Pub Date : 2018-12-31DOI: 10.5772/INTECHOPEN.83447
Laura C. Twomey, R. Wallace, Marco Mangone, BernardDegryse, S. Sheridan, M. Harrison, N. Moyna, Gerardene Meade-Murphy, N. Navasiolava, Marc-AntoineCustaud, Ronan P. Murphy
Cardiovascular disease (CVD) risk factors can be classed as modifiable or non-modifiable. Physical inactivity and obesity represent major behavioural risk factors for the initiation, development and progression of CVD. Platelet dysfunction is pivotal to the aetiology of CVD, a chronic vascular inflammatory condition, which is characterised by a lag time between onset and clinical manifestation. This indicates the role of epigenetic drift, defined by stochastic patterns of gene expression not dependent on dynamic changes in coding DNA. The epigenome, a collection of chemical marks on DNA and histones, is established during embryogenesis and modified by age and lifestyle. Biogenesis and effector function of non-coding RNA, such as microRNA, play a regulatory role in gene expression and thus the epigenetic mechanism. In this chapter, we will focus on the effect of the modifiable risk factors of physical activity/inactivity and overweight/obesity on platelet function, via epigenetic changes in both megakaryocytopoiesis and thrombopoiesis. We will also discuss the role of acute exercise on platelet function and the impact of cardiorespiratory fitness (CRF) on platelet responses to acute exercise. This chapter will highlight the potential role of platelets as circulating functional biomarkers of epigenetic drift to implement, optimise and monitor CVD preventive management strategies.
{"title":"Platelets: Functional Biomarkers of Epigenetic Drift","authors":"Laura C. Twomey, R. Wallace, Marco Mangone, BernardDegryse, S. Sheridan, M. Harrison, N. Moyna, Gerardene Meade-Murphy, N. Navasiolava, Marc-AntoineCustaud, Ronan P. Murphy","doi":"10.5772/INTECHOPEN.83447","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.83447","url":null,"abstract":"Cardiovascular disease (CVD) risk factors can be classed as modifiable or non-modifiable. Physical inactivity and obesity represent major behavioural risk factors for the initiation, development and progression of CVD. Platelet dysfunction is pivotal to the aetiology of CVD, a chronic vascular inflammatory condition, which is characterised by a lag time between onset and clinical manifestation. This indicates the role of epigenetic drift, defined by stochastic patterns of gene expression not dependent on dynamic changes in coding DNA. The epigenome, a collection of chemical marks on DNA and histones, is established during embryogenesis and modified by age and lifestyle. Biogenesis and effector function of non-coding RNA, such as microRNA, play a regulatory role in gene expression and thus the epigenetic mechanism. In this chapter, we will focus on the effect of the modifiable risk factors of physical activity/inactivity and overweight/obesity on platelet function, via epigenetic changes in both megakaryocytopoiesis and thrombopoiesis. We will also discuss the role of acute exercise on platelet function and the impact of cardiorespiratory fitness (CRF) on platelet responses to acute exercise. This chapter will highlight the potential role of platelets as circulating functional biomarkers of epigenetic drift to implement, optimise and monitor CVD preventive management strategies.","PeriodicalId":286564,"journal":{"name":"Homeostasis - An Integrated Vision","volume":"12 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123760896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-12-29DOI: 10.5772/INTECHOPEN.80924
Laura C. Twomey, Robert G. Wallace, Philip M. Cummins, B. Degryse, S. Sheridan, M. Harrison, N. Moyna, Gerardene Meade-Murphy, N. Navasiolava, M. Custaud, Ronan P. Murphy
Platelets are small, anucleate cells that travel as resting discoid fragments in the circulation. Their average circulating life span is 8–9 days, and their formation is an elegant and finely orchestrated series of cellular processes known as megakaryocytopoiesis and thrombopoiesis. This involves the commitment of haematopoietic stem cells, proliferation, terminal differentiation of megakaryocytic progenitors and maturation of megakaryocytes to produce functional platelets. This complex process occurs in specialised endosteal and vascular niches in the bone marrow where megakaryocytes form proplatelet projections, releasing platelets into the circulation. Upon contact with an injured blood vessel, they prevent blood loss through processes of adhesion, activation and aggregation. Platelets play a central role in cardiovascular disease (CVD), both in the development of atherosclerosis and as the cellular mediator in the development of thrombosis. Platelets have diverse roles not limited to thrombosis/haemostasis, also being involved in many vascular inflammatory conditions. Depending on the physiological context, platelet functions may be protective or contribute to adverse thrombotic and inflammatory outcomes. In this chapter, we will discuss platelets in context of their formation and function. Because of their multifaceted role in maintaining physiological homeostasis, current and development of platelet function testing platforms will be discussed.
{"title":"Platelets: From Formation to Function","authors":"Laura C. Twomey, Robert G. Wallace, Philip M. Cummins, B. Degryse, S. Sheridan, M. Harrison, N. Moyna, Gerardene Meade-Murphy, N. Navasiolava, M. Custaud, Ronan P. Murphy","doi":"10.5772/INTECHOPEN.80924","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.80924","url":null,"abstract":"Platelets are small, anucleate cells that travel as resting discoid fragments in the circulation. Their average circulating life span is 8–9 days, and their formation is an elegant and finely orchestrated series of cellular processes known as megakaryocytopoiesis and thrombopoiesis. This involves the commitment of haematopoietic stem cells, proliferation, terminal differentiation of megakaryocytic progenitors and maturation of megakaryocytes to produce functional platelets. This complex process occurs in specialised endosteal and vascular niches in the bone marrow where megakaryocytes form proplatelet projections, releasing platelets into the circulation. Upon contact with an injured blood vessel, they prevent blood loss through processes of adhesion, activation and aggregation. Platelets play a central role in cardiovascular disease (CVD), both in the development of atherosclerosis and as the cellular mediator in the development of thrombosis. Platelets have diverse roles not limited to thrombosis/haemostasis, also being involved in many vascular inflammatory conditions. Depending on the physiological context, platelet functions may be protective or contribute to adverse thrombotic and inflammatory outcomes. In this chapter, we will discuss platelets in context of their formation and function. Because of their multifaceted role in maintaining physiological homeostasis, current and development of platelet function testing platforms will be discussed.","PeriodicalId":286564,"journal":{"name":"Homeostasis - An Integrated Vision","volume":"126 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127968392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-11-05DOI: 10.5772/INTECHOPEN.76229
K. Nagashima, K. Tokizawa, Shuri Marui, Y. Uchida
We have revealed that circadian body temperature (T b ) rhythm is significantly influenced by fasting/fasting-related hormones. The effect of circadian mechanism and fasting/fast -ing-related hormones on thermoregulation was examined. Fasting decreases T b during the light phase in rodents. For the regulation, the suprachiasmatic nucleus (SCN) and clock genes, such as Cry and Clock , are necessary. In addition, ghrelin and several hypothalamic nuclei, that is, the medial preoptic area, paraventricular nucleus (PVN), and arcuate nucleus (ARC), play a key role in the T b rhythm. During the light phase, fasting and ghrelin affect the hypothalamic areas. The activity of the SCN increases and that of the ARC decreases. The SCN sends inhibitory signals to the PVN, which may result in a lower heat production in the interscapular brown adipose tissue (iBAT) and T b . By contrast, during the dark phase, the activity of the SCN decreases and that of the ARC increases. The inhibitory signal from the SCN is less, and the PVN is activated. Heat production of the iBAT increases and T b is maintained. There are functional and anatomical connections between the circadian and thermoregulation systems. The circadian system modulates thermoregulatory response to hypothermia and/or cold depending on time and feeding condition. same peak phases during the LD conditions. As for the T b and V ˙ O 2 rhythms in the LD condition, the daily means were lower, and the amplitudes of the rhythms were higher in the food-restriction condition than those under the ad lib feeding condition. The study showed that the circadian T b rhythm is observed even in mice that lack the internal circadian mechanism, when an external lighting and feeding stimuli that alter heat production are observed. The result showed that the heat production rhythm may be a key component for the T b rhythm.
{"title":"Circadian Body Temperature Rhythm and the Interaction with Energy State","authors":"K. Nagashima, K. Tokizawa, Shuri Marui, Y. Uchida","doi":"10.5772/INTECHOPEN.76229","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.76229","url":null,"abstract":"We have revealed that circadian body temperature (T b ) rhythm is significantly influenced by fasting/fasting-related hormones. The effect of circadian mechanism and fasting/fast -ing-related hormones on thermoregulation was examined. Fasting decreases T b during the light phase in rodents. For the regulation, the suprachiasmatic nucleus (SCN) and clock genes, such as Cry and Clock , are necessary. In addition, ghrelin and several hypothalamic nuclei, that is, the medial preoptic area, paraventricular nucleus (PVN), and arcuate nucleus (ARC), play a key role in the T b rhythm. During the light phase, fasting and ghrelin affect the hypothalamic areas. The activity of the SCN increases and that of the ARC decreases. The SCN sends inhibitory signals to the PVN, which may result in a lower heat production in the interscapular brown adipose tissue (iBAT) and T b . By contrast, during the dark phase, the activity of the SCN decreases and that of the ARC increases. The inhibitory signal from the SCN is less, and the PVN is activated. Heat production of the iBAT increases and T b is maintained. There are functional and anatomical connections between the circadian and thermoregulation systems. The circadian system modulates thermoregulatory response to hypothermia and/or cold depending on time and feeding condition. same peak phases during the LD conditions. As for the T b and V ˙ O 2 rhythms in the LD condition, the daily means were lower, and the amplitudes of the rhythms were higher in the food-restriction condition than those under the ad lib feeding condition. The study showed that the circadian T b rhythm is observed even in mice that lack the internal circadian mechanism, when an external lighting and feeding stimuli that alter heat production are observed. The result showed that the heat production rhythm may be a key component for the T b rhythm.","PeriodicalId":286564,"journal":{"name":"Homeostasis - An Integrated Vision","volume":"6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124334329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-11-05DOI: 10.5772/INTECHOPEN.76096
R. Mydin, Simon I Okekpa
Redox homeostasis is attained by the cautious regulation of both reactive oxygen species (ROS) formation and removal from the body system. A shift in ROS balance promotes oxidative injury and tumour development by inflicting damage to DNA and inducing inconsistencies in the genome. The sources of endogenous ROS in a cell include mETC, NOX, LOX, cytochrome P450 and XO. The exogenous risk factors of ROS are pollutants, chemicals/drugs, radiation and heavy metals. Oxidative phosphorylation in the mitochondria produces ROS with unpaired electrons. Superoxide anion is the major ROS produced in the human mitochondria. Bulk of the ROS generation in the mitochondria occurs at the electron transport chain as derivatives of respiration. Cancer cells sustain ROS production by suppressing the antioxidant-generation system. Balance between ROS production and subsequent detoxification is regulated by scavenging enzymes and antioxidant agents. Failure in sirtuin-3 (SIRT3), ATM and p53 activities elevates the intracellular levels of ROS. PKC α induces the expression of NOX (DUOX) during cancer development and the consequent increase in ROS production. The PI3K/AKT signalling pathway activates NOX with consequent ROS production and subsequent induction of instability in the genome, leading to cancer. In conclusion, the interruption of the redox pathways that regulate ROS and its redox signalling activities affects cell physiology and can ultimately result in abnormal signalling, uncontrolled oxidative impairment and tumorigenesis.
{"title":"Reactive Oxygen Species, Cellular Redox Homeostasis and Cancer","authors":"R. Mydin, Simon I Okekpa","doi":"10.5772/INTECHOPEN.76096","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.76096","url":null,"abstract":"Redox homeostasis is attained by the cautious regulation of both reactive oxygen species (ROS) formation and removal from the body system. A shift in ROS balance promotes oxidative injury and tumour development by inflicting damage to DNA and inducing inconsistencies in the genome. The sources of endogenous ROS in a cell include mETC, NOX, LOX, cytochrome P450 and XO. The exogenous risk factors of ROS are pollutants, chemicals/drugs, radiation and heavy metals. Oxidative phosphorylation in the mitochondria produces ROS with unpaired electrons. Superoxide anion is the major ROS produced in the human mitochondria. Bulk of the ROS generation in the mitochondria occurs at the electron transport chain as derivatives of respiration. Cancer cells sustain ROS production by suppressing the antioxidant-generation system. Balance between ROS production and subsequent detoxification is regulated by scavenging enzymes and antioxidant agents. Failure in sirtuin-3 (SIRT3), ATM and p53 activities elevates the intracellular levels of ROS. PKC α induces the expression of NOX (DUOX) during cancer development and the consequent increase in ROS production. The PI3K/AKT signalling pathway activates NOX with consequent ROS production and subsequent induction of instability in the genome, leading to cancer. In conclusion, the interruption of the redox pathways that regulate ROS and its redox signalling activities affects cell physiology and can ultimately result in abnormal signalling, uncontrolled oxidative impairment and tumorigenesis.","PeriodicalId":286564,"journal":{"name":"Homeostasis - An Integrated Vision","volume":"93 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116199495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-11-05DOI: 10.5772/INTECHOPEN.75209
S. T. Majeed, Rabiya Majeed, G. Shah, Khurshid IAndrabi
S6 kinase, a member of AGC family of protein kinases and a downstream effector of mTORC1 pathway has over the years found much relevance in maintaining a normal cel lular state by virtue of its established role in regulation of cell growth and proliferation. S6 kinase activity has been linked to different cellular processes like glucose homeostasis, translational and transcriptional regulation. Hence any dysregulation in S6K1 leads to the emergence of various pathological conditions like diabetes, cancer and obesity. It is as such S6 kinase has emerged as a potential target for therapeutic interventions employed in curing such diseases. The Present Chapter reviews the regulation of S6K1, its struc tural organization and functions, besides highlighting its potential to act as an alternative therapeutic target for various cancerous situations exhibiting deranged mTOR signaling so as to overcome the possibility of relapses observed otherwise while using conven - tional drugs
{"title":"S6 Kinase: A Compelling Prospect for Therapeutic Interventions","authors":"S. T. Majeed, Rabiya Majeed, G. Shah, Khurshid IAndrabi","doi":"10.5772/INTECHOPEN.75209","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.75209","url":null,"abstract":"S6 kinase, a member of AGC family of protein kinases and a downstream effector of mTORC1 pathway has over the years found much relevance in maintaining a normal cel lular state by virtue of its established role in regulation of cell growth and proliferation. S6 kinase activity has been linked to different cellular processes like glucose homeostasis, translational and transcriptional regulation. Hence any dysregulation in S6K1 leads to the emergence of various pathological conditions like diabetes, cancer and obesity. It is as such S6 kinase has emerged as a potential target for therapeutic interventions employed in curing such diseases. The Present Chapter reviews the regulation of S6K1, its struc tural organization and functions, besides highlighting its potential to act as an alternative therapeutic target for various cancerous situations exhibiting deranged mTOR signaling so as to overcome the possibility of relapses observed otherwise while using conven - tional drugs","PeriodicalId":286564,"journal":{"name":"Homeostasis - An Integrated Vision","volume":"243 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122912451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-11-05DOI: 10.5772/INTECHOPEN.77112
D. Kamimura, Yuki Tanaka, Takuto Ohki, Masaaki Murakami
Homeostasis of the central nervous system (CNS) is strictly regulated by a unique struc- ture of blood vessels, the blood-brain barrier (BBB). Experimental and clinical evidence has revealed that abnormalities in the BBB in chronic inflammatory diseases such as mul - tiple sclerosis (MS). By using an animal model of MS, we identified novel neuro-immune crosstalk to explain how pathogenic immune cells enter the CNS to disrupt its homeosta- sis, a phenomenon we named the gateway reflex. Regional neural inputs such as grav ity, electricity, pain or chronic stress cause specific neural activation to create a gateway of immune cells, particularly pathogenic ones, at specific blood vessels. Moreover, the recently discovered stress-induced gateway reflex uncovered a stress-induced neural link between the brain, gastrointestine, and heart. Thus, the gateway reflex is critical for the homeostasis of various organs, and aberrant activation of neural pathways by the gateway reflex disrupts normal organ homeostasis. The inflammatory reflex is another mechanism for local neuro-immune interactions. It potently exerts a cholinergic anti- inflammatory effect on various disease conditions. In this section, we discuss emerging roles for local neuro-immune interactions, with a special focus on the gateway reflex. sympathetic ganglion (4) and induces the activation of sympathetic nerves (5), which results in norepinephrine (NE) secretion (6) at the L5 dorsal vessels. NE enhances the inflammation amplifier in the L5 dorsal vessels, causing an upregulation of chemokines and recruiting pathogenic CD4+ T cells from the vessels (7).
{"title":"Gateway Reflex: A Neuro-Immune Crosstalk for Organ-Specific Disease Development","authors":"D. Kamimura, Yuki Tanaka, Takuto Ohki, Masaaki Murakami","doi":"10.5772/INTECHOPEN.77112","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.77112","url":null,"abstract":"Homeostasis of the central nervous system (CNS) is strictly regulated by a unique struc- ture of blood vessels, the blood-brain barrier (BBB). Experimental and clinical evidence has revealed that abnormalities in the BBB in chronic inflammatory diseases such as mul - tiple sclerosis (MS). By using an animal model of MS, we identified novel neuro-immune crosstalk to explain how pathogenic immune cells enter the CNS to disrupt its homeosta- sis, a phenomenon we named the gateway reflex. Regional neural inputs such as grav ity, electricity, pain or chronic stress cause specific neural activation to create a gateway of immune cells, particularly pathogenic ones, at specific blood vessels. Moreover, the recently discovered stress-induced gateway reflex uncovered a stress-induced neural link between the brain, gastrointestine, and heart. Thus, the gateway reflex is critical for the homeostasis of various organs, and aberrant activation of neural pathways by the gateway reflex disrupts normal organ homeostasis. The inflammatory reflex is another mechanism for local neuro-immune interactions. It potently exerts a cholinergic anti- inflammatory effect on various disease conditions. In this section, we discuss emerging roles for local neuro-immune interactions, with a special focus on the gateway reflex. sympathetic ganglion (4) and induces the activation of sympathetic nerves (5), which results in norepinephrine (NE) secretion (6) at the L5 dorsal vessels. NE enhances the inflammation amplifier in the L5 dorsal vessels, causing an upregulation of chemokines and recruiting pathogenic CD4+ T cells from the vessels (7).","PeriodicalId":286564,"journal":{"name":"Homeostasis - An Integrated Vision","volume":"69 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115001578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-04-12DOI: 10.5772/INTECHOPEN.76177
J. Lechner, G. Gstraunthaler
Women are not small men. Sex-specific differences do not only affect the classical target organs of sexual differentiation and reproduction, but have been found to involve most, if not all the organs and tissues in the body. One of the consequences of this dimorphism is that diseases manifest in a sexand gender-specific way. Key to maintenance of a healthy state is functioning tissue able to cope with insults. Regulated death of damaged cells and replacement with new cells by proliferation is a prerequisite for maintaining tissue function taking place at different pace in the different organs. The intent of this chapter is to review current evidence for sex-specific differences in tissue homeostasis focusing on the variability of hormone exposure characteristic for the female reproductive life stages.
{"title":"Sex and Sex Hormones in Tissue Homeostasis","authors":"J. Lechner, G. Gstraunthaler","doi":"10.5772/INTECHOPEN.76177","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.76177","url":null,"abstract":"Women are not small men. Sex-specific differences do not only affect the classical target organs of sexual differentiation and reproduction, but have been found to involve most, if not all the organs and tissues in the body. One of the consequences of this dimorphism is that diseases manifest in a sexand gender-specific way. Key to maintenance of a healthy state is functioning tissue able to cope with insults. Regulated death of damaged cells and replacement with new cells by proliferation is a prerequisite for maintaining tissue function taking place at different pace in the different organs. The intent of this chapter is to review current evidence for sex-specific differences in tissue homeostasis focusing on the variability of hormone exposure characteristic for the female reproductive life stages.","PeriodicalId":286564,"journal":{"name":"Homeostasis - An Integrated Vision","volume":"17 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132965348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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