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1.
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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2.
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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3.
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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4.
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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5.
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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6.
Association Between the Level of Reported Good Medication Adherence and the Geographic Location of a Patient's Residence and Presence of a Glucometer Among Adult Patients with Diabetes in Ethiopia: A Systematic and Meta-Analysis.
Dessie, G, Wagnew, F, Mulugeta, H, Belachew, A, Negesse, A, Kassa, GM, Habtewold, TD, Parchinski, K
Current therapeutic research, clinical and experimental. 2020;:100585
Abstract
BACKGROUND Diabetes mellitus (DM) is a major public health problem worldwide that was estimated to have affected the lives of 425 million people globally in 2017. The prevalence and mortality rates of DM have increased rapidly in low- and middle-income countries with an estimated 2.6 million cases of DM occurring in Ethiopia alone in 2015. OBJECTIVE Considering that Ethiopia is undergoing an epidemiological transition, it is increasingly important to understand the significant influence DM has on Ethiopians annually. A systematic review and meta-analysis of the existing studies were conducted to better understand the factors that are associated with DM medication adherence across Ethiopia and to elucidate areas for further studies. METHODS Studies were retrieved through search engines in Cumulative Index to Nursing and Allied Health Literature, Embase, Medline, PubMed, Google Scholar, Web of Science, Science Direct, and Scopus. The Newcastle-Ottawa Scale for cross-sectional studies was used to assess the critical appraisal of the included studies. Random effects model was used to estimate the association between the level of medication adherence and the geographic location of a patient's residence and presence of a glucometer at 95% CI with its respective odds ratio. Meta-regression was also used to identify the potential source of heterogeneity. Beggs and Egger tests were performed to determine publication bias. Subgroup analyses, based on the study area, were also performed. RESULTS A total of 1046 articles were identified through searching, of which 19 articles representing 7756 participants were included for the final analysis stage. Reported good medication adherence among patients with diabetes in Ethiopia was 68.59% (95% CI, 62.00%-75.18%). Subgroup analysis was performed, and the pooled estimate of reported good medication adherence among these patients in regions outside Addis Ababa was 67.81% (95% CI, 59.96%-75.65%), whereas in Addis Ababa it was 70.37% (95% CI, 57.51%-83.23%). Patients who used a glucometer at home had an odds ratio of 2.12 (95% CI, 1.42-3.16) and thus reported good adherence. We found no statistically significant association between the geographic location of a patient's residence and a good level of reported medication adherence (odds ratio, 1.81; 95% CI, 0.78-4.21). CONCLUSIONS Most adult patients with diabetes in these studies had a good level of reported DM medication adherence. Having a glucometer was significantly associated with reported increased medication adherence. Our findings suggest the need for interventions to improve diabetes medication adherence.
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7.
Hypertriglyceridemia-Causes, Significance, and Approaches to Therapy.
Santos-Baez, LS, Ginsberg, HN
Frontiers in endocrinology. 2020;:616
Abstract
Hypertriglyceridemia (HTG) is a common metabolic disorder with both genetic and lifestyle factors playing significant roles in its pathophysiology. HTG poses a risk for the development of cardiovascular disease (CVD) in the population at large and for pancreatitis in about two percent of individuals with extremely high levels of triglycerides (TG). This manuscript summarizes the mechanisms underlying the development of HTG as well as its management, including emerging therapies targeted at specific molecular pathways.
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8.
Polymerase iota - an odd sibling among Y family polymerases.
McIntyre, J
DNA repair. 2020;:102753
Abstract
It has been two decades since the discovery of the most mutagenic human DNA polymerase, polymerase iota (Polι). Since then, the biochemical activity of this translesion synthesis (TLS) enzyme has been extensively explored, mostly through in vitro experiments, with some insight into its cellular activity. Polι is one of four members of the Y-family of polymerases, which are the best characterized DNA damage-tolerant polymerases involved in TLS. Polι shares some common Y-family features, including low catalytic efficiency and processivity, high infidelity, the ability to bypass some DNA lesions, and a deficiency in 3'→5' exonucleolytic proofreading. However, Polι exhibits numerous properties unique among the Y-family enzymes. Polι has an unusual catalytic pocket structure and prefers Hoogsteen over Watson-Crick pairing, and its replication fidelity strongly depends on the template; further, it prefers Mn2+ ions rather than Mg2+ as catalytic activators. In addition to its polymerase activity, Polι possesses also 5'-deoxyribose phosphate (dRP) lyase activity, and its ability to participate in base excision repair has been shown. As a highly error-prone polymerase, its regulation is crucial and mostly involves posttranslational modifications and protein-protein interactions. The upregulation and downregulation of Polι are correlated with different types of cancer and suggestions regarding the possible function of this polymerase have emerged from studies of various cancer lines. Nonetheless, after twenty years of research, the biological function of Polι certainly remains unresolved.
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9.
Toward the 'golden' era: The status in uncovering the regulatory control of carotenoid accumulation in plants.
Sun, T, Li, L
Plant science : an international journal of experimental plant biology. 2020;:110331
Abstract
Carotenoids are essential pigments to plants and important natural products to humans. Carotenoids as both primary and specialized metabolites fulfill multifaceted functions in plants. As such, carotenoid accumulation (a net process of biosynthesis, degradation and sequestration) is subjected to complicated regulation throughout plant life cycle in response to developmental and environmental signals. Investigation of transcriptional regulation of carotenoid metabolic genes remains the focus in understanding the regulatory control of carotenoid accumulation. While discovery of bona fide carotenoid metabolic regulators is still challenging, the recent progress of identification of various transcription factors and regulators helps us to construct hierarchical regulatory network of carotenoid accumulation. The elucidation of carotenoid regulatory mechanisms at protein level and in chromoplast provides some insights into post-translational regulation of carotenogenic enzymes and carotenoid sequestration in plastid sink. This review briefly describes the pathways and main flux-controlling steps for carotenoid accumulation in plants. It highlights our recent understanding of the regulatory mechanisms underlying carotenoid accumulation at both transcriptional and post-translational levels. It also discusses the opportunities to expand toolbox for further shedding light upon the intrinsic regulation of carotenoid accumulation in plants.
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10.
Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in the Brain and Relevance for Neuropsychiatric Disorders.
O'Connell, EM, Lohoff, FW
Frontiers in neuroscience. 2020;:609
Abstract
Proprotein convertase subtilisin/kexin type 9 (PCSK9) has long been studied in the liver due to its regulation of plasma low-density lipoprotein cholesterol (LDL-C) and its causal role in familial hypercholesterolemia. Although PCSK9 was first discovered in cerebellar neurons undergoing apoptosis, its function in the central nervous system (CNS) is less clear. PCSK9 has been shown to be involved in neuronal differentiation, LDL receptor family metabolism, apoptosis, and inflammation in the brain, but in vitro and in vivo studies offer contradictory findings. PCSK9 expression in the adult brain is low but is highly upregulated during disease states. Cerebral spinal fluid (CSF) PCSK9 concentrations are correlated with neural tube defects and neurodegenerative diseases in human patients. Epigenetic studies reveal that chronic alcohol use may modulate methylation of the PCSK9 gene and genetic studies show that patients with gain-of-function PCSK9 variants have higher LDL-C and an increased risk of ischemic stroke. Early safety studies of the PCSK9 inhibitors evolocumab and alirocumab, used to treat hypercholesterolemia, hinted that PCSK9 inhibition may negatively impact cognition but more recent, longer-term clinical trials found no adverse neurocognitive events. The purpose of this review is to elucidate the role of PCSK9 in the brain, particularly its role in disease pathogenesis.