Secreted factors from ventral telencephalon induce the differentiation of GABAergic neurons in cortical cultures

It is widely believed that the pyramidal cells and interneurons of the cerebral cortex are distinct in their origin, lineage and genetic make up. In view of these findings, the current thesis is that the phenotype determination of cortical neurons is primarily directed by genetic mechanisms. Using in vitro assays, the present study demonstrates that secreted factors from ganglionic eminence (GE) of the ventral telencephalon have the potency to induce the differentiation of a subset of cortical neurons towards gamma-aminobutyric acid (GABA)ergic lineage. Characterization of cortical cultures that were exposed to medium derived from GE illustrated a significant increase in the number of GABA-, calretinin- and calbindin-positive neurons. Calcium imaging together with pharmacological studies showed that the application of exogenous medium significantly elevated the intracellular calcium transients in cortical neurons through the activation of ionotropic glutamate receptors. The increase in GABA+ neurons appeared to be associated with the elevated calcium activity; treatment with blockers specific for glutamate receptors abolished both the synchronized transients and reduced the differentiation of GABAergic neurons. Such studies demonstrate that although intrinsic mechanisms determine the fate of cortical interneurons, extrinsic factors have the potency to influence their neurochemical differentiation and contribute towards their molecular diversity.     

The rise and rise of stealth nanocarriers for cancer therapy: passive versus active targeting

Research in designing and engineering long-circulating nanoparticles, so-called 'stealth' nanoparticles, has been attracting increasing interest as a new platform for targeted drug delivery, especially in chemotherapy. In particular, the modification of nanoparticulate surfaces with poly(ethylene glycol) derivatives has illustrated a decreased uptake of nanoparticles by mononuclear phagocyte system cells and, hence, an increased circulation time, allowing passive accumulation in the tumor. The clinical trials on patients with solid tumors are described in this article, to illustrate this generation of promising nanoparticles. In the last few years, the new-generation technique of grafting ligands on the nanoparticle surface in order to target and penetrate specific cancer cells has been developed. This article discusses the benefits of passive targeting for drug delivery to the solid tumors via the enhanced permeability and retention effect, when using stealth nanoparticles, and compares them with the advantages of active targeting.     

Characterizations and Antibacterial Efficacy of Chitosan Oligomers Synthesized by Microwave-Assisted Hydrogen Peroxide Oxidative Depolymerization Method for Infectious Wound Applications

The use of naturally occurring materials with antibacterial properties has gained a great interest in infected wound management. Despite being an abundant resource in Vietnam, chitosan and its derivatives have not yet been intensively explored for their potential in such application. Here, we utilized a local chitosan source to synthesize chitosan oligomers (OCS) using hydrogen peroxide (H₂O₂) oxidation under the microwave irradiation method. The effects of H₂O₂ concentration on the physicochemical properties of OCS were investigated through molecular weight, degree of deacetylation, and heavy metal contamination for optimization of OCS formulation. Then, the antibacterial inhibition was examined; the minimum inhibitory concentration and minimum bactericidal concentration (MIC and MBC) of OCS-based materials were determined against common skin-inhabitant pathogens. The results show that the local Vietnamese chitosan and its derivative OCS possessed high-yield purification while the molecular weight of OCS was inversely proportional and proportional to the concentration of H₂O₂, respectively. Further, the MIC and MBC of OCS ranged from 3.75 to less than 15 mg/mL and 7.5–15 mg/mL, respectively. Thus, OCS-based materials induce excellent antimicrobial properties and can be attractive for wound dressings and require further investigation.     

Polymers based on thieno[3,4-c]pyrrole-4,6-dione and pyromellitic diimide by CH–CH arylation reaction for high-performance thin-film transistors

Three homopolymers were successfully synthesized by direct CH–CH arylation polymerization of thieno[3,4-c]pyrrole-4,6-dione or pyromellitic diimide derivatives affording highly purified polymers with high molecular weights (43.0–174.7 K). Thieno[3,4-c]pyrrole-4,6-dione and pyromellitic diimide derivatives are considered as electron-withdrawing units. The synthesized homopolymers P1, P2, and P3 showed band gaps in the range of 2.13–2.08 eV, respectively. The electron mobilities of the three homopolymers have been investigated. The thin film transistor for P1 prepared by the eutectic-melt-assisted nanoimprinting method achieved an electron mobility of 2.11 × 10⁻³ cm² s⁻¹ V⁻¹. Based on the obtained results, the synthesized polymers can be used as potential electron acceptors in solar cell applications.

The homopolymers P1, P2 and P3 were successfully synthesized by direct CH–CH arylation polymerization in an eco-friendly one-step coupling reaction. They present n-type properties for potential applications as acceptor polymers.     

Miconazole, a pharmacological barrier to skin fungal infections

INTRODUCTION: Miconazole (MCZ) is a time-honored antifungal of the imidazole class. MCZ exerts a multipronged effect on fungi. It inhibits the cytochrome P450 complex, including the 14α-demethylase enzyme required for ergosterol biosynthesis, in fungal cell membranes. In addition, intracellular accumulation of toxic methylated sterols occurs and the synthesis of triglycerides and phospholipids is altered. Disturbances in oxidative and peroxidative enzyme activities lead to an intracellular toxic concentration of hydrogen peroxide. As a result, intracellular organelle destruction then leads to cell necrosis. Farnesol synthesis stimulated in Candida spp. prevents the yeast-to-mycelium formation. MCZ is further active against Gram-positive bacteria. AREAS COVERED: This review aims at revisiting the MCZ antifungal activity in dermatomycoses. EXPERT OPINION: MCZ's wide spectrum of activity appears noteworthy. The full pharmacological profile of MCZ indicates its fungistatic profile through its effect on ergosterol biosynthesis. In addition, it exhibits a fungicidal effect against a number of fungal species, due to hydrogen peroxide accumulation. MCZ is characterized by high safety, efficacy and versatility, and a unique, multifaceted nature of activity in the treatment of dermatomycoses.     

Is a Treatment Delay in Radical Prostatectomy Safe in Individuals with Low‐Risk Prostate Cancer?

IntroductionMany patients diagnosed with localized prostate cancer (PCa) are presented with several treatment modalities, which may require time to understand these options before making an informed decision regarding treatment.AimThe aim of this study was to compare the effect of radical prostatectomy (RP) delay on postoperative functional outcomes and mortality in a North American population‐based cohort.MethodsOverall, 17,153 men treated with RP for non‐metastatic clinical stage T1–2, low‐grade PCa between years 1995 and 2005 within the U.S. Surveillance, Epidemiology, and End Results Medicare‐linked database were abstracted.Main Outcome MeasuresThe effect of treatment delay (from PCa diagnosis to RP of >3 months) on pathological upstaging at surgery (≥pT3) and postoperative functional outcomes (urinary incontinence and erectile dysfunction) was examined using logistic regression analyses. The 10‐year PCa mortality rates were computed using cumulative incidence rates.ResultsOverall, 2,576 (15%) patients underwent RP > 3 months after diagnosis. A treatment delay of >3 months was associated with a 24% and 33% higher rate of erectile dysfunction diagnosis and procedure, respectively (both P ≤ 0.001). Treatment delay was also associated with 6% higher rate of urinary incontinence procedure (P = 0.01). Furthermore, a dose‐response effect was detected with respect to increasing durations of RP delay (≤3 vs. 3–5 vs. 5–9 vs. ≥9 months) the rates of erectile dysfunction and urinary incontinence diagnoses/procedures. Treatment delay was not associated with pathological upstaging and PCa mortality.ConclusionsCustomarily, the timing of RP following biopsy is dictated by tumor aggressiveness. In general, patients with more unfavorable characteristics are operated sooner. This may obliterate the potential detriments of delayed RP. The treatment delay between biopsy and RP may result in more extensive periprostatic tissue resection and may adversely affect postoperative continence and erectile function. Sun M, Abdollah F, Hansen J, Trinh Q‐D, Bianchi M, Tian Z, Briganti A, Shariat SF, Montorsi F, Perrotte P, and Karakiewicz PI. Is a treatment delay in radical prostatectomy safe in individuals with low‐risk prostate cancer? J Sex Med 2012;9:2961–2969.     

Acupuncture for obesity: a systematic review

Obesity has become a major health challenge for both patients and family physicians. Well-known methods of weight reduction such as diet and exercise are often difficult to comply with due to lifestyle and quality of life issues. Other methods such as diet pills or surgery have potentially serious side effects and often do not show long-term benefit. In an attempt to find a less invasive and effective modality of treatment, traditional Chinese medicine, particularly acupuncture and auriculotherapy, has become a topic of research in this field. The authors conducted a review of the current evidence regarding the use of auricular and body acupuncture in the treatment of obesity from their beginning to June 2014. Any published trial using randomized assignment to the intervention and control groups, in full text were included. Overall, moderate evidence in favor of acupuncture over exercise in the treatment of obesity was found. However, due to the limitations of the published studies in this field, it is necessary to conduct a large high quality randomized controlled trial in order to determine whether acupuncture should be used as a treatment modality to achieve weight loss in obese individuals.