Cytotoxic Properties Research Articles

Lepidium peruvianum as a Source of Compounds with Anticancer and Cosmetic Applications

Lepidium peruvianum—an edible herbaceous biennial plant distributed in the Andes—has been used for centuries as food and as a natural medicine in treating hormonal disorders, as an antidepressant, and as an anti-osteoporotic agent. The presented study aims to prove its beneficial cosmetic and chemopreventive properties by testing the antiradical, whitening, cytotoxic, and anticancer properties of differently colored phenotypes that were extracted using three solvents: methanol, water, and chloroform, with the help of the chemometric approach to provide evidence on the impact of single glucosinolanes (seven identified compounds in the HPLC-ESI-QTOF-MS/MS analysis) on the biological activity of the total extracts. The tested extracts exhibited moderate antiradical activity, with the methanolic extract from yellow and grey maca phenotypes scavenging 49.9 ± 8.96% and 48.8% ± 0.44% of DPPH radical solution at a concentration of 1 mg/mL, respectively. Grey maca was the most active tyrosinase inhibitor, with 72.86 ± 3.42% of the enzyme activity calculated for the water extract and 75.66 ± 6.21% for the chloroform extract. The studies in cells showed no cytotoxicity towards the human keratinocyte line HaCaT in all studied extracts and a marked inhibition of cell viability towards the G361 melanoma cell line, which the presence of pent-4-enylglucosinolate, glucotropaeolin, and glucoalyssin in the samples could have caused. Given all biological activity tests combined, the three mentioned compounds were shown to be the most significant positive contributors to the results obtained, and the grey maca water extract was found to be the best source of the former compound among the tested samples.

Formulation of Curcumin-based Polyherbal Nanoemulsion Mouthwash and Assessment of its Antioxidant and in-vitro Cytotoxic Properties

Formulation of Curcumin-based Polyherbal Nanoemulsion Mouthwash and Assessment of its Antioxidant and in-vitro Cytotoxic Properties

Synthesis of a novel water-soluble pyridine dicarboxylate and its application in fluorescence cell imaging

Abstract A novel water-soluble substituted pyridine dicarboxylate containing a quaternary ammonium ion with potential applications in fluorescence cell imaging was synthesized and characterized. Remarkably, this compound exhibited water solubility in the absence of additional solubilizers, enabling direct dissolution in phosphate-buffered saline for cell studies. No obvious cytotoxicity was observed in 4T1 cells (mouse breast cancer cells) within the concentration range of 0.2–25 μmol L−1, with a cell survival rate above 89%. Furthermore, the compound exhibited a maximum two-photon absorption cross-section of 86 GM at an excitation wavelength of 780 nm, demonstrating high cell permeability, effective distribution in the cytoplasm, and preferential targeting of organelles. Single- and two-photon fluorescence imaging of cells revealed a distinctive blue emission and strong bright green emission, respectively. The newly synthesized substituted pyridine dicarboxylate exhibited low cytotoxicity and strong fluorescence imaging properties, demonstrating its potential in cell imaging applications.

A Comparative Study on the in vitro Cytotoxicity and Anti-Cancer Properties of Gold Nanoparticles Derived from Elettaria cardamomum

A Comparative Study on the in vitro Cytotoxicity and Anti-Cancer Properties of Gold Nanoparticles Derived from Elettaria cardamomum

Investigating the antioxidant properties and GC-MS profile of Indian native medicinal flower Pandanus odorifer and assessing its cytotoxic effects on HT-29 cells

This study aimed to investigate the antioxidant potential and bioactive compounds of Pandanus odorifer flower. The phytochemical investigation includes both qualitative and quantitative experiments. In vitro antioxidant studies were conducted using DPPH, ABTS and hydroxyl methods. The bioactive compounds present in the ethanol extract were identified using GC-MS analysis. The MTT assay was carried out on HT-29 colon cancer cells to investigate the cytotoxic ability of the ethanolic extract. The qualitative phytochemical analysis demonstrated the presence of flavonoids, phenolic compounds, tannins, saponins, steroids, carboxylic acids and cardiac glycosides. The determination of flavonoid showed 400 ± 0.110 mg/g and 250±0.090 mg/g of quercetin equivalent in ethanol and water extracts. Similarly, the determination of phenol exhibited 108±0.210 mg/g and 87±0.173 mg/g gallic acid equivalent in ethanol and water extracts. The total antioxidant capacity revealed 1.6 ± 0.093 mg/g and 1.3± 0.056 mg/g equivalent of ascorbic acid in ethanol and water extracts. The DPPH assay showed IC50 values of 35.06 µg/mL in ethanol and 44.82 µg/mL in water extract. Likewise, the ABTS assay revealed an IC50 value of 42.20 µg/mL and 47.45 µg/mL in ethanol and water extract. The hydroxyl radical assay showed IC50 value of 23.95 µg/mL in ethanol and 36.56 µg/mL in water extract. 22 bioactive compounds were identified using GC-MS analysis based on their similarity index. The ethanolic extract showed greater cytotoxic activity with the IC50 value of 28.08 µg/mL on HT-29 colon cancer cells. This study concludes that the Pandanus odorifer flower extracts exhibited significant antioxidant and cytotoxic property.

In-vitro scientific validation of anti-inflammatory activity of Punica granatum L. on Leukemia monocytic cell line

Background: The induction of the inflammatory cascade results in the production of a number of inflammatory mediators, including prostaglandin E2 (PGE2), nitric oxide (NO), and proinflammatory cytokines like TNF-, IL-, and IL-6. This study examined the cytotoxicity and anti-inflammatory properties of a methanolic crude extract of Punica granatum L. peel (PPM) on monocytic leukaemia cell line (THP-1). Materials and methods: The PPM along with Quercetin as reference was used to assess the cytotoxic effect on THP-1 cells and describe its effect on pro-inflammatory cytokines such as COX-2, TNF-α, IL-6 against cancer cell line by flow cytometry. Results: The percentage of viable cells significantly decreased which correlates to non-toxicity whereas quercetin was found to be highly toxic, the IC50 could not be calculated because of drug precipitation. There was a significant decrease in the expressions of inflammatory cytokines upon pre-treatment of the cells with PPM prior to LPS stimulation. Conclusion: Our findings indicate that no cytotoxicity was observed after the treatment of THP-1 cells with PPM (25-400 µg/ml), but at higher concentration (400µg/ml), the cell viability decreased to 84% and attenuated the expression level of inflammatory cytokines. The inhibitory effect of the extract on pro-inflammatory factors production may provide a theoretical source on upcoming treatment of inflammation. Keywords: Punica granatum L; Monocytic leukaemia cell line; cytotoxicity; anti-inflammation.

Synthesis, Antimicrobial - Cytotoxic Evaluation, and Molecular Docking Studies of Quinolin-2-one Hydrazones Containing Nitrophenyl or Isonicotinoyl/Nicotinoyl Moiety.

By applying the hybrid molecular strategy, in this study, we reported the synthesis of fifteen quinolin-2-one hydrazones containing nitrophenyl or nicotinonyl/isonicotinoyl moiety, followed by in vitro and in silico evaluations of their potential antimicrobial and anticancer activities. In vitro antimicrobial evaluation of the target compounds on seven pathogenic strains, applying the broth microdilution method, revealed that compound 4a demonstrated the most potential antifungal activity against C. albicans (MIC 512 μg mL-1) and C. krusei (MIC 128 μg mL-1). In vitro cytotoxic evaluation of the target compounds on three human cancer cell lines, employing the MTT method, suggested that compound 5c exhibited the most potential cytotoxicities against HepG2 (IC50 10.19 μM), A549 (IC50 20.43 μM), and MDA-MB-231 (IC50 16.82 μM) cells. Additionally, molecular docking studies were performed to investigate the binding characteristics of compounds 4a and 5c with fungal lanosterol 14α-demethylase and human topoisomerase I-II, respectively, thereby contributing to the elucidation of their in vitro antifungal and cytotoxic properties. Furthermore, compounds 4a and 5c, via SwissADME prediction, could exhibit favorable physicochemical and pharmacokinetic properties. In conclusion, this study provides valuable insights into the potential of quinolin-2-one hydrazones as promising candidates for the development of novel antimicrobial and anticancer agents in the future.

Targeted immune cell therapy for hepatocellular carcinoma using expanded liver mononuclear cell-derived natural killer cells

Natural killer (NK) cells are a promising cellular therapy for T cell-refractory cancers but are frequently deficient or dysfunctional in patients with hepatocellular carcinoma (HCC). In the present study, we explored a novel therapy for HCC using NK cells derived from donor liver graft perfusate. These liver-derived NK cells, named LMNC-NK cells, are more abundant in liver mononuclear cells (LMNCs) than in peripheral blood mononuclear cells (PBMCs) from the same donor. We developed a method to expand LMNC-NK cells by 33.8±54.4-fold, enhancing their cytotoxic properties and cytokine production, including granzyme B, CD107a, TNF-α, and IFN-γ. These cells also showed an increased expression of cytotoxicity receptors. An RNA-seq analysis revealed considerable differences in gene expression between LMNC-NK and PBMC-NK cells, with 453 genes upregulated and 449 downregulated in LMNC-NK cells. These genes are involved in the mitogen-activated protein kinase cascade and cell differentiation, explaining the increased activity of LMNC-NK cells. Quantitative reverse transcription polymerase chain reaction confirmed the significant upregulation of TLR6, KIT, MMP14, IRF8, TCF7, FCERIG, LEF1, NLRp3, and IL16 in LMNC-NK cells. LMNC-NK cells effectively eliminated HepG-2-Luc cells in vitro, and in an orthotopic murine model of HCC, they exhibited a potent anti-tumor effect, outperforming PBMC-NK cells. The expression of the activation marker CD69+ in LMNC-NK cells was also significantly higher among tumor-infiltrating lymphocytes compared to PBMC-NK cells. Our research suggests that the adoptive transfer of LMNC-NK cells could be a promising treatment for HCC, offering a novel and effective source of NK cells with superior cytotoxic functions.

Synergistic Effects of Psidium Guajava and Copper Nanoparticles Reinforced Hybrid Hydrogel for Tissue Engineering

Hydrogels are biopolymers proficient in engrossing much water in their 3D network structure. However, single-polymer hydrogels frequently experience poor physio-mechanical properties, confining their border applications. The present work concentrated on developing chemically crosslinked hydrogels using the terpolymerization of gelatin (GEL), guar gum (GGM), and polyvinyl alcohol (PVA). Ethanolic extract of Psidium guajava leaf (EPG) and copper nanoparticles (CuNPs) were added to enhance the biomechanical properties of the developed hydrogels. Hydrogels' viscoelastic, mechanical, swelling, and cytotoxicity properties were assessed. All the hydrogels exhibited a porous-like structure with a swelling index of 230 to 280%. A compressive strength of 5 MPa with splendid chondrocyte viability was noticed in the hydrogels comprised of EPG and CuNPs. The multiple interactions among the polymer chains impart better frequency and shear strain-dependent behavior. The time-dependent frictional behavior of hydrogel under the lubrication of artificial synovial fluid reveals the decreased coefficient of friction over time. The performance of the hybrid hydrogel enhanced with EPG and CuNPs was superior, making it a promising material for tissue engineering applications.

Synthesis of Thiazole‐Fused Diosgenin Derivatives as Potential Therapeutic Agents

AbstractDiosgenin, a hydrolyzed product of phytosteroid saponin, has widely been studied for its medicinal properties. In an effort to find bioactive molecules, 25 novel thiazole‐fused diosgenin molecules have been synthesized by an efficient reaction protocol. The chemistry involves the Oppenauer oxidation followed by double bond isomerization in a one‐pot reaction, epoxidation, and the reaction of urea derivatives with the epoxyketone to synthesize the target compounds. These novel chimeric compounds were tested for their potential antimicrobial and cytotoxic properties. Antimicrobial studies against a panel of Gram‐positive and Gram‐negative led to the discovery of some of these molecules as narrow‐spectrum antimicrobial agents against Bacillus subtilis bacteria. In preliminary cytotoxicity studies, 2‐fluorophenyl derivative (10) inhibited the growth of several cell lines of the NCI‐60 cell line panels including >93 % inhibition of UO‐31 cell line. Furthermore, the hit antibacterial compounds are non‐toxic to human cancer cell lines, and the cytotoxic compound is not active against the bacterial strains, showing the selective therapeutic potential of the chimeric compounds.

Evaluation of high-value bioproducts production by marine endophytic fungus Arthrinium sp. FAKSA 10 under solid state fermentation using agro-industrial wastes

BackgroundTo address public health challenges, there is increasing interest in bioactive metabolites from unconventional sources for targeted cancer and viral treatments with minimal side effects. Endophytic fungi are promising for these therapies. This study focused on maximizing bioactive agent yields from these fungi using a low-cost medium and optimized fermentation system. ResultsForty-three endophytic fungi isolated from Sinularia polydactyla were cultivated on wheat bran medium and evaluated for bioactive metabolites under solid-state fermentation. Strain FAKSA 10, identified as Arthrinium sp. FAKSA 10, exhibited the highest levels of pharmaceutical metabolites, including L-glutaminase, L-methioninase, L-arginase, L-asparaginase, L-tyrosinase, L-lysine α-oxidase, and ribonuclease, with a 79.12% hepatitis C virus knockdown rate. This strain produced 46 metabolites with anticancer, antioxidant, antiviral, and cytotoxic properties, including major compounds like hexadecanoic acid methyl ester; hexadecanoic acid ethyl ester; 9, 12-octadecadienoic acid (Z, Z), methyl ester; 9-octadecenoic acid (Z)-, methyl ester, and 11, 14-eicosadienoic acid, methyl ester. A cost effective strategy using 11 agro-industrial residues was applied, following by optimization of the solid-state fermentation system. This optimization increased enzyme yields and enhanced antiviral and antioxidant activities. The optimal conditions for solid-state fermentation were a 10 d incubation, 1 mm particle size, 60% initial moisture, 28°C temperature, and 2 × 107 CFU/mL inoculum size. ConclusionsThis study exploited Arthrinium sp. FAKSA 10 metabolites as natural pharmaceuticals against cancer and viral diseases, highlighting their significant antioxidant properties. Among various residues, oil cakes emerged as an effective and cost-efficient medium, capable of significantly enhancing the production of valuable bioactive metabolites.

Polyphenol Treatment of Peripheral Blood Mononuclear Cells from Individuals of Different Ages.

Human peripheral blood mononuclear cells (PBMCs) have been largely utilized to assess the cytotoxic, immunomodulatory, and anti-inflammatory properties of both synthetic and natural compounds. Within the latter category, polyphenols from dietary sources have been extensively analyzed. PBMCs represent a feasible in vitro model to study polyphenol hallmarks and activity according to quantitative and qualitative differences in immune responses in individuals of different age. In this chapter, we propose a method for PBMC treatment with polyphenols and analysis designed on age-dependent qualitative and quantitative variability in immune cell performance.

In vitro bio-activity of Rosa rubiginosa L. (sweet briar) rosehip fixed oil combined with essential oils for acne vulgaris

Cutibacterium acnes, Staphylococcus epidermidis, and Staphylococcus aureus proliferate within accumulated sebum and produce localised inflammation thereby inducing acne vulgaris. Essential oils are one of the leading natural products used for acne and are diluted in fixed oils to reduce irritation and toxicity. This study investigated the in vitro antimicrobial, anti-inflammatory, cytotoxicity, and skin retention properties of Rosa rubiginosa rosehip fixed oil in combination with essential oils having activity against acne vulgaris. The broth microdilution assay was used to determine the minimum inhibitory concentration (MIC), and the sum of the fractional inhibitory concentration index (ΣFIC) was calculated for the interactions. The lipopolysaccharide (LPS) induced inflammatory pathway in RAW 264.7 macrophages was used to assess anti-inflammatory activity. A dual-staining method in A549 epithelial cells was used to assess cytotoxicity. Qualitative Fourier Transform Infrared spectroscopy analysis was used for initial skin retention determination. Rosa rubiginosa oil combined with Cinnamomum zeylanicum essential oil displayed antimicrobial synergy (MIC = 0.42 mg/ mL; ΣFIC = 0.45) against three acne-inducing strains. Rosa rubiginosa fixed oil combined with Styrax benzoin essential oil suppressed LPS-induced nitrite production by 33.80%. Rosa rubiginosa oil combined with Melaleuca quinquenervia essential oil exhibited the lowest cytotoxicity (84.32% cell viability). Rosa rubiginosa oil combined with either C. zeylanicum, Eugenia caryophyllata, Rosa damascena or S. benzoin essential oil was retained within the porcine skin. Rosa rubiginosa fixed oil serves as an ideal carrier oil that can potentiate selected essential oils for the treatment of acne vulgaris.

Effect of Zr dopant on in vitro cytotoxicity and neurogenic property of spray-dried bioactive glass microspheres

Bioactive glasses (BGs) have been extensively applied in dental and tissue engineering fields due to their bioactivity, biocompatibility, and degradability. Despite the advantages, the material itself lacks functionalities such as angiogenesis and antibacterial properties which could limit its applications. To address this, trace elements like copper (Cu), manganese (Mn), boron (B), and zinc (Zn) have been incorporated to enhance their therapeutic applications. Further, to explore the potential of neurogenic applications, this study fabricated both spray-dried undoped and Zr-doped BG specimens, which were then characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier-transform infrared spectroscopy (FTIR). The in vitro bioactivity was assessed with simulated body fluid (SBF), cytotoxicity with L929 fibroblast cells, and neurogenic properties via the neuronal marker Tuj1+. Finally, the study discusses the particle formation mechanism and their in vitro biological properties, aiming to enhance the understanding of BGs in neurogenesis.

Phytochemical Screening, Antioxidant, Cytotoxic, Analgesic, Antidiarrheal Activity and GC-MS Analysis of the Leaves of Stachyphrynium Placentarium

The goal of the present study is to analyze the phytochemicals, antioxidants, cytotoxic, analgesic and anti-diarrheal properties of the leaves of Stachyphrynium placentarium methanol extract as well as its dichloromethane soluble fraction using GC-MS technique. The leaves of the S. placentarium were extracted with methanol and designated as SPM. Phytochemicals investigation exhibited the presence of several important secondary metabolites. Antioxidants such as total phenolic content, flavonoids content, total antioxidant, reducing power capacity and DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging assay SPM revealed non-significant antioxidant properties. The cytotoxicity study of the extract showed significant cytotoxicity (LC50 35.1093 µg/mL) compared to standard vincristine sulfate (LC50 0.482 µg/mL). Analgesic study of S. placentarium by hot plate model indicates both the doses exhibited significant central analgesic activity compared with the control. The maximum analgesic activity was observed at 90 min. SPM (500 mg/kg) is 60.21 %. SPM250 also showed a significant percentage of elongation or latency from 30 to 150 min 57.00, 59.64, 59.88, 58.07 and 53.71 %, respectively 30 min time interval. In the acetic acid writhing test, S. placentarium significantly outperformed the control and standard (SPM250 - 52.27 %, SPM500 - 34.09 and STD - 27.27 %), showing a significant increase in peripheral analgesic activity (p < 0.001). Antidiarrheal activity of SPM showed that SPM250 and SPM500 substantially decreased the feces in castor oil-induced diarrhea (p < 0.05). According to the study, the incidence and severity of diarrhea are significantly reduced by SPM500. Four chemicals are found in the dichloromethane-soluble portion of the methanol extract of S. placentarium leaves, according to GC-MS studies such as Octadecane, 6-methyl- (1.326 %), Dodecane (1.02 %), 1-Iodo-2-methylundecane (0.47 %), tetradecanoic acid 12-methyl, methyl ester (72.64 %). Tetradecanoic acid exhibits anti-inflammatory, anticancer, 5-reductase inhibitory, antioxidant, hemolytic and antifibrinolytic properties. HIGHLIGHTS The phytochemicals, antioxidants, cytotoxic, analgesic and anti-diarrheal properties of Stachyphrynium placentarium methanol extract (SPM) leaves. The dichloromethane soluble fraction is examined using Gas chromatography–mass spectrometry (GC-MS) and identified Octadecane, 6-methyl-, Dodecane, 1-Iodo-2-methylundecane, tetradecanoic acid 12-methyl, methyl ester. The brine shrimp lethality test exhibited that SPM has significant cytotoxicity (LC50 35.1093 µg/mL) compared to vincristine sulphate (LC50 0.482µg/mL), the extract showed significant cytotoxicity (LC50 35.1093 µg/mL). S. placentarium at both dosages (250 and 500 mg) provided significant central analgesia compared to the control in a hot plate model. In the acetic acid writhing test, S. placentarium showed significantly higher peripheral analgesic action (SPM250 - 52.27, SPM500 - 34.09 and STD - 27.27 %) compared to control and standard. In castor oil-induced diarrhoea, SPM250 and SPM500 (250 and 500 mg) showed significantly reduced faeces production (p < 0.05). GRAPHICAL ABSTRACT

Development of multi-herbal formulation with enhanced antimicrobial, antioxidant, cytotoxic, and antiaging properties

We developed a multi-herbal formulation (MCCSSTAMP) containing Mentha piperita, Allium sativum, Syzygium aromaticum, Curcuma longa, Syzygium cumini, Trigonella foenum-graecum, Coriandrum sativum, Murraya koenigii and Piper nigrum which was found to be versatile for the development of novel medicines and cosmetic products. The formulation was prepared using a hydro-alcoholic base and its phytochemical composition was analyzed. The initial phytochemical analysis revealed that MCCSSTAMP contained various phytochemicals, with the highest concentrations of phenolic content. The antimicrobial, anti-oxidant, cytotoxic, and anti-aging properties of the MCCSSTAMP were explored. The formulation showed potent anti-microbial efficacy against various microorganisms, including antibiotic-resistant strains. MCCSSTAMP also demonstrated potent anti-oxidant activity, effectively scavenging free radicals and chelating metal ions. Furthermore, it exhibited cytotoxic activity against carcinoma cell lines, comparable to a standard chemotherapeutic agent cisplatin. The formulation has a potential anti-aging agent and skin-whitening additive due to its significant inhibitory activity against enzymes involved in the aging process, such as hyaluronidase, elastase, and tyrosinase. Our study claims that the efficacy was attributed to the synergistic effect of combining multiple herbs in the formulation. Further, it acted as a viable source of nutritional supplements for the nutraceutical industry, as all of the plants used in the formulation are edible, making it a promising candidate for cancer treatment research and its application in cosmetic products to address hyperpigmentation and maintain skin integrity.

Amcasertib Increases Apoptosis While Decreasing Invasive and Migrating Abilities in Breast Cancer Stem Cells

Objective: A relationship exists between breast cancer stem cells (BCSCs) and the chemo-resistance and recurrence of aggressive breast tumors. Amcasertib is a small chemical compound and multiple kinase inhibitor that inhibits downstream Nanog and other cancer stem signaling pathways in cancer stem cells by targeting several serine-threonine kinases. In this study, we aimed to investigate the cytotoxicity and anticancer effects of Amcasertib on BCSCs, gaining insight into the targetability of BCSCs. Method: We used the combined xCELLigence-Real-Time Cell Analyzer (RTCA) equipment to analyze cytotoxicity and cell proliferation. We detected the IC50 dosages of Amcasertib at 24, 48, and 72 hours and examined its effects on apoptosis, cell cycle, invasion, and migration over 48 hours. We used flow cytometry for assays of apoptosis and cell cycle, and the CytoSelect 96-well Cell Migration and Invasion Assay Kit for evaluating invasion and migration. Results: Our results showed that Amcasertib has cytotoxic properties, with an IC50 dosage of 1.9 μM at the 48th hour. In addition, Amcasertib significantly induced apoptosis in BCSCs, despite not affecting the cell cycle. Moreover, Amcasertib decreased BCSCs’ invasion and migratory properties, part of epithelial-mesenchymal transition (EMT). Conclusion: In conclusion, our findings provide crucial information for understanding the potential of Amcasertib in targeting BCSCs. In addition, we suggest that Amcasertib could be a beneficial drug for breast cancer treatment by targeting BCSCs.

The Yin and Yang of the Natural Product Triptolide and Its Interactions with XPB, an Essential Protein for Gene Expression and DNA Repair.

Triptolide, a bioactive diterpene tri-epoxide extracted from Tripterygium wilfordii Hook F (TWHF), exhibits notable pharmacological activities, including anti-inflammatory, immunosuppressive, antifertility, and anticancer effects. Despite its promising therapeutic potential, clinical applications of triptolide are significantly limited by its poor water solubility and substantial toxicity, particularly hepatotoxicity, nephrotoxicity, and cardiotoxicity. These toxic effects are difficult to separate from many of its desired therapeutic effects, the Yin and Yang of triptolide applications. Triptolide's therapeutic and toxic effects are linked to its inhibitory interactions with XPB, a DNA helicase essential for transcription by RNA polymerase II (RNAPII) and nucleotide excision repair (NER). By irreversibly binding to XPB, triptolide inhibits its ATPase activity, leading to global repression of transcription and impaired NER, which underlies its cytotoxic and antitumor properties. Recent developments, including triptolide prodrugs such as Minnelide and derivatives like glutriptolides, aim to enhance its pharmacokinetic properties and reduce toxicity. This review critically examines triptolide's chemical structure, therapeutic applications, toxicological profile, and molecular interactions with XPB and other protein targets to inform future strategies that maximize therapeutic efficacy while minimizing adverse effects.

Thiolated layered double hydroxide-based nanoparticles: A study on mucoadhesiveness and cytotoxicity

The aim of this study was the synthesis and characterization of thiolated Mg/Al Layered double hydroxide nanoparticles (nLDH) that can adhere to mucosal surfaces. For this purpose, initially, nLDH were synthesized and then their surface was modified with L-cysteine (Cys). Then the Cys-modified nanoparticle structure (nLDHCys) was characterized by FTIR, XRD and FE-SEM/EDS, and the amount of thiol groups was determined using the iodometric method. The cytotoxicity properties of nLDH and LDHCys were examined on cervical (HeLa), fibroblast (L929) and colon (HT29) cell lines. In addition, the adhesion of nanoparticles to mucosal surfaces has been evaluated through mucin interaction experiments and ex vivo tests on ewe vaginal tissue. The results from characterization studies prove that Cys molecule has been successfully modified on the surface of nLDH. Cytotoxicity studies demonstrated that Cys modification did not negatively affect the cell viability, and these results were extremely close to those of nLDH. Ex vivo tests on ewe vaginal tissue and mucin interaction demonstrated that nLDHCys enhanced retention on the mucosal surface. Considering their retention ability to mucosal surface and their biocompatible nature, nLDHCys is expected to play an important role as a promising option for a safe mucoadhesive nanoparticle system for biological applications in the future.

Preparation and Biochemical Activity of Copper-Coated Cellulose Nonwoven Fabric via Magnetron Sputtering and Alginate-Calcium Ion Complexation.

Alginate-based materials have gained significant recognition in the medical industry due to their favorable biochemical properties. As a continuation of our previous studies, we have introduced a new composite consisting of cellulose nonwoven fabric charged with a metallic copper core (CNW-Cu0) covered with a calcium alginate (ALG-Ca2+) layer. The preparation process for these materials involved three main steps: coating the cellulose nonwoven fabric with copper via magnetron sputtering (CNW → CNW-Cu0), subsequent deposition with sodium alginate (CNW-Cu0 → CNW-Cu0/ALG-Na+), followed by cross-linking the alginate chains with calcium ions (CNW-Cu0/ALG-Na+ → CNW-Cu0/ALG-Ca2+). The primary objective of the work was to supply these composites with such biological attributes as antibacterial and hemostatic activity. Namely, equipping the antibacterial materials (copper action on representative Gram-positive and Gram-negative bacteria and fungal strains) with induction of blood plasma clotting processes (activated partial thromboplastin time (aPTT) and prothrombin time (PT)). We determined the effect of CNW-Cu0/ALG-Ca2+ materials on the viability of Peripheral blood mononuclear (PBM) cells. Moreover, we studied the interactions of CNW-Cu0/ALG-Ca2+ materials with DNA using the relaxation plasmid assay. However, results showed CNW-Cu0/ALG-Ca2+'s cytotoxic properties against PBM cells in a time-dependent manner. Furthermore, the CNW-Cu0/ALG-Ca2+ composite exhibited the potential to interact directly with DNA. The results demonstrated that the CNW-Cu0/ALG-Ca2+ composites synthesized show promising potential for wound dressing applications.