Porcine Granulosa-Cell-Derived Exosomes Enhance Oocyte Development: An In Vitro Study.

Recent studies have established that exosomes (EXs) derived from follicular fluid (FF) can promote oocyte development. However, the specific sources of these EXs and their regulatory mechanisms remain elusive. It is universally acknowledged that oocyte development requires signal communication between granulosa cells (GCs) and oocytes. However, the role of GC-secreted EXs and their functions are poorly understood. This study aimed to investigate the role of porcine granulosa-cell-derived exosomes (GC-EXs) in oocyte development. In this study, we constructed an in vitro model of porcine GCs and collected and identified GC-EXs. We confirmed that porcine GCs can secrete EXs and investigated the role of GC-EXs in regulating oocyte development by supplementing them to cumulus-oocyte complexes (COCs) cultured in vitro. Specifically, GC-EXs increase the cumulus expansion index (CEI), promote the expansion of the cumulus, alleviate reactive oxygen species (ROS), and increase mitochondrial membrane potential (MMP), resulting in improved oocyte development. Additionally, we conducted small RNA sequencing of GC-EXs and hypothesized that miR-148a-3p, the highest-expressed microRNA (miRNA), may be the key miRNA. Our study determined that transfection of miR-148a-3p mimics exerts effects comparable to the addition of EXs. Meanwhile, bioinformatics prediction, dual luciferase reporter gene assay, and RT-qPCR identified DOCK6 as the target gene of miR-148a-3p. In summary, our results demonstrated that GC-EXs may improve oocyte antioxidant capacity and promote oocyte development through miR-148a-3p by targeting DOCK6.

Bromodomain-containing protein 4 inhibition improves the efficacy of cisplatin and radiotherapy in oral squamous cell carcinoma by suppressing programmed cell death-ligand 1 expression.

The bromodomain-containing protein 4 (BRD4) is highly expressed in oral squamous cell carcinoma (OSCC) and plays a crucial role in tumour progression. However, the impact of BRD4 on the efficacy of chemotherapy and radiotherapy by regulating the expression of programmed cell death-ligand 1 (PD-L1) in OSCC remains unclear. In this study, we found that the BRD4 inhibitor JQ1 effectively enhanced the inhibitory effects of cisplatin and radiotherapy on cell proliferation and promoted the apoptosis of OSCC cells by cisplatin and radiotherapy. Furthermore, treatment with JQ1 reversed the increase of the expression of PD-L1 by cisplatin and radiotherapy, whereas the overexpression of PD-L1 partially countered the beneficial effects of JQ1 on the anticancer efficacy of cisplatin and radiotherapy. These results demonstrate that the inhibition of BRD4 improves the anticancer effect of chemotherapy and radiotherapy by suppressing the expression of PD-L1 in OSCC, suggesting that targeting BRD4 could be a promising therapeutic approach for chemo/radioresistant OSCC.

Deciphering the Mechanism of Bushen Huoxue Decotion on Decidualization by Intervening Autophagy via AMPK/mTOR/ULK1: A Novel Discovery for URSA Treatment.

Impaired decidualization was recognized as one of the crucial pathomechanisms accounting for unexplained recurrent spontaneous abortion (URSA). Currently, the exact molecular mechanism and targeted clinical decision are still in exploration. Bushen Huoxue decoction (BSHXD) has previously been proved effective in treating URSA, but its mechanism remains to be elucidated. This study aimed to explore the regulation mechanism of BSHXD in decidualization from its intervention in autophagy so as to rationalize its potential as a novel therapeutic regime for URSA. Decidua tissues were collected from patients with URSA and healthy pregnant women who underwent legal terminations for non-medical reasons at the first trimester. Besides, cell line T-hESCs was utilized to establish induced decidualization model, and were randomly divided into ESC group, DSC group, 3-MA group, AMPK siRNA group, scrambled siRNA group and AMPK siRNA + BSHXD group. Transmission electron microscopy, Monodansylcadaverine (MDC) assay, qRT-PCR, immunohistochemistry, immunofluorescence and Western blotting were used to evaluate the level of decidualization, autophagy and activation of AMPK signaling pathway in decidua tissues and cell experiments. Experiments on decidua tissues showed that decidualization was impaired in URSA with inhibited autophagy. Besides, pAMPK T172 and pULK1 S556 were decreased, and pmTOR S2448 and pULK1 S757 were increased. Cell experiments showed that the level of autophagy increased during induced decidualization, but when autophagy was inhibited, decidualization was impaired. In addition, AMPK/mTOR/ULK1 affected decidualization by mediating autophagy, and BSHXD improved decidualization through this mechanism. In conclusion, this study clarified that the inhibition of autophagy mediated by AMPK/mTOR/ULK1 was associated with impaired decidualization, and the intervention of BSHXD on this pathological process may be a vital mechanism for its treatment of URSA. This study laid the foundation for further research and application of BSHXD.

A comparative study of the efficiency and safety of chemotherapy as a therapeutic method for recurrent or resistant gestational trophoblastic neoplasia: A protocol for systematic review and meta-analysis.

BACKGROUND: Gestational trophoblastic neoplasia (GTN) is an infrequent spectrum of placental malignant cases. Generally, single-agent or multiple-agent chemotherapy is used to treat the condition. The condition has a significant impact on women in the childbearing age, which makes post-chemo fertility and obstetrical results a significant contemplation. Nearly 25% of GTN tumors are recurrent, or have a likelihood of relapsing after, the first round of chemotherapy. Therefore, these resistive and recurring lesions require salvage chemotherapy with or without surgical treatment. Therefore, the current meta-analysis and systematic review will assess the effectiveness and level of safety when using chemotherapy to treat women with resistive or recurring GTN. METHODS: The current study will perform a comprehensive systematic search for randomized controlled trials (RCTs) that have assessed the efficacy and safeness of chemo as a line of treatment for women with resistive or recurring GTN. To this end, a search will be conducted on the following electronic databases: Web of Science, MEDLINE, Chinese National Knowledge Infrastructure (CNKI), EMBASE, WanFang database, and the Cochrane Library. The search will cover the period from the inception of databases to May 2021. In order to identify additional related studies, we will manually search the reference lists of suitable research articles and related systematic reviews. A pair of independent authors will review the titles/abstracts of the studies to check if the studies are eligible, which is proceeded by screening the full texts. This study will employ a uniform data extraction table for data extraction. Moreover, based on the Cochrane Risk of Bias Tool, this protocol review also assesses the bias risk in the studies involved. RESULTS: A comprehensive synthesis of existing indication on chemo treatment for women with resistive or recurring GTN. CONCLUSION: The results offer fresh references for evaluating the effectiveness and safeness of chemo-based treatment for women with resistive or recurring GTN. ETHICS AND DISSEMINATION: An ethical approval is not needed as all data are published. REVIEW REGISTRATION NUMBER: May 17, 2021.osf.io/uwky7. (https://osf.io/uwky7/).

Applied Research Glass Ionomer Cement with TiO2 Nanoparticles in Orthodontic Treatment.

In orthodontics treatment, scholars have tried to introduce nano antibacterial materials into the materials used in orthodontics to reduce the occurrence of enamel demineralization, caries and periodontitis. The experiment investigated the effect of adding titanium dioxide nanoparticles in different proportions on the flexural strength, compressive strength, surface hardness, tribological properties, adhesion properties, fluorine release properties and antibacterial properties of glass ionomer cement. The effect of water cement on orthodontics, the experiment added different proportions of titanium dioxide nanoparticles to traditional glass ion cement, which greatly improved the mechanical strength of glass ion cement, and significantly improved the antibacterial effect of glass ion cement, bending strength, compressive strength and surface hardness. The addition of titanium dioxide nanoparticles produced a significant antibacterial effect on Streptococcus mutants. Nano- TiO2 glass ionomer cement has a significant effect on orthodontics, and the damage to patients' teeth is significantly lower, which is worthy of clinical popularization.

Two Mixed-ligand Coordination Polymers: Treatment Activity on Acute Oral Mucositis during Orthodontic Process by Reducing Inflammatory Response.

By modulating the metal centers to adjust the coordination surroundings of the products, two mixed-linker coordination polymers [Cu2(L)(biz)(OH)]·H2O (1) and [Zn(HL)(biz)] (2) (H3L = 5-(4-carboxybenzyloxy)isophthalic acid, biz = benzimidazole), have been produced under mild hydrothermal conditions. To develop new candidates for the acute oral mucositis during orthodontic process, the acute oral mucositis rat model was constructed and the enzyme linked immunosorbent assay (ELISA) was used to find out the release levels of inflammatory cytokines Tumor Necrosis Factor-α (TNF-α) and Interleukin-1ß (IL-1ß). Next, the activation of the AKT signaling pathway was estimated through judging the relative expression of the inflammatory genes in the oral mucosa cells via reverse transcription-polymerase chain reaction (RT-PCR). After compounds treatment, the expression level of the AKT signaling pathway was evaluated by a western blot. Finally, the quantity of the reactive oxygen species (ROS) in the oral mucosa cells was gauged with ROS detection kit. All the results in this research indicated the much more excellent treatment activity of compound 1 than 2 on the acute oral mucositis.

Local Coverage Optimization Strategy Based on Voronoi for Directional Sensor Networks.

In this paper, we study the area coverage of directional sensor networks (DSNs) with random node distribution. The coverage of DSNs depends on the sensor's locations, the sensing radiuses, and the working directions, as well as the angle of view (AoV), which is challenging to analyze. We transform the network area coverage problem into cell coverage problems by exploiting the Voronoi diagram, which only needs to optimize local coverage for each cell in a decentralized way. To address the cell coverage problem, we propose three local coverage optimization algorithms to improve the cell coverage, namely Move Inside Cell Algorithm (MIC), Rotate Working Direction Algorithm (RWD) and Rotation based on boundary (RB), respectively. Extensive simulations are performed to prove the effectiveness of our proposed algorithms in terms of the coverage ratio.