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.
PURPOSE:To report on a 5-year follow-up of Implantable Collamer Lenses (ICL) implantation and compare it to previously published iris-fixated phakic intraocular lenses (IF pIOLs). METHODS:We describe the refractive results and adverse events of 30 eyes in 18 patients with high myopia, keratoconus, or status post-keratoplasty (PKP), at one, two and five years after surgery. RESULTS:Efficacy and safety index were 0.94 and 1.04, respectively, at 5 years after surgery. Intraocular pressure (IOP) was significantly higher postoperatively (p = 0.005). The endothelial cell loss (EC loss) caused by the ICL implantation was found to be 3.82%, 5.03%, and 11.41%, at one-, two-, and five-years post-surgery. During a 5-year follow-up, 92% of eyes lost a higher percentage of endothelial cells (EC) than the expected physiological loss. Among eyes with >25% EC loss, all affected eyes at 2 years, and 80% at 5 years, had either keratoconus or history of keratoplasty prior to ICL implantation. Postoperative EC loss positively correlated with preoperative keratometry and negatively with preoperative pachymetry. Significant inverse relationship was found between baseline and postoperative anterior chamber angle (ACA) and EC loss. Postoperative vault (388 ± 159 μm) showed a negative correlation with endothelial cell density (ECD) in 5-year follow-up. There was no cataract formation at 5 years postoperatively. CONCLUSION:Compared to the IF pIOLs, the V4c ICLs have similar frequency of postoperative cataract formation but appear to be safer for the endothelium. Therefore, they are likely more suitable for keratoconus and PKP patients. However, the risk of long term IOP elevation seems to be higher.
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.
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.
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.
Immune checkpoints are one of the mechanisms that maintain the balance between immunotolerance and immunopathology. These mechanisms are often exploited by tumour cells. Thanks to extensive global testing of anticancer drugs, a revolutionary cancer therapy based on immune checkpoint inhibitors (ICIs) has been developed. Some pathogens exploit regulatory checkpoint interactions, contributing to the establishment of hidden, long-term, or persistent infections in which the host is unable to eliminate the pathogen. However, a structured overview of immune checkpoint involvement in bacterial infections remains underrepresented in the current scientific literature. We conducted a literature review focusing on the documented role of selected immune checkpoints (specifically PD-1, PD-L1, TIM-3, LAG-3, CTLA-4, and TIGIT) during infections of humans and animals with clinically relevant bacterial pathogens from the Actinobacteria, Chlamydiae, Firmicutes, Proteobacteria, and Spirochaetae phyla. The current state of knowledge suggests that applied research into immune checkpoints and the controlled use of ICIs has great potential to improve the diagnosis, treatment, and prognosis of serious human bacterial infections.
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.
A method for detecting epileptic spikes in EEG recordings that leverages additional EMG channels to identify and remove muscle artifacts is presented. Unlike conventional approaches, our method models the uneven propagation of muscle artifacts by applying a filter bank and linear regression to clean the EEG signal. Spike detection is then performed using template matching with user-defined parameters, such as amplitude and duration, designed for neurophysiological interpretability. To validate our approach, we developed a dedicated database comprising EEG and EMG recordings from 20 participants. Artificial triangular spikes were added to EEG segments contaminated with muscle artifacts, creating numerous examples of spikes masked by artifacts. This dataset enabled a systematic evaluation of both preprocessing and spike detection techniques. Our method achieved a sensitivity of 0.88, specificity of 1.00, and precision of 0.79 in the detection of simulated spikes. Further testing on real EEG data with interictal spikes and added muscle artifacts yielded a sensitivity of 0.83, specificity of 0.99, and precision of 0.71, demonstrating robust performance even under challenging conditions. These results indicate that incorporating EMG channels to account for muscle activity substantially improves the effectiveness of EEG signal analysis. The proposed approach facilitates reliable detection of epileptic spikes, even when masked by muscle artifacts, and allows neurophysiologists to tailor detection criteria to specific amplitude and temporal features.
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.
Hepatitis B virus (HBV)-related liver disease is an inflammatory-associated disease, with diverse clinical phenotypes ranging from asymptomatic HBV carriers to hepatocellular carcinoma. Interleukin-37 (IL-37), a cytokine that effectively inhibits innate and adaptive immunity, has powerful anti-inflammatory and anti-tumor effects. Several single nucleotide polymorphisms (SNPs) in the IL37 gene are genetic predictive risk factors for HBV infection and HBV-mediated liver disease progression. However, different ethnic groups may have different allele frequencies and linkage disequilibrium structures. The effect of SNPs in IL37 on HBV infection and its relationship with different clinical outcomes have not been clarified among the Han people in southern China. Based on in silico functional prediction and previously reported in the literature to be potentially associated with diseases, we screened seven potentially functional SNPs (rs3811046, rs3811047, rs2723176, rs2723186, rs4611652, rs4392270, and rs4241122) located in the IL37 genomic region and 3-kb upstream and downstream of the gene body. 1,582 subjects were included in the study, including 747 patients with HBV-related liver disease, 405 patients who cleared HBV, and 430 healthy controls. The seven SNPs were genotyped using the SNaPshot SNP assay, and co-dominant, dominant, and recessive models were used to explore the association of each SNP with HBV infection and clinical outcomes after HBV infection. The rs4241122 demonstrated a significant association with both HBV infection and its clinical outcomes, with the GG genotype identified as an independent protective factor for spontaneous clearance of HBV. The rs2723186 and rs4392270 were also significantly associated with HBV clearance under specific genetic models. Furthermore, rs3811046 and rs3811047 were correlated with the progression of liver abnormalities following HBV infection. Our data suggests that SNPs at the IL37 locus are associated with susceptibility to HBV infection and clinical outcomes after HBV infection.
Central nervous system (CNS) inflammation occurs in cognitive dysfunction, but the underlying mechanisms remain unclear. The newly discovered pattern of cell death in recent years is called pyroptosis, which is distinguished from apoptosis and necrosis, and is mainly dependent on caspase-1 mediated inflammatory response. Stem-derived exosomes have immunomodulatory and immunosuppressive effects. In the present study, we aimed to investigate the exosomes (Ex) secreted by lipopolysaccharide (LPS)-stimulated macrophages (LPS-Ex) to attenuate the neuroinflammatory response caused by systemic LPS stimulation by attenuating pyroptosis. We studied lipopolysaccharide (LPS)-induced cognitive impairment and neuroinflammation in C57BL/6 mice by behavioral testing, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), Western blotting, and other methods. We found that LPS-Ex can reduce the level of inflammatory factors, down-regulate the pyroptosis pathway and the inflammatory pathway of NF-κB, and improve the inflammatory response of neurological function in mice. The conclusion is that LPS-Ex relieves neuroinflammation by reducing pyroptosis. It can be used as a novel therapeutic strategy for neuroprotection and functional recovery in the onset of central nervous system inflammation.
The shoulder's dynamic function is largely influenced by scapulohumeral rhythm (SHR), a coordinated movement of the scapula and humerus that facilitates a safe range of motion. While SHR has been described and quantified in terms of shoulder kinematics, its specific contribution to glenohumeral joint stability. This study aims to estimate the impact of SHR on glenohumeral stability using a biomechanical model. A five-segment musculoskeletal model based on the work of Wu et al. (2016) was implemented in OpenSim. Three SHR patterns and two loading scenarios were evaluated: a fixed scapula, a humeral-to-scapular motion ratio, and an experimentally measured SHR with free abduction or abduction while holding a 2 kg weight in the hand. Muscle forces and glenohumeral stability ratios were calculated using static optimization, and the model predictions were compared to electromyography and in vivo joint force data. While glenohumeral contact forces showed minimal variation across different SHR conditions, the stability ratio analysis revealed that the absence of SHR significantly increased the risk of joint instability. In scenarios without SHR, even small shoulder elevations resulted in overloading of the superior glenoid. The addition of weight further destabilized the joint, while substantially increasing glenohumeral force. SHR does not reduce the overall glenohumeral load but plays a critical role in maintaining glenohumeral stability, particularly during early phases of shoulder elevation and when holding additional weight. These findings highlight the importance of scapular kinematics in shoulder joint function and may have implications for managing shoulder pathologies such as rotator cuff tears and impingement, where scapular motion is often compromised.
pH monitoring in biological fluids plays a critical role in clinical diagnostics and therapeutic management. This study presents a novel solid-contact pH electrode fabricated using a direct-printed (DP) graphite (Gr) electrode on a flexible substrate, followed by an electropolymerized hydrophobic polyazulene (pAz) transducing layer, and an ion-selective membrane (ISM). The pH electrode was paired with a miniaturized solid-state Ag/AgCl reference electrode incorporating a photopolymerized PVA-KCl matrix. The miniaturized reference electrode exhibited excellent potential stability (+/- 2.5 mV across pH 2-11), and minimal signal drift (10 mu V/h). The miniaturized pH electrode exhibited a sensitivity of 55.7 mV/dec, with a rapid response time of 6 s (vs. OrionTM ROSS UltraTM reference electrode) or 42 s (vs. miniaturized solid-state reference electrode) and a linear response over the pH range of 2-10. The pH electrode demonstrated excellent analytical performance in diverse biological fluids, including urine, serum, saliva, and surgical drain fluid, closely matching the performance of a laboratory-grade combined glass pH electrode. These results underscore the potential of the proposed platform as a reliable and technologically scalable tool for real-time pH assessment in biomedical applications.
Human postural stability represents a complex, nonlinear system influenced by a range of biomechanical and environmental factors. The trajectories of the center of pressure (CoP) serve as key indicators of this system’s underlying dynamics and are increasingly being analyzed using nonlinear methods. However, the impact of surface-induced instability during gait remains underexplored. This study aimed to analyze CoP behavior during gait on stable (dry) and unstable (slippery) surfaces by testing three hypotheses: (1) task-induced instability is associated with an increase in CoP complexity; (2) individual variability amplifies dynamic fluctuations under unstable conditions; and (3) repeated exposure to the task attenuates this complexity. Twenty healthy young males completed each walking task three times. CoP dynamics were quantified using nonlinear analyses, including phase-space reconstruction (embedding dimension and time lag) and correlation dimension (CD).Complexity metrics, specifically the optimal embedding dimension and CD, were significantly elevated during the slippery surface condition, clearly distinguishing between the two task environments (p < 0.001, classification accuracy > 90 %). The greater variability in features observed under the slippery condition suggested broader dynamic adaptations to instability. Additionally, the reduction in CD across repeated trials indicated a moderating effect of prior exposure.The findings support all three hypotheses, demonstrating the effectiveness of CoP-based nonlinear measures in capturing adaptive postural responses to changing stability demands. This study contributes a novel multi-trial nonlinear analysis approach for evaluating dynamic postural control under environmental challenges.
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.
The use of natural products in cosmetics and pharmacy has risen dramatically in recent years, leading to the overexploitation of flora and fauna worldwide and threatening the environmental sustainability. Microbe-derived components could help to solve the problem due to their independently controllable cultural property. To investigate the potential of microfungi for producing potential novel cosmeceuticals, cerevisterol (1), aloesol (2), 3β,5α,9α-trihydroxyergosta-7,22-diene-6-one (3), and ergosterol peroxide (4) were isolated from the halotolerant fungal strains Penicillium brefeldianum CL6 and Talaromyces sp. S3-Rt-N3. They were then tested for biological properties, including anti-microbial, tyrosinase inhibitory, and wound healing activities. The results revealed the wound-healing potentials of two fungal compounds - (1) and (2) - in terms of cell proliferation promotion in NIH-3T3 murine fibroblasts, and the tyrosinase inhibitory potential of fungal compounds (1), (3), and (4) in the substrates L-tyrosine and L-3,4-dihydroxyphenylalanine (L-DOPA). Interestingly, compound (1) exhibited antimicrobial activity against acne-causing bacterium Propionibacterium acnes. These results have revealed new prospects for the application of microorganisms-derived compounds, especially in the cosmetics industry.
INTRODUCTION:The human nasal cavity and paranasal sinuses host a complex and dynamic microbiome which has a crucial role in mucosal immunity. A comprehensive profile of the healthy sinonasal microbiome remains limited. The purpose of our study was to characterize the healthy sinonasal microbiome in adults using 16S rRNA long-read sequencing to enable species-level resolution, and to assess its associations with demographical and clinical factors such as smoking, allergy history, and olfactory function. STUDY DESIGN:We performed a prospective, single-centre study analysing middle meatus samples from 27 healthy individuals undergoing septoplasty in the age range from 21 to 57 years, excluding those with antibiotic and corticosteroid use and those with signs of acute or chronic rhinosinusitis. RESULTS:A high interindividual variability in the composition of healthy sinonasal microbiome was observed. At the phylum level, it was dominated by Firmicutes (48.96%), Actinobacteria (34.83%), and Proteobacteria (13.85%), while Firmicutes and Actinobacteria were consistently present in all samples. At the genus level, Staphylococcus spp. (32.32%), Cutibacterium (28.04%), and Corynebacterium (4.66%) were most abundant. We observed trend level correlations between phyla and some clinical factors (e.g., smoking and olfactory dysfunction) and selected phyla. However, none remained significant after false discovery rate (FDR) correction across taxa. CONCLUSION:The study proposes Staphylococcus spp., Corynebacterium spp., and Cutibacterium spp. to be a core taxa in the healthy sinonasal microbiome. Amid the interindividual diversity in our cohort, there was evidence of a stable core microbiome potentially influenced by environmental and host factors. Our findings suggest a baseline reference for distinguishing a dysbiosis in upper respiratory disease.
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.
INTRODUCTION:Tonsil-related procedures are considered fundamental and effective in the surgical treatment of obstructive sleep apnea (OSA). The range of techniques includes intratonsillar approaches, such as tonsillotomy (TT), as well as extracapsular procedures, such as tonsillectomy (TE) and uvulopalatopharyngoplasty (UPPP). Patients undergoing these procedures span all age groups, from children to seniors. METHODS:This multicentric retrospective study, conducted between 2014 and 2018, analysed data from 3,498 patients who underwent bilateral TT, TE, or UPPP for OSA or ronchopathy. The cohort included 2,221 men (63.49%) and 1,277 women (36.51%). Of these, 2,808 patients (80.27%) underwent TT, 226 (6.46%) underwent TE, and 464 (13.26%) underwent UPPP. RESULTS:Late postoperative haemorrhage (LPOH) occurrence was significantly associated with the type of surgery (p < 0.0001) and the hospital where the procedure was performed (p < 0.0001). The incidence of LPOH in the TT group ranged from 0% to 5.88% across hospitals (p = 0.0068); whereas in the TE and UPPP groups, rates ranged from 0% to 33.33% (p = 0.0413 and p = 0.0409, respectively). The occurrence of repetitive bleeding was not influenced by treatment choice (readmission vs. outpatient care, observation vs. surgical revision, general vs. local anaesthesia). The severity of bleeding in all three groups was not affected by age and gender. The use of anticoagulants negatively impacted LPOH severity (p = 0.0166) in the UPPP group. No deaths occurred in our sample; however, three cases of severe postoperative bleeding (grade "D") were observed. CONCLUSION:Late postoperative haemorrhage remains a serious complication of tonsil-related surgery with the potential for life-threatening outcomes. The marked variability in bleeding incidence between surgical techniques and departments highlights the need for standardised perioperative protocols. Although no fatalities occurred, the occurrence of severe cases underlines the importance of vigilant postoperative monitoring. In our OSA cohort, tonsillotomy showed favourable safety, and recent evidence suggests it may represent a valuable alternative also in recurrent tonsillitis, warranting further research.
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.
