Innovating Cancer Treatment Through Cell Cycle, Telomerase, Angiogenesis, and Metastasis.

Cancer remains a formidable challenge in the field of medicine, necessitating innovative therapeutic strategies to combat its relentless progression. The cell cycle, a tightly regulated process governing cell growth and division, plays a pivotal role in cancer development. Dysregulation of the cell cycle allows cancer cells to proliferate uncontrollably. Therapeutic interventions designed to disrupt the cell cycle offer promise in restraining tumor growth and progression. Telomerase, an enzyme responsible for maintaining telomere length, is often overactive in cancer cells, conferring them with immortality. Targeting telomerase presents an opportunity to limit the replicative potential of cancer cells and hinder tumor growth. Angiogenesis, the formation of new blood vessels, is essential for tumor growth and metastasis. Strategies aimed at inhibiting angiogenesis seek to deprive tumors of their vital blood supply, thereby impeding their progression. Metastasis, the spread of cancer cells from the primary tumor to distant sites, is a major challenge in cancer therapy. Research efforts are focused on understanding the underlying mechanisms of metastasis and developing interventions to disrupt this deadly process. This review provides a glimpse into the multifaceted approach to cancer therapy, addressing critical aspects of cancer biology-cell cycle regulation, telomerase activity, angiogenesis, and metastasis. Through ongoing research and innovative strategies, the field of oncology continues to advance, offering new hope for improved treatment outcomes and enhanced quality of life for cancer patients.

The critical role of circular RNAs in drug resistance in gastrointestinal cancers.

Nowadays, drug resistance (DR) in gastrointestinal (GI) cancers, as the main reason for cancer-related mortality worldwide, has become a serious problem in the management of patients. Several mechanisms have been proposed for resistance to anticancer drugs, including altered transport and metabolism of drugs, mutation of drug targets, altered DNA repair system, inhibited apoptosis and autophagy, cancer stem cells, tumor heterogeneity, and epithelial-mesenchymal transition. Compelling evidence has revealed that genetic and epigenetic factors are strongly linked to DR. Non-coding RNA (ncRNA) interferences are the most crucial epigenetic alterations explored so far, and among these ncRNAs, circular RNAs (circRNAs) are the most emerging members known to have unique properties. Due to the absence of 5' and 3' ends in these novel RNAs, the two ends are covalently bonded together and are generated from pre-mRNA in a process known as back-splicing, which makes them more stable than other RNAs. As far as the unique structure and function of circRNAs is concerned, they are implicated in proliferation, migration, invasion, angiogenesis, metastasis, and DR. A clear understanding of the molecular mechanisms responsible for circRNAs-mediated DR in the GI cancers will open a new window to the management of GI cancers. Hence, in the present review, we will describe briefly the biogenesis, multiple features, and different biological functions of circRNAs. Then, we will summarize current mechanisms of DR, and finally, discuss molecular mechanisms through which circRNAs regulate DR development in esophageal cancer, pancreatic cancer, gastric cancer, colorectal cancer, and hepatocellular carcinoma.

Oncostatic activities of melatonin: Roles in cell cycle, apoptosis, and autophagy.

Melatonin, the major secretory product of the pineal gland, not only regulates circadian rhythms, mood, and sleep but also has actions in neoplastic processes which are being intensively investigated. Melatonin is a promising molecule which considered a differentiating agent in some cancer cells at both physiological and pharmacological concentrations. It can also reduce invasive and metastatic status through receptors MT1 and MT2 cytosolic binding sites, including calmodulin and quinone reductase II enzyme, and nuclear receptors related to orphan members of the superfamily RZR/ROR. Melatonin exerts oncostatic functions in numerous human malignancies. An increasing number of studies report that melatonin reduces the invasiveness of several human cancers such as prostate cancer, breast cancer, liver cancer, oral cancer, lung cancer, ovarian cancer, etc. Moreover, melatonin's oncostatic activities are exerted through different biological processes including antiproliferative actions, stimulation of anti-cancer immunity, modulation of the cell cycle, apoptosis, autophagy, the modulation of oncogene expression, and via antiangiogenic effects. This review focuses on the oncostatic activities of melatonin that targeted cell cycle control, with special attention to its modulatory effects on the key regulators of the cell cycle, apoptosis, and telomerase activity.

MicroRNAs and osteosarcoma: Potential targets for inhibiting metastasis and increasing chemosensitivity.

Osteosarcoma (OS) is the third most common cancer in young adults after lymphoma and brain cancer. Metastasis, like other cellular events, is dependent on signaling pathways; a series of changes in some proteins and signaling pathways pave the way for OS cells to invade and migrate. Ezrin, TGF-ß, Notch, RUNX2, matrix metalloproteinases (MMPs), Wnt/ß-catenin, and phosphoinositide 3-kinase (PI3K)/AKT are among the most important of these proteins and signaling pathways. Despite the improvements in treating OS, the overall survival of patients suffering from the metastatic disease has not experienced any significant change after surgical treatments and chemotherapy and 5-years overall survival in patients with metastatic OS is about 20%. Studies have shown that overexpression or inhibition of some microRNAs (miRNAs) has significant effects in limiting the invasion and migration of OS cells. The results of these studies highlight the potential of the clinical application of some miRNA mimics and miRNA inhibitors (antagomiRs) to inhibit OS metastasis in the future. In addition, some studies have shown that miRNAs are associated with the most important drug resistance mechanisms in OS, and some miRNAs are highly effective targets to increase chemosensitivity. The results of these studies suggest that miRNA mimics and antagomiRs may be helpful to increase the efficacy of conventional chemotherapy drugs in the treatment of metastatic OS. In this article, we discussed the role of various signaling pathways and the involved miRNAs in the metastasis of OS, attempting to provide a comprehensive review of the literature on OS metastasis and chemosensitivity.

The Interaction Network of MicroRNAs with Cytokines and Signaling Pathways in Allergic Asthma.

Allergic asthma is a complicated disease that is affected by many factors. Numerous cytokines and signaling pathways are attributed to the cause of asthma symptoms. MicroRNAs (miRNAs) are a group of small non-coding single-stranded RNA molecules that are involved in gene silencing and posttranscriptional regulation of gene expression by targeting mRNAs. In pathological conditions, altered expression of microRNAs differentially regulates cytokines and signaling pathways and therefore, can be the underlying reason for the pathogenesis of allergic asthma. Indeed, microRNAs participate in airway inflammation via inducing airway structural cells and activating immune responses by targeting cytokines and signaling pathways. Thus, to make a complete understanding of allergic asthma, it is necessary to investigate the communication network of microRNAs with cytokines and signaling pathways which is contributed to the pathogenesis of allergic asthma. Here, we shed light on this aspect of asthma pathology by Summarizing our current knowledge of this topic.

Oncostatic activities of melatonin: Roles in cell cycle, apoptosis, and autophagy.

Melatonin, the major secretory product of the pineal gland, not only regulates circadian rhythms, mood, and sleep but also has actions in neoplastic processes which are being intensively investigated. Melatonin is a promising molecule which considered a differentiating agent in some cancer cells at both physiological and pharmacological concentrations. It can also reduce invasive and metastatic status through receptors MT1 and MT2 cytosolic binding sites, including calmodulin and quinone reductase II enzyme, and nuclear receptors related to orphan members of the superfamily RZR/ROR. Melatonin exerts oncostatic functions in numerous human malignancies. An increasing number of studies report that melatonin reduces the invasiveness of several human cancers such as prostate cancer, breast cancer, liver cancer, oral cancer, lung cancer, ovarian cancer, etc. Moreover, melatonin's oncostatic activities are exerted through different biological processes including antiproliferative actions, stimulation of anti-cancer immunity, modulation of the cell cycle, apoptosis, autophagy, the modulation of oncogene expression, and via antiangiogenic effects. This review focuses on the oncostatic activities of melatonin that targeted cell cycle control, with special attention to its modulatory effects on the key regulators of the cell cycle, apoptosis, and telomerase activity.

Assessment of mucin and alpha-amylase levels in gingival crevicular fluid of chronic periodontitis patients.

BACKGROUND: Chronic periodontitis is the most common form of periodontitis. Several immune and inflammatory factors responsible for periodontal destruction have been found in gingival crevicular fluid (GCF). The current study was conducted to determine the correlation between mucin and alpha-amylase protein values in GCF with chronic periodontitis. METHOD: Forty-five patients with moderate-to-severe chronic periodontitis were selected. Samples of GCF were taken from a specific part of a single root tooth and placed in a closed test tube containing phosphate-buffered saline (PBS) (pH = 7). Sampling was done again after one month. Pre- and post-treatment samples were analyzed for measuring the levels of mucin and alpha-amylase proteins. RESULTS: Paired t test results for these two variables showed that the difference between mucin and alpha-amylase levels before and after treatment is significant. CONCLUSION: The level of both mucin and alpha-amylase in GCF in patients with chronic periodontitis was higher than that of patients who have recovered successfully; and evaluating the values of these two markers could be used to determine the activity of the periodontal disease.

Evaluation of Fructosamine 3-kinase and Glyoxalase 1 activity in normal and breast cancer tissues.

BACKGROUND: Breast cancer is a typical malignancy and the most common in the female and it is the primary reason behind cancer-related deaths of women around the world. The pathological role of the non-enzymatic change of proteins by reducing sugars become frequently shows in different kinds of cancer. Cancer cells generally rely upon aerobic glycolysis as the main source of energy. Impaired glucose metabolism is somewhat responsible for the aggregation of advanced glycation end products (AGEs). Methylglyoxal (MG), a glycolysis byproduct either contributes to the accumulation of AGEs. Enzymatic defense upon AGEs products exists in all mammalian cells. AIMS: The present work intends to look into Glyoxalase1 (GLO1) and fructosamine-3-kinase (FN3K) activity in human breast carcinoma. METHODS: Thirty-three consecutive patients were entered into the study. Samples of breast tumoral tissue and normal matches were drawn from patients after surgery. FN3K and GLO1 enzymatic activity were analyzed using a radiometric and spectrophotometric assay. RESULTS: The average level of FN3K enzyme was fundamentally lower in cancerous tissues parallel with adjacent noncancerous tissues. We also observed a consistent increase of GLO1 activity in the tumor parallel with pair-matched normal tissue. CONCLUSION: The current findings build up a key-role of enzymatic defense to detoxify cytotoxic AGEs and methylglyoxal levels in tumor cells. These discoveries may give another system to the treatment of breast cancer.

NORAD, a critical long non-coding RNA in human cancers.

The incidence of cancer is growing worldwide, and it is becoming the most common cause of death. Long non-coding RNAs (lncRNAs) are a group of RNA transcripts with a length larger than 200 nucleotides that cannot encode proteins or peptides. LncRNAs regulate different biological functions by controlling gene expressions at transcriptional, translational, and post-translational levels. Non-coding RNA activated by DNA damage (NORAD) is a highly conserved lncRNA necessary for genome stability. LncRNA NORAD is dysregulated in various types of cancers. This biomarker has been involved in numerous processes associated with carcinogeneses, such as cell proliferation, apoptosis, invasion, and metastasis. In this paper, we reviewed the role of lncRNA NORAD and its biological functions in various human cancers to provide future research insights.

The regulatory functions of circular RNAs in osteosarcoma.

Osteosarcoma (OS) is known as a malignant bone tumor affecting mainly children and younger adults. Despite all the improvements in the treatment of OS, the overall survival among patients remained mostly unsatisfied. It involves different mechanisms and signaling pathways. Some recent studies confirmed that circular RNAs (circRNAs) have a revelatory role in controlling OS cell proliferation, invasion, and metastasis. CircRNAs consist of a covalently closed-loop structure with neither 5' nor 3' poly adenylated tail, lacking protein-encoding ability formed by back-splicing mechanisms. They mainly act as microRNA (miRNA) sponges and modulate the downstream biological processes. Up/down regulation of some circRNAs demonstrated to serve as the oncogenic factor in some tumor tissues such as OS. In this article, we review the regulatory functions of circRNAs resulting in OS cell progression or restraint and the potential for being used in vitro or in vivo as diagnostic or therapeutic biomarkers.

CRISPR/Cas9 gene editing: A new therapeutic approach in the treatment of infection and autoimmunity.

CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein9) may be viewed as an adaptive bacterial immune system. When a virus infects a bacterium, a fragment of the virus genome is inserted into the CRISPR sequence of the bacterial genome as a memory. When the bacterium becomes infected again with the same virus, an RNA molecule that is a transcript of the memory sequence, directs Cas9, an endonuclease, to the complementary region of the virus genome, and Cas9 disables the virus by a double-strand break. In recent years, studies have shown that by designing synthetic RNA molecules and delivering them along with Cas9 into eukaryotic cells, different regions of the cell's genome can be targeted and manipulated. These findings have drawn much attention to this new technology and it has been shown that CRISPR/Cas9 gene editing can be used to treat some human diseases. These include infectious diseases and autoimmune diseases. In this review article, in addition to a brief overview of the biology of the CRISPR/Cas9 system, we collected the most recent findings on the applications of CRISPR/Cas9 technology for better investigation of the pathogenesis and treatment of viral infections (human immunodeficiency virus infection, hepatitis virus infections, and onco-virus infections), non-viral infections (parasitic, fungal, and bacterial infections), and autoimmune diseases.

Comparison of the calcium-related factors in Parkinson's disease patients with healthy individuals.

BACKGROUND: Parkinson's disease (PD) is one of the most common neurodegenerative diseases (ND). Studies have demonstrated that biochemical markers have an association with PD. We aimed to investigate an association of biochemical markers including calcium, vitamin D, alkaline phosphatase (ALP), parathormone (PTH), and phosphorous with PD. METHODS: This study was conducted on 139 PD patients and 100 healthy individuals. Serum levels of calcium, phosphorous, ALP, PTH and vitamin D were evaluated. Furthermore, student's t-test and logistic regression models were used by SPSS. RESULTS: The mean levels of calcium (9.4±0.7 and 9.0±0.8 ) and vitamin D (29.7±22.1 and 25.8±23.7) were higher in PD patients as compared with healthy controls, which only status of calcium being significantly different in the two groups (P<0.001). Levels of ALP (202.4±96.7 and 242.9±142.4) and phosphorous (3.6±0.6 and 4.22±1.1) were significantly different comparing PD patients with healthy subjects (P<0.01, P<0.001, respectively). ALP and phosphorous were significantly different in the two groups (OR=0.996, [CI 95%, 0.994-0.999], P<0.001, OR=0.475, [CI 95%, 0.325-0.694], P<0.001, respectively). Furthermore, increased levels of calcium resulted in an elevated risk of PD (OR=2.175, [CI 95% 1.377-3.435], P<0.001). CONCLUSION: Results show that mean levels of calcium are higher in PD patients relative to healthy controls. Thereby, higher levels of calcium may be associated with PD.

Critical roles of long noncoding RNAs in breast cancer.

Breast cancer is a major clinical challenge that affects a wide range of the female population and heavily burdens the health system. In the past few decades, attempts have been made to understand the etiology of breast cancer, possible environmental risk factors, and the genetic predispositions, pathogenesis, and molecular aberrations involved in the process. Studies have shown that breast cancer is a heterogeneous entity; each subtype has its specific set of aberrations in different cell signaling pathways, such as Notch, Wnt/ß-catenin, transforming growth factor-ß, and mitogen-activated protein kinase pathways. One novel group of molecules that have been shown to be inducted in the regulation of multiple cell signaling pathways is the long noncoding RNAs (lncRNAs). These molecules have important implications in the regulation of multiple signaling pathways by interacting with various genes, affecting the transcription process, and finally, playing roles in posttranslational control of these genes. There is growing evidence that lncRNAs are involved in the process of breast cancer formation by effecting the aforementioned signaling pathways, and that this involvement can have significant diagnostic and prognostic values in clinical contexts. The present review aims to elicit the significance of lncRNAs in the regulation of cell signaling pathways, and the resulting changes in cell survival, proliferation, and invasion, which are the hallmarks of breast cancer.

MicroRNAs in breast cancer: Roles, functions, and mechanism of actions.

Breast cancer is one of the most lethal malignancies in women in the world. Various factors are involved in the development and promotion of the malignancy; most of them involve changes in the expression of certain genes, such as microRNAs (miRNAs). MiRNAs can regulate signaling pathways negatively or positively, thereby affecting tumorigenesis and various aspects of cancer progression, particularly breast cancer. Besides, accumulating data demonstrated that miRNAs are a novel tool for prognosis and diagnosis of breast cancer patients. Herein, we will review the roles of these RNA molecules in several important signaling pathways, such as transforming growth factor, Wnt, Notch, nuclear factor-κ B, phosphoinositide-3-kinase/Akt, and extracellular-signal-regulated kinase/mitogen activated protein kinase signaling pathways in breast cancer.

The interplay of Klotho with signaling pathway and microRNAs in cancers.

Klotho (KL) gene has been accepted as an "aging suppressor" gene that encodes a single transmembrane protein in human known as Klotho which is commonly expressed in renal tubes. The interruption in the secretion of Klotho protein expedites aging whereas its high expression extends lifespan. The family of Klotho proteins has been reported to act as distinct receptors for endocrine fibroblast growth factors (FGFs), which manage multifarious metabolic processes. Further, the secreted Klotho is a hormonal factor that takes part in the ion channel organization. Numerous studies determined that this protein affects the function of a number of important signaling pathways, which may present an impact in tumorigenesis via the coordination of receptors located on them. This review article focuses on the effects of microRNAs on the performance of Klotho and how the interplay between Klotho and certain pathways like insulin-like growth factor, FGF, Wnt, and transforming growth factor ß contribute to the biogenesis of cancer. The present study is also pointed at defining the molecular mechanisms of these interactions.

New insights into the role of microRNAs and long noncoding RNAs in most common neurodegenerative diseases.

Neurodegenerative diseases (NDs) are a diversity of neurological disorders characterized by the progressive degeneration of the structure and function of the central nervous system (CNS). The most common NDs are Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Recently, many studies have investigated associations between common NDs with noncoding RNAs (ncRNAs) molecules. ncRNAs are regulatory molecules in the normal functioning of the CNS. Two of the most important ncRNAs are microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). These types of ncRNAs are involved in different biological processes including brain development, maturation, differentiation, neuronal cell specification, neurogenesis, and neurotransmission. Increasing data has demonstrated that miRNAs and lncRNAs have strong correlations with the development of NDs, particularly gene expression. Besides, ncRNAs can be introduced as new biomarkers for diagnosis and prognosis of NDs. Hence, in this review, we summarized the involvement of various miRNAs and lncRNAs in most common NDs followed by a correlation of ncRNAs dysregulation with the AD, PD, and HD.

The crosstalk between trace elements with DNA damage response, repair, and oxidative stress in cancer.

DNA damage response (DDR) is a regulatory system responsible for maintaining genome integrity and stability, which can sense and transduce DNA damage signals. The severity of damage appears to determine DDRs, which can include damage repair, cell-cycle arrest, and apoptosis. Furthermore, defective components in DNA damage and repair machinery are an underlying cause for the development and progression of various types of cancers. Increasing evidence indicates that there is an association between trace elements and DDR/repair mechanisms. In fact, trace elements seem to affect mediators of DDR. Besides, it has been revealed that oxidative stress (OS) and trace elements are associated with cancer development. In this review, we discuss the role of some critical trace elements in the risk of cancer. In addition, we provide a brief introduction on DDR and OS in cancer. Finally, we will further review the interactions between some important trace elements including selenium, zinc, chromium, cadmium, and arsenic, and DDR, and OS in cancer.