Exploring the potential of silymarin-loaded nanovesicles as an effective drug delivery system for cancer therapy: in vivo, in vitro, and in silico experiments.

We aimed to perform a comprehensive study on the development and characterization of silymarin (Syl)-loaded niosomes as potential drug delivery systems. The results demonstrate significant novelty and promising outcomes in terms of morphology, size distribution, encapsulation efficiency, in vitro release behavior, free energy profiles of Syl across the niosome bilayer, hydrogen bonding interactions, antimicrobial properties, cytotoxicity, and in vivo evaluations. The physical appearance, size, and morphology assessment of free niosomes and Syl-loaded niosomes indicated stable and well-formed vesicular structures suitable for drug delivery. Transmission electron microscopy (TEM) analysis revealed spherical shapes with distinct sizes for each formulation, confirming uniform distribution. Dynamic light scattering (DLS) analysis confirmed the size distribution results with higher polydispersity index for Syl-loaded niosomes. The encapsulation efficiency of Syl in the niosomes was remarkable at approximately 91%, ensuring protection and controlled release of the drug. In vitro release studies showed a sustained release profile for Syl-loaded niosomes, enhancing therapeutic efficacy over time. Free energy profiles analysis identified energy barriers hindering Syl permeation through the niosome bilayer, emphasizing challenges in drug delivery system design. Hydrogen bonding interactions between Syl and niosome components contributed to energy barriers, impacting drug permeability. Antimicrobial assessments revealed significant differences in inhibitory effects against S. aureus and E. coli. Cytotoxicity evaluations demonstrated the superior tumor-killing potential of Syl-loaded niosomes compared to free Syl. In vivo studies indicated niosome formulations' safety profiles in terms of liver and kidney parameters compared to bulk Syl, showcasing potential for clinical applications. Overall, this research highlights the promising potential of Syl-loaded niosomes as effective drug delivery systems with enhanced stability, controlled release, and improved therapeutic outcomes.

IGF2BP2 and IGFBP3 Genotypes, Haplotypes, and Genetic Models Studies in Polycystic Ovary Syndrome.

BACKGROUND: Insulin resistance has been correlated with the genetic diversity within the insulin-like binding proteins genes. Moreover, insulin resistance is one of the key characteristics of the widespread reproductive endocrine condition known as polycystic ovarian syndrome (PCOS). Hence, this study is aimed to determine the association between IGFBP3 and IGF2BP2 gene variants and PCOS risk. METHODS: A total of 300 subjects (150 PCOS cases diagnosed based on Rotterdam ESHRE/ASRM consensus criteria and 150 healthy subjects) were recruited in this case-control cross-sectional study. Tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS-PCR) was used for genotyping rs11705701, whereas genotyping of rs1470579 and rs2854744 was done employing PCR-restriction fragment length polymorphism (PCR-RFLP) technique. RESULTS: The CC and AA+AC genotypes of rs1470579 conferred an increased risk of PCOS in our population. Regarding the rs2854744, an increased risk of PCOS was observed under the codominant homozygous (TT vs. GG) model by 2.54 fold. The C allele of rs1470579 and T allele of rs2854744 enhanced PCOS risk by 1.97 and 1.46 folds, respectively. Haplotype analysis showed that the Ars1470579Ars11705701 haplotype conferred a decreased risk of PCOS (odds ratio = 0.53, 95% confidence interval = 0.34-0.83, p = 0.006). The AC/GG/GT, AA/GA/GT, AC/GA/GG, and AC/GA/GT genotype combinations of rs1470579/rs11705701/rs2854744 were associated with a decreased risk of the disease. CONCLUSIONS: IGF2BP2 rs1470579 and IGFBP3 rs2854744 enhanced PCOS susceptibility in a Southeastern Iranian population. Further investigation involving larger cohorts representing diverse ethnic backgrounds is needed to confirm the current findings.

Nanotherapeutic approaches for delivery of long non-coding RNAs: an updated review with emphasis on cancer.

The long noncoding RNAs (lncRNAs) comprise a wide range of RNA species whose length exceeds 200 nucleotides, which regulate the expression of genes and cellular functions in a wide range of organisms. Several diseases, including malignancy, have been associated with lncRNA dysregulation. Due to their functions in cancer development and progression, lncRNAs have emerged as promising biomarkers and therapeutic targets in cancer diagnosis and treatment. Several studies have investigated the anti-cancer properties of lncRNAs; however, only a few lncRNAs have been found to exhibit tumor suppressor properties. Furthermore, their length and poor stability make them difficult to synthesize. Thus, to overcome the instability of lncRNAs, poor specificity, and their off-target effects, researchers have constructed nanocarriers that encapsulate lncRNAs. Recently, translational medicine research has focused on delivering lncRNAs into tumor cells, including cancer cells, through nano-drug delivery systems in vivo. The developed nanocarriers can protect, target, and release lncRNAs under controlled conditions without appreciable adverse effects. To deliver lncRNAs to cancer cells, various nanocarriers, such as exosomes, microbubbles, polymer nanoparticles, 1,2-dioleyl-3-trimethylammoniumpropane chloride nanocarriers, and virus-like particles, have been successfully developed. Despite this, every nanocarrier has its own advantages and disadvantages when it comes to delivering nucleic acids effectively and safely. This article examines the current status of nanocarriers for lncRNA delivery in cancer therapy, focusing on their potential to enhance cancer treatment.

Composition, preparation methods, and applications of nanoniosomes as codelivery systems: a review of emerging therapies with emphasis on cancer.

Nanoniosome-based drug codelivery systems have become popular therapeutic instruments, demonstrating tremendous promise in cancer therapy, infection treatment, and other therapeutic domains. An emerging form of vesicular nanocarriers, niosomes are self-assembling vesicles composed of nonionic surfactants, along with cholesterol or other amphiphilic molecules. This comprehensive review focuses on how nanosystems may aid in making anticancer and antibacterial pharmaceuticals more stable and soluble. As malleable nanodelivery instruments, the composition, types, preparation procedures, and variables affecting the structure and stability of niosomes are extensively investigated. In addition, the advantages of dual niosomes for combination therapy and the administration of multiple medications simultaneously are highlighted. Along with categorizing niosomal drug delivery systems, a comprehensive analysis of various preparation techniques, including thin-layer injection, ether injection, and microfluidization, is provided. Dual niosomes for cancer treatment are discussed in detail regarding the codelivery of two medications and the codelivery of a drug with organic, plant-based bioactive compounds or gene agents. In addition, niogelosomes and metallic niosomal carriers for targeted distribution are discussed. The review also investigates the simultaneous delivery of bioactive substances and gene agents, including siRNA, microRNA, shRNA, lncRNA, and DNA. Additional sections discuss the use of dual niosomes for cutaneous drug delivery and treating leishmanial infections, Pseudomonas aeruginosa, and Mycobacterium tuberculosis. The study concludes by delineating the challenges and potential routes for nanoniosome-based pharmaceutical codelivery systems, which will be useful for nanomedicine practitioners and researchers.

Nanomaterials-Based Targeting of Long Non-Coding RNAs in Cancer: A Cutting-Edge Review of Current Trends.

This review article spotlights the burgeoning potential of using nanotherapeutic strategies to target long non-coding RNAs (lncRNAs) in cancer cells. This updated discourse underlines the prominent role of lncRNAs in instigating cancer, facilitating its progression, and metastasis, validating lncRNAs' potential for being effective diagnostic biomarkers and therapeutic targets. The manuscript offers an in-depth examination of different strategies presently employed to modulate lncRNA expression and function for therapeutic purposes. Among these strategies, Antisense Oligonucleotides (ASOs), RNA interference (RNAi) technologies, and the innovative clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing tools garner noteworthy mention. A significant section of the review is dedicated to nanocarriers and their crucial role in drug delivery. These nanocarriers' efficiency in targeting lncRNAs in varied types of cancers is elaborated upon, validating the importance of targeted therapy. The manuscript culminates by reaffirming the promising prospects of targeting lncRNAs to enhance the accuracy of cancer diagnosis and improve treatment efficacy. Consequently, new paths are opened to more research and innovation in employing nanotherapeutic approaches against lncRNAs in cancer cells. Thus, this comprehensive manuscript serves as a valuable resource that underscores the vital role of lncRNAs and the various nano-strategies for targeting them in cancer treatment. Future research should also focus on unraveling the complex regulatory networks involving lncRNAs and identifying fundamental functional interactions to refine therapeutic strategies targeting lncRNAs in cancer.

Biomedical applications of cerium vanadate nanoparticles: a review.

Cerium vanadate nanoparticles (CeVO4 NPs), which are members of the rare earth orthovanadate nanomaterial family, have generated considerable interest due to their diverse properties and prospective biomedical applications. The current study, which provides a comprehensive overview of the synthesis and characterization techniques for CeVO4 NPs, emphasizes the sonochemical method as an efficient and straightforward technique for producing CeVO4 NPs with tunable size and shape. This paper investigates the toxicity and biocompatibility of CeVO4 NPs, as well as their antioxidant and catalytic properties, which allow them to modify the redox state of biological systems and degrade organic pollutants. In addition, the most recent developments in the medicinal applications of CeVO4 NPs, such as cancer treatment, antibacterial activity, biosensing, and drug or gene delivery, are emphasized. In addition, the disadvantages of CeVO4 NPs, such as stability, aggregation, biodistribution, and biodegradation, are outlined, and several potential solutions are suggested. The research concludes with data and recommendations for developing and enhancing CeVO4 NPs in the biomedical industry.

Association of Genetic Polymorphisms in Long Noncoding RNA HOTTIP with Risk of Idiopathic Recurrent Spontaneous Abortion.

The clustered homeobox gene family known as the Hox family plays a fundamental role in the morphogenesis of the vertebrate's embryo. A long noncoding RNA (lncRNA), known as HOTTIP (HOXA transcript at the distal tip), has been functionally characterized and contributed to the pathogenesis of various conditions. The current case-control study was undertaken to examine the gene frequencies and shared alleles of the HOTTIP  gene in Iranian participants with or without idiopathic recurrent spontaneous abortion (RSA). Both ARMS-PCR reaction and RFLP-PCR techniques were employed to detect three HOTTIP polymorphisms (rs2023843C/T, rs78248039A/T, and rs1859168C/A) in a DNA sample of 161 women with RSA and 177 healthy women. We found that the TT genotype of the HOTTIP rs2023843 C/T polymorphism was associated with a lower risk for idiopathic RSA. In contrast, the TT genotype of the HOTTIP rs78248039 A/T polymorphism was correlated with an enhanced risk of RSA. The presence of the A-allele for HOTTIP rs1859168 C/A polymorphism was associated with an increased risk for idiopathic RSA. Haplotype analysis showed that the T/T/A, C/T/A, T/T/C, and T/A/A haplotypes of rs2023843/rs78248039/rs1859168 enhanced RSA susceptibility. Computational analysis predicted that this lncRNA might act as a potential sponge for some microRNAs; therefore, affecting the expression of genes being targeted by them. In addition, both rs2023843 and rs1859168 variants could alter the local secondary structure of HOTTIP. Our results showed that HOTTIP rs2023843C/T, rs78248039A/T, and rs1859168C/A polymorphisms may confer genetic susceptibility to idiopathic RSA in an Iranian population.

The future opportunities and remaining challenges in the application of nanoparticle-mediated hyperthermia combined with chemo-radiotherapy in cancer.

A pivotal cause of death in the modern world, cancer is an insidious pathology that should be diagnosed at an early stage for successful treatment. Development of therapeutic interventions with minimal invasiveness and high efficacy that can discriminate between tumor and normal cells is of particular interest to the clinical science, as they can enhance patient survival. Nanoparticles are an invaluable asset that can be adopted for development of such diagnostic and therapeutic modalities, since they come in very small sizes with modifiable surface, are highly safe and stable, and can be synthesized in a controlled fashion. To date, different nanoparticles have been incorporated into numerous modalities such as tumor-targeted therapy, thermal therapy, chemotherapy, and radiotherapy. This review article seeks to deliver a brief account of recent advances in research and application of nanoparticles in hyperthermia-based cancer therapies. The most recent investigations are summarized to highlight the latest advances in the development of combined thermo-chemo-radiotherapy, along with the challenges associated with the application of nanoparticles in cancer therapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Nanotechnology-Based Strategies for Extended-Release Delivery of Angiotensin Receptor Blockers (ARBs): A Comprehensive Review.

There has been a significant shift in the perception of hypertension as an important contributor to the global disease burden. Approximately 6 % and 8 % of pregnancies are affected by hypertension, which can adversely affect the mother and the fetus. Furthermore, a hypertensive individual is at increased risk of developing kidney disease, arterial hardening, eye damage, and strokes. Using angiotensin receptor blockers (ARBs) is widespread in treating hypertension, heart failure, coronary artery disease, and diabetic nephropathy. Despite this, some ARBs have limited use due to their poor oral bioavailability and water solubility. To tackle this, a variety of nanoparticle (NP)-based systems, such as polymeric NPs (i. e., dendrimers), polymeric micelles, polymer-drug conjugates, lipid NPs, nanoemulsions, self-emulsifying drug delivery systems (SEDDS), solid lipid NPs (SLNs), nanostructured lipid carriers (NLCs), carbon-based nanocarriers, inorganic NPs, and nanocrystals, have been recently developed for efficient delivery of losartan, Valsartan (Val), Olmesartan (OLM), Telmisartan (TEL), Candesartan, Eprosartan, Irbesartan, and Azilsartan to target cells. This review article provides a literature-based comparison of the various classes of ARBs, their mechanisms of action, and an overview of the nanoformulations developed for ARB delivery and successfully applied to managing hypertension, diabetic complications, and other conditions.

Plasma microRNA-195, -34c, and - 1246 as novel biomarkers for the diagnosis of trastuzumab-resistant HER2-positive breast cancer patients.

Recently, miRNAs have been regarded as potential candidates for mediating therapeutic functions by targeting genes related to drug response. In this study, we suggested that plasma miRNAs may be correlated with response to trastuzumab in HER2-positive breast cancer patients. To determine whether miR-195, miR-23b-3p, miR-1246, and miR-34c-3p are involved in trastuzumab resistance, we screened their expressions in the BT-474 cell line, which was followed by plasma analysis from 20 trastuzumab-resistant HER2-positive breast cancer patients and 20 nonresistance subjects. Then, TargetScan, Pictar, and miRDB were applied to find the possible targets of the selected miRNAs. In addition, the expression status of admitted targets was evaluated. Our results showed that in resistant BT-474 cells, miR-1246, and miR-23b-3p were significantly upregulated, and miR-195-5p and miR-34c-3p were downregulated. In plasma analysis, we found miR-195-5p, miR-34c-3p, and miR-1246 meaningfully diminished in the resistant group, while the expression of miR-23b-3p was not statistically different. The expression levels of confirmed targets by qRT-PCR showed that the expression of RAF1, AKT3, c-MET, CCND1, PHLPP2, MYB, MAP2K1, and PTEN was significantly upregulated, while the expression of CCNG2 was significantly downregulated. The networks of miRNAs with their confirmed targets improved comprehension of miRNA-mediated therapeutic responses to trastuzumab and might be proposed for more characterization of miRNA functions. Moreover, these data indicated that miR-195-5p, miR-34c-3p, and miR-1246 could be possible biomarkers for prognosis and early detection of the trastuzumab-resistant group from the sensitive group of HER2-positive breast cancer patients.

Aptamer-functionalized quantum dots as theranostic nanotools against cancer and bacterial infections: A comprehensive overview of recent trends.

Aptamers (Apts) are synthetic nucleic acid ligands that can be engineered to target various molecules, including amino acids, proteins, and pharmaceuticals. Through a series of adsorption, recovery, and amplification steps, Apts are extracted from combinatorial libraries of synthesized nucleic acids. Using aptasensors in bioanalysis and biomedicine can be improved by combining them with nanomaterials. Moreover, Apt-associated nanomaterials, including liposomes, polymeric, dendrimers, carbon nanomaterials, silica, nanorods, magnetic NPs, and quantum dots (QDs), have been widely used as promising nanotools in biomedicine. Following surface modifications and conjugation with appropriate functional groups, these nanomaterials can be successfully used in aptasensing. Advanced biological assays can use Apts immobilized on QD surfaces through physical interaction and chemical bonding. Accordingly, modern QD aptasensing platforms rely on interactions between QDs, Apts, and targets to detect them. QD-Apt conjugates can be used to directly detect prostate, ovarian, colorectal, and lung cancers or simultaneously detect biomarkers associated with these malignancies. Tenascin-C, mucin 1, prostate-specific antigen, prostate-specific membrane antigen, nucleolin, growth factors, and exosomes are among the cancer biomarkers that can be sensitively detected using such bioconjugates. Furthermore, Apt-conjugated QDs have shown great potential for controlling bacterial infections such as Bacillus thuringiensis, Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Campylobacter jejuni, Staphylococcus aureus, and Salmonella typhimurium. This comprehensive review discusses recent advancements in the design of QD-Apt bioconjugates and their applications in cancer and bacterial theranostics.

An update in the applications of exosomes in cancer theranostics: from research to clinical trials.

Exosomes are nanosized extracellular vesicles secreted by nearly all viable cells following the fusing of multivesicular bodies and the plasma membrane and discharged into the encircling bodily fluids. Exosomes can transport cell-specific components from the source cell to the target cell. Given the enormous potential of exosomes as non-invasive diagnostic biomarkers and therapeutic nanovehicles. Lately, accumulated evidence has demonstrated that exosomes serve an important role in prognosis, diagnosis, and even treatment strategies. While several reviews have collective information on the biomedical application of exosomes, a comprehensive review incorporating updated and improved methodologies for beneficial applications of such vesicles in cancer theranostics is indispensable. In the current review, we first provided a comprehensive review of the introduction of exosomes, featuring their discovery, separation, characterization, function, biogenesis, secretion. The implications of exosomes as promising nanovehicles for drug and gene delivery, application of exosome inhibitors in the management of cancers, completed and ongoing clinical trials on the biological relevance of exosomes are then discussed in detail. As the field of exosome research grows, a better understanding of the subcellular parts and mechanisms involved in exosome secretion and targeting of specific cells will help figure out what their exact physiological functions are in the body.

Association of SLC11A1 polymorphisms with anthropometric and biochemical parameters describing Type 2 Diabetes Mellitus.

Diabetes, a leading cause of death globally, has different types, with Type 2 Diabetes Mellitus (T2DM) being the most prevalent one. It has been established that variations in the SLC11A1 gene impact risk of developing infectious, inflammatory, and endocrine disorders. This study is aimed to investigate the association between the SLC11A1 gene polymorphisms (rs3731864 G/A, rs3731865 C/G, and rs17235416 + TGTG/- TGTG) and anthropometric and biochemical parameters describing T2DM. Eight hundred participants (400 in each case and control group) were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and amplification-refractory mutation system-PCR (ARMS-PCR) methods. Lipid profile, fasting blood sugar (FBS), hemoglobin A1c level, and anthropometric indices were also recorded for each subject. Findings revealed that SLC11A1-rs3731864 G/A, -rs17235416 (+ TGTG/- TGTG) were associated with T2DM susceptibility, providing protection against the disease. In contrast, SLC11A1-rs3731865 G/C conferred an increased risk of T2DM. We also noticed a significant association between SLC11A1-rs3731864 G/A and triglyceride levels in patients with T2DM. In silico evaluations demonstrated that the SLC11A2 and ATP7A proteins also interact directly with the SLC11A1 protein in Homo sapiens. In addition, allelic substitutions for both intronic variants disrupt or create binding sites for splicing factors and serve a functional effect. Overall, our findings highlighted the role of SLC11A1 gene variations might have positive (rs3731865 G/C) or negative (rs3731864 G/A and rs17235416 + TGTG/- TGTG) associations with a predisposition to T2DM.

Biomedical applications of aptamer-modified chitosan nanomaterials: An updated review.

Among polysaccharides of environmental and economic interest, chitosan (CS) is receiving much attention, particularly in the food and biotechnology industries to encapsulate active food ingredients and immobilize enzymes. CS nanoparticles (CS NPs) combine the intrinsic beneficial properties of both natural polymers and nanoscale particles such as quantum size effect, biocompatibility, biodegradability, and ease of modification, possessing enhanced capacity for bioimaging, drug delivery, and biosensing applications. Aptamers are single-stranded oligonucleotides that can fold into predetermined structures and bind to the corresponding biomolecules. They are mainly used as targeting ligands in biosensors, disease diagnostic kits, and treatment strategies. They can deliver contrast agents and drugs into cancer cells and tissues, control microorganism growth, and also precisely target pathogens. Aptamer-conjugated CS NPs can significantly improve the efficacy of conventional therapies, minimize their side effects on normal tissues, and overcome the enhanced permeability retention (EPR) effect. Further, aptamer-conjugated carbohydrate-based nanobiopolymers have shown excellent antibacterial and antiviral properties and can be used to develop novel biosensors for the efficient detection of antibiotics, toxins, and other biomolecules. This updated review aims to provide a comprehensive overview of the bioapplications of aptamer-conjugated CS NPs used as innovative diagnostic and therapeutic platforms, their limitations, and potential future directions.

Relationship Between Genetic Polymorphisms in Cell Cycle Regulatory Gene TP53 and Polycystic Ovarian Syndrome: A Case-Control Study and In Silico Analyses.

Polycystic ovarian syndrome (PCOS) is a complex endocrine and metabolic condition with several potential causes. Insulin resistance is a hallmark of PCOS that often coexists with hirsutism, hyperandrogenism, being overweight, and hormonal imbalances. The functioning of multiple replication and transcription factors is regulated by tumor suppressor genes (TSGs), which play a crucial role in maintaining genomic integrity and controlling the cell cycle of granulosa cells. In the present study, we examined how three single nucleotide polymorphisms (SNPs) in TP53, a cell cycle regulatory gene, affect the risk of developing PCOS in a sample of an Iranian population. Genomic DNA was extracted from 200 PCOS patients and 200 healthy women to analyze TP53 rs17880604, rs1625895, and rs1042522 SNPs using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Our findings revealed that the majority of PCOS cases were overweight [25 < body mass index (BMI) < 30]. A positive association was observed between the TP53 rs1042522 SNP and the risk of PCOS under codominant heterozygous and overdominant genetic patterns (odds ratio > 1). Meanwhile, a negative association was observed between TP53 SNPs (rs1625895, rs17880604) and susceptibility to PCOS under codominant heterozygous and dominant models of inheritance (odds ratio < 1). Moreover, different genotype and haplotype combinations of rs17880604/rs1625895/rs1042522 conferred a decreased risk of PCOS in our population. We found no statistical difference in the frequency of TP53 genotypes between PCOS cases and/or controls in terms of BMI, waist circumference, prolactin level, and markers of lipid and carbohydrate profile (P > 0.05). Molecular dynamic prediction showed that the missense substitution in the 17p13.1 position (rs1042522) could change the properties and secondary structure of the p53 protein. As inherited risk factors, TP53 variations may play a  pivotal role in the pathogenesis of PCOS among Iranian women. Replicated population-based studies on other ethnicities are required to find the genetic contribution of variants of TP53, or SNPs located in other TSGs, to the etiology of this endocrine disease.

Association study to evaluate Foxo1 and Foxo3 gene polymorphisms in polycystic ovary syndrome: a preliminary case-control study and in silico analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is known as a multifactorial and multi-gene-mediated endocrine disorder among women of reproductive age. FoxO1 and FoxO3 are members of the forkhead transcriptional factors family that play a pivotal role in the function of ovaries. The current work is aimed at investigating the association between gene variants of FoxO1 and FoxO3 and the risk of PCOS in a sample of the Iranian population. METHODS AND RESULTS: We recruited 200 women diagnosed with PCOS and 200 healthy women. Both polymerase PCR-RFLP and ARMS-PCR methods were used for genotyping. Sanger sequencing was recruited to confirm the genotyping results. The T allele of rs17592236 and the C allele of rs12585277 decreased PCOS risk by 29 and 28%, respectively. In contrast, the C allele of rs2253310 and G allele of rs2802292 increased the risk of PCOS by 1.39 and 1.63 folds, correspondingly. Bioinformatics results showed that some genes, including matrix metallopeptidase 9 (MMP-9), phosphoinositide-3-Kinase Regulatory Subunit 224 1 (PIK3R1), peroxisome proliferator-activated receptor Gamma (PPARG), and glycogen synthase 225 kinase-3 beta (GSK-3 beta) have significant interactions with FoxO1, suggesting that FoxO1 might have crucial roles in regulating different signaling pathways in ovarian cells. CONCLUSION: We found that FoxO1 rs17592236C > T and rs12585277C > T had a protective role against PCOS, while FoxO3 rs2253310C > G and rs2802292G > T  enhanced the risk of this metabolic disorder in our population. Additional studies on larger populations with varying races are needed to confirm these findings.

Development and classification of RNA aptamers for therapeutic purposes: an updated review with emphasis on cancer.

Today, RNA aptamers are being considered promising theranostic tools against a wide variety of disorders. RNA aptamers can fold into complex shapes and bind to diverse nanostructures, macromolecules, cells, and viruses. It is possible to isolate RNA aptamers from a vast pool of nucleic acids via the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) method. As therapeutics, aptamers have great potential because of their ability to bind to proteins and selectively limit their activities with negligible side effects. Several RNA aptamers with potential implications in cancer diagnosis are known to confer a great affinity for single-stranded DNA molecules, long non-coding RNAs, circulating tumor cells, vascular endothelial growth factors, and tissue and sera-derived exosomes in patients with different malignancies. Furthermore, clinical investigations have revealed the efficacy of RNA aptamer-based agents in imaging modalities. This review seeks to deliver new insights into the development, classification, nanomerization, and modification of RNA aptamers, as well as their applications in cancer theranostics. The aptamers' mechanism of action and their interest to clinical trials as theranostic agents are also discussed.

Genetic Polymorphisms in miR-137 and Its Target Genes, TCF4 and CACNA1C, Contribute to the Risk of Bipolar Disorder: A Preliminary Case-Control Study and Bioinformatics Analysis.

Accumulating evidence has suggested that miR-137 and its target genes, CACNA1C, and TCF4, are amongst the most robustly implicated genes in psychiatric disorders. This preliminary study is aimed at investigating the effects of genetic variations in miR-137 (rs1625579A/C), TCF4 (rs1261084C/T), and CACNA1C (rs10774053A/G and rs10466907G/T) on BD susceptibility. We recruited 252 BD patients and 213 healthy subjects as the control group. Genotyping was performed using PCR-RFLP and ARMS-PCR methods. Enhanced risk of BD was found under the codominant homozygous, dominant, and allelic models of TCF4 rs1261084C/T, codominant homozygous and allelic models of CACNA1C rs10466907G/T polymorphisms, as well as codominant homozygous, dominant, recessive, and allelic models of the CACNA1C rs10774053A/G. Moreover, both TT/AG/GT/AA and TT/GG/GT/AC genotype combinations strongly increased the risk of BD in the participants. The bioinformatics analyses revealed that rs1261084C/T and rs10466907G/T created and disrupted binding sites of some miRNAs in the 3'-untranslated region of TCF4 and CACNA1C genes. In contrast, the rs10774053A/G created a new binding site for a major splicing factor and might have an effective role in the function of the CACNA1C protein. We have found that all the studied SNPs are positively associated with BD susceptibility. Replicated studies on different ethnicities are required to confirm these findings.

Nanobiosensors for detection of opioids: A review of latest advancements.

Opioids are generally used as analgesics in pain treatment. Like many drugs, they have side effects when overdosed and can causeaddiction problems.Illegal drug use and misuse are becoming a major concern for authorities worldwide; thus, it is critical to have precise procedures for detecting them in confiscated samples, biological fluids, and wastewaters. Routine blood and urine tests are insufficient for highly selective determinations and can cause cross-reactivities. For this purpose, nanomaterial-based biosensors are great tools to determine opioid intakes, continuously monitoring the drugs with high sensitivity and selectivity even at very low sample volumes.Nanobiosensors generally comprise a signal transducer nanostructure in which a biological recognition molecule is immobilized onto its surface. Lately, nanobiosensors have been extensively utilized for the molecular detection of opioids. The usage of novel nanomaterials in biosensing has impressed researchers who work on developing biosensors. Nanomaterials with a large surface area have been used to develop nanobiosensors with shorter reaction times and higher sensitivity than conventional biosensors. Colorimetric and fluorescence sensing methods are two kinds of optical sensor systems based on nanomaterials. Noble metal nanoparticles (NPs), such as silver and gold, are the most frequently applied nanomaterials in colorimetric techniques, owing to their unique optical feature of surface plasmon resonance. Despite the progress of an extensive spectrum of nanobiosensors over the last two decades, the future purpose of low-cost, high-throughput, multiplexed clinical diagnostic Lab-on-a-Chip instruments has yet to be fulfilled. In this review, a concise overview of opioids (such as tramadol and buprenorphine, oxycodone and fentanyl, methadone and morphine) is provided as well as information on their classification, mechanism of action, routine tests, and new opioid sensing technologies based on various NPs. In order to highlight the trend of nanostructure development in biosensor applications for opioids, recent literature examples with the nanomaterial type, target molecules, and their limits of detection are discussed.

Breast cancer vaccines: New insights into immunomodulatory and nano-therapeutic approaches.

Breast cancer (BC) is known to be a highly heterogeneous disease that is clinically subdivided into four primary molecular subtypes, each having distinct morphology and clinical implications. These subtypes are principally defined by hormone receptors and other proteins involved (or not involved) in BC development. BC therapeutic vaccines [including peptide-based vaccines, protein-based vaccines, nucleic acid-based vaccines (DNA/RNA vaccines), bacterial/viral-based vaccines, and different immune cell-based vaccines] have emerged as an appealing class of cancer immunotherapeutics when used alone or combined with other immunotherapies. Employing the immune system to eliminate BC cells is a novel therapeutic modality. The benefit of active immunotherapies is that they develop protection against neoplastic tissue and readjust the immune system to an anti-tumor monitoring state. Such immunovaccines have not yet shown effectiveness for BC treatment in clinical trials. In recent years, nanomedicines have opened new windows to increase the effectiveness of vaccinations to treat BC. In this context, some nanoplatforms have been designed to efficiently deliver molecular, cellular, or subcellular vaccines to BC cells, increasing the efficacy and persistence of anti-tumor immunity while minimizing undesirable side effects. Immunostimulatory nano-adjuvants, liposomal-based vaccines, polymeric vaccines, virus-like particles, lipid/calcium/phosphate nanoparticles, chitosan-derived nanostructures, porous silicon microparticles, and selenium nanoparticles are among the newly designed nanostructures that have been used to facilitate antigen internalization and presentation by antigen-presenting cells, increase antigen stability, enhance vaccine antigenicity and remedial effectivity, promote antigen escape from the endosome, improve cytotoxic T lymphocyte responses, and produce humoral immune responses in BC cells. Here, we summarized the existing subtypes of BC and shed light on immunomodulatory and nano-therapeutic strategies for BC vaccination. Finally, we reviewed ongoing clinical trials on BC vaccination and highlighted near-term opportunities for moving forward.