Search

Background: Metformin (Met) has been reported to play the key role in the pathogenesis of polycystic ovary syndrome (PCOS). However, the precise mechanisms underlying the actions of Met in PCOS remain incompletely understood. This study aimed to confirm the mechanism of Met interacting with a long non‐coding RNA LINC00548 in PCOS. Methods: Ovarian granulosa cells (OGCs) were incubated 500 nM dihydrotestosterone (DHT) to construct PCOS in vitro model and then were treated 20 μM Met. A series of cell experiments including Cell Counting Kit‐8, Terminal uridine nucleotide end labeling, and flow cytometry were performed to confirm the changes of OGC survival ability. Quantitative real‐time polymerase chain reaction was conducted to determine the levels of LINC00548, whereas Western blotting was applied to determine the levels of androgen receptor (AR) and klotho. Results: Met improved the cell viability and suppressed cell apoptosis in DHT‐treated OGCs. LINC00548 downregulated in DHT‐treated OGCs was upregulated by Met, and its overexpression further enhanced the positive effects of Met on the survival ability of DHT‐treated OGCs. In addition, Met could induce the upregulation of LINC00548 to suppress the activation of AR/klotho pathway in DHT‐treated OGCs. Conclusion: Overall, this study discovers that Met enhances the survival ability of OGCs in PCOS by elevating LINC00548 expression to suppress AR/klotho pathway. [ABSTRACT FROM AUTHOR]

Background: The significance of CXCL5 in pancreatic cancer is unclear, although it has been implicated in the malignant process of many different types of cancer. Research on the impact of CXCL5 on immune cell infiltration and the malignant phenotype of pancreatic cancer is needed. This study aimed to examine the connection between CXCL5 expression and immune cell infiltration and the malignant phenotype of pancreatic cancer. Methods: Tissue samples and clinical information were collected from 90 patients with pancreatic cancer. Tumour tissues and adjacent tissues were made into a tissue microarray and stained for immunohistochemistry analysis. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were performed to measure the expression level of CXCL5. CXCL5-overexpressing/CXCL5-knockdown cell lines were constructed via transfection for cytological experiments. CCK-8, cell apoptosis, cell cycle, cell invasion, and cell colony formation assays were used to detect the effect of CXCL5 on the malignant phenotype of pancreatic cancer cells. Finally, a mouse model of pancreatic cancer was constructed for in vivo verification. Results: Compared with control cells, pancreatic cancer cells overexpressing CXCL5 exhibited increased proliferation, migration, and invasion but decreased apoptosis. Conversely, knockdown of CXCL5 did not enhance the malignant phenotype of pancreatic cancer cells. Spearman correlation analysis indicated that there was a significant negative correlation between CXCL5 levels and the CD8 IRS. However, there was a significant positive correlation between FOXP3 IRS and CXCL5 levels. Conclusions: CXCL5 is highly expressed in pancreatic cancer and promotes the malignant phenotype of pancreatic cancer cells. CXCL5 is associated with immunosuppressive FOXP3 + T-cell infiltration, which facilitates the formation of an immunosuppressive microenvironment (with low CD8 + T-cell infiltration). [ABSTRACT FROM AUTHOR]

Rehmannia glutinosa is widely recognized as a prominent medicinal herb employed by practitioners across various generations for the purpose of fortifying kidney yin. Within Rehmannia glutinosa, the compound known as catalpol (CAT) holds significant importance as a bioactive constituent. However, the protective effects of CAT on kidneys, including ameliorative effects on chronic kidney disease — most prominently renal anemia and renal fibrosis — have not been clearly defined. In this study, the kidney injury model of NRK-52E cells and C57BL/6N male mice was prepared by exposure to aristolochic acid I (AA-I), and it was discovered that CAT could ameliorate oxidative stress injury, inflammatory injury, apoptosis, renal anemia, renal fibrosis, and other renal injuries both in vivo and in vitro. Further treatment of NRK-52E cells with Nrf2 inhibitors (ML385) and activators (ML334), as well as NF-κB inhibitors (PDTC), validated CAT's ability to target Nrf2 activation. Furthermore, the expression of phosphorylated NF-κB p65, IL-6, and Cleaved-Caspase3 protein was inhibited. CAT also inhibited NF-κB, and then inhibited the expression of IL-6, p-STAS3, TGF-β1 protein. Therefore, CAT can regulate Nrf2/NF-κB signaling pathway, significantly correct renal anemia and renal fibrosis, and is conducive to the preservation of renal structure and function, thus achieving a protective effect on the kidneys. [ABSTRACT FROM AUTHOR]

Background and objective Isoliquiritigenin (ISL) is an important pharmacological constituent of Glycyrrhiza glabra, which possesses a range of physiological and pharmacological activities, as well as significant antitumor activity, and can be used as a potential drug for targeted cancer therapy. LINC01503 is an oncogene, which has been closely associated with the malignant biological processes of many cancers. The aim of this study was to investigate the effects of ISL on the proliferation, apoptosis, invasion and migration of lung squamous carcinoma cells by regulating LINC01503. Methods Plasma was collected from lung squamous carcinoma patients and healthy individuals treated at Tangshan People's Hospital from January 2021 to December 2022. The expression of LINC01503 in lung squamous carcinoma plasma, tissues and cells was detected by real-time quantitative fluorescence polymerase chain reaction (qRT-PCR). Lung squamous carcinoma cells were treated with different concentrations of ISL for 24 h, and LINC01503 expression was detected by qRT-PCR. The cells were treated in groups: si-NC group, si-LINC01503 group, DMSO (0.1% dimethyl sulfone) group, ISL group, pc DNA3.1(+)-NC group, pc DNA3.1(+)-LINC01503 group, ISL+pc DNA3.1(+)-NC group and ISL+pc DNA3.1(+)- LINC01503 groups. CCK-8 assay, clone formation assay, flow cytometry, Transwell assay and scratch assay were used to explore the effect of LINC01503 on the functional phenotype of lung squamous carcinoma cells. Results Fluorescence in situ hybridization results showed that the average fluorescence intensity of LINC01503 in tissue microarrays of lung squamous carcinoma patients was higher than that in paracancerous tissues (P<0.05). The expression of LINC01503 in the plasma of patients with lung squamous carcinoma was higher than that in the plasma of healthy individuals (P<0.05). Knockdown of LINC01503 inhibited the proliferation, invasion and migration of lung squamous carcinoma cells and promoted apoptosis (P<0.05). ISL inhibited the proliferation, invasion, migration and promoted apoptosis of lung squamous carcinoma cells (P<0.05). Overexpression of LINC01503 followed by intervention with ISL reversed the promotional effect of overexpression of LINC01503 on the proliferation, invasion and migration of lung squamous carcinoma cells as well as the inhibitory effect on apoptosis (P<0.05). Conclusion LINC01503 was highly expressed in lung squamous carcinoma, and LINC01503 could promote the proliferation, invasion and migration of lung squamous carcinoma cells and inhibit the apoptosis, ISL could inhibit the proliferation, invasion and migration of lung squamous carcinoma cells and promote apoptosis of lung squamous carcinoma cells by regulating the expression of LINC01503. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to establish a diagnostic model of endometriosis (EM) based on disulfidptosis‐related genes (DRGs). Materials and Methods: The mRNA expression data of EM were downloaded from the gene expression omnibus database and subjected to differential analysis, and co‐expression analysis was performed based on 10 disulfidptosis genes to acquire DRGs. The differentially expressed DRGs were subjected to biofunctional analysis. Lasso analysis and support vector machine‐recursive feature elimination (SVM‐RFE) analysis were employed to extract the intersection of feature genes as biomarkers, and the diagnostic values of biomarkers for EM were evaluated based on receiver operating characteristic curves. The correlations between biomarkers and the immune microenvironment were assessed by Pearson analysis of biomarkers and immune cell infiltration levels. Results: Transforming growth factor β stimulated protein clone 22 domain family member 4 (TSC22D4), and F‐box/SPRY domain‐containing protein 1 (FBXO45) worked as the diagnostic classifiers in EM, with an obvious decrease in FBXO45 expression and an evident increase in TSC22D4 expression. The areas under the curves of FBXO45 and TSC22D4 were 0.752 and 0.706, respectively, and the area of FBXO45 combined with TSC22D4 reached 0.865, suggesting that TSC22D4 and FBXO45 had high predictive values. The diagnostic markers were closely correlated with immune cell infiltration. Conclusion: The diagnostic markers constructed based on disulfidptosis are good predictors for EM, which have close correlations with EM. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether galangin (Gal) affects the proliferation, migration, invasion and apoptosis of osteosarcoma MG63 cells by regulating the cGAS/STING signaling pathway. Methods: Human osteosarcoma MG63 cells were cultured in vitro and treated with Gal at concentrations of 0, 5, 15, 25, 50, 100 and 200 μmol/L for 48 hours, and the effect of Gal on cell viability was detected by CCK-8 method. MG63 cells were divided into the control group (untreated cells), the Gal low concentration group (Gal-L group, treated with 50 μmol/L Gal), the Gal high concentration group (Gal-H group, treated with 100 μmol/L Gal), and the Gal-H+STING inhibitor group (Gal-H+H-151 group, treated with 100 μmol/L Gal+8 μmol/L H-151). EdU staining method, scratch healing test, Transwell chamber method and flow cytometry were used to detect cell proliferation, migration, invasion and apoptosis of cells in each group. Western blot was applied to detect the expression levels of cGAS and STING proteins in cells of each group. Results: Compared with the control group, the proliferation activity, migration, and invasion abilities of the cells in the Gal-L and Gal-H groups were significantly decreased (all P<0.05); the apoptosis rate and the expression levels of cGAS and STING proteins were significantly increased (all P<0.05). Compared with the Gal-H group, the proliferation activity, migration, and invasion abilities of the cells in the Gal-H+H-151 group were significantly increased (all P<0.05); the apoptosis rate and the expression levels of cGAS and STING proteins were significantly decreased (all P<0.05). Conclusion: Gal may inhibit the proliferation, migration and invasion and promote the apoptosis of osteosarcoma cells by activating the cGAS/STING signaling pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: Spodoptera litura is one of the most harmful lepidoptera pests in China, and is difficult to control due to its strong resistance to the current frequently used insecticide species. The requirement to develop pesticides with novel toxicology mechanisms to control S. litura is urgent. The quassinoid of bruceine D display outstanding systemic properties and strong insecticidal activity against S. litura, which possess notable application potential for integrative management of S. litura, but the mechanism of toxicity remains unclear. RESULTS: In this study, we found that bruceine D exerts potent growth inhibitory activity against S. litura, disrupting the ecdysone and juvenile hormone titers, and causing long‐term adverse effects. Association analysis between transcriptomics and metabolomics suggested that bruceine D affected the digestion and absorption capacity of S. litura larvae by inducing a strong oxidative stress response and cell apoptosis in the intestine. Further analysis demonstrated that bruceine D can inhibit the activities of digestive and antioxidant enzymes and induce malondialdehyde (MDA) and reactive oxygen species (ROS) overaccumulation in the midgut. Moreover, the protein level of Bax, cleavage caspase 3, and cytochrome c expressed in cytoplasm (cyto) were up‐regulated by bruceine D, while Bcl‐2 and cytochrome c expressed in mitochondria (mito) were down‐regulated. In addition, there was a noticeable increase in caspase‐3 protease activity. Histopathological observations revealed that bruceine D damages the structure of midgut epithelial cells and activates lysosomes, which subsequently disrupts the midgut tissue. CONCLUSION: Overall, our findings suggested that bruceine D induced excessive ROS accumulation in midgut epithelial cells. The resulting cell apoptosis disrupted midgut tissue, leading ultimately to reduced nutrient digestion and absorption in the midgut and the inhibition of larval growth. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The functional tea CFT-1 has been introduced into China as a nutraceutical beverage according to the "Healthy China" national project. The effects on human hepatocellular carcinoma (HCC) cells remain unclear and were investigated with the functional tea extract (purity > 98%). The morphological changes in the cells were observed with microscopes. Cell proliferation, migration, cycle distribution, and apoptotic effects were assessed by MTT, Transwell assays, and flow cytometry, respectively, while telomerase inhibition was evaluated with telomerase PCR ELISA assay kits. The CFT-1 treatment resulted in cell shrinkage, nuclear pyknosis, and chromatin condensation. CFT-1 suppressed the growth of Hep3B cells with IC50 of 143 μg/mL by inducing apoptosis and G0/G1 arrest in Hep3B cells. As for the molecular mechanism, CFT-1 treatment can effectively reduce the telomerase activity. The functional tea extract inhibits cell growth in human HCC by inducing apoptosis and G0/G1 arrest, possibly through a reduction in telomerase activity. These results indicate that CFT-1 extract exhibited in vitro anticancer activities and provided insights into the future development and utilization of CFT-1 as functional foods to inhibit the proliferation of HCC cells. [ABSTRACT FROM AUTHOR]

Objective: Elsholtzia, as a folk medicine, has been widely used in Miao, Yi, and Lahu nationalities and Tibetan and Chinese medicines in China. We aimed to elucidate the possible mechanisms of action of flavonoids of Elsholtzia densa Benth. (FIE) on apoptosis in HeLa human cervical cancer cells in vitro. Methods: Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) were used to detect the chemical constituents responsible for the effects of FIE. Network pharmacology was employed to predict the active constituents and their targets to explore the mechanism of action of FIE in treating cervical cancer. Cell cycle and apoptosis were detected by flow cytometry. The intracellular reactive oxygen species (ROS) level and the mitochondrial membrane potential were detected in HeLa cells treated with FIE. RT-PCR assays quantified the expression of apoptosis-related genes. Results and Discusssion: A total of 36 and 109 components were identified by GC-MS and LC-MS, respectively. Six active components, including 5-hydroxy-6,7-dimethoxyflavone, baicalein, cirsimaritin, epicatechin, luteolin, and 5,7-dihydroxy-6-methoxy2-phenylchromen-4-onem, were predicted by network pharmacology. The active components may affect the proliferation and apoptosis of HeLa cells through various cancer pathways, such as NF-kB and PI3K-Akt signaling pathways. FIE significantly inhibited colony formation in HeLa cells. We observed an increase in the total population of apoptotic cells and ROS content in HeLa cells. Further, the mitochondrial membrane potential of HeLa cells was significantly decreased. In HeLa cells, the expression levels of apoptosis-related genes, such as cytochrome C, caspase-3, caspase-9, and bax, were increased, while that of bcl-2 was decreased. Moreover, the ultrastructure of the cells exhibited apoptotic characteristics. Numerous vacuoles and the autophagic structure of the damaged mitochondrial organelles were observed in the cytoplasm of HeLa cells. Conclusions: Flavonoids of Elsholtzia densa Benth. showed clear inhibitory activity in HeLa cells and induced HeLa cell apoptosis through the mitochondrial endogenous apoptotic pathway. [ABSTRACT FROM AUTHOR]

Objectives Our previous study showed that resveratrol (Res) attenuates apoptosis and mitochondrial dysfunction in alveolar epithelial cell injury induced by hyperoxia by activating the SIRT1/PGC-1α signaling pathway. In the present study, we investigated whether Res protects against hyperoxia-induced lung injury in neonatal rats by activating SIRT1/PGC-1α signaling pathway. Methods Naturally delivered neonatal rats were randomly divided into six groups: normoxia + normal saline, normoxia + dimethyl sulfoxide (DMSO), normoxia + Res, hyperoxia + normal saline, hyperoxia + DMSO, and hyperoxia + Res. Lung tissue samples were collected on postnatal days 1, 7, and 14. Hematoxylin and eosin staining was used to evaluate lung development. Dual-immunofluorescence staining, real-time polymerase chain reaction, and western blotting were used to evaluate the levels of silencing information regulator 2-related enzyme 1 (SIRT1), peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α), nuclear respiratory factor 1 (Nrf1), Nrf2, transcription factor A (TFAM) and citrate synthase, the number of mitochondrial DNA (mtDNA) and mitochondria, the integrity of mtDNA, and the expression of TFAM in mitochondria. Results We found that hyperoxia insulted lung development, whereas Res attenuated the hyperoxia lung injury. Res significantly upregulated the levels of SIRT1, PGC-1α, Nrf1, Nrf2, TFAM, and citrate synthase; promoted TFAM expression in the mitochondria; and increased the copy number of ND1 and the ratio of ND4/ND1. Conclusion Our data suggest that Res attenuates hyperoxia-induced lung injury in neonatal rats, and this was achieved, in part, by activating the SIRT1/PGC-1α signaling pathway to promote mitochondrial biogenesis. Key Points Hyperoxia insulted lung development in neonatal rats. Resveratrol promoted mitochondrial biogenesis to attenuate hyperoxia lung injury in neonatal rats. Resveratrol, at least in part, promoted mitochondrial biogenesis by activating the SIRT1/PGC-1α signaling pathway. [ABSTRACT FROM AUTHOR]

Cinnamomi cortex was applied to mitigate joint injury since ancient China. However, the effect of Cinnamomi cortex on gouty arthritis (GA) was rarely reported. This study aimed to explore the effect of Cinnamomi cortex on monosodium urate (MSU)-induced acute GA (AGA) in rats, and clarify the underlying mechanism. The results showed that Cinnamomi cortex extract (CE) containing rich polyphenols and flavonoids alleviated joint swelling and inflammation by reducing programmed cell death in MSU-induced AGA rats. Network pharmacology analysis showed that CE's predictive inflammatory pathways included nuclear factor-κB (NF-κB) and necroptosis pathways. CE reduced expression of pyroptosis-related regulators including Gasdermin D and Caspase 1 via regulating NF-κB/NOD-like receptor thermal protein domain associated protein 3 signaling pathway in AGA rats. In conclusion, this study provided a theoretical basis for Cinnamomi cortex applied as a new veterinary medicine to protect against GA. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Cancer Biotherapy is the property of Editorial Office of Chinese Journal of Cancer Biotherapy and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Cervical spondylosis (CS) is a prevalent disorder that can have a major negative impact on quality of life. Traditional conservative treatment has limited efficacy, and electroacupuncture (EA) is a novel treatment option. We investigated the application and molecular mechanism of EA treatment in a rat model of cervical intervertebral disk degeneration (CIDD). Methods: The CIDD rat model was established, following which rats in the electroacupuncture (EA) group received EA. For overexpression of IL-22 or inhibition of JAK2-STAT3 signaling, the rats were injected intraperitoneally with recombinant IL-22 protein (p-IL-22) or the JAK2-STAT3 (Janus kinase 2—signal transducer and activator of transcription protein 3) inhibitor AG490 after model establishment. Rat nucleus pulposus (NP) cells were isolated and cultured. Cell counting kit-8 and flow cytometry were used to analyze the viability and apoptosis of the NP cells. Expression of IL-22, JAK2 and STAT3 was determined using RT-qPCR. Expression of IL-22/JAK2-STAT3 pathway and apoptosis related proteins was detected by Western blotting (WB). Results: EA protected the NP tissues of CIDD rats by regulating the IL-22/JAK2-STAT3 pathway. Overexpression of IL-22 significantly promoted the expression of tumor necrosis factor (TNF)-α, IL-6, IL-1β, matrix metalloproteinase (MMP)3 and MMP13 compared with the EA group. WB demonstrated that the expression of IL-22, p-JAK2, p-STAT3, caspase-3 and Bax in NP cells of the EA group was significantly reduced and Bcl-2 elevated compared with the model group. EA regulated cytokines and MMP through activation of IL-22/JAK2-STAT3 signaling in CIDD rat NP cells. Conclusion: We demonstrated that EA affected apoptosis by regulating the IL-22/JAK2-STAT3 pathway in NP cells and reducing inflammatory factors in the CIDD rat model. The results extend our knowledge of the mechanisms of action underlying the effects of EA as a potential treatment approach for CS in clinical practice. [ABSTRACT FROM AUTHOR]

Flavonoids are important secondary metabolites found in Juglans mandshurica Maxim., which is a precious reservoir of bioactive substances in China. To explore the antitumor actions of flavonoids (JMFs) from the waste branches of J. mandshurica, the following optimized purification parameters of JMFs by macroporous resins were first obtained. The loading concentration, flow rate, and loading volume of raw flavonoid extracts were 1.4 mg/mL, 2.4 BV/h, and 5 BV, respectively, and for desorption, 60% ethanol (4 BV) was selected to elute JMFs-loaded AB-8 resin at a flow rate of 2.4 BV/h. This adsorption behavior can be explained by the pseudo-second-order kinetic model and Langmuir isotherm model. Subsequently, JMFs were identified using Fourier transform infrared combined with high-performance liquid chromatography and tandem mass spectrometry, and a total of 156 flavonoids were identified. Furthermore, the inhibitory potential of JMFs on the proliferation, migration, and invasion of HepG2 cells was demonstrated. The results also show that exposure to JMFs induced apoptotic cell death, which might be associated with extrinsic and intrinsic pathways. Additionally, flow cytometry detection found that JMFs exposure triggered S phase arrest and the generation of reactive oxygen species in HepG2 cells. These findings suggest that the JMFs purified in this study represent great potential for the treatment of liver cancer. [ABSTRACT FROM AUTHOR]

Cinnamomi cortex was applied to mitigate joint injury since ancient China. However, the effect of Cinnamomi cortex on gouty arthritis (GA) was rarely reported. This study aimed to explore the effect of Cinnamomi cortex on monosodium urate (MSU)-induced acute GA (AGA) in rats, and clarify the underlying mechanism. The results showed that Cinnamomi cortex extract (CE) containing rich polyphenols and flavonoids alleviated joint swelling and inflammation by reducing programmed cell death in MSU-induced AGA rats. Network pharmacology analysis showed that CE's predictive inflammatory pathways included nuclear factor-xB (NF-kB) and necroptosis pathways. CE reduced expression of pyroptosis-related regulators including Gasdermin D and Caspase 1 via regulating NF-xB/NOD-like receptor thermal protein domain associated protein 3 signaling pathway in AGA rats. In conclusion, this study provided a theoretical basis for Cinnamomi cortex applied as a new veterinary medicine to protect against GA. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of ginsenoside Rb1 (Gn-Rb1) on oxeiptosis in hepatocellular carcinoma (HCC) HepG2 cells and its possible molecular mechanism. Methods: Bioinformatic was used to analyse the effect of the expression of PGAM5, a key gene of oxeiptosis, on the survival time of HCC patients. HCC tissues and paracancerous tissues of 8 HCC patients admitted into Liaoning Provincial Tumor Hospital were selected, and the expressions of oxeiptosis-related gene proteins and mRNAs were detected by WB assay and qPCR. HepG2 cells were randomly divided into the control group and the Gn-Rb1 group (intervened with 200 µmol/L Gn-Rb1). The effects of Gn-Rb1 on the colony formation ability and the migration ability of HepG2 cells were detected by the cell clone formation assay and the cell scratch assay, respectively. ELISA was used to detect the effect on the level of ROS. Microplate was used to detect the effect on the level of LDH; the effects of Gn-Rb1 on the expressions of key gene proteins and mRNAs were detected by WB assay and qPCR. Results: Bioinformatic analysis revealed that, compared with low-expression patients, patients with PGAM5 high-expression hepatocellular carcinoma had longer overall survival time (P<0.05). In clinical hepatocellular carcinoma and paracancerous tissue samples, it was found that compared with paracancerous tissues, at protein and mRNA levels, the expressions of KEAP1 and PGAM5 in tumor tissues were significantly lower; the expression of NRF2 was significantly higher (all P<0.01); and the expression of p-AIFM1 was significantly higher (P<0.05). After HepG2 cells were intervened with 200 µmol/L Gn-Rb1, compared with those in the control group, the migratory and colony-forming abilities of HepG2 cells in the Gn-Rb1 group reduced significantly (all P<0.01), and the level of LDH increased significantly (P<0.05). Compared with the control group, at mRNA and protein levels, the expressions of KEAP1 and PGAM5 in the Gn-Rb1 group were significantly higher (all P<0.05); the expression of NRF2 was significantly lower (all P<0.05); and the expression of p-AIFM1 protein was significantly lower (P<0.01). Conclusion: Oxeiptosis is inhibited in hepatocellular carcinoma tissues, and Gn-Rb1 promotes oxeiptosis in HCC HepG2 cells by regulating the KEAP1/PGAM5/AIFM1 pathway, thus suppressing the proliferation and migration abilities of HepG2 cells. [ABSTRACT FROM AUTHOR]

Background: Spinal cord injury (SCI) can result in structural and functional damage to the spinal cord, which may lead to loss of limb movement and sensation, loss of bowel and bladder control, and other complications. Previous studies have revealed the critical influence of trans-acting transcription factor 1 (SP1) in neurological pathologies, however, its role and mechanism in SCI have not been fully studied. Methods: The study was performed using mouse microglia BV2 stimulated using lipopolysaccharide (LPS) and male adult mice subjected to spinal hitting. Western blotting was performed to detect protein expression of SP1, 5-hydroxytryptamine (serotonin) receptor 2B (HTR2B), BCL2-associated x protein (Bax), B-cell lymphoma-2 (Bcl-2), inducible nitric oxide synthase (iNOS), clusters of differentiation 86 (CD86), Arginase 1 (Arg-1) and clusters of differentiation 206 (CD206). Cell viability and apoptosis were analyzed by MTT assay and TUNEL assay. mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-4 (IL-4) and tumor necrosis factor-β (TNF-β) were quantified by quantitative real-time polymerase chain reaction. The association of SP1 and HTR2B was identified by chromatin immunoprecipitation assay and dual-luciferase reporter assay. HE staining assay was performed to analyze the pathological conditions of spinal cord tissues. Results: LPS treatment induced cell apoptosis and inhibited microglia polarization from M1 to M2 phenotype, accompanied by an increase of Bax protein expression and a decrease of Bcl-2 protein expression, however, these effects were relieved after SP1 silencing. Mechanism assays revealed that SP1 transcriptionally activated HTR2B in BV2 cells, and HTR2B knockdown rescued LPS-induced effects on BV2 cell apoptosis and microglial M1/M2 polarization. Moreover, SP1 absence inhibited BV2 cell apoptosis and promoted microglia polarization from M1 to M2 phenotype by decreasing HTR2B expression. SCI mouse model assay further showed that SP1 downregulation could attenuate spinal hitting-induced promoting effects on cell apoptosis of spinal cord tissues and microglial M1 polarization. Conclusion: SP1 transcriptionally activated HTR2B to aggravate traumatic SCI by shifting microglial M1/M2 polarization. [ABSTRACT FROM AUTHOR]

Camellia oleifera is a medicine food homology plant widely cultivated in the Yangtze River Basin and southern China due to its camellia oil. Camellia oleifera bud and fruit exist simultaneously, and its bud is largely discarded as waste. However, C. oleifera bud has been used in traditional Chinese medicine to treat a variety of ailments. Thus, the purpose of this study was to identify the chemical components of C. oleifera bud ethanol extract (EE) and first evaluate its anticancer effects in non-small cell lung cancer A549 cells. Based on UHPLCQ-Orbitrap-MS analysis, seventy components were identified. For anticancer activity, C. oleifera bud EE had remarkable cytotoxic effect on non-small cell lung cancer A549 (IC50: 57.53 ± 1.54 µg/mL) and NCI-H1299 (IC50: 131.67 ± 4.32 µg/ mL) cells, while showed lower cytotoxicity on non-cancerous MRC-5 (IC50 > 320 µg/mL) and L929 (IC50: 179.84 ± 1.08 µg/mL) cells. It dramatically inhibited the proliferation of A549 cells by inducing cell cycle arrest at the G1 phase. Additionally, it induced apoptosis in A549 cells through a mitochondria-mediated pathway, which decreased mitochondrial membrane potential, upregulated Bax, activated caspase 9 and caspase 3, and resulted in PARP cleavage. Wound healing and transwell invasion assays demonstrated that C. oleifera bud EE inhibited the migration and invasion of A549 cells in a dose-dependent manner. The above findings indicated that C. oleifera bud EE revealed notable anticancer effects by inhibiting proliferation, inducing apoptosis, and suppressing migration and invasion of A549 cells. Hence, C. oleifera bud ethanol extract could serve as a new source of natural anticancer drugs. [ABSTRACT FROM AUTHOR]

Lung cancer is a major public health issue and heavy burden in China and worldwide due to its high incidence and mortality without effective treatment. It's imperative to develop new treatments to overcome drug resistance. Natural products from food source, given their wide-ranging and long-term benefits, have been increasingly used in tumor prevention and treatment. This study revealed that Hibiscus manihot L. flower extract (HML) suppressed the proliferation and migration of A549 cells in a dose and time dependent manner and disrupting cell cycle progression. HML markedly enhanced the accumulation of ROS, stimulated the dissipation of mitochondrial membrane potential (MMP) and that facilitated mitophagy through the loss of mitochondrial function. In addition, HML induced apoptosis by activation of the PTEN-P53 pathway and inhibition of ATG5/7-dependent autophagy induced by PINK1-mediated mitophagy in A549 cells. Moreover, HML exert anticancer effects together with 5-FU through synergistic effect. Taken together, HML may serve as a potential tumor prevention and adjuvant treatment for its functional attributes. [ABSTRACT FROM AUTHOR]

Aponermin (沙艾特) is a recombinant circularly permuted human tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) developed by Beijing Sunbio Biotech (a wholly owned subsidiary of Wuhan Hiteck Biological Pharma CO., LTD) for the treatment of multiple myeloma. Aponermin binds to and activates the death receptors 4 and/or 5 on tumour cells, triggering intracellular caspase reactions and inducing apoptosis, thereby exerting antitumor effects. In November 2023, aponermin in combination with thalidomide and dexamethasone received its first approval in China for the treatment of patients with relapsed or refractory multiple myeloma who have received at least two prior therapies. This article summarizes the milestones in the development of aponermin leading to this first approval for relapsed or refractory multiple myeloma. [ABSTRACT FROM AUTHOR]

The present study compares sugarcane-wax purified policosanols sourced from Cuba (Raydel®) and China (BOC Sciences) and utilized following the synthesis of reconstituted high-density lipoproteins (rHDL). The two policosanols exhibited distinctly different ingredient ratios of long-chain aliphatic alcohols, particularly 1-octacosanol (C28) and 1-tetratriacotanol (C34). After synthesizing rHDL with apolipoprotein A-I (apoA-I), the two policosanols bound well with phospholipid and apoA-I to form the discoidal rHDL. Notably, rHDL-1, containing Cuban policosanol, displayed the largest particle diameter at approximately 78 ± 3 nm. In contrast, both control rHDL (rHDL-0) and rHDL containing Chinese policosanol (rHDL-2) exhibited smaller particles, with diameters of approximately 58 ± 3 nm and 61 ± 2 nm, respectively. Furthermore, rHDL-1 demonstrated enhanced anti-glycation activity, safeguarding apoA-I from degradation within HDL, and displayed the antioxidant ability to inhibit LDL oxidation. A microinjection of each rHDL into zebrafish embryos in the presence of carboxymethyllysine (CML) revealed rHDL-1 to have the strongest antioxidant activity with the highest embryo survivability and normal developmental morphology. Dermal application to recover the wound revealed rHDL-1 to have the highest wound-healing activity (75%) and survivability (92%) in the cutaneous wound area in the presence of CML. In adult zebrafish, injecting CML (250 μg) caused acute death and hyperinflammation, marked by heightened neutrophil infiltration and interleukin (IL)-6 production in liver. However, co-administering rHDL-1 notably increased survival (85%) and exhibited strong anti-inflammatory properties, reducing IL-6 production while improving the blood lipid profile. However, a co-injection of rHDL-2 resulted in the lowest survivability (47%) with more hepatic inflammation. In conclusion, Cuban policosanol (Raydel®) has more desirable properties for the in vitro synthesis of rHDL with stronger anti-glycation and antioxidant activities than those of Chinese policosanol (BOC Sciences). Moreover, Raydel-policosanol-integrated rHDL demonstrates a noteworthy effect on accelerated wound healing and robust anti-inflammatory properties, leading to increased survivability in zebrafish embryos and adults by effectively suppressing CML-induced hyperinflammation. [ABSTRACT FROM AUTHOR]

To alleviate the growth inhibition, and intestinal damage of Chinese mitten crab (Eriocheir sinensis) induced by low fishmeal diets (LF), an 8-week feeding trial was conducted to evaluate the addition of dietary soybean-derived bioactive peptides (SBP) in LF diets on the regulation of growth, digestion and intestinal health. The crabs were fed isonitrogenous and isoenergetic conventional diet and LF diets (10 % fishmeal replaced by soybean meal, LF) supplemented with 0, 1 %, 2 %, 4 % and 6 % SBP, respectively. The results showed that LF diet inhibited growth while inclusion of SBP quadratically remitted the growth inhibition induced by LF. For digestive function, increasing addition level of SBP quadratically improved the α -amylase and trypsin activities. For antioxidant function, LF group significantly increased the malondialdehyde content, while SBP linearly decreased the malondialdehyde level and cubically increased the anti-superoxide anion activity and total antioxidant capacity level. For intestinal health, the peritrophic membrane (PM) almost completely separated from the inner wall of the intestinal lumen, the epithelial cells reduced, the muscularis became thinner and the apoptotic signals increased in LF group; with SBP addition, the intestinal morphology was improved, with the PM adhering to the inner wall of the intestinal lumen, an increase in the number of epithelial cells and an increase in the thickness of the muscularis. Additionally, there was a decrease in apoptotic signals. Dietary SBP also increased the expression of PT and Crustin1 quadratically and decreased the expression of ALF1 linearly, ALF3 and ILF2 quadratically. [ABSTRACT FROM AUTHOR]

Que Zui tea (QT) is an important herbal tea in the diet of the 'Yi' people, an ethnic group in China, and it has shown significant antioxidant, anti-inflammatory, and hepatoprotective effects in vitro. This study aims to explore the protective effects of the aqueous-ethanol extract (QE) taken from QT against ᴅ-galactose (ᴅ-gal)-induced oxidative stress damage in mice and its potential mechanisms. QE was identified as UHPLC-HRMS/MS for its chemical composition and possible bioactive substances. Thus, QE is rich in phenolic and flavonoid compounds. Twelve compounds were identified, the main components of which were chlorogenic acid, quinic acid, and 6′-O-caffeoylarbutin. Histopathological and biochemical analysis revealed that QE significantly alleviated brain, liver, and kidney damage in ᴅ-gal-treated mice. Moreover, QE remarkably attenuated oxidative stress by activating the Nrf2/HO-1 pathway to increase the expression of antioxidant indexes, including GSH, GSH-Px, CAT, SOD, and T-AOC. In addition, QE administration could inhibit the IL-1β and IL-6 levels, which suppress the inflammatory response. QE could noticeably alleviate apoptosis by inhibiting the expressions of Caspase-3 and Bax proteins in the brains, livers, and kidneys of mice. The anti-apoptosis mechanism may be related to the upregulation of the SIRT1 protein and the downregulation of the p53 protein induced by QE in the brain, liver, and kidney tissues of mice. Molecular docking analysis demonstrated that the main components of QE, 6′-O-caffeoylarbutin, chlorogenic acid, quinic acid, and robustaside A, had good binding ability with Nrf2 and SIRT1 proteins. The present study indicated that QE could alleviate ᴅ-gal-induced brain, liver and kidney damage in mice by inhibiting the oxidative stress and cell apoptosis; additionally, the potential mechanism may be associated with the SIRT1/Nrf2 signaling pathway. [ABSTRACT FROM AUTHOR]

Ovarian cancer is a common, highly lethal tumor. Herein, we reported that S-phase kinase-associated protein 2 (Skp2) is essential for the growth and aerobic glycolysis of ovarian cancer cells. Skp2 was upregulated in ovarian cancer tissues and associated with poor clinical outcomes. Using a customized natural product library screening, we found that xanthohumol inhibited aerobic glycolysis and cell viability of ovarian cancer cells. Xanthohumol facilitated the interaction between E3 ligase Cdh1 and Skp2 and promoted the Ub-K48-linked polyubiquitination of Skp2 and degradation. Cdh1 depletion reversed xanthohumol-induced Skp2 downregulation, enhancing HK2 expression and glycolysis in ovarian cancer cells. Finally, a xenograft tumor model was employed to examine the antitumor efficacy of xanthohumol in vivo. Collectively, we discovered that xanthohumol promotes the binding between Skp2 and Cdh1 to suppress the Skp2/AKT/HK2 signal pathway and exhibits potential antitumor activity for ovarian cancer cells. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Cancer Biotherapy is the property of Editorial Office of Chinese Journal of Cancer Biotherapy and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Duck Tembusu virus (DTMUV) is an emerging mosquito-borne flavivirus that infects mainly poultry and has caused huge economic losses to the poultry farming industry in China. Also known as duck hemorrhagic ovarian disease, DTMUV principally destroys ovarian tissue in ducks, causing a dramatic drop in egg production. and can also invade the male reproductive system causing lesions. Currently, little research has been done to reveal the underlying mechanisms of reproductive dysfunction in ducks caused by DTMUV infection. In this study, histopathological analysis and electron microscopy of testes of ducks infected with DTMUV showed that DTMUV caused testicular atrophy and cytoplasmic vacuolation in ducks. Terminal Deoxynucleotidyl Transferase-Mediated Nick-End Labeling (TUNEL) staining and real-time quantitative PCR(RT-qPCR) results further indicated that DTMUV induced spermatogenic cells apoptosis. After DTMUV infection, a large amount of cytochrome c (Cytc) was released from the mitochondrial matrix into the cytoplasm, activating downstream target proteins and causing apoptosis. To sum up, DTMUV induces spermatogenic cell apoptosis through the Cytc-induced mitochondrial apoptosis pathway, our study provides evidence for DTMUV infection-induced male reproductive disorders. • DTMUV infection led to vacuolation in spermatogenic cells. • DTMUV infection induced apoptosis in spermatogenic cells. • Apoptosis in spermatogenic cells is regulated by multiple apoptotic pathways. • DTMUV infection activates caspase family proteins and promotes the release of Cytc from mitochondria. [ABSTRACT FROM AUTHOR]

The family Lauraceae includes various genus in which Litsea has around 200-400 varieties which are widely scattered in the tropical and semi-tropical zones. In China, Litsea species are used traditionally in many disease conditions such as bone pain, diarrhoea, edema, dyspepsia, gastroenteritis and colds. Litsea glutinosa has been traditionally used in the treatment of tumors by the local people of Chittagong Hill Tracts, Bangladesh. Also, 15 other Litsea species are reported to have cytotoxic activity against various cancer cell lines, making this genus a promising potential source of anticancer compounds. This review provides comprehensive information about the cytotoxicity potential of various species in the genus Litsea along with secondary metabolites responsible, and its potential utility in lung, breast, hepatocellular, ovarian, prostate, colon and cervical cancer therapeutics as a botanical product. The published cytotoxicity data of these plants are mainly based on in vitro studies with very few molecular levels and mechanistic studies conducted. The optimistic results of these 16 species open unexplored vistas of natural product chemistry and the anticancer potential of this genus. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What is the mechanism behind cryoinjury in human sperm, particularly concerning the interplay between reactive oxygen species (ROS) and autophagy, and how does it subsequently affect sperm fate? SUMMARY ANSWER The freeze-thaw operation induces oxidative stress by generating abundant ROS, which impairs sperm motility and activates autophagy, ultimately guiding the sperm toward programmed cell death such as apoptosis and necrosis, as well as triggering premature capacitation. WHAT IS KNOWN ALREADY Both ROS-induced oxidative stress and autophagy are thought to exert an influence on the quality of frozen-thawed sperm. STUDY DESIGN, SIZE, DURATION Overall, 84 semen specimens were collected from young healthy fertile males, with careful quality evaluation. The specimens were split into three groups to investigate the ROS-induced cryoinjury: normal control without any treatment, sperm treated with 0.5 mM hydrogen peroxide (H2O2) for 1 h, and sperm thawed following cryopreservation. Samples from 48 individuals underwent computer-assisted human sperm analysis (CASA) to evaluate sperm quality in response to the treatments. Semen samples from three donors were analyzed for changes in the sperm proteome after H2O2 treatment, and another set of samples from three donors were analyzed for changes following the freeze-thaw process. The other 30 samples were used for fluorescence-staining and western blotting. PARTICIPANTS/MATERIALS, SETTING, METHODS Sperm motility parameters, including progressive motility (PR %) and total motility (PR + NP %), were evaluated using the CASA system on a minimum of 200 spermatozoa. The proteomic profiles were determined with label-free mass spectrometry (MS/MS) and protein identification was performed via ion search against the NCBI human database. Subsequently, comprehensive bioinformatics was applied to detect significant proteomic changes and functional enrichment. Fluorescence-staining and western blot analyses were also conducted to confirm the proteomic changes on selected key proteins. The ROS level was measured using 2′,7′-dichlorodihydrofluorescein diacetate labeling and the abundance of bioactive mitochondria was determined by evaluating the inner mitochondrial membrane potential (MMP) level. Molecular behaviors of sequestosome-1 (p62 or SQSTM1) and microtubule-associated proteins 1A/1B light chain 3 (LC3) were monitored to evaluate the state of apoptosis in human sperm. Fluorescent probes oxazole yellow (YO-PRO-1) and propidium iodide (PI) were utilized to monitor programmed cell death, namely apoptosis and necrosis. Additionally, gradient concentrations of antioxidant coenzyme Q10 (CoQ10) were introduced to suppress ROS impacts on sperm. MAIN RESULTS AND THE ROLE OF CHANCE The CASA analysis revealed a significant decrease in sperm motility for both the H2O2-treatment and freeze-thaw groups. Fluorescence staining showed that high ROS levels were produced in the treated sperm and the MMPs were largely reduced. The introduction of CoQ10 at concentrations of 20 and 30 μM resulted in a significant rescue of progressive motility (P  < 0.05). The result suggested that excessive ROS could be the major cause of sperm motility impairment, likely by damaging mitochondrial energy generation. Autophagy was significantly activated in sperm when they were under oxidative stress, as evidenced by the upregulation of p62 and the increased conversion of LC3 as well as the upregulation of several autophagy-related proteins, such as charged multivesicular body protein 2a, mitochondrial import receptor subunit TOM22 homolog, and WD repeat domain phosphoinositide-interacting protein 2. Additionally, fluorescent staining indicated the occurrence of apoptosis and necrosis in both H2O2-treated sperm and post-thaw sperm. The cell death process can be suppressed when CoQ10 is introduced, which consolidates the view that ROS could be the major contributor to sperm cryoinjury. The freeze-thaw process could also initiate sperm premature capacitation, demonstrated by the prominent increase in tyrosine phosphorylated proteins, verified with anti-phosphotyrosine antibody and immunofluorescence assays. The upregulation of capacitation-related proteins, such as hyaluronidase 3 and Folate receptor alpha, supported this finding. LARGE SCALE DATA The data underlying this article are available in the article and its online supplementary material. LIMITATIONS, REASONS FOR CAUTION The semen samples were obtained exclusively from young, healthy, and fertile males with progressive motility exceeding 60%, which might overemphasize the positive effects while possibly neglecting the negative impacts of cryoinjury. Additionally, the H2O2 treatment conditions in this study may not precisely mimic the oxidative stress experienced by sperm after thawing from cryopreservation, potentially resulting in the omission of certain molecular alterations. WIDER IMPLICATIONS OF THE FINDINGS This study provides substantial proteomic data for a comprehensive and deeper understanding of the impact of cryopreservation on sperm quality. It will facilitate the design of optimal protocols for utilizing cryopreserved sperm to improve applications, such as ART, and help resolve various adverse situations caused by chemotherapy, radiotherapy, and surgery. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by grants from the Major Innovation Project of Research Institute of National Health Commission (#2022GJZD01-3) and the National Key R&D Program of China (#2018YFC1003600). All authors declare no competing interests. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

PANoptosis has recently been discovered as a new type of cell death. PANoptosis mainly refers to the significant interaction among the three programmed cell death pathways of apoptosis, necroptosis, and pyroptosis. Despite this, only a few studies have examined the systematic literature in this area. By analyzing the bibliometric data for PANoptosis, we can visualize the current hotspots and predicted trends in research. This study analyzed bibliometric indicators using the Histcite Pro 2.0 tool, which searches the Web of Science for PANoptosis literature published between 2016 and 2022. A bibliometric analysis was performed using Histcite Pro 2.0, while research trends and hotspots were visualized using VOSviewer, CiteSpace and BioBERT. The output of related literature was low in the four years from the first presentation of PANoptosis in 2016 to 2020. The volume of relevant literature grew exponentially between 2020 and 2022. The United States and China play a leading role in this field. Although China started late, its research in this field is developing rapidly. As research progressed, more focus was placed on the relationship between PANoptosis and pyroptosis, as well as apoptosis and necrosis. Now is a rapid development stage of PANoptosis research. Most of the research focuses on the cellular level, and the focus is more on the treatment of tumor-related diseases. The current focus of this area is PANoptosis mechanisms in cancer and inflammation. It can be seen from the burst analysis of keywords that caspase1 and host defense have consistently been research hotspots in the field of PANoptosis, while the frequency of NLRC4, causes of autoinflammation, recognition, NLRP3, and Gasdermin D has gradually increased, all of which have become research hotspots in recent years. Finally, we used the BioBERT biomedical language model to mine the most documented genes and diseases in the PANoptosis field articles, pointing out the direction for subsequent research steps. According to a bibliometric analysis, researchers have shown an increased interest in PANoptosis over the past few years. Researchers initially focused on the molecular mechanism of PANoptosis and pyroptosis, apoptosis, and necroptosis. The role of PANoptosis in diseases and conditions such as inflammation and tumors is one of the current research hotspots in this area. The focus is more on treating inflammation-related diseases, which will become the key development direction of future research. [ABSTRACT FROM AUTHOR]

Background: Apoptosis after spinal cord injury (SCI) plays a pivotal role in the secondary injury mechanisms, which cause the ultimate neurologic insults. A better understanding of the molecular and cellular basis of apoptosis in SCI allows for improved glial and neuronal survival via the administrations of anti-apoptotic biomarkers. The knowledge structure, development trends, and research hotspots of apoptosis and SCI have not yet been systematically investigated. Methods: Articles and reviews on apoptosis and SCI, published from 1st January 1994 to 1st Oct 2023, were retrieved from the Web of ScienceTM. Bibliometrix in R was used to evaluate annual publications, countries, affiliations, authors, sources, documents, key words, and hot topics. Results: A total of 3,359 publications in accordance with the criterions were obtained, which exhibited an ascending trend in annual publications. The most productive countries were the USA and China. Journal of Neurotrauma was the most impactive journal; Wenzhou Medical University was the most prolific affiliation; Cuzzocrea S was the most productive and influential author. "Apoptosis," "spinal-cord-injury," "expression," "activation," and "functional recovery" were the most frequent key words. Additionally, "transplantation," "mesenchymal stemness-cells," "therapies," "activation," "regeneration," "repair," "autophagy," "exosomes," "nlrp3 inflammasome," "neuroinflammation," and "knockdown" were the latest emerging key words, which may inform the hottest themes. Conclusions: Apoptosis after SCI may cause the ultimate neurological damages. Development of novel treatments for secondary SCI mainly depends on a better understanding of apoptosis-related mechanisms in molecular and cellular levels. Such therapeutic interventions involve the application of anti-apoptotic agents, free radical scavengers, as well as anti-inflammatory drugs, which can be targeted to inhibit core events in cellular and molecular injury cascades pathway. [ABSTRACT FROM AUTHOR]

Background: Spinal cord injury (SCI) is a severe central nervous trauma that can cause serious consequences. Cell death is emerging as a common pathogenesis after SCI. In the last two decades, numerous studies have been published in the field of cell death after SCI. However, it is still rare to find relevant bibliometric analyses. This bibliometric study aims to visually represent global research trends in the field of cell death after SCI. Methods: Bibliometric data were sourced from the Web of Science Core Collection (WoSCC) database. VOSviewer, CiteSpace, and R software ("bibliometrix" package) were used to analyze and visualize bibliometric data. Annual scientific production, countries/regions, institutions, authors, journals, highly cited papers, keywords, and literature co-citation were evaluated to determine research performance. Results: An analysis of 5,078 publications extracted from the WoSCC database revealed a fluctuating yet persistent growth in the field of cell death after SCI over the past 23 years. China and the United States, contributing 69% of the total publications, were the main driving force in this field. The Wenzhou Medical University from China contributed to the most papers. In terms of authors, Salvatore Cuzzocrea from the University of Messina had the highest number of publications. The "Journal of Neurotrauma" was the top journal in terms of the number of publications, however, the "Journal of Neuroscience" was the top journal in terms of the number of citations. The theme of the highly cited articles mainly focused on the mechanism of cell death after SCI. The keyword and literature co-citation analysis mainly focused on the mode of cell death, mechanism research of cell death, and functional recovery after SCI. Conclusion: This study analyzes the research hotspots, frontiers, and development trends in the field of cell death after SCI, which is important for future studies. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a malignant tumor originating in the nasopharyngeal epithelium with a high incidence in southern China and parts of Southeast Asia. The current treatment methods are mainly radiotherapy and chemotherapy. However, they often have side effects and are not suitable for long‐term exposure. Natural products have received more and more attention in cancer prevention and treatment because of their its high efficiency, low toxic side effects, and low toxicity. Natural products can serve as a viable alternative, and this study aimed to review the efficacy and mechanisms of natural products in the treatment of NPC by examining previous literature. Most natural products act by inhibiting cell proliferation, metastasis, inducing cell cycle arrest, and apoptosis. Although further research is needed to verify their effectiveness and safety, natural products can significantly improve the treatment of NPC. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Cancer Biotherapy is the property of Editorial Office of Chinese Journal of Cancer Biotherapy and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata (PAC) and the underlying mechanism. Methods: B16F10 and 4T1 cells were cultured with PAC of 40 µg/mL, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with saline water, positive control group (LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. Results: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein (P<0.05), up-regulation of Caspase-3 protein (P<0.05) and ERK1 mRNA (P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. Conclusions: Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice. [ABSTRACT FROM AUTHOR]

Iodine is an essential nutrient that may change the occurrence of autoimmune thyroiditis (AIT). Apoptosis and DNA methylation participate in the pathogenesis and destructive mechanism of AIT. We detected the methylation and the expression of mRNA of intrinsic apoptosis-associated genes (YWHAG , ING4 , BRSK2 and GJA1) to identify the potential interactions between the levels of methylation in these genes and different levels of iodine. 176 adult patients with AIT in Shandong Province, China, were included. The MethylTargetTM assay was used to verify the levels of methylation. We used PCR to detect the mRNA levels of the candidate genes. Interactions between methylation levels of the candidate genes and iodine levels were evaluated with multiplicative and addictive interaction models and GMDR. In the AIT group, YWHAG_1 and six CpG sites and BRSK2_1 and eight CpG sites were hypermethylated, whereas ING4_1 and one CpG site were hypomethylated. A negative correlation was found between methylation levels of YWHAG and mRNA expression. The combination of iodine fortification, YWHAG_1 hypermethylation and BRSK2_1 hypermethylation was significantly associated with elevated AIT risk. A four-locus model (YWHAG_1 × ING4_1 × BRSK2_1 × iodine level) was found to be the best model of the gene–environment interactions. We identified abnormal changes in the methylation status of YWHAG , ING4 and BRSK2 in patients with AIT in different iodine levels. Iodine fortification not only affected the methylation levels of YWHAG and BRSK2 but also interacted with the methylation levels of these genes and may ultimately increase the risk of AIT. [ABSTRACT FROM AUTHOR]

p53 is arguably one of the most important tumor suppressor genes in humans. Due to the paramount importance of p53 in the onset of cell cycle arrest and apoptosis, the p53 gene is found either silenced or mutated in the vast majority of cancers. Furthermore, activated wild-type p53 exhibits a strong bystander effect, thereby activating apoptosis in surrounding cells without being physically present there. For these reasons, p53-targeted therapy that is designed to restore the function of wild-type p53 in cancer cells seems to be a very appealing therapeutic approach. Systemic delivery of p53-coding DNA or RNA using nanoparticles proved to be feasible both in vitro and in vivo. In fact, one p53-based therapeutic (gendicine) is currently approved for commercial use in China. However, the broad use of p53-based therapy in p53-inactivated cancers is severely restricted by its inadequate efficacy. This review highlights the current state-of-the-art in this area of biomedical research and also discusses novel approaches that may help overcome the shortcomings of p53-targeting nanomedicine. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the most common form of liver cancer. Circular RNAs (circRNAs) play a vital role in cancer development and progression. This study investigated the role and potential mechanism of circRNA filamin binding LIM protein 1 (circFBLIM1) in HCC. Methods: Exosomes were identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot assay. The levels of circFBLIM1, miR-338, and low-density lipoprotein receptor-related protein 6 (LRP6) were measured by quantitative real-time polymerase chain reaction or Western blot. Glycolysis was analyzed by detecting glucose consumption, lactate production, ATP level, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR). Cell viability was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Cell apoptosis was detected by flow cytometry. Xenograft assay was performed to analyze tumor growth in vivo. The interaction among circFBLIM1, miR-338, and LRP6 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. This study was approved by the Institutional Review Board of the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine. Results: CircFBLIM1 was highly expressed in HCC serum exosomes and HCC cells. Inhibition of circFBLIM1 confined HCC glycolysis and progression. CircFBLIM1 knockdown blocked tumorigenesis in vivo. CircFBLIM1 was a sponge of miR-338 and promoted HCC progression and glycolysis by regulating miR-338. Moreover, miR-338 suppressed HCC progression and glycolysis via targeting LRP6. Mechanistically, circFBLIM1 functioned as an miR-338 sponge to upregulate LRP6. Conclusion: CircFBLIM1 facilitated HCC progression and glycolysis via modulating the miR-338/LRP6 axis, which may provide promising therapeutic targets for HCC. [ABSTRACT FROM AUTHOR]

The nasopharyngeal epithelium, which is frequently found in Southeast Asia and Southern China, gives rise to nasopharyngeal carcinoma (NPC). Despite improvements in diagnostic tools and remedial modalities, the prognosis of NPC remains meager. Thus, innovative and effective anti-cancer agents are desirable. Voacangine (VCG) is a recognized alkaloid sequestered from the plant Voacanga foetida. Hence, the current research assessed the anti-proliferative and apoptotic action of VCG on HK-1 human NPC cells and its underlying molecular actions. The results exposed that VCG (20 and 25 µ/ml) avert the HK-1 cells proliferation, which stimulates apoptosis by the amelioration of Bcl-2-associated X protein (Bax) and caspases, while it lessens cyclin-D1, B-cell lymphoma 2 (Bcl-2), c-Myc, survivin in a dose-dependent way. Furthermore, VCG alleviates inflammation, cell proliferation, and augmented cell death through the attenuation of Nuclear factor kappa B (NF-κB) facilitated Phosphoinositide 3-kinase/Protein kinase B/Mammalian target of rapamycin (PI3K/AKT/mTOR) signaling. This creates a Bax/Bcl-2 proportion imbalance, which triggers caspases cascade, Cyt-c, and induces apoptosis. Our findings deliver novel perceptions into exploring VCG as a beneficial bioactive alkaloid for the handling of NPC. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal carcinoma (NPC), predominant in Southern China and Southeast Asia, is a malignant tumor that arises from the epithelial lining of the nasopharynx. Current NPC treatments result in unfavorable side effects. Natural compounds with anti-proliferative capabilities are gaining popularity as a way to mitigate the toxicity of radiation and synthetic antitumor drugs. Ponicidin, an ent-kaurane diterpenoid, has been demonstrated to possess several pharmacological activities, including antitumor, antibacterial, immunoregulatory, antiviral, and anti-inflammatory properties. Materials and Methods: In the current investigation, the anti-carcinogenic activity of Ponicidin against nasopharyngeal cell line C666-1, has been investigated. The influence of Ponicidin on cell viability, apoptotic induction, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation, and apoptotic markers has been examined. Doxorubicin was selected as the positive control for the experiments. Results: The effect of Ponicidin on the viability of C666-1 cells revealed that its cytotoxic potential increased in a dose-dependent pattern and the optimum concentration chosen for further experiments was 7.5 µM. The Ponicidin-treated cells demonstrated a significant increase in the amount of TBARS, whereas it reduced the activity of superoxide dismutase (SOD) and glutathione (GSH) levels, indicating augmented oxidative stress and lower antioxidant activity in the C666-1 cells. The acridine orange/ethidium bromide (AO/EtBr) staining technique was used to assess morphological changes with respect to apoptosis, which confirmed its apoptotic nature. Furthermore, Ponicidin elevated the ROS generation, modified the mitochondrial membrane permeability, elevated the apoptotic marker levels (caspase-3, caspase-9, and Bax) and reduced the Bcl-2 expression in C666-1 cell lines. Conclusion: The findings suggest that Ponicidin successfully inhibited cancer cell proliferation by following the mitochondrial apoptotic pathway and thus could be effectively utilized as a potent anti-cancer agent for the treatment of nasopharyngeal cancer. [ABSTRACT FROM AUTHOR]

Background: This study investigated the effect of uteroplacental insufficiency (UPI) on renal development by detecting metabolic alterations in the kidneys of rats with intrauterine growth restriction (IUGR). Methods: On gestational day 17, pregnant Sprague Dawley rats were selected and allocated randomly to either the IUGR group or the control group. The IUGR group received a protocol involving the closure of bilateral uterine vessels, while the control group underwent a sham surgery. The rat pups were delivered on gestational day 22 by natural means. Pups were randomly recruited from both the control and IUGR groups on the seventh day after birth. The kidneys were surgically removed to conduct Western blot and metabolomic analyses. Results: IUGR was produced by UPI, as evidenced by the significantly lower body weights of the pups with IUGR compared to the control pups on postnatal day 7. UPI significantly increased the levels of cleaved caspase-3 (p < 0.05) and BAX/Bcl-2 (p < 0.01) in the pups with IUGR. Ten metabolites exhibited statistically significant differences between the groups (q < 0.05). Metabolic pathway enrichment analysis demonstrated statistically significant variations between the groups in the metabolism related to fructose and mannose, amino and nucleotide sugars, and inositol phosphate. Conclusions: UPI alters kidney metabolism in growth-restricted newborn rats and induces renal apoptosis. The results of our study have the potential to provide new insights into biomarkers and metabolic pathways that are involved in the kidney changes generated by IUGR. [ABSTRACT FROM AUTHOR]

Cisplatin (Cis) is considered to be one of the most effective drugs for killing cancer cells and remains a first-line chemotherapeutic agent. However, Cis's multiple toxicities (especially nephrotoxicity) have limited its clinical use. Marsdenia tenacissima (Roxb.) Wight et Arn. (MT), a traditional Chinese medicine (TCM) employed extensively in China, not only enhances the antitumor effect in combination with Cis, but is also used for its detoxifying effect, as it reduces the toxic side effects of chemotherapy drugs. The aim of this study was to explore the therapeutic effect of MT on Cis-induced nephrotoxicity, along with its underlying mechanisms. In this study, liquid–mass spectrometry was performed to identify the complex composition of the extracts of MT. In addition, we measured the renal function, antioxidant enzymes, and inflammatory cytokines in mice with Cis-induced nephrotoxicity and conducted renal histology evaluations to assess renal injury. The expressions of the proteins related to antioxidant, anti-inflammatory, and apoptotic markers in renal tissues was detected by Western blotting (WB). MT treatment improved the renal function, decreased the mRNA expression of the inflammatory factors, and increased the antioxidant enzyme activity in mice. A better renal histology was observed after MT treatment. Further, MT inhibited the expression of the phospho-NFκB p65 protein/NFκB p65 protein (p-p65)/p65, phospho-inhibitor of nuclear factor kappa B kinase beta subunit/inhibitor of nuclear factor kappa B kinase beta subunit (p-IKKβ/IKKβ), Bcl-2-associated X (Bax), and Cleaved Caspase 3/Caspase 3 proteins, while the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Recombinant NADH Dehydrogenase, Quinone 1 (NQO1), and B-cell lymphoma-2 (Bcl-2) was increased. The present study showed that MT ameliorated renal injury, which mainly occurs through the regulation of the Nrf2 pathway, the NF-κB pathway, and the suppression of renal tissue apoptosis. It also suggests that MT can be used as an adjuvant to mitigate the nephrotoxicity of Cis chemotherapy. [ABSTRACT FROM AUTHOR]

Hemorrhagic shock (HS) is the leading cause of death in trauma patients. Inflammation following HS can lead to cardiac damage. Pachymic acid (PA), a triterpenoid extracted from Poria cocos, has been found to possess various biological activities, including anti-inflammatory and anti-apoptotic properties. Our research aims to investigate the protective effects of PA against HS-induced heart damage and the underlying mechanisms involved. Male Sprague-Dawley rats were intraperitoneally injected with PA (7.5 or 15 mg/kg) daily for three days. Subsequently, we created a rat model of HS by drawing blood through a catheter inserted into the femoral artery followed by resuscitation. The results revealed that HS led to abnormalities in hemodynamics, serum cardiac enzyme levels, and cardiac structure, as well as induced cardiac apoptosis. However, pretreatment with PA effectively alleviated these effects. PA-pretreatment also suppressed mRNA and protein levels of interleukin (IL)-1 β , IL-6, and tumor necrosis factor α (TNF- α) in the heart tissues of HS rats. Additionally, PA-pretreatment reduced inflammatory cell infiltration and M1 macrophage polarization while exaggerating M2 polarization in HS rat hearts. The study observed a decreased proportion of the expression of of M1 macrophages (CD86 + ) and their marker (iNOS), along with an increased proportion of the expression of M2 macrophages (CD206 + ) and their marker (Arg-1). Notably, PA-pretreatment suppressed NF- κ B pathway activation via inhibiting NF- κ B p65 phosphorylation and its nuclear translocation. In conclusion, PA-pretreatment ameliorates HS-induced cardiac injury, potentially through its inhibition of the NF- κ B pathway. Therefore, PA treatment holds promise as a strategy for mitigating cardiac damage in HS. [ABSTRACT FROM AUTHOR]

Simple Summary: Previous epidemiological investigations suggested that Candida krusei (C. krusei) is one of the main pathogens of mycotic mastitis in dairy cows in Yinchuan, Ningxia, China. In this study, we examined the apoptotic signaling pathways in bovine mammary epithelial cells (BMECs) induced by the C. krusei yeast and hypha phases using a pathogen/host cell co-culture model. The results showed that the C. krusei yeast phase induced the apoptosis of BMECs through a mitochondrial pathway, while the apoptosis of BMECs induced by the C. krusei hypha phase was reached through a death ligand/receptor pathway. In addition, both the TLR2/ERK and JNK/ERK signaling pathways were involved in the regulation of C. krusei-induced BMEC apoptosis. These results provide a scientific basis for developing a comprehensive prevention and treatment approach for C. krusei mastitis in dairy cows. Infection with Candida spp. is a significant cause of bovine mastitis globally. We previously found that C. krusei was the main pathogen causing mycotic mastitis in dairy cows in Yinchuan, Ningxia, China. However, whether the infection of this pathogen could induce apoptosis in BMECs remained unclear. In this report, we explored the apoptosis and underlying mechanism of BMECs induced by C. krusei yeast and hypha phases using a pathogen/host cell co-culture model. Our results revealed that both the yeast and hypha phases of C. krusei could induce BMEC apoptosis; however, the yeast phase induced more cell apoptosis than the hypha phase, as assessed via electronic microscopy and flow cytometry assays. This finding was further corroborated via the measurement of the mitochondrial membrane potential (MMP) and the TUNEL test. Infection by both the yeast and hypha phases of C. krusei greatly induced the expression of proteins associated with cell death pathways and important components of toll-like receptor (TLR) signaling, including TLR2 and TLR4 receptors, as determined via a Western blotting assay. BMECs mainly underwent apoptosis after infection by the C. krusei yeast phase through a mitochondrial pathway. Meanwhile, BMEC apoptosis induced by the C. krusei hypha phase was regulated by a death ligand/receptor pathway. In addition, C. krusei-induced BMEC apoptosis was regulated by both the TLR2/ERK and JNK/ERK signaling pathways. These data suggest that the yeast phase and hypha phase of C. krusei induce BMEC apoptosis through distinct cell signaling pathways. This study represents a unique perspective on the molecular processes underlying BMEC apoptosis in response to C. krusei infection. [ABSTRACT FROM AUTHOR]

Chinese fir (Cunninghamia lanceolata (Lamb.) Hook.) stands as one of the pivotal afforestation tree species and timber resources in southern China. Nevertheless, the occurrence of seed abortion and a notably high proportion of astringent seeds significantly curtail the yield and quality of elite seeds, resulting in substantial economic losses. The development of astringent seeds is accompanied by significant physiological and biochemical alterations. Here, the first combined lipidomic and metabolomic analysis was performed to gain a comprehensive understanding of astringent seed traits. A total of 744 metabolites and 616 lipids were detected, of which 489 differential metabolites and 101 differential lipids were identified. In astringent seeds, most flavonoids and tannins, as well as proline and γ-aminobutyric acid, were more accumulated, along with a notable decrease in lipid unsaturation, indicating oxidative stress in the cells of astringent seeds. Conversely, numerous elemental metabolites were less accumulated, including amino acids and their derivatives, saccharides and alcohols, organic acids and nucleotides and their derivatives. Meanwhile, most lipid subclasses, mainly associated with energy storage (triglyceride and diglyceride) and cell membrane composition (phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine), also exhibited significant reductions. These results reflected a disruption in the cellular system or the occurrence of cell death, causing a reduction in viable cells within astringent seeds. Furthermore, only one lipid subclass, sphingosine phosphate (SoP), was more accumulated in astringent seeds. Additionally, lower accumulation of indole-3-acetic acid and more accumulation of salicylic acid (SA) were also identified in astringent seeds. Both SA and SoP were closely associated with the promotion of programmed cell death in astringent seeds. Collectively, our study revealed significant abnormal changes in phytohormones, lipids and various metabolites in astringent seeds, allowing us to propose a model for the development of astringent seeds in Chinese fir based on existing research and our findings. This work enriches our comprehension of astringent seeds and presents valuable bioindicators for the identification of astringent seeds. [ABSTRACT FROM AUTHOR]

Purpose-Immunotherapy has revolutionized cancer therapy, becoming the standard of care for various malignancy treatments. Human immunodeficiency virus (HIV) patients, however, are an underserved group with limited access to clinical trials and cancer therapy. This study was to evaluate the safety and efficacy of programmed cell death 1 (PD - 1) inhibitors in patients with advanced cancer and HIV/acquired immunodeficiency syndrome (AIDS). Methods and Materials-We performed a prospective, open-label, nonrandomized, phase 1 single center study. Patients with advanced cancer and HIV/AIDS received the treatment of PD - 1 inhibitors (camrelizumab, 200 mg, administered intravenously every 3 weeks), along with combination antiretroviral therapy (cART) for HIV. Results-Sixteen participants (12 men and 4 women; median age, 46.5 (29 - 78) years) were enrolled; 1 had non - Hodgkin lymphoma (NHL), and 15 had non - AIDS - defining cancers. Safety was observed over 130 cycles of treatment with camrelizumab. Most treatment-emergent adverse events at least possibly attributed to camrelizumab were grade 1 or 2, including reactive cutaneous capillary endothelial proliferation (RCCEP) (9 participants), hearing loss (1 participant), hypophysitis (1 participant). 3 participants experienced hemorrhage due to poor performance status. HIV was controlled in all participants. Best tumor responses included 3 complete response, 5 partial response, 2 stable disease, and 6 progressive disease. The 2 years progressionfree survival (PFS) was 67.0% (95% CI: -0.05, 0.00) and overall survival (OS) was 55.3% (95% CI: -0.05, 0.01) for the 16 patients who had received camrelizumab. Conclusions-This study demonstrates that camrelizumab treatment in patients with advanced cancers and HIV/AIDS was feasible and the clinical outcomes were acceptable. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) are important regulators on the onset and progression of rheumatoid arthritis (RA). Our purpose is to explore the role and underpin mechanism of circ_0000396 in RA progression. Methods: RA patients (n = 39) and healthy volunteers (n = 33) were recruited from the Affiliated Hospital of Shaanxi University of Chinese Medicine for the present work. Circ_0000396, microRNA-574-5p (miR-574-5p) and R-spondin 1 (RSPO1) RNA levels were analyzed by reverse transcription-quantitative polymerase chain reaction. Cell proliferation was analyzed by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, and 5-ethynyl-2′-deoxyuridine (EDU) assay. Cell apoptosis was assessed by flow cytometry. Protein expression levels of proliferating cell nuclear antigen (PCNA), Cyclin D1, Cyclin E1, BCL2-associated × protein (Bax), B-cell lymphoma-2 (Bcl2), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and RSPO1 were detected by western blot assay. Enzyme-linked immunosorbent assay (ELISA) was conducted to analyze the secretion of pro-inflammatory cytokines including IL-1β and TNF-α. The interaction between miR-574-5p and circ_0000396 or RSPO1 was confirmed by dual-luciferase reporter assay and RNA-pull down assay. Results: Circ_0000396 expression was notably down-regulated in RA patients compared with healthy controls. Circ_0000396 overexpression suppressed the proliferation and inflammatory response and triggered the apoptosis of RA synovial fibroblasts (RASFs), accompanied by decreases in PCNA, Cyclin D1, Cyclin E1, Bcl2, IL-1β and TNF-α protein expression and an increase in Bax protein expression. Circ_0000396 acted as a molecular sponge for miR-574-5p, and circ_0000396 overexpression-mediated protective effects on RASFs dysfunction were largely reversed by the introduction of miR-574-5p mimics. miR-574-5p interacted with the 3' untranslated region (3'UTR) of RSPO1, and miR-574-5p negatively regulated RSPO1 expression in RASFs. Circ_0000396 could up-regulate the expression of RSPO1 by sponging miR-574-5p in RASFs. RSPO1 interference largely overturned circ_0000396 overexpression-mediated effects in RASFs. Conclusion: Circ_0000396 restrained the proliferation and inflammation and induced the apoptosis of RASFs by mediating miR-574-5p/RSPO1 axis, which provided novel potential targets for RA treatment. [ABSTRACT FROM AUTHOR]

Total saponins from Trillium tschonoskii Maxim (TSTT), a bioactive component of local natural herbs in the Enshi area, China, have been demonstrated to have functions of restoring cognitive capacity and promoting axonal regeneration post-stroke, but the mechanism of this process remains unclear. The hippocampus is a critical tissue for controlling learning and memory capacity, and the sonic hedgehog (Shh) signaling pathway plays a major role in the patterning and synaptic plasticity of hippocampal neural circuits. Therefore, we aimed to investigate whether TSTT could restore learning and cognitive functions by modulating the Shh pathway in rats with post-stroke cognitive impairment (PSCI). The ischemia model was established by permanent middle cerebral artery occlusion (MCAO) in 100 Sprague-Dawley (SD) rats, and the model rats were administered using TSTT (100 mg/kg) or donepezil hydrochloride as the positive control (daily 0.45 mg/kg, DON) for 4 weeks after the operation. As assessed by the Morris water maze test, the cognitive function of PSCI rats was significantly improved upon TSTT treatment. Meanwhile, the cerebral infarct volume reduced with TSTT, as shown by HE and TTC staining, and the number of Nissl bodies and dendritic spine density were significantly increased, as shown by Nissl and Golgi staining. In addition, TSTT upregulated PSD-95, SYN, and GAP-43, and inhibited neuronal apoptosis, as evidenced by increased Bcl-2 levels along with decreased Bax and caspase-3 expression. TSTT could also significantly upregulate Shh, Ptch1, Smo, and Gli1 proteins, indicating the activation of the Shh signaling pathway. Therefore, TSTT can protect PSCI rats by inhibiting apoptosis and promoting neuronal synaptic remodeling. The Shh pathway is also involved. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the second leading cause of tumor-related deaths worldwide. Resistance of tumor cells to drug-induced apoptosis highlights the need for safe and effective antitumor alternatives. Erigeron breviscapus (Dengzhanxixin in China) injection (EBI), extracted from the natural herb Erigeron breviscapus (Vant.) Hand.-Mazz (EHM), has been widely used in clinical practice for cardiovascular diseases. Recent studies have suggested that EBI’s main active ingredients exhibit potential antitumor effects. This study aims to explore the anti-CRC effect of EBI and elucidate the underlying mechanism. The anti-CRC effect of EBI was evaluated in vitro using CCK-8, flow cytometry, and transwell analysis, and in vivo through a xenograft mice model. RNA sequencing was utilized to compare the differentially expressed genes, and the proposed mechanism was verified through in vitro and in vivo experiments. Our study demonstrates that EBI significantly inhibits the proliferation of three human CRC cell lines and effectively suppresses the migration and invasion of SW620 cells. Moreover, in the SW620 xenograft mice model, EBI markedly retards tumor growth and lung metastasis. RNA-seq analysis revealed that EBI might exert antitumor effects by inducing necroptosis of tumor cells. Additionally, EBI activates the RIPK3/MLKL signaling pathway, a classical pathway of necroptosis and greatly promotes the generation of intracellular ROS. Furthermore, the antitumor effect of EBI on SW620 is significantly alleviated after the pretreatment of GW806742X, the MLKL inhibitor. Our findings suggest that EBI is a safe and effective inducer of necroptosis for CRC treatment. Notably, necroptosis is a non-apoptotic programmed cell death pathway that can effectively circumvent resistance to apoptosis, which provides a novel approach for overcoming tumor drug resistance. [ABSTRACT FROM AUTHOR]

Simple Summary: Esophageal squamous cell cancer (ESCC) is an aggressive disease associated with a poor prognosis. The oxidative stress-related long non-coding RNAs (lncRNAs) play crucial roles in tumor prognosis. Our study identified seven oxidative stress-related DElncRNAs in the ESCC and build a prognostic risk model. The model exhibited an excellent ability for the prediction of overall survival (OS) and other clinicopathological traits using Kaplan–Meier (K-M) survival curves, receiver op-erating characteristic (ROC) curves, and the Wilcoxon test. Additionally, analysis of infiltrated immune cells and immune checkpoints indicated differences in immune status between the two risk groups. Finally, the in vitro experiments showed that PCDH9-AS1 overexpression inhibited proliferation ability and promoted apoptosis and oxidative stress levels in ESCC cells. In conclusion, the prognostic model constructed by oxidative stress-related DElncRNAs showed good performance in predicting the prognosis of patients with ESCC and was of great significance to guide the individualized treatment of these patients. Esophageal squamous cell cancer (ESCC) is an aggressive disease associated with a poor prognosis. Long non-coding RNAs (lncRNAs) and oxidative stress play crucial roles in tumor progression. We aimed to identify an oxidative stress-related lncRNA signature that could predict the prognosis in ESCC. In the GSE53625 dataset, we identified 332 differentially expressed lncRNAs (DElncRNAs) between ESCC and control samples, out of which 174 were oxidative stress-related DElncRNAs. Subsequently, seven oxidative stress-related DElncRNAs (CCR5AS, LINC01749, PCDH9-AS1, TMEM220-AS1, KCNMA1-AS1, SNHG1, LINC01672) were selected based on univariate and LASSO Cox to build a prognostic risk model, and their expression was detected by RT-qPCR. The model exhibited an excellent ability for the prediction of overall survival (OS) and other clinicopathological traits using Kaplan–Meier (K-M) survival curves, receiver operating characteristic (ROC) curves, and the Wilcoxon test. Additionally, analysis of infiltrated immune cells and immune checkpoints indicated differences in immune status between the two risk groups. Finally, the in vitro experiments showed that PCDH9-AS1 overexpression inhibited proliferation ability and promoted apoptosis and oxidative stress levels in ESCC cells. In conclusion, our study demonstrated that a novel oxidative stress-related DElncRNA prognostic model performed favorably in predicting ESCC patient prognosis and benefits personalized clinical applications. [ABSTRACT FROM AUTHOR]