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Systemic lupus erythematosus (SLE) is characterized by systemic end-organ damage. We investigated the involvement of IRF5, TLR-7, MECP2, STAT4, and TNFSF4 genes and TNF-α, IFN-γ, IL-2, IL-12, IL-6, and IL-10 cytokines in SLE pathogenesis and in organ damage in Jordanian patients. Blood was collected from 51 patients and 50 controls. Expression levels of SLE genes in PBMCs and cytokine levels were determined using RT-PCR and ELISA, respectively. Expression levels of all genes and levels of TNF-α, IL-12, IL-6, and IL-10 were higher in SLE patients than those in controls (p<0.05), whereas IL-2 level was lower. High STAT4 (α), TNFSF4, and IL-10 levels correlated with cardiovascular damage, and high MECP2 (α) and TNF-α correlated with renal damage. Pulmonary and musculoskeletal damages correlated with high levels of TNFSF4. We concluded that STAT4 and TNFSF4 genes with TNF-α and IL-10 cytokines could be used as biomarkers to assess SLE activity and manage treatment.

Since the WHO declared coronavirus disease 2019 (COVID-19) as a pandemic, huge efforts were made to understand the disease, its pathogenesis, and treatment. COVID-19 is caused by severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV2), which is closely related to SARS-associated coronavirus (SARS-CoV). This article attempts to provide a timely and comprehensive review of the coronaviruses over the years, and the epidemics they caused in this century with a focus on the current pandemic COVID-19. It also covers the basics about the disease immunopathogenesis, diagnosis, prognosis, and treatment options. Although almost every single week new clinical findings are published, which change our understanding of COVID-19, this review explores and explains the disease and the treatment options available so far. In summary, many therapeutic options are being investigated to treat and/or ameliorate the symptoms of COVID-19, but none is registered and no sufficient data to support immune-based therapy beyond the context of clinical trials. For that, strengthening our immune system is the best defense at this time.

Vaccination to prevent coronavirus disease 2019 (COVID-19) emerged as a promising measure to overcome the negative consequences of the pandemic. Since university students could be considered a knowledgeable group, this study aimed to evaluate COVID-19 vaccine acceptance among this group in Jordan. Additionally, we aimed to examine the association between vaccine conspiracy beliefs and vaccine hesitancy. We used an online survey conducted in January 2021 with a chain-referral sampling approach. Conspiracy beliefs were evaluated using the validated Vaccine Conspiracy Belief Scale (VCBS), with higher scores implying embrace of conspiracies. A total of 1106 respondents completed the survey with female predominance (n = 802, 72.5%). The intention to get COVID-19 vaccines was low: 34.9% (yes) compared to 39.6% (no) and 25.5% (maybe). Higher rates of COVID-19 vaccine acceptance were seen among males (42.1%) and students at Health Schools (43.5%). A Low rate of influenza vaccine acceptance was seen as well (28.8%), in addition to 18.6% of respondents being anti-vaccination altogether. A significantly higher VCBS score was correlated with reluctance to get the vaccine (p < 0.001). Dependence on social media platforms was significantly associated with lower intention to get COVID-19 vaccines (19.8%) compared to dependence on medical doctors, scientists, and scientific journals (47.2%, p < 0.001). The results of this study showed the high prevalence of COVID-19 vaccine hesitancy and its association with conspiracy beliefs among university students in Jordan. The implementation of targeted actions to increase the awareness of such a group is highly recommended. This includes educational programs to dismantle vaccine conspiracy beliefs and awareness campaigns to build recognition of the safety and efficacy of COVID-19 vaccines.

Introduction: The rate of Jordanian tobacco smokers has been reported to be one of the highest rates in the world. The electronic cigarette (E-cig) has become an option, or an alternative, to tobacco cigarette smoking. This study was aimed to measure the perception of Jordanian adults toward E-cig use. Methods: A cross-sectional study design was used. A self-administered survey was developed and validated to solicit anonymous responses from the study participants. A convenience sample (n = 984) was recruited electronically through social media platforms. Descriptive statistics and correlation analyses were completed using the Statistical Package for the Social Sciences (SPSS). Results: More than half of the participants (53%) were females, and almost all participants had heard about E-cig (99.2%), mainly from their friends (40%) and social media (34.5%). About half of the participants were nonsmokers and around one-third of them (33.1%) were current E-cig users. The majority of the participating E-cig users had replaced tobacco with E-cig (56.4%)/All the E-cig users reported positive beliefs toward the E-cig as a safer alternative for tobacco smoking. About 45% of participants believed that the E-cig is helpful in tobacco smoking cessation, but should be highly regulated. Conclusion: This study illustrated a significant prevalence of E-cig usage among Jordanian adults. E-cig users perceived E-cig as a safer and cheaper alternative to tobacco smoking and that it helps in tobacco smoking cessation. However, health awareness campaigns are needed for the entire Jordanian community about E-cig use, related emerging health findings, and how to promote tobacco smoking cessation.

Tigecycline is a glycylcycline antibiotic approved by the FDA for the treatment of complicated infections. Despite its effectiveness, the FDA announced a warning of increasing mortality associated with its use. There is, however, no clear explanation for this side effect. Previous reports found a possible effect of tigecycline on leukocyte proliferation and proinflammatory cytokine release. We t herefore i nvestigated the effect of tigecycline on the immune components and response in Balb/c mice in vivo and in vitro. It was found that tigecycline enhanced lymphocyte proliferation and significantly increased cellular infiltration within the footpad, as based on DTH testing, but reduced the hemagglutination titer. In splenocyte cultures, tigecycline suppressed splenocyte proliferation with IC50 3-5 mmol L-1, significantly increased IL-2 secretion and reduced IL-17 secretion in a dose dependent mode. In conclusion, tigecycline is safe at therapeutic and sub-therapeutic doses, but it could still have an immunomodulatory effect at higher doses. Use of higher doses of tigecycline requires further investigation.

Marrubium vulgare (Lamiaceae) is frequently used in traditional medicine to treat many illnesses from ancient times. Its beneficial effects include antibacterial, antioedematogenic, and analgesic activities. This study was designed to evaluate the antioxidant and anti-inflammatory activities of organic and aqueous extracts of the leaves, the flowers, the stems, and the roots of Marrubium vulgare. The total phenolic and flavonoid contents as well as the antioxidant and the anti-inflammatory effects of methanol, chloroform, ethyl acetate, and aqueous extracts have been investigated by using different in-vitro methods. It was found that the ethyl acetate extract from Marrubium vulgare stems had the highest total phenolic content, while the ethyl acetate extract from the leaves yielded a high concentration of flavonoids. The ethyl acetate extract from the stems exhibited the highest activity in scavenging of 2,2-diphenyl- 1-picrylhydrazyl (DPPH), as well as in protecting erythrocytes. The leaves aqueous extract exhibited the highest ferrous chelating activity and its methanolic extract was found to be the strongest inhibitor of lipid peroxidation in β-carotene bleaching assay. The leaves chloroform extracts as well as the flowers methanol, chloroform, and ethyl acetate extracts were found to decrease the pro-inflammatory tumor necrosis factor alpha (TNF-α) cytokine levels in a dose-dependent manner. On the other hand, the flowers methanolic extract and the leaves methanol, ethyl acetate, and aqueous extracts decreased the interleukin-1 beta (IL- 1β) release. It was also found that the methanol extract from the flowers and the chloroform extract from the stems of Marrubium vulgare inhibited interleukin-8 (IL-8) release. This study provides a scientific basis for the traditional use of Marrubium vulgare as an anti-inflammatory agent and for the plant to be considered as an important resource of natural antioxidants.

Psychological stress stimulates physiological responses releasing catecholamines and corticoids, which act via corresponding receptors on immune cells, producing a shift in the cytokine balance. These responses are variable depending on the nature of stressors. The effect of the academic stress on the production of the Th1-cytokines (TNF-α, IFN-γ, IL-1β, IL-2, IL-6 and IL-8) and Th2-cytokines (IL-1ra, IL-4, IL-5 and IL-10) on 35 medical/health sciences students after completing their questionnaires was investigated. Blood samples were taken at three stages; baseline stage at the beginning, midterm and final academic examination stages. Plasma cortisol and cytokines were measured during the three stages. The last two stages were compared with the baseline non-stress period. Results of the stress induced during the final examination stage were the highest with a significant increase in cortisol release, IL-4, IL-5 and IL-1ra release with a shift in Th1:Th2 cytokines balance towards Th2. Whereby, the midterm stage did not show significant reduction in Th1-cytokines except for TNF-α, with an increase in IFN-γ level that was reduced in the third stage. Th2 cytokine, IL-1ra, had positive correlations with Th1 cytokines; IL-2 and IFN-γ in the second stage and IL-6 cytokine in the third stage. Cortisol was positively correlated with IL-8 in the last stage and heart rates had negative correlation with IL-10 in the first and last stages. Findings of this study indicate that exam stress down-regulates Th1 with a selective up-regulation of Th2-cytokines. In conclusion, Cortisol might have a role in suppressing the release of Th1- mediated cellular immune response which could increase the vulnerability among the students to infectious diseases. Keywords: Academic stress, Cortisol, Th1-cytokines, Th2-cytokines, Medical/health sciences students

Introduction: Methanolic extracts of six plants (Arbutus andrachne, Chrysanthemum coronarium, Inula viscosa, Origanum syriacum, Punica granatum, and Rosmarinus officinalis) used in traditional medicine for the treatment of bacterial and fungal infections were evaluated. The present study was conducted to evaluate the antimicrobial and anti-inflammatory activity of some medicinal plants in lowering the risk of opportunistic infections of the oral cavity caused by Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. Extracts were evaluated separately and in a mixture. Methodology: The methanolic plant extracts were tested against three opportunistic microorganisms by determining the minimum inhibitory concentration (MIC). They were also evaluated for their ability to suppress the release of the pro-inflammatory cytokine IL-6 while not suppressing the release of the anti-inflammatory cytokine IL-10 from peripheral blood mononuclear cells using ELISA. Results: All extracts showed both antimicrobial and anti-inflammatory activities. However, O. syriacum exhibited the highest antimicrobial activity for the three microorganisms among all of the tested extracts (MIC S. aureus: 1 mg/mL; P. aeruginosa: 2 mg/mL; and C. albicans: 1 mg/mL). The extracts inhibited the expression of the pro-inflammatory cytokine IL-6 with apparent dose-dependent responses while they attenuated the secretion of the anti-inflammatory cytokine IL-10. The mixture of O. syriacum and R. officinalis showed an anti-inflammatory effect, with a synergistic antimicrobial effect. Conclusion: These findings support the idea that a diet rich in plants and herbs may contribute to the reduction of inflammation and microbial growth and may also be preventive against various infections, including those related to the oral cavity.

Hertia cheirifolia L. (Asteraceae) is traditionally used in Northern Africa to treat various inflammatory infections. However, few studies on this plant have been reported.The anti-inflammatory activity of methanol extract of H. cheirifolia leaves was investigated using different experimental models.Phytochemical analysis was performed to determine phenolic compounds. Acute toxicity of the extract (2000 mg/kg) was examined in Swiss albino mice for 14 days, before croton oil-induced ear oedema in mice, carrageenan-induced paw oedema in Swiss albino rats, cotton pellet-induced granuloma in rats and carrageenan-induced air pouch in mice were conducted. The IL-1β and TNF-α release from concanavalin A-stimulated monocytes was measured by ELISA.Methanol extract of H. cheirifolia is rich in polyphenols and flavonoids. Cinnamic acid and rutin represent the major constituents. Methanol extract up to 2000 mg/kg did not produce any toxic effects. Topical application of 2 mg/ear of the extract produced 78.7% of inhibition on ear swilling. Oral pre-treatment of rats with 200 and 400 mg/kg of the extract inhibited paw oedema by 70% and 89%, respectively. At 200 mg/kg, granuloma dry and wet weights were reduced by 41.85% and 61.72%, respectively. Moreover, the treatment with methanol extract at 1 mg/kg exerted 62.7% of inhibition on leucocytes migrated into the ear pouch. TNF-α and IL-1β release was reduced by 69% and 78%, respectively, with 1 μg/mL of the extract.Methanol extract of H. cheirifolia possesses a strong anti-inflammatory activity and may be considered an interesting source of effective anti-inflammatory compounds.

AIMS In this study, the association between multidrug resistance (MDR) and the expression of some virulence factors were evaluated in Escherichia coli strains isolated from infant faeces and fresh green vegetables. The effect of isolate origin on associated virulence factors was evaluated. In addition, genetic fingerprinting of a sample of these isolates (10 isolates from each group) was studied in order to detect any genetic relatedness among these isolates. METHODS AND RESULTS Escherichia coli isolates were divided into four groups based on their origin (human faeces or plant) and their antibiotic resistance (multiresistance or susceptible). PCR was used to investigate heat-labile and heat-stable enterotoxin genes, and four siderophore genes (aerobactin, enterobactin, salmochelin and yersiniabactin). Genetic fingerprinting of the isolates was performed using enterobacterial repetitive intergenic consensus PCR. Siderophore production was measured by a colorimetric method. Biofilm formation was evaluated by a crystal violet assay. The results of the study showed that the expression of MDR is not significantly associated with an increase in these virulence factors or with biofilm formation. However, the origin of isolates had a significant association with siderophore gene availability and consequently on the concentrations of siderophores released. Genetic fingerprinting indicated that human and plant isolates have the same clonal origin, suggesting their circulation among humans and plants. CONCLUSION Antibiotic-susceptible strains of E. coli may be as virulent as MDR strains. Results also suggest that the environment can play a potential role in selection of strains with specific virulence factors. SIGNIFICANCE AND IMPACT OF THE STUDY Antibiotic-susceptible isolates of Escherichia coli from plant or human origin can be as virulent as the multidrug resistance (MDR) ones. Genetic relatedness was detected among the isolates of plant and human origin, indicating the circulation of these bacteria among human and plants. This could imply a potential role for environmental antimicrobial resistant bacteria in human infection.

Acne vulgaris is a chronic inflammatory disorder in which Propionibacterium acnes plays a critical role in its development when it overgrows in the pilosebaceous unit. The present study was conducted to evaluate the antimicrobial and anti-inflammatory activity of fourteen Mediterranean plant extracts separately and in combinations for the treatment of acne. The methanolic plant extracts were tested against P. acnes by determining the minimum inhibitory concentration (MIC). The extracts that showed high antimicrobial activity were studied for their anti-inflammatory effect. They were evaluated for their ability to suppress the pro-inflammatory cytokines IL-1β, IL-8, IL-12 and the TNF-α release from PBMCs and mTNF-α from mouse splenocytes using ELISA assay. Rosmarinus officinalis was found to exhibit the highest antimicrobial activity amongst all of the tested extracts (MIC 0.5 mg/ml) followed by Origanum syriacum (MIC 1 mg/ml) and Punica granatum (MIC 1.25 mg/ml). 100 and 50 μg/ml ofChrysanthemum coronarium, Origanum syriacum or Inula viscosa extracts showed the most effective inhibition for the cytokine release. Six extracts had shown both antimicrobial and anti-inflammatory activities with apparent dose-dependent responses making them potential agents for the treatment of acne. Two mixtures prepared from the plants with the highest antimicrobial activity had shown synergistic antimicrobial and anti-inflammatory effect. Key words: Cytokines, minimal inhibitory concentration (MIC), enzyme-linked immunosorbent assay (ELISA), peripheral blood mononuclear cells (PBMCs), splenocytes, Propionibacterium acnes.

Influenza vaccination is the most effective method in preventing influenza and its complications. This study's objectives were to investigate the vaccination coverage and frequency and to assess knowledge, attitudes, and practices toward influenza vaccination in Jordan during the year 2012 and the 5 years preceding it. Additionally, it aimed at identifying the barriers and motivations to receive the vaccine and the factors contributing to its uptake. In May 2012, a self-administered cross-sectional survey was distributed to 3,200 adults conveniently selected across Jordan to explore influenza vaccination status, knowledge, attitudes, and practices toward the influenza vaccine. The survey response rate was 98.3%. The overall coverage rate of seasonal influenza vaccination ranged from 9.9% to 27.5%. Results of the univariate analysis revealed that males, participants older than 45 years, business owners, and university students or graduates were more likely to take the vaccine. Healthcare workers (HCW) showed higher rates than non-HCW and those with concomitant chronic diseases were more committed to receive the vaccine. Knowledge about the influenza vaccine is considered high in the Jordanian population. Fear from side effects was the major barrier, while the fear of the virus spread and outbreak was the major reason to receive the vaccine. The coverage rates were low in Jordan compared to other countries. The need for influenza vaccine campaigns and on-going education in Jordan health schools is crucial to increase the rate and remove misconceptions and negative attitudes toward vaccination.

On account of its poor prognosis and deficiency of therapeutic stratifications, triple negative breast cancer continues to form the causative platform of an incommensurate number of breast cancer deaths. Aiming at the development of potent anticancer agents as a continuum of our previous efforts, a novel series of 2-((benzimidazol-2-yl)thio)-1-arylethan-1-ones 5a–w was synthesized and evaluated for its anti-proliferative activity towards triple negative breast cancer (TNBC) MDA-MB-468 cells. Compound 5k was the most active analog against MDA-MB-468 (IC50 = 19.90 ± 1.37 µM), with 2.1-fold increased activity compared to 5-fluorouracil (IC50 = 41.26 ± 3.77 µM). Compound 5k was able to induce apoptosis in MDA-MB-468, as evidenced by the marked boosting in the percentage of florecsein isothiocyanate annexin V (Annexin V–FITC)-positive apoptotic cells (upper right (UR) + lower right (LR)) by 2.8-fold in comparison to control accompanied by significant increase in the proportion of cells at pre-G1 (the first gap phase) by 8.13-fold in the cell-cycle analysis. Moreover, a quantitative structure activity relationship (QSAR) model was established to investigate the structural requirements orchestrating the anti-proliferative activity. Finally, we established a theoretical kinetic study.

The unprecedented rates of resistance of cancer cells to traditional chemotherapeutic medications necessitated relentless exploration and drug design in an attempt to introduce safe and effective new antineoplastic agents. The latter is a particular pivotal to the treatment of solid tumors malignancies which represent the top causes of cancer deaths. Our laboratory has established a line of research to investigate potential cytotoxic agents of native plant origins. Folkloric anecdotal evidence and initial screening led us to investigate the cytotoxicity of Mercurialis annua L. (Euphorbiaceae) methanolic extract against a variety of cancer cell lines. In total, six different cell lines representing three types of common cancers were used to determine the potential antineoplastic activity of the plant extract. Our results show that the M. annua extract exhibited potent cytotoxic effect on both HRT-18 and T47D cell lines in a dose-dependent manner. HRT-18 is a colorectal adenocarcinoma cell line, while T47D is a breast cancer cell line. The calculated IC50 values of the plant extract against HRT-18 and T47D cell lines were 41 and 270 µg/ml, respectively. On the other hand, there was no appreciable inhibitory effect of the plant extract on the growth of Caco-2, MCF-7, A375-S, and WM136-1A cell lines. The inhibition of cellular growth was cell-type specific. Among the breast cancer cell lines, MCF7 and T47D, only T47D which is a human ductal breast epithelial was sensitive to the plant extract. Likewise, the human epithelial colorectal adenocarcinoma cells (Caco-2) was resistant, while the human rectum adenocarcinoma (HRT-18) was sensitive to the plant extract. Interestingly, the two human malignant melanoma cell lines; A375.S2 and WM136 1A were both resistant to the plant extract. This work is a first step towards unraveling the full pharmacologic potential of M. annua in cancer treatment. Key words: Mercurialis annua L., cancer, cytotoxic, T47D, HRT-18, plant extract.

Ethnopharmacological relevance Mercurialis annua L., Bongardia chrysogonum L., and Viscum cruciatum Sieb have been traditionally used by local herbalists in Jordan for the treatment of hematopoietic neoplasms. Aim of the study To determine the anti-cancer, anti-inflammatory and anti-microbial potentials of the three extracts against two of the most common hematopoietic malignancies in the Jordanian populations; Burkitt's lymphoma and Multiple myeloma. Materials and methods The anti-cancer activity was tested against the two cell lines (BJAB Burkitt's lymphoma and U266 multiple myeloma) using the MTT and trypan blue assays. The agar dilution assay was used to study the anti-microbial activity against Gram-positive bacteria, Gram-negative bacteria, anaerobic bacteria and yeast. The pro-inflammatory cytokines interleukin (IL) -1β, IL-8 and tumor necrosis factor-α (TNF-α) were measured in the pretreated cell lines using ELISA assay to determine the anti-inflammatory activity of Viscum cruciatum Sieb against the two cell lines. Results The results show no evidence of stimulation of tumor growth by any of the three extracts comprising cell lines from hematological malignancies, but Viscum cruciatum Sieb showed a selective anticancer activity against BJAB cells, with IC50 value of 14.21 μg/ml. The antimicrobial effect was only noticed with Viscum cruciatum extract by inhibiting Staphylococcus aureus, Candida albicans and Propionibacterium acne, but not Pseudomonas aeruginosa at MIC of 1.25, 1.25, 0.625 and

The human toll like receptor 9 (TLR9) detects differences between microbial and host DNA, based on unmethylated deoxycytidyl deoxyguanosine dinucleotide (CpG) motifs, leading to activation of both innate and adaptive immune mechanisms. The synthetic TLR9 agonist, CpG-ODN, can substitute for microbial DNA in these responses, and is in clinical trials as an immunomodulatory agent in diseases as diverse as infections, cancer and allergic disorders. Human TLR9 is expressed on cells of haematopoietic origin (principally plasmacytoid dendritic cells and B cells), but has also been described as being expressed on a number of other cell types. In order to clarify the expression and function of TLR9 in a range of cells of both haematopoietic and non-haematopoietic origin, we investigated the level of expression of TLR9 mRNA, and the ability of the cells to respond to CpG-ODN by upregulation of cell surface markers, cytokine production, cellular proliferation and activation of NFkappaB. Our data show that the cellular response to CpG-ODN depended on a threshold level of expression of TLR9. TLR9 was widely expressed amongst B cell tumours (with the exception of myeloma cell lines), but we did not find either threshold levels of expression of TLR9 or responses to CpG-ODN in several myeloma or myeloid tumour cell lines or any non-haematological tumour cell lines tested in our study. TLR9-positive cells varied significantly in their responses to CpG-ODN, and the level of TLR9 expression beyond the threshold did not correlate with the magnitude of the response to CpG-ODN. Finally, CpG-ODN induced NFkappaB activation and increased cellular proliferation in Hek293 cells that had been stably transfected with hTLR9, but did not affect the expression of surface markers or synthesis of IL-6, IL-10 or TNF-alpha. Thus both haematological and non-haematological cells expressing appropriate levels of TLR9 respond to CpG-ODN, but the nature of the TLR9-mediated response is dependent on cell type.

Stress in health sciences students has been studied extensively. Nevertheless, only few studies have been conducted on pharmacy students and nothing was done to compare stress effects on the immune responses of Pharmacy and Doctor of Pharmacy (PharmD) students. The aim of this pilot study was (1) to measure the self-reported perceived stresses, immune-related diseases and health outcomes of pharmacy and PharmD students, (2) to investigate the relationship between perceived stresses, health outcomes and immune-related diseases and (3) to compare stress induced changes in the health and immune system of pharmacy and PharmD students. The study represents a cross sectional survey using an interviewer administered questionnaire about stress and students’ health states during the fall semester of 2009/2010. At commence of this study, 222 of pharmacy and PharmD participant students (113 and 109 respectively) from the third and uppermost levels of study were picked up randomly. They were found to perceive stress related to program intensity, lack of exercise and social activities, bad nutritional routines and accommodation. Effects of increased study loads on students’ health and immune-related diseases were more pronounced on PharmD students, while showing significant changes on Pharmacy students. In general, more than 50% of students of each program got ill several times, mainly during the midterm period, had cold/flu, were under medical care and had problems in skin and/or hair. Also, PharmD students reported relatively higher levels of perceived stress and lower emotional and satisfaction quality of life compared to Pharmacy students. Results may help to increase the awareness of students to get prepared to what they might face, and may enable them to reduce the program’s negative effects.