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Keywords = toxicity index

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21 pages, 3501 KB  
Article
Transferosomes Containing 20-Hydroxyecdysone for Psoriasis Treatment: Preparation, Characterization, and In Vitro and In Vivo Toxicity Assessment
by Pawel Bakun, Dariusz T. Mlynarczyk, Kacper Durowicz, Szymon Tomczak, Jolanta Dlugaszewska, Daniel Ziental, Robert Kleszcz, Aleksandra Majchrzak-Celińska, Ewelina Musielak, Mateusz de Mezer, Mikołaj Baranowski, Aneta Wozniak-Braszak, Emilia Cicha, Violetta Krajka-Kuzniak, Anna Jelinska, Tomasz Goslinski and Ludwika Piwowarczyk
Pharmaceuticals 2026, 19(8), 1157; https://doi.org/10.3390/ph19081157 (registering DOI) - 25 Jul 2026
Abstract
Background/Objectives: Psoriasis is a chronic, immune-mediated inflammatory skin disorder affecting millions of individuals worldwide. It remains a therapeutic challenge due to the limited skin penetration of many drugs, adverse systemic effects, and the need for long-term management. Transferosomal nanoformulations containing natural products [...] Read more.
Background/Objectives: Psoriasis is a chronic, immune-mediated inflammatory skin disorder affecting millions of individuals worldwide. It remains a therapeutic challenge due to the limited skin penetration of many drugs, adverse systemic effects, and the need for long-term management. Transferosomal nanoformulations containing natural products were proposed as a potential therapeutic tool. Methods: Transferosomes containing 20-hydroxyecdysone and resveratrol were prepared using the thin-film hydration method followed by probe ultrasonication, generating several formulation variants differing in composition. The vesicles were characterized by dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) to determine size, polydispersity index (PDI), and zeta potential. Furthermore, time-domain nuclear magnetic resonance (TD-NMR) relaxation measurements were employed to evaluate local molecular dynamics and membrane fluidity, providing deeper insights into the structural integrity and elasticity of the transferosomal systems. The stability of the nanoformulations was assessed for one month in water and phosphate-buffered saline (PBS). Viability was evaluated in vitro using the MTS assay on human epidermal keratinocyte (HEK) and psoriasis-patient derived human epidermal keratinocyte (PHEK) cell lines, alongside antimicrobial profiling against four representative human skin microbiome strains. Acute toxicity was further examined in vivo using the Danio rerio FET test. Results: The formulations demonstrated high physicochemical stability over the tested period, maintained desirable particle sizes within 100–200 nm, and showed no cytotoxicity toward skin-associated bacteria or in the zebrafish model. Conclusions: The developed nanoformulations present suitable properties in terms of safety and stability and can be considered for potential use in psoriasis treatment. Full article
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20 pages, 2699 KB  
Article
Human Health Risks Associated with the Consumption of Wild Foods and Geophagic Material Along the Great Dyke and Surrounding Areas in Zimbabwe
by Aaron Chigona, Farai Mapanda, Chakare Benhura, Justice Nyamangara, Phillip Nyamugafata, Menas Wuta, Ntandokamlimu Nondo, Sessely Mavunga and Takudzwa Nota
Int. J. Environ. Res. Public Health 2026, 23(8), 957; https://doi.org/10.3390/ijerph23080957 (registering DOI) - 24 Jul 2026
Abstract
Background: Wild foods and geophagic material are important in the nutrition of communities along Zimbabwe’s Great Dyke, a serpentinic ultramafic (SUG) and surrounding granitic geological (GG) environment. However, the health risks associated with consumption of these in terms of toxic geogenic contaminants (TGC) [...] Read more.
Background: Wild foods and geophagic material are important in the nutrition of communities along Zimbabwe’s Great Dyke, a serpentinic ultramafic (SUG) and surrounding granitic geological (GG) environment. However, the health risks associated with consumption of these in terms of toxic geogenic contaminants (TGC) is largely unknown. The study objective was to evaluate the health risks associated with consuming wild foods and geophagic materials from these environments. Methods: Health risk assessments were determined using the hazard quotient, hazard index (HI) and life cancer risk (LCR) for 10 TGCs in wild foods and geophagic material. Results: High human health risks (HI ≥ 1) were found in six wild foods and geophagic material under the SUG environment compared with five wild foods and geophagic material under the GG environment. Wild foods and geophagic materials exceeded the tolerable risk level of 1 × 10−4. Their LCR values ranged from 2.11 × 10−1 to 6.83 × 10−7. All TGCs had high LCR values above the tolerable risk level, except for Cu, Fe, Mn and Zn. Conclusions: Infusion reduced the LCR values for TGCs, with only Pb in the GG environment decreasing to below tolerable risk level. Communities should apply selective consumption and avoid F. sycomorus and geophagic materials with cancer risks. Full article
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19 pages, 3214 KB  
Article
The Host Tissue Repair Vulnerability Index (HTRVI): A Composite Biomarker for Predicting Osteoradionecrosis in Locally Advanced Nasopharyngeal Carcinoma
by Efsun Somay, Erkan Topkan, Sibel Bascil and Ugur Selek
Med. Sci. 2026, 14(4), 427; https://doi.org/10.3390/medsci14040427 (registering DOI) - 24 Jul 2026
Abstract
Background: Osteoradionecrosis of the jaw (ORNJ) remains a major late complication of head and neck radiotherapy, and risk assessment relies mainly on clinical and dosimetric factors. We constructed the Host Tissue Repair Vulnerability Index (HTRVI), a composite biomarker integrating inflammatory, immune-nutritional, and oxygenation-related [...] Read more.
Background: Osteoradionecrosis of the jaw (ORNJ) remains a major late complication of head and neck radiotherapy, and risk assessment relies mainly on clinical and dosimetric factors. We constructed the Host Tissue Repair Vulnerability Index (HTRVI), a composite biomarker integrating inflammatory, immune-nutritional, and oxygenation-related parameters, to estimate biological susceptibility to ORNJ in locally advanced nasopharyngeal carcinoma (LA-NPC). Methods: This retrospective cohort included 261 LA-NPC patients treated with definitive concurrent chemoradiotherapy between 2010 and 2021. HTRVI was calculated as (CRP × platelet × neutrophil)/(albumin × lymphocyte × hemoglobin). HTRVI was compared with hemoglobin (Hb) and the Global Immune-Nutrition-Inflammation Index (GINI) using receiver operating characteristic analysis. Multivariable logistic regression, restricted cubic spline analysis (RCS), and bootstrap resampling assessed independent association, continuous risk relationship, and internal validation. Results: During a median follow-up of 63.8 months, 24 patients (9.2%) developed ORNJ. HTRVI showed superior discrimination (AUC, 0.864; 95% CI, 0.769–0.932) compared with Hb (AUC, 0.785; p = 0.001) and GINI (AUC, 0.759; p = 0.045). HTRVI remained independently associated with ORNJ after adjustment for mandibular mean dose and post-CCRT tooth extraction burden (OR per standard deviation increase, 4.81; 95% CI, 1.10–20.99; p = 0.037). RCS analysis showed a significant continuous association between HTRVI and ORNJ risk (Poverall < 0.001) without nonlinearity (Pnonlinear = 0.736). Internal validation showed minimal optimism (bootstrap-corrected AUC, 0.993). Conclusions: HTRVI was independently associated with ORNJ and provided additional predictive information beyond established clinical and dosimetric factors in this single-center cohort. The continuous HTRVI–ORNJ association supports a biological continuum model of host tissue repair vulnerability. However, HTRVI should currently be regarded as an investigational biomarker requiring independent external and prospective validation before clinical implementation. Full article
(This article belongs to the Special Issue Insights into the Modern Landscape of Cancer Therapeutics)
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26 pages, 24082 KB  
Article
Thymoquinone Potentiates Docetaxel-Induced Antitumor Activity with the Involvement of ROS and PI3K/AKT Pathway Modulation in Triple-Negative Breast Cancer Cells
by Aylin Orhaner, Mehmet Cudi Tuncer and İlhan Özdemir
Pharmaceuticals 2026, 19(8), 1154; https://doi.org/10.3390/ph19081154 (registering DOI) - 24 Jul 2026
Abstract
Background: Drug resistance and treatment-associated toxicity remain major limitations of conventional chemotherapy for triple-negative breast cancer (TNBC). Thymoquinone (TQ), a bioactive phytochemical derived from Nigella sativa, has demonstrated anticancer properties and may enhance the therapeutic efficacy of docetaxel (DTX) through complementary [...] Read more.
Background: Drug resistance and treatment-associated toxicity remain major limitations of conventional chemotherapy for triple-negative breast cancer (TNBC). Thymoquinone (TQ), a bioactive phytochemical derived from Nigella sativa, has demonstrated anticancer properties and may enhance the therapeutic efficacy of docetaxel (DTX) through complementary molecular mechanisms. Objective: To investigate whether TQ potentiates the antitumor activity of DTX in MDA-MB-231 TNBC cells by affecting apoptosis, oxidative stress, wound closure, and PI3K/AKT pathway-related gene expression. Methods: MDA-MB-231 TNBC cells and HaCaT keratinocytes were treated with TQ, DTX, or their combination. Cell viability was determined using the MTT assay, and drug interactions were evaluated by the Chou–Talalay combination index (CI) method. Apoptosis, intracellular reactive oxygen species (ROS) production, ROS rescue experiments using N-acetyl-L-cysteine (NAC), caspase-9 expression, wound closure, and gene-expression changes were assessed using Annexin V/PI flow cytometry, DCFH-DA-based flow cytometric and fluorescence analyses, immunocytochemistry, wound-healing assay, and quantitative real-time PCR (qRT-PCR), respectively. Bioinformatic analyses were performed to identify signaling pathways associated with the observed molecular alterations. Results: The TQ + DTX combination demonstrated synergistic cytotoxicity and significantly increased apoptotic cell death compared with either monotherapy. Combination treatment markedly enhanced intracellular ROS accumulation, whereas NAC pretreatment significantly attenuated ROS generation and partially reversed the cytotoxic and pro-apoptotic effects, suggesting the involvement of ROS in the observed antitumor effects. Caspase-9 immunoreactivity was markedly increased following combination treatment, suggesting the involvement of the intrinsic apoptotic pathway. Furthermore, the combination significantly suppressed wound closure and downregulated BCL2, PIK3CA, and AKT1 while upregulating BAX, CASP9, and PTEN. Bioinformatic analyses identified apoptosis, p53, PI3K/AKT, mTOR, and MAPK signaling as the principal pathways potentially associated with the observed gene expression changes. Conclusions: TQ potentiates the antitumor activity of DTX, with the involvement of oxidative stress, apoptotic signaling, suppression of wound closure, and regulation of PI3K/AKT pathway-related gene expression in TNBC cells. These findings provide evidence supporting further preclinical investigation of the TQ + DTX combination as a promising therapeutic strategy for triple-negative breast cancer. Full article
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23 pages, 2870 KB  
Article
Comparative Mineral Profile and Safety Assessment of Arctic Storm-Cast Macroalgae: Implications for Human Health Risk Evaluation
by Ekaterina D. Obluchinskaya, Olga N. Pozharitskaya, Anna V. Daurtseva and Alexander N. Shikov
Appl. Sci. 2026, 16(15), 7417; https://doi.org/10.3390/app16157417 - 24 Jul 2026
Abstract
Storm-cast macroalgae represent a vast, underutilized biomass in the Arctic. This study evaluates the mineral composition, safety, and nutritional potential of storm-cast versus attached macroalgae from the Barents and White Seas to determine their suitability for commercial application. Mineral profiles (K, Na, Ca, [...] Read more.
Storm-cast macroalgae represent a vast, underutilized biomass in the Arctic. This study evaluates the mineral composition, safety, and nutritional potential of storm-cast versus attached macroalgae from the Barents and White Seas to determine their suitability for commercial application. Mineral profiles (K, Na, Ca, Mg, As, Zn, Fe, Cu, Hg, Pb, and Cd) were determined by atomic absorption spectroscopy (AAS), while iodine (I) was analysed via iodometric titration. All elemental data were subsequently evaluated using ANOVA, principal component analysis (PCA), and hierarchical cluster analysis (HCA). Human health risks were assessed via Hazard Index (HI) and Lifetime Cancer Risk (LTCR) models based on the inorganic arsenic fraction. Storm-cast macroalgae exhibited a senescent post-detachment profile characterized by significant potassium and iodine leaching (p < 0.05) and iron enrichment from sediment entrapment. Despite leaching, iodine levels (up to 3.8 mg/g d.w.) satisfied pharmacopoeial minimums, though autumn White Sea samples exceeded the upper limit, necessitating blending with lower-iodine material. Toxic heavy metals remained below quantification limits, and total arsenic was well within regulatory thresholds. PCA confirmed that biomass physiological state is the primary driver of elemental variance. Adult consumption of storm-cast macroalgae was safe, whereas the pediatric HI exceeded 1.0. Overall, Arctic storm-cast macroalgae exhibit a high level of elemental purity, representing a promising raw material with a low chemical health risk for potential functional food and pharmaceutical applications. Full article
(This article belongs to the Special Issue Harnessing Microalgae and Seaweed for the Food Sector, 2nd Edition)
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15 pages, 611 KB  
Article
Prognostic Value of the Systemic Immune-Inflammation Index in Advanced Endometrial Cancer Treated with Pembrolizumab–Lenvatinib: A Retrospective Real-World Study
by Eleonora Palluzzi, Amedeo Cefaliello, Olga Martelli, Mariagrazia Distefano, Carolina Maria Sassu, Valentina Weger, Serena Maria Boccia, Laura Vertechy, Giorgia Russo, Luca Romano, Giacomo Corrado, Carolina Bottoni, Diana Giannarelli, Christian Marth, Anna Fagotti, Francesco Fanfani and Claudia Marchetti
Curr. Oncol. 2026, 33(8), 441; https://doi.org/10.3390/curroncol33080441 - 23 Jul 2026
Viewed by 60
Abstract
Background: The prognostic role of the Systemic Immune-Inflammation Index (SII) in patients with endometrial cancer (EC) treated with pembrolizumab plus lenvatinib (Len-Pem) is unknown. In this study, the association between baseline SII and progression-free survival (PFS) was evaluated. Methods: This is a monocentric, [...] Read more.
Background: The prognostic role of the Systemic Immune-Inflammation Index (SII) in patients with endometrial cancer (EC) treated with pembrolizumab plus lenvatinib (Len-Pem) is unknown. In this study, the association between baseline SII and progression-free survival (PFS) was evaluated. Methods: This is a monocentric, observational, retrospective/ambispective study including patients with advanced, recurrent, or metastatic mismatch repair proficient (pMMR) EC treated with Len-Pem. Results: Fifty-three patients were enrolled, with a median age of 64 years. Median PFS in the overall population was 7.1 months; median OS was 15 months. Patients with baseline SII ≤ 540 had significantly longer PFS (12.5 months) compared to those with SII > 540 (5.5 months; HR 2.94, p = 0.004). Higher SII was also significantly associated with increased risk of specific toxicities, including nausea, anorexia, and vomiting. The Overall Response Rate (ORR) was 42%, and Disease Control Rate (DCR) was 71%. Conclusion: Our real-world study supports the hypothesis-generation of a prognostic role for SII in predicting outcomes and toxicity in EC patients treated with Len-Pem. SII may serve as a cost-effective, accessible biomarker to stratify patients and hypothetically guide clinical decision-making. Further prospective studies are warranted to validate its clinical utility and to optimize dosing strategies that balance efficacy and tolerability. Full article
(This article belongs to the Section Gynecologic Oncology)
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17 pages, 8445 KB  
Article
Lycium barbarum Polysaccharide Stabilized Selenium Nanoparticles Exhibit Antibacterial Activity and Ameliorate Escherichia coli-Induced Diarrhea in Mice
by Kehan Liu, Wanhe Luo, Md. F. Kulyar, Boyi Zhao, Runjuan Yang, Jiabin Zhang, Ling Zhao, Jianzhong He, Mohammad Mehedi Hasan, Jindong Gao and Mengdi Zhang
Nanomaterials 2026, 16(15), 901; https://doi.org/10.3390/nano16150901 - 23 Jul 2026
Viewed by 148
Abstract
Lycium barbarum polysaccharides are major bioactive constituents of Lycium barbarum fruit and are widely recognized for antioxidant, immunomodulatory, and intestinal protective activities. Selenium nanoparticles are considered a safer selenium formulation than conventional inorganic selenium because they generally provide improved bioavailability and reduced toxicity. [...] Read more.
Lycium barbarum polysaccharides are major bioactive constituents of Lycium barbarum fruit and are widely recognized for antioxidant, immunomodulatory, and intestinal protective activities. Selenium nanoparticles are considered a safer selenium formulation than conventional inorganic selenium because they generally provide improved bioavailability and reduced toxicity. In this study, Lycium barbarum polysaccharide-stabilized selenium nanoparticles were prepared under mild conditions, characterized, and evaluated for antibacterial, antibiofilm, and antidiarrhoeal activities. The optimized nanoparticles exhibited a hydrodynamic diameter of 304.4 ± 32.9 nm, a polydispersity index of 0.369 ± 0.05, and a zeta potential of −20.8 ± 1.5 mV, indicating good colloidal stability. Scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy supported the structural assignment of spherical elemental selenium particles with a polysaccharide-rich surface layer. In vitro assays showed concentration-dependent inhibition of Escherichia coli, with minimum inhibitory and minimum bactericidal concentrations of 100 and 200 μg Se/mL, respectively. Biofilm formation was also markedly reduced, and scanning electron microscopy demonstrated severe bacterial surface damage after treatment. In a KM mouse model of Escherichia coli-induced diarrhea, oral administration of the nanoparticles significantly lowered diarrhea scores, improved body weight recovery, and alleviated intestinal mucosal injury compared with untreated infected mice. Major organs showed no obvious histopathological abnormalities under the experimental conditions. Overall, these findings identify Lycium barbarum polysaccharide-stabilized selenium nanoparticles as a promising selenium-based nanomaterial for controlling bacterial diarrhea and protecting intestinal health. These results provide a practical foundation for future mechanistic, pharmacokinetic, microbiological, and translational studies aimed at broader intestinal applications. Full article
(This article belongs to the Special Issue Antimicrobial Nanomaterials: Development and Applications)
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38 pages, 1503 KB  
Review
Nanoparticle-Mediated Radiosensitization in Breast Cancer: A Systematic Review of Preclinical Evidence and Translational Challenges
by Sorinel Lunca, Stefan Morarasu and Gabriel Mihail Dimofte
Int. J. Mol. Sci. 2026, 27(14), 6522; https://doi.org/10.3390/ijms27146522 - 22 Jul 2026
Viewed by 109
Abstract
Radiotherapy is a cornerstone of breast cancer treatment, but its efficacy is frequently limited by intrinsic and acquired radioresistance as well as dose-limiting toxicity to surrounding normal tissues. Nanoparticle-mediated radiosensitization has emerged as a promising strategy to enhance the therapeutic index of irradiation [...] Read more.
Radiotherapy is a cornerstone of breast cancer treatment, but its efficacy is frequently limited by intrinsic and acquired radioresistance as well as dose-limiting toxicity to surrounding normal tissues. Nanoparticle-mediated radiosensitization has emerged as a promising strategy to enhance the therapeutic index of irradiation by combining physical dose amplification with biological, microenvironmental, and immunological modulation. In this systematic review, we evaluated preclinical evidence on nanoparticle-mediated radiosensitization in breast cancer, with emphasis on nanoplatform design, mechanistic patterns, therapeutic efficacy, and translational relevance. A total of 66 studies published between 2015 and 2026 were included. The identified systems encompassed a broad range of materials, including gold-, silver-, platinum-, bismuth-, gadolinium-, polymer-, lipid-, and hybrid-based nanoplatforms, frequently incorporating targeting ligands, catalytic components, biomimetic coatings, or therapeutic payloads. Enhanced radiation responses were most commonly associated with high-atomic-number (high-Z)-mediated energy deposition, increased reactive oxygen species generation, and enhanced DNA damage persistence. Additional mechanisms, including redox modulation, hypoxia targeting, regulated cell death, and immune activation, reflect the evolution of nanoparticle-assisted radiotherapy from predominantly physical radioenhancement toward multifunctional physicobiological strategies. Triple-negative breast cancer models predominated throughout the literature. Across preclinical models, nanoparticle-assisted irradiation consistently improved clonogenic survival, tumor control, and, in selected studies, survival. However, substantial heterogeneity in study design and limited use of rigorous radiobiological endpoints restricted cross-study comparability. The available preclinical evidence indicates that the most promising nanoparticle-mediated radiosensitization strategies integrate physical dose enhancement with biologically active mechanisms targeting oxidative stress, hypoxia, persistent DNA damage, immune signaling, and tumor microenvironmental resistance. Collectively, these findings suggest that the field is evolving from predominantly physical radioenhancement toward multifunctional, mechanism-driven physicobiological strategies. However, clinical translation remains constrained by methodological heterogeneity and limited radiobiological validation, highlighting the need for standardized preclinical evaluation and clinically feasible nanoplatforms tailored to subtype-specific mechanisms of radioresistance. Full article
(This article belongs to the Section Molecular Oncology)
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14 pages, 886 KB  
Article
The Effect of Hesperidin on Inflammatory Response and Oxidant–Antioxidant Systems in Benzo[a]pyrene-Exposed Non-Small Cell Lung Cancer (A549) Cells
by Ahmet Büyükben
Molecules 2026, 31(14), 2548; https://doi.org/10.3390/molecules31142548 - 22 Jul 2026
Viewed by 186
Abstract
Lung cancer represents a substantial global oncology burden, exhibiting mortality rates that surpass those of prostate, pancreatic, and breast cancers. Extensive research has established a correlation between exposure to polycyclic aromatic hydrocarbon mixtures—particularly those containing benzo(a)pyrene (BaP)—and elevated risks of pulmonary and dermal [...] Read more.
Lung cancer represents a substantial global oncology burden, exhibiting mortality rates that surpass those of prostate, pancreatic, and breast cancers. Extensive research has established a correlation between exposure to polycyclic aromatic hydrocarbon mixtures—particularly those containing benzo(a)pyrene (BaP)—and elevated risks of pulmonary and dermal malignancies across various species, including humans. Hesperidin (HSP), a prominent bioactive flavonoid found in citrus fruits and medicinal herbs such as Hypericum perforatum, is recognized for its diverse pharmacological properties. The present study aimed to elucidate the antioxidant and anti-inflammatory efficacy of HSP against BaP-induced toxicity in the A549 non-small cell lung cancer (NSCLC) cell line. Following the determination of application concentrations via MTT assay, the modulatory effects of HSP on cellular proliferation, oxidative stress markers (TAS, TOS, and OSI), and key pro-inflammatory cytokines (TNF−α, IL−1β, and TGF−β) were systematically evaluated. Isolated exposure to BaP predominantly triggered a targeted upregulation of IL-1β; however, hesperidin demonstrated unexpected pro-oxidant dynamics, characterized by a substantial drop in TAS alongside a concurrent elevation in both TOS and OSI profiles, especially at maximum-dose concentrations. Notably, combining BaP with this heightened hesperidin regimen manifested the most severe oxidative distress phenotype, implying a synergistic pro-oxidant cascade between the two agents. On the contrary, minimized concentrations of hesperidin exerted explicit cytoprotective mitigation against the BaP-induced surge in IL-1β, thereby confirming a highly delicate and narrow therapeutic index for this flavonoid. Full article
(This article belongs to the Special Issue Environmental Pollutants and Oxidative Stress Chemistry)
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20 pages, 880 KB  
Article
Characteristics and Carcinogenic Risk of PM2.5-Bound Polycyclic Aromatic Hydrocarbons from Charcoal Barbecue (Moo Kratha) Restaurants in Chiang Mai, Thailand
by Thanawat Komonnithiphong, Kotchakorn Khammoon, Sakaewan Ounjaijean, Kongsak Boonyapranai, Hataichanok Chuljerm, Kanokwan Kulprachakarn, Wiritphon Khiaolaongam, Anurak Wongta, Surat Hongsibsong and Sawaeng Kawichai
Toxics 2026, 14(7), 643; https://doi.org/10.3390/toxics14070643 - 22 Jul 2026
Viewed by 160
Abstract
Barbecue (Moo Kratha) restaurants are prevalent in Chiang Mai City, Thailand. However, their PM2.5-bound polycyclic aromatic hydrocarbon (PAH) emissions, compounded by the region’s severe seasonal smoke haze, remain poorly characterized. This study investigated the chemical composition and carcinogenic risk of PM [...] Read more.
Barbecue (Moo Kratha) restaurants are prevalent in Chiang Mai City, Thailand. However, their PM2.5-bound polycyclic aromatic hydrocarbon (PAH) emissions, compounded by the region’s severe seasonal smoke haze, remain poorly characterized. This study investigated the chemical composition and carcinogenic risk of PM2.5-bound PAHs in this present environment. Ten PM2.5 samples were collected from ten charcoal Moo Kratha restaurants during peak evening hours in February 2026 (early dry season) using a portable air sampler operated as a fixed-location (area) sampler positioned at the customer dining table (2 L min−1, 180 min) on quartz fiber filters, and the 16 US EPA priority PAHs were analyzed by GC-MS. Carcinogenic risk was assessed using benzo[a]pyrene toxicity equivalent (TEQBaP) concentrations and incremental lifetime cancer risk (ILCR) for adult and child customers (diners) via the inhalation pathway. The mean concentrations of PM2.5 and total PAHs were 87.64 µg m−3 and 132.74 ng m−3, respectively, with carcinogenic PAHs contributing 52.3%; the mean TEQBaP of 15.34 ng m−3 provides an internal index of the carcinogenic potency of the PAH mixture. The mean inhalation ILCR for a frequent diner was 2.82 × 10−5 for adults and 2.12 × 10−5 for children, rising to 6.16 × 10−5 and 4.62 × 10−5, respectively, at the most contaminated site; even an occasional (monthly) diner exceeded the 10−6 negligible threshold. These findings indicate that charcoal Moo Kratha restaurants are distinct, persistent sources of carcinogenic PAHs that place diners within the upper part of the tolerable cancer-risk range; worker exposure is expected to be higher but was not quantified here, underlining the need for ventilation and occupational-health strategies. Full article
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23 pages, 2227 KB  
Article
Physicochemical Stability, Sensory Acceptance, and Biological Impact of Green Tea Kombucha Flavored with Native Cerrado Fruits (Spondias mombin L. and Anacardium occidentale L.)
by Maria Fernanda Rossetti Rogerio, Ana Elisa Barbosa Siqueira, Maria Isabela da Silva Figueiredo, Jasmim Esmeralda Silva Lima, Marcos Antônio Soares, Claudia Puerari, Maressa Caldeira Morzelle and Juliana Aparecida Correia Bento
Beverages 2026, 12(7), 82; https://doi.org/10.3390/beverages12070082 - 22 Jul 2026
Viewed by 169
Abstract
Kombucha is a functional beverage produced through the fermentation of Camellia sinensis by a symbiotic culture of bacteria and yeast (SCOBY). Incorporating cashew (Anacardium occidentale L.) and Cajá (Spondias mombin L.) pulps represents a value-addition strategy to mitigate the post-harvest perishability [...] Read more.
Kombucha is a functional beverage produced through the fermentation of Camellia sinensis by a symbiotic culture of bacteria and yeast (SCOBY). Incorporating cashew (Anacardium occidentale L.) and Cajá (Spondias mombin L.) pulps represents a value-addition strategy to mitigate the post-harvest perishability of native Cerrado fruits. This study evaluated physicochemical kinetics, 21-day refrigerated shelf life, consumer acceptance, and biological effects in Caenorhabditis elegans of flavored kombuchas. During a 9-day primary fermentation, the pH decreased to 2.95 while total acidity reached 5.38%. Following flavoring (10% v/v pulp/juice), cashew kombucha exhibited the highest total phenolic content (4.19 mg GAE/mL) and ferric reducing power (FRAP), whereas Cajá kombucha showed superior DPPH scavenging activity (1236 µM TroloxE/mL). Refrigerated storage (4 °C) maintained high counts of viable microorganisms (>105 CFU/mL), though active residual fermentation induced ongoing sugar cleavage and a transient yeast proliferation peak on day 7 (8.15 log CFU/mL in Cajá kombucha). Toxicity assays using C. elegans revealed the initial mortality (31.5–62.5%); however, adjusting the pH to near-neutrality restored high organism viability (<10% mortality), confirming that mortality was acidity-driven. In pH-adjusted media, cashew kombucha promoted a modest extension of nematode lifespan, whereas Cajá kombucha reduced lipid accumulation. Sensory testing revealed moderate consumer acceptance, with cashew kombucha achieving a higher Acceptance Index (72.92%) than Cajá (67.26%). Overall, fruit supplementation enriches the bioactive potential of green tea kombucha, provided that post-fermentation acidity is appropriately managed. Full article
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23 pages, 14321 KB  
Article
Characterization of Forestiera tomentosa Fruit: Proximate Composition, Physicochemical Parameters, Phenolic Content, Antioxidant Capacity, and Toxicological Assessment
by Salvador Hernández-Estrada, Luis Antonio Ramirez-Contreras, Luis Alfonso Hernández-Villaseñor, Jorge Manuel Silva-Jara, Efigenia Montalvo-González, Zuamí Villagrán, Noé Rodríguez-Barajas, Jorge L. Mejía-Méndez, Carlos Arnulfo Velázquez-Carriles, Martin Zermeño-Ruiz and Luis Miguel Anaya-Esparza
Molecules 2026, 31(14), 2542; https://doi.org/10.3390/molecules31142542 - 22 Jul 2026
Viewed by 454
Abstract
The demand for sustainable nutrients and bioactive compounds has increased interest in underutilized wild plants. Forestiera tomentosa, a Mexican drupe-bearing species, is largely unexplored. This study evaluated the proximate composition, physicochemical and functional properties, phenolic profile, antioxidant capacity, and toxicological safety of [...] Read more.
The demand for sustainable nutrients and bioactive compounds has increased interest in underutilized wild plants. Forestiera tomentosa, a Mexican drupe-bearing species, is largely unexplored. This study evaluated the proximate composition, physicochemical and functional properties, phenolic profile, antioxidant capacity, and toxicological safety of F. tomentosa fruit. The fruit showed high carbohydrate content [71.94% dry weight (DW)], with notable crude fiber (7.90% DW), protein (7.39% DW), and lipid (4.30% DW) contents. Analysis revealed a mildly acidic pH (5.66), titratable acidity of 0.32%, and total soluble solids of 2.33 °Brix. The fruit powder had a low water activity (0.42) and a favorable water solubility index (56.10%), oil absorption (4.54%), and foaming capacity (19.71%). The fruit contained high levels of soluble phenols (280.42 mg GAE/g DW), flavonoids (98.89 mg CE/g DW), anthocyanins (54.53 mg C3G/g DW), and condensed tannins (94.05 mg CE/g DW). High-performance liquid chromatography identified 20 phenolic compounds, with 3-(4-hydroxyphenyl) propionic acid, syringic acid, catechin, epicatechin, and gallocatechin being predominant. The fruit showed significant radical scavenging and reducing potential (DPPH, ABTS, and FRAP). Toxicological evaluation using the Artemia salina bioassay showed a 100% survival rate across all concentrations, indicating no acute toxicity. In silico ADMET predictions revealed favorable pharmacokinetic properties, including high intestinal absorption and compliance with Lipinski’s rule of five. These findings position F. tomentosa as a promising, non-toxic source of functional ingredients for the food, nutraceutical, and pharmaceutical industries, supporting biodiversity conservation and sustainable resource utilization. Further studies are needed to evaluate the potential health benefits of this fruit in vitro and in vivo. Full article
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15 pages, 689 KB  
Article
Investigation of the Anti-Toxoplasma gondii Potential of Loratadine
by Stephanie Ortega Alves, Ingrid de Oliveira Dias, Gabriel Candido Moura, Samuel Cota Teixeira and Juliana Quero Reimão
Pathogens 2026, 15(7), 773; https://doi.org/10.3390/pathogens15070773 - 22 Jul 2026
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Abstract
Toxoplasmosis remains a major global health concern, particularly in immunocompromised individuals and pregnant women, while currently available therapies are associated with significant toxicity and limited efficacy against chronic infection. Drug repurposing represents an attractive strategy for the identification of safer and more effective [...] Read more.
Toxoplasmosis remains a major global health concern, particularly in immunocompromised individuals and pregnant women, while currently available therapies are associated with significant toxicity and limited efficacy against chronic infection. Drug repurposing represents an attractive strategy for the identification of safer and more effective anti-Toxoplasma gondii agents. This study investigated the antiparasitic potential of loratadine, a second-generation antihistamine, using an integrated in silico, in vitro, and in vivo approach. The anti-T. gondii activity of loratadine was evaluated through β-galactosidase-based proliferation assays, reversibility assays, and experiments using pretreated tachyzoites. In vivo efficacy was assessed in murine models of acute and chronic toxoplasmosis. Disease progression, survival, parasite burden, and cerebral cyst formation were analyzed following treatment. Loratadine inhibited the intracellular proliferation of T. gondii tachyzoites in a concentration-dependent manner and induced partially irreversible effects on parasite viability after drug withdrawal. Pretreatment of extracellular tachyzoites produced limited effects, suggesting that loratadine predominantly acts during the intracellular stage of infection. In the acute toxoplasmosis model, loratadine treatment delayed disease progression, prolonged animal survival, and significantly reduced the number of tachyzoites recovered from the peritoneal cavity. In the chronic infection model, treatment significantly decreased both the number and size of cerebral cysts, although these findings do not demonstrate cyst eradication or direct bradyzoite killing. Despite its measurable biological activity, loratadine exhibited a relatively low in vitro selectivity index, highlighting the need for further optimization. These exploratory findings identify loratadine as a promising lead compound (hit) for further optimization rather than an immediately translatable therapeutic candidate. Additional medicinal chemistry, pharmacokinetic, mechanistic, and confirmatory preclinical studies will be required to determine its potential for anti-T. gondii drug development. Full article
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26 pages, 6272 KB  
Article
Assessment of Intrinsic Hazards in an Energy-Integrated Gas Oil Hydrocracking Process
by Juan Quintero-Tabares, Segundo Rojas-Flores and Ángel Darío González-Delgado
Sustainability 2026, 18(14), 7441; https://doi.org/10.3390/su18147441 - 21 Jul 2026
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Abstract
This study assesses the intrinsic hazards of an energy-integrated gas oil hydrocracking process from a sustainability-oriented process safety perspective. Hydrocracking units are essential in modern refineries for upgrading heavy gas oil fractions into higher-value fuels; however, they operate under severe conditions involving high [...] Read more.
This study assesses the intrinsic hazards of an energy-integrated gas oil hydrocracking process from a sustainability-oriented process safety perspective. Hydrocracking units are essential in modern refineries for upgrading heavy gas oil fractions into higher-value fuels; however, they operate under severe conditions involving high temperatures, elevated pressures, hydrogen-rich environments, complex process structures, and large inventories of hazardous substances. In this context, improving energy efficiency through heat integration must be evaluated together with its implications for inherent safety and sustainable process design. The Inherent Safety Index (ISI) methodology was applied at the conceptual design stage to quantify the intrinsic risk level of the process and identify the main contributors to chemical and process-related hazards. The results yielded a total ISI value of 46, composed of a chemical safety index of 26 and a process safety index of 20, indicating a high intrinsic hazard level. The most significant contributors were toxic exposure (ITOX = 6), inventory magnitude (II = 5), and process structure (IST = 5), while the large ISBL inventory of 2838.3 t, together with operating conditions reaching 456.4 °C and 166.8 bar, substantially increased the inherent risk of the system. Although energy integration contributes to improved thermal performance, the results indicate that it does not significantly reduce the intrinsic hazard level. Sensitivity analysis showed that optimization of operating temperature and pressure could reduce the ISI from 46 to approximately 43. These findings demonstrate that the intrinsic risk of energy-integrated hydrocracking systems is primarily governed by operating severity, hazardous material inventories, and toxicity, highlighting the importance of incorporating inherent safety principles during the conceptual design stage to achieve safer, more resilient, and more sustainable refinery operations. Full article
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14 pages, 56318 KB  
Article
Trypanocidal Activity of Crude Extracts from Montagnula sp., an Endophytic Fungus Isolated from Lippia alba
by Karen Alexandra Caicedo-Jiménez, Liliana Torcoroma García, Erika Marcela Moreno, Catalina Salgado-Salazar, Julie Fernanda Benavides Arévalo and Beatriz Elena Guerra-Sierra
J. Fungi 2026, 12(7), 536; https://doi.org/10.3390/jof12070536 - 20 Jul 2026
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Abstract
Chagas disease, caused by Trypanosoma cruzi, remains a neglected tropical infection with limited therapeutic options and significant drug-related toxicity. Endophytic fungi are emerging as sustainable sources of bioactive metabolites with potential antiparasitic activity. In this study, endophytic fungi isolated from the medicinal [...] Read more.
Chagas disease, caused by Trypanosoma cruzi, remains a neglected tropical infection with limited therapeutic options and significant drug-related toxicity. Endophytic fungi are emerging as sustainable sources of bioactive metabolites with potential antiparasitic activity. In this study, endophytic fungi isolated from the medicinal plant Lippia alba were screened for trypanocidal activity. Crude extracts from seven isolates were tested against epimastigote and amastigote forms of T. cruzi, together with cytotoxicity assays in J774A.1 murine macrophages. The crude extract of Montagnula sp. exhibited the strongest trypanocidal activity (IC50 = 22.1 ± 0.5 μg/mL for epimastigotes and 29.2 ± 3.0 μg/mL for amastigotes), comparable to benznidazole, with low toxicity (CC50 > 600 μg/mL) and a high selectivity index (>26). Morphological and mitochondrial analyses demonstrated preservation of host-cell integrity and mitochondrial function, in contrast to the reference drug. UHPLC-ESI-HRMS profiling identified phenolic and terpenoid compounds, including caffeic acid, ferulic acid, naringenin, apigenin, and ursolic acid, which may underlie the observed biological activity. To our knowledge, this study provides the first evidence of trypanocidal activity in an endophytic Montagnula species and highlights endophytic fungi as promising platforms for the discovery of novel anti-T. cruzi agents. Full article
(This article belongs to the Special Issue Bioactive Secondary Metabolites from Fungi)
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