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1.
[Prognosis of bleeding recurrence after endoscopic sclerotherapy of esophageal varices].
Mogilevets, EV, Vorobey, AV, Garelik, PV
Khirurgiia. 2020;(10):60-67
Abstract
OBJECTIVE To improve prediction of recurrent bleeding after endoscopic sclerotherapy of esophageal varices. MATERIAL AND METHODS A prospective, observational, case-control study was performed. Immediate and long-term results of endoscopic sclerotherapy of esophageal varices were studied in 91 patients for the period from 2002 to 2016. Multiple regression analysis with binary response model was applied to analyze the prediction models. RESULTS Recurrent bleeding occurred in 80.5 (20; 182) days after sclerotherapy (range 0-2557 days). Spearman's correlation analysis revealed a significant relationship between bleeding recurrence and erythrocyte count (R= -0.32), Child-Pugh class of liver cirrhosis (R=0.49), Child-Pugh score (5-15) (R=0.54), content of amino acids, HPro/Pro ratio (R=0.71). Prognostic indicators were selected by stepwise inclusion of predictors. Thus, the final version of regression equation is as follows: Y=exp (-0.17+0.93×Child-Pugh score-106.42×HPro/Pro)/[1+exp(-0.17+0.93×Child-Pugh score-106.42×HPro/Pro)]. High risk of recurrent bleeding from esophageal varices within 1 year after endoscopic sclerotherapy is determined by Y-value >0.5. An accuracy of this model is 89.6%, Se 94.3%, Sp 79.2%, PPV 90.9%, NPV 86.4%, OR 63.3, LR + 4.53, LR - 0.07. CONCLUSION Thus, the proposed method is highly informative, effective, available and can be widely used in clinical practice.
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2.
Water Distribution and Clustering on the Lyophilized IgG1 Surface: Insight from Molecular Dynamics Simulations.
Feng, S, Peters, GHJ, Ohtake, S, Schöneich, C, Shalaev, E
Molecular pharmaceutics. 2020;(3):900-908
Abstract
Water has a critical role in the stability of the higher-order structure of proteins. In addition, it is considered to be a major destabilization factor for the physical and chemical stability of freeze-dried proteins and peptides. Physical and chemical aspects of protein/water relationships are commonly studied with the use of water vapor sorption isotherms for amorphous lyophilized proteins, which, in turn, are commonly analyzed using the Brunauer-Emmett-Teller (BET) equation to obtain the parameters, Wm and CB. The parameter Wm is generally referred to as the "monolayer limit of adsorption" and has a narrow range of 6-8% for most proteins. In this study, the water distribution on an IgG1 surface is investigated by molecular dynamics (MD) simulations at different water contents. The monolayer of water molecules was found to have limited coverage of the protein surface, and the true monolayer coverage of the protein globule actually occurs at a hydration level above 30%. The distribution of water molecules on the IgG1 surface is also highly heterogeneous, and the heterogeneity is not considered in the BET theory. In this study, a mechanistic model has been developed to describe the water vapor sorption isotherm. This model is based on the analysis of the hydrogen bonding network extracted from the MD simulations. The model is consistent with the experimental Type-II isotherm, which is usually observed for proteins. The physical meaning of the BET monolayer was redefined as the onset of water cluster formation. A simple model to calculate the onset water level, Wm, is proposed based on the hydration of different amino acids, as determined from the MD simulations.
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3.
Inferring Biochemical Reactions and Metabolite Structures to Understand Metabolic Pathway Drift.
Belcour, A, Girard, J, Aite, M, Delage, L, Trottier, C, Marteau, C, Leroux, C, Dittami, SM, Sauleau, P, Corre, E, et al
iScience. 2020;(2):100849
Abstract
Inferring genome-scale metabolic networks in emerging model organisms is challenged by incomplete biochemical knowledge and partial conservation of biochemical pathways during evolution. Therefore, specific bioinformatic tools are necessary to infer biochemical reactions and metabolic structures that can be checked experimentally. Using an integrative approach combining genomic and metabolomic data in the red algal model Chondrus crispus, we show that, even metabolic pathways considered as conserved, like sterols or mycosporine-like amino acid synthesis pathways, undergo substantial turnover. This phenomenon, here formally defined as "metabolic pathway drift," is consistent with findings from other areas of evolutionary biology, indicating that a given phenotype can be conserved even if the underlying molecular mechanisms are changing. We present a proof of concept with a methodological approach to formalize the logical reasoning necessary to infer reactions and molecular structures, abstracting molecular transformations based on previous biochemical knowledge.
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4.
Bioactivity, phytochemical profile and pro-healthy properties of Actinidia arguta: A review.
Pinto, D, Delerue-Matos, C, Rodrigues, F
Food research international (Ottawa, Ont.). 2020;:109449
Abstract
Hardy kiwi (Actinidia arguta) is a climbing, perennial and dioecious vine from Actinidiaceae family, native from Asia and valued as ornamental and traditional medicine. In the last decade, the growing interest as fruit-bearing plant encourage the expanding cultivation of A. arguta mainly to fruits production, particularly in Europe and North America. A. arguta plants have an extensive range ofbioactive compoundsthat can be obtained from different botanical structures, such as fruits, leaves, flowers and stems. These bioactive molecules, with well-recognized health-promoting properties, include phenolic compounds, minerals, carbohydrates or even volatile substances, with a great potential to be used in several formulations of food products. Phytochemical studies on this plant reported hypoglycemic effects as well as antioxidant and anti-inflammatory activities, among others. The traditional uses ofA. arguta have been experimentally proved byin vitroandin vivostudies, in which its bioactivities were associated to its phytochemical composition. This review aims to assess and summarize the phytochemical and healthy properties ofthe different botanical parts of A. arguta, describing their bioactive composition and exploring it potential functional properties on foodstuffs.
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5.
AIF meets the CHCHD4/Mia40-dependent mitochondrial import pathway.
Reinhardt, C, Arena, G, Nedara, K, Edwards, R, Brenner, C, Tokatlidis, K, Modjtahedi, N
Biochimica et biophysica acta. Molecular basis of disease. 2020;(6):165746
Abstract
In the mitochondria of healthy cells, Apoptosis-Inducing factor (AIF) is required for the optimal functioning of the respiratory chain machinery, mitochondrial integrity, cell survival, and proliferation. In all analysed species, it was revealed that the downregulation or depletion of AIF provokes mainly the post-transcriptional loss of respiratory chain Complex I protein subunits. Recent progress in the field has revealed that AIF fulfils its mitochondrial pro-survival function by interacting physically and functionally with CHCHD4, the evolutionarily-conserved human homolog of yeast Mia40. The redox-regulated CHCHD4/Mia40-dependent import machinery operates in the intermembrane space of the mitochondrion and controls the import of a set of nuclear-encoded cysteine-motif carrying protein substrates. In addition to their participation in the biogenesis of specific respiratory chain protein subunits, CHCHD4/Mia40 substrates are also implicated in the control of redox regulation, antioxidant response, translation, lipid homeostasis and mitochondrial ultrastructure and dynamics. Here, we discuss recent insights on the AIF/CHCHD4-dependent protein import pathway and review current data concerning the CHCHD4/Mia40 protein substrates in metazoan. Recent findings and the identification of disease-associated mutations in AIF or in specific CHCHD4/Mia40 substrates have highlighted these proteins as potential therapeutic targets in a variety of human disorders.
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6.
Anticonvulsant mechanisms of the ketogenic diet and caloric restriction.
Rudy, L, Carmen, R, Daniel, R, Artemio, R, Moisés, RO
Epilepsy research. 2020;:106499
Abstract
Many treatments have been proposed to control epileptic seizures, such as the ketogenic diet and caloric restriction. However, seizure control has not yet been improved completely in all patients. Probably, due to the lack of understanding regarding this neurological disorder pathogenesis or pathophysiology, including its molecular approach. Currently, there is not much information about the molecular processes and genes involved, and their relation to the possible beneficial effects of diet therapy on epilepsy. The ketogenic diet and caloric restriction are implicated in potential anti-seizure mechanisms related to the gut microbiome, metabolic pathways, hormones and neurotransmitters, mitochondria improvement, a role in inflammation, and oxidative stress, among others. In this review, we pretend to describe the molecular mechanism and the possible genes involved in the different ketogenic diet and caloric restriction mechanisms of action described to decrease neural excitability and, therefore, epileptic seizures, especially when conventional treatment is not enough to achieve control of epilepsy.
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7.
A comparison between drug-eluting stent implantation and drug-coated balloon angioplasty in patients with left main bifurcation in-stent restenotic lesions.
Kook, H, Joo, HJ, Park, JH, Hong, SJ, Yu, CW, Lim, DS
BMC cardiovascular disorders. 2020;(1):83
Abstract
BACKGROUND The current guidelines recommend both repeat stenting and drug-coated balloons (DCB) for in-stent restenosis (ISR) lesions, if technically feasible. However, real-world clinical data on the interventional strategies in patients with left main bifurcation (LMB)-ISR have not been elucidated. METHODS Seventy-five patients with LMB-ISR, who underwent percutaneous coronary intervention (PCI) between January 2009 and July 2015, were retrospectively reviewed for the present study (repeat drug eluting stent [DES] implantation [n = 51], DCB angioplasty [n = 24]). RESULTS Analysis of the baseline characteristics showed that the patients in the DCB group had a lower incidence of non-ST segment elevation myocardial infarction/ST segment elevation myocardial infarction at the index PCI (8.3% vs. 25.5%; p = 0.12), higher low-density lipoprotein-cholesterol level (92.9 mg/dL vs. 81.7 mg/dL; p = 0.09), and more "stent-in-stent" lesions (25% vs. 7.8%; p = 0.07) than those in the DES group. A smaller post-procedural minimal target lesion lumen diameter was also noted in the DCB group than in the DES group (2.71 mm vs. 2.85 mm; p = 0.03). The cumulative incidence rates of major adverse cardiac events (MACEs) were similar between both groups (median follow-up duration, 868 days; MACE rate, 25% in the DCB group vs. 25.5% in the DES group; p = 0.96). The multivariate Cox regression analysis indicated that the true bifurcation of ISR was an independent risk predictor of MACEs (hazard ratio, 4.62; 95% confidence interval, 1.572-13.561; p < 0.01). CONCLUSIONS DES and DCB showed comparable long-term clinical results in patients with LMB-ISR lesions.
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8.
CITROBACTER ENDOGENOUS ENDOPHTHALMITIS: A CASE REPORT AND REVIEW OF THE LITERATURE.
Wong, DHT, Liu, CCH, Tong, JMK, Luk, WK, Li, KKW
Retinal cases & brief reports. 2020;(2):187-191
Abstract
PURPOSE We present a case of endogenous endophthalmitis because of an unusual bacterium, Citrobacter koseri. PATIENT A 57-year-old woman without previous history of eye surgery or trauma presented with diabetic ketoacidosis and a painful right eye with the reduction of vision. C. koseri was identified in blood culture; thus, a diagnosis of right eye endogenous endophthalmitis was made. Intravenous and intravitreal antibiotics were both started, and vitreous culture further confirmed C. koseri as the causative organism. Computed tomography of the abdomen and pelvis revealed a right C-shaped perinephric abscess, which was drained under ultrasound guidance. RESULTS Because of rapid progression to corneal melting, evisceration was performed. CONCLUSION Cases of endogenous endophthalmitis caused by Citrobacter are very limited, and a review of all published cases in the English literature and the present case revealed that endogenous Citrobacter endophthalmitis arose almost entirely from Citrobacter renal infection. Early recognition and drainage of renal abscess may lower the chance of uncontrolled infection and endogenous spread to the eyes. Despite prompt and intensive treatment, the clinical outcome of Citrobacter endogenous endophthalmitis seems to be poor.
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9.
Prohibitin ligands: a growing armamentarium to tackle cancers, osteoporosis, inflammatory, cardiac and neurological diseases.
Wang, D, Tabti, R, Elderwish, S, Abou-Hamdan, H, Djehal, A, Yu, P, Yurugi, H, Rajalingam, K, Nebigil, CG, Désaubry, L
Cellular and molecular life sciences : CMLS. 2020;(18):3525-3546
Abstract
Over the last three decades, the scaffold proteins prohibitins-1 and -2 (PHB1/2) have emerged as key signaling proteins regulating a myriad of signaling pathways in health and diseases. Small molecules targeting PHBs display promising effects against cancers, osteoporosis, inflammatory, cardiac and neurodegenerative diseases. This review provides an updated overview of the various classes of PHB ligands, with an emphasis on their mechanism of action and therapeutic potential. We also describe how these ligands have been used to explore PHB signaling in different physiological and pathological settings.
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10.
Generation of three induced pluripotent stem cell lines (MHHi012-A, MHHi013-A, MHHi014-A) from a family with Loeys-Dietz syndrome carrying a heterozygous p.M253I (c.759G>A) mutation in the TGFBR1 gene.
Pongpamorn, P, Dahlmann, J, Haase, A, Ebeling, CT, Merkert, S, Göhring, G, Lachmann, N, Martens, A, Haverich, A, Martin, U, et al
Stem cell research. 2020;:101707
Abstract
Loeys-Dietz syndrome (LDS) is a rare connective tissue disorder characterized by a genetic predisposition for thoracic aortic aneurysm and dissection. Despite heterozygous loss-of-function mutations in genes for ligand, receptor, or downstream mediators of the transforming growth factor β (TGFβ) pathway, LDS is associated with a signature of high TGFβ signaling. We generated induced pluripotent stem cell (iPSC) lines from three adult LDS-patients (two male, one female) of a family with a heterozygous point mutation in exon 4 of the TGFβ-receptor1 (TGFBR1) gene (p.M253I; c.759G>A). The lines offer a valuable resource for modeling the pathophysiology of genetically mediated aortic disease.