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Introduction
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Publications (295)
Spinal cord injury (SCI), caused by significant physical trauma, as well as other pathological conditions, results in electrical signaling disruption and loss of bodily functional control below the injury site. Conductive biomaterials have been considered a promising approach for treating SCI, owing to their ability to restore electrical connection...
It has been documented that the uterus plays a key cardio-protective role in pre-menopausal women, which is supported by uterine cell therapy, to preserve cardiac functioning post-myocardial infarction (MI), being effective among females. However, whether such therapies would also be beneficial among males is still largely unknown. In this study, w...
Background
Heart failure (HF) is a clinical syndrome associated with a progressive decline in myocardial function and low‐grade systemic inflammation. Chronic inflammation can have lasting effects on the bone marrow (BM) stem cell pool by impacting cell renewal and lineage differentiation. However, how HF affects BM stem/progenitor cells remains la...
Myocardial fibrosis, resulting from myocardial infarction (MI), significantly alters cardiac electrophysiological properties. As fibrotic scar tissue forms, its resistance to incoming action potentials increases, leading to cardiac arrhythmia, and eventually sudden cardiac death or heart failure. Biomaterials are gaining increasing attention as an...
[This corrects the article DOI: 10.7150/thno.22788.].
Conical Cardiac Ventricle In article 2101165, Radisic and co‐workers describe a multilayered in vitro model of a cardiac ventricle composed of three layers with different pattern orientations representing the physiological cardiac fiber architecture. This model is fabricated by rolling a 2D elastomeric scaffold seeded with cardiomyocytes around a c...
Conductive polymers have been investigated as a medium for the transmission of electrical signals in biological tissues, but their capacity to rewire cardiac tissue has not been evaluated. Myocardial tissue is unique in being able to generate an electrical potential at a fixed rate; this potential spreads rapidly among cells to trigger muscle contr...
Despite current efforts in organ‐on‐chip engineering to construct miniature cardiac models, they often lack some physiological aspects of the heart, including fiber orientation. This motivates the development of bioartificial left ventricle models that mimic the myofiber orientation of the native ventricle. Herein, an approach relying on microfabri...
Aims
To date, stroke remains one of the leading causes of death and disability worldwide. Nearly three-quarters of all strokes occur in the elderly (>65-years-old), and a vast majority of these individuals develop debilitating cognitive impairments that can later progress into dementia. Currently there are no therapies capable of reversing the cogn...
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Conductive Biopolymers PAMB‐G is a non‐toxic, injectable conductive polymer; it has shown good biocompatibility, as well as long‐term efficacy and stability in alleviating arrhythmia by improving conduction across the fibrotic scar tissue post‐myocardial infarction. This improvement aids in restoring cardiac function and can be found in article num...
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Following myocardial infarction (MI), the resulting fibrotic scar is nonconductive and leads to ventricular dysfunction via electrical uncoupling of the remaining viable cardiomyocytes. The uneven conductive properties between normal myocardium and scar tissue result in arrhythmia, yielding sudden cardiac death/heart failure. A conductive biopolyme...
Ventricular remodeling following myocardial infarction (MI) is a major cause of heart failure, a condition prevalent in older individuals. Following MI, immune cells are mobilized to the myocardium from peripheral lymphoid organs and play an active role in orchestrating repair. While the effect of aging on mouse bone marrow (BM) has been studied, l...
Super-carbon-chain compounds (SCCCs) are marine organic molecules featuring long polyol carbon chains with numerous stereocenters. Polyol-polyene compounds (PPCs) and ladder-frame polyethers (LFPs) are two major families. It is highly challenging to establish the absolute configurations of SCCCs. In this century, few new SCCC families have been rep...
Bone marrow mononuclear cell therapy improves cardiac repair after myocardial infarction (MI), in-part through signaling to resident cardiac cells, such as fibroblasts, which regulate scar formation. The efficacy of cell therapy declines with age, as aging of both donor and recipient cells decreases repair responses. Autophagy regulates the microen...
Optoelectronic biomaterials have recently emerged as a potential treatment option for neurodegenerative diseases, such as optic macular degeneration. Though initial works in the field have involved bulk heterojunctions mimicking solar panels with photovoltaics (PVs) and conductive polymers (CPs), recent developments have considered abandoning CPs i...
Two unprecedented limonoids incorporating a sterically encumbered cyclopropane ring, named granatripodins A (1) and B (2), featuring the presence of a tricyclo[3.3.1.02,8]nonane motif, were obtained from seeds of the Thai Xylocarpus granatum. The planar structures and absolute configurations of these limonoids were unambiguously established by NMR...
Background: Pacemaker implantation is currently used in patients with symptomatic bradycardia. Since a pacemaker is a lifetime therapeutic device, its energy consumption contributes to battery exhaustion, along with its voltage stimulation resulting in local fibrosis and greater resistance, which are all detrimental to patients. The possible resolu...
Seven new limonoids, named krishnolides E–K (1–7), including three khayanolides, two mexicanolides, a derivative of trangmolin A, and an andirobin, were isolated from seeds of the Indian Krishna mangrove, Xylocarpus moluccensis. The structures of these limonoids were established by HRESIMS, extensive NMR investigations, and X-ray crystallography. M...
Recruited immune cells play a critical role in muscle repair, in part by interacting with local stem cell populations to regulate muscle regeneration. How aging affects their communication during myogenesis is unclear. Here, we investigate how aging impacts the cellular function of these two cell types after muscle injury during normal aging or aft...
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Gibbosterol A (1), a water-soluble 14-membered carbocyclic steroid with a twisted trans-9,11-epoxy ring, was discovered from the South China Sea dinoflagellate, Amphidinium gibbosum, together with its acid-induced cyclization product 2. It exhibits marked agonistic effects against human pregnane-X-receptor in a dose-dependent manner within the conc...
A sailboat-shaped 20-membered macrolide, named gibbosolide A, featuring a rare cis-fused 2-methylhexahydro-2H-furo[3,2-b]pyran motif, was obtained from the South China Sea dinoflagellate, Amphidinium gibbosum. Its planar structure and absolute configuration, containing...
Human pregnane–X–receptor (hPXR) is considered to be the key target for the treatment of cholestasis and liver injury. Agonists of hPXR are potential drug leads. Potent and selective inhibitors of human carboxylesterase 2 (hCES2) could be utilized to alleviate the toxicity induced by ester drugs. In this work, fifteen new tetranortriterpenoids with...
A super-carbon-chain compound, named gibbosol C, featuring a polyoxygenated C70-linear-carbon-chain backbone encompassing two acyclic polyol chains, was obtained from the South China Sea dinoflagellate Amphidinium gibbosum. Its planar structure was elucidated by extensive NMR investigations, whereas its absolute configurations, featuring the presen...
TDDFT-ECD calculations were utilized to explain the mirror image or different ECD spectra of previously reported homochiral natural products thaigranatins A–E and granatumin L, the simple comparison of which would result in a wrong stereochemical conclusion. The configurational assignment was confirmed independently and geometrical parameters of th...
Myocardial fibrosis, resulting from ischemic injury, increases tissue resistivity in the infarct area, which impedes heart synchronous electrical propagation. The uneven conduction between myocardium and fibrotic tissue leads to dys-synchronous contraction, which progresses towards ventricular dysfunction. We synthesized a conductive poly-pyrrole-c...
Prevention of infarct scar thinning and dilatation and stimulation of scar contracture can prevent progressive heart failure. Since microRNA 145 (miR‐145) plays an important role in cardiac fibroblast response to wound healing and cardiac repair after an myocardial infarction (MI), using a miR‐145 knock‐out (KO) mouse model, we evaluated contributi...
In this review, the literature data on phytochemical and biological investigations of the genus Ceriops are compiled. The Ceriops species are mangrove plants widely distributed along the sea coasts of Africa, Madagascar, South Asia, and South Pacific islands. To date, 43 diterpenes and 29 triterpenes have been reported from the embryos, fruits, hyp...
Marine dinoflagellates produce remarkable organic molecules, particularly those with polyoxygenated long‐carbon‐chain backbones, namely super‐carbon‐chain compounds (SCCCs), characterized by the presence of numerous stereogenic carbon centers on acyclic polyol carbon chains. Even today, it is a challenge to determine the absolute configurations of...
Super‐carbon‐chain compounds: Gibbosols A and B, obtained from the South China Sea dinoflagellate Amphidinium gibbosum, are stereochemically challenging, flexible super‐carbon‐chain compounds. A combined chemical, spectroscopic, and computational approach was successfully employed to establish the absolute configurations of thirty‐seven stereogenic...
How aging affects the communication between immune cells and myoblasts during myogenesis is unclear. We therefore investigated how aging impacts the cellular synchronization of these two processes after muscle injury. Muscles of old mice (20 months) had chronic inflammation and fewer satellite cells compared to young mice (3 months). After injury,...
Background
Radiotherapy is widely used and effective for treating brain tumours, but inevitably impairs cognition as it arrests cellular processes important for learning and memory. This is particularly evident in the aged brain with limited regenerative capacity, where radiation produces irreparable neuronal damage and activation of neighbouring m...
Cardiac tissue engineering is of particular importance in the combination of contracting cells with a biomaterial scaffold, which serves as a cell-delivery construct, to replace cardiomyocytes (CMs) that are lost as a result of an infarction, to restore heart function. However, most biomaterial scaffolds are nonconductive and may delay regional con...
Following myocardial infarction (MI), necrotic cardiomyocytes (CMs) are replaced by fibroblasts and collagen tissue, causing abnormal electrical signal propagation, desynchronizing cardiac contraction, resulting in cardiac arrhythmia. In this work, a conductive polymer, poly-3-amino-4-methoxybenzoic acid (PAMB), is synthesized and grafted onto non-...
A polyketide-derived alkaloid featuring a unique 3,4-dihydro-2H-indeno[1,2-b]pyridine 1-oxide motif, named phomopsol A (1), and a highly oxidized polyketide containing a new 3,5-dihydro-2H-2,5-methanobenzo[e][1,4]dioxepine moiety, named phomopsol B (2), were isolated from the Thai mangrove endophytic fungus Phomopsis sp. xy21, together with the rel...
A polyketide-derived alkaloid featuring a rotationally hindered C-9-C-9a axial bond and a unique 3,4-dihydro-2 H-indeno[1,2- b]pyridine-1-oxide motif, named phomopsol A (1), and a highly oxidized polyketide containing a new 3,5-dihydro-2 H-2,5-methanobenzo[ e][1,4]dioxepine moiety, named phomopsol B (2), were isolated from the Thai mangrove endophy...
Background:
Cardiac repair depends on angiogenesis and cell proliferation. Previously we identified Canopy 2 (CNPY2) as a secreted angiogenic growth factor which promotes neovascularization. We investigated the role of CNPY2 in cardiac repair following myocardial infarction (MI) and the possible mediators involved using Cnpy2 knockout (KO) mice an...
Five new limonoids named thaigranatins A–E (1–5), containing a C1–O–C29 moiety, were isolated from seeds of the Thai Xylocarpus granatum, collected at the mangrove swamp of Trang Province, together with the known limonoid, granatumin L (6). The structures of these compounds were established by HR-ESIMS and extensive NMR spectroscopic data. The abso...
Retinal ganglion cell apoptosis and optic nerve degeneration are prevalent in aged patients, which may be related to the decrease in bone marrow (BM) stem cell number/function because of the possible cross‐talk between the two organs. This pathological process is accelerated by retinal ischaemia‐reperfusion (I/R) injury. This study investigated whe...
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30-Ketophragmalins are a small group of limonoids. To date, only 21 ones have been exclusively reported from the mangrove, Xylocarpus moluccensis (Lam.) M. Roem. In this paper, three new 30-ketophragmalins, named godavarins L-N (1-3), were obtained from the seeds of X. moluccensis, collected in the mangrove swamp of Godavari estuary, Andhra Pradesh...
Background: The post-myocardial infarction (MI) scar interrupts electrical impulse propagation and delays regional contraction, which contributes to ventricular dysfunction. We investigated the potential of an injectable conductive biomaterial to restore scar tissue conductivity and re-establish synchronous ventricular contraction.
Methods: A condu...
Starting from the natural monomeric limonoids 1 and 1', eight new limonoid dimers of four skeletons (two symmetric and two nonsymmetric), containing a rotationally hindered C15=C15' central axis (2, 2'), an embedded C15-spiro-fused 2H-pyran motif (3, 3'), and an axially chiral C15–C15' central bond (4, 4', and 5a, 5b), respectively, were designed a...
Background: To improve the regenerative capacity of aged individuals, we reconstituted bone marrow (BM) of aged mice with young Sca-1 cells, which repopulated cardiac progenitors and prevented cardiac dysfunction after a myocardial infarction (MI). However, the mechanisms involved were incompletely elucidated. This study aimed to investigate whethe...
A convenient protocol for highly selective delivery of azoxybenzenes from reduction of nitrobenzenes was developed by utilizing a copper catalyst. A variety of functional groups and substitution were well tolerated.
Tagalide A (1) and tagalol A (2), representing dolabrane-type diterpenes with unprecedented ring-A/B/C/D- and ring-A/B/C-fused cores (vii-viii), respectively, were isolated from the Chinese mangrove, Ceriops tagal. The relative and absolute configurations of these dolabranes were unambiguously established by HRESIMS, extensive NMR investigations, a...
Background:
Both stable and biodegradable biomaterials have been used to surgically repair congenital cardiac defects. However, neither type of biomaterial can conduct electrical activity. We evaluated the conductivity and efficacy of a newly synthesized conductive polypyrrole-chitosan (Ppy+Chi) gelfoam patch to support cardiomyocyte (CM) viabilit...
Reduced regenerative capacity of aged stem cells hampers the benefits of autologous cell therapy for cardiac regeneration. This study investigated whether neuron-derived neurotrophic factor (NDNF) could rejuvenate aged human bone marrow (hBM)- multipotent mesenchymal stromal cells (MSCs) and whether the rejuvenated hBM-MSCs could improve cardiac re...
Despite great progress in engineering functional tissues for organ repair, including the heart, an invasive surgical approach is still required for their implantation. Here, we designed an elastic and microfabricated scaffold using a biodegradable polymer (poly(octamethylene maleate (anhydride) citrate)) for functional tissue delivery via injection...
Five new limonoids, named sundarbanxylogranins A-E (1-5), were isolated from the seeds of an Indian mangrove, Xylocarpus granatum, collected from mangrove swamps of the Sundarbans, India. The structures of these limonoids were established by HRESIMS and NMR spectroscopic data. Sundarbanxylogranin A (1) is a rare limonoid containing a bicyclo[5.2.1]...
Recruitment of stem cells from the bone marrow (BM) is an important aspect of cardiac healing that becomes inefficient with age. We investigated the role of young stem cell antigen 1 (Sca-1)-positive BM cells on the aged heart by microarray analysis after BM reconstitution. Sca-1(+) and Sca-1(-) BM cells from young green fluorescent protein (GFP)-p...
Bone marrow (BM) reconstitution with young BM cells in aged recipients restores the functionality of cardiac resident BM-derived progenitors. This study investigated the cell type primarily responsible for this effect. We reconstituted old mice with BM cells from young or old mice and found that the number of stem cell antigen 1 (Sca-1) cells homin...
Ischemic cardiac injury is the main contributor to heart failure, and the regenerative capacity of intrinsic stem cells plays an important role in tissue repair after injury. However, stem cells in aged individuals have reduced regenerative potential and aged tissues lack the capacity to renew. Growth differentiation factor 11 (GDF11), from the act...
From the twigs and stems of the Chinese liana Ancistrocladus tectorius (Ancistrocladaceae), two new 5,8′-coupled naphthylisoquinolines, ancistectorine D (5) and its 6-O-demethyl derivative 6, were isolated, along with two new 7,1′-linked alkaloids, 6-O-methylancistectorine B1 (7) and ancistectorine B2 (8). Two further compounds, ancistroealaine A (...
Background:
Revascularization of the heart after myocardial infarction (MI) using growth factors delivered by hydrogel-based microspheres represents a promising therapeutic approach for cardiac regeneration. Microspheres have tuneable degradation properties and support the prolonged release of soluble factors. Cardiac patches provide mechanical re...
Two novel phragmalin 8,9,12-orthoesters, named thaixylomolins O-P (1-2), a 9,10-seco mexicanolide with a unique trans-orientation of H5 and Me-19, named thaixylomolin Q (3), and the first secomahoganin-type 7-nor-limonoid with a 6-oxabicyclo[3.2.1]octan-3-one motif, named thaixylomolin R (4), were isolated from the seeds of a Thai mangrove, Xylocar...
Ischemic heart disease is the leading cause of mortality in industrialized countries. Cell transplantation could restore function of the ischemic heart likely through the mechanism of cell-induced angiogenesis. We have previously shown that cells isolated from uteri increase angiogenesis and alleviate cardiac dysfunction when transplanted after MI....
Human gene therapy has made significant advances in less than two decades. Within this short period of time, gene therapy has proceeded from the conceptual stage to technology development and laboratory research, and finally to clinical trials for the treatment of a variety of deadly diseases. Cardiovascular disease, cancer, and stroke are leading...
From the leaves and stems of Ancistrocladus tectorius (Ancistrocladaceae) from the Chinese island Hainan, two novel-Type 7,3'-coupled naphthylisoquinolines, named ancistrotectoquinones A (4) and B (5), were isolated. They are the first alkaloids with a 1,4-naphthoquinone portion coupled to an isoquinoline moiety. Due to the lowered degree of steric...
Neovascularization drives tumor development, and angiogenic factors are important neovascularization initiators. We recently identified the secreted angiogenic factor CNPY2, but its involvement in cancer has not been explored. Herein, we investigate CNPY2's role in human colorectal cancer (CRC) development. Tumor samples were obtained from CRC pati...
Purpose:
We generated a folate-conjugated porphyrin nanoparticle (porphysome) suitable for multimodal non-invasive active macrophage tracking post-myocardial infarction (MI).
Procedures:
Macrophage uptake of folate-conjugated porphysomes was selective. Folate-porphysome cardiac macrophage tracking was detected in vivo using radioligand and fluor...
Background:
Autologous bone marrow mesenchymal stem cell (BM-MSC) transplantation is a novel strategy for treating ischemic heart disease. However, limited benefits have been reported in aging patients. Rejuvenation of aged human BM-MSCs could be a means to improve the efficacy of stem cell transplantation in older patients. While it has been show...
Introduction: During myocardial infarction (MI) the ischemic heart muscle loses a substantial number of cells, and a poorly vascularised fibrotic scar forms. We previously showed that local injections of first trimester human umbilical cord perivascular cells (FTM-HUCPVCs) diminish scar tissue and significantly improve cardiac output after MI in ra...
Introduction: We previously reported that bone marrow (BM) reconstitution with young BM cells into aged recipients restored progenitors in both the BM and the myocardium and improved functional recovery post-injury. Here, our goal was to identify the specific cell type responsible for the improved cardiac regeneration and to restore that capacity i...
Introduction: Scar formation after a myocardial infarction (MI) delays electrical impulse propagation, inducing dysynchronous cardiac activation and uncoordinated contraction. We generated an injectable biocompatible conductive polymer that not only stabilized the infarct region, but also facilitated electrical signal propagation across the scar ti...
Introduction: The benefits of cell transplantation for cardiac repair are diminished in aged individuals and effective methods to rejuvenate aged stem cells are required to treat the increasing number of elderly patients with heart failure. Neuron-derived neurotrophic factor (NDNF) has biological effects which could restore stem cell activity. This...
A new tirucallane, 3β-hydroxy-3-decarbonyl-24-epi-piscidinol A (1), and two new pairs of tetranortriterpene 23-epimers, named thaimoluccepimers A (2) and B (3), were isolated from the seeds of a Thai mangrove, Xylocarpus moluccensis. The structures of these compounds were elucidated by HRESIMS and NMR spectroscopic analysis.
Efficient cardiac function requires synchronous ventricular contraction. After myocardial infarction, the nonconductive nature of scar tissue contributes to ventricular dysfunction by electrically uncoupling viable cardiomyocytes in the infarct region. Injection of a conductive biomaterial polymer that restores impulse propagation could synchronize...
A mismatch between adequate angiogenesis and overgrowth of myocytes may be a critical mechanism controlling the transition from adaptive hypertrophy to heart failure. Canopy 2 (CNPY2) was recently identified as a secreted, HIF-1α-regulated angiogenic growth factor. As angiogenic factors play important roles in the development of myocardial hypertro...
Eight new khayanolides, named thaixylomolins G-N (1-8), two new phragmalins (9 and 10), and two new mexicanolides (11 and 12) were obtained from the seeds of the Trang mangrove plant Xylocarpus moluccensis. The absolute configurations of these limonoids, except for the stereocenter at C-6 of 11 and 12, were assigned by experimental and TDDFT calcul...
To understand the molecular pathways underlying the cardiac preconditioning effect of short-term caloric restriction (CR).
Lifelong CR has been suggested to reduce the incidence of cardiovascular disease through a variety of mechanisms. However, prolonged adherence to a CR life-style is difficult. Here we reveal the pathways that are modulated by s...
To investigate the secondary metabolites of endophytic fungi Peeicinia sp. F-31. Column chromatography on silica gel Sephadex LH-20 and semi-preparative HPLC were used to separate and purify the compounds. Two compounds were isolated from the fermentation broth of Peeiyonia sp. Their structures were identified as 5-( 1-hydroxyhexyl) -6 - methyl-2H-...
Interleukin-10 (IL-10) gene transduction into allogeneic smooth muscle cells (SMCs) was evaluated to improve the long-term benefits of allogeneic cell transplantation into infarcted myocardium. Allogeneic cells, including SMCs, have been demonstrated to restore cardiac function and repair the infarcted myocardium, but late rejection of the transpla...
Cell therapy to prevent cardiac dysfunction after myocardial infarction (MI) is less effective in aged patients because aged cells have decreased regenerative capacity. Allogeneic transplanted stem cells (SCs) from young donors are usually rejected. Maintaining transplanted SC immunoprivilege may dramatically improve regenerative outcomes. The uter...
