Stress Function Research Articles

Stress, hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-gonadal axis, and aggression.

This comprehensive review explores the intricate relationship between the hypothalamic-pituitary-adrenal (HPA) axis, the hypothalamic-pituitary-gonadal (HPG) axis, and aggression. It provides a detailed overview of the physiology and functioning of these axes, as well as the implications for aggressive behavior. The HPA axis, responsible for the stress response, is activated in response to various stressors and can influence aggressive behavior. Glucocorticoids, such as cortisol, play a crucial role in stress-induced activation of the HPA axis and have been implicated in aggressive tendencies. Chronic stress can dysregulate the HPA axis, leading to alterations in cortisol levels and potentially contributing to aggressive behavior. The HPG axis, particularly the androgen hormone testosterone, is also closely linked to aggression. Animal and human studies have consistently shown a positive association between testosterone levels and aggression. The androgen receptors in the brain's neural circuitry play a critical role in modulating aggressive behavior. Interactions between the HPA and HPG axes further contribute to the regulation of aggression. Feedback mechanisms and crosstalk between these axes provide a complex system for the modulation of both stress and reproductive functions, which can impact aggressive behavior. Additionally,the influence of stress on reproductive functions, particularly the role of androgens in stress-induced aggression, adds further complexity to this relationship. The review also discusses the future directions and implications for clinical interventions. Understanding the neurobiological mechanisms underlying aggression requires integrating molecular, cellular, and circuit-level approaches. Translational perspectives, including animal models and human studies, can bridge the gap between basic research and clinical applications. Finally, therapeutic strategies for aggression-related disorders are explored, highlighting the importance of targeted interventions based on a comprehensive understanding of the interactions between the HPA and HPG axes. In conclusion, this review provides a comprehensive overview of the physiological and neurobiological mechanisms underlying aggression, with a specific focus on the interplay between the HPA and HPG axes. By elucidating the complex interactions between stress, hormones, and aggressive behavior, this research paves the way for future investigations and potential therapeutic interventions for aggression-related disorders.

Association of Maternal Air Pollution Exposure and Infant Lung Function Is Modified by Genetic Propensity to Oxidative Stress.

The association between air pollution and poor respiratory health outcomes is well established. Children are particularly at risk from air pollution, especially during the prenatal period as their organs and systems are still undergoing crucial development. This study investigated maternal exposure to air pollution during pregnancy and oxidative stress (OS), inflammation, and infant lung function at 4 weeks of age. Data from the Barwon Infant Study were available for 314 infants. The exposure to NO2 and PM2.5 were estimated. Infant lung function (4 weeks) was measured by multiple-breath washout. Glycoprotein acetyls (GlycA) (36 weeks prenatal), cord blood, and OS biomarkers were measured in maternal urine (28 weeks). A genetic pathway score for OS (gPFSox) was calculated. Linear regression was used and potential modification by the OS genotype was tested. There was no relationship between maternal exposure to air pollution and infant lung function, or with GlycA or OS during pregnancy. We found an association in children with a genetic propensity to OS between NO2 and a lower functional residual capacity (FRC) (β = -5.3 mls, 95% CI (-9.3, -1.3), p = 0.01) and lung clearance index (LCI) score (β = 0.46 turnovers, (95% CI 0.10, 0.82), p = 0.01). High prenatal exposure to ambient NO2 is associated with a lower FRC and a higher LCI score in infants with a genetic propensity to oxidative stress. There was no relationship between maternal exposure to air pollution with maternal and cord blood inflammation or OS biomarkers.

Stress field on intermediate length scales during triaxial compression

Defining a continuum stress field in a granular medium involves an approximation, as the underlying contact force network between particles is inhomogeneous and random. The continuum approximation introduces some baseline noise or variability in stress, which becomes more significant as the length scale of interest approaches the typical size of the grains. In this study, the authors evaluate how the stress variability resulting from the homogenisation of intergranular forces changes as the homogenisation scale is increased. This is done by obtaining the probability distribution function of stresses from a large number of repeated discrete-element method-based simulations of the triaxial compression of granular samples. The numerical experiments share sample dimensions, generation protocols and imposed stresses, but involve randomly generated sets of granular packings made of different numbers of particles. The results from this study are used to propose and develop a consistent general framework to rigorously describe mesoscale stress fields and hence fill the gap between existing micro- and macromechanical approaches. A backbone curve is obtained expressing the change in stress variability as the mesoscale is traversed. The results deduced from the backbone curve are in good agreement with those of independent numerical and physical experiments on granular soils.

Mitigating Effects of Tanacetum balsamita L. on Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD).

The metabolic syndrome and its associated co-morbidities have been recognized as predisposing risk factors for the development of metabolic-associated fatty liver disease (MAFLD). The present study reports on the beneficial effect of the Tanacetum balsamita methanol-aqueous extract (ETB) at 150 and 300 mg/kg bw on biochemical parameters related to oxidative stress, metabolic syndrome, and liver function in rat animal models with induced MAFLD. ETB was found to be non-toxic with LD50 > 3000 mg/kg and did not affect cell viability of hepatic HEP-G2 cells in a concentration up to 800 μg/mL. The pathology was established by a high-calorie diet and streptozotocin. Acarbose and atorvastatin were used as positive controls. At the higher dose, ETB reduced significantly (p < 0.05) the blood glucose levels by about 20%, decreased lipase activity by 52%, total cholesterol and triglycerides by 50% and 57%, respectively, and restored the amylase activity and leukocytes compared to the MAFLD group. ETB ameliorated oxidative stress biomarkers reduced glutathione and malondialdehyde in a dose-dependent manner. At 300 mg/kg, the beneficial effect of the extract on antioxidant enzymes was evidenced by the elevated catalase, glutathione peroxidase, and superoxide dismutase activity by 70%, 29%, and 44%, accordingly, compared to the MAFLD rats. ETB prevents the histopathological changes related to MAFLD. ETB, rich in 3,5-dicafeoylquinic, chlorogenic, and rosmarinic acids together with the isorhamnetin- and luteolin-glucoside provides a prominent amelioration of MAFLD.

A general solution for electromechanical analysis of electroelastic composite plates with arbitrary holes

Stroh formalism provides an elegant method of solution for two-dimensional anisotropic elasticity problems through the generalized eigen relation associated with the dual coordinate system that gives the material eigen values and eigen vectors, and also the fundamental elasticity matrix and its associated Barnett-Lothe tensors. The extended Stroh-like formalism of Hwu and Hsieh has expanded the scope of basic Stroh formalism by addressing the electro-mechanical coupling effects in electro elastic plates. This paper presents an inclusive solution that addresses the two-dimensional problems in infinite electro-elastic, anisotropic, and isotropic plates with an arbitrary hole under remote arbitrary coupled electro-mechanical loading. This is achieved by adopting the Stroh formalism and its subsequent versions to consider the anisotropic and electro-elastic plates, and further, by incorporating the arbitrary biaxial loading condition into the boundary conditions, and the generalized mapping function into the basic formulation to accommodate all types of in plane loading and a variety of hole shapes respectively. Various equations of the solution are derived explicitly for easy understanding and computer implementation. The stress function is derived explicitly to satisfy the condition of traction free hole with remote electro-mechanical loading under generalized plane stress-open circuit condition. The stresses and electric displacements around the hole boundary are obtained by taking the derivative of the stress function with respect to unit normal along the hole boundary. The solution presented can be degenerated to the anisotropic or isotropic case by choosing the corresponding material properties, or appropriate values of complex parameters respectively. This general solution has exactly reproduced the results of other solutions in the literature for piezoelectric plates given by different methods. New results of stresses and electric displacements are obtained for various arbitrary holes in [PZT5H/45/-45/PZT5H]s graphite/epoxy plate and PZT 4 plates. Results for holes in piezoelectric laminates and PZT 4 piezo layer are also presented by FEM.

The Role of Prolactin in Amniotic Membrane Regeneration: Therapeutic Potential for Premature Rupture of Membranes.

Premature rupture of membranes (PROM) is defined as rupture of fetal membranes before the onset of labor. Prolactin (PRL) is secreted by decidual membranes and accumulated significantly in the amniotic fluid during pregnancy. PRL could ameliorate inflammation and collagen degradation in fetal membranes. However, the role of PRL in amniotic membrane is not well characterized. We isolated human amniotic epithelial stem cells (hAESCs) from human fetal membranes to study the effect of PRL on proliferation, migration, and antioxidative stress. Amniotic pore culture technique (APCT) model was constructed to evaluate the tissue regeneration effect in vitro. The potential targets and pathways of PRL acting in amnion via integrated bioinformatic methods. PRL had a dose-dependent effect on hAESCs in vitro. PRL (500 ng/mL) significantly improved the viability of hAESCs and inhibited cell apoptosis, related to the upregulation of CCN2 expression and downregulation of Bax, Caspase 3, and Caspase 8. PRL accelerated migration process in hAESCs via downregulation of MMP2, MMP3, and MMP9. PRL attenuated the cellular damage and mitochondrial dysfunction induced by hydrogen peroxide in hAESCs. PRL accelerated the healing process in the APCT model significantly. The top 10 specific targets (IGF1R, SIRT1, MAP2K1, CASP8, MAPK14, MCL1, NFKB1, HIF1A, MTOR, and HSP90AA1) and signaling pathways (such as HIF signaling pathway) were selected using an integrated bioinformatics approach. PRL improves the viability and antioxidative stress function of hAESCs and the regeneration of ruptured amniotic membranes in vitro. Thus, PRL has great therapeutic potential for prevention and treatment of ruptured membranes.

The Impact of Weight Loss on Inflammation, Oxidative Stress, and Mitochondrial Function in Subjects with Obesity.

Inflammation, oxidative stress, and mitochondrial function are implicated in the development of obesity and its comorbidities. The purpose of this study was to assess the impact of weight loss through calorie restriction on the metabolic profile, inflammatory and oxidative stress parameters, and mitochondrial respiration in an obese population. A total of 109 subjects underwent two cycles of a very low-calorie diet alternated with a low-calorie diet (24 weeks). We analyzed biochemical and inflammatory parameters in serum, as well as oxidative stress markers, mRNA antioxidant gene expression, and mitochondrial respiration in peripheral blood mononuclear cells (PBMCs). After the intervention, there was an improvement in both insulin resistance and lipid profiles, including cholesterol subfractions. Weight loss produced a significant reduction in mitochondrial ROSs content and an increase in glutathione levels, coupled with an enhancement in the mRNA expression of antioxidant systems (SOD1, GSR, and CAT). In addition, a significant improvement in basal oxygen consumption, maximal respiration, and ATP production was observed. These findings demonstrate that moderate weight loss can improve insulin resistance, lipid profiles and subfractions, inflammatory and oxidative stress parameters, and mitochondrial respiration. Therefore, we can affirm that dietary intervention can simultaneously achieve significant weight loss and improve metabolic profile and mitochondrial function in obesity.

Mechanical Properties of Rock Salt from the Kłodawa Salt Dome-A Statistical Analysis of Geomechanical Data.

Rock salt is a potential medium for underground storage of energy resources and radioactive substances due to its physical and mechanical properties, distinguishing it from other rock media. Designing storage facilities that ensure stability, tightness, and safety requires understanding the geomechanical properties of rock salt. Despite numerous research efforts on the behaviour of rock salt mass, many cases still show unfavourable phenomena occurring within it. Therefore, the formulation of strength criteria in a three-dimensional stress state and the prediction of deformation processes significantly impact the functionality of storage in salt caverns. This article presents rock salt's mechanical properties from the Kłodawa salt dome and a statistical analysis of the determined geomechanical data. The analysis is divided into individual mining fields (Fields 1-6). The analysis of numerical parameter values obtained in uniaxial compression tests for rock salt from mining Fields 1-6 indicates an average variation in their strength and deformation properties. Upon comparing the results of Young's modulus (E) with uniaxial compressive strength (UCS), its value was observed with a decrease in uniaxial compressive strength (E = 4.19968·UCS2, R-square = -0.61). The tensile strength of rock salt from mining Fields 1-6 also exhibits moderate variability. An increasing trend in tensile strength was observed with increased bulk density (σt = 0.0027697·ρ - 4.5892, r = 0.60). However, the results of triaxial tests indicated that within the entire range of normal stresses, the process of increasing maximum shear stresses occurs linearly ((σ1 - σ3)/2 = ((σ1 + σ3)/2)·0.610676 + 2.28335, r = 0.92). A linear relationship was also obtained for failure stresses as a function of radial stresses (σ1 = σ3·2.51861 + 32.9488, r = 0.73). Based on the results, the most homogeneous rock salt was from Field 2 and Field 6, while the most variable rock salt was from Field 3.

SIRT4 Protects Müller Glial Cells Against Apoptosis by Mediating Mitochondrial Dynamics and Oxidative Stress.

SIRT4 is a member of the sirtuin family, which is related to mitochondrial function and possesses antioxidant and regulatory redox effects. Currently, the roles of SIRT4 in retinal Müller glial cells, oxidative stress, and mitochondrial function are still unclear. We confirmed, by immunofluorescence staining, that SIRT4 is located mainly in the mitochondria of retinal Müller glial cells. Using flow cytometry and Western blotting, we analyzed cell apoptosis, intracellular reactive oxygen species (ROS) levels, apoptotic and proapoptotic proteins, mitochondrial dynamics-related proteins, and mitochondrial morphology and number after the overexpression and downregulation of SIRT4 in rMC-1 cells. Neither the upregulation nor the downregulation of SIRT4 alone affected apoptosis. SIRT4 overexpression reduced intracellular ROS, reduced the BAX/BCL2 protein ratio, and increased the L-OPA/S-OPA1 ratio and the levels of the mitochondrial fusion protein MFN2 and the mitochondrial cleavage protein FIS1, increasing mitochondrial fusion. SIRT4 downregulation had the opposite effect. Mitochondria tend to divide after serum starvation for 24 h, and SIRT4 downregulation increases mitochondrial fragmentation and oxidative stress, leading to aggravated cell damage. The mitochondrial division inhibitor Mdivi-1 reduced oxidative stress levels and thus reduced cell damage caused by serum starvation. The overexpression of SIRT4 in rMC-1 cells reduced mitochondrial fragmentation caused by serum starvation, leading to mitochondrial fusion and reduced expression of cleaved caspase-3, thus alleviating the cellular damage caused by oxidative stress. Thus, we speculate that SIRT4 may protect retinal Müller glial cells against apoptosis by mediating mitochondrial dynamics and oxidative stress.

Nimbolide protects against diabetic cardiomyopathy by regulating endoplasmic reticulum stress and mitochondrial function via the Akt/mTOR pathway

Nimbolide has been demonstrated to possess protective properties against gestational diabetes mellitus and diabetic retinopathy. However, the role and molecular mechanism of nimbolide in diabetic cardiomyopathy (DCM) remain unknown. Diabetes was induced in rats via a single injection of streptozotocin (STZ) and then the diabetic rats were administered nimbolide (5 mg/kg and 20 mg/kg) or dimethyl sulfoxide daily for 12 weeks. H9c2 cardiomyocytes were exposed to high glucose (25 mM glucose) to mimic DCM in vitro. The protective effects of nimbolide against DCM were evaluated in vivo and in vitro. The potential molecular mechanism of nimbolide in DCM was further explored. We found that nimbolide dose-dependently decreased blood glucose and improved body weight of diabetic rats. Additionally, nimbolide dose-dependently improved cardiac function, alleviated myocardial injury/fibrosis, and inhibited endoplasmic reticulum (ER) stress and apoptosis in diabetic rats. Moreover, nimbolide dose-dependently improved mitochondrial function and activated the Akt/mTOR signaling. We consistently demonstrated the cardioprotective effects of nimbolide in an in vitro model of DCM. The involvement of ER stress and mitochondrial pathways were further confirmed by using inhibitors of ER stress and mitochondrial division. By applying a specific Akt inhibitor SC66, the cardioprotective effects of nimbolide were partially blocked. Our study indicated that nimbolide alleviated DCM by activating Akt/mTOR pathway. Nimbolide may be a novel therapeutic agent for DCM treatment.

A new approach to problems of thermoelasticity in stresses

It is known that the plane problems of the theory of elasticity and thermoelasticity are usually reduced to solving the biharmonic equation with respect to the Airy stress function. Solutions to spatial problems can also be defined using the Maxwell and Morera stress functions, etc. In this work, for solving a spatial thermoelastic problem, in the framework of the Beltrami-Michell equations, Poisson-type differential equations are found for each component of the stress tensor. In this case, the right-hand sides of these equations depend on temperature and elastic constants. The boundary conditions consist of the usual surface forces and “additional” boundary conditions derived from the equilibrium equations. The differential equations and boundary conditions of the plane problem of thermoelasticity in stresses are discussed in more detail. Grid equations for plane and spatial problems of thermoelasticity were compiled by the finite-difference method and solved by the iterative method. The problems of a thermoelastic rectangle and a parallelepiped located in a given temperature field are solved numerically. The validity of the formulated boundary value problems and the reliability of the results obtained are substantiated by comparing the numerical results with the solutions of the problems of a thermoelastic plate and a parallelepiped known in the literature.

Non-Destructive Hardness Indentation Measurement of Residual Stress on Large Aerospace Forged Components at the Engineering Site Based on Impact Hardness Tester.

Large forgings are crucial in aerospace applications; however, the residual stresses generated during their forming and heat treatment seriously affect their serviceability. Therefore, the non-destructive detection of residual stresses in large forgings is of far-reaching significance for ensuring the quality of forgings and realising precision machining. Although a variety of detection methods are available, there is still a lack of a programme that can comprehensively, accurately and non-destructively measure the residual stresses in large forgings. This study is dedicated to exploring the application of the bouncing impact indentation method in the non-destructive testing of residual stresses in large forgings. Through in-depth finite element simulations and orthogonal scheme analyses, we found that the elastic modulus, yield strength and work hardening indexes have significant effects on the impact indentation process. Further, we establish the dimensionless function of residual stress and indentation parameters, and successfully obtain the inversion algorithm of residual stress. The relative error of the calculated values of the indentation curves hm and hr in the simulation with reference values is not more than 3%, and the relative error of the corrected Pm inversion values for most virtual materials is not more than 5%. The folding elastic modulus and apparent elastic modulus obtained by inversion are controlled within 10%, which demonstrates a high value for engineering applications. In addition, we innovatively express the research results in the form of 3D stress diagrams, realising the digital expression of 3D residual stresses in large forgings based on feature point measurements and contour surface configurations, which provides intuitive and comprehensive data support for engineering practice.

Deletion of Dux ameliorates muscular dystrophy in mdx mice by attenuating oxidative stress via Nrf2.

DUX4 has been widely reported in facioscapulohumeral muscular dystrophy, but its role in Duchenne muscular dystrophy (DMD) is unclear. Dux is the mouse paralog of DUX4. In Dux-/- mdx mice, forelimb grip strength test and treadmill test were performed, and extensor digitorum longus (EDL) contraction properties were measured to assess skeletal muscle function. Pathological changes in mice were determined by serum CK and LDH levels and muscle Masson staining. Inflammatory factors, oxidative stress, and mitochondrial function indicators were detected using kits. Primary muscle satellite cells were isolated, and the antioxidant molecule Nrf2 was detected. MTT assay and Edu assay were used to evaluate proliferation and TUNEL assay for cell death. The results show that the deletion of Dux enhanced forelimb grip strength and EDL contractility, prolonged running time and distance in mdx mice. Deleting Dux also attenuated muscle fibrosis, inflammation, oxidative stress, and mitochondrial dysfunction in mdx mice. Furthermore, Dux deficiency promoted proliferation and survival of muscle satellite cells by increasing Nrf2 levels in mdx mice.

Hepatoprotective effects of resveratrol on α-amanitin-induced liver toxicity in rats

ObjectiveThe hepatoprotective effects of resveratrol against α-Amanitin (α-AMA)-induced liver toxicity were investigated in an experimental rat model, focusing on oxidative stress, inflammation, apoptosis, and liver function. MethodsThirty-two male Sprague-Dawley rats were divided into four groups (n = 8 per group): Control, resveratrol, α-AMA, and resveratrol+α-AMA. The resveratrol group received 20 mg/kg resveratrol orally for 7 days. The α-AMA group received 3 mg/kg α-AMA intraperitoneally on the 8th day. The resveratrol+α-AMA group received 20 mg/kg resveratrol orally (7 days) followed by 3 mg/kg α-AMA intraperitoneally on the 8th day. Liver tissues and blood samples were collected 48 h after α-amanitin administration for histopathological, immunohistochemical (NFkB, LC3B), and biochemical analyses (GSH, MDA, CAT, GPx, MPO, NOS, AST, ALT). Resultsα-AMA significantly increased AST and ALT levels, oxidative stress marker (MDA), and inflammatory marker (MPO), while reducing antioxidant levels (GSH, CAT, GPx) and NOS concentration (P < 0.001 for all parameters). Histopathological analysis showed severe liver damage with increased NFkB and LC3B expression. resveratrol treatment significantly reduced AST and ALT levels (P < 0.01 for both parameters), decreased MDA and MPO levels, and increased NOS concentration, GSH, CAT, and GPx levels (P < 0.05 for all parameters). Reduced NFkB and LC3B expression in the resveratrol+α-AMA group and showed histopathological improvements. ConclusionResveratrol demonstrated substantial hepatoprotective effects against α-AMA induced liver toxicity by reducing oxidative stress, inflammation, and apoptosis, and improving liver function. These findings suggest that resveratrol could be a potential therapeutic agent for treating liver damage caused by potent hepatotoxins like α-AMA.

A fatigue crack tip field model considering residual stress and plasticity-induced closure for welded structures

In order to more accurately understand and predict the fatigue crack growth behavior in welded structures, a fatigue crack tip field model considering residual stress and plasticity-induced closure (RSPC model) is presented in this paper. Building upon the existing CJP model, which adequately explains plasticity-induced crack closure, the RSPC model further considers the influence of tensile residual stress induced by welding. The model, through a detailed derivation and analysis of the residual stress function, establishes the theoretical stress and displacement fields at the crack tip of the butt-welded joint. Integrating these fields with the CJP model, the theoretical framework of the RSPC model is formulated. Subsequently, through fatigue crack growth experiments and digital image correlation analysis, a comparison and validation of the predictive performance of the CJP and RSPC models are conducted. It is observed that the latter aligns more closely with experimental results in calculating plastic zone area, with a maximum error of only 10%. In comparison to the CJP model, the average error decreases by 19.143%, indicating higher predictive accuracy. Furthermore, the study focuses on the contribution of tensile residual stress in butt welded joints to the growth of the plastic zone at the fatigue crack tip and the underlying reasons for its variations. Finally, the research investigates the constrained relationship between plastic zone size and fatigue crack growth rate. Corresponding relationship functions are fitted, providing more accurate guidance for crack control and material design.

Alleviative effect of scopolamine‑induced memory deficit via enhancing antioxidant and cholinergic function in rats by pinostrobin from Boesenbergia rotunda (L.).

Pinostrobin, a key bioactive compound found in the medicinal plant Boesenbergia rotunda (L.), has been noted for its beneficial biological properties including antioxidant, anti-inflammation, anti-cancer and anti-amnesia activities. In view of this, the present study purposed to evaluate the neuroprotective potential of pinostrobin in reversing scopolamine-induced cognitive impairment involving oxidative stress and cholinergic function in rats. A total of 30 male Wistar rats were randomly divided into five groups (n=6): Group 1 received vehicle as a control, group 2 received vehicle + scopolamine (3 mg/kg, i.p.), group 3 received pinostrobin (20 mg/kg, p.o.) + scopolamine, group 4 received pinostrobin (40 mg/kg, p.o.) + scopolamine and group 5 received donepezil (5 mg/kg, p.o.) + scopolamine. Treatments were administered orally to the rats for 14 days. During the final 7 days of treatment, a daily injection of scopolamine was administered. Scopolamine impaired learning and memory performance, as measured by the novel object recognition test and the Y-maze test. Additionally, oxidative stress marker levels, acetylcholinesterase (AChE) activity, choline acetyltransferase (ChAT) and glutamate receptor 1 (GluR1) expression were determined. Consequently, the findings demonstrated that the administration of pinostrobin (20 and 40 mg/kg) markedly improved cognitive function as indicated by an increase in recognition index and by spontaneous alternation behaviour. Pinostrobin also modulated the levels of oxidative stress by causing a decrease in malondialdehyde levels accompanied by increases in superoxide dismutase and glutathione activities. Similarly, pinostrobin markedly enhanced cholinergic function by decreasing AChE activity and promoting ChAT immunoreactivity in the hippocampus. Additionally, the reduction in GluR1 expression due to scopolamine was diminished by treatment with pinostrobin. The findings indicated that pinostrobin exhibited a significant restoration of scopolamine-induced memory impairment by regulating oxidative stress and cholinergic system function. Thus, pinostrobin could serve as a potential therapeutic agent for the management of neurodegenerative diseases such as Alzheimer's disease.

Gubra Amylin-NASH Diet Induced Nonalcoholic Fatty Liver Disease Associated with Histological Damage, Oxidative Stress, Immune Disorders, Gut Microbiota, and Its Metabolic Dysbiosis in Colon.

The overall changes of colon under nonalcoholic fatty liver disease (NAFLD) remain to be further elucidated. This study establishes a mouse model of NAFLD through a long-term Gubra Amylin-nonalcoholic steatohepatitis (NASH) diet (GAN diet). The results show that GAN diet significantly induces weight gain, liver steatosis, colonic oxidative stress, and lipid accumulation in blood, liver, and adipose tissue in mice. GAN feeding reduces the diversity of the gut microbiota, alters the composition and abundance of the gut microbiota, and leads to an increase in microbial metabolites such as long-chain fatty acids (LCFAs) and secondary bile acids (BAs), as well as a decrease in short-chain fatty acids (SCFAs). The RNA-seq and immunofluorescence results reveal that the GAN diet alters the expression of proteins and their coding genes involved in oxidative stress, immune response, and barrier function in colon tissue, such as lipocalin-2 (Lcn2, p<0.05), heme oxygenase-1 (HO-1/Hmox1, p<0.05), interferon-gamma (IFN-γ), and claudin-3/7. In addition, correlation analysis indicates a strong correlation between the changes in gut microbiota and lipid biomarkers. Additionally, the expression of immune related genes in colon tissue is related to the LCFAs produced by microbial metabolism. GAN-induced NAFLD is related to microbiota and its metabolic imbalance, oxidative stress, immune disorders, and impaired barrier function in colon.

Impaired mitochondrial quality control in fibromyalgia: Mechanisms involved in skeletal muscle alteration

Fibromyalgia (FMS) is a persistent syndrome marked by widespread musculoskeletal pain and behavioural symptoms. Given the hypothesis linking FMS aetiology to mitochondrial dysfunction and oxidative stress, we examined the biochemical correlation among these factors by studying specific proteins associated with mitochondrial homeostasis in muscle. Additionally, this study investigated the role of Boswellia serrata gum resin extract (BS), known for its various functions, including the potent induction of antioxidant enzymes, in determining protective or reparative mechanisms in the muscle cells. Sprague–Dawley rats were injected with reserpine to induce FMS.These animals exhibited moderate changes in hind limb skeletal muscles, experiencing mobility difficulties. Additionally, there were noteworthy morphological and ultrastructural alterations, along with the expression of myogenin, mitochondrial enzymes and oxidative stress markers in the gastrocnemius muscle. Interestingly, BS demonstrated a reduction in spontaneous motor activity difficulties. Moreover, BS showed a positive impact on musculoskeletal morphostructural aspects, as well as a decrease in oxidative stress and mitochondrial alterations. In particular, BS restored the mRNA expression of citrate synthase and cytochrome-c oxidase subunit II and the activity of electron transfer chain complexes. BS also influenced mitochondrial biogenesis, upregulating PGC-1α expression and the related transcription factors (Nrf1, Tfam, Nrf2, FOXO3a, SIRT3, GCLC, NQO1, SOD2 and GPx4), oxidative stress (lipid peroxidation, GSH levels and GSH-Px activity) and mitochondrial dynamics and function (Mnf2 expression and CoQ10 levels). Overall, this study underlined the key role of the mitochondrial alteration in FMS and that BS had a very high antioxidant effect in these organelles and also in the cells.

Alpha-Synuclein Interaction with UBL3 Is Upregulated by Microsomal Glutathione S-Transferase 3, Leading to Increased Extracellular Transport of the Alpha-Synuclein under Oxidative Stress.

Aberrant aggregation of misfolded alpha-synuclein (α-syn), a major pathological hallmark of related neurodegenerative diseases such as Parkinson's disease (PD), can translocate between cells. Ubiquitin-like 3 (UBL3) is a membrane-anchored ubiquitin-fold protein and post-translational modifier. UBL3 promotes protein sorting into small extracellular vesicles (sEVs) and thereby mediates intercellular communication. Our recent studies have shown that α-syn interacts with UBL3 and that this interaction is downregulated after silencing microsomal glutathione S-transferase 3 (MGST3). However, how MGST3 regulates the interaction of α-syn and UBL3 remains unclear. In the present study, we further explored this by overexpressing MGST3. In the split Gaussia luciferase complementation assay, we found that the interaction between α-syn and UBL3 was upregulated by MGST3. While Western blot and RT-qPCR analyses showed that silencing or overexpression of MGST3 did not significantly alter the expression of α-syn and UBL3, the immunocytochemical staining analysis indicated that MGST3 increased the co-localization of α-syn and UBL3. We suggested roles for the anti-oxidative stress function of MGST3 and found that the effect of MGST3 overexpression on the interaction between α-syn with UBL3 was significantly rescued under excess oxidative stress and promoted intracellular α-syn to extracellular transport. In conclusion, our results demonstrate that MGST3 upregulates the interaction between α-syn with UBL3 and promotes the interaction to translocate intracellular α-syn to the extracellular. Overall, our findings provide new insights and ideas for promoting the modulation of UBL3 as a therapeutic agent for the treatment of synucleinopathy-associated neurodegenerative diseases.

Protective Role of Ellagic Acid Against Ethanol-Induced Neurodevelopmental Disorders in Newborn Male Rats: Insights into Maintenance of Mitochondrial Function and Inhibition of Oxidative Stress.

Ellagic acid (EA) exerts, neuroprotective, mitoprotective, anti-oxidative and anti-inflammatory effects. We evaluated protective effect of EA on ethanol-induced fetal alcohol spectrum disorders (FASD). A total of 35 newborn male rats were used, divided into five groups, including; control (normal saline), ethanol (5.25 g/kg per day), ethanol (5.25 g/kg per day) + EA (10 mg/kg), ethanol (5.25 g/kg per day) + EA (20 mg/kg) and ethanol (5.25 g/kg per day) + EA (40 mg/kg). Thirty-six days after birth behavioral tests (Morris water maze and Elevated Plus Maze), tumor necrosis factor-α (TNF-α) levels, oxidative markers (malondialdehyde, glutathione and superoxide dismutase), mitochondrial examination such as succinate dehydrogenases (SDH) activity, mitochondrial swelling, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) formation were analyzed. The results revealed that ethanol exposure adversely affected cognitive and mitochondrial functions and as well as induced oxidative stress and inflammation in brain tissue. However, EA (20 and 40 mg/kg) administration effectively prevented the toxic effects of ethanol in FASD model. These findings demonstrate that ethanol application significantly impairs the brain development via mitochondrial dysfunction and induction of oxidative stress. These data indicate that EA might be a useful compound for prevention of alcohol-induced FASD.