Interaction between lncRNAs and RNA-binding proteins (RBPs) influences DNA damage response in cancer chemoresistance.

The DNA damage response (DDR) is a crucial cellular signaling pathway activated in response to DNA damage, including damage caused by chemotherapy. Chemoresistance, which refers to the resistance of cancer cells to the effects of chemotherapy, poses a significant challenge in cancer treatment. Understanding the relationship between DDR and chemoresistance is vital for devising strategies to overcome this resistance and improve treatment outcomes. Long non-coding RNAs (lncRNAs) are a class of RNA molecules that do not code for proteins but play important roles in various biological processes, including cancer development and chemoresistance. RNA-binding proteins (RBPs) are a group of proteins that bind to RNA molecules and regulate their functions. The interaction between lncRNAs and RBPs has been found to regulate gene expression at the post-transcriptional level, thereby influencing various cellular processes, including DDR signaling pathways. Multiple studies have demonstrated that lncRNAs can interact with RBPs to modulate the expression of genes involved in cancer chemoresistance by impacting DDR signaling pathways. Conversely, RBPs can regulate the expression and function of lncRNAs involved in DDR. Exploring these interactions can provide valuable insights for the development of innovative therapeutic approaches to overcome chemoresistance in cancer patients. This review article aims to summarize recent research on the interaction between lncRNAs and RBPs during cancer chemotherapy, with a specific focus on DDR pathways.

Autophagy-targeted nanoparticles in breast carcinoma: A systematic review.

Breast cancer is a commonly known cancer type and the leading cause of cancer death among females. One of the unresolved problems in cancer treatment is the increased resistance of the tumor to existing treatments, which is a direct result of apoptotic defects. Calculating an alternative to cell death (autophagy) may be the ultimate solution to maximizing cancer cell death. Our aim in this study was to investigate the potential of free nanoparticles (un-drug-loaded) in the induction or inhibition of autophagy and consider this effect on the therapy process. When the studies met the inclusion criteria, the full texts of all relevant articles were carefully examined and classified. Of the 25 articles included in the analysis, carried out on MCF-7, MDA-MB-231, MDA-MB-231-TXSA, MDA-MB-468, SUM1315, and 4T1 cell lines. Twenty in vitro studies and five in vivo/in vitro studies applied five different autophagy tests: Acridine orange, western blot, Cyto-ID Autophagy Detection Kit, confocal microscope, and quantitative polymerase chain reaction. Nanoparticles (NPs) in the basic format, including Ag, Au, Y2 O3 , Se, ZnO, CuO, Al, Fe, vanadium pentoxide, and liposomes, were prepared in the included articles. Three behaviors of NPs related to autophagy were seen: induction, inhibition, and no action. Screened and presented data suggest that most of the involved free NPs (metallic NPs) in this systematic review had reactive oxygen species-mediated pathways with autophagy induction (36%). Also, PI3K/Akt/mTOR and MAPK/ERK signaling pathways were mentioned in just four studies (16%). An impressive percentage of studies (31%) did not examine the NP-related autophagy pathway.

MicroRNAs and Periodontal Disease: Helpful Therapeutic Targets?

Periodontal disease is the most common oral disease. This disease can be considered as an inflammatory disease. The immune response to bacteria accumulated in the gum line plays a key role in the pathogenesis of periodontal disease. In addition to immune cells, periodontal ligament cells and gingival epithelial cells are also involved in the pathogenesis of this disease. miRNAs which are small RNA molecules with around 22 nucleotides have a considerable relationship with the immune system affecting a wide range of immunological events. These small molecules are also in relation with periodontium tissues especially periodontal ligament cells. Extensive studies have been performed in recent years on the role of miRNAs in the pathogenesis of periodontal disease. In this review paper, we have reviewed the results of these studies and discussed the role of miRNAs in the immunopathogenesis of periodontal disease comprehensively. miRNAs play an important role in the pathogenesis of periodontal disease and maybe helpful therapeutic targets for the treatment of periodontal disease.

Synthesis, characterization, and evaluation of pH-sensitive doxorubicin-loaded functionalized graphene oxide in osteosarcoma cells.

Introduction: Doxorubicin (DOX) is one of the most common drugs in cancer treatment. However, its partial solubility along with the high incidence of side effects remains a challenge to tackle. To address these issues, we designed a formulation based on graphene oxide (GO) and used it as an anticancer drug delivery system. Methods: The physical and chemical properties of the formulation were studied using FTIR, SEM, EDX, Mapping, and XRD. Release studies in the in vitro condition were used to evaluate the pH sensitivity of drug release from nanocarriers. Other in vitro studies, including uptake assay, MTT, and apoptosis assay were carried out on the osteosarcoma cell line. Results: in vitro release studies confirmed that the synthesized formulation provides a better payload release profile in acidic conditions, which is usually the case in the tumor site. On the OS cell line, the cytotoxicity of the DOX-loaded nanocarrier (IC50=0.293 µg/mL) and early apoptosis rate (33.80 % ) were higher in comparison to free DOX (IC50=0.472 µg/mL, and early apoptosis rate= 8.31 % ) after 48 hours. Conclusion: In summary, our results suggest a DOX-loaded graphene oxide carrier as a potential platform for targeting cancer cells.

Applications of engineered exosomes in drugging noncoding RNAs for cancer therapy.

Noncoding RNAs (ncRNAs) are engaged in key cell biological and pathological events, and their expression alteration is connected to cancer progression both directly and indirectly. A huge number of studies have mentioned the significant role of ncRNAs in cancer prevention and therapy that make them an interesting subject for cancer therapy. However, there are several limitations, including delivery, uptake, and short half-life, in the application of ncRNAs in cancer treatment. Exosomes are introduced as promising options for the delivery of ncRNAs to the target cells. In this review, we will briefly discuss the application and barriers of ncRNAs. After that we will focus on exosome-based ncRNAs delivery and their advantages as well as the latest achievements in drugging ncRNAs with exosomes.

Multiple function of lncRNA MALAT1 in cancer occurrence and progression.

Long non-coding RNAs (lncRNAs) have received particular attention in the last decade due to its engaging in carcinogenesis and tumorigenesis. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a lncRNA that plays physiological and pathological roles in many aspects of genome function as well as biological processes involved in cell development, differentiation, proliferation, invasion, and migration. In this article, we will review the effects of lncRNA MALAT1 on the progression of six prevalent human cancers by focusing on MALAT1 ability to regulate post-transcriptional modification and signaling pathways.

Vitamin D in respiratory viral infections: a key immune modulator?

Respiratory viral infections are common respiratory diseases. Influenza viruses, RSV and SARS-COV2 have the potential to cause severe respiratory infections. Numerous studies have shown that unregulated immune response to these viruses can cause excessive inflammation and tissue damage. Therefore, regulating the antiviral immune response in the respiratory tract is of importance. In this regard, recent years studies have emphasized the importance of vitamin D in respiratory viral infections. Although, the most well-known role of vitamin D is to regulate the metabolism of phosphorus and calcium, it has been shown that this vitamin has other important functions. One of these functions is immune regulation. Vitamin D can regulate the antiviral immune response in the respiratory tract in order to provide an effective defense against respiratory viral infections and prevention from excessive inflammatory response and tissue damage. In addition, this vitamin has preventive effects against respiratory viral infections. Some studies during the COVID-19 pandemic have shown that vitamin D deficiency may be associated with a higher risk of mortality and sever disease in patients with COVID-19. Since, more attention has recently been focused on vitamin D. In this article, after a brief overview of the antiviral immune response in the respiratory system, we will review the role of vitamin D in regulating the antiviral immune response comprehensively. Then we will discuss the importance of this vitamin in influenza, RSV, and COVID-19.

Role of exosomal miRNA in chemotherapy resistance of Colorectal cancer: A systematic review.

The third most common malignancy has been identified as Colorectal cancer (CRC) that conducive to death in most cases. Chemoresistance is a common obstacle to CRC treatment. Circulating exosomal microRNAs (miRNAs) have been shown to reverse chemo-resistance and are promising biomarkers for CRC. The capacity of engineered exosomes to cross biological barriers and deliver functional miRNAs could be used to achieve these proposes. The object of this review is the investigation of the role of exosomal miRNA in the chemo-resistance, diagnosis, and prognosis of CRC. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, electronic databases, PubMed, EMBASE, Web of Science, Scopus were searched from January 1990 to November 2020. Ultimately, eight articles included five in vitro (16 cell lines) and three in vivo examinations. Three studies demonstrated that increasing or decreasing mRNA expression was associated with increasing and decreasing cell proliferation in vitro. The presence of miRNA in two studies increased the sensitivity of the drug and exhibited a considerable growth inhibitory effect on cancer cell proliferation. The apoptotic rate was significantly increased in four studies by increased mRNA expression and reduced mrna expression. Tumor volume of xenograft models in three studies suppressed by antitumor miRNA activity. In contrast, anti-miRNA activity in one study decreased the tumor volume. Exosomal miRNAs can be regulators of chemo-resistance and predict adverse outcomes in CRC patients. In sum, exosomes containing miRNAs can be a promising biomarker for the prognosis and diagnosis of CRC. Subsequent research should be a focus on delineating the function of exosomal miRNA before clinical use.

Melatonin and inflammatory bowel disease: From basic mechanisms to clinical application.

Inflammatory bowel disease is a chronic inflammatory disease and has periods of recurrence and remission. Improper immune responses to gut flora bacteria, along with genetic susceptibility, appear to be involved in causing this complex disease. It seems dysbiosis and oxidative stress may also be involved in IBD pathogenesis. A significant number of clinical studies have shown an interesting association between sleep disturbances and IBD. Studies in animal models have also shown that sleep deprivation has a significant effect on the pathogenesis of IBD and can aggravate inflammation. These interesting findings have drawn attention to melatonin, a sleep-related hormone. Melatonin is mainly produced by the pineal gland, but many tissues in the body, including the intestines, can produce it. Melatonin can have an interesting effect on the pathogenesis of IBD. Melatonin can enhance the intestinal mucosal barrier, alter the composition of intestinal bacteria in favor of bacteria with anti-inflammatory properties, regulate the immune response, alleviate inflammation and attenuate oxidative stress. It seems that, melatonin supplementation is effective in relieving inflammation and healing intestinal ulcers in IBD animal models. Some clinical studies have also shown that melatonin supplementation as an adjuvant therapy may be helpful in reducing disease activity in IBD patients. In this review article, in addition to reviewing the effects of sleep disturbances and melatonin on key mechanisms involved in the pathogenesis of IBD, we will review the findings of clinical studies regarding the effects of melatonin supplementation on IBD treatment.

Long noncoding RNA SNHG7-miRNA-mRNA axes crosstalk with oncogenic signaling pathways in human cancers.

LncRNAs and miRNAs are the two most important non-coding RNAs, which have been identified to be associated with cancer progression or prevention. The dysregulation of lncRNAs conducts tumorigenesis and metastasis in different ways. One of the mechanisms is that lncRNAs interact with miRNAs to regulate distinct cellular and genomic processes and cancer progression. LncRNA SNHG7 as an oncogene sponges miRNAs and develops lncRNA-miRNA-mRNA axes, leading to the regulation of several signaling pathways such as Wnt/ß-Catenin, PI3K/AKT/mTOR, SIRT1, and Snail-EMT. Therefore, in this article, after a brief overview of lncRNA SNHG7-miRNA-mRNA axes' contribution to cancer development, we will discuss the role of lncRNA SNHG7 in the genes expression and signaling pathways related to cancers development via acting as a ceRNA.

Polyphenols and inflammatory bowel disease: Natural products with therapeutic effects?

Inflammatory bowel disease (IBD) is a long-life disease with periods of recurrence and relief. Oxidative stress plays an important role in the pathogenesis of this disease. Recent years' studies in the field of IBD treatment mostly have focused on targeting cytokines and immune cell trafficking using antibodies and inhibitors, altering the composition of intestinal bacteria in the line of attenuation of inflammation using probiotics and prebiotics, and attenuating oxidative stress through antioxidant supplementation. Studies in animal models of IBD have shown that some polyphenolic compounds including curcumin, quercetin, resveratrol, naringenin, and epigallocatechin-3-gallate can affect almost all of the above aspects and are useful compounds in the treatment of IBD. Clinical studies performed on IBD patients have also confirmed the findings of animal model studies and have shown that supplementation with some of the above-mentioned polyphenolic compounds has positive effects in reducing disease clinical and endoscopic activity, inducing and maintaining remission, and improving quality of life. In this review article, in addition to a detailed reviewing the effects of the above-mentioned polyphenolic compounds on the events involved in the pathogenesis of IBD, the results of these clinical studies will also be reviewed.

The modulatory effects of two bioflavonoids, quercetin and thymoquinone on the expression levels of DNA damage and repair genes in human breast, lung and prostate cancer cell lines.

BACKGROUND: The recent decade has witnessed the increasing potential of various flavonoids such as quercetin and thymoquinone in inhibiting cancer cells proliferation and growth and their therapeutic effects in various cancers. Therefore, in the current study, we aim to evaluate the expression levels of key factors of DNA damage response in human breast, lung and prostate cancer cell lines in response to treatment with quercetin and thymoquinone. METHODS: MTT assay was applied to assess the effects of quercetin and thymoquinone on the viability of MCF-7, A549, and PC3 cancer cells. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to evaluate the expression levels of p53, RAD51, Ku70, XRCC1, and H2AX in treated cells. In addition, the expression rate of 8-hydroxy-deoxyguanosine (8-OH-dG) was assessed by ELISA kit. RESULTS: The quercetin and thymoquinone induce cytotoxicity in breast, lung, and prostate cancer cells effectively; MCF-7 cells were the most sensitive cells to quercetin with an IC50 value of 50 µM and PC3 cells were more sensitive to thymoquinone with an IC50 value of 20 µM. The expression levels of DNA damage markers, H2AX, and 8-OH-dG were significantly increased in all cancer cells treated with quercetin and thymoquinone (p < 0.05). Moreover, both flavonoids significantly decreased the expression levels of DNA repair mediators, RAD51, Ku70, XRCC1, in cell lines. P53 was also increased in MCF-7 and A549 cells. CONCLUSION: We concluded that quercetin and thymoquinone may exert their effects through modulation of DNA damage response, increasing DNA damage, and suppressing DNA repair genes.

The role of melatonin in bone regeneration: A review of involved signaling pathways.

Increasing bone resorption followed by decreasing bone mineralization are hallmarks of bone degeneration, which mostly occurs in the elderly population and post-menopausal women. The use of mesenchymal stem cells (MSCs) has raised many promises in the field of bone regeneration due to their high osteoblastic differentiation capacity and easy availability from abundant sources. A variety of compounds, including growth factors, cytokines, and other internal factors, have been combined with MSCs to increase their osteoblastic differentiation capacity. One of these factors is melatonin, whose possible regulatory role in bone metabolism and formation has recently been suggested by many studies. Melatonin also is a potential signaling molecule and can affect many of the signaling pathways involved in MSCs osteoblastic differentiation, such as activation of PI3K/AKT, BMP/Smad, MAPK, NFkB, Nrf2/HO-1, Wnt, SIRT/SOD, PERK/ATF4. Furthermore, melatonin in combination with other components such as strontium, vitamin D3, and vitamin K2 has a synergistic effect on bone microstructure and improves bone mineral density (BMD). In this review article, we aim to summarize the regulatory mechanisms of melatonin in osteoblastic differentiation of MSCs and underling involved signaling pathways as well as the clinical potential of using melatonin in bone degenerative disorders.

CRISPR/Cas9 gene editing: a new approach for overcoming drug resistance in cancer.

The CRISPR/Cas9 system is an RNA-based adaptive immune system in bacteria and archaea. Various studies have shown that it is possible to target a wide range of human genes and treat some human diseases, including cancers, by the CRISPR/Cas9 system. In fact, CRISPR/Cas9 gene editing is one of the most efficient genome manipulation techniques. Studies have shown that CRISPR/Cas9 technology, in addition to having the potential to be used as a new therapeutic approach in the treatment of cancers, can also be used to enhance the effectiveness of existing treatments. Undoubtedly, the issue of drug resistance is one of the main obstacles in the treatment of cancers. Cancer cells resist anticancer drugs by a variety of mechanisms, such as enhancing anticancer drugs efflux, enhancing DNA repair, enhancing stemness, and attenuating apoptosis. Mutations in some proteins of different cellular signaling pathways are associated with these events and drug resistance. Recent studies have shown that the CRISPR/Cas9 technique can be used to target important genes involved in these mechanisms, thereby increasing the effectiveness of anticancer drugs. In this review article, studies related to the applications of this technique in overcoming drug resistance in cancer cells will be reviewed. In addition, we will give a brief overview of the limitations of the CRISP/Cas9 gene-editing technique.

Melatonin Increases the Sensitivity of Osteosarcoma Cells to Chemotherapy Drug Cisplatin.

Chemotherapy, which is one of the common treatments for osteosarcoma (OS), has many side effects and in some cases has low effectiveness due to chemoresistance, hence it is vital to study new therapies for OS. In this regard, we combined melatonin with cisplatin and evaluate their effect on MG63 OS cells. Since melatonin has anti-cancer properties, we hypothesized that its combination with cisplatin could increase the effectiveness of cisplatin. Firstly, MTT assay was used to evaluate the cell viability and cytotoxicity of cisplatin on MG63 cells and the results showed that melatonin in combination with cisplatin increases the sensitivity of MG63 cells to cisplatin. In addition, qRT-PCR results showed that the expressions of miR-181 and P53, CYLD, CBX7 and BCL2 genes change in MG63 cells after treatment with the combination of cisplatin and melatonin, so that the expression of P53, CYLD and CBX7 increased and the expression of BCL2 and miR-181b decreases significantly. Furthermore, analysis of Annexin V/FITC assay data revealed that the rate of apoptosis in MG63 OS cell line remarkably promoted after treated with cisplatin and melatonin combination. As a result, our findings show that melatonin in combination with cisplatin increases the effectiveness of cisplatin in osteosarcoma cells and this study provides a new therapeutic approach for OS.

DNA repair and damage pathways in mesothelioma development and therapy.

Malignant mesothelioma (MMe) is an aggressive neoplasm that occurs through the transformation of mesothelial cells. Asbestos exposure is the main risk factor for MMe carcinogenesis. Other important etiologies for MMe development include DNA damage, over-activation of survival signaling pathways, and failure of DNA damage response (DDR). In this review article, first, we will describe the most important signaling pathways that contribute to MMe development and their interaction with DDR. Then, the contribution of DDR failure in MMe progression will be discussed. Finally, we will review the latest MMe therapeutic strategies that target the DDR pathway.

DNA damage response signaling pathways as important targets for combination therapy and chemotherapy sensitization in osteosarcoma.

Osteosarcoma (OS) is the most common bone malignancy that occurs most often in young adults, and adolescents with a survival rate of 20% in its advanced stages. Nowadays, increasing the effectiveness of common treatments used in OS has become one of the main problems for clinicians due to cancer cells becoming resistant to chemotherapy. One of the most important mechanisms of resistance to chemotherapy is through increasing the ability of DNA repair because most chemotherapy drugs damage the DNA of cancer cells. DNA damage response (DDR) is a signal transduction pathway involved in preserving the genome stability upon exposure to endogenous and exogenous DNA-damaging factors such as chemotherapy agents. There is evidence that the suppression of DDR may reduce chemoresistance and increase the effectiveness of chemotherapy in OS. In this review, we aim to summarize these studies to better understand the role of DDR in OS chemoresistance in pursuit of overcoming the obstacles to the success of chemotherapy.

Quercetin and Methotrexate in Combination have Anticancer Activity in Osteosarcoma Cells and Repress Oncogenic MicroRNA-223.

INTRODUCTION: Osteosarcoma (OS) is one of the most common bone neoplasms in adolescents. Notable short- and long-term toxic effects of OS chemotherapy regimens have been reported. Hence, new chemotherapeutic agents with the ability to potentiate OS chemotherapy drugs and protect non-tumorous tissues are required. METHODS: Saos-2 cells were treated with Methotrexate (MTX) and Quercetin (Que) (a polyphenolic flavonoid with anti-tumor effects) alone and in combination. MTT assay was performed to investigate the cytotoxicity of the drugs. Moreover, apoptosis-involved genes, including miR-223, p53, BCL-2, CBX7, and CYLD expression were analyzed via qRT-PCR. Annexin V-FITC/PI kit was employed to assess the apoptosis rate. RESULTS: The MTT results showed that Que increases MTX cytotoxicity on OS cells. The measured IC50s are 142.3 µM for QUE and 13.7 ng/ml for MTX. A decline in MTX IC50 value was observed from 13.7 ng/ml to 8.45 ng/ml in the presence of Que. Moreover, the mRNA expression outcomes indicated that the combination therapy significantly up-regulates the tumor suppressor genes, such as p53, CBX7, and CYLD, and declines anti-apoptotic genes BCL-2 and miR-223, which can lead to proliferation inhibition and apoptosis inducement. Furthermore, the apoptosis rate increased significantly from 6.03% in the control group to 38.35% in Saos-2 cells that were treated with the combination of MTX and Que. CONCLUSION: Que, with the potential to boost the anticancer activity of MTX on Saos-2 cancer cells through proliferation inhibition and apoptosis induction, is a good candidate for combination therapy.

From inflammatory bowel disease to colorectal cancer: what's the role of miRNAs?

Inflammatory Bowel Disease (IBD) is a chronic inflammatory disease with relapse and remission periods. Ulcerative colitis and Crohn's disease are two major forms of the disease. IBD imposes a lot of sufferings on the patient and has many consequences; however, the most important is the increased risk of colorectal cancer, especially in patients with Ulcerative colitis. This risk is increased with increasing the duration of disease, thus preventing the progression of IBD to cancer is very important. Therefore, it is necessary to know the details of events contributed to the progression of IBD to cancer. In recent years, the importance of miRNAs as small molecules with 20-22 nucleotides has been recognized in pathophysiology of many diseases, in which IBD and colorectal cancer have not been excluded. As a result, the effectiveness of these small molecules as therapeutic target is hopefully confirmed. This paper has reviewed the related studies and findings about the role of miRNAs in the course of events that promote the progression of IBD to colorectal carcinoma, as well as a review about the effectiveness of some of these miRNAs as therapeutic targets.

The Effect of TQ and Cis in OS.

INTRODUCTION: Osteosarcoma (OS) is a primary bone sarcoma with a high recurrence rate and poorer prognosis. The application of natural agents in combinational therapies can increase the efficacy of treatment and decrease the side effects. Herein, we aimed to evaluate the effects of Thymoquinone (TQ) combined with Cisplatin on apoptosis and its underlying mechanisms in the Saos-2 cells. METHODS: The effects of TQ and Cisplatin on Saos-2 cell viability were measured using an MTT assay. Western blotting was applied for the measurement of γH2AX protein expression. The expression levels of 8-Hydroxy-2'-deoxyguanosine (8-oxo-dG) were evaluated by enzyme-linked immunosorbent assay (ELISA). DCFH-DA fluorescence dye was used to detect reactive oxygen species (ROS) formation. For evaluation of apoptosis, flow cytometry was employed. RESULTS: TQ dramatically promotes the cytotoxic effects of Cisplatin. TQ considerably enhanced the expression levels of 8-oxo-dG and γ-H2AX in Saos-2 cells. After TQ treatment, ROS levels were increased; furthermore, TQ treatment resulted in the potentiation of Cisplatin-induced apoptosis in Saos-2 cells compared to either TQ or Cisplatin treated cells. CONCLUSION: In general, TQ plus Cisplatin resulted in potentiated cellular cytotoxicity by increasing ROS level and inducing oxidative DNA damage, leading to the potent induction of apoptosis in tumor cells.