Emerging Patent Landscape for Gene Therapy as a Potential Cure for COVID-19

There is still a lack of effective therapies for treating SARS-CoV-2-infected patients, as doubts remain whether antibodies provide sufficient immunity for COVID-19, and the safety of vaccines under development needs further study. The treatment of coronavirus from the perspective of RNA interference-based gene therapy offers a more direct approach to combating viral genes in addition to traditional drugs and vaccines and is likely to have a promising future. In this paper, an analysis of the emerging patent landscape was given on gene therapies for coronavirus under development, highlighting patent applications' basic status, geographical distribution, time-series analysis of new inventors, and ranking of patent applicants. Relevant patents were also reviewed and summarized to provide ideas for the control of the current COVID-19 pandemic

GelMA-based bioactive hydrogel scaffolds with multiple bone defect repair functions: therapeutic strategies and recent advances

Abstract Currently, the clinical treatment of critical bone defects attributed to various causes remains a great challenge, and repairing these defects with synthetic bone substitutes is the most common strategy. In general, tissue engineering materials that mimic the structural, mechanical and biological properties of natural bone have been extensively applied to fill bone defects and promote in situ bone regeneration. Hydrogels with extracellular matrix (ECM)-like properties are common tissue engineering materials, among which methacrylate-based gelatin (GelMA) hydrogels are widely used because of their tunable mechanical properties, excellent photocrosslinking capability and good biocompatibility. Owing to their lack of osteogenic activity, however, GelMA hydrogels are combined with other types of materials with osteogenic activities to improve the osteogenic capability of the current composites. There are three main aspects to consider when enhancing the bone regenerative performance of composite materials: osteoconductivity, vascularization and osteoinduction. Bioceramics, bioglass, biomimetic scaffolds, inorganic ions, bionic periosteum, growth factors and two-dimensional (2D) nanomaterials have been applied in various combinations to achieve enhanced osteogenic and bone regeneration activities. Three-dimensional (3D)-bioprinted scaffolds are a popular research topic in bone tissue engineering (BTE), and printed and customized scaffolds are suitable for restoring large irregular bone defects due to their shape and structural tunability, enhanced mechanical properties, and good biocompatibility. Herein, the recent progress in research on GelMA-based composite hydrogel scaffolds as multifunctional platforms for restoring critical bone defects in plastic or orthopedic clinics is systematically reviewed and summarized. These strategies pave the way for the design of biomimetic bone substitutes for effective bone reconstruction with good biosafety. Graphical Abstract This review provides novel insights into the development and current trends of research on GelMA-based hydrogels as effective bone tissue engineering (BTE) scaffolds for correcting bone defects, and these contents are summarized and emphasized from various perspectives (osteoconductivity, vascularization, osteoinduction and 3D-bioprinting). In addition, advantages and deficiencies of GelMA-based bone substitutes used for bone regeneration are put forward, and corresponding improvement measures are presented prior to their clinical application in near future (created with BioRender.com)

MiR-98 modulates macrophage polarization and suppresses the effects of tumor-associated macrophages on promoting invasion and epithelial–mesenchymal transition of hepatocellular carcinoma

Abstract Background Tumor-associated macrophages (TAMs) are generally recognized as a promoter of tumor progression. miR-98 has been shown to suppress the proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) of hepatocellular carcinoma (HCC) cells. Here, we aim to investigate the role of miR-98-mediated macrophage polarization in HCC progression. Methods Human blood monocytes were isolated from healthy male donors and incubated with culture medium collected from HepG2 cells for 7 days. The phenotype of the macrophages was detected. The protein expression was detected by Western blot. Levels of cytokines secreted in culture medium were measured using the specific enzyme-linked immunosorbent assay kits. To explore the role of miR-98 in HCC-conditioned TAMs, HCC cells HepG2 and SMMC7721 were cultured with conditioned medium from HCC-conditioned TAMs that had been transfected with miR-98 mimic/inhibitor. Cell proliferation, migration and invasion assays were performed. Results HCC-conditioned TAMs possessed M2-like phenotype, including increased protein expression of CD163 and TNF-αlow, IL-1βlow, TGF-βhigh and IL-10high phenotype. HCC-conditioned TAMs also promoted proliferation, migration, invasion and EMT of HepG2 and SMMC7721 cells. Furthermore, miR-98 modulated macrophage polarization from M2 to M1 in HCC-conditioned TAMs, as evidenced by the alteration of M1- or M2-related cytokines. Moreover, miR-98 mimic significantly suppressed the HCC-conditioned TAMs-mediated promotion of cell migration, invasion and EMT in HepG2 and SMMC7721 cells compared with negative control, whereas miR-98 inhibitor exerted reversed effects. Conclusions miR-98 may play a vital role in regulating macrophage polarization, thereby suppressing the TAMs-mediated promotion of invasion and EMT in HCC

CAR-based cell therapy: evaluation with bibliometrics and patent analysis

Chimeric antigen receptors-based cell therapies have shown impressive preclinical and clinical success and revolutionized biomedicine. However, the link between science and invention, the impact of international cooperation, and the influence and prestige of CARs research have not been explored. This study analyzed the landscape of peer-reviewed articles and patents related to CARs. A total of 5,681 publications were analyzed using bibliometrics and machine learning-based text mining to assess publication metrics, subject areas, and research hotspots. 5,010 Inpadoc families were also analyzed for patent filing trends, priority countries, and applicant and inventor rankings. The results show that CARs research has the following distinctive features: high research prestige among research community; strong global geographical bias in both academic output and patenting patterns; strong links between science and invention, but significant differences among countries; and an inverse relationship between country size and international collaboration rates

Table_1_Overview of global publications on machine learning in diabetic retinopathy from 2011 to 2021: Bibliometric analysis.docx

PurposeTo comprehensively analyze and discuss the publications on machine learning (ML) in diabetic retinopathy (DR) following a bibliometric approach.MethodsThe global publications on ML in DR from 2011 to 2021 were retrieved from the Web of Science Core Collection (WoSCC) database. We analyzed the publication and citation trend over time and identified highly-cited articles, prolific countries, institutions, journals and the most relevant research domains. VOSviewer and Wordcloud are used to visualize the mainstream research topics and evolution of subtopics in the form of co-occurrence maps of keywords.ResultsBy analyzing a total of 1147 relevant publications, this study found a rapid increase in the number of annual publications, with an average growth rate of 42.68%. India and China were the most productive countries. IEEE Access was the most productive journal in this field. In addition, some notable common points were found in the highly-cited articles. The keywords analysis showed that “diabetic retinopathy”, “classification”, and “fundus images” were the most frequent keywords for the entire period, as automatic diagnosis of DR was always the mainstream topic in the relevant field. The evolution of keywords highlighted some breakthroughs, including “deep learning” and “optical coherence tomography”, indicating the advance in technologies and changes in the research attention.ConclusionsAs new research topics have emerged and evolved, studies are becoming increasingly diverse and extensive. Multiple modalities of medical data, new ML techniques and constantly optimized algorithms are the future trends in this multidisciplinary field. </p

MOESM1 of MiR-98 modulates macrophage polarization and suppresses the effects of tumor-associated macrophages on promoting invasion and epithelial–mesenchymal transition of hepatocellular carcinoma

Additional file 1: Figure S1. The differentiation proportion of different types of macrophages. (A) Human monocytes were isolated from PBMCs by sorting with anti-CD14 magnetic beads. Macrophages were prepared from these monocytes by culture for 7 days in RPMI 1640 medium containing 10% FBS in the presence of 50 ng/ml M-CSF. Flow cytometry revealed that the purified cells were >95% CD14+ cells. (B) To obtain M0 cells, CD14+monocytes were treated with serum-free medium for 48 h. To polarize M1 macrophages, macrophages were stimulated overnight with 100 ng/ml LPS, and 100 ng/ml IFN-Îł. To polarize M2 macrophages, macrophages were stimulated with overnight with 20 ng/ml IL-4. The differentiation proportion of M0 (CD16/23-CD206-), M1 (CD16/23+) and M2 (CD206+) macrophages detected by flow cytometry was 87%, 89% and 96%, respectively

Peroxygenase-Catalysed Sulfoxidations in Non-Aqueous Media

Chiral sulfoxides are valuable building blocks in asymmetric synthesis. However, the biocatalytic synthesis of chiral sulfoxides is still challenged by low product titres. Herein, we report the use of peroxygenase as a catalyst for asymmetric sulfoxidation under non-aqueous conditions. Upon covalent immobilisation, the peroxygenase showed stability and activity under neat reaction conditions. A large variety of sulfides was converted into chiral sulfoxides in very high product concentration with moderate to satisfactory optical purity (e. g. 626 mM of (R)-methyl phenyl sulfoxide in approx. 89 % ee in 48 h). Further polishing of the ee value via cascading methionine reductase A (MsrA) gave&gt;99 % ee of the sulfoxide. The robustness of the enzymes and high product titer is superior to the state-of-the-art methodologies. Gram-scale synthesis has been demonstrated. Overall, we demonstrated a practical and facile catalytic method to synthesize chiral sulfoxides.BT/Biocatalysi

Mechanism through which retrocyclin targets flavivirus multiplication

Currently, there are no approved drugs for the treatment of flavivirus infection. Accordingly, we tested the inhibitory effects of the novel \u3b8-defensin retrocyclin-101 (RC-101) against flavivirus infection, and investigated the mechanism underlying the potential inhibitory effects. First, RC-101 robustly inhibited both Japanese encephalitis virus (JEV) and Zika virus (ZIKV) infections. RC-101 exerted inhibitory effects on the entry and replication stages. Results also indicated that the non-structural protein NS2B-NS3 serine protease might serve as a potential viral target. Further, RC-101 inhibited protease activity at the micromolar level. We also demonstrated that with respect to the glycoprotein E protein of flavivirus, the DE loop of domain III, which is the receptor-binding domain of the E protein, might serve as another viral target of RC-101. Moreover, a JEV DE mutant exhibited resistance to RC-101, which was associated with deceased binding affinity of RC-101 to DIII. These findings provide a basis for the development of RC-101 as a potential candidate for the treatment of flavivirus infection.ImportanceRetrocyclin is an artificially humanized circular \u3b8-defensin peptide, containing 18 residues previously reported to possess broad antimicrobial activity. In this study, we found that retrocyclin-101 inhibited flavivirus (ZIKV and JEV) infections. Retrocyclin-101 inhibited NS2B-NS3 serine protease activity, suggesting that the catalytic triad of the protease is the target. Moreover, retrocyclin-101 bound to the DE loop of the E protein of flavivirus, which prevented its entry