Hybrid nanoreservoirs based on dextran-capped dendritic mesoporous silica nanoparticles for CD133-targeted drug delivery

In this study, the chemical features of dendritic mesoporous silica nanoparticles (DMSNs) provided the opportunity to design a nanostructure with the capability to intelligently transport the payload to the tumor cells. In this regard, doxorubicin (DOX)-encapsulated DMSNs was electrostatically surface-coated with polycarboxylic acid dextran (PCAD) to provide biocompatible dextran-capped DMSNs (PCAD-DMSN@DOX) with controlled pH-dependent drug release. Moreover, a RNA aptamer against a cancer stem cell (CSC) marker, CD133 was covalently attached to the carboxyl groups of DEX to produce a CD133-PCAD-DMSN@DOX. Then, the fabricated nanosystem was utilized to efficiently deliver DOX to CD133+ colorectal cancer cells (HT29). The in vitro evaluation in terms of cellular uptake and cytotoxicity demonstrated that the CD133-PCAD-DMSN@DOX specifically targets HT29 as a CD133 overexpressed cancer cells confirmed by flow cytometry and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. The potentially promising intelligent-targeted platform suggests that targeted dextran-capped DMSNs may find impressive application in cancer therapy.     

Bactericidal and bacteriostatic antigonococcal activities produced by urogenital staphylococci

We have overcome some of the difficulties in obtaining soluble antigonococcal activity produced by staphylococci by using a very sensitive detection method. This method is based on the light absorbance determinations of liquid cultures of the gonococcus incubated for 6 h in the presence of serial dilutions of the inhibitor as compared to the absorbance of uninhibited control cultures. Antigonococcal activity was detected in the liquid phase prepared from semisolid agar cultures of all twenty two staphylococcal isolates tested. Sixteen supernatants from liquid cultures were also found to be active. The antigonococcal activity detected was differentiated by colony forming units counts into two types, bacteriostatic and bactericidal. After 6 h of incubation of the gonococcus in the presence of five arbitrary units (AU)/ml of the bactericidal activity produced by one of the strains of staphylococci, isolate 37, the loss of viability was over 99.9%, while 10 AU/ml of the bacteriostatic activity produced by isolate 66 did not cause any loss of viability of the gonococcus.     

Effect of the conditioned medium of mesenchymal stem cells on the expression levels of P2X4 and P2X7 purinergic receptors in the spinal cord of rats with neuropathic pain

Purinergic Signalling - Recent studies have shown that mesenchymal stem cells (MSCs) and their conditioned medium (CM) have potential therapeutic effects in animal models of neuropathic pain (NP)....     

Prediction of shape and internal structure of the proximal femur using a modified level set method for structural topology optimisation

A computational framework was developed to simulate the bone remodelling process as a structural topology optimisation problem. The mathematical formulation of the Level Set technique was extended and then implemented into a coronal plane model of the proximal femur to simulate the remodelling of internal structure and external geometry of bone into the optimal state. Results indicated that the proposed approach could reasonably mimic the major geometrical and material features of the natural bone. Simulation of the internal bone remodelling on the typical gross shape of the proximal femur, resulted in a density distribution pattern with good consistency with that of the natural bone. When both external and internal bone remodelling were simulated simultaneously, the initial rectangular design domain with a regularly distributed mass reduced gradually to an optimal state with external shape and internal structure similar to those of the natural proximal femur.     

An integrated analysis to predict micro‐RNAs targeting both stemness and metastasis in breast cancer stem cells

Several evidences support the idea that a small population of tumour cells representing self‐renewal potential are involved in initiation, maintenance, metastasis, and outcomes of cancer therapy. Elucidation of microRNAs/genes regulatory networks activated in cancer stem cells (CSCs) is necessary for the identification of new targets for cancer therapy. The aim of the present study was to predict the miRNAs pattern, which can target both metastasis and self‐renewal pathways using integration of literature and data mining. For this purpose, mammospheres derived from MCF‐7, MDA‐MB231, and MDA‐MB468 were used as breast CSCs model. They had higher migration, invasion, and colony formation potential, with increasing in stemness‐ and EMT‐related genes expression. Our results determined that miR‐204, ‐200c, ‐34a, and ‐10b contemporarily could target both self‐renewal and EMT pathways. This core regulatory of miRNAs could increase the survival rate of breast invasive carcinoma via up‐regulation of OCT4, SOX2, KLF4, c‐MYC, NOTCH1, SNAI1, ZEB1, and CDH2 and down‐regulation of CDH1. The majority of those target genes were involved in the regulation of pluripotency, MAPK, WNT, Hedgehog, p53, and transforming growth factor β pathways. Hence, this study provides novel insights for targeting core regulatory of miRNAs in breast CSCs to target both self‐renewal and metastasis potential and eradication of breast cancer.     

2-(Bipiperidin-1-yl)-5-(nitroaryl)-1,3,4-thiadiazoles: Synthesis,evaluation of in vitro leishmanicidal activity,and mechanism of action

The development of novel leishmanicidal agents that are capable of being replaced by the available therapeutic options has become a priority. In the present study, the synthesis and leishmanicidal activity of a series of 5-(nitroheteroaryl-2-yl)-1,3,4-thiadiazole derivatives are described. All compounds appeared to be potent anti-leishmanial agents against both promastigote and amastigote forms of Leishmania major (L. major). Amongst the synthesized compounds, 2-([1,4′-bipiperidin]-1′-yl)-5-(5-nitrofuran-2-yl)-1,3,4-thiadiazole (IIa) and 1-(5-(1-methyl-5-nitro-1H-imidazole-2-yl)-1,3,4-thiadiazol-2-yl)-4-(piperidine-1-yl) piperidine (IIc) are the most effective. Infection index was statistically declined in the presence of all compounds. The analysis of redox-related factors revealed that exposure of L. major cells to IIa and IIc led to an increase in reactive oxygen species (ROS). Furthermore, two compounds were able to increase ROS and NO levels in infected macrophages in a dose-independent manner. In addition, we showed that these compounds induced cell death in promastigotes. Altogether, our results indicated the anti-leishmanial potential of IIa and IIc is mediated by apoptosis through an imbalance in the redox system resulting in the elevation of ROS. This new class of compound seems to hold great promise for the development of new and useful anti-leishmanial agents.     

Effects of Probiotic Yogurt on Serum Omentin-1, Adropin,and Nesfatin-1 Concentrations in Overweight and Obese Participants Under Low-Calorie Diet

Probiotics and Antimicrobial Proteins - Data on the effects of probiotics on adipokines such as omentin-1, nesfatin-1, and adropin are limited. The aim of this study was to evaluate the effects of...     

Magnetoelectric nanocomposite scaffold for high yield differentiation of mesenchymal stem cells to neural-like cells

While the differentiation factors have been widely used to differentiate mesenchymal stem cells (MSCs) into various cell types, they can cause harm at the same time. Therefore, it is beneficial to propose methods to differentiate MSCs without factors. Herein, magnetoelectric (ME) nanofibers were synthesized as the scaffold for the growth of MSCs and their differentiation into neural cells without factors. This nanocomposite takes the advantage of the synergies of the magnetostrictive filler, CoFe₂O ₄ nanoparticles (CFO), and piezoelectric polymer, polyvinylidene difluoride (PVDF). Graphene oxide nanosheets were decorated with CFO nanoparticles for a proper dispersion in the polymer through a hydrothermal process. After that, the piezoelectric PVDF polymer, which contained the magnetic nanoparticles, underwent the electrospun process to form ME nanofibers, the ME property of which has the potential to be used in areas such as tissue engineering, biosensors, and actuators.     

Chitosan-based delivery systems for curcumin: A review of pharmacodynamic and pharmacokinetic aspects

Effective drug delivery is one of the most important issues associated with the administration of therapeutic agents that have low oral bioavailability. Curcumin is an active ingredient in the turmeric plant, which has low oral bioavailability due to its poor aqueous solubility. One strategy that has been considered for enhancing the aqueous solubility, and, thus, its oral bioavailability, is the use of chitosan as a carrier for curcumin. Chitosan is a biodegradable and biocompatible polymer that is relatively water-soluble. Therefore, various studies have sought to improve the aqueous solubility of chitosan. The use of different pharmaceutical excipients and formulation strategies has the potential to improve aqueous solubility, formulation processing, and the overall delivery of hydrophobic drugs. This review focuses on various methods utilized for chitosan-based delivery of curcumin.     

MicroRNA in leukemia: Tumor suppressors and oncogenes with prognostic potential

Leukemia is known as a progressive malignant disease, which destroys the blood-forming organs and results in adverse effects on the proliferation and development of leukocytes and their precursors in the blood and bone marrow. There are four main classes of leukemia including acute leukemia, chronic leukemia, myelogenous leukemia, and lymphocytic leukemia. Given that a variety of internal and external factors could be associated with the initiation and progression of different types of leukemia. One of the important factors is epigenetic regulators such as microRNAs (miRNAs) and long noncoding RNAs (ncRNA). MiRNAs are short ncRNAs which act as tumor suppressor (i.e., miR-15, miR-16, let-7, and miR-127) or oncogene (i.e., miR-155, miR-17-92, miR-21, miR-125b, miR-93, miR-143-p3, miR-196b, and miR-223) in leukemia. It has been shown that deregulation of these molecules are associated with the initiation and progression of leukemia. Hence, miRNAs could be used as potential therapeutic candidates in the treatment of patients with leukemia. Moreover, increasing evidence revealed that miRNAs could be used as diagnostic and prognostic biomarkers in monitoring patients in early stages of disease or after received chemotherapy regimen. It seems that identification and development of new miRNAs could pave to the way to the development new therapeutic platforms for patients with leukemia. Here, we summarized various miRNAs as tumor suppressor and oncogene which could be introduced as therapeutic targets in treatment of leukemia.