INTRODUCTIONThe transforming growth factor-β （TGF-β） superfamily com- prises TGF-βs, Activin, bone morphogenetic proteins （BMPs） and other related proteins. TGF-β superfamily members act through a heteromeric ...INTRODUCTIONThe transforming growth factor-β （TGF-β） superfamily com- prises TGF-βs, Activin, bone morphogenetic proteins （BMPs） and other related proteins. TGF-β superfamily members act through a heteromeric receptor complex,, comprised of type I and type II receptors at the cell surface that transduce intracellular signals via Smad complex or mitogen-activated protein kinase （MAPK） cascade.展开更多
AIM: To evaluate safety and feasibility of autologous bone marrow-enriched CD34+ hematopoietic stem cell Tx through the hepatic artery in patients with decompensated cirrhosis.METHODS: Four patients with decompensated...AIM: To evaluate safety and feasibility of autologous bone marrow-enriched CD34+ hematopoietic stem cell Tx through the hepatic artery in patients with decompensated cirrhosis.METHODS: Four patients with decompensated cirrhosis were included. Approximately 200 mL of the bone marrow of the patients was aspirated, and CD34+ stem cells were selected. Between 3 to 10 million CD34+ cells were isolated. The cells were slowly infused through the hepatic artery of the patients.RESULTS: Patient 1 showed marginal improvement in serum albumin and no significant changes in other test results. In patient 2 prothrombin time was decreased; however, her total bilirubin, serum creatinine, and Model of End-Stage Liver Disease (MELD) score worsened at the end of follow up. In patient 3 there was improvement in serum albumin, porthrombin time (PT), and MELD score. Patient 4 developed radiocontrast nephropathy after the procedure, and progressed to type 1 hepatorenal syndrome and died of liver failure a few days later. Because of the major side effects seen in the last patient, the trial was prematurely stopped.CONCLUSION: Infusion of CD34+ stem cells through the hepatic artery is not safe in decompensated cirrhosis. Radiocontrast nephropathy and hepatorenal syndrome could be major side effects. However, this study doesnot preclude infusion of CD34+ stem cells through other routes.展开更多
AIM： To estimate the prevalence and identify the risk factors for metabolic bone disease in patients with cirrhosis. METHODS： The study was performed on 72 Indian patients with cirrhosis （63 male, 9 female; aged 〈...AIM： To estimate the prevalence and identify the risk factors for metabolic bone disease in patients with cirrhosis. METHODS： The study was performed on 72 Indian patients with cirrhosis （63 male, 9 female; aged 〈 50 years）. Etiology of cirrhosis was alcoholism （n = 37）, hepatitis B （n = 25） and hepatitis C （n = 10）. Twenty-three patients belonged to Child class A, while 39 were in class B and 10 in class C. Secondary causes for metabolic bone disease and osteoporosis were ruled out. Sunlight exposure, physical activity and dietary constituents were calculated. Complete metabolic profiles were derived, and bone mineral density （BMD） was measured using dual energy X ray absorptiometry. Low BMD was defined as a Z score below -2. RESULTS： Low BMD was found in 68% of patients. Lumbar spine was the most frequently and severely affected site. Risk factors for low BMD included low physical activity, decreased sunlight exposure, and low lean body mass. Calcium intake was adequate, with unfavorable calcium： protein ratio and calcium： phosphorus ratio. Vitamin D deficiency was highly prevalent （92%）. There was a high incidence of hypogonadism （41%）. Serum estradiol level was elevated significantly in patients with normal BMD. Insulin-like growth factor （IGF） 1 and IGF binding protein 3 levels were below the age-related normal range in both groups. IGF-1 was significantly lower in patients with low BMD. Serum osteocalcin level was low （68%） and urinary deoxypyridinoline to creatinine ratio was high （79%）, which demonstrated low bone formation with high resorption. CONCLUSION： Patients with cirrhosis have low BMD. Contributory factors are reduced physical activity, low lean body mass, vitamin D deficiency and hypogonadism and low IGF-1 level.展开更多
Alcoholic fatty liver disease (AFLD), a potentially pathologic condition, can progress to steatohepatitis, fibrosis, and cirrhosis, leading to an increased probability of hepatic failure and death. Alcohol induces fat...Alcoholic fatty liver disease (AFLD), a potentially pathologic condition, can progress to steatohepatitis, fibrosis, and cirrhosis, leading to an increased probability of hepatic failure and death. Alcohol induces fatty liver by increasing the ratio of reduced form of nicotinamide adenine dinucleotide to oxidized form of nicotinamide adenine dinucleotide in hepatocytes; increasing hepatic sterol regulatory element-binding protein (SREBP)-1, plasminogen activator inhibitor (PAI)-1, and early growth response-1 activity; and decreasing hepatic peroxisome proliferator-activated receptor-α activity. Alcohol activates the innate immune system and induces an imbalance of the immune response, which is followed by activated Kupffer cell-derived tumor necrosis factor (TNF)-α overproduction, which is in turn responsible for the changes in the hepatic SREBP-1 and PAI-1 activity. Alcohol abuse promotes the migration of bone marrow-derived cells (BMDCs) to the liver and then reprograms TNF-α expression from BMDCs. Chronic alcohol intake triggers the sympathetic hyperactivity-activated hepatic stellate cell (HSC) feedback loop that in turn activates the HSCs, resulting in HSC-derived TNF-α overproduction. Carvedilol may block this feedback loop by suppressing sympathetic activity, which attenuates the progression of AFLD. Clinical studies evaluating combination therapy of carvedilol with a TNF-α inhibitor to treat patients with AFLD are warranted to prevent the development of alcoholic liver disease.展开更多
Background:Despite a growing population of patients starting hemodialysis in China,little is known about markers of mineral bone disease(MBD)and their management.We present data on prevalence and correlates of hypocal...Background:Despite a growing population of patients starting hemodialysis in China,little is known about markers of mineral bone disease(MBD)and their management.We present data on prevalence and correlates of hypocalcemia,hyperphosphatemia,and secondary hyperparathyroidism from the China Dialysis Outcomes and Practice Patterns Study(DOPPS),with evaluation of whether these laboratory markers triggered changes in management.Methods:We compared the frequency of measurement and prevalence of poor control of MBD markers in China DOPPS with other DOPPS regions.We also used generalized estimating equations to assess correlates of MBD markers,and separate models to assess predictors of vitamin D and phosphate binder prescriptions in the China DOPPS.Results:Severe hyperphosphatemia(>7 mg/dL)and secondary hyperparathyroidism(>600 pg/mL)were common(27%and 21%prevalence,respectively);both were measured infrequently(14.9%and 3.2%of patients received monthly measurements in China).Frequency of dialysis sessions was positively associated with hyperphosphatemia;presence of residual kidney function was negatively associated with both hyperphosphatemia and secondary hyperparathyroidism.Laboratory measures indicating poor control of MBD were not associated with subsequent prescription of active vitamin D or phosphate binder.Conclusions:There are substantial opportunities for improvement and standardization of MBD management in China.Development of country-specific guidelines may yield realistic targets and standardization of medication use accounting for availability and cost.展开更多
Bone defects repair and regeneration by various causes such as tumor resection, trauma, degeneration, etc. havealways been a key issue in the clinics. As one of the few organs that can regenerate after adulthood, bone...Bone defects repair and regeneration by various causes such as tumor resection, trauma, degeneration, etc. havealways been a key issue in the clinics. As one of the few organs that can regenerate after adulthood, bone itselfhas a strong regenerative ability. In recent decades, bone tissue engineering technology provides various types offunctional scaffold materials and seed cells for bone regeneration and repair, which significantly accelerates thespeed and quality of bone regeneration, and many clinical problems are gradually solved. However, the bonemetabolism mechanism is complicated, the research duration is long and difficult, which significantly restrictsthe progress of bone regeneration and repair research. Organoids as a new concept, which is built in vitro withthe help of tissue engineering technology based on biological theory, can simulate the complex biologicalfunctions of organs in vivo. Once proposed, it shows broad application prospects in the research of organdevelopment, drug screening, mechanism study, and so on. As a complex and special organ, bone organoidconstruction itself is quite challenging. This review will introduce the characteristics of bone microenvironment,the concept of organoids, focus on the research progress of bone organoids, and propose the strategies for boneorganoid construction, study direction, and application prospects.展开更多
基金supported by grants by NIH grant AR-044741(Y-PL) and R01DE023813 (Y-PL)
文摘INTRODUCTIONThe transforming growth factor-β （TGF-β） superfamily com- prises TGF-βs, Activin, bone morphogenetic proteins （BMPs） and other related proteins. TGF-β superfamily members act through a heteromeric receptor complex,, comprised of type I and type II receptors at the cell surface that transduce intracellular signals via Smad complex or mitogen-activated protein kinase （MAPK） cascade.
文摘AIM: To evaluate safety and feasibility of autologous bone marrow-enriched CD34+ hematopoietic stem cell Tx through the hepatic artery in patients with decompensated cirrhosis.METHODS: Four patients with decompensated cirrhosis were included. Approximately 200 mL of the bone marrow of the patients was aspirated, and CD34+ stem cells were selected. Between 3 to 10 million CD34+ cells were isolated. The cells were slowly infused through the hepatic artery of the patients.RESULTS: Patient 1 showed marginal improvement in serum albumin and no significant changes in other test results. In patient 2 prothrombin time was decreased; however, her total bilirubin, serum creatinine, and Model of End-Stage Liver Disease (MELD) score worsened at the end of follow up. In patient 3 there was improvement in serum albumin, porthrombin time (PT), and MELD score. Patient 4 developed radiocontrast nephropathy after the procedure, and progressed to type 1 hepatorenal syndrome and died of liver failure a few days later. Because of the major side effects seen in the last patient, the trial was prematurely stopped.CONCLUSION: Infusion of CD34+ stem cells through the hepatic artery is not safe in decompensated cirrhosis. Radiocontrast nephropathy and hepatorenal syndrome could be major side effects. However, this study doesnot preclude infusion of CD34+ stem cells through other routes.
基金Supported by Corpus generated by Department of Endocrinology, KEM Hospital, Mumbai, India
文摘AIM： To estimate the prevalence and identify the risk factors for metabolic bone disease in patients with cirrhosis. METHODS： The study was performed on 72 Indian patients with cirrhosis （63 male, 9 female; aged 〈 50 years）. Etiology of cirrhosis was alcoholism （n = 37）, hepatitis B （n = 25） and hepatitis C （n = 10）. Twenty-three patients belonged to Child class A, while 39 were in class B and 10 in class C. Secondary causes for metabolic bone disease and osteoporosis were ruled out. Sunlight exposure, physical activity and dietary constituents were calculated. Complete metabolic profiles were derived, and bone mineral density （BMD） was measured using dual energy X ray absorptiometry. Low BMD was defined as a Z score below -2. RESULTS： Low BMD was found in 68% of patients. Lumbar spine was the most frequently and severely affected site. Risk factors for low BMD included low physical activity, decreased sunlight exposure, and low lean body mass. Calcium intake was adequate, with unfavorable calcium： protein ratio and calcium： phosphorus ratio. Vitamin D deficiency was highly prevalent （92%）. There was a high incidence of hypogonadism （41%）. Serum estradiol level was elevated significantly in patients with normal BMD. Insulin-like growth factor （IGF） 1 and IGF binding protein 3 levels were below the age-related normal range in both groups. IGF-1 was significantly lower in patients with low BMD. Serum osteocalcin level was low （68%） and urinary deoxypyridinoline to creatinine ratio was high （79%）, which demonstrated low bone formation with high resorption. CONCLUSION： Patients with cirrhosis have low BMD. Contributory factors are reduced physical activity, low lean body mass, vitamin D deficiency and hypogonadism and low IGF-1 level.
文摘Alcoholic fatty liver disease (AFLD), a potentially pathologic condition, can progress to steatohepatitis, fibrosis, and cirrhosis, leading to an increased probability of hepatic failure and death. Alcohol induces fatty liver by increasing the ratio of reduced form of nicotinamide adenine dinucleotide to oxidized form of nicotinamide adenine dinucleotide in hepatocytes; increasing hepatic sterol regulatory element-binding protein (SREBP)-1, plasminogen activator inhibitor (PAI)-1, and early growth response-1 activity; and decreasing hepatic peroxisome proliferator-activated receptor-α activity. Alcohol activates the innate immune system and induces an imbalance of the immune response, which is followed by activated Kupffer cell-derived tumor necrosis factor (TNF)-α overproduction, which is in turn responsible for the changes in the hepatic SREBP-1 and PAI-1 activity. Alcohol abuse promotes the migration of bone marrow-derived cells (BMDCs) to the liver and then reprograms TNF-α expression from BMDCs. Chronic alcohol intake triggers the sympathetic hyperactivity-activated hepatic stellate cell (HSC) feedback loop that in turn activates the HSCs, resulting in HSC-derived TNF-α overproduction. Carvedilol may block this feedback loop by suppressing sympathetic activity, which attenuates the progression of AFLD. Clinical studies evaluating combination therapy of carvedilol with a TNF-α inhibitor to treat patients with AFLD are warranted to prevent the development of alcoholic liver disease.
基金This work was supported by grants from the Global support for the ongoing DOPPS Programs without restriction on publications by a variety of funders(For details see https://www.dopps.org/AboutUs/Support.aspx)Dr.Shuchi Anand is supported by U.S.National Institute of Diabetes,and Digestive and Kidney Diseases(No.NIDDK K-235K23DK101826-03)Dr.Jun Wang is supported by the National Natural Science Foundation of China(No.81470972).
文摘Background:Despite a growing population of patients starting hemodialysis in China,little is known about markers of mineral bone disease(MBD)and their management.We present data on prevalence and correlates of hypocalcemia,hyperphosphatemia,and secondary hyperparathyroidism from the China Dialysis Outcomes and Practice Patterns Study(DOPPS),with evaluation of whether these laboratory markers triggered changes in management.Methods:We compared the frequency of measurement and prevalence of poor control of MBD markers in China DOPPS with other DOPPS regions.We also used generalized estimating equations to assess correlates of MBD markers,and separate models to assess predictors of vitamin D and phosphate binder prescriptions in the China DOPPS.Results:Severe hyperphosphatemia(>7 mg/dL)and secondary hyperparathyroidism(>600 pg/mL)were common(27%and 21%prevalence,respectively);both were measured infrequently(14.9%and 3.2%of patients received monthly measurements in China).Frequency of dialysis sessions was positively associated with hyperphosphatemia;presence of residual kidney function was negatively associated with both hyperphosphatemia and secondary hyperparathyroidism.Laboratory measures indicating poor control of MBD were not associated with subsequent prescription of active vitamin D or phosphate binder.Conclusions:There are substantial opportunities for improvement and standardization of MBD management in China.Development of country-specific guidelines may yield realistic targets and standardization of medication use accounting for availability and cost.
基金the National Key Research and Development Plan(2018YFC2001500)National Natural Science Foundation of China(82172098,81972254,81871099,32101084)Shanghai Rising-Star Program(21QA1412000).
文摘Bone defects repair and regeneration by various causes such as tumor resection, trauma, degeneration, etc. havealways been a key issue in the clinics. As one of the few organs that can regenerate after adulthood, bone itselfhas a strong regenerative ability. In recent decades, bone tissue engineering technology provides various types offunctional scaffold materials and seed cells for bone regeneration and repair, which significantly accelerates thespeed and quality of bone regeneration, and many clinical problems are gradually solved. However, the bonemetabolism mechanism is complicated, the research duration is long and difficult, which significantly restrictsthe progress of bone regeneration and repair research. Organoids as a new concept, which is built in vitro withthe help of tissue engineering technology based on biological theory, can simulate the complex biologicalfunctions of organs in vivo. Once proposed, it shows broad application prospects in the research of organdevelopment, drug screening, mechanism study, and so on. As a complex and special organ, bone organoidconstruction itself is quite challenging. This review will introduce the characteristics of bone microenvironment,the concept of organoids, focus on the research progress of bone organoids, and propose the strategies for boneorganoid construction, study direction, and application prospects.
