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Cyclin-dependent kinases (CDKs) are crucial for controlling the cell cycle, and many malignancies are linked to CDK dysfunction. Therefore, CDKs are desirable targets for cancer treatment. Since abnormal expression of CDK4/6 is the etiology of glioblastoma, it is imperative to investigate the mechanism underlying CDK4/6 selectivity for inhibitors compared to CDK1/2, another member of the family. This study used a range of molecular docking and bioinformatics techniques to characterize the specific efficacy of ligands as inhibitors and their interaction with CDK6. Ligand-based virtual screening was performed using 6OQL’ligand. Using Maestro 12.5, ligands were docked to the interaction site of CDK6 with a reference co-crystallized ligand (CCL). The ligands were analyzed for absorption, distribution, metabolism, excretion, and toxicity (ADMET). Using density functional theory (DFT) analysis, the selected ligands were found to have substantial stability. One ligand, Mol_370, which closely resembles the characteristics of CCL, was simulated using molecular dynamics. The results revealed that amino acids and ligands interact at the CDK6 inhibitor-binding site via typical chemical interactions, such as hydrophobic interactions and hydrogen bonds, as demonstrated by the docking data. MD simulations revealed that Mol_ 370 is compatible with CCL, leading to changes in both structure and function. In conclusion, this study offers significant insights into the development and refinement of inhibitors that can successfully target CDK6 and produce novel cancer treatments.

Glioblastoma is the most prevalent type of brain tumor, and because of drug resistance, treatment for gliomas has been less successful. Citronellol is an acyclic monoterpene alcohol with various pharmacological properties. This study aimed to evaluate the effect of citronellol and its nanoformulation on glioblastoma cell proliferation. The physicochemical properties of citronellol and its synthesized silver nanoconjugates (CN@AgNPs) were evaluated using DFT and ADMET studies. The targets of the investigation (p53 and CDK4) were identified through the application of chemogenomics and analysis of the STRING protein-protein interaction network. Ligands were docked to the interaction sites of specific targets using AutoDock Vina 1.5.7. Molecular dynamics were used to mimic the citronellol complex CDK4 and p53. Because metallic bonds, which provide metals with unique strength and stability, are more resilient and long-lasting than hydrogen bonds, the results showed that the CN@AgNPs generated a more stable complex. Citronellol and CN@AgNPs were assessed by an in vitro study to determine the expression of IC 50 concentration for the top scored selected genes to confirm the cytotoxicity of the compound against the GBM cell line SF-767. The findings showed that Citronellol and CN@AgNPs had concentration-dependent cytotoxic effects. Citronellol and CN@AgNPs, with IC 50 values of 20.04 ± 4 µg/mL and 19.67 ± 4 µg/mL, respectively, decreased CDK4 expression and raised p53 expression in the SF-767 cancer cell line. In conclusion, the cytotoxicity and inhibition index of glioblastoma cells were increased by the phytocompounds coupled with AgNPs. Therefore, CN@AgNPs may be a good choice for treating cancer.

Breast cancer (BC) is the most common cancer and the leading cause of cancer-related deaths in Saudi Arabia. However, this malignancy can be tackled effectively with early detection, resulting in better patient outcomes and reduced mortality rates. Breast screening, whether self-screening or clinical screening, plays a pivotal role in early BC detection. Hence, understanding, knowledge, and perception of BC and its risk factors are very important in early BC diagnosis. The current study has been conducted to assess the understanding, knowledge, perception, and attitude of educated population of Asir region towards BC and its risk factors. The study was conducted among the participants aged 18 or above in various institutions of the Asir region in KSA using an online pre-validated questionnaire to assess the understanding, knowledge, and perception of BC and its risk factors. The study was completed by a total of 979 participants. The proportion of participants who demonstrated adequate knowledge and positive perception regarding the role of breast self-examination and early detection was greater than 50%, indicating an overall satisfactory level of breast cancer awareness among the study population. However, in identifying the risk factors of BC, < 50% of participants correctly identified the 8 correct risk factors out of 12. When analyzing the association of BC awareness with demographic characteristics, the results revealed that females had 2.012 times higher odds of BC awareness than males. Additionally, participants with higher education qualifications had 3.867 times higher odds of BC awareness than those with bachelor’s degrees. Also, the results show that demographic factors like female sex, age, marital status, urban residence, occupation (administrative staff), and higher education level were associated with the level of knowledge about breast cancer risk factors. Participants demonstrated generally good knowledge and perception of breast cancer, particularly regarding early detection and available screening tools. However, awareness of breast cancer risk factors was notably limited. Therefore, there is a clear need for targeted and region-specific awareness programs to enhance understanding and promote early intervention.

Naringenin (NAR), a flavanone abundant in citrus fruits, has shown antiproliferative effects in several cancers, including breast cancer. However, its precise molecular mechanisms remain unclear. This study integrates network pharmacology, molecular modeling, and in vitro assays to investigate the anti-breast cancer potential of NAR. Target Genes associated with both NAR and breast cancer were identified through multiple databases, yielding 62 overlapping genes, which were further analyzed via a protein–protein interaction (PPI) network. Gene Ontology (GO) and KEGG pathway enrichment analyses revealed key involvement of PI3K-Akt and MAPK signaling pathways in NAR’s mechanism of action. Molecular docking studies showed strong binding affinities of NAR with key targets SRC, PIK3CA, BCL2, and ESR1, findings supported by molecular dynamics (MD) simulations, which confirmed stable protein–ligand interactions. Cell-based assays using MCF-7 human breast cancer cells demonstrated that NAR inhibits proliferation, induces apoptosis, reduces migration, and increases reactive oxygen species (ROS) generation. These results validate computational predictions and suggest that SRC may be a primary target mediating NAR’s anticancer activity. Collectively, this study provides mechanistic insights into the anti-breast cancer action of NAR and supports its potential as a lead compound for the development of SRC-targeted breast cancer therapies.

The death rate from breast cancer (BC) has dropped due to early detection and sophisticated therapeutic options, yet drug resistance and relapse remain barriers to effective, systematic treatment. Multiple mechanisms underlying miRNAs appear crucial in practically every aspect of cancer progression, including carcinogenesis, metastasis, and drug resistance, as evidenced by the elucidation of drug resistance. Non-coding RNAs called microRNAs (miRNAs) attach to complementary messenger RNAs and degrade them to inhibit the expression and translation to proteins. Evidence suggests that miRNAs play a vital role in developing numerous diseases, including cancer. They affect genes critical for cellular differentiation, proliferation, apoptosis, and metabolism. Recently studies have demonstrated that miRNAs serve as valuable biomarkers for BC. The contrast in the expression of miRNAs in normal tissue cells and tumors suggest that miRNAs are involved in breast cancer. The important aspect behind cancer etiology is the deregulation of miRNAs that can specifically influence cellular physiology. The main objective of this review is to emphasize the role and therapeutic capacity of tumor suppressor miRNAs in BC and the advancement in the delivery system that can deliver miRNAs specifically to cancerous cells. Various approaches are used to deliver these miRNAs to the cancer cells with the help of carrier molecules, like nanoparticles, poly D, L-lactic-co-glycolic acid (PLGA) particles, PEI polymers, modified extracellular vesicles, dendrimers, and liposomes. Additionally, we discuss advanced strategies of TS miRNA delivery techniques such as viral delivery, self-assembled RNA-triple-helix hydrogel drug delivery systems, and hyaluronic acid/protamine sulfate inter-polyelectrolyte complexes. Subsequently, we discuss challenges and prospects on TS miRNA therapeutic delivery in BC management so that miRNAs will become a routine technique in developing individualized patient profiles.

Nanotechnology is a rapidly developing field of research that studies materials having dimensions of less than 100 nanometers. It is applicable in many areas of life sciences and medicine including skin care and personal hygiene, as these materials are the essential components of various cosmetics and sunscreens. The aim of the present study was to synthesize Zinc oxide (ZnO) and Titanium dioxide (TiO2) nanoparticles (NPs) by using Calotropis procera (C. procera) leaf extract. Green synthesized NPs were characterized by UV spectroscopy, Fourier transform infrared (FTIR), X-ray diffraction (XRD), and Scanning Electron Microscopy (SEM) to investigate their structure, size, and physical properties. The antibacterial and synergistic effects of ZnO and TiO2 NPs along with antibiotics were also observed against bacterial isolates. The antioxidant activity of synthesized NPs was analyzed by their α-diphenyl-β-picrylhydrazyl (DPPH) radical scavenging activity. In vivo toxic effects of the synthesized NPs were evaluated in albino mice at different doses (100, 200, and 300 mg/kg body weight) of ZnO and TiO2 NPs administered orally for 7, 14, and 21 days. The antibacterial results showed that the zone of inhibition (ZOI) was increased in a concentration-dependent manner. Among the bacterial strains, Staphylococcus aureus showed the highest ZOI, i.e., 17 and 14 mm against ZnO and TiO2 NPs, respectively, while Escherichia coli showed the lowest ZOI, i.e., 12 and 10 mm, respectively. Therefore, ZnO NPs are potent antibacterial agents compared to TiO2 NPs. Both NPs showed synergistic effects with antibiotics (ciprofloxacin and imipenem). Moreover, the DPPH activity showed that ZnO and TiO2 NPs have significantly (p > 0.05) higher antioxidant activity, i.e., 53% and 58.7%, respectively, which indicated that TiO2 has good antioxidant potential compared to ZnO NPs. However, the histological changes after exposure to different doses of ZnO and TiO2 NPs showed toxicity-related changes in the structure of the kidney compared to the control group. The current study provided valuable information about the antibacterial, antioxidant, and toxicity impacts of green synthesized ZnO and TiO2 NPs, which can be influential in the further study of their eco-toxicological effects.

Abstract Introduction: The present study was undertaken on cases of prostate carcinoma and we tried to determine the relationship of elevated prostate specific antigen (PSA) level to histopathologic features associated with cancer in prostate biopsies and their relation to newest grade groups. Materials and Methods: The study was conducted in a tertiary health care center over a span of 3 years on patients with prostatic adenocarcinoma. The hematoxylin and eosin sections were reviewed as per World Health Organization 2016 new grading system and various other associated histopathological findings in the tissue noted. We tried to analyse correlation between serum PSA levels and histopathological features. Results: The majority of patients were in the age group of 70–80. Many patients (9/44) had the PSA in the range of 20–40 ng/ml and 10 patients (22.7%) had 80–100 ng/ml. There were three patients with normal PSA level and six patients with borderline level. Nine of 10 patients with marked increase in PSA level had higher grade groups. Histological subtyping showed 42 cases of acinar adenocarcinoma and 2 cases of ductal carcinoma. A number of associated findings were seen like benign prostatic hyperplasia (BPH): 13 cases, prostatitis: 28 cases, prostatic intraepithelial neoplasia: 7 cases - Low grade (1 case) and high grade (6 cases), and atrophy: 9 cases. Conclusions: We noticed majority of patients with grade group (GG) 3 and above had PSA value of more than 40 ng/ml, but PSA of <40 ng/ml did not correlate with the histologic grade groups. There was significant cut off value of PSA level 20 ng/ml between GG2 and GG3, differentiation of which is of clinical and histopathological significance. Histological subtyping showed acinar adenocarcinoma has no significant correlation with PSA levels however ductal carcinoma was associated with PSA levels <20 ng/ml. BPH association was seen to have PSA level of <40 ng/ml in majority of cases. The intensity of inflammation did not correlate with either degree of PSA level or histologic GG. We concluded serum PSA assay has prognostic application in the evaluation of patients undergoing prostate biopsies.

The computed tomography (CT) of the abdomen with contrast revealed findings of irregular cecal wall thickening, ileocecal intussusception with matted bowel loops, and heterogeneous mass measuring 12 × 5 cm in right iliac fossa with subcentimeter lymphadenopathy. [3] Aggressive surgical resection has been the mainstay of treatment for most melanomas that have not disseminated at the time of diagnosis followed by postoperative radiation therapy, chemotherapy, and immunotherapy for any residual disease or nodal involvement. [...]primary melanoma of colon is a rare aggressive tumor, which needs to be differentiated from metastatic tumor with surgical resection being the main modality of treatment.

Blood cancer, also known as hematological malignancy, is one of the devastating types of cancer that has significantly paved its mortality mark globally. It persists as an extremely deadly cancer type and needs utmost attention owing to its negligible overall survival rate. Major challenges in the treatment of blood cancer include difficulties in early diagnosis, as well as severe side effects resulting from chemotherapy. In addition, immunotherapies and targeted therapies can be prohibitively expensive. Over the past two decades, scientists have devised a few nanoparticle-based drug delivery systems aimed at overcoming this challenge. These therapeutic strategies are engineered to augment the cellular uptake, pharmacokinetics, and effectiveness of anticancer drugs. However, there are still numerous types of nanoparticles that could potentially improve the efficacy of blood cancer treatment, while also reducing treatment costs and mitigating drug-related side effects. To the best of our knowledge, there has been limited reviews published on the use of nano-based drug delivery systems for the treatment of hematological malignancies. Therefore, we have made a concerted effort to provide a comprehensive review that draws upon recent literature and patents, with a focus on the most promising results regarding the use of nanoparticle-based approaches for the treatment of hematological malignancies. All these crucial points covered under a common title would significantly help researchers and scientists working in the area. Graphical Abstract

The aim of this study was to employ an agro-industrial byproduct, specifically Citrus sinensis peels, as a reservoir of polyphenols. The natural chemicals present in C. sinensis peels serve as reducing agents in an environmentally benign method for synthesizing silver nanoparticles (AgNPs). This methodology not only provides a more environmentally friendly method for synthesizing nanoparticles but also enhances the value of agricultural waste, emphasizing the sustainable utilization of resources. In our study, AgNPs were successfully synthesized using peel aqueous exact of C. sinensis and then their various biological activity has been investigated. The synthesized AgNPs were characterized by UV–vis spectroscopy, dynamic light scattering (DLS), scanning electron microscopy (SEM), energy-dispersive X-ray (EDX), and transmission electron microscopy (TEM) analysis. Furthermore, their effectiveness in inhibiting growth and biofilm formation of Escherichia coli, Staphylococcus aureus, and Candida albicans has been investigated. The minimum inhibitory concentrations (MIC) for E. coli and S. aureus were both 32 μg/mL, and for C. albicans, it was 128 µg/mL. At 250 µg/mL of AgNPs, 94% and 92% biofilm inhibition were observed against E. coli and S. aureus, respectively. Furthermore, AgNPs demonstrated significant toxic effects against human prostate cancer cell line DU145 as investigated by anti-apoptotic, 4′,6-diamidino-2-phenylindole (DAPI), reactive oxygen species (ROS), and acridine orange/ethidium bromide (AO/EtBr) assays. We also conducted uptake analysis on these pathogens and cancer cell lines to preliminarily investigate the mechanisms underlying their toxic effects. These findings confirm that AgNPs can serve as a cost-effective, non-toxic, and environmentally friendly resource for green synthesis of medicinal AgNPs. Moreover, this approach offers an alternative recycling strategy that contributes to the sustainable use of biological by-products.