The serum and glucocorticoid inducible protein kinase (SGK) family members share similar structure, substrate specificity and function with AKT and signal downstream of the phosphatidylinositol 3-kinase (PI3K) signalling pathway. They regulate a range of fundamental cellular processes such as cell proliferation and survival, thereby playing an important role in cancer development. This perspective intends to give an overview on the involvement of SGKs (particularly SGK3) in cancer progression, and compares the actions of SGK3 and AKT in cell cycle regulation, oncogenic signalling, and the potential as a therapeutic target for cancer.

Telemedicine is starting to play an important role in the health field in India. In this case report we describe the successful use of telementoring to remove a parathyroid tumor in a patient with residual hyperparathyroidism after two previous unsuccessful attempts in tumor excision. A 21-yr-old patient crippled with advanced hyperparathyroidism was taken up for third-time exploration at Amrita Institute of Medical Sciences (AIMS), Kochi, with guidance from the Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, using telemedicine technology. These two centers are located 2,500 km apart, and telementoring from the more experienced endocrine surgeons at SGPGIMS resulted in successful tumor localization and removal. For this session both the institutions were provided with a dedicated 512 Kbps very small aperture terminal (VSAT) link and two-way video-audio connectivity. Even though two previous explorations were unsuccessful, with the help of telemedicine technology the same surgeon was successful in locating and removing the tumor. The video and audio quality was of good enough quality for the expert at SGPGIMS to guide the team at AIMS satisfactorily. The patient benefited since he did not have to travel to a far-off specialized center for surgery. This case report testifies to the usefulness of telemedicine in the field of surgery, especially in developing countries, which have few medical experts in certain specialized areas.

The serum and glucocorticoid-regulated kinase (SGK) family has been implicated in the regulation of many cellular processes downstream of the PI3K pathway. It plays a crucial role in PI3K-mediated tumorigenesis, making it a potential therapeutic target for cancer. SGK family consists of three isoforms (SGK1, SGK2, and SGK3), which have high sequence homology in the kinase domain and similar substrate specificity with the AKT family. In order to identify novel compounds capable of inhibiting SGK3 activity, a high-throughput screening campaign against 50,400 small molecules was conducted using a fluorescence-based kinase assay that has a Z' factor above 0.5. It identified 15 hits (including nitrogen-containing aromatic, flavone, hydrazone, and naphthalene derivatives) with IC values in the low micromolar to sub-micromolar range. Four compounds with a similar scaffold (i.e., a hydrazone core) were selected for structural modification and 18 derivatives were synthesized. Molecular modeling was then used to investigate the structure-activity relationship (SAR) and potential protein-ligand interactions. As a result, a series of SGK inhibitors that are active against both SGK1 and SGK3 were developed and important functional groups that control their inhibitory activity identified.

Dietary nutrients have significant effects on the risk of cardiovascular diseases. However, the results were not uniform across different countries. The study aims to determine the relative importance of dietary nutrients associated with coronary artery disease (CAD) among the Nepalese population. A hospital-based matched case-control study was carried out at Shahid Gangalal National Heart Center in Nepal. In the present study, patients with more than seventy percent stenosis in any main coronary artery branch in angiography were defined as cases, while those presenting normal coronary angiography or negative for stressed exercise test were considered controls. Dietary intakes of 612 respondents over the past 12 months were evaluated using a semi-quantitative customized food frequency questionnaire. In conditional regression model, the daily average dietary intake of β-carotene (OR: 0.54; 95%CI: 0.34, 0.87), and vitamin C (OR: 0.96; 95%CI: 0.93, 0.99) were inversely, whereas dietary carbohydrate (OR: 1.16; 95%CI: 1.1, 1.24), total fat/oil (OR: 1.47; 95%CI: 1.27, 1.69), saturated fatty acid (SFA) (OR: 1.2; 95%CI: 1.11, 1.3), cholesterol (OR: 1.01; 95%CI: 1.001, 1.014), and iron intakes (OR: 1.11; 95%CI: 1.03, 1.19) were positively linked with CAD. Moreover, in random forest analysis, the daily average dietary intakes of SFA, vitamin A, total fat/oil, β-carotene, and cholesterol were among the top five nutrients (out of 12 nutrients variables) of relative importance associated with CAD. The nutrients of relative importance imply a reasonable preventive measure in public health nutrients specific intervention to prevent CAD in a resource-poor country like Nepal. The findings are at best suggestive of a possible relationship between these nutrients and the development of CAD, but prospective cohort studies and randomized control trials will need to be performed in the Nepalese population.

Gut microbiota composition has caused perplexity in developing precision therapy to cure metabolic disorders. However, recent research has focused on using daily diet and natural bioactive compounds to correct gut microbiota dysbiosis and regulate host metabolism. Complex interactions between the gut microbiota and dietary compounds disrupt or integrate the gut barrier and lipid metabolism. In this review, we investigate the role of diet and bioactive natural compounds in gut microbiota dysbiosis and also the modulation of lipid metabolism by their metabolites. Recent studies have revealed that diet, natural compounds and phytochemicals impact significantly on lipid metabolism in animals and humans. These findings suggest that dietary components or natural bioactive compounds have a significant impact on microbial dysbiosis linked to metabolic diseases. The interaction between dietary components or natural bioactive compounds and gut microbiota metabolites can regulate lipid metabolism. Additionally, natural products can shape the gut microbiota and improve barrier integrity by interacting with gut metabolites and their precursors, even in unfavourable conditions, potentially contributing to the alignment of host physiology.

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.

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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.