Chengdu Rongsheng Pharmaceutical Co., Ltd.

Although the COVID-19 pandemic is no longer considered an emergency, the ongoing spread of the virus poses a persistent threat to public health. COVID-19 poses a challenge to the system due to the risk of saturation and the associated economic burden. To assess changes in the anti-SARS-CoV-2 antibody profile, we analyzed nine batches of intravenous immunoglobulin (IVIG) prepared from plasma samples collected between November 2020 and June 2023. Antibody changes against SARS-CoV-2 spike, nucleocapsid, and membrane proteins, and neutralizing antibodies were measured. Antibody titers against wild-type SARS-CoV-2 and the three variants consistently increased. Furthermore, different IVIG batches demonstrated that antibody-dependent cellular cytotoxicity activity was correlated with anti-spike and neutralizing antibody titers. The anti-SARS-CoV-2 antibody titers fluctuated according to the progress of the pandemic and changes in COVID-19 vaccine coverage. Our research shows that immune cell-mediated virus elimination and the neutralizing effects of anti-SARS-CoV-2 antibodies underlie the therapeutic effects of IVIG.

Intravenous immunoglobulin (IVIg) is widely used to treat autoimmune diseases, yet its precise mechanisms of action in systemic lupus erythematosus remain incompletely understood. Here, we employed an integrated multi-modal approach combining single-cell RNA sequencing, quantitative proteomics, flow cytometry, immunofluorescence, enzyme-linked immunosorbent assay, and histopathological analysis to investigate IVIg-induced immune reprogramming in MRL/lpr lupus-prone mice. IVIg treatment markedly alleviated disease manifestations, including splenomegaly, proteinuria, renal injury, and systemic autoantibody production. Histological examination of the spleen and kidney showed decreased lymphoid hyperplasia, glomerular inflammation, and tissue damage in IVIg-treated mice. At the immune-cell level, IVIg was associated with alterations in T and B cell activation states, partial restoration of immune repertoire diversity, and shifts in dendritic cell populations. Collectively, our integrated analyses suggest that IVIg treatment is correlated with broad immunomodulatory changes in splenic immune composition in lupus-prone mice.

Anandamide (AEA) played potent neuroprotective activities via cannabinoid type 1 (CB1) and 2 (CB2) receptor. N-Linoleyltyrosine (NITyr), as an AEA analogue, was synthesized in our laboratory and evaluated the neuroprotective effects and mechanisms for the first time. NITyr was synthesized via substitution reaction. The neuroprotective effects of NITyr were evaluated in a gerbil model of transient cerebral ischemia. Each gerbil was subjected to open field test (OFT), Rotard rod test (RRT), Morris water maze (MWM) successively and executed after animal behaviors. Part of the brain was stained with hematoxylin and eosin (HE) and Nissl staining, and the rest for biochemical analysis. NITyr could not increase spontaneous locomotor activity and ameliorate the anxiety behavior in the OFT but could improve the motor coordination in the RRT and the spatial memory impairment in the MWM. Immunohistochemically, NITyr could attenuate the ischemia-induced neural loss in the hippocampus. The Enzyme-linked immunosorbent assay (ELISA) suggested that NITyr ameliorated the inflammation and oxidative stress. Consistently, NITyr could up-regulate the expressions of p-phosphadylinositol 3-kinase (PI3K) and p-Akt but not PI3K and Akt in the hippocampus. In addition to oxidative stress, CB2 receptor antagonist AM630 but not CB1 receptor antagonist AM251 could reverse the above phenomena. However, CB1 receptor antagonist AM251 could reverse oxidative stress. Accordingly, NITyr could up-regulate the expressions of CB2 but not CB1. NITyr could improve the motor coordination, learning and memory impairments, neural loss in the hippocampus and the inflammation of the mice via CB2 receptor involvement of PI3K/Akt signaling pathway.