Molecular basis of lipid and ligand regulation of prostaglandin receptor DP2.

Prostaglandin D2 receptor 2 (DP2) is an important anti-inflammatory and antiallergic drug target. While inactive DP2 structures are known, its activation mechanisms and biased signaling remain unclear. Here, we report cryo-EM structures of an apo DP2-Gi complex, a DP2-Gi complex bound to the endogenous ligand Prostaglandin D (PGD), and a DP2-Gi complex bound to indomethacin, an arrestin-biased ligand, at resolutions of 2.

Molecular recognition and activation of the prostacyclin receptor by anti-pulmonary arterial hypertension drugs.

The prostacyclin (PGI) receptor (IP) is a G-coupled receptor associated with blood pressure regulation, allergy, and inflammatory response. It is a main therapeutic target for pulmonary arterial hypertension (PAH) and several other diseases. Here we report cryo-electron microscopy (cryo-EM) structures of the human IP-G complex bound with two anti-PAH drugs, treprostinil and MRE-269 (active form of selexipag), at global resolutions of 2.

Immunopathogenesis and immunomodulatory therapy for myocarditis.

Myocarditis is an inflammatory cardiac disease characterized by the destruction of myocardial cells, infiltration of interstitial inflammatory cells, and fibrosis, and is becoming a major public health concern. The aetiology of myocarditis continues to broaden as new pathogens and drugs emerge. The relationship between immune checkpoint inhibitors, severe acute respiratory syndrome coronavirus 2, vaccines against coronavirus disease-2019, and myocarditis has attracted increased attention.

Splice-Altering Mutations in Marfan Syndrome: A Case Report and Literature Review.

Marfan syndrome (MFS) is a life-threatening autosomal dominant genetic disorder of connective tissue caused by the pathogenic mutation of FBN1. Whole exome sequencing and Sanger sequencing were performed to identify the pathogenic mutation. The transcriptional consequence of the splice-altering mutation was analyzed via minigene assays and reverse-transcription PCR.

insertion mutation causes cardiac-only Danon disease: A case report.

Danon disease is a rare disease caused by glycogen storage lysosomal disorder. It is related to the pathogenic mutation of the gene. In this case report, we present a patient with a novel pathogenic mutation (c.

A Modified Technique for Transverse Aortic Constriction in Mice.

Transverse aortic constriction (TAC) is a frequently used surgery in research regarding heart failure and cardiac hypertrophy based on the formation of pressure overload in mouse models. The main challenge of this procedure is to clearly visualize the transverse aortic arch and precisely band the target vessel. Classical approaches perform a partial thoracotomy to expose the transverse aortic arch.

Variant Angina is Associated with Myocarditis.

Background: Vasospastic angina (VSA) is caused by severe diffuse or segmental coronary artery spasms. Patients with variant angina have poor clinical outcomes, although nitrates and calcium blockers help improve patient symptoms because there is no understanding of the etiology and causal treatment. The present study investigated whether VSA is associated with inflammation of the heart.

Chlorpromazine Efficiently Treats the Crisis of Pheochromocytoma: Four Case Reports and Literature Review.

Pheochromocytoma multisystem crisis (PMC) is a potentially lethal emergency due to catecholamine secretion. The condition manifests as severe hypertension to intractable cardiogenic shock and has a high mortality rate. This study explored the efficacy and safety of applying chlorpromazine on PMC patients.

Good or bad: Application of RAAS inhibitors in COVID-19 patients with cardiovascular comorbidities.

The coronavirus disease 2019 (COVID-19) pandemic is caused by a newly emerged coronavirus (CoV) called Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). COVID-19 patients with cardiovascular disease (CVD) comorbidities have significantly increased morbidity and mortality. The use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor type 1 blockers (ARBs) improve CVD outcomes; however, there is concern that they may worsen the prognosis of CVD patients that become infected with SARS-CoV-2 because the virus uses the ACE2 receptor to bind to and subsequently infect host cells.

The coexistence of a novel WNK1 variant and a copy number variation causes hereditary sensory and autonomic neuropathy type IIA.

Background: Hereditary sensory and autonomic neuropathy (HSAN) type II is a group of extremely rare autosomal recessive neurological disorders with heterogeneous clinical and genetic characteristics.

Methods: We performed high-depth next-generation targeted sequencing using a custom-ordered "HSAN" panel, covering WNK1, NTRK1, NGF, SPTLC1 and IKBKAP genes, to identify pathogenic variants of the proband as well as the family members. We also performed whole exome sequencing to further investigate the potential occurrence of additional pathogenic variants in genes that were not covered by the "HSAN" panel.