3,4,3′-Tri-O-methylellagic acid as an anticancer agent: in vitro and in silico studies

We report a natural product compound isolated from Syzygium polycephalum known as 3,4,3′-tri-O-methylellagic acid (T-EA) as a candidate drug for cancer treatment. The characterization of the isolated T-EA compound was carried out using various spectroscopic methods. The in vitro evaluation showcased the inhibition activity of T-EA towards the T47D and HeLa cell lines with EC₅₀ values of 55.35 ± 6.28 μg mL⁻¹ and 12.57 ± 2.22 μg mL⁻¹, respectively. Meanwhile, the in silico evaluation aimed to understand the interaction of T-EA with enzymes responsible for cancer regulation at the molecular level by targeting the hindrance of cyclin-dependent kinase 9 (CDK9) and sirtuin 1 (SIRT1) enzymes. T-EA showed a binding free energy towards the SIRT1 protein of ΔG_{bind (MM-GBSA)}: −30.98 ± 0.25 kcal mol⁻¹ and ΔG_{bind (MM-PBSA)}: −24.07 ± 0.30 kcal mol⁻¹, while that of CDK9 was ΔG_{bind (MM-GBSA)}: −29.50 ± 0.22 kcal mol⁻¹ and ΔG_{bind (MM-PBSA)}: −25.87 ± 0.40 kcal mol⁻¹. The obtained results from this research could be considered as important information on 3,4,3′-tri-O-methylellagic acid as a drug to treat cervical and breast cancers.

We report a natural product compound isolated from Syzygium polycephalum known as 3,4,3′-tri-O-methylellagic acid (T-EA) as a candidate drug for cancer treatment using in vitro and in silico approaches.     

回春液补肾助阳药效学的实验研究

回春液由人参、鹿茸、貂鞭等名贵中药组成。有补肾助阳,填精益气等功效。药效学研究证实,该药有促进幼鼠发育及增加去势大鼠前列腺——精液囊的重量,亦显著增加小鼠血红蛋白的含量,表明回春液有雄性激素样作用。     

Salvage Hip Arthroplasty After Failed Fixation of Proximal Femur Fractures

We reviewed 46 patients who underwent salvage hip arthroplasty (SHA) for revision of failed cannulated screws (CS), sliding hip screws (SHS), or intramedullary nails (IMN). The primary objective was to determine differences in operative difficulty. SHA after failed femoral neck fixation was associated with lower intra-operative demands than after failed peri-trochanteric fractures. Similarly, analysis by the index implant found that conversion arthroplasty after failed CSs was associated with lower intra-operative morbidity than failed SHSs or IMNs; differences between SHS and IMN were not as clear. Importantly, intra-operative data in cases of failed SHSs were similar regardless of the original fracture type, showing the device played a larger role than the fracture pattern. Complications and revision surgery rates were similar regardless of fracture type or fixation device. Our results suggest that operative demands and subsequent patient morbidity are more dependent on the index device than the fracture pattern during SHA.     

Subclavian stenting in a hostile aortic arch facilitated by a low-profile brachial artery through-and-through access

Subclavian stenting can be extremely difficult in a hostile type II aortic arch (with acute angulation of the subclavian artery origin) or type III aortic arch. This case illustrates use of a low-profile system to gain through-and-through (flossing) access through the brachial artery to facilitate stenting via the femoral approach. This approach can be useful in patients with small brachial arteries where the risk of complication may be high if a standard vascular sheath was placed for stenting via the brachial approach. This technique also avoids the use of a surgical cut down.     

Mangiferin Stimulates Carbohydrate Oxidation and Protects Against Metabolic Disorders Induced by High-Fat Diets

Excessive dietary fat intake causes systemic metabolic toxicity, manifested in weight gain, hyperglycemia, and insulin resistance. In addition, carbohydrate utilization as a fuel is substantially inhibited. Correction or reversal of these effects during high-fat diet (HFD) intake is of exceptional interest in light of widespread occurrence of diet-associated metabolic disorders in global human populations. Here we report that mangiferin (MGF), a natural compound (the predominant constituent of Mangifera indica extract from the plant that produces mango), protected against HFD-induced weight gain, increased aerobic mitochondrial capacity and thermogenesis, and improved glucose and insulin profiles. To obtain mechanistic insight into the basis for these effects, we determined that mice exposed to an HFD combined with MGF exhibited a substantial shift in respiratory quotient from fatty acid toward carbohydrate utilization. MGF treatment significantly increased glucose oxidation in muscle of HFD-fed mice without changing fatty acid oxidation. These results indicate that MGF redirects fuel utilization toward carbohydrates. In cultured C2C12 myotubes, MGF increased glucose and pyruvate oxidation and ATP production without affecting fatty acid oxidation, confirming in vivo and ex vivo effects. Furthermore, MGF inhibited anaerobic metabolism of pyruvate to lactate but enhanced pyruvate oxidation. A key target of MGF appears to be pyruvate dehydrogenase, determined to be activated by MGF in a variety of assays. These findings underscore the therapeutic potential of activation of carbohydrate utilization in correction of metabolic syndrome and highlight the potential of MGF to serve as a model compound that can elicit fuel-switching effects.