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Glioblastoma multiforme (GBM) is a common, aggressive, fast-growing tumor of the central nervous system that currently has no effective treatment. Although stem cell therapy has shown promising in vitro achievements, the blood-brain barrier (BBB) has always been a major hurdle to clinical success. To overcome this challenge, exosomes have been targeted as attractive drug delivery agents in numerous studies since they are small enough to enter the BBB. Furthermore, exosomes' characteristics and compositions are directly determined by the parent cell and these heritable traits affect their cell interactions. This article focuses on exosomes as an alternative to stem cell therapy to regulate glioma cell activity. Exosomes were isolated from rat bone marrow mesenchymal stem cells (rBMMSCs) by ultracentrifugation method and then characterized via western blot, dynamic light scattering, scanning, and transmission electron microscopy. Next, various concentrations of the exosomes were incubated with C6 cells and their effects at different time points were evaluated in vitro. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Annexin/Pi assay results confirmed that the isolated exosomes cause cell death mostly through apoptosis, and a linear correlation was observed between exosomes' concentration and their cytotoxicity. Following that, the scratch test, colony formation test, and Transwell assay confirmed exosomes' significant impact on the migration and invasion behavior of C6 cells. For the first time, rBMMSC-derived exosomes have been used as a single treatment for GBM rather than in combination with other treatments or as a pharmaceutical carrier., (© 2022 International Federation for Cell Biology.)

In neuronal network analysis on, for example, synchronization, it has been observed that the influence of interactions between pairwise nodes is essential. This paper further reveals that there exist higher-order interactions among multi-node simplicial complexes. Using a neuronal network of Rulkov maps, the impact of such higher-order interactions on network synchronization is simulated and analyzed. The results show that multi-node interactions can considerably enhance the Rulkov network synchronization, better than pairwise interactions, for involving more and more neurons in the network.

Background: Studies have shown that the CDK5R1 gene could have a part in some types of cancer. This study sought to examine the relationship between CDK5R1 expression and prognosis and medication resistance in 13 commonly occurring cancers., Method: The cancer genome atlas data and clinical data were utilized to assess the role of CDK5R1 in malignancies. The expression data of 13 cancers were also integrated and used for the co-expression network. The relationship between CDK5R1 expression and drug resistance and sensitivity was evaluated using pharmacogenomics data. The colorectal cancer (CRC) and breast cancer (BC) were used to confirm the results through the RT-qPCR method., Results: With the exception of gastric cancer, all common malignancies showed an increase in CDK5R1 expression. Also, outcomes of sensitivity and specificity showed that CDK5R1 level could be a really good potential biomarker. Additionally, CDK5R1 expression was higher in CRC and BC samples compared to adjacent normal, according to RT-qPCR data. In six types of tumors and combined data, a poor prognosis was associated with increased CDK5R1 expression. The CDK5R1-associated genes were connected to the primary oncogenic pathways in cancer cells, according to the co-expression network. Also, CDK5R1 level was significantly linked to the resistance and sensitivity of several chemotherapy drugs and caused the highest resistance to cyclophosphamide., Conclusion: CDK5R1 expression is upregulated in 12 prevalent cancers and can play an oncogenic role. Also, this gene's expression could be used as a biomarker to predict patient survival and medication resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This meta-analysis aimed to investigate the association of the rs9939609 FTO gene polymorphism and body fat percentage (BF%). To the best of our knowledge, this study is the first meta-analysis to evaluate the relationship between FTO rs9939609 polymorphism and BF%. We searched PubMed, Web of science, Scopus and Embase to identify studies investigating the relations between the rs9939609 FTO gene polymorphism and BF%. Studies that meet inclusion criteria were collected for the final analysis. There was significant differences in the level of BF% between different genotypes of FTO rs9939609 polymorphism, and the carriers of the A allele of FTO rs9939609 polymorphism had higher BF%. The association was significant between carriers of TT genotype compared to carriers of AA ( p  = .007) and AT genotypes ( p  = .04), but not between AT and AA genotypes. This study identified that the carriers of the A allele of FTO rs9939609 polymorphism have higher BF%.

Urological cancers include bladder, prostate and renal cancers that can cause death in males and females. Patients with urological cancers are mainly diagnosed at an advanced disease stage when they also develop resistance to therapy or poor response. The use of natural products in the treatment of urological cancers has shown a significant increase. Curcumin has been widely used in cancer treatment due to its ability to trigger cell death and suppress metastasis. The beneficial effects of curcumin in the treatment of urological cancers is the focus of current review. Curcumin can induce apoptosis in the three types of urological cancers limiting their proliferative potential. Furthermore, curcumin can suppress invasion of urological cancers through EMT inhibition. Notably, curcumin decreases the expression of MMPs, therefore interfering with urological cancer metastasis. When used in combination with chemotherapy agents, curcumin displays synergistic effects in suppressing cancer progression. It can also be used as a chemosensitizer. Based on pre-clinical studies, curcumin administration is beneficial in the treatment of urological cancers and future clinical applications might be considered upon solving problems related to the poor bioavailability of the compound. To improve the bioavailability of curcumin and increase its therapeutic index in urological cancer suppression, nanostructures have been developed to favor targeted delivery., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Medication errors are among the most common life-threatening mistakes made in health care. The ability to accurately calculate drug doses, especially in intensive care units (ICUs), where the majority of medications are infused, reduces medication errors. Researchers have proposed dimensional analysis to improve mathematical calculations of drugs. This study was conducted to determine the effects of dimensional analysis on the infusible medication calculation skills among nursing students in ICUs. In this quasi-experimental study, the research samples consisted of sixth-semester nursing students who were assigned to an intervention group (n = 34) and a control group (n = 32). For the intervention group, the calculations of common infusible drugs in the ICU were taught using the dimensional analysis method, whereas the control group received training without the dimensional analysis method. Data collection instruments included a demographic characteristics questionnaire and a 10-item questionnaire of drug calculations that were measured before and after the intervention in both groups. Data analysis was performed using SPSS 22. The mean pretest scores for infusible drug calculations of nursing students in the ICU were 5.15 ± 2.35 for the intervention group and 5.25 ± 2.56 for the control group (P = .86). The mean posttest scores of the intervention group and control group were 9.22 ± 0.79 and 6.27 ± 1.87, respectively (P = .0001). Dimensional analysis training significantly improved the infusible medication calculation skills of nursing students in the ICU. It is recommended to include this method in undergraduate, graduate, and continuing education nursing courses to increase skills in calculating infusible drugs and to reduce medication errors., Competing Interests: Disclosures: The authors of this article have no conflicts of interest to disclose., (Copyright © 2022 Infusion Nurses Society.)

Objectives: The association between major dietary patterns and metabolic health status in adolescents has been understudied, especially in Middle Eastern populations. The aim of this study was to evaluate this association in overweight/obese adolescents., Methods: In this cross-sectional study, the usual of 203 overweight/obese adolescents selected by a multistage, cluster random-sampling method was evaluated through a validated food frequency questionnaire. Anthropometric indices and blood pressure values were measured. Fasting blood samples were obtained to determine insulin, glucose, and lipid profile concentrations. Two methods (modified International Diabetes Federation [IDF] criteria and IDF criteria along with insulin resistance or homeostasis model assessment insulin resistance [HOMA-IR] >3.16) were applied to classify participants into metabolically healthy obese (MHO) or unhealthy obese (MUO)., Results: Two major dietary patterns, Mediterranean-like and Western, were identified. After adjustments for potential confounders, high adherence to Mediterranean-like dietary pattern was related to 72% (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.10-0.76) and 67% (OR, 0.33; 95% CI, 0.11-0.98) lower odds for being MUO based on IDF and HOMA-IR definitions, respectively. Higher adherence to the Western dietary pattern was related to higher odds of being MUO, either in the crude or adjusted models in both metabolic status definitions (for IDF definition: OR, 9.85; 95% CI, 2.75-35.19; for HOMA-IR definition: OR, 9.15; 95% CI, 2.02-41.52, in fully adjusted model)., Conclusions: We found an inverse association between the Mediterranean-like dietary pattern and odds of MUO in Iranian overweight/obese adolescents, whereas the Western dietary pattern was associated with an increased likelihood of being MUO. Further studies, with a prospective nature, are required to confirm these findings., Competing Interests: Conflict of interest None, (Copyright © 2022. Published by Elsevier Inc.)

We report on a 47-year-old patient suffering from bilateral gonalgia, weight loss and night sweats without fever of several months' duration. Diagnostic work-up for infectious and autoimmune diseases showed no abnormal results. A CT scan showed extensive foci of sclerosis throughout the axial skeleton. In the trephine biopsy, foamy cell infiltrates were found with expression of histiocytic markers without expression of Langerhans cell markers. Molecular analysis revealed a low allelic BRAF V600E and BCOR mutation. The diagnosis of Erdheim-Chester disease (ECD) was made. The histologic findings and molecular findings, the clinical and radiologic presentation before and 6 months after therapy as well as possible differential diagnoses of this very rare disease are discussed., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

There was a lack of evidence on the association between dairy intake and metabolic health status in overweight/obese adolescents. This study evaluated the association between dairy intake and metabolic health status in overweight/obese Iranian adolescents. Overweight/obese adolescents (n = 203; 101 boys and 102 girls) selected by a multistage cluster random sampling method have participated in this cross-sectional study. Dietary intake was assessed using a validated 147-item food frequency questionnaire. Anthropometric indices, blood pressure, fasting glucose, insulin, and lipid profile were measured. Participants were categorized to metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) according to International Diabetes Federation (IDF) criteria and a combination of IDF with Homeostasis Model Assessment Insulin Resistance (HOMA-IR) criteria. The frequency of MUO based on IDF, and IDF/HOMA-IR definitions was 38.9% and 33.0%, respectively. In fully-adjusted model, participants in the highest tertile of dairy intake had 61% lower odds of MUO based on IDF criteria (OR = 0.39, 95% CI 0.15-0.99). Higher dairy intake was associated with a non-significant lower risk of MUO according to IDF/HOMA-IR definition in the maximally-adjusted model (OR = 0.44, 95% CI 0.17-1.16). Stratifies analysis by sex and body mass index revealed that the association was stronger in girls and overweight subjects. Furthermore, higher intake of low-fat dairy was related to a reduced likelihood of MUO, while higher intake of high-fat dairy was related to increased odds of MUO. This community-based cross-sectional study revealed that higher intake of dairy was associated with a significant lower odd of MUO among Iranian adolescents, especially in girls and overweight subjects., (© 2022. The Author(s).)

Long noncoding RNAs (lncRNAs) as regulatory molecules play important roles in early treatment and diagnosis of cancers. Considering the role of PPARγ in colorectal cancer (CRC) as a tumor suppressor, the GEO database was used to identify candidate genes that affect the activation of PPARγ protein in CRC cell lines. Then were selected 5 genes containing PPARγ response element (PPRE) in up to 4000 bp upstream and were affected by PPARγ protein activation in HT-29 colon cancer cell line using UCSC database. Expression meta-analysis was applied to map the expression network between candidate genes and all known lncRNAs through expression correlation and lncRNAs that correlated with a greater number of candidate genes (R > 0.5, P.value < 0.001). Moreover, were selected 3 lncRNAs as lncRNAs affected by PPARγ protein activation. Next, the expression levels of candidate genes and lncRNAs were evaluated using RT-qPCR in HT-29 cell line. Results showed a significant increase (FDR <0.05) in the expression level of 5 candidate genes and lncRNAs LINC01133, MBNL1-AS, LOC100288911 after treatment with pioglitazone as PPARγ ligand compared to the untreated group in HT-29 cells. Although additional tests are needed to confirm bioinformatics predictions, it can be concluded that increased expression of PPARγ may increase genes and lncRNAs expression. In summary, this study could be suggested identifying lncRNAs affected by PPARγ activation could be a new strategy in understanding the function and activity of PPARγ in colon cancer., Competing Interests: Declaration of competing interest All of the authors have declared that no competing interests exist., (Copyright © 2022. Published by Elsevier B.V.)

The use of land-based ecological potential is a key management factor in achieving sustainable development and conserving soil and water resources. The purpose of this study is to use multi-time images of Sentinel-2 to determine the area of agricultural lands and evaluate their ecological potential in Bastam, Semnan Province, Iran. Therefore, in the first step, the most common agricultural lands (including apricot and grape orchards), field crops (including wheat and forage maize), and their phenological period were determined. Then, the information was classified using, namely support vector machine, maximum likelihood, and minimum distance. In the next step, soil, topography, and climate data were extracted according to expert opinions and the analysis of the basin's natural potential. The ecological evaluation models of the region were applied to homogeneous units, and after calculating the ecological potential index by the integrated ANP-WLC model, the ecological potential map was generated. The results of the land use classification showed that the support vector machine model and the minimum distance, respectively, had the best and worst performance with kappa coefficient of 0.82 and 0.61. The highest area of cultivated lands (3423 hectares) was estimated for wheat and the lowest (738 hectares) for forage maize. Moreover, the results of the ecological potential evaluation showed that 60% of apricot orchards, and 40.19% of the wheat fields, were in the class of good ecological potential. Overall, 2290 hectares were in the poor class, and 4030 hectares in the excellent class in terms of ecological potential., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

RNA molecules lacking capacity in protein translation, are known as non-coding RNAs (ncRNAs). Growth, differentiation and migration are influenced by ncRNAs in cells. The abnormal expression of ncRNAs contributes to development of diseases, especially cancer. On the other hand, EMT is a vital mechanism for cancer invasion and diffusion in body. In this manuscript, role of ncRNAs in EMT regulation and subsequent effect on cancer progression is investigated. The miRNAs regulate EMT by affecting signaling pathways including PI3K/Akt and PTEN to modulate cancer metastasis. Furthermore, miRNA and EMT interaction has close association with drug sensitivity of tumor cells. LncRNAs can affect EMT via targeting ZEB1/2, Twist and Snail among others and similarly, based on the impact on EMT, sensitivity of cancer cells to therapy increases or decreases. CircRNAs regulate both drug sensitivity and metastasis of cancers by affecting EMT mechanism. Noteworthy, circRNAs and lncRNAs are capable of sponging miRNAs in modulating EMT mechanism. Exosomes belong to extracellular vesicles with low size that can be secreted by cells in transferring genetic materials. The transfer of ncRNAs by exosomes is performed and they can also regulate EMT in cancer progression. Finally, ncRNAs regulating EMT mechanism are used for cancer diagnosis and prognosis., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Limited evidence is available regarding the association of methyl donor nutrients and adolescents' metabolic health. Therefore, we investigated the relation between a combination of methyl donor nutrients and metabolic health status of overweight and obese Iranian adolescents. In this cross-sectional study, 203 overweight/obese adolescents were included, using a multistage cluster random-sampling method. Dietary intakes were assessed by a validated food frequency questionnaire. Methyl donor nutrient score (MDNS) was constructed based on deciles of vitamins B2, B6, B9, B12, methionine, choline and betaine. Glycemic profile, lipid profile, blood pressure and anthropometric indices were collected. Participants were classified as metabolically healthy obese or unhealthy obese (MUO) based on International Diabetes Federation (IDF) and IDF/Homeostasis Model Assessment Insulin Resistance (HOMA-IR) definitions. Mean age of adolescents was 13.98 [Formula: see text] 1.61 y and 50.2% of them was girls. After controlling all of the confounders, individuals in the top tertile of MDNS, had lower odds of MUO (OR 0.36; 95% CI 0.13-0.95) according to IFD criteria. Considering IDF/HOMA-IR criteria, an inverse marginally significant association was observed between the highest tertile of MDNS and odds of MUO (OR 0.36; 95% CI 0.12-1.02) in the fully-adjusted model. Furthermore, significant inverse association was found between each unit increase in MDNS and odds of MUO based on IDF criteria, but not for IDF/HOMA-IR definition. We found that overweight/obese adolescents with higher dietary intakes of methyl donor nutrients were less likely to be metabolically unhealthy. Further studies are needed to confirm the findings., (© 2022. The Author(s).)

Template-assisted synthesis of well-defined polynuclear clusters remains a challenge for [M 4 ] square planar topologies. Herein, we present a tetraamine scaffold R L(NH 2 ) 4 , where L is a rigidified resorcin[4]arene, to direct the formation of C 4 -symmetric R L(NH) 4 Cu 4 clusters with Cu-Cu distances around 2.7 Å, suggesting metal-metal direct interactions are operative since the sum of copper's van der Waals radii is 2.8 Å. DFT calculations display HOMO to HOMO-3 residing all within a 0.1 eV gap. These four orbitals display significant electron density contribution from the Cu centers suggesting a delocalized electronic structure. The one-electron oxidized [Cu 4 ] + species was probed by variable temperature X-band continuous wave-electron paramagnetic resonance (CW-EPR), which displays a multiline spectrum at room temperature. This work presents a novel synthetic strategy for [M 4 ] clusters and a new platform to investigate activation of small molecules., (© 2022 Wiley-VCH GmbH.)

Breast cancer (BC) is one of the most common cancers in females and is responsible for the highest cancer-related deaths following lung cancer. The complex tumor microenvironment and the aggressive behavior, heterogenous nature, high proliferation rate, and ability to resist treatment are the most well-known features of BC. Accordingly, it is critical to find an effective therapeutic agent to overcome these deleterious features of BC. Resveratrol (RES) is a polyphenol and can be found in common foods, such as pistachios, peanuts, bilberries, blueberries, and grapes. It has been used as a therapeutic agent for various diseases, such as diabetes, cardiovascular diseases, inflammation, and cancer. The anticancer mechanisms of RES in regard to breast cancer include the inhibition of cell proliferation, and reduction of cell viability, invasion, and metastasis. In addition, the synergistic effects of RES in combination with other chemotherapeutic agents, such as docetaxel, paclitaxel, cisplatin, and/or doxorubicin may contribute to enhancing the anticancer properties of RES on BC cells. Although, it demonstrates promising therapeutic features, the low water solubility of RES limits its use, suggesting the use of delivery systems to improve its bioavailability. Several types of nano drug delivery systems have therefore been introduced as good candidates for RES delivery. Due to RES's promising potential as a chemopreventive and chemotherapeutic agent for BC, this review aims to explore the anticancer mechanisms of RES using the most up to date research and addresses the effects of using nanomaterials as delivery systems to improve the anticancer properties of RES., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Initiation and development of cancer depend on multiple factors that mutations in genes and epigenetic level can be considered as important drivers. Epigenetic factors include a large family of members and understanding their function in cancer has been a hot topic. LncRNAs are RNA molecules with no capacity in synthesis of proteins, and they have regulatory functions in cells. LncRNAs are localized in nucleus and cytoplasm, and their abnormal expression is related to development of tumor. This manuscript emphasizes on the role of lncRNA H19 in various cancers and its association with tumor hallmarks. The function of lncRNA H19 in most tumors is oncogenic and therefore, tumor cells increase its expression for promoting their progression. LncRNA H19 contributes to enhancing growth and cell cycle of cancers and by EMT induction, it is able to elevate metastasis rate. Silencing H19 induces apoptotic cell death and disrupts progression of tumors. LncRNA H19 triggers chemo- and radio-resistance in cancer cells. miRNAs are dually upregulated/down-regulated by lncRNA H19 in increasing tumor progression. Anti-cancer agents reduce lncRNA H19 in impairing tumor progression and increasing therapy sensitivity. A number of downstream targets and molecular pathways for lncRNA H19 have been detected in cancers including miRNAs, RUNX1, STAT3, β-catenin, Akt2 and FOXM1. Clinical studies have revealed potential of lncRNA H19 as biomarker and its association with poor prognosis. LncRNA H19 can be transferred to cancer cells via exosomes in enhancing their progression., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Epigenetic factors are critical regulators of biological and pathological mechanisms and they could interact with different molecular pathways. Targeting epigenetic factors has been an idea approach in disease therapy, especially cancer. Accumulating evidence has highlighted function of long non-coding RNAs (lncRNAs) as epigenetic factors in cancer initiation and development and has focused on their association with downstream targets. microRNAs (miRNAs) are the most well-known targets of lncRNAs and present review focuses on lncRNA-miRNA axis in malignancy and therapy resistance of tumors. LncRNA-miRNA regulates cell death mechanisms such as apoptosis and autophagy in cancers. This axis affects tumor metastasis via regulating EMT and MMPs. Besides, lncRNA-miRNA axis determines sensitivity of tumor cells to chemotherapy, radiotherapy and immunotherapy. Based on the studies, lncRNAs can be affected by drugs and genetic tools in cancer therapy and this may affect expression level of miRNAs as their downstream targets, leading to cancer suppression/progression. LncRNAs have both tumor-promoting and tumor-suppressor functions in cancer and this unique function of lncRNAs has complicated their implication in tumor therapy. LncRNA-miRNA axis can also affect other signaling networks in cancer such as PI3K/Akt, STAT3, Wnt/β-catenin and EZH2 among others. Notably, lncRNA/miRNA axis can be considered as a signature for diagnosis and prognosis in cancers., Competing Interests: Competing interests The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Masson SAS.)

Development of a computational technique for the analysis of quasi-normal modes in hybrid-plasmonic resonators is the main goal of this research. Because of the significant computational costs of this analysis, one has to take various symmetries of these resonators into account. In this research, we consider cylindrical symmetry of hybrid-plasmonic ring resonators and implement a body-of-revolution finite-difference time-domain (BOR-FDTD) technique to analyze these resonators. We extend the BOR-FDTD method by proposing two different sets of auxiliary fields to implement multi-term Drude-Lorentz and multi-term Lorentz models in BOR-FDTD. Moreover, we utilize the filter-diagonalization method to accurately compute the complex resonant frequencies of the resonators. This approach improves numerical accuracy and computational time compared to the Fourier transform method used in previous BOR-FDTD methods. Our numerical analysis is verified by a 2D axisymmetric solver in COMSOL Multiphysics.

The anti-angiogenic effects of harmaline, an alkaloid with emerging anti-tumor properties, are under investigation. In the present study, the effects of different doses of harmaline, either alone or in combination with doxorubicin (DOX), were assessed in mice models of breast tumor. Breast tumors were created by the subcutaneous injection of 4T1 cells into Balb/c mice. The mice received either normal saline, harmaline alone (10, 20, or 30 mg/kg), or harmaline (20 mg/kg) + DOX (10 mg/kg). Immunohistochemistry, ELISA, and real-time PCR were conducted to measure target parameters. Harmaline significantly increased tumor cells' sensitivity to DOX as confirmed by a significantly reduced tumor volume in the harmaline + DOX group after 24 days (P < 0.05). Also, the levels of Ki-67 (P < 0.001), MMP-2 (P < 0.001), and VEGF (P < 0.001) significantly decreased while the level of E-cadherin increased (P < 0.001) in the tumor tissues of the mice treated with 20 or 30 mg/kg harmaline or harmaline (20 mg/kg) + DOX (10 mg/kg) compared to the control group. There was a significant reduction in the serum level of IL-4 in tumor-bearing mice treated with harmaline (P < 0.05), and IFN-γ serum level was significantly augmented in all experimental groups compared to the control group (P < 0.05). The genes encoding VEGF, VEGF receptor 2, CD105, and COX2 were significantly down-regulated (P < 0.05 for all) in harmaline-treated (either alone or in combination with DOX) mice. In conclusion, harmaline seems to have the potential to be used as an anticancer agent for treating breast cancer., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mohsen Rashidi reports financial support was provided by Mazandaran University of Medical Sciences. Mohsen Rashidi reports a relationship with Mazandaran University of Medical Sciences that includes: funding grants. The authors declare that there is no conflict of interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Green chemistry has been a growing multidisciplinary field in recent years showing great promise in biomedical applications, especially for cancer therapy. Chitosan (CS) is an abundant biopolymer derived from chitin and is present in insects and fungi. This polysaccharide has favorable characteristics, including biocompatibility, biodegradability, and ease of modification by enzymes and chemicals. CS-based nanoparticles (CS-NPs) have shown potential in the treatment of cancer and other diseases, affording targeted delivery and overcoming drug resistance. The current review emphasizes on the application of CS-NPs for the delivery of a chemotherapeutic agent, doxorubicin (DOX), in cancer therapy as they promote internalization of DOX in cancer cells and prevent the activity of P-glycoprotein (P-gp) to reverse drug resistance. These nanoarchitectures can provide co-delivery of DOX with antitumor agents such as curcumin and cisplatin to induce synergistic cancer therapy. Furthermore, co-loading of DOX with siRNA, shRNA, and miRNA can suppress tumor progression and provide chemosensitivity. Various nanostructures, including lipid-, carbon-, polymeric- and metal-based nanoparticles, are modifiable with CS for DOX delivery, while functionalization of CS-NPs with ligands such as hyaluronic acid promotes selectivity toward tumor cells and prevents DOX resistance. The CS-NPs demonstrate high encapsulation efficiency and due to protonation of amine groups of CS, pH-sensitive release of DOX can occur. Furthermore, redox- and light-responsive CS-NPs have been prepared for DOX delivery in cancer treatment. Leveraging these characteristics and in view of the biocompatibility of CS-NPs, we expect to soon see significant progress towards clinical translation., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

Purpose: Tumor necrosis factor alpha (TNF-α) is an inflammatory cytokine which may play a role in the development of gastric cancer (GC). This study aimed to investigate the association of five TNF-α polymorphisms including TNF-α-857, TNF-α-1031, TNF-α-863, TNF-α-308, and TNF-α-238 polymorphisms with GC risk., Methods: All eligible case-control studies were collected by searching PubMed, Scopus, and Web of Science. The association of the risk of GC with TNF-α polymorphisms was estimated using odds ratio (OR) and 95% confidence interval (CI). Heterogeneity was assessed via Cochrane's Q and I 2 analyses., Results: A total of 46 publications involving 16, 715 cases with GC and 27, 998 controls were recruited. The study revealed a significant association for TNF-α 308 (recessive model: OR = 0.646, P = 0.035), TNF-α-1031 (homozygote model: OR = 1.584, P = 0.027), and TNF-α-857 (homozygote model: OR = 1.760, P = 0.001) polymorphisms with the GC risk. The results of subgroup analysis based ethnicity found a significant association between GC risk and TNF-α-857 polymorphism in Caucasian subgroup (P = 0.005) and TNF-α-1031 polymorphism and GC risk in Asians (P = 0.018)., Conclusions: This study suggested that TNF-α-857 and TNF-α-1031 polymorphisms may be associated with the increased gastric cancer risk., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Crocin, an active ingredient derived from saffron, is one of the herbal components that has recently been considered by researchers. Crocin has been shown to have many anti-inflammatory and antioxidant properties, and therefore can be used to treat various diseases. It has been shown that Crocin has a positive effect on the prevention and treatment of cardiovascular disease, cancer, diabetes, and kidney disease. In addition, the role of this substance in COVID-19 pandemic has been identified. In this review article, we tried to have a comprehensive review of the antioxidant and anti-inflammatory effects of Crocin in different diseases and different tissues. In conclusion, Crocin may be helpful in pathological conditions that are associated with inflammation and oxidative stress., Competing Interests: Conflict of interest statement All authors declare that there is no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

In January 2019, a 30-year-old woman admitted to our inpatient department presented with undulating fever, pain in several joints, and significantly elevated liver enzymes and lactate dehydrogenase. After extended examination, infection with Brucella melitensis with liver, musculoskeletal, and pulmonary involvement was diagnosed and treated. Diagnosis was based on clinical examination, laboratory findings including seroconversion as a proof of immune response, magnetic resonance imaging, three-phase bone scintigraphy, and F‑18 FDG-PET (F-18 Flourdeoxyglucose positron emission tomography) illustrating the bone involvement and its normalization upon treatment. After treatment the patient showed a remarkable improvement of clinical symptoms within a short period. The patient remained symptom free and polymerase chain reaction (PCR) testing for brucellosis was negative, even at the follow-up examination 12 months after the end of the antibiotic therapy. The family members were also examined due to the similar travel history, and by this, brucellosis was also diagnosed in her husband but not in her children., (© 2021. Springer-Verlag GmbH Austria, ein Teil von Springer Nature.)

Background: Implantation of vascular access devices is of great importance in critically ill patients or those vulnerable to clinical worsening. The aim of this study was to identify the complications of implantation of vascular access leading to complaints from patients, in the forensic medicine commissions of Tehran., Methods: The present descriptive-cross sectional study was performed on all cases that died from implantation of vascular access devices and complaints about permanent local complications caused by this procedure, filed with the forensic medicine commissions of Tehran in period of 2013-2018, based on selected variables, and the results were statistically analyzed using the chi-square and Fisher exact tests in SPSS Version 18. A p-value of <0.01 was considered statistically significant., Results: All alleged deaths were due to implantation of central venous port placed in a large vein in the neck, and most organ failure cases were attributed to anterior forearm deformity. The most common cause of death was acute cardiac death; internal bleeding was observed in 14% of them. Most complaints of death were filed against general surgery and anesthesia assistants, and most complaints about peripheral venipuncture were against trainee nurses. The present study findings were significantly different in terms of cannulation site, age, cause of death, type of local complication (p<0.01)., Conclusion: This study shows, as patients become more aware, complaints from physicians about implantation of vascular access, in the judicial authority are also on the rise. Therefore, in choosing these patients, Venice should be treated more carefully., Competing Interests: The authors declared no potential conflict of interest with respect to the authorship and/or publication of this article.

Obesity is one of the risk factors concerns of colorectal cancer (CRC), the most common type of gastrointestinal cancer, due to the changing lifestyle and especially diet. There are various molecular pathways associated with obesity and the risk of CRC incidence, such as insulin resistance or elevated plasma free fatty acids, which alter the signaling pathways of intestinal epithelial cells. The aim of this study was to better understand the significance of unsaturated fatty acid biosynthesis on pathogenesis of colon cancer in obese. Based on GSE20931 dataset, obese individuals affected by CRC had higher increased gene expression than non-obese individuals. The analysis showed that in obese individuals, the 16 signaling pathway genes were activated and increased (FDR <0.05) significantly. The biosynthetic pathway of unsaturated fatty acids showed a cross-talk with the arachidonic acid metabolism pathway and the PPAR signaling pathway is influenced and regulated via these pathways. The biosynthetic pathway of unsaturated fatty acids consisting of 22 genes, were analyzed using GEO data and revealed that 4 genes (HSD17B12, TECR, FADS2, ELOVL5) from this pathway were significantly increased (FDR <0.05). These data were validated based on TCGA data (Adj.p.value <0.001). The expression level of candidate genes in HT-29 cells decreased significantly (P.value <0.01), and PPARγ expression increased under linoleic acid treatment (200 μM) compared to control cells. Moreover, in presence of linoleic acid treatment, migration, colony formation, and proliferation decreased (P.value <0.01) in presence of treatment. In summary, the Biosynthesis pathway of unsaturated fatty acids is an interesting and critical pathway in CRC., Competing Interests: Conflict of interest All of the authors have declared that no competing interests exist., (Copyright © 2022. Published by Elsevier Masson SAS.)

Background: Although several studies evaluated the relationship between individual dietary antioxidants and metabolic health conditions, data on the association between dietary total antioxidant capacity and metabolic health among children and adolescents is limited. This study investigated the relationship between dietary total antioxidant capacity and metabolic health status in Iranian overweight/obese adolescents., Methods: This cross-sectional study was conducted on 203 overweight/obese adolescents. Dietary intakes were evaluated by a validated food frequency questionnaire. Ferric Reducing-Antioxidant Power (FRAP) was considered to indicate dietary total antioxidant capacity. Anthropometric parameters and blood pressure status were measured. Fasting blood samples were obtained to determine circulating insulin, glucose, and lipid profile. Two different methods (modified International Diabetes Federation (IDF) criteria and IDF criteria along with insulin resistance) were applied to classify participants as metabolically healthy obese (MHO) or metabolically unhealthy obese (MUO)., Results: According to IDF and IDF/HOMA definitions, a total of 79 (38.9%) and 67 (33.0%) adolescents were respectively defined as MUO. Considering IDF criteria, the highest tertile of FRAP was related to lower odds of being MUO in the maximally-adjusted model (OR: 0.40; 95%CI: 0.16-0.96), compared to the lowest tertile. However, based on the IDF/HOMA-IR criteria, no significant relation was found between FRAP and odds of MUO (OR: 0.49; 95%CI: 0.19-1.23) after considering all possible confounders., Conclusions: Adolescents with higher intakes of dietary antioxidants have a lower possibility of being MUO based on IDF criteria. However, no substantial relation was found considering HOMA-IR/IDF definition. Further prospective cohort studies need to be done to confirm these findings., (© 2022. The Author(s).)

Radiomics (RC) was initially developed using computed tomography (CT) for oncological imaging. However, it can be applied to various scientific and clinical radiology fields regardless of the modalities involved. The purpose of this survey was to evaluate alterations in magnetic resonance imaging of the heart (CMR) in patients suffering from autoimmune thyroid disorders (AITD) by applying RC tools and mapping features. A total of 50 individuals were evaluated in this study. We searched for CMR examinations performed in our department between January 2019 and 2021 in patients with AITD. Thirty patients with AITD (21 men and 9 women, aged 51 to 78 years; mean age, 60 years) were enrolled in our survey. We enrolled a control group (CG) of 20 individuals (14 men and 6 women aged 53-87 years; mean age, 68 years) without AITD or cardiac disorders. Global native T1 and T2 mapping revealed no significant differences between groups. However, we identified significantly higher values of several texture parameters, including the gray-level co-occurrence matrix (GLCM) entropy, gray-level run-length matrix (GLRLM; short-run high gray-level emphasis (SRHGE), GLCM (Energy), gray-level size zone matrix length matrix (GLZLM; LZLGE), GLZLM (SZLGE), DISCRETIZED (HISTO-Energy) GLCM (Dissimilarity), and GLCM (Contrast), in patients with AITD in comparison to the CG (P < .01). Our results indicate that several RC properties extracted from CMR images can be used to discriminate between the AITD and CG groups., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Coatings are now frequently used on cutting tool inserts in the metal production sector due to their better wear resistance and heat barrier effect. Protective hard coatings with a thickness of a few micrometers are created on cutting tools using physical or chemical vapor deposition (PVD, CVD) to increase their application performance. Different coating materials are utilized for a wide range of cutting applications, generally in bi-or multilayer stacks, and typically belong to the material classes of nitrides, carbides, carbonitrides, borides, boronitrides, or oxides. The current study examines typical hard coatings deposited by PVD and CVD in the corresponding material classes. The present state of research is reviewed, and pioneering work on this subject as well as recent results leading to the construction of complete "synthesis-structure-property-application performance" correlations of the different coatings are examined. When compared to uncoated tools, tool coatings prevent direct contact between the workpiece and the tool substrate, altering cutting temperature and machining performance. The purpose of this paper is to examine the effect of cutting-zone temperatures on multilayer coating characteristics during the metal-cutting process. Simplified summary and comparisons of various coating types on cutting tools based on distinct deposition procedures. Furthermore, existing and prospective issues for the hard coating community are discussed., Competing Interests: The authors declare no conflict of interest.

Background: Although the relationship between TP53 mutation, TP53 metabolism pathways, and tumorigenesis has been investigated, pan-cancer analysis of TP53 mutations and related metabolism pathways is not completely available in common types of human cancers. Thus, this study was going to represent TP53 mutant-related metabolism genes and pathways in a pan-cancer study and investigate the relationship between selected genes and drug resistance., Methods: The DNA-seq data, RNA-seq data, and clinical information of 12 types of cancer were downloaded from the cancer genome atlas (TCGA) database. GSE70479 data were obtained from GEO database for validation of our TCGA data. To evaluate the survival rate of patients, GEPIA2 was applied. The CCLE and GDSC database were used to investigate drug resistance and sensitivity., Results: Our findings indicated that TTN, MUC16, and TP53 were present in 12 types of cancer with high level of mutation frequency which abundance of TP53 mutations was higher. Mutant TP53-related (mTP53) pathways and genes including PKM, SLC16A3, HK2, PFKP, PHGDH, and CTSC were obtained from enrichment analysis and interestingly, top pathways were associated with metabolism including glycolysis and mTORC1 pathway. Our results showed the expression of some candidate genes correlated with immune markers, prognosis, and drug resistance., Conclusions: Top mutant genes for 12 cancers were highlighted while TP53 was selected as top mutant gene, and metabolic genes associated with the TP53 mutation were identified that some of which are important in poor prognosis. In doing so, mutations in TP53 could run some metabolic pathways and drug resistance and sensitivity., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The association of plant-based diets with health status is underestimated in pediatrics. We aimed to examine the relation between plant-based diets (including overall plant-based index (PDI), healthy plant-based (hPDI) and unhealthy plant-based (uPDI)) and metabolic health status in Iranian adolescents with overweight/obesity. We conducted a cross-sectional study on 203 adolescents with overweight/obesity (12-18 years old) selected by a multistage cluster random-sampling method. Usual dietary intakes were assessed through a validated 147-item food frequency questionnaire (FFQ). Anthropometric indices and blood pressure values were measured and fasting blood samples were drawn. For classification of participants into metabolically healthy obese (MHO) or metabolically unhealthy obese (MUO) groups, two methods of International Diabetes Federation (IDF) and combination of IDF with Homeostasis Model Assessment Insulin Resistance (HOMA-IR) were applied. No significant association was observed between higher adherence to PDI and odds of MUO status defined by both IDF and IDF/HOMA-IR strategies. After adjustments for all potential confounders, adolescents in the highest tertile of hPDI, compared with those in the lowest tertile, had 85% (95% CI 0.05-0.43) and 84% (95% CI 0.05, 0.52) lower odds of being MUO based on IDF and IDF/HOMA-IR criteria, respectively. Greater adherence to uPDI was associated with odd of 3.95 (95% CI 1.41, 11.12) and 4.06 (95% CI 1.31, 12.57) of being MUO based on IDF and IDF/HOMA-IR definitions, after considering all potential confounders. Stratified analysis revealed that these associations were stronger in girls and overweight subjects. Adherence to healthy plant-based foods was inversely associated with odds of MUO status in Iranian adolescents. In contrast, unhealthy plant-based diets was directly associated with MUO in pediatrics. Further studies with prospective nature, are required to affirm these results., (© 2022. The Author(s).)

Background: Obesity is becoming more prevalent around the world and greatly contributes to chronic disease progression. Previous studies have investigated individual food groups in relation to metabolic health status of adolescents, mainly in Western countries. Limited data are available on the association between dietary patterns and metabolic health in Middle East nations, where childhood overweight/obesity is increasing drastically. Therefore, we investigated the relationship between the Mediterranean diet and metabolic health status among Iranian adolescents., Methods: This cross-sectional study was conducted on 203 overweight/obese adolescents. Dietary intakes were evaluated by a validated food frequency questionnaire. Anthropometric parameters and blood pressure were measured. Fasting blood samples were obtained to determine circulating insulin, glucose, and lipid profile. Two different methods were applied to classify participants as metabolically healthy obese (MHO) or unhealthy obese (MUO): International Diabetes Federation (IDF) criteria and IDF along with insulin resistance (HOMA-IR) criteria., Results: A total of 79 (38.9%) and 67 (33.0%) adolescents were, respectively, categorized as MUO, based on IDF and IDF/HOMA definitions. Considering IDF criteria, higher adherence to the Mediterranean diet was related to lower odds of being MUO, both in the crude (OR: 0.17; 95%CI: 0.08-0.37) and fully adjusted model (OR: 0.33; 95% CI: 0.13-0.84). Excluding each component from the score made the association insignificant, except for two components of meat and dairy products. Based on the IDF/HOMA-IR criteria, there was no significant association between Mediterranean diet score and MUO, after considering all potential confounders (OR: 0.47; 95% CI: 0.17-1.30)., Conclusions: We found an inverse association between the Mediterranean diet and odds of MUO among Iranian adolescents, based on IDF criteria. No significant relation was found when MUO was defined based on HOMA-IR/IDF criteria. Further prospective cohort studies are needed to confirm these findings., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Sobhan Mohammadi et al.)

We employed density functional theory (DFT) methods to investigate the most plausible mechanism of cyclization/ring expansion of proline with o -alkynylbenzaldehyde. This one-pot reaction starts with the in situ formation of azomethine ylide, which can undergo three different reaction pathways to form the final product. Two mechanisms are based on nucleophilic addition and 4π-electrocyclization of the azomethine ylide, and our results indicate that the rate-determining step (RDS) of these two cyclizations are 40.1 and 40.2 kcal/mol, respectively. The third novel pathway relies upon 8π-electrocyclization as the key step of this reaction; interestingly, the RDS of this cyclization is ∼20.6 kcal/mol, which shows this route to be most feasible. Thus, we introduce a novel mechanism for the electrocyclization reaction of conjugated azomethine ylides that can help chemists to design and access a new series of compounds.

Patients with chronic diseases are severely affected by acute coronavirus syndrome. In this regard, patients with beta thalassemia intermedia and diabetes mellitus (DM ) are also at high risk for coronavirus-induced respiratory failure. The present study aimed to report a case with COVID-19 with a history of chronic diseases, beta thalassemia intermedia, and DM. A 25-year-old man visited with complaints of severe shortness of breath, fever, cough without sputum, and tachypnea and admitted to the Intensive Care Unit. The patient had a history of DM, beta thalassemia intermedia, and pervious history of the splenectomy. In peripheral complete blood count (CBC diff), the number of white blood cell count was 41,100 of which 38.6% were lymphocytes. We measured the normal platelet count, hemoglobin level (9.4), and red blood cell count (3.56). ESR was 97, CRP = pos+++ and PCR was positive. The high-resolution lung CT indicated ground glass opacities in peripheral areas. The patient underwent 13 days of oxygen therapy with reservoir bag-mask, non-invasive ventilation, nasal oxygen, and pharmacological treatment with IFN-β1a and meropenem, and finally discharged with an improvement of the clinical condition. Timely initiation of treatment is very important and significant for patients with beta thalassemia intermedia with COVID-19, especially despite the underlying disease of DM. According to the present report, the use of IFN-β1a was effective as a treatment option for COVID-19., Competing Interests: The authors declare that they have no competing interests., (© 2022 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Despite progress in diagnosis and treatment of esophageal cancer (EC), it is still considered as a serious malignancy with very poor prognosis. Urolithins are colonic microbiota metabolites with a wide range of pharmacological properties including chemopreventive, anti-inflammatory and anticancer activities. In this study, we hypothesized that urolithins might possess the potential to improve the efficacy of chemical drugs, ionizing radiation (IR) and/or hyperthermia on EC cells. After synthesis of urolithin A (UA), methylurolithin A (mUA) and urolithin B (UB), KYSE30 esophageal cancer cells were treated with urolithins + paclitaxel (PTX), + cisplatin (DDP), + different doses of IR or + heat-shock. Viability of cells was then determined by alamarBlue assay. To further elucidate the effects of UA, we used flow cytometry for investigation of induced apoptosis, and qRT-PCR for evaluating changes in the expression of HSP27, CCND1 and BCL2. Assessment of cell viability demonstrated that mUA increased the toxicity of PTX and DDP (up to 22.4 % and 20 %, respectively) and improved the effects of 6 Gy IR (26.5 %). Our main results achieved after UA treatment were improved toxicity of PTX and 6 Gy IR, beside enhanced effects of hyperthermia (37.3 %), which was confirmed by flow cytometry analysis and downregulation of HSP27, CCND1 and BCL2 expression. Taken together, our findings suggest that UA and mUA could be used as promising agents in combination with therapeutic modalities to improve the clinical outcomes of EC treatment., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: To assess dose levels in routine nuclear medicine (NUC) procedures in Austria as a prior to a legislative update of the National Diagnostic Reference Levels (NDRL)., Method: As part of a nationwide survey of common NUC-examinations between June 2019 and November 2019, data sets were collected from 33 Austrian hospitals with NUC equipment. All hospitals were asked to report the NUC imaging devices in use (model, type, year of manufacture, detector material, collimators), the standard protocol parameters for selected examinations (standard activity, collimator, average acquisition time, reconstruction type, use of time-of-flight) and to report data from 10 representative examinations (e.g. injected activity, weight), incl. the most common NUC-examinations for planar imaging/SPECT and PET. Median/mean values for injected activity were calculated and compared to current Austrian and international NDRL. A Pearson correlation coefficient was computed comparing different variables., Results: In total, all 33 hospitals (100% response rate) reported data for this study for 60 SPECT devices, 21 PET/CT devices and 23 scintigraphy devices. Fixed activity values for scintigraphy/SPECT and PET were employed by about 90% and 56% of the hospitals, respectively. The most widely performed examinations for scintigraphy/SPECT are bone imaging, thyroid imaging, renal imaging (with MAG3/EC) and lung perfusion imaging (in 88% of the hospitals) and F-18 FDG-PET studies for oncology indications (in 100% of the hospitals). Significant correlations were found for patient weight and injected activity (scintigraphy/SPECT), use of iterative reconstruction and injected activity (PET) as well as size of field-of-view and injected activity (PET)., Conclusions: The reported injected activity levels were comparable to those in other countries. However, for procedures for which NDRL exist, deviations in injected activities of >20% compared to the NDRL were found. These deviations are assumed to result mainly from advances in technology but also from deviations between NDRL and prescribed activities as given in the information leaflets of the radiopharmaceuticals., (Copyright © 2021. Published by Elsevier GmbH.)

Utilizing a plasma focus (PF) instrument, magnesium nitride (Mg 3 N 2 ) thin films were synthesized on stainless steel substrates. Twenty five optimum focus shots at 8 cm distance from the anode tip were used to deposit the films at different angular positions regarded to the anode axis. Scanning electron microscopy (SEM), atomic force microscopy (AFM), and X-ray diffraction (XRD) analyses were performed to assess the surface morphology and structural characteristics of Mg 3 N 2 films. Based on AFM images, these films were studied to understand the effect of angular position variation on their surfaces through morphological and fractal parameters. By increasing the angle, we verify that the grain size decreased from 130(0) nm to 75(5) nm and also the mean quadratic surface roughness of the films reduced in its average values from (28.97 ± 3.24) nm to (23.10 ± 1.34) nm. Power spectrum density analysis indicated that films become more self-affine at larger angles. Furthermore, the corrosion behavior of the films was investigated through a potentiodynamic polarization test in H 2 SO 4 solution. It was found that the ion energy and flux, varying with the angular positions from the anode tip, directly affected the nanostructured roughness and surface morphology of the samples. The electrochemical studies of films show that the uncoated sample presented the lowest corrosion resistance. The highest corrosion resistance was obtained for the sample deposited with 25 optimum shots and at 0° angular position reaching a reduction in the corrosion current density of almost 800 times compared to the pure stainless steel-304 substrate. HIGHLIGHTS: Mg 3 N 2 /SS films have been deposited at different angles by plasma focus (PF) instruments. The effect of angular position on the surface microtexture, morphological parameters, and corrosion features of the films was studied. The RBS measurement and X-ray diffraction are utilized to identify the crystalline phases and thickness of films., (© 2022 Wiley Periodicals LLC.)

Objective: Genetics and dietary factors play important roles in the development of colorectal cancer (CRC). However, the underlying mechanisms of the interactions between CRC, gene polymorphisms, and dietary fat are unclear. This review study investigated the effects of polymorphisms of arachidonate lipoxygenase ( ALOX ) and cyclooxygenase ( COX ) genes in the association between CRC and dietary fat., Methods: All the related papers published from 2000 to 2022 were collected from different databases such as PubMed, Science Direct, Scopus, and Cochran using related keywords such as colorectal cancer, ALOX , COX , polymorphism, and dietary fat. Non-English and unrelated documents were excluded., Results: Some single-nucleotide polymorphisms ( SNPs ) in the ALOX and COX genes, such as rs2228065, rs6413416, and rs4986832 in the ALOX gene, and rs689465 in the COX gene may play significant roles in the association between the risk of CRC and dietary fats. SNPs of ALOX and COX genes may influence the effects of dietary fatty acids on the risk of CRC., Conclusion: Some polymorphisms of the ALOX and COX genes may have important roles in the effects of dietary fat on the risk of CRC. If future studies confirm these results, dietary recommendations for preventing colorectal cancer may be personalized based on the genotype of the ALOX and COX genes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gholamalizadeh, Majidi, Tajaddod, Abdollahi, Poorhosseini, Ahmadzadeh, Naimi Joubani, Mirzaei Dahka, Shafaei, Hajiesmaeil, Alizadeh, Doaei and Houshiar-Rad.)

This is a randomized controlled trial conducted in a tertiary referral fertility department. Participants were women with previous poor ovarian response undergoing in vitro fertilization. (IVF). One hundred and ninety-two women were randomized to the short GnRH agonist and antagonist regimens. The primary outcome was the number of oocytes retrieved. Secondary outcome measures were the number of embryos transferred, chemical and clinical pregnancy rate and live birth. The number of oocytes retrieved was higher with the gonadotrophin-releasing hormone (GnRH) antagonist regimen compared to the short agonist regimen (3.10 2.70 vs. 2.992.60), but there was no significant difference. The duration of stimulation and total gonadotropin dose were higher with short agonist regimens compared to antagonist regimens, with the latter being statistically significant (p < 0.001). The chemical pregnancy rate was 8.33 percent with the short agonist regimen and 7.29 percent with the antagonist regimen, with no statistically significant difference (p = 0.79). In terms of lower cycles cancelation and higher chemical pregnancy, short GnRH agonist regim is appropriate choice for poor responders.

Background: One of the most malignant tumors in men is prostate cancer that is still incurable due to its heterogenous and progressive natures. Genetic and epigenetic changes play significant roles in its development. The RNA molecules with more than 200 nucleotides in length are known as lncRNAs and these epigenetic factors do not encode protein. They regulate gene expression at transcriptional, post-transcriptional and epigenetic levels. LncRNAs play vital biological functions in cells and in pathological events, hence their expression undergoes dysregulation., Aim of Review: The role of epigenetic alterations in prostate cancer development are emphasized here. Therefore, lncRNAs were chosen for this purpose and their expression level and interaction with other signaling networks in prostate cancer progression were examined., Key Scientific Concepts of Review: The aberrant expression of lncRNAs in prostate cancer has been well-documented and progression rate of tumor cells are regulated via affecting STAT3, NF-κB, Wnt, PI3K/Akt and PTEN, among other molecular pathways. Furthermore, lncRNAs regulate radio-resistance and chemo-resistance features of prostate tumor cells. Overexpression of tumor-promoting lncRNAs such as HOXD-AS1 and CCAT1 can result in drug resistance. Besides, lncRNAs can induce immune evasion of prostate cancer via upregulating PD-1. Pharmacological compounds such as quercetin and curcumin have been applied for targeting lncRNAs. Furthermore, siRNA tool can reduce expression of lncRNAs thereby suppressing prostate cancer progression. Prognosis and diagnosis of prostate tumor at clinical course can be evaluated by lncRNAs. The expression level of exosomal lncRNAs such as lncRNA-p21 can be investigated in serum of prostate cancer patients as a reliable biomarker., (© 2022. The Author(s).)

The nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of redox balance and it responds to various cell stresses that oxidative stress is the most well-known one. The Nrf2 should undergo nuclear translocation to exert its protective impacts and decrease ROS production. On the other hand, ischemic/reperfusion (I/R) injury is a pathological event resulting from low blood flow to an organ and followed by reperfusion. The I/R induces cell injury and organ dysfunction. The present review focuses on Nrf2 function in alleviation of I/R injury. Stimulating of Nrf2 signaling ameliorates I/R injury in various organs including lung, liver, brain, testis and heart. The Nrf2 enhances activity of antioxidant enzymes to reduce ROS production and prevent oxidative stress-mediated cell death. Besides, Nrf2 reduces inflammation via decreasing levels of pro-inflammatory factors including IL-6, IL-1β and TNF-α. Nrf2 signaling is beneficial in preventing apoptosis and increasing cell viability. Nrf2 induces autophagy to prevent apoptosis during I/R injury. Furthermore, it can interact with other molecular pathways including PI3K/Akt, NF-κB, miRNAs, lncRNAs and GSK-3β among others, to ameliorate I/R injury. The therapeutic agents, most of them are phytochemicals such as resveratrol, berberine and curcumin, induce Nrf2 signaling in I/R injury alleviation., (Copyright © 2022. Published by Elsevier Inc.)

Metastasis of tumor cells is a complex challenge and significantly diminishes the overall survival and prognosis of cancer patients. The epithelial-to-mesenchymal transition (EMT) is a well-known mechanism responsible for the invasiveness of tumor cells. A number of molecular pathways can regulate the EMT mechanism in cancer cells and nuclear factor-kappaB (NF-κB) is one of them. The nuclear translocation of NF-κB p65 can induce the transcription of several genes involved in EMT induction. The present review describes NF-κB and EMT interaction in cancer cells and their association in cancer progression. Due to the oncogenic role NF-κB signaling, its activation enhances metastasis of tumor cells via EMT induction. This has been confirmed in various cancers including brain, breast, lung and gastric cancers, among others. The ZEB1/2, transforming growth factor-β, and Slug as inducers of EMT undergo upregulation by NF-κB to promote metastasis of tumor cells. After EMT induction driven by NF-κB, a significant decrease occurs in E-cadherin levels, while N-cadherin and vimentin levels undergo an increase. The noncoding RNAs can potentially also function as upstream mediators and modulate NF-κB/EMT axis in cancers. Moreover, NF-κB/EMT axis is involved in mediating drug resistance in tumor cells. Thus, suppressing NF-κB/EMT axis can also promote the sensitivity of cancer cells to chemotherapeutic agents., (© 2022 Wiley Periodicals LLC.)

Cancer is one of the leading causes of death worldwide, and the factors responsible for its progression need to be elucidated. Exosomes are structures with an average size of 100 nm that can transport proteins, lipids, and nucleic acids. This review focuses on the role of exosomes in cancer progression and therapy. We discuss how exosomes are able to modulate components of the tumor microenvironment and influence proliferation and migration rates of cancer cells. We also highlight that, depending on their cargo, exosomes can suppress or promote tumor cell progression and can enhance or reduce cancer cell response to radio- and chemo-therapies. In addition, we describe how exosomes can trigger chronic inflammation and lead to immune evasion and tumor progression by focusing on their ability to transfer non-coding RNAs between cells and modulate other molecular signaling pathways such as PTEN and PI3K/Akt in cancer. Subsequently, we discuss the use of exosomes as carriers of anti-tumor agents and genetic tools to control cancer progression. We then discuss the role of tumor-derived exosomes in carcinogenesis. Finally, we devote a section to the study of exosomes as diagnostic and prognostic tools in clinical courses that is important for the treatment of cancer patients. This review provides a comprehensive understanding of the role of exosomes in cancer therapy, focusing on their therapeutic value in cancer progression and remodeling of the tumor microenvironment., (© 2022. The Author(s).)

The relationship between dietary acid load (DAL) and metabolic health status in adolescents has not been studied yet. We aimed to examine the association between DAL and metabolic health status in Iranian overweight/obese adolescents. This cross-sectional study included 203 overweight/obese adolescents selected by a multistage cluster random sampling method. Dietary intakes were assessed using a validated 147-item food frequency questionnaire (FFQ). Anthropometric indices and blood pressure values were measured. Fasting blood samples were obtained to determine glucose, insulin, and lipid profiles. Based on two methods (International Diabetes Federation (IDF) criteria and combination of IDF with Homeostasis Model Assessment Insulin Resistance (HOMA-IR)), participants were classified into metabolically healthy obese (MHO) or unhealthy obese (MUO). Adolescents in the highest tertile of potential renal acid load (PRAL) and net endogenous acid production (NEAP), compared with those in the lowest tertile, had 172% (95% CI 1.32-5.59) and 161% (95% CI 1.26-5.41) higher odds of MUO status, based on IDF criteria. This association was significant after adjustment for age, sex, and energy intake (PRAL: OR 2.42; 95% CI CI 1.13-5.15; NEAP: OR 2.52; 95% CI 1.17-5.41); but it disappeared after adjustment for other confounders. Based on IDF/HOMA-IR definition, there was a significant positive association between PRAL and being MUO only in the crude model (OR 2.37; 95% CI 1.13-4.96). The stratified analysis revealed that these associations for NEAP scores were stronger among overweight subjects than obese individuals, based on both metabolic status definitions. However, after adjustment for all potential confounders these relations were insignificant. Having higher DAL might be associated with higher odds of MUO phenotype in Iranian overweight/obese adolescents. More prospective studies are warranted to confirm this finding., (© 2022. The Author(s).)

Urological cancers are among the most common malignancies around the world. In particular, bladder cancer severely threatens human health due to its aggressive and heterogeneous nature. Various therapeutic modalities have been considered for the treatment of bladder cancer although its prognosis remains unfavorable. It is perceived that treatment of bladder cancer depends on an interdisciplinary approach combining biology and engineering. The nanotechnological approaches have been introduced in the treatment of various cancers, especially bladder cancer. The current review aims to emphasize and highlight possible applications of nanomedicine in eradication of bladder tumor. Nanoparticles can improve efficacy of drugs in bladder cancer therapy through elevating their bioavailability. The potential of genetic tools such as siRNA and miRNA in gene expression regulation can be boosted using nanostructures by facilitating their internalization and accumulation at tumor sites and cells. Nanoparticles can provide photodynamic and photothermal therapy for ROS overgeneration and hyperthermia, respectively, in the suppression of bladder cancer. Furthermore, remodeling of tumor microenvironment and infiltration of immune cells for the purpose of immunotherapy are achieved through cargo-loaded nanocarriers. Nanocarriers are mainly internalized in bladder tumor cells by endocytosis, and proper design of smart nanoparticles such as pH-, redox-, and light-responsive nanocarriers is of importance for targeted tumor therapy. Bladder cancer biomarkers can be detected using nanoparticles for timely diagnosis of patients. Based on their accumulation at the tumor site, they can be employed for tumor imaging. The clinical translation and challenges are also covered in current review., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

Few studies have investigated dietary total protein intake and its subtypes in relation to metabolic health status. We explored the relation between dietary total, plant and animal protein intake with metabolic health status in Iranian overweight/obese adolescents. Overweight/obese adolescents (n = 203) were selected for this cross-sectional study by multistage cluster random-sampling method. A validated food frequency questionnaire was used to evaluate dietary intakes. Total, plant and animal protein intake were considered as percentage of energy intake. Anthropometric indices, blood pressure, lipid and glycemic profiles were collected. Participants were classified as metabolically healthy obese (MHO) or unhealthy obese (MUO) based on International Diabetes Federation (IDF) and IDF/Homeostasis Model Assessment Insulin Resistance (HOMA-IR) definitions. Subjects had a mean age of 13.98 years, and 50.2% of them were girls. Based on IDF criteria, adolescents in the top tertile of total (OR = 0.32; 95% CI 0.13-0.77), plant (OR = 0.30; 95% CI 0.10-0.91), and animal (OR = 0.20; 95% CI 0.08-0.54) protein intake had lower odds of being MUO compared to the reference category. Considering IDF/HOMA-IR criteria, subjects in the highest tertile of total (OR = 0.31; 95% CI 0.12-0.79) and animal (OR = 0.17; 95% CI 0.06-0.49) protein intake were less likely to be MUO. However, no substantial association was observed with plant protein intake. Also, an inverse association was observed between each SD increase in total and animal protein with MUO odds. We found inverse association between total, plant and animal protein intake and chance of being MUO in adolescents. Further prospective studies are needed to confirm the findings., (© 2022. The Author(s).)

This study characterized quinolone (Q) resistance determinants in a series of Klebsiella pneumoniae ( n  = 26) and Escherichia coli ( n  = 19) isolates of human and animal origin. The presence of plasmid-mediated quinolone resistance (PMQR) and carabpenemase genes was examined by PCR. The quinolone resistance-determining regions (QRDRs) of gyrA and parC genes were sequenced. Thirty-three isolates had ciprofloxacin MIC≥8 mg/l. About 34.6% and 10.5% of K. pneumoniae and E. coli isolates were ESBL producers respectively. The PMQR genes were detected in 77% ( n  = 35) of isolates. The oqxAB was the most prevalent PMQR gene being identified in all K. pneumoniae isolates, followed by aac(6')-Ib-cr (34.6%), qnrS (23%) and qnrB (7.7%). The most frequently detected gene among E. coli isolates was qnrS (36.8%) followed by aac(6')-Ib-cr (10.5%) and qepA (5.2%). All Q resistant isolates harbored amino acid substitutions in both GyrA and ParC QRDRs. High prevalence of PMQR genes among food-producing animal isolates is an issue of great concern.

Aims: Test for an association between prehospital delay for symptoms suggestive of acute coronary syndrome (ACS), persistent symptoms, and healthcare utilization (HCU) 30-days and 6-months post hospital discharge., Background: Delayed treatment for ACS increases patient morbidity and mortality. Prehospital delay is the largest factor in delayed treatment for ACS., Methods: Secondary analysis of data collected from a multi-center prospective study. Included were 722 patients presenting to the Emergency Department (ED) with symptoms that triggered a cardiac evaluation. Symptoms and HCU were measured using the 13-item ACS Symptom Checklist and the Froelicher's Health Services Utilization Questionnaire-Revised instrument. Logistic regression models were used to examine hypothesized associations., Results: For patients with ACS (n = 325), longer prehospital delay was associated with fewer MD/NP visits (OR, 0.986) at 30 days. Longer prehospital delay was associated with higher odds of calling 911 for any reason (OR, 1.015), and calling 911 for chest related symptoms (OR, 1.016) 6 months following discharge. For non-ACS patients (n = 397), longer prehospital delay was associated with higher odds of experiencing chest pressure (OR, 1.009) and chest discomfort (OR, 1.008) at 30 days. At 6 months, longer prehospital delay was associated with higher odds of upper back pain (OR, 1.013), palpitations (OR 1.014), indigestion (OR, 1.010), and calls to the MD/NP for chest symptoms (OR, 1.014)., Conclusions: There were few associations between prehospital delay and HCU for patients evaluated for ACS in the ED. Associations between prolonged delay and persistent symptoms may lead to increased HCU for those without ACS., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Ischemia is a pathological process in which blood supply to a particular organ is temporarily interrupted resulting in disturbed biological function and homeostasis of local tissues. Following ischemia, reperfusion and reoxygenation may occur which further worsens oxidative stress-mediated damage in cells and tissues. The combined processes are referred to as ischemia/reperfusion (I/R) injury. Immediate management and treatment of I/R is of utmost importance for preventing irreversible and extensive cellular damage. Apoptosis, inflammation and oxidative stress are the most validated pathologies associated with I/R. AMP-activated protein kinase (AMPK) modulates energy metabolism in cells and its activation occurs in response to elevated AMP and ADP levels. Aberrant levels of AMPK are noted in various pathological settings such as diabetes mellitus, cancer and neurological diseases. This review emphasizes AMPK signaling, its related molecular pathways and therapeutic utility during I/R. Activation of AMPK through phosphorylation prevents apoptosis and reduces oxidative stress and inflammation upon I/R. Inducing AMPK signaling normalizes mitochondrial function to inhibit cell death. Autophagy as a cytoprotective mechanism undergoes activation by AMPK/mTOR and AMPK/ULK1 pathways. AMPK reinforces the antioxidant defense capacity via Nrf2 signaling to counteract oxidative stress in I/R. Protective compounds including phytochemicals activate AMPK to alleviate I/R injury., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The risk of cervical cancer was reported to be influenced by dietary components. This study aimed to illustrate the association between cervical cancer with the intake of food groups in women with a history of cervical neoplasia., Methods: This nested case-control study was conducted in 558 people with a history of cervical intraepithelial neoplasia (CIN), including 279 women with cervical cancers and 279 controls with low-grade squamous intraepithelial lesions (LSIL). A validated food frequency questionnaire (FFQ) was used to assess the intake of food groups., Results: The intake of fruits and vegetables in the case group was significantly lower than the control group (P=0.001). Low intake of dairy products, vegetables, and fruits was associated with cervical cancer risk (OR=4.67; 95% CI 1.2-9.49, P=0.001; OR=9.75, 95% CI 1.36-19. 51, P=0.001; and OR=4.82, 95% CI 1.09-7.25, P=0.001, respectively). After adjusting for age, family history, age at first menstruation, number of children, history of vaginal infection, and age at first sexual intercourse, the results were still significant. Additional adjustments to BMI did not change the results., Conclusion: The results indicate that the risk of cervical cancer can be affected by the intake of certain food groups. Further longitudinal studies are needed to confirm these findings and determine the underlying mechanism of the influence of dietary components on cervical cancer risk., Competing Interests: The authors have no conflicts of interest to declare.