The role of ultra-processed food consumption in protein-energy wasting and sarcopenia development in patients with chronic kidney diseases.

BACKGROUND: The effect of ultra-processed foods (UPFs) on chronic kidney disease (CKD) has been studied in some studies. The present study aimed to investigate the association between UPF consumption and the risk of protein-energy wasting (PEW) and sarcopenia in patients with CKD in the Iranian population. METHODS: The current cross-sectional study included 110 patients with CKD referred to two clinics in Shiraz, Iran. The International Society of Renal Nutrition and Metabolism (ISRNM) criteria and the Asian Working Group for Sarcopenia (AWGS) guideline were considered for the diagnosis of PEW and sarcopenia, respectively. The valid semi-quantitative food frequency questionnaire was used to assess participants' dietary intake. The logistic regression was used to examine the association of UPFs with PEW and sarcopenia. RESULTS: We observed no significant association between sarcopenia and PEW with UPFs in the crude model. After adjusting for confounders, we observed a significantly higher odds of sarcopenia in the upper versus lower median of UPF intake (odds ratio (OR) = 3.59, 95% confidence interval (CI): 1.02-12.62, P = 0.046). CONCLUSIONS: Our findings suggest a positive relationship between UPF intake and sarcopenia among CKD patients. Therefore, reducing the intake of UPFs may decrease the odds of sarcopenia in patients suffering from CKD.

Relationship between long non-coding RNAs and Hippo signaling pathway in gastrointestinal cancers; molecular mechanisms and clinical significance.

Long non-coding RNAs (lncRNAs) play a significant biological role in the regulation of various cellular processes such as cell proliferation, differentiation, apoptosis and migration. In various malignancies, lncRNAs interplay with some main cancer-associated signaling pathways, including the Hippo signaling pathway to regulate the various cellular processes. It has been revealed that the cross-talking between lncRNAs and Hippo signaling pathway involves in gastrointestinal (GI) cancers development and progression. Considering the clinical significance of these lncRNAs, they have also been introduced as potential biomarkers in diagnostic, prognostic and therapeutic strategies in GI cancers. Herein, we review the mechanisms of lncRNA-mediated regulation of Hippo signaling pathway and focus on the corresponding molecular mechanisms and clinical significance of these non-coding RNAs in GI cancers.

The association between empirical dietary inflammatory pattern and colorectal cancer risk: a case-control study.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in Iran. Inflammation plays an essential role in developing CRC. A dietary pattern called the empirical dietary inflammatory pattern (EDIP) has recently been designed based on the inflammatory potential of the diet. Therefore, the present study aimed to investigate the impact of EDIP on the risk of CRC. METHODS: The current case-control study was conducted on 142 controls and 71 CRC cases in three general hospitals and Hospital Cancer Organization in Tehran, Iran. We calculated EDIP by a semi-quantitative food frequency questionnaire. The association between EDIP and CRC were evaluated by logistic regression. The level of significance was p < 0.05. RESULTS: The results revealed that people who were in the highest tertile of the EDIP had higher odds of CRC (in the adjusted model: odds ratio (OR) = 3.74; 95% confidence interval (CI): 1.38-10.14; P = 0.011). CONCLUSION: The present study demonstrated the potential role of dietary-induced inflammation in developing CRC. In the current study, an increase in the intake of red meat, processed meats, and refined grains was observed in the higher EDIP tertiles compared to the lower tertiles. Consequently, to decrease the risk of CRC, it is recommended to reduce the consumption of these foods.

Dietary quality index and the risk of breast cancer: a case-control study.

BACKGROUND: Diet quality is a significant determinant in the etiology of breast cancer (BrCa), but further studies are required to explore this relationship. Therefore, we tried to assess if diet quality, assessed using the Diet Quality Index-International (DQI-I), was related to BrCa among the Iranian population. METHODS: In the present case-control research, 134 women with a recent diagnosis of BrCa and 267 without BrCa were selected as case and control groups. Individual food intake data from a food frequency questionnaire was used to compute DQI-I. Also, the multivariable logistic regression models were utilized to evaluate the association between DQI-I and BrCa odds . RESULTS: We found a significant association between the last tertile of DQI-I and BrCa odds in the fully adjusted model (odds ratio (OR) = 0.30; 95% confidence interval (CI): 0.15-0.56). The subgroup analysis based on menopausal status also showed a significant decrease in BrCa odds in pre-and post-menopausal women (pre-menopausal: OR = 0.27; 95% CI: 0.10-0.70 - post-menopausal status: OR = 0.35; 95% CI: 0.13-0.92). CONCLUSIONS: Our findings indicated that a higher DQI-I score was related to a lower chance of BrCa. According to our research, a healthy diet pattern is crucial for BrCa prevention.

Effect of curcumin on the expression of NOD2 receptor and pro-inflammatory cytokines in fibroblast-like synoviocytes (FLSs) of rheumatoid arthritis (RA) patients.

BACKGROUND: Previous studies has shown that nucleotide-binding and oligomerization domain-containing protein 2 (NOD2) is expressed in Fibroblast-like synoviocytes (FLSs) of rheumatoid arthritis (RA) patients which is stimulated by muramyl dipeptide (MDP) present in the joint environment and induces inflammation via the NF-κB pathway. Also, other studies have shown that curcumin inhibits proliferation, migration, invasion, and Inflammation and on the other hand increases the apoptosis of RA FLSs. In this study, we aim to evaluate the effect of curcumin, a natural anti-inflammatory micronutrient, on the expression of NOD2 and inflammatory cytokines. METHODS: Synovial membranes were collected from ten patients diagnosed with RA and ten individuals with traumatic injuries scheduled for knee surgery. The FLSs were isolated and treated with 40 µM curcumin alone or in combination with 20.3 µM MDP for 24 h. mRNA was extracted, and real-time PCR was performed to quantitatively measure gene expression levels of NOD2, p65, IL-6, TNF-α, and IL-1ß. RESULTS: The study findings indicate that administering MDP alone can significantly increase the mRNA expression levels of IL-6 and IL-1ß in the trauma group and TNF-α in the RA group. Conversely, administering curcumin alone or in combination whit MDP can significantly reduce mRNA expression levels of P65 and IL-6 in FLSs of both groups. Moreover, in FLSs of RA patients, a single curcumin treatment leads to a significant reduction in NOD2 gene expression. CONCLUSION: This study provides preliminary in vitro evidence of the potential benefits of curcumin as a nutritional supplement for RA patients. Despite the limitations of the study being an investigation of the FLSs of RA patients, the results demonstrate that curcumin has an anti-inflammatory effect on NOD2 and NF-κB genes. These findings suggest that curcumin could be a promising approach to relieve symptoms of RA.

Carbohydrate quality indices and colorectal cancer risk: a case-control study.

BACKGROUND: Colorectal cancer (CRC) is the fourth and third most common cancer in Iran and the world, respectively. Carbohydrates can lead to the proliferation of cancer cells, including CRC. The current study aimed to investigate the association between glycemic load (GL), insulin load (IL), glycemic index (GI), insulin index (II), low-carbohydrate diet score (LCDS), and carbohydrate quality index (CQI) with CRC odds. METHODS: The present case-control study was performed on 71 CRC cases and 142 controls in the Hospital Cancer Organization and three general hospitals in Tehran, Iran. We calculated the dietary GI, GL, IL, II, CQI, and LCDS by a validated food frequency questionnaire. RESULTS: The results indicated that people who were in the highest tertile of the GI had higher odds of CRC compared to the lower tertile (in the adjusted model: odds ratio (OR) = 3.89; 95% confidence interval (CI): 1.71-8.84). On the contrary, people who were in the highest tertile of the CQI and LCDS had significantly lower odds of CRC compared to the lower tertile (in the adjusted model: tertile (T) 2-OR = 0.24; 95% CI: 0.11-0.53 and T3-OR = 0.15; 95% CI: 0.06-0.39 for CQI and T2-OR = 0.33; 95% CI: 0.13-0.79 and T3-OR = 0.28; 95% CI: 0.10-0.82 for LCDS). Also, IL was positively associated with the odds of CRC after adjusting for confounding factors (T2-OR = 2.46; CI: 1.08-5.61 and T3- OR = 2.80; 95% CI: 1.07-7.31). Regarding the GL, only individuals who were in the second tertile had significantly higher odds of CRC compared to the first tertile (OR = 2.42; CI: 1.07-5.47). CONCLUSION: According to the findings, it is recommended to use a diet with high-quality carbohydrates and low GI and GL to minimize the odds of developing CRC. People should also be encouraged to have a balanced carbohydrate intake.

Effect of curcumin on the expression of NOD2 receptor and pro-inflammatory cytokines in fibroblast-like synoviocytes (FLSs) of rheumatoid arthritis (RA) patients

Abstract Background Previous studies has shown that nucleotide-binding and oligomerization domain-containing protein 2 (NOD2) is expressed in Fibroblast-like synoviocytes (FLSs) of rheumatoid arthritis (RA) patients which is stimulated by muramyl dipeptide (MDP) present in the joint environment and induces inflammation via the NF-κB pathway. Also, other studies have shown that curcumin inhibits proliferation, migration, invasion, and Inflammation and on the other hand increases the apoptosis of RA FLSs. In this study, we aim to evaluate the effect of curcumin, a natural antiinflammatory micronutrient, on the expression of NOD2 and inflammatory cytokines. Methods Synovial membranes were collected from ten patients diagnosed with RA and ten individuals with traumatic injuries scheduled for knee surgery. The FLSs were isolated and treated with 40 μM curcumin alone or in combination with 20.3 μM MDP for 24 h. mRNA was extracted, and real-time PCR was performed to quantitatively measure gene expression levels of NOD2, p65, IL-6, TNF-α, and IL-1β. Results The study findings indicate that administering MDP alone can significantly increase the mRNA expression levels of IL-6 and IL-1β in the trauma group and TNF-α in the RA group. Conversely, administering curcumin alone or in combination whit MDP can significantly reduce mRNA expression levels of P65 and IL-6 in FLSs of both groups. Moreover, in FLSs of RA patients, a single curcumin treatment leads to a significant reduction in NOD2 gene expression. Conclusion This study provides preliminary in vitro evidence of the potential benefits of curcumin as a nutritional supplement for RA patients. Despite the limitations of the study being an investigation of the FLSs of RA patients, the results demonstrate that curcumin has an anti-inflammatory effect on NOD2 and NF-κB genes. These findings suggest that curcumin could be a promising approach to relieve symptoms of RA.

The Impact of Vitamin D Supplementation on the IFNγ-IP10 Axis in Women with Hashimoto's Thyroiditis Treated with Levothyroxine: A Double-blind Randomized Placebo-controlled Trial.

Hashimoto's thyroiditis (HT) results from chemoattraction of inflammatory cells toward the thyroid gland by inducing the production of interferon-gamma (IFNγ)-induced protein 10 (IP10) by T helper (Th) 1 cells. Vitamin D may suppress the IFNγ-IP10 axis, but this new function of vitamin D has not yet been investigated in HT patients. In an intervention and control group, patients received 50000 IU cholecalciferol or placebo every week for three months, respectively. The CD4+ T cells of 40 patients were isolated, and the mRNA expression levels of vitamin D receptor (VDR), peroxisome proliferator-activated receptors (PPAR)-α, and PPAR-γ genes were determined by real-time PCR. ELISA method was used to determine serum levels of vitamin D, tumor necrosis factor-alpha (TNF-α), IFN-γ, and IP10. Vitamin D levels in the intervention group were significantly higher than in the placebo group after supplementation. PPAR-α and PPAR-γ gene expression levels did not differ significantly between the two groups. The serum levels of IP10, IFNγ, and TNF-α decreased significantly in the vitamin D group, as well as in the placebo group.  During this study, vitamin D levels significantly increased in the intervention group and inflammatory factors decreased. Based on the similar results obtained in the placebo group, further studies with larger sample sizes and longer intervention times are recommended.

Does GD2 synthase (GD2S) detect cancer stem cells in blood samples of breast carcinomas?

INTRODUCTION: Cancer stem cells (CSCs) are a theorized subset of cells within the tumor that is thought to drive disease recurrence and metastatic spread. The aim of this study is to investigate mRNA and protein levels of ganglioside GD2 synthase (GD2S), in breast cancer (BC) patients. METHODS: 65 PBMCs of preoperative BC patients without chemotherapy were compared to PBMCs after chemotherapy and controls. RESULTS: GD2S were significantly higher in BC patients after chemotherapy compared to pre-chemotherapy at both mRNA and protein. GD2S was higher in pre-chemotherapy blood samples compared to control samples. CONCLUSIONS: Higher expression of GD2S in BC samples compared to healthy control indicates the potential utility of GD2S as a marker of malignancy.

Stem Cell Therapy Potency in Personalizing Severe COVID-19 Treatment.

Currently, there are no specific and efficient vaccines or drugs for COVID-19, particularly in severe cases. A wide range of variations in the clinical symptoms of different patients attributed to genomic differences. Therefore, personalized treatments seem to play a critical role in improving these symptoms and even similar conditions. Prompted by the uncertainties in the area of COVID-19 therapies, we reviewed the published papers and concepts to gather and provide useful information to clinicians and researchers interested in personalized medicine and cell-based therapy. One novel aspect of this study focuses on the potential application of personalized medicine in treating severe cases of COVID-19. However, it is theoretical, as any real-world examples of the use of genuinely personalized medicine have not existed yet. Nevertheless, we know that stem cells, especially MSCs, have immune-modulatory effects and can be stored for future personalized medicine applications. This theory has been conjugated with some evidence that we review in the present study. Besides, we discuss the importance of personalized medicine and its possible aspects in COVID-19 treatment, then review the cell-based therapy studies for COVID-19 with a particular focus on stem cell-based therapies as a primary personalized tool medicine. However, the idea of cell-based therapy has not been accepted by several scientific communities due to some concerns of lack of satisfactory clinical studies; still, the MSCs and their clinical outcomes have been revealed the safety and potency of this therapeutic approach in several diseases, especially in the immune-mediated inflammatory diseases and some incurable diseases. Promising outcomes have resulted in that clinical studies are going to continue.

Upregulation of Ganglioside GD2 Synthase (GD2S), as a New Putative Cancer Stem Cell Marker in Breast Carcinomas.

Background: GD2 synthase (GD2S) is the key enzyme required for ganglioside GD2 synthesis. It is commonly expressed in normal tissues and various cancers. Ganglioside GD2 is identified as a breast cancer stem cells (BCSCs) marker that promotes tumorigenesis. As GD2S has been found to be a useful molecular marker in neuroblastoma and retinoblastoma tumors, we suggest that it can be considered as a suitable candidate for the detection of CSCs in breast cancer tissues. Methods: Expression of GD2S was examined in 65 breast tumors compared to adjacent normal tissues, applying quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). The association between GD2S expression level and patients' clinical characteristics was also assessed. Results: Our findings showed that GD2S mRNA expression was significantly higher in breast cancer tissues in comparison to normal adjacent tissue samples (4.92-fold change, p<0.001) in advanced grades (p<0.001) and stages (p<0.001). It was also shown that GD2S protein expression was significantly higher in breast cancer tissues in comparison to normal adjacent tissues (4.86-fold change, p=0.010) in advanced grades (p=0.010), stages (p=0.005) and larger tumor size (p=0.002). Conclusion: The current study showed that increased expression of GD2S in advanced breast cancer potentiates it as a promising tumor marker in these patients.

Contraceptive and molecular function of a novel recombinant vaccine based human leukemia inhibitory factor on Balb/c mice: An experimental in vivo study.

The functional competence of leukemia inhibitory factor (LIF), as immunocontraceptive vaccine in mice, was investigated. Balb/c mice were divided into two groups of vaccinated and controls. The recombinant human LIF (rhLIF) protein and phosphate buffer saline was emulsified with Freund's adjuvant and injected into vaccinated and control groups, respectively. Theinhibition of implantation was evaluated in mice uterine. The concentration of secreted interferon-γ (IFN-γ) and interleukin (IL)-4 were measured in cultured splenocyte of mice stimulated by rhLIF. The expressions of immune responsive gene 1 (IRG-1), cochlin (COCH), amphiregulin(Ar), and heparin-binding EGF-like growth factor (HB-EGF) genes were determined. Mice were assessed for inhibition of fertility after delivery, reversibility of immune response against rhLIF, and survival rate. Active immunization of mice with rhLIF resulted in reduction of the implantation and fertility rate up to 80.49% and 75%, respectively. All mice produced a high titer of anti-rhLIF antibodies in serums and vaginal fluids washes after 16 weeks; however, these antibodies were cleared from vaginal fluid washes after six months. A significant down-regulation in mRNA levels of IRG-1, Ar and HB-EGF was observed in vaccinated group compared to controls; however, no significant change in the expression profile of cochlin gene was detected. The results showed that rhLIF prevented pregnancy in a high percentage of female mice. Although the immunization of female Balb/c mice with rhLIF inhibited fertility and expression of genes associated with this molecule, further studies are needed to support this protein as a suitable candidate for contraceptive vaccine in mammals.

Production and characterization of recombinant human leukemia inhibitory factor and evaluation of anti-fertility effects of rabbit anti-rhLIF in Balb/c mice.

Human leukemia inhibitory factor (hLIF) is a cytokine of interleukin-6 family. This study aimed to evaluate the recombinant production rate of active hLIF by different vector-host systems under various conditions. Moreover, a rabbit polyclonal antibody (pAb) against recombinant hLIF (rhLIF) was produced and its anti-fertility effects were explored in Balb/c mice. Four different constructs including pET22b/hLIF, pET28b/hLIF, pET32b/hLIF and pColdI/hLIF were designed and transformed into BL21-(DE3), Rosetta-(DE3), Origami-(DE3) and Shuffle T7-(DE3) host cells. The expression level and proliferative effect of rhLIF were measured by SDS-PAGE and MTT assays, respectively. Rabbit pAb to rhLIF was produced and characterized using enzyme-linked immunosorbent assay and western blot techniques. The Balb/c mice were divided into two intervention and control groups. Then, they were intraperitoneally injected by purified rabbit anti-rhLIF and non-immunized rabbit pAb, respectively. After sacrifice on day 7, the number of implantation sites was counted. The rhLIF was successfully expressed by pET32b/hLIF and pColdI/hLIF vectors in all hosts with no significant difference in the rate of their expression. The rhLIF was purified and checked for activity. The results showed that it is functionally active and the produced anti-rhLIF pAb could specifically bind to commercial rhLIF. Passive immunization results showed that anti-rhLIF antibody completely inhibited fertility in all injected Balb/c mice compared to controls. Although previous studies showed expression of rhLIF using various methods, using different vector-host systems ensures us of successful biological active expression of it. The pAb against rhLIF could be a powerful tool for inducing in vivo infertility.

Molecular miR-19a in Acute Myocardial Infarction: Novel Potential Indicators of Prognosis and Early Diagnosis.

OBJECTIVE: Due to the increasing annual incidence rate of disability and mortality in patients with acute myocardial infarction (AMI), the need for an appropriate diagnostic tool has become a crucial urgent issue. An increase in biomarkers and protein levels in response to AMI can be used as a predictive biomarker with different sensitivities and specificities. This study aimed at investigating the role of miR-19a as a biomarker with acceptable sensitivity and specificity for early diagnosis of AMI. METHODS: We studied 175 patients with AMI admitted within 12 h of symptom onset and 90 healthy subjects as control group. Patients were divided into two groups, including group I (normal vessels and no significant artery stenosis) and primary percutaneous coronary intervention (PCI) group II (patients with more than 50% stenosis in vessels and severe atherosclerosis) diagnosed by angiography. The expression level of miR-19a was evaluated by the real-time polymerase chain reaction and other serum chemistries were also analyzed. RESULTS: The results demonstrated that circulating miR-19a levels were significantly increased in patient groups compared to the control group (2.88 ± 1.06 vs. 5.93 ± 1.28, P<0.0001). We also found that miR-19a levels were higher in group II (134.62-fold) than group I (15.42-fold). The upper levels of miR-19a were significantly correlated with the increased serum levels of CK-MB (ρ=0.29, P<0.0001), CTn I (ρ=0.4, P<0.0001) and creatinine (ρ=0.27, P<0.0001). In addition, Receiver Operating Characteristic (ROC) analysis revealed that circulating miR-19a had considerable diagnostic accuracy for the patients with normal vessel with an AUC of 0.930 (95% CI: 0.697-0.765) and for PCI patients with an AUC of 0.966 (95% CI: 0.748-0.784). CONCLUSION: Circulating miR-19a possibly has prognostic value to be used as a promising molecular target for early diagnosis and prognosis of AMI.

Expression analysis of MiR-21, MiR-205, and MiR-342 in breast cancer in Iran.

MicroRNAs (miRNAs) are short non-coding RNA molecules characterized by their regulatory roles in cancer and gene expression. We analyzed the expression of miR-21, miR-205, and miR-342 in 59 patients with breast cancer. Samples were divided into three different groups according to their immunohistochemistry (IHC) classification: ER-positive and/or PR-positive group (ER+ and/or PR+; group I); HER2-positive group (HER2+; group II); and ER/PR/HER2- negative (ER-/PR-/HER2-; group III) as the triple negative group. The expression levels of the 3 miRNAs were analyzed in the tumor samples and the compared with the normal neighboring dissected tumor (NNDT) samples in all three groups. The expression of miR-21 was similar in all three groups. In patients positive for P53 by IHC, positive for axillary lymph node metastasis and higher tumor stages, it appeared to have significantly elevated. However, significant increase was not found among the 18 fibroadenoma samples. Both miR-205 and miR-342 expressions were significantly down regulated in group III. We conclude that miR-21 does not discriminate between different breast cancer groups. In contrast, miR-205 and miR-342 may be used as potential biomarkers for diagnosis of triple negative breast cancer.

Identification of novel p53 target genes by cDNA AFLP in glioblastoma cells.

The p53 plays critical role in cellular functions such as cell cycle arrest and apoptosis. We overexpressed wild-type p53 (wt-p53) in U87 glioblastoma cells via recombinant adenovirus Ad-GFP-P53 which encodes p53 and green fluorescent protein. The transcript profiles were investigated using cDNA amplified fragment length polymorphism approach. Semi-quantitative RT-PCR and DNA sequencing results for the selected genes showed that Cathepsin B and cell cycle associated protein-1 or Caprin-I, genes were suppressed whereas Annexin-II gene overexpressed in response to the overexpression of wt-p53 gene. Our results suggest that these genes could be important mediators of p53-dependent tumor growth suppression in glioblastoma.