Archive 22/4/10

A group from Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands, etc. has reported that the binding specificity of hemagglutinin on influenza A virus can be switched from NeuAc to NeuGc by introducing several mutations.
https://pubmed.ncbi.nlm.nih.gov/35044215/

Influenza A viruses (IAV) initiate infection by binding to glycans with terminal sialic acids on the cell surface. Hosts of IAV variably express two major forms of sialic acid, N-acetylneuraminic acid (NeuAc) and N-glycolylneuraminic acid (NeuGc). NeuGc is present only in species that express an active form of the enzyme CMP-N-acetyl neuraminic acid hydroxylase (CMAH), which facilitates the hydroxylation of NeuAc to convert it to NeuGc. The gene encoding CMAH, mainly expressed in mammalian species, has been partially or completely lost at several distinct events during evolution, causing NeuGc to be absent in, among others, humans, ferrets, European dogs, and avian species.

NeuGc binding specificity on hemagglutinin was achevied by the following methods,
(1) combining mutation A135E with mutations I130V or T189A+K193R in A/Chicken/Jalisco/12283/2012 H7N3 HA,

(2) combining five mutations S128T, I130V, A135E, T189A, and K193R in A/Turkey/Italy/214845/02 H7N3 HA, and

(3) combining three mutations A135E, D189A, and K193R or five mutations S128T, I130V, A135E, D189A, and K193R in A/Duck/Australia/341/1983 H15N8 HA.

A group from Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China, etc. has reported that targeting TGF-β1 pathway might be a promising approach to enhance immune checkpoint blockade PD-1/PD-L1 in nasopharyngeal carcinoma (NPC).
https://pubmed.ncbi.nlm.nih.gov/35311117/

It is well known that PD-L1, programmed death ligand-1, is a transmembrane glycoprotein expressed by tumor cells and PD-L1 inhibits T cells activity and promotes immune evasion through binding to its receptor PD-1 on T cells.

TGF-β is a multifunctional cytokine with an important role in both physiologic and pathologic processes, including cancer. The aberrantly upregulated production of TGF-β has been strongly implicated in tumor progression, angiogenesis, and metastasis, as well as immune escape. TGF-β has been regarded as a critical immunosuppressive cytokine, which suppresses the antitumor activity of effector cells, including CD8⁺ T cells, natural killer (NK) cells, and macrophages.

In this study, it was confirmed that PD-L1 was heavily glycosylated in NPC, and found that TGF-β1 played an important role in N-glycosylation of PD-L1.
Inhibition of TGF-β1 by a TGF-β type I receptor inhibitor (SB431542) reduced not only PD-L1 expression but also PD-L1 glycosylation. The reduction of PD-L1 glycosylation was confirmed by loss of PD-L1 binding ability to ConA lectin.

Authors found that the glycosylation of PD-L1 was affected by TGF-β1 through c-Jun/STT3A signaling pathway, suggesting that targeting TGF-β1 pathway might be a promising approach to enhance immune checkpoint blockade in NPC avoiding deglycosylatin of PD-L1.

Co-culture of NPC cells (5-8F cells) and Jurkat T cells, conducted with STT3A-knockdown (shSTT3Acells), SB431542 and tunicamycin (TM) pretreatments on T cells.

A group from Department of Botany and Microbiology, Faculty of Science, Alexandria University, Alexandria 21511, Egypt, etc. has reported about alleviation of salinity stress in eggplants by using a biofertilizer.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8912713/

Chemical fertilizers have been widely used to achieve maximum crop productivity in conventional agricultural systems. Nevertheless, when chemical fertilizers exceed the threshold level, they accelerate soil acidification, pollute groundwater, and harm the environment overall. It is recommended to apply biofertilizers as eco-friendly alternatives as they play a pivotal role in phosphate solubilization, nitrogen fixation, production of ammonia, enzymes, siderophores, and secretion of variable phytohormones. Furthermore, they exhibit biocontrol activity against a wide variety of phytopathogenic agents.

In this study, the effect of selected bioinoculum (plant growth promoting rhizobcteria and rhizo fungi) on salinity stress in eggplants (Solanum melongena L.) was investigated as a biofertilizer.

Comparative experimental conditions were as follows:
(C): one irrigated with distilled water as a control,
(I): the second one inoculated with the selected inoculum and irrigated with distilled water,
(S): the third one irrigated with 200 mM NaCl, and
(S + I): the fourth one irrigated with 200 mM NaCl and inoculated with selected inoculum.
Two strains of rhizobacteria (Bacillus subtilis and Pseudomonas sp.) and three strains of rhizofungi (Trichoderma harzianum, Aspergillus terrus, and Penicillium citrinum) were used as the inoculum (as a biofertilizer).

Salinity stress significantly decreased leaf area, root fresh and dry weights, in addition to root water content by (59.14, 95.87, 96.30, and 95.66%, respectively) compared to control, but the inoculating the soil of salt-stressed eggplants showed a significant increase in leaf area (LA), total fresh weight (TFW), total dry weight (TDW), and total water content(TWC) as shown below.

The gene expression of photosystem II D2, glutathione reductase, and glutathione S transferase was upregulated in inoculated salt-stressed eggplants with respect to stressed ones, that of protease I and protease II (cell-wall degrading enzymes to suppress pathogen growth) was also upregulated in inoculated salt-stressed eggplants with respect to stressed ones, and that of lipase was downregulated conversely in inoculated salt-stressed eggplants with respect to stressed ones.
These changes suggest that defense mechanism related genes are upregulated in inoculated eggplants.