Baiyu Zhong

Study of the biological function and penetration pathways of the mouse epidermal growth factor ethosomal delivery system

Abstract:  Biological agents are becoming increasingly popular for therapeutic applications in epidermal diseases. Ethosomes facilitate the transdermal/topical delivery of biological macromolecules. The mouse epidermal growth factor (mEGF) was selected as the model biological agent. The aim of this experiment was to determine the penetration pathways and biological functions of the mEGF ethosomal delivery system after its topical application. The mEGF ethosomal delivery system was topically applied on the dorsal skin of C57BL/6 mice at different time points. Freshly excised skin samples were obtained by skin biopsies and shock‐frozen, and immunofluorescence was performed. The results showed that penetration of mEGF ethosomes was mainly through the pilosebaceous unit and partly through the intercellular domain. Biological agents encapsulated in the ethosomal delivery system could reach each site of the pilosebaceous unit. We also found that mEGF ethosomes had caused successful transition of the hair follicles from the telogen to the anagen phase of the hair cycle.

Downregulation of TNIP1 Expression Leads to Increased Proliferation of Human Keratinocytes and Severer Psoriasis-Like Conditions in an Imiquimod-Induced Mouse Model of Dermatitis

Psoriasis is a chronic, inflammatory skin disease involving both environmental and genetic factors. According to genome-wide association studies (GWAS), the TNIP1 gene, which encodes the TNF-α–induced protein 3-interacting protein 1 (TNIP1), is strongly linked to the susceptibility of psoriasis. TNIP1 is a widely expressed ubiquitin sensor that binds to the ubiquitin-editing protein A20 and restricts TNF- and TLR-induced signals. In our study, TNIP1 expression decreased in specimens of epidermis affected by psoriasis. Based on previous studies suggesting a role for TNIP1 in modulating cancer cell growth, we investigated its role in keratinocyte proliferation, which is clearly abnormal in psoriasis. To mimic the downregulation or upregulation of TNIP1 in HaCaT cells and primary human keratinocytes (PHKs), we used a TNIP1 specific small interfering hairpin RNA (TNIP1 shRNA) lentiviral vector or a recombinant TNIP1 (rTNIP1) lentiviral vector, respectively. Blocking TNIP1 expression increased keratinocyte proliferation, while overexpression of TNIP1 decreased keratinocyte proliferation. Furthermore, we showed that TNIP1 signaling might involve extracellular signal-regulated kinase1/2 (Erk1/2) and CCAAT/enhancer-binding protein β (C/EBPβ) activity. Intradermal injection of TNIP1 shRNA in BALB/c mice led to exaggerated psoriatic conditions in imiquimod (IMQ)-induced psoriasis-like dermatitis. These findings indicate that TNIP1 has a protective role in psoriasis and therefore could be a promising therapeutic target.

Single-nucleotide Polymorphism and Haplotypes of TNIP1 Associated with Systemic Lupus Erythematosus in a Chinese Han Population

Objective. To determine the association of systemic lupus erythematosus (SLE) with single-nucleotide polymorphisms (SNP) in the TNIP1 gene and compare the expression of this gene in cases and controls from a Chinese Han population in this replication study. Methods. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry was used to genotype 19 SNP in TNIP1 in Chinese Han patients with SLE (n = 341) and controls (n = 356). Genotypes were analyzed by codominant, dominant, and recessive models. Analysis of allele frequencies and linkage disequilibrium was also performed. Western blotting and qRT-PCR were used to measure the expression of these genes in peripheral blood mononuclear cells of SLE cases and controls. Results. Seven SNP loci were significantly associated with SLE in our population (p < 0.05 for all comparisons). Two TNIP1 gene haplotypes (ATTGCGC and GTCCTAT) were associated with SLE (p = 0.0246 and p = 0.0024, respectively). Western blotting and qRT-PCR results provide evidence that patients with SLE had significantly reduced expression of TNIP1/ABIN-1 relative to controls. Conclusion. Analysis of SNP in the TNIP1 gene and expression of this gene in peripheral blood lymphocytes indicated these SNP were associated with the occurrence of SLE in Han Chinese patients. Future studies should examine the roles of these SNP in the pathogenesis of SLE.

Neutrophil elastase promotes proliferation of HaCaT cell line and transwell psoriasis organ culture model.

Background  Neutrophil elastase (NE) plays an important role in psoriasis. In this study we observed the effect of NE on the proliferation of HaCaT cells and transwell psoriasis organ culture model and investigated the mechanism.

Pharmacology and therapeutics: Neutrophil elastase promotes proliferation of HaCaT cell line and transwell psoriasis organ culture model

Background  Neutrophil elastase (NE) plays an important role in psoriasis. In this study we observed the effect of NE on the proliferation of HaCaT cells and transwell psoriasis organ culture model and investigated the mechanism.

HPV16E7 tumor antigen modified by KDEL sequence induce specific cytotoxic T lymphocytes-dependent antitumor immunity

BACKGROUND Infection by high-risk HPV (human papillomavirus) is the primary cause of cervical cancer. Dendritic cell-based (DC-based) therapeutic vaccine represents a promising approach to the prevention and treatment of many cancers, including HPV-related cancers, but current strategies have met with only limited success in preclinical and clinical research. It is necessary to find a properly and effective antigen presenting system of DC-based vaccine. OBJECTIVE To design a new HPV16 therapeutic vaccine using an endoplasmic reticulum (ER) retrieval signal and study its ability to induce the specific CTL activity in vitro and in vivo. METHODS E7(p)-KDEL and its control peptide were synthesized on solid phase. A series of methods were used, including standard (51)Cr-labeled release assay, enzyme-linked immunospot (ELISPOT) assay and ELISA, to detect the CTL activity induced by different peptides. Prophylactic models and therapeutic models were examined to detect the in vivo effectiveness of E7(p)-KDEL-loaded DCs. RESULTS The specific CTL activity induced by E7(p)-KDEL-loaded DCs was much stronger than that induced by the other peptide-loaded DCs. Comparing with the control peptides, after incubation with the spleen cells of mice, the E7(p)-KDEL-loaded DCs could induce higher concentration of secreted IFN-gamma and had higher ELISPOT numbers. In animal models, E7(p)-KDEL-loaded DCs vaccines effectively protected mice against fatal TC-1 tumor challenge and cured tumor-bearing mice. CONCLUSIONS The ER retrieval signal-mediated antigen delivery system may have important clinical application for cancer therapy, even virus infectious disease and autoimmune disease.

The umbilical polyp: a report of two cases and literature review

A 17-year-old girl presented with an unusual protuberant appearance of the umbilicus since birth. This lesion produced serous discharge that sometimes stuck to her clothes. The patient had been seen in early childhood, but had not received any therapy. Physical examination showed a 0.5 × 0.5-cm, well-defined, rounded, polypoid lesion in the umbilicus. This lesion was red and moist, and produced serous secretions (Fig. 1). The hair, nails, and mucous membranes of the patient were normal. Systemic examination revealed no other abnormalities. The preand postnatal history of the patient were unremarkable, and there was no family history of congenital anomalies. A review of the patient’s laboratory investigations showed normal blood cell counts, liver function tests, and serum electrolytes. A radiograph of the abdomen was normal. Because of these unusual features, a biopsy of the lesion was

Congenital localized basaloid follicular hamartoma: a case report and review of the literature

Basaloid follicular hamartoma (BFH) is a rare benign follicular hamartoma, with variable clinical features. Histopathologically, it is likely to be confused with basal cell carcinoma (BCC). BFH may be present alone or along with hereditary skin diseases, such as Bazex-DupreChristol syndrome, Brown-Crounse syndrome, myasthenia gravis, alopecia, and systemic lupus erythematosus. Here we report a case of congenital localized BFH.

Multiple eccrine spiradenomas in a linear or zosteriform distribution involving the right side of the body

A 23-year-old woman presented with asymptomatic papulonodular lesions on the right side of the body of 10 years’ duration. The lesions initially began as a few small, asymptomatic, mauve maculae and papules clustering on the right forearm 10 years earlier. The lesions increased in number and extent to affect the right side of the chest and back, and right leg. Over the last 7 years, soft intradermal nodules of increasing size have appeared. The primary diagnosis in the outpatient clinic was “angioma.” The patient was well and had no significant past medical or family history. On physical examination, there were small, mauve, macular and papular lesions on the right side of the trunk varying in size from 2 to 5 mm. Some papules were fused into large groups. The lesions were distributed in a linear or zosteriform pattern along the nervus intercostalis and the longitudinal axis of the extremities, respectively. The lesions were firm, nontender, and fixed to the skin. There were some soft, nontender, intradermal nodules of 3 to 6 mm in diameter. Two additional nodules on the right forearm and right ventral surface were about 15 mm in diameter, without adhesions to the epithelium; the overlying skin was light blue (Fig. 1a,b). There were no similar lesions on the left side of the body. Biopsies taken from a papule on the right abdomen and the large nodule on the right forearm both revealed a multilobulated tumor mass surrounded by a capsule of connective tissue. The lobules were composed of two types of tumor cell: small basophilic cells and relatively large pale cells with vesicular and ovoid nuclei. The former were arranged along the periphery of the tumor masses, whereas the latter were located towards the center of the masses. Some tumor cells were arranged in characteristic small rosettes. A few ducts of cystic spaces were found (Fig. 2a,b). These features were characteristic of eccrine spiradenoma. Laboratory studies showed normal values for total blood count, urinalysis, liver and renal function tests, and erythrocyte sedimentation rate. The clinical and histologic findings were consistent with eccrine spiradenoma. As the lesions were too extensive to excise, it was decided that the larger nodules should be surgically excised in stages.

Four new cases of stiff skin syndrome with unusual presentations

Editor, Stiff skin syndrome (SSS) is a rare cutaneous connective tissue disorder which is highly heterogeneous and has distinct variants. Although SSS is characterized by stone-hard indurations and thickening of the skin and subcutaneous tissues and is accompanied by limited joint mobility and mild hypertrichosis, the phenotypes of SSS may be variable and sometimes unexpected. Herein we report four cases of SSS with unusual clinical presentations, including bilateral involvement, hernial sac-like changes, concomitant herpes zoster and low levels of immunoglobulins. The first case was a 20-year-old man who presented with a 17-year history of extensive muscle rigidity and limited joint mobility. Physical examination showed that the skin on the waist and joints of all four limbs was indurated and resistant to extension when pulled up in a pinch. On the lumbar area, there were brown plaques with clear boundaries. Hypertrichosis was noted