Research Title: Pain in COVID-19. Eliva press, August 2021, ISBN: 978-16364-315-3.

Author: Sahar Majdi Jaffal, Published Year: 2021

Faculty: Science

Abstract: Coronavirus disease 2019 (COVID-19) is one of the worst pandemics, responsible for huge losses in economy and healthcare sectors all over the world. In addition to mortality, COVID-19 disease causes several types of pain during viral infection and after recovery. Inflammatory and neuropathic pain were reported in COVID-19 patients. Unfortunately, using many of the available drugs aggravated COVID-19 symptoms in patients and increased patients' susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is a need for new therapeutics that can alleviate rather than aggravate COVID-19 symptoms. In this book, the author provides an introduction to the COVID-19 disease, pain in COVID-19 patients, the involvement of pain receptors in several symptoms that frequently appear in COVID-19 patients and an opinion on potential approaches for the alleviation of COVID-19 symptoms. In more detail, the author, herein, highlights the possible involvement of the transient receptor potential (TRP) channels, cannabinoid (CB) receptors, peroxisome proliferator-activated receptors (PPAR) and opioid receptors in COVID-19 symptoms in parallel with the crosstalk between these receptors.

Keywords: Pain, COVID-19, TRP, PPAR, cannabinoid

Research Title: Laboratory Manual for Physiology. 2023, ISBN: 978-9923-0-0775-4.

Author: Sahar Majdi Jaffal, Published Year: 2023

Faculty: Science

Abstract: This laboratory manual has been designed to help students master the fundamentals of Physiology and gain an understanding of physiological concepts through different experiments and activities. By conducting the experiments in this manual, the students will be able to develop skills associated with observation, analysis and interpretation of the results. Also, the students will be familiar with the equipment and tools that are used in the experiments. Further, the laboratory reports in this manual are collected to reinforce the student's understanding. Completing the reports independently is considered as important as performing the experiments. The content of this laboratory manual was extracted from different sources to create an educational manual that can help students in basic science, allied health programs and other related fields. The manual was written in a simple way. Each experiment includes the student learning outcomes (SLOs), key terms, an introduction, the principle(s) of the experiment, the procedure for conducting the experiment, the normal ranges of parameters that are used in the experiment and the clinical application of the tests. The author would like to thank the architect Maram Jaffal for designing the book cover and drawing several figures in this manual. Other figures were downloaded with permission from different companies or websites. The author thanks all those who approved using these illustrations in this laboratory manual. The author acknowledges the administrators of ADI Global Distribution and Biopac Systems Inc. for providing permission to use figures in this manual.

Keywords: Physiology, manual, laboratory, reports

Research Title: Nongenomic activation of the GC-A enzyme by resveratrol and estradiol downstream from membrane estrogen receptors in human coronary arterial cells.

Author: Sahar Majdi Jaffal, Published Year: 2007

Nutrition, Metabolism and cardiovascular diseases, 17 (7): 508-516.

Faculty: Science

Abstract: Abstract Background and aim: Resveratrol (RSVL), a polyphenolic phytoestrogen in grapes, confers multifaceted cardiovascular benefits. The cellular and molecular basis of RSVL actions has been largely undefined until now. Methods and results: In human coronary smooth muscle cells (HCSMCs), RSVL markedly (3.2-fold) enhanced cGMP formation (t(1/2): 6.3 min, EC(50): 1.8 microM) and stimulated kinase-G activity (4-fold). By contrast, RSVL had no effect on cAMP or PKA activity in these cells. The RSVL-enhanced cGMP/kinase-G activity was not abrogated by the nitric oxide synthase-inhibitor (L-NMMA, 10 microM), or the soluble guanylyl cyclase (sGC)-inhibitor (ODQ, 10 microM). In membrane preparations from HCSMCs, RSVL activated GC in the particulate-, but not in the soluble-membrane fraction. Similar effects were due to the specific particulate-GC-A agonist atrial natriuretic peptide (ANP, 0.1-1 microM). The combined effects of RSVL and ANP were competitive. By contrast, the selective GC-B agonist (BNP) showed no response on cGMP, whereas that for GC-C (guanylin) produced only slight increases in cGMP levels. Estradiol (E2) mimicked the effects of RSVL on cGMP, but showed a 46% lower maximal response. Combining E2 with RSVL showed a competitive, rather than an additive, response. Further, cGMP formation by RSVL or E2 was significantly attenuated by the pure estrogen receptor blocker, ICI-182,780 (10 microM). Conclusion: These findings are the first to link RSVL with pGC/kinase-G activation downstream from membrane ERs in the vasculature, thus substantiating its coronary protective effects, even in endothelium-disrupted coronary arteries.

Keywords: Resveratrol, Coronary smooth muscle cells, soluble guanylyl cyclase

Research Title: Potent antiproliferative effects of Resveratrol on human osteosarcoma SJSA1 cells: Novel cellular mechanisms involving ERKs/p53 cascade.

Author: Sahar Majdi Jaffal, Published Year: 2006

Free Radicle Biology of Medicine , 41: 318-325.

Faculty: Science

Abstract: The chemopreventive activity of resveratrol (RSVL) has been demonstrated in several types of cancer. However, its effects and the underling mechanisms remain poorly understood. In this study, we investigated the involvement of the mitogen activated protein kinase (MAPK)/p53 signal transduction mechanism in RSVL-induced growth inhibition using a human osteosarcoma cell line. We demonstrate that RSVL reduces cell viability and growth of SJSA1 osteosarcoma cells. Morphological profiles and 4,6-diamidino-2-phenylindole nuclear staining of RSVL-treated cells indicated marked nuclear fragmentation. Cleavage of the (116-kDa) poly(ADP-ribose) polymerase protein into an 89-kDa fragment (a proapoptotic marker system) was substantially augmented by RSVL treatment. RSVL-dependent growth impairment was preceded by enhanced phosphorylation of extracellular signal-regulated kinase (ERK)1/2 (at Thr202/Tyr204). Likewise, RSVL increased the phosphorylation of p53 tumor suppressor protein (at Ser15). The effects of RSVL on ERKs and on p53 phosphorylation were abrogated by either the MAPK inhibitor PD98059 or the p53 inhibitor pifithrine-α. The present study indicates that RSVL antiproliferative effects on osteosarcoma cells are mediated by the activation of the ERKs/p53 signaling pathway and therefore identifies new targets for strategies to treat and/or prevent osteosarcoma.

Keywords: Resveratrol, cancer, osteosarcoma SJSA1 cells

Research Title: Effects of Meloxicam on Implantation and Parturition of Rat.

Author: Sahar Majdi Jaffal, Published Year: 2006

Jordan Medical Journal , 40 (2): 88-95.

Faculty: Science

Abstract: Meloxicam, a selective cyclooxygenase-2 preferential inhibitor, was studied for its anti-implantation and parturition effects on pregnant rats. Regarding the effect of meloxicam on implantation, rats were dosed orally by 7.5 and 10 mg/kg/day from day 1 through 3 or from day 3 through 5 of gestation, respectively. While for the parturition effect, rats were dosed orally by the above doses from day 20 through 22 of gestation. The results of implantation experiments showed that the number of implantation sites was significantly decreased in all treated groups in a dose- and time-dependent manner. Whereas the number of resorption sites were significantly increased in all meloxicam treated groups. On the other hand, the results of parturition experiments indicated that meloxicam significantly prolonged the duration time of delivery in a dose-dependent manner. Further, significantly less viable fetuses and pups were delivered per female treated with meloxicam. In conclusion, the results indicate that meloxicam exhibited potential effect on implantation and parturition processes of pregnant rats.

Keywords: Meloxicam, Implantation, Parturition

Research Title: Nerve growth factor enhances cough and airway obstruction via TrkA and TRPV1 receptor-dependent mechanisms

Author: Sahar Majdi Jaffal, Published Year: 2009

Thorax, 64 (9): 791-797.

Faculty: Science

Abstract: Background: Nerve growth factor (NGF) is an important mediator of airway hyper-responsiveness and hyperalgesia but its role in cough is unknown. Objectives: In this study the effects of NGF on the cough reflex and airway calibre were investigated in guinea pigs. The involvement of the tropomyosin-related kinase A (TrkA) receptor and transient receptor potential vanilloid-1 (TRPV1), and the p38 mitogen-activated protein kinase (MAPK)-dependent pathway in any NGF-induced effects on cough and airway obstruction was also assessed. Methods: Guinea pigs were placed in a transparent whole-body plethysmograph box. Cough was assessed visually, acoustically and by analysis of the airflow signal. Airway obstruction was measured using enhanced pause (Penh) as an index. Results: Exposure of guinea pigs to NGF did not induce a cough response nor a significant airway obstruction. However, exposure of guinea pigs to NGF immediately before citric acid inhalation resulted in a significant increase in the citric acid-induced cough and airway obstruction compared with vehicle-treated animals. Pretreatment with the TrkA receptor antagonist, K252a, or the TRPV1 antagonist, iodoresiniferatoxin, significantly inhibited the NGF-enhanced cough and airway obstruction. Exposure to NGF also increased p38 MAPK phosphorylation, but pretreatment with the p38 MAPK inhibitor, SB203580, did not affect either the NGF-enhanced cough or airway obstruction despite preventing the NGF-induced elevation in p38 MAPK phosphorylation. Conclusions: The data show that NGF can enhance both cough and airway obstruction via a mechanism that involves the activation of the TrkA receptor and TRPV1 but not the p38 MAPK-dependent pathway.

Keywords: Cough, airway obstruction, NGF, TRPV1

Research Title: Effect of inhibition of the ubiquitin-proteasome-system and IκB kinase on airway inflammation and hyperresponsiveness in a murine model of asthma.

Author: Sahar Majdi Jaffal, Published Year: 2011

International Journal of Immunopathology and Pharmacology , 24 (1): 33-42.

Faculty: Science

Abstract: The current treatment of asthma is far from optimal and there is a need for novel therapeutic approaches. NFkB has recently been highlighted as an important pro-inflammatory transcriptional factor and its blockade is believed to represent a new therapeutic approach for asthma. The purpose of this study is to investigate the effects of blocking the actions of NFkB, through inhibition of the ubiquitin-proteasome system (UPS) or IkB kinase (IKK), in a murine model of asthma. Treatment with the UPS inhibitor, MG-132 (0.03 and 0.1 mg/kg), did not significantly affect the ovalbumin-induced increase in total and differential cell numbers, histological changes such as perivascular and peribronchial inflammatory cell infiltration, perivascular and peribronchial fibrosis or the increased Penh to methacholine. In contrast, treatment of mice with the IKK inhibitor, BAY 11-7085, (3 and 10 mg/kg) dose-dependently inhibited the ovalbumin-induced increase in airway leukocyte influx and decreased the percentage of airway lymphocytes, neutrophils and eosinophils. Also, BAY 11-7085-treated (10 mg/kg) mice showed a significant decrease in the histologically assessed inflammatory indices as well as a significant reduction in the ovalbumin-induced increase in Penh to inhaled methacholine. Furthermore, BAY 11-7085 significantly inhibited the ovalbumin-induced increase in the level of phosphorylation of IkBalpha and extracellular regulated kinases (ERK) 1/2, whilst MG-132 significantly increased the phosphorylation of (ERK) 1/2. These findings confirm the critical role that NFkB plays in airway inflammation, highlight the importance of IKK in regulating the pro-inflammatory activity of NFkB and also suggest that UPS may not be a useful drug target for asthma treatment.

Keywords: ubiquitin-proteasome system (UPS), inflammation, hyperalgesia

Research Title: Anti-tussive and bronchodilator mechanisms of action for the enaminone E121.

Author: Sahar Majdi Jaffal, Published Year: 2011

Life Science , 89 (11-12): 378-387.

Faculty: Science

Abstract: Abstract Aims: In this study, we investigated whether the enaminone, E121, has anti-tussive effects in a guinea pig model of cough, and if so, whether this effect is mediated via a central or peripheral site of action. We also assessed whether E121 has bronchodilator effects and the molecular mechanisms underlying any anti-tussive and/or bronchodilator effects. Main methods: Whole body plethysmography was used to assess both cough and airway obstruction. A stereotaxic apparatus was used to administer drugs intracerebroventricularly (i.c.v.). Effects of E121 were examined in vitro on contractile effects in guinea pig bronchioles. Key findings: Pre-treatment of animals with E121 resulted in a significant inhibition in the citric acid-induced cough and airway obstruction compared to vehicle-pretreated animals. The K(ATP) antagonist, glibenclamide, significantly inhibited the anti-tussive and bronchoprotective effects of E121. Also, intra-tracheal administration of E121 resulted in a significant inhibition of both the citric acid-induced cough response and airway obstruction compared to vehicle-pretreated animals. By contrast, i.c.v. administration had no effect. Finally, E121 significantly inhibited carbachol-induced airway smooth muscle contractions, an effect that was reduced by both glibenclamide and propranolol. Interestingly, E121 enhanced histamine-induced cAMP release in human eosinophils although it did not directly elevate cAMP levels. Significance: The enaminone, E121, has anti-tussive and bronchodilatory effects and is topically, but not centrally, active. The anti-tussive mechanism of action of E121 seems to be K(ATP) channel dependent, whereas its bronchodilatory effects appear to be mediated via activation of both K(ATP) channels and β(2) receptors. Therefore, E121 may potentially represent a novel therapy for cough, particularly cough associated with airway obstruction.

Keywords: Cough, bronchodilation, enaminone

Research Title: Biasing the prostaglandin F2α receptor responses toward EGFR-dependent transactivation of MAPK.

Author: Sahar Majdi Jaffal, Published Year: 2012

Molecular Endocrinology, 26(7): 1189-1202.

Faculty: Science

Abstract: The G protein-coupled prostaglandin F2α (PGF2α) receptor [F prostanoid (FP) receptor] has been implicated in many physiological events including cardiovascular, respiratory, immune, reproductive, and endocrine responses. Binding of PGF2α to FP receptor elicits inositol production and protein kinase C-dependent MAPK activation through Gαq coupling. Here we report that AL-8810, previously characterized as an orthosteric antagonist of PGF2α-dependent, Gαq-mediated signaling, potently activates ERK1/2 in a protein kinase C-independent manner. Rather, AL-8810 promoted ERK1/2 activation via an epidermal growth factor receptor transactivation mechanism in both human embryonic kidney 293 cells and in the MG-63 osteoblast-like cells, which express endogenous FP receptors. Neither AL-8810- nor PGF2α-mediated stimulation of FP receptor promoted association with β-arrestins, suggesting that MAPK activation induced by these ligands is independent of β-arrestin's signaling scaffold functions. Interestingly, the spatiotemporal activation of ERK1/2 promoted by AL-8810 and PGF2α showed almost completely opposite responses in the nucleus and the cytosol. Finally, using [3H]thymidine incorporation, we noted differential regulation of PGF2α- and AL-8810-induced cell proliferation in MG-63 cells. This study reveals, for the first time, the signaling biased nature of FP receptor orthosteric ligands toward MAPK signaling. Our findings on the specific patterns of ERK1/2 activation promoted by FP receptor ligands may help dissect the distinct roles of MAPK in FP receptor-dependent physiological responses.

Keywords: PGF2α, FP, EGFR, MAPK

Research Title: (2013). Nerve growth factor enhances cough via a central mechanism of action.

Author: Sahar Majdi Jaffal, Published Year: 2013

Pharmacological Research , 74: 68-77.

Faculty: Science

Abstract: Abstract The mechanisms involved in enhanced cough induced by central and inhaled NGF in guinea pigs were investigated. Cough and airway function were assessed by plethysmography following inhaled or intracerebroventricular (i.c.v.) NGF treatment. Expression of TrkA and/or TRPV1 was determined in bronchi and/or brainstem by real-time PCR and immunoblotting. I.c.v. and inhaled NGF enhanced citric acid induced-cough and airway obstruction. Pretreatment (i.c.v.) with antagonists of TrkA (K252a) or TRPV1 (IRTX) significantly reduced both the NGF (i.c.v.) enhanced cough and airway obstruction whereas the NK1 antagonist (FK888) inhibited only cough. The H1 antagonist (cetirizine) did not affect either. Inhaled NGF increased phosphorylation of TrkA receptors in the bronchi but not the brainstem at 0.5h post-treatment. TrkA mRNA was elevated at 0.5h in the bronchi and at 24h in the brainstem while TRPV1 mRNA was elevated from 0.5h to 24h in brainstem and at 24h in the bronchi. Pretreatment (i.c.v.) with IRTX, but not K252a, significantly inhibited the inhaled NGF-enhanced cough. Central NGF administration enhances cough and airway obstruction by mechanisms dependent on central activation of TrkA, TRPV1 and NK1 receptors while inhaled NGF enhances cough via a mechanism dependent on central TRPV1 and not TrkA receptors. These data show that NGF, in addition to its effects on the airways, has an important central mechanism of action in the enhancement of cough. Therefore, therapeutic strategies targeting NGF signaling in both the airways and CNS may be more effective in the management of cough.

Keywords: ACSF; ASCIC-3; AUC; BSA; CNS; Cough; H(1); I.c.v.; Inhalation; NGF; NK(1); NTS; PBS; TRPV1; TrkA; acid sensing ion channel 3 protein;