Excessive complement activation occurs in kidneys of patients with the new coronavirus (COVID-19)

A group from Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, etc. has reported excessive complement activation in kidneys of patients with the new coronavirus (COVID-19).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878379/

COVID-19 causes severe acute respiratory syndrome (ARDS), and the tissue damage is not restricted to lungs but also develop cardiac and kidney injury. In the case of kidneys, the glomerules and tubules seem to be damaged. Excessive activation of complements develops excessive membrane attack complex (MAC) resulting in damage of the glomerular and tubular tissues.
The table below shows a comparison of the level of complement expression among COVID-19 and typical kidney diseases comparing with a control.


ATI: acute tubular injury
HUS: hemolytic uremic syndrome
DIC: disseminated intravascular coagulation

The functions of glycans and lectins in myogenesis: Galectin-1 promotes muscle development

A group from University of Melbourne, etc. has investigated changes in glycan modification in myogenesis over time, while studying the functions of Galectins.
https://www.mcponline.org/article/S1535-9476(20)35144-6/fulltext

In myogenesis, there was a tendency that terminal di-Gal modification down regulated, α2-6Sia modification up regulated, α2-3Sia modification down regulated inversely, and paucimannose up regulated. These changes were thought to be related to intercellular signaling in myogenesis, but the specific signal paths were still unknown. On the other hand, as for galectins, the expression of Galectin-1 increased and the expression of Galectin-3 decreased.
Using newborn mice, an empty multiple cloning site (MCS) was injected with AAV6 into the left foot (as a control), and a galectin-1 gene (LGALS1) was injected with AAV6 into the right foot, and the difference between them was compared after 42 days. it was found that muscle mass was significantly increased with the injection of LGALS1. So, it is clear that galectin-1 is able to promote muscle development.
In the figure below, 14-3-3 protein was referenced as a comparison of LGALS1. 14-3-3 protein is related to intercellular signaling, and recognizes Ser/Thr residues in a specific domain of target protein with a phosphorylation-dependent way, and extracts the physiological function of the phosphorylation state.

Efficacy of therapeutic agents targeting Galectin-3 for breast and ovarian cancers

A group from Memorial Sloan Kettering Cancer Center, New York etc. has reported on the development of therapeutic agents targeting Galectin-3 for breast and ovarian cancers.
https://www.nature.com/articles/s41598-021-82686-3

In ovarian and breast cancers, mucin named MUC16 with CA125 epitope is highly expressed. Mucins are strongly glycosylated with O-glycans, and the glycan chains are sometimes stretched by adding a poly LacNAc chain to the terminal. Galectin-3 (Gal-3) has affinity to the poly LacNAc, hence Gal-3 could bind to MUC16 via such glycans. Galectin family has various functions, and MUC16 is closely related to cancer cells and is considered to be related to cancer growth and metastasis.

Using a monoclonal antibody (14D11) against Gal-3, the authors evaluated the inhibitory effects of Gal-3 on ovarian and breast cancers in vitro and in vivo. The Kd value for Gal-3 and LacNAc binding was ~0.2mM, and the Kd value for Gal-3 and 14D11 was ~14.6nM. Therefore, it turns out that 14D11 has stronger affinity about 13,000 times.

Two ovarian cancer cell lines (A2780, SKOV3) with high expression of MUC16 were transplanted into mice and the effects of 14D11 administration were compared with survival rates.

In addition, breast cancer cells (MDA-MB-231) were transplanted into mice and the effects of 14D11 administration were compared as below. These experimental results show that inhibition of Gal-3 can reduce cancer growth significantly.

ACE2-Fc fusion protein expressed in N. benthamiana as a therapeutic drug against the new coronavirus (SARS-CoV-2)

A group from UC Davis had proposed the idea of using ACE2-Fc fusion protein as a therapeutic agent for COVID-19 as follows,
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237295

A group from Chulalongkorn University, Bangkok, Thailand etc. has  developed ACE2-Fc fusion proteins expressed in N. benthamiana leaf, and demonstrated the inhibitory effect of SARS-CoV-2 in vitro. Vero cells were infected with SARS-CoV-2, and then ACE2-Fc fusion protein was applied, 0.84 μg/ml (IC50) was obtained as the inhibitory effect. Why did authors use plants? The advantages of using plants are low cost, scalability of production, and no risks from pathogens of animal or human origin.
https://www.frontiersin.org/articles/10.3389/fpls.2020.604663/full

Strain determination of influenza virus using glycan array formed on an Arrayed Imaging Reflectometry (AIR) platform

A group from Univ. of Rochester’s group has developed and used sensor chips with various glycans immobilized on the Arrayed Imaging Reflectometry (AIR) platform as a simple way to detect the hemagglutinin subtypes of influenza viruses and the subtypes of neuraminidase.
https://pubs.acs.org/doi/10.1021/acs.bioconjchem.0c00718

What is more curious is what is the Arrayed Imaging Reflectometry (AIR) platform rather than the application example itself. This platform seemed to be developed in Benjamin Miller Lab., Univ. of Rochester. The principle is physically very simple, growing a thin oxide on a Si substrate with the mirror surface, and using the interference effect of light reflected on the upper and lower surfaces of SiO2 (i.e., at the SiO2/Si interface). There could be a reflection condition that the surface becomes non-reflective as a result of the interference of the diagonally incident light onto the substrate, and molecular interaction between probes pre-fixed on the substrate and applied ligands happens, reflected light appears depending on degree of disruption of the light interference. Therefore, like SPR, AIR does not need fluorescence labeling to the sample (i.e., label-free). The question about this technology would be the sensitivity. However, the above example explained that it provides comparable or better sensitivity than SPR.
https://www.urmc.rochester.edu/labs/benjamin-miller/projects/arrayed-imaging-reflectometry.aspx

Prognostic markers for IgA nephropathy: Lectins detect changes in glycan modification

A group from Okayama University School of Medicine has reported on a study focusing on glycans and lectins as prognosis markers for IgA nephropathy.
https://www.nature.com/articles/s41598-020-77736-1

They have found excellent prognostic markers from urine as a diagnostic sample with using lectin microarrays for 157 IgA nephropathy patients who received a renal biopsy from 2010 to 2017 at Okayama University Hospital.
The prognosis outcome were based on a decrease in glomerular filter rate (eGFR) (> 4 mL/min/1.73 m2/year), or eGFR ≥ 30% decline from baseline. T Score was used for the statistical evaluation, and  it was found that ECA lectins (with glycan binding specificity to Galβ1-4GlcNAc) and NPA lectins (with glycan binding specificity to High Mannose) could be good prognostic markers.
ECA:(odds ratio[OR] 2.84, 95% confidence interval[CI] 1.11–7.28)
NPA:(OR 2.32, 95% CI 1.11–4.85)
T Score is calculated by multiplying the standardized percentile rank by 10 and adding 50. T0, T1, T2 indicate Oxford classification about tubular atrophy and interstitial fibrosis.

On the effects of O-glycan modification around furin cleavage site of the new coronavirus (SARS-CoV-2), the infectivity of UK variant (B.1.1.7)

A group of NIH has reported the effects of O-glycan modification around the furin cleavage site of the new coronavirus (SARS-CoV-2) to the increased infectivity of the UK variant (B.1.1.7).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872346/

At the S1/S2 boundary of SARS-CoV-2 S-protein, an unique sequence of 4 amino acids (PRRA) is inserted forming the furin cleavage site as shown below.

 

 

 

S673, T676 are the positions where O-glycans are modified, as shown above. The presence of proline at 681 was deeply related to O-glycan modification at those positions. The authors also found that GALNT1 is the most active one glycosylating the furin proximal region among glycosyltransferase GALNT family. Furthermore, addition of O-glycans was shown to significantly suppress the cleavage at the furin cleavage site into S1 and S2. The UK variant (B.1.1.7) has a mutation called P681H, which replaces proline with histidine. Based on the above mentioned results, it is inferred that the non-presence of proline at 681 in UK variant suppresses O-glycan modification, resulting in increased cleavage efficiency and increased infectability.

A regenerative medicine approach to thin endometrium (endometrial stunting) which is one of causes of infertility

A group from the Center for Child Health and Development described a regenerative medicine approach to thin endometrium (endometrial stunting), which is one of causes of infertility.
https://stemcellres.biomedcentral.com/articles/10.1186/s13287-021-02188-x

There are various causes of infertility, but one of them is a thin endometrium (endometrial stunting). It is known that thin endometrium make ovoimplantation difficult, but little is known about the reason. Treatments for endometrial stunting include (1)estradiol replacement, mineral and vitamin administration, and from regenerative medicine approaches, (2) administration of platelet-rich plasma, (3) menstruation-derived stem cells, and (4) use of autologous transplantation of exogenously prepared endometrium cell sheets.

In a regenerative medicine approach, however, it would be very important how efficiently to culture the endometrium under xeno-free conditions. The endometrium is basically difficult to culture with feeder-free, and from the view point of xeno-free, the authors have developed a method of using autologous endometrial stromal cells as a feeder  instead of MEF. They also used special media (ESTEM-HE) in terms of accelerating endometrial cell growth. In the figure below, continental medium is DMEM and epithelium-specific medium is a special medium named ESTEM-HE.

IgG of the new coronavirus (SARS-CoV-2) was found in bovine whey milked in November 2018 and August 2019

A group from Juntendo University etc. has found antibodies (IgG) against the S-protein of the new coronavirus (SARS-CoV-2) from bovine milk whey.

https://www.sciencedirect.com/science/article/pii/S0958694621000303?via%3Dihub

The bovine milk was prepared from New Zealand cows in November 2018 and August 2019, and they discovered the presence of IgG for RBD present in the S-protein of SARS-CoV-2 from the bovine milk whey. The genome sequence of the S-protein is shown below, and the epitope mapping of the IgG shows that RBD is the one. Therefore, IgG enriched from milk whey may show neutralize activity against SARS-CoV-2.
However, this bovine milk whey was milked before the spread of COVID-19, and it is difficult to think that the cows were infected with SARS-CoV-2, and it might have been infected with an unknown coronavirus that shares immunogenicity of SRAS-CoV-2.

 

 

Glycan modification changes in gastric epithelial cells infected with Helicobacter pylori

A group from Chinese Center for Disease Control and Prevention, Beijing etc. has infected gastric epithelial cells (GES-1) with Helicobacter pylori isolated from patients with different diseases, and investigated changes in glycan modification with lectin microarrays.
https://www.mdpi.com/2076-0817/10/2/168/htm

Patient’s disease states from which H. pylori bacteria were isolated were as follows:
Chronic gastritis (YN4-62),
Duodenal ulcer disease (M84, P164),
Gastric cancer (HLJ011, HLJ030),

The trend is characterized by the increase in α1-2Fuc and α2-3Sia modifications. GES-1 which was not infected with H. pylori, was used as a control, to compare changes in glycan expression levels. Red indicates increased ones.