Ag/g-C3N4 nanocomposite: Green fabrication and its application as a catalyst in the synthesis of new series of depsipeptides as biologically active compounds and investigation on their anti-breast cancer activity.

In this study, we bring forward a green and novel eco-friendly strategy for the fabrication of Ag/g-C3N4 nanocomposite via a fast in-situ generation method using Ferula Gummosa extracts as both stabilizer and reducing agent. Ag/g-C3N4 nanocomposite was analyzed by Fourier transform infrared spectra (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX-MAP), and transmission electron microscopy (TEM). After procurement and characterization, the catalytic activity of the prepared reagent was surveyed in the synthesis of a new series of depsipeptides using aspirin/ketoprofen, cyclohexyl isocyanide, and aryl aldehydes at ambient temperature in EtOH/H2O as a green media. Taking into account the economic and environmental facets, the method bestows some advantages such as using plant extracts as green media for the preparation of Ag nanoparticles, simple work-up procedure, mild reaction conditions, short reaction times, and high yields of the products. Additionally, the Ag/g-C3N4 nanocomposite catalyst can be recycled effectually and reused several times without a substantial loss in reactivity.

Evaluation of enterotoxigenic Bacteroides fragilis correlation with the expression of cellular signaling pathway genes in Iranian patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers all over the world, and dysbiosis in the gut microbiota may play a role in colorectal carcinogenesis. Bacteroides fragilis can lead to tumorigenesis by changing signaling pathways, including the WNT/ß-catenin pathway. Therefore, in the present study, we investigated the correlation between the enterotoxigenic B. fragilis amount and the expression of signaling pathway genes involved in CRC. MATERIALS AND METHODS: B. fragilis was determined in 30 tumors and adjacent healthy tissues by the qPCR method. Next, the relationship between enterotoxigenic B. fragilis and the expression of signaling pathway genes, including CCND1, TP53, BCL2, BAX, WNT, TCF, AXIN, APC, and CTNNB1 was investigated. Additionally, possible correlations between clinicopathological features of the tumor samples and the abundance of B. fragilis were analyzed. RESULTS: The results showed that B. fragilis was detected in 100% of tumor samples and 86% of healthy tissues. Additionally, enterotoxigenic B. fragilis colonized 47% of all samples, and bft-1 toxin was the most frequently found isotype among the samples. The analysis showed that the high level of B. fragilis has a significant relationship with the high expression of AXIN, CTNNB1, and BCL2 genes. On the other hand, our results did not show any possible correlation between this bacterium and the clinicopathological features of the tumor sample. CONCLUSION: B. fragilis had a higher abundance in the tumor samples than in healthy tissues, and this bacterium may lead to CRC by making changes in cellular signaling pathways and genes. Therefore, to better understand the physiological effects of B. fragilis on the inflammatory response and CRC, future research should focus on dissecting the molecular mechanisms by which this bacterium regulates cellular signaling pathways.

Synthesis, Biological Evaluation, and Molecular Modeling Studies of New 8-methyl-4-oxo-1,4-dihydroquinoline-3-carbohydrazides as Potential Anti-HIV Agents.

Background: The development of a highly safe and potent scaffold is a significant challenge in anti-HIV drug discovery. Objectives: This study aimed at developing a novel series of anti-HIV agents based on HIV integrase inhibitor pharmacophores. Methods: A novel series of 8-methyl-4-oxo-1,4-dihydroquinoline-3-carbohydrazide derivatives featuring various substituted benzoyl and N-phenyl carboxamide and carbothioamide moieties were designed and synthesized. Results: According to the biological evaluation, all the developed compounds were effective against HIV at concentrations lower than 150 µM, associated with no significant cytotoxicity (CC50 > 500 µM). Conclusions: Compound 8b, possessing a 4-fluorobenzoyl group, was the most potent compound, with an EC50 of 75 µM. Docking studies revealed that the binding modes of designed compounds are similar to the known HIV integrase inhibitors.

The Expression Levels of Circulating miR-129 and miR-203a in Association with Breast Cancer and Related Metastasis.

Background: A significant part of deaths related to breast cancer is the result of invasion to other organs. It is essential to discover new non-invasive biomarkers to improve anticipation of recurrence risk in breast cancer patients. In this study, the plasma levels of miR-129 and miR-203a were evaluated to investigate their diagnostic potential in breast cancer and its metastasis. Methods: In this case-control study, conducted in Tarbiat Modares University, Tehran, Iran, in 2019, Invasive Ductal Carcinoma blood samples were divided into 3 groups based on their stages as I, II/III, IV. Each group contained 30 individuals. We also recruited 30 normal individuals as a control group. Real-Time PCR was conducted to evaluate miR-129 and miR-203a expression levels. The discriminatory ability of the evaluated plasma miRNAs was assessed by ROC (Receiver Operating Characteristic) curves in breast cancer diagnosis and its metastasis. Results: MiR-129 and miR-203a expression levels were significantly downregulated in breast cancer. Reducing tendency was observed in the mentioned miRNAs from less to more invasive stages. The expression level of miR-129 was decreased in metastatic than non-metastatic patients and it was significantly related to metastasis. A significant association between miR-129 expression level and lymph node status was also observed (P=0.04). Evaluation of ROC curves revealed that miR-129 and miR-203a were able to discriminate breast cancer fairly and poorly respectively. The ability of miR-129 in the diagnosis of breast cancer metastasis was poor. Conclusion: MiR-129 and miR-203a may both act as tumor suppressor miRNAs. Our results need further evidence in a large population to be confirmed as diagnostic markers.

Assessment of DAPK1 and CAVIN3 Gene Promoter Methylation in Breast Invasive Ductal Carcinoma and Metastasis.

OBJECTIVE: Metastasis might be latent or occur several years after primary tumor removal. Currently used methods for detection of distant metastasis have still some limitations. Blood tests may improve sensitivity and specificity of currently used screening procedures. The present study was designed to investigate promoter methylation status of DAPK1 and CAVIN3 genes in plasma circulating free DNA (cfDNA) samples in Iranian invasive ductal carcinoma (IDC) patients. We also investigated association of two gene promoter methylations with breast cancer (BC) and metastatic BC was also assessed. MATERIALS AND METHODS: In this case-control study, MethySYBR assay was performed to determine DAPK1 and CAVIN3 promoter methylation status in breast IDC from 90 patients and 30 controls. Based on clinicopathological information, patient samples subdivided into stage I, II/III and IV groups (each group contained 30 individuals). RESULTS: According to the results an increased promoter methylation level of the DAPK1 gene in BC patients was observed. It was found that as disease progressed, the percentage of methylation was changed while it was not significant. Methylation changes in metastatic and non-metastatic BC revealed that methylation levels were significantly increased in metastatic than non-metastatic group. Analysis revealed that promoter methylation of CAVIN3 gene in BC patients was significantly increased. The observed methylation changes from less to more invasive stages were not significant in the CAVIN3 gene. Moreover, promoter methylation was changed in metastatic rather than non-metastatic condition, although it was not significant. CONCLUSION: Promoter hypermethylation of c and CAVIN3 genes in plasma are associated with the risk of BC and they can be potential diagnostic biomarkers along with current methods. Additionally, association of aberrant DAPK1 promoter methylation with metastasis suggests its potential usage as a non-invasive strategy for metastatic BC diagnosis.

An integrated analysis to predict micro-RNAs targeting both stemness and metastasis in human gastric cancer.

BACKGROUND AND AIM: Cancer stem cells (CSCs), a subpopulation of tumor cells, assess the capacity of self-renewal, metastasis, and therapeutic resistance. Regulation of CSCs and their epithelial to mesenchymal transition (EMT) potential is one of the promising strategies to eliminate cancer or to inhibit metastasis. Micro-RNAs (miRNAs) as regulators of several cell properties, such as self-renewal, metastasis, and resistance to the drug, could be proper targets in cancer diagnosis and therapy. The aim of the present study is to select common miRNAs targeting both self-renewal and metastasis in gastric cancer. METHODS: Stemness-related and EMT-related genes were selected by literature mining. The common miRNAs targeting genes were chosen using different databases and r programming language. The expression pattern of selected miRNAs and genes was evaluated in gastrospheres-as a gastric CSC model-and gastric tumor biopsies. RESULTS: Based on the integrated analysis, six miRNAs common to both stemness and metastasis were identified. miR-200c-3p and miR-520c-3p overexpressed in MKN-45 gastrospheres and grade III tumors. In AGS spheres, however, miR-520c-3p and miR-200c-3p upregulation and miR-34a-5p downregulation were similar to grade II tumors. Interestingly, miR-200c-3p and miR-520c-3p indicated a positive correlation with OCT4 and NOTCH1 expression in grade III tumors and MKN-45 spheres. Protein-protein network revealed that the EMT acquisition can be induced by stemness activation through intermediated core-regulatory genes, including CTNNB1, CTNND1, MAML1, KAT2A, and MAML3. CONCLUSION: The upregulation of mir-200c-3p and mir-520c-3p could effect on stemness and metastasis in gastric cancer as well as gastric CSCs. Therefore, they can be used as diagnosis and prognostic factors.

Fe3O4/g-C3N4 Nanocomposites as a Reusable Catalyst for the Synthesis of 5-Arylidenepyrimidine-2,4,6-(1H,3H,5H)-Trione and Pyrano-Pyrimidinone Derivatives in Aqueous Media.

A green magnetic nanocatalyst is developed by immobilization of Fe3O4 on Graphitic carbon nitride (g-C3N4) support for the efficacious synthesis of 5-arylidenepyrimidine-2,4,6-(1H,3H,5H)-trione and pyrano-pyrimidinone derivatives in aqueous media. The most momentous features of the present protocol are the simple preparation of the catalyst, mild reaction conditions, short reaction times and high yields of the products. Moreover, the magnetic nanocatalyst Fe3O4/g-C3N4 can be recycled effectively and reused several times, without a significant loss in reactivity.

GHSR DNA hypermethylation is a new epigenetic biomarker for gastric adenocarcinoma and beyond.

Aberrations of DNA methylation are early events in the development of tumors. In this study, we investigated the DNA methylation status of growth hormone secretagogue receptor (GHSR), a promising pan-cancer biomarker, in gastric cancer (GC). Initially, data sets from DNA methylation and gene expression studies available at Gene Expression Omnibus (GEO) were analyzed. Confirmation was done on primary tumor specimens and adjacent normal stomach tissue samples. Both analyses showed significant hypermethylation of GHSR. For further validation, The Cancer Genome Atlas data on stomach cancer was used. A receiver operating characteristic curve analysis yielded an area under the curve value of 0.85, corroborating its usefulness as a diagnostic marker. A genome-wide comethylation analysis revealed several correlated genes. CREB1 was found to act as an upstream regulator of this gene network. Furthermore, GHSR methylation was found to be a biomarker in several other tumor entities, namely cancers of the bladder, endometrium, esophagus, head and neck, liver, thyroid, kidney, and ovary. Our findings along with previous reports on other types of cancer suggest a high potential of GHSR gene methylation as a pan-cancer biomarker, which could be considered for liquid biopsy applications.

Epigenetic marks in estrogen receptor alpha CpG island correlate with some reproductive risk factors in breast cancer.

Reproductive backgrounds, such as age at menarche and menopause, age of first full-term pregnancy (FFTP), number of full-term deliveries and oral contraceptive use are main hormone-related risk factors of breast cancer. It seems that the mentioned factors may affect the risk of breast cancer by enhancing the duration of exposure to estrogen as a potent carcinogen for breast tissue, but the molecular mechanism which links each risk factor to breast cancer is unclear. Estrogen mainly works via its nuclear receptor (ERα). As epigenetic alterations such as CpG methylation are potential links between endogenous or exogenous exposures and genome, we hypothesized that hormone-related risk factors may correlate with the epigenetic marks of the ERα promoter in breast tumors. In the present study, the CpG methylation status of the ERα gene in 99 samples of breast tumors belonged to women with different reproductive histories was evaluated. The reproductive history data were collected from patients. ERα CpG methylation was investigated by methylation specific PCR in DNA samples were obtained from the breast tumors. We could show that some of the hormone-related risk factors (early FFTP and increased number of pregnancies) were inversely correlated with epigenetic marks in ERα gene in breast tumors. Other hormone-related risk factors such as age of menarche and menopause and oral contraceptive use did not show any association with ERα methylation. It seems that pregnancy-related risk factors in comparison with other hormone-related factors work via different mechanism. As ERα methylation is a poor prognosis marker in breast tumors, its association with some modifiable reproductive risk factors (FFTP age and numbers of pregnancies) reiterates the importance of programming reproductive life style not only for prevention of breast cancer but also in favoring the prognosis of the affected women. The exact molecular mechanisms of the observed correlation need more investigation in the future.

The chemokine receptor CXCR4 is associated with the staging of gastric cancer.

BACKGROUND: CXCR4 is a cognitive receptor for stromal-derived factor-1 (SDF-1) and has been previously shown to be associated with tumor growth and invasion of many cancers. However, its expression and function in gastric cancer has not been well clarified. MATERIALS AND METHODS: Herein, we studied the expression of CXCR4 on gastric samples from patients with gastric adenocarcinoma in comparison with precancerous lesions by employing qRT-PCR. RESULTS: Our qRT-PCR data show that CXCR4 is highly expressed in tissue samples from patients with gastric cancer than precancerous lesions (2.4 times higher, P value < 0.05). When we correlated the level of CXCR4 with clinicopathological findings, we observed that CXCR4 level is associated with staging of the disease and lymphatic invasion. IN CONCLUSION: We present evidence that CXCR4 level is significantly elevated in later stages of gastric cancer. Thus, CXCR4 may play a crucial role in gastric cancer progression.