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The metabolism of cells and blood circulation allow for the constant production and destruction of red blood cells. Erythrocyte formation allows red blood cells to regenerate, which is crucial for maintaining the equilibrium of the organism. Erythrocyte formation is a multi‐step, intricate process with distinct structural and functional characteristics at each stage. Erythropoiesis is regulated by a number of signaling pathways; malfunctional regulatory mechanisms may result in disease and aberrant erythropoiesis. Therefore, this article focuses on a review of the erythroid formation process, related signaling pathways, and red blood cell lineage diseases. [ABSTRACT FROM AUTHOR]

Objectives: Poor oocyte quality is detrimental to fertilization and embryo development, which causes infertility. Cystathionine β‐synthase (CBS) is one of the key enzymes modulating the metabolism of homocysteine (Hcy). Studies have shown that CBS plays an important role in female reproduction. However, the role of CBS in regulating oocyte quality during meiotic maturation still needs further investigation. Materials and Methods: Immunohistochemistry, immunofluorescence, drug treatment, western blot, cRNA construct and in vitro transcription, microinjection of morpholino oligo and cRNA were performed for this study. Results: We found that CBS was expressed both in human and mouse oocytes of follicles. In mouse oocytes, CBS was distributed in the nucleus at germinal vesicle (GV) stage and localized to spindle from germinal vesicle breakdown (GVBD) to metaphase II (MII). The expression of CBS was reduced in ovaries and oocytes of aged mice. CBS depletion resulted in meiotic arrest, spindle abnormality and chromosome misalignment, disrupted kinetochore‐microtubule attachments and provoked spindle assembly checkpoint (SAC). CBS was disassembled when microtubules were disrupted with nocodazole, and co‐localized with the stabilized microtubules after taxol treatment. Furthermore, CBS depletion decreased the acetylation of α‐tubulin. Conclusions: These results reveal that CBS is required for the acetylation of α‐tubulin to ensure proper spindle assembly in regulating oocyte quality during meiotic maturation. [ABSTRACT FROM AUTHOR]

Cardiomyocytes autophagy is essential for maintaining cardiac function. Our previous studies have found that β1‐adrenergic receptor autoantibody (β1‐AA) induced the decreased myocardial autophagic flux, which resulted in cardiomyocyte death and cardiac dysfunction. And other studies demonstrated that β1‐AA induced the decrease of AMPK phosphorylation, the key hub of autophagy pathway, while adiponectin up‐regulated autophagic flux mediated by AMPK. However, it is not clear whether adiponectin improves the inhibition of myocardial autophagic flux induced by β1‐AA by up‐regulating the level of AMPK phosphorylation. In this study, it has been confirmed that β1‐AA induced the decrease of AMPK phosphorylation level in both vivo and vitro. Moreover, pretreatment of cardiomyocytes with AMPK inhibitor Compound C could further reduce the autophagic flux induced by β1‐AA. Adiponectin deficiency could aggravate the decrease of myocardial AMPK phosphorylation level, autophagic flux and cardiac function induced by β1‐AA. Further, exogenous adiponectin could reverse the decline of AMPK phosphorylation level and autophagic flux induced by β1‐AA and even reduce cardiomyocyte death. While pretreated with the Compound C, the adiponectin treatment did not improve the decreased autophagosome formation, but still improved the decreased autophagosome clearance induced by β1‐AA in cardiomyocytes. This study is the first time to confirm that β1‐AA could inhibit myocardial autophagic flux by down‐regulating AMPK phosphorylation level. Adiponectin could improve the inhibition of myocardial autophagic flux induced by β1‐AA partly dependent on AMPK, so as to provide an experimental basis for the treatment of patients with β1‐AA‐positive cardiac dysfunction. [ABSTRACT FROM AUTHOR]

Cardiac dysfunction is involved in disorders of energy metabolism. High‐titre autoantibodies against the β1‐adrenoceptor (β1‐AAs) have been reported to exist in patients with cardiac dysfunction; however, the mechanism by which β1‐AAs affect cardiac function is unknown. This study aimed to determine whether β1‐AAs disturb myocardium energy metabolism and cause cardiac dysfunction. β1‐AA monoclonal antibodies (β1‐AAmAbs) were successfully pre‐synthesized by hybridoma clones and used in all experiments. β1‐AAmAbs impaired cardiac function and induced a myocardial metabolic disturbance, as evidenced by decreased left ventricular ejection fraction and fractional shortening. In addition, β1‐AAmAbs decreased the adenosine triphosphate level and increased cardiac energy consumption (rate–pressure product). We further showed that the effects of β1‐AAmAbs on heart tissue might involve the mitochondria and metabolic pathways via the β1‐adrenoceptor based on an immunoprecipitation and mass spectrometry. Additionally, we found that β1‐AAmAbs impaired myocardial mitochondrial structure, decreased the membrane potential, and induced insufficient mitophagy. In conclusion, β1‐AAmAb‐induced cardiac dysfunction is partly due to a disturbance in myocardial energy metabolism. [ABSTRACT FROM AUTHOR]

We developed a new separation method for isolating placental vascular smooth muscle cells (PVSMCs) from a rat in this study. Our method used the magnetic force between a magnet and ferrous ferric oxide (Fe3O 4) to make the separation and extraction processes easier and more efficient. From the first to sixth generation, the cells isolated using this protocol were identified as smooth muscle cells (SMCs) by their immunoreactivity to the SMC markers and by the "hill and valley" morphology. PVSMCs were exposed to angiotensin II (1 μmol/L) and resulted in sharply increased intracellular Ca 2+ concentration. Furthermore, activation of protein kinase C (PKC) increased concomitantly with a decrease in calponin expression. These results indicate that the isolated cells had biological activity. Our method of isolating PVSMCs from rat leads to isolation of cultured cells with activity and high purity. The approach will be useful in research studies on placental vascular diseases. In this study, we described a simple and efficient method for isolating placental vascular smooth muscle cells (PVSMCs) from rat. The method used the magnetic force between a magnet and ferrous ferric oxide (Fe304) to make the separation and extraction of VSMC. The cells isolated using this protocol were identified as smooth muscle cells (SMCs) by immunoreactivity to the SMC markers and by the "hill and valley" morphology. [ABSTRACT FROM AUTHOR]

Increased vascular resistance in the fetoplacental circulation is a characteristic of preeclampsia. However, the potential molecular mechanisms of this condition remain obscure. The current study aimed to determine the direct effect of the peptide antigen corresponding to the second extracellular loop of the angiotensin II type 1 receptor (AT1R-ECII) activating autoantibody (AT1-AA), a novel risk factor in preeclamptic patients, on fetoplacental villus stem blood vessels. Immunohistochemistry revealed that AT1 receptors were localized in the veins and arteries of human placental villi. Among 58 serum samples from preeclamptic patients, 28 (48.28%) were proved AT1-AA-positive by enzyme-linked immunosorbent assay [ P < 0.01 vs. 2/51 (3.92%) in the normal pregnancy group]. Total IgGs purified from AT1-AA-positive patients' sera (AT1-AA-IgGs) were added to isolated normal human placental blood vessels. The IgG significantly constricted both the villus veins and arteries in a dose-dependent manner in vitro, which could be blocked by the peptide corresponding to the human AT1R-ECII, anti-human IgG or the AT1 receptor antagonist losartan. Additionally, the venous constriction induced by AT1-AA-IgGs remained unchanged even at the end of the experiment (about half an hour), but the vasoconstriction caused by the AT1 receptor agonist angiotensin II underwent desensitization within three minutes. Collectively, our results demonstrated that AT1-AA in preeclamptic sera can directly constrict fetoplacental villus blood vessels without desensitization via the AT1 receptor in vitro, which might contribute to poor fetoplacental perfusion in preeclampsia. J. Cell. Physiol. 228: 142-148, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Cholesteryl ester transfer protein (CETP) plays an important role in reverse cholesterol transport (RCT). To study on the structure and function of CETP in the tree shrew, a kind of animal resistant to atherosclerosis, we completed the cloning of the full-length tree-shrew CETP cDNA sequence based on the reported partial sequence. The full-length cDNA of tree shrew CETP was 1,704 bp and the deduced protein of the cDNA showed a sequence identity of 81, 80 and 74%, respectively, with the human, monkey and rabbit CETP. The level of CETP mRNA in the liver was much more abundant than that in the other tissues. A mutant protein with a substitution of Asn at position 110 by Gln was found to possess an impaired secretion property compared with the wild-type tree shrew CETP. The mutant proteins, respectively, with a substitution of Pro at position 344 by Ser and a substitution of Gln at position 452 by Arg displayed similar secretion ability, but a decreased cholesteryl ester transfer capability compared with the wild type (48 and 26% lower, respectively). These findings demonstrate that liver is the main tissue synthesizing CETP in the tree shrew. Asn at position 110 plays an important role in the secretion of tree shrew CETP. The residues at position 344 and 452 play essential roles in cholesteryl ester transferring process. [ABSTRACT FROM AUTHOR]

Background Agonistic autoantibodies against the angiotensin II type 1 receptor (AT1-AAs) extensively exist in patients with hypertensive diseases and have been demonstrated to play crucial roles in the pathophysiological process of vascular remodeling. However, the treatment options are limited. The large-conductance calcium-activated potassium (BK) channel is a critical regulator and potential therapeutic target of vascular tone and architecture. We have previously observed that AT1-AAs have an inhibitory effect on BK channels. However, whether BK channel dysfunction is involved in AT1-AAs-induced vascular remodeling and the therapeutic effect of BK channel opener is unclear. Methods and Results In our study, mesenteric arteries from AT1-AAs-positive rats exhibited increased wall thickness, narrowing of the arteriolar lumen, and increased collagen accumulation. Patch clamp test results showed that the voltage sensitivity of BK channel declined in mesenteric arteriolar smooth muscle cells from AT1-AAs-positive rats. Experiments with freshly isolated mesenteric arteriolar smooth muscle cells showed that AT1-AAs reduced the opening probability, open levels, open dwell time, and calcium sensitivity of BK channel. Experiments with HEK293T cells transfected with GFP-ZERO-BK α-subunit plasmids suggested a BK channel α-subunit-dependent mechanism. BK channel α-subunit deficient, namely KCNMA1 -/- rats showed a phenotype of mesenteric artery remodeling. The administration of NS1619, a specific BK channel opener targeting the α-subunit, reversed the phenotypic transition and migration induced by AT1-AAs in cultured mesenteric arteriolar smooth muscle cells. Finally, perfusion of NS1619 significantly relieved the pathological effects induced by AT1-AAs in vivo. Conclusions In summary, we provide compelling evidence that BK channel α-subunit dysfunction mediates AT1-AAs-induced mesenteric artery remodeling. Preservation of BK channel activity may serve as a potential strategy for the treatment of AT1-AAs-induced maladaptive resistance artery remodeling.

Adiponectin is an adipocyte-derived hormone, which is closely associated with the development of Alzheimer's disease (AD) and has potential preventive and therapeutic significance. In the present study, we explored the relationship between adiponectin and circadian rhythm disorder in AD, the effect of adiponectin on the abnormal expression of Bmal1 mRNA/protein induced by amyloid-β protein 31-35 (Aβ31-35), and the underlying mechanism of action. We found that adiponectin-knockout mice exhibited amyloid-β deposition, circadian rhythm disorders and abnormal expression of Bmal1. Adiponectin ameliorated the abnormal expression of the Bmal1 mRNA/protein caused by Aβ31-35 by inhibiting the activity of glycogen synthase kinase 3β (GSK3β). These results suggest that adiponectin deficiency could induce circadian rhythm disorders and abnormal expression of the Bmal1 mRNA/protein, whilst exogenous administration of adiponectin may improve Aβ31-35-induced abnormal expression of Bmal1 by inhibiting the activity of GSK3β, thus providing a novel idea for the treatment of AD., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Cardiomyocytes autophagy is essential for maintaining cardiac function. Our previous studies have found that β 1 -adrenergic receptor autoantibody (β 1 -AA) induced the decreased myocardial autophagic flux, which resulted in cardiomyocyte death and cardiac dysfunction. And other studies demonstrated that β 1 -AA induced the decrease of AMPK phosphorylation, the key hub of autophagy pathway, while adiponectin up-regulated autophagic flux mediated by AMPK. However, it is not clear whether adiponectin improves the inhibition of myocardial autophagic flux induced by β 1 -AA by up-regulating the level of AMPK phosphorylation. In this study, it has been confirmed that β 1 -AA induced the decrease of AMPK phosphorylation level in both vivo and vitro. Moreover, pretreatment of cardiomyocytes with AMPK inhibitor Compound C could further reduce the autophagic flux induced by β 1 -AA. Adiponectin deficiency could aggravate the decrease of myocardial AMPK phosphorylation level, autophagic flux and cardiac function induced by β 1 -AA. Further, exogenous adiponectin could reverse the decline of AMPK phosphorylation level and autophagic flux induced by β 1 -AA and even reduce cardiomyocyte death. While pretreated with the Compound C, the adiponectin treatment did not improve the decreased autophagosome formation, but still improved the decreased autophagosome clearance induced by β 1 -AA in cardiomyocytes. This study is the first time to confirm that β 1 -AA could inhibit myocardial autophagic flux by down-regulating AMPK phosphorylation level. Adiponectin could improve the inhibition of myocardial autophagic flux induced by β 1 -AA partly dependent on AMPK, so as to provide an experimental basis for the treatment of patients with β 1 -AA-positive cardiac dysfunction., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Cardiac dysfunction is involved in disorders of energy metabolism. High-titre autoantibodies against the β 1 -adrenoceptor (β 1 -AAs) have been reported to exist in patients with cardiac dysfunction; however, the mechanism by which β 1 -AAs affect cardiac function is unknown. This study aimed to determine whether β 1 -AAs disturb myocardium energy metabolism and cause cardiac dysfunction. β 1 -AA monoclonal antibodies (β 1 -AAmAbs) were successfully pre-synthesized by hybridoma clones and used in all experiments. β 1 -AAmAbs impaired cardiac function and induced a myocardial metabolic disturbance, as evidenced by decreased left ventricular ejection fraction and fractional shortening. In addition, β 1 -AAmAbs decreased the adenosine triphosphate level and increased cardiac energy consumption (rate-pressure product). We further showed that the effects of β 1 -AAmAbs on heart tissue might involve the mitochondria and metabolic pathways via the β 1 -adrenoceptor based on an immunoprecipitation and mass spectrometry. Additionally, we found that β 1 -AAmAbs impaired myocardial mitochondrial structure, decreased the membrane potential, and induced insufficient mitophagy. In conclusion, β 1 -AAmAb-induced cardiac dysfunction is partly due to a disturbance in myocardial energy metabolism., (© 2021 John Wiley & Sons Australia, Ltd.)

Background Autoantibodies against the second extracellular loop of the β 1 -adrenoceptor (β 1 - AA ) act similarly to agonist of β 1 -adrenergic receptor, which plays an important role in the pathophysiological characteristics of ventricular remodeling. Recently, considerable lines of evidence have suggested that CTRP9 (C1q tumor necrosis factor-related protein 9) is a potent cardioprotective cardiokine and protects the heart from ventricular remodeling. The aim of this study was to determine the role of CTRP 9 in ventricular remodeling induced by β 1 - AA . Methods and Results Blood samples were collected from 131 patients with coronary heart disease and 131 healthy subjects. The serum levels of β 1 - AA and CTRP 9 were detected using ELISA . The results revealed that CTRP 9 levels in β 1 - AA -positive patients were lower than those in β 1 - AA -negative patients, and serum CTRP 9 concentrations were inversely correlated with β 1 - AA . β 1 - AA monoclonal antibodies (β 1 - AA mAbs) were administered in mice with and without rAAV 9- cTnT -Full Ctrp9- FLAG virus for 8 weeks. Reverse transcription-polymerase chain reaction/Western analysis showed that cardiomyocyte CTRP 9 expression was significantly reduced in β 1 - AA mAb-treated mice. Moreover, compared with the β 1 - AA mAb alone group, cardiac-specific CTRP 9 overexpression improved cardiac function, attenuated adverse remodeling, and ameliorated cardiomyocyte apoptosis and fibrosis. Mechanistic studies demonstrated that CTRP 9 overexpression decreased the levels of G-protein-coupled receptor kinase 2 and promoted the activation of AMP-dependent kinase pathway. However, cardiac-specific overexpression of CTRP 9 had no effect on the levels of  cAMP and protein kinase A activity elevated by β 1 -AAmAb. Conclusions This study provides the first evidence that the long-term existence of β 1 - AA mAb suppresses cardiac CTRP 9 expression and exaggerates cardiac remodeling, suggesting that CTRP 9 may be a novel therapeutic target against pathologic remodeling in β 1 - AA -positive patients with coronary heart disease.