Glutamine Transaminase Research Articles

A case-series study of hepatic left lateral segment inversion for surgical field exposure in laparoscopic gastrectomy

PurposeRetraction of the hepatic left lateral segment (HLLS) is a crucial maneuver for surgical field exposure during laparoscopic gastrectomy with systematic lymphadenectomy. Though various methods of retraction are available, there is no perfect solution. Here, we report the results of our initial 42 cases with HLLS inversion method and discuss the feasibility, safety, effectiveness and technical aspects of this method.MethodsThe intraoperative and postoperative short-term outcomes of 42 patients who underwent HLLS inversion during laparoscopic total gastrectomy and proximal gastrectomy in our department September, 2023 to January, 2024 were reviewed. HLLS inversion was performed by mobilizing the HLLS and inverting it to the right supra-hepatic space through an incision at the falciform ligament.Results42 patients underwent HLLS inversion successfully with an average time of 13.9 min. 7 patients needed re-inversion due to slipping back of the HLLS during operation. Optimal exposure of the surgical field was achieved in all patients. No intra-operative complications occurred, except for 1 patient presented with mild intraoperative hepatic hemorrhage requiring electrocoagulation for hemostasis. Alanine aminotransferase and glutamine aminotransferase elevated in some patients on postoperative day 1(POD1), but declined to preoperative levels on the 7th postoperative day. There were no Clavien-Dindo II grade or higher digestive complications after surgery. In 5 patients with preservation the hepatic branch of the vagus nerve, the contractile function of the gall bladder was intact or slightly impaired 2 weeks after operation.ConclusionFor laparoscopic proximal gastrectomy (LPG) and laparoscopic total gastrectomy (LTG), HLLS inversion is a feasible method for optimizing visualization of the surgical field with preservation of the function of the hepatic branch of the vagus nerve. It is safe and acceptable as to the manipulation time. Re-inversion is easy and effective even in case of failure of inversion. HLLS inversion seems to be a promising technique for retraction of the liver during laparoscopic gastrectomy.

Encapsulation of roast beef flavor by soy protein isolate/chitosan complex Pickering emulsions to improve its releasing properties during the processing of plant-based meat analogues

During the production of plant-based meat analogues (PBMA), a significant loss of flavor characteristic compounds in meat-flavor essences could be observed. Pickering emulsion-based encapsulation is an effective method to improve their stability. Therefore, a soy protein isolate (SPI)/chitosan (CS) complex Pickering emulsion was fabricated to encapsulate roast beef flavor (RBF) and further applied in the processing of PBMA. Our results indicated that the network structure of emulsions was dominated by elasticity, while hydrogen and covalent bonding interactions played important roles in the encapsulation process. The release rate of flavor compounds gradually increased with the increase of pH value, glutamine transaminase, NaCl content, heating temperature or heating time, while encapsulation significantly reduced the loss of characteristic aroma compounds. In addition, the releasing characteristics of aroma compounds and textural properties of PBMA were greatly improved by treating with RBF-loaded emulsions. Consequently, the emulsions were promising to improve the flavor quality of PBMA.

Energy Metabolites and Indicative Significance of α-Ketoglutarate and α-Ketoglutaramate in Assessing the Progression of Chronic Hepatoencephalopathy.

In the example of a rat model with chronic hepatoencephalopathy (HE), changes in the organ morphology of rats affect the balance of metabolites of the tricarboxylic acid (TCA) cycle and metabolites of the glutamine-glutamate (Gln-Glu) cycle, namely α-ketoglutarate (αKG) and α-ketoglutaramate (αKGM), as well as the enzymes associated with them, ω-amidase (ωA) and glutamine transaminase (GTK). This model of rats was obtained as a result of 2-22 weeks of consumption by animals of hepatotoxin thioacetamide (TAA) added to drinking water at a concentration of 0.4 g/L. The control (n = 26) and TAA-induced (n = 55) groups of rats consisted of 11 cohorts each. The control cohorts consisted of 2-4 rats, and the TAA-induced cohorts consisted of 4-7 individuals. Every two weeks, samples of blood plasma, liver, kidney, and brain tissues were taken from the next cohort of rats (a total of 320 samples). By the end of the experiment, irreversible morphological changes were observed in the organs of rats: the weight of the animals was reduced up to ~45%, the weight of the kidneys up to 5%, the brain up to ~20%, and the weight of the liver increased up to ~20%. The analysis revealed: (i) a decrease in the activity of ωA and GTK in the tissues of the brain, kidneys, and liver of rats with chronic HE (by ~3, 40, and 65% and ~10, 60, and 70%, respectively); and (ii) the appearance of a significant imbalance in the content of metabolites of the Gln-Glu cycle, αKG, and αKGM. It is indicative that a ~1.5-12-fold increase in the level of αKG in the blood plasma and tissues of the organs of rats with chronic HE was accompanied by a synchronous, ~1.2-2.5-fold decrease in the level of αKGM. The data obtained indicate an essential involvement of the Gln-Glu cycle in the regulation of energy metabolism in rats under conditions of chronic HE. Attention is focused on the significance of the αKG/αKGM ratio, which can act as a potential marker for diagnosing the degree of HE development.

Development of a serum-free medium for myoblasts long-term expansion and 3D culture for cell-based meat.

Cell-based meat technology provides an effective method to meet the demand for meat, while also posing a huge challenge to the expansion of myoblasts. It is difficult to develop serum-free medium suitable for long-term culture and large-scale expansion of myoblasts, which causes limited understanding of myoblasts expansion. Therefore, this study used C2C12 myoblasts as model cells and developed a serum-free medium for large-scale expansion of myoblasts in vitro using the Plackett-Burman design. The serum-free medium can support short-term proliferation and long-term passage of C2C12 myoblasts, while maintaining myogenic differentiation potential well, which is comparable to those of growth medium containing 10% fetal bovine serum. Based on the C2C12 myoblasts microcarriers serum-free culture system established in this study, the actual expansion folds of myoblasts can reach 43.55 folds after 7 days. Moreover, cell-based meat chunks were preliminarily prepared using glutamine transaminase and edible pigments. The research results provide reference for serum-free culture and large-scale expansion of myoblasts in vitro, laying the foundation for cell-based meat production. PRACTICAL APPLICATION: This study developed a serum-free medium suitable for long-term passage of myoblasts and established a microcarrier serum-free culture system for myoblasts, which is expected to solve the problem of serum-free culture and large-scale expansion of myoblasts in cell culture meat production.

Effects of silybin supplementation on growth performance, serum indexes and liver transcriptome of Peking ducks.

As an emerging feed additive extracted from the traditional herb milk thistle, silybin has few applications and studies in Peking ducks. The aim of this study was to explore the practical significance of silymarin application in Peking ducks and to provide more theoretical support for the application of silymarin in livestock and poultry production. A total of 156 1-day-old healthy Peking ducks were randomly divided into four groups and supplemented with 0 mg/kg (control group), 400 mg/kg (S400), 800 mg/kg (S800) and 1,600 mg/kg (S1600) of silybin in the diets at day 14, to investigate the effects of silymarin on the growth, serum indexes and liver transcriptome of Peking ducks. The whole experiment lasted until day 42, and the sample collection was scheduled to take place in the morning. A substantial inprovement in average daily gain (ADG) and a decrease in feed conversion ratio (FCR) occurred in the S1600 group on days 14-28 compared to the control group (p < 0.05). The FCRs of other additive groups in the same period showed the same results. Supplementation of diets with silybin significantly increased serum IgA levels and when 1,600 mg/kg of silybin was given, levels of TNF-α and IL-6 were also significantly decreased (p < 0.05). In addition, we observed that the S1600 group had a significantly lower (p < 0.05) glutamine transaminase and an increased (p < 0.05) T-SOD level in the S400 group (p < 0.05). Liver transcriptome sequencing showed that 71 and 258 differentially expressed genes (DEGs) were identified in the S400 and S1600 groups, respectively, compared with the control group. DEGs related to cell composition and function, antigen processing and presentation were up-regulated, while DEGs related to insulin resistance and JAK-STAT were down-regulated. Conclusively, silybin can be used as a feed additive to improve the growth performance and health status of Peking ducks.

Effects of high hydrostatic pressure sterilisation and thermal sterilisation combined with glutamine transaminase treatment on the properties of yoghurt

The effects of conventional thermal sterilisation and high hydrostatic pressure (HHP) sterilisation combined with glutamine transaminase (TGase) on the characteristics of set yoghurt were investigated. Upon thermal and HHP treatment, the addition of an appropriate amount of TGase had no significant effect on the acidity and viable bacteria count of the yoghurt. However, the water holding capacity, viscosity, and firmness of the yoghurt significantly improved. When yoghurt was thermal treated combined with TGase and with HHP followed by TGase, the optimal values of the yoghurt indicators were achieved when 2 U g−1 TGase was added. When TGase was added at 4 U g−1 before HHP treatment (TGase-HHP), the optimal values of the yoghurt indicators were achieved. It was clear that the proteins in TGase-HHP yoghurt exposed more TGase binding sites than the other two types of treatment. In addition, tests were performed with chroma meters, electronic tongues and electronic noses.

Colon-targeted EMSCs conditional medium hydrogel for treatment of ulcerative colitis in mice

Oral ecto-mesenchymal stem cells-conditional medium (EMSCs-CM) is a promising strategy for treating ulcerative colitis (UC). However, this therapy is currently limited by the harsh gastrointestinal environment and poor colonic targeting ability. Herein, a glutamine transaminase 2 (TG2) crosslinked EMSCs-CM hydrogel (EMSCs-CM-Gel) was fabricated by combining EMSCs-CM with negatively charged γ-polyglutamic acid (γ-PGA) hydrogel. Intestinal epithelial cell 6 (IEC-6) was applied to construct a cell model with lipopolysaccharide to evaluate the anti-inflammatory potential of EMSCs-CM in vitro. The crosslinked gel was orally administered to mice in liquid form to access the effects of EMSCs-CM-Gel in vivo. This study was based on the fact that the hydrogel containing EMSCs-CM has negative charges, which ensure it remains at the positively charged inflamed colon tissue. The EMSCs-CM could continuously be released in the damaged colon mucosa along with the degradation of the γ-PGA hydrogel. Immunofluorescence and western blot were performed to assess the effects of EMSCs-CM-Gel on mice. The results in vivo showed that EMSCs-CM-Gel could significantly suppress the expression of inflammatory cytokines, prevent the shortening of the length of the intestine and repair the intestinal barrier. Collectively, our findings provided a novel colon-targeted strategy, hoping to benefit UC patients a lot.

Silencing of Glutamine: Fructose-6-Phosphate Aminotransferase Impairs Growth and Development in Sogatella furcifera (Hemiptera: Delphacidae).

Glutamine: fructose-6-phosphate aminotransferase (GFAT), the fourth enzyme in the chitin synthesis pathway, exerts wide-ranging effects on the growth and development of organisms. However, the role of GFAT in Sogatella furcifera remains unknown. In this study, the functional significance of the GFAT gene of S. furcifera was analyzed using a reverse transcription-polymerase chain reaction and RNA interference (RNAi) analyses. The complementary DNA sequence of SfGFAT was 3162 bp in length and contained a 2067 bp open reading frame encoding 688 amino acid residues. Structural domain analysis indicated that the SfGFAT protein consisted of one glutamine aminotransferase class 2 domain and two sugar isomerase domains. Expression profile analysis revealed that SfGFAT was expressed throughout the egg, nymph, and adult phases and was strongly expressed on the first day of each nymph stage and in the integuments of five tissues. RNAi results revealed that SfGFAT gene silencing significantly inhibited the mRNA expression of the target gene and resulted in severe mortality among S. furcifera. In summary, these findings demonstrate that SfGFAT plays a critical role in the development of S. furcifera. Moreover, these results may aid in the development of methods to control the spread of S. furcifera.

Hepatic adenoma in a 7-year-old girl: a case report and literature review

BackgroundHepatocellular adenomas (HCAs) are rare benign tumors of the liver that occur predominantly in women taking oral contraceptives. In children, HCAs comprise < 5% of hepatic tumors. We report a case of HCAs in a 7-year-old girl with estrogen and glucose imbalance.Case presentationA 7-year-old girl was presented to our hospital with bilateral breast enlargement for 2 months, polydipsia, polyuria, polyphagia, hyperglycemia, and significant weight gain. Computed tomography (CT) showed a 7.2 cm×6.9 cm×5.3 cm round-shaped mass in the left inner lobe of the liver, ovarian ultrasound showed multiple follicles in the ovaries bilaterally, and cranial magnetic resonance imaging (MRI) showed an enlarged superior pituitary. Hematological and biochemical results were as follows: fasting glucose was 19.7 mmol/L, estradiol was 122.9 pmol/L, follicle-stimulating hormone 10.81 IU/L, luteinizing hormone 10.99 IU/L, insulin-like growth factor 1,513 ng/mL, glutamine aminotransferase 86 U/L, and alkaline phosphatase 362 U/L. Thyroid functions, methemoglobin, fetal protein, carcinoembryonic antigen, and chorionic gonadotropin were normal. The patient had a complete surgical resection of the liver tumor, and the postoperative histopathological diagnosis was HCAs. After the surgery, insulin was injected and the glucose levels were stable. During the 36-month follow-up period, neither tumor recurrence nor significant abnormalities were detected using color Doppler ultrasound of the liver. The child’s precocious puberty is currently under control.ConclusionsHCAs are particularly rare in children with liver tumors, and risk factors for the development of HCAs in children include sex hormone imbalance, obesity, Fanconi anemia (FA), glycogen storage diseases (GSDs) type I, III, and IV, galactosemia, immunodeficiency, congenital portosystemic shunts (CPSS), cardiac hepatopathy status-post Fontan procedure, Hurler syndrome, familial adenomatous polyposis, germline HNF1A mutations, and maturity-onset diabetes of the young type 3. Most HCAs are detected during a physical examination without clinical symptoms, and some patients may present with symptoms such as abdominal pain, abdominal distension, and abdominal masse. Serum liver function tests can show increased alkaline phosphatase (ALP) and γ- glutamyl transferase (GT), whereas α-Fetoprofein (AFP) levels are normal. The definitive diagnosis relies mainly on histopathological examination. Because HCAs can rupture and bleed and become malignant. Early surgical treatment is recommended after detection.

Preparation and molecular simulation of an environmentally friendly dust-fixing agent based on chitosan-gelatin.

In order to solve the hazard of coal mine dust, a dust-fixing agent (GC-TG-JFC) was prepared with gelatin, chitosan, octadecanol polyoxyethylene ether, and glutamine transaminase. The experimental conditions and the formulation were optimized by response surface method. The ratio of gelatin, chitosan, octadecanol polyoxyethylene ether, and glutamine transaminase was 0.405:0.211:0.095:0.286 and the dilution ratio was 1:30. The results of product performance test showed that the dust fixation rate could reach 99.95% when the wind speed was 9 m/s. The viscosity of the diluted solution was 42.5 mPa·s. The Forcite module in Materials studio software was used to analyze and calculate the radial distribution concentration, diffusion coefficient, and binding energy of the solution. The results showed that GC-TG-JFC migrated more water molecules to the surface of coal through the action of van der Waals force and hydrogen bond. In addition, the binding energy of water molecules increased and the diffusion coefficient decreased, which improved the binding ability of water molecules with coal. It could be found that GC-TG-JFC had good dust fixation performance by combining experiment and molecular dynamics method.

Gel Properties and Structural Characteristics of Composite Gels of Soy Protein Isolate and Silver Carp Protein.

Problems with silver carp protein (SCP) include a strong fishy odor, low gel strength of SCP surimi, and susceptibility to gel degradation. The objective of this study was to improve the gel quality of SCP. The effects of the addition of native soy protein isolate (SPI) and SPI subjected to papain-restricted hydrolysis on the gel characteristics and structural features of SCP were studied. The β-sheet structures in SPI increased after papain treatment. SPI treated with papain was crosslinked with SCP using glutamine transaminase (TG) to form a composite gel. Compared with the control, the addition of modified SPI increased the hardness, springiness, chewiness, cohesiveness, and water-holding capacity (WHC) of the protein gel (p < 0.05). In particular, the effects were most significant when the degree of SPI hydrolysis (DH) was 0.5% (i.e., gel sample M-2). The molecular force results demonstrated that hydrogen bonding, disulfide bonding, and hydrophobic association are important molecular forces in gel formation. The addition of the modified SPI increases the number of hydrogen bonds and the disulfide bonds. Scanning electron microscopy (SEM) analysis showed that the papain modifications allowed the formation of a composite gel with a complex, continuous, and uniform gel structure. However, the control of the DH is important as additional enzymatic hydrolysis of SPI decreased TG crosslinking. Overall, modified SPI has the potential to improve SCP gel texture and WHC.

Residual Amino Acid Imbalance in Rats during Recovery from Acute Thioacetamide-Induced Hepatic Encephalopathy Indicates Incomplete Healing.

The delayed consequences of the influence of hepatic encephalopathy (HE) on the metabolism of animals have not been studied enough. We have previously shown that the development of acute HE under the influence of the thioacetamide (TAA) toxin is accompanied by pathological changes in the liver, an imbalance in CoA and acetyl CoA, as well as a number of metabolites of the TCA cycle. This paper discusses the change in the balance of amino acids (AAs) and related metabolites, as well as the activity of glutamine transaminase (GTK) and ω-amidase enzymes in the vital organs of animals 6 days after a single exposure to TAA. The balance of the main AAs in blood plasma, liver, kidney, and brain samples of control (n = 3) and TAA-induced groups (n = 13) of rats that received the toxin at doses of 200, 400, and 600 mg/kg was considered. Despite the apparent physiological recovery of the rats at the time of sampling, a residual imbalance in AA and associated enzymes persisted. The data obtained give an idea of the metabolic trends in the body of rats after their physiological recovery from TAA exposure and may be useful for prognostic purposes when choosing the necessary therapeutic agents.

Urinary trihalomethane concentrations and liver function indicators: a cross-sectional study in China.

While it is known that exposure to disinfection by-products (DBPs), including trihalomethanes (THMs), impairs liver function, few epidemiological studies have explored this association. Here, we determined the concentrations of four urinary trihalomethanes (chloroform [TCM], and three Br-THMs, bromodichloromethane [BDCM], dibromochloromethane [DBCM], and bromoform [TBM]), and nine serum liver function indicators in 182 adults ≥ 18years of age, examined at a medical examination center in Wuxi, China, in 2020 and 2021. Generalized linear model analysis revealed positive associations between urinary DBCM and alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), total protein (TP), and albumin (ALB). Urinary Br-THMs and total THMs (TTHMs) were positively associated with ALT, AST, TBIL, indirect bilirubin (IBIL), TP, and ALB (all P < 0.05). Urinary THMs were not associated with alkaline phosphatase (ALP) or glutamine transaminase (GGT) (all P > 0.05). Generalized additive model-based penalized regression splines were used to confirm these associations. In conclusion, THM exposure was associated with altered serum biomarkers of liver function.

Chemistry, biochemistry and clinical relevance of the glutamine metabolite α-ketoglutaramate/2-hydroxy-5-oxoproline

In the glutaminase II pathway (which we now refer to as the glutamine transaminase-ω-amidase (GTωA) pathway), l-glutamine is transaminated to α-ketoglutaramate (KGM), which, in turn, is hydrolyzed to α-ketoglutarate and ammonia by an enzyme known as ω-amidase. Despite the fact that the GTωA pathway was discovered more than 70 years ago, and is widespread in nature, the pathway has received limited attention. This is partly due to the broad amino acid/α-keto acid specificity of the glutamine transaminases, which has led to confusion over nomenclature and in assigning precise biological roles. Secondly, the α-keto acid product of glutamine transaminases – KGM – has not, until recently, become available in pure form. Here, we briefly discuss the metabolic importance of the GTωA pathway in microorganisms, plants and mammals. We pay special attention to the chemistry of KGM and methods for its synthesis. We discuss the importance of KGM as a biomarker for hyperammonemic diseases. We provide evidence that the GTωA pathway satisfies, in part, ‘glutamine addiction’ in a variety of cancer cells. We show that the anti-cancer drugs 6-diazo-5-oxo-l-norleucine and l-azaserine are transaminase and β-lyase substrates of glutamine transaminase K, respectively. We suggest that there is a pressing need for the development of: (1) inexpensive and scaled-up procedures for the synthesis of KGM to facilitate research on the biological importance of the GTωA pathway in mammalian and human tissues and in agricultural research; and (2) potent and selective inhibitors of ω-amidase, both as anti-cancer agents and as a means for investigating the detailed enzyme mechanism.

Enzyme-regulated NO programmed to release from hydrogel-forming microneedles with endogenous/photodynamic synergistic antibacterial for diabetic wound healing

The infection-prone wound pathology microenvironment leads to ulceration and difficult healing of diabetic wounds, which seriously affects the quality of survival of patients. In this study, natural polymer materials gelatin and polylysine were used as substrates. By introducing iron/tannic acid (FeIIITA) composite nanoparticles with excellent photothermal properties into the system, the glutamine residues of gelatin were crosslinked with the primary ammonia of polylysine by glutamine aminotransferase. A nanocomposite hydrogel with excellent antibacterial ability and NO production was constructed it was used to improve the clinical problems of diabetes wounds that were difficult to vascularize and easy to be infected. Under the premise of maintaining its structural stability, the hydrogel can be customized to meet the needs of different mechanical strengths by adjusting the ratios to match different diabetic wounds. Meanwhile, the photothermal effect of FeIIITA nanoparticles can synergize with the endogenous antibacterial ability of polylysine to improve the antibacterial efficacy of hydrogels. The potential of hydrogel to promote intracellular NO production was confirmed by fluorescent staining. Microneedle patches prepared from hydrogel can be applied to diabetic wounds, which can achieve NO deep release. Its anti-inflammatory and angiogenic abilities are also useful in achieving effective healing of diabetic wounds.

Human cytosolic transaminases: side activities and patterns of discrimination towards physiologically available alternative substrates

Transaminases play key roles in central metabolism, transferring the amino group from a donor substrate to an acceptor. These enzymes can often act, with low efficiency, on compounds different from the preferred substrates. To understand what might have shaped the substrate specificity of this class of enzymes, we examined the reactivity of six human cytosolic transaminases towards amino acids whose main degradative pathways do not include any transamination. We also tested whether sugars and sugar phosphates could serve as alternative amino group acceptors for these cytosolic enzymes. Each of the six aminotransferases reacted appreciably with at least three of the alternative amino acid substrates in vitro, albeit at usually feeble rates. Reactions with L-Thr, L-Arg, L-Lys and L-Asn were consistently very slow—a bias explained in part by the structural differences between these amino acids and the preferred substrates of the transaminases. On the other hand, L-His and L-Trp reacted more efficiently, particularly with GTK (glutamine transaminase K; also known as KYAT1). This points towards a role of GTK in the salvage of L-Trp (in cooperation with ω-amidase and possibly with the cytosolic malate dehydrogenase, MDH1, which efficiently reduced the product of L-Trp transamination). Finally, the transaminases were extremely ineffective at utilizing sugars and sugar derivatives, with the exception of the glycolytic intermediate dihydroxyacetone phosphate, which was slowly but appreciably transaminated by some of the enzymes to yield serinol phosphate. Evidence for the formation of this compound in a human cell line was also obtained. We discuss the biological and evolutionary implications of our results.

Clinical significance of serum ferritin in patients with systemic sclerosis.

ObjectiveThe purpose of this study was to explore the clinical significance of serum ferritin (SF) in patients with systemic sclerosis (SSc).MethodsThe levels of SF were measured in 115 patients with SSc and 117 healthy controls (HCs). Clinical characteristics and laboratory indexes between the high ferritin SSc group and the normal ferritin SSc group were analyzed.ResultsThe level of SF in SSc patients was significantly higher than that in HCs (319.78 [179, 554.33] ng/ml vs. 99 [49.03, 164.29] ng/ml, p < 0.01). Compared with the normal ferritin SSc group, the high ferritin SSc group was more likely to develop skin diffuse cutaneous SSc, fingertip arthralgia, and cardiac involvement. In addition, the levels of glutamine transaminase (GGT), alanine aminotransferase (ALT), creatine kinase (CK), creatine kinase isoenzyme‐MB (CK‐MB), lactate dehydrogenase (LD), immunoglobulin G (IgG), immunoglobulin A (IgA), C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR), and the positive rate of anti‐Scl70 antibody in the high ferritin SSc group were significantly higher (each p < 0.05). SF was positively correlated with GGT, ALT, CK, CK‐MB, LD, IgA, CRP, and ESR (each p < 0.05). Multiple linear regression analysis showed that cardiac involvement, ALT, and ESR were independent influencing factors of SF in SSc.ConclusionOur study shows that the level of SF in patients with SSc is increased, and the elevated SF is related to abnormal liver function, myocardial involvement, inflammatory status, and production of autoantibodies in SSc. Cardiac involvement, ALT, and ESR are independent factors affecting SF in SSc.

Cysteine conjugate beta-lyase 2 (CCBL2) expression as a prognostic marker of survival in breast cancer patients

ObjectiveCysteine conjugate beta-lyase 2 (CCBL2), also known as kynurenine aminotransferase 3 (KAT3) or glutamine transaminase L (GTL), plays an essential role in transamination and cytochrome P450. Its correlation with some other cancers has been explored, but breast cancer (BC) not yet.MethodsThe mRNA and protein expression of CCBL2 in BC cell lines and patient samples were detected by RT-qPCR and immunohistochemistry (IHC). BC patients’ clinical information and RNA-Seq expression were acquired via The Cancer Genome Atlas (TCGA) database. Patients were categorized into high/low CCBL2 expression groups based on the optimal cutoff value (8.973) determined by receiver operating characteristic (ROC) curve. We investigated CCBL2 and clinicopathological characteristics’ relationship using Chi-square tests, estimated diagnostic capacity using ROC curves and drew survival curves using Kaplan–Meier estimate. We compared survival differences using Cox regression and externally validated using Gene Expression Omnibus (GEO) database. We evaluated enriched signaling pathways using gene set enrichment analysis (GSEA), explored CCBL2 and relevant genes’ relationship using tumor immunoassay resource (TIMER) databases and used the human protein atlas (HPA) for pan-cancer analysis and IHC.ResultsCCBL2 was overexpressed in normal human cell lines and tissues. CCBL2 expression was lower in BC tissues (n = 1104) than in normal tissues (n = 114), validated by GEO database. Several clinicopathologic features were related to CCBL2, especially estrogen receptor (ER), progesterone receptor (PR) and clinical stages. The low expression group exhibited poor survival. CCBL2’s area under curve (AUC) analysis showed finite diagnostic capacity. Multivariate cox-regression analysis indicated CCBL2 independently predicted BC survival. GSEA showed enriched pathways: early estrogen response, MYC and so on. CCBL2 positively correlated with estrogen, progesterone and androgen receptors. CCBL2 was downregulated in most cancers and was associated with their survival, including renal and ovarian cancers.ConclusionsLow CCBL2 expression is a promising poor BC survival independent prognostic marker.

Effect of Adding Glutamine Transaminase on the Quality of Set-style Yogurt

Effect of Adding Glutamine Transaminase on the Quality of Set-style Yogurt

Comprehensive Metabolic Profiling of MYC-Amplified Medulloblastoma Tumors Reveals Key Dependencies on Amino Acid, Tricarboxylic Acid and Hexosamine Pathways.

Simple SummaryThe oncogene MYC alters cellular metabolism. Medulloblastoma is the most common malignant pediatric brain tumor. MYC-amplified medulloblastoma has a poor prognosis, and the metabolism of MYC-amplified medulloblastoma is poorly understood. We performed comprehensive metabolic profiling of MYC-amplified medulloblastoma and found increased reliance on potentially targetable pathways. We also found that the metabolism of MYC-amplified cell lines differed from orthotopic brain tumors in vitro and in flank tumors, suggesting that analyses conducted in vitro or in flank tumors may miss key vulnerabilities.Reprograming of cellular metabolism is a hallmark of cancer. Altering metabolism allows cancer cells to overcome unfavorable microenvironment conditions and to proliferate and invade. Medulloblastoma is the most common malignant brain tumor of children. Genomic amplification of MYC defines a subset of poor-prognosis medulloblastoma. We performed comprehensive metabolic studies of human MYC-amplified medulloblastoma by comparing the metabolic profiles of tumor cells in three different conditions—in vitro, in flank xenografts and in orthotopic xenografts in the cerebellum. Principal component analysis showed that the metabolic profiles of brain and flank high-MYC medulloblastoma tumors clustered closely together and separated away from normal brain and in vitro MYC-amplified cells. Compared to normal brain, MYC-amplified medulloblastoma orthotopic xenograft tumors showed upregulation of the TCA cycle as well as the synthesis of nucleotides, hexosamines, amino acids and glutathione. There was significantly higher glucose uptake and usage in orthotopic xenograft tumors compared to flank xenograft tumors and cells in culture. In orthotopic tumors, glucose was the main carbon source for the de novo synthesis of glutamate, glutamine and glutathione through the TCA cycle. In vivo, the glutaminase II pathway was the main pathway utilizing glutamine. Glutathione was the most abundant upregulated metabolite in orthotopic tumors compared to normal brain. Glutamine-derived glutathione was synthesized through the glutamine transaminase K (GTK) enzyme in vivo. In conclusion, high MYC medulloblastoma cells have different metabolic profiles in vitro compared to in vivo, and key vulnerabilities may be missed by not performing in vivo metabolic analyses.