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"This volume presents a broad yet detailed review of current knowledge of muscarinic receptors. It describes the detailed insights that have been obtained on the structure, function, and cell biology of muscarinic receptors. This volume also describes physiological analyses of muscarinic receptors and their roles in regulating the function of the brain and of a variety of peripheral tissues. This volume shows how the study of muscarinic receptors continues to provide new and surprising insights not just to the cholinergic system but to the broad areas of neurobiology, cell biology, pharmacology, and therapeutics."

"Proses invasi Plasmodium falciparum ke dalam sel darah merah merupakan tahapan penting pada infeksi malaria. Proses ini sangat kompleks melibatkan interaksi antara protein ligan pada permukaan merozoit parasit dengan reseptor permukaan pada sel darah merah inang. Reseptor sel darah merah yang digunakan pada saat invasi parasit P. falciparum diidentifikasi berdasarkan sensitivitasnya terhadap enzim neuraminidase (N), tripsin (T) dan kimotripsin (K). Penelitian ini dilakukan pada 69 darah pasien yang terinfeksi P. falciparum yang dikultur secara ex vivo secara langsung di laboratorium di Timika. Sel darah donor yang digunakan untuk uji invasi sebelumnya diberi perlakuan dengan 50 mU/ml neuraminidase, 1 mg/ml tripsin, atau 1 mg/ml kimotripsin. Kami mengidentifikasi 8 pola invasi parasit malaria dengan tipe terbanyak yang ditemukan adalah tipe A yang resistan terhadap ketiga perlakuan enzim (NrTrKr; 28,99%) dan tipe B (NsTsKr; 21,74%). Selain itu dilakukan pula analisis untuk mengetahui ekspresi relatif protein kelompok Duffy Binding Ligand (DBL) dan Reticulocytes Homolog (Rh) yang berperan pada proses invasi dengan mendeteksi ekspresi protein tersebut dari RNA yang disintesis menjadi cDNA yang diisolasi pada stadium schizon dari masing-masing isolat klinis. Protein kelompok DBL yang dianalisis adalah EBA-140, 175, 181 sedangkan dari kelompok Rh adalah Rh-1, 2a, dan 2b. Hasil analisis kuantitatif dengan real time reverse transcription PCR menunjukkan bahwa protein EBA-140, Rh-1 dan EBA-175 merupakan tiga protein ligan P. falciparum yang paling umum ditemukan pada isolat klinis parasit malaria di Timika, Papua. Variasi genetik sel darah merah seperti Southeast Asian Ovalocytosis (SAO), Gerbich negatif, dan varian hemoglobin (HbE) tidak ditemukan pengaruhnya pada proses invasi pada penelitian ini. Informasi yang dihasilkan pada penelitian ini diharapkan dapat menjadi masukkan untuk pengembangan vaksin malaria berbasis hambatan invasi parasit ke dalam sel darah merah.

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Plasmodium falciparum invasion is a complex process involving several parasite ligands and their receptors expressed on the red blood cell surface. We reported various receptors used by the parasite ligands during their invasion based on their sensitivity to neuraminidase (N), trypsin (T) or chymotrypsin (C). Most field isolates in Timika invaded red blood cells through type A receptor that was resistant to all enzyme treatments (NrTrCr; 28,99%) and type B that was sensitive to neuraminidase and trypsin (NsTsCr; 21,74%). The expression of two invasion ligands; Plasmodium falciparum Duffy binding ligand (PfDBL) and P. falciparum reticulocyte homolog (PfRh) were quantified from the schizonts stage of each isolate. We employed quantitative real-time reverse-transcription polymerase chain reaction (QRT-RT-PCR) to detect the expression of PfDBL family including EBA-140, EBA-175 and EBL-181 and PfRh genes such as Rh-1, Rh-2a, Rh-2b. We demonstrated thatEBA-140, Rh-1 and EBA-175 werethe major invasion ligands expressed in P. falciparum of Timikan isolates. The presence of red cell polymorphisms including the Southeast Asian Ovalocytosis (SAO), Gerbich negativity, and variant hemoglobin (HbE) as detected by PCR was not found to affect parasite invasion. The present study strengthens the support to include malaria invasion proteins into the development of malaria vaccine platform."

"Opening with a general introduction on chemokine function and chemokine receptor biology, the handbook goes on to cover the known implications of these signaling molecules in human diseases, such as cancer, neural disorders, and viral infection, including HIV/AIDS. The second half of the book systematically surveys current drug development efforts at targeting individual chemokine receptors, as well as other chemokine interaction partners. Contributions in the first part of the book are mainly from academia, whereas the second part contains up-to-date reports from the pharmaceutical industry."

"The book covers a broad spectrum of topics, ranging from pioneering research in the field of classical steroid hormones to very recently discovered orphan receptors and their modulators. State of the art technologies are also discussed in the individual chapters that help to develop a deeper insight into the biochemical and pharmacological principles underlying the biological function of nuclear receptors.Edited by two experts working at the pioneering pharmaceutical company and major global player in hormone-derived drugs, this handbook and reference systematically treats the drug development aspects of all human nuclear receptors, including recently characterized receptors such as PPAR, FXR and LXR. Authors from leading pharmaceutical companies around the world present examples and real-life data from their own work."

"ABSTRAKTelah dilakukan penelitian untuk mendapatkan ligan yang selektif dan berikatan kuat dengan reseptor estrogen melalui pengujian afinitas ikatan senyawa estradiol-17β-hemisuksinat. Untuk meningkatkan status senyawa tersebut menjadi kandidat senyawa aktif obat kanker payudara perlu diketahui selektifitasnya terhadap reseptor estrogen dengan metode Scintillation Proximity Assay (SPA). Reagen primer yang diperlukan dalam metode SPA adalah radioligan dan reseptor, dan dilakukan penandaan estradiol-17β-hemisuksinat dengan 125I sebagai radioligan. Studi ikatan radioligan dilakukan terhadap reseptor estrogen meggunakan sel MCF7. Penandaan dilakukan secara tidak langsung dengan dua tahap. Pertama dilakukan aktivasi estradiol-17β-hemisuksinat menggunakan isobutilkloroformat dan tributilamin sebagai katalis, dan penandaan histamin dengan 125I menggunakan metode kloramin-T. Tahap kedua adalah konjugasi histamin bertanda 125I dengan estradiol-17β-hemisuksinat yang sudah diaktivasi. Estradiol-17β-hemisuksinat bertanda 125I dilakukan ekstraksi menggunakan toluen dan fase organik dimurnikan dengan sistem KLT. Rendemen pemurnian yang diperoleh sebesar 79,8% untuk ekstraksi pelarut dan 84,4% untuk sistem KLT dengan kemurnian radiokimia 97,8%. Penentuan afinitas ikatan dilakukan dengan metode SPA menggunakan sel MCF7 yang mengekspresikan reseptor estrogen, dan diperoleh Kd sebesar 7,192 x 10-3 nM dan ikatan maksimum sebesar 336,1 nM. Afinitas ikatan estradiol-17β-hemisuksinat yang diperoleh tinggi, ditunjukkan dengan nilai Kd yang rendah.

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ABSTRACTResearch was carried out to get drugs that selective ligand and strongly bind estrogen receptors to determine the binding affinity to estradiol-17β-hemisuccinate. To improve the status of these compounds as a candidate for breast cancer active compound, selectivity of these compounds for estrogen receptor was studied using Scintillation Proximity Assay (SPA) method. Primary reagents required in the SPA method was radioligand and receptors, then performed with 125I labeling of estradiol-17β-hemisuccinate as a radioligand.

Radioligand binding studies were performed on MCF7 cell for estrogen receptor. The labeling process was performed by indirect method via two-stage reaction. First activation of estradiol-17β-hemisuccinate using isobutylchloroformate and tributylamine as a catalist, and labeling of histamine was carried out by 125I using Chloramin-T method. The second stage was conjugation of activated estradiol-17β-hemisuccinate with 125I-histamine. The estradiol-17β-hemisuccinate labeled with 125I was extracted using toluene and organic phase was purified by TLC system. The obtained purification yield for the extraction solvent was 79.8% and for the TLC system was 84,4% with a radiochemical purity was 97.8%. Determination of binding affinity by the SPA method using MCF7 cell lines which express estrogen receptors, were Kd of 7.192 x 10-3 nM and maximum binding of 336.1 nM. Having obtained binding affinity of estradiol-17β-hemisuccinate was obtained high, indicated by a low Kd values."

"This book gives an updated and expert overview of nuclear hormone receptors in drug metabolism and drug development and equips you with the interdisciplinary understanding of these receptors and how they can be regulated. Pharmaceutical researchers will find this extremely useful in developing drugs for cancer, heart disease, and diabetes treatment. This comprehensive resource collects scattered materials into one handy, informative volume."

"Terapi kortikosteroid pada pasien COVID-19 dimediasi oleh efek supresifnya terhadap regulasi respons inflamasi. Namun, hasilnya seringkali tidak dapat diprediksi. Penelitian ini bertujuan untuk mengeksplorasi prediktor respons kortikosteroid pada pasien COVID-19 derajat sedang-berat. Penelitian ini dibagi dalam 2 tahap, tahap pertama merupakan studi kohort retrospektif yang melibatkan 244 pasien dan tahap kedua merupakan studi cross-sectional terhadap 34 pasien yang spesimen biologisnya tersimpan di RS pada awal dan hari kelima terapi kortikosteroid. Penelitian dilakukan pada bulan Oktober 2021 hingga Oktober 2022 di RSUP dr. M.Djamil, Laboratorium Pusat Diagnostik dan Riset Penyakit Infeksi FK UNAND, dan Laboratorium Kesehatan Daerah Provinsi Jawa Barat. Peneliti menganalisis berbagai variabel klinis (usia, derajat ARDS, riwayat penggunaan steroid, adanya diabetes, hipertensi, gangguan fungsi ginjal) dan laboratorium (rasio neutrofil-limfosit, kadar feritin dan D-dimer) dengan respons terhadap terapi kortikosteroid pada tahap pertama. Pada tahap kedua dilakukan penelusuran peran reseptor glukokortikoid (GR) berupa tingkat ekspresi, variasi isoform, dan mutasi ekson dengan respons klinis terhadap kortikosteroid. Ekspresi GR, isoform, dan mutasi dianalisis dengan RNA-sekuensing leukosit. Selain itu, hubungan ekspresi GR dan ekspresi IκBα dan glucocorticoid-induced leucine zipper protein (GILZ) sebagai jalur steroid juga dievaluasi. Pasien diklasifikasikan menjadi kelompok responsif dan tidak responsif berdasarkan perbaikan status klinis dan kebutuhan oksigen. Pada analisis multivariat terlihat bahwa kadar feritin dapat memprediksi respons terhadap terapi kortikosteroid (OR 2,95 [95% CI 1,33−6,53]). Kelompok responsif memiliki ekspresi GR, IκBα dan GILZ lebih tinggi pada awal dan hari kelima pemberian kortikosteroid dibandingkan pasien tidak responsif. Varian atau mutasi isoform GR tidak berkorelasi dengan respons klinis. Berdasarkan temuan tersebut disarankan bahwa kadar feritin dapat memprediksi respons steroid pada pasien COVID-19, namun perlu ditelusuri prediktor independen lainnya. Ekspresi GR, IκBα dan GILZ kemungkinan berkaitan dengan respons terapi terhadap kortikosteroid pada pasien COVID-19.

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The effect of corticosteroid therapy in COVID-19 patients is mediated by its suppressive effect on the regulations of inflammatory response. However, its clinical outcome is often unpredictable. This study aimed to explore the predictors of corticosteroid response in Moderate-Severe COVID-19 patients. This research was conducted in 2 stages, the first stage was a retrospective cohort study involving 244 moderate-severe COVID-19 patients and the second stage was a cross-sectional study of 34 COVID-19 patients whose biological specimens were stored in the hospital at the baseline and fifth days of corticosteroid therapy. The research was conducted from October 2021 to October 2022 at Dr. M.Djamil General Hospital, Laboratory of Diagnostic and Research Center for Infectious Diseases Faculty of Medicine, Universitas Andalas, and Regional Health Laboratory of West Java Province. In the first stage, a multivariate analysis was conducted between various clinical (age, degree of ARDS, history of steroid use, presence of diabetes, hypertension, impaired renal function) and laboratory variables (neutrophil-lymphocyte ratio, ferritin and D-dimer levels) with response to corticosteroid therapy. In the second stage, we attempted to explore the role of the glucocorticoid receptor (GR), such as the expression, the variation of GR isoform, and the mutations of GR exon with clinical response to corticosteroids. GR expression, isoform, and mutation were determined by RNA sequencing from white blood cells. In addition, the relationship between GR expression and the expression of IκBα and glucocorticoid-induced leucine zipper protein (GILZ) as steroid pathways was also evaluated. Based on the improvement of clinical and oxygen status, patients were classified into responder and non-responder groups. Our findings indicate that ferritin levels can predict response to corticosteroid therapy (OR 2.95 [95% CI 1.336.53]). The responder group had higher GR, IκBα dan GILZ expression at baseline and after five days of corticosteroid treatment than non-responsder group. The GR isoform variant or mutation did not correlate with clinical response. Based on this finding, we suggest that ferritin levels in covid-19 patients could predict steroid response. This study also shows that the expression of GR, IκBα and GILZ may be related to the therapeutic response to corticosteroids in COVID-19 patients."