Comparative study of susceptibility to methylmercury cytotoxicity in cell types composing rat peripheral nerves: a higher susceptibility of dorsal root ganglion neurons.

Methylmercury is an environmental polluting organometallic compound that exhibits neurotoxicity, as observed in Minamata disease patients. Methylmercury damages peripheral nerves in Minamata patients, causing more damage to sensory nerves than motor nerves. Peripheral nerves are composed of three cell types: dorsal root ganglion (DRG) cells, anterior horn cells (AHCs), and Schwann cells. In this study, we compared cultured these three cell types derived from the rat for susceptibility to methylmercury cytotoxicity, intracellular accumulation of mercury, expression of L-type amino acid transporter 1 (LAT1), which transports methylmercury into cells, and expression of multidrug resistance-associated protein 2 (MRP2), which transports methylmercury-glutathione conjugates into the extracellular space. Of the cells examined, we found that DRG cells were the most susceptible to methylmercury with markedly higher intracellular accumulation of mercury. The constitutive level of LAT1 was higher and that of MRP2 lower in DRG cells compared with those in AHC and Schwann cells. Additionally, decreased cell viability caused by methylmercury was significantly reduced by either the LAT1 inhibitor, JPH203, or siRNA-mediated knockdown of LAT1. On the other hand, an MRP2 inhibitor, MK571, significantly intensified the decrease in the cell viability caused by methylmercury. Our results provide a cellular basis for sensory neve predominant injury in the peripheral nerves of Minamata disease patients.

Targeted photodynamic therapy technique of Janus nanoparticles on breast cancer.

Spherical gold/polyacrylic acid (Au/PAA) polymer-inorganic Janus nanoparticles (JNPs) with simultaneous therapeutic and targeting functions were fabricated. The obtained Au/PAA JNPs were further selectively functionalized with folic acid (FA) and thiol PEG amine (SH-PEG-NH2) on Au sides to provide superior biocompatibility and active targeting, while the other PAA sides were loaded with 5-aminolevulinic acid (5-ALA) to serve as a photosensitizer (PS) for photodynamic therapeutic (PDT) effects on MCF-7 cancer cells. The PS loading of 5-ALA was found to be 83% with an average hydrodynamic size and z-potential of 146 ± 0.8 nm and -6.40 mV respectively for FA-Au/PAA-ALA JNPs. The in vitro PDT study of the JNPs on MCF-7 breast cancer cells under 636 nm laser irradiation indicated the cell viability of 24.7% ± 0.5 for FA-Au/PAA-ALA JNPs at the IC50 value of 0.125 mM. In this regard, the actively targeted FA-Au/PAA-ALA JNPs treatment holds great potential for tumour therapy with high cancer cell-killing efficacy.

The Effect of Glycyrrhizin on the Viability and Proliferation of Dental Pulp Stem Cells Compared to Intracanal Medicaments.

AIM: To study the effect of glycyrrhizin (GA) on the viability and proliferation of dental pulp stem cells (DPSCs) compared with intracanal medicaments. MATERIALS AND METHODS: Third molars of an adult donor were used to obtain the DPSCs. Flow cytometry was utilized to conduct phenotypic analysis for DPSCs. The methyl-thiazol tetrazolium (MTT) test was used to detect the cell viability. Cell proliferation assay was conducted at distinct time intervals: 3, 5, and 7 days. RESULTS: The flow cytometry analysis verified the positive expression of mesenchymal cell surface antigen molecules (CD73, CD90, and CD105) and the absence of hematological markers (CD14, CD34, and CD45) in the DPSCs. The cells that treated with concentrations more than 0.5 mg/mL of Ca(OH2) and triple antibiotic paste (TAP) gave significant decrease in viability in comparison to the untreated cells (p < 0.05). Also, the cells treated with concentrations 50 and 25 µM of GA showed no significant difference compared with the untreated cells (p > 0.05), while concentrations 12.5 and 6.25 µM expressed a significant increase in viability compared with the untreated cells (p < 0.05). At 7 days, cells treated with the three different concentrations of GA (12.5, 25, and 50 µM) demonstrated a significant increase in cell density compared with Ca(OH)2 and TAP-treated cells (p < 0.05). CONCLUSION: Based upon the potential of GA on DPSCs proliferation compared with Ca(OH)2 and TAP, It is conceivable to acknowledge that GA could be used as an intracanal medicaments for revascularization process of necrotic immature teeth. CLINICAL SIGNIFICANCE: This study emphasizes the significance of assessing alternative root canal medicaments and their impact on the proliferation and viability of DPSCs. The results regarding GA, specifically its impact on the viability and growth of DPSCs, provide essential understanding for its potential application as an intracanal medicine. This study adds to the continuous endeavors in identifying safer and more efficient intracanal therapies, which are essential for improving patient outcomes in endodontic operations. How to cite this article: Alrashidi MA, Badawi MF, Elbeltagy MG, et al. The Effect of Glycyrrhizin on the Viability and Proliferation of Dental Pulp Stem Cells Compared to Intracanal Medicaments. J Contemp Dent Pract 2024;25(3):267-275.

Enhancing Curcumin's therapeutic potential in cancer treatment through ultrasound mediated liposomal delivery.

Improving the efficacy of chemotherapy remains a key challenge in cancer treatment, considering the low bioavailability, high cytotoxicity, and undesirable side effects of some clinical drugs. Targeted delivery and sustained release of therapeutic drugs to cancer cells can reduce the whole-body cytotoxicity of the agent and deliver a safe localized treatment to the patient. There is growing interest in herbal drugs, such as curcumin, which is highly noted as a promising anti-tumor drug, considering its wide range of bioactivities and therapeutic properties against various tumors. Conversely, the clinical efficacy of curcumin is limited because of poor oral bioavailability, low water solubility, instability in gastrointestinal fluids, and unsuitable pH stability. Drug-delivery colloid vehicles like liposomes and nanoparticles combined with microbubbles and ultrasound-mediated sustained release are currently being explored as effective delivery modes in such cases. This study aimed to synthesize and study the properties of curcumin liposomes (CLs) and optimize the high-frequency ultrasound release and uptake by a human breast cancer cell line (HCC 1954) through in vitro studies of culture viability and cytotoxicity. CLs were effectively prepared with particles sized at 81 ± 2 nm, demonstrating stability and controlled release of curcumin under ultrasound exposure. In vitro studies using HCC1954 cells, the combination of CLs, ultrasound, and Definity microbubbles significantly improved curcumin's anti-tumor effects, particularly under specific conditions: 15 s of continuous ultrasound at 0.12 W/cm2 power density with 0.6 × 107 microbubbles/mL. Furthermore, the study delved into curcumin liposomes' cytotoxic effects using an Annexin V/PI-based apoptosis assay. The treatment with CLs, particularly in conjunction with ultrasound and microbubbles, amplified cell apoptosis, mainly in the late apoptosis stage, which was attributed to heightened cellular uptake within cancer cells.

3D printed kombucha biomaterial as a tissue scaffold and L929 cell cytotoxicity assay.

Tissue engineering includes the construction of tissue-organ scaffold. The advantage of three-dimensional scaffolds over two-dimensional scaffolds is that they provide homeostasis for a longer time. The microbial community in Symbiotic culture of bacteria and yeast (SCOBY) can be a source for kombucha (kombu tea) production. In this study, it was aimed to investigate the usage of SCOBY, which produces bacterial cellulose, as a biomaterial and 3D scaffold material. 3D printable biomaterial was obtained by partial hydrolysis of oolong tea and black tea kombucha biofilms. In order to investigate the usage of 3D kombucha biomaterial as a tissue scaffold, "L929 cell line 3D cell culture" was created and cell viability was tested in the biomaterial. At the end of the 21st day, black tea showed 51% and oolong tea 73% viability. The cytotoxicity of the materials prepared by lyophilizing oolong and black tea kombucha beverages in fibroblast cell culture was determined. Black tea IC50 value: 7.53 mg, oolong tea IC50 value is found as 6.05 mg. Fibroblast viability in 3D biomaterial + lyophilized oolong and black tea kombucha beverages, which were created using the amounts determined to these values, were investigated by cell culture Fibroblasts in lyophilized and 3D biomaterial showed viability of 58% in black tea and 78% in oolong tea at the end of the 7th day. In SEM analysis, it was concluded that fibroblast cells created adhesion to the biomaterial. 3D biomaterial from kombucha mushroom culture can be used as tissue scaffold and biomaterial.

Inhibition of Prostate Cancer Cell Survival and Proliferation by Carnosic Acid Is Associated with Inhibition of Akt and Activation of AMPK Signaling.

Prostate cancer, accounting for 375,304 deaths in 2020, is the second most prevalent cancer in men worldwide. While many treatments exist for prostate cancer, novel therapeutic agents with higher efficacy are needed to target aggressive and hormone-resistant forms of prostate cancer, while sparing healthy cells. Plant-derived chemotherapy drugs such as docetaxel and paclitaxel have been established to treat cancers including prostate cancer. Carnosic acid (CA), a phenolic diterpene found in the herb rosemary (Rosmarinus officinalis) has been shown to have anticancer properties but its effects in prostate cancer and its mechanisms of action have not been examined. CA dose-dependently inhibited PC-3 and LNCaP prostate cancer cell survival and proliferation (IC50: 64, 21 µM, respectively). Furthermore, CA decreased phosphorylation/activation of Akt, mTOR, and p70 S6K. A notable increase in phosphorylation/activation of AMP-activated kinase (AMPK), acetyl-CoA carboxylase (ACC) and its upstream regulator sestrin-2 was seen with CA treatment. Our data indicate that CA inhibits AKT-mTORC1-p70S6K and activates Sestrin-2-AMPK signaling leading to a decrease in survival and proliferation. The use of inhibitors and small RNA interference (siRNA) approaches should be employed, in future studies, to elucidate the mechanisms involved in carnosic acid's inhibitory effects of prostate cancer.

Baicalin enhances the chemotherapy sensitivity of oxaliplatin-resistant gastric cancer cells by activating p53-mediated ferroptosis.

Gastric cancer is one of the most common malignant tumors, and chemotherapy is the main treatment for advanced gastric cancer. However, chemotherapy resistance leads to treatment failure and poor prognosis in patients with gastric cancer. Multidrug resistance (MDR) is a major challenge that needs to be overcome in chemotherapy. According to recent research, ferroptosis activation is crucial for tumor therapeutic strategies. In this work, we explored the solution to chemoresistance in gastric cancer by investigating the effects of the Chinese medicine monomer baicalin on ferroptosis. Baicalin with different concentrations was used to treat the parent HGC27 and drug-resistant HGC27/L cells of gastric cancer. Cell viability was measured by CCK8, and synergistic effects of baicalin combined with oxaliplatin were evaluated using Synergy Finder software. The effects of baicalin on organelles and cell morphology were investigated using projective electron microscopy. Iron concentration, MDA production and GSH inhibition rate were measured by colorimetry. ROS accumulation was detected by flow cytometry. The ferroptosis-related genes (IREB2, TfR, GPX4, FTH1), P53, and SLC7A11 were analysed by Western blot, and the expression differences of the above proteins between pretreatment and pretreatment of different concentrations of baicalin, were assayed in both parental HGC27 cells and Oxaliplatin-resistant HGC27/L cells. Mechanically, Baicalin disrupted iron homeostasis and inhibits antioxidant defense, resulting in iron accumulation, lipid peroxide aggregation, and specifically targeted and activated ferroptosis by upregulating the expression of tumor suppressor gene p53, thereby activating the SLC7A11/GPX4/ROS pathway mediated by it. Baicalin activates ferroptosis through multiple pathways and targets, thereby inhibiting the viability of oxaliplatin-resistant gastric cancer HGC27/L cells and enhancing the sensitivity to oxaliplatin chemotherapy.

A comprehensive review of advances in hepatocyte microencapsulation: selecting materials and preserving cell viability.

Liver failure represents a critical medical condition with a traditionally grim prognosis, where treatment options have been notably limited. Historically, liver transplantation has stood as the sole definitive cure, yet the stark disparity between the limited availability of liver donations and the high demand for such organs has significantly hampered its feasibility. This discrepancy has necessitated the exploration of hepatocyte transplantation as a temporary, supportive intervention. In light of this, our review delves into the burgeoning field of hepatocyte transplantation, with a focus on the latest advancements in maintaining hepatocyte function, co-microencapsulation techniques, xenogeneic hepatocyte transplantation, and the selection of materials for microencapsulation. Our examination of hepatocyte microencapsulation research highlights that, to date, most studies have been conducted in vitro or using liver failure mouse models, with a notable paucity of experiments on larger mammals. The functionality of microencapsulated hepatocytes is primarily inferred through indirect measures such as urea and albumin production and the rate of ammonia clearance. Furthermore, research on the mechanisms underlying hepatocyte co-microencapsulation remains limited, and the practicality of xenogeneic hepatocyte transplantation requires further validation. The potential of hepatocyte microencapsulation extends beyond the current scope of application, suggesting a promising horizon for liver failure treatment modalities. Innovations in encapsulation materials and techniques aim to enhance cell viability and function, indicating a need for comprehensive studies that bridge the gap between small-scale laboratory success and clinical applicability. Moreover, the integration of bioengineering and regenerative medicine offers novel pathways to refine hepatocyte transplantation, potentially overcoming the challenges of immune rejection and ensuring the long-term functionality of transplanted cells. In conclusion, while hepatocyte microencapsulation and transplantation herald a new era in liver failure therapy, significant strides must be made to translate these experimental approaches into viable clinical solutions. Future research should aim to expand the experimental models to include larger mammals, thereby providing a clearer understanding of the clinical potential of these therapies. Additionally, a deeper exploration into the mechanisms of cell survival and function within microcapsules, alongside the development of innovative encapsulation materials, will be critical in advancing the field and offering new hope to patients with liver failure.

Evaluation of the cytotoxic activities of the essential oil from Pistacia atlantica Desf. oleoresin on human gastric cancer cell lines.

Numerous herbal products have been the subject of research regarding their potential role in cancer prevention or adjuvant therapy. Pistacia atlantica and its main phytochemicals have garnered significant attention for their potential anti-cancer effects. The study aimed to assess the growth inhibitory effects of P. atlantica essential oil (PAEO) on MKN-45 and AGS cells. This study quantified the volatile compounds in PAEO using Gas Chromatography-Mass Spectrometry (GC-MS). Subsequently, MKN-45 and AGS cells were treated with varying concentrations of PAEO (5%, 2.5%, 1.25%, 0.625%, 0.3125%, 0.156%, 0.0781%, 0.0391%, 0.0195%) for 24 h. Cell viability was evaluated through the MTT assay. The impact of PAEO on gene expression was investigated by quantifying the mRNA levels of Bax and Bcl2 in the various experimental groups using quantitative Real-Time PCR (qRT-PCR) analysis. Additionally, flow cytometry was utilized to evaluate apoptosis in the treated cells. The analysis of PAEO revealed that α-pinene was the predominant monoterpene, constituting 87.9% of the oil composition. The cytotoxic effects of PAEO were evaluated, and it was found that the oil significantly reduced the viability of MKN-45 and AGS cells. The IC50 for MKN-45 cells was determined to be 1.94 × 10-3% after 24 h of treatment, while for AGS cells the IC50 was 2.8 × 10-3% after 24 h. Additionally, the research revealed that PAEO triggered a notable rise in apoptotic cells in both AGS and MKN-45 cell lines. Moreover, at the molecular level, the findings indicated an increase in Bax expression and a decrease in Bcl2 mRNA expression, providing further evidence of the induction of apoptosis in both MKN-45 and AGS cell lines following PAEO treatment. The findings of this study offer evidence supporting the cytotoxic effects of PAEO on gastric cancer cell lines by promoting apoptosis. The findings suggest that PAEO may offer potential as a therapeutic candidate in managing and treating gastric cancer.

Improved therapeutic effects on vascular intimal hyperplasia by mesenchymal stem cells expressing MIR155HG that function as a ceRNA for microRNA-205.

Coronary artery bypass grafting (CABG) is an effective treatment for coronary heart disease, with vascular transplantation as the key procedure. Intimal hyperplasia (IH) gradually leads to vascular stenosis, seriously affecting the curative effect of CABG. Mesenchymal stem cells (MSCs) were used to alleviate IH, but the effect was not satisfactory. This work aimed to investigate whether lncRNA MIR155HG could improve the efficacy of MSCs in the treatment of IH and to elucidate the role of the competing endogenous RNA (ceRNA). The effect of MIR155HG on MSCs function was investigated, while the proteins involved were assessed. IH was detected by HE and Van Gieson staining. miRNAs as the target of lncRNA were selected by bioinformatics analysis. qRT-PCR and dual-luciferase reporter assay were performed to verify the binding sites of lncRNA-miRNA. The apoptosis, Elisa and tube formation assay revealed the effect of ceRNA on the endothelial protection of MIR155HG-MSCs. We observed that MIR155HG improved the effect of MSCs on IH by promoting viability and migration. MIR155HG worked as a sponge for miR-205. MIR155HG/miR-205 significantly improved the function of MSCs, avoiding apoptosis and inducing angiogenesis. The improved therapeutic effects of MSCs on IH might be due to the ceRNA role of MIR155HG/miR-205.

New synergistic combination therapy approaches with HDAC inhibitor quisinostat, cisplatin or PARP inhibitor talazoparib for urothelial carcinoma.

Urothelial carcinoma (UC) urgently requires new therapeutic options. Histone deacetylases (HDAC) are frequently dysregulated in UC and constitute interesting targets for the development of alternative therapy options. Thus, we investigated the effect of the second generation HDAC inhibitor (HDACi) quisinostat in five UC cell lines (UCC) and two normal control cell lines in comparison to romidepsin, a well characterized HDACi which was previously shown to induce cell death and cell cycle arrest. In UCC, quisinostat led to cell cycle alterations, cell death induction and DNA damage, but was well tolerated by normal cells. Combinations of quisinostat with cisplatin or the PARP inhibitor talazoparib led to decrease in cell viability and significant synergistic effect in five UCCs and platinum-resistant sublines allowing dose reduction. Further analyses in UM-UC-3 and J82 at low dose ratio revealed that the mechanisms included cell cycle disturbance, apoptosis induction and DNA damage. These combinations appeared to be well tolerated in normal cells. In conclusion, our results suggest new promising combination regimes for treatment of UC, also in the cisplatin-resistant setting.

Induction of heat shock protein expression in SP2/0 transgenic cells and its effect on the production of monoclonal antibodies.

The objective of the current investigation was to evaluate the induction of heat shock proteins (HSPs) in SP2/0 transgenic cells and the effect of these proteins on the production of monoclonal antibodies (mAbs). The SP2/0 cell line expressing the PSG-026 antibody, a biosimilar candidate of golimumab, the culture parameters, and the target protein expression were not justified for industrial production and were used for the experiments. Paracetamol and heat shock were used as chemical and physical inducers of HSPs, respectively. The results showed that paracetamol and heat shock increased the expression of HSP70 and HSP27 at the mRNA and protein levels. The expression of HSPs was greater in paracetamol-treated cells than in heat shock-treated cells. Paracetamol treatment at concentrations above 0.5 mM significantly reduced cell viability and mAb expression. However, treatment with 0.25 mM paracetamol results in delayed cell death and increased mAb production. Heat shock treatment at 45°C for 30 minutes after enhanced mAb expression was applied after pre-treatment with paracetamol. In bioreactor cultures, pretreatment of cells with paracetamol improved cell viability and shortened the lag phase, resulting in increased cell density. The production of mAbs in paracetamol-treated cultures was markedly greater than that in the control. Analysis of protein quality and charge variants revealed no significant differences between paracetamol-treated and control cultures, indicating that the induction of HSPs did not affect protein aggregation or charge variants. These findings suggest that inducing and manipulating HSP expression can be a valuable strategy for improving recombinant protein production in biopharmaceutical processes.

Major endothelial damage markers identified from hemadsorption filters derived from treated patients with septic shock - endoplasmic reticulum stress and bikunin may play a role.

Introduction: In septic patients the damage of the endothelial barrier is decisive leading to circulatory septic shock with disseminated vascular coagulation, edema and multiorgan failure. Hemadsorption therapy leads to rapid resolution of clinical symptoms. We propose that the isolation of proteins adsorbed to hemadsorption devices contributes to the identification of mediators responsible for endothelial barrier dysfunction. Material and methods: Plasma materials enriched to hemadsorption filters (CytoSorb®) after therapy of patients in septic shock were fractionated and functionally characterized for their effect on cell integrity, viability, proliferation and ROS formation by human endothelial cells. Fractions were further studied for their contents of oxidized nucleic acids as well as peptides and proteins by mass spectrometry. Results: Individual fractions exhibited a strong effect on endothelial cell viability, the endothelial layer morphology, and ROS formation. Fractions with high amounts of DNA and oxidized DNA correlated with ROS formation in the target endothelium. In addition, defined proteins such as defensins (HNP-1), SAA1, CXCL7, and the peptide bikunin were linked to the strongest additive effects in endothelial damage. Conclusion: Our results indicate that hemadsorption is efficient to transiently remove strong endothelial damage mediators from the blood of patients with septic shock, which explains a rapid clinical improvement of inflammation and endothelial function. The current work indicates that a combination of stressors leads to the most detrimental effects. Oxidized ssDNA, likely derived from mitochondria, SAA1, the chemokine CXCL7 and the human neutrophil peptide alpha-defensin 1 (HNP-1) were unique for their significant negative effect on endothelial cell viability. However, the strongest damage effect occurred, when, bikunin - cleaved off from alpha-1-microglobulin was present in high relative amounts (>65%) of protein contents in the most active fraction. Thus, a relevant combination of stressors appears to be removed by hemadsorption therapy which results in fulminant and rapid, though only transient, clinical restitution.

Structural investigation of interactions between halogenated flavonoids and the lipid membrane along with their role as cytotoxic agents.

This study focuses on understanding the structural and molecular changes in lipid membranes under the influence of six halogenated flavonoid derivatives differing in the number and position of substitution of chlorine and bromine atoms (D1-D6). Utilizing various analytical techniques, including fluorometric methods, dynamic light scattering (DLS), attenuated Fourier transform infrared spectroscopy (ATR- FTIR), and FT-Raman spectroscopy, the research aims to elucidate the mechanisms underlying the interaction of flavonoids with cell membranes. Additionally, the study includes in silico analyses to explore the physicochemical properties of these compounds and their potential pharmaceutical applications, along with toxicity studies to assess their effects on cancer, normal, and red blood cells. Our study showed the ability of halogenated derivatives to interact mostly with the outer part of the membrane, especially in the lipid heads region however, some of them were able to penetrate deeper into the membrane and affect the fluidity of hydrocarbon chains. The potential to reduce cancer cell viability, the lack of toxicity towards erythrocytes, and the favourable physicochemical and pharmacokinetic properties suggest these halogenated flavonoids potential candidates for exploring their potential for medical use.

Chaga mushroom extract suppresses oral cancer cell growth via inhibition of energy metabolism.

Oral cancer stands as a prevalent maligancy worldwide; however, its therapeutic potential is limited by undesired effects and complications. As a medicinal edible fungus, Chaga mushroom (Inonotus obliquus) exhibits anticancer effects across diverse cancers. Yet, the precise mechanisms underlying its efficacy remain unclear. We explored the detailed mechanisms underlying the anticancer action of Chaga mushroom extract in oral cancer cells (HSC-4). Following treatment with Chaga mushroom extracts, we analyzed cell viability, proliferation capacity, glycolysis, mitochondrial respiration, and apoptosis. Our findings revealed that the extract reduced cell viability and proliferation of HSC-4 cells while arresting their cell cycle via suppression of STAT3 activity. Regarding energy metabolism, Chaga mushroom extract inhibited glycolysis and mitochondrial membrane potential in HSC-4 cells, thereby triggering autophagy-mediated apoptotic cell death through activation of the p38 MAPK and NF-κB signaling pathways. Our results indicate that Chaga mushroom extract impedes oral cancer cell progression, by inhibiting cell cycle and proliferation, suppressing cancer cell energy metabolism, and promoting autophagy-mediated apoptotic cell death. These findings suggest that this extract is a promising supplementary medicine for the treatment of patients with oral cancer.

Protection of Si Nanowires against Aß Toxicity by the Inhibition of Aß Aggregation.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the accumulation of amyloid beta (Aß) plaques in the brain. Aß1-42 is the main component of Aß plaque, which is toxic to neuronal cells. Si nanowires (Si NWs) have the advantages of small particle size, high specific surface area, and good biocompatibility, and have potential application prospects in suppressing Aß aggregation. In this study, we employed the vapor-liquid-solid (VLS) growth mechanism to grow Si NWs using Au nanoparticles as catalysts in a plasma-enhanced chemical vapor deposition (PECVD) system. Subsequently, these Si NWs were transferred to a phosphoric acid buffer solution (PBS). We found that Si NWs significantly reduced cell death in PC12 cells (rat adrenal pheochromocytoma cells) induced by Aß1-42 oligomers via double staining with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and fluorescein diacetate/propyl iodide (FDA/PI). Most importantly, pre-incubated Si NWs largely prevented Aß1-42 oligomer-induced PC12 cell death, suggesting that Si NWs exerts an anti-Aß neuroprotective effect by inhibiting Aß aggregation. The analysis of Fourier Transform Infrared (FTIR) results demonstrates that Si NWs reduce the toxicity of fibrils and oligomers by intervening in the formation of ß-sheet structures, thereby protecting the viability of nerve cells. Our findings suggest that Si NWs may be a potential therapeutic agent for AD by protecting neuronal cells from the toxicity of Aß1-42.

Generation of Eroded Nanoplastics from Domestic Wastes and Their Impact on Macrophage Cell Viability and Gene Expression.

This study reports an innovative approach for producing nanoplastics (NP) from various types of domestic waste plastics without the use of chemicals. The plastic materials used included water bottles, styrofoam plates, milk bottles, centrifuge tubes, to-go food boxes, and plastic bags, comprising polyethylene terephthalate (PET), polystyrene (PS), polypropylene (PP), high-density polyethylene (HDPE), and Poly (Ethylene-co-Methacrylic Acid) (PEMA). The chemical composition of these plastics was confirmed using Raman and FTIR spectroscopy, and they were found to have irregular shapes. The resulting NP particles ranged from 50 to 400 nm in size and demonstrated relative stability when suspended in water. To assess their impact, the study investigated the effects of these NP particulates on cell viability and the expression of genes involved in inflammation and oxidative stress using a macrophage cell line. The findings revealed that all types of NP reduced cell viability in a concentration-dependent manner. Notably, PS, HDPE, and PP induced significant reductions in cell viability at lower concentrations, compared to PEMA and PET. Moreover, exposure to NP led to differential alterations in the expression of inflammatory genes in the macrophage cell line. Overall, this study presents a viable method for producing NP from waste materials that closely resemble real-world NP. Furthermore, the toxicity studies demonstrated distinct cellular responses based on the composition of the NP, shedding light on the potential environmental and health impacts of these particles.

Target Cell Extraction and Spectrum-Effect Relationship Coupled with BP Neural Network Classification for Screening Potential Bioactive Components in Ginseng Extract with a Protective Effect against Myocardial Damage.

Cardiovascular disease has become a common ailment that endangers human health, having garnered widespread attention due to its high prevalence, recurrence rate, and sudden death risk. Ginseng possesses functions such as invigorating vital energy, enhancing vein recovery, promoting body fluid and blood nourishment, calming the nerves, and improving cognitive function. It is widely utilized in the treatment of various heart conditions, including palpitations, chest pain, heart failure, and other ailments. Although numerous research reports have investigated the cardiovascular activity of single ginsenoside, there remains a lack of systematic research on the specific components group that predominantly contribute to cardiovascular efficacy in ginseng medicinal materials. In this research, the spectrum-effect relationship, target cell extraction, and BP neural network classification were used to establish a rapid screening system for potential active substances. The results show that red ginseng extract (RGE) can improve the decrease in cell viability and ATP content and inhibit the increase in ROS production and LDH release in OGD-induced H9c2 cells. A total of 70 ginsenosides were identified in RGE using HPLC-Q-TOF-MS/MS analysis. Chromatographic fingerprints were established for 12 batches of RGE by high-performance liquid chromatography (HPLC). A total of 36 common ingredients were found in 12 batches of RGE. The cell viability, ATP, ROS, and LDH of 12 batches RGE were tested to establish gray relationship analysis (GRA) and partial least squares discrimination analysis (PLS-DA). BP neural network classification and target cell extraction were used to narrow down the scope of Spectral efficiency analysis and screen the potential active components. According to the cell experiments, RGE can improve the cell viability and ATP content and reduce the oxidative damage. Then, seven active ingredients, namely, Ginsenoside Rg1, Rg2, Rg3, Rb1, Rd, Re, and Ro, were screened out, and their cardiovascular activity was confirmed in the OGD model. The seven ginsenosides were the main active substances of red ginseng in treating myocardial injury. This study offers a reference for quality control in red ginseng and preparations containing red ginseng for the management of cardiovascular diseases. It also provides ideas for screening active ingredients of the same type of multi-pharmacologically active traditional Chinese medicines.

Antioxidant and Cytotoxic Properties of Berberis vulgaris (L.) Stem Bark Dry Extract.

Berberis vulgaris (L.) has remarkable ethnopharmacological properties and is widely used in traditional medicine. The present study investigated B. vulgaris stem bark (Berberidis cortex) by extraction with 50% ethanol. The main secondary metabolites were quantified, resulting in a polyphenols content of 17.6780 ± 3.9320 mg Eq tannic acid/100 g extract, phenolic acids amount of 3.3886 ± 0.3481 mg Eq chlorogenic acid/100 g extract and 78.95 µg/g berberine. The dried hydro-ethanolic extract (BVE) was thoroughly analyzed using Ultra-High-Performance Liquid Chromatography coupled with High-Resolution Mass Spectrometry (UHPLC-HRMS/MS) and HPLC, and 40 bioactive phenolic constituents were identified. Then, the antioxidant potential of BVE was evaluated using three methods. Our results could explain the protective effects of Berberidis cortex EC50FRAP = 0.1398 mg/mL, IC50ABTS = 0.0442 mg/mL, IC50DPPH = 0.2610 mg/mL compared to ascorbic acid (IC50 = 0.0165 mg/mL). Next, the acute toxicity and teratogenicity of BVE and berberine-berberine sulfate hydrate (BS)-investigated on Daphnia sp. revealed significant BS toxicity after 24 h, while BVE revealed considerable toxicity after 48 h and induced embryonic developmental delays. Finally, the anticancer effects of BVE and BS were evaluated in different tumor cell lines after 24 and 48 h of treatments. The MTS assay evidenced dose- and time-dependent antiproliferative activity, which was higher for BS than BVE. The strongest diminution of tumor cell viability was recorded in the breast (MDA-MB-231), colon (LoVo) cancer, and OSCC (PE/CA-PJ49) cell lines after 48 h of exposure (IC50 < 100 µg/mL). However, no cytotoxicity was reported in the normal epithelial cells (HUVEC) and hepatocellular carcinoma (HT-29) cell lines. Extensive data analysis supports our results, showing a significant correlation between the BVE concentration, phenolic compounds content, antioxidant activity, exposure time, and the viability rate of various normal cells and cancer cell lines.

Differential Anti-Fibrotic and Remodeling Responses of Human Dermal Fibroblasts to Artemisia sp., Artemisinin, and Its Derivatives.

Fibrosis is a ubiquitous pathology, and prior studies have indicated that various artemisinin (ART) derivatives (including artesunate (AS), artemether (AM), and dihydroartemisinin (DHA)) can reduce fibrosis in vitro and in vivo. The medicinal plant Artemisia annua L. is the natural source of ART and is widely used, especially in underdeveloped countries, to treat a variety of diseases including malaria. A. afra contains no ART but is also antimalarial. Using human dermal fibroblasts (CRL-2097), we compared the effects of A. annua and A. afra tea infusions, ART, AS, AM, DHA, and a liver metabolite of ART, deoxyART (dART), on fibroblast viability and expression of key fibrotic marker genes after 1 and 4 days of treatment. AS, DHA, and Artemisia teas reduced fibroblast viability 4 d post-treatment in up to 80% of their respective controls. After 4 d of treatment, AS DHA and Artemisia teas downregulated ACTA2 up to 10 fold while ART had no significant effect, and AM increased viability by 10%. MMP1 and MMP3 were upregulated by AS, 17.5 and 32.6 fold, respectively, and by DHA, 8 and 51.8 fold, respectively. ART had no effect, but A. annua and A. afra teas increased MMP3 5 and 16-fold, respectively. Although A. afra tea increased COL3A1 5 fold, MMP1 decreased >7 fold with no change in either transcript by A. annua tea. Although A. annua contains ART, it had a significantly greater anti-fibrotic effect than ART alone but was less effective than A. afra. Immunofluorescent staining for smooth-muscle α-actin (α-SMA) correlated well with the transcriptional responses of drug-treated fibroblasts. Together, proliferation, qPCR, and immunofluorescence results show that treatment with ART, AS, DHA, and the two Artemisia teas yield differing responses, including those related to fibrosis, in human dermal fibroblasts, with evidence also of remodeling of fibrotic ECM.