BACKGROUND Metabolic-dysfunction associated steatotic liver disease(MASLD)is a hepatic manifestation of metabolic syndrome.Studies suggest ornithine aspartate(LOLA)as drug therapy.AIM To analyze the influence of LOLA ...BACKGROUND Metabolic-dysfunction associated steatotic liver disease(MASLD)is a hepatic manifestation of metabolic syndrome.Studies suggest ornithine aspartate(LOLA)as drug therapy.AIM To analyze the influence of LOLA intake on gut microbiota using a nutritional model of MASLD.METHODS Adult male Sprague Dawley rats were randomized into three groups:Control(10 rats fed with a standard diet),MASLD(10 rats fed with a high-fat and choline-deficient diet),and LOLA(10 rats receiving 200 mg/kg/d LOLA,after the 16th week receiving high-fat and choline-deficient diet).After 28 wk of the experiment,animals were euthanized,and feces present in the intestine were collected.Following fecal DNA extraction,the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™system.RESULTS Alpha and beta diversity metrics were comparable between MASLD and LOLA.3 OTUs were differentially abundant between MASLD and LOLA,which belong to the species Helicobacter rodentium,Parabacteroides goldsteinii,and Parabacteroides distasonis.The functional prediction provided two different metabolic profiles between MASLD and LOLA.The 9 pathways differentially abundant in MASLD are related to a change in energy source,adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides biosynthesis.The 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate,including tricarboxylic acid cycle pathways,purine/guanosine nucleotides biosynthesis,pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA biosynthesis.CONCLUSION Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLD,it was associated with changes in specific gut microbes and their related metabolic pathways.展开更多
C-14-glutamate and C-14-arginine were spreaded on leaves of six-day old barley (Hordeum vulgare L.) seedlings that were treated with NaCl 200 mmol/L. The result showed that the pathway of arginine-->ornithine-->...C-14-glutamate and C-14-arginine were spreaded on leaves of six-day old barley (Hordeum vulgare L.) seedlings that were treated with NaCl 200 mmol/L. The result showed that the pathway of arginine-->ornithine-->proline existed in the six-day old barley seedlings and was provoked remarkably by NaCl treatment. After seven days, proline accumulation contributed via the arginine-->ornithine-->proline pathway was 1.0 - 1.5 folds of that via the glutamate-->proline pathway. The activation of arginine-->ornithine-->proline pathway by salt stress in the salt-tolerant cultivar 'Jian 4' was 1.7 - 2.0 folds of that in the salt-sensitive cultivar 'KP 7', which suggested that the activation of arginine-->ornithine-->proline pathway in barley seedlings played an important role in improving salt tolerance of plants.展开更多
Ornithine transcarbamylase （OTC） deficiency is an X-linked trait that accounts for nearly half of all inherited disorders of the urea cycle. OTC is one of the enzymes common to both the urea cycle and the bacterial ...Ornithine transcarbamylase （OTC） deficiency is an X-linked trait that accounts for nearly half of all inherited disorders of the urea cycle. OTC is one of the enzymes common to both the urea cycle and the bacterial arginine biosynthesis pathway; however, the role of OTC has changed over evolution. For animals with a urea cycle, defects in OTC can trigger hyperammonemic episodes that can lead to brain damage and death. This is the fifth mutation update for human OTC with previous updates reported in 1993, 1995, 2002, and 2006. In the 2006 update, 341 mutations were reported. This current update contains 417 disease-causing mutations, and also is the first report of this series to incorporate information about natural variation of the OTC gene in the general population through examination of publicly available genomic data and examination of phenotype/genotype correlations from patients participating in the Urea Cycle Disorders Consortium Longitudinal Study and the first to evaluate the suitability of systematic computational approaches to predict severity of disease associated with different types of OTC mutations.展开更多
AIM: To investigate the expressions of omithine decarboxylase (ODC), MMP-2, and Erk, and their relationship in human colon tumors.METHODS: ODC activity, MMP-2 expression, and mitogenactivated protein (MAP) kinase acti...AIM: To investigate the expressions of omithine decarboxylase (ODC), MMP-2, and Erk, and their relationship in human colon tumors.METHODS: ODC activity, MMP-2 expression, and mitogenactivated protein (MAP) kinase activity (Erk phosphorylation) were determined in 58 surgically removed human colon tumors and their adjacent normal tissues, using [1-14C]-ornithine as a substrate, ELISA assay, and Western blotting, respectively.RESULTS: ODC activity, MMP-2 expression, and Erk phosphorylation were significantly elevated in colon tumors, compared to those in adjacent normal tissues. A significant correlation was observed between ODC activities and MMP-2 levels.CONCLUSION: This is the first report showing a significant correlation between ODC activities and MMP-2 levels in human colon tumors. As MMP-2 is involved in cancer invasion and metastasis, and colon cancer overexpresses ODC, suppression of ODC expression may be a rational approach to treat colon cancer which overexpresses ODC.展开更多
AIM: To investigate the expression of ornithine decarboxylase (ODC) in precancerous and cancerous gastric lesions. METHODS: We studied the expression of ODC in gastric mucosa from patients with chronic superficial gas...AIM: To investigate the expression of ornithine decarboxylase (ODC) in precancerous and cancerous gastric lesions. METHODS: We studied the expression of ODC in gastric mucosa from patients with chronic superficial gastritis (CSG,n = 32),chronic atrophic gastritis CAG,n = 43; 15 with and 28 without intestinal metaplasia (IM),gastric dysplasia (DYS,n = 11) and gastric cancer (GC,n = 48) tissues using immunohistochemical staining. All 134 biopsy specimens of gastric mucosa were collected by gastroscopy. METHODS: The positive rate of ODC expression was 34.4%,42.9%,73.3%,81.8% and 91.7% in cases with CSG,CAG without IM,CAG with IM,DYS and GC,respectively (P < 0.01),The positive rate of ODC expression increased in the order of CSG < CAG (without IM) < CAG (with IM) < DYS and finally,GC. In addition,ODC positive immunostaining rate was lower in well-differentiated GC than in poorly-differentiated GC (P < 0.05). CONCLUSION: The expression of ODC is positively correlated with the degree of malignity of gastric mucosa and development of gastric lesions. This finding indicates that ODC may be used as a good biomarker in the screening and diagnosis of precancerous lesions.展开更多
Ornithine transcarbamylase deficiency(OTCD) is an X-linked disorder,with an estimated prevalence of 1 per 80000 live births.Female patients with OTCD develop metabolic crises that are easily provoked by non-predictabl...Ornithine transcarbamylase deficiency(OTCD) is an X-linked disorder,with an estimated prevalence of 1 per 80000 live births.Female patients with OTCD develop metabolic crises that are easily provoked by non-predictable common disorders,such as genetic(private mutations and lyonization) and external factors;however,the outcomes of these conditions may differ.We resuscitated a female patient with OTCD from hyperammonemic crisis after she gave birth.Hyperammonemia after parturition in a female patient with OTCD can be fatal,and this type of hyperammonemia persists for an extended period of time.Here,we describe the cause and treatment of hyperammonemia in a female patient with OTCD after parturition.Once hyperammonemia crisis occurs after giving birth,it is difficult to improve the metabolic state.Therefore,it is important to perform an early intervention before hyperammonemia occurs in patients with OTCD or in carriers after parturition.展开更多
BACKGROUND Ornithine transcarbamylase deficiency(OTCD)is an X-linked inherited disorder and characterized by marked elevation of blood ammonia.The goal of treatment is to minimize the neurological damage caused by hyp...BACKGROUND Ornithine transcarbamylase deficiency(OTCD)is an X-linked inherited disorder and characterized by marked elevation of blood ammonia.The goal of treatment is to minimize the neurological damage caused by hyperammonemia.OTCD can be cured by liver transplantation(LT).Post-transplant patients can discontinue anti-hyperammonemia agents and consume a regular diet without the risk of developing hyperammonemia.The neurological damage caused by hyperammonemia is almost irreversible.CASE SUMMARY An 11.7-year-old boy presented with headache,vomiting,and altered consciousness.The patient was diagnosed with late-onset OTCD.After nitrogen scavenging treatment and a protein-free diet,ammonia levels were reduced to normal on the third day of admission.Nevertheless,the patient remained in a moderate coma.After discussion,LT was performed.Following LT,the patient’s blood ammonia and biochemical indicators stabilized in the normal range,he regained consciousness,and his nervous system function significantly recovered.Two months after LT,blood amino acids and urine organic acids were normal,and brain magnetic resonance imaging showed a decrease in subcortical lesions.CONCLUSION LT can significantly improve partial neurological impairment caused by late-onset OTCD hyperammonemic encephalopathy,and LT can be actively considered when early drug therapy is ineffective.展开更多
AIM To study the action of remedies of supporting resistance and relieving blood stasis on metastasis of postoperative gastric cancer and its influence on ornithine decarboxylase (ODC). METHODS Sixty three postope...AIM To study the action of remedies of supporting resistance and relieving blood stasis on metastasis of postoperative gastric cancer and its influence on ornithine decarboxylase (ODC). METHODS Sixty three postoperative gastric cancer patients were randomly divided into two groups. Thirty one patients were treated with western medicine consisting of the FAP scheme (5 flurouracil, adriamycin and cisplatin) and the CODP scheme (cyclophosphamide, vincristine, daunorubicin and prednisone), whereas 32 patients with the FAP scheme and traditional Chinese medicine. Correlations were approached between the ODC levels detected before and after treatment and some other factors including tumor diameter, infiltration depth, histological type and lymph node metastasis. RESULTS The ODC levels in the gastric cancers and normal gastric mucosa adjacent to the cancer tissues were significantly higher in the patients than those of the controls. The increasing ODC was obviously correlated with the tumor size, infiltration depth, differentiation type, and lymph node metastasis. Six months later there was no significant changes in the ODC levels of the group using only western medicine, while the ODC levels decreased markedly in the group using combined western and traditional Chinese medicine ( P <0 01). CONCLUSION The remedies of traditional Chinese medicine on the metastases of postoperative gastric cancers were related to the reduction of ODC activities.展开更多
Abnormally elevated activity of ornithine decarboxylase (ODC), and subsequent polyamine accumulation are intimately associated with the genesis.development and metastasis of cancer. In the present study, to control th...Abnormally elevated activity of ornithine decarboxylase (ODC), and subsequent polyamine accumulation are intimately associated with the genesis.development and metastasis of cancer. In the present study, to control the growth of tumor cells, ODC antisense RNA was used to transfect human lung squamous carcinoma cell line LTEP-78. Compared with the parental cells, growth of the antisense transfected LTEP-78 cells arrested in G0/Gl phase and colony formation in soft agarose and tumorigenicity in nude mice were significantly reduced. Nucleic acid hybridization demonstrated that the transfectants expressed a high level of ODC antisense RNA and a significantly reduced level of endogenous ODC mRNA.The results suggest that the reversion of malignant phenotypes of human lung squamous carcinoma cells transfected with ODC antisense RNA is associated with the inhibition of polyamine biosynthesis.展开更多
AIM: To investigate the ornithine decarboxylase (ODC)gene expression in colorectal carcinoma, ODC mRNA was assayed by RT-PCR and ODC protein was detected by a monoclonal antibody against fusion of human colon ODC prep...AIM: To investigate the ornithine decarboxylase (ODC)gene expression in colorectal carcinoma, ODC mRNA was assayed by RT-PCR and ODC protein was detected by a monoclonal antibody against fusion of human colon ODC prepared by hybridoma technology.METHODS: Total RNA was extracted from human colorectal cancer tissues and their normal counterpart tissues. ODC mRNA levels were examined by RT-PCR.ODC genes amplified from RT-PCR were cloned into a prokaryotic vector pQE-30. The expressed proteins were purified by chromatography. Anti-ODC mAb was prepared with classical hybridoma techniques and used to determine the ODC expression in colon cancer tissues by immunohistochemical and Western blotting assay.RESULTS: A cell line, which could steadily secrete antiODC mAb, was selected through subcloning four times.Western blotting reconfirmed the mAb and ELISA showed that its subtype was IgG2a. RT-PCR showed that the ODC mRNA level increased greatly in colon cancer tissues (P＜0.01). Immunohistochemical staining showed that colorectal carcinoma cells expressed a significantly higher level of ODC than normal colorectal mucosa (98.6±1.03%vs 5.26±5%, P＜0.01).CONCLUSION: ODC gene overexpression is significantly related to human colorectal carcinoma. ODC gene expression may be a marker for the gene diagnosis and therapy of colorectal carcinoma.展开更多
As a common urea-cycle disorder, ornithine transcarbamylase deficiency(OTCD) disables the conversion of ammonia into non-toxic urea, and its subsequent excretion results in hyperammonemia. We reported a 28-year-old wo...As a common urea-cycle disorder, ornithine transcarbamylase deficiency(OTCD) disables the conversion of ammonia into non-toxic urea, and its subsequent excretion results in hyperammonemia. We reported a 28-year-old woman who was diagnosed with OTCD during her first pregnancy. She was treated with arginine, citrulline and sodium benzoate for complications associated with hyperammonemia, and her protein intake was restricted. The patient’s condition was stabilized, and she delivered a baby boy via cesarean section. However, the baby died 2d later. During her second pregnancy, prenatal screening suggested that the fetus had OTCD, and an induced abortion was performed. During her third pregnancy, fetal OTCD was ruled out, and the patient was treated with oral sodium benzoate. Her blood ammonia level was stabilized, and a baby boy was successfully delivered via cesarean section. This case described the treatment process of the pregnant patient with OTCD, and the safety and efficacy of sodium benzoate were evaluated. Collectively, our findings provided the experience and evidence for the drug selection and treatment of these rare diseases.展开更多
BACKGROUND Ornithine transcarbamylase deficiency(OTCD)is a common ornithine cycle disorder,and OTC gene variation is the main pathogenic factor of this disease.This study explored and validated a variant in the OTC ge...BACKGROUND Ornithine transcarbamylase deficiency(OTCD)is a common ornithine cycle disorder,and OTC gene variation is the main pathogenic factor of this disease.This study explored and validated a variant in the OTC gene.CASE SUMMARY The neonate exhibited high blood ammonia,lactic acid,and homocysteine levels on the fifth day after birth.A novel deletion variant in the OTC gene[NM_000531.5,c.970_979delTTCCCAGAGG,p.Phe324GlnfsTer16]was uncovered by exome sequencing.The variant caused a protein-coding frameshift and resulted in early translation termination at the 16th amino acid after the variant site.CONCLUSION Our results provide a novel pathogenic variant in OTC and related clinical features for further OTCD screening and clinical consultation.展开更多
Curcumin the active component of turmeric is widely used as an anticancer agent for treating many human cancers. This study aimed at the extraction of curcumin from Curcuma Longa and investigates its therapeutic effec...Curcumin the active component of turmeric is widely used as an anticancer agent for treating many human cancers. This study aimed at the extraction of curcumin from Curcuma Longa and investigates its therapeutic effect as ornithine decarboxylase (ODC) inhibitor in HepG2 cells. The proliferation of HepG2 cells was carried out by using the MTT assay. In addition, cell cycle analysis was evaluated by using the flow-cytometric technique. Our results showed that curcumin has the ability to inhibit the proliferation of HepG2 cells with IC50 of 24.79 μg/ml and induced G2/M cell cycle arrest. Moreover, it caused an elevation in the intracellular concentration of Ca2+. Moreover, in the curcumin administration the downregulation expression level of ODC and Bcl-2 genes (p ≤ 0.05) was significant found. On the other hand, upregulation in the expression level of P53, Bax, and caspase-3 genes (p ≤ 0.05). This study concluded that curcumin may be considered as a new saving candidate for the future progress of antitumor agents.展开更多
The effect of oral L-ornithine hydrochloride (0.1 g/kg BW) on energy expenditure during a rest period from 120 to 180 min after resistance exercise was evaluated by indirect calorimetry. Healthy male subjects who have...The effect of oral L-ornithine hydrochloride (0.1 g/kg BW) on energy expenditure during a rest period from 120 to 180 min after resistance exercise was evaluated by indirect calorimetry. Healthy male subjects who have no habit of resistance training underwent resistance exercise (chest press, lat pulldown, leg press, shoulder press, leg extension, and leg curl), with 3 sets of each exercise and 10 repetitions in each set at 90-s intervals, 30 min after ingestion of ornithine or placebo. Plasma ornithine levels immediately after, and 120 and 180 min after, resistance exercise were significantly greater after ingestion of ornithine than of placebo (Treatment: F = 347.1, P p2 = 0.95;Interaction: F = 160.7, P p2 = 0.95), but no significant difference in serum growth hormone levels was observed between the two treatments (Treatment: F = 0.1, P = 0.751, ηp2 = 0.01;Time: F = 1.7, P = 0.229, ηp2 = 0.16;Interaction: F = 2.4, P = 0.155, ηp2 = 0.21). Although there was no between-treatment difference in energy expenditure during the rest period 120 to 180 min after resistance exercise (Treatment: F = 0.1, P = 0.718, ηp2 = 0.02;Time: F = 0.1, P = 0.767, ηp2 = 0.01;Interaction: F = 0.1, P = 0.112, ηp2 = 0.26), with ornithine ingestion carbohydrate oxidation was significantly greater than with placebo from 170 to 180 min after exercise (Treatment: F = 0.8, P = 0.383, ηp2 = 0.09;Time: F = 9.7, P = 0.013, ηp2 = 0.52;Interaction: F = 5.8, P = 0.039, ηp2 = 0.39). Moreover, 180 min after exercise, serum free fatty acid levels after ornithine ingestion were lower than after placebo (Treatment: F = 0.3, P = 0.602, ηp2 = 0.03;Time: F = 34.6, P p2 = 0.79;Interaction: F = 5.6, P = 0.042, ηp2 = 0.38). A similar trend in 3-hydroxybutylate was observed. In conclusion, ornithine ingestion before resistance exercise may enhance post-exercise carbohydrate oxidation without changing total energy expenditure.展开更多
DL-ornithine hydrochloride rods (3 ×10 mm) were studied to be a radiation sensitive material for EPR dosimetry. The rods have specified EPR signal developed under irradiation and its intensity increases with the ...DL-ornithine hydrochloride rods (3 ×10 mm) were studied to be a radiation sensitive material for EPR dosimetry. The rods have specified EPR signal developed under irradiation and its intensity increases with the increase in absorbed dose. The intensity also affected by the concentration of DL-ornithine in the rods. The prepared rods can be used in the dose range from 0.5 - 50 kGy. The obtained number of free radicals per 100 eV (G value) was found to be 0.3551 ± 0.0333. The hyperfine (hf) coupling constant is 2.325 mT at g-factor 2.033. The rods have the advantage of negligible humidity effects during irradiation. The pre and post- irradiation stability was found to be satisfactory.展开更多
32 postoperative cases of gastric carcinoma were treated by traditional Chinese medicine (TCM) drugs for supporting healthy energy and removing blood stasis, and their therapeutic results were compared with those in t...32 postoperative cases of gastric carcinoma were treated by traditional Chinese medicine (TCM) drugs for supporting healthy energy and removing blood stasis, and their therapeutic results were compared with those in the control group treated by western medicine. After 6 months of treatment, in the TCM group, the rate of metastatic recurrence was significantly reduced, and the level of ornithine decarboxylase was also markedly lowered. Therefore, it is considered that the action of anti-metastatic recurrence of TCM drugs in postoperative cases of gastric carcinoma is probably related to the lowered activity of ornithine decarboxylase.展开更多
Bi-directional translocation and degradation of Arginine (Arg) along the arbuscular mycorrhizal (AM) fungal mycelium were testified through 15N and/or 13C isotopic labeling. In vitro mycorrhizas of Glomus intraradices...Bi-directional translocation and degradation of Arginine (Arg) along the arbuscular mycorrhizal (AM) fungal mycelium were testified through 15N and/or 13C isotopic labeling. In vitro mycorrhizas of Glomus intraradices and Ri T-DNA-transformed carrot roots were grown in dual compartment Petri dishes. [15N- and/or13C]Arg was supplied to either the fungal compartment or the mycorrhizal compartment or separate dishes containing the uncolonized roots. The levels and labeling of free amino acids (AAs) in the mycorrhizal roots and in the extraradical mycelia(ERM) were measured by gas chromatogra- phy/mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC). The ERM of AM fungi exposed in either NH4+ or urea as sole external nitrogen source had much higher 15N enrichment of Arg, compared with those in nitrate or exogenous Arg; however, glycerol supplied as an external car- bon source to the ERM had no significant effect on the level of Arg in the ERM. Meanwhile, Arg bio- synthesized in the ERM could be translocated intact to the mycorrhizal roots and thereby the level of Arg in the mycorrhizal roots increased to about 20% after culture of ERM in 4 mmol/L NH4+ for 6 weeks. Also Arg was found to be bi-directionally transported along the AM fungal mycelium through [U-13C]Arg labeling either in the mycorrhizal compartment or in the fungal compartment. Once Arg was translo- cated to the potential N-limited sites, it would be further degraded into ornithine (Orn) and urea since either [U-13C] or [U-15N/U-13C]Orn was apparently shown up in the mycorrhizal root tissues when [U-13C] or [U-15N/U-13C]Arg was labeled in the fungal compartment, respectively. Evidently Orn formation indi- cated the ongoing activities of Arg translocation and degradation through the urea cycle in AM fungal mycelium.展开更多
Symbiotic fungi are involved in plant flooding tolerance,while the underlying mechanism is not yet known.Since polyamines(PAs)and proline are also associated with stress tolerance,it is hypothesized that the enhanceme...Symbiotic fungi are involved in plant flooding tolerance,while the underlying mechanism is not yet known.Since polyamines(PAs)and proline are also associated with stress tolerance,it is hypothesized that the enhancement of stress resistance by symbiotic fungi is associated with changes in PAs and/or proline.The aim of this study was to analyze the effect of inoculation with Funneliformis mosseae and Serendipita indica on plant growth,PAs,and proline and the metabolisms in peach(Prunus persica)under flooding.Two-week flooding did not affect root colonization frequence of F.mosseae,while it promoted root colonization frequence of S.indica.Under flooding,plants inoculated with F.mosseae and S.indica maintained relatively higher growth rates than uninoculated plants.Funneliformis mosseae promoted root ornithine(Orn)contentration and arginine(Arg)and Orn decarboxylase activities under flooding,which promoted putrescine(Put),cadaverine(Cad),and spermidine(Spd)contentrations.Conversely,S.indica decreased contentrations of Arg,Orn,and agmatine and Arg decarboxylase activities,thus decreasing PA contentrations under flooding.Polyamines were negatively correlated with the expression of PA uptake transporter genes,PpPUT1 and PpPUT2,in peach.Polyamine transporter genes of F.mosseae(FmTPO)and S.indica(SiTPO)were regulated by flooding,of which FmTPO1 was positively correlated with Put,Cad,and Spd,along with positive correlations of Spd with SiTPO1,SiTPO2,and SiTPO4.Under flooding,F.mosseae decreased proline concentration,while S.indica increased proline concentration and correlated with expression of a△^(1)-pyrroline-5-carboxylate synthetase gene,PpP5CS2.It was thus concluded that F.mosseae modulated polyamine accumulation,while S.indica induced proline accumulation to tolerate flooding.展开更多
During the investigation on transaminases of Schistosoma japonicum, we have observed that a considerable amount of glutamic acid was formed with arginine as substrate. Thereafter it was found that S. japonicum contain...During the investigation on transaminases of Schistosoma japonicum, we have observed that a considerable amount of glutamic acid was formed with arginine as substrate. Thereafter it was found that S. japonicum contained very active arginase; this led us to postulate that arginase展开更多
We report a case of double domino liver transplantation in a 32-year-old woman who was diagnosed with familial amyloid polyneuropathy(FAP) and liver dysfunction. A two-stage surgical plan was designed, and one domino ...We report a case of double domino liver transplantation in a 32-year-old woman who was diagnosed with familial amyloid polyneuropathy(FAP) and liver dysfunction. A two-stage surgical plan was designed, and one domino graft was implanted during each stage. During the firststage, an auxiliary domino liver transplantation was conducted using a domino graft from a 4-year-old female child with Wilson's disease. After removing the right lobe of the FAP patient's liver, the graft was rotated 90 degrees counterclockwise and placed along the right side of the inferior vena cava(IVC). The orifices of the left, middle, and right hepatic veins were reconstructed using an iliac vein patch and then anastomosed to the right side of the IVC. Thirty days later, a second domino liver graft was implanted. The second domino graft was from a 3-yearold female child with an ornithine carbamyl enzyme defect, and it replaced the residual native liver(left lobe). To balance the function and blood flow between the two grafts, a percutaneous transcatheter selective portal vein embolization was performed, and "the left portal vein" of the first graft was blocked 9 mo after the second transplantation. The liver function indices, blood ammonia, and 24-h urinary copper levels were normal at the end of a 3-year follow-up. These two domino donor grafts from donors with different metabolic disorders restored normal liver function. Our experience demonstrated a new approach for resolving metabolic disorders with domino grafts and utilizing explanted livers from children.展开更多
基金Financiamento e IncentivoàPesquisa from Hospital de Clínicas de Porto Alegre(FIPE/HCPA),No.2020-0037Coordination for the Improvement of Higher Education Personnel,CAPES/PNPDand the Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq).
文摘BACKGROUND Metabolic-dysfunction associated steatotic liver disease(MASLD)is a hepatic manifestation of metabolic syndrome.Studies suggest ornithine aspartate(LOLA)as drug therapy.AIM To analyze the influence of LOLA intake on gut microbiota using a nutritional model of MASLD.METHODS Adult male Sprague Dawley rats were randomized into three groups:Control(10 rats fed with a standard diet),MASLD(10 rats fed with a high-fat and choline-deficient diet),and LOLA(10 rats receiving 200 mg/kg/d LOLA,after the 16th week receiving high-fat and choline-deficient diet).After 28 wk of the experiment,animals were euthanized,and feces present in the intestine were collected.Following fecal DNA extraction,the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™system.RESULTS Alpha and beta diversity metrics were comparable between MASLD and LOLA.3 OTUs were differentially abundant between MASLD and LOLA,which belong to the species Helicobacter rodentium,Parabacteroides goldsteinii,and Parabacteroides distasonis.The functional prediction provided two different metabolic profiles between MASLD and LOLA.The 9 pathways differentially abundant in MASLD are related to a change in energy source,adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides biosynthesis.The 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate,including tricarboxylic acid cycle pathways,purine/guanosine nucleotides biosynthesis,pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA biosynthesis.CONCLUSION Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLD,it was associated with changes in specific gut microbes and their related metabolic pathways.
文摘C-14-glutamate and C-14-arginine were spreaded on leaves of six-day old barley (Hordeum vulgare L.) seedlings that were treated with NaCl 200 mmol/L. The result showed that the pathway of arginine-->ornithine-->proline existed in the six-day old barley seedlings and was provoked remarkably by NaCl treatment. After seven days, proline accumulation contributed via the arginine-->ornithine-->proline pathway was 1.0 - 1.5 folds of that via the glutamate-->proline pathway. The activation of arginine-->ornithine-->proline pathway by salt stress in the salt-tolerant cultivar 'Jian 4' was 1.7 - 2.0 folds of that in the salt-sensitive cultivar 'KP 7', which suggested that the activation of arginine-->ornithine-->proline pathway in barley seedlings played an important role in improving salt tolerance of plants.
基金the support of the Kettering Family FoundationThe Urea Cycle Disorders Consortium (U54HD061221) is a part of the National Institutes of Health (NIH) Rare Disease Clinical Research Network (RDCRN)+3 种基金supported through collaboration between the Office of Rare Diseases Research (ORDR)the National Center for Advancing Translational Science (NCATS)the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)The Urea Cycle Disorders Consortium is also supported by the O’Malley Foundation, the Rotenberg Family Fund, the Dietmar-Hopp Foundation, and the Kettering Fund
文摘Ornithine transcarbamylase （OTC） deficiency is an X-linked trait that accounts for nearly half of all inherited disorders of the urea cycle. OTC is one of the enzymes common to both the urea cycle and the bacterial arginine biosynthesis pathway; however, the role of OTC has changed over evolution. For animals with a urea cycle, defects in OTC can trigger hyperammonemic episodes that can lead to brain damage and death. This is the fifth mutation update for human OTC with previous updates reported in 1993, 1995, 2002, and 2006. In the 2006 update, 341 mutations were reported. This current update contains 417 disease-causing mutations, and also is the first report of this series to incorporate information about natural variation of the OTC gene in the general population through examination of publicly available genomic data and examination of phenotype/genotype correlations from patients participating in the Urea Cycle Disorders Consortium Longitudinal Study and the first to evaluate the suitability of systematic computational approaches to predict severity of disease associated with different types of OTC mutations.
基金Supported by a Grant Under the Ministry of Education, Science,Sports, and Culture, Japan
文摘AIM: To investigate the expressions of omithine decarboxylase (ODC), MMP-2, and Erk, and their relationship in human colon tumors.METHODS: ODC activity, MMP-2 expression, and mitogenactivated protein (MAP) kinase activity (Erk phosphorylation) were determined in 58 surgically removed human colon tumors and their adjacent normal tissues, using [1-14C]-ornithine as a substrate, ELISA assay, and Western blotting, respectively.RESULTS: ODC activity, MMP-2 expression, and Erk phosphorylation were significantly elevated in colon tumors, compared to those in adjacent normal tissues. A significant correlation was observed between ODC activities and MMP-2 levels.CONCLUSION: This is the first report showing a significant correlation between ODC activities and MMP-2 levels in human colon tumors. As MMP-2 is involved in cancer invasion and metastasis, and colon cancer overexpresses ODC, suppression of ODC expression may be a rational approach to treat colon cancer which overexpresses ODC.
基金Supported by Miao Pu Foundation of Hainan Medical College, No. 2004108Natural Science Foundation of Hainan Province, No. 80582
文摘AIM: To investigate the expression of ornithine decarboxylase (ODC) in precancerous and cancerous gastric lesions. METHODS: We studied the expression of ODC in gastric mucosa from patients with chronic superficial gastritis (CSG,n = 32),chronic atrophic gastritis CAG,n = 43; 15 with and 28 without intestinal metaplasia (IM),gastric dysplasia (DYS,n = 11) and gastric cancer (GC,n = 48) tissues using immunohistochemical staining. All 134 biopsy specimens of gastric mucosa were collected by gastroscopy. METHODS: The positive rate of ODC expression was 34.4%,42.9%,73.3%,81.8% and 91.7% in cases with CSG,CAG without IM,CAG with IM,DYS and GC,respectively (P < 0.01),The positive rate of ODC expression increased in the order of CSG < CAG (without IM) < CAG (with IM) < DYS and finally,GC. In addition,ODC positive immunostaining rate was lower in well-differentiated GC than in poorly-differentiated GC (P < 0.05). CONCLUSION: The expression of ODC is positively correlated with the degree of malignity of gastric mucosa and development of gastric lesions. This finding indicates that ODC may be used as a good biomarker in the screening and diagnosis of precancerous lesions.
基金Supported by A Grant-in-Aid for Guidelines and Lifetime Medical Support Systems for inborn errors of metabolism found by newborn screeninga Grant-in-Aid for the Practical Research Project for Rare/Intractable Diseases from Japan Agency for Medical Research and Development,AMED
文摘Ornithine transcarbamylase deficiency(OTCD) is an X-linked disorder,with an estimated prevalence of 1 per 80000 live births.Female patients with OTCD develop metabolic crises that are easily provoked by non-predictable common disorders,such as genetic(private mutations and lyonization) and external factors;however,the outcomes of these conditions may differ.We resuscitated a female patient with OTCD from hyperammonemic crisis after she gave birth.Hyperammonemia after parturition in a female patient with OTCD can be fatal,and this type of hyperammonemia persists for an extended period of time.Here,we describe the cause and treatment of hyperammonemia in a female patient with OTCD after parturition.Once hyperammonemia crisis occurs after giving birth,it is difficult to improve the metabolic state.Therefore,it is important to perform an early intervention before hyperammonemia occurs in patients with OTCD or in carriers after parturition.
基金Supported by the Sanming Project of Medicine in Shenzhen,No.SZSM201812005。
文摘BACKGROUND Ornithine transcarbamylase deficiency(OTCD)is an X-linked inherited disorder and characterized by marked elevation of blood ammonia.The goal of treatment is to minimize the neurological damage caused by hyperammonemia.OTCD can be cured by liver transplantation(LT).Post-transplant patients can discontinue anti-hyperammonemia agents and consume a regular diet without the risk of developing hyperammonemia.The neurological damage caused by hyperammonemia is almost irreversible.CASE SUMMARY An 11.7-year-old boy presented with headache,vomiting,and altered consciousness.The patient was diagnosed with late-onset OTCD.After nitrogen scavenging treatment and a protein-free diet,ammonia levels were reduced to normal on the third day of admission.Nevertheless,the patient remained in a moderate coma.After discussion,LT was performed.Following LT,the patient’s blood ammonia and biochemical indicators stabilized in the normal range,he regained consciousness,and his nervous system function significantly recovered.Two months after LT,blood amino acids and urine organic acids were normal,and brain magnetic resonance imaging showed a decrease in subcortical lesions.CONCLUSION LT can significantly improve partial neurological impairment caused by late-onset OTCD hyperammonemic encephalopathy,and LT can be actively considered when early drug therapy is ineffective.
文摘AIM To study the action of remedies of supporting resistance and relieving blood stasis on metastasis of postoperative gastric cancer and its influence on ornithine decarboxylase (ODC). METHODS Sixty three postoperative gastric cancer patients were randomly divided into two groups. Thirty one patients were treated with western medicine consisting of the FAP scheme (5 flurouracil, adriamycin and cisplatin) and the CODP scheme (cyclophosphamide, vincristine, daunorubicin and prednisone), whereas 32 patients with the FAP scheme and traditional Chinese medicine. Correlations were approached between the ODC levels detected before and after treatment and some other factors including tumor diameter, infiltration depth, histological type and lymph node metastasis. RESULTS The ODC levels in the gastric cancers and normal gastric mucosa adjacent to the cancer tissues were significantly higher in the patients than those of the controls. The increasing ODC was obviously correlated with the tumor size, infiltration depth, differentiation type, and lymph node metastasis. Six months later there was no significant changes in the ODC levels of the group using only western medicine, while the ODC levels decreased markedly in the group using combined western and traditional Chinese medicine ( P <0 01). CONCLUSION The remedies of traditional Chinese medicine on the metastases of postoperative gastric cancers were related to the reduction of ODC activities.
文摘Abnormally elevated activity of ornithine decarboxylase (ODC), and subsequent polyamine accumulation are intimately associated with the genesis.development and metastasis of cancer. In the present study, to control the growth of tumor cells, ODC antisense RNA was used to transfect human lung squamous carcinoma cell line LTEP-78. Compared with the parental cells, growth of the antisense transfected LTEP-78 cells arrested in G0/Gl phase and colony formation in soft agarose and tumorigenicity in nude mice were significantly reduced. Nucleic acid hybridization demonstrated that the transfectants expressed a high level of ODC antisense RNA and a significantly reduced level of endogenous ODC mRNA.The results suggest that the reversion of malignant phenotypes of human lung squamous carcinoma cells transfected with ODC antisense RNA is associated with the inhibition of polyamine biosynthesis.
基金Supported by the Scientific Research Fund of National Ministry of Health, No. 98-1-173
文摘AIM: To investigate the ornithine decarboxylase (ODC)gene expression in colorectal carcinoma, ODC mRNA was assayed by RT-PCR and ODC protein was detected by a monoclonal antibody against fusion of human colon ODC prepared by hybridoma technology.METHODS: Total RNA was extracted from human colorectal cancer tissues and their normal counterpart tissues. ODC mRNA levels were examined by RT-PCR.ODC genes amplified from RT-PCR were cloned into a prokaryotic vector pQE-30. The expressed proteins were purified by chromatography. Anti-ODC mAb was prepared with classical hybridoma techniques and used to determine the ODC expression in colon cancer tissues by immunohistochemical and Western blotting assay.RESULTS: A cell line, which could steadily secrete antiODC mAb, was selected through subcloning four times.Western blotting reconfirmed the mAb and ELISA showed that its subtype was IgG2a. RT-PCR showed that the ODC mRNA level increased greatly in colon cancer tissues (P＜0.01). Immunohistochemical staining showed that colorectal carcinoma cells expressed a significantly higher level of ODC than normal colorectal mucosa (98.6±1.03%vs 5.26±5%, P＜0.01).CONCLUSION: ODC gene overexpression is significantly related to human colorectal carcinoma. ODC gene expression may be a marker for the gene diagnosis and therapy of colorectal carcinoma.
基金Clinical Trial of Xinhua Hospital(Grant No.15LC11)。
文摘As a common urea-cycle disorder, ornithine transcarbamylase deficiency(OTCD) disables the conversion of ammonia into non-toxic urea, and its subsequent excretion results in hyperammonemia. We reported a 28-year-old woman who was diagnosed with OTCD during her first pregnancy. She was treated with arginine, citrulline and sodium benzoate for complications associated with hyperammonemia, and her protein intake was restricted. The patient’s condition was stabilized, and she delivered a baby boy via cesarean section. However, the baby died 2d later. During her second pregnancy, prenatal screening suggested that the fetus had OTCD, and an induced abortion was performed. During her third pregnancy, fetal OTCD was ruled out, and the patient was treated with oral sodium benzoate. Her blood ammonia level was stabilized, and a baby boy was successfully delivered via cesarean section. This case described the treatment process of the pregnant patient with OTCD, and the safety and efficacy of sodium benzoate were evaluated. Collectively, our findings provided the experience and evidence for the drug selection and treatment of these rare diseases.
文摘BACKGROUND Ornithine transcarbamylase deficiency(OTCD)is a common ornithine cycle disorder,and OTC gene variation is the main pathogenic factor of this disease.This study explored and validated a variant in the OTC gene.CASE SUMMARY The neonate exhibited high blood ammonia,lactic acid,and homocysteine levels on the fifth day after birth.A novel deletion variant in the OTC gene[NM_000531.5,c.970_979delTTCCCAGAGG,p.Phe324GlnfsTer16]was uncovered by exome sequencing.The variant caused a protein-coding frameshift and resulted in early translation termination at the 16th amino acid after the variant site.CONCLUSION Our results provide a novel pathogenic variant in OTC and related clinical features for further OTCD screening and clinical consultation.
文摘Curcumin the active component of turmeric is widely used as an anticancer agent for treating many human cancers. This study aimed at the extraction of curcumin from Curcuma Longa and investigates its therapeutic effect as ornithine decarboxylase (ODC) inhibitor in HepG2 cells. The proliferation of HepG2 cells was carried out by using the MTT assay. In addition, cell cycle analysis was evaluated by using the flow-cytometric technique. Our results showed that curcumin has the ability to inhibit the proliferation of HepG2 cells with IC50 of 24.79 μg/ml and induced G2/M cell cycle arrest. Moreover, it caused an elevation in the intracellular concentration of Ca2+. Moreover, in the curcumin administration the downregulation expression level of ODC and Bcl-2 genes (p ≤ 0.05) was significant found. On the other hand, upregulation in the expression level of P53, Bax, and caspase-3 genes (p ≤ 0.05). This study concluded that curcumin may be considered as a new saving candidate for the future progress of antitumor agents.
文摘The effect of oral L-ornithine hydrochloride (0.1 g/kg BW) on energy expenditure during a rest period from 120 to 180 min after resistance exercise was evaluated by indirect calorimetry. Healthy male subjects who have no habit of resistance training underwent resistance exercise (chest press, lat pulldown, leg press, shoulder press, leg extension, and leg curl), with 3 sets of each exercise and 10 repetitions in each set at 90-s intervals, 30 min after ingestion of ornithine or placebo. Plasma ornithine levels immediately after, and 120 and 180 min after, resistance exercise were significantly greater after ingestion of ornithine than of placebo (Treatment: F = 347.1, P p2 = 0.95;Interaction: F = 160.7, P p2 = 0.95), but no significant difference in serum growth hormone levels was observed between the two treatments (Treatment: F = 0.1, P = 0.751, ηp2 = 0.01;Time: F = 1.7, P = 0.229, ηp2 = 0.16;Interaction: F = 2.4, P = 0.155, ηp2 = 0.21). Although there was no between-treatment difference in energy expenditure during the rest period 120 to 180 min after resistance exercise (Treatment: F = 0.1, P = 0.718, ηp2 = 0.02;Time: F = 0.1, P = 0.767, ηp2 = 0.01;Interaction: F = 0.1, P = 0.112, ηp2 = 0.26), with ornithine ingestion carbohydrate oxidation was significantly greater than with placebo from 170 to 180 min after exercise (Treatment: F = 0.8, P = 0.383, ηp2 = 0.09;Time: F = 9.7, P = 0.013, ηp2 = 0.52;Interaction: F = 5.8, P = 0.039, ηp2 = 0.39). Moreover, 180 min after exercise, serum free fatty acid levels after ornithine ingestion were lower than after placebo (Treatment: F = 0.3, P = 0.602, ηp2 = 0.03;Time: F = 34.6, P p2 = 0.79;Interaction: F = 5.6, P = 0.042, ηp2 = 0.38). A similar trend in 3-hydroxybutylate was observed. In conclusion, ornithine ingestion before resistance exercise may enhance post-exercise carbohydrate oxidation without changing total energy expenditure.
文摘DL-ornithine hydrochloride rods (3 ×10 mm) were studied to be a radiation sensitive material for EPR dosimetry. The rods have specified EPR signal developed under irradiation and its intensity increases with the increase in absorbed dose. The intensity also affected by the concentration of DL-ornithine in the rods. The prepared rods can be used in the dose range from 0.5 - 50 kGy. The obtained number of free radicals per 100 eV (G value) was found to be 0.3551 ± 0.0333. The hyperfine (hf) coupling constant is 2.325 mT at g-factor 2.033. The rods have the advantage of negligible humidity effects during irradiation. The pre and post- irradiation stability was found to be satisfactory.
文摘32 postoperative cases of gastric carcinoma were treated by traditional Chinese medicine (TCM) drugs for supporting healthy energy and removing blood stasis, and their therapeutic results were compared with those in the control group treated by western medicine. After 6 months of treatment, in the TCM group, the rate of metastatic recurrence was significantly reduced, and the level of ornithine decarboxylase was also markedly lowered. Therefore, it is considered that the action of anti-metastatic recurrence of TCM drugs in postoperative cases of gastric carcinoma is probably related to the lowered activity of ornithine decarboxylase.
基金Supported by Science and Technology Department of Zhejiang Province (Grant No. 2006C22009).
文摘Bi-directional translocation and degradation of Arginine (Arg) along the arbuscular mycorrhizal (AM) fungal mycelium were testified through 15N and/or 13C isotopic labeling. In vitro mycorrhizas of Glomus intraradices and Ri T-DNA-transformed carrot roots were grown in dual compartment Petri dishes. [15N- and/or13C]Arg was supplied to either the fungal compartment or the mycorrhizal compartment or separate dishes containing the uncolonized roots. The levels and labeling of free amino acids (AAs) in the mycorrhizal roots and in the extraradical mycelia(ERM) were measured by gas chromatogra- phy/mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC). The ERM of AM fungi exposed in either NH4+ or urea as sole external nitrogen source had much higher 15N enrichment of Arg, compared with those in nitrate or exogenous Arg; however, glycerol supplied as an external car- bon source to the ERM had no significant effect on the level of Arg in the ERM. Meanwhile, Arg bio- synthesized in the ERM could be translocated intact to the mycorrhizal roots and thereby the level of Arg in the mycorrhizal roots increased to about 20% after culture of ERM in 4 mmol/L NH4+ for 6 weeks. Also Arg was found to be bi-directionally transported along the AM fungal mycelium through [U-13C]Arg labeling either in the mycorrhizal compartment or in the fungal compartment. Once Arg was translo- cated to the potential N-limited sites, it would be further degraded into ornithine (Orn) and urea since either [U-13C] or [U-15N/U-13C]Orn was apparently shown up in the mycorrhizal root tissues when [U-13C] or [U-15N/U-13C]Arg was labeled in the fungal compartment, respectively. Evidently Orn formation indi- cated the ongoing activities of Arg translocation and degradation through the urea cycle in AM fungal mycelium.
基金supported by the Open Fund of Engineering Research Center of Ecology and Agricultural Use of Wetland,Ministry of Education,China(No.KFT202005)。
文摘Symbiotic fungi are involved in plant flooding tolerance,while the underlying mechanism is not yet known.Since polyamines(PAs)and proline are also associated with stress tolerance,it is hypothesized that the enhancement of stress resistance by symbiotic fungi is associated with changes in PAs and/or proline.The aim of this study was to analyze the effect of inoculation with Funneliformis mosseae and Serendipita indica on plant growth,PAs,and proline and the metabolisms in peach(Prunus persica)under flooding.Two-week flooding did not affect root colonization frequence of F.mosseae,while it promoted root colonization frequence of S.indica.Under flooding,plants inoculated with F.mosseae and S.indica maintained relatively higher growth rates than uninoculated plants.Funneliformis mosseae promoted root ornithine(Orn)contentration and arginine(Arg)and Orn decarboxylase activities under flooding,which promoted putrescine(Put),cadaverine(Cad),and spermidine(Spd)contentrations.Conversely,S.indica decreased contentrations of Arg,Orn,and agmatine and Arg decarboxylase activities,thus decreasing PA contentrations under flooding.Polyamines were negatively correlated with the expression of PA uptake transporter genes,PpPUT1 and PpPUT2,in peach.Polyamine transporter genes of F.mosseae(FmTPO)and S.indica(SiTPO)were regulated by flooding,of which FmTPO1 was positively correlated with Put,Cad,and Spd,along with positive correlations of Spd with SiTPO1,SiTPO2,and SiTPO4.Under flooding,F.mosseae decreased proline concentration,while S.indica increased proline concentration and correlated with expression of a△^(1)-pyrroline-5-carboxylate synthetase gene,PpP5CS2.It was thus concluded that F.mosseae modulated polyamine accumulation,while S.indica induced proline accumulation to tolerate flooding.
文摘During the investigation on transaminases of Schistosoma japonicum, we have observed that a considerable amount of glutamic acid was formed with arginine as substrate. Thereafter it was found that S. japonicum contained very active arginase; this led us to postulate that arginase
基金Supported by Capital Special Program for Health Research and Development,No.2016-1-2021National Key Technologies R&D Program,No.2015BAI13B09+1 种基金The Training Program of Academic Leaders in Beijing Health System,No.2014-2-002Beijing Municipal Administration of Hospitals Ascent Plan,No.DFL20150101
文摘We report a case of double domino liver transplantation in a 32-year-old woman who was diagnosed with familial amyloid polyneuropathy(FAP) and liver dysfunction. A two-stage surgical plan was designed, and one domino graft was implanted during each stage. During the firststage, an auxiliary domino liver transplantation was conducted using a domino graft from a 4-year-old female child with Wilson's disease. After removing the right lobe of the FAP patient's liver, the graft was rotated 90 degrees counterclockwise and placed along the right side of the inferior vena cava(IVC). The orifices of the left, middle, and right hepatic veins were reconstructed using an iliac vein patch and then anastomosed to the right side of the IVC. Thirty days later, a second domino liver graft was implanted. The second domino graft was from a 3-yearold female child with an ornithine carbamyl enzyme defect, and it replaced the residual native liver(left lobe). To balance the function and blood flow between the two grafts, a percutaneous transcatheter selective portal vein embolization was performed, and "the left portal vein" of the first graft was blocked 9 mo after the second transplantation. The liver function indices, blood ammonia, and 24-h urinary copper levels were normal at the end of a 3-year follow-up. These two domino donor grafts from donors with different metabolic disorders restored normal liver function. Our experience demonstrated a new approach for resolving metabolic disorders with domino grafts and utilizing explanted livers from children.
