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Cancer Innovation Apr 2024Biosimilars are biological drugs created from living organisms or that contain living components. They share an identical amino-acid sequence and immunogenicity. These... (Review)
Review
Biosimilars are biological drugs created from living organisms or that contain living components. They share an identical amino-acid sequence and immunogenicity. These drugs are considered to be cost-effective and are utilized in the treatment of cancer and other endocrine disorders. The primary aim of biosimilars is to predict biosimilarity, efficacy, and treatment costs; they are approved by the Food and Drug Administration (FDA) and have no clinical implications. They involve analytical studies to understand the similarities and dissimilarities. A biosimilar manufacturer sets up FDA-approved reference products to evaluate biosimilarity. The contribution of next-generation sequencing is evolving to study the organ tumor and its progression with its impactful therapeutic approach on cancer patients to showcase and target rare mutations. The study shall help to understand the future perspectives of biosimilars for use in gastro-entero-logic diseases, colorectal cancer, and thyroid cancer. They also help target specific organs with essential mutational categories and drug prototypes in clinical practices with blood and liquid biopsy, cell treatment, gene therapy, recombinant therapeutic proteins, and personalized medications. Biosimilar derivatives such as monoclonal antibodies like trastuzumab and rituximab are common drugs used in cancer therapy. produces more than six antibodies or antibody-derived proteins to treat cancer such as filgrastim, epoetin alfa, and so on.
PubMed: 38946928
DOI: 10.1002/cai2.115 -
Renal Failure Dec 2024Circular RNAs (circRNAs) have been shown to play critical roles in the initiation and progression of chronic glomerulonephritis (CGN), while their role from mesangial...
BACKGROUND
Circular RNAs (circRNAs) have been shown to play critical roles in the initiation and progression of chronic glomerulonephritis (CGN), while their role from mesangial cells in contributing to the pathogenesis of CGN is rarely understood. Our study aims to explore the potential functions of mesangial cell-derived circRNAs using RNA sequencing (RNA-seq) and bioinformatics analysis.
METHODS
Mouse mesangial cells (MMCs) were stimulated by lipopolysaccharide (LPS) to establish an model of CGN. Pro-inflammatory cytokines and cell cycle stages were detected by Enzyme-linked immunosorbent assay (ELISA) and Flow Cytometry experiment, respectively. Subsequently, differentially expressed circRNAs (DE-circRNAs) were identified by RNA-seq. GEO microarrays were used to identify differentially expressed mRNAs (DE-mRNAs) between CGN and healthy populations. Weighted co-expression network analysis (WGCNA) was utilized to explore clinically significant modules of CGN. CircRNA-associated CeRNA networks were constructed by bioinformatics analysis. The hub mRNAs from CeRNA network were identified using LASSO algorithms. Furthermore, utilizing protein-protein interaction (PPI), gene ontology (GO), pathway enrichment (KEGG), and GSEA analyses to explore the potential biological function of target genes from CeRNA network. In addition, we investigated the relationships between immune cells and hub mRNAs from CeRNA network using CIBERSORT.
RESULTS
The expression of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α was drastically increased in LPS-induced MMCs. The number of cells decreased significantly in the G1 phase but increased significantly in the S/G2 phase. A total of 6 DE-mRNAs were determined by RNA-seq, including 4 up-regulated circRNAs and 2 down-regulated circRNAs. WGCNA analysis identified 1747 DE-mRNAs of the turquoise module from CGN people in the GEO database. Then, the CeRNA networks, including 6 circRNAs, 38 miRNAs, and 80 mRNAs, were successfully constructed. The results of GO and KEGG analyses revealed that the target mRNAs were mainly enriched in immune, infection, and inflammation-related pathways. Furthermore, three hub mRNAs (BOC, MLST8, and HMGCS2) from the CeRNA network were screened using LASSO algorithms. GSEA analysis revealed that hub mRNAs were implicated in a great deal of immune system responses and inflammatory pathways, including IL-5 production, MAPK signaling pathway, and JAK-STAT signaling pathway. Moreover, according to an evaluation of immune infiltration, hub mRNAs have statistical correlations with neutrophils, plasma cells, monocytes, and follicular helper T cells.
CONCLUSIONS
Our findings provide fundamental and novel insights for further investigations into the role of mesangial cell-derived circRNAs in CGN pathogenesis.
Topics: RNA, Circular; Animals; Computational Biology; Mice; Mesangial Cells; Glomerulonephritis; Sequence Analysis, RNA; Gene Regulatory Networks; RNA, Messenger; Protein Interaction Maps; Chronic Disease; Cytokines; Lipopolysaccharides; Gene Expression Profiling; Disease Models, Animal
PubMed: 38946402
DOI: 10.1080/0886022X.2024.2371059 -
Genome Biology and Evolution Jul 2024Oecanthus is a genus of cricket known for its distinctive chirping and distributed across major zoogeographical regions worldwide. This study focuses on Oecanthus...
Oecanthus is a genus of cricket known for its distinctive chirping and distributed across major zoogeographical regions worldwide. This study focuses on Oecanthus rufescens, and conducts a comprehensive examination of its genome through genome sequencing technologies and bioinformatic analysis. A high-quality chromosome-level genome of O. rufescens was successfully obtained, revealing significant features of its genome structure. The genome size is 877.9 Mb, comprising 10 pseudo-chromosomes and 70 other sequences, with a GC content of 41.38% and an N50 value of 157,110,771 bp, indicating a high level of continuity. BUSCO assessment results demonstrate the genome's integrity and quality are high (of which 96.8% are single-copy and 1.6% are duplicated). Comprehensive genome annotation was also performed, identifying approximately 310 Mb of repetitive sequences, accounting for 35.3% of the total genome sequence, and discovering 15,481 tRNA genes, 4,082 rRNA genes, and 1,212 other non-coding genes. Furthermore, 15,031 protein-coding genes were identified, with BUSCO assessment results showing that 98.4% (of which 96.3% are single-copy and 1.6% are duplicated) of the genes were annotated.
PubMed: 38946321
DOI: 10.1093/gbe/evae145 -
Chemistry & Biodiversity Jun 2024G-quadruplex DNA sequences present in the promoter and telomere regions of the genomic sequence are considered therapeutic targets for the treatment of cancer. Curcumin,...
G-quadruplex DNA sequences present in the promoter and telomere regions of the genomic sequence are considered therapeutic targets for the treatment of cancer. Curcumin, derived from Curcuma longa, has been known as a quadruplex binder and has a potential role in the apoptosis of cancer cells. Here, we have reported the Schiff base ligand of curcumin synthesized through the condensation of the amino acid L-tryptophan and the knoevenagel derivative of curcumin (4-nitrobenzylidene curcumin (NBC)) as a potential G-quadruplex binder. Thus, spectroscopic and biophysical studies reveal a higher binding affinity of the ligand Sb-NBC towards the promoter and telomere G-quadruplex sequence as compared to the parent NBC. The ligand Sb-NBC highly stabilizes the parallel and hybrid G-quadruplex topologies to 10.5 0C- 6.4 0C. Interestingly, the ligands also exhibit selective cytotoxicity toward cancer cells over normal cells. Taken together, this work provides evidence of the possibility of applying curcumin Schiff base in cancer therapy to regulate oncogene expression in cancer cells.
PubMed: 38946104
DOI: 10.1002/cbdv.202400797 -
FEBS Letters Jun 2024The human FoxP transcription factors dimerize via three-dimensional domain swapping, a unique feature among the human Fox family, as result of evolutionary sequence...
The human FoxP transcription factors dimerize via three-dimensional domain swapping, a unique feature among the human Fox family, as result of evolutionary sequence adaptations in the forkhead domain. This is the case for the conserved glycine and proline residues in the wing 1 region, which are absent in FoxP proteins but present in most of the Fox family. In this work, we engineered both glycine (G) and proline-glycine (PG) insertion mutants to evaluate the deletion events in FoxP proteins in their dimerization, stability, flexibility, and DNA-binding ability. We show that the PG insertion only increases protein stability, whereas the single glycine insertion decreases the association rate and protein stability and promotes affinity to the DNA ligand.
PubMed: 38946055
DOI: 10.1002/1873-3468.14972 -
Iranian Biomedical Journal Apr 2024The growing threat of antibiotic resistance and Klebsiella pneumoniae infection in healthcare settings highlights the urgent need for innovative solutions, such as...
BACKGROUND
The growing threat of antibiotic resistance and Klebsiella pneumoniae infection in healthcare settings highlights the urgent need for innovative solutions, such as vaccines, to address these challenges. This study sought to assess the potential of using K. pneumoniae OmpA as a vaccine candidate through both in silico and in vivo analyses.
METHODS
The study examined the OmpA protein sequence for subcellular localization, antigenicity, allergenicity, similarity to the human proteome, physicochemical properties, B-cell epitopes, MHC binding sites, tertiary structure predictions, molecular docking, and immune response simulations. The ompA gene was cloned into the pET-28a (+) vector, expressed, purified and confirmed using Western blotting analysis. IgG levels in the serum of the immunized mice were measured using ELISA with dilutions ranging from 1:100 to 1:6400, targeting rOmpA and K. pneumoniae ATCC 13883. The sensitivity and specificity of the ELISA method were also assessed.
RESULTS
The bioinformatics analysis identified rOmpA as a promising vaccine candidate. The immunized group demonstrated significant production of specific total IgG antibodies against rOmpA and K. pneumoniae ATCC1 13883, as compared to the control group (p < 0.0001). The titers of antibodies produced in response to bacterial exposure did not show any significant difference when compared to the anti-rOmpA antibodies (p > 0.05). The ELISA test sensitivity was 1:3200, and the antibodies in the serum could accurately recognize K. pneumoniae cells.
CONCLUSION
This study is a significant advancement in the development of a potential vaccine against K. pneumoniae that relies on OmpA. Nevertheless, additional experimental analyses are required.
PubMed: 38946021
DOI: 10.61186/ibj.4023 -
Experimental & Molecular Medicine Jul 2024Recent substantial evidence implicating commensal bacteria in human diseases has given rise to a new domain in biomedical research: microbiome medicine. This emerging... (Review)
Review
Recent substantial evidence implicating commensal bacteria in human diseases has given rise to a new domain in biomedical research: microbiome medicine. This emerging field aims to understand and leverage the human microbiota and derivative molecules for disease prevention and treatment. Despite the complex and hierarchical organization of this ecosystem, most research over the years has relied on 16S amplicon sequencing, a legacy of bacterial phylogeny and taxonomy. Although advanced sequencing technologies have enabled cost-effective analysis of entire microbiota, translating the relatively short nucleotide information into the functional and taxonomic organization of the microbiome has posed challenges until recently. In the last decade, genome-resolved metagenomics, which aims to reconstruct microbial genomes directly from whole-metagenome sequencing data, has made significant strides and continues to unveil the mysteries of various human-associated microbial communities. There has been a rapid increase in the volume of whole metagenome sequencing data and in the compilation of novel metagenome-assembled genomes and protein sequences in public depositories. This review provides an overview of the capabilities and methods of genome-resolved metagenomics for studying the human microbiome, with a focus on investigating the prokaryotic microbiota of the human gut. Just as decoding the human genome and its variations marked the beginning of the genomic medicine era, unraveling the genomes of commensal microbes and their sequence variations is ushering us into the era of microbiome medicine. Genome-resolved metagenomics stands as a pivotal tool in this transition and can accelerate our journey toward achieving these scientific and medical milestones.
PubMed: 38945961
DOI: 10.1038/s12276-024-01262-7 -
Food Research International (Ottawa,... Aug 2024Food-grade biopolymer-based complexes are of particular interest in the field of biologic ingredient delivery owing to unique controlled-release properties. Herein,...
Food-grade biopolymer-based complexes are of particular interest in the field of biologic ingredient delivery owing to unique controlled-release properties. Herein, three calcium-loaded complexes using Antarctic krill protein (P) and pectin (HMP) with different blending sequences were designed, named P + Ca + HMP, P + HMP + Ca and HMP + Ca + P, respectively. The calcium-loaded capacity, structural properties, and in vitro gastrointestinal calcium release of the complexes were investigated. The results demonstrated that the calcium binding rate and content of the P + Ca + HMP complex were the highest, reaching to 90.3 % and 39.0 mg/g, respectively. Particularly, the P + Ca + HMP complex exhibited a more stable fruit tree-like structure. Furthermore, the structural analysis confirmed that the primary interaction forces involved hydrogen bond, electrostatic, hydrophobic and ionic bond interaction. Ultimately, the P + Ca + HMP complex demonstrated superior calcium delivery. In conclusion, a novel calcium delivery system was successfully developed based on optimized the self-assembly sequence, which held significant importance in promoting the high-value utilization of Antarctic krill protein and enhancing the in vitro bioaccessibility of calcium.
Topics: Pectins; Euphausiacea; Animals; Calcium; Proteins
PubMed: 38945608
DOI: 10.1016/j.foodres.2024.114589 -
The Journal of Biological Chemistry Jun 2024DNA-PKcs is a DNA damage sensor kinase with established roles in DNA double-strand break repair via non-homologous end joining. Recent studies have revealed additional...
DNA-PKcs is a DNA damage sensor kinase with established roles in DNA double-strand break repair via non-homologous end joining. Recent studies have revealed additional roles of DNA-PKcs in the regulation of transcription, translation, and DNA replication. However, the substrates through which DNA-PKcs regulates these processes remain largely undefined. Here we utilized quantitative phosphoproteomics to generate a high coverage map of DNA-PKcs signaling in response to ionizing radiation and mapped its interplay with the ATM kinase. Beyond the detection of the canonical S/T-Q phosphorylation motif, we uncovered a non-canonical mode of DNA-PKcs signaling targeting S/T-ψ-D/E motifs. Sequence and structural analyses of the DNA-PKcs substrate recognition pocket revealed unique features compared to closely related PIKK kinases that may explain its broader substrate preference. These findings expand the repertoire of DNA-PKcs and ATM substrates while establishing a novel preferential phosphorylation motif for DNA-PKcs.
PubMed: 38945450
DOI: 10.1016/j.jbc.2024.107513 -
International Journal of Biological... Jun 2024Small single-chain variable fragments (scFv) are promising biomolecules to inhibit and neutralize toxins and to act as antivenoms. In this work, we aimed to produce a...
Small single-chain variable fragments (scFv) are promising biomolecules to inhibit and neutralize toxins and to act as antivenoms. In this work, we aimed to produce a functional scFv-6009FV in the yeast Pichia pastoris, which inhibits the pure Cn2 neurotoxin and the whole venom of Centruroides noxius. We were able to achieve yields of up to 31.6 ± 2 mg/L in flasks. Furthermore, the protein showed a structure of 6.1 % α-helix, 49.1 % β-sheet, and 44.8 % of random coil by CD. Mass spectrometry confirmed the amino acid sequence and showed no glycosylation profile for this molecule. Purified scFv-6009FV allowed us to develop anti-scFvs in rabbits, which were then used in affinity columns to purify other scFvs. Determination of its half-maximal inhibitory concentration value (IC) was 40 % better than the scFvs produced by E. coli as a control. Finally, we found that scFv-6009FV was able to inhibit ex vivo the pure Cn2 toxin and the whole venom from C. noxius in murine rescue experiments. These results demonstrated that under the conditions assayed here, P. pastoris is suited to produce scFv-6009FV that, compared to scFvs produced by E. coli, maintains the characteristics of an antibody and neutralizes the Cn2 toxin more effectively.
PubMed: 38945343
DOI: 10.1016/j.ijbiomac.2024.133461