Aroma Profile, Chemical Composition and Antiproliferative Activity of the Hydrodistilled Essential Oil of a Rare Salvia Species (Salvia greggii)
Authors :
Ismail Abaza,Nour Aboalhaija,Alhasan Alsalman,Wamidh Talib &Fatma Afifi
Abstract : The present study deals with the gas chromatography/mass spectrometry (GC/ MS) analysis of the aroma profile of different aerial organs obtained by solid-phase microextraction (SPME) and that of the hydro distilled essential oil of the fresh leaves and flowers of Salvia greggii A. Gray grown in Jordan. Oxygenated sesquiterpenes dominated the hydrodistilled oils of the leaves and flowers with guaiol (35.60 % and 31.92 %, respectively) and patchouli alcohol (16.30 % and 16.88 %, respectively) as the main constituents. Alpha-pinene, camphene, limonene, and γ-terpinene were detected as the major hydrocarbon monoterpenes and 1,8-cineol, camphor, and isobornyl acetate as the major oxygenated monoterpenes. The antiproliferative activity of the leaf essential oil was screened on MCF-7 and HCT116 cell lines. The essential oil exhibited a promising dosedependent inhibition of cell growth with low IC50’s (MCF-7: 35.35 μg/mL; HCT116: 23.57 μg/mL) with a high safety profile against the normal Vero cell line compared to the positive control Doxorubicin.
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Evaluation of the Single and Combined Antibacterial Efficiency of the Leaf Essential Oils of Four Common Culinary herbs: Dill, Celery, Coriander and Fennel Grown in Jordan
Authors : Al-Hasan Alsalman,Nour Aboalhaija,Wamidh Talib,Ismail Abaza &Fatma Afifi
Abstract : This study aimed to determine the volatile oil composition of the fresh leaves of dill, celery, coriander, and fennel, grown in Jordan, and to evaluate the antimicrobial activity of the essential oils individually and in binary (50:50) and quaternary (25:25:25:25) mixtures. The volatile oils, obtained by hydrodistillation, were analysed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). In vitro antimicrobial activities of the essential oils were evaluated against Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, and Candida albicans. Using the microtiter plate dilution method minimal inhibitory concentrations (MICs) of the essential oils were determined and the checkerboard method was then used to investigate the antimicrobial efficacy of the essential oil combinations by means of the fractional inhibitory concentration index (FICI). Dill and celery samples were rich in monoterpene hydrocarbons, while the oils of fennel and coriander were dominated by non-terpenoid compounds. In antimicrobial experiments, the essential oil of dill yielded the best activity against all tested microorganisms. In binary combination of the essential oils, best results were detected in a combination of dill with coriander against B. subtilis and P. aeruginosa, and fennel with coriander against E. coli and P. aeruginosa. The present study is the first evaluation of the volatile oil composition and determination of the antimicrobial activities of the fresh leaves of dill, celery, coriander, and fennel in binary and quaternary combinations. Additive or synergistic effects were detected in certain binary oil combinations while indifferent and antagonist effects were noticed in other mixtures.
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Inhibitory Immune Checkpoint Receptors and Ligands as Prognostic Biomarkers in COVID-19 Patients
Authors : Mohammad A. Al-Mterin1, Alhasan Alsalman1 and Eyad Elkord1,2*
Abstract : Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2. During T-cell activation, the immune system uses different checkpoint pathways to maintain co-inhibitory and co-stimulatory signals. In COVID-19, expression of immune checkpoints (ICs) is one of the most important manifestations, in addition to lymphopenia and inflammatory cytokines, contributing to worse clinical outcomes. There is a controversy whether upregulation of ICs in COVID-19 patients might lead to T-cell exhaustion or activation. This review summarizes the available studies that investigated IC receptors and ligands in COVID-19 patients, as well as their effect on T-cell function. Several IC receptors and ligands, including CTLA-4, BTLA, TIM-3, VISTA, LAG-3, TIGIT, PD-1, CD160, 2B4, NKG2A, Galectin-9, Galectin-3, PD-L1, PD-L2, LSECtin, and CD112, were upregulated in COVID-19 patients. Based on the available studies, there is a possible relationship between disease severity and increased expression of IC receptors and ligands. Overall, the upregulation of some ICs could be used as a prognostic biomarker for disease severity.
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Role of T Regulatory Cells and Myeloid-Derived Suppressor Cells in COVID-19
Authors : Alhasan Alsalman
,1Mohammad A. Al-Mterin
,1and Eyad Elkord
1,2
Abstract : Coronavirus disease 2019 (COVID-19) has been raised as a pandemic disease since December 2019. Immunosuppressive cells including T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs) are key players in immunological tolerance and immunoregulation; however, they contribute to the pathogenesis of different diseases including infections. Tregs have been shown to impair the protective role of CD8+ T lymphocytes against viral infections. In COVID-19 patients, most studies reported reduction, while few other studies found elevation in Treg levels. Moreover, Tregs have a dual role, depending on the different stages of COVID-19 disease. At early stages of COVID-19, Tregs have a critical role in decreasing antiviral immune responses, and consequently reducing the viral clearance. On the other side, during late stages, Tregs reduce inflammation-induced organ damage. Therefore, inhibition of Tregs in early stages and their expansion in late stages have potentials to improve clinical outcomes. In viral infections, MDSC levels are highly increased, and they have the potential to suppress T cell proliferation and reduce viral clearance. Some subsets of MDSCs are expanded in the blood of COVID-19 patients; however, there is a controversy whether this expansion has pathogenic or protective effects in COVID-19 patients. In conclusion, further studies are required to investigate the role and function of immunosuppressive cells and their potentials as prognostic biomarkers and therapeutic targets in COVID-19 patients.
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Associations of Complete Blood Count Parameters with Disease-Free Survival in Right- and Left-Sided Colorectal Cancer Patients
Authors : Alhasan Alsalman 1,Mohammad A. Al-Mterin 1ORCID,Ala Abu-Dayeh 2,Ferial Alloush 2,Khaled Murshed 2ORCID andEyad Elkord 1,3
Abstract : Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Some complete blood count (CBC) parameters are found to be associated with CRC prognosis. In this study, ninety-seven pretreated CRC patients were included, and the patients were divided into two groups: left-sided and right-sided, depending on the anatomical location of the tumor. Based on clinicopathologic features including tumor budding, disease stages, and tumor anatomical location, levels of CBC parameters were compared, and disease-free survivals (DFS) were determined. There were differences between patients with different tumor budding scores for only three parameters, including red cell distribution width (RDW), numbers of platelets, and mean platelet volume (MPV). Furthermore, numbers of WBCs, monocytes, and MPV in CRC patients with early disease stages were higher than those with advanced stages. However, levels of eosinophil in CRC patients with advanced stages were higher than those with early stages. Depending on the tumor anatomical location, we observed that numbers of red blood cells (RBCs), hemoglobin (Hgb), and hematocrit (Hct) in CRC patients with left-sided tumors were higher than those with right-sided tumors. We found that low levels of MPV were associated with shorter DFS. However, high levels of eosinophils were associated with shorter DFS in all CRC patients. When patients were divided based on the tumor anatomical location, higher levels of MPV, MCHC, and Hgb were associated with better DFS in the left-sided but not right-sided CRC patients. However, left-sided, but not right-sided, CRC patients with high levels of eosinophil and RDW had shorter DFS. Furthermore, right-sided, but not left-sided, CRC patients with high levels of platelets tended to have a shorter DFS. Our data show that MPV and eosinophils could serve as potential prognostic biomarkers in pre-treatment CRC patients, regardless of the tumor anatomical location. Additionally, lower levels of MPV, MCHC, and Hgb, and high levels of eosinophils and RDW could be negative predictive biomarkers in left-sided CRC patients. View Full-Text
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Associations of different immune checkpoints-expressing CD4+ Treg/ T cell subsets with disease-free survival in colorectal cancer patients
Authors : Mohammad A. Al-Mterin, Khaled Murshed, Alhasan Alsalman, Ala Abu-Dayeh & Eyad Elkord
Abstract : There are different subsets of T regulatory cells (Tregs), orchestrating critical roles in the regulation of anti-tumor immunity in colorectal cancer (CRC). In this study, we report that a high frequency of circulating CD4+FoxP3+ Tregs was associated with poorer disease-free survival (DFS), while their higher frequencies in tumor-infiltrating CD4+ Tregs was associated with better DFS. We further investigated such associations with four Tregs/T cells expressing or lacking FoxP3 and Helios (FoxP3±Helios±). For the first time, we report that a high frequency of circulating CD4+FoxP3+Helios+ Tregs was associated with poorer DFS, while a high frequency of tumor-infiltrating CD4+FoxP3−Helios− T cells was associated with poorer DFS. In the four FoxP3±Helios± T cell subsets expressing any of the immune checkpoints (ICs) investigated, we found that a high frequency of CD4+FoxP3+Helios−PD-1+ Tregs in circulation was associated with worse DFS. We also found that high frequencies of FoxP3+Helios+CTLA-4+ Tregs, FoxP3+Helios−CTLA-4+ Tregs, and FoxP3−Helios+CTLA-4+ CD4+ T cells in circulation were associated with worse DFS. In contrast, high frequencies of CD4+TIM-3+ T cells, FoxP3+Helios+TIM-3+ Tregs, and FoxP3−Helios+TIM-3+ CD4+ T cells in circulation were associated with longer DFS. Our data show that certain CD4+ Treg/T cell subsets could serve as independent predictive biomarkers in CRC patients. Identification of the exact subpopulations contributing to clinical outcomes is critical for prognoses and therapeutic targeting.
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Circulating and Tumor-Infiltrating Immune Checkpoint-Expressing CD8+ Treg/T Cell Subsets and Their Associations with Disease-Free Survival in Colorectal Cancer Patients
Authors : Alhasan Alsalman 1,Mohammad A. Al-Mterin 1ORCID,Khaled Murshed 2ORCID,Ferial Alloush 2,Samia T. Al-Shouli 3ORCID,Salman M. Toor 4ORCID andEyad Elkord 1,5,*ORCID
Abstract : T cells in the tumor microenvironment (TME) have diverse roles in anti-tumor immunity, including orchestration of immune responses and anti-tumor cytotoxic attack. However, different T cell subsets may have opposing roles in tumor progression, especially in inflammation-related cancers such as colorectal cancer (CRC). In this study, we phenotypically characterized CD3+CD4- (CD8+) T cells in colorectal tumor tissues (TT), normal colon tissues (NT) and in circulation of CRC patients. We investigated the expression levels of key immune checkpoints (ICs) and Treg-related markers in CD8+ T cells. Importantly, we investigated associations between different tumor-infiltrating CD8+ T cell subpopulations and disease-free survival (DFS) in CRC patients. We found that FoxP3 expression and ICs including PD-1, CTLA-4, TIM-3, and LAG-3 were significantly increased in tumor-infiltrating CD8+ T cells compared with NT and peripheral blood. In the TME, we found that TIM-3 expression was significantly increased in patients with early stages and absent lymphovascular invasion (LVI) compared to patients with advanced stages and LVI. Importantly, we report that high levels of certain circulating CD8+ T cell subsets (TIM-3-expressing, FoxP3−Helios−TIM-3+ and FoxP3−Helios+TIM-3+ cells) in CRC patients were associated with better DFS. Moreover, in the TME, we report that elevated levels of CD25+ and TIM-3+ T cells, and FoxP3+Helios−TIM-3+ Tregs were associated with better DFS. View Full-Text
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