Phytochemical characterization of Morus nigra fruit ultrasound-assisted ethanolic extract for its cardioprotective potential.

The current work investigated the phytochemical profile of ultrasound-assisted ethanolic extract of Morus nigra (M. nigra) fruit. FTIR analysis of M. nigra fruit extract revealed the presence of alcohols (O-H), alkanes (C-H stretch), alkenes (C=C), and alkynes (C≡C). The HPLC analysis quantified the quercetin, gallic acid, vanillic acid, chlorogenic acid, syringic acid, cinnamic acid, sinapic acid, and kaempferol. Furthermore, the cardioprotective activity of ethanolic extract of M. nigra fruit was investigated. Cholesterol supplementation (2%) in the daily diet and exposure to cigarette smoke (2 cigarettes twice a day) were to induce hypertension in rats. The experimental animals were categorized into four groups: G0 (negative control), G1 (positive control), G2 (standard drug), and G3 (M. nigra fruit). The fruit extract administration at 300 mg/kg BW/day orally for 2 months significantly (p < .001) enhanced the activities of serum and cardiac tissue antioxidants in hypertensive rats. Meanwhile, the fruit extract reduced the elevated serum lipid profile while significantly increasing the high-density lipoproteins in G3 than G1 and G2. The increase in blood pressure, liver transaminases, and serum lactate dehydrogenase also reduced significantly in M. nigra fruit extract-treated rats. Histopathological findings revealed mild normalization of cardiac myocytes with central nuclei, branching, and cross-striations. Consequently, the M. nigra fruit extract exerted the cardioprotective potential via increasing the antioxidant enzymes and reducing the lipids, lactate dehydrogenase, liver transaminases, and blood pressure. The therapeutic potential of M. nigra fruit can be due to flavonols and phenolic acids. PRACTICAL APPLICATIONS: The present work quantified the Morus nigra fruit phytochemicals and its significant role in reducing lipid markers and blood pressure and improving antioxidant status in rats fed a hypercholesterolemic diet and exposed to cigarette smoke. Conclusively, the inclusion of M. nigra fruit in daily diet could improve the cardiac health of the individuals. Furthermore, the therapeutic potential of M. nigra fruit and its isolated constituents in modulating the gene expression against cardiac problems can explore after clinical trials and standardization in higher animals.

Phase 1-2 Trial of AAVS3 Gene Therapy in Patients with Hemophilia B.

BACKGROUND: FLT180a (verbrinacogene setparvovec) is a liver-directed adeno-associated virus (AAV) gene therapy that uses a synthetic capsid and a gain-of-function protein to normalize factor IX levels in patients with hemophilia B. METHODS: In this multicenter, open-label, phase 1-2 trial, we assessed the safety and efficacy of varying doses of FLT180a in patients with severe or moderately severe hemophilia B (factor IX level, ≤2% of normal value). All the patients received glucocorticoids with or without tacrolimus for immunosuppression to decrease the risk of vector-related immune responses. After 26 weeks, patients were enrolled in a long-term follow-up study. The primary end points were safety and efficacy, as assessed by factor IX levels at week 26. RESULTS: Ten patients received one of four FLT180a doses of vector genomes (vg) per kilogram of body weight: 3.84×1011 vg, 6.40×1011 vg, 8.32×1011 vg, or 1.28×1012 vg. After receiving the infusion, all the patients had dose-dependent increases in factor IX levels. At a median follow-up of 27.2 months (range, 19.1 to 42.4), sustained factor IX activity was observed in all the patients except one, who resumed factor IX prophylaxis. As of the data-cutoff date (September 20, 2021), five patients had normal factor IX levels (range, 51 to 78%), three patients had levels from 23 to 43%, and one had a level of 260%. Of the reported adverse events, approximately 10% were related to FLT180a and 24% to immunosuppression. Increases in liver aminotransferase levels were the most common FLT180a-related adverse events. Late increases in aminotransferase levels occurred in patients who had received prolonged tacrolimus beyond the glucocorticoid taper. A serious adverse event of arteriovenous fistula thrombosis occurred in the patient with high factor IX levels. CONCLUSIONS: Sustained factor IX levels in the normal range were observed with low doses of FLT180a but necessitated immunosuppression with glucocorticoids with or without tacrolimus. (Funded by Freeline Therapeutics; ClinicalTrials.gov numbers, NCT03369444 and NCT03641703; EudraCT numbers, 2017-000852-24 and 2017-005080-40.).

Pediatric Autoimmune Liver Diseases: Autoimmune Hepatitis and Primary Sclerosing Cholangitis.

In chronic hepatitis, a broad differential diagnosis should be considered to accurately identify the cause(s) of liver injury. Autoimmune liver diseases (autoimmune hepatitis, primary sclerosing cholangitis, overlap syndrome) can occur in the setting of limited symptoms; therefore, a high index of suspicion and appropriate diagnostic workup should be performed. Most children with autoimmune hepatitis achieve sustained remission with medical therapy; however, there are no equivalent therapies for primary sclerosing cholangitis that impact the progression of disease. Research should include biomarker studies to predict histologic remission in autoimmune hepatitis and mechanistic studies to define future treatment targets for primary sclerosing cholangitis.

Fenebrutinib in H1 antihistamine-refractory chronic spontaneous urticaria: a randomized phase 2 trial.

Bruton's tyrosine kinase (BTK) is crucial for FcεRI-mediated mast cell activation and essential for autoantibody production by B cells in chronic spontaneous urticaria (CSU). Fenebrutinib, an orally administered, potent, highly selective, reversible BTK inhibitor, may be effective in CSU. This double-blind, placebo-controlled, phase 2 trial (EudraCT ID 2016-004624-35 ) randomized 93 adults with antihistamine-refractory CSU to 50 mg daily, 150 mg daily and 200 mg twice daily of fenebrutinib or placebo for 8 weeks. The primary end point was change from baseline in urticaria activity score over 7 d (UAS7) at week 8. Secondary end points were the change from baseline in UAS7 at week 4 and the proportion of patients well-controlled (UAS7 ≤ 6) at week 8. Fenebrutinib efficacy in patients with type IIb autoimmunity and effects on IgG-anti-FcεRI were exploratory end points. Safety was also evaluated. The primary end point was met, with dose-dependent improvements in UAS7 at week 8 occurring at 200 mg twice daily and 150 mg daily, but not at 50 mg daily of fenebrutinib versus placebo. Asymptomatic, reversible grade 2 and 3 liver transaminase elevations occurred in the fenebrutinib 150 mg daily and 200 mg twice daily groups (2 patients each). Fenebrutinib diminished disease activity in patients with antihistamine-refractory CSU, including more patients with refractory type IIb autoimmunity. These results support the potential use of BTK inhibition in antihistamine-refractory CSU.

Familiarity Breeds Strategy: In Silico Untangling of the Molecular Complexity on Course of Autoimmune Liver Disease-to-Hepatocellular Carcinoma Transition Predicts Novel Transcriptional Signatures.

Autoimmune liver diseases (AILD) often lead to transformation of the liver tissues into hepatocellular carcinoma (HCC). Considering the drawbacks of surgical procedures in such cases, need of successful non-invasive therapeutic strategies and treatment modalities for AILD-associated-HCC still exists. Due to the lack of clear, sufficient knowledge about factors mediating AILD-to-HCC transition, an in silico approach was adopted to delineate the underlying molecular deterministic factors. Parallel enrichment analyses on two different public microarray datasets (GSE159676 and GSE62232) pinpointed the core transcriptional regulators as key players. Correlation between the expression kinetics of these transcriptional modules in AILD and HCC was found to be positive primarily with the advancement of hepatic fibrosis. Most of the regulatory interactions were operative during early (F0-F1) and intermediate fibrotic stages (F2-F3), while the extent of activity in the regulatory network considerably diminished at late stage of fibrosis/cirrhosis (F4). Additionally, most of the transcriptional targets with higher degrees of connectivity in the regulatory network (namely DCAF11, PKM2, DGAT2 and BCAT1) may be considered as potential candidates for biomarkers or clinical targets compared to their low-connectivity counterparts. In summary, this study uncovers new possibilities in the designing of novel prognostic and therapeutic regimen for autoimmunity-associated malignancy of liver in a disease progression-dependent fashion.

Protease inhibitor-based direct-acting antivirals are associated with increased risk of aminotransferase elevations but not hepatic dysfunction or decompensation.

BACKGROUND & AIMS: Cases of acute liver injury (ALI) have been reported among chronic HCV-infected patients receiving protease inhibitor (PI)-based direct-acting antiviral (DAA) regimens, but no analyses have compared the risk of ALI in patients receiving PI- vs. non-PI-based DAAs. Thus, we compared the risk of 3 ALI outcomes between patients (by baseline Fibrosis-4 [FIB-4] group) receiving PI-based or non-PI-based DAAs. METHODS: We conducted a cohort study of 18,498 patients receiving PI-based DAA therapy (paritaprevir/ritonavir/ombitasvir±dasabuvir, elbasvir/grazoprevir, glecaprevir/pibrentasvir) matched 1:1 on propensity score to those receiving non-PI-based DAAs (sofosbuvir/ledipasvir, sofosbuvir/velpatasvir) in the 1945-1965 Veterans Birth Cohort (2014-2019). During exposure to DAA therapy, we determined development of: i) alanine aminotransferase (ALT) >200 U/L, ii) severe hepatic dysfunction (coagulopathy with hyperbilirubinemia), and iii) hepatic decompensation. We used Cox regression to determine hazard ratios (HRs) with 95% CIs for each ALI outcome within groups defined by baseline FIB-4 (≤3.25; >3.25). RESULTS: Among patients with baseline FIB-4 ≤3.25, those receiving PIs had a higher risk of ALT >200 U/L (HR 3.98; 95% CI 2.37-6.68), but not severe hepatic dysfunction (HR 0.67; 95% CI 0.19-2.39) or hepatic decompensation (HR 1.01; 95% CI 0.29-3.49), compared to those receiving non-PI-based regimens. For those with baseline FIB-4 >3.25, those receiving PIs had a higher risk of ALT >200 U/L (HR, 2.15; 95% CI 1.09-4.26), but not severe hepatic dysfunction (HR, 1.23 [0.64-2.38]) or hepatic decompensation (HR, 0.87; 95% CI 0.41-1.87), compared to those receiving non-PI-based regimens CONCLUSION: While risk of incident ALT elevations was increased in those receiving PI-based DAAs in both FIB-4 groups, the risk of severe hepatic dysfunction and hepatic decompensation did not differ between patients receiving PI- or non-PI-based DAAs in either FIB-4 group. LAY SUMMARY: Cases of liver injury have been reported among patients treated with protease inhibitor-based direct-acting antivirals for hepatitis C infection, but it is not clear if the risk of liver injury among people starting these drugs is increased compared to those starting non-protease inhibitor-based therapy. In this study, patients receiving protease inhibitor-based treatment had a higher risk of liver inflammation than those receiving a non-protease inhibitor-based treatment, regardless of the presence of pre-treatment advanced liver fibrosis/cirrhosis. However, the risk of severe liver dysfunction and decompensation were not higher for patients treated with protease inhibitor-based regimens.

Multicenter Analysis of Clinical Features and Prognosis of COVID-19 Patients with Hepatic Impairment.

Background/Aims: Recent data indicate the presence of liver enzyme abnormalities in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the clinical features and treatment outcomes of COVID-19 patients with abnormal liver enzymes. Methods: We performed a retrospective, multicenter study of 874 COVID-19 patients admitted to five tertiary hospitals from February 20 to April 14, 2020. Data on clinical features, laboratory parameters, medications, and treatment outcomes were collected until April 30, 2020, and compared between patients with normal and abnormal aminotransferases. Results: Abnormal aminotransferase levels were observed in 362 patients (41.1%), of which 94 out of 130 (72.3%) and 268 out of 744 (36.0%) belonged to the severe and non-severe COVID- 19 categories, respectively. The odds ratios (95% confidence interval) for male patients, patients with a higher body mass index, patients with severe COVID-19 status, and patients with lower platelet counts were 1.500 (1.029 to 2.184, p=0.035), 1.097 (1.012 to 1.189, p=0.024), 2.377 (1.458 to 3.875, p=0.001), and 0.995 (0.993 to 0.998, p>0.001), respectively, indicating an independent association of these variables with elevated aminotransferase levels. Lopinavir/ ritonavir and antibiotic use increased the odds ratio of abnormal aminotransferase levels after admission (1.832 and 2.646, respectively, both p<0.05). The median time to release from quarantine was longer (22 days vs 26 days, p=0.001) and the mortality rate was higher (13.0% vs 2.9%, p<0.001) in patients with abnormal aminotransferase levels. Conclusions: Abnormal aminotransferase levels are common in COVID-19 patients and are associated with poor clinical outcomes. Multivariate analysis of patients with normal aminotransferase levels on admission showed that the use of lopinavir/ritonavir and antibiotics was associated with abnormal aminotransferase levels; thus, careful monitoring is needed.

Species-specific neuronal localization of kynurenine aminotransferase-2 in the mouse cerebellum.

The immunohistochemical pattern of kynurenine aminotransferase-2 (KAT-2) - the key role enzyme in the production of neuroactive and neuroprotective kynurenic acid (KYNA) - was studied in the cerebellum of mice. It is known from literature that KAT-2 is localized mainly in astrocytes in different parts of the cerebrum. Kynurenine aminotransferase (KAT) activity in the cerebellum is relatively low and alternative production routes for KYNA have been described there. Therefore we examined the immunohistochemical pattern of KAT-2 in this part of the brain. Surprisingly, the cellular localization of KAT-2 in mice was proven to be unique; it localized characteristically in Purkinje cells and in some other types of neurons (not identified) but was not found in astrocytes nor microglia. The exclusive neuronal, but not glial localization of KAT-2 in the cerebellum is novel and may be related to its low activity and to the alternative pathways for KYNA production that have been described.

Variante "no clásica" o "atípica" del síndrome de Stauffer en paciente con carcinoma renal de células claras: reporte de caso / "Non-classical" or "atypical" variant of Stauffer syndrome in a patient with clear cell renal carcinoma: a case report

La manifestación paraneoplásica conocida como síndrome de Stauffer tiene una presentación atípica, caracterizada por ictericia y colestasis intrahepática. Presentamos el caso de un paciente de 53 años de edad, con antecedente de una masa renal derecha en plan de resección quirúrgica programada, con cuadro de evolución de dolor abdominal en hipocondrio derecho e ictericia. A su ingreso se documentó hepatoesplenomegalia, elevación de bilirrubinas a expensas de la directa, y de fosfatasa alcalina junto con elevación de transaminasas. Se descartaron causas obstructivas a nivel de vía biliar intra y extrahepática. No se documentaron metástasis o lesiones focales a nivel de parénquima, ni lesiones de etiología vascular que explicaran el cuadro. También se descartó hepatitis B, C e infección por VIH, por lo cual se consideró un probable síndrome de Stauffer. Fue llevado a nefrectomía intrahospitalaria, con posterior diagnóstico patológico compatible con carcinoma de células claras. Luego del procedimiento se normalizó la bioquímica hepática y se corrigió la ictericia. Es importante reconocer que la afectación hepática en el contexto de neoplasias, no es solo atribuida a metástasis a distancia, sino también a la existencia de síndromes paraneoplásicos como condicionantes.

The paraneoplastic manifestation known as Stauffer syndrome has an atypical presentation, characterized by jaundice and intrahepatic cholestasis. We present the case of a 53-year-old patient, with a history of a right renal mass with a planned surgical resection, who developed abdominal pain in the right upper quadrant and jaundice. Upon admission, hepatosplenomegaly, elevated bilirubin, at the expense of direct bilirubin, alkaline phosphatase and elevated transaminases were documented. Intra- and extrahepatic bile ducts obstruction were ruled out. There were no documented metastases or focal lesions at the level of the parenchyma, or lesions of vascular etiology that could explain the condition. Hepatitis B, C and HIV infection were also ruled out, and a probable Stauffer syndrome was considered. In-hospital nephrectomy was performed, with subsequent pathology compatible with clear cell carcinoma. After the procedure, liver biochemistry was normalized and jaundice was corrected. It is important to recognize that liver involvement in the context of neoplasms is not only attributed to distant metastases but to the existence of paraneoplastic syndromes as determining factors.

Estudio descriptivo de la esteatosis hepática y la morbilidad asociada en atención primaria. (Estudio ESTEATOAP) / Descriptive study of hepatic steatosis and associated morbidity in Primary Care. (ESTEATOAP Study)

OBJETIVO: Estudiar la prevalencia registrada de esteatosis hepática en atención primaria, así como la proporción de pacientes con diagnóstico de EHGNA que incluye el hígado graso simple no alcohólico (HGNA) y de esteatohepatitis no alcohólica frente a la esteatosis por otras causas. Además, se estudió la proporción de las morbilidades cardiometabólicas asociadas al HGNA. MATERIAL Y MÉTODOS: Estudio observacional descriptivo. La población de estudio es la de todos los pacientes con diagnóstico registrado de esteatosis hepática en un Centro de Salud urbano que atiende a una población de 25.747 mayores de 14 años. Se calculó un tamaño muestral de 229 pacientes. Se describen las características demográficas y clínicas asociadas. RESULTADOS: La prevalencia de esteatosis fue del 2,17%. Y de EHGNA del 1,51%. La media de edad de 62,42. Mujeres 114 mujeres (50,2%) y 113 varones (49,8%). Ciento cuarenta y siete (64,8%) fueron EHGNA y 64 (28,2%) fueron esteatosis por otras causas. La proporción de pacientes con EHGNA y transaminasas elevadas fue del 24,13% y la proporción de pacientes con EHGNA y elevación de GGT fue el 18,6%. Se ha encontrado una proporción elevada de EHGNA con factores de riesgo cardiometabólico: 93,9% de sobrepeso y obesidad, 55,1% de diabetes, 54,4% de hipertensión, 32,9% de síndrome metabólico, 35,2% hipertrigliceridemia y HDL de riesgo 19,6%. Entre los factores de riesgo cardiometabólicos y la EHGNA se encontró relación significativa en la diabetes, la obesidad y el síndrome metabólico. DISCUSIÓN: La prevalencia fue de solo el 1,51%, quizás por la escasa importancia que se da a esta enfermedad. Hay una proporción alta de EHGNA con factores de riesgo cardiometabólicos y más en la población general. Si se consideran todas las causas de esteatosis hay una asociación significativa entre obesidad, diabetes mellitus y síndrome metabólico con la EHGNA. CONCLUSIONES: La prevalencia registrada de EHGNA es muy inferior a la de los estudios poblacionales, además se ha encontrado una alta presencia de los factores cardiometabólicos en estos pacientes

OBJECTIVE: To study the recorded prevalence of hepatic steatosis in Primary Care, as well as the proportion of patients diagnosed with fatty liver diseases (FLD) including simple non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) versus steatosis by other causes. In addition, the proportion of cardiometabolic morbidities associated with NAFLD liver was studied. MATERIAL AND METHODS: A descriptive observational study was carried out on a population that included all patients with a recorded diagnosis of hepatic steatosis in an urban health centre that serves a population of 25,747 over the age of 14. A sample size of 229 patients was calculated. The demographic and clinical characteristics associated with hepatic steatosis are described. RESULTS: The prevalence of steatosis was 2.17% and 1.51% for NAFLD. The mean age was 62.42 years. The study included 114 (50.2%) women and 113 (49.8%) males. NAFLD was found in 147 (64.8%), and 64 (28.2%) were steatosis due to other causes. The proportion of patients with NAFLD and high transaminases was 24.13%, and the proportion of patients with NAFLD and GGT elevation was 18.6%. A high proportion of NAFLD had been found with cardiometabolic risk factors: 93.9% overweight and obesity, 55.1% diabetes, 54.4% hypertension, 32.9% metabolic syndrome, 35.2% hypertriglyceridaemia, and HDL risk 19.6%. A significant association was found between cardiometabolic risk factors and NAFLD in diabetes, obesity, and metabolic syndrome. DISCUSSION: Prevalence was only 1.51%, perhaps because of the low importance given to this disease. There is a high proportion of NAFLD with cardiometabolic risk factors and more in the general population. If all the causes of steatosis are considered there is a significant association between obesity, diabetes mellitus, and metabolic syndrome with NAFLD. CONCLUSIONS: The recorded prevalence of NAFLD is much lower than that of population studies, and a high presence of cardiometabolic factors has been found in these patients

Crocetin Improves Dengue Virus-Induced Liver Injury.

Dengue virus (DENV) infection is one of the most widespread mosquito-borne viral infections. Liver injury is commonly observed in severe DENV infection, and the present study aimed to examine the efficacy of crocetin treatment in an immunocompetent mouse model of DENV infection exhibiting liver injury. The efficacy of crocetin treatment in DENV-induced liver injury was assessed via both transaminase levels and histopathology analysis. A real-time polymerase chain reaction array was then used to describe the expression of 84 apoptosis-related genes. Using real-time RT-PCR and Western blot analysis, the gene expressions of host factors were investigated. Additionally, the effect of crocetin in NF-kB signaling during DENV infection was studied. We did not observe any significant reduction in virus production when DENV-infected mice were treated with crocetin. However, DENV-infected mice treated with crocetin showed reduced DENV-induced apoptosis. The real-time polymerase chain reaction array revealed pro-inflammatory cytokine expressions to be significantly reduced in the crocetin-treated DENV-infected mice. We also found that crocetin could effectively modulate antioxidant status in DENV-infected mice. Moreover, crocetin demonstrated the ability to reduce the nuclear translocation of NF-kB in DENV-infected mice. Our results suggest that crocetin treatment does not inhibit DENV replication in the liver of DENV-infected mice; however, we did find that crocetin improves host responses that reduce liver injury.

Experiencia clínica con tolvaptán en pacientes con poliquistosis renal / Clinical experience with tolvaptan in patients with polycystic kidney disease

No disponible

Prognostic significance of branched-chain amino acid transferase 1 and CD133 in triple-negative breast cancer.

BACKGROUND: Previous studies have shown that branched-chain amino acid transferase 1 (BCAT1) is associated with tumour progression in triple-negative breast cancer (TNBC). Furthermore, CD133 has emerged as a novel cancer stem cell marker for indicating tumour progression. However, the prognostic significance of these two markers remains to be verified. This study was conducted to investigate the correlation between BCAT1 and CD133 expression and clinicopathological features, as well as the prognosis of patients with TNBC. METHODS: The study cohort included 291 patients with TNBC. Tissue microarrays were constructed for both cancer and normal tissues. The expression of BCAT1 and CD133 was detected by immunohistochemical staining, and the levels were evaluated using an H-scoring system. Cut-off points for BCAT1 and CD133 expression were determined using receiver operating characteristic curves. RESULTS: The median follow-up time for the study participants was 68.73 months (range: 1.37-103.6 months). The 5-year disease-free survival (DFS) and overall survival (OS) rates of the 291 patients with TNBC were 72.51 and 82.47%, respectively. Higher levels of BCAT1 and CD133 expression independently indicated shorter DFS and OS. High levels of both BCAT1 and CD133 expression were detected in 36 (12.37%) patients, who had significantly shorter DFS and OS (both P < 0.001) compared to other patients. CONCLUSION: BCAT1 and CD133 can be considered as biomarkers with prognostic significance for TNBC.

Kynurenine Aminotransferases I, II and III Are Present in Saliva.

BACKGROUND/AIMS: Fluids of the human body such as serum, cerebrospinal fluid and saliva contain a wide variety of proteins. Because kynurenic acid (KYNA) has been detected in human saliva, we wondered if KYNA could be produced in saliva by KYNA-synthesising enzymes, namely the kynurenine aminotransferases KAT I, KAT II and KAT III. METHODS: Thirty samples of human saliva from control volunteers were investigated. KAT activity was measured in the presence of 1 mM pyruvate and 2 µM or 100 µM L-kynurenine and KYNA production was assessed by high-performance liquid chromatography. RESULTS: Saliva dose- and time-dependently produced KYNA. KAT activity ranged between 900 and 1050 pmol/mg protein/h: 900 for KAT I, 950 for KAT III and 1050 for KAT II. KYNA was synthesised in saliva at a physiological concentration of 2 µM L-kynurenine and at a higher concentration of 100 µM. Investigation of the distributions of the enzymes in saliva revealed that KAT I, KAT II and KAT III activity in a centrifuge-obtained pellet ranged from ~100% to 120%; in the supernatant, the percentage was between 0% and 20%. We observed a nonsignificant tendency for lower KAT activity in women's saliva than in men's. KATs present in saliva were sensitive to the GABA-transaminase inhibitor γ-acetylenic GABA, with a concentration of 100 µM γ-acetylenic GABA significantly blocking the formation of KYNA (50% of control, p < 0.05). Furthermore, KATs in saliva were sensitive to anti-dementia drugs, such as D-cycloserine and cerebrolysin, in an in vitro study. CONCLUSION: Our data revealed for the first time the presence of KAT I, KAT II and KAT III proteins in human saliva. KAT activity was found mostly in pelleted cells, suggesting their presence in salivary gland cells. KAT proteins in saliva are sensitive to drugs blocking KYNA formation. Our data indicate the presence of cells in saliva involved in the biochemical machinery of the kynurenine pathway. Their role in the digestive process remains to be clarified. We speculate that modulation of KYNA formation in the mouth by food and/or drugs might affect glutamate neurotransmission and cholinergic activity in the CNS and/or periphery and play a role under physiological as well as pathological conditions.

Effect of low-fat diets enriched with fruit purees on the biochemical markers of metabolic syndrome analogy induced-rats / Efecto de dietas bajas en grasa enriquecida con purés de frutas sobre marcadores bioquímicos en ratas inducidas con analogia a sindrome metabólico

Fruit purees can be added to diet as alternative sources of bioactive compounds for the prevention and/or improvement of the complications of metabolic syndrome. In this work we evaluated the effect of the intake of low-fat diets enriched with fruit purees (guava-strawberry, guava-blackberry, guava-soursop, guava-passion fruit) on the body weight and biochemical markers in metabolic syndrome analogy (MSA)-induced rats. The rats (n=6 for each treatment) were induced with a high fat diet and were injected with streptozotocin, one dose every week for 4 consecutive weeks after fasting overnight, then healthy rats were fed with standard diet and MS rats were fed with standard diet plus each of the fruit puree, for 4 weeks. As novel findings, the diet enriched with fruit purees was associated with a reduction in body weight (~13-21 %) and a control in the metabolism of glucose by decreasing plasma glucose (~5963 %). Also, there was a reduction in the total cholesterol, triacylglycerols, low-density lipoproteins, and low enzymatic activities of alanine aminotransferase, alkaline phosphatase and γ-glutamyl transferase, useful metabolites in the control of inflammatory processes in the liver. A notable improvement in the liver morphology was observed indicating that the treatments had a hepatoprotective effect. The diet enriched with guava-blackberry puree caused the best results on most biochemical markers of MS rats. Therefore, diets enriched with fruit purees can be an alternative for MS individuals for the control and improvement of the complications caused by this syndrome.

Los purés de frutas se pueden agregar a la dieta como fuentes alternativas de compuestos bioactivos para la prevención y / o mejora de las complicaciones del síndrome metabólico. En este trabajo evaluamos el efecto de la ingesta de dietas bajas en grasas, enriquecidas con purés de frutas (guayaba-fresa, guayaba-mora, guayaba-guanábana, guayaba-maracuyá) sobre el peso corporal y los marcadores bioquímicos en el síndrome metabólico (SM) inducido en ratas. Las ratas (n = 6 para cada tratamiento) fueron inducidas con una dieta alta en grasas y se les inyectó estreptozotocina, una dosis cada semana durante 4 semanas consecutivas después de ayunar durante la noche. Luego, las ratas sanas fueron alimentadas con una dieta estándar; y las ratas con SM fueron alimentadas con dieta estándar más cada uno de los purés de frutas, durante 4 semanas. Como hallazgos novedosos, la dieta enriquecida con purés de frutas se asoció con una reducción en el peso corporal (~ 13-21 %) y un control en el metabolismo de la glucosa al disminuir la glucosa en plasma (~ 59-63 %). Además, hubo una reducción en el colesterol total, triacilgliceroles, lipoproteínas de baja densidad, y bajas actividades enzimáticas de alanina aminotransferasa, fosfatasa alcalina y gama-glutamil transferasa, metabolitos útiles en el control de los procesos inflamatorios en el hígado. Se observó una mejora notable en la morfología del hígado, lo que indica que los tratamientos tuvieron un efecto hepatoprotector. La dieta enriquecida con puré de guayaba y mora causó los mejores resultados en la mayoría de los marcadores bioquímicos de las ratas con SM. Por lo tanto, las dietas enriquecidas con purés de frutas pueden ser una alternativa para las personas con SM, para el control y la mejora de las complicaciones causadas por este síndrome.

Selective loss of phosphoserine aminotransferase 1 (PSAT1) suppresses migration, invasion, and experimental metastasis in triple negative breast cancer.

Breast cancer is the second leading cause of cancer-related deaths among women and 90% of these mortalities can be attributed to progression to metastatic disease. In particular, triple negative breast cancer (TNBC) is extremely aggressive and frequently metastasizes to multiple organs. As TNBCs are categorized by their lack of hormone receptors, these tumors are very heterogeneous and are immune to most targeted therapies. Metabolic changes are observed in the majority of TNBC and a large proportion upregulate enzymes within the serine synthesis pathway, including phosphoserine aminotransferase 1 (PSAT1). In this report, we investigate the role of PSAT1 in migration and invasion potential in a subset of TNBC cell types. We found that the expression of PSAT1 increases with TNBC clinical grade. We also demonstrate that suppression of PSAT1 or phosphoglycerate dehydrogenase (PHGDH) does not negatively impact cell proliferation in TNBC cells that are not dependent on de novo serine synthesis. However, we observed that suppression of PSAT1 specifically alters the F-actin cytoskeletal arrangement and morphology in these TNBC cell lines. In addition, suppression of PSAT1 inhibits motility and migration in these TNBC cell lines, which is not recapitulated upon loss of PHGDH. PSAT1 silencing also reduced the number of lung tumor nodules in a model of experimental metastasis; yet did not decrease anchorage-independent growth. Together, these results suggest that PSAT1 functions to drive migratory potential in promoting metastasis in select TNBC cells independent of its role in serine synthesis.

Determining transaminase activity in bacterial libraries by time-lapse imaging.

Transaminase activity was determined by time-lapse imaging using a colourimetric reaction and image analysis. A correlation between the benzaldehyde conversion and relative luminance was determined, allowing the identification of the most promising biocatalysts, the determination of kinetic parameters, and the assessment of the effect of the substrate concentration on activity.

Hepatocarcinoma sobre hígado ectópico peritoneal / Ectopic hepatocellular carcinoma arising from the peritoneum

El hepatocarcinoma (HCC) sobre hígado ectópico es una entidad rara. La mayoría de los casos son asintomáticos y se descubren de manera casual en una autopsia o laparoscopia. En ocasiones producen clínica como dolor abdominal o hemorragia intraabdominal. Se realiza revisión de la literatura y se presenta el caso de una mujer de 68 años diagnosticada de hepatocarcinoma sobre hígado ectópico peritoneal a raíz de un estudio por hipertransaminasemia leve asintomática

Ectopic hepatocellular carcinoma is a rare entity. Most cases are asymptomatic and are occasionally found during autopsy or laparoscopy. They may sometimes cause relevant clinical problems such as abdominal pain or intra-abdominal bleeding. In this clinical case report, we review the literature in order to decipher the case of a 68-year-old female with an ectopic hepatocellular carcinoma that arose from the peritoneum. The patient was diagnosed after being studied due to a mild asymptomatic hypertransaminasemia