Search Results (27,702)

Rice bran, which is abundant in dietary fiber and phytochemicals, provides multiple health benefits. Nonetheless, its effects on neuroinflammation and gut microbiota in postmenopausal conditions are still not well understood. This study investigated the effects of rice bran and/or tea seed oil supplementation in d-galactose-injected ovariectomized (OVX) old mice fed a fructose drink. The combination of d-galactose injection, ovariectomy, and fructose drink administration creates a comprehensive model that simulates aging in females under multiple metabolic stressors, including oxidative stress, estrogen deficiency, and high-sugar diets, and allows the study of their combined impact on metabolic disorders and related diseases. Eight-week-old and 6–8-month-old female C57BL/6 mice were used. The mice were divided into six groups: a sham + young mice, a sham + old mice, an OVX + soybean oil, an OVX + soybean oil with rice bran, an OVX + tea seed oil (TO), and an OVX + TO with rice bran diet group. The OVX groups were subcutaneously injected with d-galactose (100 mg/kg/day) and received a 15% (v/v) fructose drink. The rice bran and tea seed oil supplementation formed 10% of the diet (w/w). The results showed that the rice bran with TO diet increased the number of short-chain fatty acid (SCFA)-producing Clostridia and reduced the number of endotoxin-producing Tannerellaceae, which mitigated imbalances in the gut–liver–brain axis. Rice bran supplementation reduced the relative weight of the liver, levels of hepatic triglycerides and total cholesterol; aspartate transaminase and alanine aminotransferase activity; brain levels of proinflammatory cytokines, including interleukin-1β and tumor necrosis factor-α; and plasma 8-hydroxy-2-deoxyguanosine. This study concludes that rice bran inhibits hepatic fat accumulation, which mitigates peripheral metaflammation and oxidative damage and reduces neuroinflammation in the brain. Full article

Cells constantly face the challenge of managing oxidants. In aerobic organisms, oxygen (O₂) is used for energy production, generating reactive oxygen species (ROS) as byproducts of enzymatic reactions. To protect against oxidative damage, cells possess an intricate system of redox scavengers and antioxidant enzymes, collectively forming the antioxidant defense system. This system maintains the redox equilibrium and enables the generation of localized oxidative signals that regulate essential cellular functions. One key component of this defense is the thioredoxin (Trx) system, which includes Trx, thioredoxin reductase (TrxR), and NADPH. The Trx system reverses oxidation of macromolecules and indirectly neutralizes ROS via peroxiredoxin (Prx). This dual function protects cells from damage accumulation and supports physiological cell signaling. However, the Trx system also shields tumors from oxidative damage, aiding their survival. Due to elevated ROS levels from their metabolism, tumors often rely on the Trx system. In addition, the Trx system regulates critical pathways such as proliferation and neoangiogenesis, which tumors exploit to enhance growth and optimize nutrient and oxygen supply. Consequently, the Trx system is a potential target for cancer therapy. The challenge lies in selectively targeting malignant cells without disrupting the redox equilibrium in healthy cells. The aim of this review article is threefold: first, to elucidate the function of the Trx system; second, to discuss the Trx system as a potential target for cancer therapies; and third, to present the possibilities for inhibiting key components of the Trx system, along with an overview of the latest clinical studies on these inhibitors. Full article

The complex structure of monoclonal antibodies (mAbs) expressed in Chinese hamster ovary (CHO) cells may result in the accumulation of unfolded proteins, triggering endoplasmic reticulum (ER) stress and an unfolded protein response (UPR). If the protein folding ability cannot maintain ER homeostasis, the cell will shut down protein translation and ultimately induce apoptosis. We co-overexpressed HsQSOX1b and survivin proteins in the antibody-producing cell line CHO-PAb to obtain a new cell line, CHO-PAb-QS. Compared with CHO-PAb cells, the survival time of CHO-PAb-QS cells in batch culture was extended by 2 days, and the antibody accumulation and productivity were increased by 52% and 45%, respectively. The proportion of (HC-LC)₂ was approximately doubled in the CHO-PAb-QS cells, which adapted to the accelerated disulfide bond folding capacity by upregulating the UPR’s strength and increasing the ER content. The results of the apoptosis assays indicated that the CHO-PAb-QS cell line exhibited more excellent resistance to apoptosis induced by ER stress. Finally, CHO-PAb-QS cells exhibited mild oxidative stress but did not significantly alter the redox status. This study demonstrated that strategies based on HsQSOX1b and survivin co-overexpression could facilitate protein disulfide bond folding and anti-apoptosis ability, enhancing antibody production efficiency in CHO cell lines. Full article

Olive oil coproducts and their phenolic extracts have shown beneficial effects when added to the diets of food-producing animals, whereas data on their effects on pets are scarce. The aim of this study was to evaluate the effects of dietary supplementation with olive flour (MOP^®) on oxidative blood biomarkers in dogs. Thirty dogs were recruited and divided into two groups. Both groups were fed the same kibble feed twice daily. The treatment group (T) also received canned wet feed supplemented with 11.5 mg/kg of body weight of organic olive flour per day, whereas the control group (C) received the same wet feed without any supplementation. The findings showed that oil-free olive pulp flour supplementation led to a significant decrease in d-ROMs (p < 0.044) in the blood of the T group (from 101.26 to 86.67 U CARR), whereas no significant changes were observed in the C group. An increasing OXY trend was found in the blood of the T group. Polyphenols in olive flour at a dose of 11.5 mg/kg of body weight contributed to lowering the oxidative stress threshold in dogs, reducing the levels of d-ROMs in dogs and leading to increasing trends in the amount of blood antioxidants. The use of olive pulp flour in dog diets has proven to be beneficial for their health and could also reduce the waste associated with olive oil production. Full article

Out-of-season breeding is an effective method for addressing seasonal shortages of fry in aquaculture species such as largemouth bass (LMB) for year-round production. Off-season breeding of LMB can be achieved by subjecting breeding LMB to prolonged low-temperature conditions; however, this can alter reproductive rhythms, affecting the quality of their sperm and leading to a decrease in reproductive efficiency. Therefore, it is crucial to investigate issues such as the damage to the testes and the related mechanisms caused by low-temperature stress during out-of-season breeding. In this experiment, we assessed the changes in the testes during this time in LMB by comparing reproductive rhythms, testicular histomorphology, ultrastructure, antioxidant capacity and apoptosis. We synthesized measurements of LMB from three identically treated cement ponds and fish exposed to water temperatures of 13–16 °C to assess the changes in the testes. The results showed that (1) out-of-season reproduction delayed sperm production and promoted sperm redevelopment in LMB, various hormone levels have changed over time (e.g., LH, FSH, and T). (2) The head plasma membrane of LMB spermatozoa was separated, and the middle mitochondria were swollen. (3) The expression levels of antioxidant enzymes (cat, sod, and gpx) were upregulated, and oxidative stress occurred in LMB. (4) The expression levels of apoptosis genes (e.g., bax, bcl2, and caspase3) were upregulated, and apoptosis occurred in LMB due to off-season breeding. Moreover, important genes of the mitochondrial apoptosis pathway (bid, CYT-C) were upregulated, indicating that spermatozoan apoptosis in LMB was probably achieved through the mitochondrial apoptosis pathway. These results suggest the delays, damage, and regeneration of LMB testes. Our findings provide new insights into the molecular mechanisms that trigger changes in sperm quality during out-of-season breeding in fish. Full article

Caffeine is one of the most commonly used drugs in intensive care to stimulate the respiratory control mechanisms of very preterm infants. Respiratory instability, due to the degree of immaturity at birth, results in apnea of prematurity (AOP), hyperoxic, hypoxic, and intermittent hypoxic episodes. Oxidative stress cannot be avoided as a direct reaction and leads to neurological developmental deficits and even a higher prevalence of respiratory diseases in the further development of premature infants. Due to the proven antioxidant effect of caffeine in early use, largely protective effects on clinical outcomes can be observed. This is also impressively observed in experimental studies of caffeine application in oxidative stress-adapted rodent models of damage to the developing brain and lungs. However, caffeine shows undesirable effects outside these oxygen toxicity injury models. This review shows the effects of caffeine in hyperoxic, hypoxic/hypoxic-ischemic, and intermittent hypoxic rodent injury models, but also the negative effects on the rodent organism when caffeine is administered without exogenous oxidative stress. The narrative analysis of caffeine benefits in cerebral and pulmonary preterm infant models supports protective caffeine use but should be given critical consideration when considering caffeine treatment beyond the recommended corrected gestational age. Full article

Mercury (Hg) pro-oxidant role on biological systems and its biogeochemical cycle represent a serious threat due to its persistence in marine environment. As the mitochondrial genome is exposed to reactive oxygen species (ROS), the aim of the present study is the validation of the variation in the number of mitochondrial DNA copies (mtDNAcn) as biomarker of oxidative stress in aquatic environment. During summer 2021, three selected fish species (Mullus barbatus, Diplodus annularis and Pagellus erythrinus) were collected in Augusta Bay, one of the most Mediterranean contaminated areas remarkable by past Hg inputs, and in a control area, both in the south-east of Sicily. The relative mtDNAcn was evaluated by qPCR on specimens of each species from both sites, characterized respectively by higher and lower Hg bioaccumulation. M. barbatus and P. erythrinus collected in Augusta showed a dramatic mtDNAcn reduction compared to their control groups while D. annularis showed an incredible mtDNAcn rising suggesting a higher resilience of this species. These results align with the mitochondrial dynamics of fission and fusion triggered by environmental toxicants. In conclusion, we suggest the implementation of the mtDNAcn variation as a valid tool for the early warning stress-related impacts in aquatic system. Full article

Cardiolipin (CL), a critical phospholipid situated within the mitochondrial membrane, plays a significant role in modulating intramitochondrial processes, especially in the context of certain cardiac pathologies; however, the exact effects of alterations in cardiolipin on septic cardiomyopathy (SCM) are still debated and the underlying mechanisms remain incompletely understood. This study highlights a notable increase in the expressions of ALCAT1 and PLSCR3 during the advanced stage of lipopolysaccharide (LPS)-induced SCM. This up-regulation potential contribution to mitochondrial dysfunction and cellular apoptosis—as indicated by the augmented oxidative stress and cytochrome c (Cytc) release—coupled with reduced mitophagy, decreased levels of the antiapoptotic protein B-cell lymphoma-2 (Bcl-2) and lowered cell viability. Additionally, the timing of LPS-induced apoptosis coincides with the decline in both autophagy and mitophagy at the late stages, implying that these processes may serve as protective factors against LPS-induced SCM in HL-1 cells. Together, these findings reveal the mechanism of LPS-induced CL changes in the center of SCM, with a particular emphasis on the importance of pathological remodeling and translocation of CL to mitochondrial function and apoptosis. Additionally, it highlights the protective effect of mitophagy in the early stage of SCM. This study complements previous research on the mechanism of CL changes in mediating SCM. These findings enhance our understanding of the role of CL in cardiac pathology and provide a new direction for future research. Full article

Pomegranate is a notable source of nutrients, containing a considerable proportion of organic acids, polysaccharides, vitamins, fatty acids, and polyphenols such as flavonoids, phenolic acids, and tannins. It is also rich in nutritionally important minerals and chemical elements such as K, P, Na, Ca, Mg, and N. The presence of several bioactive compounds and metabolites in pomegranate has led to its incorporation into the functional food category, where it is used for its numerous therapeutic properties. Pomegranate’s bioactive compounds have shown antioxidant, anti-inflammatory, and anticancer effects. Aging is a process characterized by the chronic accumulation of damages, progressively compromising cells, tissues, and organs over time. Inflammaging is a chronic, subclinical, low-grade inflammation that occurs during the aging process and is linked to many age-related diseases. This review aims to summarize and discuss the evidence of the benefits of pomegranate extract and its compounds to slow the aging processes by intervening in the mechanisms underlying inflammaging. These studies mainly concern neurodegenerative and skin diseases, while studies in other fields of application need to be more practical. Furthermore, no human studies have demonstrated the anti-inflammaging effects of pomegranate. In the future, supplementation with pomegranate extracts, polyphenols, or urolithins could represent a valuable low-risk complementary therapy for patients with difficult-to-manage diseases, as well as a valid therapeutic alternative for the topical or systemic treatment of skin pathologies. Full article

Neuroinflammation is a critical aspect of various neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. This study investigates the anti-neuroinflammatory properties of oleocanthal and its oxidation product, oleocanthalic acid, using the BV-2 cell line activated with lipopolysaccharide. Our findings revealed that oleocanthal significantly inhibited the production of pro-inflammatory cytokines and reduced the expression of inflammatory genes, counteracted oxidative stress induced by lipopolysaccharide, and increased cell phagocytic activity. Conversely, oleocanthalic acid was not able to counteract lipopolysaccharide-induced activation. The docking analysis revealed a plausible interaction of oleocanthal, with both CD14 and MD-2 leading to a potential interference with TLR4 signaling. Since our data show that oleocanthal only partially reduces the lipopolysaccharide-induced activation of NF-kB, its action as a TLR4 antagonist alone cannot explain its remarkable effect against neuroinflammation. Proteomic analysis revealed that oleocanthal counteracts the LPS modulation of 31 proteins, including significant targets such as gelsolin, clathrin, ACOD1, and four different isoforms of 14-3-3 protein, indicating new potential molecular targets of the compound. In conclusion, oleocanthal, but not oleocanthalic acid, mitigates neuroinflammation through multiple mechanisms, highlighting a pleiotropic action that is particularly important in the context of neurodegeneration. Full article

Background: Obesity is characterized by increased oxidative stress, which, in a vicious circle, promotes chronic low-grade inflammation. Melatonin, a well-documented antioxidant, might be useful as a supplement to enhance the cardiometabolic benefits of any body weight reduction program (BWRP). Objectives/Methods: The present study aimed to evaluate the post-exercise oxidative stress and inflammation in a group of subjects with obesity treated with melatonin (2 mg/die) or placebo, undergoing a 2-week BWRP, with the administration of a single bout of acute exercise at the start and the end of the protocol (G1–G15). Results: Eighteen adults with obesity were enrolled and distributed to the two arms of the study: the melatonin group (F/M: 7/2; age: 27.8 ± 5.6 years; body mass index [BMI]: 43.0 ± 4.9 kg/m²) and the placebo group (F/M: 6/3; age: 28.8 ± 5.0 years; BMI: 42.8 ± 4.0 kg/m²). BWRP induced a decrease in BMI and waist circumference (WC) in both groups; plasma glucose, blood glycated hemoglobin (HbA_1c), and neutrophil to lymphocyte ratio (NLR) were reduced only in the placebo group. Importantly, plasma biological antioxidant potential (BAP) increased throughout BWRP. Paradoxically, melatonin enhanced post-exercise production of plasma derivatives of reactive oxygen metabolites (d-ROMs) and erythrocytic glutathionyl-Hb (HbSSG) (at G1 and G15). Finally, differently from the placebo group, melatonin-treated subjects did not exhibit the BWRP-induced decrease in plasma levels of interleukin-6 (IL-6), before and after exercise, at the end of two weeks (G15). Conclusions: Melatonin is presumably an antioxidant with “conditional” prooxidant actions. The use of melatonin as a supplement in subjects with obesity might be deleterious due to the abolishment of BWRP-induced cardiometabolic benefits. Full article

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are chronic syndromes of unknown etiology, accompanied by numerous symptoms affecting neurological and physical conditions. Despite frequent revisions of the diagnostic criteria, clinical practice guidelines are often outdated, leading to underdiagnosis and ineffective treatment. Our aim was to identify microRNA (miRNA) biomarkers implicated in pathological mechanisms underlying these diseases. A comprehensive literature review using publicly accessible databases was conducted. Interesting miRNAs were extracted from relevant publications on ME/CFS and/or FM, and were then linked to pathophysiological processes possibly manifesting these chronic diseases. Dysregulated miRNAs in ME/CFS and FM may serve as promising biomarkers for these diseases. Key identified miRNAs, such as miR-29c, miR-99b, miR-128, miR-374b, and miR-766, were frequently mentioned for their roles in immune response, mitochondrial dysfunction, oxidative stress, and central sensitization, while miR-23a, miR-103, miR-152, and miR-320 were implicated in multiple crucial pathological processes for FM and/or ME/CFS. In summary, both ME/CFS and FM seem to share many dysregulated biological or molecular processes, which may contribute to their commonly shared symptoms. This miRNA-based approach offers new angles for discovering molecular markers urgently needed for early diagnosis or therapeutics to tackle the pathology of these medically unexplained chronic diseases. Full article

Hepatic fibrosis with various origins can be estimated non-invasively by using certain biomarkers and imaging-based measurements. The aim of our study was to examine redox homeostasis biomarkers and liver stiffness measurements for the assessment of significant liver fibrosis in different etiologies of chronic liver diseases. A cohort study consisting of 88 chronic liver disease patients of both sexes (age 49.1 ± 14.7 years) was performed. Cytokine profiles as well as redox homeostasis characteristics were determined. Liver fibrosis stages were assessed with shear wave elastography. The plasma levels of four cytokines showed no significant alteration between the four fibrotic stages; however, higher values were measured in the F2–4 stages. Free sulfhydryl group concentration, the marker of redox homeostasis, was lower in significant fibrosis (F0–F1: 0.36 ± 0.06 vs. F2–4: 0.29 ± 0.08 mmol/L, p < 0.05). Higher chemiluminescence values, as free radical–antioxidant parameters, were detected in advanced fibrosis stages in erythrocytes (F0–F1: 36.00 ± 37.13 vs. F2–4: 51.47 ± 44.34 RLU%). These data suggest that oxidative stress markers can predict significant fibrosis, with the aim of reducing the number of protocol liver biopsies in patients unlikely to have significant disease; however, their role in distinguishing between the certain fibrosis groups needs further studies. Full article

Background: Alcohol abuse is one of the most common causes of mortality worldwide. This study aimed to investigate the efficacy of a treatment in reducing circulating ethanol and oxidative stress biomarkers. Methods: Twenty wine-drinking subjects were investigated in a randomized controlled, single-blind trial (ClinicalTrials.gov. Identifier: NCT06548503; Ethical Committee of the University of Padova (HEC-DSB/12-2023) to evaluate the effect of the intake of a product containing silymarin, pyrroloquinoline quinone sodium salt, and myricetin (referred to as Si.Pi.Mi. for this project) on blood alcohol, ethyl glucuronide (EtG: marker for alcohol consumption) and markers of oxidative stress levels (Reactive Oxygen Species—ROS, Total Antioxidant Capacity—TAC, CoQ10, thiols redox status, 8-isoprostane, NO metabolites, neopterin, and uric acid). The effects of the treatment versus placebo were evaluated acutely and after 1 week of supplementation in blood and/or saliva and urine samples. Results: Si.Pi.Mi intake reduced circulating ethanol after 120 min (−33%). Changes in oxidative stress biomarkers, particularly a TAC (range +9–12%) increase and an 8-isoprostane (marker of lipidic peroxidation) decrease (range −22–27%), were observed too. Conclusion: After the administration of Si.Pi.Mi, the data seemed to suggest a better alcohol metabolism and oxidative balance in response to wine intake. Further verification is requested. Full article

Frailty and cardiovascular diseases are increasingly prevalent in aging populations, sharing common pathological mechanisms, such as oxidative stress. The evidence shows that these factors predispose frail individuals to cardiovascular diseases but also increase the risk of thrombosis. Considering this background, this review aims to explore advances regarding the relationship between oxidative stress, platelet alterations, and cardiovascular diseases in frailty, examining the role of reactive oxygen species overproduction in platelet activation and thrombosis. The current evidence shows a bidirectional relationship between frailty and cardiovascular diseases, emphasizing how frailty not only predisposes individuals to cardiovascular diseases but also accelerates disease progression through oxidative damage and increased platelet function. Thus, oxidative stress is the central axis in the increase in platelet activation and secretion and the inadequate response to acetylsalicylic acid observed in frail people by mitochondrial mechanisms. Also, key biomarkers of oxidative stress, such as isoprostanes and derivate reactive oxygen metabolites, can be optimal predictors of cardiovascular risk and potential targets for therapeutic intervention. The potential of antioxidant therapies in mitigating oxidative stress and improving cardiovascular clinical outcomes such as platelet function is promising in frailty, although further research is necessary to establish the efficacy of these therapies. Understanding these mechanisms could prove essential in improving the health and quality of life of an aging population faced with the dual burden of frailty and cardiovascular diseases. Full article