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  1. AU="Srivastava, Rupesh"
  2. AU="Nathan, Jaimie D"
  3. AU="Schnegelberger, Regina D"
  4. AU=Doshi Paresh
  5. AU="Cecilia Hognon"
  6. AU="Mason, Jeremy K."
  7. AU=Hasumi Hisashi
  8. AU="Swati Sethi"
  9. AU="Martin G. Myers, Jr."
  10. AU="Marcus-Sekura, Carol"
  11. AU="Petagine, Lucy"
  12. AU="Jessa R. Alexander"
  13. AU=Rauner Martina
  14. AU="Richlen, Mindy L"
  15. AU="Merghani, Nada M"
  16. AU=Splitt M P
  17. AU="Zlatanović, Gordana"

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  1. Artikel: The Rising Era of "Immunoporosis": Role of Immune System in the Pathophysiology of Osteoporosis.

    Srivastava, Rupesh K / Sapra, Leena

    Journal of inflammation research

    2022  Band 15, Seite(n) 1667–1698

    Abstract: Discoveries in the last few years have emphasized the existence of an enormous breadth of communication between bone and the immune system in maintaining skeletal homeostasis. Originally, the discovery of various factors was assigned to the immune system ...

    Abstract Discoveries in the last few years have emphasized the existence of an enormous breadth of communication between bone and the immune system in maintaining skeletal homeostasis. Originally, the discovery of various factors was assigned to the immune system viz. interleukin (IL)-6, IL-10, IL-17, tumor necrosis factor (TNF)-α, receptor activator of nuclear factor kappa B ligand (RANKL), nuclear factor of activated T cells (NFATc1), etc., but now these factors have also been shown to have a significant impact on osteoblasts (OBs) and osteoclasts (OCs) biology. These discoveries led to an alteration in the approach for the treatment of several bone pathologies including osteoporosis. Osteoporosis is an inflammatory bone anomaly affecting more than 500 million people globally. In 2018, to highlight the importance of the immune system in the pathophysiology of osteoporosis, our group coined the term "immunoporosis". In the present review, we exhaustively revisit the characteristics, mechanism of action, and function of both innate and adaptive immune cells with the goal of understanding the potential of immune cells in osteoporosis. We also highlight the Immunoporotic role of gut microbiota (GM) for the treatment and management of osteoporosis. Importantly, we further discuss whether an immune cell-based strategy to treat and manage osteoporosis is feasible and relevant in clinical settings.
    Sprache Englisch
    Erscheinungsdatum 2022-03-05
    Erscheinungsland New Zealand
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2494878-0
    ISSN 1178-7031
    ISSN 1178-7031
    DOI 10.2147/JIR.S351918
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  2. Artikel: Editorial: Gut microbiota and gut-associated metabolites in bone health.

    Srivastava, Rupesh K / Duggal, Niharika Arora / Parameswaran, Narayanan

    Frontiers in endocrinology

    2023  Band 14, Seite(n) 1232050

    Mesh-Begriff(e) Humans ; Gastrointestinal Microbiome ; Bone Density ; Inflammation ; Arthritis, Rheumatoid ; Bone and Bones
    Sprache Englisch
    Erscheinungsdatum 2023-07-20
    Erscheinungsland Switzerland
    Dokumenttyp Editorial
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2023.1232050
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  3. Artikel ; Online: High Salt Diet Impairs Male Fertility in Mice via Modulating the Skeletal Homeostasis.

    Saugandhika, Shrabani / Sapra, Leena / Kumari, Kiran / Srivastava, Rupesh K

    Reproductive sciences (Thousand Oaks, Calif.)

    2023  Band 30, Heft 11, Seite(n) 3339–3352

    Abstract: Male reproductive functions and bone health are both adversely affected by the high salt diet (HSD). Nevertheless, the underlying mechanism via which it alters the sperm function remains largely unknown. This study examines the mechanism by which HSD ... ...

    Abstract Male reproductive functions and bone health are both adversely affected by the high salt diet (HSD). Nevertheless, the underlying mechanism via which it alters the sperm function remains largely unknown. This study examines the mechanism by which HSD affects male fertility by impairing bone health. For investigating the same, male BALB/c mice were categorized into three groups-HSD group (fed with 4% NaCl), a low salt diet (LSD) group (fed with 0.4% NaCl), and a control group (fed with a normal diet) for 6 weeks and thereafter assessed for various sperm parameters, bone turnover markers, and testosterone levels. Furthermore, the quantitative assessment of testosterone biosynthesis enzymes was performed. Interestingly, we observed that mice fed with HSD showed significant alterations in sperm parameters-motility, count, and vitality, including morphological changes compared to both the LSD and the control groups. In addition, serum analysis showed an increase in bone resorption markers and a decrease in bone formation markers in the HSD group (p < 0.05). Further, HSD caused a decrease in the testosterone level and mRNA expression of testosterone biosynthesis enzymes. Importantly, a significant decrease in bone formation marker osteocalcin (OC) was observed to coincide with the dip in testosterone level in the HSD group. Given that OC plays a key role in maintaining male fertility, the above findings suggest that a decrease in OC levels may affect the testosterone biosynthesis pathway, reducing testosterone hormone secretion and thereby resulting in decreased spermatogenesis. The study for the first time delineates and bridges the mechanism of HSD-mediated bone loss (results in a deficiency of OC) with decreased testosterone biosynthesis and thus impaired male fertility.
    Mesh-Begriff(e) Mice ; Male ; Animals ; Sodium Chloride/metabolism ; Semen/metabolism ; Testosterone ; Sodium Chloride, Dietary/adverse effects ; Fertility ; Diet/adverse effects ; Homeostasis ; Testis/metabolism
    Chemische Substanzen Sodium Chloride (451W47IQ8X) ; Testosterone (3XMK78S47O) ; Sodium Chloride, Dietary
    Sprache Englisch
    Erscheinungsdatum 2023-06-15
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2276411-2
    ISSN 1933-7205 ; 1933-7191
    ISSN (online) 1933-7205
    ISSN 1933-7191
    DOI 10.1007/s43032-023-01278-w
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  4. Artikel ; Online: Osteometabolism: Metabolic Alterations in Bone Pathologies.

    Srivastava, Rupesh K / Sapra, Leena / Mishra, Pradyumna K

    Cells

    2022  Band 11, Heft 23

    Abstract: Renewing interest in the study of intermediate metabolism and cellular bioenergetics is brought on by the global increase in the prevalence of metabolic illnesses. Understanding of the mechanisms that integrate energy metabolism in the entire organism ... ...

    Abstract Renewing interest in the study of intermediate metabolism and cellular bioenergetics is brought on by the global increase in the prevalence of metabolic illnesses. Understanding of the mechanisms that integrate energy metabolism in the entire organism has significantly improved with the application of contemporary biochemical tools for quantifying the fuel substrate metabolism with cutting-edge mouse genetic procedures. Several unexpected findings in genetically altered mice have prompted research into the direction of intermediate metabolism of skeletal cells. These findings point to the possibility of novel endocrine connections through which bone cells can convey their energy status to other metabolic control centers. Understanding the expanded function of skeleton system has in turn inspired new lines of research aimed at characterizing the energy needs and bioenergetic characteristics of these bone cells. Bone-forming osteoblast and bone-resorbing osteoclast cells require a constant and large supply of energy substrates such as glucose, fatty acids, glutamine, etc., for their differentiation and functional activity. According to latest research, important developmental signaling pathways in bone cells are connected to bioenergetic programs, which may accommodate variations in energy requirements during their life cycle. The present review article provides a unique perspective of the past and present research in the metabolic characteristics of bone cells along with mechanisms governing energy substrate utilization and bioenergetics. In addition, we discussed the therapeutic inventions which are currently being utilized for the treatment and management of bone-related diseases such as osteoporosis, rheumatoid arthritis (RA), osteogenesis imperfecta (OIM), etc., by modulating the energetics of bone cells. We further emphasized on the role of GUT-associated metabolites (GAMs) such as short-chain fatty acids (SCFAs), medium-chain fatty acids (MCFAs), indole derivates, bile acids, etc., in regulating the energetics of bone cells and their plausible role in maintaining bone health. Emphasis is importantly placed on highlighting knowledge gaps in this novel field of skeletal biology, i.e., "Osteometabolism" (proposed by our group) that need to be further explored to characterize the physiological importance of skeletal cell bioenergetics in the context of human health and bone related metabolic diseases.
    Sprache Englisch
    Erscheinungsdatum 2022-12-06
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells11233943
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  5. Artikel: How Losing Sleep Following Vaccination May Weaken the Response to SARS-CoV Vaccines.

    Akhtar, Nasreen / Srivastava, Rupesh K / Shrivastava, Deepak

    Sleep and vigilance

    2022  Band 6, Heft 1, Seite(n) 249–251

    Abstract: With the emergence of new SARS-CoV-2 variants, a close analysis of factors that affect the efficacy of the vaccine in different groups is a must. It is important to elucidate the role of clinical, behavioral and host factors on modulation of ... ...

    Abstract With the emergence of new SARS-CoV-2 variants, a close analysis of factors that affect the efficacy of the vaccine in different groups is a must. It is important to elucidate the role of clinical, behavioral and host factors on modulation of immunogenicity of the SARS-CoV-2 vaccine. Data from other vaccines have shown that duration and efficiency of sleep affect the immunogenicity of the vaccine. There is a need for identification of circadian influence and sleep on SARS-CoV-2 vaccine using validated immune correlates of protection. We propose that sleep acts as a natural adjuvant by promoting the immunological synapse formation between the antigen presenting cells and CD4
    Sprache Englisch
    Erscheinungsdatum 2022-02-17
    Erscheinungsland Singapore
    Dokumenttyp Journal Article
    ISSN 2510-2265
    ISSN 2510-2265
    DOI 10.1007/s41782-022-00195-3
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  6. Buch ; Online: Multimeasurement Generative Models

    Saremi, Saeed / Srivastava, Rupesh Kumar

    2021  

    Abstract: We formally map the problem of sampling from an unknown distribution with a density in $\mathbb{R}^d$ to the problem of learning and sampling a smoother density in $\mathbb{R}^{Md}$ obtained by convolution with a fixed factorial kernel: the new density ... ...

    Abstract We formally map the problem of sampling from an unknown distribution with a density in $\mathbb{R}^d$ to the problem of learning and sampling a smoother density in $\mathbb{R}^{Md}$ obtained by convolution with a fixed factorial kernel: the new density is referred to as M-density and the kernel as multimeasurement noise model (MNM). The M-density in $\mathbb{R}^{Md}$ is smoother than the original density in $\mathbb{R}^d$, easier to learn and sample from, yet for large $M$ the two problems are mathematically equivalent since clean data can be estimated exactly given a multimeasurement noisy observation using the Bayes estimator. To formulate the problem, we derive the Bayes estimator for Poisson and Gaussian MNMs in closed form in terms of the unnormalized M-density. This leads to a simple least-squares objective for learning parametric energy and score functions. We present various parametrization schemes of interest including one in which studying Gaussian M-densities directly leads to multidenoising autoencoders--this is the first theoretical connection made between denoising autoencoders and empirical Bayes in the literature. Samples in $\mathbb{R}^d$ are obtained by walk-jump sampling (Saremi & Hyvarinen, 2019) via underdamped Langevin MCMC (walk) to sample from M-density and the multimeasurement Bayes estimation (jump). We study permutation invariant Gaussian M-densities on MNIST, CIFAR-10, and FFHQ-256 datasets, and demonstrate the effectiveness of this framework for realizing fast-mixing stable Markov chains in high dimensions.

    Comment: Our code is publicly available at https://github.com/nnaisense/mems
    Schlagwörter Statistics - Machine Learning ; Computer Science - Machine Learning
    Thema/Rubrik (Code) 519
    Erscheinungsdatum 2021-12-17
    Erscheinungsland us
    Dokumenttyp Buch ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  7. Artikel ; Online: Synergistic correlation between host angiogenin and dengue virus replication.

    Madhry, Deeksha / Malvankar, Shivani / Phadnis, Sushant / Srivastava, Rupesh K / Bhattacharyya, Sankar / Verma, Bhupendra

    RNA biology

    2023  Band 20, Heft 1, Seite(n) 805–816

    Abstract: DENV infection poses a major health concern globally and the pathophysiology relies heavily on host-cellular machinery. Although virus replication relies heavily on the host, the mechanistic details of DENV-host interaction is not fully characterized yet. ...

    Abstract DENV infection poses a major health concern globally and the pathophysiology relies heavily on host-cellular machinery. Although virus replication relies heavily on the host, the mechanistic details of DENV-host interaction is not fully characterized yet. Here, we are focusing on characterizing the mechanistic basis of virus-induced stress on the host cell. Specifically, we aim to characterize the role of the stress modulator ribonuclease Angiogenin during DENV infection. Our results suggested that the levels of Angiogenin are up-regulated in DENV-infected cells and the levels increase proportionately with DENV replication. Our efforts to knockdown Angiogenin using siRNA were unsuccessful in DENV-infected cells but not in mock-infected control. To further investigate the modulation between DENV replication and Angiogenin, we treated Huh7 cells with Ivermectin prior to DENV infection. Our results suggest a significant reduction in DENV replication specifically at the later stages as a consequence of Ivermectin treatment. Interestingly, Angiogenin levels were also found to be decreased proportionately. Our results suggest that Angiogenin modulation during DENV infection is important for DENV replication and pathogenesis.
    Mesh-Begriff(e) Humans ; Ivermectin/pharmacology ; Ribonuclease, Pancreatic/genetics ; Virus Replication ; Dengue
    Chemische Substanzen angiogenin (EC 3.1.27.-) ; Ivermectin (70288-86-7) ; Ribonuclease, Pancreatic (EC 3.1.27.5)
    Sprache Englisch
    Erscheinungsdatum 2023-10-05
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2159587-2
    ISSN 1555-8584 ; 1555-8584
    ISSN (online) 1555-8584
    ISSN 1555-8584
    DOI 10.1080/15476286.2023.2264003
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  8. Artikel ; Online: Fine-tuning osteoclastogenesis: An insight into the cellular and molecular regulation of osteoclastogenesis.

    Anwar, Aleena / Sapra, Leena / Gupta, Navita / Ojha, Rudra P / Verma, Bhupendra / Srivastava, Rupesh K

    Journal of cellular physiology

    2023  Band 238, Heft 7, Seite(n) 1431–1464

    Abstract: Osteoclasts, the bone-resorbing cells, are essential for the bone remodeling process and are involved in the pathophysiology of several bone-related diseases. The extensive corpus of in vitro research and crucial mouse model studies in the 1990s ... ...

    Abstract Osteoclasts, the bone-resorbing cells, are essential for the bone remodeling process and are involved in the pathophysiology of several bone-related diseases. The extensive corpus of in vitro research and crucial mouse model studies in the 1990s demonstrated the key roles of monocyte/macrophage colony-stimulating factor, receptor activator of nuclear factor kappa B ligand (RANKL) and integrin αvβ3 in osteoclast biology. Our knowledge of the molecular mechanisms by which these variables control osteoclast differentiation and function has significantly advanced in the first decade of this century. Recent developments have revealed a number of novel insights into the fundamental mechanisms governing the differentiation and functional activity of osteoclasts; however, these mechanisms have not yet been adequately documented. Thus, in the present review, we discuss various regulatory factors including local and hormonal factors, innate as well as adaptive immune cells, noncoding RNAs (ncRNAs), etc., in the molecular regulation of the intricate and tightly regulated process of osteoclastogenesis. ncRNAs have a critical role as epigenetic controllers of osteoclast physiologic activities, including differentiation and bone resorption. The primary ncRNAs, which include micro-RNAs, circular RNAs, and long noncoding RNAs, form a complex network that affects gene transcription activities associated with osteoclast biological activity. Greater knowledge of the involvement of ncRNAs in osteoclast biological activities will contribute to the treatment and management of several skeletal diseases such as osteoporosis, osteoarthritis, rheumatoid arthritis, etc. Moreover, we further outline potential therapies targeting these regulatory pathways of osteoclastogenesis in distinct bone pathologies.
    Mesh-Begriff(e) Animals ; Mice ; Osteogenesis/genetics ; Osteoclasts/metabolism ; Bone Resorption/pathology ; Cell Differentiation/genetics ; Osteoblasts/metabolism ; Bone Diseases/metabolism ; RANK Ligand/genetics ; RANK Ligand/metabolism
    Chemische Substanzen RANK Ligand
    Sprache Englisch
    Erscheinungsdatum 2023-05-14
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 3116-1
    ISSN 1097-4652 ; 0021-9541
    ISSN (online) 1097-4652
    ISSN 0021-9541
    DOI 10.1002/jcp.31036
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  9. Artikel: The SARS-CoV-2 UTR's Intrudes Host RBP's and Modulates Cellular Splicing.

    Singh, Anjali / Pandey, Kush Kumar / Agrawal, Shubham Kumar / Srivastava, Rupesh K / Bhattacharyya, Sankar / Verma, Bhupendra

    Advances in virology

    2023  Band 2023, Seite(n) 2995443

    Abstract: SARS-CoV-2 is a novel coronavirus that causes a potentially fatal respiratory disease known as coronavirus disease (COVID-19) and is responsible for the ongoing pandemic with increasing mortality. Understanding the host-virus interaction involved in SARS- ...

    Abstract SARS-CoV-2 is a novel coronavirus that causes a potentially fatal respiratory disease known as coronavirus disease (COVID-19) and is responsible for the ongoing pandemic with increasing mortality. Understanding the host-virus interaction involved in SARS-CoV-2 pathophysiology will enhance our understanding of the mechanistic basis of COVID-19 infection. The characterization of post-transcriptional gene regulatory networks, particularly pre-mRNA splicing, and the identification and characterization of host proteins interacting with the 5' and 3'UTRs of SARS-CoV-2 will improve our understanding of post-transcriptional gene regulation during SARS-CoV-2 pathogenesis. Here, we demonstrate that either SARS-CoV-2 infection or exogenous overexpression of the 5' and 3'UTRs of the viral genomic RNAs, results in reduced mRNA levels possibly due to modulation of host cell pre-mRNA splicing. Further, we have investigated the potential RNA-binding proteins interacting with the 5' and 3'UTRs, using
    Sprache Englisch
    Erscheinungsdatum 2023-04-05
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2625776-2
    ISSN 1687-8647 ; 1687-8639
    ISSN (online) 1687-8647
    ISSN 1687-8639
    DOI 10.1155/2023/2995443
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  10. Artikel ; Online: Unravelling the immunobiology of innate lymphoid cells (ILCs): Implications in health and disease.

    Srivastava, Rupesh K / Sapra, Leena / Bhardwaj, Asha / Mishra, Pradyumna K / Verma, Bhupendra / Baig, Zainab

    Cytokine & growth factor reviews

    2023  Band 74, Seite(n) 56–75

    Abstract: Innate lymphoid cells (ILCs), a growing class of immune cells, imitate the appearance and abilities of T cells. However, unlike T cells, ILCs lack acquired antigen receptors, and they also do not undergo clonal selection or proliferation in response to ... ...

    Abstract Innate lymphoid cells (ILCs), a growing class of immune cells, imitate the appearance and abilities of T cells. However, unlike T cells, ILCs lack acquired antigen receptors, and they also do not undergo clonal selection or proliferation in response to antigenic stimuli. Despite lacking antigen-specific receptors, ILCs respond quickly to signals from infected or damaged tissues and generate an array of cytokines that regulate the development of adaptive immune response. ILCs can be categorized into four types based on their signature cytokines and transcription factors: ILC1, ILC2, ILC3 (including Lymphoid Tissue inducer- LTi cells), and regulatory ILCs (ILCregs). ILCs play key functions in controlling and resolving inflammation, and variations in their proportion are linked to various pathological diseases including cancer, gastrointestinal, pulmonary, and skin diseases. We highlight current advancements in the biology and classification of ILCs in this review. Additionally, we provide a thorough overview of their contributions to several inflammatory bone-related pathologies, including osteoporosis, rheumatoid arthritis, periodontitis, and ankylosing spondylitis. Understanding the multiple functions of ILCs in both physiological and pathological conditions will further mobilize future research towards targeting ILCs for therapeutic purposes.
    Mesh-Begriff(e) Humans ; Lymphocytes ; Immunity, Innate ; Lymphoid Tissue ; Cytokines ; T-Lymphocytes, Helper-Inducer
    Chemische Substanzen Cytokines
    Sprache Englisch
    Erscheinungsdatum 2023-09-16
    Erscheinungsland England
    Dokumenttyp Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 1330534-7
    ISSN 1879-0305 ; 1359-6101
    ISSN (online) 1879-0305
    ISSN 1359-6101
    DOI 10.1016/j.cytogfr.2023.09.002
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