Neuroprotection for Stroke: Current Status and Future Perspectives

Neuroprotection aims to prevent salvageable neurons from dying. Despite showing efficacy in experimental stroke studies, the concept of neuroprotection has failed in clinical trials. Reasons for the translational difficulties include a lack of methodological agreement between preclinical and clinical studies and the heterogeneity of stroke in humans compared to homogeneous strokes in animal models. Even when the international recommendations for preclinical stroke research, the Stroke Academic Industry Roundtable (STAIR) criteria, were followed, we have still seen limited success in the clinic, examples being NXY-059 and haematopoietic growth factors which fulfilled nearly all the STAIR criteria. However, there are a number of neuroprotective treatments under investigation in clinical trials such as hypothermia and ebselen. Moreover, promising neuroprotective treatments based on a deeper understanding of the complex pathophysiology of ischemic stroke such as inhibitors of NADPH oxidases and PSD-95 are currently evaluated in preclinical studies. Further concepts to improve translation include the investigation of neuroprotectants in multicenter preclinical Phase III-type studies, improved animal models, and close alignment between clinical trial and preclinical methodologies. Future successful translation will require both new concepts for preclinical testing and innovative approaches based on mechanistic insights into the ischemic cascade.     

Current Status and Future Perspectives of Mass Spectrometry Imaging

Mass spectrometry imaging is employed for mapping proteins, lipids and metabolites in biological tissues in a morphological context. Although initially developed as a tool for biomarker discovery by imaging the distribution of protein/peptide in tissue sections, the high sensitivity and molecular specificity of this technique have enabled its application to biomolecules, other than proteins, even in cells, latent finger prints and whole organisms. Relatively simple, with no requirement for labelling, homogenization, extraction or reconstitution, the technique has found a variety of applications in molecular biology, pathology, pharmacology and toxicology. By discriminating the spatial distribution of biomolecules in serial sections of tissues, biomarkers of lesions and the biological responses to stressors or diseases can be better understood in the context of structure and function. In this review, we have discussed the advances in the different aspects of mass spectrometry imaging processes, application towards different disciplines and relevance to the field of toxicology.     

Buckwheat in Tissue Culture Research: Current Status and Future Perspectives

Buckwheat is a member of a genus of 23 species, where the two most common species are Fagopyrum esculentum (common buckwheat) and Fagopyrum tataricum (Tartary buckwheat). This pseudocereal is a source of micro and macro nutrients, such as gluten-free proteins and amino acids, fatty acids, bioactive compounds, dietary fibre, fagopyrins, vitamins and minerals. It is gaining increasing attention due to its health-promoting properties. Buckwheat is widely susceptible to in vitro conditions which are used to study plantlet regeneration, callus induction, organogenesis, somatic embryogenesis, and the synthesis of phenolic compounds. This review summarises the development of buckwheat in in vitro culture and describes protocols for the regeneration of plantlets from various explants and differing concentrations of plant growth regulators. It also describes callus induction protocols as well as the role of calli in plantlet regeneration. Protocols for establishing hairy root cultures with the use of Agrobacterium rhizogens are useful in the synthesis of secondary metabolites, as well as protocols used for transgenic plants. The review also focuses on the future prospects of buckwheat in tissue culture and the challenges researchers are addressing.     

Molecular Basis of Endometriosis and Endometrial Cancer: Current Knowledge and Future Perspectives

The human endometrium is a unique tissue undergoing important changes through the menstrual cycle. Under the exposure of different risk factors in a woman’s lifetime, normal endometrial tissue can give rise to multiple pathologic conditions, including endometriosis and endometrial cancer. Etiology and pathophysiologic changes behind such conditions remain largely unclear. This review summarizes the current knowledge of the pathophysiology of endometriosis and its potential role in the development of endometrial cancer from a molecular perspective. A better understanding of the molecular basis of endometriosis and its role in the development of endometrial pathology will improve the approach to clinical management.     

Anti-Angiogenic Therapy: Current Challenges and Future Perspectives

Anti-angiogenic therapy is an old method to fight cancer that aims to abolish the nutrient and oxygen supply to the tumor cells through the decrease of the vascular network and the avoidance of new blood vessels formation. Most of the anti-angiogenic agents approved for cancer treatment rely on targeting vascular endothelial growth factor (VEGF) actions, as VEGF signaling is considered the main angiogenesis promotor. In addition to the control of angiogenesis, these drugs can potentiate immune therapy as VEGF also exhibits immunosuppressive functions. Despite the mechanistic rational that strongly supports the benefit of drugs to stop cancer progression, they revealed to be insufficient in most cases. We hypothesize that the rehabilitation of old drugs that interfere with mechanisms of angiogenesis related to tumor microenvironment might represent a promising strategy. In this review, we deepened research on the molecular mechanisms underlying anti-angiogenic strategies and their failure and went further into the alternative mechanisms that impact angiogenesis. We concluded that the combinatory targeting of alternative effectors of angiogenic pathways might be a putative solution for anti-angiogenic therapies.     

Enzyme Therapy: Current Challenges and Future Perspectives

In recent years, enzymes have risen as promising therapeutic tools for different pathologies, from metabolic deficiencies, such as fibrosis conditions, ocular pathologies or joint problems, to cancer or cardiovascular diseases. Treatments based on the catalytic activity of enzymes are able to convert a wide range of target molecules to restore the correct physiological metabolism. These treatments present several advantages compared to established therapeutic approaches thanks to their affinity and specificity properties. However, enzymes present some challenges, such as short in vivo half-life, lack of targeted action and, in particular, patient immune system reaction against the enzyme. For this reason, it is important to monitor serum immune response during treatment. This can be achieved by conventional techniques (ELISA) but also by new promising tools such as microarrays. These assays have gained popularity due to their high-throughput analysis capacity, their simplicity, and their potential to monitor the immune response of patients during enzyme therapies. In this growing field, research is still ongoing to solve current health problems such as COVID-19. Currently, promising therapeutic alternatives using the angiotensin-converting enzyme 2 (ACE2) are being studied to treat COVID-19.     

蛋白质体外折叠技术研究现状与展望

蛋白质折叠技术是生物工程的新“单元操作”。本文阐述了蛋白质体外折叠研究的重要理论意义和应用价值，综述了目前蛋白质体外折叠技术研究进展，最后对蛋白质折叠技术的研究进行了展望。     

Immunotherapy in Glioblastoma: Current Approaches and Future Perspectives

Glioblastoma (GBM) is the most common malignant brain tumor. Despite multimodality treatment with surgical resection, radiation therapy, chemotherapy, and tumor treating fields, recurrence is universal, median observed survival is low at 8 months and 5-year overall survival is poor at 7%. Immunotherapy aims to generate a tumor-specific immune response to selectively eliminate tumor cells. In treatment of GBM, immunotherapy approaches including use of checkpoint inhibitors, chimeric antigen receptor (CAR) T-Cell therapy, vaccine-based approaches, viral vector therapies, and cytokine-based treatment has been studied. While there have been no major breakthroughs to date and broad implementation of immunotherapy for GBM remains elusive, multiple studies are underway. In this review, we discuss immunotherapy approaches to GBM with an emphasis on molecularly informed approaches.     

Noninvasive Diagnostics of Renal Amyloidosis: Current State and Perspectives

Amyloidoses is a group of diseases characterized by the accumulation of abnormal proteins (called amyloids) in different organs and tissues. For systemic amyloidoses, the disease is related to increased levels and/or abnormal synthesis of certain proteins in the organism due to pathological processes, e.g., monoclonal gammopathy and chronic inflammation in rheumatic arthritis. Treatment of amyloidoses is focused on reducing amyloidogenic protein production and inhibition of its aggregation. Therapeutic approaches critically depend on the type of amyloidosis, which underlines the importance of early differential diagnostics. In fact, the most accurate diagnostics of amyloidosis and its type requires analysis of a biopsy specimen from the disease-affected organ. However, absence of specific symptoms of amyloidosis and the invasive nature of biomaterial sampling causes the late diagnostics of these diseases, which leads to a delayed treatment, and significantly reduces its efficacy and patient survival. The establishment of noninvasive diagnostic methods and discovery of specific amyloidosis markers are essential for disease detection and identification of its type at earlier stages, which enables timely and targeted treatment. This review focuses on current approaches to the diagnostics of amyloidoses, primarily with renal involvement, and research perspectives in order to design new specific tests for early diagnosis.     

The Genetic Architecture of Vascular Anomalies: Current Data and Future Therapeutic Perspectives Correlated with Molecular Mechanisms

Vascular anomalies (VAs) are morphogenesis defects of the vascular system (arteries, capillaries, veins, lymphatic vessels) singularly or in complex combinations, sometimes with a severe impact on the quality of life. The progress made in recent years with the identification of the key molecular pathways (PI3K/AKT/mTOR and RAS/BRAF/MAPK/ERK) and the gene mutations that lead to the appearance of VAs has allowed the deciphering of their complex genetic architecture. Understanding these mechanisms is critical both for the correct definition of the phenotype and classification of VAs, as well as for the initiation of an optimal therapy and the development of new targeted therapies. The purpose of this review is to present in synthesis the current data related to the genetic factors involved in the etiology of VAs, as well as the possible directions for future research. We analyzed the data from the literature related to VAs, using databases (Google Scholar, PubMed, MEDLINE, OMIM, MedGen, Orphanet) and ClinicalTrials.gov. The obtained results revealed that the phenotypic variability of VAs is correlated with genetic heterogeneity. The identification of new genetic factors and the molecular mechanisms in which they intervene, will allow the development of modern therapies that act targeted as a personalized therapy. We emphasize the importance of the geneticist in the diagnosis and treatment of VAs, as part of a multidisciplinary team involved in the management of VAs.     

Understanding Drivers of Ocular Fibrosis: Current and Future Therapeutic Perspectives

Ocular fibrosis leads to severe visual impairment and blindness worldwide, being a major area of unmet need in ophthalmology and medicine. To date, the only available treatments are antimetabolite drugs that have significant potentially blinding side effects, such as tissue damage and infection. There is thus an urgent need to identify novel targets to prevent/treat scarring and postsurgical fibrosis in the eye. In this review, the latest progress in biological mechanisms underlying ocular fibrosis are discussed. We also summarize the current knowledge on preclinical studies based on viral and non-viral gene therapy, as well as chemical inhibitors, for targeting TGFβ or downstream effectors in fibrotic disorders of the eye. Moreover, the role of angiogenetic and biomechanical factors in ocular fibrosis is discussed, focusing on related preclinical treatment approaches. Moreover, we describe available evidence on clinical studies investigating the use of therapies targeting TGFβ-dependent pathways, angiogenetic factors, and biomechanical factors, alone or in combination with other strategies, in ocular tissue fibrosis. Finally, the recent progress in cell-based therapies for treating fibrotic eye disorders is discussed. The increasing knowledge of these disorders in the eye and the promising results from testing of novel targeted therapies could offer viable perspectives for translation into clinical use.     

含碳浇注料的现状及展望

对克服妨碍含碳浇注料的发展及应用的主要技术难题所采取的措施进行了讨论。碳的可润湿性和分散性可通过涂覆材料来加以改进，诸如：碳化物（SiC)和氧化物（Al2O3、TiO2、SiO2、MgO、ZrO2)或形成微粒／小球粒。无裂纹致密涂覆层不仅改进了碳的可润湿性和分散性，还提高了抗氧化能力。致密的微粒或小球粒可以使基质中的碳达到均匀分布，同时获得满意的机械强度和抗侵蚀性。涂覆技术也已经用来改进铝质抗氧化剂的抗水化性，但在这一领域还需进行详细研究。目前使用的结合剂系统主要基于超细硅烟和水合氧化铝，因为它们在浇注料中不形成低熔点相。在研究现存涂覆技术和微粒／小球粒制备技术的同时，还将继续探寻新的加碳方法，并开始研究浇注方式、干燥和加热制度。     

Biological Detoxification of Mycotoxins: Current Status and Future Advances

Mycotoxins are highly toxic metabolites produced by fungi that pose a huge threat to human and animal health. Contamination of food and feed with mycotoxins is a worldwide issue, which leads to huge financial losses, annually. Decades of research have developed various approaches to degrade mycotoxins, among which the biological methods have been proved to have great potential and advantages. This review provides an overview on the important advances in the biological removal of mycotoxins over the last decade. Here, we provided further insight into the chemical structures and the toxicity of the main mycotoxins. The innovative strategies including mycotoxin degradation by novel probiotics are summarized in an in-depth discussion on potentialities and limitations. We prospected the promising future for the development of multifunctional approaches using recombinant enzymes and microbial consortia for the simultaneous removal of multiple mycotoxins.     

Liver Transplantation for Colorectal Liver Metastases: Current Management and Future Perspectives

Patients with nonresectable liver metastases from colorectal cancer have few therapeutic options and a dismal prognosis. Although liver transplantation for this indication has historically a poor reputation, recent advances in the field of chemotherapy and immunosuppression have paved the way to revisit the concept. New data have shown promising results that need to be validated in several ongoing clinical trials. Since liver grafts represent a scarce resource, several new tools are being explored to expand the donor pool for this indication. The purpose of this review is to present all current available data and perspectives about liver transplantation for nonresectable liver metastases from colorectal cancer.     

Peptides to Tackle Leishmaniasis: Current Status and Future Directions

Peptide-based drugs are an attractive class of therapeutic agents, recently recognized by the pharmaceutical industry. These molecules are currently being used in the development of innovative therapies for diverse health conditions, including tropical diseases such as leishmaniasis. Despite its socioeconomic influence on public health, leishmaniasis remains long-neglected and categorized as a poverty-related disease, with limited treatment options. Peptides with antileishmanial effects encountered to date are a structurally heterogeneous group, which can be found in different natural sources—amphibians, reptiles, insects, bacteria, marine organisms, mammals, plants, and others—or inspired by natural toxins or proteins. This review details the biochemical and structural characteristics of over one hundred peptides and their potential use as molecular frameworks for the design of antileishmanial drug leads. Additionally, we detail the main chemical modifications or substitutions of amino acid residues carried out in the peptide sequence, and their implications in the development of antileishmanial candidates for clinical trials. Our bibliographic research highlights that the action of leishmanicidal peptides has been evaluated mainly using in vitro assays, with a special emphasis on the promastigote stage. In light of these findings, and considering the advances in the successful application of peptides in leishmaniasis chemotherapy, possible approaches and future directions are discussed here.     

Molecular Pathogenesis of Glioblastoma in Adults and Future Perspectives: A Systematic Review

Glioblastoma (GBM) is the most common and malignant tumour of the central nervous system. Recent appreciation of the heterogeneity amongst these tumours not only changed the WHO classification approach, but also created the need for developing novel and personalised therapies. This systematic review aims to highlight recent advancements in understanding the molecular pathogenesis of the GBM and discuss related novel treatment targets. A systematic search of the literature in the PubMed library was performed following the PRISMA guidelines for molecular pathogenesis and therapeutic advances. Original and meta-analyses studies from the last ten years were reviewed using pre-determined search terms. The results included articles relevant to GBM development focusing on the aberrancy in cell signaling pathways and intracellular events. Theragnostic targets and vaccination to treat GBM were also explored. The molecular pathophysiology of GBM is complex. Our systematic review suggests targeting therapy at the stemness, p53 mediated pathways and immune modulation. Exciting novel immune therapy involving dendritic cell vaccines, B-cell vaccines and viral vectors may be the future of treating GBM.     

橡胶助剂现状与发展趋势

介绍世界和我国橡胶助剂行业现状。世界橡胶助剂市场供求基本平衡,利润下降,新开发产品减少,生产中心向亚洲转移。我国橡胶助剂发展很快,产品种类日益丰富,出口量显著增长,2012年销售额超过1亿元的橡胶助剂企业占比约70%。受上游市场低迷和贸易与技术壁垒影响,我国橡胶助剂行业机遇与挑战并存,重点发展的产品是环保和高性能橡胶助剂。