BACKGROUND Special AT-rich sequence binding protein 2(SATB2)-associated syndrome(SAS;OMIM 612313)is an autosomal dominant disorder.Alterations in the SATB2 gene have been identified as causative.CASE SUMMARY We report...BACKGROUND Special AT-rich sequence binding protein 2(SATB2)-associated syndrome(SAS;OMIM 612313)is an autosomal dominant disorder.Alterations in the SATB2 gene have been identified as causative.CASE SUMMARY We report a case of a 13-year-old Chinese boy with lifelong global developmental delay,speech and language delay,and intellectual disabilities.He had short stature and irregular dentition,but no other abnormal clinical findings.A de novo heterozygous nonsense point mutation was detected by genetic analysis in exon 6 of SATB2,c.687C>A(p.Y229X)(NCBI reference sequence:NM_001172509.2),and neither of his parents had the mutation.This mutation is the first reported and was evaluated as pathogenic according to the guidelines from the American College of Medical Genetics and Genomics.SAS was diagnosed,and special education performed.Our report of a SAS case in China caused by a SATB2 mutation expanded the genotype options for the disease.The heterogeneous manifestations can be induced by complicated pathogenic involvements and functions of SATB2 from reviewed literatures:(1)SATB2 haploinsufficiency;(2)the interference of truncated SATB2 protein to wild-type SATB2;and(3)different numerous genes regulated by SATB2 in brain and skeletal development in different developmental stages.CONCLUSION Global developmental delays are usually the initial presentations,and the diagnosis was challenging before other presentations occurred.Regular follow-up and genetic analysis can help to diagnose SAS early.Verification for genes affected by SATB2 mutations for heterogeneous manifestations may help to clarify the possible pathogenesis of SAS in the future.展开更多
OBJECTIVE:To study on effects of Lichong decoction on expression of apoptosis-controlling genes,Bcl-2 and Bcl-2-associated X protein(Bax) mRNAs in hysteromyoma tissue of the hysteromyoma model rat.METHODS:Fifty Wistar...OBJECTIVE:To study on effects of Lichong decoction on expression of apoptosis-controlling genes,Bcl-2 and Bcl-2-associated X protein(Bax) mRNAs in hysteromyoma tissue of the hysteromyoma model rat.METHODS:Fifty Wistar female rats were randomly divided into a normal group,a model group,a Lichong decoction group,a Guizifuling capsule group and a Mifepristone group.The hysteromyoma rat model was established by intraperitoneal injection of exogenous estrin and progestogens.Pathological examination of uterine tissue,uterine coefficient and uterine transverse diameter were made under optic microscope and expressions of Bcl-2 and Bax mRNAs in uterine tissue in the groups were detected with real-time fluorescent quantitative polymerase chain reaction(PCR) technique.RESULTS:After treatment,under microscope it was found that in the Lichong decoction group myometrium thinned,muscle fiber slightly overgrowth or long and thin,regular arrangement,inserting phenomenon of inner circular muscle and external longitudinal muscle was occasionally or not seen in the Lichong decoction group.The uterine coefficient and the uterine transverse diameter significantly decreased(P<0.01),and Bcl-2 mRNA expression significantly decreased(P<0.01) and Bax mRNA expression significantly increased in hysteromyoma tissue(P<0.01) in the Lichong decoction group as compared with the model group.CONCLUSION:Therapeutic effects of Lichong decoction on hysteromyoma is related with decrease of Bcl-2 mRNA expression and increase of Bax mRNA expression.展开更多
OBJECTIVE:To evaluate the effects of baicalin in human gastric cancer cells, including apoptosis-inducing effects, and to investigate its underlying mechanisms of action.METHODS:Cell proliferation and apoptosis assays...OBJECTIVE:To evaluate the effects of baicalin in human gastric cancer cells, including apoptosis-inducing effects, and to investigate its underlying mechanisms of action.METHODS:Cell proliferation and apoptosis assays were performed to investigate the anti-proliferation effects of baicalin in human gastric cancer BGC-823 and MGC-803 cells.Real time-quantitative polymerase chain reaction and Western blotting analysis were performed to elucidate the molecular mechanisms underlying the anti-tumor properties of baicalin.RESULTS:In BGC-823 and MGC-803 gastric cancer cells treated with 80, 120, and 160 μmol/L baicalin for 48 h, a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay showed that baicalin significantly inhibited cell proliferation in a dose-dependent manner, while flow cytometric analysis demonstrated that baicalin could induce apoptosis, also in a dose-dependent manner.Moreover, baicalin up-regulated the expression of caspase-3, caspase-9, and B cell lymphoma(Bcl-2)-associated X protein and down-regulated the expression of Bcl-2 at both the m RNA and protein level.CONCLUSION:Baicalin has potential as a therapeutic agent for gastric cancer by inducing apoptosis in cancer cells.展开更多
OBJECTIVE:To investigate the effects of icariin on apoptosis and the expression of Fas, Fas ligand(Fas L), B cell lymphoma(Bcl-2), and Bcl-2-associated X protein(Bax) in CD4+ T lymphocytes from patients with ankylosin...OBJECTIVE:To investigate the effects of icariin on apoptosis and the expression of Fas, Fas ligand(Fas L), B cell lymphoma(Bcl-2), and Bcl-2-associated X protein(Bax) in CD4+ T lymphocytes from patients with ankylosing spondylitis.METHODS:Primary cultures of peripheral blood CD4+ T lymphocytes were established and treated with icariin at high, medium, and low doses(0.5,0.25, and 0.125 mg/mL).Sulfasalazine treated and helthy cells were used as controls.Apoptosis of treated cells was determined by flow cytometry.Reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays were used to determine the effects of icariin on the expression of Fas, Fas L, Bcl-2, and Bax.The activity of caspase 8 and caspase 3 was determined by a colorimetric assay.RESULTS:The m RNA and protein expression of Fas,and activity of caspase 8 and caspase 3 in CD4+ T lymphocytes were increased by icariin(P < 0.05).Conversely, the m RNA and protein expression of Bcl-2 was decreased(P < 0.05).The expression of Fas L and Bax were not significantly different between groups.The proapoptotic effects of icariin were dose-dependent.CONCLUSION:Icariin induces the apoptosis of CD4 + T cells from patients with AS comparing to normal control.Therefore, the induction of apoptosis may be the likely mechanism of action of icariin's antirheumatics activities.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and fibrosis.Liver injury(LI)i...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and fibrosis.Liver injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated cholangiopathy.Mechanisms of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell invasion.AIM To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe COVID-19.METHODS ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel classifiers.RESULTS ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct cholangiocytes.Strikingly,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in cirrhosis.ACE2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD spectrum.Hepatic ACE2 levels are also increased in COVID-19 patients,especially those showing evidence of LI,but are not correlated with the presence of SARS-CoV-2 virus in the liver.However,there is a clear association between the hepatic lipid droplet content and the presence of the virus,suggesting a possible functional link.CONCLUSION Hepatic ACE2 levels were elevated in nonfibrotic MASH and COVID-19 patients with LI,while lipid accumulation may promote intra-hepatic SARS-CoV-2 replication,accelerating MASLD progression and COVID-19-mediated liver damage.展开更多
文摘BACKGROUND Special AT-rich sequence binding protein 2(SATB2)-associated syndrome(SAS;OMIM 612313)is an autosomal dominant disorder.Alterations in the SATB2 gene have been identified as causative.CASE SUMMARY We report a case of a 13-year-old Chinese boy with lifelong global developmental delay,speech and language delay,and intellectual disabilities.He had short stature and irregular dentition,but no other abnormal clinical findings.A de novo heterozygous nonsense point mutation was detected by genetic analysis in exon 6 of SATB2,c.687C>A(p.Y229X)(NCBI reference sequence:NM_001172509.2),and neither of his parents had the mutation.This mutation is the first reported and was evaluated as pathogenic according to the guidelines from the American College of Medical Genetics and Genomics.SAS was diagnosed,and special education performed.Our report of a SAS case in China caused by a SATB2 mutation expanded the genotype options for the disease.The heterogeneous manifestations can be induced by complicated pathogenic involvements and functions of SATB2 from reviewed literatures:(1)SATB2 haploinsufficiency;(2)the interference of truncated SATB2 protein to wild-type SATB2;and(3)different numerous genes regulated by SATB2 in brain and skeletal development in different developmental stages.CONCLUSION Global developmental delays are usually the initial presentations,and the diagnosis was challenging before other presentations occurred.Regular follow-up and genetic analysis can help to diagnose SAS early.Verification for genes affected by SATB2 mutations for heterogeneous manifestations may help to clarify the possible pathogenesis of SAS in the future.
基金Supported by Beijing City Natural Science Fund (No.7082015)National Natural Science Fund (No. 81073096)"Middle-young Aged Core Talent Cultural Plant" of Beijing City University Talent Strengthening Education Plant (No.PHR201008403)
文摘OBJECTIVE:To study on effects of Lichong decoction on expression of apoptosis-controlling genes,Bcl-2 and Bcl-2-associated X protein(Bax) mRNAs in hysteromyoma tissue of the hysteromyoma model rat.METHODS:Fifty Wistar female rats were randomly divided into a normal group,a model group,a Lichong decoction group,a Guizifuling capsule group and a Mifepristone group.The hysteromyoma rat model was established by intraperitoneal injection of exogenous estrin and progestogens.Pathological examination of uterine tissue,uterine coefficient and uterine transverse diameter were made under optic microscope and expressions of Bcl-2 and Bax mRNAs in uterine tissue in the groups were detected with real-time fluorescent quantitative polymerase chain reaction(PCR) technique.RESULTS:After treatment,under microscope it was found that in the Lichong decoction group myometrium thinned,muscle fiber slightly overgrowth or long and thin,regular arrangement,inserting phenomenon of inner circular muscle and external longitudinal muscle was occasionally or not seen in the Lichong decoction group.The uterine coefficient and the uterine transverse diameter significantly decreased(P<0.01),and Bcl-2 mRNA expression significantly decreased(P<0.01) and Bax mRNA expression significantly increased in hysteromyoma tissue(P<0.01) in the Lichong decoction group as compared with the model group.CONCLUSION:Therapeutic effects of Lichong decoction on hysteromyoma is related with decrease of Bcl-2 mRNA expression and increase of Bax mRNA expression.
基金Supported by the Natural Science Foundation of Gansu Province(No.148RJZA073)the Health Industry Scientific Research Project of Gansu Province(No.GWGL 2013-40)the Openning Plan Project of Key Laboratory for Transfer of Dunhuang Medicine at the Provincial and Ministerial Level(No.DHYX1213-008)
文摘OBJECTIVE:To evaluate the effects of baicalin in human gastric cancer cells, including apoptosis-inducing effects, and to investigate its underlying mechanisms of action.METHODS:Cell proliferation and apoptosis assays were performed to investigate the anti-proliferation effects of baicalin in human gastric cancer BGC-823 and MGC-803 cells.Real time-quantitative polymerase chain reaction and Western blotting analysis were performed to elucidate the molecular mechanisms underlying the anti-tumor properties of baicalin.RESULTS:In BGC-823 and MGC-803 gastric cancer cells treated with 80, 120, and 160 μmol/L baicalin for 48 h, a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay showed that baicalin significantly inhibited cell proliferation in a dose-dependent manner, while flow cytometric analysis demonstrated that baicalin could induce apoptosis, also in a dose-dependent manner.Moreover, baicalin up-regulated the expression of caspase-3, caspase-9, and B cell lymphoma(Bcl-2)-associated X protein and down-regulated the expression of Bcl-2 at both the m RNA and protein level.CONCLUSION:Baicalin has potential as a therapeutic agent for gastric cancer by inducing apoptosis in cancer cells.
基金Supported by the Fundamental Research Funds for the Central Public Welfare Research Institutes:Pharmacogenomics of Tripterygium wilfordii Hook F response and liver toxic reaction in Rheumatoid Arthritis(No.ZZ0708079)the Fundamental Research Funds for the Central Public Welfare Research Institutes Pharmacogenomics of Tripterygium wilfordii Hook F response reaction in Rheumatoid Arthritis(No.31470962)
文摘OBJECTIVE:To investigate the effects of icariin on apoptosis and the expression of Fas, Fas ligand(Fas L), B cell lymphoma(Bcl-2), and Bcl-2-associated X protein(Bax) in CD4+ T lymphocytes from patients with ankylosing spondylitis.METHODS:Primary cultures of peripheral blood CD4+ T lymphocytes were established and treated with icariin at high, medium, and low doses(0.5,0.25, and 0.125 mg/mL).Sulfasalazine treated and helthy cells were used as controls.Apoptosis of treated cells was determined by flow cytometry.Reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays were used to determine the effects of icariin on the expression of Fas, Fas L, Bcl-2, and Bax.The activity of caspase 8 and caspase 3 was determined by a colorimetric assay.RESULTS:The m RNA and protein expression of Fas,and activity of caspase 8 and caspase 3 in CD4+ T lymphocytes were increased by icariin(P < 0.05).Conversely, the m RNA and protein expression of Bcl-2 was decreased(P < 0.05).The expression of Fas L and Bax were not significantly different between groups.The proapoptotic effects of icariin were dose-dependent.CONCLUSION:Icariin induces the apoptosis of CD4 + T cells from patients with AS comparing to normal control.Therefore, the induction of apoptosis may be the likely mechanism of action of icariin's antirheumatics activities.
基金Supported by University of Edinburgh Hepatology Laboratory Internal Fundingthe Liver Endowment Funds of the Edinburgh&Lothian Health Foundation.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and fibrosis.Liver injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated cholangiopathy.Mechanisms of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell invasion.AIM To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe COVID-19.METHODS ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel classifiers.RESULTS ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct cholangiocytes.Strikingly,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in cirrhosis.ACE2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD spectrum.Hepatic ACE2 levels are also increased in COVID-19 patients,especially those showing evidence of LI,but are not correlated with the presence of SARS-CoV-2 virus in the liver.However,there is a clear association between the hepatic lipid droplet content and the presence of the virus,suggesting a possible functional link.CONCLUSION Hepatic ACE2 levels were elevated in nonfibrotic MASH and COVID-19 patients with LI,while lipid accumulation may promote intra-hepatic SARS-CoV-2 replication,accelerating MASLD progression and COVID-19-mediated liver damage.
