Progress in the development and use of monoclonal antibodies to study the evolution and function of the immune systems in the extant lineages of ungulates.

Details on the origin and function of the immune system are beginning to emerge from genomic studies tracing the origin of B and T cells and the major histocompatibility complex. This is being accomplished through identification of DNA sequences of ancestral genes present in the genomes of lineages of vertebrates that have evolved from a common primordial ancestor. Information on the evolution of the composition and function of the immune system is being obtained through development of monoclonal antibodies (mAbs) specific for the MHC class I and II molecules and differentially expressed on leukocytes differentiation molecules (LDM). The mAbs have provided the tools needed to compare the similarities and differences in the phenotype and function of immune systems that have evolved during speciation. The majority of information currently available on evolution of the composition and function of the immune system is derived from study of the immune systems in humans and mice. As described in the present review, further information is beginning to emerge from comparative studies of the immune systems in the extant lineages of species present in the two orders of ungulates, Perissodactyla and Artiodactyla. Methods have been developed to facilitate comparative research across species on pathogens affecting animal and human health.

Pregnenolone protects the liver against doxorubicin-induced cellular injury by anti-inflammatory, antioxidant, and antiapoptotic mechanisms: role of Keap1/Nrf2/HO-1 and P-glycoprotein.

OBJECTIVE: Doxorubicin (DOX) is a widely used cytotoxic anthracycline antibiotic characterized by increased adverse effects that limit its clinical usefulness. Pregnenolone is a pregnane X receptor (PXR) agonist that increases the expression of xenobiotic transporters with anti-inflammatory and antioxidant potential. Thus, we hypothesized that pregnenolone would protect against DOX-induced hepatotoxicity. MATERIALS AND METHODS: Male Wistar rats (180-200 g) were randomized into four groups (n = 7): Control, Control + Pregnenolone (35 mg/kg/day, orally), DOX (15 mg/kg, i.p.) single dose on day five, and Pregnenolone + DOX. All treatments continued for seven consecutive days. Twenty-four hours after the last treatment, serum and liver tissues were collected for biochemical and histopathological assessment. The possible interaction between pregnenolone and DOX on cell viability was tested in HepG2 cells in vitro by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RESULTS: DOX treatment resulted in hepatic damage and fibrosis with increased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Liver samples of the DOX-treated group showed increased oxidative stress [malondialdehyde (MDA) and total nitrite/nitrate and decreased reduced glutathione (GSH) and superoxide dismutase (SOD)], increased hepatic tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), transforming growth factor-beta1 (TGF-ß1), and mRNA of interleukin-1beta (IL-1ß) and interleukin-6 (IL-6). Pretreating the rats with pregnenolone antagonized these DOX-induced effects. Moreover, pregnenolone upregulated the hepatic expression of Nrf2, heme oxygenase-1 (HO-1), and P-glycoprotein and decreased Keap1, opposing the effects of DOX. Moreover, pregnenolone prevented the DOX-induced activation and nuclear translocation of NFκB and increased cleaved caspase-3. Pregnenolone potentiated DOX-mediated cytotoxicity in HepG2 cells. CONCLUSIONS: These results illustrate the protective effects of pregnenolone against DOX-induced hepatotoxicity without limiting its anticancer activity.

Comparative analysis of the specificity of monoclonal antibodies developed against the bottlenose dolphin, Tursiops truncatus, TNF-α, IL1-ß, IL-6, IL-8, IL-10 with monoclonal antibodies made against ovine IFN-γ bovine IL-17A and IL-1ß revealed they recognize epitopes conserved on dolphin and bovine orthologues.

Opportunities to include Cetancodontamorpha in the study of the evolution of the immune system in the clades of Artiodactylamorpha, Ruminantiamorpha, Suinamorpha, and Camelidamorpha have increased with the use of the bottlenose dolphin, Tursiops truncatus, as a sentinel species to study the effects of environmental pollutants on the health of marine mammals. Efforts are currently underway to increase the number reagents needed for detailed studies. Thus far, screening of monoclonal antibodies (mAbs) made to leukocyte differentiation molecules (LDM) and the major histocompatibility (MHC) class I and class II molecules in Ruminantiamorpha have yielded some mAbs that recognize conserved epitopes expressed on orthologues in the bottlenose dolphin. More direct approaches are in progress to identify additional mAbs to bottlenose LDM and cytokines. As reported here, both direct and indirect approaches were used to identify mAbs specific for cytokines useful in monitoring the effects of environmental pollutants on the immune system. Immunization of mice with expressed bottlenose dolphin cytokines yielded mAbs specific for IFN-γ, TNF-α, IL-6, IL-8, IL-10, and IL-17A. Screening of previously developed mAbs used in livestock immunology research revealed mAbs developed against ovine IFN-γ and bovine IL-17 and IL-1ß recognize conserved epitopes in bottlenose dolphin orthologues. The mAbs identified in the present study expand the reagents available to study the function of the immune system in bottlenose dolphins and cattle.

Ex vivo Platforms to Study the Primary and Recall Immune Responses to Intracellular Mycobacterial Pathogens and Peptide-Based Vaccines.

Progress in the study of the immune response to pathogens and candidate vaccines has been impeded by limitations in the methods to study the functional activity of T-cell subsets proliferating in response to antigens processed and presented by antigen presenting cells (APC). As described in this review, during our studies of the bovine immune response to a candidate peptide-based vaccine and candidate rel deletion mutants in Mycobacterium avium paratuberculosis (Map) and Mycbacterium bovis (BCG), we developed methods to study the primary and recall CD4 and CD8 T-cell responses using an ex vivo platform. An assay was developed to study intracellular killing of bacteria mediated by CD8 T cells using quantitative PCR to distinguish live bacteria from dead bacteria in a mixed population of live and dead bacteria. Through use of these assays, we were able to demonstrate vaccination with live rel Map and BCG deletion mutants and a Map peptide-based vaccine elicit development of CD8 cytotoxic T cells with the ability to kill intracellular bacteria using the perforin-granzyme B pathway. We also demonstrated tri-directional signaling between CD4 and CD8 T cells and antigen-primed APC is essential for eliciting CD8 cytotoxic T cells. Herein, we describe development of the assays and review progress made through their use in the study of the immune response to mycobacterial pathogens and candidate vaccines. The methods obviate some of the major difficulties encountered in characterizing the cell-mediated immune response to pathogens and development of attenuated and peptide-based vaccines.

The emerging role of lncRNA MEG3 and MEG3 rs7158663 in hepatocellular carcinoma.

OBJECTIVE: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy in Egypt. Genetic and environmental factors play a role in its development. This study explored the association between the long non-coding RNA (lncRNA) MEG3 rs7158663 polymorphism, MEG3 expression, and the risk of HCC and other clinicopathologic characteristics in an Egyptian population. PATIENTS AND METHODS: This case-control study included 114 patients with HCC and 110 healthy controls. TaqMan Real-time PCR was used to analyze lncRNA MEG3 rs7158663. Serum MEG3 expression levels were measured using RT-PCR. RESULTS: The AA, GA+AA, and A alleles were associated with increased risk for HCC (adjusted odds ratio (OR) 11.84%, 95% CI 4.07-34.45, p < 0.0001; adjusted OR 3.18, 95% CI 1.79-5.67, p < 0.0001; and adjusted OR 2.87, 95% CI 1.91-4.34, p < 0.0001, respectively). The mutant genotype and allele were linked to an increased risk in male patients and patients ≥ 50 years old. MEG3 serum expression level was downregulated in HCC patients. The rs7158663 G > A polymorphism and downregulated MEG3 were significantly associated with larger tumor size and advanced disease stage. CONCLUSIONS: MEG3 rs7158663 single nucleotide polymorphisms and downregulated lncRNA MEG3 were associated with HCC risk and may represent diagnostic and bad prognostic factors for HCC patients.

Clinical and functional efficacy of gallium-arsenide super pulsed laser therapy on temporo mandibular joint pain with orofacial myalgia following healed unilateral cervicofacial burn - A randomized trial.

BACKGROUND: Cervicofacial burn (CB) is a unique type of burn, involving the lateral part of the face, neck and chest region with significant skin contractures. Temporomandibular joint (TJ) pain and orofacial myalgia (OM) are the major problems in physiotherapy context to treat. Laser is commonly used as an adjunct therapy in painful conditions. However, clinical studies are lacking in investigating the effects of gallium-arsenide (Ga-As) super pulsed laser therapy on temporomandibular joint pain and orofacial myalgia following healed cervicofacial burn patients. OBJECTIVE: To investigate the effects of clinical and functional efficacy of Ga-As super pulsed laser therapy on temporomandibular joint pain with orofacial myalgia following healed cervicofacial burn patients. METHODS: Through two block random sampling method, the eligible participants were randomized and allocated into active laser (Active-L; n = 18) and placebo laser (Placebo-L; n = 18) groups. The Active-L group received laser treatment and the Placebo-L group received placebo laser effect (inactive laser) with regular physiotherapy care for 3 times in a week for 4 weeks. Primary (pain intensity, pain threshold, pain frequency) and secondary (mouth opening, disability level and quality of life) measures were measured at baseline, after the end 4th week, 8th week and 6 month follow up. RESULTS: Baseline subjective and clinical attributes show homogenous presentation among the study groups (p > 0.05). After four weeks of treatment, and at the end of 6 months follow up, the pain intensity, 2.9 (CI 95% 2.80-3.00), pain threshold 19.2 (CI 95% -30.4 to -7.9), pain frequency 3.4 (CI 95% 3.14-3.65), mouth opening, -16.0 (CI 95%-16.5 to -15.4), disability level 11.3 (CI 95%11.14-11.45), and quality of life -31.7 (CI 95%-37.1 to -26.2) showed more improvement (p < 0.001) in Active-L group than Placebo-L group. CONCLUSION: The reports of this study proved that, four weeks active laser therapy with regular physiotherapy care has an ideal treatment protocol for temporomandibular joint pain with orofacial myalgia following healed cervicofacial burn. This study also provided a new knowledge for physiotherapists in the field of temporomandibular joint pain rehabilitation.

Advances in Understanding of the Immune Response to Mycobacterial Pathogens and Vaccines through Use of Cattle and Mycobacterium avium subsp. paratuberculosis as a Prototypic Mycobacterial Pathogen.

Lack of understanding of the immune response to mycobacterial pathogens has impeded progress in development of vaccines. Infection leads to development of an immune response that controls infection but is unable to eliminate the pathogen, resulting in a persistent infection. Although this puzzle remains to be solved, progress has been made using cattle as a model species to study the immune response to a prototypic mycobacterium, Mycobacterium a. paratuberculosis (Map). As chronicled in the review, incremental advances in characterizing the immune response to mycobacteria during the last 30 years with increases in information on the evolution of mycobacteria and relA, a gene regulating the stringent response, have brought us closer to an answer. We provide a brief overview of how mycobacterial pathogens were introduced into cattle during the transition of humankind to nomadic pastoralists who domesticated animals for food and farming. We summarize what is known about speciation of mycobacteria since the discovery of Mybacterium tuberculsis Mtb, M. bovis Mbv, and Map as zoonotic pathogens and discuss the challenges inherent in the development of vaccines to mycobacteria. We then describe how cattle were used to characterize the immune response to a prototypic mycobacterial pathogen and development of novel candidate vaccines.

A Low-Fat Diet Combined with Moderate-Intensity Aerobic Exercise is More Effective than a Low-Fat Diet or Aerobic Exercise Alone on Dyslipidemia and Depression Status in Obese Patients: A Randomized Controlled Trial.

BACKGROUND & OBJECTIVE: Exercise and dietary interventions are used to control dyslipidemia and depression in obese individuals, whilst rare investigations have examined the concurrent effects of a low-fat diet and moderate-intensity aerobic exercise training (MIAET) on dyslipidemia and depression in obese patients. Hence, we assessed the potential influences of a low-fat diet combined with MIAET on blood lipids and depression in those individuals. METHODS: Forty-two obese patients aged 30-50 years have been enrolled in this randomized controlled trial. They have been randomized equally into MIAET group (n=14, 60-70% of the maximum heart rate (Max HR), three sessions a week), a low-fat diet group (n=14, fat, 30% Kcal/day), and a low-fat diet plus MIAET (n=14) for 10 consecutive weeks. Body mass index (BMI), lipid profile, and Hamilton depression rating scale (HDRS) have been assessed on two occasions, pre and post- 10 weeks. RESULTS: It was demonstrated that a low-fat diet group showed an improvement in total cholesterol (T-Ch), p=0.046, with no changes in triglycerides (TGs), p=0.343, low-density lipoproteins (LDLs), p=0.187, and high-density lipoproteins (HDLs), p=0.224; however, MIAET group showed an improvement in TGs, p=0.042, HDLs, p=0.038 with no changes in T-Ch, p=0.126, and LDLs, p=0.368. Regarding the low-fat diet plus MIAET group, significant improvements were identified in TGs, p=0.003, T-Ch, p<0.001, LDLs, p=0.004, and HDLs, p<0.001. For the depression status, all groups showed a significant improvement in HDRS, p<0.001, with a low-fat diet plus MIAET group showing greater advantages, p<0.05. CONCLUSION: The results of the current trial suggest an important implication for promoting improvement in blood lipids and a reduction in depression status in obese patients with dyslipidemia following 10-week of a concurrent low-fat diet and moderate-intensity aerobic exercise more than low-fat diet or MIAET alone.

A Prospective Comparative Study of Pulsed High-Intensity Laser Therapy and Pulsed Electromagnetic Field on Chronic Nonspecific Low Back Pain.

Objective: This study explored the different effects of pulsed high-intensity laser therapy (HILT) versus pulsed electromagnetic field (EMF) in the treatment of chronic nonspecific low back pain (ChNsLBP). Methods: Between August and December 2019, 51 ChNsLBP participants with a mean age of 35.2 ± 8.6 years were enrolled in this prospective comparative study. At random, they were divided into three groups, 17 in each; HILT, EMF, and controls. HILT group was recruited for Nd:YAG laser using the following parameters: a wavelength of 1064 nm, fluency of 610-810 mJ, frequency of 10-40 Hz, average power of 10.5 W, and 120 µs short pulse duration in scanning mode. All groups received the treatment twice a week for 8 consecutive weeks. They were assessed for the modified Oswestry disability index (MODI), pain disability index (PDI), visual analog scale (VAS), and lumbar flexion range of motion (flex ROM) before and after 8 weeks of study program. Results: The results showed greater improvement in the HILT group (VAS, PDI, MODI, and lumbar flex ROM, p = 0.001) than the EMF group (VAS, p = 0.002, PDI, p = 0.045, MODI, p = 0.002, and lumbar flex ROM, p = 0.042), with significant difference between the two groups in favor of the HILT group (p ˂ 0.05). Conclusions: Depending on the results of the study, both HILT and EMF are useful physiotherapy modalities in the treatment of ChNsLBP with HILT exhibiting better outcomes than EMF. Clinical recommendations should be highlighted to instigate the use of HILT in the management of musculoskeletal disorders, distinctively ChNsLBP.

Seeing the siblings: Gender differences in emerging-adult siblings of individuals with autism spectrum disorder.

BACKGROUND: The present study focused on typically developing siblings (TDS) in emerging adulthood of individuals with autism spectrum disorder (ASD) and sought insight into how gender may interact with positive and negative affects in this population. In addition, we aimed to explore the gender differences as a moderator in the link between personal resources (i.e., family cohesion and flexibility coping strategy) and positive and negative affects among such TDS. An understanding of gender differences in this population should prove relevant to the development of potential interventions. METHOD: A total of 116 emerging adult (age 18-29) TDS of younger siblings with ASD (the latter were under the age of 18 at the time of data collection), 80 females and 36 males, participated in the study. All participants completed self-report measures. RESULTS: Female TDS reported higher negative affect than male TDS, while no differences emerged regarding positive affect. Female siblings reported higher family cohesion and higher flexibility in the forward-focused subscale of flexibility coping strategy, but not in its trauma-focused subscale, compared to male siblings. Additionally, gender moderates the links between family cohesion and positive affect but not negative affect. Gender also moderates the association between flexibility and negative affect, but not positive affect. CONCLUSIONS: This study highlights the gender differences among TDS in emerging adulthood of individuals with ASD in relation to negative affect, family cohesion, and flexibility coping strategy. Understanding the gender-specific internal and external experiences of TDS as interplaying with their resources, at the unique developmental stage of emerging adulthood, may afford to identify TDS in need and to suggest potential interventions.

Effect of Moderate-Intensity Aerobic Exercise on Hepatic Fat Content and Visceral Lipids in Hepatic Patients with Diabesity: A Single-Blinded Randomised Controlled Trial.

OBJECTIVE: Limited studies have assessed the effect of moderate-intensity continuous aerobic exercise on hepatic fat content and visceral lipids in hepatic patients with diabesity. This study was designed to evaluate hepatic fat content and visceral lipids following moderate-intensity continuous aerobic exercise in hepatic patients with diabesity. DESIGN: A single-blinded randomised controlled trial. METHODS: Thirty-one diabetic obese patients with nonalcoholic fatty liver disease were recruited into this study. The patients were randomly classified into exercise and control groups, fifteen patients in the exercise group and sixteen patients in the control group. The exercise group received an 8-week moderate-intensity continuous aerobic exercise program with standard medical treatment, while the control group received standard medical treatment without any exercise program. Hepatic fat content and visceral lipids were assessed before and after intervention at the end of the study. RESULTS: Baseline and clinical characteristics showed a nonsignificant difference between the two groups (p > 0.05). At the end of the intervention, the aerobic exercise showed significant improvements (serum triglycerides and low-density lipoproteins (LDLs), p ≤ 0.002, total cholesterol, p=0.004, visceral fats, p=0.016, glycated hemoglobin (HbA1C), p=0.022, high-density lipoproteins (HDLs), p=0.038, alanine transaminases (AL), p=0.044, intrahepatic triglyceride and HOMA-IR, p=0.046, and body mass index (BMI), p=0.047), while the control group showed a nonsignificant difference (p > 0.05). The postintervention analysis showed significant differences in favor of the aerobic exercise group (p < 0.05). CONCLUSIONS: Moderate-intensity continuous aerobic exercise reduces the hepatic fat content and visceral lipids in hepatic patients with diabesity. Recommendations should be prescribed for encouraging moderate-intensity aerobic exercise training, particularly hepatic patients with diabesity.

Effects of high-intensity interval and moderate-intensity continuous aerobic exercise on diabetic obese patients with nonalcoholic fatty liver disease: A comparative randomized controlled trial.

BACKGROUND: Some studies assessed the effect of aerobic exercise on diabetic obese patients with hepatic disease, while very limited studies compared high-intensity interval (HII) versus moderate-intensity continuous (MIC) on diabetic obese patients with non-alcoholic fatty liver disease (NAFLD). OBJECTIVES: This study was designed to assess the effects of HII versus MIC on intrahepatic triglycerides (IHTG) and visceral lipids in diabetic obese patients with NAFLD. DESIGN: Randomized controlled trial. METHODS: Forty-seven diabetic obese individuals with NAFLD were enrolled in this study. The individuals were randomly divided into 16 in HII group, 15 in MIC group, and 16 in the controls. HII group received HII exercise, MIC group received 8-week MIC exercise while the control group did not receive any exercise intervention. IHTG and visceral lipids were assessed pre- and post-intervention. RESULTS: Baseline and clinical characteristics showed nonsignificant difference among the 3 groups (P > .05). Both HII and MIC groups showed a significant reduction in hepatic fat and visceral lipids (P < .05), while the controls showed nonsignificant difference (P > .05) after completing the study intervention. Postintervention analysis showed nonsignificant changes between the HII and MIC groups (P > .05). CONCLUSIONS: Exercise training wither HII or MIC aerobic exercise reduces IHGT and visceral lipids in diabetic obese patients with NAFLD. No differences were observed between the effects of both exercise programs on diabetic obese patients with NAFLD.

relA is Achilles' heel for mycobacterial pathogens as demonstrated with deletion mutants in Mycobacterium avium subsp. paratuberculosis and mycobacterium bovis bacillus Calmette-Guérin (BCG).

Studies with Mycobacterium avium subsp. paratuberculosis (Map) in cattle revealed deletion of relA, a global regulator gene, abrogated ability of the mutant to establish a persistent infection, attributed to development of an immune response that cleared infection. Analysis of the recall response demonstrated presence of CD8 cytotoxic T cells that kill intracellular bacteria. Replication of the primary response demonstrated the CTL response could be elicited with the ΔMap/relA mutant or the target of the immune response, a 35 kD membrane protein. Follow up comparative studies with Mycobacterium bovis bacillus Calmette-Guérin (BCG) and a BCG relA (ΔBCG/relA) deletion mutant revealed deletion of relA enhanced the CTL response compared to BCG. Analysis of the cytokine profile of cells proliferating in response to stimulation with BCG or BCG/relA showed increased expression of IFN-γ, TNF-α, and IL-17 by cells stimulated with ΔBCG/relA in comparison with BCG. The proliferative and CTL responses were markedly reduced in response to stimulation with heat killed BCG or ΔBCG/relA. Intracellular bacterial killing was mediated through the perforin, granzyme B (GnzB), and the granulysin pathway. The data indicate relA is the Achilles' heel for pathogenic mycobacteria and deletion may be key to improving efficacy of attenuated vaccines for mycobacterial pathogens.

Simultaneous cognate epitope recognition by bovine CD4 and CD8 T cells is essential for primary expansion of antigen-specific cytotoxic T-cells following ex vivo stimulation with a candidate Mycobacterium avium subsp. paratuberculosis peptide vaccine.

Studies in cattle show CD8 cytotoxic T cells (CTL), with the ability to kill intracellular bacteria, develop following stimulation of monocyte-depleted peripheral blood mononuclear cells (mdPBMC) with antigen presenting cells (APC, i.e. conventional dendritic cells [cDC] and monocyte-derived DC [MoDC]) pulsed with MMP, a membrane protein from Mycobacterium avium subsp. paratuberculosis (Map) encoded by MAP2121c. CTL activity was diminished if CD4 T cells were depleted from mdPBMC before antigen (Ag) presentation by APC, suggesting simultaneous cognate recognition of MMP epitopes presented by MHC I and MHC II molecules to CD4 and CD8 T cells is essential for development of CTL activity. To explore this possibility, studies were conducted with mdPBMC cultures in the presence of monoclonal antibodies (mAbs) specific for MHC class I and MHC class II molecules. The CTL response of mdPBMC to MMP-pulsed APC was completely blocked in the presence of mAbs to both MHC I and II molecules and also blocked in the presence of mAbs to either MHC I or MHC II alone. The results demonstrate simultaneous cognate recognition of Ag by CD4 and CD8 T cells is essential for delivery of CD4 T cell help to CD8 T cells to elicit development of CTL.

Novel TiO2/GO/CuFe2O4 nanocomposite: a magnetic, reusable and visible-light-driven photocatalyst for efficient photocatalytic removal of chlorinated pesticides from wastewater.

A TiO2/GO/CuFe2O4 heterostructure photocatalyst is fabricated by a simple and low-cost ball-milling pathway for enhancing the photocatalytic degradation of chlorinated pesticides under UV light irradiation. Based on the advantages of graphene oxide, TiO2, and CuFe2O4, the nanocomposite exhibited visible light absorption, magnetic properties, and adsorption capacity. Integrated analyses using XRD, SEM, TEM, and UV-visible techniques demonstrated that the nanocomposite exhibited a well-defined crystalline phase, sizes of 10-15 nm, and evincing a visible light absorption feature with an optical bandgap energy of 2.4 eV. The photocatalytic degradations of 17 different chlorinated pesticides (persistent organic pollutants) were assayed using the prepared photocatalyst. The photocatalytic activity of the nanocomposite generated almost 96.5% photocatalytic removal efficiency of typical pesticide DDE from water under UV irradiation. The superior photocatalytic performance was exhibited by the TiO2/GO/CuFeO4 catalyst owing to its high adsorption performance and separation efficiency of photo-generated carriers. The photocatalyst was examined in 5 cycles for treating uncolored pesticides with purposeful separation using an external magnetic field.

Purine versus non-purine xanthine oxidase inhibitors against cyclophosphamide-induced cardiac and bone marrow toxicity in rats.

BACKGROUND AND AIM: Cancer is a fatal and serious disease. Cyclophosphamide (CYC) is a commonly used anticancer drug. Cardiotoxicity and myelotoxicity are life-threatening side effects of CYC treatment. We aimed to evaluate the effect of the xanthine oxidase (XO) inhibitors, allopurinol (ALL) and febuxostat (FEB), on CYC-induced cardio- and hematopoietic toxicity in rats. METHODS: ALL (100 mg/kg/day) or FEB (10 mg/kg/day) were administered orally to rats in the presence and absence of CYC (200 mg/kg kg i.p. single dose) treatment. Serum creatine kinase-MB creatine kinase myocardial band (CK-MB) and lactate dehydrogenase (LDH) activities were estimated. Complete blood counting (CBC), cardiac and bone marrow XO activity, malondialdehyde level, and superoxide dismutase activity were determined. Cardiac and bone marrow histopathological changes were also evaluated. RESULTS: ALL and FEB significantly decreased CK-MB and LDH induced by CYC. Disturbed levels of XO, oxidative stress parameters, and CBC were also corrected by both XO inhibitors tested, with amelioration of cardiac histopathological changes caused by CYC. Treatment with FEB, but not ALL, prior to CYC challenges normalized bone marrow histopathological changes. CONCLUSION: These results suggest that both XO inhibitors tested; ALL and FEB can ameliorate CYC-induced cardiotoxicity. However, only FEB can protect against CYC-induced myelotoxicity, whereas ALL, to the contrary, might aggravate it.

Clinical value of soluble urokinase type plasminogen activator receptors in chronic kidney disease.

Chronic kidney disease (CKD) will progress to end stage without treatment, the decline off renal function may not linear. A sensitive marker such as soluble urokinase-type plasminogen activator receptors (suPARs) may allow potential intervention and treatment in earlier stages of CKD. OBJECTIVES: This study was designed to measure plasma (suPAR) in patients with CKD with different stages and to find its correlation with the disease severity. METHODS: This study was conducted on 114 subjects, 84 were patients with different stages and different causes of CKD, and 30 healthy subjects as controls. Blood urea, serum creatinine, serum high-sensitive C-reactive protein, estimated glomerular filtration rate, and 24 hours proteinuria were measured, renal biopsy was done for all patients, and plasma (suPAR) was measured using enzyme-linked immunosorbent assay. RESULTS: suPAR plasma levels were significantly higher in patients with CKD (7.9 ±â€Š3.82 ng/mL) than controls (1.76 ±â€Š0.77 ng/mL, P < .001). suPAR correlated with the disease severity. In stage 1 to 2 group, it was 3.7 ±â€Š1.5 ng/mL, in stage 3 to 4, it was 10.10 ±â€Š1.22 ng/mL, and in stage 5 group, it was 12.34 ±â€Š0.88 ng/mL; the difference between the 3 groups was highly significant (P < .001). A cutoff point 2.5 ng/mL of suPAR was found between controls and stage 1 group. According to the cause of CKD, although patients with obstructive cause and those with focal glomerulosclerosis had the higher levels 9.11 ±â€Š3.32 ng/mL and 8.73 ±â€Š3.19 ng/mL, respectively, but there was no significant difference between patients with CKD according to the cause of the CKD. CONCLUSION: Plasma (suPAR) increased in patients with CKD and correlated with disease severity.

Similar effects of low to moderate-intensity exercise program vs moderate-intensity continuous exercise program on depressive disorder in heart failure patients: A 12-week randomized controlled trial.

BACKGROUND: Heart failure related depression is recently increased worldwide. Heart failure (HF) disease is identified as a critical cause of increasing morbidity, hospital readmission, and mortality. The most important purpose of treatment of HF disease is to relief disease problems, improve functional performance, and achieve better quality of life. OBJECTIVES: This study was proposed to evaluate the effects of low to moderate-intensity exercise program vs moderate-intensity continuous exercise program on the level of depressive disorder in heart failure patients. STUDY DESIGN: 12-week randomized controlled trial. METHODS: Sixty nine HF patients with mild to moderate level of depression and ejection fraction <40% were examined before and after 12-week intervention. Their age was ranged from 40 to 60 years. Patients were randomly classified into 3 groups. Group I (n = 23) received low to moderate intensity exercise program (LMIEP), group II (n = 23) received moderate-intensity exercise program (MICEP), and group III (n = 23) did not receive any exercise program (Non-exercised group). All patients were instructed to conduct home-based exercise with their pharmacological therapy. The level of depression was evaluated before and after 12 weeks of the intervention program. RESULTS: The 3 study groups were associated with significant decrease of depression level (P < .05). Significant differences were exhibited between the 3 groups in favor to both exercise programs (P < .05) with non-significant differences between the 2 exercise programs (P > .05). CONCLUSIONS: Both exercise programs had positive effects in reducing the severity of depression in HF patients. Low to moderate and moderate-intensity exercise programs should be proposed for depression illness specially patients with heart failure.

Pattern of CD14, CD16, CD163 and CD172a expression on water buffalo (Bubalus bubalis) leukocytes.

Previous studies on the immune system of water buffalo (Bubalus bubalis) using cross-reactive monoclonal antibodies (mAbs) revealed significant similarities and differences to the bovine immune system. Herein, we extend these studies and document the pattern of expression of CD14, CD16, CD163 and CD172a on buffalo leukocytes using a set of cross-reactive mAbs that are known to recognize conserved epitopes within orthologous molecules in cattle, sheep and goats. Buffalo leukocytes were isolated and subjected to mAb labelling for flow cytometry. Single color flow cytometry confirmed mAbs recognition of buffalo orthologues of CD14, CD16, CD163 and CD172a, and revealed consistent patterns of expression similar to that reported in other ruminants. Multicolor flow cytometry revealed that buffalo CD14+ monocytes uniquely co-express CD16, CD163 and CD172a, whereas buffalo granulocytes co-express CD16 and CD172a. This study expands mAbs available to define and study the buffalo monocytes, and also extends information available on the unique features of the buffalo immune system.

A peptide-based vaccine for Mycobacterium avium subspecies paratuberculosis.

Recent efforts to develop a live attenuated vaccine against Mycobacterium avium subsp. paratuberculosis (Map), the causative agent of Johne's disease (JD), revealed relA is important in Map virulence. Deletion of the relA gene impairs the ability of Map to establish a persistent infection. Analysis of the basis for this observation revealed infection with a relA deletion mutant (ΔrelA) elicits development of cytotoxic CD8 T cells (CTL) with the ability to kill intracellular bacteria. Further analysis of the recall response elicited by ΔrelA vaccination showed a 35 kDa membrane peptide (MMP) is one of the targets of the immune response, suggesting it might be possible to develop a peptide-based vaccine based on MMP. To explore this possibility, ex vivo vaccination studies were conducted with MMP alone and incorporated into a nanoparticle (NP) vector comprised of poly (D, L-lactide-co-glycolide) and monophosphoryl lipid A (PLGA/MPLA). As reported, ex vivo vaccination studies showed CD8 CTL were elicited with classic and monocyte derived dendritic cells (cDC and MoDC) pulsed with MMP alone and incorporated into a PGLA/MPLA vector. Incorporation of MMP into a NP vector enhanced the ability of CD8 CTL to kill intracellular bacteria. The findings indicate incorporation of MMP into a PGLA/MPLA nanoparticle vector is one of the possible ways to develop a MMP based vaccine for Johne's disease.