveh Governorate of Northern Iraq, was brutally targeted by the so-called Islamic State of Iraq and Syria (ISIS) for annihilation through murder, torture, and the systematic and premeditated use of rape and sexual slavery of Yazidi women. In 2016, the United Nations High Commissioner for Human Rights concluded that ISIS was committing genocide, crimes against humanity, and war crimes against Yazidis. Methods<span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">: <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Using current international literature, which includes reviews, qualitative interviews of survivors, and reports from medical and humanitarian actors, this paper explores the short and potentially long-term physical and mental health consequences of the extreme physical and sexual violence and atrocities perpetrated against Yazidi women.<span style="font-family:""> <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Results<span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">: <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Yazidi women survivors of kidnapping, sex slavery, and rape experienced significant levels of physical ailments, chronic pain, and mental health conditions. All women reported feelings of guilt, stress, insomnia, and severe flashbacks. The incidence of post-traumatic stress disorder (PTSD) ranged from 42% to 90%. Sixty-seven percent suffered from a somatoform disorder, 53% had depression, 39% experienced anxiety, and 28% suffered from dissociation.<span style="font-family:""> <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Conclusions<span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">: <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Sexual violence against women is a common tool systematically employed during wars and genocide. In recent ISIS attacks, intentional perpetration of mass rapes of women and execution of men was a strategy to destroy an entire population. PTSD and depression are common after traumatic stress. For disaster responders and humanitarian workers, training and education to understand, try to prevent, and plan for interventions when gender-based violence and sexual exploitation occurs must become a mandatory part of emergency preparedness.展开更多
Hevin/Sparcl1(hereafter referred to as Hevin)is an extracellular matrix protein encoded by the SPARCL1 gene.Recently,it has been revealed that Hevin has various functions,such as synapse formation,neuronal migration,i...Hevin/Sparcl1(hereafter referred to as Hevin)is an extracellular matrix protein encoded by the SPARCL1 gene.Recently,it has been revealed that Hevin has various functions,such as synapse formation,neuronal migration,inflammation,and angiogenesis(Gongidi et al.,2004;Naschberger et al.,2016;Singh et al.,2016;Liu et al.,2021).In addition,genome-wide association studies uncovered de novo and familial mutations of the SPARCL1 gene associated with a risk for autism spectrum disorder(ASD)(De Rubeis et al.,2014).However,the relationship between ASD-associated Hevin mutant and cellular phenotype has not been clarified.Recently,we have reported that ASD-associated mutation in Hevin reduces secretion efficiency and induces endoplasmic reticulum(ER)stress caused by structural instability(Taketomi et al.,2022).In this perspective,we discuss the relationship between the molecular functions of Hevin and ASD risk(Figure 1A).Also,we introduce our recent findings that link ASD-associated Hevin mutant to the cellular phenotype of ASD.展开更多
Microglia are the resident immune cells of the central nervous system （CNS）, In the normal state, microglia have a ramified shape and con- tinuously survey the conditions of the brain.
Resistance to ferroptosis,a form of regulated cell death caused by disruptions in iron ion and intracellular redox homeostasis,is closely related to tumorigenesis and tumor drug resistance;therefore,targeting ferropto...Resistance to ferroptosis,a form of regulated cell death caused by disruptions in iron ion and intracellular redox homeostasis,is closely related to tumorigenesis and tumor drug resistance;therefore,targeting ferroptosis-related pathways has garnered attention as a potential antitumor therapeutic strategy.However,the molecular mechanisms underlying ferroptosis resistance in tumor cells remain unknown.Zinc-finger estrogen receptor interaction clone 6(ZER6)consists of two isoforms with distinct N-termini,p52-ZER6 and p71-ZER6.ZER6 is upregulated in tumors and promotes tumorigenic potential;however,whether ZER6 is involved in tumor cell ferroptosis resistance remains unknown.Herein,we identified p52-ZER6 as a novel regulator of tumor cell ferroptosis resistance.p52-ZER6 promotes the transcriptional activity of DAZAP1,an RNA-binding protein.DAZAP1,in turn,enhances the stability of SLC7A11 mRNA by binding to its 30-UTR region,thereby increasing SLC7A11 expression and cellular glutathione levels.This subsequently reduces lipid peroxide accumulation and enhances tumor cell ferroptosis resistance,eventually promoting tumorigenic potential.These findings reveal a new function of p52-ZER6 in regulating SLC7A11 mRNA stability via DAZAP1,ultimately leading to ferroptosis resistance and tumorigenic potential.Additionally,we also suggest targeting p52-ZER6 as a potential strategy to promote the efficacy of ferroptosis-based antitumor therapies.展开更多
文摘Microglia,which comprise approximately 10%of total cells in the brain,are the resident immune cells in the central nervous system and contribute to maintaining the brain homeostasis through monitoring their microenvironment(Kettenmann et al.,2011).Recent studies have reported that microglia also regulate neural circuit formation after birth.The functional transition in microglia has been considered to correlate with their morphological changes over time.
文摘Introduction<span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">: <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">In August 2014, the Yazidi community of Sinjar, in the Nineveh Governorate of Northern Iraq, was brutally targeted by the so-called Islamic State of Iraq and Syria (ISIS) for annihilation through murder, torture, and the systematic and premeditated use of rape and sexual slavery of Yazidi women. In 2016, the United Nations High Commissioner for Human Rights concluded that ISIS was committing genocide, crimes against humanity, and war crimes against Yazidis. Methods<span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">: <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Using current international literature, which includes reviews, qualitative interviews of survivors, and reports from medical and humanitarian actors, this paper explores the short and potentially long-term physical and mental health consequences of the extreme physical and sexual violence and atrocities perpetrated against Yazidi women.<span style="font-family:""> <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Results<span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">: <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Yazidi women survivors of kidnapping, sex slavery, and rape experienced significant levels of physical ailments, chronic pain, and mental health conditions. All women reported feelings of guilt, stress, insomnia, and severe flashbacks. The incidence of post-traumatic stress disorder (PTSD) ranged from 42% to 90%. Sixty-seven percent suffered from a somatoform disorder, 53% had depression, 39% experienced anxiety, and 28% suffered from dissociation.<span style="font-family:""> <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Conclusions<span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">: <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Sexual violence against women is a common tool systematically employed during wars and genocide. In recent ISIS attacks, intentional perpetration of mass rapes of women and execution of men was a strategy to destroy an entire population. PTSD and depression are common after traumatic stress. For disaster responders and humanitarian workers, training and education to understand, try to prevent, and plan for interventions when gender-based violence and sexual exploitation occurs must become a mandatory part of emergency preparedness.
文摘Hevin/Sparcl1(hereafter referred to as Hevin)is an extracellular matrix protein encoded by the SPARCL1 gene.Recently,it has been revealed that Hevin has various functions,such as synapse formation,neuronal migration,inflammation,and angiogenesis(Gongidi et al.,2004;Naschberger et al.,2016;Singh et al.,2016;Liu et al.,2021).In addition,genome-wide association studies uncovered de novo and familial mutations of the SPARCL1 gene associated with a risk for autism spectrum disorder(ASD)(De Rubeis et al.,2014).However,the relationship between ASD-associated Hevin mutant and cellular phenotype has not been clarified.Recently,we have reported that ASD-associated mutation in Hevin reduces secretion efficiency and induces endoplasmic reticulum(ER)stress caused by structural instability(Taketomi et al.,2022).In this perspective,we discuss the relationship between the molecular functions of Hevin and ASD risk(Figure 1A).Also,we introduce our recent findings that link ASD-associated Hevin mutant to the cellular phenotype of ASD.
文摘Microglia are the resident immune cells of the central nervous system （CNS）, In the normal state, microglia have a ramified shape and con- tinuously survey the conditions of the brain.
基金supported by grants from the National Natural Science Foundation of China(82372655,82173029,32270778,and 32070715)the Natural Science Foundation of Chongqing(CSTB2022NSCQ-MSX0611 and CSTB2022NSCQ-MSX0612,China).
文摘Resistance to ferroptosis,a form of regulated cell death caused by disruptions in iron ion and intracellular redox homeostasis,is closely related to tumorigenesis and tumor drug resistance;therefore,targeting ferroptosis-related pathways has garnered attention as a potential antitumor therapeutic strategy.However,the molecular mechanisms underlying ferroptosis resistance in tumor cells remain unknown.Zinc-finger estrogen receptor interaction clone 6(ZER6)consists of two isoforms with distinct N-termini,p52-ZER6 and p71-ZER6.ZER6 is upregulated in tumors and promotes tumorigenic potential;however,whether ZER6 is involved in tumor cell ferroptosis resistance remains unknown.Herein,we identified p52-ZER6 as a novel regulator of tumor cell ferroptosis resistance.p52-ZER6 promotes the transcriptional activity of DAZAP1,an RNA-binding protein.DAZAP1,in turn,enhances the stability of SLC7A11 mRNA by binding to its 30-UTR region,thereby increasing SLC7A11 expression and cellular glutathione levels.This subsequently reduces lipid peroxide accumulation and enhances tumor cell ferroptosis resistance,eventually promoting tumorigenic potential.These findings reveal a new function of p52-ZER6 in regulating SLC7A11 mRNA stability via DAZAP1,ultimately leading to ferroptosis resistance and tumorigenic potential.Additionally,we also suggest targeting p52-ZER6 as a potential strategy to promote the efficacy of ferroptosis-based antitumor therapies.
