Fenton/Fenton-like metal-based nanomaterials combine with oxidase for synergistic tumor therapy

Chemodynamic therapy (CDT) catalyzed by transition metal and starvation therapy catalyzed by intracellular metabolite oxidases are both classic tumor treatments based on nanocatalysts. CDT monotherapy has limitations including low catalytic efficiency of metal ions and insufficient endogenous hydrogen peroxide (H2O2). Also, single starvation therapy shows limited ability on resisting tumors. The “metal-oxidase” cascade catalytic system is to introduce intracellular metabolite oxidases into the metal-based nanoplatform, which perfectly solves the shortcomings of the above-mentioned monotherapiesIn this system, oxidases can not only consume tumor nutrients to produce a “starvation effect”, but also provide CDT with sufficient H2O2 and a suitable acidic environment, which further promote synergy between CDT and starvation therapy, leading to enhanced antitumor effects. More importantly, the “metal-oxidase” system can be combined with other antitumor therapies (such as photothermal therapy, hypoxia-activated drug therapy, chemotherapy, and immunotherapy) to maximize their antitumor effects. In addition, both metal-based nanoparticles and oxidases can activate tumor immunity through multiple pathways, so the combination of the “metal-oxidase” system with immunotherapy has a powerful synergistic effect. This article firstly introduced the metals which induce CDT and the oxidases which induce starvation therapy and then described the “metal-oxidase” cascade catalytic system in detail. Moreover, we highlight the application of the “metal-oxidase” system in combination with numerous antitumor therapies, especially in combination with immunotherapy, expecting to provide new ideas for tumor treatment.

Connate Myxedema- An Inadequate Thyroid Hormone Production in Newborn Infants

Connate myxedema is also known as congenital hypothyroidism is an inborn endocrine disorder, affects 1 in every 3000 to 4000 infants. Numerous genetic defects are related with perpetual congenital hypothyroidism (CH). Ambient atmosphere, iatrogenic and immunologic factors are known to cause transient congenital hypothyroidism, which resolves within first few months of life. Molecular defects of thyroid oxidase system which is composed of at least two proteins may be involved in pathogenesis of lasting transient congenital hypothyroidism in infants with faults in iodide organification, for which the oxidase system is needed. Congenital hypothyroidism is predominantly sporadic but up to 2% of thyroid dysgenesis is inherited and congenital hypothyroidism due to organification faults is often recessively inherited. Levothyroxine is the drug of choice. An infant of 10 months old was presented with hoarseness while crying and noisy breathing. I had reported a case in which patient was diagnosed with congenital hypothyroidism and is being treated with levothyroxine.

Evaluation of influence several drugs with local antimicrobial activity against local immunity cells

Currently in clinical practice widely used drugs local antimicrobial drugs such as Tantum Verde (benzydamine) Tantum Rosa (benzydamine) Miramistin (benzyldimethyl-miristoilamino-propylammonium) Hexoral (hexetidin), chlorhexidine (chlorhexidine), Septolete total (benzydamine + cetylpyridinium chloride). The mechanism of action of these very similar. We evaluated the effect of these drugs on the viability of lymphoid tissue cells and their effect on the neutrophilic part of the immune system, which are the most important factors of local immunity and, at the same time, part of the immune system which is responsible for innate immunity. We used peripheral blood from 6 healthy donors and 6 patients with inflammatory diseases (abscess of the abdominal cavity). Evaluation of the viability of lymphocytes was performed in a test using trypan blue. The functional state of neutrophils was performed in a nitro-blue tetrazolium test. The final concentration of the studied drugs in all experiments was 10% of the initial recommended for local use. The results of the study showed that Miramistin, Hexoral, Chlorhexidine, Septolete Total cause the death of lymphocytes isolated from healthy donors and patients with severe inflammation process. Tantum Verde and Tantum Rose do not cause the death of lymphocytes. All studied drugs (except Tantum Verde and Tantum Rose in healthy donors) reduce the number of neutrophils containing formazan granules, which indicates the suppression of the activity of the NADPH oxidase system. Patients’ neutrophils witch were activated by inflammatory process under the influence of miramistin experiencing short-term excessive activation of the NADPH-oxidase system, which can lead to tissue damage in severe inflammation.

Current Mechanistic Concepts in Ischemia and Reperfusion Injury

Ischemia-reperfusion injury is associated with serious clinical manifestations, including myocardial hibernation, acute heart failure, cerebral dysfunction, gastrointestinal dysfunction, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. Ischemia-reperfusion injury is a critical medical condition that poses an important therapeutic challenge for physicians. In this review article, we present recent advances focusing on the basic pathophysiology of ischemia-reperfusion injury, especially the involvement of reactive oxygen species and cell death pathways. The involvement of the NADPH oxidase system, nitric oxide synthase system, and xanthine oxidase system are also described. When the blood supply is re-established after prolonged ischemia, local inflammation and ROS production increase, leading to secondary injury. Cell damage induced by prolonged ischemia-reperfusion injury may lead to apoptosis, autophagy, necrosis, and necroptosis. We highlight the latest mechanistic insights into reperfusion-injury-induced cell death via these different processes. The interlinked signaling pathways of cell death could offer new targets for therapeutic approaches. Treatment approaches for ischemia-reperfusion injury are also reviewed. We believe that understanding the pathophysiology ischemia-reperfusion injury will enable the development of novel treatment interventions.