Nanoparticles synthesized from natural sources are gaining prominence for their unique physicochemical properties and biocompatibility. This study investigates the potential of wild mushrooms, specifically Chlorophyllum molybdites (Lepiota morganii, green-spored parasol), for the green synthesis of manganese oxide nanoparticles. Mycosynthesized nanoparticles (NPs) were characterized via spectroscopic techniques such as XRD, UV spectroscopy, FTIR, and microscopic techniques such as SEM, and EDX, confirming their crystalline structure, spherical morphology, and a nanoscale size of 19.85 nm. FTIR analysis identified functional groups such as flavonoids, phenolics, and proteins, suggesting their role in nanoparticle stabilization and biological activity. Biocompatibility assays demonstrated minimal hemolysis (0.109 ± 0.05% at 400 µg/mL), indicating safety for biomedical use. Antileishmanial activity against Leishmania tropica (a flagellate parasite) revealed concentration-dependent inhibition, with IC50 values of 250 µg/ml and 224 µg/ml for promastigotes and amastigotes, correspondingly. Cytotoxic effects on HepG2 liver cancer cells were evaluated using MTT and crystal violet assays, showing significant dose-dependent reduction in cell viability (IC50 = 50 µg/mL) and apoptosis induction. Furthermore, comparative MTT assays confirmed enhanced efficacy of nanoparticles synthesized with Chlorophyllum molybdites. These results confirmed the multifaceted biomedical effeciacy of mycosynthesized nanoparticles, including anticancer and antiparasitic applications, while promoting sustainable nanoparticle synthesis.

Sorafenib, a multikinase inhibitor targeting cell growth and angiogenesis, was approved for advanced unresectable hepatocellular carcinoma (HCC) in 2007. This investigation aims to elucidate the involvement of aquaglyceroporin-7 (AQP7) in regulating sorafenib resistance (SR) in HCC. AQP7 was downregulated in HCC-SR cells. AQP7 upregulation inhibited lipid accumulation, enhanced the sorafenib sensitivity of SR cells, and improved immune evasion. TBX19 protein was elevated in HCC-SR cells, and TBX19 repressed AQP7 transcription by binding to its promoter. E3-ubiquitin ligase MGRN1 was reduced in HCC, and its overexpression promoted TBX19 degradation. MGRN1 overexpression enhanced AQP7 and improved SR and immune evasion in HCC, which was reversed by TBX19 overexpression. Mouse HCC cells Hepa1-6 were used to construct an orthotopic tumor model and to analyze the effects of AQP7 and MGRN1 expression on the in vivo antitumor effects of Sorafenib, lipid accumulation in tumor tissues, and immune cell infiltration. MGRN1 silencing in Hepa1-6 cells induced sorafenib resistance and created an immunosuppressive tumor microenvironment, which was repressed by AQP7 upregulation. In conclusion, MGRN1 loss in HCC-SR cells blocked TBX19 degradation and strengthened TBX19-mediated AQP7 repression, leading to immune evasion. Targeting this signaling might offer a promising therapeutic strategy to overcome SR in HCC.

The emergence of multidrug-resistant pathogens underscores the urgent need for novel antimicrobial agents. In this study, ten endophytic fungal isolates (Ls1-Ls10) were isolated for the first time from Lavandula stricta and evaluated for their antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Klebsiella oxytoca, and Candida albicans. The most potent fungal isolate Ls1 was identified as Sarocladium kiliense using morphological and molecular techniques. Phytochemical analysis indicated that the S. kiliense extract is abundant in bioactive compounds, including phenolics, tannins, flavonoids, and alkaloids. The GC mass analysis proved the presence of 41 active compounds in the S. kiliense. Extract including; Benzene, (1-propylnonyl) (9.87%), Hexadecanoic acid (8.05%), Prostaglandin A1-biotin (6.77%), Docosene (6.69%), Octadecenoic acid (5.55%), and 1-Nonadecene (5.16%). The crude extract of S. kiliense showed outstanding anticancer activity against cancerous Hep-G2 and MCF-7 cell lines with IC50 of 31.7 and 49.8 µg/ml, respectively. This isolate exhibited significant antimicrobial activity, with inhibition zones ranging from 16.1 ± 0.1 mm to 35.5 mm. MICs varied between 62.5 and 250 µg/mL. S. kiliense exhibited antioxidant activity and antibiofilm activities. The S. kiliense extract demonstrated concentration-dependent antibiofilm activity. In conclusion, S. kiliense as a hopeful home of bioactive combinations with potent antimicrobial, antioxidant, anticancer, and antibiofilm activities, offering the potential for combating multidrug-resistant pathogens and therapeutic applications.

Erlotinib hydrochloride (ERL), a tyrosine kinase inhibitor, is effective in treating various cancers. However, low aqueous solubility limits its bioavailability and therapeutic efficacy. We developed an amorphous solid dispersion (ASD) of ERL with biocompatible polymers, polyvinylpyrrolidone (PVP-K30), and polyethylene glycol (PEG-4000) for enhanced amorphization, miscibility, and molecular interactions. The present study focuses on the physicochemical characterization of formulated ASD of ERL using Fourier Transform Infrared Spectroscopy (FTIR), X-ray Powder Diffraction (PXRD), UV-Visible Spectroscopy, and High-Performance Liquid Chromatography (HPLC), along with biological evaluation including antioxidant, cytotoxicity, and antitumor studies in mouse tumor models. FTIR analysis confirmed the retention of ERL's characteristic peaks in ASDs with PVP, PEG, and PVP/PEG, with shifts to lower frequencies for C=O bending, CH₂ deformation and CH symmetric deformation, indicating reduced molecular vibration energy, increased molecular flexibility, and strong drug-polymer interactions. PXRD analysis confirmed the transformation of crystalline ERL into an amorphous state in ASDs, as evidenced by the diminished ERL peaks at 11.7°, 16.2°, 21.7°, 24.75°, 25.56°, and 29.37°. UV spectroscopy revealed shifts in absorption peaks (256 nm), suggesting favorable drug-polymer interactions. HPLC demonstrated enhanced release rates at 4.72 retention time. In dissolution studies, the ERL + PEG formulation attained the greatest dissolution rate (80%). ERL + PVP showed superior DPPH radical scavenging activity with an IC50 value of 100 µg/mL, while ERL + PEG demonstrated stronger hydroxyl radical scavenging activity with an IC50 of 200 µg/mL. In the MTT assay, ERL + PEG exhibited the most potent cytotoxicity against MCF-7 cells, with an IC50 of 19 μM, whereas the ERL + PEG + PVP combination was most effective against HCT-116 cells, with IC50 of 19.5 μM. In vivo, ERL + PEG significantly reduced tumor volumes to 0.167 ± 0.002 g and 0.063 ± 0.004 g, corresponding to a tumor reduction of 98.78%. This study highlights the successful development of erlotinib ASD, particularly with PEG, which significantly improved ERL's solubility, dissolution rate, antioxidant activity, cytotoxicity, and antitumor efficacy. These enhancements are attributed to physical modifications such as enhanced amorphization and strong drug-polymer interactions, without any chemical alteration of ERL, underscoring the potential of this formulation as an effective and promising drug delivery strategy for cancer therapy.

The biosynthesis of silver nanoparticles has recently emerged as a promising approach in nanomedicine, particularly for targeted therapeutic applications. Green synthesized (plant-based) nanoparticles have been shown to offer enhanced reduction efficiency, greater bioavailability, and improved stability compared to synthetic nanoparticles. Here, we report the green synthesis of silver nanoparticles (AgNPs) using Magnolia alba leaf extract (MLE). The formation of these Magnolia-derived silver nanoparticles (MAgNPs) was verified through UV-Vis spectroscopy with a surface plasmon resonance peak at 440 nm, and further characterized by scanning electron microscopy, which showed that the MAgNPs have a mean diameter of 40 nm and a spherical morphology. MAgNPs exhibited significant antibacterial activity against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecalis, methicillin-resistant and -sensitive Staphylococcus aureus, with a minimum inhibitory concentration of 0.00043 mg/mL and a minimum bactericidal concentration of 0.00043 mg/mL and 0.0017 mg/mL, respectively. Disc diffusion and plaque assays with MAgNPs demonstrated strong antifungal activity against Candida albicans, with a zone of inhibition of 14 mm, and antiviral activity against T7 bacteriophage (p = 0.0004). In vitro studies with HCT-116 human colon cancer cells, MAgNPs exhibited bi-phasic, dose-dependent inhibition of viability with a 20-40% reduction, surpassing the positive control Camptothecin. Antioxidant assays indicated that MAgNPs showed significantly higher antioxidant activity compared to MLE, with enhanced Total Flavonoid Content (p = 0.0066), Total Phenol Content (p = 0.0013), and Total Antioxidant Capacity (p = 0.0051). Additionally, MAgNPs showed efficient photocatalytic degradation of the azo bond in methyl orange within 30 min. To our knowledge, this is the first report on the biosynthesis of MAgNPs and their multifunctional properties, highlighting the promise of MAgNPs in biomedical and environmental fields. (Insert attached Graphical abstract).

Quinazolinone derivatives exhibit significant synthetic and biological properties, making them valuable candidates for anticancer drug development. In this study, we synthesized novel quinazolinone derivatives via reactions of the previously unreported 4H-benzoxazin-4-one derivative (2) with various nitrogen nucleophiles, such as hydrazine hydrate and ammonium acetate, which yielded hydrazide and quinazolinone derivatives (3-6). Further modifications were achieved through reactions with carbon electrophiles and carbonyl compounds (e.g., phthalic anhydride, phenyl isothiocyanate, potassium cyanate, and pyrazole carbaldehyde), resulting in an expanded library of novel quinazolinone derivatives (7-15). The structures of all synthesized compounds were confirmed by spectroscopic and microanalytical techniques. In vitro cytotoxicity evaluations (mean IC50 ± SE, n = 3) revealed promising anticancer activity, with compounds 3 and 5 demonstrating the highest efficacy. To gain deeper mechanistic insights, molecular docking and molecular dynamics simulations were performed against key cancer-related targets, including Topoisomerase II, VEGFR2, c-Met, EGFR, and Estrogen Receptor Alpha. The combined experimental and computational findings suggest that these quinazolinone derivatives hold significant potential as novel anticancer agents, justifying further biological investigations and structural optimizations.

Herein, a novel compound 2-(3-methyl-5-oxo-1-phenyl-1,5-dihydro-4H-pyrazolylidene)-3-phenylthiazolidin-5-one )2(was synthesized and reacted with different aromatic aldehydes 3a-f via Knoevenagel condensation reaction to give the corresponding 4-arylidene-2-(5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene)thiazolidin-5-one hybrids 4a-f. The chemical structures were described by spectroscopic tools, IR, 1H NMR, 13C NMR, and MS. Their frontier molecular orbitals configuration and electron distribution were estimated to utilize DFT. The cytotoxicity of thiazolyl-pyrazole analogues 2 and 4a-f demonstrated in vitro antitumor activity toward breast cells; MCF-7 and MDA-MB231. Among the prepared analogues, the thiazolyl-pyrazole 2 revealed potent inhibitory toward the two cancer cells, particularly MDA-MB231 (IC50 = 22.84 µM). SwissADME studies showed the pharmacokinetic parameters, drug-like qualities, and bioavailability of these derivatives, revealing their potential in anticancer applications. Additionally, disease and drug target predictions and construction of the protein-protein interaction (PPI) network identified PPARG, EGFR, and PPARA as major targets. Moreover, other studies were carried out on the most potent conjugate 2 to evaluate the potential interactions against PPARG, EGFR, and PPARA proteins for molecular docking and against EGFR only for molecular dynamic simulation. The mechanism of the most effective analogue 2 was proven experimentally by inhibiting wound healing and EGFR expression in MDA-MB231 culture media. The findings provide more credence to compound 2's potential in current medication development initiatives.

The relationship between the changes in fibroid blood flow and fibroid diameter during the administration of GnRH agonists and antagonists was examined using superb microvascular imaging (SMI).

Immunotherapy is rapidly expanding to include a growing list of immune checkpoint inhibitors (ICIs) and indications for their use in the growing population of patients with cancer. Immune-related adverse events (irAEs) are common in patients receiving ICI therapy and greatly varied, affecting most organ systems. This diversity of symptoms that often mimic other disease processes and variable timeline of onset poses a particular challenge to emergency physicians in the acute care setting. This article presents a detailed overview of irAEs evaluation and management by organ system.

Chemotherapy is a cornerstone of cancer treatment. It routinely targets rapidly proliferating cancer cells, but can also affect healthy cells leading to various complications. This article explores different classes of chemotherapy medications and their most common side effects or complications. It also explores the most common effects on the body while undergoing chemotherapy treatment in general. This article emphasizes the complications of chemotherapy are numerous, range widely in severity, and are impacted by patient's underlying medical history.

Neutropenic fever is a life-threatening condition commonly associated with chemotherapy-induced neutropenia, requiring rapid diagnosis and immediate treatment. Risk stratification tools, such as the MASCC and CISNE scores, help clinicians identify high-risk patients and tailor management strategies. Future efforts should focus on integrating technological advancements, enhancing patient-centered care, and developing novel therapies to reduce recurrence and improve outcomes.

This study explores the green synthesis of zinc oxide nanoparticles (ZnONPs) using Tamarix chinensis extract, known for its hepatoprotective and anti-inflammatory phytochemicals. The ZnONPs were synthesized using ZnSO4 and NaOH, resulting in an average size of 125 nm, as confirmed by scanning electron microscopy (SEM). X-ray diffraction (XRD) analysis revealed a hexagonal crystalline structure. UV-Vis spectroscopy showed an absorption peak at 360 nm, corresponding to a bandgap of 3.37 eV, making these nanoparticles suitable for controlled drug delivery systems. The antioxidant activity of T. chinensis extract was evaluated using the DPPH assay, demonstrating an 80% inhibition of free radicals at 500 µg/mL, surpassing the antioxidant potential of the ZnONPs. The antimicrobial efficacy of the ZnONPs was evidenced by a minimum inhibitory concentration (MIC) of <50 µg/mL against Escherichia coli and Staphylococcus aureus. Additionally, the ZnONPs exhibited antiproliferative activity with an IC50 of 20.80 µg/mL in MCF-7 breast cancer cells, highlighting their potential for biomedical applications. These findings suggest the promising multifunctional role of biosynthesized ZnONPs in healthcare and technological innovations.

Understanding the dynamics of cancer cell growth, the interplay between tumor and immune cells, and the efficacy of chemotherapy are pivotal areas of focus in cancer research. In this regard, mathematical modeling can provide significant insights. This study re-examines a classical two-dimensional model of tumor-immune cell interactions where the tumor's growth rate is assumed to adhere to von Bertalanffy's model instead of the logistic model. We investigate the model both without chemotherapy and with treatment. The equilibrium points are identified, classified, and their stability analyzed. Our results reveal that the model can demonstrate a broad spectrum of behaviors, including bi-stability and multi-stability as well as regions of stable periodic behavior. We establish analytical conditions for the existence of Hopf points. Furthermore, we assess the impact of model parameters on the various behavior predicted by the model. This mathematical investigation can provide general guidance on treatment strategies.

It is becoming increasingly clear that newer chemotherapy treatments can significantly improve long-term survival rates for cancer patients. However, it is also becoming apparent that these treatments can be associated with long-term toxicities, including the possibility of cognitive decline. a number of factors may contribute to the development of cognitive impairment in cancer patients. It would seem that the symptom complex of chemotherapy-associated cognitive dysfunction, or 'chemobrain' as it is sometimes called in the international literature, is often underdiagnosed. This is despite the fact that it is one of the leading mental health problems in patients with malignant cancer. It is of the utmost importance that this issue is recognised and that appropriate management is put in place, as chemotherapy-associated neurocognitive impairment among people with cancer has the potential to significantly impair quality of life. In our non-systematic (narrative) summary study, we aim to provide a brief overview of the clinical picture and differential diagnosis of chemotherapy-associated neurocognitive impairment, as well as an overview of the main aspects of screening and treatment. We recognise that the characteristics of the symptomatic picture and the specific course of the disease raise a number of methodological issues that may be the subject of further empirical studies.

Intracystic IFNα proved to be a safe and effective option in the multimodal management of cystic craniopharyngioma (CRF).In our institutional experience, controversial cases have arisen concern and unanswered questions, that are becoming more common with the availability of new target therapies for other brain tumors.Reliable criteria to define the response to treatment should be defined. Additionally, the best timing of surgical resection after target therapy is not clear. Surgery is postponed in case of favorable response, but tumor relapse may present a different architecture eventually increasing surgical morbidity. Finally, in case of good response to the target therapy a close follow-up is required, since rebound may occur in exceptional cases.These data should represent the benchmark for future studies using either systemic administration of IFN or other intracystic drugs.

Acadesine (AICAR) is a promising candidate for new drugs in Phase III clinical trials. The purpose of this study is to analyse the steps in the biosynthesis pathway of AICAR. Our previous study found that overexpression of veA, a gene encoding a global regulator, significantly increased AICAR production of endophytic Fusarium solani HB1-J1 and the anti-tumor activity of its extracts. Transcriptome and metabolome analysis of FsveAOE14, a veA overexpressing F. solani strain, revealed a 10-step AICAR synthesis pathway, with adenylosuccinate lyase PurB as a key enzyme. Generally, overexpressing purB (the gene encoding adenylosuccinate lyase) enhances AICAR synthesis. However, in FsveAOE14, despite down-regulation of purB, AICAR content increased, which is contradictory. Further studies revealed that expression levels of purB homologs gene, pro06469 and pro10879, were upregulated in FsveAOE14. This suggests that although veA overexpression leads to purB down-regulation, their up-regulation may compensate for the reduction of purB, thus affecting AICAR synthesis. Additionally, compared to the wild type, overexpressing purB significantly enhances the inhibitory activity of the strain's extracts against the nonsmall-cell lung cancer cell line A549. Furthermore, it also increases the metabolic levels of other anti-tumor compounds, including 3-methyladenine, taurine, and others. These results indicate that VeA regulates AICAR biosynthesis via key enzymes like PurB, enhancing AICAR and other anti-tumor compound production, thus increasing the anti-tumor activity of F. solani extracts.

Tumor immunotherapy, a novel and rapidly progressing cancer treatment, has experienced remarkable advancements over recent years. It focuses on augmenting the patient's immune defenses and remodeling the immune microenvironment (IME) of tumors, rather than directly targeting malignant cells. The efficacy of immunotherapy relies substantially on multiple components within the tumor microenvironment (TME), extending beyond adaptive immunity alone. Immune cells within the TME play critical roles in both promoting immune surveillance and facilitating immune evasion. This complexity emphasizes the importance of immune checkpoint regulation in immunotherapeutic interventions. Therapeutically targeting specific immune cell subsets and metabolic pathways in combination treatments can transform an immunosuppressive TME into one that is immunologically activated, facilitating enhanced immune cell infiltration and consequently improving immunotherapy efficacy. Nevertheless, comprehensive research remains necessary to fully elucidate the mechanisms underlying TME interactions and immune checkpoint regulation, ultimately enabling more effective immunotherapeutic approaches.

Drug-induced sarcoidosis-like reaction (DISR) is a rare adverse event associated with immunotherapy. Currently, there is no standardized treatment protocol for DISR linked to immune checkpoint inhibitors (ICIs). This study presents a case of an early-stage triple-negative breast cancer (TNBC) patient who developed hepatic sarcoidosis-like reactions during neoadjuvant pembrolizumab therapy. We provide an overview of ICI-induced sarcoidosis-like reactions in cancer patients, including incidence, mechanisms, clinical manifestations, treatment, and prognosis. Additionally, we discuss the significance of one-year adjuvant immunotherapy for early-stage TNBC patients who achieved pathological complete response after neoadjuvant therapy, offering insights for individualized therapeutic strategies in this population.

Multiple studies have demonstrated that adjuvant therapy with programmed death-1 (PD-1) inhibitors can enhance the recurrence-free survival of patients with hepatocellular carcinoma (HCC) following curative resection. This study aims to assess the efficacy and safety of adjuvant tislelizumab (a PD-1 inhibitor), with or without tyrosine kinase inhibitors, in HCC patients at high risk of recurrence.

BackgroundCancer remains a leading cause of death worldwide, necessitating the development of affordable and innovative therapies to reduce its human and economic burden.ObjectivesIn this study, we aimed to develop a synergistic anticancer formula encapsulated in nanoliposomes to enhance efficacy and minimize side effects. Additionally, we explored the effect of aptamer conjugation on the efficacy and stability of the formula.MethodsThe Etoricoxib-β-cyclodextrin complex was prepared using the kneading method, and nanoliposomes were developed via thin film hydration. The AS1411 aptamer was conjugated to the nanoliposomes to target nucleolin, a protein overexpressed in cancer cells. The etoricoxib-β-cyclodextrin complex was characterized using proton nuclear magnetic resonance, and various liposome properties, including size, encapsulation efficiency, and stability, were optimized. The release profiles of the active compounds were evaluated using high-performance liquid chromatography, and their cytotoxicity was assessed in human cancer cell lines.ResultsThe nanoliposomes co-loaded with the three agents and their aptamer-conjugated counterpart showed optimal characteristics, with particle sizes of 133.3 ± 1.45 nm and 174.8 ± 4.78 nm, and zeta potentials of -15.26 ± 1.80 mV and -15.66 ± 2.57 mV, respectively. The encapsulation efficiencies were 88.63% (raloxifene), 41.73% (etoricoxib), and 39.26% (naringin) without the aptamer, and 81.99%, 36.66%, and 38.33%, respectively, with the aptamer. The IC50 of the formula for the three co-loaded agents was 167.4 µg/mL for A549 cells and 2.6 µg/mL for MCF-7 cells. Cytotoxicity was further enhanced using their aptamer conjugate, particularly against the MDA-MB-231 cell line.ConclusionThe novel triple-drug-loaded, aptamer-conjugated nanoliposome formula may be a future cancer treatment strategy.