CircCRIM1/microRNA-141-3p/thioredoxin-binding protein axis mediates neuronal apoptosis after cerebral ischemia-reperfusion.

Numerous studies have indicated enrichment of circular RNA (circRNA) in the brain takes on a momentous role in cerebral ischemia-reperfusion (CIR) injury. A recent study discovered a novel circCRIM1, was highly expressed in the middle cerebral artery occlusion-reperfusion (MCAO/R) model. Nevertheless, its specific biological function remained unknown. The study was to explore circCRIM1 in CIR-induced neuronal apoptosis. As measured, circCRIM1 and TXNIP were up-regulated, while miR-141-3p was down-regulated in MCAO/R mouse model and OGD/R SH-SY5Y cells. Depleting circCRIM1 reduced the number of apoptotic neurons in MCAO/R rats, increased the number of Nissl bodies, prevented reactive oxygen species production and oxidative stress imbalance in brain tissues, repressed cleaved caspase-3, Bax, and Cyto C protein levels and increased Bcl-2 levels. Overexpression of circCRIM1 further repressed neuronal activity and accelerated apoptosis in OGD/R model, disrupted redox balance. Depleting circCRIM1 had the opposite effect in OGD/R model. Knocking down miR-141-3p or TXNIP weakened the effects of knocking down circCRIM1 or overexpressing circCRIM1, separately. Mechanistically, circCRIM1 exerted an active role in CIR injury via miR-141-3p to mediate TXNIP. All in all, the circCRIM1/miR-141-3p/TXNIP axis might be a latent therapeutic target for CIR injury.

Analysis of Metabolites and Metabolic Pathways of Three Chinese Jujube Cultivar.

Most studies on metabolites in jujube fruits focus on specific types of metabolites, but there are only a few comprehensive reports on the metabolites in jujube fruits. In order to understand the variance of metabolites in fruits of different jujube varieties. The objective of this study was to explore the metabolic components of jujube fruit by comparing three cultivars, namely Linyi LiZao (LZ), Jiaocheng SuantianZao (STZ), and Xianxian Muzao (MZ). The metabolites present in the fruits of these three cultivars were evaluated and compared. The results revealed the detection of 1059 metabolites across the three jujube varieties, with each cultivar exhibiting distinct metabolic characteristics. Notably, MZ exhibited a higher abundance of six metabolite classes, namely amino acids and derivatives, flavonoids, lipids, organic acids, phenolic acids, and terpenoids, compared to LZ. Conversely, LZ exhibited higher concentrations of alkaloids, lignans, coumarins, nucleotides, and their derivatives compared to the other two cultivars. In terms of STZ, its content of amino acids and derivatives, lignans and coumarins, organic acids, and phenolic acids was largely similar to that of LZ. However, the content of alkaloids, nucleotides, and their derivatives, and terpenoids was significantly higher in STZ compared to LZ. Additionally, STZ exhibited lower levels of flavonoids and lipids compared to LZ. Moreover, MZ was found to be less nutritionally rich than STZ, except for lignans and coumarins, as it displayed lower levels of all the metabolites. KEGG pathway enrichment analysis revealed six significantly different metabolic pathways (p < 0.05) between LZ and MZ, including arginine and proline metabolism, sphingolipid metabolism, flavonoid biosynthesis, glutathione metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism. The metabolites in STZ and MZ exhibited three significantly different pathways (p < 0.05), primarily associated with flavonoid biosynthesis, arginine and proline metabolism, and sphingolipid metabolism. The significantly differential metabolites between LZ and STZ were observed in the phenylpropionic acid biosynthesis pathway and the ubiquinone and other terpenoid-quinone biosynthesis pathways. LZ showed a closer relationship with STZ than with MZ. STZ and LZ exhibited higher medicinal values, while LZ had lower acidity and MZ displayed better antioxidant activity. This study presents the first thorough analysis of metabolites in LZ, STZ, and MZ cultivars, which can serve as a theoretical basis for quality analysis, functional research, and classification processing of jujube fruit.

Effects of four disease-controlling agents (chlorothalonil, CuCl2, harpin, and melatonin) on postharvest jujube fruit quality.

Postharvest senescence and disease development can reduce the nutritional value of fresh jujube fruit. Herein, four different disease-controlling agents (chlorothalonil, CuCl2, harpin and melatonin) were separately applied to fresh jujube fruit, and all improved postharvest quality (evaluated by disease severity, antioxidant accumulation and senescence) relative to controls. Disease severity was drastically inhibited by these agents, in the order chlorothalonil > CuCl2 > harpin > melatonin. However, chlorothalonil residues were detected even after storage for 4 weeks. These agents increased the activities of defense enzymes including phenylalanine ammonia-lyase, polyphenol oxidase, glutathione reductase and glutathione S-transferase, as well as accumulation of antioxidant compounds such as ascorbic acid, glutathione, flavonoids and phenolics, in postharvest jujube fruit. The enhanced antioxidant content and antioxidant capacity (evaluated by Fe3+ reducing power) was ordered melatonin > harpin > CuCl2 > chlorothalonil. All four agents significantly delayed senescence (evaluated by weight loss, respiration rate and firmness), with the effect ordered CuCl2 > melatonin > harpin > chlorothalonil. Moreover, treatment with CuCl2 also increased copper accumulation ~ threefold in postharvest jujube fruit. Among the four agents, postharvest treatment with CuCl2 could be considered most appropriate for improving postharvest jujube fruit quality under low temperature conditions without sterilization.

Outcomes After a Single Ovarian Stimulation Cycle in Women of Advanced Reproductive Age: A Retrospective Analysis.

OBJECTIVES: Previous studies showed that age is the most important factor that determines the outcome after embryo transfer (ET), with either in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), regardless whether fresh or frozen cycles. The average cumulative live birth rate (CLBR) following a single ovarian stimulation cycle in women of advanced reproductive age (≥38 years of age) has been reported to be 22.6-34.1%. The purpose of this study is to compare the CLBR after a single ovarian stimulation cycle in women of different advanced reproductive age bracket (38/39, 40/41, 42/43 years of age or older), and to explore the factors (e.g., age, type of infertility, body mass index (BMI), ovarian stimulation protocols) associated with CLBR. METHODS: This retrospective analysis included all women of advanced reproductive age (38 years or older) undergoing IVF or ICSI at authors' institute during a period from January 1, 2016 to December 31, 2018. The study protocol was approved by the Ethics Committee of the Second Hospital of Hebei Medical University (No. 2021-P045). Subjects with underlying diseases were excluded from analysis. The last follow-up was conducted in December 2020, with minimal 2-year follow-up. RESULTS: The final analysis included 826 women (40.00 ± 2.10 years of age at the time of ovarian stimulation; n = 633 and 193 for IVF-ET and ICSI-ET, respectively). The number of women in each age bracket was: 424 for 38/39 y, 226 for 40/41 y, 118 for 42/43 y, and 58 for ≥44 y. The number of transferable embryos was 2 (interquartile range: 2,4) for 38/39 y, 2 (2,3) for 40/41 y, 2 (2,3) for 42/43 y, and 2 (1.75,3) for ≥44 y. The rate of fresh embryo transfer was comparable (62.03-72.58%) among the 4 age brackets. The average CLBR following a single cycle was 26.27% in the overall study population, 32.31% for 38/39 y, 26.99% for 40/41 y, 14.4% for 42/43 y, and 3.44% for ≥44 y (P <0.001). In multivariate regression, CLBR was independently associated with younger age (OR for each year: 1.538, 95%CI: 1.193, 1.984) and higher number of transferable embryos (OR for each embryo: 1.495, 95%CI: 1.297, 1.722). CLBR differed significantly in the 38/39 group (P = 0.014), with higher rate in women receiving the Gonadotropin-releasing hormone agonist (GnRH-a) long or GnRH-a ultra-long protocols. CONCLUSIONS: Forty-two years of age seemed to be a critical cutoff to achieve reasonable level of CLBR after a single ovarian stimulation cycle in women of advanced reproductive age.

Depleting SOX2 improves ischemic stroke via lncRNA PVT1/microRNA-24-3p/STAT3 axis.

OBJECTIVES: Studies have widely explored in the filed of ischemic stroke (IS) with their focus on transcription factors. However, few studies have pivoted on sex determining region Y-box 2 (SOX2) in IS. Thus, this study is launched to figure out the mechanisms of SOX2 in IS. METHODS: Rat middle cerebral artery occlusion (MCAO) was established as a stroke model. MCAO rats were injected with depleted SOX2 or long non-coding RNA plasmacytoma variant translocation 1 (PVT1) to explore their roles in neurological deficits, cerebral water content, neuron survival, apoptosis and oxidative stress. The relationship among SOX2, PVT1, microRNA (miR)-24-3p and signal transducer and activator of transcription 3 (STAT3) was verified by a series of experiments. RESULTS: SOX2, PVT1 and STAT3 were highly expressed while miR-24-3p was poorly expressed in cerebral cortex tissues of MCAO rats. Depleted SOX2 or PVT1 alleviated brain injury in MCAO rats as reflected by neuronal apoptosis and oxidative stress restriction, brain water content reduction, and neurological deficit and neuron survival improvements. Overexpression of PVT1 functioned oppositely. Restored miR-24-3p abolished PVT1 overexpression-induced brain injury in MCAO rats. SOX2 directly promoted PVT1 expression and further increased STAT3 by sponging miR-24-3p. CONCLUSION: This study presents that depleting SOX2 improves IS via PVT1/miR-24-3p/STAT3 axis which may broaden our knowledge about the mechanisms of SOX2/PVT1/miR-24-3p/STAT3 axis and provide a reference of therapy for IS.

Glycine Improves Ischemic Stroke Through miR-19a-3p/AMPK/GSK-3ß/HO-1 Pathway.

PURPOSE: To explore the molecular mechanism of glycine in improving ischemic stroke. PATIENTS AND METHODS: The serum samples of patients with ischemic stroke and healthy people were compared. The ischemic stroke model of PC12 cells was established by oxygen-glucose deprivation (OGD). qPCR quantified miR-19a-3p and AMPK mRNA, and protein expression was detected by Western blot. MTT was used to detect cell activity. Flow cytometry was used to detect cells. Glucose metabolism kit was used to detect glucose intake and formation amount of lactic acid. RESULTS: Compared with the control group, OGD group (OGDG) showed lower cell activity and increased cell apoptosis. TNF-α, IL-1ßI, L-6, Caspase 3, Caspase 9 and Bax were up-regulated, and Glut1, HK2, LDHA, PDK1, PKM2 and Bcl2 were down-regulated. At the same time, glucose intake, formation amount of lactic acid and cell apoptosis rate were reduced, and AMPK/GSK-3ß/HO-1 pathway activity was down-regulated. Glycine could counteract the above phenomena in OGDG. miR-19a-3p and AMPK decreased and increased, respectively, during glycine therapy. AMPK was the target gene of miR-19a-3p. Rescue experiments demonstrated that glycine improved cell apoptosis, inflammatory response and glucose metabolism disorder of ischemic stroke through miR-19a-3p/AMPK/GSK-3ß/HO-1 pathway. CONCLUSION: Glycine improves ischemic stroke through miR-19a-3p/AMPK/GSK-3ß/HO-1 pathway.

Oncogenic USP22 supports gastric cancer growth and metastasis by activating c-Myc/NAMPT/SIRT1-dependent FOXO1 and YAP signaling.

In this study, we investigated the role of ubiquitin-specific protease 22 (USP22) in the growth and progression of gastric cancer (GC). USP22 mRNA and protein levels were significantly higher in GC tissue samples and GC cell lines than in adjacent noncancerous tissue samples and a normal gastric mucosal epithelial cell line (GES1), respectively. USP22 knockdown significantly decreased in vitro survival, proliferation, migration, and invasiveness of GC cells compared with the controls. Western blot analysis of control and USP22-silenced GC cells showed that USP22 modulates the c-Myc/NAMPT/SIRT1-dependent FOXO1 and YAP signaling pathways. Subcutanenous injection of USP22-silenced GC cells into SCID mice generated significantly smaller xenograft tumors than did control cells. Moreover, USP22-silenced GC cells showed less lung metastasis than the controls following tail vein injection in SCID mice. In addition, high USP22 expression correlated positively with tumor size, advanced stage and metastasis, and correlated negatively with tumor differentiation and prognosis in GC patients. These results show that USP22 regulates growth and progression of GC via the c-Myc/NAMPT/SIRT1-dependent FOXO1 and YAP signaling pathways.

Inhibition of autophagy by hydroxychloroquine enhances antioxidant nutrients and delays postharvest fruit senescence of Ziziphus jujuba.

Autophagy, a mechanism of recycling intracellular constituents, favors plant growth, especially under nutrient starvation. However, autophagy's role in regulating postharvest fruit senescence is unclear. Here, effects of the autophagy inhibitor hydroxychloroquine (HCQ) and activator LiCl on postharvest jujube fruit senescence were investigated. HCQ significantly reduced weight loss and decay incidence, and enhanced firmness compared with those of the control. LiCl had the opposite effects. Protein oxidation and H2O2 increased significantly in LiCl-treated compared with HCQ-treated fruit. The contents of vitamin C, total thiol, and phenolics, and total antioxidant capacity and DPPH-radical scavenging capacity, followed the order: HCQ > control > LiCl. The HCQ-mediated reduction in fruit respiration was significantly enhanced by ATP and partly reversed by 2,4-dinitrophenol, a mitochondrial uncoupler. Thus, jujube fruit senescence may be regulated by autophagy and the antioxidant capacity. A mechanism of autophagy-mediated postharvest fruit senescence involving mitochondrial biogenesis and respiration was proposed.

Transcriptome analysis of genes involved in defense against alkaline stress in roots of wild jujube (Ziziphus acidojujuba).

Wild jujube (Ziziphus acidojujuba Mill.) is highly tolerant to alkaline, saline and drought stress; however, no studies have performed transcriptome profiling to study the response of wild jujube to these and other abiotic stresses. In this study, we examined the tolerance of wild jujube to NaHCO3-NaOH solution and analyzed gene expression profiles in response to alkaline stress. Physiological experiments revealed that H2O2 content in leaves increased significantly and root activity decreased quickly during alkaline of pH 9.5 treatment. For transcriptome analysis, wild jujube plants grown hydroponically were treated with NaHCO3-NaOH solution for 0, 1, and 12 h and six transcriptomes from roots were built. In total, 32,758 genes were generated, and 3,604 differentially expressed genes (DEGs) were identified. After 1 h, 853 genes showed significantly different expression between control and treated plants; after 12 h, expression of 2,856 genes was significantly different. The expression pattern of nine genes was validated by quantitative real-time PCR. After gene annotation and gene ontology enrichment analysis, the genes encoding transcriptional factors, serine/threonine-protein kinases, heat shock proteins, cysteine-like kinases, calmodulin-like proteins, and reactive oxygen species (ROS) scavengers were found to be closely involved in alkaline stress response. These results will provide useful insights for elucidating the mechanisms underlying alkaline tolerance in wild jujube.

Biological effects and clinical characteristics of microRNA-106a in human colorectal cancer.

MicroRNAs serve important roles in various diseases, particularly cancer. microRNA-106a (miR-106a) exhibits abnormal expression and oncogenic activity in carcinogenesis. The clinical significance of the abnormal expression of miR-106a in colorectal cancer is poorly understood. In the present study, miR-106a expression from colorectal cancer tissues was quantified using the reverse transcription-quantitative polymerase chain reaction. The overexpression or knockdown of miR-106a was performed by transfection with microRNA mimic or inhibitor in human colorectal carcinoma HCT116 cells. The overexpression of miR-106a promoted viability and inhibited apoptosis in colorectal cancer cells. The association between miR-106a expression and clinicopathological factors was analyzed, and it was identified that miR-106a exhibited significantly increased expression in adenocarcinoma tissues compared with in mucinous carcinoma tissues, and the expression of miR-106a was identified to be associated with the depth of invasion and differentiation. The expression of miR-106a in plasma was also determined and it was identified that increased expression of miR-106a, as a characteristic of patients with colorectal cancer, may be distinguished from that of other patients by digitization of the areas under the receiver operating characteristic curves. These data suggested that miR-106a is a potential biomarker in the diagnosis of colorectal carcinoma. However, the underlying molecular mechanism of miR-106a-promoted viability and inhibition of apoptosis requires further investigation.

Iron uptake, translocation and regulation in rice.

Iron is essential for growth and development of rice, which is able to take up Fe3+-phytosiderophore, Fe2+-nicotianamine and free Fe2+. Researchers have uncovered key molecular components including transporters, enzymes, and chelators involved in iron uptake and translocation, as well as factors regulating the expression of these genes in rice. Manipulation of these molecular components has produced transgenic rice with enhanced tolerance to alkaline stress on calcareous soils with low-Fe availability due to high soil pH. In this review, we mainly summarize the molecular mechanisms of iron uptake, translocation, and regulation in rice, and discuss some perspectives of this field.