1.Post-translational modifications of collagen and its related diseases in metabolic pathways.
Linghong GUO ; Weiyi XIANG ; Zhaoping PAN ; He GU ; Xian JIANG
Acta Pharmaceutica Sinica B 2025;15(4):1773-1795
As the most abundant and essential structural protein in the human body, collagen is ubiquitously present in the interstitium of nearly all solid organs, playing a crucial role in maintaining the structural integrity and functional stability of human tissues and organs. Disorders associated with collagen structure and metabolisms impose a significant burden on society and healthcare systems. Post-translational modifications (PTMs) are essential steps in collagen metabolism, and recent studies have indicated that aberrant regulation of PTMs plays a pivotal role in the pathogenesis and progress of collagen-related disorders, including liver, kidney, heart, lung, and skin fibrosis, as well as keloid. This review provides a comprehensive summary of the regulatory mechanisms of both traditional and novel PTMs in collagen metabolism and collagen-related diseases. Furthermore, we summarize the drugs that modulate PTMs and their effects, with the aim of elucidating the pathophysiology of collagen-related diseases and provide new insights for their diagnosis, prevention, and treatment.
2.Relationship between abnormal expression of serum NGB and MBP and the cerebral neurodevelopment of neonates with HIE
Bihai HE ; Nini ZHANG ; Nannan SHI ; Caihong SONG ; Zhaoping HE ; Xin LI
International Journal of Laboratory Medicine 2025;46(7):796-800
Objective To analyze the relationship between abnormal expression of serum neurohemoglobin(NGB)and myelin basic protein(MBP)and the cerebral neurodevelopment of neonates with hypoxic-ischemic encephalopathy(HIE).Methods A total of 89 preterm infants with HIE admitted in the hospital between January 2023 and March 2024 were selected as the observation group,and 60 preterm infants without HIE during the same period were selected as the control group.Serum levels of MBP,NGB and secretagogues in two groups were detected,and the neonates amplitude integration electroencephalogram score was evaluated.The neurological function of neonates was evaluated using 20 items of Neonatal Behavioral Neurological As-sessment(NBNA).The correlation test and diagnostic value were evaluated using Spearman method and re-ceiver operating characteristic(ROC)curve.Results The serum levels of NGB,MBP and secretagogue in the ob-servation group were higher than those in the control group(P<0.05),and the amplitude integration electroencepha-logram score was lower than that in the control group(P<0.05).The serum MBP,NGB and secretagogue levels in the mild,moderate,and severe groups increased sequentially(P<0.05),NBNA score and amplitude integration e-lectroencephalogram score decreased sequentially(P<0.05).The levels of NGB,MBP and secretagogue were the risk factors affecting NBNA score(P<0.05),and the amplitude integration electroencephalogram score was a protective factor affecting NBNA score(P<0.05).The area under the curve of NGB and MBP in diag-nosing HIE was greater than 0.8,which had high application value.Conclusion Serum NGB and MBP levels are closely related to the severity of HIE,and have certain connection with NBNA score.Elevated levels of NGB and MBP in neonates with HIE may be related to the body's stress response to nerve damage,which could reflect to some extent the brain nerve function damage in with HIE.
3.Influence of Age and Type 1 Diabetes Mellitus on Serological Test for Celiac Disease in Children
Anshu MAHESHWARI ; Zhaoping HE ; Melissa Nicole WEIDNER ; Patrick LIN ; Ryan BOBER ; Fernando J. DEL ROSARIO
Pediatric Gastroenterology, Hepatology & Nutrition 2021;24(2):218-229
Purpose:
Serological tests of tissue transglutaminase (TTG) and deamidated gliadin (DGP) antibodies for celiac disease diagnosis show conflicting correlation with histology in young children and in type 1 diabetes mellitus (T1DM). Tests' ability to predict histology and cutoff values based on age and T1DM was evaluated.
Methods:
A retrospective study of children who had celiac serological tests between 6/1/2002 and 12/31/2014 at a pediatric hospital.
Results:
TTG IgA displayed similar results in predicting histology between <4.0 and ≥4.0 years age groups with sensitivity 98% and 93%, and specificity 88% and 86%, respectively. In children <4.0 years old, sensitivity for DGP antibodies was 100% and specificity 94%; in ≥4.0 years age groups, sensitivity was 60%, 88% for DGP IgA and IgG and specificity 95%, 96%, respectively. TTG IgA had low specificity in patients with T1DM compared with non-T1DM, 42% vs. 91%. Positive TTG IgA with normal histology was associated with higher T1DM prevalence at 36% compared with negative tests at 4%. Finally, the TTG IgA cutoff value was higher in T1DM at 36 vs. 16.3 units in non-T1DM. DGP IgG cutoff showed similar values between age groups; TTG IgA and DGP IgA cutoffs were lower in <4.0 years at 8.3 and 11.9 units than ≥4.0 years at 23.4 and 19.9, respectively.
Conclusion
TTG IgA is sufficient for the <4.0 years age group and DGP antibodies had no advantage over TTG IgA in older children. The cutoff value to determine a positive TTG IgA should be higher for children with T1DM.
4.The PNPLA3 rs738409 Variant but not MBOAT7 rs641738 is a Risk Factor for Nonalcoholic Fatty Liver Disease in Obese U.S. Children of Hispanic Ethnicity
Sana MANSOOR ; Anshu MAHESHWARI ; Matthew Di GUGLIELMO ; Katryn FURUYA ; Makala WANG ; Erin CROWGEY ; Zarela MOLLE-RIOS ; Zhaoping HE
Pediatric Gastroenterology, Hepatology & Nutrition 2021;24(5):455-469
Purpose:
The rs641738 C>T in membrane-bound O-acyltransferase domain-containing protein 7 (MBOAT7) is implicated, along with the rs738409 C>G polymorphism in patatin-like phospholipase domain-containing protein 3 (PNPLA3), in nonalcoholic fatty liver disease (NAFLD). The association of these polymorphisms and NAFLD are investigated in Hispanic children with obesity.
Methods:
Obese children with and without NAFLD were enrolled at a pediatric tertiary care health system and genotyped for MBOAT7 rs641738 C>T and PNPLA3 rs738409 C>G. NAFLD was characterized by the ultrasonographic presence of hepatic steatosis along with persistently elevated liver enzymes. Genetic variants and demographic and biochemical data were analyzed for the effects on NAFLD.
Results:
Among 126 enrolled subjects, 84 in the case group had NAFLD and 42 in the control group did not. The two groups had similar demographic distribution. NAFLD was associated with abnormal liver enzymes and elevated triglycerides and cholesterol (p<0.05). Children with NAFLD had higher percentage of PNPLA3 GG genotype at 70.2% versus 31.0% in non-NAFLD, and lower MBOAT7 TT genotype at 4.8% versus 16.7% in non-NAFLD (p<0.05). PNPLA3 rs738409 C>G had an additive effect in NAFLD; however, MBOAT7 rs641738 C>T had no effects alone or synergistically with PNPLA3 polymorphism. NAFLD risk increased 3.7-fold in subjects carrying PNPLA3 GG genotype and decreased in MBOAT7 TT genotype.
Conclusion
In Hispanic children with obesity, PNPLA3 rs738409 C>G polymorphism increased the risk for NAFLD. The role of MBOAT7 rs641738 variant in NAFLD is less evident.
5.Influence of Age and Type 1 Diabetes Mellitus on Serological Test for Celiac Disease in Children
Anshu MAHESHWARI ; Zhaoping HE ; Melissa Nicole WEIDNER ; Patrick LIN ; Ryan BOBER ; Fernando J. DEL ROSARIO
Pediatric Gastroenterology, Hepatology & Nutrition 2021;24(2):218-229
Purpose:
Serological tests of tissue transglutaminase (TTG) and deamidated gliadin (DGP) antibodies for celiac disease diagnosis show conflicting correlation with histology in young children and in type 1 diabetes mellitus (T1DM). Tests' ability to predict histology and cutoff values based on age and T1DM was evaluated.
Methods:
A retrospective study of children who had celiac serological tests between 6/1/2002 and 12/31/2014 at a pediatric hospital.
Results:
TTG IgA displayed similar results in predicting histology between <4.0 and ≥4.0 years age groups with sensitivity 98% and 93%, and specificity 88% and 86%, respectively. In children <4.0 years old, sensitivity for DGP antibodies was 100% and specificity 94%; in ≥4.0 years age groups, sensitivity was 60%, 88% for DGP IgA and IgG and specificity 95%, 96%, respectively. TTG IgA had low specificity in patients with T1DM compared with non-T1DM, 42% vs. 91%. Positive TTG IgA with normal histology was associated with higher T1DM prevalence at 36% compared with negative tests at 4%. Finally, the TTG IgA cutoff value was higher in T1DM at 36 vs. 16.3 units in non-T1DM. DGP IgG cutoff showed similar values between age groups; TTG IgA and DGP IgA cutoffs were lower in <4.0 years at 8.3 and 11.9 units than ≥4.0 years at 23.4 and 19.9, respectively.
Conclusion
TTG IgA is sufficient for the <4.0 years age group and DGP antibodies had no advantage over TTG IgA in older children. The cutoff value to determine a positive TTG IgA should be higher for children with T1DM.
6.The PNPLA3 rs738409 Variant but not MBOAT7 rs641738 is a Risk Factor for Nonalcoholic Fatty Liver Disease in Obese U.S. Children of Hispanic Ethnicity
Sana MANSOOR ; Anshu MAHESHWARI ; Matthew Di GUGLIELMO ; Katryn FURUYA ; Makala WANG ; Erin CROWGEY ; Zarela MOLLE-RIOS ; Zhaoping HE
Pediatric Gastroenterology, Hepatology & Nutrition 2021;24(5):455-469
Purpose:
The rs641738 C>T in membrane-bound O-acyltransferase domain-containing protein 7 (MBOAT7) is implicated, along with the rs738409 C>G polymorphism in patatin-like phospholipase domain-containing protein 3 (PNPLA3), in nonalcoholic fatty liver disease (NAFLD). The association of these polymorphisms and NAFLD are investigated in Hispanic children with obesity.
Methods:
Obese children with and without NAFLD were enrolled at a pediatric tertiary care health system and genotyped for MBOAT7 rs641738 C>T and PNPLA3 rs738409 C>G. NAFLD was characterized by the ultrasonographic presence of hepatic steatosis along with persistently elevated liver enzymes. Genetic variants and demographic and biochemical data were analyzed for the effects on NAFLD.
Results:
Among 126 enrolled subjects, 84 in the case group had NAFLD and 42 in the control group did not. The two groups had similar demographic distribution. NAFLD was associated with abnormal liver enzymes and elevated triglycerides and cholesterol (p<0.05). Children with NAFLD had higher percentage of PNPLA3 GG genotype at 70.2% versus 31.0% in non-NAFLD, and lower MBOAT7 TT genotype at 4.8% versus 16.7% in non-NAFLD (p<0.05). PNPLA3 rs738409 C>G had an additive effect in NAFLD; however, MBOAT7 rs641738 C>T had no effects alone or synergistically with PNPLA3 polymorphism. NAFLD risk increased 3.7-fold in subjects carrying PNPLA3 GG genotype and decreased in MBOAT7 TT genotype.
Conclusion
In Hispanic children with obesity, PNPLA3 rs738409 C>G polymorphism increased the risk for NAFLD. The role of MBOAT7 rs641738 variant in NAFLD is less evident.
7.Isolation, Purification and Characterization of Human Serum Apolipoprotein A Ⅰ
Zhaoping LIU ; Lili LIU ; Jiashan SHEN ; Xiangkun HE ; Shen XIANG ; Zhiwu AI
Chinese Journal of Primary Medicine and Pharmacy 2010;17(14):1937-1938,后插1
Objective To explore a method to separate and purify apolipoprotein Ⅰ from human serum conveniently and efficiently. Methods Apolipoprotein Ⅰ was separated and pufified by ultracentrifugation and affinity chromatography. Then the purified apolipoprotein Ⅰ was analyzed by SDS-polyacrylamide gel electrophoresis and agar gel double immunodiffusion test. Results The purified apolipoprotein Ⅰ was satisfactory. Conclusion This method had good reliability and was convenient and economical.
8.Study of ultrastructure and expression of epidermal growth factor receptor in placenta in intrahepatic cholestasis of pregnancy
Huiyan WANG ; Yaqin JIANG ; Zhaoping WANG ; Fenglin HE ; Changfen XU ; Li LUO ; Huan GE
Chinese Journal of Perinatal Medicine 2003;0(06):-
Objective The cytotoxic effect of bile acids on trophoblast and fetal development in intrahepatic cholestasis of pregnancy(ICP) were studied through the observation of ultrastructure changes and expression of epidermal growth factor receptor(EGFR) of placenta. Methods Twenty two ICP (7 with FGR and 15 without FGR) and 15 normal late pregnancies were selected. The placental ultrastructure was observed with transmission electron microscope. The expression of EGFR in placenta was determined by immunohistological method and the related quantity of EGFR mRNA was analysed by reverse transcription polymerase chain reaction (RT PCR). Results The morphological changes found in syncytiotrophoblast were the following: decrease in the number of superficial microvilli, dilatation of rough endoplasmic reticulum, tumefation or myelination of the mitochondria and abnormal distribution of chromatin. These changes of syncytiotrophoblast were more obvious in ICP with FGR. In addition, decrease in the number of capillaries and proliferation of degenerated collagenous fibrils in villi interstitium were also observed. Compared with the normal pregnancies, the expression of EGFR in placenta from ICP decreased significantly and there was no significant difference of EGFR expression in ICP with and without FGR. Conclusion Bile acids cause distinct injuries on trophoblast in a dose dependent manner and that maybe account for the decreased expression of placental EGFR in ICP.
9.Expression of Cell Cycle Related Factors Cyclin D1,CDK4,P16~(MTS1) and PRb in Condyloma Acuminatum
Fu DAI ; Maorong ZHENG ; Jin GUO ; Yuchen XIE ; Wenli LIU ; Zhaoping LV ; Li HE ; Dongju SUN ;
Chinese Journal of Dermatology 1995;0(04):-
Objective To investigate the expression and im plication of cell-cycle related factors(Cyclin D1,CDK4,P16 MTS1 and PRb)in condyloma acuminatum(CA).Methods The expression and distribution of cyclin D1,CDK4,P16 MTS1 and PRb were detected by immunohisto chemical technique streptavidin peroxidase(SP)in 27cases of HPV6/11positive CA that were confirmed by PCR and 10cases of norm al skins(foreskins).Results①Cyclin D1was not expressed in both normal skin and lesions of CA.②The intensity of expression of CDK4was 2.19in the basal cells in the lesions of CA,which was significantly weaker than that in normal skin(4.8,P

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