Search Results (190)

Natural compounds, particularly flavonoids, have emerged as promising anticancer agents due to their various biological activities and no or negligible toxicity towards healthy tissues. Among these, isorhamnetin, a methylated flavonoid, has gained significant attention for its potential to target multiple cancer hallmarks. This review comprehensively explores the mechanisms by which isorhamnetin exerts its anticancer effects, including cell cycle regulation, apoptosis, suppression of metastasis and angiogenesis, and modulation of oxidative stress and inflammation. Notably, isorhamnetin arrests cancer cell proliferation by regulating cyclins, and CDKs induce apoptosis via caspase activation and mitochondrial dysfunction. It inhibits metastatic progression by downregulating MMPs, VEGF, and epithelial–mesenchymal transition (EMT) markers. Furthermore, its antioxidant and anti-inflammatory properties mitigate reactive oxygen species (ROS) and pro-inflammatory cytokines, restricting cancer progression and modulating tumor microenvironments. Combining isorhamnetin with other treatments was also discussed to overcome multidrug resistance. Importantly, this review integrates the recent literature (2022–2024) and highlights isorhamnetin’s roles in modulating cancer-specific signaling pathways, immune evasion, tumor microenvironment dynamics, and combination therapies. We also discuss nanoformulation-based strategies that significantly enhance isorhamnetin’s delivery and bioavailability. This positions isorhamnetin as a promising adjunct in modern oncology, capable of improving therapeutic outcomes when used alone or in synergy with conventional treatments. The future perspectives and potential research directions were also summarized. By consolidating current knowledge and identifying critical research gaps, this review positions Isorhamnetin as a potent and versatile candidate in modern oncology, offering a pathway toward safer and more effective cancer treatment strategies. Full article

The advantages of extra virgin olive oil (EVOO) intake as part of a varied, healthy and balanced diet were demonstrated by many epidemiological studies. In particular, several components present in EVOO, such as tocopherols, carotenoids and phenolic compounds, play an important protective role in mitigating inflammatory diseases, atherosclerosis, neurodegenerative diseases and cancer. The protective effect exerted by EVOO was proposed to be accounted for by its antioxidant, anti-inflammatory or anti-proliferative properties. The present review will focus on the interactions among EVOO’s components and pro-inflammatory cytokines, aiming to reveal the mechanisms potentially involved in the anticancer action of EVOO. Cancer patients very frequently develop a devastating syndrome known as cachexia, which negatively impinges on their outcome. The main features of cachexia include progressive body weight loss, fat and muscle wasting, and dysmetabolism, all of which partially result from the onset of systemic inflammation. In this regard, the possibility that EVOO could be beneficial to cancer patients by mitigating cachexia will be reviewed, focusing on the skeletal muscle. Full article

Background/Objectives: We evaluated the efficacy of a good lifestyle intervention on the severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in children with Down syndrome (DS). Methods: This retrospective longitudinal study included 31 children with Down syndrome (DS) who were affected by MASLD and attended nutritional counseling based on a nutritional approach (e.g., Mediterranean diet and antioxidant supplements), as well as physical exercise. Clinical parameters, markers of low-grade systemic inflammation, and hepatic steatosis, as assessed by ultrasound, were evaluated at baseline (T0) and after 6 months (T1). Results: Several anthropometric and biochemical parameters, including body mass index, waist circumference, diastolic and systolic blood pressure, aspartate aminotransferase, basal insulin, insulin resistance, pro-inflammatory interleukin-1β, and anti-inflammatory interleukin-10, showed significant improvement after 6 months of a nutritional approach. This study also found a regression of at least one grade of hepatic steatosis in a significant portion of patients, especially in those who received antioxidant supplements. Conclusions: Our study further supports the hypothesis that a healthy lifestyle intervention, based on adherence to the Mediterranean diet, natural supplements with antioxidant properties, and regular physical activity, can be considered a safe therapeutic approach for reducing the risk and severity of MASLD in children with DS. Full article

The main objective of proton beam therapy is to precisely irradiate diseased tissue while minimizing damage to healthy cells. For effective treatment, the linear energy transfer (LET) is a key parameter in ensuring the destruction of diseased cells, and both the dose and LET are typically represented as functions of depth. The distribution of dose and LET in the target depends on the beam properties, including beam energy, energy spread, beam size, and beam emittance. The aim of this work is to present the method used to characterize the proton beam properties obtained from the machine employed in the simulation and to determine the dose and dose-averaged LET (LET_d) values, including their peak positions in depth. These results are used to predict the dose and LET_d at different depth positions under experimental conditions. We utilized GEANT4, a Monte Carlo (MC) simulation-based software, to examine the integral depth-dose position and the peak position of the LET_d. The proton source was obtained from a cyclotron accelerator, specifically the Varian ProBeam Compact spot scanning system at King Chulalongkorn Memorial Hospital in Bangkok, Thailand. The system provides proton energies ranging from 70 MeV to 220 MeV. In this study, four proton energies—70 MeV, 100 MeV, 150 MeV, and 220 MeV—were chosen to characterize the beam properties. The 80%–20% distal fall-off obtained from the simulation was used to determine the energy spread for each selected energy by matching the depth-dose peak with the measurement data. The optimal energy spreads were found to be 1.5%, 1.25%, 1%, and 0.5% for proton energies of 70 MeV, 100 MeV, 150 MeV, and 220 MeV, respectively. These energy spreads ensure that the difference in the depth-dose profile is below 1% when comparing the simulated and measured depth-dose profiles. Furthermore, the peak LET_d was found to be approximately 1 mm away from the R₈₀ position, a depth that corresponds to 80% of maximum dose, for each energy. This information can be used to guide the desired LET_d position by utilizing the R₈₀ depth position. Full article

To further extend the structure–activity relationships on previously identified anti-proliferative imidazo-pyrazoles, a novel series of compounds was designed and synthesized. In the obtained derivatives (1), the imidazo-pyrazole scaffold was formally condensed with a substituted triazole moiety, known for its biological properties. All derivatives were tested for anti-proliferative activity on a panel of 60 different cancer cell lines and compound 1h was identified as the most promising derivative, being highly effective against melanoma cells. Additional investigations demonstrated a cytotoxic and pro-oxidant action of the compound 1h on human metastatic melanoma cell lines (MeOV and MeTA) but not on healthy keratinocytes (HaCAT), confirming the selective activity of the compound. In silico calculations predicted favorable drug-like and pharmacokinetic properties and pre-formulation studies evaluated the effect of Tween 80 on 1h solubility. Overall, the collected data confirmed the pharmacological potential of the imidazo-pyrazole scaffold and indicated 1h as an interesting lead structure for the development of novel anti-melanoma agents. Full article

Cisplatin is a widely utilized chemotherapy drug effective against various cancers, yet its use is often constrained by severe toxicity to healthy organs, including the liver, kidneys, and spleen. This study explored the protective role of Chlorella vulgaris, a microalga known for its antioxidant and anti-inflammatory properties, against cisplatin-induced organ damage. The research focused on modulating oxidative stress, inflammation, and the Nrf2 signaling pathway. The experimental design included four groups: a control group receiving saline, a cisplatin group administered 1.34 mg/kg weekly for three months, a C. vulgaris group receiving 150 mg/kg daily, and a combined cisplatin/Chlorella vulgaris group. Cisplatin treatment significantly elevated oxidative stress markers, such as lipid peroxidation and nitric oxide, while increasing pro-inflammatory cytokines (TNF-α, IL-12, IL-6) and reducing antioxidant capacity. Additionally, liver and kidney function markers were markedly impaired, and histopathological analysis revealed structural damage in the liver, kidneys, and spleen. Conversely, C. vulgaris supplementation mitigated these effects, restoring oxidative stress markers, cytokine levels, and organ function to near-normal values. Microscopic examination confirmed that Chlorella vulgaris effectively prevented cisplatin-induced structural damage. Notably, while cisplatin increased Nrf2 expression as an adaptive response to oxidative stress, C. vulgaris attenuated this effect, reflecting its potent antioxidant capabilities. Full article

Background: Adipokines secreted by the adipose tissue and placenta play a critical role in regulating metabolic functions that are essential for fetoplacental development and embryonic growth. While adipokines are known to impact a wide range of physiological and pathological conditions, their role in affective disorders during pregnancy remains underexplored. In this study, we aimed to assess the serum levels of distinct adipokines and examine their association with anxiety and comorbid depression in pregnant women. Methods: Third-trimester pregnant women with severe anxiety (ANX, n = 45) and anxiety plus depressive symptoms (ANX + DEP, n = 61) were enrolled in the study, along with healthy control subjects (CTRL, n = 33). Participants were classified using the Hamilton Anxiety Rating Scale (HARS) and the Hamilton Depression Rating Scale (HDRS). Serum levels of adiponectin, adipsin, leptin, and resistin were quantified by flow cytometry-based immunoassay. Clinical, biochemical, and demographic parameters were analyzed using ANOVA with a post hoc Tukey test. Pearson bivariate and partial correlations were performed to assess associations between variables. Results: Adipokine serum levels were significantly higher in the symptomatic groups (ANX, ANX + DEP) than in the CTRL group (p < 0.001). Adiponectin, leptin, and resistin levels positively correlated with anxiety symptoms (HARS, p < 0.01). Furthermore, resistin levels showed a strong association with depressive symptoms (HDRS, p = 0.001) in the ANX + DEP group, after adjusting all parameters by clinical confounders. Conclusions: Our findings revealed that both pro- and anti-inflammatory adipokine levels are elevated in women with affective symptoms during late pregnancy. Pro-inflammatory properties of leptin and resistin may contribute to the severity of anxiety symptoms. Notably, resistin emerges as a key adipokine associated with the expression of depressive symptoms. In addition, adiponectin, acting as an anti-inflammatory mediator, may counteract the inflammatory responses induced by leptin and resistin. These results provide new insights into the role of specific adipocytokine in women with affective disorders during late pregnancy. Full article

Zearalenone (ZEA), a mycotoxin primarily generated by the Fusarium species, constitutes a prevalent contaminant in both human and animal feedstuffs. Chronic exposure to this mycotoxin induces hepatic inflammatory responses in livestock species including rabbits, ultimately leading to organ damage. Selenomethionine (SeMet), an organic selenium source recognized for its antioxidant properties and anti-inflammatory bioactivity, demonstrates protective benefits in animals through its detoxification mechanism and growth promotion. The present study investigated the protective effect of SeMet against ZEA-induced hepatic inflammation and elucidated its underlying mechanisms. Fifty healthy 90-day-old rabbits were randomly divided into five groups: control, ZEA-exposed and three SeMet-supplemented groups receiving 0.2, 0.35 or 0.5 mg/kg via dietary inclusion. After two weeks of SeMet pretreatment, ZEA administration (1.2 mg/kg B.W.) was imitated via oral gavage daily for one week in both the ZEA group and three SeMet-treated groups. As a result, ZEA exposure induced the significant structural disruption of the hepatic lobules, accompanied by increased collagen deposition, elevated pro-inflammatory cytokine profiles (IL-6, IL-1β, TNF-α) and reduced anti-inflammatory mediator levels (IL-10, TGF-β). SeMet supplementation alleviated ZEA-induced histological alterations, including inflammatory cell infiltration and collagen accumulation. Biochemical analysis indicated the restoration of inflammatory markers to near-normal levels when treated with SeMet. Notably, immunohistochemical results showed that SeMet significantly reduced the protein levels of IL-6 and its downstream target STAT3 under ZEA exposure. These findings indicated that SeMet attenuated ZEA-induced hepatic inflammation by modulating the IL-6/STAT3 signaling axis, with dietary supplementation of 0.35 mg/kg SeMet exhibiting the most significant effect on alleviating ZEA-induced hepatic inflammatory injury. Full article

Ovotransferrin (OVT) is one of the major proteins of egg white and is known to bind and transport irons in animals. OVT exerts bacteriostatic and bactericidal activities due to its iron-binding capacity. OVT effectively controls the growth of various pathogenic microorganisms, including Pseudomonas, E. coli, Staphylococcus, Proteus, and Klebsiella species, as well as inhibiting the replication of viruses. OVT also has antioxidant, anti-inflammatory, anti-hypertensive, anticancer, and immuno-stimulating properties. For instances, OVT quenches free radicals, induces antioxidant enzymes, suppresses pro-inflammatory cytokines, increases immune cells, reduces angiotensin-converting enzymes, and inhibits the proliferation of cancer cells. In this review, the beneficial effects of OVT in both in vitro and in vivo, particularly livestock, are described. Because of its antimicrobial properties, OVT supplementation in livestock feed would be an excellent alternative to antibiotics, which reducing the development of antibiotic-resistant pathogenic microorganisms. Thus, OVT could be a game-changing protein for the growth, performance, and healthy life of animals. Full article

Background: Autophagy, a catabolic process essential for maintaining cellular homeostasis, declines with age and unhealthy lifestyles, contributing to neurodegenerative diseases. Probiotics, including Milmed yeast, have demonstrated anti-inflammatory and antioxidant properties. This study evaluated the activity of Milmed on BV-2 microglial cells in vitro and in the in vivo model of Caenorhabditis elegans (C. elegans) in restoring autophagic processes. Methods: BV-2 microglial cells were incubated with S. cerevisiae (Milmed treated yeast or untreated yeast) and then stimulated with lipopolysaccharide (LPS). mRNAs of the autophagic factors and antioxidant enzymes were assessed by qPCR; mTOR and NRF2 were evaluated by ELISA. pNRF2 compared with cytosolic NRF2 was evaluated by immunofluorescence. The longevity, body size, and reactive oxygen species (ROS) levels of C. elegans were measured by fluorescence microscopy. Results: Treatment with Milmed YPD cultured yeast or the dried powder obtained from it promoted autophagic flux, as shown by the increased expression of the Beclin-1, ATG7, LC3, and p62 mRNAs and the inhibition of mTOR, as evaluated by ELISA. It also enhanced the antioxidant response by increasing the expression of NRF2, SOD1, and GPX; moreover, pNRF2 expression compared with cytosolic NRF2 expression was enhanced, as shown by immunofluorescence. Milmed dietary supplementation prolonged the survival of C. elegans and reduced the age-related ROS accumulation without changing the expression of gst-4. The pro-longevity effect was found to be dependent on SKN-1/Nrf2 activation, as shown by the absence of benefit in skn-1 mutants. Conclusions: Milmed yeast demonstrates significant pro-autophagy and antioxidant activity with significant pro-longevity effects in C. elegans, thereby extending the lifespan and improving stress resistance, which, together with the previously demonstrated anti-inflammatory activity, highlights its role as a highly effective probiotic for its beneficial health effects. Activation of the SKN-1/NRF2 pathway and the modulation of autophagy support the therapeutic potential of Milmed in neuroprotection and healthy aging. Full article

Systemic sclerosis (SSc) is an autoimmune disease of unknown aetiology characterised by vasculopathy with progressive fibrosis of the skin and internal organs. Tissue fibrosis is driven by activated fibroblasts (myofibroblasts) with exacerbated contractile and secretory properties. We previously reported that the long non-coding RNA HOTAIR is a key driver of SSc fibroblast activation. HOTAIR interacts with the chromatin modifiers, the polycomb repressor complex (PRC2) and coREST complex, promoting expression of pro-fibrotic genes. In this study, we show that acute activation of dermal fibroblasts from healthy subjects or SSc patients with transforming growth factor-β and other fibrotic stimuli requires the activity of the lysine-specific demethylase 1 (LSD1) subunit of the co-REST complex. Unexpectedly, LSD1 catalytic activity plays a minor role in fibrotic gene expression in HOTAIR-overexpressing fibroblasts and in maintenance of the stable myofibroblast phenotype of SSc fibroblasts. However, silencing of LSD1 in SSc fibroblasts has a profound effect on pro-fibrotic gene expression, supporting a non-canonical scaffolding function. Our study shows for the first time an essential non-canonical role for LSD1 in pro-fibrotic gene expression in SSc; however, given that this function is insensitive to LSD1 inhibitors, the therapeutic opportunities will depend on future identification of a targetable mediator. Full article

Plant extracts are increasingly becoming an answer to expensive, high-dose, synthesized chemotherapy, with milder side effects and easier accessibility. Many botanical plants contain active ingredients, such as terpenoids and alkaloids, which may combat cancer; however, studies need to be performed to test whether they are solely effective enough and whether the extracted compounds are selective for the tumor itself. Many chemotherapy drugs were initially of botanical origin, such as vincristine from Catharanthus roseus and paclitaxel from the Taxus baccata tree. The objective of this review is to assess the mechanisms of herbal therapeutics in their role against malignancy. Ajwa, curcumin, ginseng, lycopene, and ursolic acid were all respectively evaluated in the paper for their prevalent properties, their method of extraction, notable usage in medicine, which pathways they activate, and whether the transductions can disrupt cancer formation or proliferation. The findings from the review demonstrated that all the therapeutics exhibited pro-apoptotic behavior, Ajwa and curcumin exerted cell cycle arrest upon neoplasms, and Ajwa, curcumin, and lycopene showed anti-metastatic behavior. Most extracts were tested on colorectal cancer, and the pathways most commonly applied were through BAX/Bcl2 and endoproteases, such as caspase-3 and caspase-9, indicating predominantly mitochondrial apoptosis. In addition, cell cycle arrest was noted to occur during the G2/M phase via Wnt/β-catenin in both curcumin and ginseng, independently of the Wnt/β-catenin pathway in Ajwa constituents, reducing cell viability. All of these studies were demonstrated in vitro within varieties of single cell cultures, which did not take into account bioavailability nor properly demonstrate the tumor microenvironment, which may not yield the same results in vivo. Clinical trials need to be undergone to appropriately test effective dosages, as if a compound is strongly pro-apoptotic, it may not be selective just to tumor cells but also to healthy cells, which may impair their functions. Full article

Background: Microencapsulation improves the storage, handling, and administration of probiotics by protecting them from environmental factors and adverse conditions in the gastrointestinal tract. This process facilitates their controlled delivery in the body, which can simplify their use in therapies without compromising their therapeutic efficacy. Objectives: This study investigates the microencapsulation of Lactiplantibacillus plantarum LM-20, its probiotic properties, and its effects in a murine model of ulcerative colitis. Methods/Results: Synbiotic microencapsulation was carried out using spray drying with maltodextrin, gum Arabic, and inulin, achieving an encapsulation efficiency of 90.76%. The resulting microcapsules exhibited remarkable resistance to simulated gastrointestinal conditions in vitro, maintaining a survival rate of 90%. The drying process did not compromise the probiotic characteristics of the bacteria, as they demonstrated enhanced auto-aggregation, hydrophobicity, and phenol tolerance. The therapeutic potential of the microencapsulated synbiotic was evaluated in a murine model of dextran sodium sulfate-induced ulcerative colitis. The results revealed that mice treated with microencapsulated Lactiplantibacillus plantarum LM-20 showed an 83.3% reduction in the disease activity index (DAI) compared to the ulcerative colitis control group. Moreover, a significant decrease was observed in pro-inflammatory cytokine levels (IL-1β and TNF-α) and myeloperoxidase activity, with values comparable to those of the healthy control group. Conclusions: These findings suggest that microencapsulated Lactiplantibacillus plantarum LM-20 could be a promising candidate for therapeutic applications in the prevention and management of ulcerative colitis. Full article

Background/Objectives: We aimed to examine the acute effects of deep breathing exercise and transcutaneous auricular vagus nerve stimulation (taVNS) on autonomic nervous system activation and the characteristics of certain muscle groups and to compare these two methods. Methods: 60 healthy adults between the ages of 18 and 45 were randomly divided into two groups to receive a single session of taVNS and deep breathing exercises. Acute measurements of pulse, blood pressure, perceived stress scale, autonomic activity, and muscle properties were performed before and after the application. Results: A significant decrease was detected in the findings regarding the perceived stress scale, pulse, and blood pressure values as a result of a single session application in both groups (p < 0.05). In addition, it was determined that the findings regarding autonomic measurement values increased in favor of the parasympathetic nervous system in both groups (p < 0.05). In measurements of the structural properties of the muscle, the stiffness values of the muscles examined in both groups decreased (p < 0.05), while the findings regarding relaxation increased (p < 0.05), except for the masseter in the deep breathing (DB) group. As a result of the comparative statistical evaluation between the groups, the increase in parasympathetic activity was found to be greater in the DB group according to root mean square of differences in successive RR intervals (RMSSD), the percent of differences in adjacent RR intervals > 50 ms (pNN50), and stress index parameters (p < 0.05). In the measurements made with the Myoton^®PRO device, the increase in the relaxation value was higher in the gastrocnemius muscle of the VNS group (p < 0.05). Conclusions: It has been observed that both methods can increase parasympathetic activity and muscle relaxation in healthy people in a single session. However, DB appears to be slightly superior in increasing parasympathetic activity, and VNS appears to be slightly superior in increasing relaxation. Full article

Rheumatoid arthritis (RA) is a long-term systemic autoimmune disorder that causes joint inflammation, swelling, pain, bone erosion, and deformities. Recent findings emphasize the anti-inflammatory and antioxidant properties of bioactive natural compounds, such as polyphenols extracted from plants and fruits, and their possible synergistic effect when used in combination with current therapies to improve the prognosis and symptoms of inflammatory rheumatic diseases. Here, we report that Sicilian extra virgin olive oil polyphenol-enriched extracts (PE-EVOOs) reduce intracellular reactive oxygen species (ROS) and pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β), in peripheral mononuclear cells (PBMCs) obtained from both RA patients and healthy subjects (HSs) treated with lipopolysaccharides (LPS) as a control. HPLC-ESI-MS analysis highlighted that PE-EVOOs are rich in different polyphenolic compounds responsible for many of the observed biological effects. At molecular levels, Western blotting analyses revealed that PE-EVOO treatment is associated with the downregulation of the phosphorylated and active form of the inflammatory transcription factor NF-κB and the pro-inflammatory enzyme cyclooxygenase 2 (COX2). In addition, PE-EVOOs upregulated the transcription factor Nrf2 and its target antioxidant enzyme catalase and manganese superoxide dismutase (MnSOD). Collectively, these results suggest a possible use of PE-EVOOs as potential adjuvants for the treatment of RA. Full article