Cytotoxicity In Cell Lines Research Articles

Topical delivery of siRNA to psoriatic skin model using high molecular weight chitosan derivatives: In vitro and in vivo studies.

Psoriasis is a chronic inflammatory skin disease that, like other immune-mediated conditions, may benefit from small interfering RNA (siRNA)-based therapies, which are emerging as a promising alternative by addressing several limitations of current treatments. In this study, topical formulations of chitosan-based vectors were developed to deliver siRNA targeting tumor necrosis factor alpha (TNFα) to inflamed skin. Grafting diisopropylethylamine (DIPEA) and polyethylene glycol (PEG) onto the chitosan backbone enhanced siRNA delivery efficiency under physiological conditions, forming robust polymeric vectors with high structural and colloidal stability. These vectors provided siRNA protection against RNAse degradation and oxidative damage. Additionally, the chitosan derivatives displayed lysozyme-mediated biodegradability comparable to native chitosan, while PEG was released in response to reductive environments, supporting controlled vector disassembly. The PEGylated DIPEA-chitosan/siRNA polyplexes demonstrated positive zeta potentials (up to + 11 mV), particle sizes of 100-200nm, and very low cytotoxicity in keratinocyte and fibroblast cell lines. In vitro, the polyplexes achieved TNFα knockdown levels (65%) in RAW macrophages, comparable to those obtained with Lipofectamine™. Topical formulations showed enhanced interaction of vectors with skin models (Strat-M® and porcine ear skin) compared to naked siRNA. Furthermore, in vivo studies indicated that hair follicles were a key route for polyplexes to penetrate deeper skin layers. A rodent model of psoriasis induced by imiquimod was treated topically with these vectors, resulting in approximately a 50% reduction in TNFα levels at inflammation sites, decreased immune cell infiltration, and preservation of epidermal structure. These findings collectively underscore the potential of DIPEA-chitosan-based vectors for topical siRNA-based therapies.

Effects of hypoxia and iron on ascorbic acid-mediated cytotoxicity in prostate cancer cell lines

Effects of hypoxia and iron on ascorbic acid-mediated cytotoxicity in prostate cancer cell lines

Anticancer Activity and GC-MS Profiling of Bioactive Constituents in the Methanolic Extracts of Spatoglossum variabile and Gracilaria corticata

Background: Marine algae stand out as repositories of bioactive metabolites, widely harnessed in treating diverse diseases. Given the often-challenging side effects associated with conventional cancer treatments, researchers are increasingly turning their attention to marine algae as a promising source for discovering novel and potent anticancer compounds. In this study, we meticulously explored the potential anticancer activity of Spatoglossum variabile and Gracilaria corticata sourced from the Indian Ocean. Materials and Methods: The secondary metabolites were extracted using methanol solvent according to the standard protocol. The extract was subjected to GC-MS analysis and evaluated for its short- and long-term cytotoxicity and anti-proliferative ability in the HCT116 cell line using MTT, clonogenic, and trypan blue dye exclusion assays, respectively. Results and Discussion: The methanolic extract of Spatoglossum variabile contained 21 unique anticancer compounds, except for the other bioactive compounds. The results indicate that increasing the concentration of algal extracts decreased the cell viability significantly, with an IC50 of 51.49 μg/mL and 37.50 μg /mL in the HCT116 cell line. The results showed a significant reduction in colorectal cancer colony formation and a gradual reduction in cell proliferation. These results underscore the potential for targeted, low-toxicity biomedicines due to their selective cytotoxicity against cancer cells. Conclusion: Our findings show that Spatoglosuum variabile & Gracilaria corticata extracts contain various bioactive compounds, display long-term and short-term cytotoxicity and antiproliferative effects, which indicates that their constituent compounds might be further refined into effective anti-colorectal cancer medications.

Investigation of the antibacterial activity, cytotoxicity, and effects on enamel and composite resin of mouthwash formulations prepared with three different Boron compounds.

This study investigated the use of oral rinse solutions formulated with boron-containing compounds, known for their antibacterial activity, as an alternative to chlorhexidine (CHX). Boron nitride (BN), boric acid (BA) and sodium borate (SB) were used in the study. BN was used in nanosuspension (BN-NS) due to its low solubility in water. BA and SB were also prepared and used in solution form (BA-S, SB-S). Antibacterial activity against cariogenic bacteria was evaluated using agar well diffusion and microdilution techniques, and antibiofilm activity was evaluated using the crystal violet method. Cytotoxicity in human gingival cell lines (HGF-1) was evaluated using MTT and LDH assays. Surface hardness was measured with Vicker's Microhardness tester and surface roughness was measured with a profilometer. CHX was used as the control group. BN-NS, BA-S, and SB-S showed antibacterial and antibiofilm activity against all cariogenic bacteria. BN-NS and SB-S demonstrated much lower cytotoxicity compared to CHX, while BA-S exhibited similar cytotoxicity. SB-S caused an increase in enamel surface hardness (p = 0.017), whereas no significant changes were observed in surface roughness or hardness in the other groups (p > 0.05). BN-NS and SB-S showed antibacterial effects and antibiofilm activity on all tested cariogenic bacteria. BN-NS and SB-S showed lower cytotoxicity than CHX, and their effects on enamel and composite resin surfaces were similar to the control group. Further studies are needed to support the use of BN-NS and SB-S as alternatives to CHX. BN-NS and SB-S are promising alternatives to the antibacterial agent CHX, which is known to be cytotoxic.

Endoglin as a predictive biomarker for pemetrexed sensitivity in non-small-cell lung cancer: a cellular study.

Based on our previous research, which demonstrated that elevated plasma endoglin (ENG) levels in lung cancer patients were associated with a better prognosis, increased sensitivity to pemetrexed, and enhanced tumor suppression, this study aims to validate these findings at the cellular level. The focus is on membrane and extracellular ENG and their influence on drug response and tumor cell behavior in non-small cell lung cancer (NSCLC) cells. The correlation between ENG expression and pemetrexed-induced cytotoxicity in eight human non-squamous subtype NSCLC cell lines was analyzed. ENG in A549 and H1975 cells was knocked down using shRNA. MTT assay, cell cycle assay, western blot analysis, and boyden chamber assay were used to detect the effect of ENG on pemetrexed-induced cytotoxicity, cell cycle distribution, and cell migration. The expression of membrane ENG was positively correlated with pemetrexed-induced cytotoxicity in human NSCLC cells. Compared to pemetrexed-sensitive A549 cells, the A549/a400 (pemetrexed-resistant subline) cells exhibited a reduced accumulation of cells in the S phase, making them less susceptible to cell death. ENG knockdown also alleviated pemetrexed-induced S phase arrest and regulated G1/S phase-related proteins (p53, p21, CDK2, and Cyclin A). Additionally, co-treatment with recombinant ENG enhanced pemetrexed-induced migration inhibition in the sensitive cel1 line and cytotoxicity in the resistance cell line. The present results strengthened our prior clinical findings, showing that higher membrane ENG expression enhances pemetrexed-induced cytotoxicity and S phase arrest, which may involve the ENG-p21 pathway. Additionally, microenvironmental ENG enhanced the anti-migration of pemetrexed. These findings highlight the potential of ENG as a biomarker and therapeutic target, opening new avenues to improve the outcomes of non-squamous cell NSCLC treatment.

Isolation of New Strains of Lactic Acid Bacteria from the Vaginal Microbiome of Postmenopausal Women and their Probiotic Characteristics

Lactic acid bacteria (LAB), traditionally consumed as fermented foods, are now being applied to the medical field beyond health-functional food as probiotics. Therefore, it is necessary to continuously discover and evaluate new strains with suitable probiotic characteristics, mainly focusing on safety. In this study, we isolated eight new strains from postmenopausal vaginal fluid using culturomics approaches, an emerging area of interest. Data showed that most strains possessed significant cell surface hydrophobicity (≥ 76%), auto-aggregation capacity (17 to 61%), strong adhesion activity (8 to 34%), and excellent resistance to gastric acid, bile salt, and digestive enzyme, enhancing their survival in the gastrointestinal tract. Moreover, the strains exhibited functional characteristics, including substantial antibacterial activity with a minimal inhibitory concentration (MIC) ranging from 12.5 to 50%. They also harbored bacteriocins genes, produced short-chain fatty acids (acetate and propionate), exhibited significant phagocytic activity, possessed high antioxidative properties, rapidly depleted sodium nitrite, and exhibited proteolysis and β-glucosidase activity. In addition, heat-killed LAB strains significantly reduced the gene expressions of proinflammatory cytokines such as IL-β, IL-6, and iNOS in macrophages. Safety assessment revealed no cytotoxicity in macrophage cell lines. All strains tested negative for biogenic amine or H2O2 production, displayed no gelatinase or hemolytic activity, lacked virulence genes or detrimental enzymes, and displayed antibiotic susceptibility. In summary, these newly isolated strains demonstrate excellent probiotic functionality with a strong focus on safety, making them promising candidates for future drug development in the relevant fields.

Integrated Network Pharmacology, Machine Learning and Experimental Validation to Identify the Key Targets and Compounds of TiaoShenGongJian for the Treatment of Breast Cancer.

TiaoShenGongJian (TSGJ) decoction, a traditional Chinese medicine for breast cancer, has unknown active compounds, targets, and mechanisms. This study identifies TSGJ's key targets and compounds for breast cancer treatment through network pharmacology, machine learning, and experimental validation. Bioactive components and targets of TSGJ were identified from the TCMSP database, and breast cancer-related targets from GeneCards, PharmGkb, and RNA-seq datasets. Intersection of these targets revealed therapeutic targets of TSGJ. PPI analysis was performed via STRING, and machine learning methods (SVM, RF, GLM, XGBoost) identified key targets, validated by GSE70905, GSE70947, GSE22820, and TCGA-BRCA datasets. Pathway analyses and molecular docking were performed. TSGJ and core compounds' effectiveness was confirmed by MTT and RT-qPCR assays. 160 common targets of TSGJ were identified, with 30hub targets from PPI analysis. Five predictive targets (HIF1A, CASP8, FOS, EGFR, PPARG) were screened via SVM. Their diagnostic, biomarker, immune, and clinical values were validated. Quercetin, luteolin, and baicalein were identified as core components. Molecular docking confirmed their strong affinities with predicted targets. These compounds modulated key targets and induced cytotoxicity in breast cancer cell lines in a similar way as TSGJ. This study reveals the main active components and targets of TSGJ against breast cancer, supporting its potential for breast cancer prevention and treatment.

Elucidating the leaching effect of micro/nanoplastics on the binding, structural, and oxidative characteristics of bovine serum albumin, and impact on cytotoxicity and oxidative stress in the human lung cancer cell line, A549

Proteins like albumin are found in various environmental, living systems, and applications. It is known that functional, conformational and sorption properties of proteins are significantly affected by various surrounding conditions...

Synthesis of novel pyrrolobenzodiazepine (PBD) C1-substituted monomers and dimers with DNA-binding activity and cytotoxicity.

The pyrrolobenzodiazepines (PBDs) represent a major class of sequence-selective DNA-alkylating molecules, one example of which, in its dimeric DNA-cross-linking form, is employed as the payload in the anticancer Antibody Drug Conjugate (ADC) loncastuximab tesirine-lpyl. To date, PBD analogues have been produced with substituents at every position of the tricyclic skeleton except the C1-position. We report here the first synthesis of a C1-subsitituted PBD monomer and dimer, both of which possess DNA-binding activity and cytotoxicity in a cancer cell line.

Sulphonyl thiourea compounds containing pyrimidine as dual inhibitors of I, II, IX, and XII carbonic anhydrases and cancer cell lines: synthesis, characterization and in silico studies.

Some novel sulphonyl thiourea derivatives (7a-m) containing 4,6-diarylpyrimidine rings were designed and synthesized using a one-pot procedure. These compounds exhibited remarkable dual inhibitory activity against human carbonic anhydrase hCA I, hCA II, hCA IX, and XII isoenzymes and some cancer cell lines. Among them, some thioureas had significantly more potent inhibitory activities in the order of 7l > 7c > 7f (against the hCA I isoform), 7f > 7b > 7c (against the hCA II isoform), 7c > 7g > 7a > 7b (against the hCA IX isoform), and 7d > 7c > 7g > 7f (against the hCA XII isoform). The obtained inhibitory activity data against the hCA IX and XII isoforms showed that compound 7c was the most potent inhibitor in this sulphonyl thiourea series against enzyme hCA IX, with K I = 125.1 ± 12.4 nM, while compound 7d was the most potent inhibitor against enzyme hCA XII, with K I = 111.0 ± 12.3 nM. Compound 7c exhibited strong inhibitory activity among all four tested hCA enzymes, while thiourea 7f was a potent inhibitor for enzymes hCA I, II and XII. All these compounds demonstrated non-competitive inhibition of both enzymes. Some selected potential inhibitory compounds, including 7c, 7d, and 7g, exhibited remarkable cytotoxic activity against human cancer cell lines, including human breast adenocarcinoma (MCF-7), human liver adenocarcinoma (HepG2), human cervical epithelial carcinoma (HeLa), and human lung adenocarcinoma cells (A549). These compounds exhibited low cytotoxicity in the WI-38 cell line. The compounds 7c and 7d were the most potent inhibitors against tumour-associated hCA IX and hCA XII isoenzymes. Furthermore, these compounds exhibited remarkable inhibition against some cancer cell lines, such as MCF-7, HepG2, HeLa, and A549. They were subjected to in silico screening for molecular docking and molecular dynamics simulations. The results of in vitro and in silico studies revealed that compounds 7c and 7d were the most promising derivatives in this series owing to their significant effects on the studied hCA IX and hCA XII isoenzymes, respectively. The results showed that the sulphonyl thiourea moiety was deeply accommodated in the active site and interacted with zinc ions in the receptors.

Efficacy of GABA aminotransferase inactivator OV329 in models of neuropathic and inflammatory pain without tolerance or addiction

Dysregulation of GABAergic inhibition is associated with pathological pain. Consequently, enhancement of GABAergic transmission represents a potential analgesic strategy. However, therapeutic potential of current GABA agonists and modulators is limited by unwanted side effects. We postulated that inhibition of GABA's degradation enzyme, GABA aminotransferase (GABA-AT), would increase endogenous GABA levels and produce analgesia. We evaluated antinociceptive efficacy of the potent GABA-AT inhibitor OV329 in rodent models of neuropathic and inflammatory pain and assessed possible side effects (i.e., reward and motor impairment). OV329 attenuated the development and maintenance of mechanical and cold hypersensitivities induced by the chemotherapeutic agent paclitaxel. Prophylactic OV329, administered systemically, normalized paclitaxel-induced increases in glutamate levels and suppressed neuropathic nociception. Intrathecal OV329 suppressed paclitaxel-induced mechanical hypersensitivity, elevating GABA, and reducing glutamate levels in the lumbar spinal cord, consistent with a spinal site of action. Furthermore, OV329 largely synergized with paclitaxel to enhance 4T1 tumor cell line cytotoxicity without altering viability of nontumor cells. OV329 also attenuated inflammation-induced mechanical hypersensitivity induced by intraplanar injection of complete Freund's adjuvant (CFA) with efficacy comparable to morphine. Unlike morphine, OV329 did not produce reward in a conditioned place preference assay in mice and was not self-administered intravenously by rats. Antinociceptive efficacy of OV329 was observed at doses that did not impair motor function or produce tolerance following chronic dosing. Thus, inhibition of GABA-AT with OV329 represents a unique therapeutic strategy to alleviate neuropathic and inflammatory pain with no apparent abuse liability, potentially producing a beneficial spectrum of pharmacological effects through enzymatic regulation.

Theoretical determination of the biological activities of some benzimidazolederivative compounds with potential as active pharmaceutical agents

The biological activities of twelve different benzimidazole derivative compounds synthesized and registered in the literature were theoretically calculated with Way2Drug PASS software. Seven different biological activities, including acute rat toxicity, adverse drug effects, antibacterial activity, antifungal activity, anti-HIV activity, antiviral activity, and cell line cytotoxicity, were calculated for each benzimidazole derivative compound examined here. Rat acute toxicity was calculated in four different ways. These are Rat IP (intraperitoneal administration route) LD50, Rat IV (intravenous administration route) LD50, Rat Oral (oral administration route) LD50, and Rat SC (subcutaneous administration route) LD50. According to the results, a classification was also made for each method. Adverse effects that the molecules may show were determined with the help of the calculated Pa (probability of activity) and Pi (probability of inactivity) values. The antibacterial effect of each molecule against which bacteria was determined and the confidence value of this effect was calculated. Likewise, it was determined whether the molecules showed antifungal properties. It was determined against which fungus the molecules showing antifungal properties showed this effect, and the confidence value was calculated. The anti-HIV properties of the molecules were studied for five different targets (protease (HIV-1), reverse transcriptase (HIV-1), integrase (HIV-1), REV (regulator of virion) (HIV-1), and TAT (trans-activator of transcription) (HIV-1)) and the p function of the IC50 (half maximal inhibitory concentration) values obtained were analyzed. Anti-viral effects of molecules examined. Here, the viruses against which they show this effect were determined, and the confidence value was calculated together with the target protein. Finally, cancer cell line and non-tumor cell line properties of the molecules were determined by Pa and Pi values as well as tissue and tumor type.

Antiparasitic Activity of Coumarin-Chalcone (3-Cinnamoyl-2H-Chromen-2-Ones) Hybrids.

Coumarin-chalcone hybrids are promising compounds that could be used as lead structures in the fight against parasitic diseases. In this work, 16 hybrids of coumarin-chalcone (3-cinnamoyl-2H-chromen-2-ones) were synthesized, and their in vitro biological activity was evaluated against intracellular amastigotes of Leishmania braziliensis and Trypanosoma cruzi, as well as their cytotoxicity in the U-937 cell line. Compounds (E)-3-(3-(3-ethoxy-4-hydroxyphenyl)acryloyl)-7-methoxy-2H-chromen-2-one (H25) and (E)-7-(diethylamino)-3-(4-(methoxyphenyl)acryloyl)-2H-chromen-2-one (H12) showed the highest antileishmanial activity with EC50 values of 18.6±3.5 and 25.6±0.4µM, respectively. In general, all 16 compounds exhibited moderate-to-high antitrypanosomal activity. The H25 hybrid also demonstrated the greatest antitrypanosomal activity, with an EC50 value of 13.2±0.4µM. Notably, the H25 hybrid displayed activity similar to that of benznidazole, which is known for its antiparasitic effects against T. cruzi. The results indicated that all compounds met the drug-like properties criteria. Taking into account the high antiparasitic activity of H25, a molecular docking study with the enzyme trypanothione reductase was performed. The substituent at C7 in the coumarinyl system is an important structural requirement for the antileishmanial and antitrypanosomal activities.

Exploring Hypofractionated Radiotherapy Efficacy in Prostate Cancer: In Vitro Insights

The rising incidence of prostate cancer necessitates innovative treatment approaches, particularly as diseases such as the COVID-19 pandemic can disrupt traditional cancer care. This study aims to evaluate the impact of hypofractionated versus conventionally fractionated radiotherapy on prostate cancer cell lines in vitro. Prostate cancer cell lines (PC-3 and DU-145) were exposed to varying doses of radiation alongside non-cancerous BPH-1 cells. We assessed radiation effects on cell proliferation, viability, colony formation, DNA repair, migration, invasion, and cytotoxicity. The results demonstrated that the prostate cell lines exhibited varying responses, with hypofractionation favourably impacting aggressive PC-3 cells while preserving non-cancerous cells. In contrast, conventional fractionation led to increased invasion and cytotoxicity in both prostate cancerous cell lines. These findings advocate for personalised radiation therapy approaches that enhance treatment efficacy by considering the distinct behaviours of differing prostate cancer subtypes.

Rational design and synthesis of novel phenyltriazole derivatives targeting MRSA cell wall biosynthesis.

Antimicrobial resistance in methicillin-resistant Staphylococcus aureus (MRSA) is a major global health challenge. This study reports the design and synthesis of novel phenyltriazole derivatives as potential anti-MRSA agents. The new scaffold replaces the thiazole core with a 1,2,3-triazole ring, enhancing antimicrobial efficacy and physicochemical properties. A series of derivatives were synthesized and evaluated, with four compounds (20, 23, 29 and 30) showing significant activity against MRSA (MIC ≤ 4 μg mL-1). Compound 29 emerged as the most promising candidate, showing rapid bactericidal activity and superior performance over vancomycin in time-kill assays. It exhibited selective toxicity against bacterial cells, minimal cytotoxicity in human cell lines and low hemolytic activity. Mechanistic studies showed that compound 29 targets the bacterial cell wall by binding to penicillin-binding protein 2a (PBP2a), disrupting cell wall integrity. Additionally, it showed strong anti-biofilm activity and reduced MRSA biofilms by up to 40%. Preliminary pharmacokinetic profiles suggested a favorable profile, including a prolonged plasma half-life and good oral bioavailability. These results suggest that compound 29 is a promising lead for further development in the fight against MRSA.

Antimicrobial activity and cytotoxic and epigenetic effects of tannic acid-loaded chitosan nanoparticles

Tannic acid (TA) is a potent antitumor agent, but its low bioavailability and absorption limit its use. In this study, it was loaded into chitosan-based nanoparticles (Chi-NPs) to overcome these limitations and to improve its antimicrobial and anticancer activities. TA-loaded Chi-NPs (Chi-TA-NPs) were synthesized using the ionic gelation method and physicochemically characterized by FE-SEM, FTIR, XRD, PDI, DLS, and zeta potential analysis. Additionally, the antimicrobial activity of Chi-TA-NPs against two G+ bacterial strains, two G− bacterial strains, and a fungal strain (Candida albicans) was investigated using the microbroth dilution method. MTT assay was used to examine the cytotoxic effects of Chi-TA-NPs on HepG2 cells. The expression of DNA methyltransferase 1 (DNMT1), DNMT3A, and DNMT3B was examined in HepG2 cells using RT-qPCR. The amount of 5-methylcytosine in the HepG2 cell-derived genomic DNA was measured using ELISA. FE-SEM micrographs showed the loading of TA into the chitosan-based formulation. The peaks detected in the XRD and FTIR analyses confirmed the formation of the Chi-TA-NPs. The PDI value (0.247 ± 0.03), size (567.0 ± 25.84 nm), and zeta potential (17.0 ± 5.86 mV) confirmed the relative stability of Chi-TA-NPs. A constant release profile in line with the Korsmeyer-Peppas model was detected for Chi-TA-NPs, such that approximately 44% of TA was released after 300 min. In addition, Chi-TA-NPs exhibited effective antimicrobial activity against the studied microbial strains, as manifested by MIC values ranging from 250 to 1000 µg/mL. Chi-TA-NPs induced cytotoxicity in liver tumor cell line, with an IC50 value of 500 µg/mL. Furthermore, Chi-TA-NPs considerably decreased the expression of DNMT1 (2.52-fold; p = 0.01), DNMT3A (2.96-fold; p = 0.004), and DNMT3B (2.94-fold; p < 0.0001). However, 5-methylcytosine levels in HepG2 cells were unaffected by Chi-TA-NPs treatment (p = 0.62). Finally, the antimicrobial, cytotoxic, and epigenetic effects of Chi-TA-NPs were more pronounced than those of free TA and the unloaded Chi-NPs. In conclusion, Chi-TA-NPs exhibit promising potential for reducing microbial growth and promoting cytotoxicity in liver cancer cells.

Repurposing Osimertinib and Gedatolisib for Glioblastoma Treatment: Evidence of Synergistic Effects in an In Vitro Phenotypic Study.

Background/Objectives: Glioblastoma is a malignant tumor with a poor prognosis for the patient due to its high lethality and limited chemotherapy available. Therefore, from the point of view of chemotherapy treatment, glioblastoma can be considered an unmet medical need. This has led to the investigation of new drugs for monotherapy or associations, acting by synergistic pharmacological mechanisms. Methods: Here, we propose the combination of Osimertinib (a potent EGFR inhibitor) and Gedatolisib (a potent PI3K/mTOR dual inhibitor) through an in vitro phenotypic study using five human GB lines and establish the cytotoxic potency, selectivity, and effect on proliferation, apoptosis, and cell cycle by simultaneously inhibiting EGFR, PI3K, and mTOR. Results: Cytotoxic potency of Gedatolisib and Osimertinib in the selected GB cell lines was determined, which highlighted the synergistic response from their combination and its impact on migration reduction, G0/G1 cell cycle arrest, GB cytotoxicity, and apoptosis-inducing effects for different GB cell lines. Conclusions: From the drug combination studies in phenotypic in vitro models, it was possible to suggest a new potential treatment for glioblastoma that justifies further safe in vivo phases of preclinical trials with the combination.

Synthesis, modification, characterization, and in vitro evaluation of chitosan-hyaluronic acid coated MIL-100 (Fe) nanoparticles for methotrexate delivery in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation of the joints, leading to pain, swelling, and potential joint destruction. Effective management of RA is crucial to improve patients' quality of life and prevent long-term disability. Methotrexate (MTX) is a widely used disease-modifying antirheumatic drug (DMARD) that has shown efficacy in treating RA. However, its use is often limited by significant adverse effects, particularly on healthy tissues and organs, including hepatotoxicity, myelosuppression, and gastrointestinal complications. Therefore, developing targeted drug delivery systems (DDSs) for MTX is essential to enhance its therapeutic effects while minimizing systemic toxicity. Metal-organic frameworks (MOFs), specifically MIL-100(Fe), present a promising approach for targeted drug delivery in RA treatment due to their high porosity, large surface area, and excellent loading capacity. The acid-responsive properties of MIL-100(Fe) make it particularly suitable for targeting the acidic microenvironment of inflamed joints. In this study, we synthesized MIL-100(Fe) using a microwave-assisted method and embedded MTX within these nanocarriers. The nanocarriers were subsequently coated with chitosan and modified with hyaluronic acid through 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). Comprehensive characterization techniques such as dynamic light scattering (DLS), zeta potential analysis, Brunauer-Emmett-Teller (BET) surface area measurement, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and field emission scanning electron microscopy (FESEM) were employed to evaluate the nanoparticles. Additionally, we assessed cell cytotoxicity and cellular uptake in macrophage cell lines. Overall, the results indicate that the prepared MIL-100(Fe) nanoparticles are a suitable DDS for targeted MTX delivery in RA treatment.

An in vitro evaluation of the cytotoxic potential of medicinal mushrooms against human breast cancer cell lines.

Medicinal mushroom extracts, i.e. their dried biomass, have long been known as sources of bioactive compounds with positive effects on the human health. The antioxidant, antigenotoxic, antiviral, and immunomodulatory properties of the commercially available extracts Agaricus blazei auct. non Murrill (AB), Cordyceps sinensis (Berk.) Sacc. (CS), and Immune Assist (IA) have already been documented. This study, studied the influence of these three mushrooms on the viability of cell lines MCF-7, MDA-MB-231, and HS-5. The cytotoxicity of AB, CS, and IA at different concentrations (25, 50, 100, 200, 400 and 800 μg/mL) was evaluated using the MTT assay. The results showed that AB was the most effective and induced cytotoxicity in both cancer cell lines, with IC50 values of 96.7 μg/mL for MCF-7 and 368.4 μg/mL for MDA-MB-231. After treatment with CS and IA, the half-maximal inhibitory concentration was reached only in MDA- MB-231 cells (IC50=613 μg/mL for CS and 343.3 μg/mL for IA). We have shown here that AB, CS and IA can suppress the growth of MCF-7 and MDA-MB-231 cell lines, while affecting the survival of healthy HS-5 cells to a much lesser extent. Our in vitro results suggested that AB, CS and IA are promising natural sources with potential anticancer activity.

Effect of combination of polyphenols, polysaccharide, and sodium selenite on bortezomib anti-cancer action.

Combinatorial drug delivery has shown promising results over single drug for cancer therapy. Here, we aimed to explore combination of proteasome inhibitor; bortezomib (BTZ) with natural antioxidants (AOs); polyphenols like caffeic acid (CFA), resveratrol (RES), fucoidan (FD), and synthetic AO; sodium selenite (Na2SeO3) for cellular cytotoxicity in breast cancer cell lines; MCF-7 and MDA MB-231. The combination of RES + BTZ, FD + BTZ, and Na2SeO3 + BTZ showed synergism while CFA showed antagonism with BTZ. The EC50 values of different combinations were found to be significantly less than the individual AOs in ABTS and DPPH assay. Furthermore, the effect of combination of drugs on migratory properties of MCF-7 cells were evaluated by in-vitro wound healing assay, resulting in the reduction of such behavior. In support of this, RT-qPCR was performed to analyze differential gene expressions of apoptotic and Epithelial-Mesenchymal Transition (EMT) markers with and without treatment. In results, the combination of Na2SeO3 + BTZ reduced the expression of Bcl-XL and N-Cad causing cytotoxicity and suggested that the combination of Na2SeO3 + BTZ (IC50 = 1.40 ± 0.45 μM) could be a better option among other combinations for breast cancer therapy. Overall, the outcome indicates that the combination of BTZ with AOs may yield potential therapeutic benefit.