Synthesis and biological evaluation of indoline derivatives as CDGSH iron sulfur domain 2 activators.

A series of indoline derivatives has been designed, synthesized, and evaluated for their capacity to activate CDGSH iron sulfur domain 2 (Cisd2), a protein implicated in nonalcoholic fatty liver disease (NAFLD), starting with 1-(2,3-dihydro-1H-indol-1-yl)-2-(4,5-dihydro-1,3-thiazol-2-ylsulfanyl)ethan-1-one 3 (EC = 569 nM), the hit identified through a two-stage screening strategy followed by substructure searches. Among them, indolines 7 (EC = 364 nM) and 10 (EC = 315 nM) stood out as the most potent Cisd2 activators and were advanced to in vivo studies. The data conclusively demonstrated that both compounds enhanced Cisd2 expression, yet only 7 effectively halted the development and progression of NAFLD without any detectable toxicity; compound 10 was linked to hepatotoxicity, highlighting its potential risks.

Lumbrokinase-containing gelatin nanofibers with multiple bioactivities for effective skin wound healing.

Wound healing is a highly complex and intricate biological process involving cellular and molecular events. Given that lumbrokinase is a fibrinolytic enzyme derived from earthworms and exhibits notable anti-inflammatory, anti-fibrotic, and pro-angiogenic functions, this study aims to investigate the development of bioactive gelatin nanofibers containing lumbrokinase (GLK) fabricated through electrospinning as a novel nanomedicine strategy for enhancing wound healing. Our results showed that reducing electrospinning time can increase cross-linking degree and decrease degradation rate to maintain an effective concentration of released LK for supporting long-term biological processes.

Comparing Clinical Outcomes of Microdiscectomy, Interspinous Device Implantation, and Full-Endoscopic Discectomy for Simple Lumbar Disc Herniation.

: The treatment for lumbar disc herniation (LDH) is surgical discectomy. This surgery may enhance spinal instability and exacerbate disc degeneration. The most common treatment options include microdiscectomy (MD), interspinous process device (IPD) implantation, and percutaneous endoscopic lumbar discectomy (PELD).

Alginate-functionalized nanoceria as ion-responsive eye drop formulation to treat corneal abrasion.

In this study, we aimed to develop ion-responsive and biocompatible alginate-capped nanoceria (Ce-ALG) for β-1,3-glucan (i.e., wound healing agent) delivery and corneal abrasion (CA) treatment.

Increased Incidence of Surgical Intervention for Otitis Media With Effusion Among Patients With Type 2 Inflammatory Diseases.

Background: Otitis media with effusion (OME) is associated with comorbidities such as allergic rhinitis, gastroesophageal reflux disease, asthma, and more. Many of these comorbidities can be caused by type 2 inflammation (T2I). This study aims to determine the risk of undergoing OME surgery in patients with and without T2I disease.

Naringin Induces ROS-Stimulated G Cell-Cycle Arrest and Apoptosis in Nasopharyngeal Carcinoma Cells.

Naringin, a bioflavonoid compound from grapefruit or citrus, exerts anticancer activities on cervical, thyroid, colon, brain, liver, lung, thyroid, and breast cancers. The present investigation addressed exploring the anticancer effects of naringin on nasopharyngeal carcinoma (NPC) cells. Naringin exhibits a cytotoxic effect on NPC-TW 039 and NPC-TW 076 cells with IC 372/328 and 394/307 μM for 24 or 48 h, respectively, while causing little toxicity toward normal gingival epithelial (SG) cells (>500/500 μM).

Incense-burning smoke ingredient Auramine enhances lincRNA-p21 expression for chemosensitization in p53-mutated non-small cell lung cancer.

Incense-burning smoke is a deleterious air pollutant that initiates cytotoxic effects by inducing apoptosis in lung epithelial cells and also acts as a risk factor for lung cancers. Auramine, an ingredient of incense smoke, has been implicated in tumor progression and cellular sensitivity in non-small cell lung cancer (NSCLC) towards anti-cancer agents through unclear mechanisms. Tumor protein p53 (TP53)-activated long intergenic non-coding RNA-p21 (lincRNA-p21) undertakes a pivotal role in regulating cell apoptosis and chemosensitivity.

Anethole mitigates H O -induced inflammation in HIG-82 synoviocytes by suppressing the aquaporin 1 expression and activating the protein kinase A pathway.

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease affecting approximately 1% of the global population, with a higher prevalence in women than in men. Chronic inflammation and oxidative stress play pivotal roles in the pathogenesis of RA. Anethole, a prominent compound derived from fennel (Foeniculum vulgare), possesses a spectrum of therapeutic properties, including anti-arthritic, anti-inflammatory, antioxidant, and tumor-suppressive effects.

Upregulation Attenuated the KRAS-PI3K-Rac1-Akt Axis-Mediated Bioenergetic Functions.

The aberrant activation of signaling pathways contributes to cancer cells with metabolic reprogramming. Thus, targeting signaling modulators is considered a potential therapeutic strategy for cancer. Subcellular fractionation, coimmunoprecipitation, biochemical analysis, and gene manipulation experiments revealed that decreasing the interaction of kirsten rat sarcoma viral oncogene homolog (KRAS) with p110α in lipid rafts with the use of naringenin (NGN), a citrus flavonoid, causes lipid raft-associated phosphatidylinositol 3-kinase (PI3K)-GTP-ras-related C3 botulinum toxin substrate 1 (Rac1)-protein kinase B (Akt)-regulated metabolic dysfunction of glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), leading to apoptosis in human nasopharyngeal carcinoma (NPC) cells.

Folic Acid and Folinic Acid Protect Hearts of Aging Triple-transgenic Alzheimer's Disease mice via IGF1R/PI3K/AKT and SIRT1/AMPK Pathways.

Patients with Alzheimer's disease have increased risk of developing heart disease, which therefore highlights the need for strategies aiming at reducing Alzheimer's disease-related cardiovascular disease. Folic acid and folinic acid are beneficial to the heart. We aimed to investigate the benefits of folic acid and folinic acid in heart of patients with late-stage Alzheimer's disease.

Feasibility evaluation of N-Isopropyl Acrylamide 3D gel dosimeters for proton therapy.

This study aimed to investigate the feasibility of applying 3D gel dosimeters for proton therapy. Two different formulations (5-5-3-5, 5-3-3-10) for the N-Isopropyl Acrylamide (NIPAM) polymer gel were used to find the best composition for the application of NIPAM polymer gels for proton therapy. The reaction of the gel under different physical conditions, including dependence on energy and dependence on the dose rate of the NIPAM gel under proton irradiation, was also explored.

Ex Vivo Model to Evaluate the Antibacterial and Anti-Inflammatory Effects of Gelatin-Tricalcium Phosphate Composite Incorporated with Emodin and Lumbrokinase for Bone Regeneration.

Tricalcium phosphate (TCP) has gained attention due to its interconnected porous structures which promote fibrovascular invasion and bony replacement. Moreover, when gelatin is added and crosslinked with genipin (GGT), TCP exhibits robust biocompatibility and stability, making it an excellent bone substitute. In this study, we incorporated emodin and lumbrokinase (LK) into GGT to develop an antibacterial biomaterial.

Ligustrazine improves the compensative effect of Akt survival signaling to protect liver Kupffer cells in trauma-hemorrhagic shock rats.

Trauma-hemorrhagic shock (THS) is a medical emergency that is encountered by physicians in the emergency department. Chuan Xiong is a traditional Chinese medicine and ligustrazine is a natural compound from it. Ligustrazine improves coronary blood flow and reduces cardiac ischemia in animals through Ca and ATP-dependent vascular relaxation.

Discovery of tetrasubstituted thiophenes as Cisd2 activators: A potential novel therapeutic option in nonalcoholic fatty liver disease.

Down-regulation of Cisd2 in the liver has been implicated in the development of nonalcoholic fatty liver disease (NAFLD) and increasing the level of Cisd2 is therefore a potential therapeutic approach to this group of diseases. Herein, we describe the design, synthesis, and biological evaluation of a series of Cisd2 activators, all thiophene analogs, based on a hit obtained using two-stage screening and prepared via either the Gewald reaction or by intramolecular aldol-type condensation of an N,S-acetal. Metabolic stability studies of the resulting potent Cisd2 activators suggest that thiophenes 4q and 6 are suitable for in vivo studies.

Design, synthesis, and anticancer evaluation of 1-benzo[1,3]dioxol-5-yl-3-N-fused heteroaryl indoles.

A series of 1-benzo[1,3]dioxol-5-yl-indoles bearing 3-N-fused heteroaryl moieties have been designed based on literature reports of the activity of indoles against various cancer cell lines, synthesized via a Pd-catalyzed C-N cross-coupling, and evaluated for their anticancer activity against prostate (LNCaP), pancreatic (MIA PaCa-2), and acute lymphoblastic leukemia (CCRF-CEM) cancer cell lines. A detailed structure-activity relationship study culminated in the identification of 3-N-benzo[1,2,5]oxadiazole 17 and 3-N-2-methylquinoline 20, whose IC values ranged from 328 to 644 nM against CCRF-CEM and MIA PaCa-2. Further mechanistic studies revealed that 20 caused cell cycle arrest at the S phase and induced apoptosis in CCRF-CEM cancer cells.

Neuroprotective Effects of Probiotic Lactobacillus reuteri GMNL-263 in the Hippocampus of Streptozotocin-Induced Diabetic Rats.

Diabetes-related brain complications have been reported in clinical patients and experimental models. The objective of the present study was to investigate the neuroprotective mechanisms of Lactobacillus reuteri GMNL-263 in streptozotocin (STZ)-induced diabetic rats. In this study, three different groups, namely control group, STZ-induced (55 mg/kg streptozotocin intraperitoneally) diabetic rats (DM), and DM rats treated with Lactobacillus reuteri GMNL-263 (1 × 10 CFU/rat/day), were utilized to study the protective effect of GMNL-263 in the hippocampus of STZ-induced diabetic rats.

Oxidation-mediated scaffold engineering of hyaluronic acid-based microcarriers enhances corneal stromal regeneration.

The functional design of scaffolding biomaterials with potent capabilities of promoting cell adhesion and proliferation is critically important for tissue repair and regeneration. Here, we exploit the effects of oxidation level of aldehyde hyaluronic acid (oHA) on gelatin microcarriers for repairing corneal injuries. Specifically, high oxidation levels can endow the microcarrier surface with large oHA grafting amount, smooth topography, and strong stiffness, consequently formulating biocompatible scaffolding materials with superior affinities for keratocyte attachment and growth.

Remodeling Effects of the Combination of GGT Scaffolds, Percutaneous Electrical Stimulation, and Acupuncture on Large Bone Defects in Rats.

The regeneration defect of bone is a long-term physiological process after bone injuries. To accelerate the bone remodeling process, the combination of chemical and physical stimulations provides an efficient strategy to allow maturation and to functionalize osteoclasts and osteoblasts. This study aims to investigate the dual effects of a tricalcium phosphate (TCP)-based gelatin scaffold (GGT) in combination with electroacupuncture stimulation on the activation of osteoclasts and osteoblasts, as well as new bone regrowth .

Snail Mucus Enhances Chemosensitivity of Triple-negative Breast Cancer Activation of the Fas Pathway.

Background/aim: The poor prognosis and chemoresistance of patients with triple-negative breast cancer (TNBC) urge the development of new therapeutic strategies. Snail mucus has shown its ability against inflammation, a process closely related to tumorigenesis, suggesting a potential anti-cancer activity.

Materials And Methods: The effect and mechanisms of snail mucus on cell viability were determined by IncuCyte Live-cell analysis and molecular biological methods.

Arecoline induces cardiotoxicity by upregulating and activating cardiac hypertrophy-related pathways in Sprague-Dawley rats.

Habitual chewing of the areca nut increases the risk of mortality owing to cardiovascular disease, but few reports have revealed the cardiotoxicity mechanism of the areca nut. Arecoline has been reported to be the primary toxic constituent in the areca nut. In order to study the acute cardiotoxicity of the areca nut in the development of pathologic heart hypertrophy, we induced heart injury in rats using arecoline.

Calycosin alleviates H O -induced astrocyte injury by restricting oxidative stress through the Akt/Nrf2/HO-1 signaling pathway.

Oxidative stress-induced brain cell damage is a crucial factor in the pathogenesis of reactive oxygen species (ROS)-associated neurological diseases. Further, studies show that astrocytes are an important immunocompetent cell in the brain and play a potentially significant role in various neurological diseases. Therefore, elimination of ROS overproduction might be a potential strategy for preventing and treating neurological diseases.

Fabrication of 3D Printed Poly(lactic acid)/Polycaprolactone Scaffolds Using TGF-β1 for Promoting Bone Regeneration.

Our research was designed to evaluate the effect on bone regeneration with 3-dimensional (3D) printed polylactic acid (PLA) and 3D printed polycaprolactone (PCL) scaffolds, determine the more effective option for enhancing bone regeneration, and offer tentative evidence for further research and clinical application. Employing the 3D printing technique, the PLA and PCL scaffolds showed similar morphologies, as confirmed via scanning electron microscopy (SEM). Mechanical strength was significantly higher in the PLA group (63.

Doxorubicin-Gelatin/FeO-Alginate Dual-Layer Magnetic Nanoparticles as Targeted Anticancer Drug Delivery Vehicles.

In this study, magnetic nanoparticles composed of a core (doxorubicin-gelatin) and a shell layer (FeO-alginate) were developed to function as targeted anticancer drug delivery vehicles. The anticancer drug doxorubicin (DOX) was selected as a model drug and embedded in the inner gelatin core to obtain high encapsulation efficiency. The advantage of the outer magnetic layer is that it targets the drug to the tumor tissue and provides controlled drug release.

Bone Morphogenetic Protein-2-Activated 3D-Printed Polylactic Acid Scaffolds to Promote Bone Regrowth and Repair.

Uneven distribution of pores, lack of connection between holes, low reproducibility, insufficient mechanical strength, and incomplete volatility of organic solvents are some problems associated with traditional tissue engineering methods for bone defect repair. These characteristics reduce the quality and stability of products. This study uses 3D printing (3DP) to fabricate a biocompatible poly(lactic) acid-based scaffold for repairing bone tissue.