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Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 4066
Author(s):  
Arleta Dołowacka-Jóźwiak ◽  
Adam Matkowski ◽  
Izabela Nawrot-Hadzik

Hyperglycemia, when sustained over a long time in diabetes mellitus (DM), leads to biochemical and cellular abnormalities, primarily through the formation of advanced glycation end-products (AGEs). In the treatment of diabetes, beside blood-sugar-lowering medications, a consumption of herbal products that can inhibit the AGEs’ formation is recommended. This study investigated the in vitro antiglycoxidative potential of extracts and fractions from the rhizomes of Japanese, Giant, and Bohemian knotweeds (Reynoutria japonica (Houtt.), R. sachalinensis (F. Schmidt) Nakai, and R.× bohemica Chrtek et Chrtkova). Their effects on glycooxidation of bovine and human serum albumin were evaluated by incubation of the proteins with a mixture of glucose and fructose (0.5 M) and 150 µg/mL of extract for 28 days at 37 °C, followed by measuring early and late glycation products, albumin oxidation (carbonyl and free thiol groups), and amyloid-β aggregation (thioflavin T and Congo red assays). The highest antiglycoxidative activity, comparable or stronger than the reference drug (aminoguanidine), was observed for ethyl acetate and diethyl ether fractions, enriched in polyphenols (stilbenes, phenylpropanoid disaccharide esters, and free and oligomeric flavan-3-ols). In conclusion, the antiglycoxidative compounds from these three species should be further studied for potential use in the prevention and complementary treatment of DM.


2021 ◽  
Vol 11 (21) ◽  
pp. 10478
Author(s):  
Sunil Sharma ◽  
Owias Iqbal Dar ◽  
Megha Andotra ◽  
Simran Sharma ◽  
Arvinder Kaur ◽  
...  

Xenobiotic Triclosan (TCS) is of great concern because of its existence in a variety of personal, household and healthcare products and continuous discharge in water worldwide. Excessive use of TCS-containing sanitizers and antiseptic products during the COVID-19 pandemic further increased its content in aquatic ecosystems. The present study deals with the cyto-genotoxic effects and biochemical alterations in the hatchlings of Labeo rohita on exposure to environmentally relevant concentrations of TCS. Three-days-old hatchlings were exposed to tap water, acetone (solvent control) and 4 environmentally relevant concentrations (6.3, 12.6, 25.2 and 60 µg/L) of TCS for 14 days and kept for a recovery period of 10 days. The significant concentration-dependent decline in cell viability but increase in micronucleated cells, nucleo-cellular abnormalities (NCAs) and DNA damage parameters like tail length, tail moment, olive tail moment and percent of tail DNA after exposure persisted till the end of recovery period. Glucose, triglycerides, cholesterol, total protein, albumin, total bilirubin, uric acid and urea (except for an increase at 60 µg/L) showed significant (p ≤ 0.05) concentration-dependent decrease after 14 days of exposure. The same trend (except for triglycerides, albumin and total bilirubin) continued till 10 days post exposure. In comparison to control, transaminases (alanine and aspartate aminotransferases) increased (p ≤ 0.05) after exposure as well as the recovery period, while a decline in alkaline phosphatase after exposure was followed by a significant increase during the recovery period. The results show that the environmentally relevant concentrations of TCS cause deleterious effects on the hatchlings of L. rohita.


Author(s):  
Sandra Jacinto ◽  
Patrícia Guerreiro ◽  
Rita Machado de Oliveira ◽  
Teresa Cunha-Oliveira ◽  
Maria João Santos ◽  
...  

Mutations in the MPV17 gene are associated with hepatocerebral form of mitochondrial depletion syndrome. The mechanisms through which MPV17 mutations cause respiratory chain dysfunction and mtDNA depletion is still unclear. The MPV17 gene encodes an inner membrane mitochondrial protein that was recently described to function as a non-selective channel. Although its exact function is unknown, it is thought to be important in the maintenance of mitochondrial membrane potential (ΔΨm). To obtain more information about the role of MPV17 in human disease, we investigated the effect of MPV17 knockdown and of selected known MPV17 mutations associated with MPV17 disease in vitro. We used different approaches in order to evaluate the cellular consequences of MPV17 deficiency. We found that lower levels of MPV17 were associated with impaired mitochondrial respiration and with a quiescent energetic metabolic profile. All the mutations studied destabilized the protein, resulting in reduced protein levels. We also demonstrated that different mutations caused different cellular abnormalities, including increased ROS production, decreased oxygen consumption, loss of ΔΨm, and mislocalization of MPV17 protein. Our study provides novel insight into the molecular effects of MPV17 mutations and opens novel possibilities for testing therapeutic strategies for a devastating group of disorders.


2021 ◽  
Author(s):  
Laura Bergamaschi ◽  
Federica Mescia ◽  
Lorinda Turner ◽  
Aimee Hanson ◽  
Prasanti Kotagiri ◽  
...  

SummaryIn a study of 207 SARS-CoV2-infected individuals with a range of severities followed over 12 weeks from symptom onset, we demonstrate that an early robust immune response, without systemic inflammation, is characteristic of asymptomatic or mild disease. Those presenting to hospital had delayed adaptive responses and systemic inflammation already evident at around symptom onset. Such early evidence of inflammation suggests immunopathology may be inevitable in some individuals, or that preventative intervention might be needed before symptom onset. Viral load does not correlate with the development of this pathological response, but does with its subsequent severity. Immune recovery is complex, with profound persistent cellular abnormalities correlating with a change in the nature of the inflammatory response, where signatures characteristic of increased oxidative phosphorylation and reactive-oxygen species-associated inflammation replace those driven by TNF and IL-6. These late immunometabolic inflammatory changes and unresolved immune cell defects, if persistent, may contribute to “long COVID”.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mojgan Padash Barmchi ◽  
Miranda Thomas ◽  
Jayashree V. Thatte ◽  
Arushi Vats ◽  
Bing Zhang ◽  
...  

AbstractHuman papillomavirus (HPV) is the leading cause of cervical cancer and has been implicated in several other cancer types including vaginal, vulvar, penile, and oropharyngeal cancers. Despite the recent availability of a vaccine, there are still over 310,000 deaths each year worldwide. Current treatments for HPV-mediated cancers show limited efficacy, and would benefit from improved understanding of disease mechanisms. Recently, we developed a Drosophila ‘HPV 18 E6’ model that displayed loss of cellular morphology and polarity, junctional disorganization, and degradation of the major E6 target Magi; we further provided evidence that mechanisms underlying HPV E6-induced cellular abnormalities are conserved between humans and flies. Here, we report a functional genetic screen of the Drosophila kinome that identified IKK$$\beta$$ β —a regulator of NF-κB—as an enhancer of E6-induced cellular defects. We demonstrate that inhibition of IKK$$\beta$$ β reduces Magi degradation and that this effect correlates with hyperphosphorylation of E6. Further, the reduction in IKK$$\beta$$ β suppressed the cellular transformation caused by the cooperative action of HPVE6 and the oncogenic Ras. Finally, we demonstrate that the interaction between IKK$$\beta$$ β and E6 is conserved in human cells: inhibition of IKK$$\beta$$ β blocked the growth of cervical cancer cells, suggesting that IKK$$\beta$$ β may serve as a novel therapeutic target for HPV-mediated cancers.


2020 ◽  
Vol 11 ◽  
Author(s):  
Paavali A. Hannikainen ◽  
Peter Kosa ◽  
Christopher Barbour ◽  
Bibiana Bielekova

Quantifying cell subpopulations in biological fluids aids in diagnosis and understanding of the mechanisms of injury. Although much has been learned from cerebrospinal fluid (CSF) flow cytometry in neuroimmunological disorders, such as multiple sclerosis (MS), previous studies did not contain enough healthy donors (HD) to derive age- and gender-related normative data and sufficient heterogeneity of other inflammatory neurological disease (OIND) controls to identify MS specific changes.The goals of this blinded training and validation study of MS patients and embedded controls, representing 1,240 prospectively acquired paired CSF/blood samples from 588 subjects was (1) to define physiological age-/gender-related changes in CSF cells, (2) to define/validate cellular abnormalities in blood and CSF of untreated MS through disease duration (DD) and determine which are MS-specific, and (3) to compare effect(s) of low-efficacy (i.e., interferon-beta [IFN-beta] and glatiramer acetate [GA]) and high-efficacy drugs (i.e., natalizumab, daclizumab, and ocrelizumab) on MS-related cellular abnormalities using propensity score matching.Physiological gender differences are less pronounced in the CSF compared to blood, and age-related changes suggest decreased immunosurveillance of CNS by activated HLA-DR+T cells associated with natural aging. Results from patient samples support the concept of MS being immunologically single disease evolving in time. Initially, peripherally activated innate and adaptive immune cells migrate into CSF to form MS lesions. With progression, T cells (CD8+ > CD4+), NK cells, and myeloid dendritic cells are depleted from blood as they continue to accumulate, together with B cells, in the CSF and migrate to CNS tissue, forming compartmentalized inflammation. All MS drugs inhibit non-physiological accumulation of immune cells in the CSF. Although low-efficacy drugs tend to normalize it, high-efficacy drugs overshoot some aspects of CSF physiology, suggesting impairment of CNS immunosurveillance. Comparable inhibition of MS-related CSF abnormalities advocates changes within CNS parenchyma responsible for differences in drug efficacy on MS disability progression.Video summarizing all results may become useful educational tool.


2020 ◽  
Vol 11 ◽  
Author(s):  
Md. Shahjahan ◽  
Most. Sabia Khatun ◽  
Mim Mostarin Mun ◽  
S. M. Majharul Islam ◽  
Md. Helal Uddin ◽  
...  

2020 ◽  
Author(s):  
Paavali A. Hannikainen ◽  
Peter Kosa ◽  
Christopher Barbour ◽  
Bibiana Bielekova

AbstractQuantifying cell subpopulations in biological fluids aids in diagnosis and understanding of the mechanisms of injury. Although much has been learned from cerebrospinal fluid (CSF) flow cytometry in neuroimmunological disorders such as multiple sclerosis (MS), previous studies did not contain enough healthy donors (HD) to derive age- and gender-related normative data and sufficient heterogeneity of other inflammatory neurological diseases (OIND) controls to identify MS specific changes.The goals of this blinded, training and validation study of MS patients and embedded controls, representing 1240 prospectively-acquired paired CSF/blood samples from 588 subjects was: 1. To define physiological age/gender-related changes in CSF cells; 2. To define/validate cellular abnormalities in blood and CSF of untreated MS through disease duration (DD) and determine which are MS-specific; 3. To compare effect(s) of low-efficacy (i.e., interferon-beta [IFN-beta] and glatiramer acetate [GA]) and high-efficacy drugs (i.e., natalizumab, daclizumab and ocrelizumab) on MS-related cellular abnormalities using propensity score matching.Physiological gender differences are less pronounced in the CSF compared to blood, while age- related changes suggest decreased immunosurveillance of CNS by activated, HLA-DR+ T cells associated with natural aging. Results from patient samples support concept of MS being immunologically single disease evolving in time. Initially, peripherally activated innate and adaptive immune cells migrate into CSF to form MS lesions. With progression, T cells (CD8+ > CD4+), NK cells and myeloid dendritic cells are depleted from blood as they continue to accumulate, together with B cells, in the CSF and migrate to CNS tissue forming compartmentalized inflammation. All MS drugs inhibit non-physiological accumulation of immune cells in the CSF. While low efficacy drugs tend to normalize it, high efficacy drugs overshoot some aspects of CSF physiology suggesting impairment of CNS immunosurveillance. Comparable inhibition of MS-related CSF abnormalities advocates changes within CNS parenchyma responsible for differences in drug’s efficacy on MS disability progression.Video summarizing all results may become useful educational tool.


F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 208
Author(s):  
Sarah Moustafa ◽  
Steven Young

Recurrent implantation failure (RIF) is an uncommon, imprecisely defined clinical disorder characterized by failure to achieve pregnancy after repeated embryo transfers. The diverse etiologies and incomplete understanding of RIF provide significant diagnostic and therapeutic challenges to patients and providers. Careful clinical evaluation prior to assisted reproduction can uncover many treatable causes, including thyroid dysfunction, submucosal myomas, and tobacco use. The more-subtle causes often require a more-targeted assessment. Undetected, small polyps or small areas of intrauterine synechiae are relatively common and easily treated contributors to RIF. Molecular and cellular abnormalities pose a greater therapeutic challenge. Putative causes of RIF, including progesterone resistance, shifted window of receptivity, decreased integrin expression, and immunologic disturbances, should be considered in the evaluation of a patient with otherwise unexplained RIF. It may also be true that a more complex and standardized definition of RIF would be helpful in these cases. In this paper, we review the diagnostic and therapeutic approaches to RIF, with emphasis on disorders of endometrial receptivity.


2019 ◽  
Vol 19 (1) ◽  
pp. 49-60 ◽  
Author(s):  
Ashwani K. Singal ◽  
Shannon M. Bailey

Alcohol-associated liver disease (AALD) is the third most common preventable cause for disease burden and mortality in the US. AALD, including alcoholic hepatitis (AH), contributes to half of admissions from decompensated liver disease and 20% of all liver transplants in the US. Peripheral blood cells contribute to systemic inflammation, oxidative stress, mitochondrial dysfunction, and fibrosis in AALD and AH. Alcohol dysregulates function of lymphocytes, neutrophils, monocytes, and tissue macrophages of the innate immune system. These alterations in turn can modulate adaptive immune responses. In this review, we describe these disruptive effects of alcohol on cells of the innate and adaptive immune system and focus on cellular-based emerging biomarkers on diagnosis and prognosis of patients with AALD and AH.


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