Search Results (1,748)

Background: E-cigarette use has risen sharply among young never-smokers, largely driven by the availability of several thousand appealing flavours. This narrative review synthesises evidence on the health effects of vaping, flavour toxicology and attractiveness, designs and outcomes of flavour bans, and complementary measures. Methods: Peer-reviewed publications and institutional reports (up to January 2026) were retrieved from PubMed, Web of Science, Google Scholar, and reference lists of included articles. Evidence from about 200 references was synthesised by a multidisciplinary working group. Results: Although flavouring substances are generally considered safe for ingestion, their inhalation toxicity remains uncertain. In vitro and in vivo studies have reported oxidative stress, inflammation, cytotoxicity, impaired ciliary function, transcriptomic changes, genotoxicity, and DNA damage. These findings—along with the strong youth appeal of fruit/sweet flavours, the inconclusive effects of flavours on smoking cessation, and persisting uncertainties—support banning non-tobacco e-cigarette flavours under the precautionary principle. Flavour bans can reduce e-cigarette use and initiation, especially among young adults, although partial substitution towards combustible cigarettes has been reported in some U.S. states. Policy success requires effective enforcement, prevention of industry circumvention, curbing cross-border sales, and closing regulatory loopholes—ideally at the international level (e.g., EU-wide). Conclusions: E-cigarette flavours may increase vaping toxicity and strongly appeal to youth, justifying flavour bans to prioritise youth protection. To maximise effectiveness, accompanying measures and sustained investment in tobacco prevention, youth education, and accessible evidence-based smoking cessation support are essential. Full article

Background/Objectives: Lifestyle behaviors such as smoking, vaping, and physical activity can induce epigenetic modifications that influence health trajectories and may provide forensic value. DNA methylation signatures linked to these behaviors offer potential for behavioral inference, personalized health assessment, and improved investigative practices. This study aimed to characterize methylation patterns associated with nicotine exposure and exercise using buccal cell DNA profiling, and to evaluate the extent to which these patterns differentiate harmful and protective lifestyle habits. Methods: Buccal epithelial DNA was analyzed using the Illumina Infinium MethylationEPIC v2 BeadChip to assess genome-wide methylation. Participants were categorized by smoking status, vaping behavior, and exercise activity. Differentially methylated regions (DMRs) and CpG sites were identified through pairwise comparisons among smokers, vapers, non-smokers/non-vapers, athletes, and sedentary individuals. A threshold of p < 1 × 10⁻⁴ was applied for significant differentially methylated CpG sites. Results: Distinct epigenetic profiles were associated with smoking/vaping and physical activity. Five DMRs differentiated smokers from non-smokers/non vapers, while 11 DMRs distinguished vapers from the same reference group. Twenty-eight DMRs displayed divergent methylation patterns between smokers and vapers. Exercise also showed measurable epigenetic influence: control athletes exhibited 26 significantly differentially methylated CpG sites relative to non-athletes, and smoker athletes demonstrated 126 suggestive differential sites compared to sedentary smokers. Additionally, 63 sites differentiated smoker athletes from non-smoker/non-vaper non-athletes, indicating interactions between risk-associated and health-promoting behaviors. Conclusions: Buccal cell DNA methylation profiling effectively captured signatures associated with smoking, vaping, and physical activity. These findings underscore the potential of epigenetic markers for lifestyle assessment in both personalized medicine and forensic investigations. Full article

Cadmium (Cd) is an environmental toxicant originating from both natural processes and human activities. Cd has been strongly associated with multiple diseases, including breast cancer (BC). Background/Objective: Environmental Cd exposure represents a significant contributor to BC onset and progression. Cd-induced breast carcinogenesis is driven by a constellation of molecular events, including DNA damage, oxidative stress (OS), and the dysregulation of key signaling pathways. These include the ERK/JNK/p38 MAPK cascade, the PI3K/AKT/mTOR axis, NF κB activation, and Wnt signaling, all of which collectively promote tumor initiation, survival, and metastasis. This review underscores the complex interplay between Cd exposure and its effects on cancer-triggering factors. Methods: The complexity of the mechanisms Cd-induced BC, underlying Cd-induced BC makes it challenging to treat, highlighting the need for novel therapeutic strategies that complement or enhance conventional chemotherapy. Therefore, this review was developed by reviewing the literature and presenting the different aspects of the challenge associated with Cd exposure and BC therapy. Results: Phytochemicals, especially phenolics, alkaloids, carotenoids, terpenoids, and related plant-derived compounds, have emerged as promising candidates for mitigating Cd-induced BC. Their antioxidants, anti-estrogenic, and anti-inflammatory properties position them as potential chemopreventive and therapeutic agents capable of counteracting Cd’s molecular toxicity. Conclusions: The review presents current evidence linking Cd exposure to BC development and highlights the protective potential of selected phytochemicals in preventing or attenuating Cd-induced BC. Understanding these interactions reinforces the importance of phytochemical-based interventions as a strategy to reduce Cd-related cancer risk and support breast health. Full article

The etiology of autism spectrum disorder (ASD) implicates genetic predispositions and environmental chemicals, such as polybrominated diphenyl ethers (PBDEs). We aimed to identify whether mitochondrial quality control (MQC) was involved in ASD-relevant behavioral changes induced by decabromodiphenyl ether (deca-BDE, BDE-209) and the alleviation by melatonin. Pregnant rats exposed to BDE-209 (50 mg/kg i.g.) were administrated melatonin through drinking water (0.2 mg/mL) during gestation and lactation. Behavioral assessments integrated open-field test, three-chamber social test, and Morris water maze; mitochondrial detections took transmission electron microscopy, immunofluorescence, and homeostasis together; hippocampal molecular network was identified through transcriptomics profiles, combining dendritic morphology analysis after Golgi-Cox staining. Melatonin supplementation attenuated BDE-209-reduced social and cognitive ability, accompanied by improvements in hippocampal synaptic plasticity (dendritic spines, PSD95, SNAP25). Mitochondrial dysfunctions, shown as decreases in complex IV activity, ATP content, and mtDNA copies, plus redox imbalance (ROS/SOD2) and resultant mitochondrial membrane potential disruption and apoptosis, together with fusion/fission dynamic (MFN2/DRP1), biogenesis (SIRT1-PGC1α-TFAM), and mitophagy (SIRT3-FOXO3-PINK1) suppression, were reversed by melatonin partially through SIRT1 (Sirtuin-1)-dependent pathways, as these protections were abolished by inhibitor EX527. This study highlighted the SIRT1–SIRT3 axis in MQC and behavioral effects, providing novel intervention for PBDEs’ neurodevelopmental impairment. Full article

Leishmaniases are infections caused by Leishmania parasites and transmitted through the bite of infected female Phlebotomus (Old World) and Lutzomyia (New World) sandflies. The disease disproportionately affects marginalized communities with limited healthcare access. With no approved human vaccines available, leishmaniasis treatment and prevention depend heavily on chemotherapeutics that face growing drug resistance challenges alongside toxicity concerns. The development of safe, effective and affordable vaccines against human leishmaniasis remains a global health priority for disease control and elimination, mostly in resource-limited settings. This review synthesizes progress in leishmaniasis vaccine platforms including live-attenuated parasites, whole-killed parasites, DNA, protein subunit, peptide-based and chimeric/multiepitope vaccines and their homogenous and heterogenous efficacy. Live-attenuated and whole-parasite vaccines have been accounted to elicit robust cellular immunity but pose safety risks, particularly in immunocompromised hosts. While both second- and third-generation vaccines exemplified by LEISH-F1/F3 polyproteins, elicit strong Th1-biased T cell responses in preclinical models, their efficacy in humans remains limited. However, the highlighted collective efforts are pivotal in steering the rational development of future research using various formulations for multiple management of leishmaniasis through cross-protection. Furthermore, emerging strategies including mRNA platforms, nanoparticle delivery, reverse vaccinology, and immunoinformatics offer promising avenues for accelerating vaccine discovery and advancing the development of novel and effective human vaccines. Full article

African swine fever (ASF), a highly contagious and lethal viral disease caused by the African swine fever virus (ASFV), poses a severe threat to the global swine industry. Recent outbreaks across Asia, Europe, and the Caribbean are exacerbating the challenge. Current control measures rely mainly on early detection, culling and strict biosecurity practices, underscoring the urgent need for a safe and effective vaccine. Since the mid-1960s, diverse vaccine strategies, including inactivated, subunit, DNA/mRNA, vectored, and live attenuated virus (LAV) vaccines, have been explored. Inactivated vaccines have consistently failed to confer protection due to insufficient functional antigen presentation and weak cellular immune activation. Subunit vaccines targeting single or multiple ASFV antigens have also shown limited success, often failing to induce sterile or long-lasting immunity. Among these approaches, LAV vaccines have demonstrated the greatest promise in eliciting robust and durable immune responses. However, major knowledge gaps remain regarding ASFV biology, ASFV–host interactions, ASFV immune evasion mechanisms, protective and cross-protective immunity, stable cell lines for LAV production, virulence reversion of LAVs, and the lack of harmonized standards for evaluating vaccine safety and efficacy, all of which impede the development of safe and broadly effective ASF vaccines. This narrative review summarizes recent advances in ASF vaccine research and highlights the critical obstacles that must be overcome to achieve successful ASF vaccine development. Full article

Background/Objectives: The gut–brain axis is increasingly recognized as a critical modulator of cognitive function. This study investigated the neurotoxic effects of combined exposure to bacterial lipopolysaccharide (LPS) and the antiretroviral drug zidovudine (ZDV) in a mouse model, and evaluated the protective potential of two probiotic interventions: Bacillus subtilis and a mixture of lactobacilli. Methods: Cognitive function was assessed using the Morris water maze (MWM). Gut microbiota composition was analyzed by 16S rRNA sequencing, and intestinal morphology was examined histologically. Gene expression of neuroinflammatory markers and mitophagy-related genes in brain tissue was quantified by RT-PCR. Plasma levels of cell-free mitochondrial DNA (cf-mtDNA) were measured as a marker of mitochondrial damage. Results: Combined LPS + ZDV exposure induced systemic inflammation, impaired spatial memory, damaged the intestinal mucosa, and caused dysbiosis characterized by an increase in pro-inflammatory Muribaculaceae. In the brain, LPS + ZDV significantly upregulated Tnfa expression, confirming neuroinflammation. Bacillus subtilis administration prevented cognitive deficits, maintained Tnfa at control levels, and significantly reduced Il1b and Il6 expression compared to the LPS + ZDV group. This was accompanied by activation of the PINK1/PTEN-dependent mitophagy pathway, prevention of cf-mtDNA release, and restoration of gut microbial diversity. In contrast, the Lactobacilli mixture not only failed to improve outcomes but was associated with exacerbated intestinal damage, more pronounced cognitive dysfunction, and no reduction in neuroinflammatory markers. Conclusions: Combined exposure to LPS and ZDV induces gut–brain axis dysfunction characterized by neuroinflammation, cognitive impairment, intestinal damage, and dysbiosis. Bacillus subtilis effectively preserves cognitive function through activation of PINK1/PTEN-dependent mitophagy and suppression of neuroinflammation, highlighting its potential as a therapeutic candidate for cognitive impairments associated with gut–brain axis dysfunction. The contrasting effects of the lactobacilli mixture underscore the critical importance of strain-specificity in probiotic interventions. Full article

Aging is closely associated with oxidative stress, which contributes to functional decline and increased vulnerability to neurodegenerative diseases. Natural antioxidants, such as Chlorella Growth Factor (CGF) and γ-polyglutamic acid (γ-PGA), possess antioxidant and anti-aging properties; however, their combined effects remain unknown. This study investigated the potential synergistic effects of CGF and γ-PGA supplementation in senescence-accelerated mouse-prone 8 (SAMP8) mice, a model characterized by early cognitive decline, locomotor deficits, and elevated oxidative DNA damage. Three-month-old male SAMP8 mice (n = 40) were divided into four groups: control, CGF (49.2 mg/kg BW/day), γ-PGA (20.5 mg/kg BW/day), and combined CGF + γ-PGA (69.7 mg/kg BW/day), and were treated for 13 weeks. Behavioral and physiological assessments included locomotor activity, aging index, and cognitive function (passive and active avoidance tests). Biochemical analysis focused on brain 8-hydroxy-2′-deoxyguanosine (8-OHDG) as a biomarker of oxidative DNA damage. Supplementation with CGF and γ-PGA, particularly in combination, significantly improved locomotor activity, aging scores, and cognitive functions. Notably, the combined treatment yielded the greatest reduction in brain 8-OHDG levels. These findings indicate that CGF and γ-PGA, when administered together, exert enhanced protective effects against functional and molecular aging. In conclusion, long-term supplementation with CGF and γ-PGA protects against aging-related decline in SAMP8 mice. This study highlights the potential of CGF and γ-PGA as safe, natural candidates for the development of functional foods or nutraceuticals aimed at promoting healthy aging and reducing oxidative stress-associated disorders. Full article

Background: The combination of conventional drugs and inhibitors of signaling molecules is an effective strategy to increase cancer treatment efficacy and reduce drug doses to protect against their cytotoxic effects. Our research has shown the cisplatin concentration-dependent shift in the role of MAP kinase JNK from antiapoptotic to proapoptotic in non-small cell lung cancer A549 cells. Cell death/survival signaling molecules, tumor suppressor p53 and pro-survival protein kinase AKT were detected to be differently regulated by JNK inhibition at low vs. high cisplatin concentrations. Here, we further investigated the phenomenon and potential mechanisms of combined JNK inhibition and cisplatin treatment. Methods: Cell death in vitro was evaluated by MTT and Western blot assays after combined cisplatin and specific inhibitor treatment; two-way ANOVA was used for analysis. Results: JNK is differently involved in determining cellular sensitivity to different DNA-damaging drugs. There is no universal cell death induction mechanism originating from DNA damage through the involvement of JNK. The outcome of JNK inhibition also depends on the cell type. We found that there is an unusual reciprocal interaction between p53 and AKT in cisplatin-treated A549 cells, where p53 inhibits AKT, while AKT activates p53. In the case of cisplatin + JNK inhibitor SP600125, DNA damage and reactive oxygen species (ROS) contribute to cell death regulation in different ways. ROS exert opposite roles on cell fate-determining molecules p53 and AKT, and ROS act on p53 and AKT in opposite directions at low vs. high concentrations of cisplatin, combined or not with JNK inhibition. The differentially activated p53 in response to ROS (at low versus high concentrations of cisplatin, combined with JNK inhibitor) may be a molecular switch in the role of JNK from antiapoptotic to neutral/proapoptotic, and an executor of cell death. ROS is a possible threshold regulator that, together with an as-yet-unidentified factor, can differentially regulate p53. As a result, AKT phosphorylation and function are altered. The findings emphasize the importance of assessing the role of drug concentration when combining them with JNK inhibition when monitoring therapeutic efficacy and toxicity issues in personalized cancer treatment. Full article

Garlic (Allium sativum L.) cultivars in Korea, particularly the widely adaptable ‘Hongsan’, are challenging to identify in processed forms or seedlings due to the plasticity of phenotypic traits such as clove tip greening. This uncertainty increases the risk of mislabeling and the infringement of breeders’ rights under the UPOV framework. This study aimed to develop a stable SCAR marker for ‘Hongsan’-specific identification using a RAPD-based DNA pooling method. Sixty Operon primers (>60% GC) were screened against ‘Hongsan’ gDNA versus a multi-cultivar DNA pool (‘Daeseo’, ‘Uiseong’, ‘Danyang’, and ‘Namdo’); OPE-01 consistently amplified a unique 1.3 kb band, which was cloned and sequenced, revealing a 1272 bp sequence with a translocation junction (878 + 394 bp), a 18 bp insertion, and an EcoRI site on chromosome 2 (NCBI reference sequence: GCA_030737875.1). SCAR primers SaH191R/SaH513F produced a specific 545 bp amplicon in Hongsan, clearly distinguishing it from other cultivars and parental lines, indicating that the marker locus is related to the paternal line ‘9209’. This RAPD-to-SCAR marker overcomes reproducibility limitations and enables reliable authentication of Hongsan in processing powders and black garlic irrespective of environmental factors. This cost-effective and rapid assay ensures industry transparency, quality control, and IP protection for Korean garlic production. Full article

Triple-negative breast cancer (TNBC) represents 10–20% of breast cancers and is characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, leaving cytotoxic chemotherapy as the main systemic treatment. However, rapid development of resistance, via drug efflux, enhanced DNA repair, apoptosis evasion, epithelial-to-mesenchymal transition, and tumor microenvironment protection, limit long-term efficacy. Small interfering RNA (siRNA) therapeutics can silence key resistance drivers, but their clinical potential is hindered by instability, poor biodistribution, and off-target effects. Nanocarrier-based delivery systems offer solutions by protecting siRNA, enhancing tumor accumulation, enabling targeted intracellular release, and permitting co-delivery with chemotherapeutics for synergistic effects. We conducted a narrative review in PubMed from database inception to August 2025. The included studies demonstrated that lipid, polymeric, inorganic, and hybrid nanocarriers can achieve efficient target knockdown, reverse drug resistance mechanisms, and significantly enhance antitumor responses in resistant TNBC models. Several platforms also reduced metastatic spread and improved survival in vivo. While preclinical results are compelling, clinical translation remains limited by incomplete safety profiling and heterogeneity in delivery efficiency. This review synthesizes mechanistic insights and delivery innovations, outlining a roadmap for translating siRNA-loaded nanocarriers into effective therapies for chemoresistant TNBC. Full article

Background/Objectives: The primary mechanisms driving UV-induced carcinogenesis include DNA damage leading to mutations, and reactive oxygen species (ROS) formation that can cause inflammation, immunosuppression, alteration of the structure of proteins, including transcription factors, and carcinogenesis through epigenetic modifications. Curcumin has the potential to inhibit DNA-methyltransferases (DNMTs) and histone deacetylases (HDACs), but this has not been examined yet at the gene-expression level. In this article, we aimed to explore the potential protective effect of curcumin against UV radiation-induced DNMT1, DNMT3A, DNMT3B, HDAC5, and HDAC6 expression in immortalized keratinocytes (HaCaT), hepatocellular carcinoma (HepG2), and lung adenocarcinoma (A549) cells. Methods: Cells were exposed to UV-B radiation for different periods and treated with curcumin at different concentrations to evaluate dose-related trends in DNMT and HDAC gene expression compared with untreated UV-exposed cells. Results: UV exposure increased the DNMT and HDAC gene expression levels in the examined cells dose-dependently. Curcumin exposure resulted in decreased mRNA expression levels of DNMT and HDAC gene expression. In our experimental setup curcumin modulated the transcription of DNMT and HDAC genes in A549 and HaCaT cells in a dose-dependent manner. In HepG2 cells, UV-B induced a less pronounced, but still significant, increase in the examined gene expression levels. This effect was also dose-dependently decreased by curcumin, although less markedly. Conclusions: Future studies are warranted to examine if curcumin combined with other chemopreventive agents through the HDAC and DNMT inhibitory activity at the gene expression level can exert a synergistic effect and may potentially supplement cancer therapeutic strategies. Full article

Single nucleotide polymorphisms (SNPs), as common genetic variations, can influence biological processes. Identifying these variations is crucial for recognizing high-risk subgroups, guiding preventive strategies, and enabling personalized management. Objective: This study aimed to determine the relationship between SNPs and survival, thereby identifying genetic profiles associated with increased risk. Methods: We included seropositive patients with Chagas disease who had a disease duration of >20 years and no comorbidities. DNA was extracted. A SNP panel focusing on genes involved in cardiac structure was created from the GnomAD database. Patients were followed for 8 years to assess survival. The association between SNPs and survival was evaluated, and a genetic risk score was generated. Univariate and multivariate Cox regression models assessed the association between SNPs (coded as ordinal variables) and survival time. SNPs with p < 0.05 were selected to construct a risk score, which was then assessed using Kaplan–Meier curves and median survival times. Results: A total of 182 patients were included, with 96.7% completing follow-up for a median of 5.1 years (interquartile range: 3.4–6.5). The median age was 62 years; 39.6% of patients were male, and 31% had reduced left ventricular ejection fraction. Univariate analysis showed that 3 of the 68 SNPs studied were associated with survival. Variant rs3755863 (PPARGC1A gene) was significantly associated with an increased risk of death (hazard ratio, HR = 1.94; p = 0.022). Conversely, two variants, rs7310615 (SH2B3 gene) and rs7405731 (JUP gene), showed a protective effect with significantly reduced mortality risk (HR = 0.45; p = 0.006 and HR = 0.48; p = 0.006, respectively). In multivariate analysis, rs7310615 and rs7405731 remained significantly associated with survival. A genetic risk score was constructed, assigning 0 points for homozygous wild-type, 1 point for heterozygotes, and 2 points for homozygous alternative alleles. Individual scores were calculated, and survival was estimated for each score category using Kaplan–Meier analysis and median survival times. Conclusions: Two SNPs were identified as significantly associated with survival. These findings require confirmation in larger and more diverse populations. Their validation could enable the identification of a subgroup of patients at particularly high risk. Full article

Background/Objectives: Habitat degradation and fragmentation reduce population size, genetic diversity, and connectivity, increasing extinction risk in small and isolated populations. Coastal wetlands of northwestern Peru have undergone extensive anthropogenic modification, yet the genetic and ecological status of resident carnivore populations remains poorly documented. This study aimed to assess genetic diversity, relatedness, demographic signals, and diet composition of a Pampas cat (Leopardus garleppi) population inhabiting the Mangroves San Pedro de Vice (MSPV), a Ramsar-listed coastal wetland. Methods: We combined noninvasive fecal genotyping using eight nuclear microsatellite loci with vertebrate DNA metabarcoding. Scat samples were collected across three field seasons (2019–2021). Individual identification, genetic diversity metrics, genetic mark–recapture estimation of census size (Nc), effective population size (Ne), bottleneck tests, and relatedness analyses were performed to evaluate population status and kin structure. Dietary composition was characterized using metabarcoding and assessed for sex-specific differences. Results: Sixty-eight scats yielded multilocus genotypes for nine individuals (six males, three females). Genetic analyses revealed moderate diversity (mean allelic richness = 3.47; observed heterozygosity = 0.69; expected heterozygosity = 0.58) and evidence consistent with a recent genetic bottleneck. Genetic mark–recapture analyses estimated a small census size (Nc = 9; 95% CI: 7.0–9.0), while the effective population size was markedly low (Ne = 2.4; 95% CI: 1.5–7.4), yielding an Ne/Nc ratio of ~0.27. Multiple first-order kin dyads were detected, indicating strong local kin structure and limited external recruitment. Metabarcoding identified eight vertebrate prey species, with diet dominated by the native rodent Aegialomys xanthaeolus. No significant sex-specific differences in diet composition were detected. Conclusions: The MSPV Pampas cat population represents a small, kin-structured range-edge population showing signatures consistent with recent genetic erosion and restricted connectivity. These patterns align with isolation in a degraded coastal wetland landscape, highlighting the importance of habitat protection, prey resource conservation, and restoration of functional connectivity to support long-term population persistence. Full article

Glutathione (GSH) is a central regulator of redox homeostasis, melanogenesis, and cellular repair, and has gained increasing attention in dermatology for its potential roles in skin brightening, anti-aging, and tissue regeneration. This systematic review evaluated molecular, clinical, and translational evidence of glutathione’s applications and safety across different delivery modalities. The review followed PRISMA guidelines and included studies published between 2000 and 2025. A total of 194 studies met the inclusion criteria, evaluating the effectiveness of glutathione in esthetic dermatology and regenerative medicine. Topical and oral glutathione demonstrated favorable effects on pigmentation, skin brightness, hydration, and oxidative stress markers. Injectable glutathione increases systemic levels rapidly, but is associated with short-lasting effects and potential safety concerns. Glutathione S-transferases facilitate the conjugation of glutathione to electrophilic xenobiotics, thereby protecting proteins and nucleic acids from electrophile-induced damage. Glutathione Peroxidase employs GSH as an electron donor to reduce hydrogen peroxide and lipid hydroperoxides, thus protecting membrane lipids, mitochondrial membranes, and DNA from oxidative damage. Glutathione facilitates the regeneration of other antioxidants, such as vitamin C and vitamin E, through redox cycling. A consistent correlation exists between reduced GSH levels and neuronal dysfunction. Elevated GSH levels enhance cellular resistance to oxidative stress and reduce apoptotic signaling. GSH plays a pivotal role in cutaneous aging and tissue repair through redox regulation, mitochondrial protection, and the modulation of inflammatory and extracellular matrix pathways. To elucidate the clinical significance of glutathione, future research should focus on conducting randomized controlled trials, developing standardized formulations, and performing long-term safety assessments. Full article