Unveiling EFNB2 as a Key Player in Sorafenib Resistance: Insights from Bioinformatics Analysis and Functional Validation in Hepatocellular Carcinoma.

Sorafenib resistance has become a big hurdle for treating advanced HCC; thus, identifying novel targets to overcome sorafenib resistance is of great importance. Thanks to the massive progress in the sequencing and data analysis, high-throughput screening of novel targets in HCC development has been extensively used in recent years. In present study, we harnessed the public dataset and aimed to identify novel targets related to sorafenib resistance in HCC via bioinformatics analysis and in vitro validation. This study examined three GEO datasets (GSE140202, GSE143233, GSE182593) and identified 20 common DEGs. Functional enrichment analysis suggested these DEGs might play a role in regulating drug resistance pathways. PPI network analysis pinpointed 14 hub genes, with EFNB2 showing high connectivity to other genes. Subsequent in vitro experiments demonstrated that EFNB2 was up-regulated in sorafenib-resistant HCC cells. EFNB2 suppression sensitized HepG2 and Huh7 sorafenib-resistant cells. Furthermore, EFNB2 knockdown increased caspase-3/-7 activities and hindered EMT in sorafenib-resistant HCC cells. Conversely, EFNB2 overexpression promoted sorafenib resistance, decreased caspase-3/-7 activity, and enhanced EMT in HCC cells. Overall, this study identified 14 promising genes potentially linked to sorafenib resistance in HCC, with EFNB2 emerging as a potential contributor to this resistance mechanism.

A Report of Two Cases of Meningoencephalitis Caused by Streptococcus intermedius.

Objective: In this paper, we analyzed the clinical data of patients with meningoencephalitis caused by Streptococcus intermedius to understand better the clinical characteristics of the disease and recommend auxiliary diagnostic mode as well as treatment experience. Methods: We reviewed the clinical data of two patients admitted to our department in 2019 with meningoencephalitis caused by S. intermedius. Results: Two female patients were examined, one of whom had a history of radiotherapy for nasopharyngeal carcinoma while the other had no underlying disease. These two patients were admitted with symptoms of meningoencephalitis. Cerebrospinal fluid examinations revealed elevated levels of leukocytes and protein. After treatment with meropenem, the condition improved for a brief time, but then worsened with a decline in mental status and limb movement. Blood and cerebrospinal fluid cultures demonstrated the absence of pathogenic bacteria, while genome sequencing of cerebrospinal fluids revealed the presence of S. intermedius. Cranial magnetic resonance imaging revealed multiple cerebral abscesses (CAs). After coadministration of linezolid as an anti-infective, clinical symptoms gradually improved, and the CAs shrank on follow-up imaging. The condition exhibited a pattern of improvement-deterioration-improvement. Conclusion: Meningoencephalitis caused by S. intermedius is complex and prone to fluctuation and formation of multiple CAs. The definitive clinical diagnosis of this disease can be aided by genome sequencing technology, and early clarification of the etiology combined with the use of potent antibiotics is effective.

Randomized, Single-Blind, Comparative Study of Remimazolam Besylate vs Propofol for Facial Plastic Surgery.

BACKGROUND: Use of local anesthesia and conscious sedation with a combination of a sedative and anesthetic drug during a surgical procedure is an approach designed to avoid intubation, which produces fewer adverse events compared to general anesthesia. In the present study, a comparison was made between the efficacy and safety of remimazolam besylate and propofol for facial plastic surgery. OBJECTIVES: The objective was to evaluate the clinical efficacy, comfort, and incidence of adverse events of remimazolam compared with propofol combined with alfentanil in outpatient facial plastic surgery. METHODS: In this randomized, single-blind, single-center, comparative study, facial plastic surgery patients were randomly divided into remimazolam-alfentanil (n = 50) and propofol-alfentanil (n = 50) groups for sedation and analgesia. The primary endpoint was the incidence of hypoxemia, while secondary endpoints included efficacy and safety evaluations. RESULTS: There were no significant differences regarding the surgical procedure, sedation and induction times, pain and comfort scores, muscle strength recovery, heart rate, respiratory rate, and blood pressure, but the dosage of alfentanil administered to the remimazolam group (387.5 µg) was lower than that for the propofol group (600 µg). The incidence of hypoxemia (P = .046) and towing of the mandibular (P = .028), as well as wake-up (P = .027) and injection pain (P = .008), were significantly higher in the propofol group than the remimazolam group. CONCLUSIONS: Remimazolam and propofol had similar efficacies for sedation and analgesia during facial plastic surgery, but especially the incidence of respiratory depression was significantly lower in patients given remimazolam.

Progesterone-Induced miR-145/miR-143 Inhibits the Proliferation of Endometrial Epithelial Cells.

Our previous study showed that progesterone (P4) can specifically regulate the expression of some microRNAs (miRNAs) in endometrial epithelium. In the present study, we verified the P4-dependent expression of miR-145/miR-143 in endometrial epithelial cells, explored the regulative mechanism of the P4 receptor (PR), and investigated their effects on the proliferation of endometrial epithelial cells. Our results showed that P4 can induce the expression of miR-145/143 in endometrial epithelial cells by acting on the PR A subtype. P4-induced miR-145/143 can inhibit the expression of cyclin D2 by binding to cyclin D2 mRNA 3'UTR. It can also inhibit cell proliferation in mouse endometrial epithelium by arresting the cell cycle during the G1-S checkpoint. Furthermore, miR-145 and miR-143 can inhibit the proliferation of human endometrial cancer cells. In conclusion, P4-induced miR-145/miR-143 is an important regulator in the proliferation of endometrial epithelial cells, and it can also inhibit the proliferation of human endometrial cancer cells. Our study indicates miRNAs are important mechanism of P4 in inhibiting the proliferation of endometrial epithelial cells. And these miRNAs are potential candidates for the diagnosis of endometrial cancer and therapeutic targets.

Preparation of polymethacrylate monolith modified with cysteine for the determination of Cr(iii) ions.

In this study, a simple and rapid polymer monolith microextraction procedure was developed for the determination of Cr(iii) ions by inductively coupled plasma-atomic emission spectrometry. A monolithic column modified with cysteine was synthesized and characterized by scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, thermal gravimetric analysis, specific surface area analysis and pore size distribution analysis. The influences of analytical parameters such as sample pH, adsorption time, eluent type, and coexisting ions were examined. The limit of detection (LOD) and limit of quantification (LOQ) for Cr(iii) ions were 0.005 µg mL-1 and 0.017 µg mL-1, and the relative standard deviation (RSD) was 7.4% (n = 5). The prepared cysteine functionalized monolithic column displayed good enrichment capacity and was successfully applied to the determination of Cr(iii) ions in real samples.

Progesterone-Induced miR-152 Inhibits the Proliferation of Endometrial Epithelial Cells by Downregulating WNT-1.

Progesterone (P4) is an important ovarian hormone that inhibits estrogen-dependent proliferation of endometrial epithelial cells (EECs). miR-152 has been reported to be a cell cycle regulator. In this study, we first demonstrated that P4 induced the expression of miR-152 in ovariectomized mice and Ishikawa cell. miR-152 was detected in the human endometrial cell lines that were stably transfected with P4 receptor. Results showed that P4 induced its expression through its receptor B subtype. Then, using the specific miRNA mimic and inhibitor, we proved that miR-152 impeded G1/S transition in the cell cycle of EECs and inhibited cellular proliferation via downregulating WNT-1 in mice and human endometrial cancer cell lines (Ishikawa, HEC-1-b, and KLE). miR-152 induced by P4 is an important inhibitor for the proliferation of EECs. miR-152 may be an important tumor suppressor microRNA in endometrial cancer.

[Progesterone-induced microRNA-1a inhibits the proliferation of endometrial epithelial cells].

The aim of the present study was to investigate the effects of progesterone (P4)-induced microRNA-1a (miR-1a) on the proliferation of endometrial epithelial cells (EECs) and the underlying mechanism. In vivo, following subcutaneous injection of estradiol (E2) alone (E2 group) or combined injections of E2 and P4 (E2P4 group) in ovariectomized mice, quantitative real-time PCR (qPCR) was used to check the expression of miR-1a-3p in the directly isolated mouse EECs. The agomir or antagomir specific for miR-1a-3p was injected into one side of the uterine horns of ovariectomized mice pretreated with E2 alone or in combination with P4, and the non-specific control agomir or antagomir was injected into their contralateral horns. Flow cytometry was used to analyze the cell cycle of EECs. Immunohistochemistry (IHC) was used to examine the location and expression of cyclin D2, cyclin E1, and cyclin E2 in the uterine tissue sections. In vitro, primary cultured mouse EECs were pretreated with E2 alone (E2 group) or in combination with P4 (E2P4 group). qPCR was used to detect the expression of miR-1a-3p. Exogenous mimic of miR-1a-3p was transfected into E2-pretreated EECs, and EdU incorporation analysis was used to test the proliferation activity of the EECs. The result of in vivo experiment showed that the expression of miR-1a-3p in E2P4 group was significantly higher than that in E2 group (P < 0.05). The miR-1a-3p agomir arrested cell cycle at G1 to S transition in the mice injected subcutaneously with E2 alone (P < 0.05). Conversely, silencing of miR-1a-3p with transfection of miR-1a-3p antagomir promoted the entry of cells into S phase in the mice injected subcutaneously with both E2 and P4 (P < 0.05). The expressions of cyclin E1 and cyclin E2, except for cyclin D2, in uterine sections were also dramatically reduced by miR-1a-3p overexpression in the uterine epithelium (P < 0.05). In vitro, miR-1a-3p was not expressed in the cells of both E2 and E2P4 groups. The mimic of miR-1a-3p decreased EECs proliferation activity (P < 0.05). These results indicate that P4-induced miR-1a can inhibit the expression of cyclin E1 and cyclin E2, consequently suppressing the proliferation of mouse EECs by arresting cells at G1/S phase.

[Effect of Progesterone-induced MicroRNA-152 on the Proliferation of Endometrial Epithelial Cells].

OBJECTIVE: To determine the expression of microRNA-152 induced by progesterone and its effect on the proliferation of endometrial epithelial cells (EECs). METHODS: Cultured EECs, Ishikawa were divided into four groups: control group (C group), 10(-8) mol/L estrogen treated group (E group), 10(-6) mol/L progesterone group (P group) and estrogen plus progesterone treated group (E&P group). The expression of mature microRNA-152 (microRNA-152-3p) of was detected by qRT-PCR. The estrogen treated cells were transfected with mimic-microRNA-152-3p. The estrogen and progesterone treated cells were transfected with inhibitor-microRNA-152-3p. Cell proliferations were detected by CCK-8 assay. The target gene of microRNA-152-3p proteins was predicted using microRNA target databases and validated by Western blot. RESULTS: qRT-PCR showed no difference between C and E groups (P > 0.05) in the expression of microRNA-152-3p. P group had higher expressions of microRNA-152-3p than C group (P < 0.05). E&P group had higher expressions of microRNA-152-3p than C group and P group. MicroRNA target protein prediction suggested that CDC14A is one of direct target proteins of microRNA-152-3p. The results of CCK-8 assay showed that mimic-microRNA-152-3p transfection blocked proliferations of estrogen treated cells and lowered expressions of CDC14A in these cells; while inhibitor-microRNA-152-3p promotes proliferations of estrogen and progesterone treated cells and increased expressions of CDC14A in these cells. CONCLUSION: Progesterone may suppress proliferations of EECs through inducing expressions of microRNA-152-3p. CDC14A is probably one target protein of microRNA-152-3p for its action on EECs.

Identification and characterization of progesterone- and estrogen-regulated MicroRNAs in mouse endometrial epithelial cells.

In endometrial epithelial cells, progesterone (P4) functions in regulating the cell structure and opposing the effects of estrogen. However, the mechanisms of P4 that oppose the effects of estrogen remain unclear. MicroRNAs (miRNAs) are important posttranscriptional regulators that are involved in various physiological and pathological processes. Whether P4 directly induces miRNA expression to antagonize estrogen in endometrial epithelium is unclear. In this study, total RNAs were extracted from endometrial epithelium of ovariectomized mice, which were treated with estrogen alone or a combination of estrogen and P4. MicroRNA high-throughput sequencing with bioinformatics analysis was used to identify P4-induced miRNAs, predict their potential target genes, and analyze their possible biological functions. We observed that 146 mature miRNAs in endometrial epithelial cells were significantly upregulated by P4. These miRNAs were extensively involved in multiple biological processes. The miRNA-145a demonstrated a possible function in the antiproliferative action of P4 on endometrial epithelial cells.

Vitellogenin mediates phagocytosis through interaction with FcγR.

Vitellogenin (Vg), once reported to be a female-specific protein, has been identified in both male and juvenile fishes. However, the biological significance of the production of Vg in the male and juvenile fishes is elusive. Our previous studies showed that Vg is an opsonin capable of enhancing phagocytosis, but the mechanism by which Vg mediates phagocytosis is unknown. In this study we demonstrated that Vg-opsonized phagocytosis was characterized by pseudopod extension and depended upon tyrosine kinase. In contrast, inhibition of Rho family proteins and microtubule depolymerization had little effects on Vg-opsonized phagocytosis. Besides, Vg-opsonized phagocytosis was substantially blocked by monoclonal antibodies against FcγRs but not by CR3 antibody. Moreover, theoretical prediction analysis further revealed that Vg had the potency to interact with Fcγ receptors. Finally, the expression of proinflammatory cytokine genes tnf-α and il-1ß was significantly up-regulated by Vg, and this up-regulation was inhibited by selective inhibitors of FcR signaling pathways, wortmannin and piceatannol. Taken together, these results suggest that Vg plays an IgG-like role in that it activates FcγR-mediated phagocytosis, thus establishing an antibody-like function for Vg for the first time.