MCM8-mediated mitophagy protects vascular health in response to nitric oxide signaling in a mouse model of Kawasaki disease.

Mitophagy is a major quality control pathway that removes unwanted or dysfunctional mitochondria and plays an essential role in vascular health. Here we show that MCM8 expression is significantly decreased in children with Kawasaki disease (KD) who developed coronary artery aneurysms. Mechanistically, we discovered that nitric oxide signaling promotes TRIM21-mediated MCM8 ubiquitination, which disrupts its interaction with MCM9 and promotes its cytosolic export.

Heterozygous de novo dominant negative mutation of REXO2 results in interferonopathy.

Mitochondrial RNA (mtRNA) in the cytosol can trigger the innate immune sensor MDA5, and autoinflammatory disease due to type I IFN. Here, we show that a dominant negative mutation in the gene encoding the mitochondrial exonuclease REXO2 may cause interferonopathy by triggering the MDA5 pathway. A patient characterized by this heterozygous de novo mutation (p.

Interleukin-34 and immune checkpoint inhibitors: Unified weapons against cancer.

Interleukin-34 (IL-34) is a cytokine that is involved in the regulation of immune cells, including macrophages, in the tumor microenvironment (TME). Macrophages are a type of immune cell that can be found in large numbers within the TME and have been shown to have a role in the suppression of immune responses in cancer. This mmune suppression can contribute to cancer development and tumors' ability to evade the immune system.

Aging of mesenchymal stem cell: machinery, markers, and strategies of fighting.

Human mesenchymal stem cells (MSCs) are primary multipotent cells capable of differentiating into osteocytes, chondrocytes, and adipocytes when stimulated under appropriate conditions. The role of MSCs in tissue homeostasis, aging-related diseases, and cellular therapy is clinically suggested. As aging is a universal problem that has large socioeconomic effects, an improved understanding of the concepts of aging can direct public policies that reduce its adverse impacts on the healthcare system and humanity.

Organellar homeostasis and innate immune sensing.

A cell is delimited by numerous borders that define specific organelles. The walls of some organelles are particularly robust, such as in mitochondria or endoplasmic reticulum, but some are more fluid such as in phase-separated stress granules. Either way, all organelles can be damaged at times, leading their contents to leak out into the surrounding environment.

Heterozygous loss of Dip2B enhances tumor growth and metastasis by altering immune microenvironment.

Cancer is caused by abnormal cell growth and metastasis to other tissues. Development of cancers is complex and underlining mechanisms are mostly unknown. Disco-interacting protein 2 homolog B (DIP2B) is a member of Dip2.

Age-Based Disparities in Metastatic Melanoma Patients Treated in the Immune Checkpoint Inhibitors (ICI) Non-ICI Era: A Population-Based Study.

Immune checkpoint inhibitors (ICIs) have revolutionized metastatic melanoma treatment, but our knowledge of ICI activity across age groups is insufficient. Patients in different age groups with advanced melanoma were selected based on the ICI approval time in this study. Patients with melanoma were identified in the Surveillance, Epidemiology, and End Result (SEER) database program 2004-2016.

Differential effects of Huaier aqueous extract on human CD4T lymphocytes from patients with primary immune thrombocytopenia.

Huaier, a traditional Chinese medicine, is currently used to treat certain types of cancer in the clinic and is also regarded as an immune-modulating and immune-enhancing agent that regulates immune cells. Emerging evidence indicates that an imbalance of immune cells, such as CD4 T helper (Th) lymphocytes, contributes to the progression of immune thrombocytopenia (ITP), but the effects of Huaier on the regulation of CD4 T cells are not yet fully elucidated. In the present study, Jurkat cells and peripheral blood mononuclear cells (PBMCs) from patients with ITP and healthy volunteers were treated with Huaier aqueous extract (HR).

Brain and heart-specific death in cancer patients: Population-based study.

Background: The occurrence of cardiovascular events is a major cause of death in patients with cancer. Small studies have documented a connection between specific brain alterations and autonomic cardiac dysfunctions, possibly resulting in a worse prognosis. We aimed to refine the knowledge of fatal cardiac events in patients with brain metastasis (BM).

Can bipolar transurethral enucleation of the prostate be a better alternative to the bipolar transurethral resection of the prostate?: A prospective comparative study.

To analyze the efficacy and safety between bipolar transurethral enucleation of the prostate (BipoLEP) and bipolar transurethral resection of the prostate (B-TURP).One hundred twenty eight patients with benign prostatic hyperplasia were recruited and divided into group 1 (BipoLEP group, n = 72) and group 2 (B-TURP group, n = 56). The study period was from October 2016 to February 2019.

Surgery Treatment Improved the Overall Survival Rate in Locoregional Myxoid Leiomyosarcoma than Other Myxosarcomas in the United States.

Myxosarcomas are rare malignant tumors of soft connective tissues, classified into various subtypes, including myxoid liposarcoma, myxoid chondrosarcoma, and myxoid leiomyosarcoma. In this study, we proposed to study the demographic, tumor characteristics, and overall survival rate and compared the treatment modalities between these cancers. Patient data collected based on locoregional metastasis presentation of the abovementioned tumors with a cutoff study of survival duration up to 10 years were obtained from the SEER database during 1975-2016.

PD-1/PDL-1 Inhibitors and Cardiotoxicity; Molecular, Etiological and Management Outlines.

Background: The US Food and Drug Administration (FDA) has approved several immunotherapeutic drugs for cancer since 2010, and many more are still being evaluated in other clinical studies. These inhibitors significantly increase response rates and result in the treatment of patients with advanced cancer. However, cancer immunotherapy leads to essential cardiac toxicity properties that have become distinct from other cancer patients' care and are mostly related to their etiology.

Protective Effects of Cinnamaldehyde against Mesenteric Ischemia-Reperfusion-Induced Lung and Liver Injuries in Rats.

The aim of this study was to characterize and reveal the protective effects of cinnamaldehyde (CA) against mesenteric ischemia-reperfusion- (I/R-) induced lung and liver injuries and the related mechanisms. Sprague-Dawley (SPD) rats were pretreated for three days with 10 or 40 mg/kg/d, ig of CA, and then induced with mesenteric ischemia for 1 h and reperfusion for 2 h. The results indicated that pretreatment with 10 or 40 mg/kg of CA attenuated morphological damage in both lung and liver tissues of mesenteric I/R-injured rats.

EnDuo, a novel derivative of Endostar, inhibits the migration of colon cancer cells, suppresses matrix metalloproteinase-2/9 expression and impedes AKT/ERK activation.

Background/aims: Colon cancer remains a life-threating disease with increasing morbidity and mortality worldwide despite the advancement in modern medical treatment. Therefore, novel and effective anti-colon cancers drugs are urgently needed. In this study, we investigated the anti-metastatic property EnDuo, a modified version of Endostar, and the underlying mechanisms.

TL1A/TNFR2 Axis Enhances Immunoregulatory Effects of Bone Marrow Derived Mesenchymal Stem Cell by Indian Hedgehog Signaling Pathway.

Background And Objectives: The immunomodulatory potential of mesenchymal stem cells (MSCs) can be regulated by a variety of molecules, especially cytokines. The inflammatory cytokine, TNF-like ligand 1A (TL1A), has been reported as an inflammation stimulator in-multiple autoimmune diseases. Here, we studied the effects of TL1A/TNF-receptor 2 (TNFR2) pathway on the therapeutic potency of bone marrow-derived MSCs (BMSCs).

Global transcriptome study of Dip2B-deficient mouse embryonic lung fibroblast reveals its important roles in cell proliferation and development.

Disco-interacting protein 2 homolog B (Dip2B) is a member of Dip2 family encoded by gene. Dip2B has been reported to regulate murine epithelial KIT progenitor cell expansion and differentiation epigenetically via exosomal miRNA targeting during salivary gland organogenesis. However, its molecular functions, cellular activities and biological process remain unstudied.

Cinnamaldehyde protects against rat intestinal ischemia/reperfusion injuries by synergistic inhibition of NF-κB and p53.

Our preliminary study shows that cinnamaldehyde (CA) could protect against intestinal ischemia/reperfusion (I/R) injuries, in which p53 and NF-κB p65 play a synergistic role. In this study, we conducted in vivo and in vitro experiments to verify this proposal. SD rats were pretreated with CA (10 or 40 mg · kg · d, ig) for 3 days, then subjected to 1 h mesenteric ischemia followed by 2 h reperfusion.

Indian Hedgehog regulates senescence in bone marrow-derived mesenchymal stem cell through modulation of ROS/mTOR/4EBP1, p70S6K1/2 pathway.

Premature senescence of bone marrow-derived mesenchymal stem cells (BMSC) remains a major concern for their application clinically. Hedgehog signaling has been reported to regulate aging-associated markers and MSC skewed differentiation. Indian Hedgehog (IHH) is a ligand of Hedgehog intracellular pathway considered as an inducer in chondrogenesis of human BMSC.

Aquaporin 5 promotes tumor migration and angiogenesis in non-small cell lung cancer cell line H1299.

Non-small cell lung cancer (NSCLC) constitutes the majority of all lung-cancer cases. Aquaporin 5 (AQP5) may be involved in NSCLC by promoting lung-cancer initiation and progression. The present study aimed to determine the role of AQP5 in migration and angiogenesis using NSCLC cells and HUVECs.

TL1A/TNFR2-mediated mitochondrial dysfunction of fibroblast-like synoviocytes increases inflammatory response in patients with rheumatoid arthritis via reactive oxygen species generation.

Rheumatoid arthritis (RA) is the major autoimmune destructive disease of joints with a complicated pathogenesis. The contribution of tumor necrosis factor-like ligand 1A (TL1A) in RA pathogenesis, especially on fibroblast-like synoviocytes (FLS), has been suggested clinically. The present study investigated the role of TL1A in mitochondrial dysfunction, induced oxidative stress in mitochondria, apoptosis resistance and the inflammatory response in FLS obtained from RA patients (RA-FLS).

Protection of diabetes-induced kidney injury by phosphocreatine via the regulation of ERK/Nrf2/HO-1 signaling pathway.

Diabetic nephropathy is the most common long-term complication of diabetes mellitus. The Methylglyoxal (MGO) production is mainly by metabolic pathways, such as lipolysis and glycolysis, its increases in the DM enhances oxidative stress and plays a crucial role in the diabetic nephrotic pathogenesis. Phosphocreatine (PCr) can improve lipopolysaccharide, ox-LDL-induced atherosclerosis, and alleviate vascular endothelial cell injury in diabetes.

Phosphocreatine Improves Cardiac Dysfunction by Normalizing Mitochondrial Respiratory Function through JAK2/STAT3 Signaling Pathway and .

Diabetic cardiomyopathy (DCM) is one of the common cardiovascular complications in patients with diabetes. Accumulating evidence has demonstrated that DCM is thoroughly related to mitochondrial energy impairment and increases the generation of reactive oxygen species (ROS). Therefore, an ongoing study is developing strategies to protect cardiac mitochondria from diabetic complications, especially from hyperglycemia.