Current Protein and Peptide Science - Current Issue

Diabetic nephropathy is characterized by elevated oxidative stress and chronic inflammation in the kidneys. A class of proteins called sirtuins is well-known to be important for a number of cellular functions, such as metabolism, stress tolerance, and ageing. Among them, SIRT1 is associated with the progression of diabetic nephropathy, a dangerous kidney-related consequence of diabetes mellitus. Thus, this study aims to examine the function and pathways of sirtuin that are responsible for the progression of this disease.

Publications considered from the standard databases like Pubmed-Medline, Google Scholar, and Scopus using standard keywords, “Sirtuin,” Signalling pathway”, and “Diabetic Nephropathy” well described the actual knowledge on the scientific literature indicating patient susceptibility to kidney disease that is influenced by sirtuin-1 gene variants.

The research results imply that sirtuins offer enormous promise as cutting-edge therapeutic targets for kidney disease prevention and management. Renal fibrosis, metabolic disorders, renal impairment, and a possible regulation mechanism all probably entail blocking inflammation through various signalling pathways.

A comprehensive understanding of the fundamental pathophysiological pathways targeting sirtuin is essential as a diagnostic tool. For the treatment of diabetic nephropathy, researchers are developing therapeutic techniques to target biological roles and functions of different types of sirtuin, processes, and signalling pathways.

Cathepsin D is a lysosomal enzyme that plays a critical role in the process of protein catabolism. In marine organisms, research has primarily concentrated on the identification of the enzyme. However, in crustaceans and molluscs, it is known to have digestive functions, as it is the sole enzyme responsible for protein degradation at extremely acidic pH in the hepatopancreas. In the Japanese clam (Ruditapes philippinarum), cathepsin D was purified and partially characterised from the hepatopancreas.

To evaluate changes in secondary structure, circular dichroism (CD) was employed under a range of 5-70°C and pH of 1-7.5. Following dissection, the enzyme was purified from the hepatopancreas by ultrafiltration and affinity chromatography. SDS-PAGE was used to verify the sample purity, and gel filtration was used to determine the molecular weight. CD spectra were obtained at a concentration of 0.125 mg/mL, expressed as mean ellipticity per residue.

The purified cathepsin D demonstrated a specific activity of 5,553 ± 220 U/mg and a molecular weight of 36.5 kDa. The enzyme demonstrated optimal activity within a temperature range of 45-50°C and a pH range of 3-3.5. CD analyses demonstrated alterations in the secondary structure at elevated temperatures and pH fluctuations, which were correlated with a reduction in enzyme activity.

Cathepsin D from R. philippinarum exhibited high thermostability up to 50°C and activity at pH 2-4. Its stability and characteristics are comparable to those of other species, which opens avenues in biotechnology for protein hydrolysis and peptide production.

The aim of this study was to investigate the expression characteristics and interrelationships of FNDC5 and pyroptosis-associated molecules in peripheral blood mononuclear cells of patients with coronary heart disease (CHD).

Patients were divided into stable angina (SA), unstable angina (UA), and acute myocardial infarction (AMI) groups based on different clinical symptoms. According to the Gensini score, they were then divided into mild, moderate, and severe lesion groups. The control (NC) group was also set. ELISA assay was employed to detect the levels of Irisin, IL-1β, and IL-18, and the levels of pyroptosis-associated molecules, NF-κB p50, NF-κB p65, and FNDC5 were detected and compared by qRT-PCR and Western blot (WB). Logistic regression and Spearman's partial correlation analysis were used to analyze the pathogenic factors of CHD and explore the interrelationships between FNDC5 and the molecules.

IL-1β and IL-18 of CHD patients were increased, while the Irisin was decreased. With the aggravation of symptoms and severity of coronary artery stenosis, the former increased, and the Irisin gradually decreased (P<0.05). About qRT-PCR and WB: With the aggravation of symptoms, the levels of pyroptosis-associated molecules and other indicators were increased, and FNDC5 was decreased (P<0.05). NLRP3, Caspase-1, and NF-κB p50 protein were positively correlated with the incidence of CHD, and FNDC5 was also negatively correlated with that of CHD. Even when common risk factors for CHD were taken into account, FNDC5 and NLRP3 were still found to be negatively connected.

The decreased expression level of FNDC5 and the increased level of pyroptosis-associated molecules may be related to CHD.

Gastric cancer has become one of the major diseases threatening human health. This study aimed to investigate the mechanism of an anticancer bioactive peptide (ACBP) combined with oxaliplatin (OXA) on MKN-45, SGC7901, and NCI-N87 differentiated human gastric cancer cells and GES-1 immortalized human gastric mucosal epithelial cells. The therapeutic effect and action mechanism of short-term intermittent ACBP combined with OXA on nude mice with human gastric cancer were also investigated.

The half-maximal inhibitory concentrations of these agents in these cells were measured by an MTT assay, and cell morphological changes were observed by H&E staining. The expression of Lin28, miR-107, miR-609, and Let-7 in these four cell lines was determined by q-PCR after drug treatment. Lin28 protein expression in these four cell lines treated with these drugs was measured by western blotting. Furthermore, activity and quality of life were observed daily in all tumor-bearing nude mice, and the expression of Lin28 in tumor tissue was determined by immunohistochemistry and RT-PCR.

The results showed that ACBP inhibited the proliferation of MKN-45, SGC7901, and NCI-N87 gastric cancer cells in a dose-dependent manner and weakly suppressed the proliferation of GES-1 cells. Moreover, its inhibitory effect on proliferation was stronger in poorly differentiated gastric cancer cells. ACBP, OXA, and the combination upregulated Lin28 gene expression in MKN-45 cells and downregulated it in SGC7901 and GES-1 cells. ACBP and the combination therapy downregulated Let-7 expression in MKN-45 cells and upregulated Let-7 expression in SGC7901 cells. The combination of ACBP with OXA demonstrated significant anticancer sensitization. Moreover, it also significantly improved the quality of life of tumor-bearing nude mice and reduced the toxic side effects of chemotherapeutic drugs on nude mice.

ACBP alone and in combination with oxaliplatin influenced the expression of tumor stem cell marker gene Lin28 and regulated the expression of microRNAs specifically regulated by Lin28. In addition, the anticancer effects and attenuated sensitization effects of ACBP may be related to the Lin28/miRNA-107 signaling pathway, acting by inhibiting the proliferation of cancerous stem cells. The findings of this study provide a scientific basis for exploring the antitumor mechanism of ACBP alone and combined with chemotherapeutic drugs.