Current protein & peptide science最新文献

The dynamic nature of the cell wall or plasma membrane is extremely important for the various cellular functions. The rearrangement of the cytoskeleton within the cell is a crucial process that is coordinated by the Profilin (PFN) protein. PFN is a small, cytosolic protein whose molecular weight is around 14-17 kDa. Originally, PFN was identified as an actin-binding protein that regulates actin dynamics. However, several studies later reported that the interaction of PFN with certain cytosolic proteins has a role in membrane trafficking, development, motility, and signaling. Additionally, the alternatively spliced PFN isoforms are present in different tissues and govern neurological and developmental functions. A mutation in these isoforms can result in abnormalities in the functioning. These isoforms interact with different ligands with certain specificity. However, the structural and functional biology of these isoforms is still under investigation. This review comprehensively discusses the roles of PFN and its isoforms across diverse species, spanning prokaryotes, eukaryotes, and viruses. Future research efforts are crucial for elucidating novel aspects and enhancing our understanding of the molecular mechanisms governed by PFN and its isoforms.

β-lactam Antibiotics (BLA) are characterized by the presence of lactam rings, which are widely used and have a huge market scale. Currently, the production of BLA is primarily achieved through a chemical process, which introduces a large number of toxic compounds, resulting inrelatively high environmental costs. As a part of green chemistry, the enzymatic production of BLA is gaining attention because it is non-toxic and pollution-free. This review focuses on industrial enzymes for BLA biosynthesis, which is critical for understanding the reaction process and addressing the deficiencies of low enzyme stability and activity. In this work, a focused dataset of industrial enzymes involved in BLA biosynthesis was constructed, and the structural characteristics of these enzymes were analyzed based on substrate specificity. Subsequently, eight representative enzyme molecules from the database were selected for detailed analyses, particularly focusing on substrate recognition and action mechanisms. Finally, some suggestions for the semi-rational design of enzymes are put forward given the defects existing in BLA biosynthesis. This review not only partially reveals the structure-function relationship of industrial enzyme molecules used in BLA enzymatic synthesis, but also contributes to the semi-rational design of subsequent enzymes, showing certain theoretical significance and application value.

Introduction: One of the earliest illnesses that has been identified is tuberculosis (TB). The largest challenge in managing tuberculosis today is the growing number of individuals infected with TB bacilli, particularly those that are extensively and multidrug-resistant (MDR and XDR). However, by figuring out the resistance's molecular mechanism, Advanced molecular methods may be used to rapidly determine therapy plans. Combining Delamanid (DLM) with Bedaquiline (BDQ), one of the recently authorized medications, indicates that the therapy is effective.

Methods: We aim to investigate efflux-mediated resistance mechanisms in M. Tuberculosis by using quantitative real-time PCR to assess the expression level of mmpS5 and mmpL5.

Results: The median (M) and interquartile range (Iqr) of mmpL5 and mmpS5 expression varied from 5.65 to 9.01 and 7.95 to 10.74, respectively, when resistant strains were compared with sensitive ones. M and Iqr of mmpL5 and mmpS5 expression, however, ranged from 0.08-3.04 and 0.05- 1.61 for sensitive strains, correspondingly.

Discussion: Our findings have implications for the development of fast genotypic drug susceptibility testing (DST). Quantitative real-time PCR to measure the expression level of mmpS5 and mmpL5 of baseline and post-baseline isolates is important to track the development of BDQ and DLM resistance.

Conclusion: Thus, when developing anti-tuberculosis drugs, mycobacterial MmpS5-MmpL5 transporters should be taken into consideration early on, as they are an MDR-efflux system.

Introduction: One to two percent of women worldwide experience recurrent pregnancy loss (RPL), defined as the loss of two or more consecutive pregnancies before 20 weeks of gestation. Genetic factors, including variations in the FOXP3 gene, have been implicated in the unexplained etiology of RPL. This study aimed to identify and characterize novel genetic variants in exons 2 and 7 of the FOXP3 gene in South Indian women with idiopathic RPL and to analyze their potential impact on protein structure.

Materials and methods: This case-control study involved DNA extraction from 300 participants, including 150 recurrent pregnancy loss (RPL) cases and 150 non-recurrent pregnancy loss (NRPL) controls. Polymerase chain reaction (PCR) and Sanger sequencing were used to identify genetic variants. The identified single-nucleotide polymorphisms (SNPs) were analyzed for frequency differences between the RPL and control groups. Additionally, bioinformatics tools were employed to assess the structural impact of the identified mutations on the FOXP3 protein.

Results: Seven novel single-nucleotide polymorphisms (SNPs) were identified, with four SNPs (-11InsT, 206G>A in exon 2, and 433InsT, 726A>T in exon 7), showing significant frequency variations between RPL and NRPL groups. The modeled structures of FOXP3 apo and mutant proteins displayed similar structural features, including a DNA-binding domain. Molecular dynamics simulation studies revealed comparable stability between the apo and mutant forms of FOXP3.

Discussion: The identified mutations in the FOXP3 gene can potentially disrupt its critical immune- regulatory functions, leading to impaired immune tolerance during pregnancy, a key factor in the development of RPL. These mutations may alter the activity or stability of regulatory T cells, which are essential for maintaining pregnancy by preventing immune rejection of the fetus.

Conclusion: These findings provide new insights into the genetic underpinnings of idiopathic RPL and underscore the importance of genetic testing for a better understanding of this condition.

A complex condition called diabetes mellitus is characterized by insufficient or resistant insulin production. The incidence of diseases is rising quickly, placing a significant economic, social, and health burden on the modern world. Interventions in nutrition and improved physical activity could make a big difference in controlling this disease. Bioactive peptides obtained from natural sources have been linked to various therapeutic benefits. Several peptides with anti-diabetic potential may lower blood sugar levels, enhance insulin uptake, and inhibit vital enzymes involved in the onset and progression of diabetes. Many bioactive peptides with anti-diabetic properties have been discovered and validated. A more transparent comprehension of the underlying molecular mechanisms of these peptides will aid the development of new peptide-based pharmaceuticals. The objective of this review was to update our understanding of the genesis, structural features, and mechanism of action. The effects of bioactive peptides on vital enzymes and proteins, such as α- glucosidase, α-amylase, glucagon-like peptides, and dipeptidyl peptidase-IV, which are involved in managing glycaemic levels from carbohydrate consumption through blood glucose regulation, were also addressed. The information obtained through this study and industry endeavours should provide a better understanding and evaluation of the prospects of bioactive peptides with antidiabetic potential for blood glucose level management.

Introduction: Autoimmune Thyroiditis (AIT) is caused by defects in the immune system in people with a genetic predisposition to the disease. The most prevalent type of autoimmune thyroiditis is Hashimoto's thyroiditis (HT). The present article reviews the possible relationship between α2-macroglobulin levels and autoantibodies in patients suffering from Hashimoto's disease.

Methods: A total of 170 patients with Hashimoto's disease, categorized into subclinical (96 patients) and manifest (74 patients) forms, were enrolled in the study. The control group comprised 65 individuals without thyroid pathologies or other autoimmune diseases. The levels of α2-macroglobulin and autoantibodies, including both organ-specific and non-organ-specific, were determined in all study participants.

Results: Organ-specific antibody and α2-macroglobulin levels were elevated in all patients studied compared to controls. Analysis of organ non-specific antibody levels in patients revealed elevated levels of antibodies to double-stranded (native) DNA in both the subclinical and manifest groups of patients. There were no statistically significant differences in antibody levels to single-stranded (denatured) DNA between the total patient group and the control groups.

Discussion: The data obtained demonstrated that there is no significant correlation between α2-- macroglobulin levels and autoantibody titres, as well as the severity of autoimmune thyroiditis. This finding suggests that α2-macroglobulin may have an unlikely role in the pathogenesis or as a biomarker of disease activity, including in the presence of antibody-dependent cellular damage. Conversely, antibodies directed against double-stranded DNA have exhibited enhanced informativeness and can be regarded as potential markers of the severity of autoimmune thyroid lesions.

Conclusion: Consequently, α2-macroglobulin has no diagnostic value as an indicator of autoimmune process exacerbation in Hashimoto's thyroiditis. Conversely, the presence and level of antibodies to double-stranded DNA may offer a means to assess the severity of the disease and should be the focus of further studies as prognostic markers.

Introduction: This study aimed to investigate the role of glycosyltransferase-related genes (GRGs) in stomach adenocarcinoma (STAD) through bioinformatic analysis and experimental validation, exploring their potential as prognostic and therapeutic biomarkers.

Methods: We utilized datasets from TCGA-STAD and GSE26901 to establish training and validation cohorts. Prognostic gene signatures were constructed using differentially expressed genes and LASSO regression. Pathway associations were explored via Gene Set Enrichment Analysis (GSEA), and correlations with immune cell infiltration and immune checkpoint genes were analyzed using CIBERSORT, ESTIMATE, and TIDE. Drug sensitivity was assessed using Onco- Predict, and GRG expression was confirmed via qRT-PCR.

Results: We identified 20 GRGs as prognostic indicators in STAD, with 14 showing abnormal expression. A six-gene signature (B3GAT3, FUT2, GALNT15, GLT8D1, MGAT4C, and ST8SIA6) was constructed, demonstrating AUC values of 0.662, 0.702, and 0.711 in TCGASTAD for predicting overall survival at 1, 3, and 5 years, respectively. The risk score was significantly associated with reduced survival and identified as an independent prognostic marker. The GRG profile was found to be correlated with immune cell infiltration, immune checkpoint genes, and drug responsiveness.

Discussion: The study highlights the significance of GRGs in STAD prognosis and potential therapeutic applications. The GRG signature shows promise as a predictive biomarker, with implications for personalized medicine. Limitations include modest AUC values and the need for larger, diverse cohorts for validation. Future work should integrate multi-omics data and explore the roles of GRGs in immune modulation and drug sensitivity.

Conclusion: The GRG profile serves as a prognostic biomarker for STAD, offering new insights into therapeutic approaches and potential applications in other gastrointestinal cancers.

Circular RNAs, or circRNAs, play a key role in breast cancer biology, directly impacting the diagnosis, prognosis, and treatment of the disease. This review explores the mechanisms, regulatory roles, and functional significance of circRNAs in breast cancer. Overexpressed circRNAs regulate gene expression, cell cycle progression, and drug response in breast cancer. This process is facilitated by the interaction between small RNA molecules (miRNAs) and proteins that can bind to RNA (RBPs), which target the main messenger RNA (mRNA). Consequently, they influence gene expression, cellular proliferation, and drug resistance. Dysregulated circRNA expression contributes to breast cancer progression by promoting tumor aggressiveness and treatment resistance.

Introduction: An endocrine condition known as Poly-Cystic Ovarian Syndrome (PCOS) makes females of reproductive age more susceptible to insulin resistance, excessive levels of male hormones, and delayed ovulation. It is the main reason that stimulates infertility in females during their reproductive years. Thus, the objective of the present research is to determine whether oleogum resins derived from Boswellia serrata and Commiphora myrrh could be beneficial in the treatment of PCOS using a female animal model (Wistar rats) that were administered 1 mg/ kg of letrozole for induction of the disease.

Methods: A combination therapy of Boswellia serrata and Commiphora myrrh was used to study its effect on rat models administered letrozole (1mg/ kg), employed to induce PCOS. OECD Guidelines 407 and 423 were followed for toxicity studies.

Results: It was revealed that the polyherbal mixture is nontoxic and safe to use, according to the results. Furthermore, studies have investigated the potential of a combination of oleo-gum resins in the treatment of letrozole-induced PCOS using animal models. According to the information gathered, it was found that the prepared herbal mixture significantly affected the letrozole-induced PCOS rat models. Additionally, it seems to have potential benefits for PCOS-related hormonal and reproductive disorders.

Conclusion: The polyherbal mixture was considered safe for consumption at a dose concentration of under 2000 mg/ kg and can be used for an extended period. Additionally, the polyherbal mixture improved the outcome of the therapy of PCOS in rat models administered with letrozole (1mg/ kg) employed to induce PCOS.

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide, and need novel molecular targets for improved diagnosis and treatment. There are some potential new molecular targets for CVD treatment, including miRNAs, C-reactive protein, interleukins, fibrinogen, monocyte chemotactic protein-1, etc. One of the newer targets can be cell division control protein 42 homolog (Cdc42), a small GTPase of the Rho family, which has a significant role in cardiovascular physiology and pathology. This review focuses on demonstrating multifaceted functions of Cdc42 in cardiovascular complications, including vascular endothelial function, vascular smooth muscle cell regulation, cardiac myocyte development, inflammatory responses, and lipid metabolism. This review highlights the importance of Cdc42 in maintaining endothelial barrier integrity, regulating vascular smooth muscle cell phenotype, cardiac development, immune response modulation, and influencing lipid transport and insulin signalling. Furthermore, this review comprehensively explores the potential of Cdc42 as a biomarker for early CVD detection and proves to be a beneficial therapeutic target. This review also addresses the challenges in targeting Cdc42, given its ubiquitous nature, and directs future research, including tissue-specific modulation strategies and exploration of downstream signalling effectors. This review aims to potentiate future research by utilizing the current data on Cdc42 signalling in the cardiovascular system and constructing a bridge for innovative therapeutic approaches in CVD prevention and treatment. Cdc42 regulates cardiovascular processes, including endothelial function, vascular smooth muscle behaviour, cardiac development, inflammation, and metabolism. Additionally, evidence demonstrates Cdc42's involvement in key signalling pathways affecting lipid metabolism and insulin sensitivity.