1.Preliminary study of glyceryl phenylbutyrate therapy for Ornithine transcarbamylase deficiency and a literature review.
Duo ZHOU ; Xiaohong SHANG ; Yu QIAO ; Yi CHENG ; Zinan YU ; Xinwen HUANG
Chinese Journal of Medical Genetics 2023;40(9):1107-1112
OBJECTIVE:
To evaluate the efficacy and safety of glyceryl phenylbutyrate (GPB) therapy for patients with Ornithine transcarbamylase deficiency (OTCD).
METHODS:
Two children with OTCD were selected as the study subjects, and their clinical manifestations, blood ammonia, liver enzymes, growth and development information following the treatment with GPB were retrospectively analyzed. A literature review was also carried out by searching the PubMed database for studies on the GPB treatment for urea cycle disorders.
RESULTS:
With the GPB treatment, the blood ammonia and liver enzyme level in both patients have decreased to the normal range within 3 months. Motor development in child 2 has improved. No adverse reaction was noted, except for transient palmar greasy smell and loss of appetite in child 1. Analysis of the literature showed that patients had lower ammonia exposure, lower annual incidence of hyperammonemic crisis, more actual protein intake and fewer adverse events during GPB treatment.
CONCLUSION
GPB is safe and effective for the treatment of OTCD.
Child
;
Humans
;
Ornithine Carbamoyltransferase Deficiency Disease/drug therapy*
;
Phenylbutyrates/therapeutic use*
;
Ammonia
;
Retrospective Studies
2.Advanced glycated albumin induces macrophage apoptosis via activating caspase-12 pathway.
Jin-Guo LI ; Qi HAO ; Ying-Xue LIU ; Peng LI ; Peng LI ; Xia-Yan SHAO ; Hua TIAN ; Yong-Qi FANG ; Shu-Tong YAO
Acta Physiologica Sinica 2016;68(6):733-739
The purpose of the present study was to investigate the effect of advanced glycated albumin (AGE-alb) on the activation of caspase-12, a key molecule in endoplasmic reticulum stress (ERS)-associated apoptotic pathway, and to elucidate the underlying molecular mechanisms of macrophage apoptosis. RAW264.7 macrophages were treated with AGE-alb (2, 4 and 6 g/L), control albumin (C-alb, 4 g/L), tunicamycin (TM, 4 mg/L), or pretreated with 4-phenylbutyric acid (PBA, 5 mmol/L) for 1 h and then treated with AGE-alb (4 g/L). After incubation for 24 h, the cell viability and apoptosis were determined by using MTT assay and TUNEL detection kit, respectively. Lactate dehydrogenase (LDH) activity in media was determined by using an assay kit. The protein levels of caspase-12 were examined by Western blot analysis. The results showed that like TM (an ERS inducer), incubation with AGE-alb led to significant decrease in viability and increase in LDH activity in media and apoptotic rate in a dose-dependent manner. In addition, AGE-alb induced activation of caspase-12 especially at the concentration of 4 and 6 g/L (P < 0.01), which was similar to TM. However, PBA (an ERS inhibitor) protected RAW264.7 macrophages from AGE-alb-induced decrease in viability and increases in LDH activity and apoptosis. Moreover, PBA also inhibited the caspase-12 activation induced by AGE-alb (P < 0.05). These results suggest that AGE-alb may induce apoptosis in RAW 264.7 macrophages, and the mechanism may be related to the activation of ERS-associated apoptotic pathway mediated by caspase-12.
Animals
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Apoptosis
;
Caspase 12
;
Cell Line, Tumor
;
Cell Survival
;
Endoplasmic Reticulum Stress
;
Macrophages
;
Mice
;
Phenylbutyrates
;
Serum Albumin
;
Tunicamycin
3.4-phenylbutyric Acid Regulates Collagen Synthesis and Secretion Induced by High Concentrations of Glucose in Human Gingival Fibroblasts.
Geum Hwa LEE ; Hyo Won OH ; Hyun Dae LIM ; Wan LEE ; Han Jung CHAE ; Hyung Ryong KIM
The Korean Journal of Physiology and Pharmacology 2011;15(6):345-351
High glucose leads to physio/pathological alterations in diabetes patients. We investigated collagen production in human gingival cells that were cultured in high concentrations of glucose. Collagen synthesis and secretion were increased when the cells were exposed to high concentrations of glucose. We examined endoplasmic reticulum (ER) stress response because glucose metabolism is related to ER functional status. An ER stress response including the expression of glucose regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), inositol requiring enzyme alpha (IRE-1alpha) and phosphoreukaryotic initiation factor alpha (p-eIF-2alpha) was activated in the presence of high glucose. Activating transcription factor 4 (ATF-4), a downstream protein of p-eIF-2alpha as well as a transcription factor for collagen, was also phosphorylated and translocalized into the nucleus. The chemical chaperone 4-PBA inhibited the ER stress response and ATF-4 phosphorylation as well as nuclear translocation. Our results suggest that high concentrations of glucose-induced collagen are linked to ER stress and the associated phosphorylation and nuclear translocation of ATF-4.
Activating Transcription Factor 4
;
Butylamines
;
Collagen
;
Endoplasmic Reticulum
;
Fibroblasts
;
Glucose
;
Humans
;
Inositol
;
Peptide Initiation Factors
;
Phenylbutyrates
;
Phosphorylation
;
Transcription Factors
4.Endoplasmic reticulum stress mediates lipopolysaccharide-induced apoptosis in rat hepatocyte.
Ying-Lei JI ; Jun YAN ; Yan-Sha WANG ; Yi-Chang LIU ; Zhen-Yong GU
Journal of Forensic Medicine 2014;30(1):13-18
OBJECTIVE:
To investigate the role of endoplasmic reticulum stress (ERS) in lipopolysaccharide (LPS)-induced hepatocyte apoptosis.
METHODS:
Cells of the rat hepatocyte line BRL were cultured. The hepatocytes were treated with LPS, ERS inducer thapsigargin (TG), and ERS inhibitor 4-phenylbutyric acid (4-PBA), respectively or in their different combination. The cell viability was measured by MTT assay. The cyto-nuclear morphological changes of apoptosis cells were detected by the fluorescent dye Hoechst 33258. The apoptosis rate was assessed by flow cytometry with Annexin V-FITC/PI double-staining. Expressions of GRP78 as ERS marker protein, CHOP, caspase-12 and cleaved-caspase-3 as ERS related protein were detected by Western blotting.
RESULTS:
LPS could cause a decrease in cell viability and an increase in apoptosis rate in a dose- and time-dependent manner. The expression of GRP78, CHOP, caspase-12 and cleaved-caspase-3 proteins were significantly increased with LPS treatment. TG led to a marked decrease in cell viability and an increase in apoptosis rate, which aggravated the hepatocyte injury induced by LPS; whereas 4-PBA alleviated LPS-induced apoptosis.
CONCLUSION
ERS mediates LPS-induced hepatocyte injuries, indicating that ERS may play a vital role in the pathogenesis of LPS-induced hepatocyte injuries.
Animals
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Apoptosis
;
Caspase 3
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Cell Survival
;
Endoplasmic Reticulum Chaperone BiP
;
Endoplasmic Reticulum Stress
;
Heat-Shock Proteins
;
Hepatocytes
;
Lipopolysaccharides
;
Phenylbutyrates
;
Rats
5.Analysis of adult vaccination in Shandong Province from 2018 to 2022.
Wei Yan ZHANG ; Ren Peng LI ; Yang YU ; Ying Jie ZHANG ; Hui Feng SUN ; Ai Qiang XU
Chinese Journal of Preventive Medicine 2023;57(12):2021-2028
Objective: To analyze the utilization of adult vaccination among people aged 18 and above in Shandong Province from 2018 to 2022. Methods: Data on vaccination units in 2022 and individual cases of vaccination information for people aged 18 and above were extracted from the Shandong Immunization Information System. A descriptive analysis was conducted on the distribution of adult vaccination units and adult vaccination varieties. The total vaccination amount and vaccination rate were calculated. Results: By the end of 2022, there were 3 948 vaccination units providing adult vaccination in Shandong Province, with 0.36 adult vaccination clinics per 10 000 people. Adult vaccination including RabV(rabies vaccine for human use), InfV(influenza vaccine), HPV(human papillomavirus), HepB(hepatitis B vaccine), PPV23(23-valent pneumococcal polysaccharide vaccine), MenACYW135(meningococcal polysaccharide vaccine group ACYW135), MMR(measles, mumps and rubella combined attenuated live vaccine), HEV(hepatitise E vaccine), RZV(recombinant zoster vaccine), TV(tetanus vaccine) and HF(haemorrhagic fever with renal syndrome vaccine) vaccines were administered, with a cumulative dose of 40.056 9 million and an average of 0.1 doses per person per year from 2018 to 2022. The top three vaccines were RabV, InfV and HPV, accounting for 31.48%, 22.57%, and 15.93% of the total vaccination amount, respectively. The annual vaccination dose for adults increased from 3.477 3 million in 2018 to 13.308 6 million in 2022, with an average annual growth rate of 56.55%. The cumulative 5-year doses of RabV and TV were 15.90 doses per 100 people and 0.21 doses per 100 people. The average annual vaccination rate of InfV was 2.28%. The cumulative full vaccination rates of HPV, HepB, PPV23 and RZV were 12.44%, 1.61%, 0.52% and 0.17%, respectively. The cumulative 5-year doses of RabV and TV were 29.19 doses per 100 people and 0.43 doses per 100 people in the age group of 20 to<30 years old. The vaccination rates of InfV and PPV23 were 9.08% and 1.27% in the age group of 70 to<80 years old. The vaccination rate of RZV was 0.11% in the age group of 50 to<60 years old. The HPV vaccination rate was 18.09% in the age group of 20 to<30 years old, and the HepB, MenACYW135, MMR and HEV vaccination rates were 6.21%, 9.55%, 2.65%, and 2.83% in the 18-19 age group, respectively. Conclusion: There are relatively few types of adult vaccination in Shandong Province, with narrow coverage and low vaccination rates.
Adult
;
Humans
;
Young Adult
;
Aged
;
Middle Aged
;
Adolescent
;
Aged, 80 and over
;
Papillomavirus Infections
;
Vaccination
;
Phenylbutyrates
;
Influenza Vaccines
6.Analysis of adult vaccination in Shandong Province from 2018 to 2022.
Wei Yan ZHANG ; Ren Peng LI ; Yang YU ; Ying Jie ZHANG ; Hui Feng SUN ; Ai Qiang XU
Chinese Journal of Preventive Medicine 2023;57(12):2021-2028
Objective: To analyze the utilization of adult vaccination among people aged 18 and above in Shandong Province from 2018 to 2022. Methods: Data on vaccination units in 2022 and individual cases of vaccination information for people aged 18 and above were extracted from the Shandong Immunization Information System. A descriptive analysis was conducted on the distribution of adult vaccination units and adult vaccination varieties. The total vaccination amount and vaccination rate were calculated. Results: By the end of 2022, there were 3 948 vaccination units providing adult vaccination in Shandong Province, with 0.36 adult vaccination clinics per 10 000 people. Adult vaccination including RabV(rabies vaccine for human use), InfV(influenza vaccine), HPV(human papillomavirus), HepB(hepatitis B vaccine), PPV23(23-valent pneumococcal polysaccharide vaccine), MenACYW135(meningococcal polysaccharide vaccine group ACYW135), MMR(measles, mumps and rubella combined attenuated live vaccine), HEV(hepatitise E vaccine), RZV(recombinant zoster vaccine), TV(tetanus vaccine) and HF(haemorrhagic fever with renal syndrome vaccine) vaccines were administered, with a cumulative dose of 40.056 9 million and an average of 0.1 doses per person per year from 2018 to 2022. The top three vaccines were RabV, InfV and HPV, accounting for 31.48%, 22.57%, and 15.93% of the total vaccination amount, respectively. The annual vaccination dose for adults increased from 3.477 3 million in 2018 to 13.308 6 million in 2022, with an average annual growth rate of 56.55%. The cumulative 5-year doses of RabV and TV were 15.90 doses per 100 people and 0.21 doses per 100 people. The average annual vaccination rate of InfV was 2.28%. The cumulative full vaccination rates of HPV, HepB, PPV23 and RZV were 12.44%, 1.61%, 0.52% and 0.17%, respectively. The cumulative 5-year doses of RabV and TV were 29.19 doses per 100 people and 0.43 doses per 100 people in the age group of 20 to<30 years old. The vaccination rates of InfV and PPV23 were 9.08% and 1.27% in the age group of 70 to<80 years old. The vaccination rate of RZV was 0.11% in the age group of 50 to<60 years old. The HPV vaccination rate was 18.09% in the age group of 20 to<30 years old, and the HepB, MenACYW135, MMR and HEV vaccination rates were 6.21%, 9.55%, 2.65%, and 2.83% in the 18-19 age group, respectively. Conclusion: There are relatively few types of adult vaccination in Shandong Province, with narrow coverage and low vaccination rates.
Adult
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Humans
;
Young Adult
;
Aged
;
Middle Aged
;
Adolescent
;
Aged, 80 and over
;
Papillomavirus Infections
;
Vaccination
;
Phenylbutyrates
;
Influenza Vaccines
7.Inhibitory effect of ONO-AE3-208 on the formation of bone metastasis of prostate cancer in mice.
Song XU ; Jing-Ping GE ; Wen-Quan ZHOU ; Zheng-Yu ZHANG
National Journal of Andrology 2014;20(8):684-689
OBJECTIVETo examine the effect of ONO-AE3-208, an EP4 antagonist, on the formation of bone metastasis from prostate cancer in mice.
METHODSThirty-four 6-week old nude mice were divided into an experimental and a control group of equal number to be treated by intraperitoneal injection of ONO-AE3-208 and double distilled water, respectively. Then PC3/LUC cells were constructed by stably transfecting luciferin to prostate cancer PC3 cells and inoculated into the left ventricle of the mice to establish an animal model of systemic bone metastasis. The time of metastasis formation, photon tumor burdens, and changes of the survival curves after modeling were compared between the two groups of mice.
RESULTSAt 30 days after modeling, bioluminescence imaging analysis showed that the photon tumor burdens were significantly increased in a time-dependent manner in the control group in comparison with those in the experimental group (P < 0.01). The rate of metastasis formation was significantly higher in the former than in the latter (93.3% vs 33.3%, P < 0.001). The median time of metastasis formation was 29 d (95% CI 26.547 - 35.262) in the experimental animals as compared with 21 d (95% CI 17.213 -24.787) in the controls (P < 0.001).
CONCLUSIONEP4 antagonist ONO-AE3-208 can inhibit the formation of bone metastasis from prostate cancer in mice.
Animals ; Bone Neoplasms ; prevention & control ; secondary ; Cell Line, Tumor ; Disease Models, Animal ; Humans ; Male ; Mice ; Mice, Nude ; Naphthalenes ; pharmacology ; Neoplasms, Experimental ; prevention & control ; Phenylbutyrates ; pharmacology ; Prostatic Neoplasms ; pathology
8.Effect of phenylbutyrate, a histone deacetylase inhibitor, on differentiation and apoptosis of Kasumi-1 cells.
Chang-lai HAO ; Ke-jing TANG ; Zheng TIAN ; Hai-yan XING ; Min WANG ; Jian-xiang WANG
Chinese Journal of Hematology 2003;24(5):241-244
OBJECTIVETo explore the blockade effect of phenylbutyrate (PB), a histone deacetylase inhibitor, on the in vitro biological function of AML1/ETO to reverse its transcription repression and induce Kasumi-1 cells to differentiate and apoptosis.
METHODSKasumi-1 cells were treated with PB at different concentrations in suspension culture. Cell proliferation was analysed by MTT assay, morphological changes by light and electron microscopy, expression of myeloid-specific differentiation antigen and cell cycle by flow cytometry, cell apoptosis by annexin V staining, agarose gel electrophoresis and flow cytometry.
RESULTSPB treatment caused a dose-dependent inhibition of the cell proliferation. The IC(50) was about 2.3 mmol/L. PB treatment led to a progressive decline in the fraction of S-phase cells and increase in G(0)/G(1) cells. PB induced a time- and dose-dependent increase in expression of myeloid cell surface protein CD(11b) and CD(13). A dose-dependent increase in early apoptosis for 2 days treatment, late apoptosis for 3 days treatment. The DNA ladder of apoptosis was observed on agarose gel electrophoresis for 5 days treatment. Morphological features of monocytoid differentiation and apoptosis were seen on Wright-Giemsa staining smears.
CONCLUSIONPB treatment could inhibit proliferation of Kasumi-1 cells, induce partial differentiation, apoptosis and accumulation of cells in G(0)/G(1) phase.
Apoptosis ; drug effects ; Cell Differentiation ; drug effects ; Cell Division ; drug effects ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Histone Deacetylase Inhibitors ; Humans ; Leukemia, Myeloid, Acute ; pathology ; Phenylbutyrates ; pharmacology
9.Sodium 4-phenylbutyrate Attenuates High-fat Diet-induced Impaired Spermatogenesis.
Er Hui WANG ; San Qiao YAO ; Ling TAO ; Jin Yan XI
Biomedical and Environmental Sciences 2018;31(12):876-882
OBJECTIVE:
To determine the mitigating effects of sodium 4-phenylbutyrate (4-PBA) on high-fat diet (HFD)-induced spermatogenesis dysfunction.
METHODS:
Male rats (n = 30) were randomly divided into three groups: control, HFD, and 4-PBA (HFD +4-PBA). After 13 weeks, rats were euthanized. Testes and epididymis were harvested for further analysis. Sex hormones were detected, and hematoxylin and eosin staining was performed to examine the histological changes in the testes. Semen samples were collected to evaluate sperm quality. Spermatogenic cell apoptosis was detected by TUNEL assay.
RESULTS:
Compared with the control group, the final body weight and body weight gain were significantly higher in HFD-fed rats, while the testicle/body weight ratios were lower (P < 0.05). In HFD-fed rats, obvious pathological changes in the testicular tissue were observed. Treatment with 4-PBA attenuated HFD-induced histological damage, ameliorated the HFD-induced decrease in serum testosterone (T), and reduced the rate of testicular cell apoptosis (P < 0.05) in obese male rats. Finally, 4-PBA significantly improved semen parameters in HFD rats (P < 0.05).
CONCLUSION
HFD exposure induced detrimental effects on spermatogenesis, semen quality, serum T level, and testicular cell apoptosis in rats. Treatment with 4-PBA ameliorated HFD?induced impaired spermatogenesis via inhibition of apop-tosis in rats. 4-PBA may have therapeutic value in the treatment of obesity?related impairment of spermatogenesis.
Animals
;
Diet, High-Fat
;
adverse effects
;
Male
;
Phenylbutyrates
;
pharmacology
;
Rats, Sprague-Dawley
;
Semen Analysis
;
Spermatogenesis
;
drug effects
;
Testis
;
drug effects
;
pathology
;
Testosterone
;
blood
10.A randomized controlled trial of indobufen versus aspirin in the prevention of bridging restenosis after coronary artery bypass grafting.
Chen BAI ; Jing Xing LI ; Yang YU ; Rui LIU ; Ming Xin GAO ; Fan ZHANG ; Hai Yang LI
Chinese Journal of Cardiology 2022;50(5):466-470
Objective: To compare the efficacy and safety between indobufen and aspirin in the prevention of restenosis of bridge vessels at 1 year after off-pump coronary artery bypass grafting. Methods: This study was a prospective cohort study. We selected 152 patients who received coronary artery bypass grafting in Beijing Anzhen Hospital from December 2016 to December 2018. Patients were divided into the indobufen group and the aspirin group. Patients in the aspirin group were treated with aspirin and clopidogrel, and patients in the indobufen group were treated with indobufen and clopidogrel. During the 1-year follow-up, the rate of restenosis of saphenous vein bridge and internal mammary artery bridge, the rate of adverse cardiac events and adverse reactions were compared between the two groups. The levels of fibrinogen (FIB), D-dimer (D-D), thrombomodulin (TM) and thrombin-activatable fibrinolysis inhibitor (TAFI) were compared before and after antiplatelet therapy. Results: There were 76 cases in the indobufen group, including 57 males (75.0%), aged (60.3±6.6) years. There were 76 cases in the aspirin group, including 62 males (81.6%), aged (59.7±7.2) years. Baseline data were comparable between the two groups (P>0.05). During the follow-up, 3 cases were lost to follow up. Follow-up was completed in 74 patients in the indobufen group and 75 in the aspirin group. A total of 268 bridging vessels were grafted in the indobufen group and 272 in the aspirin group. One year after surgery, the patency rates of great saphenous vein bridge and internal mammary artery bridge were 94.5% (189/200) and 97.1% (66/68) in the indobuphen group, and 91.3% (189/207) and 96.9% (63/65) in the aspirin group, respectively. There was no significant difference in patency rate of great saphenous vein bridge and internal mammary artery bridge between the two groups (χ²=0.282, 0.345, P>0.05). The total incidence of adverse cardiac events was 5.4% (4/74) in the indobufen group and 6.7% (5/75) in the aspirin group (χ²=0.126, P>0.05). The overall incidence of gastrointestinal adverse reactions was significantly lower in the indobufen group than in the aspirin group (4.1% (3/74) vs. 13.3% (10/75), χ²=4.547, P<0.05). The levels of FIB, D-D, TM and TAFI in the two groups were lower than those before surgery (P<0.05), and there was no statistical significance between the two groups at baseline and post-operation (P>0.05). Conclusion: The efficacy of indobufen combined with clopidogrel in the prevention of 1-year restenosis after coronary artery bypass graft is similar to that of aspirin combined with clopidogrel, but the incidence of adverse reactions is lower, and the safety is higher in patients treated with indobufen combined with clopidogrel compared to aspirin combined with clopidogrel strategy.
Aspirin/therapeutic use*
;
Clopidogrel/therapeutic use*
;
Coronary Artery Bypass/adverse effects*
;
Drug Therapy, Combination
;
Humans
;
Isoindoles
;
Male
;
Phenylbutyrates
;
Platelet Aggregation Inhibitors/therapeutic use*
;
Prospective Studies
;
Treatment Outcome