The emerging role of miR-200 family in metastasis: focus on EMT,CSCs, angiogenesis,and anoikis

Introduction

Cancer is the second major threat to human society and one of the main challenges facing healthcare systems. One of the main problems of cancer care is the metastases of cancer cells that cause 90% of deaths due to cancer. Multiple molecular mechanisms are involved in cancer cell metastasis. Therefore, a better understanding of these molecular mechanisms is necessary for designing restrictive strategies against cancer cell metastasis. Accumulating data suggests that MicroRNAs (miRNAs) are involved in metastasis and invasion of human tumors through regulating multiple genes expression levels that are involved in molecular mechanisms of metastasis. The goal of this review is to present the molecular pathways by which the miR 200 family manifests its effects on EMT, cancer stem cells, angiogenesis, anoikis, and the effects of tumor cell metastases.

Methods

A detailed literature search was conducted to find information about the role of the miR-200 family in the processes involved in metastasis in various databases.

Results

Numerous lines of evidence revealed an association between the mir-200 family and metastasis of human tumors by impressing processes such as cancer stem cells, EMT, angiogenesis, and anoikis.

Conclusions

Understanding the molecular mechanisms associated with metastasis in which the miR-200 family is involved can be effective in treating metastatic cancers.

Graphic abstract

     

Hybrid nanoreservoirs based on dextran-capped dendritic mesoporous silica nanoparticles for CD133-targeted drug delivery

In this study, the chemical features of dendritic mesoporous silica nanoparticles (DMSNs) provided the opportunity to design a nanostructure with the capability to intelligently transport the payload to the tumor cells. In this regard, doxorubicin (DOX)-encapsulated DMSNs was electrostatically surface-coated with polycarboxylic acid dextran (PCAD) to provide biocompatible dextran-capped DMSNs (PCAD-DMSN@DOX) with controlled pH-dependent drug release. Moreover, a RNA aptamer against a cancer stem cell (CSC) marker, CD133 was covalently attached to the carboxyl groups of DEX to produce a CD133-PCAD-DMSN@DOX. Then, the fabricated nanosystem was utilized to efficiently deliver DOX to CD133+ colorectal cancer cells (HT29). The in vitro evaluation in terms of cellular uptake and cytotoxicity demonstrated that the CD133-PCAD-DMSN@DOX specifically targets HT29 as a CD133 overexpressed cancer cells confirmed by flow cytometry and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. The potentially promising intelligent-targeted platform suggests that targeted dextran-capped DMSNs may find impressive application in cancer therapy.     

Relative shifts in mobility in anionic peroxidase isoenzymes between stem base and apex of flax genotrophs

Anionic peroxidase isoenzymes, separated on acrylamide gels, were examined in two flax genotrophs and in their reciprocal F₂ hybrids. Isoenzyme 1 exhibited a significant difference in R_m between stem base and apex and there was a gradient of decreasing R_m and activity between base and apex. Isoenzyme 2 displayed only the activity gradient. The parents differed significantly in the R_m's and activities of isoenzymes 1 and 2, and the F₂'s showed complete dominance of the L parent for R_m, with activities being approximately intermediate.     

HPV16-E7 Protein T Cell Epitope Prediction and Global Therapeutic Peptide Vaccine Design Based on Human Leukocyte Antigen Frequency: An In-Silico Study

International Journal of Peptide Research and Therapeutics - Cervical cancer is the second most common leading cause of women's death due to cancer worldwide, about 528,000 patients’...     

Hepatitis C virus genotypes in patients with chronic hepatitis C infection in southern Iran from 2016 to 2019

Hepatitis C is a liver disease caused by the hepatitis C virus (HCV). The treatment of HCV infection has become more complicated due to various genotypes and subtypes of HCV. The treatment of HCV has made significant advances with direct-acting antivirals. However, for the choice of medicine or the combination of drugs for hepatitis C, it is imperative to detect and discriminate the crucial HCV genotypes. The main objective of this study was to determine the pattern of circulating HCV genotypes in southern Iran, from 2016 until 2019. The other aim of the study was to determine possible associations of patients’ risk factors with HCV genotypes. A total of 803 serum samples were collected in 4 years (2016–2019) from patients with HCV antibody positive results. A total of 728 serum samples were HCV-RNA positive. The prevalence of HCV genotypes was detected using the genotype-specific RT-PCR test for serum samples obtained from 615 patients. The HCV genotype 1 (G1) was the most prevalent (48.8%) genotype in the area, with G1a, G1b, and mixed G1a/b representing 38.4%, 10.1%, and 0.3%, respectively. Genotype 3a was the next most prevalent (47.2%). Mixed genotypes 1a/3a were detected in 22 (3.6%) and finally G4 was found in 3 (0.5%) patients. The other HCV genotypes were not detected in any patient. Genotype 1 (1a and 1b alone, 1a/1b and 1a/3a coinfections) is the most prevalent HCV genotype in southern Iran. HCV G1 shows a significantly higher rate in people under 40 years old.     

Application of Bacillus pumilus as a potential biocontrol agent of Fusarium wilt of tomato

The current study aimed at evaluating the possibility of native Bacillus pumilus species to control Fusarium wilt in tomato and examine its effect on plant growth. Biocontrol traits of B. pumilus strains, biofilm assay, root colonisation and in vivo studies under pot conditions were determined. Strain ToIrMA-KC806242 formed biofilm efficiently and could colonise and survive on tomato rhizosphere (3.1 × 10⁴ CFU/g of root). The amount of auxin production was recorded 29.7 μg/ml at the 96th hour of incubation. Siderophore production was determined positive, while ToIrMA was not able to solubilise phosphate compounds or produce cyanide hydrogen. Statistical analysis of data revealed that the increase in root and shoot length was recorded 60 and 84%, respectively, over control. In addition, about 73% reduction in disease incidence was determined in vivo experiments. In conclusion, this study suggests B. pumilus ToIrMA strain as a possible biocontrol agent in the field experiments.     

Knowledge,Attitudes and Perceptions of Saudis towards Participating in Clinical Trials

Aim

To assess the knowledge, attitudes, and perceptions of Saudis towards participating in clinical trials (CTs).

Methods

A cross-sectional study was conducted on 232 Saudi adult patients and their companions visiting adult outpatient clinics at King Fahad Medical City, Riyadh, Saudi Arabia. Data were collected using a self-administered questionnaire based on information obtained from the literature. The questionnaire was divided into four sections, one covering the respondents’ demographics, and the other three assessing knowledge, attitudes, and perceptions towards participating in CTs.

Results

A total of 148 (63.8%) respondents were males, and 52 (22.4%) participants had been invited to participate in a CT previously. Of those, 39 (75%) participated. Knowledge about the essential elements of informed consent ranged from 55.7% (number of participants needed) to 85.7% (confidentiality of personal information). The majority (163, 73.8%) of respondents was willing to participate in a CT after consulting their family physician and 130 (58.0%) respondents would be motivated to participate in a CT if they were healthy. Only 36.8% of the respondents believed that patients who participated in a CT received the best care. Moreover, 110 (48.7%) respondents believed that research was conducted in a responsible and ethical manner.

Conclusions

The present study assessed the current understanding of CTs among Saudi participants. Although the majority of participants had an acceptable level of knowledge about CTs, they exhibited conditional attitudes and misperceptions towards participating in a CT. Increased patient awareness may improve patients’ attitudes towards ethical conduct of CTs.     

Induction of IL-10 and TGFβ from CD4+CD25+FoxP3+ T Cells Correlates with Parasite Load in Indian Kala-azar Patients Infected with Leishmania donovani

Background

Visceral leishmaniasis (VL) is distinguished by a complex interplay of immune response and parasite multiplication inside host cells. However, the direct association between different immunological correlates and parasite numbers remains largely unknown.

Methodology/Principal Findings

We examined the plasma levels of different disease promoting/protective as well as Th17 cytokines and found IL-10, TGFβ and IL-17 to be significantly correlated with parasite load in VL patients (r = 0.52, 0.53 and 0.51 for IL-10, TGFβ and IL-17, respectively). We then extended our investigation to a more antigen-specific response and found leishmanial antigen stimulated levels of both IL-10 and TGFβ to be significantly associated with parasite load (r = 0.71 and 0.72 for IL-10 and TGFβ respectively). In addition to cytokines we also looked for different cellular subtypes that could contribute to cytokine secretion and parasite persistence. Our observations manifested an association between different Treg cell markers and disease progression as absolute numbers of CD4⁺CD25⁺ (r = 0.55), CD4⁺CD25^hi (r = 0.61) as well as percentages of CD4⁺CD25⁺FoxP3⁺ T cells (r = 0.68) all correlated with parasite load. Encouraged by these results, we investigated a link between these immunological components and interestingly found both CD4⁺CD25⁺ and CD4⁺CD25⁺FoxP3⁺ Treg cells to secrete significantly (p<0.05) higher amounts of not only IL-10 but also TGFβ in comparison to corresponding CD25^- T cells.

Conclusions/Significance

Our findings shed some light on source(s) of TGFβ and suggest an association between these disease promoting cytokines and Treg cells with parasite load during active disease. Moreover, the direct evidence of CD4⁺CD25⁺FoxP3⁺ Treg cells as a source of IL-10 and TGFβ during active VL could open new avenues for immunotherapy towards cure of this potentially fatal disease.     

Copper Oxide Nanomaterials Derived from Zanthoxylum armatum DC. and Berberis lycium Royle Plant Species: Characterization,Assessment of Free Radical Scavenging and Antibacterial Activity

Copper oxide nanomaterials were synthesized by a facile sustainable biological method using two plant species (Zanthoxylum armatum DC. and Berberis lycium Royle ). The formation of materials was confirmed by FT‐IR, ATR, UV‐visible, XRD, TEM, SEM, EDX, TGA and PL. The antibacterial activity was evaluated by agar well diffusion method to ascertain the efficacy of plant species extract and extract derived copper oxide nanomaterials against six Gram‐positive bacteria namely Staphylococcus aureus, Streptococcus mutans, Streptococcus pyogenes, Corynebacterium diphtheriae, Corynebacterium xerosis, Bacillus cereus and four Gram‐negative bacteria such as Klebsiella pneumonia, Escherichia coli, Pseudomonas aeruginosa and Proteus vulgaris against the standard drug, Ciprofloxacin for Gram‐positive and Gentamicin for Gram‐negative bacteria, respectively. In both cases, copper oxide nanomaterials were found to be sensitive in all the bacterial species. Sensitivity of copper oxide nanomaterials shows an be higher as compared to plant species extract against different bacteria. Scavenging activity of plant extracts along with nanomaterials have been accessed using previously reported protocols employing ascorbic acid as standard. Scavenging activity of copper oxide nanomaterials shows an increase with increase in concentration. The biological activity (bactericidal and scavenging efficiency) of plant derived copper oxide nanomaterials revealed that these materials can be used as potent antimicrobial agent and DPPH scavengers in industrial as well as pharmacological fields.