Cytotoxicity Experiments Research Articles

Exploration of Aflatoxin B1 Degradation Products via Kocuria rosea: Structure Elucidation and Toxicity Analysis

Aflatoxin B1, a natural mycotoxin produced by Aspergillus fungi with high toxicity and carcinogenicity to humans and animals, has attracted more and more attention in the past 40 years. In the study of the biological detoxification of aflatoxin B1—although it has been confirmed that Kocuria rosea has the ability to efficiently remove aflatoxin B1—the degradation products, degradation pathways, and toxicity of the degradation products of aflatoxin B1 have not been clarified. Therefore, in this study, it was found that the functional groups of aflatoxin B1 changed after being cultured with Kocuria rosea, indicating the production of aflatoxin B1 degradation products. Ten main AFB1 degradation products (including aflatoxicol, aflatoxin D1, and aflatoxin D2) were identified, and their structures and fragmentation mechanisms were further elucidated by the parent ions and fragment ions of the products. The possible degradation pathway of aflatoxin B1 was proposed according to the structure of the degradation products. Additionally, the toxicity of the degradation products was analyzed according to the quantitative structure–activity relationship theory, and cytotoxicity experiments and dead–live cell staining experiments showed that the toxicity of the degradation products was significantly less than that of aflatoxin B1. In this study, the mechanism of aflatoxin B1 degradation by Kocuria rosea was explored from several perspectives, indicating that aflatoxin B1 degradation by Kocuria rosea is a promising biological method.

Substituent-Modulated Excited Triplet States and Activities of Ruthenium Complexes for Dual Photodynamic/Sonodynamic Therapy to Cisplatin-Resistant Non-Small Cell Lung Cancer.

Six polypyridyl Ru(II) complexes were designed for single-molecule photodynamic and sonodynamic therapy (PDT/SDT) synergistic multimodal anticancer toward cisplatin-resistant NSCLC. They demonstrated lowest 3ES with distinct intraligand transition nature, which is beneficial for singlet oxygen generation. Remarkable quantum yields of both singlet oxygen and superoxide anion under either 808 nm laser irradiation or ultrasonic treatment and could induce apoptosis and ferroptosis of A549R cells. Cytotoxicity experiments clearly demonstrated a synergistic effect between PDT and SDT. The relationship between the structures of these complexes and their cellular biological mechanisms has been explored in detail. Using a single-molecule sensitizer to achieve synergistic PDT/SDT may provide valuable insights for the treatment of drug-resistant tumors that located deeply and in hypoxic microenvironment.

Design of optimal concentrations for in vitro cytotoxicity experiments.

Concentration-dependent cytotoxicity experiments are frequently used in toxicology. Although it has been reported that an adequate choice of concentrations improves the quality of the statistical inference substantially, a recent literature review of three major toxicological journals has shown that the corresponding methods are rarely used in toxicological practice. In this study the performance of different sets of concentrations, also called designs, are analyzed, while the overall goal is to promote the advantages of optimal design procedures and to present a user-friendly guideline for planning new cytotoxicity concentration-response experiments. We compare the frequently used log-equidistant design to a Bayesian design, which is constructed by methods of optimum design theory. Using both a dense data set of concentration-cytotoxicity data of valproic acid (VPA) and regular assay data of 104 substances, the performance of the different designs is analyzed in two scenarios, where detailed previous knowledge on VPA is available or not. The results show that it is critical to apply a specific design strategy to determine optimal concentrations for cytotoxicity testing. In particular, the Bayesian design technique with and without incorporating pre-existing knowledge of a specific test substance resulted in a more precise statistical inference than the other used designs. Finally, we present a guideline for upcoming experiments and an accessible user-friendly Shiny app (see http://shiny.statistik.tu-dortmund.de:8080/app/occe ).

The antioxidant and cytotoxicity capabilities of the total methanol leaf extract of Camellia yokdonensis

Camellia yokdonensis was first described in 2006 and clarified as a Vietnamese endemic Camellia. Camellia species are often associated with strong biological activity and have high application potential. However, there is currently no research on the biological activity of C. yokdonensis. The experiment was performed using DPPH assay and PFRAP assay to investigate the antioxidant capacity of the leaf extract. Besides, a 72-hour cytotoxic assay experiment on cancer cells showed the toxicity of the extract. The results showed that C. yokdonensis leaf extract has the ability to reduce iron ions and scavenge DPPH free radicals with an EC50 of 19.37 ± 1.66 µg/mL. Anticancer activity was determined by IC50 values (µg/mL) on HCC-J5, A549, MCF-7, and K562 cells as 138.00 ± 11.60, 172.90 ± 22.31, 175.52 ± 16.70, and 48.82 ±12.59, respectively.

Ginger vesicle as a nanocarrier to deliver 10-hydroxycamptothecin

In this study, we developed the ginger vesicles as nanocarrier for the targeted delivery of 10-hydroxy-camptothecin (HCPT), aiming to improve its therapeutic efficacy while minimizing the systemic toxicity. Ginger vesicles exhibit a wide spectrum of biological activities and excellent biocompatibility, rendering them as the promising nanocarriers candidates for anticancer drug delivery. The ginger vesicles with an average diameter of 86.83 nm were successfully prepared by utilizing a gradient centrifugation method. The loading conditions for HCPT into the ginger vesicles were optimized through the addition of an appropriate amount of Ca2+. The loading efficiency, size distribution, stability, and cytotoxicity profile of the ginger vesicles were comprehensively characterized using UV spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS), and cytotoxicity experiments. Furthermore, in vitro cytotoxicity studies confirmed that ginger vesicles loaded with HCPT exhibited high inhibitory activity against tumor cells as evidenced by fluorescence imaging and flow cytometry analysis. Most importantly, in vivo antitumor assay demonstrated that the ginger vesicles loaded with HCPT displayed remarkable inhibitory effects on tumor growth. In summary, our results demonstrated the potential application of the ginger vesicles as ideal nanocarriers for delivering HCPT.

HDAC6 as a Prognostic Factor and Druggable Target in HER2-Positive Breast Cancer.

Adjuvant trastuzumab is the standard of care for HER2+ breast cancer (BC) patients. However, >50% of patients become resistant. This study aimed at the identification of the molecular factors associated with disease relapse and their further investigation as therapeutically exploitable targets. Analyses were conducted on formalin-fixed paraffin-embedded tissues of the primary tumors of relapsed (cases) and not relapsed (controls) HER2+ BC patients treated with adjuvant trastuzumab. The nCounter Human Breast Cancer Panel 360 was used. Logistic regression and partitioning around medoids were employed to identify the genes associated with disease recurrence. Cytotoxicity experiments using trastuzumab-resistant cell lines and a network pharmacology approach were carried out to investigate drug efficacy. A total of 52 patients (26 relapsed and 26 not relapsed) were analyzed. We found that a higher expression of HDAC6 was significantly associated with an increased risk of recurrence, with an adjusted OR of 3.20 (95% CI 1.38-9.91, p = 0.016). Then, we investigated the cytotoxic activity of the selective HDAC6 inhibitor Nexturastat A (NextA) on HER2+ cell lines, which were both sensitive and trastuzumab-resistant. A sub-cytotoxic concentration of NextA, combined with trastuzumab, showed a synergistic effect on BC cell lines. Finally, using a network pharmacology approach, we identified HSP90AA1 as the putative molecular candidate responsible for the synergism observed in vitro. Our findings encourage the exploration of the role of HDAC6 as a prognostic factor and the combinatorial use of HDAC6 selective inhibitors combined with trastuzumab in HER2+ BC, in particular for those patients experiencing drug resistance.

Biocompatible dipeptide coated on Pt/PEDOT:PSS modified silicon probes for tissues rejection alleviation

The implantable neural probe is an indispensable tool to record the high-quality spike signals. However, the high interface impedance of electrode-tissue and severe tissue rejection degrade the signal quality and shorten the service life of neural probes in-vivo. Here, a Pt/PEDOT:PSS modified silicon probes with biocompatible dipeptide layer is proposed to avoid these issues. First, a bilayer Pt/PEDOT:PSS was electrochemically deposited on gold microelectrodes to reduce the impedance. Then, a layer of dipeptide was deposited on the modified probe by physical vapor deposition (PVD) to mitigate tissue rejection. The electrochemical results show that the electrode-tissue interface impedance can be reduced by two orders of magnitude by the Pt/PEDOT:PSS modification, with negligible impedance variation by the following dipeptide layer. From the in-vitro accelerated aging, it can be inferred that the Pt/PEDOT:PSS/dipeptide modified microelectrodes can survive for more than 10 weeks. In-vitro cytotoxicity experiments show that the dipeptide can help improve the biocompatibility. Lastly, in-vivo implantation further proves that dipeptide may contribute to the realization of lower tissues rejection and higher signal-to-noise ratio within 8 weeks of implantation. The widely used silicon neural probes with the Pt/PEDOT:PSS modification and overall dipeptide coating provide as a new solution for long-term biocompatibility and high-quality neural signals.

Percutaneous Delivery of Oncogel for Targeted Liver Tumor Ablation and Controlled Release of Therapeutics.

Advanced-stage liver cancers are associated with poor prognosis and have limited treatment options, often leading the patient to hospice care. Percutaneous intratumoral injection of anticancer agents has emerged as a potential alternative to systemic therapy to overcome tumor barriers, increase bioavailability, potentiate immunotherapy, and avoid systemic toxicity, which advanced-stage cancer patients cannot tolerate. Here, an injectable OncoGel (OG) comprising of a nanocomposite hydrogel loaded with an ionic liquid (IL) is developed for achieving a predictable and uniform tumor ablation and long-term slow release of anticancer agents into the ablation zone. Rigorous mechanical, physiochemical, drug release, cytotoxicity experiments, and ex vivo human tissue testing identify an injectable version of the OG with bactericidal properties against highly resistant bacteria. Intratumoral injection of OG loaded with Nivolumab (Nivo) and doxorubicin (Dox) into highly malignant tumor models in mice, rats, and rabbits demonstrates enhanced survival and tumor regression associated with robust tissue ablation and drug distribution throughout the tumor. Mass cytometry and proteomic studies in a mouse model of colorectal cancer that often metastasizes to the liver indicate an enhanced anticancer immune response following the intratumoral injection of OG. OG may augment immunotherapy and potentially improve outcomes in liver cancer patients.

The characterization of BCL-xL displays a non-apoptotic role in suppression of NLRP1 inflammasome assembly in common carp (Cyprinus carpio L.)

The NLRP1 inflammasome is a crucial muti-protein complex in the host anti-pathogen immune response. The previous studies have revealed that the anti-apoptotic protein BCL-xL played a non-apoptotic role by impeding the activation of NLRP1 inflammasome in mammals. However, the potential role of BCL-xL in regulating the inflammasome in fish remains unclear. In the present study, the BCL-xL (CcBCL-xL) was cloned from the head kidney of common carp (Cyprinus carpio L.), and its regulatory effect on the NLRP1 inflammasome was explored. It was found that CcBCL-xL predominantly localized in the brain, spleen and head kidney of common carp, and upon stimulation with Aeromonas hydrophila (A. hydrophila), Edwardsiella tarda (E. tarda), or spring viremia of carp virus (SVCV), the expression of CcBCL-xL significantly increased in multiple immune organs. The interaction between CcBCL-xL and CcNLRP1 was confirmed by co-immunoprecipitation and immunofluorescence. Meanwhile, we also found that CcBCL-xL significantly inhibited the assembly of the CcNLRP1 inflammasome, through ASC oligomerization, ASC specks formation and cytotoxicity experiments. Furthermore, our results revealed that CcBCL-xL interacted with the NACHT, LRR, FIIND, and CARD domains of CcNLRP1. Taken together, the results provide a theoretical foundation for further exploring the regulatory mechanism of NLRP1, and for the prevention and treatment of infectious diseases in fish.

LILRB4 represents a promising target for immunotherapy by dual targeting tumor cells and myeloid-derived suppressive cells in multiple myeloma.

Multiple myeloma (MM) remains an incurable hematologic malignancy. Despite tremendous advances in the treatment of this disease, about 10% of patients still have very poor outcomes with a median overall survival of less than 24 months. Our study aimed to underscore the critical mechanisms pertaining to rapid disease progression and provide novel therapeutic choices for these ultrahigh-risk patients. We utilized single-cell transcriptomic sequencing to dissect the characteristic bone marrow niche of patients who survived less than 2 years (EM24). Notably, enrichment of a LILRB4high pre-mature plasma-cell cluster was observed in EM24 patients compared to patients with durable remission. This cluster exhibited aggressive proliferation and a drug-resistance phenotype. High levels of LILRB4 promoted MM clonogenicity and progression. Clinically, high expression of LILRB4 was correlated with poor prognosis in both newly diagnosed MM patients and relapsed/ refractory MM patients. ATAC-sequencing analysis identified that pronounced chromosomal accessibility caused the elevation of LILRB4 on MM cells. CRISPR-Cas9 deletion of LILRB4 alleviated the growth of MM cells, inhibited the immunosuppressive function of myeloid-derived suppressive cells (MDSC), and further rescued T-cell dysfunction in the MM microenvironment. Greater infiltration of MDSC was observed in EM24 patients. We therefore generated an innovative T-cell receptor-based chimeric antigen receptor T cell, LILRB4-STAR-T. Cytotoxicity experiments demonstrated that LILRB4-STAR-T cells efficaciously eliminated tumor cells and impeded MDSC function. In conclusion, our study elucidates that LILRB4 is an ideal biomarker and promising immunotherapy target for high-risk MM. LILRB4-STAR-T-cell immunotherapy is promising against both tumor cells and the immunosuppressive tumor microenvironment in MM.

Folic Acid‐Mediated Reduction‐Sensitive Curcumin Prodrug Enhances the Delivery Performance of Curcumin in Liver Cancer Cells

AbstractIn order to improve the delivery performance of curcumin (CUR) in liver cancer cells, we prepared a targeted and reduction‐sensitive prodrug, folic acid‐polyethylene glycol‐disulfide bond‐curcumin (FA‐PEG‐SS‐CUR). The synthesis involved the conjugation of CUR with NH2‐PEG‐NH2 through a disulfide bond, followed by the connection of CUR‐SS‐PEG‐NH2 to FA‐COOH via acylation. The resultant FA‐PEG‐SS‐CUR prodrug self‐assembled into nano micelles in aqueous solutions, displaying excellent dispersibility with an approximate particle size of 119 nm. In vitro drug release studies demonstrated the sensitivity of FA‐PEG‐SS‐CUR to glutathione (GSH), displaying sustained release performance. After 72 h, FA‐PEG‐SS‐CUR exhibited a drug release rate of 38% at low GSH concentration and 59% at high GSH concentration. Notably, FA‐PEG‐SS‐CUR micelles exhibited favorable biocompatibility. The hemolysis rate resulting from co‐incubation with red blood cells remained below 3%. Furthermore, cytotoxicity experiments unveiled the substantial cytotoxicity of FA‐PEG‐SS‐CUR micelles against HepG2 tumor cells. Cellular uptake studies confirmed the greater internalization of FA‐PEG‐SS‐CUR by HepG2 cells compared to the non‐targeted PEG‐SS‐CUR. The findings highlight the potential of FA‐PEG‐SS‐CUR as an ideal drug delivery system for CUR due to its facile synthesis and strong self‐assembly performance.

Metabolite identification of emerging disinfection byproduct dibromo-benzoquinone in vivo and in vitro: Multi-strategy mass-spectrometry annotation and toxicity characterization

Halobenzoquinones (HBQs) are emerging disinfection byproducts (DBPs) of high toxicity and also are shared active toxic intermediates of multiple halogenated organic pollutants. Due to the strong oxidizing property and electrophilicity, HBQs exhibit extremely diverse metabolism pathways in organisms. The identification of toxic-decisive metabolites is pivotal, albeit challenging, for understanding the toxicity mechanisms of HBQs. We employed dibromo-benzoquinone (DBBQ) as a representative HBQ, and established a systematic analytical strategy using high-resolution mass spectrometry, which collectively coupled suspect screening (SS), mass defect filtering (MDF), product ion filtering (PIF), isotopic signature filtering (ISF), and molecular networking (MN). As a result, 20 biotransformation products of DBBQ were identified in vivo and in vitro, involving metabolism reactions such as hydroxylation, methylation, methoxylation, acetylation, sulfonation, glucuronidation, glutathionylation, dimerization, and conjugation with amino acids or fatty acids. Quantitative structure-activity relationship (QSAR) analysis and cytotoxicity experiments consistently demonstrated the significantly high toxicity of the fatty acid conjugate compared to the parent compound DBBQ and other metabolites, pinpointing the important role of the fatty acid conjugation in determining the metabolism and toxicity of HBQs. The research conducted a comprehensive evaluation of the metabolism of a typical HBQ with the combination of multiple analytical and toxicity characterization methods, therefore screen out the most important metabolism pathway of HBQs.

Comparison and Assessment of Anti-Inflammatory and Antioxidant Capacity Between EGCG and Phosphatidylcholine-Encapsulated EGCG.

To compare and evaluate the differences between EGCG and phosphatidylcholine-encapsulated EGCG in terms of their anti-inflammatory and antioxidant capacities. In this study, transdermal absorption experiments were conducted to compare the absorption capacity of EGCG and phosphatidylcholine-encapsulated EGCG. Subsequently, the disparity in anti-inflammatory and antioxidant efficacy between EGCG and phosphatidylcholine-encapsulated EGCG were evaluated through cytotoxicity experiments, as well as the determination of cellular inflammatory factors and the measurement of ROS content under different treatment conditions. The concentration of EGCG, encapsulated in phosphatidylcholine, in porcine skin is 40.76 ± 1.29 μg/cm2, which is significantly higher than the concentration of EGCG alone (31.62 ± 2.01 μg/cm2). Also, the ability of phosphatidylcholine-encapsulated EGCG to suppress inflammatory factors such as tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2) was notably superior to that of EGCG alone. Both phosphatidylcholine-encapsulated EGCG and EGCG showed excellent ROS scavenging ability in terms of antioxidant capacity. The percutaneous absorption and anti-inflammatory impact of EGCG encapsulated within phosphatidylcholine were substantially enhanced when compared to EGCG by itself. Additionally, both formulations exhibited enhanced ROS scavenging capacities, albeit the variance between them was not pronounced. These insights furnish a vital theoretical underpinning for the utilization of phosphatidylcholine-encapsulated EGCG in cosmetic applications, specifically for fostering products with anti-inflammatory and antioxidant benefits.

Smart Cancer-Targeting and Super-Sensitive Sensing of Eu3+/Tb3+-Induced Hyaluronan Characteristic Nano-Micelles with Effective Drug Loading and Release.

To avoid the critical problems of effective drugs not being carried to their targeted cancers and their quantity and location not being sensed in situ, this work presents a completely new innovative strategy to achieve both smart cancer targeting (SCT) and super-sensitive sensing (SSS), where one drug carrier works for effective drug loading and release. Herein, malignant melanoma treatment is used as an example of reliable detection and effective therapy. We report two characteristic dumbbell-like nano-micelles and spherical-like nano-micelles of hyaluronan induced by the Eu3+/Tb3+ complexes for effective drug loading and release, respectively. These special Eu3+/Tb3+-loaded nano-micelles (marked as ENM and TNM) have strong and sharp red/green luminescence that can sensitively detect the malignant melanoma drug dacarbazine through changes in fluorescence intensity. Cytotoxicity experiments confirmed that both ENM and TNM are not toxic to normal cells at very high concentrations of 4 mM. However, when loaded with cancer drugs (D-ENM and D-ENM), they both killed cancer cells with more than 40% efficacy at this concentration. The in vivo experiments confirmed that D-ENM and D-TNM can effectively target cancer cells in tissue and effectively impede cancer growth. The detection limits of ENM and TNM in sensing cancer drugs can reach 0.456 μg/mL and 0.139 μg/mL, respectively. Therefore, the reported Eu3+/Tb3+-induced hyaluronan nano-micelles (ENM and TNM) are distinguished carriers of this cancer drug and excellent in situ sensors, and they have highly therapeutic effects with extremely low toxicity to normal cells.

Stereolithography Printing and Mechanical Properties of Polyethylene Glycol Diacrylate/Hexagonal Boron Nitride Ceramic Composites

To enhance the mechanical properties of bioceramic composite bone scaffolds, a composite paste of polyethylene glycol diacrylate (PEGDA) and hexagonal boron nitride (h‐BN) with a solid content of up to 42 wt% was developed in this study. The part was produced using stereolithography (SLA). The SLA printing parameters and material ratios of the paste were optimized through a homogeneous design and mechanical property tests. The results indicate that the single‐line curing width of the PEGDA/h‐BN paste in the XY plane ranged from 172 to 209 μm, while the curing depth of a single layer along the Z‐axis ranged from 99 to 154 μm. Laser power was identified as the primary factor influencing both the width and depth of curing. The compressive strength of the printed sample of PEGDA/h‐BN ceramic composite paste was measured at 222.4 ± 5.6 MPa, which is 61 times greater than the compressive strength of a pure PEGDA structure and comparable to that of cortical bone (100‐230 MPa). Finally, the superior biocompatibility of PEGDA/h‐BN ceramics was confirmed through cytotoxicity experiments. Consequently, PEGDA/h‐BN ceramic composites meet the mechanical properties and biocompatibility requirements necessary for bone tissue applications, indicating promising potential in the field of bone tissue engineering.

Dodecanoyl-L-tryptophan: A Novel Natural Antibiotic Isolated from Mesophotic Sponge-associated Salinicola sp. LHM and its Biological Function

Background: Sponge-associated microbiota plays a crucial role in maintaining host health by providing chemical defense through the synthesis of diverse secondary metabolites. However, research on these secondary metabolites is still in its early stages. Objective: The present study aimed to investigate new natural antibiotics from mesophotic sponge symbiotic microbiota and explore its in vitro antibacterial activity and preliminary biological function. Methods: Bacteria strain Salinicola sp. LHM was isolated from sponge L. birotulata L26 and identified based on the 16S rRNA gene analysis. Subsequently, the strain was fermented using a liquid M9 medium and screened for antibiotics with an antibacterial guiding assay. Extensive chromatographic methods were introduced to isolate the target compound, and its chemical structure was elucidated by spectroscopic analysis (LC-MS, NMR). The minimum inhibitory concentration (MIC) and cytotoxicity experiments evaluated the isolated compound's biological activity. Furthermore, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and quartz crystal microbalance with dissipation (QCM-D) were used to study the bactericidal mechanism of DLT. Finally, the preliminary biological function was explored by performing the cell-feeding experiment. Results: We successfully identified one novel natural antibiotic, dodecanoyl-L-tryptophan (DLT), in Salinicola sp. LHM isolated from mesophotic sponge Lotrochota birotulata L26. DLT exhibited potent antibacterial activity against the Bacillus subtilis and Staphylococcus aureus, with MIC values of 32 μM and 16 μM, respectively. The bactericidal tests showed that DLT broke the cell membrane to cause cell death by leaking the cell's inner content. Furthermore, the cell-feeding experiment proved that DLT producer- Salinicola sp. LHM could feed on the inner content of death cells. In addition, DLT also exhibited cytotoxicity against bronchial epithelial cells BEAS-2B, with an EC50 value of 150 μM, indicating a favorable selectivity profile. result: We successfully identified one novel natural antibiotic, dodecanoyl-L-tryptophan (DLT), in Salinicola sp. LHM isolated from mesophotic sponge Lotrochota birotulata L26. DLT exhibited potent antibacterial activity against the Bacillus subtilis and Staphylococcus aureus, with MIC values of 32 μM and 16 μM, respectively. The bactericidal tests showed that DLT broke the cell membrane to cause cell death by leaking the cell's inner content. Furthermore, the cell-feeding experiment proved that DLT producer- Salinicola sp. LHM could feed on the inner content of death cells. In addition, DLT also exhibited cytotoxicity against bronchial epithelial cells BEAS-2B, with an EC50 value of 150 μM, indicating a favorable selectivity profile. Conclusion: This research identified one novel natural antibiotic DLT and provided initial insights into the chemical defense exerted by Salinicola sp. LHM with its secondary metabolite DLT.

Water-based synthesis of dextran-methacrylate and its use to design hydrogels for biomedical applications

Polysaccharide-based hydrogels are desirable for biomedical applications owing to their biocompatibility and physicochemical tunability. The chemical modification of polysaccharides with photo-sensitive groups, such as methacrylates is a common method to obtain new hydrogel materials. This study introduces a non-toxic water-based method to effectively functionalize dextran with methacrylate groups. The methacrylation reaction with methacrylic anhydride in water in the presence of NaOH was rapid and efficient (85 %−92 % yield), permitting degrees of substitution (DS) up to 62 % within 60 min. An unconventional solid-state photo-crosslinking method was employed to form chemically crosslinked dextran-based hydrogels with LAP (lithium phenyl-2,4,6-trimethylbenzoylphosphinate) as the photoinitiator. By varying the polymer formulations (DS, polymer mass, LAP concentration), a wide range of hydrogels were obtained with various swelling ratios (40–250 %) and release kinetics of model drug and protein biomolecules. Compression modulus values ranged from 32 ± 1 to 342 ± 10 MPa (dry state) and 87 to 8500 kPa (swollen state). Cytotoxicity experiments indicated good biocompatibility for the crosslinked dextran hydrogels. The green synthesis protocols and obtained dextran-based hydrogels with high mechanical strength open up perspectives for applications from tissue engineering to the design of medical devices such as microneedles.

Research on the Corrosion Resistance and Cytotoxicity of Medical Forged Co-28Cr-6Mo Alloy

Co-Cr-Mo alloy as a human body implant material has a long history, because of its excellent corrosion resistance and biocompatibility, and is widely used in human hip joint materials. Co-Cr-Mo alloy in the human body is often in a passivation state; the formation of dense oxide film on the alloy surface prevents further corrosion of the alloy. The main component of the passivation film is the oxide of Cr, so a layer of oxide film formed by Cr on the surface of Co-Cr-Mo alloy is the reason for its good corrosion resistance. In biocompatibility, cytotoxicity is the first choice and necessary option for biological evaluation, and cytotoxicity can quickly detect the effect of materials on cells in a relatively short time. Therefore, this research conducted a comparative evaluation on the corrosion resistance and biocompatibility of forged Co-Cr-Mo alloys produced in domestic and foreign alloys in line with medical standards. Three simulated human body fluids and Princeton electrochemical station were selected for corrosion resistance experiments, and it was found that the corrosion resistance of four alloys in sodium citrate solution inside and outside China would be reduced. All the alloys exhibit secondary passivation behavior in Hanks solution, which improves the corrosion resistance of the alloys. According to the self-corrosion potential Ecorr analysis, the corrosion resistance of domestic B alloy is the best, while that of foreign R31537 alloy is poor. In the biocompatibility experiment, the biocompatibility of Co-Cr-Mo alloy was evaluated through the measurement of contact Angle and cytotoxicity reaction. The experimental results show that Co-Cr-Mo alloy is a hydrophilic material, and the contact Angle of foreign R31537 alloy is smaller, indicating that the surface of R31537 alloy is more suitable for cell adhesion and spreading. According to the qualitative and quantitative analysis of the cytotoxicity experiment, the toxic reaction grade of domestic A, B and R31537 alloy is grade 1, the toxic reaction grade of C alloy is grade 2, and C alloy has a slight toxic reaction.

Metformin-mediated protection against doxorubicin-induced cardiotoxicity

BackgroundA phase II clinical trial of metformin (MET) for the treatment of doxorubicin (DOX)-induced cardiotoxicity (NCT02472353) failed. ObjectivesThe aims of this study were to confirm MET-mediated protection against DOX-induced cardiotoxicity and its mechanism using H9C2 cells, and to establish a Wistar rat model of DOX-induced cardiotoxicity. Subsequently, Wistar rats were utilized to identify clinically relevant indicators for evaluating MET-mediated protection against DOX-induced cardiotoxicity, thereby facilitating early transition towards successful clinical trials. MethodsMET-mediated protection was assessed using cell viability and cytotoxicity experiments. Additionally, intramitochondrial reactive oxygen species (ROS) levels were measured using an ROS fluorescent probe (dihydroethidium) to confirm the oxidative stress mechanism. Eighteen Wistar rats were randomly allocated to the control, DOX, and DOX+MET groups; and the body weight, adverse drug reactions (ADRs), myocardial injury, cardiac function, oxidative stress, and histopathology of heart tissues were compared between groups. ResultsH9C2 cells treated with MET/Dexrazoxane demonstrated dose-dependent protection against DOX-induced cardiotoxicity. The fluorescence intensity of H9C2 cells suggested DOX-induced cardiomyocyte toxicity and MET-mediated protection against DOX-induced cardiotoxicity. In vivo experiments confirmed that a rat model of DOX-induced cardiotoxicity was successfully established, but MET-mediated protection against DOX-induced cardiotoxicity was not demonstrated. This was attributed to insufficient energy intake because of ADRs, such as vomiting. ConclusionsWe confirmed the MET-mediated protection against DOX-induced cardiomyocyte toxicity and its mechanism involving the inhibition of oxidative stress in vitro experiments. It is imperative to investigate the optimal conditions for MET-mediated protection against DOX-induced cardiotoxicity in vivo or clinical trials.

Anticancer Efficacy of Biosynthesized Zinc Oxide and Gold Nanoparticles

Abstract Introduction/Objective Introduction: Advancements in nanoscale materials have led to the exploration of metal oxides for cancer diagnosis and therapy. Zinc oxide nanoparticles (ZnO NPs) and gold nanoparticles (Au NPs) are particularly promising due to their biocompatibility and anticancer properties demonstrated across various cancer cell lines. Objectives This study aimed to isolate fungal endophytes from Eucalyptus sideroxylon leaves and utilize them for the biosynthesis of nanoparticles (ZnO NPs and Au NPs) to assess their anticancer activity. Methods/Case Report Methods: Healthy Eucalyptus sideroxylon samples were collected from a desert research center, and endophytes were isolated and cultivated. The fungal biomass was processed to synthesize ZnO NPs and Au NPs. Cell lines were propagated for cytotoxicity experiments using the MTT assay in a 96-well plate format. Results (if a Case Study enter NA) Results: Biosynthesized ZnO and Au NPs exhibited anticancer activity against HCT-116 and CACO2 cell lines. The IC50 values for ZnO NPs were 5.06 μg/mL for HCT-116 and 6.07 μg/mL for CACO2, while Au NPs showed IC50 values of 5.9 μg/mL for HCT-116 and 1.1 μg/mL for CACO2. ZnO NPs demonstrated dose-dependent toxicity on HCT-116 cells, with increasing concentrations leading to a reduction in cell viability. Similarly, Au NPs exhibited dose-dependent cytotoxicity on both cell lines. Conclusion Conclusion: This study underscores the potential of endophytic fungi for biosynthesizing metal nanoparticles with significant anticancer effects. ZnO NPs displayed superior efficacy against colon cancer cells compared to Au NPs, indicating their potential as therapeutic agents. The findings highlight the importance of exploring natural sources for nanoparticle synthesis and their application in cancer therapy.