Background: Diabetes mellitus (DM) is a common metabolic disorder characterized by a persistent increment of blood glucose. Type 2 DM is characterized by insulin resistance and β-cell dysfunction. Thioredoxin-interacting protein (TXNIP) is among the factors that control the production and loss of pancreatic β-cells. Objective: Recent studies have shown that high glucose can significantly up-regulate the expression of the TXNIP. Overexpression of TXNIP in β-cells not only induced apoptosis but also decreased the production of insulin. At the same time, TXNIP deficiency protected the apoptosis of β-cells, leading to increased insulin production. Therefore, finding small molecules that can modulate TXNIP expression and downstream signalling pathways is essential. Thus, the inhibition of TXNIP has beneficial effects on the cardiovascular system and other tissues such as the heart and the kidney in DM. Therefore, DM treatment must target small TXNIP activity, inhibit expression, and promote endogenous cell mass and insulin production. Conclusion: This review briefly describes the effect mechanism, regulatory mechanism, and crystal structure of TXNIP. In addition, we highlight how TXNIP signalling networks contribute to diabetes and interact with drugs that inhibit the development often and its complexes. Finally, the current status and prospects of TXNIP targeted therapy are also discussed.
Background: Gout, an inflammatory arthritis, caused by the deposition of monosodium urate crystals into affected joints and other tissues has become one of the major health problems of today's world. The main risk factor for gout is hyperuricemia, which may be caused by excessive or insufficient excretion of uric acid. The incidence is usually in the age group of 30- 50 years, commonly in males. In developed countries, the incidence of gout ranges from 1 to 4%. Despite effective treatments, there has been an increase in the number of cases over the past few decades. Objective: In recent years, the development of targeted drugs in gout has made significant achievements. The global impact of gout continues to increase, and as a result, the focus of disease-modifying therapies remains elusive. In addition, the characterization of available instrumental compounds is urgently needed to explore the use of novel selective and key protein-ligand interactions for the effective treatment of gout. Xanthine oxidase (XO) is a key target in gout to consider the use of XO inhibitors in patients with mild to moderate condition, however, the costs are high and no other direct progress has been made. Despite many XO inhibitors, a selective potent inhibitor for XO is limited. Likewise, in recent years, attention has been focused on different strategies for the discovery and development of new selectivity ligands against transforming growth factor beta-activated kinase 1 (TAK1), a potential therapeutic target for gout. Therefore the insight on human XO structure and TAK1 provides a clue into protein-ligand interactions and provides the basis for molecular modeling and structure-based drug design. Conclusion: In this review, we briefly introduce the clinical characteristics, the development of crystal, inhibitors, and crystal structure of XO and TAK1 protein.
Background: Alzheimer's disease (AD) is an unexplained progressive degenerative brain disease; it accounts for 60-70% of dementia cases worldwide, has an estimated global incidence of 24.3 million, and is associated with deterioration of the central nervous system. Acetylcholinesterase (AChE) is an enzyme that catalyzes the breakdown of acetylcholine to acetate and choline. It is also the potential target of most of the clinically used drugs for the treatment of AD. The degeneration of cholinergic neurons and the loss of neural transmission are the main reasons for the decline of cognitive ability in AD patients. Objective: In recent years, the development of targeted drugs in AD has made significant achievements. The global impact of AD continues to grow, and as a result, the focus of disease-modifying therapies remains elusive. The role of treatment is not limited to pharmacology but involves many factors, such as the psychological, social, and economic aspects of the patient and family. AChE is an important target in AD to consider the use of AChE inhibitors in patients with mild to moderate AD, even though the costs are high and no other direct progress has been made. Although there are many AChE inhibitors, there is no selective potent inhibitor for AChE. There is still a need to address human AChE structure, provide key insights into key protein-ligand interactions, and provide the basis for molecular modeling and structure-based drug design. Conclusion: In this review, we briefly introduce the clinical characteristics of AD, the development of crystal structure, and the latest research on AD. In recent years, the development of different strategies for amyloid-β, BACE1, and type-1 interferon receptor alpha-1 has attracted great attention. There is an urgent need to further characterize available instrumental compounds to explore the use of new selectivity and key protein-ligand interactions in AD. In the past few decades, great progress has been made in the treatment of AD, but AD is still one of the world's problems, and the inability to cure AD, indicates that there is an urgent need for new treatments.
Background: The spread of new coronavirus 2019, the causative agent of viral pneumonia documented in Wuhan, brought a recent public health crisis globally. The best solution to overcome this pandemic is developing suitable and effective vaccines and therapeutics. However, discovering and creating a new drug is a lengthy process requiring rigorous testing and validation. Objective: Despite many newly discovered and old repurposed COVID-19 drugs under clinical trial, more emphasis should be given to research on COVID-19 NPs-based medicines, which could improve the efficacy of antiviral drugs to reduce their side effects. The use of NPs as carriers can reduce the frequency and duration of drug ingestion, enhance approved antiviral therapeutics' effectiveness, and overcome their limitations, such as low bioavailability. Besides, they can play a crucial role in fighting against the COVID-19 pandemic. In this regard, nanotechnology provides new opportunities to develop new strategies for preventing, diagnosing, and treating COVID-19. Conclusion: This review highlighted the importance of NMs-based technical solutions in antiviral drugs for testing against the SARS-CoV-2 virus emergencies in the form of nanotherapeutics.
Alzheimer's disease is a neurological disorder in which the death of brain cells causes memory loss and cognitive decline. The role of treatment is not limited to pharmacology, but also involves many factors, such as the psychological, social, and economic aspects of the patient and family. It is important to consider the use of AChe inhibitors in patients with mild to moderate AD, despite cost issues and in the absence of any other immediate progression. Although there are allots of currently available inhibitor for acetyl cholinesterase but there is no selective potent inhibitor for AD. so, there is an urgent need discover of compounds that are active against Acetyl cholinesterase, along with there is need of molecular modeling for identifying functional groups that may be important for inhibiting Acetyl cholinesterase activity.
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