In view of the anatomical and physiological barrier of the ocular surface and the intraocular structure, the conventional ophthalmic agents cannot efficiently reach the lesion site.Currently, the different types of nanomaterials possess great advantages in delivering drugs due to their characteristics of small size, easy preparation, degradability, strong targeting and less irritation to biological tissue.As drug delivery carriers, nanomaterials have been widely used in ocular drug delivery so as to treat different types of eye diseases.In this paper, the applications of nanomaterials as drug delivery carriers in treating eye diseases are briefly reviewed.

OBJECTIVETo observe the effect of Wenyang Huazhuo Tongluo Recipe (WYHZTLR) on the proportion of T helper 17 cells (Thl7)/regulatory T cells (Treg), and serum levels of IL-17 and IL-10 in peripheral blood of systemic sclerosis (SSc) patients with yang qi insufficiency and turbidity induced collaterals blockage syndrome (YQITICBS).

METHODSTotally 82 SSc patients were randomly assigned to the Western medicine group (as the control group) and the integrated Chinese and Western medicine group (as the treatment group), 41 cases in each group. All patients took methotrexate (MTX) tablet and prednisone tablet. Patients in the treatment group additionally took WYHZTLR. The treatment course for all was six consecutive months. Besides, another 70 healthy volunteers were recruited as a healthy control group (as the healthy group). Percentages of Th17 and Treg in peripheral blood were detected by flow cytometry. Serum levels of IL-17, IL-10, von Willebrand factor (vWF), aminoterminal propeptide of type l procollagen (PIIINP), and cross-linked carboxyterminal telopeptide of type I collagen ( I CTP) were measured by double antibody sandwich ELISA. The correlations between Th17/Treg and levels of vWF, PIIINP, I CTP, skin score, and disease activity index were observed by Pearson correlation analysis.

RESULTSThe percentage of Th17 in peripheral blood, ratios of Th17/Treg, and the serum level of IL-17 were significantly higher, but the percentage of Treg and the serum level of IL-10 were significantly lower in SSc patients, when compared with those of the healthy group (P <0. 05, P <0. 01). Compared with the same group before treatment, the percentage of Thl7, ratios of Thl7/Treg, and levels of IL-17, vWF, and PIIINP all decreased in the two groups after treatment (P <0.05, P <0.01), but the percentage of Treg and the IL-10 level increased (P <0. 05, P <0. 01). Meanwhile,the level of I CTP was higher in the treatment group after treatment (P <0. 05). The improvement of all indices except the percentage of Th17 was more obvious in the treatment group than in the control group (P <0. 05, P <0. 01). The ratio of Th17/Treg was positively correlated with levels of vWF, PIIINP, skin score, and disease activity index before and after treatment respectively (P <0. 01), but with no obvious correlation with the level of I CTP (P >0. 05).

CONCLUSIONWYHZTLR could achieve its therapeutic effect on SSc patients by regulating Th17/Treg imbalance, lowering levels of vWF and PIIINP, and elevating the level of I CTP.

Drugs, Chinese Herbal ; therapeutic use ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Humans ; Interleukin-10 ; Interleukin-17 ; Methotrexate ; Peptide Fragments ; Procollagen ; Scleroderma, Systemic ; drug therapy ; T-Lymphocytes, Regulatory ; Th17 Cells

Produced by and purified from Taxus brevifolia, Taxol (paclitaxel) has become a widely used cancer drug in clinic. Due to the rapid growing market, current industrial production of taxol by semi-synthesis that consumes large amount of Taxus trees cannot meet the requirement of the market. The discovery of taxol-producing fungus Taxomyces andeanae, an endophyte of T. brevifolia, by Stierle et al (1993), paves a new way to the production of the drug, i.e. employing large-scale fungal fermentation to make Taxol at lower cost and yet higher yield. This review discusses the present problems in taxol production in pharmaceutical industry, the finding and research progress on taxol-producing fungi, and the potential application of fungal fermentation to manufacture this important drug.
Antineoplastic Agents, Phytogenic ; biosynthesis ; Fermentation ; Mitosporic Fungi ; metabolism ; Paclitaxel ; biosynthesis ; Taxus ; microbiology ; Technology, Pharmaceutical ; methods

Objective To investigate the effects of Longdan Xiegan Decoction on the expression of Notch signaling-related genes in rats with experimental autoimmune uveitis (EAU).Methods Totally 24 Lewis rats were randomly divided into normal control group,EAU model group and Longdan Xiegan Decoction treatment group.A rat model of EAU was established in the EAU model group and Longdan Xiegan Decoction treatment group,followed by intragastrical administration of Longdan Xiegan Decoction in the latter group after successful modeling.On day 12 after different treatments,the spleen and lymph nodes were isolated from rats of all the three groups for the collection of CD4 + T ceils,and the levels of both Th17 and Treg cells were analyzed by flow cytometry to calculate the ratio of Th17 to Treg cells.Meanwhile the levels of Notch1,Notch2,Notch3,Notch4 mRNAs expression were monitored by qRT-PCR.Moreover,the expressions of Notch signaling-related proteins were further detected using ELISA technique.Results Flow cytometry showed increased Th17 cell level but decreased Treg cell level in the EAU model group when compared with the normal control group.However,after treatment with Longdan Xiegan Decoction,the Th17 level was decreased,whereas the Treg level was increased,and the ratio of Th17 to Treg gradually restored to equilibrium when compared to EAU model group.qRT-PCR results showed that the expression levels of Notch1,Notch2 and Notch4 mRNAs in Longdan Xiegan Decoction treatment group were significantly higher than those in the normal control group (all P ＜ 0.01),but lower than those in EAU model group on day 12 after treatment (all P ＜ 0.01),without Notch 3 expression in the spleen and lymph nodes.In addition,Notch 1,Notch 2 and Notch 4 protein levels of the spleen and lymph nodes in Longdan Xiegan Decoction treatment group showed the similar tendency as compared to those of Notch 1,Notch 2 and Notch 4 mRNAs (all P ＜ 0.01),and the expression of Notch 3 protein was still not observed.Conclusion Longdan Xiegan Decoction can effectively relieve the imbalance of Th17/Treg cells in EAU rats,and its mechanism may involve the differentiation of naive CD4+ T cells into Th17 and Treg cells,which is regulated by Notch signaling.

Objective To investigate the regulatory roles of rno-miR-30b-5p in the expression of Atg5,Atg12 and Becn1 autophagy genes and their expressions in rats with experimental autoimmune uveitis (EAU).Methods Application of dual luciferase report system was conducted to detect the regulatory roles of rno-miR-30b-5p in Atg5,Atg12 and Becn1 gene expression.Lewis rats were randomly divided into control group and EAU group,with 6 rats in each group.Next,rats in EAU group were immunized to establish EAU model.After treatments,Genesis-D fundus camera was used to observe the fundus inflammation every day.After immunization for 12 days,the pathological features of rat ciliary body and retina were detected,and meanwhile,the spleen and lymph nodes in both groups were isolated to detect the expressions of rno-miR-30b-5p,Atg5,Atg12 and Becn1 genes by quantitative PCR (Q-PCR);the levels of autophagy related proteins were determined by ELISA.Results Dual luciferase report gene expression assay confirmed that Atg5,Atg12 and Becn1 were target genes of rno-miR-30b-5p.Twelve days after immunization,compared with the control group,rats in the EAU group had severe iris adhesions and severe blood vessel swelling,and pathological examination revealed massive infiltration of inflammatory cells in the ciliary body and retina.Furthermore,rno-miR-30b-5p mRNA was 0.46 ±0.01,0.29 ±0.17in the spleen and lymph nodes in EAU group,respectively,which was down-regulated when compared with the control group (P ＜0.01);whereas the expressions of Atg5,Atg12 and Becn1 were significantly upregulated,and the differences were statistically significant (all P ＜ 0.05).ELISA results showed that Atg5,Atg 12 and Becn 1 protein expression levels in the spleen and lymph nodes in EAU rats were significantly higher than those in the control group (all P ＜ 0.05).Conclusion rno-miR-30b-5p can regulate the expressions of Atg5,Atg12 and Becn1 autophagy-related genes.The down-regulation of rno-miR-30b-5p expression in the spleen and lymph nodes in EAU rats can significantly up-regulate the expressions of Atg5,Atg12 and Becn1 genes,thereby regulating the pathogenesis of uveitis.

OBJECTIVETo observe the histological and ultrastructural changes of the skin and hair follicles following hair removal by alexandrite laser in Tibet mini-pigs.

METHODSTwelve healthy Tibet mini-pigs with dark hair were treated with alexandrite laser for hair removal. The skin specimens were taken immediately and at 1 h and 1, 3, 5, 10, 15, 30, 60 days after the laser treatment for observation under optical and transmission electron microscope.

RESULTSLaser hair removal resulted in extensive coagulation necrosis, carbonization and falling of the subcutaneous hair shafts, and some of the cells in the outer root sheath and hair bulb underwent degenerative and necrotic changes. One hour after laser treatment, the cells in the outer root sheath and bulb exhibited nuclear condensation, fragmentation and or karyolysis characteristic of cell apoptosis. The cell apoptosis reached the peak level on day 3 after the laser exposure, accompanied by endothelial degeneration in the hair papilla vessels, edema and lymphocyte infiltration in the dermal tissues. Tissue reaction and inflammation were relieved on day 5, and the dermal tissue and follicles recovered their normal structures on day 10. At 60 days after the treatment, the hair follicles decreased markedly but the structure of the residue follicles remained normal.

CONCLUSIONAlexandrite laser exposure results in selective destruction of the follicles by inducing direct coagulation and cell apoptosis to achieve permanent hair removal. Tibet mini-pigs with black hair can be used as the animal model of clinical laser hair removal.

Animals ; Hair Follicle ; radiation effects ; ultrastructure ; Hair Removal ; methods ; Lasers, Solid-State ; therapeutic use ; Microscopy, Electron, Transmission ; Swine ; Tibet

OBJECTIVEA 12 mer phage display peptide library was used to identify hepatitis A virus mimotopes of antigenic determinants, to provide the feasibility of virus epitope mapping by using this approach.

METHODSUsing purified anti-hepatitis A virus monoclonal antibody as affinity selective molecule, phage display peptide library was biopanned and positive clones were selected by ELISA, competition assay and DNA sequencing.

RESULTS10 ELISA positive clones were chosen for DNA sequencing, and the displayed peptide sequences were deduced. 9 of them showed identical nucleotide sequence, and similarity in their amino acid sequence with VP1 of HAV HM175 was found, but no sequence homology was found between the other phage clone and the capsid proteins of HAV. Those peptides may behave as mimotopes of HAV.

CONCLUSIONThe mimotope of HAV was selected by using phage display peptide library screening. The results provide the potential of this method to search for the mimotopes of the virus.

Amino Acid Sequence ; Antigens, Viral ; chemistry ; genetics ; immunology ; Epitope Mapping ; Epitopes ; Hepatitis A ; virology ; Hepatitis A virus ; chemistry ; genetics ; immunology ; Humans ; Molecular Sequence Data ; Peptide Library

OBJECTIVETo construct full-length hepatitis B core particles presenting preS1 aa 21-47 epitope and truncated core particles presenting preS1 aa 37-45 epitope on their surface and compare their antigenicity.

METHODSPreS1 aa21-47 epitope and aa 37-45 epitope were inserted respectively into full-length hepatitis B core (aa 1-183) and truncated HBcAg (aa 1-144), between the 78th (Asp) and 79th (Pro). The genes synthesized after the codon optimization were ligated to the pET43. 1a vector with the same cohesive terminal (NdeI and XhoI) and expressed in the E. coli expression system. The morphology of the proteins of interest were observed by electron microscope and characterized by ELISA and Western Blotting.

RESULTSThe morphology of the virus-like particles were confirmed by electron microscope. H2 were solid particles with a diameter of (31.61 +/- 1.27) nm, while H3 were hollow particles with a diameter of (28.46 +/- 1.16) nm. Statistical analysis showed that H2 is larger than H3 in the diameter (P < 0.01). The antigenicity of the inserted epitopes and carrier protein were identified by ELISA and Western Blotting.

CONCLUSIONChimeric hepatitis B core particles presenting the preS1 neutralizing epitopes on their surface have been expressed, purified and identified, which lays the foundation for its application in vaccine research.

Epitopes ; chemistry ; genetics ; immunology ; Hepatitis B ; immunology ; virology ; Hepatitis B Core Antigens ; chemistry ; genetics ; immunology ; Hepatitis B Surface Antigens ; chemistry ; genetics ; immunology ; Hepatitis B virus ; chemistry ; genetics ; immunology ; Humans ; Neutralization Tests ; Protein Precursors ; chemistry ; genetics ; immunology ; Recombinant Fusion Proteins ; chemistry ; genetics ; immunology

OBJECTIVETo evaluate the clinical efficacy of syndrome differentiation-based treatment with traditional Chinese medicine (TCM) versus losartan therapy in addition to basic treatment for management of proteinuria in patients with chronic kidney disease.

METHODSThis multicenter, randomized, and case-controlled clinical trial was conducted among 81 consecutive patients meeting the inclusion criteria. The patients were randomized consecutively to receive TCM treatments according to the syndrome patterns in TCM (spleen and kidney Qi and Yin deficiency, and spleen and kidney Qi and Yang deficiency, n=60) or oral losartan therapy (50 mg/day, n=21) in addition to the basic treatments. All the patients were followed up for 24 weeks to observe the clinical effects.

RESULTSThe patients in TCM group showed a significantly higher overall response rate (93.33%) than those in losartan group (76.20%, P<0.05). The TCM score in the two groups were all decreased at week 24 as compared with baseline (P<0.01 or P<0.05). The TCM scores in both groups decreased significantly after the treatments as compared with the baseline scores (P<0.05). After a 8-week-long treatment, Scr, eGFR and Cys-C, U-Pro/24 h, and MA/Cr all decreased significantly in TCM group (P<0.05) but showed no significant changes in losartan group (P>0.05).

CONCLUSIONSyndrome differentiation-based TCM treatment in addition to basic treatments can produce satisfactory therapeutic effects on proteinuria in patients with chronic kidney disease by improving the clinical symptoms, reducing TCM symptom scores and proteinuria, and protecting the renal functions.

Adult ; Aged ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Losartan ; therapeutic use ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Phytotherapy ; Prospective Studies ; Proteinuria ; drug therapy ; etiology ; Renal Insufficiency, Chronic ; complications ; drug therapy

OBJECTIVETo investigate magnetic resonance imaging (MRI) features of parotid malignant tumors and study their pathological basis.

METHODSForty-seven patients with parotid malignant tumors confirmed by surgery (41 patients) or biopsy (6 patients) were enrolled in this study. A comparative analysis was conducted of the pathological and MRI findings in 30 patients with the entire lesions available. Each of the MRI features was analyzed retrospectively and the typical MRI findings of common parotid malignant tumors were summarized.

RESULTSMRI allowed accurate diagnosis of parotid malignant tumors. Four patients with low-grade mucoepidermoid carcinoma showed well-defined tumor margin and were difficult to distinguish from benign tumors. Six patients with high-grade mucoepidermoid carcinoma had obscure margin of the tumor which easily underwent necrosis with liable lymph node involvement. The 8 cases of adenoid cystic carcinoma was characterized by extensive invasion surrounding the parotid gland. Most of 8 cases of malignant pleomorphic adenoma still showed high and heterogeneous signal on T2WI, with irregular shape and poorly defined margin. Nine cases of lymphoma all had secondary lesions characterized by extensive involvement and presence of multiple nodules. The 4 cases of acinic cell carcinoma showed either regular or irregular tumor morphology, presenting with high signal intensity on T1WI and T(2)WI.

CONCLUSIONMRI is an important modality for the diagnosis of parotid malignant tumors. Most of the common parotid malignant tumors have characteristic MRI and pathological features, which make possible their differential diagnosis.

Adolescent ; Adult ; Aged ; Carcinoma, Adenoid Cystic ; diagnosis ; pathology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Parotid Neoplasms ; diagnosis ; pathology ; Retrospective Studies ; Young Adult