Mutations in RAS and PI3K pathway genes play a critical role in Colorectal Cancer (CRC) pathogenesis and therapy response, yet data from underrepresented populations remain limited. Molecular analysis was performed on 48 CRC cases from the Kurdistan region of Iraq to detect mutations in KRAS and NRAS (codons 12, 13, 59, 61, 117, and 146; exons 2–4), BRAF (codon 600; exon 15), PIK3CA (codons 542, 545, and 1047; exons 9 and 20), and AKT1 (codon 17; exon 4), and to correlate findings with histopathological characteristics and survival outcomes. NRAS mutations were the most frequently detected alterations (52.08%), followed by KRAS (47.92%) and PIK3CA (16.67%). A high frequency of co-mutations, particularly involving KRAS and NRAS, was observed, substantially exceeding frequencies reported in international cohorts; possible contributing factors including intratumoral heterogeneity and assay sensitivity are discussed. Tumor-associated inflammatory response and lymph node status demonstrated significant associations with patient survival. These findings from a small patient cohort suggest the need for further investigation of regional CRC molecular profiles using larger cohorts and orthogonal validation methods.
Colorectal Cancer (CRC) is one of the most common malignancies globally, and its increasing prevalence in Iraq is an emerging health problem. This work analyzed the expression profiles of miR-205 (microRNA-205), BCL2 (B-cell lymphoma 2), and YAP1 gene in Iraqi CRC patients to evaluate the potential contribution towards diagnosis and prognosis. Eighty individual CRC and 40 healthy Control patients were recruited. Complete Blood Count (CBC) analysis was performed to assess White Blood Cell (WBC) concentrations, and Interleukin-18 (IL-18) and Interleukin-22 (IL-22) concentrations were determined by Enzyme-Linked Immunosorbent Assay (ELISA). Quantitative real-time Polymerase Chain Reaction (qRT-PCR) was utilized to quantify expression levels of miR-205, BCL2, and YAP1. Diagnostic efficacy was established by performing Receiver Operating Characteristic (ROC) curve analysis, and biomarker associations were evaluated using Pearson correlation. Differences in WBC count levels, IL-18, and IL-22 levels were non-significant in patients vs. controls. In contrast, miR-205 expression was significantly decreased in CRC patients (0.33-fold), whereas BCL2 and YAP1 were significantly up-regulated (1.92-fold and 1.44-fold, respectively). ROC analysis revealed that BCL2 showed the greatest diagnostic activity, with an area under the curve (AUC) of 0.880, and was followed by YAP1 (AUC: 0.736) and miR-205 (AUC: 0.700). There were significant correlations between miR-205/BCL2 and BCL2/YAP1, indicating coordinated roles in apoptosis blocking and tumor growth mechanisms. Collectively these results recommend the tumor suppressive role of miR-205 and the oncogenic role of BCL2 and YAP1 which could explain CRC phenotypes and therapy resistance. Overall, the study d=also suggest the potential of these genes as cancer detection candidate in the Iraqi population even within its limitations.
The Apriori algorithm is a data mining algorithm used exclusively for identifying associations between itemsets in a series of business transactions. In this paper, we modify this algorithm to identify associations between trinucleotide repeat expansions in DNA, which are known for their associations with specific genetic diseases. The proposed modification here is to treat all possible forms of DNA trinucleotides as item sets and the list of all DNA segments as a series of transactions. In the first iteration of the algorithm, the number of occurrences of every single trinucleotide is counted across all DNA segments. Then, the results are filtered out according to a preset threshold. In the second iteration, the number of occurrences of every pair of trinucleotides is counted, and similarly, the results are filtered out according to a threshold. In the third iteration, the number of occurrences of every trio of trinucleotides is handled similarly. The algorithm continues until no results are produced. Lastly, the association rules are formed, yielding the conclusion of the existence of a certain genetic disease will also mean an existence of another genetic disease.
ROR1 kinase is an underexplored yet promising target for the development of novel anticancer agents, as it is highly expressed in several cancer cell lines while showing limited expression in non-tumor cells. This selective expression, together with the limited number of effective ROR1 inhibitors currently available, motivated the design and development of a research program aimed at identifying new chemical entities capable of inhibiting ROR1 and interfering with its protumoral activity. Step-by-step in silico studies guided the design and synthesis of para-phenylenediamine-based compounds. The synthesized derivatives were first evaluated for their ability to directly bind the ROR1 kinase domain using surface plasmon resonance (SPR) assays, allowing the selection of the most promising candidates for cellular studies. Antiproliferative activity was then assessed in SH-SY5Y neuroblastoma and JeKo-1 mantle cell lymphoma cell lines, revealing a markedly stronger effect in JeKo-1 cells. Based on this higher sensitivity, further biological investigations were performed in JeKo-1 cells, demonstrating a significant induction of apoptosis upon treatment. Cellular studies confirmed direct ROR1 engagement and a consequent reduction in its phosphorylation, leading to modulation of downstream survival signaling pathways and activation of pro-apoptotic mechanisms. Among the synthesized compounds, derivative 17 emerged as the most promising candidate, also displaying a favorable in vitro pharmacokinetic stability profile. Overall, these findings identify compound 17 as a novel chemotype targeting ROR1, providing a solid basis for further structure–activity relationship optimization and hit-to-lead development.
Hypoxia is a common feature of hepatocellular carcinoma (HCC) and shapes tumour behaviour by selecting for cells able to withstand low oxygen availability, redox imbalance, and nutrient limitation [1]. Although hypoxia-driven signalling is typically studied through HIF-dependent transcriptional programs, less is known about how cyclic nucleotide pathways contribute to these adaptations. Phosphodiesterase-5A (PDE5A), a key cGMP-hydrolyzing enzyme and the pharmacological target of sildenafil, is increasingly implicated in cancer biology, but its possible role in supporting HCC cell survival under hypoxic stress remains unclear. Under physiological conditions, PDE5A expression in the liver is restricted to the centrilobular zone, a naturally hypoxic region; conversely, HCC displays marked PDE5A upregulation with loss of zonal specificity, consistent with a functional role in tumour adaptation to low oxygen tension. Here, we investigated PDE5A regulation and function in HCC cell lines (HepaRG, HepG2, Huh7) exposed to hypoxia (1% O₂), hypoxia-mimicking conditions (CoCl₂, deferoxamine), and oxidative stress (H₂O₂). Across models, both real and simulated hypoxia significantly increased PDE5A protein expression and activity, while mitochondrial ROS-driven oxidative stress further enhanced PDE5A levels, indicating a dual regulatory mechanism involving both HIF activation and redox-dependent signals. Hypoxia was validated by HIF-1α stabilization and increased lactate dehydrogenase activity. More aggressive cell lines exhibited the highest PDE5A activity and expression, consistent with an association between PDE5A levels and malignant features. To strengthen the mechanistic link between hypoxia-responsive transcriptional programs and PDE5A, in silico analyses (TCGA-LIHC/GEPIA2) revealed positive correlations among HIF1A, SP1, and PDE5A expression, and motif scanning (FIMO) identified multiple high-confidence Sp1 binding sites within the PDE5A genomic region [2]. Consistent with this model, pharmacological inhibition of Sp1 with mithramycin reduced PDE5A expression under hypoxia, supporting a hypoxia-Sp1-PDE5A regulatory axis. To assess PDE5A’s role in hypoxia-mediated survival signalling, we inhibited PDE5A with sildenafil during hypoxia. PDE5A inhibition led to a clear reduction in MAPK/ERK pathway activation compared with hypoxia alone, accompanied by increased expression of pro-apoptotic markers, including BAX. Taken together, our data indicate that PDE5A supports hypoxic HCC cell survival by sustaining ERK-dependent pro-survival signaling, whereas PDE5A blockade shifts the balance toward apoptosis. These findings position PDE5A as a relevant mediator of hypoxia-driven adaptation in HCC and a potential therapeutic vulnerability to disrupt stress tolerance in the hypoxic tumour compartment. Ongoing work using CRISPR/Cas9-mediated PDE5A knockout will test causality and refine the PDE5A-ERK-apoptosis framework.
Introduction The PLASTAMINATION Congress held on 13 February 2026 at the University of Palermo, convened a multidisciplinary panel of experts to address the escalating challenge of micro- and nanoplastic (MNP) contamination. Characterized during the session as a silent invasion MNP pollution represents a systemic threat that bridges environmental degradation and human pathology. This round table synthesized perspectives on the entire plastic lifecycle: from urban point sources and regional monitoring to ecotoxicological risks and advanced materials engineering. The discussion underscored that the traditional conceptual boundary between the environment and the human organism is no longer sustainable, necessitating a coordinated scientific and institutional response grounded in the One Health framework. Science communication and public responsibility The round table opened with a reflection on the role of science communication and public responsibility, moderated by Giorgia Görner Enrile, journalist for SciliaMedica.it and ilSicilia.it, who framed the discussion around the relationship between scientific knowledge, information, and society. Communicating health today means more than sharing scientific results, because communication itself carries an ethical responsibility toward society. The III PLASTAMINATION Conference 2026 and the project PLASTAMINATION Poly (Lactic Acid) plastics contamination therefore address not only the issue of plastic and MNP contamination, but also the way scientific evidence reaches the public and the effects it may generate in terms of trust, fear, or awareness. The One Health perspective reminds us that environmental, animal, and human health remain deeply interconnected, but it also highlights the responsibility involved in communicating these topics, since scientific data and research findings can easily enter public debate and sometimes become instrumentalized within environmental, social, or political narratives. Public discussion does not necessarily represent a problem, but difficulties arise when the complexity of scientific research becomes reduced to simplified messages or slogans. This dynamic becomes even more evident within the contemporary information ecosystem, where media attention often focuses on headlines rather than on scientific context, while information increasingly circulates through social networks whose visibility mechanisms depend more on algorithms than on the reliability of sources. In this environment, communication about health and environmental risks should not only inform but also encourage critical thinking, helping people recognize reliable information and distinguish between evidence, interpretation, and sensationalism. Transparency therefore plays a crucial role in scientific and institutional communication, but transparency does not mean oversimplification or reassurance at any cost, since trust grows from clarity and from the recognition of the limits that accompany scientific knowledge. Environmental monitoring and infrastructure vulnerabilities Effective mitigation of marine plastic pollution begins with robust environmental surveillance and standardized monitoring programmes. Dr. Salvatore Campanella and Dr. Alessandro Aglialoro, ARPA Sicilia, presented the environmental monitoring activities carried out by the regional agency within the framework of the Marine Strategy Framework Directive (MSFD, Directive 2008/56/EC). This European policy instrument aims to achieve and maintain the Good Environmental Status (GES) of marine waters through coordinated monitoring systems implemented by Member States and supported in Italy by the Ministry for the Environment, ISPRA, and the National System for Environmental Protection (SNPA). Within this framework, ARPA Sicilia conducts periodic monitoring campaigns in coastal and offshore waters using standardized sampling protocols. These surveys include the collection and analysis of seawater, marine sediments, and biological matrices (biota) in order to assess environmental quality and detect the presence of anthropogenic contaminants. Monitoring activities also address the distribution of marine litter and microplastics, including the assessment of floating debris, beached litter, and microplastic particles in the water column and sediments, as required by the indicators of Descriptor 10 (Marine Litter) of the Marine Strategy. The data generated through these monitoring programmes contribute to national and European environmental reporting systems and support the scientific assessment of the ecological status of the Mediterranean Sea. These datasets provide an essential basis for environmental policy, risk assessment, and the development of mitigation strategies at both national and European levels. In addition to monitoring activities, ARPA Sicilia participates in international scientific cooperation initiatives and promotes environmental education and awareness programmes, including outreach activities aimed at schools and local communities, with the objective of increasing public understanding of marine pollution and fostering sustainable environmental practices. However, the urban origin of plastic contaminants remains a critical factor in their transfer to aquatic environments. Prof. Michele Torregrossa (University of Palermo) highlighted the dual role of wastewater treatment plants (WWTPs) in the environmental dynamics of microplastic pollution. On the one hand, conventional wastewater treatment processes, including primary sedimentation, biological treatment, and secondary clarification, together with advanced technologies such as membrane bioreactors (MBRs), are capable of removing a substantial fraction of microplastics from treated effluents. Several studies report removal efficiencies frequently exceeding 90% for larger microplastic particles, although efficiency depends on particle size and plant configuration. On the other hand, WWTPs act as accumulation points for microplastics, since most of the particles retained during treatment are transferred to sewage sludge. This creates a secondary environmental concern, particularly when sludge is reused in agriculture or disposed of in landfills, potentially reintroducing microplastics into terrestrial ecosystems. The situation may be further exacerbated by extreme weather events associated with climate change. During intense rainfall, combined sewer systems may generate Combined Sewer Overflows (CSOs), temporarily bypassing wastewater treatment plants and discharging untreated wastewater directly into receiving water bodies. Under these conditions, several studies have reported that microplastic concentrations in urban runoff and CSO discharges can be up to 5 or 10 times higher than those measured in treated wastewater effluents. This increase is mainly related to the wash-off of urban surfaces, the mobilization of plastic particles accumulated within sewer networks, and the resuspension of sediments during high-flow conditions. These findings highlight the need for integrated management strategies addressing both urban wastewater infrastructure and plastic pollution mitigation, in order to reduce the transfer of microplastics from urban systems to aquatic environments. Biological risks From Ecotoxicology to Human Health The transition of plastics from environmental matrices to biological tissues was a central theme. Prof. Federica Scalia (UniKore) presented evidence regarding the invisible risks of biodegradable polymers, specifically Polylactic Acid (PLA). Utilizing the zebrafish model, her research demonstrated that PLA nanoplastics can bioaccumulate in zebrafish, especially in the gastrointestinal system, within 120 hours post-fertilization. These exposures were linked to significant gene expression alterations, specifically in cellular stress markers, suggesting that eco-friendly alternatives require rigorous toxicological scrutiny during embryonic development. These findings resonate with the human health perspectives shared by Prof. Stefania D’Angelo (Parthenope University of Naples). MNPs have shifted from being external contaminants to internal systemic constituents, detected in the lungs, liver, placenta, and brain. The discussion detailed how MNPs trigger oxidative stress, chronic inflammation, and the disruption of critical biological barriers. Of particular clinical concern is the presence of MNPs within atherosclerotic plaques, which is increasingly associated with a higher risk of major cardiovascular events, and their potential role in neuroinflammatory processes related to dementia. Circular solutions and materials science To counter these threats, the panel explored resilient technological pathways. Prof. Annamaria Visco (University of Messina), principal investigator of the European LIFE RESTART project, presented an applied model of circular economy in the field of polymeric materials, based on the valorization of agro-industrial by-products and their integration into biodegradable polymer matrices. The project, funded under the LIFE Programme of the European Union, aims to develop sustainable composite materials obtained from residual biomass derived from agricultural and agro-industrial supply chains, contributing to the reduction of fossil-based raw materials and promoting new circular production models. The research activities carried out by the University of Messina research group have led to the development of polymeric biocomposites obtained by incorporating plant residues and agro-industrial by-products into biodegradable matrices. This approach allows the valorization of organic waste streams, transforming them into high-value materials, while simultaneously reducing the environmental impact associated with conventional plastic production. A key element of the project is the establishment of the “Fabbrica Zero” pilot plant in Roccavaldina (Messina), a demonstration facility designed to transfer laboratory research results to an industrial scale. Within this framework, materials developed in academic laboratories are processed through technologies compatible with existing industrial transformation processes, demonstrating the technical feasibility of producing biocomposites from residual biomass. During the discussion, the economic dimension also clearly emerged as a critical factor influencing the large-scale adoption of these materials. The development and production costs of sustainable biocomposites are currently higher than those of conventional fossil-based plastics, particularly during the early phases of technological deployment. As a result, many companies face significant challenges in independently sustaining the transition toward more sustainable materials. It was therefore highlighted that a structural transformation of production systems requires not only scientific innovation but also targeted policy measures and economic incentives capable of supporting companies in adopting environmentally sustainable materials and processes. In this context, Prof. Andrea Pace (University of Palermo) emphasized that the development of new materials must be framed within a broader perspective integrating scientific research, industrial policies, and innovation governance. According to Pace, the transition toward more sustainable polymeric materials cannot rely solely on technological progress but requires the creation of innovation ecosystems in which universities, research centers, industries, and public institutions collaborate in a coordinated and structured manner. It emerged that strengthening technology transfer mechanisms, supporting applied research, and developing dedicated funding instruments could play a crucial role in accelerating the integration of sustainable materials into industrial systems. In this perspective, policy tools such as incentives for companies adopting low-impact materials, green public procurement strategies, and innovation programmes promoted at the European level could significantly reduce the economic barriers that still limit the widespread adoption of these technologies. Finally, Dr. Dario Scalia, Plastic Free Onlus highlighted the crucial role of civil society in addressing plastic pollution. Alongside technological solutions and industrial policies, environmental volunteering initiatives, awareness campaigns, and territorial clean-up activities represent concrete tools to reduce plastic dispersion in natural ecosystems and to promote collective responsibility in environmental protection. During the discussion, the importance of environmental education targeting younger generations was also strongly emphasized. Educational programmes in schools, awareness initiatives, and participatory activities involving students represent key instruments for fostering a culture of sustainability from an early age. It emerged that engaging children and young people in environmental education initiatives can play a fundamental role in shaping long-term behavioral change and in promoting responsible attitudes toward environmental protection. Conclusion The PLASTAMINATION round table concluded that the fight against plastic contamination requires an integrated, multi-scalar approach. Enhancing the filtration capacity of WWTPs is insufficient if the resulting sludge is not managed or if materials are not designed for sustainability from their inception. The detection of epigenetic impacts and the systemic accumulation of plastics in vital human organs mandate a paradigm shift: plastic is no longer merely a waste management issue but a critical determinant of global public health.
Selective inhibition of histone deacetylases (HDACs) has gained increasing attention as a promising strategy for antitumor targeted therapy [1]. HDAC6, a member of the HDAC family, deacetylates non-histone proteins and modulates several cellular processes, including lipid metabolism [2]. HDAC6 is involved in the development and progression of colorectal cancer (CRC) and is associated with poor prognosis. The selective HDAC6 inhibitor ITF3756 reduced the viability of HCT116 and HT29 colon cancer cells while inducing lipid accumulation. Based on the involvement of HDAC6 in lipid metabolism control, ITF3756 was combined with bortezomib (BTZ), a proteasome inhibitor known to promote lipogenesis [3]. At subtoxic doses, the combined treatment of ITF3756 and BTZ exerted a synergistic pro-apoptotic effect in HCT116 cells. Interestingly, the combination enhanced lipid synthesis as shown by Oil Red O staining, which was associated with mTOR phosphorylation, SREBP-1 activation, and increased PPARγ expression. The ITF3756/BTZ combination was less effective in HT29 cells, which exhibited high basal levels of lipid droplets. Inhibition of diacylglycerol acyltransferase 1 (DGAT-1) and 2 (DGAT-2) suppressed lipogenesis and potentiated the effects of the ITF3756/BTZ combination in both cell lines, suggesting that lipid accumulation acts as a protective mechanism. This hypothesis was further supported by SREBP-1 silencing, which also enhanced the antitumor efficacy of the ITF3756/BTZ combination in HCT116 cells. Overall, these findings highlight the promising antitumor activity of the selective HDAC6 inhibitor when combined with BTZ in colon cancer cells and suggest that the combination with anti-lipogenic compounds may represent a nice tool for potential clinical applications.
Hormonal fluctuations throughout a woman’s life, from puberty to menopause, profoundly influence the composition of the vaginal and gut microbiota, with major implications for reproductive, metabolic, and psychological health. Recent findings indicate that lifestyle factors, such as diet, stress, sleep, and physical activity, modulate microbial communities and hormonal balance through an integrated microbiome–immune–endocrine axis. This review examines the evolution of the vaginal microbiota, the effects of hormonal changes on microbial balance, and evidence for probiotic and lifestyle-based interventions in conditions such as bacterial vaginosis, endometriosis, polycystic ovary syndrome, pregnancy complications, and menopausal disorders. Particular attention is given to the estrobolome, gut–brain communication, and metabolic regulators as mediators of systemic effects.
Biological research is moving away from isolated observations. The current priority is integrating different layers of data to build practical interventions. Whether dealing with a metabolic diseases, an environmental crisis, or drug resistance, we need a combination of early diagnostic tools and targeted therapies. The papers published in this issue of the Journal of Biological Research focus precisely on this transition, covering clinical medicine, toxicology, and environmental biotechnology. Early screening remains the most effective way to prevent irreversible tissue damage. This is clear in the study on type 2 diabetic nephropathy.¹ Microalbuminuria has well-known analytical limits, which is why attention is shifting to serum cystatin C and beta-2 microglobulin. Evaluating these two markers alongside the estimated glomerular filtration rate gives clinicians a much tighter window for early intervention.¹ Diagnostic accuracy is equally critical when managing thyroid nodules.² A direct comparison between the American Thyroid Association (ATA) guidelines and the ACR TI-RADS lexicon shows how standardizing ultrasound data reduces ambiguity in fine-needle aspiration decisions.² [...]
Helicobacter pylori (H. pylori) is a main cause of chronic gastritis, peptic ulcers, and gastric cancer. Despite available treatments, eradication fails in 5–20% of cases, with frequent ulcer recurrence. This highlights the need for alternative therapies, including plant-derived natural products. Therefore, this study aims to evaluate the antibacterial effects of pomegranate peel extracts on H. pylori growth. This is a pilot study in which gastric biopsies were collected from H. pylori-positive patients at a single center. Fresh pomegranate (Punica granatum) peels were extracted with 80% methanol using ultrasonic-assisted extraction. Following filtration and concentration, extracts were examined for the presence of bioactive compounds. H. pylori were grown on brain–heart infusion broth, and the identification was confirmed by evaluating colony morphology, Gram stain, and urease, catalase, and oxidase activity. Antibacterial activity of peel extracts (3–10 milligrams per milliliter) was assessed via inhibition zones, and minimum inhibitory and minimum bactericidal concentrations were determined. Eight gastric biopsies were analyzed. All isolates (100%) were resistant to amoxicillin and amoxicillin-clavulanate, while fully susceptible to levofloxacin and ciprofloxacin, with inhibition zones of 18–29 mm and 18–27 mm, respectively. Pomegranate peel extract was found to exhibit a dose-response relationship in antibacterial activity against tested isolates when used in concentrations of 3, 5, 7, and 10 mg/mL. Inhibition zones ranged from complete inhibition (one isolate) to 24 mm at 3 mg/mL; from complete inhibition (one isolate) to 30 mm at 5 mg/mL; from complete inhibition (one isolate) to 32 mm at 7 mg/mL; and from 15 to 27 mm at 10 mg/mL. Pomegranate could be used as a natural therapeutic agent to establish novel strategies in the prevention of H. pylori infection and antibiotic resistance.
Diabetic foot ulcers are among the most common problems facing the people with diabetes. Leukocytes have been shown to penetrate the region of inflammation in order to regulate the infection. Thus, the current research was designed to study the infiltration of leukocytes in diabetic foot patients. Samples were taken from 50 healthy individuals and 100 diabetic foot ulcer patients. Levels of Fasting Blood Sugar (FBS), Hemoglobin A1C (HbA1c), cholesterol, triglycerides, urea, and creatinine were measured. Leukocytes infiltration was also evaluated in the diabetic foot patients. Levels of FBS and HbA1c were significantly increased (p≤ 0.05) in patients with diabetic foot ulceration. In addition, the levels of cholesterol, triglycerides and urea significantly increased (p≤ 0.05) in diabetic foot ulceration patients. However, the levels of creatinine greatly decreased in patients with diabetic foot ulceration. Infiltrated leukocytes were significantly increased in the ulcerated foot. Furthermore, the study found a strong association between leukocyte infiltration and HbA1c as follows: (y = 0.6864x + 0.9455: R² = 0.776). Thus, studying the mechanism of controlling leukocytes in diabetic foot ulcer could greatly participate in healing of diabetic foot ulcers.
MicroRNA (miRNA) is a key regulator of gene expression, involved in modulating various physiological and pathological processes. Current research primarily focuses on the regulatory mechanisms of miRNA targeting the 3' untranslated region (3'UTR), while understanding of its functional mode when targeting the protein-coding sequence (CDS) remains limited. This study established an exogenous gene expression system to systematically compare the regulatory differences in gene expression between the miRNA-3'UTR and miRNA-CDS targeting modes. Western blotting and fluorescent reporter analyses confirmed that both modes effectively suppressed protein expression, but miRNA-mediated suppression targeting CDS responded more rapidly. Real-Time Polymerase Chain Reaction (RT-PCR) analysis further revealed that the miRNA-3'UTR mode led to significant downregulation of mRNA levels, whereas the miRNA-CDS mode induced only a transient and mild reduction in mRNA. Collectively, these results demonstrate that the mechanism of miRNA action is position-dependent: targeting the 3'UTR primarily induces mRNA degradation, while targeting the CDS preferentially inhibits the translation process. This model provides an experimental framework for deciphering new mechanisms of miRNA-mediated gene expression regulation and lays a foundation for functional studies of non-coding RNAs and related disease mechanisms.
Cnidarians are considered the most ancient venomous phylum on Earth. Their venom is a complex mixture of bioactive compounds that produce a myriad of signs and symptoms in humans. Additionally, studies have revealed the presence of molecules with remarkably pharmacological potential as modulators of immune responses and ion channels. Herein, we have used Superior Cervical Ganglion (SCG) neurons to assess the effects of five cnidarian species on the action potential firing. Although all venoms tested significantly slowed down the firing rate, differential underlying mechanisms were observed between anthozoan and cubozoan species. These findings show the presence of neurotoxins in all five cnidarian species as modulators of neuronal excitability and reveal differential mechanisms between anthozoans and cubozoans. The underlying mechanisms, likely involving changes in receptors and ion channel kinetics, are key pieces in advanced drug design with clinical purposes.
Primary prevention is particularly relevant for young adults experiencing major life changes that may affect their health. This cross-sectional study aimed to assess the physical condition and lifestyle of first-year university students, with a focus on differences by sex and area of origin (urban or rural). The sample consisted of 315 students (59% female, 41 % male; aged 18-25). Of these, 159 (62% female) were from urban areas, while 156 (57% female) were from rural areas. Anthropometric characteristics, body mass index, waist-to-height ratio and Handgrip Strength (HGS) were measured; Fat Mass (FM%), Fat Free Mass (FFM%) and Muscular Mass (MM%) were estimated through bioelectrical impedance vector analysis. Physical activity and the adherence to the mediterranean diet were also assessed. Males showed significantly higher values than females in all anthropometric traits, body composition, HGS and moderate-to-vigorous physical activity. Rural males reported lower FM% and higher MM% than urban males. Rural groups had a lower prevalence of being overweight. Our findings suggest an association between environmental context and certain body measurements, particularly in males.
Over the past 70 years, veterinary vaccines have been crucial in controlling infectious diseases, ensuring food security, improving animal health, and promoting public health. This paper examines the global decline in morbidity and mortality in livestock and wildlife due to vaccination campaigns from 1950 to 2021. Data were gathered from peer-reviewed studies, international reports, case studies, and organizations such as the Food and Agriculture Organization (FAO). These sources helped assess trends in disease epidemiology and demonstrate vaccination’s vital role in controlling or eradicating animal diseases and reducing zoonotic risks. Diseases studied include foot-and-mouth disease, rinderpest, avian influenza, and rabies. Findings show that global vaccination eradicated rinderpest in animals and wildlife, while foot-and-mouth disease and avian influenza declined by over 90% and 60%, respectively. The campaigns also prevented billions of dollars in economic losses annually by reducing outbreaks and mortality. This underscores the importance of sustained funding for veterinary vaccination programs to protect animal populations and human health alike.
This study explored the anti-inflammatory potential of Quantum Molecular Resonance (QMR) technology using an in vitro model of osteoarthritis-associated inflammation. Inflammatory cytokine production and nitrosative stress were induced in THP-1-derived macrophages by lipopolysaccharide and hyaluronic acid fragments stimulation. The expression and activity levels of COX-2 and iNOS were both decreased by QMR exposure, along with a significant attenuation of NF-κB signaling. Furthermore, QMR treatment had a significant impact on decreasing peroxynitrite levels, which are reactive nitrogen species generated under inflammatory conditions, and restoring tyrosine nitration levels to levels that were similar to those observed in cells treated with sham. QMR was analyzed for its effects on inflammasome activation and macrophage polarization. NLRP3 and active caspase-1 protein levels were significantly decreased by QMR treatment, which was also associated with reduced expression and release of IL-18 and IL-1β. Finally, our results demonstrated that QMR treatment promotes a shift in macrophage polarization from the M1 to the M2 phenotype.
The treatment of solid tumors has undergone significant changes over the years. Traditional chemotherapy has gradually been abandoned in favor of innovative therapeutic approaches that have improved patient survival and quality of life. Precision medicine, using targeted therapies, immunotherapy, antibody-drug conjugates (ADCs), and tumor-agnostic therapies, is now commonplace. Modern molecular biology techniques have allowed us to better understand cancer, thanks to the identification of countless driver mutations (EGFR, ALK, BRAF, MEK, RET, ROS1, PARP). Targeted therapies have been developed, resulting in improved prognosis (particularly osimertinib, alectinib, dabrafenib, trametinib, selpercatinib and PARP inhibitors). Immunotherapy has revolutionized both cancer research and treatment by using the patient's own immune system to eradicate cancer and prevent recurrence. Antibodies are used to block immunosuppressive molecules, such as antibodies directed against the protein PD-1 (Programmed Cell Death-1), the protein PD-L1 (Programmed Death-1) ligand, and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) in several solid tumors, including pembrolizumab, nivolumab, cemiplimab and ipilimumab. Antibody-drug conjugates (ADCs) are cancer therapies that combine 3 components: 1) monoclonal antibodies designed to specifically target on cell surface; 2) cytotoxic chemotherapy (payload) that destroy cancer cells while sparing healthy tissue; 3) linker that attaches the payload to the antibody only releasing the payload at the desired target. Trastuzumab emtansine, Trastuzumab deruxtecan, Sacituzumab govitecan was approved for the treatment of people with HER2-positive breast cancer, Enfortumab vedotin was approved for adult patients with locally advanced or metastatic urothelial cancer, Mirvetuximab soravtansine was approved for treatment of adults with folate receptor alpha (FRα)-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. Tumour-agnostics treatments are a new class of cancer therapies that target tumours not according to their location in the body, but by targeting a certain property of the tumour cells, called a biomarker. They are called “agnostic” because unlike typical cancer therapies, they can, in principle, fight tumours no matter where they originate. Small-molecule inhibitors have been approved to treat NTRK fusions and RET fusions and the complexity of tumour-agnostic therapies has increased with the approval of combination treatment for BRAFV600E-mutated solid tumours. Some approved drugs are larotrectinib, entrectinib and recently, repotrectinib for NTRK fusions and selpercatinib for RET fusions. The recent approval of these molecules has led to a true revolution in the treatment of solid tumors, moving from a "classic" approach based on histology to a "modern" approach based on molecular research. Nonetheless, open questions remain regarding equitable access to genomic profiling and the identification of bimarkers that predict which patients respond or not to therapy. Maintaining quality of life and managing emerging toxicities is also a key aspect.
Parasitosis represents a significant threat to farmed fish, both in freshwater and in marine aquaculture facilities. In this context, Proliferative Kidney Disease (PKD), caused by Tetracapsuloides bryosalmonae (Myxozoan: Malacosporea), is one of the main causes of mortality, showing mortality ranging from 95 to 100% in salmonid species. These parasites require two hosts to complete their life cycle: a freshwater bryozoan as the definitive host and a salmonid as the intermediate host. In the fish host, the parasites infect the gills and skin, migrate to the kidney via the vascular system, and undergo sporogenesis there. Among the principal clinical signs in the salmonid host are kidney proliferation, hepatomegaly, splenomegaly, gill anaemia, ascites, lethargy, and secondary infections, all of which are exacerbated by T. bryosalmonae replication. Due to global warming and water temperatures rising above 15°C for more months of the year, the geographic range of PKD has expanded, resulting in high mortality and economic losses for aquaculture facilities. As part of the RESILTROUT project, the present study aimed to evaluate disease spread in rainbow trout from the Piedmont region (northwest Italy) and to promote an integrated approach that correlates PKD detection with clinical signs and possible secondary bacterial infections. For this study, rainbow trout were sampled from three distinct sectors of aquaculture facilities in the Cuneo province (Piedmont, Italy) between July and December 2024. Necropsies were performed to collect spleen and kidney samples and to evaluate clinical signs associated with PKD. Parasite detection was assessed by endpoint PCR. Moreover, a bacteriological analysis of kidney samples was performed to evaluate possible coinfections. Overall, 34.43% of rainbow trout tested were positive for PKD, and 7.88% were low-level positive. The highest positivity rate was recorded in sector 2, where over 70% of animals tested were positive. The main clinical signs observed were kidney tissue proliferation, splenomegaly, and enteritis (with varying percentages across the sectors analysed). Nevertheless, most positive samples did not show macroscopic alterations. Sector 3 was the least affected by PKD, but positive samples displayed severe lesions, suggesting advanced disease or a strong immunopathological response. Bacterial coinfections were observed only in specimens from sectors 1 and 2, underscoring the immunosuppression and tissue damage caused by PKD. In conclusion, the present findings confirm the south-westward spread of PKD in the Piedmont region, highlighting the importance of an integrated diagnostic approach combining different analyses for early detection of the parasitosis. Moreover, early detection can enable the development of strategies to protect a sector particularly vulnerable to PKD outbreaks, such as the aquaculture sector.
The development of functionalized biomaterials is currently a cornerstone of regenerative medicine, aiming to bridge the gap between synthetic surfaces and biological tissues. An ideal biomaterial must be able to restore the function of damaged tissues without triggering unwanted immune responses, facilitating self-healing processes, and gradually degrading after implantation. In this context, enriching bioplastics with bioactive natural compounds represents a promising strategy for developing multifunctional medical materials capable of combining biodegradability with antimicrobial, anti-inflammatory, and regenerative properties. This innovation is particularly critical in blood-contacting environments, where red blood cells (RBCs) serve as the primary interface. As the predominant cellular component, erythrocytes play crucial biological roles. Furthermore, they act as true biochemical markers, reacting to contact with exogenous molecules through specific structural, morphological, and metabolic changes. Given the extremely delicate nature of these cells, interaction with foreign bodies can alter their functionality and trigger adverse reactions, including cell death. Therefore, prior to any clinical application, it is essential to conduct rigorous in vitro analyses to ensure full hemocompatibility, preserving the integrity of circulating RBCs. In this context, the present work aims to evaluate the hemocompatibility of bioplastics enriched with quercetin (0.5–1 mM), specifically analyzing its effects on the erythrocyte component. PVA-based bioplastics were prepared using the casting solution method and subsequently enriched with quercetin (0.5–1.0 mM). Hemocompatibility tests included the evaluation of membrane integrity (hemolysis and morphology), oxidative state (methemoglobin, determination of -SH groups, and TBARS levels), metabolic activity, and cell viability (caspase-3 activity). Our results show no evidence of erythrocyte damage in the presence of the biomaterial, but instead demonstrate a protective effect on RBCs. Specifically, a reduction in the percentage of hemolysis and improved cellular morphology were observed in RBCs in the presence of quercetin-enriched bioplastics after 2 days of incubation, compared to the control (RBCs alone or with non-enriched bioplastic). After 48 hours of incubation, analysis of the oxidative status of erythrocytes in the presence of the enriched bioplastics showed a reduction in methemoglobin, lipid peroxidation levels, and thiol group oxidation compared to the control. No changes were observed in intra/extracellular ATP levels, protein tyrosine phosphatase 1B (PTP-1B) activity, or caspase-3 activity. The results obtained pave the way for new applications for these materials, whose biocompatibility and antioxidant action are crucial in preserving the integrity and function of RBCs. However, further studies will be needed to better explore their interaction with erythrocyte metabolism and confirm their definitive clinical safety.
Species of the genus Scutellaria are known to be rich in flavonoids and phenolic compounds. Several species, particularly Scutellaria baicalensis, have been extensively studied for their antimicrobial activity against Staphylococcus aureus. However, limited information is available regarding the antimicrobial potential of Scutellaria lateriflora. In the present study, a methanolic extract of Scutellaria lateriflora was evaluated for its total phenolic and flavonoid content, antimicrobial activity against Staphylococcus aureus, and reactive oxygen species (ROS) production. Total phenolic content was determined using the Folin–Ciocalteu method with a gallic acid (GA) calibration curve (0–350 μg/mL, A = 0.0075C+0.0265, R² = 0.990). Total flavonoid content was measured using the AlCl₃ colorimetric method with a quercetin (Q) calibration curve (0–200 μg/mL, A = 0.004C+0.0004, R² = 0.989). The extract exhibited relatively low total phenolic content (6.73±0.44 mg GAE/g dry plant) but a comparatively higher flavonoid concentration (13.5 ± 0.001 mg QE/g extract), suggesting that flavonoids constitute a major proportion of the phenolic compounds present. Significant antimicrobial activity (90% the highest tested concentration) against Staphylococcus aureus was observed with MIC values around 5 μg/mL. Intracellular ROS levels did not increase compared to untreated S. aureus, suggesting maintained redox homeostasis, which may be attributed, at least in part, to the phenolic content contributing to antioxidant activity. These findings suggest that the flavonoid-rich extract of Scutellaria lateriflora exhibits notable antimicrobial activity and may represent a promising natural source of antibacterial agents maintaining the redox balance. Further studies are required to elucidate its mechanism of action and potential therapeutic applications.
