Role of mitophagy in pulmonary hypertension: Targeting the mechanism and pharmacological intervention.

Mitophagy, a crucial pathway in eukaryotic cells, selectively eliminates dysfunctional mitochondria, thereby maintaining cellular homeostasis via mitochondrial quality control. Pulmonary hypertension (PH) refers to a pathological condition where pulmonary arterial pressure is abnormally elevated due to various reasons, and the underlying pathogenesis remains elusive. This article examines the molecular mechanisms underlying mitophagy, emphasizing its role in PH and the progress in elucidating related molecular signaling pathways. Additionally, it highlights current drug regulatory pathways, aiming to provide novel insights into the prevention and treatment of pulmonary hypertension.

Expression and regulation of HIF-1a in hypoxic pulmonary hypertension: Focus on pathological mechanism and Pharmacological Treatment.

Hypoxia inducible factor-1(HIF-1), a heterodimeric transcription factor, is composed of two subunits (HIF-1α and HIF-1ß). It is considered as an important transcription factor for regulating oxygen changes in hypoxic environment, which can regulate the expression of various hypoxia-related target genes and play a role in acute and chronic hypoxia pulmonary vascular reactions. In this paper, the function and mechanism of HIF-1a expression and regulation in hypoxic pulmonary hypertension (HPH) were reviewed, and current candidate schemes for treating pulmonary hypertension by using HIF-1a as the target were introduced, so as to provide reference for studying the pathogenesis of HPH and screening effective treatment methods.

Celastrol: The new dawn in the treatment of vascular remodeling diseases.

Evidence is mounting that abnormal vascular remodeling leads to many cardiovascular diseases (CVDs). This suggests that vascular remodeling can be a crucial target for the prevention and treatment of CVDs. Recently, celastrol, an active ingredient of the broadly used Chinese herb Tripterygium wilfordii Hook F, has attracted extensive interest for its proven potential to improve vascular remodeling. Substantial evidence has shown that celastrol improves vascular remodeling by ameliorating inflammation, hyperproliferation, and migration of vascular smooth muscle cells, vascular calcification, endothelial dysfunction, extracellular matrix remodeling, and angiogenesis. Moreover, numerous reports have proven the positive effects of celastrol and its therapeutic promise in treating vascular remodeling diseases such as hypertension, atherosclerosis, and pulmonary artery hypertension. The present review summarizes and discusses the molecular mechanism of celastrol regulating vascular remodeling and provides preclinical proof for future clinical applications of celastrol.

Transformation from polycythemia vera to acute promyelocytic leukemia: Case report and literature review.

INTRODUCTION: Transformation from chronic myeloproliferative neoplasm to acute leukemia is a feature of myeloproliferative neoplasm; however, the rate is not high. Transformation to acute promyelocytic leukemia is rare. Here, we report a case of transformation of polycythemia vera to acute promyelocytic leukemia and describe a process of clonal evolution that has not yet been reported. PATIENT CONCERNS: In this case, a 51-year-old woman was diagnosed with polycythemia vera and concomitant JAK2/V617F mutations in July 2019. She underwent intermittent phlebotomy and oral hydroxyurea irregularly. After 2 years, the patient complained of fatigue and poor sleep quality for 2 months. DIAGNOSIS: Further examination revealed marked hypercellularity and grade 1 bone marrow fibrosis with the PML/RARαV variant (23.85% mutation load), WT1-Exon1 (37.8%), WT1-Exon9 (4.1%), JAK3-Exon7 (49.3%), and RELN-Exon55 (45.8%). According to the World Health Organization classification of tumors of hematopoietic and lymphoid tissues, the patient was ultimately diagnosed with a rare transformation of polycythemia vera to acute promyelocytic leukemia. INTERVENTIONS: The patient underwent dual induction therapy with all-trans-retinoic acid and arsenic trioxide. OUTCOMES: After 28 days of induction therapy, the patient achieved complete remission, was compliant and the treatment was well tolerated. CONCLUSION: Polycythemia vera can transform into acute promyelocytic leukemia; therefore, it is important to review bone aspiration and other tests to perform a comprehensive assessment and monitor the disease status, to detect disease progression and intervene early when it transforms into acute promyelocytic leukemia.

Gemfibrozil has antidepressant effects in mice: Involvement of the hippocampal brain-derived neurotrophic factor system.

Major depressive disorder has become one of the most serious neuropsychiatric disorders worldwide. However, currently available antidepressants used in clinical practice are ineffective for a substantial proportion of patients and always have side effects. Besides being a lipid-regulating agent, gemfibrozil is an agonist of peroxisome proliferator-activated receptor-α (PPAR-α). We investigated the antidepressant effects of gemfibrozil on C57BL/6J mice using the forced swim test (FST) and tail suspension test (TST), as well as the chronic unpredictable mild stress (CUMS) model of depression. The changes in brain-derived neurotrophic factor (BDNF) signaling cascade in the brain after CUMS and gemfibrozil treatment were further assessed. Pharmacological inhibitors and lentivirus-expressed short hairpin RNA (shRNA) were also used to clarify the antidepressant mechanisms of gemfibrozil. Gemfibrozil exhibited significant antidepressant actions in the FST and TST without affecting the locomotor activity of mice. Chronic gemfibrozil administration fully reversed CUMS-induced depressive-like behaviors in the FST, TST and sucrose preference test. Gemfibrozil treatment also restored CUMS-induced inhibition of the hippocampal BDNF signaling pathway. Blocking PPAR-α and BDNF but not the serotonergic system abolished the antidepressant effects of gemfibrozil on mice. Gemfibrozil produced antidepressant effects in mice by promoting the hippocampal BDNF system.

An organocatalytic asymmetric sequential allylic alkylation-cyclization of Morita-Baylis-Hillman carbonates and 3-hydroxyoxindoles.

The first organocatalytic asymmetric sequential allylic alkylation-cyclization of Morita-Baylis-Hillman carbonates and 3-hydroxyoxindoles has been developed to afford spirooxindoles bearing α-methylene-γ-butyrolactone motifs in 25-85% yield, 60-94% ee and up to >20 : 1 diastereoselectivity.

Highly enantioselective aldol reaction of acetone with ß,γ-unsaturated α-keto esters promoted by simple chiral primary-tertiary diamine catalysts.

A series of primary-tertiary diamine catalysts were successfully applied to promote the enantioselective aldol reaction of acetone with ß,γ-unsaturated α-keto esters in excellent yields (up to 99%) and enantioselectivities (up to 96% ee).

Enantioselective α-amination of branched aldehydes promoted by simple chiral primary amino acids.

A series of simple chiral primary amino acids were first successfully applied to promote the enantioselective α-amination of branched aldehydes with azadicarboxylates and the desired adducts bearing quaternary stereogenic centers were obtained in excellent yields (up to 99%) and enantioselectivities (up to 97% ee).