Physiopathological Changes Research Articles

Nicotinamide Mononucleotide in the Context of Myocardiocyte Longevity.

Cellular and subcellular metabolic activities are crucial processes involved in the regulation of intracellular homeostasis, including cellular and subcellular signaling pathways. Dysregulation of intracellular regulation mechanisms is catastrophic and cumulates into cell death. To overcome the issue of dysregulation of intracellular regulation mechanisms, the preservation of subcellular and extracellular components is essential to maintain healthy cells with increased longevity. Several physiopathological changes occur during cell ageing, one of which is the dysregulation of intracellular physiology of the oxidative phosphorylation process. Nicotinamide mononucleotide (NMN) remains in the debut of anti-aging therapeutic effect. Aged myocardiocyte characterized by disrupted NMN and or its precursors or signaling pathways. Simultaneously, several other pathophysiological occur that collectively impair intracellular homeostasis. The NMN role in the antiaging effect remains unclear and several hypotheses have been introduced into describing the mechanism and the potential outcomes from NMN exogenous supply. Correction of the impaired intracellular homeostasis includes correction to the NMN metabolism. Additionally, autophagy correction, which is the key element in the regulation of intracellular intoxication, including oxidative stress, unfolding protein response, and other degradation of intracellular metabolites. Several signaling pathways are involved in the regulation mechanism of NMN effects on myocardiocyte health and further longevity. NMN protects myocardiocytes from ischemic injury by reducing anabolism and, increasing catabolism and further passing the myocardiocytes into dormant status. NMN applications include ischemic heart, disease, and failed heart, as well as dilated cardiomyopathies. Cytosolic and mitochondrial NADPH are independently functioning and regulating. Each of these plays a role in the determination of the longevity of the myocardiocytes. NMN has a cornerstone in the functionality of Sirtuins, which are an essential anti-senescent intrinsic molecule. The study aims to assess the role of NMN in the longevity and antisenescent of myocardiocytes.

Nutritional Fuelling for Microgravity Environment of Space Missions

Abstract: Since the beginning of space missions, the food systems have undergone a sea change with prolonged manned missions and permanent space habitats. We have a better understanding of physiological changes which happen in humans in space and help in adaptation to the space environment. Yet, much remains underexplored and warrants further research. Space missions today involve a considerable number of individuals operating in a microgravity environment for both short and long periods. The provision of food for such missions and managing the physio-pathological changes that affect nutritional requirements continue to be challenging. Food systems (food and beverages) used during every program to date have been shelf‐stable and were composed primarily of rehydratable or thermostabilized food items. Such foods usually have a lower hedonic value than fresh or frozen foods. Consequently, a reliable food system must provide a wide range of palatable and attractive foods as well as the tools to prepare them (through rehydration, heating, and cooling) to enhance the taste sensation of the crew. Adequate nutrition with easily accessible food is essential to this effort. To deliver nutritional recommendations to crew members for long-duration space missions, it is important to understand how nutritional status and general physiology are linked and affected by microgravity exposure. In view of this, it has been pointed out that nutritional countermeasures could rectify the physiological and behavioural anomalies during microgravity exposure. In this comprehensive narrative review, we have provided an overview of a few recent advances such as silkworm protein, good mood-vegan diet, 3-D food printing, and space garden’s produce for onboard support to food systems. It has also been found that exercise could be an addition to nutritional interventions. Areas of space exploration that require more in-depth research using ground-based bed rest models, as well as inflight microgravity conditions, are highlighted.

A New Strategy for the Regulation of Neuroinflammation: Exosomes Derived from Mesenchymal Stem Cells.

Neuroinflammation is an important pathogenesis of neurological diseases and causes a series of physiopathological changes, such as abnormal activation of glial cells, neuronal degeneration and death, and disruption of the blood‒brain barrier. Therefore, modulating inflammation may be an important therapeutic tool for treating neurological diseases. Mesenchymal stem cells (MSCs), as pluripotent stem cells, have great therapeutic potential for neurological diseases due to their regenerative ability, immunity, and ability to regulate inflammation. However, recent studies have shown that MSC-derived exosomes (MSC-Exos) play a major role in this process and play a key role in neuroprotection by regulating neuroglia. This review summarizes the recent progress made in regulating neuroinflammation by focusing on the mechanisms by which MSC-Exos are involved in the regulation of glial cells through signaling pathways such as the TLR, NF-κB, MAPK, STAT, and NLRP3 pathways to provide some references for subsequent research and therapy.

Hormones and thrombosis: the dark side of the moon.

The main drawback of oral contraceptives (OC) and hormone replacement therapy (HRT) is an increased risk of venous and, to a lesser extent, arterial thrombosis. This narrative, case-based review describes the effect of available estrogens and progestogens on the hemostatic system and their potential impact on the risk of thrombosis. Clinical cases are used to illustrate different options for prescribing OC and HRT in the real-word. The aim is to offer discussion topics that could be helpful to guide the choice of different hormonal treatments over a woman's lifetime and in the presence of risk factors. We describe physio-pathological changes occurring during the administration of hormonal therapies. Furthermore, we analyze the risk of venous and arterial thrombosis associated with different products, routes of administration and additional risk factors. New hormonal preparations, such as estradiol combined with dienogest, as well as non-oral hormonal therapies, are suggested to decrease thrombotic risk significantly. The availability of many products and different routes of administration allow most women to safely use contraception, as well as HRT. We encourage careful counselling instead of inflexible or fearful behavior, as expanding options and choices will allow women to make the best decisions for their health.

Changes of the salivary and serum proteome in canine hypothyroidism

In this study, changes in salivary and serum proteome of dogs with hypothyroidism were studied using tandem mass tags (TMT) labelling and liquid chromatography-mass spectrometry (LC-MS/MS). Saliva and serum proteome from 10 dogs with hypothyroidism were compared with 10 healthy dogs. In saliva, a total of seven proteins showed significant changes between the two groups, being six downregulated and one upregulated, meanwhile, in serum, a total of six proteins showed significant changes, being five downregulated and one upregulated. The altered proteins reflected metabolic and immunologic changes, as well as, skin and coagulation alterations, and these proteins were not affected by gender. One of the proteins that were downregulated in saliva, lactate dehydrognease (LDH), was measured by a spectrophotometric assay in saliva samples from 42 dogs with hypothyroidism, 42 dogs with non-thyroid diseases and 46 healthy dogs. The activity of LDH was lower in the saliva of hypothyroid dogs when compared to non-thyroid diseased dogs and healthy controls.This study indicates that canine hypothyroidism can produce changes in the proteome of saliva and serum. These two sample types showed different variations in their proteins reflecting physiopathological changes that occur in this disease, mainly related to the immune system, metabolism, skin and coagulation. In addition, some of the proteins identified in this study, specially LDH in saliva, should be further explored as potential biomarkers of canine hypothyroidism.

Melatonin ameliorates serobiochemical alterations and restores the cardio-nephro diabetic vascular and cellular alterations in streptozotocin-induced diabetic rats.

Melatonin possesses a wide range of pharmacological activities, including antidiabetic properties. Diabetes mellitus (DM) induces several physiopathological changes in body organs, which could be observed lately after systemic failure. In the current study, we aimed to investigate the serobiochemical changes and the histopathological picture in the diabetic heart and the kidney early before chronic complications and highlight the association between hyperglycemia, glomerular alterations, and cardiovascular changes. In addition, the role of melatonin in the treatment of cardio-nephro diabetic vascular and cellular adverse changes in streptozotocin-induced diabetic rats was also studied. A total of 40 mature Wistar albino rats were distributed into five groups; (1) control untreated rats, (2) diabetic mellitus untreated (DM) rats, in which DM was induced by the injection of streptozotocin (STZ), (3) control melatonin-treated (MLT), (4) melatonin-treated diabetic (DM + MLT) rats, in which melatonin was injected (10 mg/kg/day, i.p.) for 4 weeks, and (5) insulin-treated diabetic (DM + INS) rats. The serum biochemical analysis of diabetic STZ rats showed a significant (P < 0.05) increase in the concentrations of blood glucose, total oxidative capacity (TOC), CK-MB, endothelin-1, myoglobin, H-FABP, ALT, AST, urea, and creatinine as compared to control rats. In contrast, there was a significant (P < 0.05) decrease in serum concentration of insulin, total antioxidative capacity (TAC), total nitric oxide (TNO), and total protein level in DM rats vs. the control rats. Significant improvement in the serobiochemical parameters was noticed in both (DM + MLT) and (DM + INS) groups as compared with (DM) rats. The histological examination of the DM group revealed a disorder of myofibers, cardiomyocyte nuclei, and an increase in connective tissue deposits in between cardiac tissues. Severe congestion and dilation of blood capillaries between cardiac muscle fibers were also observed. The nephropathic changes in DM rats revealed various deteriorations in glomeruli and renal tubular cells of the same group. In addition, vascular alterations in the arcuate artery at the corticomedullary junction and interstitial congestion take place. Melatonin administration repaired all these histopathological alterations to near-control levels. The study concluded that melatonin could be an effective therapeutic molecule for restoring serobiochemical and tissue histopathological alterations during diabetes mellitus.

Changes in cerebral oxygen saturation with the Trendelenburg position and increased intraabdominal pressure in laparocopic rectal surgery.

Position changes and increased intra-abdominal pressure in laparoscopic interventions lead to some physiopathological changes. There is no definite information in the literature regarding cerebral oxygen saturation in patients undergoing colorectal surgery. Our aim was to investigate whether there is oxygen saturation change in the brain tissue in pneumoperitoneum and the Trendelenburg position during laparoscopic rectal surgery. Cerebral oxygen saturation was measured in 35 patients who underwent laparoscopic rectal surgery in the Trendelenburg position. Measurements were made under general anesthesia in the pneumoperitoneum and the Trendelenburg position. The values that are statistically affected by the position are systolic blood pressure, mean arterial blood pressure and cerebral oxygen saturation. The Trendelenburg position does not disturb the cerebral oxygen saturation and it causes an increase in saturation. After pneumoperitoneum occurred, changes in systolic blood pressure, mean arterial blood pressure and brain oxygen saturation were detected. Cerebral oxygen saturation increases with the formation of pneumoperitoneum. The Trendelenburg position and increased intraabdominal pressure during laparoscopic rectal surgery do not impair brain oxygen saturation.

Characterization of early myocardial inflammation in ischemia-reperfusion injury.

Myocardial injury may be caused by myocardial ischemia-reperfusion (IR), and salvaging such an injury is still a great challenge in clinical practice. This study comprehensively characterized the physiopathologic changes of myocardial injury after IR to explore the underlying mechanism in the early reperfusion phase with particular emphasis on early myocardial inflammation. The experimental IR model was obtained by the left anterior descending artery's transient ligation of C57BL/6 mice. T2W signals of all mice showed increased signal at different IR stages. It was positively correlated with inflammatory cytokines and cells. T2W imaging by 7.0 T MRI surprisingly detected signal enhancement, but histopathology and flow cytometry did not reveal any inflammatory cells infiltration within 3 h after IR. Cardiomyocyte swelling and increased vascular permeability were observed by WGA staining and ultrastructural analysis, respectively. The 3 h IR group showed that the cardiomyocytes were severely affected with disintegrating myofilaments and mitochondria. Both VEGF and phosphorylated Src protein were markedly expressed in the 3 h IR group in comparison with the sham group, and TUNEL staining displayed little positive cells. Cleaved caspase-3 apoptin also has similar expression levels with that of the sham group. Resident macrophages had notably become M1 phenotype. The T2W signal was still elevated, and we observed that collagen deposition occurred from 1 to 7 days. The inflammation response during the first week after reperfusion injury gradually increase 3 h later, but the main manifestation before that was edema. This study indicated that the first 3 h may be crucial to the early rescue process for reperfusion-induced myocardial injury due to inflammatory cell infiltration absence and apoptosis.

Physiopathological changes of ferritin mRNA density and distribution in hippocampal astrocytes in the mouse brain.

Astrocytes are thought to play a crucial role in brain iron homeostasis. How they accomplish this regulation in vivo is unclear. In a recent transcriptomic analysis, we showed that polysomal Ftl1 and Fth1 mRNAs, encoding the ferritin light (Ftl) and heavy (Fth) chains that assemble into ferritin, a critical complex for iron storage and reduction, are enriched in perisynaptic astrocytic processes as compared to astrocytic soma. These data suggested that ferritin translation plays a specific role at the perisynaptic astrocytic interface and is tighly regulated by local translation. Here, we used our recently described AstroDot 3D in situ methodology to study the density and localization of ferritin mRNAs in astrocytes in the hippocampus in three different contexts in which local or systemic iron overload has been documented: aging, the hepcidin knock-out mouse model of hemochromatosis and the APP/PS1dE9 mouse model of Alzheimer's disease (AD). Our results showed that in wild type mice, Fth1 mRNA density was higher than Ftl1 and that both mRNAs were mostly distributed in astrocyte fine processes. Aging and absence of hepcidin caused an increased Fth1/Ftl1 ratio in astrocytes and in the case of aging, led to a redistribution of Fth1 mRNAs in astrocytic fine processes. In contrast, in AD mice, we observed a lower Fth1/Ftl1 ratio. Fth1 mRNAs became more somatic and Ftl1 mRNAs redistributed in large processes of astrocytes proximal to Amyloid beta (Aß) deposits. Hence, we propose that regulation of ferritin mRNA density and distribution in astrocytes contribute to iron homeostasis in physiology and pathophysiology.

Molecular Hydrogen: an Emerging Therapeutic Medical Gas for Brain Disorders.

Oxidative stress and neuroinflammation are the main physiopathological changes involved in the initiation and progression of various neurodegenerative disorders or brain injuries. Since the landmark finding reported in 2007 found that hydrogen reduced the levels of peroxynitrite anions and hydroxyl free radicals in ischemic stroke, molecular hydrogen's antioxidative and anti-inflammatory effects have aroused widespread interest. Due to its excellent antioxidant and anti-inflammatory properties, hydrogen therapy via different routes of administration exhibits great therapeutic potential for a wide range of brain disorders, including Alzheimer's disease, neonatal hypoxic-ischemic encephalopathy, depression, anxiety, traumatic brain injury, ischemic stroke, Parkinson's disease, and multiple sclerosis. This paper reviews the routes for hydrogen administration, the effects of hydrogen on the previously mentioned brain disorders, and the primary mechanism underlying hydrogen's neuroprotection. Finally, we discuss hydrogen therapy's remaining issues and challenges in brain disorders. We conclude that understanding the exact molecular target, finding novel routes, and determining the optimal dosage for hydrogen administration is critical for future studies and applications.

Oxidative Stress and Intracranial Hypertension after Aneurysmal Subarachnoid Hemorrhage.

Intracranial hypertension is a common phenomenon in patients with aneurysmal subarachnoid hemorrhage (aSAH). Elevated intracranial pressure (ICP) plays an important role in early brain injuries and is associated with unfavorable outcomes. Despite advances in the management of aSAH, there is no consensus about the mechanisms involved in ICP increases after aSAH. Recently, a growing body of evidence suggests that oxidative stress (OS) may play a crucial role in physio-pathological changes following aSAH, which may also contribute to increased ICP. Herein, we discuss a potential relation between increased ICP and OS, and resultantly propose antioxidant mechanisms as a potential therapeutic strategy for the treatment of ICP elevation following aSAH.

Imaging Leucine-Rich Repeat Kinase 2 In Vivo with 18F-Labeled Positron Emission Tomography Ligand.

Leucine-rich repeat kinase 2 (LRRK2) has been demonstrated to be closely involved in the pathogenesis of Parkinson's disease (PD), and pharmacological blockade of LRRK2 represents a new opportunity for therapeutical treatment of PD and other related neurodegenerative conditions. The development of an LRRK2-specific positron emission tomography (PET) ligand would enable a target occupancy study in vivo and greatly facilitate LRRK2 drug discovery and clinical translation as well as provide a molecular imaging tool for studying physiopathological changes in neurodegenerative diseases. In this work, we present the design and development of compound 8 (PF-06455943) as a promising PET radioligand through a PET-specific structure-activity relationship optimization, followed by comprehensive pharmacology and ADME/neuroPK characterization. Following an efficient 18F-labeling method, we have confirmed high brain penetration of [18F]8 in nonhuman primates (NHPs) and validated its specific binding in vitro by autoradiography in postmortem NHP brain tissues and in vivo by PET imaging studies.

Coadministration of L-alanine and L-glutamine ameliorate blood glucose levels, biochemical indices and histological features in alloxan-induced diabetic rats.

We evaluated the effects of supplementation of L-alanine and L-glutamine on blood glucose levels and biochemical parameters in alloxan-induced diabetic rat. Forty-nine animals were distributed into seven equal groups. Except for the non-diabetic control, diabetes was induced in all groups by intravenous alloxan injection followed by daily supplementation with amino acids for 14 days. Weight and blood glucose were monitored during supplementation, while biochemical parameters such as liver and renal functions, lipid profile, and antioxidant markers were evaluated post-intervention. A significant increase (p < .05) in weight and decrease in blood glucose were observed in the amino acid(s) treated groups. The supplementation with both amino acids restored important tissue antioxidants, liver and kidney functions and rescued islets cells degeneration. Histopathological examinations of important tissues showed the restoration of alloxan-induced physiopathological changes by the amino acids. Thus, these amino acids might serve as nutraceuticals for the management and treatment of diabetes. PRACTICAL APPLICATIONS: The discovery and production of antidiabetic bioactive compounds are often challenging, and the existing antidiabetic drugs are expensive. Amino acids are key regulators of glucose metabolism, insulin secretion, and insulin sensitivity; thus, they can play a crucial role in alleviating diabetes. Here, we present findings that strongly suggest the potential of pure amino acids (L-alanine and L-glutamine) for the management and treatment of diabetes. We show that these amino acids, when supplemented singly or coadministered can lower blood glucose levels and restore several other biochemical parameters implicated in diabetes. Hence, these cheap amino acids may be consumed as nutraceuticals or food supplements by diabetics for the treatment/management of diabetes. Foods rich in these amino acids may also be consumed as part of the diet of diabetic patients.

A Human Stem Cell-Derived Neurosensory-Epithelial Circuitry on a Chip to Model Herpes Simplex Virus Reactivation.

Both emerging viruses and well-known viral pathogens endowed with neurotropism can either directly impair neuronal functions or induce physio-pathological changes by diffusing from the periphery through neurosensory–epithelial connections. However, developing a reliable and reproducible in vitro system modeling the connectivity between the different human sensory neurons and peripheral tissues is still a challenge and precludes the deepest comprehension of viral latency and reactivation at the cellular and molecular levels. This study shows a stable topographic neurosensory–epithelial connection on a chip using human stem cell-derived dorsal root ganglia (DRG) organoids. Bulk and single-cell transcriptomics showed that different combinations of key receptors for herpes simplex virus 1 (HSV-1) are expressed by each sensory neuronal cell type. This neuronal–epithelial circuitry enabled a detailed analysis of HSV infectivity, faithfully modeling its dynamics and cell type specificity. The reconstitution of an organized connectivity between human sensory neurons and keratinocytes into microfluidic chips provides a powerful in vitro platform for modeling viral latency and reactivation of human viral pathogens.

Factors Predicting Post-Traumatic Positive and Negative Psychological Changes Experienced by Nurses during a Pandemic COVID-19: A Cross-Sectional Study.

It is common knowledge that COVID-19 affects physiopathological changes in all systems of the human body. On the other hand, events related to the COVID-19 pandemic also have a significant impact on the social and mental sphere of human functioning. The aim of this study is to determine the relationship between selected sociodemographic variables and selected subjective cognitive resources, and the positive and negative perception of the consequences of the COVID-19 pandemic in a group of nurses working in Poland. The computer-assisted web interviewing method was conducted between 1 and 15 May 2020. Participants were requested to complete the following questionnaires: The Changes in Outlook Questionnaire (CIOQ), The Impact Event Scale-Revised (IES-R), The Multidimensional Scale of Perceived Social Support (MSPSS), The Safety Experience Questionnaire (SEQ), and The Meaning in Life Questionnaire (MLQ). Three-hundred and twenty fivenurses working all over Poland participated in the study. Their mean age was 39.18 ± 11.16 years. A higher average level was noted among the surveyed nurses in the Positive Change subscale (18.56 ± 4.04). In a multivariate model, taking into account both sociodemographic and cognitive variables, the level of perceived traumatic stress, the level of social support, a sense of security, reflection on safety and a sense of meaning and meaning in life were independent predictors of a positive perception of the consequences of the COVID-19 pandemic. Those variables explained as much as 37% of the dependent variable, and the nature of the relationship was positive. While we are still a long way from understanding the full range of the long-term impact of the COVID-19 pandemic on mental health and psychosocial well-being, it is possible that in this challenging context there are many individual resources available to perceive the effects of the current pandemic positively. Therefore, they should be strengthened through the development and implementation of intervention programs to improve the mental state of nurses.

The impact of maternal SARS-COV-2 infection in early stages of newborn neurodevelopment: preliminary results in a multicenter Spanish study

Introduction The consequences for the COVID-19 pandemic in the newborns of affected mothers remains unknown. Previous clinical experiences with other infections during pregnancy lead to considered pregnant women and their offspring especially vulnerable for SARS-COV-2. That is, the underlying physiopathological changes caused by the infection (e.g. storm of cytokines, micro-coagulation in placenta or vertical transmission) could clearly compromise fetal neurodevelopment.ObjectivesTo analyze the impact of maternal SARS-COV-2 infection during pregnancy in early neurodevelopment of infants gestated during the COVID-19 pandemic period compared to those gestated immediately prior (2017-2021).Methods 212 pregnant women (14% infected) were followed throughout their pregnancy and postpartum, including newborn development. SARS-COV-2 infection was serologically confirmed during pregnancy. The Brazelton Neonatal Assessment Scale (NBAS) was administered at 6 weeks old by a trained neonatologist to evaluate neurological, social and behavioral aspects of newborn’s functioning. Differences in NBAS scores between cases and controls were tested by ANOVAs. All the analysis were adjusted for maternal age, sociodemographic status, anxious-depressive symptomatology, infant’s sex and gestational age at birth and NBAS, and for the period of gestation (previous or during COVID-19 pandemic).ResultsNBAS social interactive dimension was significantly decreased in those infants exposed to prenatal SARS-COV-2 (F=4.248, p=.043), particularly when the infection occurred before the week 20 of gestation. Gestation during COVID-19 pandemic did not alter NBAS subscales.ConclusionsSARS-COV-2 infection during pregnancy seems to be associated with lower NBAS scores on social dimension in 6 weeks old exposed newborns.DisclosureNo significant relationships.

Tigecycline population pharmacokinetics in critically ill patients with decompensated cirrhosis and severe infections.

Physiopathological changes in advanced cirrhosis could alter tigecycline pharmacokinetics (PK), thus affecting serum drug concentrations and compromising target attainment. We aimed to describe tigecycline PK in patients with decompensated cirrhosis and severe bacterial infections, identify the sources of PK variability and assess the performance of different dosing regimens to optimize the PK/pharmacodynamic (PD) target. Serum concentrations and covariates were obtained from patients with severe infections under tigecycline treatment. A population PK analysis was performed using non-linear mixed-effects modelling and the final model was used to simulate tigecycline exposure to assess the PTA. Twenty critically ill patients were enrolled in the study. Data were best described by a two-compartment linear model. Mean ± SD parameter estimates for clearance (CL), intercompartmental clearance (Q), central and peripheral volumes of distribution (V1 and V2) were 14.8 ± 11 L/h, 38.4 ± 24 L/h, 63.7 ± 14 L and 233 ± 30 L, respectively. MELD score significantly influenced tigecycline CL, and total serum proteins significantly affected V1. Monte Carlo simulations showed that tigecycline elimination is hampered as MELD score values increase, consequently requiring lower drug doses. Patients with hypoproteinaemia would have lower peak tigecycline concentrations but similar steady-state concentrations compared with patients with normoproteinaemia. Our study confirms that tigecycline dose adjustment is needed in severe hepatic dysfunction and suggests using the MELD score for dose optimization since it is identified as a covariate that significantly influences tigecycline CL. Dosing regimens are recommended to reach several PK/PD targets considering this clinical variable and any MIC within the susceptibility range.

Retinal Degeneration: A Window to Understand the Origin and Progression of Parkinson’s Disease?

Parkinson’s disease (PD), the second most prevalent neurodegenerative disorder, manifests with motor and non-motor symptoms associated with two main pathological hallmarks, including the deterioration of dopaminergic cells and aggregation of alpha-synuclein. Yet, PD is a neurodegenerative process whose origin is uncertain and progression difficult to monitor and predict. Currently, a possibility is that PD may be secondary to long lasting peripheral affectations. In this regard, it has been shown that retinal degeneration is present in PD patients. Although it is unknown if retinal degeneration precedes PD motor symptoms, the possibility exists since degeneration of peripheral organs (e.g., olfaction, gut) have already been proven to antedate PD motor symptoms. In this paper, we explore this possibility by introducing the anatomical and functional relationship of retina and brain and providing an overview of the physiopathological changes of retinal structure and visual function in PD. On the basis of the current status of visual deficits in individuals with PD, we discuss the modalities and pathological mechanism of visual function or morphological changes in the retina and focus on the correlation between visual impairment and some representative structural features with clinical significance. To consider retinal degeneration as a contributor to PD origin and progress is important because PD evolution may be monitored and predicted by retinal studies through state-of-the-art techniques of the retina. It is significant to integrally understand the role of retinal morphological and functional changes in the neurodegenerative process for the diagnosis and therapeutic strategies of PD.

Non-Alkolik Yağlı Karaciğer Hastalığı Olan ve Olmayan Obez Çocuklarda Hepatik Vasküler Akım Değişikliklerinin Değerlendirilmesi

Objective: To evaluate hepatic vascular flow alterations using Doppler ultrasound in obese children with and without non-alcoholic fatty liver disease.Material and Methods: Ninety-one obese and 30 healthy lean (control) children were enrolled in this study. Obese children were divided into two groups: children with non-alcoholic fatty liver disease and children without non-alcoholic fatty liver disease; according to hepatic fatty changes on ultrasound, and blood serum alanine aminotransferase levels above 30 IU/L. Portal vein diameter, portal blood flow volume and hepatic artery resistive index were calculated using Doppler ultrasound.Results: Portal vein diameter and portal blood flow volume values in children with non-alcoholic fatty liver disease were found close to the controls. However, the values of portal vein diameter and portal blood flow volume were lower in children without non-alcoholic fatty liver disease group than the other groups (p&amp;lt;0.001). Hepatic artery resistive index was higher in children without non-alcoholic fatty liver disease group than children with non-alcoholic fatty liver disease group (0.64±0.1 and 0.60±0.1, respectively) (p=0.03), whereas hepatic artery resistive index was found to be close in children with non-alcoholic fatty liver disease and controls. These findings were similar to the differences in hepatic vascular changes observed during the development of non-alcoholic fatty liver disease, which were described in physio-pathological studies.Conclusion: Portal vein diameter, portal blood flow volume and hepatic artery resistive index values in obese children show significant differences according to the presence or absence of fatty liver. These differences are consistent with hepatic physio-pathological changes in non-alcoholic fatty liver disease. Therefore, hepatic vascular Doppler indices may be a new tool that can be used to monitor the development and progression of non-alcoholic fatty liver disease in obese children.

Advances in relationship between cell senescence and atherosclerosis.

Cellular senescence is a biological process associated with the degeneration of cell structure and function, which contribute to age-related diseases. Atherosclerosis is a chronic inflammatory disease that can cause a variety of cardiovascular disorders. In this article, we review the effects of cellular senescence on the development of atherosclerosis through diverse physiopathological changes, focusing on the alterations in senescent organelles and the increased senescence-associated secretory phenotype (SASP), and exploring the relevant therapeutic strategies for atherosclerosis by clearing senescent cells and reducing SASP, to provide new insights for the treatment of atherosclerosis.