Anticancer Research Articles

Natural Products-Based Anticancer Agents: Synthesis and Anticancer Activities of Funtumine Amide/Sulfonamide Derivatives.

Funtumine is a pregnene-type steroidal alkaloid exhibiting moderate anticancer activity. To discover novel natural product-based anticancer drugs, a series of novel funtumine amide/sulfonamide derivatives were papered and identified using spectroscopic techniques. Additionally, the structures of compounds 2j, 3a, and 4k were further confirmed through X-ray diffraction analysis. Biological activity experiments conducted against three cancer cell lines revealed that several of the synthesized compounds demonstrated inhibition activities comparable to or exceeding those of the commercial anticancer agent, 5-Fluorouracil. Especially compound 4i demonstrated a notably strong growth inhibitory effect on HePG2 (IC50=14.89 μM) and HCT116 (IC50=15.67 μM) cell lines, while exhibiting minimal cytotoxicity towards human normal BEAS-2B cells. Preliminary structure-activity relationships (SARs) analysis indicated that the conversion of the carbonyl group at the C-20 position of funtumine to a hydroxyl group could yield more potent compounds.

Gallic Acid Alleviates Methotrexate‐Induced Oxidative Ovarian Damage in Rats

Although methotrexate (MTX) is an effective chemotherapeutic agent in the treatment of cancer, its use is limited due to the occurrence of systemic tissue toxicity, including those affecting the reproductive system. Gallic acid (GAL) is a phenolic compound that has been demonstrated to exert beneficial effects in a number of pathological conditions associated with oxidative stress (OS) in recent years. This study was designed to investigate the therapeutic potential of GAL in the treatment of ovarian damage caused by MTX. Adult female rats (n=30) were randomly allocated to five groups: control, MTX, MTX+GAL (2.5 and 5 mg/kg) and high-dose GAL only (5 mg/kg). In the MTX-containing groups, ovarian toxicity was induced by a single dose MTX (20 mg/kg) injection. In contrast, groups containing GAL received injection treatment for three days, starting on the second day. The levels of OS, inflammation and apoptosis in tissue samples collected on the fifth day of the experiment were quantified using spectrophotometric methods. The results showed that GAL treatment reduced the level of ovarian lipid peroxidation, inflammation, and apoptosis and promoted the ovarian antioxidant system in rats subjected to MTX. The results of this study indicate that GAL may have the potential to ameliorate MTX-associated oxidative and inflammatory ovarian damage. It is recommended that this ovoprotective effect of GAL be confirmed by more comprehensive preclinical studies.

Eco-friendly RP-HPLC approach for simultaneously estimating the promising combination of pentoxifylline and simvastatin in therapeutic potential for breast cancer: Appraisal of greenness, whiteness, and Box–Behnken design

Abstract Breast cancer affects millions of women worldwide. This study explores the potential of combining pentoxifylline (PTX) and simvastatin (SIM) as a treatment for breast cancer. We aimed to develop six sustainability tools using green and white metrics to evaluate the environmental impact of reversed-phase high-performance liquid chromatography (RP-HPLC) methods for analyzing and separating PTX and SIM in their pure forms. The tools include analytical GREEnness, green analytical procedure index, Complexgreen analytical procedure index, analytical greenness metric for sample preparation, blue applicability grade index, and the RGB 12 algorithm. For the separation, we used a Novapack C8 column (15 × 0.46 cm, 5 µm) at 25°C. The injection volume was 5.0 µL, the wavelength was set to 210 nm, and the total runtime was 5 min. We identified optimal chromatographic conditions efficiently using the Box–Behnken design with minimal trials. We investigated the effects of three factors on retention time and resolution: acetonitrile ratio, pH, and flow rate. We used overlay plots with a 60:40 ratio (v/v) of acetonitrile and bi-distilled water to forecast the most effective mobile phase. The calibration curves for PTX and SIM showed a correlation value of over 0.999 within the range of 5–60 µg·mL−1. The recovery rates ranged from 99.9% to 100.2%, indicating high accuracy. Our RP-HPLC technique proves to be reliable and efficient for the simultaneous estimation of multiple anticancer drugs. We evaluated the environmental sustainability of this approach using green and white metrics, and the recommended method has been thoroughly validated according to International Council for Harmonisation guidelines, making it highly reliable for analyzing new formulations.

Design, Synthesis, and Evaluation of EA-Sulfonamides and Indazole-Sulfonamides as Promising Anticancer Agents: Molecular Docking, ADME Prediction, and Molecular Dynamics Simulations

New EA-sulfonamides and indazole-sulfonamides were synthesized, characterized, and evaluated for their anticancer activities. The target compound structures were elucidated using various spectroscopic techniques such as NMR-{1H and 13C}, infrared spectroscopy, and high-resolution mass spectrometry. The anticancer activities of the novel compounds were evaluated against four human cancer cell lines, namely A-549, MCF-7, Hs-683, and SK-MEL-28 as well as the normal cell line HaCaT, using 5-fluorouracil and etoposide as reference drugs. Among the tested compounds, 9, 10, and 13 exhibited potent anticancer activities which are better than or similar to the reference compounds 5-fluorouracil and etoposide, against the A-549, MCF-7, and Hs-683 cancer cell lines, with IC50 values ranging from 0.1 to 1 μM. Molecular docking studies of compounds 9, 10, and 13 showed a strong binding with selected protein kinase targets, which are linked to the tested cancer types. Furthermore, the analysis of the molecular dynamics simulation results demonstrated that compound 9 exhibits significant stability when bound to both JAK3 and ROCK1 kinases. This new compound has the potential to be developed as a novel therapeutic agent against various cancers.

Analysis of the nursing effect of five-tone therapy combined with acupoint massage on chemotherapy of lung cancer

BACKGROUND: The use of complementary therapies to relieve the side effects of chemotherapy in lung cancer patients is becoming increasingly popular. Practices from traditional Chinese medicine, such as acupoint massage and five-tone therapy, have demonstrated potential in alleviating symptoms such as nausea and vomiting experienced during chemotherapy. OBJECTIVE: This study aims to determine the effectiveness of combining five-tone therapy with acupoint massage in reducing chemotherapy-related symptoms in lung cancer patients. The main objective is to determine how these complementary therapies affect the quality of life and well-being of people undergoing chemotherapy for lung cancer. METHODS: In this paper, 80 patients diagnosed with lung cancer who needed chemotherapy drugs were randomly divided into 2 groups, 40 patients. The first was treatment; the second was control. Chemotherapy drugs were combined with a 5-hydroxytryptamine blocker (granisetron), and acupoint massage was combined with pentatone therapy to prevent nausea, vomiting, and other gastrointestinal reactions. A 5-hydroxytryptamine blocker (granisetron) was combined with chemotherapy drugs to prevent nausea, vomiting, and other gastrointestinal reactions. Moreover, the difference in treatment effect was observed. RESULTS: Among 40 cases in treatment, 13 cases were clinically controlled, 15 cases were markedly effective, 9 cases were effective, and 3 cases were ineffective. The total effective rate was 92.50%; among 40 cases in control, 6 cases were clinically controlled, 16 cases were markedly effective, 12 cases were practical, and 6 cases were invalid. The total effective rate was 85.00%. CONCLUSION: By integrating traditional Chinese medicine techniques, healthcare professionals can augment the supportive care offered to those undergoing chemotherapy for lung cancer.

Overexpression of CDCA8 predicts poor prognosis and drug insensitivity in lung adenocarcinoma

BackgroundLung adenocarcinoma (LUAD) accounts for the highest proportion of lung cancers; however, specific biomarkers are lacking for diagnosis, treatment, and prognostic assessment. Cell division cycle-associated 8 (CDCA8) is a cell cycle regulator with elevated expression in various cancers. However, the association between CDCA8 expression and LUAD prognosis remains unclear.MethodsThe association between CDCA8 and LUAD prognosis was evaluated based on the The Cancer Genome Atlas (TCGA) dataset, and CDCA8 related functions were determined using gene enrichment and gene ontology analyses. We also analyzed the association between CDCA8 expression and immune cell infiltration. Immunohistochemistry was used to determine the differential expression of CDCA8 in tumors and controls. Finally, we evaluated the differences in the sensitivity of different levels of CDCA8 to different anticancer drugs in LUAD.ResultsCDCA8 expression was significantly higher in primary LUAD tumors than in normal tissues (P < 0.001). Moreover, Kaplan–Meier survival analysis demonstrated that high CDCA8 expression predicted poor survival in patients with LUAD (P = 0.006). The receiver operating characteristic (ROC) curves indicated that CDCA8 was an effective guide for the diagnosis of LUAD. Functional annotation indicated that CDCA8 might be involved in functions such as p53 stabilization, nucleotide metabolism, RNA-mediated gene silencing, and the G2/M phase checkpoint. Immune infiltration results suggested that CDCA8 was positively correlated with Th2 cells and Tgd and negatively correlated with Eosinophils and Mast cells (P < 0.01). In addition, elevated expression of CDCA8 may increase the sensitivity of patients to certain anticancer drugs.ConclusionsCDCA8 upregulation is significantly associated with poor survival and immune infiltration in patients with LUAD. Our study suggests that CDCA8 can be used as a biomarker for LUAD prognosis and a reference for personalized medication.Graphical

Optimized Liquid Medium Formulation for Sanghuangporus vaninii and Biological Activity of the Exopolysaccharides

Aims: Sanghuangporus vaninii (S. vaninii) is a rare medicinal mushroom that is rich in polysaccharides, triterpenes, flavonoids, and other bioactive compounds. It has good potential development value. Methods and Results: We performed single factor experiments and Box-Behnken response surface methodology to optimize the liquid fermentation medium formulation for S. vaninii with mycelial biomass as the indicator. The in vitro antioxidant and anti-cancer capacity of the exopolysaccharides of S. vaninii were estimated. The optimal liquid fermentation media composition for the MS-4, MS-6, and MS-8 strains of Sanghuangporus vaninii consisted of 25.86 ± 0.068 g/L maltose, 7.3 ± 0.043 g/L yeast extract, and 0.71 ± 0.005 g/L dandelion powder. The average mycelial biomass of S. vaninii under optimal conditions was 12.61 g/L. The mycelial biomass of the Sanghuangporus vaninii strains in the optimized formulation was 109–191% higher than that obtained with the basic potato dextrose broth (PDB). The exopolysaccharides of Sanghuangporus vaninii exhibited an ABTS radical scavenging activity with an EC50 of 0.021 ± 0.017 mg/mL and a DPPH radical scavenging activity with an EC50 of 0.076 ± 0.043 mg/mL. In anti-cancer assays, these exopolysaccharides demonstrated an IC50 value of 1.98 ± 0.36 mg/mL against PC-3 human prostate cancer cells, indicating significant bioactivity, highlighting their potential as functional food ingredients. Conclusions: In this study, the formula of liquid fermentation of S. vaninii strains was optimized, which lays a theoretical foundation for increasing the yield of S. vaninii and its application in industry. Moreover, our data showed the clinical potential of the S. vaninii exopolysaccharides as antioxidants and anti-cancer drugs.

Cancer survivors and cardiovascular diseases: from preventive strategies to treatment.

During the last decades, progress in the treatment of oncological diseases has led to an increase in the survival of cancer patients: cancer survivors (CS). Thus, the incidence of CS has increased enormously, in both adult CS and childhood and adolescent CS. Unfortunately, CS treated with anthracyclines, chest radiotherapy (RT) and other potentially cardiotoxic drugs have a higher risk of cardiovascular (CV) toxicity: heart failure with reduced ejection fraction (HFrEF), valve diseases, coronary artery diseases, vascular diseases and pericardial diseases. In fact, chest irradiation can cause coronary artery diseases that can be latent until at least 10 years after exposure; also, valvular heart diseases can appear after >20 years following irradiation; heart failure may appear later, several years after anticancer drugs or RT. Therefore, it is very important to stratify the CV risk of cancer patients at the end of cardiotoxic drugs, to plan the most appropriate long-term surveillance program, in accordance with 2022 ESC Guidelines on Cardio-Oncology, to prevent late cardiovascular complications. Monitoring of cancer patients must not stop during anticancer treatment but it must continue afterwards, depending on the patient's CV risk. CV toxicity risk should be reassessed 5 years after therapy to organize long-term follow-up. Considering late cardiotoxicity in CS, our review aims to evaluate the incidence of cardiovascular diseases in CS, their mechanisms, surveillance protocols, preventive strategies, diagnosis and treatment.

Stability of immobilized L-arginine deiminase from Penicillium chrysogenum and evaluation of its anticancer activity

The aim of the present work was to immobilize L-arginine deiminase on suitable supports such as chitosan, alginate, and silica gel to study its stability. Additionally, the study aims to investigate the anticancer effects of the free purified enzyme on hepatocellular carcinoma (Hep-G2) and breast cancer (MCF-7) cell lines. L-arginine deiminase (ADI: EC 3.5.3.6) was immobilized on chitosan, Ca-alginate, and silica gel, with immobilization efficiencies of 89.0%, 72.8%, and 66.5%, respectively. The optimal immobilization time for the highest efficiency was 4 h. Increasing the concentration of glutaraldehyde improved the immobilization efficiency of ADI on chitosan. The chitosan-immobilized ADI retained about 45% of its activity after 8 cycles. The optimal pH values were 6 for the free purified ADI and 7 for the chitosan-immobilized ADI. The optimal temperature increased from 40 °C for the free enzyme to 45 °C after immobilization. The activation energies for the free and chitosan-immobilized enzymes were 71.335 kJ/mol and 64.011 kJ/mol, respectively. The Km values for the free and chitosan-immobilized ADI were 0.76 mM and 0.77 mM, respectively, while the Vmax values were 80.0 U/mg protein for the free ADI and 71.4 U/mg protein for the chitosan-immobilized ADI. After 30 days of storage at 4 °C, the residual activities were 40% for the free purified ADI and 84% for the chitosan-immobilized ADI. At 25 °C, the residual activities were 10% for the free ADI and 75% for the chitosan-immobilized ADI. The chitosan-immobilized ADI exhibited significantly higher stability against proteases such as pepsin and trypsin compared to the free enzyme. The purified ADI also demonstrated enhanced potential anticancer effects and significant cytotoxicity against the Hep-G2 and MCF-7 tumor cell lines compared to doxorubicin. These findings suggest that purified ADI has potential as an anticancer agent, though further in-depth studies are required.

Facile fabrication of dasatinib laden multifunctional polymeric micelles: Evaluation of anti‐proliferative and apoptotic activities in human cancer cells

AbstractDasatinib (DAS) has recently gained significant interest for its anticancer potential. Yet, the lipophilicity inherent in DAS limited its potential use as a chemotherapeutic drug. This study aimed to examine the effectiveness of polyethylene glycol‐polycaprolactone (PEG‐PCL) as a nanocarrier for DAS to increase its anticancer capabilities. The DAS‐loaded PEG‐PCL nanoparticles (termed as DAS@PEG‐PCL NPs) were characterized using Fourier transform infrared (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). Morphological staining and MTT tests were employed to investigate drug‐loaded nanoparticles' apoptotic and anti‐proliferative effects. The MTT assay demonstrated that incorporating DAS onto PEG‐PCL NPs resulted in a dose‐dependent increase in cytotoxicity in A549 (lung cancer) and HeLa (cervical cancer) cells. The A549 cancer cells were analyzed for their morphology using the acridine orange/ethidium bromide (AO/EB) and DAPI staining techniques. Overall, these findings demonstrate that the polymeric PEG‐PCL nanoparticle systems hold great potential as a novel therapeutic strategy for cancer treatment.

Fabrication of a natural nanocomposite from Syzygium cumini and squid bone waste decorated with Cu-Nps for simultaneous use in the triple method of photodynamic/photothermal/chemotherapy.

This work reports a new nano platform made from natural materials. For this purpose, calcium carbonate nanoparticles derived from Persian Gulf squid bones as a drug carrier, Syzygium cumini (dye extracted from the fruit of the Persian Gulf trees) as a photosensitizer, and Doxorubicin as a chemotherapy drug have been used. In addition, copper nanoparticles were added to the above composition to increase the efficiency of photothermal treatment. For phototherapy, samples were irradiated by an 808 nm laser (1 W). The results show that nanocomposites play an influential role in the reactive oxygen species process, and an increase of 21 degrees in temperature during 15 minutes of laser radiation is effective in photodynamic/photothermal therapy. The drug loading capacity of the nanocomposite was calculated as 49%. This new nanocomposite for simultaneous photodynamic/photothermal/chemotherapy holds great promise for future cancer treatment due to its excellent potential in treatment and reduced systemic toxicity.&#xD.

Cytotoxic and Antibacterial Activity of Koninginins Isolated from the Mangrove-Derived Endophytic Fungus Trichoderma sp.

The search for bioactive compounds for the treatment of several diseases has led to the study of endophytic fungi. Neoplastic diseases are among the most significant health concerns due to their high mortality rate, and there is a dearth of efficacious pharmaceutical agents for the treatment of cancer. Gastric cancer is one of the most aggressive forms of cancer and is among those with the highest mortality rates in Brazil. Accordingly, the objective of this study was to identify compounds with cytotoxic activity from the mangrove-derived endophytic fungus Trichoderma sp. Isolation of the chemical compounds was conducted using chromatographic methods, while structural elucidation was achieved through the application of spectroscopic (NMR and UV) and spectrometric (MS) techniques. The fungus Trichoderma sp. was found to produce five distinct koninginins (A, B, C, E, and J). The organic phases of the extracts and isolated compounds were evaluated for their antimicrobial and cytotoxic potentials, respectively, through microdilution testing and the MTT method. In the cytotoxicity assay, both the AF extract and koninginin A demonstrated favorable outcomes, indicating their potential as promising anticancer therapeutic agents.

Design, synthesis, and cytotoxic activity of 2-amino-1,4-naphthoquinone-benzamide derivatives as apoptosis inducers

A new series of 2-amino-1,4-naphthoquinone-benzamides 5a-n was designed based on previously reported potent cytotoxic agents. These compounds were synthesized from the reaction of 1,4-naphthoquinone, 4-aminobenzoic acid, and appropriate amine derivatives in good yields. Cytotoxic activities of the target compounds 5a-n were evaluated against three cancer cell lines MDA-MB-231, SUIT-2, and HT-29 by MTT assay and the obtained in vitro data. All newly synthesized compounds were more potent than positive control cisplatin against MDA-MB-231 cell line and less potent than this control against SUIT-2 cell line. Moreover, most of the synthesized compounds were more potent than cisplatin against HT-29 cell line. Among the synthesized compounds, compound 5e was the most potent cytotoxic agent against all the three evaluated cell lines. Moreover, cell cycle analysis showed that derivatives 5f and 5l dose-dependently increase the percentage of sub-G1 cells. Induction of apoptosis as an important mechanism of anti-cancer drugs was confirmed morphologically in the most potent new compounds 5e, 5f, 5g, and 5l by Hoechst 33,258 staining.

Metal–Organic Framework and Biopolymer-Based Composite Hydrogel for Enhanced Encapsulation of Anticancer Drugs: A New Age Transdermal Drug Delivery Vehicle

Metal–Organic Framework and Biopolymer-Based Composite Hydrogel for Enhanced Encapsulation of Anticancer Drugs: A New Age Transdermal Drug Delivery Vehicle

The Antipsychotic Drug Aripiprazole Suppresses Colorectal Cancer by Targeting LAMP2a to Induce RNH1/miR-99a/mTOR-Mediated Autophagy and Apoptosis.

The mammalian target of rapamycin (mTOR) is a critical signaling hub for sustaining cancer survival. Targeting mTOR and inducing autophagic cell death downstream of it represent promising therapeutic strategies for cancer prevention. A US Food and Drug Administration-approved drug library containing 616 small molecules is used to screen anticancer drugs against colorectal cancer (CRC) cells that rely on mTOR. This led to the identification of an antipsychotic drug aripiprazole, which significantly induced mTOR inhibition and autophagic apoptosis in CRC, in vitro and in vivo. The use of drug affinity response target stability identified lysosome-associated membrane protein 2A (LAMP2a) as a direct target of aripiprazole. LAMP2a-deficient CRC cells are refractory to aripiprazole. High LAMP2a expression is associated with poor survival of patients with CRC and negatively correlated with expression of ribonuclease inhibitor 1 (RNH1), which is later confirmed as a novel substrate of LAMP2a. Mechanistically, aripiprazole bound to the Lys401-His404 of LAMP2a and repressed its activity, subsequently inactivating RNH1/miR-99a/mTOR signaling and inducing autophagy-mediated apoptosis, thereby suppressing tumorigenesis. Liposome-mediated delivery of aripiprazole in combination with fluorouracil elicited superior therapeutic benefits in CRC, as compared to single treatments, thereby highlighting that aripiprazole may be repurposed as a novel therapeutic agent for CRC treatment.

Biocompatible supramolecular hydrogels based on polysaccharide-modified hyaluronic acid for targeted delivering of doxorubicin

ABSTRACT In this paper, Biocompatible supramolecular hydrogels, composed of β-cyclodextrin-modified hyaluronic acid, pluronic F127, α-cyclodextrin and doxorubicin, were constructed, which can be employed for targeted delivery system. The chemical composition and rheological properties of the obtained hydrogels were fully characterised. Considering the controlled complexation between DOX and the hydrogel skeletons, the controlled release of hydrogel G[5, 10, 5] was investigated to exhibit a better pH- and temperature-controlled release behavior. The data of DOX release kinetic was fitted well with Higuchi and Korsmeyer-Peppas models. Moreover, the cellular toxicity experiments indicated that the hydrogel DOX@G[5, 10, 5] exhibited a similar anticancer ability in comparison with free DOX. Due to the hyaluronic acid-targeted effects, the cytotoxicity of the hydrogel DOX@G[5,10,5] to HepG2 cells was lower than that to SKOV-3 cells upon increasing the concentration. Therefore, these hydrogels may act as a potential prospect for the targeting release of anticancer drugs.

Importance of sex-dependent differences for dosing selection and optimization of chemotherapeutic drugs.

Background Despite major advances in cancer treatment in the past years, there is a need to optimize chemotherapeutic drugs dosing strategies to reduce toxicities, suboptimal responses, and the risk of relapse. Most cancer drugs have a narrow therapeutic index with substantial pharmacokinetics variability. Yet, current dosing approaches do not fully account for the complex pathophysiological characteristics of the patients. In this regard, the effect of sex on anticancer chemotherapeutic drugs disposition is still underexplored. In this article, we review sex differences in chemotherapeutic drug pharmacokinetics, we suggest a novel approach that integrates sex into the traditional a priori body-surface-area (BSA) dosing selection model and finally, we provide an overview of the potential benefits of a broader use of therapeutic drug monitoring (TDM) in oncology. Summary To date, anticancer chemotherapeutic drugs dosing is most often determined by BSA, a method widely used for of its ease-of-practice, despite criticism for not accounting for individual factors, notably sex. Anatomical, physiological, and biological differences between males and females can affect pharmacokinetics, including drug metabolism and clearance. At equivalent doses, females tend to display higher circulating exposure and more organ toxicities, which has been formally demonstrated at present for about 20% of chemotherapeutic drugs. An alternative could be the Sex-Adjusted-BSA (SA-BSA), incorporating a 10% increase in dosing for males and a 10% decrease for females, though this approach still lacks formal clinical validation. Another strategy to reduce treatment-related toxicity and potentially enhance clinical outcomes could be a more widespread use of therapeutic drug monitoring (TDM), for which a benefit has been demonstrated for 5-fluorouracil, busulfan, methotrexate or thiopurines.

Diffuse lung diseases ascribed to drugs: a nationwide observational study over 37 years using the French pharmacovigilance database.

Drug-induced interstitial lung disease (DI-ILD) is a heterogeneous subgroup of interstitial lung diseases (ILD). The number of molecules involved is increasing with time. Due to their low incidence, DI-ILDs may be detected only after a drug has been marketed, notably through Adverse Drug Reaction (ADR) reports to pharmacovigilance centres. The aim of our study was to describe drug-induced diffuse lung disease cases notified to and recorded by the French Pharmacovigilance Database (FPVD), reported clinical pictures and the potentially causal drugs. This retrospective study included cases registered in the FPVD from 1st January 1985 to 1st April 2022 which had ADR coded in MedDRA with a High Level Group Term "Lower respiratory tract disorders (excluding obstruction and infection)" involving patients aged 18 and over. We analysed 7234 cases involving 13 059 suspect medications and 1112 specific molecules. Cases were categorised as serious in 96.7% and in 13.3% death ensued. Men accounted for 54.4% of the cases. Median age was 69 [18-103] years. The most prevalent ADRs were "ILD" (51.0%), "Pulmonary oedema" (acute/non-acute) (15.6%) and "Pulmonary fibrosis" (10.5%). "Anti-cancer drugs" (31.2%) and "Cardiovascular drugs" (29.1%) were the most prominent therapeutic classes involved, with amiodarone being the most commonly reported suspected drug (10.0%), followed by methotrexate (3.1%). This study from a large nationwide dataset spanning 37 years is the largest known to date. Drug-induced diffuse lung diseases are serious with a potentially fatal outcome. Accurate diagnoses remain essential to identify it properly and discontinue the culprit drug urgently.

RENOPROTECTIVE POTENTIAL OF FLAVONOIDS-RICH AGAINST DOXORUBICIN-INDUCED IN ANIMAL MODELS: A REVIEW

Cancer significantly impacts human health, affecting one in five people during their lifetime. While chemotherapeutic agents like doxorubicin are crucial in treating various cancers, they are also associated with severe side effects, including nephrotoxicity. This review examines the renoprotective potential of flavonoids against doxorubicin-induced renal damage in animal models. Doxorubicin works by intercalating Deoxyribo Nucleic Acid (DNA) and making Reactive Oxygen Species (ROS), which cause apoptosis and the death of cells. A thorough literature analysis was done to collect relevant papers on the impact of flavonoid-rich therapies as renoprotective agents against doxorubicin-induced nephrotoxicity. Databases such as Google Scholar, Scopus, PubMed, Springer, Wiley Online Library, and ScienceDirect were searched using keywords including "flavonoids, doxorubicin, renoprotective, nephrotoxicity, and animal model," focusing on publications from 2014 to 2024. Flavonoids are diverse polyphenolic compounds in many plants with significant pharmacological properties such as antioxidant, anti-inflammatory, and anticancer effects. This review highlights the renoprotective potential of flavonoids like quercetin, rutin, kaempferol, morin, luteolin, apigenin, hesperidin, naringenin, diosmin, and anthocyanins. These compounds reduce renal toxicity through mechanisms that decrease ROS, lipid peroxidation, mitochondrial permeability, and apoptosis.

Chitosan-coated nanoemulsion for intranasal administration increases temozolomide mucosal permeation, cellular uptake, and In vitro cytotoxicity in glioblastoma multiforme cells

Glioblastoma multiforme (GBM) is the most prevalent and aggressive type of brain cancer in adults. Temozolomide (TMZ) is the chemotherapeutic agent used to treat primary central nervous system tumors. However, TMZ's clinical effectiveness faces several challenges due to its physical-chemical properties and biological features of GBM, such as the blood-brain barrier (BBB). Mucoadhesive nanosystems such as those coated with chitosan represent a promising alternative for optimizing the delivery of therapeutic agents to the central nervous system, as they possess ideal characteristics that enhance their interaction with the intranasal mucosa. We aimed to develop a chitosan-coated nanoemulsion containing temozolomide (CS-NE-TMZ) for nose-to-brain delivery and characterize its physical-chemical and in vitro biological properties. CS-NE-TMZ were obtained by emulsification followed by sonication. The optimized CS-NE-TMZ presented droplet size of 123,4 ± 2,3 nm, polydispersity index of 0.273 ± 0.028, zeta potential of +21,5 ± 0,81 mV, entrapment efficiency of 100 ± 1,91 % and drug loading of 2 ± 0,007 %. An in vitro release study of CS-NE-TMZ showed sustained release for up to 24 h following the Korsmeyer-Peppas model with Fickian diffusion. CS-NE-TMZ demonstrated significantly enhanced ex vivo mucosal permeation, compared to free TMZ, and showed enhanced in vitro cellular uptake, selectively increasing cytotoxicity in U-87MG glioma cells but not in healthy L929 fibroblasts, reinforcing the potential of mucoadhesive nanoemulsions as effective intranasal drug delivery systems for future brain cancer therapies.