Cerebral White Matter Alterations Associated With Oligodendrocyte Vulnerability in Organic Acidurias: Insights in Glutaric Aciduria Type I.

The white matter is an important constituent of the central nervous system, containing axons, oligodendrocytes, and its progenitor cells, astrocytes, and microglial cells. Oligodendrocytes are central for myelin synthesis, the insulating envelope that protects axons and allows normal neural conduction. Both, oligodendrocytes and myelin, are highly vulnerable to toxic factors in many neurodevelopmental and neurodegenerative disorders associated with disturbances of myelination. Here we review the main alterations in oligodendrocytes and myelin observed in some organic acidurias/acidemias, which correspond to inherited neurometabolic disorders biochemically characterized by accumulation of potentially neurotoxic organic acids and their derivatives. The yet incompletely understood mechanisms underlying the high vulnerability of OLs and/or myelin in glutaric acidemia type I, the most prototypical cerebral organic aciduria, are particularly discussed.

Relationship between nailfold capillaroscopy findings and the etiology and prognosis of interstitial lung disease.

OBJECTIVES: Connective tissue-associated interstitial lung diseases (CTD-ILD) are believed to be caused by microvascular damage. The objective of this study was to assess the nailfold capillaroscopy (NFC) pattern in patients diagnosed with both CTD-ILD and non-CTD-ILD to identify microvascular changes and determine the relation between capillaroscopic parameters, clinical variables, and disease-related measurements. PATIENTS AND METHODS: This cross-sectional study included 95 patients with interstitial lung disease who applied to our Rheumatology and Chest Clinics between September 2021 and July 2023. The patients were divided into two groups based on their diagnosis: non-CTD-ILD (group 1) and CTD-ILD (group 2). Nailfold capillaroscopy was performed. RESULTS: Ninety-five patients, 49 (51% female, mean age 62.31 ± 11.027 years) in group 1 and 46 (69.6% female, mean age 62.09 ± 10.887 years) in group 2, were included in the study. Abnormal capillary morphologies were both detected in the CTD-ILD group and the non-CTD-ILD groups. In patients with a usual interstitial pneumonia (UIP) pattern on chest computed tomography (CT), tortuosity was higher than in patients with non-specific interstitial pneumonia (NSIP) (P = 0.041), and the proportion of tortuosity increased significantly as the duration of the disease increased (P = 0.016). CONCLUSION: Our study highlights capillaroscopic abnormalities alone may not be sufficient to differentiate CTD-ILD (other than systemic sclerosis) from non-CTD-ILD. The presence of NFC abnormalities in non-CTD-ILD may suggest that fibrotic lung disease could potentially play a role in the deterioration of the microvascular structure or abnormal angiogenesis. Our study demonstrated that a multidisciplinary approach, incorporating clinical, morphological, pathological, and serological evaluations, is necessary for interpreting ILD. Key Points • Capillaroscopic abnormalities can also be seen in non-CTD-ILD. • Capillaroscopy findings do not distinguish the non-Ssc etiology of ILD. • Nailfold capillaroscopy may have the potential to serve as a useful tool in predicting prognosis and monitoring the disease progression in patients with idiopathic pulmonary fibrosis (IPF).

Association between augmented levels of the gut pro-hormone Proneurotensin and subclinical vascular damage.

Elevated levels of the gut pro-hormone Proneurotensin (proNT) have been found to predict development of cardiovascular disease. However, it is still unknown whether higher proNT levels are associated with subclinical vascular damage. Herein, we investigated the relationship between higher proNT concentrations and augmented pulse pressure (PP) and carotid intima-media thickness (cIMT), indicators of increased arterial stiffness and subclinical atherosclerosis, respectively. Clinical characteristics, PP and cIMT were evaluated in 154 non-diabetic individuals stratified into tertiles according to fasting serum proNT concentrations. We found that, subjects with higher proNT levels exhibited a worse lipid profile and insulin sensitivity, increased C-reactive protein levels, along with higher values of PP and cIMT as compared to the lowest proNT tertile. Prevalence of elevated PP (≥ 60 mmHg) and subclinical carotid atherosclerosis (IMT > 0.9 mm) was increased in the highest tertile of proNT. In a logistic regression analysis adjusted for several confounders, subjects with higher proNT levels displayed a fivefold raised risk of having elevated PP values (OR 5.36; 95%CI 1.04-27.28; P = 0.05) and early carotid atherosclerosis (OR 4.81; 95%CI 1.39-16.57; P = 0.01) as compared to the lowest proNT tertile. In conclusion, higher circulating levels of proNT are a biomarker of subclinical vascular damage independent of other atherosclerotic risk factors.

Effect of true triaxial principal stress unloading rate on strain energy density of sandstone.

Deep rock are often in a true triaxial stress state. Studying the impacts of varying unloading speeds on their strain energy (SE) density is highly significant for predicting rock stability. Through true triaxial unloading principal stress experiments and true triaxial stress equilibrium unloading experiments on sandstone, this paper proposes a method to compute the SE density in a true triaxial compressive unloading principal stress test. This method aims to analyze the SE variation in rocks under the action of true triaxial unloading principal stresses. Acoustic emission is used to verify the correctness of the SE density calculation method in this paper. This study found that: (1) Unloading in one principal stress direction causes the SE density to rise in the other principal stress directions. This rise in SE, depending on its reversibility, can be categorized into elastic and dissipated SE. (2)When unloading principal stresses, the released elastic SE density in the unloading direction is influence by the stress path and rate. (3) The higher the unloading speed will leads to greater increases in the input SE density, elastic SE density, and dissipative SE density in the other principal stress directions. (4) The dissipated SE generated under true triaxial compression by unloading the principal stress is positively correlated with the damage to the rock; with an increase in unloading rate, there is a corresponding increase in the formation of cracks after unloading. (5) Utilizing the stress balance unloading test, we propose a calculation method for SE density in true triaxial unloading principal stress tests.

Common double-lumen tube selection methods overestimate adequate tube sizes in individual patients - a 3D reconstruction study.

BACKGROUND: Appropriate selection of double-lumen tube sizes for one-lung ventilation is crucial to prevent airway damage. Current selection methods rely on demographic factors or 2D radiography. Prediction of left bronchial diameter is indispensable for choosing the adequate tube size. This prospective observational study investigates if current selection methods sufficiently predict individuals' left bronchial diameters for DLT selection compared to the 3D reconstruction. METHODS: 100 patients necessitating thoracic surgery with one-lung ventilation and left-sided double-lumen tubes, ≥ 18 years of age, and a set of chest X-rays and 2D thorax CT scans for 3D reconstruction of the left main bronchus were included between 07/2021 and 06/2023. The cross-validated prediction error and the width of the 95%-prediction intervals of the 3D left main bronchial diameter utilizing linear prediction models were based on current selection methods. RESULTS: The mean bronchial diameter in 3D reconstruction was 13.6 ± 2.1 mm. The ranges of the 95%-prediction intervals for the bronchial diameter were 6.4 mm for demographic variables, 8.3 mm for the tracheal diameter from the X-ray, and 5.9 mm for bronchial diameter from the 2D-CT scans. Current methods violated the suggested '≥1 mm' safety criterion in up to 7% (men) and 42% (women). Particularly, 2D radiography overestimated women's left bronchial diameter. Current methods even allowed the selection of double-lumen tubes with bronchial tube sections greater than the bronchial diameter in women. CONCLUSIONS: Neither demographic nor 2D-radiographic methods sufficiently account for the variability of the bronchial diameter. Wide 95%-prediction intervals for the bronchial diameter hamper accurate individual double-lumen tube selection. This increases women's risk of bronchial damage, particularly if they have other predisposing factors. These patients may benefit from 3D reconstruction of the left main bronchus. TRIAL REGISTRATION: Not applicable.

Pre-exercise cryotherapy reduces myoglobin and creatine kinase levels after eccentric muscle stress in young women.

Introduction: The aim of this study was to investigate the effect of pre-exercise whole-body cryotherapy (WBC) on muscle damage indicators following eccentric treadmill exercise in young women. Methods: Twenty-seven participants underwent two 1-h downhill treadmill runs, replicating 60% of their maximal oxygen uptake, with a 4-week intermission for recovery and treatment application. In this intermission, one group underwent 20 sessions of WBC, delivered five times a week at -120°C for 3 min each, while the comparison group received no such treatment. Markers of muscle injury-serum myoglobin concentration, creatine kinase and lactate dehydrogenase activity and also uric acid, and cell-free DNA concentration-were measured before and after downhill runs. Results: The study observed a notable reduction in post-exercise myoglobin and CK levels in the WBC group after the second running session. Discussion: The results suggest that WBC can have a protective effects against muscle damage resulting from eccentric exercise.

Assessing genotoxic effects of chemotherapy agents by a robust in vitro assay based on mass spectrometric quantification of γ-H2AX in HepG2 cells.

Chemotherapy has already proven widely effective in treating cancer. Chemotherapeutic agents usually include DNA damaging agents and non-DNA damaging agents. Assessing genotoxic effect is significant during chemotherapy drug development, since the ability to attack DNA is the major concern for DNA damaging agents which relates to the therapeutic effect, meanwhile genotoxicity should also be evaluated for chemotherapy agents' safety especially for non-DNA damaging agents. However, currently applicability of in vitro genotoxicity assays is hampered by the fact that genotoxicity results have comparatively high false positive rates. γ-H2AX has been shown to be a bifunctional biomarker reflecting both DNA damage response and repair. Previously, we developed an in vitro genotoxicity assay based on γ-H2AX quantification using mass spectrometry. Here, we employed the assay to quantitatively assess the genotoxic effects of 34 classic chemotherapy agents in HepG2 cells. Results demonstrated that the evaluation of cellular γ-H2AX could be an effective approach to screen and distinguish types of action of different classes of chemotherapy agents. In addition, two crucial indexes of DNA repair kinetic curve, i.e., k (speed of γ-H2AX descending) and t50 (time required for γ-H2AX to drop to half of the maximum value) estimated by our developed online tools were employed to further evaluate nine representative chemotherapy agents, which showed a close association with therapeutic index or carcinogenic level. The present study demonstrated that mass spectrometric quantification of γ-H2AX may be an appropriate tool to preliminarily evaluate genotoxic effects of chemotherapy agents.

Association between synovial tissue damage and pain in late-stage knee osteoarthritis: A cross-sectional study.

OBJECTIVE: To identify the presence and distribution of histopathological features of synovial inflammation and tissue damage, and to test their associations with ultrasound (US) imaging measures of synovitis and patient-reported measures of pain in knee osteoarthritis (OA). DESIGN: In the cross-sectional study of 122 patients undergoing surgery for painful late-stage (Kellgren-Lawrence Grade 3 or 4) knee OA, we compared US measures of synovitis (n = 118) and pain (Knee Injury and Osteoarthritis Outcome Score) to histopathological measures of inflammation vs. synovial tissue damage in synovial tissue biopsies. Associations of histopathological features with US measures of inflammation or pain were assessed using linear or logistic regression while controlling for covariates. RESULTS: Histopathological features of inflammation were associated with higher odds of moderate/severe US synovitis (odds ratio [OR] = 1.34 [95%CI 1.04, 1.74), whereas features of synovial tissue damage were associated with lower odds of moderate/severe US synovitis (OR = 0.77 [95%CI 0.57, 1.03]). Worse histopathological scores for synovial tissue damage were associated with more pain (-1.47 [95%CI -2.88, -0.05]), even while adjusting for synovial inflammation (-1.61 [95%CI -3.12, -0.10]). CONCLUSIONS: Synovial tissue damage is associated with pain in late-stage knee OA, independent from inflammation and radiographic damage. These novel findings suggest that preventing synovial tissue damage may be an important goal of disease-modifying OA therapy.

Damage evolution law of multi-hole blasting igneous rock and quantitative evaluation model of damage degree based on fractal theory and clustering algorithm.

The geological phenomenon of igneous rock invading coal seam is widely distributed, which induces mining risk and affects efficient mining. The pre-splitting blasting method of igneous rock is feasible but difficult to implement accurately, resulting in unnecessary safety and environmental pollution risks. In this paper, the blasting model with penetrating structural plane and the multi-hole blasting model with different hole spacing were established based on the Riedel-Hiermaier-Thoma (RHT) damage constitutive to explore the stress wave propagation law under detonation. The damage cloud diagram and damage degree algorithm were used to quantitatively describe the spatio-temporal evolution of blasting damage. The results show that the explosion stress wave presents a significant reflection stretching effect under the action of the structural plane, which can effectively aggravate the presplitting blasting degree of the rock mass inside the structural plane. The damage range of rock mass is synchronously evolved with the change of blasting hole spacing. The blasting in the igneous rock intrusion area of the 21,914 working face is taken as an application example, and the damage degree of rock mass is reasonably evaluated by the box-counting dimension and K-means clustering method, which proves the effectiveness of the blasting scheme and provides reference value for the implementation of related blasting projects.

Complication detection in MRI guided cardiac ablation: Atrial wall damage and hepatic oedema.

Magnetic resonance imaging is a novel imaging technique for guiding electrophysiology based ablation operations for atrial flutter and typical atrial fibrillation. When compared to standard electrophysiology ablation, this innovative method allows for better outcomes. Intra-procedural imaging is important for following the catheter in real time throughout the ablation operation while also seeing cardiac architecture and determining whether the ablation is being completed appropriately utilizing oedema sequences. At the same time, intra-procedural imaging allows immediate visualization of any complications of the procedure. We describe a case of a 67 year old male underwent an isthmus-cavo-tricuspid magnetic resonance-guided thermoablation procedure for atrial flutter episodes. During the procedure we noted an atypical focal thinning of the right atrial wall at the isthmus cava-tricuspidal zone. The post-procedural Black Blood T2 STIR showed an area of hyperintensity at the hepatic dome and glissonian capsule, which was consistent with intraparenchymal hepatic oedema, in close proximity to the atrial finding. Given the opportunity to direct monitoring of adjacent tissues, we aim to highlight with our case the ability of magnetic resonance-guided cardiac ablation to immediately detect peri-procedural complications in the ablative treatment of atrial fibrillation.

Pathological mechanism of immune disorders in diabetic kidney disease and intervention strategies.

Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease. Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes. With the development of immunological technology, many studies have shown that diabetic nephropathy is an immune complex disease, and that most patients have immune dysfunction. However, the immune response associated with diabetic nephropathy and autoimmune kidney disease, or caused by ischemia or infection with acute renal injury, is different, and has a com-plicated pathological mechanism. In this review, we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism, to provide guidance and advice for early intervention and treatment of diabetic nephropathy.

Advancements in understanding the role of ferroptosis in hypoxia-associated brain injury: a narrative review.

Background and Objective: Ferroptosis, a form of programmed cell death driven by lipid peroxidation and dependent on iron ions, unfolds through a sophisticated interplay of multiple biological processes. These include perturbations in iron metabolism, lipid peroxidation, aberrant amino acid metabolism, disruptions in hypoxia-inducible factor-prolyl hydroxylase (HIF-PHD) axis, and endoplasmic reticulum (ER) stress. Recent studies indicate that ferroptosis may serve as a promising therapeutic target for hypoxia-associated brain injury such as hypoxic-ischemic brain damage (HIBD) and cerebral ischemia-reperfusion injury (CIRI). HIBD is a neonatal disease that can be fatal, causing death or mental retardation in newborns. HIBD is a kind of diffuse brain injury, which is characterized by apoptosis of nerve cells and abnormal function and structure of neurons after cerebral hypoxia and ischemia. At present, there are no fundamental prevention and treatment measures for HIBD. The brain is the most sensitive organ of the human body to hypoxia. Cerebral ischemia will lead to the damage of local brain tissue and its function, and CIRI will lead to a series of serious consequences. We hope to clarify the mechanism of ferroptosis in hypoxia-associated brain injury, inhibit the relevant targets of ferroptosis in hypoxia-associated brain injury to guide clinical treatment, and provide guidance for the subsequent treatment of disease-related drugs. Methods: Our research incorporated data on "ferroptosis", "neonatal hypoxic ischemia", "hypoxic ischemic brain injury", "hypoxic ischemic encephalopathy", "brain ischemia-reperfusion injury", and "therapeutics", which were sourced from Web of Science, PubMed, and comprehensive reviews and articles written in English. Key Content and Findings: This review delineates the underlying mechanisms of ferroptosis and the significance of these pathways in hypoxia-associated brain injury, offering an overview of therapeutic strategies for mitigating ferroptosis. Conclusions: Ferroptosis involves dysregulation of iron metabolism, lipid peroxidation, amino acid metabolism, dysregulation of HIF-PHD axis and endoplasmic reticulum stress (ERS). By reviewing the literature, we identified the involvement of the above processes in HIBD and CIRI, and summarized a series of therapeutic measures for HIBD and CIRI by inhibiting ferroptosis. We hope this study would provide guidance for the clinical treatment of HIBD and CIRI in the future.

Chemotherapy's effects on autophagy in the treatment of Hodgkin's lymphoma: a scoping review.

BACKGROUND: Classical Hodgkin Lymphomas (HL) are a unique malignant growth with an excellent initial prognosis. However, 10-30% of patients will still relapse after remission. One primary cellular function that has been the focus of tumor progression is autophagy. This process can preserve cellular homeostasis under stressful conditions. Several studies have shown that autophagy may play a role in developing HL. Therefore, this review aimed to explore chemotherapy's effect on autophagy in HL, and the effects of autophagy on HL. METHODS: A scoping review in line with the published PRISMA extension for scoping reviews (PRISMA-ScR) was conducted. A literature search was conducted on the MEDLINE database and the Cochrane Central Register of Controlled Trials (CENTRAL). All results were retrieved and screened, and the resulting articles were synthesized narratively. RESULTS: The results showed that some cancer chemotherapy also induces autophagic flux. Although the data on HL is limited, since the mechanisms of action of these drugs are similar, we can infer a similar relationship. However, this increased autophagy activity may reflect a mechanism for increasing tumor growth or a cellular compensation to inhibit its growth. Although evidence supports both views, we argued that autophagy allowed cancer cells to resist cell death, mainly due to DNA damage caused by cytotoxic drugs. CONCLUSION: Autophagy reflects the cell's adaptation to survive and explains why chemotherapy generally induces autophagy functions. However, further research on autophagy inhibition is needed as it presents a viable treatment strategy, especially against drug-resistant populations that may arise from HL chemotherapy regimens.

Phylloquinone improves endothelial function, inhibits cellular senescence, and vascular inflammation.

Phylloquinon (PK) and menaquinones (MK) are both naturally occurring compounds belonging to vitamin K group. Present study aimed to comprehensively analyze the influence of PK in several models of vascular dysfunction to determine whether PK has vasoprotective properties, similar to those previously described for MK. Effects of PK and MK on endothelial dysfunction were studied in ApoE/LDLR-/- mice in vivo, in the isolated aorta incubated with TNF, and in vascular cells as regard inflammation and cell senescence (including replicative and stress-induced models of senescence). Moreover, the vascular conversion of exogenous vitamins to endogenous MK-4 was analyzed. PK, as well as MK, given for 8 weeks in diet (10 mg/kg) resulted in comparable improvement in endothelial function in the ApoE/LDLR-/- mice. Similarly, PK and MK prevented TNF-induced impairment of endothelium-dependent vasorelaxation in the isolated aorta. In in vitro studies in endothelial and vascular smooth muscle cells, we identified that both PK and MK displayed anti-senescence effects via decreasing DNA damage while in endothelial cells anti-inflammatory activity was ascribed to the modulation of NFκB activation. The activity of PK and MK was comparable in terms of their effect on senescence and inflammation. Presence of endogenous synthesis of MK-4 from PK in aorta and endothelial and smooth muscle cells suggests a possible involvement of MK in vascular effects of PK. In conclusion, PK and MK display comparable vasoprotective effects, which may be ascribed, at least in part, to the inhibition of cell senescence and inflammation. The vasoprotective effect of PK in the vessel wall can be related to the direct effects of PK, as well as to the action of MK formed from PK in the vascular wall.

Unlocking the Potential of Ultra-High Dose Fractionated Radiation for Effective Treatment of Glioblastoma in Mice.

Background: Current radiotherapy regimens for glioblastoma (GBM) have limited efficacy and fails to eradicate tumors. Regenerative medicine brings hope for repairing damaged tissue, opening opportunities for elevating the maximum acceptable radiation dose. In this study, we explored the effect of ultra-high dose fractionated radiation on tumor responses and brain injury in immunocompetent mice which can better mimic the tumor-host interactions observed in patients. We also evaluated the role of the hypoxia-inducible factor-1 alpha under radiation as potential target for combating radiation-induced brain injury. Methods: Naïve and Hif-1α+/- heterozygous mice received a fractionated daily dose of 20 Gy for three or five consecutive days. Magnetic resonance imaging (MRI) and histology were performed to assess brain injury post-radiation. The 2×105 human GBM1 luciferase-expressing cells were transplanted with tolerance induction protocol. Fractionated radiotherapy was performed during the exponential phase of tumor growth. Bioluminescence imaging, MRI, and immunohistochemistry staining were performed to evaluate tumor growth dynamics and radiotherapy responses. Additionally, animal lifespan was recorded. Results: Fractionated radiation of 5×20 Gy induced severe brain damage, starting 3 weeks after radiation. All animals from this group died within 12 weeks. In contrast, later onset and less severe brain injury were observed starting 12 weeks after radiation of 3×20 Gy. It resulted in complete GBM eradication and survival of all treated animals. Furthermore, Hif-1α+/- mice exhibited more severe vascular damage after fractionated radiation of 3×20 Gy. Conclusion: Ultra-high dose fractionated 3×20 Gy radiation has the potential to fully eradicate GBM cells at the cost of only mild brain injury. The Hif-1α gene is a promising target for ameliorating vascular impairment post-radiation, encouraging the implementation of neurorestorative strategies.

Traction-separation law parameters for the description of age-related changes in the delamination strength of the human descending thoracic aorta.

Aortic dissection is a life-threatening disease that consists in the development of a tear in the wall of the aorta. The initial tear propagates as a discontinuity leading to separation within the aortic wall, which can result in the creation of a so-called false lumen. A fatal threat occurs if the rupture extends through the whole thickness of the aortic wall, as blood may then leak. It is generally accepted that the dissection, which can sometime extend along the entire length of the aorta, propagates via a delamination mechanism. The aim of the present paper is to provide experimentally validated parameters of a mathematical model for the description of the wall's cohesion. A model of the peeling experiment was built in Abaqus. The delamination interface was described by a piecewise linear traction-separation law. The bulk behavior of the aorta was assumed to be nonlinearly elastic, anisotropic, and incompressible. Our simulations resulted in estimates of the material parameters for the traction-separation law of the human descending thoracic aorta, which were obtained by minimizing the differences between the FEM predictions and the delamination force given by the regression of the peeling experiments. The results show that the stress at damage initiation, Tc, should be understood as an age-dependent quantity, and under the assumptions of our model this dependence can be expressed by linear regression as Tc = - 13.03·10-4·Age + 0.2485 if the crack front advances in the axial direction, and Tc = - 7.58·10-4·Age + 0.1897 if the crack front advances in the direction of the aortic circumference (Tc [MPa], Age [years]). Other model parameters were the stiffness K and the separation at failure, δf-δc (K = 0.5 MPa/mm, δf-δc = 0.1 mm). The material parameters provided by our study can be used in numerical simulations of the biomechanics of dissection propagation through the aorta especially when age-associated phenomena are studied.

E3 ligases: a ubiquitous link between DNA repair, DNA replication and human disease.

Maintenance of genome stability is of paramount importance for the survival of an organism. However, genomic integrity is constantly being challenged by various endogenous and exogenous processes that damage DNA. Therefore, cells are heavily reliant on DNA repair pathways that have evolved to deal with every type of genotoxic insult that threatens to compromise genome stability. Notably, inherited mutations in genes encoding proteins involved in these protective pathways trigger the onset of disease that is driven by chromosome instability e.g. neurodevelopmental abnormalities, neurodegeneration, premature ageing, immunodeficiency and cancer development. The ability of cells to regulate the recruitment of specific DNA repair proteins to sites of DNA damage is extremely complex but is primarily mediated by protein post-translational modifications (PTMs). Ubiquitylation is one such PTM, which controls genome stability by regulating protein localisation, protein turnover, protein-protein interactions and intra-cellular signalling. Over the past two decades, numerous ubiquitin (Ub) E3 ligases have been identified to play a crucial role not only in the initiation of DNA replication and DNA damage repair but also in the efficient termination of these processes. In this review, we discuss our current understanding of how different Ub E3 ligases (RNF168, TRAIP, HUWE1, TRIP12, FANCL, BRCA1, RFWD3) function to regulate DNA repair and replication and the pathological consequences arising from inheriting deleterious mutations that compromise the Ub-dependent DNA damage response.

Aronia Melanocarpa Elliot Anthocyanins Inhibits Alcoholic Liver Disease by Activation of α7nAChR.

The study wanted to explore the preventative effects of Aornia melanocarpa Elliot anthocyanins (AMA) to Alcoholic liver disease (ALD) by bioinformatics prediction and experimental verification. We founded 419 differentially expressed genes (DEGs) in GSE28619 related to ALD from GEO database, COL1A1 was selected by the core gene module construction and molecular docking. Mice were treated by intragastric administration of gradient 50% ethanol, AMA alleviated liver injury by ALD and ameliorated the model's body weight, lessened the liver inflammation according to histopathological evaluation, increased serum liver biochemical index (AST, ALT, TC, TG and LDL-C) and decreased HDL-C, reversed the expression of enzymes (ALDH and GSH-PX), decreased cytokines expression (Ki67, TNF-α and IL-6), reversed the expression of α7nAChR and collagen I, downregulated the PI3K-Akt pathway and Keap1/HO-1 pathway (p-PI3K, PI3K, p-Akt, Akt, Keap1, Nrf2, HO-1,GSK-3ß and Bcl-2), indicated that α7nAChR and collagen I may be the AMA action targets.

Seabuckthorn pulp extract alleviates UV-B-induced skin photo-damage by significantly reducing oxidative stress-mediated endoplasmic reticulum stress and DNA Damage in human primary skin fibroblasts and Balb/c mice skin.

Skin homeostasis is predominantly compromised by exposure to UV-B irradiation, leading to several physiopathological processes at cellular and tissue levels that deteriorate skin function and integrity. The current study investigated the photo-protective role of seabuckthorn fruit pulp (SBT) extract against UV-B-induced damage in primary human skin fibroblasts (HDFs) and Balb/C mice skin. We subjected HDFs and Balb/C mice to UV-B irradiation and measured multiple cellular damage indicators. We found that UV-B-irradiated HDFs treated with SBT had a considerably greater survival rate than cells exposed to UV-B radiation alone. The UV-B irradiation-induced ROS generation led to the degradation of the extracellular matrix, inflammation, DNA damage, endoplasmic reticulum (ER) stress, and apoptosis. SBT treatment significantly reduced these manifestations. Topical application of SBT alleviated UV-B-induced epidermal thickening, leukocyte infiltration, and degradation of extracellular matrix in Balb/c mice skin. Based on our results, we conclude that SBT has the potential to be developed as a therapeutic/cosmetic remedy for the prevention of skin photo-damage.

Multi-biomarker approach reveals the effects of heavy metal bioaccumulation in the foundation species Prosopis laevigata (Fabaceae).

Mining is a major economic activity in many developing countries. However, it disturbs the environment, producing enormous quantities of waste, known as mine tailings, which can have deleterious environmental impact, due to their high heavy metals (HM) content. Often, foundation species that establish on mine tailings are good candidates to study the effects of HM bioaccumulation at different levels of biological organization. Prosopis laevigata is considered a HM hyperaccumulator which presents attributes of a foundation species (FS) and establishes naturally on mine tailings. We evaluated the bioaccumulation of Cu, Pb, and Zn in P. laevigata foliar tissue, the leaf micro- and macro-morphological characters, DNA damage, and population genetic effects. In total, 80 P. laevigata individuals (20/site) belonging to four populations: The individuals from both sites (exposed and reference) bioaccumulated HMs (Pb > Cu > Zn). However, in the exposed individuals, Pb and Cu bioaccumulation was significantly higher. Also, a significant effect of macro- and micro-morphological characters was registered, showing significantly lower values in individuals from the exposed sites. In addition, we found significant differences in genotoxic damage in P. laevigata individuals, between the exposed and reference sites. In contrast, for the micro-morphological characters, none of the analyzed metals had any influence. P. laevigata did not show significant differences in the genetic structure and diversity between exposed and reference populations. However, four haplotypes and four private alleles were found in the exposed populations. Since P. laevigata is a species that establishes naturally in polluted sites and bioaccumulates HM in its foliar tissues, the resulting genetic, individual and population effects have not been severe enough to show detrimental effects; hence, P. laevigata can be a useful tool in phytoremediation strategies for soils polluted with Pb and Cu, maintaining its important ecological functions.