Fulltext search in archive

Acute rejection (AR) following heart transplantation (HTx) is a common complication, especially in the early post-HTx period. Mitochondrial DNA (mtDNA), released into circulation from stressed mitochondria, mimics ongoing immune activation and facilitates the release of pro-inflammatory substances. Our study aimed to assess cell-free mtDNA levels to identify early indicators of acute rejection progression. The absolute concentration of cf-mtDNA (cp/μl) was measured in 77 adult patients using quantitative polymerase chain reaction. Blood samples (n = 300) were collected before their corresponding biopsy according to the timeline within the first year post-HTx. The median cf-mtDNA levels in samples with confirmed AR (n = 57) was higher compared to samples without diagnosed rejection (n = 210; Padj < 0.01). When acute cellular (ACR; n = 39) and antibody-mediated rejection (AMR; n = 18) were analyzed separately, only AMR demonstrated higher levels compared to samples without diagnosed rejection (Padj = 0.02). The highest cf-mtDNA levels were detected in samples collected during early post-HTx complications compared to samples without rejection and AR samples (for both Padj < 0.0001). Both ACR and AMR were observed throughout the one-year period, with the majority (3rd quartile) occurring during the first 200 days post-HTx. Post-HTx complications, such as graft dysfunction or acute kidney injury, were observed within the first 11 days, with the majority (71.4%) occurring within 5 days post-HTx. The presence of AR, and specifically AMR, is associated with elevated levels of cf-mtDNA. The increase in plasma cf-mtDNA levels strongly reflects the occurrence of early complications following HTx.

Xanthine oxidoreductase (XOR) is an oxidant enzyme that exists mainly in two distinct forms: the dehydrogenase form [xanthine dehydrogenase (XDH)] and the oxidized form [xanthine oxidase (XO)]. XO might contribute to tumorigenesis through direct metabolic activation of carcinogens and indirect generation of free radicals. Oxidative stress is one of the leading causes of bladder cancer (BC). Smoking and genetic susceptibility are also linked to oxidative stress and BC. This study investigated the association between XO serum levels and XOR genetic polymorphisms with BC. A case-control study was conducted among 109 BC patients and 109 controls matched by age, gender, body mass index, and smoking status. Serum levels of XO and 8-hydroxy-2'-deoxyguanosine (8-OhdG) were measured using ELISA, while thiobarbituric acid reactive substances (TBARS) and protein carbonyl (PC) were assessed using colorimetric assays. XOR single nucleotide polymorphisms were analyzed via tetra-primer ARMS-PCR. XO levels were significantly higher in BC patients than in controls [(5.11 ± 0.28 vs 3.83 ± 0.23) ng/ml, respectively (p < 0.0006)]. Among smokers, XO levels were also elevated in BC cases compared with controls [(5.29 ± 0.35 vs 3.41 ± 0.28) ng/ml, respectively (p < 0.0001)]. Oxidative stress biomarkers were elevated in BC patients compared with controls: 8-OHdG (19.39 ± 1.37 vs 16.32 ± 1.37 nmol/l), PC (8.88 ± 0.56 vs 4.42 ± 0.56) nmol/mg of protein, and TBARS (4.23 vs 3.15) µmol/ml, respectively (p < 0.05). Haplotype analysis showed that TGTCA, TGTA, TGA, and GTA were more frequent in BC patients and associated with increased BC status [4.17 (1.16-15.00), 1.84 (1.11-3.05), 1.62 (1.01-2.60), and 1.66 (1.02-2.71) fold increase in risk, respectively (p < 0.05)]. Elevated XO and oxidative stress markers are associated with BC, supporting their role in BC pathogenesis. Our findings suggest that they may act as potential diagnostic or therapeutic targets. However, mechanistic studies are required to clarify whether XO/oxidative stress markers contribute directly to carcinogenesis or reflects general redox imbalance in malignancy. Specific XOR haplotypes might serve as biomarkers for BC.

Effect of UV irradiation on free radicals in different types of melanins and melanin complexes with diamagnetic Cd(II) and paramagnetic Cu(II) was examined by the use of electron paramagnetic resonance (EPR) spectroscopy. The aim of this studies was to compare o-semiquinone free radicals formation in two model eumelanins synthesized from 3,4-dihydroxyphenylalanine (DOPA) and tyrosine in the presence of tyrosinase, and in synthetic pheomelanin, under exposition on ultraviolet, because of the important role of free radicals and melanins in human organism. UV may change free radical concentrations in melanin. Changes in EPR spectra of DOPA-melanin-Cd(II) and DOPA-melanin-Cu(II) complexes after UV irradiation were determined. Diamagnetic Cd(II) strongly increased free radical concentrations in DOPA-melanin. UV irradiation during 30 and 60 min slightly increased and decreased free radical concentrations in DOPA-melanin-Cd(II) complexes, respectively. Paramagnetic Cu(II) quenched free radical lines of DOPA-melanin, and only the Cu(II) signals were detected for both UV-irradiated and nonirradiated samples. Free radical concentration in both eumelanins increased after UV irradiation, but it decreased in irradiated pheomelanin. EPR spectra of free radicals in the studied samples were homogeneously broadened. Slow spin-lattice relaxation processes exist in all the examined melanins and DOPA-melanin-Cd(II) complexes. Fast spin-lattice relaxation processes characterized Cu(II) in DOPA-melanin-Cu(II) complexes.

Atherosclerotic cardiovascular disease (ASCVD), including myocardial infarction and ischemic stroke, is a leading cause of death and disability worldwide and is expected to rise further by 2030. Once limited to industrialized nations, atherosclerosis has become a global issue due to the epidemiological transition from infectious to chronic metabolic diseases. Lipoproteins (chylomicrons, VLDL, LDL, HDL) and apolipoproteins play key roles in lipid metabolism and atherosclerosis development. Macrophages in plaques influence inflammation and plaque stability, with iron homeostasis also impacting disease progression. Therapies include personalized diets, statins, niacin, omega-3s, fibrates, and antiplatelet agents. Innovative strategies involve natural products and nanotechnology for targeted drug delivery, especially to macrophages and the endothelium, reducing systemic side effects. In summary, advancing therapies based on molecular insights and patient-specific factors are essential to combat this widespread chronic disease.

Aim: This study aimed to investigate the phytochemical composition of Psychotria montana extract (PME) and evaluate its inhibitory effects on MCF7 breast cancer cells. Methods: The chemical composition of PME was analyzed using UPLC-QToF-MS. The effects of PME on cell proliferation were evaluated using the MTT assay. Flow cytometry was used for cell cycle and apoptosis analysis. The effects of PME on the transcription of cell cycle control genes were assessed using real-time PCR. Results: UPLC-QToF-MS analysis revealed major compounds of PME, including terpenoids and flavonoids, with the potential to inhibit proliferation, migration, and induce apoptosis in MCF7 cancer cells. PME effectively suppressed MCF7 cell proliferation under 2D culture, with a low IC50 value of 34.7 µg/ml. PME also hindered cell migration (p < 0.01) and reduced spheroid number (p < 0.001) and size (p < 0.001) in serum-free 3D culture. Apoptosis analysis via nuclear staining with DAPI and flow cytometry revealed an increase in the number of apoptotic cells after PME treatment (p < 0.001). Additionally, the PME induced cell cycle arrest at the G0/G1 phase (p < 0.05). PME altered the expression of cell cycle control genes (cyclins and CDKs) as well as cancer suppressor genes including p16, p27, and p53 at the transcriptional level (mRNA). The results of molecular docking suggest that the compounds present in PME exhibit a high binding affinity for CDK3, CDK4, CDK6, and CDK8 proteins, which are essential regulators of the cell cycle. Conclusion: Psychotria montana has the potential to inhibit cancer cells by inducing apoptosis and halting the cell cycle of MCF7 breast cancer cells

Oxygen plays an important role in the metabolism of all tissues. The level of oxygen in the environment of melanin biopolymer in human body may change toxic effects resulted from free radicals formation in melanin-drug complexes.
Using electron paramagnetic resonance (EPR) spectroscopy we measured the effect of molecular oxygen on concentration and properties of free radicals in 3,4-dihydroxyphenylalanine-melanin (DOPA-melanin) complexes with streptomycin. Studies have shown that free radical properties of melanin are heavily dependent on the presence of oxygen in the environment of the sample. Streptomycin increases the concentration of free radicals in DOPA-melanin but in the presence of oxygen this concentration is reduced.
The EPR studies confirmed the existence of stable o-semiquinone free radicals (∼10¹⁸-10¹⁹ spin/g) in DOPA-melanin-streptomycin complexes, both in air and in vacuum, and the formation of quasi-chemical bonds between the DOPA-melanin-streptomycin complexes and oxygen molecules, which are responsible for the decrease in the concentration of free radicals. Our study showed that oxygen exerts an influence on spin-spin and spin-lattice interactions in the investigated complexes. Such effects can also be expected in a living organism, because DOPA-melanin is a model eumelanin mainly present in human tissues.

Introduction: The gut-spleen axis has been proposed to link the gut environment with splenic immune regulation and systemic homeostasis. This scoping review examines this interaction in rodent models. Methods: Following PRISMA-ScR guidelines, we analyzed literature (2015-2025) from PubMed, Scopus, and other major databases, including English-language rodent studies reporting gut and splenic outcomes. Results: Analysis of 48 studies suggests that gut dysbiosis may alter splenic architecture and immune function mainly via microbial metabolites, particularly short-chain fatty acids. Limited evidence indicates that splenic dysfunction could impair gut barrier integrity. Systemic stressors (e.g., infection or allergy) may reinforce this bidirectional inflammatory loop. Microbiota-targeted therapies have been observed primarily through gut-initiated mechanisms. Vagus nerve-mediated signaling points to a gut-brain-spleen network, though its directional hierarchy remains unresolved. Conclusion: Evidence supports a gut-spleen axis in rodents, with gut-derived microbial metabolites appearing to influence splenic immunity. Support for a reciprocal spleen-to-gut pathway remains limited and emergent, highlighting a research asymmetry. Together, these interactions suggest a partially bidirectional network linking the gut ecosystem to systemic immunity, with additional neural integration extending this framework toward a gut-brain-spleen axis. This integrative model proposes the gut-spleen axis as a potential therapeutic target warranting further investigation in inflammatory, metabolic, and neurological diseases.

Kidney and uropoetic system diseases represent a major social, economic and health burden. This is mainly because early diagnosis of kidney dysfunction is currently unavailable, since the current markers are often reliably increased only after advanced progression of the renal diseases. Recently, circulating nucleosomes, DNA and numerous forms of RNA have been detected in human biological fluids, such as plasma, urine, saliva, and breast milk. Although their biological functions remain mostly unknown, they are attractive as potential biomarkers of various diseases. In urine, many of the circulating nucleic acids originate from the cells of the kidney and the urinary tract making these non-invasive and easily obtained new biomarkers in the nephrology or urology. This review focuses on cell free nucleic acids in urine and its potential in human studies. Although, there are some technical and biological limitations, the urinary circulating nucleic acids hold a great potential as new biomarkers of renal diseases.

Background: Atrial fibrillation is common in patients with structural heart disease who are undergoing cardiac surgery. Surgical CryoMaze has been shown to be an effective treatment in several trials, but success rates have varied considerably, between 47-95%. The sequential hybrid approach, combining surgical CryoMaze followed by radiofrequency catheter ablation, can achieve high freedom from atrial arrhythmias. However, in patients with concomitant surgical atrial fibrillation treatment, data comparing the hybrid approach to CryoMaze alone are lacking. Methods: The SurHyb study was designed as a prospective, open-label, multicentre randomized trial. Patients with non-paroxysmal atrial fibrillation who were scheduled for coronary artery bypass grafting or valve repair/replacement were randomized to either surgical CryoMaze alone or surgical CryoMaze followed by radiofrequency catheter ablation 3 months post-surgery. The primary outcome measure was arrhythmia-free survival without class I or III antiarrhythmic drugs, which has been evaluated using implantable cardiac monitors. Conclusions: This is the first randomized study that compares concomitant surgical CryoMaze alone with the staged hybrid surgical CryoMaze followed by catheter ablation, in patients with non-paroxysmal atrial fibrillation using rigorous rhythm monitoring. The results may contribute to the optimization of the treatment in patients undergoing concomitant CryoMaze for atrial fibrillation.

Ticks are parasites that feed on the blood of humans and animals, using it as their sole source of food. Due to their lifestyle, ticks at each life stage transmit various tick-borne pathogens while feeding on their hosts. Unlike mosquitoes - another important group of pathogen-transmitting arthropods - ticks can feed on the same host for prolonged periods, which underscores the importance of tick mechanisms that inhibit or reduce the host's defence mechanisms and, consequently, allow the transmission of pathogens. This unique tick-host-pathogen triangle requires the involvement of various tick molecules to mediate interactions with both host and pathogen molecules at multiple levels. This review highlights the glycan molecules identified in various tick species that can trigger an immune response and thus primarily affect the interaction with the host. As the enzymes involved in Golgi-mediated glycan maturation differ between ticks, insects, and their vertebrate hosts, these differences contribute to the glycan profiles observed in ticks. These differences in glycan structures influence the interactions ticks have with their hosts and pathogens. On one hand, they may participate in molecular mimicry and mechanisms that lower the host's immune reaction, blood clotting, and other defence mechanisms due to their different structures, but on the other hand they may also trigger the host's defence mechanisms, such as participating in delayed red meat allergy and facilitating the transmission of pathogens. Tick glycobiology remains largely unexplored and deserves more attention, especially considering the potential of glycans and glycoproteins as targets for anti-tick vaccines.

Oxaliplatin-induced toxicity presents a major challenge in cancer management because of its damaging effects on normal tissues, including the reproductive system. Transglutaminase 4 (TG4), a member of the transglutaminase enzyme family, is known for its role in protein cross-linking and cellular stress responses, but its role in chemotherapy-induced reproductive toxicity remains poorly understood. This study examines the impact of oxaliplatin, a platinum-based chemotherapeutic drug, on TG4 expression, enzymatic activity, and testicular toxicity in a rat model following intraperitoneal administration of oxaliplatin (10 mg/kg body weight weekly for six weeks). Biochemical analysis revealed significant hormonal and inflammatory alterations, including elevated serum interleukin-1β (IL-1β) levels, decreased testosterone concentrations, and increased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels. These endocrine disturbances were accompanied by significant upregulation of TG4 expression in oxaliplatin-treated testicular tissue (OXP-TT), as demonstrated by quantitative real-time reverse transcription PCR (qRT-PCR) and immunohistochemical (IHC) analyses. Immunofluorescence (IF) further confirmed enhanced TG4 localization within both interstitial and seminiferous tubular regions. In addition, expression of the pro-inflammatory cytokines IL-6 and TNF was significantly increased. A marked elevation in total transglutaminase enzymatic activity was also detected in oxaliplatin-treated tissues. Collectively, these hormonal, inflammatory, and structural alterations occurred concurrently with increased TG4 expression and transglutaminase activity, suggesting that TG4 participates in the testicular response to oxaliplatin-induced stress. These findings indicate that TG4 is associated with chemotherapy-related reproductive toxicity and may represent a stress-responsive indicator of testicular injury. Further studies are required to determine whether TG4 plays a protective or pathogenic role in oxaliplatin-induced testicular damage and to evaluate its potential relevance in preserving fertility during platinum-based chemotherapy.

Melanins are polymorphous and multifunctional biopolymers with a relatively high concentration of free radicals. EPR spectroscopy was used to study o-semiquinone free radicals in model eumelanins synthesized from 3,4-dihydroxyphenylalanine (DOPA) and tyrosine in the presence of tyrosinase, and melanins isolated from A-375 and G-361 human melanoma malignum cells exposed to two compounds: 5,7-dimethoxycoumarin (DMC) and valproic acid (VPA). Changes were determined in the concentrations of free radicals in the individual melanins from tumour cells treated with DMC and VPA. A strong decrease in the concentrations of free radicals characterizes melanins isolated from tumour cells treated together with DMC and VPA. Slow spin-lattice relaxation processes were noted in the melanins tested with homogeneous broadened EPR spectra. The EPR technique may be useful not only for the elucidation of free radicals in melanins from A-375 and G-361 cells treated with VPA and DMC but it could also be applied to establish the relationship between melanin type and the malignancy of melanoma malignum.

The study focused on the changes in C-peptide, glycemia, insulin concentration, and insulin resistance according to LDL-cholesterol concentration ranges. The metabolic profile of individuals in the Czech Republic (n = 1840) was classified by quartiles of LDL-cholesterol into four groups with the following ranges: 0.46-2.45 (n = 445), 2.46-3.00 (n = 474), 3.01-3.59 (n = 459), and 3.60-7.18 mmol/l (n = 462). The level of glucose, C-peptide, insulin, and area of parameters during OGTT and HOMA IR were compared with a relevant LDL-cholesterol range. The evaluation involved correlations between LDL-cholesterol and the above parameters, F-test and t-test. Generally, mean values of glucose homeostasis-related parameters were higher with increasing LDL-cholesterol levels, except for mean HOMA IR values which rapidly increased (2.7-3.4) between LDL-cholesterol ranges of 3.00-3.59 and 3.60-7.18 mmol/l. Glucose, C-peptide, insulin concentrations, and the area of parameters reached greater changes especially after glucose load during OGTT (p ≤ 0.001). Considerable changes were already observed for the above parameters between groups with LDL-cholesterol ranges of 2.46-3.00 and 3.01-3.59 mmol/l. HOMA IR increased with higher LDL-cholesterol concentrations, but the differences in mean values were not statistically significant. Most important differences appeared in glucose metabolism at LDL-cholesterol concentrations of 3.60-7.18 mmol/l in comparison to LDL-cholesterol lower ranges. In particular, the areas of C-peptide, glucose, and insulin ranges showed statistically significant differences between all groups with growing LDL-cholesterol ranges. The variances of HOMA IR statistically differed between groups created according to LDL-cholesterol concentrations ranges.

Acute lymphoblastic leukemia (ALL) is the most common childhood hematological malignancy, but it also affects adult patients with worse prognosis and outcomes. Leukemic cells benefit from protective mechanisms, which are mediated by intercellular signaling molecules - cytokines. Through these signals, cytokines modulate the biology of leukemic cells and their surroundings, enhancing the proliferation, survival, and chemoresistance of the disease. This ultimately leads to disease progression, refractoriness, and relapse, decreasing the chances of curability and overall survival of the patients. Targeting and modulating these pathological processes without affecting the healthy physiology is desirable, offering more possibilities for the treatment of ALL patients, which still remains unsatisfactory in certain cases. In this review, we comprehensively analyze the existing literature and ongoing trials regarding the role of chemokines and interleukins in the biology of ALL. Focusing on the functional pathways, genetic background, and critical checkpoints, we constructed a summary of molecules that are promising for prognostic stratification and mainly therapeutic use. Targeted therapy, including chemokine and interleukin pathways, is a new and promising approach to the treatment of cancer. With the expansion of our knowledge, we are able to uncover a spectrum of new potential checkpoints in order to modulate the disease biology. Several cytokine-related targets are advancing toward clinical application, offering the hope of higher disease response rates to treatment.

Background: HCC is a prevalent malignant tumor globally with high mortality. MiR-500a-3p plays critical roles in tumorigenesis and tumor progression. Methods: To evaluate miR-500a-3p's role in HCC, we first analyzed its expression and prognostic value via qRT-PCR and TCGA (Kaplan-Meier analysis). We then performed extensive in vitro functional studies after cell transfection (mimics, anti-miR, SOCS2 OE), measuring proliferation, migration, invasion, glycolytic parameters (glucose consumption, lactate, ECAR, ATP), and apoptosis. A target relationship with SOCS2 was predicted bioinformatically and confirmed by dual-luciferase assay. Using the JAK2/STAT5 signaling pathway inhibitor Fedratinib, the activator Erythropoietin, and transfection with si-STAT5 and oe-STAT5, the molecular mechanism of miR-500a-3p in HCC was investigated. In vivo experiments established tumor-bearing mouse models to evaluate the effect of miR-500a-3p on tumor growth. Results: miR-500a-3p was significantly upregulated in HCC tissues and cells, and was associated with poor patient prognosis. The overexpression of miR-500a-3p promotes the malignant progression of HCC cells. Mechanistically, miR-500a-3p directly targeted and negatively regulated SOCS2 expression. SOCS2 expression was suppressed in HCC, with its expression abrogating miR-500a-3p-mediated oncogenicity. miR-500a-3p activated the JAK2/STAT5 pathway by inhibiting SOCS2, thereby regulating the malignant biological behaviors of HCC cells. Both SOCS2 overexpression and JAK2 inhibitor treatment could reverse the activation of the JAK2/STAT5 axis and downstream effects induced by miR-500a-3p. MiR-500a-3p promoted tumor growth in tumor-bearing mice, accompanied by SOCS2 downregulation and JAK2/STAT5 pathway activation. Conclusion: This study reveals that miR-500a-3p promotes proliferation and glycolysis while inhibiting apoptosis of HCC cells by negatively regulating SOCS2 and activating the JAK2/STAT5 pathway.

The numerous challenges and detrimental effects connected with the treatment of peptic ulcers in the world today calls for alternative attention. Ethnomedicinally, Dialium guineense pulp (DAGP) has numerous pharmacological activities. This study investigated the anti-ulcer activities of Dialium guineense pulp on gastric mucosa injury induced with aspirin in albino Wistar rats. DAGP extract was orally administered at doses of 250, 500 and 1000 mg/kg bw (mg per kg of the body weight) per day for 3 or 7 days followed by 400 mg/kg bw oral aspirin administration. Ulcer indices were determined, followed by a biochemical estimation of antioxidant enzymes using gastric mucosal tissue from the stomach. Student's t-test was used to compare significant differences among groups of animals at P ≤ 0.05. The results showed that Dialium guineense pulp caused a significant decrease (P ≤ 0.05) in the ulcer index in aspirin induced rats. This decrease in ulcer index is dose dependent and 1000 mg/kg bw per day caused the highest decrease in 7 days. The results showed a significant increase (P ≤ 0.05) in lipid peroxidation and a decrease (P ≤ 0.05) in antioxidant enzymes activities in the aspirin-induced ulcerated rats. Oral administration of DAGP increased antioxidant enzymes activities and decreased injury in the gastric mucosa in ulcer induced rats. Therefore, this study showed that DAGP exhibited anti-ulcer potential and that the gastrointestinal protection may be through the scavenging action of free radicals by its constituent antioxidants. Thus, Dialium guineense pulp has ameliorative medicinal potential for the curing of gastric disorders.

Birth is an event that exposes the newborn baby to a high concentration of free radicals (reactive oxygen species (ROS)/reactive nitrogen species (RNS)), which can contribute to several diseases. The balanced equilibrium between ROS/RNS and the antioxidant system of the newborn is a key factor in preventing a plethora of diseases. The antioxidant system involves endogenous and exogenous molecules, from vitamins (A, E, C) to enzymes (glutathione peroxidase, superoxide dismutase), metals (copper, zinc, and selenium) and other molecules (coenzyme Q₁₀, melatonin) that can act in a synergistic manner to deactivate free radicals. A competent antioxidant system of the baby is strongly dependent on the intake of free radical deactivating molecules from feeding, either maternal or formula milk, with several studies pointing that breast milk has more powerful antioxidant effects on lowering the infant's oxidative status. An improved understanding of the antioxidant molecules, their mechanism of action, and the relationships between them, are key factors to comprehend all the potential benefits of human breastfeeding in this matter. The purpose of this review is to describe different research efforts and methodologies of evaluation of TAS in human milk, and to evaluate and summarize the contribution of different antioxidant molecules.

A substantial threat to worldwide health, the proliferation of antibiotic-resistant bacteria compels researchers to seek innovative antibacterial substances. This systematic review assesses the role of nanoparticles, particularly Calcium oxide and Silicon oxide nanoparticles, in infection control. The article examines the mechanisms by which these nanoparticles act against various bacteria and evaluates their potential as novel agents in infection control strategies. A systematic literature search from 2015 to 2024 encompassing Web of Science, PubMed, Wiley, Science Direct, and Google Scholar, yielded 70 publications meeting the review criteria. This comprehensive methodology provides a thorough understanding of the capabilities and limitations of Calcium oxide and Silicon oxide nanoparticles as antibacterial agents. The review aims to build a solid foundation for the utilization of nanoparticles in addressing the obstacles presented by antibiotic resistance by combining data from various investigations. Additionally, it aims to explore the safety and environmental implications associated with their use in clinical and environmental settings, providing a comprehensive analysis that may contribute to future studies and real-world applications in the field of antimicrobial technology.

The fundamental aspect of breast cancer metastasis is the infiltration of malignant cells, which can be blocked by propofol, a widely utilized anesthetic in clinical settings, as recent studies reporting. However, research utilizing three-dimensional invasion models in vitro has not been documented. This study created a microfluidic chip model utilizing type I collagen (Col1), integrating delayed dynamic imaging and several fluorescence labeling approaches to objectively assess the inhibitory effect of propofol on breast cancer cell MDA-MB-231 invasion. Research indicates that MDA-MB-231 cells demonstrate collective invasion behavior, with their invasive capacity reliant on the degradation of the extracellular matrix (ECM) facilitated by matrix metalloproteinases (MMPs): both the invasion distance and cell count diminish as matrix hardness (collagen concentration 1-2.5 mg/ml) increases, while they augment with extended culture duration (1-5 days). Subsequent research has demonstrated that propofol (12.5-50 μg/ml) can reduce both the invasion distance and quantity of MDA-MB-231 cells in a dose-dependent manner, potentially linked to the down-regulation of MMP-2/MMP-9 and the up-regulation of tissue inhibitor of metalloproteinase-1 (TIMP-1) expression. This paper presents novel experimental evidence that propofol inhibits the invasion of breast cancer cells, and establishes a straightforward and quantitative medication evaluation platform, offering a methodological reference for the screening and mechanistic investigation of tumor microenvironment regulators.

Aim: This study aimed to investigate the phenolic composition, antioxidant capacity, and toxicity of aqueous extracts of Calamintha nepeta L. leaves and their potential vasorelaxant effects. Methods: Aqueous extracts of Calamintha nepeta L. were prepared by three extraction methods: decoction, infusion, and maceration. The total phenolic contents of the extracts and their antioxidant properties were investigated. The toxicity was evaluated by Artemia salina lethality bioassay. The decoction extract was analyzed by HPLC for its chemical profile and was also used to evaluate the vasorelaxant effect on thoracic aortic rings isolated from healthy Sprague Dawley rats. Pre-contraction was induced by phenylephrine, followed by cumulative doses of the extract (0.001 up to 250 µg/ml). Results: Aqueous extracts of Calamintha nepeta L. showed noticeable radical scavenging and chelating activities. However, the decoction extract exhibited the most powerful antioxidant capacity. No toxicity was recorded for the extracts obtained by decoction and infusion. Caffeic acid, quercetin, and rosmarinic acid were the main identified compounds. Notably, the aqueous extract obtained by decoction induced significant relaxation in endothelium-intact aortic rings at lower concentrations, and at higher concentrations in denuded aortic rings. Conclusion: This study reveals that Calamintha nepeta L. extracted with a decoction method possesses potent antioxidant capacity and has an endothelium-dependent vasorelaxant effect.

Introduction: ORBEYE^TM exoscope offers superior visualization with clearer imaging compared to standard methods and supports narrow band imaging (NBI). ORBEYE^TM provides better visualization of tissue structures, thus increasing the accuracy of the surgical procedure. The systematic use of ORBEYE^TM in transoral exoscopic laryngeal surgery (TOLES) is rarely documented. This study evaluates the sensitivity and specificity of TOLES using ORBEYE^TM with white light and NBI modalities. Methods: Between 8/2021 and 8/2024, 84 patients underwent TOLES using ORBEYE^TM with white light and NBI modes. All surgeries were performed in a specialized setting with consistent preoperative and intraoperative imaging protocols. Results: TOLES using ORBEYE^TM was successfully performed in all 84 patients. A statistically significant dependence (p < 0.001) was observed between preoperative/perioperative (TOLES) findings and definitive histology for both white light and NBI modalities. ORBEYE^TM facilitated detailed imaging of tissue structures and allowed targeted biopsies. Conclusion: TOLES with perioperative NBI/white light endoscopy achieved a high correlation between pre-histopathological diagnoses and final histopathological results. ORBEYE^TM exoscope provides three-dimensional 4K resolution, superior imaging, and improved ergonomics for the surgeon, reducing workload and increasing efficiency. It delivered more efficient surgical team collaboration and experience sharing. The integration of NBI into the TOLES system facilitated accurate navigation and targeting of the biopsy, helping to establish correct definitive diagnosis. TOLES showed more accurate scoring of perioperative NBI findings.

Background: The antidiabetic drug metformin has been repeatedly detected in surface waters worldwide. This study investigates the effects of the environmentally relevant concentration of metformin on a non-target aquatic organism - a freshwater crustacean, Daphnia magna, with an emphasis on the stress response of daphnids and the long-term effects on their consecutive generations. Methods: The chronic toxicity test and the consecutive generations test were inspired by the OECD method. The total antioxidant capacity (Trolox equivalent - TEAC), superoxide dismutase (SOD) activity, and catalase (CAT) activity were related to the protein content in the tested daphnids. Results: Elevated antioxidant activities were revealed in daphnids exposed to metformin in comparison to the control group (1.9 × for TEAC, 1.7 × for SOD; 1.3 × for CAT). Furthermore, diminished body sizes and malformations in the digestive system, spine and carapace were detected in newborn juveniles in the second and third generations exposed to metformin. Conclusion: Long-term exposure to metformin in environmentally relevant concentrations led to a significant detrimental reaction in aquatic crustaceans.

The development of new treatments for inflammation continues to be of high interest, since long-acting effect is critical for patients. We investigated whether meloxicam-loaded lipid-core nanocapsules (M-NC) have an anti-inflammatory action superior to a free drug (M-F) on a mouse pleurisy model, by analyzing the time-course of leukocytes migration in the pleural fluid. Male adult Swiss mice were divided into six groups for each time (24; 48 and 72 h) and were pretreated with blank nanocapsules (17 ml/kg) or M-NC (5 mg/kg) or free meloxicam (M-F) (5 mg/kg). After pretreatments, mice received saline (0.9%) or carrageenan (Cg) (1%) into pleural cavity. Four hours after Cg or saline administration, animals were killed, pleural cavity was washed and pleural fluid was collected for the determination of total leukocytes. Cytokines levels, differential leukocyte count and α-1-acid glycoprotein (AGP) levels were determined only at 48 h of pretreatment, which had effect on total leukocyte count. M-NC were effective against the increase in total and differential leukocyte counts and pleural exudate caused by Cg, while M-F had no effect. M-NC had superior effect to M-F against the increase in cytokines and AGP levels induced by Cg. In summary, M-NC had a superior anti-inflammatory effect to free drug in Cg-induced pleurisy, supporting the idea that the inflammatory process in tissues facilitates the vectorization of polymeric nanoparticles.

Helicobacter pylori (H. pylori), which is found in the stomach of approximately 50% of humans, remains there for almost the entire lifetime of the infected individual, leading to various gastrointestinal tract-associated disorders following full-blown infection. Due to the emergence of antibiotic resistance, recurrence and high cost of therapy, most antibiotic-based treatment strategies are not very effective in eradicating H. pylori infections. The quest for an alternative treatment free of these inconveniences is currently in demand. One of the important alternatives is propolis, produced by the honeybee Apis mellifera, which has been used to treat different diseases since it possesses a wide range of biochemical properties. Propolis has been reported as a useful therapeutic regimen against H. pylori, which is an important cause of gastric inflammation, peptic ulcer, gastric cancer, and lymphomas of mucosa-associated lymphoid tissues. Apart from propolis, various active compounds of other natural products have also been confirmed to be effective. This review compiles the scientific evidence of the role of propolis and other natural products against H. pylori-associated gastrointestinal tract-related health complexities by acing as an anti-angiogenic, anti-inflammatory, and antioxidant factor as well as via modulation of enzymatic activities.

To investigate the association between inflammatory biomarkers and overt hypothyroidism (OH). We measured inflammatory cytokines, interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) as well as cell-free DNA (cf-DNA) levels in 40 OH patients and 40 healthy controls. Total cholesterol, high and low density lipoprotein subfractions, triglyceride, fibrinogen, and D-dimer were recorded. Increased inflammatory profile was evidenced through significant elevations in the concentrations of all cytokines and cf-DNA levels in the OH group. Lipids and prothrombotic markers were also increased in hypothyroid subjects. A significant association between the inflammatory cytokines and lipid profile was observed. A multivariate analysis showed that this result was independent of the sex, age and BMI status of the subjects. Hypothyroidism is associated with proinflammatory state. Lipid abnormalities have a stronger influence on inflammation, increasing cardiovascular risk and atherosclerosis development in hypothyroidism.

Background and objectives: We aimed to determine the effects of vanillic acid (VA) on fracture healing radiologically, histologically, immunohistochemically, and biomechanically using a rat femur open fracture injury model. Methods: 32 male Wistar-Albino rats were used and divided into two groups: the study group (VA) and the control group. From the time they were operated on until they were sacrificed, the rats in the study group were given 100 mg/kg/day VA by oral gavage. After sacrification, the femurs were analyzed. Results: It was observed that the Huo histological scoring was significantly higher in the VA group (p = 0.001), and the ratio of the amount of callus tissue compared to intact bone tissue was significantly higher. While no significant difference was observed in immunohistochemical H-scores in ColI antibody staining (p = 1.000), a borderline significant difference in favor of VA was observed in ColIII antibody staining (p = 0.078). In biomechanical analysis, failure load (N), total energy (J), maximum stress (MPa), and stiffness (N/mm) measurements were significantly higher in the VA group (p = 0.040, p = 0.021, p = 0.015, and p = 0.035, respectively). Conclusion: It has been observed that VA, with its antioxidative properties, increases fracture healing in rats, in which an open fracture model was created. We are hopeful that such an antioxidant, which is common in nature, will increase fracture healing. Since this study is the first to examine the effect of VA on fracture healing, further studies are needed.

Myo-inositol (MI), present in a variety of foods, is essential in several important processes of cell physiology. In this study, we explored the protective effects of MI against hyperglycemia and dyslipidemia in db/db mice, a typical animal model of type 2 diabetes mellitus (T2DM). MI supplement effectively suppressed the high plasma glucose and insulin levels and markedly relieved the insulin resistance (IR) in the db/db mice, comparable to metformin's effects. In MIN6 pancreatic β cells, MI also restrained the upsurge of insulin secretion stimulated by high-concentration glucose but had no impact on the promoted cell proliferation. Moreover, MI abated the enhanced plasma triglyceride and total cholesterol levels in the db/db mice. Notably, the lipid droplet formation of mesenchymal stem cells (MSCs) from db/db mice was significantly diminished after the treatment of MI, indicating that MI could effectively inhibit the differentiation of db/db mouse MSCs into adipocytes. However, MI regretfully failed to control obesity in db/db mice. This work proved that MI significantly helped db/db mice's metabolic disorders, indicating that MI has potential as an effective adjunctive treatment for hyperglycemia and dyslipidemia in T2DM patients.

Spisulosine (1-deoxysphinganine) is a sphingoid amino alcohol isolated from the sea clams that showed potent antiproliferative activity against a broad spectrum of solid tumors but failed in clinical trials due to neurotoxicity. However, its structural similarity to other bioactive sphingoids, interesting mode of action, and appreciable potency against cancer cells make it a suitable lead for future anticancer drug development. The present study was conducted to elucidate mechanisms of the antiproliferative/cytotoxic effects of newly synthesized spisulosine analog homospisulosine (KP7). The evaluation was performed on cervical carcinoma cells, representing an in vitro model of one of the most common cancer types and a significant worldwide cause of women's cancer mortality. Treatment with homospisulosine (2.0 μM) for 24, 48, and 72 h significantly inhibited the growth of HeLa cells in vitro and induced apoptosis detectable by DNA fragmentation, externalization of phosphatidylserine, dissipation of mitochondrial membrane potential, activation of caspase-3 and cleavage of PARP. In addition, treating HeLa cells with spisulosine increased p27 and Bcl-2 on protein levels and phosphorylation of Bcl-2 on Ser70 residue. These results support the potential for spisulosine analogs represented here by homospisulosine for future therapeutic development.

Cholesterol-lowering drugs, antidiabetics, antiarrhythmics, antidepressants, and antibiotics belong to the most prescribed drugs worldwide. Because of the manufacture, excretion, and improper disposal of leftover drugs, the drugs enter waste waters and, subsequently, surface waters. They have been detected in surface waters all over the world, from concentrations of ng/l to concentrations several orders of magnitude higher. Since pharmaceuticals are designed to be both biologically and chemically stable, photochemical degradation by sun radiation represents a way of transformation in the natural environment. This review provides a survey of how selected drugs of the above-mentioned classes affect aquatic organisms of different trophic level. The emphasis is on the harmful effects of phototransformation products, an area of scientific investigation that has only attracted attention in the past few years, revealing the surprising fact that products of photochemical degradation might be even more toxic to aquatic organisms than the parent drugs.

Purpose: The aim of this study was to investigate whether luteoloside, a flavonoid, could protect human dental pulp cells (HDPCs) against inflammation and oxidative stress induced by methylglyoxal (MGO), one of the advanced glycated end products (AGE) substances. Methods: HDPCs were stimulated with MGO and treated with luteoloside. MTT assay was used to determine cell viability. Protein expression was measured via western blotting. Reactive oxygen species (ROS) were measured with a Muse Cell Analyzer. Alkaline phosphatase activity (ALP) and Alizarin red staining were used for mineralization assay. Results: Luteoloside down-regulated the expression of inflammatory molecules such as ICAM-1, VCAM-1, TNF-α, IL-1β, MMP-2, MMP-9, and COX-2 in MGO-induced HDPCs without showing any cytotoxicity. It attenuated ROS formation and enhanced osteogenic differentiation such as ALP activity and Alizarin red staining in MGO-induced HDPCs. Overall, luteoloside showed protective actions against inflammation and oxidative stress in HDPCs induced by MGO through its anti-inflammatory, anti-oxidative, and osteogenic activities by down-regulating p-JNK in the MAPK pathway. Conclusion: These results suggest that luteoloside might be a potential adjunctive therapeutic agent for treating pulpal pathological conditions in patients with diabetes mellitus.