Pre- and post-estrogen administration in global cerebral ischemia reduces blood-brain barrier breakdown in ovariectomized rats

The aim of present study was to determine the effect of estrogen treatment on blood-brain barrier permeability in rats with induced global cerebral ischemia. The study included six-month-old female Sprague-Dawley rats which were divided into the following groups: Control-Ischemia-Reperfusion (C + I-R); Ovariectomy-Ischemia-Reperfusion (Ovx + I-R); Ovariectomy + Estrogen + Ischemia-Reperfusion (Ovx + E + I-R); Ovariectomy + Ischemia-Reperfusion + Estrogen (Ovx + I-R + E). Ischemia-reperfusion was induced by clamping two carotid arteries, then opening the clamp. Blood-brain barrier permeability was visualized by Evans Blue extravasation and quantified by spectrophotometry. Our results indicate that following ischemia-reperfusion the BBB permeability is increased in ovariectomized rats (Evans Blue extravasation) compared to the control group in the cortex, thalamus, hippocampus, cerebellum and brain stem, while in the midbrain no significant increase was detected. In contrast, BBB permeability in the groups treated with estrogen, administered either before or after ischemia-reperfusion, was significantly lower than in ovariectomized animals. In conclusion, the increase in BBB permeability resulting from experimentally induced cerebral ischemia was prevented by exogenous estrogen treatment. The study results indicate that estrogen may be used for therapeutic purposes in ischemia-reperfusion

Padres Preparados, Jóvenes Saludables: intervention impact of a randomized controlled trial on Latino father and adolescent energy balance-related behaviors

Studies have shown associations among food and activity behaviors and body weight of Latino fathers and adolescents. However, few Latino father-focused interventions have been designed to improve energy balance-related behaviors (EBRBs) and weight status among early adolescents. Thus, this efficacy study aims to evaluate the Padres Preparados, Jóvenes Saludables (Padres) youth obesity prevention program for positive changes in EBRBs (fruit, vegetable, sugar-sweetened beverage (SSB), sweet/salty snack, and fast-food consumption, physical activity, and screen time) and weight status among low-income Latino fathers and adolescents (10-14 years). A two-arm (treatment versus delayed-treatment control group) randomized controlled trial was conducted to evaluate the efficacy of 8 weekly experiential learning sessions (2.5 hours each) based on social cognitive theory. The sessions included food preparation, parenting skills, nutrition, and physical activity. The program was delivered to father-adolescent dyads (mothers were encouraged to attend) in trusted community-based settings in a Midwest metropolitan area between 2017 and 2019. In March 2020, in-person implementation was discontinued due to COVID-19 pandemic restrictions, which limited the sample size. Father/adolescent dyads were randomized to treatment or control group within each site. Surveys and measurements were completed by fathers and adolescents to assess changes in food and activity behaviors from baseline to post-intervention. Adolescents also completed 24-hour dietary recall interviews at baseline and post-intervention. Intervention effects were assessed using linear regression mixed models adjusted for covariates and accounting for clustering of participants within sites. Data from 147 father/adolescent dyads who completed at least the baseline data collection were used. No significant differences were observed for baseline to post-intervention changes in adolescents’ and fathers’ EBRBs or weight status between treatment and control groups. Fathers’ SSB and fast food intakes were not statistically significant (p = 0.067 and p = 0.090, respectively). The Padres program resulted in no significant improvements in adolescent and father EBRBs and weight status. Additional Latino father-focused interventions are needed to examine intervention effects on EBRBs among Latino adolescents.https://doi.org/10.1186/s12889-022-14284-

A Nutrigenetic approach to examine the relationship between vitamin B12 status and cardio-metabolic traits in multiple ethnic groups – findings from the GeNuIne Collaboration

Low vitamin B12 concentrations have been shown to be risk factors for metabolic traits in numerous observational studies; however, the relationship has remained inconsistent. It is possible that certain genotypes jointly contribute to obesity and vitamin B12 deficiency, and these may be modulated by dietary factors. The main objective of this review article was to summarize the effect of gene-nutrient interactions on vitamin B12 concentrations and cardio-metabolic disease risk factors using population-based studies from different ethnic groups from the GeNuIne (Gene-Nutrient Interactions) Collaboration. Interactions between vitamin B12-related SNPs and protein energy intake (%) on waist circumference (Pinteration=0.002) and body fat percentage (Pinteraction=0.034), were observed in Sri Lankan and Indonesian populations, respectively. In the study in Brazilian adolescents, the metabolic and vitamin B12 related SNPs showed a significant interaction with carbohydrate and protein intakes on oxidised low density lipoprotein cholesterol and homocysteine concentrations, respectively. In the Asian Indian population, an association between obesity-related SNPs and vitamin B12 concentrations (P = 0.018) was observed. In summary, these studies in multiple ethnic groups show that the association between genetically low vitamin B12 concentrations and metabolic outcomes may be modified by dietary intake. Further studies utilising larger sample sizes are needed to confirm or refute our findings

Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants

Gamma-aminobutyric acid (GABA) and glutamate are the most abundant amino acid neurotransmitters in the brain. GABA, an inhibitory neurotransmitter, is synthesized by glutamic acid decarboxylase (GAD). Its predominant isoform GAD67, contributes up to ∼90% of base-level GABA in the CNS, and is encoded by the GAD1 gene. Disruption of GAD1 results in an imbalance of inhibitory and excitatory neurotransmitters, and as Gad1−/− mice die neonatally of severe cleft palate, it has not been possible to determine any potential neurological dysfunction. Furthermore, little is known about the consequence of GAD1 disruption in humans. Here we present six affected individuals from six unrelated families, carrying bi-allelic GAD1 variants, presenting with developmental and epileptic encephalopathy, characterized by early-infantile onset epilepsy and hypotonia with additional variable non-CNS manifestations such as skeletal abnormalities, dysmorphic features and cleft palate. Our findings highlight an important role for GAD1 in seizure induction, neuronal and extraneuronal development, and introduce GAD1 as a new gene associated with developmental and epileptic encephalopathy

Effects of dietary supplementation of nickel and nickel-zinc on femoral bone structure in rabbits

<p>Abstract</p> <p>Background</p> <p>Nickel (Ni) and zinc (Zn) are trace elements present at low concentrations in agroecosystems. Nickel, however, may have toxic effects on living organisms and is often considered as a contaminant. This study reports the effect of peroral administrated Ni or a combination of Ni and Zn on femoral bone structure in rabbits.</p> <p>Methods</p> <p>One month-old female rabbits were divided into three groups of five animals each. Group 1 rabbits were fed a granular feed mixture with addition of 35 g NiCl₂per 100 kg of mixture for 90 days. In group 2, animals were fed a mixture containing 35 g NiCl₂and 30 g ZnCl₂per 100 kg of mixture. Group 3 without administration of additional Ni or Zn served as control. After the 90-day experimental period, femoral length, femoral weight and histological structure of the femur were analyzed and compared.</p> <p>Results</p> <p>The results did not indicate a statistically significant difference in either femoral length or weight between the two experimental groups and the control group. Also, differences in qualitative histological characteristics of the femora among rabbits from the three groups were absent, except for a fewer number of secondary osteons found in the animals of groups 1 and 2. However, values for vascular canal parameters of primary osteons were significantly lower in group 1 than in the control one. Peroral administration of a combination of Ni and Zn (group 2) led to a significant decreased size of the secondary osteons.</p> <p>Conclusions</p> <p>The study indicates that dietary supplementation of Ni (35 g NiCl₂per 100 kg of feed mixture) and Ni-Zn combination (35 g NiCl₂and 30 g ZnCl₂per 100 kg of the mixture) affects the microstructure of compact bone tissue in young rabbits.</p

Bio-Based Succinate Production from Arundo donax Hydrolysate with the New Natural Succinic Acid-Producing Strain Basfia succiniciproducens BPP7

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Alteration of proliferation and apoptotic markers in normal and premalignant tissue associated with prostate cancer

BACKGROUND: Molecular markers identifying alterations in proliferation and apoptotic pathways could be particularly important in characterizing high-risk normal or pre-neoplastic tissue. We evaluated the following markers: Ki67, Minichromosome Maintenance Protein-2 (Mcm-2), activated caspase-3 (a-casp3) and Bcl-2 to determine if they showed differential expression across progressive degrees of intraepithelial neoplasia and cancer in the prostate. To identify field effects, we also evaluated whether high-risk expression patterns in normal tissue were more common in prostates containing cancer compared to those without cancer (supernormal), and in histologically normal glands adjacent to a cancer focus as opposed to equivalent glands that were more distant. METHODS: The aforementioned markers were studied in 13 radical prostatectomy (RP) and 6 cystoprostatectomy (CP) specimens. Tissue compartments representing normal, low grade prostatic intraepithelial neoplasia (LGPIN), high grade prostatic intraepithelial neoplasia (HGPIN), as well as different grades of cancer were mapped on H&E slides and adjacent sections were analyzed using immunohistochemistry. Normal glands within 1 mm distance of a tumor focus and glands beyond 5 mm were considered "near" and "far", respectively. Randomly selected nuclei and 40 × fields were scored by a single observer; basal and luminal epithelial layers were scored separately. RESULTS: Both Ki-67 and Mcm-2 showed an upward trend from normal tissue through HGPIN and cancer with a shift in proliferation from basal to luminal compartment. Activated caspase-3 showed a significant decrease in HGPIN and cancer compartments. Supernormal glands had significantly lower proliferation indices and higher a-casp3 expression compared to normal glands. "Near" normal glands had higher Mcm-2 indices compared to "far" glands; however, they also had higher a-casp3 expression. Bcl-2, which varied minimally in normal tissue, did not show any trend across compartments or evidence for field effects. CONCLUSION: These results demonstrate that proliferation and apoptosis are altered not only in preneoplastic lesions but also in apparently normal looking epithelium associated with cancer. Luminal cell expression of Mcm-2 appears to be particularly promising as a marker of high-risk normal epithelium. The role of apoptotic markers such as activated caspase-3 is more complex, and might depend on the proliferation status of the tissue in question

Metallothionein – overexpression as a highly significant prognostic factor in melanoma: a prospective study on 1270 patients

Metallothioneins (MT) are ubiquitous, intracellular small proteins with high affinity for heavy metal ions. In the last decades, it was shown that MT overexpression in a variety of cancers is associated with resistance to anticancer drugs and is combined with a poor prognosis. In this prospective study, we examined the role of MT overexpression in melanoma patients as a prognostic factor for progression and survival. Between 1993 and 2004, 3386 patients with primary cutaneous melanoma were investigated by using a monoclonal antibody against MT on routinely fixed, paraffin-embedded tissues. In all, 1270 patients could be followed up for further statistical analysis (Fisher's exact test, Mantel–Haenszel χ2 test, Kaplan–Meier curves). The MT data of disease-free interval and overall survival were compared univariately and multivariately in Cox regression analysis. Immunohistochemical overexpression of MT in tumour cells of patients with primary melanoma (310 of 1270; 24.4%) was associated with a higher risk for progression (117 of 167; 70.1%) and reduced survival (80 of 110; 72.7%) of the disease (P<0.0001). Similarly, Kaplan–Meier curves gave highly significant disadvantages for the MT-positive group. Univariate analysis (relative risk 7.4; 95% confidence interval (CI) 5.2–10.2; P<0.0001 for progression; relative risk 7.1; 95% CI 4.7–10.9; P<0.0001 for survival), as well as multivariate analysis with other prognostic markers resulted in MT overexpression as a highly significant and independent factor for prognosis in primary melanoma