Elevated AST Levels Research Articles

Serum liver enzymes and diabetes from the Rafsanjan cohort study

BackgroundWe evaluated the relation between ALT, AST, GGT and ALP with diabetes in the Rafsanjan Cohort Study.Materials and methodsThe present study is a cross-sectional research including 9991 adults participated via sampling. We used data obtained from the Rafsanjan Cohort Study (RCS), as a part of the prospective epidemiological research studies in IrAN (PERSIAN). Elevated serum levels of ALT, AST, GGT and ALP were defined according to the reference range of the laboratory in the cohort center. Serum liver enzymes levels within the normal range were categorized into quartiles, and their relationship with diabetes was evaluated by logistic regressions.FindingsIn present study, elevated serum levels of ALT, AST, GGT, and ALP were associated with increased odds of diabetes (adjusted ORs: 1.81, 95%CI 1.51–2.17; 1.75, 95%CI 1.32–2.32; 1.77, 95%CI 1.50–2.08; 1.60, 95%CI 1.35–1.90 respectively). Also, in subjects with normal levels of ALT, GGT and ALP, a dose–response increase was shown for diabetes.ConclusionElevated levels of ALT, AST, GGT and ALP are related to a higher odds of diabetes. Also, increased levels of ALT, GGT and ALP even within normal range were independently related with the increased odds of diabetes. These results indicated the potential of elevated liver enzymes as biomarkers for the possible presence of diabetes.

Transient abnormal myelopoiesis in Down syndrome: Experience of long term follow up from a single tertiary center in Thailand

Transient abnormal myelopoiesis (TAM) is a unique disease occurring in Down syndrome (DS) infants from which most patients have spontaneous remission. This study aimed to evaluate the incidence and outcomes of TAM in a tertiary center in Thailand. We reviewed the records of 997 DS patients diagnosed between June 1993 and October 2019. From the 997 DS patients, 32 had been diagnosed with TAM. The incidence of TAM was 3.2% and an overall survival rate of 87.5%. A total of 2/28 who survived (7.1%) subsequently developed AML-DS at the ages of 2.1 and 4.5 years, respectively. The risk factors related with death included maternal multiparity, sepsis, skin bleeding, subcutaneous nodules, high WBC count, low hemoglobin, and elevated AST level. Abbreviations

Pirfenidone attenuates cardiac hypertrophy against isoproterenol by inhibiting activation of the janus tyrosine kinase-2/signal transducer and activator of transcription 3 (JAK-2/STAT3) signaling pathway

ABSTRACT Cardiovascular risk factors have attracted increasing attention in recent years with the acceleration of population aging, amongst which cardiac hypertrophy is the initiating link to heart failure. Pirfenidone is a promising agent for the treatment of idiopathic pulmonary fibrosis and has recently proven to exert inhibitory effects on the inflammatory response. This study proposes to explore the potential pharmacological action of pirfenidone in treating cardiac hypertrophy in a rodent model. Four groups of mice were used in the present study: the control, ISO (5 mg/kg/day) for 7 days, pirfenidone (200 mg/kg/day) for 14 days, and spironolactone (SPI) (200 mg/kg/day) for 14 days groups. Increased heart weight index, left ventricle (LV) weight index, LV wall thickness, declined LV volume, and elevated serum levels of CK-MB, AST, and LDH were observed in ISO-challenged mice, all of which were dramatically reversed by the administration of pirfenidone or SPI. Furthermore, an elevated cross-sectional area of cardiomyocytes in the wheat germ agglutinin (WGA) staining of heart cross-sections, upregulated atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), β-Myosin Heavy Chain (β-MHC), and excessively released tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in cardiac tissues were observed in the ISO group but greatly alleviated by pirfenidone or SPI. Lastly, the promoted expression levels of p-JAK-2/JAK-2 and p-STAT3/STAT-3 in the cardiac tissues of ISO-challenged mice were significantly repressed by pirfenidone or SPI. Collectively, our data reveals a therapeutic property of pirfenidone on ISO-induced cardiac hypertrophy in mice.

Loss of hepatic mTORC1 signaling affects liver homeostasis which is partially compensated by Wnt/β‐catenin pathway activation

BackgroundsLiver has an innate capacity to regenerate following partial hepatectomy (PH). Pathways including the mTORC1 and the Wnt/β‐catenin pathways have been shown to become activated after PH to enable liver regeneration (LR). However, how one pathway could compensate during deficiency of another is less well understood. Here, we report discovery and characterization of a compensatory interplay between mTOR and Wnt signaling that enables LR following PH when mTORC1 pathway is interrupted genetically.MethodsWe generated hepatocyte‐specific Raptor knockout (Raptor∆HC) mice by delivering AAV8‐TBG‐Cre to 6‐week‐old Raptorflox/flox mice. Two weeks after AAV8 injection, animals were either harvested at baseline, or subjected to partial hepatectomy (PH) for analysis to address changes and compensations during the process of LR.ResultsAcute deletion of hepatocyte Raptor abolished mTORC1 activity and led to compensatory activation of mTORC2 and its downstream target p‐AKT (S473). Raptor∆HC mice had baseline liver injury as shown by elevated serum levels of ALT, AST, and ALP. Raptor∆HC mice exhibited decreased levels of pericentral enzyme (Glul, Cyp2e1), periportal enzyme (G6pc), and main secretory proteins (Alb, Trf, Ttr), suggesting global impairment of metabolic, synthetic, and secretory functions. These mice were also under metabolic stress as seen by ER whorl formation, mitochondrial swelling, and increased autophagy, by transmission electron microscopy (TEM). There was an increase in cell death seen as enhanced apoptotic body formation by TUNEL and cleaved caspase‐3 staining and an associated increase in macrophage infiltration in the immediate proximity of dying hepatocytes. An attempt at compensatory liver regeneration was concurrently evident through activation of the Wnt/β‐catenin pathway leading to enhanced Cyclin D1, Ki67, Axin2 and c‐Myc. β‐Catenin protein increased 5‐fold in Raptor∆HC mice and appears to be due to both increased gene transcription and decreased phosphorylation‐mediated degradation. Further, stabilization of β‐catenin protein appears to be due to both cell‐extrinsic mechanism seen as increased p‐LPR6 (S1490) suggesting Wnt stimulation, and cell‐intrinsic mechanism seen as decreased GSK3β activity which was phosphorylated and inhibited by compensatory elevation of AKT activity in the Raptor∆HC mice. Despite activation of the Wnt pathways, hepatocytes failed to finish cell cycle seen as an overall decrease in BrdU incorporation after a 14‐day continuous pulse. Indeed, when Raptor∆HC mice were subjected to PH, they all died within 48h.ConclusionsmTORC1 activity is essential for homeostatic liver functions and for LR after PH. Stabilization of β‐catenin due to multiple mechanisms including Wnt secretion likely from macrophages, secondary to AKT mediated GSK3β inhibition and via de novo β‐catenin transcription, attempts to compensate to maintain homeostasis in the Raptor∆HC mice.

The Protective Role of IL-36/IL-36R Signal in Con A-Induced Acute Hepatitis

Abstract The IL-36 family, including IL-36α, IL-36β, IL-36γ, and IL-36 receptor antagonist (IL-36Ra), belongs to the IL-1 super-family. Although IL-36 is known to play a role in autoimmune diseases, it remains unclear as how IL-36 regulates inflammation in the liver. To determine the role of IL-36/IL-36R signaling pathways, we established an acute hepatitis mouse model by intravenous injection of the plant lectin concanavalin A (Con A), and found that the levels of IL-36 were increased in the liver following Con A injection. We also demonstrated that intrahepatic leukocytes, but not hepatocytes, were the main source of IL-36. Moreover, further research verified that infiltrated neutrophils were the main source of IL-36γ in the liver. Using the IL-36R knockout mouse model (H-2b), surprisingly, we found that the absence of IL-36 signals led to aggravated liver injuries, as evidenced by increased mortality, accompanied by elevated serum ALT and AST levels and severe pathological changes in the liver. Further investigations demonstrated that a lack of IL-36 signaling induced intrahepatic activation of CD4+ and CD8+T lymphocytes and increased the production of inflammatory cytokines. In addition, IL-36R knockout mice had reduced Treg cell functions and chemotaxis in the liver. Together, our results suggest a vital role of IL-36 in regulating T cell function and homeostasis during liver injury and inflammation. Supported by grants from NIH (R01 EY028773, AI132674, R21 AI153586)

Hepatoprotective effects of flexirubin, a novel pigment from Chryseobacterium artocarpi, against carbon tetrachloride-induced liver injury: An in vivo study and molecular modeling

Liver injuries caused by various industrial chemicals represent a serious health concern worldwide. Flexirubins are a novel class of naturally occurring bacterial pigments whose bioactivity remains largely unexplored. The present study evaluated the hepatoprotective effects of flexirubin pigment extracted from the bacterium Chryseobacterium artocarpi against CCl4-induced acute liver injury in mice. Flexirubin was applied at three different oral doses, 125, 250 and 500 mg/kg bw/d for seven consecutive days. Treatment of animals with flexirubin before exposure to CCl4 (10 mL/kg bw dissolved in olive oil, 1:1 v/v) significantly decreased the elevated serum levels of ALT, AST, ALP, LDH and TBL. Flexirubin pretreatment showed a great capability for attenuating the CCl4-induced oxidative stress by decreasing the level of liver MDA, and increasing the antioxidant enzyme activities of liver SOD and CAT, and the levels of GSH and TAC. Flexirubin also alleviated the histopathological alterations in liver by prohibiting steatosis, ballooning degeneration, leukocytic infiltration and necrosis. Immunohistochemical analysis demonstrated that flexirubin has a significant anti-apoptotic activity against CCl4 via upregulation of Bcl-2, and downregulation of Bax, Caspase-3 and TGF-β1. Flexirubin also exhibited a remarkable anti-inflammatory activity against CCl4 through its suppressive action on TNF-α, COX-2 and CD-45. Flexirubin could trigger upregulation of the Nrf2/HO-1 signaling pathway mediating protection against CCl4. In silico molecular docking revealed flexirubin as a potential inhibitor against two target proteins, TGF-β1 and TACE. The results proved the effectiveness of flexirubin as a significant source of natural compounds for its use in drug formulation strategies to offer protection against hepatotoxins.

12-Month Post-Discharge Liver Function Test Abnormalities Among Patients With COVID-19: A Single-Center Prospective Cohort Study.

ObjectiveThe longitudinal effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the liver are unknown. This study aimed to characterize dynamic changes in liver function test abnormalities in patients with COVID-19 at the acute phase and recovery phase.MethodsA prospective cohort study involved patients with COVID-19 who were admitted to Shenzhen Third People’s Hospital between January 11, 2020, and April 27, 2020. Patients underwent liver function tests at hospitalization and at the outpatient visit at the 1-month, 3-month, 6-month, and 12-month follow-ups.ResultsAmong 461 patients, 28.4% of patients had any kind of liver function tests abnormality at admission, manifested as elevated ALT (13.0%), AST (17.6%), and GGT (15.8%) levels. The trajectory analysis indicated a marked improvement in liver function after discharge, with any kind of liver function test abnormalities of 25.1% at 1 month, 13.2% at 3 months, 16.7% at 6 months, and 13.2% at 12 months after discharge. Persistent liver function abnormalities were observed in patients with pre-existing conditions during follow-up. A significantly higher prevalence of ultrasound determined fatty liver disease was found in those patients with more frequent LFT abnormalities at follow-up.ConclusionIn this study of patients with COVID-19, liver damage in COVID-19 was usually temporary and could return to normal at the end of the 12-month follow-up.

Liver pathology and biochemistry in patients with mutations in TRIM37 gene (Mulibrey nanism).

Background and AimsMulibrey nanism (MUL) is a multiorgan disease caused by recessive mutations in the TRIM37 gene. Chronic heart failure and hepatopathy are major determinants of prognosis in MUL patients, which prompted us to study liver biochemistry and pathology in a national cohort of MUL patients.MethodsClinical, laboratory and imaging data were collected in a cross‐sectional survey and retrospectively from hospital records. Liver histology and immunohistochemistry for 10 biomarkers were assessed.ResultsTwenty‐one MUL patients (age 1–51 years) with tumour suspicion showed moderate congestion, steatosis and fibrosis in liver biopsies and marginally elevated levels of serum GGT, AST, ALT and AST to platelet ratio index (APRI) in 20%–66%. Similarly, GGT, AST, ALT and APRI levels were moderately elevated in 12%–69% of 17 MUL patients prior to pericardiectomy. In a cross‐sectional evaluation of 36 MUL outpatients, GGT, total bilirubin and galactose half‐life (Gal½) correlated with age (r = 0.45, p = .017; r = 0.512, p = .007; r = 0.44, p = .03 respectively). The frequency of clearly abnormal serum values of 15 parameters analysed, however, was low even in patients with signs of restrictive cardiomyopathy. Transient elastography (TE) of the liver revealed elevated levels in 50% of patients with signs of heart failure and TE levels correlated with several biochemistry parameters. Biomarkers of fibrosis, sinusoidal capillarization and hepatocyte metaplasia showed increased expression in autopsy liver samples from 15 MUL patients.ConclusionLiver disease in MUL patients was characterized by sinusoidal dilatation, steatosis and fibrosis with individual progression to cirrhosis and moderate association of histology with cardiac function, liver biochemistry and elastography.

Hematobiochemical variability and predictors of new-onset and persistent postpartum preeclampsia

Preeclampsia (PE) can occur antepartum or postpartum. When it develops de novo after childbirth, it is termed new-onset postpartum PE (NOPPE). Often, antepartum PE disappears after childbirth; however, in some women it persists after childbirth. This form of PE is termed persistent PE (PPE). Thus, there are two forms of postpartum PE: NOPPE and PPE. The pathogenesis and pathophysiology of these diseases have not been fully characterized, and whether NOPPE and PPE are different or similar pathological conditions remains unexplored. Thus, we aimed to compare the haematological and biochemical characteristics of NOPPE and PPE, predict the occurrence of new-onset PE and identify lifestyles that predispose women to postpartum PE. A total of 130 women comprising 65 normotensive postpartum women, 33 NOPPE and 32 PPE women were recruited for this hospital-based case–control study. The socio-demographic and lifestyle characteristics of the participants were obtained through well-structured questionnaires. Haematological and biochemical indices were measured using automated analysers and ELISA. The prevalence of postpartum PE was 11.9%. Dyslipidaemia (p = < 0.0001), hypomagnesaemia (p = < 0.001), elevated serum levels of ALT, AST (p = < 0.0001), sVCAM-1 (p = < 0.0001) and sFlt-1 (p = < 0.0001) were more prevalent and severe in the PPE than in the NOPPE. Sedentary lifestyle was common among both groups of hypertensive women. Elevated ALT and AST were significant predictors of NOPPE. These findings indicate that preeclampsia exists after childbirth in a high percentage of women. NOPPE and PPE are different pathological conditions that require different clinical management. Combined glucose, lipid and liver assessment could be useful in predicting postpartum PE.

Pneumatosis intestinalis in abdominal CT: predictors of short-term mortality in patients with clinical suspicion of mesenteric ischemia

PurposePneumatosis intestinalis (PI) in the bowel wall demonstrated in computed tomography (CT) of the abdomen is unspecific and its prognostic relevance remains poorly understood. The purpose of this study was to identify predictors of short-term mortality in patients with suspected mesenteric ischemia who were referred to abdominal CT and showed PI.MethodsIn this retrospective, IRB-approved, single-centre study, CT scans and electronic medical records of 540 patients who were referred to abdominal CT with clinical suspicion of mesenteric ischemia were analysed. 109/540 (20%) patients (median age 66 years, 39 females) showed PI. CT findings were correlated with surgical and pathology reports (if available), with clinical and laboratory findings, and with patient history. Short-term outcome was defined as survival within 30 days after CT.ResultsPI was found in the stomach (n = 6), small bowel (n = 65), and colon (n = 85). Further gas was found in mesenteric (n = 54), portal (n = 19) and intrahepatic veins (n = 36). Multivariate analysis revealed that PI in the colon [odds ratio (OR) 2.86], elevated blood AST levels (OR 3.00), and presence of perfusion inhomogeneities in other abdominal organs (OR 3.38) were independent predictors of short-term mortality. Surgery had a positive effect on mortality (88% lower likelihood of mortality), similar to the presence of abdominal pain (65% lower likelihood).ConclusionsOur study suggests that in patients referred for abdominal CT with clinical suspicion of mesenteric ischemia, location of PI in the colon, elevation of blood AST, and presence of perfusion inhomogeneities in parenchymatous organs are predictors of short-term mortality.Graphical abstract

STUDY OF ACUTE HEPATIC DYSFUNCTION ASSOCIATED WITH DENGUE FEVER IN NORTH WEST ZONE OF RAJASTHAN

Background: Atypical manifestations of dengue viral fever have been described in recent past, including involvement of the central nervous system, cardiac alterations, and elevations in aminotransferase levels, with reactive hepatitis. Hepatic involvement can be characterized by manifestations of acute hepatitis, with pain in the right hypochondrium, hepatomegaly, jaundice, and raised aminotransferase levels. Although the liver is not the directly targeted organ for dengue virus, histopathological findings, including centrilobular necrosis, fatty alterations, hyperplasia of the Kupffer cells, acidophil bodies and monocyte infiltration of the portal tract have been detected in patients with dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS). In most cases, hepatic involvement prolongs the clinical course of this self-limiting viral infection, but it does not constitute a sign of worse prognosis.&#x0D; Methods: Hundred confirmed diagnosed inpatient cases of dengue fever were included. Clinical examination and laboratory investigations including liver function tests and serum electrolyte levels were performed regularly at appropriate interval. Viral hepatitis testing was also performed to check for any co-infection or pre-existing viral hepatitis. On the basis of increase in serum aminotransferase levels, patients were divided into two groups; Mild (up to 5 times normal) to Moderate (5- 10 times) acute hepatitis: AST or ALT 45-300 IU/L and severe acute hepatitis: AST or ALT &gt; 300 IU/L or ? 10 times. On basis of serum protein levels, the patients were grouped in two groups, one with hypoalbuminemia; serum albumin &lt;3.0 g/dL and without hypoalbuminemia&#x0D; Results: In this study out of total 100 patients 67 were men (67%) and 33 were women (33%). The mean age of the patients was 39 ± 3.1 years. The patients were in the range of age 22-54 years. Maximum number of patients were in third decade of life. All the patients were tested positive for NS1 antigen test. Fever was the most common presenting complaint with mean duration of fever was 6 ± 3.27 days with mean temperature of 38.5 ± 1°C, 21% had abdominal pain, 17% had rash, 3% had jaundice. Liver function tests (LFTs) show the median ALT of 88.50 IU/L with range from 43.25-317.22 IU/L, median AST of 174 IU/L with range from 47-371.5 IU/L. 91% of the patients had elevated AST levels and almost 79% patients had elevated ALT (hepatitis). Normal levels of serum aminotransferase AST and ALT levels were seen in 9% and 21% patients respectively. Mild to moderate increase in AST and ALT levels were seen in 84% and 75% of cases respectively whereas more than 10-fold increase in AST and ALT levels were seen in 7% and 4% patients respectively as shown in Table 1. Mortality was 2% in our study.&#x0D; Conclusions: Dengue viral fever contributes significantly to the disease burden in developing countries. Although the disease is self-limiting, but a significant number of cases show signs of organ dysfunction including liver dysfunction. The diagnosis of Dengue may be difficult in some cases due to false negative reports in first few days. It is thus important to investigate all suspected dengue patients with liver function test (serum transaminases levels), so that liver dysfunction can be detected early and proper management can be initiated.&#x0D; Keywords: Dengue Viral Fever, Immune Hepatitis, Serum Aminotransferases, Hepatic Dysfunction.

Clinical Characteristics and Predictors of Mortality in Obese African-Americans with COVID-19: a Single-Center Retrospective Study.

Background This study aims to add to the body of evidence linking obesity as an established risk factor for COVID-19 infection and also look at predictors of mortality for COVID-19 in the African-Americans (AA) population.MethodsA retrospective cohort study of patients with confirmed COVID-19 infection was done in a community hospital in New York City. The cohort was divided into two groups, with the non-obese group having a BMI < 30 kg/m2 and the obese group with a BMI ≥ 30 kg/m2. Clinical predictors of mortality were assessed using multivariate regression analysis.ResultsAmong the 469 (AA) patients included in the study, 56.3% (n = 264) had a BMI < 30 kg/m2 and 43.7% (n = 205) had a BMI ≥ 30 kg/m2. Most common comorbidities were hypertension (n = 304, 64.8%), diabetes (n = 200, 42.6%), and dyslipidemia (n = 74, 15.8%). Cough, fever/chills, and shortness of breath had a higher percentage of occurring in the obese group (67.8 vs. 55.7%, p = 0.008; 58.0 vs. 46.2%, p = 0.011; 72.2 vs. 59.8%, p = 0.005, respectively). In-hospital mortality (41.5 vs. 25.4%, p < 0.001) and mechanical ventilation rates (34.6 vs. 22.7%, p = 0.004) were also greater for the obese group. Advanced age (p = 0.034), elevated sodium levels (p = 0.04), and elevated levels of AST (0.012) were associated with an increase in likelihood of in-hospital mortality in obese group.ConclusionsOur results show that having a BMI that is ≥ 30 kg/m2 is a significant risk factor in COVID-19 morbidity and mortality. These results highlight the need for caution when managing obese individuals.

Impact of Intravenous Trehalose Administration in Patients with Niemann-Pick Disease Types A and B.

Background and Aims: Niemann–Pick disease (NPD) types A (NPA) and B (NPB) are caused by deficiency of the acid sphingomyelinase enzyme, which is encoded by the SMPD1 gene, resulting in progressive pathogenic accumulation of lipids in tissues. Trehalose has been suggested as an autophagy inducer with therapeutic neuroprotective effects. We performed a single-arm, open-label pilot study to assess the potential efficacy of trehalose treatment in patients with NPA and NPB patients. Methods: Five patients with NPD type A and B were enrolled in an open-label, single-arm clinical trial. Trehalose was administrated intravenously (IV) (15 g/week) for three months. The efficacy of trehalose in the management of clinical symptoms was evaluated in patients by assessing the quality of life, serum biomarkers, and high-resolution computed tomography (HRCT) of the lungs at the baseline and end of the interventional trial (day 0 and week 12). Results: The mean of TNO-AZL Preschool children Quality of Life (TAPQOL) scores increased in all patients after intervention at W12 compared to the baseline W0, although the difference was not statistically significant. The serum levels of lyso-SM-509 and lyso-SM were decreased in three and four patients out of five, respectively, compared with baseline. Elevated ALT and AST levels were decreased in all patients after 12 weeks of treatment; however, changes were not statistically significant. Pro-oxidant antioxidant balance (PAB) was also decreased and glutathione peroxidase (GPX) activity was increased in serum of patients at the end of the study. Imaging studies of spleen and lung HRCT showed improvement of symptoms in two patients. Conclusions: Positive trends in health-related quality of life (HRQoL), serum biomarkers, and organomegaly were observed after 3 months of treatment with trehalose in patients with NPA and NPB. Although not statistically significant, due to the small number of patients enrolled, these results are encouraging and should be further explored.

Течение и лечебные подходы при неалкогольной жировой болезни печени у лиц с сахарным диабетом 2 типа

Non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (DM2) are often combined and often burden each other. The purpose was to compare demographic, clinical, laboratory and ultrasound characteristics of patients with NAFLD and the presence or absence of type 2 diabetes mellitus during prospective follow-up. Material and methods. 56 patients with NAFLD (18 men and 37 women) aged 57.7 (6.2) years were under observation. Patients were divided into 2 groups: group 1 (31 patients with NAFLD and DM2) and group 2 (32 patients with NAFLD without DM2). General clinical and biochemical blood tests and ultrasound examinations of the liver were performed at baseline and after 6 and 12 months of follow-up in all patients (ultrasound device Aplio 500 (TOSHIBA, Japan). The liver structure was evaluated using the recommendations of R.V. Eifler (2013); S. Saadeh (2002). The program MedStat 4.0 was used for statistical processing of the material. Results. Overweight, arterial hypertension, coronary heart disease, dyslipidemia, hyperuricemia, elevated levels of AST and ALT were detected in group 1 more often than in group 2 (p &lt; 0.05). There were no significant differences between the groups in the frequency and severity of clinical manifestations of NAFLD, in the average values of alkaline phosphatase and GGT concentrations (all p &gt; 0.05). There was a statistically significant relationship between the increase in aminotransferase levels by 2 or more times and the glycosylated hemoglobin levels (χ2 = 8.53, p &lt; 0.01), the DM2 duration (χ2 = 6.71, p &lt; 0.05), the presence of retinopathy and/or nephropathy (χ2 = 5.92, p &lt; 0.05). Among the patients of the group 1, the ultrasound examination significantly more often revealed an increased liver echogenicity, multiple drain hyperechoic changes and its diffuse lesion (all p &lt; 0.05). Conclusions. NAFLD in patients with DM2 has a number of clinical, laboratory and ultrasound features compared with patients with NAFLD without diabetes.

Corchorus olitorius L. Leaf Extract Protects Rats from Acrylamide-Induced Hepatic Injury

Acrylamide is a water-soluble compound that forms during the high-temperature cooking of starchy foods and has carcinogenic, neurotoxic, and genotoxic properties. Also, short-term exposure to acrylamide has been shown to cause significant hepatic injury in laboratory animals, along with disruption of antioxidant defense mechanisms due to excessive ROS production. Therefore, dietary antioxidants are believed to be useful in combating the negative effects of acrylamide. Corchorus olitoris L., also known as molokhia in Arabic, is a leafy vegetable which is shown to possess potent antioxidant and organoprotective properties. In this study, rats were administered with an aqueous extract of molokhia leaves to see if it could protect them against acrylamide-induced hepatic damage. Hepatic injury markers included serum total protein, total bilirubin, ALT, AST, and ALP, while oxidative stress markers included MDA, GSH, CAT, and SOD after dosing with three levels of extract (100, 250, and 500 mg/kg) for 21 days. Results indicated that the extracts substantially reduced elevated levels of bilirubin, ALT, AST, ALP, and MDA to normal levels at all doses. The extracts also brought serum protein, GSH, CAT, and SOD levels back to normal. Although the restoration of serum hepatic enzyme levels was dose dependent, no specific dose dependent relationship was found for serum proteins, MDA, GSH, CAT, or SOD activities. The study's findings show that molokhia leaves extract protects against acrylamide-induced hepatic damage by virtue of its good radical scavenging and anti-lipiperoxidative properties conferred by phenolics, flavonoids, and alkaloids.

Mitigation of doxorubicin-induced cardiotoxicity by dichloroacetate: potential roles of restoration of PGC-1α/SIRT3 signaling and suppression of oxidative stress and apoptosis.

Doxorubicin (DOX) is an effective chemotherapeutic agent used in the treatment of various neoplasms. Nevertheless, its therapeutic efficacy is hampered by life-threatening heart failure. Therefore, the current study was undertaken to investigate whether dichloroacetate (DCA), a metabolic and mitochondrial modulator, when administered at a therapeutically feasible dose could potentially reverse acute DOX cardiotoxicity. Furthermore, the possible underlying mechanisms of cardioprotection were also assessed. Different techniques were performed to assess cardiac injury like echocardiography, histopathology, transmission electron microscope, biomarkers of cardiac injury, and oxidative stress markers. Further, the expression levels of mRNA and protein were quantified by PCR and immunohistochemistry, respectively. Echocardiography showed that mice that received DOX/DCA combination were protected against heart failure. Additionally, histopathology and transmission electron microscopy revealed structural damage alleviation by DOX/DCA combination, which was confirmed biochemically via significant suppression of elevated CK-MB and AST levels. Mechanistically, DOX dysregulated the expression of PGC-1α and SIRT-3 genes which are key to normal mitochondrial functioning. Of note, co-treatment with DCA effectively restored PGC-1α/SIRT-3 signaling and normalized the mitochondrial DNA index. Moreover, events downstream of DOX-triggered mitochondrial dysfunction such as oxidative stress and p53-dependent apoptosis were all abrogated by combination with DCA. The present study is the first to provide in vivo evidence that DCA is effective in protecting against acute DOX cardiotoxicity. Additionally, the study highlights the potential of administering metabolic modulators to safeguard against DOX cardiotoxicity.

Development of herpetrione nanosuspensions stabilized by glycyrrhizin for enhancing bioavailability and synergistic hepatoprotective effect

The objective of this study was to develop novel herpetrione (HPE) nanosuspensions stabilized by glycyrrhizin (HPE NSs/GL) for enhancing bioavailability and hepatoprotective effect of HPE. HPE NSs/GL were prepared by wet media milling method and then systemically evaluated by particle size analysis, scanning electronic microscopy (SEM), X-ray powder diffraction (XRPD), dissolution test, pharmacokinetics, and hepatoprotective effect. HPE-NSs stabilized by poloxamer 407 (HPE NSs/P407) were also prepared and used as a reference for comparison. HPE NSs/GL and HPE-NSs/P407 with similar particle sizes around 450 nm and PDI less than 0.2 were successfully prepared and both of them appeared to be spherical under SEM. The XRPD results demonstrated that HPE in both HPE NSs/GL and HPE NSs/P407 was presented in the amorphous state and the addition of GL or P407 and the milling process didn’t alter the physical state of HPE. The dissolution and pharmacokinetic studies demonstrated that HPE NSs/GL exhibited significant enhancement in drug dissolution (72.44% within 24 h) and AUC0–t (24.91 ± 3.3 mg/L·h) as compared to HPE coarse suspensions (HPE CS, 34.19% & 13.07 ± 1.02 mg/L·h), but was similar with those of HPE NSs/P407 (80.06% & 26.75 ± 4.06 mg/L•h). Moreover, HPE NSs/GL exhibited significantly better hepatoprotective effect as compared to HPE CS and HPE NSs/P407 as indicated by the lowering of the elevated serum ALT and AST levels and the improvement of the hepatic morphology and architecture, which might be attributed to the improved bioavailability of HPE, and synergistic hepatoprotective effect of GL via alleviating inflammation evidenced by the significant decreased hepatic levels of inflammatory cytokines IL-1β, IL-6 and TNF-α. It could be concluded that GL might be an effective stabilizer for preparing HPE NSs, and HPE NSs/GL is a potential formulation strategy for improving oral bioavailability and hepatoprotective effect of HPE.

Association between serum alanine and aspartate aminotransferase and blood pressure: a cross-sectional study of Chinese freshmen

BackgroundHigh blood pressure is a well-recognized risk factor for cardiovascular events, and the incidence of hypertension is increasing among young people. This study investigated the relationship between ALT and AST levels and hypertension among freshmen in China.MethodsThis cross-sectional study was conducted in the Anhui Province from September to November 2018. A total of 3114 freshmen underwent a physical examination including testing of biochemical indicators and a standardized questionnaire.ResultsThe overall prevalence of elevated ALT and AST were 6.8% and 2.3% among freshmen. The mean ALT and AST levels were higher in males (22.59 ± 21.98 vs.12.62 ± 10.30 U/L; 23.55 ± 12.24 vs. 20.02 ± 5.75 U/L, respectively). The prevalence of hypertension was significantly higher in men (16.1%) than in women (1.9%). The mean values of BMI, SBP, DBP, TC, TG, and LDL-C were found to be increased with elevated levels of serum ALT and AST in the quartiles (P for trend < 0.05). After adjusting for covariates, the risk of hypertension was significantly higher in the highest ALT quartile than in the lowest quartile (OR (95% CI) of 1.681 (1.028, 2.751) in males; 2.802 (1.102, 7.124) in females). A strong linear relationship was found between serum ALT levels and the odds of hypertension after adjustment for potential confounders only in total population and females (P for trend < 0.05).ConclusionsThese findings suggest that ALT level is significantly associated with hypertension both in male and female freshmen.

A homozygous R148W mutation in Semaphorin 7A causes progressive familial intrahepatic cholestasis

Semaphorin 7A (SEMA7A) is a membrane‐bound protein that involves axon growth and other biological processes. SEMA7A mutations are associated with vertebral fracture and Kallmann syndrome. Here, we report a case with a mutation in SEMA7A that displays familial cholestasis. WGS reveals a SEMA7AR148W homozygous mutation in a female child with elevated levels of serum ALT, AST, and total bile acid (TBA) of unknown etiology. This patient also carried a SLC10A1S267F allele, but Slc10a1S267F homozygous mice exhibited normal liver function. Similar to the child, Sema7aR145W homozygous mice displayed elevated levels of serum ALT, AST, and TBA. Remarkably, liver histology and LC‐MS/MS analyses exhibited hepatocyte hydropic degeneration and increased liver bile acid (BA) levels in Sema7aR145W homozygous mice. Further mechanistic studies demonstrated that Sema7aR145W mutation reduced the expression of canalicular membrane BA transporters, bile salt export pump (Bsep), and multidrug resistance‐associated protein‐2 (Mrp2), causing intrahepatic cholestasis in mice. Administration with ursodeoxycholic acid and a dietary supplement glutathione improved liver function in the child. Therefore, Sema7aR145W homozygous mutation causes intrahepatic cholestasis by reducing hepatic Bsep and Mrp2 expression.

Predictors of severity and development of critical illness of Egyptian COVID-19 patients: A multicenter study.

We conducted the present multicenter, retrospective study to assess the epidemiological, clinical, laboratory, and radiological characteristics associated with critical illness among patients with COVID-19 from Egypt. The present study was a multicenter, retrospective study that retrieved the data of all Egyptian cases with confirmed COVID-19 admitted to hospitals affiliated to the General Organization for Teaching Hospitals and Institutes (GOTHI) through the period from March to July 2020. The diagnosis of COVID-19 was based on a positive reverse transcription-polymerase chain reaction (RT-PCR) laboratory test. This retrospective study included 2724 COVID-19 patients, of whom 423 (15.52%) were critically ill. Approximately 45.86% of the critical group aged above 60 years, compared to 39.59% in the non-critical group (p = 0.016). Multivariate analysis showed that many factors were predictors of critically illness, including age >60 years (OR = 1.30, 95% CI [1.05, 1.61], p = 0.014), low oxygen saturation (OR = 0.93, 95% CI [0.91, 0.95], p<0.001), low Glasgow coma scale (OR = 0.75, 95% CI [0.67, 0.84], p<0.001), diabetes (OR = 1.62, 95% CI [1.26, 2.08], p<0.001), cancer (OR = 2.47, 95% CI [1.41, 4.35], p = 0.002), and serum ferritin (OR = 1.004, 95% CI [1.0003, 1.008], p = 0.031). In the present report, we demonstrated that many factors are associated with COVID-19 critical illness, including older age groups, fatigue, elevated temperature, increased pulse, lower oxygen saturation, the preexistence of diabetes, malignancies, cardiovascular disease, renal diseases, and pulmonary disease. Moreover, elevated serum levels of ALT, AST, and ferritin are associated with worse outcomes. Further studies are required to identify independent predictors of mortality for patients with COVID-19.