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Fulltext Extracellular Vesicles from Mesenchymal Stem Cells as Potential Treatments for Osteoarthritis

Mohd Noor NA, Abdullah Nurul A, Ahmad Mohd Zain MR, Wan Nor Aduni WK, Azlan M

Cells, 2021 05 22;10(6).
PMID: 34067325 DOI: 10.3390/cells10061287

Osteoarthritis (OA) is a chronic degenerative disorder of the joint and its prevalence and severity is increasing owing to ageing of the population. Osteoarthritis is characterized by the degradation of articular cartilage and remodeling of the underlying bone. There is little understanding of the cellular and molecular processes involved in pathophysiology of OA. Currently the treatment for OA is limited to painkillers and anti-inflammatory drugs, which only treat the symptoms. Some patients may also undergo surgical procedures to replace the damaged joints. Extracellular vesicles (EV) play an important role in intercellular communications and their concentration is elevated in the joints of OA patients, although their mechanism is unclear. Extracellular vesicles are naturally released by cells and they carry their origin cell information to be delivered to target cells. On the other hand, mesenchymal stem cells (MSCs) are highly proliferative and have a great potential in cartilage regeneration. In this review, we provide an overview of the current OA treatments and their limitations. We also discuss the role of EV in OA pathophysiology. Finally, we highlight the therapeutic potential of MSC-derived EV in OA and their challenges.
Fulltext Cytotoxic and radiosensitising effects of a novel thioredoxin reductase inhibitor in breast cancer

Abdullah NA, Inman M, Moody CJ, Storr SJ, Martin SG

Invest New Drugs, 2021 10;39(5):1232-1241.
PMID: 33768386 DOI: 10.1007/s10637-021-01106-5

Radiotherapy is an effective treatment modality for breast cancer but, unfortunately, not all patients respond fully with a significant number experiencing local recurrences. Overexpression of thioredoxin and thioredoxin reductase has been reported to cause multidrug and radiation resistance - their inhibition may therefore improve therapeutic efficacy. Novel indolequinone compounds have been shown, in pancreatic cancer models, to inhibit thioredoxin reductase activity and exhibit potent anticancer activity. The present study evaluates, using in vitro breast cancer models, the efficacy of a novel indolequinone compound (IQ9) as a single agent and in combination with ionising radiation using a variety of endpoint assays including cell proliferation, clonogenic survival, enzyme activity, and western blotting. Three triple-negative breast cancer (MDA-MB-231, MDA-MB-468, and MDA-MB-436) and two luminal (MCF-7 and T47D) breast cancer cell lines were used. Results show that treatment with IQ9 significantly inhibited thioredoxin reductase activity, and inhibited cell growth and colony formation of breast cancer cells with IC50 values in the low micromolar ranges. Enhanced radiosensitivity of triple-negative breast cancer cells was observed, with sensitiser enhancement ratios of 1.20-1.43, but with no evident radiosensitisation of luminal breast cancer cell lines. IQ9 upregulated protein expression of thioredoxin reductase in luminal but not in triple-negative breast cancer cells which may explain the observed differential radiosensitisation. This study provides important evidence of the roles of the thioredoxin system as an exploitable radiobiological target in breast cancer cells and highlights the potential therapeutic value of indolequinones as radiosensitisers.***This study was not part of a clinical trial. Clinical trial registration number: N/A.
Fulltext Analysis of serum and gene expression profile of cytokines (IL-6, TNF-α and TGF-β1) in chronic hepatitis C virus infection

Che Noh I, Avoi R, Abdullah Nurul A, Ahmad I, Abu Bakar R

PeerJ, 2022;10:e13330.
PMID: 35469194 DOI: 10.7717/peerj.13330

BACKGROUND: Chronic hepatitis C virus (HCV) infection is one of the major causes of liver cirrhosis and liver carcinoma. Studies have indicated that an imbalance of cytokine activities could contribute to the pathogenesis of chronic HCV infection. This study aimed to investigate serum levels and gene expression of cytokines (IL-6, TNF-α and TGF-β1) in chronic HCV infection among Malay male subjects.
METHODS: Thirty-nine subjects were enrolled from various health clinics in Kelantan, Malaysia, and divided into two groups: patients with chronic HCV infection (HP) and healthy control (HS). The serum cytokines IL-6, TNF-a-were measured using Luminex assay, and serum TGF-β1 was measured by ELISA. The mRNA gene expression for IL-6, TNF-α and TGF-β1 was measured by real-time reverse transcriptase polymerase chain reaction (RT-PCR).
RESULTS: There were statistically significant differences in the mean serum levels of IL-6, and TGF-β1 in HP compared to HS group (p = 0.0180 and p = 0.0005, respectively). There was no significant difference in the mean serum level of TNF-α in HP compared to HS group. The gene expression for the studied cytokines showed no significant differences in HP compared to HS group.
CONCLUSION: Serum IL-6 was significantly associated with chronic HCV infection.
Fulltext COVID-19 screening test by using random oropharyngeal saliva

Rao M, Rashid FA, Sabri FSAH, Jamil NN, Seradja V, Abdullah NA, et al.

J Med Virol, 2021 Apr;93(4):2461-2466.
PMID: 33393672 DOI: 10.1002/jmv.26773

An optimal clinical specimen for accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by minimizing the usage of consumables and reduce hazard exposure to healthcare workers is an urgent priority. The diagnostic performance of SARS-CoV-2 detection between healthcare worker-collected nasopharyngeal and oropharyngeal (NP + OP) swabs and patient performed self-collected random saliva was assessed. Paired NP + OP swabs and random saliva were collected and processed within 48 h of specimen collection from two cohort studies which recruited 562 asymptomatic adult candidates. Real-time reverse-transcription polymerase chain reaction targeting Open reading frame 1a (ORF1a) and nucleocapsid (N) genes was performed and the results were compared. Overall, 65 of 562 (28.1%) candidates tested positive for COVID-19 based on random saliva, NP + OP swabs, or both testing techniques. The detection rate of SARS-CoV-2 was higher in random saliva compared to NP + OP testing (92.3%; 60/65 vs. 73.8%; 48/65; p