Role of Non-coding RNAs in the Response of Glioblastoma to Temozolomide.

Chemotherapy and radiotherapy are widely used in clinical practice across the globe as cancer treatments. Intrinsic or acquired chemoresistance poses a significant problem for medical practitioners and researchers, causing tumor recurrence and metastasis. The most dangerous kind of malignant brain tumor is called glioblastoma multiforme (GBM) that often recurs following surgery. The most often used medication for treating GBM is temozolomide chemotherapy; however, most patients eventually become resistant. Researchers are studying preclinical models that accurately reflect human disease and can be used to speed up drug development to overcome chemoresistance in GBM. Non-coding RNAs (ncRNAs) have been shown to be substantial in regulating tumor development and facilitating treatment resistance in several cancers, such as GBM. In this work, we mentioned the mechanisms of how different ncRNAs (microRNAs, long non-coding RNAs, circular RNAs) can regulate temozolomide chemosensitivity in GBM. We also address the role of these ncRNAs encapsulated inside secreted exosomes.

The role of IL-2 cytokine family in asthma.

BACKGROUND: The interleukin-2 (IL-2) family of cytokines, including IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21, are pivotal regulators of the immune response, impacting both innate and adaptive immunity. Understanding their molecular characteristics, receptor interactions, and signalling pathways is essential for elucidating their roles in health and disease. OBJECTIVES: This review provides a comprehensive overview of the IL-2 family of cytokines, highlighting their molecular biology, receptor interactions, and signalling mechanisms. Furthermore, it explores the involvement of IL-2 family cytokines in the pathogenesis of chronic respiratory diseases, with a specific focus on chronic obstructive pulmonary disease (COPD) and asthma. METHODS: A thorough literature review was conducted to gather insights into the molecular biology, receptor interactions, and signalling pathways of IL-2 family cytokines. Additionally, studies investigating the roles of these cytokines in chronic respiratory diseases, particularly COPD and asthma, were analysed to discern their implications in wider pathophysiology of disease. RESULTS: IL-2 family cytokines exert pleiotropic effects on immune cells, modulating cellular proliferation, differentiation, and survival. Dysregulation of IL-2 family cytokines has been implicated in the pathogenesis of chronic respiratory illnesses, including COPD and asthma. Elevated levels of IL-2 and IL-9 have been associated with disease severity in COPD, while IL-4 and IL-9 play crucial roles in asthma pathogenesis by promoting airway inflammation and remodelling. CONCLUSION: Understanding the intricate roles of IL-2 family cytokines in chronic respiratory diseases provides valuable insights into potential therapeutic targets for these conditions. Targeting specific cytokines or their receptors may offer novel treatment modalities to attenuate disease progression and improve clinical outcomes in patients with COPD and asthma.

Circular RNAs: a small piece in the heart failure puzzle.

Cardiovascular disease, specifically heart failure (HF), remains a significant concern in the realm of healthcare, necessitating the development of new treatments and biomarkers. The RNA family consists of various subgroups, including microRNAs, PIWI-interacting RNAs (piRAN) and long non-coding RNAs, which have shown potential in advancing personalized healthcare for HF patients. Recent research suggests that circular RNAs, a lesser-known subgroup of RNAs, may offer a novel set of targets and biomarkers for HF. This review will discuss the biogenesis of circular RNAs, their unique characteristics relevant to HF, their role in heart function, and their potential use as biomarkers in the bloodstream. Furthermore, future research directions in this field will be outlined. The stability of exosomal circRNAs makes them suitable as biomarkers, pathogenic regulators, and potential treatments for cardiovascular diseases such as atherosclerosis, acute coronary syndrome, ischemia/reperfusion injury, HF, and peripheral artery disease. Herein, we summarized the role of circular RNAs and their exosomal forms in HF diseases.

Umbilical cord mesenchymal stem cells and lung cancer: We should be hopeful or hopeless?

Lung cancer (LC) is one of the leading causes of cancer-caused death that possesses a poor prognosis and low survival rate worldwide. In general, LC is classified into small-cell (SCLC) and non-small-cell carcinoma (NSCLC) (involving 80% of patients). Although chemotherapy, radiotherapy, surgery, and molecular-targeted therapy are considered standard approaches for LC treatment, these options have low success with detrimental effects on the life quality of patients. Ergo, recommending treatment with maximum effectiveness and minimum side effects for LC patients has been a substantial challenge for researchers and clinicians in the present era. Recently, mesenchymal stem cells (MSCs)-based strategies have sparked much interest in preventing or treating numerous illnesses. These multipotent stem cells can be isolated from diverse sources, such as umbilical cord, bone marrow, and adipose tissue. Among these sources, umbilical cord mesenchymal stem cells (UC-MSCs) have been in the spotlight of MSCs-based therapies thanks to their considerable advantages, such as high proliferation ability, low immune reactions and tumorigenesis, and easiness in collection and isolation. Some experimental studies have investigated the functionality of intact UC-MSCs and extracellular vesicles, exosomes, and conditioned medium derived from UC-MSCs, as well as genetically engineered UC-MSCs. In this review, we aimed to highlight the influences of these UMSCs-based methods in LC treatment with cellular and molecular insights.

Royal jelly and its hormonal effects in breast cancer: a literature review.

BACKGROUND: Breast cancer is the most common cancer in women which can be cured in most individuals with early-stage non-metastatic disease. Imbalance in estrogen signaling pathways and propagating levels of estrogens has important roles in breast cancer development. Targeting the estrogen receptor signaling pathway is linked to breast cancer treatment. Royal jelly is one of the bee products containing 10-hydroxy-2-decenoic acid, a structure similar to mammalian estrogen, allowing it to attach to estrogen receptors. It is considered as a general tonic and immunomodulator which may be helpful in reducing the side effects of cancer treatments. Currently, there are controversial data regarding the pros and cons of royal jelly in cancer. Here we provide an overview of the effects of royal jelly on sex hormones and its possible role in breast cancer. METHODS: Electronic databases including PubMed, Scopus, and Web of Science were searched with the search terms royal jelly, cancer, and sexual hormones. All preclinical and clinical studies regarding the hormonal effects of royal jelly were included. RESULTS: According to the collected preclinical data, consumption of royal jelly at daily doses below 200 mg/kg can be useful to decrease the risk of breast cancer since it reduces the serum level of estrogen; whereas increases progesterone, which subsequently decreases the expression of ERs on the ER-positive cells. CONCLUSION: Future clinical studies are essential to confirm the safe dose of royal jelly as an adjuvant therapy in breast cancer.

RNA therapeutics for kidney injury.

RNA therapy involves utilizing RNA-based molecules to control biological pathways, aiming to cure specific diseases. As our understanding of RNA functions and their roles has expanded, the application of RNA therapies has broadened to target various therapeutic points. This approach holds promise for treating a range of diseases, including kidney diseases. Therapeutic RNA can be employed to target specific genes or pathways implicated in the development of kidney conditions, such as inflammation, fibrosis, and oxidative stress. This review highlights the therapeutic potential of RNA-based therapies across different types of kidney diseases, encompassing infection, inflammation, nephrotoxicity, and ischemia/reperfusion injury. Furthermore, studies have pinpointed the specific kidney cells involved in RNA therapy. To address challenges hindering the potential impact of RNA-based drugs on their targets, nanotechnology is integrated, and RNA-loaded vehicles with ligands are explored for more efficient outcomes.

Types of RNA therapeutics.

RNA therapy is one of the new treatments using small RNA molecules to target and regulate gene expression. It involves the application of synthetic or modified RNA molecules to inhibit the expression of disease-causing genes specifically. In other words, it silences genes and suppresses the transcription process. The main theory behind RNA therapy is that RNA molecules can prevent the translation into proteins by binding to specific messenger RNA (mRNA) molecules. By targeting disease-related mRNA molecules, RNA therapy can effectively silence or reduce the development of harmful proteins. There are different types of RNA molecules used in therapy, including small interfering RNAs (siRNAs), microRNAs (miRNAs), aptamer, ribozyme, and antisense oligonucleotides (ASOs). These molecules are designed to complement specific mRNA sequences, allowing them to bind and degrade the targeted mRNA or prevent its translation into protein. Nanotechnology is also highlighted to increase the efficacy of RNA-based drugs. In this chapter, while examining various methods of RNA therapy, we discuss the advantages and challenges of each.

Phytostilbenes in lymphoma: Focuses on the mechanistic and clinical prospects of resveratrol, pterostilbene, piceatannol, and pinosylvin.

Lymphoma is a cancer affecting the lymphatic system that fights infections and diseases. In addition to surgery, radiotherapy, and chemotherapy, novel approaches have recently been investigated, such as phytostilbenes in treating lymphoma. Phytostilbenes are natural compounds present in various plants and have been shown to have different therapeutic effects, including anticancer properties. Resveratrol is a main phytostilbene with various derivates followed by pterostilbene and piceatannol. Studies have revealed that phytostilbenes can suppress the growth and proliferation of lymphoma cells by inducing apoptosis and inhibiting specific enzyme activity in cancer cell survival. The compounds also have antiinflammatory effects contributing to reducing lymphoma-associated inflammation. Additionally, phytostilbenes have been shown to increase the immune system's ability to fight cancer cells by activating immune cells (T-cells and natural killer cells). This review investigates the potential therapeutic effects of phytostilbenes, including resveratrol, pterostilbene, piceatannol, and pinosylvin, against lymphoma.

In vitro and in vivo studies of Dragon's blood plant (D. cinnabari)-loaded electrospun chitosan/PCL nanofibers: Cytotoxicity, antibacterial, and wound healing activities.

The D. cinnabari plant was loaded into the chitosan (Chn)/polycaprolactone (PCL) nanofibers in two forms: resin (D. cinnabari) and its ethyl acetate fraction. The Chn/PCL, Chn/PCL/D. cinnabari (CPD, 1, 3, and 5 %), and Chn/PCL/ethyl acetate extract D. cinnabari (CPED, 1, 3, and 5 %) showed no toxicity against human dermal fibroblast cells. The lactate dehydrogenase assay results indicated that the toxicity of pour, coated D. cinnabari, and CPED nanofibers were lower than 10 and 15 % after 1 and 3 days, respectively. The antibacterial results showed the inhibition zone for ethyl acetate extract D. cinnabari (ED-3 %), the Chn/PCL-2, and CPED3% nanofibers was 8.1, 7.4, 4.2, 5.1 mm, 12.8, 12.4, 21.7, 17.2 mm, and 24.7, 22.9, 37.1, 30.2 mm against S. aureus, B. subtilis, E. coli, and P. aeruginosa, respectively. The antibacterial activity results showed synergistic effect between the Chn/PCL and ethyl acetate extract D. cinnabari occurred. The diameter of wounds (1.50 × 1.50 cm diameter) made on the dorsal surface of rabbits reduced to 1.50 × 0.70, 0.50 × 0.30, 1.00 × 1.00, 0.60 × 0.50, 0.20 × 0.05, and 0.00 × 0.00 cm in the presence of ordinary gauze dressing, silver sulfadiazine, ED-3 %, Chn/PCL-2, CPD3%, and CPED3%nanofibers, respectively, after 14 days.

Mesenchymal stem cells and ovarian cancer: Is there promising news?

Ovarian cancer (OC) is described as a heterogeneous complex condition with high mortality, weak prognosis, and late-stage presentation. OC has several subgroups based on different indices, like the origin and histopathology. The current treatments against OC include surgery followed by chemotherapy and radiotherapy; however, these methods have represented diverse side effects without enough effectiveness on OC. Recently, mesenchymal stem cell (MSC)-based therapy has acquired particular attention for treating diverse problems, such as cancer. These multipotent stem cells can be obtained from different sources, such as the umbilical cord, adipose tissues, bone marrow, and placenta, and their efficacy has been investigated against OC. Hence, in this narrative review, we aimed to review and discuss the present studies about the effects of various sources of MSCs on OC with a special focus on involved mechanisms.

Long non-coding RNAs and female infertility: What do we know?

Ten percent of people who are of reproductive age experience infertility. Sometimes the most effective therapies, including technology for assisted reproduction, may lead to unsuccessful implantation. Because of the anticipated epigenetic alterations of in vitro as well as in vitro fertilization growth of embryos, these fertility techniques have also been linked to unfavorable pregnancy outcomes linked to infertility. In this regard, a variety of non-coding RNAs such as long noncoding RNAs (lncRNAs) act as epigenetic regulators in the various physiological and pathophysiological events such as infertility. LncRNAs have been made up of cytoplasmic and nuclear nucleotides; RNA polymerase II transcribes these, which are lengthier than 200 nt. LncRNAs perform critical roles in a number of biological procedures like nuclear transport, X chromosome inactivation, apoptosis, stem cell pluripotency, as well as genomic imprinting. A significant amount of lncRNAs were linked into a variety of biological procedures as high throughput sequencing technology advances, including the development of the testes, preserving spermatogonial stem cells' capacity for differentiation along with self-renewal, and controlling spermatocyte meiosis. All of them point to possible utility of lncRNAs to be biomarkers and treatment aims for female infertility. Herein, we summarize various lncRNAs that are involved in female infertility.

Evaluation of expression pattern of cellular miRNAs (let-7b, miR-29a, miR-126, miR-34a, miR-181a-5p) and IL-6, TNF-α, and TGF-ß in patients with pseudoexfoliation syndrome.

Pseudoexfoliation syndrome (PEX) is a critical clinical and biological extracellular matrix systemic disorder. Despite the unknown nature of PEX etiopathogenesis, it is proven to be associated with various genes and factors. The present research focused on analyzing the expression of miR and inflammatory cytokines in PEX. Serum and aqueous humor (AH) were collected prior to cataract surgery or trabeculectomy from 99 participants (64 with PEX glaucoma, and 35 controls). Real-time PCR was used for assessing the expression pattern of some miRNAs namely let-7b, miR-29a, miR-126, miR-34a, and miR-181a-5p. ELISA was carried out to explore the transcription of some inflammatory cytokines such as TGF-ß, TNF-α, and IL-6. The indication of our results was a significant enhancement in the expression of let-7, miR-34a, and miR-181a-5p in PEX in contrast to the control group. Notwithstanding a significant suppression in miR-29a, and miR-126 expression levels in PEX in contrast to the control group. Analysis of ROC curve revealed that miR-29a and miR-34a are able to act as useful markers in order to discriminate the PEX group from the PEX negative subjects which were determined as the control group. According to the results obtained, the mean levels of TGF-ß, TNF-α, and IL-6 upregulated among PEX subjects in contrast to control samples. In conclusion, our findings indicated that the selected cytokines alongside the selected miRNAs could be introduced as a biomarker panel in the diagnosis of PEX.

Human umbilical cord mesenchymal stem cells: Heralding an effective treatment against esophageal cancer?

Esophageal cancer (EC), as one of the leading causes of cancer-associated mortality, influences a remarkable population of subjects globally and is histologically divided into two types, comprising esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). Although several therapeutic approaches are present for EC, such as radiotherapy, chemotherapy, and surgery, these options have low success with serious side effects, for example, gastrointestinal toxicity, esophagitis, and pulmonary complications. Thus, utilizing an effective tool with low side effects is urgent. Newly, mesenchymal stem cells (MSCs) have received special interest for treating diverse diseases, such as cancer. Among different sources of MSCs, human umbilical cord MSCs have notable benefits, and reports expressed that they may be effective in EC treatment. For this purpose, in this review study, we aimed to summarize evidence regarding the effects of human umbilical cord MSCs on EC with a mechanistic insight.

Immunomodulatory Therapeutic Effects of Curcumin on M1/M2 Macrophage Polarization in Inflammatory Diseases.

BACKGROUND: Due to their plasticity, macrophages exert critical effects on both promoting and suppressing inflammatory processes. Pathologic inflammatory conditions are frequently correlated with dynamic alterations in macrophage activation, with classically activated M1 cells associated with the promotion and maintenance of inflammation and M2 cells being linked to the resolution or smouldering of chronic inflammation. Inflammation deputes a common feature of various chronic diseases and the direct involvement in the insurgence and development of these conditions. Macrophages participate in an autoregulatory loop characterizing the inflammatory process, as they produce a wide range of biologically active mediators that exert either deleterious or beneficial effects during the inflammation. Therefore, balancing the favorable ratios of M1/M2 macrophages can help ameliorate the inflammatory landscape of pathologic conditions. Curcumin is a component of turmeric with many pharmacological properties. OBJECTIVE: Recent results from both in-vivo and in-vitro studies have indicated that curcumin can affect polarization and/or functions of macrophage subsets in the context of inflammation-related diseases. There is no comprehensive review of the impact of curcumin on cytokines involved in macrophage polarization in the context of inflammatory diseases. The present review will cover some efforts to explore the underlying molecular mechanisms by which curcumin modulates the macrophage polarization in distant pathological inflammatory conditions, such as cancer, autoimmunity, renal inflammation, stroke, atherosclerosis, and macrophage-driven pathogenesis. RESULTS: The accumulation of the findings from in vitro and in vivo experimental studies suggests that curcumin beneficially influences M1 and M2 macrophages in a variety of inflammatory diseases with unfavorable macrophage activation. CONCLUSION: Curcumin not only enhances anti-tumor immunity (via shifting M polarization towards M1 phenotype and/or up-regulation of M1 markers expression) but ameliorates inflammatory diseases, including autoimmune diseases (experimental autoimmune myocarditis and Behcet's disease), nephropathy, chronic serum sickness, stroke, and atherosclerosis.

Chimeric antigen receptor T (CAR-T) cells: Novel cell therapy for hematological malignancies.

Over the last decade, the emergence of several novel therapeutic approaches has changed the therapeutic perspective of human malignancies. Adoptive immunotherapy through chimeric antigen receptor T cell (CAR-T), which includes the engineering of T cells to recognize tumor-specific membrane antigens and, as a result, death of cancer cells, has created various clinical benefits for the treatment of several human malignancies. In particular, CAR-T-cell-based immunotherapy is known as a critical approach for the treatment of patients with hematological malignancies such as acute lymphoblastic leukemia (ALL), multiple myeloma (MM), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), Hodgkin lymphoma (HL), and non-Hodgkin's lymphoma (NHL). However, CAR-T-cell therapy of hematological malignancies is associated with various side effects. There are still extensive challenges in association with further progress of this therapeutic approach, from manufacturing and engineering issues to limitations of applications and serious toxicities. Therefore, further studies are required to enhance efficacy and minimize adverse events. In the current review, we summarize the development of CAR-T-cell-based immunotherapy and current clinical antitumor applications to treat hematological malignancies. Furthermore, we will mention the current advantages, disadvantages, challenges, and therapeutic limitations of CAR-T-cell therapy.

Non-coding RNAs and glioblastoma: Insight into their roles in metastasis.

Glioma, also known as glioblastoma multiforme (GBM), is the most prevalent and most lethal primary brain tumor in adults. Gliomas are highly invasive tumors with the highest death rate among all primary brain malignancies. Metastasis occurs as the tumor cells spread from the site of origin to another site in the brain. Metastasis is a multifactorial process, which depends on alterations in metabolism, genetic mutations, and the cancer microenvironment. During recent years, the scientific study of non-coding RNAs (ncRNAs) has led to new insight into the molecular mechanisms involved in glioma. Many studies have reported that ncRNAs play major roles in many biological procedures connected with the development and progression of glioma. Long ncRNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) are all types of ncRNAs, which are commonly dysregulated in GBM. Dysregulation of ncRNAs can facilitate the invasion and metastasis of glioma. The present review highlights some ncRNAs that have been associated with metastasis in GBM. miRNAs, circRNAs, and lncRNAs are discussed in detail with respect to their relevant signaling pathways involved in metastasis.

Identification of a compound heterozygous missense mutation in LAMA2 gene from a patient with merosin-deficient congenital muscular dystrophy type 1A.

BACKGROUND: Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is occurred by mutations in LAMA2 gene that encodes the laminin α2 chain (merosin). MDC1A is a predominant subtype of congenital muscular dystrophy. Herein, we identified two missense mutations in LAMA2 gene in compound heterozygous status in an Iranian patient with MDC1A using whole-exome sequencing (WES). METHODS: In the present study, we evaluated genetic alterations in an Iranian 35-month-old boy with MDC1A and his healthy family using WES method. The identified mutations further confirmed by Sanger sequencing method. Finally, in silico analysis was conducted to further evaluation of molecular function of the identified genetic variants. RESULTS: We identified two potentially pathogenic missense mutations in compound heterozygous state (c.7681G>A p.Gly2561Ser and c.4840A>G p.Asn1614Asp) in LAMA2 gene as contributing to the MDC1A phenotype. The healthy parents of our proband are single heterozygous for identified mutations. These variants were found to be pathogenic by in silico analysis. CONCLUSIONS: In general, we successfully identified LAMA2 gene mutations in an Iranian patient with MDC1A using WES. The identified mutations in LAMA2 gene can be useful in genetic counseling, prenatal diagnosis, and predicting prognosis of MDC1A.

Electrospun gold nanorods/graphene oxide loaded-core-shell nanofibers for local delivery of paclitaxel against lung cancer during photo-chemotherapy method.

The combinations of photothermal therapy (PTT) and chemotherapy (CHT) have attracted increasing attention for cancer therapy. In the present study, paclitaxel as an anticancer drug and graphene oxide/gold nanorods (GO/Au NRs) were simultaneously loaded into the poly (tetramethylene ether) glycol based-polyurethane (PTMG-PU) (core)/chitosan (shell) nanofibers prepared by the coaxial electrospinning method. The potential of the synthesized nanofiber as a pH/temperature dual responsive carrier was investigated for the controlled release of paclitaxel against A549 lung cancer during PTT/CHT combined method. The synthesized core-shell nanofibers were characterized using SEM, TEM and XRD analysis. The drug encapsulation efficiency, drug release and kinetic studies were carried out. The compatibility of the synthesized core-shell nanofibers was also investigated. The cell viability of the synthesized nanofibers treated with A549 lung cancer cells was investigated under alone CHT, alone PTT and PTT/CHT method. The in vivo studies indicated that the PTT/CHT method demonstrated an optimal therapeutic effect on tumor inhibition without change in body weight. The obtained results demonstrated that the synthesized core-shell nanofibers would be used for lung cancer treatment under NIR irradiation in the future.

The Role of Non-coding Genome in Cancer-associated Fibroblasts; Stateof- the-Art and Perspectives in Cancer Targeted Therapy.

Cancer-associated fibroblasts (CAFs) are senescent fibroblasts in tumor nest, which trigger a signaling center to remodel a desmoplastic tumor niche. CAF's functions in cancer are closely similar to myofibroblasts during the wound healing process. They can produce cytokines, enzymes, and protein- or RNA-containing exosomes to alter the function of surrounding cells. Non-- coding RNAs, including microRNAs and long non-coding RNAs, modulate pathologic mechanisms in cancer. Dysregulation of these RNAs influences the formation and function of CAFs. Furthermore, it has been demonstrated that CAFs, by releasing non-coding RNAs-containing exosomes, affect the tumor cells' behavior. CAFs also secrete mediators such as chemokines to alter the expression of non-coding RNAs in the tumor microenvironment. This study aimed to discuss the role of non-coding RNAs in CAF development in cancer. Additionally, we have shed light on the therapeutic approaches to develop the strategies based on the alteration of non-coding RNAs in cancer.

Magnetic bioactive glasses/Cisplatin loaded-chitosan (CS)-grafted- poly (ε-caprolactone) nanofibers against bone cancer treatment.

The bioactive glasses (BGs)/Cisplatin and magnetic bioactive glasses (MBGs)/Cisplatin were doped into the chitosan (CS)-grafted- poly (ε-caprolactone) (PCL) nanofibers for controlled release of Cisplatin under various pH values and temperatures. The simultaneous effect of chemotherapy and hyperthermia was investigated against MG-63 osteosarcoma cells by treating of cells with Cs-g-PCL/MBGs/Cisplatin under an alternating magnetic field. The synthesized nanofibers were characterized using XRD, FTIR, 1H NMR, SEM, and EDX analysis. The bioactivity, and drug loading efficiency of fibers were investigated. There was no initial burst release of Cisplatin from BGs/Cisplatin and MBGs/Cisplatin loaded Cs-g-PCL/MBGs nanofibers and the Cisplatin release rate was accelerated under pH of 5.5 and temperature of 43 °C compared with physiological condition. The apoptotic/necrotic effect indicated that 100 µg mL-1 nanofibers was optimum for killing of MG-63 cells. The future researches could be focused on the application of nanofibers as an implantable device next to a bone tumor for bone cancer therapy in vivo.