Mechanism of melanogenesis inhibition by Keggin-type polyoxometalates.

Abnormal melanin overproduction can result in hyperpigmentation syndrome in human skin diseases and enzymatic browning of fruits and vegetables. Recently, our group found that Keggin-type polyoxometalates (POMs) can efficiently inhibit tyrosinase activity. However, it remains unclear whether Keggin-type POMs exhibit optimal effects in vivo. Additionally, the inhibitory effect and mechanism of action of POMs on cellular tyrosinase activity and melanogenesis have been rarely reported. Here we demonstrate that our screened and synthesised PMo11Zn and GaMo12 show superior inhibitory effects on melanin formation as well as inhibition of cellular tyrosinase activity compared to other Keggin-type POMs. Intriguingly, we reveal that Keggin-type POMs competitively bind to tyrosinase mainly through more interactions with Cu2+ ions and the amino acid residue is capable of forming van der Waals, cation-π and hydrogen bonds, resulting in a reversible non-covalent complex formation. Our findings provide valuable insights into the design, synthesis and screening of polyoxometalates as multifunctional metallodrugs and food preservatives against hyperpigmentation.

A study of the antioxidant properties of Keggin-type polyoxometalates.

In this paper, we used extracellular reactive oxygen radical scavenging assay and cellular antioxidant assay to investigate the antioxidant ability of Keggin-type polyoxometalates on the inside and outside of cells influenced by three different factors: heteroatom substitution, transition metal substitution and the number of vanadium substitutions. The results showed that the IC50 values of heteroatomic (P, Si, Ga) polyoxometalates on superoxide anion radical scavenging were 1.32 ± 0.00047 mg mL-1, 17.49 ± 2.47500 mg mL-1, and 66.99 ± 20.0227 mg mL-1, respectively. In comparison, PMo12 had the best ability to scavenge free radicals, and the SOD activity of PMo12 at 12.5 µmol L-1 increased by 50% compared with that of the unspiked drug, which played an antioxidant role; the scavenging effect of superoxide anion radicals of PMo11Mn in transition metals (Fe, Mn, Cu) instead of polyoxometalate (IC50 value 1.18 ± 0.0008 mg mL-1) was lower than that of unsubstituted PMo12 (IC50 value 1.32 ± 0.00047 mg mL-1), where PMo11Mn was nearly 1.5 times higher than PMo11Cu administration to reduce the number of cells by half; the PMo11V, PMo10V2, PMo9V3, PMo8V4, PMo7V5 hydroxyl radical scavenging rates (IC50 values) were 0.19 ± 0.0011 mg mL-1, 0.22 ± 0.0027 mg mL-1, 0.03 ± 0.0014 mg mL-1, 0.04 ± 0.0008 mg mL-1, and 0.11 ± 0.0005 mg mL-1, respectively, and in comparison, scavenging of PMo9V3 radicals was more effective and they acted as an antioxidant. Therefore, they can be used as good antioxidants in biological and pharmaceutical applications and play an important role in the treatment of tumours, cancer, Alzheimer's disease and other diseases.

Effect of MIPO combined with locking compression plate fixation on shoulder and elbow joint function and bone metabolic activity in adult patients with middle humeral shaft fracture.

OBJECTIVE: To analyze the effect of minimally invasive percutaneous osteosynthesis (MIPO) combined with locking compression plate fixation on middle humeral shaft fracture in adults. METHODS: The clinical data of 88 adult patients with middle humeral shaft fracture treated in Xiang'an Hospital from August 2019 to August 2021 were retrospectively analyzed. According to different surgical methods, they were assigned into an anterograde group (treated with anterograde interlocking intramedullary nail fixation, N=42) and a joint group (treated with MIPO technique combined with locking compression plate fixation, N=46 cases). The perioperative indexes and complications were compared between the two groups. The changes of Constant-Murley shoulder joint function score, Mayo elbow joint function score, bone metabolic activity indexes [collagen hydroxyl terminal peptide (CTX), type I procollagen amino acid terminal peptide (PICP), osteoprotegerin (OPG), and osteocalcin (BGP)], and bone quality indexes [bone trabecular spacing (Tb.Sp), bone volume fraction (BV/TV), bone elastic stress (ES), bone trabecula number (Tb.N), and volume organic matter content (VOC)] were observed before and after the operation for 3 months. RESULTS: The fracture healing time and postoperative hospitalization time in the joint group were shorter than those in the anterograde group. The intraoperative blood loss was less than that in the anterograde group (P<0.05). Three months after the operation, the scores of the Constant-Murley and Mayo, Tb.N, VOC, and ES in the joint group were higher than those in the anterograde group. The Tb.Sp and BV/TV were lower than those in the anterograde group (P<0.05). The serum CTX level in the joint group was lower than that in the anterograde group. The levels of PICP, OPG, and BGP were higher than those in the anterograde group (P<0.05). There was no significant difference in the total incidence of complications between the joint group and the anterograde group (P>0.05). CONCLUSION: MIPO technique combined with locking compression plate fixation can promote the healing of middle humeral shaft fracture in adults, improve the function of the shoulder joint and the elbow joint, regulate the activity of bone metabolism, and improve bone quality, without significant increase in complications.

Polyoxometalates: Study of inhibitory kinetics and mechanism against α-glucosidase.

Alpha-glucosidase is considered to be an important target for the treatment of noninsulin-dependent diabetes. In this work, the inhibitory effects of polyoxometalates (POMs) affected by three different factors (heteroatom, transition metal substitution element and vanadium substitution number) on α-glucosidase were studied. We found that POMs with Keggin-type and vanadium-substituted Dawson-type structures act as effective and mostly competitive inhibitors for α-glucosidase (IC50 values around 40-160 µM), and most compounds can compete with the substrate for the active site of α-glucosidase. By analyzing and comparing the inhibitory effects of each series of POMs on α-glucosidase, the results demonstrated that the structure and composition of the POMs themselves may indirect influence on their inhibitory capabilities. Moreover, we gained initial information about the structure-inhibition relationship of different POMs. More intriguingly, molecular docking simulation suggested that all compounds bind into the active site of α-glucosidase by multiple van-der-Waals and hydrogen bond interactions. Our kinetic data demonstrate the considerable potential of POMs for the development of clinically valuable α-glucosidase inhibitors.

Inhibitory effects of α-Na8SiW11CoO40 on tyrosinase and its application in controlling browning of fresh-cut apples.

α-Na8SiW11CoO40 was synthesized and characterized. The inhibitory effects of α-Na8SiW11CoO40 on the activity of mushroom tyrosinase and the effects of α-Na8SiW11CoO40 on the browning of fresh-cut apples were studied. The Native-PAGE result showed that α-Na8SiW11CoO40 had a significant inhibitory effect on tyrosinase. Kinetic analyses showed that α-Na8SiW11CoO40 was an irreversible and competitive inhibitor. The inhibitor concentration leading to a 50% reduction in activity (IC50) was estimated to be 0.239 mM. Additionally, the results also showed that α-Na8SiW11CoO40 treatment could significantly decrease the browning process of apple slices and inhibit the polyphenol oxidase (PPO) activity. Moreover, application of α-Na8SiW11CoO40 resulted in higher peroxidase activity and promoted high amounts of phenolic compounds and ascorbic acid. This study may provide a promising method for the use of polyoxometalates to inhibit tyrosinase activity and control the browning of fresh-cut apples.