Wet Cupping Reduces Pain and Improves Health-related Quality of Life Among Patients with Migraine: A Prospective Observational Study

Objectives: To determine the benefits of wet cupping on pain and health-related quality of life (HRQOL) in adult patients with migraine headaches. Methods: We conducted a prospective observational study of wet cupping in 128 patients referred to the cupping clinic at King Abdulaziz University Hospital, Jeddah, Saudi Arabia between January 2013 and December 2015. Bloodletting was performed at the base of the head and between the shoulders monthly four times. We assessed migraine headache pain using the visual analog scale (VAS) and the quality of life of patients before and after each cupping session using the World Health Organization Quality of Life assessment instrument. Results: The mean age of the patients was 40.5±11.3 years with a preponderance of females (n = 114, 89.1%). VAS was averaged at 7 before the procedure and reduced to 3 after wet cupping, both during rest and activity (p ≤ 0.005). Ninety-five patients agreed to complete the quality of life questionnaire. There was a significant improvement in the quality of life after wet cupping treatment in most of the displayed items (p < 0.050). None of the patients reported post-procedure complications. Conclusions: Wet cupping might be considered a complementary treatment for migraine headache pain relief and improvement to a patient’s quality of life

Integrated Pangenome Analysis and Pharmacophore Modeling Revealed Potential Novel Inhibitors against Enterobacter xiangfangensis

Enterobacter xiangfangensis is a novel, multidrug-resistant pathogen belonging to the Enterobacter genus and has the ability to acquire resistance to multiple antibiotic classes. However, there is currently no registered E. xiangfangensis drug on the market that has been shown to be effective. Hence, there is an urgent need to identify novel therapeutic targets and effective treatments for E. xiangfangensis. In the current study, a bacterial pan genome analysis and subtractive proteomics approach was employed to the core proteomes of six strains of E. xiangfangensis using several bioinformatic tools, software, and servers. However, 2611 nonredundant proteins were predicted from the 21,720 core proteins of core proteome. Out of 2611 nonredundant proteins, 372 were obtained from Geptop2.0 as essential proteins. After the subtractive proteomics and subcellular localization analysis, only 133 proteins were found in cytoplasm. All cytoplasmic proteins were examined using BLASTp against the virulence factor database, which classifies 20 therapeutic targets as virulent. Out of these 20, 3 cytoplasmic proteins: ferric iron uptake transcriptional regulator (FUR), UDP-2,3diacylglucosamine diphosphatase (UDP), and lipid-A-disaccharide synthase (lpxB) were chosen as potential drug targets. These drug targets are important for bacterial survival, virulence, and growth and could be used as therapeutic targets. More than 2500 plant chemicals were used to molecularly dock these proteins. Furthermore, the lowest-binding energetic docked compounds were found. The top five hit compounds, Adenine, Mollugin, Xanthohumol C, Sakuranetin, and Toosendanin demonstrated optimum binding against all three target proteins. Furthermore, molecular dynamics simulations and MM/GBSA analyses validated the stability of ligand–protein complexes and revealed that these compounds could serve as potential E. xiangfangensis replication inhibitors. Consequently, this study marks a significant step forward in the creation of new and powerful drugs against E. xiangfangensis. Future studies should validate these targets experimentally to prove their function in E. xiangfangensis survival and virulence

Inhibition of proliferation and induction of apoptosis by thymoquinone via modulation of TGF family, P53, P21 and BCL-2α in leukemic cells

Introduction: Adult T-cell leukemia (ATL) is an aggressive form of malignancy caused by human T-cell lymphotropic virus 1 (HTLV-1). Currently, there is no effective treatment for ATL. Thymoquinone has been reported to have anti-cancer properties. Objective: The aim of this study is to investigatthe effects of TQ on proliferation, apoptosis induction and the underlying mechanism of action in both HTLV-1 positive (C91-PL and HuT-102) and HTLV-1 negative (CEM and Jurkat) malignant T-lymphocytes. Materials and methods: Cells were incubated with different thymoquinone concentrations for 24h. Cell cytotoxicity was assayed using the CytoTox 96® Non-Radioactive Cytotoxicity Assay Kit. Cell proliferation was determined using CellTiter 96® Non-Radioactive Cell Proliferation. Cell cycle analysis was performed by staining with propidium iodide. Apoptosis was assessed using cell death ELISA kit. The effect of TQ on p53, p21, Bcl-2 protein expression was determined using Western blot analysis while TGF mRNA expression was determined by RT-PCR. Results: At non-cytotoxic concentrations of TQ, it resulted in the inhibition of proliferation in a dose dependent manner. Flow cytometric analysis revealed a shift in the cell cycle distribution to the PreG1 phase which is a marker of apoptosis. Also TQ increase DNA fragmentation. TQ mediated its anti-proliferative effect and apoptosis induction by an up-regulation of TGFβ1, p53 and p21 and a down-regulation of TGF-α and Bcl-2α. Conclusion: Thymoquinone presents antiproliferative and proapoptotic effects in ATL cells. For this reason, further research is required to investigate its possible application in the treatment of ATL. © 2018 Bentham Science Publishers

Molecular characterization of glucose-6-phosphate dehydrogenase deficiency in Jeddah, Kingdom of Saudi Arabia

International audienceABSTRACT: BACKGROUND: The development of polymerase chain reaction (PCR)-based methods for the detection of known mutations has facilitated detecting specific red blood cell (RBC) enzyme deficiencies. We carried out a study on glucose-6-phosphate dehydrogenase (G6PD) deficient subjects in Jeddah to evaluate the molecular characteristics of this enzyme deficiency and the frequency of nucleotide1311 and IVS-XI-93 polymorphisms in the glucose-6-phosphate dehydrogenase gene. RESULTS: A total of 1584 unrelated Saudis (984 neonates and 600 adults) were screened for glucose-6-phosphate dehydrogenase deficiency. The prevalence of glucose-6-phosphate dehydrogenase deficiency was 6.9% (n=110). G6PD Mediterranean mutation was observed in 98 (89.1%) cases, G6PD Aures in 11 (10.0%) cases, and G6PD Chatham in 1 (0.9%) case. None of the samples showed G6PD A mutation. Samples from 29 deficient subjects (25 males and 4 females) were examined for polymorphism. The association of two polymorphisms of exon/intron 11 (c.1311T/IVS XI 93C) was observed in 14 (42.4%) of 33 chromosomes studied. This association was found in 9 (31.0%) carriers of G6PD Mediterranean and in 4 (13.8%) carriers of G6PD Aures. CONCLUSIONS: The majority of mutations were G6PD Mediterranean, followed by G6PD Aures and <1% G6PD Chatham. We conclude that 1311T is a frequent polymorphism in subjects with G6PD Mediterranean and Aures variants in Jeddah

Diosgenin alleviates D-galactose-induced oxidative stress in rats’ brain and liver targeting aging and apoptotic marker genes

The theory of aging is primarily concerned with oxidative stress caused by an imbalance in reactive oxygen species generation and cellular antioxidants. To alleviate the oxidative stress, we investigated the protective effect of diosgenin (DSG) for D-galactose (D-gal) using 20 and 40 mg of DSG/kg/day/orally for 42 days. The findings showed that D-gal caused brain and liver oxidative injuries by upregulating aging and oxidative markers. To counteract the oxidative stress caused by D-gal, DSG upregulated glutathione peroxidase-1, superoxide dismutase-1, and glutathione S-transferase-α. DSG also diminished the expression of p53, p21, Bcl-2-associated X protein, caspase-3, and mammalian target of rapamycin in brain and liver, as well as the build-up of β-galactosidase. DSG, in a dose-dependent manner, decreased the oxidative aging effects of D-gal in brain and liver tissues through targeting of aging and apoptotic marker genes. Finally, it should be noted that consuming DSG supplements is a suggesting natural preventative agent that may counteract aging and preserve health through improvement of body antioxidant status and control aging associated inflammation and cellular apoptosis

Insight into the phytochemical profile and antimicrobial activities of Amomum subulatum and Amomum xanthioides: an in vitro and in silico study

IntroductionMedicinal plants have been considered as potential source of therapeutics or as starting materials in drugs formulation.MethodsThe current study aims to shed light on the therapeutic potential of the Amomum subulatom and Amomum xanthioides Fruits by analyzing the phytochemical composition of their seeds and fruits using gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) techniques to determine the presence of bioactive components such as flavonoids, phenols, vitamins, steroids, and essential oils.Results and DiscussionThe protein content is usually higher than the total lipids in both species except the fruit of A. subulatum which contain more lipids than proteins. The total protein contents for A. subulatum were 235.03 ± 21.49 and 227.49 ± 25.82 mg/g dry weight while for A. xanthioides were 201.9 ± 37.79 and 294.99 ± 37.93 mg/g dry weight for seeds and fruit, respectively. The Carvacrol levels in A. subulatum is 20 times higher than that in A. xanthioides. Lower levels of α-Thujene, Phyllanderenes, Ascaridole, and Pinocarvone were also observed in both species. According to DPPH (2,2-diphenylpicrylhydrazyl) assay, seed the extract of A. subulatum exhibited the highest antioxidant activity (78.26±9.27 %) followed by the seed extract of A. xanthioides (68.21±2.56 %). Similarly, FRAP (Ferric Reducing Antioxidant Power) assay showed that the highest antioxidant activity was exhibited by the seed extract of the two species; 20.14±1.11 and 21.18±1.04 µmol trolox g−1 DW for A. subulatum and A. xanthioides, respectively. In terms of anti-lipid peroxidation, relatively higher values were obtained for the fruit extract of A. subulatum (6.08±0.35) and the seed extract of A. xanthioides (6.11±0.55). Ethanolic seed extracts of A. subulatum had the highest efficiency against four Gram-negative bacterial species which causes serious human diseases, namely Pseudomonas aeruginosa, Proteus vulgaris, Enterobacter aerogenes, and Salmonella typhimurium. In addition, P. aeruginosa was also inhibited by the fruit extract of both A. subulatum and A. xanthioides. For the seed extract of A. xanthioides, large inhibition zones were formed against P. vulgaris and the fungus Candida albicans. Finally, we have in silico explored the mode of action of these plants by performing detailed molecular modeling studies and showed that the antimicrobial activities of these plants could be attributed to the high binding affinity of their bioactive compounds to bind to the active sites of the sterol 14-alpha demethylase and the transcriptional regulator MvfR.ConclusionThese findings demonstrate the two species extracts possess high biological activities and therapeutical values, which increases their potential value in a number of therapeutic applications

Vermicompost Supply Modifies Chemical Composition and Improves Nutritive and Medicinal Properties of Date Palm Fruits From Saudi Arabia

To meet the increased demand for phytochemicals, plant cultivation in soil amended with biofertilizers has been developed. Here, we aimed to use vermicompost as an environmentally safe biofertilizer to enhance the nutritive and medicinal value of five common cultivars of Saudi date palm; namely Phoenix dactylifera L. var. Ajwa, Hulwa, Ruthana, Sefri, and Luban. To determine changes in the fruit nutritive composition, primary metabolites, antioxidants, phenolic compounds and mineral profiles were analyzed in the fruits from non-fertilized and vermicompost-fertilized date palms. We also tested how changes in the fruit chemical compositions due to vermicompost fertilization affected their medicinal potentials. Applying vermicomposts generally increased primary metabolites, vitamins, and mineral content as well as the medicinal potential of the date palm fruits. This positive effect is possibly explained by the role of vermicomposts in improving soil health and fertility. Furthermore, clustering analyses and principal component analysis (PCA) indicated cultivar-specific responses. PCA analysis also revealed that the bioactivities of the date palm fruit extracts and their antioxidants tended to display correlated output values. One of the highly accumulated phenolic compounds, β-D-glucogallin, was extracted and purified from P. dactylifera L. var. Ajwa fruits and showed significant antioxidant, anticancer, antibacterial, antimutagenic, and antiprotozoal activities. Overall, applying vermicompost is an innovative approach to increase the nutritive quality and medicinal potential of date palm fruits

Using Noval Experimental PM 701 in Refractory Hodgkin’s Disease Combined with conventional Therapy

Abstract Background: To the many profound changes we now face in health care, Complementary and Alternative Medicine (CAM) must be added as a major factor. There is evidence of the increasing use of CAM by patients diagnosed with cancer. Interest in CAM continues to grow at an exponential rate despite the advances made by conventional medicine. Given the increasing desire of cancer patients to use CAM, it is important that clinicians have a good understanding of the evidence available in this field and build a trust with their patients. Many oncologists are not familiar with CAM used by many of their patients. Aims: To report the effectiveness and safety of a natural experimental agent used with conventional therapy in a patient with Stage IV Hodgkin’s lymphoma refractory to treatment. Methods: An eight-years-old Saudi girl was diagnosed as Stage IV Hodgkin’s lymphoma with lung infiltration. The patient was started on chemotherapy (ABVD), and needed prolonged hospitalization due to weakness, loss of appetite, cachexia, dyspnea, cough, fever, and marked hepatosplenomegaly. She had six cycles of chemotherapy with a slight improvement in her general condition. However, she as considered refractory to conventional therapy. We were planning to refer her for bone marrow transplant. The patient was sent home to be readmitted for the seventh cycle of ABVD. Unfortunately, the patient’s general condition deteriorated and she was admitted to the Intensive Care Unit (ICU), with acute Respiratory Distress Syndrome (RDS). She was markedly unstable and required respiratory ventilation support. After discussions involving the parents, it was suggested to use an experimental natural remedy of proven efficacy in inducing apoptosis in tissue cultures and animals in our laboratories. On the fifth day in ICU, the patient was initiated with full dose ABVD combined with the natural remedy, classified as PM 701. Within 2 days, the patient became fully conscious, showed improved general condition and returned to the pediatric ward to continue her treatment. Results: After the seventh cycle of chemotherapy and the use of natural remedy, her general condition improved markedly with significant reduction of the hepatosplenomegaly and pleural effusions. Repeated CT scans of chest and abdomen showed marked regression of her disease. She had one more cycle of chemotherapy combined with PM 701 and assessment after the eighth cycle showed complete remission of her disease including in the lungs. This natural agent has been fully studied with animal models at the King Fahed Medical Research Center’s laboratory and showed potent selective apoptosis of cancer cells, effective and safe in animal models. Summary: Most childhood malignancy is curable with combined intensive conventional chemotherapy, however up to 30% may have relapse or be resistant to chemotherapy. We report in this case successful management with the combination of conventional therapy with experimental medicine (PM 701) in the treatment of refractory Hodgkin’s lymphoma, which needs further control studies in the future to prove the efficacy and safety to be used on oncology patients. Integration between chemotherapy and natural CAM should be under close supervision to ensure safety and effectiveness. Scientific research needs more effort to support this line of medicine.</jats:p

Successful Management of Refractory Severe Thrombocytopenia Associated with Antiphospholipid Syndrome Using rituximab

Abstract Background: Rituximab, a monoclonal antibody against the pan B-cell antigen CD20, that induces a rapid in vivo depletions of normal B lymphocytes. Although this agent was originally developed for use in patients with B-cell-NHL, its use has been successfully extended to many autoimmune disorders. Thrombocytopenia associated with antiphospholipid syndrome can be mild to severe. Severe cases can be associated with significant morbidity and mortality if refractory to the usual therapy for autoimmune thrombocytopenia. Aim: To report an effective regimen in treating a case of severe bleeding thrombocytopenia associated with antiphospholipid syndrome. Patient and Methods: A 49 year old female was diagnosed with thrombocytopenia associated with antiphospholipid syndrome and antibodies to double-stranded DNA, controlled over the last 15 years. Unfortunately, over the last two years the patient has had frequent admissions for uncontrolled nose bleed, soft palate petechiae and generalized bruising. Many treatments have been tried for this case of difficult refractory bleeding with platelets in the range 2.0–6.0 K/uL. These include systemic treatments such as corticosteroids, high pulse therapy of methylprednisolone, Imuran, i.v. immunoglobulin infusion and anti Rh-D intravenous therapy. We report an adult female patient with severe refractory bleeding thrombocytopenia associated with antiphospholipid syndrome and successful treatment with Rituximab. Her platelets count have been maintained above 200.0K/uL over a 14 months period. Unfortunately, this patient has had side effects of steroid therapy. In conclusion: Rituximab may be effective treatment on patients with refractory, severe thrombocytopenia associated with antiphospholipid syndrome and significant bleeding complications. Rituximab is a promising alternative option for the eradication of the autoantibodies and restoration of normal hemostasis while avoiding the use of high-dose steroid in refractory bleeding thrombocytopenia.</jats:p

Survival and Disease Complication of Thalassemia Major: Experience of 14 Years at King Abdulaziz University Hospital, Jeddah, KSA

Treatment of thalassemia major is complex, expensive and requires a multidisciplinary approach. Optimal clinical care is demanding and expensive, but achievable. To assess the prevalence of survival and disease complications among patients with thalassemia major treated at our center; a retrospective chart review was done of all patients followed and treated at King Abdulaziz University Hospital with a diagnosis of Thalassemia Major from 1990-2004. A total of 360 patients (203 males &amp; 157 females) were transfusion dependant since early childhood and treated with parenteral Deferoxamine. Out of 360 patients, 293 (90.29%) patients were alive, 27 (7.2%) patients had died, 15 (4.2%) patients underwent BMT and 25 (6.9%) patients'follow-up were lost. Twelve (3.3%) patients died from heart disease. 7 (1.9%) patients died from infections, all patients were splenectomized. The serum ferritin levels for patients who died were significantly higher than for those patients who survived (7,500 vs. 3, 200; p &lt; 0.001). Cardiac constitutes the first important cause of death followed by infection. Complications and deaths among thalassemics is iron related organ dysfunction and age related. The majority of complicated patients were on non-optimal chelation therapy and non-compliance.</jats:p