Ala’a S. Shraim

The rapidly growing concern over the hazardous impact of phthalates on the environment and public health has led to a critical need for alternative and environmentally friendly plastics. Plasticizers developed from natural materials represent one possible solution. This paper explores four types of renewable feedstocks (sorbitol/polyols, glycerin, cardanol from cashew nutshell liquid, and limonene from citrus peels) as sources for developing alternative plasticizer systems. Key areas explored include the type of feedstock utilized, the methods used for extracting or processing the feedstocks, the nature of the chemical modification processes (e.g., esterification, epoxidation, etherification, or reactive grafting) applied to generate the respective plasticizers, and the resultant physical and mechanical properties. The performance of each plasticizer system in polymers such as PVC, PLA, and polysaccharide-based bioplastics is evaluated, alongside the compatibility with biological tissues, toxicological properties, biodegradability, and chemical migration into food simulants. The feasibility of each family of plasticizers is also assessed from an economic perspective, including availability of the feedstocks, economies of scale associated with large-volume production, and competitive pricing relative to established petroleum-derived plasticizers. Overall, sorbitol/polyol and glycerin derivative families have reached a level of maturity that provides a good balance of processability, food-contact safety, and biodegradability. Cardanol-based systems provide an attractive option where aromatic functional groups and combined plasticization–stabilization effects are needed. Limonene-derived plasticizer systems appear promising for use in PLA, but their broader utility may be limited by volatility, strong odors, and susceptibility to oxidation. Common issues identified across all four families include chemical migration into food products, regulatory approval, and the need for detailed life-cycle assessments.

The transient receptor potential melastatin (TRPM) family consists of eight members (TRPM1–8), which play a pivotal role in regulating cation fluxes, including K⁺, Na⁺, Ca²⁺, and Mg²⁺. While these channels are integral to various physiological functions, emerging evidence links TRPM dysregulation to the pathogenesis of colorectal cancer (CRC), one of the most prevalent and deadly malignancies worldwide. This review highlights the multifaceted roles of TRPM channels in CRC pathogenesis, their potential as diagnostic and prognostic biomarkers, and their therapeutic applications. Recent research has revealed that certain types of TRPM channels and specific noncoding RNAs within TRPM loci are implicated in critical oncogenic processes such as proliferation, migration, invasion, and epithelial-mesenchymal transition. Specific members, including TRPM4, TRPM7, and TRPM8, exhibit diverse effects in CRC, ranging from modulating metastasis to influencing chemoresistance. Despite their significant role in CRC, conflicting findings on TRPM expression levels in patient tissues highlight the complexity of their involvement and necessitate further research. TRPM modulators show therapeutic potential as anticancer agents. However, challenges in specificity and off-target effects currently limit their clinical application. Advancing our understanding of TRPM function in CRC could hold promise for novel treatment strategies to improve patient outcomes.

Sperm motility, a key determinant of male fertility, is often impaired by genetic variations affecting flagellar formation. The glutamine-rich protein 2 (QRICH2) gene encodes a protein essential for sperm flagella biogenesis and structural integrity. This study investigates genetic variations within exon 3 of the QRICH2 gene, identifying novel heterozygous variants associated with sperm tail-specific abnormalities and motility impairments. Among 34 individuals diagnosed with asthenozoospermia (ASZ) and 26 individuals with normal sperm parameters (NZ) from Jordan, eight unique heterozygous variants (c.123 G>T, c.133 G>C, c.138A>G, c.170A>C, c.189C>G, c.190T>C, c.195A>T, and c.204A>T) were exclusive to the ASZ group, while four variants (c.136 G>A, c.145A>C, c.179T>G, and c.180T>G) were found only in NZ. These variants were absent from major genetic databases, suggesting their potential novelty, while two variants (c.206C>T and c.189C>T) were linked to known SNP cluster IDs rs73996306 and rs1567790525, respectively. Four non-synonymous SNPs (c.136 G>A, c.145A>C, c.170A>C, and c.204A>T) were predicted to be functionally and structurally damaging, underscoring their significance. Additionally, five variants overlapped with previously reported mutation sites, indicating potential mutation hotspots. Statistical analysis revealed a significant association between QRICH2 mutations and tail defects (p < 0.021). These findings highlight the critical role of heterozygous QRICH2 mutations in mild-to-moderate ASZ, even in NZ individuals. Despite some carriers meeting WHO criteria for NZ, notable morphological abnormalities suggest the need for refined diagnostic benchmarks. Screening for QRICH2 mutations is essential for accurate molecular diagnosis and should be integrated into genetic counseling, particularly in regions like Jordan. Further research into the cumulative effects of heterozygous mutations and their environmental interactions is needed to expand our understanding of idiopathic male infertility and to enhance diagnostic and therapeutic strategies for male infertility.

Iron oxide nanozymes, which are magnetic nanoparticles with enzymatic properties, are explored, including their robust production techniques and diverse applications in the fields of biomedicine and environmental science.

Background: The national mandatory premarital screening test is based on mean corpuscular volume (MCV) > 80 fL value for the detection of b-thalassemia to provide acceptance for marriage. The objective of this study is to assess the efficacy of MCV as a screening test for b-thalassemia trait in the present population. Methods: This study was conducted on 418 blood samples collected from adult individuals. The diagnosis of b-thalassemia carrier was given to those having HbA2 values equal to or above 3.5%. The diagnostic reliability of different RBC indices and formulas in discriminating cases of b-thalassemia trait were evaluated. Finally, a new index called "Momani" was determined based on MCV, RDW and RBC count. Results: b-thalassemia trait was identified in 10% of the cases. The measured MCV value was significantly lower in b-thalassemia carrier group compared to non-carrier group (p = <0.001). MCV value and RBC count showed a higher diagnostic reliability than other RBC indices. We found that MCV ≤ 74.45 fL is more suitable cutoff value of MCV with 86.2% specificity, 71.4% sensitivity, 36.6% positive predictive value, and 96.4% negative predictive value. Finally, our index "Momani" was found to be useful in predicting carrier and paralleled the performance of Sirdah, Mentzer, and Ehsani indices. Conclusions: MCV<80 is a useful but not a perfect cutoff point for the screening of b-thalassemia carriers from noncarriers. The diagnostic accuracy of MCV can be improved by selecting a new cutoff value. Moreover, "Momani" index shows good discrimination ability in diagnosing b-thalassemia carrier in our population.

Aptamers are single-stranded oligonucleotides (RNA or DNA) with a typical length between 25 and 100 nucleotides which fold into three-dimensional structures capable of binding to target molecules. Specific aptamers can be isolated against a large variety of targets through efficient and relatively cheap methods, and they demonstrate target-binding affinities that sometimes surpass those of antibodies. Consequently, interest in aptamers has surged over the past three decades, and their application has shown promise in advancing knowledge in target analysis, designing therapeutic interventions, and bioengineering. With emphasis on their therapeutic applications, aptamers are emerging as a new innovative class of therapeutic agents with promising biochemical and biological properties. Aptamers have the potential of providing a feasible alternative to antibody- and small-molecule-based therapeutics given their binding specificity, stability, low toxicity, and apparent non-immunogenicity. This Review examines the general properties of aptamers and aptamer-protein interactions that help to understand their binding characteristics and make them important therapeutic candidates.

The c-KIT receptor represents an attractive target for cancer therapy. Aptamers are emerging as a new promising class of nucleic acid therapeutics. In this study, a conventional SELEX approach was applied against the kinase domain of a group of c-KIT proteins (c-KIT^WT, c-KIT^D816V, and c-KIT^D816H) to select aptamers from a random RNA pool that can bind to the kinase domain of each target with high affinity and can selectively interfere with their kinase activities. Interestingly, our data indicated that one candidate aptamer, called V15, can specifically inhibit the in vitro kinase activity of mutant c-KIT^D816V with an IC₅₀ value that is 9-fold more potent than the sunitinib drug tested under the same conditions. Another aptamer, named as H5/V36, showed the potential to distinguish between the c-KIT kinases by modulating the phosphorylation activity of each in a distinct mechanism of action and in a different potency.

[This corrects the article DOI: 10.1371/journal.pone.0189558.].

Aptamers are molecules that reveal highly complex and refined molecular recognition properties. These molecules are capable of binding with high affinity and selectivity to targets, ranging from small molecules to whole living cells. Several aptamers have been selected for targeting cellular proteins and they have also used in developing therapeutics and diagnostic strategies. Epithelial cell adhesion molecule (EpCAM) is considered as a cancer stem cell (CSC) biomarker and one of the most promising targets for aptamer selection against CSCs. In this study, we have developed a ssDNA aptamer with high affinity and selectivity of targeting the EpCAM protein extracellular domain. The SELEX technique was applied and the resulted sequences were tested on EpCAM-positive human gastric cancer cell line, KATO III, and the EpCAM-negative mouse embryonic fibroblast, NIH/3T3 cells. Ep1 aptamer was successfully isolated and showed selective binding on EpCAM-positive KATO III cells when compared to EpCAM-negative NIH/3T3 cells, as observed by the flow cytometry and the confocal imaging results. Additionally, the binding of Ep1 to EpCAM protein was assessed using mobility shifting assay and aptamers-protein docking. Furthermore, the binding affinity of Ep1 was measured against EpCAM protein using EpCAM-immobilized on magnetic beads and showed apparent affinity of 118 nM. The results of this study could suggest that Ep1 aptamer can bind specifically to the cellular EpCAM protein, making it an attractive ligand for targeted drug delivery and as an imaging agent for the identification of cancer cells.