Molecular epidemiology, antibiotic resistance profile and frequency of integron 1 and 2 in adherent-invasive Escherichia coli isolates of colorectal cancer patients.

This study explores the prevalence of adherent-invasive Escherichia coli (AIEC) in colorectal cancer (CRC) patients and investigates the potential of effective intracellular antibiotics as a therapeutic strategy for CRC patients with AIEC infections. Considering the pivotal role of integrons in bacterial antibiotic resistance, the frequency of class 1 and 2 integrons in AIEC isolated from CRC patients, in one of the referenced 3 gastroenterology clinics in Isfahan, Iran was examined. AIEC strains were isolated from the colorectal biopsies and their antimicrobial sensitivity was assessed using the disc diffusion method. Polymerase chain reaction (PCR) was employed to detect intl1 and intl2. The multilocus sequence typing (MLST) method was utilized to type 10 selected isolates. Of the 150 samples, 24 were identified as AIEC, with the highest number isolated from CRC2 (33.4%) and CRC1 (29.16%), and the least from the FH group (8.3%) and control group (12.5%). int1 in 79.2% and int2 in 45.8% of AIEC strains were found and 41.6% of strains had both integrons. AIEC isolates with int1 exhibited the highest sensitivity to trimethoprim-sulfamethoxazole (57.9%), while those with int2 showed the highest sensitivity to ciprofloxacin (63.6%). A significant association between resistance to rifampin and integron 2 presence in AIEC isolates was observed. Furthermore, a significant correlation between integron 1 presence, invasion, survival, and replication within macrophages in AIEC strains was identified. MLST analysis revealed ST131 from CC131 with integron 1 as the most common sequence type (ST). The emergence of such strains in CRC populations poses a serious public health threat. The distribution pattern of STs varied among studied groups, with pandemic STs highlighting the importance of examining and treating patients infected with these isolates. Comprehensive prospective clinical investigations are warranted to assess the prognostic value of detecting this pathovar in CRC and to evaluate therapeutic techniques targeting drug-resistant AIECs, such as phage therapy, bacteriocins, and anti-adhesion compounds, for CRC prevention and treatment.

Sperm Parameters and Chromatin Integrity in Men Suffering from Celiac Disease: Insights into Reproductive Health, Case-Control Study.

OBJECTIVE: Celiac disease is a common chronic inflammatory condition of the small intestine caused by permanent intolerance to gluten/gliadin. It has been demonstrated that oxidative stress is one of the mechanisms that is involved in gliadin toxicity, and there is a correlation between oxidative damage with this disease. Similarly, increased oxidative stress was repeatedly reported in infertile men which led to low-quality of sperm function. Therefore, we aimed to assess sperm parameters and chromatin status in men with Celiac disease. MATERIALS AND METHODS: In this case-control study, semen samples were collected from 11 fertile men without Celiac and 10 men with diagnostic Celiac disease. Basic semen analyses were performed according to the World Health Organization (WHO) 2010 protocol. The percentage of sperm with persistence histones, protamine deficiency, DNA fragmentation, malondialdehyde (MDA), and intracellular reactive oxygen species (ROS) were assessed using aniline blue, chromomycin A3, sperm chromatin structure assay, thiobarbituric acid reactive substances (TBARS) assay, and diacetyldichlorofluorescein staining, respectively. RESULTS: Unlike the sperm parameters, which did not show significant differences between men with Celiac disease and fertile individuals, sperm chromatin maturation (persistence histones and protamine deficiency) and sperm DNA damage in men with Celiac disease were significantly higher compared to fertile individuals (P<0.05). In addition, the percentage of sperm viability in these individuals was significantly lower than that in the fertile individuals (P<0.05). We did not observe any significant differences in sperm lipid peroxidation and intracellular ROS levels between the two study groups (P>0.05). CONCLUSION: Celiac disease affects sperm chromatin maturation and DNA fragmentation, emphasizing its impact on reproductive health.

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.

A pan-cancer analysis indicates long noncoding RNA HAND2-AS1 as a potential prognostic, immunomodulatory and therapeutic biomarker in various cancers including colorectal adenocarcinoma.

The HAND2-AS1 (HAND2 Antisense RNA 1) Long noncoding RNA (lncRNA) has emerged as a participant in the initiation of various cancer types, underscoring its pivotal involvement in both oncological processes and immune responses. To gain deeper insights into the functional nuances of HAND2-AS1 and identify novel avenues for cancer immunotherapy, a comprehensive evaluation of this gene was undertaken. Here, based on the co-expression network analysis and construction of interacting lncRNA-mRNA genes, we introduce the HAND2-AS1 lncRNA, emphasizing its key roles in tumorigenesis and immune regulation. Our study spans across 33 distinct cancer types, revealing the HAND2-AS1's aberrant expression patterns, methylation variations, mutational signatures, and immune engagement. Across a majority of tumors, HAND2-AS1 exhibited a propensity for down-regulation, remarkably an association with poor survival outcomes. The outcomes of functional enrichment analyses strongly suggest HAND2-AS1's engagement in tumor progression and its association with various immune pathways across diverse tumor classifications. Additionally, a positive correlation emerged between HAND2-AS1 expression and the infiltration levels of key immune cells, encompassing not only immunosuppressive entities such as tumor-associated macrophages, cancer-associated fibroblasts, and Tregs, but also immune effector cells like NK cells and CD8+ T cells, spanning a pan-cancer context. Furthermore, the differential expression of HAND2-AS1 appears to have downstream consequences on various pathways, thus implicating it as a potential regulator in diverse cancer types. Finally, we have employed CRC tumor and normal samples to carry out clinical validation of HAND2-AS1. Our study unveils HAND2-AS1's potential as a pan-cancer tumor suppressor, and its essential role in the tumorigenesis and immune surveillance. The increased HAND2-AS1 expression emerges as a promising candidate for prognostic evaluation, therapeutic strategy, and a focal point for immunotherapeutic interventions.

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.

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.

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.

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.

IS DAIRY FOODS RESTRICTION MANDATORY FOR INFLAMMATORY BOWEL DISEASE PATIENTS: A MULTINATIONAL CROSS-SECTIONAL STUDY.

BACKGROUND: The role of dairy foods in inflammatory bowel disease (IBD) has been controversial and it is debatable if patients with IBD should avoid milk and dairy products or not, as well as the relationship between these foods and symptoms among those population. OBJECTIVE: This multi centric cross-sectional study designed to evaluate if it is really necessary to deprive IBD patients from consumption of dairy foods. METHODS: A multicenter study with 12 gastroenterology referral centers in four countries was designed to evaluate gastrointestinal (GI) symptoms after consumption of dairy foods from all outpatients with IBD during 6 months and to compare patients treated at the same centers without IBD (non IBD cases). RESULTS: Overall 1888 cases included (872 IBD patients and 1016 non IBD cases). 56.6% of participants were female with average age of 40.1 years. Racially 79.8% participants were Caucasians and originally they were citizens of 10 countries. Relative prevalence of IBD was higher in Africans and Indians and the most frequent prevalence of dairy foods intolerance was seen in Asians. Among IBD patients, 571 cases diagnosed as ulcerative colitis and 189 participants as Crohn's disease. Average duration of diagnosis as IBD was 6.8 years (from 2 months to 35 years). The most prevalent GI symptoms after consumption of all the dairy foods were bloating and abdominal pain. Totally, intolerance of dairy foods and lactase deficiency was more prevalent among IBD patients in comparison with non IBD cases (65.5% vs 46.1%, P=0.0001). But the rate of GI complains among IBD patients who had not any family history of lactase deficiency, history of food sensitivity or both were 59.91%, 52.87% & 50.33% respectively and similar to non IBD cases (P=0.68, 0.98 & 0.99 respectively). CONCLUSION: The rate of dairy foods intolerance among IBD patients without family history of lactase deficiency or history of food sensitivity is similar to non IBD cases and probably there is no reason to deprive them from this important source of dietary calcium, vitamin D and other nutrients.

A restrição de alimentos lácteos é obrigatória para pacientes com doença inflamatória intestinal? Estudo transversal multinacional / Is dairy foods restriction mandatory for inflammatory bowel disease patients: a multinational cross-sectional study

ABSTRACT Background: The role of dairy foods in inflammatory bowel disease (IBD) has been controversial and it is debatable if patients with IBD should avoid milk and dairy products or not, as well as the relationship between these foods and symptoms among those population. Objective: This multi centric cross-sectional study designed to evaluate if it is really necessary to deprive IBD patients from consumption of dairy foods. Methods: A multicenter study with 12 gastroenterology referral centers in four countries was designed to evaluate gastrointestinal (GI) symptoms after consumption of dairy foods from all outpatients with IBD during 6 months and to compare patients treated at the same centers without IBD (non IBD cases). Results: Overall 1888 cases included (872 IBD patients and 1016 non IBD cases). 56.6% of participants were female with average age of 40.1 years. Racially 79.8% participants were Caucasians and originally they were citizens of 10 countries. Relative prevalence of IBD was higher in Africans and Indians and the most frequent prevalence of dairy foods intolerance was seen in Asians. Among IBD patients, 571 cases diagnosed as ulcerative colitis and 189 participants as Crohn's disease. Average duration of diagnosis as IBD was 6.8 years (from 2 months to 35 years). The most prevalent GI symptoms after consumption of all the dairy foods were bloating and abdominal pain. Totally, intolerance of dairy foods and lactase deficiency was more prevalent among IBD patients in comparison with non IBD cases (65.5% vs 46.1%, P=0.0001). But the rate of GI complains among IBD patients who had not any family history of lactase deficiency, history of food sensitivity or both were 59.91%, 52.87% & 50.33% respectively and similar to non IBD cases (P=0.68, 0.98 & 0.99 respectively). Conclusion: The rate of dairy foods intolerance among IBD patients without family history of lactase deficiency or history of food sensitivity is similar to non IBD cases and probably there is no reason to deprive them from this important source of dietary calcium, vitamin D and other nutrients.

RESUMO Contexto: O papel dos alimentos lácteos na doença inflamatória intestinal (DII) tem sido controverso e é discutível se os pacientes com DII devem ou não evitar leite e laticínios, bem como a relação entre esses alimentos e sintomas nesta população. Objetivo: Estudo transversal multicêntrico foi projetado para avaliar se é realmente necessário privar os pacientes com DII do consumo desta classe de alimentos. Métodos: Um estudo multicêntrico com 12 centros de referência em gastroenterologia de quatro países foi projetado para avaliar sintomas gastrointestinais após o consumo de alimentos lácteos em todos os ambulatórios de DII durante seis meses e comparar pacientes tratados nos mesmos centros sem DII. Resultados: No total, foram incluídos 1888 casos (872 pacientes com DII e 1016 casos sem DII. 56,6% dos participantes eram do sexo feminino com idade média de 40,1 anos. 79,8% dos participantes eram caucasianos e originalmente eram cidadãos de 10 países. A prevalência relativa de DII foi maior em africanos e indianos e a prevalência mais frequente de intolerância a alimentos lácteos observada nos asiáticos. Entre os pacientes com DII, 571 casos foram diagnosticados como colite ulcerativa e 189 participantes como doença de Crohn. A duração média do diagnóstico como DII foi de 6,8 anos (de 2 meses a 35 anos). Os sintomas de gastrointestinais mais prevalentes após o consumo de todos os alimentos lácteos foram inchaço e dor abdominal. No total, a intolerância aos alimentos lácteos e a deficiência de lactase foi mais prevalente entre os pacientes com DII em comparação com os casos sem DII (65,5% vs 46,1%, P=0,0001). A taxa de queixas gastrointestinais entre os pacientes com DII que não tinham histórico familiar de deficiência de lactase, histórico de sensibilidade alimentar ou ambos foram de 59,91%, 52,87% e 50,33% respectivamente e semelhantes aos casos sem DII (P=0,68, 0,98 e 0,99, respectivamente). Conclusão: A taxa de intolerância de alimentos lácteos entre pacientes com DII sem histórico familiar de deficiência de lactase ou histórico de sensibilidade alimentar é semelhante aos casos sem DII e provavelmente não há razão para privá-los dessa importante fonte de cálcio dietético, vitamina D e outros nutrientes.

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.

Calcium and dairy products in the chemoprevention of colorectal adenomas: a systematic review and meta-analysis.

The risk of transition to colorectal cancer (CRC) in advanced colorectal adenomas (ACAs) is about 2.5 times higher than the non-advanced ones. This systematic review and meta-analysis was performed to determine the effect of calcium and dairy products on the incidence of CAs and ACAs. Six databases were systematically searched and 37 relevant clinical trials and observational studies involving over 10,964 cases were selected for inclusion. The results showed that calcium consumption reduced the risk of CAs incidence by 8% (RR: 0.92; 95% CI: 0.89-0.96), and calcium intake as a food and dairy product reduced it about 21% (RR: 0.79; 95% CI: 0.72-0.86), and 12% (RR: 0.88; 95% CI: 0.78-0.98), respectively. However, calcium supplementation did not show a significant effect on CAs incidence (RR: 0.97; 95% CI: 0.89-1.05). Results also revealed that total calcium intake markedly reduced the risk of ACAs (RR: 0.79; 95% CI: 0.73-0.85) and the risk of recurrence of adenomas about 12% (RR: 0.88; 95% CI: 0.84-0.93). Our results suggest that natural sources of calcium such as dairy products and foods may have more effective role than supplementary calcium in terms of reducing the risk of incidence and recurrence of colorectal adenomas and advanced adenomas.

Prevalence of Mismatch Repair-Deficient Colorectal Adenoma/Polyp in Early-Onset, Advanced Cases: a Cross-Sectional Study Based on Iranian Hereditary Colorectal Cancer Registry.

BACKGROUND: Lynch syndrome (LS) increases the risk of many types of cancer, mainly colorectal cancer (CRC). The purpose of this study was to assess the prevalence of mismatch repair (MMR) deficiency in patients under the age of 50 with advanced adenomatous polyps, aiming at an early diagnosis of LS. METHODS: This retrospective, cross-sectional study included eligible patients with advanced adenomas diagnosed ≤ 50 years of age registered between April 2014 and February 2017 at three pathology centers in Mashhad. Pathological records were reviewed, and colon tissue specimens were analyzed by immunohistochemistry (IHC) staining to identify proteins which serve as markers for LS as they are related to loss of MMR gene (MLH1, MSH2, MSH6, and PMS2) expression. RESULTS: Of 862 consecutive patients, a total of 50 adenomas (54% males, 46% females of mean age 41.24 ± 6.5) met the eligibility criteria. Of the adenomas examined, 20 (40%) had a tubulovillous component, 34 (68%) had high-grade dysplasia, and 30 (60%) had were larger than 10 mm protrusions. None of the patients had loss of MMR protein expression. CONCLUSION: No individual with MMR genetic disorder was identified by IHC screening of early-onset advanced colorectal adenomas. This strategy is therefore not an effective strategy for detecting MMR mutation carriers.

Eugenol Administration Improves Liver Damage Induced by a Fructose-Rich Diet.

BACKGROUNDS: The prevalence of metabolic syndrome (MetS) is increasing in developing countries that affects the liver in a variety of ways. This study was designed to investigate the protective role of eugenol on liver damage caused by fructose-induced MetS. MATERIALS AND METHODS: Thirty male Wistar rats were randomly divided into five groups: 1: tap water (control), 2: fructose, 3: fructose + eugenol solvent, 4: fructose + eugenol 50 mg/kg, and 5: fructose + eugenol 100 mg/kg. At the end of the experiment, blood samples were taken for measurement fast blood glucose (FBG), serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), low-density lipoprotein, high-density lipoprotein, cholesterol, and triglyceride. RESULTS: FBG significantly increased in Group 2 compared to Group 1 (P < 0.001); however, it significantly decreased in Groups 4 and 5 compared to Group 2 (P < 0.05). SGOT and SGPT levels significantly increased in Group 2 compared to the control group (P < 0.001). However, SGOT and SGPT levels significantly decreased in Groups 4 and 5. Malondialdehyde (MDA) and liver tissue damage score (LTDS) significantly increased in Group 2 compared with the control group (P < 0.01), whereas MDA and LTDS decreased in Groups 4 and 5 compared to Group 2 (P < 0.05). CONCLUSION: Eugenol may ameliorate liver damage in a rat model of fructose-induced MetS, and these protective effects may in part be mediated by improving antioxidant status and reducing oxidative stress and lipid peroxidation. It may also reduce hepatic inflammation and fat accumulation as well as fibrosis of liver cells.

A Review on the Phytochemistry, Pharmacology, and Therapeutic Effects of Rheum ribes.

Herbal medications are typically used for the treatment of diverse diseases without significant adverse effects. The Rheum ribes (R. ribes), commonly called rhubarb, is a hardy perennial herb and is consumed all over the world. There is growing evidence of the therapeutic benefits of R. ribes. Extensive in vitro and in vivo investigations have shown that R. ribes reveals beneficial properties via different mechanisms. In the current article, various pharmacological and therapeutic effects of R. ribes have been reviewed. For this purpose, different online databases using keywords such as R. ribes, therapeutic effects, and pharmacological effects were searched until the end of December 2020. R. ribes has been suggested to be effective in the treatment of a wide range of disorders including stomachache, nausea and vomiting, hemorrhoids, and measles. Additionally, different studies have demonstrated that R. ribes possesses numerous pharmacological properties including anti-inflammatory, anticancer, antibacterial, and antiviral, and may also function as an expectorant. The present narrative review provides a detailed survey of scientific investigations regarding the pharmacological properties and therapeutic effects of R. ribes.

Gastrointestinal and renal complications in SARS-CoV-2-infected patients: Role of immune system.

The recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease has been accompanied by various gastrointestinal (GI) and renal manifestations in significant portion of infected patients. Beside studies on the respiratory complications of coronavirus infection, understanding the essential immunological processes underlying the different clinical manifestations of virus infection is crucial for the identification and development of effective therapies. In addition to the respiratory tract, the digestive and urinary systems are the major sources of virus transmission. Thus, knowledge about the invasion mechanisms of SARS-CoV-2 in these systems and the immune system responses is important for implementing the infection prevention strategies. This article presents an overview of the gut and renal complications in SARS-CoV-2 infection. We focus on how SARS-CoV-2 interacts with the immune system and the consequent contribution of immune system, gut, and renal dysfunctions in the development of disease.

Sex Difference in Gentamicin-induced Nephrotoxicity: Influence of L-arginine in Rat Model.

BACKGROUND: L-arginine is an important precursor for the formation of nitric oxide (NO). According to previous studies, NO function is related to gender. Likewise, chronic renal diseases have lower prevalence in female. Gentamicin (GM) is an aminoglycoside antibiotic. According to some studies, males are more sensitive to GM renal nephrotoxicity. This study attempts to find protective effects of L-arginine on GM nephrotoxicity in male and female rats. METHODS: Male and female rats were divided into eight groups: Rats were randomly assigned to 8 groups each including both male and female rats. The first and second groups received vehicle (saline), the third and fourth groups received gentamicin (80 mg/kg), the fifth and sixth groups received L-arginine (150 mg/kg), and finally, seventh and eighth groups received gentamicin+ L- arginine. Next, 9 days after administering drugs, blood samples were collected from the heart. After making sacrifices, the level of blood urea, creatinine (Cr), nitrite, and malondialdehyde (MDA) was measured in serums. Likewise, nitrite and MDA were measured in the homogenized kidney tissue. RESULTS: GM significantly increased serum level of urea and Cr in male and female rats (P < 0.05). However, co-administration of GM + L-arginine significantly did not decrease urea and Cr level in male rats, whereas, in female rats, they significantly reduced (P < 0.05). In response to GM, renal MDA level increased in male and female rats (P < 0.05), and in the presence of GM + L-arginine, the level of MDA significantly decreased in both genders (P < 0.05). CONCLUSIONS: L-arginine demonstrated some protective effects in female rats but did not protect against GM nephrotoxicity in male rats for unknown reasons, probably related to the effects of sex hormones which needs further studies to be confirmed.

Effects of sex steroid hormones on neuromedin S and neuromedin U2 receptor expression following experimental traumatic brain injury.

OBJECTIVES: Neuroprotective effects of female gonadal steroids are mediated through several pathways involving multiple peptides and receptors after traumatic brain injury (TBI). Two of these peptides are including the regulatory peptides neuromedin U (NMU) and neuromedin S (NMS), and their common receptor neuromedin U2 receptor (NMUR2). This study investigates the effects of physiological doses of estradiol and progesterone on brain edema, NMS and NMU as well as NMUR2 expression following TBI. MATERIALS AND METHODS: Ovariectomized female rats were given high-and low-dose of female sex steroid hormones through implantation of capsules for a week before trauma. The brain NMUR2 expression, prepro-NMS expression, NMU content, and water content (brain edema) were evaluated 24 hr after TBI induced by Marmarou's method. RESULTS: Percentage of brain water content in high- and low-dose estradiol, and in high- and low- dose progesterone was less than vehicle (P<0.01). Results show high expression of prepro-NMS in high dose progesterone (TBI-HP) rats compared to the high dose estrogen (TBI-HE), as well as vehicle (P<0.01). NMU content in low-dose progesterone (TBI-LP) group was more than that of vehicle group (P<0.001). Furthermore a difference in NMU content observed between TBI-HP compared to TBI-HE, and vehicle (P<0.05). The NMUR2 mRNA expression revealed an upregulation in TBI-HP rats compared to the TBI-HE group (P<0.001). CONCLUSION: Findings indicate that progesterone attenuates brain edema and induces an increase in NMS and its receptor which may mediate the anti-edematous effect of progesterone after TBI.

Estrogen provides neuroprotection against brain edema and blood brain barrier disruption through both estrogen receptors α and ß following traumatic brain injury.

OBJECTIVES: Estrogen (E2) has neuroprotective effects on blood-brain-barrier (BBB) after traumatic brain injury (TBI). In order to investigate the roles of estrogen receptors (ERs) in these effects, ER-α antagonist (MPP) and, ER-ß antagonist (PHTPP), or non-selective estrogen receptors antagonist (ICI 182780) were administered. MATERIALS AND METHODS: Ovariectomized rats were divided into 10 groups, as follows: Sham, TBI, E2, oil, MPP+E2, PHTPP+E2, MPP+PHTPP+E2, ICI+E2, MPP, and DMSO. E2 (33.3 µg/Kg) or oil were administered 30 min after TBI. 1 dose (150 µg/Kg) of each of MPP, PHTPP, and (4 mg/kg) ICI182780 was injected two times, 24 hr apart, before TBI and estrogen treatment. BBB disruption (Evans blue content) and brain edema (brain water content) evaluated 5 hr and 24 hr after the TBI were evaluated, respectively. RESULTS: The results showed that E2 reduced brain edema after TBI compared to vehicle (P<0.01). The brain edema in the MPP+E2 and PHTPP+E2 groups decreased compared to the vehicle (P<0.001). There was no significant difference in MPP+PHTPP+E2 and ICI+E2 compared to TBI. This parameter in MPP was similar to vehicle. Evans blue content in E2 group was lower than vehicle (P<0.05). The inhibitory effect of E2 on Evans blue was not reduced by MPP+E2 and PHTPP+E2 groups, but decreased by treatment with MPP+PHTPP or ICI. MPP had no effect on Evans blue content. CONCLUSION: A combined administration of MPP and PHTPP or ICI inhibited the E2-induced decrease in brain edema and BBB disruption; this may suggest that these effects were mediated via both receptors.