Displaying publications 1 - 20 of 45 in total

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  1. sFRP-mediated Wnt sequestration as a potential therapeutic target for Alzheimer's disease
    Warrier S, Marimuthu R, Sekhar S, Bhuvanalakshmi G, Arfuso F, Das AK, et al.
    Int J Biochem Cell Biol, 2016 06;75:104-11.
    PMID: 27063405 DOI: 10.1016/j.biocel.2016.04.002
    The extracellular ligand, Wnt, and its receptors are involved in sign al transduction and play an important role in axis formation and neural development. In neurodegenerative disorders such as Alzheimer's disease (AD), a decrease of the intracellular Wnt effector, β-catenin, has been linked to amyloid-β-peptide-induced neurotoxicity. Despite this knowledge, targeting Wnt inhibitors as potential biomarkers has not been explored, and harnessing Wnt activators as therapeutic candidates remains largely not investigated. A wide acting family of Wnt mediators, secreted frizzled-related proteins (sFRPs), has not been probed so far as molecular indicators of disease occurrence and progression of Alzheimer's. Unlike the effect of the Dickkopf (DKK) family of Wnt antagonists on AD, the sFRP molecules have a more pleiotropic impact on the Wnt signaling cascade and probably have a far-reaching involvement in neurodegeneration. The role of sFRPs has been poorly described in AD, and in this review, we analyze the present status of the role of sFRPs on neurodegeneration, their likely involvement, and potential implications in treatment modalities of AD. This information would provide valuable clues for the development of potential therapeutic targets for aberrant neurodegenerative disorders.
  2. Understanding the multifaceted mechanisms of diabetic wound healing and therapeutic application of stem cells conditioned medium in the healing process
    Fui LW, Lok MPW, Govindasamy V, Yong TK, Lek TK, Das AK
    J Tissue Eng Regen Med, 2019 12;13(12):2218-2233.
    PMID: 31648415 DOI: 10.1002/term.2966
    Mesenchymal stem cells (MSCs) transplantation seems to be a promising new therapy for diabetic wound healing (DWH), and currently, arrays of MSCs from various sources ranging from umbilical, adipose to dental sources are available as a treatment modality for this disease. However, it now appears that only a fraction of transplanted cells actually assimilate and survive in host tissues suggesting that the major mechanism by which stem cells participate in tissue repair are most likely related to their secretome level. These include a wide range of growth factors, cytokines, and chemokines, which can be found from the conditioned medium (CM) used to culture the cells. Basic studies and preclinical work confirm that the therapeutic effect of CMs are comparable with the application of stem cells. This review describes in detail the wound healing process in diabetes and the cellular and biological factors that influence the process. Subsequently, through a comprehensive literature search of studies related to wound healing in diabetics, we aim to provide an overview of scientific merits of using MSCs-CM in the treatment of diabetic wound as well as the significant caveats, which restricts its potential use in clinical set-ups. To our best knowledge, this is one of the first review papers that collect the importance of stem cells as an alternative treatment to the DWH. We anticipate that the success of this treatment will have a significant clinical impact on diabetic wounds.
  3. Fulltext Transplantation of human bone marrow mesenchymal stromal cells reduces liver fibrosis more effectively than Wharton's jelly mesenchymal stromal cells
    Rengasamy M, Singh G, Fakharuzi NA, Siddikuzzaman, Balasubramanian S, Swamynathan P, et al.
    Stem Cell Res Ther, 2017 06 13;8(1):143.
    PMID: 28610623 DOI: 10.1186/s13287-017-0595-1
    BACKGROUND: Mesenchymal stromal cells (MSCs) from various tissues have shown moderate therapeutic efficacy in reversing liver fibrosis in preclinical models. Here, we compared the relative therapeutic potential of pooled, adult human bone marrow (BM)- and neonatal Wharton's jelly (WJ)-derived MSCs to treat CCl4-induced liver fibrosis in rats.

    METHODS: Sprague-Dawley rats were injected with CCl4 for 8 weeks to induce irreversible liver fibrosis. Ex-vivo expanded, pooled human MSCs obtained from BM and WJ were intravenously administered into rats with liver fibrosis at a dose of 10 × 106 cells/animal. Sham control and vehicle-treated animals served as negative and disease controls, respectively. The animals were sacrificed at 30 and 70 days after cell transplantation and hepatic-hydroxyproline content, histopathological, and immunohistochemical analyses were performed.

    RESULTS: BM-MSCs treatment showed a marked reduction in liver fibrosis as determined by Masson's trichrome and Sirius red staining as compared to those treated with the vehicle. Furthermore, hepatic-hydroxyproline content and percentage collagen proportionate area were found to be significantly lower in the BM-MSCs-treated group. In contrast, WJ-MSCs treatment showed less reduction of fibrosis at both time points. Immunohistochemical analysis of BM-MSCs-treated liver samples showed a reduction in α-SMA+ myofibroblasts and increased number of EpCAM+ hepatic progenitor cells, along with Ki-67+ and human matrix metalloprotease-1+ (MMP-1+) cells as compared to WJ-MSCs-treated rat livers.

    CONCLUSIONS: Our findings suggest that BM-MSCs are more effective than WJ-MSCs in treating liver fibrosis in a CCl4-induced model in rats. The superior therapeutic activity of BM-MSCs may be attributed to their expression of certain MMPs and angiogenic factors.

  4. Fulltext The ethics of penal amputation
    Das AK
    Indian J Med Ethics, 2020 5 13;V(2):143-148.
    PMID: 32393455 DOI: 10.20529/IJME.2020.032
    Malaysia is a South East Asian country with a racially diverse population. Islam is the state religion and about 60% of the population is Muslim, but the rights of other religious groups are protected by law. The Parti Islam se Malaysia, which has ruled the state of Kelantan since 1999, and believes that Malaysia should be ruled by Sharia law, recently proposed the implementation of Hudud laws in Kelantan. However, the federal government has ruled out its implementation. The suggestion stirred up a controversy among the physician community and the Malaysian Medical Association rejected a proposal by the state's political leadership to utilise the services of qualified surgeons to carry out punitive limb amputations. Several Islamic states such as Sudan, Saudi Arabia, and Iran practice Islamic penal justice, including amputations. The question therefore arises: how should a modern medical practitioner approach this ethical question? This study focuses mainly on Malaysia, but draws upon practices in other Islamic countries also.
  5. Fulltext The current landscape of the mesenchymal stromal cell secretome: A new paradigm for cell-free regeneration
    Konala VB, Mamidi MK, Bhonde R, Das AK, Pochampally R, Pal R
    Cytotherapy, 2016 Jan;18(1):13-24.
    PMID: 26631828 DOI: 10.1016/j.jcyt.2015.10.008
    The unique properties of mesenchymal stromal/stem cells (MSCs) to self-renew and their multipotentiality have rendered them attractive to researchers and clinicians. In addition to the differentiation potential, the broad repertoire of secreted trophic factors (cytokines) exhibiting diverse functions such as immunomodulation, anti-inflammatory activity, angiogenesis and anti-apoptotic, commonly referred to as the MSC secretome, has gained immense attention in the past few years. There is enough evidence to show that the one important pathway by which MSCs participate in tissue repair and regeneration is through its secretome. Concurrently, a large body of MSC research has focused on characterization of the MSC secretome; this includes both soluble factors and factors released in extracellular vesicles, for example, exosomes and microvesicles. This review provides an overview of our current understanding of the MSC secretome with respect to their potential clinical applications.
  6. Fulltext The Ethics of the Reuse of Disposable Medical Supplies
    Das AK, Okita T, Enzo A, Asai A
    Asian Bioeth Rev, 2020 Jun;12(2):103-116.
    PMID: 33717332 DOI: 10.1007/s41649-020-00114-6
    The use of single-use items (SUDs) is now ubiquitous in medical practice. Because of the high costs of these items, the practice of reusing them after sterilisation is also widespread especially in resource-poor economies. However, the ethics of reusing disposable items remain unclear. There are several analogous conditions, which could shed light on the ethics of reuse of disposables. These include the use of restored kidney transplantation and the use of generic drugs etc. The ethical issues include the question of patient safety and the possibility of infection. It is also important to understand the role (or otherwise) of informed consent before reuse of disposables. The widespread practice of reuse may bring down high healthcare costs and also reduce the huge amount of hospital waste that is generated. The reuse of disposables can be justified on various grounds including the safety and the cost effectiveness of this practice.
  7. Stem cells in stroke repair: current success and future prospects
    Gopurappilly R, Pal R, Mamidi MK, Dey S, Bhonde R, Das AK
    CNS Neurol Disord Drug Targets, 2011 Sep 1;10(6):741-56.
    PMID: 21838668
    Stroke causes a devastating insult to the brain resulting in severe neurological deficits because of a massive loss of different neurons and glia. In the United States, stroke is the third leading cause of death. Stroke remains a significant clinical unmet condition, with only 3% of the ischemic patient population benefiting from current treatment modalities, such as the use of thrombolytic agents, which are often limited by a narrow therapeutic time window. However, regeneration of the brain after ischemic damage is still active days and even weeks after stroke occurs, which might provide a second window for treatment. Neurorestorative processes like neurogenesis, angiogenesis and synaptic plasticity lead to functional improvement after stroke. Stem cells derived from various tissues have the potential to perform all of the aforementioned processes, thus facilitating functional recovery. Indeed, transplantation of stem cells or their derivatives in animal models of cerebral ischemia can improve function by replacing the lost neurons and glial cells and by mediating remyelination, and modulation of inflammation as confirmed by various studies worldwide. While initially stem cells seemed to work by a 'cell replacement' mechanism, recent research suggests that cell therapy works mostly by providing trophic support to the injured tissue and brain, fostering both neurogenesis and angiogenesis. Moreover, ongoing human trials have encouraged hopes for this new method of restorative therapy after stroke. This review describes up-to-date progress in cell-based therapy for the treatment of stroke. Further, as we discuss here, significant hurdles remain to be addressed before these findings can be responsibly translated to novel therapies. In particular, we need a better understanding of the mechanisms of action of stem cells after transplantation, the therapeutic time window for cell transplantation, the optimal route of cell delivery to the ischemic brain, the most suitable cell types and sources and learn how to control stem cell proliferation, survival, migration, and differentiation in the pathological environment. An integrated approach of cell-based therapy with early-phase clinical trials and continued preclinical work with focus on mechanisms of action is needed.
  8. Fulltext Stem cell therapy for critical limb ischaemia - a review
    Das AK
    Indian J Surg, 2009 Aug;71(4):177-81.
    PMID: 23133150 DOI: 10.1007/s12262-009-0059-7
    Critical limb ischaemia is an intractable condition associated with high levels of amputation, leading to a low quality of life and increased morbidity and mortality. It is often not treatable by standard therapeutic modalities. Neoangiogenesis has been proposed as a novel method of treatment of such patients. Vascular endothelial growth factor (VEGF) and cytokine fibroblast growth factor (FGF-1) have been shown to elicit neoangiogenesis. Stem cells are progenitor cells which can differentiate in vivo into different types of cells. Mesenchymal stem cells (MSCs) are a type of adult stem cells which have an immunomodulatory effect. Stem cell therapy has been used in animal studies to improve limb vascularity in rat and rabbit models. Several clinical studies have also validated their use for critical limb ischaemia. However many issues are still unresolved. These include the dosage, delivery and safety issues in relation to stem cell therapy. However stem cells are likely to be an important therapeutic modality to treat critical limb ischaemia in the near future.
  9. Search for Scalar Leptoquarks Produced via τ-Lepton-Quark Scattering in pp Collisions at sqrt[s]=13  TeV
    Hayrapetyan A, Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, et al.
    Phys Rev Lett, 2024 Feb 09;132(6):061801.
    PMID: 38394587 DOI: 10.1103/PhysRevLett.132.061801
    The first search for scalar leptoquarks produced in τ-lepton-quark collisions is presented. It is based on a set of proton-proton collision data recorded with the CMS detector at the LHC at a center-of-mass energy of 13 TeV corresponding to an integrated luminosity of 138  fb^{-1}. The reconstructed final state consists of a jet, significant missing transverse momentum, and a τ lepton reconstructed through its hadronic or leptonic decays. Limits are set on the product of the leptoquark production cross section and branching fraction and interpreted as exclusions in the plane of the leptoquark mass and the leptoquark-τ-quark coupling strength.
  10. Search for Nonresonant Pair Production of Highly Energetic Higgs Bosons Decaying to Bottom Quarks
    Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, Damanakis K, et al.
    Phys Rev Lett, 2023 Jul 28;131(4):041803.
    PMID: 37566864 DOI: 10.1103/PhysRevLett.131.041803
    A search for nonresonant Higgs boson (H) pair production via gluon and vector boson (V) fusion is performed in the four-bottom-quark final state, using proton-proton collision data at 13 TeV corresponding to 138  fb^{-1} collected by the CMS experiment at the LHC. The analysis targets Lorentz-boosted H pairs identified using a graph neural network. It constrains the strengths relative to the standard model of the H self-coupling and the quartic VVHH couplings, κ_{2V}, excluding κ_{2V}=0 for the first time, with a significance of 6.3 standard deviations when other H couplings are fixed to their standard model values.
  11. Search for Inelastic Dark Matter in Events with Two Displaced Muons and Missing Transverse Momentum in Proton-Proton Collisions at sqrt[s]=13  TeV
    Hayrapetyan A, Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, et al.
    Phys Rev Lett, 2024 Jan 26;132(4):041802.
    PMID: 38335361 DOI: 10.1103/PhysRevLett.132.041802
    A search for dark matter in events with a displaced nonresonant muon pair and missing transverse momentum is presented. The analysis is performed using an integrated luminosity of 138  fb^{-1} of proton-proton (pp) collision data at a center-of-mass energy of 13 TeV produced by the LHC in 2016-2018. No significant excess over the predicted backgrounds is observed. Upper limits are set on the product of the inelastic dark matter production cross section σ(pp→A^{'}→χ_{1}χ_{2}) and the decay branching fraction B(χ_{2}→χ_{1}μ^{+}μ^{-}), where A^{'} is a dark photon and χ_{1} and χ_{2} are states in the dark sector with near mass degeneracy. This is the first dedicated collider search for inelastic dark matter.
  12. Search for Higgs Boson and Observation of Z Boson through Their Decay into a Charm Quark-Antiquark Pair in Boosted Topologies in Proton-Proton Collisions at sqrt[s]=13  TeV
    Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, Damanakis K, et al.
    Phys Rev Lett, 2023 Jul 28;131(4):041801.
    PMID: 37566854 DOI: 10.1103/PhysRevLett.131.041801
    A search for the standard model (SM) Higgs boson (H) produced with transverse momentum (p_{T}) greater than 450 GeV and decaying to a charm quark-antiquark (cc[over ¯]) pair is presented. The search is performed using proton-proton collision data collected at sqrt[s]=13  TeV by the CMS experiment at the LHC, corresponding to an integrated luminosity of 138  fb^{-1}. Boosted H→cc[over ¯] decay products are reconstructed as a single large-radius jet and identified using a deep neural network charm tagging technique. The method is validated by measuring the Z→cc[over ¯] decay process, which is observed in association with jets at high p_{T} for the first time with a signal strength of 1.00_{-0.14}^{+0.17}(syst)±0.08(theo)±0.06(stat), defined as the ratio of the observed process rate to the SM expectation. The observed (expected) upper limit on σ(H)B(H→cc[over ¯]) is set at 47 (39) times the SM prediction at 95% confidence level.
  13. Search for Higgs Boson Decay to a Charm Quark-Antiquark Pair in Proton-Proton Collisions at sqrt[s]=13  TeV
    Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, Damanakis K, et al.
    Phys Rev Lett, 2023 Aug 11;131(6):061801.
    PMID: 37625071 DOI: 10.1103/PhysRevLett.131.061801
    A search for the standard model Higgs boson decaying to a charm quark-antiquark pair, H→cc[over ¯], produced in association with a leptonically decaying V (W or Z) boson is presented. The search is performed with proton-proton collisions at sqrt[s]=13  TeV collected by the CMS experiment, corresponding to an integrated luminosity of 138  fb^{-1}. Novel charm jet identification and analysis methods using machine learning techniques are employed. The analysis is validated by searching for Z→cc[over ¯] in VZ events, leading to its first observation at a hadron collider with a significance of 5.7 standard deviations. The observed (expected) upper limit on σ(VH)B(H→cc[over ¯]) is 0.94 (0.50_{-0.15}^{+0.22})pb at 95% confidence level (C.L.), corresponding to 14 (7.6_{-2.3}^{+3.4}) times the standard model prediction. For the Higgs-charm Yukawa coupling modifier, κ_{c}, the observed (expected) 95% C.L. interval is 1.1
  14. Search for Exotic Higgs Boson Decays H→AA→4γ with Events Containing Two Merged Diphotons in Proton-Proton Collisions at sqrt[s]=13  TeV
    Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, Damanakis K, et al.
    Phys Rev Lett, 2023 Sep 08;131(10):101801.
    PMID: 37739361 DOI: 10.1103/PhysRevLett.131.101801
    We present the first direct search for exotic Higgs boson decays H→AA, A→γγ in events with two photonlike objects. The hypothetical particle A is a low-mass spin-0 particle decaying promptly to a merged diphoton reconstructed as a single photonlike object. We analyze the data collected by the CMS experiment at sqrt[s]=13  TeV corresponding to an integrated luminosity of 136  fb^{-1}. No excess above the estimated background is found. We set upper limits on the branching fraction B(H→AA→4γ) of (0.9-3.3)×10^{-3} at 95% confidence level for masses of A in the range 0.1-1.2 GeV.
  15. Fulltext Response to Commentary by Adriaan van Es
    Das AK
    Indian J Med Ethics, 2020 5 13;V(2):151.
    PMID: 32393445 DOI: 10.20529/IJME.2020.043
    I would like to thank Dr Adriaan Van Es for his commentary (1) on my article (2). To start with, let me make one thing clear: I am not sure why he thinks that I am condoning the practice of penal amputation. As I clearly state in my conclusion, the arguments that may (or may not) justify penal amputation are abhorrent in liberal societies. We are on the same side here. But what of those who live in less secular societies where religious faith may be unquestioned? In my opinion, van Es has resorted to a typical example of a tortured form of ethical logic (3), which researchers from countries that have different value systems and different problems have deplored, albeit in a different context.
  16. Fulltext Randomised clinical trials in surgery: a look at the ethical and practical issues
    Das AK
    Indian J Surg, 2011 Aug;73(4):245-50.
    PMID: 22851835 DOI: 10.1007/s12262-011-0307-5
    An ethically conducted randomised controlled trial (RCT) is the backbone of evidence based medicine. In surgical practice however, RCTs have taken a backseat, drawing much adverse comment. There are several reasons to explain surgeons' disinclination to conduct RCTs. These include many practical difficulties such as the problem of blinding surgical procedures, design and funding issues. There are also many ethical issues which need to be considered including the concept of equipoise as well as the ethical issues associated with sham surgery as a control. While there is no doubt that RCTs are essential and in fact have helped to weed out several unnecessary surgical procedures, it is important not to lose sight of the fact that they may not be always necessary in order to obtain evidence in favour of a procedure. Possible solutions could be to follow guidelines that have been issued by learned bodies and a strict adherence to all ethical norms that have been recommended in the conduct of trials.
  17. Probing Small Bjorken-x Nuclear Gluonic Structure via Coherent J/ψ Photoproduction in Ultraperipheral Pb-Pb Collisions at sqrt[s_{NN}]=5.02  TeV
    Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, Damanakis K, et al.
    Phys Rev Lett, 2023 Dec 29;131(26):262301.
    PMID: 38215362 DOI: 10.1103/PhysRevLett.131.262301
    Quasireal photons exchanged in relativistic heavy ion interactions are powerful probes of the gluonic structure of nuclei. The coherent J/ψ photoproduction cross section in ultraperipheral lead-lead collisions is measured as a function of photon-nucleus center-of-mass energies per nucleon (W_{γN}^{Pb}) over a wide range of 40
  18. Probing Heavy Majorana Neutrinos and the Weinberg Operator through Vector Boson Fusion Processes in Proton-Proton Collisions at sqrt[s]=13  TeV
    Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, Damanakis K, et al.
    Phys Rev Lett, 2023 Jul 07;131(1):011803.
    PMID: 37478454 DOI: 10.1103/PhysRevLett.131.011803
    The first search exploiting the vector boson fusion process to probe heavy Majorana neutrinos and the Weinberg operator at the LHC is presented. The search is performed in the same-sign dimuon final state using a proton-proton collision dataset recorded at sqrt[s]=13  TeV, collected with the CMS detector and corresponding to a total integrated luminosity of 138  fb^{-1}. The results are found to agree with the predictions of the standard model. For heavy Majorana neutrinos, constraints on the squared mixing element between the muon and the heavy neutrino are derived in the heavy neutrino mass range 50 GeV-25 TeV; for masses above 650 GeV these are the most stringent constraints from searches at the LHC to date. A first test of the Weinberg operator at colliders provides an observed upper limit at 95% confidence level on the effective μμ Majorana neutrino mass of 10.8 GeV.
  19. Observation of τ Lepton Pair Production in Ultraperipheral Pb-Pb Collisions at sqrt[s_{NN}]=5.02  TeV
    Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, Damanakis K, et al.
    Phys Rev Lett, 2023 Oct 13;131(15):151803.
    PMID: 37897747 DOI: 10.1103/PhysRevLett.131.151803
    We present an observation of photon-photon production of τ lepton pairs in ultraperipheral lead-lead collisions. The measurement is based on a data sample with an integrated luminosity of 404  μb^{-1} collected by the CMS experiment at a center-of-mass energy per nucleon pair of sqrt[s_{NN}]=5.02  TeV. The γγ→τ^{+}τ^{-} process is observed for τ^{+}τ^{-} events with a muon and three charged hadrons in the final state. The measured fiducial cross section is σ(γγ→τ^{+}τ^{-})=4.8±0.6(stat)±0.5(syst)  μb, where the second (third) term corresponds to the statistical (systematic) uncertainty in σ(γγ→τ^{+}τ^{-}) in agreement with leading-order QED predictions. Using σ(γγ→τ^{+}τ^{-}), we estimate a model-dependent value of the anomalous magnetic moment of the τ lepton of a_{τ}=0.001_{-0.089}^{+0.055}.
  20. Observation of the Rare Decay of the η Meson to Four Muons
    Hayrapetyan A, Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, et al.
    Phys Rev Lett, 2023 Sep 01;131(9):091903.
    PMID: 37721839 DOI: 10.1103/PhysRevLett.131.091903
    A search for the rare η→μ^{+}μ^{-}μ^{+}μ^{-} double-Dalitz decay is performed using a sample of proton-proton collisions, collected by the CMS experiment at the CERN LHC with high-rate muon triggers during 2017 and 2018 and corresponding to an integrated luminosity of 101  fb^{-1}. A signal having a statistical significance well in excess of 5 standard deviations is observed. Using the η→μ^{+}μ^{-} decay as normalization, the branching fraction B(η→μ^{+}μ^{-}μ^{+}μ^{-})=[5.0±0.8(stat)±0.7(syst)±0.7(B_{2μ})]×10^{-9} is measured, where the last term is the uncertainty in the normalization channel branching fraction. This work achieves an improved precision of over 5 orders of magnitude compared to previous results, leading to the first measurement of this branching fraction, which is found to agree with theoretical predictions.
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