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Curcumin and its chalcone derivatives inhibit the growth of human cancer cells. It is reported that replacement of two OH groups in curcumin with less polar groups like methoxy increases its anti-proliferative activity. In this study, we explored benzylidine cyclohexanone derivatives with non-polar groups, to see if they possess increased anti-cancer activity. Novel 2,6-bis benzylidine cyclohexanone analogues of curcumin were synthesized, and their inhibitory effects on gastric adenocarcinoma (AGS) and esophageal squamous cell carcinoma (KYSE30) cancer cells were studied using an MTT assay. Cell apoptosis was detected by EB/AO staining, and cell cycle was analyzed by flow cytometry. Real-time PCR was performed for gene expression analysis. All synthesized analogues were cytotoxic toward gastric and esophageal cancer cells and showed lower IC 50 values than curcumin. Treatment with 2,6-Bis-(3-methoxy-4-propoxy-benzylidene)-cyclohexanone (BM2) was 17 times more toxic than curcumin after 48 h incubation. All novel compounds were more effective than curcumin in apoptosis induction and cell cycle arrest at G1 phase. These results suggest that less polar analogues of curcumin have potent cytotoxicity in vitro. However, they need to be investigated further, especially with animal tumor models, to confirm their chemotherapeutic activity in vivo.

We aimed to evaluate the expression of the major components of microRNA biogenesis machinery including Drosha, Dicer and DiGeorge syndrome critical region gene 8 (DGCR8) in multiple sclerosis (MS) patients. The expression levels of these components in relapsing remitting multiple sclerosis (RRMS) patients were significantly up-regulated in comparison to healthy controls. DGCR8 was up-regulated 4.9 times in RRMS patients versus healthy controls, and Drosha was up-regulated 3.58 times. Additionally, the expression level of Dicer was 2.11 times higher in RRMS patients than the healthy controls. In conclusion, our results suggest that overexpression of Drosha, Dicer and DGCR8 may contribute to the pathogenesis of MS. Further investigation may introduce microRNA biogenesis machinery as MS markers and therapeutic targets., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Esophageal cancer (EC) is a very common form of cancer in developing countries, and its exponential progression is a cause for concern. Available treatments face the phenomenon of multi-drug resistance, as well as multiple disabling side effects. The number of deaths is expected to double by 2030 if nothing is done. Due to their high representativeness in plants, phenolic compounds are a potential alternative for halting the spread of this disease, which bereaves many thousands of families every year. This study aims to identify phenolic compounds with activity against esophageal cancer, assess their toxicological profiles, and explore future perspectives. To achieve this, the literature search was meticulously carried out in the Google Scholar, Scopus, Web of Sciences, and Pub-Med/Medline databases, in accordance with the PRISMA 2020 guidelines. The results show that proanthocyanidin and curcumin represent promising therapeutic options, given their significant in vitro and in vivo activity, and their safety in human subjects in clinical trials. Moscatilin, Genistein, and pristimerin have anticancer activities (≤10 µM) very close to those of doxorubicin and 5-FU, although their safety has not yet been fully established. The compounds identified in vivo exhibit highly significant activities compared with the results obtained in vitro, and are sometimes more effective than the molecules conventionally used to treat EC. Generally, with the exceptions of plumbagin, lapachol, and β-lapachone, all other molecules are relatively non-toxic to normal human cells and represent a therapeutic avenue to be explored by pharmaceutical companies in the fight against esophageal cancer. However, more detailed toxicological studies of certain molecules remain a priority. [ABSTRACT FROM AUTHOR]

Unlabelled: MicroRNAs (miRNAs) have recently been shown to play fundamental roles in diverse cellular processes and linked to variety of cancers. Dicer and Drosha are two major enzymes in the miRNA maturation process. DGCR8 is the assistant of Drosha in the microprocessor complex. In this study, we evaluated the mRNA expression profiles of major miRNA processing machinery Drosha, Dicer, and DGCR8 in human gastrointestinal (AGS, KYSE30 and HepG2) cancer cell lines., Materials and Methods: The cells were cultured and harvested, and total cellular RNA was isolated from cells. Then, first-strand cDNA was synthesized from the RNA of cells. Afterward, Quantitative analysis was performed by real-time RT-PCR using the PowerSYBR Green PCR Master Mix., Results: Expression levels of Drosha in AGS and HepG2 cells were higher than the controls, whereas, Drosha's expression level in KYSE-30 cell line was lower. The Dicer expression levels in AGS and HepG2 cells were higher, while, its expression level in KYSE-30 cell was lower. The DGCR8 expression levels in all three cell lines were significantly higher than the control samples., Conclusion: Expression levels of the two most important enzymes of the miRNA machinery, Drosha and Dicer, and microprocessor complex component, DGCR8 were noticeably dysregulated when compared to healthy controls.

Background: This study investigated the effect of curcumin nanomicelle (CUR-n) on the structure of testis tissue, the process of spermatogenesis, LH, FSH, testosterone, and oxidative stress in a model of multiple sclerosis. Methods: Twenty-four male mice C57BL/6 were randomly allocated into 4 groups of 6 (1: group receiving 2% CPZ diet, 2: group receiving the diet of 2% CPZ + CUR-n with a dose of 50 mg/kg, 3: group receiving the diet of 2% CPZ + CUR-n with a dose of 100 mg/kg). The concentration of hormones (testosterone, LH and FSH), was measured by the special hormone assay ELISA kits. Measuring total antioxidant capacity (TAC) and Malondialdehyde (MDA) levels was done by spectrophotometry and calorimetric methods, respectively. Stereological analysis was done in order to explore the number of spermatogenesis cells, testis and sperm properties. Results: The results indicated that CUR-n (100 mg/kg) significantly enhanced the concentration of LH, FSH, testosterone, and TAC but reduced MDA levels. It also notably increased the quantity of spermatogonia, spermatocyte, round spermatids, long spermatids and LCs, augmented testis weight and volume, and germinal epithelium volume, improved sperm count, morphology, viability, and motility. In addition, a considerable decrease in the amount of wrinkling and disruption of the germinal epithelium was observed after intervention with CUR-n (100 mg/kg). Furthermore, a significant increase in the number of germ cells compared to the group receiving CPZ was detected. Conclusion: This study proposes that CUR-n could be a therapeutic agent for decreasing the adverse effects of MS on testis. [ABSTRACT FROM AUTHOR]

Background Gastric cancer (GC) is known as the fourth leading cause of cancer-related death and the fifth major cancer in the world, and this is a serious threat to general health all over the world. The lack of early detection markers results in a belated diagnosis, i.e. the final stages, which could be associated with the ineffectiveness of the treatment strategies, and naturally, it leads to poor prognosis. Even though a variety of treatments have been developed, there is a trend of studying traditional medicinal plants, due to the worrying side effect of drugs available in the market. Methods In this study, pharmacophore generation and 3D-QSAR model were created using 50 compounds with anti-gastric cancer activity (with IC50 had been reported in the previous studies). Results Based on three of the best pharmacophoric hypotheses, virtual screening was performed to discover the top antigastric cancer compounds from a database of 183,885 compounds. The selected compounds were used for molecular docking with three protein receptors 7BKG, 4F5B, and 4ZT1 to investigate the intermolecular interactions between these ligands and receptors. Finally, 21 lead compounds with the highest amount of docking score ranging from 13.366 to -6.404 kcal/ mol were selected, and then the ADME/Tox properties of these compounds were calculated. All these compounds have a fitness score above 1.8, a molecular weight of less than 500 g/mol, hydrogen bond donors up to 3, hydrogen bond acceptors up to 8.50, and logP of 1.013 to 4.174. Finally, molecular dynamic simulations for top-scoring ligand-receptor complexes were investigated. Conclusion These selected lead compounds have the most anti-gastric cancer effects among the 183,885 compounds in the database. Therefore, lead compounds might be considered for gastric cancer therapy in future studies. [ABSTRACT FROM AUTHOR]

Hypoxia can lead to different responses from cancer cells, including cell death or survival, partially depending on how long it is exposed. Patients with cancer and under hypoxic tumour conditions have a poorer prognosis and are at greater risk of metastasis. Physiological response to low oxygen levels is controlled by hypoxia-inducible factor (HIF)-1. Curcumin, the major component of the rhizomes of Curcuma longa L., reduces HIF-1 levels and function, inhibiting the production of vascular endothelial growth factor (VEGF). In addition, curcumin efficiently inhibits the angiogenesis of vascular endothelial cells triggered by hypoxia. One of the most compelling features that drive continued interest in curcumin is the molecules' modulation of initiation, promotion, and progression stages of cancer while concomitantly acting as a radiosensitizer and chemosensitizer for tumours. In this review, we discuss the role of curcumin in modulating hypoxia and investigate the mechanisms and regulatory factors of hypoxia in tumour tissues. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a central nervous system disease known for immune-mediated demyelination, inflammatory, and neurodegeneration symptoms. Discovering molecular biomarkers to classify RRMS and SPMS patients, monitor the disease activity, and response to particular treatments is one area that has received notable attraction. MicroRNA (miRNA), a single-stranded non-coding RNA molecule, is a significant regulator of gene expression recruited in pathogenic mechanisms in diverse diseases, especially cancer and MS. Also, the relapsing-remitting features of MS exhibit that both inflammatory and anti-inflammatory cytokines are effective in the progression of the disease over time. Methods and results: It was assessed the expression patterns of the genes (Drosha, Pasha (DGCR8), and Dicer) encoding the critical enzymes in the processing steps of miRNA maturation and major pro-inflammatory and anti-inflammatory cytokines (IFN-α, IFN-β, and IL-6) in blood cells of 40 MS patients (two groups of 10 men and women in both clinical courses of RR and SPMS patients) in comparison with 20 healthy control group (10 males and 10 females). The highest transcription activity of Drosha was observed for RRMS patients (4.2 and 3.6-fold, respectively), and the expression ratio was down regulated in male and female patients with SPMS (3.9- and 3.1-fold, respectively). Considering the studied cytokines, the increase in expression ratio of IL-6 in SPMS patients and the decrease in transcript abundance of INF-α, and INF-β cytokines are consistent with the progression of the disease. Conclusions: Our findings showed that the high and low transcriptional levels of the considered genes seem to be effective in the pathogenesis and progression of MS. [ABSTRACT FROM AUTHOR]

Background & Objective: Dicer a member of the RNase III endonucleases has a crucial function in the development of miRNAs that affects gene expression in different kinds of cancers. The present research focused on examining the expression level of Dicer and its relation with clinicopathological features in children with Acute Lymphoblastic Leukemia (ALL) among the population in the northwest region of Iran. Materials & Methods: In a case-control study, 140 samples (70 patients and 70 healthy controls of similar age and sex rates) from 2019 to 2021 were included in the Dicer mRNA expression levels assessment. Quantitative Real-Time PCR analyses were utilized to determine expression levels of Dicer in samples and the demographic and clinicopathologic features and the relationship of these variables were evaluated. Results: Average Dicer expression □ct values were 2.8267 and up-regulated compared to healthy samples (P=0.000). No significant relationships have been found among gene expression, demographical and clinicopathological parameters. Also, demographical and clinicopathological factors were not correlated with the mRNA expression level of the gene except age (r=0.148, P=0.001). Conclusion: The current research shows that the expression of Dicer is significantly upregulated in ALL patients, which suggests that it could have a vital function in ALL pathology. It will also theoretically be seen in the potential as a new intervention objective for ALL cases. [ABSTRACT FROM AUTHOR]

Cancer continues to cause an alarming number of deaths globally, and its burden on the health system is significant. Though different conventional therapeutic procedures are exploited for cancer treatment, the prevalence and death rates remain elevated. These, therefore, insinuate that novel and more efficient treatment procedures are needed for cancer. Curcumin, a bioactive, natural, phenolic compound isolated from the rhizome of the herbaceous plant turmeric, is receiving great interest for its exciting and broad pharmacological properties. Curcumin presents anticancer therapeutic capacities and can be utilized as a photosensitizing drug in cancer photodynamic therapy (PDT). Nonetheless, curcumin′s poor bioavailability and related pharmacokinetics limit its clinical utility in cancer treatment. This review looks at the physical and chemical properties, bioavailability, and safety of curcumin, while focusing on curcumin as an agent in cancer therapy and as a photosensitizer in cancer PDT. The possible mechanisms and cellular targets of curcumin in cancer therapy and PDT are highlighted. Furthermore, recent improvements in curcumin's bioavailability in cancer therapy using nanoformulations and delivery systems are presented. [ABSTRACT FROM AUTHOR]

On the basis of the urgent need to develop innovative and safe anticancer compounds, a series of chalcones, functionalized with various substituents in the aromatic portions and a long N-alkyl amide moiety, were designed and synthesized. The compatibility of novel compounds was firstly evaluated on non-tumoral human gingival fibroblasts (HGFs), secondly, the anti-proliferative effect on an adenocarcinoma gastric cell line (AGS) was measured. Among the chalcones, compound 3, at 50 µM after 48 and 72 h, showed, at the same time, an appreciable capability to counteract tumoral AGS viability and to preserve a high rate of healthy HGFs viability. Cell cycle analysis, performed on AGS cell line with 3 subtoxic dose (30 µM), suggested that the anti-proliferative effect could be related to a cell cycle arrest during the first stage and to an increase in the oxidative stress demonstrated by the significant augmentation of Reactive Oxygen Species release. Collectively, we have demonstrated that chalcone 3 had a potent anti-proliferative potential for the treatment of gastric adenocarcinoma and could be further investigated for new drug development. [ABSTRACT FROM AUTHOR]

Curcumin is a phenolic pigment, naturally present in Curcuma longa species. It is a yellow active ingredient and shows a pivotal role in the modulation of biological processes resulting in the prevention of cancer particularly due to its radical scavenging activities. In gastrointestinal cancer cells, curcumin has been shown to induce cell death through apoptosis and to cause cell cycle arrest, down-regulating glycolytic enzyme expressions alongside inhibition of the matrix metalloproteinase-2 (MMP-2) promoter activity and SDF-1α-induced cell invasion. It also activates the expression of cleaved caspase-3, reduces cell viability, regulates the ratio of Bcl-2/Bax, decreases the number of cells in the proliferative G0/G1 phase and increases the number of cells in the S phase. Additionally, curcumin prevents DNA from replication during the S phase. This review discusses the chemo-preventive role of curcumin and its mechanisms against human gastrointestinal cancers to understand its activity and potential utilization as a therapeutic moiety. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS), which leads to disturbances in the conduction of nerve impulses, cognitive impairment, sensory and motor disturbances, as well as depressive symptoms. MS remains an incurable disease with a difficult diagnosis and unclear etiology. The aim of the analysis was to identify SNPs that may potentially be associated with an increased risk of developing MS. Blood samples were obtained from patients with MS (194 subjects) and age-matched healthy controls (188 subjects). The polymorphic variant frequencies of rs197412 T>C in GEMIN3, rs7813 G>A in GEMIN4, rs1106042 G>A in HIWI, rs10719 A>C in DROSHA, rs3742330 A>G in DICER1, rs11077 T>G in XPO5, rs14035 C>T in RAN, rs636832 G>A in AGO1 were determined in DNA using real-time PCR TaqMan® SNP Genotyping Assay. Our findings indicate that the GG AGO1 rs636832 and AA GEMIN4 rs7813 genotypes were associated with an increased risk of MS. Although our findings provide a clearer understanding of the pathogenesis of MS, further investigations are needed to better understand their potential for the evaluation of other miRNA processing genes believed to be associated with MS etiology. [ABSTRACT FROM AUTHOR]

Cancer is still one of the most widespread diseases globally, it is considered a vital health challenge worldwide and one of the main barriers to long life expectancy. Due to the potential toxicity and lack of selectivity of conventional chemotherapeutic agents, discovering alternative treatments is a top priority. Plant-derived natural products have high potential in cancer treatment due to their multiple mechanisms of action, diversity in structure, availability in nature, and relatively low toxicity. In this review, the anticancer mechanisms of the most common phytochemicals were analyzed. Furthermore, a detailed discussion of the anticancer effect of combinations consisting of natural product or natural products with chemotherapeutic drugs was provided. This review should provide a strong platform for researchers and clinicians to improve basic and clinical research in the development of alternative anticancer medicines. [ABSTRACT FROM AUTHOR]

In cancer management, drug resistance remains a challenge that reduces the effectiveness of chemotherapy. Several studies have shown that curcumin resensitizes cancer cells to chemotherapeutic drugs to overcome resistance. In the present study, we investigate the potential therapeutic role of curcumin in regulating the proliferation of drug-resistant cancers. Six drug-sensitive (MCF7, HCT116, and A549) and -resistant (MCF7/TH, HCT116R, and A549/ADR) cancer cell lines were treated with curcumin followed by an analysis of cytotoxicity, LDH enzyme, total reactive oxygen species, antioxidant enzymes (SOD and CAT), fibrosis markers (TGF-β1 protein, fibronectin, and hydroxyproline), and expression of cellular apoptotic markers (Bcl-2, Bax, Bax/Bcl-2 ratio, Annexin V, cytochrome c, and caspase-8). Additionally, the expression of cellular SIRT1 was estimated by ELISA and RT-PCR analysis. Curcumin treatment at doses of 2.7–54.3 µM significantly reduced the growth of sensitive and resistant cells as supported with decreased viability and increased cellular LDH enzyme of treated cells compared to controls non-treated cells. Curcumin also at doses of 2.7 and 54.3 µM regulated the fibrogenesis by reducing the expression of fibrotic markers in treated cells. Analysis of apoptotic markers indicated increased Bax, Bax, Bax/Bcl-2 ratio, Annexin V, caspase-8, and cytochrome c expression, while Bcl-2 expressions were significantly reduced. In curcumin-treated cells at 2.7 μM, non-significant change in ROS with significant increase in SOD and CAT activity was observed, whereas an increase in ROS with a reduction in respective antioxidant enzymes were seen at higher concentrations along with significant upregulation of SIRT1. In conclusion, the present study shows that curcumin induces anticancer activity against resistant cancer cell lines in a concentration- and time-dependent manner. The protective activities of curcumin against the growth of cancer cells are mediated by modulating oxidative stress, regulating fibrosis, SIRT1 activation, and inducing cellular apoptosis. Therefore, curcumin could be tested as an auxiliary therapeutic agent to improve the prognosis in patients with resistant cancers. [ABSTRACT FROM AUTHOR]

Curcumin is a natural compound derived from turmeric and can target malignant tumor molecules involved in cancer propagation. It has potent antioxidant activity, but its effectiveness is limited due to poor absorption and rapid elimination from the body. Various curcumin derivatives have also shown anticancer potential in in-vitro and in-vivo models. Curcumin can target multiple signaling pathways involved in cancer development/progression or induce cancer cell death through apoptosis. In addition, curcumin and its derivatives could also enhance the effectiveness of conventional chemotherapy, radiation therapy and reduce their associated side effects. Lately, nanoparticle-based delivery systems are being developed/explored to overcome the challenges associated with curcumin's delivery, increasing its overall efficacy. The use of an imaging system to track these formulations could also give beneficial information about the bioavailability and distribution of the nano-curcumin complex. In conclusion, curcumin holds significant promise in the fight against cancer, especially in its nanoform, and could provide precise delivery to cancer cells without affecting normal healthy cells., (© 2023 John Wiley & Sons Ltd.)

Gastric carcinoma is one of the most prevalent malignancies and is associated with a high mortality. Chemotherapy is the principal therapeutic option in the treatment of gastric cancer, but its success rate is restricted by severe side effects and the prevalence of chemo-resistance. Curcumin is a polyphenolic compound derived from turmeric that has potent antioxidant, anti-inflammatory and anti-tumor effects. There is accumulating evidence that curcumin may prevent gastric cancer through regulation of oncogenic pathways. Furthermore some curcumin analogues and novel formulation of curcumin appear to have anti-tumor activity. The aim of this review was to give an overview of the therapeutic potential of curcumin and its derivatives against gastric cancer in preclinical and clinical studies. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) cancers with a high global prevalence are a leading cause of morbidity and mortality. Accordingly, there is a great need to develop efficient therapeutic approaches. Curcumin, a naturally occurring agent, is a promising compound with documented safety and anticancer activities. Recent studies have demonstrated the activity of curcumin in the prevention and treatment of different cancers. According to systematic studies on curcumin use in various diseases, it can be particularly effective in GI cancers because of its high bioavailability in the gastrointestinal tract. Nevertheless, the clinical applications of curcumin are largely limited because of its low solubility and low chemical stability in water. These limitations may be addressed by the use of relevant analogues or novel delivery systems. Herein, we summarize the pharmacological effects of curcumin against GI cancers. Moreover, we highlight the application of curcumin's analogues and novel delivery systems in the treatment of GI cancers. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is characterized by multifocal lesions, chronic inflammatory condition, and degenerative processes within the central nervous system (CNS) leading to demyelination. The most important cells involved in its pathogenesis are those which are CD4+, particularly proinflammatory Th1/Th17 and regulatory Treg. Signal cascades associated with CD4+ differentiation are regulated by microRNAs (miRNAs): short, single-stranded RNAs, responsible for negative regulation of gene expression at the posttranscriptional level. Several miRNAs have been consistently reported as showing dysregulated expression in MS, and their expression patterns may be elevated or decreased, depending on the function of specific miRNA in the immune system. Studies in MS patients indicate that, among others, miR-141, miR-200a, miR-155, miR-223, and miR-326 are upregulated, while miR-15b, miR-20b, miR-26a, and miR-30a are downregulated. Dysregulation of these miRNAs may contribute to the imbalance between pro- and anti-inflammatory processes, since their targets are associated with the regulation of Th1/Th17 and Treg cell differentiation. Highly expressed miRNAs can in turn suppress translation of key Th1/Th17 differentiation inhibitors. miRNA dysregulation may result from the impact of various factors at each stage of their biogenesis. Immature miRNA undergoes multistage transcriptional and posttranscriptional modifications; therefore, any protein involved in the processing of miRNAs can potentially lead to disturbances in their expression. Epigenetic modifications that have a direct impact on miRNA gene transcription may also play an important role. [ABSTRACT FROM AUTHOR]

Novel pyrrole derivatives were synthesized by one-pot four components condensation reaction of khellin and/or visnagin carbaldehyde; amine derivatives; curcumin and nitro methane. In another approach with lack of curcumin molecular structure, new pyrrole derivatives were efficiently achieved using ethyl acetoacetate. Newly synthesized compounds were tested against human pancreas cancer cell lines (Panc-1), colon cancer cell line and (MCF-7), (HT-29) breast cancer cell line. The results showed that newly synthesized compounds exhibit a moderate to strong growth inhibition of breast cancer cell line MCF-7 in comparison to the other two cell lines. Compounds which are combination between both Curcumin and khelline derivatives showed highest activity towards human breast cancer cell line (MCF-7). Molecular docking studies declared that these compounds occupied a pocket of "EGFR tyrosine kinase" (WT) and a pocket of "EGFAR Kinase domain PCSK9-∆C D374Y" (MT). In addition, our compounds are non-inhibitors of CYP2D6, which means that liver dysfunction effects are not expected. All newly synthesized strucrures are consistent with biological results and predicted to be safe. [ABSTRACT FROM AUTHOR]

Gastric precancerous lesions (GPLs) are an essential precursor in the occurrence and development of gastric cancer, known to be one of the most common and lethal cancers worldwide. Traditional Chinese medicine (TCM) has a positive prospect for the prevention and therapy of GPL owing to several advantages including a definite curative effect, fewer side effects compared to other treatments, multiple components, and holistic regulation. Despite these characteristic advantages, the mechanisms of TCM in treating GPL have not been fully elucidated. In this review, we summarize the current knowledge with respect to herbal formulations and the therapeutic mechanisms of TCM active ingredients for GPL. This paper elaborates on the mechanisms of TCM underlying the prevention and treatment of GPL, specifically those that are linked to anti-H. pylori, anti-inflammation, antiproliferation, proapoptotic, antioxidation, antiglycolytic, and antiangiogenesis effects. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is one if the common types of autoimmune disorders in developed countries. Various environmental and genetic factors are associated with initiation and progression of MS. It is believed that the life style changes can be one of the main environmental risk factors. The environmental factors are widely studied and reported, whereas minority of reports have considered the role of genetic factors in biology of MS. Although Iran is a low-risk country in the case of MS prevalence, it has been shown that there was a dramatically rising trend of MS prevalence among Iranian population during recent decades. Therefore, it is required to assess the probable MS risk factors in Iran. In the present study, we summarized all of the reported genes until now which have been associated with MS susceptibility among Iranian patients. To clarify the probable molecular biology of MS progression, we categorized these reported genes based on their cellular functions. This review paves the way of introducing a specific population-based diagnostic panel of genetic markers among the Iranian population for the first time in the world. [ABSTRACT FROM AUTHOR]

Chalcones represent precursor compounds for flavonoids biosynthesis in plants. Chalcones, 1,3-diaryl-2-propen-1-ones, have unique chemical structure with conjugated double bonds and delocalized π-electron system on both aromatic rings. Various studies have shown that chemical structure of chalcone is responsible for their antitumor effect. In our study, we have examined the antitumor effect of chalcone analogue (E) -1- (4-ethoxy-3-methoxyphenyl) -5-methylhex-1-en-3-one (CH) on HeLa cells. The antitumor efficiency of different CH concentrations was compared to the antitumor effects of dehydrozingerone and cisplatin. The viability of the cells was evaluated using MTT assay; type of the cell death was evaluated by Annexin V-FITC/7-AAD staining using FACS analysis; morphology changes of treated cells were visualized and compared to untreated cells using phase contrast microscopy. The result of our research showed that CH have a stronger antitumor compared to the effect both of dehydrozingerone and cisplatin. Our results indicated that chalcone analogue induced cell death via activation of apoptosis more powerfully compared to the apoptosis induced with dehydrozingerone and cisplatin. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the potential association between the genetic variants in miRNA processing genes (RAN, XPO5, DICER1 , and TARBP2) and susceptibility to type 2 diabetes mellitus (T2DM) and its vascular complications, as well as to further investigate their interaction with environmental factors in type 2 diabetes. Methods: We conducted a case-control study in genotyping of five polymorphic loci, including RAN rs14035, XPO5 rs11077, DICER1 rs13078, DICER1 rs3742330, and TARBP2 rs784567, in miRNA processing genes to explore the risk factors for T2DM and diabetic vascular complications. Haplotype analyses, interactions of gene-gene and interactions of gene-environment were performed too. Results: We identified a 36% decreased risk of developing T2DM in individuals with the minor A allele in DICER1 rs13078 (OR: 0.64; 95%CI: 0.42–0.95; P : 0.026). The AA haplotype in DICER1 was also associated with a protective effect on T2DM compared with the AT haplotype (OR: 0.63; 95%CI: 0.42–0.94; P -value: 0.023). T2DM patients with the TT+TC genotype at RAN rs14035 had a 1.89-fold higher risk of developing macrovascular complications than patients with the CC genotype (OR: 1.89; 95%CI: 1.04–3.45; P -value: 0.037). We also identified two three-factor interaction models. One is a three-factor [ DICER1 rs13078, body mass index (BMI), and triglyceride (TG)] interaction model for T2DM (OR: 5.93; 95%CI: 1.25–28.26; P = 0.025). Another three-factor [ RAN rs14035, hypertension (HP), and duration of T2DM (DOD)] interaction model was found for macrovascular complications of T2DM (OR = 41.60, 95%CI = 11.75–147.35, P < 0.001). Conclusion: Our study provides new evidence that two single nucleotide polymorphisms (SNPs) of the miRNA processing genes, DICER1 and RAN , and their interactions with certain environmental factors might contribute to the risk of T2DM and its vascular complications in the southern Chinese population. [ABSTRACT FROM AUTHOR]

Esophageal cancer is a common malignant tumor with an increasing trend during the past three decades. Currently, esophagectomy, often in combination with neoadjuvant chemo‐ and radiotherapy, is the cornerstone of curative treatment for esophageal cancer. However, esophagostomy is related to significant risks of perioperative mortality and morbidity, as well as lengthy recovery. Moreover, the adjuvant therapies including chemotherapy and radiotherapy are associated with numerous side effects, limiting compliance and outcome. The dietary agent curcumin has been extensively studied over the past few decades and is known to have many biological activities especially in regard to the prevention and potential treatment of cancer. This review summarizes the chemo‐preventive and chemotherapeutic potential of curcumin in esophageal cancer in both preclinical and clinical settings. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is among the most common malignancies in certain parts of the world, such as northwest Iran. miRNAs are small and single-stranded noncoding RNAs with about 19-23 nucleotides. Several studies have shown that miRNAs play important roles in gastric tumorigenesis. The aim of this study was to determine the effect of miRNA-1266-5p repression on the cell survival and alterations of the cell cycle in gastric cancer cell line of AGS (NCBI Code: C131, Gastric epithelial cell line). Methods: This experimental study was performed from April to December 2017 in Cellular-Molecular Research Center of Ardabil University of Medical Sciences, Iran. In this study, AGS cells were cultured in RPMI-1640 medium containing 10% serum and 1% antibiotic. The cells were transfected with miR-1266-5p mimic, miR-1266-5p inhibitor and HiPerFect reagent alone as negative control. The miR-1266-5p expression and transfection efficiency were analyzed by Stem-loop TaqMan qRT-PCR. The cell proliferation and cell cycle alterations were determined using MTT calorimetric assay and flow cytometry, respectively. The results were analyzed using SPSS 19.0 statistics software (SPSS Inc., Chicago, IL, USA) and presented as the means±standard deviation (SD). Results: miR-1266-5p expression was increased in AGS cells transfected with miR- 1266-5p mimic compared to control cells (P=0), while miR-1266-5p expression was decreased in transfected cells with the inhibitor compared to controls (P=0). Among different time points, the most effects of miR-1266-5p mimic and inhibitor were noticed after 48 hours of transfection. The upregulated miR-1266-5p significantly decreased cell growth, in contrast, inhibitor promoted cell proliferation (P=0). In addition, miR-1266-5p upregulation induced cell cycle arrest at the transition of G1 to S phase and led to G0/G1 entry (P=0), while of miR-1266-5p led to G2/M entry (P=0.001). Conclusion: According to the results obtained from this study, miR-1266-5p can reduce cell survival and induce cell cycle arrest and act as a tumor suppressor in AGS cells. While its inhibition can increase cell survival and reduce apoptosis. [ABSTRACT FROM AUTHOR]

Prion diseases are transmissible progressive neurodegenerative conditions characterized by rapid neuronal loss accompanied by a heterogeneous neuropathology, including spongiform degeneration, gliosis and protein aggregation. The pathogenic mechanisms and the origins of prion diseases remain unclear on the molecular level. Even though neurodegenerative diseases, including prion diseases, represent distinct entities, their pathogenesis shares a number of features including disturbed protein homeostasis, an overload of protein clearance pathways, the aggregation of pathological altered proteins, and the dysfunction and/or loss of specific neuronal populations. Recently, direct links have been established between neurodegenerative diseases and miRNA dysregulated patterns. miRNAs are a class of small non-coding RNAs involved in the fundamental post-transcriptional regulation of gene expression. Studies of miRNA alterations in the brain and body fluids in human prion diseases provide important insights into potential miRNA-associated disease mechanisms and biomarker candidates. miRNA alterations in prion disease models represent a unique tool to investigate the cause-consequence relationships of miRNA dysregulation in prion disease pathology, and to evaluate the use of miRNAs in diagnosis as biomarkers. Here, we provide an overview of studies on miRNA alterations in human prion diseases and relevant disease models, in relation to pertinent studies on other neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

The accumulation of mutated somatic cells due to the incompetency of body's immune system may lead to tumor onset. Therefore, enhancing the ability of the system to eliminate such cells should be the core of tumor therapy. The intrinsic antitumor immunity is triggered by tumorspecific antigens (TSA) or TSA-sensitized dendritic cells (DC). Once initiated, specific antitumor antibodies are produced and tumor-specific killer immune cells, including cytotoxic T lymphocytes (CTL), NK cells, and macrophages, are raised or induced. Several strategies may enhance antitumor action of immune system, such as supplying tumor-targeted antibody, activating T cells, enhancing the activity and tumor recognition of NK cells, promoting tumortargeted phagocytosis of macrophages, and eliminating the immunosuppressive myeloidderived suppressor cells (MDSCs) and Treg cells. Apart from the immune system, the removal of tumor burden still needs to be assisted by drugs, surgery or radiation. And the body's internal environment and tumor microenvironment should be improved to recover immune cell function and prevent tumor growth. Multiple microenvironment modulatory therapies may be applied, including addressing hypoxia and oxidative stress, correcting metabolic disorders, and controlling chronic inflammation. Finally, to cure tumor and prevent tumor recurrence, repairing or supporting therapy that consist of tissue repair and nutritional supplement should be applied properly. [ABSTRACT FROM AUTHOR]

Purpose: Despite advances in medical technology, radiation dermatitis occurs in 95% of patients receiving radiation therapy (RT) for cancer. Currently, there is no standard and effective treatment for the prevention or control of radiation dermatitis. The goal of the study was to determine the efficacy of oral curcumin, one of the biologically active components in turmeric, at reducing radiation dermatitis severity (RDS) at the end of RT, using the RDS scale, compared to placebo.Methods: This was a multisite, randomized, double-blinded, placebo-controlled trial of 686 breast cancer patients. Patients took four 500-mg capsules of placebo or curcumin three times daily throughout their prescribed course of RT until 1 week post-RT.Results: A total of 686 patients were included in the final analyses (87.5% white females, mean age = 58). Linear mixed-model analyses demonstrated that curcumin did not reduce radiation dermatitis severity at the end of RT compared to placebo (B (95% CI) = 0.044 (− 0.101, 0.188), p = 0.552). Fewer curcumin patients with RDS > 3.0 suggested a trend toward reduced severity (7.4 vs. 12.9%, p = 0.082). Patient-reported changes in pain, symptoms, and quality of life were not statistically significant between arms.Conclusions: Oral curcumin did not significantly reduce radiation dermatitis severity compared to placebo. The skin rating variation and broad eligibility criteria could not account for the undetectable therapeutic effect. An objective measure for radiation dermatitis severity and further exploration for an effective treatment for radiation dermatitis is warranted. [ABSTRACT FROM AUTHOR]

White matter injury (WMI) often results in cognitive impairment, behavioral disorders, and cerebral palsy and thus imposes a tremendous burden on society. The cells in brain white matter mainly comprise oligodendrocytes (OLs), astrocytes, and microglia. The dysregulation of OLs development is the pathological hallmark of WMI. Recent studies have demonstrated that microRNAs (miRNAs or miRs) participate in the regulation of OLs development, and the dysregulation of this process represents the pathogenesis of WMI. This review summarizes the progress made in this field that will help clinicians and researchers understand the molecular etiology of WMI and develop miRNAs as new agents for the prevention and treatment of WMI. [ABSTRACT FROM AUTHOR]

Breakthroughs in genetic studies, like whole human genome sequencing and genome-wide association studies (GWAS), have richened our knowledge of etiopathology of autoimmune diseases (AID) through discovery of genetic patterns. Nonetheless, the precise etiology of autoimmune diseases remains largely unknown. The lack of complete concordance of autoimmune disease in identical twins suggests that non-genetic factors also play a major role in determining disease susceptibility. Although there is no certain definition, epigenetics has been known as heritable alterations in gene function without changes in the nucleotide sequence. DNA methylation, histone modifications, and microRNA-associated gene expression suppression are the central mechanisms for epigenetic regulations. Multiple sclerosis (MS) is a disorder of the central nervous system (CNS), characterized by both inflammatory and neurodegenerative features. Although studies on epigenetic alterations in MS only began in the past decade, a mounting number of surveys suggest that epigenetic changes may be involved in the initiation and development of MS, probably through bridging the effects of environmental risk factors to genetics. Arming with clear understanding of epigenetic dysregulations underpins development of epigenetic therapies. Identifying agents inhibiting the enzymes controlling epigenetic modifications, particularly DNA methyltransferases and histone deacetylases, will be promising therapeutic tool toward MS. In the article underway, it is aimed to go through the recent progresses, attempting to disclose how epigenetics associates with the pathogenesis of MS and how can be used as therapeutic approach. [ABSTRACT FROM AUTHOR]

Malignant conditions of the gastrointestinal tract and accessory organs of digestion, including the oral cavity, esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus, are referred to as gastrointestinal cancers. Curcumin is a natural compound derived from turmeric with a wide range of biological activities. Several in vitro and in vivo studies have investigated the effects of curcumin on gastrointestinal cancers. In the current review, we aimed to provide an updated summary on the recent findings regarding the beneficial effects of curcumin on different gastrointestinal cancers in the recent decade. For this purpose, ScienceDirect," "Google Scholar," "PubMed," "ISI Web of Knowledge," and "Wiley Online Library" databases were searched using "curcumin", "cancer", and "gastrointestinal organs" as keywords. In vitro studies performed on different gastrointestinal cancerous cell lines have shown that curcumin can inhibit cell growth through cycle arrest at the G2/M and G1 phases, as well as stimulated apoptosis and autophagy by interacting with multiple molecular targets. In vivo studies performed in various animal models have confirmed mainly the chemopreventive effects of curcumin. Several nano-formulations have been proposed to improve the bioavailability of curcumin and increase its absorption. Moreover, curcumin has been used in combinations with many anti-tumor drugs to increase their anticarcinogenic properties. Taken together, curcumin falls within the category of plant-derived substances capable of preventing or treating gastrointestinal cancers. Further studies, particularly clinical trials, on the efficacy and safety of curcumin are suggested in this regard.

Acute lymphocytic leukemia (ALL) is one of the subtypes of leukemia; it is one of the leading causes of malignancy and morbidity and childhood mortality. This study examined the dysregulation of DROSHA and its clinical implications in ALL. In the case-control investigation, we have included 140 samples, consisting of 70 peripheral whole blood samples diagnosed with ALL and 70 age and sex-matched healthy children, to assess the level of expression of DROSHA mRNA between two groups. Quantitative Real-Time PCR was used to establish the level of DROSHA gene expression in the patients and controls. The results revealed that DROSHA was overexpressed in patients compared with controls (p < 0.001). There were no major differences between DROSHA expression and demographic factors and clinicopathological parameters (p > 0.001). The finding of the study revealed that DROSHA expression in ALL patients is significantly up-regulated; which is suggesting that may be served as a critical role in the pathogenesis of ALL. Also, DROSHA will possibly be utilized as a novel therapeutic target for ALL patients within the future.

MicroRNAs (miRNAs) directly and indirectly affect tumorigenesis.To be able to perform their myriad roles, miRNA machinery genes, such as Drosha, DGCR8, Dicer1, XPO5,TRBP, and AGO2, must generate precise miRNAs. These genes have specific expression patterns, protein-binding partners, and biochemical capabilities in different cancers. Our preliminary analysis of data from The Cancer Genome Atlas consortium on multiple types of cancer revealed significant alterations in these miRNA machinery genes. Here, we review their biological structures and functions with an eye toward understanding howthey could serve as cancer biomarkers. [ABSTRACT FROM AUTHOR]

Simple Summary: We provided an effective approach for the treatment of breast cancer as a malignant disease. Regards to this, we used drug delivery system. This approach does not have any side effects on the patients who suffer from cancer unlike chemotherapy, radiotherapy and drug resistance. This system implicates on using nano-drugs which loaded into nano-carrier. During this study, we used niosome@calcium alginate as a nano carrier which contained curcumin in aim of eradicating breast cancer cell lines. Through the research, we applied the above mentioned sample to breast cancer cell lines that were SKBR3 and MDA-MB231 and measured gene expression level to evaluate efficacy of this novel approach in therapy of this disease. Interestingly, applying curcumin loaded into niosome@calcium alginate in SKBR3 and MDA-MB231 as a treatment enhances cancer cell's death and apoptosis. We hope that this method could use as an effective and novel manner for the treatment of breast cancer. Cancer is one of the most common causes of mortality, and its various treatment methods can have many challenges for patients. As one of the most widely used cancer treatments, chemotherapy may result in diverse side effects. The lack of targeted drug delivery to tumor tissues can raise the possibility of damage to healthy tissues, with attendant dysfunction. In the present study, an optimum formulation of curcumin-loaded niosomes with a calcium alginate shell (AL-NioC) was developed and optimized by a three-level Box–Behnken design—in terms of dimension and drug loading efficiency. The niosomes were characterized by transmission electron microscopy, Fourier-transform infrared spectroscopy, and dynamic light scattering. The as-formulated niosomes showed excellent stability for up to 1 month at 4 °C. Additionally, the niosomal formulation demonstrated a pH-dependent release; a slow-release profile in physiological pH (7.4), and a more significant release rate at acidic conditions (pH = 3). Cytotoxicity studies showed high compatibility of AL-NioC toward normal MCF10A cells, while significant toxicity was observed in MDA-MB-231 and SKBR3 breast cancer cells. Gene expression studies of the cancer cells showed downregulation of Bcl2, cyclin D, and cyclin E genes, as well as upregulation of P53, Bax, caspase-3, and caspase-9 genes expression following the designed treatment. Flow cytometry studies confirmed a significant enhancement in the apoptosis rate in the presence of AL-NioC in both MDA-MB-231 and SKBR3 cells as compared to other samples. In general, the results of this study demonstrated that—thanks to its biocompatibility toward normal cells—the AL-NioC formulation can efficiently deliver hydrophobic drugs to target cancer cells while reducing side effects. [ABSTRACT FROM AUTHOR]

Gene expression dictates fundamental cellular processes and its de-regulation leads to pathological conditions. A key contributor to the fine-tuning of gene expression is Dicer, an RNA-binding protein (RBPs) that forms complexes and affects transcription by acting at the post-transcriptional level via the targeting of mRNAs by Dicer-produced small non-coding RNAs. This review aims to present the contribution of Dicer protein in a wide spectrum of human pathological conditions, including cancer, neurological, autoimmune, reproductive and cardiovascular diseases, as well as viral infections. Germline mutations of Dicer have been linked to Dicer1 syndrome, a rare genetic disorder that predisposes to the development of both benign and malignant tumors, but the exact correlation of Dicer protein expression within the different cancer types is unclear, and there are contradictions in the data. Downregulation of Dicer is related to Geographic atrophy (GA), a severe eye-disease that is a leading cause of blindness in industrialized countries, as well as to psychiatric and neurological diseases such as depression and Parkinson's disease, respectively. Both loss and upregulation of Dicer protein expression is implicated in severe autoimmune disorders, including psoriasis, ankylosing spondylitis, rheumatoid arthritis, multiple sclerosis and autoimmune thyroid diseases. Loss of Dicer contributes to cardiovascular diseases and causes defective germ cell differentiation and reproductive system abnormalities in both sexes. Dicer can also act as a strong antiviral with a crucial role in RNA-based antiviral immunity. In conclusion, Dicer is an essential enzyme for the maintenance of physiology due to its pivotal role in several cellular processes, and its loss or aberrant expression contributes to the development of severe human diseases. Further exploitation is required for the development of novel, more effective Dicer-based diagnostic and therapeutic strategies, with the goal of new clinical benefits and better quality of life for patients. [ABSTRACT FROM AUTHOR]

Cancer is the second leading cause of death in the world and one of the major public health problems. Despite the great advances in cancer therapy, the incidence and mortality rates of cancer remain high. Therefore, the quest for more efficient and less toxic cancer treatment strategies is still at the forefront of current research. Curcumin, the active ingredient of the Curcuma longa plant, has received great attention over the past two decades as an antioxidant, anti-inflammatory, and anticancer agent. In this review, a summary of the medicinal chemistry and pharmacology of curcumin and its derivatives in regard to anticancer activity, their main mechanisms of action, and cellular targets has been provided based on the literature data from the experimental and clinical evaluation of curcumin in cancer cell lines, animal models, and human subjects. In addition, the recent advances in the drug delivery systems for curcumin delivery to cancer cells have been highlighted. [ABSTRACT FROM AUTHOR]

A response is presented from the authors of the article "Strong reduction of AGO2 expression in melanoma and cellular consequences" that was published in a 2013 issue of the periodical.

A letter to the editor is presented in response to the article "Strong reduction of AGO2 expression in melanoma and cellular consequences" by D. Voller and colleagues that was published in the 2013 issue of the periodical.