scholarly journals SARS-CoV-2 Infects Hamster Testes

2021 ◽  
Vol 9 (6) ◽  
pp. 1318
Author(s):  
Rafael K. Campos ◽  
Vidyleison N. Camargos ◽  
Sasha R. Azar ◽  
Clint A. Haines ◽  
Eduardo J. Eyzaguirre ◽  
...  
Keyword(s):  
Virus Replication ◽  
Post Infection ◽  
Genital Tract ◽  
Respiratory Virus ◽  
Ex Vivo ◽  
Infection Model ◽  
Histopathological Changes ◽  
Testosterone Levels ◽  
Testicular Cells ◽  
Underlying Mechanisms

The COVID-19 pandemic continues to affect millions of people worldwide. Although SARS-CoV-2 is a respiratory virus, there is growing concern that the disease could cause damage and pathology outside the lungs, including in the genital tract. Studies suggest that SARS-CoV-2 infection can damage the testes and reduce testosterone levels, but the underlying mechanisms are unknown and evidence of virus replication in testicular cells is lacking. We infected golden Syrian hamsters intranasally, a model for mild human COVID-19, and detected viral RNA in testes samples without histopathological changes up to one month post-infection. Using an ex vivo infection model, we detected SARS-CoV-2 replication in hamster testicular cells. Taken together, our data raise the possibility that testes damage observed in severe cases of COVID-19 could be partly explained by direct SARS-CoV-2 infection of the testicular cells.

scholarly journals Rag2 Deficiency Enhances Susceptibility to Systemic Mouse Adenovirus Type 1 Infection

Intervirology ◽  
2021 ◽  
Author(s):  
Han-Kyul Lee ◽  
Sun-Min Seo ◽  
Jun-Young Kim ◽  
Han-Woong Kim ◽  
Eui-Suk Jeong ◽  
...  
Keyword(s):  
Post Infection ◽  
Inflammatory Cell ◽  
Systemic Infection ◽  
Adenovirus Type ◽  
Infection Model ◽  
Histopathological Changes ◽  
Viral Loads ◽  
Severe Inflammation ◽  
Cytokines And Chemokines

Introduction: Recombination-activating gene 1 (Rag1) and Rag2, which are essential in V(D)J recombination, play a crucial role in B and T cell maturation. Method: We investigated the effects of Rag2 deficiency in clustered regularly interspaced short palindromic repeats/Cas9-mediated FVB-Rag2 knockout (KO) and wild-type (WT) mice infected with mouse adenovirus type 1 (MAV-1) via the intranasal route. Results: MAV-1 infection caused more severe histopathological changes in FVB-Rag2 KO mice than in WT mice. FVB-Rag2 KO mice exhibited moderate to severe inflammation on day 4 and severe inflammation on day 8 post infection. In contrast, WT mice showed mild inflammation on day 4 and mild to severe inflammation on day 8 post infection, including interstitial pneumonia and inflammatory cell infiltration in the lungs and liver. Viral loads in the spleen and kidneys were significantly higher in FVB-Rag2 KO mice than in WT mice on day 8 post infection. Levels of cytokines and chemokines, including MIP-1α, IP-10, IFN-α, IFN-γ, and TNF-α, were upregulated in the spleens of FVB-Rag2 KO mice compared with those of WT mice. The upregulation of several cytokines occurred concurrently with the histopathological changes. MAV-1 infection induced more severe systemic infection in FVB-Rag2 KO mice than in WT mice. Conclusion: In mice, Rag2 deficiency induces inflammatory cell recruitment via the upregulation of cytokine and chemokine levels. The MAV-1 infection model can be utilized to assess the efficacy and safety of therapeutic agents for human adenoviral diseases.

scholarly journals Persistent Airway Hyperresponsiveness Following Recovery from Infection with Pneumonia Virus of Mice

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 728
Author(s):  
Ajinkya R. Limkar ◽  
Caroline M. Percopo ◽  
Jamie L. Redes ◽  
Kirk M. Druey ◽  
Helene F. Rosenberg
Keyword(s):  
Airway Hyperresponsiveness ◽  
Respiratory Virus ◽  
Infection Model ◽  
Post Inoculation ◽  
Virus Infections ◽  
Long Term Effects ◽  
Lung Dysfunction ◽  
Syncytial Virus ◽  
Underlying Mechanisms ◽  
Precision Cut Lung Slices

Respiratory virus infections can have long-term effects on lung function that persist even after the acute responses have resolved. Numerous studies have linked severe early childhood infection with respiratory syncytial virus (RSV) to the development of wheezing and asthma, although the underlying mechanisms connecting these observations remain unclear. Here, we examine airway hyperresponsiveness (AHR) that develops in wild-type mice after recovery from symptomatic but sublethal infection with the natural rodent pathogen, pneumonia virus of mice (PVM). We found that BALB/c mice respond to a limited inoculum of PVM with significant but reversible weight loss accompanied by virus replication, acute inflammation, and neutrophil recruitment to the airways. At day 21 post-inoculation, virus was no longer detected in the airways and the acute inflammatory response had largely resolved. However, and in contrast to most earlier studies using the PVM infection model, all mice survived the initial infection and all went on to develop serum anti-PVM IgG antibodies. Furthermore, using both invasive plethysmography and precision-cut lung slices, we found that these mice exhibited significant airway hyperresponsiveness at day 21 post-inoculation that persisted through day 45. Taken together, our findings extend an important and versatile respiratory virus infection model that can now be used to explore the role of virions and virion clearance as well as virus-induced inflammatory mediators and their signaling pathways in the development and persistence of post-viral AHR and lung dysfunction.

In Vitro, In Silico and Ex Vivo Studies of Dihydroartemisinin Derivatives as Antitubercular Agents

2019 ◽  
Vol 19 (8) ◽  
pp. 633-644 ◽  
Author(s):  
Komal Kalani ◽  
Sarfaraz Alam ◽  
Vinita Chaturvedi ◽  
Shyam Singh ◽  
Feroz Khan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
In Silico ◽  
Ex Vivo ◽  
Virulent Strain ◽  
Infection Model ◽  
Mouse Bone Marrow ◽  
Significant Activity ◽  
Macrophage Infection ◽  
In Silico Studies

Introduction: As a part of our drug discovery program for anti-tubercular agents, dihydroartemisinin (DHA-1) was screened against Mtb H37Rv, which showed moderate anti-tubercular activity (>25.0 µg/mL). These results prompted us to carry out the chemical transformation of DHA-1 into various derivatives and study their antitubercular potential. Materials and Methods: DHA-1 was semi-synthetically converted into four new acyl derivatives (DHA-1A – DHA-1D) and in-vitro evaluated for their anti-tubercular potential against Mycobacterium tuberculosis H37Rv virulent strain. The derivatives, DHA-1C (12-O-(4-nitro) benzoyl; MIC 12.5 µg/mL) and DHA-1D (12-O-chloro acetyl; MIC 3.12µg/mL) showed significant activity against the pathogen. Results: In silico studies of the most active derivative (DHA-1D) showed interaction with ARG448 inhibiting the mycobacterium enzymes. Additionally, it showed no cytotoxicity towards the Vero C1008 cells and Mouse bone marrow derived macrophages. Conclusion: DHA-1D killed 62% intracellular M. tuberculosis in Mouse bone marrow macrophage infection model. To the best of our knowledge, this is the first-ever report on the antitubercular potential of dihydroartemisinin and its derivatives. Since dihydroartemisinin is widely used as an antimalarial drug; these results may be of great help in anti-tubercular drug development from a very common, inexpensive, and non-toxic natural product.

scholarly journals Modulation of Intestinal Phosphate Transport in Young Goats Fed a Low Phosphorus Diet

2021 ◽  
Vol 22 (2) ◽  
pp. 866
Author(s):  
Joie L. Behrens ◽  
Nadine Schnepel ◽  
Kathrin Hansen ◽  
Karin Hustedt ◽  
Marion Burmester ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Phosphate Transport ◽  
Ussing Chambers ◽  
Intestinal Epithelia ◽  
Pi Transport ◽  
Low Phosphorus ◽  
Small Intestinal ◽  
Underlying Mechanisms ◽  
Growing Goats ◽  
1,25 Dihydroxy Vitamin D3

The intestinal absorption of phosphate (Pi) takes place transcellularly through the active NaPi-cotransporters type IIb (NaPiIIb) and III (PiT1 and PiT2) and paracellularly by diffusion through tight junction (TJ) proteins. The localisation along the intestines and the regulation of Pi absorption differ between species and are not fully understood. It is known that 1,25-dihydroxy-vitamin D3 (1,25-(OH)2D3) and phosphorus (P) depletion modulate intestinal Pi absorption in vertebrates in different ways. In addition to the apical uptake into the enterocytes, there are uncertainties regarding the basolateral excretion of Pi. Functional ex vivo experiments in Ussing chambers and molecular studies of small intestinal epithelia were carried out on P-deficient goats in order to elucidate the transepithelial Pi route in the intestine as well as the underlying mechanisms of its regulation and the proteins, which may be involved. The dietary P reduction had no effect on the duodenal and ileal Pi transport rate in growing goats. The ileal PiT1 and PiT2 mRNA expressions increased significantly, while the ileal PiT1 protein expression, the mid jejunal claudin-2 mRNA expression and the serum 1,25-(OH)2D3 levels were significantly reduced. These results advance the state of knowledge concerning the complex mechanisms of the Pi homeostasis in vertebrates.

Inhaled Particulate Matter Affects Immune Responsiveness of Human Lung Phagocytes to Mycobacteria

2021 ◽  
Author(s):  
Brandon Anton Paarwater ◽  
Jomien Mouton ◽  
Samantha L Sampson ◽  
Stephanus T Malherbe ◽  
Jane A Shaw ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Post Infection ◽  
Ex Vivo ◽  
Early Time ◽  
Immune Responsiveness ◽  
Phenotypic Profile ◽  
Host Protection ◽  
Tnf Α ◽  
Long Term Impact

The influence of smoke- or air pollution-derived cytoplasmic particulate matter (PM) can be detrimental and lead to failed lung immunity. We investigated mycobacterial uptake, intracellular replication, and soluble immune mediator responses of human bronchoalveolar lavage cells (BALC) loaded with/without PM, to infection with mycobacterial strains. We observed that only BALC containing PM display an ex vivo phenotypic profile dominated by spontaneous interleukin (IL) -10 production. PM loaded BALC retained the ability to phagocytose both Mycobacterium bovis Bacille Calmette Guérin (BCG) and Mycobacterium tuberculosis (M.tb) ΔleuDΔpanCD at equal efficacy as clear non-PM loaded BALC. However, immune responsiveness, such as the production of IL-6 (p=0.015) and tumor necrosis factor (TNF)-α (p= 0.0172) immediately post M.bovis BCG infection, were dramatically lower in black BALC loaded with PM versus clear non-PM loaded BALC. By 24 hour post infection, differential immune responses to M.bovis BCG between black versus clear BALC waned, and instead, production of IL-6 (p= 0.03) and IL-1α (p= 0.04 ) by black BALC were lower versus clear BALC following M.tb ΔleuDΔpanCD infection. Considering that TNFα and IL-6 are characterized as critical to host protection against mycobacteria, our findings suggest that BALC loaded with inhaled PM, display lower levels of anti-mycobacterial mediators, and that the response magnitude differs according to infective mycobacterial strain. Even though this did not translate into altered mycobacterial killing at early time points post infection, the long-term impact of such changes remains to be established.

scholarly journals Total flavonoids from Astragalus alleviate endothelial dysfunction by activating the Akt/eNOS pathway

2017 ◽  
Vol 46 (6) ◽  
pp. 2096-2103 ◽  
Author(s):  
Qian Liu ◽  
Ling Zhang ◽  
Qiyuan Shan ◽  
Yuxia Ding ◽  
Zhaocai Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Vascular Endothelial Cells ◽  
Ex Vivo ◽  
Umbilical Vein ◽  
Cell Counting ◽  
Total Flavonoids ◽  
Vascular Endothelial ◽  
Protective Effects ◽  
Hypoxic Conditions ◽  
Underlying Mechanisms

Objective To investigate the vasodilative and endothelial-protective effects and the underlying mechanisms of total flavonoids from Astragalus (TFA). Methods The vasodilative activities of TFA were measured with a myograph ex vivo using rat superior mesenteric arterial rings. The primary human umbilical vein endothelial cell (HUVEC) viabilities were assayed using the cell counting kit-8 after hypoxia or normoxia treatment with or without TFA. Akt, P-Akt, eNOS, P-eNOS, Erk, P-Erk, Bcl-2 and Bax expression were analyzed using western blotting. Results TFA showed concentration-dependent vasodilative effects on rat superior mesenteric arterial rings, but had no effects on normal or potassium chloride precontracted arterial rings. TFA did not affect HUVEC viabilities in normoxia, but dramatically promoted cell proliferation in the concentration range of 1 to 30 µg/mL under hypoxia. Moreover, TFA significantly increased the ratios of P-Akt/Akt and P-eNOS/eNOS in vascular endothelial cells under hypoxic conditions, but did not change the P-Erk/Erk or Bcl-2/Bax ratios. Conclusions TFA might exhibit vasorelaxant and endothelial-protective effects via the Akt/eNOS signaling pathway.

scholarly journals Lymphatic Vascular Structures: A New Aspect in Proliferative Diabetic Retinopathy

2018 ◽  
Vol 19 (12) ◽  
pp. 4034 ◽  
Author(s):  
Erika Gucciardo ◽  
Sirpa Loukovaara ◽  
Petri Salven ◽  
Kaisa Lehti
Keyword(s):  
Diabetic Retinopathy ◽  
Ex Vivo ◽  
Tissue Level ◽  
Clinical Samples ◽  
Related Factors ◽  
Disease Etiology ◽  
Working Age ◽  
Vascular Structures ◽  
Underlying Mechanisms ◽  
End Stage

Diabetic retinopathy (DR) is the most common diabetic microvascular complication and major cause of blindness in working-age adults. According to the level of microvascular degeneration and ischemic damage, DR is classified into non-proliferative DR (NPDR), and end-stage, proliferative DR (PDR). Despite advances in the disease etiology and pathogenesis, molecular understanding of end-stage PDR, characterized by ischemia- and inflammation-associated neovascularization and fibrosis, remains incomplete due to the limited availability of ideal clinical samples and experimental research models. Since a great portion of patients do not benefit from current treatments, improved therapies are essential. DR is known to be a complex and multifactorial disease featuring the interplay of microvascular, neurodegenerative, metabolic, genetic/epigenetic, immunological, and inflammation-related factors. Particularly, deeper knowledge on the mechanisms and pathophysiology of most advanced PDR is critical. Lymphatic-like vessel formation coupled with abnormal endothelial differentiation and progenitor cell involvement in the neovascularization associated with PDR are novel recent findings which hold potential for improved DR treatment. Understanding the underlying mechanisms of PDR pathogenesis is therefore crucial. To this goal, multidisciplinary approaches and new ex vivo models have been developed for a more comprehensive molecular, cellular and tissue-level understanding of the disease. This is the first step to gain the needed information on how PDR can be better evaluated, stratified, and treated.

Impact of long-term testosterone treatment on plasma levels of free TFPI and TF-induced thrombin generation ex vivo in elderly men with low testosterone levels

2009 ◽  
Vol 102 (11) ◽  
pp. 945-950 ◽  
Author(s):  
Ingvild Agledahl ◽  
Johan Svartberg ◽  
John-Bjarne Hansen ◽  
Ellen Brodin
Keyword(s):  
Tissue Factor ◽  
Plasma Levels ◽  
Thrombin Generation ◽  
Ex Vivo ◽  
Favorable Effect ◽  
Elderly Men ◽  
Testosterone Treatment ◽  
Testosterone Levels ◽  
Low Testosterone ◽  
One Year

SummaryMen have a higher incidence of cardiovascular disease (CVD) than women of similar age, and it has been suggested that testosterone may influence the development of CVD. Recently, we demonstrated that elderly men with low testosterone levels had lower plasma levels of free tissue factor pathway inhibitor (TFPI) Ag associated with shortened tissue factor (TF)-induced coagulation initiation in a population based case-control study. Our hypothesis was that one year of testosterone treatment to physiological levels in elderly men would increase the levels of free TFPI Ag in plasma and have a favorable effect on TF-induced coagulation. Twenty-six men with low testosterone levels (≤11.0 nM) were randomly assigned to treatment with intramuscular testosterone depot injections (testosterone undecanoate 1,000 mg) or placebo in a double-blinded study. Each participant received a total of five injections, at baseline, 6, 16, 28 and 40 weeks, and TF-induced thrombin generation ex vivo and plasma free TFPI Ag were measured after one year. At the end of the study total and free testosterone levels were significantly higher in the testosterone treated group (14.9 ± 4.5 nM vs. 8.1 ± 2.4 nM; p<0.001, and 363.3 ± 106.6 pM vs. 187.3 ± 63.2 pM; p<0.001, respectively). Testosterone treatment for one year did neither cause significant changes in TF-induced thrombin generation ex vivo nor changes in plasma levels of free TFPI Ag. In conclusion, normalising testosterone levels by testosterone treatment for 12 months in elderly men did not affect TF-induced coagulation or plasma TFPI levels. The potential antithrombotic role of testosterone therapy remains to be elucidated.

scholarly journals The Durability of Vaccine Efficacy against Ocular HSV-1 Infection Using ICP0 Mutants 0∆NLS and 0∆RING Is Lost over Time

Pathogens ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1470
Author(s):  
Daniel J. J. Carr ◽  
Amanda Berube ◽  
Edward Gershburg
Keyword(s):  
Virus Replication ◽  
Vaccine Efficacy ◽  
Post Infection ◽  
Corneal Opacity ◽  
Short Term ◽  
Visual Axis ◽  
Virus Shedding ◽  
Virus Challenge ◽  
Hsv 1

Vaccines to viral pathogens in experimental animal models are often deemed successful if immunization enhances resistance of the host to virus challenge as measured by cumulative survival, reduction in virus replication and spread and/or lessen or eliminate overt tissue pathology. Furthermore, the duration of the protective response against challenge is another important consideration that drives a vaccination regimen. In the current study, we assessed the durability of two related vaccines, 0∆NLS and 0∆RING, against ocular herpes simplex virus type 1 (HSV-1) challenge in mice thirty days (short-term) and one year (long-term) following the vaccine boost. The short-term vaccine efficacy study found the 0∆RING vaccine to be nearly equivalent to the 0∆NLS vaccine in comparison to vehicle-vaccinated mice in terms of controlling virus replication and preserving the visual axis. By comparison, the long-term assessment of the two vaccines found notable differences and less efficacy overall as noted below. Specifically, the results show that in comparison to vehicle-vaccinated mice, the 0∆NLS and 0∆RING vaccinated groups were more resistant in terms of survival and virus shedding following ocular challenge. Moreover, 0∆NLS vaccinated mice also possessed significantly less infectious virus in the peripheral and central nervous systems but not the cornea compared to mice vaccinated with vehicle or 0∆RING which had similar levels. However, all vaccinated groups showed similar levels of blood and lymphatic vessel genesis into the central cornea 30 days post infection. Likewise, corneal opacity was also similar among all groups of vaccinated mice following infection. Functionally, the blink response and visual acuity were 25–50% lower in vaccinated mice 30 days post infection compared to measurements taken prior to infection. The results demonstrate a dichotomy between resistance to infection and functional performance of the visual axis that collectively show an overall loss in vaccine efficacy long-term in comparison to short-term studies in a conventional prime-boost protocol.

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