Insights on exploring the therapeutic potential and structural modification of Tetrandrine.

Tetrandrine (Tet), a bisbenzylisoquinoline alkaloid from , is noted for its diverse pharmacological effects but faces limitations in clinical use due to toxicity, poor solubility, and low bioavailability. Researchers are working to address these issues by developing Tet derivatives with greater therapeutic potential through structural modification. Generally, key modifications include: 1) introducing an aromatic heterocycle or a hydrophobic alkyne unit at the -5 position can enhance its antitumor activity; 2) adding an amide, sulfonamide, or electron-withdrawing group at the -14 position can enhance its antitumor activity; 3) changing its structure to a quaternary ammonium salt can alter its solubility and greatly boost its antibacterial activity; 4) structural modification of the -12-methoxybenzyl motif can enhance its metabolic stability and thus change the activity of the analogs; 5) Tet structural simplification may result in the identification of anticancer lead compounds with novel mechanisms of action.

Evaluation of mavacamten in patients with hypertrophic cardiomyopathy.

Aims: We aimed to comprehensively assess the safety and efficacy of mavacamten in hypertrophic cardiomyopathy (HCM) patients.

Methods: A systematic review and meta-analysis was conducted, and efficacy [changes in postexercise left ventricular outflow tract (LVOT) gradient, left ventricular ejection fraction (LVEF), peak oxygen consumption (pVO 2 ), Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS), and the proportion of patients exhibiting an improvement of at least one New York Heart Association (NYHA) functional class from baseline)], safety (total count of treatment-emergent adverse events and SAEs, as well as the proportion of patients experiencing at least one adverse event or SAE), and cardiac biomarkers (NT-proBNP and cTnI) outcomes were evaluated.

Results: We incorporated data from four randomized controlled trials, namely EXPLORER-HCM, VALOR-HCM, MAVERICK-HCM, and EXPLORER-CN.

LINC00173 silence and estrone supply suppress ER breast cancer by estrogen receptor α degradation and LITAF activation.

Persistent activation of estrogen receptor alpha (ERα)-mediated estrogen signaling plays a pivotal role in driving the progression of estrogen receptor positive (ER) breast cancer (BC). In the current study, LINC00173, a long non-coding RNA, was found to bind both ERα and lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNFα) factor (LITAF), then cooperatively to inhibit ERα protein degradation by impeding the nuclear export of ERα. Concurrently, LITAF was found to attenuate TNFα transcription after binding to LINC00173, and this attenuating transcriptional effect was quite significant under lipopolysaccharide stimulation.

Effect of ubiquinol on electrophysiology during high-altitude acclimatization and de-acclimatization: A substudy of the Shigatse CARdiorespiratory fitness (SCARF) randomized clinical trial.

Background: High-altitude exposure changes the electrical conduction of the heart. However, reports on electrocardiogram (ECG) characteristics and potent prophylactic agents during high-altitude acclimatization and de-acclimatization are inadequate. This study aimed to investigate the effects of ubiquinol on electrophysiology after high-altitude hypoxia and reoxygenation.

Postmarketing Safety of Sacituzumab Govitecan: A Pharmacovigilance Study Based on the FDA Adverse Event Reporting System.

Sacituzumab govitecan is widely used for the treatment of breast cancer and urothelial carcinoma, but available information regarding adverse events (AEs) is limited. We aim to explore the AE induced by sacituzumab govitecan by mining the FDA Adverse Event Reporting System (FAERS) database. The association between sacituzumab govitecan and AEs was evaluated using the information component.

Sulfur mustard analog 2-chloroethyl ethyl sulfide increases triglycerides by activating DGAT1-dependent biogenesis and inhibiting PGC1ɑ-dependent fat catabolism in immortalized human bronchial epithelial cells.

Using sulfur mustard analog 2-chloroethyl ethyl sulfide (CEES), we established an model by poisoning cultured immortalized human bronchial epithelial cells. Nile Red staining revealed lipids accumulated 24 h after a toxic dose of CEES (0.9 mM).

GSK3β mediates the spatiotemporal dynamics of NLRP3 inflammasome activation.

Subcellular machinery of NLRP3 is essential for inflammasome assembly and activation. However, the stepwise process and mechanistic basis of NLRP3 engagement with organelles remain unclear. Herein, we demonstrated glycogen synthase kinase 3β (GSK3β) as a molecular determinant for the spatiotemporal dynamics of NLRP3 inflammasome activation.

Exploration of Potential Integrated Models of N6-Methyladenosine Immunity in Systemic Lupus Erythematosus by Bioinformatic Analyses.

Systemic lupus erythematosus (SLE) is a prototypical systemic autoimmune disease of unknown etiology. The epigenetic regulation of N6-methyladenosine (m6A) modification in immunity is emerging. However, few studies have focused on SLE and m6A immune regulation.

N6-methyladenosine-dependent modification of circGARS acts as a new player that promotes SLE progression through the NF-κB/A20 axis.

Background: Certain circRNAs could be used as biomarkers to determine the risk of development and/or severity of systemic lupus erythematosus, and their new function in the regulation of gene expression has motivated us to investigate their role in SLE METHODS: Experimental methods including qRT-PCR, RNA immunoprecipitation (RIP), pulldown, dual luciferase reporter assay, RNA interference and cell transfection, RNA fluorescence in situ hybridization, western blotting, and mass spectrometry were used to assessed circGARS (hsa_circRNA_0009000) for immune functions and defined mechanisms by which circGARS promotes the progression in SLE.

Results: Our results demonstrated that the levels of circGARS was remarkably upregulated in SLE and correlated with clinicopathological features. CircGARS directly combined with microRNA-19a (miR-19a).

Screening for Active Compounds Targeting Human Natural Killer Cell Activation Identifying Daphnetin as an Enhancer for IFN-γ Production and Direct Cytotoxicity.

Natural killer (NK) cells are a potent weapon against tumor and viral infection. Finding active compounds with the capacity of enhancing NK cell effector functions will be effective to develop new anti-cancer drugs. In this study, we initially screened 287 commercially available active compounds by co-culturing with peripheral blood mononuclear cells (PBMCs).

C3/C3aR inhibition alleviates GMH-IVH-induced hydrocephalus by preventing microglia-astrocyte interactions in neonatal rats.

Activation of microglia and astrocytes following germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH) plays a detrimental role in posthemorrhagic hydrocephalus (PHH). It is still unclear whether or how an interaction occurs between microglia and astrocytes in PHH. Here, we investigated the role of the C3/C3aR pathway in microglia and astrocyte interactions and whether C3/C3aR-targeted inhibition could alleviate PHH following GMH-IVH.

Risk factors for incomplete thrombosis in false lumen in sub-acute type B aortic dissection post-TEVAR.

There is scarce information about the risk factors for incomplete false lumen thrombosis (FLT) among type B aortic dissection (AD) patients, particularly in the sub-acute phase following thoracic endovascular aortic repair (TEVAR). We enrolled consecutive sub-acute type B AD patients at Xinqiao Hospital (Chongqing, China) from May 2010 to December 2019. Patients with severe heart failure, cancer, and myocardial infarction were excluded.

Modulation of Perturbed Cardiac Metabolism in Rats Under High-Altitude Hypoxia by Combination Treatment With L-carnitine and Trimetazidine.

High-altitude hypoxia has long been recognized as a vital etiology for high-altitude illnesses. High-altitude myocardial injury (HAMI) usually occurs in people who suffered from high-altitude exposure. To date, the molecular mechanism of HAMI remains elusive, which seriously hinders the prevention and treatment of HAMI.

N-methyladenosine (mA) in pancreatic cancer: Regulatory mechanisms and future direction.

N-methyladenosine (mA), the most abundant RNA modification in eukaryotes, plays a pivotal role in regulating many cellular and biological processes. Aberrant mA modification has recently been involved in carcinogenesis in various cancers, including pancreatic cancer. Pancreatic cancer is one of the deadliest cancers.

Quantitative Profiling of Oxylipins in Acute Experimental Intracerebral Hemorrhage.

Oxylipins are a series of bioactive lipid metabolites derived from polyunsaturated fatty acids that are involved in cerebral homeostasis and the development of intracerebral hemorrhage (ICH). However, comprehensive quantification of the oxylipin profile in ICH remains unknown. Therefore, an ICH mouse model was constructed and liquid chromatography tandem mass spectrometry was then performed to quantify the change in oxylipins in ICH.

Consensus recommendations of three-dimensional visualization for diagnosis and management of liver diseases.

Three-dimensional (3D) visualization involves feature extraction and 3D reconstruction of CT images using a computer processing technology. It is a tool for displaying, describing, and interpreting 3D anatomy and morphological features of organs, thus providing intuitive, stereoscopic, and accurate methods for clinical decision-making. It has played an increasingly significant role in the diagnosis and management of liver diseases.

Kinsenoside ameliorates intervertebral disc degeneration through the activation of AKT-ERK1/2-Nrf2 signaling pathway.

Intervertebral disc degeneration (IDD) is recognized as the major contributor to low back pain, which results in disability worldwide and heavy burdens on society and economy. Here we present evidence that the lower level of Nrf2 is closely associated with higher grade of IDD. The apoptosis and senescence of nucleus pulposus cells (NPCs) were exacerbated by Nrf2 knockdown, but suppressed by Nrf2 overexpression under oxidative stress.

A novel photoelectrochemical strategy based on an integrative photoactive heterojunction nanomaterial and a redox cycling amplification system for ultrasensitive determination of microRNA in cells.

An ultrasensitive photoelectrochemical (PEC) bioassay for determination of microRNA was proposed based on an integrative photoactive heterojunction nanomaterial to provide the basis of excellent PEC responses and an efficient redox cycling amplification system to improve the detection performances. To establish the bioassay system, the biosensor was firstly modified with BiWO@BiS and alkaline phosphatase (ALP). The detection solution was composed of ascorbic acid phosphate (AAP) and ferrocenecarboxylic acid (FcA), where ALP converted AAP into ascorbic acid (AA) to trigger a process of redox cycling amplification by reducing FcA to FcA, resulting in enhanced photocurrent responses of BiWO@BiS.

Abietic acid suppresses non-small-cell lung cancer cell growth via blocking IKKβ/NF-κB signaling.

Abietic acid (AA) is one of the terpenoids, which are multifunctional natural compounds. It has been reported that AA possesses favorable therapeutic effects on inflammation and obesity. In the present study, we determined the inhibitory effect of AA on the proliferation and growth of non-small-cell lung cancer (NSCLC) cell lines for the first time.