Involvement of microglial P2X7 receptor in pain modulation.

BACKGROUND: Pain is a rapid response mechanism that compels organisms to retreat from the harmful stimuli and triggers a repair response. Nonetheless, when pain persists for extended periods, it can lead to adverse changes into in the individual's brain, negatively impacting their emotional state and overall quality of life. Microglia, the resident immune cells in the central nervous system (CNS), play a pivotal role in regulating a variety of pain-related disorders. Specifically, recent studies have shed light on the central role that microglial purinergic ligand-gated ion channel 7 receptor (P2X7R) plays in regulating pain. In this respect, the P2X7R on microglial membranes represents a potential therapeutic target. AIMS: To expound on the intricate link between microglial P2X7R and pain, offering insights into potential avenues for future research. METHODS: We reviewed 140 literature and summarized the important role of microglial P2X7R in regulating pain, including the structure and function of P2X7R, the relationship between P2X7R and microglial polarization, P2X7R-related signaling pathways, and the effects of P2X7R antagonists on pain regulation. RESULTS: P2X7R activation is related to M1 polarization of microglia, while suppressing P2X7R can transfer microglia from M1 into M2 phenotype. And targeting the P2X7R-mediated signaling pathways helps to explore new therapy for pain alleviation. P2X7R antagonists also hold potential for translational and clinical applications in pain management. CONCLUSIONS: Microglial P2X7R holds promise as a potential novel pharmacological target for clinical treatments due to its distinctive structure, function, and the development of antagonists.

Facile and Sensitive Acetylene Black-Based Electrochemical Sensor for the Detection of Imatinib.

A facile and sensitive electrochemical sensor for determining imatinib (IMA) was constructed by modifying a glassy carbon electrode (GCE) with a nanocarbon material, acetylene black (AB). The electrochemical behavior of IMA on the prepared GCE/AB was studied using electrochemical techniques, namely, differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy. The direct determination of IMA by the GCE/AB sensor was accomplished using DPV under optimized conditions. The method verification showed that the oxidation peak current was proportional to the concentrations of IMA in the linear ranges of 0.01-0.5 and 0.5-4 µM, with correlation coefficients of 0.9856 and 0.9946, respectively. The limit of detection of the GCE/AB sensor was 0.15 nM. Moreover, the GCE/AB sensor showed good precision and accuracy. Finally, the GCE/AB sensor was successfully applied to determine IMA in human serum samples, and the recoveries were satisfactory.

FGF21 alleviates endothelial mitochondrial damage and prevents BBB from disruption after intracranial hemorrhage through a mechanism involving SIRT6.

BACKGROUND: Disruption of the BBB is a harmful event after intracranial hemorrhage (ICH), and this disruption contributes to a series of secondary injuries. We hypothesized that FGF21 may have protective effects after intracranial hemorrhage (ICH) and investigated possible underlying molecular mechanisms. METHODS: Blood samples of ICH patients were collected to determine the relationship between the serum level of FGF21 and the [Formula: see text]GCS%. Wild-type mice, SIRT6flox/flox mice, endothelial-specific SIRT6-homozygous-knockout mice (eSIRT6-/- mice) and cultured human brain microvascular endothelial cells (HCMECs) were used to determine the protective effects of FGF21 on the BBB. RESULTS: We obtained original clinical evidence from patient data identifying a positive correlation between the serum level of FGF21 and [Formula: see text]GCS%. In mice, we found that FGF21 treatment is capable of alleviating BBB damage, mitigating brain edema, reducing lesion volume and improving neurofunction after ICH. In vitro, after oxyhemoglobin injury, we further explored the protective effects of FGF21 on endothelial cells (ECs), which are a significant component of the BBB. Mitochondria play crucial roles during various types of stress reactions. FGF21 significantly improved mitochondrial biology and function in ECs, as evidenced by alleviated mitochondrial morphology damage, reduced ROS accumulation, and restored ATP production. Moreover, we found that the crucial regulatory mitochondrial factor deacylase sirtuin 6 (SIRT6) played an irreplaceable role in the effects of FGF21. Using endothelial-specific SIRT6-knockout mice, we found that SIRT6 deficiency largely diminished these neuroprotective effects of FGF21. Then, we revealed that FGF21 might promote the expression of SIRT6 via the AMPK-Foxo3a pathway. CONCLUSIONS: We provide the first evidence that FGF21 is capable of protecting the BBB after ICH by improving SIRT6-mediated mitochondrial homeostasis.

Reducing CSF complications by a recycled Hadad's flap combined with autologous mucosa in secondary endoscope transsphenoidal surgery.

Background: Transsphenoidal secondary operations are a minority but not a rare occurrence. How to viably prevent cerebral fluid (CSF)-related complications and confine surgery-caused injury in secondary surgery as minimally as possible is a huge challenge. This article shares our solution of recycling a prior Hadad-Bassagasteguy flap (HBF) along with a using small piece of free autologous mucosa to reconstruct the skull base. Methods: Of 69 patients, fitted criteria were assigned into 2 different groups: a recycled HBF incorporated with an autologous free mucosa and a recycled HBF incorporated with an artificial dura to rebuild the skull base in secondary transsphenoidal surgery. The postoperative morbidities of pseudomeningocele, CSF leakage and meningitis were recorded and analyzed. Results: A recycled HBF incorporated with an autologous mucosa is capable of reducing CSF complications compared to that of the matched group, particularly decreasing the morbidity of meningitis in secondary transsphenoidal surgery. Diabetes mellitus, craniopharyngioma, chordoma and the utilization of artificial dura were independent risk factors for CSF complications in secondary transsphenoidal surgery through univariate and multivariate logistic regression. In addition, diabetes mellitus and artificial dura are more likely to induce CSF leakage and meningitis. Patients suffering from craniopharyngioma are more susceptible to meningitis. Chordoma indiscriminately increased the risk of each CSF complication. Conclusion: A recycled HBF incorporated with an autologous mucosa is reliable for reconstructing the skull base in secondary transsphenoidal surgery, especially for patients simultaneously suffering from diabetes mellitus and central skull base tumors.

Key factors impacting treatment efficiency in actual copper mineral processing wastewater by ozonation.

Ozone advanced oxidation has been widely used in water treatment, but little research has been reported on the application of ozone to difficult-to-degrade mineral wastewater. In this paper, the effect of ozonation application in the treatment of copper mineral processing wastewater, which is difficult to be effectively treated by traditional processes due to its complex composition, was investigated. The effects of ozonation time, ozone concentration, temperature and pH on the degradation of organic compounds in the wastewater by ozonation were researched. It was found that the chemical oxygen demand (COD) of the wastewater could be reduced by 83.02% by ozonation under optimal treatment conditions. In addition, the mechanism of ozone degradation of the difficult-to-degrade wastewater was studied, and the reasons for the fluctuating variations of COD and ammonia nitrogen during ozonation treatment were explained.

Ligand-gated ion channel P2X7 regulates NLRP3/Caspase-1-mediated inflammatory pain caused by pulpitis in the trigeminal ganglion and medullary dorsal horn.

Emerging research has revealed that the activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasomes contribute to the development of inflammatory and neuropathic pains. In addition, microglia are involved in the central nervous system (CNS) pain conduction. However, the relationship between NLRP3 inflammasome and dental inflammatory pain conduction is yet to be established. Therefore, this study aimed to investigate the roles of P2X7 and NLRP3/Caspase-1 (CASP1) in the inflammatory pain caused by pulpitis using a rat experimental pulpitis model. We discovered that the decreased pain threshold was inversely correlated with the increased expression of NLRP3, Caspase-1, P2X7, interleukin-1ß (IL-1ß), and IL-18 in the trigeminal ganglion and dorsal horn of the medulla after dental pulp exposure. Furthermore, the pain threshold of rats caused by pulpitis was increased by intraperitoneal injection of Brilliant Blue G (BBG), a P2X7 inhibitor, and the expression levels of NLRP3 and related inflammatory factors IL-1ß and IL-18 were decreased. Moreover, treatment with 130 nM KCl, a P2X7 inhibitor, significantly reduced the expression of NLRP3, IL-1ß, IL-18, Caspase-1, and P2X7 in microglia after lipopolysaccharide(LPS) stimulation. In conclusion, our findings suggest that NLRP3/ CASP1 plays a vital role in the conduction of dental pain; the P2X7regulates NLRP3 pathway in the context of dental inflammatory pain conduction, and inhibiting P2X7 may be a potential strategy for dental inflammatory pain relief.

Ligand-gated ion channel P2X7 regulates hypoxia-induced factor-1α mediated pain induced by dental pulpitis in the medullary dorsal horn.

Dental pulpitis often induces severe pain, and the molecular immune response is remarkable in both peripheral and central nervous system. Accumulating evidence indicates that activated microglia in the medullary dorsal horn (MDH) contribute to dental pulpitis induced pain. The P2X7 receptor plays an important role in driving pain and inflammatory processes, and its downstream target hypoxia-induced factor-1α (HIF-1α) has a crucial role in maintaining inflammation. However, the relationship between P2X7 and HIF-1α in dental inflammatory pain remains unclear. This study demonstrated that the degree of inflammation in the dental pulp tissue became more severe in a time-dependent manner by establishing a rat dental pulpitis model via pulp exposure. Meanwhile, the expression of P2X7, HIF-1α, IL-1ß, and IL-18 in the MDH increased most on the seventh day when the pain threshold was the lowest in the dental pulpitis model. Furthermore, lipopolysaccharides (LPS) increased P2X7-mediated HIF-1α expression in microglia. Notably, the suppression of P2X7 caused less IL-1ß and IL-18 release and lower HIF-1α expression, and P2X7 antagonist Brilliant Blue G (BBG) could alleviate pain behaviors of the dental pulpitis rats. In conclusion, our results provide further evidence that P2X7 is a key molecule, which regulates HIF-1α expression and inflammation in dental pulpitis-induced pain.

The AKT/mTOR Signaling Pathway Was Mediated through the LINC00514/miR-28-5p/TRIM44 Axis.

Objective: Increasing evidence has demonstrated the essential role of lncRNAs in tumorigenesis. LINC00514, a novel lncRNA, was reported to be a promoter of malignant behaviors in cancer, but in pituitary adenoma (PA), its biological functions remain unclear. Methods: Herein, we measured LINC00514 expression by RT-qPCR analysis which indicated a significant elevation of LINC00514 expression in human PA tissues. Moreover, the effect of LINC00514 silencing on PA cell proliferation and invasion was, respectively, examined by CCK-8 and transwell assays. Results: The results showed that LINC00514 deletion markedly inhibited PA cell proliferation and invasion. Besides, investigation on the molecular mechanisms showed that LINC00514 might function as an endogenous RNA (ceRNA) to sponge miR-28-5p and TRIM44 was mediated by LINC00514-derived miR-28-5p in PA cells. Furthermore, the AKT/mTOR signaling pathway was mediated through the LINC00514/miR-28-5p/TRIM44 axis. Conclusion: To sum up, we suggested LINC00514 as a novel therapeutic target for PA treatment.

Magnetic Molecularly Imprinted Polymers for the Rapid and Selective Extraction and Detection of Methotrexatein Serum by HPLC-UV Analysis.

In this work, novel selective recognition materials, namely magnetic molecularly imprinted polymers (MMIPs), were prepared. The recognition materials were used as pretreatment materials for magnetic molecularly imprinted solid-phase extraction (MSPE) to achieve the efficient adsorption, selective recognition, and rapid magnetic separation of methotrexate (MTX) in the patients' plasma. This method was combined with high-performance liquid chromatography-ultraviolet detection (HPLC-UV) to achieve accurate and rapid detection of the plasma MTX concentration, providing a new method for the clinical detection and monitoring of the MTX concentration. The MMIPs for the selective adsorption of MTX were prepared by the sol-gel method. The materials were characterized by transmission electron microscopy, Fourier transform-infrared spectrometry, X-ray diffractometry, and X-ray photoelectron spectrometry. The MTX adsorption properties of the MMIPs were evaluated using static, dynamic, and selective adsorption experiments. On this basis, the extraction conditions were optimized systematically. The adsorption capacity of MMIPs for MTX was 39.56 mgg-1, the imprinting factor was 9.40, and the adsorption equilibrium time was 60 min. The optimal extraction conditions were as follows: the amount of MMIP was 100 mg, the loading time was 120 min, the leachate was 8:2 (v/v) water-methanol, the eluent was 4:1 (v/v) methanol-acetic acid, and the elution time was 60 min. MTX was linear in the range of 0.00005-0.25 mg mL-1, and the detection limit was 12.51 ng mL-1. The accuracy of the MSPE-HPLC-UV method for MTX detection was excellent, and the result was consistent with that of a drug concentration analyzer.

Spontaneous healing of complicated crown-root fractures in children: Two case reports.

BACKGROUND: Complicated crown-root fracture is considered a severe dental trauma and is unlikely to heal without treatment. Usually, dentists have to remove the loose coronal fragment of the fractured tooth and treat the remaining part with multidisciplinary approaches. However, we observed spontaneous healing of fracture in two pediatric cases with a history of complicated crown-root fractures over 4 years ago. CASE SUMMARY: In case 1, a 12-year-old boy complained of pain at tooth 11 following an accidental fall 1 d ago. Clinical examination showed a crack line on the crown of tooth 11. Cone beam computed tomography (CBCT) images of tooth 11 showed signs of hard tissue deposition between the fractured fragments. The patient recalled that tooth 11 had struck the floor 1 year ago without seeking any other treatment. In case 2, a 10-year-old girl fell down 1 d ago and wanted to have her teeth examined. Clinical examination showed a fracture line on the crown of tooth 21. CBCT images of tooth 21 also showed signs of hard tissue deposition between the fractured fragments. She also had a history of dental trauma 1 year ago and her tooth 11 received dental treatment by another dentist. According to her periapical radiograph at that time, tooth 21 was fractured 1 year ago and the fracture was overlooked by her dentist. Both of these two cases showed spontaneous healing of complicated crown-root fractures. After over 4 years of follow-up, both fractured teeth showed no signs of abnormality. CONCLUSION: These findings may provide new insights and perspectives on the management and treatment of crown-root fractures in children.

MicroRNA-22 suppresses NLRP3/CASP1 inflammasome pathway-mediated proinflammatory cytokine production by targeting the HIF-1α and NLRP3 in human dental pulp fibroblasts.

AIM: To investigate the synergetic regulatory effect of miR-22 on HIF-1α and NLRP3, subsequently regulating the production of the NLRP3/CASP1 inflammasome pathway-mediated proinflammatory cytokines IL-1ß and IL-18 in human dental pulp fibroblasts (HDPFs) during the progression of pulpitis. METHODOLOGY: Fluorescence in situ hybridization (FISH) and immunofluorescence (IF) were performed to determine the localization of miR-22-3p, NLRP3 and HIF-1α in human dental pulp tissues (HDPTs). The miR-22 mimics and inhibitor or plasmid of NLRP3 or HIF-1α were used to upregulate or downregulate miR-22 or NLRP3 or HIF-1α in HDPFs, respectively. Computational prediction via TargetScan 5.1 and a luciferase reporter assay were conducted to confirm target association. The mRNA and protein expression of HIF-1α, NLRP3, caspase-1, IL-1ß and IL-18 were determined by qRT-PCR and western blotting, respectively. The release of IL-1ß and IL-18 was analysed by ELISA. The significance of the differences between the experimental and control groups was determined by one-way analysis of variance, p < .05 indicated statistical significance. RESULTS: A decrease in miR-22 and an increase in HIF-1α and NLRP3 in HDPTs occurred during the transformation of reversible pulpitis into irreversible pulpitis compared with that in the healthy pulp tissues (p < .05). In the normal HDPTs, miR-22-3p was extensively expressed in dental pulp cells. HIF-1α and NLRP3 were mainly expressed in the odontoblasts and vascular endothelial cells. Whereas in the inflamed HDPTs, the odontoblast layers were disrupted. HDPFs were positive for miR-22-3p, HIF-1α and NLRP3. Computational prediction via TargetScan 5.1 and luciferase reporter assays confirmed that both NLRP3 and HIF-1α were direct targets of miR-22 in HDPFs. The miR-22 inhibitor further promoted the activation of NLRP3/CASP1 inflammasome pathway induced by ATP plus LPS and hypoxia (p < .05). In contrast, the miR-22 mimic significantly inhibited the NLRP3/CASP1 inflammasome pathway activation induced by ATP plus LPS and hypoxia (p < .05). CONCLUSION: MiR-22, as a synergetic negative regulator, is involved in controlling the secretion of proinflammatory cytokines mediated by the NLRP3/CASP1 inflammasome pathway by targeting NLRP3 and HIF-1α. These results provide a novel function and mechanism of miR-22-HIF-1α-NLRP3 signalling in the control of proinflammatory cytokine secretion, thus indicating a potential therapeutic strategy for future endodontic treatment.

Corrigendum to "Nav1.7 via Promotion of ERK in the Trigeminal Ganglion Plays an Important Role in the Induction of Pulpitis Inflammatory Pain".

[This corrects the article DOI: 10.1155/2019/6973932.].

miR-199a-5p suppresses epithelial- mesenchymal-transition in anaplastic thyroid carcinoma cells via targeting Snail signals.

MicroRNAs (miRNAs) have been validated to play prominent roles in the occurrence and development of anaplastic thyroid carcinoma (ATC). miR-199a-5p was previously reported to act as a tumor suppressor or oncomiRNA in various types of cancer. However, its accurate expression, function, and mechanism in ATC remain unclear. Here, we find that miR-199a-5p is significantly downregulated in ATC tissues compared with adjacent non-cancerous tissues. Overexpression of miR-199a-5p significantly inhibits migration and invasion of ATC cells in vitro, and lung metastasis in vivo. Importantly, miR-199a-5p suppresses epithelial-mesenchymal transition (EMT) both in vitro and in vivo by targeting Snail. Taken together, this study reveals that miR-199a-5p is critical to the EMT progression in ATC cells. Targeting the pathway described here may be a novel approach for inhibiting metastasis of ATC.

miR-211 alleviates ischaemia/reperfusion-induced kidney injury by targeting TGFßR2/TGF-ß/SMAD3 pathway.

MicroRNA-211 (miR-211) is closely related to apoptosis and plays an important role in ischemia/reperfusion (I/R) injury. Whether miR-211 is involved in the protective effects in renal I/R injury is unknown. In this study, we evaluated the role of miR-211 in human tubular epithelial cells in response to hypoxia-reoxygenation (H/R) stimulation and I/R injury in vitro and in vivo. The results revealed that miR-211 was down-regulated and TGFßR2 was up-regulated in human kidney (HK-2) cells subjected to H/R. Luciferase reporter assay showed that TGFßR2 was a direct target of miR-211. Enforced miR-211 expression decreased H/R-induced HK-2 cell apoptosis and increased cell viability, and targeting miR-211 further increased H/R-induced HK-2 cell apoptosis and decreased cell viability. However, the effect of miR-211 was reversed by targeting TGFßR2 or enforced TGFßR2 expression in miR-211 overexpressing cells or miR-211 downexpressing cells. Moreover, we confirmed that miR-211 interacted with TGFßR2, and regulating TGF-ß/SMAD3 signal. In vivo in mice, miR-211 overexpression ameliorates biochemical and histological kidney injury, reduces apoptosis in mice following I/R. On the contrary, miR-211 downexpressing promoted histological kidney injury and increased apoptosis in mice following I/R. Inhibition of miR-211 or miR-211 overexpression inhibited TGF-ß/SMAD3 pathways or activated TGF-ß/SMAD3 signal pathways in vitro and in vivo, which are critical for cell survival. Our findings suggested that miR-211 suppress apoptosis and relieve kidney injury following H/R or I/R via targeting TGFßR2/TGF-ß/SMAD3 signals. Therefore, miR-211 may be as therapeutic potential for I/R- induced kidney injury.

Skullcapflavone I has a potent anti-pancreatic cancer activity by targeting miR-23a.

Baicalein has been widely studied and showed a potent activity against pancreatic cancer in both in vivo and in vitro studies. Little is known regarding the effects of Skullcapflavone I (SFI), despite they have similar structures. So, this study was to explore the function of SFI on human pancreatic cancer. Panc-1 cells were transfected with miR-23a precursor, miR-23a inhibitor or the negative controls, and subsequently treated by SFI. Cell viability, Bromodeoxyuridine (BrdU)-positive cell rate, apoptosis, migration, invasion, and related protein expression were assessed by utilizing Cell Counting Kit-8 (CCK-8), BrdU staining, apoptosis assessment, transwell assay, and western blot. SFI significantly reduced the proliferation, migration, and invasion, as well as induced apoptosis of Panc-1 cells. MiR-23a, miR-21, and miR-155 were lowly expressed while miR-145 and miR-146a were highly expressed in SFI-treated cell. Of note, the antitumor effects of SFI were promoted by miR-23a suppression whereas attenuated by miR-23a overexpression. JAK/STAT and MAPK pathways were inhibited by SFI. Also, the pathway inhibition in SFI-treated cells was reversed by miR-23a overexpression. SFI might be a promising anti-pancreatic cancer agent by inhibiting cancer cells growth and motility. The anticancer activities of SFI might be through downregulation of miR-23a, as well as inhibition of JAK/STAT and MAPK pathways.

EIF5A2 Is Highly Expressed in Anaplastic Thyroid Carcinoma and Is Associated With Tumor Growth by Modulating TGF- Signals.

Anaplastic thyroid carcinoma (ATC) is resistant to standard therapies and has no effective treatment. Eukaryotic translation initiation factor 5A2 (EIF5A2) has shown to be upregulated in many malignant tumors and proposed to be a critical gene involved in tumor metastasis. In this study, we aimed to investigate the expression status of EIF5A2 in human ATC tissues and to study the role and mechanisms of EIF5A2 in ATC tumorigenesis in vitro and in vivo. Expression of EIF5A2 protein was analyzed in paraffin-embedded human ATC tissues and adjacent nontumorous tissues (ANCT) (n=24) by immunochemistry. Expressions of EIF5A2 mRNA and protein were analyzed in fresh-matched ATC and ANCT (n=23) and ATC cell lines by real-time polymerase chain reaction (PCR) and Western blotting. The effect of targeting EIF5A2 with short hairpin RNA (shRNA) or EIF5A2 overexpression on the ATC tumorigenesis and TGF-/Smad2/3 signals in vitro and in vivo was investigated. Expression of EIF5A2 was significantly upregulated in ATC tissues and cell lines compared with ANCT and normal follicular epithelial cell line. Functional studies found that targeting EIF5A2 induced SW1736 cell death in vitro and in vivo, followed by significantly downregulated phosphorylation of Smad2/3 (p-Smad2/3) in SW1736 cells at the protein level. Ectopic expression of EIF5A2 could promote 8505C cell growth in vitro and in vivo, followed by significantly upregulated p-Smad3 at the protein level. Recombinant human TGF-1 (hTGF-1) treatment decreased the antiproliferative activity of the EIF5A2 downexpressing 8505C cells through reversing pSmad2/3. Using the specific inhibitor SB431542 to block TGF- pathway or Smad3 siRNA to knock down Smad3 increased the antiproliferative activity of the EIF5A2-overexpressing 8505C cells through inhibiting pSmad2/3. Our findings indicated that EIF5A2 controled cell growth in ATC cells, and EIF5A/TGF-/Smad2/3 signal may be a potential therapeutic target for ATC treatment.

Serum miR-125b levels associated with epithelial ovarian cancer (EOC) development and treatment responses.

Downexpression of miRs was associated with tumor development, progression, and metastasis. This study explored the serum levels of miR-125b in patients with epithelial ovarian cancer (EOC) and to assess its diagnostic value and monitor treatment responses for patients with EOC. A total of 379 individuals were recruited and assigned to the study groups. RT-qPCR analysis was performed to confirm the association of serum miR-125b levels with tumor stages and treatment responses. The median serum levels of miR-125b in patients with EOC were significantly lower than that of other controls (P < 0.0001). Serum miR-125b in patients with high FIGO stage (III+IV), lymph node metastasis, and chemoresistance were lower than that in patients with early-stage (stage I+ II; P < 0.001), without lymph metastasis (p = 0.032) and chemosensitivity (P < 0.001). Low levels of miR-125b had a poor prognosis in patients with EOC. Using a median value of 0.748 to separate EOC from other controls, the sensitivity and specificity reached 0.76 (95% CI 0.75 to 0.85) and 0.416 (95% CI 0.26 to 0.55), respectively. Serum miR-125b showed a statistically significant difference between preoperative and postoperative patients in surgical patient groups (P = 0.003). Serum miR-125b levels were lower in patients with chemoresistance than that in patients with chemosensitivity (P < 0.0001). Serum miR-125b in combination with serum CA125 improved both sensitivity and specificity in diagnosis of EOC (P < 0.001). This study demonstrated that serum miR-125b levels were a useful diagnostic biomarker and biomarker to predict the responses to chemotherapy in patients with EOC.

WITHDRAWN: Skullcapflavone I has a potent anti-pancreatic cancer activity by targeting miR-23a.

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Nav1.7 via Promotion of ERK in the Trigeminal Ganglion Plays an Important Role in the Induction of Pulpitis Inflammatory Pain.

The trigeminal ganglion (TG) refers to sensory neurons bodies that innervate the spinal cord and peripheral axons that innervate teeth. The tetrodotoxin-sensitive sodium (NA) channels (Nav1.7) play important roles in the pathophysiology of pain. In this study, we investigated the TG expression of Nav1.7 and extracellular signal-regulated kinase (ERK) in a rat model of pulpitis to explore the correlation between these channels and inflammatory pain. Pulpitis was confirmed by hematoxylin-eosin staining. In this study, we demonstrated that the reflex of rats to mechanical stimulation increases after pulp exposure and that the exposed rat molar pulp can upregulate the expression of Nav1.7 and ERK in the rat TG. Three days after rat pulp exposure, the expression levels of the two ion channels in the TG increased. TG target injection of PF04856264, a Nav1.7 inhibitor, dose-dependently increased the mechanical pain threshold and was able to inhibit ERK expression. TG target injection of PD98059, an ERK inhibitor, dose-dependently increased the mechanical pain threshold. These factors simultaneously resulted in the highest production. In this study, with the established link to inflammatory pain, we found that Nav1.7 and ERK both play important roles in the induction of inflammatory pain caused by pulpitis. We also found a correlation between the expression levels of Nav1.7 and ERK and the degree of inflammatory pain. Furthermore, ERK signaling pathways were promoted by the Nav1.7 in TG after pulpitis.

miR-423-5p inhibits the proliferation and metastasis of glioblastoma cells by targeting phospholipase C beta 1.

Glioma is a common brain tumor which is highly invasive, responds poorly to therapy, and has a poor prognosis. There is growing evidence that an abnormal expression of many genes is related to glioma and leads to glioma cell growth and metastasis. Phospholipase C beta 1 (PLCB1) plays critical roles in intracellular transduction and regulating signal activation, which are important to tumorigenesis. Therefore, it could bind to miRNA as a target gene. The purpose of our study was to confirm that PLCB1 plays a critical role in suppressing glioma progression. We found that the expression of miR-423-5p was reduced, but the expression of PLCB1 was increased, in glioma tissues and cells. To explore whether miR-423-5p affects PLCB1, a bioinformatics approach suggested that miR-423-5p can directly target PLCB1. Moreover, we observed, using luciferase reporter assays, that miR-423-5p could target PLCB1 3'-UTR. Functionally, the overexpression of miR-423-5p could attenuate the proliferation, invasion, and migration and promote the apoptosis of glioma cells. Furthermore, we found that miR-423-5p could enhance p-ERK expression in glioma cells. Taken together, we deduced that miR-423-5p inhibited proliferation and metastasis by targeting PLCB1, and it also promotes apoptosis in glioma cells. These results suggest that miR-423-5p directly targets PLCB1 3'-UTR and could inhibit cell invasion and migration through the ERK-dependent pathway in glioma, and the miR-423-5p/PLCB1 axis may be a potential target for new potential therapeutic strategies to treat glioma.