Tocilizumab (TCZ), a monoclonal antibody against interleukin-6 (IL-6), emerged as an alternative treatment for COVID-19 patients with a risk of cytokine storms recently.In the present study, we aimed to discuss the treatment response of TCZ therapy in COVID-19 infected patients. The demographic, treatment, laboratory parameters of C-reactive protein (CRP) and IL-6 before and after TCZ therapy and clinical outcome in the 15 COVID-19 patients were retrospectively assessed. Totally 15 patients with COVID-19 were included in this study. Two of them were moderately ill, six were seriously ill and seven were critically ill. The TCZ was used in combination with methylprednisolone in eight patients. Five patients received the TCZ administration twice or more. Although TCZ treatment ameliorated the increased CRP in all patients rapidly, for the four critically ill patients who received an only single dose of TCZ, three of them (No. 1, 2, and 3) still dead and the CRP level in the rest one patient (No. 7) failed to return to normal range with a clinical outcome of disease aggravation. Serum IL-6 level tended to further spiked firstly and then decreased after TCZ therapy in 10 patients. A persistent and dramatic increase of IL-6 was observed in these four patients who failed treatment. TCZ appears to be an effective treatment option in COVID-19 patients with a risk of cytokine storms. And for these critically ill patients with elevated IL-6, the repeated dose of the TCZ is recommended.

. Metformin was proposed to be a candidate for host-directed therapy for COVID-19. However, its efficacy remains to be validated. In this study, we compared the outcome of metformin users and nonusers in hospitalized COVID-19 patients with diabetes. Hospitalized diabetic patients with confirmed COVID-19 in the Tongji Hospital of Wuhan, China, from January 27, 2020 to March 24, 2020, were grouped into metformin and no-metformin groups according to the diabetic medications used. The demographics, characteristics, laboratory parameters, treatments, and clinical outcome in these patients were retrospectively assessed. A total of 283 patients (104 in the metformin and 179 in the no-metformin group) were included in this study. There were no significant differences between the two groups in gender, age, underlying diseases, clinical severity, and oxygen-support category at admission. The fasting blood glucose level of the metformin group was higher than that of the no-metformin group at admission and was under effective control in both groups after admission. Other laboratory parameters at admission and treatments after admission were not different between the two groups. The length of hospital stay did not differ between the two groups (21.0 days for metformin versus 19.5 days for no metformin, P = 0.74). However, in-hospital mortality was significantly lower in the metformin group (3/104 (2.9%) versus 22/179 (12.3%), P = 0.01). Antidiabetic treatment with metformin was associated with decreased mortality compared with diabetics not receiving metformin. This retrospective analysis suggests that metformin may offer benefits in patients with COVID-19 and that further study is indicated.

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Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

The plant auxin indole-3-acetic acid (IAA) plays critical roles in plant growth and development. There are two main strategies proposed for plant synthesis of IAA: the Trp-dependent (TD) and the Trp-independent (TI) pathways. Four TD pathways, namely the indole-3-acetamide pathway, the indole-3-pyruvic acid pathway, the tryptamine pathway and the indole-3-acetaldoxime pathway, have been postulated, identified and extensively studied. On the other hand, neither genes nor mutants involved in the TI pathway have been identified to date. Interestingly, some bacteria have auxin synthesis pathways that are similar to those in plants, indicating conserved biosynthetic mechanisms. Over the past few years, genetic, biochemical and molecular studies have greatly advanced our understanding of auxin biosynthesis. This review both summarizes recent advances in genetic and molecular knowledge and addresses the unsolved questions regarding auxin biosynthesis pathways in plants.

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Background Diabetic wounds are one of the most common and serious complications of diabetes mellitus, characterized by the dysfunction of wound-healing-related cells in quantity and quality. Our previous studies revealed that human amniotic epithelial cells (hAECs) could promote diabetic wound healing by paracrine action. Interestingly, numerous studies demonstrated that exosomes derived from stem cells are the critical paracrine vehicles for stem cell therapy. However, whether exosomes derived from hAECs (hAECs-Exos) mediate the effects of hAECs on diabetic wound healing remains unclear. This study aimed to investigate the biological effects of hAECs-Exos on diabetic wound healing and preliminarily elucidate the underlying mechanism. Methods hAECs-Exos were isolated by ultracentrifugation and identified by transmission electron microscopy, dynamic light scattering and flow cytometry. A series of in vitro functional analyses were performed to assess the regulatory effects of hAECs-Exos on human fibroblasts (HFBs) and human umbilical vein endothelial cells (HUVECs) in a high-glycemic microenvironment. High-throughput sequencing and bioinformatics analyses were conducted to speculate the related mechanisms of actions of hAECs-Exos on HFBs and HUVECs. Subsequently, the role of the candidate signaling pathway of hAECs-Exos in regulating the function of HUVECs and HFBs, as well as in diabetic wound healing, was assessed. Results hAECs-Exos presented a cup- or sphere-shaped morphology with a mean diameter of 105.89 ± 10.36 nm, were positive for CD63 and TSG101 and could be internalized by HFBs and HUVECs. After that, hAECs-Exos not only significantly promoted the proliferation and migration of HFBs, but also facilitated the angiogenic activity of HUVECs in vitro. High-throughput sequencing revealed enriched miRNAs of hAECs-Exos involved in wound healing. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses have shown that the target genes of the top 15 miRNAs were highly enriched in the PI3K-AKT pathway. Further functional studies demonstrated that the PI3K-AKT-mTOR pathway was necessary for the induced biological effects of hAECs-Exos on HFBs and HUVECs, as well as on wound healing, in diabetic mice. Conclusions Our findings demonstrated that hAECs-Exos represent a promising, novel strategy for diabetic wound healing by promoting angiogenesis and fibroblast function via activation of the PI3K-AKT-mTOR pathway.