Current Protein and Peptide Science - Volume 23, Issue 8, 2022

Background: Clodronate, a non-nitrogen-containing bisphosphonate (non-NBP), is intracellularly converted into non-hydrolyzable ATP analogs. Clodronate and its analogs impair normal cell functions, including the exocytosis process. However, how this occurs in mast cells is still not well characterized. Objective: To summarize the possible mechanisms of clodronate-mediated exocytosis inhibition in mast cells. Results: Non-NBPs display several possible mechanisms of exocytosis inhibition in various cell types, including vesicular nucleotide transporter (VNUT) and purinergic receptor inhibition. Inhibition of purinergic receptors has been shown in mast cells, but VNUT inhibition remains to be confirmed. Inhibition of protein prenylation by non-NBPs has also been shown; however, direct evidence of non-NBPs in prenylated exocytosis proteins is still contradictory. Finally, non-NBPs may inhibit mast cell exocytosis via impairment of protein pyrophosphorylation. This mechanism is less studied, and direct evidence of the involvement of pyrophosphorylated proteins in exocytosis is still lacking. Conclusion: Non-NBPs may affect mast cell exocytosis by interacting with purinergic receptors or VNUT or by preventing post-translational modifications of exocytosis protein(s), i.e., prenylation and pyrophosphorylation. The latter needs further investigation to provide direct evidence of a role for non- NBPs.

Nitric oxide (NO) is a small molecule produced by nitric oxide synthase (NOS) with various physio-pathological functions in the body. There are three main NOS isoforms, including the endothelial (eNOS), inducible (iNOS), and neuronal NOS (nNOS), that exist in the peripheral organs and nervous systems of humans and rodents. Moreover, NOS includes other identified NOS isoforms, such as retinal Muller glial cells (mNOS), mitochondrial (mtNOS), penile (PnNOS), testis-specific (TnNOS), and invertebrate Drosophila NOS (dNOS), which are the lesser-known types. It is proposed that the versatile functions of NOS isoforms depend on various NOS splice variant subtypes and their expression in the neural (e.g., brain, and spinal cord) and non-neuronal tissues (e.g., lung, kidney, liver, and GI tract). Therefore, this review summarizes the NOS subtypes, splice variants, targeted splicing expression in the body, and their proposed physio-pathological functions. At last, alternative NOS subtypes and isoforms, which have previously received scant attention, will be addressed in this article.

Acute myocardial infarction (AMI) is a threat to human life and physical health worldwide. Timely reperfusion is very important to limit infarct size and protect ischemic myocardium. Unfortunately, it has also caused severer myocardial damage, which is called “myocardial ischemia/ reperfusion injury (MIRI)”. There is no effective clinical treatment for it. Over the past two decades, biological studies of NF-ΚB have improved the understanding of MIRI. Nuclear Factor-ΚB (NF-ΚB) is a major transcription factor associated with cardiovascular health and disease. It is involved in the release of pro-inflammatory factors and apoptosis of cardiomyocytes. Recent studies have shown that inhibition of NF-ΚB plays a protective role in acute hypoxia and reperfusion injury. Here we review the molecular regulation of NF-ΚB in MIRI, better understanding of NF-ΚB signaling mechanisms related to inflammation and crosstalk with endogenous small molecules. We hope this review will aid in improving therapeutic approaches to clinical diagnosing. This review provides evidence for the role of NF-ΚB in MIRI and supports its use as a therapeutic target.

Nanomaterials have undergone rapid development in the last few decades, galvanized by the versatility of their functional attributes and many inherent advantages over bulk materials. The state of art experimental techniques to synthesize nanoparticles (NPs) from varied sources offers unprecedented opportunities for utilization and exploration of multifaceted biological activities. Such formulations demand a preliminary understanding of the interaction between NPs and biomolecules. Most of these interactions depend on the external morphology of the NPs, like the shape, size, charge and surface chemistry. In addition, most experimental techniques are limited to cellular-level data, without the atomistic details of mechanisms that lead to these interactions. Consequently, recent studies have determined these atomistic events through in-silico techniques, which provide a better understanding and integrative details of interactions between biomolecules and different NPs. Therefore, while delineating the protein-NPs interaction, it is imperative to define the consequences of nanomaterial’s introduction and derive data for the formulation of better therapeutic interventions. This review briefly discusses varied types of NPs, their potential applications and interactions with peptides and proteins.

Background: The roles of T-Box transcription factor (TBX2) in endometrial cancer are still not clear. This study was designed to explore the roles of TBX2 in endometrial cancer and the underlying mechanisms. Methods: The knockdown and overexpression of TBX2 in endometrial cancer cell lines were constructed by using lentivirus transduction. The xenograft animal model was established by using stable endometrial cancer cell lines. Cell viability was determined by the CCK-8 assay. The mRNA and protein levels of target genes were determined by using qPCR and Western blotting, respectively. ChIP assay was used to determine the interactions between TBX2 and nuclear factor erythroid 2-related factor 2 (NRF2). Results: The upregulation of TBX2 was observed in endometrial cancer tissues from patients with Cisplatin- resistance and Cisplatin-resistant cells. Interestingly, TBX2 regulated cell viability and Cisplatin resistance of endometrial cancer cells. In addition, the regulatory effects of TBX2 on chemo-resistance of endometrial cancer cells were associated with the NRF2 signaling pathways. Consistently, the endometrial cancer xenograft animal model revealed that TBX2 regulated tumor growth and Cisplatin resistance, and its regulatory effects were in part by the regulation of NRF2 signaling pathways. Conclusion: TBX 2 enhanced Cisplatin resistance of endometrial cancer by regulating the NRF2 signaling pathways.