A review of key challenges of electrospun scaffolds for tissue‐engineering applications

Tissue engineering holds great promise to develop functional constructs resembling the structural organization of native tissues to improve or replace biological functions, with the ultimate goal of avoiding organ transplantation. In tissue engineering, cells are often seeded into artificial structures capable of supporting three‐dimensional (3D) tissue formation. An optimal scaffold for tissue‐engineering applications should mimic the mechanical and functional properties of the extracellular matrix (ECM) of those tissues to be regenerated. Amongst the various scaffolding techniques, electrospinning is an outstanding one which is capable of producing non‐woven fibrous structures with dimensional constituents similar to those of ECM fibres. In recent years, electrospinning has gained widespread interest as a potential tissue‐engineering scaffolding technique and has been discussed in detail in many studies. So why this review? Apart from their clear advantages and extensive use, electrospun scaffolds encounter some practical limitations, such as scarce cell infiltration and inadequate mechanical strength for load‐bearing applications. A number of solutions have been offered by different research groups to overcome the above‐mentioned limitations. In this review, we provide an overview of the limitations of electrospinning as a tissue‐engineered scaffolding technique, with emphasis on possible resolutions of those issues. Copyright © 2015 John Wiley & Sons, Ltd.     

Expression of deoxynucleoside kinases and 5'-nucleotidases in mouse tissues: implications for mitochondrial toxicity

Anti-HIV nucleoside therapy can result in mitochondrial toxicity affecting muscles, peripheral nerves, pancreas and adipose tissue. The cytosolic deoxycytidine kinase (dCK; EC 2.7.1.74) and thymidine kinase (TK1; EC 2.7.1.21), the mitochondrial thymidine kinase (TK2) and deoxyguanosine kinase (dGK; EC 2.7.1.113) as well as 5'-deoxynucleotidases (5'-dNT; EC 3.1.3.5) are enzymes that control rate-limiting steps in formation of intracellular and intra-mitochondrial nucleotides. The mRNA levels and activities of these enzymes were determined in mouse tissues, using real-time PCR and selective enzyme assays. The expression of mRNA for all these enzymes and the mitochondrial deoxynucleotide carrier was detected in all tissues with a 5-10-fold variation. TK1 activities were only clearly detected in spleen and testis, while TK2, dGK and dCK activities were found in all tissues. dGK activities were higher than any other dNK in all tissues, except spleen and testis. In skeletal muscle dGK activity was 5-fold lower, TK2 and dCK levels were 10-fold lower as compared with other tissues. The variation in 5'-dNT activities was about eight-fold with the highest levels in brain and lowest in brown fat. Thus, the salvage of deoxynucleosides in muscles is 5-10-fold lower as compared to other non-proliferating tissues and 100-fold lower compared to spleen. These results may help to explain tissue specific toxicity observed with nucleoside analogs used in HIV treatment as well as symptoms in inherited mitochondrial TK2 deficiencies.     

A Protocol for Management of the Hairs Problem in Oral Cavity Reconstruction by Submental Flap

Background

Submental flap is a useful aid in maxillofacial reconstruction. For intraoral usage the hairs in male patients will create some problems.

Materials and Methods

In a retrospective study, patients in whom submental flap had been used for reconstruction of orofacial region between 2007 and 2013, in the Mashhad University, Ghaem Hospital, were included. The ways in which the problem of hairs was solved in male patients were evaluated.

Results

There were 42 patients in whom submental flap was used for orofacial reconstruction. Sixty percent were males. Three ways had been used for management of intraoral hairs: radiotherapy (9 patients), second surgery (2 patients) and flap de-epithelialization (13 patients).

Conclusion

Deepithelialized variant of submental flap is the best option when submental flap is used for oral cavity reconstruction in male patients. Flap thickness, age, race and postoperative radiotherapy can have strong influence on this strategy.

     

Synthesis and cytotoxic properties of novel (E)-3-benzylidene-7-methoxychroman-4-one derivatives

Background and the purpose of the study

There has been increscent interest in the field of cancer chemotherapy by discovery and development of novel agents with high efficacy, low toxicity, and minimum side effects. In order to find new anticancer agents, we replaced the pyrazolone part of well-known cytotoxic agent SJ-172550 with 7-methoxychroman-4-one. Thus, a novel series of 3-benzylidene-4-chromanones were synthesized and tested in vitro against human cancer cell lines.

Methods

The title compounds were prepared by condensation of 7-methoxychroman-4-one with suitable aldehydes in appropriate alcohol in the presence of gaseous HCl. The antiproliferative activity of target compounds were evaluated against MDA-MB-231 (breast cancer), KB (nasopharyngeal epidermoid carcinoma) and SK-N-MC (human neuroblastoma) cell lines using MTT assay.

Results

Although the direct analog of SJ-172550 (compound 5d) did not show any cytotoxic activity against tested cell lines, but 2-(2-chloro-6-methoxyphenoxy)acetic acid methyl ester analog 5c showed some activity against MDA-MB-231 and SK-N-MC cells. Further modification of compound 5c resulted in the 3-chloro-4,5-dimethoxybenzylidene derivative 5b which demonstrated better cytotoxic profile against all tested cell lines (IC₅₀ values = 7.56–25.04 μg/ml).

Conclusion

The results demonstrated that the cytotoxic activity of compound 5b against MDA-MB-231 and SK-N-MC cells is more than etoposide. Therefore, compound 5b prototype could be considered as novel cytotoxic agent for further developing new anticancer chemotherapeutics.     

Diagnostic histological features of metastatic lymph nodes in adenosquamous carcinoma

Laryngeal adenosquamous carcinoma (ASC) is a rare malignancy, and the problems in true diagnosis of this entity are well known. In this paper, we describe a case of ASC and discuss its distinct histopathology in metastatic lymph nodes. A heavy smoker man presented with a progressive neck mass. Based on incisional biopsy, diagnosis of squamous cell carcinoma (SCC) was made and total laryngectomy with bilateral radical neck dissection was performed. Sections of primary tumor showed a well-differentiated SCC. However, lymph node metastases had a distinct feature of glandular structures. Further investigation with Mayer's mucicarmine stain confirmed the presence of rare scattered glands in primary tumor and the final diagnosis was changed to ASC. Adenosquamous carcinoma is a distinct entity and must be distinguished from the common SCC of larynx. As a result, when a lesion with diagnosis of squamous cell carcinoma shows evidence of glandular differentiation in a subsequent biopsy or in nodal metastases, more investigation is necessary. Moreover, the glandular structures in primary tumor, as in this case, may be rare and inconspicuous. Therefore, we suggest the precise evaluation of metastatic lymph nodes for any laryngeal tumor with diagnosis of SCC. This helps to make appropriate therapeutic decisions with respect to the aggressive behavior of ASC and its high propensity for lymph node metastasis.     

Tioxolone niosomes exert antileishmanial effects on Leishmania tropica by promoting promastigote apoptosis and immunomodulation

Objective: To explore the antileishmanial effect of tioxolone and its niosomal form against Leishmania tropica. Methods: Tioxolone niosomes were prepared by the hydration method and were evaluated for morphology, size, release study, and encapsulation efficiency. The cytotoxicity of tioxolone and its niosomal form was measured by MTT assay, leishmanicidal activity against promastigote and amastigote by MTT assay, apoptosis by flow cytometry, IL-12, IL-10 and metacaspase gene expression levels by q-PCR. Results: Span/Tween 40 and Span/Tween 60 niosomes had good physical stability as depicted in their size distribution curves and high encapsulation efficiency(99%). The release profile of the entrapped compounds showed Fickian's model of tioxolone delivery based on diffusion through lipid bilayers. With the IC50 value for amastigote as(24.5±2.1) μg/mL and selectivity index as 10.5, the Span/Tween 60 niosome(NT2) had a superior effect to other drugs. The CC50 value and IC50 of promastigote value for NT2 were(257.5±24.5) μg/mL and(164.8±20.6) μg/mL, respectively. The flow cytometric analysis showed that tioxolone and niosomal forms induced apoptosis of Leishmania tropica promastigotes in a dose-dependent manner. NT2 increased the expression level of IL-12 and metacaspase genes and decreased the expression level of the IL-10 gene.Conclusions: Niosomes of tioxolone play an immunomodulatory role in increasing Th1 cytokine profile and inhibiting the Th2 cytokine profile. It could be used for treatment of anthroponotic cutaneous leishmaniasis.