Cell Survival Rate Research Articles

Investigating the Pharmacological Mechanisms of Total Flavonoids from Eucommia ulmoides Oliver Leaves for Ischemic Stroke Protection.

The aim of this study was to explore how the total flavonoids from Eucommia ulmoides leaves (EULs) regulate ischemia-induced nerve damage, as well as the protective effects mediated by oxidative stress. The cell survival rate was significantly improved compared to the ischemic group (p < 0.05) after treatment with the total flavonoids of EULs. The levels of reactive oxygen species (ROS), lactate dehydrogenase (LDH), and malondialdehyde (MDA) decreased, while catalase (CAT) and glutathione (GSH) increased, indicating that the total flavonoids of EULs can significantly alleviate neurological damage caused by ischemic stroke by inhibiting oxidative stress (p < 0.01). The mRNA expression level of VEGF increased (p < 0.01), which was consistent with the protein expression results. Meanwhile, the protein expression of ERK and CCND1 increased (p < 0.01), suggesting that the total flavonoids of EULs could protect PC12 cells from ischemic injury via VEGF-related pathways. MCAO rat models indicated that the total flavonoids of EULs could reduce brain ischemia-reperfusion injury. In conclusion, this study demonstrates the potential mechanisms of the total flavonoids of EULs in treating ischemic stroke and their potential therapeutic effects in reducing ischemic injury, which provides useful information for ischemic stroke drug discovery.

Role of the PARP1/NF-κB Pathway in DNA Damage and Apoptosis of TK6 Cells Induced by Hydroquinone.

Hydroquinone(HQ) is a widely used industrial raw material and is a topical lightening product found in over-the-counter products. However, inappropriate exposure to HQ can pose certain health hazards. This study aims to explore the mechanisms of DNA damage and cell apoptosis caused by HQ, with a focus on whether HQ activates the nuclear factor-κB (NF-κB) pathway to participate in this process and to investigate the correlation between the NF-κB pathway activation and poly(ADP-ribose) polymerase 1(PARP1). Through various experimental techniques, such as DNA damage detection, cell apoptosis assessment, cell survival rate analysis, immunofluorescence, and nuclear-cytoplasmic separation, the cytotoxic effects of HQ were verified, and the activation of the NF-κB pathway was observed. Simultaneously, the relationship between the NF-κB pathway and PARP1 was verified by shRNA interference experiments. The results showed that HQ could significantly activate the NF-κB pathway, leading to a decreased cell survival rate, increased DNA damage, and cell apoptosis. Inhibiting the NF-κB pathway could significantly reduce HQ-induced DNA damage and cell apoptosis and restore cell proliferation and survival rate. shRNA interference experiments further indicated that the activation of the NF-κB pathway was regulated by PARP1. This study confirmed the important role of the NF-κB pathway in HQ-induced DNA damage and cell apoptosis and revealed that the activation of the NF-κB pathway was mediated by PARP1. This research provides important clues for a deeper understanding of the toxic mechanism of HQ.

High-throughput assays to assess variant effects on disease.

Interpreting the wealth of rare genetic variants discovered in population-scale sequencing efforts and deciphering their associations with human health and disease present a critical challenge due to the lack of sufficient clinical case reports. One promising avenue to overcome this problem is deep mutational scanning (DMS), a method of introducing and evaluating large-scale genetic variants in model cell lines. DMS allows unbiased investigation of variants, including those that are not found in clinical reports, thus improving rare disease diagnostics. Currently, the main obstacle limiting the full potential of DMS is the availability of functional assays that are specific to disease mechanisms. Thus, we explore high-throughput functional methodologies suitable to examine broad disease mechanisms. We specifically focus on methods that do not require robotics or automation but instead use well-designed molecular tools to transform biological mechanisms into easily detectable signals, such as cell survival rate, fluorescence or drug resistance. Here, we aim to bridge the gap between disease-relevant assays and their integration into the DMS framework.

Soot formation and its hazards in battery thermal runaway

As an increasingly important solution for the energy industry, batteries are widely used in electric vehicles and energy storage systems. However, thermal runaway of batteries is a serious safety hazard. In this process, the materials in the battery undergo thermal decomposition and combustion, resulting in the formation of soot and other harmful byproducts and posing a significant threat to the environment and human health. In this work, LiFePO4 and ternary lithium batteries are selected as experimental subjects to comprehensively evaluate the soot hazard in the thermal runaway process. The LiFePO4 and ternary lithium battery soot samples exhibited a typical "core-shell" structure, with lattice spacings ranging between 0.36-0.46 and 0.35–0.46 nm, respectively. The surfaces of these materials are covered with functional groups, including C–C, C–O, and O–H bonds. Soot samples taken from the thermal runaway of ternary lithium batteries also contain O–CO and π bonds, consistent with the functional groups in wood soot. Through EDS and XPS characterization, it is evident that the LiFePO4 battery soot contains C, O, Li, F, P, and Fe, while the ternary lithium battery soot, in addition to these elements, also contains Ni, Co, and Mn. The battery soot samples exhibited significant cytotoxicity to human cells, such as lung cells (MRC-5) and neural cells (SH-SY5Y). With high concentrations of soot, the survival rate of lung cells and nerve cells is low. Compared to wood soot, battery soot causes greater damage to human lungs and neural cells. The research in this work contributes to a better understanding of the hazardous characteristics of soot in battery thermal runaway and its potential threats to human health, offering a crucial reference for enhancing battery safety and emergency responses.

Association between GPRC5A expression and carboplatin efficacy in triple-negative breast cancer patients.

e13142 Background: Triple-negative breast cancer (TNBC) patients often face a grim prognosis, primarily due to their resistance to chemotherapy. Carboplatin is a common treatment for TNBC, particularly effective in BRCA1/2 mutations, but its efficacy varies in BRCA1/2 wild-type patients. A previous study identified GPRC5A expression as a biomarker for carboplatin chemotherapy in ovarian cancer, yet its association with carboplatin efficacy in TNBC remains unknown. This study aims to investigate whether GPRC5A can serve as a biomarker for predicting carboplatin efficacy in TNBC and to elucidate the underlying mechanisms. Methods: Analyzing clinical data from the past 5 years in Division of Breast &amp; Thyroid Surgery in Jiangsu Province Hospital, we identified 199 TNBC patients treated with carboplatin. GPRC5A expression in TNBC tumors was assessed via immunohistochemistry (IHC) and evaluated by three individual pathologists. Expression levels were categorized as low (low), low (mild), high (moderate), and high (high). The Chi-square test was employed to assess the correlation between GPRC5A expression and carboplatin efficacy. TNBC-derived organoids were used to validate the relationship between GPRC5A expression and carboplatin sensitivity. Results: Among the 199 TNBC patients, 31 (17.2%) had BRCA1/2 mutations. The pathologic complete response (pCR) rate in BRCA1/2 mutation patients receiving carboplatin was 83.9%, compared to 61.3% in BRCA1/2 wild-type patients (p=0.016). Analyzing the relationship between GPRC5A expression and BRCA1/2 gene mutations in 145 patient samples revealed no significant association (p=0.37). Irrespective of BRCA1/2 mutation status, patients with low/mild GPRC5A expression had a higher pCR rate (74.1%) compared to those with moderate/high GPRC5A expression (45%, p&lt;0.001). TNBC-derived organoids treated with carboplatin showed a cell survival rate of 31.25% (±8.5%) in low GPRC5A expression organoids and 56.25% (±12.6%) in high GPRC5A expression organoids (p=0.017). Conclusions: Our study demonstrates a correlation between GPRC5A expression and BRCA1/2 mutation status in TNBC. Furthermore, TNBC patients with low GPRC5A expression exhibited a more favorable response to carboplatin treatment, suggesting GPRC5A could be a potential biomarker for predicting carboplatin efficacy in TNBC patients.

Establishment and application of a brain cell line derived from Plectropomus leopardus

Plectropomus leopardus is an economically valuable marine farmed fish. However, diseases have seriously restricted the healthy development of its breeding industry. Cell line is an important in vitro research system in the fields of disease control, environmental toxicology, nanotechnology, and so on. However, the application of marine fish cell lines is far from the expected level, and many species have not yet been reported to establish cell lines. In our study, we developed a brain cell line derived from P. leopardus, designated as PLB, and investigated its susceptibility to bacterial agents and heavy metal exposure. The findings indicated that PLB cell lines grew fastest in L-15 medium supplemented with 20 % fetal bovine serum (FBS) at 26 °C. The established cell line was identified by 18 S rRNA gene sequencing as being derived from P. leopardus. Chromosome analysis revealed that the PLB cell line had a chromosome count of 48. The transfection efficiency of PLB cells was about 27 % by liposome transfection method, indicating that PLB cell lines offer utility for conducting functional investigations of exogenous genes. In addition, the bacterial sensitivity analysis results indicated that PLB cells exhibited susceptibility to both Vibrio harveyi and Edwardsiella tarda, furthermore, PLB cells displayed heightened sensitivity towards V. harveyi in comparison to E. tarda. The outcomes from the heavy metal toxicity experiments demonstrated significant toxicity of three heavy metals (Hg2+, Cu2+ and Cd2+) towards PLB cells, with Hg2+ exhibiting the highest degree of toxicity among them. Moreover, there was a dose-dependent relationship between cell survival rate of PLB and heavy metal concentration. In summary, PLB cell lines represent a promising tool for conducting in vitro analyses of foreign gene functionality, bacterial susceptibility, and heavy metal toxicity. It helps ensure the safety of aquatic breeding environments and also supports genetic enhancements in fish fry, promoting the development of traits such as increased growth and disease resistance, which are vital for aquaculture progress.

Research on the Protective Effects of Different Chinese Medicine Compounds on Gefitinib-Induced Hepatotoxicity

Abstract Objective Our objective was to screen drugs with good protective effects on gefitinib-induced hepatotoxicity. Methods Fifty-four specific pathogen-free-grade male mice of the Institute of Cancer Research were randomly divided into a normal group, gefitinib group, glutathione group, ligustrazine group, silymarin group, glycyrrhizic acid group, baicalin group, paeoniflorin group, and matrine group, with six mice in each group. Except for the normal group, the remaining groups of mice were intragastrically administered 400 mg·kg−1 of gefitinib for 16 days to induce liver injury. Mice in each treatment group were intragastrically administered 100 mg·kg−1 of the corresponding drug 30 minutes after gefitinib administration each day. The normal group and model group mice were intragastrically administered with an equal volume of 0.5% carboxymethylcellulose sodium (CMC-Na), and the administration volume was 10 mg·kg−1. Then, 30 minutes after the last administration, blood was collected from the retro-orbital venous plexus, and the mice were killed by cervical dislocation to obtain liver weight and calculate the liver index. Liver pathological changes were observed by hematoxylin–eosin (HE) staining; the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were detected using biochemical kits. AML12 cells were cultured in a medium containing drugs for 30 minutes. Except for the normal group, the remaining groups were induced cell damage with 20 μmoL·L−1 gefitinib for 24 hours. Cell viability was detected using a cell counting kit-8, and the levels of ALT, AST, and lactate dehydrogenase (LDH) in the cell culture supernatant were measured using biochemical kits. Results Animal experiments showed that compared with the gefitinib group, glycyrrhizic acid and baicalin significantly increased the body weight of mice (p &lt; 0.01) and decreased the liver index and levels of ALT and AST (p &lt; 0.05); ligustrazine and silymarin significantly increased the body weight of mice (p &lt; 0.01) and decreased the level of AST (p &lt; 0.05); paeoniflorin and matrine significantly decreased the levels of ALT and AST (p &lt; 0.01). HE staining showed that the liver tissue of mice in the gefitinib group presented a large number of inflammatory cell infiltrations and disordered arrangement of hepatic cords; glutathione, glycyrrhizic acid, baicalin, paeoniflorin, and matrine significantly alleviated pathological damage to mouse liver tissue. Cell experiments showed that all drugs could alleviate gefitinib-induced damage to AML12 cells to varying degrees, among which glycyrrhizic acid, baicalin, and paeoniflorin had better protective effects, with cell survival rates increased to 96.4, 81.1, and 78.2%, respectively. Compared with the gefitinib group, glycyrrhizic acid significantly reduced the levels of ALT, AST, and LDH (p &lt; 0.05); silymarin, baicalin, and paeoniflorin significantly reduced the levels of ALT and LDH (p &lt; 0.05). Conclusion Glycyrrhizic acid, baicalin, and paeoniflorin all have good protective effects against gefitinib-induced hepatotoxicity, among which glycyrrhizic acid has the best effect.

Preliminary study on the effect of pre-freezing methods on lyophilization quality and storage stability of probiotics

This study investigated the impact of pre-freezing techniques on the quality and storage stability of probiotics. Pediococcus acidilactici CCFM6432, Lactiplantibacillus plantarum CN2018, and Bifidobacterium breve CCFM1025 were subjected to freezing at −80 °C and −196 °C using liquid nitrogen, respectively. The results indicated that liquid nitrogen pre-freezing did not cause cell death during the freezing phase. Following lyophilization, liquid nitrogen pre-freezing did not affect the survival rates of P. acidilactici CCFM6432 and L. plantarum CN2018; however, it significantly decreased the survival rate of B. breve CCFM1025 (p < 0.05). Differential Scanning Calorimetry (DSC) analysis revealed that liquid nitrogen pre-freezing increased the melting enthalpy of the cell suspension. A linear correlation between the bacterial cell survival rate and moisture content was observed, with survival rates at the pre-freezing temperature of −196 °C slightly lower than those at −80 °C. Liquid nitrogen granulation pre-freezing enhanced the storage stability of B. breve CCFM1025. This research offers valuable insights into the potential development of pre-freezing techniques for application in the food industry to enhance the quality and storage stability of probiotics.

Sevoflurane postconditioning attenuates cardiomyocytes hypoxia/reoxygenation injury via PI3K/AKT pathway mediated HIF-1α to regulate the mitochondrial dynamic balance

BackgroundMyocardial ischemia-reperfusion injury (I/RI) is a major cause of perioperative cardiac-related adverse events and death. Studies have shown that sevoflurane postconditioning (SpostC), which attenuates I/R injury and exerts cardioprotective effects, regulates mitochondrial dynamic balance via HIF-1α, but the exact mechanism is unknown. This study investigates whether the PI3K/AKT pathway in SpostC regulates mitochondrial dynamic balance by mediating HIF-1α, thereby exerting myocardial protective effects.MethodsThe H9C2 cardiomyocytes were cultured to establish the hypoxia-reoxygenation (H/R) model and randomly divided into 4 groups: Control group, H/R group, sevoflurane postconditioning (H/R + SpostC) group and PI3K/AKT blocker (H/R + SpostC + LY) group. Cell survival rate was determined by CCK-8; Apoptosis rate was determined by flow cytometry; mitochondrial membrane potential was evaluated by Mito Tracker™ Red; mRNA expression levels of AKT, HIF-1α, Opa1and Drp1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR); Western Blot assay was used to detect the protein expression levels of AKT, phosphorylated AKT (p-AKT), HIF-1α, Opa1 and Drp1.ResultsCompared with the H/R group, the survival rate of cardiomyocytes in the H/R + SpostC group increased, the apoptosis rate decreased and the mitochondrial membrane potential increased. qRT-PCR showed that the mRNA expression of HIF-1α and Opa1 were higher in the H/R + SpostC group compared with the H/R group, whereas the transcription level of Drp1 was lower in the H/R + SpostC group. In the H/R + SpostC + LY group, the mRNA expression of HIF-1α was lower than the H/R + SpostC group. There was no difference in the expression of Opa1 mRNA between the H/R group and the H/R + SpostC + LY group. WB assay results showed that compared with the H/R group, the protein expression levels of HIF-1α, Opa1, P-AKT were increased and Drp1 protein expression levels were decreased in the H/R + SpostC group. HIF-1α, P-AKT protein expression levels were decreased in the H/R + SpostC + LY group compared to the H/R + SpostC group.ConclusionSpostC mediates HIF-1α-regulated mitochondrial fission and fusion-related protein expression to maintain mitochondrial dynamic balance by activating the PI3K/AKT pathway and increasing AKT phosphorylation, thereby attenuating myocardial I/R injury.

CD276 enhances sunitinib resistance in clear cell renal cell carcinoma by promoting DNA damage repair and activation of FAK-MAPK signaling pathway.

This study aimed to explore the effect of CD276 expression on the sunitinib sensitivity of clear cell renal cell carcinoma (ccRCC) cell and animal models and the potential mechanisms involved. CD276 expression levels of ccRCC and normal samples were analyzed via online databases and real-time quantitative PCR (RT-qPCR). CD276 was knocked down in ccRCC cell models (sunitinib-resistant 786-O/R cells and sunitinib-sensitive 786-O cells) using shRNA transfection, and the cells were exposed to a sunitinib (2 µM) environment. Cells proliferation was then analyzed using MTT assay and colony formation experiment. Alkaline comet assay, immunofluorescent staining, and western blot experiments were conducted to assess the DNA damage repair ability of the cells. Western blot was also used to observe the activation of FAK-MAPK pathway within the cells. Finally, a nude mouse xenograft model was established and the nude mice were orally administered sunitinib (40mg/kg/d) to evaluate the in vivo effects of CD276 knockdown on the therapeutic efficacy of sunitinib against ccRCC. CD276 was significantly upregulated in both ccRCC clinical tissue samples and cell models. In vitro experiments showed that knocking down CD276 reduced the survival rate, IC50 value, and colony-forming ability of ccRCC cells. Knocking down CD276 increased the comet tail moment (TM) values and γH2AX foci number, and reduced BRCA1 and RAD51 protein levels. Knocking down CD276 also decreased the levels of p-FAK, p-MEK, and p-ERK proteins. Knocking down CD276 effectively improved the sensitivity of ccRCC cell and animal models to sunitinib treatment.

Evaluation of extruded starch foam for glucose-supplying biomaterials

The survival rate of mesenchymal stem cells (MSC), a crucial factor in tissue engineering, is highly dependent on glucose supply. The purpose of this paper is to study the potential of starch foams as glucose suppliers. It is investigated through in vitro hydrolysis by amyloglucosidase in conditions that respect physiological constraints (37 °C and pH 7.4), including a duration of 21 days, and no stirring. Nine extruded starch foams with amylose contents ranging from 0 to 74 %, with various cell wall thicknesses (50 to 300 μm), and different crystallinities (0–30 %) were hydrolysed. These kinetics were fitted by a model which shows that the maximum rate of hydrolysis varies from 7 to 100 %, and which allows the rate of hydrolysis at 21 days to be calculated precisely. The results reveal the major role of amylose in glucose delivery kinetics, and the secondary roles of crystallinity and cell wall thickness of the foams. Additional hydrolysis of starch films revealed that thickness positively influences the amylose chain reorganisation during hydrolysis, which, in slows down and limits glucose delivery. A simple glucose delivery kinetics analysis procedure is proposed to select samples for testing as MSC glucose suppliers.

3D tumor spheroids promote activation, expansion, and anti-tumor effects of tumor-infiltrating lymphocytes in vitro

The adoptive immunotherapy mediated by tumor-infiltrating lymphocytes (TILs) has shown definite efficacy against various solid tumors. However, the inefficiency of the conventional method based on in vitro expansion of TILs fails to achieve the cell count and high tumor-killing activity required for therapeutic purposes. This study investigated the effect of 3D tumor spheroids on the activation and expansion of TILs in vitro, aiming to provide a novel approach for the expansion of TILs. We procured TILs and primary tumor cells from surgical samples of lung cancer patients and then compared the impacts of lung cancer cell line NCI-H1975 and primary lung cancer cells cultured under 2D and 3D conditions on the activation, expansion, and anti-tumor activity of TILs. Furthermore, we added the programmed cell death protein 1 (PD-1) antibody into the co-culture of primary tumor cells and TILs within a 3D environment to assess the effects of the antibody on TILs. The results showed that compared with 2D cultured tumor cells, the 3D cultured H1975 cells significantly enhanced the expansion of TILs, increasing the proportion of CD3+/CD8+ cells in TILs to 61.6%. The 3D primary tumor model also enhanced the proportion of CD3+/CD8+ cells in TILs (45.5%, 54.4%), induced apoptosis of tumor epithelial cells and decreased the overall tumor cells survival rate (16.7%) after co-culture. PD-1 antibodies further improved the in vitro expansion capacity of TILs mediated by 3D tumor spheroids, resulting in the proportions of 50.9% and 57.0% for CD3+/CD8+ cells and enhancing the antitumor activity significantly (reducing the overall tumor survival rate to 9.36%). In summary, the use of 3D tumor spheroids significantly promoted the expansion and improved the anti-tumor effect of TILs, and the use of the PD-1 antibody further promoted the expansion and tumor-killing effect of TILs.

A Chitosan Scaffold Supports the Enhanced and Prolonged Differentiation of HiPSCs into Nucleus Pulposus-like Cells.

Intervertebral disc degeneration (IDD) is a progressive condition and stands as one of the primary causes of low back pain. Cell therapy that uses nucleus pulposus (NP)-like cells derived from human induced pluripotent stem cells (hiPSCs) holds great promise as a treatment for IDD. However, the conventional two-dimensional (2D) monolayer cultures oversimplify cell-cell interactions, leading to suboptimal differentiation efficiency and potential loss of phenotype. While three-dimensional (3D) culture systems like Matrigel improve hiPSC differentiation efficiency, they are limited by animal-derived materials for translation, poorly defined composition, short-term degradation, and high cost. In this study, we introduce a new 3D scaffold fabricated using medical-grade chitosan with a high degree of deacetylation. The scaffold features a highly interconnected porous structure, near-neutral surface charge, and exceptional degradation stability, benefiting iPSC adhesion and proliferation. This scaffold remarkably enhances the differentiation efficiency and allows uninterrupted differentiation for up to 25 days without subculturing. Notably, cells differentiated on the chitosan scaffold exhibited increased cell survival rates and upregulated gene expression associated with extracellular matrix secretion under a chemically defined condition mimicking the challenging microenvironment of intervertebral discs. These characteristics qualify the chitosan scaffold-cell construct for direct implantation, serving as both a structural support and a cellular source for enhanced stem cell therapy for IDD.

Indocyanine green-loaded N-doped carbon quantum dot nanoparticles for effective photodynamic therapy and cell imaging of melanoma cancer: in vitro, ex vivo and in vivo study

Background Indocyanine Green (ICG) as an agent for photodynamic therapy (PDT) of melanoma cancer has low quantum yield, short circulation half-life, poor photo-stability, and tendency to aggregation. Purpose N-doped carbon quantum dot (CQD) nanoparticle was applied to encapsulate ICG and overcome ICG obstacle in PDT with simultaneous cell imaging property. Methods CQD was prepared using hydrothermal method. Cell culture study and In vivo assessments on C57BL/6 mice containing melanoma cancer cells was performed. Results Results showed that CQD size slightly enhanced from 24.55 nm to 42.67 nm after ICG loading. Detection of reactive oxygen species (ROS) demonstrated that CQD improved ICG photo-stability and ROS generation capacity upon laser irradiation. Cell culture study illustrated that ICG@CQD could decrease survival rate of melanoma cancer cells of B16F10 cell line from 48% for pure ICG to 28% for ICG@CQD. Confocal microscopy images approved more cellular uptake and more qualified cell imaging ability of ICG@CQD. In vivo assessments displayed obvious inhibitory effect of tumor growth for ICG@CQD in comparison to free ICG on the C57BL/6 mice. In vivo fluorescence images confirmed that ICG@CQD accumulates remarkably more than free ICG in tumor region. Finally, ICG@CQD was proposed as an innovative nanocarrier for PDT and diagnosis.

Bismuth selenide nanoparticles enhance radiation sensitivity in colon cancer cells in-vitro

BackgroundRadiotherapy is one of the primary treatments for cancer, but it can cause damage to normal tissues and lead to side effects. The use of radiosensitizers can enhance the sensitivity of cancer cells to radiation, thereby reducing the amount of radiation required and minimizing damage to healthy tissues. Bismuth selenide nanoparticles (Bi2Se3 NPs) have been shown to have potential as radiosensitizers. Materials and methodsIn this study, we investigated the potential of Bi2Se3 NPs as a radiosensitizer in colon cancer cells (HCT-116) in vitro. The cells were treated with various concentrations of Bi2Se3 NPs and then exposed to ionizing radiation. The viability of the cells was assessed using the MTT assay, and the survival rate was evaluated. ResultsOur results showed that Bi2Se3 NPs significantly enhanced the sensitivity of colon cancer cells to ionizing radiation in a dose-dependent manner. The combination of Bi2Se3 NPs and radiation resulted in a significant decrease in cell viability and survival rate compared to radiation alone. ConclusionBi2Se3 NPs have the potential to be used as a radiosensitizer in the treatment of colon cancer. The findings of this study suggest that combining Bi2Se3 NPs with radiation may enhance the effectiveness of radiotherapy and reduce the mortality rate associated with colon cancer. Further studies are needed to investigate the safety and efficacy of this approach in vivo.

Pristimerin enhances cisplatin-induced apoptosis in nasopharyngeal carcinoma cells via ROS-mediated deactivation of the PI3K/AKT signaling pathway

To explore the effect of pristimerin combined with cisplatin on proliferation and apoptosis of nasopharyngeal carcinoma cells. CCK-8 assay was used to examine the survival rate of HNE-1 and CNE-2Z cells following treatment for 24 h with different concentrations of pristimerin, cisplatin or their combination. The changes in colony formation ability, apoptosis, and intracellular reactive oxygen species (ROS) levels of the treated cells were analyzed using colony formation assay and flow cytometry. Western blotting was performed to detect the changes in protein expressions in the cells. The effects of pre-treatment with NAC on proliferation, apoptosis, and PI3K/AKT signaling pathway were observed in pristimerin- and/or cisplatin-treated cells. Both pristimerin and cisplatin significantly lowered the survival rate of HNE-1 and CNE-2Z cells (P < 0.05). Compared with pristimerin or cisplatin alone, their combination more strongly inhibited survival and colony formation ability of the cells, increased cell apoptosis rate and intracellular ROS levels, upregulated the protein expressions of Bax, cleaved caspase-3, and cleaved PARP, and downregulated the protein expressions of Bcl-2, Mcl-1, PARP and p-PI3K and p-AKT (P < 0.05). NAC pretreatment significantly attenuated proliferation inhibition and apoptosis-promoting effects of pristimerin combined with cisplatin, and partially restored the downregulated protein expressions of p-PI3K and p-AKT in HNE-1 and CNE-2Z cells with the combined treatment (P < 0.05). Pristimerin can enhance cisplatin-induced proliferation inhibition and apoptosis in nasopharyngeal carcinoma cells, the mechanism of which may involve ROS-mediated deactivation of the PI3K/AKT signaling pathway.

Triterpenes from antler-shaped fruiting body of Ganoderma lucidum and their hepatoprotective activities

Seven previously undescribed triterpenes (1–7), as well as one triterpene (8) previously described as a synthetic product, were isolated from the antler-shaped fruiting body of Ganoderma lucidum. Their structures were established based on comprehensive spectroscopy analysis. At a concentration of 10 μM, (24E)-3-oxo-15α-acetoxy-lanosta-7,9(11),24-trien-26-al (3) and (24R,25S)-3-oxo-lanosta-7,9(11)-dien-25-ethoxyl-24,26-diol (5) provided significant protection against acetaminophen-induced necrosis in human HepG2 liver cancer cells, and the cell survival rates were 69.7 and 76.1% respectively, similar to that of the positive control (glutathione, 72.1%). Based on the present results, these compounds could be potential hepatoprotective agents.

Molecular mechanism of Chang Shen Hua volatile oil modulating brain cAMP-PKA-CREB pathway to improve depression-like behavior in rats

BackgroundDepression is a common and complex mental illness that manifests as persistent episodes of sadness, loss of interest, and decreased energy, which might lead to self-harm and suicide in severe cases. Reportedly, depression affects 3.8 % of the world's population and has been listed as one of the major global public health concerns. In recent years, aromatherapy has been widely used as an alternative and complementary therapy in the prevention and treatment of depression; people can relieve anxiety and depression by sniffing plant aromatic essential oils. Acorus tatarinowii and Panax ginseng essential oils in Chang Shen Hua volatile oil (CSHVO) are derived from Acorus tatarinowii and Panax ginseng, respectively, the main medicines in the famous Chinese medicine prescription Kai Xin San (KXS), Then, these oils are combined with the essential oil of Albizia julibrissin flower to form a new Chinese medicine inhalation preparation, CSHVO. KXS has been widely used in the treatment of depression; however, whether CSHVO can ameliorate depression-like behavior, its pharmacological effects, and the underlying mechanisms of action are yet to be elucidated. Study design and MethodsA rat model of chronic and unpredictable mild stimulation (CUMS) combined with orphan rearing was treated with CSHVO for 4 weeks. Using behavioral tests (sucrose preference, force swimming, tail suspension, and open field), the depression-like degree was evaluated. Concurrently, brain homogenate and serum biochemistry were analyzed to assess the changes in the neurotransmitters and inflammatory and neurotrophic factors. Furthermore, tissue samples were collected for histological and protein analyses. In addition, network pharmacology and molecular docking analyses of the major active compounds, potential therapeutic targets, and intervention pathways predicted a role of CSHVO in depression relief. Subsequently, these predictions were confirmed by in vitro experiments using a corticosterone (CORT)-induced PC12 cell damage model. ResultsCSHVO inhalation can effectively improve the weight and depression-like behavior of depressed rats and regulate the expression of inflammatory factors and neurotransmitters. Hematoxylin-eosin, Nissl, and immunofluorescence staining indicated that compared to the model group, the pathological damage to the brain tissues of rats in the CSHVO groups was improved. The network pharmacological analysis revealed that 144 CSHVO active compounds mediate 71 targets relevant to depression treatment, most of which are rich in the cAMP signaling and inflammatory cytokine pathways. Protein-protein interaction analysis showed that TNF, IL6, and AKT are the core anti-depressive targets of CSHVO. Molecular docking analysis showed an adequate binding between the active ingredients and the key targets. In vitro experiments showed that compared to the model group, the survival rate of PC12 cells induced by CSHVO intervention was increased, the apoptosis rate was decreased, and the expression of inflammatory cytokines in the cell supernatant was improved. Western blot analysis and immunofluorescence staining confirmed that CSHVO regulates PC12 cells in the CORT model through the cAMP-PKA-CREB signaling pathway, and pretreatment with PKA blocker H89 eliminates the protective effect of CSHVO on CORT-induced PC12 cells. ConclusionsCSHVO improves CORT-induced injury in the PC12 cell model and CUMS combined with orphan rearing-induced depression model in rats. The antidepressant mechanism of CSHVO is associated with the modulation of the cAMP-PKA-CREB signaling pathway.

MicroRNA-671-5p regulates the inflammatory response of periodontal ligament stem cells via the DUSP8/p38 MAPK pathway.

MicroRNAs are differentially expressed in periodontitis tissues. They are involved in cellular responses to inflammation and can be used as markers for diagnosing periodontitis. Microarray analysis showed that the expression level of microRNA-671-5p in periodontal tissues of patients with periodontitis was increased. In this study, we investigated the mechanism of action of microRNA-671-5p in human periodontal ligament stem cells (hPDLSCs) under inflammatory conditions. HPDLSCs were treated with lipopolysaccharide (LPS) to establish an inflammation model. The cell survival rate was determined using the cell counting kit-8 (CCK8). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot analyses were used to detect the expression of microRNA-671-5p and dual-specificity phosphatase (DUSP) 8 proteins, respectively, Interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α were detected using qRT-PCR and Enzyme-linked immunosorbent assay (ELISA). A dual-luciferase reporter system was employed to determine the relationship between micoRNA-671-5p and DUSP8 expression. Activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway was confirmed using western blot analysis. Following the treatment of hPDLSCs with LPS, the expression levels of microRNA-671-5p in hPDLSCs were increased, cell viability decreased, and the expression of inflammatory factors displayed an increasing trend. MicroRNA-671-5p targets and binds to DUSP8. Silencing microRNA-671-5p or overexpressing DUSP8 can improve cell survival rate and reduce inflammatory responses. When DUSP8 was overexpressed, the expression of p-p38 was reduced. microRNA-671-5p targets DUSP8/p38 MAPK pathway to regulate LPS-induced proliferation and inflammation in hPDLSCs.

Unlocking the antiviral potential of rosmarinic acid against chikungunya virus via IL-17 signaling pathway.

The Chikungunya virus is an Alphavirus that belongs to the Togaviridae family and is primarily transmitted by mosquitoes. It causes acute infection characterized by fever, headache, and arthralgia. Some patients also experience persistent chronic osteoarthritis-like symptoms. Dedicated antiviral treatments are currently unavailable for CHIKV. This study aims to explore the potential anti-CHIKV effect of rosmarinic acid using network pharmacology. This study employed network pharmacology to predict and verify the molecular targets and pathways associated with ROSA in the context of CHIKV. The analysis outcomes were further validated using molecular docking and in vitro experiments. The analysis of CHIKV targets using the Kyoto Encyclopedia of Genes and Genomes and MCODE identified IL-17 as an important pathogenic pathway in CHIKV infection. Among the 30 targets of ROSA against CHIKV, nearly half were found to be involved in the IL-17 signaling pathway. This suggests that ROSA may help the host in resisting CHIKV invasion by modulating this pathway. Molecular docking validation results showed that ROSA can stably bind to 10 core targets out of the 30 identified targets. In an in vitro CHIKV infection model developed using 293T cells, treatment with 60 μM ROSA significantly improved the survival rate of infected cells, inhibited 50% CHIKV proliferation after CHIKV infection, and reduced the expression of TNF-α in the IL-17 signaling pathway. This study provides the first confirmation of the efficacy of ROSA in suppressing CHIKV infection through the IL-17 signaling pathway. The findings warrant further investigation to facilitate the development of ROSA as a potential treatment for CHIKV infection.