Free-fatty acid receptor-4 gene polymorphism (rs61866610) and colorectal cancer risk.

This study aimed to investigate the impact of Free-fatty acid receptor-4 (FFAR4) rs61866610 polymorphism on colorectal cancer (CRC) risk. Herein, ninety-two histopathologically confirmed CRC patients and 95 healthy individuals were evaluated for FFAR4 polymorphism by RFLP-PCR. Gender, age, body mass index (BMI), underlying disease, and smoking status were recorded for all subjects. Clinical and histopathologic findings including tumor grade and TNM stage were also prepared in the patient group. Except for type 2 diabetes which was more prevalent in the control group, there were no differences between the two groups regarding underlying diseases (p > 0.05). The frequency of genotypes was as follows: in the CRC group 75% wild type, 23.9% heterozygous, and 1.1% homozygous mutant. In the control group 85.3% wild type, 12.6% heterozygous, and 2.1% homozygous mutant. Mutant allele carriers were more frequent in CRC subjects (25%) than in the normal group (14.7%) but it did not reach a significant level. The frequency of mutant genotypes in colon cancer and rectal cancer was 27.5% and 8.3% respectively (p = 0.282). The mutant genotypes were found more in patients with high-grade tumors (p = 0.154). Subjects with stage III/IV had a higher frequency of mutant genotypes than low-stage cases (p = 0.011). No association was found regarding rs61866610 and obesity or type 2 diabetes (p > 0.05). In conclusion, FFAR4 (rs61866610) has no significant association with the risk of CRC, but the higher frequency of mutant genotypes in subjects with advanced cancer stages (III/IV) suggests further studies to determine the role of FFAR4 in colorectal tumorigenesis.

Effect of Melissa officinalis on Chemotherapy-Induced Peripheral Neuropathy in Cancer Patients: A Randomized Trial.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant cancer treatment side effect that can influence both quality of life and treatment course. Melissa Officinalis (MO), due to its high content of flavonoids, has antioxidant, anti-inflammatory, and neuroprotective properties.  Materials and Methods: The cancer patients diagnosed with CIPN attended a referral center in Sari (Iran). The hydroalcoholic extract of MO leaves was extracted by the maceration method. The control group received a placebo along with gabapentin as the standard treatment, and the intervention group received 500 mg Melissa officinalis 2 times daily for 3 months plus gabapentin. Patients were evaluated at the baseline and 3 months later, according to Common Terminology Criteria for Adverse Effects (CTCAE) and EORTC QLQ-C30 (Integrated System for Quality of Life Assessment).  Results: A total of 40 patients were considered as group D (intervention group), and 35 patients completed the study. Out of 40 subjects in the placebo group (P), 3 patients could not tolerate the drug due to gastrointestinal disturbances. The final values of CTCAE showed a statistically significant difference (p=0.010). Indicators related to the quality of life in both groups showed a significant improvement. In the intervention group, the pain perception and diarrhea experience were significantly reduced. Conclusion: Quality of life indicators were improved by prescribing gabapentin with and without Melissa officinalis. The addition of Melissa officinalis to the chemotherapy regimen may improve diarrhea and pain perception.

Evaluation of Circulating Leptin and Its Receptor (Ob-R) Tissue Expression in Colorectal Cancer, a Report From North of Iran.

Background & Objective: Leptin is an adipocyte-derived hormone with a critical role in energy balance. As demonstrated by previous investigations, leptin acts as a proliferative and angiogenic factor in cancer cells. However, results regarding its role in colorectal cancer are still inconclusive. We aimed to evaluate serum leptin and tissue expression of leptin receptor (Ob-R) in normal and malignant samples of colorectal. Methods: Serum and tissue samples from pathology-confirmed colorectal cancer patients and normal controls referring to a university hospital of Mazandaran were obtained during 2019-21. ELISA and immunohistochemistry were applied to determine leptin and Ob-R expression respectively. Results: A total of 90 samples belonging to 46 normal and 44 CRC patients were enrolled. Normal and CRC groups included 32 (69.56%) and 21 (47.72%) female subjects respectively. The average leptin concentration in the normal group was 115.80 and, in the patient, group was 124.47 ng/mL (P=0.897). CRC cases showed an insignificantly higher Ob-R detection rate (P=0.086). Conclusion: There was no significant difference in leptin and Ob-R expression between CRC patients and normal subjects. Thus, leptin and its receptor may not be useful as a biomarker of CRC.

Neutrophil-to-lymphocyte, platelet-to-lymphocyte and lymphocyte-to-monocyte ratios, any association with metabolic syndrome?

Background: Metabolic syndrome is a critical health concern associated with an elevated risk of chronic health problems including cardiovascular disease and diabetes. There are shreds of evidence that novel inflammatory ratios including neutrophil-to-lymphocyte, platelet-to-lymphocyte and lymphocyte-to-monocyte ratios serve as prognostic biomarkers for metabolic syndrome (MetS). This hypothesis was investigated in a cohort of the Iranian population. Methods: selection of MetS + subjects was based on the National Cholesterol Education Program Adult Treatment Panel III criteria 3 (NCEP ATP 3). The control group consisted of participants negative for any of the five MetS criteria. Demographic and laboratory data were extracted from the Tabari cohort study. Results: A total of 1930 subjects including 965 Mets positive and 965 MetS criteria negative participants were evaluated. Diabetes (84.8%), hypertension (48.9%), hypertriglyceridemia (81.7%), low HDL cholesterol (70.3%), and high waist circumference (78.9%) were observed in patients. There were no differences between NLR (1.66±0.71 vs. 1.69±0.72 P=0.42), LMR (11.23±3.13 vs. 11.30±11.99, P= 0.86) and PLR (113.85±68.67 vs 114.11±35.85, P=0.91) between case and control groups, respectively. Logistic regression analysis revealed no association between ratios and MetS risk even after adjusting for potential confounders including age, gender, living place, and BMI. Conclusion: In a relatively large population from Northern Iran, no association was observed between CBC-derived inflammatory ratios and the presence of MetS.

LGR5 As a Potential Therapeutic Target for Breast Cancer: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVE: Breast cancer is the world's most common malignancy. Despite significant advances in the diagnosis and treatment of the disease, the associated mortality rate is still high. Tumor initiating cells known as cancer stem cells with unique abilities are suspected responsible for therapy failure and poor prognosis. Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a cancer stem cell marker that promotes aggressive features in breast cancer cells. So, the aim of this study was to perform a systematic review and meta-analysis to evaluate LGR5 as a therapeutic target for breast cancer. METHODS: This systematic review and meta-analysis were performed using databases of Web of Science, Scopus, and PubMed. We searched these databases with LGR5 and Breast Cancer and related keywords based on the mesh database until Oct12, 2021. All studies that reported the rate of LGR5 high expression with Immunohistochemistry in breast cancer patients were included in this review. We used the STATA and random effect models for data analysis. RESULTS: Finally, 7 studies including 2632 breast cancer samples were studied. The pooled prevalence of LGR5 high expression in breast cancer was 48.6 % (CI95%: 40.5-56.7%, I2=0.0) and in triple negative was 48.6% (CI95%: 38.4-58.7%, I2= 0.0). CONCLUSION: Our findings show that the rate of LGR5 high expression in breast cancer in general and especially in triple-negative was considerable and it seems that this is a potential therapeutic target for breast cancer.

Association between Serum Progastrin Biomarker Level and Gastric Cancer.

BACKGROUND AND OBJECTIVE: gastric cancer is the fifth most prevalent cancer and the fourth cause of death because of cancer. In Iran, northern and northwestern regions are considered gastric cancer hot spots. Identifying serum biomarkers could be helpful in early diagnosis of patients with gastric adenocarcinoma (GAC). Increase in progastrin level has been reported in different cancers. Given the diagnostic value of this biomarker, this study aimed to determine the diagnostic role of progastrin serum biomarker in patients with gastric cancer. METHODOLOGY: In this case-control study, forty patients with gastric cancer who were diagnosed by endoscopy and pathologic findings and visited Mazandaran Comprehensive Cancer Center. The participants had received no treatment yet and entered this study. The participants in case group were compared with the control group including forty-two individuals with no history of gastrointestinal cancer in their first-degree relatives and visiting the lab for routine tests. Progastrin serum level was assessed using ELISA kit. The Kruskal-Wallis test and Mann Whitney test, both non-parametric) were used for statistical analysis and the relation between the variables was examined using Pearson's correlation coefficient at 95% confidence level in SPSS 16. FINDINGS: In this study, progastrin serum level was significantly higher in patients with gastric cancer compared with normal participants (P = 0.035). Progastrin serum level had no significant relation with tumor clinicopathologic parameters (p-value > 0.05). CONCLUSION: Increase in progastrin may be utilized as a predictive factor for gastric cancer.

TFF1 gene single nucleotide polymorphism (rs3761376) and colorectal cancer risk.

INTRODUCTION: Trefoil Factor 1 (TFF1) is a secretory peptide with gastrointestinal protective functions. Abnormal TFF1 expression is reported in some cancers and functional promoter polymorphism in TFF1 is believed to be associated with risk of gastric cancer. We evaluated rs3761376 in a sample of Iranian patients with colorectal cancer. METHODS: Peripheral blood samples were taken from pathology confirmed cases of colorectal cancer and healthy volunteers. Genotyping was carried out using Restriction Fragment Length Polymorphism (RFLP) PCR. Any association with clinicopathologic data was assessed by SPSS version 19. RESULTS: A total of 245 participants, including 122 patients with cancer and 123 non-cancer subjects were enrolled. Age, body mass index, and smoking habits were not significantly different between the two groups (P > 0.05). Distribution of TFF1 genotypes was not found to be associated with colorectal cancer. However, distant metastasis was more prevalent in carriers of the mutant allele. CONCLUSION: TFF1 rs3761376 was not associated with colorectal cancer but it may be involved in metastasis. Therefore, further investigation is warranted to determine this relationship.

Determining Serum Levels of IL-10 and IL-17 in Patients with Low Back Pain Caused by Lumbar Disc Degeneration.

BACKGROUND: Low Back Pain (LBP) is a common health problem that affects different aspects of a person's life. Degeneration of the intervertebral disc is a major cause of LBP. Interleukin- 17 (IL-17) is a pro-inflammatory cytokine. In contrast, interleukin-10 (IL-10) prevents the occurrence of immune over-stimulation by inhibiting inflammation. The purpose of this study was to evaluate the serum levels of these cytokines in LBP patients and in the control group. METHODS: In a case-control study, 87 patients, including 59 patients with low back pain and 28 healthy subjects, were examined after magnetic resonance imaging (MRI) approval. After recording demographic data, 5 ml of peripheral blood samples were obtained from the subjects, and enzyme- linked immunosorbent assays (ELISA) technique was performed to measure IL-10 and IL-17 in serum samples. All analysis was performed in the SPSS software version 20 at a significant level of 0.05. RESULTS: The case group consisted of 21 males and 38 females with mean age 49.6 yrs., and the control group consisted of 14 males and 14 females with a mean age of 36. The mean body mass index (BMI) was 26.5 in the patients and 25.4 in the control group (P>0.05). Serum levels of inflammatory cytokine IL-10 and IL-17 were significantly lower and higher in patients than controls, respectively (P=0.04, P=0.03). CONCLUSION: Differences in serum levels of IL-17 and IL-10 in the LBP group compared with the healthy group may indicate the role of inflammatory and autoimmune processes in causing disk damage. These findings could potentially be used by future studies to develop new LBP therapeutic strategies.

Association between pre-chemotherapy serum levels of vitamin D and clinicopathologic findings in gastric cancer.

BACKGROUND: To examine the serum levels of vitamin D in newly diagnosed gastric cancer (GC) patients compared with normal subjects and any possible association with prognostic variables. METHODS: One-hundred subjects (50 GC and 50 controls) were enrolled and serum vitamin D levels were assessed using ELISA. Based on two definitions, vitamin D was classified as a sufficient level (≥30 ng/dL) and optimal level (25-80 ng/dL). The χ2and unpaired t-test was used for data analysis with a significance level of 0.05. RESULTS: The mean serum levels of vitamin D in patients and controls were 26.86 (±14.6) and 31.72 (±13.4), respectively (P=0.09). The prevalence of vitamin D insufficiency and deficiency was higher in GC cases than controls (P=0.045 if sufficient level ≥30 and P=0.065 if sufficient level ≥25). According to histological grade analysis, grade 3 patients (poorly differentiated) were found with significantly lower vitamin D concentrations in serum than grade 1 and 2 subjects (22.25 vs 33.29 ng/dL, P=0.021). No significant differences were observed between the two groups in pathological tumor-node-metastasis (pTNM) stages, distant metastasis, and location of the tumor. CONCLUSION: Higher prevalence of vitamin D insufficiency and deficiency in GC patients may reflect its role in malignancy; however, further studies are needed to confirm this relationship and any possible benefits to the patients.

Up-regulation of human immune system function by Donkey's Milk

Donkey's milk represents a good alternative to human milk because of its chemical characteristics similar to those of human's. In present study, the pro- and anti-inflammatory effects of donkey's milk were evaluated on peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from 12 young and 12 aged normal subjects. PBMCs were cultured with or without the optimal and non-cytotoxic dose of pasteurized donkey's milk, and polymyxin B was used to inhibit the possible endotoxin contamination. Following 18 hours incubation, culture supernatants were harvested to measure the secreted Tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), Interleukin-8 (IL-8) and Interleukin-10 (IL-10) by ELISA. Donkey's milk significantly increased TNF-α (p= 0.01), IL-8 (p< 0.0001), IL-6 (p< 0.0001) and IL-10 (p= 0.01) levels in PBMCs. In addition, the levels of IL-6 (p= 0.002), IL-8 (p= 0.002) and TNF-α (p= 0.002) from aged subjects were significantly higher compared with young subjects. In contrast with these data, the level of IL-10 was markedly reduced from aged subjects (p= 0.02). Considering the immune-potentiation effects of donkey's milk, it is suggested investigating milk as a beneficial dietary component for up-regulating the immune response in aged people

TP53 single nucleotide polymorphism (rs1042522) in Iranian patients with coronary artery disease.

Chronic diseases including coronary artery disease (CAD) impose a high burden in terms of mortality and disability particularly in developing countries. Both genetic and environmental risk factors confer susceptibility to CAD. Meanwhile, a functional polymorphism in the tumor protein p53 (TP53) gene (codon 72, exon 4) has been reported to be associated with a wide range of cancers and inflammatory disorders. There are controversies regarding CAD and involvement of the TP53 codon 72 single nucleotide polymorphism; therefore, the present case-control study was conducted to evaluate the potential association between this TP53 polymorphism and CAD in an Iranian population. A total of 153 subjects (including 70 patients diagnosed with CAD and 83 subjects with normal coronary parameters, determined by angiography) were genotyped for the TP53 (rs1042522) polymorphism by the polymerase chain reaction-restriction fragment length polymorphism technique. Clinical and laboratory findings were also evaluated. The χ2 test and unpaired Student's t-test were applied to compare genotype and allele distributions and clinical characteristics between the two groups. Significant associations of the Pro72 allele [odds ratio (OR)=1.66, P=0.027] and Pro/Pro genotype (OR=2.91, P=0.022) with CAD were identified. No associations between patients' clinical findings and genotypes were apparent. Therefore, according to present findings, the TP53 Pro72 allele may be involved in the development of CAD along with conventional risk factors in patients from Northern Iran.

Association of P53 gene polymorphism with gastric cancer in Northern Iran as a high-risk region.

Gastric cancer has the fourth highest morbidity rate of all cancers worldwide. Genetic factors including alterations in oncogenes and tumor suppressor genes serve an important role in gastric cancer development and progression. The P53 gene acts as a tumor suppressor gene by regulating the cell cycle, DNA transcription and repair, apoptosis, senescence and genome stability. In addition to somatic P53 mutations in cancer development, germline polymorphisms are also involved in different malignancies. The polymorphism of P53 at codon 72 (Arg72Pro) is established as a common variant that increases susceptibility to various cancers. The present case-control study was conducted to evaluate the possible association between this P53 polymorphism and gastric cancer in the Iranian population. A total of 59 patients with gastric cancer and 59 healthy controls were enrolled in the present study. Genomic DNA was extracted from peripheral blood mononuclear cells and genotype analysis was performed using a polymerase chain reaction-based restriction fragment length polymorphism assay. Genotype frequencies did not differ significantly between the patients and controls (P=0.4); the frequencies of the three genotypes Arg/Arg, Arg/Pro and Pro/Pro in gastric cancer patients were 28.8, 49.2 and 22.0%, and in controls were 37.3, 49.2 and 13.6%. Additionally, there were no differences in genotype frequencies based on tumor location, histological differentiation or tumor stage. Based on these findings, it may be concluded that the P53 codon 72 polymorphism does not contribute to gastric cancer susceptibility in Northern Iran.

Anti-inflammatory effects of the Portulaca oleracea hydroalcholic extract on human peripheral blood mononuclear cells.

Background: Portulaca oleracea, known as Purslane, is an annual growing herb with wide distribution around the world and traditionally used to manage several diseases. Different therapeutic properties as an anti-fever agent as well as anti-inflammatory and analgesic effects have been attributed to P. oleracea. The aim of this study was to investigate the effects of P. oleracea aerial extract on production of pro- and anti-inflammatory cytokines by human peripheral blood mononuclear cells (PBMCs). Methods: Aerial parts of P. oleracea (stems and leaves) were collected and extracted by percolation using methanol. The optimal and non-cytotoxic dose of hydro-alcoholic extract for cell culture analysis was determined by MTT assay. To assess the antiinflammatory effects of P. oleracea, PBMCs obtained from 12 normal volunteers were cultured in RPMI complete medium and cotreated with E. coli lipopolysaccharide (LPS) and P. oleracea hydro-alcoholic extract. Following 18-hour incubation, culture supernatants were harvested for measurement of secreted TNF-α, IL-6 and IL-10 by ELISA. Statistical analyses were performed using the SPSS v.20, and data analyzed by Kolmogorov-Smirnov, Mann-Whitney U, Kruskal-Wallis and post Hoc tests. P-values<0.05 were considered significant. Results: The optimal non-cytotoxic concentration of P. oleracea aerial extract was defined as 100 µg/ml based on MTT viability assay. P. oleracea hydro-alcoholic extract significantly decreased the concentration of both pro-inflammatory cytokines TNF-α and IL-6 in LPS-stimulated PBMCs (p<0.001 and p<0.001, respectively). However, the concentration of IL-10 as an anti-inflammatory cytokine, did not show any statistically significant change (p=0.390). Conclusion: Our findings highlighted the potential anti-inflammatory properties of P. oleracea in herbal medicine. Future analysis on different constituents of total extract may confirm its therapeutic effects as a promising anti-inflammatory compound.