Causal therapy has achieved success in the treatment of epithelial tumors, which account for more than 80% of all cancers. Although frequently claimed as breakthroughs, cancer therapy has achieved limited increases in su...Causal therapy has achieved success in the treatment of epithelial tumors, which account for more than 80% of all cancers. Although frequently claimed as breakthroughs, cancer therapy has achieved limited increases in survival of only weeks to several months, and cancer incidence continues to increase while metastasis rates, which are primarily responsible for cancer mortality, remain constant. This reflects an incomplete understanding of carcinogenesis and metastatic progression. Over a 25-year timeframe, the series "Epistemology of the Origin of Cancer" has examined the biological basis of carcinogenesis and metastasis. Part I addressed carcinogenesis, Part II identified the first cancer cell, and Part III described the development of local pre-metastatic niches and traveling cancer satellites. In this fourth part, the conditions required for distant metastasis are discussed, including the sequential development of metastatic niches (MN-1, MN-2, and MN-3), transendothelial migration, dormancy, immune modulation, extracellular matrix remodeling, and metastatic niche maturation. The review proposes that metastatic progression depends on the formation of metastatic cancer satellites consisting of metastatic cancer cells, metastasis-associated fibroblasts (MAFs), stromal components, chemokine coatings, platelets, and neutrophil extracellular traps (NETs), each contributing to immune evasion and dissemination. This sequential distant metastatic niche model provides a biological framework explaining clinical observations including metastatic dormancy, relapse after surgery or anticancer therapy, tumor heterogeneity, and the limited long-term success of current therapeutic approaches.
BACKGROUND/AIMS: The management of multiple myeloma (MM), a formidable hematological malignancy, continues to pose substantial challenges. Schisandrin B (Sch B), a bioactive compound derived from Traditional Chinese Medi...BACKGROUND/AIMS: The management of multiple myeloma (MM), a formidable hematological malignancy, continues to pose substantial challenges. Schisandrin B (Sch B), a bioactive compound derived from Traditional Chinese Medicine, has demonstrated potent antitumor properties, but its in vivo effects on MM remain unclear. METHODS: Tumor growth was evaluated by measuring body weight, tumor volume, and cell proliferation. Cell cycle progression and apoptosis were analyzed by flow cytometry. ELISA was performed to quantify interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). Reactive oxygen species (ROS) were detected by immunofluorescence, and Western blotting was used to determine the expression of IL-6, JAK2, phosphorylated JAK2 (p-JAK2), STAT3, and phosphorylated STAT3 (p-STAT3). RESULTS: Sch B markedly inhibited tumor proliferation, induced S-phase cell cycle arrest, and promoted apoptosis. Sch B reduced the expression of IL-6, VEGF, p-JAK2, and p-STAT3 while increasing ROS levels in mice with MM. Moreover, Sch B exhibited a synergistic antitumor effect when combined with bortezomib. CONCLUSION: Schisandrin B represents a promising therapeutic candidate for multiple myeloma, and its antitumor efficacy is further enhanced in combination with bortezomib.
BACKGROUND/AIMS: To present a clinical case of metabolic syndrome (MetS) and to provide a concise pathophysiological overview with emphasis on underlying metabolic and inflammatory mechanisms. METHODS: This study is a ca...BACKGROUND/AIMS: To present a clinical case of metabolic syndrome (MetS) and to provide a concise pathophysiological overview with emphasis on underlying metabolic and inflammatory mechanisms. METHODS: This study is a case report combined with a focused literature review. We describe a patient with MetS who was evaluated and treated at the Hospital of Vietnam National University in Hanoi, Vietnam. RESULTS: A 20-year-old male presented with headaches and palpitations. Clinical examination revealed obesity (BMI 37.1) with a waist circumference of 111 cm, dyslipidemia (triglycerides/HDL-cholesterol/LDL-cholesterol/total cholesterol: 3.84/1.15/4.39/7.29 mmol/L), and hyperglycemia (blood glucose 7.07 mmol/L, HbA1c 7.2%). The patient also exhibited sinus tachycardia and elevated blood pressure, which was confirmed by 24-hour ambulatory blood pressure monitoring. The triglyceride-to-HDL cholesterol ratio was approximately 3.34, indicating insulin resistance and increased cardiovascular risk. Based on these findings, metabolic syndrome associated with obesity, type 2 diabetes mellitus, and hypertension was diagnosed. CONCLUSION: This case highlights the early manifestation of metabolic syndrome and illustrates its underlying pathophysiological mechanisms. Effective management requires early diagnosis, lifestyle modification, weight reduction, and individualized pharmacological therapy to improve metabolic control and reduce long-term cardiovascular risk.
BACKGROUND/AIMS: The Toll-like receptor 4 (TLR4) pathway plays a critical role in mediating inflammatory responses and regulates mitochondrial structural adaptations. Urolithin A (UA), a natural compound that induces mit...BACKGROUND/AIMS: The Toll-like receptor 4 (TLR4) pathway plays a critical role in mediating inflammatory responses and regulates mitochondrial structural adaptations. Urolithin A (UA), a natural compound that induces mito- and autophagy, may improve mitochondrial homeostasis and health. This study examined the effects of UA on TLR4 signaling, mitochondrial dynamics, autophagy, and mitochondrial morphology after lipopolysaccharide (LPS) incubation in C2C12 myotubes. METHODS: C2C12 myotubes were incubated with LPS (1 µg/ml) and/or UA (50 µM). Protein expression related to TLR4 signaling, mitochondrial dynamics, and autophagy was assessed by Western blot, while mitochondrial morphology was evaluated using electron microscopy. RESULTS: LPS-induced inflammation activated downstream TLR4 signaling pathways and altered mitochondrial morphology, including reduced mitochondrial area and circularity. LPS also increased phosphorylation of the mitochondrial fission marker DRP1. UA prevented or attenuated these alterations induced by LPS. CONCLUSION: UA partially mitigates LPS-induced inflammation through modulation of TLR4 signaling and mitochondrial dynamics and may represent a promising therapeutic strategy for disorders associated with mitochondrial dysfunction and inflammation.
Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that occupies a central regulatory position within pulmonary immune networks, integrating inflammatory signalling, redox control, and immune-stromal...Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that occupies a central regulatory position within pulmonary immune networks, integrating inflammatory signalling, redox control, and immune-stromal communication. Originally characterised as a pro-inflammatory mediator, MIF is now recognised to exert context-dependent functions ranging from protective host defence during acute infection to the promotion of chronic inflammation, fibrosis, and tumour progression. This review synthesises current evidence on the molecular biology and signalling mechanisms governing MIF activity in the lung, highlighting its role as a network hub coordinating CD74/CD44- and CXCR-mediated signalling, glucocorticoid antagonism, and redox imbalance. A systems biology perspective illustrates how genetic variability, environmental exposure, ageing, and metabolic stress reprogram MIF-centred immune circuits across pulmonary diseases. Integration of multi-omics and computational modelling identifies opportunities for selective modulation of MIF signalling. Disease-specific roles in pneumonia, COPD, fibrosis, and lung cancer are discussed, positioning MIF as a key immunoregulatory node for future therapeutic strategies.
Neurodegenerative diseases (NDDs) are defined by the gradual degeneration of neuronal cells, wherein the accumulation of misfolded proteins can lead to memory impairments, motor dysfunctions, and other deteriorations. De...Neurodegenerative diseases (NDDs) are defined by the gradual degeneration of neuronal cells, wherein the accumulation of misfolded proteins can lead to memory impairments, motor dysfunctions, and other deteriorations. Despite the widespread impact, there are currently no viable pharmaceuticals to treat these disorders. The mTOR protein is a crucial regulator of cell survival, growth, autophagy, and apoptosis. Targeted modulation of mTOR signaling holds promise for mitigating neurodegeneration in Alzheimer's, Huntington's, ALS, and Parkinson's disease. Understanding its interactions with pathways such as PI3K/Akt, AMPK, and SIRT1 is essential for developing effective therapeutics.
BACKGROUND/AIMS: Brominated flame retardants (BFRs) are widely used synthetic compounds with increasing environmental persistence and toxicological concern. This study investigated acetylcholinesterase (AChE) activity in...BACKGROUND/AIMS: Brominated flame retardants (BFRs) are widely used synthetic compounds with increasing environmental persistence and toxicological concern. This study investigated acetylcholinesterase (AChE) activity in human erythrocytes as a potential biomarker of BFR-induced cellular dysfunction. METHODS: AChE activity was measured spectrophotometrically using Ellman's method after exposure to selected compounds including tetrabromobisphenol A (TBBPA), tetrabromobisphenol S (TBBPS), and bromophenols. RESULTS: TBBPA and TBBPS significantly altered AChE activity, with increased enzyme activity observed at specific concentrations. Among bromophenols, significant effects were detected for 2,4,6-TBP and pentabromophenol. CONCLUSION: The biological effects of BFRs depend on chemical structure and concentration. While erythrocyte AChE responds to exposure, it is not a highly sensitive biosensor, as detectable changes occur alongside other cellular alterations.
BACKGROUND/AIMS: This study aimed to apply ultra-broadband micromechanical ultrasound (UMUS) for correction of myelosuppression caused by the cytotoxic effects of cyclophosphamide without limiting its antitumor efficacy....BACKGROUND/AIMS: This study aimed to apply ultra-broadband micromechanical ultrasound (UMUS) for correction of myelosuppression caused by the cytotoxic effects of cyclophosphamide without limiting its antitumor efficacy. METHODS: The study included animals bearing transplanted Ehrlich carcinoma. Cyclophosphamide (CP) was administered once daily for three consecutive days starting on day 8 of tumor growth at a cumulative dose of 330 mg/kg per mouse. After completion of CP administration, a subset of animals was exposed to UMUS irradiation once daily for five days. Control groups included mice without tumors and tumor-bearing mice not exposed to CP or UMUS. Tumor growth kinetics were analyzed, and quantitative parameters of peripheral blood, bone marrow, and spleen were determined. RESULTS: The obtained data indicate that UMUS exposure does not reduce the antitumor efficacy of CP but is associated with enhanced recovery of the hematopoietic system and exerts a positive effect on bone marrow regeneration. This is confirmed by a statistically significant increase in the number of cells in specific bone marrow hematopoietic pools, including myelokaryocytes, blast cells, erythroid, lymphoid, and megakaryocytic cells. CONCLUSION: UMUS exposure was associated with accelerated recovery of multiple hematopoietic lineages in the bone marrow following cyclophosphamide-induced injury, without compromising antitumor efficacy.
BACKGROUND/AIMS: Rapid and cost-effective quantification of triglycerides remains a challenge in industrial food quality control, where conventional analytical methods are often time-consuming and resource-intensive. Thi...BACKGROUND/AIMS: Rapid and cost-effective quantification of triglycerides remains a challenge in industrial food quality control, where conventional analytical methods are often time-consuming and resource-intensive. This study aimed to develop and characterize an amperometric biosensor based on lipase (LPS) as a biorecognition element for efficient triglyceride detection in vegetable oils. METHODS: Lipase was immobilized onto the electrode surface to catalyze the hydrolysis of glyceryl tributyrate, enabling electrochemical signal generation. Measurements were performed at an applied potential of -600 mV, with a detection time of 7 seconds. The enzymatic reaction rate was derived from the slope of the amperometric signal (mV/s), and calibration was conducted over a concentration range of 1-5 mM. RESULTS: The biosensor demonstrated a strong linear response (R² = 0.998) and high substrate affinity (KM = 0.13 mM). The system exhibited excellent repeatability and specificity, with minimal interference from other triglycerides. Long-term stability studies showed that the immobilized enzyme retained approximately 90% of its activity over 260 days and could be reused up to 27 times without significant performance loss. CONCLUSION: This biosensor represents a robust, rapid, and environmentally friendly analytical platform for triglyceride detection, offering a practical alternative to conventional techniques and strong potential for implementation in routine industrial quality control.
BACKGROUND/AIMS: We explored the fundamental feasibility, technical frame conditions and effectiveness of transcranial Tumor Destructive Mechanical Impulse (TMI) treatment of brain tumors. METHODS: The optimal treatment...BACKGROUND/AIMS: We explored the fundamental feasibility, technical frame conditions and effectiveness of transcranial Tumor Destructive Mechanical Impulse (TMI) treatment of brain tumors. METHODS: The optimal treatment parameters (total energy required, energy flux density, shock wave frequency) and applicator positions were explored and defined with respect to the special conditions given by propagation of shock waves through the skull. RESULTS: As first clinical observations, we present the outcome of transcranial TMI treatment in two cases with brain metastases of malignant melanoma. In both cases, regression of metastases as well in the brain as in other sites was observed, in one of the cases with a complete tumor free recovery. CONCLUSION: In these cases, there were no identifiable signs of impairment of the surrounding brain tissue, and even indications of neuro-regenerative effects as described in the cited experimental literature, so that transcranial TMI treatment of brain tumors may be applied for further systematic investigation without any currently discernible risk for the intact surrounding brain tissue.
BACKGROUND/AIMS: Monitoring lactic acid is a critical parameter during the production of fermented foods, as it serves as an indicator of product quality and process control. The use of biosensors offers a simple and cos...BACKGROUND/AIMS: Monitoring lactic acid is a critical parameter during the production of fermented foods, as it serves as an indicator of product quality and process control. The use of biosensors offers a simple and cost-effective approach for real-time monitoring in the production chain. METHODS: A biosensor based on lactate oxidase (LacOx) was developed to determine lactic acid content in fermented beverages (chicha and pozol). Different membranes were evaluated as immobilization supports, with particular focus on enzyme stability. The system operated at a potential of -0.5 mV, and the amperometric signal was recorded after 10 seconds. Sensor performance was assessed through calibration, sensitivity, and kinetic analysis. RESULTS: The enzymatic reaction rate was directly proportional to oxygen consumption (mg L⁻¹ O₂ s⁻¹), showing a linear detection range between 0.1 and 2 mM (R² = 0.9986). The sensor demonstrated good sensitivity at 0.1 mM and allowed membrane reuse up to 15 times. Enhanced stability was observed when using a cassava biopolymer as immobilization support. The Michaelis-Menten constant (KM = 340 µM) indicated a high affinity of the enzyme for the substrate. CONCLUSION: The developed biosensor provides a reliable, sensitive, and low-cost method for monitoring lactic acid in fermented beverages and represents a practical tool for quality control in the food industry.
BACKGROUND/AIMS: Nosocomial infections continue to be a serious problem in hospital settings, particularly in intensive care units (ICUs), where resistant germs can spread through the air. Air filters are often designed...BACKGROUND/AIMS: Nosocomial infections continue to be a serious problem in hospital settings, particularly in intensive care units (ICUs), where resistant germs can spread through the air. Air filters are often designed to capture particulate matter but not necessarily to kill live germs that remain on their surfaces. MATERIALS: To address these issues, polypropylene filter media were imbued with silver (AgNPs), zinc oxide (ZnO), and copper oxide (CuO) nanoparticles to impart antibacterial activity. Chemical reduction was used to create AgNPs, while sol-gel and precipitation methods were used to prepare ZnO and CuO nanoparticles. RESULTS: DLS and zeta potential measurements were utilized to calculate particle size distribution, polydispersity index, and surface charge. The filters were coated with nanoparticle suspensions by an alcohol-based dip-coating process, followed by heat treatment to solidify the deposited layers. Antibacterial activity was measured against Staphylococcus aureus (ATCC 25923) and Pseudomonas aeruginosa (ATCC 27853) using agar diffusion and direct-contact assays, and reusability was assessed over three cycles. Different variations were observed among the tested materials. Silver nanoparticles demonstrated the largest inhibition zones (18.2 mm for S. aureus and 16.7 mm for P. aeruginosa), followed by copper oxide nanoparticles, which showed moderate inhibition. Under identical conditions, zinc oxide exhibited the lowest inhibition. Over three reuse cycles, AgNP-coated filters retained the majority of the antibacterial activity with minimal decreases in inhibitory zone diameters. ZnO and CuO coatings, on the other hand, showed significantly higher decreases after many cleanings. Treatment of filters with nanoparticles significantly increased antibacterial efficacy compared to untreated controls (p < 0.05). CONCLUSION: In general, the addition of metal nanoparticles to polypropylene filter media appears to improve efficacy in lowering viable airborne bacterial loads. Silver-based coatings exhibited the highest resistance and effective antibacterial response among the studied materials, indicating their potential applicability in ventilation systems for the control of airborne infection within the limitations of the present three-cycle experimental framework.
Sickle cell anemia (SCA) is a progressive, systemic disorder that can lead to multi-organ dysfunction. While it has traditionally been most prevalent in regions where malaria is endemic, recent epidemiological studies ha...Sickle cell anemia (SCA) is a progressive, systemic disorder that can lead to multi-organ dysfunction. While it has traditionally been most prevalent in regions where malaria is endemic, recent epidemiological studies have shown an increasing disease prevalence in non-endemic areas, primarily attributed to global human migration patterns. The severity of SCA typically worsens with age. In early childhood, affected individuals may present with renal hyperfiltration, neurocognitive delays, cardiac remodeling, and skeletal fragility. The presence of these early manifestations often predicts the development of chronic complications later in life, including splenic atrophy, neurodegeneration, and impaired cerebral perfusion. Adequate management of SCA begins with universal newborn screening programs, enabling early detection and the initiation of appropriate interventions. Therapeutic advancements, ranging from disease-modifying agents such as hydroxyurea to curative options including gene therapy and stem cell transplantation, have significantly improved clinical outcomes; however, long-term morbidity remains a significant challenge. This review aimed to explore the effect of aging on pathophysiological changes and the onset of organ-specific complications in SCA patients. It highlights the importance of age-tailored monitoring and a multidisciplinary approach to detect early signs of organ damage, prevent irreversible complications, and consequently improve overall quality of life.
A strong yet appropriate immune response is essential for the timely control and clearing of respiratory viral infections. However, as physical condition declines with age, so does immune function. Immunosenescence is an...A strong yet appropriate immune response is essential for the timely control and clearing of respiratory viral infections. However, as physical condition declines with age, so does immune function. Immunosenescence is an age-related immune dysfunction marked by dysregulation of innate immune pathways, thymic involution, decreased T and B cell numbers and function, altered metabolism, and epigenetic changes. Additionally, older individuals often develop inflammaging, a condition characterized by elevated levels of proinflammatory markers. This deterioration of immune function in older adults significantly impairs viral control and increases disease severity. Studies consistently show a progressive rise in hospitalization and mortality rates with age. This review discusses the complex relationship between aging, immunosenescence, and inflammaging during respiratory viral infections, as well as the underlying mechanisms that increase susceptibility, disease severity, and hospitalization among older adults.
BACKGROUND/AIMS: To assess the relationship between left ventricular remodeling as evaluated by strain echocardiography and conventional echocardiography before and after cardiac resynchronization therapy (CRT) in patien...BACKGROUND/AIMS: To assess the relationship between left ventricular remodeling as evaluated by strain echocardiography and conventional echocardiography before and after cardiac resynchronization therapy (CRT) in patients with severe heart failure. METHODS: A cross-sectional descriptive study with follow-up comparison before and after CRT. The study included 33 heart failure patients indicated for CRT at the Vietnam National Heart Institute, Bach Mai Hospital from late 2015 to December 2021. RESULTS: Left ventricular end-systolic volume and end-diastolic volume significantly decreased after three months of follow-up (p < 0.001) and showed a strong inverse correlation with QRS recovery (r = 0.65). A positive correlation was observed between changes in left atrial volume index (LAVI) and 4B strain (r = 0.96, p < 0.05). After three months of CRT implantation, positive correlations were observed between isovolumic relaxation time (IVRT) and left atrial volume index (LAVI), and between left atrial volume and E/e' obtained from tissue Doppler imaging (r = 0.53, p < 0.05). No correlation was found between E/e' and total EF, between 2B strain and total EF, or between 2B strain and LAVI. CONCLUSION: Strain echocardiography represents an important tool for diagnosing, assessing risk factors, and monitoring heart failure. After three months of CRT implantation, significant improvement in left ventricular volume and ejection fraction was observed, indicating improved treatment effectiveness.
Sundquist S, Lee SR, Johnson A
… +11 more, Lynch HM, Schnell A, Wieskamp S, Peabody HN, Kennington L, Askonas C, Turner C, Hayes D, Hledin M, Lee L, Burnatowska-Hledin MA
BACKGROUND/AIMS: CUL5 acts as the scaffold protein of the E3 ligase complex in ubiquitin-dependent protein degradation pathways. Overexpression of CUL5 inhibits cellular proliferation, whereas inhibition of CUL5 expressi...BACKGROUND/AIMS: CUL5 acts as the scaffold protein of the E3 ligase complex in ubiquitin-dependent protein degradation pathways. Overexpression of CUL5 inhibits cellular proliferation, whereas inhibition of CUL5 expression induces proliferation and may contribute to clinical disorders including cancer. The effects of CUL5 depend on its post-translational modification by NEDD8 (neddylation), a process that represents a potential therapeutic target. This study explores the structure-function relationship between CUL5 and its neddylation status in vitro. METHODS: CUL5 was mutated at the putative neddylation site Lys (K) 724 to Arg (K724RCUL5) and at three potential neddylation sites K724, K727, and K728 (K724R/K727R/K728RCUL5). Because mutation of the PKA phosphorylation site Ser (S) 730 (S730ACUL5) was previously shown to induce neddylation, a K724R/S730ACUL5 mutant was also generated. Mutant and wild-type constructs were expressed in rat endothelial cells (RAMEC), T47D cancer cells, and COS-1 cells. Cellular proliferation, MAPK phosphorylation, ERα expression, and CUL5 neddylation status were analyzed, including treatment with the neddylation inhibitor MLN4924. RESULTS: Expression of wild-type CUL5 attenuated cell growth in RAMEC, T47D, and COS-1 cells. In contrast, expression of K724RCUL5 and K724R/S730ACUL5 mutants induced cellular growth, whereas the K724R/K727R/K728RCUL5 mutant had no significant effect on proliferation. In T47D cells, MAPK phosphorylation and estrogen receptor (ERα) expression were directly correlated with the neddylation status of CUL5. Western blot analysis of COS-1 cells treated with MLN4924 demonstrated that CUL5 remained neddylated in all mutant cell lines. CONCLUSION: These findings suggest that modification of CUL5 by NEDD8 may occur at multiple lysine residues and that multi-site neddylation may contribute to the diverse regulatory effects of CUL5 on cellular signaling and proliferation.
BACKGROUND/AIMS: Infection with Helicobacter pylori is a major cause of chronic gastritis and persistent gastric inflammation. miRNA-155 and inflammatory cytokines play key roles in immune regulation; however, their syst...BACKGROUND/AIMS: Infection with Helicobacter pylori is a major cause of chronic gastritis and persistent gastric inflammation. miRNA-155 and inflammatory cytokines play key roles in immune regulation; however, their systemic expression profiles in H. pylori-associated chronic gastritis are not fully characterized. METHODS: Twenty-five patients with endoscopically and histologically confirmed H. pylori-associated chronic gastritis and 25 age-matched healthy controls were included. Peripheral miRNA-155 expression was measured by quantitative real-time PCR, and serum IL-6, IFN-γ, and IL-10 levels were quantified by ELISA. RESULTS: Patients exhibited significantly elevated peripheral miRNA-155 expression compared with controls (p < 0.001). Serum IL-6, IFN-γ, and IL-10 concentrations were also significantly higher in patients (all p < 0.001). Logistic regression analyses indicated significant associations between biomarker levels and H. pylori infection status. CONCLUSION: This exploratory case-control study demonstrates systemic alterations in miRNA-155 expression and inflammatory cytokines in H. pylori-associated chronic gastritis. These findings suggest immune-regulatory changes detectable in peripheral blood, warranting validation in larger independent cohorts.
BACKGROUND/AIMS: Nanobiotechnology offers sustainable strategies to enhance plant resistance by activating innate immune responses. This study evaluates the effect of chitosan nanoparticles (CNPs) on transcriptional acti...BACKGROUND/AIMS: Nanobiotechnology offers sustainable strategies to enhance plant resistance by activating innate immune responses. This study evaluates the effect of chitosan nanoparticles (CNPs) on transcriptional activation of defense-associated genes in Arabidopsis thaliana. METHODS: CNPs were produced via ionic gelation and sprayed on leaves of 4-week-old plants. Relative expression levels of PR1, PDF1.2, and WRKY70 were measured using qRT-PCR and the 2^-ΔΔCt method with normalization and statistical analysis. RESULTS: CNP treatment significantly increased PR1, PDF1.2, and WRKY70 expression compared to controls, indicating activation of salicylic acid and jasmonic acid/ethylene signaling pathways. WRKY70 showed the highest induction, suggesting a major regulatory role in coordinating defense signaling. CONCLUSION: Chitosan nanoparticles act as effective inducers of transcriptional activation of plant defense markers in Arabidopsis thaliana. Mechanisms including ROS signaling, calcium influx, MAPK cascades, and PTI/ETI responses warrant further investigation.
BACKGROUND/AIMS: Systemic sclerosis is a rare autoimmune and fibrotic disease, often manifesting in the skin. The aryl hydrocarbon receptor is critical for skin homeostasis; however, its role in fibrosis is not well unde...BACKGROUND/AIMS: Systemic sclerosis is a rare autoimmune and fibrotic disease, often manifesting in the skin. The aryl hydrocarbon receptor is critical for skin homeostasis; however, its role in fibrosis is not well understood. We investigated the crosstalk between TGFβ, AHR, and Wnt/β-catenin signaling. METHODS: Human dermal fibroblasts and HaCaT keratinocytes, both wild-type and AHR-deficient, were cultured in mono- and co-cultures. Cells were treated with TGFβ and the AHR agonist FICZ. Collagen type I and MMP1 were quantified, Wnt/β-catenin genes analyzed, migration assessed, and proteome profiling performed. RESULTS: AHR deletion reduced Wnt/β-catenin gene expression and abrogated TGFβ-induced collagen production. Co-cultures showed AHR-dependent regulation of immune-related genes, and scratch closure was also AHR-dependent. CONCLUSION: The study demonstrates a context-dependent role of AHR in skin fibrosis and its interaction with TGFβ and Wnt/β-catenin signaling.
BACKGROUND/AIMS: To explore the feasibility and effectiveness of Tumor Destructive Mechanical Impulse (TMI) treatment of solid tumors, biomechanical preconditions for subsequent computational simulation of focused shock...BACKGROUND/AIMS: To explore the feasibility and effectiveness of Tumor Destructive Mechanical Impulse (TMI) treatment of solid tumors, biomechanical preconditions for subsequent computational simulation of focused shock wave propagation within cells and tissue are investigated. This innovative "soft" approach is different from the FDA-approved high intensity focused ultrasound (HIFU)-based histotripsy, and from electrical Tumor Treating Fields (TTFs). METHODS: Atomic force microscopy investigation for cell mechanics, multiple parametric computational simulations for focused shock wave propagation, technical TMI generator and applicator design, light- and electron-microscopic evaluation of treatment effects on tumor cells and tissue. RESULTS: Individual tumor cell evaluation of physical properties as basis for multiple parametric simulations determine the optimal treatment parameters (total energy required, energy flux density, shock wave frequency) and applicator positions; design flexibility of applicator devices for extra- and intracorporeal treatment. CONCLUSION: The fundamental feasibility, effectiveness and reliability of TMI treatment of solid tumors were proven, providing a reliable theoretical basis for the broadly applicable translation into clinical practice.