A novel biparatopic antibody-ACE2 fusion that blocks SARS-CoV-2 infection: implications for therapy

In the absence of a proven effective vaccine preventing infection by SARS-CoV-2, or a proven drug to treat COVID-19, the positive results of passive immune therapy using convalescent serum provides a strong lead. We have developed a new class of tetravalent, biparatopic therapy, 89C8-ACE2. It combines the specificity of a monoclonal antibody (89C8) that recognizes the relatively conserved N-terminal domain (NTD) of the viral S glycoprotein, and the ectodomain of ACE2, which binds to the receptor-binding domain (RBD) of S. This molecule shows exceptional performance in vitro, inhibiting the interaction of recombinant S1 to ACE2 and transduction of ACE2-overexpressing cells by S-pseudotyped lentivirus with IC50s substantially below 100 pM, and with potency approximately 100-fold greater than ACE2-Fc itself. Moreover, 89C8-ACE2 was able to neutralize authentic virus infection in a standard assay at low nanomolar concentrations, making this class of molecule a promising lead for therapeutic applications.

The combination of acyclovir and dexamethasone protects against Alzheimer's disease-related cognitive impairments in mice.

Alzheimer's disease (AD) is the most common neurodegenerative disease. However, effective drugs for this disease have not yet been developed. The analysis of big data indicated that childhood herpes virus infection may be associated with the incidence of AD, suggesting that anti-herpetic drugs, such as acyclovir, may have preventive and suppressive effects in AD therapy. Moreover, short-term use of dexamethasone (DXMT), a clinical used synthetic corticosteroid, could effectively inhibit AD-related neuroinflammation. In this study, we have found that the combination of acyclovir and DXMT, but not acyclovir or DXMT alone, could protect against AD causing ß-amyloid (Aß) oligomer-induced spatial cognitive impairments. Moreover, acyclovir and DXMT could prevent Aß oligomer-induced over-activation of microglia and astrocytes, and over-expression of pro-inflammatory cytokines, indicating that anti-AD effects of drug combination might be at least partially via neuroinflammation inhibition and immunomodulation. Furthermore, Aß oligomer-induced decrease of PSD-95 and increase of pTau expression was prevented by the combination of acyclovir and DXMT, suggesting the involvement of synaptic protective effects of the drug combination. Taken together, our studies indicated that the combination of acyclovir and DXMT might be an alternative therapy for the treatment of AD.

Effects of different anesthesia methods on cognitive function and inflammatory factors in elderly patients with lung cancer during perioperative period / 中国基层医药

Objective To explore the effects of different anesthesia methods on cognitive function and serum interleukin-6 ( IL -6), interleukin -8 ( IL -8) levels in elderly patients with lung cancer during perioperative period.Methods From March 2015 to March 2017, ninety elderly patients undergoing radical resection of lung cancer treated in Heji Hospital Affiliated to Changzhi Medical College were selected in the research.According to the different anesthesia methods,they were divided into inhalation anesthesia group( A group),general intravenous anes-thesia group(B group) and epidural block anesthesia group(C group),with 30 cases in each group.The minimum mental state examination(MMSE) scores,cognitive dysfunction rate,serum IL-6 and IL-8 levels of the three groups before operation,one day after operation and three days after operation were compared.Results One day and three days after operation,the MMSE scores of C group were (25.62 ± 2.11) points,(27.12 ± 2.04) points,respectively, which were higher than those of group A[(22.61 ± 2.75) points,(25.78 ± 2.68)points] and B group[(22.34 ± 2.01)points,(25.81 ± 2.42) points],the differences were statistically significant(tA group =4.756,2.179,tB group =6.165,2.267,all P<0.05).One day and three days after operation,the cognitive dysfunction rates of C group were 26.67% (8/30),6.67% (2/30),respectively,which were lower than those of A group[50.00% (15/30),26.67% (8/30)] and B group[66.67% (20/30),30.00% (9/30)],the differences were statistically significant(χ2A group =3.455,4.320,χ2B group =9.643,5.455,all P<0.05).One day and three days after operation,the serum IL-6 and IL-8 levels of C group[IL-6:(99.53 ± 16.82)ng/mL,(83.24 ± 8.34) ng/mL,IL-8:(50.43 ± 7.84)ng/mL, (42.15 ± 5.25)ng/mL] were lower than those of A group[IL-6:(122.43 ± 18.41)ng/mL,(88.51 ± 10.42)ng/mL, IL-8:(64.53 ± 8.94)ng/mL,(55.62 ± 6.78) ng/mL] and B group[IL-6:(124.52 ± 20.10) ng/mL,(87.95 ± 9.34)ng/mL,IL-8:(63.27 ± 9.03)ng/mL,(54.62 ± 6.30) ng/mL],the differences were statistically significant (IL-6:tA group =5.030,2.163,tB group =5.222,2.060,all P<0.05;IL-8:tA group =6.495,8.604,tB group =5.881, 8.329,all P<0.05).Conclusion The influence of epidural block anesthesia on postoperative cognitive dysfunction in elderly patients with radical resection of lung cancer is minimal,which can inhibit the expression of inflammatory factors.It is better than the other two anesthesia methods,and it is worthy of radical operation for elderly patients with lung cancer.

Stem cell therapy for ischemic stroke / 中国组织工程研究

BACKGROUND:Stem cells are a kind of cells characterized as species diversity, self-replication and renewal ability, multiple differentiation potential and high proliferation potential. Then, the stem celltreatment for ischemic brain injury would be of great benefit. Stem celltherapy provides a new way for the treatment of ischemic stroke, but the mechanism is stil unclear. OBJECTIVE:To describe the types of stem cells and review the mechanism underlying stem celltreatment for ischemic stroke. METHODS:The first author retrieved PubMed database, Chinese Journal Ful-text Database for articles related to stem cellclassification and effectiveness, safety and mechanism of stem celltherapy for ischemic stroke published from January 1992 to September 2012. The key words were“stem cells, brain ischemic stroke, transplantation, treatment”in English and Chinese, respectively. A total of 168 literatures were retrieved, and 61 articles met the inclusion criteria. RESULTS AND CONCLUSION:Stem celltherapy for ischemic stroke has shown a promising prospect though it is staged in the period of animal models. Stem celltransplantation for promoting functional recovery in the treatment of stroke has been completed in the clinical phase I or phase II trials. Stem celltransplantation for ischemic stroke appears to have no adverse reactions and to promote functional recovery. Main difficulties in stem celltransplantation for treatment of ischemic stroke include sources of stem cells, transplantation approach, stem cellsurvival in the host body, stem cellintegration with the host brain, therapeutic effectiveness and security. Based on the acquired results from the mechanism research and clinical trials, how to safely and quickly apply the stem celltherapy from the experiments to the clinic stil needs to work.