The frequency of NRAS mutation in stool samples of Iranian colorectal cancers compared to Finnish patients.

Background: Stools from colorectal cancer patients are noninvasive samples that could be used to compare the frequency of hotspot mutations between two different ethnic cohorts. Materials and Methods: We collected stool samples from the Iranian cohort (52 patients and 49 controls) and the Finnish cohort (40 patients and 14 controls). Following stool DNA extraction, we used the AmpliSeq Colon and Lung Cancer panel to prepare DNA libraries before sequencing. Results: The Iranian cohort exhibited 35 hotspot mutations in the BRAF, ERBB4, FBXW7, FGFR1, FGFR3, KRAS, MAP2K, MET, NRAS, PIK3C, SMAD4, and TP53 genes. In the Finnish cohort, 13 hotspot mutations were found in the AKT1, APC, KIT, KRAS, SMO, STK11, and TP53 genes. Mutations in NRAS and FGFR3 were observed only in the Iranian cohort, while APC mutations were exclusive for the Finnish cohort. Conclusion: Genes involved in MAPK and PI3K-MAPK pathways showed a higher frequency of mutations in Iranian patients which may have therapeutic implications.

Clinical Implications and Prognostic Value of Leucine-Rich G Protein-Coupled Receptor 5 Expression as A Cancer Stem Cell Marker in Malignancies: A Systematic Review and Meta-Analysis.

Leucine-rich G protein-coupled receptor 5 (LGR5) is a marker of cancer stem cells (CSCs) in various cancers. Based on different studies, conflicting reports exist on correlation between LGR5 expression and poor prognosis/ clinicopathological parameters in cancer patients. Therefore, our purpose in conducting this study was to investigate correlation between LGR5 expression and outcomes of cancer patients under study through a systematic review and meta-analysis. Relevant articles were searched and collected using EMBASE, PubMed, Science Direct, and Scopus databases until December 21, 2022. This study was conducted to examine correlation between LGR5 expression and different clinical outcomes, such as recurrence-free survival (RFS), disease-free survival (DFS), overall survival (OS), and clinicopathological characteristics of the included cancer patients. To achieve this, hazard ratios (HRs) with 95% confidence intervals (CIs) and odds ratios (ORs) with 95% CIs were used as statistical measures. A meta-analysis was conducted using STATA 12.0 software. Finally, 53 studies including 9523 patients met the inclusion criteria. Significantly, high-level expression of LGR5 was related to poor prognosis in terms of OS, higher tumor stage, presence of distant metastasis, and presence of lymph node metastasis. It was discovered through subgroup analysis that several factors, including the study area, evaluation method, and type of cancer, can influence the correlation between LGR5 expression and negative prognosis in cancer patients. According to the results of our study, LGR5 overexpression was related to poor OS in cancer patients. In addition, clinicopathological data indicated an unfavorable prognosis in cancer patients with high LGR5 expression. In conclusion, LGR5 may serve as a potential prognostic marker for predicting survival in certain cancer types.

Retraction notice to "The therapeutic potential of human adipose-derived mesenchymal stem cells producing CXCL10 in a mouse melanoma lung metastasis model" [Cancer Lett. 419 (2018) 30-39].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor. After publication, the Editors were contacted by a concerned reader regarding alleged image duplication. These allegations are in regard to Fig. 3a being duplicated from a previously published paper in the journal Stem Cells (Stem Cells. 2008 Sep;26 (9):2332-8. doi: 10.1634/stemcells.2008-0084) and Fig. 8a being duplicated from a previously published paper in the journal Molecular Cancer (Mol Cancer 13, 255 (2014). https://doi.org/10.1186/1476-4598-13-255). After a thorough investigation by the editorial team, the Editors determined that there are multiple identical details between Fig. 5A (Cancer Letters) and Fig. 3A (Stem Cells) and the authors did not produce satisfactory evidence that the published images in Cancer Letters were original. Due to this, the Editor does not have confidence in the results and conclusions presented and has made the decision to retract.

Therapeutic approaches for Type 1 Diabetes: Promising cell-based approaches to achieve ultimate success.

Type 1 Diabetes mellitus (T1DM) is a chronic metabolic disorder characterized by pancreatic ß-cells destruction. Despite substantial advances in T1DM treatment, lifelong exogenous insulin administration is the mainstay of treatments, and constant control of glucose levels is still a challenge. Endogenous insulin production by replacing insulin-producing cells is an alternative, but the lack of suitable donors is accounted as one of the main obstacles to its widespread application. The research and trials overview demonstrates that endogenous production of insulin has started to go beyond the deceased-derived to stem cells-derived insulin-producing cells. Several protocols have been developed over the past couple of years for generating insulin-producing cells (IPCs) from various stem cell types and reprogramming fully differentiated cells. A straightforward and quick method for achieving this goal is to investigate and apply the ß-cell specific transcription factors as a direct strategy for IPCs generation. In this review, we emphasize the significance of transcription factors in IPCs development from different non-beta cell sources, and pertinent research underlies the marked progress in the methods for generating insulin-producing cells and application for Type 1 Diabetes treatment.

Immunotherapies targeting tumor vasculature: challenges and opportunities.

Angiogenesis is a hallmark of cancer biology, and neoadjuvant therapies targeting either tumor vasculature or VEGF signaling have been developed to treat solid malignant tumors. However, these therapies induce complete vascular depletion leading to hypoxic niche, drug resistance, and tumor recurrence rate or leading to impaired delivery of chemo drugs and immune cell infiltration at the tumor site. Achieving a balance between oxygenation and tumor growth inhibition requires determining vascular normalization after treatment with a low dose of antiangiogenic agents. However, monotherapy within the approved antiangiogenic agents' benefits only some tumors and their efficacy improvement could be achieved using immunotherapy and emerging nanocarriers as a clinical tool to optimize subsequent therapeutic regimens and reduce the need for a high dosage of chemo agents. More importantly, combined immunotherapies and nano-based delivery systems can prolong the normalization window while providing the advantages to address the current treatment challenges within antiangiogenic agents. This review summarizes the approved therapies targeting tumor angiogenesis, highlights the challenges and limitations of current therapies, and discusses how vascular normalization, immunotherapies, and nanomedicine could introduce the theranostic potentials to improve tumor management in future clinical settings.

Status of integrin subunit alpha 4 promoter DNA methylation in colorectal cancer and other malignant tumors: a systematic review and meta-analysis.

Background and purpose: Although many recent studies have analyzed the validation of integrin subunit alpha 4 (ITGA4) biomarker for cancer detection in patients with various malignancies, the diagnostic value of ITGA4 methylation for malignant tumors remains uncertain. We performed a systematic review and meta-analysis to unravel the relationship between ITGA4 promoter methylation status and malignant tumors. Experimental approach: A meta-analysis was performed using the metaphor package in R 3.5 and Meta-Disc 1.4 software. Data were derived from a search of main electronic databases up to January 2022. SROC analysis was used to evaluate the status of ITGA4 promoter methylation in colorectal cancer (CRC) and other cancers. A total of 1232 tumor samples and 649 non-tumor samples from 13 studies were analyzed. Findings/Results: The pooled results including all types of cancer provided evidence that ITGA4 hypermethylation was more frequent in tumor samples than non-tumor samples (OR 13.32, 95% CI 7.96-22.29). Methylation of ITGA4 has a pooled sensitivity of 0.95 (95% CI: 0.94-0.97), a pooled specificity of 0.57 (95% CI: 0.54-0.60), and an area under the curve (AUC) of 0.94. When the analysis was performed independently for CRC, it revealed a higher association (OR = 20.77, 95% CI: 9.15-47.15). The assessment of ITGA4 methylation of tissue samples resulted in a pooled sensitivity of 0.99 (95% CI: 0.97-1.00) and a pooled specificity of 0.90 (95% CI: 0.86-0.93), and AUC of 0.94 for the diagnosis of CRC. Conclusion and implications: ITGA4 methylation analysis is a reliable method for CRC screening in tissue samples.

Comparison of OX40 expression in patients with multiple sclerosis and neuromyelitis optica as an approach to diagnosis.

BACKGROUND: Previous studies have shown that CD134 (OX40) co-stimulation is involved in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) models and the antigen is expressed within multiple sclerosis lesions in humans. OX40 (CD134) is thought to be a secondary co-stimulatory immune checkpoint molecule that is expressed by T cells. This study aimed to evaluate the mRNA expression of OX40 and its serum levels in the peripheral blood of patients with Multiple Sclerosis (MS) or Neuromyelitis Optica (NMO). METHODS: Patients with MS (n = 60), NMO (n = 20), and 20 healthy subjects were recruited from Sina Hospital, Tehran, Iran. The diagnoses were confirmed by a specialist in clinical neurology. Peripheral venous blood was obtained from all subjects, and mRNA quantification of OX40 was conducted using real-time PCR. Serum samples were also obtained and the concentration of OX40 was determined using an enzyme-linked immunosorbent assay (ELISA). RESULTS: There was a significant correlation between the mRNA expression and serum levels of OX40 and disability as assessed using the expanded disability status scale (EDSS) in the patients with MS, but not in the patients with NMO. Expression of OX40 mRNA was significantly higher in the peripheral blood of MS patients compared to healthy individuals and NMO patients (*P < 0.05). In addition, serum OX40 concentrations were also significantly higher in patients with MS patients compared with healthy subjects (9.08 ± 2.48 vs. 1.49 ± 0.54 ng/ml; P = 0.041). CONCLUSIONS: It appears that an increased expression of OX40 may be associated with the hyperactivation of T cells in patients with MS, and this may play a role in the pathogenesis of the disease.

Engaging stemness improves cancer immunotherapy.

Intra-tumoral immune cells promote the stemness of cancer stem cells (CSCs) in the tumor microenvironment (TME). CSCs promote tumor progression, relapse, and resistance to immunotherapy. Cancer stemness induces the expression of neoantigens and neo-properties in CSCs, creating an opportunity for targeted immunotherapies. Isolation of stem-like T cells or retaining stemness in T clonotypes strategies produces exhaustion-resistance T cells with superior re-expansion capacity and long-lasting responses after adoptive cell therapies. Stem cells-derived NK cells may be the next generation of NK cell products for immunotherapy. Here, we have reviewed mechanisms by which stemness factors modulated the immunoediting of the TME and summarized the potentials of CSCs in the development of immunotherapy regimens, including CAR-T cells, CAR-NK cells, cancer vaccines, and monoclonal antibodies. We have discussed the natural or genetically engineered stem-like T cells and stem cell-derived NK cells with increased cytotoxicity to tumor cells. Finally, we have provided a perspective on approaches that may improve the therapeutic efficacy of these novel adoptive cell-based products in targeting immunosuppressive TME.

Single Nucleotide Polymorphism rs6445975 in the PXK Gene Is Correlated with Susceptibility and Clinical Characteristics of Systemic Lupus Erythematosus.

Background: Recently, genome-wide association studies (GWAS) have discovered several single nucleotide polymorphisms (SNPs) and loci associated with the risk of systemic lupus erythematosus (SLE). rs6445975 (T>G; intronic variant) polymorphism in the PXK gene is one of these loci. However, there was an inconsistency between the results of replicative studies on European and Asia ancestry. This study aimed to assess the possible association between rs6445975 polymorphism with SLE risk in the Iranian population. Methods: Genotype and allele distribution of rs6445975 polymorphism were investigated in 110 patients with SLE and 115 healthy controls in Isfahan University of Medical Sciences, Isfahan, Iran in 2019 via real-time PCR high resolution melting method (HRM). Results: GG and TG genotypes, but not TT genotype, were associated with increased risk of SLE (GG vs TT; OR= 7.538; 95%CI [3.47, 17.066] and TG vs TT; OR=2.21; 95%CI [1.06, 4.72]). Inheritance analysis revealed that TG + GG was correlated with the increased risk of SLE disease in the dominant model (OR=3.928; 95%CI [2.056, 7.74]). Moreover, subjects with the G allele were more frequently affected with SLE than individuals with the T allele (OR= 3.55; 95%CI [2.37, 5.36]). The G allele in patients was correlated with serum concentration of CRP, ESR, anti-dsDNA antibody, C3, and C4 and presentation of some clinical manifestations such as kidney involvements and skin lesions (P<0.05). Conclusion: Our findings suggest a substantial association between rs6445975 polymorphism in the PXK gene with susceptibility and clinical characteristics of SLE in the Iranian population.

Impact of Single Nucleotide Polymorphism in the ANKRD55 Gene on Occurrence and Clinical Characteristics of Rheumatoid Arthritis.

Background: Rheumatoid Arthritis (RA) has multifactorial etiology and numerous genetic and environmental factors have been related to an increased risk of RA. Recently, Genome-Wide Association Studies (GWAS) suggested a large number of Single Nucleotide Polymorphisms (SNPs) loci affecting the susceptibility to RA. One of these loci is rs6859219 (C>A), a functional polymorphism in the ANKRD55 gene which was associated with the expression of ANKRD55 and IL6ST. In the current study, we evaluated the possible association between rs6859219 (intronic variant) in the ANKRD55 gene with RA risk in the Iranian population. Methods: A case-control study using 118 RA patients and 115 healthy counterparts was undertaken in order to determine rs6859219 genotypes using real-time polymerase chain reaction High-Resolution Melting (HRM) method. Results: There was a significant difference in the genotype and allele frequencies of rs6859219 between patients and controls (p<0.001). Logistic regression analysis demonstrates that CC genotype and C allele increased the risk of RA (OR for CC genotype= 7.12; 95%CI [3.51-15.05]/OR for C allele=4.16; 95%CI [2.78-6.28]). Furthermore, regarding the dominant and recessive model of inheritance, RA patients indicated obvious association of the rs6859219 variant compared to healthy controls (p<0.001). Moreover, in the patient group, there was a significant correlation between C-Reactive Protein (CRP) concentration with rs6859219 polymorphism (p<0.001). Conclusion: Our findings propose a substantial correlation between rs6859219 polymorphism and RA risk and clinical characteristics of this disease in the Iranian population.

Unfavorable prognosis and clinical consequences of APOBEC3B expression in breast and other cancers: A systematic review and meta-analysis.

INTRODUCTION: Controversy exists regarding the association of apolipoprotein B mRNA editing enzyme catalytic subunit 3B APOBEC3B, (A3B) overexpression and poor prognosis, metastasis, and chemotherapy drug resistance in cancers. Here we conducted a systematic review and meta-analysis to determine its prognostic value and clinicopathological features in breast cancer and some other malignancies. MATERIALS AND METHODS: PubMed, Scopus, Cochrane Library, Web of Science, and EMBASE were searched up to Feb 2022 for the association of A3B with breast, ovarian, gastrointestinal and lung cancers. The pooled hazard ratios with 95% confidence interval (CI) were evaluated to assess disease-free survival (DFS), overall survival (OS), and recurrence-free survival (RFS) in cancers under study. RESULTS: Over 3700 patients were included in this meta-survey. Elevated levels of A3B were significantly related to low OS (pooled HR = 1.30; 95% CI:1.09-1.55, P < 0.01), poor DFS (pooled HR = 1.66; 95% CI:1.17-2.35, P < 0.01) and poor RFS (HR = 1.51, 95% CI:1.11-2.04, P = 0.01). Subgroup analysis revealed that high A3B expression was associated with poor OS in lung (HR = 1.85, 95% CI: 1.40-2.45), and breast cancers (HR = 1.38, 95% CI: 1.00-1.89). High expression of A3B did not display any significant association with clinicopathologic features. CONCLUSION: APOBEC3B overexpression is related to poor OS, DFS and RFS only in some cancer types and no generalized role could be predicted for all cancers.

Strong Association of Polymorphism in SPRED2 Gene with Disease Susceptibility and Clinical Characteristics of Rheumatoid Arthritis in the Iranian Population.

Background: The high heritability of Rheumatoid Arthritis (RA) has been estimated from different studies. Recently, Genome-Wide Association Studies (GWAS) show a large number of Single Nucleotide Polymorphisms (SNPs) loci affecting susceptibility to RA. The rs934734 polymorphism in the SPRED2 gene is one of these loci. Studies have shown that the SPRED2 gene is involved in the regulation of inflammatory response, leukocyte infiltration, and local chemokine production. In the current study, the possible association between SNP rs934734 (intronic variant) in the SPRED2 gene with RA risk in the Iranian population was evaluated. Methods: One hundred fourteen RA patients and 120 healthy counterparts were recruited in this case-control study to evaluate rs934734 genotypes using the real-time PCR High Resolution Melting method (HRM). Results: Logistic regression analysis demonstrated that GG and AG genotypes compared with AA genotype increase the risk of RA (GG vs. AA; OR=4.61; 95%CI [2.21-9.35]; p<0.001 and AG vs. AA; OR=2.54; 95%CI [1.36-4.76]; p=0.004). Furthermore, subjects with allele G were more frequently affected with RA than subjects with A allele (OR=2.33; 95%CI [1.61-3.38]; p<0.001). Besides, in the patient group, there was a significant correlation between Erythrocyte Sedimentation Rate (ESR) and C-reactive protein (CRP) concentration with rs934734 polymorphism (p<0.05). Conclusion: Our findings suggest that rs934734 in SPRED2 strongly underlies RA development and is associated with clinicopathological characteristics of this disease.

Screening of potential inhibitors of COVID-19 with repurposing approach via molecular docking.

SARS-CoV-2 (COVID-19) is the causative organism for a pandemic disease with a high rate of infectivity and mortality. In this study, we aimed to assess the affinity between several available small molecule and proteins, including Abl kinase inhibitors, Janus kinase inhibitor, dipeptidyl peptidase 4 inhibitors, RNA-dependent RNA polymerase inhibitors, and Papain-like protease inhibitors, using binding simulation, to test whether they may be effective in inhibiting COVID-19 infection through several mechanisms. The efficiency of inhibitors was evaluated based on docking scores using AutoDock Vina software. Strong ligand-protein interactions were predicted among some of these drugs, that included: Imatinib, Remdesivir, and Telaprevir, and this may render these compounds promising candidates. Some candidate drugs might be efficient in disease control as potential inhibitors or lead compounds against the SARS-CoV-2. It is also worth highlighting the powerful immunomodulatory role of other drugs, such as Abivertinib that inhibits pro-inflammatory cytokine production associated with cytokine release syndrome (CRS) and the progression of COVID-19 infection. The potential role of other Abl kinase inhibitors, including Imatinib in reducing SARS-CoV and MERS-CoV viral titers, immune regulatory function and the development of acute respiratory distress syndrome (ARDS), indicate that this drug may be useful for COVID-19, as the SARS-CoV-2 genome is similar to SARS-CoV.

Differentially methylation of IFI44L gene promoter in Iranian patients with systemic lupus erythematosus and rheumatoid arthritis.

BACKGROUND: Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are multisystemic autoimmune diseases with multifactorial nature. Considering the limitations of the current conventional serological tests for the diagnosis of these diseases, researchers strive to find more new valid biomarkers. METHODS: Sixty-nine patients with SLE, 63 patients with RA, and 71 healthy controls were recruited to evaluate the methylation level of interferon-induced protein 44-like (IFI44L) promoter. Quantitative methylation of the promoter region of the IFI44L gene was measured in extracted DNA of peripheral blood mononuclear cells (PBMCs) with methylation-quantification endonuclease-resistant DNA (MethyQESD) method. RESULTS: Our findings unveiled a drastic hypomethylation of IFI44L promoter in SLE and RA patients compared with healthy volunteers (mean: 40.23% ± 64.54%, 35.19% ± 24.09%, and 71.98% ± 23.83%, respectively; P < 0.001 for both SLE and RA). In comparison between SLE and RA patients with the control group, IFI44L promoter methylation had a sensitivity of 81.15% and 84.12%, respectively, and specificity was 76.05%. The promoter methylation level was not meaningfully different between SLE and RA patients (P = 0.267). Moreover, our analysis revealed that the methylation level of the IFI44L promoter was not significantly different between SLE disease activity and renal involvements (P > 0.05). While RA patients with a higher concentration of CRP had a lower DNA methylation level (P = 0.023). CONCLUSION: The methylation level of IFI44L promoter was lower in PBMCs of Iranian patients with SLE and RA than that in the control group. Furthermore, DNA methylation level of the IFI44L promoter had a negative correlation with RA disease activity. However, there was not a significant association with the clinical characteristics of SLE.

Association of a Functional Single Nucleotide Polymorphism (rs874040) in the RBPJ Gene with Susceptibility to Rheumatoid Arthritis in Iranian Population.

BACKGROUND: Rheumatoid Arthritis (RA) is a progressive, heterogeneous, and common multifactorial autoimmune disease. Several Genome-Wide Association Studies (GWASs) have revealed more than 100 risk loci for RA. One of these loci is a functional single nucleotide polymorphism (rs874040; G>C) near the recombination signal-binding protein for the immunoglobulin kappa J region (RBPJ) gene. RBPJ can convert into a transcriptional activator upon activation of the canonical Notch pathway. Notch signaling has recently emerged as an important regulator of immune responses in inflammation and autoimmune diseases. In the present study, the possible association between SNP rs874040 (G>C) upstream of the RBPJ gene with RA risk was assessed in Iranian population. METHODS: A case-control study including 60 RA patients and 44 control subjects was conducted to estimate rs874040 genotypes using real-time polymerase chain reaction High Resolution Melting (HRM) method. RESULTS: Logistic regression analysis indicated that homozygous CC and heterozygous GC genotypes increase the risk of RA compared with GG genotype (CC vs. GG; OR=11.36; 95% CI [3.93-33.33] and CG vs. GG; OR=3.78; 95% CI [1.30-10. 98]). Besides, subjects with C allele were more frequently affected with RA than subjects with G allele (OR=10.42; 95% CI [5.21-20.83]). Furthermore, in the patient group, a significant correlation was found between C-reactive protein concentrations and rs874040 polymorphism (p<0.05). CONCLUSION: Our findings propose a substantial correlation between rs874040 polymorphism and RA risk in Iranian population.

Single nucleotide polymorphism rs5029937 in TNFAIP3 gene is correlated with risk of rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is a progressive and common autoimmune disease with multifactorial etiology. Several pieces of research show that genetic factors play a major role in the incidence of RA. Several genome-wide association studies (GWAS) have identified the tumor necrosis factor alpha inducible protein 3 (TNFAIP3) genes as one of the candidate loci. The TNFAIP3 gene encoding ubiquitin-editing protein A20 witch restricts B cell survival and prevents autoimmunity. Previous studies have indicated that single nucleotide polymorphisms (SNPs) in the TNFAIP3 gene are correlated with several autoimmune disorders. In the present study, we assessed the possible association between SNP rs5029937 (intronic variant) in the TNFAIP3 gene with RA risk in the Iranian population. Methods: A case-control study using 50 RA patients and 50 control subjects was undertaken to evaluate rs5029937 (G>T) genotypes using real-time PCR high resolution melting method (HRM). The SPSS22 was used for statistical analyses and the significance level was set at P<0.05. Results: Logistic regression analysis demonstrates that homozygous TT + heterozygous TG genotypes compared with GG genotype increase the risk of RA (TT+TG vs GG; P= 0.004, OR= 3.46; 95%CI [1.492-8.075]). Also, individuals with allele T were more frequently affected with RA than subjects with G allele (T vs G; P= 0.004, OR= 2.61; 95%CI [1.382-4.919]). Conclusion: Our findings propose a substantial correlation between rs5029937 (G>T) polymorphism and RA risk in Iranian population.

The dysbiosis signature of Fusobacterium nucleatum in colorectal cancer-cause or consequences? A systematic review.

Colorectal cancer (CRC) is the third most common cause of cancer globally and the fourth attributable cause of mortality and morbidity due to cancer. An emerging factor contributing to CRC is the gut microbiota and the cellular changes associated with it. Further insights on this may help in the prevention, diagnosis and new therapeutic approaches to colorectal cancer. In most cases of CRC, genetic factors appear to contribute less to its aetiology than environmental and epigenetic factors; therefore, it may be important to investigate these environmental factors, their effects, and the mechanisms that may contribute to this cancer. The gut microbiota has recently been highlighted as a potential risk factor that may affect the structural components of the tumor microenvironment, as well as free radical and enzymatic metabolites directly, or indirectly. Many studies have reported changes in the gut microbiota of patients with colorectal cancer. What is controversial is whether the cancer is the cause or consequence of the change in the microbiota. There is strong evidence supporting both possibilities. The presence of Fusobacterium nucleatum in human colorectal specimens has been demonstrated by RNA-sequencing. F. nucleatum has been shown to express high levels of virulence factors such as FadA, Fap2 and MORN2 proteins. Our review of the published data suggest that F. nucleatum may be a prognostic biomarker of CRC risk, and hence raises the potential of antibiotic treatment of F. nucleatum for the prevention of CRC.

The role of hypoxia in the tumor microenvironment and development of cancer stem cell: a novel approach to developing treatment.

Hypoxia is a common feature of solid tumors, and develops because of the rapid growth of the tumor that outstrips the oxygen supply, and impaired blood flow due to the formation of abnormal blood vessels supplying the tumor. It has been reported that tumor hypoxia can: activate angiogenesis, thereby enhancing invasiveness and risk of metastasis; increase survival of tumor, as well as suppress anti-tumor immunity and hamper the therapeutic response. Hypoxia mediates these effects by several potential mechanisms: altering gene expression, the activation of oncogenes, inactivation of suppressor genes, reducing genomic stability and clonal selection. We have reviewed the effects of hypoxia on tumor biology and the possible strategiesto manage the hypoxic tumor microenvironment (TME), highlighting the potential use of cancer stem cells in tumor treatment.

Association of serum and follicular fluid leptin and in vitro Fertilization/ ICSI outcome: A systematic review and meta-analysis.

There are conflicting reports regarding circulating leptin and its relationship between pregnancy outcomes in infertile women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). We performed a systematic review and meta-analysis to assess the association between serum or follicular fluid (FF) leptin concentrations reported for infertile women and their IVF outcome. A systematic search was undertaken in available databases (PubMed, Scopus, Web of Science, The Cochrane Library and Embase) to find studies published up to Aug 2020 and the standardized mean difference with 95 % confidence interval was taken from 14 eligible studies. Both graphical (funnel plots) and test methods (Egger's regression test and the Begg) assessed the presence of publication bias. Subgroup analysis was used to investigate the source of heterogeneity. Pooled effect sizes based on the eligible papers indicated that of there is no statistically significant correlation between leptin levels in follicular fluid and serum on the day of ovum pick-up (OPU) and day of HCG (human chorionic gonadotrophin) administration in pregnant and non-pregnant women who underwent IVF/ICSI cycles. However, combination of leptin in serum and/or FF with other parameters may be a useful marker to predict IVF outcome.