Fibroblast cell-based therapy prevents induction of alopecia areata in an experimental model

YesAlopecia areata (AA) is an autoimmune hair loss disease with infiltration of proinflammatory cells into hair follicles. Current therapeutic regimens are unsatisfactory mainly because of the potential for side effects and/or limited efficacy. Here we report that cultured, transduced fibroblasts, which express the immunomodulatory molecule indoleamine 2,3-dioxygenase (IDO), can be applied to prevent hair loss in an experimental AA model. A single intraperitoneal (IP) injection of IDO-expressing primary dermal fibroblasts was given to C3H/HeJ mice at the time of AA induction. While 60–70% of mice that received either control fibroblasts or vehicle injections developed extensive AA, none of the IDO-expressing fibroblast-treated mice showed new hair loss up to 20 weeks post injection. IDO cell therapy significantly reduced infiltration of CD4+ and CD8+ T cells into hair follicles and resulted in decreased expression of TNF-α, IFN-γ and IL-17 in the skin. Skin draining lymph nodes of IDO fibroblast-treated mice were significantly smaller, with more CD4+ CD25+ FoxP3+ regulatory T cells and fewer Th17 cells than those of control fibroblast and vehicle-injected mice. These findings indicate that IP injected IDO-expressing dermal fibroblasts can control inflammation and thereby prevent AA hair loss.Canadian Institutes of Health Researches (Funding Reference Number: 134214 and 136945)

Vitamin D binding protein gene polymorphisms and risk of type 1 diabetes mellitus among Egyptians

Type 1 diabetes (T1DM) is a multifactorial autoimmune disease in which both genetic predisposition and environmental factors participate in its development. Many cellular and epidemiological studies suggest a role for vitamin D in pathogenesis and prevention of T1DM. Polymorphisms of the genes involved in the metabolism of vitamin D may predispose to T1DM. Vitamin D-binding protein (DBP) is the main systemic transporter of vitamin D and is essential for its cellular endocytosis. There are two known polymorphisms in exon 11 of the DBP gene resulting in amino acid variants: GAT→GAG substitution replaces aspartic acid by glutamic acid in codon 416; and ACG→AAG substitution in codon 420 leads to an exchange of threonine for lysine. These DBP variants lead to differences in the affinity for vitamin D. Few published studies, about the correlation between these alleles and T1DM, yielded conflicting results. Therefore, we investigated the association of these polymorphisms with T1DM in Egyptian subjects. Unrelated 59 children with T1DM and 65 healthy controls were included in this study. The sequence of DBP exon 11, which contains both examined variants, was amplified by polymerase chain reaction (PCR). Alleles and genotypes were determined using Restriction Fragment Length Polymorphism analysis (RFLP). At codon 416 the frequency of Glu/Asp alleles was 64.4/35.6% in T1DM patients and 55.4/44.6% in controls (P >0.05). At codon 420 the frequency of Thr/Lys alleles were 88.1/11.9% and 87.7/12.3% (P >0.05), respectively. Distributions of genotypes at both loci, and the common haplotypes constructed by them, were also very similar in both groups (P >0.05). It could be concluded that the studied DNA polymorphisms in the DBP gene are not associated with T1DM in Egyptian patients.Key words: Type 1 diabetes Mellitus (T1DM), Vitamin D binding protein (DBP), polymorphis

Nutritional Quality Assessment of Miscellaneous Cassava Tubers Using Principal Component Analysis and Cluster Analysis

Cassava is a staple crop in developing countries because its starchy roots provide essential dietary carbohydrates. The aim of this research was to conduct a comprehensive inquiry and scientific evaluation of the nutritional value of cassava tubers. Eight nutritional characteristics were examined in native and imported cassava variants: starch, reduced sugar, anthocyanins, protein, dietary fiber, quinic acid, vitamin C, and dry matter content. Principal component analysis (PCA) was conducted to minimize the dimensionality of the nutritional markers. A scientific assessment technique was developed to calculate a composite score for the various cassava samples. Analysis of the data revealed noticeable variance among the samples’ nutritional indicators, suggesting varying degrees of association. Starch had a substantial positive link with lower sugar, protein, and dry matter content (p p p p < 0.05). The contribution rate of the top three PCA factors was over 76%, demonstrating that these factors incorporated the primary information acquired from the eight original nutritional indices, while maintaining excellent representativeness and impartiality. The experimental results showed a preliminary nutritional grade for 22 cassava tuber samples. The top five types were Guangxi Muci, Gui Cassava 4, Glutinous Rice Cassava, Huifeng 60, and Dongguan Hongwei. In the cluster analysis, the levels of similarity between the data showed that the 22 types of cassava tubers could be grouped into five categories, each with their own set of nutrients. This study promotes the directed breeding of cassava species and offers a theoretical foundation for creating and using various cassava varieties. Furthermore, this work lays the groundwork for a systematic and dependable technique for the quality assessment, comprehensive evaluation, and reasonable classification of cassava species and similar crops

Attenuation of inflammation, oxidative stress and TGF-β1/Smad3 signaling and upregulation of Nrf2/HO-1 signaling mediate the protective effect of diallyl disulfide against cadmium nephrotoxicity

Heavy metals are toxic environmental pollutants with serious health effects on humans and animals. Cadmium (Cd) is known for its serious nephrotoxic effect and its toxicity involves oxidative stress (OS) and inflammation. Diallyl disulfide (DADS), a main constituent of garlic, exhibites cytoprotective and antioxidant activities. This study investigated the effect of DADS on OS, inflammation, and fibrosis induced by Cd in rat kidney, pointing to the involvement of transforming growth factor-β (TGF-β)/Smad3 and nuclear factor erythroid 2–related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling, and peroxisome proliferator-activated receptor gamma (PPARγ). Rats received DADS for 14 days and Cd on day 7 and blood and kidney samples were collected. Cd elevated serum creatinine, urea and uric acid, provoked kidney histopathological alterations and collagen deposition, increased kidney malondialdehyde (MDA) level, and decreased glutathione (GSH) and antioxidant enzymes. Nuclear factor-kappaB (NF-κB) p65, interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1β, and CD68 were upregulated in Cd-administered rat kidney. DADS prevented kidney injury, mitigated OS, suppressed NF-κB, CD68 and pro-inflammatory mediators, and boosted antioxidants. DADS downregulated TGF-β1, Smad3 phosphorylation and Kelch-like ECH-associated protein-1 (Keap1), and increased Nrf2, HO-1, cytoglobin, and PPARγ. In conclusion, DADS protects the kidney against Cd toxicity by attenuating OS, inflammation, and TGF-β1/Smad3 signaling, and enhancement of Nrf2/HO-1 signaling, antioxidants, and PPARγ

The Effect of Hydrostatic Initial Stress on the Plane Waves in a Fiber-Reinforced Magneto-Thermoelastic Medium with Fractional Derivative Heat Transfer

An effect of three factors - the order of fractional derivative, the hydrostatic initial stress, and parameter of magnetic field – on the plane waves in the half-space made of fiber-reinforced material, that is described by the theory of generalized magnetothermoelasticity, is studied. The problem is solved numerically using the normal mode analysis. The results correspond to the Lord-Shulman model and the model, that uses the fractional derivatives and are presented in the form of graphs. The findings show pronounced effect of mentioned three factors. The results are compared with the case, when the initial stress and magnetic field are absent.Вивчено вплив трьох факторів – порядку дробових похідних, початкового гідростатичного напруження, параметру магнітного поля – на плоскі хвилі в півпросторі з армованого волокнами матеріалу, який описується теорією узагальненої магнітотермопружності. Задача розв’язана чисельно за допомогою аналізу нормальних мод. Результати аналізу відповідають моделі Лорда – Шульмана і моделі, що описується за допомогою дробових похідних, і представлені у вигляді графіків. Отримані результати показують добре виражений вплив вказаних трьох факторів. Також ці результати порівнюються з результатами, що отримані для випадку відсутності початкового гідростатичного напруження і магнітного поля