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Multiple studies have shown that astrocytes in the medullary dorsal horn (MDH) play an important role in the development of pathologic pain. However, little is known about the structural reorganization of the peripheral astrocytic processes (PAP), the main functional part of the astrocyte, in MDH in neuropathic state. For this, we investigated the structural relationship between PAP and their adjacent presynaptic axon terminals and postsynaptic dendrites in the superficial laminae of the MDH using electron microscopical immunohistochemistry for ezrin, a marker for PAP, and quantitative analysis in a rat model of neuropathic pain following chronic constriction injury of the infraorbital nerve (CCI-ION). We found that, compared to controls, in rats with CCI-ION, (1) the number, % area, surface density, and volume fraction of ezrin-positive (+) PAP, as well as the fraction of synaptic edge apposed by ezrin + PAP and the degree of its coverage of presynaptic axon terminals and postsynaptic dendrites increased significantly, (2) these effects were abolished by administration of the mGluR5 antagonist 2-methyl-6-(phenylethynyl) pyridine (MPEP). These findings indicate that PAP undergoes structural reorganization around the central synapses of sensory afferents following nerve injury, suggest that it may be mediated by mGluR5, and may represent the structural basis for enhancing astrocyte-neuron interaction in neuropathic pain.
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Importance: Multiple pregnancy is relatively common in many countries and is associated with various pregnancy complications, including preterm birth, low birth weight, and congenital anomalies. In particular, a poorer prognosis has been reported when congenital anomalies overlap with other pregnancy complications in multiple pregnancy compared with singleton pregnancy. Objective: This study reviews the characteristics of congenital anomalies that occur in multiple gestations as compared with singleton pregnancies. Evidence Acquisition: An extensive manual search of major electronic databases was conducted in June 2023. This literature review provides a comprehensive coverage of the congenital anomalies in multiple pregnancy. Results: Most studies have shown that multiple gestations are associated with an increased risk of congenital anomalies compared with singleton pregnancies. In addition, higher rates of congenital anomalies and concordance have been observed in monozygotic versus dizygotic twins. The effect of assisted reproductive therapies on the risk of congenital anomalies appears to be smaller in multiple gestations than in singleton pregnancies. Conclusions: Multiple pregnancy is significantly associated with an increased risk of congenital anomalies. Relevance: This review provides obstetrical providers with the requisite knowledge to offer appropriate antenatal care and prenatal anomaly screening to patients with multiple pregnancies.
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Complicações na Gravidez , Nascimento Prematuro , Gravidez , Humanos , Recém-Nascido , Feminino , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Gravidez Múltipla , Diagnóstico Pré-Natal , Cuidado Pré-Natal , Complicações na Gravidez/epidemiologiaRESUMO
Background and Objectives: Long and ineffective labor causes hardships for mothers and doctors and increases the rate of cesarean sections and medical comorbidities. Several factors contribute to effective and less painful labor, including maternal age, parity, fetal characteristics, and the medications or procedures that obstetricians use for labor. We aimed to study the factors that affect labor duration and identify those that make labor more effective. Materials and Methods: This retrospective study included 141 patients who underwent normal vaginal deliveries at the Daegu Catholic University Medical Center between April 2013 and April 2022. Among the 141 patients, 44 received pethidine intravenously, 88 received oxytocin intravenously, and 64 received epidural anesthesia. The duration of the active phase and second stage of labor were recorded according to the findings of a manual examination of the cervix and continuous external electronic monitoring. We analyzed maternal and neonatal medical records and performed binomial logistic regression to identify the factors associated with a shorter active phase of labor. The clinical outcomes in mothers and neonates were also evaluated. Results: Among the various clinical factors, multiparity (odds ratio of parity 0.325) and the use of pethidine (odds ratio 2.906) were significantly associated with shortening the active phase of labor to less than 60 min. The use of epidural anesthesia or oxytocin was not significantly associated with reducing the active phase of labor. When patients were divided into two groups based on whether a pethidine injection had been used during labor, the duration of the active phase was shorter in the pethidine injection group than in the control group for both nulliparas and multiparas. No significant differences in the duration of the second stage of labor were observed between the pethidine injection and control groups. There were no significant differences in pregnancy outcomes, including the need for mechanical ventilation of neonates, Apgar scores, neonatal intensive care unit admissions, number of precipitous deliveries, maternal adverse side effects of drugs, or duration of maternal hospitalization between the two groups. Conclusions: Pethidine can be safely administered to women during labor to help reduce the duration of the active phase by promoting dilatation of the cervix and preventing complications that may result from prolonged labor. Pethidine may be helpful, especially for those who cannot receive epidural anesthesia or who cannot afford it. However, large-scale randomized controlled studies are required to evaluate the efficacy and safety of this drug during labor. Furthermore, it would be helpful if various studies were conducted depending on the timing of administration and indications for delivery.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Trabalho de Parto , Gravidez , Recém-Nascido , Humanos , Feminino , Estudos Retrospectivos , Índice de Apgar , CesáreaRESUMO
The sustained growth of the market for ophthalmic medical devices has increased the demand for alternatives to animal testing for the evaluation of eye irritation. The International Organization for Standardization has acknowledged the need to develop novel in vitro tests to replace animal testing. Here, we evaluated the applicability of an alternative method based on a human corneal model to test the safety of ophthalmic medical devices. 2-Hydroxyethyl methacrylate (HEMA) and Polymethyl methacrylate (PMMA), which are used to fabricate contact lenses, were used as base materials. These materials were blended with eye irritant and non-irritant chemicals specified in the OECD Test Guideline (TG) 492 and Globally Harmonized System (GHS) classification. Then, three GLP-certified laboratories performed three replicates using the developed method using 3D reconstructed human cornea epithelium, MCTT HCETM. OECD TG 492 describes the procedure used to evaluate the eye hazard potential of the test chemical based on its ability to induce cytotoxicity in a reconstructed human cornea-like epithelium (RhCE) tissue. Results: The within-laboratory reproducibility (WLR) and between-laboratory reproducibility (BLR) were both 100%. When a polar extraction solvent was used, the sensitivity, specificity, and accuracy were all 100% in each laboratory. When a non-polar extraction solvent was used, the sensitivity was 80%, the specificity was 100%, and the accuracy was 90%. The proposed method exhibited excellent reproducibility and predictive capacity within and between laboratories. Therefore, the proposed method using the MCTT HCETM model could be used to evaluate eye irritation caused by ophthalmic medical devices.
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Introduction: Satellite glial cells (SGCs) that envelop the cell bodies of neurons in sensory ganglia have been shown to both release glutamate, and be activated by glutamate in the context of nociceptive signaling. However, little is known about the subpopulations of SGCs that are activated following nerve injury and whether glutamate mechanisms in the SGCs are involved in the pathologic pain. Methods: To address this issue, we used light and electron microscopic immunohistochemistry to examine the change in the glutamate levels in the SGCs and the structural relationship between neighboring neurons in the trigeminal ganglion (TG) in a rat model of craniofacial neuropathic pain, CCI-ION. Results: Administration of ionomycin, ATP and Bz-ATP induced an increase of extracellular glutamate concentration in cultured trigeminal SGCs, indicating a release of glutamate from SGCs. The level of glutamate immunostaining in the SGCs that envelop neurons of all sizes in the TG was significantly higher in rats with CCI-ION than in control rats, suggesting that SGCs enveloping nociceptive as well as non-nociceptive mechanosensitive neurons are activated following nerve injury, and that the glutamate release from SGCs increases in pathologic pain state. Close appositions between substance-P (SP)-immunopositive (+) or calcitonin gene-related peptide (CGRP)+, likely nociceptive neurons, between Piezo1+, likely non-nociceptive, mechanosensitive neurons and SP+ or CGRP+ neurons, and between SGCs of neighboring neurons were frequently observed. Discussion: These findings suggest that glutamate in the trigeminal SGCs that envelop all types of neurons may play a role in the mechanisms of neuropathic pain, possibly via paracrine signaling.
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In this study, ionic conductive hydrogels were prepared with 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS). Acrylic acid (AA), acrylamide (AAm), and 2-hydroxyethyl acrylate (HEA) were used as comonomers to complement the adhesion properties and ion conductivity of AMPS hydrogels. Hydrogels were prepared by irradiating a 20 kGy dose of E-beam to the aqueous monomer solution. With the E-beam irradiation, the polymer chain growth and network formation simultaneously proceeded to form a three-dimensional network. The preferred reaction was determined by the type of comonomer, and the structure of the hydrogel was changed accordingly. When AA or AAm was used as a comonomer, polymer growth and crosslinking proceeded together, so a hydrogel with increased peel strength and tensile strength could be prepared. In particular, in the case of AA, it was possible to prepare a hydrogel with improved adhesion without sacrificing ionic conductivity. When the molar ratio of AA to AMPS was 3.18, the 90° peel strength of AMPS hydrogel increased from 171 to 428 gf/25 mm, and ionic conductivity slightly decreased, from 0.93 to 0.84 S/m. By copolymerisation with HEA, polymer growth was preferred compared with chain crosslinking, and a hydrogel with lower peel strength, swelling ratio, and ionic conductivity than the pristine AMPS hydrogel was obtained.
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Complications related to the vascular anastomosis of the placental vessels in monochorionic twins are fatal. The clinical syndromes of feto-fetal transfusion include twin anemia polycythemia sequence (TAPS), twin-twin transfusion syndrome, and twin reversed arterial perfusion sequence. We present an extremely rare case of TAPS in a dichorionic diamniotic pregnancy. A 36-year-old woman, gravida 0, para 0, was referred to our hospital with suspected preterm premature membrane rupture. Although her pelvic examination did not reveal specific findings, the non-stress test result showed minimal variability in the first fetus and late deceleration in the second one. An emergency cesarean section was performed. The placenta was fused, and one portion of the placenta was pale, while the other portion was dark red. The hemoglobin level of the first fetus was 7.8 g/dL and that of the second one was 22.2 g/dL.
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Microvascular function may be modulated by various anesthetics. Desflurane and propofol anesthesia have different effects on microvascular function. However, there are few reports on the effects of sevoflurane and desflurane on microvascular function during cardiac surgery. We compared the effects of sevoflurane and desflurane on microvascular reactivity, as measured by the vascular occlusion tests (VOTs) during off-pump coronary artery bypass (OPCAB) surgery. Patients undergoing OPCAB were eligible for study inclusion. Patients were excluded if they were unsuitable for treatment with volatile agents or the VOT, had renal failure or uncontrolled diabetes, or were pregnant. The enrolled patients were randomized to receive sevoflurane or desflurane during surgery. Tissue oxygen saturation (StO2) dynamics during the VOT were measured at baseline (pre-anesthesia), pre-anastomosis, post-anastomosis of vessel grafts, and at the end of surgery. Macrohemodynamic variables, arterial blood gas parameters, and in-hospital adverse events were also evaluated. A total of 64 patients (32 in each group) were analyzed. StO2 dynamics did not differ between the groups. Compared to baseline, StO2 and the rate of recovery following vascular occlusion decreased at the end of surgery in both groups (adjusted p-value, < 0.001), and no group difference was observed. Macrohemodynamic variables, blood gas analysis results, and the rate of postoperative in-hospital adverse events were similar between the groups. Microvascular reactivity, as measured by the VOT during OPCAB, showed no difference between the sevoflurane and desflurane groups. Also, there were no group differences in macrohemodynamics or the rate of postoperative adverse events. TRIAL REGISTRATION : Clinicaltrials.gov, identifier NCT03209193; registered on July 3, 2017.
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Anestésicos Inalatórios , Ponte de Artéria Coronária sem Circulação Extracorpórea , Isoflurano , Éteres Metílicos , Propofol , Humanos , SevofluranoRESUMO
BACKGROUND: Our objective was to evaluate risks of adverse obstetric outcomes in pregnancies with myoma(s) or in pregnancies following myomectomy. METHODS: We analyzed the national health insurance database, which covers almost the entire Korean population, between 2004 and 2015. The risks of adverse pregnancy outcomes in pregnancies with myoma(s) or in pregnancies following myomectomy, compared to those in women without a diagnosed myoma, were analyzed in multivariate logistic regression analysis. RESULTS: During the study period, 38,402 women with diagnosed myoma(s), 9890 women with a history of myomectomy, and 740,675 women without a diagnosed myoma gave birth. Women with a history of diagnosed myoma(s) and women with a history of myomectomy had significantly higher risks of cesarean section (aOR 1.13, 95% CI 1.1-1.16 and aOR 7.46, 95% CI 6.97-7.98, respectively) and placenta previa (aOR 1.41, 95% CI 1.29-1.54 and aOR 1.58, 95% CI 1.35-1.83, respectively), compared to women without a diagnosed myoma. And the risk of uterine rupture was significantly higher in women with previous myomectomy (aOR 12.78, 95% CI 6.5-25.13), compared to women without a diagnosed myoma, which was much increased (aOR 41.35, 95% CI 16.18-105.69) in nulliparous women. The incidence of uterine rupture was the highest at delivery within one year after myomectomy and decreased over time after myomectomy. CONCLUSIONS: Women with a history of myomectomy had significantly higher risks of cesarean section and placenta previa compared to women without a diagnosed myoma.
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Cesárea/estatística & dados numéricos , Leiomioma/cirurgia , Miomectomia Uterina/efeitos adversos , Neoplasias Uterinas/cirurgia , Ruptura Uterina/etiologia , Adulto , Cesárea/efeitos adversos , Feminino , Humanos , Modelos Logísticos , Análise Multivariada , Placenta Prévia/etiologia , Gravidez , Complicações na Gravidez/etiologia , Resultado da Gravidez , República da Coreia , Estudos RetrospectivosRESUMO
Sensory discrimination is essential for survival. However, how sensory information is finely controlled in the brain is not well defined. Here, we show that astrocytes control tactile acuity via tonic inhibition in the thalamus. Mechanistically, diamine oxidase (DAO) and the subsequent aldehyde dehydrogenase 1a1 (Aldh1a1) convert putrescine into GABA, which is released via Best1. The GABA from astrocytes inhibits synaptically evoked firing at the lemniscal synapses to fine-tune the dynamic range of the stimulation-response relationship, the precision of spike timing, and tactile discrimination. Our findings reveal a novel role of astrocytes in the control of sensory acuity through tonic GABA release.
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Astrócitos/fisiologia , Inibição Neural/fisiologia , Tálamo/fisiologia , Percepção do Tato/fisiologia , Ácido gama-Aminobutírico/fisiologia , Família Aldeído Desidrogenase 1/metabolismo , Amina Oxidase (contendo Cobre)/metabolismo , Animais , Astrócitos/metabolismo , Astrócitos/ultraestrutura , Bestrofinas/biossíntese , Bestrofinas/genética , Feminino , Antagonistas GABAérgicos , Imuno-Histoquímica , Potenciais Pós-Sinápticos Inibidores/fisiologia , Macrolídeos/farmacologia , Masculino , Camundongos , Camundongos Knockout , Microscopia Eletrônica , Neurônios/metabolismo , Neurônios/fisiologia , Técnicas de Patch-Clamp , Picrotoxina/farmacologia , Cultura Primária de Células , Piridazinas/farmacologia , RNA Interferente Pequeno/farmacologia , Retinal Desidrogenase/metabolismo , Ácido gama-Aminobutírico/biossíntese , Ácido gama-Aminobutírico/farmacologiaRESUMO
Evidence has mounted that insulin can be synthesized in various brain regions, including the hypothalamus. However, the distribution and functions of insulin-expressing cells in the hypothalamus remain elusive. Herein, we show that in the mouse hypothalamus, the perikarya of insulin-positive neurons are located in the paraventricular nucleus (PVN) and their axons project to the median eminence; these findings define parvocellular neurosecretory PVN insulin neurons. Contrary to corticotropin-releasing hormone expression, insulin expression in the PVN was inhibited by restraint stress (RS) in both adult and young mice. Acute RS-induced inhibition of PVN insulin expression in adult mice decreased both pituitary growth hormone (Gh) mRNA level and serum GH concentration, which were attenuated by overexpression of PVN insulin. Notably, PVN insulin knockdown or chronic RS in young mice hindered normal growth via the downregulation of GH gene expression and secretion, whereas PVN insulin overexpression in young mice prevented chronic RS-induced growth retardation by elevating GH production. Our results suggest that in both normal and stressful conditions, insulin synthesized in the parvocellular PVN neurons plays an important role in the regulation of pituitary GH production and body length, unveiling a physiological function of brain-derived insulin.
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Hormônio do Crescimento/metabolismo , Insulina/biossíntese , Núcleo Hipotalâmico Paraventricular/metabolismo , Animais , Hormônio Liberador da Corticotropina/metabolismo , Regulação da Expressão Gênica , Hormônio do Crescimento/genética , Insulina/genética , Insulina/metabolismo , Masculino , Eminência Mediana/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/metabolismo , Somatostatina/genética , Somatostatina/metabolismo , Estresse FisiológicoRESUMO
AIM: The purpose of this study was to evaluate the prognostic factors of patients with stage IIIC1r cervical cancer who underwent concurrent chemoradiotherapy. METHODS: A total of 134 patients treated with chemoradiotherapy for cervical cancer with pelvic and/or paraaortic lymph node metastasis (PALNM) were enrolled in this study. Clinical variables were investigated through review of the patients' medical records. RESULTS: The 5-year overall survival (OS) rate in patients with stage IIICr cervical cancer was 70.5%. Age, PALNM, parametrial invasion, T stage, pelvic side wall invasion, differentiation, lymphovascular space involvement and high squamous cell carcinoma antigen level (>8 ng/mL) were prognostic factors for survival. The 5-year OS rate of patients with stage IIIC1r was 74.5%, and that of stage IIIC2r was 38.1% (P-value = 0.012). The 5-year OS rate of patients with stage IIIC1r with the presence of pelvic side wall invasion was 48.3% and that in its absence was 83.0% (P-value < 0.001). The 5-year OS rate of patients with stage IIIC1r with the presence of parametrial invasion was 68.9% and that in its absence was 82.4% (P-value = 0.031). In multivariable analysis via backward conditional modeling, age, PALNM and pelvic side wall invasion were independent prognostic factors for survival of stage IIICr. Age and pelvic side wall invasion were independent prognostic factors for survival of stage IIIC1r cervical cancer. CONCLUSION: In stage IIICr cervical cancer, patients with PALNM, and/or pelvic side wall invasion can expect to have a poor prognosis. Particularly, pelvic side wall invasion in stage IIIC1r is an independent prognosis factor.
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Carcinoma de Células Escamosas , Neoplasias do Colo do Útero , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia , Feminino , Humanos , Histerectomia , Metástase Linfática , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologiaRESUMO
Ependymal cells (ECs) are multiciliated neuroepithelial cells that line the ventricles of the brain and the central canal of the spinal cord (SC). How ependymal motile cilia are maintained remains largely unexplored. Here we show that zebrafish embryos deficient in Wnt signaling have defective motile cilia, yet harbor intact basal bodies. With respect to maintenance of ependymal motile cilia, plcδ3a is a target gene of Wnt signaling. Lack of Connexin43 (Cx43), especially its channel function, decreases motile cilia and intercellular Ca2+ wave (ICW) propagation. Genetic ablation of cx43 in zebrafish and mice diminished motile cilia. Finally, Cx43 is also expressed in ECs of the human SC. Taken together, our findings indicate that gap junction mediated ICWs play an important role in the maintenance of ependymal motile cilia, and suggest that the enhancement of functional gap junctions by pharmacological or genetic manipulations may be adopted to ameliorate motile ciliopathy.
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Cílios/metabolismo , Conexina 43/metabolismo , Conexinas/metabolismo , Epêndima/metabolismo , Medula Espinal/metabolismo , Peixe-Zebra/embriologia , Animais , Diferenciação Celular , Cílios/genética , Conexina 43/genética , Epêndima/patologia , Junções Comunicantes , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Inativação de Genes , Humanos , Masculino , Camundongos , Camundongos Knockout , Transdução de Sinais/genética , Via de Sinalização Wnt/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismoRESUMO
Background: This study aimed to assess the in-field lymph node (LN) failure rate according to LN size and to investigate effect of LN size on the survival outcome of patients with locally advanced cervical carcinoma treated with concurrent chemoradiotherapy (CCRT). Methods: A total of 310 patients with locally advanced cervical carcinoma treated with CCRT were enrolled in retrospective study. LN status was evaluated by magnetic resonance imaging. All patients received conventional external beam irradiation and high-dose rate brachytherapy, and concurrent cisplatin-based chemotherapy. In-field LN failure rate according to LN size was analyzed. Results: The median follow-up period was 83 months (range, 3-201 months). In-field LN failure rate in patients with pelvic LN size more than 10 mm was significantly higher than that in patients with pelvic LN size less than 10 mm (p<0.001). A similar finding was observed in the in-field para-aortic LN (PALN) failure rate (p=0.024). The pelvic and PALN size (≥10 mm) was a significant prognostic factor of overall-survival (OS) and disease-free survival rate in univariate and multivariate analyses. The OS rate was significantly different between groups according to LN size (<10 mm vs. ≥10 mm). Conclusion: A LN of less than 10 mm in size in an imaging study is controlled by CCRT. On the other hand, in LN of more than 10 mm in size, the in-field LN failure rate increase and the prognosis deteriorate. Therefore, a more aggressive treatment strategy is needed.
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Low-intensity, low-frequency ultrasound (LILFU) is the next-generation, non-invasive brain stimulation technology for treating various neurological and psychiatric disorders. However, the underlying cellular and molecular mechanism of LILFU-induced neuromodulation has remained unknown. Here, we report that LILFU-induced neuromodulation is initiated by opening of TRPA1 channels in astrocytes. The Ca2+ entry through TRPA1 causes a release of gliotransmitters including glutamate through Best1 channels in astrocytes. The released glutamate activates NMDA receptors in neighboring neurons to elicit action potential firing. Our results reveal an unprecedented mechanism of LILFU-induced neuromodulation, involving TRPA1 as a unique sensor for LILFU and glutamate-releasing Best1 as a mediator of glia-neuron interaction. These discoveries should prove to be useful for optimization of human brain stimulation and ultrasonogenetic manipulations of TRPA1.
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Astrócitos/metabolismo , Ácido Glutâmico/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Canal de Cátion TRPA1/genética , Ultrassonografia , Animais , Masculino , Camundongos , Distribuição Aleatória , Canal de Cátion TRPA1/metabolismoRESUMO
OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a fatal disease that shortens one's life expectancy and reduces the quality of life of patients. The current known treatments for COPD can only act to alleviate the symptoms. Recently, stem cells have demonstrated efficacy in various medical areas. The aim of this study was to investigate the possibility of using human Wharton's jelly-derived mesenchymal stem cells (MSC)s for lung recovery in a COPD mouse model. METHODS: Human Wharton's jelly was obtained during natural delivery or caesarean section from healthy women. Wharton's jelly-derived MSC was confirmed with expression of CD14, CD34, CD45, CD73, CD90, and CD105 using flow cytometry. Mice model (C57BL/6) of COPD were induced by injecting 10 µL elastase into the trachea and they were divided into three treatment groups (sham, vehicle, stem cell). The sham group was not induced COPD, nor provided any treatment; the vehicle group comprised of COPD-induced mice treated with normal saline; the stem cell group comprised of COPD-induced mice treated with Wharton's jelly-derived MSCs. The vehicle and mesenchymal stem cells (5 × 104 cells) were injected in tail vein 7 days following COPD induction. Mice were euthanized 7 days after vehicle and stem cell injection, and pathologic findings were confirmed. Mean Linear Intercept (MLI) was measured after emphysema-induced alveoli were identified. RESULTS: Cell surface markers were positive for CD105, CD90, and CD73 and negative for CD45, CD34, and CD14. Pathological tests showed that COPD-induced mice had significantly increased emphysema volume as compared with that in the sham group. The degree of emphysema in the stem cell group was reduced based on pathologic findings. The mean MLI of the sham group was measured as 38.85 ± 6.45. The mean MLI of the vehicle and stem cell groups were 163.05 ± 48.94 and 123.59 ± 30.53, respectively, and there was a statistically significant difference between the two groups (p = 0.008). CONCLUSIONS: Though the number of mice in the experiment was not large, human Wharton's jelly-derived MSCs showed pulmonary regenerative effects in the COPD mouse model. Although we cannot confirm the effects of Wharton's jelly-derived MSCs in COPD through this experiment, it can be used as a basis for a larger clinical experiment.
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The underlying mechanisms of how positive emotional valence (e.g., pleasure) causes preference of an associated context is poorly understood. Here, we show that activation of astrocytic µ-opioid receptor (MOR) drives conditioned place preference (CPP) by means of specific modulation of astrocytic MOR, an exemplar endogenous Gi protein-coupled receptor (Gi-GPCR), in the CA1 hippocampus. Long-term potentiation (LTP) induced by a subthreshold stimulation with the activation of astrocytic MOR at the Schaffer collateral pathway accounts for the memory acquisition to induce CPP. This astrocytic MOR-mediated LTP induction is dependent on astrocytic glutamate released upon activation of the astrocytic MOR and the consequent activation of the presynaptic mGluR1. The astrocytic MOR-dependent LTP and CPP were recapitulated by a chemogenetic activation of astrocyte-specifically expressed Gi-DREADD hM4Di. Our study reveals that the transduction of inhibitory Gi-signaling into augmented excitatory synaptic transmission through astrocytic glutamate is critical for the acquisition of contextual memory for CPP.
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Astrócitos/metabolismo , Região CA1 Hipocampal/metabolismo , Memória , Receptores Opioides mu/metabolismo , Animais , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/genética , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Camundongos , Camundongos Knockout , Receptores de Glutamato Metabotrópico/genética , Receptores de Glutamato Metabotrópico/metabolismo , Receptores Opioides mu/genéticaRESUMO
Ruthenium-quercetin conjugated nanoclusters (Ru-QC NCs) were synthesized via a one-pot reflux reaction. As inhalation of heavy metal ions like cobalt can lead to lung cancer, a fluorescent probe was designed for the determination of Co(II) both in aqueous solutions and living cells. The probe consists of hybrid nanoclusters with an average size of 2 nm that were prepared from ruthenium(II) ions and the flavonoid quercetin. These are termed as Ru-QC NCs. They display strong orange-colored emission with a peak at 558 nm under 465-nm excitation. The Ru-QC NCs are cell viable and enable imaging of cells and intracellular fluorometric detection of Co(II). The anticancer properties of Ru-QC NCs were screened by using non-small cell lung cancer (A549) and human dermal fibroblast (HDFa) cell lines. The Ru-QC NCs exert considerable cytotoxicity in A549 cells (at levels of 20-50 µg·mL-1), whereas no significant cytotoxicity was observed in case of HDFa cells. The anticancer properties of Ru-QC NCs were screened via MTT assay, live-dead staining, and ROS assay, respectively. Morphological changes of cancer cells were observed using atomic force microscopy. The fluorescent probe can detect Co(II) with a detection limit of 9.28 nM and with a linear response in the 0.03-100 µM concentration range. Graphical abstract Schematic representation of ruthenium-quercetin nanoclusters with potential anticancer properties. They are promising fluorescent probes for intracellular sensing of cobalt (Co2+) and bio-imaging. They exhibited efficient fluorometric detection of Co2+ with the limit of detection (LOD) of 9.28 nM.