Resveratrol remains one of the most extensively studied plant-derived polyphenols because of its broad antioxidant, anti-inflammatory, cardioprotective, neuroprotective, and anticancer activities. However, its clinical translation has been substantially limited by its poor aqueous solubility, rapid phase II metabolism, and low systemic bioavailability, despite decades of intensive investigation. Structural modification through methoxylation has emerged as a promising strategy to overcome these pharmacokinetic limitations by enhancing metabolic stability, lipophilicity, membrane permeability, and biological activity. While considerable attention has focused on resveratrol and a limited number of established analogs, emerging methoxylated derivatives remain comparatively underexplored. This review highlights the structural characteristics, biological activities, and molecular mechanisms of two such derivatives, 4,4-(ethane-1,2-diyl)bis(2-methoxyphenol) (EG) and (Z)-3,5,4′-trimethoxystilbene (Z-TMS), and discusses evidence from structurally similar, better-characterized compounds that may aid in understanding their activities. Despite promising experimental findings, the therapeutic relevance of EG and Z-TMS remains insufficiently characterized because the available evidence is predominantly derived from in vitro studies, while data on toxicity, therapeutic index, long-term safety, pharmacodynamics, and clinically relevant systemic exposure remain limited. This review emphasizes the anticancer potential of these emerging methoxylated derivatives, identifies current knowledge gaps, and provides a basis for considering them as lead compounds for anticancer drug development.

Glioblastoma multiforme (GBM) remains one of the most aggressive primary brain tumors with poor prognosis despite multimodal therapy. Photodynamic therapy (PDT) using indocyanine green (ICG) is an emerging adjuvant approach aimed at eliminating residual tumor cells after resection. While ICG-PDT exerts cytotoxic effects, its impact on molecular pathways regulating programmed cell death in glioma cells is not fully understood. In this study, T98G and U-118MG glioblastoma cells were divided into four groups: untreated control, light-only (10 min broadband irradiation), ICG-only (15 min incubation), and ICG-PDT (15 min ICG + 10 min broadband irradiation). Relative mRNA expression of apoptosis-related genes (BAX, BCL2, CASP3, FAS) and ferroptosis-related genes (GPX4, ACSL4, SLC7A11, GCH1) was quantified 24 h post-treatment by RT-qPCR using the 2-ΔΔCt method. ICG-PDT significantly reduced cell viability to 67.79% ± 3.39% (vs. 86.66% ± 4.33% in control), confirming effective phototoxicity. No statistically significant differences in mRNA levels were observed for any of the investigated genes across the groups (one-way ANOVA and Kruskal-Wallis, all p > 0.05). The largest non-significant deviation was a mild decrease in GPX4 (fold change 0.87) in the ICG-PDT group. Fluctuations in GCH1 were accompanied by high variance, likely reflecting technical noise rather than a true biological trend. The mRNA BAX/BCL2 ratio remained stable (~30) across all conditions. In contrast, the U-118MG line showed greater transcriptional sensitivity, with statistically significant decreases in CASP3 (p = 0.012) and ACSL4 (p = 0.031) expression, along with downward trends in BCL2 and GPX4 following ICG-PDT. ICG-PDT does not induce significant transcriptional changes in the analyzed genes T98G at the 24 h time point under the applied experimental conditions. In U-118MG cells, moderate transcriptional engagement of both apoptotic and ferroptotic routes was observed. Further studies at the protein and functional levels, across multiple time points and models, are warranted to fully elucidate the mechanisms of ICG-PDT in glioblastoma.

Glioblastoma multiforme (GBM), isocitrate dehydrogenase (IDH)-wildtype, is the most aggressive primary malignant tumor of the central nervous system, characterized by poor prognosis and high recurrence rates despite standard multimodal treatment. This study investigates the molecular response of glioblastoma cells to 5-aminolevulinic acid (5-ALA)-based photodynamic therapy (PDT), focusing on gene expression changes associated with apoptosis, ferroptosis, and oxidative stress. Human glioblastoma T98G cells were treated with 5-ALA followed by light irradiation, and gene expression was analyzed using RT-qPCR. PDT induced moderate upregulation of pro-apoptotic genes (BAX, CASP3, FAS) alongside increased expression of the anti-apoptotic gene BCL2, indicating simultaneous activation of cell death and survival pathways. Ferroptosis-related genes showed mixed responses, with slight upregulation of ACSL4 and downregulation of GPX4, suggesting increased susceptibility to lipid peroxidation. The most significant change was observed in GCH1 expression, reflecting activation of oxidative stress response mechanisms. However, none of the observed changes reached statistical significance, likely due to the limited sample size. These findings demonstrate that PDT induces a complex and dual biological response in glioblastoma cells, involving both cytotoxic and adaptive mechanisms. This may limit therapeutic efficacy and contribute to treatment resistance. The results support the rationale for combining PDT with targeted molecular therapies aimed at inhibiting antioxidant defenses and anti-apoptotic pathways. Additionally, personalized therapeutic strategies based on tumor molecular profiles may enhance treatment outcomes. Further studies with larger sample sizes and functional validation are required to confirm these preliminary observations.

Photodynamic therapy (PDT) efficacy depends on both the photophysical properties of the photosensitizer and the spectral characteristics of the irradiation source. In this study, the photodynamic response of RAW 264.7 macrophages incubated with an indocyanine green-bovine serum albumin (ICG-BSA) complex was evaluated using three irradiation sources: an 820 nm diode laser (emission maximum ~790 nm), a 660 nm diode laser, and a broadband tungsten-halogen OSL2 illuminator. The photophysical stability of the ICG-BSA complex was assessed by UV-Vis spectroscopy, while PDT activity was evaluated by cell viability and fluorescence measurements. The ICG-BSA complex exhibited good spectral stability and maintained characteristic absorption bands associated with monomeric and dimeric forms of ICG. Irradiation induced a fluence-dependent decrease in cell viability and fluorescence intensity, indicating effective photodynamic activation and photobleaching of the photosensitizer. The strongest photodynamic response was observed for the 820 nm laser, followed by the OSL2 illuminator, whereas the 660 nm laser produced the weakest effect. Increasing ICG concentration further enhanced photodynamic cytotoxicity under constant irradiation conditions. The results demonstrate that PDT efficiency is strongly influenced by spectral overlap between the irradiation source and the absorption characteristics of the ICG-BSA complex, highlighting the importance of excitation conditions in determining photodynamic activity.

Gliomas are the most common group of primary brain tumors, among which glioblastoma multiforme (GBM) is characterized by a particularly poor prognosis and the limited effectiveness of available treatments. Ophiobolin A (OP-A), a natural sesterterpenoid, exhibits promising anticancer properties, including the ability to cross the blood-brain barrier and induce paraptosis-like cell death. However, the molecular mechanisms underlying its action, especially in the early phase of the cellular response, remain not fully understood. The aim of this study was to analyze early changes in the expression of genes associated with apoptosis, ferroptosis, and antioxidant mechanisms in T98G and U118MG glioma cells exposed to OP-A. Gene expression was assessed by RT-qPCR, apoptosis was evaluated using Annexin V/PI staining and flow cytometry, and treatment-induced morphological changes were documented by brightfield microscopy. Statistical analysis was performed using the Mann-Whitney U test. Descriptive Annexin V/PI analysis showed a lower proportion of viable cells and a higher proportion of early apoptotic cells in the analyzed OP-A-treated T98G and U118MG samples compared with the corresponding vehicle-control samples. These preliminary observations were based on technical replicates from a single biological experiment and require confirmation in independent biological replicates. Transcriptional profiling revealed a shift toward a pro-apoptotic phenotype, characterized by increased BAX and FAS expression together with a trend toward reduced BCL2 expression, whereas ferroptosis-associated genes remained largely unchanged. Notably, SLC7A11 upregulation suggested activation of compensatory antioxidant mechanisms in response to OP-A treatment. In T98G cells, OP-A induced a distinct and reproducible transcriptional signature that enabled accurate discrimination from control conditions (AUC = 0.833). Feature importance and SHAP analyses identified BAX as the most informative predictor, followed by SLC7A11 and FAS, with bootstrap validation confirming BAX as a stable marker. Pathway analysis demonstrated selective activation of apoptosis- and cysteine metabolism-related pathways, while hierarchical clustering revealed that OP-A generated a transcriptional profile distinct from oxidative stress-inducing agents. The predictive performance of this molecular signature was cell-line dependent, showing weaker discrimination in U118MG cells.Short-term OP-A exposure in T98G and U118MG cells was associated with exploratory trends in apoptosis- and redox-related gene expression and a higher proportion of Annexin V-positive cells. The machine-learning analyses identified candidate discriminatory features within this limited dataset but should be regarded as hypothesis-generating. Larger studies with independent biological replication, additional GBM models, different exposure conditions, and functional validation are required to confirm these observations and clarify the mechanism of OP-A action.

Bioactive molecules present in plant products determine their very valuable health-promoting properties. Among the plants, due to these properties, particular attention is paid to the seeds of common flax (Linum usitatissimum L.), which have been used for over 6000 years and are known for their benefits. A review of 117 scientific articles indexed in PubMed/MEDLINE, ScienceDirect, and Wiley Online Library, published between 1997 and 2024, was conducted. These seeds are characterized by a high content of valuable nutrients, such as essential omega-3 fatty acids, including α-linolenic acid (ALA), lignans, isoflavones, phytoestrogens, flavonoids, vitamins, and minerals that influence the digestive system function and have anti-cancer properties. The presence of these bioactive compounds in flaxseeds provide anti-cancer properties.

The environmental presence of excess nitrogen poses a significant threat to biodiversity, human health, and climate stability. Conversely, nitrogen deficiency can hinder our ability to sustainably provide sufficient food for the global population. The impact of nitrates and nitrites on human health is intricately tied to their concentrations in water and food sources. The aim of the following article was to summarize the data on the effects of nitrates on health, with particular emphasis on their effect on the thyroid gland. Current scientific findings indicate that these compounds can have dual effects, both beneficial and harmful, on health. Dietary nitrates are naturally abundant in fruits and vegetables or can be introduced as additives, notably in processed and cured meats. Nitrate supplementation has shown promise in enhancing physical performance, influencing gut microbiota composition, and increasing short-chain fatty acid production. Studies suggest that nitrate consumption can effectively reduce inflammation and counter the deleterious effects of oxidative stress in the body. However, the addition of nitrites as preservatives may lead to the formation of nitrosamines, known carcinogens that detrimentally impact cardiovascular and metabolic functions. Excessive nitrite intake from animal sources has been linked to an increased risk of thyroid cancer, particularly among women. Nevertheless, a moderate intake of naturally occurring nitrates from food sources demonstrates potential benefits such as blood pressure regulation, improved vascular endothelial function, and enhanced tissue insulin sensitivity. These positive effects might mitigate risk factors associated with developing complications in thyroid disease and warrant further investigation.

Adipose tissue of obese people secretes a number of adipokines, including adiponectin and resistin, which have an antagonistic effect on the human metabolism, influencing the pathogenesis of many diseases based on low-grade inflammation. Body composition analysis using bioelectrical impedance analysis (BIA) was performed in 84 adults with obesity, i.e., body mass index (BMI) greater than or equal to 30 kg/m2. Serum was collected to analyze the concentration of adiponectin (ApN) and resistin. The subjects additionally completed a food frequency questionnaire FFQ-6 and a three-day food diary. Adiponectin-resistin index (AR index) was calculated. The results show a positive correlation between resistin levels and BMI and subcutaneous fat content. AR index value was also positively associated with the amount of adipose tissue and body mass. Adiponectin level in the serum of the studied individuals decreased with the content of lean tissue. Adiponectin level also decreased with the amount of carbohydrates, amount of starch, and glycemic load of the diet. Resistin decreased in patients who frequently consumed white pasta and red meat, while AR index was positively associated with the amount of white rice and saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) consumed but negatively associated with the frequent consumption of carbohydrates, including starch. Physical activity was negatively correlated with adiponectin levels and AR index. We concluded that body composition significantly influenced serum resistin and adiponectin concentrations the AR index. Dietary components also had a significant effect.

The increasing prevalence of obesity, a chronic disease, necessitates the development and evaluation of evidence-based prevention and intervention strategies tailored to heterogeneous populations. Certain fruits, including papaya and pineapple (Ananas comosus), have been investigated as potential dietary components in obesity management. In the context of obesity and chronic low-grade inflammation, bromelain, a proteolytic enzyme derived from pineapple, is a widely studied phytotherapeutic agent that acts through multiple mechanisms intersecting immune and metabolic pathways. This narrative review summarizes current evidence on the effects of bromelain in obesity, low-grade inflammation, and related metabolic disturbances. Searches of the literature were conducted in Google Scholar, PubMed, and Scopus databases. This review incorporates findings from in vitro, animal, and human studies. We outline the mechanisms and evidence supporting the therapeutic efficacy of bromelain, emphasizing its implications for obesity management in clinical settings. Bromelain has been shown to exert significant anti-inflammatory activity and may modulate adipocyte metabolism, potentially alleviating comorbidities associated with excess adiposity. Although its effects on immune cells are relatively well described, the mechanisms underlying bromelain’s actions on adipocytes remain incompletely understood.

Background: The cannabinoid receptor (CBR) plays a significant role in oogenesis, pregnancy, and childbirth. It might also play a significant role in preterm birth (PTB). The aim of the study was to investigate the association between the expression of the CBR in the placenta and the incidence of PTB.Methods: This prospective, observational, multicentre preliminary study was conducted on placental samples obtained from 109 women. The study included 95 patients hospitalized due to the high risk of PTB. They were divided into two groups: Group 1, where the expression of the CBR1 and CBR1a was analyzed, and Group 2, in which we examined CBR2 expression. The control group, that is, Group 3, consisted of 14 women who delivered at term, and their placentas were tested for the presence of all three receptor types (CBR1, CBR1a, and CBR2).Results: The study used reverse transcription and real-time PCR methods to assess the expression of CBRs in the placental tissues. The expression of the CBR2, CBR1, and CBR1a receptors was significantly lower in the placentas of women after PTB compared to those after term births, p=0.038, 0.033, and 0.034, respectively.Conclusions: The presence of CBR mRNA in the human placental tissue was confirmed. The decreased expression of CBRs could serve as an indicator in predicting PTB.

INTRODUCTION Long noncoding RNAs (lncRNAs) have long been considered molecular noise within the transcriptome, but over time it has been shown that they perform many important biological func- tions and are associated with various inflammatory and autoimmune diseases, including rheumatoid arthritis (RA). OBJECTIVES The aim of this study was to evaluate the association between the circulating lncRNAs and RA activity. PATIENTS AND METHODS The study included 63 patients with well -established RA (median disease duration of 12 years), at a mean (SD) age of 51.7 (13) years, 88.9% women, and 25 healthy controls (HCs) at a mean (SD) age 51.8 (8.2) years, 80% women. Quantitative real -time polymerase chain reac- tion was used to evaluate the plasma concentration levels of 6 lncRNAs: PACERR, NEAT1, HOTTIP, GAS5, MALAT1, and HIX003209. RESULTS Among the tested molecules, 5 targets (PACERR, NEAT1, HOTTIP, GAS5, and HIX003209) had lower concentrations in the RA patients than in the HCs. LncRNAs for NEAT1, PACERR, and GAS5 showed differences between the severe disease activity group (the 28 joint disease activity score [DAS28] / erythrocyte sedimentation rate >5.1) and HCs (P = 0.02, P = 0.003, and P = 0.04, respec- tively). The multiple linear regression analysis indicated that GAS5 had the greatest impact on the disease activity based on DAS28 (P = 0.01). CONCLUSIONS Circulating plasma lncRNAs may be considered as supporting molecular markers associ- ated with RA activity and may be useful in identifying the disease exacerbation.

Introduction: The low-grade inflammation occurring in obese individuals leads to many diseases, including cardiovascular disease (CVD). Dietary patterns, food groups or nutrients in a well-balanced diet may reduce the level of pro -inflammatory markers and the risk of obesity -related morbidities. Our study aims to describe three cytokines in obese patients in relation to dietary habits, lifestyle and body composition. Material and methods: Serum samples were collected from 84 obese adult volunteer subjects [body mass index (BMI) >= 30 kg/m 2 ] to analyze the concentrations of interleukin 6 (IL -6), tumor necrosis fac - tor alpha (TNF- alpha ) and interferon gamma (IFN- gamma ). The subjects were tested by bioelectrical impedance analysis (BIA) and completed a three-day food diary and original questionnaire with the FFQ-6 food consump - tion frequency questionnaire. Results and conclusions: Higher serum levels of IL -6 and IFN- gamma were found in patients with ath - erosclerosis, but the group was too small for a reliable correlation. Subcutaneous but not visceral ad - ipose tissue correlated positively with IL -6 levels. Dietary factors such as amount of sugars, including galactose and sucrose, in the diet and the frequency of consumption of sweet flavored dairy products correlated positively with the levels of IL -6 and TNF- alpha , while the frequency of alcohol consumption negatively correlated with the level of IL -6. The greater the frequency of sports, the higher was the level of IL -6. In obese individuals, the level of pro -inflammatory cytokines could predispose to atherosclerosis and is associated with dietary factors and lifestyle.

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disorder, characterized by progressive heterotopic ossification (HO) and painful soft-tissue inflammatory flare-ups. This was a post hoc analysis from a phase 2 (NCT03188666) trial in which adults with FOP received intravenous anti-activin A antibody garetosmab 10 mg/kg or placebo every 4 wk over 28 wk (Period 1), followed by a 28-wk open-label treatment and extension (Periods 2 and 3). Here we describe flare-ups, their relationship to new HO lesions, and the impact of garetosmab on flare-ups. Volume of new HO lesions was measured by CT. Patient-reported flare-ups were defined by any 2 of the following: new onset of pain, swelling, joint stiffness, decrease in movement, or perceived presence of HO. Flare-ups were experienced by 71% (17/24) of placebo-treated patients, 59% (10/17) of whom developed a new HO lesion irrespective of flare-up location; 24% of flare-ups location-matched new HO lesions. Twenty-nine new HO lesions occurred in the placebo cohort by week 28, of which 12 (41%) occurred in the same location as new or ongoing flare-ups. A higher volume of newly formed heterotopic bone (week 28) occurred in placebo-treated patients who had experienced a prior flare-up vs those without (median [Q1:Q3] of 16.6 [12.0:31.1] vs 3.2 cm3). Garetosmab was previously shown to decrease patient-reported flare-up frequency in Period 1; here, garetosmab reduced the median (Q1:Q3) duration of patient-reported flares (15.0 [6.0:82.0] vs 48.0 [15.0:1.00] d) and the severity of flare-ups vs placebo. Frequency of corticosteroid use was numerically reduced in those treated with garetosmab (40.0%) vs placebo (58.3%). In this analysis, 71% of placebo-treated adults with FOP experienced flare-ups over 28 wk, which were associated with an increased volume of newly formed heterotopic bone. Garetosmab reduced the severity and duration of flare-ups, with effects sustained during the entire trial.

Black garlic (BG) is a fermented form of garlic (Allium sativum L.), produced at precisely defined temperatures, humidities, and time periods. Although garlic has been used for thousands of years, black garlic is a relatively new discovery. There are many bioactive compounds in black garlic that give it medicinal properties, including anti-inflammatory and anti-cancer properties. In our review article, we present scientific studies examining the anti-inflammatory and anti-cancer effects of black garlic. According to research, this effect is mainly due to the reduction in the production of pro-inflammatory cytokines, as well as the ability to scavenge free oxygen radicals and induce apoptosis. In addition, the phytochemicals contained in it have antiproliferative and antiangiogenic properties and inhibit the growth of cancer cells. Black garlic is a valuable source of biologically active substances that can support anti-inflammatory and anti-cancer therapy. Compared to Allium sativum, black garlic has fewer side effects and is easier to consume.