Escherichia coli cytosine deaminase: Structural and biotechnological aspects.

Suicide gene therapy involves introducing viral or bacterial genes into tumor cells, which enables the conversion of a nontoxic prodrug into a toxic-lethal drug. The application of the bacterial cytosine deaminase (bCD)/5-fluorocytosine (5-FC) approach has been beneficial and progressive within the current field of cancer therapy because of the enhanced bystander effect. The basis of this method is the preferential deamination of 5-FC to 5-fluorouracil by cancer cells expressing cytosine deaminase (CD), which strongly inhibits DNA synthesis and RNA function, effectively targeting tumor cells. However, the poor binding affinity of toward 5-FC compared to the natural substrate cytosine and/or inappropriate thermostability limits the clinical applications of this gene therapy approach. Nowadays, many genetic engineering studies have been carried out to solve and improve the activity of this enzyme. In the current review, we intend to discuss the biotechnological aspects of Escherichia coli CD, including its structure, functions, molecular cloning, and protein engineering. We will also explore its relevance in cancer clinical trials. By examining these aspects, we hope to provide a thorough understanding of E. coli CD and its potential applications in cancer therapy.

Dietary protein intake and mortality among survivors of liver cirrhosis: a prospective cohort study.

BACKGROUND: Liver cirrhosis is a worldwide burden and is associated with poor clinical outcomes, including increased mortality. The beneficial effects of dietary modifications in reducing morbidity and mortality are inevitable. AIM: The current study aimed to evaluate the potential association of dietary protein intake with the cirrhosis-related mortality. METHODS: In this cohort study, 121 ambulatory cirrhotic patients with at least 6 months of cirrhosis diagnosis were followed-up for 48 months. A 168-item validated food frequency questionnaire was used for dietary intake assessment. Total dietary protein was classified as dairy, vegetable and animal protein. We estimated crude and multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), applying Cox proportional hazard analyses. RESULTS: After full adjustment for confounders, analyses showed that total (HR = 0.38, 95% CI = 0.2-1.1, p trend = 0.045) and dairy (HR = 0.38, 95% CI = 0.13-1.1, p trend = 0.046) protein intake was associated with a 62% lower risk of cirrhosis-related mortality. While a higher intake of animal protein was associated with a 3.8-fold increase in the risk of mortality in patients (HR = 3.8, 95% CI = 1.7-8.2, p trend = 0.035). Higher intake of vegetable protein was inversely but not significantly associated with mortality risk. CONCLUSION: A comprehensive evaluation of the associations of dietary protein intake with cirrhosis-related mortality indicated that a higher intakes of total and dairy protein and a lower intakes of animal protein are associated with a reduced risk of mortality in cirrhotic patients.

Changes in c-fos and p-CREB signaling following exposure to forced swim stress or exogenous corticosterone during morphine-induced place preference are dependent on glucocorticoid receptor in the basolateral amygdala.

Neural circuitry comprising the nucleus accumbens (NAc), prefrontal cortex (PFC), amygdala (AMY), and hippocampus (HIP) are the main components of the reward circuit. Our previous behavioral data showed that forced swim stress (FSS) and corticosterone administration could inhibit the acquisition of morphine-induced conditioned place preference (CPP), and this effect was blocked by intra-basolateral amygdala (BLA) administration of RU38486, glucocorticoid receptor (GR) antagonist. Therefore, we tried to evaluate the effect of intra-BLA administration of the GR antagonist during the conditioning phase on the c-fos and p-CREB/CREB ratio expression in the AMY, NAc, PFC, and HIP of rats that underwent FSS or received exogenous corticosterone (10 mg/kg; i.p.) before morphine injection (5 mg/kg; s.c.) during 3 conditioning days. Our results showed that morphine-induced CPP could increase c-fos level and p-CREB/CREB ratio in all regions (except in the HIP). In addition, c-fos expression was elevated by FSS in all regions and blockade of GR decreased this effect. In the PFC, in addition to FSS, corticosterone could raise c-fos expression, which was blocked by RU38486. In conclusion, it seems that the intra-BLA administration of RU38486 differently modulates the effect of morphine-induced CPP on the expression of c-fos and p-CREB/CREB ratio in animals that underwent FSS or corticosterone administration.

The effects of two vitamin D regimens on ulcerative colitis activity index, quality of life and oxidant/anti-oxidant status.

BACKGROUND: The optimum dosage for vitamin D supplementation has not yet been elucidated in patients with Ulcerative colitis (UC). The aim of this study was to investigate the effects of two vitamin D regimens in UC patients with vitamin D deficiency. METHODS: In this double blind randomized clinical trial, 50 patients with mild to moderate UC, who met inclusion criteria, received either 1000 or 2000 IU/day of vitamin D (as low dose or high dose group, respectively) for 12 weeks. Serum 25-hydroxy vitamin D (25-OHD) level, total antioxidant capacity (TAC), and Total Oxidant Status (TOS), the inflammatory bowel disease questionnaire - 9 (IBDQ-9) score and the Simple Clinical Colitis Activity Index Questionnaire (SCCAI) score were assessed before and after intervention. RESULTS: At the end of study, serum 25-OHD levels significantly increased in the high dose group (P < 0.001) and the increase was significantly more than low dose group (6.7 ± 3.8 ng/mL in the high dose group versus 0.2 ± 0.5 ng/mL in the low dose group) (P < 0.001). Serum TOS concentration decreased significantly (- 0.37 ± 0.26) only in the high dose group (P value = 0.023). There was no statistically significant change in serum TAC between two groups during the study. IBDQ-9 mean score significantly increased in high dose group compared to the low dose group (P value = 0.001) and SCCAI score in both groups reduced (- 2.58 ± 2.16 and - 0.9 ± 0.3 in high dose and low dose respectively), while this reduction was significant only in the high dose group (P value ≥0.001). CONCLUSION: Our results indicate that 2000 IU daily dose of vitamin D can increase serum 25-OHD concentration, and quality of life, while it reduces disease activity in UC patients with vitamin D deficiency. We recommend assessment of the vitamin D status in all patients with UC because they may benefit from vitamin D therapy.

The association of dietary patterns and adherence to WHO healthy diet with metabolic syndrome in children and adolescents: Tehran lipid and glucose study.

BACKGROUND: The optimal dietary pattern for reducing the extent of metabolic syndrome (MetS) has not been well established yet. The aim of this study was to evaluate dietary patterns and adherence to WHO healthy diet in children and adolescents and their associations with MetS. METHODS: Subjects of this cohort study were selected from among children and adolescents of the Tehran Lipid and Glucose Study participants, aged 6-18 years (n = 424). Dietary measurements were collected using a valid and reliable food frequency questionnaire. MetS was defined as the existence of at least 3 risk factors according to the Cook criteria. Diet was assessed based on dietary components of the WHO healthy diet. Dietary patterns were defined by principal component analysis. RESULTS: The mean ± SD age of participants (42% boys and 57% girls) was 13.5 ± 3.7 years. The most consistency with the WHO healthy diet was observed for cholesterol, free sugar and protein consumption in both genders, and the least was for n-3 poly-unsaturated fatty acid, trans-fatty acid and salt. Intake of SFA up to 12% of energy intake (third quartile) reduced the risk of MetS, compared to the first quartile. Subjects in the third quartile of n-6 poly-unsaturated fatty acid intake (6.2% of energy) showed the lowest odds ratio of MetS compared to the first quartile (OR: 0.18, CI: 0.04-0.66). In the adjusted model, the risk of MetS reduced across quartiles of MUFA intake by 60% (OR: 1, 0.40, 0.40, 0.42; P trend = 0.05). No significant trends were observed in the risk of MetS components across quartiles of the WHO healthy diet components. Three major dietary patterns were identified, the healthy, unhealthy and cereal/meat. An increased risk of MetS was observed in the highest quartile of unhealthy dietary pattern score compared to the lowest quartile (OR: 1, 0.81, 0.93, 2.49; P trend = 0.03). CONCLUSIONS: Our results demonstrated that the majority of our population did not meet some components of WHO healthy diet recommendations. The quality and quantity of fatty acid intakes were associated with risk of MetS. Adherence to unhealthy dietary pattern was associated with two-fold increase in MetS risk.

Reversible inactivation of the lateral hypothalamus reversed high reward choices in cost-benefit decision-making in rats.

The Lateral hypothalamus (LH) is an important component of the networks underlying the control of feeding and other motivated behaviors. Cost-benefit decision-making is mediated largely by the prefrontal cortex (PFC) which strongly innervates the LH. Therefore, in the current study, we conducted a series of experiments to elucidate the role of the perifornical area of the lateral hypothalamus (PeF-LH) in effort and/or delay-based decision-making. We trained different groups of rats in a delay-based and/or an effort-based form of cost-benefit T-maze decision- making task in which they could either choose to pay the cost to obtain a high reward in one arm or could obtain a low reward in the other arm with no cost. During test days, the rats received local injections of either vehicle or lidocaine4% (0.5 µl/side), in the PeF-LH. In an effort-based decision task, PeF-LH inactivation led to decrease in high reward choice. Similarly, in a delay-based decision task animals' preference changed to a low but immediately available reward. This was not caused by a spatial memory or motor deficit. PeF-LH inactivation modified decision behavior. The results imply that PeF-LH is important for allowing the animal to pay a cost to acquire greater rewards.

Effects of Temporary Inactivation and Electrical Stimulation of the Dorsal Raphe Nucleus on Morphine-induced Conditioned Place Preference.

BACKGROUND: The dorsal raphe nucleus (DRN) influences a wide range of behavioral and reward function. In this study, we evaluated electrical stimulation and inactivation of DRN on morphine conditioned place preference (CPP). METHODS: The rats were anesthetised (n = 7 for each group) and the electrode and cannula were implanted into the DRN by stereotaxic instrument. Electrical stimulation (100µA) and reversible inactivation by lidocaine were induced into DRN and then morphine-induced CPP was investigated. RESULTS: The stimulation of DRN in combination with effective dose of morphine showed a significant decrease only on expression phases 20s (SD 33.7) when compared with morphine group 119.85s (SD 23.7) (One way ANOVA, Tukey's; P = 0.036). Also, this stimulation in combination with ineffective dose of morphine showed a significant increase only on acquisition phases 67.5s (SD 41.2) of CPP compared with morphine group -46s (SD 18.51) (P = 0.034). Also, there were not significant differences in inactivation of DRN by lidocaine on different phase of CPP (P = 0.091) CONCLUSION: It is possible that electrical stimulation of the DRN with changes in concentration of serotonin or involving other transmitters such as glutamate and gamma amino butyric acid (GABA) would be involved to these changes of CPP.

Effect of chitosomes loaded zein on physicochemical, mechanical, microbial, and sensory characteristics of probiotic Kashk during cold storage.

Functional foods like probiotics offer health benefits against various diseases, and plant bioactive compounds can enhance their growth. Zein, a protein, shows biological activity upon hydrolysis, and encapsulating it in nanoparticles improves bioavailability. This study examined chitosan-coated nanoliposomes as carriers for hydrolyzed and unhydrolyzed maize zein to fortify kashk. Combining chitosan and hydrolyzed zein in a 1:2 ratio achieves the highest encapsulation efficiency, antioxidant activity, smallest particle size, polydispersity index, and zeta potential. FTIR and XRD analyses confirm hydrolyzed zein's entrapment and crystalline nature post-encapsulation. Optimized nanoliposomes release hydrolyzed zein faster in simulated intestinal fluid than in gastric fluid, indicating high bioavailability and stability. When used to fortify kashk, these nanoliposomes slightly lower acidity but maintain standard pH over 60-day cold storage, improve elastic properties, and enhance probiotic viability. At the same time, sensory attributes remain comparable to the control, highlighting their functional food potential.

Dietary Approaches to Stop Hypertension (DASH) and mortality risk among patients with liver cirrhosis: a prospective cohort study.

BACKGROUND AND PURPOSE: The relationship between dietary patterns and cirrhosis is undeniable. The present study aimed to investigate the association between the Dietary Approaches to Stop Hypertension (DASH) diet and the risk of mortality in patients with cirrhosis prospectively. METHODS: In this cohort study, 121 cirrhotic patients were enrolled and followed up annually for four years. Nutritional status and dietary intakes were assessed initially, and the DASH score was calculated accordingly. Crude and multivariable-adjusted hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox proportional hazard analyses. RESULTS: DASH components including fruits, vegetables, legumes, nuts and seeds, and low-fat dairy products were significantly associated with lower mortality risk in cirrhotic patients. Also, a higher DASH score was significantly associated with a reduction in the risk of mortality in patients with cirrhosis, so that after adjusting for all confounders, the risk of mortality in the upper tertile was 89% lower than the first tertile (HR = 0.11, 95% CI: 0.03-0.42, P trend < 0.001). The 4-year survival rate among patients across tertiles of DASH was 32%, 37%, and 46%, respectively (P = 0.005). CONCLUSION: It can be concluded that a higher DASH diet score may be associated with a reduced risk of mortality in cirrhotic patients. However, larger studies are needed to confirm the findings and determine their potential mechanisms.

Dietary acid load and cirrhosis-related mortality: a prospective cohort study.

As a global health concern, cirrhosis contributes significantly to morbidity and mortality. This prospective cohort study aimed to investigate the association between dietary acid load (DAL) and cirrhosis-related mortality. Present study was conducted on 121 patients with newly diagnosed cirrhosis who were followed up for 48 months. Anthropometric measures, nutritional status and dietary intakes were assessed and DAL was estimated based on potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores. Crude and multivariable-adjusted hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox proportional hazard analyses. Participants in the high PRAL and NEAP scores had significantly higher intakes of grains and lower intakes of fruits and vegetables. Also, the intake of dairy products and legumes, nuts and seeds decreased significantly with increasing NEAP score. After adjustment of all the confounders, the risk of mortality in the second and third tertiles of PRAL was 5.9 times and 10.97 higher than those in the first tertile, respectively (P trend: 0.006). Similarly, comparing the risk of mortality in the second and third tertiles with the first tertile of NEAP showed a 4.46-fold and 12.3-fold increased risk, respectively (P trend: 0.010). Our findings suggested that DAL was significantly associated with cirrhosis-related mortality and highlight the need for further research to understand the underlying mechanisms and establish optimal DAL levels in cirrhotic patients.

Dietary fiber intake and mortality among survivors of liver cirrhosis: A prospective cohort study.

Background: Liver cirrhosis is associated with significant nutritional risks and poor survival rates. Little is known about the impact of dietary factors on metabolic complications and mortality from cirrhosis. Aim: The present study investigated the potential associations between dietary fibers and the risk of cirrhosis-related mortality. Methods: In this prospective study, 121 ambulatory cirrhotic patients with more than six months of cirrhosis diagnosis were followed-up for 4 years. Dietary intakes were assessed using a 168-item semi-quantitative validated food frequency questionnaire. Crude and multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated through cox proportional hazards regression models. Results: Comparing the highest versus the lowest tertile, soluble and insoluble fiber intake was associated with 62% (HR = 0.38, 95% CI = 0.045-3.5, p trend = 0.047) and 73% (HR = 0.27, 95% CI = 0.06-1.2, p trend = 0.021) lower mortality risk, respectively, after full adjustment for potential confounders. Higher intakes of total fiber were inversely but non-significantly associated with mortality risk. Conclusion: Comprehensive assessment of dietary fiber intake associations with cirrhosis-related mortality showed that higher intakes of soluble and insoluble fiber were significantly associated with reduced mortality risk.

Investigation of the frequencies of various B cell populations in non-responder healthcare workers in comparison with responders to hepatitis B virus vaccination.

BACKGROUND: Hepatitis B is a major global health problem. More than 90% of hepatitis B-vaccinated immunocompetent adults become fully immune. The main purpose of vaccination is immunization. Whether non-responders have a lower percentage of total or antigen-specific memory B cells in comparison with responders is still controversial. We aimed to assess and compare the frequency of various B cell subpopulations in non-responders and responders. METHODS: Fourteen responders and 14 non-responders of hospital healthcare workers were enrolled in this study. We used flow cytometry to evaluate various CD19+ B cell subpopulations using fluorescent-labeled antibodies against CD19, CD10, CD21, CD27 and IgM and ELISA to evaluate total anti-HBs antibodies. RESULTS: We found no significant differences in the frequency of various B cell subpopulations between the non-responder and responder groups. Furthermore, the frequency of the isotype-switched memory B cell population was significantly higher in the atypical memory B cell subset compared with the classical memory B cell subset in the responder and total groups (p=0.010 and 0.003, respectively). CONCLUSIONS: Responders and non-responders to HBsAg vaccine had comparable memory B cell populations. Whether anti-HBs Ab production has a correlation with the level of class switching in B lymphocytes in healthy vaccinated individuals needs further investigation.

The association of dietary approach to stop hypertension (DASH) diet with hospitalization risk in patients with COVID-19.

Background and aim: Given the importance of dietary habits in the immune system, the current study aimed at investigating the association between Dietary Approach to Stop Hypertension (DASH) diet and risk of hospitalization due to COVID-19. Methods: Dietary data of 141 patients with COVID-19 were collected using 147-item food frequency questionnaire. DASH score in this cross-sectional study was calculated based on eight components, including fruits, vegetables, legumes and nuts and seeds, whole grains, low-fat dairy, red or processed meats, sweetened beverages, and sodium. Multivariable logistic regression models were applied to estimate the OR and 95% CI for hospitalization due to COVID-19 in each tertile of DASH score. Results: Mean ± SD of DASH score in inpatients (n=74) and outpatients (n= 87) was 22.5 ± 4.57 and 25.34 ± 4.23, respectively. The risk of hospitalization in the highest tertile of DASH score was 81% lower than the lowest tertile (OR=0.19, 95%CI: 0.07-0.55, P trend = 0.001 after adjustment for age, sex, BMI, energy intake). Also, more intake of fruits, vegetables and low-fat dairy products and less intake of sodium, red and processed meat were each significantly associated with reduced risk of hospitalization due to COVID-19. Conclusions: Our data provide evidence that adherence to DASH-style diet was associated with lower risk of hospitalization due to COVID-19.

Factors related to hypermetabolism in individuals with type 2 diabetes mellitus and non-alcoholic fatty liver disease.

Considering the progressive prevalence and co-occurrence of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD), as well as the current evidence suggesting the elevated levels of basal metabolic rate (BMR) among these individuals, the present study aimed to identify factors determining hypermetabolism in such subjects. This cross sectional study was conducted in 30 to 53-year-old individuals with concurrent T2DM and NAFLD (controlled attenuation parameter score ≥ 260 dB/m). Resting energy expenditure (REE) was determined by an indirect calorimetry device. Hypermetabolism was defined as an elevated measured REE > 110% of the predicted REE. The multivariate logistic regression test was used for detecting factors associated with hypermetabolism. Between September, 2017, and March, 2018, a total of 95 eligible participants (64.40% male) with both T2DM and NAFLD were included, while 32.63% of them were classified as hypermetabolic. Overall, the mean recruitment age ± standard deviation and median (interquartile range) body mass index were 44.69 ± 5.47 years and 30.20 (27.80-33.30) kg/m2, respectively. Demographic, anthropometric and biochemical variables did not vary significantly across two groups except for total body water, low-density lipoprotein cholesterol and dipeptidyl peptidase 4 (DPP-4) inhibitors (p < 0.05). According to the results of multivariable logistic regression analyses, hypermetabolism had a positive association with adiponectin (odds ratio [OR] 1.167, 95% confidence interval [CI] 1.015-1.342, p = 0.030), physical activity (OR 1.134, 95% CI 1.002-1.284, p = 0.046), alanine transaminase (OR 1.062, 95% CI 1.006-1.122, p = 0.031) and diastolic blood pressure (OR 1.067, 95% CI 1.010-1.127, p = 0.021). However, fat free mass was inversely related to hypermetabolism (OR 0.935, 95% CI 0.883-0.991, p = 0.023). Adiponectin, alanine transaminase, physical activity, diastolic blood pressure and fat free mass were independently associated with hypermetabolism in subjects with NAFLD and T2DM.

Relationship Between Dairy Intake and Hospitalization Risk and Disease Severity in Patients With COVID-19.

The aim of this study was to investigate whether dairy intake was associated with the severity of coronavirus disease 2019 (COVID-19) disease and the probability of hospitalization of patients. This cross-sectional study was conducted on 141 patients with COVID-19 with an average age of 46.23 ± 15.88 years. The number of men (52.5%) participating in this study was higher than that of women. The association between dairy intake and COVID-19 was evaluated by multivariable logistic regression analysis. The risk of hospitalization in the highest tertile of dairy intake was 31% lower than in the lowest tertile (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.37-1.25, p trend = 0.023). Higher milk and yogurt intake was associated with a reduced risk of hospitalization due to COVID-19. Patients in the third tertiles were about 65% (p for trend = 0.014) and 12% (p for trend = 0.050) less likely to be hospitalized than those in the first tertile, respectively. Dairy consumption, especially low-fat ones, was associated with a lower risk of hospitalization due to COVID-19 and lower severity of COVID-19.

Malnutrition and its association with the mortality in liver cirrhosis; a prospective nutritional assessment in two referral centers in Iran.

INTRODUCTION: Liver cirrhosis is a chronic condition caused by different conditions including viral infection, alcoholism, and autoimmune disorders. Malnutrition is one of the complications of liver cirrhosis that is associated with poor outcomes. This study aimed to determine the association of malnutrition with mortality in liver cirrhosis patients. METHODS: This prospective cross-sectional study was conducted on liver cirrhosis patients who were referred to two referral centers for liver disease in Tehran, Iran. Patients' information including demographics (age, gender, etiology of cirrhosis, alcohol and smoking history) in addition to triceps skinfold (TSF), mid-arm circumference (MAC), Child-Pugh score and Model for End-Stage Liver Disease (MELD) score were recorded in all patients. Patients were classified into A, B, and C categories based on the Subjective Global Assessment (SGA) questionnaire. RESULTS: Among 121 participants (68.6%) were males and the mean age was 54.78. Viral infections were the most common etiology and 65 patients (56.2%) were in the classification A of Child-Pugh Score. TSF (P = 0.001) and MAC (P = 0.003) were significantly lower in SGA class C. The survival rate in SGA class C was significantly lower than other groups (P < 0.001; log-rank test). The risk of mortality in patients with SGA class A and B was 85% (HR value: 0.15; 95% CI: 0.02-0.87; P = 0.03) and 76% (HR value: 0.24; 95% CI: 0.06-0.83; P = 0.02) lower than those with SGA class C. CONCLUSION: Anthropometric and SGA measure are two easy and accessible methods for assessing malnutrition and mortality in liver cirrhosis patients.

Plant-based diet and COVID-19 severity: results from a cross-sectional study.

Although previous findings have shown the beneficial role of healthy eating pattern on the human immune system, the association between plant-based diet and COVID-19 severity has not yet been elucidated. This study aimed to determine the possible role of plant-based diet index (PDI) in COVID-19 severity. This cross-sectional, multicentral study was conducted on 141 patients with confirmed COVID-19. Dietary intakes of the patients were evaluated using a validated food frequency questionnaire. Then, PDI was compared between patients who needed to be hospitalised (considered severe cases), and those who got treatment at home (considered non-severe cases). After adjustment for confounders including age, sex, energy intake and body mass index, lower odds of hospitalisation were found for participants having a greater score of overall PDI (OR per 10 units increase: 0.42; 95% CI 0.22 to 0.80) and healthy PDI (OR per 10 unit increase: 0.45; 95% CI 0.26 to 0.78). In conclusion, our data presented that there is a relation between PDI and lower risk of hospitalisation in COVID-19 patients, possibly through boosting the immune function.

Differential Effects of the Lateral Hypothalamus Lesion as an Origin of Orexin and Blockade of Orexin-1 Receptor in the Orbitofrontal Cortex and Anterior Cingulate Cortex on Their Neuronal Activity.

Introduction: Introduction: Several studies have demonstrated that orexins may regulate different forms of affective and cognitive processes during wakefulness. The Orbitofrontal Cortex (OFC) and Anterior Cingulate Cortex (ACC), as an essential part of the Prefrontal Cortex (PFC), have a crucial role in cognitive processes such as reward and decision-making. They also have a high amount of orexin receptor type 1 (OX1Rs). Methods: In the present study, we inhibited OX1Rs in this area after a 10-min baseline recording to find out the role of OX1Rs in the OFC neuron's firing rate. Next, we inhibited the lateral hypothalamus (LH) as the primary source of orexinergic neurons. Afterward, using a single-unit recording technique in rats, we detected the effects of the lateral hypothalamus on the firing rate and activity pattern of the ACC or OFC neurons. Results: Data showed that the blockade of OX1Rs in the OFC could excite 8 and inhibit 1 neuron(s) out of 11. In addition, the blockade of OX1Rs in the ACC could excite 6 and inhibit 3 neurons out of 10. LH inactivation excited 5 out of 12 neurons and inhibited 6 in the ACC. It also excited 8 and inhibited 6 neurons out of 14 in the OFC. These data suggest that the blockade of OX1Rs excites 72% of the neurons, but LH inactivation had a stimulating effect on only 50% of neurons in two main subregions of the PFC. Conclusion: Accordingly, PFC neurons may receive the orexinergic inputs from the LH and indirectly from other sources. Highlights: Blockade of orexin receptors 1 in ACC alter neural activity in this region.Blockade of orexin receptors 1 in OFC alter neural activity in this region.Lateral hypothalamus inhibition increase neural activity of only 50% neurons in ACC and OFC. Plain Language Summary: The discovery of the neuropeptide orexin/hypocretin in 1998 and subsequent research during the past 20 years revealed an important role for the lateral hypothalamus (LH) in driving the reward pathway, sleep and awake circuits, decision making and psychotic disorders. But our knowledge towards the function of this neurotransmitter on neural activity in specific areas of the brain is limited. In this study we decided to clear the specific role of orexin receptors placed in the two crucial areas of medial prefrontal cortex (mPFC) and the orexin projections from LH on neural firing rates in those regions. In the present study, we investigated the following items by using an in vivo extracellular single-unit recording technique in rats and our data shown that the effect of blocking of orexin receptors1 in mPFC caused a different results than inhibition of the origin of orexin projection in LH as a source of it.

The effect of low FODMAP diet with and without gluten on irritable bowel syndrome: A double blind, placebo controlled randomized clinical trial.

BACKGROUND & AIM: Although the effects of low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet on amelioration of irritable bowel syndrome (IBS) symptoms have been reported previously, it has not yet been elucidated whether the gluten of wheat and barley induces the symptoms or only their fructans lead to aggravation of the symptoms. The aim of this study was to assess the effect of low FODMAPs diet with vs. without gluten on clinical symptoms in IBS patients. METHODS: In this double-blind, placebo-controlled randomized trial, forty nine IBS patients were randomly assigned to placebo and/or intervention group. Patients in the intervention group received 5 gr/day of gluten powder with low FODMAP diet, while placebo group received 5 gr of rice flour as placebo, with low FODMAP diet. Quality of life (QoL) and IBS-SSS (symptom severity score) were measured before and after the intervention using a valid QoL questionnaire and a standard visual analog scale, respectively. RESULTS: Significant improvements were observed in total scores of IBS-SSS (-32% vs. - 49%), abdominal pain intensity (-45% vs. -52%), and frequency (-26 vs. -46%), abdominal distension (-29% vs. -63%), Interference with community function (-14% vs. -45%) and quality of life (+23 vs. +32%) in both gluten and placebo groups respectively (P < 0.05). Only 5 patients in the gluten-containing diet reported exacerbation of their symptoms. CONCLUSION: Exacerbation of IBS symptoms after wheat and barley consumption is due to their fructan, and not related to their gluten content in most of the patients. CLINICAL TRIAL REGISTRATION NO: IRCT20100524004010N29.

Evaluating macro- and micronutrients and food groups intake with the risk of developing inflammatory bowel disease: Is there any association?

Growing clinical evidence represented that certain dietary components are involved in inflammatory bowel disease (IBD) development and progression. This research, therefore, aimed to evaluate whether there exists any relationship between nutrients and IBD. This case-control study from 2017 to 2019 was performed on 145 newly diagnosed IBD patients and 145 BMI-, sex-, and age-matched healthy controls who were recruited from a hospital clinic. A validated 168-item food frequency questionnaire was completed by each participant. Anthropometric measurements and physical activity levels were measured for all participants. Stata software was used to analyze all data. Of the 234 study individuals who participated, 112 were IBD patients and 122 were healthy people. The higher amount of seafood and cholesterol was related to an increased risk of IBD and ulcerative colitis development; however, individuals who had a higher intake of calcium were less likely to have Crohn's compared to the healthy group. There was a positive relation between honey and jam, seafood, organ meats, salt, fruits on trees, fruit juice, olives, and nuts and the probability of IBD, but there was a negative association between refined grains, potatoes, salty snacks, legumes, dairy, and cruciferous and the probability of IBD. Higher consumption of seafood and cholesterol was positively connected with a higher risk of IBD development in the current case-control study. A substantial association was seen between honey and jam, seafood, organmeats, salt, fruit on trees, fruit juice, olives, and nut consumption and IBD developement.