[Comparison of early postoperative effects between anterior bladder and posterior bladder approaches in robotic assisted laparoscopic radical prostatectomy].

Objective: To examine the effect of robotic assisted laparoscopic radical prostatectomy with different approaches on early postoperative effects. Methods: Totally 44 patients (average age of 65.9 years, range: 46 to 81 years) underwent robotic assisted laparoscopic radical prostatectomy by a single operator at Department of Urology, Peking Union Medical Collage Hospital from March 2018 to March 2020 were retrospectively analyzed. The mean age was 65.9 years (range: 46 to 81 years), including 24 cases in the anterior bladder approach group (anterior approach group) and 20 cases in the posterior bladder approach group (posterior approach group). The preoperative clinical data, perioperative related data and postoperative urinary control recovery were compared between the two groups by t test, χ2 test or Fisher exact test. Results: In terms of clinical data, there was no difference in age, prostate volume, preoperative prostate specific antigen and Gleason score(all P>0.05). There was no significant difference in operation time ((184±43) minutes vs. (193±42) minutes, t=-0.599, P=0.55), bleeding volume ((218±88) ml vs. (225±115) ml, t=-0.244, P=0.81), postoperative stage (T2/T3: 15/9 vs. 12/8, χ²=0.029, P=0.87) and positive rate of cutting edge (29.2% (7/24) vs. 30.0% (6/20), χ²=0.004, P=0.95). In terms of postoperative urinary control, patient rates who achieved urinary control immediately after extubation was significantly higher for the posterior approach group than the anterior approach group (30.0% (6/20) vs. 4.2% (1/24), P=0.04). There was no significant difference between two groups for those who achieved urinary control 3 months after operation (6 cases vs. 11 cases, P=0.06), 6 months after operation (20 cases vs. 19 cases, P=0.36) and those who achieved urinary control 12 months after operation (23 cases vs. 19 cases, P=1). Conclusion: For robotic assisted laparoscopic radical prostatectomy, the posterior approach does not prolong the operation time, does not increase the amount of bleeding, and improves the short-term postoperative urinary control.

[Surgery treatment of ectopic adrenocorticotrophic hormone syndrome].

OBJECTIVE: To investigation the diagnosis and treatment of ectopic adrenocorticotrophic hormone (ACTH) syndrome. METHODS: The clinical characters of 57 cases of ecotopic ACTH syndrome from Jan. 1996 to Dec. 2016 were collected and analyzed. The 57 cases included 32 males and 25 females. The age ranged from 11 to 68 years (average 32 years). ACTH levels significantly increased from 16.5 to 365.6 pmol/L, with average 77.6 pmol/L (normal range <10.1 pmol/L). The pituitary MRI did not found lesions. The CT showed that their bilateral adrenal glands diffused small nodular changes or nodular hyperplasia. The 57 cases were divided into 3 groups according to different treatment options. In the study, 25 ectopic ACTH syndrome cases (44%) were group A, without identified source of ectopic hormone, were treated with bilateral or unilateral adrenalectomy due to the severity of the disease and difficulty of operation. Group B was composed of 16 cases (28%) diagnosed as ectopic ACTH syndrome by finding ectopic ACTH tumors and surgical resection. Group C included 16 cases (28%) with nonsurgical therapy. Different treatment results and prognosis were analyzed. RESULTS: In the study, 40 cases of the 57 had been followed up for 6 months to 10 years. In group A, of the 25 cases with bilateral or unilateral adrenalectomy, 4 died of diabetes and severe pulmonary infection, 18 survived, and 3 were lost to the follow-up, and the survival rate was 81% (18/22). In group B, of the 16 cases with radical tumor resection, 5 died of tumor recurrence 0.5-6.0 years after operation, 3 survived, and 8 were lost to the follow-up, and the survival rate was 37.5% (3/8). In group C, of the 16 non-operation patients, 4 with radiotherapy and chemotherapy died of metastases, diabetes or pulmonary infection, 6 with chemotherapy died of pulmonary infection within 1 year and the others were lost to the follow-up, and the survival rate was 0. CONCLUSION: Ectopic ACTH syndrome is difficult to treat. Adrenalectomy is effective for the management of ectopic ACTH syndrome, especially for those patients with severe Cushing's syndrome, but the primary tumor can not be located.

Characteristics of cathelicidin-Bg, a novel gene expressed in the ear-side gland of Bufo gargarizans.

The traditional Chinese medicine Chan Su (toad venom) comprises dried secretions of the ear-side gland of Bufo gargarizans. Chan Su is known for its small molecular components, which include telocinobufagin, marinobufagin, and bufalin, while in other amphibians, studies mainly focus on peptide components. Until recently, no genes expressed in the ear-side gland of B. gargarizans gland had been cloned. In this study, cathelicidin-Bg, a coding sequence of anti-microbial peptide (AMP), was cloned. The predicted amino acid sequence of cathelicidin-Bg was very similar to that from other amphibians, with a 34-amino acid mature peptide predicted in the C-terminus. The functions of this mature peptide were verified by microbe and tumor cell inhibition assays. Our results showed that the mature peptide of cathelicidin-Bg could inhibit the proliferation of Staphylococcus aureus and Pseudomonas aeruginosa. The mature peptide was also shown to selectively inhibit tumor cells. These results indicate that the identified coding sequence represents an active peptide of Chan Su.

HDAC6: physiological function and its selective inhibitors for cancer treatment.

Acetylation and deacetylation of histones are important in regulating gene expression and play a key role in modification of gene transcription. Specific HDACs isoforms can be regarded as a target for cancer therapy avoiding side-effects, HDAC6 with a unique physiological function and structure has become a hot issue recently. The unique isoform HDAC6 is involved in tumorigenesis, development and metastasis through tubulin, HSP90, invasin and ubiquitin-protein. Here we review the structure elements, biological function, and recent selective inhibitors of HDAC6, and study the structure-activity and structure-selectivity relationship.

A new boronic acid-based fluorescent sensor for L-dihydroxyphenylalanine.

Catecholamines, such as dopamine and L-dihydroxyphenylalanine (L-DOPA), are associated with different physiological functions and diseases. In our recent studies, a novel water-soluble boronic acid compound 3c was identified as a selective fluorescent sensor for L-DOPA. This compound not only has the ability to interact with dopamine and catechol, but also has no fluorescence intensity change for L-DOPA precursors in vivo, such as L-tyrosine.

Expression, purification, and S-nitrosylation of recombinant histone deacetylase 8 in Escherichia coli.

Histone deacetylase (HDAC) 8 is a zinc ion dependent enzyme involved in removing the acetyl group from the core histones and other proteins which belong to Class I HDACs. It was reported that nitric oxide (NO) is a key regulator of HDAC function and S-nitrosylation of HDAC2 induces chromatin remodelling in neurons. This work reports the successful recombinant expression of human HDAC8 in Escherichia coli with two plasmids and the purification and S-nitrosylation in vitro. It was found that HDAC8 can be S-nitrosylated by the NO donor S-nitrosoglutathione (GSNO) in vitro, and the activity of HDAC8 was significantly inhibited when incubated with GSNO and S-nitrosocysteine in a time- and dosage-dependent manner, but sodium nitroprusside (SNP), and dithiothreitol cannot reverse this inhibition. These observations support and extend the concept that NO may regulate HDAC8 function by S-nitrosylation.

Design, synthesis and activity study of aminopeptidase N targeted 3-amino-2-hydroxy-4-phenyl-butanoic acid derivatives.

A series of (2RS,3S)-3-amino-2-hydroxy-4-phenyl-butanoic acids (AHPA) derivatives (MA0-MA7) were synthesized. The in vitro aminopeptidase N (APN) enzyme and cell proliferation assay of target compounds were investigated. The results showed that most compounds displayed potent inhibitory activities against APN, compound MA0 showed even better inhibitory effects than bestatin on both enzyme activity and HL60 cell proliferation. The FlexX docking result showed the mode of binding between MA0 and APN.

Design, synthesis, and primary activity evaluation of pyrrolidine derivatives as matrix metalloproteinase inhibitors.

A series of novel pyrrolidine derivatives was designed, synthesized, and assayed to determine the derivatives' activity against matrix metalloproteinase-2 (MMP-2) and aminopeptidase N (APN)/CD13. Preliminary biological tests showed that most compounds inhibit MMP-2 in a highly selective manner compared to APN. Compounds 9d, 9e, and 9g had better inhibitory activity than LY52 and could be used as lead compounds in the future.

Direct effects of fascaplysin on human umbilical vein endothelial cells attributing the anti-angiogenesis activity.

Novel anti-angiogenesis activity of fascaplysin via VEGF blockage was recently revealed by our previous study in addition to the reported cyclin-dependent kinase 4 (CDK4) selective inhibition. To uncover more details of this pharmacologically prospective property, this study further investigated whether fascaplysin had direct anti-proliferation effects on human umbilical vein endothelial cells (HUVEC), which might be contributing to anti-angiogenesis. The results showed that G1 cell cycle arrest was induced by 2.6 µM fascaplysin in a time-dependent manner, and exhibited more sensitive than hepatocarcinoma cells BeL-7402 and Hela cells. Approximately 56.09 ± 2.63% of the cells were arrested at the G1 phase after 24h, and 64.94 ± 2.07% after 36 h, comparing to the 22.82 ± 1.2% in methanol treated cells. Apoptosis of HUVEC cells was induced by 1.3 µM fascaplysin and indicated by the sub-G1, Hoechst staining, terminal deoxynucleotidyl transferase dUTP-mediated nicked end labeling (TUNEL) assay, and annexin-V and propidium (PI) label. This apoptosis response was further confirmed by the detection of active caspase-3 and by western blotting using antibodies against Bax, Bcl-2, procaspase-8, and Bid, indicating that apoptosis in HUVEC cells may involve a mitochondria pathway, by the demonstration of an increase in the Bax/Bcl-2 ratio. Together, our results suggest that the anti-angiogenesis activity of fascaplysin is through the direct effects of cell cycle arrest and apoptosis on HUVEC.

QSAR studies of histone deacetylase (HDAC) inhibitors by CoMFA, CoMSIA, and molecular docking.

In order to develop highly potent antitumor agents, three-dimensional quantitative structure-activity relationship (3-D QSAR) studies were conducted using a series of thienyl-based hydroxamic acids. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods were applied to provide the structural information for further chemical modification and optimization. ClogP was applied as an additional descriptor in the CoMFA analysis to study the effects of lipophilic parameters on the activity of these compounds, and it did improve the statistical significance of the model. Two molecules were designed based on the 3-D QSAR analysis, their activity values were predicted by the generated model, and their binding mode was elucidated by a docking approach compared to molecules in the dataset.

A microplate-based screening assay for neuraminidase inhibitors.

Neuraminidase (NA) represents a highly promising new target for drug development in influenza virus genes. Rapid screening of enzyme inhibitors is a key method for the identification of leading compounds. In order to speed up the screening for enzyme inhibitors of natural and synthetic origin, effective and fast assays are needed. 2'-(4-Methylumbelliferyl)-α-D-N-acetylneuraminic acid (4-MUNANA) was selected as substrate for development of a microplate-based assay. The enzymatic reaction conditions were optimized as follows: in a 100 µL reaction mixture, the final concentrations were 32.5 mM sodium acetate (pH 3.5), 20 µM 4-MUNANA, 0.005% (w/v) bovine serum albumin, and 0.42 µg/mL NA. In the study, the doseresponse relationship of oseltamivir carboxylate to NA activity was observed. In addition, an overall Z' value of 0.8 proved the systems robustness and potential for screening. The assay system developed will be a valuable tool to discover new structures for the therapeutic inhibition of NA used to treat Influenza.

The main functions and structural modifications of tripeptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) as a chemotactic factor.

Gram negative bacteria-derived and synthetic N-formyl peptides play a key role in host defense as chemotactic factors for phagocytic leukocytes. The first compound to be identified was N-formylmethionyl-leucyl-phenylalanine (fMLP) which contains highly potent leukocyte chemoattractant. Natural fMLP was subsequently purified and identified in supernatants of gram negative bacteria. Recently, much more attention has been focused on the human formyl peptide receptor (FPR) and its variant formyl peptide receptor-like 1 (FPRL1) and formyl peptide receptor-like 2 (FPRL2). Chemotactic factors such as fMLP interact with their specific cell surface receptors, which results in multiple biological responses through a G protein-coupled signal pathway. In this review, the functions and structural modifications of fMLP are discussed in view of future drug development.

3D-QSAR study with pharmacophore-based molecular alignment of hydroxamic acid-related phosphinates that are aminopeptidase N inhibitors.

3D-QSAR models for a series of aminopeptidase N inhibitors were developed based on comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA).GALAHAD, a pharmacophore generation module involving a genetic algorithm, was used to generate the pharmacophore model of the series of inhibitors. Molecules both in the training set and test set were aligned to the pharmacophore model. Values for the CoMFA model were r(2) = 0.992, q(2) = 0.586, SEE = 0.111, and F (8, 10) = 191.263. Values for the CoMSIA model were r(2) = 0.990, q(2) = 0.776, SEE = 0.123, and F (7, 11) = 156.68. This model can help not only in improving current understanding of enzyme-ligand interactions but also in predicting the activity of derivatives and designing new compounds with better potency.

Novel N-hydroxybenzamide histone deacetylase inhibitors as potential anti-cancer agents.

Histone deacetylases (HDACs) are a class of Zn(2+) dependent metalloproteases that play an important role in tumorigenesis. Inhibition of HDACs may be a potential strategy for cancer therapy. This study designed and synthesized a series of novel N-hydroxybenzamide histone deacetylase inhibitors based on the structural features of suberoylanilide hydroxamic acid (SAHA), the first HDAC inhibitor that came to market. Preliminary biological evaluation in vitro found that most of the inhibitors had satisfactory inhibitory activity (IC(50) =1-17 µM) against HDACs and HCT116 tumor cells.

Recent advances in P-glycoprotein-mediated multidrug resistance reversal mechanisms.

Expression of the multidrug resistance (MDR) phenotype is responsible for chemotherapy failure in numerous cancers. Overexpression of mdr1 gene-encoded permeability glycoprotein (P-gp) is known to play a pivotal role in the development of this phenotype. The role of P-gp has been proposed as an important goal in the design of chemotherapy strategies. However, modulation of P-gp activity by chemotherapy has limited possibilities because of toxicity and poor specificity. In this article, we review the latest advancements in different potential P-gp-mediated MDR reversal mechanisms as well as the methods of evaluating MDR reversal activity, which would be helpful in finding novel MDR reversal agents (or chemosensitizers).

China's new drug R&D is steadily advancing.

China appears to consistently lag behind developed countries like the US, Japan, and the nations of Europe in the development of pharmaceuticals, putting China in an embarrassing situation. In fact, China is still dependent on foreign imports for most highly effective cures to major diseases such as cancer, diabetes, hepatitis, and neurodegenerative disease. There is no denying the fact that governmental support, and especially a signifi cant amount of fi nancial support and political assistance to include government restructuring, is needed for the establishment of new drug Research and Development (R&D). Fortunately, China's authorities have recently recognized the importance of new drug development and have committed to implementing strong measures to help establish new drug R&D. This improvement in the government's status is showing immediate and substantial promise in the field of pharmaceuticals. On January 4, 2007, a research group directed by Wang Ming-Wei, Head of the National Center for Drug Screening, Shanghai Institute of Materia Medica (SIMM), made a breakthrough in the development of novel category I anti-diabetes drugs with the support of the Ministry of Science & Technology of China, the National Natural Science Foundation (NSFC) of China, and the Shanghai municipal government. Taking almost four years, the group finally developed a nonpeptide agonist of small molecule glucagon-like peptide 1 receptors with effi cacy in diabetic db/db mice (Proc Natl Acad Sci U S A 2007;104:943-948). As an antidiabetes drug, a peptide hormone traditionally had to be taken as an injection, which greatly limited its clinical application. In contrast, the new compound can be taken orally. This offers hope for the development of a new field of peptidomimetics for orally-available nonpeptide small molecules. Today, the ever-growing prevalence of major diseases worldwide is driving growth in new drug spending, encouraging the marketing of newly developed and effi cacious therapies. This achievement appears to have significantly boosted the field of new drug research in China. While "China's pharmaceutical firms lag far behind [their Western counterparts] in terms of biological preparations" "today's achievement, with the attention it has garnered, has important scientific signifi cance and potential social and economic value," said Chen Zhu, the minister of health PRC and also the former associate dean of the China Academy of Sciences (http://www.simm.ac.cn/News/20071417649.htm , available as of January 4, 2007). Other encouraging news came from the Shanghai Life Sciences Institute. A novel anti-HIV compound named Nifeviroc was developed with the support of the municipal government and licensed for clinical trials on April 17, 2007 (Shanghai Daily, April 17, 2007). This is expected to become the world's first oral HIV entryinhibitor. Thus far, applications to patent Nifeviroc have been submitted in 14 countries and regions, including the United States, Japan, and the European Union. Recently, Shanghai Targetdrug Pharmaceutical Company and Avexa, a Melbourne-based drug-research company in Australian, announced that they will jointly develop Nifeviroc for global distribution. Avexa will handle post-research expenses, develop the drug in the international marketplace, and share global profits with Targetdrug. Thus, China may have justified rationale and confidence to believe that the day will come when China's pharmaceutical products will boast a strong presence in the global market.

China's efforts to shed its title of "Leader in liver disease".

According to Xinhua News, Chen Zhu, China's Minister of Health, mentioned at the 2007 Annual Conference of the China Association for Science and Technology (CAST) that an action plan for the diagnosis and treatment of hepatitis B could control hepatitis B virus (HBV) infection to below 1% by 2050. This plan is one of the Health Ministry's goals for middle-long-term development planning in medical science and technology that China is endeavoring to reach (http://hbv.39.net/079/18/127612.html, available as of September 18, 2007). The Ministry's strategy involves a series of action plans for other areas like HIV, tuberculosis, malignant tumor control, and mental health, but chronic HBV therapy is more important and more urgent. HBV infection is a leading cause of illness and death in China. Approximately 60% of the population has a history of HBV infection, and 9.8% of persons in China are chronically infected with HBV and at risk for premature death from liver disease. Each year, an estimated 263,000 persons in China die from HBV-related liver cancer or cirrhosis, accounting for 37%~50% of HBV-related deaths worldwide (Available as a report from the Centers for Disease Control and Prevention (CDC), 2007;56:441-445. http://www.cdc.gov/mmwr/previe / mmwrhtml/mm5618a2.htm, May 11, 2007). Besides China, HBV is highly prevalent in approximately 45% of the global population and is found in the Far East, parts of the Middle East, sub-Saharan Africa, parts of South America, and the Amazon basin, where at least 8% of the population are HBV chronic carriers (hepatitis B surface antigen [HBsAg] positivity rates > 8%) (Figure 1) (Int J Med Sci 2005;2:50-57). China seems to have become a "Leader in liver disease." Annually, more than 1,000 billion RMB is spent on HBV therapy and prevention, while the resulting indirect economic losses are inestimable. The reasons for the high rates of chronic HBV infection in China are complex. First, HBV infection has broad clinical manifestations, including asymptomatic carriers, acute hepatitis, and chronic (lifelong) hepatitis, due to different immune reactions by the host. However, little is currently known about the mechanisms for HBV's unremitting infection and long-term nonprogressive HBV infection of asymptomatic HBV carriers. Although a safe and effective vaccine against HBV has been available since 1982, there are still approximately 5~10% nonresponders to the hepatitis B vaccine. Moreover, little is known about the possible immunogenetic mechanisms of HBV-infected individuals developing cirrhosis and hepatocellular carcinoma, which are considered to be the biggest bottleneck for HBV therapy. Second, some social factors may explain the high rates of HBV infection. The public often pales at the mention of HBV infection, but they have incorrect perceptions or little knowledge about how hepatitis B is transmitted, resulting in inadequate self-prevention, unfounded prejudices, or unfair treatment of the chronically infected. Worse, even many physicians are not aware of the risk, the association between hepatitis B and liver cancer, the importance of HBV vaccination to prevent infection, and the need for carriers to have regular liver cancer screening. The latter is important because a carrier is an infected individual who does not develop the disease but can transmit the virus to others. Research has proven that the hepatitis B virus is mainly transmitted through body fluids like blood, semen, vaginal or menstrual secretions, serum, and wound exudates, and the virus has also been found in saliva, amniotic fl uid, tears, urine, feces, sweat, and mother's milk (Int J Med Sci 2005;2:50-57). Thus, people should actively acquire HBV-related knowledge, perform good hygiene, and heighten individual awareness of prevention to contain the transmission of HBV, which is of great importance to everyone. Finally, poor living habits are another important factor. In most rural areas in China, and especially in the poverty-stricken areas inhabited by smaller ethnic groups, people still lead poor lifestyles and have poor health habits, leading to their decreased immunity to HBV. This, to a certain extent, may be attributed to the inadequate public health advertising and financial input of the Government. Except in some large general hospitals, the sanitary conditions of most hospitals and rural health clinics still need to be improved, including a system of social relief and assistance. Another important aspect is attributed to people's lack of awareness concerning regular physical examinations. Many chronically infected individuals may not know that they have been infected because they feel perfectly healthy. By the time symptoms develop, however, action will be too late. The public is glad to see that a series of measures have been taken by Chinese authorities to provide effective HBV treatment and prevention. For instance, the "Wang Bao-En hepatic fibrosis research fund" was established by the China Foundation for Hepatitis Prevention and Control (CFHPC) on January 30, 2007 for the financial support of HBV research (Xinhua News, http://news.xinhuanet.com/health/2007-02/02/content 5687887.htm, available as of February 2, 2007). Similarly, the " Vaccination against Hepatitis B & Health Education Program," supported by the CFHPC, the Asian Liver Center at Stanford University, and several philanthropic foundations in Hong Kong, was formally inaugurated on August 31, 2007 to provide students of Qinghai Province with free and fullrange protection with hepatitis B vaccination (CFHPC News, http://www.cfhpc.net/CN/News/Detail.asp?gCatalogID=3&SystemID=79, available as of August 31,2007). The PRC is currently forming exceptional scientific teams, both from clinical and research institutes, to study the integrity, development, and natural history of HBV as well as mechanisms for unremitting HBV infection in terms of aspects such as the virus, host, and environment. In the meantime, researchers are endeavoring to develop novel anti-hepatitis virus drugs pursuant to the "Guideline for Prevention and Treatment of Chronic Hepatitis B" enacted at the end of 2004. As Health Minister Chen Zhu said, "China must cast its title of 'Leader in liver disease' into the Pacific Ocean because," he added, "we already have an extremely effective vaccine against HBV."

Electron microscopy study on a new phase in beta-titanium alloys aged at a high temperature.

In a Ti-20mass%Mo alloys aged by two steps aging at 623 and 823K, a new phase has been observed. In the first step aging, [Formula: see text] -phase crystals appear and at the second step aging, these crystals disappear and are replaced with the newly discovered phase crystals. Observations in the dark field image and analysis of composition of the new phase crystals have shown that the formation is closely related to the [Formula: see text] -phase structure. The new phase crystals have been also observed in four kinds of [Formula: see text] -type Ti alloys and a ( [Formula: see text] ) type Ti alloy aged at high elevated temperatures. Based on high-resolution electron microscope observations, the atomic structure of the new phase is assumed.

Roles of IL-4 and other factors in the trichosanthin-induced ovalbumin-specific IgE response.

AIM: To study the mechanism of trichosanthin (TCS)-induced ovalbumin (OVA)-specific immunoglobulin E (IgE) response in vivo. METHODS: To determine whether interleukin-4 (IL-4) was involved in TCS-induced IgE production, TCS and OVA co-immunized mice were treated with anti-IL-4 monoclonal antibodies (mAb) and OVA-specific serum IgE production was measured by enzyme-linked immunosorbent assay (ELISA). To distinguish whether recombinant IL-4 (rIL-4) was sufficient to support OVA-specific IgE response, OVA alone immunized mice were treated with rIL-4 and OVA-induced IgE production were examined by ELISA in the serum. To determine whether additional factors were involved in TCS-induced IgE response, th e kinetic expression of CD40 ligand (CD40L), tumor necrosis factor-alpha (TNF-alpha), and interleukin-13 (IL-13) were measured by semi-quantitative RT-PCR in draining mesenteric lymph node (MLN) from TCS-immunized mice. RESULTS: TCS-induced OVA-specific IgE production was suppressed by anti-IL-4 antibody, whereas IL-4 alone could not induce OVA-specific IgE production. CD40L, TNF-alpha, and IL-13 all expressed high levels in MLN after both primary and secondary immune responses. Among them CD40L had the similar transient expression peak to that of IL-4. CONCLUSION: IL-4 was indispensable for TCS-induced OVA-specific IgE production, and the other three factors examined may also be involved in, but CD40L may play a more important role.

Interleukin 20: discovery, receptor identification, and role in epidermal function.

A structural, profile-based algorithm was used to identify interleukin 20 (IL-20), a novel IL-10 homolog. Chromosomal localization of IL-20 led to the discovery of an IL-10 family cytokine cluster. Overexpression of IL-20 in transgenic (TG) mice causes neonatal lethality with skin abnormalities including aberrant epidermal differentiation. Recombinant IL-20 protein stimulates a signal transduction pathway through STAT3 in a keratinocyte cell line, demonstrating a direct action of this ligand. An IL-20 receptor was identified as a heterodimer of two orphan class II cytokine receptor subunits. Both receptor subunits are expressed in skin and are dramatically upregulated in psoriatic skin. Taken together, these results demonstrate a role in epidermal function and psoriasis for IL-20, a novel cytokine identified solely by bioinformatics analysis.