Decreased expression of p53 is associated with down expression of zyxin in breast cancer.

Background and Aims: Breast cancer (BC) is considered one of the most common malignant tumors leading to death in women, and genetic factors have a crucial role in BC pathogenesis. Zyxin (ZYX) is one of these factors that may be important in p53 level and function. Thus, the present work aimed to investigate the ZYX gene and protein expression in tumor tissue and matched margin tissue and its correlation with the p53 expression. Methods: In a present case-control study, 30 tumors and 30 matched margin tissues were obtained from Iran Tumor Bank/Tehran University of Medical Sciences. Real-time polymerase chain reaction and western blot analysis techniques were applied to evaluate the genes and protein expression, respectively. Results: The data showed that expression of the ZYX gene in tumor tissues significantly decreased (p = 0.0274) compared to matched margin tissues. In contrast, the p53 gene expression in tumor tissues had no significant difference with matched margin tissues. Additionally, we observed that ZYX and p53 genes expression in tumor tissues of estrogen receptor-positive patients had significant elevation than estrogen receptor-negative patients (p < 0.001, p < 0.001, respectively). The data of the western blot analysis technique showed that protein expression of ZYX (p = 0.0024) and P53 protein (p = 0.0218) in tumor tissues was significantly reduced compared to matched margin tissues. Additionally, our analysis showed a direct and significant correlation between the expression of ZYX and p53 proteins (r = 0.7797, p = 0.0126) and expression of ZYX and p53 genes (r = 0.3079, p = 0.0187). Conclusion: Based on our observation, ZYX might have a tumor suppressor role and is associated with p53.

Improvement photothermal property of MoS2/Fe3O4/GNR nanocomposite in cancer treatment.

The objective of the present study was to develop a novel molybdenum disulfide/iron oxide/gold nanorods (MoS2/Fe3O4/GNR) nanocomposite (MFG) with different concentrations of AgNO3 solution (MFG1, MFG2, and MFG3) for topical doxorubicin (DOX) drug delivery. Then, these nanocomposites were synthesized and characterized by Fourier transform infrared (FTIR), Transmission electron microscopy (TEM), Dynamic light scattering (DLS), and Ultraviolet-visible (UV-Vis) spectroscopies to confirm their structural and optical properties. Cytotoxicity of samples on Hela cell was determined using MTT assay. Results indicated that nanocomposites possess little cytotoxicity without NIR laser irradiation. Also, the relative viabilities of Hela cells decreased when the concentration of AgNO3 solution increased in this nanocomposite. Using NIR irradiation, the relative viabilities of Hela cells decreased when the concentration of samples increased. Acridine orange/propidium iodide (PI) staining, flow cytometry were recruited to evaluate the effect of these nanocomposites on apoptosis of Hela cells. Finally, results revealed when DOX loading increased in nanocomposite, then cell viability was decreased in it. Therefore, these properties make MFG3 nanocomposite a good candidate for photothermal therapy and drug loading.

The silibinin-loaded Zein-ß cyclodextrin nano-carriers (SZBC-NCs) as a novel selective cancer cell drug delivery system in HT-29 cell line.

Entrapping phytochemical bioactive compounds into nano-structured biocompatible polymers has been successfully utilized for improving cancer treatment efficiency. Silibinin is a potent compound that shows promising anticancer properties. In the present study, the Zein-ß-cyclodextrin complex was used to encapsulate silibinin and evaluate the induced cell death type and cytotoxic impacts on human cancer cells. The silibinin-loaded Zein-ß cyclodextrin nano-carriers (SZBC-NCs) were synthesized utilizing a gradual ultrasound-mediated homogenization technique and characterized by Zeta potential, DLS, FESEM, and FTIR analysis. The SZBC-NCs' antioxidant activity was studied by conducting ABTS and DPPH radical scavenging assays. Finally, the SZBC-NCs selective toxicity and cellular death induction mechanism were studied on the HT-29 and AGS cancer cells by measuring the cell survival and apoptotic gene (Caspase 3, 9), respectively, which were verified by conducting the DAPI staining analysis. The negatively charged (- 27.47 mV) nanoparticles (286.55 nm) showed significant ABTS and DPPH radical scavenging activity. Moreover, the remarkable decrease in the IC50 concentrations of the SZBC-NCs among the HT-29 and AGS cancer cell lines exhibited their selective cytotoxic potential. Also, the overexpressed apoptotic (Caspases 3 and 9) and down-regulated necrotic (NFKB) gene expressions following the SZBC-NCs treatment doses indicated the apoptotic activity of SZBC-NCs, which were verified by the increased apoptotic morphology of the DAPI-stained HT-29 cancer cells. The antioxidant and colon cancer cell-related apoptotic activity of the SZBC-NCs make it an appropriate anti-colon cancer nano delivery system. Therefore, they can potentially be used as a safe efficient colon cancer treatment strategy. However, further in vivo experiments including animal cancer models have to be studied.

The Lawson-loaded ß-cyclodextrin nanocarriers (LB-NCs) a novel targeted cancer cell in stomach and breast cancer as a drug delivery system.

Applying nanotechnology to design drug delivery systems is a promising turning point in cancer treatment strategies. In the current study, Lawson, a nonpolar anticancer phytochemical, was entrapped into ß-cyclodextrin polymer to evaluate its selective cytotoxicity in several types of human cancer cell lines including MCF-7, AGS, A549, and PC3. The Lawson-loaded ß-cyclodextrin nanocarriers (LB-NCs) were produced by applying a high-energy ultrasound-mediated homogenization technique. The LB-NCs were characterized by applying dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), zeta potential, and field emission scanning electron microscopy (FESEM) analysis. Also, the selective cytotoxic impact of the LB-NCs was studied by conducting the MTT assay on human MCF-7, AGS, A549, and PC3 cancer cell lines. Finally, the type of cellular death was evaluated by measuring the cell cycle status and apoptotic gene expression profile of the treated MCF-7 cells by conducting flow cytometry and Q-PCR methods, respectively. The synthesized negatively charged (- 23.8 mV) nanoparticles (348.12 nm) exhibited apoptotic activity in the human breast MCF-7 cancer cells by upregulating the apoptotic gene expression profile (Caspase 3, 8, and 9). The LB-NCs exhibited a significant selective cytotoxic effect on the human cancer cell lines compared with the normal HUVEC cells. However, variable toxic intensities were detected depending on the cancer cell type. Selective cancer cell-depended anticancer activity of the produced LB-NCs has the potential to be considered their safe efficient targeted anticancer activity. However, studying the animal cancer models has to be conducted to verify their selective toxicity and clarify the cellular death mechanism.

Preparation of the Myricetin-Loaded PEGylated Niosomes and Evaluation of their in†vitro Anti-Cancer Potentials.

Several edible plants contain flavonoids, including myricetin (Myr), which perform a wide range of biological activities. Myr has antitumor properties against various tumor cells. In this study Myr-loaded PEGylated niosomes (Myr-PN) were prepared and their anti-cancer activities were evaluated in vitro. Myr-PNs were prepared as a tool for drug delivery to the tumor site. Myr-PN was characterized in terms of size, zeta potential, and functional groups using dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), and field emission scanning electron microscopy (SEM). The Myr-PN size was 241 nm with a polydispersity index (PDI) of 0.20, and zeta potential -32.7±6.6 mV. Apoptotic properties of Myr-PN against normal and cancer cell lines were determined by flow cytometry and real-time quantitative PCR. Cancer cells showed higher cytotoxicity when treated with Myr-PN compared with normal cells, indicating that the synthesized nanoparticles pose no adverse effects. Apoptosis was induced in cells treated with 250 µg/mL of Myr-PN, in which 45.2 % of cells were arrested in subG1, suggesting that Myr-PN can induce apoptosis. In vitro, the synthesized Myr-PN demonstrated potent anticancer properties. Furthermore, more research should be conducted in vitro and in vivo to study the more details of Myr-PN anti-cancer effects.

Novel formulation of parthenolide-loaded liposome coated with chitosan and evaluation of its potential anticancer effects in vitro.

BACKGROUND: In this study the formulation of parthenolide (PN), an anticancer agent extracted from a natural product, into a liposome (PN-liposome), was examined. The surface of the PN-liposome was modified using chitosan (PN-chitosome). By using real-time quantitative PCR and flow cytometry, we examined the release of PN-chitosomes, cytotoxicity, and ability to induce apoptosis in vitro. METHODS AND RESULTS: According to the present study, PN-chitosomes had a size of 251 nm which is acceptable for efficient enhanced permeation and retention (EPR) performance. PN-chitosomes were confirmed to be spherical in shape and size through FESEM analysis. In terms of encapsulation efficiency, 94.5% was achieved. PN-chitosome possessed a zeta potential of 34.72 mV, which was suitable for its stability. According to the FTIR spectra of PN and PN-chitosome, PN was chemically stable due to the intermolecular interaction between the liposome and the drug. After 48 h, only 10% of the PN was released from the PN-chitosome in PBS (pH 7.4), and less than 20% was released after 144 h. CONCLUSION: In a dose-dependent manner, PN-chitosome exhibited anticancer properties that were more cytotoxic against cancer cells than normal cells. Moreover, the formulation activated both the apoptosis pathway and cytotoxic genes in real-time qPCR experiments. According to the cytotoxicity and activating apoptosis of the prepared modified particle, PN-chitosome may be helpful in the treatment of cancer.

A novel nanoformulation of parthenolide coated with polydopamine shows selective cytotoxicity and induces apoptosis in gastric cancer cells.

An anticancer agent derived from a natural product, parthenolide (PN), was studied to formulate PN into poly(lactic-co-glycolic acid) (PLGA). Polydopamine (PDA) was employed to modify the surface of PN-PLGA. Following characterization, the PN-PLGA-PDA was evaluated for its in vitro release, cytotoxicity, and ability to induce apoptosis using flow cytometry and real-time quantitative PCR. According to the present study, PN-PLGA-PDA had a size of 195.5 nm which is acceptable for efficient enhanced permeation and retention (EPR) performance. The SEM results confirmed the size and spherical shape of the nanoparticles. The percentage of encapsulation efficiency was 96.9%. The zeta potential of PN-PLGA-PDA was - 31.8 mV which was suitable for its stability. FTIR spectra of the PN-PLGA-PDA indicated the chemical stability of the PN due to intermolecular hydrogen bonds between polymer and drug. The release of PN from PN-PLGA-PDA in PBS (pH 7.4) was only 20% during the first 48 h and less than 40% during 144 h. PN-PLGA-PDA exhibited anticancer properties in a dose-dependent manner that was more cytotoxic against cancer cells than normal cells. Moreover, real-time qPCR results indicated that the formulation activated apoptosis genes to exert its cytotoxic effect and activate the NF-kB pathway. Based on our findings, PN-PLGA-PDA could serve as a potential treatment for cancer.

Relationship Between Human FCγRIIA rs1801274 G Allele and Risk of Death Among Different SARS-CoV-2 Variants.

Coronavirus disease 2019 (COVID-19), the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 and spread very quickly across the world. Different responses to infections have been related to fragment crystallizable gamma-receptor II alpha (FcγRIIA) polymorphisms. The purpose of this investigation was to determine if FCγRIIA rs1801274 polymorphism was related to COVID-19 mortality among different variants of SARS-CoV-2. The FCγRIIA rs1801274 polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism technique in 1,734 recovered and 1,450 deceased patients. Deceased patients had significantly higher minor allele frequency of the FCγRIIA rs1801274 G allele than in the recovered cases. The COVID-19 mortality was associated with FCγRIIA rs1801274 GG and AG genotypes in the Delta variant and with FCγRIIA rs1801274 GG genotypes in the Alpha and Omicron BA.5 variants. The reverse transcription-quantitative polymerase chain reaction Ct values revealed statistically significant differences between individuals with a G allele and those with an A allele. In conclusion, among the several SARS-CoV-2 variants, there may be a correlation between the mortality rate of COVID-19 and the G allele of FCγRIIA rs1801274. To confirm our findings, thorough research is still required.

Effects of curcumin and metformin on oxidative stress and apoptosis in heart tissue of type 1 diabetic rats.

Introduction: Hyperglycemia enhances oxidative stress and apoptosis and induces damages in heart tissue. Based on antioxidant properties of curcumin and metformin, we hypothesized that these agents may exhibit cardioprotective effects by attenuating oxidative stress and modulating expression of the genes involved in apoptosis in type-1 diabetes. Methods: Thirty-six male rats were randomly divided into six groups; (N): control; (D): streptozotocin-induced diabetic rats; (D+Cur50) and (D+Cur150): diabetic rats treated with 50 and 150 milligram of curcumin per kilogram of body weight (mg/kg.bw), respectively; (D+Met300) and (D+Met500): diabetic rats received 300 and 500 mg/kg.bw of metformin, respectively. Heart tissues were dissected and gene expression levels of Bax, Bcl-2, and caspase-3 were analyzed. Total anti-oxidant capacity (TAC), total oxidant status (TOS), and malondialdehyde (MDA) level, and activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured. Results: Enhancement in TOS, OSI, and MDA levels as well as increased in the activity of CAT and reduction in SOD and GPx activities were observed in diabetic group (D) compared with control rats. Treatment of diabetic animals with either curcumin or metformin normalized TOS, OSI, and MDA levels and restored CAT, SOD, and GPx activities. Diabetes caused extensive damages in heart tissue of rats (group D) and increased expression of caspase-3 and Bax genes and enhanced ratio of Bax/Bcl-2 expression compared with controls. Treatment with curcumin or metformin mitigated histopathological changes and dampened apoptosis by normalizing Bax and caspase-3 expression. Conclusion: Curcumin and metformin modulated diabetes-induced cardiac damage probably by reducing oxidative stress.

The effects of metformin monotherapy and combination of metformin and glibenclamide therapy on the expression of RAGE, Sirt1, and Nrf2 genes in peripheral blood mononuclear cells of type 2 diabetic patients.

Purpose: Although metformin is the first-line treatment of type 2 diabetes mellitus (T2DM), a few studies have evaluated the benefits of monotherapies (metformin) versus combination therapy (metformin and glibenclamide) for treatment of T2DM patients. The present study aimed to evaluate the effect of monotherapy with metformin compared to combination therapy with metformin and glibenclamide on the expression of RAGE, Nrf 2, and Sirt1genes. Methods: EightyT2DM patients and 40 healthy individuals participated in this case-control study. The patients in the treatment group were divided into two groups who received either metformin alone (n = 40) or metformin in combination with glibenclamide (n = 40). FBS, HbA1c, and fructosamine were measured. The expression of RAGE, Nrf 2, and Sirt 1 genes in PBMC of all subjects were assessed using real-time PCR. Results: RAGE gene expression in both treatment groups was significantly lower than the control (P < 0.05). RAGE gene expression was significantly reduced in the combination of metformin and glibenclamide treated group compared to metformin group (P < 0.05). Additionally, the expression of Sirt 1 and Nrf 2 genes in both treatment groups was higher than that of the control group (P < 0.05). The expression of Sirt 1 and Nrf 2 genes in metformin and glibenclamide treated group were higher than the metformin group (P < 0.05). Conclusion: Combination therapy (metformin and glibenclamide) showed stronger effect on repression of the RAGE gene and activation of Nrf 2 and Sirt 1 genes compared to monotherapy (metformin); therefore, it can be concluded that combination therapy may have more protective effects on the T2DM patients. No significant correlation was observed between HbA1c and RAGE, Sirt 1, and Nrf 2 genes expression.

Hyaluronic acid-coated chitosan nanoparticles as targeted-carrier of tamoxifen against MCF7 and TMX-resistant MCF7 cells.

Tamoxifen (TMX) is used to treat hormone-receptor-positive breast cancers at early stages. This research aimed to assess the potential of NPs in targeted delivery of TMX against MCF7 and TMX-resistant MCF7 breast cancer cell lines. For this purpose, a targeted delivery system including chitosan NPs coated with hyaluronic acid (HA-CS NPs) was created and examined in vitro. Chitosan NPs were first fabricated and loaded with TMX using the ionic-gelation method to prepare a drug-delivery system. Then, TMX-loaded CS NPs were coated by crosslinking the amino groups of chitosan to the carboxylic group of hyaluronic acid. The developed TMX delivery system was then optimized and characterized for particle fabrication, drug release, and targeting against cancer cells. The HA-CS particle size was 210 nm and its zeta potential was +25 mv. The encapsulation efficiency of TMX in NPs was 55%. TMX released from the NPs in acidic pH (5-6) was higher than the physiological pH (7.4). The cytotoxic effect of TMX-loaded HA-CS NPs on MCF7 and TMX-resistant MCF7 cells was significantly higher than TMX-loaded CS NPs and free drug. The findings confirmed the significant suppressive impact of TMX-loaded HA-CS NPs on MCF7 and TMX-resistant MCF7 cancer cells compared to the TMX-loaded CS NPs and free TMX. Graphical abstract.

TLR2 and TLR4 Signaling Pathways and Gastric Cancer: Insights from Transcriptomics and Sample Validation

Background: Pattern recognition receptors, especially toll-like receptors (TLRs), as the first line of defense for pathogen detection, were found to be associated with H.¬ pylori infection and gastric cancer (GC). However, the expression levels of TLRs, i.e. TLR2 and TLR4, as the main receptors sensed by H.¬ pylori, still remain largely ambiguous. We aimed to investigate the patterns of key transcripts of TLR2 and TLR4 in 100 GC transcriptome data. Additionally, we evaluated TLR2 and TLR4 gene expressions in gastric biopsies of Iranian GC patients, in order to validate RNA-seq outputs. Methods: For this study, 100 runs of GC samples and controls were processed and analyzed using map read to reference. Differential gene expression method was used to distinguish between GC and normal samples in the expression of TLRs and other innate immune molecules. Also, using qRT-PCR assay, transcripts of TLRs molecules for 15 GC and 15 control samples were analyzed based on the analysis of variance and least significant differences. Results: The results clearly showed that all signaling pathways molecules of TLR4, especially TLR4 (p = 0.019), NF-κB (p ¬= 0.047), IL-1ß (p = 0.0096), and TNF-α (p = 0.048), were upregulated in a cancerous condition in different parts and at various stages of GC. Conclusion: Our findings suggested that molecules involved in inflammation, including TLR4 and its related pro-inflammatory cytokines, may be responsible for the development and progression of GC. Accordingly, the control of H. pylori infection reduces inflammation in the gastric system and can play an important role in preventing gastrointestinal disorders.

Adiponectin gene polymorphisms and risk of type 2 diabetes: an updated evidence for meta-analysis.

BACKGROUND: Growing body of evidence suggest the association between SNP - 11377 C > G and SNP + 276 G > T polymorphisms of adiponectin gene with type 2 diabetes (T2D). However, these findings have not been conclusive and consistent. The present study quantitatively evaluates the data on the association between DIPOQ - 11377C/G, and + 276G/T polymorphisms and risk of T2D through a meta-analysis. METHODS: A systematic search was performed in the PubMed, Web of science, Scopus and Cochrane library databases to extract published studies according to the inclusion criteria. Among the 741 studies, 391 of them were screened as full text and 31 studies were finally included in the meta-analysis. Analysis of data was performed using random-effects model. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to analyze the strength of association. Subgroup and meta-regression analyses were performed to identify the potential source of heterogeneity. RESULTS: The pooled analysis showed that there was no statistically significant association between genotypes of CC (OR = 0.76, 95% CI: 0.53-1.09, P = 0.14), CG (OR = 0.93, 95% CI: 0.72-1.20, P = 0.58) and GG (OR = 1, 95% CI: 0.80-1.26, P = 0.94) ADIPO - 11377 polymorphism with increased risk of T2D. In addition, the results revealed a trend toward an increased risk of T2D for the SNP + 276 TT genotype (OR = 0.87, 95% CI: 0.77-0.98, P = 0.026) as compared with the GT and GG genotypes. Subgroup analysis by ethnicity indicated significant association between the TT genotype of the SNP + 276 and increased risk of T2D among Europeans. Met-regression demonstrated significant association between the GT genotype of + 276 polymorphism with risk of T2D in male individuals (slope: 0.0006; 95% CI: 0.0002-0.0009; P < 0.001). CONCLUSIONS: Collectively, our findings demonstrated a positive association between ADIPOQ + 276 G > T polymorphism with increased risk of T2D in male individuals with European ethnicity.

Impacts of garlic extract on testicular oxidative stress and sperm characteristics in type 1 and 2 diabetic rats: An experimental study.

BACKGROUND: Hyperglycemia damages various tissues such as the testes through oxidative stress and inflammation, which can eventually lead to infertility. OBJECTIVE: Garlic extract effects on the testicular tissue of diabetic rats were investigated. MATERIALS AND METHODS: In this experimental study, 36 male Wistar rats (8-wk old, weighing 230-300 gr) were randomly divided into 6 groups (n = 6/each) including; C: control rats, G: received 0.4 gr of garlic extract/100 gr body weight, D1: Streptozotocin-induced-diabetic rats or type 1, D1+G: D1 rats that were treated with garlic, D2: Streptozotocin + nicotinamide-induced-diabetic rats or type 2, D2+G: D2 rats treated with garlic. At the end of the study, serum testosterone was assayed by ELISA. Also, sperm quality and quantity were evaluated. For determination of oxidative stress status, total antioxidant capacity, total oxidative status, lipid peroxidation, and thiol groups were assayed in the testis tissues of the rats by colorimetric methods. Also, inducible nitric oxide synthase (iNOS) gene expression and the protein level of interleukin-1 ß (IL-1 ß ) were determined by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: In diabetic rats, glucose, total oxidative status and lipid peroxidation, iNOS gene expression, and IL-1 ß were higher than in non-diabetic rats, whereas testosterone, total antioxidant capacity and thiol groups, and sperm quality were significantly lower compared with control rats. These alterations were normalized by garlic intervention. CONCLUSION: In diabetic rats, garlic was associated with reduced glucose, oxidative stress, IL-1 ß , and iNOS gene expression and increased testosterone and sperm quality. So, the results suggest that garlic can reduce the severity of damage in testicular tissues of diabetic rats through its hypoglycemic, antioxidant, and anti-inflammatory properties.

Favorable effects of Anethum graveolens on liver oxidative stress and cholesterol 7 alpha-hydroxylase levels in non-alcoholic fatty liver disease (NAFLD) rat models.

BACKGROUND: High-fat high-cholesterol diet induces a phenotype similar to non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) in humans. In NAFLD and NASH, cholesterol and bile acid metabolisms are impaired to accumulate lipids and toxic bile acids along with cholestatic hepatic damage. Recently, the use of herbal-derived cholesterol lowering products has attracted much attention as possible therapeutic strategies for NAFLD. Hence, the aim of this study was to determine the effects of an Anethum graveolens (dill) on liver cholesterol 7 alpha-hydroxylase and liver fat accumulation in rats. METHOD: Thirty-six rats were randomly divided into 6 groups (n = 6) and received normal diet (ND) or a mixture of chow diet+2% cholesterol+0.5% cholic acid + 20% corn oil as high cholesterol/fat (HC-HF) diet (NAFLD model). Animals were also treated daily with dill tablet or dill extract (300 mg/kg). At the end of the 30 days experiments, serum and liver lipid profile and liver total antioxidant capacity were determined. Cholesterol 7 alpha-hydroxylase mRNA and protein expression levels were determined in the liver and histopathological changes in liver tissues were analyzed by microscope. RESULTS: Lipid profiles significantly decreased in dill treated groups (p < 0.05). Liver total antioxidant capacity significantly (p < 0.05) increased and MDA levels markedly (p < 0.05) reduced both in dill tablet and dill extract treated groups (p < 0.05). Both types of treatments caused significant increases in liver cholesterol 7 alpha-hydroxylase gene expression (p < 0.05). Histopathological examinations showed that treatment with dill normalized the hypercholesterolemia-induced changes in liver histology. CONCLUSION: Administration of dill significantly reduced liver fat, oxidative stress and increased cholesterol 7 alpha-hydroxylase enzyme at the both mRNA and protein levels. Dill extract was found more effective than its commercially available tablet.

Association of ADIPOQ rs266729 and rs1501299 gene polymorphisms and circulating adiponectin level with the risk of type 2 diabetes in a population of Iran: a case-control study.

PURPOSE: Mutation in various regions of the adiponectin (ADIPOQ) gene is described to be associated with type 2 diabetes (T2D). Our aim was to investigate the association between rs1501299 (SNP + 276 G > T) and rs266729 (SNP-11377 C > G) polymorphisms of ADIPOQ gene and susceptibility to T2D in an Iranian population. METHODS: This is a case-control study. A total of 210 subjects including 100 patients with T2D and 110 healthy controls were selected from an Iranian population. SNP-11377 C > G and SNP + 276 G > T polymorphisms were investigated using the Tetra ARMS-PCR method. RESULTS: The genotypes frequency of the SNP-11377 C > G polymorphism (P = 0.21) and SNP + 276 G > T polymorphism (P = 0.10) were in agreement with the Hardy-Weinberg equilibrium. The genotype and allele frequencies for rs266729 polymorphism showed a significant difference between the T2D and control groups. Further, the frequencies of the genotypes of GG (OR = 2.43, P = 0.031), GG + GG (OR = 2.11, P < 0.01) and G allele (OR = 1.6, P = 0.041) in SNP-11377 C > G polymorphism was significantly associated with an increased risk of T2D compared to control group. While, there was no significant association between the different genotypes of SNP + 276 G > T polymorphism and the risk of T2D in an Iranian population. The circulating adiponectin level in T2D subjects had significant difference compared to the control group in rs266729 polymorphism. CONCLUSION: We concluded that ADIPOQ rs266729 (SNP-11377 C > G) gene polymorphism but no rs1501299 is associated with increased risk of T2D in our population.

Clinicopathological, Immunohistochemical, and PMS2 Gene Expression Profiling of Patients with Sporadic Colorectal Cancer.

BACKGROUND: The DNA mismatch repair (MMR) system is one of the molecular pathways involved in colorectal cancer (CRC) carcinogenesis that consists of several genes, including MLH1 (MutL homolog 1), MSH6 (MutS homolog 6), MSH2 (MutS homolog 2), and MSH3 (MutS homolog 3). The protein encoded by PMS2 (post-meiotic segregation 2) is also essential for MMR. Here, we address the correlation between immunohistochemical and transcriptional expression of PMS2 with the tumor grade and clinical stage of non-hereditary/sporadic CRC disease. METHODS: This study retrospectively analyzed 67 colorectal resections performed for 38 male and 29 female patients. Random biopsies were taken by a gastroenterologist from patients referring to three hospitals in the cities of Zanjan, Urmia and Qazvin (Iran) during 2017-2019. All specimens were examined and classified for localization of tumor, pathological stage and grade. The PMS2 protein expression was studied immunohistochemically and analysis of mRNA expression was performed in the same tissue sections. RESULTS: Immunohistochemistry and quantitative real-time polymerase chain reaction (PCR) analysis showed a decrease in PMS2 expression compared with paracancerous tissue (P<0.001), which correlated with tumor stage. In addition, reduced PMS2 expression was correlated with the tumor differentiation grade, underlining a connection between downregulation of PMS2 and progression of CRC. Comparing the PMS2 mRNA levels in different groups showed the following results: 0.92 ± 0.18 in patients with Stage I CRC tumor, 0.86 ± 0.38 in Stage Ⅱ, 0.50 ± 0.29 in Stage Ⅲ, and 0.47 ± 0.23 in Stage Ⅳ. CONCLUSION: These findings suggest that PMS2 may provide a potential reliable biomarker for CRC classification by combined immunohistochemical and mRNA analysis.

Comparison of Salivary Antioxidants and Oxidative Stress Status in Gestational Diabetes Mellitus and Healthy Pregnant Women.

BACKGROUND: One of the most common complications of pregnant women is gestational diabetes mellitus (GDM). Oxidative stress can play an important role in GDM. OBJECTIVE: The aim of this study was to evaluate salivary antioxidants and oxidative stress markers in GDM. METHODS: Twenty pregnant women with GDM and 20 healthy pregnant women with normal blood glucose test participated in this study. Five mL of unstimulated saliva samples were collected. Spectrophotometric assay was carried out for sialo-chemical analysis. Stata software was used for data analysis. RESULTS: The GDM group exhibited no significant difference in salivary total antioxidant capacity and malondialdehyde compared to the healthy control group. All antioxidants markers, the uric acid, total antioxidant, peroxidase and catalase, decreased in GDM group that the difference of peroxidase and catalase was statistically significant. All of oxidative stress markers, the salivary malondialdehyde, total oxidative stress and total thiol, increased in GDM group. GDM group exhibited significantly higher salivary total oxidative stress levels. CONCLUSION: Catalase level was significantly lower and total oxidative stress was significantly higher. These two markers might have significant importance and might exhibit early changes compared to other factors in GDM. Some salivary antioxidants might have diagnostic, prognostic or therapeutic implications in GDM. Other studies with large sample size on salivary and blood samples need to be done to confirm these properties and salivary samples using instead of blood samples in GDM biomarkers changes.

Evaluating the effect of arachidonic acid and eicosapentaenoic acid on induction of adipogenesis in human adipose-derived stem cells.

OBJECTIVES: Adipose tissue is one of the most important endocrine organs that liberates many metabolic mediators such as hormones, cytokines, and chemokines. Different types of fatty acids have key roles in adipogenesis. The aim of this study was to evaluate the effects of two essential fatty acids, including Arachidonic acid (AA) and Eicosapentaenoic acid (EPA), on the process of adipogenicity in human Adipose-Derived Stem Cells (hADSCs). MATERIALS AND METHODS: After immunophenotyping of hADSCs by flowcytometry, they were differentiated into adipocytes and simultaneously exposed to 30 µM and 60 µM of AA and 25 µM and 50 µM of EPA. Further, along with the MTS assay, the activity of glycalaldehyde-3-phosphate dehydrogenase (GAPDH) was also measured. In addition, expression of lipid markers including peroxisome proliferator-activated receptor γ2 (PPARγ2) and glucose transporter 4 (GLUT4) was evaluated, and the neutral lipid contents were determined using Oil red O staining. RESULTS: MTS evaluation showed a significant decrease in proliferation in all treatment groups compared to the control group. Based on oil red O staining, fat droplets in the AA treatment groups were higher than in controls. The expression of PPARγ2 and GLUT4 genes and proteins increased in almost all AA and EPA groups compared to control. In addition, GAPDH activity was higher in AA groups than in the control group. In general, while different concentrations of EPA did not increase the adipogenic process compared to the control group, stimulation of differentiation to adipocytes was largely determined by the AA. CONCLUSION: The result indicates a positive effect of omega-6 versus omega-3 in stimulating the pathways of adipogenesis.

Evaluation of Salivary Lipid Peroxidation End Product Level in Dental Caries.

BACKGROUND: Tissue destruction can be measured by the level of lipid peroxidation (LP) end products. Since free radicals are very reactive with low survival time, the level of free radicals and oxidative stress activity are measured indirectly by tissue damage end product assessment, i.e. Malondialdehyde (MDA) that is a final end product of LP. OBJECTIVE: The aim of this study was to evaluate salivary MDA level as an indicator of oxidative stress; in caries-active and caries-free students. METHODS: A total of 100 male and female students, 15-17 years of age, participated in this casecontrol study. Five mL of whole saliva was obtained. Salivary MDA level was measured spectrophotometrically. Statistical comparisons were performed with Student's t-test, using SPSS 13. RESULTS: Salivary MDA level was significantly higher in the caries-active group compared to the control caries-free group. MDA was also slightly lower in males. CONCLUSION: Higher MDA level might indicate caries-induced oxidative stress. In this study there was a relationship between salivary MDA level and dental caries. Therefore oxidative stress suppression might prevent caries initiation and progression.