Search

Targeting the unique glioma immune microenvironment is a promising approach in developing breakthrough immunotherapy treatments. However, recent advances in immunotherapy, including the development of immune checkpoint inhibitors, have not improved the outcomes of patients with glioma. A way of monitoring biological activity of immune cells in neural tissues affected by glioma should be developed to address this lack of sensitivity to immunotherapy. Thus, in this study, we sought to examine the feasibility of non-invasive monitoring of glioma-associated microglia/macrophages (GAM) by utilizing our previously developed induced microglia-like (iMG) cells. Primary microglia (pMG) were isolated from surgically obtained brain tissues of 22 patients with neurological diseases. iMG cells were produced from monocytes extracted from the patients peripheral blood. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed a significant correlation of the expression levels of representative markers for M1 and M2 microglia phenotypes between pMG and the corresponding iMG cells in each patient (Spearmans correlation coefficient = 0.5225, P

Purpose Postoperative nausea and vomiting (PONV) is a common adverse event after surgery. Remimazolam is a novel sedative agent recently approved for general anesthesia in Japan. This study evaluated the efficacy of remimazolam in the incidence of PONV after laparoscopic gynecological surgery under general anesthesia. Methods This prospective, randomized controlled trial included 64 women who underwent laparoscopic gynecological surgery. The patients were randomly assigned to undergo general anesthesia with either remimazolam (REM group) or desflurane (DES group, n = 30, each group). The primary outcome was the incidence of PONV in the two groups at 2 h and 24 h after the surgery. The incidence of vomiting, rescue antiemetic use, and severity of nausea were also evaluated. Results In the REM group, the incidence of PONV (27% versus 60%, respectively; P = 0.02), rescue antiemetic use (0 versus 7, respectively; P = 0.01), and nausea score (P = 0.01) were significantly decreased during the first 2 h after surgery. No parameters were significantly different 24 h after surgery between the two groups. Conclusion Remimazolam can reduce the incidence of PONV after laparoscopic gynecological surgery compared to general anesthesia with desflurane during the early postoperative period., Author(s): Yuki Hari [sup.1], Shiho Satomi [sup.2], Chiaki Murakami [sup.1], Soshi Narasaki [sup.2], Atsushi Morio [sup.2], Takahiro Kato [sup.2], Yasuo M. Tsutsumi [sup.2], Nami Kakuta [sup.1], Katsuya Tanaka [sup.1] Author [...]

An autism‐associated gene Shank3 encodes multiple splicing isoforms, Shank3a‐f. We have recently reported that Shank3a/b‐knockout mice were more susceptible to kainic acid‐induced seizures than wild‐type mice at 4 weeks of age. Little is known, however, about how the N‐terminal and ankyrin repeat domains (NT‐Ank) of Shank3a/b regulate multiple molecular signals in the developing brain. To explore the functional roles of Shank3a/b, we performed a mass spectrometry‐based proteomic search for proteins interacting with GFP‐tagged NT‐Ank. In this study, NT‐Ank was predicted to form a variety of complexes with a total of 348 proteins, in which RNA‐binding (n = 102), spliceosome (n = 22), and ribosome‐associated molecules (n = 9) were significantly enriched. Among them, an X‐linked intellectual disability‐associated protein, Nono, was identified as a NT‐Ank‐binding protein. Coimmunoprecipitation assays validated the interaction of Shank3 with Nono in the mouse brain. In agreement with these data, the thalamus of Shank3a/b‐knockout mice aberrantly expressed splicing isoforms of autism‐associated genes, Nrxn1 and Eif4G1, before and after seizures with kainic acid treatment. These data indicate that Shank3 interacts with multiple RNA‐binding proteins in the postnatal brain, thereby regulating the homeostatic expression of splicing isoforms for autism‐associated genes after birth. [ABSTRACT FROM AUTHOR]

Background: Diabetic neuropathic pain is a known complication of diabetes mellitus (DM) and results from the complex interaction of various factors affecting the nervous system. Yokuansan (YKS) is a versatile traditional Japanese herbal medicine with a wide range of applications, especially in pain management and neurological manifestations. YKS has analgesic properties for nerve damage and is a potential treatment for DM-induced neuropathic pain, especially in patients with diabetic neuropathy. Thus, we examined the anti-allodynic effect of YKS on DM-induced neuropathic pain. Methods: All experiments were performed on 6-week-old male Sprague–Dawley rats. DM and diabetic neuropathy were induced in rats with streptozotocin. Mechanical allodynia was assessed using dynamic plantar esthesiometry. Additionally, we conducted an immunological assessment of microglia cell changes in the spinal cord and an experiment to clarify the involvement of serotonin. Results: Diabetes significantly reduced withdrawal thresholds in rats during the initial two weeks of the experiment, which stabilized thereafter. However, this effect was not investigated in the control group. We assessed, using the dynamic plantar test, the anti-allodynic effects of orally administered YKS (1 g/kg). Daily YKS administration significantly increased the withdrawal threshold in DM animals. Additionally, oral YKS reduced the expression of Ibal-1-positive microglia. To elucidate the mechanism of action of YKS, we explored the involvement of serotonin (5-hydroxytryptamine [5-HT]) receptors in mediating its effects. Intrathecal administration of 5-HT receptor antagonists (WAY-100635, ketanserin, and ondansetron) inhibited the protective effects of YKS. Conclusions: YKS exhibited an anti-allodynic effect, suggesting that YKS may activate 5-HT receptors in the spinal cord, thereby alleviating diabetic neuropathic pain. [ABSTRACT FROM AUTHOR]

Herein, epitaxial δ‐Ga2O3 thin films are successfully grown on various planes of yttria‐stabilized zirconia (YSZ) and c‐plane sapphire substrates by inserting the same crystal‐structured β‐Fe2O3 and bcc‐In2O3 buffer layers via mist chemical vapor deposition. X‐ray diffraction (XRD) measurements reveal that various planes of δ‐Ga2O3 thin films are grown in both the out‐of‐plane and in‐plane orientations using the same crystal‐structured buffer layers to reduce the lattice mismatch. δ‐Ga2O3 (111) is demonstrated to grow on the YSZ (111) in the narrow growth temperature range of 575–675 °C due to thermal instability of β‐Fe2O3 buffer layers. Next, a c‐plane sapphire wafer as a substrate using two buffer layers for the growth of δ‐Ga2O3 is investigated. XRD 2θ–ω scan reveals that the mixture of α‐ and δ‐Ga2O3 thin films is grown on Fe2O3/In2O3/c‐plane sapphire. This is because the Fe2O3 buffer layers are phase separated into α and β phases due to the large grain size of the In2O3 buffer layer. XRD φ‐scan profiles indicate that the δ‐Ga2O3 thin film grown on sapphire is composed of a twin domain. This study contributes to our understanding of the growth mechanism of δ‐Ga2O3 and its future applications in devices. [ABSTRACT FROM AUTHOR]