Deltin 7

In humans, the dimeric receptor complex IFNAR2-IFNAR1 accelerates cellular response triggered by type I interferon (IFN) family proteins in response to viral infection including Coronavirus infection. Studies have revealed the association of the IFNAR2 gene with severe illness in Coronavirus infection and indicated the association of genomic variants, i.e. single nucleotide polymorphisms (SNPs). However, comprehensive analysis of SNPs of the IFNAR2 gene has not been performed in both coding and non-coding region to find the causes of loss of function of IFNAR2 in COVID-19 patients. In this study, we have characterized coding SNPs (nsSNPs) of IFNAR2 gene using different bioinformatics tools and identified deleterious SNPs. We found 9 nsSNPs as pathogenic and disease-causing along with a decrease in protein stability. We employed molecular docking analysis that showed 5 nsSNPs to decrease binding affinity to IFN. Later, MD simulations showed that P136R mutant may destabilize crucial binding with the IFN molecule in response to COVID-19. Thus, P136R is likely to have a high impact on disrupting the structure of the IFNAR2 protein. GTEx portal analysis predicted 14 sQTLs and 5 eQTLs SNPs in lung tissues hampering the post-transcriptional modification (splicing) and altering the expression of the IFNAR2 gene. sQTLs and eQTLs SNPs potentially explain the reduced IFNAR2 production leading to severe diseases. These mutants in the coding and non-coding region of the IFNAR2 gene can help to recognize severe illness due to COVID 19 and consequently assist to develop an effective drug against the infection.

Cancer stem cells (CSCs) are a specific type of cancer cell that can both self-renew and differentiate, playing a key role in cancer development and progression. Existing clinical biomarkers, however, are insufficient as robust biomarkers to be used in clinical practice for cancer patients due to their limited confirmation and contested prognostic relevance. Therefore, there is a large pool of potential biomarkers that have not been thoroughly explored. CSC surface biomarkers have recently been the focus of many studies in the clinical practice of cancer patients due to their potential utility in characterising the aetiology of cancer initiation, development, and metastasis. In this chapter, we discuss the most popular surface biomarkers of CSCs and provide their potential utility in cancer diagnosis and prognosis.

Nanobodies (Nbs) are great molecular tools that can circumvent the limitations of traditional antibodies such as large size, low stability, slow clearance, and high immunogenicity. Recent studies identified several clinical applications of Nbs targeting various cancers. Cancer stem cells (CSCs) comprise a limited subpopulation of cancer cells that can reproduce autonomously and differentiate into diverse cancer lineages. CSCs are responsible for providing resistance against chemotherapy and radiotherapy. Various studies focused on targeting these CSCs via Nbs to selectively reduce the cancer burden. Nbs have the potential to reduce the CSCs and thereby could halt the progression of specific cancers.

Combination strategies of KRAS inhibition with immunotherapy in treating advanced or recurrent colorectal carcinoma (CRC) may need to be assessed in circulating tumour cells (CTCs) to achieve better clinical outcomes. This study aimed to investigate the genomic variations of KRAS in CTCs and matched CRC tissues and compared mRNA expression of KRAS and CTLA-4 between wildtype and KRAS-mutated CTCs and CRC tissues. Clinicopathological correlations were also compared. Six known mutations of KRAS were identified at both codon 12 and codon 13 (c.35G>T/G12V, c.35G>A7/G12D, c.35G>C/G12A, c.34G>A/G12S, c.38G>C/G13A, and c.38G>A/G13D). Three CTC samples harboured the identified mutations (16.7%; 3/18), while fifteen matched primary tumour tissues (65.2%, 15/23) showed the mutations. CTCs harbouring the KRAS variant were different from matched CRC tissue. All the mutations were heterozygous. Though insignificant, CTLA-4 mRNA expression was higher in patients carrying KRAS mutations. Patients harbouring KRAS mutations in CTCs were more likely to have poorly differentiated tumours (p = 0.039) and with lymph node metastasis (p = 0.027) and perineural invasion (p = 0.014). KRAS mutations in CTCs were also significantly correlated with overall pathological stages (p = 0.027). These findings imply the genetic basis of KRAS with immunotherapeutic target molecules based on a real-time platform. This study also suggests the highly heterogeneous nature of cancer cells, which may facilitate the assessment of clonal dynamics across a single patient’s disease.

Serving as the interface between fetal and maternal circulation, the placenta plays a critical role in fetal growth and development. Placental exosomes are small membrane-bound extracellular vesicles released by the placenta during pregnancy. They contain a variety of biomolecules, including lipids, proteins, and nucleic acids, which can potentially be biomarkers of maternal diseases. An increasing number of studies have demonstrated the utility of placental exosomes for the diagnosis and monitoring of pathological conditions such as pre-eclampsia and gestational diabetes. This suggests that placental exosomes may serve as new biomarkers in liquid biopsy analysis. This review provides an overview of the current understanding of the biological function of placental exosomes and their potential as biomarkers of maternal diseases. Additionally, this review highlights current barriers and the way forward for standardization and validation of known techniques for exosome isolation, characterization, and detection. Finally, microfluidic devices for exosome research are discussed.

Colorectal carcinoma (CRC) is the third most common cancer in terms of diagnosis and the second in terms of mortality. Recent studies have shown that various proteins, such as extracellular vesicles (exosomes), specific genetic variants, gene transcripts, cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and altered epigenetic patterns, can be used to detect, and assess the prognosis of CRC. Over the last decade, a plethora of conventional methodologies (e.g., polymerase chain reaction [PCR], direct sequencing, enzyme-linked immunosorbent assay [ELISA], microarray, in situ hybridization) as well as advanced analytical methodologies (e.g., microfluidics, electrochemical biosensors, surface-enhanced Raman spectroscopy [SERS]) have been developed for analyzing genetic and epigenetic biomarkers using both optical and non-optical tools. Despite these methodologies, no gold standard detection method has yet been implemented that can analyze CRC with high specificity and sensitivity in an inexpensive, simple, and time-efficient manner. Moreover, until now, no study has critically reviewed the advantages and limitations of these methodologies. Here, an overview of the most used genetic and epigenetic biomarkers for CRC and their detection methods are discussed. Furthermore, a summary of the major biological, technical, and clinical challenges and advantages/limitations of existing techniques is also presented.

Detection of KRAS mutation in colorectal cancer (CRC) is important in the prediction of response to target therapy. The study aims to develop a novel mutation detection platform called the “PNA-LNA molecular switch” for the detection of KRAS mutation in CRC. We employed the enhanced binding specificity of peptide nucleic acid (PNA) and locked nucleic acid (LNA) in conjunction with a loop-mediated isothermal amplification (LAMP) approach to identify the mutation status of KRAS oncogene codon 12 (c.35G>T/G12V and c.35G>A/G12D) using synthetic oligonucleotides and colon cancer cell lines (Caco-2 and SW480). This method specifically blocked the amplification of the wild-type sequences while substantially amplifying the mutated ones, which was visualized by both colorimetric and fluorescence assays. We then checked the mutation profile of KRAS codon 12 in the DNA derived from tumor tissue samples (number of samples, n = 30) and circulating tumor cells (n = 24) from CRC patients. Finally, we validated the results by comparing them with the data obtained from DNA sequencing of colon tumors (n = 21) of the same CRC patients. This method showed excellent sensitivity (1 DNA copy/µl), reproducibility [relative standard deviation (%RSD) < 5%, for n=3], and linear dynamic range (1 ag/μl-10 pg/μl, R² = 0.94). This platform is significantly faster, relatively cheaper, has superior sensitivity and specificity, and does not require any high-end equipment. To conclude, this method has the potential to be translated into clinical settings for the detection of mutations in diverse diseases and conditions.

Aklima Khatun, Mai Furukawa, Ikki Tateishi, Hideyuki Katsumata, Mahmudul Hassan Suhag, Jahida Binte Islam, and Satoshi Kaneco. "Photocatalytic degradation of endocrine disrupting chemical 17-α ethinylestradiol by TiO2 nanoparticles under solar light irradiation." Environmental Processes 11, no. 1 (2024): 1.

Monir Uzzaman, Mahmudul Hassan Suhag, Hideyuki Katsumata, Ikki Tateishi, Mai Furukawa, and Satoshi Kaneco. "A graphitic carbon nitride photocatalyst with a benzene-ring-modified isotype heterojunction for visible-light-driven hydrogen production." Catalysis Science & Technology 14, no. 2 (2024): 267-278.

Mahmudul Hassan Suhag, Hideyuki Katsumata, Ikki Tateishi, Mai Furukawa, and Satoshi Kaneco. "Black Phosphorus-Doped Graphitic Carbon Nitride with aromatic Benzene rings for efficient photocatalytic hydrogen production." Langmuir 39, no. 37 (2023): 13121-13131.