Publications by authors named "Kamarul Tunku"

Despite osteoarthritis (OA) being recognised for over a century as a debilitating disease that affects millions, there are huge gaps in our understanding of the underlying pathophysiology that drives this disease. Present day studies that focussed on ubiquitination (Ub) and ubiquitylation-like (Ubl) modification related mechanisms have brought light into the possibility of attenuating OA development by targeting these specific proteins in chondrocytes. In the present review, we discuss recent advances in studies involving Ub ligases and deubiquitinating enzymes (DUBs) which are of importance in the development of OA, and may offer potential therapeutic strategies for OA.

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Background: Osteoarthritis (OA) is a common degenerative joint disease that poses a significant global healthcare challenge due to its complexity and limited treatment options. Advances in metabolomics have provided insights into OA by identifying dysregulated metabolites and their connection to altered signaling pathways. However, a comprehensive understanding of these biomarkers in OA is still required.

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  • - Endotoxin contamination in MRI contrast agents can lead to immune reactions, raising concerns for patient safety, as there are stricter rules for implants and catheters than for these agents.
  • - The study tested a chromogenic LAL assay to measure endotoxin levels in an MRI contrast agent produced in Malaysia, using water for injection to dissolve the powdered agent.
  • - Results showed a high coefficient of efficiency (≥ 0.98) and endotoxin levels below the safe limit of 0.5 EU/mL, indicating that the contrast agent is unlikely to cause pyrogenic effects.
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Mesenchymal stromal cells (MSCs) have immense potential for use in musculoskeletal tissue regeneration; however, there is still a paucity of evidence on the effect of tenogenic MSCs (TMSCs) in tendon healing . This study aimed to determine the effects of growth differentiation factor 5 (GDF5)-induced rabbit MSCs (rbMSCs) on infraspinatus tendon healing in a New Zealand white rabbit model. In this study, bone marrow-derived rbMSCs were isolated, and 100 ng/mL GDF5 was used to induce tenogenic differentiation in rbMSC.

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Cartilage defects present a significant challenge in orthopedic medicine, often leading to pain and functional impairment. To address this, human amnion, a naturally derived biomaterial, has gained attention for its potential in enhancing cartilage regeneration. This systematic review aims to evaluate the efficacy of human amnion in enhancing cartilage regeneration for full-thickness cartilage defects.

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  • * This study examined how recombinant insulin-like growth factor 1 (rIGF-1) combined with fibrin microbeads (FibIGF1) could enhance cartilage regeneration by promoting better cellular responses.
  • * Results showed that FibIGF1 led to improved quality and integration of cartilage repair in goat knee models, suggesting its potential as an effective clinical option for treating cartilage injuries.
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This study aimed to functionalize a novel porous PLGA (Poly lactic-co-glycolic acid) composite scaffold in combination with nano‑calcium sulphate (nCS) and/or fucoidan (FU) to induce osteogenic differentiation of human bone marrow stromal cells. The composite scaffolds (PLGA-nCS-FU, PLGA-nCS or PLGA-FU) were fabricated and subjected to characterization using Fourier-transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), Scanning electron microscopy (SEM) and Energy Dispersive X-Ray (EDX). The biocompatibility and osteogenic induction potential of scaffolds on seeded human bone marrow derived mesenchymal stromal cells (hBMSCs) were studied using cell attachment and alamar blue cell viability and alkaline phosphatase (ALP), osteocalcin and osteogenic gene expression, respectively.

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Objectives: Diabetes mellitus (DM) is a complex metabolic disease that results from impaired insulin secreting pancreatic β-cells or insulin resistance. Although available medications help control the disease, patients suffer from its complications. Therefore, finding effective therapeutic approaches to treat DM is a priority.

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  • Most research on platelet-rich plasma (PRP) has focused on autologous (self-derived) sources due to concerns about safety and immune rejection with allogenic (donor-derived) sources.
  • Recent advancements have reignited interest in allogenic PRP, showing it to be safe, effective, and plentiful for cartilage repair.
  • A systematic review identified 12 relevant studies, primarily focusing on animal models, which indicated that allogenic PRP can enhance cell proliferation and cartilage repair, despite some conflicting results.
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  • - Osteoarthritis (OA) is the most common chronic joint disease and leads to significant societal costs, but current treatments don't effectively stop or reverse the damage to cartilage, which is crucial in OA progression.
  • - The loss or malfunction of chondrocytes, which are the cells responsible for maintaining cartilage, is a key factor in cartilage breakdown, and their death through a process called apoptosis contributes to this deterioration.
  • - Autophagy, a cell survival mechanism that helps get rid of damaged components, could be a promising treatment target to prevent chondrocyte apoptosis and slow down OA; however, more research is needed to understand how autophagy and apoptosis are connected in these cells.
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Tissue engineering and regenerative medicine (TERM) holds great promise for addressing the growing need for innovative therapies to treat disease conditions. To achieve this, TERM relies on various strategies and techniques. The most prominent strategy is the development of a scaffold.

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  • - Tendon injuries are common and difficult to treat due to slow healing and poor tissue repair, often resulting in weakened, disorganized tissue.
  • - Mesenchymal stem cell (MSC) therapy shows promise for improving tendon repair, especially when MSCs are exposed to low oxygen (hypoxic) conditions, which boosts their ability to differentiate into tendon cells.
  • - The review explores how hypoxia-inducible factor-1-alpha (HIF-1α) is crucial in this process, particularly its interactions with growth factors like FGF-2 and TGF-β1, and highlights strategies to enhance HIF-1α to improve MSC therapy effectiveness.
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In designing porous scaffolds, permeability is essential to consider as a function of cell migration and bone tissue regeneration. Good permeability has been achieved by mimicking the complexity of natural cancellous bone. In this study, a porous scaffold was developed according to the morphological indices of cancellous bone (porosity, specific surface area, thickness, and tortuosity).

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  • The researchers found that both types of MSCs showed similar changes in shape and alignment when stretched, and neither type significantly increased in number.
  • Ultimately, both AD-MSCs and BM-MSCs had comparable levels of collagen and gene expression related to tendon development, indicating that either source could be effective for tendon repair.
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Our previous study evidenced that the 3D CORAGRAF loaded with PLGA microsphere constitutes PDGF-BB can support cell attachment and proliferation and can induce an osteogenic commitment of mesenchymal stromal cells in the in vitro condition. However, how this construct can perform in pathophysiological conditions in terms of repairing critical bone defects is yet to be understood. A study was therefore conducted to investigate the regeneration potential of calvaria critical-size defects using CORAGRAF + PLGA with PDGF-BB + mesenchymal stromal cells (MSCs) in a rat model.

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  • The study examines the relationship between immune cell infiltration in osteoarthritis (OA) synovium and its effects on monocyte activation and migration.
  • Knee-synovium samples from end-stage OA and trauma patients were analyzed, revealing distinct protein profiles and pro-inflammatory markers linked to immune responses in OA.
  • The findings suggest that the unique protein composition of OA synovium leads to significant activation and functional changes in classical monocytes, which may offer insights for therapeutic strategies.
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Transforming growth factor-beta 1 (TGF-β1) has been reported to promote chondrogenic differentiation and proliferation in the multipotent stromal cell (MSCs), and the transforming growth factor-beta 3 (TGF-β3) tends to be exclusively in promoting cell differentiation alone. The objective of this study was to determine the effect of TGF-β1 and -β3 on the MSCs chondrogenic differentiation on the poly (vinyl alcohol)-chitosan-poly (ethylene glycol) (PVA-NOCC-PEG) scaffold, compared with that of monolayer and pellet cultures. In this study, P2 rabbit bone marrow-derived MSCs were seeded either on the untreated six-well plate (for monolayer culture) or onto the PVA-NOCC-PEG scaffold or cultured as a pellet culture.

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The state of host cells is reflected in the cargo carried by their extracellular vesicles (EVs). This makes EV a potential source of biomarkers for human diseases. Piwi-interacting RNA (piRNA) regulates gene expression through epigenetic regulation and post-transcriptional gene silencing.

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Gellan-chitosan (GC) incorporated with CS: 0% (GC-0 CS), 10% (GC-10 CS), 20% (GC-20 CS) or 40% (GC-40 CS) / was prepared using freeze-drying method to investigate its physicochemical, biocompatible, and osteoinductive properties in human bone-marrow mesenchymal stromal cells (hBMSCs). The composition of different groups was reflected in physicochemical analyses performed using BET, FTIR, and XRD. The SEM micrographs revealed excellent hBMSCs attachment in GC-40 CS.

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Microvascular complications are among the major outcomes of patients with type II diabetes mellitus, which are the consequences of impaired physiological functioning of small blood vessels and angiogenic responses in these patients. Overproduction and accumulation of methylglyoxal (MGO), a highly reactive dicarbonyl byproduct of glycolysis pathway, has been acclaimed as the main inducer of impaired angiogenic responses and microvascular dysfunction in diabetic patients with uncontrolled hyperglycemia. Hence, an effective approach to overcome diabetes-associated microvascular complications is to neutralize the deleterious activity of enhanced the concentration of MGO in the body.

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Objectives: Primary Osteoarthritis (OA) is a disease of progressive joints degeneration due to idiopathic causes. Recent evidence showed a positive relationship between OA and metabolic syndrome. This pilot study aimed to assess the baseline level of pro and anti-inflammatory cytokines in OA patients with or without Diabetic Mellitus (DM) and assess the effect of hydrogen peroxide (HO) in cytokine production.

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This work is aimed to develop a biocompatible, bactericidal and mechanically stable biomaterial to overcome the challenges associated with calcium phosphate bioceramics. The influence of chemical composition on synthesis temperature, bioactivity, antibacterial activity and mechanical stability of least explored calcium silicate bioceramics was studied. The current study also investigates the biomedical applications of rankinite (CaSiO) for the first time.

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Background: Cartilage damage, which can potentially lead to osteoarthritis, is a leading cause of morbidity in the elderly population. Chondrocytes are sensitive to mechanical stimuli and their matrix-protein synthesis may be altered when chondrocytes experience a variety of in vivo loadings. Therefore, a study was conducted to evaluate the biosynthesis of isolated osteoarthritic chondrocytes which subjected to compression with varying dynamic compressive strains and loading durations.

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  • The study investigates the role of epithelial sodium channels (ENaC) in the tenogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hMSCs) under mechanical strain.
  • hMSCs were subjected to uniaxial tensile loading, and analyses showed increased expression of tenogenic markers and ENaC subunits during stretching.
  • Blocking ENaC with a specific inhibitor led to a decrease in the expression of these tenogenic markers, indicating that ENaC is crucial for the differentiation of hMSCs in response to mechanical strain.
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Background: Type 2 diabetes mellitus (T2DM) had been reported to be associated with tendinopathy. However, the underlying mechanisms of diabetic tendinopathy still remain largely to be discovered. The purpose of this study was to develop insulin resistance (IR) model on primary human tenocytes (hTeno) culture with tumour necrosis factor-alpha (TNF-α) treatment to study tenocytes homeostasis as an implication for diabetic tendinopathy.

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