Camels' biological fluids contained nanobodies: promising avenue in cancer therapy.

Cancer is a major health concern and accounts for one of the main causes of death worldwide. Innovative strategies are needed to aid in the diagnosis and treatment of different types of cancers. Recently, there has been an evolving interest in utilizing nanobodies of camel origin as therapeutic tools against cancer. Nanotechnology uses nanobodies an emerging attractive field that provides promises to researchers in advancing different scientific sectors including medicine and oncology. Nanobodies are characteristically small-sized biologics featured with the ability for deep tissue penetration and dissemination and harbour high stability at high pH and temperatures. The current review highlights the potential use of nanobodies that are naturally secreted in camels' biological fluids, both milk and urine, in the development of nanotechnology-based therapy for treating different typesQuery of cancers and other diseases. Moreover, the role of nano proteomics in the invention of novel therapeutic agents specifically used for cancer intervention is also illustrated.

BARD1 mystery: tumor suppressors are cancer susceptibility genes.

The full-length BRCA1-associated RING domain 1 (BARD1) gene encodes a 777-aa protein. BARD1 displays a dual role in cancer development and progression as it acts as a tumor suppressor and an oncogene. Structurally, BARD1 has homologous domains to BRCA1 that aid their heterodimer interaction to inhibit the progression of different cancers such as breast and ovarian cancers following the BRCA1-dependant pathway. In addition, BARD1 was shown to be involved in other pathways that are involved in tumor suppression (BRCA1-independent pathway) such as the TP53-dependent apoptotic signaling pathway. However, there are abundant BARD1 isoforms exist that are different from the full-length BARD1 due to nonsense and frameshift mutations, or deletions were found to be associated with susceptibility to various cancers including neuroblastoma, lung, breast, and cervical cancers. This article reviews the spectrum of BARD1 full-length genes and its different isoforms and their anticipated associated risk. Additionally, the study also highlights the role of BARD1 as an oncogene in breast cancer patients and its potential uses as a prognostic/diagnostic biomarker and as a therapeutic target for cancer susceptibility testing and treatment.

Identification and Characterization of Novel Mutations in Chronic Kidney Disease (CKD) and Autosomal Dominant Polycystic Kidney Disease (ADPKD) in Saudi Subjects by Whole-Exome Sequencing.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a condition usually caused by a single gene mutation and manifested by both renal and extrarenal features, eventually leading to end-stage renal disease (ESRD) by the median age of 60 years worldwide. Approximately 89% of ADPKD patients had either PKD1 or PKD2 gene mutations. The majority (85%) of the mutations are in the PKD1 gene, especially in the context of family history. Objectives: This study investigated the genetic basis and the undiscovered genes that are involved in ADPKD development among the Saudi population. Materials and Methods: In this study, 11 patients with chronic kidney disease were enrolled. The diagnosis of ADPKD was based on history and diagnostic images: CT images include enlargement of renal outlines, renal echogenicity, and presence of multiple renal cysts with dilated collecting ducts, loss of corticomedullary differentiation, and changes in GFR and serum creatinine levels. Next-generation whole-exome sequencing was conducted using the Ion Torrent PGM platform. Results: Of the 11 Saudi patients diagnosed with chronic kidney disease (CKD) and ADPKD, the most common heterozygote nonsynonymous variant in the PKD1 gene was exon15: (c.4264G > A). Two missense mutations were identified with a PKD1 (c.1758A > C and c.9774T > G), and one patient had a PKD2 mutation (c.1445T > G). Three detected variants were novel, identified at PKD1 (c.1758A > C), PKD2L2 (c.1364A > T), and TSC2 (deletion of a'a at the 3'UTR, R1680C) genes. Other variants in PKD1L1 (c.3813_381 4delinsTG) and PKD1L2 (c.404C > T) were also detected. The median age of end-stage renal disease for ADPK patients in Saudi Arabia was 30 years. Conclusion: This study reported a common variant in the PKD1 gene in Saudi patients with typical ADPKD. We also reported (to our knowledge) for the first time two novel missense variants in PKD1 and PKD2L2 genes and one indel mutation at the 3'UTR of the TSC2 gene. This study establishes that the reported mutations in the affected genes resulted in ADPKD development in the Saudi population by a median age of 30. Nevertheless, future protein−protein interaction studies to investigate the influence of these mutations on PKD1 and PKD2 functions are required. Furthermore, large-scale population-based studies to verify these findings are recommended.

Correction: Association of SNPs within TMPRSS6 and BMP2 genes with iron deficiency status in Saudi Arabia.

[This corrects the article DOI: 10.1371/journal.pone.0257895.].

The State-of-the-Art of Gene Editing and its Application to Viral Infections and Diseases Including COVID-19.

Gene therapy delivers a promising hope to cure many diseases and defects. The discovery of gene-editing technology fueled the world with valuable tools that have been employed in various domains of science, medicine, and biotechnology. Multiple means of gene editing have been established, including CRISPR/Cas, ZFNs, and TALENs. These strategies are believed to help understand the biological mechanisms of disease progression. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been designated the causative virus for coronavirus disease 2019 (COVID-19) that emerged at the end of 2019. This viral infection is a highly pathogenic and transmissible disease that caused a public health pandemic. As gene editing tools have shown great success in multiple scientific and medical areas, they could eventually contribute to discovering novel therapeutic and diagnostic strategies to battle the COVID-19 pandemic disease. This review aims to briefly highlight the history and some of the recent advancements of gene editing technologies. After that, we will describe various biological features of the CRISPR-Cas9 system and its diverse implications in treating different infectious diseases, both viral and non-viral. Finally, we will present current and future advancements in combating COVID-19 with a potential contribution of the CRISPR system as an antiviral modality in this battle.

Association of SNPs within TMPRSS6 and BMP2 genes with iron deficiency status in Saudi Arabia.

BACKGROUND: Globally, iron-deficiency anemia (IDA) remains a major health obstacle. This health condition has been identified in 47% of pre-school students (aged 0 to 5 years), 42% of pregnant females, and 30% of non-pregnant females (aged 15 to 50 years) worldwide according to the WHO. Environmental and genetic factors play a crucial role in the development of IDA; genetic testing has revealed the association of a number of polymorphisms with iron status and serum ferritin. AIM: The current study aims to reveal the association of TMPRSS6 rs141312 and BMP2 rs235756 with the iron status of females in Saudi Arabia. METHODS: A cohort of 108 female university students aged 18-25 years was randomly selected to participate: 50 healthy and 58 classified as iron deficient. A 3-5 mL sample of blood was collected from each one and analyzed based on hematological and biochemical iron status followed by genotyping by PCR. RESULTS: The genotype distribution of TMPRSS6 rs141312 was 8% (TT), 88% (TC) and 4% (CC) in the healthy group compared with 3.45% (TT), 89.66% (TC) and 6.89% (CC) in the iron-deficient group (P = 0.492), an insignificant difference in the allelic distribution. The genotype distribution of BMP2 rs235756 was 8% (TT), 90% (TC) and 2% (CC) in the healthy group compared with 3.45% (TT), 82.76% (TC) and 13.79% (CC) in iron-deficient group (P = 0.050) and was significantly associated with decreased ferritin status (P = 0.050). In addition, TMPRSS6 rs141312 is significantly (P<0.001) associated with dominant genotypes (TC+CC) and increased risk of IDA while BMP2 rs235756 is significantly (P<0.026) associated with recessive homozygote CC genotypes and increased risk of IDA. CONCLUSION: Our finding potentially helps in the early prediction of iron deficiency in females through the genetic testing.