Dual targeting and bioresponsive nano-PROTAC induced precise and effective lung cancer therapy.

Epigenetic regulation has emerged as a promising therapeutic strategy for lung cancer treatment, which can facilitate the antitumor responses by modulating epigenetic dysregulation of target proteins in lung cancer. The proteolysis-targeting chimera (PROTAC) reagent, dBET6 shows effective inhibition of bromodomain-containing protein 4 (BRD4) that exerts antitumor efficacy by degrading BRD4 via the ubiquitin-proteasome system. Nevertheless, the low tissue specificity and bioavailability impede its therapeutic effects and clinical translation on lung cancer treatment.

Liver-Specific Ionizable Lipid Nanoparticles Mediated Efficient RNA Interference to Clear "Bad Cholesterol".

Background: High-level low-density lipoprotein cholesterol (LDL-C) plays a vital role in the development of atherosclerotic cardiovascular disease. Low-density lipoprotein receptors (LDLRs) are scavengers that bind to LDL-C in the liver. LDLR proteins are regulated by proprotein convertase subtilisin/kexin type 9 (PCSK9), which mediates the degradation of LDLR and adjusts the level of the plasma LDL-C.

Bioinspired PROTAC-induced macrophage fate determination alleviates atherosclerosis.

Atherosclerosis is a major cause of death and disability in cardiovascular disease. Atherosclerosis associated with lipid accumulation and chronic inflammation leads to plaques formation in arterial walls and luminal stenosis in carotid arteries. Current approaches such as surgery or treatment with statins encounter big challenges in curing atherosclerosis plaque.

A zwitterionic polymer-inspired material mediated efficient CRISPR-Cas9 gene editing.

The type II prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR/Cas9) adaptive immune system is a cutting-edge genome-editing toolbox. However, its applications are still limited by its inefficient transduction. Herein, we present a novel gene vector, the zwitterionic polymer-inspired material with branched structure (ZEBRA) for efficient CRISPR/Cas9 delivery.

The reversion of DNA methylation-induced miRNA silence via biomimetic nanoparticles-mediated gene delivery for efficient lung adenocarcinoma therapy.

Background: Lung cancer is one of the fatal cancers worldwide, and over 60% of patients are lung adenocarcinoma (LUAD). Our clinical data demonstrated that DNA methylation of the promoter region of miR-126-3p was upregulated, which led to the decreased expression of miR-126-3p in 67 cases of lung cancer tissues, implying that miR-126-3p acted as a tumor suppressor. Transduction of miR-126-3p is a potential therapeutic strategy for treating LUAD, yet the physiological environment and properties of miRNA challenge current transduction approaches.

Biomimetic metal-organic frameworks navigated biological bombs for efficient lung cancer therapy.

The rising risk of lung cancer has become a primary global concern with high mortality and mobility. Presently, clinically used anticancer drugs show limited efficacy and significant side effects. A new generation of anticancer weapons is in great demand for lung cancer therapy.

Promoter methylation-regulated miR-148a-3p inhibits lung adenocarcinoma (LUAD) progression by targeting MAP3K9.

Lung adenocarcinoma (LUAD) characterized by high metastasis and mortality is the leading subtype of non-small cell lung cancer. Evidence shows that some microRNAs (miRNAs) may act as oncogenes or tumor suppressor genes, leading to malignant tumor occurrence and progression. To better understand the molecular mechanism associated with miRNA methylation in LUAD progression and clinical outcomes, we investigated the correlation between miR-148a-3p methylation and the clinical features of LUAD.

Efficient Photoacoustic Imaging With Biomimetic Mesoporous Silica-Based Nanoparticles.

Indocyanine green (ICG), a near-infrared (NIR) fluorescent dye approved by the Food and Drug Administration (FDA), has been extensively used as a photoacoustic (PA) probe for PA imaging. However, its practical application is limited by poor photostability in water, rapid body clearance, and non-specificity. Herein, we fabricated a novel biomimetic nanoprobe by coating ICG-loaded mesoporous silica nanoparticles with the cancer cell membrane (namely, CMI) for PA imaging.

Electronic Properties of Armchair Black Phosphorene Nanoribbons Edge-Modified by Transition Elements V, Cr, and Mn.

The structural, electrical, and magnetic properties of armchair black phosphorene nanoribbons (APNRs) edge-functionalized by transitional metal (TM) elements V, Cr, and Mn were studied by the density functional theory combined with the non-equilibrium Green's function. Spin-polarized edge states introduce great varieties to the electronic structures of TM-APNRs. For APNRs with Mn-stitched edge, their band structures exhibit half-semiconductor electrical properties in the ferromagnetic state.

Renal denervation attenuates cardiac hypertrophy in spontaneously hypertensive rats via regulation of autophagy.

It has been suggested that renal denervation (RD) may attenuate left ventricular (LV) hypertrophy. However, the role that autophagy serves in this process is currently unclear. In the present study, utilizing a model of hypertension‑induced cardiac hypertrophy in spontaneous hypertensive rats, it was demonstrated that RD was significantly associated with a reduction in LV hypertrophy.

LC3B, a Protein That Serves as an Autophagic Marker, Modulates Angiotensin II-induced Myocardial Hypertrophy.

LC3B is a marker of autophagic activity, and growing evidence supports its importance in myocardial hypertrophy. Thus, regulating LC3B expression may provide an important avenue to inhibit autophagy and protect against or inhibit pathological myocardial hypertrophy. To address this question, we investigated the effects of altering LC3B mRNA expression and autophagic activity in the setting of cardiomyocyte hypertrophy.

Role of MiR-30a in cardiomyocyte autophagy induced by Angiotensin II.

Objective: The aim of this study was to investigate whether MiR-30a regulates autophagy by regulating the Beclin-1 protein, which is the marker for autophagosomes during myocardial injury, when induced by angiotensin II (Ang II).

Methods: We randomly assigned 20 rats into two equal groups: Control group and Ang II group. We detected the expression of MiR-30a by quantitative real-time polymerase chain reaction (RT-PCR), and we employed western blotting to detect the protein expression of Beclin-1.

HMGA1 is a new target of miR-195 involving isoprenaline-induced cardiomyocyte hypertrophy.

Emerging data have shown that microRNAs (miRNAs) have important functions in the processes of cardiac hypertrophy and heart failure that occur during the postnatal period. Cardiac overexpression of miR-195 results in pathological cardiac growth and heart failure in transgenic mice. In the present study, we analyzed the roles of miR-195 in cardiomyocyte hypertrophy and found that miR-195 was greatly upregulated during isoprenaline-induced cardiomyocyte hypertrophy.

miR-34a modulates angiotensin II-induced myocardial hypertrophy by direct inhibition of ATG9A expression and autophagic activity.

Cardiac hypertrophy is characterized by thickening myocardium and decreasing in heart chamber volume in response to mechanical or pathological stress, but the underlying molecular mechanisms remain to be defined. This study investigated altered miRNA expression and autophagic activity in pathogenesis of cardiac hypertrophy. A rat model of myocardial hypertrophy was used and confirmed by heart morphology, induction of cardiomyocyte autophagy, altered expression of autophagy-related ATG9A, LC3 II/I and p62 proteins, and decrease in miR-34a expression.