Durvalumab and taxane family combination therapy enhances the antitumoral effects for NSCLC: An in vitro study.

Immunotherapy has lately become the most preferred cancer treatment method, and for non-small cell lung cancer (NSCLC) first-line treatment, there are many immunotherapy options. This study aimed to assess the effectiveness and toxicity of paclitaxel (PTX), docetaxel (DTX) chemotherapy, immune checkpoint inhibitor treatment (durvalumab; DVL), and their combination in NSCLC. A-549 cells were treated with DVL in combination with PTX and DTX (a quarter of the IC50 ) to investigate their anticancer effects on these cells. The MTT assay, wound healing tests, and double-staining with Annexin V/PI were used to assess the cell viability, apoptosis, and migration. The results showed that a combination of 0.35 mg/mL DVL with 6.5 µg/mL PTX and 1.75 µg/mL DTX produced a synergistic effect with CI values of 0.88, 0.37, and 0.81, respectively. Moreover, the PTX + DTX + DVL combination led to a significantly increased apoptotic rate up to 88.70 ± 3.39% in the A549 cell line compared to monotherapy (p < .001). In addition, we found that the combination therapy with these agents increased the expression level of Bax, Cas-3, p53, and Bax/Bcl-2 ratio in all experimental groups. In conclusion, the results suggest that combining anti-PD-L1 antibody therapy with chemotherapy may provide a promising approach to enhance treatment outcomes and be a potentially efficacious strategy for treating NSCLC patients. Further research and clinical investigations are needed to elucidate the underlying molecular mechanisms and validate the therapeutic potential of these compounds in vivo.

Immune Features of Tumor Microenvironment: A Genetic Spotlight.

A tumor represents a highly intricate tissue entity, characterized by an exceptionally complex microenvironment that starkly contrasts with the typical physiological surroundings of healthy tissues. Within this tumor microenvironment (TME), every component and factor assume paramount importance in the progression of malignancy and exerts a pivotal influence on a patient's clinical outcome. One of the remarkable aspects of the TME is its remarkable heterogeneity, not only across different types of cancers but even within the same histological category of tumors. In-depth research has illuminated the intricate interplay between specific immune cells and molecules and the dynamic characteristics of the TME. Recent investigations have yielded compelling evidence that several mutations harbored by tumor cells possess the capacity to instigate substantial alterations in the TME. These mutations, often acting as drivers of tumorigenesis, can orchestrate a cascade of events that remodel the TME, thereby influencing crucial aspects of cancer behavior, including its invasiveness, immune evasion, and response to therapies. It is within this nuanced context that the present study endeavors to provide a concise yet comprehensive summary of how specific mutations, within the genetic landscape of cancer cells, can instigate profound changes in TME features. By elucidating the intricate relationship between genetic mutations and the TME, this research aims to contribute to a deeper understanding of cancer biology. Ultimately, the knowledge gained from this study holds the potential to inform the development of more targeted and effective treatments, thereby offering new hope to patients grappling with the complexities of cancer.

Diagnostic Significance of Hypomethylated IGFBP3 and TWIST1 Genes in Patients with Colorectal Cancer.

Background: Colorectal cancer (CRC) has been often the main reason for dying worldwide. Many factors are implicated in the progress of colorectal carcinoma, one of the chiefs of which is DNA methylation. Insulin-like growth factor-binding protein 3 (IGFBP3) and twist homolog 1 (TWIST1) genes have already been studied and are potential biomarkers for early colorectal diagnosis. Therefore, we designed this research to assess the levels of methylation of these genes in stool specimens of patients with CRC. Materials and Methods: A whole of 80 specimens containing 40 stool specimens from CRC patients and 40 specimens from healthy individuals as a control group was investigated. DNA was extracted using the bisulfate method and methylation of the candidate genes was assessed using methylation-sensitive high-resolution melting method. Differences in the methylation levels between CRC patients and controls were assessed by statistical analysis. Results: Our study showed significant hypomethylation in both IGFBP3 and TWIST1 promoters in patients' samples compared with normal individuals and notably the promoter hypomethylation found in these genes appeared to occur simultaneously (P < 0.0001 and P < 0.0025, respectively). Meantime, hypomethylation of these genes had not any significant connection with medical results. Conclusion: Our results propose that the IGFBP3 and TWIST1 genes' methylation status can serve as potential biomarkers for early CRC diagnosis. However, more studies are still necessary to better appreciate the methylation pattern of these two genes in CRC and to prove their effects on protein levels.

Expression and promoter methylation of mitogen-activated protein kinase 1 in tumor and marginal cells of breast cancer.

AIM: In the present study, we sought to explore potential differences in the expression and promoter methylation of mitogen-activated protein kinase 1 (MAPK1) between tumor and marginal cells of breast cancer lesions. METHODS: A total of 50 randomly selected patients with breast cancer (BCa) undergoing needle biopsy were enrolled. Clinical specimens containing both tumor and marginal cells were collected and preserved. After DNA extraction using specific primers, MAPK1 mRNA and promoter methylation were measured with spectrophotometry at 260/280 nm absorption wavelengths. To deliver a comparative analysis, data from The Cancer Genome Atlas (TCGA) program regarding breast cancer (BRCA), were downloaded from Xena Functional Genomics Explorer and separately analyzed. The suitability of MAPK1 expression and promoter methylation as biomarkers for BCa was analyzed with receiver operating characteristic (ROC) curves. RESULTS: We found a positive correlation between tumor stage and MAPK1 expression (P-value: 0.029) in BCa. Likewise, MAPK1 expression was significantly associated with lymph node metastasis (P-value: 0.018). There was a significant difference in the expression of MAPK1 mRNA between tumor and marginal cells of BCa and BRCA (P-value < 0.001). However, we did not find any statistically significant difference in MAPK1 promoter methylation between tumor and marginal cells of both BCa and BRCA. With an area under the curve (AUC) of 0.71, the diagnostic accuracy of MAPK1 expression in BCa and BRCA was validated. However, MAPK1 promoter methylation was not found to be a suitable biomarker. CONCLUSION: Our findings suggest that while MAPK1 expression, might be a promising biomarker for evaluating oncogenic activity in patients suspected of BCa. We were not able to detect a prognostic/diagnostic role for MAPK1 promoter methylation.

VISTA and its ligands: the next generation of promising therapeutic targets in immunotherapy.

V-domain immunoglobulin suppressor of T cell activation (VISTA) is a novel negative checkpoint receptor (NCR) primarily involved in maintaining immune tolerance. It has a role in the pathogenesis of autoimmune disorders and cancer and has shown promising results as a therapeutic target. However, there is still some ambiguity regarding the ligands of VISTA and their interactions with each other. While V-Set and Immunoglobulin domain containing 3 (VSIG-3) and P-selectin glycoprotein ligand-1(PSGL-1) have been extensively studied as ligands for VISTA, the others have received less attention. It seems that investigating VISTA ligands, reviewing their functions and roles, as well as outcomes related to their interactions, may allow an understanding of their full functionality and effects within the cell or the microenvironment. It could also help discover alternative approaches to target the VISTA pathway without causing related side effects. In this regard, we summarize current evidence about VISTA, its related ligands, their interactions and effects, as well as their preclinical and clinical targeting agents.

The cross-talk between leptin and circadian rhythm signaling proteins in physiological processes: a systematic review.

BACKGROUND: Today, modern lifestyles and disrupted sleep patterns cause circadian clock rhythm impairments that are associated with altered leptin levels, which subsequently affect a wide range of physiological processes and have significant health burdens on societies. Nevertheless, there has been no systematic review of circadian clock genes and proteins, leptin, and related signaling pathways. METHODS: Accordingly, we systematically reviewed circadian clock proteins, leptin, and molecular mechanisms between them by searching Pubmed, Scopus, ProQuest, Web of Sciences, and Google Scholar until September 2022. After considering the inclusion and exclusion criteria, 20 animal studies were selected. The risk of bias was assessed in each study. RESULTS: The results clarified the reciprocal interconnected relationship between circadian clock genes and leptin. Circadian clock genes regulate leptin expression and signaling via different mechanisms, such as CLOCK-BMAL1 heterodimers, which increase the expression of PPARs. PPARs induce the expression of C/EBPα, a key factor in upregulating leptin expression. CLOCK-BMAL1 also induces the expression of Per1 and Rev-erb genes. PER1 activates mTORC1 and mTORC1 enhances the expression of C/EBPα. In addition, REV-ERBs activate the leptin signaling pathway. Also, leptin controls the expression of circadian clock genes by triggering the AMPK and ERK/MAPK signaling pathways, which regulate the activity of PPARs. Moreover, the roles of these molecular mechanisms are elucidated in different physiological processes and organs. CONCLUSIONS: Crosstalk between circadian clock genes and leptin and their affecting elements should be considered in the selection of new therapeutic targets for related disorders, especially obesity and metabolic impairments.

Suppression of E6 Oncogene Induces Apoptosis in CaSki Cervical Cancer Cells.

OBJECTIVE: The most important casuse of cervical cancer incidence and high mortality rate is infection to the human papillomavirus (HPV). The aim of the present study was to investigate the effect of silencing HPV E6 oncogene on cervical cancer cells using specific siRNAs. MATERIALS AND METHODS: CaSki cervical cancer cells, carrying E6 gene, were cultured and then transfected with E6 targeting siRNAs. The cell viability through suppression of E6 expression was explored using MTT assay. Besides, apoptosis induction was investigated by means of flow cytometry using Annexin / PI staining. The changes in the expression of target genes were examined via  Real-Time PCR. RESULTS: E6 gene silencing caused a significant decrease in the survival rate of CaSki cells through remarkable enhancement of apoptosis induction. Moreover, E6 suppression led to significant upregulation of P53, Bax, Caspase-3, and Caspase-9 mRNA expression while downregulated Bcl-2 expression. Interestingly, it was found that suppression of E6 expression could lead to upregulation of  E5 and E7 expression as a compensatory mechanism for E6 deactivation. CONCLUSION: According to the results of this study, suppression of E6 expression using specific siRNAs could be considered as a therapeutic approach for cervical cancer.

Association of Promoter Methylation Patterns with Expression of MAPK14 in Tissue of Papillary Thyroid Cancer Patients.

BACKGROUND: Thyroid cancer is one of the most prevalent malignancies worldwide. Genetic and epigenetic alterations are one of the main causes of thyroid tumor that is responsible to the activation of oncogenes as well as the inactivation of tumor suppressor genes. This research aimed to investigate the relationship of promoter methylation patterns with the expression of P38α in Iranian patients with thyroid cancer. METHODS: We collected 40 thyroid tumor samples and 40 adjacent normal thyroid samples from 40 Iranian patients with papillary thyroid cancer. The promoter methylation pattern of P38α gene was investigated by methylation-sensitive high-resolution melting (MS-HRM) method. Moreover, mRNA expression of P38α was investigated by Real-Time PCR method. Further validation of the obtained results was performed by the Cancer Genome Atlas (TCGA) dataset. RESULTS: The obtained results indicated that the expression of the P38α (MAPK-14) gene in the thyroid cancer sample was considerably higher than tumor margin sample. Also, P38α gene promoter methylation was higher in thyroid margin tissue as compared to tumor tissue. These results were additionally confirmed by TCGA analysis. The receiver operating characteristic (ROC) curve analysis showed a high accuracy of P38α gene expression as a diagnostic biomarker for thyroid malignancy. CONCLUSION: Our study demonstrated that the P38α expression level gene was associated with thyroid cancer pathogenesis among the Iranian population. We suggested that this gene expression might be used as a biomarker for diagnosis of thyroid tumor.

The Epigenetic Contribution to the Pathogenesis of Psoriasis: Recent Advances.

Psoriasis is defined as a chronic autoimmune disorder of the skin in which abnormal proliferation and differentiation of keratinocytes are blamed as the central culprit of disease etiopathogenesis. A complex interplay between environmental factors and genetic risk factors has been suggested to trigger the disease. However, epigenetic regulation appears to connect external stimuli and genetic abnormalities in the development of psoriasis. The discordance in the prevalence of psoriasis between monozygotic twins and environmental factors that contribute to its onset have caused a paradigm shift regarding the mechanisms underlying the pathogenesis of this disease. Epigenetic dysregulation may be involved in aberrancies of keratinocyte differentiation, T-cell activation, and other plausible cells, leading to the initiation and perpetuation of psoriasis. Epigenetics is characterized by heritable alterations in the transcription of genes without nucleotide change and is commonly considered at three levels, i.e., DNA methylation, histone modifications, and microRNAs. To date, scientific evidence has indicated abnormal DNA methylation, histone modifications, and non-coding RNA transcription in psoriatic patients. In order to reverse aberrant epigenetic changes in psoriasis patients, several compounds and drugs (epi-drugs) have been developed to affect the major enzymes involved in the methylation of DNA, or the acetylation of histones, which aim to correct the aberrant methylation and acetylation patterns. A number of clinical trials have suggested the therapeutic potential of such drugs in the treatment of psoriasis. In the present review, we attempt to clarify recent findings with respect to epigenetic irregularities in psoriasis and discuss future challenges.

Down-regulation and Clinic-pathological Correlation of SIK-1 and SIK-1-LNC in Non-small Cell Lung Cancer Patients

BACKGROUND: Non-small-cell lung cancer (NSCLC) is currently the leading cause of mortality cancer. Introducing noninvasive approaches to diagnose NSCLC, especially at an early phase, might improve the disease's prognosis. Long noncoding RNAs (lncRNAs), which are important regulators of the expression genes inside the cells, have been linked to a range of biological processes, such as cancer progression and metastasis, including NSCLC. The present work aims to determine the potential involvement of SIK-1-LNC and SIK-1 in NSCLC pathogenesis and the possible use of these molecules as novel biomarkers or therapeutic targets. METHODS: In this work, the expression levels of SIK-1-LNC and SIK-1 in 50 pairs of NSCLC tumor and tumor marginal tissues were evaluated. So, after total RNA extraction and complementary DNA synthesis, the SIK-1-LNC and SIK-1 expression levels were evaluated by real-time PCR. In the study groups, clinical and pathological characteristics of the NSCLC patients were also examined. RESULTS: Our findings showed that tumor samples had much lower levels of SIK-1 and SIK-1-LNC expression than tumor margin samples. SIK-1-LNC expression was correlated with SIK-1 levels in NSCLC samples. Interestingly, both stage and lymph node metastasis features of the tumor were associated significantly with SIK-1 and SIK-1-LNC expression levels. A ROC curve analysis indicated a biomarker index of 0.69 and 0.74 for SIK-1 and SIK-1-LNC, respectively. CONCLUSION: Collectively, our study emphasized the role of SIK-1-LNC and SIK-1 downregulation in NSCLC oncogenesis. Additionally, SIK-1 and SIK-1-LNC, particularly the latter, have shown remarkable potential to be utilized as new NSCLC biomarkers and therapeutic targets.

Association of the Toll-like receptor 4 and NOX4 gene and protein levels in asthmatic patients with metabolic syndrome: A case-control study.

Background: Understanding the contributing of influence inflammatory biomarkers in asthmatic patients with metabolic syndrome is more important. Whereby, the present study considering the important association of NADPH oxidase4 (NOX4) and Toll- like receptor4 (TLR4) in the respiratory inflammatory responses in asthmatic patients with metabolic syndrome (AS-MetS) and asthmatic (AS) patients. Materials and Methods: In this case-control study, 30 AS and 34 AS-MetS patients were enrolled. The Peripheral blood mononuclear cells (PBMCs) mRNA and protein levels of TLR4 and NOX4 were measured by qRT-PCR and western blot, respectively. Then their correlation was evaluated. Results: The significant down-regulation of mRNA and protein PBMCs expression levels of TLR4 were observed in the AS-MetS group in comparison to AS one (P=0.03), but the NOX4 expression was non-significant. Additionally, the significant correlation was exhibited between mRNA expression levels of NOX4 and TLR4 in both AS-MetS (r= 0.440, P=0.009) and AS groups (r=0.909, P=0.0001). The association between TLR4 mRNA level and triglyceride in AS-MetS group (r=0.454, P=0.008,) and also white blood cells (WBC) in AS group (r= -0.507, P=0.006,) were significant. Conclusion: The metabolic syndrome can significantly influence the expressions of TLR4 in AS-MetS. This study indicated that TLR4 and NOX4 altogether may provide valuable molecular knowledge of their relation with metabolic syndrome criteria for finding major pathways in different phenotype of asthma.

Oxidative stress indices induced by industrial and urban PM2.5-bound metals in A549 cells.

The detrimental effects of atmospheric fine particulate matter (PM2.5) on human health are of major global concern. PM2.5-bound metals are toxic compounds that contribute to cellular damage. To investigate the toxic effects of water-soluble metals on human lung epithelial cells and their bioaccessibility to lung fluid, PM2.5 samples were collected from both urban and industrial areas in the metropolitan city of Tabriz, Iran. Oxidative stress indices, including proline content, total antioxidant capacity (TAC), cytotoxicity, and DNA damage levels of water-soluble components of PM2.5, were evaluated. Furthermore, an in vitro test was conducted to assess the bioaccessibility of various PM2.5-bound metals to the respiratory system using simulated lung fluid. PM2.5 average concentrations in urban and industrial areas were 83.11 and 97.71 µg/m3, respectively. The cytotoxicity effects of PM2.5 water-soluble constituents from urban areas were significantly higher than in industrial areas and the IC50 was found to be 96.76 ± 3.34 and 201.31 ± 5.96 µg/mL for urban and industrial PM2.5 samples, respectively. In addition, higher PM2.5 concentrations increased the proline content in a concentration-dependent manner in A549 cells, which plays a protective role against oxidative stress and prevents PM2.5-induced DNA damage. Also, the partial least squares regression revealed that Be, Cd, Co, Ni, and Cr, were significantly correlated with DNA damage and proline accumulation, which caused cell damage through oxidative stress. The results of this study showed that PM2.5-bound metals in highly polluted metropolitan city caused substantial changes in the cellular proline content, DNA damage levels and cytotoxicity in human lung A549 cells.

MicroRNA-Based Biomarkers in Lung Cancer: Recent Advances and Potential Applications.

INTRODUCTION: MicroRNAs (miRNAs) are a group of small noncoding RNAs (ncRNAs) that post-transcriptionally control the expression of genes by binding and degrading their target mRNAs. miRNAs can function as possible tumor suppressors or oncogenes in various cancers. Lately, miRNAs application as a biomarker (prognosis and diagnosis) for different diseases has gained much attention. miRNAs exist in a stable form in several biological materials, including tissue, plasma, and serum. The noninvasive and easy screening of miRNAs in serum, blood, tissue, and other body fluids and acceptable stability make microRNA a noticeable factor as biomarkers in human malignancies. MATERIALS AND METHODS: In this review, we searched some online databases like Web of Science, Embase, and PubMed to find eligible manuscripts up to the end of 2021. RESULTS: Abnormal expressions of these molecules are associated with the incidence of many illnesses like cancer. Therefore, they are candidates as a molecular tool for noninvasive tumor prognosis and diagnosis. In the current study, we introduce important miRNAs that may be used as prognostic and diagnostic markers in lung cancer patients. CONCLUSION: We summarized the latest reports about critical miRNAs related to the diagnosis and prognosis in lung patients.

Novel diagnostic potential of miR-1 in patients with acute heart failure.

BACKGROUND: A number of circulating micro-ribonucleic acids (miRNAs) have been introduced as convincing predictive determinants in a variety of cardiovascular diseases. This study aimed to evaluate some miRNAs' diagnostic and prognostic value in patients with acute heart failure (AHF). METHOD: Forty-four AHF patients were randomly selected from a tertiary heart center, and 44 healthy participants were included in the control group. Plasma levels of assessed miRNAs, including miR -1, -21, -23, and -423-5-p were measured in both groups. The patients were followed for one year, and several clinical outcomes, including in-hospital mortality, one-year mortality, and the number of readmissions, were recorded. RESULTS: An overall 88 plasma samples were evaluated. There was no significant difference in terms of demographic characteristics between the AHF and healthy groups. Our findings revealed that mean levels of miR-1, -21, -23, and -423-5-p in AHF patients were significantly higher than in the control group. Although all assessed miRNAs demonstrated high diagnostic potential, the highest sensitivity (77.2%) and specificity (97.7%) is related to miR-1 for the values above 1.22 (p = 0.001, AUC = 0.841; 95%CI, 0.751 to 946). Besides, the levels of miR-21 and -23 were significantly lower in patients with ischemia-induced HF. However, the follow-up data demonstrated no significant association between miRNAs and prognostic outcomes including in-hospital mortality, one-year mortality, and the number of readmissions. CONCLUSION: The result of our study demonstrated that miR-1, -21, -23, and -423-5-p can be taken into account as diagnostic aids for AHF. Nevertheless, there was no evidence supporting the efficacy of these miRNAs as prognostic factors in our study.

Regulatory Effect of let-7f Transfection in Non-Small Cell Lung Cancer on its Candidate Target Genes.

Background: Let-7f has essential impacts on biological processes; however, its biological and molecular functions in lung cancer pathogenesis have yet been remained unclear. We aimed to investigate the expression level of let-7f and its candidate target genes both in lung cancer tissues and A549 cell line. Methods: Bioinformatics databases were first used to select candidate target genes of let-7f. Then the relative gene and protein expressions of let-7f and its target genes, including HMGA2, ARID3B, SMARCAD1, and FZD3, were measured in lung tissues of NSCLC patients and A549 cell line using qRT-PCR and Western blotting. The electroporation method was used to transfect A549 cells with let-7f mimic and microRNA inhibitor. The impact of let-7f transfection on the viability of A549 cells was assessed using MTT assay. The expression data of studied genes were analyzed statistically. Results: Results indicated significant downregulated expression level of let-7f-5p (p = 0.0013) and upregulated level of the HMGA2 and FZD3 in NSCLC cases (p < 0.05). In A549 cells, after transfection with let-7f mimic, the expression of both mRNA and protein levels of HMGA2, ARID3B, SMARCAD1, and FZD3 decreased. Also, the overexpression of let-7f significantly inhibited the A549 cell proliferation and viability (p = 0.017). Conclusion: Our findings exhibited the high value of let-7f and HMGA2 as biomarkers for NSCLC. The let-7f, as a major tumor suppressor regulatory factor via direct targeting genes (e.g. HMGA2), inhibits lung cancer cell viability and proliferation and could serve as a marker for the early diagnostic of NSCLC.

Combination Therapy with KRAS and P38α siRNA Suppresses Colorectal Cancer Growth and Development in SW480 Cell Line.

PURPOSE: Colorectal cancer (CRC) is one of the most prevalence malignancies in a different society with a high rate of death. The KRAS and p38α axes have critical roles in the development, migration, and growth of numerous tumors, such as colorectal malignancy. KRAS mutation acts as an oncogene in various cancers and is correlated with the poor prognosis in colorectal tumors. Also, p38α plays different roles and exhibits tissue-dependent activity. In some tissues act as an oncogene while in others act as a tumor suppressor. In this research, we try to understand the effect of the P38α and KRAS genes suppression by specific siRNAs on the SW480 cell line progression. METHODS: We evaluate the impact of the P38α and KRAS gene knockdown by special siRNA on the growth and development of the SW480 cell line. SW480 cell line was treated with KRAS and P38α siRNAs, and the cell viability, gene expression, migration ability, and rate of apoptosis were evaluated with MTT assay, real-time PCR, scratch test, and flow cytometry. RESULTS: After treatment of the cancer cell with KRAs and P38α siRNAs, cell viability reduced to 29.16%. Also, the expression levels of the KRAS and P38α genes reduced to 26.34% and 16.06%, respectively. Apoptosis rate after combination therapy with KRAS and P38α siRNAs increased to 72.1. Also, we found that these siRNAs suppress cell migration in SW480 cell lines. CONCLUSION: The current study showed that combination therapy with p38α and KRAS siRNA may be considered a novel therapy for colorectal tumor in future.

The oxidative and neurotoxic potentials of the ambient PM2.5 extracts: The efficient multi-solvent extraction method.

The health effects of ambient air particulate matter with a diameter of ≤2.5 µm (PM2.5) on the central nervous system are well known and the induced oxidative stress has been shown as their main neuropathologic outcome. Ambient air PM2.5 sampling methods mostly use air sampler systems that collect PM2.5 on filters, which is followed by a PM2.5 extraction approach. Inefficient extraction may lead to compositional bias and unreal interpretation of the results. This study aimed to compare our proposed multi-solvent extraction (MSE) approach for PM2.5 extraction with a conventional aqueous extraction (AqE) method using the analysis of oxidative effects and cytotoxicity in the human neuroblastoma SH-SY5Y cell line. Ambient PM2.5 samples were collected from an urban traffic location in Tehran city, the capital of Iran, using a high-volume sampler. The developed MSE method was proved to have superior advantages over the AqE method including an increased extraction efficiency (as much as 96 against 48% for PMms and PMaq, respectively), and decreased artifacts and compositional biases. Ambient PM2.5, besides PMms and PMaq were analyzed for water-soluble ions, metals, and major elements. Dithiothreitol, ascorbic acid, lipid peroxidation, and cell viability assays on SH-SY5Y cells represented the significantly higher oxidative potential for PMms compared to PMaq. The increased cytotoxicity may occur because of the increased oxidative potential of PMms and possibly is associated with higher efficiency of the MSE over the AqE method for removal of total redox-active PM components.

Significance of microRNA-330-5p/TYMS Expression Axis in the Pathogenesis of Colorectal Tumorigenesis.

BACKGROUND: Colorectal cancer (CRC) is one of the most common types of cancer worldwide. A number of dysregulated microRNAs (miRNAs) have been linked to CRC progression and treatment response and are thought to be promising prognostic biomarkers for this cancer. microRNA-330 (miR-330-5p) has been reported to inhibit cell proliferation through suppressing thymidylate synthase (TYMS). In the current study, miR-330-5p, TYMS, and their interactions were investigated to evaluate their therapeutic and diagnostic value for CRC treatment. METHODS: The expression levels of miR-330-5p and TYMS were evaluated in silico using TCGA datasets for CRC. Data validation was performed on a set of internal samples (100 pairs of CRC tumor specimens and adjacent non-cancerous samples) utilizing real-time PCR assay. The linkage between clinicopathological parameters and expression levels was also investigated. RESULTS: TCGA results indicated that miR-330-5p and TYMS were significantly upregulated and downregulated in the CRC, respectively. Real-time PCR results confirmed that the expression of miR-330-5p was significantly upregulated in tumor tissues relative to marginal tissues (P = 0.0005), whereas TYMS expression was significantly downregulated (P = 0.0001). The transcript level of miR-330-5p was associated with tumor stage and lymph node metastases. CONCLUSION: The microRNA-330 inhibited cell proliferation by suppressing thymidylate synthase (TYMS) in colorectal cancer. Therefore, suggesting that they are valuable factors for further studies of alternative treatment and diagnostic methods.

Prospects for Manipulation of Mesenchymal Stem Cells in Tumor Therapy: Anti-Angiogenesis Property on the Spotlight.

The interactions between the tumor microenvironment and the tumor cells confers a condition that accelerate or decelerate the development of tumor. Of these cells, mesenchymal stem cells (MSCs) have the potential to modulate the tumor cells. MSCs have been established with double functions, whereby contribute to a tumorigenic or anti-tumor setting. Clinical studies have indicated the potential of MSCs to be used as tool in treating the human cancer cells. One of the advantageous features of MSCs that make them as a well-suited tool for cancer therapy is the natural tumor-trophic migration potential. A key specification of the tumor development has been stablished to be angiogenesis. As a result, manipulation of angiogenesis has become an attractive approach for cancer therapy. This review article will seek to clarify the anti-angiogenesis strategy in modulating the MSCs to treat the tumor cells.