Electrospun Poly-l-Lactic Acid Membranes Promote M2 Macrophage Polarization by Regulating the PCK2/AMPK/mTOR Signaling Pathway.

Electrospun membranes are widely used in tissue engineering. Regretfully, there is limited research on how its morphological characteristics precisely regulate macrophage activation and immune response. Therefore, electrospun poly-l-lactic acid (PLLA) membranes with different alignments (align and random) and diameters (nanoscale and microscale) are prepared to investigate the effects of different surface morphologies on M2 macrophage polarization. Additionally, transcriptome, proteome, and phosphoproteome sequencings are combined to examine the underlying regulatory mechanisms. The results show that the electrospun PLLA membranes with different surface morphologies have good biocompatibility and can regulate the phenotype and function of macrophages by changing the micromorphology of the matrix surface. Especially, macrophages cultured on the electrospun membranes of the A600 group exhibit higher M2 macrophage polarization than the other three groups. Furthermore, the findings demonstrate that electrospun PLLA membranes enhance AMP-activated protein kinase (AMPK)/ mammalian target of rapamycin (mTOR) signaling activation by upregulating the expression of integrin phosphoenolpyruvate carboxykinase 2 (PCK2), which is critical for M2 macrophage polarization. Taken together, electrospun PLLA membranes promote M2 macrophage polarization by regulating the PCK2/AMPK/mTOR signaling pathway. This research can provide further theoretical bases for scaffold design, immunoregulatory mechanisms, and clinical application based on electrospinning technology in the future.

Balloon Pressure and Clinical Effectiveness of Percutaneous Microballoon Compression in the Treatment of Primary Trigeminal Neuralgia.

BACKGROUND: Primary trigeminal neuralgia (PTN) is a type of chronic neuropathic pain disorder caused by neurovascular compression. Percutaneous balloon compression (PBC) is a widely used method for the treatment of PTN. OBJECTIVES: To examine the correlation of balloon pressure (BP) during percutaneous microballoon compression (PBC) with postoperative pain relief and complications in the treatment of primary trigeminal neuralgia (PTN). STUDY DESIGN: Forty-five patients diagnosed with PTN and treated with PBC were recruited. The BP was recorded at 2 time points: when the balloon achieved the ideal pear shape (initial BP [IBP]) and when the pressure was maintained for 2 min (final BP [FBP]). SETTING: This study was conducted at the Department of Pain and Rehabilitation of the Second Affiliated Hospital at the University of South China in Hunan, China. METHODS: The patients' Barrow Neurological Institute (BNI) pain intensity score, BNI facial numbness score, masticatory muscle weakness score, and recurrence were recorded before and after surgery. The receiver operating characteristic (ROC) curves were generated for the IBP to predict treatment effectiveness, severe facial numbness, and severe masticatory muscle weakness. RESULTS: The BNI pain intensity score, BNI facial numbness score, and masticatory muscle weakness score were significantly decreased after surgery (all P < 0.001). IBP was positively correlated with the difference between IBP and FBP (P < 0.01). Both IBP and the difference between IBP and FBP were negatively correlated with the BNI pain intensity score and positively correlated with the BNI facial numbness score and masticatory muscle weakness score (P < 0.01). The IBP and the difference between the IBP and FBP were significantly lower in patients experiencing recurrence than in the nonrecurrent group (P < 0.05). The areas under the ROC curves of the IBP for predicting effective pain relief, severe facial numbness, and severe masticatory muscle weakness were 0.875, 0.980, and 0.988, respectively. LIMITATIONS: The sample size was relatively small, and the follow-up time was short. The correlations between the BP and other factors, such as filling amount, Meckel's cavity, and the size of the foramen ovale, were not investigated. The impact of the BP on long-term postoperative outcomes was not explored. CONCLUSIONS: An intraoperative BP of 138.65-153.90 KPa can be maintained for effective PBC treatment without causing serious complications.

Intrathecal morphine delivery at prepontine cistern to control refractory cancer-related pain: a case report of extensive metastatic and refractory cancer pain.

BACKGROUND: Extensive metastatic and refractory cancer pain is common, and exhibits a dissatisfactory response to the conventional intrathecal infusion of opioid analgesics. CASE PRESENTATION: The present study reports a case of an extensive metastatic esophageal cancer patient with severe intractable pain, who underwent translumbar subarachnoid puncture with intrathecal catheterization to the prepontine cistern. After continuous infusion of low-dose morphine, the pain was well-controlled with a decrease in the numeric rating scale (NRS) of pain score from 9 to 0, and the few adverse reactions to the treatment disappeared at a low dose of morphine. CONCLUSIONS: The patient achieved a good quality of life during the one-month follow-up period.

Physicochemical properties and micro-interaction between micro-nanoparticles and anterior corneal multilayer biological interface film for improving drug delivery efficacy: the transformation of tear film turnover mode.

Recently, various novel drug delivery systems have been developed to overcome ocular barriers in order to improve drug efficacy. We have previously reported that montmorillonite (MT) microspheres (MPs) and solid lipid nanoparticles (SLNs) loaded with the anti-glaucoma drug betaxolol hydrochloride (BHC) exhibited sustained drug release and thus intraocular pressure (IOP) lowering effects. Here, we investigated the effect of physicochemical particle parameters on the micro-interactions with tear film mucins and corneal epithelial cells. Results showed that the MT-BHC SLNs and MT-BHC MPs eye drops significantly prolonged the precorneal retention time due to their higher viscosity and lower surface tension and contact angle compared with the BHC solution, with MT-BHC MPs exhibiting the longest retention due to their stronger hydrophobic surface. The cumulative release of MT-BHC SLNs and MT-BHC MPs was up to 87.78% and 80.43% after 12 h, respectively. Tear elimination pharmacokinetics study further confirmed that the prolonged precorneal retention time of the formulations was due to the micro-interaction between the positively charged formulations and the negatively charged tear film mucins. Moreover, the area under the IOP reduction curve (AUC) of MT-BHC SLNs and MT-BHC MPs was 1.4 and 2.5 times that of the BHC solution. Accordingly, the MT-BHC MPs also exhibit the most consistent and long-lasting IOP-lowering effect. Ocular irritation experiments showed no significant toxicity of either. Taken together, MT MPs may have the potential for more effective glaucoma treatment.

LncRNA MIR22HG promotes osteoarthritis progression via regulating miR-9-3p/ADAMTS5 pathway.

Dysregulation of long non-coding RNAs (lncRNAs) plays a fundamental role in the development and progression of osteoarthritis (OA), but the potential functions of lncRNAs in OA were not fully clarified. In the present work, we want to clarify the underlying functions and mechanisms of MIR22HG in OA. qRT-PCR was employed to detect the mRNA expression of MIR22HG, miR-9-3p, and ADAMTS5, while the protein expressions were measured using Western blot. The cell proliferation was examined through CCK8, while apoptosis was used in flow cytometry. Luciferase reporter assay and RNA immunoprecipitation (RIP) assays were undertaken to investigate the binding relationship among MIR22HG, ADAMTS5, and miR-9-3p. MIR22HG was significantly overexpressed in OA cartilages, OA chondrocytes and IL-1ß-induced chondrocytes. Functionally, MIR22HG knockdown promoted cell proliferation, suppressed apoptosis, and contributed to downregulation of MMP13 and ADAMTS5 and upregulation of COL2A1 and ACAN in IL-1ß-stimulated chondrocytes. Mechanistically, bioinformatic analysis indicated that MIR22HG may serve as a sponge for miR-9-3p and ADAMTS5 may be a potential targeted gene for miR-9-3p, which were subsequently verified through a dual-luciferase reporter assay. Moreover, rescue experiments showed that MIR22HG participated in the regulation of chondrocytes proliferation, apoptosis, and degradation of extracellular matrix via miR-9-3p/ADAMTS5 pathway. In conclusion, our findings illuminated that inhibition of MIR22HG ameliorated IL-1ß-induced apoptosis and ECM degradation of human chondrocytes through miR-9-3p/ADAMTS5 pathway, which may provide a potentially promising target for OA treatment.

Anti-nociceptive effect of Portulaca oleracea L. ethanol extracts attenuated zymosan-induced mouse joint inflammation via inhibition of Nrf2 expression.

The aim of this study was to explore the effects of ethanol extracts from Portulaca oleracea L. (ePO) on joint inflammation and to explain the underlying mechanisms. A joint inflammation mouse model was constructed by injecting zymosan, and the Von Frey method was employed and the joint thickness measured. The numbers of leukocytes, neutrophils, and monocytes were counted in the joint cavity and the infiltration of inflammatory cells was assessed by joint histopathological analysis. The mRNA levels of inflammatory cytokines were determined by quantitative RT-PCR and their secretion levels were determined by specific ELISAs. Pre-treatment with ePO inhibited articular mechanical hyperalgesia and edema and ameliorated the recruitment of mononuclear neutrophils and leukocytes. In addition, pre-treatment with ePO improved pathological alternations in the joint tissues by reducing the number of inflammatory cells. Pre-treatment with ePO regulated the nuclear factor erythroid 2-related factor 2 (Nrf2)-related proteins and thereby inhibited oxidative stress. In addition, ePO inhibited NLR family pyrin domain containing 3 (NLRP3) inflammasome-related genes (NLRP3, ASC, pro-caspase-1 and pro-IL-1ß), modulated inflammatory cytokines and the activation of NF-κB. ePO attenuated zymosan-induced joint inflammation by regulating oxidative stress, NLRP3 inflammasome, and NF-κB.