Search Results (2,828)

Phospholipids (PLs) are a group of biomolecules found in the milk fat globule membranes (MFGMs). Recently, MFGM phospholipids have attracted increasing amounts of attention due to their unique composition, stability, and potential health benefits, including protective effects against Alzheimer’s disease, hypercholesterolemia, and certain types of cancer. Although buffalo milk is the second most commonly produced milk and has high nutritional value, few studies have focused on the properties of buffalo MFGM. This study investigates the PLs composition of buffalo milk and related dairy by-products (whey and buttermilk). Milk and whey were collected from two dairy farms (A—small and B—big) to produce mozzarella buffalo cheese (high-pasteurization milk for GDO production and low for local); while buttermilk was obtained from a butter-making farm. Phospholipids were purified by a solid-phase extraction method and then identified by high-performance liquid chromatography with an evaporative light-scattering detector (HPLC/ELSD). Five classes of phospholipids [phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), and sphingomyelin (SM)] were identified. The thermal process of milk did not significantly affect the PLs milk. However, local whey showed a higher concentration of total PLs than GDO, which was mainly represented by PE followed by PC content. Farm A exhibited higher PL content than B, particularly with a greater concentration of SM. Buttermilk showed the lowest PLs content. These findings offer valuable insights for the dairy industry and related applications, contributing to the valorization of buffalo dairy products. Full article

In vitro cartilage explant culture has been used to assess nutraceuticals on cartilage responses to inflammatory stimuli. However, applying extracts of nutraceuticals directly to cartilage explants does not account for effects of digestion and hepatic biotransformation, or selective exclusion of product metabolites from joint fluid by the synovial membrane. The current study produced a simulated biological extract of a common nutraceutical (glucosamine; G_sim) by exposing it to a simulated upper gastrointestinal tract digestion, hepatic biotransformation by liver microsomes, and purification to a molecular weight cut-off of 50 kDa. This extract was then used to condition cartilage explants cultured for 120 h in the presence or absence of an inflammatory stimulus (lipopolysaccharide). Media samples were analyzed for prostaglandin E₂ (PGE₂), glycosaminoglycan (GAG), and nitric oxide (NO). Tissue was digested and analyzed for GAG content and stained for viability. Conditioning of explants with G_sim significantly reduced media GAG in stimulated and unstimulated explants and reduced nitric oxide production in unstimulated explants. These data provide evidence for the value of glucosamine in protecting cartilage from deterioration following an inflammatory challenge, and the model improves applicability of these in vitro data to the in vivo setting. Full article

Morus alba L. (MA) is a member of the Moraceae family, known as “white mulberry”. Due to the high levels of bioactive compounds, mulberry plants can be considered a good source of nutrients and antioxidant compounds. Our study aims to analyze the effect of MA extract leaves on erythrocytes, focusing on its action on metabolism and membrane integrity. The choice of erythrocytes as a study model is based on their metabolic simplicity and their easy availability. Cell viability, following exposure of the cells to the extract, was evaluated by hemolysis, methemoglobin, caspase 3 activity and flow cytofluorimetric analysis; in addition, the effect of the pretreatment with the MA was detected after incubation of erythrocytes with different stressors. The impact on cell metabolism was evaluated by measuring anion flux kinetics, ATP levels and phosphatase activity. The results obtained show a peculiar (double) effect of the extract, which, on the one hand, probably by exploiting its component with antioxidant properties, protects the cell membrane by accumulating on the bilayer. On the other hand, the alteration of anion exchange could lead to the triggering of apoptosis and consequent cell death. The hypotheses, although excluded by our data, all point toward a beneficial and protective action of the extract on the health and vitality of RBCs. Full article

An imbalance between the generation of reactive oxygen species (ROS) and antioxidant defenses is known as oxidative stress, and it is implicated in a number of diseases. The superoxide radical O^2– is produced by numerous biochemically relevant redox processes and is thought to play role in diseases and pathological processes, such as aging, cancer, membrane or DNA damage, etc.; SOD, or superoxide dismutase, is essential for reducing oxidative stress. As a result, the elimination of ROS by SOD may be a useful disease prevention tactic. There have been reports of protective effects against neurodegeneration, apoptosis, carcinogenesis, and radiation. Exogenous SODs’ low bioavailability has drawn criticism. However, this restriction might be removed, and interest in SOD’s medicinal qualities increased with advancements in its formulation. This review discusses the findings of human and animal studies that support the benefits of SOD enzyme regulation in reducing oxidative stress in various ways. Additionally, this review summarizes contemporary understandings of the biology of Cu/Zn superoxide dismutase 1 (SOD1) from SOD1 genetics and its therapeutic potential. Full article

It has long been accepted that breathing gases that are physiologically inert include helium (He), neon (Ne), nitrogen (N₂), argon (Ar), krypton (Kr), xenon (Xe), and hydrogen (H₂). The term “inert gas” has been used to describe them due to their unusually high chemical stability. However, as investigations have advanced, many have shown that inert gas can have specific biological impacts when exposed to high pressure or atmospheric pressure. Additionally, different inert gases have different effects on intracellular signal transduction, ion channels, and cell membrane receptors, which are linked to their anesthetic and cell protection effects in normal or pathological processes. Through a selective analysis of the representative literature, this study offers a concise overview of the state of research on the biological impacts of inert gas and their molecular mechanisms. Full article

High-performance waterproof and breathable nanofiber membranes (WBNMs) are in great demand for various advanced applications. However, the fabrication of such membranes often relies on fluorinated materials or involves complex preparation processes, limiting their practical use. In this study, we present an innovative approach by utilizing silicon-containing polyurethane (SiPU) as a single-component, fluorine-free raw material to prepare high-performance WBNMs via a simple one-step electrospinning process. The electrospinning technique enables the formation of SiPU nanofibrous membranes with a small maximum pore size (d_max) and high porosity, while the intrinsic hydrophobicity of SiPU imparts excellent water-repellent characteristics to the membranes. As a result, the single-component SiPU WBNM exhibits superior waterproofness and breathability, with a hydrostatic pressure of 52 kPa and a water vapor transmission rate (WVTR) of 5798 g m⁻² d⁻¹. Moreover, the optimized SiPU-14 WBNM demonstrates outstanding mechanical properties, including a tensile strength of 6.15 MPa and an elongation at break of 98.80%. These findings indicate that the single-component SiPU-14 WBNMs not only achieve excellent waterproof and breathable performance but also possess robust mechanical strength, thereby enhancing the comfort and expanding the potential applications of protective textiles, such as outdoor apparel and car seats. Full article

Fungicides are compounds with potentially toxic effects on the human body, but the molecular mechanisms of their action have not yet been explained. The effect of cyprodinil on cell viability, apoptosis level, cell membrane function, cell morphology and expression of antioxidant enzyme genes in the A-375 and DLD-1 cell lines was examined. The cell lines were selected because they can be an excellent in vitro model of neoplastic changes occurring in the skin and large intestine after exposure to a fungicide. The fungicide selected for the study is commonly used in Poland to protect crops against fungi. Our results showed that the tested compound increased cell viability and proliferation, probably activated by mechanisms related to oxidative stress. Cyprodinil caused an increase in glutathione level (in A-375 by about 37% and in DLD-1 by about 28%) and oxidative stress enzymes activity, but not in apoptosis level. Its membrane interactions and its penetration into cells was concentration dependent. It is worth emphasizing that the novelty of our work lies in the use of non-traditional toxicological methods based on molecular analyses using human cell lines. This allowed us to demonstrate not only the toxicity of a single substance but also its behavior within cellular structures. Our findings suggest that cyprodinil may have tumor-promoting properties in skin and colorectal cancer cells. Full article

The administration of isolated mitochondria is a promising strategy for protecting cells from oxidative damage. This study aimed to identify mitochondrial characteristics that contribute to stronger protective effects. We compared two types of mitochondria isolated from C6 cells with similar ATP-producing capacity but differing in outer membrane integrity. To evaluate their stability in extracellular conditions, we examined their behavior in serum. Both types underwent mitochondrial permeability transition to a similar extent; however, under intracellular-like conditions after serum incubation, mitochondria with intact membranes retained more polarized mitochondria. Notably, mitochondria with intact outer membranes were internalized more efficiently than those with damaged membranes. In H9c2 cells, both types of mitochondria similarly increased intracellular ATP levels 1 h after administration under all tested conditions. When co-administered with H₂O₂, both suppressed oxidative damage to a comparable degree, as indicated by similar H₂O₂-scavenging activity in solution, comparable intracellular ROS levels, and equivalent preservation of electron transport chain activity. However, at higher H₂O₂ concentrations, cells treated with mitochondria possessing intact outer membranes exhibited greater survival 24 h after co-administration. Furthermore, when mitochondria were added after H₂O₂-induced damage and their removal, intact mitochondria conferred superior cell survival compared to damaged ones. These findings suggest that while both mitochondrial types exert comparable antioxidant effects, outer membrane integrity prior to administration plays a critical role in enhancing cell survival under conditions of oxidative stress. Full article

Lower respiratory tract infections remain a leading cause of morbidity and mortality among Intensive Care Unit patients, with severe cases often progressing to acute respiratory distress syndrome (ARDS). This life-threatening syndrome results from alveolar–capillary membrane injury, causing refractory hypoxemia and respiratory failure. Early detection and management are critical to treat the underlying cause, provide protective lung ventilation, and, eventually, improve patient outcomes. The 2012 Berlin definition standardized ARDS diagnosis but excluded patients on non-invasive ventilation (NIV) or high-flow nasal cannula (HFNC) modalities, which are increasingly used, especially after the COVID-19 pandemic. By excluding these patients, diagnostic delays can occur, risking the progression of lung injury despite ongoing support. Indeed, sustained, vigorous respiratory efforts under non-invasive modalities carry significant potential for patient self-inflicted lung injury (P-SILI), underscoring the need to broaden diagnostic criteria to encompass these increasingly common therapies. Recent proposals expand ARDS criteria to include NIV and HFNCs, lung ultrasound, and the SpO₂/FiO₂ ratio adaptations designed to improve diagnosis in resource-limited settings lacking arterial blood gases or advanced imaging. However, broader criteria risk overdiagnosis and create challenges in distinguishing ARDS from other causes of acute hypoxemic failure. Furthermore, inter-observer variability in imaging interpretation and inconsistencies in oxygenation assessment, particularly when relying on non-invasive measurements, may compromise diagnostic reliability. To overcome these limitations, a more nuanced diagnostic framework is needed—one that incorporates individualized therapeutic strategies, emphasizes lung-protective ventilation, and integrates advanced physiological or biomarker-based indicators like IL-6, IL-8, and IFN-γ, which are associated with worse outcomes. Such an approach has the potential to improve patient stratification, enable more targeted interventions, and ultimately support the design and conduct of more effective interventional studies. Full article

Vibrio parahaemolyticus is a major foodborne pathogen worldwide, responsible for seafood-associated poisoning. Among its toxin genes, tdh2 is the most critical. To investigate the role of tdh2 in V. parahaemolyticus under gastrointestinal conditions, we constructed tdh2 deletion and complementation strains and compared their survival under acid (pH 3 and 4) and bile stress (2%). The results showed that tdh2 expression was significantly upregulated under cold (4 °C) and bile stress (0.9%). Survival assays and PI staining revealed that the tdh2 mutant strain (VP: △tdh2) was more sensitive to acid and bile stress than the wild-type (WT), and this sensitivity was rescued by tdh2 complementation. These findings suggest that tdh2 plays a protective role in enhancing V. parahaemolyticus tolerance to acid and bile stress. In the VP: △tdh2 strain, seven genes were significantly upregulated and six were downregulated as a result of tdh2 deletion. These genes included VPA1332 (vtrA), VPA1348 (vtrB), VP2467 (ompU), VP0301 and VP1995 (ABC transporters), VP0527 (nhaR), and VP2553 (rpoS), among others. Additionally, LC-MS/MS analysis identified 12 differential metabolites between the WT and VP: △tdh2 strains, including phosphatidylserine (PS) (17:2 (9Z,12Z) /0:0 and 20:1 (11Z) /0:0), phosphatidylglycerol (PG) (17:0/0:0), flavin mononucleotide (FMN), and various nucleotides. The protective mechanism of tdh2 may involve preserving cell membrane permeability through regulation of ompU and ABC transporters and enhancing electron transfer efficiency via regulation of nhaR. The resulting reduction in ATP, DNA, and RNA synthesis—along with changes in membrane permeability and electron transfer due to decreased FMN—likely contributed to the reduced survival of the VP: △tdh2 strain. Meanwhile, the cells actively synthesized phospholipids to repair membrane damage, leading to increased levels of PS and PG. This study provides important insights into strategies for preventing and controlling food poisoning caused by tdh⁺ V. parahaemolyticus. Full article

Objectives: To investigate the efficacy and underlying mechanisms of IBCar’s biological activity in breast cancer models, both in cell culture and in mice, and to compare its effects on cancer versus normal cells. Methods: The cytotoxicity of IBCar was evaluated using the MTS assay to assess metabolic activity and the clonogenic assay to determine reproductive integrity. The impact of IBCar on microtubule integrity, mitochondrial function, and multiple signaling pathways was analyzed using Western blotting, microarray analysis, and live cell imaging. The therapeutic effectiveness of orally administered IBCar was assessed in a transgenic mouse model of Luminal B breast cancer and in mice implanted with subcutaneous triple-negative breast cancer xenografts. Results: IBCar demonstrated potent cytotoxicity across a diverse panel of breast cancer cell lines, including those with mutant or wild-type TP53, and cell lines with short and long doubling times. Comparative analysis revealed distinct responses between normal and cancer cells, including differences in IBCar’s effects on the mitochondrial membrane potential, endoplasmic reticulum stress and activation of cell death pathways. In breast cancer cells, IBCar was cytotoxic at nanomolar concentrations, caused irreversible microtubule depolymerization leading to sustained mitochondrial dysfunction, endoplasmic reticulum stress, and induced apoptosis. In normal cells, protective mechanisms included reversible microtubule depolymerization and activation of pro-survival signaling via the caspase-8 and riptosome pathways. The therapeutic potential of IBCar was confirmed in mouse models of Luminal B and triple negative BC, where it exhibited strong antitumor activity without detectable toxicity. Conclusions: These findings collectively support IBCar as a promising, effective, and safe therapeutic candidate for breast cancer treatment. Full article

Liquid storage is an important tool used to prolong fresh semen shelf-life while protecting spermatozoa from damage, conserving their overall functionality, and ensuring better fertility than frozen semen from sheep. The increased production of reactive oxygen species (ROS) during sperm storage leads to a decline in sperm quality, particularly with regard to sperm nuclear DNA damage and mitochondrial membrane potential (MMP). This study evaluated the effect of storing Sarda ram semen at 15 °C for 7 h on its redox status, motility, morphology, acrosome integrity, ATP content, mitochondrial potential membrane, and in vivo fertility after artificial insemination. Two different extenders were compared: a lab-made skimmed milk (SM)-based extender and a commercial extender (OviXcell^®, IMV-Technologies, France). Lower ROS levels in the SM (p < 0.001) indicated that its oxidative status was better maintained compared to the commercial extender (CE). Antioxidant defenses (total antioxidant capacity, TEAC; superoxide dismutase, SOD; total thiols) were higher in the SM (p < 0.01) than in the CE. SM also had higher MMP (p < 0.05), acrosome integrity (p < 0.05), ATP content (p < 0.01), and in vivo fertilizing capacity (p < 0.05) compared to the CE, which indicated higher semen quality. In conclusion, the SM extender, while maintaining a better oxidative/antioxidant balance, ensured higher semen quality after 7 h of storage at 15 °C in vitro compared to the CE. Full article

Background: Rehmannia glutinosa, a traditional Chinese herb, is commonly used to treat vascular-related disorders. Sepsis-associated vascular endothelial dysfunction is closely associated with mitochondrial damage. This study investigated the protective effects of secondary metabolites from R. glutinosa against LPS-induced mitochondrial dysfunction in endothelial cells, providing potential therapeutic insights into sepsis-related vascular complications. Methods: Phytochemical profiling of fresh R. glutinosa roots was conducted, and the structures of new secondary metabolites (1 and 2) were elucidated through comprehensive spectroscopic analysis and ECD calculations. UPLC-Q-TOF-MS/MS characterized phenylethanoid glycosides. Mitochondrial function was assessed by measuring the membrane potential, ROS levels, and TOM20/DRP1 expression in LPS-injured HUVECs. Results: Two novel eremophilane-type sesquiterpenes, remophilanetriols J (1) and K (2), along with five known phenylethanoid glycosides (3–7), were isolated from the fresh roots of R. glutinosa. UPLC-Q-TOF-MS/MS analysis revealed unique fragmentation pathways for phenylethanoid glycosides (3–7). In LPS-injured HUVECs, all compounds collectively restored the mitochondrial membrane potential, attenuated ROS accumulation, and modulated TOM20/DRP1 expression. In particular, remophilanetriol K (2) exhibited potent protective effects at a low concentration (1.5625 μM). Conclusions: This study identifies R. glutinosa metabolites as potential therapeutics for sepsis-associated vascular dysfunction by preserving mitochondrial homeostasis. This study provides a mechanistic basis for the traditional use of R. glutinosa and offers valuable insights into the development of novel therapeutics targeting mitochondrial dysfunction in sepsis. Full article

Background/Objectives: Curcumin is a promising therapy for glioblastoma but is limited by poor water solubility, rapid metabolism, and low blood–brain barrier penetration. This study aimed to evaluate curcumin and six curcumin derivatives with improved activity against a glioblastoma cell line and favorable absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. Methods: Twenty-one curcumin derivatives were assessed and subjected to in vitro MTT cytotoxicity assays in SF268 glioblastoma and Vero cells. On the basis of the cytotoxicity results, six derivatives with the most favorable characteristics were selected for additional mechanistic studies, which included microtubule depolymerization, mitochondrial membrane potential (ΔΨm), and BAX activation assays. ADMET properties were determined in silico. Results: Compounds 2–4, 6, and 11 demonstrated better activity (IC₅₀: 0.59–3.97 µg/mL and SI: 3–20) than curcumin (IC₅₀: 6.3 µg/mL; SI: 2.5). Lead derivatives destabilized microtubules, induced ΔΨm collapse, and activated BAX. In silico ADMET prediction analysis revealed that compounds 4 and 6 were the most promising for oral administration from a biopharmaceutical and pharmacokinetic point of view. Conclusions: Strategic modifications were made to one or both hydroxyl groups of the aromatic rings of curcumin to increase its physicochemical stability and activity against glioblastoma cell line SF268. Compound 4, bearing fully protected aromatic domains, was identified as a prime candidate for in vivo validation and formulation development. Full article

Proto-oncogenes in the RAS superfamily play dual roles in maintaining cellular homeostasis, such as regulating growth signals and contributing to cancer development through proliferation and deregulation. Activating proto-oncogenes in vitro transforms cells, underscoring their centrality in gene regulation and cellular networks. Despite decades of research, poor outcomes in advanced cancers reveal gaps in understanding Ras-driven mechanisms or therapeutic strategies. This narrative review examines RAS genes and Ras proteins in both housekeeping functions, such as cell growth, apoptosis, and protein trafficking, as well as in tumorigenesis, integrating insights from human (HRAS, KRAS, NRAS), mouse (Hras, Kras, Nras), and Drosophila melanogaster (ras) models. While RAS mutations are tightly linked to human tumors, the interplay between their standard and oncogenic functions remains complex. Even within the same tissue, distinct cancer pathways—such as the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways—can drive varied disease courses, complicating treatment. Advanced-stage cancers add further challenges, including heterogeneity, protective microenvironments, drug resistance, and adaptive progression. This synthesis organizes current knowledge of RAS gene regulation and Ras protein function from genomic alterations and intracellular signaling to membrane dynamics and extracellular interactions, offering a layered perspective on the Ras pathway’s role in both housekeeping and tumorigenic contexts. Full article