Burn wounds present significant clinical challenges due to high infection risk, delayed healing, and extensive tissue damage. The development of biomimetic skin substitutes capable of simultaneously supporting tissue regeneration and preventing infection remains a critical need in burn wound management. In this study, a novel ceragenin (CSA-44)-loaded tri-layered skin substitute was developed to mimic the epidermis, dermis, and hypodermis and address both wound healing and infection prevention simultaneously. The substitute comprised a poly(ε-caprolactone) (PCL) film as the upper layer, polyvinyl alcohol (PVA)/sodium alginate (SA)-PCL nanofibers as the middle layer, and a CSA-44-loaded PVA/Gelatin (Gel) hydrogel as the bottom layer. The tri-layered scaffold exhibited a hierarchical porous architecture, high swelling capacity (557.75% ± 52.87%), controlled degradation behavior, and a water vapor transmission rate of 2514.92 ± 63.41 g/m2/day, indicating suitability for maintaining a moist wound environment. Drug release studies demonstrated controlled CSA-44 delivery, with 92.26% ± 6.90% cumulative release after 180 min. The scaffold exhibited strong antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA), with complete inhibition observed within minutes. Cytocompatibility studies using human keratinocyte (HaCaT) cells demonstrated that the ceragenin-loaded scaffold maintained acceptable cell viability within the tested concentration range. In addition, co-culture experiments with HaCaT and human umbilical vein endothelial (HUVEC) cells revealed enhanced endothelial tube formation, suggesting a favorable microenvironment for angiogenic signaling. The results suggested that the ceragenin-loaded tri-layered skin substitute holds promise as a multifunctional biomaterial for burn wound management by combining antimicrobial efficacy and tissue regeneration capability.

Thyroid cancer, the most common endocrine cancer worldwide, causes serious problems, particularly in women. Chalcones, derived from natural compounds and precursors of flavonoids, are known to hold promise in cancer treatment due to their anticarcinogenic effects in many types of cancer, including thyroid. In the current study, the anticarcinogenic effects of the synthesized 2-benzofuran-linked chalcone compound were investigated in human thyroid cancer cell lines (TPC-1 and 8505-C) and a healthy thyroid cell line (Nhty-Ori 3-1). The effects of the compound on cell viability in TPC-1 and 8505-C cells were examined using SRB assays at 24, 48, and 72 hours, and the SRB viability test findings were confirmed by ATP analysis at the end of the 48-hour treatment period. Triple fluorescent staining (Hoechst 33342 + Annexin-V + Propidium Iodide) was used to determine the cell death pathway responsible for the cytotoxic effects of the chalcone compound. Consequently, the cytotoxic effect of the chalcone compound was observed in TPC-1 and 8505-C cells, while the cytotoxic effect for Nhty-Ori 3-1 was found to be quite low. The triple staining revealed that the chalcone compound induced apoptosis in TPC- 1 and 8505-C cells. Based on these results, it was concluded that the anti-cancer mechanisms of the 2-benzofuran-linked chalcone compound in thyroid cancer should be investigated and further analyses should be conducted.

Background and Objectives: A subset of cancer patients treated with immune checkpoint inhibitors may experience rapid tumor progression rather than therapeutic benefit, a phenomenon described as hyperprogressive disease (HPD), which is linked to poor prognosis and shortened survival. Reliable biomarkers capable of predicting HPD remain lacking. To better understand the molecular background of HPD, we analyzed promoter region methylation and somatic mutation profiles in cancer-related genes in patients with malignant melanoma (MM) and renal cell carcinoma (RCC) undergoing anti-PD-1/PD-L1 treatment. Methods: Patients diagnosed with MM or RCC and treated with anti-PD-1/PD-L1 agents between 2011 and 2020 were included, and FFPE tumor samples along with paired normal tissues were analyzed. A diagnosis of HPD was assigned to patients with RECIST 1.1-defined progressive disease who demonstrated a ≥2-fold acceleration in tumor growth kinetics after initiation of immune checkpoint inhibitor therapy. Methylation-specific real-time PCR was performed on 54 samples (15 MM tumors, 22 RCC tumors, 17 RCC-matched adjacent normal samples) to assess promoter methylation of PIK3CA, BAP1, PTEN, and TP53. Next-generation sequencing (NGS) with an 86-gene pan-cancer panel was conducted on 9 HPD samples. Results: Promoter hypermethylation involving PIK3CA, BAP1, PTEN, and TP53 was more pronounced in HPD-associated tumor samples (n = 16) than in tumors without HPD (n = 21). Within the MM cohort, PTEN and TP53 methylation levels demonstrated statistically significant differences between the two groups (p = 0.005 and p = 0.028, respectively), while no comparable associations were observed in RCC patients. NGS analysis detected missense mutations classified as pathogenic or likely pathogenic in 5 of 9 HPD patients (55.6%), involving KIT, PTEN, and VHL. Conclusions: Promoter region hypermethylation in cancer-related genes may contribute to the aggressive tumor behavior observed in HPD. The somatic variants identified in HPD patients are consistent with known oncogenic pathways. These findings support further investigation of epigenetic and genomic biomarkers for HPD risk stratification in larger, prospective cohorts.

Background/aim: Diclofenac (Diclo), a widely used nonsteroidal antiinflammatory drug, has emerged as a potential candidate for drug repurposing in oncology, with reported anticancer effects extending beyond cyclooxygenase (COX) inhibition, including modulation of tumor metabolism. This study investigated the antiproliferative and glycolysis-associated effects of Diclo in MCF-7 breast cancer cells, alone and in combination with docetaxel (Doc) or 5-fluorouracil (5-FU). Materials and methods: Cell viability was assessed using the sulforhodamine B (SRB) assay. To evaluate metabolic alterations, glucose uptake and lactate release were quantified following treatment. In addition, Triosephosphate Isomerase (TPI) protein levels and Lactate Dehydrogenase (LDH) activity were measured to explore potential modulation of glycolytic pathways. Results: Diclo reduced MCF-7 viability in a dose-dependent manner (IC50: 78.37 μg/mL). Combining Diclo with Doc or 5-FU enhanced cytotoxicity compared with single agents. Although Diclo alone did not significantly change glucose uptake, Diclo+Doc and Diclo+5- FU significantly decreased glucose uptake, and lactate release was reduced, particularly in Diclo-containing treatments. Diclo decreased TPI levels, and Diclo-based combinations further reduced TPI. LDH activity decreased with Diclo, while certain combinations produced divergent LDH responses, suggesting treatment-dependent effects on lactate metabolism and/or cellular stress. Conclusion: Diclo potentiated the cytotoxic effects of Doc and 5-FU and was associated with reduced glycolytic readouts and decreased TPI in MCF-7 cells, supporting a potential role for Diclo as a metabolic modulator in breast cancer combination therapy.

Notwithstanding progress in chemotherapy, cancer recurrence resulting from metastasis continues to be a significant challenge. Consequently, targeting the epithelial–mesenchymal transition (EMT) has emerged as a viable approach to impede metastasis and enhance therapy success. In colorectal cancer, current initiatives focus on discovering new agents that are both efficacious and less harmful to normal cells. Plant-derived flavonoids and metal-based compounds exhibit significant medicinal potential. This research examined the anticancer efficacy of a Cu(II)-flavonoid complex comprising quercetin and 1,10-phenanthroline ligands in colorectal cancer cell lines HCT-116 and HT-29. The sulforhodamine B (SRB) assay assessed cell viability, yielding IC₅₀ values of 3.19 μM for HCT-116 and 1.81 μM for HT-29 after 48 h, but the individual ligands demonstrated no similar cytotoxicity. The compound exhibited lower cytotoxicity to normal colon cells (CCD-18Co) than toward colorectal cancer cells (HCT-116 and HT-29). Apoptosis induction was verified with Hoechst 33342, Annexin-V-FITC, and propidium Iodide staining, supplemented by M30-antigen ELISA, and further corroborated by the pan-caspase inhibitor Z-VAD-FMK and elevated levels of apoptotic protein markers such as cleaved caspase-8 and parp-1. Flow cytometry revealed G₀/G₁ phase arrest, indicating caspase-dependent apoptotic cell death. The compound also impeded epithelial-mesenchymal transition, as demonstrated by a dose-dependent reduction in migration and invasion in wound healing and Matrigel invasion experiments. Western blot analysis revealed elevated levels of E-cadherin and reduced levels of N-cadherin, vimentin, and snail. The Cu(II)-flavonoid combination demonstrates significant anti-proliferative, pro-apoptotic, and anti-metastatic properties in colorectal cancer cells, while exhibiting lower cytotoxic effects in normal colon cells. This underscores its potential as a viable candidate for additional molecular and in vivo assessment of the complex in colorectal cancer.

In this study, we investigated the anticancer effects of two synthesized 2-benzofuran-substituted chalcone derivatives (2a-2b) in combination with tamoxifen (TAM) on MCF-7 estrogen receptor-positive (ER+) breast cancer cells. Cytotoxicity was evaluated using the sulforhodamine B (SRB) assay in both MCF-7 and non-tumorigenic MCF-10 A cells. The combination index (CI) was calculated to determine synergistic interactions. Apoptotic cell death was confirmed via fluorescence microscopy using Annexin-V, Hoechst 33342, and Propidium Iodide (PI) staining. The involvement of apoptosis, necroptosis, and autophagy was further assessed using Z-VAD-FMK, Necrostatin-1 (Nec-1), Necrosulfonamide (NSA), and 3-Methyladenine (3-MA) inhibitors. Functional analyses including colony formation, migration, and Matrigel invasion assays were performed. Additionally, gene expression changes in apoptosis, necroptosis, and autophagy-related markers were quantified by qRT-PCR. The combination of 2-benzofuran-chalcone compounds with TAM exhibited a synergistic cytotoxic effect on MCF-7 cells, with significantly lower IC50 values compared to monotherapies, while exerting minimal toxicity on MCF10 A cells. Fluorescence staining revealed increased apoptotic features upon combination treatment. Inhibitor assays confirmed that the cell death mechanism was predominantly caspase-dependent apoptosis, with no significant involvement of necroptosis or autophagy. The combination treatment significantly impaired clonogenic capacity, cell migration, and Matrigel invasion. Gene expression analyses showed upregulation of pro-apoptotic markers and downregulation of anti-apoptotic markers, further validating apoptotic activation. This study demonstrates that 2-benzofuran-substituted chalcone derivatives synergize with TAM to induce apoptosis and suppress proliferative and metastatic potential in ER+ breast cancer cells. These findings reveal the potential of 2-benzofuran chalcone-tamoxifen combinations as a novel therapeutic strategy to enhance antitumor efficacy in hormone-dependent breast cancers.

Breast cancer is the most common malignancy among women worldwide. Despite the widespread use of various chemotherapy agents, the development of more effective and targeted treatment strategies is of critical importance. Tamoxifen, an estrogen receptor inhibitor, is widely used in the treatment of breast cancer; however, its resistance development and limiting effect create significant problems. Chalcone derivatives naturally found in plants are an important source of inspiration to enrich the repertoire of chemotherapeutics. Natural or synthetic derivatives of chalcones are being investigated in detail for their anticancer properties. In this study, it was aimed to evaluate the anticancer activity of a new treatment approach consisting of the combination of 2-benzofuran-linked chalcone complex and tamoxifen in MCF-7 breast cancer cells. The effects of 2-benzofuran-linked chalcone complex, tamoxifen and combination therapy on cell viability were determined by the SRB method. The determination of the death mode (apoptosis/necrosis) in cells was analyzed by the Annexin-V/Hoechst/Propidium Iodide triple staining method. In addition, colony formation abilities of the combination were tested.The results showed that the combination of 2-benzofuran-linked chalcone complex with tamoxifen increased cytotoxic activity and induced apoptosis in breast cancer cells in a dose- and time- dependent manner. It was also found that the colony formation capacity of the combination was inhibited. These results suggest that the combination of 2-benzofuran-linked chalcone complex and tamoxifen may be a promising and effective strategy in the treatment of breast cancer.

Cancer is one of the most important health problems of today, which ranks second in the list of known deaths. Leukemia remains one of the most important health problems of today, ranking second among known causes of cancer-related death. Although there are treatments that can be effective, new targets and drugs with high selectivity and efficacy are still needed, particularly for non-solid tumors such as leukemia. Many reported antileukemic agents suffer from poor selectivity and bioavailability. Pyrimidines, as fundamental components of DNA and RNA, have attracted significant attention in drug discovery and development. Among the pyrimidine family, Biginelli-derived tetrahydropyrimidines (THPMs) hold particular importance due to their broad pharmacological potential, including anticancer activity. In this study, THPM molecules, and their nanocomposites were synthesized and characterized by NMR, elemental analysis, DSC, TGA, FTIR, MS, and subsequently assessed for their in vitro anticancer activities. The cytotoxic effects were assessed in K-562, THP-1, and MOLT-4 leukemia cell lines using the MTT assay. Results demonstrated that selected THPM derivatives exhibited potent and selective cytotoxicity in distinct leukemia subtypes: compounds 4b, 4e, 4j, and 4k were most active in CML (K-562) cells: 4c, 4e, and 4g in AML (THP-1) cells; and 4b, 4g, 4j, and 4k in ALL (MOLT-4) cells. The observed selectivity is likely driven by phenotypic and genotypic differences among leukemia cell lines, underscoring the therapeutic potential of THPM scaffolds as targeted antileukemic agents. These findings provide a strong basis for further mechanistic studies and preclinical evaluation.

Molecularly imprinted polymer (MIP) nanoparticles offer a promising controlled drug delivery platform. In this study, amoxicillin (AMOX)-imprinted polymer nanoparticles (similar to 60 nm) were synthesized via emulsion polymerization and incorporated into polyvinyl alcohol (PVA)/sodium alginate (SA) [PVS] electrospun nanofibers to develop a novel wound dressing. The nanoparticle-embedded PVS nanofibers (PVS-AMOX-MIP) demonstrated a sustained cumulative drug release of 43.6% over 2 days, governed by non-Fickian transport per the Korsmeyer-Peppas kinetic model. The nanofibers exhibited favorable physical properties, including a high specific surface area (39.66 m(2)/g), optimal porosity (78.8%), and a water vapor transmission rate (1053.4 +/- 5.9 g/m(2)/day), ideal for wound healing. Antibacterial activity studies showed significant inhibition against Staphylococcus aureus and Escherichia coli, while biocompatibility assays confirmed the mat's noncytotoxic nature and ability to promote cell proliferation. Furthermore, angiogenesis studies revealed enhanced vascularization, which is critical for tissue regeneration. The developed strategy offers a unique approach for advanced wound care and controlled drug delivery applications by combining MIP nanoparticles' molecular recognition capability with the structural advantages of electrospun nanofibers.

Lung cancer is a type of cancer with high morbidity and mortality rates worldwide. The overall survival rate of lung cancer patients is low due to a lack of therapeutic options. Recently, the combination of histone deacetylase (HDAC) inhibitors with anti-cancer agents offers a promising therapeutic strategy for cancer treatment. Repurposing these drug combinations is important to evaluate their preventive effect on the epithelial mesenchymal transition (EMT) phenotype, which plays a critical role in tumor progression and metastasis. In this study, the changes that the combination of the HDAC inhibitor Valproic acid (VPA) and Wnt/β-Catenin pathway inhibitor Niclosamide (Niclo) may cause in cytotoxicity, apoptosis, cell cycle, and EMT mechanisms in lung cancer cell lines (A549 and H1299) were examined. According to the results, the combination of VPA + Niclo significantly reduced cell viability in lung cancer cells compared to the use of Niclo alone. ELISA and Western blot analyses revealed that the combination of VPA + Niclo significantly enhanced the total acetylation of Histone H3 compared to the use of VPA alone. It was also found that the combination treatment induced apoptosis by increasing the activity of Caspase 3/7 and Annexin-V and significantly increased the percentage of apoptotic cells by causing depolarization of mitochondria. After cell cycle analysis, the combination treatment increased G1 phase retention in A549 cells, while G1-G2/M phase retention increased in H1299 cells. Wound healing and transwell migration assay results showed that the VPA + Niclo combination treatment inhibited cell migration in lung cancer cells. According to Western blot and PCR results, after VPA + Niclo treatment, the increase in E-Cadherin levels and the decrease in β-Catenin, Fibronectin, Vimentin, and N-Cadherin levels at both protein and gene levels indicated that combination therapy may be useful in preventing the EMT process in lung cancer cells. As a result of the analyses, it was seen that VPA + Niclo combination therapy could play a critical role in preventing the acquisition of the mesenchymal phenotype, reducing cell migration and invasion ability, and preventing tumor cell survival and resistance to apoptosis. In conclusion, it was determined that VPA + Niclo combination treatment shows anticancer activity in lung cancer cells and is a promising approach that may have a synergistic effect in inhibiting EMT.

Cancer leads the list of causes of death worldwide, and the search for new and rapid treatment options for this disease has accelerated. New chemotherapeutic agents that inhibit tumor growth and proliferation are being introduced to the market; however, it presents various challenges, including the lengthy effectiveness of clinical trials, difficulty transitioning to phase 3 clinical stages, and high financial costs. A drug that had previously gained popularity in the market, has recently been repositioned for a different purpose, making it an excellent target for the treatment of several diseases. This review specifically focuses on the anti-cancer effects of repositioned antipsychotic medications that were studied for cancer treatment as well as their combination studies with other chemotherapeutic agents, using a literature search. A literature review covering the last 15 years was conducted using the PubMed (MEDLINE), Google Scholar, and Web of Science databases, with the keywords 'anticancer,' 'antipsychotic drugs,' and 'drug repurposing' used in combination. Studies that yielded productive results across broad historical ranges were included in the review. Initially, the correlation between schizophrenia patients and cancer was explored. Next, antipsychotic drugs with reported anticancer activities were identified, and their in vitro and in vivo anticancer mechanisms were revealed. Finally, the potential contributions and significance of these drugs in future therapeutic approaches were highlighted. In conclusion our literature search has revealed that antipsychotic medications can be useful in treating cancer.

BACKGROUND:Prostate cancer is a common and deadly cancer among men and has been the subject of many patients in its diagnosis and treatment. Imatinib, a tyrosine kinase inhibitor, can slow tumor formation by targeting c-KIT, an oncogenic receptor tyrosine kinase protein over-expressed in PCa cases. However, Imatinib has no effect on tr-KIT, a truncated form of c-KIT, which is over-expressed in PCa and is associated with neoplastic transformation. In this study, it is aimed to answer whether the anti-proliferative efficacy of Imatinib on PCa cells could be enhanced by inhibition of tr-KIT specific transcription factors. METHODS AND RESULTS:For this purpose, gene expression analysis and cell viability assays were performed in LNCaP prostate cancer cells to investigate the effects of inhibition of transcription factors controlling tr-KIT expression (YY1 and NFYA) in combination with Imatinib administration. As a result, YY1 and NFYA were identified as tr-KIT-specific transcription factors and found that their knockdown increased the effectiveness of Imatinib mesylate treatment on LNCaP cells. The study also analyzed the gene expression changes of c-KIT, FYN, PLCγ1, and SAM68 genes and found that SAM68 expression decreased with NFYA and YY1 knockdown, suggesting the existence of other unknown mediators in the tr-KIT pathway. CONCLUSIONS:All in all, this study demonstrates that tr-KIT may be a potential pharmacological target for prostate cancer treatment and that inhibition of the transcription factors YY1 and NFYA may enhance the efficacy of Imatinib. SAM68 was found to be the most affected protein by the treatments, guiding future research.

Prostate cancer is the second most commonly diagnosed cancer among men. Prostate cancer stem cells, which significantly impact patient survival, play a critical role in metastasis, recurrence, and therapy resistance. Alongside conventional treatments, interest has grown in the use of plant-derived chemotherapeutic agents and other natural products in prostate cancer. Chalcones, a subgroup of the flavonoid family, have gained attention due to their diverse biological properties and potential in anticancer drug development. This study aimed to investigate the cytotoxic and anti-metastatic effects of the 4-hydroxy-3-methoxyphenyl chalcone complex in a human prostate cancer cell line (PC-3) and a cancer stem cell-enriched subpopulation derived from it (PC-3s). Following characterization of PC-3s using cancer stem cell markers, the cytotoxic effects of the chalcone complex on PC-3, PC-3s, and healthy prostate stromal cells (WPMY-1) were assessed using Adenosine triphosphate (ATP) cell viability assays. The anti-metastatic potential of the chalcone complex was evaluated at the gene and protein levels using RT-PCR and Western blot analyses. Additionally, the effects of the complex on migration and colony-forming abilities of PC-3 cells were analyzed using scratch assay, colony formation assay, and transwell invasion assay. The chalcone complex significantly reduced cell viability in PC-3 and PC-3s compared to WPMY-1 cells. Notable changes were observed in the expression levels of EMT-related genes (WNT3a, FN1, VIM, CDH1, SANI1, CTNNB1, SOX-2, OCT- 4, NANOG) and proteins (E-Cadherin, Vimentin, Fibronectin, β-Catenin) following treatment. Furthermore, the chalcone complex suppressed migration, colony formation, and invasion capacities in PC-3 cells. The promising findings from this study suggest that the investigated chalcone complex may serve as an effective and potential new therapeutic molecule for prostate cancer. Its potential should be further validated through comprehensive in vitro and in vivo studies.

18 beta-Glycyrrhetinic acid (GA) is a pentacyclic triterpene which was obtained from the roots of Glycyrrhiza glabra known for its diverse pharmaceutical applications. The primary aim of this study is to enhance the pharmaceutical properties of GA by modifying it with a 1,2,3-triazole-functionalized ferrocene moiety. The hybrid compound 3 was synthesized by amide functionalization of GA at the C-30 position with ferrocene, linked via a 1,4-disubstituted 1,2,3-triazole bridge. Additionally, the C-3 hydroxyl group of GA was converted into an acetyl ester. The hybrid compound 3 was characterized using FT-IR, NMR (1H and 13C) and HR-MS. The aim of the modification was to enhance the cytotoxic and enzyme inhibitory effects of GA. 1,2,3,-Triazole substituted ferrocene (1), C-3 acetylated GA and the hybrid compound 3 were tested on A549, MCF-7, HCT-116, and PC-3 cancer cell lines. MCF-7 and HCT-116 cells showed the highest sensitivity to the compounds. Compound 3 showed more cytotoxicity than both GA and compound 1 with IC50 values of 23.97 and 50 mu M in MCF-7 and HCT-116 cells, respectively. Morphological analysis indicated that compound 3 induced apoptotic cell death. In addition, the inhibitory effect of compounds on carbonic anhydrase I-II isoenzymes (hCAI-II), acetylcholinesterase/butyrylcholinesterase (AChE/BChE) enzymes, and alpha-glucosidase was tested. According to the results, compound 3, exhibited the strongest inhibitory properties for all enzymes tested with IC50 values of 0.0323, 0.3058, 0.0078, 0.0090 and 0.0120 mu M, respectively. Molecular docking studies were performed to investigate the ligand-target protein interactions. Incorporating an organometallic sandwich-like compound ferrocene into GA via a 1,2,3-triazole bridge appears to be an effective strategy for modifying and enhancing its bioactivity.

Apoptosis is one of the fundamental mechanisms that prevents cancer development and has traditionally been regarded as irreversible once critical molecular events, such as caspase activation, have occurred. However, accumulating evidence has demonstrated that certain cells can survive even after entering advanced stages of apoptosis through a process known as anastasis. This phenomenon is thought to contribute to the development of therapeutic resistance and the emergence of more aggressive tumor phenotypes. Since cell fate decisions during and after anastasis are tightly regulated at the transcriptional level, and transcriptional control is largely governed by chromatin dynamics, investigating the associated epigenetic alterations provides critical insight into how these cells adapt and potentially acquire malignant traits. In this study, apoptosis was induced in non-small cell lung cancer cells using paclitaxel, and the surviving cells were subsequently re-cultured under drug-free conditions ed by a decrease. Western blot analyses revealed a significant increase in H3K9 and H3K27 levels, accompani in HDAC1 and HDAC2 expression (p < 0.05). qPCR results further confirmed these findings and demonstrated a statistically significant concordance with the Western blot data. These results suggest that anastasis is not merely an escape from cell death but also initiates an adaptive process involving epigenetic regulatory mechanisms. Overall, our findings highlight that targeting chromatin-modifying enzymes during anastasis may represent a promising therapeutic strategy to reduce the risk of recurrence and progression of post-apoptotic tumor cells.

Cancer is the second biggest cause of death after cardiovascular disorders and its incidence is rising significantly. One out of every ten cancer-related deaths is caused by colon cancer. The increasing incidence calls for creating focused therapeutic strategies with fewer adverse effects than traditional clinical techniques like radiation, chemotherapy, and immunotherapy. In this study, we evaluated the anticancer effects and mechanisms of a synthesized and characterized benzofuran ring-linked 3-nitrophenyl chalcone derivative, [1-(2-benzofuranyl)-3-(3-nitrophenyl)-2-propen-1-one], on colon cancer cells (HCT-116 and HT-29) as well as healthy colon cells (CCD-18Co). Cell viability analyses using the sulforhodamine B assay demonstrated that the IC₅₀ values after 48 h of treatment were 1.71 µM for HCT-116, 7.76 µM for HT-29, and higher than 10 µM for CCD-18Co cells. These results indicate a selective cytotoxic effect on cancer cells an essential criterion for evaluating anticancer compounds. Triple fluorescence staining, flow cytometry caspase 3/7 activity, along with protein expression analyses, confirmed that the compound induces apoptosis in both cancer cell lines. At IC₅₀ values, the derivative activated DR-4-mediated apoptosis at the membrane and BCL-2-mediated apoptosis intracellularly. Moreover, treatment with 12.5 µM of the compound for 24 h, corresponding to a cell cycle time, statistically significantly arrested the cell cycle at the G0/G1 phase. In addition, it inhibited cell migration and colony formation in a dose-dependent manner, starting from values as low as 1.56 µM. Additionally, the binding affinity of the derivative with target proteins was determined using artificial intelligence-assisted molecular modeling analysis. Collectively, these findings highlight the potential of this 3-nitrophenyl chalcone derivative as a promising candidate for the development of novel therapeutic agents against colon cancer.

Multiple myeloma (MM), a malignancy of plasma cells in the bone marrow, accounts for 1.8% of all cancers and about 10% of hematological malignancies. Although proteasome inhibitors such as bortezomib have significantly improved MM survival rates, resistance remains a major challenge, particularly in high-risk patients. One of the mechanisms contributing to this resistance is the activation of autophagy, allowing myeloma cells to survive proteotoxic stress induced by bortezomib. This study aimed to identify autophagy-related signaling pathways involved in bortezomib resistance using transcriptomic and network-based bioinformatics analyses. RNA-seq data (GSE144249) of bortezomib-resistant MM cells were analyzed for differentially expressed genes, followed by KEGG and GO enrichment analyses. Protein-protein interaction (PPI) networks were constructed to identify key hub genes potentially mediating autophagy-related resistance. Our results revealed the activation of autophagy pathways and highlighted specific candidate genes associated with bortezomib resistance. Further functional validation of these targets is warranted to support the development of novel therapeutic strategies against MM drug resistance.

Three new copper(II) complexes, [Cu(5-ClSal-Trp)(H2O)2] (1), [Cu(5-ClSal-Trp)(phen)] & sdot;C2H5OH (2) and [Cu (3,5-ClSal-Trp)(phen)] (3) (5-ClSal-Trp: Schiff base derived from 5-chlorosalicylaldehyde and L-tryptophan, 3,5-ClSal-Trp: Schiff base derived from 3,5-dichlorosalicylaldehyde and L-tryptophan, phen: 1,10-phenanthroline), have been synthesized and characterized by electronic absorption spectroscopy, CHN analysis, FTIR, ESI-MS and XRD techniques. Interaction of the complexes 1-3 with biomolecules {calf thymus DNA (CT-DNA) and bovine serum albumin (BSA)} has been investigated by electronic absorption and fluorescence spectroscopy. The results show that the complexes 1-3 can bind to CT-DNA via a moderate intercalation mode. Moreover, the fluorescence quenching mechanism between the complexes 1-3 and BSA is a static quenching process. Radical scavenging activity studies reveal that the complexes 1-3 show a moderate activity. Antiproliferative effects of the complexes 1-3 on both breast cancer cells (MCF-7 and MDA-MB-231) and healthy breast epithelial cells (MCF-10A) were also investigated using the Sulforhodamine B (SRB) viability assay. The results demonstrated that the complexes 1-3 exhibited a more pronounced cytotoxic effect on cancer cells compared to normal breast epithelial cells. Among the complexes, the best cytotoxic activity was obtained for the complex 3 against both human breast cancer cell lines. Further analysis indicated that the complex 3 induced apoptosis, as evidenced by fluorescent staining, positive Annexin-V-FITC staining, and the involvement of caspase. Subsequent to the administration of the complex 3, an evaluation of intracellular reactive oxygen species (ROS) generation was conducted through the utilization of dihydroethidium (DHE) fluorescent staining.

The field of corneal cell sheet engineering has evolved rapidly in the last decade; however, challenges related to transplantation into target tissue still exist, necessitating a new approach to integrate cell sheet technology onto a contact lens surface. In this study, a novel surface-modified contact lens was developed for corneal regenerative medicine to ensure the easy and safe integration of cell sheets into the target tissue. The lens surface was coated with a thermo-responsive polymer using the initiated chemical vapor deposition technique, facilitating the separation of tissue-integrated cell sheets from the coated lens surface by simply lowering the temperature. BEAS-2B and L929 cells, along with human limbal epithelial cells, were cultured on a crosslinked poly(2-(dimethylamino)ethyl methacrylate)-coated lens, providing temperature sensitivity for 14 days. At the end of the incubation period, the cultured cells were harvested as intact monolayer cell sheets through a simple temperature reduction, without enzymatic treatment or additional surgical procedures. Rapid and complete delamination of the cells planted and incubated on the coated lens surface was achieved at room temperature. Therapeutic contact lenses modified with cell sheet technology allowed targeted delivery of cells to the affected area of the cornea. Schematics depict the initated chemical vapor deposition of a temperature responsive polymer coating on contact lenses, enabling the temperature controlled detachment of limbal epithelial cells for cell sheet transplantation. image

Novel bioactive ternary nickel (II) complexes, [Ni(5BrSal-Phe)(phen)] (1) and [Ni(5BrSal-Tyr)(phen)] (2) (5BrSal-Tyr: Schiff base derived from 5-bromosalicylaldehyde and L-tyrosine, 5BrSal-Phe: Schiff base derived from 5-bromosalicylaldehyde and L-phenylalanine, phen: 1,10-phenanthroline), have been synthesized and characterized by electronic absorption spectroscopy, CHN, FTIR, ESI-MS and X-ray crystallography techniques. Interaction of the complexes with biomolecules (calf thymus DNA (CT-DNA) and bovine serum albumin (BSA)) has been investigated by electronic absorption and fluorescence spectroscopy. The results show that the complexes can bind to CT-DNA via a minor groove binding mode. Moreover, the fluorescence quenching mechanism between the complexes and BSA is a static quenching process. The antiproliferative activities of the complexes against breast cancer cells (MCF-7 and MDA-MB-231) and healthy breast epithelial cells (MCF-10A) were investigated. The complex 2 was found to have promising antiproliferative activity in selected cell line, with lower IC50 values than cisplatin. Molecular docking studies suggest that the complexes may serve as potential chemotherapeutic agents. These complexes have been observed to interact with various targets within cells, including the epidermal growth factor receptor (EGFR), bovine serum albumin (BSA), and B-DNA. Analyses indicate that these interactions are supported not only by conventional hydrogen bonds but also van der Waals forces and pi-pi interactions. Additionally, determining binding constants and regions enhances our understanding of how the complexes interact with target molecules. The results emphasize the importance of the complexes in cancer therapy by highlighting the necessity of understanding their molecular-level interactions with targets.