Intestinal tolerance requires gut homing and expansion of FoxP3+ regulatory T cells in the lamina propria

Tolerance to food antigen manifests in the absence and/or suppression of antigen-specific immune responses locally in the gut but also systemically, a phenomenon known as oral tolerance. Oral tolerance is thought to originate in the gut-draining lymph nodes, which support the generation of FoxP3(+) regulatory T (Treg) cells. Here we use several mouse models to show that Treg cells, after their generation in lymph nodes, need to home to the gut to undergo local expansion to install oral tolerance. Proliferation of Treg cells in the intestine and production of interleukin-10 by gut-resident macrophages was blunted in mice deficient in the chemokine (C-X3-C motif) receptor 1 (CX3CR1). We propose a model of stepwise oral tolerance induction comprising the generation of Treg cells in the gut-draining lymph nodes, followed by migration into the gut and subsequent expansion of Treg cells driven by intestinal macrophages.     

The ameliorative effects of methylene blue on testicular damage induced by cisplatin in rats

Cisplatin, a common chemotherapeutic drug, can induce testicular toxicity. Methylene blue, a potent antioxidant, can inhibit the generation of free radicals. This research aimed to study the protective effect of methylene blue against the cisplatin-induced toxicity of the reproductive system in rats. 35 male Wistar rats were divided into five groups: the control group, the cisplatin group (a single dose of 5 mg/kg cisplatin), the low-dose and high-dose methylene blue + cisplatin (2 and 4 mg/kg of methylene blue, respectively, for 7 days) and the methylene blue group (4 mg/kg of methylene blue, for 7 days). The treatments were applied through intraperitoneal injection. Cisplatin treatment reduced the sperm parameters and serum testosterone levels significantly. Methylene blue treatment increased the sperm count (p < .001), viability (p < .001) and motility (p < .001) compared to the cisplatin group. The methylene blue group showed a significant increase in the levels of testosterone compared to the cisplatin group (p < .001) and reverted histopathological changes in cisplatin-treated groups. Immunohistochemical evaluation of the caspase-3 protein revealed that the treatment with methylene blue has significant anti-apoptotic effects on testicular tissue damage. In conclusion, methylene blue can attenuate the cisplatin-induced histological damages and improve the sperm parameters.     

Photobiomodulation of oral fibroblasts stimulated with periodontal pathogens

Lasers in Medical Science - Photobiomodulation (PBM) utilises light energy to treat oral disease, periodontitis. However, there remains inconsistency in the reporting of treatment parameters and a...     

Functional Promoter Polymorphisms of MMP-2 C-735T and MMP-9 C-1562T and Their Synergism with MMP-7 A-181G in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system. Matrix metalloproteinases (MMPs) play an important role in breakdown of blood–brain barrier, transmigration, and invasion of immune cells and formation of MS lesions. The aim of present study was to investigate the influence of MMP-2 C-735T and MMP-9 C-1562T variants and their synergism with MMP-7 A-181G on susceptibility to MS. In a case–control study 125 MS patients and 235 healthy individuals from Western Iran were investigated. The various genotypes of MMP-2, MMP-9, and MMP-7 were detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In females the presence of MMP-2 C allele was associated with an increased risk of MS (OR = 1.69, p = 0.041). No significant difference was detected between the frequency of MMP-9 T allele in MS patients (8.2%) and controls (12.8%, p = 0.068). The concomitant presence of both MMP-2 C and MMP-7 G alleles was associated with 1.82-fold increased risk of MS (p = 0.002). Also, a synergism was detected between MMP-9 C and MMP-7 G alleles that elevated the risk of MS by 1.5-times (p = 0.035). The presence of haplotype MMP-9 T, MMP-7 G, and MMP-2 C (TGC) compared to haplotype CAG increased the risk of MS by 3.13-fold (p = 0.16). The present study suggests that gene–gene interactions and variants of more genes instead of single gene might play a role in susceptibility to MS. We indicated that synergism between variants of MMP-2, MMP-7, and MMP-9 genes might increase the risk of MS.     

Omega-3 fatty acids’ effect on leptin and adiponectin concentrations in patients with spinal cord injury: A double-blinded randomized clinical trial

Context

Omega-3 fatty acids have been recently proposed to induce neural improvement in patients with spinal cord injury (SCI) while affecting some hormones including leptin and adiponectin.

Objectives

We tried to evaluate the effect of omega-3 fatty acids on circulatory concentrations of leptin and adiponectin among these patients.

Design

This study is a double-blinded randomized clinical trial with intervention duration of 14 months.

Setting

A tertiary rehabilitation center.

Participants

Total of 104 patients with SCI who did not meet our exclusion criteria entered the study. Those with history of diabetes, cancer, endocrinology disease, acute infection, and use of special medications were excluded. Patients were divided randomly into the treatment and control group by using permuted balanced block randomization.

Intervention

The treatment group received two MorDHA^® capsules per day (each capsule contain 465 mg of docosahexaenoic acid (DHA) and 63 mg of eicosapentaenoic acid (EPA)) for 14 months while the control group received placebo capsules with similar color, shape, and taste.

Main outcomes measures

Leptin and adiponectin concentrations in plasma were measured at the beginning of trial and then after 6 and 14 months.

Results

Fourteen months of treatment with DHA and EPA did not influence concentrations of leptin but adiponectin level was significantly decreased (P: 0.03). Weight was positively correlated with leptin level at stage 0 of trial (P: 0.008, r = 0.41) while this association was attenuated through stages of trial after intervention.

Conclusion

Our data show that omega-3 fatty acids may not affect plasma concentrations of leptin but adiponectin level is decreased in patients with SCI. Moreover, this intervention influences the linear relationship between weight and leptin after 14 months administration of DHA and EPA.     

Potato Consumption and Risk of Site-Specific Cancers in Adults: A Systematic Review and Dose-Response Meta-Analysis of Observational Studies

The etiology of cancer type may vary significantly due to anatomy, embryology, and physiology of the cancer site. Although the association between potato consumption and colorectal cancer (CRC) was summarized in a 2018 meta-analysis of 5 cohort studies, to the best of our knowledge, no meta-analysis has evaluated potato consumption in relation to multiple cancer sites in adults. Medline/PubMed, ISI Web of Knowledge, Scopus, and the Cochrane Database of Systematic Reviews were searched for relevant publications through August 2020. We selected cohort or case-control studies conducted in adults that reported risk estimates (relative risk [RRs], HRs, and ORs) of potato intake for any cancer type. Random effects meta-analyses compared high and low intake categories. Twenty prospective cohort studies (total n = 785,348) including 19,882 incident cases, and 36 case-control studies (21,822 cases; 66,502 controls) were included. Among cohort studies, we did not find an association between high versus low intake of total potato (white and yellow) consumption and overall cancers: 1.04 (95% CI: 0.96, 1.11; tau² = 0.005, n = 18). We found no relation between total potato consumption (high compared with low intake) and risk of CRC, pancreatic cancer, colon, gastric, breast, prostate, kidney, lung, or bladder cancer in cohort or case-control studies. We did not find an association between high versus low consumption of potato preparations (boiled/fried/mashed/roasted/baked) and risk of gastrointestinal-, sex-hormone-, or urinary-related cancers in cohort or case-control studies. Certainty of the evidence was low for total cancer, CRC, colon, rectal, renal, pancreatic, breast, prostate, and lung cancer and very low for gastric and bladder cancer. In conclusion, potato intake or potato preparations were not associated with multiple cancer sites when comparing high and low intake categories. This finding was consistent with the findings from the 2018 meta-analysis regarding potato intake and risk of CRC.     

Evaluation of backbone-cyclized HER2-binding 2-helix Affibody molecule for In Vivo molecular imaging

IntroductionAffibody molecules, small scaffold proteins, have demonstrated an appreciable potential as imaging probes. Affibody molecules are composed of three alpha-helices. Helices 1 and 2 are involved in molecular recognition, while helix 3 provides stability. The size of Affibody molecules can be reduced by omitting the third alpha-helix and cross-linking the two remaining, providing a smaller molecule with better extravasation and quicker clearance of unbound tracer. The goal of this study was to develop a novel 2-helix Affibody molecule based on backbone cyclization by native chemical ligation (NCL).MethodsThe HER2-targeting NCL-cyclized Affibody molecule Z_HER2:342min has been designed, synthesized and site-specifically conjugated with a DOTA chelator. DOTA-Z_HER2:342min was labeled with ¹¹¹In and ⁶⁸ Ga. The binding affinity of DOTA-Z_HER2:342min was evaluated in vitro. The targeting properties of ¹¹¹In- and ⁶⁸ Ga-DOTA-Z_HER2:342min were evaluated in mice bearing SKOV-3 xenografts and compared with the properties of ¹¹¹In- and ⁶⁸ Ga-labeled PEP09239, a DOTA-conjugated 2-helix Affibody analogue cyclized by a homocysteine disulfide bridge.ResultsThe dissociation constant (K_D) for DOTA-Z_HER2:342min binding to HER2 was 18 nM according to SPR measurements. DOTA-Z_HER2:342min was labeled with ¹¹¹In and ⁶⁸ Ga. Both conjugates demonstrated bi-phasic binding kinetics to HER2-expressing cells, with K_D1 in low nanomolar range. Both variants demonstrated specific uptake in HER2-expressing xenografts. Tumor-to-blood ratios at 2 h p.i. were 6.1 ± 1.3 for ¹¹¹In- DOTA-Z_HER2:342min and 4.6 ± 0.7 for ⁶⁸ Ga-DOTA-Z_HER2:342min. However, the uptake of DOTA-Z_HER2:342min in lung, liver and spleen was appreciably higher than the uptake of PEP09239-based counterparts.ConclusionsNative chemical ligation enables production of a backbone-cyclized HER2-binding 2-helix Affibody molecule (Z_HER2:342min) with low nanomolar target affinity and specific tumor uptake.     

Calorie and macronutrients intake in people with spinal cord injuries: an analysis by sex and injury-related variables

ObjectiveCurrent studies suggest that two of every three persons with spinal cord injury are at risk for the metabolic consequences of obesity. The objective of this study was to assess the dietary intakes in people with spinal cord injury based on sex- and injury-related variables.MethodsIn total 162 people with spinal cord injury participated in this cross-sectional study. Their dietary intakes were assessed by a semiquantitative food-frequency questionnaire.ResultsThe percentages of total energy intake derived from macronutrients were 53% carbohydrate, 10% protein, and 37% fat for men and 52% carbohydrate, 11% protein, and 39% fat for women. There was excessive consumption of simple carbohydrates (102.17 ± 40.83). The participants with longer times since injury had lower cholesterol intakes (P = 0.02). The individuals with an incomplete injury consumed significantly more monounsaturated fatty acids (n = 114, 27.2 ± 12.01 g) than those with a complete injury (n = 48, 23.6 ± 8.08 g, P = 0.03). There was a significant positive correlation of age and time since injury with fiber intake (P < 0.05).ConclusionThe balance of macronutrients shifted toward intakes of fat and simple carbohydrates at the expense of complex carbohydrates, fiber, and protein in these participants. Mean amounts of polyunsaturated and monounsaturated fatty acids in these participants were above the recommended intakes. Older participants and those with a longer time since injury tended to have lower calorie, fat, carbohydrate, saturated fat, and cholesterol intakes and higher fiber intakes.