Number Of Apoptotic Cells Research Articles

P0031 The role of LAT1 in colitis and colitis-associated tumourigenesis

Abstract Background Inflammatory bowel disease (IBD) remains a public health challenge, with its incidence and prevalence increasing globally [1]. IBD is known to have an increasing risk of developing colitis-associated cancer (CAC) [2], and it is important to elucidate the pathophysiology of CAC to invent a counteraction to prevent it. L-type amino acid transporter 1 (LAT1) has been reported to be upregulated during the active phase of ulcerative colitis [3] and colorectal cancer (CRC) [4]. However, its role and mechanisms in the progression of colitis and CRC development from a chronic inflammatory background remain unclear. Methods To investigate the role of LAT1 in tumour development with a colitis background, mice with intestinal epithelium-specific deletions of LAT1 (LAT1fl/fl; vil-cre) were subjected to azoxymethane/ dextran sulfate sodium (AOM/DSS) CAC model. Organoids derived from these mice were also analysed. Results LAT1 was detected at the base of colonic crypts and upregulated in DSS-induced colitis. Deletion of LAT1 in intestinal epithelium led to more severe inflammatory injury and delayed tissue repair following DSS treatment. Crypts derived from LAT1fl/fl; vil-cre mice formed fewer colonic organoids than LAT1fl/fl crypts. Furthermore, LAT1 was also upregulated in AOM/DSS-induced tumour tissues. The expression of inflammatory cytokine genes was significantly increased in LAT1-deleted tumours; however, no overall difference in colon tumour number or size was observed between the two groups. Accordingly, cell proliferation and apoptotic cell number were similar between LAT1-deleted tumours and those with sufficient LAT1. Conclusion The results of this study showed that LAT1 deficiency exacerbated intestinal inflammatory injury and delayed tissue repair by impairing the maturity of colonic crypt cells. Contrary to the expectation, however, LAT1 deficiency did not phenotypically affect overall colonic tumour development in the AOM/DSS-induced model. It may be partly because of the severe chronic colitis and increased inflammatory status within the tumours due to LAT1 deficiency in LAT1fl/fl; vil-cre mice, which might have compensated for tumour growth advantage of sufficient amino acid supplementation in LAT1 expressing control mice. Our results offer insights into how nutrient intake, such as daily diet, may influence the progression of colitis, and provide insights into the potential of LAT1-targeted therapies for clinical CRC treatment.

Nicotine Ameliorates α-Synuclein Preformed Fibril-Induced Behavioral Deficits and Pathological Features in Mice.

Epidemiologic study suggests that nicotine reduces the risk of Parkinson's disease (PD) and thus could serve as a potential treatment. In this study, we aimed to investigate the effect of nicotine on the behavioral phenotypes and pathological characteristics of mice induced by human alpha-synuclein preformed fibers (α-syn-PFF). Mice were injected with 5µg of human α-syn-PFF in the hippocampus while administering nicotine-containing drinking water (200µg/mL). After 1month, the motor ability, mood, spatial learning, and memory ability of the PD phenotype-like model mice were detected using open field, rotarod, Y maze, and O maze tests. The expression of pathological α-syn and apoptotic proteins, as well as the number of glial and neural stem cells in the hippocampus of mice, was detected using western blot and immunofluorescence. The results demonstrated that nicotine significantly reduced pathological α-syn accumulation, α-syn serine 129 phosphorylation, and apoptosis induced by α-syn-PFF injection in the hippocampus of mice. Nicotine also inhibited the increase in the number of glia, microglia, and neuronal apoptotic cells, and it decreased the expression of PI3K and Akt while also exhibiting significant memory impairment, motor deficits, and anxiety-like behavior. In conclusion, our findings suggest that nicotine ameliorates behavioral deficits and pathological changes in mice by inhibiting human α-syn-PFF-induced neuroinflammation and apoptosis.

Increased apoptosis in late-developing in vitro fertilized bovine blastocysts decreases successful pregnancy.

Pregnancy in cattle after embryo transfer (ET) is influenced by several factors, including embryo quality. Therefore, preparing high-quality embryos with the greatest developmental potential is essential for achieving a successful pregnancy after ET. Meanwhile, blastocysts produced by in vitro fertilization (IVF) procedure have different developmental speed during in vitro culture (IVC) and they exhibited different competence in the establishment of pregnancy. This study aimed to identify the comparative features of early-, mid-, and late-developing bovine IVF blastocysts, when they first appeared at Day 7, 8, and 9 during IVC, respectively. In addition, the correlations between their molecular features and pregnancy ability were analyzed. The results showed no difference in the morphological characteristics, including total cell count and diameter, between the Day 7, 8, and 9 blastocysts. However, the pregnancy rate post-ET was significantly different between the groups at 51.7%, 36.7%, and 17.8% for Day 7, 8, and 9 blastocysts, respectively. During early embryo development, late-developing blastocysts demonstrated a reduced cell count in the inner cell mass and decreased expression of the early embryo developmental genes (Oct4 and Sox2) compared with the early- and mid-developing blastocysts. In addition, the number of apoptotic cells and apoptosis-related gene expression (increased Bax and decreased Bcl2) gradually elevated from the Day 7 to Day 9 blastocysts. However, there was no difference in mitochondrial activity and mitochondria-relevant gene expression (Tfam and Cox1) between the groups. Correlation analysis identified a significantly negative correlation between the pregnancy rate and the blastocysts' degree of apoptosis, indicating that the low pregnancy ability of late-developing blastocysts was mainly caused by increased apoptosis. This study's results may contribute to the field of animal biotechnology by assisting in establishing an improved strategy for bovine ET with IVF embryos.

Olfactory Impairment and Recovery in Zebrafish (Danio rerio) Following Cadmium Exposure.

Anthropic activities have significantly elevated cadmium levels, making it a significant stressor in aquatic ecosystems. Present in high concentrations across water bodies, cadmium is known to bioaccumulate and biomagnify throughout the food chain. While the toxic effects of cadmium on the organs and tissues of aquatic species are well-documented, little is known about its impact on sensory systems crucial for survival. Consequently, this study investigated the impact of short-term exposure (96 h) to 25 µM cadmium chloride on the olfactory system of adult zebrafish. The research aimed to assess structural and functional changes in the zebrafish's olfactory lamellae, providing a deeper understanding of how cadmium affects the sense of smell in this aquatic species. After exposure, cyto-anatomical alterations in the lamellae were analysed using light microscopy and immunocytochemistry. They revealed severe lamellar edema, epithelial thickening, and an increased number of apoptotic and crypt cells. Rodlet and goblet cells also increased by 3.5- and 2.5-fold, respectively, compared to control lamellae, and collagen density in the lamina propria increased 1.7-fold. Cadmium upregulated metallothioneins and increased the number of PCNA-positive cells. The olfactory function was assessed through a behavioural odour recognition test, followed by a recovery phase in which zebrafish exposed to cadmium were placed in clean water for six days. The exposed fish performed poorly, failing to reach food in five consecutive trials. However, lamellar damage was reduced after the recovery period, and their performance improved, becoming comparable to the control group. These results suggest that cadmium disrupts the sense of smell, and that recovery is possible after short-term exposure. This evidence sheds light on aspects of animal survival that are often overlooked when assessing environmental pollution.

Protective effect of quercetin loaded on bifunctional periodic mesoporous organosilica against damage induced by irradiation on the male reproductive system

Preserving fertility is important in men under radiation therapy because healthy cells are also affected by radiation. Supplementation with antioxidants is a controversial issue in this process. Designing a biocompatible delivery system containing hydrophobic antioxidants to release control may solve these disagreements. Herein, a bifunctional periodic mesoporous organosilica (PMO) was designed to load quercetin (Quer) and its application was studied on damaged cells induced by irradiation on the male reproductive system. Quercetin-loaded on PMO significantly improved the length and width of the testis after irradiation compared to the Quer, alone (p < 0.001 and p < 0.001, respectively). Sperm viability was significantly higher in the Quer-loaded on PMO than Quer, alone after irradiation (p < 0.001). Irradiation significantly decreased the sperm count (p = 0.01), however, Quer and Quer-loaded on PMO could not increase them to the normal ranges. Quer alone and loaded on PMO significantly reduced the sperm with abnormal morphology after irradiation (p < 0.001). Quer alone, and loaded on PMO significantly increased daily production of sperm after irradiation (p < 0.001). The number of apoptotic cells significantly increased after irradiation (p < 0.001). After irradiation, Quer loaded on PMO significantly decreased the apoptotic cells compared to the irradiated (p < 0.001) and Quer, alone groups (p < 0.001). The novel synthesized PMO containing Quer reduced the side effects of irradiation on the male reproductive system.Graphical

MicroRNA-204-5p Deficiency within the vmPFC Region Contributes to Neuroinflammation and Behavioral Disorders via the JAK2/STAT3 Signaling Pathway in Rats.

Major depressive disorder (MDD) is usually considered associate with immune inflammation and synaptic injury within specific brain regions. However, the molecular mechanisms underlying the neural deterioration resulting in depression remain unclear. Here, it is found that miR-204-5p is markedly downregulated in the ventromedial prefrontal cortex (vmPFC) in a chronic unpredictable mild stress (CUMS) induce rat model of depression. Knockdown of miR-204-5p in the vmPFC of normal rats results in depression and anxiety-like behaviors accompanied with the activation of microglia, elevated levels of pro-inflammatory cytokines, and increased numbers of neural apoptotic cells, effects which appear to be mediated by activation of the JAK2/STAT3 signaling pathway. Electrophysiological recordings further demonstrate that knockdown of miR-204-5p induces abnormal excitability of pyramidal neurons. In contrast, upregulation of miR-204-5p in the vmPFC of CUMS rats significantly causes inhibition of JAK2/STAT3 signaling pathway, improvements in neuronal impairments, and an abolition of the depression and anxiety-like behaviors. Moreover, pharmacological blocking of the JAK2/STAT3 signaling pathway significantly ameliorates abnormal behaviors resulting from miR-204-5p deficiency within the vmPFC. Collectively, these results provide robust evidence that the miR-204-5p/JAK2/STAT3 pathway may critically involve in the pathogenesis of depression, which may serve as potentially critical therapeutic target in the treatment of MDD.

Exploring the potential of gemcitabine-metal–organic frameworks in combating pancreatic cancer under ketogenic conditions

BackgroundInadequate treatment responses, chemotherapy resistance, significant heterogeneity, and lengthy treatment durations create an urgent need for new pancreatic cancer therapies. This study aims to investigate the effectiveness of gemcitabine-loaded nanoparticles enclosed in an organo-metallic framework under ketogenic conditions in inhibiting the growth of MIA-PaCa-2 cells.MethodsGemcitabine was encapsulated in Metal–organic frameworks (MOFs) and its morphology and size distribution were examined using transmission electron microscopy (TEM) and Dynamic light scattering (DLS) with further characterization including FTIR analysis. Various drug groups were established to evaluate their influences on cell cytotoxicity, apoptosis rate, cell cycle distribution, levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), and cell migration.ResultsThe gemcitabine-MOF was thoroughly analyzed to determine its size, morphology, and chemical composition, confirming its successful preparation. The treatment results showed an increase in the number of apoptotic cells following gemcitabine-MOF treatment, which was found to be associated with cell cycle arrest in the sub-G1 phase. Moreover, these treatments also resulted in reduced cell migration, decreased activity of antioxidant enzymes (SOD, GPx), and increased accumulation of MDA. Additionally, when exposed to ketogenic conditions (where beta-hydroxybutyrate is present in a glucose-limited medium), there was a further increase in cell cycle arrest, accompanied by a more pronounced decrease in SOD and GPx activity, as well as decreased migration.ConclusionThe use of metal–organic framework to encapsulate gemcitabine yielded notable pro-apoptotic effects in MIA-PaCa-2 cells with which ketogenic conditions had a synergistic effect that can hold promise for improving therapeutic options.Graphical

The Proapoptotic Effect of MB-653 Is Associated with the Modulation of Metastasis and Invasiveness-Related Signalling Pathways in Human Colorectal Cancer Cells.

Colorectal cancer is one of the most common cancers worldwide and has a high mortality rate. In this study, we investigated the cytotoxic, proapoptotic, and anti-invasive effects of the synthetic indole phytoalexin MB-653. The antiproliferative effect was determined using an MTT assay, showing IC50 values of 5.8 ± 0.3 μmol/L for HCT116 cells and 6.1 ± 2.1 μmol/L for Caco2 cells. Flow cytometry and Western blot analysis were employed to investigate the molecular mechanisms underlying cytotoxicity, proapoptotic action, and anti-invasion effects. The proapoptotic activity was evidenced by the activation of caspases 3 and 7, mitochondrial dysfunction, and an increased number of apoptotic cells, confirmed by annexin V/PI and AO/PI staining. Additionally, MB-653 induces dose-dependent G2/M phase cell cycle arrest, the cause of which could be cyclin B1/CDC2 complex dysfunction and/or a decrease in α-tubulin protein expression. Another important observation was that MB-653 modulated several signalling pathways associated with various cellular activities, including survival, proliferation, tumour invasiveness, metastasis, and epithelial-mesenchymal transition (EMT). We further demonstrated its safety for topical and parenteral application. To sum up, our results indicate the real potential of MB-653 in treating colorectal cancer.

Effect of bromelain on ischemia-reperfusion injury in the torsion model created in polycystic and normal ovarian tissues.

Due to its increased volume, polycystic ovarian tissue is more prone to torsion than normal ovarian tissue. In treating ovarian torsion, detorsion is applied to ensure oxygenation of hypoxic tissues. However, the resulting oxygen radicals cause tissue damage. Bromelain is a substance obtained from pineapple, and studies in the literature show it is used as an antioxidant. This study aimed to evaluate the damage caused by ischemia-reperfusion (I/R) in the torsion-detorsion model created in normal and polycystic ovarian tissue and investigate the role of bromelain in this damage. Polycystic ovarian tissue was created by applying dihydroepiandrosterone sulfate to rats. Afterward, a torsion-detorsion model was used for all rats. The rats were divided into six groups: the polycystic ovary sham-operated group (P-S), the normal ovary sham-operated group (N-S), the polycystic ovary ischemia/reperfusion group (P-IR), the normal ovary ischemia/reperfusion group (N-IR), the polycystic ovary ischemia/reperfusion group treated with bromelain (P-IRB), and the normal ovary ischemia/reperfusion group treated with bromelain (N-IRB). After the procedure, tissues were collected for histopathological examination, and MDA, TUNEL, and NF-κB levels were measured. This study detected significant decreases in MDA and NF-κB levels and apoptotic cell numbers assessed by TUNEL staining in groups with IR damage and given bromelain compared to the control groups. The number of TUNEL-positive cells was found to be highest in the P-IR group (8.80 ± 2.98) and significantly lower in the bromelain-administered P-IRB (1.04 ± 1.09) and N-IRB (0.52 ± 0.58) groups (p< 0.05). NF-κB expression was also high in P-IR and N-IR groups, while it was significantly decreased in bromelain-treated groups (P-IRB and N-IRB) (p< 0.05). In addition, IR damage was more pronounced in polycystic ovary tissue than in normal ovary tissue. Ischemia perfusion damage may be more pronounced in polycystic ovarian tissue than in normal ovarian tissue. Bromelain may be preferred to prevent I/R injury caused by ovarian torsion. It is also thought that bromelain may function in treating polycystic ovaries, and further studies can be conducted on this subject.

Stem Cell-Derived Exosomes as a Therapeutic Option for Spinal Cord Injuries; a Systematic Review and Meta-Analysis.

Exosomes function as cell signaling carriers and have drawn much attention to the cell-free treatments of regenerative medicine. This meta-analysis aimed to investigate the efficacy of mesenchymal stem cell-derived (MSC-derived) exosomes in animal models of spinal cord injuries (SCI). A comprehensive search was conducted in Medline, Embase, Scopus, and Web of Science to attain related articles published by January 31, 2023. The eligible keywords were correlated with the spinal cord injury and MSC-derived exosomes. The evaluated outcomes were locomotion, cavity size, cell apoptosis, inflammation, neuro-regeneration, and microglia activation. A standardized mean difference was calculated for each sample and a pooled effect size was reported. 65 papers fully met the inclusion criteria. Treatment with MSC-derived exosomes ultimately improved locomotion and shrunk cavity size (p<0.0001). The administration of MSC-derived exosomes enhanced the expression of beta-tubulin III, NF200, and GAP-43, and increased the number of NeuN-positive and Nissl-positive cells, while reducing the expression of glial fibrillary acidic protein (p<0.0001). The number of apoptotic cells in the treatment group decreased significantly (p<0.0001). Regarding the markers of microglia activation, MSC-derived exosomes increased the number of CD206- and CD68-positive cells (p=0.032 and p<0.0001, respectively). Additionally, MSC-derived exosome administration significantly increased the expression of the anti-inflammatory interleukin (IL)-10 and IL-4 (p<0.001 and p=0.001, respectively) and decreased the expression of the inflammatory IL-1b, IL-6, and TNF-a (p<0.0001). MSC-derived exosome treatment resulted in a significantly improved locomotion of SCI animals through ameliorating neuroinflammation, reducing apoptosis, and inducing neuronal regrowth by facilitating a desirable microenvironment.

Echinacoside alleviates Ang II-induced cardiac fibrosis by enhancing the SIRT1/IL-11 pathway.

Echinacoside (ECH) is an anti-fibrotic phenylethanoid glycoside derived from the Cistanche plant that protects against cardiac dysfunction by mitigating apoptosis, oxidative stress, and fibrosis. Nevertheless, ECH's precise function and mechanisms in addressing cardiac fibrosis are still not fully understood. In our current investigation, we induced cardiac fibrosis in mice by administering Angiotensin II (Ang II) and subsequently assessed the effects of ECH treatment four weeks post-fibrosis induction. Additionally, in an in vitro setting, we exposed cardiac fibroblasts (CFs) to Ang II to prove the anti-fibrotic mechanisms of ECH. ECH treatment effectively reversed cardiac fibrosis in the mice model. ECH treatment significantly reduced the levels of fibrosis-related genes, such as α-SMA, Collagen I, and Collagen III (all, P<0.001). Moreover, it reduced the number of apoptotic cells and regulated the expression of apoptosis-related genes, such as BAX and BCL-2 (all, P<0.001). ECH treatment also positively affected serum levels of markers associated with cardiac fibrosis, including LDH, CK-MB, ANP, BNP, CTnl, and CTnT (all, P<0.001), in the in vivo experiments. In the in vitro studies, ECH pretreatment alleviated cardiac fibroblast apoptosis and reduced cell migration, collagen deposition, and MMP expression (all, P<0.001). In our in vivo and in vitro investigations, we observed that ECH treatment reversed the down-regulation of SIRT1 and up-regulation of IL-11 following cardiac fibrosis. The results suggest that the protective effects of ECH may involve regulating the SIRT1/IL-11 pathway. ECH may protect against Ang II-induced cardiac fibrosis via the SIRT1/IL-11 pathway.

The effect of KUS121, a novel VCP modulator, against ischemic injury in random pattern flaps.

Surgery using skin flaps is essential for soft tissue reconstruction. However, postoperative ischemic injury of the skin flap is a major complication and a top concern after the surgery. Currently, evidence-based drugs to fully prevent ischemic injury are not available. The purpose of this study was to evaluate the effect of KUS121, a VCP modulator, on flap ischemia using a rodent model. 26 Sprague-Dawley rats were randomly divided into two groups. The experimental group was intraperitoneally administered with 100 mg/kg KUS121 dissolved in 5% glucose solution 1 hour before surgery and once per day after surgery. The control group received the same amount of glucose solution on the same schedule. On day 7, 33.6 ± 3.7% of skin flaps in the control group had developed black necrosis compared with 26.4 ± 3.6% in the KUS121 group (p < 0.01). Immunohistochemistry showed that the KUS121 treatment reduced the number of apoptotic cells in the distal third of the flap (p < 0.01); moreover, in the KUS121-treated rats, the number of cells expressing CHOP, an endoplasmic reticulum (ER) stress marker, in the middle third of the flap was significantly lower than in the controls (p < 0.01). We examined the mRNA expression of Ddit3 (CHOP) and Casp3 (caspase-3) on day one after the surgery; mRNA expression of both genes appeared to decrease in the KUS121 group, as compared with the control group, although differences between groups were not significant. Thus, in a random pattern flap, KUS121 reduces ER stress and the number of apoptotic cells, thereby reducing ischemic damage of the flap.

Kif15 regulates Coro1a+ cell migration and phagocytosis in zebrafish after spinal cord injury.

The role of immune cells is crucial in nerve regeneration following spinal cord injury. Kif15, a member of the kinesin family, has been shown to enhance macrophage phagocytosis. This study investigates the impact of Kif15 deficiency on immune cells in zebrafish with spinal cord injury. Using kif15 morphants in Tg(coro1a:EGFP) zebrafish, we observed increased recruitment of Coro1a+ cells to the injury site, followed by a rapid decline in kif15 morphants. Transcriptome analysis revealed that inflammatory and phagocytic signals were significantly enhanced at 1-hour post-injury (hpi), while MAPK pathways indicated growth at 24 hpi. Enhanced phagocytosis was confirmed using neutral red particles, and the Kif15 inhibitor GW406108X further supported increased migration and phagocytosis in macrophages. Activation of Cdc42 and RhoA was significantly increased, contributing to cell motility and phagocytosis. Additionally, the number of apoptotic cells was reduced in kif15 morphants, suggesting that Kif15 depletion could activate immune cells and efficiently remove apoptotic cells. Our study provides in vivo evidence that Kif15 is involved in immune cell migration and phagocytosis and suggests potential therapeutic roles for Kif15 inhibitors in spinal cord injury treatment.

Deptor protects against myocardial ischemia-reperfusion injury by regulating the mTOR signaling and autophagy

Deptor knockout mice were constructed by crossing Deptor Floxp3 mice with myh6 Cre mice, establishing a myocardial ischemia-reperfusion (I/R) model. Deptor knockout mice exhibited significantly increased myocardial infarction size and increased myocardial apoptosis in vivo. ELISA analysis indicated that the expression of CK-MB, LDH, and CtnT/I was significantly higher in the Deptor knockout mice. Deptor siRNA significantly reduced cell activity and increased myocardial apoptosis after I/R-induced in vitro. Deptor siRNA also significantly up-regulated the expression of p-mTOR, p-4EBP1, and p62, and down-regulated the expression of LC3 after I/R induction. Immunofluorescence indicated that LC3 dual fluorescence was weakened by Deptor knockout, and was enhanced after transfection with Deptor-overexpression plasmids. Treatment with OSI027, a co-inhibitor of mTORC1 and mTORC2, in either Deptor knockout mice or Deptor knockout H9C2 cells, resulted in a significant reduction in infarction size and apoptotic cardiomyocytes. ELISA analysis also showed that the expression of CK-MB, LDH, and CtnT/I were significantly down-regulated by treatment with OSI027. CCK-8 cell viability indicated that cell viability was enhanced, and the number of apoptotic cells was decreased in vitro following treatment with OSI027. These results revealed that OSI027 exerts a protective effect on myocardial ischemia/reperfusion injury in both an in vivo and in an in vitro model of I/R. These findings demonstrate that Deptor protects against I/R-induced myocardial injury by inhibiting the mTOR pathway and by increasing autophagy.

Nerelimomab Alleviates Capsaicin-Induced Acute Lung Injury by Inhibiting TNF Signaling and Apoptosis.

Background: Capsaicin is commonly used as a flavoring and a riot control agent. However, long-term exposure or high doses can cause acute lung injury in military and police personnel. The mechanisms underlying capsaicin-induced pulmonary toxicity remain unclear. Therefore, this study investigated the molecular mechanisms involved in capsaicin-induced acute lung injury using C57BL/6N mice. Methods: Through both transcriptomic and proteomic analyses of mouse lung tissue, we identified the involvement of the TNF signaling pathway in capsaicin-mediated acute lung injury. Next, we explored the role of TNF signaling in the progression of acute lung injury to identify potential therapeutic targets. In a capsaicin-induced acute lung injury mouse model and A549 cells, we assessed the therapeutic potential of the TNF-α antibody Nerelimomab. Compared with the control group, TNF-α up-regulation was observed, which correlated with increased pathological changes and elevated IL-6 (p < 0.01) and IL-18 (p < 0.01) levels, both in vivo and in vitro. Results: Flow cytometry revealed that compared to the capsaicin group, Nerelimomab treatment reduced the number of capsaicin-induced apoptotic cells (p < 0.001) and was associated with an increased Bcl-2/Bax ratio (p < 0.01) and reduced cleaved caspase 3 expression (p < 0.001). Analysis of A549 cells treated with capsaicin and Nerelimomab corroborated these results. These findings confirm the involvement of the TNF signaling pathway in capsaicin-induced acute lung injury and the apoptosis of alveolar epithelial cells. Conclusions: In conclusion, capsaicin inhalation can cause acute lung injury, and targeting the TNF signaling pathway offers a promising therapeutic strategy. Nerelimomab demonstrates significant potential in alleviating acute lung injury by inhibiting inflammatory mediator release and diminishing apoptosis. Based on transcriptomic and proteomic analyses, this study highlights the crucial role of the TNF signaling pathway in capsaicin-induced acute lung injury and supports the therapeutic efficacy of Nerelimomab in reducing epithelial apoptosis.

The niosomal nelarabine as a promising nano combination for retinoblastoma treatment: an in vitro study—experimental research

Introduction: Retinoblastoma (RB), the most commonly occurring intraocular malignancy among children globally, represents 3% of childhood cancers. In the current study, the authors aim to evaluate the effectiveness of a new formulation of nelarabine (niosomal nelarabine) on RB cancer cells. Methods: Field emission scanning electron microscopy (FE-SEM) and dynamic light scattering (DLS) characterized the physical properties of nelarabine nanoparticles. After cultivation of the Y79 cell line, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was performed to determine IC50 of niosomal nelarabine (Nio-Nelarobine) and also the cytotoxicity of Nio-Nelarobine and doxorubicin against Y79 cell line was investigated. The level of apoptosis was assessed by flow cytometry in selected groups. Also, the PTEN/AKT/FOXO1 gene expression level was measured using qRT-PCR. Results: Y79 cell lines were treated with Nio-Nelarobine and doxorubicin. The treatment resulted in a dose-dependent inhibition of Y79 cell viability. However, Nio-Nelarobine showed a higher inhibitory activity with a diameter of about 167 nm. Both Nio-Nelarobine and doxorubicin induced apoptosis in cells, but Nio-Nelarobine treatment resulted in a higher number of apoptotic cells than doxorubicin treatment. The qRT-PCR results showed that the treatment with Nio-Nelarobine and doxorubicin led to an increase in the expression of PTEN and FOXO1 genes, while decreasing the expression of the AKT gene. Furthermore, the statistical significance of these results was higher in the Nio-Nelarobine group than in the doxorubicin group. Conclusions: Nio-Nelarobine may be a functional therapeutic combination for RB treatment. Further experimental and preclinical investigations are necessary to verify this impact in greater detail.

Efficacy and Safety of Natural Apigenin Treatment for Alzheimer's Disease: Focus on In vivo Research Advancements.

Alzheimer's Disease (AD) is the most common dementia in clinics. Despite decades of progress in the study of the pathogenesis of AD, clinical treatment strategies for AD remain lacking. Apigenin, a natural flavonoid compound, is present in a variety of food and Chinese herbs and has been proposed to have a wide range of therapeutic effects on dementia. To clarify the relevant pharmacological mechanism and therapeutic effect of apigenin on animal models of AD. Computer-based searches of the PubMed, Cochrane Library, Embase, and Web of Science databases were used to identify preclinical literature on the use of apigenin for treating AD. All databases were searched from their respective inception dates until June 2023. The meta-analysis was performed with Review manager 5.4.1 and STATA 17.0. Thirteen studies were eventually enrolled, which included 736 animals in total. Meta-analysis showed that apigenin had a positive effect on AD. Compared to controls, apigenin treatment reduced escape latency, increased the percentage of time spent in the target quadrant and the number of plateaus traversed; apigenin was effective in reducing nuclear factor kappa-B (NF-κB) p65 levels; apigenin effectively increased antioxidant molecules SOD and GSH-px and decreased oxidative index MDA; for ERK/CREB/BDNF pathway, apigenin effectively increased BDNF and pCREB molecules; additionally, apigenin effectively decreased caspase3 levels and the number of apoptotic cells in the hippocampus. The results show some efficacy of apigenin in the treatment of AD models. However, further clinical studies are needed to confirm the clinical efficacy of apigenin.

Effects of salinity stress on the growth performance, histological characteristics, and expression of genes related to apoptosis and immunity in channel catfish (Ictalurus punctatus).

Salinity is an important environmental factor affecting fish growth and development. To investigate the effects of salinity stress on the growth performance, tissue structures, and expression of genes related to apoptosis and immune response in large-sized channel catfish (Ictalurus punctatus) juveniles, an 8-week salinity stress experiment was conducted. Six salinity levels (3, 3.8, 4.7, 5.9, 7.3, and 9 psu) were set according to an equal logarithmic concentration gradient method, along with a control group (0), and growth performance and physicochemical indices were measured. The survival rate of channel catfish in all salinity groups was 100%. Body length, body weight, weight gain rate, and specific growth rate decreased with increasing salinity, with higher salinity levels resulting in more significant reductions in growth performance. At 9 psu, both the specific growth rate (SGR) and weight gain rate (WGR) decreased significantly to 0.61%/day and 40.86%, respectively (p < 0.05). Histological analysis results indicated that with the increase in salinity, the number of intestinal mucosal folds relatively increased, while the number of goblet cells gradually decreased. Hepatocytes became more densely packed, and the hepatic lobule gaps widened. Apoptosis detection results revealed that in the liver, the number of apoptotic cells at 4.7 psu salinity was more than that in the control group and at 9 psu salinity. In the intestine, the number of apoptotic cells at 9 psu salinity was significantly higher than in the other two groups (p < 0.05). Quantitative polymerase chain reaction (qPCR) analysis of the expression patterns of genes related to apoptosis and immunity showed that the expression levels of caspase 3, caspase 8, INF-I, IL-1β, and bax genes in the liver and intestinal tissues were higher in the experimental groups than in the control group, while the expression of bcl-2 decreased with increasing salinity in liver tissue but increased in intestinal tissue. These findings can provide theoretical guidance for the aquaculture of channel catfish in saline-alkali land.

Protective effect of Huanglian Pingwei San on DSS-induced ulcerative colitis in mice through amelioration of the inflammatory response and oxidative stress.

Ulcerative colitis (UC) results in the breakdown of the mucosal barrier caused by persistent inflammation and oxidative stress. Huanglian Pingwei San (HLPWS) is a commonly prescribed traditional Chinese medicine for treating colitis, but the precise mechanism remains unclear. The aim of this study was to systematically investigate the protective effect of HLPWS on UC mice and to elucidate the underlying mechanisms involved. UC mouse model was established in C57BL/6 mice via 2.25% dextran sulfate sodium (DSS). The chemical composition of HLPWS was examined through UPLC/MS Q-TOF analysis. The efficacy of HLPWS in treating UC was assessed. A TUNEL assay was used to detect apoptotic cells. An ELISA was used to evaluate the levels of inflammatory cytokines in colon tissues and serum. The percentages of Treg and Th17 cells were measured via flow cytometry. The protein expression in the colonic tissue was validated via immunohistochemistry (IHC) and Western blotting. HLPWS significantly improved UC symptoms and colon tissue histology in mice. The structure and function of the intestinal barrier were restored by HLPWS treatment, as shown by increased DAO content, reduced levels of FITC-dextran, and increased protein expression of ZO-1, occludin, claudin, and MUC2. HLPWS dose-dependently decreased the number of apoptotic cells by inhibiting P53, P21, P27, cleaved caspase 3, and p-H2AX expression. HLPWS also reduced abnormal oxidative stress by reducing Keap1 expression and increasing Nrf2 and HO-1 levels. Furthermore, HLPWS rebalanced the Treg/Th17 ratio to alleviated inflammatory reactions in UC mice. These findings suggest that HLPWS alleviated colonic intestinal barrier dysfunction in UC mice by reducing oxidative stress and restoring immune balance. This study underscores the potential therapeutic benefits of HLPWS and highlights its potential as a future pharmaceutical candidate for UC treatment.

Molecular Dynamics and Spatial Response of Proliferation and Apoptosis in Wound Healing and Early Intestinal Regeneration of sea cucumber Apostichopus japonicus

The sea cucumber, Apostichopus japonicus, exhibits significant regenerative capabilities. To ensure survival and reduce metabolic costs under adverse conditions, A. japonicus can expel intestine, respiratory trees and other internal organs. It takes only 14 days to regenerate a fully connected, lumen-containing intestine. Despite numerous reports characterizing the cellular events in intestinal regeneration, limited investigation has been conducted on the molecular events that occur during wound healing and the initial stages of regeneration after evisceration. Here, we identified differentially expressed genes (DEGs) during wound healing (6 hours post-evisceration, Aj6hpe) and early intestinal regeneration (Aj1dpe, Aj3dpe, Aj7dpe). Cell proliferation and apoptosis were detected by EdU and TUNEL assays, respectively. Results demonstrated that calcium ion and neuroactive ligand-receptor interaction were involved in the transmission of injury signals from evisceration to Aj1dpe. The main events occurring in the wound healing and early regeneration process were autophagy, apoptosis, dedifferentiation, migration and shutdown of feeding. Cell proliferation was primarily observed during the lumen formation stage. Maximal number of apoptotic cells were found during wound healing stage (6 hpe - 1 dpe). Consequently, the immune response is mainly mobilized by neural regulation after evisceration. Our findings bridge the gap between evisceration and regeneration, illuminating the molecular events that mediate damage response and initiate regeneration. This study significantly advances our understanding of the mechanisms underlying intestinal regeneration.