BACKGROUND: Aberrant expression of apelin receptor (APLNR) has been found to be involved in various cancers\' development, however, its function in prostate cancer (PCa) remains unclear. The research aimed to investigate the role and potential mechanism of APLNR in PCa.
METHODS: The mRNA expression of APLNR was detected via qRT-PCR assay. PCa cell proliferation and apoptosis were determined through plate cloning and flow cytometry. In addition, the expression of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) was evaluated using western blot. DNA damage marker (γ-H2AX) was analyzed by immunofluorescence and western blot. GSEA analysis was performed for seeking enrichment pathways of APLNR in PCa, and the protein levels of PI3K, p-PI3K, AKT, p-AKT, mTOR, and p-mTOR were tested using western blot.
RESULTS: APLNR expression was up-regulated in PCa tissues and cells. Silencing APLNR enhanced the sensitivity of PCa cells to radiotherapy, which was manifested by inhibiting cell proliferation, promoting cell apoptosis, and promoting DNA damage. Next, silencing APLNR inhibited the PI3K/AKT/mTOR pathway. Specifically, 740Y-P (the PI3K/AKT/mTOR pathway activator) reversed the effects of silencing APLNR on PCa cell proliferation, apoptosis and DNA damage.
CONCLUSIONS: Silencing APLNR inhibited cell proliferation, promoted cell apoptosis, and enhanced the radiosensitivity of PCa cells, which was involved in the PI3K/AKT/mTOR signaling pathway. This study is conducive to the deeper understanding of PCa and further provides a new perspective for the treatment of PCa.

Coccidiosis is an important parasitic disease that has serious adverse effects on the global poultry industry. The mechanism by which the pathogenic factors of Eimeria tenella damage host cells is unknown. Some kinases from the rhoptry compartment can regulate apoptosis of host cells. This study focused on revealing the role and critical nodes of E. tenella rhoptry protein (EtROP) 38 in controlling the apoptosis of host cells via the P38 mitogen-activated protein kinase (MAPK) signaling pathway. The cells were treated with EtROP38 protein, siRNA p38MAPK, or both. The rate of infection, apoptosis, and the dynamic changes in the expression and activation of key factor genes of the P38MAPK signaling pathway in host cells infected with E. tenella were measured. The results showed that the addition of EtROP38 and/or knockdown of the host cells p38 gene reduced the apoptosis rate of cecal epithelial cells (CECS), decreased the mRNA expressions of p38, p53, c-myc, c-fos, and c-jun and increased the expression of p65, decreased the protein expressions of c-myc, c-fos, and c-jun, decreased the p38 protein phosphorylation level, and increased the p65 protein phosphorylation level in CECS. When E. tenella was inoculated for 4-96 h, the addition of Et ROP38 and/or host cell p38 knockdown both increased the infection rate of host cells, and this effect was more pronounced with the addition of EtROP38 with the host cell p38 knockdown. These observations indicate that E. tenella can inhibits the activation of the p38MAPK signaling pathway in host cells via EtROP38, which suppresses apoptosis in host cells.

Transforming growth factor-β (TGF-β) is a multifunctional cytokine that plays a vital role in regulating cell growth, differentiation and survival in various tissues. It participates in a variety of cellular processes, including cell apoptosis, cell migration and evasion, and plays a paradoxical role in tumor genesis and development. In the early stage of tumor, TGF-β inhibits the occurrence of tumor by inhibiting cell proliferation and regulating cell apoptosis. In the advanced stage of tumor, TGF-β promotes tumor development and affects prognosis by promoting cell survival and proliferation, cell migration and invasion, participates in immune escape, etc. In this article, we will review the paradoxical role of TGF-β on the occurrence and development of oral squamous cell carcinoma.

Phylloporia lonicerae is an annual fungus that specifically parasitizes living Lonicera plants, offering significant potential for developing new resource food and medicine. However, wild resources and mycelium production of this fungus is limited, and its anti-tumor active ingredients and mechanisms remain unclear, hampering the development of this fungus. Thus, we optimized the fermentation medium of P. lonicerae and studied the anti-tumor activity of its mycelium. The results indicated that the optimum fermentation medium consisted of 2% sucrose, 0.2% peptone, 0.1% KH2PO4, 0.05% MgSO4·7H2O, 0.16% Lonicera japonica petals, 0.18% P fungal elicitor, and 0.21% L. japonica stem. The biomass reached 7.82 ± 0.41 g/l after 15 days of cultivation in the optimized medium, a 142% increase compared with the potato dextrose broth medium, with a 64% reduction in cultivation time. The intracellular alcohol extract had a higher inhibitory effect on A549 and Eca-109 cells than the intracellular water extract, with half-maximal inhibitory concentration values of 2.42 and 2.92 mg/ml, respectively. Graded extraction of the alcohol extract yielded petroleum ether phase, chloroform phase, ethyl acetate phase, and n-butanol phase. Among them, the petroleum ether phase exhibited a better effect than the positive control, with a half-maximal inhibitory concentration of 113.3 μg/ml. Flow cytometry analysis indicated that petroleum ether components could induce apoptosis of Eca-109 cells, suggesting that this extracted component can be utilized as an anticancer agent in functional foods. This study offers valuable technical support and a theoretical foundation for promoting the comprehensive development and efficient utilization of P. lonicerae.

The inhibitory properties and underlying mechanism of chlorine dioxide (ClO2) fumigation on the pathogen Ceratocystis fimbriata (C. fimbriata) and resultant sweetpotato black rot were investigated in vitro and in vivo. Results revealed that the ClO2 fumigation effectively inhibited fungal growth and induced obvious morphological variation of C. fimbriata mycelia. Furthermore, the mycelial membrane suffered damage, as evidenced by a significant increase in malondialdehyde content and the leakage of protein and nucleic acid from mycelia cells, accompanied by a marked decrease in ergosterol content. Additionally, ClO2 fumigation caused spores cell membrane damage, a notable decrease in spore viability, and induced cell apoptosis as indicated by reductions in spore germination rate, two fluorescence staining observations, and flow cytometry analysis. Moreover, the decay diameter of sweetpotato black rot lesions decreased significantly after ClO2 fumigation, and the growth of C. fimbriata was also inhibited. These findings present a novel and effective technology for inhibiting the progression of sweetpotato black rot.

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UNASSIGNED: To elucidate the role of circVRK1 and its interaction with miR-4428 in regulating proliferation and apoptosis in acute lymphoblastic leukemia (ALL) cells.
UNASSIGNED: KOCL44 ALL cells were cultured in vitro, and experimental groups included pcDNA, pcDNA-circVRK1, anti-miR-NC, anti-miR-4428, si-NC, si-circVRK1, pcDNA-circVRK1+miR-NC, and pcDNA-circVRK1+miR-4428. The expression levels of circVRK1 and miR-4428 were detected using qRT-PCR. CCK-8 assays and flow cytometry were used to assess cell proliferation and apoptosis, respectively. The dual luciferase reporter assays were employed to investigate the interaction between circVRK1 and miR-4428, with groups categorized as WT-circVRK1+miR-NC, WT-circVRK1+miR-4428, MUT-circVRK1+miR-NC, and MUT-circVRK1+ miR-4428. Western blotting was utilized to detect the expression levels of Ki-67, cleaved caspase-3, and cleaved caspase-9 proteins.
UNASSIGNED: Compared to the pcDNA group, circVRK1 expression was up-regulated in the pcDNA-circVRK1 group (P<0.05). Compared to transfection with pcDNA or anti-miR-NC, transfection with pcDNA-circVRK1 or anti-miR-4428 led to decreased cell viability and Ki-67 protein levels in KOCL44 cells (P<0.05), and increased apoptosis rates and levels of cleaved caspase-3 and cleaved caspase-9 (P<0.05). circVRK1 was found to negatively regulate miR-4428 expression, with this effect observed only in the WT-circVRK1 group. miR-4428 levels were lower in the pcDNA-circVRK1 group compared to the pcDNA group (P<0.05) and higher in the si-circVRK1 group compared to the si-NC group (P<0.05). Co-transfection with pcDNA-circVRK1+miR-4428 resulted in increased cell viability (P<0.05) and Ki-67 expression (P<0.05), and decreased apoptosis rates and levels of cleaved caspase-3 and cleaved caspase-9 (P<0.05) compared to co-transfection with pcDNA-circVRK1+miR-NC.
UNASSIGNED: Overexpression of circVRK1 reduces the proliferation ability of acute ALL cells and induces cell apoptosis by downregulating miR-4428 expression.

Fucoxanthin (FX), a non-provitamin-A carotenoid, is a well-known major xanthophyll contained in edible brown algae. The nanoencapsulation of FX was motivated due to its multiple activities. Here, nano-encapsulated-FX (nano-FX) was prepared according to our early method by using whey protein and flaxseed gum as the biomacromolecule carrier material, then in vivo antitumor effect and mechanism of nano-FX on xenograft mice were investigated. Thirty 4-week-old male BALB/c nude mice were fed adaptively for 7 days to establish xenograft tumor model with Huh-7 cells. The tumor-bearing mice consumed nano-FX (50, 25, and 12.5 mg kg-1) and doxorubicin hydrochloride (DOX, 1 mg kg-1) or did not consume (Control) for 21 days, n = 6. The tumor inhibition rates of nano-FX were as high as 54.67 ± 1.04 %. Nano-FX intervention promoted apoptosis and induced hyperchromatic pyknosis and focal necrosis in tumor tissue by down-regulating the expression of p-JNK, p-ERK, PI3Kp85α, p-AKT, p-p38MAPK, Bcl-2, CyclinD1 and Ki-67, while up-regulating the expression of cleaved caspase-3 and Bax. Nano-FX inhibited tumor growth and protected liver function of tumor bearing mice in a dose-dependent manner, up-regulate the level of apoptosis-related proteins, inhibit the MAPK-PI3K/Akt pathways, and promote tumor cell apoptosis.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic ovulation dysfunction and overproduction of androgens. Women with PCOS are commonly accompanied by insulin resistance (IR), which can impair insulin sensitivity and elevate blood glucose levels. IR promotes ovarian cysts, ovulatory dysfunction, and menstrual irregularities in women patients, leading to the pathogenesis of PCOS. Secreted frizzled-related protein 4 (SFRP4), a secreted glycoprotein, exhibits significantly elevated expression levels in obese individuals with IR and PCOS. Whereas, whether it plays a role in regulating IR-induced PCOS still has yet to be understood. In this study, we respectively established in vitro IR-induced hyperandrogenism in human ovarian granular cells and in vivo IR-induced PCOS models in mice to investigate the action mechanisms of SFRP4 in modulating IR-induced PCOS. Here, we revealed that SFRP4 expression levels in both mRNA and protein were remarkably upregulated in the IR-induced hyperandrogenism with elevated testosterone in the human ovarian granulosa cell line KGN. Under normal conditions without hyperandrogenism, overexpressing SFRP4 triggered the remarkable elevation of testosterone along with the increased nuclear translocation of β-catenin, cell apoptosis and proinflammatory cytokine IL-6. Furthermore, we found that phytopharmaceutical disruption of SFRP4 by genistein ameliorated IR-induced increase in testosterone in ovarian granular cells, and IR-induced PCOS in high-fat diet obese mice. Our study reveals that SFRP4 contributes to IR-induced PCOS by triggering ovarian granulosa cell hyperandrogenism and apoptosis through the nuclear β-catenin/IL-6 signaling axis. Elucidating the role of SFRP4 in PCOS may provide a novel therapeutic strategy for IR-related PCOS therapy.