Electrochemical biosensors for early diagnosis of glioblastoma.

Glioblastoma (GBM) is a highly aggressive and life-threatening neurological malignancy of predominant astrocyte origin. This type of neoplasm can develop in either the brain or the spine and is also known as glioblastoma multiforme. Although current diagnostic methods such as magnetic resonance imaging (MRI) and positron emission tomography (PET) facilitate tumor location, these approaches are unable to assess disease severity. Furthermore, interpretation of imaging studies requires significant expertise which can have substantial inter-observer variability, thus challenging diagnosis and potentially delaying treatment. In contrast, biosensing systems offer a promising alternative to these traditional approaches. These technologies can continuously monitor specific molecules, providing valuable real-time data on treatment response, and could significantly improve patient outcomes. Among various types of biosensors, electrochemical systems are preferred over other types, as they do not require expensive or complex equipment or procedures and can be made with readily available materials and methods. Moreover, electrochemical biosensors can detect very small amounts of analytes with high accuracy and specificity by using various signal amplification strategies and recognition elements. Considering the advantages of electrochemical biosensors compared to other biosensing methods, we aim to highlight the potential application(s) of these sensors for GBM theranostics. The review's innovative insights are expected to antecede the development of novel biosensors and associated diagnostic platforms, ultimately restructuring GBM detection strategies.

Gene-edited cells: novel allogeneic gene/cell therapy for epidermolysis bullosa.

Epidermolysis bullosa (EB) is a group of rare genetic skin fragility disorders, which are hereditary. These disorders are associated with mutations in at least 16 genes that encode components of the epidermal adhesion complex. Currently, there are no effective treatments for this disorder. All current treatment approaches focus on topical treatments to prevent complications and infections. In recent years, significant progress has been achieved in the treatment of the severe genetic skin blistering condition known as EB through preclinical and clinical advancements. Promising developments have emerged in the areas of protein and cell therapies, such as allogeneic stem cell transplantation; in addition, RNA-based therapies and gene therapy approaches have also become a reality. Stem cells obtained from embryonic or adult tissues, including the skin, are undifferentiated cells with the ability to generate, maintain, and replace fully developed cells and tissues. Recent advancements in preclinical and clinical research have significantly enhanced stem cell therapy, presenting a promising treatment option for various diseases that are not effectively addressed by current medical treatments. Different types of stem cells such as primarily hematopoietic and mesenchymal, obtained from the patient or from a donor, have been utilized to treat severe forms of diseases, each with some beneficial effects. In addition, extensive research has shown that gene transfer methods targeting allogeneic and autologous epidermal stem cells to replace or correct the defective gene are promising. These methods can regenerate and restore the adhesion of primary keratinocytes in EB patients. The long-term treatment of skin lesions in a small number of patients has shown promising results through the transplantation of skin grafts produced from gene-corrected autologous epidermal stem cells. This article attempts to summarize the current situation, potential development prospects, and some of the challenges related to the cell therapy approach for EB treatment.

MicroRNA biosensors for detection of glioblastoma.

Glioblastoma (GBM) is the most common type of malignant brain tumor.The discovery of microRNAs and their unique properties have made them suitable tools as biomarkers for cancer diagnosis, prognosis, and evaluation of therapeutic response using different types of nanomaterials as sensitive and specific biosensors. In this review, we discuss microRNA-based electrochemical biosensing systems and the use of nanoparticles in the evolving development of microRNA-based biosensors in glioblastoma.

MicroRNAs in Male Fertility.

Around 50% of all occurrences of infertility are attributable to the male factor, which is a significant global public health concern. There are numerous circumstances that might interfere with spermatogenesis and cause the body to produce abnormal sperm. While evaluating sperm, the count, the speed at which they migrate, and their appearance are the three primary characteristics that are analyzed. MicroRNAs, also known as miRNAs, are present in all physiological fluids and tissues. They participate in both physiological and pathological processes. Researches have demonstrated that the expression of microRNA genes differs in infertile men. These genes regulate spermatogenesis at various stages and in several male reproductive cells. Hence, microRNAs have the potential to act as useful indicators in the diagnosis and treatment of male infertility and other diseases affecting male reproduction. Despite this, additional research is necessary to determine the precise miRNA regulation mechanisms.

MicroRNA biosensors for the detection of liver cancer.

Liver cancer is one of the deadliest types worldwide and early diagnosis is highly important for successful treatment. Therefore, it is necessary to develop rapid, sensitive, simple, and inexpensive analytical tools for its detection. MicroRNAs (miRNA) represent unique biomarkers whose expression in biofluids is strongly associated with cancer in general and miR-21, -31, -122, -145, -146a, -200c, -221, -222, and -223 in liver cancer, specifically. Various biosensors for miRNA detection have been developed. These include electrochemical biosensors based on amperometric, potentiometric, conductometric and impedimetric technology. Furthermore, the use of advanced nanomaterials with enhanced chemical stability, conductivity and electrocatalytic activity have greatly increased the sensitivity and specificity of these devices. The present review focuses on recent advances in electrochemical biosensors for miRNA detection in liver cancer.

Exosomal long non-coding RNAs in glioblastoma.

Glioblastoma multiforme (GBM) is the most prevalent primary tumor found in the central nervous system, accounting for 70% of all adult brain tumors. The median overall survival rate is one year post-diagnosis with treatment, and only four months without treatment. Current GBM diagnostic methods, such as magnetic resonance imaging (MRI), surgery, and brain biopsies, have limitations. These include difficulty distinguishing between tumor recurrence and post-surgical necrotic regions, and operative risks associated with obtaining histological samples through direct surgery or biopsies. Consequently, there is a need for rapid, inexpensive, and minimally invasive techniques for early diagnosis and improved subsequent treatment. Research has shown that tumor-derived exosomes containing various long non-coding RNAs (lncRNAs) play critical regulatory roles in immunomodulation, cancer metastasis, cancer development, and drug resistance in GBM. They regulate genes that enhance cancer growth and progression and alter the expression of several key signaling pathways. Due to the specificity and sensitivity of exosomal lncRNAs, they have the potential to be used as biomarkers for early diagnosis and prognosis, as well as to monitor a patient's response to chemotherapy for GBM. In this review, we discuss the role of exosomal lncRNAs in the pathogenesis of GBM and their potential clinical applications for early diagnosis.

MicroRNA biosensors in lung cancer.

Lung cancer has been one of the leading causes of death over the past century. Unfortunately, the reliance on conventional methods to diagnose the phenotypic properties of tumors hinders early-stage cancer diagnosis. However, recent advancements in identifying disease-specific nucleotide biomarkers, particularly microRNAs, have brought us closer to early-stage detection. The roles of miR-155, miR-197, and miR-182 have been established in stage I lung cancer. Recent progress in synthesizing nanomaterials with higher conductivity has enhanced the diagnostic sensitivity of electrochemical biosensors, which can detect low concentrations of targeted biomarkers. Therefore, this review article focuses on exploring electrochemical biosensors based on microRNA in lung cancer.

Evaluating the incidence of ampC-ß-lactamase genes, biofilm formation, and antibiotic resistance among hypervirulent and classical Klebsiella pneumoniae strains.

AIM: Both immunocompetent and healthy individuals can become life-threateningly ill when exposed to the hypervirulent (hvKp) strains of Klebsiella pneumoniae (Kp). The main objectives of this study were to evaluate the presence of ampC-lactamase genes, biofilm formation, and antibiotic resistance in clinical strains of hvKp and cKp (classical K. pneumoniae). MATERIALS AND METHODS: Kp strains were collected from patients referred to Shahidzadeh Hospital in Behbahan City, Khuzestan Province, Iran. Several techniques were used to identify hvKp. The hypermucoviscosity phenotype was determined using the string test. Isolates that developed dark colonies on tellurite agar were assumed to be hvKp strains. If any of the iucA, iutA, or peg-344 genes were detected, the isolates were classified as hvKp. Phenotypic and genotypic detection of AmpC ß-lactamases of hvKp strains was performed by the combined disk method and polymerase chain reaction, respectively. In addition, crystal violet staining was used to determine the biofilm formation of these isolates. RESULTS: For this study, 76 non-duplicative isolates of Kp were collected. Overall, 22 (28.94%) strains had positive string test results, and 31 (40.78%) isolates were grown in tellurite-containing medium. The genes iucA and iutA or peg-344 were found in 23.68% of all Kp strains and in 50% of tellurite-resistant isolates, respectively. The most effective antibiotics against hvKp isolates were tetracycline (85.52%) and chloramphenicol (63.15%). Using the cefoxitin disc diffusion method, we observed that 56.57% (43/76) of the strains were AmpC producer. A total of 30.26% (n = 23/76) of the isolates tested positive for at least one ampC gene, including blaDHA (52.63%, n = 40), blaCIT (40.78%, n = 31), blaACC (19.76%, n = 15), blaMOX (25%, n = 19), and blaFOX (43.42%, n = 33). Biofilm formation analysis revealed that most hvKp isolates were weak (n = 6, 40%) and moderate (n = 5, 33.33%) biofilm producers. CONCLUSION: Healthcare practitioners should consider the possibility of the existence and acquisition of hvKp everywhere. The exact mechanisms of bacterial acquisition are also unknown, and it is unclear whether the occurrence of infections is related to healthcare or not. Thus, there are still many questions about hvKp that need to be investigated.

Nano-delivery systems as a promising therapeutic potential for epilepsy: Current status and future perspectives.

Epilepsy is a common chronic neurological disorder caused by aberrant neuronal electrical activity. Antiseizure medications (ASMs) are the first line of treatment for people with epilepsy (PWE). However, their effectiveness may be limited by their inability to cross the blood-brain barrier (BBB), among many other potential underpinnings for drug resistance in epilepsy. Therefore, there is a need to overcome this issue and, hopefully, improve the effectiveness of ASMs. Recently, synthetic nanoparticle-based drug delivery systems have received attention for improving the effectiveness of ASMs due to their ability to cross the BBB. Furthermore, exosomes have emerged as a promising generation of drug delivery systems because of their potential benefits over synthetic nanoparticles. In this narrative review, we focus on various synthetic nanoparticles that have been studied to deliver ASMs. Furthermore, the benefits and limitations of each nano-delivery system have been discussed. Finally, we discuss exosomes as potentially promising delivery tools for treating epilepsy.

MicroRNA electrochemical biosensors for pancreatic cancer.

Pancreatic cancer (PC) is one of the deadliest cancers worldwide. MicroRNAs (miRs) are sensitive molecular diagnostic tools that can serve as highly accurate biomarkers in many disease states in general and cancer specifically. MiR-based electrochemical biosensors can be easily and inexpensively manufactured, making them suitable for clinical use and mass production for point-of-care use. This paper reviews nanomaterial-enhanced miR-based electrochemical biosensors in pancreatic cancer detection, analyzing both labeled and label-free approaches, as well as enzyme-based and enzyme-free methods.

Liposomal delivery system/adjuvant for tuberculosis vaccine.

As reported by the World Health Organization, about 10 million individuals were infected with tuberculosis (TB) worldwide. Moreover, approximately 1.5 million people died of TB, of which 214,000 were infected with HIV simultaneously. Due to the high infection rate, the need for effective TB vaccination is highly felt. Until now, various methodologies have been proposed for the development of a protein subunit vaccine for TB. These vaccines have shown higher protection than other vaccines, particularly the Bacillus culture vaccine. The delivery system and safety regulator are common characteristics of effective adjuvants in TB vaccines and the clinical trial stage. The present study investigates the current state of TB adjuvant research focusing on the liposomal adjuvant system. Based on our findings, the liposomal system is a safe and efficient adjuvant from nanosize to microsize for vaccinations against TB, other intracellular infections, and malignancies. Clinical studies can provide valuable feedback for developing novel TB adjuvants, which ultimately enhance the impact of adjuvants on next-generation TB vaccines.

Exosomes: Promising Delivery Tools for Overcoming Blood-Brain Barrier and Glioblastoma Therapy.

Gliomas make up virtually 80% of all lethal primary brain tumors and are categorized based on their cell of origin. Glioblastoma is an astrocytic tumor that has an inferior prognosis despite the ongoing advances in treatment modalities. One of the main reasons for this shortcoming is the presence of the blood-brain barrier and blood-brain tumor barrier. Novel invasive and non-invasive drug delivery strategies for glioblastoma have been developed to overcome both the intact blood-brain barrier and leverage the disrupted nature of the blood-brain tumor barrier to target cancer cells after resection-the first treatment stage of glioblastoma. Exosomes are among non-invasive drug delivery methods and have emerged as a natural drug delivery vehicle with high biological barrier penetrability. There are various exosome isolation methods from different origins, and the intended use of the exosomes and starting materials defines the choice of isolation technique. In the present review, we have given an overview of the structure of the blood-brain barrier and its disruption in glioblastoma. This review provided a comprehensive insight into novel passive and active drug delivery techniques to overcome the blood-brain barrier, emphasizing exosomes as an excellent emerging drug, gene, and effective molecule delivery vehicle used in glioblastoma therapy.

MicroRNA biosensors for detection of gastrointestinal cancer.

Gastrointestinal (GI) cancers are one of the most common causes of cancer-related mortality. The discovery of microRNAs (miRs) and their unique role in cancer and other diseases has prompted the development of highly sensitive molecular diagnostic tools using nanomaterials as sensitive and specific biosensors. Among these, electrochemical biosensors, which are based on a simple and inexpensive design, make them desirable in clinical applications as well as a mass-produced point-of-care device. We review miR-based electrochemical biosensors in GI cancer and examine the use of nanoparticles in the evolving development of miR-based biosensors. Among these, a number of approaches including redox labeled probes, catalysts, redox intercalating agents and free redox indicators are highlighted for use in electrochemical biosensor technology.

Exosomal lncRNAs in gastrointestinal cancer.

Gastrointestinal cancer (GIC) remains a leading cause of morbidity and mortality worldwide. Unfortunately, these cancers are diagnosed in advanced metastatic stages due to lack of reliable biomarkers that are sufficiently specific and sensitive in early disease. There has been growing evidence that circulating exosomes can be used to diagnose cancer non-invasively with limited risks and side effects. Furthermore, exosomal long non-coding RNAs (lncRNAs) are emerging as a new class of promising biomarkers in cancer. This review provides an overview of the extraction and detection of exosomal lncRNAs with a focus on their potential role in GIC.

A review of highly sensitive electrochemical genosensors for microRNA detection: A novel diagnostic platform for neurodegenerative diseases diagnostics.

The significant role of microRNAs in regulating gene expression and in disease tracking has handed the possibility of robust and accurate diagnosis of various diseases. Measurement of these biomarkers has also had a significant impact on the preparation of natural samples. Discovery of miRNAs is a major challenge due to their small size in the real sample and their short length, which is generally measured by complex and expensive methods. Electrochemical nanobiosensors have made significant progress in this field. Due to the delicate nature of nerve tissue repair and the significance of rapid-fire feature of neurodegenerative conditions, these biosensors can be reliably promising. This review presents advances in the field of neurodegenerative diseases diagnostics. At the same time, there are still numerous openings in this field that are a bright prospect for researchers in the rapid-fire opinion of neurological diseases and indeed nerve tissue repair.

Recent insights into the roles of circular RNAs in human brain development and neurologic diseases.

Circular RNAs (circRNAs) are a novel class of non-coding RNAs. They are single-stranded RNA transcripts characterized with a closed loop structure making them resistant to degrading enzymes. Recently, circRNAs have been suggested with regulatory roles in gene expression involved in controlling various biological processes. Notably, they have demonstrated abundance, dynamic expression, back-splicing events, and spatiotemporally regulation in the human brain. Accordingly, they are expected to be involved in brain functions and related diseases. Studies in animals and human brain have revealed differential expression of circRNAs in brain compartments. Interestingly, contributing roles of circRNAs in the regulation of central nervous system (CNS) development have been demonstrated in a number of studies. It has been proposed that circRNAs play role in substantial neurological functions like neurotransmitter-associated tasks, neural cells maturation, and functions of synapses. Furthermore, 3 main pathways have been identified in association with circRNAs's host genes including axon guidance, Wnt signaling, and transforming growth factor beta (TGF-ß) signaling pathways, which are known to be involved in substantial functions like migration and differentiation of neurons and specification of axons, and thus play role in brain development. In this review, we have an overview to the biogenesis, biological functions of circRNAs, and particularly their roles in human brain development and the pathogenesis of neurodegenerative diseases including Alzheimer's diseases, multiple sclerosis, Parkinson's disease and brain tumors.

Review of electrochemical and optical biosensors for testosterone measurement.

Testosterone is an anabolic steroid and a major sex hormone in males. It plays vital roles, including developing the testis, penis, and prostate, increasing muscle and bone, and sperm production. In both men and women, testosterone levels should be in normal ranges. Besides, testosterone and its analogs are major global contributors to doping in sport. Due to the importance of testosterone testing, novel, accurate biosensors have been developed. This review summarizes the various methods for testosterone measurement. Also, recent optical and electrochemical approaches for the detection of testosterone and its analogs have been discussed.

Non-coding RNAs in gynecologic cancer.

The term "gynecologic cancer" pertains to neoplasms impacting the reproductive tissues and organs of women encompassing the endometrium, vagina, cervix, uterus, vulva, and ovaries. The progression of gynecologic cancer is linked to various molecular mechanisms. Historically, cancer research primarily focused on protein-coding genes. However, recent years have unveiled the involvement of non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs (LncRNAs), and circular RNAs, in modulating cellular functions within gynecological cancer. Substantial evidence suggests that ncRNAs may wield a dual role in gynecological cancer, acting as either oncogenic or tumor-suppressive agents. Numerous clinical trials are presently investigating the roles of ncRNAs as biomarkers and therapeutic agents. These endeavors may introduce a fresh perspective on the diagnosis and treatment of gynecological cancer. In this overview, we highlight some of the ncRNAs associated with gynecological cancers.

Designing a humanized immunotoxin based on DELTA-stichotoxin-Hmg2a toxin: an in silico study.

Breast cancer remains the most frequently diagnosed cancer and the principal cause of mortality by malignancy in women. HER2 positive subtype includes 15-20% of breast cancer cases. This receptor could be an appropriate mark for targeting breast cancer cells. Immunotherapy methods compared to current cancer treatment methods have the lowest side effects. DELTA-stichotoxin-Hmg2a is isolated from the sea anemone and kills cells through pore formation. In the current study, we designed and evaluated an immunotoxin composed of pertuzumab and DELTA-stichotoxin-Hmg2a-derived scFv by bioinformatics tools. The designed immunotoxin was constructed using the amino acid sequences. Then, secondary structure and physico-chemical features were studied, and the tertiary structure of the immunotoxin was built according to the homology modeling methods. The validation and allergenicity of the model were assessed. The immunotoxin and receptor were docked and molecular dynamics simulation indicated the construct stability. The analysis results indicated that the construct is a stable protein that could have a natural-like structure and would not be an allergen, so this immunotoxin could effectively target HER2 receptors. Therefore, our designed immunotoxin could be an appropriate immunotoxin against HER2-positive breast cancer and could be a challenging topic for future in vitro and in vivo studies.

Exosomal noncoding RNAs in prostate cancer.

Prostate cancer (PCa) is the second most common cancer and the fifth leading cause of mortality among men. The recurrent reports of false-positive results of common PCa biomarkers have led to the introduction of some promising biomarkers for PCa, such as exosomal non-coding RNAs (ncRNAs). Exosomes contain various components, such as several ncRNAs (miRNAs and lncRNAs), which are important in the initiation and progression of PCa. These ncRNAs also reflect the state of the origin cell. In this article, we reviewed research on the importance and roles of ncRNAs in PCa, focusing on exosomal ncRNAs. We highlighted plasma exosomal miRNAs (8 miRNAs), urine exosomal miRNAs (19miRNAs), serum miRNAs (2 miRNAs), and five miRNAs in semen used for PCa diagnosis. Also, four exosomal lncRNAs in plasma and urine can be used as biomarkers for PCa diagnosis.