New long noncoding RNA biomarkers and ceRNA networks on miR-616-3p in colorectal cancer: Bioinformatics-based study.

Background: Cancer development is aided by the role of long noncoding RNAs (lncRNAs) that act as competing endogenous RNAs (ceRNAs) absorbing microRNAs (miRNAs). We aimed to discover a novel regulatory axis in colorectal cancer (CRC) and potential biomarkers based on miR-616-3p. Materials and Methods: The gene expression omnibus database was mined for differentially expressed lncRNAs (DELs) and mRNAs. LncRNAs and mRNAs were predicted using the RegRNA and TargetScan databases. A combination of the ciBioPortal and Ensemble databases was used to locate the mRNAs. Cytoscape 3.7.1-built CeRNA networks. A quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to confirm the expression levels of these RNA molecules. Statistical analyses were implemented by GraphPad Prism 9. Results: qRT-PCR showed (Linc01282, lnc-MYADM-1:1, and Zinc Finger Protein 347 [ZNF347]) were overexpressed whereas, (salt-inducible kinases 1 [SIK1], and miR-616-3p) were down regulated. Conclusion: These results identify unique, unreported lncRNAs as CRC prognostic biomarkers, as well as prospective mRNAs as new treatment targets and predictive biomarkers for CRC. In addition, our study uncovered unexplored ceRNA networks that should be studied further in CRC.

Trend of the polyp and adenoma detection rate by sex and age in asymptomatic average-risk and high-risk individuals undergoing screening colonoscopy, 2012-2019.

Adenoma detection rate (ADR) is an imperative quality measure for colorectal cancer (CRC) screening. This retrospective observational study aimed to determine the trend of polyp detection rate (PDR) and ADR in asymptomatic average- and high-risk participants in different age groups who underwent screening colonoscopy over the seven years from April 2012 to March 2019 in a tertiary gastroenterology referral center of Iran. Of 1676 participants, 51.8 % were men (mean age 52.3 years). The overall PDR and ADR were 22.7 %, and 13.5 %, respectively. Both Polyps and adenomas were more common in age groups 51-59 and ≥60 years in high-risk patients than in the corresponding groups of average-risk patients (p < 0.05). Also, both PDR and ADR were more frequent in men than in women among all studied age groups, but it was statistically significant only for the youngest age group (16.8 % versus 10.5 %, p < 0.05) for PDR and the oldest age group (19.7 % versus 13 %, p < 0.05) for ADR, respectively. The trend of total ADR was upward over 7 years in both average-risk (6.7 % to 13.3 %) and high-risk (9.8 % to 27 %) groups and across all age groups in both sexes. Multivariable logistic regression revealed that high-risk individuals had an elevated risk of adenoma compared with average-risk patients (OR: 1.6, p = 0.006). Substantial variation in thresholds of polyp and adenoma detection by age, sex, and risk categories emphasizes the need for a risk-adapted approach to CRC screening and prevention programs.

A Review of Heavy Metals Accumulation in Red Meat and Meat Products in the Middle East.

The problem of food contamination is a matter of concern, which cancausehealthcomplications in consumers.Severalinternational organizations have created standard permissible limits for heavy metals in meat products. Livestock such as sheep, cattle, camels, and goats are the most important sources of protein meat in the Middle East (ME) countries. Contamination of meat products with heavy metals (HMs) may be a threat to human health. Various scattered studies have been conducted in the Middle East on the contamination of red meat and meat products with HMs however, a comprehensive review on this subject has not yet been published. This study aimed to investigate the status of HMs in both raw andprocessedtypes of meatin the ME. Theresultsof thisnarrativereviewrevealed that in many ME countries, contamination of red meat with HMs was excessive. Therefore, more monitoringoflivestockconditionsandred meat products consumed in some Middle East countries seems necessary.

Rescue effect of curcumin against copper toxicity.

Turmeric has long been used not only as an indispensable part of Asian cuisine but as a medicinal herb for dressing wounds, bites, burns, treating eye infections and acne. Curcuminoids are the active substances and their synthetic derivatives (i.e. diacetylcurcumin (DAC) and metal-curcumin complexes) possess an incredibly wide range of medicinal properties that encompass chelation capacity for multiple heavy metals, antioxidant activity, anti-inflammatory properties, cytotoxicity against cancerous cells, antiviral and antibacterial effects, antihypertensive and insulin sensitizing role, and regulatory role on apoptosis. The aforementioned properties have put curcumin on spotlight as a potential treatment for ailments such as, hepatic diseases, neurodegenerative diseases, metabolic syndrome, dyslipidemia, cardiovascular disease, auto-immune diseases, malignancies and conditions associated with metal overload. Copper is essential for major biological functions, however, an excess causes chronic ailments including neurodegenerative disorders. The fascinating approach of curcumin could alleviate such effect by forming a complex. Thus, this review aims to present available data on the effect of copper-curcumin interaction in various in vitro, ex-vivo in vivo, and clinical studies.

Constructing a novel competing Endogenous RNAs network based on NR3C1 and X-linked inhibitor of apoptosis protein genes reveals potential prognostic biomarkers in colorectal cancer.

Background: Long noncoding RNAs (lncRNAs) have been recognized as the main modulatory molecules in various cancers and perform as competing endogenous RNAs (ceRNAs). The nuclear hormone receptor superfamily of ligand-activated transcription factors (NR3C1) regulates numerous proliferative and metabolic processes such as tumorigenesis and metabolic diseases. Furthermore, X-linked inhibitor of apoptosis protein (XIAP) belongs to a family of the inhibitors of apoptosis proteins, is located downstream of the glucocorticoid receptor (GR or NR3C1) pathway, and cooperates with GR to suppress apoptosis. However, the underlying mechanisms of NR3C1 and XIAP in colorectal cancer (CRC) remain mainly unclear. This research aims to clarify the potential RNA biomarkers and to construct a novel ceRNA network in CRC. Materials and Methods: Multistep bioinformatics methods such as Lnc2cancer and miRDB databases were applied to identify candidate lncRNAs and miRNAs. The interaction energy between lncRNAs, NR3C1, and XIAP genes was analyzed by the LncRRIsearch database. Plus, microRNAs and lncRNA were evaluated via the Diana tools database to select microRNAs with the most binding scores. Quantitative reverse transcription-polymerase chain reaction (QRT-PCR) was applied to verify RNA molecules' expression levels and their association with the clinicopathological factors in 30 CRC tissues compared to 30 adjacent tissues. Results: QRT-PCR showed upregulation of KCNQ1OT1, NR3C1, and XIAP and downregulation of miR-421. The ceRNA network was constructed with 17 lncRNAs, 2 mRNAs, and 42 miRNAs. Thus, we explained the potential interactions between KCNQ1OT1 and miR-421 with NR3C1 and XIAP genes. Conclusion: Our study represents potential prognostic biomarkers and a new ceRNA network for further study in CRC.

Phenotypicand Genotypic Characterization of Clinical Isolates of Intracellular Adherent-Invasive Escherichia coli Among Different Stages, Family History, and Treated Colorectal Cancer Patients in Iran.

There is increasing evidence showing that microbial dysbiosis impacts the health and cancer risk of the host. An association between adherent-invasive Escherichia coli (AIEC) and colorectal cancer (CRC) has been revealed. Cyclomodulins (CMs) have been receiving increasing attention for carcinogenic changes. In this study, the incidence and features of intracellular AIEC and cyclomodulin-encoding genes were investigated and the phylogenetic grouping and genetic relatedness were evaluated. E. coli strains were isolated from the colorectal biopsies. Adhesion and invasion assays and intramacrophage cell survival test were performed to separate the AIEC isolates. Virulence genotyping for the genes htrA, dsbA, chuA, and lpfA and the cyclomodulin toxins was also conducted. In addition, phylogenetic grouping of the isolates was determined. Subsequently, repetitive element sequence-based PCR (rep-PCR) fingerprinting was performed. A total of 24 AIEC pathovars were isolated from 150 patients. The prevalence rates of htr, dsbA, and lpfA were 70.83% and that of chuA was 91.66%. The frequencies of the cyclomodulin toxins were as follows: cnf1, 29.2%; cnf2, 25%; colibactin, 29.2%; and cdt, 4.2%; cif was not found. Among the AIEC isolates, 4.2%, 4.2%, 54.2%, 29.2%, and 8.3% with phylotypes A or C, B1, B2, D, and E were identified, respectively. Left-sided colon carcinoma and adenocarcinoma T≥1 stage (CRC2) were colonized by B2 phylogroup AIEC-producing CMs more often than the samples from the other groups. Close genetic relatedness was observed in AIEC isolates with rep-PCR.

Nrf2 signaling pathway in trace metal carcinogenesis: A cross-talk between oxidative stress and angiogenesis.

A large number of people worldwide are affected by chronic metal exposure, which is known to be associated with different type of malignancies. The mechanisms of metal carcinogenicity are complex in nature, and excessive reactive oxygen species (ROS) generation induced by chronic metal exposure, among the other factors, has been proposed as one of the major mechanisms involved in that process. In tumor cells, ROS buildup may lead to cell death through intrinsic and extrinsic signaling pathways. Furthermore, ROS-mediated redox signaling has a crucial role in angiogenesis, which is recognized as an essential step in tumor progression. There are several redox-modulating pathways and among them, the nuclear factor erythroid2-related factor2 (Nrf2), as a sensor of oxidative or electrophilic stress, has introduced as a master regulator of cellular response against environmental stresses. Activation of Nrf2 signaling induces expression of wide variety of antioxidant and detoxification enzymes genes. Thus, this transcription factor has recently received much attention as a target for cancer chemoprevention. But meanwhile, constitutive Nrf2 activation in cancerous cells may promote cancer progression and resistance to chemotherapy. The current review describes the major underlying mechanisms involved in carcinogenesis of trace metals: copper, silver, and cadmium, with a special focus on the Nrf2 signaling pathway as a crossroad between oxidative stress and angiogenesis.

Candida colonization of the esophagus and gastric mucosa; a comparison of patients taking proton pump inhibitors and those taking histamine receptor antagonist drugs.

AIM: Investigation of Candida colonization of the esophagus and gastric mucosa in patients taking proton pump inhibitors in comparison with those taking histamine-2 receptor antagonists. BACKGROUND: Candida species are normal flora of alimentary tract that can cause infection of the esophagus and gastro-intestinal tract in immunocompromised patients. Consumption of proton pump inhibitors and histamine-2 receptor antagonists has been shown to alter the gastric pH, which may predispose the esophagus and stomach to floral transmission and colonization. METHODS: Two hundred and forty-five clinical specimens were obtained from 91 patients who underwent endoscopy from September 2019 to February 2020. Direct microscopy with KOH 10% and subculture on sabouraud dextrose agar containing chloramphenicol was used as primary screening. PCR with ITS primers was performed to amplify the ITS1-5.8SrDNA-ITS2 region, and the MspI restriction enzyme was used for RFLP to identify clinical isolates. RESULTS: Seventy cultures out of 245 specimens were positive for Candida colonization (28.5%). Colonization of Candida species in gastric acid and gastric tissue biopsies of patients who took PPIs and H2 blockers was significantly higher than in those in the control group (p= 0.001). The use of ranitidine, pantoprazole, and omeprazole increased the risk of gastric candidiasis by 10.60, 9.20, and 12.99 times, respectively (p< 0.05). CONCLUSION: The use of PPIs and H2 blockers, ageing, and consumption of vegetables were main risk factors for gastric colonization in the present survey; other variables, such as Candida species, cigarette smoking, and alcohol consumption, were not implicated in the development of gastroesophageal lesions. Further investigations are necessary to understand how these predisposing factors change the host's defense mechanisms and increase colonization of fungi at mucosal surfaces.

Assessment of contrast sensitivity and aberrations after photorefractive keratectomy in patients with myopia greater than 5 diopters.

This study aimed to assess changes in contrast sensitivity and aberrations in cases of myopia greater than 5.0 diopter (D) who had photorefractive keratectomy (PRK). In this semi-experimental study, 20 eyes of ten patients were studied. Inclusion criteria were at least 5.0 D of myopia, stable refraction in the past year, no history of refractive surgery, a minimum corneal thickness of 480 µm, and having surgery in both eyes. Exclusion criteria were the presence of any corneal condition. In addition to the routine tests, aberrometry and assessment of contrast sensitivity was done using the WaveLight Allegro Analyzer and the VectorVision CSV-1000. After PRK using the Concerto Excimer Laser (WaveLight, Alcon), patients were scheduled to have follow-up visits at 1 month, 3 months, and 1 year after surgery. Contrast sensitivity with glare showed an increasing trend only at the spatial frequency of 3 cycles per degree (cpd) (P=0.013). Contrast sensitivity without glared increased postoperatively at special frequencies of 3, 6, and 18 cpd (P<0.05). The preoperative level of higher order aberrations root mean square (HOA RMS) of 0.24±0.08 reached 0.71±0.25 at 12 months after surgery. Assessment of comma and trefoil showed no significant difference between preoperative and postoperative values, but the amount of spherical aberration changed from a mean preoperative value of 0.0±0.09 to 0.27±0.15 at 12 months after surgery. In the treatment of myopia greater than 5.0 D, PRK with the Concerto Excimer Laser can improve contrast sensitivity in certain spatial frequencies. This is while HOA RMS and spherical aberration increase.

The Persian Wednesday Eve Festival "Charshanbe-Soori" fireworks eye injuries: a case series.

PURPOSE: To describe the clinical spectrum and severity of eye injuries sustained during the Persian Wednesday Eve Festival "Charshanbe-Soori" and to identify the fireworks devices involved. METHODS: Prospectively, consecutive patients treated for fireworks-related eye injuries in the emergency room at Farabi Eye Hospital, Tehran, over 3 days around the occasion in 2000, 2001, and 2002 were studied. RESULTS: Four hundred thirty-seven cases of eye injuries with an age range of 2-74 (median 17; SD 11.1) years were studied: 84.6% were male; 18.6% of the injuries were bilateral; 79.9% of the injured were bystanders or passersby. Eleven types of devices were involved, of which seven were explosives and eight were homemade. "Narenjaks," homemade grenades, were involved in 62.2%, firecrackers in 14.8%, and sparklers in 6.2% of the events. Injuries were categorized as severe in 49% of cases, and 45 (10.4%) people were hospitalized. Five eyes with no light perception and/or enucleation, 33 cases of monocular blindness, 54 (12.3%) cases of open globe (including intraocular foreign bodies) were observed. Grenades, bystander and passerby roles, outdoor context, a relatively older age, lower socioeconomic status, and male gender in the subset of passive roles were the determinants of more severe injuries (all p values < 0.05). Lid injuries (67.7%), corneal abrasions (51.6%), hyphema (48.1%), superficial foreign bodies (32.5%), and corneal contusions (13.8%) were the five leading injuries. CONCLUSIONS: In Iran, fireworks cause frequent and diverse injuries during the Wednesday Eve Festival and are a leading cause of severe eye injuries and monocular blindness.