Fibroblast state switching orchestrates dermal maturation and wound healing

Murine dermis contains functionally and spatially distinct fibroblast lineages that cease to proliferate in early postnatal life. Here, we propose a model in which a negative feedback loop between extracellular matrix (ECM) deposition and fibroblast proliferation determines dermal architecture. Virtual‐tissue simulations of our model faithfully recapitulate dermal maturation, predicting a loss of spatial segregation of fibroblast lineages and dictating that fibroblast migration is only required for wound healing. To test this, we performed in vivo live imaging of dermal fibroblasts, which revealed that homeostatic tissue architecture is achieved without active cell migration. In contrast, both fibroblast proliferation and migration are key determinants of tissue repair following wounding. The results show that tissue‐scale coordination is driven by the interdependence of cell proliferation and ECM deposition, paving the way for identifying new therapeutic strategies to enhance skin regeneration.     

Salicylic acid changes morpho-physiological attributes of feverfew (Tanacetum parthenium L.) under salinity stress

Feverfew (Tanacetum parthenium) (TP) is a valuable medicinal plant from Asteraceae family with various pharmaceutical and therapeutic properties. A pot experiment was conducted to evaluate the effect of salicylic acid (SA) on the physiological and morphological responses of TP under salinity stress. Salinity was induced by NaCl and CaCl₂ (2:1) at 30, 60, 90, 120, 150 and 180 mM levels. SA was applied as foliar application at 0, 200 and 300 ppm concentrations. Plant height, leaf and shoot number, fresh and dry weight and essential oil, starch, sugar, protein, proline, catalase (CAT), peroxidase (POD), and ascorbic peroxidase (APX) contents were as measured morpho-physiological traits. The results showed that SA significantly (P ≤ 0.05) improved the measured traits and caused higher tolerance in TP plants under salinity stress. The essential oil content increased with increasing the salinity level up to 90 mM, which was more significant when combined with SA application. All of the measured traits except proline content, antioxidant enzymes, essential oil and sugar decreased at high salinity levels.     

RETRACTED ARTICLE: Serum Zinc and Adiponectin Levels in Patients with Polycystic Ovary Syndrome,Adjusted for Anthropometric,Biochemical, Dietary Intake,and Physical Activity Measures

Biological Trace Element Research -     

Enhanced chondrogenic differentiation of dental pulp-derived mesenchymal stem cells in 3D pellet culture system: effect of mimicking hypoxia

High incidence of articular cartilage defects resulting from age-related degeneration or trauma injuries is a major problem worldwide. Limited self-regeneration ability of cartilage often leads to inappropriate biochemistry and structure of healed tissue. Considering Impairments of traditional treatments, cell-based therapies are promising. The rapid ex vivo expansion and chondrogenic differentiation capability make dental pulp stem cells (DPSCs) a favorable cell type for therapeutic application, however strategies in order to efficient cartilage tissue-like production are imperative. In the present study the potential role of hypoxia mimicking agent, cobalt chloride (CoCl2), on chondrogenic differentiation of human DPSCs was surveyed. Cell viability assay used to obtain the optimum dose and exposure time of CoCl2. DPSCs were differentiated in pellet culture system after CoCl2 pretreatment. Chondrogenic differentiation efficiency was evaluated by histological and immunohistological analyses. The results showed that CoCl2 led to increased pellet size, integrity and matrix deposition with organizations more resembled typical cartilage lacuna structure. Furthermore, CoCl2 could improve differentiation by elevated chondrogenic markers, glycosaminoglycans (GAGs) and collagen II expression. CoCl2 pretreatment mitigated hypertrophy, as well, which was reflected in decreased collagen X expression. Alkaline phosphatase (ALP) specific activity did not change significantly by CoCl2 preconditioning. Based on current study hypoxia mimicking agent, CoCl2, could be suggested to promote DPSCs chondrogenic differentiation.     

The Modulatory Effect of Metabotropic Glutamate Receptor Type-1α on Spike-Wave Discharges in WAG/Rij Rats

Modulatory function of metabotropic glutamate type 1 (mGlu1) receptors plays a crucial role in the pathophysiology of some neurological disorders, including schizophrenia and epilepsy. In this study, the expression of mGlu1α receptors in the thalamic nuclei was assessed during development of absence seizures in the WAG/Rij rats, a valid genetic animal model of absence epilepsy. In addition, the effect of pharmacological modulation of mGlu1α receptors in the laterodorsal (LD) nucleus of the thalamus on the characteristic features of bioelectrical brain activities in the WAG/Rij rats was assessed. The expression of mGlu1α receptors in the LD was assessed in four experimental groups of both WAG/Rij and Wistar rats with 2 and 6 months of age. Agonist and antagonist of mGlu1α receptors were infused in LD in the six months old WAG/Rij (epileptic) rats. The protein level of mGlu1α receptors in the thalamus of the 6-month-old WAG/Rij rats was lower than non-epileptic animals. In addition, the distribution of mGlu1α receptors in different thalamic nuclei was lower in the 6-month-old WAG/Rij compared to age-matched Wistar rats. The gene expression of mGlu1α receptor was also significantly lower in 6-month-old WAG/Rij rats in the LD compared to other animal groups. The microinjection of mGlu1α receptors agonist and antagonist in the LD reduced the duration of spike-wave discharges (SWDs) and increased the amplitude and duration of SWDs, respectively, in 6-month-old WAG/Rij rats. The alterations of mGlu1α receptors expression in the thalamus of epileptic WAG/Rij rats as well as its modulatory effects in the generation of SWDs suggest the potential of mGlu1 receptors as a therapeutic target in absence epilepsy.     

The role of caveolae and caveolin 1 in calcium handling in pacing and contraction of mouse intestine

In mouse intestine, caveolae and caveolin‐1 (Cav‐1) are present in smooth muscle (responsible for executing contractions) and in interstitial cells of Cajal (ICC; responsible for pacing contractions). We found that a number of calcium handling/dependent molecules are associated with caveolae, including L‐type Ca²⁺ channels, Na⁺‐Ca²⁺ exchanger type 1 (NCX1), plasma membrane Ca²⁺ pumps and neural nitric oxide synthase (nNOS), and that caveolae are close to the peripheral endo‐sarcoplasmic reticulum (ER‐SR). Also we found that this assemblage may account for recycling of calcium from caveolar domains to SR through L‐type Ca ⁺ channels to sustain pacing and contractions. Here we test this hypothesis further comparing pacing and contractions under various conditions in longitudinal muscle of Cav‐1 knockout mice (lacking caveolae) and in their genetic controls. We used a procedure in which pacing frequencies (indicative of functioning of ICC) and contraction amplitudes (indicative of functioning of smooth muscle) were studied in calcium‐free media with 100 mM ethylene glycol tetra‐acetic acid (EGTA). The absence of caveolae in ICC inhibited the ability of ICC to maintain frequencies of contraction in the calcium‐free medium by reducing recycling of calcium from caveolar plasma membrane to SR when the calcium stores were initially full. This recycling to ICC involved primarily L‐type Ca²⁺ channels; i.e. pacing frequencies were enhanced by opening and inhibited by closing these channels. However, when these stores were depleted by block of the sarco/endoplasmic reticulum Ca²⁺‐ATPase (SERCA) pump or calcium release was activated by carbachol, the absence of Cav‐1 or caveolae had little or no effect. The absence of caveolae had little impact on contraction amplitudes, indicative of recycling of calcium to SR in smooth muscle. However, the absence of caveolae slowed the rate of loss of calcium from SR under some conditions in both ICC and smooth muscle, which may reflect the loss of proximity to store operated Ca channels. We found evidence that these channels were associated with Cav‐1. These changes were all consistent with the hypothesis that a reduction of the extracellular calcium associated with caveolae in ICC of the myenteric plexus, the state of L‐type Ca²⁺ channels or an increase in the distance between caveolae and SR affected calcium handling.