Reviews of Physiology, Biochemistry and Pharmacology (Reviews of Physiology, Biochemistry and Pharmacology, 179)

Leading researchers are specially invited to provide a complete understanding of a key topic within the multidisciplinary fields of physiology, biochemistry and pharmacology. In a form immediately useful to scientists, this periodical aims to filter, highlight and review the latest developments in these rapidly advancing fields.​ Acknowledgements Contents Immunomodulatory Effects of Curcumin in Rheumatoid Arthritis: Evidence from Molecular Mechanisms to Clinical Outcomes 1 Introduction 2 Curcumin: Molecular Mechanisms of Immunomodulatory Effects 3 Immunopathogenesis of RA 3.1 Role of Pro-Inflammatory Cytokines in the Pathogenesis of RA 3.2 Role of TH1 Cells in the Pathogenesis of RA 3.3 Role of TH17 Cells in the Pathogenesis of RA 3.4 Role of Treg Cells in the Pathogenesis of RA 3.5 Role of B Cells in the Pathogenesis of RA 4 Overview of Curcumin ́s Immunomodulatory Effects 4.1 Modulatory Effects of Curcumin on the Production of Pro-Inflammatory Cytokines 4.2 Modulatory Effects of Curcumin on TH1 Cells Differentiation and Function 4.3 Modulatory Effects of Curcumin on TH17 Cells Differentiation and Function 4.4 Modulatory Effects of Curcumin on Treg Cells Differentiation and Function 4.5 Modulatory Effects of Curcumin on B Cell Differentiation and Function 5 Clinical Efficacy and Immunomodulatory Effects of Curcumin in Human Studies 6 Conclusion References Potential of Renin-Angiotensin-Aldosterone System Modulations in Diabetic Kidney Disease: Old Players to New Hope! 1 Introduction 2 The Renin-Angiotensin-Aldosterone System 3 The Pressor Arm of RAAS 3.1 Renin 3.2 Angiotensin-Converting Enzyme 3.3 Angiotensin II 3.4 Ang II Type 1 Receptor 4 The Pressor RAAS Inhibitors in DKD: The Old Players 4.1 Direct Renin Inhibitors 4.2 ACE Inhibitors 4.3 AT1 Receptor Blockers 4.4 Mineralocorticoid Receptor Antagonists 4.5 ACEi and ARB Combination Therapy 4.6 ARB or ACEi with Renin Inhibition 4.7 Hurdles for RAAS Inhibition in DKD 5 The Depressor Arm of RAAS 5.1 Angiotensin-Converting Enzyme 2: Nature ́s ACEi 5.2 Angiotensin-(1-7) 5.3 Angiotensin II Type 2 Receptor 5.4 Mas Receptors 6 Modulation of the Depressor Arm of RAAS in DKD: A Better Alternative 6.1 ACE2 Activation 6.2 Ang-(1-7) Therapy 6.3 AT2 Receptor Modulations 6.4 Mas Receptor Modulations 7 Neprilysin Inhibition as Add-On to RAAS Blockage 7.1 Vasopeptidase Inhibitor (Dual ACEi/NEPi) 7.2 Angiotensin Receptor Neprilysin Inhibitors (ARNi) 8 Novel Combination Therapies (Fig. 4) 8.1 Simultaneous AT1 Receptor Inhibition and AT2 Receptor Activation 8.2 Add-On Therapy of Ang-(1-7) with RAAS Inhibitors 8.3 Dual AT2 Receptor and ACE2 Activation 8.4 Mas Receptor Agonist and DRI Combination Therapies 8.5 Concurrent Renin and Neprilysin Inhibition 8.6 Add-On Therapy of NEPi with ACE2 Activation 8.7 Dual pGC-A and Mas Receptor Activators 9 Conclusion and Perspective References Cross-Talk Between the Adenylyl Cyclase/cAMP Pathway and Ca2+ Homeostasis 1 Adenylyl Cyclases: Overview 1.1 Adenylyl Cyclases and Cancer 2 Regulation of ACs by Ca2+ 2.1 Store-Operated Calcium Entry-Dependent AC Activation 2.1.1 Store-Operated Calcium Entry 2.1.2 Regulation of Adenylyl Cyclases by Store-Operated Calcium Entry 2.2 STIM1-Dependent AC Activation 2.3 Ca2+-Dependent AC Inactivation 2.4 AC Regulation by Ca2+-Dependent Enzymes: PKCs, CMKs, and CaN 3 Regulation of Ca2+ Homeostasis by cAMP Signaling 4 Regulation of Store-Operated Calcium Entry by Adenylyl Cyclases 4.1 Regulation of Orai1 Function by AC8 4.2 Remodeling of the Regulation of Orai1 by AC8 in Cancer Cells References Developmental Changes in Phosphate Homeostasis 1 Introduction 1.1 Transcellular Intestinal Phosphate Absorption/Renal Phosphate Reabsorption 1.2 Paracellular Phosphate Flux 2 Ontogeny of Intestinal Phosphate Absorption 3 Ontogeny of Renal Phosphate Handling 4 Ontogeny of Hormonal Factors Directing Intestinal and Renal Phosphate Handling 5 A Proposed General Model: Intestinal and Renal Ontogeny of Phosphate Handling 6 Inorganic Phosphate: Its High Consumption in the Western World and Potential Ramifications for the Infant 7 Future Research 8 Conclusions References Ligands and Signaling of Mas-Related G Protein-Coupled Receptor-X2 in Mast Cell Activation 1 Introduction 2 mMrgprB2 and rMrgprB3 as Orthologs of Human MRGPRX2 3 Physiological and Pathological Functions of MRGPRX2 in Human MCs 4 Signaling Pathways and Regulation of MRGPRX2 in Activation of MCs 4.1 MRGPRX2-Mediated MCs Degranulation and Generation of Cytokines/Chemokines 4.2 Binding Sites of Ligands on MRGPRX2 4.3 Activation of MRGPRX2 in MCs Via the Gαi and Gαq Families 4.4 Signaling of Ca2+ in MRGPRX2-Mediated Activation of MCs 4.5 MAPK and NF-κB Pathways in MRGPRX2-Mediated MCs Activation 5 Agonists 5.1 Peptides 5.1.1 Antimicrobial Peptides β-Defensins and Analogs θ-Defensin Analogs LL-37 and LL-37-Derived Peptides AG-30/5C AMPs-Derived from Insulin-Like Growth Factor-Binding Protein 5 Magainin-2 Indolicidin Catestatin Small-Molecule Nonpeptide Host-Defense Peptides Polymyxins 5.1.2 Neuropeptides Substance P Pituitary Adenylate Cyclase-Activating Peptides Somatostatin and Its Analogues 5.1.3 Peptide Hormones Pro-adrenomedullin Peptides Vasoactive Intestinal Peptide Cetrorelix Leuprolide Sermorelin Octreotide Kallidin 5.1.4 Mast Cell Degranulating Peptides Mast Cell Degranulating Peptide Granuliberin R Mastoparan 5.1.5 Other Endogenous Protein Fragments CNP (1-17) and Tropomyosin (1-12) Human Serum Albumin Sequences Platelet Factor-4 Hemokinin-1 5.2 Nonpeptides 5.2.1 Compound 48/80 5.2.2 Neuromuscular Blocking Agents 5.2.3 Fluoroquinolone Antibiotics 5.2.4 Opioid Drugs 5.2.5 Herbal Extracts Sinomenine Complanadine A 5.2.6 Other Drugs Icatibant Iopamidol 5.2.7 MRGPRX2-Selective Ligands from a Compound Library 6 Inhibitors 6.1 GPCR Inhibitors 6.1.1 Pertussis Toxin 6.1.2 NK-1R Antagonists 6.2 Cytokines 6.2.1 Interleukin-33 6.2.2 Stem Cell Factor 6.3 Herbal Extracts 6.3.1 Saikosaponin A 6.3.2 Resveratrol 6.3.3 Quercetin 6.3.4 Osthole 6.3.5 Genistein 6.3.6 Shikonin 6.3.7 Piperine 6.3.8 Paeoniflorin 6.4 Small-Molecule MRGPRX2 Antagonists 6.5 MRGPRX2-Targeting Antagonistic DNA Aptamer 7 Balanced and Biased Ligands of MRGPRX2 8 Summary References Single-Cell Sequencing and Organoids: A Powerful Combination for Modelling Organ Development and Diseases 1 Introduction 2 Single-Cell Sequencing 2.1 Definition 2.2 The Advantage of scRNA-Seq 2.3 The Critical Steps of scRNA-Seq 2.3.1 Capturing Single Cells 2.3.2 From Single Cells to a cDNA Library PCR-Based Amplification T7-Based In Vitro Transcription (IVT) Amplification Rolling Circle Amplification 3 Organoids 4 The Combination of scRNA-Seq and Organoid Model Development, Regeneration and Diseases 4.1 Discovery of Rare/Novel Cell Types and Gene Markers 4.2 Recapitulation of the Cellular Heterogeneity of Bodily Organs 4.3 Delineation of Cell Differentiation Pathways 4.4 Identification of Gene Expression Variability at the Single-Cell Level 4.5 Modelling Diseases 5 Limitations of Organoid Models 6 Conclusions and Perspectives References Immunomodulatory Effects of Curcumin in Rheumatoid Arthritis: Evidence from Molecular Mechanisms to Clinical Outcomes Saeed Mohammadian Haftcheshmeh, Arezou Khosrojerdi, Ali Aliabadi, Shadi Lotfi, Asadollah Mohammadi, and Amir Abbas Momtazi-Borojeni Potential of Renin-Angiotensin-Aldosterone System Modulations in Diabetic Kidney Disease: Old Players to New Hope! Vajir Malek, Sachin V. Suryavanshi, Nisha Sharma, Yogesh A. Kulkarni, Shrikant R. Mulay, and Anil Bhanudas Gaikwad Cross-Talk Between the Adenylyl Cyclase/cAMP Pathway and Ca2+ Homeostasis Jose Sanchez-Collado, Jose J. Lopez, Isaac Jardin, Gines M. Salido, and Juan A. Rosado Developmental Changes in Phosphate Homeostasis Tate MacDonald, Matthew Saurette, Megan R. Beggs, and R. Todd Alexander Ligands and Signaling of Mas-Related G Protein-Coupled Receptor-X2 in Mast Cell Activation Yan-Ni Mi, Na-Na Ping, and Yong-Xiao Cao Single-Cell Sequencing and Organoids: A Powerful Combination for Modelling Organ Development and Diseases Yuebang Yin, Peng-Yu Liu, Ping Li, Yinghua Shi