TBAI-Mediated Cyclization and Methylsulfonylation of Propargylic Amides with Dimethyl Sulfite.

A tetramethylammonium iodide (TBAI)-mediated cyclization and methylsulfonylation of propargylic amides enabled by dimethyl sulfite as a SO2 surrogate and methyl source have been developed. The transition metal-free and oxidant-free reaction provides a practical and efficient approach for the selective synthesis of methylsulfonyl oxazoles in moderate to excellent yields with good functional group compatibility.

Palladium-Catalyzed Methylsulfonylation of Alkyl Halides Using Dimethyl Sulfite as SO2 Surrogate and Methyl Source.

A novel and efficient method for the synthesis of methyl sulfone derivatives via palladium-catalyzed methylsulfonylation of alkyl halides with dimethyl sulfite has been described. A variety of aryl and alkyl iodides underwent the sulfonylation smoothly to furnish methyl sulfites in moderate to excellent yields.

Iodine-promoted ring-opening methylation of benzothiazoles with dimethyl sulfite.

A halogen-bond promoted ring-opening methylation of benzothiazoles has been developed using dimethyl sulphite as a methylating reagent in the presence of a base. This approach represents a simple and efficient synthesis of N-methyl-N-(o-methylthio)phenyl amides, and features direct construction of both N-Me and S-Me bonds in a one-pot reaction through the decomposition of easily prepared benzothiazoles.

CTHRC1 promotes wound repair by increasing M2 macrophages via regulating the TGF-ß and notch pathways.

The healing of acute wounds is vital to humans and is a well-orchestrated process that involves systemic and local factors. However, there is a lack of effective and safe clinical therapies. The collagen triple helix repeat containing 1 (CTHRC1) protein is a type of exocrine protein that has been recently reported to contribute to tissue repair. Our aim is to validate the promoting effects of CTHRC1 on the healing of acute wounds and to elucidate the underlying molecular mechanism. Therefore, we first established acute wound healing mouse models and confirmed that CTHRC1 accelerates the healing process of acute wounds. Then, we characterized wound macrophages using a polyvinylalcohol (PVA) sponge model and used Western blotting to investigate the molecular mechanism. We found that CTHRC1 increased the M2 macrophage population and the TGF-ß expression level as a result of the activation of the TGF-ß and Notch pathways, which eventually contributed to the promotion of wound healing. Inhibition of the Notch pathway showed attenuated M2 macrophage recruitment, and it decreased the TGF-ß expression level. These results substantiate our hypothesis that CTHRC1 promotes wound healing by recruiting M2 macrophages and regulating the TGF-ß and Notch pathways.

Copper-mediated stereospecific C-H oxidative sulfenylation of terminal alkenes with disulfides.

A copper and iodine-mediated C-H oxidative sulfenylation of olefins with diaryl disulfides has been developed for the stereospecific synthesis of vinyl thioether. With the combination of Cu(OTf)2 and I2, a variety of terminal alkenes underwent oxidative coupling reaction with various diaryl disulfides successfully to afford the corresponding E-vinyl sulfides in moderate to good yields.

Palladium-catalyzed oxidative carbamoylation of isoquinoline N-oxides with formylamides by means of dual C-H oxidative coupling.

A new palladium-catalyzed oxidative carbamoylation reaction of isoquinoline N-oxides with formylamides for the synthesis of isoquinoline-1-carboxamides is established. The method represents the first example of the carbamoylation of isoquinoline N-oxides with formylamides to furnish arylamides using the dual C-H oxidation strategy.

Suppressive effects of induced pluripotent stem cell-conditioned medium on in vitro hypertrophic scarring fibroblast activation.

Hypertrophic scarring (HS) is a type of fibrosis that occurs in the skin, and is characterized by fibroblast activation and excessive collagen production. However, at present, therapeutic strategies for this condition are ineffective. Previous studies have identified that the mutual regulation of chronic inflammation, mechanical force and fibroblast activation leads to the formation of HS. Induced pluripotent stem cells (iPSCs) are novel bioengineered embryonic­like stem cells, initially created from mouse adult fibroblasts. The current study demonstrated that iPSC­conditioned medium (iPSC­CM) may significantly suppress hypertrophic scar fibroblast activation. It was observed that in the presence of iPSC­CM, the level of collagen I was markedly reduced and α­smooth muscle actin, a marker for myofibroblasts (activated fibroblasts that mediate mechanical force­induced HS formation), exhibited a significantly lower level of expression in human dermal fibroblasts (HDFs) activated with transforming growth factor­ß1. Additionally, iPSC­CM attenuated the local inflammatory cell response by blocking the adhesion of human acute monocytic leukemia cell monocytes and fibroblasts in vitro. In addition, the contractile ability of HDFs may be reduced by iPSC­CM. These observations suggest that iPSC­CM may protect against processes leading to hypertrophic scarring by attenuating fibroblast activation, blocking inflammatory cell recruitment and adhesion and reducing the contractile ability of fibroblasts.

A novel Pd-catalyzed N-dealkylative carbonylation of tertiary amines for the preparation of amides.

A novel and convenient protocol for the formation of amides via palladium-catalyzed N-dealkylative carbonylation of alkyl tertiary amines has been developed. In the presence of PdCl2(PhCN)2, CuO, PhCN and CO, a range of substituents on both aryl iodides and alkyl tertiary amines were compatible with the reaction to afford a series of N,N-disubstituted amides in moderate to excellent yields.

Oxidative tandem nitrosation/cyclization of N-aryl enamines with nitromethane toward 3-(trifluoromethyl)quinoxalines.

A novel one-pot strategy for the synthesis of 3-trifluoromethylquinoxalines from N-aryl enamines and nitromethane was developed. The tandem reaction is achieved through nitrosation of alkenes, tautomerization and cyclization, which can be applicable to a wide range of enamines with excellent functional group tolerance and afford quinoxalines in moderate to good yields.

Muscular tubes of urethra engineered from adipose-derived stem cells and polyglycolic acid mesh in a bioreactor.

We have explored the feasibility of using adipose-derived stem cells (ADSCs) and polyglycolic acid (PGA) for constructing muscular tubes of urethra in a bioreactor. With the induction of by 5-azacytidine, ADSCs were found to acquire a myoblast phenotype. Here we seeded ADSCs in a PGA mesh to construct the cell-PGA complex that was cultured statically for 1 week. Afterwards, the cell-PGA complex was subjected to extension stimulation in a bioreactor for 5 weeks. A muscular tube of urethra was formed after 6 weeks. Histological examination showed differentiated ADSCs and collagenous fibers had orientated well. This study demonstrates that tissue engineering of urethra tissues in vitro by using a bioreactor leads to tissue maturation and the differentiation of ADSCs. This novel technique could provide an effective approach for urethra tissue engineering.

The effect of mechanical extension stimulation combined with epithelial cell sorting on outcomes of implanted tissue-engineered muscular urethras.

Urethral defects are common and frequent disorders and are difficult to treat. Simple natural or synthetic materials do not provide a satisfactory curative solution for long urethral defects, and urethroplasty with large areas of autologous tissues is limited and might interfere with wound healing. In this study, adipose-derived stem cells were used. These cells can be derived from a wide range of sources, have extensive expansion capability, and were combined with oral mucosal epithelial cells to solve the problem of finding seeding cell sources for producing the tissue-engineered urethras. We also used the synthetic biodegradable polymer poly-glycolic acid (PGA) as a scaffold material to overcome issues such as potential pathogen infections derived from natural materials (such as de-vascular stents or animal-derived collagen) and differing diameters. Furthermore, we used a bioreactor to construct a tissue-engineered epithelial-muscular lumen with a double-layer structure (the epithelial lining and the muscle layer). Through these steps, we used an epithelial-muscular lumen built in vitro to repair defects in a canine urethral defect model (1 cm). Canine urethral reconstruction was successfully achieved based on image analysis and histological techniques at different time points. This study provides a basis for the clinical application of tissue engineering of an epithelial-muscular lumen.

Lumican Accelerates Wound Healing by Enhancing α2ß1 Integrin-Mediated Fibroblast Contractility.

Lumican is a dermatan sulfate proteoglycan highly expressed in connective tissue and has the ability to regulate collagen fibril assembly. Previous studies have shown that lumican is involved in wound healing, but the precise effects of lumican on reepithelialization and wound contraction, the two pivotal aspects of skin wound healing, have not been investigated. Here we explored the roles of lumican in fibroblast contractility, a main aspect of skin wound healing, by adopting mice skin wound healing model and the corresponding in vitro cellular experiments. Our results showed that lumican can promote skin wound healing by facilitating wound fibroblast activation and contraction but not by promoting keratinocyte proliferation and migration. Silencing of integrin α2 completely abolished the pro-contractility of lumican, indicating lumican enhances fibroblast contractility via integrin α2. Our study for the first time demonstrated that lumican can affect fibroblast's mechanical property, which is pivotal for many important pathological processes, such as wound healing, fibrosis, and tumor development, suggesting that lumican might have a potential to be used to modulate these processes.

An effective treatment for penile strangulation.

The aim of this study was to present our experience of patients with penile strangulation. The clinical data of 6 patients (mean age, 36 years; range, 18-72 years) with penile strangulation caused by a metal hoop are provided, where the duration of strangulation was between 3 h and 1 month. Among these patients, the case of a 22-year-old patient with a steel hoop entrapment on his penis for 5 days is described; due to serious injury of the skin at the root of penis, an intermediate split­thickness thigh skin graft was used to repair the skin loss. A review of the literature is also provided in this study, and current treatment options and outcomes are evaluated. In all the cases described, the metal hoops were successfully removed, without gangrene of the penis. These patients were discharged 2-27 days later with a satisfactory outcome. Penile strangulation is an unusual clinical condition and the consequences may be severe. The choice of method for removal depends on the type and size of metal hoop, incarceration time, trauma grade and availability of equipment. Early treatment is essential to avoid potential complications, including ischemic necrosis and autoamputation.

Synthesis of 6-(trifluoromethyl)phenanthridines via palladium-catalyzed tandem Suzuki/C-H arylation reactions.

A palladium-catalyzed tandem Suzuki/C-H arylation reaction of N-aryltrifluoroacetimidoyl chlorides with arylboronic acids has been developed. A variety of 6-(trifluoromethyl)phenanthridines were prepared in moderate to excellent yields from N-(2-bromophenyl)trifluoroacetimidoyl chlorides which can be conveniently prepared from 2-bromoaniline derivatives.

Palladium and copper cocatalyzed tandem N-H/C-H Bond functionalization: synthesis of CF3-containing indolo- and pyrrolo[2,1-a]isoquinolines.

A palladium- and copper-catalyzed tandem N-H/C-H bond functionalization reaction of ortho-(2-chlorovinyl)bromobenzenes with indoles and pyrroles has been developed. A variety of CF(3)-containing indolo- and pyrrolo[2,1-a]isoquinolines were prepared in moderate to good yields via the cyclization of 1-bromo-2-(2-chloro-3,3,3-trifluoroprop-1-enyl)benzenes with indoles and pyrroles.

CuI/TMEDA-catalyzed annulation of 2-bromo alkynylbenzenes with Na2S: synthesis of benzo[b]thiophenes.

A copper-catalyzed thiolation annulation reaction of 2-bromo alkynylbenzenes with sodium sulfide has been developed. In the presence of CuI and TMEDA, a variety of 2-substituted benzo[b]thiophenes were readily prepared in moderate to good yields by the reaction of 2-bromo alkynylbenzenes and Na(2)S·9H(2)O.

Palladium-catalyzed oxidative coupling of trialkylamines with aryl iodides leading to alkyl aryl ketones.

A new, simple method for selectively synthesizing alkyl aryl ketones has been developed by palladium-catalyzed oxidative coupling of trialkylamines with aryl iodides. In the presence of PdCl(2)(MeCN)(2), TBAB, and ZnO, a variety of aryl iodides underwent an oxidative coupling reaction with tertiary amines and water to afford the corresponding alkyl aryl ketones in moderate to excellent yields. It is noteworthy that this method is the first example of using trialkylamines as the carbonyl sources for constructing alkyl aryl ketone skeletons.

Palladium-catalyzed selective heck-type diarylation of allylic esters with aryl halides involving a ß-OAc elimination process.

Palladium-catalyzed selective Heck-type diarylation of allylic esters with aryl halides has been developed. Allylic esters are reacted with aryl iodides to provide the corresponding 1,3-diaryl propenes through a ß-OAc elimination process. It is noteworthy that the methodology can be applied in constructing the indole and benzofuran skeletons.

Myoblasts differentiated from adipose-derived stem cells to treat stress urinary incontinence.

OBJECTIVES: To investigate the application of adipose-derived stem cell (ADSC) technology in the treatment of stress incontinence. METHODS: The vaginal balloon dilatation method was used to establish an animal model of stress incontinence (in 20 female Sprague-Dawley rats), which was further examined by urodynamics and histology. Endogenous rat ADSCs were collected and induced into myoblasts with 5-Aza induction technology in vitro. The identity of myoblasts was confirmed through immunofluorescence labeling with desmin and myosin. Induced cells were injected into the posterior urethral muscularis in the bladder neck of animals with stress incontinence. The effects were examined after 1 and 3 months by urodynamics and histology. Untreated ADSCs were also implanted as a method of control. RESULTS: Both maximal bladder capacity and leak point pressure significantly increased after 1 and 3 months postimplantation, compared with the control (P <.05). Increased thickness of inferior muscularis in urethral mucosa and a greater number of large longitudinal muscle bundles were observed. Increased numbers of myoblasts appeared under the mucosa, as demonstrated by the immunochemistry analysis of alpha-smooth actin. CONCLUSIONS: ADSCs have the ability of differentiating into multiple lineages, including myoblasts. This ability to induce myoblasts can be used to treat stress incontinence, with the advantages of minimal invasion and faster recovery.