Search Results (28,135)

The high-glucose conditions caused by diabetes mellitus (DM) exert several effects on cells, including inflammation. miR-146a, a kind of miRNA, is involved in inflammation and may be regulated mutually with reactive oxygen species (ROS), which are produced under high-glucose conditions. In the present study, we used human periodontal ligament cells (hPDLCs) to determine the effects of the high-glucose conditions of miR-146a and their involvement in the regulation of oxidative stress and inflammatory cytokines using Western blotting, PCR, ELISA and other methods. When hPDLCs were subjected to high glucose (24 mM), cell proliferation was not affected; inflammatory cytokine expression, ROS induction, interleukin-1 receptor-associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6) expression increased, but miR-146a expression decreased. Inhibition of ROS induction with the antioxidant N-acetyl-L-cysteine restored miR-146a expression and decreased inflammatory cytokine expression compared to those under high-glucose conditions. In addition, overexpression of miR-146a significantly suppressed the expression of the inflammatory cytokines IRAK1 and TRAF6, regardless of the glucose condition. Our findings suggest that oxidative stress and miR-146a expression are mutually regulated in hPDLCs under high-glucose conditions. Full article

Reynoutria ciliinervis (Nakai) Moldenke (R. ciliinervis) root, a traditional Chinese medicine, was found to exhibit remarkable pharmacological properties through a series of comprehensive investigations. Our study commenced with a qualitative phytochemical analysis that identified 12 bioactive compounds within the plant. Subsequently, utilizing ultraviolet-visible spectrophotometry, the methanol extract emerged as the optimal solvent extract, which was abundant in diverse classes of compounds such as carbohydrates, phenolics, steroids, alkaloids, phenolic acids, and tannins. In vitro antioxidant assays underscored the exceptional free radical scavenging, metal ion chelation, hydrogen peroxide scavenging, singlet oxygen quenching, and β-carotene bleaching capabilities of the methanol extract, significantly outperforming other solvent extracts. Further ultra high-performance liquid chromatography–electrospray ionization–quadrupole time of flight–mass spectrometry analysis revealed the presence of 45 compounds, predominantly anthraquinones and phenolics, in the methanol extract. The extract demonstrated robust stability under various conditions, including high temperatures, varying pH levels, and simulated gastrointestinal digestion as well as efficacy in inhibiting the oxidation in edible oils. Acute toxicity tests in mice confirmed the safety of the methanol extract and provided a valuable dosage reference for future studies. Importantly, high-dose methanol extract exhibited a significant pre-protective effect against D-galactosamine-induced liver injury in rats, as evidenced by reduced alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, malondialdehyde levels, and elevated catalase and albumin levels. These findings suggest a potential role for the methanol extract of R. ciliinervis root in treating oxidative stress-related disorders, highlighting the plant’s immense medicinal potential. Our research offers a thorough evaluation of the bioactive components, antioxidant properties, stability, and liver-protecting effects of the methanol extract, setting the stage for deeper investigation and potential clinical applications. Full article

Objectives: To determine the effect of short-term metformin administration on follicular fluid (FF) total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI) and nuclear factor kappa B (NF-kB) in women with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). Methods: Fifty-eight patients aged 23–34 who were planned to have intracytoplasmic sperm injection due to clomiphene citrate-resistant PCOS were included in the study. Participants were divided into two groups according to whether they used metformin or not. While 30 of 58 PCOS patients were using short-term metformin in combination with controlled ovarian stimulation, 28 PCOS patients were not using metformin. Metformin was started in the mid-luteal period and continued until the day before oocyte retrieval at 850 mg twice daily. To determine FF-NF-kB, TAS, TOS and OSI values, a dominant follicle ≥17–18 mm in diameter was selected for aspiration. Results: The number of mature follicles and fertilization rates of the metformin group were significantly higher than those not taking metformin. FF-TOS and OSI of the metformin group were significantly lower than those of the group not receiving metformin. Patients receiving metformin had higher FF-TAS than the group not receiving metformin. FF-NF-kB levels of the metformin group were significantly lower than the group not receiving metformin. Insulin resistance, FF-NF-kB and FF-TOS were negatively correlated with the number of mature oocytes. FF-TAS was positively correlated with the number of oocytes. Conclusions: Short-term metformin treatment in clomiphene-resistant PCOS improves the number of mature follicles and fertilization rates by regulating the intra-follicle redox balance. Full article

5,6-dihydroxyflavone (5,6-DHF), a flavonoid that possesses potential anti-inflammatory and antioxidant activities owing to its special catechol motif on the A ring. However, its function and mechanism of action against inflammation and cellular oxidative stress have not been elucidated. In the current study, 5,6-DHF was observed inhibiting lipopolysaccharide (LPS)-induced nitric oxide (NO) and cytoplasmic reactive oxygen species (ROS) production with the IC₅₀ of 11.55 ± 0.64 μM and 0.8310 ± 0.633 μM in murine macrophages, respectively. Meanwhile, 5,6-DHF suppressed the overexpression of pro-inflammatory mediators such as proteins and cytokines and eradicated the accumulation of mitochondrial ROS (mtROS). The blockage of the activation of cell surface toll-like receptor 4 (TLR4), impediment of the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 from the mitogen-activated protein kinases (MAPK) pathway, Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) from the JAK-STAT pathway, and p65 from nuclear factor-κB (NF-κB) pathways were involved in the process of 5,6-DHF suppressing inflammation. Furthermore, 5,6-DHF acted as a cellular ROS scavenger and heme-oxygenase 1 (HO-1) inducer in relieving cellular oxidative stress. Importantly, 5,6-DHF exerted more potent anti-inflammatory activity than its close structural relatives, such as baicalein and chrysin. Overall, our findings pave the road for further research on 5,6-DHF in animal models. Full article

Background: obesity is a worldwide problem that seriously endangers human health. Canola oil (Col) has been reported to regulate hepatic steatosis by influencing oxidative stress and lipid metabolism in Kunming mice. However, whether Col exhibits an anti-obesity effect by altering the gut microbiota remains unknown. Methods: in this study, we observed that a high-fat diet increased lipogenesis and gut microbiota disorder in C57BL/6J male mice, while the administration of Col suppressed lipogenesis and improved gut microbiota disorder. Results: the results show that Col markedly reduced the final body weight and subcutaneous adipose tissue of C57BL/6J male mice fed a high-fat diet (HFD) after 6 weeks of administration. However, although Col did not effectively increase the serum concentration of HDL, we found that treatment with Col notably inhibited the low-density lipoprotein (LDL), total cholesterol (TC), and triglycerides (TGs) in HFD mice. Furthermore, Col ameliorated obesity in the liver compared to mice that were only fed a high-fat diet. We also found that Col significantly inhibited the relative expression of sterol regulatory element binding protein (SREBP1/2), peroxisome proliferator-activated receptor γ (PPARγ), and insulin-induced genes (Insig1/2) that proved to be closely associated with lipogenesis in HFD mice. In addition, the concentration of acetic acid was significantly increased in Col-treatment HFD mice. Further, we noted that Col contributed to the reprogramming of the intestinal microbiota. The relative abundances of Akkermansia, Dubosiella, and Alistipes were enhanced under treatment with Col in HFD mice. The results also imply that Col markedly elevated the phosphorylation level of the AMP-activated protein kinase (AMPK) pathway in HFD mice. Conclusions: the results of our study show that Col ameliorates obesity and suppresses lipogenesis in HFD mice. The underlying mechanisms are possibly associated with the reprogramming of the gut microbiota, in particular, the acetic acid-mediated increased expression of Alistipes via the AMPK signaling pathway. Full article

Heavy ion radiation, prevalent in outer space and relevant for radiotherapy, is densely ionizing and poses a risk to intestinal stem cells (ISCs), which are vital for maintaining intestinal homeostasis. Earlier studies have shown that heavy-ion radiation can cause chronic oxidative stress, persistent DNA damage, cellular senescence, and the development of a senescence-associated secretory phenotype (SASP) in mouse intestinal mucosa. However, the specific impact on different cell types, particularly Lgr5⁺ intestinal stem cells (ISCs), which are crucial for maintaining cellular homeostasis, GI function, and tumor initiation under genomic stress, remains understudied. Using an ISCs-relevant mouse model (Lgr5⁺ mice) and its GI tumor surrogate (Lgr5⁺Apc^1638N/+ mice), we investigated ISCs-specific molecular alterations after high-LET radiation exposure. Tissue sections were assessed for senescence and SASP signaling at 2, 5 and 12 months post-exposure. Lgr5+ cells exhibited significantly greater oxidative stress following ²⁸Si irradiation compared to γ-ray or controls. Both Lgr5⁺ cells and Paneth cells showed signs of senescence and developed a senescence-associated secretory phenotype (SASP) after ²⁸Si exposure. Moreover, gene expression of pro-inflammatory and pro-growth SASP factors remained persistently elevated for up to a year post-²⁸Si irradiation. Additionally, p38 MAPK and NF-κB signaling pathways, which are critical for stress responses and inflammation, were also upregulated after ²⁸Si radiation. Transcripts involved in nutrient absorption and barrier function were also altered following irradiation. In Lgr5⁺Apc^1638N/+ mice, tumor incidence was significantly higher in those exposed to ²⁸Si radiation compared to the spontaneous tumorigenesis observed in control mice. Our results indicate that high-LET ²⁸Si exposure induces persistent DNA damage, oxidative stress, senescence, and SASP in Lgr5⁺ ISCs, potentially predisposing astronauts to altered nutrient absorption, barrier function, and GI carcinogenesis during and after a long-duration outer space mission. Full article

Background/Objectives: This review aims to provide a detailed understanding of the current evidence on Alpinia officinarum Hance (A. officinarum) and its potential therapeutic role in central nervous system (CNS) disorders. CNS disorders encompass a wide range of disorders affecting the brain and spinal cord, leading to various neurological, cognitive and psychiatric impairments. In recent years, natural products have emerged as potential neuroprotective agents for the treatment of CNS disorders due to their outstanding bioactivity and favourable safety profile. One such plant is A. officinarum, also known as lesser galangal, a perennial herb from the Zingiberaceae family. Its phytochemical compounds such as flavonoids and phenols have been documented to have a powerful antioxidants effect, capable of scavenging free radicals and preventing oxidative damage. Methods: In this review, we critically evaluate the in vitro and in vivo studies and examine the mechanisms by which A. officinarum exerts its neuroprotective effect. Results: Several studies have confirmed that A. officinarum exerts its neuroprotective effects by reducing oxidative stress and cell apoptosis, promoting neurite outgrowth, and modulating neurotransmitter levels and signalling pathways. Conclusions: Although previous studies have shown promising results in various models of neurological disorders, the underlying mechanisms of A. officinarum in Alzheimer’s (AD) and Parkinson’s disease (PD) are still poorly understood. Further studies on brain tissue and cognitive and motor functions in animal models of AD and PD are needed to validate the results observed in in vitro studies. In addition, further clinical studies are needed to confirm the safety and efficacy of A. officinarum in CNS disorders. Full article

The high-risk Human Papillomavirus (HR-HPV) is the causal agent of different human cancers such as cervical, vulvar, and oropharynx cancer. This is because persistent HR-HPV infection alters several cellular processes involved in cell proliferation, apoptosis, immune evasion, genomic instability, and cellular transformation. The above is mainly due to the expression of early expression proteins of HR-HPV, which interact and alter these processes. HR-HPV proteins have even been shown to regulate redox state and mitochondrial metabolism, which has been suggested as a risk factor for cancer development. Redox state refers to a balance between reactive oxygen species (ROS) and antioxidants. Although ROS regulates cell signaling, high levels of ROS generate oxidative stress (OS). OS promotes damage to DNA, proteins, carbohydrates, and lipids, which causes mutation accumulation and genome instability associated with cancer development. Thus, OS has been associated with the establishment and development of different types of cancer and has recently been proposed as a cofactor in HR-HPV-associated cancers. However, OS also induces cell death, which can be used as a target for different molecules, such as phytochemicals. Furthermore, phytochemicals target HPV oncoproteins E6 and E7, causing their degradation. Because phytochemicals could induce OS and target HPV oncoproteins, we hypothesize that these compounds induce cell death in HPV-associated cancers. Since the redox state is crucial in developing, establishing, and clearing HR-HPV-associated cancer, this review focuses on evidence for using phytochemicals as therapeutic agents that target HPV proteins and the redox state to induce the elimination of HPV-related cancers. Full article

The transformation protocol based on the dual selection approach (fluorescent protein and herbicide resistance) has been applied here to produce transgenic plants of two cereal species, emmer wheat and bread wheat, with the goal of activating the synthesis of the stress hormone jasmonates by overexpressing ALLENE OXIDE SYNTHASE from Arabidopsis thaliana (AtAOS) and bread wheat (TaAOS) and OXOPHYTODIENOATE REDUCTASE 3 from A. thaliana (AtOPR3) under the strong constitutive promoter (ZmUbi1), either individually or both genes simultaneously. The delivery of the expression cassette encoding AOS was found to affect morphogenesis in both wheat species negatively. The effect of transgene expression on the accumulation of individual jasmonates in hexaploid and tetraploid wheat was observed. Among the introduced genes, overexpression of TaAOS was the most successful in increasing stress-inducible phytohormone levels in transgenic plants, resulting in higher accumulations of JA and JA-Ile in emmer wheat and 12-OPDA in bread wheat. In general, overexpression of AOS, alone or together with AtOPR3, negatively affected leaf lamina length and grain numbers per spike in both wheat species. Double (AtAOS + AtOPR3) transgenic wheat plants were characterized by significantly reduced plant height and seed numbers, especially in emmer wheat, where several primary plants failed to produce seeds. Full article

Background: Glucose 6 phosphate dehydrogenase (G6PD) is a rate-limiting enzyme of the pentose phosphate pathway. The loss of G6PD activity in red blood cells increases the risk of acute haemolytic anaemia under oxidative stress induced by infections, some medications, or fava beans. More than 200 single missense mutations are known in the G6PD gene. A 41-year-old woman with a family history of favism coming from the Basilicata region (Italy) was evaluated at our hospital for G6PD abnormalities. Methods: DNA was extracted from a peripheral blood sample and genotyped for the most common G6PD pathogenic variants (PVs). Positive results obtained by Restriction Fragment Length Polymorphism (RFLP), as per practice in our laboratory, were then reconfirmed in Sanger sequencing. Results: RFLP analysis highlighted a variant compatible with the G6PD Cassano variant. Confirmatory testing by Sanger unexpectedly identified a novel variant: c.1357G>A, p.(Val453Met) (NM_001360016.2); the same variant was found in the patient’s mother. In silico models predicted a deleterious effect of this variant at the protein level. The novel G6PD variant was named “G6PD Potenza” on the basis of the patient’s regional origin. Conclusions: This case describes a novel G6PD variant. It also highlights how the Sanger sequencing technique still represents an indispensable confirmatory standard method for variants that could be misinterpreted by only using a “first-level” approach, such as the RFLP. We stress that the evaluation of clinical manifestations in G6PD-deficient patients is of primary importance for the classification of each new G6PD mutation, in agreement with the new WHO guidelines. Full article

Toxicity mechanisms of per- and polyfluoroalkyl substances (PFASs), a chemical class present in diverse ecosystems, as well as many of their precursors, have been increasingly characterized in aquatic species. Perfluorooctanesulfonamide (PFOSA, C₈H₂F₁₇NO₂S) is a common precursor of perfluorooctane sulfonic acid (PFOS), a long-chain PFAS. Here, we assessed sub-lethal endpoints related to development, oxidative stress, transcript levels, and distance moved in zebrafish embryos and larvae following continuous exposure to PFOSA beginning at 6 h post-fertilization (hpf). PFOSA decreased survival in fish treated with 1 µg/L PFOSA; however, the effect was modest relative to the controls (difference of 10%). Exposure up to 10 µg/L PFOSA did not affect hatch rate, nor did it induce ROS in 7-day-old larvae fish. The activity of larval fish treated with 100 µg/L PFOSA was reduced relative to the solvent control. Transcripts related to oxidative stress response and apoptosis were measured and BCL2-associated X, apoptosis regulator (bax), cytochrome c, somatic (cycs), catalase (cat), superoxide dismutase 2 (sod2) were induced with high concentrations of PFOSA. Genes related to neurotoxicity were also measured and transcript levels of acetylcholinesterase (ache), elav-like RNA binding protein 3 (elavl3), growth-associated protein 43 (gap43), synapsin II (syn2a), and tubulin 3 (tubb3) were all increased in larval fish with higher PFOSA exposure. These data improve our understanding of the potential sub-lethal toxicity of PFOSA in fish species. Full article

Algae, both micro- and macroalgae, are recognized for their rich repository of bioactive compounds with potential therapeutic applications. These marine organisms produce a variety of secondary metabolites that exhibit significant anti-inflammatory, antioxidant, and antimicrobial properties, offering promising avenues for the development of new drugs and nutraceuticals. Algae-derived compounds, including polyphenols, carotenoids, lipids, and polysaccharides, have demonstrated efficacy in modulating key inflammatory pathways, reducing oxidative stress, and inhibiting microbial growth. At the molecular level, these compounds influence macrophage activity, suppress the production of pro-inflammatory cytokines, and regulate apoptotic processes. Studies have shown that algae extracts can inhibit inflammatory signaling pathways such as NF-κB and MAPK, reduce oxidative damage by activating Nrf2, and offer an alternative to traditional antibiotics by combatting bacterial infections. Furthermore, algae’s therapeutic potential extends to addressing diseases such as cardiovascular disorders, neurodegenerative conditions, and cancer, with ongoing research exploring their efficacy in preclinical animal models. The pig model, due to its physiological similarities to humans, is highlighted as particularly suitable for validating the bioactivities of algal compounds in vivo. This review underscores the need for further investigation into the specific mechanisms of action and clinical applications of algae-derived biomolecules. Full article

Salt stress could be a significant factor limiting the growth and development of vegetables. In this study, Fulvic Acid (FA) (0.05%, 0.1%, 0.15%, 0.2%, and 0.25%) was applied under nitrate stress (150 mM), with normal Hoagland nutrient solution as a control to investigate the influence of foliar spray FA on spinach growth, photosynthesis, and oxidative stress under nitrate stress. The results showed that nitrate stress significantly inhibited spinach growth, while ROS (reactive oxygen species) accumulation caused photosystem damage, which reduced photosynthetic capacity. Different concentrations of FA alleviated the damage caused by nitrate stress in spinach to varying degrees in a concentration-dependent manner. The F3 treatment (0.15% FA + 150 mM NO₃⁻) exhibited the most significant mitigating effect. FA application promoted the accumulation of biomass in spinach under nitrate stress and increased chlorophyll content, the net photosynthetic rate, the maximum photochemical quantum yield of PSII (Photosystem II) (Fv/Fm), the quantum efficiency of PSII photochemistry [Y(II)], the electron transport rate, and the overall functional activity index of the electron transport chain between the PSII and PSI systems (PItotal); moreover, FA decreased PSII excitation pressure (1 − qP), quantum yields of regulated energy dissipation of PSII [Y(NPQ)], and the relative variable initial slope of fluorescence. FA application increased superoxide dismutase, peroxidase, and catalase activities and decreased malondialdehyde, H₂O₂, and O₂⁻ levels in spinach under nitrate stress. FA can enhance plant resistance to nitrate by accelerating the utilization of light energy in spinach to mitigate excess light energy and ROS-induced photosystem damage and increase photosynthetic efficiency. Full article

Pomegranate extract has potential benefits for women’s reproductive health, including fertility enhancement, menstrual cycle regulation, pregnancy support, and polycystic ovary syndrome (PCOS) treatment. It possesses antioxidant properties, reducing oxidative stress and improving fertility. Pomegranate extract may help regulate hormonal imbalances and promote regular menstrual cycles. The extract’s rich nutrient profile supports placental development and fetal growth and may reduce the risk of preterm birth. Additionally, pomegranate extract shows promise in improving insulin sensitivity and reducing inflammation and oxidative damage in PCOS. Some studies suggest its potential anticancer properties, particularly against breast cancer. However, further research, including human clinical trials, is necessary to establish its effectiveness and safety. The current evidence is limited and primarily based on in vitro studies, animal studies, and clinical trials. This review provides a comprehensive summary of the benefits of pomegranate extract for women’s reproductive health and breast cancer, serving as a reference for future research. Full article

Zinc oxide nanoparticles (NPs) are used in a wide range of consumer products and in biomedical applications, resulting in an increased production of these materials with potential for exposure, thus causing human health concerns. Although there are many reports on the size-related toxicity of ZnO NPs, the toxicity of different nanoforms of this chemical, toxicity mechanisms, and potency determinants need clarification to support health risk characterization. A set of well-characterized ZnO nanoforms (e.g., uncoated ca. 30, 45, and 53 nm; coated with silicon oil, stearic acid, and (3-aminopropyl) triethoxysilane) were screened for in vitro cytotoxicity in two cell types, human lung epithelial cells (A549), and mouse monocyte/macrophage (J774) cells. ZnO (bulk) and ZnCl₂ served as reference particles. Cytotoxicity was examined 24 h post-exposure by measuring CTB (viability), ATP (energy metabolism), and %LDH released (membrane integrity). Cellular oxidative stress (GSH-GSSG) and secreted proteins (targeted multiplex assay) were analyzed. Zinc oxide nanoform type-, dose-, and cell type-specific cytotoxic responses were seen, along with cellular oxidative stress. Cell-secreted protein profiles suggested ZnO NP exposure-related perturbations in signaling pathways relevant to inflammation/cell injury and corresponding biological processes, namely reactive oxygen species generation and apoptosis/necrosis, for some nanoforms, consistent with cellular oxidative stress and ATP status. The size, surface area, agglomeration state and metal contents of these ZnO nanoforms appeared to be physicochemical determinants of particle potencies. These findings warrant further research on high-content “OMICs” to validate and resolve toxicity pathways related to exposure to nanoforms to advance health risk-assessment efforts and to inform on safer materials. Full article