Advances in stem cell-based therapeutics for acute high-altitude illness: research progress and prospects.

Acute high-altitude illness (AHAI), triggered by hypobaric hypoxia following rapid ascent to high elevations, induces complex pathophysiological responses that may be life-threatening. Recent advances in regenerative medicine have highlighted the therapeutic potential of stem cells in mitigating hypoxia-induced damage. Among them, Mesenchymal stem cells (MSCs), the most extensively investigated, exert therapeutic efficacy through immunomodulation, attenuation of oxidative stress, and enhancement of tissue repair mechanisms.

Synthesis and evaluation of a novel class of spiro[chromene-2,2'-indoline] derivatives as potent inhibitors of peptidylarginine deiminase IV to treat rheumatoid arthritis.

Peptidylarginine deiminase isoform 4 (PADI4) is a potential therapeutic target for treatment of rheumatoid arthritis. Auto-antibodies induced by the dysregulated catalysis of peptidylarginine into peptidylcitrulline by PADI4 can cause the onset and progression of rheumatoid arthritis. Herein, we report a novel class of spiro[chromene-2,2'-indoline] derivatives which were synthesized and optimized from a hit discovered by screening two libraries with 3760-members of natural products and derivatives for PADI4 inhibitors.

Midterm Outcomes of Transcatheter Closure of Anastomotic Leak after Ascending Aortic Surgery.

This study aimed to evaluate the safety and durability of transcatheter closure of anastomotic leak (AL) after ascending aortic (AAo) surgery.From 2016 to 2021, we performed transcatheter closure for 22 patients aged 56.9 ± 12 years (19 male, 86.

In-vivo biomechanical characteristics analysis of ascending aortic aneurysm using multidimensional dynamic CTA.

This study utilized multidimensional dynamic computed tomography angiography (MD-CTA) to analyze the biomechanical characteristics of ascending thoracic aortic aneurysms (ATAA) in 30 subjects: 20 ATAA patients (12 with Marfan syndrome and 8 without) and 10 healthy individuals without ascending aortic disease. Aortic models were reconstructed from CTA images, and multi-phase displacement data were obtained via image registration. The inverse finite element method (iFEM) was applied to calculate wall tension, and displacement data was used to calculate wall strain, from which strain-tension curves were fitted.

Novel susceptibility gene SLC23A2 functions via PI3K-AKT-mTOR pathway in etiology of non-syndromic cleft palate.

The biological interactions between genetic and environmental modifiers play critical roles in the etiology of non-syndromic orofacial cleft (NSOC), but it is rarely studied. This study selected 47 environmental related genes from the metabolic pathways of smoking, drinking, hypoxia, and vitamins (including vitamin A, vitamin B9 (folic acid), vitamin C (ascorbic acid), vitamin D, and vitamin E), and test their associations with NSOC and its subtypes. We found that a novel gene SLC23A2, the vitamin C transporter gene is significantly associated with non-syndromic cleft palate only (NSCPO) (p = 3.

Carnosic acid, a novel food-source AT1R antagonist and its anti-hypertension mechanism.

Hypertension is the most prevalent non-communicable disease, affecting billions of people worldwide. Discovery and development of natural antihypertensive lead compounds or drugs are important to resolve the limitations of existing antihypertensive drug safety and resistance. This investigation verified that carnosic acid (CA), an important active ingredient of rosemary, an edible spice plant, indicates a significant anti-hypertensive activity in spontaneous hypertension rats by targeting AT1R.

Early and mid-term outcomes of open thoracoabdominal aortic aneurysm repair after thoracic endovascular aortic repair.

Objective: To evaluate the early and mid-term outcomes of open repair in patients with thoracoabdominal aortic aneurysm (TAAA) after thoracic endovascular aortic repair (TEVAR).

Methods: This was a retrospective single center study. Data were retrospectively collected and analyzed for consecutive patients undergoing open TAAA repair (TAAAR) after TEVAR from November 2016 to June 2021.

Vitamin B12 inhibits peptidylarginine deiminases and ameliorates rheumatoid arthritis in CAIA mice.

Rheumatoid arthritis is an autoimmune disease whose early onset correlates with dysregulated citrullination, a process catalyzed by peptidylarginine deiminase isoform 4 (PADI-4). Here, we report that PADI-4 is a novel target of vitamin B12, a water-soluble vitamin that serves as a cofactor in DNA synthesis and the metabolism of fatty and amino acids. Vitamin B12 preferentially inhibited PADI-4 over PADI-2 with comparable inhibitory activity to the reference compound Cl-amidine in enzymatic inhibition assays, and reduced total cellular citrullination levels including that of histone H3 citrullination mediated by PADI-4.

Nerve Growth Factor/Tyrosine Kinase A Receptor Pathway Enhances Analgesia in an Experimental Mouse Model of Bone Cancer Pain by Increasing Membrane Levels of δ-Opioid Receptors.

Background: The role of nerve growth factor (NGF)/tyrosine kinase A receptor (TrKA) signaling, which is activated in a variety of pain states, in regulating membrane-associated δ-opioid receptor (mDOR) expression is poorly understood. The hypothesis was that elevated NGF in bone cancer tumors could upregulate mDOR expression in spinal cord neurons and that mDOR agonism might alleviate bone cancer pain.

Methods: Bone cancer pain (BCP) was induced by inoculating Lewis lung carcinoma cells into the femoral marrow cavity of adult C57BL/6J mice of both sexes.

Larger deep white matter hyperintensity volume correlates with more severe social behavioral changes in patients with subacute ischemic stroke.

Background: Changes in social behavior can occur after ischemic stroke. We aimed to investigate the potential correlations between neuroimaging variables and changes in social behavior in patients who experienced subacute ischemic stroke.

Methods: We prospectively screened patients with first-ever ischemic stroke.

Integrated Analysis of the Association Between Variants at and NSCL/P in the Han Population.

Objective: Paired box 7 () has been considered as a candidate gene for non-syndromic cleft lip with or without palate (NSCL/P). However, there is no research for the XXX, and previous studies concentrated on limited variants. This study aimed to conduct sufficiently dense and powerful scans of variants at and explored the roles of variants at in NSCL/P among the XXX.

Causal Variations at Gene Identified in Van der Woude Syndrome Pedigrees.

The purpose of this study is to analyze the clinical characteristics of patients with Van der Woude syndrome (VWS) and to detect variations in each patient. Finally, the combination of genotype and phenotype can make a clear diagnosis of VWS patients with different phenotype penetrance. Five Chinese VWS pedigree were enrolled.

Right Cortical Infarction and a Reduction in Putamen Volume May Be Correlated with Empathy in Patients after Subacute Ischemic Stroke-A Multimodal Magnetic Resonance Imaging Study.

Empathy has not been well studied in patients following ischemic stroke. We aimed to evaluate the relationships of multimodal neuroimaging parameters with the impairment of empathy in patients who had experienced subacute ischemic stroke. Patients who had experienced a first-event acute ischemic stroke were recruited, and we assessed their empathy using the Chinese version of the Empathy Quotient (EQ) 3 months after the index stroke.

Lumbar disc sequestration mimicking a tumor: Report of four cases and a literature review.

Background: Disc herniation refers to the displacement of disc material beyond its anatomical space. Disc sequestration is defined as migration of the herniated disc fragment into the epidural space, completely separating it from the parent disc. The fragment can move in upward, inferior, and lateral directions, which often causes low back pain and discomfort, abnormal sensation, and movement of lower limbs.

Tyrphostin AG1024 Suppresses Coronaviral Replication by Downregulating JAK1 via an IR/IGF-1R Independent Proteolysis Mediated by Ndfip1/2_NEDD4-like E3 Ligase Itch.

JAK1 depletion or downregulation was previously reported to account for coronavirus inhibition. Here, we found that AG1024, an IR (insulin receptor) and IGF-1R (insulin-like growth factor 1 receptor) inhibitor, diminishes JAK1 protein levels and exerts anti-coronaviral activities with EC values of 5.2 ± 0.

Remdesivir and Cyclosporine Synergistically Inhibit the Human Coronaviruses OC43 and SARS-CoV-2.

Remdesivir, a prodrug targeting RNA-dependent-RNA-polymerase, and cyclosporine, a calcineurin inhibitor, individually exerted inhibitory activity against human coronavirus OC43 (HCoV-OC43) in HCT-8 and MRC-5 cells at EC values of 96 ± 34 ∼ 85 ± 23 nM and 2,920 ± 364 ∼ 4,419 ± 490 nM, respectively. When combined, these two drugs synergistically inhibited HCoV-OC43 in both HCT-8 and MRC-5 cells assayed by immunofluorescence assay (IFA). Remdesivir and cyclosporine also separately reduced IL-6 production induced by HCoV-OC43 in human lung fibroblasts MRC-5 cells with EC values of 224 ± 53 nM and 1,292 ± 352 nM, respectively; and synergistically reduced it when combined.

Spinal epidural hematoma after spinal manipulation therapy: Report of three cases and a literature review.

Background: Spinal manipulation therapy (SMT) has been widely used worldwide to treat musculoskeletal diseases, but it can cause serious adverse events. Spinal epidural hematoma (SEH) caused by SMT is a rare emergency that can cause neurological dysfunction. We herein report three cases of SEH after SMT.

Inhibition of SARS-CoV-2 by Highly Potent Broad-Spectrum Anti-Coronaviral Tylophorine-Based Derivatives.

Tylophorine-based compounds and natural cardiotonic steroids (cardenolides and bufadienolides) are two classes of transmissible gastroenteritis coronavirus inhibitors, targeting viral RNA and host cell factors, respectively. We tested both types of compounds against two types of coronaviruses, to compare and contrast their antiviral properties, and with view to their further therapeutic development. Examples of both types of compounds potently inhibited the replication of both feline infectious peritonitis virus and human coronavirus OC43 with EC values of up to 8 and 16 nM, respectively.