Search

Long noncoding RNA nuclear enriched abundant transcript 1 (NEAT1) has been reported to be involved in depression. This study aims to investigate the mechanism of NEAT1/microRNA (miR)-320-3p/Corticotropin-releasing hormone receptor 1 (CRHR1) axis in depressed rats. Rats with depression-like behaviors were prepared by exposing the rats to chronic unpredictable mild stress. Behavioral functions, pathological damage, neuronal apoptosis and monoamine neurotransmitter were examined in depressed rats . Primary hippocampal neurons were injured through simulation with corticosterone(CORT). Cell viability and apoptosis were measured in CORT-Induced hippocampal neurons. The binding relationship between NEAT1 and miR-320-3p and the targeting relationship between miR-320-3p and CRHR1 were detected. Elevated NEAT1, CRHR1 and reduced miR-320-3p exhibited in depressed rats and CORT-treated hippocampal neurons, NEAT1 bound to miR-320-3p to target CRHR1. Silencing NEAT1 or elevating miR-320-3p improved behavioral functions, attenuated pathological damage and apoptosis in the hippocampus, and increased monoamine neurotransmitter in depressed rats. Repression of NEAT1 or promotion of miR-320-3p enhanced viability and suppressed apoptosis of CORT-treated hippocampal neurons. The study highlights that NEAT1 competitively binds to miR-320-3p to up-regulate CRHR1 expression, thereby promoting hippocampal damage of depressed rats., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Parkinson's disease (PD), a common multifactorial neurodegenerative disease, is characterized by irreversible loss of dopaminergic neurons in the substantia nigra. In‑depth study of the pathogenesis of PD is of great importance. High‑mobility group AT‑hook 2 (HMGA2) has been proposed to be implicated with neuronal differentiation and impairment of cognitive function. However, whether HMGA2 plays a role in PD is rarely explored. In the present study, N‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine (MPTP)‑treated PD mice models and N‑methyl‑4‑ phenylpyridinium (MPP + )‑treated SH‑SY5Y cell models were established. Reverse transcription‑quantitative PCR showed that HMGA2 displayed low levels in brain tissues of MPTP‑treated mice and MPP + ‑treated SH‑SY5Y cells. Moreover, HMGA2 overexpression suppressed SH‑SY5Y cell apoptosis. Additionally, let‑7b‑5p bound with HMGA2 3' untranslated region (UTR), and its expression was negatively correlated with HMGA2 level. Moreover, let‑7b‑5p presented high levels in brain tissues of PD mice and MPP+‑treated SH‑SY5Y cells, and knockdown of let‑7b‑5p inhibited SH‑SY5Y cell apoptosis. Rescue assays illustrated that HMGA2 neutralized the promotive effects of let‑7b‑5p mimics on SH‑SY5Y cell apoptosis. In conclusion, the present study demonstrated that let‑7b‑5p contributes to cell apoptosis in PD by targeting HMGA2, which offers a potential theoretical basis for the study of effective therapy in PD.

The human cytomegalovirus (HCMV) encodes ≥26 microRNAs (miRNAs). These miRNAs are utilized by HCMV to regulate its own genes in addition to the genes of the host cell, during infection. The present study first identified p21‑activated kinase 2 (PAK2) as a target of hcmv‑miR‑US4‑5p, via hybrid polymerase chain reaction, which was further verified using a luciferase reporter assay. The protein expression level of PAK2, detected via western blotting, was demonstrated to be directly downregulated by overexpression of hcmv‑miR‑US4‑5p in HEK293, HELF and THP‑1 cells. Furthermore, it was demonstrated that the PAK2 protein level in naturally infected HELF cells was gradually decreased at 24, 48 and 72 h post infection with increased hcmv‑miR‑US4‑5p expression. The use of PAK2‑specific small interfering RNA and an inhibitor for hcmv‑miR‑US4‑5p, demonstrated that the promotion of apoptosis by hcmv‑miR‑US4‑5p in these cells was specifically mediated via inhibition of PAK2 expression. These results indicated that hcmv‑miR‑US4‑5p may exhibit this activity during natural HCMV infection, in order to establish a balance between the host cell and virus.

Objective: To investigate the effect of the traditional Chinese medicine compound Yisui Lixue decoction on apoptosis of marrow cells in rats with myelodysplastic syndrome (MDS) induced by dimethyl benzanthracene (DMBA). 
 Methods: The rats with MDS induced by the chemical mutagens DMBA were divided into 5 groups (12 rats in each group): a control group, a model+PBS group, a model+compound Zaofan pill group, a model+low dose of Yisui Lixue decoction group and a model+high dose of Yisui Lixue decoction group. After DMBA treatment for 14 days, rats were treated with different drugs for 1 month and executed on the 31 day. The peripheral blood cells, expressions of B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax), apoptosis of bone marrow cells were measured.
 Results: The counts of peripheral leukocyte, erythrocyte, hemoglobin and platelet in the model+PBS group were significantly decreased compared with those in the control group (P<0.01), while the peripheral hemograms of the treatment groups were improved significantly compared with those in the model+PBS group (P<0.05 or P<0.01), especially in the model+high dose group (P<0.01). In the model+PBS group, the expressions of Bax and Bcl-2 was significantly increased (P<0.01) or decreased (P<0.01), respectively, which were reversed by treatment of Yisui Lixue decoction (P<0.05 or P<0.01), especially in the model+high dose group (P<0.01). Compared with control group, the total apoptosis rate, earlier apoptosis and later apoptosis rate of bone marrow cells in the model+PBS group were increased (P<0.01), which were blocked by treatment of Yisui Lixue decoction (P<0.05 or P<0.01), and the model+high dose group was better than the model+low dose group. 
 Conclusion: The traditional Chinese medicine compound Yisui Lixue decoction can improve peripheral hemogram, decrease the expression of Bax, increase the expression of Bcl-2, and reduce the apoptosis of bone marrow cells.

Human cytomegalovirus (HCMV) encodes at least 26 microRNAs (miRNA). These miRNAs are utilized by HCMV to regulate its own genes as well as the genes of the host cell during infection. It has been reported that a cellular gene, solute carrier family 25, member 6 (SLC25A6), which is also designated adenine nucleotide translocator 3 (ANT3), was identified as a candidate target of hcmv-miR-UL36-5p by hybrid PCR. In this study, ANT3 was further demonstrated to be a direct target of hcmv-miR-UL36-5p by luciferase reporter assays. The expression level of ANT3 protein was confirmed, by western blotting, to be directly downregulated by overexpression of hcmv-miR-UL36-5p in HEK293 cells, U373 cells and HELF cells. Moreover, HCMV-infected cells showed a decrease in the ANT3 protein level. Using ANT3-specific small interfering RNA (siRNA) and an inhibitor for hcmv-miR-UL36-5p, it was shown that inhibition of apoptosis by hcmv-miR-UL36-5p in these cells specifically occurred via inhibition of ANT3 expression. These results imply that hcmv-miR-UL36-5 may play the same role during actual HCMV infection in order to establish a balance between the host cell and the virus.

Ischemic stroke is a major cerebrovascular disease resulting from a transient or permanent local reduction of cerebral blood flow. Angiogenesis plays an important role in cerebral microvascular repair after ischemic stroke. This study aimed at investigating the effect of NF-E2-related factor 2 (Nrf2) on the angiogenesis of mouse cerebral microvascular endothelial bEnd.3 cells in a hypoxic environment. We found that Nrf2 expression was temporarily increased in hypoxia-induced bEnd.3 cells. Knockdown of Nrf2 inhibited the proliferation, migration, as well as tube formation in hypoxia-induced bEnd.3 cells. Meanwhile, vascular endothelial growth factor and PI3K/Akt signaling pathways were identified to be regulated by Nrf2 in hypoxia-induced bEnd.3 cells. It was found that silencing of Nrf2 downregulated the expression levels of NAD(P)H:quinine oxidoreductase-1, vascular endothelial growth factor, p-Akt, and heme oxygenase-1 in hypoxia-induced bEnd.3 cells. Data suggested that hypoxia induced the transient increase of Nrf2, which plays a key role in the angiogenesis of cerebral microangiogenesis, and that Nrf2 regulates the proliferation, migration, as well as tube formation likely through PI3K/Akt signaling pathway in hypoxia-induced bEnd.3 cells. Our study provides proof of concept for the modulation of Nrf2, so as to tilt the balance toward angiogenesis, representing a therapeutic strategy for hypoxia or ischemia disorders such as stroke. [ABSTRACT FROM AUTHOR]