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Fulltext The CD14 C-260T single nucleotide polymorphism (SNP) modulates monocyte/macrophage activation in treated HIV-infected individuals

Rajasuriar R, Kong YY, Nadarajah R, Abdullah NK, Spelman T, Yuhana MY, et al.

J Transl Med, 2015;13:30.
PMID: 25622527 DOI: 10.1186/s12967-015-0391-6

HIV-infected individuals have an increased risk of cardiovascular disease (CVD). T-allele carriers of the CD14 C-260T single-nucleotide polymorphism (SNP) have reported increased expression of the LPS-binding receptor, CD14 and inflammation in the general population. Our aim was to explore the relationship of this SNP with monocyte/macrophage activation and inflammation and its association with sub-clinical atherosclerosis in HIV-infected individuals.
Fulltext Multiple pathways are responsible for anti-inflammatory and cardiovascular activities of Hordeum vulgare L

Gul S, Ahmed S, Kifli N, Uddin QT, Batool Tahir N, Hussain A, et al.

J Transl Med, 2014;12:316.
PMID: 25428431 DOI: 10.1186/s12967-014-0316-9

Hordeum vulgare L. (HV or barley) is used by traditional healers to treat various inflammatory and cardiovascular diseases, without the knowledge of pharmacologic rationale behind its actions. This study was designed to explore the potential scientific mechanism(s) that could explain the use of Hordeum vulgare in traditional medicine as a treatment for various inflammatory and cardiovascular diseases.
Fulltext Immuno-pathomechanism of liver fibrosis: targeting chemokine CCL2-mediated HIV:HCV nexus

Ansari AW, Schmidt RE, Shankar EM, Kamarulzaman A

J Transl Med, 2014;12:341.
PMID: 25528160 DOI: 10.1186/s12967-014-0341-8

Even in the era of successful combination antiretroviral therapy (cART), co-infection of Hepatitis C virus (HCV) remains one of the leading causes of non-AIDS-related mortality and morbidity among HIV-positive individuals as a consequence of accelerated liver fibrosis and end-stage liver disease (ESLD). The perturbed liver microenvironment and induction of host pro-inflammatory mediators in response to HIV and HCV infections, play a pivotal role in orchestrating the disease pathogenesis and clinical outcomes. How these viruses communicate each other via chemokine CCL2 and exploit the liver specific cellular environment to exacerbate liver fibrosis in HIV/HCV co-infection setting is a topic of intense discussion. Herein, we provide recent views and insights on potential mechanisms of CCL2 mediated immuno-pathogenesis, and HIV-HCV cross-talk in driving liver inflammation. We believe CCL2 may potentially serve an attractive target of anti-fibrotic intervention against HIV/HCV co-infection associated co-morbidities.
Fulltext A randomised controlled trial on hypolipidemic effects of Nigella Sativa seeds powder in menopausal women

Ibrahim RM, Hamdan NS, Mahmud R, Imam MU, Saini SM, Rashid SN, et al.

J Transl Med, 2014;12:82.
PMID: 24685020 DOI: 10.1186/1479-5876-12-82

The risk of cardiovascular diseases (CVD) is increased tremendously among menopausal women, and there is an increasing demand for alternative therapies for managing factors like dyslipidemia that contribute to CVD development.
Fulltext Methods and matrices: approaches to identifying miRNAs for nasopharyngeal carcinoma

Plieskatt JL, Rinaldi G, Feng Y, Levine PH, Easley S, Martinez E, et al.

J Transl Med, 2014;12:3.
PMID: 24393330 DOI: 10.1186/1479-5876-12-3

Nasopharyngeal carcinoma (NPC) is a solid tumor of the head and neck. Multimodal therapy is highly effective when NPC is detected early. However, due to the location of the tumor and the absence of clinical signs, early detection is difficult, making a biomarker for the early detection of NPC a priority. The dysregulation of small non-coding RNAs (miRNAs) during carcinogenesis is the focus of much current biomarker research. Herein, we examine several miRNA discovery methods using two sample matrices to identify circulating miRNAs (c-miRNAs) associated with NPC.
Fulltext Impact of passing mesenchymal stem cells through smaller bore size needles for subsequent use in patients for clinical or cosmetic indications

Mamidi MK, Singh G, Husin JM, Nathan KG, Sasidharan G, Zakaria Z, et al.

J Transl Med, 2012;10:229.
PMID: 23171323 DOI: 10.1186/1479-5876-10-229

Numerous preclinical and clinical studies have investigated the regenerative potential and the trophic support of mesenchymal stem cells (MSCs) following their injection into a target organ. Clinicians favor the use of smallest bore needles possible for delivering MSCs into vascular organs like heart, liver and spleen. There has been a concern that small needle bore sizes may be detrimental to the health of these cells and reduce the survival and plasticity of MSCs.
Fulltext Aberrant monocyte responses predict and characterize dengue virus infection in individuals with severe disease

Yong YK, Tan HY, Jen SH, Shankar EM, Natkunam SK, Sathar J, et al.

J Transl Med, 2017 05 31;15(1):121.
PMID: 28569153 DOI: 10.1186/s12967-017-1226-4

BACKGROUND: Currently, several assays can diagnose acute dengue infection. However, none of these assays can predict the severity of the disease. Biomarkers that predicts the likelihood that a dengue patient will develop a severe form of the disease could permit more efficient patient triage and allows better supportive care for the individual in need, especially during dengue outbreaks.
METHODS: We measured 20 plasma markers i.e. IFN-γ, IL-10, granzyme-B, CX3CL1, IP-10, RANTES, CXCL8, CXCL6, VCAM, ICAM, VEGF, HGF, sCD25, IL-18, LBP, sCD14, sCD163, MIF, MCP-1 and MIP-1β in 141 dengue patients in over 230 specimens and correlate the levels of these plasma markers with the development of dengue without warning signs (DWS-), dengue with warning signs (DWS+) and severe dengue (SD).
RESULTS: Our results show that the elevation of plasma levels of IL-18 at both febrile and defervescence phase was significantly associated with DWS+ and SD; whilst increase of sCD14 and LBP at febrile phase were associated with severity of dengue disease. By using receiver operating characteristic (ROC) analysis, the IL-18, LBP and sCD14 were significantly predicted the development of more severe form of dengue disease (DWS+/SD) (AUC = 0.768, P
Precision medicine in nasopharyngeal carcinoma: comprehensive review of past, present, and future prospect

Siak PY, Heng WS, Teoh SSH, Lwin YY, Cheah SC

J Transl Med, 2023 Nov 06;21(1):786.
PMID: 37932756 DOI: 10.1186/s12967-023-04673-8

Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with high propensity for lymphatic spread and distant metastasis. It is prominent as an endemic malignancy in Southern China and Southeast Asia regions. Studies on NPC pathogenesis mechanism in the past decades such as through Epstein Barr Virus (EBV) infection and oncogenic molecular aberrations have explored several potential targets for therapy and diagnosis. The EBV infection introduces oncoviral proteins that consequently hyperactivate many promitotic pathways and block cell-death inducers. EBV infection is so prevalent in NPC patients such that EBV serological tests were used to diagnose and screen NPC patients. On the other hand, as the downstream effectors of oncogenic mechanisms, the promitotic pathways can potentially be exploited therapeutically. With the apparent heterogeneity and distinct molecular aberrations of NPC tumor, the focus has turned into a more personalized treatment in NPC. Herein in this comprehensive review, we depict the current status of screening, diagnosis, treatment, and prevention in NPC. Subsequently, based on the limitations on those aspects, we look at their potential improvements in moving towards the path of precision medicine. The importance of recent advances on the key molecular aberration involved in pathogenesis of NPC for precision medicine progression has also been reported in the present review. Besides, the challenge and future outlook of NPC management will also be highlighted.
Fulltext Advancing stem cell therapy from bench to bedside: lessons from drug therapies

Srijaya TC, Ramasamy TS, Kasim NH

J Transl Med, 2014;12:243.
PMID: 25182194 DOI: 10.1186/s12967-014-0243-9

The inadequacy of existing therapeutic tools together with the paucity of organ donors have always led medical researchers to innovate the current treatment methods or to discover new ways to cure disease. Emergence of cell-based therapies has provided a new framework through which it has given the human world a new hope. Though relatively a new concept, the pace of advancement clearly reveals the significant role that stem cells will ultimately play in the near future. However, there are numerous uncertainties that are prevailing against the present setting of clinical trials related to stem cells: like the best route of cell administration, appropriate dosage, duration and several other applications. A better knowledge of these factors can substantially improve the effectiveness of disease cure or organ repair using this latest therapeutic tool. From a certain perspective, it could be argued that by considering certain proven clinical concepts and experience from synthetic drug system, we could improve the overall efficacy of cell-based therapies. In the past, studies on synthetic drug therapies and their clinical trials have shown that all the aforementioned factors have critical ascendancy over its therapeutic outcomes. Therefore, based on the knowledge gained from synthetic drug delivery systems, we hypothesize that by employing many of the clinical approaches from synthetic drug therapies to this new regenerative therapeutic tool, the efficacy of stem cell-based therapies can also be improved.
Fulltext Global prevalence of myasthenia gravis and the effectiveness of common drugs in its treatment: a systematic review and meta-analysis

Salari N, Fatahi B, Bartina Y, Kazeminia M, Fatahian R, Mohammadi P, et al.

J Transl Med, 2021 Dec 20;19(1):516.
PMID: 34930325 DOI: 10.1186/s12967-021-03185-7

BACKGROUND: Myasthenia gravis is a neuromuscular autoimmune disorder characterized by weakness and disability in the voluntary muscles. There have been several preliminary studies on the epidemiology of myasthenia gravis in different parts of the world and the effectiveness of common drugs in its treatment, but there has been no comprehensive study of the efficacy of common drugs in the treatment of myasthenia gravis. Therefore, this study aimed to determine the epidemiology of myasthenia gravis globally and the effectiveness of common drugs in its treatment using systematic review and meta-analysis.
METHODS: Research studies were extracted from IranDoc, MagIran, IranMedex, SID, ScienceDirect, Web of Sciences (WoS), ProQuest, Medline (PubMed), Scopus and Google Scholar based on Cochran's seven-step guidelines using existing keywords extracted in MeSH browser. The I2 test was used to calculate the heterogeneity of studies, and Begg and Mazumdar rank correlation tests were used to assess publication bias. Data were analyzed using Comprehensive Meta-Analysis software (Version 2).
RESULTS: In the search for descriptive studies based on the research question, 7374 articles were found. After deleting articles unrelated to the research question, finally, 63 articles with a sample size of 1,206,961,907 people were included in the meta-analysis. The prevalence of MG worldwide was estimated to be 12.4 people (95% CI 10.6-14.5) per 100,000 population. For analytical studies on the effectiveness of common myasthenia gravis drugs, 4672 articles were found initially, and after removing articles unrelated to the research question, finally, 20 articles with a sample size of 643 people in the drug group and 619 people in the placebo group were included in the study. As a result of the combination of studies, the difference between the mean QMGS score index after taking Mycophenolate and Immunoglobulin or plasma exchange drugs in the group of patients showed a significant decrease of 1.4 ± 0.77 and 0.62 ± 0.28, respectively (P < 0.01).
CONCLUSION: The results of systematic review of drug evaluation in patients with myasthenia gravis showed that Mycophenolate and Immunoglobulin or plasma exchange drugs have positive effects in the treatment of MG. It also represents the positive effect of immunoglobulin or plasma exchange on reducing SFEMG index and QMGS index and the positive effect of Mycophenolate in reducing MG-ADL index, SFEMG and Anti-AChR antibodies index. In addition, based on a meta-analysis of the random-effect model, the overall prevalence of MG in the world is 12.4 people per 100,000 population, which indicates the urgent need for attention to this disease for prevention and treatment.
Pharmacological Vitamin C-induced high H2O2 generation mediates apoptotic cell death by caspase 3/7 activation in breast cancer tumor spheroids

Mussa A, Hamid M, Hajissa K, Murtadha AH, Al-Hatamleh MAI, Mokhtar NF, et al.

J Transl Med, 2025 Jan 08;23(1):31.
PMID: 39780231 DOI: 10.1186/s12967-024-06016-7

BACKGROUND: Pharmacological vitamin C (Vit-C), or high-dose Vit-C has recently gained attention as a potential cancer therapeutic. However, the anticancer activity of Vit-C has not been investigated in realistic 3D models of human cancers, especially with respect to breast cancer (BC), and its potential benefits remain under debate. Herein, we investigate the activity and mechanism of action of pharmacological Vit-C on two BC tumor spheroids.
METHODS: We developed two distinct types of BC tumor spheroids from MDA-MB-231 and MCF-7 cells. The spheroids underwent treatment with a range of concentrations of pharmacological Vit-C (1, 5, 10, 15, and 20 mM). Assessments were conducted to determine the cell viability, H2O2 levels, glutathione-to-glutathione disulfide (GSH/GSSG) ratios, and apoptosis. Both flow cytometry analyses of Annexin V/PI staining and caspase3/7 activity assay were used to check apoptosis.
RESULTS: We showed that Vit-C induced dose-dependent cell death in both types of tumor spheroids, primarily driven by elevated H2O2 production and a concomitant oxidative stress imbalance induced by the GSH depletion. The high levels of H2O2 generated by Vit-C triggered the apoptosis of spheroids. In MCF-7 spheroids, Vit-C-induced H2O2 production was higher, with a more pronounced decrease in the GSH/GSSG ratio, indicating greater susceptibility to oxidative stress-induced cell death. However, MDA-MB-231 spheroids exhibited a more severe cytotoxic response.
CONCLUSIONS: This study reveals that Vit-C induces oxidative stress-mediated cell death in both non-aggressive and aggressive BC spheroids. Unlike traditional in vitro studies, this work provides novel insights into the response of two BC tumor subtypes to Vit-C, demonstrating its potential as a targeted common therapy for BC.
Fulltext Cellular crosstalk in the bone marrow niche

Huang Z, Iqbal Z, Zhao Z, Liu J, Alabsi AM, Shabbir M, et al.

J Transl Med, 2024 Dec 03;22(1):1096.
PMID: 39627858 DOI: 10.1186/s12967-024-05900-6

The bone marrow niche is a special microenvironment that comprises elements, including hematopoietic stem cells, osteoblasts, and endothelial cells, and helps maintain their characteristic functions. Here, we elaborate on the crosstalk between various cellular components, hematopoietic stem cells, and other cells in the bone marrow niche. We further explain the mechanism of preserving equilibrium in the bone marrow niche, which is crucial for the directional regulation of bone reconstruction and repair. Additionally, we elucidate the intercommunication among osteocytes, the regulation of osteoblast maturation and activation by lymphocytes, the deficiency of megakaryocytes that can markedly impair osteoblast formation, and the mechanism of interaction between macrophages and mesenchymal stem cells in the bone marrow niche. Finally, we discussed the new immunotherapies for bone tumors in the BM niche. In this review, we aimed to provide a candid overview of the crosstalk among bone marrow niche cells and to highlight new concepts underlying the unknown mechanisms of hematopoiesis and bone reconstruction. Thus, this review may provide a more comprehensive understanding of the role of these niche cells in improving hematopoietic function and help identify their therapeutic potential for different diseases in the future.