Current Protein and Peptide Science - Volume 24, Issue 6, 2023

Hypoxia, a prevalent characteristic of both solid and liquid malignancies, is found to regulate how genes are expressed in a way that promotes cellular adaptability and survival. Metastasis is controlled by hypoxia-inducible factors (HIFs). HIFs are dimeric protein molecules made up of an oxygen (O2) responsive HIF-1α, HIF-2α, or HIF-3α domain and a periodically produced HIF-1β portion (also known as ARNT). Nevertheless, it is important to note that HIFs degrade under normoxic conditions. A large multitude of different biological operations, including vessels generation, oxygen delivery, stemness, pluripotency, multiplication, epithelial to mesenchymal shift, metastatic prevalence and intrusion, redox equilibrium, and programmed cell death, are strictly controlled by over 70 immediate HIF target genes that have been reported. Metabolic reprogramming, which modulates cellular energy generation aside from oxidative phosphorylation and concerning glycolysis, is among the core tasks of HIF target genes. As a result, choosing HIFs as a primary target in the treatment of various tumors is essential. We have a very limited understanding of this extremely complex topic, which is characterised by hypoxia- induced resistance. In order to combat this, scientists are investigating numerous cutting-edge approaches. Traditional chemotherapeutic drugs used to treat cancer are frequently linked to unfavourable side effects and the development of chemoresistance. The use of natural compounds in conjunction with chemotherapy drugs is rising as a result of their capacity to alter a number of molecular practices with a lower detrimental impact. Experimental and clinical research is accumulating evidence that phytochemicals can influence the genesis and progression of cancer by favourably modulating a number of signalling pathways. Combinations of phytochemicals are potent cancer treatment options because they incentivise apoptosis, limit cell prevalence, make cancerous cells more susceptible, and escalate immunity. Despite being characterised, HIF-1-independent mechanisms for medication resistance in hypoxia are still infrequently reported. The prime aim of the article is to summarise the most recent research on the molecular basis of hypoxia-induced chemoresistance and how chemotherapy and phytochemicals can be used to treat cancer patients who are resistant to drugs.

Epigenetic modulations are currently emerging as promising targets in metabolic diseases, including non-alcoholic fatty liver disease (NAFLD), for their roles in pathogenesis and therapeutic potential. The molecular mechanisms and modulation potential of histone methylation as a histone post-transcriptional modification in NAFLD have been recently addressed. However, a detailed overview of the histone methylation regulation in NAFLD is lacking. In this review, we comprehensively summarize the mechanisms of histone methylation regulation in NAFLD. We conducted a comprehensive database search in the PubMed database with the keywords 'histone', 'histone methylation', 'NAFLD', and 'metabolism' without time restriction. Reference lists of key documents were also reviewed to include potentially omitted articles. It has been reported that these enzymes can interact with other transcription factors or receptors under pro-NAFLD conditions, such as nutritional stress, which lead to recruitment to the promoters or transcriptional regions of key genes involved in glycolipid metabolism, ultimately regulating gene transcriptional activity to influence the expression. Histone methylation regulation has been implicated in mediating metabolic crosstalk between tissues or organs in NAFLD and serves a critical role in NAFLD development and progression. Some dietary interventions or agents targeting histone methylation have been suggested to improve NAFLD; however, there is still a lack of additional research and clinical translational relevance. In conclusion, histone methylation/demethylation has demonstrated an important regulatory role in NAFLD by mediating the expression of key glycolipid metabolism-related genes, and more research is needed in the future to explore its potential as a therapeutic target.

Most of the currently available knowledge about protein structure and function has been obtained from laboratory experiments. As a complement to this classical knowledge discovery activity, bioinformatics-assisted sequence analysis, which relies primarily on biological data manipulation, is becoming an indispensable option for the modern discovery of new knowledge, especially when large amounts of protein-encoding sequences can be easily identified from the annotation of highthroughput genomic data. Here, we review the advances in bioinformatics-assisted protein sequence analysis to highlight how bioinformatics analysis will aid in understanding protein structure and function. We first discuss the analyses with individual protein sequences as input, from which some basic parameters of proteins (e.g., amino acid composition, MW and PTM) can be predicted. In addition to these basic parameters that can be directly predicted by analyzing a protein sequence alone, many predictions are based on principles drawn from knowledge of many well-studied proteins, with multiple sequence comparisons as input. Identification of conserved sites by comparing multiple homologous sequences, prediction of the folding, structure or function of uncharacterized proteins, construction of phylogenies of related sequences, analysis of the contribution of conserved related sites to protein function by SCA or DCA, elucidation of the significance of codon usage, and extraction of functional units from protein sequences and coding spaces belong to this category. We then discuss the revolutionary invention of the "QTY code" that can be applied to convert membrane proteins into water- soluble proteins but at the cost of marginal introduced structural and functional changes. As machine learning has been done in other scientific fields, machine learning has profoundly impacted protein sequence analysis. In summary, we have highlighted the relevance of the bioinformatics-assisted analysis for protein research as a valuable guide for laboratory experiments.

Allergic diseases have increased worldwide during the last century and are a major disease burden globally. Several substances can induce allergic sensitization and elicit allergic symptoms in sensitized individuals. Pollen grains are one of the main causes of allergic rhinitis and asthma, and the prevalence of different pollen species depends on the climate, geographical regions, flora, and seasons. In addition to avoiding exposure to pollens, anti-allergic drugs are commonly used to mitigate the symptoms of allergies. However, these drugs need to be administered repeatedly as long as the symptoms prevail, usually life-long. Allergen immunotherapy (AIT) is currently the only disease-modifying approach that can prevent the natural progression of the disease (also known as an allergic march), provide a long-lasting therapeutic effect, and prevent the worsening of the symptoms and the occurrence of new sensitizations in allergic individuals. Since the pioneering clinical studies conducted more than 100 years ago using subcutaneously administered pollen extract to treat hay fever, significant advances have been made in the field of AIT. Starting from this pioneering approach, in this review, we have discussed the evolution of the products used for AIT with particular emphasis on pollen allergoids, the chemically modified pollen extracts characterized by lower allergenicity and comparable immunogenicity, and the different routes of administration used for AIT.

Trehalose, a disaccharide molecule of natural origin, is known for its diverse biological applications, like in drug development, research application, natural scaffold, stem cell preservation, food, and various other industries. This review has discussed one such diverse molecule ‘trehalose aka mycose’, and its diverse biological applications with respect to therapeutics. Due to its inertness and higher stability at variable temperatures, it has been developed as a preservative to store stem cells, and later, it has been found to have anticancer properties. Trehalose has recently been associated with modulating cancer cell metabolism, diverse molecular processes, neuroprotective effect, and so on. This article describes the development of trehalose as a cryoprotectant and protein stabilizer as well as a dietary component and therapeutic agent against various diseases. The article discusses its role in diseases via modulation of autophagy, various anticancer pathways, metabolism, inflammation, aging and oxidative stress, cancer metastasis and apoptosis, thus highlighting its diverse biological potential.

Background: A hallmark pathology of Alzheimer's disease (AD) is the construction of neurofibrillary tangles, which are made of hyperphosphorylated Tau. The cis-proline isomer of the pThr/Ser-Pro sequence has been suggested to act as an aggregation precursor according to the ‘Cistauosis’ hypothesis; however, this aggregation scheme is not yet completely approved. Various peptidyl-prolyl isomerases (PPIases) may specifically isomerize cis/trans-proline bonds and restitute Tau's ability to attach microtubules and may control Tau amyloid aggregation in AD. Methods: In this study, we provided experimental evidence for indicating the effects of the plant Cyclophilin (P-Cyp) from Platanus orientalis pollens on the Tau aggregation by various spectroscopic techniques. Results: Our findings disclosed that the rate/extent of amyloid formation in the Tau sample which is incubated with P-Cyp decreased and these observations do not seem to be due to the macromolecular crowding effect. Also, as proven that 80% of the prolines in the unfolded protein are in the trans conformation, urea-induced unfolding analyses confirmed this conclusion and showed that the aggregation rate/extent of urea-treated Tau samples decreased compared with those of the native protein. Also, XRD analysis indicated the reduction of scattering intensities and beta structures of amyloid fibrils in the presence of P-Cyp. Therefore, the ability of P-Cyp to suppress Tau aggregation probably depends on cis to trans isomerization of proline peptide bonds (X-Pro) and decreasing cis isomers in vitro. Conclusion: The findings of the current study may inspire possible protective/detrimental effects of various types of cyclophilins on AD onset/progression through direct regulation of intracellular Tau molecules and provides evidence that a protein from a plant source is able to enter the cell cytoplasm and may affect the behavior of cytoplasmic proteins.