Trisomy 21 (Down syndrome) remains the most prevalent autosomal aneuploidy, necessitating accurate prenatal diagnosis. While cell-free fetal DNA (cffDNA)-based non-invasive prenatal testing (NIPT) has transformed screening, challenges persist in low fetal fraction cases and confined placental mosaicism. Integrating artificial intelligence (AI), multi-omics, and fetal cell-based approaches represents a paradigm shift toward comprehensive prenatal diagnostics. This AI-assisted meta-analysis evaluates NIPT platforms for Trisomy 21 detection, comparing cffDNA-based, SNP-based, digital PCR, and emerging fetal cell-based approaches. Following PRISMA guidelines, we systematically searched PubMed, Web of Science, and Scopus (2010–2023). Ten high-quality studies were analyzed for diagnostic accuracy metrics across multiple NIPT platforms. MPS-based cffDNA NIPT demonstrated pooled sensitivity of 99.3
Microplastics are emerging environmental contaminants with increasing evidence of reproductive toxicity. This study investigated the different effects of polystyrene microplastics (PSµPs) on male reproductive function and evaluated the protective role of taurine (Taur) in Swiss mice using integrated in silico and in vivo approaches. Adult mice were orally exposed to PSµPs (10 mg/kg) for eight weeks, with or without Taur supplementation (200 mg/kg). PSµPs exposure resulted in marked reproductive toxicity, evidenced by significant reductions in gonadosomatic index, testicular weight, and testosterone levels, along with disruption of LH and estradiol balance. Moreover, PSµPs induced severe oxidative stress, as evidenced by significant declines in SOD, CAT, and GPx activities and an increase in MDA levels. At the molecular level, PSµPs caused pronounced downregulation of key steroidogenic genes (STAR, CYP11A1, CYP17A1, CYP19A1, and HSD17B3) compared to controls. Histopathological analysis revealed extensive testicular degeneration, increased apoptosis (elevated cleaved caspase-3), and reduced cell proliferation (decreased PCNA expression). Importantly, Taur co-administration significantly attenuated these adverse effects, restoring antioxidant defenses, partially normalizing hormone levels and gene expression, and improving testicular architecture. In silico docking further supported these findings by demonstrating strong interactions between styrene and the protein products of mRNAs involved in steroidogenesis, suggesting potential binding affinities. Overall, this study highlights that PSµPs induce severe testicular dysfunction through oxidative stress–mediated and gene regulatory mechanisms, while taurine exerts a potent protective effect via antioxidant, anti-apoptotic, and endocrine-modulatory pathways. These findings provide novel insights into microplastic-induced reproductive toxicity and propose taurine as a promising therapeutic strategy.
Polystyrene microplastics (PS-MPs) have recently gained attention as widespread environmental contaminants posing risks to both human and animal health. In this study, we investigated the potential protective effect of taurine (200 mg/kg b.wt) against cardiopulmonary toxicity induced by PS-MPs (10 mg/kg b.wt) in male Swiss mice following a 60-day oral exposure. Molecular docking investigation for both proteins and mRNA targets was carried out utilizing a global, flexible docking strategy that allowed for full ligand conformational freedom and binding surface exploration. We designed an experimental model comprising four groups: Control, Taurine, PS-MPs, and a combined group (PS-MPs + Taurine). The results indicated that taurine significantly protected against PS-MPs-induced biochemical, histopathological, and molecular alterations that occurred in the cardiac and pulmonary tissues of mice. PS-MPs exposure disrupted the redox balance by suppressing enzymatic antioxidants (CAT, SOD, GPx) and increasing lipid peroxidation, while elevating cardiac injury markers (LDH, CK-MB, CPK, cTnI). These oxidative changes were accompanied by increased pro-inflammatory cytokines (TNF-α, IL-1β) in both tissues, histopathological lesions in the heart and lungs, and upregulation of gene expressions of inflammatory and pyroptotic mediators (NLRP3, Caspase-1, ASC, GSDMD, NF-κB, COX-2, IL-1β, IL-18). Co-administration of taurine with PS-MPs markedly ameliorated these alterations, restoring antioxidant defenses, reducing lipid peroxidation and cytokine levels, downregulating inflammasome and pyroptosis-related gene expression, and improving tissue architecture. Molecular docking supported these findings by showing taurine's potential interactions with inflammatory mediators, while styrene exhibited affinity for antioxidant enzymes, consistent with in vivo oxidative disruption. Collectively, the study highlights oxidative stress and inflammation as key mechanisms of PS-MPs-induced cardiopulmonary toxicity and highlights taurine's promise as a protective agent against microplastics-related health risks.
A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) plays critical roles in various cancer-associated biological events, such as cell multiplication, migration, and metastasis. This study employs both the TCGA database and patient samples to demonstrate that ADAM10 is highly expressed in non-small cell lung cancer (NSCLC) compared with normal tissue at different stages. Increased ADAM10 expression is positively correlated with decreased overall and recurrence-free survival. On the functional front, overexpression of ADAM10 promotes lung cancer cell progression, migration, and invasion, whereas downregulation of ADAM10 inhibits these processes. Mechanically, ADAM10 modulates the expression of Notch1, MMP9 and EMT markers such as Vimentin, N-cadherin, and E-cadherin. Overall, our findings suggest that ADAM10 may be a promising therapeutic and prognostic marker for NSCLC, emphasizing the importance of regulating its expression.
Fluctuations in dissolved oxygen (DO) levels in aquaculture systems can induce hypoxia and hypercapnia, leading to physiological disruptions in fish. This study aimed to assess the effectiveness of dietary supplementation with camel whey protein hydrolysate (CWP) in mitigating the effects of hypoxia stress on physiological limits in Oreochromis niloticus. To attain this, firstly, we applied an in silico study to predict the protein–protein interaction of camel’s α-lactalbumin, lactoferrin, and lysozyme with tilapia’s NF-κB, TNF-α, IL-1β, IL-6, and IL-8 via PDBsum Generate. Then we planned for the in vivo trial; 160 obviously healthy Nile tilapia (average16.40 ± 0.40 g) were divided into four groups in four replicates for a 30-day feeding experiment. The control group (normoxic) received a basal diet without supplementation, maintaining DO levels > 90
DHX36 is an ATP-dependent DNA/RNA helicase that unwinds the guanine-quadruplexes (G4s) of DNA or RNA and regulates their metabolism for key biological functions. Breast cancer is a malignant tumor and effective targeted therapy drugs are limited, even though chemotherapy is generally used. In this study, we found that overexpression of DHX36 promotes breast cancer cell growth, migration, and invasion in vitro, while knocking down or knocking out reversed in vitro and in vivo. Moreover, DHX36 was highly expressed in most clinical breast tumor tissues compared with the matched healthy tissues. Accordingly, higher DHX36 expression correlated with poor recurrence-free survival (RFS) in the patients of breast cancer. These results substantiate that DHX36 might be a diagnostic and prognostic biomarker and is a proto-oncogene that promotes the growth and metastasis of breast cancer. Thus, targeting DHX36-associated G4s in genes, particularly in proto-oncogenes, might be a novel anticancer strategy.
Aromatic plants represent a significant source of bioactive compounds and have recently expanded their potential applications in agriculture. In the current study, the essential oil of Salvia rosmarinus (rosemary) was extracted, and its chemical composition was analyzed using gas chromatography-mass spectrometry (GC-MS). Under greenhouse conditions, the antiviral effectiveness of the essential oil against tobacco mosaic virus (TMV) was evaluated on Nicotiana glutinosa, marking the first comprehensive assessment of its impact on plant viruses. A computational analysis of molecular docking interactions was performed to explore the potential interactions of target compounds with the three protein components of TMV. Additionally, the influence of essential oil on the root tips of Allium cepa was assessed for its genotoxic effects. In comparison to untreated infected plants, the curative treatment demonstrated a peak viral inhibition rate of 76.3% at 300 µg/mL, while the protective and inactivation treatments reached maximum rates of 70.7% and 62.8%, respectively, at the same concentration. At elevated concentrations of essential oil (300 µg/mL), the genotoxicity assay showed a concentration-dependent decrease in the mitotic index and an increase in chromosomal abnormalities. The GC-MS analysis revealed that the primary constituents of the essential oil were α-terpineol (19.3%), isoborneol (14.1%), and camphor (13.2%). Furthermore, an in-silico assessment of the candidate phytoconstituents indicated that the antiviral properties are mainly associated with the isoaromadendrene epoxide (0.35%), cubenol (0.22%), epiglobulol (2.06%), caryophyllene (5.73%), and caryophyllene oxide (2.66%) compounds. Thus, we assert that the synergistic properties of oil components account for their significant antiviral efficacy. Overall, the results of our study suggest that rosemary essential oil demonstrates significant antiviral properties and may serve as a promising antiviral agent for combating plant viral infections. Nonetheless, additional field validation and investigations into individual components and their synergistic combinations are essential to comprehend their effectiveness and maximize their application.
Food preservatives can break food safety worldwide; herein, we studied the mitigating effect of Ficus carica (FC) on hepato-renal injury resulting from monosodium glutamate (MSG) or metanil yellow (MY) as a common food preservative. Rats were assigned into five groups; Control, MSG (400 mg/kg), MY (200 mg/kg), FC+MSG (received FC plus MSG), and FC+MY group (received FC plus MY). The antioxidant properties of FC were evaluated. The results revealed the antioxidant potency of FC leave extract. MSG/MY evoked a hepato-renal injury indicated by marked elevations in their biochemical functions. Besides, oxidative damage was also initiated represented by significant increases in MDA levels and decreases in GSH content and SOD activity accompanied by apoptotic cascade (increases in Bax/Bcl2 ratio and caspase3 expression). The molecular docking ascertained the interaction between MSG/MY and cellular antioxidants. However, FC was able to reduce the MSG/MY-induced oxidative stress, apoptosis, and histopathological alterations as well as improve the liver and kidney functions. In the molecular docking model, the natural bioactive compounds of FC explored high affinities for binding with Bax and caspase-3 abrogating the induced apoptosis. The antioxidant potential of FC mitigated the hepato-renal damage in rats caused by MSG or MY.
Bacterial L-glutaminase (L-GLS) has emerged as a potential therapeutic target in cancer treatment by disrupting glutamine-dependent metabolic pathways in tumor cells. This study focused on isolating and characterizing L-GLS-producing marine bacteria from Mediterranean seawater for preliminary therapeutic evaluation. Halomonas aquamarina HBIM1 was identified as the most efficient isolate through comprehensive phenotypic, genotypic, and enzymatic screening. The enzyme was successfully purified, achieving a specific activity of 748.35 U/mg with 3.39-fold purification. SDS-PAGE analysis confirmed high purity with a single 66 kDa protein band. Kinetic characterization revealed optimal activity at pH 8 and 50 °C, with strong substrate affinity (Km = 0.198 mM⁻¹). Preliminary in vitro cytotoxicity screening demonstrated selective antiproliferative effects on HepG2 liver cancer cells (IC50 = 33.98 µg/ml) compared to normal WI-38 cells (IC50 = 93.43 µg/ml), yielding a 2.75-fold selectivity index. Molecular docking analysis identified tannic acid and 6-diazo-5-oxo-L-norleucine as selective inhibitors of bacterial L-GLS, with tannic acid showing the highest binding affinity (-12.25 kcal/mol) and 5-fold selectivity over human L-GLS, suggesting potential for combination therapy strategies. These proof-of-concept findings indicate the preliminary anticancer potential of Halomonas-derived L-GLS and computational support for selective inhibitor development. However, comprehensive preclinical validation, including in vivo efficacy studies, toxicological evaluation, and pharmacological profiling, is essential to establish therapeutic viability and safety before clinical consideration.
Despite adiponectin's recognized anti-inflammatory properties, its impact on cardiovascular homeostasis involves poorly defined mechanisms. We investigated the effect of adiponectin on chemokine-induced cell migration and their potential intermolecular interactions. Our findings revealed that cell migration induced by recombinant PF4, MCP-1, or RANTES in HL-60 cells was significantly inhibited by pre-treating cells with adiponectin. Surface plasmon resonance analysis and molecular docking analysis indicated that only PF4 binds to adiponectin with a higher affinity of adiponectin to the PF4 binding site respectively. These results suggest that adiponectin's atheroprotective functions may be mediated by its ability to reduce PF4-induced monocyte migration through direct interaction.
Thymoquinone (TQ) is a bioactive component derived from Nigella Sativa seeds, and its anticancer properties have been well-documented. Our preliminary studies have also shown that the effective concentration of TQ against breast cancer (BC) is slightly high, indicating a need for chemical modification and optimization of the TQ compound. To address this, we designed and synthesized numerous TQ derivatives and conducted in-depth studies on the 13th derivative, TQFL13 from our laboratory. We found that, in BC cell lines, TQFL13 is more sensitive than that of TQ. The acute toxicity of TQFL13 in mice is significantly lower than that of TQ. We also discovered that TQFL13 impacts the progression of BC by affecting various cellular processes, including growth, invasion, migration, cell cycle, and apoptosis. Furthermore, treatment with TQFL13, it was found to inhibit the growth and metastasis of tumor allograft derived from mouse cancer cells 4 T1, and exhibit lower toxicity compared to TQ. Mechanically, TQFL13 is involved in signaling pathways in cell apoptosis and cell cycles by reducing PARP and BCL-2, CyclinB1, CyclinD1, and p53 levels as well as increasing BAX and phosphorylated p53 (ser15) levels in both BT549 and MDA-MB-231 cells. Taken together, these research findings imply that TQFL13, as a derivative of TQ, exerts a high inhibitory capability on BC cells with lower toxicity than TQ, indicating its potential for practical applications.
Cancer is characterized by abnormal cell growth and remains a leading global cause of death despite advances in conventional therapies. Limitations such as lack of selectivity, cytotoxic side effects, and multidrug resistance underscore the need for potent anticancer agents. Topoisomerase II (TOP2) has emerged as a pivotal target for anticancer drugs, categorized as poisons and catalytic inhibitors. While clinically used TOP2-based drugs predominantly act as poisons, concerns regarding their cytotoxicity and DNA-damaging potential persist. In response to these challenges, exploring natural bioactive compounds (NBCs), including small molecules from Chinese herbs, as sources of novel anticancer agents has become a focal point in pharmaceutical research. Recognizing that NBCs alone may not satisfy as anticancer agents, this review aims to comprehensively analyze the current published studies, specifically focusing on the combined applications of TOP2-inhibiting approved chemotherapeutics and natural products. The review explores this approach's potential synergies and challenges, emphasizing the importance of developing effective and targeted anticancer strategies.
This study aims to develop and evaluate Glycyrrhiza glabra-based magnesium oxide/iron oxide nanocomposite (NC) functionalized with chitosan and curcumin to enhance therapeutic efficacy against lung cancer and oxidative stress. This is the first report integrating G. glabra extract with chitosan and curcumin functionalization into a MgO/Fe2O3 nanocomposite for enhanced antioxidant and anticancer effects. The developed nanocomposite demonstrated strong biocompatibility and in vitro therapeutic efficacy, as evidenced by low cytotoxicity in normal cells and significant inhibitory effects against A549 lung cancer cells. In this study, bioactive phytochemical-loaded G. glabra extract was used as a green capping and reducing agent to synthesize MgO/Fe2O3 NC. The nanomaterials were also functionalized with curcumin and chitosan to promote stability, bioavailability, and site-specific pharmacological activity. The synthesis process was carried out under green conditions, in which the nanocomposite was characterized using FTIR, UV–Vis spectroscopy, EDX analysis, zeta potential analysis, HR-TEM, and XRD. The antioxidant potential was assessed through the DPPH free radical scavenging activity, whereby MgO/Fe2O3–chitosan–curcumin NCs yielded the maximum inhibition of free radicals (IC50 = 0.0977 mg/mL) when compared to other nanomaterials. Antimicrobial activity was assessed against Gram-negative and Gram-positive bacteria, wherein MgO/Fe2O3 NC showed moderate activity, and chitosan and curcumin functionalization reduced this to some extent by possibly controlled release behavior or protection of active sites. Cytotoxicity against A549 human lung cancer cells showed strong inhibition by the MgO/Fe2O3–chitosan–curcumin NC (IC50 = 10 µg/mL), confirmed by changes in morphology in accordance with apoptosis. In addition, in silico ADME simulation suggested favorable bioavailability and low toxicity, which is an indicator of the therapeutic potential of these NCs. To the best of our knowledge, this is the first report on G. glabra-mediated green synthesis with dual functionalization of chitosan and curcumin in a MgO/Fe2O3 nanocomposite. The formulation has synergistic antioxidant and anticancer activity with vast potential in lung cancer therapy. As a whole, the findings address the dual antioxidant and anticancer properties of G. glabra-derived MgO/Fe2O3–chitosan–curcumin NC and their green potential as agents in the treatment of lung cancer. In vivo studies are recommended to confirm efficacy and safety.
The current study evaluated the effects of genistein (GEN) supplementation to alleviate the arsenic (As)-induced hepatotoxicity in Oreochromis niloticus. This was conducted in two steps: a computational prediction study (in silico) and an experimental investigation (in vivo). The prediction step involved molecular docking analysis to assess the interactions between GEN and key stress-related mRNAs in Nile tilapia. In the experimental phase, 160 Nile tilapia fingerlings were randomly assigned to four treatment groups (in four replicates/group) for 60 days: (1) a control group fed a basal diet, (2) a GEN group receiving a GEN-supplemented diet (500 mg/kg), (3) an As group exposed to 10 µg/L As, and (4) an As + GEN group, in which fish was exposed to As and fed the GEN-supplemented diet. The computational assessment of GEN’s binding ability revealed strong interactions with key mRNAs associated with inflammation and misfolded protein responses. The in vivo results revealed that GEN significantly alleviated As-induced hepatic oxidative stress and hepatocellular damage by restoring liver enzyme levels, lipid profiles, and bilirubin content and restoring the serum proteins to near-normal values. Additionally, GEN downregulated the expression of endoplasmic reticulum (ER) stress- and inflammation-related genes in the liver tissue of the As + GEN group, compared to the As-exposed fish fed on a basal diet. Additionally, the histopathological analysis further confirmed that GEN supplementation mitigated hepatic tissue damage, reducing necrosis, congestion, and inflammatory cell infiltration. In conclusion, GEN supplementation effectively counteracted As-induced hepatotoxicity in Nile tilapia by modulating oxidative stress, ER stress, and inflammation while preserving liver structure and function. Also, the molecular docking results suggest that GEN interacts with the mRNAs of inflammatory and misfolded protein targets, which are increased due to exposure to As-contaminated water. All our findings highlight GEN as a promising natural dietary additive for improving hepatic health in fish inhabiting As-contaminated environments.
Fipronil (FPN) is an effective pesticide for veterinary and agricultural use; however, it can induce neurotoxic effects on non-target organisms after accidental exposure. Astaxanthin (AST) is a dark red carotenoid with antioxidant, anti-inflammatory, neuroprotective, and antiapoptotic effects. This study investigated the ameliorative impact of AST against FPN-induced brain damage in rats. Thirty-two adult Wistar rats were allocated into four groups (n = 8): Control, AST (20 mg/kg bwt/day), fipronil (FPN) (20 mg/kg bwt/day), and AST + FPN group. Acetylcholine (ACh), dopamine, malondialdehyde (MDA), and proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and inflammatory cytokine cyclooxygenase-2 (COX2) levels were enhanced in the FPN-administered group relative to the control group. In addition, a substantial reduction of acetylcholine esterase (AchE), gamma-aminobutyric acid (GABA), serotonin, reduced glutathione (GSH) levels, catalase (CAT), and total superoxide dismutase (T-SOD) enzyme activities were determined. FPN induced histopathological alterations in the cerebral and cerebellar tissues. Likewise, the histomorphometric image analysis of H and E-stained tissue sections was constant with FPN-induced neurotoxicity. Immunohistochemically, an intense positive immunohistochemical staining of apoptotic marker caspase-3 and astrocytes activation marker glial fibrillary acidic protein (GFAP) in the examined tissues was noticed. Inversely, the simultaneous administration of AST partially attenuated FPN impacts, ameliorating the severity of FPN-induced neuronal damage. These results were also established with the molecular docking findings. It could be suggested that AST has antioxidant, anti-inflammatory, and anti-apoptotic capabilities against FPN-induced neuronal damage via suppression of oxidative stress and pro-inflammatory cytokines, preservation of the neurotransmitters, and the cerebral and cerebellar histoarchitectures.
The theory of aging is primarily concerned with oxidative stress caused by an imbalance in reactive oxygen species generation and cellular antioxidants. To alleviate the oxidative stress, we investigated the protective effect of diosgenin (DSG) for D-galactose (D-gal) using 20 and 40 mg of DSG/kg/day/orally for 42 days. The findings showed that D-gal caused brain and liver oxidative injuries by upregulating aging and oxidative markers. To counteract the oxidative stress caused by D-gal, DSG upregulated glutathione peroxidase-1, superoxide dismutase-1, and glutathione S-transferase-α. DSG also diminished the expression of p53, p21, Bcl-2-associated X protein, caspase-3, and mammalian target of rapamycin in brain and liver, as well as the build-up of β-galactosidase. DSG, in a dose-dependent manner, decreased the oxidative aging effects of D-gal in brain and liver tissues through targeting of aging and apoptotic marker genes. Finally, it should be noted that consuming DSG supplements is a suggesting natural preventative agent that may counteract aging and preserve health through improvement of body antioxidant status and control aging associated inflammation and cellular apoptosis.
Ginger (Gin) has numerous therapeutic properties. One of Gin’s most potent components is 6-gingerol, a naturally occurring phenol. This study aimed to investigate the therapeutic impact of gingerol and/or sorafenib on the ATG4/CASP3 and COIIV/COX-2/NF-B Expression as a potential therapy for DAB-induced HCC. Gin was administered to HCC mice induced by p-Dimethylaminoazobenzene (DAB) alone or combined with sorafenib (Sor). Superoxide dismutase (SOD), catalase (CAT), and oxidative stress malondialdehyde (MDA), as well as biochemical markers including AST, ALT, ALP, Albumin, and Bilirubin, were examined. The expression of oncogenes (COIIV, COX-2, NF-κB, and survivin) and tumor suppressor genes (ATG4 and CASP3) was evaluated using qPCR. According to the results, the levels of MDA have been markedly decreased, while SOD and CAT have been increased. Further, the expression levels of tumor suppressor genes were upregulated, whereas the expression levels of oncogene genes were downregulated. Furthermore, in a dose-dependent manner, gingerol has shown the potential to alleviate hepatic portal vein (PV) dilatation and could offer a reliable therapy for HCC. This suggests combining the two compounds may be more effective than alone and that Gin could be a promising therapeutic option for HCC. The binding of Gin and Sor to the active sites of the target genes prevents them from functioning normally, which in turn stops the pathways from carrying out their oncogenic functions. Additionally, COX-2 inhibition reduces the production of certain pro-inflammatory compounds, which further averts oncogenesis. Conclusively, this study indicated that Gin has cytoprotective properties and anti-cancer activity that may be related to controlling oxidative stress. This effect may be achieved by suppressing the COIIV/COX-2/NF-κB pathway and upregulating the ATG4 /CASP3 pathways.