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Fulltext Mesenchymal Stem Cells: Current Concepts in the Management of Inflammation in Osteoarthritis

Nurul AA, Azlan M, Ahmad Mohd Zain MR, Sebastian AA, Fan YZ, Fauzi MB

Biomedicines, 2021 Jul 07;9(7).
PMID: 34356849 DOI: 10.3390/biomedicines9070785

Osteoarthritis (OA) has traditionally been known as a "wear and tear" disease, which is mainly characterized by the degradation of articular cartilage and changes in the subchondral bone. Despite the fact that OA is often thought of as a degenerative disease, the catabolic products of the cartilage matrix often promote inflammation by activating immune cells. Current OA treatment focuses on symptomatic treatment, with a primary focus on pain management, which does not promote cartilage regeneration or attenuate joint inflammation. Since articular cartilage have no ability to regenerate, thus regeneration of the tissue is one of the key targets of modern treatments for OA. Cell-based therapies are among the new therapeutic strategies for OA. Mesenchymal stem cells (MSCs) have been extensively researched as potential therapeutic agents in cell-based therapy of OA due to their ability to differentiate into chondrocytes and their immunomodulatory properties that can facilitate cartilage repair and regeneration. In this review, we emphasized current knowledge and future perspectives on the use of MSCs by targeting their regeneration potential and immunomodulatory effects in the treatment of OA.
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.
Role of MicroRNAs in Inflammatory Joint Diseases: A Review

Syed NH, Mussa A, Elmi AH, Jamal Al-Khreisat M, Ahmad Mohd Zain MR, Nurul AA

Immunol Invest, 2024 Feb;53(2):185-209.
PMID: 38095847 DOI: 10.1080/08820139.2023.2293095

Inflammatory arthritis commonly initiates in the soft tissues lining the joint. This lining swells, as do the cells in it and inside the joint fluid, producing chemicals that induce inflammation signs such as heat, redness, and swelling. MicroRNA (miRNA), a subset of non-coding small RNA molecules, post-transcriptionally controls gene expression by targeting their messenger RNA. MiRNAs modulate approximately 1/3 of the human genome with their multiple targets. Recently, they have been extensively studied as key modulators of the innate and adaptive immune systems in diseases such as allergic disorders, types of cancer, and cardiovascular diseases. However, research on the different inflammatory joint diseases, such as rheumatoid arthritis, gout, Lyme disease, ankylosing spondylitis, and psoriatic arthritis, remains in its infancy. This review presents a deeper understanding of miRNA biogenesis and the functions of miRNAs in modulating the immune and inflammatory responses in the above-mentioned inflammatory joint diseases. According to the literature, it has been demonstrated that the development of inflammatory joint disorders is closely related to different miRNAs and their specific regulatory mechanisms. Furthermore, they may present as possible prognostic and diagnostic biomarkers for all diseases and may help in developing a therapeutic response. However, further studies are needed to determine whether manipulating miRNAs can influence the development and progression of inflammatory joint disorders.
Exosomes in Osteoarthritis: A Review on Their Isolation Techniques and Therapeutic Potential

Syed NH, Misbah I, Azlan M, Ahmad Mohd Zain MR, Nurul AA

Indian J Orthop, 2024 Jul;58(7):866-875.
PMID: 38948378 DOI: 10.1007/s43465-024-01175-7

BACKGROUND: Exosomes are the smallest extracellular vesicles (30-150 nm) secreted by all cell types, including synovial fluid. However, because biological fluids are complex, heterogeneous, and contain contaminants, their isolation is difficult and time-consuming. Furthermore, the pathophysiology of osteoarthritis (OA) involves exosomes carrying complex components that cause macrophages to release chemokines and proinflammatory cytokines. This narrative review aims to provide in-depth insights into exosome biology, isolation techniques, role in OA pathophysiology, and potential role in future OA therapeutics.
METHODS: A literature search was conducted using PubMed, Scopus, and Web of Science databases for studies involving exosomes in the osteoarthritis using keywords "Exosomes" and "Osteoarthritis". Relevant articles in the last 15 years involving both human and animal models were included. Studies involving exosomes in other inflammatory diseases were excluded.
RESULTS: Despite some progress, conventional techniques for isolating exosomes remain laborious and difficult, requiring intricate and time-consuming procedures across various body fluids and sample origins. Moreover, exosomes are involved in various physiological processes associated with OA, like cartilage calcification, degradation of osteoarthritic joints, and inflammation.
CONCLUSION: The process of achieving standardization, integration, and high throughput of exosome isolation equipment is challenging and time-consuming. The integration of various methodologies can be employed to effectively address specific issues by leveraging their complementary benefits. Exosomes have the potential to effectively repair damaged cartilage OA, reduce inflammation, and maintain a balance between the formation and breakdown of cartilage matrix, therefore showing promise as a therapeutic option for OA.
Biogenic silver nanoparticles (AgNPs) from Tinosporacordifolia leaves: An effective antibiofilm agent against Staphylococcus aureus ATCC 23235

Ghosh S, Mondol S, Lahiri D, Nag M, Sarkar T, Pati S, et al.

Front Chem, 2023;11:1118454.
PMID: 36959877 DOI: 10.3389/fchem.2023.1118454

Medicinal plants are long known for their therapeutic applications. Tinospora cordifolia (commonly called gulancha or heart-leaved moonseed plant), a herbaceous creeper widely has been found to have antimicrobial, anti-inflammatory, anti-diabetic, and anti-cancer properties. However, there remains a dearth of reports regarding its antibiofilm activities. In the present study, the anti-biofilm activities of phytoextractof T. cordifolia and the silver nanoparticles made from this phytoextract were tested against the biofilm of S.taphylococcus aureus, one of the major nosocomial infection-producing bacteria taking tetracycline antibiotic as control. Both phytoextract from the leaves of T. cordifolia, and the biogenic AgNPs from the leaf extract of T. cordifolia, were found successful in reducing the biofilm of Staphylococcus aureus. The biogenic AgNPs formed were characterized by UV- Vis spectroscopy, Field emission Scanning Electron Microscopy (FE- SEM), and Dynamic light scattering (DLS) technique. FE- SEM images showed that the AgNPs were of size ranging between 30 and 50 nm and were stable in nature, as depicted by the zeta potential analyzer. MIC values for phytoextract and AgNPs were found to be 180 mg/mL and 150 μg/mL against S. aureusrespectively. The antibiofilm properties of the AgNPs and phytoextract were analyzed using the CV assay and MTT assay for determining the reduction of biofilms. Reduction in viability count and revival of the S. aureus ATCC 23235 biofilm cells were analyzed followed by the enfeeblement of the EPS matrix to quantify the reduction in the contents of carbohydrates, proteins and eDNA. The SEM analyses clearly indicated that although the phytoextracts could destroy the biofilm network of S. aureuscells yet the biogenicallysynthesizedAgNPs were more effective in biofilm disruption. Fourier Transformed Infrared Radiations (FT- IR) analyses revealed that the AgNPs could bring about more exopolysaccharide (EPS) destruction in comparison to the phytoextract. The antibiofilm activities of AgNPs made from the phytoextract were found to be much more effective than the non-conjugated phytoextract, indicating the future prospect of using such particles for combatting biofilm-mediated infections caused by S aureus.
Fulltext LC-TOF-MS/MS and GC-MS based phytochemical profiling and evaluation of wound healing activity of Oroxylum Indicum (L.) Kurz (Beka)

Abdulhafiz F, Reduan MFH, Hisam AH, Mohammad I, Abdul Wahab IR, Abdul Hamid FF, et al.

Front Pharmacol, 2022;13:1050453.
PMID: 36483735 DOI: 10.3389/fphar.2022.1050453

Background: Beka (Oroxylum indicum (L.) Kurz) has been used as a culinary herb and natural remedy by the local communities in Malaysia. The leaf of O. indicum is traditionally used for the treatment of diarrhea, high blood pressure, and improving digestive health. Objectives: The present study was conducted to evaluate the phytochemical constituents and wound healing properties (in vitro and in vivo models) of aqueous and ethanol extracts of O. indicum leaves. Methods: The total phenolic (TPC) and total flavonoid (TFC) contents in the plant extracts were determined by the spectrophotometric methods. Further, the extract was characterized by Liquid Chromatography Time-of-Flight Mass Spectrometry (LC-TOF-MS/MS) and Gas Chromatography-Mass Spectrometry (GC-MS). The wound healing activity was assessed using the in vitro scratch wound-healing assay and in vivo excisional wound model. Results: The results show the ethanol leaves extract had the higher TPC (164 mg GAE/g) when compared with the aqueous leaves extract (30 mg gallic acid equivalents/g). The ethanol leaves extract was also found to have higher TFC (101 mg Catechin equivalents/g) than the aqueous leaves extract (76 mg Catechin equivalents/g). The ethanol leaves extract was then used for further chemical analysis. The LC-TOF-MS/MS analysis showed that the leaves extracts of O. indicum contains many important compounds such as Orientin, Chrysin, Pinoquercetin, Cupressuflavone, Puerarin xyloside, Forsythiaside and Paederoside. In GC-MS analysis, 19 compounds were identified in ethanolic leaves extract. The wound healing studies shows that O. indicum has promising wound healing activity by increasing the rate of wound contraction significantly (p < 0.05). Conclusion: In conclusion, the present study showed that O. indicum leaf contains important phytochemicals and the wound healing potential of the O. indicum extract may probably be as a result of the presence of various phytoconstituents.
Fulltext Bioactivity and Pharmacological Potential of Date Palm (Phoenix dactylifera L.) Against Pandemic COVID-19: a Comprehensive Review

Ahmad Mohd Zain MR, Abdul Kari Z, Dawood MAO, Nik Ahmad Ariff NS, Salmuna ZN, Ismail N, et al.

Appl Biochem Biotechnol, 2022 Oct;194(10):4587-4624.
PMID: 35579740 DOI: 10.1007/s12010-022-03952-2

A novel coronavirus disease (COVID-19) or severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), transmitted from person to person, has quickly emerged as the pandemic responsible for the current global health crisis. This infection has been declared a global pandemic, resulting in a concerning number of deaths as well as complications post-infection, primarily among vulnerable groups particularly older people and those with multiple comorbidities. In this article, we review the most recent research on the role of date palm (Phoenix dactylifera L.) fruits (DPFs) to prevent or treat COVID-19 infection. The mechanisms underlying this preventive or therapeutic effect are also discussed in terms of bioactivity potentials in date palm, e.g., antimicrobial, antioxidant, anticancer, anti-diabetic, anti-inflammatory, neuroprotective, and hemolytic potential, as well as prospect against COVID-19 disease and the potential product development. Therefore, it can be concluded that regular consumption of DPFs may be associated with a lower risk of some chronic diseases. Indeed, DPFs have been widely used in folk medicine since ancient times to treat a variety of health conditions, demonstrating the importance of DPFs as a nutraceutical and source of functional nourishment. This comprehensive review aims to summarize the majority of the research on DPFs in terms of nutrient content and biologically active components such as phenolic compounds, with an emphasis on their roles in improving overall health as well as the potential product development to ensure consumers' satisfaction in a current pandemic situation. In conclusion, DPFs can be given to COVID-19 patients as a safe and effective add-on medication or supplement in addition to routine treatments.