Small-molecule-induced ERBB4 activation to treat heart failure.

Heart failure is a common and deadly disease requiring new treatments. The neuregulin-1/ERBB4 pathway offers cardioprotective benefits, but using recombinant neuregulin-1 as therapy has limitations due to the need for intravenous delivery and lack of receptor specificity. We hypothesize that small-molecule activation of ERBB4 could protect against heart damage and fibrosis.

ZIF-8 as efficient carriers for polysaccharide from Tetrastigma Hemsleyanum Diels et Gilg in acute lung injury induced by lipopolysaccharides.

Acute lung injury (ALI) is a critical respiratory syndrome significantly impacting patient health. Tetrastigma hemsleyanum Diels et Gilg (Sanyeqing, SYQ) is a traditional Chinese medicine and its polysaccharides (SYQP) have demonstrated efficacy in counteracting lipopolysaccharide-induced ALI. This study characterized the structure of SYQP and synthesized the SYQP@ZIF-8 composite using biomimetic mineralization, evaluating encapsulation and release efficiency.

Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo.

Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw MRI data were shared from international samples ( = 1,384) of medication-free individuals with first-episode and recurrent MDD ( = 685) in a current depressive episode of at least moderate severity, but not treatment-resistant depression, as well as healthy controls ( = 699).

Melting entropy of crystals determined by electron-beam-induced configurational disordering.

Upon melting, the molecules in a crystal explore numerous configurations, reflecting an increase in disorder. The molar entropy of disorder can be defined by Boltzmann's formula Δ = ln(), where is the increase in the number of microscopic states, so far inaccessible experimentally. We found that the Arrhenius frequency factor of the electron diffraction signal decay provides through an experimental equation = , where is an inelastic scattering cross section.

Effectiveness and safety of ivabradine in Chinese patients with chronic heart failure: an observational study.

Aims: A therapeutic strategy for chronic heart failure (HF) is to lower resting heart rate (HR). Ivabradine is a well-known HR-lowering agent, but limited prospective data exist regarding its use in Chinese patients. This study aimed to evaluate the effectiveness and safety of ivabradine in Chinese patients with chronic HF.

Guben Qingfei decoction attenuates LPS-induced acute lung injury by modulating the TLR4/NF-κB and Keap1/Nrf2 signaling pathways.

Ethnopharmacological Relevance: Acute lung injury (ALI) is a life-threatening and widespread disease, with exceptionally high morbidity and mortality rates. Unfortunately, effective drugs for ALI treatment are currently lacking. Guben Qingfei decoction (GBQF) is a Chinese herbal compound known for its efficacy in treating viral pneumonia, yet the precise underlying mechanisms remain unknown.

A robust yeast biocontainment system with two-layered regulation switch dependent on unnatural amino acid.

Synthetic auxotrophy in which cell viability depends on the presence of an unnatural amino acid (unAA) provides a powerful strategy to restrict unwanted propagation of genetically modified organisms (GMOs) in open environments and potentially prevent industrial espionage. Here, we describe a generic approach for robust biocontainment of budding yeast dependent on unAA. By understanding escape mechanisms, we specifically optimize our strategies by introducing designed "immunity" to the generation of amber-suppressor tRNAs and developing the transcriptional- and translational-based biocontainment switch.

Development of constitutively synergistic nanoformulations to enhance chemosensitivity in T-cell leukemia.

Advances in multiagent chemotherapy have led to recent improvements in survival for patients with acute lymphoblastic leukemia (ALL); however, a significant fraction do not respond to frontline chemotherapy or later relapse with recurrent disease, after which long-term survival rates remain low. To develop new, effective treatment options for these patients, we conducted a series of high-throughput combination drug screens to identify chemotherapies that synergize in a lineage-specific manner with MRX-2843, a small molecule dual MERTK and FLT3 kinase inhibitor currently in clinical testing for treatment of relapsed/refractory leukemias and solid tumors. Using experimental and computational approaches, we found that MRX-2843 synergized strongly-and in a ratio-dependent manner-with vincristine to inhibit both B-ALL and T-ALL cell line expansion.

New Loss-of-Function Mutations in PCSK9 Reduce Plasma LDL Cholesterol.

Background: Lower plasma levels of LDL (low-density lipoprotein) cholesterol (LDL-C) can reduce the risk of atherosclerotic cardiovascular disease. The loss-of-function mutations in (proprotein convertase subtilisin/kexin type 9) have been known to associate with low LDL-C in many human populations. PCSK9 genetic variants in Chinese Uyghurs who are at high risk of atherosclerotic cardiovascular disease due to their dietary habits have not been reported.

Polysaccharides from Tetrastigma Hemsleyanum Diels et Gilg attenuate LPS-induced acute lung injury by modulating TLR4/COX-2/NF-κB signaling pathway.

Tetrastigma Hemsleyanum Diels et Gilg (Sanyeqing, SYQ), a traditional herb native to China, has been widely used in the treatment of inflammatory diseases, febrile convulsions and dysentery. Previous studies have demonstrated the hypoglycemic, anti-inflammatory and anti-pyretic effects of polysaccharides from SYQ (SYQP). However, the role of SYQP in acute lung injury (ALI) remained unknown.

The therapeutic efficacy of resveratrol for acute lung injury-A meta-analysis of preclinical trials.

Resveratrol (RES) has a protective effect on acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Our purpose was to conduct a meta-analysis to investigate the efficacy of RES for ALI/ARDS in animal models. PubMed, EMBASE and Web of Science were searched to screen relevant preclinical trials.

Sinus Tachycardia: a Multidisciplinary Expert Focused Review.

Sinus tachycardia (ST) is ubiquitous, but its presence outside of normal physiological triggers in otherwise healthy individuals remains a commonly encountered phenomenon in medical practice. In many cases, ST can be readily explained by a current medical condition that precipitates an increase in the sinus rate, but ST at rest without physiological triggers may also represent a spectrum of normal. In other cases, ST may not have an easily explainable cause but may represent serious underlying pathology and can be associated with intolerable symptoms.

The Protective Effect of Sulodexide on Acute Lung Injury Induced by a Murine Model of Obstructive Jaundice.

Introduction: The effect of sulodexide (SLX) on obstructive jaundice- (OJ-) induced acute lung injury (ALI) in rats was examined in this study.

Methods: In this study, 48 rats were randomly assigned to one of six groups: sham, OJ, OJ+saline, OJ+SLX (0.5 mg/ml/d), OJ+SLX (1 mg/ml/d), and OJ+SLX (2 mg/ml/d).

Effect of epicatechin on inflammatory cytokines and MAPK/NF-κB signaling pathway in lipopolysaccharideinduced acute lung injury of BALB/c mice.

This study evaluated the anti-inflammatory effect of epicatechin (EC) on acute lung injury (ALI) induced by lipopolysaccharide (LPS) of tracheal installation in BALB/c mice. It was observed that EC could alleviate not only the histopathological changes but also decrease the wet/dry weight (W/D) ratio of lung tissues. It also suppressed the release of IL-1β, IL-6, and TNF-α in serum, bronchoalveolar lavage fluid (BALF), and lung tissues, respectively.

Taurine Alleviates LPS-Induced Acute Lung Injury by Suppressing TLR-4/NF-κB Pathway.

Taurine has the function of immune regulation, relieving acute and chronic inflammation caused by various agents, and maintaining cell homeostasis. This investigation focused on the protective functions of taurine targeting acute lung injury (ALI) induced by LPS. Sixty male SD rats aged 6-7 weeks were segregated at random: blank control group (C group), taurine control group (T group), ALI model group (LPS group), and taurine prevention groups (LPST1, LPST, LPST3 Groups).

Ethanol extracts of Rhaponticum uniflorum (L.) DC inflorescence ameliorate LPS-mediated acute lung injury by alleviating inflammatory responses via the Nrf2/HO-1 signaling pathway.

Ethnopharmacological Relevance: Rhaponticum uniflorum (L.) DC is a member of the Compositae family. Loulu flowers (LLF) is the inflorescence of this plant, which is a commonly used Mongolian medicine for the treatment of inflammatory diseases due to its heat-clearing and detoxifying properties.

Pharmacophore-Based Design of Phenyl-[hydroxycyclohexyl] Cycloalkyl-Carboxamide Mitofusin Activators with Improved Neuronal Activity.

Mitochondrial fragmentation from defective fusion or unopposed fission contributes to many neurodegenerative diseases. Small molecule mitofusin activators reverse mitochondrial fragmentation , promising a novel therapeutic approach. The first-in-class mitofusin activator, , has a short plasma and limited neurological system bioavailability, conferring "burst activation".

Immunogenicity and efficacy of mRNA COVID-19 vaccine MRT5500 in preclinical animal models.

Emergency use authorization of COVID vaccines has brought hope to mitigate pandemic of coronavirus disease 2019 (COVID-19). However, there remains a need for additional effective vaccines to meet the global demand and address the potential new viral variants. mRNA technologies offer an expeditious path alternative to traditional vaccine approaches.

The splicing factor SRSF1 stabilizes the mRNA of TSLP to enhance acute lung injury.

Acute lung injury (ALI) is a severe disease with a high rate of morbidity and mortality, characterized by excessive and uncontrolled inflammatory response in lung. Recent studies demonstrated that serine arginine-rich splicing factor 1 (SRSF1) is involved in inflammation. However, whether SRSF1 modulates ALI remains to be determined.

Overexpression of Limb Bud and Heart Alleviates Sepsis-Induced Acute Lung Injury via Inhibiting the NLRP3 Inflammasome.

Objective: Sepsis is a leading cause of acute lung injury (ALI). This study attempted to investigate the effects of limb bud and heart (LBH) on the development of sepsis-induced ALI and its underlying mechanism of action.

Methods: The sepsis-induced ALI mouse model was established by cecal ligation and puncture (CLP).

Association Between β-Blocker Use and Mortality/Morbidity in Patients With Heart Failure With Reduced, Midrange, and Preserved Ejection Fraction and Advanced Chronic Kidney Disease.

Background: It is unknown if β-blockers reduce mortality/morbidity in patients with heart failure (HF) and advanced chronic kidney disease (CKD), a population underrepresented in HF trials.

Methods: Observational cohort of HF patients with advanced CKD (estimated glomerular filtration rate <30 mL/min per 1.73 m) from the Swedish Heart Failure Registry between 2001 and 2016.

Distinguishing Extravascular from Intravascular Ferumoxytol Pools within the Brain: Proof of Concept in Patients with Treated Glioblastoma.

Background And Purpose: Glioblastoma-associated macrophages are a major constituent of the immune response to therapy and are known to engulf the iron-based MR imaging contrast agent, ferumoxytol. Current ferumoxytol MR imaging techniques for localizing macrophages are confounded by contaminating intravascular signal. The aim of this study was to assess the utility of a newly developed MR imaging technique, segregation and extravascular localization of ferumoxytol imaging, for differentiating extravascular-from-intravascular ferumoxytol contrast signal at a delayed 24-hour imaging time point.