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Purpose: Heparan sulfate proteoglycans (HSPGs) are complex molecules found on the cell membrane and within the extracellular matrix, increasingly recognized for their role in tumor progression. This study aimed to investigate the involvement of Heparan sulfate proteoglycan 2 (HSPG2) in the progression of bladder cancer. Methods: We identified HSPG2 as a promoter of bladder tumor progression using single-cell RNA sequencing and transcriptome analysis of sequencing data from seven patient samples obtained from the Gene Expression Omnibus (GEO) database (GSE135337). Transcript profiles of 28 normal tissues and 407 bladder tumor tissues were analyzed for HSPG2 expression and survival outcomes using the Sanger tools and cBioPortal databases. HSPG2-overexpressing T24 and Biu-87 cell lines were generated, and cell proliferation and migration were assessed using CCK-8 and Transwell assays. Western blotting and immunostaining were performed to evaluate the activation of Nidogen-1 (NID1)/protein kinase B (AKT) signaling. Mouse models with patient-derived tumor organoids (HSPG2high and HSPG2low) were established to assess anticancer effects. Results: Our results demonstrated a marked upregulation of HSPG2 in malignant bladder tumors, which correlated significantly with poor patient prognosis. HSPG2 overexpression consistently enhanced bladder tumor cell proliferation and conferred chemotherapy resistance, as shown in both in vitro and in vivo experiments. Mechanistically, HSPG2 upregulated NID1 expression, leading to the activation of the AKT pro-survival signaling pathway and promoting sustained tumor growth in bladder cancer. Conclusion: This study highlights the critical pro-tumor role of HSPG2/NID1/AKT signaling in bladder cancer and suggests its potential as a therapeutic target in clinical treatment. [ABSTRACT FROM AUTHOR]

AbstractIn recent years, there has been a growing focus on the issue of exposure to hazardous chemical compounds and the potential health risks associated with them. Fuel stations play a critical role in society, supporting the transportation industry and serving the general public. However, the routine activities at these stations expose workers and customers to dangerous chemical compounds, posing potential health risks. As part of a pilot study, the exposure of workers and customers to hazardous chemical compounds at fuel stations in Kuwait, characterized by its hot and arid environment, was investigated. The study specifically looked at volatile organic compounds (VOC) concentration and their effects on human health. Three hundred-eight air samples were collected in a hot, arid environment, focusing on fuel stations. Two sampling methods were used in this pilot study: personal inhalation exposure using active sampling and workplace air sampling using passive sampling. Samples were collected in fuel filling areas, indoor control rooms, and through personal exposures, adhering to ISO procedures (EPA TO-17). The study also assessed the non-carcinogenic and carcinogenic risks to human health to potential exposure to hazardous hazardous chemicals. The findings revealed that hazardous chemicals levels in the pump area were lower than those in the indoor control rooms. Workers’ inhalation exposure to hazardous chemicals remained below the international occupational exposure limit (OEL). However, the study identified unsafe inhalation exposure levels to Benzene, which could have adverse carcinogenic effects. In contrast, exposure to ethylbenzene was found to be within safe limits, with no associated carcinogenic effects. This study underscores the importance of identifying the risks associated with exposure to hazardous chemical compounds to minimize human health risks and promote a safe working environment. [ABSTRACT FROM AUTHOR]

Nitrosamine compounds pose a significant concern as potential carcinogens, prompting heightened scrutiny from regulatory bodies, particularly regarding their presence in pharmaceuticals. The detection of unacceptable levels of N‐nitrosodiethylamine (NDMA) in ranitidine has led to widespread recalls, driving interest in alternative medications such as nizatidine, which shares a similar pharmacological class and is used to treat various gastrointestinal conditions. Despite fewer reports on NDMA levels in nizatidine, its structural similarity to ranitidine, characterized by a tertiary amine, underscores the potential for NDMA formation. Addressing the analytical challenges associated with nitrosamine detection, this study focuses on developing and validating an ultra‐high pressure liquid chromatography triple quadrupole mass spectrometry (UHPLC–MS/MS) method for quantifying NDMA in both nizatidine active pharmaceutical ingredients and tablet formulations. Method validation adheres to International Council for Harmonisation recommendations, with a demonstrated linear range of 0.25–100 ng/mL for NDMA, exhibiting excellent linearity (regression coefficient >0.999) and efficient recovery rates ranging from 95.98% to 109.57%. The method shows high sensitivity, with limits of detection and quantification of 0.25 and 0.5 ng/mL, respectively. The developed UHPLC–MS/MS method offers a simple, precise, accurate, and selective approach for monitoring NDMA levels in nizatidine formulations available in Australia, promising enhanced sensitivity and specificity with limits of quantification in the ppb and sub‐ppb ranges. [ABSTRACT FROM AUTHOR]

Prostate cancer, the most common malignancy in men, has a relatively favourable prognosis. However, when it spreads to the bone, the survival rate drops dramatically. The development of bone metastases leaves patients with aggressive prostate cancer, the leading cause of death in men. Moreover, bone metastases are incurable and very painful. Hepatocyte growth factor receptor (MET) and fusion of genes encoding E26 transformation‐specific (ETS) transcription factors are both involved in the progression of the disease. ETS gene fusions, in particular, have the ability to induce the migratory and invasive properties of prostate cancer cells, whereas MET receptor, through its signalling cascades, is able to activate transcription factor expression. MET signalling and ETS gene fusions are intimately linked to high‐grade prostate cancer. However, the collaboration of these factors in prostate cancer progression has not yet been investigated. Here, we show, using cell models of advanced prostate cancer, that ETS translocation variant 1 (ETV1) and transcriptional regulator ERG (ERG) transcription factors (members of the ETS family) promote tumour properties, and that activation of MET signalling enhances these effects. By using a specific MET tyrosine kinase inhibitor in a humanised hepatocyte growth factor (HGF) mouse model, we also establish that MET activity is required for ETV1/ERG‐mediated tumour growth. Finally, by performing a comparative transcriptomic analysis, we identify target genes that could play a relevant role in these cellular processes. Thus, our results demonstrate for the first time in prostate cancer models a functional interaction between ETS transcription factors (ETV1 and ERG) and MET signalling that confers more aggressive properties and highlight a molecular signature characteristic of this combined action. [ABSTRACT FROM AUTHOR]

Many nations have food contact material (FCM) legislation purporting to protect citizens from hazardous chemicals, often specifically by regulating genotoxic carcinogens. Despite such regulations, cancers that are associated with harmful chemical exposures are highly prevalent, especially breast cancer. Using the novel Key Characteristics of Toxicants framework, Kay et al. found 921 substances that are potential mammary carcinogens. By comparing Kay et al.'s chemicals list with our own Database on migrating and extractable food contact chemicals (FCCmigex), we found that 189 (21%) of the potential mammary carcinogens have been measured in FCMs. When limiting these results to migration studies published in 2020-2022, 76 potential mammary carcinogens have been detected to migrate from FCMs sold in markets across the globe, under realistic conditions of use. This implies that chronic exposure of the entire population to potential mammary carcinogens from FCMs is the norm and highlights an important, but currently underappreciated opportunity for prevention. Reducing population-wide exposure to potential mammary carcinogens can be achieved by science-based policy amendments addressing the assessment and management of food contact chemicals. [ABSTRACT FROM AUTHOR]

This article explores the role of LRPPRC in pancreatic cancer progression. The study found that LRPPRC is upregulated in pancreatic cancer tissues and cell lines and is negatively associated with overall survival rate. Knockdown of LRPPRC led to increased reactive oxidative species accumulation, decreased mitochondrial membrane potential, and induced autophagy/mitophagy and mitochondrial dysfunction. The study suggests that LRPPRC may act as an oncogene by maintaining mitochondrial homeostasis and could be used as a predictive marker for patient prognosis in pancreatic cancer. [Extracted from the article]

The tumor microenvironment (TME) is a critical determinant in the initiation, progression, and treatment outcomes of various cancers. Comprising of cancer‐associated fibroblasts (CAF), immune cells, blood vessels, and signaling molecules, the TME is often likened to the soil supporting the seed (tumor). Among its constituents, tumor‐associated macrophages (TAMs) play a pivotal role, exhibiting a dual nature as both promoters and inhibitors of tumor growth. This review explores the intricate relationship between TAMs and the TME, emphasizing their diverse functions, from phagocytosis and tissue repair to modulating immune responses. The plasticity of TAMs is highlighted, showcasing their ability to adopt either protumorigenic or anti‐tumorigenic phenotypes based on environmental cues. In the context of cancer, TAMs' pro‐tumorigenic activities include promoting angiogenesis, inhibiting immune responses, and fostering metastasis. The manuscript delves into therapeutic strategies targeting TAMs, emphasizing the challenges faced in depleting or inhibiting TAMs due to their multifaceted roles. The focus shifts towards reprogramming TAMs to an anti‐tumorigenic M1‐like phenotype, exploring interventions such as interferons, immune checkpoint inhibitors, and small molecule modulators. Noteworthy advancements include the use of CSF1R inhibitors, CD40 agonists, and CD47 blockade, demonstrating promising results in preclinical and clinical settings. A significant section is dedicated to Chimeric Antigen Receptor (CAR) technology in macrophages (CAR‐M cells). While CAR‐T cells have shown success in hematological malignancies, their efficacy in solid tumors has been limited. CAR‐M cells, engineered to infiltrate solid tumors, are presented as a potential breakthrough, with a focus on their development, challenges, and promising outcomes. The manuscript concludes with the exploration of third‐generation CAR‐M technology, offering insight into in‐vivo reprogramming and nonviral vector approaches. In conclusion, understanding the complex and dynamic role of TAMs in cancer is crucial for developing effective therapeutic strategies. While early‐stage TAM‐targeted therapies show promise, further extensive research and larger clinical trials are warranted to optimize their targeting and improve overall cancer treatment outcomes. Highlights: Tumor microenvironment (TME) is a critical determinant of tumor behavior.Tumor‐associated macrophages (TAM) plays a crucial role in the TME.TAMs are a diverse population of immune cells that can exhibit different phenotypes or functions.TAMs can switch between different activation states or phenotypes.Numerous preclinical and clinical studies have revealed that targeting TAMs can be an effective approach towards tumor treatment. [ABSTRACT FROM AUTHOR]

Background: Spitz tumors are relatively uncommon melanocytic lesions, typically affecting a relatively younger population but can be encountered at any age. They are characterized by a proliferation of melanocytes with epithelioid and/or spindled cytomorphology features, and interpretation is often challenging. The majority of these tumors are driven by kinase fusions or HRAS mutations. MAP3K8 fusions, although rare, are characteristic genomic events in Spitz tumors, especially in more atypical or malignant lesions. Case presentation: Here, we present the case of a 43-year-old woman with a clinically cystic mass in her right groin, histologically characterized as a spindle and epithelioid cell malignant tumor. Immunohistochemistry revealed diffuse expression of S100 protein, tyrosinase and SOX10, patchy weak PRAME, HMB45 and Melan-A reactivity, and negative staining for BRAF V600E. Next-generation sequencing analysis revealed the presence of a MAP3K8::ABLIM1 fusion gene, as well as GRIN2A and TERT promoter mutations. The morphology, immunohistochemistry and molecular analysis confirmed Spitz melanoma with molecular features suggesting a worse prognosis. Conclusion: This case introduces a novel fusion partner of MAP3K8 in the context of Spitz melanoma and expands the morphologic and molecular spectrum of Spitz melanoma. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyse the attributable risk of mortality and DALYs (Disability Adjusted Life Years) due to occupational carcinogens for lung cancer between 1990 and 2019 in Brazil and federation units, as well as its relationship with the Socio-demographic Index (SDI). Epidemiological study. This is an epidemiological study that used GBD 2019 (Global Burden of Disease Study) estimates of lung cancer mortality rates and DALYs attributable to occupational carcinogens. The relationship between these rates and SDI was assessed using panel data analysis. In Brazil, occupational exposure to asbestos, silica and diesel vapours accounted for more than 85.00% of lung cancer deaths and DALYs attributable to occupational carcinogens in both sexes between 1990 and 2019. An increase in both rates was observed in women for almost all the occupational carcinogens assessed, especially in the North and Northeast regions of the country, with diesel vapours standing out the most. The present study highlighted the urge to characterise exposure to occupational risks for lung cancer, especially for the female population in the North and Northeast regions of Brazil. [ABSTRACT FROM AUTHOR]

Recent advancements in single‐molecule methods have not only made it possible to obtain precise measurements for complex biological processes but also to produce simple mathematical models for intricate biochemical mechanisms, which would otherwise be speculative. These developments have strengthened our ability to respond through mathematical modeling to concepts of protein‒protein and protein‒DNA interactions on a nanometer level and address‐related questions. In this article, we examine an intriguing biological phenomenon in which a protein and an enzyme co‐jointly encounter carcinogenic adducts during transcription. We are focusing mainly on the dysregulation of the protein involved and the possible consequences that may arise. By providing a quantum mechanical model, we have demonstrated that the presence of carcinogenic adducts in a transcriptional bubble deregulates the protein that could cause lethal mutations. Next, we present a case study to explore carcinogenesis by suggesting an alternative experimental design. Our quantum mechanical model emphasizes the use of a quantized energies approach for specific mechanisms within the living cells. Radiation‐induced carcinogenicity can be prevented if radiation interacting with tissue is not given the energies that satisfy the quantization conditions. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs), carcinogenic substances primarily formed through pyrolysis and oxidation of fat at high cooking temperatures, are commonly found at high levels in grilled meats. Reducing PAHs formation by incorporating natural antioxidants, such as through marination, has been demonstrated to be effective. However, the inhibitory effect of fresh phenolic-rich fruit powders on PAHs formation in charcoal-grilled meats remains unknown. To clarify the application of the fruit powders, 15 experimental groups were conducted. All pretreatment techniques (spraying, marinating, and mixing) were applied across all four freeze-dried fruit powders (lemon, guava, papaya, and mango). Each method was systematically tested with each fruit powder to evaluate its effect on inhibiting the formation of the four PAHs (BaA, CHR, BbF, and BaP) in charcoal-grilled pork belly and loin. Firstly, guava powder exhibited the highest phenolic content and antioxidant activity compared to the lemon, papaya, and mango powders (p < 0.05), among which the main phenolic compounds were ellagic acid, quercetin, and epigallocatechin gallate (EGCG). Further, marination of pork belly with guava powder exhibited the highest inhibition rate of PAHs (94.8%), followed by lemon (91.1%), papaya (89.8%), and mango (89.0%), with a statistically significant difference at p < 0.05. The reduction in estimated daily intake (EDI) and the increase in the margin of exposure (MOE) indicate that consuming grilled meat treated with these fruit powders poses no safety concerns and may potentially reduce health risks. Finally, the sensory evaluation showed that marinating with guava powder did not perceptibly affect the sensory attributes of the meat. Overall, this study provides a potent strategy for inhibiting the formation of PAHs in meat during charcoal grilling by incorporating fruit powder while preserving sensory qualities. [ABSTRACT FROM AUTHOR]

SMYD3 (SET and MYND domain‐containing 3) is a histone lysine methyltransferase highly expressed in different types of cancer(s) and is a promising epigenetic target for developing novel antitumor therapeutics. No selective inhibitors for this protein have been developed for cancer treatment. Therefore, the current study describes developing and characterizing a novel small molecule ZYZ384 screened and synthesized based on SMYD3 structure. Virtual screening was initially used to identify a lead compound and followed up by modification to get the novel molecules. Several technologies were used to facilitate compound screening about these novel molecules' binding affinities and inhibition activities with SMYD3 protein; the antitumor activity has been assessed in vitro using various cancer cell lines. In addition, a tumor‐bearing nude mice model was established, and the activity of the selected molecule was determined in vivo. Both RNA‐seq and chip‐seq were performed to explore the antitumor mechanism. This work identified a novel small molecule ZYZ384 targeting SMYD3 with antitumor activity and impaired hepatocellular carcinoma tumor growth by reducing H3K4 trimethylation of the Rac1 promoter triggering the tumor cell cycle arrest through the AKT pathway. [ABSTRACT FROM AUTHOR]

Purpose: Cancer registries offer an avenue to identify cancer clusters across large populations and efficiently examine potential environmental harms affecting cancer. The role of known metal carcinogens (i.e., cadmium, arsenic, nickel, chromium(VI)) in breast and colorectal carcinogenesis is largely unknown. Historically marginalized communities are disproportionately exposed to metals, which could explain cancer disparities. We examined area-based metal exposures and odds of residing in breast and colorectal cancer hotspots utilizing state tumor registry data and described the characteristics of those living in heavy metal-associated cancer hotspots. Methods: Breast and colorectal cancer hotspots were mapped across Kentucky, and area-based ambient metal exposure to cadmium, arsenic, nickel, and chromium(VI) were extracted from the 2014 National Air Toxics Assessment for Kentucky census tracts. Among colorectal cancer (n = 56,598) and female breast cancer (n = 77,637) diagnoses in Kentucky, we used logistic regression models to estimate Odds Ratios (ORs) and 95% Confidence Intervals to examine the association between ambient metal concentrations and odds of residing in cancer hotspots, independent of individual-level and neighborhood risk factors. Results: Higher ambient metal exposures were associated with higher odds of residing in breast and colorectal cancer hotspots. Populations in breast and colorectal cancer hotspots were disproportionately Black and had markers of lower socioeconomic status. Furthermore, adjusting for age, race, tobacco and neighborhood factors did not significantly change cancer hotspot ORs for ambient metal exposures analyzed. Conclusion: Ambient metal exposures contribute to higher cancer rates in certain geographic areas that are largely composed of marginalized populations. Individual-level assessments of metal exposures and cancer disparities are needed. [ABSTRACT FROM AUTHOR]

Crude palm oil (CPO) is the most produced vegetable oil globally, with Brazil contributing only 0.74% of global production. Pará and Bahia account for more than 82% of Brazil's output. Despite its widespread use in the food industry after refining, there is little research on CPO consumption and perception in Brazil, particularly regarding its nutritional aspects. This study, conducted between March and July 2022, explored Brazilians' perceptions and the potential for CPO consumption. The results show that most participants are unfamiliar with CPO but view its nutrients favorably. Less than half regularly purchase CPO. Refined palm oil (RPO) is even less known, with many unaware that refining CPO can produce carcinogenic substances. The respondents showed little concern about RPO in their foods, rarely noticing its presence on labels. Despite limited knowledge, participants understand that refining reduces CPO's health benefits, leading to a greater preference for crude oil over refined oil. This study highlights the need for better dissemination of information about CPO in Brazil, emphasizing its nutritional benefits and the importance of adhering to daily lipid intake limits. Adding CPO at the end of cooking or consuming it raw to preserve thermosensitive compounds is also recommended. [ABSTRACT FROM AUTHOR]

Triple Negative Breast Cancer (TNBC) is a highly aggressive and treatment-resistant subtype of breast cancer, lacking the expression of estrogen, progesterone, and HER2 receptors. Conventional chemotherapy remains the primary treatment option, but its efficacy is often compromised by the development of drug resistance. Nanoquercetin has garnered the attention of researchers due to its potential in combating cancer. This antioxidant exhibits significant efficacy against various types of cancer, including blood, breast, pancreatic, prostate, colon, and oral cancers. Functioning as a potential anti-cancer agent, nanoquercetin impedes the development and proliferation of cancer cells, induces apoptosis and autophagy, and prevents cancer cell invasion and metastasis. Numerous processes, such as the inhibition of pathways linked to angiogenesis, inflammation, and cell survival, are responsible for these anticancer actions. Moreover, it shields DNA from degradation caused by radiation and other carcinogens. The cost-effectiveness of current cancer treatments remains a significant challenge in healthcare, imposing a substantial economic burden on societies worldwide. Preclinical studies and early-phase clinical trials indicate that nanoquercetin-based therapies could offer a significant advancement in the management of TNBC, providing a foundation for future research and clinical application in overcoming drug resistance and improving patient outcomes. This article examines the latest data on nanoquercetin's potent anti-cancer properties and interprets the accumulated research findings within the framework of preventive, predictive, and personalized (3P) medicine. [ABSTRACT FROM AUTHOR]

Pancreatic cancer continues to be a deadly disease because of its delayed diagnosis and aggressive tumor biology. Oncogenes and risk factors are being reported to influence the signaling pathways involved in pancreatic embryogenesis leading to pancreatic cancer genesis. Although studies using rodent models have yielded insightful information, the scarcity of human pancreatic tissue has made it difficult to comprehend how the human pancreas develops. Transcription factors like IPF1/PDX1, HLXB9, PBX1, MEIS, Islet-1, and signaling pathways, including Hedgehog, TGF-β, and Notch, are directing pancreatic organogenesis. Any derangements in the above pathways may lead to pancreatic cancer. TP53: and CDKN2A are tumor suppressor genes, and the mutations in TP53 and somatic loss of CDKN2A are the drivers of pancreatic cancer. This review clarifies the complex signaling mechanism involved in pancreatic cancer, the same signaling pathways in pancreas development, the current therapeutic approach targeting signaling molecules, and the mechanism of action of risk factors in promoting pancreatic cancer. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) are a small group of cells found in tumors that have same self-renewing properties as nor‑ mal stem cells. In recent years, with continuous development of science and technology in various aspects, people's research on tumor diseases has been deepened. CSCs has been defined as a key factor in promoting tumor development, especially participating in pro‑ moting tumor recurrence, metastasis, chemotherapy resistance, etc. Currently, CD133 has become one of popular CSCs markers, and can be highly expressed in a variety of CSCs. CD133 is closely related to diagnosis of cancer diseases, and plays an important role in dignosis and drug targeting for gastric cancer, lung cancer, brain tumor, liver cancer, ovarian cancer and colorectal cancer. This article reviews structure, function, immune mechanism escape of CD133, signal pathway of CD133 in tumorigenesis, and correlation of CD133 with various tumors as well. [ABSTRACT FROM AUTHOR]

The protein menin is encoded by the MEN1 gene and primarily serves as a nuclear scaffold protein, regulating gene expression through its interaction with and regulation of chromatin modifiers and transcription factors. While the scope of menin's functions continues to expand, one area of growing investigation is the role of menin in cancer. Menin is increasingly recognized for its dual function as either a tumor suppressor or a tumor promoter in a highly tumor-dependent and context-specific manner. While menin serves as a suppressor of neuroendocrine tumor growth, as seen in the cancer risk syndrome multiple endocrine neoplasia type 1 (MEN1) syndrome caused by pathogenic germline variants in MEN1, recent data demonstrate that menin also suppresses cholangiocarcinoma, pancreatic ductal adenocarcinoma, gastric adenocarcinoma, lung adenocarcinoma, and melanoma. On the other hand, menin can also serve as a tumor promoter in leukemia, colorectal cancer, ovarian and endometrial cancers, Ewing sarcoma, and gliomas. Moreover, menin can either suppress or promote tumorigenesis in the breast and prostate depending on hormone receptor status and may also have mixed roles in hepatocellular carcinoma. Here, we review the rapidly expanding literature on the role and function of menin across a broad array of different cancer types, outlining tumor-specific differences in menin's function and mechanism of action, as well as identifying its therapeutic potential and highlighting areas for future investigation. [ABSTRACT FROM AUTHOR]

Background 1,4-Dioxane (1,4-D) is a byproduct of the synthesis of surfactants, typically found in some cosmetics products such as shampoo, toothpaste, and soap. The presence of 1,4-D in cosmetics products is limited to a certain amount since 1,4-D is classified as a probable human carcinogen. Objective This present study was intended to validate static headspace gas chromatography-mass spectrometry (HS GC-MS) for the determination of 1,4-D in cosmetics products. Methods The condition of HS and GC-MS was optimized to get the best condition for analysis of 1,4-D using 1,4-dioxane-d8 (1,4-D-d8) as internal standard (IS). The developed method was validated by evaluating the key performance characteristics, including specificity, linearity, limit of detection (LoD), limit of quantification (LoQ), accuracy, and precision. Results The results showed that HS GC-MS was specific since the peaks of the selected ion monitoring (SIM) mode could be separated and confirmed at m/z 88 and m/z 96 for 1,4-D and 1,4-D-d8, respectively. The method was linear over the concentration range of 0.1287–1.2875 µg/mL, with R2 > 0.999 and RSD residuals <2.0. A collaborative study was conducted on this method, with 10 participating laboratories from four countries. The outcome of this study was found to be accurate and precise, as evidenced by the excellent recoveries ranging from 94.6% to 102.1%, and with good reproducibility with RSD values ranging from 0.2 to 1.1%. The collaborative studies exhibited that all data reported by 10 participating laboratories in four countries were inliers without any extreme values observed either in mean or RSD values Conclusions HS GC-MS is found to be fit and suitable for the determination of trace level of 1,4-D in cosmetics products. Highlights The HS GC-MS method could be proposed as a standard method for quantitative analysis of 1,4-D in cosmetics products since the collaborative studies indicated that the developed method meet the requirement in "Guidelines for Collaborative Study Procedures to Validate Characteristics of a Method of Analysis." [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer cells exhibit several key characteristics, including uncontrolled growth, altered metabolism, enhanced survival mechanisms, and resistance to apoptosis, all of which are crucial for their persistence. In our study, we explored the impact of disrupting the production of mitochondrial gatekeeper protein VDAC1 on lung cancer. We induced lung cancer in mice using the chemical urethane, which closely mimics human lung cancer in terms of genetic mutations and molecular changes. Using MRI to monitor the lung tumors, we found that inhibiting VDAC1 expression in this mouse model led to significant changes: reprogramming of cancer cell metabolism, reduced tumor growth, alterations in the tumor microenvironment, and elimination of cancer stem cells (CSCs). Additionally, treatment with a peptide derived from VDAC1 also inhibited tumor growth and decreased CSC markers. These findings suggest that targeting VDAC1, either through depletion or with a cell-penetrating peptide, could be a promising therapeutic approach for lung cancer. Alterations in cellular metabolism are vital for cancer cell growth and motility. Here, we focused on metabolic reprogramming and changes in tumor hallmarks in lung cancer by silencing the expression of the mitochondrial gatekeeper VDAC1. To better mimic the clinical situation of lung cancer, we induced lung cancer in A/J mice using the carcinogen urethane and examined the effectiveness of si-m/hVDAC1-B encapsulated in PLGA-PEI nanoparticles. si-m/hVDAC1-B, given intravenously, induced metabolism reprogramming and inhibited tumor growth as monitored using MRI. Mice treated with non-targeted (NT) PLGA-PEI-si-NT showed many large size tumors in the lungs, while in PLGA-PEI-si-m/hVDAC-B-treated mice, lung tumor number and area were markedly decreased. Immunofluorescence staining showed decreased expression of VDAC1 and metabolism-related proteins and altered expression of cancer stem cell markers. Morphological analysis showed two types of tumors differing in their morphology; cell size and organization within the tumor. Based on specific markers, the two tumor types were identified as small cell (SCLC) and non-small cell (NSCLC) lung cancer. These two types of tumors were found only in control tumors, suggesting that PLGA-PEI-si-m/hVDAC1-B also targeted SCLC. Indeed, using a xenograft mouse model of human-derived SCLC H69 cells, si-m/hVDAC1-B inhibited tumor growth and reduced the expression of VDAC1 and energy- and metabolism-related enzymes, and of cancer stem cells in the established xenograft. Additionally, intravenous treatment of urethane-induced lung cancer mice with the VDAC1-based peptide, Retro-Tf-D-LP4, showed inhibition of tumor growth, and decreased expression levels of metabolism- and cancer stem cells-related proteins. Thus, silencing VDAC1 targeting both NSCLC and SCLC points to si-VDAC1 as a possible therapeutic tool to treat these lung cancer types. This is important as target NSCLC tumors undergo transformation to SCLC. [ABSTRACT FROM AUTHOR]

Superoxide dismutase (SOD) is a crucial enzyme responsible for the redox homeostasis inside the cell. As a part of the antioxidant defense system, it plays a pivotal role in the dismutation of the superoxide radicals (O2−) generated mainly by the oxidative phosphorylation, which would otherwise bring out the redox dysregulation, leading to higher reactive oxygen species (ROS) generation and, ultimately, cell transformation, and malignancy. Several studies have shown the involvement of ROS in a wide range of human cancers. As SOD is the key enzyme in regulating ROS, any change, such as a transcriptional change, epigenetic remodeling, functional alteration, and so forth, either activates the proto‐oncogenes or aberrant signaling cascades, which results in cancer. Interestingly, in some cases, SODs act as tumor promoters instead of suppressors. Furthermore, SODs have also been known to switch their role during tumor progression. In this review, we have tried to give a comprehensive account of SODs multifactorial role in various human cancers so that SODs‐based therapeutic strategies could be made to thwart cancers. [ABSTRACT FROM AUTHOR]

Cancer is a pernicious and pressing medical problem; moreover, it is a failure of multicellular morphogenesis that sheds much light on evolutionary developmental biology. Numerous classes of pharmacological agents have been considered as cancer therapeutics and evaluated as potential carcinogenic agents; however, these are spread throughout the primary literature. Here, we briefly review recent work on ion channel drugs as promising anti-cancer treatments and present a systematic review of the known cancer-relevant effects of 109 drugs targeting ion channels. The roles of ion channels in cancer are consistent with the importance of bioelectrical parameters in cell regulation and with the functions of bioelectric signaling in morphogenetic signals that act as cancer suppressors. We find that compounds that are well-known for having targets in the nervous system, such as voltage-gated ion channels, ligand-gated ion channels, proton pumps, and gap junctions are especially relevant to cancer. Our review suggests further opportunities for the repurposing of numerous promising candidates in the field of cancer electroceuticals. [ABSTRACT FROM AUTHOR]

This study examined the heavy metal content in dust storm samples from Erbil, Iraq, along with four other locations. Using ICP-MS, Cd, Ni, Cr, Hg, Pb, Zn, Mn, Cu, Co, Fe and As were determined. The health risks due to exposure to these metals through ingestion, inhalation and dermal contact were assessed for both adults and children. Non-carcinogenic risks were evaluated using the hazard quotient (HQ) and hazard index (HI). Children faced a cumulative risk with HQ > 0.2 for As and Cr and HI > 1. The carcinogenic risk was measured using the carcinogenic risk factor (CRF), which fell below 10–6, indicating low cancer risk. However, children had a higher cancer risk (10−4 to 10−6) for As. The pollution indices revealed varying pollution levels from unpolluted to moderately polluted in the studied areas. Overall, this study highlights potential health risks associated with heavy metal exposure during dust storms, particularly for children, and emphasises the importance of addressing these concerns to safeguard public health. [ABSTRACT FROM AUTHOR]

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Background Lead (Pb) content in lipsticks and potential life-long exposure of which might cause severe effects in consumers are an important concern for public. Thus, studies emphasize that lead exposure has no safe levels. Methods From 10 different brands, in total, 25 solid, gloss and creamy lipsticks are deployed from Turkish markets that are also categorized in two different price ranges. In order to evaluate the blood Pb levels in children, the United States Environmental Protection Agency's 'Exposure Uptake Biokinetic Model' is utilized. To assess the health risk of chronic usage both for children and adults, oral daily systemic exposure levels are calculated with the worst-case scenario and are compared with Maximum Allowable Dose Level for lipsticks. For lifetime risk assessment, exposure is assumed to start by age 7, and four different exposure scenarios have been deployed. Results The mean lead content of lipsticks shows significant statistical differences between the high- and low-priced lipstick groups. Daily level and total risk for lifetime Pb exposure from deployed lipsticks are below the acceptable risk levels but long-worn usage of products with routine monitoring of metal content is crucial for sensitive and unintended exposure groups. [ABSTRACT FROM AUTHOR]

Fried potato products are the largest dietary source of acrylamide, a potential carcinogen formed at high temperatures. Previous studies suggested that garlic powder could decrease the development of acrylamide; however, there has not been much focus on the effect of garlic extract. The aim of this study was to investigate the effect of garlic extract exposure on the development of acrylamide in French fries in popular home cooking techniques such as pan-frying, air-frying, and oven-frying. Initially, the antioxidative profile, total phenolic content, and chlorogenic acid content of garlic were analyzed. Subsequently, potatoes were treated with garlic extract and fried using pan-frying, air-frying, and oven-frying techniques. Acrylamide levels were then quantified through HPLC and compared to control groups. The findings showed that garlic exposure increased the acrylamide formation in French fries obtained with air-frying (311.95 ± 0.5 μg/kg) and with oven-frying (270.32 ± 23.4 μg/kg) (p < 0.005 *). This study offers new insights into varying acrylamide formation levels in domestic practices. Unlike previous studies, this study is the first to question the effect of aqueous garlic extract exposure. Further research is required to comprehend the interaction between garlic exposure and acrylamide formation in household settings. [ABSTRACT FROM AUTHOR]

In this study, a novel quantum mechanics-based protocol for the evaluation of carcinogen-scavenging activity (QM-CSA) is developed. The QM-CSA protocol represents a universal and quantitative approach to evaluate and compare the activation-free energies for alkylation reactions between individual polyphenolic compounds and chemical carcinogens of the epoxy type at physiological conditions by applying two scales: the absolute scale allowing for the comparison with guanine and the relative scale allowing the comparison with glutathione as a reference compound. The devised quantum mechanical methodology was validated by comparing the activation-free energies calculated with 14 DFT functionals in conjunction with two implicit solvation models (SMD and CPCM) and the experimental activation-free energies for reactions between nine investigated chemical carcinogens and guanine. According to the obtained results, the best agreement with experimental data was achieved by applying DFT functionals M11-L and MN12-L in conjunction with the flexible 6-311++G(d,p) basis set and implicit solvation model SMD, and the obtained uncertainties were proven to be similar to the experimental ones. To demonstrate the applicability of the QM-CSA protocol, functionals M11-L, and MN12-L in conjunction with the SMD implicit solvation model were applied to calculate activation-free energies for the reactions of nine investigated chemical carcinogens of the epoxy type with three catechins, namely EGCG, EGC, and (+)-catechin. The order of CSA in this series of catechins in comparison to guanine and glutathione was determined as (+)-catechin > EGC > EGCG. The obtained results, for the first time, demonstrated the evaluation and comparison of CSA in a series of selected catechins with respect to glutathione and guanine. Moreover, the presented results provide valuable insights into the reaction mechanisms and configurations of the corresponding transition states. The novel QM-CSA protocol is also expected to expand the kinetic data for alkylation reactions between various polyphenolic compounds and chemical carcinogens of the epoxy type, which is currently lacking in the scientific literature. [ABSTRACT FROM AUTHOR]

Aspartame, invented in 1965 by GD-Searle, is an intense artificial sweetener taste approximately 200 times as sweet as sucrose and used as an additive in more than 6,000 products. Aspartame (APM) was submitted for pre-marketing safety evaluation in early 1980. The studies, performed by GD-Searle, produced controversial results. Because of the great commercial diffusion of aspartame, in 1997 the Ramazzini Institute (RI) started a large experimental project on rodents to test the carcinogenic effects of aspartame following an experimental model with more sensitive characteristics, namely a large number of rat and mice, starting treatment from prenatal life, observation until spontaneous death. Overall, the project included studying 2270 rats and 852 mice. These studies have shown that aspartame is a carcinogenic agent in experimental animals, inducing a significant dose-related increased incidence of several types of malignant tumors and, among them, hematological neoplasia, and liver cancer. The results of these studies on aspartame by the Ramazzini Institute opened a real front on the evaluation of artificial sweeteners and their possible health risks. Adequate long-term carcinogenicity bioassays on other diffuse artificial sweeteners such as acesulfame-k, sucralose, saccharin, including their blends, are likewise important for public health. [ABSTRACT FROM AUTHOR]

Most breast cancer deaths are caused by malignant estrogen receptor–positive breast tumors that later recur as metastatic disease. Prolactin (PRL) has been documented as a factor promoting breast cancer development and metastasis. We therefore developed superactive prolactin receptor (PRLR) antagonists aimed at blocking PRL action. We purified 12 novel mutants to homogeneity as monomers, and the most potent antagonist was over 95-fold more active than the previously reported weak antagonist, the mutant Del 1-9 human PRL G129R. This enhanced antagonistic activity resulted mostly from prolonged interaction with the extracellular domain (ECD) of PRLR. All mutants were properly refolded, as indicated by interaction with human PRLR-ECD and by circular dichroism analysis. We then prepared monopegylated variants of the most active mutants to extend their biological half-life in vivo. [ABSTRACT FROM AUTHOR]

Gastrointestinal cancer is the most common malignancy in humans, often accompanied by poor prognosis. N6-methyladenosine (m6A) modification is widely present in eukaryotic cells as the most abundant RNA modification. It plays a crucial role in RNA splicing and processing, nuclear export, translation, and stability. Human AlkB homolog 5 (ALKBH5) is a type of RNA demethylase exhibiting abnormal expression in various gastrointestinal cancers.It is closely related to the tumorigenesis, proliferation, migration, and other biological functions of gastrointestinal cancer. However, recent studies indicated that the role and mechanism of ALKBH5 in gastrointestinal cancer are complicated and even controversial. Thus, this review summarizes recent advances in elucidating the role of ALKBH5 as a tumor suppressor or promoter in gastrointestinal cancer. It examines the biological functions of ALKBH5 and its potential as a therapeutic target, providing new perspectives and insights for gastrointestinal cancer research. [ABSTRACT FROM AUTHOR]

Adipocyte-cancer cell interactions promote tumor development and progression. Previously, we identified adipsin (CFD) and its downstream effector, hepatocyte growth factor (HGF), as adipokines that enhance adipocyte-breast cancer stem cell interactions. Here, we show that adipsin-dependent adipocyte maturation and the subsequent upregulation of HGF promote tumor invasion in breast cancers. Mature adipocytes, but not their precursors, significantly induced breast tumor cell migration and invasion in an adipsin expression-dependent manner. Promoters of tumor invasion, galectin 7 and matrix metalloproteinases, were significantly upregulated in cancer cells cocultured with mature adipocytes; meanwhile, their expression levels in cancer cells cocultured with adipocytes were reduced by adipsin knockout (Cfd KO) or a competitive inhibitor of CFD. Tumor growth and distant metastasis of mammary cancer cells were significantly suppressed when syngeneic mammary cancer cells were transplanted into Cfd KO mice. Histological analyses revealed reductions in capsular formation and tumor invasion at the cancer-adipocyte interface in the mammary tumors formed in Cfd KO mice. These findings indicate that adipsin-dependent adipocyte maturation may play an important role in adipocyte-cancer cell interaction and breast cancer progression. [ABSTRACT FROM AUTHOR]

Cancer refers to the proliferation and multiplication of aberrant cells inside the human body, characterized by their capacity to proliferate and infiltrate various anatomical regions. Numerous biochemical pathways and signaling molecules have an impact on the cancer auto biogenesis process. The regulation of crucial cellular processes necessary for cell survival and proliferation, which are triggered by phytochemicals, is significantly influenced by signaling pathways. These pathways or components are regulated by phytochemicals. Medicinal plants are a significant reservoir of diverse anticancer medications employed in chemotherapy. The anticancer effects of phytochemicals are mediated by several methods, including induction of apoptosis, cessation of the cell cycle, inhibition of kinases, and prevention of carcinogenic substances. This paper analyzes the phytochemistry of seven prominent plant constituents, namely, alkaloids, tannins, flavonoids, phenols, steroids, terpenoids, and saponins, focusing on the involvement of the MAPK/ERK pathway, TNF signaling, death receptors, p53, p38, and actin dynamics. Hence, this review has examined a range of phytochemicals, encompassing their structural characteristics and potential anticancer mechanisms. It has underscored the significance of plant-derived bioactive compounds in the prevention of cancer, utilizing diverse molecular pathways. In addition, this endeavor also seeks to incentivize scientists to carry out clinical trials on anticancer medications derived from plants. [ABSTRACT FROM AUTHOR]

Nano-sized titanium dioxide particles (TiO2 NPs) are a high-production volume nanomaterial widely used in the paints, cosmetics, food and photovoltaics industry. However, the potential carcinogenic effects of TiO2 NPs in the lung are still unclear despite the vast number of in vitro and in vivo studies investigating TiO2 NPs. Here, we systematically reviewed the existing in vitro and in vivo mechanistic evidence of TiO2 NP lung carcinogenicity using the ten key characteristics of carcinogens for identifying and classifying carcinogens. A total of 346 studies qualified for the quality and reliability assessment, of which 206 were considered good quality. Using a weight-of-evidence approach, these studies provided mainly moderate to high confidence for the biological endpoints regarding genotoxicity, oxidative stress and chronic inflammation. A limited number of studies investigated other endpoints important to carcinogenesis, relating to proliferation and transformation, epigenetic alterations and receptor-mediated effects. In summary, TiO2 NPs might possess the ability to induce chronic inflammation and oxidative stress, but it was challenging to compare the findings in the studies due to the wide variety of TiO2 NPs differing in their physicochemical characteristics, formulation, exposure scenarios/test systems, and experimental protocols. Given the limited number of high-quality and high-reliability studies identified within this review, there is a lack of good enough mechanistic evidence for TiO2 NP lung carcinogenicity. Future toxicology/carcinogenicity research must consider including positive controls, endotoxin testing (where necessary), statistical power analysis, and relevant biological endpoints, to improve the study quality and provide reliable data for evaluating TiO2 NP-induced lung carcinogenicity. [ABSTRACT FROM AUTHOR]

Congenital cytomegalovirus (cCMV) infection is the most common cause of neurodevelopmental sequelae in the United States (US). The most common long-term disability associated with cCMV is sensorineural hearing loss (SNHL). Among children with cCMVassociated SNHL, over 40% will pass their newborn hearing screen (NHS). Therefore, to maximize the identification of infants at risk for SNHL, there is a strong rationale for universal cCMV screening. Early identification of cCMV also allows for the timely commencement of antiviral therapies for some infants, which in turn can improve clinical outcomes. Congenital infection must be diagnosed in the newborn infant in the first 21 days of life since demonstration of CMV infection beyond this time point commonly reflects postnatal acquisition, typically from breastfeeding. Although many advocates are enthusiastic about universal cCMV screening (1-3), other experts express hesitancy in embracing such a policy recommendation until there is more evidence of cost-effectiveness. Moreover, since most infants with cCMV are asymptomatic and have a good prognosis for normal neurodevelopmental outcomes, there is concern that universal screening may raise undue anxiety for parents of infants with asymptomatic cCMV infection (4). This review considers the pros and cons of different cCMV screening approaches, emphasizing enhancing awareness of new and emerging approaches for neonatologists in clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Ochratoxin A (OTA), a nephrotoxic mycotoxin categorized as a possible carcinogenic agent, is a current problem in the cheese manufacturing industry. The main OTA producers are Penicillium nordicum and Penicillium verrucosum. Therefore, we aimed to investigate different cheese ripening phases to hinder OTA production. We elaborated cheese analogues, inoculated both fungal species, and performed two different ripening phases, at 10 and 15 °C. Despite the fact that both were able to grow, they did not express genes related to OTA production, and no OTA was detected during two weeks of ripening. Therefore, we show that, when the first phases of ripening are maintained at <15 °C, the possibility of OTA production is dramatically minimized. This information is of utmost importance for industries to enhance the safety of their cheese products, which positively impacts human health. A lack of control of the technological abiotic parameters apparent during cheese manufacture, including temperature and relative humidity, results in this dairy product being prone to mold contamination. Sometimes, inoculant molds are used to obtain the characteristic sensory properties of this type of product. However, during the maturation process, some unwanted molds can colonize the ripening cheese and produce mycotoxins. Mycotoxigenic molds such as Penicillium nordicum and Penicillium verrucosum can colonize ripened cheeses, contaminating them with ochratoxin A (OTA), a nephrotoxic 2B toxin. Thus, the presence of OTA in cheeses could represent a hazard to consumers' health. This study has evaluated the growth and OTA production of P. nordicum and P. verrucosum on a cheese analogue under simulated ripening conditions of 10 and 15 °C and 0.96 water activity (aw). Ecophysiological, molecular, and analytical tools assessed the mold growth, gene expression, and OTA production under these environmental conditions. Both species were able to effectively colonize the cheese under these ripening conditions. However, neither species expressed the otapks and otanps biosynthetic genes or produced phenotypic OTA. Therefore, these results suggest a relatively low risk of exposure to OTA for consumers of this type of cheese product. The conditions used were thus appropriate for cheese ripening to minimize the potential for contamination with such mycotoxins. An appropriate adjustment of the technological ripening parameters during such cheese manufacture could contribute to OTA-free cheeses. [ABSTRACT FROM AUTHOR]

N-nitrosodimethylamine (NDMA) is a potentially carcinogenic byproduct of disinfecting drinking water. NDMA has been classified as a Group B2 carcinogen by the U.S. Environmental Protection Agency (EPA). The pathway of NDMA formation during chlorination has been proposed; however, it is still necessary to identify the most influential factor in this process. The objective of this study was to compare the factors and conditions that lead to the formation of NDMA from dimethylamine (DMA) to identify the primary factors responsible for the occurrence of this compound in drinking water. The study examined the formation of NDMA in chlorinated water under seven different conditions, considering three factors (NO2−, NO3−, and NH3). All factors were maintained at their actual concentrations in tap or surface water. The highest levels of NDMA were observed at pH 6 when NO3− and NH3 were present, with concentrations of 22.7 ng/L and 9.79 ng/L, respectively. At pH 6, NDMA levels were observed to be 22 times higher than at pH 8. Chlorine alone was not sufficient to convert DMA to NDMA within a short period of time, specifically at least 5 h, in the absence of other factors. The concentration of NDMA increased to 41.6 ng/L in the presence of NH3. After 16 h, the presence of NO3− led to a gradual increase in NDMA levels to 19.0 ng/L. However, no further increase was observed at this point. The findings suggest that NO3− and NH3 are important factors of NDMA in chlorinated drinking water. Although previous mechanisms have not given much attention to these factors, they are expected to play a significant role in the formation of nitrosamines in both natural water and drinking water. Controlling the factors or pH appeared to be crucial for managing NDMA formation, and further research on reducing N-nitrosamines is necessary. [ABSTRACT FROM AUTHOR]

A modular strategy is described for the testing and assessment (MoSt) of non-genotoxic carcinogenicity (NGTxC) that is suitable for regulatory applications. It utilizes and builds upon work conducted by the OECD expert group on NGTxC. The approach integrates relevant test methods from the molecular- to cellular- and further to tissue level, many of which have been recently reviewed. Six progressive modules are included in the strategy. Advice is provided for the iterative selection of the next appropriate test method within each step of the strategy. Assessment is completed by a weight of evidence conclusion, which integrates the different streams of modular information. The assessment method gives higher weight to findings that are mechanistically linked with biological relevance to carcinogenesis. With a focus on EU-REACH, and pending upon successful test method validation and acceptance, this will also enable the MoSt for NGTxC to be applied for regulatory purposes across different regulatory jurisdictions. [ABSTRACT FROM AUTHOR]

Oestrogen plays a crucial physiological role in both women and men. It regulates reproductive functions and maintains various non-reproductive tissues through its receptors, such as oestrogen receptor 1/oestrogen receptor α (ESR1/Erα), oestrogen receptor 2/oestrogen receptor β (ESR2/Erβ), and G protein-coupled oestrogen receptor 1 (GPER). This hormone is essential for the proper functioning of women's ovaries and uterus. Oestrogen supports testicular function and spermatogenesis in men and contributes to bone density, cardiovascular health, and metabolic processes in both sexes. Nuclear receptors Er-α and Er-β belong to the group of transcription activators that stimulate cell proliferation. In the environment, compounds similar in structure to the oestrogens compete with endogenous hormones for binding sites to receptors and to disrupt homeostasis. The lack of balance in oestrogen levels can lead to infertility, cancer, immunological disorders, and other conditions. Exogenous endocrine-active compounds, such as bisphenol A (BPA), phthalates, and organic phosphoric acid esters, can disrupt signalling pathways responsible for cell division and apoptosis processes. The metabolism of oestrogen and its structurally similar compounds can produce carcinogenic substances. It can also stimulate the growth of cancer cells by regulating genes crucial for cell proliferation and cell cycle progression, with long-term elevated levels linked to hormone-dependent cancers such as breast cancer. Oestrogens can also affect markers of immunological activation and contribute to the development of autoimmune diseases. Hormone replacement therapy, oral contraception, in vitro fertilisation stimulation, and hormonal stimulation of transgender people can increase the risk of breast cancer. Cortisol, similar in structure to oestrogen, can serve as a biomarker associated with the risk of developing breast cancer. The aim of this review is to analyse the sources of oestrogens and their effects on the endogenous and exogenous process of homeostasis. [ABSTRACT FROM AUTHOR]

Hypoxia is a critical factor contributing to a poor prognosis and challenging glioma therapy. Previous studies have indicated that hypoxia drives M2 polarization of macrophages and promotes cancer progression in various solid tumors. However, the more complex and diverse mechanisms underlying this process remain to be elucidated. Here, we aimed to examine the functions of hypoxia in gliomas and preliminarily investigate the underlying mechanisms of M2 macrophage polarization caused by hypoxia. We found that hypoxia significantly enhances the malignant phenotypes of U87 and U251 cells by regulating glycolysis. In addition, hypoxia mediated accumulation of the glycolysis product [lactic acid (LA)], which is subsequently absorbed by macrophages to induce its M2 polarization, and this process is reverted by both the glycolysis inhibitor and silenced monocarboxylate transporter (MCT-1) in macrophages, indicating that M2 macrophage polarization is associated with the promotion of glycolysis by hypoxia. Interestingly, we also found that hypoxia mediated LA accumulation in glioma cells upon uptake by macrophages upregulates H3K18La expression and promotes tumor necrosis factor superfamily member 9 (TNFSF9) expression in a histone-lactylation-dependent manner based on the results of chromatin immunoprecipitation sequencing (ChIP seq) enrichment analysis. Subsequent in vitro and in vivo experiments further indicated that TNFSF9 facilitated glioma progression. Mechanistically, hypoxia-mediated LA accumulation in glioma cells is taken up by macrophages and then induces its M2 macrophage polarization by regulating TNFSF9 expression via MCT-1/H3K18La signaling, thus facilitating the malignant progression of gliomas. NEW & NOTEWORTHY: Our study revealed that hypoxia induces the production of LA accumulation through glycolysis in glioma cells, which is subsequently absorbed by macrophages and leads to its M2 polarization via the MCT-1/H3K18La/TNFSF9 axis, ultimately significantly promoting the malignant progression of glioma cells. These findings are novel and noteworthy as they provide insights into the connection between energy metabolism and epigenetics in gliomas. [ABSTRACT FROM AUTHOR]

KRAS mutations linked with cancer. Flavonoids were docked against KRAS G12C and G12D receptors. Abyssinone III, alpha naphthoflavone, beta naphthoflavone, abyssinone I, abyssinone II and beta naphthoflavone, genistin, daidzin showed good docking scores against KRAS G12C and G12D receptors, respectively. The MD simulation data revealed that Rg, RMSD, RMSF, and SASA values were within acceptable limits. Alpha and beta naphthoflavone showed good binding energies with KRAS G12C and G12D receptors. DFT and MEP analysis highlighted the nucleophilic and electrophilic zones of best-docked flavonoids. A novel avenue for the control of KRAS G12C and G12D mutations is made possible by flavonoids. In the present study, we computationally established the role of flavonoids as KRAS G12C and G12D inhibitors. Initially we selected 93 flavonoids and docked against 8AFB (KRAS G12C) and 7RT1 (KRAS G12D) using Sotorasib and MRTX 1133 as standards. A 100 ns MD simulation revealed that the radius of gyration, RMSD, RMSF, and SASA values were within acceptable limits and that there were a greater number of donors and acceptors for hydrogen bonds. In addition to the KRAS G12C 8AFB receptor, the maximum binding energy was shown by alpha Naphthoflavone (−26.471 kJ/mol), and for the KRAS G12D 7RT1 receptor, the maximum binding energy was shown by beta Naphthoflavone (−15.433 kJ/mol). FMO and MEP analysis data highlighted the best-docked flavonoids' potential areas for nucleophilic and electrophilic attacks. ADMET properties have been calculated and provide safe use and low toxicity for both aquatic and non-aquatic species. [ABSTRACT FROM AUTHOR]

Background and Purpose: It is well acknowledged that tobacco‐derived lung carcinogens can induce lung injury and even lung cancer through a complex mechanism. MicroRNAs (MiRNAs) are differentially expressed in tobacco‐derived carcinogen nicotine‐derived nitrosamine ketone (NNK)‐treated A/J mice. Experimental Approach: RNA sequencing was used to detect the level of long non‐coding RNAs (lncRNAs). Murine and human lung normal and cancer cells were used to evaluate the function of lncRNA XIST and miR‐328‐3p in vitro, and NNK‐treated A/J mice were used to test their function in vivo. In vivo levels of miR‐328‐3p and lncRNA XIST were analysed, using in situ hybridization. miR‐328‐3p agomir and lncRNA XIST‐specific siRNA were used to manipulate in vivo levels of miR‐328‐3p and lncRNA XIST in A/J mice. Key Results: LncRNA XIST was up‐regulated in NNK‐induced lung injury and dominated the NNK‐induced ectopic miRNA expression in NNK‐induced lung injury both in vitro and in vivo. Either lncRNA XIST silencing or miR‐328‐3p overexpression exerted opposing effects in lung normal and cancer cells regarding cell migration. LncRNA XIST down‐regulated miR‐328‐3p levels as a miRNA sponge, and miR‐328‐3p targeted the 3′‐UTR of FZD7 mRNA, which is ectopically overexpressed in lung cancer patients. Both in vivo lncRNA XIST silencing and miR‐328 overexpression could rescue NNK‐induced lung injury and aberrant overexpression of the lung cancer biomarker CK19 in NNK‐treated A/J mice. Conclusions and Implications: Our results highlight the promotive effect of lncRNA XIST in NNK‐induced lung injury and elucidate its post‐transcriptional mechanisms, indicating that targeting lncRNA XIST/miR‐328‐3p could be a potential therapeutic strategy to prevent tobacco carcinogen‐induced lung injury in vivo. [ABSTRACT FROM AUTHOR]

Heterocyclic aromatic amines (HAAs) are a class of carcinogenic substances formed during thermal processing of meat foods. Natural exogenous additives have been widely used in the food processing industry due to their own antioxidant activity, and researchers have developed methods to inhibit the formation of HAAs through the addition of exogenous additives, including synthetic antioxidants, plant extracts, spices, organosulfur compounds, cellulose fibers and some new inhibitors. Although much progress has been made in the study of exogenous additives, the mechanism of inhibition by different additives remains unclear. Here, we comprehensively summaries the inhibitory effects of exogenous additives on the formation of HAAs and their key inhibitory mechanisms, thereby reducing the formation of harmful compounds and improving food safety and nutritional value. We hope that this review will provide a bird's eye view of the inhibition of HAAs, which will be useful for further research on practical applications. Schematic illustration of exogenous additives applied to inhibit HAAs formation and involved effect mechanism [ABSTRACT FROM AUTHOR]

This article considers the current worldwide cancer epidemic as shaped through complex somatechnical intra-actions between the intimately fleshy suffering of individual bodies and structural violence exerted through carcinogenic necrotechnologies such as pesticides. Additionally, it unpacks the epistemologies of ignorance that characterise contemporary cancer imaginaries in the west by reflecting on how they operate through the widespread deployment of warfare metaphors; metaphors that, in the twenty-first century, have morphed into 'war against cancer-as-terror(ist)'- images. United States oncologist Siddhartha Mukherjee's bestselling book, The Emperor of All Maladies: A Biography of Cancer (2011) – also the winner of the Guardian's non-fiction book award – figures as a nodal point for the ways in which mainstream western cancer narratives and biomedical models obscure the links between cancer and what anthropologist-chemist Anastasia Karakasidou calls chemical modernity; that is, the global spread of carcinogens as a consequence of the worldwide racial capitalist transformations of agriculture and production through chemicalisation. Investigating how epistemologies of ignorance work at the levels of cancer biology, cancer treatment, and environmental carcinogenesis, this article at the same time also demonstrates how the somatechnical lens makes it possible to analyse the intertwined operations of violence, power, technologies, and bodies at all of these levels. This analysis is then complemented by a contemplation of the conative vitality of bodily matter that ontologically accounts for the chiasmatic two-way process between techné and soma that is central to a somatechnical understanding of cancerous embodiment. This article also uses autobiographical material to reflect upon the ways in which epistemologies of ignorance and their matching stories of cancer as natural pathology/enemy/doppelgänger/terrorist are nourished at the individual level of experience of cancer patients and their companions and carers. [ABSTRACT FROM AUTHOR]

BACKGROUND: Nail salon technicians are susceptible to potential exposure to a diverse array of hazardous chemicals in the form of dust or vapors. One of the main routes of exposure is dermal contact. OBJECTIVE: The aim of present study was to health risk assessment of dermal exposure to dust containing heavy metals in nail salon technicians. METHODS: Dust sampling was done on the work surface of 20 available nail salon technicians. The concentration of five metals including cadmium, lead, chromium, nickel, and manganese were determined using ICP-MS. Afterwards, the United States Environmental Protection Agency (USEPA) guideline was used to estimate the potential health risks, including carcinogenic and non-carcinogenic risks, associated with the analyzed metals. RESULTS: Results indicated the mean concentrations of Pb, Cd, Ni, Cr and Mn were 0.7953±0.4373, 0.0952±0.0264, 0.7666±0.8629, 0.4900±0.5994 and 1.134±0.4736, respectively. The hazard quotient (HQ) of all metals was within the permissible value, while hazard index (HI) was greater than 1. The probability of cancer risk (CR) resulting from dermal exposure to Ni, Cd and Cr exceeded the acceptable risk levels (10-6–10–4), but CR calculated for Pb was less than allowable value. CONCLUSION: Implementation of engineering controls such as downdraft vented nail tables and portable source capture systems is necessary. Besides, the use of personal protective equipment such as disposable nitrile gloves, N95 respirator masks, and ensuring proper training on safe work practices is recommended. [ABSTRACT FROM AUTHOR]

Purpose: To assess the prevalence and subtypes of Human Papillomavirus (HPV) in Ocular Surface Squamous Neoplasia (OSSN) in Human Immunodeficiency Virus (HIV) positive and negative patients in South Africa. Basic procedures: This study was a single center retrospective cross-sectional study, conducted at Tygerberg Hospital, Western Cape, South Africa. We assessed 63 histopathologically confirmed OSSN formalin-fixed paraffin-embedded (FFPE) tissue blocks from 2015–2023. The presence of HPV was determined using the Hybrispot Direct Flow Chip Kit. Corresponding clinical data was retrieved from the National Health Laboratory Service (NHLS) central data warehouse. Main findings: Of the confirmed OSSN samples, 66.7% tested positive for HPV (95% confidence interval [CI] 54–77.3%). Of the 42 HPV positive samples, 38 (90.5%) had one or more known genotypes detected and 4 had unknown genotypes. The most prevalent subtypes were HPV 11, 16 and 18 (found in 61.9%, 52.4% and 33.3% of HPV positive samples respectively). 88.9% of the lesions biopsied were from HIV positive patients, of whom 56.4% had a CD4 + count of < 200 cells/µL. A lower median CD4 + count was detected among HIV positive patients with invasive squamous cell carcinoma compared to those with moderate dysplasia (p < 0.0198). Conclusions: There is a high prevalence of HPV in OSSN in South Africa. Certain subtypes namely, 11, 16, 18, 31, 33 and 35 may be more carcinogenic. HIV with HPV co-infection may be linked as a causative factor in the development of OSSN. [ABSTRACT FROM AUTHOR]

Background Incidence of early-onset colorectal cancer (CRC) has increased globally in recent decades. We examined early-onset CRC incidence trends worldwide for potential cohort effects, defined as changes associated with time of birth (eg, early-life exposure to carcinogens), and period effects, defined as changes associated with calendar periods (eg, screening programs). Methods We obtained long-term incidence data for early-onset CRC diagnosed in patients aged 20 to 49 years through the year 2012 for 35 countries in the Cancer Incidence in Five Continents database. We used a smoothing method to help compare cohort and period trends of early-onset CRC and used an age-period-cohort model to estimate cohort and period effects. Results Cohort effects had a more dominant role than period effects in the early-onset CRC incidence in Shanghai (China), the United Kingdom, Australia, New Zealand, Canada, the United States, and Osaka (Japan). The smoothed trends show the specific birth cohorts when early-onset CRC began to increase: the 1940s-1950s birth cohorts in the United States; the 1950s-1960s birth cohorts in other Western countries; the 1960s birth cohorts in Osaka; and the 1970s-1980s birth cohorts in Shanghai. Such increases occurred earlier for early-onset cancers of the rectum than of the colon. For the other countries, the results were less clear. Conclusions Recent birth cohorts may have been exposed to risk factors different from earlier cohorts, contributing to increased early-onset CRC incidence in several developed countries or regions in the West and Asia. Such increases began in earlier birth cohorts in Western countries than in developed regions of Asia. [ABSTRACT FROM AUTHOR]

The International Agency for Research on Cancer has classified N‐nitrosodiethylamine (NDEA) as a possible carcinogen and mutagenic substances, placing it in category 2A of compounds that are probably harmful to humans. It is found in nature and tobacco smoke, along with its precursors, and is also synthesized endogenously in the human body. The oral or parenteral administration of a minimal quantity of NDEA results in severe liver and kidney organ damage. The NDEA required bioactivation by CYP450 enzyme to form DNA adduct in the alkylation mechanism. Thus, this bioactivation directs oxidative stress and injury to cells due to the higher formation of reactive oxygen species and alters antioxidant system in tissues, whereas free radical scavengers guard the membranes from NDEA‐directed injury in many enzymes. This might be one of the reasons in the etiology of cancer that is not limited to a certain target organ but can affect various organs and organ systems. Although there are various possible approaches for the treatment of NDEA‐induced cancer, their therapeutic outcomes are still very dismal. However, several precautions were considered to be taken during handling or working with NDEA, as it considered being the best way to lower down the occurrence of NDEA‐directed cancers. The present review was designed to enlighten the general guidelines for working with NDEA, possible mechanism, to alter the antioxidant line to cause malignancy in different parts of animal body along with its protective agents. Thus, revelation to constant, unpredictable stress situations even in common life may remarkably augment the toxic potential through the rise in the oxidative stress and damage of DNA. N‐Nitrosodiethylamine (NDEA) is a potential carcinogen and mutagen. Their carcinogenic action is not limited to a certain target organ but can affect various organs and organ systems. It induces oxidative stress and cellular injury due to higher formation of reactive oxygen species and alters antioxidant system in the tissues. The present review was designed to enlighten the general guidelines for working with NDEA, possible mechanism, to alter antioxidant line to cause malignancy in different parts of animal body along with its protective agents. [ABSTRACT FROM AUTHOR]

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a devastating disease most often associated with tobacco consumption that induces a field of mutations from which a tumor arises. Identification of ways to prevent the emergence of cancer in high-risk patients is an ultimate goal for combatting all types of cancer, including OSCC. METHODS: Our study employs a mouse model of tongue carcinogenesis induced by tobacco carcinogen mimetic, 4-nitroquinoline 1-oxide (4NQO), to establish tongue dysplasia and OSCC. We use conventional histology, immunohistochemistry, multispectral imaging, mass cytometry, novel cell lines, pharmaceutical inhibition of PI3Kγ, T-cell suppression assays and mouse transplant models in our functional experimentation. RESULTS: In our study, we identify Ly6G+ granulocytes as the most abundant immune cell type in a model of tongue carcinogenesis induced by tobacco carcinogen mimetic 4NQO. Targeting Ly6G+ granulocytes with a pharmacologic inhibitor of PI3Kγ, an isoform of PI3K exclusively expressed by myeloid cells, resulted in reduced tongue dysplasia severity, and reduced rates of OSCC. Importantly, we performed functional assays with the Ly6G+ granulocytes induced in cell line models of 4NQO carcinogenesis to demonstrate that these granulocytes have increased polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) activity against T-cell proliferation and these PMN-MDSCs play a functional role in promoting tumor formation by inhibiting tumor regression in a PI3Kγ-dependent manner. CONCLUSIONS: Overall, our data suggest that recruitment of PMN-MDSCs to sites of dysplasia is critical to immune suppression of CD8 T cells, thereby permitting malignancy, and PI3Kγ inhibitors are one mechanism to reduce PMN-MDSC recruitment, immunosuppression and tumorigenesis in OSCC.