Bee venom acupuncture therapy ameliorates neuroinflammatory alterations in a pilocarpine-induced epilepticus model

Metabolic Brain Disease - Bee venom (BV) is applied in different traditional medicinal therapies and is used worldwide to prevent and treat many acute and chronic diseases. Epilepsy has various...     

Ellagic acid reduces murine schistosomiasis mansoni immunopathology via up-regulation of IL-10 and down-modulation of pro-inflammatory cytokines production

Context: The main immunopathology in schistosomiasis mansoni consists of a granulomatous inflammatory and fibrosing reaction in the liver and intestine against tissue trapped parasite eggs, which is mediated by CD4^+?T cells. Ellagic acid (EA), a natural phenolic compound found in fruits and nuts, has potent anti-oxidant and anti-inflammatory properties.

Objective: The aim of the present study was to evaluate the potential effect of EA in the treatment of murine schistosomiasis mansoni and its induced immunopathology.

Materials and methods: Mice were infected, each with 40 Schistosoma mansoni (S. mansoni) cercariae and treated with EA at a total dose of 600?mg/kg body weight. At week eight of infection, mice were sacrificed; worm and egg burden were estimated; hepatic granuloma volume and collagen fibers deposition were evaluated; splenocytes were prepared and cultured in the presence of S. mansoni antigens.

Results: EA treatment did not show any significant effect on worm or egg burden. However, hepatic granuloma volume and collagen fibers deposition were largely reduced with EA treatment. EA treatment augmented specific IL-10 production in response to S. mansoni antigenic stimulation. However, specific IL-1β, IL-4, IL-12, IL-13, IL-17A, TNF-α and IFN-γ production were significantly reduced with ex vivo and in vivo EA treatment. Serum IgM and IgG levels significantly increased, whereas specific IgA and IgE levels did not significantly change with EA treatment.

Conclusion: EA treatment modulates cellular and humoral immune responses of infected mice and leads to a significant reduction of liver pathology in acute murine schistosomiasis mansoni.     

Association between cytokine genes polymorphisms and type 1 diabetes: a case-control study on Saudi population

Background: Association studies of genes encoding cytokines that play an important role in inflammatory response represent one approach to finding type 1 diabetes (T1D) disease genes. The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) within cytokine genes with T1D in a cohort of Saudi subjects. Methods: A total of 300 well-characterized type 1 diabetic patients and 300 T1D-free control subjects were enrolled in this investigation. Cytokine SNPs were genotyped by using Polymerase chain reaction (PCR) with sequence-specific primers. Results: Our data revealed that IFN-γ +874T allele carriers [odds ratio (OR) = 1.87, p < 0.001] and TT homozygotes (OR = 1.28, p < 0.001) were significantly more susceptible to developing T1D than the A allele carriers. In addition, TNF-α ?308A allele carriers (OR = 1.73, p < 0.001) and AA homozygotes (OR = 1.74, p < 0.001) were also overrepresented among the diabetics than G allele carriers. IL-4 ?590C/T TT homozygotes (OR = 2.23, p < 0.001) were significantly more susceptible to develop T1D than CC genotypes, whereas CT heterozygotes were not significantly associated (OR = 1.43, p = 0.78) with T1D. Furthermore, IL-4 T allele was statistically associated with T1D patients compared to control group (OR = 2.24, p < 0.001). Similarly, IL-1β ?511C/T TT homozygotes (OR = 1.85, p = 0.012) and the T allele (OR = 1.85, p < 0.001) were significantly more susceptible to T1D than CC genotypes, whereas TC heterozygotes (OR = 1.04, p = 0.86) were not significantly associated with T1D. Conclusion: Our data concluded that IFN-γ +874T allele, TNF-α ?308A allele, IL-1β ?511T allele, and IL-4 ?590T allele could be considered risk factors for T1D development in Saudi subjects.     

In vivo schistosomicidal activity of three novels 8-hydroxyquinoline derivatives against adult and immature worms of Schistosoma mansoni

Schistosomiasis control is widely dependent on a single drug, praziquantel (PZQ). The potential for development of resistance to PZQ has justified the search for new alternative chemotherapies. In a previous study, we have been reported that three of 8-hydroxyquinoline derivatives namely: 3-((8-hydroxyquinolin-5-yl) sulfonyl) pentane-2,4-dione (HQSP), 5-((2,4-diphenyl-3H-benzo[b][1,4]diazepin-3-yl) sulfonyl) quinolin-8-ol (HQBD), and 5-((2,4-diphenyl-3H-pyrido[3,4-b][1,4] diazepin-3-yl) sulfonyl) quinolin-8-ol (HQPD) possess a potent anti-schistosomal activity in vitro. The aim of the present study was to evaluate the in vivo schistosomicidal effect of these three compounds on adult and immature worms of Schistosoma mansoni and their induced pathology. Treatment of S. mansoni-infected mice with 1000, 250, 150, and 200 mg/kg body weight of PZQ, HQSP, HQBD, and HQPD, respectively, reduced adult and immature worm burden by 94.63 and 31.32 %, 73.63 and 5.45 %, 76.5 and 28.11 %, and 81.25 and 56.84 %, respectively, compared to infected untreated mice. Moreover, numbers of egg per gram liver and intestine were decreased by 84 and 95.51 %, 47.84 and 46.28 %, 53.18 and 59.37 %, and 54.22 and 67.26 as a result of PZQ, HQSP, HQBD, and HQPD treatment, respectively. Hepatic granuloma volume was also reduced by 40.10, 42.96, 35.72, and 72.09 % due to PZQ, HQSP, HQBD, and HQPD treatment, respectively. In addition, hepatic histopathological alterations and collagen fiber deposition that accompanied with S. mansoni infection were largely retrieved with different treatments, especially HQPD treatment. Furthermore, humoral immune response, especially IgG response against S. mansoni antigens, was augmented with different treatments. This study concluded that among the three tested 8-hydroxyquinoline derivatives, HQPD is the most effective compound against adult and pre-mature worms of S. mansoni and can be used for the development of a new schistosomicidal drug.