New gene discovery may change cancer and autoimmune treatment!

Researchers have identified the #SDR42E1 gene as crucial for absorbing vitamin D from the gut and metabolizing it into the active hormone calcitriol, which is essential for bone health, immune function, and cellular processes.

They used CRISPR/Cas9 gene editing to disable SDR42E1 in HCT116 colorectal cancer cells, resulting in a dramatic 53% reduction in cancer cell viability while leaving healthy cells unharmed. 1/ The gene disruption triggered widespread molecular changes affecting over 4,600 downstream genes involved in sterol metabolism and cancer-related signaling pathways.

A specific mutation in #SDR42E1 on chromosome 16 has been linked to vitamin D deficiency, causing the protein to be cut short and rendered inactive. 2/

A promising new COVID-19 vaccine candidate developed by researchers at the Centenary Institute and the University of Sydney has shown strong potential to protect against both current and emerging coronavirus variants.

By targeting features shared by a range of coronaviruses, the vaccine is designed to offer broader and longer-lasting protection as the virus continues to evolve. 1/ The new study shows that the vaccine candidate, named #CoVEXS5, protected mice from multiple coronaviruses, including the highly immune-evasive omicron XBB.1.5 variant and SARS-CoV-1, a relative of SARS-CoV-2 that was responsible for the 2002–2004 SARS outbreak. 2/

A new Yale study has found a promising target for treating the brain fog that can follow COVID-19 and offers new insight into a hypothesis about the origin of Alzheimer's disease.

Researchers obtained viable postmortem human retinal tissue and generated human retinal organoids that contain electrophysiologically active neurons.

They demonstrated that SARS-CoV-2 induced amyloid-β extracellular protein aggregates in human retinal explants and retinal organoids. 1/ While the etiology of Alzheimer’s disease remains unknown, there is growing support for the amyloid-β antimicrobial hypothesis.

Amyloid-β, the main component of amyloid plaques in Alzheimer’s disease, has been shown to be generated in the presence of microbes.

Entrapment of microbes by aggregated amyloid-β may serve as an innate immune response to pathogenic infections. 2/

A new study reviewed skeletal muscle adaptations & post-exertional malaise in #LongCOVID. People with LongCOVID show reduced skeletal muscle oxidative capacity, smaller muscle fibers & increased glycolytic activity, all which may explain fatigue & post-exertional malaise. 1/ Muscle biopsies revealed structural and metabolic changes similar to deconditioning, but also showed unique inflammatory and mitochondrial signatures, suggesting Long COVID involves distinct muscle pathology beyond simple inactivity. 2/

A new study finds that fragments of viral proteins, including SARS-CoV-2 spike peptides, can bind and either inhibit or activate human formyl peptide receptors (FPR1, FPR2, FPR3) which influences innate immune responses like neutrophil migration and NETosis. 1/ Formyl peptide receptors (FPRs) are pattern recognition receptors well-known for bacterial pathogen sensing. Researchers identified activator and inhibitor motifs for FPRs that are present on surface proteins of various viral pathogens. Peptides containing these motifs interact with all FPR family members and modulate various important immune functions in innate immune cells. 2/

Researchers used 3 RNA-seq datasets of 142 samples from Australia, the US and Russia to look at gene expression signatures in acute COVID infection and in #LongCOVID. They found that TNF-α/NF-κB pathway signatures could identify patients at risk of severe disease progression from acute COVID infection 1/ They also noted that OXPHOS and Myc pathway-associated signatures reflecting metabolic changes may be used as a biomarker for #LongCOVID diagnosis and severity stratification. 2/

Fibrinoloid (amyloid-containing) microclots are resistant to degradation and are found in a variety of diseases including #LongCOVID, ME/CFS, and sepsis. A NEW review looks at the use of laser speckle imaging (LSI) and laser Doppler imaging (LDI) to assess how fibrinaloid microclots can disrupt the microcirculation. 1/ The microcirculation typically refers to those capillaries less than 100 mm in diameter. Having shown that blood can clot into an anomalous amyloid form that is rather resistant to fibrinolysis, researchers have previously developed the idea that endothelial dysfunction can both lead to and be caused by the fibrinaloid microclots so formed, such that this can slow or block entirely parts of the microcirculation. 2/

A NEW study finds that infection with SARS-CoV-2 during the first year of the pandemic was associated with three to five times higher odds of cognitive impairment 2 years after infection. 1/ Survivors of the disease may require special attention from clinical doctors to diagnose and treat cognitive impairment, namely, those who were hospitalized for more than 15 days, in intermediate or intensive care units, and presented disorientation, changes in vision, gait or balance, during infection. 2/

A NEW study finds that anti-SARS-CoV-2 antibodies play a protective role against vital organ-related #LongCovid (LC) symptoms, especially cardiovascular symptoms, but are insufficient in preventing or limiting other highly prevalent LC symptoms, such as neurological, psychiatric and pulmonary. 1/ These data underscore the complexity of the potential involvement of anti-SARS-CoV-2 immune responses in either protecting against or contributing to the development of different #LongCovid phenotypes. 2/

A meta-analysis from Egypt of 125 studies involving over 4 million COVID survivors shows that months to years after infection, fatigue was the most common symptom at 43%. Around 27% of people experience cognitive impairment after COVID infection. 1/ Further, 28% experienced memory issues, 24% sleep disorders, 20% headaches, 16% dizziness, 14% depression, and 13% anxiety, with significant variability depending on follow‑up time, disease severity, sex, and BMI. 2/

A new review on neuroimmune pathophysiology of #LongCOVID explores how SARS-CoV-2 can cause lasting neurological symptoms through a combination of direct infection, immune dysregulation, and persistent inflammation. 1/ Key mechanisms include viral antigen persistence, autoimmunity, blood–brain barrier disruption, neurotransmitter imbalances, and glial cell dysfunction. The authors link these processes to cognitive impairment, fatigue, dysautonomia, and other Long COVID symptoms. 2/

I think, therefore I age!

As people get older, a growing population of cells starts to consume more energy — perhaps because the cells accumulate damage that leads them to rev up processes such as inflammation. 1/ An emerging hypothesis suggests that the brain accommodates these energy-hogging ‘senescent cells’ by stripping resources from other biological processes, which ultimately results in outward signs of ageing, such as greying hair or a reduction in muscle mass. 2/

A NEW study found that the SARS-CoV-2 nonstructural protein 15 (nsp15) helps the virus hide from the immune system in human lung and nasal cells. The nsp15 endoribonuclease is important in promoting virus replication and influencing disease severity. 1/ SARS2 variants lacking this activity exhibit impaired replication & cause milder disease, highlighting nsp15 as a key virulence factor. This underscores the importance of nsp15’s endoribonuclease activity in both promoting virus replication & influencing disease severity. 2/

Researchers developed a 23-amino acid peptide that mimics ACE2 and effectively binds the SARS-CoV-2 spike protein, preventing viral entry. 1/ The peptide demonstrated potent antiviral activity against both the original and Omicron strains, with a therapeutic index greater than 20, indicating strong potential for therapeutic use. 2/

A NEW preprint found that submaximal exercise in people with #LongCOVID caused large microclots to fragment into smaller microclots and this then triggered increases in inflammatory and vascular injury markers. 1/ The breakdown of large microclots, rather than clearing them from circulation, was linked to reduced oxygen uptake and heightened inflammation. 2/

Globally, NB.1.8.1 is now the dominant variant. The WHO has issued a warning about rising COVID-19 activity in the Western Pacific, Southeast Asia, and Eastern Mediterranean, driven by NB.1.8.1 this week.

H/T: @RajlabN Classified as a "variant under monitoring" by the WHO & “ Nimbus” by @TRyanGregory, NB.1.8.1 has triggered a seventh consecutive week of surges in Southeast Asia. Taiwan has seen ER visits double again this week. 2/

focustaiwan.tw/society/202505…

The relationship between the gut and #LongCOVID:

Researchers found that people with LongCOVID fatigue have damaged gut barriers & signs of immune activation.

Preexisting gastrointestinal symptoms before COVID infection predisposed people to developing LongCOVID fatigue. 1/ LongCOVID patients were found to have an increased LBP/sCD14 ratio & lower IL-33 levels, which indicates altered immune activation & a reduced intestinal barrier. In addition, there were increased IL-6 levels, which are considered a marker for systemic inflammation. 2/

A new study from Germany found that intravenous administration of the SARS-CoV-2 spike protein in mice led to neuroinflammation and accumulation of alpha-synuclein in brain regions associated with Parkinson’s disease. 1/ Authors also discovered “sex-dependent alterations in astrocyte reactivity and parvalbumin-positive interneurons.” 2/

A significant discovery in the fight against #LongCovid!

➡️ Researchers have identified the epipharynx, a part of the pharynx, as a key site for chronic inflammation driven by residual SARS-CoV-2 RNA. 1/ Using a next-generation molecular mapping technology called Visium HD spatial transcriptomics, researchers from Japan provided the world's first high-resolution spatial gene expression analysis of the epipharynx in patients with longCOVID. 2/

A new article on #LongCOVID shows that millions of Americans continue to suffer from LongCOVID which is a very complex and heterogeneous disease, with no diagnostic tests and no approved treatments. 1/ New clinical trials will target specific biological pathways including immune dysfunction and autoimmunity, viral persistence, and microclots rather than treating LongCOVID as a single disease. 2/

A study new finds that neutrophils—the most abundant white blood cells in humans—may be altered by SARS-CoV-2 virus to cease their normal function of destroying pathogens in the body and, instead, significantly inhibit other immune cells critical for fighting the virus. 1/ The study finds that in some COVID infections, SARS-CoV-2 may dramatically impair the immune response by reprogramming neutrophils—front-line immune cells central to fighting infections—into a cell type called polymorphonuclear myeloid derived suppressor cells (PMN-MDSCs) 2/