Colorectal cancer (CRC) is a prevalent global malignancy with complex etiologies, including microbiota alterations. This study investigates gut microbiota and biofilm-producing bacteria in 35 Thai CRC patients, analyzing paired normal and tumor biopsy samples. Bacterial DNA from the V3-V4 region of 16S rRNA was sequenced, and biofilms were visualized via scanning electron microscopy and fluorescence in situ hybridization (FISH). Results revealed Firmicutes as the dominant phylum, followed by Bacteroidota, Proteobacteria, and Fusobacteriota, with Fusobacteriota and Bacteroidota notably enriched in left-sided CRC. Key biofilm producers-Bacteroides fragilis, Fusobacterium nucleatum, and Pasteurella stomatis-showed significantly higher gene expression in tumor tissues. Dense biofilms and higher Fusobacterium abundance, localized within the crypts of Lieberkuhn, were observed in CRC tissues. These findings highlight CRC-associated microbiota alterations and pathogenic biofilm production, emphasizing a spatial relationship between tumor location and microbial distribution, with potential implications for understanding CRC pathogenesis and therapeutic targeting.

Natural compounds with significant bioactive properties can be found in abundance within biomasses. Especially prominent for their anti-inflammatory, neuroprotective, antibacterial, and antioxidant activities are cinnamic acid derivatives (CAs). Ferulic acid (FA), a widely studied phenylpropanoid, exhibits a broad range of therapeutic and nutraceutical applications, demonstrating antidiabetic, anticancer, antimicrobial, and hepato- and neuroprotective activities. This research investigates the green enzymatic synthesis of innovative and potentially bifunctional prodrug derivatives of FA, designed to enhance solubility and stability profiles. Selective esterification was employed to conjugate FA with xylitol, a biobased polyol recognized for its bioactive antioxidant properties and safety profile. Furthermore, by exploiting t-amyl alcohol as a green solvent, the enzymatic synthesis of the derivative was optimized for reaction parameters including temperature, reaction time, enzyme concentration, and molar ratio. The synthesized derivative, xylitol monoferulate (XMF), represents a novel contribution to the literature. The comprehensive characterization of this compound was achieved using advanced spectroscopic methods, including 1H-NMR, 13C-NMR, COSY, HSQC, and HMBC. This study represents a significant advancement in the enzymatic synthesis of high-value biobased derivatives, demonstrating increased biological activities and setting the stage for future applications in green chemistry and the sustainable production of bioactive compounds.

The honey bee is an important pollinator insect susceptible to environmental contaminants. We investigated the effects of a waste fire event on elemental content, oxidative stress, and metabolic response in bees fed different nutrients (probiotics, Quassia amara, and placebo). The level of the elements was also investigated in honey and beeswax. Our data show a general increase in elemental concentrations in all bee groups after the event; however, the administration of probiotics and Quassia amara help fight oxidative stress in bees. Significantly lower concentrations of Ni, S, and U for honey in the probiotic group and a general and significant decrease in elemental concentrations for beeswax in the probiotic group and Li in the Quassia amara group were observed after the fire waste event. The comparison of the metabolic profiles through pre- and post-event PCA analyses showed that bees treated with different feeds react differently to the environmental event. The greatest differences in metabolic profiles are observed between the placebo-fed bees compared to the others. This study can help to understand how some stress factors can affect the health of bees and to take measures to protect these precious insects.

HBV has a small genome and thrives in the infected hepatocytes by hijacking the cellular machinery and cellular pathways. HBV induces incomplete autophagy for its replication and survival. This study showed that HBV replication induces Reactive oxygen species (ROS) production, which in turn augments the formation of autophagosomes. Augmenter of liver regeneration (ALR) is a sufhydryl oxidase and has an anti-oxidative property. We sought to determine the interplay between HBV and antioxidant protein ALR. We showed that HBV downregulated ALR expression in hepatic cells. There was increased ROS production in HBV-infected cells while ALR downregulated ROS levels and expression of NADPH oxidase NOX4. N-acetyl cysteine, a ROS scavenger, downregulated ROS level and autophagosome formation in HBV-expressing cells. ALR overexpression in HBV-expressing cells downregulated the expression of autophagy marker proteins while upregulated the expression of p-MTOR. ALR overexpression decreased the expression of HBx, HBsAg, and total HBV load. This study showed that HBx relieved ALR-mediated inhibition by upregulating the miR-181a expression in HBV-infected cells, which in turn downregulated ALR expression.

Osteosarcoma (OS), the most prevalent primary malignant bone tumor, is characterized by a poor prognosis and high metastatic potential. Mitochondrial autophagy has been implicated in cancer suppression. This study aimed to identify prognostic genes associated with mitochondrial autophagy in OS. Public datasets, including TARGET-OS, GSE99671, and GSE21257, were retrieved for analysis. Differentially expressed genes (DEGs1) between OS and normal samples were identified from GSE99671. Single-sample Gene Set Enrichment Analysis (ssGSEA) was applied to quantify the enrichment scores of 29 mitochondrial autophagy-related genes (MARGs) in OS samples from TARGET-OS, categorizing them into high- and low-score groups to extract DEGs2. The intersection of DEGs1 and DEGs2 yielded mitochondrial autophagy-associated differentially expressed genes (MDGs). Prognostic genes were subsequently screened through a multi-step regression analysis, and a risk score was computed. TARGET-OS samples were stratified into high- and low-risk groups based on the optimal cutoff value of the risk score. GSEA was conducted between the two risk groups. Additionally, associations between prognostic genes and the immune microenvironment were explored. A total of 31 MDGs were identified from the overlap of 3,207 DEGs1 and 622 DEGs2. Five prognostic genes-KLK2, NRXN1, HES5, OR2W3, and HS3ST4-were further selected. Kaplan-Meier survival analysis indicated significantly reduced survival in the high-risk group. GSEA revealed enrichment in ABC transporter activity and glycolysis/gluconeogenesis pathways. Immunoanalysis demonstrated significant differences in 11 immune cell populations and three immune functions between risk groups, notably myeloid-derived suppressor cells (MDSCs) and Type 1 T helper cells. HS3ST4 exhibited the strongest positive correlation with macrophages, whereas NRXN1 showed the most pronounced negative correlation with memory B cells. Expressions of HAVCR2 and PDCD1LG2 were elevated in the low-risk group. Functional analysis indicated significant differences in dysfunction patterns between risk groups. This study identified five mitochondrial autophagy-related prognostic genes and constructed a risk model, offering novel insights into OS diagnosis and therapeutic strategies.

In this study, we purified and identified antioxidant peptides from equine plasma protein hydrolysates and assessed their protective effects against H2O2-induced oxidative stress in Caco-2 cells. Four antioxidant peptides were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in equine plasma protein hydrolysate, namely: GTMVGC (567.69 Da), FGMTST (662.88 Da), VGYHSHF (847.01 Da) and ALSPFFKE (939.18 Da). Among them, ALSPFFKE showed the strongest antidigestive properties after modelled digestion studies. Moreover, ALSPFFKE enhanced intracellular superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities while significantly reducing reactive oxygen species accumulation and malondialdehyde formation in Caco-2 cells. The molecular docking analysis suggested that ALSPFFKE achieves regulation of the Keap1-Nrf2 pathway mainly by forming multiple hydrogen bonds and hydrophobic interactions with key amino acids (Arg380, Ser555, Gln530, Tyr334) in Keap1. These findings suggested that equine plasma peptides hold significant promise for the development of novel, potent, and stable antioxidant functional foods.

Metabolic disorders and chronic liver disease (CLD) play crucial roles in the development and progression of liver cancer (LC). Since the ethnic minority population increasingly suffers from CLD and LC, it is vital to understand the biosocial factors contributing to CLD and LC. The 'All of Us' database, with significant participation from minority populations, provides a valuable tool for studies in different racial/ethnic groups. Using different databases, including the 'All of Us' and 'The Cancer Genome Atlas', this study aimed to understand the biosocial factors contributing to CLD and LC.

Using 'All of Us' data, confounding factors like the lack of immunization, comorbidities, and socioeconomic status (SES) barriers were analyzed in a cohort of 33767 CLD [non-alcoholic fatty liver disease, alcoholic liver disease, and Hepatitis B and C] patients. Among the 556 LC patients in the 'All of Us' database, 92% had CLD. Since hypoxanthine is known to be increased in the urine of LC patients, purine metabolic pathway genes were analyzed using different databases and validated using publicly available RNASeq data.

We identified several confounding factors associated with CLD in Hispanic (HA) and African American (AA) populations compared to the non-Hispanic White (NHW) populations. HA and AA CLD patients suffer from high SES barriers. While most of the genes related to the purine metabolic pathway were upregulated in LC, xanthine dehydrogenase (XDH), which converts hypoxanthine to uric acid, showed a downregulation in the tumor compared to the normal tissues. The TCGA data among different racial/ethnic groups showed that only in Asian (AN) LC tumors the XDH expression was significantly lower compared to the NHW. The decreased XDH mRNA expression in AN LC compared to benign tissues was further validated using publicly available RNAseq datasets. Survival analysis confirmed poor overall survival among the AN LC patients with lower XDH expression in their tumors.

Our study identified several confounding factors contributing to the minority CLD population. This study also identified decreased XDH expression as a critical metabolic alteration that has clinical significance in AN LC patients.

The KIT receptor is a transmembrane protein found on the surface of many different cell types. Mutant forms of KIT are drivers of myeloid neoplasms, including systemic mastocytosis. The KIT D816V mutation is the most common, leading to constitutive activation of the receptor and its downstream targets, and it is highly resistant to c-KIT inhibitors. Metabolic rewiring is a common trait in cancer. We analyzed the metabolic profile induced by the KIT D816 mutation, measuring mitochondrial parameters in two myeloid cell lines. We found that the KIT D816V mutation causes a significant increase in mitochondrial abundance and activity associated with superoxide production, which could promote DNA instability. Functional and morphologic changes in mitochondria were associated with reduced levels of BNIP3 protein expression. We also detected low BNIP3 levels in clinical acute myeloid leukemia samples harboring D816V mutations. In addition, we have found constitutive mTOR activation in mutated cells, a pathway that has been shown to regulate autophagy. Our data suggest that KIT D816V increases mitochondrial activity through downregulation of BNIP3 expression, which increases mitochondrial number through the autophagy pathway. Alterations in the cellular metabolism induced by the KIT D816V mutation could be therapeutically exploited.

The pathogenesis of type 1 diabetes (T1D) involves a complex interplay of genetic predisposition, immune processes, and environmental factors, leading to the selective destruction of pancreatic beta-cells by the immune system. Emerging evidence suggests that intrinsic beta-cell factors, including oxidative stress and post-translational modifications (PTM) of beta-cell antigens, may also contribute to their immunogenicity, shedding new light on the multifaceted pathogenesis of T1D. Over the past 30 years, neoepitopes generated by PTMs have been hypothesized to play a role in T1D pathogenesis, but their involvement has only been systematically investigated in recent years. In this review, we explored the interplay between oxidative PTMs, neoepitopes, and T1D, highlighting oxidative stress as a pivotal factor in immune system dysfunction, beta-cell vulnerability, and disease onset.

While genomic alterations are fundamental to biological evolution, enabling adaptation and diversity, they can also result in detrimental outcomes, such as the development of genetic diseases including cancer. The budding yeast Saccharomyces cerevisiae serves as an exemplary model for investigating the mechanisms behind various genomic alterations, including point mutations, chromosomal rearrangements, and whole-chromosome aneuploidy. In this review, we highlight the application of genetic screening systems to assess the mutagenic effects of physical and chemical agents efficiently. Additionally, we discuss the utilization of high-throughput sequencing technologies to uncover comprehensive genomic alterations and rare genetic events. We provide a detailed summary of the features of genomic alterations and discuss the genetic mechanisms driving these changes under both spontaneous and stress-induced conditions. Given the high conservation of DNA replication and repair machinery across different organisms, the insights gained from studies on yeast offer valuable perspectives for understanding the delicate balance between genome plasticity and integrity in other species.

Oxidative stress is a key component of many diseases, including neurodegenerative diseases such as Alzheimer's disease. Reactive oxygen species (ROS) such as hydrogen peroxide and nitric oxide lead to disease progression by binding to proteins and causing their dysregulation. Metallothionein-3 (MT3), a cysteine-rich brain-located metalloprotein, has been proposed to be a key player in controlling oxidative stress in the central nervous system. We report data from a combination of electrospray ionization mass spectrometry (ESI-MS), ultraviolet (UV)-visible absorption spectroscopy, and circular dichroism spectroscopy that identify the oxidation pathway of MT3 fully bound to endogenous Zn(II) or exogenous Cd(II) together with the partially metalated species. We characterize the intermediate species formed during the oxidation of MT3, which is dominated by disulfide bond formation. We report the rates of oxidation. For both fully and partially metalated MT3, MT3 is oxidized at 5 to 10 times the rate of MT1, a similar but kidney-expressed isoform of MT. As oxidation progresses, MT3 follows a domain-specific demetallation pathway when it is fully metalated, and a domain-independent pathway when partially metalated. This suggests the presence of a significant susceptibility toward oxidation when MT3 is partially metalated, and, therefore, a possible protective role of Zn(II) when fully metalated. With the evidence for the rapid oxidation rate, our data support the proposals of MT3 as a key antioxidant in physiology.

In this work the relationship between Schistosoma mansoni (Sm) and the induction and progression of colorectal cancer (CRC) is examined. Various clinical studies reviewed here yield inconsistent results, with some reporting no association between Sm infection and CRC and others suggesting a probable to strong association. Here we propose a number of plausible mechanisms whereby Sm infection might contribute to CRC induction and/or progression. These factors are (1) chronic inflammation, (2) exposure to parasite linked antigens and genotoxic products, especially soluble egg antigens (SEAs) and (3) alteration of the intestinal microbiota. These factors probably predispose humans towards CRC and can help in CRC progression however only widespread epidemiological, clinical and pathological studies can firmly establish their role or a complete lack of it.

Free radicals, characterized by the presence of unpaired electrons, are highly reactive species that play a significant role in human health. These molecules can be generated through various endogenous processes, such as mitochondrial respiration and immune cell activation, as well as exogenous sources, including radiation, pollution, and smoking. While free radicals are essential for certain physiological processes, such as cell signaling and immune defense, their overproduction can disrupt the delicate balance between oxidants and antioxidants, leading to oxidative stress. Oxidative stress results in the damage of critical biomolecules like DNA, proteins, and lipids, contributing to the pathogenesis of various diseases. Chronic conditions such as cancer, cardiovascular diseases, neurodegenerative disorders, and inflammatory diseases have been strongly associated with the harmful effects of free radicals. This review provides a comprehensive overview of the characteristics and types of free radicals, their mechanisms of formation, and biological impacts. Additionally, we explore natural compounds and extracts studied for their antioxidant properties, offering potential therapeutic avenues for managing free radical-induced damage. Future research directions are also discussed to advance our understanding and treatment of free radical-associated diseases.

Oxidative stress is universal to all cell types, including cancer. It is elicited by a surplus of reactive oxygen species (ROS) or a reduced cellular ability to defend against those. At low levels (oxidative eustress), this induces altered cellular signaling, while at higher levels (oxidative distress), cellular toxicity and non-specific redox signaling become apparent. While oxidation-induced cell death is a hallmark of many cancer therapies, including ROS-producing radiotherapy, some chemotherapies and targeted therapies, photodynamic therapy, and recently emerging physical modalities such as medical gas plasma (a multi-ROS generating technology), less is known about the transcriptional profiles predisposing cancer cells to oxidative demise. In particular, which genes are associated with resistance or sensitivity to ROS overload and subsequent toxicity has not been systematically investigated. Moreover, it is unclear if there are differences between oxidant types, such as hydrogen peroxide and hypochlorous acid. To this end, we here employed 35 cell lines of various origins (e.g., adenocarcinoma, melanoma, leukemia, squamous cell carcinoma, and neuroblastoma). We first performed in-house transcriptomic analysis to assess baseline transcriptional profiles. Second, all cell lines were exposed to four different ROS concentrations of either hydrogen peroxide, hypochlorous, or gas plasma exposure. Third, correlation analysis was performed to identify genes associated with (i) oxidative stress sensitivity, (ii) oxidative stress resistance, and (iii) similarities and/or differences between the different oxidative stress inducers. Intriguingly, distinct gene sets were found for all treatments, and there was a striking difference between hydrogen peroxide and hypochlorous acid, suggesting different modes of action of both oxidants.

Water pollution, oxidative stress and the emergence of multidrug-resistant bacterial strains are significant global threats that require urgent attention to protect human health. Nanocomposites that combine multiple metal oxides with carbon-based materials have garnered significant attention due to their synergistic physicochemical properties and versatile applications in both environmental and biomedical fields. In this context, the present study was aimed at synthesizing a ternary metal-oxide nanocomposite consisting of silver oxide, copper oxide, and zinc oxide (ACZ-NC), along with a multi-walled carbon nanotubes modified ternary metal-oxide nanocomposite (MWCNTs@ACZ-NC). The properties of the synthesized nanomaterials were characterized using Fourier transform infrared (FT-IR) spectroscopy, field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), and energy dispersive X-ray (EDX) spectroscopy. The results obtained suggested the successful synthesis of both samples, as evidenced by the morphological changes observed in the SEM images, a transmittance band at 748.02 cm-1 in the FT-IR spectrum, and a diffraction peak at 44.39° in the XRD pattern. The band gap energies were determined via diffuse reflectance spectroscopy (DRS), with a redshift observed in the absorbance edge upon the incorporation of MWCNTs. The synthesized samples were tested as photocatalysts for the degradation of rhodamine 6G (Rh-6G), with the highest degradation efficiency (99.61%) achieved by MWCNTs@ACZ-NC. Additionally, the materials were evaluated for their biological activity as antibacterial and antioxidant agents. The MWCNTs@ACZ-NC exhibited the highest antioxidant potential with an IC50 value of 59.22 μg mL-1. However, the incorporation of MWCNTs resulted in a decrease in antibacterial activity, which may be attributed to the blocking of binding sites.

Cancer is one of the serious diseases of modern times, occurring in all parts of the world and shows a wide range of effects on the human body. Reactive Oxygen Species (ROS) such as oxide and superoxide ions have both advantages and disadvantages during the progression of cancer, dependent on their concentration. It is a necessary part of the normal cellular mechanisms. Changes in its normal level can cause oncogenesis and other relatable problems. Metastasis can also be controlled by ROS levels in the tumor cells, which can be prevented by the use of antioxidants. However, ROS is also used for the initiation of apoptosis in cells by different mediators. There exists a cycle between the production of oxygen reactive species, their effect on the genes, role of mitochondria and the progression of tumors. ROS levels cause DNA damage by the oxidation process, gene damage, altered expression of the genes and signalling mechanisms. They finally lead to mitochondrial disability and mutations, resulting in cancer. This review summarizes the important role and activity of ROS in developing different types of cancers like cervical, gastric, bladder, liver, colorectal and ovarian cancers.

Atrial fibrillation (AF) and cancer are increasingly recognized as interrelated conditions, with cancer patients showing elevated incidences of AF, and there is evidence that AF may sometimes precede cancer diagnoses. This comprehensive review investigates the epidemiology, pathophysiology, and management challenges associated with AF in cancer patients. Epidemiologically, several cancers are more closely related to increased rates of AF, including lung, colorectal, gastrointestinal, and hematologic malignancies. Mechanistically, both AF and cancer share pathophysiological pathways centered on inflammation, oxidative stress, and common cardiovascular risk factors, such as hypertension, obesity, and diabetes. The inflammatory microenvironment in tumors, marked by increased cytokines and growth factors, promotes atrial remodeling and AF susceptibility. Elevated reactive oxygen species (ROS) levels, driven by the metabolic demands of cancer, further contribute to atrial fibrosis and structural changes. Moreover, many anticancer treatments exacerbate AF risk. Management of AF in cancer patients presents many unique challenges and requires a multidisciplinary approach. Rate and rhythm control strategies are complicated by potential drug-drug interactions and limited data surrounding early implementation of rhythm control strategies in cancer patients. Interventional approaches such as catheter ablation, though effective in maintaining sinus rhythm, carry significant perioperative risk in patients with malignancy. Stroke prevention with anticoagulants is essential but requires cautious administration to avoid heightened bleeding risks, particularly in patients undergoing chemotherapy. Further, the limited applicability of standard risk stratification tools like CHA2DS2-VASc in this population complicate decisions regarding anticoagulation. This review highlights the bidirectional relationship between AF and cancer, the difficulties in management, and the critical need for further research in this field.

TCIPP (tris(1,3-dichloro-2-propyl) phosphate) and TCEP (tris(2-chloroethyl) phosphate) are organophosphate ester flame retardants found in various consumer products, posing significant health and environmental risks through inhalation, ingestion, and dermal exposure. Research reveals these compounds cause oxidative stress, inflammation, endocrine disruption, genotoxicity, neurotoxicity, and potentially hepatotoxicity, nephrotoxicity, cardiotoxicity, developmental, reproductive, and immunotoxicity. This review summarizes the current knowledge on the toxicological mechanisms of TCIPP and TCEP and presents the latest data on their toxicological effects obtained in vitro and in vivo, using omic systems, and on the basis of computational modelling. It also elaborates on the scope of further toxicities and highlights the necessity of ongoing mechanistic research, integration of new technologies, and successful transfer of the acquired knowledge into risk evaluation, policies and regulations, and the creation of safer products. Since flame retardants are already present in homes, schools, offices, and daycare centres, efforts to scale back the exposure to these chemicals, most especially the hazardous ones, must be made to protect human health and the environment. Therefore, effective and timely prevention, based upon a deep knowledge of the entire toxicological profile of these substances, is the only way to face this difficult toxicological issue and provide for a healthy and safe future.

Extended application of intracanal medicaments such as calcium hydroxide (CH) and triple antibiotic paste (TAP) is documented to reduce dentin's resistance to fracture.

This study intended to evaluate the resistance to fracture of root dentin treated with different medicaments - CH, TAP, CH with chlorhexidine (CHX) and lycopene (LP), and chitosan acetate (CA) - over 7, 14, and 42 days.

Seventy-five single-rooted human mandibular premolars were biomechanically prepared and categorized into five groups based on the medicament used, with further subdivision based on application duration. Fracture resistance was tested after each time interval.

Within-group comparisons were analyzed using repeated measures analysis of variance (ANOVA), while inter-group comparisons used a one-way ANOVA test at a 5% significance level.

At 7 days, no statistically notable differences were found among the groups. However, by day 14 and day 42, the groups treated with CH and TAP exhibited significantly reduced fracture resistance compared to the other groups.

Combining LP with CH and CHX, or using CA, did not reduce radicular dentin fracture resistance, unlike TAP and CH. These findings suggest LP and CA as viable alternatives, potentially minimizing the adverse effects of traditional treatments.

Methotrexate (MTX) is commonly employed in cancer treatment, but its clinical use is restricted due to the MTX-associated renal injury. This study investigates the combined potential of Rhus coriaria (sumac) and bone marrow mesenchymal stem cells (BMMSCs) against MTX-induced nephrotoxicity in rats. The high-resolution-liquid chromatography-mass spectrometry (HR-LC-MS) of sumac extract tentatively identified 22 phytochemicals, mostly flavonoids, anthocyanins, and steroids. Preparation of sumac liposomes attained a suitable particle size of 3041.33 ± 339.42 nm, a polydispersity index of 0.208 ± 0.086, and an encapsulation efficiency of 84.92 ± 3.47%. Rat BMMSCs were injected into the tail vein of the experimental rats (0.5 × 106 cells, intravenous [iv]) of seven treated groups. The experimental design relies on either pre- or posttreatment of rats with intraperitoneal (IP) sumac liposomes (SL) (200 mg/kg, daily with a dose of MTX (300 µg/kg/14 days). The histopathological examination and serum analysis of creatinine and urea revealed good results, besides regulating levels of oxidative stress and inflammatory markers. Additionally, a significant decrease in the gene expression levels of B-Cell Lymphoma 2 (Bcl-2) and caspases-3 and -9, a remarkable increase in the Bcl-2 Associated X-Protein (Bax), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme-oxygenase 1 expression, and a downregulation of Kelch-like ECH-associated protein 1 (Keap1). Collectively, the coadministration of SL with BMMSCs might be a potent therapeutic strategy for attenuation of MTX-induced renal damage. The network pharmacology analysis identified the involved key hub genes as KEAP1, Nrf2, HMOX1, mitogen-activated protein kinase (MAPK1), nuclear factor-kappa B (NF-KB), interleukin-1 beta (IL-1B), and caspase-3. The docking results revealed strong binding affinities of 7-O-methyl-cyanidin-3-O-(2″-galloyl)-galactoside with Keap1 and amentoflavone with MAPK. These insights pave the way for future experimental validation and therapeutic development of sumac-based phytoconstituents against MTX-induced nephrotoxicity.

Recent evidence has proved that resveratrol as a natural polyphenol has great anti-cancer and anti-proliferative effects in cancer cells. In this study, we aimed to examine the protective effects of resveratrol in rats with 1,2-dimethylhydrazine (DMH)-induced colorectal cancer and investigate the potential underlying molecular mechanisms. Male Wistar rats were classified into different groups, including Group 1 without any intervention, group 2 as resveratrol-received rats (8 mg/kg), Group 3 as DMH-received rats, and Group 4, as DMH and resveratrol-received rats. DNA damage, DNA repair, the expression levels and activities of antioxidants, and JNK signaling were evaluated in colon tissues. We found that DNA damage and DNA repair were significantly suppressed and induced, respectively, in DMH + resveratrol groups. The expression levels and activities of antioxidants were increased in DMH + resveratrol groups. Lipid and protein peroxidation were significantly suppressed in DMH + resveratrol groups. In addition, resveratrol also modulated JNK signaling in DMH + resveratrol groups. Our findings demonstrated that resveratrol effectively reversed DMH-mediated oxidative stress and DNA damage by targeting the JNK signaling pathway.

Hepatocellular carcinoma (HCC) often arises in the cirrhotic livers, highlighting the intricate link between hepatic fibrosis and carcinogenesis. Reactive oxygen species produced by NADPH oxidase 4 (NOX4) contribute to liver injury leading to hepatic fibrosis. Paradoxically, NOX4 is known to inhibit HCC progression. This study aims to elucidate the role of NOX4 in hepatocarcinogenesis in the background of hepatic fibrosis. We established the mouse model of HCC arising from the fibrotic liver by administering diethylnitrosamine and carbon tetrachloride to wild-type (WT) or NOX4-/- mice. Hepatic fibrogenesis, tumorigenesis, and macrophage polarization were assessed by immunohistochemistry, PCR, and flow cytometry using in vivo and in vitro models. In NOX4-/- mice, hepatic fibrosis was attenuated, while the number of tumors and the proliferation of HCC cells were increased compared to WT mice. Notably, a significant increase in M2-polarized macrophages was observed in NOX4-/- mice through immunohistochemistry and PCR analysis. Subsequent experiments demonstrated that NOX4-silenced HCC cells promote macrophage polarization toward M2. In addition to attenuating hepatic fibrogenesis, NOX4 deficiency triggers macrophage polarization towards the M2 phenotype in the fibrotic liver, thereby promoting hepatocellular carcinogenesis. These findings provide novel insights into the mechanism of NOX4-mediated tumor suppression in HCC arising from fibrotic livers.

A prevalence of cigarette smoking can cause the accumulation of cadmium (Cd2+) in the lungs, kidneys, and blood. The effects of exposure can cause multiple chronic disease types to emerge in the affected organ systems. The only moderately effective therapeutic option is chelation therapy; the health risks associated with this therapy have caused much criticism. The disease types associated with Cd2+ toxicity have inflammatory components and greatly impact innate immunity. These factors are affected at the cellular level and cause pathways like apoptosis, pyroptosis, and necroptosis. A development in understanding these pathways stipulates that these three pathways act as one complex of pathways, known together as PANoptosis. The inflammatory mechanisms of PANoptosis are particularly interesting in Cd2+ toxicity due to its inflammatory effects. Proteins in the gasdermin family act to release inflammatory cytokines, like interleukin-1β, into the extracellular environment. Cytokines cause inflammatory disease pathologies like fibrosis and cancer. RAW 264.7 monocytes are key in the murine immune system and provide an excellent model to investigate Cd2+ toxicity. Exposure of 0-15 µM CdCl2 was sufficient to increase expression of cleaved gasdermin D (GSDMD) and gasdermin E (GSDME) in this cell type. Cd2+ also exhibits a dose-dependent cytotoxicity in this cell type.

Accidental exposure to high-dose radiation while pregnant has shown significant negative effects on the developing fetus. One fetal organ which has been studied is the placenta. The placenta performs all essential functions for fetal development, including nutrition, respiration, waste excretion, endocrine communication, and immunological functions. Improper placental development can lead to complications during pregnancy, as well as the occurrence of intrauterine growth-restricted (IUGR) offspring. IUGR is one of the leading indicators of fetal programming, classified as an improper uterine environment leading to the predisposition of diseases within the offspring. With numerous studies examining fetal programming, there remains a significant gap in understanding the placenta's role in irradiation-induced fetal programming. This review aims to synthesize current knowledge on how irradiation affects placental function to guide future research directions. This review provides a comprehensive overview of placental biology, including its development, structure, and function, and summarizes the placenta's role in fetal programming, with a focus on the impact of radiation on placental biology. Taken together, this review demonstrates that fetal radiation exposure causes placental degradation and immune function dysregulation. Given the placenta's crucial role in fetal development, understanding its impact on irradiation-induced IUGR is essential.

Ischemia-reperfusion (IR) or reoxygenation injury is the paradoxical exacerbation of cellular impairment following restoration of blood flow after a period of ischemia during surgical procedures or other conditions. Acute interruption of blood supply to the liver and subsequent reperfusion can result in hepatocyte injury, apoptosis, and necrosis. Since the liver requires a continuous supply of oxygen for many biochemical reactions, any obstruction of blood flow can rapidly lead to hepatic hypoxia, which could quickly progress to absolute anoxia. Reoxygenation results in the increased generation of reactive oxygen species and oxidative stress, which lead to the enhanced production of proinflammatory cytokines, chemokines, and other signaling molecules. Consequent acute inflammatory cascades lead to significant impairment of hepatocytes and nonparenchymal cells. Furthermore, the expression of several vascular growth factors results in the heterogeneous closure of numerous hepatic sinusoids, which leads to reduced oxygen supply in certain areas of the liver even after reperfusion. Therefore, it is vital to identify appropriate therapeutic modalities to mitigate hepatic IR injury and subsequent tissue damage. This review covers all the major aspects of cellular and molecular mechanisms underlying the pathogenesis of hepatic ischemia-reperfusion injury, with special emphasis on oxidative stress, associated inflammation and complications, and prospective therapeutic approaches.

Dietary intervention is considered a safe preventive strategy to slow down aging. This study aimed to evaluate the protective effects of a commercially available supplement and six simpler formulations against DNA damage in 3D human keratinocytes. The ingredients used are well known and were combined into various formulations to test their potential anti-aging properties. Firstly, we determined the formulations' safe concentration by evaluating cytotoxicity and cell viability through spectrophotometric assays. We then examined the presence of tumor p53 binding protein 1 and phosphorylated histone H2AX foci, which are markers of genotoxicity. The foci count revealed that a 24-h treatment with the supplement did not induce DNA damage, and significantly reduced DNA damage in cells exposed to neocarzinostatin for 2 h. Three of the simpler formulations showed similar results. Moreover, the antioxidant activity was tested using a recently developed whole cell-based chemiluminescent bioassay; results showed that a 24-h treatment with the supplement and three simpler formulations significantly reduced intracellular H2O2 after pro-oxidant injury, thus suggesting their possible antiaging effect. This study's originality lies in the use of a 3D human keratinocyte cell model and a combination of natural ingredients targeting DNA damage and oxidative stress, providing a robust evaluation of their anti-aging potential.

Reactive oxygen species (ROS) are widely regarded as signaling molecules and play essential roles in various cellular processes, but when present in excess, they can lead to oxidative stress (OS). Growing evidence suggests that the OS plays a critical role in the pathogenesis of HIV infection and is associated with several comorbidities in HIV-infected individuals. ROS, generated both naturally during mitochondrial oxidative metabolism and as a response to various cellular processes, can trigger host antiviral responses but can also promote viral replication. While the multifaceted roles of ROS in HIV pathophysiology clearly need more investigation, this review paper unravels the mechanisms of OS generation in the context of HIV infections, offering insights into HIV viral protein-mediated and antiretroviral therapy-generated OS. Though the viral protein Tat is significantly attributed to the endogenous cellular increase in ROS post HIV infection, this paper sums up the contribution of other viral proteins in HIV-mediated elicitation of ROS. Given the investigations recognizing the significant role of ROS in the onset and progression of diverse pathologies, the paper also explores the critical function of ROS in the mediation of an of array of pathologies associated with HIV infection and retroviral therapy. HIV patients are observed with disruption to the antioxidant defense system, the antioxidant therapy is gaining focus as a potential therapeutic intervention and is well discussed. While ROS play a significant role in the HIV scenario, further exploratory studies are imperative to identifying alternative therapeutic strategies that could mitigate the toxicities and pathologies associated with ART-induced OS.

Assessing oxidative stress is vital in managing type 2 diabetes mellitus (T2DM) and its complications. This systematic review aims to identify the most important oxidative stress markers in T2DM patients and predict associated complications. A literature search was conducted from 2013 to 2023, focusing on case-control, cohort, cross-sectional, and randomized control trials. The included studies had open access and scientific methodologies for assessing oxidative stress markers, while the excluded studies were not published in English or lacked primary objectives related to oxidative stress markers and T2DM or its complications. The quality of eligible studies was evaluated using the Newcastle-Ottawa Scale (NOS) for case-control, cohort, and cross-sectional studies and the Jadad Scale for RCTs. Eighteen studies were selected for the review and 25 potential markers like malondialdehyde (MDA), 11 thiobarbituric acid reactive substances (TBARS), 8-hydroxydeoxyguanosine (8-OHdG), glutathione (GSH), superoxide dismutase (SOD), and isoprostanes were found to be the most commonly used markers to assess oxidative stress in T2DM. These markers help to assess oxidative stress levels in T2DM individuals as well as correlate with diabetic complications. Therefore, assessment and understanding of the role of oxidative stress in T2DM pathophysiology are crucial for improving patient care and mitigating complications.

Arthrobotrys oligospora is a typical nematode-trapping (NT) fungus, which can secrete food cues to lure, capture, and digest nematodes by triggering the production of adhesive networks (traps). Based on genomic and proteomic analyses, multiple pathogenic genes and proteins involved in trap formation have been characterized; however, there are numerous uncharacterized genes that play important roles in trap formation. The functional studies of these unknown genes are helpful in systematically elucidating the complex interactions between A. oligospora and nematode hosts. In this study, we screened the gene AOL_s00004g24 (Ao4g24). This gene is similar to the SWI/SNF chromatin remodeling complex, which was found to play a potential role in trap formation in our previous transcriptome analysis. Here, we characterized the function of Ao4g24 by gene disruption, phenotypic analysis, and metabolomics. The deletion of Ao4g24 led to a remarkable decrease in conidia yield, trap formation, and secondary metabolites. Meanwhile, the absence of Ao4g24 influenced the mitochondrial membrane potential, ATP content, autophagy, ROS level, and stress response. These results indicate that Ao4g24 has crucial functions in sporulation, trap formation, and pathogenicity in NT fungi. Our study provides a reference for understanding the role of unidentified genes in mycelium growth and trap formation in NT fungi.

Colorectal cancer (CRC) is one of the most common cancers worldwide, ranking third in terms of incidence and second as a cause of cancer-related death. There is growing scientific evidence that the gut microbiota plays a key role in the initiation and development of CRC. Specific bacterial species and complex microbial communities contribute directly to CRC pathogenesis by promoting the neoplastic transformation of intestinal epithelial cells or indirectly through their interaction with the host immune system. As a result, a protumoural and immunosuppressive environment is created conducive to CRC development. On the other hand, certain bacteria in the gut microbiota contribute to protection against CRC. In this chapter, we analysed the relationship of the gut microbiota to CRC and the associations identified with specific bacteria. Microbiota plays a key role in CRC through various mechanisms, such as increased intestinal permeability, inflammation and immune system dysregulation, biofilm formation, genotoxin production, virulence factors and oxidative stress. Exploring the interaction between gut microbiota and tumourigenesis is essential for developing innovative therapeutic approaches in the fight against CRC.

Sixteen novel antioxidant peptides from Asian swamp eel (ASE) were identified in previous studies. However, their chemical and cellular antioxidant mechanisms remain unclear. Molecular docking of these peptides with ABTS and DPPH radicals revealed the critical role of hydrogen bonding and Pi-Pi stacking hydrophobic interactions between hydrophobic amino acid residues and free radicals. Residues, such as tryptophan, proline, leucine, and valine, played significant roles in these interactions. All these peptides exhibited notable erythrocyte morphoprotective effects in a model of AAPH-induced oxidative damage of human erythrocytes. Erythrocyte hemolysis was reduced primarily through the modulation of both non-enzymatic (GSH/GSSG) and enzymatic antioxidant systems (SOD, CAT, and GSH-Px) by these peptides. A decrease in levels of MDA, LDH release, and hemoglobin oxidation was observed. Among the peptides, VLYPW demonstrated superior chemical and cellular antioxidant activities, which may be attributed to its higher levels of tyrosine and tryptophan, as well as to its increased hydrophobic amino acid content.

Glioblastoma (GBM) is an aggressive brain cancer characterized by significant molecular and cellular heterogeneity, which complicates treatment efforts. Current standard therapies, including surgical resection, radiation, and temozolomide (TMZ) chemotherapy, often fail to achieve long-term remission due to tumor recurrence and resistance. A pro-oxidant environment is involved in glioma progression, with oxidative stress contributing to the genetic instability that leads to gliomagenesis. Evaluating pro-oxidant therapies in brain tumors is crucial due to their potential to selectively target and eradicate cancer cells by exploiting the elevated oxidative stress levels inherent in these malignant cells, thereby offering a novel and effective strategy for overcoming resistance to conventional therapies. This study investigates the therapeutic potential of doxorubicin (DOX) and photodynamic therapy (PDT) with Me-ALA, focusing on their effects on redox homeostasis. Basal ROS levels and antioxidant gene expression (NFE2L2, CAT, GSR) were quantitatively assessed across GBM cell lines, revealing significant variability probably linked to genetic differences. DOX and PDT treatments, both individually and in combination, were analyzed for their efficacy in inducing oxidative stress and cytotoxicity. An in silico analysis further explored the relationship between gene mutations and oxidative stress in GBM patients, providing insights into the molecular mechanisms underlying treatment responses. Our findings suggest that pro-oxidant therapies, such as DOX and PDT in combination, could selectively target GBM cells, highlighting a promising avenue for improving therapeutic outcomes in GBM.

Reactive oxygen species (ROS) are critical for cellular signaling. Various pathophysiological conditions are also associated with elevated levels of ROS. Hence, ROS-sensitive triggers have been extensively used for selective payload delivery. Such applications are predicated on two key functions: (1) a sufficient magnitude of concentration difference for the interested ROS between normal tissue/cells and intended sites and (2) appropriate reaction kinetics to ensure a sufficient level of selectivity for payload release. Further, ROS refers to a group of species with varying reactivity, which should not be viewed as a uniform group. In this review, we critically analyze data on the concentrations of different ROS species under various pathophysiological conditions and examine how reaction kinetics affect the success of ROS-sensitive linker chemistry. Further, we discuss different ROS linker chemistry in the context of their applications in drug delivery and imaging. This review brings new insights into research in ROS-triggered delivery, highlights factors to consider in maximizing the chance for success and discusses pitfalls to avoid.

Benzothiazole (BTH), benzotriazole (BTR), and their respective derivatives (BTHs and BTRs) are emerging environmental pollutants with widespread human exposure and oncogenic potential. Studies have demonstrated adverse effects of exposure to certain BTHs and BTRs on the respiratory system. However, no study has examined the associations between exposure to BTHs and BTRs and lung cancer risk. We aimed to examine the associations between urinary concentrations of BTHs and BTRs and the risk of lung cancer in the general population from Quzhou, China. We conducted a nested case-control study in an ongoing prospective Quzhou Environmental Exposure and Human Health (QEEHH) cohort, involving 20, 694 participants who provided urine samples during April 2019-July 2020. With monthly follow-up until November 2022, 212 lung cancer cases were recruited and 1:1 matched with healthy controls based on age and sex. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of lung cancer risk associated with urinary BTHs and BTRs concentrations using conditional logistic regression models after controlling for potential covariates. We also examined effect modification by several covariates, including sex, socioeconomic status, smoking status, alcohol consumption, and dietary habit. Creatinine-corrected urinary BTH and 2-hydroxy-benzothiazole (2-OH-BTH) levels were significantly associated with the risk of lung cancer, after adjusting for a variety of covariates. Participants in the highest quartile of BTH had a 95% higher risk of lung cancer, compared with those in the lowest quartile (adjusted OR = 1.95, 95% CI: 1.08-3.49; p for trend = 0.01). Participants with higher levels of urinary 2-OH-BTH had an 83% higher risk of lung cancer than those with lower levels (adjusted OR = 1.83, 95% CI: 1.16-2.88; p for trend = 0.01). Exposure to elevated levels of BTH and 2-OH-BTH may be associated with an increased risk of lung cancer. These associations were not modified by socio-demographic characteristics.

Atmospheric nonthermal plasma (ANTP) has rapidly evolved as an innovative tool in biomedicine with various applications, especially in treating skin diseases. In particular, the formation of reactive oxygen species (ROS) and nitrogen species (RNS), which are generated by ANTP, plays an important role in the biological signaling pathways of human cells. Unfortunately, excessive amounts of these reactive species significantly result in cellular damage and cell death induction. To ensure the safe application of ANTP, preclinical in vitro studies must be conducted before proceeding to in vivo or clinical trials involving humans. Our study aimed to investigate adverse effects on genetic substances in murine fibroblast cells exposed to ANTP. Cell viability and proliferation were markedly reduced after exposing the cells with plasma. Both extracellular and intracellular reactive species, especially RNS, were significantly increased upon plasma exposure in the culture medium and the cells. Notably, significant DNA damage in the cells was observed in the cells exposed to plasma. However, plasma was not classified as a mutagen in the Ames test. This suggested that plasma led to the generation of both extracellular and intracellular reactive species, particularly nitrogen species, which affect cell proliferation and are also known to induce genetic damage in fibroblast cells. These results highlight the genotoxic and mutagenic effects of ANTP, emphasizing the need for the cautious selection of plasma intensity in specific applications to avoid adverse side effects resulting from reactive species production.

Glioblastoma multiforme, a deadly form of brain tumor, is characterized by aggressive growth and poor prognosis. Oxidative stress, a disruption in the balance between antioxidants and oxidants, is a crucial factor in its pathogenesis. Silymarin, a flavonoid extracted from milk thistle, has shown therapeutic potential in inhibiting cancer cell growth, promoting apoptosis, and reducing inflammation. It also regulates oxidative stress. This study aims to investigate the regulatory effects of silymarin on oxidative stress parameters, especially the transcription factor Nrf2 and its related enzymes in GBM cancer cells, to develop a new anti-cancer compound with low toxicity.

First, the cytotoxicity of silymarin on U-87 MG cells was investigated by MTT and the results showed an IC50 of 264.6 μM. Then, some parameters of the redox system were measured with commercial kits, and the obtained results showed that silymarin increased the activity of catalase and superoxide dismutase enzymes, as well as the total antioxidant capacity levels; while the malondialdehyde level that is an indicator of lipid peroxidation was decreased by this compound. The expression level of Nrf2 and HO-1 and glutaredoxin and thioredoxin enzymes were checked by real-time PCR method, and the expression level increased significantly after treatment.

Our findings suggest that silymarin may exert its cytotoxic and anticancer effects by enhancing the Nrf2/HO-1 pathway through antioxidant mechanisms in U-87 MG cells.

This study emphasizes the importance of considering the metabolic and toxicity mechanisms of environmental concern chemicals in real-life exposure scenarios. Furthermore, environmental chemicals may require metabolic activation to become toxic, and competition for binding sites on receptors can affect the severity of toxicity. The multicomplex process of chemical toxicity is reflected in the activation of multiple pathways during toxicity of which AhR activation is major. Real-life exposure to a mixture of concern chemicals is common, and the composition of these chemicals determines the severity of toxicity. Nutritional essential elements can mitigate the toxicity of toxic heavy metals, while the types and ratio of composition of PAH can either increase or decrease toxicity. The epigenetic mechanisms of heavy metals and PAH toxicity involves either down-regulation or up-regulation of some non-coding RNAs (ncRNAs) whereas specific small RNAs (sRNAs) may have dual role depending on the tissue and circumstance of expression. Similarly, decrease DNA methylation and histone modification are major players in heavy metals and PAH mediated toxicity and FLT1 hypermethylation is a major process in PAH induced carcinogenesis. Overall, this review provides the understanding of the metabolism of environmental concern chemicals, emphasizing the importance of considering mixed compositions and real-life exposure scenarios in assessing their potential effects on human health and diseases development as well as the dual mechanism of toxicity via genetic or epigenetic axis.

Background: With the advancement of medicine and the development of technology, the limiting factors of aeromedical evacuation are gradually decreasing, and the scope of indications is expanding. However, the hypobaric and hypoxic environments experienced by critically ill patients in flight can cause lung injury, leading to inflammation and hypoxemia, which remains one of the few limiting factors for air medical evacuation. This study aimed to examine the mechanism of secondary lung injury in rat models of acute lung injury that simulate aeromedical evacuation. Methods: An acute lung injury model was induced in SD rats by the administration of lipopolysaccharide (LPS) followed by exposure to a simulated aeromedical evacuation environment (equivalent to 8,000 feet above sea level) or a normobaric normoxic environment for 4 h. The expression of hypoxia-inducible factor 1α (HIF-1α) was stabilized by pretreatment with dimethyloxalylglycine. The reactive oxygen species levels and the protein expression levels of HIF-1α, Bcl-2-interacting protein 3 (BNIP3), and NIX in lung tissue were measured. Results: Simulated aeromedical evacuation exacerbated pathological damage to lung tissue and increased the release of inflammatory cytokines in serum as well as the reactive oxygen species levels and the protein levels of HIF-1α, BNIP3, and NIX in lung tissue. Pretreatment with dimethyloxalylglycine resulted in increases in the protein expression of HIF-1α, BNIP3, and NIX. Conclusion: Simulated aeromedical evacuation leads to secondary lung injury through mitophagy.

This review explores the nuanced role of reactive oxygen species (ROS) in cell fate, challenging the traditional view that equates ROS with cellular damage. Through significant technological advancements in detecting localized redox states and identifying oxidized cysteines, a paradigm shift has emerged: from ROS as merely damaging agents to crucial players in redox signaling. We delve into the intricacies of redox mechanisms, which, although confined, exert profound influences on cellular physiological responses. Our analysis extends to both the positive and negative impacts of these mechanisms on cell death processes, including uncontrolled and programmed pathways. By unraveling these complex interactions, we argue against the oversimplified notion of a 'stress response', advocating for a more nuanced understanding of redox signaling. This review underscores the importance of localized redox states in determining cell fate, highlighting the sophistication and subtlety of ROS functions beyond mere damage.

Considering the high frequency of malignant breast tumors, there is a growing search for new therapeutic strategies that control neoplastic growth and dissemination, combined with fewer adverse reactions. Therefore, this study evaluated the effects of ozone therapy in female dogs with mammary cancer undergoing chemotherapy treatment. Twenty-five canines diagnosed with malignant mammary neoplasia were divided into two groups: one treated with carboplatin alone (n = 11) and the other with carboplatin associated with ozone therapy (n = 14). Clinical and laboratory evaluations, mastectomy, analysis of the oxidative profile based on total antioxidant capacity (TAC) and serum concentrations of malondialdehyde (MDA), survival rate, and quality of life were performed. Animals in the ozone therapy group had higher concentrations of red blood cells and platelets, significantly improving the survival rate and quality of life. Furthermore, adverse reactions were less intense and frequent in this group, which was associated with an increase in TAC and a reduction in MDA. These results indicate that the combination of carboplatin and ozone therapy represents a promising complementary treatment for female dogs with mammary cancer, as it was associated with fewer adverse reactions and a better oxidative profile.

The development of BCR::ABL1-targeting tyrosine kinase inhibitors (TKIs) has improved the prognosis of patients with chronic myeloid leukemia (CML). However, resistance to ABL TKIs can develop in CML patients due to BCR::ABL1 point mutations and CML leukemia stem cell (LSC). Aurora kinases are essential kinases for cell division and regulate mitosis, especially the process of chromosomal segregation. Aurora kinase members also promote cancer cell survival and proliferation. This study analyzed whether aurora kinases were regulated in the progression of CML. It also evaluated the efficacy of the ABL TKI asciminib and the aurora kinase inhibitor LY3295668. The expressions of AURKA and AURKB were higher in the CML cells compared with normal cells using a public database (GSE100026). Asciminib or LY3295668 alone inhibited CML cells after 72 h, and cellular cytotoxicity was increased. The combined use of Asciminib and LY3295668 increased superior efficacy compared with either drug alone. Colony formation was reduced by cotreatment with asciminib and LY3295668. In the cell-cycle analyses, LY3295668 induced G2/M arrest. Cell populations in the sub-G1 phase were observed when cotreating with asciminib and LY3295668. The combination treatment also changed the mitochondrial membrane potential. In addition, AURKA shRNA transfectant cells had increased asciminib sensitivity. Combining asciminib and aurora kinase inhibition enhanced the efficacy and is proposed as a new therapeutic option for patients with CML. These findings have clinical implications for a potential novel therapeutic strategy for CML patients.

Indomethacin is one of the most widely used non-steroidal anti-inflammatory drugs. This study aimed to investigate the protective effects of curcumin against indomethacin-induced genotoxicity.

For in vitro studies, human peripheral blood lymphocytes were obtained from a healthy volunteer and treated for 24 h as follows: vehicle control, indomethacin at 100 and 200 μΜ, indomethacin (100 μM and 200 μM) plus curcumin (27 μM). For in vivo experiments, mice received a single i.p dose of curcumin (100 mg/kg) and after 30 min genotoxicity induction was carried out by a single i.p injection of indomethacin at 10, 20, and 40 mg/kg. After 24 h, bone marrow cells were obtained from mice femurs. Genotoxicity was evaluated using a micronucleus assay. Oxidative damage was also inspected both in vitro and in vivo.

In-vitro studies indicated that co-treatment with curcumin caused a significant decrease in the average micronuclei percentage and MDA level, and a significant increase in GSH concentration compared to the groups treated only with indomethacin. In-vivo findings revealed that pretreatment with curcumin induced a significant increase in the average ratio of polychromatic erythrocyte/normochromic erythrocyte, GSH concentration and caused a significant decrease in the average percentage of micronuclei and MDA level, in comparison with the group treated only with indomethacin.

Curcumin attenuated indomethacin-induced genotoxicity both in vitro and in vivo. These effects might be partially exerted by decreasing oxidative stress. Further studies are required to elucidate the exact genoprotective mechanism of curcumin against indomethacin.

The chemistry of pure cerium oxide (CeO2-x) nanoparticles has been widely studied since the 1970s, especially for chemical catalysis. CeO2-x nanoparticles have been included in an important class of industrial metal oxide nanoparticles and have been attributed a range of wide applications, such as ultraviolet absorbers, gas sensors, polishing agents, cosmetics, consumer products, high-tech devices and fuel cell conductors. Despite these early applications in the field of chemistry, the biological effects of CeO2-x nanoparticles were only explored in the 2000s. Since then, CeO2-x nanoparticles have gained a spot in research related to various diseases, especially the ones in which oxidative stress plays a part. Due to an innate oxidation state variation on their surface, CeO2-x nanoparticles have exhibited redox activities in diseases, such as cancer, acting either as an oxidizing agent, or as an antioxidant. In biological models, CeO2-x nanoparticles have been shown to modulate cancer cell viability and, more recently, cell death pathways. However, a deeper understanding on how the chemical structure of CeO2-x nanoparticles (including nanoparticle size, shape, suspension, agglomeration in the medium used, pH of the medium, type of synthesis and crystallite size) influences the cellular effects observed remains to be elucidated. In the present review, the chemistry of CeO2-x nanoparticles and their impact on biological models and modulation of cell signalling, particularly focusing on oxidative and cell death pathways, were investigated. The deeper understanding of the chemical activity of CeO2-x nanoparticles may provide the rationale for further biomedical applications towards disease treatment and drug delivery purposes.

Cancer is still one of the most challenging diseases to treat, making the pursuit for novel molecules with potential anticancer activity an important research topic. Herein, we have performed a comparative investigation into the anticancer activity of analogs of marine coelenterazine and coelenteramine. The former is a well-known bioluminescent substrate, while the latter is a metabolic product of the resulting bioluminescent reaction. While both types of analogs showed anticancer activity toward lung and gastric cancer cell lines, we have obtained data that highlight relevant differences between the activity of these two types of compounds. More specifically, we observed relevant differences in structure-activity relationships between these types of compounds. Also, coelenteramine analogs showed time-dependent activity, while coelenterazine-based compounds usually present time-independent activity. Coelenterazine analogs also appear to be relatively safer toward noncancer cells than coelenteramine analogs. There was also seen a correlation between the activity of the coelenterazine-based compounds and their light-emission properties. Thus, these results further indicate the potential of the marine coelenterazine chemi-/bioluminescent system as a source of new molecules with anticancer activity, while providing more insight into their modes of action.