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  1. Article: Effects of Pharmacological Inhibitors of NADPH Oxidase on Myogenic Contractility and Evoked Vasoactive Responses in Rat Resistance Arteries.

    Kendrick, Dylan J / Mishra, Ramesh C / John, Cini Mathew / Zhu, Hai-Lei / Braun, Andrew P

    Frontiers in physiology

    2022  Volume 12, Page(s) 752366

    Abstract: Reactive oxygen species (ROS), such as superoxide anions and hydrogen peroxide, are reported to contribute to the dynamic regulation of contractility in various arterial preparations, however, the situation in pressurized, myogenically active resistance ... ...

    Abstract Reactive oxygen species (ROS), such as superoxide anions and hydrogen peroxide, are reported to contribute to the dynamic regulation of contractility in various arterial preparations, however, the situation in pressurized, myogenically active resistance arteries is much less clear. In the present study, we have utilized established pharmacological inhibitors of NADPH oxidase activity to examine the potential contribution of ROS to intrinsic myogenic contractility in adult Sprague-Dawley rat resistance arteries and responses to vasoactive agents acting
    Language English
    Publishing date 2022-01-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2021.752366
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: High-titer manufacturing of SARS-CoV-2 Spike-pseudotyped VSV in stirred-tank bioreactors.

    Todesco, Hayley M / Gafuik, Chris / John, Cini M / Roberts, Erin L / Borys, Breanna S / Pawluk, Alexis / Kallos, Michael S / Potts, Kyle G / Mahoney, Douglas J

    Molecular therapy. Methods & clinical development

    2024  Volume 32, Issue 1, Page(s) 101189

    Abstract: The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic highlighted the importance of vaccine innovation in public health. Hundreds of vaccines built on numerous technology platforms have been rapidly developed against SARS-CoV-2 since ... ...

    Abstract The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic highlighted the importance of vaccine innovation in public health. Hundreds of vaccines built on numerous technology platforms have been rapidly developed against SARS-CoV-2 since 2020. Like all vaccine platforms, an important bottleneck to viral-vectored vaccine development is manufacturing. Here, we describe a scalable manufacturing protocol for replication-competent SARS-CoV-2 Spike-pseudotyped vesicular stomatitis virus (S-VSV)-vectored vaccines using Vero cells grown on microcarriers in a stirred-tank bioreactor. Using Cytodex 1 microcarriers over 6 days of fed-batch culture, Vero cells grew to a density of 3.95 ± 0.42 ×10
    Language English
    Publishing date 2024-01-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2872938-9
    ISSN 2329-0501 ; 2329-0501
    ISSN (online) 2329-0501
    ISSN 2329-0501
    DOI 10.1016/j.omtm.2024.101189
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  3. Article ; Online: SKA-31, an activator of endothelial Ca

    Khaddaj-Mallat, Rayan / Mathew John, Cini / Braun, Andrew P

    European journal of pharmacology

    2018  Volume 831, Page(s) 60–67

    Abstract: It is now well recognized that endothelial KCa2.3 and KCa3.1 channel activities contribute to dilation of resistance arteries via endothelium-mediated hyperpolarization and vascular smooth muscle relaxation. In this study, we have investigated the ... ...

    Abstract It is now well recognized that endothelial KCa2.3 and KCa3.1 channel activities contribute to dilation of resistance arteries via endothelium-mediated hyperpolarization and vascular smooth muscle relaxation. In this study, we have investigated the functional effect of the KCa channel activator SKA-31 in third order rat mesenteric arteries using arterial pressure myography. Isolated arteries were cannulated, pressurized intraluminally to 70 mmHg at 36 °C and then constricted with 1 μM phenylephrine. Acute bath exposure to SKA-31 evoked a robust and reversible inhibition of developed tone (IC
    MeSH term(s) Animals ; Benzothiazoles/pharmacology ; Dose-Response Relationship, Drug ; In Vitro Techniques ; Intermediate-Conductance Calcium-Activated Potassium Channels/agonists ; Intermediate-Conductance Calcium-Activated Potassium Channels/genetics ; Intermediate-Conductance Calcium-Activated Potassium Channels/metabolism ; Male ; Mesenteric Arteries/drug effects ; Mesenteric Arteries/metabolism ; Myography ; Rats, Sprague-Dawley ; Signal Transduction/drug effects ; Small-Conductance Calcium-Activated Potassium Channels/agonists ; Small-Conductance Calcium-Activated Potassium Channels/genetics ; Small-Conductance Calcium-Activated Potassium Channels/metabolism ; Vasodilation/drug effects ; Vasodilator Agents/pharmacology
    Chemical Substances Benzothiazoles ; Intermediate-Conductance Calcium-Activated Potassium Channels ; Kcnn3 protein, rat ; Kcnn4 protein, rat ; Small-Conductance Calcium-Activated Potassium Channels ; Vasodilator Agents ; naphtho(1,2-d)thiazol-2-ylamine
    Language English
    Publishing date 2018-05-09
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 80121-5
    ISSN 1879-0712 ; 0014-2999
    ISSN (online) 1879-0712
    ISSN 0014-2999
    DOI 10.1016/j.ejphar.2018.05.006
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  4. Article ; Online: Pharmacological Targeting of KCa Channels to Improve Endothelial Function in the Spontaneously Hypertensive Rat.

    Khaddaj Mallat, Rayan / Mathew John, Cini / Mishra, Ramesh C / Kendrick, Dylan J / Braun, Andrew P

    International journal of molecular sciences

    2019  Volume 20, Issue 14

    Abstract: Systemic hypertension is a major risk factor for the development of cardiovascular disease and is often associated with endothelial dysfunction. KCa2.3 and KCa3.1 channels are expressed in the vascular endothelium and contribute to stimulus-evoked ... ...

    Abstract Systemic hypertension is a major risk factor for the development of cardiovascular disease and is often associated with endothelial dysfunction. KCa2.3 and KCa3.1 channels are expressed in the vascular endothelium and contribute to stimulus-evoked vasodilation. We hypothesized that acute treatment with SKA-31, a selective activator of KCa2.x and KCa3.1 channels, would improve endothelium-dependent vasodilation and transiently lower mean arterial pressure (MAP) in male, spontaneously hypertensive rats (SHRs). Isolated vascular preparations exhibited impaired vasodilation in response to bradykinin (i.e., endothelial dysfunction) compared with Wistar controls, which was associated with decreased bradykinin receptor expression in mesenteric arteries. In contrast, similar levels of endothelial KCa channel expression were observed, and SKA-31 evoked vasodilation was comparable in vascular preparations from both strains. Addition of a low concentration of SKA-31 (i.e., 0.2-0.3 μM) failed to augment bradykinin-induced vasodilation in arteries from SHRs. However, responses to acetylcholine were enhanced. Surprisingly, acute bolus administration of SKA-31 in vivo (30 mg/kg, i.p. injection) modestly elevated MAP compared with vehicle injection. In summary, pharmacological targeting of endothelial KCa channels in SHRs did not readily reverse endothelial dysfunction in situ, or lower MAP in vivo. SHRs thus appear to be less responsive to endothelial KCa channel activators, which may be related to their vascular pathology.
    MeSH term(s) Acetylcholine/pharmacology ; Animals ; Benzothiazoles/pharmacology ; Benzothiazoles/therapeutic use ; Blood Pressure ; Bradykinin/pharmacology ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/physiopathology ; Hypertension/drug therapy ; Hypertension/physiopathology ; Intermediate-Conductance Calcium-Activated Potassium Channels/agonists ; Intermediate-Conductance Calcium-Activated Potassium Channels/metabolism ; Male ; Rats ; Rats, Inbred SHR ; Rats, Wistar ; Receptors, Bradykinin/genetics ; Receptors, Bradykinin/metabolism ; Vasodilation
    Chemical Substances Benzothiazoles ; Intermediate-Conductance Calcium-Activated Potassium Channels ; Receptors, Bradykinin ; naphtho(1,2-d)thiazol-2-ylamine ; Acetylcholine (N9YNS0M02X) ; Bradykinin (S8TIM42R2W)
    Language English
    Publishing date 2019-07-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms20143481
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  5. Article ; Online: Human mesenchymal stem cells inhibit the differentiation and effector functions of monocytes.

    Maqbool, Maryam / Algraittee, Satar Jabbar Rahi / Boroojerdi, Mohadese Hashem / Sarmadi, Vahid Hosseinpour / John, Cini Mathew / Vidyadaran, Sharmili / Ramasamy, Rajesh

    Innate immunity

    2020  Volume 26, Issue 5, Page(s) 424–434

    Abstract: Although monocytes represent an essential part of the host defence system, their accumulation and prolonged stimulation could be detrimental and may aggravate chronic inflammatory diseases. The present study has explored the less-understood ... ...

    Abstract Although monocytes represent an essential part of the host defence system, their accumulation and prolonged stimulation could be detrimental and may aggravate chronic inflammatory diseases. The present study has explored the less-understood immunomodulatory effects of mesenchymal stem cells on monocyte functions. Isolated purified human monocytes were co-cultured with human umbilical cord-derived mesenchymal stem cells under appropriate culture conditions to assess monocytes' vital functions. Based on the surface marker analysis, mesenchymal stem cells halted monocyte differentiation into dendritic cells and macrophages and reduced their phagocytosis functions, which rendered an inability to stimulate T-cell proliferation. The present study confers that mesenchymal stem cells exerted potent immunosuppressive activity on monocyte functions such as differentiation, phagocytosis and Ag presentation; hence, they promise a potential therapeutic role in down-regulating the unwanted monocyte-mediated immune responses in the context of chronic inflammatory diseases.
    MeSH term(s) Antigen Presentation ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Coculture Techniques ; Dendritic Cells/immunology ; Humans ; Immunomodulation ; Immunotherapy/methods ; Inflammation/immunology ; Inflammation/therapy ; Lymphocyte Activation ; Macrophages/immunology ; Mesenchymal Stem Cells/physiology ; Monocytes/immunology ; Phagocytosis ; T-Lymphocytes/immunology ; Umbilical Cord/cytology
    Language English
    Publishing date 2020-07-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2381250-3
    ISSN 1753-4267 ; 1753-4259
    ISSN (online) 1753-4267
    ISSN 1753-4259
    DOI 10.1177/1753425919899132
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  6. Article ; Online: Maternal Cognitive Impairment Associated with Gestational Diabetes Mellitus-A Review of Potential Contributing Mechanisms.

    John, Cini Mathew / Mohamed Yusof, Nur Intan Saidaah / Abdul Aziz, Siti Hajar / Mohd Fauzi, Fazlin

    International journal of molecular sciences

    2018  Volume 19, Issue 12

    Abstract: Gestational diabetes mellitus (GDM) carries many risks, where high blood pressure, preeclampsia and future type II diabetes are widely acknowledged, but less focus has been placed on its effect on cognitive function. Although the multifactorial ... ...

    Abstract Gestational diabetes mellitus (GDM) carries many risks, where high blood pressure, preeclampsia and future type II diabetes are widely acknowledged, but less focus has been placed on its effect on cognitive function. Although the multifactorial pathogenesis of maternal cognitive impairment is not completely understood, it shares several features with type 2 diabetes mellitus (T2DM). In this review, we discuss some key pathophysiologies of GDM that may lead to cognitive impairment, specifically hyperglycemia, insulin resistance, oxidative stress, and neuroinflammation. We explain how these incidents: (i) impair the insulin-signaling pathway and/or (ii) lead to cognitive impairment through hyperphosphorylation of τ protein, overexpression of amyloid-β and/or activation of microglia. The aforementioned pathologies impair the insulin-signaling pathway primarily through serine phosphorylation of insulin receptor substances (IRS). This then leads to the inactivation of the phosphatidylinositol 3-kinase/Protein kinase B (PI3K/AKT) signaling cascade, which is responsible for maintaining brain homeostasis and normal cognitive functioning. PI3K/AKT is crucial in maintaining normal cognitive function through the inactivation of glycogen synthase kinase 3β (GSκ3β), which hyperphosphorylates τ protein and releases pro-inflammatory cytokines that are neurotoxic. Several biomarkers were also highlighted as potential biomarkers of GDM-related cognitive impairment such as AGEs, serine-phosphorylated IRS-1 and inflammatory markers such as tumor necrosis factor α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), leptin, interleukin 1β (IL-1β), and IL-6. Although GDM is a transient disease, its complications may be long-term, and hence increased mechanistic knowledge of the molecular changes contributing to cognitive impairment may provide important clues for interventional strategies.
    MeSH term(s) Amyloid beta-Peptides/metabolism ; Cognitive Dysfunction/metabolism ; Cognitive Dysfunction/pathology ; Diabetes, Gestational/metabolism ; Diabetes, Gestational/pathology ; Female ; Glycogen Synthase Kinase 3 beta/metabolism ; Humans ; Interleukin-1beta/metabolism ; Interleukin-6/metabolism ; Microglia/metabolism ; Microglia/pathology ; Phosphatidylinositol 3-Kinases/metabolism ; Pregnancy ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction
    Chemical Substances Amyloid beta-Peptides ; IL1B protein, human ; IL6 protein, human ; Interleukin-1beta ; Interleukin-6 ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; GSK3B protein, human (EC 2.7.11.1) ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
    Language English
    Publishing date 2018-12-05
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms19123894
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  7. Article ; Online: Programming of Vascular Dysfunction in the Intrauterine Milieu of Diabetic Pregnancies.

    Sallam, Nada A / Palmgren, Victoria A C / Singh, Radha D / John, Cini M / Thompson, Jennifer A

    International journal of molecular sciences

    2018  Volume 19, Issue 11

    Abstract: With the rising global tide of obesity, gestational diabetes mellitus (GDM) burgeoned into one of the most common antenatal disorders worldwide. Macrosomic babies born to diabetic mothers are more likely to develop risk factors for cardiovascular disease ...

    Abstract With the rising global tide of obesity, gestational diabetes mellitus (GDM) burgeoned into one of the most common antenatal disorders worldwide. Macrosomic babies born to diabetic mothers are more likely to develop risk factors for cardiovascular disease (CVD) before they reach adulthood. Rodent studies in offspring born to hyperglycemic pregnancies show vascular dysfunction characterized by impaired nitric oxide (NO)-mediated vasodilation and increased production of contractile prostanoids by cyclooxygenase 2 (COX-2). Vascular dysfunction is a key pathogenic event in the progression of diabetes-related vascular disease, primarily attributable to glucotoxicity. Therefore, glucose-induced vascular injury may stem directly from the hyperglycemic intrauterine environment of GDM pregnancy, as evinced by studies showing endothelial activation and inflammation at birth or in childhood in offspring born to GDM mothers. This review discusses potential mechanisms by which intrauterine hyperglycemia programs dysfunction in the developing vasculature.
    MeSH term(s) Animals ; Diabetes, Gestational/epidemiology ; Diabetes, Gestational/genetics ; Diabetes, Gestational/physiopathology ; Diabetic Angiopathies/epidemiology ; Diabetic Angiopathies/genetics ; Diabetic Angiopathies/physiopathology ; Epigenesis, Genetic ; Female ; Humans ; Oxidative Stress ; Pregnancy ; Risk Factors ; Uterus/metabolism ; Uterus/physiopathology
    Language English
    Publishing date 2018-11-20
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms19113665
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  8. Article ; Online: The vascular endothelium: A regulator of arterial tone and interface for the immune system.

    Khaddaj Mallat, Rayan / Mathew John, Cini / Kendrick, Dylan J / Braun, Andrew P

    Critical reviews in clinical laboratory sciences

    2017  , Page(s) 1–13

    Abstract: As the primary interface between the blood and various tissues of the body, the vascular endothelium exhibits a diverse range of roles and activities, all of which contribute to the overall health and function of the cardiovascular system. In this ... ...

    Abstract As the primary interface between the blood and various tissues of the body, the vascular endothelium exhibits a diverse range of roles and activities, all of which contribute to the overall health and function of the cardiovascular system. In this focused review, we discuss several key aspects of endothelial function, how this may be compromised and subsequent consequences. Specifically, we examine the dynamic regulation of arterial contractility and distribution of blood flow through the generation of chemical and electrical signaling events that impinge upon vascular smooth muscle. The endothelium can generate a diverse range of vasoactive compounds and signals, most of which act locally to adjust blood flow in a dynamic fashion to match tissue metabolism. Disruption of these vascular signaling processes (e.g. reduced nitric oxide bioavailability) is typically referred to as endothelial dysfunction, which is a recognized risk factor for cardiovascular disease in patients and occurs early in the development and progression of hypertension, atherosclerosis and tissue ischemia. Endothelial dysfunction is also associated with type-2 Diabetes and aging and increased mechanistic knowledge of the cellular changes contributing to these effects may provide important clues for interventional strategies. The endothelium also serves as the initial site of interaction for immune cells entering tissues in response to damage and acts to facilitate the actions of both the innate and acquired immune systems to interact with the vascular wall. In addition to representing the main cell type responsible for the formation of new blood vessels (i.e. angiogenesis) within the vasculature, the endothelium is also emerging as a source of extracellular vesicle or microparticles for the transport of signaling molecules and other cellular materials to nearby, or remote, sites in the body. The characteristics of released microparticles appear to change with the functional status of the endothelium; thus, these microparticles may represent novel biomarkers of endothelial health and more serious cardiovascular disease.
    Language English
    Publishing date 2017-10-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 280641-1
    ISSN 1549-781X ; 1040-8363 ; 0590-8191
    ISSN (online) 1549-781X
    ISSN 1040-8363 ; 0590-8191
    DOI 10.1080/10408363.2017.1394267
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  9. Article ; Online: Pharmacologic targeting of endothelial Ca

    Mathew John, Cini / Khaddaj Mallat, Rayan / George, Grace / Kim, Taeyeob / Mishra, Ramesh C / Braun, Andrew P

    Channels (Austin, Tex.)

    2018  Volume 12, Issue 1, Page(s) 126–136

    Abstract: Endothelial small and intermediate-conductance, ... ...

    Abstract Endothelial small and intermediate-conductance, Ca
    MeSH term(s) Animals ; Benzothiazoles/pharmacology ; Cardiovascular System/drug effects ; Cardiovascular System/metabolism ; Endothelial Cells/drug effects ; Endothelial Cells/metabolism ; Humans ; Potassium Channels, Calcium-Activated/antagonists & inhibitors ; Potassium Channels, Calcium-Activated/metabolism
    Chemical Substances Benzothiazoles ; Potassium Channels, Calcium-Activated ; naphtho(1,2-d)thiazol-2-ylamine
    Language English
    Publishing date 2018-03-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2262854-X
    ISSN 1933-6969 ; 1933-6969
    ISSN (online) 1933-6969
    ISSN 1933-6969
    DOI 10.1080/19336950.2018.1454814
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  10. Article ; Online: Human Mesenchymal Stem Cells-mediated Transcriptomic Regulation of Leukemic Cells in Delivering Anti-tumorigenic Effects.

    Sarmadi, Vahid Hosseinpour / Ahmadloo, Salma / Boroojerdi, Mohadese Hashem / John, Cini Mathew / Al-Graitte, Satar Jabbar Rahi / Lawal, Hamza / Maqbool, Maryam / Hwa, Ling King / Ramasamy, Rajesh

    Cell transplantation

    2020  Volume 29, Page(s) 963689719885077

    Abstract: Treatment of leukemia has become much difficult because of resistance to the existing anticancer therapies. This has thus expedited the search for alternativ therapies, and one of these is the exploitation of mesenchymal stem cells (MSCs) towards control ...

    Abstract Treatment of leukemia has become much difficult because of resistance to the existing anticancer therapies. This has thus expedited the search for alternativ therapies, and one of these is the exploitation of mesenchymal stem cells (MSCs) towards control of tumor cells. The present study investigated the effect of human umbilical cord-derived MSCs (UC-MSCs) on the proliferation of leukemic cells and gauged the transcriptomic modulation and the signaling pathways potentially affected by UC-MSCs. The inhibition of growth of leukemic tumor cell lines was assessed by proliferation assays, apoptosis and cell cycle analysis. BV173 and HL-60 cells were further analyzed using microarray gene expression profiling. The microarray results were validated by RT-qPCR and western blot assay for the corresponding expression of genes and proteins. The UC-MSCs attenuated leukemic cell viability and proliferation in a dose-dependent manner without inducing apoptosis. Cell cycle analysis revealed that the growth of tumor cells was arrested at the G
    MeSH term(s) Apoptosis/genetics ; Apoptosis/physiology ; Cell Cycle/genetics ; Cell Cycle/physiology ; Cell Line, Tumor ; Cell Proliferation/genetics ; Cell Proliferation/physiology ; Gene Expression Profiling ; Gene Ontology ; HL-60 Cells ; Humans ; Leukemia/metabolism ; Leukemia/pathology ; Mesenchymal Stem Cells/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Umbilical Cord/cytology
    Language English
    Publishing date 2020-02-04
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1135816-6
    ISSN 1555-3892 ; 0963-6897
    ISSN (online) 1555-3892
    ISSN 0963-6897
    DOI 10.1177/0963689719885077
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