Hypoalbuminemia as an unusual presentation of undiagnosed atypical celiac disease in an 84-year-old woman.

Celiac disease is a chronic, immune-mediated enteropathy that is precipitated by dietary gluten in genetically predisposed individuals. Classical form of the disease is characterized by gastrointestinal symptoms and signs of malabsorption, while patients with nonclassical celiac disease lack significant gastrointestinal symptoms. We report an uncommon case of celiac disease in an 84 -year-old oligosymptomatic female with a recently treated colon tumor, diagnosed during the investigation of profound hypoproteinemia and hypoalbuminemia.

Myocardial deposition of aluminum, arsenic, cadmium, and lead accelerates heart failure and alters UPRmt in humans.

In the myocardium of control subjects and patients undergoing heart transplantation or left ventricular assist device implantation (LVAD), we analyzed concentrations of Al, As, Cd, Pb, and Ni using inductively coupled plasma mass spectrometry. Myocardial generation of oxidative-stress-induced lipid peroxidation was analyzed by quantifying concentration of 4-Hydroxynonenal (4-HNE) with ELISA and pro-apoptotic DAPK2 gene expression was determined with quantitative RT-PCR. Compared to six control hearts, myocardial samples of 128 individuals undergoing heart transplantation or LVAD implantation exhibited a moderate increase in deposition of five tested non-essential elements, which was significantly increased only for Cd and cumulative deposition of Al, As, Cd, and Pb.

Cardiotoxicity of Iron and Zinc and Their Association with the Mitochondrial Unfolded Protein Response in Humans.

This study was designed to examine the association between myocardial concentrations of the trace elements Cu, Fe, Mn, Mo, and Zn and the expression of mitochondrial unfolded protein response (UPRmt) elements and the age of patients who received heart transplantation or a left-ventricular assist device (ageHTx/LVAD). Inductively coupled plasma mass spectrometry was used to determine the concentration of Cu, Fe, Mn, Mo, and Zn in the myocardium of control subjects and patients undergoing heart transplantation or left-ventricular assist device (LVAD) implantation. We used ELISA to quantify the expression of UPRmt proteins and 4-Hydroxynonenal (4-HNE), which served as a marker of oxidative-stress-induced lipid peroxidation.

Salivary Interleukin-13 and Transforming Growth Factor Beta as Potential Biomarkers of Cancer Cachexia.

Unlabelled: Cancer cachexia is a syndrome characterized by weight and muscle loss and functional impairment, strongly influencing survival in cancer patients. In this study, we aimed to establish the role of saliva cytokine measurement in cancer cachexia investigation and define two potential independent salivary biomarkers of the condition.

Methods: serum and saliva specimens were obtained from 78 patients.

A rare form of LIM domain-binding protein 3 (LDB3) mutation causes hypertrophic cardiomyopathy and myofibrillar myopathy type 4.

Polymorphisms in LDB3 gene can cause various forms of cardiomyopathy and myofibrillar myopathy 4 (MM4). Patient described in this study presented with a hypertrophic cardiomyopathy (HCM) and distal myopathy suggestive of myofibrillar myopathy 4. Genetic analysis using the TruSight Cardio Sequencing Kit (Illumina) revealed suspected LDB3 variant (c.

Predictors of prolonged hospitalization of COVID-19 patients.

Purpose: Despite the importance of hospital bed network during the pandemic, there are scarce data available regarding factors predictive of prolonged length of hospitalization of COVID-19 patients.

Methods: We retrospectively analyzed a total of 5959 consecutive hospitalized COVID-19 patients in period 3/2020-6/2021 from a single tertiary-level institution. Prolonged hospitalization was defined as hospital stay > 21 days to account for mandatory isolation period in immunocompromised patients.

Human C2a and C6a iPSC lines and H9 ESC line have less efficient cardiomyogenesis than H1 ESC line: Beating enhances cardiac differentiation.

Background: Human induced pluripotent stem cells (hiPSCs) need to be thoroughly characterized to exploit their potential advantages in various aspects of biomedicine. The aim of this study was to compare the efficiency of cardiomyogenesis of two hiPSCs and two human embryonic stem cell (hESC) lines by genetic living cardiomyocyte labeling. We also analyzed the influence of spontaneous beating on cardiac differentiation.

Prognostic value of circulating Bcl-2 and anti-p53 antibodies in patients with breast cancer: A long term follow-up (17.5 years).

Background: Apoptosis inhibition is a major tumorigenic factor. Bcl-2 dysregulation and TP53 mutation status, which may correlate with autoantibody generation, contribute to impaired apoptosis.

Objective: This study aimed to investigate the prognostic value of circulating Bcl-2 and anti-p53 antibodies (p53Abs) in a 17.

Mitochondrial ROS Induce Partial Dedifferentiation of Human Mesothelioma via Upregulation of NANOG.

The expression of pluripotency factors is a key regulator of tumor differentiation status and cancer stem cells. The purpose of this study was to examine the expression of pluripotency factors and differentiation status of human mesothelioma and the role of mitochondria in their regulation. We tested the expression of OCT4/, NANOG, SOX2, PI3K-AKT pathway and BCL2 genes and proteins in 65 samples of human mesothelioma and 19 samples of normal mesothelium.

Mitochondrial unfolded protein response, mitophagy and other mitochondrial quality control mechanisms in heart disease and aged heart.

Mitochondria are involved in crucial homeostatic processes in the cell: the production of adenosine triphosphate and reactive oxygen species, and the release of pro-apoptotic molecules. Thus, cell survival depends on the maintenance of proper mitochondrial function by mitochondrial quality control. The most important mitochondrial quality control mechanisms are mitochondrial unfolded protein response, mitophagy, biogenesis, and fusion-fission dynamics.

Differentiating Between Malignant Mesothelioma and Other Pleural Lesions Using Fourier Transform Infrared Spectroscopy.

Histopathology, despite being the gold standard as a diagnostic tool, does not always provide a correct diagnosis for different pleural lesions. Although great progress was made in this field, the problem to differentiate between reactive and malignant pleural lesions still stimulates the search for additional diagnostic tools. Our research using vibrational spectroscopy and principal component analysis (PCA) statistical modeling represents a potentially useful tool to approach the problem.

Non-linear actions of physiological agents: Finite disarrangements elicit fitness benefits.

Finite disarrangements of important (vital) physiological agents and nutrients can induce plethora of beneficial effects, exceeding mere attenuation of the specific stress. Such response to disrupted homeostasis appears to be universally conserved among species. The underlying mechanism of improved fitness and longevity, when physiological agents act outside their normal range is similar to hormesis, a phenomenon whereby toxins elicit beneficial effects at low doses.

Targeted Modification of Mitochondrial ROS Production Converts High Glucose-Induced Cytotoxicity to Cytoprotection: Effects on Anesthetic Preconditioning.

Contradictory reports on the effects of diabetes and hyperglycemia on myocardial infarction range from cytotoxicity to cytoprotection. The study was designed to investigate acute effects of high glucose-driven changes in mitochondrial metabolism and osmolarity on adaptive mechanisms and resistance to oxidative stress of isolated rat cardiomyocytes. We examined the effects of high glucose on several parameters of mitochondrial bioenergetics, including changes in oxygen consumption, mitochondrial membrane potential, and NAD(P)H fluorometry.

Cardioprotection during diabetes: the role of mitochondrial DNA.

Background: Diabetes alters mitochondrial bioenergetics and consequently disrupts cardioprotective signaling. The authors investigated whether mitochondrial DNA (mtDNA) modulates anesthetic preconditioning (APC) and cardiac susceptibility to ischemia-reperfusion injury by using two strains of rats, both sharing nuclear genome of type 2 diabetes mellitus (T2DN) rats and having distinct mitochondrial genomes of Wistar and fawn-hooded hypertensive (FHH) rat strains (T2DN(mtWistar) and T2DN(mtFHH), respectively).

Methods: Myocardial infarct size was measured in Wistar, T2DN(mtWistar), and T2DN(mtFHH) rats with or without APC (1.

Preconditioning by isoflurane elicits mitochondrial protective mechanisms independent of sarcolemmal KATP channel in mouse cardiomyocytes.

Cardiac mitochondria and the sarcolemmal (sarc)KATP channels contribute to cardioprotective signaling of anesthetic-induced preconditioning. Changes in mitochondrial bioenergetics influence the sarcolemmal ATP-sensitive K (sarcKATP) channel function, but whether this channel has impacts on mitochondria is uncertain. We used the mouse model with deleted pore-forming Kir6.

Comparison of cardiomyogenic potential among human ESC and iPSC lines.

We recently reported that, following induction of clumps of pluripotent H1 human embryonic stem cells (hESCs) with activin-A and Bmp4 in defined medium for 5 days, widespread differentiation of rhythmically contracting cardiomyocytes occurs within 3-4 weeks. In this study, the same approach was used to assess whether human induced pluripotent stem cells (hiPSCs), which may theoretically provide an unlimited source of patient-matched cells for transplantation therapy, can similarly undergo cardiomyocyte differentiation. Differentiation of four pluripotent cell lines (H1 and H9 hESCs and C2a and C6a hiPSCs) was compared in parallel by monitoring rhythmic contraction, morphologic differentiation, and expression of cardiomyogenic genes.

Marked hyperglycemia attenuates anesthetic preconditioning in human-induced pluripotent stem cell-derived cardiomyocytes.

Introduction: Anesthetic preconditioning protects cardiomyocytes from oxidative stress-induced injury, but it is ineffective in patients with diabetes mellitus. To address the role of hyperglycemia in the inability of diabetic individuals to be preconditioned, we used human cardiomyocytes differentiated from induced pluripotent stem cells generated from patients with or without type 2 diabetes mellitus (DM-iPSC- and N-iPSC-CMs, respectively) to investigate the efficacy of preconditioning in varying glucose conditions (5, 11, and 25 mM).

Methods: Induced pluripotent stem cells were induced to generate cardiomyocytes by directed differentiation.

Complex I and ATP synthase mediate membrane depolarization and matrix acidification by isoflurane in mitochondria.

Short application of the volatile anesthetic isoflurane at reperfusion after ischemia exerts strong protection of the heart against injury. Mild depolarization and acidification of the mitochondrial matrix are involved in the protective mechanisms of isoflurane, but the molecular basis for these changes is not clear. In this study, mitochondrial respiration, membrane potential, matrix pH, matrix swelling, ATP synthesis and -hydrolysis, and H(2)O(2) release were assessed in isolated mitochondria.

Biphasic effect of nitric oxide on the cardiac voltage-dependent anion channel.

Nitric oxide (NO·) effects on the cardiac mitochondrial voltage-dependent anion channel (VDAC) are unknown. The effects of exogenous NO· on VDAC purified from rat hearts were investigated in this study. When incorporated into lipid bilayers, VDAC was inhibited directly by an NO· donor, PAPA NONOate, in a concentration-dependent biphasic manner.

Isoflurane preconditioning elicits competent endogenous mechanisms of protection from oxidative stress in cardiomyocytes derived from human embryonic stem cells.

Background: Human embryonic stem cell (hESC)-derived cardiomyocytes potentially represent a powerful experimental model complementary to myocardium obtained from patients that is relatively inaccessible for research purposes. We tested whether anesthetic-induced preconditioning (APC) with isoflurane elicits competent protective mechanisms in hESC-derived cardiomyocytes against oxidative stress to be used as a model of human cardiomyocytes for studying preconditioning.

Methods: H1 hESC cell line was differentiated into cardiomyocytes using growth factors activin A and bone morphogenetic protein-4.

Generation of human induced pluripotent stem cells by simple transient transfection of plasmid DNA encoding reprogramming factors.

Background: The use of lentiviruses to reprogram human somatic cells into induced pluripotent stem (iPS) cells could limit their therapeutic usefulness due to the integration of viral DNA sequences into the genome of the recipient cell. Recent work has demonstrated that human iPS cells can be generated using episomal plasmids, excisable transposons, adeno or sendai viruses, mRNA, or recombinant proteins. While these approaches offer an advance, the protocols have some drawbacks.

Monitoring mitochondrial electron fluxes using NAD(P)H-flavoprotein fluorometry reveals complex action of isoflurane on cardiomyocytes.

Mitochondrial bioenergetic studies mostly rely on isolated mitochondria thus excluding the regulatory role of other cellular compartments important for the overall mitochondrial function. In intact cardiomyocytes, we followed the dynamics of electron fluxes along specific sites of the electron transport chain (ETC) by simultaneous detection of NAD(P)H and flavoprotein (FP) fluorescence intensities using a laser-scanning confocal microscope. This method was used to delineate the effects of isoflurane, a volatile anesthetic and cardioprotective agent, on the ETC.