Prevent and Reverse Metabolic Dysfunction-Associated Steatohepatitis and Hepatic Fibrosis via mRNA-Mediated Liver-Specific Antibody Therapy.

Chronic exposure of the liver to multiple insults culminates in the development of metabolic dysfunctionassociated steatohepatitis (MASH), a complicated metabolic syndrome characterized by hepatic steatosis and inflammation, typically accompanied by progressive fibrosis. Despite extensive clinical evaluation, there remain challenges in MASH drug development, which are primarily due to unsatisfactory efficacy and limited specificity. Strategies to address the unmet medical need for MASH with fibrosis before it reaches the irreversible stage of decompensated cirrhosis are critically needed.

Optimized inhaled LNP formulation for enhanced treatment of idiopathic pulmonary fibrosis via mRNA-mediated antibody therapy.

Lipid nanoparticle-assisted mRNA inhalation therapy necessitates addressing challenges such as resistance to shear force damage, mucus penetration, cellular internalization, rapid lysosomal escape, and target protein expression. Here, we introduce the innovative "LOOP" platform with a four-step workflow to develop inhaled lipid nanoparticles specifically for pulmonary mRNA delivery. iLNP-HP08 featuring a high helper lipid ratio, acidic dialysis buffer, and excipient-assisted nebulization buffer, demonstrates exceptional stability and enhanced mRNA expression in the lungs.

Injectable Gelled Multiple Emulsion for Glucose-Responsive Insulin Delivery.

A glucose-responsive insulin delivery system that sustains blood glucose equilibrium for an extended duration can address the low therapeutic window of insulin in diabetes treatment. Herein, insulin is loaded in a water-in-oil-in-water (W/O/W) gelled multiple emulsion using poly (4-vinylphenylboronic acid) (PVPBA) homopolymer as an effective emulsifier. The gelled multiple emulsion exhibits a high encapsulation efficiency (99%), enhanced stability and remarkable shear-thinning behavior, making it easy to inject.

Delivery of mRNA Encoding Interleukin-12 and a Stimulator of Interferon Genes Agonist Potentiates Antitumor Efficacy through Reversing T Cell Exhaustion.

T cell exhaustion has emerged as a major hurdle that impedes the clinical translation of stimulator of interferon genes (STING) agonists. It is crucial to explore innovative strategies to rejuvenate exhausted T cells and potentiate the antitumor efficacy. Here, we propose an approach utilizing MSA-2 as a STING agonist, along with nanoparticle-mediated delivery of mRNA encoding interleukin-12 (IL-12) to restore the function of T cells.

Modulating Plaque Inflammation Targeted mRNA Nanoparticles for the Treatment of Atherosclerosis.

Atherosclerosis is a common pathology present in many cardiovascular diseases. Although the current therapies (including statins and inhibitors of the serine protease PCSK9) can effectively reduce low-density lipoprotein (LDL) cholesterol levels to guideline-recommended levels, major adverse cardiovascular events still occur frequently. Indeed, the subendothelial retention of lipoproteins in the artery wall triggers multiple events of inflammation in macrophages and is a major contributor to the pathological progression of atherosclerosis.

Nanoparticle-Mediated RNA Therapy Attenuates Nonalcoholic Steatohepatitis and Related Fibrosis by Targeting Activated Hepatic Stellate Cells.

Chronic liver injury and inflammation triggered by metabolic abnormalities initiate the activation of hepatic stellate cells (HSCs), driving fibrosis and parenchymal dysfunction, culminating in disorders such as nonalcoholic steatohepatitis (NASH). Unfortunately, there are currently no approved drugs capable of effectively treating NASH due to the challenges in addressing fibrosis and restoring extracellular matrix (ECM) homeostasis. We discovered a significant up-regulation of interleukin-11 (IL-11) in fibrotic livers using two well-established murine models of NASH.

Effects of a Proteoglycan on Type 2 Diabetic Rats and the Recovery of Rat Pancreatic Islets.

Type 2 diabetes (T2D) results from both insulin resistance and pancreatic β-cell dysfunction. A natural proteoglycan extracted from , namely, , has been demonstrated to be capable of ameliorating insulin resistance in previous work. In this work, a T2D rat model induced by streptozocin (STZ) and a high-fat diet was used to investigate the effects of on pancreatic functions, and the transcriptomics of the rat pancreas was used to investigate the biological processes (BP) and signal pathways influenced by on the gene basis.

Rational design of engineered H-ferritin nanoparticles with improved siRNA delivery efficacy across an model of the mouse BBB.

Gene therapy holds tremendous potential for the treatment of incurable brain diseases including Alzheimer's disease (AD), stroke, glioma, and Parkinson's disease. The main challenge is the lack of effective gene delivery systems traversing the blood-brain barrier (BBB), due to the complex microvessels present in the brain which restrict substances from the circulating blood passing through. Recently, increasing efforts have been made to develop promising gene carriers for brain-related disease therapies.

Antioxidation of a proteoglycan from Ganoderma lucidum protects pancreatic β-cells against oxidative stress-induced apoptosis in vitro and in vivo.

Oxidative stress is one of the major factors in induction of pancreatic β-cell apoptosis and diabetes. Here, we investigated systematically the roles of a proteoglycan (namely, FYGL) from Ganoderma lucidum in protection and repair of pancreatic β-cells against oxidative stress-induced injury and apoptosis on molecular, cellular and animal basis. FYGL in vitro had antioxidant activity in terms of scavenging of free radicals and reduction power.

Interaction and Inhibition of a Proteoglycan on PTP1B Activity for Anti-diabetes.

Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin and an effective target for the treatment of type 2 diabetes (T2D). A natural hyperbranched proteoglycan extracted from , namely, Fudan-Yueyang (), was demonstrated capable of inhibiting the activity of PTP1B. Here, to identify the effective active components of , three different components, the polysaccharide , proteoglycans , and , were isolated from , and then, the protein moiety of was further separated, namely, .

The thermodynamic and kinetic mechanisms of a Ganoderma lucidum proteoglycan inhibiting hIAPP amyloidosis.

Ganoderma lucidum is a valuable medicinal herbal which has been reported to prevent type 2 diabetes (T2D). A natural hyperbranched proteoglycan extracted from Ganoderma lucidum, namely, FYGL, has been demonstrated to inhibit the amyloidosis of human islet amyloid polypeptide (hIAPP) previously by our lab. However, the effective active components and the mechanisms of FYGL in inhibiting hIAPP amyloidosis are unknown.

Pancreatic cancer cell apoptosis is induced by a proteoglycan extracted from .

The Traditional Chinese Medicine, , has been widely used for its immunity-related and anti-cancer effects. Fudan-Yueyang-Ganoderma lucidum (FYGL) is a proteoglycan, extracted from , that has shown safe anti-diabetic activity . The present study demonstrated that FYGL could selectively inhibit the viability of PANC-1 and BxPC-3 pancreatic cancer cells in a dose dependent manner, but not in Mia PaCa-2 pancreatic cancer cells and HepG2 liver cancer cells.

A proteoglycan extract from protects pancreatic beta-cells against STZ-induced apoptosis.

The pancreatic β-cell death or dysfunction induced by oxidative stress plays an important effect on the development and progression of diabetes mellitus. Based on our previous findings, a natural proteoglycan extracted from , named , could treat T2DM . In this study, we investigated the effects of on STZ-induced apoptosis of INS-1 cells and its underlying mechanisms.

Amelioration of the Lipogenesis, Oxidative Stress and Apoptosis of Hepatocytes by a Novel Proteoglycan from Ganoderma lucidum.

The steatosis and resultant oxidative stress and apoptosis play the important roles in the progression of nonalcoholic fatty liver disease (NAFLD), therefore, searching for the effective drugs against NAFLD has been a hot topic. In this work, we investigated a hyperbranched proteoglycan, namely FYGL extracted from Ganoderma lucidum, inhibiting the palmitic acid (PA)-induced steatosis in HepG2 hepatocytes. FYGL compose of hydrophilic polysaccharide and lipophilic protein.

NIR-controlled HSP90 inhibitor release from hollow mesoporous nanocarbon for synergistic tumor photothermal therapy guided by photoacoustic imaging.

Photothermal therapy (PTT) has been widely studied for tumor therapy. However, the clinical transformation of PTT has encountered significant challenges in tumor recurrence, because the uneven hyperthermia in tumor tissues can result in the survival of cancer cells in the lower temperature regions close to blood vessels (as the blood flow can dissipate the localized heat). It is therefore important for clinical treatments to retain the excellent therapeutic efficiency of PTT at relatively low temperatures.

Complex of EGCG with Cu(II) Suppresses Amyloid Aggregation and Cu(II)-Induced Cytotoxicity of α-Synuclein.

Accumulation of α-synuclein (α-Syn) is a remarkable pathology for Parkinson's disease (PD), therefore clearing it is possibly a promising strategy for treating PD. Aberrant copper (Cu(II)) homeostasis and oxidative stress play critical roles in the abnormal aggregation of α-Syn in the progress of PD. It is reported that the polyphenol (-)-epi-gallocatechin gallate (EGCG) can inhibit α-Syn fibrillation and aggregation, disaggregate α-Syn mature fibrils, as well as protect α-Syn overexpressed-PC12 cells against damage.