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Humans have more than 270,000 lncRNAs. Among these, lncRNA HOXA-AS2 is considered a transformative gene involved in various cellular processes, including cell proliferation, apoptosis, migration, and invasion. Thus, it can be regarded as a potential tumor marker for both diagnosis and prognosis. Aberrant expression of lncRNAs is associated with many cancers, including hepatocellular carcinoma (HCC), gallbladder carcinoma (GBC), acute promyelocytic leukemia (APL), lung cancer (LC), prostate cancer (PC), osteosarcoma (OS), colorectal cancer (CRC), cervical cancer (CC), and acute myeloid leukemia (AML). Targeting lncRNAs could be a promising strategy to complement or replace current cancer treatments. As a non-coding oncogene, lncRNA HOXA-AS2 is implicated in multiple cancers and could serve as a potential biomarker for various malignancies. The tumor size and disease stage of several cancers are correlated with HOXA-AS2 expression. Silencing HOXA-AS2 effectively suppresses tumor cell proliferation and promotes apoptosis, thereby inhibiting the progression of multiple cancer types. The regulatory mechanisms of HOXA-AS2 include inducing epithelial-mesenchymal transition (EMT), overexpressing B-cell lymphoma-2 (Bcl-2) and MYC proto-oncogene (c-Myc), gene silencing, activating AKT-MMP signaling pathways, EZH2 and LSD1, and functioning within a competing endogenous RNA (ceRNA) regulatory network by competitively binding miRNAs. This review surveys recent research on the structure, biological functions, abnormal expression, regulatory mechanisms, and diagnostic and therapeutic potential of HOXA-AS2 in various cancers., Competing Interests: Declaration of Competing Interest The authors of this manuscript declare that there are no conflicts of interest, financial or otherwise, that could potentially influence or bias the work presented in this study. No funding sources or external support have been received for this research, and all authors have fully disclosed any relevant personal, professional, or financial relationships or interests that may potentially impact the integrity of the research. The authors affirm that the work was conducted in accordance with ethical and research standards, adhering to the highest level of scientific integrity and objectivity., (Copyright © 2025 Elsevier GmbH. All rights reserved.)

Background: Existing studies have suggested a link between oxidative stress levels and depression. Additionally, factors such as gender and conditions like hypertension have been shown to influence oxidative stress. This ten-year follow-up cohort study aims to examine the association between prooxidant-antioxidant balance (PAB) and the onset of depression and its symptoms in both hypertensive and normotensive individuals, while considering gender differences., Methods: The data for this study was obtained from the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study, a cohort study conducted in eastern Iran. Serum PAB levels were measured in 1702 hypertensive and 4096 normotensive individuals aged 35 to 65 years. After ten years, the participants' depression status was evaluated using the Beck questionnaire, and depression symptoms were investigated using the BDI-II structural model, which includes somatic, affective, and cognitive symptoms., Result: The analysis indicates that in hypertensive male participants, the highest tertile of PAB is associated with an increased risk of depression (β: 1.22, 95 % CI: -0.046, 2.485; P = 0.059) and symptoms of depression, including cognitive (β: 2.937, 95 % CI: 0.511, 5.362; P = 0.018) and somatic (β: 2.654, 95 % CI: 0.37, 4.939; P = 0.023) symptoms. However, there was no significant association between affective symptoms and PAB tertiles. Additionally, there was no significant link between depression and depressive symptoms in female hypertensive and normotensive individuals., Conclusion: In male hypertensive patients, but not in normotensive individuals of both genders and hypertensive women, depression and its associated symptoms, including somatic and cognitive symptoms, are associated with elevated levels of oxidative stress, as evidenced by higher serum PAB values. PAB is not associated with affective symptoms. Future studies should focus on the gender-specific nature of this relationship and work to clarify its underlying mechanisms., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Current treatments for rheumatoid arthritis produce untoward effects; thus, considerable effort has been made to recognize effective herbal medicines against the condition. In the present study, the therapeutic effect of Diospyros kaki fruit hydroalcoholic extract (DFHE) on complete Freund's adjuvant (CFA)-induced arthritis in rats was investigated. The extract was characterized using liquid chromatography-electrospray mass spectrometry (LC-ESIMS). Male Wistar rats were grouped as follows (eight rats in each): control, CFA, CFA + indomethacin (5 mg/kg), CFA + DFHE (50 mg/kg), and CFA + DFHE (100 mg/kg). Paw volume, mechanical allodynia, thermal hyperalgesia, and arthritis score were evaluated. Serum levels of malondialdehyde (MDA), thiol groups, tumor necrosis factor-alpha (TNF-α), as well as glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were evaluated. Carotenoids were found to be the major components of DFHE. Administration of DFHE (100 mg/kg) significantly decreased arthritis score, paw volume, and thermal hyperalgesia, and improved mechanical allodynia. MDA and TNF-α levels were decreased while thiol levels and SOD and GPx activities were increased in DFHE-treated groups compared to the CFA group. These results suggest that D. kaki extract caused an improvement in clinical signs of rheumatoid arthritis symptoms possibly through suppression of oxidative stress and inflammation., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Food Science & Nutrition published by Wiley Periodicals LLC.)

All-trans retinoic acid (ATRA) has promising activity against breast cancer. However, the exact mechanisms of ATRA's anticancer effects remain complex and not fully understood. In this study, a network pharmacology and molecular docking approach was applied to identify key target genes related to ATRA's anti-breast cancer activity. Gene/disease enrichment analysis for predicted ATRA targets was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID), the Comparative Toxicogenomics Database (CTD), and the Gene Set Cancer Analysis (GSCA) database. Protein-Protein Interaction Network (PPIN) generation and analysis was conducted via Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and cytoscape, respectively. Cancer-associated genes were evaluated using MyGeneVenn from the CTD. Differential expression analysis was conducted using the Tumor, Normal, and Metastatic (TNM) Plot tool and the Human Protein Atlas (HPA). The Glide docking program was used to predict ligand-protein binding. Treatment response predication and clinical profile assessment were performed using Receiver Operating Characteristic (ROC) Plotter and OncoDB databases, respectively. Cytotoxicity and gene expression were measured using MTT/fluorescent assays and Real-Time PCR, respectively. Molecular functions of ATRA targets (n = 209) included eicosanoid receptor activity and transcription factor activity. Some enriched pathways included inclusion body myositis and nuclear receptors pathways. Network analysis revealed 35 hub genes contributing to 3 modules, with 16 of them were associated with breast cancer. These genes were involved in apoptosis, cell cycle, androgen receptor pathway, and ESR-mediated signaling, among others. CCND1, ESR1, MMP9, MDM2, NCOA3, and RARA were significantly overexpressed in tumor samples. ATRA showed a high affinity towards CCND1/CDK4 and MMP9. CCND1, ESR1, and MDM2 were associated with poor treatment response and were downregulated after treatment of the breast cancer cell line with ATRA. CCND1 and ESR1 exhibited differential expression across breast cancer stages. Therefore, some part of ATRA's anti-breast cancer activity may be exerted through the CCND1/CDK4 complex., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Hepatitis B is still one of the most important infectious diseases among humans, which is considered a serious threat to their lives. Early diagnosis of this disease can be an effective measure in stopping the chain of transmission and treatment of the disease. In this review study, an attempt has been made to explain the use of biosensors as a fast, high-efficiency, and low-cost method in diagnosis. The biosensors prepared for hepatitis detection included DNA-based, aptamers-based, protein-based, enzyme-based, antibody-based, and polymers-based biosensors, each of which had different advantages. The results of this review showed that almost all introduced biosensors had an acceptable performance. However, we suggest that aptamers are desirable for biosensing applications because they can change their structure to properly bind to their target, are cost-effective to prepare, and are highly sensitive., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Therapeutic vaccinations are designed to prevent cancer by inducing immune responses against tumor antigens. in cancer cells, tumor-associated antigens (TAA) or tumor-specific (mutated) derived peptides are presented within the clefts of main histocompatibility complex (MHC) class I or class II molecules, they either activate cytotoxic T-lymphocytes (CTLs), CD4 + T or CD8 + T lymphocytes, which release cytokines that can suppress tumor cells growth. In cancer immunotherapies, CD8 + T lymphocytes are a major mediator of tumor repression. The effect of peptide-based vaccinations on cytokines in the activating CD8 + T cell against targeted tumor antigens is the subject of this review. It is believed that peptide-based vaccines increased IFN-γ, TNF-α, IL-2, and IL-12, secreting CTL line by interacting with dendritic cell (DC), supposed to stimulate immune system. Additionally, mechanisms of CTL activation and dysfunction were also studied. According to most of the data resulted from in vivo and in vitro research works, it is assumed that peptide-based vaccines increased IFN-γ, TNF-α, IL-2, and IL-12., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

In recent years, the field of cancer treatment has witnessed remarkable breakthroughs that have revolutionized the landscape of care for cancer patients. While traditional pillars such as surgery, chemotherapy, and radiation therapy have long been available, a cutting-edge therapeutic approach called CAR T-cell therapy has emerged as a game-changer in treating multiple myeloma (MM). This novel treatment method complements options like autologous stem cell transplants and immunomodulatory medications, such as proteasome inhibitors, by utilizing protein complexes or anti-CD38 antibodies with potent complement-dependent cytotoxic effects. Despite the challenges and obstacles associated with these treatments, the recent approval of the second FDA multiple myeloma CAR T-cell therapy has sparked immense promise in the field. Thus far, the results indicate its potential as a highly effective therapeutic solution. Moreover, ongoing preclinical and clinical trials are exploring the capabilities of CAR T-cells in targeting specific antigens on myeloma cells, offering hope for patients with relapsed/refractory MM (RRMM). These advancements have shown the potential for CAR T cell-based medicines or combination therapies to elicit greater treatment responses and minimize side effects. In this context, it is crucial to delve into the history and functions of CAR T-cells while acknowledging their limitations. We can strategize and develop innovative approaches to overcome these barriers by understanding their challenges. This article aims to provide insights into the application of CAR T-cells in treating MM, shedding light on their potential, limitations, and strategies employed to enhance their efficacy., (© 2024. The Author(s).)

Background: The progression of acute limb ischemia (ALI) is being significantly influenced by changes in immune system function. The study aimed to determine the dominant immune cell responses (Th1 or Th2) in ALI patients by measuring serum levels of IL-4, IL-12, and IFN-γ. Previous studies indicate altered cytokine levels in cerebral ischemia, but there is no prior research on these cytokines in ALI patients., Methods: This study involved 34 patients with ALI and 34 healthy controls. Blood samples were analyzed for hematological factors such as erythrocyte sedimentation rate (ESR), white blood cell (WBC) count, red blood cell (RBC) count, platelet (Plt) count, hemoglobin (Hb), and hematocrit (HCT). The levels of serum cytokines IL-4, IL-12, and IFN-γ were measured in both patients and control subjects using enzyme-linked immunosorbent assay (ELISA). The statistical analyses were conducted using SPSS and GraphPad Prism., Results: The results showed that serum levels of IL-4 in ALI patients did not significantly differ from those in control groups. Acute limb ischemia exhibited significantly elevated levels of IL-12 and IFN-γ compared to healthy individuals. In addition, no correlation between the production of cytokines and the hematological parameters was found., Conclusions: Th1 responses are believed to play a role in the pathogenesis of ALI, but further research is needed to fully understand their exact role., Competing Interests: No potential conflict of interest was reported by the authors.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse effect of cisplatin. The current study aimed to determine whether PEGylated nanoliposomal cisplatin can limit CIPN in an animal model., Methods: Cisplatin-loaded PEGylated liposome nanoparticles (Cis-PL) were produced as a combination of lecithin, cholesterol, and DSPE-mPEG2000 in a molar ratio of 50:45:5 and were characterized by polydispersity index (PDI), zeta potential, Field emission scanning electron microscopy (FESEM) analysis, as well as encapsulation efficiency (EE). Fifteen male rats were provided and randomly divided into 3 groups including Cis-PL group, cisplatin group, and control group. Behavioural tests (hot-plate test and acetone drop test) were used for evaluating CIPN. Moreover, oxidative stress markers and histopathological analysis were applied. Treatment-related toxicity was assessed by haematological analysis as well as liver and renal function tests., Results: Cis-PL had an average particle size of 125.4, PDI of 0.127, and zeta potential of -40.9 mV. Moreover, the Cis-PL exhibited a high EE as well as low levels of leakage rate at 25 °C. In a hot-plate test, paw withdrawal latency was longer in Cis-PL group in comparison to rats treated with cisplatin. A lower number of withdrawal responses was detected during acetone drop test in Cis-PL group than in cisplatin-treated rats. Assessment of oxidative stress markers showed that Cis-PL could improve oxidative stress. Additionally, histopathological assessment demonstrated that the number of satellite cells was significantly reduced in the dorsal root ganglion (DRG) of Cis-PL-treated rats compared with those treated with cisplatin. The cisplatin group had elevated white blood cells counts, reduced platelet counts, and higher levels of bilirubin, ALT (alanine aminotransferase, and AST (aspartate aminotransferase), and creatinine compared with the control group, which was ameliorated in Cis-PL group., Conclusions: Data from the current study support the previous hypothesis that Cisplatin-loaded PEGylated liposome could be a promising solution for CIPN in the future by modulating oxidative stress and preventing glial cell activation in DRG, suggesting further clinical studies to investigate the efficacy of this agent and its potential application in clinical practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The lymphatic system, crucial for tissue fluid balance and immune surveillance, can be severely impacted by disorders that hinder its activities. Lymphatic malformations (LMs) are caused by fluid accumulation in tissues owing to defects in lymphatic channel formation, the obstruction of lymphatic vessels or injury to lymphatic tissues. Somatic mutations, varying in symptoms based on lesions' location and size, provide insights into their molecular pathogenesis by identifying LMs' genetic causes. In this review, we collected the most recent findings about the role of genetic and inflammatory biomarkers in LMs that control the formation of these malformations. A thorough evaluation of the literature from 2000 to the present was conducted using the PubMed and Google Scholar databases. Although it is obvious that the vascular endothelial growth factor receptor 3 mutation accounts for a significant proportion of LM patients, several mutations in other genes thought to be linked to LM have also been discovered. Also, inflammatory mediators like interleukin-6, interleukin-8, tumor necrosis factor-alpha and mammalian target of rapamycin are the most commonly associated biomarkers with LM. Understanding the mutations and genes expression responsible for the abnormalities in lymphatic endothelial cells could lead to novel therapeutic strategies based on molecular pathways., (© 2024 John Wiley & Sons Ltd.)

The formation of vascular networks consisting of arteries, capillaries, and veins is vital in embryogenesis. It is also crucial in adulthood for the formation of a functional vasculature. Cerebral arteriovenous malformations (CAVMs) are linked with a remarkable risk of intracerebral hemorrhage because arterial blood is directly shunted into the veins before the arterial blood pressure is dissipated. The underlying mechanisms responsible for arteriovenous malformation (AVM) growth, progression, and rupture are not fully known, yet the critical role of inflammation in AVM pathogenesis has been noted. The proinflammatory cytokines are upregulated in CAVM, which stimulates overexpression of cell adhesion molecules in endothelial cells (ECs), leading to improved leukocyte recruitment. It is well-known that metalloproteinase-9 secretion by leukocytes disrupts CAVM walls resulting in rupture. Moreover, inflammation alters the angioarchitecture of CAVMs by upregulating angiogenic factors impacting the apoptosis, migration, and proliferation of ECs. A better understanding of the molecular signature of CAVM might allow us to identify biomarkers predicting this complication, acting as a goal for further investigations that may be potentially targeted in gene therapy. The present review is focused on the numerous studies conducted on the molecular signature of CAVM and the associated hemorrhage. The association of numerous molecular signatures with a higher risk of CAVM rupture is shown through inducing proinflammatory mediators, as well as growth factors signaling, Ras-mitogen-activated protein kinase-extracellular signal-regulated kinase, and NOTCH pathways, which are accompanied by cellular level inflammation and endothelial alterations resulting in vascular wall instability. According to the studies, it is assumed that matrix metalloproteinase, interleukin-6, and vascular endothelial growth factor are the biomarkers most associated with CAVM and the rate of hemorrhage, as well as diagnostic methods, with respect to enhancing the patient-specific risk estimation and improving treatment choices., (© 2023 John Wiley & Sons Ltd.)

The occurrence of a novel coronavirus known as severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), created a serious challenge worldwide. SARS-CoV-2 has high infectivity, the ability to be transmitted even during the asymptomatic phase, and relatively low virulence, which has resulted in rapid transmission. SARS-CoV-2 can invade epithelial cells, hence, many patients infected with SARS-CoV-2 have suffered from vascular diseases (VDs) in addition to pulmonary manifestations. Accordingly, SARS-CoV-2 may can worsen the clinical condition of the patients with pre-existing VDs. Endothelial cells express angiotensin-converting enzyme 2 (ACE2). ACE2 is a biological enzyme that converts angiotensin (Ang)- 2 to Ang-(1-7). SARS-CoV-2 uses ACE2 as a cell receptor for viral entry. Thus, the SARS-CoV-2 virus promotes downregulation of ACE2, Ang-(1-7), and anti-inflammatory cytokines, as well as, an increase in Ang-2, resulting in pro-inflammatory cytokines. SARS-CoV-2 infection can cause hypertension, and endothelial damage, which can lead to intravascular thrombosis. In this review, we have concentrated on the effect of SARS-CoV-2 in peripheral vascular diseases (PVDs) and ACE2 as an enzyme in Renin-angiotensin aldosterone system (RAAS). A comprehensive search was performed on PubMed, Google Scholar, Scopus, using related keywords. Articles focusing on ("SARS-CoV-2", OR "COVID-19"), AND ("Vascular disease", OR "Peripheral vascular disease", OR interested disease name) with regard to MeSH terms, were selected. According to the studies, it is supposed that vascular diseases may increase susceptibility to severe SARS-CoV-2 infection due to increased thrombotic burden and endothelial dysfunction. Understanding SARS-CoV-2 infection mechanism and vascular system pathogenesis is crucial for effective management and treatment in pre-existing vascular diseases., Competing Interests: Declaration of Competing Interest No potential conflict of interest was reported by the authors., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Preclinical models are extensively employed in cancer research because they can be manipulated in terms of their environment, genome, molecular biology, organ systems, and physical activity to mimic human behavior and conditions. The progress made in in vivo cancer research has resulted in significant advancements, enabling the creation of spontaneous, metastatic, and humanized mouse models. Most recently, the remarkable and extensive developments in genetic engineering, particularly the utilization of CRISPR/Cas9, transposable elements, epigenome modifications, and liquid biopsies, have further facilitated the design and development of numerous mouse models for studying cancer. In this review, we have elucidated the production and usage of current mouse models, such as xenografts, chemical-induced models, and genetically engineered mouse models (GEMMs), for studying esophageal cancer. Additionally, we have briefly discussed various gene-editing tools that could potentially be employed in the future to create mouse models specifically for esophageal cancer research., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Chemotherapy-induced peripheral neuropathy (CIPN) is an important adverse effect of treatment with oxaliplatin (OXA). We have developed PEGylated nanoliposomal oxaliplatin (OXA-LIP) and tested its activity in an animal model of CIPN. OXA-LIPs were prepared using a combination of egg yolk lecithin, cholesterol, and DSPE-mPEG2000 (at ratios 400, 80, and 27 mg). These liposomes were characterized using several different methods (e.g., polydispersity index (PDI), and zeta potential, FESEM). The in vivo study was performed in 15 male rats comprising three groups: a negative control (normal saline) OXA, and OXA-LIP. These were injected intraperitoneally at a concentration of 4 mg/kg on two consecutive days every week, for 4 weeks. After that, CIPN was assessed using the hotplate and acetonedropmethods. Oxidative stress biomarkers such as SOD, catalase, MDA, and TTG were measured in the serum samples. The functional disturbances of the liver and kidney were assessed by measuring the serum levels of ALT, AST, creatinine, urea, and bilirubin. Furthermore, hematological parameters were determined in the three groups. The OXA-LIP had an average particle size, PDI, and zeta potential of 111.2 ± 1.35 nm, 0.15 ± 0.045, and -52.4 ± 17 mV, respectively. The encapsulation efficiency of OXA-LIP was 52% with low leakage rates at 25 °C.Thermal hyperalgesia changes showed OXA has significant effects in the induction of neuropathy on days 7, 14, and 21 compared to the control group. OXA had a significantly greater sensitivity than the OXA-LIP and control groups in the thermal allodynia test (P < 0.001). OXA-LIP administration did not show significant effects on the changes of oxidative stress, biochemical factors, and cell count. Our findings provide a proof of concept on the potential application of oxaliplatin encapsulated with PEGylated nanoliposome to ameliorate the severity of neuropathy, supporting further studies in clinical phases to explore the value of this agent for Chemotherapy-induced peripheral neuropathy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Colorectal cancer (CRC) is a highly widespread malignancy and ranks as the second most common cause of cancer-related mortality., Objective: Cancer patients, including those with CRC, who undergo chemotherapy, are often treated with platinum- based anticancer drugs such as oxaliplatin (OXA). Nevertheless, the administration of OXA is associated with a range of gastrointestinal problems, neuropathy, and respiratory tract infections. Hence, it is necessary to devise a potential strategy that can effectively tackle these aforementioned challenges. The use of nanocarriers has shown great potential in cancer treatment due to their ability to minimize side effects, target drugs directly to cancer cells, and improve drug efficacy. Furthermore, numerous studies have been published regarding the therapeutic efficacy of nanoparticles in the management of colorectal cancer., Methods: In this review, we present the most relevant nanostructures used for OXA encapsulation in recent years, such as solid lipid nanoparticles, liposomes, polysaccharides, proteins, silica nanoparticles, metal nanoparticles, and synthetic polymer-carriers. Additionally, the paper provides a summary of the disadvantages and limits associated with nanoparticles., Results: The use of different carriers for the delivery of oxaliplatin increased the efficiency and reduced the side effects of the drug. It has been observed that the majority of research investigations have focused on liposomes and polysaccharides., Conclusion: This potentially auspicious method has the potential to enhance results and enhance the quality of life for cancer patients undergoing chemotherapy. However, additional investigation is required to ascertain the most suitable medium for the transportation of oxaliplatin and to assess its efficacy through clinical trials., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Colorectal cancer (CRC) is the second most common cause of cancer mortality, with approximately 1.9 million new cases and 0.9 million deaths globally in 2020. One of the potential ways to treat colorectal cancer may be through the use of molecular methods to induce cell apoptosis. Apoptosis is a natural cellular event that regulates the growth and proliferation of body cells and prevents cancer. In this pathway, several molecules are involved; one group promotes this process, and some molecules that are representative of inhibitors of apoptosis proteins (IAPs) inhibit apoptosis. The most important human IAPs include c-IAP1, c-IAP2, NAIP, Survivin, XIAP, Bruce, ILP-2, and Livin. Several studies have shown that the inhibition of IAPs may be useful in cancer treatment. MicroRNAs (miRNAs) may be effective in regulating the expression of various proteins, including those of the IAPs family; they are a large subgroup of non-coding RNAs that are evolutionarily conserved. Therefore, in this review, the miRNAs that may be used to target IAPs in colorectal cancer were discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

(1) Background: Mounting evidence supports the idea that one of the most critical agents in controlling gene expression could be long non-coding RNAs (lncRNAs). Upregulation of lncRNA is observed in the different processes related to pathologies, such as tumor occurrence and development. Among the crescent number of lncRNAs discovered, FLVCR1-AS1 and FBXL19-AS1 have been identified as oncogenes in many cancer progression and prognosis types, including cholangiocarcinoma, gastric cancer, glioma and glioblastoma, hepatocellular carcinoma, lung cancer, ovarian cancer, breast cancer, colorectal cancer, and osteosarcoma. Therefore, abnormal FBXL19-AS1 and FLVCR1-AS1 expression affect a variety of cellular activities, including metastasis, aggressiveness, and proliferation; (2) Methods: This study was searched via PubMed and Google Scholar databases until May 2022; (3) Results: FLVCR1-AS1 and FBXL19-AS1 participate in tumorigenesis and have an active role in impacting several signaling pathways that regulate cell proliferation, migration, invasion, metastasis, and EMT; (4) Conclusions: Our review focuses on the possible molecular mechanisms in a variety of cancers regulated by FLVCR1-AS1 and FBXL19-AS1. It is not surprising that there has been significant interest in the possibility that these lncRNAs might be used as biomarkers for diagnosis or as a target to improve a broader range of cancers in the future.

Background: To recognize the action of pharmacologically approved anticancer drugs in biological systems, information regarding its pharmacokinetics, such as its transport within the plasma and delivery to its target site, is essential. In this study, we have tried to collect and present complete information about how these drugs bind to human serum albumin (HSA) protein. HSA functions as the main transport protein for an enormous variety of ligands in circulation and plays a vital role in the efficacy, metabolism, distribution, and elimination of these agents., Methods: Therefore, this study includes information about the quenching constant, the binding constant obtained from Stern-Volmer and Hill equations, and molecular docking., Results: Molecular docking was carried out to detect the binding models of HSA-anticancer drugs and the binding site of the drugs in HSA, which further revealed the contribution of amino acid residues of HSA in the drug complex binding., Conclusion: This review study showed that site I of the protein located in domain II can be considered the most critical binding site for anticancer drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This article provides a brief overview of DNA vaccines. First, the basic DNA vaccine design strategies are described, then specific issues related to the industrial production of DNA vaccines are discussed, including the production and purification of DNA products such as plasmid DNA, minicircle DNA, minimalistic, immunologically defined gene expression (MIDGE) and Doggybone™. The use of adjuvants to enhance the immunogenicity of DNA vaccines is then discussed. In addition, different delivery routes and several physical and chemical methods to increase the efficacy of DNA delivery into cells are explained. Recent preclinical and clinical trials of DNA vaccines for COVID-19 are then summarized. Lastly, the advantages and obstacles of DNA vaccines are discussed., (© 2021 Future Medicine Ltd.)

Sorafenib tosylate (SORt) is an oral multikinase inhibitor used for treatment of advanced renal cell, liver, and thyroid cancers. In this study, this drug was synthesized and its antiproliferative activities against HCT116 and CT26 cells were assessed. The interaction of SORt with β-lactoglobulin (BLG) was studied using different fluorescence techniques, circular dichroism (CD), zeta potential measurements, and docking simulation. The results of infrared (IR), mass, H NMR, and C NMR spectra demonstrated that the drug was produced with high quality, purity, and efficiency. SORt showed potent cytotoxicity against HCT116 and CT26 cells with IC 50 of 8.12 and 5.42 μM, respectively. For BLG binding of SORt, the results showed that static quenching was the cause of the high affinity drug-protein interaction. Three-dimensional fluorescence and synchronous spectra indicated that SORt conformation was changed at different levels. CD suggested that the α-helix content remained almost constant in the BLG-SORt complex, whereas random coil content decreased. Zeta potential values of BLG were more positive after binding with SORt, due to electrostatic interactions between BLG and SORt. Thermodynamic parameters confirmed van der Waals and hydrogen bond interactions in the complex formation. Molecular modelling predicted the presence of hydrogen bonds and electrostatic forces in the BLG-SORt system, which was consistent with the experimental results., (© 2020 John Wiley & Sons, Ltd.)

Background: Interactions of drugs with DNA and proteins may modify their biological activities and conformations, which effect transport and biological metabolism of drugs., Objective: In this study the interaction of anticancer drug regorafenib (REG) with calf thymus-DNA (ct-DNA) and human serum albumin (HSA) has been investigated Methods: Hence, for the first time, it was discovered interaction between REG with DNA and HSA using multi-spectroscopic, zeta potential measurements and molecular docking method., Results and Discussion: DNA displacement studies showed that REG does not have any effect on acridine orange and methylene blue bound DNA, though it was substantiated by displacement studies with Hoechst (as groove binder). Furthermore, the different concentrations of REG induce slight changes in the viscosity of ct-DNA. Zeta potential parameters indicated that hydrophobic interaction plays a major role in the DNA-REG complex. Results obtained from molecular docking demonstrate that the REG prefers to bind on the minor groove of DNAs than that of the major groove. Binding properties of HSA reveal that intrinsic fluorescence of HSA could be quenched by REG in a static mode. The competitive experiments in the presence of warfarin and ibuprofen (as site markers) suggested that the binding site of REG to HSA was most probably located in the subdomain IIA. Measurements of the zeta potential indicated that REG bound to HSA mainly by both electrostatic and hydrophobic interactions. It was found on docking procedures that REG could fit well into HSA subdomain IIA, which confirmed the experimental results., Conclusion: In conclusion, REG can be delivered by HSA in a circulatory system and affect DNA as potential target., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Extremely low-frequency electromagnetic fields (ELF-EMFs) are abundantly produced in modern societies. In recent years, interest in the possible effects of ELF-EMFs on the immune system has progressively increased., Objective: To examine the effects of ELF-EMFs with magnetic flux densities of 1, 100, 500, and 2000 μT on the serum levels of interleukin (IL)-9, IL-10, and tumor necrosis factor-alpha (TNF-α)., Methods: 80 adult male rats were exposed to ELF-EMFs at a frequency of 50 Hz for 2 h/day for 60 days. The serum cytokines were measured at two phases of pre- and post-stimulation of the immune system by human serum albumin (HSA)., Results: Serum levels of IL-9 and TNF-α, as pro-inflammatory cytokines, were decreased due to 50 Hz EMFs exposure compared with the controls in the pre- and post-stimulation phases. On the contrary, exposures to 1 and 100 μT 50 Hz EMFs increased the levels of antiinflammatory cytokine, and IL-10 only in the pre-stimulation phase. In the post-stimulation phase, the mean level of serum IL-10 was not changed in the experimental groups., Conclusion: The magnetic flux densities of 1 and 100 μT 50 Hz EMFs had more immunological effects than EMFs with higher densities. Exposure to 50 Hz EMFs may activate anti-inflammatory effects in rats, by down-modulation of pro-inflammatory cytokines (IL-9 and TNF-α) and induction of the anti-inflammatory cytokine (IL-10).

In this study, Farnesiferol C was introduced as an anti-colon cancer agent. Its cytotoxicity was investigated on two cancer cell lines, HCT116 and CT26, and mesenchymal stem cells (MSCs) as normal cells employing MTT assay. Moreover, Farnesiferol C interactions with ct-DNA and HSA were investigated by various techniques. The IC 50 values of Farnesiferol C on HCT116 and CT26 cells were 42 and 46 μM, respectively, while its IC 50 value on MSCs cells was 92 μM, indicating that Farnesiferol C was more efficacious against cancer cell lines than normal cells. DNA competitive binding studies, viscosity and zeta potential measurements confirmed that Farnesiferol C bound to DNA through intercalation binding. HSA binding investigations revealed that there were two different binding sites for Far C on HSA with higher binding affinity in site 2 compared to site 1. Furthermore, Farnesiferol C could bind to HSA and quench its intrinsic fluorescence in a static quenching mechanism, with a distance of 2.54 nm. Competitive binding in the presence of warfarin and ibuprofen was carried out and the resulting quenching constant was strongly changed in the presence of warfarin. Consequently, Farnesiferol C most probably will be located within sub-domain IIA. In this study, molecular modeling buttressed and confirmed our laboratory results. Conclusively, we proposed that DNA is an appropriate target for Farnesiferol C. Therefore, Farnesiferol C and its semisynthetic analogues can be one of the priority innovations in research on anticancer drugs.

This study was carried out to evaluate the binding interaction of gefitinib (GEF) with human serum albumin (HSA) and calf thymus DNA (ct-DNA) using fluorescence, UV-Visible, zeta potential measurements and molecular docking methods in order to understand its pharmacokinetic mechanism. By increasing the temperature, a steady decrease in Stern-Volmer quenching constants was observed for HSA binding properties; this indicates a static type of fluorescence quenching. Negative values were calculated for Gibbs free energy (ΔG), enthalpy (ΔH), and entropy (ΔS) changes, indicating that the reaction is spontaneous and enthalpy-driven. Probe competitive experimental results showed that GEF contains the same binding site as warfarin and are consistent with modeling results. The zeta potential of the HSA increased with increasing GEF, which represents the presence of electrostatic interactions in the system. DNA binding properties were investigated in the presence of three probes. The experimental results showed that by increasing GEF to DNA-AO (acridine-orange) and DNA-MB (methylene-blue) system, the fluorescence intensity and absorbance spectra had no considerable change. Furthermore, with the addition of GEF to DNA, the zeta potential decreased gradually, indicating that the hydrophobic interaction between the GEF and the bases of DNA is the major factor. Thus, GEF can bind to DNA via a groove binding mode. It was also found that GEF entered into the minor groove in the A-T rich region of DNA fragment and bind via van der-Waals forces and three H-bond with double strands of DNA. This is in good agreement with experimental results.

Background: The onset of acute toxoplasmosis in pregnant women may pose a risk to their growing fetuses. The timely diagnosis of infection in managing the disease and preventing its harmful consequences on the fetus is very important. Therefore, the study was conducted to identify acute toxoplasmosis in the pregnant women by detecting the specific IgM antibody and Toxoplasma gondii B1 gene., Methods: A total of 653 serum samples of women who attended to Fatemieh Hospital of Hamadan University of Medical Sciences were tested for IgG antibodies against Toxoplasma gondii by enzyme-linked immunosorbent as-say (ELISA). The IgG positive specimens were further examined for IgM by ELISA and polymerase chain reaction (PCR) for B1 gene. In the second phase, change in IgG titers was evaluated on 47 IgG positive samples after two weeks., Results: ELISA data showed that 167 out of 653 and 2 out of 167 samples were positive for IgG (25.6%) and IgM (1.2%), respectively. However, PCR detection showed that 36 cases (21.6%) were positive for the B1 gene. Seven out of 47 IgG positive samples showed an increase in the antibody titer and positive for the B1 gene. The most cases of IgG positives and the B1 gene samples were associated with the third trimester of pregnancy with 49.7% and 14%, respectively, and the most common abundance of the B1 gene was 14.4% in the age group of 26 - 35. The most commonly reported clinical symptoms in the B1 gene-positive women were nausea 15 (41.7%), cough 13 (36.1%), headache 12 (33.3%), and vomiting 11 (30.5%)., Conclusions: Using PCR and the B1 gene in serum samples of pregnant women to detect acute toxoplasmosis is a more appropriate and accurate method than IgM antibody.

Background: Congenital toxoplasmosis is an important disease that occurs when pregnant women become infected with Toxoplasma gondii during pregnancy. The aim of this study was to investigate the presence of T. gondii B1 gene in placental tissues of IgM seronegative women., Materials and Methods: In this research, chronic toxoplasmosis was identified through examination of blood samples in a group of pregnant women by anti-Toxoplasma IgG and IgM ELISA and nested-PCR techniques. IgG avidity test was used to estimate the onset of infection in some pregnant women with chronic infection. After delivery, some umbilical cord and neonatal blood were tested by anti-Toxoplasma IgM ELISA, and also the B1 gene of T. gondii was investigated in their placental tissue by nested-PCR. Some factors such as blood sampling time and some clinical symptoms experienced during pregnancy were recorded., Results: One hundred and sixty seven out of 653 (25.6%) pregnant women were positive for anti-Toxoplasma IgG. Of them, 165 (98.8%) were negative for anti-T. gondii IgM. Six out of 10 (60%) placental tissues from IgG seropositive, IgM seronegative women were positive for T. gondii B1 gene, while anti-Toxoplasma IgM was negative in the umbilical cord and neonatal blood samples. The results of IgG avidity test showed low avidity in one and high avidity in two women's samples. The B1 gene was not found in the blood samples of any of the six mothers. The most symptoms experienced during pregnancy were headache and nausea., Conclusion: The detection of B1 gene in placental tissues of the healthy newborn infants reiterates that presence of T. gondii in the placenta does not always result in congenital toxoplasmosis.

Extremely low frequency electromagnetic field (ELF-EMF) is produced extensively in modern technologies. Numerous in vitro and in vivo studies have shown that ELF-EMF has both stimulatory and inhibitory effects on the immune system response. This review was conducted on effects of ELF-EMF on cytokines of innate and adaptive immunity. Mechanisms of ELF-EMF, which may modulate immune cell responses, were also studied. Physical and biological parameters of ELF-EMF can interact with each other to create beneficial or harmful effect on the immune cell responses by interfering with the inflammatory or anti-inflammatory cytokines. According to the studies, it is supposed that short-term (2-24 h/d up to a week) exposure of ELF-EMF with strong density may increase innate immune response due to an increase of innate immunity cytokines. Furthermore, long-term (2-24 h/d up to 8 years) exposure to low-density ELF-EMF may cause a decrease in adaptive immune response, especially in T h 1 subset.

The study investigated the effect of extremely low-frequency electromagnetic fields (ELF-EMFs) exposure at different magnetic flux densities on genes expression of transcription factor Maf (c-Maf), signal transducer and activator of transcription 6 (STAT6), and retinoid-related orphan receptor alpha (RORα) in the spleen and thymus of rats. Eighty adult male rats were separated into four ELF-EMFs exposed and were exposed to magnetic flux densities of 1, 100, 500, and 2000 µT at a frequency of 50 Hz for 2 h daily for up to 60 d. All rats were intraperitoneally immunized on d 31, 44, and 58 of exposure. The experimental results showed that the expression levels of c-Maf, STAT6, and RORα in the thymus were not significantly changed at different magnetic flux densities. The expression levels of RORα and c-Maf were significantly downregulated at the densities of 1 and 100 µT, while the expression of STAT6 was only significantly decreased at the density of 100 µT. In conclusion, low magnetic flux densities of ELF-EMFs may reduce the expression levels of c-Maf, STAT6, and RORα genes in the spleen.

Bioactive peptides have been defined as specific protein fragments that have numerous biological activities. The aim of this study was to introduce three multifunctional peptides. Hence, we used rabbit lung angiotensin converting enzyme (ACE) inhibitor peptide AFKDEDTEEVPFR to prepare two analogous peptides KDEDTEEVP and KDEDTEEVH. ACE inhibitory, antioxidant, and antimicrobial activities of three synthetic peptides were investigated. Among the three peptides, KDEDTEEVP exhibited the highest ACE inhibitory activity with IC 50 value of 69.63 ± 2.51 μM. Furthermore, the results of fluorescence spectroscopy and molecular modeling showed that KDEDTEEVP had more affinity to ACE than other peptides. The peptide of KDEDTEEVH showed the strongest antioxidant scavenging capacity on DPPH radicals (EC 50  = 135 ± 9.62 μM), hydroxyl radicals (EC 50  = 144 ± 8.73 μM), and ABTS radicals (EC 50  = 62 ± 4.52%). Moreover, it showed the highest activity in iron-chelating test (EC 50  = 226 ± 14.13 μM) and could also effectively inhibit the peroxidation of linoleic acid. The antimicrobial activity results showed that KDEDTEEVH had higher efficiency against Gram-positive than Gram-negative bacteria with MIC values of higher than 205 ± 10.75 μM. Although there was not a direct correlation between ACE inhibitor and antioxidant activity for analogous peptides, both analogous peptides exhibited more efficiency than the mother peptide. Thus, they can be considered as multifunctional peptides and would be beneficial ingredient to be used in food and drug industry.

The study aimed to determine effect of extremely low frequency (50 Hz) electromagnetic fields (ELF-EMFs) exposure on serum levels of interleukin-17 (IL-17) and transforming growth factor-β (TGF-β) as signature cytokines of Th17 and regulatory T (Treg) cells, respectively. Retinoid-related orphan receptor γT and transcription factor forkhead box P3 (Foxp3) expression levels as lineage defining of Th17 and Treg cells were also assessed in the spleen and thymus. Eighty male rats were separated into 4 exposed groups (1, 100, 500, and 2,000 μT magnetic flux intensities) and a control. All rats were immunized by human serum albumin after 1 month of the exposure and the experiment was continued in the same manner for 1 month more. The results demonstrated that the weight of thymuses was significantly declined at intensity of 2,000 μT. At the preimmunization phase, the serum levels of IL-17 and TGF-β were significantly decreased at intensities of 1 and 100 μT. The expression of Foxp3 was also downregulated at intensities of 1 and 100 μT. In conclusion, low intensities of ELF-EMF may reduce the serum levels of IL-17 and TGF-β and downregulate the expression of Foxp3 in spleen.

Background: One of the consequences of toxoplasmosis is the risk of passing it from mother to fetus and the onset of congenital toxoplasmosis during pregnancy. The purpose of this study was to evaluate the B1 gene of Toxoplasma gondii in the placental tissues of pregnant women with acute toxoplasmosis., Materials and Methods: The study was a cross-sectional study. Serum samples of pregnant women who attended to Fatemieh Hospital of Hamadan University of Medical Sciences were tested for immunoglobulin G (IgG) antibodies against T. gondii by enzyme-linked immunosorbent assay. Then, polymerase chain reaction was used to identify the specific B1 gene of T. gondii in IgG seropositive women. The placental tissues of the pregnant women with positive serum B1 gene examined for this gene. Anti- Toxoplasma immunoglobulin M (IgM) was performed on the umbilical cord and neonate blood., Results: Anti- Toxoplasma IgG was detected in 167 out of 653 (25.6%) pregnant women. T. gondii B1 gene was identified in 36 out of 167 (21.6%) of IgG seropositive women. After delivery, the B1 gene was evaluated in 15 out of 36 (41.7%) patients' placental tissues, 13 of which were positive for this gene (86.7%). Anti- Toxoplasma IgM was detected neither in any umbilical cord nor in neonatal blood samples. All newborns, with the exception of one case, were born with normal birth weight and in term birth., Conclusion: The B1 gene was detected in 86.7% of the placental tissue of women who were involved in acute toxoplasmosis during pregnancy., Competing Interests: There are no conflicts of interest.