Search Results (6,507)

Hemophilias and hemoglobinopathies—including hemophilias A and B, sickle cell disease (SCD), and β-thalassemia—are debilitating genetic disorders associated with significant global health burdens. While traditional management has centered on factor replacement and transfusions, these approaches remain palliative, with limited access and durability in many regions. Recent advances in immune-based therapeutics (e.g., emicizumab, concizumab, crizanlizumab), viral vector-mediated gene addition (e.g., Roctavian, Hemgenix), and gene-modified autologous stem cell therapies (e.g., Zynteglo, Casgevy) have ushered in a new era of disease-modifying and potentially curative interventions. These therapies offer durable efficacy and improved quality of life, particularly in adult populations. However, implementation remains uneven across global health systems due to high costs, limited infrastructure, and regulatory heterogeneity. Additionally, ethical considerations such as long-term surveillance, informed consent in vulnerable populations, and social perceptions of genetic modification present ongoing challenges. Innovations such as multiplex genome editing, immune-evasive donor platforms, synthetic biology, and AI-driven treatment modeling are poised to expand therapeutic horizons. Equitable access, particularly in regions bearing the highest disease burden, will require collaborative funding strategies, regional capacity building, and inclusive regulatory frameworks. This review summarizes the current landscape of curative therapy, outlines implementation barriers, and calls for coordinated international action to ensure that transformative care reaches all affected individuals worldwide. Full article

Lactobacillus species play a fundamental role in maintaining a healthy vaginal microbiota and have been increasingly recognized for their protective effects against high-risk human papillomavirus (HR-HPV) infection and the progression of cervical intraepithelial neoplasia (CIN). These beneficial bacteria contribute to host defense through multiple mechanisms, including the production of lactic acid that sustains a low vaginal pH, enhancement of epithelial barrier integrity via E-cadherin regulation, and modulation of immune signaling pathways such as interferon responses and NF-κB activity. Lactobacillus strains exert anti-inflammatory effects by downregulating pro-inflammatory cytokines and interfering with oncogenic pathways including Wnt/β-catenin and the expression of HPV E6 and E7 proteins. Additionally, they may regulate tumor-suppressor microRNAs and modulate dendritic cell and macrophage activity, supporting antiviral immunity. Recent studies have explored their potential influence on CIN regression and HR-HPV clearance, particularly the strains Lactobacillus crispatus and L. gasseri, which are associated with favorable microbial community states. This review explores the potential mechanisms through which Lactobacillus species contribute to HR-HPV clearance and the regression of cervical dysplasia, integrating evidence from molecular studies, in vivo models, and clinical trials. The emerging role of probiotic interventions as adjunctive strategies in HPV management is also discussed, highlighting their possible synergy with conventional treatments and prophylactic vaccination. Full article

Breast cancer (BC) is the most common malignancy among Brazilian women, with a high percentage of the cases diagnosed at advanced or metastatic stages (mBC). In Brazil, where 75% of the population depends on the resource-limited public health system (SUS), mBC poses significant treatment challenges and disparities. To characterize this scenario, we conducted an online survey assessing treatment strategies available for HER2-negative, hormone receptor (HR)-positive mBC across public and private health systems. The 48-question survey addressed topics such as waiting time (WT) from oncology unit entry to treatment initiation, availability of oncologic medications, and access to palliative and multidisciplinary care teams. Between 2 August 2022 and 30 September 2022, a total of 180 oncologists were invited, and 150 met the inclusion criteria. The median WT for surgery was 60 days in the SUS versus 30 days in the private sector (p < 0.0001), and for chemotherapy, 30 days in the SUS versus 15 days privately (p < 0.0001). Endocrine therapy was the preferred first-line treatment in the SUS (83.3%), while fulvestrant was available to only 48% of respondents. Additionally, specialized palliative care teams were available according to 66% of SUS respondents compared with 82% in the private system (p = 0.001). These findings underscore persistent disparities in mBC treatment, likely driven by limited governmental health investment. Full article

Apolipoprotein A-I (apoA-I)-coated nanoemulsion particles target scavenger receptors. Adsorbed apoA-I (from the bloodstream) mediates/facilitates this targeted molecular contact, which is followed by receptor-mediated endocytosis and subsequent transcytosis of these same nanoemulsion (nanocarrier) particles across the blood–brain barrier (BBB). When the right drugs are added in advance to these high-density lipoprotein (HDL)-like nanocarriers, multifunctional combination treatment is achieved. This medication penetrates the BBB and targets particular cell-surface scavenger receptors, mainly class B type I (SR-BI). As a result, these (drug-carrying) nanoemulsions may find application in the biomedical therapy of complex medical disorders, such as dementia, as well as some aspects of aging. According to recent research, sustained inflammatory stimulation in the gut, such as via serum amyloid A (SAA), may cause the release of proinflammatory cytokines. Thus, using this “HDL-like” nanoemulsion vehicle to target drugs early (or even proactively) toward a major SAA receptor (like SR-BI), which is implicated in SAA-mediated cell-signaling processes that lead to aging and/or cognitive decline (and eventually Alzheimer’s disease or dementia), may be a useful preventive and therapeutic strategy. Full article

Obesity affects millions of individuals globally, and a deeper understanding of its associated physiological disturbances is essential for addressing key public health concerns. It has been demonstrated that the influenza virus possesses substantial global epidemic potential, with higher incidence rates observed in obese individuals and prolonged recovery times. Obese individuals exhibit impaired immune organ function, decreased immune cell activity, disrupted metabolism characterized by mitochondrial dysfunction, and an imbalance in gut microbiota associated with intestinal mucosal barrier damage. The gut microbiota and their metabolic composition in obese patients differ from those in non-obese individuals, potentially promoting viral replication and exacerbating disease severity. These factors collectively contribute to more severe tissue damage and heightened immune responses in obese patients during influenza infection. Therefore, understanding the impact of obesity on influenza virus infection dynamics enables the development of strategies promoting healthy lifestyles to manage body weight and enhance immunity against viral infections. Additionally, given that this special population may not respond optimally to antimicrobial drugs and vaccination, it is necessary to consider how treatment strategies for this group are managed. This review illustrates findings concerning the impact of obesity on the immune response to influenza virus infection, including potential underlying mechanisms. Full article

Glioblastoma (GBM) is an aggressive brain tumor characterized by an immunosuppressive tumor microenvironment (TME), which contributes to treatment resistance and disease progression. Background: Tumor-associated macrophages (TAMs), comprising both resident microglia and bone marrow–derived macrophages, play a central role in supporting tumor growth, angiogenesis, and immune evasion. Most TAMs adopt an M2-like immunosuppressive phenotype, making them a promising target for immunomodulatory strategies in GBM. Method: According to PRISMA guidelines, we conducted a systematic literature review and recruited eligible studies focused on therapeutic approaches targeting TAMs in GBM, emphasizing mechanisms of action, efficacy, and challenges. Data extraction focused on therapeutic classes, outcomes, and TAM-related biomarkers. Results: We identified 30 studies meeting the inclusion criteria. These therapies are categorized into three main strategies: inhibition of TAM recruitment, enhancement of TAM-mediated phagocytosis, and reprogramming of TAMs. Combination strategies, including TAM-targeting with checkpoint inhibitors, nanoparticles, and oncolytic viruses, show synergistic effects in preclinical models. Conclusions: Targeting TAMs represents a multifaceted strategy for GBM treatment. Current evidence underscores the need for combination approaches integrating TAM modulation with existing standard-of-care therapies. Clinical translation remains limited due to challenges such as TAM heterogeneity, plasticity, immunosuppressive therapies, and restricted drug delivery across the blood–brain barrier. Future directions should highlight personalized treatments based on detailed TME profiling. Combining TAM-targeted therapies with agents modulating metabolic or immune pathways, and leveraging advanced delivery systems and spatial transcriptomics may improve efficacy. Full article

Artesunate (AS) and tetramethylpyrazine (TMP) have been proven to have therapeutic potential in ischemic stroke. Nevertheless, their synergistic treatment mechanisms and effectiveness remain unclear. A rat MCAO model was induced, and AS, combined with TMP, was administered intranasally to rats once a day for 3 days. The neurological severity scores, TTC staining, and H&E staining were implemented to analyze tissue injuries. Evans blue staining and immunohistochemistry of ZO-1, occludin, MMP-9, and TIMP-1 were implemented to evaluate the integrity of the blood–brain barrier (BBB). ELISA was used to detect the expression levels of inflammatory factors TNF-α and IL-10. TUNEL staining and the protein expression of Bax and Bcl-2 were used to evaluate the apoptosis of brain tissue cells. The core targets were predicted by network pharmacology and verified by the OGD/R cell model and siRNA in vitro. Results showed that nasal administration of AS and TMP significantly ameliorated ischemic-stroke-induced neurological dysfunction, BBB disruption, and cortical neuronal apoptosis. The protective mechanisms mainly included adjusting the expression and ratio of tight junction proteins TIMP-1 and MMP-9 in brain tissue, regulating the HIF-1α-VEGF pathway, and anti-inflammatory effects. This study provides experimental support for the further development and application of AS and TMP nasal combinations and provides the foundation for expanding the practical-application value of artemisinin and its derivatives. Full article

Central nervous system (CNS) tumors, especially gliomas and IDH-wildtype glioblastoma, present high aggressiveness, low response to current treatments and limited survival. Several biological processes such as oxidative stress, inflammation, apoptosis, and autophagy are involved in their development. Hydroxytyrosol (HTX), a phenolic compound present in olives, has shown relevant effects on these processes in experimental models. This review analyzes its chemical characteristics, bioavailability, and ability to cross the blood–brain barrier, as well as its mechanisms of action. Despite its rapid metabolism, HTX can reach the brain in small but functional amounts, and various formulation methods can enhance its delivery to nervous tissue. HTX acts on cellular pathways such as Nrf2, NF-κB, JAK/STAT, PI3K/Akt and SIRT1, regulating redox balance, inflammation, programmed cell death, and autophagy. It can also influence gene expression through epigenetic mechanisms. In cell models, it has shown inhibitory effects on tumor growth and activation of apoptosis, without affecting non-tumor cells. These results support its possible usefulness as an adjunct in the treatment of brain tumors, although further studies in animal and human models are required. Full article

Background: Obesity and periodontitis are two chronic inflammatory diseases with a bidirectional relationship possibly mediated by microbial and immunologic signaling pathways. This narrative review aims to investigate how microbial dysbiosis and inflammation link these diseases, focusing on the interactions between the oral and gut microbiomes. Materials and methods: Peer-reviewed studies (2015–2024) from PubMed, MEDLINE, Ovid and Google Scholar were selected for their relevance to microbial dysbiosis and inflammation, prioritizing clear methodology. Non-peer-reviewed sources or studies lacking microbial/inflammatory data were excluded. Conflicting results and methodological differences, including sampling and study design, were assessed qualitatively on the basis of coherence and methodological rigor. Results: Obesity has been shown to significantly alter the composition of the oral microbiome, characterized by reduced diversity and an increased Firmicutes/Bacteroidetes ratio. At the same time, periodontal pathogens such as Porphyromonas gingivalis can invade the gut, impair barrier function and promote systemic inflammation. Both diseases share common inflammatory pathways involving adipokines and immune-system dysregulation, creating a feedback loop that exacerbates disease progression in both conditions. Obesity also appears to impair the effectiveness of conventional periodontal treatments. Conclusions: The microbial axis between the oral cavity and the gut represents a central pathway in the complex interactions between obesity and periodontitis. This relationship involves microbial dysbiosis, bacterial translocation and shared inflammatory mechanisms that collectively contribute to disease progression. Clinical relevance: A better understanding of the relationship between obesity and periodontitis supports the development of customized treatment strategies for obese patients with periodontal disease. Future research should focus on developing targeted interventions that address both conditions simultaneously to improve patient outcomes and develop more effective prevention and treatment strategies. Full article

Hospital-acquired infections (HAIs) remain a major clinical and economic burden, with pathogens such as Escherichia coli contributing to high rates of morbidity and mortality. Traditional manual disinfection methods are often insufficient, particularly in high-risk hospital environments. In this study, we investigated innovative strategies to enhance surface decontamination and reduce infection risk. First, we assessed the efficacy of the SMEG BPW1260 bedpan washer-disinfector, a thermal disinfection system for human waste containers. Our results demonstrated a reduction in Clostridium difficile and Escherichia coli contamination by >99.9% (>3 log reduction), as measured by colony-forming units (CFU) before and after treatment. Molecular techniques, including spectrophotometry, cell counting, and quantitative PCR (qPCR) for DNA quantification, confirmed reduction in bacterial contamination. Specifically, Clostridium difficile showed a reduction of approximately 89% in both optical density (OD) and cell count (cells/mL). In the case of Escherichia coli, a reduction of around 82% in OD was observed, with an even more pronounced decrease in cell count, reaching approximately 99.3%. For both bacteria, DNA quantification by qPCR was below detectable limits. Furthermore, we optimized the energy efficiency of the disinfection cycle, achieving a 45% reduction in power consumption compared to standard protocols without compromising antimicrobial efficacy. Secondly, we developed a sustainable cleaning solution based on methyl ester sulfonate surfactants derived from waste cooking oil. The detergent’s antibacterial activity was tested on contaminated surfaces and further enhanced through the incorporation of nanoassemblies composed of silver, electrostatically bound either to biomimetic magnetic nanoparticles or to conventional magnetic nanoparticles. Washing with the detergent alone effectively eliminated detectable contamination, while the addition of nanoparticles inhibited bacterial regrowth. Antimicrobial testing against E. coli revealed that the nanoparticle-enriched formulations reduced the average MIC values by approximately 50%, with MIC₅₀ values around 0.03–0.06 mg/mL and MIC₉₀ values between 0.06 and 0.12 mg/mL, indicating improved inhibitory efficacy. Finally, recognizing the infection risks associated with intra-hospital transport, we tested the SAFE-HUG Wheelchair Cover, a disposable non-woven barrier designed to reduce patient exposure to contaminated wheelchair surfaces. Use of the cover resulted in a 3.3 log reduction in surface contamination, based on viable cell counts. Optical density and bacterial DNA were undetectable in all covered samples at both 1 and 24 h, confirming the strong barrier effect. Together, these approaches—thermal no-touch disinfection, eco-friendly detergent boosted with nanoparticles, and protective transport barriers—respond to the urgent need for effective, sustainable infection control methods in healthcare settings. Our findings demonstrate the potential of these systems to counteract microbial contamination while minimizing environmental impact, offering promising solutions for the future of infection prevention in healthcare settings. Full article

Ischemic stroke triggers a dynamic immune response that influences both acute damage and long-term recovery. This review synthesizes a decade of evidence on immunological and inflammatory biomarkers in ischemic stroke, emphasizing their prognostic and therapeutic significance. Following ischemic insult, levels of pro-inflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and chemokines like interleukin-8 (IL-8) rapidly rise, promoting blood–brain barrier disruption, leukocyte infiltration, and neuronal death. Conversely, anti-inflammatory mediators such as interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) facilitate repair, neurogenesis, and immune regulation in later phases. The balance between these pathways determines outcomes and is reflected in circulating biomarkers. Composite hematological indices including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) offer accessible and cost-effective prognostic tools. Several biomarkers correlate with infarct size, neurological deterioration, and mortality, and may predict complications like hemorrhagic transformation or infection. Therapeutic strategies targeting cytokines, especially IL-1 and IL-6, have shown promise in modulating inflammation and improving outcomes. Future directions include personalized immune profiling, real-time cytokine monitoring, and combining immunotherapy with neurorestorative approaches. By integrating immune biomarkers into stroke care, clinicians may enhance risk stratification, optimize treatment timing, and identify candidates for novel interventions. This review underscores inflammation’s dual role and evolving therapeutic and prognostic relevance in ischemic stroke. Full article

Apolipoprotein A (ApoA) proteins, ApoA-I, ApoA-II, ApoA-IV, and ApoA-V, play critical roles in lipid metabolism, neuroinflammation, and blood–brain barrier integrity, making them pivotal in neurological diseases such as Alzheimer’s disease (AD), stroke, Parkinson’s disease (PD), and multiple sclerosis (MS). This review synthesizes current evidence on their structural and functional contributions to neuroprotection, highlighting their dual roles as biomarkers and therapeutic targets. ApoA-I, the most extensively studied, exhibits anti-inflammatory, antioxidant, and amyloid-clearing properties, with reduced levels associated with AD progression and cognitive decline. ApoA-II modulates HDL metabolism and stroke risk, while ApoA-IV influences neuroinflammation and amyloid processing. ApoA-V, although less explored, is implicated in stroke susceptibility through its regulation of triglycerides. Genetic polymorphisms (e.g., APOA1 rs670, APOA5 rs662799) further complicate disease risk, showing population-specific associations with stroke and neurodegeneration. Therapeutic strategies targeting ApoA proteins, including reconstituted HDL, mimetic peptides, and gene-based approaches, show promise in preclinical models but face translational challenges in human trials. Clinical trials, such as those with CSL112, highlight the need for neuro-specific optimization. Further research should prioritize human-relevant models, advanced neuroimaging techniques, and functional assays to elucidate ApoA mechanisms inside the central nervous system. The integration of genetic, lipidomic, and clinical data offers potential for enhancing precision medicine in neurological illnesses by facilitating the generation of ApoA-targeted treatments and bridging current deficiencies in disease comprehension and therapy. Full article

The peach landrace ‘Liuyefeitao’ exhibits the unique reproductive trait of self-compatibility combined with cross-incompatibility, contrasting with typical Prunus species in this way. In preliminary studies involving controlled pollination assays, we showed complete pollen tube arrest in cross-pollinated styles, whereas self-pollination enabled full tube elongation. S-genotyping identified a homozygous S₂S₂ genotype with intact S₂-RNase but a truncated PpSFB2 due to a frameshift mutation. Transcriptome profiling of the styles revealed 7937 differentially expressed genes (DEGs) between self- and cross-pollination treatments, with significant enrichment in plant MAPK signaling, plant–pathogen interactions, and plant hormone signaling transduction pathways (|Fold Change| ≥ 2, FDR < 0.01). Notably, PpSLFL3 (a pollen F-box gene) showed down-regulation in cross-pollinated styles, as validated by means of qRT-PCR. Protein interaction assays revealed direct binding between PpSLFL3 and S₂-RNase via Y2H and BiFC analysis, suggesting its role in mediating SCF complex-dependent degradation. We propose that insufficient PpSLFL3 expression during cross-pollination disrupts SCF ubiquitin ligase complex-mediated degradation of non-self S₂-RNase, leading to the toxic degradation of RNA in pollen tubes by S₂-RNase. This mechanism is mechanistically similar to unilateral reproductive barriers in Solanaceae but represents a novel regulatory module in Rosaceae. Our findings provide critical insights into the evolution of cross-incompatibility systems and molecular breeding strategies for Prunus species. Full article

Ozone pollution is a significant public health problem due to its association with chronic diseases. This study examines the effects of repeated exposure to low doses of ozone on intestinal barrier function in rats. Seventy-two male Wistar rats were divided into six groups. The control group was exposed to normal air, while the ozone groups received a dose of 0.25 ppm for four hours daily for periods of 7, 15, 30, 60, and 90 days, respectively. After treatment, the duodenum, jejunum, and colon were removed and analyzed by biochemical assays, Western blot, immunohistochemistry, and histological techniques. The results indicated an increase in oxidized lipids and structural alterations in the duodenum and jejunum after 7 days of ozone exposure. The result showed changes in haptoglobin, IL-1β, and IL-6. In addition, increased immunoreactivity varied according to intestinal structure and the duration of ozone exposure in the duodenum, jejunum, and colon. In conclusion: Ozone exposure causes an increase in proinflammatory cytokines that leads to a loss of regulation of the immune response in the duodenum, jejunum, and colon of rats, as well as structural changes that alter the intestinal barrier and perpetuate a state of chronic inflammation characteristic of inflammatory bowel diseases. Full article

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder characterized by immune dysregulation and epidermal barrier dysfunction. Advances in understanding the interplay of genetic predisposition, cytokine signaling, and environmental triggers have led to the emergence of targeted therapies. Although biologic agents such as dupilumab, tralokinumab, and lebrikizumab have revolutionized AD management, their high costs, injectable administration, and limited global accessibility highlight the need for alternative options. Small molecule therapies are gaining momentum as they target intracellular pathways central to AD pathogenesis and offer oral or topical administration routes. This review provides a comprehensive analysis of key agents including Janus kinase (JAK) inhibitors (upadacitinib, abrocitinib, baricitinib, ruxolitinib, delgocitinib), phosphodiesterase 4 (PDE4) inhibitors (crisaborole, difamilast, roflumilast, apremilast), as well as STAT6 degraders (KT621, NX3911), aryl hydrocarbon receptor modulators, histamine H4 receptor antagonists (adriforant, izuforant), and sphingosine-1-phosphate receptor modulators (etrasimod, BMS-986166). We summarize their mechanisms of action, pharmacological profiles, and pivotal clinical trial data, emphasizing their potential to address unmet therapeutic needs. Finally, we discuss safety concerns, long-term tolerability, and future directions for integrating small molecule therapies into precision treatment strategies for moderate-to-severe AD. Full article