Diabetes Mellitus (DM) is one of the highest contributors to global mortality, exceeding numbers of even the three major infectious diseases in the world, namely Tuberculosis, HIV AIDS, and Malaria. DM is characterised by increased serum levels of glucose caused by a loss of beta cells of the pancreatic islets, responsible for the secretion of insulin. Upon accumulation of data via a wide array of literature surveys, it has been found that Thioredoxin Interacting Protein (TXNIP) presents itself as a vital factor in controlling the production and loss of beta islet cells. TXNIP inhibits the action of the Thioredoxin (TRX) protein found in the beta cells thereby rendering it ineffective in maintaining the cellular redox balance causing oxidative stress and subsequent consequences ultimately leading to aggravation of the disease. TRX exists in the form of two isoforms - TRX1, which is located in the cytosol and at times translocates to the nucleus, and TRX2, which is located in the nucleus. TRX is responsible for the maintenance of the normal cellular redox balance by reducing the oxidised proteins formed by the Reactive Oxygen Species (ROS) with the help of NADPH dependent TRX Reductase enzyme. This proves to be essential in the pathogenesis of Diabetes Mellitus as the beta cells of the pancreatic islets lack a sufficient amount of antioxidant systems. Thus, inhibition of TXNIP has become essential in the survival of beta cells, not only enhancing insulin secretion and sensitivity but also alleviating the diseases associated with Diabetes. Hence, TXNIP is discovered to be a unique therapeutic target in the management of DM.

Introduction: Thioredoxin reductase (TrxR) is a selenocysteine-containing enzyme which is responsible - as a part of the thioredoxin system - for maintaining redox homeostasis in cells. It is upregulated in cancerous state as a defense against oxidative stress. TrxR has been mostly considered an anticancer drug target although it has applications in other therapeutic areas such as neurodegeneration, inflammation, microbial infections, and neonatal hyperoxic lung injury.Areas covered: The present review covers the patent literature that appeared in the period 2017-2020, i.e. since the publication of the previous expert opinion patent review on TrxR inhibitors. The recent additions to the following traditional classes of inhibitors are discussed: metal complexes, Michael acceptors as well as arsenic and selenium compounds. At the same time, a novel group of nitro (hetero)aromatic compounds have emerged which likely acts via covalent inhibition mechanism. Several miscellaneous chemotypes are grouped under Miscellaneous subsection.Expert opinion: While specificity over glutathione reductase is achieved easily, TrxR is still moving toward the later stages of development at a very slow rate. Michael acceptors, particularly based on TRXR substrate-mimicking scaffolds, are gaining impetus and so are dual and hybrid compounds. The development prospects of the emerging nitro (hetero)aromatic chemotypes remain uncertain.

BACKGROUND: The aim of this study is to explore the effect of grelin on TRX expression (TRXE) in chronic heart failure tissue (CHFT).
METHODS: We will search electronic databases from inception to the March 1, 2020 in MEDLINE, EMBASE, Cochrane Library, CINAHL, PEDro, the Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. We will not apply any limitations to the language and publication status. Any randomized controlled trials (RCTs) that studied the effect of grelin on TRXE in CHFT will be included. Study quality will be checked by Cochrane risk of bias and evidence quality will be appraised by Grading of Recommendations Assessment Development and Evaluation. All extracted data will be analyzed by RevMan 5.3 Software.
RESULTS: This study will summarize the present RCTs to assess the effect of grelin on TRXE in CHFT.
CONCLUSIONS: The results of this study will provide conclusive evidence of the effect of grelin on TRXE in CHFT.
BACKGROUND: INPLASY202040078.

Understanding and elucidating the mechanism of host-pathogen interactions are the major area of interest among the Parasitologists all around the globe. Starting from the origin on mother earth parasites have searched for successful strategies to invade their respective host for the sake of survivability and eventually succeeded to manage in the unfriendly environment inside the host\'s body. Parasite-generated antioxidants are potent enough to combat the oxidative challenges inside the host body and within its own as well. Antioxidant enzymes are tremendously important as they are directly related to the survival of the parasites. The thiol-based antioxidant enzymes (glutathione reductase and thioredoxin reductase) have dragged much attention of the researchers to date. In this regard, among the thiol-based antioxidants, particularly the Thioredoxin reductase (TrxR), is known to be present in a number of parasitic organisms have pulled the researchers. Therefore, selective targeting of TrxR can emerge as a novel capital for developing suitable adulticidal candidate for treating filariasis and other helminth infections. This review tries to assemble the existing knowledge of the parasitic TrxR and how these can be utilized as a druggable target in cases of filariasis and other helminth infections has been discussed.

Thioredoxin (Trx), thioredoxin reductase (TrxR), and NADPH are key members of the Trx system that is involved in redox regulation and antioxidant defense. In recent years, several researchers have provided information about the roles of the Trx system in cancer development and progression. These reports indicated that many tumor cells express high levels of Trx and TrxR, which can be responsible for drug resistance in tumorigenesis. Inhibition of the Trx system may thus contribute to cancer therapy and improving chemotherapeutic agents. There are now a number of effective natural and synthetic inhibitors with chemotherapy applications possessing antitumor activity ranging from oxidative stress induction to apoptosis. In this article, we first described the features and functions of the Trx system and then reviewed briefly its correlations with cancer. Finally, we summarized the present knowledge about the Trx/TrxR inhibitors as anticancer drugs.

The chloroplastic thioredoxins (Trxs), a family of thiol-disulphide oxidoreductases, are reduced by either ferredoxin (Fd)-dependent Trx reductase (FTR) or reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent Trx reductase (NTR). Two Trx systems are present in chloroplasts including Trxs, Trx-like proteins, and reductase FTR and NTRC. FTR is the main reductant for Trxs in chloroplasts, while the flavoprotein NTRC integrates NTR and Trx activity, and plays multiple roles in the Calvin cycle, the oxidative pentose phosphate pathway (OPPP), anti-peroxidation, tetrapyrrole metabolism, ATP and starch synthesis, and photoperiodic regulation. In addition, not only there exists a reduction potential transfer pathway across the thylakoid membrane, but also FTR and NTRC coordinate with each other to regulate chloroplast redox homeostasis. Herein, we summarise the physiological functions of these two Trx reduction systems, discuss how both regulate redox homeostasis in plant plastids, and emphasize the significance of chloroplast thioredoxin systems in maintaining photosynthetic efficiency in plants.

Antimicrobial peptides are of great interest due to their potential application as novel antibiotics. Large quantities of highly purified peptides are required to meet the needs of basic research and clinical trials. Compared with isolation from natural sources and chemical synthesis, recombinant approach offers the most cost-effective means for large-scale peptide manufacture. Among the systems available for heterologous protein production, Escherichia coli has been the most widely used host. Antimicrobial peptides produced in E. coli are often expressed as fusion proteins, a strategy necessary to mask these peptides\' lethal effect towards the host and protect them from proteolytic degradation. The present article reviews commonly used fusion partners (e.g., solubility-enhancing, aggregation-promoting and self-cleavable carriers, etc.), cleavage methods and optimization options for antimicrobial peptides production in E. coli. In addition, the various approaches developed to generate recombinant human antimicrobial peptide LL-37, which offer excellent examples demonstrating effective production strategies, were briefly discussed.

BACKGROUND: Observational epidemiological studies of dietary antioxidant intake, serum antioxidant concentration and lung outcomes suggest that lower levels of antioxidant defences are associated with decreased lung function. Another approach to understanding the role of oxidant/antioxidant imbalance in the risk of chronic obstructive pulmonary disease (COPD) is to investigate the role of genetic variation in antioxidant enzymes, and indeed family based studies suggest a heritable component to lung disease. Many studies of the genes encoding antioxidant enzymes have considered COPD or COPD related outcomes, and a systematic review is needed to summarise the evidence to date, and to provide insights for further research.
METHODS: Genetic association studies of antioxidant enzymes and COPD/COPD related traits, and comparative gene expression studies with disease or smoking as the exposure were systematically identified and reviewed. Antioxidant enzymes considered included enzymes involved in glutathione metabolism, in the thioredoxin system, superoxide dismutases (SOD) and catalase.
RESULTS: A total of 29 genetic association and 15 comparative gene expression studies met the inclusion criteria. The strongest and most consistent effects were in the genes GCL, GSTM1, GSTP1 and SOD3. This review also highlights the lack of studies for genes of interest, particularly GSR, GGT and those related to TXN. There were limited opportunities to evaluate the contribution of a gene to disease risk through synthesis of results from different study designs, as the majority of studies considered either association of sequence variants with disease or effect of disease on gene expression.
CONCLUSIONS: Network driven approaches that consider potential interaction between and among genes, smoke exposure and antioxidant intake are needed to fully characterise the role of oxidant/antioxidant balance in pathogenesis.

The importance of thioproteins, essential to the ribonucleotide reduction pathway, has been demonstrated in human primary and metastatic melanoma tissues. The thioredoxin reductase/thioredoxin and the glutathione reductase/glutathione/glutaredoxin electron transfer pathways represent alternative electron donors for ribonucleotide reductase and regulate the synthesis of deoxyribonucleotides, the substrates for DNA synthesis, in the S phase of the cell cycle. In addition to their important role in DNA synthesis and cell division, these thioproteins provide effective antioxidant defence against oxygen radicals and hydrogen peroxide. In human metastatic melanoma cells and tissues the thioredoxin reductase/thioredoxin system is located both in the cell cytosol and on plasma membranes and is under allosteric regulation by calcium. As a consequence, calcium plays an important role in determining the intracellular redox status, cell division and differentiation. Recently, the intracellular redox conditions have been shown to be important in the reaction of alkylating anti-tumour drugs such as the chloroethylnitrosoureas. In addition to previously established mechanisms, these highly reactive drugs inhibit thioredoxin reductase, glutathione reductase and ribonucleotide reductase by chloroethylation of their respective thiolate active sites. Incorporation of the 14C chloroethyl group in drug sensitive and resistant human metastatic melanoma cell lines depends on the redox status, with resistant cells being more oxic than sensitive cells. Thioredoxin reductase is 500-fold more sensitive than glutathione reductase to the newly developed nitrosourea, Fotemustine (diethyl-1-[3,2 chloroethyl]-3-nitrosoureido ethyl phosphonate). It has been shown that melanomas which respond to Fotemustine therapy contain more thioredoxin reductase whereas resistant metastases yielded the opposite result.(ABSTRACT TRUNCATED AT 250 WORDS)