Biodegradable stents have tremendous theoretical potential as an alternative to bare metal stents and drug-eluting stents for the treatment of obstructive coronary artery disease.Any bioresorbable or biodegradable sca...Biodegradable stents have tremendous theoretical potential as an alternative to bare metal stents and drug-eluting stents for the treatment of obstructive coronary artery disease.Any bioresorbable or biodegradable scaffold material needs to possess optimal mechanical properties and uniform degradation behavior that avoids local and systemic toxicity.Recently,molybdenum(Mo)has been investigated as a potential novel biodegradable material for this purpose.With its proven moderate degradation rate and excellent mechanical properties,Mo may represent an ideal source material for clinical cardiac and vascular applications.The present study was performed to evaluate the mechanical performance of metallic Mo in vitro and the biodegradation properties in vivo.The results demonstrated favorable mechanical behavior and a uniform degradation profile as desired for a new generation ultra-thin degradable endovascular stent material.Moreover,Mo implants in mouse arteries avoided the typical cellular response that contributes to restenosis.There was minimal neointimal hyperplasia over 6 months,an absence of excessive smooth muscle cell(SMC)proliferation or inflammation near the implant,and avoidance of significant harm to regenerating endothelial cells(EC).Qualitative inspection of kidney sections showed a potentially pathological remodeling of kidney Bowman’s capsule and glomeruli,indicative of impaired filtering function and development of kidney disease,although quantifications of these morphological changes were not statistically significant.Together,the results suggest that the products of Mo corrosion may exert beneficial or inert effects on the activities of inflammatory and arterial cells,while exerting potentially toxic effects in the kidneys that warrant further investigation.展开更多
After more than one hundred years of documented trials,immunotherapy has become a standard of care in the treatment of human cancer.Much of the knowledge that led to recent breakthroughs seems quite logical from today...After more than one hundred years of documented trials,immunotherapy has become a standard of care in the treatment of human cancer.Much of the knowledge that led to recent breakthroughs seems quite logical from today’s point of view.However,what we now cite as facts were originally considered paradoxes,meaning something contrary to expectations or perceived opinion at the time.In order to make gains in the field of immunotherapy,one had to be willing to confront ideas and concepts that seemed to contradict one another,and reconcile how each could be true.This is what led to new knowledge and advances.Here,we highlight some of these paradoxes and the milestone discoveries that followed,each one critical for our understanding of immune checkpoint pathways.By outlining some of the steps that we took and the challenges that we overcame,we hope to inspire and encourage future generations of researchers to confront the paradoxes that still permeate the field.展开更多
Therapy resistance is a significant challenge for prostate cancer treatment in clinic. Although targeted therapies such as androgen deprivation and androgen receptor (AR) inhibition are effective initially, tumor cell...Therapy resistance is a significant challenge for prostate cancer treatment in clinic. Although targeted therapies such as androgen deprivation and androgen receptor (AR) inhibition are effective initially, tumor cells eventually evade these strategies through multiple mechanisms. Lineage reprogramming in response to hormone therapy represents a key mechanism that is increasingly observed. The studies in this area have revealed specific combinations of alterations present in adenocarcinomas that provide cells with the ability to transdifferentiate and perpetuate AR-independent tumor growth after androgen-based therapies. Interestingly, several master regulators have been identified that drive plasticity, some of which also play key roles during development and differentiation of the cell lineages in the normal prostate. Thus, further study of each AR-independent tumor type and understanding underlying mechanisms are warranted to develop combinational therapies that combat lineage plasticity in prostate cancer.展开更多
Human lifespan continues to extend as an unprecedented number of people reach their seventh and eighth decades of life,unveiling chronic conditions that affect the older adult.Age-related skin conditions include senil...Human lifespan continues to extend as an unprecedented number of people reach their seventh and eighth decades of life,unveiling chronic conditions that affect the older adult.Age-related skin conditions include senile purpura,seborrheic keratoses,pemphigus vulgaris,bullous pemphigoid,diabetic foot wounds and skin cancer.Current methods of drug testing prior to clinical trials require the use of pre-clinical animal models,which are often unable to adequately replicate human skin response.Therefore,a reliable model for aged human skin is needed.The current challenges in developing an aged human skin model include the intrinsic variability in skin architecture from person to person.An ideal skin model would incorporate innate functionality such as sensation,vascularization and regeneration.The advent of 3D bioprinting allows us to create human skin equivalent for use as clinical-grade surgical graft,for drug testing and other needs.In this review,we describe the process of human skin aging and outline the steps to create an aged skin model with 3D bioprinting using skin cells(i.e.keratinocytes,fibroblasts and melanocytes).We also provide an overview of current bioprinted skin models,associated limitations and direction for future research.展开更多
基金U.S.National Institute of Health-National Heart,Lung,and Blood Institute grants R15HL147299 and R01HL144739 are acknowledged for funding this work.
文摘Biodegradable stents have tremendous theoretical potential as an alternative to bare metal stents and drug-eluting stents for the treatment of obstructive coronary artery disease.Any bioresorbable or biodegradable scaffold material needs to possess optimal mechanical properties and uniform degradation behavior that avoids local and systemic toxicity.Recently,molybdenum(Mo)has been investigated as a potential novel biodegradable material for this purpose.With its proven moderate degradation rate and excellent mechanical properties,Mo may represent an ideal source material for clinical cardiac and vascular applications.The present study was performed to evaluate the mechanical performance of metallic Mo in vitro and the biodegradation properties in vivo.The results demonstrated favorable mechanical behavior and a uniform degradation profile as desired for a new generation ultra-thin degradable endovascular stent material.Moreover,Mo implants in mouse arteries avoided the typical cellular response that contributes to restenosis.There was minimal neointimal hyperplasia over 6 months,an absence of excessive smooth muscle cell(SMC)proliferation or inflammation near the implant,and avoidance of significant harm to regenerating endothelial cells(EC).Qualitative inspection of kidney sections showed a potentially pathological remodeling of kidney Bowman’s capsule and glomeruli,indicative of impaired filtering function and development of kidney disease,although quantifications of these morphological changes were not statistically significant.Together,the results suggest that the products of Mo corrosion may exert beneficial or inert effects on the activities of inflammatory and arterial cells,while exerting potentially toxic effects in the kidneys that warrant further investigation.
基金Acknowledgements and conflicts of interestThe authors declare no conflicts of interest.
文摘After more than one hundred years of documented trials,immunotherapy has become a standard of care in the treatment of human cancer.Much of the knowledge that led to recent breakthroughs seems quite logical from today’s point of view.However,what we now cite as facts were originally considered paradoxes,meaning something contrary to expectations or perceived opinion at the time.In order to make gains in the field of immunotherapy,one had to be willing to confront ideas and concepts that seemed to contradict one another,and reconcile how each could be true.This is what led to new knowledge and advances.Here,we highlight some of these paradoxes and the milestone discoveries that followed,each one critical for our understanding of immune checkpoint pathways.By outlining some of the steps that we took and the challenges that we overcame,we hope to inspire and encourage future generations of researchers to confront the paradoxes that still permeate the field.
文摘Therapy resistance is a significant challenge for prostate cancer treatment in clinic. Although targeted therapies such as androgen deprivation and androgen receptor (AR) inhibition are effective initially, tumor cells eventually evade these strategies through multiple mechanisms. Lineage reprogramming in response to hormone therapy represents a key mechanism that is increasingly observed. The studies in this area have revealed specific combinations of alterations present in adenocarcinomas that provide cells with the ability to transdifferentiate and perpetuate AR-independent tumor growth after androgen-based therapies. Interestingly, several master regulators have been identified that drive plasticity, some of which also play key roles during development and differentiation of the cell lineages in the normal prostate. Thus, further study of each AR-independent tumor type and understanding underlying mechanisms are warranted to develop combinational therapies that combat lineage plasticity in prostate cancer.
文摘Human lifespan continues to extend as an unprecedented number of people reach their seventh and eighth decades of life,unveiling chronic conditions that affect the older adult.Age-related skin conditions include senile purpura,seborrheic keratoses,pemphigus vulgaris,bullous pemphigoid,diabetic foot wounds and skin cancer.Current methods of drug testing prior to clinical trials require the use of pre-clinical animal models,which are often unable to adequately replicate human skin response.Therefore,a reliable model for aged human skin is needed.The current challenges in developing an aged human skin model include the intrinsic variability in skin architecture from person to person.An ideal skin model would incorporate innate functionality such as sensation,vascularization and regeneration.The advent of 3D bioprinting allows us to create human skin equivalent for use as clinical-grade surgical graft,for drug testing and other needs.In this review,we describe the process of human skin aging and outline the steps to create an aged skin model with 3D bioprinting using skin cells(i.e.keratinocytes,fibroblasts and melanocytes).We also provide an overview of current bioprinted skin models,associated limitations and direction for future research.
