Serum thyroid hormone antibodies are frequent in patients with polyglandular autoimmune syndrome type 3, particularly in those who require thyroxine treatment

Polyglandular autoimmune syndrome (PAS) type 3 consists of autoimmune thyroid disease (AITD) coexisting with ≥1 non-thyroidal autoimmune disease (NTAID) other than Addison’s disease and hypoparathyroidism. We evaluated the prevalence and repertoire of thyroid hormones antibodies (THAb) in PAS-3 patients. Using a radioimmunoprecipation technique, we measured THAb (T3IgM, T3IgG, T4IgM, and T4IgG) in 107 PAS-3 patients and 88 controls (patients with AITD without any NTAID). Based on the selective coexistence of AITD with one NTAID (chronic autoimmune gastritis, non-segmental vitiligo or celiac disease), patients were divided into group 1 (chronic autoimmune gastritis positive, n = 64), group 2 (non-segmental vitiligo positive, n = 24), and group 3 (celiac disease positive, n = 15). At least one of the four THAb was detected in 45 PAS-3 patients (42.1%) and 28 controls (31.8%, P = 0.14), with similar rates in the three PAS-3 groups. The rates of T3Ab, T4Ab, and T3 + T4Ab were similar in groups 1 and 2, while in group 3, T3Ab was undetected (P = 0.02). In PAS-3 patients, the rate of levothyroxine treatment was greater in THAb-positive patients compared to THAb-negative patients (76.7 vs. 56.1%, P = 0.03, RR = 1.4, 95% CI 1.03–1.81). Not unexpectedly, levothyroxine daily dose was significantly higher in group 1 and group 3, namely in patients with gastrointestinal disorders, compared to group 2 (1.9 ± 0.4 and 1.8 ± 0.3 vs. 1.5 ± 0.2 μg/kg body weight, P = 0.0005 and P = 0.004). Almost half of PAS-3 patients have THAb, whose repertoire is similar if chronic autoimmune gastritis or celiac disease is present. A prospective study would confirm whether THAb positivity predicts greater likelihood of requiring levothyroxine treatment

Mir-34a-5p Mediates Cross-Talk between M2 Muscarinic Receptors and Notch-1/EGFR Pathways in U87MG Glioblastoma Cells: Implication in Cell Proliferation

Glioblastoma (GBM) is the most aggressive human brain tumor. The high growth potential and decreased susceptibility to apoptosis of the glioma cells is mainly dependent on genetic amplifications or mutations of oncogenic or pro-apoptotic genes, respectively. We have previously shown that the activation of the M2 acetylcholine muscarinic receptors inhibited cell proliferation and induced apoptosis in two GBM cell lines and cancer stem cells. The aim of this study was to delve into the molecular mechanisms underlying the M2-mediated cell proliferation arrest. Exploiting U87MG and U251MG cell lines as model systems, we evaluated the ability of M2 receptors to interfere with Notch-1 and EGFR pathways, whose activation promotes GBM proliferation. We demonstrated that the activation of M2 receptors, by agonist treatment, counteracted Notch and EGFR signaling, through different regulatory cascades depending, at least in part, on p53 status. Only in U87MG cells, which mimic p53-wild type GBMs, did M2 activation trigger a molecular circuitry involving p53, Notch-1, and the tumor suppressor mir-34a-5p. This regulatory module negatively controls Notch-1, which affects cell proliferation mainly through the Notch-1/EGFR axis. Our data highlighted, for the first time, a molecular circuitry that is deregulated in the p53 wild type GBM, based on the cross-talk between M2 receptor and the Notch-1/EGFR pathways, mediated by mir-34a-5p

SUSTAINABILITY EVALUATION OF DEWARUCI UNDERPASS INTERSECTIONS

Abstract Indonesian commitment to sustainable development needs to be supported by real actions. Such as to organize sustainable road construction. The Ministry of Public Works Policy related to the field of road has been in line with the international agreement of sustainable development. However, to make sure that road projects have been implemented in sustainable way, a proper assessment of the sustainability measures is required. Dewa Ruci underpass road project was one of case study of sustainable road system rating. The procedure of the rating system is done by collecting the required documents comparing with the sustainable criteria of Green Road Rating System. Road projects in Indonesia have met the technical standards and some of the environmental requirements that have been issued by the Government. Dewa Ruci underpass projects including projects that have met the technical standards and environmental requirements. From the efforts of sustainable practices that have been performed, Dewa Ruci Underpass project was rated according to the rating system, and it reached the level of four stars. The criteria on the Green Roads still have to be disseminated to be known by those stakeholders, besides the need to disseminate the rating system. Thus road projects in Indonesia can be more sustainable. Implementation of sustainable road rating system in Indonesia needs to be supported by dissemination. Keywords: system rating, road sustainable, principle of sustainable road  Abstrak Komitmen Indonesia untuk pengembangan berkelanjutan diperlukan dukungan dengan aksi aksi yang nyata, seperti organisasi konstruksi jalan berkelanjutan. Kebijakan Kementerian Pekerjaan Umum terkait dengan sector jalan telah selaras dengan perjanjian internasional untuk pengembangan berkelanjutan. Walaupun demikian, untuk meyakini proyek proyek dikerjakan secara berkelanjutan, penilaian yang tepat untuk pengukuran keberlanjutan dibutuhkan. Proyek Underpass Dewa Ruci dipilih untuk kasus studi sistem peringkatan jalan berkelanjutan. Prosedur sistem peringkatan dilakukan dengan pengumpulan dokumen dokumen dan dibandingkan dengan Kriteria Sistem Peringkatan Jalan Hijau. Proyek jalan di Indonesia harus memenuhi standar teknis dan beberapa persyaratan lingkungan yang ditetapkan pemerintah termasuk Underpass Dewa Ruci. Ditinjau dari upaya keberlanjutan yang dihasilkan, Underpass Dewa Ruci telah dinilai sesuai dengan sistem peringkat jalan dan mencapai peringkat bintang empat. Kriteria jalan hijau perlu didesiminasikan kepada seluruh pemangku kepentingan, khususnya sistem peringkatannya. Lebih lanjut, proyek proyek jalan di Indonesia akan dapat lebih berkelanjutan. Implementasi peringkatan jalan berkeselamatan perlu didukung dengan upaya-upaya diseminasi. Kata-kata kunci: sistem peringkatan, jalan berkelanjutan, prinsip prinsip jalan berkelanjutan

SUSTAINABILITY EVALUATION OF DEWARUCI UNDERPASS INTERSECTIONS

Abstract Indonesian commitment to sustainable development needs to be supported by real actions. Such as to organize sustainable road construction. The Ministry of Public Works Policy related to the field of road has been in line with the international agreement of sustainable development. However, to make sure that road projects have been implemented in sustainable way, a proper assessment of the sustainability measures is required. Dewa Ruci underpass road project was one of case study of sustainable road system rating. The procedure of the rating system is done by collecting the required documents comparing with the sustainable criteria of Green Road Rating System. Road projects in Indonesia have met the technical standards and some of the environmental requirements that have been issued by the Government. Dewa Ruci underpass projects including projects that have met the technical standards and environmental requirements. From the efforts of sustainable practices that have been performed, Dewa Ruci Underpass project was rated according to the rating system, and it reached the level of four stars. The criteria on the Green Roads still have to be disseminated to be known by those stakeholders, besides the need to disseminate the rating system. Thus road projects in Indonesia can be more sustainable. Implementation of sustainable road rating system in Indonesia needs to be supported by dissemination. Keywords: system rating, road sustainable, principle of sustainable road  Abstrak Komitmen Indonesia untuk pengembangan berkelanjutan diperlukan dukungan dengan aksi aksi yang nyata, seperti organisasi konstruksi jalan berkelanjutan. Kebijakan Kementerian Pekerjaan Umum terkait dengan sector jalan telah selaras dengan perjanjian internasional untuk pengembangan berkelanjutan. Walaupun demikian, untuk meyakini proyek proyek dikerjakan secara berkelanjutan, penilaian yang tepat untuk pengukuran keberlanjutan dibutuhkan. Proyek Underpass Dewa Ruci dipilih untuk kasus studi sistem peringkatan jalan berkelanjutan. Prosedur sistem peringkatan dilakukan dengan pengumpulan dokumen dokumen dan dibandingkan dengan Kriteria Sistem Peringkatan Jalan Hijau. Proyek jalan di Indonesia harus memenuhi standar teknis dan beberapa persyaratan lingkungan yang ditetapkan pemerintah termasuk Underpass Dewa Ruci. Ditinjau dari upaya keberlanjutan yang dihasilkan, Underpass Dewa Ruci telah dinilai sesuai dengan sistem peringkat jalan dan mencapai peringkat bintang empat. Kriteria jalan hijau perlu didesiminasikan kepada seluruh pemangku kepentingan, khususnya sistem peringkatannya. Lebih lanjut, proyek proyek jalan di Indonesia akan dapat lebih berkelanjutan. Implementasi peringkatan jalan berkeselamatan perlu didukung dengan upaya-upaya diseminasi. Kata-kata kunci: sistem peringkatan, jalan berkelanjutan, prinsip prinsip jalan berkelanjutan

Dysregulated homeostasis of acetylcholine levels in immune cells of RR-multiple sclerosis patients

Multiple sclerosis (MS) is characterized by pro-inflammatory cytokine production. Acetylcholine (ACh) contributes to the modulation of central and peripheral inflammation. We studied the homeostasis of the cholinergic system in relation to cytokine levels in immune cells and sera of relapsing remitting-MS (RR-MS) patients. We demonstrated that lower ACh levels in serum of RR-MS patients were inversely correlated with the increased activity of the hydrolyzing enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Interestingly, the expression of the ACh biosynthetic enzyme and the protein carriers involved in non-vesicular ACh release were found overexpressed in peripheral blood mononuclear cells of MS patients. The inflammatory state of the MS patients was confirmed by increased levels of TNF alpha, IL-12/IL-23p40, IL-18. The lower circulating ACh levels in sera of MS patients are dependent on the higher activity of cholinergic hydrolyzing enzymes. The smaller ratio of ACh to TNF alpha, IL-12/IL-23p40 and IL-18 in MS patients, with respect to healthy donors (HD), is indicative of an inflammatory environment probably related to the alteration of cholinergic system homeostasis

Butyrylcholinesterase and Acetylcholinesterase polymorphisms in Multiple Sclerosis patients: Implication in peripheral inflammation

Multiple Sclerosis (MS) is an autoimmune disease, having not fully understood aetiology, and both genetic and environmental factors contribute to the pathogenesis of the disease. The cholinergic system has been indicated as a mediator of neuro-immune interactions, as well as an internal regulator of immune responses. The aim of the present research was to assess the associations between BChE and AChE genetic variations and serum cholinergic and inflammatory profiles in 102 Relapsing Remitting-MS patients and 117 healthy controls. An increased frequency of the BChE K-allele in MS patients as compared to controls was found. In addition, data showed that patients had higher BChE enzymatic activity, which is increased by the presence of the polymorphic allele and reduced amounts of circulating ACh. AChE polymorphism was significantly associated to reduced activity in both patients and controls. We propose that serum BChE and AChE activity may be used as a secondary markers to assess the role of non-neuronal cholinergic system in regulating peripheral inflammation via ACh regulation. This pilot study shed light on the role of the non-neuronal cholinergic system in immune cells to better understand MS pathogenesis. The cross-talk between the periphery and the CNS could have a new undescribed crucial role for MS, regarded as a systemic disease