Progress in the Use of Glucocorticoids and Biological Agents in Non-Infectious Uveitis

One of the main immune-mediated diseases that lead to avoidable blindness is non-infectious uveitis. Glucocorticoids are the first-line therapy choice for noninfectious uveitis;however, biologics are also showing promise in the management of this condition. The description of glucocorticoid and biologic usage in non-infectious uveitis is the main topic of this paper.

Effect of biological agents on survival rate and root growth of Scots Pine seedlings

Two-year-old Scots pine (Pinus sylvstris var.mongolica) seedlings were treated with Pt mycorrhiza powder, ABT root-growing powder, HRC water-absorbing agent and high-yield powder, and planted on the sandy land in Balinyouqi, Inner Mongolia (180°12′13″E and 43°13′05″N). The effect and function of these biological agents on survival rate of seedlings were tested and analyzed by measuring the fine root growth and gross root growth. The results showed that the survival rates of the seedlings treated with Pt3, ABT, and HRC biological agents increased by 29.3%, 23.6%, and 16%, respectively. The regression analysis revealed that the length of fine roots (<2 mm) was positively correlated with seedling survival rate, which means that the Pt3 powder, ABT foot-growing powder and HRC water-absorbing powder increased the survival rates of the seedlings by promoting the growth of fine roots. Keywords Biological agents - Pinus sylvstris var.mongolica - Sandy soil - Roots - Survival rate CLC number S723.1 - S791.253 Document code A Foundation item: This article was supported by the National Natural Science Foundation of China (No. 39970627).Biography: TANG Feng-de (1967-), male, Ph. Doctor in Institute of Applied Ecology. Chinese Academy of Sciences, Shenyang 110016, P. R. China.Responsible editor: Zhu Hong

Secondary Metabolites of Entomopathogenic Fungi, Biological Alternative for the Control of Agricultural Pests and Disease: Present and Perspectives

The use of entomopathogenic fungi (EF) in recent years has been highly effective against the different orders of insects considered pests of agricultural importance and their conidia have been commonly applied, but it has been reported that these are sensitive to the environmental conditions. For this reason, biopesticides products have been formulated based on secondary metabolites, recently. These biomolecules participate as biological control agent, such as: cyclic depsipeptides, amino acids, polyketides, polyphenols and terpenoids, affecting their morphology, life cycle and insect behavior. The use of secondary metabolites of entomopathogenic fungi opens the possibility of application in a more efficient way for the control of agricultural pests in a compatible with the environment and human health;therefore, it is important to know, analyzing the type of molecules, their effects, and their different methods of application.

Infliximab is superior to other biological agents for treatment of active ulcerative colitis:A meta-analysis

AIM: To compare the efficacy and safety of biological agents for the treatment of active ulcerative colitis(UC).METHODS: PubMed, MEDLINE, EMBASE and the Cochrane library were searched to screen relevant articles from January 1996 to August 2014. The mixedtreatment comparison meta-analysis within a Bayesian framework was performed using WinBUGS14 software.The proportions of patients reaching clinical response,clinical remission and mucosal healing in induction and maintenance phases were analyzed as efficacy indicators. Serious adverse events in maintenance phase were analyzed as safety indicators.RESULTS: The meta-analysis results showed that biological agents achieved better clinical response,clinical remission and mucosal healing than placebo.Indirect comparison indicated that in induction phase,infliximab was more effective than adalimumab in inducing clinical response(OR = 0.41, 95%CI:0.29-0.57), clinical remission(OR = 0.33, 95%CI:0.19-0.56) and mucosal healing(OR = 0.33, 95%CI:0.19-0.56), and golimumab in inducing clinical response(OR = 0.66, 95%CI: 0.39-2.33) and mucosal healing(OR = 2.15, 95%CI: 1.18-4.22). No significant difference was found between placebo and biological agents regarding their safety.CONCLUSION: All biological agents were superior to placebo for UC treatment in both induction and maintenance phases with a similar safety profile, and infliximab had a better clinical effect than the other biological agents.

Control of Lymantria dispar L. by biological agents

The experiment on control of Lymantria dispar L by using different kinds ofbiological measures, including nuclear polyhedrosis virus (NPV) of Lymantria dispar L., BtMP-342,sex-attractant as well as botanical insecticide, was carried out in the forest regions of InnerMongolia in 2003. Two concentrations (2.632x10^6 PIB ? ml^(-1) and 2.632x10^7 PIB ?ml^(-1)) of Lymantria dispar L. NPV were sprayed on the 2rd-instar-larvae of L. dispar and 70% and77.8% control effect were obtained respectively. BtMP0-342 was applied to the 3rd- and 4th-instarlarvae and the control effect was around 80%. The sex-attractant provided by Canada Pacific ForestryResearch Center also showed a good result in trapping L. dispar adults. The self-produced botanicalinsecticide, which was extracted from a kind of poisonous plant distributed in Daxing'an Mountains,China, exhibited a good control result in controlling the larvae of L. dispar, and 82% mortalitywas observed when spraying primary liquid of the botanical insecticide on the 3rd-5th-instar-larvaein lab.

Parasitoid wasps as effective biological control agents

Biological control(biocontrol) is a safe, sustainable approach that takes advantage of natural enemies such as predators, parasitic insects or pathogens to manage pests in agroecosystems. Parasitoid wasps, a very large evolutionary group of hymenopteran insects, are well-known biological control agents for arthropod pests in agricultural and forest ecosystems. Here, we summarize the recent progress on the application of parasitoid wasps in biocontrol in China for the last five years. These include species diversity of parasitoid wasps, identification of dominant parasitoid wasps associated with insect pests and biocontrol practices(three types of biological control, i.e., classical, augmentative and conservation biological control) in several Chinese agroecosystems. We then treat different mass-rearing and release technologies and the commercialization of several parasitoid wasp species. We also summarize other work that may have a potential use in biocontrol, including the effect of plant volatiles on parasitoids and recent advance in the molecular mechanisms underlying the host regulation by parasitoid wasps. Future research area and applied perspectives are also discussed, noting that advances in biocontrol technologies in Chinese agriculture informs research at the global level.

Fire Blight Disease Caused by Erwinia amylovora on Rosaceae Plants in Kyrgyzstan and Biological Agents to Control This Disease

Erwinia amylovora species were isolated from the blossoms, exudates, infected fruits, leaves and bent branches of diseased apple, pear and hawthorn trees, selected in the Chy, Osh and Jalal Abad regions. Biochemical and pathogenicity tests, alongside PCR analyses, were conducted to identify the local isolates of Erwinia amylovora. The alternative antagonistic microorganisms which combat bacterium E. amylovora were tested within in vitro and in vivo conditions. The results revealed the ability of Streptomyces antagonistic bacteria to decrease fire blight severity on pear and apple trees during the first stage of the fire blight disease in leaf tissues. Streptomyces strain C1-4 suppressed E. amylovora disease symptoms in the leaf tissues and excised apple and pear shoots. The incidence of fire blight on leaves was reduced by about 70% with two applications of bacterial antagonists. Further studies at different locations in Kyrgyzstan, using large scale application, would allow for stronger recommendations to be made, including studies and recommendations on their ability to prevent disease and to use them as main components in an integrated pest management program.

Colitis associated with biological agents

In the past,there has been considerable focus on a host of drugs and chemicals that may produce colonic toxicity.Now,a variety of new biological monoclonal antibody agents,usually administered by infusion,have appeared in the clinical realm over the last decade or so to treat different chronic inflammatory or malignant disorders.For some of these agents,adverse effects have been documented,including apparently new forms of immune-mediated inflammatory bowel disease.In some,only limited symptoms have been recorded,but in others,severe colitis with serious complications,such as bowel perforation has been recorded.In others,adverse effects may have a direct vascular or ischemic basis,while other intestinal effects may be related to a superimposed infection.Some new onset cases of ulcerative colitis or Crohn's disease may also be attributed to the same agents used to treat these diseases,or be responsible for disease exacerbation.Dramatic and well documented side effects have been observed with ipilimumab,a humanized monoclonal antibody developed to reduce and overcome cytotoxic T-lymphocyte antigen 4,a key negative feedback regulator of the T-cell anti-tumor response.This agent has frequently been used in the treatment of different malignancies,notably,malignant melanoma.Side effects with this agent occur in up to 40% and these are believed to be largely immune-mediated.One of these is a form of enterocolitis that may be severe,and occa-sionally,fatal.Other agents include rituximab(an antiCD20 monoclonal antibody),bevacizumab(a monoclonal antibody against the vascular endothelial growth factor) and anti-tumor necrosis factor agents,including infliximab,adalimumab and etanercept.

Dosage Screening and Effect Evaluation of Biological Agents against Cotton Verticillium Wilt through Drip Irrigation

Drip irrigation of biological agents is an important green pathway to prevent diseases in Xinjiang cotton fields, especially soil-borne diseases. In order to clear the suitable dosage of different biological agents for controlling cotton Verticillium wilt, field split plot experiment was designed to research the control effects of Bacillus subtilis WP (15, 30 and 45 kg/hm^2), Shibeijian Trichoderma harzianum (15, 18 and 24 kg/hm^2), Yufeng“99”(15, 22.5 and 30 kg/hm^2), Zhongnonglukang (30, 45 and 60 kg/hm^2) and Athomin (45, 60 and 75 kg/hm^2) on cotton Vertillium wilt in 2016 and 2017. The disease control effect against cotton Verticillium wilt, cotton growth, cotton yield and fiber quality were compared and analyzed by biometrical method. The results showed that five biological agents significantly reduced the incidence rate and disease index of cotton Verticillium wilt, and the average control effect reached 33.50%-74.94%. The control effect of Shibeijian T. harzianum dripped at the dosage of 18 kg/hm^2 was significantly higher than that dripped at 15 and 24 kg/hm^2. There was no significant difference between different application dosages in Athomin treatment. The control effect of the remaining three agents had significantly positive correlation with application dosage. Five biological agents had obvious promotion effects on cotton growth, and the cotton height, width of the top fourth leaf, fruit branch number and boll number per plant were increased in different levels. The cotton height and width of the top fourth leaf had no obvious changes with the increase of dosage, while the fruit branch number and boll number increased with the increasing dosage. Meanwhile, these biological agents significantly advanced the maturity of cotton. Except for Athomin treatment, the cotton seed yield in other treatments showed an increasing trend and increased significantly with the increasing dosage. The cotton fiber length and fiber breaking tenacity were improved slightly, but cotton quality had not been improved conspicuously. Therefore, according to disease control effect, cotton growth and yield performance, the suitable drip dosage of biological agents were as follows: Yufeng "99" 30 kg/hm^2, Zhongnonglukang 60 kg/hm^2, B. subtilis WP 45.0 kg/hm^2, and Shibejian T. harzianum 18.0 kg/hm^2. The drip dosage of Athomin still needs to be further studied.

Control Effects of a New Sex Pheromone Trap and Biological Agents on Sesamia inferens Walker and Argyroploce schistaceana (Snellen)

This study was conducted to explore and seek high-efficiency and safe green control techniques on sugarcane borers,promote green control of diseases and pests of sugarcane and build a resource-conserving,environmentally friendly and sustainable governance system of diseases and pests of sugarcane.A new sex pheromone trap of sugarcane borers,abamectin· Bacillus thuringiensis (Bt) and tebufenozide were selected and applied in field trials.The use of the new sex pheromone trap of sugarcane borers (6 traps/hm 2) in combination with 0.05% abamectin·10 billion active gemmae/g B.thuringiensis (Bt) WP (1.8 kg/hm 2) or new sex pheromone trap of sugarcane borers (6 traps/hm 2) in combination with 200 g/L tebufenozide SC (1.5 L/hm 2) were the best in the sugarcane production.New sex pheromone trap of sugarcane borers should be installed in early march,and biological agents were mixed with water 900 kg per hectare and sprayed evenly sugarcane plants at the beginning of April.Their control effects of dead heart rate and bored stalk rate could be more than 69.98% and 49.09%,respectively,which were superior to that of the control pesticide 3.6% bisultap GR (90 kg/hm 2).The results showed that new sex pheromone trap of sugarcane borers in combination with abamectin· B.thuringiensis (Bt) or tebufenozide was the optimum mode of green control techniques on sugarcane borers.When it was alternately or coordinately used with other technology,it could delay the emergence and development of drug resistance,and it was worthy of widespread popularization and application in sugarcane area.

The Use and Exchange of Biological Control Agents for Food and Agriculture

The report sets out to summarize the past and current situation regarding the practice of biologicalcontrol inrelationtothe use and exchange of genetic resources relevant for BCAs.It considers the twomain categories of biological control:classical and augmentative.Allowing access to BCAs for use inanother country imposes no risk of liability to the source country.Local scientific knowledge abouthabitats,fauna andflora,can be

Topical biological agents targeting cytokines for the treatment of dry eye disease

Because inflammation plays a key role in the pathogenesis of dry eye disease and Sjogren's syndrome, topical anti-inflammatory agents such as corticosteroids and cyclosporine A have been used to treat inflammation of the ocular surface and lacrimal gland. Systemic biological agents that target specific immune molecules or cells such as tumor necrosis factor(TNF)-α, interferone-α, interleukin(IL)-1, IL-6, or B cells have been used in an attempt to treat Sjogren's syndrome. However, the efficacy of systemic biological agents, other than B-cell targeting agents, has not yet been confirmed in Sjogren's syndrome. Several studies have recently evaluated the efficacy of topical administration of biological agents targeting cytokines in the treatment of dry eye disease. Topical blockade of IL-1 by using IL-1 receptor antagonist could ameliorate clinical signs and inflammation of experimental dry eye. Using a mouse model of desiccating stress-induced dry eye, we have demonstrated that topical application of a TNF-α blocking agent, infliximab, could improve tear production and ocular surface irregularity, decrease inflammatory cytokines and Th-1 CD4+ cells on the ocular surface, and increase gobletcell density in the conjunctiva. Although controversy still remains, the use of topical biological agents targeting inflammatory cytokines may be a promising therapy for human dry eye disease.

Advances in the treatment of IgA nephropathy with biological agents

Immunoglobulin A nephropathy(IgAN)is the most common primary glomerular disease,and the“four-hit”theory represents its currently accepted pathogenic mechanism.Mucosal immunity triggered by infections in the respiratory tract,intestines,or other areas leads to antigen presentation,T cell stimulation,B cell maturation,and the production of IgA-producing plasma cells.The proteins B-lymphocyte stimulator(BLyS)and a proliferation-inducing ligand(APRIL)are involved in this process,and alternative complement and lectin pathway activation are also part of the pathogenic mechanism.Kidney Disease Improving Global Outcomes guidelines indicate that a specific effective treatment for IgAN is lacking,with renin-angiotensin-aldosterone system inhibitors being the primary therapy.Recent research shows that biological agents can significantly reduce proteinuria,stabilize the estimated glomerular filtration rate,and reverse some pathological changes,such as endocapillary proliferation and crescent formation.There are four main categories of biological agents used to treat IgA nephropathy,specifically anti-CD20 monoclonal antibodies,anti-BLyS or APRIL monoclonal antibodies,monoclonal antibodies targeting both BLyS and APRIL(telitacicept and atacicept),and monoclonal antibodies inhibiting complement system activation(narsoplimab and eculizumab).However,further research on the dosages,treatment duration,long-term efficacy,and safety of these biological agents is required.

Expert Consensus on the Treat-to-Target Strategy for Psoriasis With Biological Agents in China(Simplified Edition)

Psoriasis is a chronic,recurrent,inflammatory systemic disease that is not only characterized by skin manifestations but may also be accompanied by various comorbidities,imposing a heavy burden on patients’physical and mental health and affecting their quality of life.Although the continuous approval of various biological agents for clinical use has provided more effective treatment options to patients with psoriasis,no consensus on the evaluation of comprehensive treatment goals has yet been established.The treat-to-target(T2T)strategy requires consideration of multiple dimensions of treatment outcomes,the development of long-term management goals,and regular assessments of treatment conditions,which are often used in the management of chronic diseases.Therefore,based on the latest consensuses and guidelines,research data,and clinical experience as well as the combination of survey results and expert group discussions,the present consensus focuses on 4 dimensions of short-and long-term integrated management goals for biological agents:alleviating skin lesions,improving quality of life,screening and managing psoriasis comorbidities,and ensuring drug safety.The implementation methods,evaluation time,treatment monitoring,and program adjustments are also herein described to achieve comprehensive management of psoriasis to the maximum extent.This consensus provides a reference for clinical practice.

Bacterial Infection in the Limbs of Patients with Rheumatoid Arthritis during Biological Agent Therapy

Biological therapies in rheumatoid arthritis (RA) are known to increase the risk of serious infections. The present study was performed to evaluate the clinical features of bacterial infections occurring in the limbs during biological therapies in patients with RA. By March 2011, 11 RA patients (14 limbs) treated with biological agents at our institution required hospitalization due to bacterial infections occurring in the limbs. These patients had an average age of 53.7 years old. Infections occurred an average of 19 months after biological treatment. Two limbs in one patient were treated with infliximab, eight limbs in six patients were treated with etanercept, one limb in one patient was treated with adalimumab, and three limbs in three patients were treated with tocilizumab. Cellulitis occurred in 7 limbs, late infections after total knee arthroplasty occurred in two limbs, early infections after orthopedic surgery occurred in three limbs, and septic arthritis occurred in two limbs. Four cases had comorbidities—liver cirrhosis and diabetes mellitus in one and three cases, respectively. All patients were treated using corticosteroid with an average dose of 4.6 mg daily. Seven limbs required surgical treatment. All patients finally recovered. Ten limbs continued treatment with biological agents. Care must be taken regarding bacterial infection in the limbs of RA patients treated by using biological agents, particularly those with comorbidities. Further studies are required to confirm means of preventing such infections in daily practice.

Biologic Agents in Behcet’s Disease:Our Experience and Review of the Literature

Behcet’s disease (BD) is a large vessel vasculitis with a wide range of clinical manifestations. Some of these manifestation may be life threatening and rapid suppression of the inflammation with effective immunosuppressive agent is crucial. There are traditional drugs with different response rates and all have efficacy on different manifestations of the disease. The most frightening manifestations of the disease are ocular, neurologic, intestinal and vascular types of involvement. Besides benign and easily treated manifestations there are also refractory cases with complicated involvement. The novel biologic agents have been used for these resistant patients and favorable response rates have been reported. In this review, we have shared our experience with biologic agents in BD and also reviewed the literature for the efficacy and safety for these novel agents for refractory patients.

Interleukin 12/interleukin 23 pathway: Biological basis and therapeutic effect in patients with Crohn's disease

Considering that both innate and adaptive immune responses are involved in the pathogenesis of Crohn's disease(CD), novel therapeutic options have significantly been developed. Biological agents represent an important addition to the conventional treatments for immuno-inflammatory conditions, acting as antagonists of adhesion molecules or various inflammatory cytokines. The interleukin 12(IL-12)/IL-23 common pathway has been found to play a determinant role in the induction of inflammation in adaptive immune responses. In particular, IL-23 promotes the differentiation of na?ve T helper cells into Th17 phenotype with the concomitant secretion of several inflammatory cytokines such as IL-17 and IL-22, whereas IL-12 induces the Th1 polarization and production of critical cytokines such as interferon-γ and tumor necrosis factor. Nowadays, there is increased interest regarding the role of IL-23 as a therapeutic target of CD through the blockage of IL-23 mediated pathways. In this editorial, we focus on the role of IL-12/IL-23 pathway in the regulation of mucosal immunity and in the induction and maintenance of chronic inflammation. In parallel, we critically discuss the available data regarding the therapeutic effect of the IL-12/IL-23 inhibitors and especially of ustekinumab, a human monoclonal antibody which has been recently approved by the United States Food and Drug Administration for the management of moderateto-severe CD and its potential to be used as first-line therapy in everyday clinical practice.

Outcomes assessment of hepatitis C virus-positive psoriatic patients treated using pegylated interferon in combination with ribavirin compared to new Direct-Acting Antiviral agents

AIM To evaluate the outcomes in biological treatment and quality of life of psoriatic patients with chronic hepatitis C(CHC) treated with new Direct-Acting Antiviral agents(DAAs) compared to pegylated interferon-2α plus ribavirin(P/R) therapy.METHODS This is a retrospective study involving psoriatic patients in biological therapy who underwent anti-hepatitis C virus(HCV) treatment at the Department of Dermatology Galeazzi Orthopaedic Institute Milan, Italy from January 2010 to November 2017. The patients were divided into two groups: patients that underwent therapy with DAAs and patients that underwent HCV treatment with P/R. Patients were assessed by a dermatologist for psoriasis symptoms, collecting Psoriasis Area Severity Index(PASI) scores and the Dermatology Quality of Life Index(DLQI). PASI and DLQI scores were evaluated 24 wk after the end of HCV treatment and were assumed as an outcome of the progression of psoriasis. Switching to a different b DMARD was considered as an inadequate response to biological therapy. The dropout of HCV therapy and sustained virological response(SVR) were considered as outcomes of HCV therapy.RESULTS Fifty-nine psoriatic patients in biological therapy underwent antiviral therapy for CHC. Of this, 27 patients were treated with DAAs and 32 with P/R. After 24 wk post treatment, the DLQI and the PASI scores were significantly lower(P < 0.001 and P < 0.005, respectively) in the DAAs group compared with P/R group. None of the patients in the DAAs group(0/27) compared to 8 patients of the P/R group(8/32) needed a shift in biological treatment.CONCLUSION DAAs seem to be more effective and safe than P/R in HCV-positive psoriatic patients on biological treatment. Fewer dermatological adverse events may be due to interferon-free therapy.

Surgery for Crohn's disease in the era of biologicals:A reduced need or delayed verdict?

Crohn's disease(CD) is a chronic inflammatory bowel disease that can affect the entire gastrointestinal tract.Ultimately,up to 70% of all patients will need surgery,despite optimized medical therapy.Moreover,about half of the patients will need redo-surgery because of disease recurrence.The introduction of anti-tumor necrosis factor(TNF) drugs(Infliximab in 1998) revolutionized the treatment of CD.Different randomized trials assessed the efficacy of anti-TNF treatment not only to induce,but also to maintain,steroid-free remission.Furthermore,these agents can rapidly lead to mucosal healing.This aspect is important,as it is a major predictor for long-term disease control.Subgroup analyses of responding patients seemed to suggest a reduction in the need for surgery at median-term follow up(1-3 years).However if one looks at population surveys,one does not observe any decline in the need for surgery since the introduction of Infliximab in 1998.The short follow-up term and the exclusion of patients with imminent surgical need in the randomized trials could bias the results.Only 60% of patients respond to induction of anti-TNF therapy,moreover,some patients will actually develop resistance to biologicals.Many patients are diagnosed when stenosing disease has already occurred,obviating the need for biological therapy.In a further attempt to change the actual course of the disease,top down strategies have been progressively implemented.Whether this will indeed obviate surgery for a substantial group of patients remains unclear.For the time being,surgery will still play a pivotal role in the treatment of CD.

Modification of methyl oleate for silicon-based biological lubricating base oil

A new kind of silicon-based biological lubricating base oil with good viscosity-temperature behavior,viscosity index,thermostability,oxidation stability and wear resistance performance was synthesized as a derivative of methyl oleate.Trimethylsilylation reaction was introduced to further improve methyl oleate oxidation stability and lubricity after epoxidation and open-ring reactions.The order of effectiveness of acid binding agent was N,N-diisopropylethylamine(DIEA) > pyridine > diethylamine > triethylamine,and the effects of various parameters on the trimethylsilylation reaction as well as on the silicon-oxygen bond stability and reaction yield were studied.A maximum yield of 34.54%was achieved at hydroxyl/trimethyl chlorosilane/DIEA molar ratio of1:1.25:1,reaction temperature 40℃,reaction time 1.5 h.