Specific Biological Properties Research Articles

Fabrication of Hematite (α-Fe2O3) nanoparticles under different spectral lights transforms physio chemical, biological, and nanozymatic properties

Fabrication of iron oxide (Fe2O3) nanoparticles (NPs) with different spectral lights was carried out to unveil the effect of change in the wavelength of Photons. NPs were synthesized by co-precipitation technique exposed to different light regimes (dark environment, daylight, and colored lights (blue, green, yellow, and red) from light emitting diodes (LEDs) at room temperature. X-ray diffractogram (XRD) analysis revealed that the synthesized NPs were hematite (α-Fe2 O3) with rhombohedral structure while scanning electron microscopic (SEM) study demonstrate the spherical and nano-disk like surface morphology. An increase in the size of NPs from 20.61 nm to 28.87 nm was observed with the increase in the wavelength of light. The elemental composition and surface chemistry of NPs were studied from energy-dispersive x-ray diffractive (EDX) and Fourier transform infrared spectroscopy (FT-IR) spectra. Maximum free radical quenching activity and total antioxidant potential were found by red light synthesized NPs (13.72%, and 36.72 ± 1.06 µg AAE/mg, respectively). The dark environment synthesized NPs had the maximum reduction potential (20.20 ± 0.4 µg AAE/mg). The highest metal chelating and cation radical scavenging was observed by blue light (41.48%) and daylight (9.71%) synthesized NPs respectively. α-Fe2O3 NPs showed significant enzyme inhibitory effects on urease, lipase, and alpha-amylase. The NPs also exhibited intrinsic peroxidase-like activity. Green and red light synthesized α-Fe2O3 NPs displayed the strongest antibacterial activity (12 mm) against Methicillin-resistant Staphylococcus aureus, and Pseudomonas aeruginosa respectively. This study is considered a novel step toward the synthesis of hematite (α-Fe2O3) NPs under LEDs with specific physio-chemical and biological properties to be employed in biological, environmental, and agricultural fields.

Fabrication of 3D-printed hydroxyapatite using freeze-drying method for bone regeneration: RVE and finite element simulation analysis

Tissue engineering is an interdisciplinary approach that utilizes cells, scaffolds, and biofactors to develop biosynthetic bone scaffolds for bone regeneration applications. These scaffolds are three-dimensional porous structures with specific mechanical and biological properties that facilitate the attachment and proliferation of osteoinductive cells on their surfaces. In this study, bone scaffolds were 3D-printed using PLA material, and a variety of three-dimensional porous structures, including Kelvin, Octet truss, and Gibson Ashby, were employed. To improve the biological properties of the scaffolds, they were coated with alginate/hydroxyapatite using the Freeze-drying method. The Alginate/HA RVEs were analyzed under periodic boundary conditions, and the elastic modulus was found to improve from 100 MPa (pure alginate) to 149 MPa by adding 30 wt% HA particles. The mechanical properties of the scaffolds were investigated under compressive deformation using experiments and finite element simulations. The results show that the compressive strength of structures follows the order σOctettruss > σGibsonashby > σKelvin. The Freeze-drying process causes pore formation on the scaffold surface. According to the microstructural analysis, the pore size was observed for composite scaffolds approximately at 320–340 μm. After 21-day, most parts of the scaffold surface were coated by the apatite layer completely, and the surface of the pores was blocked by the apatite layer. To characterize cell viability, an MTT assay was used. The scaffolds expose high cell viability around 97% and did not show any significant toxicity.

KNOWLEDGE AND AWARENESS OF THE MEDICINE DISPOSAL AMONG HEALTHCARE PROFESSIONALS

Pharmaceutical active preparations are designed with specific biological and physiological properties. These formulations possess desired therapeutic action against numerous diseases and infections. But some preparations have hazardous effects on the environment when it comes to disposal of medicines, it is necessary to know about the importance of proper waste disposal. The primary objective of the study is to know about the importance of the medicinal waste disposal system and the awareness among health care professionals especially past expiry date. The cross-sectional survey-based study was performed in Karachi. Data was collected through an online Google questionnaire form. The results were analyzed. Among 203 responders, 65% (n=132) were females while the other 35% (n=71) were males. Approximately 57.1% (n=116) agreed that they are aware of the hazards and disposal of medication waste and 63.05% (n=128) think that it is the responsibility of Pharmacies Association and other regulatory bodies for awareness of proper disposal of medicines. The study recommends that we establish uniform guidelines for the safe disposal of expired or unused medications. Significant problems and malpractices were identified for unused, and unwanted prescription medication, lack of a drug take-back system, proper disposal of medications & surgical, inadequate awareness about disposal system adversely affecting our environment and health.

Superfoods and their role in disease prevention

Introduction and purpose Functional food also known by the term “superfoods” are rich in bioactive compounds with specific biological properties and due to that beneficial effects within the human body. Nowadays chronic degenerative diseases such as diabetes, cardiovascular disease, obesity and cancer are increasingly common in the population. Therefore the need to support treatment but also reduce the risk of these diseases in the first place increases as well. This is the reason for the great interest and growing trend in the consumption of superfoods, especially in Europe and the United States. The purpose of this article is to demonstrate the impact of selected superfoods on human health. State of knowledge Superfoods are considered nutrient-dense and rich in bioactive compounds that are beneficial for physical and mental health. Antioxidant activity is one of the most important properties for human health improvement. This activity is scavenging free radicals, thus preventing the development of various degenerative diseases. Today, more and more products are considered superfoods. Fruits, the examples of superfoods which will be discussed in this work, are well-available and require no heat treatment therefore incorporating them in one's diet seems to be an easy way to improve health as a consequence. Summary The potential beneficial role of superfoods is considered in health promotion and even preventing the development of diseases. However, this can only be possible if superfoods are part of a balanced diet and healthy lifestyle. The following article is a review of current knowledge and data available in publications in Pubmed and Google Scholar databases related to correlation between selected superfoods consumption and disease prevention.

Fabrication, Structural and Biological Characterization of Zinc-Containing Bioactive Glasses and Their Use in Membranes for Guided Bone Regeneration.

Polymeric membranes are widely used in guided bone regeneration (GBR), particularly in dentistry. In addition, bioactive glasses can be added to the polymers in order to develop a matrix that is osteoconductive and osteoinductive, increasing cell adhesion and proliferation. The bioactive glasses allow the insertion into its network of therapeutic ions in order to add specific biological properties. The addition of zinc into bioactive glasses can promote antibacterial activity and induce the differentiation and proliferation of the bone cells. In this study, bioactive glasses containing zinc (0.25, 0.5, 1 and 2 mol%) were developed and structurally and biologically characterized. The biological results show that the Zn-containing bioactive glasses do not present significant antibacterial activity, but the addition of zinc at the highest concentration does not compromise the bioactivity and promotes the viability of Saos-2 cells. The cell culture assays in the membranes (PCL, PCL:BG and PCL:BGZn2) showed that zinc addition promotes cell viability and an increase in alkaline phosphatase (ALP) production.

喀斯特石漠化锑矿区植物群落主要物种生态位特征及其种间联结

PDF HTML阅读 XML下载 导出引用 引用提醒 喀斯特石漠化锑矿区植物群落主要物种生态位特征及其种间联结 DOI: 10.5846/stxb202203300794 作者: 作者单位: 作者简介: 通讯作者: 中图分类号: 基金项目: 国家重点研发计划场地污染土壤成因与治理技术专项项目（2020YFC1807704） Niche characteristics and interspecific association of main plant species in antimony mining sites of karst rocky desertification area, Guizhou, China Author: Affiliation: Fund Project: 摘要 | 图/表 | 访问统计 | 参考文献 | 相似文献 | 引证文献 | 资源附件 | 文章评论 摘要:锑矿的开采等活动剥离了喀斯特石漠化区的地上植被，导致该区群落物种组成与结构被破坏、生态系统受损或功能丧失。为了解锑矿开采后生态破坏区优势物种亮叶桦（Betula luminifera）群落特征及演替状态，并为复层植被重建的物种选择提供理论依据。基于贵州晴隆大厂镇锑矿生态破坏区调查数据，分析了该区优势物种的Levins生态位宽度和Pianka生态位重叠度，并运用卡方检验（χ2）、Ochiai指数（OI）和Pearson相关性计算了群落优势物种种间联结性。结果表明：（1）石漠化锑矿生态破坏区物种组成远低于未破坏区（30科53属68种），仅为14科18属22种，乔木层物种仅为亮叶桦，灌木层物种重要值由高到低依次为密蒙花（Buddleja officinalis）、茅莓（Rubus parvifolius）和水麻（Boehmeria penduliflora）等，草本层物种重要值由高到低依次为芒（Miscanthus sinensis）、头花蓼（Polygonum capitatum）、破坏草（Ageratina adenophora）、艾草（Artemisia argyi）和鬼针草（Bidens pilosa）等。（2）锑矿生态破坏区灌草层和未破坏区乔灌草层的物种重要值与生态位宽度呈极显著正相关，但不同物种的生态位宽度不同，这是物种生物学属性不同所致；锑矿生态破坏区除水麻与插田泡（Rubus coreanus）的生态位重叠值为1外，其他物种间的生态位重叠程度较低。（3）石漠化锑矿生态破坏区灌木层总体呈显著负联结，种对间负联结数占比较高（5对）；草本层总体联结性不显著，但种对间负联结数有15对，其中艾草与芒、艾草与白三叶（Trifolium repens）、芒与破坏草种对间联结程度较高，表明植被群落处于演替前期，极不稳定且易受破坏。未破坏区乔木层和灌木层总体联结性不显著，草本层总体为显著正联结，表明未破坏区植被群落相对稳定。（4）石漠化锑矿生态破坏区植被恢复应选择生态习性相近、重叠程度较小、种间为正联结的物种，例如乔本层的亮叶桦和山苍子（Litsea cubeba）等，灌木层的密蒙花和茅莓等，草本层的艾草、蕨（Pteridium aquilinum）、芒和马唐（Digitaria sanguinalis）等，以达到乔灌草配置具有高稳定性植物群落的效果。锑矿生态破坏区物种组成较少，植物群落结构不稳定，处于演替早期；未来喀斯特石漠化锑矿生态破坏区植物群落仍需要很长一段时间演替才能达到未破坏区植物群落状态，适宜的乡土植物和合理的配置模式有助于加快植被恢复进程。 Abstract:The plant community was damaged or stripped by antimony (Sb) mining activities in the karst rocky desertification of Guizhou, China, which destroyed the species composition and structure of the community, damaged the function of this ecosystem. This study aims to well understand the actual vegetation, community characteristics and succession stage of the community with dominant species Betula luminifera in the Sb mining area, and provide the theoretical basis for revegetation and ecological rehabilitation. After the field investigation dataset of the ecological damaged area by Sb mining and control areas, the Levins's and Pianka's method were applied to evaluate the niche width of species, the interspecific niche overlap, and the interspecific associations were assessed by the chi-square test (χ2), Ochiai index (OI) and Pearson correlation. The results show that (1) there is only 14 families, 18 genera and 22 species in the ecological damaged area by Sb mining, which is lower than that of the undamaged area of control, with 30 families, 53 genera and 68 species. The only tree species is Betula luminifera, the shrubs layer species with top three importance values (IV) are Buddleja officinalis, Rubus parvifolius, Boehmeria penduliflora, and the herb layer with top five IV are Miscanthus sinensis, Polygonum capitatum, Ageratina Adenophora, Artemisia argyi and Bidens Pilosa in the ecological damaged area by Sb mining. (2) There are significantly positive between IV and niche width of species in the shrub-herb layer of Sb mining area and the layer of control area, while the niche width of different species shows inconsistence, which may be ascribed to the specific biological properties of the different species. Except for the niche overlap between Rubus coreanus and B. penduliflora is 1 in the Sb mining area, the niche overlap of others interspecies are low. (3) The main species of shrub layer in Sb mining area of karst rocky desertification has a significantly negative association, and the species pairs of negative associations are relatively high (5 pairs). The main species of herb layer of Sb mining area has no significant association, while high association values are observed between A. argyi and M. sinensis, A. argyi and Trifolium repens, T. repens and Ageratina Adenophora. It suggested the community at the early succession with extremely unstable stage. In the control area, the main species of tree and shrub layer show no significant associations, the main species of herb layer indicates the significantly positive association, indicating that the community is at relatively stable stage. (4) The results suggest that ideal plant candidates are the species with similar ecological habits, low niche overlap, and positive interspecific association for the purpose of Sb mining area revegetation, such as B. luminifera, Litsea cubeba, B. officinalis, R. parvifolius, A. argyi, Pteridium aquilinum, M. sinensis and Digitaria sanguinalis. It will help to construct the plant community with high stability of multiple stratified of trees, shrubs and herbs. Taken together, the plant community in Sb mining area characterized with low species composition, and unstable plant community, and an early stage of succession. It will take a long time for rebuilding the stable plant community in the Sb mining area, and the suitable native plant application and vegetation arrangement during the ecological rehabilitation help to facilitate the revegetation and sucession. 参考文献 相似文献 引证文献

Long non coding RNA in osteoporosis

Osteoporosis (OP) is the most common skeletal disease, caused by a lack of balance between osteoclast and osteoblast activity. This results in erosion overriding the deposition of new bone matrix, consequently leading to low-quality bone and an increased risk of incurring fragility fractures. Dual energy X-ray absorptiometry is the gold standard for the diagnosis of OP, while anti-osteoporotic drugs are the gold standard for its treatment. However, due to limitations to their use, researchers have turned to epigenetics as a substantial source of molecules that could potentially be used as diagnostic, prognostic, and therapeutic biomarkers for OP. In particular, long non-coding RNAs (lncRNAs) possess special biological properties that could open new horizons in the field of personalized medicine. This mini review seeks to offer an overview of the studies carried out in the last year on the different lncRNAs that could be involved in the pathogenesis of OP and that could pave the way for the development of innovative therapeutic strategies for this disease.

Green approaches for extraction, chemical modification and processing of marine polysaccharides for biomedical applications.

Over the past few decades, natural-origin polysaccharides have received increasing attention across different fields of application, including biomedicine and biotechnology, because of their specific physicochemical and biological properties that have afforded the fabrication of a plethora of multifunctional devices for healthcare applications. More recently, marine raw materials from fisheries and aquaculture have emerged as a highly sustainable approach to convert marine biomass into added-value polysaccharides for human benefit. Nowadays, significant efforts have been made to combine such circular bio-based approach with cost-effective and environmentally-friendly technologies that enable the isolation of marine-origin polysaccharides up to the final construction of a biomedical device, thus developing an entirely sustainable pipeline. In this regard, the present review intends to provide an up-to-date outlook on the current green extraction methodologies of marine-origin polysaccharides and their molecular engineering toolbox for designing a multitude of biomaterial platforms for healthcare. Furthermore, we discuss how to foster circular bio-based approaches to pursue the further development of added-value biomedical devices, while preserving the marine ecosystem.

Green Synthesis of Silver Nanoparticles from Bark Extract of Terminalia arjuna and their Application as Next Generation Antibacterial Agents

Background: The antimicrobial properties of silver can be enhanced in the form of silver nanoparticles due to their specific physical, chemical, and biological properties, thus enabling their use in different antibacterial applications against antibiotic-resistant bacteria. Objectives: Present study was planned to evaluate the antibacterial activity of silver nanoparticles synthesized from bark extract of Terminalia arjuna. Methods: Silver nanoparticles were synthesized using 80% methanolic extract of Terminalia arjuna bark, followed by their characterization using UV-Visible spectroscopy, particle size analysis, and atomic force microscopy. The antibacterial activity of synthesized silver nanoparticles was analyzed against Escherichia coli MTCC1687, Pseudomonas aeruginosa ATCC9027, and Staphylococcus aureus ATCC6538. Results: The silver nanoparticles were observed to inhibit microbial growth in a concentrationdependent manner (2-0.5mg/mL), and the cell death was confirmed using fluorescent microscopy. Conclusion: The antibacterial activity of these nanoparticles suggests that the synthesized nanoparticles can be used to treat bacterial infections of the skin.

In Vivo Analysis of a Biomolecular Condensate in the Nervous System of C. elegans.

Liquid-liquid phase separation (LLPS) has emerged as a common biophysical event that facilitates the formation of non-membrane-bound cellular compartments, also termed biomolecular condensates. Since the first report of a biomolecular condensate in the germline of C. elegans, many regulatory hubs have been shown to have similar liquid-like features. With the wealth of molecules now being reported to possess liquid-like features, an impetus has been placed on reconciling LLPS with regulation of specific biological properties in vivo. Herein, we report a methodology used to study LLPS-associated features in C. elegans neurons, illustrated using the RNA granule protein TIAR-2. In axons, TIAR-2 forms liquid-like granules, which following injury are inhibitory to the regeneration process. Measuring the dynamics of TIAR-2 granules provides a tractable biological output to study LLPS function. In conjunction with other established methods to assess LLPS, the results from the protocol outlined provide comprehensive insight regarding this important biophysical property.

Ultra-high-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flightmass spectrometryand molecular networking analysis to investigate the chemodiversity of bioactive extracts of Annona jahnii Saff. fungi from the Brazilian Amazon.

Annona species are of interest for the isolation of bioactive molecules; however, studies of Annona jahnii Saff. are limited. The exploration of bioactive metabolites of endophytes isolated from this species is unprecedented and allows the preservation of the host plant, in addition to enabling the discovery of compounds with promising biological activities. Ethyl acetate extracts from the cultured media of five fungi were obtained. The antioxidant capacity of the extracts was measured using the 1,1-diphenyl-2-picrylhydrazyl free radical method. Antimicrobial activity was determined using the microdilution method in broth in 96-well plates. The exploration of the metabolic profile of the extracts and dereplication of the compounds were performed using ultra-high-performance liquid chromatography/electrospray ionization/tandem mass spectrometry (UHPLC/ESI-MS/MS) combined with analysis using molecular networking (MN). A total of 1818 MS features were detected in the five selected extracts, of which 39 compounds were putatively identified. The secondary metabolites with the highest abundance were alkaloids, naphthopyrons, and cytochalasins. Other secondary metabolites include fumonisins, coumarin, and a meroterpenoid. Most of these compounds are related to specific biological properties such as antioxidant, anti-inflammatory, antimicrobial, antiviral, and antitumor activities. Extracts F398 and F403 showed inhibitory activity of the four pathogens tested. Extracts F475 and F506 did not inhibit the growth of Staphylococcus aureus, and F407 did not inhibit the growth of Escherichia coli in addition to having potent antioxidant activity, with IC50 values of 10μg/mL or less. The use of UHPLC/ESI-MS/MS data combined with MN proved useful in the dereplication of bioactive molecules of complex extracts that are still unexplored. These initial investigations should significantly assist in further research and increase the efficiency and speed in the discovery of new sources of secondary metabolites and new natural products.

Antibacterial, Antifungal, Antiviral, and Antiparasitic Activities of Peganum harmala and Its Ingredients: A Review.

Infectious diseases have always been the number one enemy threatening health and well-being. With increasing numbers of infectious diseases, growing resistance of pathogens, and declining roles of antibiotics in the treatment of infectious diseases, it is becoming increasingly difficult to treat new infectious diseases, and there is an urgent need to develop new antibiotics to change the situation. Natural products tend to exhibit many special biological properties. The genus Peganum (Zygophyllaceae) has been used, for a long time, to treat cough, asthma, lumbago, hypertension, diabetes, and Alzheimer’s disease. Over the past two decades, a growing number of studies have shown that components from Peganum harmala Linn and its derivatives can inhibit a variety of microorganisms by inducing the accumulation of ROS in microorganisms, damaging cell membranes, thickening cell walls, disturbing cytoplasm, and interfering with DNA synthesis. In this paper, we provide a review on the antibacterial, antifungal, antiviral, and antiparasitic activities of P. harmala, with a view to contribute to research on utilizing P. harmala for medicinal applicaitons and to provide a reference in the field of antimicrobial and a basis for the development of natural antimicrobial agents for the treatment of infectious diseases.

Development of chimeric forms of the matrix metalloproteinase 2 collagen binding domain as artificial membrane binding proteins for targeting stem cells to cartilage lesions in osteoarthritic joints

Targeting stem cells to cartilage lesions has the potential to enhance engraftment and chondrogenesis. Denatured type II collagen fibrils (gelatin) are exposed in lesions at the surface of osteoarthritic articular cartilage and are therefore ideal target sites. We have designed and investigated chimeric mutants of the three modules of the MMP-2 collagen binding domain (CBD) as potential ligands for stem cell targeting. We expressed full-length CBD for the first time and used it to identify the most important amino acid residues for binding to gelatin. Module 2 of CBD had the highest affinity binding to both Type I and Type II gelatin, whereas module 1 showed specificity for type II gelatin and module 3 for type I gelatin. We went on to generate chimeric forms of CBD consisting of three repeats of module 1 (111), module 2 (222) or module 3 (333). 111 lacked solubility and could not be further characterised. However 222 was found to bind to type II gelatin 14 times better than CBD, suggesting it would be optimal for attachment to cartilage lesions, whilst 333 was found to bind to type I gelatin 12 times better than CBD, suggesting it would be optimal for attachment to lesions in type I collagen-rich tissues. We coated 222 onto the external membrane of Mesenchymal Stem Cells and demonstrated higher attachment of the coated cells to type II gelatin than uncoated cells. We conclude that the three modules of CBD each have specific biological properties that can be exploited for targeting stem cells to cartilage lesions and other pathological sites.

Impact of Indazole Scaffold as Antibacterial and Antifungal Agent.

Heterocycles consisting of a nitrogen atom, Indazole, is a pungent, biological, heterocyclic, bicyclic compound possessing electron-rich portions. Indazole is composed of two nitrogen atoms put under the azoles family, further called isoindazolone. It is colorless solid nitrogen- containing heterocyclics with atomic formula-C7H6N2 are extraordinary scaffolds, still identified as isoindazole. Therefore, analogs of Indazole have experienced expert approaches in later times because of its special biological properties, such as anti-microbial, anti-inflammatory, anticancer, anti- HIV and antihypertensive actions. 1H-indazole and 2H-indazole are two toutomeric forms of Indazole. Sometimes, indazole produces three tautomeric forms that are 1H, 2H and 3H tautomers of indazole. 1H-indazole is reliable than 2H-indazole. We should note that a series of derivatives of indazole having 2H toutomers follow hybridization of cyclic systems and act as anti-inflammatory as well as anti-microbial compounds. It formed Indazole itself and derivatives of Indazole in natural products. A sequence of N-methyl-3-aryl inazoles has dominant against bacterial strains like xanthomon as campstris, Baillus cereus, Escherichia coli, Bacillus megaterium and a fungal strain candida albicans found by in-vitro anti-microbial study of indazole derivatives.

Heme oxygenase‐1 induction by gallic acid‐ g ‐chitosan is an important event in modulating adipocyte differentiation

Obesity, one of the common worldwide chronic health diseases co-relates with adipogenesis. Adipogenesis is a complex biological action of the emergence of mature adipocytes from the differentiation of pre-adipocytes and the disfunction of this process leads to the development of metabolic issues in obesity. Recently, much attention has been paid to utilizing natural compounds to discover their biological activities. This study focused on investigating the probable anti-adipogenic effects of gallic acid-g-chitosan (GAC) and plain chitosan (PC) through regulating the heme oxygenase-1 (HO-1)/Nrf2 pathway on mesenchymal stem cells. Gallic acid is grafted onto the PC backbone to improve its specific physical and biological properties. GAC showed promising anti-adipogenic effects by enhancing HO-1 expression and lipolysis and as well as suppressing lipid accumulation, reactive oxygen species, and pro-inflammatory cytokines production, transcription factor expression compared to the PC treatment. On the contrary, zinc protoporphyrin ІX (ZnPP), a HO-1 inhibitor reversed these effects of GAC on adipogenesis. Taken all together, this study revealed that grafting GA onto the chitosan improved potential anti-adipogenic activity by induction of the HO-1/Nrf2 pathway on mesenchymal stem cells (MSCs). PRACTICAL APPLICATIONS: GAC is a well-known copolymer with versatile bioactivities such as antimicrobial, antioxidant, and anti-diabetic activity. However, the anti-adipogenic effect of GAC has not been explored in MSCs. This study demonstrated that GAC inhibited adipocyte differentiation in MSCs through HO-1 activation. These findings suggest that GAC can be applied practically from different perspectives. GAC can be applied in the pharmacological industry to the development of anti-obesity drugs, medicinal perspectives for the treatment of obesity and obesity-related diseases, and in the food industry as a functional food to promote health and decrease the risk of diseases.

Eosinophilic granulomatosis with polyangitis: A new target for biologicals.

Eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome) is a rare systemic necrotizing granulomatous vasculitis in the spectrum of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Nevertheless, EGPA has specific clinical, biological and histological properties different from other AAVs [microscopic polyangiitis (MPA) and granulomatous polyangiitis (GPA)]. Recently, thanks to the studies conducted to understand the pathophysiology of EGPA, unlike neutrophils in other AAVs, the main cells involved in EGPA have been observed to be eosinophils. The key role of eosinophils in EGPA and recent development of targeted agents to treat other eosinophil-related diseases have created new therapeutic opportunities for EGPA. Conventional treatment of EGPA relies mainly on agents that decrease inflammation. Cornerstone therapy is systemic glucocorticoids, used as monotherapy or in combination with immunosuppressive agents. However, new therapeutic approaches are needed especially for persistent asthma symptoms, refractory disease, relapses and problems associated with corticosteroid dependence. Recently, the first large-scale randomized controlled clinical trial on polyangiitis and eosinophilic granulomatosis has demonstrated the efficacy of eosinophil-targeted biotherapy anti-interleukin-5 (IL-5) mepolizumab, and is approved for the management of EGPA. This finding opens a new era for EGPA management. This review provides an overview of eosinophilic granulomatosis with polyangiitis in the light of new targeted biological therapies.

The spectrum of building block conformers sustains the biophysical properties of clinically-oriented self-assembling protein nanoparticles

Histidine-rich peptides confer self-assembling properties to recombinant proteins through the supramolecular coordination with divalent cations. This fact allows the cost-effective, large-scale generation of microscopic and macroscopic protein materials with intriguing biomedical properties. Among such materials, resulting from the simple bioproduction of protein building blocks, homomeric nanoparticles are of special value as multivalent interactors and drug carriers. Interestingly, we have here identified that the assembly of a given His-tagged protein might render distinguishable categories of self-assembling protein nanoparticles. This fact has been scrutinized through the nanobody-containing fusion proteins EM1-GFP-H6 and A3C8-GFP-H6, whose biosynthesis results in two distinguishable populations of building blocks. In one of them, the assembling and disassembling is controllable by cations. However, a second population immediately self-assembles upon purification through a non-regulatable pathway, rendering larger nanoparticles with specific biological properties. The structural analyses of both model proteins and nanoparticles revealed important conformational variability in the building blocks. This fact renders different structural and functional categories of the final soft materials resulting from the participation of energetically unstable intermediates in the oligomerization process. These data illustrate the complexity of the Hismediated protein assembling in recombinant proteins but they also offer clues for a better design and refinement of protein-based nanomedicines, which, resulting from biological fabrication, show an architectonic flexibility unusual among biomaterials.

How Molecular Topology Can Help in Amyotrophic Lateral Sclerosis (ALS) Drug Development: A Revolutionary Paradigm for a Merciless Disease.

Even if amyotrophic lateral sclerosis is still considered an orphan disease to date, its prevalence among the population is growing fast. Despite the efforts made by researchers and pharmaceutical companies, the cryptic information related to the biological and physiological onset mechanisms, as well as the complexity in identifying specific pharmacological targets, make it almost impossible to find effective treatments. Furthermore, because of complex ethical and economic aspects, it is usually hard to find all the necessary resources when searching for drugs for new orphan diseases. In this context, computational methods, based either on receptors or ligands, share the capability to improve the success rate when searching and selecting potential candidates for further experimentation and, consequently, reduce the number of resources and time taken when delivering a new drug to the market. In the present work, a computational strategy based on Molecular Topology, a mathematical paradigm capable of relating the chemical structure of a molecule to a specific biological or pharmacological property by means of numbers, is presented. The result was the creation of a reliable and accessible tool to help during the early in silico stages in the identification and repositioning of potential hits for ALS treatment, which can also apply to other orphan diseases. Considering that further computational and experimental results will be required for the final identification of viable hits, three linear discriminant equations combined with molecular docking simulations on specific proteins involved in ALS are reported, along with virtual screening of the Drugbank database as a practical example. In this particular case, as reported, a clinical trial has been already started for one of the drugs proposed in the present study.

Functional Graphene Nanomaterials-Based Hybrid Scaffolds for Osteogenesis and Chondrogenesis.

With the emerging trends and recent advances in nanotechnology, it has become increasingly possible to overcome current hurdles for bone and cartilage regeneration. Among the wide type of nanomaterials, graphene (G) and its derivatives (graphene-based materials, GBMs) have been highlighted due to the specific physicochemical and biological properties. In this review, we present the recent development of GBM-based scaffolds for bone and cartilage engineering, focusing on the formulation/shape/size-dependent characteristics, types of scaffold and modification, biocompatibility, bioactivity and underlying mechanism, drawback and prospect of each study. From the findings described herein, mechanical property, biocompatibility, osteogenic and chondrogenic property of GBM-based scaffolds could be significantly enhanced through various scaffold fabrication methods and conjugation with polymers/nanomaterials/drugs. In conclusion, the results presented in this review support the promising prospect of using GBM-based scaffolds for improved bone and cartilage tissue engineering. Although GBM-based scaffolds have some limitations to be overcome by future research, we expect further developments to provide innovative results and improve their clinical potential for bone and cartilage regeneration.

Ongoing Challenges to Develop High Concentration Monoclonal Antibody-based Formulations for Subcutaneous Administration: Quo Vadis?

Although many subcutaneously (s.c.) delivered, high-concentration antibody formulations (HCAF) have received regulatory approval and are widely used commercially, formulation scientists are still presented with many ongoing challenges during HCAF development with new mAb and mAb-based candidates. Depending on the specific physicochemical and biological properties of a particular mAb-based molecule, such challenges vary from pharmaceutical attributes e.g., stability, viscosity, manufacturability, to clinical performance e.g., bioavailability, immunogenicity, and finally to patient experience e.g., preference for s.c. vs. intravenous delivery and/or preferred interactions with health-care professionals. This commentary focuses on one key formulation obstacle encountered during HCAF development: how to maximize the dose of the drug? We examine methodologies for increasing the protein concentration, increasing the volume delivered, or combining both approaches together. We discuss commonly encountered hurdles, i.e., physical protein instability and solution volume limitations, and we provide recommendations to formulation scientists to facilitate their development of s.c. administered HCAF with new mAb-based product candidates.