3-iodothyronamine affects thermogenic substrates’ mobilization in brown adipocytes

We investigated the effect of 3-iodothyronamine (T1AM) on thermogenic substrates in brown adipocytes (BAs). BAs isolated from the stromal fraction of rat brown adipose tissue were exposed to an adipogenic medium containing insulin in the absence (M) or in the presence of 20 nM T1AM (M+T1AM) for 6 days. At the end of the treatment, the expression of p-PKA/PKA, p-AKT/AKT, p-AMPK/AMPK, p-CREB/CREB, p-P38/P38, type 1 and 3 beta adrenergic receptors (β1–β3AR), GLUT4, type 2 deiodinase (DIO2), and uncoupling protein 1 (UCP-1) were evaluated. The effects of cell conditioning with T1AM on fatty acid mobilization (basal and adrenergic-mediated), glucose uptake (basal and insulin-mediated), and ATP cell content were also analyzed in both cell populations. When compared to cells not exposed, M+T1AM cells showed increased p-PKA/PKA, p-AKT/AKT, p-CREB/CREB, p-P38/P38, and p-AMPK/AMPK, downregulation of DIO2 and β1AR, and upregulation of glycosylated β3AR, GLUT4, and adiponectin. At basal conditions, glycerol release was higher for M+T1AM cells than M cells, without any significant differences in basal glucose uptake. Notably, in M+T1AM cells, adrenergic agonists failed to activate PKA and lipolysis and to increase ATP level, but the glucose uptake in response to insulin exposure was more pronounced than in M cells. In conclusion, our results suggest that BAs conditioning with T1AM promote a catabolic condition promising to fight obesity and insulin resistance

Surgical Treatment for a Relapsing Malleolar Bursitis in a Professional Figure Skating: Case Report

The increase of popularity in sports as Roller Skating, Figure Skating and Ice Hockey has simultaneously increased the number of skating-related injuries. Lesions of chronic dermatological nature and muscle and tendon lesions have high number of case reports. Ankle and foot are peculiarly involved and this condition suggests the correlation with the use of the skating boot, which with its high-cut and hard-fit changes the joint biomechanics and function and, as a result, the intergumentary system is continuously damaged by the compression and rubbing on the foot. The frequent onset of non-septic chronic relapsing bursitis at the level of the malleolar region is common in all sports requiring the use of skating boots. The conservative treatment is usually compromised by the repetition of the traumatic event due to the use of the skating boot. The case report of a 19 year old professional figure skater affected by non-septic relapsing malleolar bursitis at the level of the malleolar region is presented

Influence of zinc and manganese enrichments on growth, biosorption and photosynthetic efficiency of Chlorella sp

Treating biosolids from industrial, urban, and agricultural plants produces high amounts of water. After organic pollutants and non-essential heavy metals have been removed, these wastewaters are still rich in trace elements such as zinc (Zn), copper, or manganese (Mn) and have high conductivity and extremely variable pH. In this study, an isolated Chlorella sp. strain was grown for 21 days in nutrient solutions enriched with known amounts of Zn or Mn to obtain concentrations three (4.0 mg L−1)- and six (1.0 mg L−1)-fold higher than the basal medium levels, respectively, and over the limits permitted in aquatic environments. The green alga exhibited high tolerance to Zn and Mn, with the maximum abatement of Zn (28–30%) and Mn (60–63.5%) after 14 and 7 days of culture, respectively. Mn stimulated the growth rate and biomass production of Chlorella, which showed the highest carbon levels just in the first week. In both treatments, the nitrogen and protein contents remarkably increased. The photosynthetic pigments increased until the 14th day, with a higher extent in the Zn-enriched solution. An increasing photochemical efficiency was observed after 7 days of treatment, when the microalgae grown in Zn- and Mn-enriched solutions showed a slightly higher maximum photochemical efficiency than control. The autotrophic and controlled growth system adopted was designed to monitor the dynamic balance of Zn and Mn contents in the solutions and in the algal biomass. This system has proved to be useful in identifying the optimal nutritional conditions of the microalgae, along with the optimal temporal patterns of both metal biosorption capacity for water remediation and element bioaccumulation in the algal biomass

Memantine prodrug as a new agent for alzheimer’s disease

Hydrogen sulphide has recently drawn much attention due to its potent anti-inflammatory and neuroprotective roles in brain functions. The purpose of the current study was to exploit these beneficial properties of H 2 S to design a new agent for the treatment of Alzheimer’s disease (AD). To pursue our aims, we replaced the free amine group of memantine with an isothiocyanate functionality as a putative H 2 S-donor moiety. The new chemical entity, named memit, was then tested in vitro to determine whether it retains the pharmacological profile of the “native drug”, while also providing a source of H 2 S in the CNS. Indeed, Memit showed the ability to release H 2 S through a cysteine-mediated mechanism, thus generating memantine. Moreover, the new hybrid molecule exerts protective effects against neuronal inflammation and induces a drastic fall in ROS production. In addition, memit was also able to reduce the Aβ(1-42) self-induced aggregation and exerted cytoprotective effect against Aβ oligomers-induced damage in both human neurons and rat microglia cells. Finally, similarly to memantine, the new compound promotes autophagy, a complex process required for cellular homeostasis in cell survival that results to be altered in neurodegenerative diseases. In conclusion, our study revealed that memit is a prodrug of memantine. Further in vivo studies will be necessary to fully investigate the synergic or cumulative effects due to the H 2 S-releasing moiety and the native drug

Potential role of two novel agonists of thyroid hormone receptor-β on liver regeneration

Objectives: Although the hepatomitogenic activity of triiodothyronine (T3) is well established, the wide range of harmful effects exerted by this hormone precludes its use in liver regenerative therapy. Selective agonists of the beta isoform of thyroid hormone receptor (TRβ) do not exhibit T3-induced cardiotoxicity and show a good safety profile in patients with NASH. The aim of this study was to investigate whether two novel TRβ agonists, the prodrug TG68 and the active compound IS25 could stimulate hepatocyte proliferation without T3/TRα-dependent side effects. Methods: Rats were treated with three different doses (12.5, 25 and 50 μg/100 g body weight) for one week. Hepatocyte proliferation, liver injury and serum biochemical parameters were measured by immunohistochemistry, qRT-PCR and Western blot. Results: Both drugs increased hepatocyte proliferation as assessed by bromodeoxyuridine incorporation (from 14% to 28% vs 5% of controls) and mitotic activity. Enhanced proliferation occurred in the absence of significant signs of liver injury as shown by lack of increased serum transaminase levels or of apoptosis. No cardiac or renal hypertrophy typically associated with treatment with T3 was observed. Importantly, no proliferation of pancreatic acinar cells, such as that seen after administration of T3 or the TRβ agonist GC1 was detected following either TG68 or IS25, demonstrating the hepato-specificity of these novel TRβ agonists. Conclusions: The present study shows that TG68 and IS25 induce massive hepatocyte proliferation without overt toxicity. Hence, these agents may have a significant clinical application for regenerative therapies in liver transplantation or other surgical settings

Investigation of interactions between poly-l-lysine-coated boron nitride nanotubes and C2C12 cells: up-take, cytocompatibility, and differentiation

Boron nitride nanotubes (BNNTs) have generated considerable interest within the scientific community by virtue of their unique physical properties, which can be exploited in the biomedical field. In the present in vitro study, we investigated the interactions of poly-l-lysine-coated BNNTs with C2C12 cells, as a model of muscle cells, in terms of cytocompatibility and BNNT internalization. The latter was performed using both confocal and transmission electron microscopy. Finally, we investigated myoblast differentiation in the presence of BNNTs, evaluating the protein synthesis of differentiating cells, myotube formation, and expression of some constitutive myoblastic markers, such as MyoD and Cx43, by reverse transcription – polymerase chain reaction and Western blot analysis. We demonstrated that BNNTs are highly internalized by C2C12 cells, with neither adversely affecting C2C12 myoblast viability nor significantly interfering with myotube formation

Harmful Effect of Rheinheimera sp. EpRS3 (Gammaproteobacteria) Against the Protist Euplotes aediculatus (Ciliophora, Spirotrichea): Insights Into the Ecological Role of Antimicrobial Compounds From Environmental Bacterial Strains

Rheinheimera sp. strain EpRS3, isolated from the rhizosphere of Echinacea purpurea, is already known for its ability to produce antibacterial compounds. By use of culture experiments, we verified and demonstrated its harmful effect against the ciliated protist Euplotes aediculatus (strain EASCc1), which by FISH experiments resulted to harbor in its cytoplasm the obligate bacterial endosymbiont Polynucleobacter necessarius (Betaproteobacteria) and the secondary endosymbiont "Candidatus Nebulobacter yamunensis" (Gammaproteobacteria). In culture experiments, the number of ciliates treated both with liquid broth bacteria-free (Supernatant treatment) and bacteria plus medium (Tq treatment), decreases with respect to control cells, with complete disappearance of ciliates within 6 h after Tq treatment. Results suggest that Rheinheimera sp. EpRS3 produces and releases in liquid culture one or more bioactive molecules affecting E. aediculatus survival. TEM analysis of control (not treated) ciliates allowed to morphologically characterize both kind of E. aediculatus endosymbionts. In treated ciliates, collected soon after the arising of cell suffering leading to death, TEM observations revealed some ultrastructural damages, indicating that P. necessarius endosymbionts went into degradation and vacuolization after both Supernatant and Tq treatments. Additionally, TEM investigation showed that when the ciliate culture was inoculated with Tq treatment, both a notable decrease of P. necessarius number and an increase of damaged and degraded mitochondria occur. FISH experiments performed on treated ciliates confirmed TEM results and, by means of the specific probe herein designed, disclosed the presence of Rheinheimera sp. EpRS3 both inside phagosomes and free in cytoplasm in ciliates after Tq treatment. This finding suggests a putative ability of Rheinheimera sp. EpRS3 to reintroduce itself in the environment avoiding ciliate digestion