Public health concerns about organic UV filters are increasing, yet exposure levels among children remain poorly characterized. In particular, the contribution of non-sunscreen sources is still unclear. To address this gap, we recruited 301 children aged 6-11 years with limited sunscreen use from Indonesia, Thailand, and Saudi Arabia during 2017-2018. Human biomonitoring of octocrylene (OC), 2-ethylhexyl salicylate (EHS), and homosalate (HMS) was conducted by analyzing eight novel urinary biomarkers using online-SPE-LC-MS/MS. Daily intakes were estimated by reverse dosimetry. Our results demonstrated widespread exposure to OC and EHS in children, whereas HMS exposure was rare. Significant inter-country differences were observed, with the highest concentrations of CPAA (biomarker for OC) in Thai children (92.3% > LOQ) and of 5cx-EPS (for EHS) in Indonesian children (76.4% >LOQ). Reported sunscreen use was not associated with urinary metabolite concentrations. None of the metabolites exceeded the HBM-I value; however, the maximum 5cx-EPS concentration (6.26 µg/L) approached this threshold. Among the children, OC and EHS exposures were not associated with reported sunscreen use, but were significantly associated with other potential sources, including antimicrobial soap use and fish consumption. Several country-specific sources were also identified: OC exposure was associated with recent wardrobe replacement (Indonesia), and frequent use of toilet detergents (Thailand), while EHS exposure was associated with the use of bath products in Indonesia and paper-based food storage containers (Saudi Arabia). These findings establish baseline exposure levels of major organic UV filters in children and highlight the importance of non-sunscreen sources in shaping exposure pathways.

Recurrent pregnancy loss (RPL) remains a complex reproductive challenge, often linked to oxidative stress (OS) and DNA damage. Emerging evidence indicates that rare earth elements, including ruthenium (Ru), may disrupt cellular redox balance and impair genomic stability, thereby posing a potential reproductive risk. This study aimed to investigate whether elevated serum Ru levels are associated with OS and DNA damage in individuals experiencing RPL. A case–control study was conducted involving women with a history of RPL (n = 30) and healthy pregnant controls (n = 30). OS was assessed by quantifying malondialdehyde (MDA) and glutathione (GSH), while DNA damage was evaluated using 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels. Serum Ru was quantified by Inductively Coupled Plasma Mass Spectrometer. The association between Ru and oxidative/DNA damage markers in both groups was evaluated by Pearson correlation analysis. Serum MDA levels were higher in the RPL group (6.08 ± 0.52 nmol/ml) relative to controls (3.36 ± 0.43 nmol/ml, P < 0.001), while GSH levels were reduced (7.43 ± 0.97 mg/ml as opposed to 8.84 ± 0.61 mg/ml, P < 0.001). Similarly, 8-OHdG concentrations were elevated in RPL (23.90 ± 8.64 ng/ml) versus controls (10.12 ± 3.53 ng/ml, P < 0.001). Serum Ru levels were also significantly increased in RPL women (0.002 ± 0.0001 ppb) as against controls (0.001 ± 0.0001 ppb, P < 0.001). Correlation analysis revealed that in the RPL group, Ru was positively associated with MDA (r = 0.47, P < 0.01) and 8-OHdG (r = 0.47, P < 0.01) and negatively with GSH (r = − 0.8, P < 0.001). In contrast, no significant correlations were observed in controls (MDA: r = 0.17, P = 0.35; GSH: r = 0.05, P = 0.75; 8-OHdG: r = 0.32, P = 0.07). Scatter plots further demonstrated positive trends of Ru with MDA and 8-OHdG, and an inverse association with GSH in RPL women. After adjusting for age, BMI, and parity, serum Ru remained a significant independent predictor of OS and DNA damage in women with RPL. Ru was positively associated with MDA (β = +0.18, 95% CI: 0.10–0.26, P < 0.001) and 8-OHdG (β = +0.72, 95% CI: 0.41–1.03, P < 0.001), and inversely with GSH (β = − 0.60, 95% CI: − 0.62 − 0.90, P < 0.001), explaining 38–63% of the variance. This study demonstrates that women with RPL exhibit elevated serum ruthenium levels, which are strongly associated with enhanced OS, reduced antioxidant defense, and increased DNA damage. The positive correlations of Ru with MDA and 8-OHdG, alongside its inverse association with GSH, underscore its potential role as a contributing factor in RPL pathophysiology. These findings highlight Ru as an independent predictor of oxidative imbalance and genomic instability in RPL, suggesting that monitoring environmental or therapeutic Ru exposure may be critical for reproductive health. Further large-scale studies are warranted to confirm these associations and clarify underlying mechanisms.

Glutathione peroxidase 1 (GPx1) activity, gene expression, and several oxidative stress (OS) marker levels were investigated in the senescent passage (P) 20, 25, and 30 fibroblasts cultured in media supplemented with increasing Se-Methylselenocysteine (MSC) increments. While GPx1 activity slightly increased in cells grown in standard culture medium (CM1) compared to primary P5 cells, the enzyme exhibited significant MSC-dose-dependent elevations in cells cultured in MSC-supplemented media (CM3-CM6) compared to CM1 (p<0.001). GPx1 activity in CM5-incubated P30, P25, and P20 cells equaled 5.99±0.62, 4.72±0.48, and 4.06±0.36 µmoles/min/mg protein respectively (p<0.001), with percentage increases of 250% in P30 cells compared to 190% in P20 cells when cultured with CM1. Similarly, GPx1 expression was markedly upregulated in CM2, CM4, and CM6-incubated cells compared to primary P5 cells (p<0.001), with fold change values of 1.51±0.12, 1.99±0.16, and 2.31±0.19 in P20 cells. Percentage upregulations were 50.0±3.68%, 89.5±7.11%, and 126.5±9.74% in CM2, CM4, and CM6-incubated P20 cells respectively, and reached 248.0±18.6% in P30 cells at the highest MSC concentration. Concurrently, OS marker levels were substantially higher in CM1-cultured P25 and P30 senescent cells compared to primary P5 cells (p<0.001). Furthermore, hydrogen peroxide levels were significantly reduced in CM3-incubated cells compared to CM1 (p<0.01), reaching the lowest values in CM6 (p<0.001), with reductions of approximately 11.5%, 40%, 57%, and 58% in P30 CM3, CM4, CM5, and CM6-incubated cells respectively. MSC-Km values for GPx1 were 0.87, 1.13, and 1.92 µM in P20, P25, and P30 cells, respectively, with corresponding Vmax values of 4.59, 5.68, and 7.94 µmole/min/mg protein. These findings suggest that senescent cells utilize higher amounts of MSC to upregulate GPx1 expression and maximize its activity, supporting using Se supplements to combat OS.

We aimed to explore the role of Indium (In), Terbium (Tb), Yttrium (Y), and Lanthanum (La) in the serum of women with recurrent pregnancy loss (RPL) and compare them to controls. Additionally, the study aimed to examine the relationship between REE levels and oxidative DNA damage, to identify potential risk factors contributing to RPL. This case–control study included 30 RPL cases and 30 controls with uncomplicated pregnancy. Inductively Coupled Plasma Mass Spectrometer was used to evaluate levels of In, Tb, Y, and La in the serum samples in both groups. The relationship between REE levels, Total Antioxidant Capacity (TAC), and DNA damage was studied by correlation analysis. There was a significant increase in levels of In, Tb, Y, and La in the serum of the RPL group in contrast to the control group (P < 0.001). Furthermore, a negative correlation was observed between increased Y, Tb, La, and TAC in RPL cases (significant at P < 0.05), indicative of weakened antioxidant defenses. Moreover, increased levels of Y, Tb, and La exhibited a positive correlation with the DNA damage marker, statistically significant at P < 0.05. These findings highlight the potential role of oxidative stress-induced DNA damage and metal intoxication in the development of RPL, underscoring the importance of further research to clarify underlying mechanisms and develop preventive strategies.

Objective: To evaluate the levels of serum rare earth elements (REEs): lutetium [Lu], praseodymium [Pr], samarium [Sm], dysprosium [Dy], and cerium [Ce] in pregnant women with recurrent pregnancy loss (RPL) and evaluate their relationship with total antioxidant capacity (TAC) and 8-hydroxy-2 '-deoxyguanosine (8-OHdG), a marker of DNA damage. Methods: A case-controlled study was conducted on a cohort of 60 female participants, with first-trimester healthy pregnant women as the control group and pregnant women with a history of consecutive abortions as the recurrent pregnancy loss (RPL) group. Following blood collection, serum concentrations of Lu, Pr, Sm, Dy, and Ce were measured using an inductively coupled plasma mass spectrophotometer (ICP-MS). Oxidative stress and DNA damage were evaluated through TAC and DNA damage marker (8-OHdG). Results: Serum levels of Lu, Pr, Sm, Dy, and Ce were higher in women with RPL compared with control (P < 0.001). Intriguingly, a strong significant negative correlation was observed between TAC and REEs (P < 0.05). Lu, Dy, and Ce demonstrated a significant positive correlation with increased DNA damage in the RPL group (P < 0.05). Contrary, there was no evidence of a correlation between 8-OHdG and Pr and Sm. Conclusion: The study highlights a potential association between Lu, Sm, Dy, and Ce and an increased risk of RPL, highlighting REE-induced toxicity as a major risk factor for RPL. The outcome of the study is to advance our understanding of the interplay between rare earth elements and RPL, with potential implications for reproductive medicine, environmental health, and the development of preventive strategies for individuals at risk of RPL.

Isothiazolinone preservatives (methylisothiazolinone (MIT) and methylchloroisothiazolinone (CMIT) are commonly used in cosmetics, industrial and household products. However, these isothiazolinone derivatives are known to cause allergic contact dermatitis. Hence, a sensitive, accurate, and reliable method for the detection of these compounds is thus warranted. The study aims to analyze concentrations of MIT and CMIT by high performance liquid chromatography. The analytical method used for quantification of MIT and CMIT in cosmetic products (leave-on-baby wet wipes) complies with the validation acceptance criteria (international standards ISO 5725, EU25 European Union for cosmetic regulations). MIT and CMIT were extracted and analyzed in leave-on baby wet-wipes collected from different stores in Riyadh city. Extraction was performed by ultrasonication of the samples, solid-phase extraction, and liquid-liquid extraction. Ten (10) µL of the sample was injected into the HPLC system and samples were analyzed with a mixture of acetic acid and methanol (80:20 v/v) in an isocratic mode. The flow rate was maintained at 1 mL/min. UV detection was performed at 274 nm. The results demonstrated recoveries between 90 and 106%, measurement uncertainty of C +/− 0.4% for methylisothiazolinone and C +/− 0.03% for methylchloroisothiazolinone, repeatability limit (r = 0.2%) and intermediate precision limit; R = 2% and R2 of 0.9996.

The tragic COVID-19 pandemic, which has seen a total of 655 million cases worldwide and a death toll of over 6.6 million seems finally tailing off. Even so, new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to arise, the severity of which cannot be predicted in advance. This is concerning for the maintenance and stability of public health, since immune evasion and increased transmissibility may arise. Therefore, it is crucial to continue monitoring antibody responses to SARS-CoV-2 in the general population. As a complement to polymerase chain reaction tests, multiplex immunoassays are elegant tools that use individual protein or peptide antigens simultaneously to provide a high level of sensitivity and specificity. To further improve these aspects of SARS-CoV-2 antibody detection, as well as accuracy, we have developed an advanced serological peptide-based multiplex assay using antigen-fused peptide epitopes derived from both the spike and the nucleocapsid proteins. The significance of the epitopes selected for antibody detection has been verified by in silico molecular docking simulations between the peptide epitopes and reported SARS-CoV-2 antibodies. Peptides can be more easily and quickly modified and synthesized than full length proteins and can, therefore, be used in a more cost-effective manner. Three different fusion-epitope peptides (FEPs) were synthesized and tested by enzyme-linked immunosorbent assay (ELISA). A total of 145 blood serum samples were used, compromising 110 COVID-19 serum samples from COVID-19 patients and 35 negative control serum samples taken from COVID-19-free individuals before the outbreak. Interestingly, our data demonstrate that the sensitivity, specificity, and accuracy of the results for the FEP antigens are higher than for single peptide epitopes or mixtures of single peptide epitopes. Our FEP concept can be applied to different multiplex immunoassays testing not only for SARS-CoV-2 but also for various other pathogens. A significantly improved peptide-based serological assay may support the development of commercial point-of-care tests, such as lateral-flow-assays.

To study the impact of heavy metals especially tellurium, thallium, and osmium, in recurrent pregnancy loss (RPL) and to study their association with antioxidant status and DNA damage.

Introduction The most challenging step in clinical research studies is patient recruitment. Many research studies do not reach their targets because of participant rejection. The purpose of this study was to assess patient as well as the community knowledge, motivation, and barriers to participate in genetic research. Methods A cross-section study was conducted between September 2018 and February 2020 using face-to-face interviews with candidate patients from outpatient clinics at King Fahad Medical City (KFMC), Riyadh, Saudi Arabia. Additionally, an online survey was conducted to assess the community’s knowledge, motivation and barriers to participate in genetic research studies. Results In total, 470 patients were interviewed for this study, with 341 being successfully recruited for the face to face interview, and the other patients being refused owing to time constraints. The majority percentage of the respondents were females. The respondents’ mean age was 30, and 52.6% reported having a college degree. The survey results from 388 participants illustrated that around 90% of the participants, participated voluntarily due to a good understanding of genetics studies. The majority held positive attitudes toward being part of genetic research, which exceeded the reported motivation score of >75%. The survey indicated that >90% of individuals were willing to participate to acquire therapeutic benefits or to receive continued aftercare. However, 54.6% of survey participants were worried about the side effects and the risks involved in genetic testing. A higher proportion (71.4%) of respondents reported that lack of knowledge about genetic research was one of the barriers to rejecting participation. Conclusion Respondents reported relatively high motivation and knowledge for participation in genetic research. However, study participants reported “do not know enough about genetic research” and “lack of time during clinic visit” as a barrier for participation in genetic research.

Background: Dystrophic Epidermolysis bullosa (DEB) is a rare, severe subtype of epidermolysis bullosa (EB), characterized by blisters and miliary rashes of the skin. Dystrophic EB (DEB) includes variants inherited both in an autosomal-dominant or autosomal-recessive manner. Recessive dystrophic EB (RDEB) is divided into many subtypes and prevails as a result of biallelic genetic mutations in COL7A1 gene encoding type VII collagen, a major stabilizing molecule of the dermo-epidermal junction. The blister formation is mainly due to the variable structural and functional impairment of anchoring fibrils in VII collagen (COLVII), responsible for the adhesion of the epidermis to the dermis. Method: Three Pakistani families (A, B and C) affected with congenital dystrophic epidermolysis bullosa were recruited in the present study. The whole-exome sequencing (WES) approach was utilized for the detection of the pathogenic sequence variants in probands. The segregation of these variants in other participants was confirmed by Sanger sequencing. Results: This study identified a novel missense variant c.7034G>A, p. Gly2345Asp in exon 91, a novel Frameshift mutation c.385del (p. His129MetfsTer18) in a homozygous form in exon no 3, and a previously known nonsense variation (c.1573 C>T; p. Arg525Ter) in exon 12 of COL7A1 gene in families A, B, and C, respectively, as causative mutations responsible for dystrophic epidermolysis bullosa in these families. Conclusion: Our study validates the involvement of the COL7A1 gene in the etiology of dystrophic epidermolysis bullosa. It further expands the COL7A1 gene mutation database and provides an additional scientific basis for diagnosis, genetic counseling, and prognosis purposes for EB patients.

The current study investigates the NLRP3's cytotoxicity inhibitory effect among ovarian cancer cells and how it interacts with Wnt/β-catenin in vitro conditions. Further, the study also analyzed the regulatory role of NLRP3 in resistance to gemcitabine among ovarian cancer cells and its underlying interaction mechanisms with Wnt/β-catenin in vitro. The current in vitro study detailed that when downregulating NLRP3, it could enhance the gemcitabine sensitivity in GRC cells. In case of gemcitabine-resistant cells, the up-regulation of NLRP3 can increase the drug-resistance through the activation of IL-1β, EMT and Wnt/β-catenin signaling pathways. High expression of miR-624-5p was recorded in ovarian drug resistant cancer cells and it also boosted the cell viabilities. NLRP3 can reinstate the functioning of miR-624-5p in drug resistant cells. This phenomenon concludes that NLRP3 is a promising therapeutic target and can be implemented in traditional chemotherapy to increase the efficacy of the treatment. The current study conducted in vitro experiments and the findings infer that the downregulation of NLRP3 can enhance the sensitivity of gemcitabine among GRC cells. This mechanism will increase the treatment efficacy by inhibiting the drug resistance in GRC. These two entities are the new promising biomarkers that can be used in the detection of platinum resistance in ovarian cancer patients and conduct novel clinical research.

Isolated congenital anosmia (ICA) is a rare entity worldwide with poorly understood genetic variation. The diagnosis of ICA is made by exclusion of acquired causes of anosmia. Additionally, magnetic resonance imaging in ICA is essential for diagnosis, as it shows reduced or absent development of olfactory bulbs and shallow olfactory sulci. Here, we present the case of a 21-year-old man who presented to our clinic with complete anosmia since birth. The patient's history was negative for acquired causes of anosmia, and the physical examinations of the ears, nose, throat, head, and neck were all not remarkable. Smell testing revealed complete anosmia. The CT imaging was unremarkable; however, magnetic resonance imaging of the anterior brain and olfactory region showed bilaterally absent olfactory bulbs and olfactory tracts, with a shallow olfactory groove. The patient was then subjected to whole exome sequencing. Bioinformatics analysis was performed on the 37 genes associated with olfactory dysfunction, in which a missense variant was identified in the HS6ST1(NM_004807.3) gene was identified, which insilico tools predicted to be likely pathogenic. The results of this patient's genetic analysis add to the possible genetic culprits reported in ICA cases. Additional genetic analyses are required to validate mutations and understand the heterogeneity of disease representation.

Nonylphenol (NP) is an endocrine disruptor and environmental contaminant. Yet, data on individual body burdens and potential health risks in humans, especially among children, are scarce. We analyzed two specific urinary NP metabolites, hydroxy-NP (OH-NP) and oxo-NP. In contrast to parent NP, OH-NP has a much higher urinary excretion fraction (Fue), and both are insusceptible to external contamination. We investigated spot urine samples from school children of Thailand (n = 104), Indonesia (n = 89), and Saudi Arabia (n = 108) and could quantify OH-NP in 100% of Indonesian and Saudi children (median concentrations: 8.12 and 8.57 μg/L) and in 76% of Thai children (1.07 μg/L). Median oxo-NP concentrations were 0.95, 1.10, and <0.25 μg/L, respectively, in line with its lower Fue. Median daily NP intakes (DIs), back-calculated from urinary OH-NP concentrations, were significantly higher in Indonesia and Saudi Arabia [0.47 and 0.36 μg/(kg bw·d), respectively] than in Thailand [0.06 μg/(kg bw·d)]. Maximum DIs were close to the preliminary tolerable DI of 5 μg/(kg bw·d) from the Danish Environmental Protection Agency. Dominant sources of exposure or relevant exposure pathways could not be readily identified by questionnaire analyses and also potentially varied by region. The novel biomarkers provide long-needed support to the quantitative exposure and risk assessment of NP.

Breast cancer (BCa) ranks first in incidence rate among cancers in Arab females. The association between genetic polymorphisms in tumor suppressor genes and the risk of BCa has been studied in many ethnic populations with conflicting conclusions while Arab females and Saudi Arabian studies are still lacking. We screened a cohort of Saudi BCa patients by NGS using a bespoke gene panel to clarify the genetic landscape of this population, correlating and assessing genetic findings with clinical outcomes. We identified a total of 263 mutations spanning 51 genes, including several frequently mutated. Among the genes analyzed, the highest mutation rates were found in PIK3CA (12.9%), BRCA2 (11.7%), BRCA1 (10.2%), TP53 (6.0%), MSH2 (3.8%), PMS2 (3.8%), BARD1 (3.8%), MLH1 (3.4%), CDH1 (3.0%), RAD50 (3.0%), MSH6 (3.0%), NF1 (2.6%), in addition to others. We identified multiple common recurrent variants and previously reported mutations. We also identified 46 novel variants in 22 genes that were predicted to have a pathogenic effect. Survival analysis according to the four most common mutations (BRCA1, BRCA2, TP53, and PIK3CA) showed reduced survival in BRCA1 and BRCA2-mutant patients compared to total patients. Moreover, BRCA2 was demonstrated as an independent predictor of reduced survival using independent Cox proportional hazard models. We reveal the landscape of the mutations associated with BCa in Saudi women, highlighting the importance of routine genetic sequencing in implementation of precision therapies in KSA.

Brain tumors are the leading cause of childhood cancer-related deaths. Similar to adult brain tumors, pediatric brain tumors are classified based on histopathological evaluations. However, pediatric brain tumors are often histologically inconsistent with adult brain tumors. Recent research findings from molecular genetic analyses have revealed molecular and genetic changes in pediatric tumors that are necessary for appropriate classification to avoid misdiagnosis, the development of treatment modalities, and the clinical management of tumors. As many of the molecular-based therapies developed from clinical trials on adults are not always effective against pediatric brain tumors, recent advances have improved our understanding of the molecular profiles of pediatric brain tumors and have led to novel epigenetic and immunotherapeutic treatment approaches currently being evaluated in clinical trials. In this review, we focus on primary malignant brain tumors in children and genetic, epigenetic, and molecular characteristics that differentiate them from brain tumors in adults. The comparison of pediatric and adult brain tumors highlights the need for treatments designed specifically for pediatric brain tumors. We also discuss the advancements in novel molecularly targeted drugs and how they are being integrated with standard therapy to improve the classification and outcomes of pediatric brain tumors in the future.

Phthalates are widely used in consumer products and are well-known for adverse endocrine outcomes. Di-(2-ethylhexyl) phthalate (DEHP), one of the most extensively used phthalates, has been rapidly substituted with alternative plasticizers in many consumer products. The aim of this study was to assess urinary phthalate and alternative plasticizer exposure and associated risks in children of three Asian countries with different geographical, climate, and cultural characteristics. Children were recruited from elementary schools of Saudi Arabia (n = 109), Thailand (n = 104), and Indonesia (n = 89) in 2017-2018, and their urine samples were collected. Metabolites of major phthalates and alternative plasticizers were measured in the urine samples by HPLC-MS/MS. Urinary metabolite levels differed substantially between the three countries. Metabolite levels of diisononyl phthalate (DiNP), diisodecyl phthalate (DiDP), di(2-ethylhexyl) terephthalate (DEHTP), and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) were the highest in Saudi children: Median urinary concentrations of oxo-MiNP, OH-MiDP, 5cx-MEPTP, and OH-MINCH were 8.3, 8.4, 128.0, and 2.9 ng/mL, respectively. Urinary DEHP metabolite concentrations were the highest in the Indonesian children. The hazard index (HI) derived for the plasticizers with antiandrogenicity based reference doses (RfDAA) was >1 in 86%, 80%, and 49% of the Saudi, Indonesian, and Thai children, respectively. DEHP was identified as a common major risk driver for the children of all three countries, followed by DnBP and DiBP depending on the country. Among alternative plasticizers, urinary DEHTP metabolites were detected at levels comparable to those of DEHP metabolites or higher among the Saudi children, and about 4% of the Saudi children exceeded the health based human biomonitoring (HBM)-I value. Priority plasticizers that were identified among the children of three countries warrant refined exposure assessment for source identification and relevant exposure reduction measures.

Despite the extensive use of cisplatin (CP) as a chemotherapeutic agent, its clinical use is often restricted by undesirable side effects, such as toxicity to normal tissues. The aim of this study was to probe the effect of a combinatorial treatment of low multiple doses of antioxidants on CP-induced toxicity and the mitochondrial apoptotic pathway in hepatocytes. Animals received a single toxic dose of CP (7.5 mg/kg body weight) with or without combined multiple doses of epigallocatechin gallate (EGCG) and coenzyme Q10 (CoQ10) (15 and 5 mg/kg body weight, respectively). CP-treated animals showed altered biochemical parameters, denoting hepatotoxicity, which was markedly improved by the multidose treatment with EGCG + CoQ10. The increased levels of oxidants found in the cytosolic and mitochondrial fractions isolated from the liver of CP-administered rats were significantly attenuated by the combinatorial doses of antioxidants. EGCG + CoQ10 ameliorated the CP-induced compromised antioxidant defenses, oxidative modification of macromolecules, decreased activities of respiratory chain enzymes, altered membrane depolarization, and swelling of liver mitochondria. Furthermore, EGCG + CoQ10 treatment inhibited CP-induced apoptosis by suppressing the activation and mitochondrial accumulation of proapoptotic proteins and preventing the inhibition of antiapoptotic protein expression, cytochrome c efflux, caspase-3 activation, and DNA fragmentation. Histological findings further confirmed the protective effects of EGCG + CoQ10 against CP-induced cellular injury. Our findings revealed that the combination of EGCG and CoQ10, owing to their individual antioxidant properties, can be an effective remedy, which by maintaining redox hemostasis attenuate the mitochondrial stress-mediated molecular and cellular processes involved in CP-induced liver toxicity and cell death.

Purpose: Redox homeostasis plays an important role in the osteogenic differentiation of human mesenchymal stem cells (hMSCs) for bone engineering. Oxidative stress (OS) is believed to induce osteoporosis by changing bone homeostasis. Selenium nanoparticles (SeNPs), an antioxidant with pleiotropic pharmacological activity, prevent bone loss. However, the molecular mechanism underlying the osteogenic activity during hMSCSeNP interaction is unclear. Methods: This study assessed the effects of different concentrations (25, 50, 100, and 300 ng/mL) of SeNPs on the cell viability and differentiation ability of human embryonic stem cell-derived hMSCs. In addition, we analyzed OS markers and their effect on mitogen-activated protein kinase (MAPK) and Forkhead box O-3 (FOXO3) during osteogenesis. Results: SeNPs increased the cell viability of hMSCs and induced their differentiation toward an osteogenic over an adipogenic lineage by enhancing osteogenic transcription and mineralization, while inhibiting Nile red staining and adipogenic gene expression. By preventing excessive reactive oxygen species accumulation, SeNPs increased antioxidant levels in hMSCs undergoing osteogenesis compared to untreated cells. In addition, SeNPs significantly upregulated the gene and protein expression of phosphorylated c-Jun N-terminal kinase (JNK) and FOXO3a, with no significant change in the expression levels of extracellular signal-related kinase (ERK) and p38 MAPK. Conclusion: The results approved that low concentrations of SeNPs might enhance the cell viability and osteogenic potential of hMSCs by moderating OS. Increased JNK and FOXO3a expression shows that SeNPs might enhance osteogenesis via activation of the JNK/FOXO3 pathway. In addition, SeNP co-supplementation might prevent bone loss by enhancing osteogenesis and, thus, can be an effective candidate for treating osteoporosis through cellbased therapy.