Apoptosis Signaling Pathways Research Articles

The anti-tumor effects of main component (benzethonium chloride) of butorphanol tartrate injection in non-small cell lung cancer

Cancer is one of the leading causes of morbidity and mortality in the global population. The effective management of cancer-associated pain and anesthesia are critical aspects of comprehensive cancer treatment. However, the role and mechanism of anesthesia and analgesia-related drugs in tumors remain controversial. In this study, the efficacy of 16 commonly used analgesics and anesthetics against non-small cell lung cancer (NSCLC) was evaluated. Among the 16 examined injections, butorphanol tartrate injection significantly inhibited the proliferation of NSCLC cells and increased the sensitivity of the EGFR-TKI-resistant H1975 cell line to gefitinib. Benzethonium chloride (BC) is the main active antitumor ingredient of butorphanol tartrate injection. BC may regulate the cell cycle, apoptosis and EMT signaling pathways by modulating the P53 signaling pathway. Our study reveals the therapeutic value of butorphanol tartrate injection and BC in the treatment of NSCLC and provides a theoretical basis for comprehensive therapies for NSCLC.

Thiazolidinedione derivatives in cancer therapy: exploring novel mechanisms, therapeutic potentials, and future horizons in oncology.

Thiazolidinedione derivatives have shown significant potential as targeted cancer therapies by leveraging their various mechanisms of action. These include suppressing cell proliferation, triggering apoptosis, and influencing signaling pathways associated with tumor development. Their multifaceted effects make them promising candidates for advancing cancer treatment strategies. They have shown significant promise as anti-cancer agents, particularly through their ability to inhibit lipogenesis pathways and apoptosis essential for cancer cell survival and proliferation. This review comprehensively examines the anti-cancer potential of thiazolidinedione derivatives by targeting key aspects of lipid metabolism, apoptosis, and various mechanistic pathways. This review provides an in-depth examination of the anti-cancer potential of TZD derivatives, focusing on their mechanisms of action, therapeutic applications, and future directions in oncology. The anti-tumor effects of TZDs primarily involve the stimulation of peroxisome proliferator-activated receptor gamma (PPAR-γ), suppressing cell proliferation, induction of apoptosis, and inhibition of angiogenesis. Moreover, recent evidence highlights their ability to modulate non-PPAR-γ pathways, such as PI3K/Akt, NF-κB, and MAPK, further expanding their role in overcoming drug resistance and enhancing therapeutic outcomes. This review explores the preclinical (in vitro and in vivo) and clinical research investigating TZD derivatives efficacy in various cancer types. The insights underscore the significance of targeting lipogenesis as a novel anti-cancer strategy, positioning thiazolidinedione derivatives as potent candidates for future cancer therapeutics. As the oncology landscape evolves, TZD derivatives (rosiglitazone, pioglitazone, inolitazone, troglitazone, and 2,4-thiazolidinedione derivatives) represent a promising class of agents with the potential to contribute meaningfully to cancer treatment. By integrating existing knowledge with recent advancements, this study provides valuable insights into the role of thiazolidinedione derivatives in cancer treatment, paving the way for further research and clinical applications.

TRIM3 modulates cisplmatin-resistant of cervical squamous cell carcinoma via endoplasmic reticulum stress signaling in vitro.

TRIM3 is widely recognized as a tumor suppressor gene. However, its precise role in cervical squamous cell carcinoma (CESC) remains elusive. Here, we observed a significant decrease in the expression of TRIM3 in CESC cells. Overexpression of TRIM3 suppresses cell proliferation and clonal formation. Through the establishment of cisplatin (cDDP)-resistant CESC cell lines, we discovered that the expression of TRIM3 was further downregulated in cDDP-resistant cells, while overexpression of TRIM3 enhanced cellular sensitivity to cDDP. Mechanistic investigations revealed that TRIM3 directly interacts with GRP78, a crucial protein involved in endoplasmic reticulum stress (ERS) pathway, promoting its ubiquitination degradation. Under cDDP treatment, the overexpression of TRIM3 in cDDP-resistant cells suppressed cell proliferation and downregulated the expression of drug-resistant genes, while simultaneously enhancing the activation of apoptosis signaling pathways. However, co-expression of TRIM3 and GRP78 restored cellular sensitivity to cDDP back to normal levels. Consequently, overexpressing TRIM3 in drug-resistant cells facilitates PERK activation and subsequent induction of apoptosis through inhibition of GRP78, ultimately suppressing drug resistance and inducing apoptosis in CESC cells. In conclution, our study suggests that the TRIM3/GRP78 axis regulates cDDP resistance in CESC cells by modulating the downstream apoptotic pathway of ERS.

Deciphering the Underlying Mechanisms of Sanleng-Ezhu for the Treatment of Idiopathic Pulmonary Fibrosis Based on Network Pharmacology and Single-cell RNA Sequencing Data.

To decipher the underlying mechanisms of Sanleng-Ezhu for the treatment of idiopathic pulmonary fibrosis based on network pharmacology and single-cell RNA sequencing data. Idiopathic Pulmonary Fibrosis (IPF) is the most common type of interstitial lung disease. Although the combination of herbs Sanleng (SL) and Ezhu (EZ) has shown reliable efficacy in the management of IPF, its underlying mechanisms remain unknown. Based on LC-MS/MS analysis and the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, we identified the bioactive components of SL-EZ. After obtaining the IPF-related dataset GSE53845 from the Gene Expression Omnibus (GEO) database, we performed the differential expression analysis and the weighted gene co-expression network analysis (WGCNA), respectively. We obtained lowly and highly expressed IPF subtype gene sets by comparing Differentially Expressed Genes (DEGs) with the most significantly negatively and positively related IPF modules in WGCNA. Subsequently, we performed Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on IPF subtype gene sets. The low- and highexpression MCODE subgroup feature genes were identified by the MCODE plug-in and were adopted for Disease Ontology (DO), GO, and KEGG enrichment analyses. Next, we performed the immune cell infiltration analysis of the MCODE subgroup feature genes. Single-cell RNA sequencing analysis demonstrated the cell types which expressed different MCODE subgroup feature genes. Molecular docking and animal experiments validated the effectiveness of SL-EZ in delaying the progression of pulmonary fibrosis. We obtained 5 bioactive components of SL-EZ as well as their corresponding 66 candidate targets. After normalizing the samples of the GSE53845 dataset from the GEO database source, we obtained 1907 DEGs of IPF. Next, we performed a WGCNA analysis on the dataset and got 11 modules. Notably, we obtained 2 IPF subgroups by contrasting the most significantly up- and down-regulated modular genes in IPF with DEGs, respectively. The different IPF subgroups were compared with drugcandidate targets to obtain direct targets of action. After constructing the protein interaction networks between IPF subgroup genes and drug candidate targets, we applied the MCODE plug-in to filter the highest-scoring MCODE components. DO, GO, and KEGG enrichment analyses were applied to drug targets, IPF subgroup genes, and MCODE component signature genes. In addition, we downloaded the single-cell dataset GSE157376 from the GEO database. By performing quality control and dimensionality reduction, we clustered the scattered primary sample cells into 11 clusters and annotated them into 2 cell subtypes. Drug sensitivity analysis suggested that SL-EZ acts on different cell subtypes in IPF subgroups. Molecular docking revealed the mode of interaction between targets and their corresponding components. Animal experiments confirmed the efficacy of SL-EZ. We found SL-EZ acted on epithelial cells mainly through the calcium signaling pathway in the lowly-expressed IPF subtype, while in the highly-expressed IPF subtype, SL-EZ acted on smooth muscle cells mainly through the viral infection, apoptosis, and p53 signaling pathway.

In vitro and in vivo studies of a decanuclear Ni(II) complex as a potential anti-breast cancer agent

A non-platinum-metal decanuclear complex [Ni10L4(CH3COO)8 (C2H5OH)8]·8(C2H5OH) (Ni10 complex) has been developed with a tri-dentate 2,3-dihydroxybenzaldehyde-2-aminophenol Schiff base ligand (H3L). Single crystal X-ray analysis reveals that the Ni10 complex displays a sandwich loaf-shaped decanuclear structure and its anticancer activity was evaluated. The cell cytotoxicity results indicating that the Ni10 complex is most effective to human breast cancer cells MDA-MB-231 and its mechanism were further investigated. Flow cytometry analysis showed that the Ni10 complex triggered cell cycle arrest and induced apoptosis of MDA-MB-231 cells. Western blot analysis of the changes of intracellular protein expression showed that Ni10 triggers MDA-MB-231 apoptosis through mitochondrial mediated apoptosis signaling pathways. In vivo experiments showed that the Ni10 complex significantly suppressed breast tumor growth with low toxicity against major organs in a nude mice model. The good treatment effect, low toxicity and pharmacological mechanisms of the decanuclear NiII complex may provide a clue for the research and development of non-platinum multinuclear based chemotherapeutic drugs.

Multi-omics revealed activation of TNF-α induced apoptosis signaling pathway in testis of DEHP treated prepubertal male rat

Di-(2-ethylhexyl) phthalate (DEHP) exposure has been associated with male reproductive damage, but the mechanisms involved remain incompletely defined. This study aims to investigate the effects of DEHP exposure on the testes of prepubertal rats through an integrative analysis of metabolomics and transcriptomics, combined with molecular experiments. DEHP exposure resulted in decreased testis weight and increased oxidative stress level in the testis tissues of prepubertal male rats. Moreover, our findings showed a disordered testis structure, reduced spermatogenic and Sertoli cells as well as destruction of mitochondria structure in the testis tissues of DEHP-treated prepubertal male rats. Transcriptome function analysis together with metabolome function analysis indicated that spermatogenesis, apoptosis, inflammatory, lipid metabolism as well as DNA repair signaling pathway were enriched in the testis of DEHP-treated prepubertal male rats. The integrative omics analysis further suggested that TNF-α induced apoptosis played a crucial role in mediating the detrimental effects of DEHP exposure on the testis of prepubertal rats, which was validated by ELISA, Western blotting and Tunel assays. Validation experiments conducted in vitro using GC-2 cells corroborated these findings, demonstrating that mono-(2-ethylhexyl) phthalate (MEHP), the main active metabolite of DEHP, significantly inhibits cell proliferation and increases apoptosis via activating the TNF-α apoptosis pathway. Overall, these findings provided a novel mechanism of dysregulated spermatogenesis of DEHP exposure on the testes of prepubertal rats.

Mechanism of melanoma suppression by Prosopis juliflora derived alkaloids: Apoptosis induction and signaling pathway inhibition

BackgroundTraditional medicines remain integral to healthcare worldwide especially in developing countries. Our prior studies highlighted the anti-melanoma potential of Prosopis juliflora leave methanolic extract (PJLME), leading us to further isolate and characterize bioactive compounds from PJLME and evaluate their efficacy against melanoma. In this context, we identified alkaloid fractions derived from PJLME (PJLME-AF) as key agents in PJLME's cytotoxic effect against melanoma cells. PurposeThe purpose of this research was to evaluate the anti-cancer effects and mechanisms of PJLME-AF on melanoma cell lines. MethodsChemical Profiling of PJLME-AF was conducted by using LC-ESI-MS/MS. Cell viability and anti-migratory effects of PJLME-AF were assessed through MTT, wound healing and transwell assays. Mechanistic study of PJLME-AF was explored using ROS generation assay, apoptosis assays (Annexin V) assay, western blot (apoptotic protein, EMT markers, stem cell markers and signalling pathways), qPCR. In-vitro spheroid assay was performed to explored the PJLME-AF cytotoxic effects on tumour spheroid forming ability of melanoma cells. Additionally, the anti-tumor efficacy of PJLME-AF was tested in an in-vivo C57BL/6 mouse model. ResultsPJLME-AF demonstrated potent anti-proliferative, anti-migratory and anti-invasive effects on melanoma cells. Mechanistic study indicates that PJLME-AF strongly induce ROS generation and subsequent apoptotic cell death in melanoma cells. Furthermore, PJLME-AF downregulated epithelial-to-mesenchymal transition (EMT) proteins, stem cell markers and Akt/Erk cell survival proteins providing insights into its molecular mechanisms. Notably, PJLME-AF inhibited spheroid formation and reduced PD-L1 expression. Finally, anti-tumor activity of PJLME-AF was further confirmed in a in-vivo mice model. Additionally, PJLME-AF combined with dacarbazine, exhibited enhanced cytotoxicity on melanoma compared to the drug alone. ConclusionPJLME-AF exhibit promising natural anti-cancer agents for metastatic melanoma treatment. This research contributes to the development of novel, safe, and cost-effective agents for metastatic melanoma treatment and as a potential candidate for further cancer research.

Studies on the Role of MAP4K2, SPI1, and CTSD in Osteoporosis.

Osteoporosis (OP) is a prevalent skeletal disorder characterized by an imbalance between bone resorption and bone formation, resulting in a significant global burden. Previous research utilizing bioinformatics analysis has identified MAP4K2, SPI1, and CTSD as hub genes associated with OP. In this current investigation, we have successfully established a differential expression system of MAP4K2, SPI1, and CTSD in rat bone marrow mesenchymal stem cells (BMSCs) through transfection techniques. Additionally, the CCK-8 assay was employed to assess cell proliferation, while the alkaline phosphatase (ALP) activity assay and ALP staining assay were utilized to evaluate osteogenic differentiation. Alizarin red staining was employed to detect mineralization of BMSCs. Furthermore, the expression of relevant genes and molecules associated with the MAPK signaling pathway, autophagy, and apoptosis in the sera of rat BMSCs were examined using quantitative real-time polymerase chain reaction (qRT-PCR). The purpose of this study was to preliminarily investigate whether MAP4K2, SPI1, and CTSD have an effect on the osteogenic capacity of rat BMSCs and whether these genes, when differentially expressed, affect the expression of related genes in the MAPK, autophagy, and apoptosis signaling pathways and thus the osteogenic function of BMSCs. In summary, the findings of this study indicate that MAP4K2 and CTSD exert significant influence on the proliferation, osteogenic differentiation, and mineralization processes of rat BMSCs cells. Furthermore, these proteins may contribute to the development of OP through their involvement in the regulation of autophagy and apoptosis. Conversely, our investigation did not reveal any discernible impact of SPI1 on OP-related phenotypes. Consequently, this research serves as a fundamental basis for further exploration of potential therapeutic targets for the treatment of OP.

Effect of Caffeic Acid and a Static Magnetic Field on Human Fibroblasts at the Molecular Level - Next-generation Sequencing Analysis.

Due to their properties, numerous polyphenols and a static magnetic field could have therapeutic potential. Therefore, the aim of our research was to investigate the effect of caffeic acid (CA), a moderate-strength static magnetic field (SMF) and their simultaneous action on human fibroblasts in order to determine the molecular pathways they affect, which might contribute to their potential use in therapeutic strategies. The research was conducted using normal human dermal fibroblasts (NHDF cells) that had been treated with caffeic acid at a concentration of 1 mmol/L and then exposed to a moderate-strength static magnetic field. The RNA that had been extracted from the collected cells was used as a template for next-generation sequencing (NGS) and an RT-qPCR reaction. We identified a total of 1,006 differentially expressed genes between CA-treated and control cells. Exposure of cells to a SMF altered the expression of only 99 genes. Simultaneous exposure to both factors affected the expression of 953 genes. It has also been shown that these genes mainly participate in cellular processes, including apoptosis. The highest fold change value were observed for HSPA6 and HSPA7 genes. In conclusion, the results of our research enabled the modulators, primarily caffeic acid and to a lesser extent a static magnetic field, of the apoptosis signaling pathway in human fibroblasts to be identified and to propose a mechanism of their action, which might be useful in the development of new preventive and/or therapeutic strategies. However, more research using other cell lines is needed including cancer cells.

HSP60 inhibits DF-1 apoptosis through its mitochondrial signal peptide

HSP60 is implicated in many biological functions and plays a key role in maintaining oxidative stress and preserving mitochondrial integrity. Our previous study showed that HSP60 inhibits apoptosis. In this study, we further investigated the mechanism of apoptosis inhibition by HSP60. First, the CRISPR-Cas9 system was employed to establish the HSP60 knockout DF-1 cell line (DF-1-HSP60-KO), and the apoptosis level of DF-1-HSP60-KO cell line was assessed by flow cytometry and ELISA apoptosis kit. Then, the effect of knockdout of HSP60 on relevant apoptotic factors was assessed by Western blotting and RT-PCR analysis. The results showed that compared with the control DF-1 cells, HSP60 knockdout cells indicated significantly increased apoptosis rates, decreased Bax expression, and enhanced Caspase 3 expression. This suggests that the HSP60 knockout induces apoptosis by up-regulating Caspase 3 and down-regulating Bax expression. The structure of the HSP60 mitochondrial signal peptide (MIT) protein was predicted using Pymol software, which revealed that His amino acid at the 21st position affects its spatial structure. In addition, the transfection of HSP60 mutant protein (TB) into DF-1-HSP60-KO cells and induction with Bardoxolone MethyI significantly increased the apoptosis rates and reduced cell viability compared to the wild-type HSP60 group, inducing differential changes in genes such as Bax, Bak, and Bcl-2. Together, these findings suggest that the HSP60 MIT's His amino acid at site 21 modulates the levels of genes associated with the apoptosis signaling pathway, thereby inhibiting apoptosis. This study reveals the regulatory role of HSP60 in apoptosis through its mitochondrial signal peptide, which will have potential medical value.

Effect of stem extract of Schisandra Chinensis on improving spermatogenesis disorder induced by Cisplatin in Vivo and in Vitro

BackgroundThe primary adverse effect of chemotherapy drugs is the induction of spermatogenic disorders. Schisandra chinensis (Turcz) Baill. have been preliminarily shown to have a significant ameliorative in spermatogenic disorders. Nevertheless, there are relatively few studies on non-medicinal parts such as stems of S. chinensis, which have good therapeutic potential for side effects caused by cisplatin. Up to now, a total of 238 compounds have been isolated and identified from the vine stem of S. chinensi. The main components are lignans, polysaccharides, volatile oils, and organic acids. Therefore, the development of S. chinensis stem as a source of a novel chemotherapy drug protector is of great significance. MethodsIn the present study, we explored the protective effect of the stem extract of S. chinensis (SCE) against cisplatin-induced spermatogenic disorders and its possible molecular mechanisms in vitro and in vivo. The network pharmacology was used to predict the targets that may act on spermatogenic disorders. Mice were injected intraperitoneally with cisplatin at 2 mg/kg for 7 days to induce spermatogenic disorders. SCE (75, 150, and 300 mg/kg) was administered to mice by gavage for 21 days. TM3 cells were treated with Schisandrol B (Sol B) (0.5, 1, and 2 µM) in the presence or absence of cisplatin (40 µM), and then cell viability, oxidative stress, apoptosis, and mitochondrial function were evaluated. Results16 constituents and target proteins were predicted to have possible effects on spermatogenic disorders by network pharmacology. Both in vivo and in vitro experiments showed a favorable protective effect of SCE against cisplatin-induced spermatogenic disorders. Sol B might as the major chemical component is responsibility for the protective effect. The mechanism may involve the regulation of Nrf2\\HO-1 protein, PI3K\\Akt, apoptosis, and MAPK signaling pathway to modulate 17βHSD, cycp450, Star and other crucial proteins in the testosterone synthesis pathway. Ultimately, this regulatory process aims to ameliorate the disruption of sex hormone secretion by cisplatin. ConclusionThese results indicated that the lignans in SCE could effectively improve the spermatogenesis barrier caused by cisplatin. These findings provided a theoretical basis for the development of non-medicinal parts of S. chinensis, and laid a foundation for improving spermatogenesis disorders caused by chemotherapy drugs.

Green hydrothermal synthesis of gallic acid carbon dots: characterization and cytotoxic effects on colorectal cancer cell line

Colorectal cancer (CRC) remains a leading cause of cancer-related deaths worldwide, necessitating the development of novel therapeutic approaches. Carbon dots (CDs) have emerged as promising nanoparticles for biomedical applications due to their unique properties. Gallic acid (GA), an anticancer agent, is effective against various tumor types. This study explores the potential of gallic acid-derived carbon dots (GA-CDs) as an innovative anticancer agent against HCT-116 CRC cells, focusing on apoptosis signaling pathways. GA-CDs were synthesized using a one-pot hydrothermal method. Characterization was conducted using transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy, and ultraviolet-visible (UV-vis) absorption spectroscopy. The cytotoxicity of GA and GA-CDs on HCT-116 cells was evaluated using the MTT assay at various concentrations over 24 and 48 h. Cellular uptake was assessed via fluorescence microscopy, and apoptosis was analyzed using acridine orange/propidium iodide (AO/PI) staining. Total RNA extraction followed by complementary DNA (cDNA) synthesis via reverse transcription-PCR was performed, and real time-PCR (Q-PCR) was conducted to examine the expression of apoptosis-related genes includingCaspase-3,Bax, andBcl-2. Characterization confirmed the successful synthesis of spherical GA-CDs. GA-CDs exhibited dose- and time-dependent cytotoxicity, with IC50 values of 88.55 μg ml-1for GA-CDs and 192.2 μg ml-1for GA after 24 h. Fluorescence microscopy confirmed the efficient uptake of GA-CDs by HCT-116 cells. AO/PI staining showed a significant increase in apoptotic cell numbers after treatment with GA-CDs. Q-PCR analysis revealed overexpression ofCaspase-3 andBaxgenes in GA-CD-treated cells, though no significant changes were observed in the expression ofBcl-2 or theBax/Bcl-2 ratio. GA-CDs demonstrated potent anticancer properties by inducing apoptosis and reducing cell viability in HCT-116 cells. These findings suggest the potential of GA-CDs as a novel therapeutic agent for CRC treatment, warranting further investigation into their mechanism of action andin vivoefficacy.

Integrating multi-level interactive network analysis and in vivo studies to explore the protective mechanism of Maillard products of skipjack trypsin hydrolysate in hyperuricemia

This study used skipjack by-products to produce skipjack trypsin hydrolysate (STH), which was then processed through the Maillard reaction to create its Maillard product, STHMS3 (200–1000 Da). We evaluated STHMS3's protective effects against hyperuricemia-induced renal injury in mice. Utilizing in vivo experiments, network pharmacology, and molecular docking, we explored its protective mechanisms. STHMS3 significantly decreased serum uric acid, creatinine, blood urea nitrogen, and xanthine oxidase (XOD) levels, reduced oxidative stress, and enhanced antioxidant protein levels in kidneys. Network pharmacology analysis showed STHMS3's interaction with multiple targets and pathways, including apoptosis, NF-κB, and TNF signaling pathways, suggesting a multi-level interactive network mechanism. Molecular docking confirmed STHMS3's ability to directly inhibit XOD through hydrogen bond formation. This study highlights the therapeutic potential of food-derived peptides in managing hyperuricemia and protecting renal function.

FUT8 upregulates CD36 and its core fucosylation to accelerate pericyte-myofibroblast transition through the mitochondrial-dependent apoptosis pathway during AKI-CKD

BackgroundActivation of pericytes leads to renal interstitial fibrosis, but the regulatory mechanism of pericytes in the progression from AKI to CKD remains poorly understood. CD36 activation plays a role in the progression of CKD. However, the significance of CD36 during AKI-CKD, especially in pericyte, remains to be fully defined.MethodsGEO and DISCO database were used to analyze the expression of CD36 in pericyte during AKI-CKD; IRI to conduct AKI-CKD mouse model; Hypoxia/Reoxygenation (H/R) to induce the cell model; RT-qPCR and Western blotting to detect gene expression; IP and confocal-IF to determine the core fucosylation (CF) level of CD36. Flow cytometry (AV/PI staining) to detect the cell apoptosis and JC-1 staining to react to the change of mitochondrial membrane potential.ResultsDuring AKI to CKD progression, CD36 expression in pericytes is higher and may be influenced by CF. Moreover, we confirmed the positive association of CD36 expression with pericyte-myofibroblast transition and the progression of AKI-CKD in an IRI mouse model and hypoxia/reoxygenation (H/R) pericytes. Notably, we discovered that FUT8 upregulates both CD36 expression and its CF level, contributing to the activation of the mitochondrial-dependent apoptosis signaling pathway in pericytes, ultimately leading to the progression of AKI-CKD.ConclusionThese results further identify FUT8 and CD36 as potential targets for the treatment in the progression of AKI-CKD.

Research Progress with Atractylone as an Antitumor Agent.

Atractylone is a sesquiterpenoid compound extracted from Rhizoma Atractylodis. As one of the main active components in the volatile oil of the Atractylodes genus, it has exhibited certain therapeutic effects, including anti-inflammatory, antiviral, antioxidant, antiallergic, antiangiogenic, and neuroprotective activities, among others. With further research on the chemical constituents and pharmacology of sesquiterpenes, research on the antitumor activity of Atractylone has also been further expanded. Much of the current literature pays particular attention to the antitumor activity of Atractylone, which was found to inhibit the apoptosis of tumor cells and prevent growth, invasion, and migration through different apoptosis pathways and signaling pathways. Due to its promising potential for cancer prevention, it may play a role in reducing the incidence of malignant tumors. In this paper, the antitumor activity and mechanism of Atractylone are reviewed, providing a reference to inform future research on the tumor treatment, clinical application, and further development and utilization of this plant genus.

Neurocognitive impairments in rat offspring after maternal exposure to vortioxetine: Involvement of BDNF, apoptosis and cholinergic mediated signaling pathways

Depression in pregnant women raises concerns about the safety of antidepressants use, particularly its impact on offspring’s neurocognition. This study investigates the effects of maternal exposure to vortioxetine (VOX) on the neurocognitive development of rat offspring. Pregnant Wistar rats were administered clinically pertinent doses of VOX, 1 mg/kg/day or 2 mg/kg/day from gestational day 6–21. The dams delivered their offspring naturally and reared until postnatal day (PND) 70. Offspring of both sexes were assessed for postnatal growth by measuring body weight from PND 1–70 weekly and cognitive function using Morris water maze (MWM) test and passive avoidance learning test from PND 49–70. After behavioral assessments, adult rat offspring were sacrificed, and their brains were dissected out for assessment of brain morphology as well as biochemical analysis. The results demonstrated that VOX exposure potentially impaired cognitive performance, evidenced by increased latency in MWM and passive avoidance learning tests. Additionally, it led to decreased body weight, altered brain morphology, and disrupted neurobiochemical profiles. Specifically, VOX 2 mg/kg exposure significantly reduced brain-derived neurotrophic factor (BDNF) expression, increased pro-apoptotic BAX expression, decreased anti-apoptotic Bcl-2 expression, and elevated acetylcholinesterase (AChE) activity in the hippocampus. Lower dose of VOX (1 mg/kg) did not show significant adverse effects on neurocognition, suggesting a dose-dependent impact. No sex specific neurocognitive deficits were observed in current study. These findings indicate that while VOX may offer a safer profile compared to SSRIs, high doses during pregnancy can still result in neurocognitive impairments in offspring.

Pinus massoniana pollen polysaccharides alleviate LPS-induced myocardial injury through p110β-mediated inhibition of the PI3K/AKT/NFκB pathway

The inflammatory response is the core of the pathogenesis of lipopolysaccharide (LPS)-induced sepsis myocardial injury (SMI). Pinus massoniana pollen polysaccharide (PPPS) is a natural polymer with known biological activities, including anti-inflammatory, antioxidant, and antiviral properties. In this study, we aimed to investigate the impact of PPPS on SMI, myocardial enzyme levels, pathological changes, oxidative stress, cell apoptosis, and related signaling pathways in LPS-induced SMI models were observed by hematoxylin-eosin (HE) staining, immunohistochemical (IHC) staining, qPCR, Western blot analysis, with a particular focus on anti-inflammatory effects of PPPS. Animal experiments have shown that PPPS mitigates myocardial tissue injury and suppresses the inflammatory response. In the cellular experiments, PPPS protected H9c2 cells from LPS/adenosine triphosphate (ATP)-induced injury and inflammation. Transcriptome analysis and cardiomyocyte validation revealed that PPPS inhibited activation of the PI3K/PTEN/AKT signaling pathway. Additionally, intervention with the PI3K/PTEN/AKT signaling pathway activator counteracted the anti-inflammatory effects of PPPS. Further investigations indicated that PPPS exerts its anti-inflammatory effects in SMI by enhancing the expression of p110β protein and facilitating its interaction with PTEN, thereby inhibiting activation of the PI3K/AKT/NFκB signaling pathway. These results suggest that PPPS is a promising therapeutic agent for the treatment of SMI.

Anticancer effects of pomegranate-derived peptide PG2 on CDK2 and miRNA-339-5p-mediated apoptosis via extracellular vesicles in acute leukemia

Acute leukemia has rapid onset and severe complications. Anticancer peptides from natural sources have demonstrated efficacy in eliminating various cancers through apoptosis signaling pathways. Additionally, extracellular vesicles containing microRNAs play pivotal roles in promoting tumorigenesis. Therefore, this study aimed to investigate the impact of PG2, a pomegranate peptide that regulates extracellular vesicles, on the induction of acute leukemia cell apoptosis. NB4 and MOLT-4 leukemia cell lines were treated with PG2 alone or in combination with daunorubicin to assess cell viability using the MTT assay. Extracellular vesicles were extracted from PG2-treated NB4 and MOLT-4 cells. Bioinformatic tools were utilized to predict target proteins and microRNAs, following which mRNA and protein expression were determined by using RT‒qPCR and western blotting, respectively. PG2 significantly reduced the viability of NB4 and MOLT-4 cells. Furthermore, the combination of PG2 with daunorubicin had a synergistic effect on NB4 and MOLT-4 cells. Subsequent treatment with PG2 or PG2-treated extracellular vesicles decreased CDK2 expression while increasing microRNA-339-5p and caspase-3 expression in NB4 and MOLT-4 cells. Our findings revealed that the anticancer activity of PG2 through the CDK2/miR-339-5p/caspase-3 pathway is mediated by extracellular vesicles, ultimately inducing apoptosis. PG2 holds promise as a potential antileukemic drug.

Salmon Nasal Cartilage-Derived Proteoglycans Alleviate Monosodium Iodoacetate-Induced Osteoarthritis in Rats.

Osteoarthritis is a chronic inflammatory condition characterized by the degeneration of joint cartilage and underlying bone, resulting in pain, swelling, and reduced mobility. This study evaluates the efficacy of salmon nasal cartilage-derived proteoglycans in mitigating osteoarthritis symptoms and investigates the underlying molecular mechanisms. This study employed a rat model of osteoarthritis induced by monosodium iodoacetate (MIA) injection. The rats were orally administered salmon nasal cartilage-derived proteoglycans or ibuprofen. Key aspects of osteoarthritis pathology, including impaired exercise ability, inflammation, extracellular matrix degradation, and chondrocyte apoptosis, were assessed using histological analysis, micro-CT, treadmill testing, serum assays, and mRNA/protein expression studies. The MIA injection caused significant cartilage damage, reduced bone mineral density, and impaired exercise ability. Additionally, it elevated serum levels of prostaglandin E2 and nitric oxide, increased the mRNA and protein levels of inflammation-related factors, and activated apoptosis signaling pathways in cartilage. Treatment with salmon nasal cartilage-derived proteoglycans significantly improved cartilage morphology and mineralization, reduced inflammation, and inhibited apoptosis signaling pathways, with effects comparable to those observed with ibuprofen treatment. These findings highlight the potential of salmon nasal cartilage-derived proteoglycans as a therapeutic agent for managing osteoarthritis by effectively reducing inflammation, preventing cartilage degradation, and inhibiting chondrocyte apoptosis.

Senescence Gene Senex May Regulate Apoptosis Signaling Pathway, Stem Cell Signaling Activation and Tumor Microenvironment to Promote Tumorigenicity and Invasiveness of Burkitt Lymphoma Cell

Background: The SENEX gene, encoding the protein ARHGAP18, is thought to be involved in the development of various diseases. Previous studies have shown that the SENEX gene may trigger tumor cell senescence and is highly expressed in relapsed and refractory lymphoma. However, the mechanism of action of the SENEX gene in Burkitt's lymphoma remains unclear. Methods: We verified the effect of SENEX gene-induced cellular senescence on RAJI cell through a series of functional experiments, including senescence-associated-β-galactosidase(SA-β-Gal) staining, cell proliferation, apoptosis and Transwell assays. The effects of SENEX gene-triggered senescence on the expression levels of senescence-related proteins, EMT-related proteins and WNT/β-catenin signaling pathway star proteins were detected by Western blot experiments. In addition, we established an immunodefic ient mice model of subcutaneous xenografts to observe the effects of SENEX gene-triggered tumor cell senescencehe biological characteristics and survival of lymphoma in vivo. Results:Chemotherapy-induced SIPS significantly improves the SENEX gene and senescence-associated proteins, promoting resistance to apoptosis and leading to drug resistance. Through in vitro experiments, we found that SENEX gene-mediated SIPS affects the levels of senescence-associated proteins, enhances tumor cell apoptosis resistance, and increases tumor invasiveness via epithelial-mesenchymal transition (EMT) and the WNT/β-catenin pathway. In vivo experiments revealed that both chemotherapy-induced and SENEX gene-mediated SIPS promote malignant growth of mouse xenografts and reduce survival time. The mechanisms involve resistance to apoptosis through cellular senescence, tumor invasion and metastasis promotion via the WNT/β-catenin signaling pathway, and tumor progression through alterations in the tumor microenvironment. Conclusion: Our study reveals that the SENEX gene can regulate the apoptosis signaling pathway, stem cell signaling activation and reprogram the tumor microenvironment to promote tumorigenicity and invasiveness of Burkitt's lymphoma cells both in vitro and in vivo. The SENEX gene may be a potential therapeutic target for Burkitt's lymphoma.