Hematopoietic stem cell transplantation(HSCT)becomes a standard form of cellular therapy for patients with malignant diseases.HSCT is the first-choice of immunotherapy,although HSCT can be associated with many complic...Hematopoietic stem cell transplantation(HSCT)becomes a standard form of cellular therapy for patients with malignant diseases.HSCT is the first-choice of immunotherapy,although HSCT can be associated with many complications such as graft-versus-host disease(GVHD)which is a major cause of morbidity and mortality after allogeneic HSCT.It has been shown that certain gut microbiota could exert protective and/or regenerative immunomodulatory effects by the production of short-chain fatty acids(SCFAs)such as butyrate in the experimental models of GVHD after allogeneic HSCT.Loss of gut commensal bacteria which can produce SCFAs may worsen dysbiosis,increasing the risk of GVHD.Expression of G-protein coupled receptors such as GPR41 seems to be upre-gulated in the presence of commensal bacteria,which might be associated with the biology of regulatory T cells(Tregs).Treg cells are a suppressive subset of CD4 positive T lymphocytes implicated in the prevention of GVHD after allogeneic HSCT.Here,we discuss the current findings of the relationship between the modification of gut microbiota and the GVHD-related immunity,which suggested that tactics with certain probiotics for the beneficial symbiosis in gut-immune axis might lead to the elevation of safety in the allogeneic HSCT.展开更多
Neural regeneration by stem cells transplantation:Tissue regeneration and homeostasis are principally dependent on tissue stem cells which possess abilities of self-renewal and differentiation into multidirectional sp...Neural regeneration by stem cells transplantation:Tissue regeneration and homeostasis are principally dependent on tissue stem cells which possess abilities of self-renewal and differentiation into multidirectional specialized cell types.In general,stem cells are critical for normal tissue renewal as well as repair after tissue injury.For example,mesenchymal stromal cells and endothelial progenitor cells identified in bone marrow展开更多
As an optimal surgical procedure to accurately evaluate lymph node(LN)metastasis during surgery with minimal surgical resection,we have been developing sentinel node(SN)biopsy for early gastric cancer since the 1990s....As an optimal surgical procedure to accurately evaluate lymph node(LN)metastasis during surgery with minimal surgical resection,we have been developing sentinel node(SN)biopsy for early gastric cancer since the 1990s.Twelve institutions from the Japanese Society of Sentinel Node Navigation Surgery(SNNS),including Keio University Hospital,conducted a multicenter prospective trial to validate the SN concept using the dual-tracer method with blue dye and a radioisotope.According to the results,397 patients were included in the final analysis,and the overall accuracy in detecting LN metastasis using SN biopsy was 99%(383 of 387).Based on the validation study,we are targeting cT1N0 with a primary tumor of≤4 cm in diameter as an indication for SN biopsy for gastric cancer.We are currently running a multicenter nonrandomized phaseⅢtrial to assess the safety and efficacy of SN navigation surgery.The Korean group has reported the result of a multicenter randomized phaseⅢtrial.Since meticulous gastric cancer in the remnant stomach was rescued by subsequent gastrectomy,the disease-specific survival was comparable between the two techniques,implying that SN navigation surgery can be an alternative to standard gastrectomy.With the development of SN biopsy procedure and treatment modalities,the application of SN biopsy will be expanded to achieve an individualized minimally invasive surgery.展开更多
Diabetic nephropathy(DN)is a major cause of end-stage renal disease,and therapeutic options for preventing its progression are insufficient.The number of patients with DN has been increasing in Asian countries because...Diabetic nephropathy(DN)is a major cause of end-stage renal disease,and therapeutic options for preventing its progression are insufficient.The number of patients with DN has been increasing in Asian countries because of westernization of dietary lifestyle,which may be associated with the following changes in gut microbiota.Alterations in the gut microbiota composition can lead to an imbalanced gastrointestinal environment that promotes abnormal production of metabolites and/or inflammatory status.Functional microenvironments of the gut could be changed in the different stages of DN.In particular,altered levels of short chain fatty acids,D-amino acids,and reactive oxygen species biosynthesis in the gut have been shown to be relevant to the pathogenesis of the DN.So far,evidence suggests that the gut microbiota may play a key role in determining networks in the development of DN.Interventions directing the gut microbiota deserve further investigation as a new protective therapy in DN.In this review,we discuss the potential roles of the gut microbiota and future perspectives in the protection and/or treatment of kidneys.展开更多
BACKGROUND Despite improvements in surgical procedures and peri-operative patients management,the postoperative complications in esophagogastric junction(EGJ)cancer remain high because of technical aspects.Several stu...BACKGROUND Despite improvements in surgical procedures and peri-operative patients management,the postoperative complications in esophagogastric junction(EGJ)cancer remain high because of technical aspects.Several studies have indicated the negative influence of postoperative infectious complications on long-term survival after gastrointestinal surgery.However,no study has shown the association between postoperative complications and long-term survival of patients with EGJ cancer.AIM To elucidate influence of postoperative complications on the long-term outcomes of patients with EGJ cancer.METHODS A total of 122 patients who underwent surgery for EGJ cancer at the Keio University were included in this study.We examined the association between complications and long-term oncologic outcomes.RESULTS In all patients,the 3-year overall survival(OS)rate was 71.9%,and the recurrencefree survival(RFS)rate was 67.5%.Compared with patients without anastomotic leakage,those with anastomotic leakage had poor median OS(8 mo vs not reached,P=0.028)and median RFS(5 mo vs not reached,P=0.055).Among patients with cervical anastomosis,there were not significant differences between patients with and without anastomotic leakage.However,among patients who underwent intrathoracic anastomosis,patients with anastomotic leakage had significantly worse OS(P=0.002)and RFS(P=0.005).CONCLUSION Anastomotic leakage was significantly associated with long-term oncologic outcomes of patients with EGJ cancer,especially those who underwent intrathoracic anastomosis.Cervical anastomosis with subtotal esophagectomy may be an option for the patients who are at high risk for anastomotic leakage.展开更多
Alzheimer’s disease(AD)is the most common reason for progressive dementia in the elderly.It has been shown that disorders of the mammalian/mechanistic target of rapamycin(mTOR)signaling pathways are related to the AD...Alzheimer’s disease(AD)is the most common reason for progressive dementia in the elderly.It has been shown that disorders of the mammalian/mechanistic target of rapamycin(mTOR)signaling pathways are related to the AD.On the other hand,diabetes mellitus(DM)is a risk factor for the cognitive dysfunction.The pathogenesis of the neuronal impairment caused by diabetic hyperglycemia is intricate,which contains neuro-inflammation and/or neurodegeneration and dementia.Glucagon-like peptide-1(GLP1)is interesting as a possible link between metabolism and brain impairment.Modulation of GLP1 activity can influence amyloid-beta peptide aggregation via the phosphoinositide-3 kinase/AKT/mTOR signaling pathway in AD.The GLP1 receptor agonists have been shown to have favorable actions on the brain such as the improvement of neurological deficit.They might also exert a beneficial effect with refining learning and memory on the cognitive impairment induced by diabetes.Recent experimental and clinical evidence indicates that dipeptidyl-peptidase-4(DPP4)inhibitors,being currently used for DM therapy,may also be effective for AD treatment.The DPP-4 inhibitors have demonstrated neuroprotection and cognitive improvements in animal models.Although further studies for mTOR,GLP1,and DPP4 signaling pathways in humans would be intensively required,they seem to be a promising approach for innovative AD-treatments.We would like to review the characteristics of AD pathogenesis,the key roles of mTOR in AD and the preventive and/or therapeutic suggestions of directing the mTOR signaling pathway.展开更多
Irritable bowel syndrome(IBS)is an important health care concern.Alterations in the microbiota of the gut-brain axis may be linked to the pathophysiology of IBS.Some dietary intake could contribute to produce various ...Irritable bowel syndrome(IBS)is an important health care concern.Alterations in the microbiota of the gut-brain axis may be linked to the pathophysiology of IBS.Some dietary intake could contribute to produce various metabolites including Damino acids by the fermentation by the gut microbiota.D-amino acids are the enantiomeric counterparts of L-amino acids,in general,which could play key roles in cellular physiological processes against various oxidative stresses.Therefore,the presence of D-amino acids has been shown to be linked to the protection of several organs in the body.In particular,the gut microbiota could play significant roles in the stability of emotion via the action of D-amino acids.Here,we would like to shed light on the roles of D-amino acids,which could be used for the treatment of IBS.展开更多
Stemness of cancer cells contains limitless self-renewal proliferation.For the purpose of proliferation,secretome might exert its effects via the paracrine signaling.Specific microRNAs enclosed in the secretome of can...Stemness of cancer cells contains limitless self-renewal proliferation.For the purpose of proliferation,secretome might exert its effects via the paracrine signaling.Specific microRNAs enclosed in the secretome of cancer stem cells could regulate the expression of anti-proliferative APRO family proteins.The biological functions of APRO family proteins seems to be quite intricate,however,which might be a key modulator of microRNAs,then could regulate the proliferation of cancer cells.In addition to affecting proliferation/differentiation during cellular development,APRO family proteins might also play an imperious role on keeping homeostasis in healthy stem cells under a physiological condition.Therefore,relationship between the microRNAs and the APRO family proteins has attracted much attention in the field of cancer research and regenerative medicine.Here,we have described the molecular mechanism behind this interplay that have a potential role in the future promising tools with targeting APRO family proteins for the medical applications.展开更多
Coal-fired Integrated Gasification Combined Cycle(IGCC)and Integrated coal Gasification Fuel-cell Combined cycle(IGFC)are being developed as high-efficiency electric power generation technology.However,the highest the...Coal-fired Integrated Gasification Combined Cycle(IGCC)and Integrated coal Gasification Fuel-cell Combined cycle(IGFC)are being developed as high-efficiency electric power generation technology.However,the highest theoretical gross thermal efficiency of the conventional IGCC/IGFC is still below 52%.In order to obtain higher power generation efficiency,an advanced IGCC(A-IGCC)or advanced IGFC(A-IGFC)system making use of the exergy recuperation concept by recycling waste heat from gas turbine or fuel cells for steam gasification of coal and biomass was proposed in our laboratory.Corresponding to this system,a novel high-density triple-bed combined circulating fluidized bed(TBCFB)gasifier,composed of a downer pyrolyzer,a bubbling fluidized bed char gasifier,and a riser combustor,was proposed to replace traditional gasifiers such as the entrained flow bed gasifier.The new system is expected to more effectively utilize the waste heat from gas turbines or fuel cells and the heat produced by the combustion of the unreacted char in the riser combustor for pyrolysis and gasification of coal and biomass.In this short review,the advantages and future challenges in the development of high-density TBCFB gasifier are presented and discussed.展开更多
文摘Hematopoietic stem cell transplantation(HSCT)becomes a standard form of cellular therapy for patients with malignant diseases.HSCT is the first-choice of immunotherapy,although HSCT can be associated with many complications such as graft-versus-host disease(GVHD)which is a major cause of morbidity and mortality after allogeneic HSCT.It has been shown that certain gut microbiota could exert protective and/or regenerative immunomodulatory effects by the production of short-chain fatty acids(SCFAs)such as butyrate in the experimental models of GVHD after allogeneic HSCT.Loss of gut commensal bacteria which can produce SCFAs may worsen dysbiosis,increasing the risk of GVHD.Expression of G-protein coupled receptors such as GPR41 seems to be upre-gulated in the presence of commensal bacteria,which might be associated with the biology of regulatory T cells(Tregs).Treg cells are a suppressive subset of CD4 positive T lymphocytes implicated in the prevention of GVHD after allogeneic HSCT.Here,we discuss the current findings of the relationship between the modification of gut microbiota and the GVHD-related immunity,which suggested that tactics with certain probiotics for the beneficial symbiosis in gut-immune axis might lead to the elevation of safety in the allogeneic HSCT.
文摘Neural regeneration by stem cells transplantation:Tissue regeneration and homeostasis are principally dependent on tissue stem cells which possess abilities of self-renewal and differentiation into multidirectional specialized cell types.In general,stem cells are critical for normal tissue renewal as well as repair after tissue injury.For example,mesenchymal stromal cells and endothelial progenitor cells identified in bone marrow
文摘As an optimal surgical procedure to accurately evaluate lymph node(LN)metastasis during surgery with minimal surgical resection,we have been developing sentinel node(SN)biopsy for early gastric cancer since the 1990s.Twelve institutions from the Japanese Society of Sentinel Node Navigation Surgery(SNNS),including Keio University Hospital,conducted a multicenter prospective trial to validate the SN concept using the dual-tracer method with blue dye and a radioisotope.According to the results,397 patients were included in the final analysis,and the overall accuracy in detecting LN metastasis using SN biopsy was 99%(383 of 387).Based on the validation study,we are targeting cT1N0 with a primary tumor of≤4 cm in diameter as an indication for SN biopsy for gastric cancer.We are currently running a multicenter nonrandomized phaseⅢtrial to assess the safety and efficacy of SN navigation surgery.The Korean group has reported the result of a multicenter randomized phaseⅢtrial.Since meticulous gastric cancer in the remnant stomach was rescued by subsequent gastrectomy,the disease-specific survival was comparable between the two techniques,implying that SN navigation surgery can be an alternative to standard gastrectomy.With the development of SN biopsy procedure and treatment modalities,the application of SN biopsy will be expanded to achieve an individualized minimally invasive surgery.
文摘Diabetic nephropathy(DN)is a major cause of end-stage renal disease,and therapeutic options for preventing its progression are insufficient.The number of patients with DN has been increasing in Asian countries because of westernization of dietary lifestyle,which may be associated with the following changes in gut microbiota.Alterations in the gut microbiota composition can lead to an imbalanced gastrointestinal environment that promotes abnormal production of metabolites and/or inflammatory status.Functional microenvironments of the gut could be changed in the different stages of DN.In particular,altered levels of short chain fatty acids,D-amino acids,and reactive oxygen species biosynthesis in the gut have been shown to be relevant to the pathogenesis of the DN.So far,evidence suggests that the gut microbiota may play a key role in determining networks in the development of DN.Interventions directing the gut microbiota deserve further investigation as a new protective therapy in DN.In this review,we discuss the potential roles of the gut microbiota and future perspectives in the protection and/or treatment of kidneys.
文摘BACKGROUND Despite improvements in surgical procedures and peri-operative patients management,the postoperative complications in esophagogastric junction(EGJ)cancer remain high because of technical aspects.Several studies have indicated the negative influence of postoperative infectious complications on long-term survival after gastrointestinal surgery.However,no study has shown the association between postoperative complications and long-term survival of patients with EGJ cancer.AIM To elucidate influence of postoperative complications on the long-term outcomes of patients with EGJ cancer.METHODS A total of 122 patients who underwent surgery for EGJ cancer at the Keio University were included in this study.We examined the association between complications and long-term oncologic outcomes.RESULTS In all patients,the 3-year overall survival(OS)rate was 71.9%,and the recurrencefree survival(RFS)rate was 67.5%.Compared with patients without anastomotic leakage,those with anastomotic leakage had poor median OS(8 mo vs not reached,P=0.028)and median RFS(5 mo vs not reached,P=0.055).Among patients with cervical anastomosis,there were not significant differences between patients with and without anastomotic leakage.However,among patients who underwent intrathoracic anastomosis,patients with anastomotic leakage had significantly worse OS(P=0.002)and RFS(P=0.005).CONCLUSION Anastomotic leakage was significantly associated with long-term oncologic outcomes of patients with EGJ cancer,especially those who underwent intrathoracic anastomosis.Cervical anastomosis with subtotal esophagectomy may be an option for the patients who are at high risk for anastomotic leakage.
文摘Alzheimer’s disease(AD)is the most common reason for progressive dementia in the elderly.It has been shown that disorders of the mammalian/mechanistic target of rapamycin(mTOR)signaling pathways are related to the AD.On the other hand,diabetes mellitus(DM)is a risk factor for the cognitive dysfunction.The pathogenesis of the neuronal impairment caused by diabetic hyperglycemia is intricate,which contains neuro-inflammation and/or neurodegeneration and dementia.Glucagon-like peptide-1(GLP1)is interesting as a possible link between metabolism and brain impairment.Modulation of GLP1 activity can influence amyloid-beta peptide aggregation via the phosphoinositide-3 kinase/AKT/mTOR signaling pathway in AD.The GLP1 receptor agonists have been shown to have favorable actions on the brain such as the improvement of neurological deficit.They might also exert a beneficial effect with refining learning and memory on the cognitive impairment induced by diabetes.Recent experimental and clinical evidence indicates that dipeptidyl-peptidase-4(DPP4)inhibitors,being currently used for DM therapy,may also be effective for AD treatment.The DPP-4 inhibitors have demonstrated neuroprotection and cognitive improvements in animal models.Although further studies for mTOR,GLP1,and DPP4 signaling pathways in humans would be intensively required,they seem to be a promising approach for innovative AD-treatments.We would like to review the characteristics of AD pathogenesis,the key roles of mTOR in AD and the preventive and/or therapeutic suggestions of directing the mTOR signaling pathway.
文摘Irritable bowel syndrome(IBS)is an important health care concern.Alterations in the microbiota of the gut-brain axis may be linked to the pathophysiology of IBS.Some dietary intake could contribute to produce various metabolites including Damino acids by the fermentation by the gut microbiota.D-amino acids are the enantiomeric counterparts of L-amino acids,in general,which could play key roles in cellular physiological processes against various oxidative stresses.Therefore,the presence of D-amino acids has been shown to be linked to the protection of several organs in the body.In particular,the gut microbiota could play significant roles in the stability of emotion via the action of D-amino acids.Here,we would like to shed light on the roles of D-amino acids,which could be used for the treatment of IBS.
文摘Stemness of cancer cells contains limitless self-renewal proliferation.For the purpose of proliferation,secretome might exert its effects via the paracrine signaling.Specific microRNAs enclosed in the secretome of cancer stem cells could regulate the expression of anti-proliferative APRO family proteins.The biological functions of APRO family proteins seems to be quite intricate,however,which might be a key modulator of microRNAs,then could regulate the proliferation of cancer cells.In addition to affecting proliferation/differentiation during cellular development,APRO family proteins might also play an imperious role on keeping homeostasis in healthy stem cells under a physiological condition.Therefore,relationship between the microRNAs and the APRO family proteins has attracted much attention in the field of cancer research and regenerative medicine.Here,we have described the molecular mechanism behind this interplay that have a potential role in the future promising tools with targeting APRO family proteins for the medical applications.
基金supported by the New Energy and Industrial Technology Development Organization(NEDO)
文摘Coal-fired Integrated Gasification Combined Cycle(IGCC)and Integrated coal Gasification Fuel-cell Combined cycle(IGFC)are being developed as high-efficiency electric power generation technology.However,the highest theoretical gross thermal efficiency of the conventional IGCC/IGFC is still below 52%.In order to obtain higher power generation efficiency,an advanced IGCC(A-IGCC)or advanced IGFC(A-IGFC)system making use of the exergy recuperation concept by recycling waste heat from gas turbine or fuel cells for steam gasification of coal and biomass was proposed in our laboratory.Corresponding to this system,a novel high-density triple-bed combined circulating fluidized bed(TBCFB)gasifier,composed of a downer pyrolyzer,a bubbling fluidized bed char gasifier,and a riser combustor,was proposed to replace traditional gasifiers such as the entrained flow bed gasifier.The new system is expected to more effectively utilize the waste heat from gas turbines or fuel cells and the heat produced by the combustion of the unreacted char in the riser combustor for pyrolysis and gasification of coal and biomass.In this short review,the advantages and future challenges in the development of high-density TBCFB gasifier are presented and discussed.
