Enhanced machine learning models for predicting one-year mortality in individuals suffering from type A aortic dissection.

Objective: The study objective was to develop and validate an interpretable machine learning model to predict 1-year mortality in patients with type A aortic dissection, improving risk classification and aiding clinical decision-making.

Methods: We enrolled 289 patients with type A aortic dissection, dividing them into a training cohort (202 patients) and a validation cohort (87 patients). The Least Absolute Shrinkage and Selection Operator method with 10-fold cross-validation identified 8 key factors related to 1-year mortality.

RP105 Attenuates Ischemia/Reperfusion-Induced Oxidative Stress in the Myocardium via Activation of the Lyn/Syk/STAT3 Signaling Pathway.

Although our previous studies have established the crucial role of RP105 in myocardial ischemia/reperfusion injury (MI/RI), its involvement in regulating oxidative stress induced by MI/RI remains unclear. To investigate this, we conducted experiments using a rat model of ischemia/reperfusion (I/R) injury. Adenovirus carrying RP105 was injected apically at multiple points, and after 72 h, the left anterior descending coronary artery was ligated for 30 min followed by 2 h of reperfusion.

The emerging role of DOT1L in cell proliferation and differentiation: Friend or foe.

Cell proliferation and differentiation are the basic physiological activities of cells. Mistakes in these processes may affect cell survival, or cause cell cycle dysregulation, such as tumorigenesis, birth defects and degenerative diseases. In recent years, it has been found that histone methyltransferase DOT1L is the only H3 lysine 79 methyltransferase, which plays an important role in the process of cell fate determination through monomethylation, dimethylation and trimethylation of H3K79.

The mechanism of the NFAT transcription factor family involved in oxidative stress response.

As a transcriptional activator widely expressed in various tissues, nuclear factor of activated T cells (NFAT) is involved in the regulation of the immune system, the development of the heart and brain systems, and classically mediating pathological processes such as cardiac hypertrophy. Oxidative stress is an imbalance of intracellular redox status, characterized by excessive generation of reactive oxygen species, accompanied by mitochondrial dysfunction, calcium overload, and subsequent lipid peroxidation, inflammation, and apoptosis. Oxidative stress occurs during various pathological processes, such as chronic hypoxia, vascular smooth muscle cell phenotype switching, ischemia-reperfusion, and cardiac remodeling.

Research progress of B subfamily of leucocyte immunoglobulin-like receptors in inflammation.

Leucocyte immunoglobulin-like receptors subfamily B (LILRB) belongs to the type I transmembrane glycoproteins, which is the immunosuppressive receptor. LILRBs are widely expressed in bone marrow cells, hematopoietic stem cells, nerve cells and other body cells. Studies have found that LILRBs receptor can bind to a variety of ligands and has a variety of biological functions such as regulating inflammatory response, immune tolerance and cell differentiation.

Farnesylthiosalicylic Acid-Loaded Albumin Nanoparticle Alleviates Renal Fibrosis by Inhibiting Ras/Raf1/p38 Signaling Pathway.

Background: Renal fibrosis is the common pathway in chronic kidney diseases progression to end-stage renal disease, but to date, no clinical drug for its treatment is approved. It has been demonstrated that the inhibitor of proto-oncogene Ras, farnesylthiosalicylic acid (FTS), shows therapeutic potential for renal fibrosis, but its application was hindered by the water-insolubility and low bioavailability. Hence, in this study, we improved these properties of FTS by encapsulating it into bovine serum albumin nanoparticles (AN-FTS) and tested its therapeutic effect in renal fibrosis.

Canagliflozin Facilitates Reverse Cholesterol Transport Through Activation of AMPK/ABC Transporter Pathway.

Background And Purpose: Cholesterol is an essential lipid and its homeostasis is a major factor for many diseases, such as hyperlipidemia, atherosclerosis, diabetes, and obesity. Sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin (Cana) is a new kind of hypoglycemic agent, which decreases urinary glucose reabsorption and reduces hyperglycemia. Cana has been shown to regulate serum lipid, decrease serum triglyceride and increase serum high-density lipoprotein-cholesterol (HDL-C), and improve cardiovascular outcomes.

Hepatocyte-specific deletion of Nlrp6 in mice exacerbates the development of non-alcoholic steatohepatitis.

Objective: Previous studies have established that deficiency in Nucleotide-binding and oligomerization domain (NOD)-like receptor family pyrin domain containing 6 (Nlrp6) changes the configuration of the gut microbiota, which leads to hepatic steatosis. Here, we aimed to determine the hepatic function of Nlrp6 in lipid metabolism and inflammation and its role in the development of non-alcoholic steatohepatitis (NASH).

Methods: Nlrp6 and hepatocyte-specific Nlrp6-knockout mice were fed a high-fat diet (HFD) or methionine-choline deficient (MCD) diet to induce fatty liver or steatohepatitis, respectively.

Feeding-induced hepatokine, Manf, ameliorates diet-induced obesity by promoting adipose browning via p38 MAPK pathway.

Activating beige adipocytes in white adipose tissue (WAT) to increase energy expenditure is a promising strategy to combat obesity. We identified that mesencephalic astrocyte-derived neurotrophic factor (Manf) is a feeding-induced hepatokine. Liver-specific Manf overexpression protected mice against high-fat diet-induced obesity and promoted browning of inguinal subcutaneous WAT (iWAT).

Blocking 5-LO pathway alleviates renal fibrosis by inhibiting the epithelial-mesenchymal transition.

The enzyme 5-lipoxygenase (5-LO) converts arachidonic acid to leukotrienes, which mediate inflammation. The enzyme is known to contribute to organ fibrosis, but how it contributes to renal fibrosis is unclear. Here, we reported that fibrotic kidneys expressed high levels of 5-LO, and deleting the 5-LO gene mitigated renal fibrosis in mice subjected to unilateral ureteral obstruction (UUO), based on assays of collagen deposition, injury and inflammation.

Mesencephalic astrocyte-derived neurotrophic factor alleviates alcohol induced hepatic steatosis via activating Stat3-mediated autophagy.

Alcoholic fatty liver disease (AFLD) is induced by alcohol consumption and may progress to more severe liver diseases such as alcoholic steatohepatitis, fibrosis and cirrhosis, and even hepatocellular carcinoma. Mesencephalic astrocyte-derived neurotrophic factor (MANF) participates in maintaining lipid homeostasis. However, the role of MANF in the pathogenesis of AFLD remains unclear.

Sirtuin 6 supra-physiological overexpression in hypothalamic pro-opiomelanocortin neurons promotes obesity via the hypothalamus-adipose axis.

Sirtuin 6 (Sirt6), a member of the Sirtuin family, has important roles in maintaining glucose and lipid metabolism. Our previous studies demonstrated that the deletion of Sirt6 in pro-opiomelanocortin (POMC)-expressing cells by the loxP-Cre system resulted in severe obesity and hepatic steatosis. However, whether overexpression of Sirt6 in hypothalamic POMC neurons could ameliorate diet-induced obesity is still unknown.

Glucagon-like peptide 1 analogue prevents cholesterol gallstone formation by modulating intestinal farnesoid X receptor activity.

Background & Aims: Cholesterol gallstone disease (CGD) is a common gastrointestinal disease. Liraglutide, an analogue of glucagon-like peptide 1, has been approved to treat type 2 diabetes. Clinical studies have suggested a potential role of liraglutide in CGD.

Targeting Interstitial Myofibroblast-Expressed Integrin αvβ3 Alleviates Renal Fibrosis.

Renal fibrosis is the final manifestation of various chronic kidney diseases. Interstitial myofibroblasts, which are reported to highly express integrin αvβ3, are the effector cells in renal fibrogenesis. Since current therapies do not efficiently target these cells, there is no effective therapeutic method for preventing or mitigating the disease.

SB431542-Loaded Liposomes Alleviate Liver Fibrosis by Suppressing TGF-β Signaling.

Liver fibrosis is a common outcome of most chronic liver diseases, but there is no clinically approved drug for its treatment. Previous studies have reported the potential of SB431542 as an inhibitor of TGF-β signaling in the treatment of liver fibrosis, but it shows poor water solubility and low bioavailability. Here, we improve these characteristics of SB431542 by loading it into liposomes (SB-Lips) with two FDA-approved excipients: soya phosphatidyl S100 and Solutol HS15.

The diabetes medication canagliflozin promotes mitochondrial remodelling of adipocyte via the AMPK-Sirt1-Pgc-1α signalling pathway.

Unlabelled: The diabetes medication canagliflozin (Cana) is a sodium glucose cotransporter 2 (SGLT2) inhibitor acting by increasing urinary glucose excretion and thus reducing hyperglycaemia. Cana treatment also reduces body weight. However, it remains unclear whether Cana could directly work on adipose tissue.

Adductor canal block combined with local infiltration analgesia versus isolated adductor canal block in reducing pain and opioid consumption after total knee arthroplasty: a systematic review and meta-analysis.

Objective: To evaluate the efficacy and safety of the addition of local infiltration analgesia (LIA) to adductor canal block (ACB) for pain control after primary total knee arthroplasty (TKA).

Methods: Two reviewers independently searched for potentially relevant published studies using electronic databases, including PubMed® (1966 to June 2019), Embase® (1974 to June 2019) and Web of Science (1990 to June 2019). The results were pooled using the random-effects model to produce standard mean differences for continuous outcome data and odds ratio for categorical outcome data.

Sirt6 Alleviated Liver Fibrosis by Deacetylating Conserved Lysine 54 on Smad2 in Hepatic Stellate Cells.

Backgrounds And Aims: Activation of hepatic stellate cells (HSCs) is a central driver of fibrosis. This study aimed to elucidate the role of the deacetylase sirtuin 6 (Sirt6) in HSC activation and liver fibrosis.

Approach And Results: Gain-of-function and loss-of-function models were used to study the function of Sirt6 in HSC activation.

Sirt6 in pro-opiomelanocortin neurons controls energy metabolism by modulating leptin signaling.

Objective: Sirt6 is an essential regulator of energy metabolism in multiple peripheral tissues. However, the direct role of Sirt6 in the hypothalamus, specifically pro-opiomelanocortin (POMC) neurons, controlling energy balance has not been established. Here, we aimed to determine the role of Sirt6 in hypothalamic POMC neurons in the regulation of energy balance and the underlying mechanisms.

Telmisartan attenuates obesity-induced insulin resistance via suppression of AMPK mediated ER stress.

Telmisartan is a known angiotensin II (Ang II) AT1 receptor blocker (ARB). While the beneficial effect of Telmisartan on glucose and lipid metabolism has been reported, the underlying molecular mechanism remained unclear. The endoplasmic reticulum (ER) stress is considered as one of important factors contributing to insulin resistance.

Targeted delivery of celastrol to renal interstitial myofibroblasts using fibronectin-binding liposomes attenuates renal fibrosis and reduces systemic toxicity.

Renal fibrosis often occurs in chronic kidney disease, and effective treatment is needed. Celastrol (CEL) may attenuate renal fibrosis, but it distributes throughout the body, leading to severe systemic toxicities. Here we designed a system to deliver CEL specifically to interstitial myofibroblasts, which is a key driver of renal fibrogenesis.

Montelukast Prevents Mice Against Acetaminophen-Induced Liver Injury.

Acetaminophen (APAP) is a widely used over-the-counter antipyretic and analgesic drug. Overdose of APAP is the leading cause of hospital admission for acute liver failure. Montelukast is an antagonist of cysteinyl leukotriene receptor 1 (Cysltr1), which protects from inflammation and oxidative stress.

A896G and C1196T Polymorphisms Within the TLR4 Gene Abate Toll-Like Receptor 4-Mediated Signaling in HepG2 Cells.

Toll-like receptor 4 (TLR4) appears to play an important role in the development and progression of hepatocellular carcinoma (HCC), but it is unclear whether single-nucleotide polymorphisms (SNPs) in the TLR4 gene influence HCC. In this study, we investigated the effects of TLR4 SNPs on HepG2 cell survival and proliferation, migration, and invasion. Plasmids carrying wild-type or mutant versions of the TLR4 gene (A896G and/or C1196T) were stably transfected into HepG2 cells, and cell viability and proliferation were analyzed using the Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays, whereas apoptosis was assessed using flow cytometry.

Advances in ultrasound-targeted microbubble-mediated gene therapy for liver fibrosis.

Hepatic fibrosis develops as a wound-healing scar in response to acute and chronic liver inflammation and can lead to cirrhosis in patients with chronic hepatitis B and C. The condition arises due to increased synthesis and reduced degradation of extracellular matrix (ECM) and is a common pathological sequela of chronic liver disease. Excessive deposition of ECM in the liver causes liver dysfunction, ascites, and eventually upper gastrointestinal bleeding as well as a series of complications.