Cardiac-derived CTRP9 protects against myocardial ischemia/reperfusion injury via calreticulin-dependent inhibition of apoptosis.

Cardiokines play an essential role in maintaining normal cardiac functions and responding to acute myocardial injury. Studies have demonstrated the heart itself is a significant source of C1q/TNF-related protein 9 (CTRP9). However, the biological role of cardiac-derived CTRP9 remains unclear. We hypothesize cardiac-derived CTRP9 responds to acute myocardial ischemia/reperfusion (MI/R) injury as a cardiokine. We explored the role of cardiac-derived CTRP9 in MI/R injury via genetic manipulation and a CTRP9-knockout (CTRP9-KO) animal model. Inhibition of cardiac CTRP9 exacerbated, whereas its overexpression ameliorated, left ventricular dysfunction and myocardial apoptosis. Endothelial CTRP9 expression was unchanged while cardiomyocyte CTRP9 levels decreased after simulated ischemia/`reperfusion (SI/R) in vitro. Cardiomyocyte CTRP9 overexpression inhibited SI/R-induced apoptosis, an effect abrogated by CTRP9 antibody. Mechanistically, cardiac-derived CTRP9 activated anti-apoptotic signaling pathways and inhibited endoplasmic reticulum (ER) stress-related apoptosis in MI/R injury. Notably, CTRP9 interacted with the ER molecular chaperone calreticulin (CRT) located on the cell surface and in the cytoplasm of cardiomyocytes. The CTRP9-CRT interaction activated the protein kinase A-cAMP response element binding protein (PKA-CREB) signaling pathway, blocked by functional neutralization of the autocrine CTRP9. Inhibition of either CRT or PKA blunted cardiac-derived CTRP9\u27s anti-apoptotic actions against MI/R injury. We further confirmed these findings in CTRP9-KO rats. Together, these results demonstrate that autocrine CTRP9 of cardiomyocyte origin protects against MI/R injury via CRT association, activation of the PKA-CREB pathway, ultimately inhibiting cardiomyocyte apoptosis

Table_1_Parkinson's disease and comorbid myasthenia gravis: a case report and literature review.docx

BackgroundParkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Myasthenia gravis (MG) is a rare autoimmune disease caused by antibodies against the neuromuscular junction. PD and comorbid MG are rarely seen.Case presentationHere we report on a patient who was diagnosed with PD and MG. A 74-year-old man had a 4-year history of bradykinesia and was diagnosed with PD. He subsequently developed incomplete palpebral ptosis, apparent dropped head, and shuffling of gait. The results of neostigmine tests were positive. Repetitive nerve stimulation (RNS) showed significant decremental responses at 3 and 5 Hz in the orbicularis oculi. The patient's anti-acetylcholine receptor (anti-AchR) antibody serum level was also elevated. Meanwhile, 9-[18F]fluoropropyl-(+)-dihydrotetrabenazine positron emission tomography–computed tomography (18F-AV133 PET-CT) scan revealed a significant decrease in uptake in the bilateral putamen. After addition of cholinesterase inhibitors, his symptoms of palpebral ptosis and head drop improved greatly and he showed a good response to levodopa.ConclusionAlthough PD with MG is rare, we still need to notice the possibility that a PD patient may have comorbid MG. The underlying mechanism of PD and comorbid MG remains unknown, but an imbalance between the neurotransmitters dopamine and acetylcholine and the immune system are likely to play significant roles in the pathogenesis. In this article, we present our case and a literature review on the co-occurrence of PD and MG, reviewing their clinical features, and discuss the underlying pathogenic mechanism of this comorbidity.</p

Video_1_Parkinson's disease and comorbid myasthenia gravis: a case report and literature review.MP4

BackgroundParkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Myasthenia gravis (MG) is a rare autoimmune disease caused by antibodies against the neuromuscular junction. PD and comorbid MG are rarely seen.Case presentationHere we report on a patient who was diagnosed with PD and MG. A 74-year-old man had a 4-year history of bradykinesia and was diagnosed with PD. He subsequently developed incomplete palpebral ptosis, apparent dropped head, and shuffling of gait. The results of neostigmine tests were positive. Repetitive nerve stimulation (RNS) showed significant decremental responses at 3 and 5 Hz in the orbicularis oculi. The patient's anti-acetylcholine receptor (anti-AchR) antibody serum level was also elevated. Meanwhile, 9-[18F]fluoropropyl-(+)-dihydrotetrabenazine positron emission tomography–computed tomography (18F-AV133 PET-CT) scan revealed a significant decrease in uptake in the bilateral putamen. After addition of cholinesterase inhibitors, his symptoms of palpebral ptosis and head drop improved greatly and he showed a good response to levodopa.ConclusionAlthough PD with MG is rare, we still need to notice the possibility that a PD patient may have comorbid MG. The underlying mechanism of PD and comorbid MG remains unknown, but an imbalance between the neurotransmitters dopamine and acetylcholine and the immune system are likely to play significant roles in the pathogenesis. In this article, we present our case and a literature review on the co-occurrence of PD and MG, reviewing their clinical features, and discuss the underlying pathogenic mechanism of this comorbidity.</p

Elderly-Onset Paroxysmal Kinesigenic Dyskinesia: A Case Report

Article full text The article associated with this page has been accepted for online publication and is in the final stages of production. The link to the full text will be made available on this page in the next few days. The above patient video represents the opinions of the authors. For a full list of declarations, including funding and author disclosure statements, please see the full text online (see “read the peer-reviewed publication” opposite).  © The authors, CC-BY-NC 2022.  </p

Intraocular pressure <it>vs</it> intracranial pressure in disease conditions: A prospective cohort study (Beijing iCOP study)

Abstract Background The correlation between intracranial pressure (ICP) and intraocular pressure (IOP) is still controversial in literature and hence whether IOP can be used as a non-invasive surrogate of ICP remains unknown. The aim of the current study was to further clarify the potential correlation between ICP and IOP. Methods The IOP measured with Goldmann applanation tonometer was carried out on 130 patients whose ICP was determined via lumber puncture. The Pearson correlation coefficient between ICP and IOP was calculated, the fisher line discriminated analysis to evaluate the effectivity of using IOP to predict the ICP level. Results A significant correlation between ICP and IOP was found. ICP was correlated significantly with IOP of the right eyes (p  Conclusion Our data suggested that although a significant correlation exists between ICP and IOP, caution needs to be taken when using IOP readings by Goldmann applanation tonometer as a surrogate for direct cerebrospinal fluid pressure measurement of ICP.</p

The alternative crosstalk between RAGE and nitrative thioredoxin inactivation during diabetic myocardial ischemia-reperfusion injury.

The receptor for advanced glycation end products (RAGE) and thioredoxin (Trx) play opposing roles in diabetic myocardial ischemia-reperfusion (MI/R) injury. We recently demonstrated nitrative modification of Trx leads to its inactivation and loss of cardioprotection. The present study is to determine the relationship between augmented RAGE expression and diminished Trx activity pertaining to exacerbated MI/R injury in the diabetic heart. The diabetic state was induced in mice by multiple intraperitoneal low-dose streptozotocin injections. RAGE small-interfering RNA (siRNA) or soluble RAGE (sRAGE, a RAGE decoy) was via intramyocardial and intraperitoneal injection before MI/R, respectively. Mice were subjected to 30 min of myocardial infarction followed by 3 or 24 h of reperfusion. At 10 min before reperfusion, diabetic mice were randomized to receive EUK134 (peroxynitrite scavenger), recombinant hTrx-1, nitrated Trx-1, apocynin (a NADPH oxidase inhibitor), or 1400W [an inducible nitric oxide synthase (iNOS) inhibitor] administration. The diabetic heart manifested increased RAGE expression and N(ε)-(carboxymethyl)lysine (CML, major advanced glycation end product subtype) content, reduced Trx-1 activity, and increased Trx nitration after MI/R. RAGE siRNA or administration of sRAGE in diabetic mice decreased MI/R-induced iNOS and gp91(phox) expression, reduced Trx nitration, preserved Trx activity, and decreased infarct size. Apocynin or 1400W significantly decreased nitrotyrosine production and restored Trx activity. Conversely, administration of either EUK134 or reduced hTrx, but not nitrated hTrx, attenuated MI/R-induced superoxide production, RAGE expression, and CML content and decreased cardiomyocyte apoptosis in diabetic mice. Collectively, we demonstrate that RAGE modulates the MI/R injury in a Trx nitrative inactivation fashion. Conversely, nitrative modification of Trx blocked its inhibitory effect upon RAGE expression in the diabetic heart. This is the first direct evidence demonstrating the alternative cross talk between RAGE overexpression and nitrative Trx inactivation, suggesting that interventions interfering with their interaction may be novel means of mitigating diabetic MI/R injury