Cell-penetrating peptides (CPPs), also known as protein transduction domains, are a class of diverse peptides with 5-30 amino acids. CPPs are divided into cationic, amphipathic and hydrophobic CPPs. They are able to carry small molecules, plasmid DNA, small interfering RNA, proteins, viruses, imaging agents and other various nanoparticles across the cellular membrane, resulting in internalization of the intact cargos. However, the mechanisms of CPP internalization remain to be elucidated. Recently, CPPs have received considerable attention due to their high transduction efficiency and low cytotoxicity. These peptides have a significant potential for diagnostic and therapeutic applications, such as delivery of fluorescent or radioactive compounds for imaging, delivery of peptides and proteins for therapeutic application, and delivery of molecules into induced pluripotent stem cells for directing differentiation. The present study reviews the classifications and transduction mechanisms of CPPs, as well as their potential applications.

BackgroundLiver cirrhosis is a potentially life-threatening disease caused by progressive displacement of functional hepatocytes by fibrous tissue. The underlying fibrosis is often driven by chronic infection with hepatitis B virus (HBV). Matrix metalloproteinases including MMP-8 are crucial for excess collagen degradation. In a rat model of liver cirrhosis, MMP-8 delivery by an adenovirus (Ad) vector achieved significant amelioration of fibrosis but application of Ad vectors in humans is subject to various issues, including a lack of intrinsic liver specificity.MethodsHBV is highly liver-specific and its principal suitability as liver-specific gene transfer vector is established. HBV vectors have a limited insertion capacity and are replication-defective. Conversely, in an HBV infected cell vector replication may be rescued in trans by the resident virus, allowing conditional vector amplification and spreading. Capitalizing on a resident pathogen to help in its elimination and/or in treating its pathogenic consequences would provide a novel strategy. However, resident HBV may also reduce susceptibility to HBV vector superinfection. Thus a size-compatible truncated MMP-8 (tMMP8) gene was cloned into an HBV vector which was then used to generate a chimeric Ad-HBV shuttle vector that is not subject to superinfection exclusion. Rats with thioacetamide-induced liver cirrhosis were injected with the chimera to evaluate therapeutic efficacy.ResultsOur data demonstrate that infectious HBV vector particles can be obtained via trans-complementation by wild-type virus, and that the tMMP8 HBV vector can efficiently be shuttled by an Ad vector into cirrhotic rat livers. There it exerted a comparable beneficial effect on fibrosis and hepatocyte proliferation markers as a conventional full-length MMP-8Ad vector.ConclusionsThough the rat cirrhosis model does not allow assessing in vivo HBV vector amplification these results advocate the further development of Ad-HBV vectors for liver-specific gene therapy, including and perhaps particularly for HBV-related disease.

Liver fibrosis is an aberrant wound-healing process to chronic hepatic inflammation and is characterized by excessive accumulation of extracellular matrix (ECM) that is produced by activated hepatic stellate cells (HSCs). Thus, activated HSCs play a key role in the pathogenesis of liver fibrosis and are a potential target for the treatment of liver fibrosis. Herein, we report that a specific HSC-penetrating peptide reduced collagen accumulation by inducing the apoptosis of HSC-T6 cells. We first screened HSC-specific transduction peptides and identified a novel HSC-targeted cell-penetrating peptide (HTP) that specifically interacted with HSC-T6 cells. A chimeric peptide termed HTPK25 was consequently generated by coupling HTP with the antimicrobial peptide KLA, which is capable of initiating cell apoptosis in mammalian cells. HTPK25 entered cells in a dose-dependent manner, reduced the cell viability and induced apoptosis via the caspase 3 pathway in HSC-T6 cells. Furthermore, HTPK25 inhibited the α-smooth muscle actin and collagen I expression in HSC-T6 cells. Our results demonstrated that the HTP was able to specifically and efficiently deliver the KLA peptide into HSC-T6 cells to induce apoptosis, indicating that HTP-delivered functional agents may present a promising approach for liver fibrosis therapy.

Background: Acupuncture might be an effective intervention for treating premenstrual pain syndrome (PMS). Objective: The aim of this review was to investigate various acupuncture methods and analyze treatment characteristics for future research studies. Search Strategy: A specified literature search was performed in MEDLINE Ò (2001-2011) and the China National Knowledge Infrastructure (1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011). The key word searches combined premenstrual syndromerelated, menstrual-related, and acupuncture-related terms. Results: Twelve studies were found that met the criteria. Eleven of the trials focused on observing the treatment effect of acupuncture on PMS, while one trial focused on the relationship between pain sensitivity at acupoints and the severity of PMS. Nine studies applied body acupuncture and one used scalp acupuncture, and one used auricular acupuncture. Three studies lacked controls. The results of eight studies showed that acupuncture groups had better therapeutic effects than those in control groups. Conclusions: There were some specific acupuncture-treatment characteristics for PMS, point selection, syndrome differentiation, and timing of interventions. Further, well-designed, PMS, acupuncture clinical trials, which include the specific characteristics are needed.

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