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rabindra.tharu.np@gmail.com
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Flortaucipir PET uncovers relationships between tau and amyloid-β in primary age-related tauopathy and Alzheimer’s disease
[F]-Flortaucipir positron emission tomography (PET) is considered a good biomarker of Alzheimer’s disease. However, it is unknown how flortaucipir is associated with the distribution of tau across brain regions and how these associations are influenced by amyloid-β. It is also unclear whether flortaucipir can detect tau in definite primary age-related tauopathy (PART). We identified 248…
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rabindra.tharu.np@gmail.com
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Extracellular vesicle-packaged PIAT from cancer-associated fibroblasts drives neural remodeling by mediating m5C modification in pancreatic cancer mouse models
Perineural invasion (PNI) is a biological characteristic commonly observed in pancreatic cancer. Although PNI plays a key role in pancreatic cancer metastasis, recurrence, and poor postoperative survival, its mechanism is largely unclarified. Clinical sample analysis and endoscopic ultrasonographic elasticity scoring indicated that cancer-associated fibroblasts (CAFs) were closely related to the occurrence of PNI. Furthermore, CAF-derived…
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rabindra.tharu.np@gmail.com
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Comparative single-cell analysis reveals IFN-γ as a driver of respiratory sequelae after acute COVID-19
Postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) represent an urgent public health challenge and are estimated to affect more than 60 million individuals globally. Although a growing body of evidence suggests that dysregulated immune reactions may be linked with PASC symptoms, most investigations have primarily centered around blood-based studies, with…
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rabindra.tharu.np@gmail.com
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Vasohibin inhibition improves myocardial relaxation in a rat model of heart failure with preserved ejection fraction
Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome associated with increased myocardial stiffness and cardiac filling abnormalities. Prior studies implicated increased α-tubulin detyrosination, which is catalyzed by the vasohibin enzymes, as a contributor to increased stabilization of the cardiomyocyte microtubule network (MTN) and stiffness in failing human hearts. We explored whether increased…
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rabindra.tharu.np@gmail.com
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Molecular dissection of cobra venom highlights heparinoids as an antidote for spitting cobra envenoming
Snakebites affect about 1.8 million people annually. The current standard of care involves antibody-based antivenoms, which can be difficult to access and are generally not effective against local tissue injury, the primary cause of morbidity. Here, we used a pooled whole-genome CRISPR knockout screen to define human genes that, when targeted, modify cell responses to…
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rabindra.tharu.np@gmail.com
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Targeted genome editing restores auditory function in adult mice with progressive hearing loss caused by a human microRNA mutation
Mutations in () cause autosomal dominant deafness-50 (DFNA50), a form of delayed-onset hearing loss. Genome editing has shown efficacy in hearing recovery through intervention in neonatal mice, yet editing in the adult inner ear is necessary for clinical applications, which has not been done. Here, we developed a genome editing therapy for the mutation 14C>A…
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rabindra.tharu.np@gmail.com
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Preclinical studies show that Co-STARs combine the advantages of chimeric antigen and T cell receptors for the treatment of tumors with low antigen densities
Two types of engineered T cells have been successfully used to treat patients with cancer, one with an antigen recognition domain derived from antibodies [chimeric antigen receptors (CARs)] and the other derived from T cell receptors (TCRs). CARs use high-affinity antigen-binding domains and costimulatory domains to induce T cell activation but can only react against…
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rabindra.tharu.np@gmail.com
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Harmine and exendin-4 combination therapy safely expands human β cell mass in vivo in a mouse xenograft system
Five hundred thirty-seven million people globally suffer from diabetes. Insulin-producing β cells are reduced in number in most people with diabetes, but most individuals still have some residual β cells. However, none of the many diabetes drugs in common use increases human β cell numbers. Recently, small molecules that inhibit dual tyrosine-regulated kinase 1A (DYRK1A)…
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rabindra.tharu.np@gmail.com
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An open-label, randomized controlled trial to assess a ketogenic diet in critically ill patients with sepsis
Patients with sepsis experience metabolic and immunologic dysfunction that may be amplified by standard carbohydrate-based nutrition. A ketogenic diet (KD) may offer an immunologically advantageous alternative, although clinical evidence is limited. We conducted a single-center, open-label, randomized controlled trial to assess whether a KD could induce stable ketosis in critically ill patients with sepsis. Secondary…
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rabindra.tharu.np@gmail.com
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Tissue-based T cell activation and viral RNA persist for up to 2 years after SARS-CoV-2 infection
The mechanisms of postacute medical conditions and unexplained symptoms after SARS-CoV-2 infection [Long Covid (LC)] are incompletely understood. There is growing evidence that viral persistence, immune dysregulation, and T cell dysfunction may play major roles. We performed whole-body positron emission tomography imaging in a well-characterized cohort of 24 participants at time points ranging from 27…
