Publications

The pathogenesis of severe coronavirus disease 2019 (COVID-19) remains poorly understood. While several studies suggest that immune dysregulation plays a central role, the key mediators of this process are yet to be defined. Here, we demonstrate that plasma from a high proportion (93%) of critically ill COVID-19 patients, but not healthy controls, contains broadly auto-reactive immunoglobulin M (IgM) and less frequently auto-reactive IgG or IgA. Importantly, these auto-IgMs preferentially recognize primary human lung cells in vitro, including pulmonary endothelial and epithelial cells.

• Link: https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(21)00164-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2666379121001646%3Fshowall%3Dtrue#%20

Sunitinib is widely used as a first‑line treatment for advanced renal cell carcinoma (RCC). However, a number of patients with RCC who receive sunitinib develop drug resistance; and the biological mechanisms involved in resistance to sunitinib remain unclear. It has previously been suggested that the protein glutaminyl‑peptide cyclotransferase (QPCT) is closely related to sunitinib resistance in RCC. Thus, in the present study, in order to further examine the molecular mechanisms responsible for sunitinib resistance in RCC, sunitinib‑non‑responsive and ‑responsive RCC tissue and plasma samples were collected and additional experiments were performed in order to elucidate the molecular mechanisms responsible for sunitinib resistance in RCC.

• Link: https://www.spandidos-publications.com/10.3892/ijo.2021.5228

HuProt PPI: Protein kinases and phosphatases regulate cellular processes by reversible phosphorylation and dephosphorylation events. CPPED1 is a recently identified serine/threonine protein phosphatase that dephosphorylates AKT1 of the PI3K-AKT signalling pathway. We previously showed that CPPED1 levels are down-regulated in the human placenta during spontaneous term birth. In this study, based on sequence comparisons, we propose that CPPED1 is a member of the class III phosphodiesterase (PDE) subfamily within the calcineurin-like metallophosphoesterase (MPE) superfamily rather than a member of the phosphoprotein phosphatase (PPP) or metal-dependent protein phosphatase (PPM) protein families.

• Link: https://onlinelibrary.wiley.com/doi/10.1111/jcmm.16607

Regulatory T cells play a key role in immune tolerance to self-antigens, thereby preventing autoimmune diseases. However, no drugs targeting Treg cells have been approved for clinical trials yet. Here, a chimeric peptide is generated by conjugation of the cytoplasmic domain of CTLA-4 (ctCTLA-4) with dNP2 for intracellular delivery, dNP2-ctCTLA-4, and evaluated Foxp3 expression during Th0, Th1, Treg, and Th17 differentiation dependent on TGF-β. The lysine motif of ctCTLA-4, not tyrosine motif, is required for Foxp3 expression for Treg induction and amelioration of experimental autoimmune encephalomyelitis (EAE).

• Link: https://onlinelibrary.wiley.com/doi/10.1002/advs.202004973

HuProt Small Molecule: Elevated inflammatory signaling has been shown to play an important role in diabetic kidney disease (DKD). We previously developed a new anti-inflammatory compound LG4. In the present study, we have tested the hypothesis that LG4 could prevent DKD by suppressing inflammation and identified the underlying mechanism. Although LG4 treatment had no effect on the body weight and blood glucose levels, it remarkably reversed the hyperglycemia-induced pathological changes and fibrosis in the kidneys of T1DM mice. Importantly, hyperglycemia-induced renal inflammation evidenced by NF-κB activation and TNFα and IL-6 overexpression was greatly ameliorated with LG4 treatment.

• Link: https://www.dovepress.com/an-indole-2-carboxamide-derivative-lg4-alleviates-diabetic-kidney-dise-peer-reviewed-fulltext-article-JIR

Substantial studies indicate that autoantibodies to tumor-associated antigens (TAAbs) arise in early stage of lung cancer (LC). However, since single TAAbs as non-invasive biomarkers reveal low diagnostic performances, a panel approach is needed to provide more clues for early detection of LC. In the present research, potential TAAbs were screened in 150 serum samples by focused protein array based on 154 proteins encoded by cancer driver genes. Indirect enzyme-linked immunosorbent assay (ELISA) was used to verify and validate TAAbs in two independent datasets with 1,054 participants (310 in verification cohort, 744 in validation cohort).

• Link: https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.658922/full

HuProt Small Molecule: With the development of precision therapy, pharmacological research pays more and more attention to seek and confirm the target of drugs in order to understand the mechanism of drug action and reduce side effects. Screening candidate proteins can be effectively used to predict potential drug targets and toxicity. Therefore, a high-throughput drug-binding protein screening method based on protein microarray which contains over 21,000 human proteins was introduced in this investigation.

• Link: https://www.sciencedirect.com/science/article/pii/S0014299921000492?via%3Dihub

HuProt Antibody Specificity: Monoclonal antibodies (mAbs) and mAb derivatives have become mainstay pharmaceutical modalites. A critical assessment is to ascertain the specificity of these molecules prior to human clinical trials. The primary technique for determining specificity has been the immunohistochemistry (IHC)-based “Tissue Cross-Reactivity” (TCR) assay, where the candidate molecule is applied to > 30 tissues to look for unexpected staining. In the last few years, however, non-IHC array-based platforms have emerged that allow for screening 75–80% of the human membrane proteome, indicating a viable alternative and/or addition to the IHC methods.

• Link: https://www.sciencedirect.com/science/article/abs/pii/S027323002100012X?via%3Dihub

HuProt PPI: The period circadian regulator 3 (PER3) has been reported to play a negative role in human immortalized bone marrow-derived Scp-1 cells (iBMSCs) and patient adipose-derived stromal cells (PASCs) or a negative/positive role in mice adipogenesis. However, human PER3 (hPER3) was identified as a positive regulator of human adipose tissue-derived stromal cells (hADSCs) adipogenesis in this study. Silencing or overexpression of hPER3 in hADSCs inhibited and promoted adipogenesis in vitro. In vivo, the overexpression of hPER3 increased high-fat diet-induced inguinal white adipose tissue (iWAT) and epididymal white adipose tissue (eWAT) forms, increasing systemic glucose intolerance and insulin resistance.

• Link: https://www.nature.com/articles/s41419-021-03584-0

Objective To discover systemic characteristics in the repertoires of targeted autoantigens in chronic inflammatory demyelinating polyneuropathy (CIDP), we detected the entire autoantigen repertoire of patients and controls and analyzed them systematically.

• Link: https://nn.neurology.org/content/8/2/e944