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  1. Fulltext Orthosiphon stamineus Proteins Alleviate Pentylenetetrazol-Induced Seizures in Zebrafish
    Chung YS, Choo BKM, Ahmed PK, Othman I, Shaikh MF
    Biomedicines, 2020 Jul 02;8(7).
    PMID: 32630817 DOI: 10.3390/biomedicines8070191
    The anticonvulsive potential of proteins extracted from Orthosiphon stamineus leaves (OSLP) has never been elucidated in zebrafish (Danio rerio). This study thus aims to elucidate the anticonvulsive potential of OSLP in pentylenetetrazol (PTZ)-induced seizure model. Physical changes (seizure score and seizure onset time, behavior, locomotor) and neurotransmitter analysis were elucidated to assess the pharmacological activity. The protective mechanism of OSLP on brain was also studied using mass spectrometry-based label-free proteomic quantification (LFQ) and bioinformatics. OSLP was found to be safe up to 800 µg/kg and pre-treatment with OSLP (800 µg/kg, i.p., 30 min) decreased the frequency of convulsive activities (lower seizure score and prolonged seizure onset time), improved locomotor behaviors (reduced erratic swimming movements and bottom-dwelling habit), and lowered the excitatory neurotransmitter (glutamate). Pre-treatment with OSLP increased protein Complexin 2 (Cplx 2) expression in the zebrafish brain. Cplx2 is an important regulator in the trans-SNARE complex which is required during the vesicle priming phase in the calcium-dependent synaptic vesicle exocytosis. Findings in this study collectively suggests that OSLP could be regulating the release of neurotransmitters via calcium-dependent synaptic vesicle exocytosis mediated by the "Synaptic Vesicle Cycle" pathway. OSLP's anticonvulsive actions could be acting differently from diazepam (DZP) and with that, it might not produce the similar cognitive insults such as DZP.
  2. 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.
  3. Fulltext Injectable Hydrogels for Chronic Skin Wound Management: A Concise Review
    Zawani M, Fauzi MB
    Biomedicines, 2021 May 10;9(5).
    PMID: 34068490 DOI: 10.3390/biomedicines9050527
    Diabetic foot ulcers (DFU) are a predominant impediment among diabetic patients, increasing morbidity and wound care costs. There are various strategies including using biomaterials have been explored for the management of DFU. This paper will review the injectable hydrogel application as the most studied polymer-based hydrogel based on published journals and articles. The main key factors that will be discussed in chronic wounds focusing on diabetic ulcers include the socioeconomic burden of chronic wounds, biomaterials implicated by the government for DFU management, commercial hydrogel product, mechanism of injectable hydrogel, the current study of novel injectable hydrogel and the future perspectives of injectable hydrogel for the management of DFU.
  4. Fulltext Type II Collagen-Conjugated Mesenchymal Stem Cells Micromass for Articular Tissue Targeting
    Sulaiman SB, Chowdhury SR, Busra MFBM, Abdul Rani RB, Mohamad Yahaya NHB, Tabata Y, et al.
    Biomedicines, 2021 Jul 23;9(8).
    PMID: 34440084 DOI: 10.3390/biomedicines9080880
    The tissue engineering approach in osteoarthritic cell therapy often requires the delivery of a substantially high cell number due to the low engraftment efficiency as a result of low affinity binding of implanted cells to the targeted tissue. A modification towards the cell membrane that provides specific epitope for antibody binding to a target tissue may be a plausible solution to increase engraftment. In this study, we intercalated palmitated protein G (PPG) with mesenchymal stem cells (MSCs) and antibody, and evaluated their effects on the properties of MSCs either in monolayer state or in a 3D culture state (gelatin microsphere, GM). Bone marrow MSCs were intercalated with PPG (PPG-MSCs), followed by coating with type II collagen antibody (PPG-MSC-Ab). The effect of PPG and antibody conjugation on the MSC proliferation and multilineage differentiation capabilities both in monolayer and GM cultures was evaluated. PPG did not affect MSC proliferation and differentiation either in monolayer or 3D culture. The PPG-MSCs were successfully conjugated with the type II collagen antibody. Both PPG-MSCs with and without antibody conjugation did not alter MSC proliferation, stemness, and the collagen, aggrecan, and sGAG expression profiles. Assessment of the osteochondral defect explant revealed that the PPG-MSC-Ab micromass was able to attach within 48 h onto the osteochondral surface. Antibody-conjugated MSCs in GM culture is a potential method for targeted delivery of MSCs in future therapy of cartilage defects and osteoarthritis.
  5. Fulltext WIN55,212-2 Attenuates Cognitive Impairments in AlCl3 + d-Galactose-Induced Alzheimer's Disease Rats by Enhancing Neurogenesis and Reversing Oxidative Stress
    Mahdi O, Chiroma SM, Hidayat Baharuldin MT, Mohd Nor NH, Mat Taib CN, Jagadeesan S, et al.
    Biomedicines, 2021 Sep 19;9(9).
    PMID: 34572456 DOI: 10.3390/biomedicines9091270
    Neurotransmission and cognitive dysfunctions have been linked to old age disorders including Alzheimer's disease (AD). Aluminium is a known neurotoxic metal, whereas d-galactose (d-gal) has been established as a senescence agent. WIN55,212-2 (WIN), is a potent cannabinoid agonist which partially restores neurogenesis in aged rats. The current study aimed to explore the therapeutic potentials of WIN on Aluminium chloride (AlCl3) and d-gal-induced rat models with cognitive dysfunction. Healthy male albino Wistar rats weighing between 200-250 g were injected with d-gal 60 mg/kg intra peritoneally (i.p), while AlCl3 (200 mg/kg) was orally administered once daily for 10 consecutive weeks. Subsequently, from weeks 8-11 rats were co-administered with WIN (0.5, 1 and 2 mg/kg/day) and donepezil 1 mg/kg. The cognitive functions of the rats were assessed with a Morris water maze (MWM). Furthermore, oxidative stress biomarkers; malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and neurogenesis markers: Nestin and glial fibrillary acidic protein (GFAP) were also evaluated, as well as the histology of the hippocampus. The results revealed that rats exposed to AlCl3 and d-gal alone showed cognitive impairments and marked neuronal loss (p < 0.05) in their hippocampal conus ammonis 1 (CA1). Additionally, a significant decrease in the expressions of GFAP and Nestin was also observed, including increased levels of MDA and decreased levels of SOD and GSH. However, administration of WIN irrespective of the doses given reversed the cognitive impairments and the associated biochemical derangements. As there were increases in the levels SOD, GSH, Nestin and GFAP (p < 0.05), while a significant decrease in the levels of MDA was observed, besides attenuation of the aberrant cytoarchitecture of the rat's hippocampi. The biochemical profiles of the WIN-treated rats were normal. Thus, these findings offer possible scientific evidence of WIN being an effective candidate in the treatment of AD-related cognitive deficits.
  6. Fulltext Stem Cells and Cancer Stem Cells: The Jekyll and Hyde Scenario and Their Implications in Stem Cell Therapy
    Wan Kamarul Zaman WS, Nurul AA, Nordin F
    Biomedicines, 2021 Sep 17;9(9).
    PMID: 34572431 DOI: 10.3390/biomedicines9091245
    "Jekyll and Hyde" refers to persons with an unpredictably dual personality, who are battling between good and evil within themselves In this regard, even cells consist of good and evil counterparts. Normal stem cells (NSCs) and cancer stem cells (CSCs) are two types of cells that share some similar characteristics but have distinct functions that play a major role in physiological and pathophysiological development. In reality, NSCs such as the adult and embryonic stem cells, are the good cells and the ultimate treatment used in cell therapy. CSCs are the corrupted cells that are a subpopulation of cancer cells within the cancer microenvironment that grow into a massive tumour or malignancy that needs to be treated. Hence, understanding the connection between NSCs and CSCs is important not just in cancer development but also in their therapeutic implication, which is the focus of this review.
  7. Fulltext Cytokine (IL-10, IL-6, TNF-α and TGF-β1) Gene Polymorphisms in Chronic Hepatitis C Virus Infection among Malay Male Drug Abusers
    Noh IC, Ahmad I, Suraiya S, Musa NF, Nurul AA, Ruzilawati AB
    Biomedicines, 2021 Aug 30;9(9).
    PMID: 34572300 DOI: 10.3390/biomedicines9091115
    Cytokines play an important role in modulating inflammation during viral infection, including hepatitis C virus (HCV) infection. Genetic polymorphisms of cytokines can alter the immune response against this infection. The objective of this study was to investigate the possible association between chronic hepatitis C virus infection susceptibility and cytokine gene polymorphism for interleukin-10 (IL-10) rs1800896 and rs1800871, interleukin 6 (IL-6) rs1800795, TNF-α rs1800629, and TGF-β1 rs1800471 in Malay male drug abusers. The study was conducted on 76 HCV-positive (HP) male drug abusers and 40 controls (HCV-negative male drug abusers). We found that there were significant differences in the frequencies of genotype for IL-10 rs1800871 (p = 0.0386) and at the allelic level for IL-10 rs1800896 A versus G allele (p = 0.0142) between the HP group and the control group. However, there were no significant differences in gene polymorphism in interleukin 6 rs1800795, TNF-α rs1800629 and TGF-β1 rs1800471. These findings suggest significant associations between gene polymorphism for IL-10 rs1800871, IL-10 rs1800896 (at the allelic level) and susceptibility to HCV infection among Malay male drug abusers.
  8. Fulltext Neuroprotective and Anti-Inflammatory Effects of Rhus coriaria Extract in a Mouse Model of Ischemic Optic Neuropathy
    Khalilpour S, Behnammanesh G, Suede F, Ezzat MO, Muniandy J, Tabana Y, et al.
    Biomedicines, 2018 Apr 23;6(2).
    PMID: 29690612 DOI: 10.3390/biomedicines6020048
    Modulating oxidative stresses and inflammation can potentially prevent or alleviate the pathological conditions of diseases associated with the nervous system, including ischemic optic neuropathy. In this study we evaluated the anti-neuroinflammatory and neuroprotective activities of Rhus coriaria (R. coriaria) extract in vivo. The half maximal inhibitory concentration (IC50) for DPPH, ABTS and β⁻carotene were 6.79 ± 0.009 µg/mL, 10.94 ± 0.09 µg/mL, and 6.25 ± 0.06 µg/mL, respectively. Retinal ischemia was induced by optic nerve crush injury in albino Balb/c mice. The anti-inflammatory activity of ethanolic extract of R. coriaria (ERC) and linoleic acid (LA) on ocular ischemia was monitored using Fluorescence Molecular Tomography (FMT). Following optic nerve crush injury, the mice treated with 400 mg/kg of ERC and LA exhibited an 84.87% and 86.71% reduction of fluorescent signal (cathepsin activity) respectively. The results of this study provide strong scientific evidence for the neuroprotective activity of the ERC, identifying LA as one of the main components responsible for the effect. ERC may be useful and worthy of further development for its adjunctive utilization in the treatment of optic neuropathy.
  9. Fulltext Footprints of microRNAs in Cancer Biology
    Rajasegaran Y, Azlan A, Rosli AA, Yik MY, Kang Zi K, Yusoff NM, et al.
    Biomedicines, 2021 Oct 19;9(10).
    PMID: 34680611 DOI: 10.3390/biomedicines9101494
    MicroRNAs (miRNAs) are short non-coding RNAs involved in post-transcriptional gene regulation. Over the past years, various studies have demonstrated the role of aberrant miRNA expression in the onset of cancer. The mechanisms by which miRNA exerts its cancer-promoting or inhibitory effects are apparent through the various cancer hallmarks, which include selective proliferative advantage, altered stress response, vascularization, invasion and metastasis, metabolic rewiring, the tumor microenvironment and immune modulation; therefore, this review aims to highlight the association between miRNAs and the various cancer hallmarks by dissecting the mechanisms of miRNA regulation in each hallmark separately. It is hoped that the information presented herein will provide further insights regarding the role of cancer and serve as a guideline to evaluate the potential of microRNAs to be utilized as biomarkers and therapeutic targets on a larger scale in cancer research.
  10. Fulltext The Role of Epigenetics in the Development and Progression of Multiple Myeloma
    Ismail NH, Mussa A, Zakaria NA, Al-Khreisat MJ, Zahidin MA, Ramli NN, et al.
    Biomedicines, 2022 Oct 31;10(11).
    PMID: 36359286 DOI: 10.3390/biomedicines10112767
    Multiple myeloma (MM) is an exceptionally complicated and heterogeneous disease that is caused by the abnormal proliferation of malignant monoclonal plasma cells initiated in the bone marrow. In disease progression, a multistep process including differentiation, proliferation, and invasion is involved. Despite great improvement in treatment outcomes in recent years due to the substantial discovery of novel therapeutic drugs, MM is still regarded as an incurable disease. Patients with MM are afflicted by confronting remission periods accompanied by relapse or progression outcomes, which inevitably progress to the refractory stage. In this regard, MM may need new medications or modifications in therapeutic strategies to overcome resistance. A variety of genetic abnormalities (e.g., point mutations, translocations, and deletions) and epigenetic changes (e.g., DNA methylation, histone modification, and non-coding RNA) contribute to the pathogenesis and development of MM. Here, we review the significant roles of epigenetic mechanisms in the development and progression of MM. We also highlight epigenetic pathways as potential novel treatment avenues for MM, including their interplay, use of epigenetic inhibitors, and major involvement in immuno-oncology.
  11. Fulltext Immune Checkpoint Molecules and Glucose Metabolism in HIV-Induced T Cell Exhaustion
    Chan YT, Cheong HC, Tang TF, Rajasuriar R, Cheng KK, Looi CY, et al.
    Biomedicines, 2022 Nov 04;10(11).
    PMID: 36359329 DOI: 10.3390/biomedicines10112809
    The progressive decline of CD8+ cytotoxic T cells in human immunodeficiency virus (HIV)-infected patients due to infection-triggered cell exhaustion and cell death is significantly correlated with disease severity and progression into the life-threatening acquired immunodeficiency syndrome (AIDS) stage. T cell exhaustion is a condition of cell dysfunction despite antigen engagement, characterized by augmented surface expression of immune checkpoint molecules such as programmed cell death protein 1 (PD-1), which suppress T cell receptor (TCR) signaling and negatively impact the proliferative and effector activities of T cells. T cell function is tightly modulated by cellular glucose metabolism, which produces adequate energy to support a robust reaction when battling pathogen infection. The transition of the T cells from an active to an exhausted state following pathogen persistence involves a drastic change in metabolic activity. This review highlights the interplay between immune checkpoint molecules and glucose metabolism that contributes to T cell exhaustion in the context of chronic HIV infection, which could deliver an insight into the rational design of a novel therapeutic strategy.
  12. Fulltext Subchondral Bone Microarchitectural and Mineral Properties and Expression of Key Degradative Proteinases by Chondrocytes in Human Hip Osteoarthritis
    Li Y, Liem Y, Zamli Z, Sullivan N, Dall'Ara E, Ahmed H, et al.
    Biomedicines, 2021 Nov 01;9(11).
    PMID: 34829822 DOI: 10.3390/biomedicines9111593
    BACKGROUND: The purpose of this study was to investigate the relationship between the expression of key degradative enzymes by chondrocytes and the microarchitectural and mineral properties of subchondral bone across different stages of cartilage degradation in human hip osteoarthritis (OA).

    METHODS: Osteochondral samples at different stages of cartilage degradation were collected from 16 femoral heads with OA. Osteochondral samples with normal cartilage were collected from seven femoral heads with osteoporosis. Microcomputed tomography was used for the investigation of subchondral bone microarchitecture and mineral densities. Immunohistochemistry was used to study the expression and distribution of MMP13 and ADAMTS4 in cartilage.

    RESULTS: The microarchitecture and mineral properties of the subchondral plate and trabecular bone in OA varied with the severity of the degradation of the overlying cartilage. Chondrocytes expressing MMP13 and ADAMTS4 are mainly located in the upper zone(s) of cartilage regardless of the histopathological grades. The zonal expression of these enzymes in OA (i.e., the percentage of positive cells in the superficial, middle, and deep zones), rather than their overall expression (the percentage of positive cells in the full thickness of the cartilage), exhibited significant variation in relation to the severity of cartilage degradation. The associations between the subchondral bone properties and zonal and overall expression of these enzymes in the cartilage were generally weak or nonsignificant.

    CONCLUSIONS: Phenotypic changes in chondrocytes and remodelling of subchondral bone proceed at different rates throughout the process of cartilage degradation. Biological influences are more important for cartilage degradation at early stages, while biomechanical damage to the compromised tissue may outrun the phenotypic change of chondrocytes and is critical in the advanced stages.

  13. Fulltext Adipose-Derived Stem Cell: "Treat or Trick"
    Airuddin SS, Halim AS, Wan Sulaiman WA, Kadir R, Nasir NAM
    Biomedicines, 2021 Nov 05;9(11).
    PMID: 34829853 DOI: 10.3390/biomedicines9111624
    Stem cells have been widely used for treating disease due to the various benefits they offer in the curing process. Several treatments using stem cells have undergone clinical trials, such as cell-based therapies for heart disease, sickle cell disease, thalassemia, etc. Adipose-derived stem cells are some of the many mesenchymal stem cells that exist in our body that can be harvested from the abdomen, thighs, etc. Adipose tissue is easy to harvest, and its stem cells can be obtained in higher volumes compared to stem cells harvested from bone marrow, for which a more invasive technique is required with a smaller volume obtained. Many scientists have expressed interest in investigating the role of adipose-derived stem cells in treating disease since their use was first described. This is due to these stem cells' ability to differentiate into multiple lineages and secrete a variety of growth factors and proteins. Previous studies have found that the hormones, cytokines, and growth factors contained in adipose tissue play major roles in the metabolic regulation of adipose tissue, as well as in energy balance and whole-body homeostasis through their endocrine, autocrine, and paracrine functions. These are thought to be important contributors to the process of tissue repair and regeneration. However, it remains unclear how effective and safe ADSCs are in treating diseases. The research that has been carried out to date is in order to investigate the impact of ADSCs in disease treatment, as described in this review, to highlight its "trick or treat" effect in medical treatment.
  14. Novel Nematode-Killing Protein-1 (Nkp-1) from a Marine Epiphytic Bacterium Pseudoalteromonas tunicata
    Salikin NH, Dubois M, Nappi J, Lebhar H, Marquis C, Egan S
    Biomedicines, 2021 Oct 30;9(11).
    PMID: 34829814 DOI: 10.3390/biomedicines9111586
    Drug resistance among parasitic nematodes has resulted in an urgent need for the development of new therapies. However, the high re-discovery rate of anti-nematode compounds from terrestrial environments necessitates a new repository for future drug research. Marine epiphytes are hypothesised to produce nematicidal compounds as a defence against bacterivorous predators, thus representing a promising yet underexplored source for anti-nematode drug discovery. The marine epiphytic bacterium Pseudoalteromonas tunicata is known to produce several bioactive compounds. Screening heterologously expressed genomic libraries of P. tunicata against the nematode Caenorhabditis elegans, identified as an E. coli clone (HG8), shows fast-killing activity. Here we show that clone HG8 produces a novel nematode-killing protein-1 (Nkp-1) harbouring a predicted carbohydrate-binding domain with weak homology to known bacterial pore-forming toxins. We found bacteria expressing Nkp-1 were able to colonise the C. elegans intestine, with exposure to both live bacteria and protein extracts resulting in physical damage and necrosis, leading to nematode death within 24 h of exposure. Furthermore, this study revealed C. elegans dar (deformed anal region) and internal hatching may act as a nematode defence strategy against Nkp-1 toxicity. The characterisation of this novel protein and putative mode of action not only contributes to the development of novel anti-nematode applications in the future but reaffirms the potential of marine epiphytic bacteria as a new source of novel biomolecules.
  15. Fulltext Potential of Marine Terpenoids against SARS-CoV-2: An In Silico Drug Development Approach
    Sahoo A, Fuloria S, Swain SS, Panda SK, Sekar M, Subramaniyan V, et al.
    Biomedicines, 2021 Oct 20;9(11).
    PMID: 34829734 DOI: 10.3390/biomedicines9111505
    In an emergency, drug repurposing is the best alternative option against newly emerged severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, several bioactive natural products have shown potential against SARS-CoV-2 in recent studies. The present study selected sixty-eight broad-spectrum antiviral marine terpenoids and performed molecular docking against two novel SARS-CoV-2 enzymes (main protease or Mpro or 3CLpro) and RNA-dependent RNA polymerase (RdRp). In addition, the present study analysed the physiochemical-toxicity-pharmacokinetic profile, structural activity relationship, and phylogenetic tree with various computational tools to select the 'lead' candidate. The genomic diversity study with multiple sequence analyses and phylogenetic tree confirmed that the newly emerged SARS-CoV-2 strain was up to 96% structurally similar to existing CoV-strains. Furthermore, the anti-SARS-CoV-2 potency based on a protein-ligand docking score (kcal/mol) exposed that the marine terpenoid brevione F (-8.4) and stachyflin (-8.4) exhibited similar activity with the reference antiviral drugs lopinavir (-8.4) and darunavir (-7.5) against the target SARS-CoV-Mpro. Similarly, marine terpenoids such as xiamycin (-9.3), thyrsiferol (-9.2), liouvilloside B (-8.9), liouvilloside A (-8.8), and stachyflin (-8.7) exhibited comparatively higher docking scores than the referral drug remdesivir (-7.4), and favipiravir (-5.7) against the target SARS-CoV-2-RdRp. The above in silico investigations concluded that stachyflin is the most 'lead' candidate with the most potential against SARS-CoV-2. Previously, stachyflin also exhibited potential activity against HSV-1 and CoV-A59 within IC50, 0.16-0.82 µM. Therefore, some additional pharmacological studies are needed to develop 'stachyflin' as a drug against SARS-CoV-2.
  16. The Modulation of NMDA and AMPA/Kainate Receptors by Tocotrienol-Rich Fraction and Α-Tocopherol in Glutamate-Induced Injury of Primary Astrocytes
    Abedi Z, Khaza'ai H, Vidyadaran S, Mutalib MSA
    Biomedicines, 2017 Dec 01;5(4).
    PMID: 29194360 DOI: 10.3390/biomedicines5040068
    Astrocytes are known as structural and supporting cells in the central nervous system (CNS). Glutamate, as a main excitatory amino acid neurotransmitter in the mammalian central nervous system, can be excitotoxic, playing a key role in many chronic neurodegenerative diseases. The aim of the current study was to elucidate the potential of vitamin E in protecting glutamate-injured primary astrocytes. Hence, primary astrocytes were isolated from mixed glial cells of C57BL/6 mice by applying the EasySep® Mouse CD11b Positive Selection Kit, cultured in Dulbecco's modified Eagle medium (DMEM) and supplemented with special nutrients. The IC20 and IC50 values of glutamate, as well as the cell viability of primary astrocytes, were assessed with 100 ng/mL, 200 ng/mL, and 300 ng/mL of tocotrienol-rich fraction (TRF) and alpha-tocopherol (α-TCP), as determined by an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The mitochondrial membrane potential (MMP) detected in primary astrocytes was assessed with the same concentrations of TRF and α-TCP. The expression levels of the ionotropic glutamate receptor genes (Gria2, Grin2A, GRIK1) were independently determined using RT-PCR. The purification rate of astrocytes was measured by a flow-cytometer as circa 79.4%. The IC20 and IC50 values of glutamate were determined as 10 mM and 100 mM, respectively. Exposure to 100 mM of glutamate in primary astrocytes caused the inhibition of cell viability of approximately 64.75% and 61.10% in pre- and post-study, respectively (p < 0.05). Both TRF and α-TCP (at the lowest and highest concentrations, respectively) were able to increase the MMP to 88.46% and 93.31% pre-treatment, and 78.43% and 81.22% post-treatment, respectively. Additionally, the findings showed a similar pattern for the expression level of the ionotropic glutamate receptor genes. Increased extracellular calcium concentrations were also observed, indicating that the presence of vitamin E altered the polarization of astrocytes. In conclusion, α-TCP showed better recovery and prophylactic effects as compared to TRF in the pre-treatment of glutamate-injured primary astrocytes.
  17. Fulltext Effect of Different Collection Times of Dermal Fibroblast Conditioned Medium (DFCM) on In Vitro Re-Epithelialisation Process
    Abdul Ghani N', Razali RA, Chowdhury SR, Fauzi MB, Bin Saim A, Ruszymah BHI, et al.
    Biomedicines, 2022 Dec 09;10(12).
    PMID: 36551960 DOI: 10.3390/biomedicines10123203
    A key event in wound healing is re-epithelialisation, which is mainly regulated via paracrine signalling of cytokines, chemokines, and growth factors secreted by fibroblasts. Fibroblast-secreted factors can be collected from the used culture medium, known as dermal fibroblast conditioned medium (DFCM). The goal of this study was to optimise the culture condition to acquire DFCM and evaluate its effect on keratinocyte attachment, proliferation, migration, and differentiation. Confluent fibroblasts were cultured with serum-free keratinocyte-specific (DFCM-KM) and fibroblast-specific (DFCM-FM) medium at different incubation times (Days 1, 2, and 3). DFCM collected after 3 days of incubation (DFCM-KM-3 and DFCM-FM-3) contained a higher protein concentration compared to other days. Supplementation of DFCM-KM-3 enhanced keratinocyte attachment, while DFCM-FM-3 significantly increased the keratinocyte wound-healing rate, with an increment of keratinocyte area and collective cell migration, which was distinctly different from DFCM-KM-3 or control medium. Further analysis confirmed that the presence of calcium at higher concentrations in DFCM-FM facilitated the changes. The confluent dermal fibroblasts after 3 days of incubation with serum-free culture medium produced higher proteins in DFCM, resulting in enhanced in vitro re-epithelialisation. These results suggest that the delivery of DFCM could be a potential treatment strategy for wound healing.
  18. Fulltext Genetics of Cholesterol-Related Genes in Metabolic Syndrome: A Review of Current Evidence
    Wong SK, Ramli FF, Ali A, Ibrahim N'
    Biomedicines, 2022 Dec 13;10(12).
    PMID: 36551995 DOI: 10.3390/biomedicines10123239
    Metabolic syndrome (MetS) refers to a cluster of metabolic dysregulations, which include insulin resistance, obesity, atherogenic dyslipidemia and hypertension. The complex pathogenesis of MetS encompasses the interplay between environmental and genetic factors. Environmental factors such as excessive nutrients and sedentary lifestyle are modifiable and could be improved by lifestyle modification. However, genetic susceptibility to MetS, a non-modifiable factor, has attracted the attention of researchers, which could act as the basis for future diagnosis, prognosis, and therapy for MetS. Several cholesterol-related genes associated with each characteristic of MetS have been identified, such as apolipoprotein, lipoprotein lipase (LPL), cholesteryl ester transfer protein (CETP) and adiponectin. This review aims to summarize the genetic information of cholesterol-related genes in MetS, which may potentially serve as biomarkers for early prevention and management of MetS.
  19. Fulltext Synchronous Breast and Cervical Carcinoma: A Genetic Point of View
    Yahya MM, Ismail MP, Ramanathan S, Kadir MN, Azhar A, Ibrahim NBC, et al.
    Biomedicines, 2023 Feb 11;11(2).
    PMID: 36831061 DOI: 10.3390/biomedicines11020525
    Breast carcinoma is the most common cancer of women in Malaysia. The most common sites of metastasis are the lung, liver, bone and brain. A 45-year-old lady was diagnosed with left invasive breast carcinoma stage IV (T4cN1M1) with axillary lymph nodes and lung metastasis. She was noted to have a cervical mass through imaging, and biopsy showed CIN III. Post chemotherapy, the patient underwent left simple mastectomy with examination under anaesthesia of the cervix, cystoscopy and staging. The cervical histopathological examination (HPE) showed squamous cell carcinoma, and clinical staging was 2A. The breast tissue HPE showed invasive carcinoma with triple receptors positivity. The patient was given tamoxifen and put on concurrent chemoradiotherapy (CCRT) for the cervical cancer. The management of each pathology of this patient involved a multi-disciplinary team that included surgeons, oncologists, gynaecologists, pathologists and radiologists. Due to the complexity of the case with two concurrent cancers, the gene expression profiles may help predict the patient's clinical outcome.
  20. Fulltext The Effects of Probiotics on Small Intestinal Microbiota Composition, Inflammatory Cytokines and Intestinal Permeability in Patients with Non-Alcoholic Fatty Liver Disease
    Ayob N, Muhammad Nawawi KN, Mohamad Nor MH, Raja Ali RA, Ahmad HF, Oon SF, et al.
    Biomedicines, 2023 Feb 20;11(2).
    PMID: 36831176 DOI: 10.3390/biomedicines11020640
    The prevalence of non-alcoholic fatty liver disease (NAFLD) has soared globally. As our understanding of the disease grows, the role of the gut-liver axis (GLA) in NAFLD pathophysiology becomes more apparent. Hence, we focused mainly on the small intestinal area to explore the role of GLA. We looked at how multi-strain probiotics (MCP® BCMC® strains) containing six different Lactobacillus and Bifidobacterium species affected the small intestinal gut microbiota, inflammatory cytokines, and permeability in NAFLD patients. After six months of supplementation, biochemical blood analysis did not show any discernible alterations in either group. Five predominant phyla known as Actinobacteria, Proteobacteria, Firmicutes, Bacteroidota and Fusobacteria were found in NAFLD patients. The probiotics group demonstrated a significant cluster formation of microbiota composition through beta-diversity analysis (p < 0.05). This group significantly reduced three unclassifiable species: unclassified_Proteobacteria, unclassified_Streptococcus, and unclassified_Stenotrophomonas. In contrast, the placebo group showed a significant increase in Prevotella_melaninogenica and Rothia_mucilaginosa, which were classified as pathogens. Real-time quantitative PCR analysis of small intestinal mucosal inflammatory cytokines revealed a significant decrease in IFN-γ (-7.9 ± 0.44, p < 0.0001) and TNF-α (-0.96 ± 0.25, p < 0.0033) in the probiotics group but an increase in IL-6 (12.79 ± 2.24, p < 0.0001). In terms of small intestinal permeability analysis, the probiotics group, unfortunately, did not show any positive changes through ELISA analysis. Both probiotics and placebo groups exhibited a significant increase in the level of circulating zonulin (probiotics: 107.6 ng/mL ± 124.7, p = 0.005 vs. placebo: 106.9 ng/mL ± 101.3, p = 0.0002) and a significant decrease in circulating zonula occluden-1 (ZO-1) (probiotics: -34.51 ng/mL ± 18.38, p < 0.0001 vs. placebo: -33.34 ng/mL ± 16.62, p = 0.0001). The consumption of Lactobacillus and Bifidobacterium suggested the presence of a well-balanced gut microbiota composition. Probiotic supplementation improves dysbiosis in NAFLD patients. This eventually stabilised the expression of inflammatory cytokines and mucosal immune function. To summarise, more research on probiotic supplementation as a supplement to a healthy diet and lifestyle is required to address NAFLD and its underlying causes.
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