Oral SARS-CoV-2 Inoculation Causes Nasal Viral Infection Leading to Olfactory Bulb Infection: An Experimental Study DOI Creative Commons
Rumi Ueha, Toshihiro Ito, Ryutaro Furukawa

и другие.

Frontiers in Cellular and Infection Microbiology, Год журнала: 2022, Номер 12

Опубликована: Июнь 13, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can cause long-lasting anosmia, but the impact of SARS-CoV-2 infection, which spread to nasal cavity via oral route, on olfactory receptor neuron (ORN) lineage and bulb (OB) remains undetermined. Using Syrian hamsters, we explored whether inoculation lead viral examined how affects ORN by site, investigated infection OB induce inflammation. On post-inoculation day 7, presence was confirmed in lateral area (OCAM-positive) not septum NQO1-positive OCAM-positive areas. The virus observed partially infiltrating epithelium, progenitor cells, immature ORNs, mature ORNs were fewer than controls. found nerve bundles OB, suggesting as a route for brain infection. We demonstrated that transoral from central nervous system possibility dysfunction due localized at site could damage all ORN-lineage cells.

Язык: Английский

A roadmap to pulmonary delivery strategies for the treatment of infectious lung diseases DOI Creative Commons

Siqin He,

Jiajia Gui,

Kun Xiong

и другие.

Journal of Nanobiotechnology, Год журнала: 2022, Номер 20(1)

Опубликована: Март 3, 2022

Abstract Pulmonary drug delivery is a highly attractive topic for the treatment of infectious lung diseases. Drug via pulmonary route offers unique advantages no first-pass effect and high bioavailability, which provides an important means to deliver therapeutics directly lesions. Starting from structural characteristics lungs biological barriers achieving efficient delivery, we aim review literatures in past decade regarding strategies used treat Hopefully, this article new insights into future development therapeutic against diseases point view. Graphical

Язык: Английский

Процитировано

119
Induced pluripotent stem cells (iPSCs): molecular mechanisms of induction and applications DOI Creative Commons

Jonas Cerneckis,

Hongxia Cai,

Yanhong Shi

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Апрель 26, 2024

The induced pluripotent stem cell (iPSC) technology has transformed in vitro research and holds great promise to advance regenerative medicine. iPSCs have the capacity for an almost unlimited expansion, are amenable genetic engineering, can be differentiated into most somatic types. been widely applied model human development diseases, perform drug screening, develop therapies. In this review, we outline key developments iPSC field highlight immense versatility of modeling therapeutic applications. We begin by discussing pivotal discoveries that revealed potential a nucleus reprogramming led successful generation iPSCs. consider molecular mechanisms dynamics as well numerous methods available induce pluripotency. Subsequently, discuss various iPSC-based cellular models, from mono-cultures single type complex three-dimensional organoids, how these models elucidate diseases. use examples neurological disorders, coronavirus disease 2019 (COVID-19), cancer diversity disease-specific phenotypes modeled using iPSC-derived cells. also used high-throughput screening toxicity studies. Finally, process developing autologous allogeneic therapies their alleviate

Язык: Английский

Процитировано

88
Microgliosis and neuronal proteinopathy in brain persist beyond viral clearance in SARS-CoV-2 hamster model DOI Creative Commons
Christopher Käufer,

Cara Sophie Schreiber,

Anna-Sophia Hartke

и другие.

EBioMedicine, Год журнала: 2022, Номер 79, С. 103999 - 103999

Опубликована: Апрель 16, 2022

Neurological symptoms such as cognitive decline and depression contribute substantially to post-COVID-19 syndrome, defined lasting several weeks after initial SARS-CoV-2 infection. The pathogenesis is still elusive, which hampers appropriate treatment. Neuroinflammatory responses neurodegenerative processes may occur in absence of overt neuroinvasion.Here we determined whether intranasal infection male female syrian golden hamsters results persistent brain pathology. Brains 3 (symptomatic) or 14 days (viral clearance) post versus mock (n = 10 each) were immunohistochemically analyzed for viral protein, neuroinflammatory response accumulation tau, hyperphosphorylated tau alpha-synuclein protein.Viral protein the nasal cavity led pronounced microglia activation olfactory bulb beyond clearance. Cortical but not hippocampal neurons accumulated alpha-synuclein, inflammation neurodegeneration. Importantly, all regions affected, line with selective vulnerability.Thus, despite virus brain, develop signatures proteinopathies that progressive neuronal dysfunction. Further depth analysis this important mechanism required.Federal Ministry Health (BMG; ZMV I 1-2520COR501), Federal Education Research (BMBF 01KI1723G), Science Culture Lower Saxony Germany (14 - 76103-184 CORONA-15/20), German Foundation (DFG; 398066876/GRK 2485/1), Luxemburgish National Fund (FNR, Project Reference: 15686728, EU SC1-PHE-CORONAVIRUS-2020 MANCO, no > 101003651).

Язык: Английский

Процитировано

77
SARS-CoV-2 VOC type and biological sex affect molnupiravir efficacy in severe COVID-19 dwarf hamster model DOI Creative Commons

Carolin M. Lieber,

Robert M. Cox, Julien Sourimant

и другие.

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Июль 29, 2022

Abstract SARS-CoV-2 variants of concern (VOC) have triggered infection waves. Oral antivirals such as molnupiravir promise to improve disease management, but efficacy against VOC delta was questioned and potency omicron is unknown. This study evaluates in human airway epithelium organoids, ferrets, a lethal Roborovski dwarf hamster model severe COVID-19-like lung injury. were equally inhibited by cells organoids. Treatment reduced shedding ferrets prevented transmission. Pathogenicity hamsters VOC-dependent highest for delta, gamma, omicron. All molnupiravir-treated survived, showing reduction virus load from one (delta) four (gamma) orders magnitude. effect size varied individual infected with significant males, not females. The recapitulates mixed trials alerts that benefit must be reassessed vivo evolve.

Язык: Английский

Процитировано

44
Lactoferrin: Antimicrobial impacts, genomic guardian, therapeutic uses and clinical significance for humans and animals DOI Creative Commons
Mohamed E. Abd El‐Hack, Sameh A. Abdelnour, Mahmoud Kamal

и другие.

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 164, С. 114967 - 114967

Опубликована: Июнь 6, 2023

Lactoferrin (LF) is a protein found in several bodily fluids, such as milk. This has diverse range of functions and evolutionarily conserved. multifunction with distinct biological abilities affecting mammals' immune structures. Reports indicated that the daily uptake LF from dairy products unsatisfactory detecting further health-promoting abilities. Research shown it protects against infection, mitigates cellular senescence, improves nutritional quality. Additionally, being studied potential treatment for various diseases conditions, including gastrointestinal issues infections. Studies have also demonstrated its effectiveness viruses bacteria. In this article, we'll look closer at structure activities, antimicrobial, anti-viral, anti-cancer, anti-osteoporotic, detoxifying, immunomodulatory properties. More specifically, protective effect oxidative DNA damage was clarified through ability to abolish damaging without interfacing host genetic material. Fortification mitochondria dysfunction syndromes via sustaining redox status biogenesis suppressing apoptosis autophagy singling. examine benefits lactoferrin provide an overview recent clinical trials conducted use laboratory living models.

Язык: Английский

Процитировано

26
Hamster organotypic modeling of SARS-CoV-2 lung and brainstem infection DOI Creative Commons
Marion Ferren, Valérie Favède, Didier Décimo

и другие.

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Окт. 4, 2021

SARS-CoV-2 has caused a global pandemic of COVID-19 since its emergence in December 2019. The infection causes severe acute respiratory syndrome and may also spread to central nervous system leading neurological sequelae. We have developed characterized two new organotypic cultures from hamster brainstem lung tissues that offer unique opportunity study the early steps viral screening antivirals. These models are not dedicated investigate how virus reaches brain. However, they allow validating tropism lungs demonstrating could infect cerebellum, mainly by targeting granular neurons. Viral induces specific interferon innate immune responses with patterns each organ, along cell death apoptosis, necroptosis, pyroptosis. Overall, our data illustrate potential rapid modeling complex tissue-level interactions during newly emerged virus.

Язык: Английский

Процитировано

56
SARS-CoV-2 Bearing a Mutation at the S1/S2 Cleavage Site Exhibits Attenuated Virulence and Confers Protective Immunity DOI Creative Commons
Michihito Sasaki, Shinsuke Toba, Yukari Itakura

и другие.

mBio, Год журнала: 2021, Номер 12(4)

Опубликована: Авг. 24, 2021

SARS-CoV-2 uses its spike protein to enter target cells. The is cleaved by a host protease, and this event facilitates viral entry broadens cell tropism.

Язык: Английский

Процитировано

44
Mucosal administration of a live attenuated recombinant COVID-19 vaccine protects nonhuman primates from SARS-CoV-2 DOI Creative Commons
Mariana F. Tioni, Robert Jordan,

Angie Silva Pena

и другие.

npj Vaccines, Год журнала: 2022, Номер 7(1)

Опубликована: Июль 29, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19 global pandemic. SARS-CoV-2 an enveloped RNA virus that relies on its trimeric surface glycoprotein spike for entry into host cells. Here we describe vaccine candidate MV-014-212, a live, attenuated, recombinant human syncytial expressing chimeric as only viral envelope protein. MV-014-212 was attenuated and immunogenic in African green monkeys (AGMs). One mucosal administration AGMs protected against challenge, reducing by more than 200-fold peak shedding nose. elicited immunoglobulin A nose neutralizing antibodies serum exhibited cross-neutralization variants concern Alpha, Beta, Delta. Intranasally delivered, live vaccines such entail low-cost manufacturing suitable deployment. currently Phase 1 clinical trials intranasal vaccine.

Язык: Английский

Процитировано

35
Eight-amino-acid sequence at the N-terminus of SARS-CoV-2 nsp1 is involved in stabilizing viral genome replication DOI

Shiori Ueno,

Sodbayasgalan Amarbayasgalan,

Yoshiro Sugiura

и другие.

Virology, Год журнала: 2024, Номер 595, С. 110068 - 110068

Опубликована: Апрель 8, 2024

Язык: Английский

Процитировано

7
Timing of exposure is critical in a highly sensitive model of SARS-CoV-2 transmission DOI Creative Commons
Ketaki Ganti, Lucas M. Ferreri, Chung-Young Lee

и другие.

PLoS Pathogens, Год журнала: 2022, Номер 18(3), С. e1010181 - e1010181

Опубликована: Март 25, 2022

Transmission efficiency is a critical factor determining the size of an outbreak infectious disease. Indeed, propensity SARS-CoV-2 to transmit among humans precipitated and continues sustain COVID-19 pandemic. Nevertheless, number new cases contacts highly variable underlying reasons for wide-ranging transmission outcomes remain unclear. Here, we evaluated viral spread in golden Syrian hamsters define impact temporal environmental conditions on through air. Our data show that exposure periods as brief one hour are sufficient support robust transmission. However, timing after infection success, with highest frequency occurring at times peak load donor animals. Relative humidity temperature had no detectable when exposures were carried out optimal high inoculation dose. contrary expectation, trends observed sub-optimal lower dose suggest improved relative or temperature. In sum, tested, our reveal be strongest determinant success implicate important driver

Язык: Английский

Процитировано

27