Ornithine aspartate effects on bacterial composition and metabolic pathways in a rat model of steatotic liver disease

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.

Ornithine Pathway in Proline Biosynthesis Activated by Salt Stress in Barley Seedlings

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.

Ornithine decarboxylase, mitogen-activated protein kinase and matrix metalloproteinase-2 expressions in human colon tumors

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.

Expression of ornithine decarboxylase in precancerous and cancerous gastric lesions

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.

Effect of remedies of supporting resistance and relieving blood stasis on metastasis of postoperative gastric cancer and ornithine decarboxylase

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.

REVERSION OF MALIGNANT PHENOTYPES OF HUMAN LUNG SQUAMOUS CARCINOMA CELLS BY ORNITHINE DECARBOXYLASE ANTISENSE RNA

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.

Hyperammonemia crisis following parturition in a female patient with ornithine transcarbamylase deficiency

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.

Liver transplantation for late-onset ornithine transcarbamylase deficiency:A case report

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.

Ornithine decarboxylase gene is overexpressed in colorectal carcinoma

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.

The effect of L-ornithine hydrochloride ingestion on human growth hormone secretion after strength training

This study aimed to examine the effect of L-ornithine hydrochloride ingestion on serum growth hormone secretion response after strength training in young men who did not regularly engage in high intensity exercise. Ten healthy young males without workout habits (age: 22.2 +/- 1.0 yr). Subjects performed biceps curl strength training after L-ornithine hydro- chloride and placebo ingestions. They participated in both of the above conditions randomly with a week interval in between. Serum growth hormone and ornithine levels were measured before L-ornithine hydrochloride or placebo ingestions and at 30 minutes after strength training. Serum growth hormone and ornithine level were measured. A change magnitude of serum growth hormone was significantly larger in the L-ornithine hydrochloride condition than in the placebo condition, and the effect size was also large (t = 1.91, p = .044, ES = .75). A significant interaction (F = 280.98, p = 0.000, ηp2 = 0.96) was found in serum ornithine and a multiple comparison test showed that it was greater in the L-ornithine hydrochloride condition. Serum growth hormone level after strength training increases by L-ornithine hydrochloride ingestion in untrained young males.

The Inhibitory Effect of Curcumin on Ornithine Decarboxylase against Hepatic Carcinoma

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.

Hemizygous deletion in the OTC gene results in ornithine transcarbamylase deficiency:A case report

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.

The effect of ornithine ingestion on carbohydrate metabolism during rest after acute resistance exercise in healthy young males

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.

L-ornithine hydrochloride ingestion increased carbohydrate oxidation but not lipid oxidation during submaximal endurance exercise following resistance exercise

This study aimed to examine the effect of L-ornithine hydrochloride ingestion on lipid oxidation during submaximal endurance exercise following resistance exercise. Ten healthy young male adults with no history of regular resistance exercise (age: 26.0 +/- 4.4) conducted resistance exercise after L-ornithine hydrochloride or placebo ingestion (0.1 g/kg). Subjects exercised for 60 min on an ergometer at 50% VO2peak 120 min after resistance exercise. Plasma ornithine concentrations measured immediately, 120min and 180min after resistance exercise in the L-ornithine hydrochloride ingestion condition were significantly greater than those in the placebo condition. No significant difference was found in serum growth hor mone concentrations between both conditions (F = 4.4, p = 0.065). Serum free fatty acid concentrations were significantly greater immediately after submaximal ergometer bicycle exercise in both conditions than those before ingestion, immediately after resistance exercise and 120min after resistance exercise (F = 43.4, p .001, 300% - 508%), but no significant difference was found between both conditions (F = 3.6, p = 0.090). A similar trend was observed in serum ketone bodies as well. Although total energy production during submaximal ergometer exercise did not significantly differ (t = 0.74, p = 0.238), a significant difference was found in energy production via carbohydrate and lipid oxidation;the former was greater in the Lornithine hydrochloride ingestion condition (t = 1.89, p = 0.046, d = 0.44, 106%), and the latter was greater in the placebo condition (t = 1.89, p = 0.046, d = 0.78%, 145%). From the above, L-ornithine hydrochloride ingestion may not affect lipid metabolism during submaximal endurance exercise following resistance exercise. It may be involved in energy production via carbohydrate oxidation with glucogenic amino acid.

ESR Dosimetric Study on Gamma Induced Radicals in DL-Ornithine Hydrochloride

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.

THE EFFECTS OF CHINESE DRUGS FOR SUPPORTING HEALTHY ENERGY AND REMOVING BLOOD STASIS ON POSTOPERATIVE METASTASIS OF GASTRIC CARCINOMA AND ORNITHINE DECARBOXYLASE

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.

Genotype-Phenotype Correlations in Ornithine Transcarbamylase Deficiency: A Mutation Update

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.

苯丁酸甘油酯治疗儿童鸟氨酸氨甲酰基转移酶缺乏症1例

苯丁酸甘油酯(glyceryl phenylbutyrate,GPB)是治疗鸟氨酸氨甲酰基转移酶缺乏症(ornithine transcarbamylase deficiency,OTCD)的长期管理药物,可有效控制高氨血症,但国内使用该药的经验匮乏。该文回顾性分析上海交通大学医学院附属上海儿童医学中心1例诊断为OTCD的患儿资料,并进行相关文献复习。该患儿确诊后使用GPB治疗,随后进行疗效随访和药学监测。患儿,男,6岁6个月,语言发育差,不听指令,脾气暴躁并伴有攻击性行为。监测血氨最高327μmol/L;尿有机酸分析提示尿嘧啶水平升高;头颅磁共振成像示双侧大脑半球广泛异常信号;基因检测发现OTC基因新生突变(c.241T>C,p.S81P)。予以GPB治疗后1、2、3个月左右的血氨分别为43、80、56μmol/L。患儿治疗期间血氨控制良好,未见与药物相关的不良反应,发育落后情况较前改善,可听指令,脾气好转,无攻击性行为。

以鸟氨酸循环为例探讨生物化学课程教学方法及思政融入

生物化学课程的代谢内容涉及很多循环代谢,占据生物化学课程代谢的半壁江山,且多为难点和重点。为了达到较好的教学效果,文章以鸟氨酸循环为例,采用多种教学手段和技巧积极探索和尝试,旨在达到学生掌握知识的同时,学会掌握代谢的逻辑,提高学习能力,提升科研思维。同时融入恰当的思政内容,以期提高生物化学课程的教学质量。

迟发性鸟氨酸氨甲酰转移酶缺乏症1例的OTC基因变异分析

目的:对1例迟发型鸟氨酸氨甲酰转移酶缺乏症(OTCD)患儿的临床特点及OTC基因变异进行分析,提高对鸟氨酸氨甲酰转移酶缺乏症的认识。方法:对2023年2月20日本院收治的1例OTCD患儿及父母外周血样,采用高通量测序的方法进行全外显子测序(WES),对候选致病变异进行Sanger测序验证及生物信息学分析变异蛋白结构。结果:患儿OTC基因第4外显子存在c.356G>A(p.Gly119Asp)变异。根据美国医学遗传学与基因组学学会变异相关指南,判定为可能致病性变异(PM1+PM2_Supporting+PP3_Strong),在多个正常人群数据库的频率为0,采用Sanger测序技术对先证者及其父母OTC基因变异验证。先证者的变异经一代测序技术证实,生母携带此杂合变异。结论:OTC基因变异可能是此例迟发型OTCD患儿的遗传学病因。c.356G>A的发现丰富了OTC基因的变异谱。提示基因检测在代谢疾病中的重要性。