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.

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.

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.

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.

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.

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

Technique of Earthworms Restoring Soil in Greenhouse Cultivation

The production environment of greenhouse cultivation is relatively closed,the multiple cropping index is high,the management of fertilizationwatering and pesticideapplication isblindtosomeextent,andthe phenomenonofcontinuous cropping isalsocommonSoilquali-ty affects the sustainable development of greenhouse cultivation.Earthworm is a ubiquitous invertebrate organism in soil,an important part of soil system,a link between terrestrial organisms and soil organisms,an important link in the small cycle of soil material organisms,and plays an important role in maintaining the structure and function of soil ecosystem.Different ecotypes of earthworms are closely related to their habi-tats(soil layers)and food resource preferences,and then affect their ecological functions.The principle of earthworm regulating soil function is essentially the close connection and interaction between earthworm and soil microorganism.Using different ecotypes of earthworms and bio-logical agents to carry out combined remediation of greenhouse cultivation soil is a technical model to realize sustainable development of green-house cultivation.

Accidents at Work from Exposure to Biological Material Contamination of Viral Hepatitis“B”and“C”in a Brazilian Capital

Background: Occupational exposure to biological materials is a serious risk to the health of workers in their workplaces, due to the possibility of transmitting pathogens such as Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), and Human Immunodeficiency Virus (HIV). The aim of this study was to analyze the accidents of exposure to biological material which resulted in contamination of Hepatitis B and C in the municipal health Belo Horizonte. Methods: Epidemiological study with cross-sectional design performed by querying the data on accidents at work involving exposure to biological materials and notification data of Viral Hepatitis in the Information System for Notifiable Diseases (SINAN) for the period of 2007 to June 2011, filed with the municipal government of Belo Horizonte. A descriptive analysis was performed using frequency distribution and percentages. Results: The 45 research records were arranged in professional categories, with 57.77% of incidents being ignored, followed by 24.44% nursing technicians, 6.66% nursing assistants, and 2.22% marketers, housekeeping, administrators, janitors, and builders. The average age was 39 years and 64.44% of the professionals were female. At the notification of the accident, 75.55% of professionals were not registered at CAT, and 92.85% of exposures occurred in the hospital;64.29% in contact with blood;35.71% of the causative agent was without needle lumen, 28.57% during administration of intravenous medication, and 57.14% from percutaneous exposure. In the distribution of occupation, 57.78% were contaminated with viral Hepatitis B and C. With vaccination regimens for Hepatitis B, 66.67% of the cases went to nursing assistants and 42.22% were “ignored”. Conclusion: These data confirm the need for reorientation of working practices during daily activities of health workers and guidance for notification of occupational accidents involving biological material and viral Hepatitis B and C in order to improve the quality of the records.

Physical-biological Collaborative Prevention and Control of Facility Strawberry Continuous Cropping Diseases

The aim was to develop green strawberry varieties,control soil-borne diseases from facility strawberry continuous cropping,improve the safety and quality of strawberries and promote the healthy and stable development of the strawberry industry. Based on the production practices in recent years,we summarized the physical-biological collaborative prevention and control technology for the disease of facility strawberry continuous cropping facilities,established the technical goals,the main types of soil-borne diseases,and the physical-biological collaborative control prevention and control technologies,mainly including the specific methods and technical points of solar high temperature disinfection technology and biological bacterial fertilizer（ agent） treatment technology.

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.

Crohn's disease and clinical management today:How it does?

Crohn’s Disease(CD)is an Inflammatory Bowel Disease and is characterized by an immune-mediated nature.Its etiology results from the interaction between genetic,enviromental and microbial factors.Regarding pathophysiology,it involves high levels of interleukin(IL)-12,IL-17,and Th1 profile,along with loss of tolerance mechanisms,an increase in pro-inflammatory interleukins,beyond the possibility to affect any part of the gastrointestinal tract.Its symptoms include abdominal pain,chronic diarrhea,weight loss,anorexia,and fatigue,as well as blood in the stool or rectum.Additionally,conditions comprising musculoskeletal,cutaneous,ocular,hepatic,and hematological alterations may be associated with this scenario and extra-intestinal presentation,such as erythema nodosum,anterior uveitis,osteoporosis,and arthritis can also occur.Today,clinical history,exams as fecal calprotectin,ileocolonocopy,and capsule endoscopy can be performed in the diagnosis investigation,along with treatments to induce and maintain remission.In this sense,anti-inflammatory drugs,such as corticosteroids,immunomodulators,and biological agents,as well as surgery and non-pharmacological interventions plays a role in its therapy.The aim of this review is to bring more current evidence to clinical management of CD,as well as to briefly discuss aspects of its pathophysiology,surveillance,and associated disorders.

Rice(Oryza sativa L.)plant protection using dual biological control and plant growth-promoting agents:Current scenarios and future prospects

Various microorganisms live in association with different parts of plants and can be harmful,neutral,or beneficial to plant health.Some microbial inhabitants of plants can control plant diseases by contesting with,predating on,or antagonizing plant pathogens and by inducing systems for plant defense.A range of methods,including plant growth-promoting microorganisms(PGPMs)as biological control agents(BCAs)(BCA-PGPMs)are used for the biological management and control of plant pathogens.Some BCAs interact with plants by inducing resistance or priming plants without direct interaction with the pathogen.Other BCAs operate via nutrient competition or other mechanisms to modulate the growth conditions for the pathogen.Generally,PGPMs can be applied alone or together with other chemicals or carriers to control various crop diseases.This review highlights the effective types of BCA-PGPMs and their applications,roles,carrier based-formulations,and responses to rice(Oryza sativa L.)pathogens.Future plant disease management prospects are promising,and growers’increasing demand for BCA-PGPM products can be exploited as an effective approach to the management of plant diseases,as well as to improve yield,environmental protection,biological resources,and agricultural system sustainability.

Chronic Refractory Idiopathic Urticaria

Background: Chronic spontaneous urticaria (CSU) is a complex medical condition characterized by substantial morbidity and a negative impact on one’s quality of life. There are several treatment approaches available, tailored to the severity of the condition, which can enhance overall quality of life. Aim: In this article, we outline a systematic approach to managing chronic urticaria, while also elucidating the available treatment strategies for cases that prove resistant to conventional therapies. To illustrate our points, we present a clinical case as a practical example. Case Presentation: Here, we present a patient with CSU since childhood who presented in the context of refractory hives and generalized arthralgia that responded well to omalizumab therapy with no further relapse. Conclusion: Omalizumab is a biological agent that offers a potential treatment option for CSU. It is available for individuals twelve years and older who have not responded well to conventional treatments. It has demonstrated good efficacy with a relatively low rate of clinically significant adverse effects. Nonetheless, there is a dearth of research regarding the optimal method for tapering the dosage and determining the duration of treatment.

Methylprednisolone microsphere sustained-release membrane inhibits scar formation at the site of peripheral nerve lesion

Corticosteroids are widely used for the treatment of acute central nervous system injury. However, their bioactivity is limited by their short half-life. Sustained release of glucocorticoids can prolong their efficacy and inhibit scar formation at the site of nerve injury. In the present study, we wrapped the anastomotic ends of the rat sciatic nerve with a methylprednisolone sustained-release membrane. Compared with methylprednisone alone or methylprednisone microspheres, the methylprednisolone microsphere sustained-release membrane reduced tissue adhesion and inhibited scar tissue formation at the site of anastomosis. It also increased sciatic nerve function index and the thickness of the myelin sheath. Our findings show that the methylprednisolone microsphere sustained-release membrane effectively inhibits scar formation at the site of anastomosis of the peripheral nerve, thereby promoting nerve regeneration.

A novel anti-inflammatory and immunomodulatory drug CP-25 alleviated collagen induced arthritis by down-regulating BAFF-NF-κκB signaling pathway

OBJECTIVE To investigated the regulatory effect of paeoniflorin-6′-O-benzene sulfonate(CP-25) on B cell activating factor(BAFF)/BAFF receptor-nuclear factor of kappa B(NF-κB) signaling in B cell of collagen induced-arthritis(CIA) mice.METHODS Mice CIA was induced by injection of typeⅡcollagen(CⅡ).The arthritis index(AI) and swollen joint count(SJC) were assessed,and histopathology of spleen and joints were observed.The percentage of B cells subsets,BAFF receptor expressions were analyzed by flow cytometry.BAFF and immunoglobulin(Ig) levels were measured by protein antibody array.The expressions of TRAF2,MKK3,MKK6,p-P38,and p-NF-κB65 in NF-κB signaling mediated by BAFF were analyzed by western blot.RESULTS CP-25 decreased AI and SJC,restored abnormal weights,reduced thymus index and spleen index,inhibited T/B cells proliferation,alleviated the histopathology of spleen and joints in CIA mice.CP-25 also reduced high levels of serum BAFF and immunoglobulin,decreased CD19+B cells,CD19+CD27+B cells,and CD19-CD27+CD138+plasma cells,inhibited BAFFR and TACI expressions,decreased the expressions of TRAF2,MKK3,MKK6,p-P38,and p-NF-κB65.Compared with biological agents etanercept and rituximab,CP-25 restored high T cells proliferation and percentages of B subsets to normal level,and recovered the high levels of IgA,IgD,IgG1,IgG2 a and high expressions molecules in NF-κB signaling to normal levels.The action intensity of rituximab and etanercept was more strong than CP-25.The inhibitor effects of rituximab and etanercept on AI and SJC,thymus index,proliferation of T cells and B cells subsets were strong,and down-regulated the indexes to under normal levels.CONCLUSION CP-25 might be a promising anti-inflammatory immune and regulation drug,which alleviated CIA and regulated the functions of B cells through BAFF/BAFF receptor-NF-κB signaling.

Management and outcomes of surgical patients with intestinal Behçet’s disease and Crohn’s disease in southwest China

BACKGROUND Gastrointestinal involvement in Behçet's disease(GIBD)and Crohn’s disease(CD)are inflammatory diseases sharing a considerable number of similarities.However,different from CD,the operative and postoperative management of GIBD remains largely empirical because of the lack of comprehensive treatment guidelines.AIM To compare surgical patients with GIBD and those with CD in a medical center and identify notable clinical features and effective postoperative treatment for surgical patients with GIBD.METHODS We searched patients diagnosed with CD and GIBD who underwent operations for gastrointestinal complications from 2009 to 2015 at West China Hospital of Sichuan University.A total of 10 surgical patients with GIBD and 106 surgical patients with CD were recruited.Information including demographic data,medication,and operative and postoperative parameters were collected and analyzed.As the incidence of surgical GIBD is low,their detailed medical records were reviewed and compared to previous studies.Moreover,the prognoses of CD and GIBD were evaluated respectively between groups treated with biological and non-biological agents.RESULTS Indication for first surgery was often acute intestinal perforation for GIBDpatients (7/10 vs 0/106, P < 0.001), whereas intestinal fistulae (0/10 vs 44/106, P =0.013) and ileus (0/10 vs 40/106, P = 0.015) were the indications for surgical CDpatients. Approximately 40% of patients with GIBD and 23.6% of patients withCD developed postoperative complications, 50% of patients with GIBD and 38.7%of patients with CD had recurrence postoperatively, and 40% (4/10) of patientswith GIBD and 26.4% (28/106) of patients with CD underwent reoperations. Theaverage period of postoperative recurrence was 7.87 mo in patients with Behçet'sdisease (BD) and 10.43 mo in patients with CD, whereas the mean duration fromfirst surgery to reoperation was 5.75 mo in BD patients and 18.04 mo in CDpatients. Surgical patients with GIBD more often used corticosteroids (6/10 vs7/106, P < 0.001) and thalidomide (7/10 vs 9/106, P < 0.001) postoperatively,whereas surgical patients with CD often used infliximab (27/106), azathioprine,or 6-mercaptopurine (74/106) for maintenance therapy.CONCLUSIONPatients suffering GIBD require surgery mostly under emergency situations,which may be more susceptible to recurrence and reoperation and need moreaggressive postoperative treatment than patients with CD.

Field-deployable rapid multiple biosensing system for detection of chemical and biological warfare agents

The threat of biological and chemical terror acts remains a growing worldwide concern.There is therefore a need to develop appropriate technology for the detection of chemical and biological warfare agents,with early identification intended for use by first responders.Here,we disclose the developed autonomous air sampling and detection system for evaluation of the presence of chemical and biological warfare agents that can be harmful to the population.The current device utilizes the designed mist generator-assisted air collection system(338 l min^(−1))and biosensing chip technologies,such as electrochemical measurement,Au nanoparticle-based localized surface plasmon resonance,and rapid microfluidic chip PCR for detection of minute concentrations lower than the mean lethal dose(LD_(50))of nerve gases(sarin and VX),toxic proteins(BTX/A/Hc and ricin),and pathogens(anthrax simulant).An operation time of only 5–15 min is needed for the collection and detection;sample preparation is already integrated into the system without the need for direct human intervention.In addition to the system’s sensitivity and ease of use,its portability makes it highly beneficial for first responders,which could aid in immediate risk assessment and mitigation of on-site events.

Design,synthesis and biological evaluation of novel non-azole derivatives as potential antifungal agents

A series of 3-substituted quinazolinones,2-substituted quinoxalines and 2-substituted benzopyrans were synthesized and evaluated for their antifungal activity in vitro.The new compounds revealed excellent in vitro antifungal activity with broad spectrum.The structure-activity relationships（SARs） of the derivatives were analyzed.Compound 9A2 exhibits better antifungal activity against 5 tested fungi in vitro than fluconazole,especially against Trichophyton rubrum and Microsporum gypseum.This study provides a series of novel lead compounds for the development of non-azole antifungal agents.

New options for uveitis treatment

Uveitis is one of the most important causes of blindness worldwide.Its etiology and pathogenesis are complicated and have not been well understood.The treatment for uveitis is predominantly based on steroids and immunosuppressants.However,systemic side effects limit their clinical application.With the advancement of molecular biology,some intravitreal implants and biologic agents have been used for the treatment of uveitis.Additionally,novel techniques such as gene therapy and RNA interference are being studied for using as uveitis therapy.This paper reviews recent advances in uveitis treatment.