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Genome steganography has emerged as a promising field for transmitting large amounts of data over an untrusted channel in the last two decades. DNA has many advantages over other multimedia cover mediums. Substitution is the most common approach to developing a DNA-based steganography algorithm. Components of the secret message are converted to DNA letters, which replace nucleotides in the cover sequence. The conversion is conducted through predetermined tables like binary coding rules and lookup/dictionary tables. These tables are static, limited to specific alphanumeric characters, and may compromise the hidden message if discovered by intruders. Most previously proposed algorithms adopt a simple sequential and ordered hiding pattern. This leads to poor utilization of the available hiding spots and creates a region of interest for attackers to apply steganalysis. In this paper, a novel DNA-based algorithm is proposed. Using two DNA sequences, primary and secondary, is the basis for this algorithm. Both sequences are segmented, where the primary sequence segments are for hiding the data, and the secondary sequence segments are for conveying the required information to find and extract the hidden data. Three enhanced tables are proposed: a modified ASCII table, a 4-bit binary coding rule table, and a two-tier lookup encoding table to convert the message to DNA form. The segmentation ensures that the hiding spots are randomly scattered across the primary cover DNA sequence, addressing the region of interest issue. The data is hidden in the cover using the least significant base substitutions. The result is an all-rounded algorithm that fulfills the desired performance measurements such as zero payloads, blindness, preserving functionality, high hiding capacity, low modification rate, and low cracking probability. [ABSTRACT FROM AUTHOR]

The human Vitamin K Epoxide Reductase Complex (hVKORC1), a key enzyme that converts vitamin K into the form necessary for blood clotting, requires for its activation the reducing equivalents supplied by its redox partner through thiol–disulphide exchange reactions. The functionally related molecular complexes assembled during this process have never been described, except for a proposed de novo model of a 'precursor' complex of hVKORC1 associated with protein disulphide isomerase (PDI). Using numerical approaches (in silico modelling and molecular dynamics simulation), we generated alternative 3D models for each molecular complex bonded either covalently or non-covalently. These models differ in the orientation of the PDI relative to hVKORC1 and in the cysteine residue involved in forming protein–protein disulphide bonds. Based on a comparative analysis of these models' shape, folding, and conformational dynamics, the most probable putative complexes, mimicking the 'precursor', 'intermediate', and 'successor' states, were suggested. In addition, we propose using these complexes to develop the 'allo-network drugs' necessary for treating blood diseases. [ABSTRACT FROM AUTHOR]

Improved understanding of TP53 biology and the clinicopathological features of TP53-mutated myeloid neoplasms has led to the recognition of TP53-mutated acute myeloid leukemia/myelodysplastic syndrome (TP53m AML/MDS) as a unique entity, characterized by dismal outcomes following conventional therapies. Several clinical trials have investigated combinations of emerging therapies for these patients with the poorest molecular prognosis among myeloid neoplasms. Although some emerging therapies have shown improvement in overall response rates, this has not translated into better overall survival, hence the notion that p53 remains an elusive target. New therapeutic strategies, including novel targeted therapies, immune checkpoint inhibitors, and monoclonal antibodies, represent a shift away from cytotoxic and hypomethylating-based therapies, towards approaches combining non-immune and novel immune therapeutic strategies. The triple combination of azacitidine and venetoclax with either magrolimab or eprenetapopt have demonstrated safety in early trials, with phase III trials currently underway, and promising interim clinical results. This review compiles background on TP53 biology, available and emerging therapies along with their mechanisms of action for the TP53m disease entity, current treatment challenges, and recently published data and status of ongoing clinical trials for TP53m AML/MDS. [ABSTRACT FROM AUTHOR]

Background: Thyroidectomy is increasingly performed for suspected malignancy. This cohort study aimed to identify genetic markers associated with malignancy and determine the molecular landscape of papillary thyroid carcinoma (PTC) through next-generation sequencing (NGS) in patients undergoing total thyroidectomy., Patients and Methods: Among 116 surgical candidates, 103 patients (age = 42.9 ± 13.7 years; Male: Female = 14:89) with benign or malignant thyroid nodules were eligible. Live thyroid tissue samples harvested intraoperatively with adequate DNA and RNA yield were subjected to NGS on the Illumina NovaSeq 6000 platform for genomic and transcriptomic analysis, respectively., Results: Histopathology comprised 20 malignant (19.4%) and 83 benign (80.6%) cases, including 16 PTC (15.5%) cases. On NGS, single nucleotide polymorphisms (SNPs) in NTRK1 at NC&#95;000001.11:156879016 on chromosome 1 and ALK at NC&#95;000002.12:29717663 on chromosome 2 were frequent in malignant lesions (p < 0.05). A SNP in ALK at NC&#95;000002.12:29193706 was consistently a homozygous alternate allele across the cohort. DNA-sequencing of PTC lesions identified recurrent somatic mutations in BRAF (100%), ALK (56.3%), RET (18.8%), PIK3CA (12.5%), NTRK1 (12.5%), NTRK2 (87.5%), NTRK3 (12.5%), NRAS (6.3%), and PTCH1 (31.3%) genes. RNA sequencing revealed novel fusion genes, including MKRN1-BRAF, RN7SL1-CDH1, IRF2BPL-MED12, MED12-IRF2BPL, CPM-MDM2, and AC005895.3-PDGFRB. In receiver operative characteristics analysis, the AUCs of ALK mutation predicting recurrence and metastases were 0.818 and 0.783., Conclusion: This Indian study identified novel somatic mutations and fusion genes in PTC, revealing a distinct genomic landscape with implications in precision diagnostics and personalized therapies. NGS with intraoperative live sampling shows promise in prognostication and therapeutic optimization of advanced/metastatic PTC cases., Trial Registration No: CTRI/2020/09/027607 dt 04/09/2020; REF/2020/08/036119., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

p53, a tumor suppressor protein, has a vital role in the regulation of the cell cycle, apoptosis, and DNA damage repair. The degradation of p53 is predominantly controlled by the murine double minute 2 (MDM2) protein, a ubiquitin E3 ligase. The overexpression or amplification of MDM2 is commonly observed in various human cancers bearing wild-type p53 alleles, leading to the rapid degradation of the p53 protein and the attenuation of p53 tumor suppression functions. Thus, a major effort in p53-based cancer therapy has been to research MDM2 antagonists that specifically stabilize and activate p53, leading to the suppression of tumor growth. However, despite numerous efforts to develop MDM2 antagonists, to date they have failed to reach clinical use, largely because of the cytotoxicity associated with these small molecules. This study used our newly designed structure-based virtual screening approach on a commercial compound library to identify a novel compound, CGMA-Q18, which directly binds to MDM2, leading to the activation of p53, the induction of apoptosis, and cell cycle arrest in cancer cells. Notably, CGMA-Q18 significantly inhibited tumor xenograft growth in nude mice without observable toxicity. These findings highlight our useful virtual screening protocol and CGMA-Q18 as a putative MDM2 antagonist., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Simple Summary: CHK2 has functions in DNA damage repair. Germline CHEK2 mutations impair these functions, increasing the risk of PTC. The aim of this study was to determine whether CHK2 and p53 expression in patients with a germline CHEK2 mutation in tumor tissue can serve as a prognostic marker for papillary thyroid cancer (PTC), and whether copy number aberrations in CHEK2 and TP53 correlate with the course of PTC. This study included 156 patients with PTC who had been selected from a group of 1547 people previously tested for the presence of CHEK2 mutations in their peripheral blood. Higher CHK2 expression was associated with poorer treatment responses and disease outcomes in PTC patients. Higher CHK2 expression and positive p53 together with a TP53 deletion could have potential as a prognostic marker of unfavorable disease outcomes in patients with germline truncating mutations in CHEK2. The aim of this study was to determine whether the expression of CHK2 and p53 in tumor tissue in carriers of germline CHEK2 mutations can serve as a prognostic marker for PTC, and whether CHEK2 and TP53 copy numbers correlates with the course of PTC disease. This study included 156 PTC patients previously tested for the presence of CHEK2. Clinicopathological features, treatment response, disease outcome, and germline mutation status of the CHEK2 gene were assessed with respect to CHK2 and p53 expression, and CHEK2 and TP53 gene copy statuses. In patients with and without a germline mutation in CHEK2 and with higher CHK2 expression, the chances of an excellent treatment response and no evidence of disease were lower than in patients without or with lower CHK2 expression. TP53 deletion was associated with angioinvasion. In patients with a truncating mutation, the chance of a CHEK2 deletion was higher than in patients with WT CHEK2 alone or those with WT CHEK2 and with the missense I157T mutation. Higher CHK2 expression was associated with poorer treatment responses and disease outcomes. Higher CHK2 expression and positive p53 together with a TP53 deletion could be a prognostic marker of unfavorable disease outcomes in patients with germline truncating mutations in CHEK2. [ABSTRACT FROM AUTHOR]

Ovarian cancer is a leading cause of death among women with gynecological cancers, and is often diagnosed at advanced stages, leading to poor outcomes. This review explores genetic aspects of high-grade serous, endometrioid, and clear-cell ovarian carcinomas, emphasizing personalized treatment approaches. Specific mutations such as TP53 in high-grade serous and BRAF/KRAS in low-grade serous carcinomas highlight the need for tailored therapies. Varying mutation prevalence across subtypes, including BRCA1/2, PTEN, PIK3CA, CTNNB1, and c-myc amplification, offers potential therapeutic targets. This review underscores TP53's pivotal role and advocates p53 immunohistochemical staining for mutational analysis. BRCA1/2 mutations' significance as genetic risk factors and their relevance in PARP inhibitor therapy are discussed, emphasizing the importance of genetic testing. This review also addresses the paradoxical better prognosis linked to KRAS and BRAF mutations in ovarian cancer. ARID1A, PIK3CA, and PTEN alterations in platinum resistance contribute to the genetic landscape. Therapeutic strategies, like restoring WT p53 function and exploring PI3K/AKT/mTOR inhibitors, are considered. The evolving understanding of genetic factors in ovarian carcinomas supports tailored therapeutic approaches based on individual tumor genetic profiles. Ongoing research shows promise for advancing personalized treatments and refining genetic testing in neoplastic diseases, including ovarian cancer. Clinical genetic screening tests can identify women at increased risk, guiding predictive cancer risk-reducing surgery. [ABSTRACT FROM AUTHOR]

Glycosphingolipids (GSLs) are a type of amphipathic lipid molecules consisting of hydrophobic ceramide backbone bound to carbohydrate moiety clustered in the cell surface microdomains named 'lipid rafts' and are known to participate in cell-cell communication as well as intra-cellular signaling, thereby facilitating critical normal cellular processes and functions. Over the past several decades, various GSLs have been reported to be aberrantly expressed in different cancers, many of which have been associated with their prognosis. The wide implication of MAPK signaling in controlling tumor growth, progression, and metastasis through activation of an upstream signaling cascade, often originating in the cell membrane, justifies the rationale for its plausible influence on MAPK signaling. This review highlights the role of GSLs and their metabolites in regulating different signaling pathways towards modulation of tumor cell growth, migration, and adhesion by interacting with various receptors [epidermal growth factor receptor (EGFR), and platelet derived growth factor receptor (PDGFR), and other receptor tyrosine kinases (RTKs)] leading to activation of the MAPK pathway. Furthermore, GSLs can influence the activity and localization of downstream signaling components in the MAPK pathway by regulating the activation state of kinases, which in turn, regulate the activity of MAPKs. Additionally, this review further consolidates the GSL-mediated modulation of MAPK pathway components through the regulation of gene expression. Finally, recent findings on GSL-MAPK crosstalk will be explored in this article for the identification of potential anti-cancer therapeutic targets., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cell cycle-dependent kinase 2 (CDK2) is located downstream of CDK4/6 in the cell cycle and regulates cell entry into S-phase by binding to Cyclin E and hyper-phosphorylating Rb. Proto-oncogene murine double minute 2 (MDM2) is a key negative regulator of p53, which is highly expressed in tumors and plays an important role in tumorigenesis and progression. In this study, we identified a dual inhibitor of CDK2 and MDM2, III-13, which had good selectivity for inhibiting CDK2 activity and significantly reduced MDM2 expression. In vitro results showed that III-13 inhibited proliferation of a wide range of tumor cells, regardless of whether Cyclin E1 (CCNE1) was overexpressed or not. The results of in vivo experiments showed that III-13 significantly inhibited proliferation of tumor cells and did not affect body weight of mice. The results of the druggability evaluation showed that III-13 was characterized by low bioavailability and poor membrane permeability when orally administered, suggesting the necessity of further structural modifications. Therefore, this study provided a lead compound for antitumor drugs, especially those against CCNE1-amplified tumor proliferation. [ABSTRACT FROM AUTHOR]

Hydrogen therapy shows great promise as a versatile treatment method for diseases associated with the overexpression of reactive oxygen and nitrogen species (RONS). However, developing an advanced hydrogen therapy platform that integrates controllable hydrogen release, efficient RONS elimination, and biodegradability remains a giant technical challenge. In this study, we demonstrate for the first time that the tungsten bronze phase H0.53WO3 (HWO) is an exceptionally ideal hydrogen carrier, with salient features including temperature-dependent highly-reductive atomic hydrogen release and broad-spectrum RONS scavenging capability distinct from that of molecular hydrogen. Moreover, its unique pH-responsive biodegradability ensures post-therapeutic clearance at pathological sites. Treatment with HWO of diabetic wounds in an animal model indicates that the solid-state atomic H promotes vascular formation by activating M2-type macrophage polarization and anti-inflammatory cytokine production, resulting in acceleration of chronic wound healing. Our findings significantly expand the basic categories of hydrogen therapeutic materials and pave the way for investigating more physical forms of hydrogen species as efficient RONS scavengers for clinical disease treatment. [ABSTRACT FROM AUTHOR]

Data-centric applications are pushing the limits of energy-efficiency in today’s computing systems, including those based on phase-change memory (PCM). This technology must achieve low-power and stable operation at nanoscale dimensions to succeed in high-density memory arrays. Here we use a novel combination of phase-change material superlattices and nanocomposites (based on Ge4Sb6Te7), to achieve record-low power density ≈ 5 MW/cm2 and ≈ 0.7 V switching voltage (compatible with modern logic processors) in PCM devices with the smallest dimensions to date (≈ 40 nm) for a superlattice technology on a CMOS-compatible substrate. These devices also simultaneously exhibit low resistance drift with 8 resistance states, good endurance (≈ 2 × 108 cycles), and fast switching (≈ 40 ns). The efficient switching is enabled by strong heat confinement within the superlattice materials and the nanoscale device dimensions. The microstructural properties of the Ge4Sb6Te7 nanocomposite and its high crystallization temperature ensure the fast-switching speed and stability in our superlattice PCM devices. These results re-establish PCM technology as one of the frontrunners for energy-efficient data storage and computing.Data-centric applications benefit from dense, low-power memory. Here the authors use a combination of chalcogenide superlattices and nanocomposites to achieve low switching voltage (0.7 V) and fast speed (40 ns) in 40-nm-scale phase-change memory. [ABSTRACT FROM AUTHOR]

Simple Summary: The chromosomal region 12q13-15 is rich in oncogenes (MDM2, CDK4, STAT6, DDIT3, and GLI1). Amplification of MDM2 and CDK4 genes can be detected in various mesenchymal and nonmesenchymal neoplasms. Therefore, gene amplification alone is not entirely specific for making a definitive diagnosis and requires the integration of clinical, radiological, morphological, and immunohistochemical findings. Despite the diagnostic implications that the overlap of genetic alterations in neoplasms with changes in genes within the 12q13-15 region could create, the discovery of coamplifications of MDM2 with CDK4 and GLI1 offers new therapeutic targets in neoplasms with MDM2/CDK4 amplification. In this review, we delve into the diagnosis and therapeutic implications of neoplasms with genetic alterations involving the chromosomal region 12q13-15, mainly MDM2, CDK4, and GLI1. The chromosomal region 12q13-15 is rich in oncogenes and contains several genes involved in the pathogenesis of various mesenchymal neoplasms. Notable genes in this region include MDM2, CDK4, STAT6, DDIT3, and GLI1. Amplification of MDM2 and CDK4 genes can be detected in various mesenchymal and nonmesenchymal neoplasms. Therefore, gene amplification alone is not entirely specific for making a definitive diagnosis and requires the integration of clinical, radiological, morphological, and immunohistochemical findings. Neoplasms with GLI1 alterations may exhibit either GLI1 rearrangements or amplifications of this gene. Despite the diagnostic implications that the overlap of genetic alterations in neoplasms with changes in genes within the 12q13-15 region could create, the discovery of coamplifications of MDM2 with CDK4 and GLI1 offers new therapeutic targets in neoplasms with MDM2/CDK4 amplification. Lastly, it is worth noting that MDM2 or CDK4 amplification is not exclusive to mesenchymal neoplasms; this genetic alteration has also been observed in other epithelial neoplasms or melanomas. This suggests the potential use of MDM2 or CDK4 inhibitors in neoplasms where alterations in these genes do not aid the pathological diagnosis but may help identify potential therapeutic targets. In this review, we delve into the diagnosis and therapeutic implications of tumors with genetic alterations involving the chromosomal region 12q13-15, mainly MDM2, CDK4, and GLI1. [ABSTRACT FROM AUTHOR]

Intrahepatic cholangiocarcinoma (ICC) is a relatively uncommon but highly aggressive primary liver cancer that originates within the liver. The aim of this study is to review the molecular profile of intrahepatic cholangiocarcinoma and its implications for prognostication and decision-making. This comprehensive characterization of ICC tumors sheds light on the disease's underlying biology and offers a foundation for more personalized treatment strategies. This is a narrative review of the prognostic and therapeutic role of the molecular profile of ICC. Knowing the molecular profile of tumors helps determine prognosis and support certain target therapies. The molecular panel in ICC helps to select patients for specific therapies, predict treatment responses, and monitor treatment responses. Precision medicine in ICC can promote improvement in prognosis and reduce unnecessary toxicity and might have a significant role in the management of ICC in the following years. The main mutations in ICC are in tumor protein p53 (TP53), Kirsten rat sarcoma virus (KRAS), isocitrate dehydrogenase 1 (IDH1), and AT-rich interactive domain-containing protein 1A (ARID1A). The rate of mutations varies significantly for each population. Targeting TP53 and KRAS is challenging due to the natural characteristics of these genes. Different stages of clinical studies have shown encouraging results with inhibitors of mutated IDH1 and target therapy for ARID1A downstream effectors. Fibroblast growth factor receptor 2 (FGFR2) fusions are an important target in patients with ICC. Immune checkpoint blockade can be applied to a small percentage of ICC patients. Molecular profiling in ICC represents a groundbreaking approach to understanding and managing this complex liver cancer. As our comprehension of ICC's molecular intricacies continues to expand, so does the potential for offering patients more precise and effective treatments. The integration of molecular profiling into clinical practice signifies the dawn of a new era in ICC care, emphasizing personalized medicine in the ongoing battle against this malignancy. [ABSTRACT FROM AUTHOR]

Cucurbitacin B (Cu B), a triterpenoid compound, has anti-inflammatory and antioxidant activities. Most studies only focus on the hepatoprotective activity of Cu B, and little effort has been geared toward exploring the effect of Cu B on the prostate. Our study identified that Cu B inhibited the proliferation of the benign prostatic hyperplasia epithelial cell line (BPH-1). At the molecular level, Cu B upregulated MDM2 and thrombospondin 1 (THBS1) mRNA levels. Immunocytochemistry results revealed that the protein expressions of p53 and MDM2 were upregulated in BPH-1 cells. Furthermore, Cu B upregulated THBS1 expression and downregulated COX-2 expression in the BPH-1 cell supernatant. Altogether, Cu B may inhibit prostate cell proliferation by activating the p53/MDM2 signaling cascade and downregulating the COX-2 expression. [ABSTRACT FROM AUTHOR]

The combination of trastuzumab and pertuzumab as first-line therapy in patients with HER2-positive breast cancer has shown significant clinical benefits compared to trastuzumab alone. However, despite initial therapeutic success, most patients eventually progress, and tumors develop acquired resistance and invariably relapse. Therefore, there is an urgent need to improve our understanding of the mechanisms governing resistance in order to develop targeted therapeutic strategies with improved efficacy. We generated four novel HER2-positive cell lines via prolonged exposure to trastuzumab and pertuzumab and determined their resistance rates. Long-term resistance was confirmed by a significant increase in the colony-forming capacity of the derived cells. We authenticated the molecular identity of the new lines via both immunohistochemistry for the clinical phenotype and molecular profiling of point mutations. HER2 overexpression was confirmed in all resistant cell lines, and acquisition of resistance to trastuzumab and pertuzumab did not translate into differences in ER, PR, and HER2 receptor expression. In contrast, changes in the expression and activity of other HER family members, particularly HER4, were observed. In the same vein, analyses of the receptor and effector kinase status of different cellular pathways revealed that the MAPK pathway may be involved in the acquisition of resistance to trastuzumab and pertuzumab. Finally, proteomic analysis confirmed a significant change in the abundance patterns of more than 600 proteins with implications in key biological processes, such as ribosome formation, mitochondrial activity, and metabolism, which could be relevant mechanisms in the generation of resistance in HER2-positive breast cancer. We concluded that these resistant BCCLs may be a valuable tool to better understand the mechanisms of acquisition of resistance to trastuzumab and pertuzumab-based anti-HER2 therapy. [ABSTRACT FROM AUTHOR]

The p53 tumor suppressor protein is best known as an activator of cell cycle arrest and apoptosis. Only a fraction of p53-activated genes encode proteins affecting cellular replication and various forms of cell death (apoptosis, ferroptosis, autophagy). The p53-regulated genes can be divided into so-called the core transcriptional program, which comprises genes activated in most cell types by most activators, and into the group of genes activated in in cell- or stress-specific manner. Activation of p53 occurs via the extensive set of posttranslational modifications, which adjust its stability, interaction with other transcription regulators, and its ability to form a tetramer. Surprisingly, in mouse models, the activation of the best-studied p53 target genes encoding the inhibitor of the cell cycle (CDKN1A) or the inducers of apoptosis (e.g. NOXA, PUMA) is dispensable for protection against cancers. Thus, the non-classical functions of p53 must be studied to better understand its tumor suppressive mechanisms. [ABSTRACT FROM AUTHOR]

Background: Breast cancer endocrine therapy research has become a crucial domain in oncology since hormone receptor-positive breast cancers have been increasingly recognized, and targeted therapeutic interventions have been advancing over the past few years. This bibliometric analysis attempts to shed light on the trends, dynamics, and knowledge hotspots that have shaped the landscape of breast cancer endocrine therapy research between 2003 and 2022. Methods: In this study, we comprehensively reviewed the scientific literature spanning the above-mentioned period, which included publications accessible through the database of the Web of Science (WOS) and the National Center for Biotechnology Information (NCBI). Next, a systematic and data-driven analysis supported by sophisticated software tools was conducted, such that the core themes, prolific authors, influential journals, prominent countries, and critical citation patterns in the relevant research field can be clarified. Results: A continuous and substantial expansion of breast cancer endocrine therapy research was revealed over the evaluated period. A total of 1,317 scholarly articles were examined. The results of the analysis suggested that research on endocrine therapy for breast cancer has laid a solid basis for the treatment of hormone receptor-positive breast cancer. From a geographical perspective, the US, the UK, and China emerged as the most active contributors, illustrating the global impact of this study. Furthermore, our analysis delineated prominent research topics that have dominated the discourse in the past two decades, including drug therapy, therapeutic efficacy, molecular biomarkers, and hormonal receptor interactions. Conclusion: This comprehensive bibliometric analysis provides a panoramic view of the ever-evolving landscape of breast cancer endocrine therapy research. The findings highlight the trajectory of past developments while signifying an avenue of vast opportunities for future investigations and therapeutic advancements. As the field continues to burgeon, this analysis will provide valuable guidance for to researchers toward pertinent knowledge hotspots and emerging trends, which can expedite the discoveries in the realm of breast cancer endocrine therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: The RB and p53 pathways are two major tumor suppressive pathways. Hence, in almost all cancers, both pathways are disabled. E2F transcription factor is under the control of the RB pathway and fulfills pivotal roles in tumor suppression by triggering the p53 pathway upon loss of RB function. Although this notion has been well established, emerging evidence indicates that each player of the E2F-RB-p53 pathway possesses novel functions and regulatory mechanisms. This review aims to introduce the expanding roles of the E2F-RB-p53 pathway in tumor suppression. The transcription factor E2F links the RB pathway to the p53 pathway upon loss of function of pRB, thereby playing a pivotal role in the suppression of tumorigenesis. E2F fulfills a major role in cell proliferation by controlling a variety of growth-associated genes. The activity of E2F is controlled by the tumor suppressor pRB, which binds to E2F and actively suppresses target gene expression, thereby restraining cell proliferation. Signaling pathways originating from growth stimulative and growth suppressive signals converge on pRB (the RB pathway) to regulate E2F activity. In most cancers, the function of pRB is compromised by oncogenic mutations, and E2F activity is enhanced, thereby facilitating cell proliferation to promote tumorigenesis. Upon such events, E2F activates the Arf tumor suppressor gene, leading to activation of the tumor suppressor p53 to protect cells from tumorigenesis. ARF inactivates MDM2, which facilitates degradation of p53 through proteasome by ubiquitination (the p53 pathway). P53 suppresses tumorigenesis by inducing cellular senescence or apoptosis. Hence, in almost all cancers, the p53 pathway is also disabled. Here we will introduce the canonical functions of the RB-E2F-p53 pathway first and then the non-classical functions of each component, which may be relevant to cancer biology. [ABSTRACT FROM AUTHOR]

Kombucha tea (KT) is a traditional non-alcoholic beverage, which is produced from the fermentation of black or green tea with a combination of acetic acid bacteria (AAB) and yeast. In addition to its historical usage in traditional medicine for various ailments, recent studies have demonstrated its potential as anti-cancer and anti-viral agent. Therefore, the objective of this study was to investigate the impact of KT on inducing anti-cancer effects in HepG-2 cells and its potential to exhibit anti-viral activity using Vero cells. MTT assay was conducted to assess the cytotoxicity of the KT and choose the optimal concentration for the study. Three types of cells: Normal human liver cells, HepG-2 cells, and Vero cells treated with KT doses of 10, 25, 50, 100, and 200 mg/ml. The IC50 concentration recorded was 54.87 mg/ ml for HEPG-2 tumor cell line and 73.8 mg/ ml for Vero cells. It was demonstrated that the KT had a strong cytotoxic effect on tumor cells as well as an antiproliferative function. However, it exhibited no discernible growth inhibition on normal cell lines. Flow cytometry was employed to study the KT's impact on inducing apoptosis (cell death), by exposing the cells to the KT for different periods (24, 48, 72 hours). It was found that KT has the ability to kill cancer-infected cells compared to the control, in early and late apoptosis of 11.27% and 11.01% respectively. The upregulation of the Bax and P53 genes and the downregulation of the Bcl-2 genes were part of the apoptotic process brought on by KT. These results showed that KT had an antiproliferative effect on HepG-2 cells through apoptosis-mediated cytotoxicity and cell cycle blockage at the G2/M phase. Regarding KT antiviral activity, it had a variable activity against different virus models. The percentage of depletion rate compared to its original viral titer recording was 23.1 %, 9.3% and 8.3% for Hepatitis A virus (HAV), rift valley fever virus (RVFV) and Herpes simplex virus (HSV), respectively. These findings imply that KT might be a good natural product therapy for anti-virus and anti-cancer medicines. [ABSTRACT FROM AUTHOR]

In this study, we introduced a simple method for detecting nucleoside triphosphates (NTPs) using controlled transcription-driven light-up aptamer amplification. Based on the concentration of target NTP, the light-up aptamer was amplified using a DNA template encoding the Broccoli aptamer sequence through an incomplete transcription mixture (without each NTP). The Broccoli aptamer associated with DFHBI-1T produced significantly enhanced fluorescence signals that could sensitively detect NTPs in a label-free manner. In addition, the proposed assay was useful for quantitatively detecting NTPs in serum. Thus, we expect that this method has great potential for NTP analysis in bioassays and biological researches. [ABSTRACT FROM AUTHOR]

Isolated limb perfusion (ILP) involves the local administration of high doses of anticancer drugs into a limb affected by unresectable locally advanced tumors (with special regard to in-transit melanoma metastases), minimizing systemic side effects. Tumor response to anticancer drugs may depend on the expression of apoptosis-related genes, such as SURVIVIN and MDM2. This retrospective cohort study investigated the association between tumor SURVIVIN and MDM2 expression levels and treatment response or clinical outcomes in patients undergoing ILP for in-transit melanoma metastases. The study cohort consisted of 62 patients with in-transit metastases who underwent ILP with tumor necrosis factor (TNF) and melphalan. Tissue samples were taken from the in-transit metastases, and RNA was extracted for gene expression analysis. Patients' response to treatment was assessed using clinical and radiological criteria two months after ILP, and disease response was classified as complete, partial, or stable/progressive disease. Disease-free survival (DFS) and overall survival (OS) were also analyzed. Expression of SURVIVIN and/or MDM2 was observed in 48% of patients; in these cases, complete response to ILP occurred in 40% of cases, with the overall response rate (complete + partial) being 85%. Patients with expression of MDM2 alone had a lower complete response rate (28%), while patients with expression of SURVIVIN alone had a higher complete response rate (50%). The combined expression of MDM2 and SURVIVIN resulted in a complete response rate of 30%. Patients without expression (of SURVIVIN or MDM2) had the highest complete response rate (58%). Survival analysis showed that high MDM2 expression was independently associated with a lower probability of a complete response to ILP. In addition, patients with MDM2 expression were three times more likely to have an incomplete response to ILP. This study highlights the importance of considering SURVIVIN and MDM2 expression in patients undergoing ILP for in-transit cutaneous melanoma metastases. High MDM2 expression was found to be an independent factor associated with a reduced likelihood of achieving a complete response to ILP, suggesting potential mechanisms of chemoresistance. These data support further research to explore the role of already available targeted therapies (i.e., MDM2 inhibitors) in improving tumor response to ILP in patients with in-transit melanoma metastases. [ABSTRACT FROM AUTHOR]

HfO2 shows promise for emerging ferroelectric and resistive switching (RS) memory devices owing to its excellent electrical properties and compatibility with complementary metal oxide semiconductor technology based on mature fabrication processes such as atomic layer deposition. Oxygen vacancy (Vo), which is the most frequently observed intrinsic defect in HfO2-based films, determines the physical/electrical properties and device performance. Vo influences the polymorphism and the resulting ferroelectric properties of HfO2. Moreover, the switching speed and endurance of ferroelectric memories are strongly correlated to the Vo concentration and redistribution. They also strongly influence the device-to-device and cycle-to-cycle variability of integrated circuits based on ferroelectric memories. The concentration, migration, and agglomeration of Vo form the main mechanism behind the RS behavior observed in HfO2, suggesting that the device performance and reliability in terms of the operating voltage, switching speed, on/off ratio, analog conductance modulation, endurance, and retention are sensitive to Vo. Therefore, the mechanism of Vo formation and its effects on the chemical, physical, and electrical properties in ferroelectric and RS HfO2 should be understood. This study comprehensively reviews the literature on Vo in HfO2 from the formation and influencing mechanism to material properties and device performance. This review contributes to the synergetic advances of current knowledge and technology in emerging HfO2-based semiconductor devices. [ABSTRACT FROM AUTHOR]

Cancer is one of the leading causes of death worldwide. Serious side effects, drug resistance and a narrow therapeutic window of chemotherapy drugs have led to the exploration and discovery of new natural anticancer agents. Alvaradoins are the secondary metabolites of the Alvaradoa Liebm. plant species, from the Picramniaceae family, belonging to the class of anthracenone C-glycosides. Among them, alvaradoin E, isolated from A. haitiensis Urb., is characterized by the most powerful anticancer properties as demonstrated by in-vitro and in-vivo assays. This updated review aims to provide new insights into the anticancer efficacy of alvaradoin E and analyses molecular pharmacological evidence to contribute to researchers' efforts to discover new adjunctive therapies in the pharmacotherapeutic management of cancer. To achieve this goal, relevant recent data on the anticancer pharmacological mechanisms of alvaradoin E were searched in specialized databases such as PubMed/ MedLine, Scopus, TRIP database, Web of Science, and Google Scholar. Most of the studies investigated the cytotoxic effects of alvaradoins and the extracts of the Alvaradoa species. Alvaradoin E excelled in its tumor-modulating activity in vitro in several human carcinomas (epidermoid, prostate, colon, lung), promyelocytic leukemia, and cells expressing telomerase reverse transcriptase. The cytotoxic effects of alvaradoin E were associated with its capacity to induce cell apoptosis. Further detailed studies are necessary to explain the precise mechanisms of actions, the effects on living organisms and possible adverse effects. Although data on its anticancer activity in vivo are scarce, Alvaradoin E can develop into a promising agent in fighting carcinoma. [ABSTRACT FROM AUTHOR]

Simple Summary: This comprehensive review focuses on the role of epigenetics in oral squamous cell carcinoma (OSCC), a prevalent type of oral cancer. The review highlights the importance of epigenetic changes, including DNA methylation, histone modifications, and miRNAs, in OSCC development and progression. Aberrant DNA methylation of tumor suppressor genes (TSGs) promotes tumor growth, making gene methylation patterns potential biomarkers for OSCC detection. Histone modifications, such as acetylation, methylation, phosphorylation, and ubiquitination, impact gene expression by modifying chromatin structure. Dysregulated miRNAs also contribute to OSCC progression. Epigenetic-targeted therapies, such as DNMT and HDAC inhibitors, show promise in modifying abnormal gene expression patterns, potentially leading to improved treatment outcomes for OSCC. However, challenges remain in biomarker identification and developing effective combination treatments. Understanding and targeting these epigenetic processes offer potential strategies to overcome drug resistance and improve OSCC treatment efficacy. Overall, the review highlights the potential of understanding and targeting epigenetic processes to overcome challenges and improve the efficacy of OSCC treatment, offering valuable insights for society in the diagnosis and treatment of oral cancer. Oral squamous cell carcinoma (OSCC) is a prevalent and significant type of oral cancer that has far-reaching health implications worldwide. Epigenetics, a field focused on studying heritable changes in gene expression without modifying DNA sequence, plays a pivotal role in OSCC. Epigenetic changes, encompassing DNA methylation, histone modifications, and miRNAs, exert control over gene activity and cellular characteristics. In OSCC, aberrant DNA methylation of tumor suppressor genes (TSG) leads to their inactivation, subsequently facilitating tumor growth. As a result, distinct patterns of gene methylation hold promise as valuable biomarkers for the detection of OSCC. Oral cancer treatment typically involves surgery, radiation therapy, and chemotherapy, but even with these treatments, cancer cells cannot be effectively targeted and destroyed. Researchers are therefore exploring new methods to target and eliminate cancer cells. One promising approach is the use of epigenetic modifiers, such as DNA methyltransferase (DNMT) inhibitors and histone deacetylase (HDAC) inhibitors, which have been shown to modify abnormal epigenetic patterns in OSCC cells, leading to the reactivation of TSGs and the suppression of oncogenes. As a result, epigenetic-targeted therapies have the potential to directly alter gene expression and minimize side effects. Several studies have explored the efficacy of such therapies in the treatment of OSCC. Although studies have investigated the efficacy of epigenetic therapies, challenges in identifying reliable biomarkers and developing effective combination treatments are acknowledged. Of note, epigenetic mechanisms play a significant role in drug resistance in OSCC and other cancers. Aberrant DNA methylation can silence tumor suppressor genes, while alterations in histone modifications and chromatin remodeling affect gene expression related to drug metabolism and cell survival. Thus, understanding and targeting these epigenetic processes offer potential strategies to overcome drug resistance and improve the efficacy of cancer treatments in OSCC. This comprehensive review focuses on the complex interplay between epigenetic alterations and OSCC cells. This will involve a deep dive into the mechanisms underlying epigenetic modifications and their impact on OSCC, including its initiation, progression, and metastasis. Furthermore, this review will present the role of epigenetics in the treatment and diagnosis of OSCC. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-refractory lung adenocarcinoma (LUAD) progression is a major clinical problem. New approaches to predict and prevent acquired resistance to EGFR TKIs are urgently needed. Here, we show that dopamine and cyclic AMP-regulated phosphoprotein, Mr 32000 (DARPP-32) physically recruits ERBB3 (HER3) to EGFR to mediate switching from EGFR homodimers to EGFR:ERBB3 heterodimers to bypass EGFR TKI-mediated inhibition by potentiating ERBB3-dependent activation of oncogenic signaling. In paired LUAD patient-derived specimens before and after EGFR TKI-refractory disease progression, we reveal that DARPP-32 and kinase-activated EGFR and ERBB3 proteins are overexpressed upon acquired resistance. In mice, DARPP-32 ablation sensitizes gefitinib-resistant xenografts to EGFR TKIs, while DARPP-32 overexpression increases gefitinib-refractory LUAD progression in gefitinib-sensitive lung tumors. We introduce a DARPP-32-mediated, ERBB3-dependent mechanism the LUAD cells use to evade EGFR TKI-induced cell death, potentially paving the way for the development of therapies to better combat therapy-refractory LUAD progression., (© 2021. The Author(s).)

Background: Breast cancer is the most common cancer affecting women across the world. Tumor endothelial cells (TECs) and malignant cells are the major constituents of the tumor microenvironment (TME), but their origin and role in shaping disease initiation, progression, and treatment responses remain unclear due to significant heterogeneity. Methods: Tissue samples were collected from eight patients presenting with breast cancer. Single-cell RNA sequencing (scRNA-seq) analysis was employed to investigate the presence of distinct cell subsets in the tumor microenvironment. InferCNV was used to identify cancer cells. Pseudotime trajectory analysis revealed the dynamic process of breast cancer angiogenesis. We validated the function of small extracellular vesicles (sEVs)-derived protein phosphatase 1 regulatory inhibitor subunit 1B (PPP1R1B) in vitro experiments. Results: We performed single-cell transcriptomics analysis of the factors associated with breast cancer angiogenesis and identified twelve subclusters of endothelial cells involved in the tumor microenvironment. We also identified the role of TECs in tumor angiogenesis and confirmed their participation in different stages of angiogenesis, including communication with other cell types via sEVs. Overall, the research uncovered the TECs heterogeneity and the expression levels of genes at different stages of tumor angiogenesis. Conclusions: This study showed sEVs derived from breast cancer malignant cells promote blood vessel formation by activating endothelial cells through the transfer of PPP1R1B. This provides a new direction for the development of anti-angiogenic therapies for human breast cancer. [ABSTRACT FROM AUTHOR]

MDM2 is an E3 ubiquitin ligase which is crucial for the degradation and inhibition of the key tumor-suppressor protein p53. In this work, we explored the stability and the conformational features of the N-terminal region of MDM2 (N-MDM2), through which it binds to the p53 protein as well as other protein partners. The isolated domain possessed a native-like conformational stability in a narrow pH range (7.0 to 10.0), as shown by intrinsic and 8-anilinonapthalene-1-sulfonic acid (ANS) fluorescence, far-UV circular dichroism (CD), and size exclusion chromatography (SEC). Guanidinium chloride (GdmCl) denaturation followed by intrinsic and ANS fluorescence, far-UV CD and SEC at physiological pH, and differential scanning calorimetry (DSC) and thermo-fluorescence experiments showed that (i) the conformational stability of isolated N-MDM2 was very low; and (ii) unfolding occurred through the presence of several intermediates. The presence of a hierarchy in the unfolding intermediates was also evidenced through DSC and by simulating the unfolding process with the help of computational techniques based on constraint network analysis (CNA). We propose that the low stability of this protein is related to its inherent flexibility and its ability to interact with several molecular partners through different routes. [ABSTRACT FROM AUTHOR]

In this study, a sol-gel film based on lead sulfide (PbS) quantum dots incorporated into a host network was synthesized as a special nanostructured composite material with potential applications in temperature sensor systems. This work dealt with the optical, structural, and morphological properties of a representative PbS quantum dot (QD)-containing thin film belonging to the Al2O3–SiO2–P2O5 system. The film was prepared using the sol-gel method combined with the spin coating technique, starting from a precursor solution containing a suspension of PbS QDs in toluene with a narrow size distribution and coated on a glass substrate in a multilayer process, followed by annealing of each deposited layer. The size (approximately 10 nm) of the lead sulfide nanocrystallites was validated by XRD and by the quantum confinement effect based on the band gap value and by TEM results. The photoluminescence peak of 1505 nm was very close to that of the precursor PbS QD solution, which demonstrated that the synthesis route of the film preserved the optical emission characteristic of the PbS QDs. The photoluminescence of the lead sulfide QD-containing film in the near infrared domain demonstrates that this material is a promising candidate for future sensing applications in temperature monitoring. [ABSTRACT FROM AUTHOR]

Cancer is a complex and multifaceted disease with a high global incidence and mortality rate. Although cancer therapy has evolved significantly over the years, numerous challenges persist on the path to effectively combating this multifaceted disease. Natural compounds derived from plants, fungi, or marine organisms have garnered considerable attention as potential therapeutic agents in the field of cancer research. Ellagic acid (EA), a natural polyphenolic compound found in various fruits and nuts, has emerged as a potential cancer prevention and treatment agent. This review summarizes the experimental evidence supporting the role of EA in targeting key hallmarks of cancer, including proliferation, angiogenesis, apoptosis evasion, immune evasion, inflammation, genomic instability, and more. We discuss the molecular mechanisms by which EA modulates signaling pathways and molecular targets involved in these cancer hallmarks, based on in vitro and in vivo studies. The multifaceted actions of EA make it a promising candidate for cancer prevention and therapy. Understanding its impact on cancer biology can pave the way for developing novel strategies to combat this complex disease. [ABSTRACT FROM AUTHOR]

Zinc finger protein 500 (ZNF500) has an unknown expression pattern and biological function in human tissues. Our study revealed that the ZNF500 mRNA and protein levels were higher in breast cancer tissues than those in their normal counterparts. However, ZNF500 expression was negatively correlated with advanced TNM stage (p = 0.018), positive lymph node metastasis (p = 0.014), and a poor prognosis (p < 0.001). ZNF500 overexpression abolished in vivo and in vitro breast cancer cell proliferation by activating the p53‐p21‐E2F4 signaling axis and directly interacting with p53 via its C2H2 domain. This may prevent ubiquitination of p53 in a manner that is competitive to MDM2, thus stabilizing p53. When ZNF500‐∆C2H2 was overexpressed, the suppressed proliferation of breast cancer cells was neutralized in vitro and in vivo. In human breast cancer tissues, ZNF500 expression was positively correlated with p53 (p = 0.022) and E2F4 (p = 0.004) expression. ZNF500 expression was significantly lower in patients with Miller/Payne Grade 1–2 than in those with Miller/Payne Grade 3–5 (p = 0.012). ZNF500 suppresses breast cancer cell proliferation and sensitizes cells to chemotherapy. [ABSTRACT FROM AUTHOR]

Infrared solar cells are more effective than normal bandgap solar cells at reducing the spectral loss in the near-infrared region, thus also at broadening the absorption spectra and improving power conversion efficiency. PbS colloidal quantum dots (QDs) with tunable bandgap are ideal infrared photovoltaic materials. However, QD solar cell production suffers from small-areabased spin-coating fabrication methods and unstable QD ink. Herein, the QD ink stability mechanism was fully investigated according to Lewis acid-base theory and colloid stability theory. We further studied a mixed solvent system using dimethylformamide and butylamine, compatible with the scalable manufacture of method-blade coating. Based on the ink system, 100 cm² of uniform and dense near-infrared PbS QDs (~ 0.96 eV) film was successfully prepared by blade coating. The average efficiencies of above absorber-based devices reached 11.14% under AM1.5G illumination, and the 800 nm-filtered efficiency achieved 4.28%. Both were the top values among blade coating method based devices. The newly developed ink showed excellent stability, and the device performance based on the ink stored for 7 h was similar to that of fresh ink. The matched solvent system for stable PbS QD ink represents a crucial step toward large area blade coating photoelectric devices. [ABSTRACT FROM AUTHOR]

Simple Summary: Osteosarcoma is an aggressive cancer of the bone that can present in children or adults. It has historically been thought that adults have worse clinical outcomes than children. However, current treatment strategies for adults are largely extrapolated from pediatric studies since the majority of clinical trials for osteosarcoma treatments are based on younger patient populations. We summarize the current understanding of the molecular etiology of osteosarcoma and how it may differ between age groups, hypothesizing why adult patients have worse outcomes compared to children. Malignant bone tumors are commonly classified as pediatric or adolescent malignancies, and clinical trials for these diseases have generally focused on these populations. Of primary bone cancers, osteosarcoma is among the most common. Osteosarcoma has a bimodal age distribution, with the first peak occurring in patients from 10 to 14 years old, and the second peak occurring in patients older than 65, with about 25% of cases occurring in adults between 20 and 59 years old. Notably, adult osteosarcoma patients have worse outcomes than their pediatric counterparts. It remains unclear whether age itself is a poor prognostic factor, or if inherent differences in tumor biology exist between age groups. Despite these unknowns, current treatment strategies for adults are largely extrapolated from pediatric studies since the majority of clinical trials for osteosarcoma treatments are based on younger patient populations. In light of the different prognoses observed in pediatric and adult osteosarcoma, we summarize the current understanding of the molecular etiology of osteosarcoma and how it may differ between age groups, hypothesizing why adult patients have worse outcomes compared to children. [ABSTRACT FROM AUTHOR]

Primary lung carcinoma or lung cancer (LC) is classified into small-cell or non- small-cell (NSCLC) lung carcinoma. Lung squamous cell carcinoma (LSCC) is the second most common subtype of NSCLC responsible for 30% of all LCs, and its survival remains low with only 24% of patients living for five years or longer post- diagnosis primarily due to the advanced stage of tumors at the time of diagnosis. The pathogenesis of LSCC is still poorly understood and has hampered the development of effective diagnostics and therapies. This review highlights the known risk factors, genetic and epigenetic alterations, miRNA biomarkers linked to the development and diagnosis of LSCC and the lack of therapeutic strategies to target specifically LSCC. We will also discuss existing animal models of LSCC including carcinogen induced, transgenic and xenograft mouse models, and their advantages and limitations along with the chemopreventive studies and molecular studies conducted using them. The importance of developing new and improved mouse models will also be discussed that will provide further insights into the initiation and progression of LSCC, and enable the identification of new biomarkers and therapeutic targets. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most common malignancy, and conventional medicine has failed to establish efficient treatment modalities. Conventional medicine failed due to lack of knowledge of the mechanisms that underpin the onset and metastasis of tumors, as well as resistance to treatment regimen. However, Complementary and Alternative medicine (CAM) modalities are currently drawing the attention of both the public and health professionals. Our study examined the effect of a super-combination (SC) of crude extracts, which were isolated from three selected Qatari medicinal plants, on the proliferation, motility and death of BC cells. Our results revealed that SC attenuated cell growth and caused the cell death of MDA-MB-231 cancer cells when compared to human normal neonatal fibroblast cells. On the other hand, functional assays showed that SC reduced BC cell migration and invasion, respectively. SC-inhibited cell cycle and SC-regulated apoptosis was most likely mediated by p53/p21 pathway and p53-regulated Bax/BCL-2/Caspace-3 pathway. Our ongoing experiments aim to validate these in vitro findings in vivo using a BC-Xenograft mouse model. These findings support our hypothesis that SC inhibited BC cell proliferation and induced apoptosis. These findings lay the foundation for further experiments, aiming to validate SC as an effective chemoprevention and/or chemotherapeutic strategy that can ultimately pave the way towards translational research/clinical trials for the eradication of BC. [ABSTRACT FROM AUTHOR]

Breast cancer is the frequently diagnosed cancer and the leading cancer death among women. The growing tumour of the breast is composed of both normoxic and hypoxic cells, and the heterogeneity of tumour affects the targeted treatment strategies against breast cancer. The functional and therapeutic status of the Warburg effect is mostly recognized, and the genes involved in glycolysis have become a target for anticancer therapeutic strategies. Glut-1 is essential for basal glucose uptake among the glucose transporters and could act as a potential target for anticancer therapy. In the present study, we explored the alteration in the metabolic phenotype of SKBR-3 cells, representing HER-2 overexpressed breast cancer cell line, with Glut-1 inhibition by a synthetic small molecule inhibitor WZB117 in the presence or absence of cobalt chloride (CoCl2) induced biochemical hypoxia in vitro. We found that WZB117 and CoCl2 in combination could inhibit metabolic phenotype characteristics such as glucose uptake, cell migration, lactate and ATP production in SKBR-3 cells. Also, Glut-1 inhibition induced apoptosis and cell cycle arrest at the G0–G1 phase even under CoCl2-induced mimic hypoxia. Our findings suggest that Glut-1 inhibition by WZB117 could overcome the protective effect of CoCl2 mimic hypoxia by regulating glycolysis and altering the metabolic phenotype of breast cancer cells. The considering excellent efficacy and minimal toxicity suggest that WZB117 may be a promising anticancer drug to the current therapies. [ABSTRACT FROM AUTHOR]

Raman scattering spectra of 1–2 μm thick n-PbS(111) epitaxial films grown by molecular beam epitaxy on BaF2(111) substrates were obtained and analyzed. The spectra were recorded at a low excitation level of 0.36 mW/μm2, which did not cause photo- and thermal degradation of the films. It is shown that, in accordance with the symmetry selection rules, the bands in the spectra correspond to overtone or combination tones of phonon modes of PbS at special points of the Brillouin zone. The analysis of the bands of oxides and oxysulfates of lead, which can mask the bands of lead sulfide, was carried out. The obtained data were used in the analysis of the recorded Raman scattering spectra by epitaxial films of a ternary solid solution PbS0.5Se0.5. [ABSTRACT FROM AUTHOR]

In the current context, there is a great desire to develop renewable energy sources as a power source. In order to improve the power conversion efficiency (PCE) of silicon solar cells, several studies are being undertaken in this area. This investigation focuses on preparing ZnO-Al2O3 blend as an antireflective coating (ARC) for improving the efficiency of polycrystalline silicon power conversion. The sol—gel method was employed to synthesis ZnO-Al2O3 blend which is produced by mixing zinc oxide with aluminium oxide. The spin coating process was used to deposit single to four layers of ZnO-Al2O3 blend on a silicon solar substrate. The thickness of ZnO-Al2O3coating obtained was measured with the help of atomic force microscopy (i.e.40 nm).The effect of zinc oxide and aluminium oxide coating on electrical, structural and optical characteristics of coated polycrystalline silicon solar cells, as well as cell temperature is investigated. A layer deposition of a single to multiple layers on a silicon solar cell was identified by an increase in layer thickness. At a low cell temperature (40 °C), the triple layer(LIII)deposition attained a maximum absorbance of 92% and power conversion efficiency (PCE) of 18.8%, demonstrating that photons diffuse on the solar cells were increased. The results show that zinc oxide and aluminium oxide mixture is a good anti-reflection coating material in improving silicon solar cell power conversion efficiency. [ABSTRACT FROM AUTHOR]

The remarkable impact of RNA nanomedicine during the COVID-19 pandemic has demonstrated the expansive therapeutic potential of this field in diverse disease contexts. In recent years, RNA nanomedicine targeting the liver has been paradigm-shifting in the management of metabolic diseases such as hyperoxaluria and amyloidosis. RNA nanomedicine has significant potential in the management of liver diseases, where optimal management would benefit from targeted delivery, doses titrated to liver metabolism, and personalized therapy based on the specific site of interest. In this review, we discuss in-depth the different types of RNA and nanocarriers used for liver targeting along with their specific applications in metabolic dysfunction-associated steatotic liver disease, liver fibrosis, and liver cancers. We further highlight the strategies for cell-specific delivery and future perspectives in this field of research with the emergence of small activating RNA, circular RNA, and RNA base editing approaches., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Myositis ossificans, a benign tumor composed of spindle cells and osteoblasts, can clinically and radiologically mimic osteosarcoma. While recognition and accurate diagnosis of myositis ossificans can be a challenge, this is critical as it may allow a conservative surgical approach to maximize functional outcomes. Herein, we present a patient with surface myositis ossificans confirmed genetically by the presence of COL1A1::USP6 gene fusion, along with a literature review. Due to the enhanced visualization of the bone matrix, computed tomography (CT) imaging may be a superior imaging modality to magnetic resonance (MR) imaging. Staged biopsies with samples obtained from the periphery and center of the lesions may allow pathologists to discern the zonal distribution histologically. Furthermore, immunohistochemistry fluorescence in situ hybridization and molecular testing can aid in the distinction of myositis ossificans from mimics. Because of their resemblance to other bone tumors, these cases of myositis ossificans highlight the importance of a multidisciplinary approach integrating clinical, radiologic, and pathologic analysis and involving serial imaging, sampling, and judicious use of ancillary immunohistochemical and molecular testing., (© 2024 Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

Recent progresses in diagnostic and therapeutic methods have significantly improved prognosis in cancer patients. However, cancer is still considered as one of the main causes of human deaths in the world. Late diagnosis in advanced tumor stages can reduce the effectiveness of treatment methods and increase mortality rate of cancer patients. Therefore, investigating the molecular mechanisms of tumor progression can help to introduce the early diagnostic markers in these patients. MicroRNA (miRNAs) has an important role in regulation of pathophysiological cellular processes. Due to their high stability in body fluids, they are always used as the non-invasive markers in cancer patients. Since, miR-363 deregulation has been reported in a wide range of cancers, we discussed the role of miR-363 during tumor progression and metastasis. It has been reported that miR-363 has mainly a tumor suppressor function through the regulation of transcription factors, apoptosis, cell cycle, and structural proteins. MiR-363 also affected the tumor progression via regulation of various signaling pathways such as WNT, MAPK, TGF-β, NOTCH, and PI3K/AKT. Therefore, miR-363 can be introduced as a probable therapeutic target as well as a non-invasive diagnostic marker in cancer patients., (© 2024. The Author(s) under exclusive licence to University of Navarra.)

Ischemic stroke (IS) stands as a prominent cause of mortality and long-term disability around the world. It arises primarily from a disruption in cerebral blood flow, inflicting severe neural injuries. Hence, there is a pressing need to comprehensively understand the intricate mechanisms underlying IS and identify novel therapeutic targets. Recently, long noncoding RNAs (lncRNAs) have emerged as a novel class of regulatory molecules with the potential to attenuate pathogenic mechanisms following IS. Among these lncRNAs, MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) has been extensively studied due to its involvement in the pathophysiological processes of IS. In this review, we provide an in-depth analysis of the essential role of MALAT1 in the development and progression of both pathogenic and protective mechanisms following IS. These mechanisms include oxidative stress, neuroinflammation, cell death signaling, blood brain barrier dysfunction, and angiogenesis. Furthermore, we summarize the impact of MALAT1 on the susceptibility and severity of IS. This review highlights the potential risks associated with the therapeutic use of MALAT1 for IS, which are attributable to the stimulatory action of MALAT1 on ischemia/reperfusion injury. Ultimately, this review sheds light on the potential molecular mechanisms and associated signaling pathways underlying MALAT1 expression post-IS, with the aim of uncovering potential therapeutic targets., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Biomolecular condensates have been proposed to mediate cellular signaling transduction. However, the mechanism and functional consequences of signal condensates are not well understood. Here we report that LATS2, the core kinase of the Hippo pathway, responds to F-actin cytoskeleton reduction and forms condensates. The proline-rich motif (PRM) of LATS2 mediates its condensation. LATS2 partitions with the main components of the Hippo pathway to assemble a signalosome for LATS2 activation and for its stability by physically compartmentalizing from E3 ligase FBXL16 complex-dependent degradation, which in turn mediates yes-associated protein (YAP)-transcriptional coactivator with PDZ-binding motif (TAZ) recruitment and inactivation. This oncogenic FBXL16 complex blocks LATS2 condensation by binding to the PRM region to promote its degradation. Disruption of LATS2 condensation leads to tumor progression. Thus, our study uncovers that the signalosomes assembled by LATS2 condensation provide a compartmentalized and reversible platform for Hippo signaling transduction and protein stability, which have potential implications in cancer diagnosis and therapeutics., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Cannabis is the most used illicit substance for recreational purposes around the world. However, it has become increasingly common to witness the use of approved cannabis preparations for symptoms management in various diseases. The aim of this study was to investigate the effects of cannabis nano emulsion in the liver of Wistar rats, with different proportions of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). For this, a total of 40 male Wistar rats were distributed into 5 groups, as follows (n = 8 per group): Control: G1, Experimental group (G2): treated with cannabis nano emulsion (THC and CBD) at a dose of 2.5 mg/kg, Experimental group (G3): treated with cannabis nano emulsion (THC and CBD) at a dose of 5 mg/kg, Experimental group (G4): treated with cannabis nano emulsion (CBD) at a dose of 2.5 mg/kg; Experimental group (G5): treated with cannabis nano emulsion (CBD) at a dose of 5 mg/kg. Exposure to the nano emulsion was carried out for 21 days, once a day, orally (gavage). Our results showed that cannabis nano emulsions at higher doses (5 mg/kg), regardless of the composition, induced histopathologic changes in the liver (G3 and G5) in comparison with the control group. In line with that, placental glutathione S-transferase (GST-P) positive foci increased in both G3 and G5 (p < 0.05), as well as the immune expression of Ki-67, vascular endothelial growth factor (VEGF) and p53 (p < 0.05). Also, the nano emulsion intake induced an increase in the number of micronucleated hepatocytes in G5 (p < 0.05) whereas G3 showed an increase in binucleated cells (p < 0.05). As for metanuclear alterations, karyolysis and pyknosis had an increased frequency in G3 (p < 0.05). Taken together, the results show that intake of cannabis nano emulsion may induce degenerative changes and genotoxicity in the liver in higher doses, demonstrating a clear dose-response relationship., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)