Casting Light on the Janus-Faced HMG-CoA Reductase Degradation Protein 1: A Comprehensive Review of Its Dualistic Impact on Apoptosis in Various Diseases.

Nowadays, it is well recognized that apoptosis, as a highly regulated cellular process, plays a crucial role in various biological processes, such as cell differentiation. Dysregulation of apoptosis is strongly implicated in the pathophysiology of numerous disorders, making it essential to comprehend its underlying mechanisms. One key factor that has garnered significant attention in the regulation of apoptotic pathways is HMG-CoA reductase degradation protein 1, also known as HRD1. HRD1 is an E3 ubiquitin ligase located in the endoplasmic reticulum (ER) membrane. Its primary role involves maintaining the quality control of ER proteins by facilitating the ER-associated degradation (ERAD) pathway. During ER stress, HRD1 aids in the elimination of misfolded proteins that accumulate within the ER. Therefore, HRD1 plays a pivotal role in the regulation of apoptotic pathways and maintenance of ER protein quality control. By targeting specific protein substrates and affecting apoptosis-related pathways, HRD1 could be an exclusive therapeutic target in different disorders. Dysregulation of HRD1-mediated processes contributes significantly to the pathophysiology of various diseases. The purpose of this review is to assess the effect of HRD1 on the pathways related to apoptosis in various diseases from a therapeutic perspective.

Pragmatic features in patients with schizophrenia.

Schizophrenia is a heterogeneous disorder. Despite the fact that communication and language skills may be impaired in schizophrenia, only a few studies have examined specific aspects of pragmatic competence in these patients. Therefore, this study aimed to compare the pragmatic skills of schizophrenic patients and a control group. Forty-three schizophrenic patients with a Mean ± SD age of 40 ± 1.21 years old and a control group were assessed using the Adult Pragmatics Profile (APP), which is a validated tool consisting of three scales: verbal, nonverbal and paralinguistic. The participants in the schizophrenia group demonstrated significant impairments in pragmatic abilities compared to the participants in those the control group. The most remarkable difference was in the nonverbal scale (5.00 ± 1.09), while the lowest difference was seen in the verbal scale (18.30 ± 3.91). Within the nonverbal subscales, eye contact was the most impaired. Schizophrenic patients presented with impairments in their pragmatic skills (verbal, nonverbal and paralinguistic). As pragmatic skills play a paramount role in social communication, it is of great significance to address these impairments to enhance patients' quality of life.

Pragmatic deficits are a core feature in schizophrenic patients.Schizophrenic patients had the lowest scores on the nonverbal scale, and they showed the lowest impairment on the verbal scale.Schizophrenic patients scored the lowest on the turn-taking subscale of the verbal scale, the eye contact of the non-verbal scale and the vocal intensity subscale of the paralinguistic scale of the APP.

HRD1 in human malignant neoplasms: Molecular mechanisms and novel therapeutic strategy for cancer.

In tumor cells, the endoplasmic reticulum (ER) plays an essential role in maintaining cellular proteostasis by stimulating unfolded protein response (UPR) underlying stress conditions. ER-associated degradation (ERAD) is a critical pathway of the UPR to protect cells from ER stress-induced apoptosis and the elimination of unfolded or misfolded proteins by the ubiquitin-proteasome system (UPS). 3-Hydroxy-3-methylglutaryl reductase degradation (HRD1) as an E3 ubiquitin ligase plays an essential role in the ubiquitination and dislocation of misfolded protein in ERAD. In addition, HRD1 can target other normal folded proteins. In various types of cancer, the expression of HRD1 is dysregulated, and it targets different molecules to develop cancer hallmarks or suppress the progression of the disease. Recent investigations have defined the role of HRD1 in drug resistance in types of cancer. This review focuses on the molecular mechanisms of HRD1 and its roles in cancer pathogenesis and discusses the worthiness of targeting HRD1 as a novel therapeutic strategy in cancer.

Cardiac amyloidosis: diagnostic challenges and recent advancement in the treatment of transthyretin amyloidosis (ATTR).

ATTR-CA is an under-reported cause of congestive heart failure (CHF) and cardiac arrhythmias. Heightened clinical suspicion along with a multimodal investigative approach is often required in diagnosing this potentially fatal condition. Tafamidis and inotersen have shown promising results in terms of progression-free survival by ameliorating CHF symptoms and peripheral neuropathies in clinical trials. In this case series of five patients, we present three wild-type cardiac amyloidosis (ATTRwt-CA), one familial cardiac amyloidosis (ATTRm-CA) and one primary cardiac (AL-CA). The diagnostic modality was different for each patient. ATTRwt-CA, ATTRm-CA and AL-CA patients received tafamidis, inotersen and chemotherapy with bone marrow stem-cell transplantation, respectively.

Complicated Spontaneous Coronary Artery Dissection (SCAD) Culminating in Aneurysm Formation: Coronary Artery Bypass Graft Surgery Is Preferable Over Percutaneous Coronary Intervention in Peripartum SCAD.

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome (ACS), most frequently occurring in young females of reproductive age, and has a high mortality rate. Currently, no guidelines are available to direct treatment. We report a case of a 29-year-old female with complications of SCAD treated with coronary artery bypass graft (CABG), resulting in a better outcome as compared to that of percutaneous coronary intervention (PCI). Our patient presented with class IV angina one-year post-PCI following postpartum SCAD. Left heart catheterization (LHC) reported SCAD involving the ostium of the left circumflex (LCX) and then cutting off the left marginal artery, which was followed by a 2.5 x 28 mm Synergy drug-eluting stent (Boston Scientific, Marlborough, MA) x1 in the lateral branch of the bifurcating marginal system with good coronary stent results. Repeat LHC one-year after the SCAD was significant for a large aneurysm in the distal left main coronary artery (LCA) extending into the LCX with evidence of a residual large false lumen (0.41 sq cm), as compared to the narrow segment of the true lumen (0.15 sq cm). Compared to the distal LCA area (0.49 sq cm), the true lumen of the LCA had severe stenosis. The patient underwent three-vessel CABG (left internal mammary artery (LIMA)-> left anterior descending artery (LAD), right internal mammary artery (RIMA)->first obtuse marginal (OM1), saphenous vein graft (SVG)->second obtuse marginal (OM2)) with sternal plating. The patient was doing well three months post-CABG with complete resolution of the pain, which was unattainable by PCI. Our report suggests that CABG may be preferable over PCI in the peripartum SCAD to avoid complications or sudden cardiac death from the extension of the dissection and aneurysm formation.

Pill to Pain: First Case of Topiramate-Induced Chronic Spontaneous Coronary Artery Dissection (SCAD).

Spontaneous coronary artery dissection (SCAD) is a non-traumatic, non-iatrogenic, and non-atherosclerotic coronary artery disorder that manifests clinically as acute coronary syndrome (ACS), arrhythmia, or sudden cardiac death (SCD). It is a rare cause of ACS (1.7%-4%) and SCD (0.5%), more common in women than men. It was first reported in 1931 in a 42-year-old female at autopsy, who had SCAD after violent retching and vomiting. We report a case of a 51-year-old female who developed sudden-onset chest pain after taking topiramate (TPM). Her chest pain persisted for 1.5 months prior to her outpatient evaluation, which led to further cardiac workup. An urgent left heart catheterization (LHC) revealed a SCAD. Her symptoms improved with percutaneous coronary intervention (PCI), and she was discharged home on aspirin, statins, and beta-blockers.

STEMI associated with SARS-CoV-2 infection and the use of ECMO as a potential therapeutic approach in addition to the PCI.

A 55-year-old male presented to the emergency department with the complaints of chest pain that started 4 h before presentation. Pain was located over the anterior chest, 5 out of 10 intensity, with radiation to the left arm. Chest x-ray on admission showed severe diffuse bilateral pulmonary infiltrates concerning for COVID-19 pneumonia. Electrocardiogram showed inferior and lateral ST-segment elevation compatible with acute inferolateral myocardial infarction. Successful percutaneous coronary intervention (PCI) of the proximal and mid-right coronary artery using the balloon angioplasty and drug-eluting stent was performed. Post-PCI stenosis was 0% with a thrombolysis in myocardial infarction (TIMI) flow of 3. Five-day course of azithromycin and hydroxychloroquine was completed with no improvement overall. Patient received two doses of 400 mg of tocilizumab intravenously on hospital days 5 (HD#5) and #6. The patient was proned, on FiO2 100%, PEEP 15 cm H2O, on epoprostenol sodium and paralytics and eventually received venovenous ECMO, which improved outcome.

Spontaneous Coronary Artery Dissection: An Unusual Cause of ST-Elevation Myocardial Infarction in Young Males.

Spontaneous coronary artery dissection (SCAD) is a non-traumatic, non-iatrogenic, and non-atherosclerotic coronary artery disorder that manifests clinically as an acute coronary syndrome (ACS), arrhythmia, or sudden cardiac death (SCD). It is a rare cause of ACS (1.7-4%) and SCD (0.5%), more commonly in women than men. It is rarely reported in males. We report a case of acute ST-elevation myocardial infarction (STEMI) due to SCAD in a 44-year-old healthy male.

The inability of an early post-transplantation intrarenal resistive index to predict renal allograft function at 12 weeks after engraftment in young adults.

Background The intrarenal resistive index (RI) is a promising tool for predicting renal graft outcomes. Due to the complexity of graft function and the presence of diverse contributing factors, however, the available data are inconclusive. Purpose To examine the performance of the RI 1 week after transplant in predicting allograft function at week 12, with an emphasis on the type of intrarenal artery used in the examination. Material and Methods A total of 58 first-time living-donor kidney-allograft-transplantation patients aged less than 50 years underwent Doppler ultrasonography (US) of the intrarenal arteries 1 week after engraftment. The RI was calculated for both the segmental (RI-C) and interlobar-arcuate (RI-P) arteries. Serum creatinine level and the creatinine reduction ratio (CRR) were determined at weeks 1 and 12 post transplantation. Results While the RI did not correlate with serum creatinine level and CRR at week 1, significant correlations were present between the RI and serum creatinine level (r = 0.28, P = 0.03 for both RI-C and RI-P) and CRR (r = -0.25, P = 0.05 for both RI-C and RI-P) at week 12. The sensitivity, specificity, positive predictive value, and negative predictive value of using RI-C in predicting abnormal 12-week serum creatinine level were 51.2%, 52.9%, 72.4%, and 31.3%, respectively; and 53.7%, 47.1%, 70.9%, and 29.6% for RI-P, respectively ( P > 0.99 for all comparisons). Conclusion Early post-transplantation RI correlates significantly with both serum creatinine level and creatinine reduction ratio 12 weeks after engraftment with intermediate predictive accuracy.