Anti-Cancer Effect of Dorema Ammoniacum Gum by Targeting Metabolic Reprogramming by Regulating APC, P53, KRAS Gene Expression in HT-29 Human Colon Cancer Cells.

Background: Colorectal cancer is a heterogeneous disease that leads to metabolic disorders due to multiple upstream genetic and molecular changes and interactions. The development of new therapies, especially herbal medicines, has received much global attention. Dorema ammoniacum is a medicinal plant. Its gum is used in healing known ailments. Studying metabolome profiles based on nuclear magnetic resonance 1HNMR as a non-invasive and reproducible tool can identify metabolic changes as a reflection of intracellular fluxes, especially in drug responses. This study aimed to investigate the anti-cancer effects of different gum extracts on metabolic changes and their impact on gene expression in HT-29 cell. Methods: Extraction of Dorema ammoniacum gum with hexane, chloroform, and dichloromethane organic solvents was performed. Cell inhibition growth percentage and IC50 were assessed. Following treating the cells with dichloromethane extract, p53, APC, and KRAS gene expression were determined. 1HNMR spectroscopy was conducted. Eventually, systems biology software tools interpreted combined metabolites and genes simultaneously. Results: The lowest determined IC50 concentration was related to dichloromethane solvent, and the highest was hexane and chloroform. The expression of the KRAS oncogene gene decreased significantly after treatment with dichloromethane extract compared to the control group, and the expression of tumor suppressor gene p53 and APC increased significantly. Most gene-altered convergent metabolic phenotypes. Conclusion: This study's results indicate that the dichloromethane solvent of Dorema ammoniacum gum exhibits its antitumor properties by altering the expression of genes involved in HT-29 cells and the consequent change in downstream metabolic reprogramming.

Larval therapy vs conventional silver dressings for full-thickness burns: a randomized controlled trial.

BACKGROUND: This is the first clinical trial to investigate the effectiveness of maggot debridement therapy (MDT) for full-thickness burn injuries in comparison to conventional silver dressings. METHODS: Thirty-one cases with full-thickness (grade III based on ICD-10 classifications version 2019) burns were assigned into larval therapy (15 cases) and conventional treatment (16 cases) groups. Participants in the MDT group have received loose larvae on days 0, 2, 4, and 6, while controls received a conventional regimen comprised of sharp debridement, silver sulfadiazine, antibiotic therapy, and offloading every day. The primary and secondary outcomes were defined as the time to debridement (from admission to skin autograft) and time to healing (from admission to complete healing post-skin autograft). Patients in two groups were also compared in terms of necrosis resolution, granulation, and granulation/necrosis (g/n) ratio during study time periods. RESULTS: Participants who received larvae had significantly decreased necrosis on days 2 (p = 0.028) and 4 (p = 0.023) compared to those who received control treatment. Significant differences (p < 0.001) were also observed for granulation between the two groups in favor of MDT and the fold changes of g/n in the larvae group were 5, 15, and 13 times higher than that for the conventional regimen on days 2, 4, and 6 of treatment, respectively. Strikingly, a subgroup analysis of high necrotic burns (necrosis > 50%) revealed a significant improvement (p < 0.001) for MDT compared to the control treatment. There were also significant differences (p < 0.001) for the time to debridement and time to healing between the two groups. However, bacterial contamination did not show significant changes between the two treatment regimens. CONCLUSIONS: Our findings revealed that MDT has a favorable superiority over conventional regimen for the treatment of grade-III burns, and thus further clinical trials with larger sample size are warranted to confirm these results.

The effects of nano-curcumin supplementation on Th2/tregulatory axis in migraine patients: a randomized, double-blind, placebo-controlled trial.

AIM: In the present study we aimed to investigate the effects of nano-curcumin supplementation on gene expression and serum levels of IL-4 and TGF-ß in migraine patients. METHODS: Forty participants with episodic migraine were randomly allocated to receive 80 mg nano-curcumin (n = 20) or placebo (n = 20) in a randomized double-blind clinical trial for two months. At the beginning and the end of the study, the interictal serum levels and gene expression of IL-4 and TGF-ß in peripheral blood mononuclear cells (PBMCs) isolated from migraine patients were measured, using ELISA and real-time PCR methods, respectively. RESULTS: Intra-group assays showed a significant rise in the gene expression of both IL-4 and TGF-ß (p < 0.05) in nano-curcumin group after two months of treatment, however the serum levels were only significantly changed for IL-4 (p < 0.05). On the contrast, inter-group assays revealed no statistical differences between nano-curcumin and placebo group in terms of IL-4 and TGF-ß gene expression, while the serum levels of IL-4 was observed to be increased significantly (p = 0.03) following two month nano-curcumin supplementation. CONCLUSION: The findings of the present trial suggest that the treatment with nano-curcumin could induce significant levels of IL-4, in favour of anti-inflammatory effects, while has a minimal effects on the both gene expression and serum levels of TGF-ß. Further studies are required to determine the exact mechanism of action of curcumin in patients with migraine.

The Effect of Oral Magnesium Supplementation on Inflammatory Biomarkers in Adults: A Comprehensive Systematic Review and Dose-response Meta-analysis of Randomized Clinical Trials.

This is a comprehensive systematic review and dose-response meta-analysis evaluating the effects of oral magnesium supplementation on inflammatory biomarkers including C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) among adults. The major databases including PubMed, Web of Science, Embase, and Google Scholar were searched for relevant publications until December 14, 2020, using appropriate keywords. The Cochrane Collaboration tool was used to assess the quality of each study. We also performed a subgroup analysis to identify probable sources of heterogeneity. A total of 18 studies with 927 participants fulfilled the eligibility criteria and included in this meta-analysis. Our results indicate that the supplementation with magnesium had no statistically significant effect on serum concentrations of CRP (WMD, - 0.49; 95% CI, - 1.72 to 0.75 mg/L; P = 0.44), IL-6 (WMD, - 0.03; 95% CI, - 0.40 to 0.33 pg/mL; P = 0.86), and TNF-α (WMD, 0.12; 95% CI, - 0.08 to 0.31 pg/mL; P = 0.24) compared with controls. In addition, based on dose-response assessment, no significant non-linear association was found between magnesium supplementation dosage or duration on serum CRP and IL-6 concentrations. The findings of the present systematic review and meta-analysis did not support the notion that oral magnesium supplementation could have favorable effects on CRP, IL-6, and TNF-α in the adult population.

A Metabolomic Investigation of Eugenol on Colorectal Cancer Cell Line HT-29 by Modifying the Expression of APC, p53, and KRAS Genes.

Colorectal cancer is one of the most lethal cancers with a high mortality rate. Chemotherapy results in drug resistance in some cases; hence, herbal medicines are sometimes used in adjunct with it. Eugenol has been reported to have anti-inflammatory, antioxidant, and anticancer properties. Metabolomics is a study of metabolic changes within an organism using high-throughput technology. The purpose of this research was to investigate the anticancer effects of eugenol and variations in p53, KRAS, and APC gene expression and metabolic changes associated with the abovementioned gene expressions using 1HNMR spectroscopy. The MTT method was used to determine cell viability and its IC50 detected. After treating HT-29 cells with IC50 concentration of eugenol, RNA was extracted and cDNA was obtained from them and the expression of p53, KRAS, and APC genes was measured using the qRT-PCR technique. Metabolites were extracted using the chloroform-ethanol method, lyophilized, and sent for 1HNMR spectroscopy using the 1D-NOESY protocol. Chemometrics analysis such as PLS-DA was performed, and differentiated metabolites were identified using the Human Metabolome Database. Integrated metabolic analysis using the metabolites and gene expression was performed by the MetaboAnalyst website. The observed IC50 for eugenol was 500 µM, and the relative expression of APC and p53 genes in the treated cells increased compared to the control group, and the expression of KRAS oncogene gene decreased significantly. The crucial changes in convergent metabolic phenotype with genes were identified. The results indicate that eugenol exhibits its antitumor properties by targeting a specific biochemical pathway in the cell's metabolome profile due to changes in genes involved in colon cancer.

The Effects of Magnesium Supplementation on Blood Pressure and Obesity Measure Among Type 2 Diabetes Patient: a Systematic Review and Meta-analysis of Randomized Controlled Trials.

In this study, we aimed to systematically review the literature to evaluate the effects of magnesium (Mg) supplementation on blood pressure (BP) and obesity measure among patients with type 2 diabetes mellitus (T2DM). Major electronic databases of Web of Science, the Cochrane library, PubMed, and Scopus were searched completely from the inception until 15 October 2019 to identify randomized clinical trials (RCTs) pertaining to the topic of interest. All outcomes were pooled using a random-effects model and expressed as weighted mean differences (WMD) with 95% confidential intervals (CI). Heterogeneity, sensitivity analysis, and publication bias were also assessed using standard methods. The pooled analysis of five RCTs showed that Mg supplementation did not affect body weight (WMD: - 0.01 kg, 95% CI: - 0.36 to 0.33), BMI (WMD: - 0.07, 95% CI: - 0.18 to 0.04), and waist circumference (WMD: 0.12, 95% CI: - 1.24 to 1.48) in T2DM patients compared to the control groups of the patients who received placebo. However, pooling seven RCTs together showed significant reduction of systolic blood pressure (WMD: - 5.78 mmHg, 95% CI: - 11.37 to - 0.19) and diastolic blood pressure (WMD: - 2.50 mmHg, 95% CI: - 4.58 to - 0.41) in T2DM patients. Furthermore, subgroup analysis by dose of intervention, intervention duration, and type of intervention suggested that Mg supplementation for > 12 weeks, in doses higher than 300 mg/day or inorganic forms, could significantly decrease both systolic and diastolic BP in T2DM patients. Based on the findings, Mg supplementation has beneficial effects on BP in type 2 diabetes patients independent of body weight status. However, further investigations are needed to provide more reliable evidences.

The effects of nano-curcumin supplementation on Th1/Th17 balance in migraine patients: A randomized controlled clinical trial.

BACKGROUND: The present study was aimed to evaluate the nano-curcumin supplementation on Th1/Th17 balance by assessment of gene expression and serum level of interferon gamma (IFN-γ) and interleukin-17 (IL-17) in migraine patients. METHODS: Forty participants with episodic migraine were randomly allocated to receive 80 mg nano-curcumin (n = 20) or placebo (n = 20) in a randomized double-blind clinical trial for two months. The expression of IFN-γ and IL-17 from peripheral blood mononuclear cells and IFN-γ and IL-17 serum levels were measured, using a real-time PCR and ELISA methods, respectively. RESULTS: Compared to placebo group, two month nano-curcumin supplementation led to a significant reduction in serum levels and expression of IL-17 mRNA (P = 0.006 & 0.04, respectively), while there was no statistical difference regarding serum levels and expression of IFN-γ mRNA. CONCLUSION: Nano-curcumin supplementation in migraine patients led to a significant reduction in gene expression and plasma levels of IL-17 compared to control group.

Effect of Rosa canina Distilled Water on Tamoxifen-treated Male Wistar Rats.

BACKGROUND AND OBJECTIVE: In spite of therapeutic effect of tamoxifen on the breast cancer, it has some side effects on the liver including non-alcoholic fatty liver disease. In this study the effects of Rosa canina distilled water on the tamoxifen-induced fatty liver and oxidative stress status in male rats were investigated. MATERIALS AND METHODS: Twenty four adult male Wistar rats were randomly divided into 4 groups of 6: 1st group: Untreated control rats (C), 2nd group (T): The rats received tamoxifen, 3rd group (T+R): Rats received tamoxifen and Rosa canina distilled water and 4th group (R): Rats received only Rosa canina distilled water. Tamoxifen at 1 mg kg-1/day was injected subcutaneously for 7 days and the rats received orally Rosa canina distilled water at 1 mL/rat/daily for 14 days. At the end of the study, animals were studied for serum biochemical parameters (glucose, lipid profile, BUN, creatinine, uric acid, urea, ALT, AST, ALP, total protein, bilirubin, oxidative stress indices, sperm analysis and histology of the liver. The data were analyzed with SPSS software version 20 and expressed as Mean±SD. RESULTS: Rosa canina distilled water improved liver enzyme and renal function indices which disturbed due to tamoxifen treatment. While tamoxifen enhanced lipid peroxidation, Rosa canina distilled water reduced it. In addition, tamoxifen reduced the mobility, morphology and viability of sperms, but the Rosa canina distilled water enhanced the sperm parameters. Histological results also confirmed the adverse effect of tamoxifen and the favorable impact of the Rosa canina distilled water on the liver structures of animals. CONCLUSION: Rosa canina distilled water could modulate tamoxifen-induced fatty liver as well as improving the sperm parameters.

Alterations in serum levels of trace element in patients with breast cancer before and after chemotherapy.

BACKGROUND: Breast cancer is the most common serious disease around the world. The trace elements have a vital role in the metabolism and chemotherapy may change the level of metal ions. Due to the ambiguity of the existence in this regard, the study examined the trace element serum levels in women with breast cancer before and after chemotherapy . METHODS: Sixty patients were studied undergoing specialist. First sampling was taken before chemotherapy (after 4 weeks of surgery) and second sampling was taken after the completion of 3 courses of chemotherapy, approximately 9 weeks after the first chemotherapy. The patients took Adriamycin 60mg/m2 Cytoxan 600mg/m2. Serum zinc and iron levels were measured using standard spectrophotometric method. Measurement of serum copper was done by atomic absorption spectroscopy. RESULTS: Serum zinc and iron levels in women after chemotherapy significantly decreased (p<0.001), however, the serum level of copper increased but was not significant (P=0.676). CONCLUSIONS: Our findings demonstrate significant decrease in zinc and iron levels in breast cancer patients after 3 courses of Adriamycin and Cytoxan chemotherapy. Prescribing zinc supplements can be useful after chemotherapy.

Proposed radiological criteria for pre-operative determination of resectability in peritoneal-based malignancies.

BACKGROUND: The selection of patients for cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy infusion (HIPEC) is important, and relies heavily on imaging. However, it has been reported that Computer Tomographic (CT) scans may only achieve a low sensitivity of 33% for peritoneal disease. We propose a set of radiological criteria for pre-operative determination of resectability of peritoneal disease in peritoneal-based malignancies and validate this in our cohort of patients. METHODS: A retrospective review of all patients who underwent laparotomy with a view for CRS and HIPEC, at the National Cancer Centre Singapore from January 2000 to April 2010, was performed. Intra-operative Peritoneal Cancer Index (PCI) scores were recorded. The pre-operative imaging was reviewed with a senior radiologist who was blinded, and recorded the radiological PCI scores (CT-PCI) and eight additional CT prognostic factors (CT-PF). The CT-PCI and CT-PF scores were then compared with the intra-operative findings to determine the radiological accuracy. The scores and the individual prognostic factors were then evaluated for their predictive ability for unresectability. RESULTS: Comparison of the CT-PCI and PCI scores showed a concordance correlation coefficient at 0.52 (95% CI 0.34-0.7). Accuracy was increased with the addition CT-PF. The presence of omental caking and ascites were predictors of unresectability. We propose a scoring system which is able to predict for unresectable disease with a specificity of 80% and a sensitivity of 62%. CONCLUSION: With our proposed criteria, and scoring system, the selection of patients for CRS and HIPEC can be improved, and unnecessary exploratory operations avoided.