The Cytotoxic Activity and Metabolic Profiling of Hyptis rhomboidea Mart. et Gal.

Many naturally occurring chemical metabolites with significant cytotoxic activities have been isolated from medicinal plants and have become the leading hotspot of anti-cancer research in recent years. Hyptis rhomboidea Mart. et Gal is used as a folk medicine in South China to treat or assist in the treatment of liver disease, ulcers, and edema. But its chemical constituents have not been fully investigated yet. This study aimed to assess the cytotoxicity of H. rhomboidea, which was chemically characterized by chromatography-mass spectrometry methods. The results showed that the 95% ethanol extract of H. rhomboidea has marked inhibitory effects on five human cancer cell lines (HL-60, A549, SMMC-7721, MDA-MB-231, and SW480), with IC50 values ranging from 15.8 to 40.0 µg/mL. A total of 64 compounds were identified by ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and gas chromatograph-mass spectroscopy (GC-MS) analysis of H. rhomboidea crude extract. Among them, kaempferol, quercetin, rosmarinic acid, squalene, and campesterol were found to be abundant and might be the major metabolites involved to its bioactivity. The cytotoxic characterization and metabolite profiling of H. rhomboidea displayed in this research provides scientific evidence to support its use as medicinal properties.

Exposure to Dietary Glycidyl and 3-MCPD Fatty Acid Esters and Associated Burden of Cancer in Selected Asian and European Countries: A Review and Data Synthesis.

This study evaluated the health implications and oncological impact of consuming glycidyl esters (GE) and 3-monochloro-1,2-propanediol esters (3-MCPDE) in selected Asian and European populations. Data on dietary GE and 3-MCPDE were compiled from 10 studies conducted in China, Taiwan, Poland, and Spain, identified through a systematic search in PubMed and ScienceDirect databases from 2012 to 2022. Studies on food supplements and analytical methods were excluded from the analysis. Health metrics for these nations, spanning 2015 to 2019, were sourced from the Institute of Health Metrics and Evaluation, among others. A Monte Carlo Simulation was employed for data analysis. The results showed that "grains and grain products" was the most consumed food category (260.45-395.35 g/day), whereas "food for infants and children" was the least consumed (0.01-0.09 g/day). Additionally, "fats from animal or plant origin" had the highest contamination levels. While 3-MCPDE exposures remained within safe limits, median GE exposure correlated with an incidence of colon cancer ranging from 3.66 × 10-8 to 0.744%, lung cancer from 0.00256 to 0.287%, and breast cancer from 0.0262 to 2.42% within the study areas. This translated to a total cancer burden of 6.69 to 1020 Disability-Adjusted Life Years (DALYs) per 100 000 individuals. The population in China recorded the highest DALY rate (1,020), followed by Spain (30.2), Poland (19.7), and Taiwan (6.69). Projections suggest an uptick in GE-related cancer cases and associated burdens in the coming decades attributed to demographic shifts, ageing populations, and dietary changes. The study underscores the urgency of mitigating GE and 3-MCPDE food contamination, bolstering public health awareness, and establishing safety guidelines.

Scanning sample-specific miRNA regulation from bulk and single-cell RNA-sequencing data.

BACKGROUND: RNA-sequencing technology provides an effective tool for understanding miRNA regulation in complex human diseases, including cancers. A large number of computational methods have been developed to make use of bulk and single-cell RNA-sequencing data to identify miRNA regulations at the resolution of multiple samples (i.e. group of cells or tissues). However, due to the heterogeneity of individual samples, there is a strong need to infer miRNA regulation specific to individual samples to uncover miRNA regulation at the single-sample resolution level. RESULTS: Here, we develop a framework, Scan, for scanning sample-specific miRNA regulation. Since a single network inference method or strategy cannot perform well for all types of new data, Scan incorporates 27 network inference methods and two strategies to infer tissue-specific or cell-specific miRNA regulation from bulk or single-cell RNA-sequencing data. Results on bulk and single-cell RNA-sequencing data demonstrate the effectiveness of Scan in inferring sample-specific miRNA regulation. Moreover, we have found that incorporating the prior information of miRNA targets can generally improve the accuracy of miRNA target prediction. In addition, Scan can contribute to construct cell/tissue correlation networks and recover aggregate miRNA regulatory networks. Finally, the comparison results have shown that the performance of network inference methods is likely to be data-specific, and selecting optimal network inference methods is required for more accurate prediction of miRNA targets. CONCLUSIONS: Scan provides a useful method to help infer sample-specific miRNA regulation for new data, benchmark new network inference methods and deepen the understanding of miRNA regulation at the resolution of individual samples.

Phytocompounds and Nanoformulations for Anticancer Therapy: A Review.

Cancer is a complex disease that affects millions of people and remains a major public health problem worldwide. Conventional cancer treatments, including surgery, chemotherapy, immunotherapy, and radiotherapy, have limited achievements and multiple drawbacks, among which are healthy tissue damage and multidrug-resistant phenotype onset. Increasing evidence shows that many plants' natural products, as well as their bioactive compounds, have promising anticancer activity and exhibit minimal toxicity compared to conventional anticancer drugs. However, their widespread use in cancer therapy is severely restricted by limitations in terms of their water solubility, absorption, lack of stability, bioavailability, and selective targeting. The use of nanoformulations for plants' natural product transportation and delivery could be helpful in overcoming these limitations, thus enhancing their therapeutic efficacy and providing the basis for improved anticancer treatment strategies. The present review is aimed at providing an update on some phytocompounds (curcumin, resveratrol, quercetin, and cannabinoids, among others) and their main nanoformulations showing antitumor activities, both in vitro and in vivo, against such different human cancer types as breast and colorectal cancer, lymphomas, malignant melanoma, glioblastoma multiforme, and osteosarcoma. The intracellular pathways underlying phytocompound anticancer activity and the main advantages of nanoformulation employment are also examined. Finally, this review critically analyzes the research gaps and limitations causing the limited success of phytocompounds' and nanoformulations' clinical translation.

Triangle-toothed gear occlude-guided universal nanotechnology constructs 3D symmetric DNA polyhedra with high assembly efficiency for precision cancer therapy.

Chemotherapy is commonly used to treat malignant tumors. However, conventional chemotherapeutic drugs often cannot distinguish between tumor and healthy cells, resulting in adverse effects and reduced therapeutic efficacy. Therefore, zigzag-shaped gear-occlude-guided cymbal-closing (ZGC) DNA nanotechnology was developed based on the mirror-symmetry principle to efficiently construct symmetric DNA polyhedra. This nanotechnology employed simple mixing steps for efficient sequence design and assembly. A targeting aptamer was installed at a user-defined position using an octahedron as a model structure. Chemotherapeutic drug-loaded polyhedral objects were subsequently delivered into tumor cells. Furthermore, anticancer drug-loaded DNA octahedra were intravenously injected into a HeLa tumor-bearing mouse model. Assembly efficiency was almost 100 %, with no residual building blocks identified. Moreover, this nanotechnology required a few DNA oligonucleotides, even for complex polyhedrons. Symmetric DNA polyhedrons retained their structural integrity for 24 h in complex biological environments, guaranteeing prolonged circulation without drug leakage in the bloodstream and promoting efficient accumulation in tumor tissues. In addition, DNA octahedra were cleared relatively slowly from tumor tissues. Similarly, tumor growth was significantly inhibited in vivo, and a therapeutic outcome comparable to that of conventional gene-chemo combination therapy was observed. Moreover, no systemic toxicity was detected. These findings indicate the potential application of ZGC DNA nanotechnology in precision medicine.

Unraveling links between aging, circadian rhythm and cancer: Insights from evidence-based analysis.

Aging and circadian rhythms have been connected for decades, but their molecular interaction has remained unknown, especially for cancers. In this situation, we summarized the current research actuality and problems in this field using the bibliometric analysis. Publications in the PubMed and Web of Science databases were retrieved. Overall, there is a rising trend in the publication volume regarding aging and circadian rhythms in the field of cancer. Researchers from USA, Germany, Italy, China and England have greater studies than others. Top three publication institutions are University of California System, UDICE-French Research Universities and University of Texas System. Current research hotspots include oxidative stress, breast cancer, melatonin, cell cycle, calorie restriction, prostate cancer and NF-KB. In conclusion, results generated by bibliometric analysis indicate that many approaches involve in the complex interactions between aging and circadian rhythm in cancer. These established and emerging research directions guide our exploration of the regulatory mechanisms of aging and circadian rhythms in cancer and provide a reference for developing new research avenues.

Human effector CD8+ T cells with an activated and exhausted-like phenotype control tumour growth in vivo in a humanized tumour model.

BACKGROUND: Humanized tumour models could be particularly valuable for cancer immunotherapy research, as they may better reflect human-specific aspects of the interfaces between tumour and immune system of human cancer. However, endogenous antitumour immunity in humanized models is still largely undefined. METHODS: We established an autologous humanized mouse tumour model by using NSG mice reconstituted with human immune cells from hematopoietic progenitors and tumours generated from transformed autologous human B cells. We demonstrate growth of solid lymphoid tumours after subcutaneous implantation, infiltration by endogenous human immune cells and immunocompetence of the model. FINDINGS: We found human T cell subsets described in human cancer, including progenitor exhausted (Tpex), terminally exhausted (Tex-term) and tissue-resident (TRM) cells in tumour-bearing humanized mice with accumulation of Tex-term and TRM in the tumour. In addition, we identified tumour-reactive CD8+ T cells through expression of CD137. This subpopulation of de novo arising human CD137+ CD8+ T cells displayed a highly proliferative, fully activated effector and exhausted-like phenotype with enhanced expression of activation and exhaustion markers like PD-1, CD39, CD160, TIM-3, TIGIT and TOX, the senescence marker CD57 (B3GAT1) and cytolytic effector molecules such as PRF1, GZMH and NKG7. Moreover, these CD137+ CD8+ T cells exhibited tumour-specific clonal expansion and presented signature overlap with tumour-reactive CD8+ T cells described in human cancer. We demonstrate superior anticancer activity of this activated and exhausted-like human CD8+ T cell subset by adoptive transfer experiments using recipients bearing autologous human tumours. Mice adoptively transferred with CD137+ CD8+ T cells showed reduced tumour growth and higher CD8+ T cell tumour infiltration, correlating with control of human tumours. INTERPRETATION: We established an immunocompetent humanized tumour model, providing a tool for immunotherapy research and defined effective anticancer activity of human effector CD8+ T cells with an activated and exhausted-like phenotype, supporting clinical exploration of such cells in adoptive T cell therapies. FUNDING: Swiss Cancer Research foundation.

Generation of a Rat Monoclonal Antibody for Human PAICS, a de novo Purine Biosynthetic Enzyme.

Phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) is a de novo purine biosynthetic enzyme. It has been found to be overexpressed in various types of cancer and is related to cell proliferation, invasion, the epithelial-mesenchymal transition, and efficient tumor growth. In this study, we describe a rat monoclonal antibody (mAb) 6A10, which was generated as an antigen of human PAICS. This mAb was generated to interact with the N-terminal region of human PAICS and was found to recognize endogenous PAICS enzymes in several cancer cells. Our results also indicated that it can recognize monkey and dog PAICS, which possess the same amino acid sequence in the antigenic region as human PAICS, but it does not recognize rat and mouse PAICS. Furthermore, our data indicated that this mAb is suitable for immunoprecipitation and immunoblotting use for several cancer cell lines. We, therefore, anticipate that mAb 6A10 will be useful for functional analyses of human PAICS in several cancers and for diagnosis of malignant transformation.

LncRNA TUG1 and its Molecular Mechanisms in Human Cancer.

As lncRNAs have increasingly been investigated, they are no longer simply defined as RNAs with no transcription capability. Studies have identified significant associations between the abnormal expression of lncRNAs and human diseases, particularly the mechanisms by which lncRNAs play a part in cancers, which are of considerable attention to researchers. As a result of the complex spatial structure, the mechanisms of interaction of lncRNAs in cancer cells are also complicated and diversified. Among a series of lncRNAs, TUG1, which is now considered to be a very high-value lncRNA, has recently been identified to express abnormally in some malignancies, leading to different alterations in cancer cells proliferation, migration, invasion, apoptosis, and drug resistance, and hence promoting or inhibiting cancer progression. Current studies have implicitly indicated that TUG1 can be used as a therapeutic target for human cancers. However, the biological functions of TUG1 have been studied for a short period of time, and the complete molecular mechanism still needs to be clarified. Accordingly, this review focuses on the principal molecular mechanisms of TUG1 in human cancers and the specific mechanisms of action in different cancer development processes based on existing studies.

Noncanonical functions of telomerase and telomeres in viruses-associated cancer.

The cause of cancer is attributed to the uncontrolled growth and proliferation of cells resulting from genetic changes and alterations in cell behavior, a phenomenon known as epigenetics. Telomeres, protective caps on the ends of chromosomes, regulate both cellular aging and cancer formation. In most cancers, telomerase is upregulated, with the telomerase reverse transcriptase (TERT) enzyme and telomerase RNA component (TERC) RNA element contributing to the maintenance of telomere length. Additionally, it is noteworthy that two viruses, human papillomavirus (HPV) and Epstein-Barr virus (EBV), utilize telomerase for their replication or persistence in infected cells. Also, TERT and TERC may play major roles in cancer not related to telomere biology. They are involved in the regulation of gene expression, signal transduction pathways, cellular metabolism, or even immune response modulation. Furthermore, the crosstalk between TERT, TERC, RNA-binding proteins, and microRNAs contributes to a greater extent to cancer biology. To understand the multifaceted roles played by TERT and TERC in cancer and viral life cycles, and then to develop effective therapeutic strategies against these diseases, are fundamental for this goal. By investigating deeply, the complicated mechanisms and relationships between TERT and TERC, scientists will open the doors to new therapies. In its analysis, the review emphasizes the significance of gaining insight into the multifaceted roles that TERT and TERC play in cancer pathogenesis, as well as their involvement in the viral life cycle for designing effective anticancer therapy approaches.

The Cross-Talk of Non-coding RNAs and Inflammation in Human Cancer.

Despite advanced clinical treatment, the mortality rate of cancer patients is high. Recent studies have linked the development of cancer to inflammation. Many cancers are exacerbated by the emergence of inflammatory responses, and non-coding RNAs play an important role in inflammation. Non-coding RNAs include microRNAs, circular RNAs, long-chain noncoding RNAs, etc. The non-coding RNA regulatory network composed of microRNAs, circular RNAs and long-chain non-coding RNAs is involved in the regulatory process of multiple gene expression. They can act on various signaling pathways, such as wnt/ß-catenin, nuclear factorkappa B, phosphatidylinositol 3 kinase/ AKT, mitogen-activated protein kinase, and so on. These signaling pathways can control the occurrence of inflammatory response to some extent, such as regulating the expression of inflammatory cytokines (such as interleukin-6, interferongamma, tumor necrosis factor-α, and so on), making them upregulated or down-regulated. Therefore, it is important to study the role of non-coding RNAs in inflammation to contribute to the future of cancer.

In vitro and in silico study of eggplant extract on human cancer cell lines.

The aim of this research was to study the metabolite composition, antioxidative potential and cytotoxic activities of Solanum melongena fruit extracts. Phytochemical analyses of extracts were performed using LC-MS. Phenolic compounds were the major constituents present in the fruit extracts. Free radical scavenging activities were recorded and the highest activities were reported in methanolic extracts using DPPH (103.70 ± 2.75 EC50 µg/mL), ABTS (81.74 ± 3.64 EC50 µg/mL), and FRAP (22.39 ± 1.52 µmol TE/g) assays. Quantification has suggested the presence of delphinidin derivatives, and caffeic acid conjugates as major constituents of fruit extracts. The potential binding of these derivatives with human cell surface receptors was analysed using in silico analysis and validated for cytotoxic and apoptotic effects using in vitro studies on human cancer cell lines. The methanolic extract has shown the highest cytotoxic activity.

Therapeutic Potential of Clusterin Inhibition in Human Cancer.

Clusterin (CLU) protein is involved in various pathophysiological processes including carcinogenesis and tumor progression. In recent years, the role of the secretory isoform has been demonstrated in tumor cells, where it inhibits apoptosis and favors the acquisition of resistance to conventional treatments used to treat cancer. To determine the possible therapeutic potential of inhibiting this protein, numerous studies have been carried out in this field. In this article, we present the existing knowledge to date on the inhibition of this protein in different types of cancer and analyze the importance it could have in the development of new therapies targeted against this disease.

Role of HOX genes in cancer progression and their therapeutical aspects.

HOX genes constitute a family of evolutionarily conserved transcription factors that play pivotal roles in embryonic development, tissue patterning, and cell differentiation. These genes are essential for the precise spatial and temporal control of body axis formation in vertebrates. In addition to their developmental functions, HOX genes have garnered significant attention for their involvement in various diseases, including cancer. Deregulation of HOX gene expression has been observed in numerous malignancies, where they can influence tumorigenesis, progression, and therapeutic responses. This review provides an overview of the diverse roles of HOX genes in development, disease, and potential therapeutic targets, highlighting their significance in understanding biological processes and their potential clinical implications.

Effects of Reduced Extracellular Sodium Concentrations on Cisplatin Treatment in Human Tumor Cells: The Role of Autophagy.

Hyponatremia is the prevalent electrolyte imbalance in cancer patients, and it is associated with a worse outcome. Notably, emerging clinical evidence suggests that hyponatremia adversely influences the response to anticancer treatments. Therefore, this study aims to investigate how reduced extracellular [Na+] affects the responsiveness of different cancer cell lines (from human colon adenocarcinoma, neuroblastoma, and small cell lung cancer) to cisplatin and the underlying potential mechanisms. Cisplatin dose-response curves revealed higher IC50 in low [Na+] than normal [Na+]. Accordingly, cisplatin treatment was less effective in counteracting the proliferation and migration of tumor cells when cultured in low [Na+], as demonstrated by colony formation and invasion assays. In addition, the expression analysis of proteins involved in autophagosome-lysosome formation and the visualization of lysosomal areas by electron microscopy revealed that one of the main mechanisms involved in chemoresistance to cisplatin is the promotion of autophagy. In conclusion, our data first demonstrate that the antitumoral effect of cisplatin is markedly reduced in low [Na+] and that autophagy is an important mechanism of drug escape. This study indicates the role of hyponatremia in cisplatin chemoresistance and reinforces the recommendation to correct this electrolyte alteration in cancer patients.

Integrated In-Silico and In Vitro analysis to Decipher the contribution of bisphenol-A in cervical cancer.

Bisphenol A (BPA) is a synthetic chemical widely used as a monomer for producing polycarbonate plastics. The present investigation employed an in-silico approach to identify BPA-responsive genes and comprehend the biological functions affected using in vitro studies. A Comparative Toxicogenomics Database search identified 29 BPA-responsive genes in cervical cancer (CC). Twenty-nine genes were screened using published datasets, and thirteen of those showed differential expression between normal and CC samples. Protein-Protein Interaction Networks (PPIN) analysis identified BIRC5, CASP8, CCND1, EGFR, FGFR3, MTOR, VEGFA, DOC2B, WNT5A, and YY1 as hub genes. KM-based survival analysis identified that CCND, EGFR, VEGFA, FGFR3, DOC2B, and YY1 might affect CC patient survival. SiHa and CaSki cell proliferation, migration, and invasion were all considerably accelerated by BPA exposure. Changes in cell morphology, remodeling of the actin cytoskeleton, increased number and length of filopodia, elevated intracellular reactive oxygen species and calcium, and lipid droplet accumulation were noted upon BPA exposure. BPA treatment upregulated the expression of epithelial to mesenchymal transition pathway members and enhanced the nuclear translocation of CTNNB1. We showed that the enhanced migration and nuclear translocation of CTNNB1 upon BPA exposure is a calcium-dependent process. The present study identified potential BPA-responsive genes and provided novel insights into the biological effects and mechanisms affected by BPA in CC. Our study raises concern over the use of BPA.

Comprehensive analysis of the effects of the cuprotosis-associated gene SLC31A1 on patient prognosis and tumor microenvironment in human cancer.

Background: Solute carrier family 31 (copper transporter), member 1 (SLC31A1) is a key factor in maintaining intracellular copper concentration and an important factor affecting cancer energy metabolism. Therefore, exploring the potential biological function and value of SLC31A1 could provide a new direction for the targeted therapy of tumors. Methods: This study assessed gene expression levels, survival, clinicopathology, gene mutations, methylation levels, the tumor mutational burden (TMB), microsatellite instability (MSI), and the immune cell infiltration of SLC31A1 in pan-cancer using the Tumor Immune Estimation Resource 2.0 (TIMER2.0), Gene Expression Profiling Interactive Analysis (GEPIA), University of Alabama at Birmingham CANcer (UALCAN) data analysis portal, and cBioPortal databases. To further understand the potential biological mechanisms of SLC31A1 in different cancers, single-cell level sequencing and a Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) enrichment analysis of SLC31A1 were also performed. Finally, real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) were used to validate the expression of SLC31A1 in cancers, such as gastric cancer. Results: SLC31A1 was expressed in most cancer tissues. In kidney renal clear cell carcinoma (KIRC), the high expression of SLC31A1 was associated with good overall survival (OS), while in adrenocortical carcinoma (ACC), breast invasive carcinoma (BRCA), lower grade glioma (LGG), mesothelioma (MESO), and skin cutaneous melanoma (SKCM), the low expression of SLC31A1 was associated with good OS. The highest frequency of SLC31A1 amplification was observed in ACC. In addition, missense mutations accounted for a major portion of the mutation types. The truncation mutation S105Y may be a putative cancer driver. SLC31A1 affected methylation levels in cancer and was associated with the TMB, MSI, and the level of infiltration of various immune cells. Additionally, the single-cell sequencing results showed that SLC31A1 was associated with multiple biological functions in cancer. Finally, the SLC31A1 enrichment analysis revealed that the SLC31A1-related genes were mainly enriched in the mitochondrial matrix and envelope vesicles. The RT-qPCR and WB results were consistent with the predicted results. Conclusions: SLC31A1 may be a potential target related to cancer energy metabolism and may have prognostic value.

The Prognostic Value and Clinical Significance of lncRNA SNHG5 Expression in Patients with Multiple Malignancies: A Bioinformatic and Meta-analysis.

BACKGROUND: Long non-coding RNA small nucleolar RNA host gene 5 (lncRNA SNHG5) has been identified as both a promising target for treatment and a predictor of prognosis in diverse types of cancer. The objective of this study was to assess whether lncRNA SNHG5 expression can be utilized as a prognostic biomarker for human cancer. METHODS: To ensure a thorough search of the literature for relevant English studies published before July 2023, several databases were searched, including PubMed, Web of Science, ProQuest, Cochrane Library, and Google Scholar. The study evaluated the impact of lncRNA SNHG5 on the overall survival (OS) of cancer by calculating the pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CIs). To further confirm the accuracy of the findings, the study investigated the expression profile and prognostic significance of lncRNA SNHG5 through the use of GenomicScape, OncoLnc, Kaplan-Meier plotter, and GEPIA databases. RESULTS: In this study, 995 patients were examined across a total of fourteen original studies. The findings indicated that there was a significant relationship between heightened lncRNA SNHG5 expression and reduced OS, as evidenced by both univariate and multivariate analyses (HR = 1.89; 95% CI, 1.44-2.49; p < 0.001; HR = 3.97; 95% CI, 1.80-8.73; p < 0.001, respectively). Pooled OR analysis showed a significant association between over-expression of lncRNA SNHG5 with advanced histological grade (OR = 0.28; 95% CI, 0.11-0.71; p = 0.007), present lymph node metastasis (LNM; OR = 4.28; 95% CI, 2.47-7.43; p < 0.001), and smoking history (OR = 0.27; 95% CI, 0.15-0.49; p < 0.001). Bioinformatic databases confirmed that elevated SNHG5 expression was significantly linked to poor prognosis in cancer patients, including colorectal cancer (CRC), acute myeloid leukemia (AML), and esophageal adenocarcinoma (ESAD), and a longer OS in patients with uterine corpus endometrial carcinoma (UCEC). CONCLUSION: These results suggest that lncRNA SNHG5 may serve as an adverse prognostic biomarker in several human cancers. Further investigations are needed to better understand the underlying mechanisms that link lncRNA SNHG5 to multiple malignancies.

Alternative polyadenylation quantitative trait methylation mapping in human cancers provides clues into the molecular mechanisms of APA.

Genetic variants are involved in the orchestration of alternative polyadenylation (APA) events, while the role of DNA methylation in regulating APA remains unclear. We generated a comprehensive atlas of APA quantitative trait methylation sites (apaQTMs) across 21 different types of cancer (1,612 to 60,219 acting in cis and 4,448 to 142,349 in trans). Potential causal apaQTMs in non-cancer samples were also identified. Mechanistically, we observed a strong enrichment of cis-apaQTMs near polyadenylation sites (PASs) and both cis- and trans-apaQTMs in proximity to transcription factor (TF) binding regions. Through the integration of ChIP-signals and RNA-seq data from cell lines, we have identified several regulators of APA events, acting either directly or indirectly, implicating novel functions of some important genes, such as TCF7L2, which is known for its involvement in type 2 diabetes and cancers. Furthermore, we have identified a vast number of QTMs that share the same putative causal CpG sites with five different cancer types, underscoring the roles of QTMs, including apaQTMs, in the process of tumorigenesis. DNA methylation is extensively involved in the regulation of APA events in human cancers. In an attempt to elucidate the potential underlying molecular mechanisms of APA by DNA methylation, our study paves the way for subsequent experimental validations into the intricate biological functions of DNA methylation in APA regulation and the pathogenesis of human cancers. To present a comprehensive catalog of apaQTM patterns, we introduce the Pancan-apaQTM database, available at https://pancan-apaqtm-zju.shinyapps.io/pancanaQTM/.

Process optimization for gold nanoparticles biosynthesis by Streptomyces albogriseolus using artificial neural network, characterization and antitumor activities.

Gold nanoparticles (GNPs) are highly promising in cancer therapy, wound healing, drug delivery, biosensing, and biomedical imaging. Furthermore, GNPs have anti-inflammatory, anti-angiogenic, antioxidants, anti-proliferative and anti-diabetic effects. The present study presents an eco-friendly approach for GNPs biosynthesis using the cell-free supernatant of Streptomyces albogriseolus as a reducing and stabilizing agent. The biosynthesized GNPs have a maximum absorption peak at 540 nm. The TEM images showed that GNPs ranged in size from 5.42 to 13.34 nm and had a spherical shape. GNPs have a negatively charged surface with a Zeta potential of - 24.8 mV. FTIR analysis identified several functional groups including C-H, -OH, C-N, amines and amide groups. The crystalline structure of GNPs was verified by X-ray diffraction and the well-defined and distinct diffraction rings observed by the selected area electron diffraction analysis. To optimize the biosynthesis of GNPs using the cell-free supernatant of S. albogriseolus, 30 experimental runs were conducted using central composite design (CCD). The artificial neural network (ANN) was employed to analyze, validate, and predict GNPs biosynthesis compared to CCD. The maximum experimental yield of GNPs (778.74 µg/mL) was obtained with a cell-free supernatant concentration of 70%, a HAuCl4 concentration of 800 µg/mL, an initial pH of 7, and a 96-h incubation time. The theoretically predicted yields of GNPs by CCD and ANN were 809.89 and 777.32 µg/mL, respectively, which indicates that ANN has stronger prediction potential compared to the CCD. The anticancer activity of GNPs was compared to that of doxorubicin (Dox) in vitro against the HeP-G2 human cancer cell line. The IC50 values of Dox and GNPs-based treatments were 7.26 ± 0.4 and 22.13 ± 1.3 µg/mL, respectively. Interestingly, treatments combining Dox and GNPs together showed an IC50 value of 3.52 ± 0.1 µg/mL, indicating that they targeted cancer cells more efficiently.