Precision in cancer diagnostics: ultra-sensitive detection of MCF-7 breast cancer cells by gold nanostructure-enhanced electrochemical biosensing.

Timely identification of cancers is pivotal in optimizing treatment efficacy and reducing their widespread impact. This study introduces a novel biosensor for the sensitive electrochemical detection of cancer cells overexpressing mucin 1 (MUC1), a well-established model for breast cancer. The sensor substrate comprises gold columnar nanostructures obtained through glancing angle deposition (GLAD) of copper nanostructures, subsequently replaced by gold via a facile galvanic replacement process. Functionalizing these gold nanostructures with aptamers targeting the MUC1 glycoproteins, a prominent cancer biomarker, enables specific recognition of MCF-7 breast cancer cells. The proposed electrochemical sensing platform offers several advantages, including high selectivity, a wide linear range of detection, a low detection limit of 30 cells per mL, and long-term stability, rendering this sensor highly desirable for definitive breast cancer diagnosis.

Smart co-delivery of plasmid DNA and doxorubicin using MCM-chitosan-PEG polymerization functionalized with MUC-1 aptamer against breast cancer.

This study introduces an innovative co-delivery approach using the MCM-co-polymerized nanosystem, integrating chitosan and polyethylene glycol, and targeted by the MUC-1 aptamer (MCM@CS@PEG-APT). This system enables simultaneous delivery of the GFP plasmid and doxorubicin (DOX). The synthesis of the nanosystem was thoroughly characterized at each step, including FTIR, XRD, BET, DLS, FE-SEM, and HRTEM analyses. The impact of individual polymers (chitosan and PEG) on payload retardation was compared to the co-polymerized MCM@CS@PEG conjugation. Furthermore, the DOX release mechanism was investigated using various kinetic models. The nanosystem's potential for delivering GFP plasmid and DOX separately and simultaneously was assessed through fluorescence microscopy and flow cytometry. The co-polymerized nanosystem exhibited superior payload entrapment (1:100 ratio of Plasmid:NPs) compared to separately polymer-coated counterparts (1:640 ratio of Plasmid:NPs). Besides, the presence of pH-sensitive chitosan creates a smart nanosystem for efficient DOX and GFP plasmid delivery into tumor cells, along with a Higuchi model pattern for drug release. Toxicity assessments against breast tumor cells also indicated reduced off-target effects compared to pure DOX, introducing it as a promising candidate for targeted cancer therapy. Cellular uptake findings demonstrated the nanosystem's ability to deliver GFP plasmid and DOX separately into MCF-7 cells, with rates of 32% and 98%, respectively. Flow cytometry results confirmed efficient co-delivery, with 42.7% of cells showing the presence of both GFP-plasmid and DOX, while 52.2% exclusively contained DOX. Overall, our study explores the co-delivery potential of the MCM@CS@PEG-APT nanosystem in breast cancer therapy. This system's ability to co-deliver multiple agents preciselyopens new avenues for targeted therapeutic strategies.

Coaxial electrospun PGS/PCL and PGS/PGS-PCL nanofibrous membrane containing platelet-rich plasma for skin tissue engineering.

Wound healing will be enhanced using structures with therapeutic effects. This study fabricated a novel nanofibrous scaffold for skin tissue regeneration using a coaxial structure polyglycerol sebacate (PGS)/platelet-rich plasma (PRP) was embedded in the core and two different compositions were selected for the shell; in one group, polycaprolactone (PCL), and in the other group, PGS/PCL blend was used. The physical, mechanical behavior, drug delivery patterns, and cell response of scaffolds were evaluated. Results revealed that by adding PRP to the core and PGS to the shell, fiber diameters decreased to 260.8 ± 31.3 nm. It also decreased the water contact angle from 66° to 32°, that is ideal candidate for cell attachment. The drug release showed a burst release pattern in the first 30 min, followed by a continuous and slow release during the first day. Adding PGS to the shell decreased the elastic modulus, and its value reached about 500 kPa, which is near the skin elastic modulus and will lead to greater mechanical compatibility for cell proliferation. Particularly, the addition of PRP to the fiber structure enhanced the cell viability and cell adhesion with a suitable morphology. Based on the results, nanofibrous PGS-PRP/PGS-PCL dressing can enhance skin tissue regeneration.

The molecular perspective on the melanoma and genome engineering of T-cells in targeting therapy.

Melanoma, an aggressive malignant tumor originating from melanocytes in humans, is on the rise globally, with limited non-surgical treatment options available. Recent advances in understanding the molecular and cellular mechanisms underlying immune escape, tumorigenesis, drug resistance, and cancer metastasis have paved the way for innovative therapeutic strategies. Combination therapy targeting multiple pathways simultaneously has been shown to be promising in treating melanoma, eliciting favorable responses in most melanoma patients. CAR T-cells, engineered to overcome the limitations of human leukocyte antigen (HLA)-dependent tumor cell detection associated with T-cell receptors, offer an alternative approach. By genetically modifying apheresis-collected allogeneic or autologous T-cells to express chimeric antigen receptors, CAR T-cells can appreciate antigens on cell surfaces independently of major histocompatibility complex (MHC), providing a significant cancer cell detection advantage. However, identifying the most effective target antigen is the initial step, as it helps mitigate the risk of toxicity due to "on-target, off-tumor" and establishes a targeted therapeutic strategy. Furthermore, evaluating signaling pathways and critical molecules involved in melanoma pathogenesis remains insufficient. This study emphasizes the novel approaches of CAR T-cell immunoediting and presents new insights into the molecular signaling pathways associated with melanoma.

Advances in nanobased platforms for cardiovascular diseases: Early diagnosis, imaging, treatment, and tissue engineering.

Cardiovascular diseases (CVDs) present a significant threat to health, with traditional therapeutics based treatment being hindered by inefficiencies, limited biological effects, and resistance to conventional drug. Addressing these challenges requires advanced approaches for early disease diagnosis and therapy. Nanotechnology and nanomedicine have emerged as promising avenues for personalized CVD diagnosis and treatment through theranostic agents. Nanoparticles serve as nanodevices or nanocarriers, efficiently transporting drugs to injury sites. These nanocarriers offer the potential for precise drug and gene delivery, overcoming issues like bioavailability and solubility. By attaching specific target molecules to nanoparticle surfaces, controlled drug release to targeted areas becomes feasible. In the field of cardiology, nanoplatforms have gained popularity due to their attributes, such as passive or active targeting of cardiac tissues, enhanced sensitivity and specificity, and easy penetration into heart and artery tissues due to their small size. However, concerns persist about the immunogenicity and cytotoxicity of nanomaterials, necessitating careful consideration. Nanoparticles also hold promise for CVD diagnosis and imaging, enabling straightforward diagnostic procedures and real-time tracking during therapy. Nanotechnology has revolutionized cardiovascular imaging, yielding multimodal and multifunctional vehicles that outperform traditional methods. The paper provides an overview of nanomaterial delivery routes, targeting techniques, and recent advances in treating, diagnosing, and engineering tissues for CVDs. It also discusses the future potential of nanomaterials in CVDs, including theranostics, aiming to enhance cardiovascular treatment in clinical practice. Ultimately, refining nanocarriers and delivery methods has the potential to enhance treatment effectiveness, minimize side effects, and improve patients' well-being and outcomes.

An insight into fluorescence and magnetic resonance bioimaging using a multifunctional polyethyleneimine-passivated gadocarbon dots nanoconstruct assembled with AS1411.

A nanoassembly of PEI-passivated Gd@CDs, a type of aptamer, is presented which was designed and characterized in order to target specific cancer cells based on their recognition of the receptor nucleolin (NCL), which is overexpressed on the cell membrane of breast cancer cells for fluorescence and magnetic resonance imaging and treatment. Using hydrothermal methods, Gd-doped nanostructures were synthesized, then modified by a two-step chemical procedure for subsequent applications: the passivating of Gd@CDs with branched polyethyleneimine (PEI) (to form Gd@CDs-PEI1 and Gd@CDs-PEI2), and using AS1411 aptamer (AS) as a DNA-targeted molecule (to generate AS/Gd@CDs-PEI1 and AS/Gd@CDs-PEI2). Consequently, these nanoassemblies were constructed as a result of electrostatic interactions between cationic Gd@CDs-passivated PEI and AS aptamers, offering efficient multimodal targeting nanoassemblies for cancer cell detection. It has been demonstrated through in vitro studies that both types of AS-conjugated nanoassemblies are highly biocompatible, have high cellular uptake efficiency (equivalent concentration of AS: 0.25 µΜ), and enable targeted fluorescence imaging in nucleolin-positive MCF7 and MDA-MB-231 cancer cells compared to MCF10-A normal cells. Importantly, the as-prepared Gd@CDs, Gd@CDs-PEI1, and Gd@CDs-PEI2 exhibit higher longitudinal relaxivity values (r1) compared with the commercial Gd-DTPA, equal to 5.212, 7.488, and 5.667 mM-1s-1, respectively. Accordingly, it is concluded that the prepared nanoassemblies have the potential to become excellent candidates for cancer targeting and fluorescence/MR imaging agents, which can be applied to cancer imaging and personalized nanomedicine.

Gene network analysis of oxaliplatin-resistant colorectal cancer to target a crucial gene using chitosan/hyaluronic acid/protamine polyplexes containing CRISPR-Cas9.

Colorectal cancer (CRC) treatment is dramatically hampered by resistance to oxaliplatin alone or in the combination of irinotecan or 5-fluorouracil and leucovorin. This study aims to design and assess Chitosan/Hyaluronic Acid/Protamine sulfate (CS/HA/PS) polyplexes loaded with CRISPR plasmid for targeting a key gene in cancer drug resistance. Here, recent findings were considered to validate oxaliplatin-resistant CRC-related genes and systems biology approaches employed to detect the critical gene. The polyplexes were characterized according to particle size, zeta potential, and stability. Moreover, carrier toxicity and transfection efficiency were assessed on oxaliplatin-resistant HT-29 cells. The post-transfection evaluations were performed to confirm gene disruption-mediated CRISPR. Eventually, excision cross complementation group 1(ERCC1), a crucial member of the nucleotide excision repair pathway, was selected to be targeted using CRISPR/Cas9 to reverse oxaliplatin resistance in HT-29 cells. CS/HA/PS polyplexes containing CRISPR/Cas9 plasmid exhibited negligible toxicity and comparable transfection efficiency with Lipofectamine™. Following the efficient gene delivery, sequences in CRISPR/Cas9 target sites were altered, ERCC1 was downregulated, and drug sensitivity was successfully restored in oxaliplatin-resistant cells. Findings indicate that CS/HA/PS/CRISPR polyplexes provide a potential strategy for delivering cargo and targeting oxaliplatin resistance-related gene to manipulate drug resistance as a rising concern in cancer therapeutic approaches.

A comprehensive review on novel targeted therapy methods and nanotechnology-based gene delivery systems in melanoma.

Melanoma, a malignant form of skin cancer, has been swiftly increasing in recent years. Although there have been significant advancements in clinical treatment underlying a well-understanding of melanoma-susceptible genes and the molecular basis of melanoma pathogenesis, the permanency of response to therapy is frequently constrained by the emergence of acquired resistance and systemic toxicity. Conventional therapies, including surgical resection, chemotherapy, radiotherapy, and immunotherapy, have already been used to treat melanoma and are dependent on the cancer stage. Nevertheless, ineffective side effects and the heterogeneity of tumors pose major obstacles to the therapeutic treatment of malignant melanoma through such strategies. In light of this, advanced therapies including nucleic acid therapies (ncRNA, aptamers), suicide gene therapies, and gene therapy using tumor suppressor genes, have lately gained immense attention in the field of cancer treatment. Furthermore, nanomedicine and targeted therapy based on gene editing tools have been applied to the treatment of melanoma as potential cancer treatment approaches nowadays. Indeed, nanovectors enable delivery of the therapeutic agents into the tumor sites by passive or active targeting, improving therapeutic efficiency and minimizing adverse effects. Accordingly, in this review, we summarized the recent findings related to novel targeted therapy methods as well as nanotechnology-based gene systems in melanoma. We also discussed current issues along with potential directions for future research, paving the way for the next-generation of melanoma treatments.

Smartphone-assisted lab-in-a-tube device using gold nanocluster-based aptasensor for detection of MUC1-overexpressed tumor cells.

Developing smartphone technology for point-of-care diagnosis is one of the current favorable trends in the field of biosensors. In fact, using smartphones can provide better accessibility and facility for rapid diagnosis of diseases. On the other hand, the detection of circulating tumor cells (CTCs) is one of the recent methods for the early diagnosis of cancer. Here, a new smartphone-assisted lab-in-a-tube device is introduced for the detection of Mucin 1 (MUC1) overexpressed tumor-derived cell lines using gold nanoclusters (GNCs)-based aptasensor. Accordingly, commercial polyurethane (PU) foam was first coated with graphene oxide (GO) to increase its surface area (8.45-fold), and improve its wettability. The surface of the resulting three-dimensional PU-GO (3DPU-GO) platform was then modified by MUC1 aptamer-GNCs to provide the required sensitivity and specificity through a turn "on/off" detection system. The proposed biosensor was first optimized with a spectrophotometer method. Afterward, findings were evaluated based on the red color intensity of the lab-in-a-tube system; and indicated the high ability of the biosensor for detection of MUC1-overexpressed tumor cell lines in the range of 250-20,000 cells mL-1 with a limit of detection of 221 cells mL-1. In addition, the developed biosensor showed a decent selectivity against positive-control cell lines (MCF-7, and HT-29) in comparison to negative-control cell lines (HEK293, and L929). Notably, the results represented good accordance with reference methods including spectroscopy devices. Ultimately, the results of this work bring a new perspective to the field of point-of-care detection and can be considered in future biosensors.

The potential therapeutic impacts of trehalose on cardiovascular diseases as the environmental-influenced disorders: An overview of contemporary findings.

Cardiovascular diseases (CVDs) as environmental-influenced disorders, are a major concern and the leading cause of death worldwide. A range of therapeutic approaches has been proposed, including conventional and novel methods. Natural compounds offer a promising alternative for CVD treatment due to their ability to regulate molecular pathways with minimal adverse effects. Trehalose is natural compound and disaccharide with unique biological functions and cardio-protective properties. The cardio-protective effects of trehalose are generated through its ability to induce autophagy, which is mediated by the transcription factors TFEB and FOXO1. The stimulation of TFEB plays a significant role in regulating autophagy genes and autophagosome formation. Activation of FOXO1 through dephosphorylation of Foxo1 and blocking of p38 mitogen-activated protein kinase (p38 MAPK) also triggers autophagy dramatically. Trehalose has been shown to reduce CVD risk factors, including atherosclerosis, cardiac remodeling after a heart attack, cardiac dysfunction, high blood pressure, and stroke. It also reduces structural abnormalities of mitochondria, cytokine production, vascular inflammation, cardiomyocyte apoptosis, and pyroptosis. This review provides a molecular overview of trehalose's cardioprotective functions, including its mechanisms of autophagy and its potential to improve CVD symptoms based on clinical evidence.

Crosstalk of Transcriptional Regulators of Adaptive Immune System and microRNAs: An Insight into Differentiation and Development.

MicroRNAs (miRNAs), as small regulatory RNA molecules, are involved in gene expression at the post-transcriptional level. Hence, miRNAs contribute to gene regulation of various steps of different cell subsets' differentiation, maturation, and activation. The adaptive immune system arm, which exhibits the most specific immune responses, is also modulated by miRNAs. The generation and maturation of various T-cell subsets concomitant with B-cells is under precise regulation of miRNAs which function directly on the hallmark genes of each cell subset or indirectly through regulation of signaling pathway mediators and/or transcription factors involved in this maturation journey. In this review, we first discussed the origination process of common lymphocyte progenitors from hematopoietic stem cells, which further differentiate into various T-cell subsets under strict regulation of miRNAs and transcription factors. Subsequently, the differentiation of B-cells from common lymphocyte progenitors in bone marrow and periphery were discussed in association with a network of miRNAs and transcription factors.

Fluorescence anisotropy cytosensing of folate receptor positive tumor cells using 3D polyurethane-GO-foams modified with folic acid: molecular dynamics and in vitro studies.

Integrated polyurethane (PU)-based foams modified with PEGylated graphene oxide and folic acid (PU@GO-PEG-FA) were developed with the goal of capturing and detecting tumor cells with precision. The detection of the modified PU@GO-PEG surface through FA against folate receptor-overexpressed tumor cells is the basis for tumor cell capture. Molecular dynamics (MD) simulations were applied to study the strength of FA interactions with the folate receptor. Based on the obtained results, the folate receptor has intense interactions with FA, which leads to the reduction in the FA interactions with PEG, and so decreases the fluorescence intensity of the biosensor. The synergistic interactions offer the FA-modified foams a high efficiency for capturing the tumor cell. Using a turn-off fluorescence technique based on the complicated interaction of FA-folate receptor generated by target recognition, the enhanced capture tumor cells could be directly read out at excitation-emission wavelengths of 380-450 nm. The working range is between 1×10 2 to 2×10 4 cells mL -1 with a detection limit of 25 cells mL -1 and good reproducibility with relative standard deviation of 2.35%. Overall, findings demonstrate that the fluorescence-based biosensor has a significant advantage for early tumor cell diagnosis.

Clinical characteristics of COVID-19-infected cancer patients, Isfahan, Iran.

Background: Cancer patients, as a highly vulnerable population, are receiving a great deal of attention in the current crisis of coronavirus 2019 (COVID-19). To date, shreds of evidence are not sufficient to the description of COVID-19 outcomes in patients with cancer. This study was performed to evaluate the demographic and clinical characteristics and subsequent outcomes of COVID-19 in cancer patients. Materials and Methods: A hospital-based study was conducted involving 66 cancer patients with a confirmed diagnosis of COVID-19 from January 15, 2020, to December 21, 2020, in Isfahan, Iran. The clinical information was collected by interview and medical records. The statistical analyses were performed to describe categorical variables as well as mean, standard deviation, median, and the interquartile range for quantitative variables. Results: In our study, 66 cancer patients with confirmed COVID-19 (age: 17-97 years; 50% female) were included. Leukemia and bone marrow cancer with a frequency of 25.7% were the most common types of cancer among them. Cancer patients mostly complained of fever, cough and fatigue, and shortness of breath. Among 76.9% of patients discharged from the hospital with relative recovery, 23% died; the most common cause of death was acute respiratory distress syndrome. Age, gender, and type of cancer did not affect cancer mortality. COVID-19 had no potential effect to increase the risk of side effects of anticancer therapies. Conclusion: The results of our studies revealed that cancer is an important risk factor for the higher rate of mortality in patients with COVID-19. These findings could help physicians for the management, treatment, and supportive care of COVID-19 cancer patients.

Association of Clinical Features with Spike Glycoprotein Mutations in Iranian COVID-19 Patients.

BACKGROUND: Mutations in spike glycoprotein, a critical protein of SARS-CoV-2, could directly impact pathogenicity and virulence. The D614G mutation, a non-synonymous mutation at position 614 of the spike glycoprotein, is a predominant variant circulating worldwide. This study investigated the occurrence of mutations in the crucial zone of the spike gene and the association of clinical symptoms with spike mutations in isolated viruses from Iranian patients infected with SARS-CoV-2 during the second and third waves of the COVID-19 epidemic in Isfahan, the third-largest city in Iran. METHODS: The extracted RNA from 60 nasopharyngeal samples of COVID-19 patients were subjected to cDNA synthesis and RT-PCR (in three overlapping fragments). Each patient's reverse transcriptase polymerase chain reaction (RT-PCR) products were assembled and sequenced. Information and clinical features of all sixty patients were collected, summarized, and analyzed using the GENMOD procedure of SAS 9.4. RESULTS: Analysis of 60 assembled sequences identified nine nonsynonymous mutations. The D614G mutation has the highest frequency among the amino acid changes. In our study, in 31 patients (51.66%), D614G mutation was determined. For all the studied symptoms, no significant relationship was observed with the incidence of D614G mutation. CONCLUSIONS: D614G, a common mutation among several of the variants of SARS-CoV-2, had the highest frequency among the studied sequences and its frequency increased significantly in the samples of the third wave compared to the samples of the second wave of the disease.

Three-Dimensional in Vitro Models: A Promising Tool To Scale-Up Breast Cancer Research.

Common models used in breast cancer studies, including two-dimensional (2D) cultures and animal models, do not precisely model all aspects of breast tumors. These models do not well simulate the cell-cell and cell-stromal interactions required for normal tumor growth in the body and lake tumor like microenvironment. Three-dimensional (3D) cell culture models are novel approaches to studying breast cancer. They do not have the restrictions of these conventional models and are able to recapitulate the structural architecture, complexity, and specific function of breast tumors and provide similar in vivo responses to therapeutic regimens. These models can be a link between former traditional 2D culture and in vivo models and are necessary for further studies in cancer. This review attempts to summarize the most common 3D in vitro models used in breast cancer studies, including scaffold-free (spheroid and organoid), scaffold-based, and chip-based models, particularly focused on the basic and translational application of these 3D models in drug screening and the tumor microenvironment in breast cancer.

Graphene oxide quantum dot-chitosan nanotheranostic platform as a pH-responsive carrier for improving curcumin uptake internalization: In vitro & in silico study.

We herein fabricated a cancer nanotheranostics platform based on Graphene Oxide Quantum Dot-Chitosan-polyethylene glycol nanoconjugate (GOQD-CS-PEG), which were targeted with MUC-1 aptamer towards breast and colon tumors. The interaction between aptamer and MUC-1 receptor on the desired cells was investigated utilizing molecular docking. The process of curcumin release was investigated, as well as the potential of the produced nanocomposite in targeted drug delivery, specific detection, and photoluminescence imaging. The fluorescence intensity of GOQD-CS-PEG was reduced due to transferred energy between (cytosine-guanin) base pairs in the hairpin structure of the aptamer, resulting in an "on/off" photoluminescence bio-sensing. Interestingly, the integration of pH-responsive chitosan nanoparticles in the nanocomposite results in a smart nanocomposite capable of delivering more curcumin to desired tumor cells. When selectively binds to the MUC-1 receptor, the two strands of aptamer separate in acidic conditions, resulting in a sustained drug release and photoluminescence recovery. The cytotoxicity results also revealed that the nanocomposite was more toxic to MUC-1-overexpressed tumor cells than to negative control cell lines, confirming its selective targeting. As a result, the proposed nanocomposite could be used as an intelligent cancer nanotheranostic platform for tracing MUC-1-overexpressed tumor cells and targeting them with great efficiency and selectivity.

Gene Editing-Based Technologies for Beta-hemoglobinopathies Treatment.

Beta (ß)-thalassemia is a group of human inherited abnormalities caused by various molecular defects, which involves a decrease or cessation in the balanced synthesis of the ß-globin chains in hemoglobin structure. Traditional treatment for ß-thalassemia major is allogeneic bone marrow transplantation (BMT) from a completely matched donor. The limited number of human leukocyte antigen (HLA)-matched donors, long-term use of immunosuppressive regimen and higher risk of immunological complications have limited the application of this therapeutic approach. Furthermore, despite improvements in transfusion practices and chelation treatment, many lingering challenges have encouraged researchers to develop newer therapeutic strategies such as nanomedicine and gene editing. One of the most powerful arms of genetic manipulation is gene editing tools, including transcription activator-like effector nucleases, zinc-finger nucleases, and clustered regularly interspaced short palindromic repeat-Cas-associated nucleases. These tools have concentrated on γ- or ß-globin addition, regulating the transcription factors involved in expression of endogenous γ-globin such as KLF1, silencing of γ-globin inhibitors including BCL11A, SOX6, and LRF/ZBTB7A, and gene repair strategies. In this review article, we present a systematic overview of the appliances of gene editing tools for ß-thalassemia treatment and paving the way for patients' therapy.

The Importance of SNPs at miRNA Binding Sites as Biomarkers of Gastric and Colorectal Cancers: A Systematic Review.

Dysregulated mRNA-miRNA profiles might have the prospective to be used for early diagnosis of gastrointestinal cancers, estimating survival, and predicting response to treatment. Here, a novel biomarker based on miRNAs binding to mRNAs in single nucleotide polymorphism (SNP) sites related to gastrointestinal cancers is introduced that could act as an early diagnosis. The electronic databases used for the recruiting published articles included EMBASE, SCOPUS, Web of Science, and PubMed, based on MESH keywords and PRISMA methodology. Based on the considered criteria, different experimental articles were reviewed, during which 15 studies with the desired criteria were collected. Accordingly, novel biomarkers in prediction, early prognosis, and diagnosis of gastrointestinal cancers were highlighted. Moreover, it was found that 20 SNP sites and 16 miRNAs were involved in gastrointestinal cancers, with altered expression patterns associated with clinicopathological and demographic data. The results of this systematic study revealed that SNPs could affect the binding of miRNAs in the SNP sites that might play a principal role in the progression, invasion, and susceptibility of gastrointestinal cancers. In addition, it was found that the profiles of SNPs and miRNAs could serve as a convenient approach for the prognosis and diagnosis of gastric and colorectal cancers.

Mesoporous silica@chitosan@gold nanoparticles as "on/off" optical biosensor and pH-sensitive theranostic platform against cancer.

A cancer nanotheranostic system was fabricated based on mesoporous silica@chitosan@gold (MCM@CS@Au) nanosystem targeted by aptamer toward the MUC-1 positive tumor cells. Subsequently, curcumin as an efficient herbal anticancer drug was first encapsulated into chitosan-triphosphate nanoparticles and then the resulted nanoparticle was loaded into the nanosystem (MCM@CS@Au-Apt). The nanosystem successful fabrication was approved at each synthesis step through FTIR, XRD, BET, DLS, FE-SEM, HRTEM, and fluorescence spectroscopy. Besides, the interaction between aptamer and curcumin was evaluated using full atomistic molecular dynamics simulations. The mechanism of curcumin release was likewise investigated through different kinetic models. Afterwards, the potential of the designed nanosystem in targeted imaging, and drug delivery was evaluated using fluorescence microscopy and flow cytometry. It was found that the energy transfer between the base pairs in the hairpin of double strands of DNA aptamer acts as a quencher for MCM@CS@Au fluorescence culminating in an "on/off" optical biosensor. On the other hand, the presence of pH-sensitive chitosan nanoparticles creates smart nanosystem to deliver more curcumin into the desired cells. Indeed, when the aptamer specifically binds to the MUC-1 receptor, its double strands separate under the low pH condition, leading to the drug release and the recovery of the fluorescence ("On" state). Based on the toxicity results, this nanosystem had more toxicity toward the MUC-1-positive tumor cells than MUC-1-negative cells, representing its selective targeting. Therefore, this nanosystem could be introduced as a smart anticancer nanotheranostic system for tracing particular biomarkers (MUC-1), non-invasive fluorescence imaging, and targeted curcumin delivery.

Apolipoprotein B gene mutation related to familial hypercholesterolemia in an Iranian population: With or without hypothyroidism.

BACKGROUND: Familial hypercholesterolemia (FH) leads to elevated low-density lipoprotein cholesterol (LDL-C) levels in plasma. Mutations of its related gene; apolipoprotein B (APOB) is seen in about two percent of the patient with FH. Thyroid disease is usually part of the exclusion criteria for the detection of FH which alters the lipid profile. We evaluated mutations in the APOB gene in patients with high LDL-C levels. MATERIALS AND METHODS: Patients aged between 2 and 80 years with at least one LDL-C level of more than 190 mg/dl were selected (120 patients) from Isfahan Laboratories. Blood samples were obtained from all patients. Genomic DNA was extracted. Primer sequences were designed by Oligo 7.60 to amplify the desired 844 bp region of exon 26 of the APOB gene containing R3500Q and R3500W variants associated with FH. RESULTS: Overall, two patients showed a heterozygous form of a common pathogenic variant in exon 26 named c. 10579 C > T (R3500W, cDNA.10707), and one patient was hypothyroidism. We also recognized another nonpathognomonic variant c. 10913G > A (rs1801701, cDNA.11041) in 13 patients, two of them were hypothyroidism. CONCLUSION: This study for the first time shows the coexistence of APOB mutation in hypothyroidism, which emphasis screening of patients with hypothyroid for FH detection.