Preventive effect of vitamin D3 supplementation on conversion of optic neuritis to clinically definite multiple sclerosis: a double blind, randomized, placebo-controlled pilot clinical trial

Multiple sclerosis (MS) presents with optic neuritis (ON) in 20 % of cases and 50 % of ON patients develop MS within 15 years. In this study, we evaluated the preventive effects of vitamin D3 administration on the conversion of ON to MS (primary outcome) and on the MRI lesions (secondary outcome) of ON patients with low serum 25 (OH) D levels. Thirty ON patients (15 in each of 2 groups, aged 20–40 years) with serum 25 (OH) D levels of less than 30 ng/ml were enrolled in a double blind, randomized, parallel-group trial. The treatment group (cases) received 50,000 IU of vitamin D3 weekly for 12 months and the control group (controls) received a placebo weekly for 12 months. Finally, the subsequent relapse rate and changes in MRI plaques were compared between the two groups. Risk reduction was 68.4 % for the primary outcome in the treatment group (relative risk = 0.316, p = 0.007). After 12 months, patients in the treatment group had a significantly lower incidence rate of cortical, juxtacortical, corpus callosal, new T2, new gadolinium-enhancing lesions and black holes. The mean number of total plaques showed a marginally significant decrease in the group receiving vitamin D3 supplementation as compared with the placebo group (p = 0.092). Administration of vitamin D3 supplements to ON patients with low serum vitamin 25 (OH) D levels may delay the onset of a second clinical attack and the subsequent conversion to MS.     

Wettability of zinc oxide nanorod surfaces

In this work, we have studied the wettability of zinc oxide (ZnO) nanorods grown on fluorine-doped tin oxide (FTO) by highlighting the effect of polar and non-polar ZnO facets on contact angle (CA) results. The variation in the wettability behaviors of the synthesized surfaces is mainly related to physical and chemical surface texturing which influenced the liquid drop penetration. Indeed, three main penetration states can be deduced: total, partial, and null-penetration. Where, low CA (100.9°) with high contact angle hysteresis (CAH) (13°) is observed for total penetration of the liquid drop. While, high CA (139.6°) with low CAH (7°) is observed for null-penetration. Moreover, we have found that the chemical texturing of ZnO, especially the hydrophilicity of ZnO tips, responsible for liquid drop sticking, prevents the liquid slipping over the surface. In order to promote the liquid rolling on the ZnO surface, we reported the physical modification of the ZnO structures. Therefore, the rolling of the liquid drop on the inclined surface of ZnO is achieved by using a new structure based on double scale roughness. This surface exhibits superhydrophobic behavior with a CA of 153° and CAH of 3°.

We have studied the wettability of zinc oxide (ZnO) nanorods grown on fluorine-doped tin oxide (FTO) by highlighting the effect of polar and non-polar ZnO facets on contact angle (CA) results.     

Dual growth factor delivery from bilayered,biodegradable hydrogel composites for spatially-guided osteochondral tissue repair

The present work investigated the use of biodegradable hydrogel composite scaffolds, based on the macromer oligo(poly(ethylene glycol) fumarate) (OPF), to deliver growth factors for the repair of osteochondral tissue in a rabbit model. In particular, bilayered OPF composites were used to mimic the structural layers of the osteochondral unit, and insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) were loaded into gelatin microparticles and embedded within the OPF hydrogel matrix in a spatially controlled manner. Three different scaffold formulations were implanted in a medial femoral condyle osteochondral defect: 1) IGF-1 in the chondral layer, 2) BMP-2 in the subchondral layer, and 3) IGF-1 and BMP-2 in their respective separate layers. The quantity and quality of osteochondral repair was evaluated at 6 and 12 weeks with histological scoring and micro-computed tomography (micro-CT). While histological scoring results at 6 weeks showed no differences between experimental groups, micro-CT analysis revealed that the delivery of BMP-2 alone increased the number of bony trabecular islets formed, an indication of early bone formation, over that of IGF-1 delivery alone. At 12 weeks post-implantation, minimal differences were detected between the three groups for cartilage repair. However, the dual delivery of IGF-1 and BMP-2 had a higher proportion of subchondral bone repair, greater bone growth at the defect margins, and lower bone specific surface than the single delivery of IGF-1. These results suggest that the delivery of BMP-2 enhances subchondral bone formation and that, while the dual delivery of IGF-1 and BMP-2 in separate layers does not improve cartilage repair under the conditions studied, they may synergistically enhance the degree of subchondral bone formation. Overall, bilayered OPF hydrogel composites demonstrate potential as spatially-guided, multiple growth factor release vehicles for osteochondral tissue repair.     

The influence of age on adaptive bone formation and bone resorption

Bone is a tissue with enormous adaptive capacity, balancing resorption and formation processes. It is known that mechanical loading shifts this balance towards an increased formation, leading to enhanced bone mass and mechanical performance. What is not known is how this adaptive response to mechanical loading changes with age. Using dynamic micro-tomography, we show that structural adaptive changes of trabecular bone within the tibia of living mice subjected to two weeks of in vivo cyclic loading are altered by aging. Comparisons of 10, 26 and 78 weeks old animals reveal that the adaptive capacity diminishes. Strikingly, adaptation was asymmetric in that loading increases formation more than it reduces resorption. This asymmetry further shifts the (re)modeling balance towards a net bone loss with age. Loading results in a major increase in the surface area of mineralizing bone. Interestingly, the resorption thickness is independent of loading in trabecular bone in all age groups. This data suggests that during youth, mechanical stimulation induces the recruitment of bone modeling cells whereas in old age, only bone forming cells are affected. These findings provide mechanistic insights into the processes that guide skeletal aging in mice as well as in other mammals.     

Comparison of women versus men hospitalized with heart failure (from a 20-year registry in a middle-eastern country 1991-2010)

The aim of the present study was to compare the clinical characteristics, treatment, and outcomes of women and men hospitalized with heart failure (HF) in a Middle-Eastern country. A retrospective analysis of all patients hospitalized with HF in the State of Qatar from 1991 through 2010 was made. The clinical characteristics, management, and outcomes of the patients with HF were compared according to gender. A subset analysis according to ethnicity was also done (Middle Eastern Arabs vs South Asians). During the 20-year period, 2,379 women and 4,689 men were hospitalized for HF. The women were older and more likely to have diabetes mellitus, hypertension, and chronic renal impairment compared to the male patients. The women were less likely to be current smokers and to have ischemic heart disease compared to the men. Impaired left ventricular function was more common among men. The in-hospital mortality rates were comparable between the 2 groups (7.7% in women vs 8.2% in men; p = 0.4) and significantly improved with time in the 2 groups (p = 0.001). The mortality rates were comparable among the women, regardless of the ethnicity. In conclusion, overall improvement occurred in survival in patients hospitalized with HF in a Middle-Eastern country, regardless of gender. Women hospitalized with HF had mortality rates comparable to those of men.     

Anthracene-induced formation of highly twisted metallacycle and its crystal structure and tunable assembly behaviors

Polycyclic aromatic hydrocarbons (PAHs) continue to attract increasing interest with respect to their applications as luminescent materials. The ordered structure of the metal−organic complex facilitates the selective integration of PAHs that can be tuned to function cooperatively. Here, a unique highly twisted anthracene-based organoplatinum metallacycle was prepared via coordination-driven self-assembly. Single-crystal X-ray diffraction analysis revealed that the metallacycle was twisted through the cooperation of strong π···π stacking interactions and steric hindrance between two anthracene-based ligands. Notably, the intramolecular twist and aggregation behavior introduced restrictions to the conformational change of anthracenes, which resulted in increased emission intensity of the metallacycle in solution. The emission behaviors and suprastructures based on the highly twisted metallacycle can be modulated by the introduction of different solvents. This study demonstrates that this metallacycle with highly twisted structure is a promising candidate for sensing and bioimaging applications.

Weak intermolecular interactions play an essential role in the construction of well-defined hierarchical architectures with high complexity and functionality (1–4). In nature, a complex interplay of units forms highly organized suprastructures (5). From biofilms to cells, tissues, and organs, orderliness starts with the lipid bilayer and ultimately results in the formation of a macroscopically visible specific shape through multilevel assembly (6). Structurally, any macroscale organism maintains a high degree of orderliness on an extremely small scale, and this multilevel orderliness is carried through to the macroscale (7). DNA and histones coassemble to form chromatids, and chromatids further assemble to form chromosomes (8). Inspired by assemblies in the natural world, researchers have created diverse suprastructures with distinct spatial arrangements via weak interactions, such as hydrogen bonds, aromatic stacking, and hydrophobic interactions (9–19). Among these, coordination-driven self-assembly (CDSA) provides a powerful strategy for producing metal organic complexes (MOCs) with various sizes, shapes, and metal/ligand stoichiometries (20–26). To date, diverse MOCs have been developed by coordination between metal ions and organic ligands, and these exhibit superiority over their precursors and can be used in emission units, sensors, and hosts as well as in applications in biomedical diagnosis and catalysis (27–34). Platinum-based architectures are the most extensively studied of these structures and have undergone the most rapid development, due to their facile synthesis (35–39).Platinum-based metallacycles are desirable candidates for the construction of luminophores because of their structural versatility. However, most luminophores always suffer from aggregation-induced quenching at high concentrations or in the solid state. Aggregation-induced emission has been employed in the fields of sensors, bioimaging, and drug delivery, due to strong emissions in the aggregated state (40, 41). However, to date, a tetraphenylethylene moiety is required in the construction of metallacycles with emission (42) Anthracene (ANTHR) is an attractive moiety that endows suprastructures with unique optical properties due to its extended π-surface (43, 44), which results in the formation of promising candidates for light emitters (45), photocatalysts (46), and data storage materials (47). For example, Zr and Fe have been incorporated with ANTHR into coordination complexes to perform catalysis (48) and to mimic the functional behavior of enzymes (49). In addition, ANTHR-based rectangles have been proven to provide near-infrared emission for application in ammonia detection (50), and ANTHR-based hexagons have been used for the capture and release of singlet oxygen (51). However, most reported ANTHR-based metallacycles have planar structures. Considering the relationship between structure and function of these metallacycles, the development of more structures with new steric features will lead to the emergence of new functions. This study provides an ANTHR-based metallacycle with a highly twisted conformation among ligands, and the twist angle between ANTHR is close to 90°. Benefiting from this highly twisted structure induced by intramolecular restriction, ANTHR-containing metallacycle with aggregation-induced emission was observed.     

Synthesis and evaluation of antimicrobial activity,cytotoxic and pro-apoptotic effects of novel spiro-4H-pyran derivatives

A new library of spiropyrans were synthesized via a one-pot four component reaction of cyanoacetohydrazide, ninhydrin, malononitrile and various cyclic CH-acids in EtOH at reflux conditions. The products were isolated and tested in vitro for antibacterial effects on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Furthermore cytotoxic activity of the spiropyrans on non-small-cell lung cancer cells (A549 cells), a breast epithelial cancer cell line (MCF-7), human malignant melanoma cells (A375), prostate cancer cells (PC3 cells, LNCaP cells) and normal cells HDF (human dermal fibroblast) was investigated. Interestingly, it was found that compounds 5a, 5b, 5f, 5g and 5i have the best MIC against S. auerus and compound 5a displayed the most potent activity against A549, A375, and LNCaP tumor cells. Moreover, DAPI staining of the A549 cancer cell lines that were treated with 5a were associated with the death of A549 cells. By using RT-PCR method, it was finally confirmed that apoptosis occurs in A549 cells by up-regulated Bax expression and down-regulated Bcl-2 expression from the mitochondrial pathway of apoptosis.

Evalution of anti-microbial activity, cytotoxic and pro-apoptotic effects of novel synthesized fused spiro-4H-pyran derivatives.     

Hormonal markers as noninvasive predictors of sperm retrieval in non-obstructive azoospermia

Non-obstructive azoospermia (NOA) is one of the leading causes of male factor infertility, which results from impaired spermatogenesis. Currently, the sole feasible therapeutic option for men with NOA to father their biologic children is sperm retrieval by testicular sperm extraction (TESE) approaches followed by an intracytoplasmic sperm injection program. Nevertheless, the rate of sperm retrieval from NOA men following TESE has remained as low as 50%, leading to a significant number of unsuccessful TESE operations. Given that TESE is associated with multiple side effects, the prediction of TESE outcome preoperatively can abolish unnecessary operations and thereby prevent NOA patients from sustaining adverse side effects. As the process of spermatogenesis is under the regulation of hormones, the hormonal profile of serum and/or seminal plasma may contain useful information about spermatogenesis status and can potentially predict the chance of sperm retrieval from NOA patients. A large body of literature is available on the predictive capability of different serum and seminal plasma hormones such as FSH, LH, testosterone, inhibin B, AMH, estradiol, prolactin, and leptin in a stand-alone basis or combinational fashion with respect to the TESE outcome. The present review aimed to evaluate the potential of these hormonal markers as noninvasive predictors of sperm retrieval in men with NOA.

     

Invariant NKT cells reduce the immunosuppressive activity of influenza A virus–induced myeloid-derived suppressor cells in mice and humans

Infection with influenza A virus (IAV) presents a substantial threat to public health worldwide, with young, elderly, and immunodeficient individuals being particularly susceptible. Inflammatory responses play an important role in the fatal outcome of IAV infection, but the mechanism remains unclear. We demonstrate here that the absence of invariant NKT (iNKT) cells in mice during IAV infection resulted in the expansion of myeloid-derived suppressor cells (MDSCs), which suppressed IAV-specific immune responses through the expression of both arginase and NOS, resulting in high IAV titer and increased mortality. Adoptive transfer of iNKT cells abolished the suppressive activity of MDSCs, restored IAV-specific immune responses, reduced IAV titer, and increased survival rate. The crosstalk between iNKT and MDSCs was CD1d- and CD40-dependent. Furthermore, IAV infection and exposure to TLR agonists relieved the suppressive activity of MDSCs. Finally, we extended these results to humans by demonstrating the presence of myeloid cells with suppressive activity in the PBLs of individuals infected with IAV and showed that their suppressive activity is substantially reduced by iNKT cell activation. These findings identify what we believe to be a novel immunomodulatory role of iNKT cells, which we suggest could be harnessed to abolish the immunosuppressive activity of MDSCs during IAV infection.