The relationship between coping self-efficacy and B cells in breast cancer patients.

BACKGROUND: Breast cancer is the most common tumor among women throughout the world. Diagnosis and treatment of breast cancer are associated with stress and depression. Self-efficacy is one of the most important personal characteristics, studied in cancer, and is correlated with depression and immunity. The aim of the study is as follows: 1. Examining the correlation between coping self-efficacy with depression, DHEA levels, and immunity 2. Examining the correlation between depression and DHEA levels 3. Studying the effect of depression and DHEA levels on immunity 4. Examining the intermediate effect of DHEA levels on the correlation between coping self-efficacy and immunity METHODS: Thirty newly diagnosed breast cancer patients recruited from the Oncology Department, Kasr EL-Aini, Cairo University (ages 51.40 + 8.24 years) responded to two questionnaires: Coping Self-Efficacy Scale (CSES) and Patient Health Questionnaire-9 (PHQ-9); blood samples were collected to measure the phenotype of patients' cellular immunity and DHEA levels by flowcytometry and ELISA technique. RESULTS: There was a significant negative correlation between CSES and PHQ-9, a significant positive correlation between PHQ-9 and B-cell count, and there is a significant negative correlation between CSES and B-cell count. The presence of DHEA has no mediatory role on correlation between CSES and B-cell count. CONCLUSION: This paper presents a new model of psychoneuroimmunology by suggesting an effect of coping self-efficacy on immunity against breast cancer patients.

Bee venom as an alternative for antibiotics against Staphylococcus aureus infections.

The misuse of antibiotics has led to antibiotic-resistant bacterial strains, making it even harder to combat and eliminate their infections. Staphylococcus aureus causes various adverse infections and diseases, including skin abscesses, bloodstream infections, pneumonia, and joint infections. In this study, we aimed to test the cytotoxic and antibacterial effects of bee venom-loaded chitosan nanoparticles (BV-loaded CS-NPs) in comparison to gamma-irradiated BV and native BV from Apis mellifera. The physiochemical characterizations of our treatments were determined by Fourier Transform Infrared Spectroscopy (FTIR), Transmission Electron Microscope (TEM), zeta-potential, release rate, and Encapsulation Efficiency (EE). Our study was conducted on both levels, in-vitro and in-vivo. For the in-vitro study, a bacterial model of Staphylococcus aureus with an ATCC number of 6538 was grown in tryptic soy agar (TSA) medium, and the inhibition zones of our drug candidates were measured with the appropriate statistical analysis performed. For the in-vivo study, levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), Creatinine, Urea, and interleukin 6 (IL-6) were analyzed. BV-loaded CS-NPs showed relatively better results than the other alternatives, which are native BV and gamma-irradiated BV. The results showed that the antibacterial effect of BV-loaded CS-NPs was greater than the alternatives. Furthermore, its cytotoxic effect was far less than the native and irradiated bee venom. These outcomes ensure that loading BV on CS-NPs makes it a promising drug candidate for an antibiotic alternative with minimal cytotoxicity and enhanced antibacterial activity.

B-cell activating factor and A proliferation-inducing ligand in relation to intima-media thickness as biomarkers of premature atherosclerosis in systemic lupus erythematosus patients.

BACKGROUND: The aim of this study was to assess the correlation of the serum B-cell activating factor (BAFF), A proliferation-inducing ligand (APRIL) and interleukin (IL)-21 with carotid intima-media thickness (cIMT) to evaluate their efficacy as non-invasive biomarkers for the risk of premature development of atherosclerosis. METHODS: ELISA test was used to quantify serum BAFF, APRIL and IL-21 in 40 patients with systemic lupus erythematosus (SLE) and 20 healthy controls (HCs). The obtained results were correlated with disease duration, anti-double stranded DNA, complement proteins levels, lipid profile, cIMT and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). RESULTS: Serum BAFF, APRIL and IL-21 were significantly increased in SLE compared to HCs. Positive correlation was recorded between BAFF (r = 0.51) and APRIL (r = 0.52) with the cIMT. IL-21 correlated positively with SLEDAI (r = 0.33) and negatively with BAFF (r = -0.37) and APRIL (r = -0.44). According to the multiple logistic regression analysis, we found that low-density lipoprotein, serum BAFF and APRIL values were independent factors for cIMT in SLE. To discriminate premature atherosclerosis in patients with SLE, BAFF ≥455 pg/ml yielded 88.9% sensitivity with 100% specificity while APRIL ≥600 pg/ml yielded 95% sensitivity with 100% specificity. IL-21 ≥240 pg/ml yielded 66.7% sensitivity and 100% specificity. CONCLUSIONS: Circulating BAFF and APRIL in patients with SLE were correlated to disease activity and cIMT, suggesting that they could be used as a peripheral blood biomarker for the occurrence of premature atherosclerosis in SLE.

In vitro and in vivo impacts of nifedipine and diltiazem on praziquantel chemotherapy in murine Schistosoma mansoni.

AIM: This study was planned to evaluate the in vitro and in vivo antischistosomal effects of the widely used antihypertensive drugs, nifedipine (NIF) and diltiazem (DTZ), and their combinations with praziquantel (PZQ) on early and late Schistosoma (S.) mansoni infections 21- and 45- days old stages. METHODS: In the In vitro study, Calcium channel blockers (CCBs), NIF and DTZ were added to schistosomula and adult worm cultures in different concentrations 10, 20 and 30 mg/ml. The mortality percentage was calculated 1, 12 and 24 h after incubation. In vivo, NIF and DTZ either alone or combined with PZQ were used to treat male albino mice. The parasitological and total immunoglobulin (Ig) G and IgM anti-soluble egg antigen (SEA) were assessed to demonstrate the disease severity. RESULTS: In the In vitro study, 10 mg/ml NIF induced 100% mortality percentage of both schistosomula and adult worms after 24 h incubation, while DTZ induced similar mortality percentage at 30 mg/ml concentration. In vivo results showed that early or late combination of 30 mg/kg of NIF, but not DTZ, significantly (P <0.05) enhanced the reductive efficacy of PZQ based on the parasitological data. The maximal reduction (P <0.05) of anti-SEA IgM and IgG levels was developed during NIF-PZQ administration 21- (1.12 ± 0.06 and 1.09 ± 0.04, respectively) or 45- (1.00 ± 0.03 and 0.8 ± 0.06, respectively) days post infection (PI), compared to either PZQ or NIF individual treatments. The decreased concentration of anti-SEA antibodies was correlated with the diminished granulomatous diameter and disease severity. CONCLUSION: Nifedipine improved PZQ chemotherapy targeting either early or late S. mansoni infection in mice compared to the PZQ mono-therapy. Administering NIF can be considered as a promising drug candidate for schistosomiasis chemotherapy.

The potential use of serum interleukin-21 as biomarker for lupus nephritis activity compared to cytokines of the tumor necrosis factor (TNF) family.

OBJECTIVE: Lupus nephritis (LN) is a significant consequence of systemic lupus erythematosus (SLE). To the best of our knowledge, this is the first work that focuses on evaluation of serum interleukin (IL-) 21 as a diagnostic biomarker of LN activity, compared to B lymphocyte stimulator (BlyS), tumor necrosis factor ligand superfamily member 13 (TNF-SF13), and traditional techniques of active LN attempting to compare their diagnostic usefulness. METHODS: Serum levels of IL-21, BlyS, and TNF-SF13 during LN were investigated. Twenty-five biopsy-proven, active LN female patients and 15 SLE patients without active LN and 20 healthy controls (HCs) joined this work. RESULTS: Serum IL-21 level was significantly higher in active LN group than in inactive LN group. Correlation analysis showed that serum IL-21 levels were significantly correlated with total SLEDAI (r = 0.41, p = 0.03), renal-SLEDAI (r = 0.48, p = 0.04), renal activity index (AI) (r = 0.93; p < 0.001), and 24-h proteinuria (r = 0.51; p > 0.008). Receiver operating characteristic curve (ROC) revealed the ability of serum IL-21 to discriminate between active and inactive LN with 70% sensitivity at >240 pg/ml cutoff point (AUC 0.809). CONCLUSION: For Egyptian SLE patients, serum levels of IL-21 were superior to TNF-SF13 and BlyS and correlated significantly with the activity indexes of LN, indicating a promising role as a potential biomarker of active LN.

Encapsulation of Low Metronidazole Dose in Poly (D,L-lactide-co-glycolide) (PLGA) Nanoparticles Improves Giardia intestinalis Treatment.

BACKGROUND: The present study was designed to investigate the antigiardial efficacy of low metronidazole dose loaded-D.L-lactide-co-glycolide (LMD-PLGA) nanoparticles (NPs) and to compare it with the standard high dose of metronidazole either free (HMD) or loaded on PLGA (HMD-PLGA). MATERIALS AND METHODS: PLGA NPs were prepared by single emulsification method, metronidazole (MTZ) was loaded in low and high doses. The nanoparticles were evaluated in vivo for mice model. The Giardia intestinalis infected mice were treated by LMD and HMD either free or PLGA NPs loaded, the parasitic load and ployclonal antigiardial serum antibodies (IgG and IgA) were recorded. Histopathological studies on intestinal and liver sections were applied. RESULTS: MTZ-PLGA NPs was successfully prepared with 81.68% encapsulation efficiency and with an average particle size of approximately 228.00 ± 43.19 nm and -32.28 ± 0.07 mV Zeta potential. Experimentally, it was observed that Giardia intestinalis infected animals administered with LMD-PLGA had completely eliminated cyst shedding and trophozoite count compared with Giardia-infected mice. Further, it was found that animals belonging to LMD-PLGA group had significantly reduced levels of antigiardial IgA (0.99 ± 0.05) antibodies in serum compared with Giardia-infected. Histopathologyically, also animals belonging to LMD-PLGA treated group had intact mucosal epithelium lining, and normal villi with no detection of G. intestinalis trophozoites. In addition to the less toxic effect on the liver tissue compared to free HMD, HMD-PLGA and infected-untreated groups using Ishak grading system. CONCLUSION: Our study showed that PLGA nanoparticles could be atrial delivery systems for antigiardial drugs to improve their therapeutic efficacy and minimize their side effects that results from frequent dosing.

Correlations between MHLC scores and Indicators of Immune Response in Egyptian Women with Breast Cancer.

BACKGROUND: Recent studies indicate the immune dysfunction in cancer patients in comparison with healthy individuals. The quality and quantity of this dysfunction are not equal in all patients even with similar cancer type. AIM: This study aims to correlate health locus of control (HLC) beliefs with CD4+ helper T (Thelper) cells, T regulatory (Treg) cells, NK cells, IL-1ß and TNF-a in breast cancer patients. PATIENTS AND METHODS: The study included 30 early diagnostic breast cancer patients who responded to Form C of the MHLC questionnaire that assessed internal (IHLC), chance (CHLC), doctor (DHLC) and other person's (OHLC) control of the patient's health status. Peripheral blood samples were collected to analyze the numbers and phenotype of Thelper cells, Treg cells and NK cells by flow cytometry and to measure gene expression of IL-1ß and TNF-a with real time PCR. RESULTS: A significant positive correlation was found between IHLC with Thelper cells and NK cells. However, a significant inverse correlation was found between DHLC with NK, Thelper and Treg cells. CONCLUSION: There is strong probability that the quality of immunity in cancer patients is related to their MHLC beliefs. Further research is recommended for studying whether MHLC beliefs of patients with other types of cancer can improve their immune responses and how beliefs control immune system.

Genistein Loaded Nanofibers Protect Spinal Cord Tissue Following Experimental Injury in Rats.

Innovative drug-delivery systems offer a unique approach to effectively provide therapeutic drug dose over the needed time to achieve better tissue protection and enhanced recovery. The hypothesis of the current study was to test the antioxidant and anti-inflammatory effects of genistein and nanofibers on the spinal cord tissue following experimental spinal cord injury (SCI). Rats were treated post SCI with genistein that is loaded on chitosan/polyvinyl alcohol (CS/PVA) nanofibers as an implantable drug-delivery system. SCI caused marked oxidative damage and inflammation, as is evident by the reduction in the super oxide dismutase (SOD) activity and the level of interleukin-10 (IL-10) in injured spinal cord tissue, as well as the significant increase in the levels of nitric oxide (NO), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-α). Treatment of rats post SCI with genistein and CS/PVA nanofibers improved most of the above-mentioned biochemical parameters and shifted them toward the control group values. Genistein induced an increase in the activity of SOD and the level of IL-10, while causing a decrease in NO, MDA, and TNF-α in injured spinal cord tissue. Genistein and CS/PVA nanofibers provide a novel combination for treating inflammatory nervous tissue conditions, especially when combined as an implantable drug-delivery system.

Diagnostic accuracy of serum miR-122 and miR-199a in women with endometriosis.

OBJECTIVE: To evaluate the value of serum microRNA-122 (miR-122) and miR-199a as reliable noninvasive biomarkers in the diagnosis of endometriosis. METHODS: During 2015-2016, at a teaching hospital in Egypt, a prospective cohort study was conducted on 45 women with pelvic endometriosis and 35 women who underwent laparoscopy for pelvic pain but were not diagnosed with endometriosis. Blood and peritoneal fluid (PF) samples were collected; interleukin-6 (IL-6) was detected by enzyme-linked immunosorbent assay and miR-122 and miR-199a expression was measured by quantitative real-time polymerase chain reaction. RESULTS: The serum and PF levels of IL-6, miR-122, and miR-199a were significantly higher in women with endometriosis than in controls (P<0.001 for all comparisons). Serum miR-122 expression was positively correlated with serum IL-6 (r=0.597), PF IL-6 (r=0.603), PF miR-122 (r=0.934), serum miR-199a (r=0.727), and PF miR-199a (r=0.653). Serum miR-199a expression was positively correlated with serum IL-6 (r=0.677), PF IL-6 (r=0.678), PF miR-122 (r=0.744), and PF miR-199a (r=0.932). Serum miR-122 and miR-199a had a sensitivity of 95.6% and 100.0%, and a specificity of 91.4% and 100%, respectively, for the detection of endometriosis. CONCLUSION: Serum miR-122 and miR-199a were significantly increased in endometriosis, indicating that these microRNAs might serve as biomarkers for the diagnosis of endometriosis.

IMMUNE-MOLECULAR IDENTIFICATION OF GIARDIA INTESTINALIS IN DIARRHOEAL CHILDREN: COMPARISON OF THREE DIAGNOSTIC METHODS.

Giardiasis is a major health problem in both developed and developing world. A variety of methods for diagnosis of Giardia duodenalis cysts or trophozoites is available but still has certain limitations. 100 sample from diarrhoeal children who attending outpatient clinic in Abu El Rish hospital, .Kasr Al Ainy, Faculty of Medicine, Cairo University, Egypt. Giardiasis was diagnosed by direct wet mount, microscopy after formal- ethyl acetate concentration, Ridascreen ELISA assay and n-PCR targeting beta giardin (bg) gene. Using ELISA as reference standard, the methods' sensitivities, specificities, positive (PPV) and negative (NPV) predictive values and positive (LR+) and negative (LR-) likelihood ratios with 95% confidence interval (95% CI) were analyzed.The diagnostic methods were evaluated to determine their impact on the posttest probability using Fagan's nomogram. All the studied methods led to a LR+ higher than 10 indicating ability to ruling in giardiasis. n-PCR recorded LR- equal 0.00 and the probability of giardiasis would be 0% if the test was negative. The methods were also ranked on basis of Multiattribute utility theory and Analytical hierarchy process with ELISA ranked better than n-PCR.

Effect of artemether on cytokine profile and egg induced pathology in murine schistosomiasis mansoni.

Artemether (ART), the methylated derivative of artemisinin, is an efficacious antimalarial drug that also displays antischistosomal properties. This study was designed to evaluate the immunomodulatory action of a single intramuscular dose (50 mg/kg body weight) of ART in comparison with PZQ treatment (42 days PI). ART administration was 7, 14, 21 and 45 days PI. ART effect was studied parasitologically, histopathologically and immunologically. It was found that maximum effect was reached when ART treatment interfered with 14 or 21 days old schistosomula. ART treatment 14 or 21 days PI was associated with shift from Th2 to Th1 predominancy (decrease in IL-4 and upgrading of serum IFN-γ levels). In conclusion, ART is a promising drug in control of schistosomiasis mansoni due to its reductive effect on worm burden and its role in improvement of hepatic granulomatous lesions.

Infection of Female BWF1 Lupus Mice with Malaria Parasite Attenuates B Cell Autoreactivity by Modulating the CXCL12/CXCR4 Axis and Its Downstream Signals PI3K/AKT, NFκB and ERK.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by abnormal autoreactivity in B cells. Lymphocytes and their soluble mediators contribute to the disease pathogenesis. We recently demonstrated that infecting lupus mice with malaria confers protection against lupus nephritis by attenuating oxidative stress in both liver and kidney tissues. In the current study, we further investigated B cell autoreactivity in female BWF1 lupus mice after infection with either live or gamma-irradiated malaria, using ELISA, flow cytometry and Western blot analysis. The lupus mice exhibited a significant elevation in plasma levels of IL-4, IL-6, IL-7, IL-12, IL-17, IFN-α, IFN-γ, TGF-ß, BAFF and APRIL and a marked elevation of IgG2a, IgG3 and ant-dsDNA autoantibodies compared with normal healthy mice. Infecting lupus mice with live but not gamma-irradiated malaria parasite partially and significantly restored the levels of the soluble mediators that contribute to the progression of lupus. Furthermore, the B cells of lupus mice exhibited an increased proliferative capacity; aberrant overexpression of the chemokine receptor CXCR4; and a marked elevation in responsiveness to their cognate ligand (CXCL12) via aberrant activation of the PI3K/AKT, NFκB and ERK signaling pathways. Interestingly, infecting lupus mice with live but not gamma-irradiated malaria parasite restored a normal proliferative capacity, surface expression of CXCR4 and B cell response to CXCL-12. Taken together, our data present interesting findings that clarify, for the first time, the molecular mechanisms of how infection of lupus mice with malaria parasite controls B cell autoreactivity and thus confers protection against lupus severity.

Novel IMB-ELISA Assay for Rapid Diagnosis of Human Toxoplasmosis Using SAG1 Antigen.

Nanotechnology is important for medical diagnosis. Various nanoparticles have presented tremendous potential for diagnosing disease markers, pre-cancerous cells, fragment of viruses, specific proteins, antibodies, and other disease indicators. In general, nanoparticles are smaller than 1,000 nm and produced from different materials in different shapes such as spheres, rods, wires, and tubes. Our study aimed to develop a novel antigen-capture immunoassay based on IgG polyclonal antibody-coated magnetic microbead nanoparticles for the rapid detection of circulating surface antigen 1 of Toxoplasma gondii in human serum samples. Sandwich ELISA elicited a sensitivity of 92%, a specificity of 92.7%, a positive predictive value (PPV) of 92%, and a negative predictive value (NPV) of 92.7%. Immunomagnetic bead-ELISA showed sensitivity (98%), specificity (96.4%), PPV (96%), and NPV (98.1%) higher than that of sandwich ELISA. It is obvious that the use of magnetic microbead nanoparticles offers the potential advantage of improving the diagnostic testing of toxoplasmosis.

Efficacy and safety of arachidonic acid for treatment of Schistosoma mansoni-infected children in Menoufiya, Egypt.

Arachidonic acid (ARA), an omega-6 fatty acid, kills juvenile and adult schistosomes in vitro and displays highly significant and safe therapeutic effects in mice and hamsters infected with Schistosoma mansoni or S. haematobium. This study aims to examine the efficacy and safety of ARA in treatment of school-age children infected with S. mansoni. In total, 66 S. mansoni-infected schoolchildren (20-23 children/study arm) received a single dose of 40 mg/kg praziquantel (PZQ), ARA (10 mg/kg per day for 15 days), or PZQ combined with ARA. The children were examined before and after treatment for worm egg counts in stool and blood biochemical and immunological parameters. ARA proved to be as efficacious as PZQ in treatment of schoolchildren with low infection intensity (78% and 85% cure rates, respectively). For moderate-intensity infection, the ARA and PZQ combination led to 100% cure rate. Biochemical, hematological, and immunological parameters were either unchanged or ameliorated after ARA therapy.

Malarial infection of female BWF1 lupus mice alters the redox state in kidney and liver tissues and confers protection against lupus nephritis.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by an imbalanced redox state and increased apoptosis. Tropical infections, particularly malaria, may confer protection against SLE. Oxidative stress is a hallmark of SLE. We have measured changes in the levels of nitric oxide (NO), hydrogen peroxide (H2O2), malondialdehyde (MDA), and reduced glutathione (GSH) in both kidney and liver tissues of female BWF1 lupus mice, an experimental model of SLE, after infection with either live or gamma-irradiated malaria. We observed a decrease in NO, H2O2, and MDA levels in kidney tissues after infection of lupus mice with live malaria. Similarly, the levels of NO and H2O2 were significantly decreased in the liver tissues of lupus mice after infection with live malaria. Conversely, GSH levels were obviously increased in both kidney and liver tissues after infection of lupus mice with either live or gamma-irradiated malaria. Liver and kidney functions were significantly altered after infection of lupus mice with live malaria. We further investigated the ultrastructural changes and detected the number of apoptotic cells in kidney and liver tissues in situ by electron microscopy and TUNEL assays. Our data reveal that infection of lupus mice with malaria confers protection against lupus nephritis.

Evaluation of Schistosoma haematobium 27-29 kDa antigen for immunodiagnosis of schistosomiasis haematobium.

The study demonstrated the immunodiagnostic potential of differrent Egyptian human Schistosoma haematobium antigens. ELISA was used to measure the levels of total immunoglobulin G (IgG) and IgG4 antibodies (Abs) against S. haematobium adult worm antigens (Ags) (SAWA), excretory/secretory Ags (E/S) and cysteine proteinase Ag (27-29 kDa) for diagnosis of schistosomiasis. SDS-PAGE profiles of S. haematobium Ags showed several bands for SAWA, E/S and 27-29 kDa Ags which are characteristic of infections with Schistosoma spp. Purified protein fraction showed a single homogenous band of 27-29 kDa. For summarizing the potency of S. haematobium Ags, sensitivety rate, negative predictive value and diagnostic efficacy were calculated between data of 40 human patients in ELISA. SAWA Ag recorded 85.0 %, 77%, 90.0% with total IgG & 90.0 %, 83% and 93.3% with IgG4 isotype, respectively. While, E/S recorded 87.5%, 80%, 92.0% with total IgG and 92.5%, 87%, 95.0% with IgG4 isotype, respectively. Purified 27-29 kDa Ag presents the higher significant (P<0.01) results recording 90.0%, 83%, 93.3% with total IgG and 97.5%, 95%, 98.3% with IgG4 isotype, respectively. The results proved that combining the detection of IgG4 isotype using the 27-29 kDa Ag in sera of schistosomiasis haematobium patients in ELISA test could represent an effective immunodiagnostic tool for detecting infection in low worm burden population. This test could be useful in sero-epidemiolocal studies in low endemic areas and in diagnosis of infection in travelers to schistosomiasis endemic areas.