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  1. Article ; Online: A hypothesized role for dysregulated bradykinin signaling in COVID-19 respiratory complications.

    Roche, Joseph A / Roche, Renuka

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology

    2020  Volume 34, Issue 6, Page(s) 7265–7269

    Abstract: As of April 20, 2020, over time, the COVID-19 pandemic has resulted in 157 970 deaths out of 2 319 066 confirmed cases, at a Case Fatality Rate of ~6.8%. With the pandemic rapidly spreading, and health delivery systems being overwhelmed, it is imperative ...

    Abstract As of April 20, 2020, over time, the COVID-19 pandemic has resulted in 157 970 deaths out of 2 319 066 confirmed cases, at a Case Fatality Rate of ~6.8%. With the pandemic rapidly spreading, and health delivery systems being overwhelmed, it is imperative that safe and effective pharmacotherapeutic strategies are rapidly explored to improve survival. In this paper, we use established and emerging evidence to propose a testable hypothesis that, a vicious positive feedback loop of des-Arg(9)-bradykinin- and bradykinin-mediated inflammation → injury → inflammation, likely precipitates life threatening respiratory complications in COVID-19. Through our hypothesis, we make the prediction that the FDA-approved molecule, icatibant, might be able to interrupt this feedback loop and, thereby, improve the clinical outcomes. This hypothesis could lead to basic, translational, and clinical studies aimed at reducing COVID-19 morbidity and mortality.
    MeSH term(s) Betacoronavirus ; Bradykinin/analogs & derivatives ; Bradykinin/pharmacology ; Bradykinin/physiology ; Bradykinin/therapeutic use ; Bradykinin B2 Receptor Antagonists/pharmacology ; Bradykinin B2 Receptor Antagonists/therapeutic use ; Compassionate Use Trials ; Coronavirus Infections/complications ; Coronavirus Infections/drug therapy ; Coronavirus Infections/physiopathology ; Dyspnea/etiology ; Dyspnea/physiopathology ; Feedback, Physiological/drug effects ; Humans ; Inflammation ; Models, Biological ; Off-Label Use ; Pandemics ; Peptidyl-Dipeptidase A/physiology ; Pneumonia, Viral/complications ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/physiopathology ; Receptors, Bradykinin/drug effects ; Receptors, Bradykinin/physiology ; Receptors, Virus/physiology
    Chemical Substances Bradykinin B2 Receptor Antagonists ; Receptors, Bradykinin ; Receptors, Virus ; bradykinin, des-Arg(9)- (15958-92-6) ; icatibant (7PG89G35Q7) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; angiotensin converting enzyme 2 (EC 3.4.17.-) ; Bradykinin (S8TIM42R2W)
    Keywords covid19
    Language English
    Publishing date 2020-05-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639186-2
    ISSN 1530-6860 ; 0892-6638
    ISSN (online) 1530-6860
    ISSN 0892-6638
    DOI 10.1096/fj.202000967
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Protection against Severe Illness versus Immunity-Redefining Vaccine Effectiveness in the Aftermath of COVID-19.

    Roche, Renuka / Odeh, Nouha H / Andar, Abhay U / Tulapurkar, Mohan E / Roche, Joseph A

    Microorganisms

    2023  Volume 11, Issue 8

    Abstract: Anti-SARS-CoV-2 vaccines have played a pivotal role in reducing the risk of developing severe illness from COVID-19, thus helping end the COVID-19 global public health emergency after more than three years. Intriguingly, as SARS-CoV-2 variants emerged, ... ...

    Abstract Anti-SARS-CoV-2 vaccines have played a pivotal role in reducing the risk of developing severe illness from COVID-19, thus helping end the COVID-19 global public health emergency after more than three years. Intriguingly, as SARS-CoV-2 variants emerged, individuals who were fully vaccinated did get infected in high numbers, and viral loads in vaccinated individuals were as high as those in the unvaccinated. However, even with high viral loads, vaccinated individuals were significantly less likely to develop severe illness; this begs the question as to whether the main effect of anti-SARS-CoV-2 vaccines is to confer protection against severe illness or immunity against infection. The answer to this question is consequential, not only to the understanding of how anti-SARS-CoV-2 vaccines work, but also to public health efforts against existing and novel pathogens. In this review, we argue that immune system sensitization-desensitization rather than sterilizing immunity may explain vaccine-mediated protection against severe COVID-19 illness even when the SARS-CoV-2 viral load is high. Through the lessons learned from COVID-19, we make the case that in the disease's aftermath, public health agencies must revisit healthcare policies, including redefining the term "vaccine effectiveness."
    Language English
    Publishing date 2023-07-31
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2720891-6
    ISSN 2076-2607
    ISSN 2076-2607
    DOI 10.3390/microorganisms11081963
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: A hypothesized role for dysregulated bradykinin signaling in COVID-19 respiratory complications

    Roche, Joseph A / Roche, Renuka

    FASEB J

    Abstract: As of April 20, 2020, over time, the COVID-19 pandemic has resulted in 157 970 deaths out of 2 319 066 confirmed cases, at a Case Fatality Rate of ~6.8%. With the pandemic rapidly spreading, and health delivery systems being overwhelmed, it is imperative ...

    Abstract As of April 20, 2020, over time, the COVID-19 pandemic has resulted in 157 970 deaths out of 2 319 066 confirmed cases, at a Case Fatality Rate of ~6.8%. With the pandemic rapidly spreading, and health delivery systems being overwhelmed, it is imperative that safe and effective pharmacotherapeutic strategies are rapidly explored to improve survival. In this paper, we use established and emerging evidence to propose a testable hypothesis that, a vicious positive feedback loop of des-Arg(9)-bradykinin- and bradykinin-mediated inflammation → injury → inflammation, likely precipitates life threatening respiratory complications in COVID-19. Through our hypothesis, we make the prediction that the FDA-approved molecule, icatibant, might be able to interrupt this feedback loop and, thereby, improve the clinical outcomes. This hypothesis could lead to basic, translational, and clinical studies aimed at reducing COVID-19 morbidity and mortality.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #155381
    Database COVID19

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  4. Article ; Online: A hypothesized role for dysregulated bradykinin signaling in COVID‐19 respiratory complications

    Roche, Joseph A. / Roche, Renuka

    The FASEB Journal

    2020  Volume 34, Issue 6, Page(s) 7265–7269

    Keywords Biotechnology ; Genetics ; Biochemistry ; Molecular Biology ; covid19
    Language English
    Publisher Wiley
    Publishing country us
    Document type Article ; Online
    ZDB-ID 639186-2
    ISSN 1530-6860 ; 0892-6638
    ISSN (online) 1530-6860
    ISSN 0892-6638
    DOI 10.1096/fj.202000967
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Damaged muscle fibers might masquerade as hybrid fibers - a cautionary note on immunophenotyping mouse muscle with mouse monoclonal antibodies.

    Begam, Morium / Roche, Joseph A

    European journal of histochemistry : EJH

    2018  Volume 62, Issue 3

    Abstract: We report that, labeling mouse muscle tissue, with mouse monoclonal antibodies specific to slow or fast myosin heavy chain (sMyHC and fMyHC, respectively), can lead to artefactual labeling of damaged muscle fibers, as hybrid fibers (sMyHC+ and fMyHC+). ... ...

    Abstract We report that, labeling mouse muscle tissue, with mouse monoclonal antibodies specific to slow or fast myosin heavy chain (sMyHC and fMyHC, respectively), can lead to artefactual labeling of damaged muscle fibers, as hybrid fibers (sMyHC+ and fMyHC+).  We demonstrate that such erroneous immunophenotyping of muscle may be avoided, by performing colabeling or serial-section-labeling, to identify damaged fibers. The quadriceps femoris muscle group (QF) in 7-month-old, male, C57BL/6J mice had: 1.21 ± 0.21%, 98.34 ± 1.06%, 0.07 ± 0.01%, and 0.53 ± 0.85% fibers, that were, sMyHC+, fMyHC+, hybrid, and damaged, respectively.  All fibers in the tibialis anterior muscle (TA) of 3-month-old, male, C57BL/6J mice were fMyHC+; and at 3 days after injurious eccentric contractions, there was no fiber-type shift, but ~ 18% fibers were damaged.
    MeSH term(s) Affinity Labels ; Animals ; Antibodies, Monoclonal/chemistry ; Immunophenotyping ; Mice ; Mice, Inbred C57BL ; Muscle, Skeletal ; Myosin Heavy Chains/chemistry
    Chemical Substances Affinity Labels ; Antibodies, Monoclonal ; Myosin Heavy Chains (EC 3.6.4.1)
    Language English
    Publishing date 2018-07-24
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 1109511-8
    ISSN 2038-8306 ; 0391-7258 ; 1121-4201 ; 1121-760X
    ISSN (online) 2038-8306
    ISSN 0391-7258 ; 1121-4201 ; 1121-760X
    DOI 10.4081/ejh.2018.2896
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Conference Report: 6th Annual International Symposium on Regenerative Rehabilitation.

    Loghmani, M Terry / Roche, Joseph A

    Regenerative medicine

    2018  Volume 13, Issue 4, Page(s) 371–374

    Abstract: The 6th International Symposium on Regenerative Rehabilitation, hosted by the Alliance for Regenerative Rehabilitation Research and Training ( ... ...

    Abstract The 6th International Symposium on Regenerative Rehabilitation, hosted by the Alliance for Regenerative Rehabilitation Research and Training (AR
    MeSH term(s) Animals ; Congresses as Topic ; Humans ; Occupational Therapy/methods ; Occupational Therapy/trends ; Physical Therapy Modalities/trends ; Regenerative Medicine/methods ; Regenerative Medicine/trends
    Language English
    Publishing date 2018-04-03
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2274500-2
    ISSN 1746-076X ; 1746-0751
    ISSN (online) 1746-076X
    ISSN 1746-0751
    DOI 10.2217/rme-2018-0026
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Extruded alginate tubes with myogenic potential.

    Lenneman, Cameron M / Rose, Emily M / Strawska, Brooke A / Tyszkiewicz, Natalie A / Dean-Christie, Karen / Katz, Erin / Roche, Joseph M / de Morree, Antoine / Roche, Renuka / Tulapurkar, Mohan E / Roche, Joseph A

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Background: There are currently no proven methods to reverse muscle loss in humans, which is caused by trauma (e.g., volumetric muscle loss, VML), genetic neuromuscular diseases (e.g., muscular dystrophies, MDs), and accelerated senescence (e.g., ... ...

    Abstract Background: There are currently no proven methods to reverse muscle loss in humans, which is caused by trauma (e.g., volumetric muscle loss, VML), genetic neuromuscular diseases (e.g., muscular dystrophies, MDs), and accelerated senescence (e.g., sarcopenia). Since muscle tissue is capable of regeneration through muscle satellite cells (MuSCs), the implantation of autologous (or other) donor MuSCs and MuSC-derived myoblasts into host muscles can promote donor-cell-derived myogenesis. Direct injection or implantation of MuSCs or MuSC-derived myoblasts into host muscles only promotes minimal donor-cell-derived myogenesis, whereas implantation of MuSCs/myoblasts along with associated muscle tissue (muscle fibers, extracellular matrix, neurovascular pathways, etc.) gives better results.
    Methods: We aim to leverage the benefits of constraining donor myogenic cells within a template that resembles muscle tissue. In this paper, we present a workflow for basic and translational studies aimed at promoting donor-cell-derived myogenesis to increase functional muscle mass in mice. Our workflow involves preparing a slurry of 10% sodium alginate mixed with myogenic cells in cell culture media, extruding the cell-containing slurry into 10% calcium lactate to form tubes, and implanting the cellularized alginate tubes into host muscle.
    Results: Our data suggest that, the extruded alginate tubes can tolerate a peak stress of 1892 ± 527 mN, that the elastic range is at ~75-125% strain beyond initial length, and that the Young's modulus (stiffness) is 14.17 ± 1.68 %/mm
    Discussion: This pilot study is limited in its translational scope because it was performed in vitro and with previously euthanized mice. Additional studies are needed to confirm that cellularized alginate tubes can promote the de novo development of donor-cell-derived muscle fibers, which can contribute to contractile force production.
    Conclusion: Alginate tubes with MuSC/myoblasts can be generated by a simple extrusion method. The alginate tubes have sufficient mechanical strength to tolerate insertion into a host muscle, in a minimally-invasive manner, through a needle track. The cellularized alginate tubes demonstrate myogenic potential since they are capable of being maintained in culture conditions for several days, after which they can still facilitate myoblast outgrowth in a dish.
    Language English
    Publishing date 2024-05-03
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.04.30.591971
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Women's Lives Matter-The Critical Need for Women to Prioritize Optimal Physical Activity to Reduce COVID-19 Illness Risk and Severity.

    Garcia-Pelagio, Karla P / Hew-Butler, Tamara / Fahlman, Mariane M / Roche, Joseph A

    International journal of environmental research and public health

    2021  Volume 18, Issue 19

    Abstract: Physical activity (PA) is beneficial for the health and wellness of individuals and societies. During an infectious disease pandemic, such as the one caused by COVID-19, social distancing, quarantines, and lockdowns are used to reduce community spread of ...

    Abstract Physical activity (PA) is beneficial for the health and wellness of individuals and societies. During an infectious disease pandemic, such as the one caused by COVID-19, social distancing, quarantines, and lockdowns are used to reduce community spread of the disease. Unfortunately, such nonpharmacological interventions or physical risk mitigation measures also make it challenging to engage in PA. Reduced PA could then trigger physiological changes that affect both mental and physical health. In this regard, women are more likely to experience physical and psychological distress. PA is a safe and effective nonpharmacological modality that can help prevent and manage several mental and physical health problems when performed correctly. PA might even confer benefits that are directly related to decreasing COVID-19 morbidity and mortality in women. In this review, we summarize why optimal PA must be a priority for women during the COVID-19 pandemic. We then discuss chronic COVID-19 illness and its impact on women, which further underscores the need for worldwide preventive health strategies that include PA. Finally, we discuss the importance of vaccination against COVID-19 for women, as part of prioritizing preventive healthcare and an active lifestyle.
    MeSH term(s) COVID-19 ; Communicable Disease Control ; Exercise ; Female ; Humans ; Pandemics ; SARS-CoV-2
    Language English
    Publishing date 2021-09-29
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2175195-X
    ISSN 1660-4601 ; 1661-7827
    ISSN (online) 1660-4601
    ISSN 1661-7827
    DOI 10.3390/ijerph181910271
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Minimally invasive muscle embedding (mime) - a novel experimental technique to facilitate donor-cell-mediated myogenesis

    Roche, Joseph A / Begam, Morium / Galen, Sujay S

    Journal of visualized experiments. 2017 Aug. 24, , no. 126

    2017  

    Abstract: Skeletal muscle possesses regenerative capacity due to tissue-resident, muscle-fiber-generating (myogenic) satellite cells (SCs), which can form new muscle fibers under the right conditions. Although SCs can be harvested from muscle tissue and cultured ... ...

    Abstract Skeletal muscle possesses regenerative capacity due to tissue-resident, muscle-fiber-generating (myogenic) satellite cells (SCs), which can form new muscle fibers under the right conditions. Although SCs can be harvested from muscle tissue and cultured in vitro, the resulting myoblast cells are not very effective in promoting myogenesis when transplanted into host muscle. Surgically exposing the host muscle and grafting segments of donor muscle tissue, or the isolated muscle fibers with their SCs onto host muscle, promotes better myogenesis compared to myoblast transplantation. We have developed a novel technique that we call Minimally Invasive Muscle Embedding (MIME). MIME involves passing a surgical needle through the host muscle, drawing a piece of donor muscle tissue through the needle track, and then leaving the donor tissue embedded in the host muscle so that it may act as a source of SCs for the host muscle. Here we describe in detail the steps involved in performing MIME in an immunodeficient mouse model that expresses a green fluorescent protein (GFP) in all of its cells. Immunodeficiency in the host mouse reduces the risk of immune rejection of the donor tissue, and GFP expression enables easy identification of the host muscle fibers (GFP+) and donor-cell-derived muscle fibers (GFP-). Our pilot data suggest that MIME can be used to implant an extensor digitorum longus (EDL) muscle from a donor mouse into the tibialis anterior (TA) muscle of a host mouse. Our data also suggest that when a myotoxin (barium chloride, BaCl2) is injected into the host muscle after MIME, there is evidence of donor-cell-derived myogenesis in the host muscle, with approximately 5%, 26%, 26% and 43% of the fibers in a single host TA muscle showing no host contribution, minimal host contribution, moderate host contribution, and maximal host contribution, respectively.
    Keywords animal models ; barium ; green fluorescent protein ; immunosuppression ; mice ; muscle development ; muscle fibers ; muscles ; myoblasts ; risk reduction ; skeletal muscle
    Language English
    Dates of publication 2017-0824
    Size p. e55731.
    Publishing place Journal of Visualized Experiments
    Document type Article
    ZDB-ID 2259946-0
    ISSN 1940-087X
    ISSN 1940-087X
    DOI 10.3791/55731
    Database NAL-Catalogue (AGRICOLA)

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  10. Article ; Online: Minimally Invasive Muscle Embedding (MIME) - A Novel Experimental Technique to Facilitate Donor-Cell-Mediated Myogenesis.

    Roche, Joseph A / Begam, Morium / Galen, Sujay S

    Journal of visualized experiments : JoVE

    2017  , Issue 126

    Abstract: Skeletal muscle possesses regenerative capacity due to tissue-resident, muscle-fiber-generating (myogenic) satellite cells (SCs), which can form new muscle fibers under the right conditions. Although SCs can be harvested from muscle tissue and cultured ... ...

    Abstract Skeletal muscle possesses regenerative capacity due to tissue-resident, muscle-fiber-generating (myogenic) satellite cells (SCs), which can form new muscle fibers under the right conditions. Although SCs can be harvested from muscle tissue and cultured in vitro, the resulting myoblast cells are not very effective in promoting myogenesis when transplanted into host muscle. Surgically exposing the host muscle and grafting segments of donor muscle tissue, or the isolated muscle fibers with their SCs onto host muscle, promotes better myogenesis compared to myoblast transplantation. We have developed a novel technique that we call Minimally Invasive Muscle Embedding (MIME). MIME involves passing a surgical needle through the host muscle, drawing a piece of donor muscle tissue through the needle track, and then leaving the donor tissue embedded in the host muscle so that it may act as a source of SCs for the host muscle. Here we describe in detail the steps involved in performing MIME in an immunodeficient mouse model that expresses a green fluorescent protein (GFP) in all of its cells. Immunodeficiency in the host mouse reduces the risk of immune rejection of the donor tissue, and GFP expression enables easy identification of the host muscle fibers (GFP+) and donor-cell-derived muscle fibers (GFP-). Our pilot data suggest that MIME can be used to implant an extensor digitorum longus (EDL) muscle from a donor mouse into the tibialis anterior (TA) muscle of a host mouse. Our data also suggest that when a myotoxin (barium chloride, BaCl2) is injected into the host muscle after MIME, there is evidence of donor-cell-derived myogenesis in the host muscle, with approximately 5%, 26%, 26% and 43% of the fibers in a single host TA muscle showing no host contribution, minimal host contribution, moderate host contribution, and maximal host contribution, respectively.
    Language English
    Publishing date 2017-08-24
    Publishing country United States
    Document type Journal Article
    ISSN 1940-087X
    ISSN (online) 1940-087X
    DOI 10.3791/55731
    Database MEDical Literature Analysis and Retrieval System OnLINE

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