Process Of Apoptosis Research Articles

Apoptosis-associated genetic mechanisms in the transition from rheumatoid arthritis to osteoporosis: A bioinformatics and functional analysis approach.

This study explores the mechanisms of glucocorticoid-induced osteoporosis (OP) and Rheumatoid arthritis (RA), focusing on apoptosis and its role in the progression from RA to OP. Using microarray data from the GEO database, differential gene expression analysis was conducted with the limma package, identifying significant genes in RA and OP. Weighted Gene Co-expression Network Analysis (WGCNA) further examined gene relationships with the disease status, identifying co-expression patterns. Key genes were pinpointed by intersecting differentially expressed genes from RA and OP datasets with WGCNA module genes. Functional enrichment analysis using the "clusterProfiler" package focused on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. Machine learning methods, including Lasso and Random Forest, refined the selection of key genes related to apoptosis. Immune infiltration analysis using CIBERSORT assessed immune cell differences between disease and normal samples. The study highlighted two crucial genes: ATXN2L and MMP14. These genes were identified through various analyses and found to be significantly associated with the progression of RA and OP. Gene Set Enrichment Analysis of ATXN2L and MMP14 revealed their involvement in specific biological processes and pathways. Correlation analysis between these key genes and immune cell infiltration showed significant associations. The ROC analysis evaluated the diagnostic performance of ATXN2L and MMP14, with miRNA regulatory networks related to these genes also predicted. In summary, this research provides valuable insights into the molecular mechanisms of RA and OP, emphasizing the importance of apoptosis and immune processes.

O-GlcNAcylation of hexokinase 2 modulates mitochondrial dynamics and enhances the progression of lung cancer.

Non-small cell lung cancer (NSCLC) stands as the prevailing manifestation of lung cancer, with current therapeutic modalities linked to a dismal prognosis, necessitating further advancements. Hexokinase 2 (HK2), a critical enzyme positioned on the mitochondrial membrane, exerts control over diverse biological pathways, thereby regulating cancer. Nevertheless, the precise role and mechanism of HK2 in NSCLC remain inadequately elucidated, warranting comprehensive investigation. HK2 expression in NSCLC tissues and cell lines was detected through immunohistochemistry and western blot analysis. Concurrently, shRNA assays were applied to scrutinize the impact of HK2 on cell proliferation, apoptosis, migration, and invasion processes in NSCLC cell lines, utilizing CCK8, flow cytometry, wound-healing assay, and transwell techniques. The involvement of HK2 in mitochondrial dynamics was probed through western blot analysis, mitochondrial membrane potential assay, and assessment of ROS generation. Next, the functional role of HK2 was assessed by examining its influence on xenograft tumor growth in nude mice in vivo. Further research has demonstrated that HK2 played a role in NSCLC through its O-GlcNAcylation process. The results of the study revealed that HK2 O-GlcNAcylation promoted the proliferation, migration, and invasive characteristics of NSCLC cells, while alleviating mitochondrial damage, whereas O-GlcNAcylation inactivation yielded the opposite effect. Furthermore, in vivo experiments in nude mice illustrated that HK2 O-GlcNAcylation could stimulate tumor growth in NSCLC. These results suggested that HK2 may impact mitochondrial dynamics in NSCLC through its O-GlcNAcylation, thereby contributing to the progression of NSCLC.

Deficiency of PvDRAM2 increased the nitrite sensitivity of Pacific white shrimp (Penaeus vannamei) by inhibiting autophagy

Autophagy is an essential response mechanism to environmental stress during the evolution of organisms. DRAM2 (Damage-regulated autophagy regulator 2) is recognized as necessary for the process of p53-mediated cell apoptosis. Although the role of DRAM2 in apoptosis has been confirmed, the mechanism of its relationship with autophagy is still unclear. Here we describe PvDRAM2 features and functions. We found that nitrite stress induced autophagy accumulation and ROS production. A novel DRAM-homologous protein, DRAM2, was cloned, and its expression is significantly up-regulated under nitrite stress conditions. PvDRAM2 primarily localizes within the cytoplasmic lysosome.Loss of PvDRAM2 increased sensitivity response to nitrite stress of Pacific white shrimp. And silenced of PvDRAM2 promoted ROS production and inhibited autophagy accumulation. In addition, silenced of PvDRAM2 decreased the autophagy-related protein of p62, Beclin 1, and LC3 expression under nitrite stress of Pacific white shrimp. Collectively, these studies uncover a novel critical role for PvDRAM2 in regulating autophagy under nitrite stress. Specifically, PvDRAM2 is essential for the induction of autophagy, enabling Pacific white shrimp to adapt to environmental stress. This provides mechanistic insight into how autophagy functions as a way for Pacific white shrimp to cope with environmental challenges.

Moderate-intensity training can ameliorate the process of cardiac apoptosis induced by lithium drug consumption in male Wistar rats

Moderate-intensity training can ameliorate the process of cardiac apoptosis induced by lithium drug consumption in male Wistar rats

A lncRNA Transcriptome Analysis of Phycocyanin-Treated Non-Small Cell Lung Cancer A549 Cell Lines

Phycocyanin is a type of marine food additive with multiple biological properties, including anticancer activity, but its underlying antineoplastic mechanism in non-small cell lung cancer (NSCLC) remains unclear. To investigate the underlying regulatory mechanism of phycocyanin in NSCLC, a lncRNA microarray analysis was performed using a phycocyanin-treated A549 cell model. The classification and expression of lncRNAs were determined. The profiles of differentially expressed lncRNAs were generated and analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. The results showed that 193 lncRNAs were upregulated and 116 lncRNAs were downregulated in the phycocyanin-treated group compared with the control group, and qRT‒PCR analysis confirmed the expression of selected lncRNAs. Bioinformatic analysis indicated that the differentially expressed lncRNAs and their target genes were enriched in the extracellular region, epithelium development, NOD-like receptor pathway, Notch signaling, and apoptosis process. In addition, coexpression network analysis identified 2,238 lncRNA‒mRNA, lncRNA‒lncRNA, and mRNA‒mRNA pairs. In particular, 72 etc. differentially expressed lncRNA target genes were discovered in the interaction network, which provides insights into the potential mechanism of phycocyanin in A549 cells. Moreover, cell phenotype experiments showed that downregulating the expression of lncRNA ENST00000538717, a lncRNA that is downregulated after phycocyanin treatment, could significantly inhibit the migration and viability of A549 and H460 cells. In conclusion, this study lays a theoretical and potential foundation for NSCLC treatment and advances our understanding of the regulatory mechanisms of phycocyanin.

Classification of Predictors of Rapid Development of Kidney Failure and Short-Term Changes in Concentration of Circulating Proteins.

Limited knowledge exists regarding short-term changes/increases in concentrations of circulating proteins (referred here as deltas) and rapid development of kidney failure (rapid KF) in diabetes mellitus. Concentrations of 452 circulating proteins were measured by OLINK proteomics platform at baseline and after a median interval of 3-4 years in 106 individuals with type 1 and 77 with type 2 diabetes in two case-control studies. During 10-year follow-up, 31 and 26 individuals, respectively, developed rapid KF. Deltas for 40 proteins predicted rapid KF in both studies. All were better predictors than delta urine albumin-creatinine ratio, and half were better than delta glomerular filtration rate. Comparing the delta proteins with 46 circulating proteins of which elevated baseline concentrations were predictors of rapid KF risk in our previous study, 61 unique proteins were identified. Among these proteins, 21 were good predictors of rapid KF only when measured at baseline (predictors of initiation), 15 were good predictors when measured as deltas (predictors of progression) and 25 were good predictors when both baseline and delta concentrations were used (predictors of initiation and progression). An index score, developed for the latter 25 proteins, provided superior prediction of rapid KF. A subset of these latter proteins was associated with apoptotic processes/tumor necrosis factor (TNF) receptor signaling pathways. Development of rapid KF in diabetes was preceded by elevated concentrations of multiple circulating proteins both at baseline and during short follow-up. Comparing baseline and short-term changes in concentrations of circulating proteins classified predictors of rapid KF risk into those associated with initiation, progression, or both. Predictors of both initiation & progression flagged apoptosis processes and TNF receptor signaling pathways. Multi-protein prognostic algorithms using proteins associated with both initiation and progression improved prediction of rapid KF risk beyond clinical variables.

Disorders in cytokine synthesis in women with uterine fibroids

In the structure of gynecological diseases, uterine fibroids occupy an “honorable” second place after inflammatory processes of the genital organs, and its share reaches 40%. Uterine fibroids are a benign monoclonal tumor that develops from one abnormal smooth muscle cell of the myometrium, which, as a result of mutation, has the ability to grow unregulated. Common symptoms of the disease include pelvic discomfort or pain, excessive uterine bleeding, secondary anemia, infertility, and bowel and bladder dysfunction. Uterine fibroids can negatively affect the general condition of a woman, causing hormonal, vegetative-vascular and psycho-emotional disorders. Moreover, about 80% of patients with uterine fibroids undergo radical surgical treatment. The mechanisms of development and growth of this benign tumor have not been fully established and remain controversial. The role of immune disorders in the pathogenesis of fibroids is currently being discussed. It has been proven that the growth of fibroids is accompanied by a weakening of immune defense against the background of an increase in the level of proinflammatory cytokines, which are regulators of the processes of proliferation and apoptosis, mediators of the action of sex steroids. The aim of the study was to study the level of some pro-inflammatory cytokines (IL-1β, IL-2, TGF-β2 and MCP-1) in the blood serum of women of reproductive age with uterine fibroids, depending on the size and nature of tumor growth. A comparative analysis of the results of examination of 123 women with uterine fibroids, who made up 2 groups: 1st group of 65 women with simple uterine fibroids and 2nd group of 58 women with rapidly growing uterine fibroids, is presented. The examination included a comprehensive clinical and laboratory study. The level of cytokines (IL-1β, IL- 2, TGF-β2, MCP-1) in the blood serum was assessed by ELISA. It was found that in patients of reproductive age with uterine fibroids, there is an increase in the levels of IL-1β, TGF-β2 and MCP-1. In women with rapidly growing uterine fibroids, these changes are more pronounced. The concentration of IL-2 is reduced in all women with uterine fibroids, regardless of the size and nature of tumor growth. It has been established that an increase in the size of myomatous nodes is accompanied by an increase in immune imbalance: there is an increase in the levels of pro-inflammatory cytokines (IL-1β, TGF-β2, MCP-1) against the background of a reduced content of the lymphokine IL-2, which we regard as possible links in the pathogenesis of uterine fibroids. A pronounced deficiency of IL-2 in the blood serum against the background of a sharp increase in the concentration of TGF-β2 and MCP-1 in the blood of women with uterine fibroids can be considered as a negative criterion for predicting disease progression and used as an additional prognostic marker of tumor growth

Evaluation of apoptosis markers in patients with atopic dermatitis

The purpose of the study was to analyze indicators of apoptosis in patients with atopic dermatitis (AD). Patients (N = 88) aged from 12 months to 3 years with varying degrees of disease severity were involved into trial. SCORAD indices were: 68.14±2.63 – in patients with severe AD; 32.03±1.43 – with moderate; and 12.12±1.43 – with mild AD, respectively. Determination of apoptosis markers (Caspase 8, Caspase 9, sCD153, sFas-L, Annexin 5) in blood serum was performed using an enzyme-linked immunosorbent assay (ELISA) using commercial kits from Bender MedSystems® (Austria). A study of apoptosis markers in the blood serum of children with AD revealed a significant decrease (p 0.05) in the concentration of Annexin 5 compared to standard values (by 20 times). A statistically significant decrease (p 0.05) in the concentration levels of Caspase 8 and Caspase 9 in the serum of AD patients was revealed. Thus, the concentrations of Caspase 8 were reduced on by 3 times, and Caspase 9 by 8 times compared to the norm. Also In addition, when determining sFas-L indicators, a statistically significant (p 0.05) decrease in concentration was noted compared to standard indicators. The content of sCD153 in the blood serum in AD patients was significantly higher (p 0.05) than the normative values by 5 times (not detected normally). The most pronounced disturbances in apoptosis indicators were observed in patients with severe atopic dermatitis, (p 0.05), highlighting the importance of studying apoptosis in the context of AD and the possible link between disruptions in this process and the severity of clinical manifestations in patients. The study demonstrates the peculiarities of apoptosis processes in children with AD. On the one hand, these patients have significantly increased activation of signaling systems, on the other hand, the elimination of altered immunocompetent cells does not occur properly, which contributes to the progression and chronicity of immune inflammation in the skin.

Some parameters of the immune system in women with hyperandrogenism

The article is dedicated to studying certain parameters of the immune system, which holds great significance in obstetrics and gynecology. Examining immune system parameters allows for identifying disruptions in reproductive-aged women with hyperandrogenism, which holds crucial practical implications. The authors conducted an immunological study of women with hyperandrogenism and women without this pathology. The aim of the study was to investigate the immune system status in women suffering from hyperandrogenism. Materials and methods of the study: 58 reproductive-aged women diagnosed with hyperandrogenism, under observation at the Women’s Health Center “AyolCare” in Tashkent, were examined. Comprehensive clinical and laboratory examinations were conducted for all women. The control group comprised 35 practically healthy reproductive-aged women. The obtained results indicate that women with altered hormonal balance, including those with hyperandrogenism, experience specific changes in the immune system. The conducted research revealed that the levels of T lymphocytes and T helper/inducer cells decrease, while the number of T killer cells, CD25+ cells (carrying IL-2 receptor), and CD95+ cells (carrying apoptosis signaling receptor) increases. The elevated levels of CD95+ cells indicate increased activation of apoptosis processes, which serve as a protective function of T killer cells. This increase in lymphocyte activation is likely associated with elevated levels of mature activated macrophages and a range of cytokines they produce, which directly stimulate lymphocytes. The detected imbalance in immunological parameters likely indicates that in hyperandrogenism, either the elimination of activated clones of T helper cells is absent or disrupted, which usually leads to the formation of immune response suppression. The increase in the number of activated clones of T lymphocytes is observed in the decreased process of their apoptosis, which is likely intensified by the influence of androgens.

The Role of circRNAs in the Pathological Mechanisms of Alzheimer's Disease and May Serve as Potential Biomarkers.

Alzheimer's disease (AD) is the most common neurodegenerative disease leading to dementia in the elderly, and the mechanisms of AD have not been fully defined. Circular RNAs (circRNAs), covalently closed RNAs produced by reverse splicing, have critical effects in the pathogenesis of AD. CircRNAs participate in production and clearance of Aβ and tau, regulate neuroinflammation, synaptic plasticity and the process of apoptosis and autophagy, indicating that circRNAs may be alternative biomarkers and therapeutic targets. Our review summarizes the functions of circRNAs in the progression and development of AD, which provide insights into the prospect of circRNAs in the diagnosis and treatment of AD.

Circulating proteins linked to apoptosis processes and fast development of end-stage kidney disease in diabetes.

Many circulating proteins are associated with risk of ESKD, but their source and the biological pathways/disease processes they represent are unclear. Using OLINK proteomics platform, concentrations of 455 proteins were measured in plasma specimens obtained at baseline from 399 individuals with diabetes. Elevated concentrations of 46 circulating proteins were associated (P < 1 × 10-5) with development of ESKD (n = 143) during 7-15 years of follow-up. Twenty of these proteins enriched apoptosis/TNF receptor signaling pathways. A subset of 20 proteins (5-7 proteins), summarized as an apoptosis score, together with clinical variables accurately predicted risk of ESKD. Expression of genes encoding the 46 proteins in peripheral WBCs showed no difference between cells from individuals who did or did not develop ESKD. In contrast, plasma concentration of many of the 46 proteins differed by this outcome. In single-nucleus RNA-Seq analysis of kidney biopsies, the majority of genes encoding for the 20 apoptosis/TNF receptor proteins were overexpressed in injured versus healthy proximal tubule cells. Expression of these 20 genes also correlated with the overall index of apoptosis in these cells. Elevated levels of circulating proteins flagging apoptotic processes/TNF receptor signaling pathways - and likely originating from kidney cells, including injured/apoptotic proximal tubular cells - preceded the development of ESKD.

A Selective Melatonin 2 Receptor Agonist, IIK7, Relieves Blue Light-Induced Corneal Damage by Modulating the Process of Autophagy and Apoptosis

This study aims to investigate the effect of the selective MT2 receptor agonist, IIK7, on corneal autophagy and apoptosis, aiming to reduce corneal epithelial damage and inflammation from blue light exposure in mice. Eight-week-old C57BL/6 mice were divided into BL-exposed (BL) and BL-exposed with IIK7 treatment (BL + IIK7 group). Mice underwent blue light exposure (410 nm, 100 J) twice daily with assessments at baseline and on days 3, 7, and 14. Corneal samples were analyzed for MT2 receptor expression, autophagy markers (LC3-II and p62), and apoptosis indicators (BAX expression and TUNEL assay). Then, mice were assigned to normal control, BL, and BL + IIK7. Ocular surface parameters, including corneal fluorescein staining scores, tear volume, and tear film break-up time, were evaluated on days 7 and 14. On day 14, reactive oxygen species (ROS) levels and CD4+ IFN-γ+ T cells percentages were measured. The BL group exhibited higher LC3-II and p62 expression, while the BL + IIK7 group showed reduced expression (p &lt; 0.05). The TUNEL assay showed reduced apoptosis in the BL + IIK7 group compared to the BL group. ROS levels were lower in the BL + IIK7 group. The BL + IIK7 group showed improved ocular surface parameters, including decreased corneal fluorescein staining and increased tear volume. The percentages of CD4+ IFN-γ+ T cells indicated reduced inflammatory responses in the BL + IIK7 group. The MT2 receptor agonist IIK7 regulates corneal autophagy and apoptosis, reducing corneal epithelial damage and inflammation from blue light exposure.

Hybrid Albumin-Decorated Lipid-Nanocarrier-Mediated Delivery of Polyphenol-Rich Sambucus nigra L. in a Potential Multiple Antitumoural Therapy.

The current research attempted to address the suitability of bioactive Sambucus nigra extract entrapped in albumin-decorated nanostructured lipid carriers (NLCs) as a promising "adjuvant" in improving tumour penetration for multiple antitumour therapy. The new hybrid albumin-decorated NLCs were characterised based on, e.g., the particle size, zeta electrokinetic potential, SambucusN entrapment efficiency, and fluorescence spectroscopy and tested for different formulation parameters. The antioxidant activity of NLC-SambucusN was significantly enhanced by a bovine serum albumin (BSA) polymer coating. According to the real-time cell analysis (RTCA) results, NLC-I-SambucusN-BSA behaved similarly to the chemotherapeutic drug, cisplatin, with cell viability for LoVo tumour cells of 21.81 ± 1.18%. The new albumin-NLC-SambucusN arrested cancer cells in G1 and G2 cycles and intensified the apoptosis process in both early and late phases. An advanced induction, over 50% apoptosis in LoVo colon cells, was registered for 50 μg/mL of NLC-II-SambucusN-BSA, a fourfold increase compared to that of untreated cells. RTCA and flow cytometry results showed that concentrations of the hybrid NLC-SambucusN up to 50 μg/mL do not affect the proliferation of normal HUVEC cells. This approach provides insightful information regarding the involvement of phytochemicals in future therapeutic strategies. Albumin-decorated NLCs can be considered a noteworthy strategy to be connected to antitumour therapeutic protocols.

How Do ROS Induce NETosis? Oxidative DNA Damage, DNA Repair, and Chromatin Decondensation.

Neutrophil extracellular traps (NETs) are intricate, DNA-based, web-like structures adorned with cytotoxic proteins. They play a crucial role in antimicrobial defense but are also implicated in autoimmune diseases and tissue injury. The process of NET formation, known as NETosis, is a regulated cell death mechanism that involves the release of these structures and is unique to neutrophils. NETosis is heavily dependent on the production of reactive oxygen species (ROS), which can be generated either through NADPH oxidase (NOX) or mitochondrial pathways, leading to NOX-dependent or NOX-independent NETosis, respectively. Recent research has revealed an intricate interplay between ROS production, DNA repair, and NET formation in different contexts. UV radiation can trigger a combined process of NETosis and apoptosis, known as apoNETosis, driven by mitochondrial ROS and DNA repair. Similarly, in calcium ionophore-induced NETosis, both ROS and DNA repair are key components, but only play a partial role. In the case of bacterial infections, the early stages of DNA repair are pivotal. Interestingly, in serum-free conditions, spontaneous NETosis occurs through NOX-derived ROS, with early-stage DNA repair inhibition halting the process, while late-stage inhibition increases it. The intricate balance between DNA repair processes and ROS production appears to be a critical factor in regulating NET formation, with different pathways being activated depending on the nature of the stimulus. These findings not only deepen our understanding of the mechanisms behind NETosis but also suggest potential therapeutic targets for conditions where NETs contribute to disease pathology.

A modern overview of the process of platelet formation (thrombocytopoiesis) and its dependence on several factors.

Structural and functional alterations in platelets are an actual problem that requires more attention. The treatment of these illnesses proves challenging, inefficient and heavily relies on platelet donations. A difficult task confronting science is producing platelets in vitro, which calls for meticulous examination of factors affecting platelet generation. It is known that megakaryocytes produce platelets in vitro and in vivo differently: in the laboratory we can get a smaller number of platelets compared to the human body. This review primarily examines the stages of megakaryocyte maturation and the processes involved in platelet formation. The article reflects the results of both fundamental research on the problem and the new results obtained over the past decade. Currently, most scientists accept the pro-platelets theory of platelet formation. This review aims to explore in detail each stage of pro-platelet formation and the platelet formation process. It explains on the processes of polyploidization, endomitosis, and apoptosis, as well as the functions of structural cell components (microtubules, mitochondria, T- and α-granules) and pro-platelet migration. The microenvironment influence is acknowledged for the osteoblastic and vascular niches that affect thrombocytopoiesis. The additional aspect is the contribution of specific proteins to thrombocytopoiesis such as RhoA, β1-tubulin, cytokines IL-6, IL-8, Toll-like receptors, etc.

Effect of hypoxia in the post-hatching development of the salmon (Salmo salar L.) spinal cord

IntroductionHypoxia has a teratogenic effect on the fish during embryonic development. Nevertheless, the effects on the larval stage are not yet known. Therefore, the aim of this study was to assess the effects of hypoxia on the number of neurons and their apoptotic rate in the spinal cord of Salmo salar alevins after hatching.MethodsWe used a total of 400 alevins, establishing both hypoxia and control (normoxia) groups (n = 8), considering post-hatching days 1, 3, 5, and 7, each with 50 individuals. Transversal sections of 50 μm thickness were cut from the alevin body. We performed cresyl-violet staining and counted the spinal cord neurons. Also, immunohistochemistry for HIF-1α and caspase-3 were used. For statistical analysis ANOVA one-way and Tukey's Test were used.ResultsHIF-1α was expressed in spinal neurons in both the hypoxic and normoxic groups, with the former being significantly higher. Both the hypoxic and normoxic groups evidenced the process of neuronal apoptosis, with the hypoxic groups demonstrating a higher significance. The number of neurons in the spinal cord was significantly lower in the hypoxic group.DiscussionWe found that when oxygen levels in the aquatic environment were low in Salmo salar farming alevins post-hatch, the number of spinal neurons dropped by half. These results contribute to increasing our knowledge of the biological development of salmon, in particular the genesis of the spinal cord, and the effects of hypoxic conditions on the development of this structure of the nervous system.

Novel dual-color fluorescence probe for monitoring the fluctuation of lysosomal polarity and viscosity during apoptosis

Apoptosis is pivotal in the pathogenesis of cancer and various other diseases. Real-time monitoring of apoptosis is crucial for assessing cell viability and facilitating drug screening. The process of apoptosis tends to cause changes in cellular microenvironmental factors. The variations of the microenvironment can serve as an indicator of the degree of apoptosis. Thus, the development of a smart and facile probe responding to cellular microenvironmental factors is significant for visualizing the apoptotic process. In this research, we designed a novel dual-color fluorescent probe, Lyso-DCPV, which incorporates N, N-diethyl coumarin as its polarity-responsive module, and the twisting double bond between N, N-diethyl coumarin and N-propyl quinoline as its viscosity-responsive module. The green fluorescence of Lyso-DCPV is sensitive to polarity changes, diminishing as polarity increases. Conversely, the red fluorescence intensifies with escalating viscosity. The probe specifically targets lysosomes, producing green fluorescence in live cells. Due to Lyso-DCPV’s acute sensitivity to changes in polarity and viscosity, it is well-suited to observe variations in the intracellular lysosomal microenvironment during drug-induced apoptosis. We also employed Lyso-DCPV for the dynamic assessment of polarity and viscosity during peroxide-induced apoptosis, enabling the observation of cell viability through variations in the probe’s emission color and intensity. The distinct probe will pave the way for novel strategies in evaluating apoptosis-related drugs. Moreover, Lyso-DCPV stands as an exemplary molecular instrument to elucidate the interplay between polarity and viscosity, facilitating the exploration of the interrelation in the cellular microenvironment during apoptosis.

Rhein induces apoptosis of AGS and MGC803 cells by regulating the Ras/PI3K/AKT and p38/MAPK signaling pathway.

Rhein is one of the main bioactive compounds in the Polygonaceae plant, and has been proven to have anti-cancer activity in some reports. But the mechanism of Rhein in the treatment of gastric cancer (GC) is limited reported. In this research, network pharmacology combined with in vitro experiments was used for systematically studying the mechanism of Rhein. Network pharmacology confirmed the major effect signaling pathway and key targets of Rhein in the treatment of GC. Cell viability assay, colony formation assay, fluorescence probe assay, apoptosis assay, western blot and qRT-PCR verified the mechanism of Rhein in the treatment of GC cells (AGS and MGC803 cells). The results showed that Rhein significantly induced the apoptosis process of AGS and MGC803 cells by regulating the Ras/phosphoinositide-3 kinase (PI3K)/protein kinase B (AKT) and the p38/mitogen-activated protein kinase signaling pathways. The AKT activator (SC79) and p38 inhibitor (SB202190) inhibited Rhein-induced apoptosis. All results proved that Rhein could be recognized as a potential natural drug for the treatment of GC.

The essential function of cathepsin X of the orange-spotted grouper, Epinephelus coioides during SGIV infection

Cathepsin X, a class of cysteine proteases in the lysosome, involved in intracellular protein degradation processes. Numerous reports revealed that many kinds of cysteine proteases played a crucial role in pathogen invasion. To investigate the relationship between cathepsin X of teleost fish and virus infection, EcCX was cloned and characterized in the orange-spotted grouper, Epinephelus coioides. The open reading frame (ORF) of EcCX included 909 nucleotides and encoded a protein consisting of 302 amino acids, which shared 75% and 56% identity with zebrafish and humans, respectively. The protein EcCX mainly consisted of a signal peptide (1–19 aa), a pro-pre-peptide region (20–55 aa), and a mature cysteine protease region (56–302 aa). Subcellular localization analysis showed that EcCX was mainly distributed in the cytoplasm, but EcCX ectoped to the vicinity of apoptotic vesicles in FHM cells during SGIV infection. Following stimulation with SGIV or Poly (dA:dT), there was a notable rise in the expression levels of EcCX. EcCX overexpression facilitated virus infection, upregulated the production of inflammatory factors, and induced the activation of the NF-κB promoter. Furthermore, the overexpression of EcCX also accelerated the process of SGIV-induced apoptosis, potentially by enhancing the promoter activity of P53 and AP-1. Overall, our findings demonstrated a correlation between the function of EcCX and SGIV infection, providing a new understanding of the mechanisms involved in fish virus infection.

Molecular Docking of Natural Alkaloids with Bcl-xL Protein in The Apoptosis Process

Background: The anti-apoptotic protein Bcl-xL is a viable target for cancer therapy due to its critical role in cancer formation and resistance to chemotherapy. Insights into Bcl-xL’s role have spurred the development of a new category of cancer drugs called Bcl-xL inhibitors, which mimic the BH3-only protein to cause apoptosis. It could be initiated using alkaloids, owing to their remarkable biological characteristics. Alkaloids, among the biggest obtainable from plants, possess a distinctive structure characterized by the presence of a nitrogen atom in various positions within the molecule. Objective: In the current study, the potential of various alkaloids as Bcl-xL inhibitors was investigated through a molecular docking study. Methods: AutoDock Vina software was used to perform docking simulations of the alkaloids. Results: Ten alkaloids/Bcl-xL protein complexes demonstrated strong binding affinities less than -8.0 kcal/mol-1. These complexes include phaenthine (26), 4,5-Dioxoaporphine (1), anonaine (2), atherospermidine (4), limacine (14), liriodenine (16), monomargine (18), ouregidione (24), oxostephanine (25), and taliscanine (29) as the ligand of Bcl-xL protein. Notably, the complexes of Bcl-xL/dicentrinone (10), ouregidione (24), stepharine (28), and taliscanine (29) displayed three to four hydrogen bonds along with hydrophobic contacts. Conclusion: These results suggest that certain alkaloids could act as potential Bcl-xL inhibitors, mimicking BH3-only proteins and thereby potentially triggering apoptosis during cancer treatment.