Relationship between Cytokines and Metabolic Syndrome Components: Role of Pancreatic-Derived Factor, Interleukin-37, and Tumor Necrosis Factor-α in Metabolic Syndrome Patients.

The metabolic syndrome (MetS) is a serious public health issue that affects people all over the world. Notably, insulin resistance, prothrombotic activity, and inflammatory state are associated with MetS. This study aims to explore the relationship between cytokines and tumor necrosis factor-α (TNF-α), pancreatic-derived factor (PANDER), and interleukin (IL-)-37 and the accumulation of MetS components. Eligible participants were divided into four groups as follows: group 1, patients with dyslipidemia; group 2, patients with dyslipidemia and obesity; group 3, patients with dyslipidemia, obesity, and hypertension; and group 4, patients with dyslipidemia, obesity, hypertension, and hyperglycemia. This study exhibited that serum levels of TNF-α and PANDER were significantly elevated (P < 0.001) in the MetS groups, while IL-37 level and IL-37 mRNA expression were significantly decreased (P < 0.001) relative to healthy controls. Moreover, this study has revealed significant correlations (P < 0.001) between MetS components and TNF-α, PANDER, and IL-37 levels in MetS patients. The aforementioned results suggested the association between the proinflammatory cytokine (TNF-α and PANDER) and anti-inflammatory cytokine (IL-37) with the accumulation of MetS components. Hence, the overall outcome indicated that PANDER and IL-37 may be considered novel biomarkers associated with increased risk of MetS and can be used as a promising therapeutic target in preventing, ameliorating, and treating metabolic disorders. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01079-z.

Anti-inflammatory, antioxidant, anti-fibrotic and schistosomicidal properties of plumbagin in murine schistosomiasis.

Schistosomiasis is still a major health problem affecting nearly 250 million people worldwide and causes approximately 280,000 deaths per year. The disease causes a serious granulomatous inflammatory response that produces significant mortality. Plumbagin reportedly displays anti-inflammatory, anti-fibrotic, antioxidant and anthelmintic properties. This study further elucidates these properties. Mice were infected with schistosomes and divided into five groups: non-infected untreated (C); infected untreated (IU); non-infected treated with plumbagin (P); infected treated with plumbagin (PI) and infected treated with praziquantel (PZ). Mice treated with 20 mg plumbagin/kg body weight showed reduction of 64.28% and 59.88% in male and female animals, respectively. Also, the number of eggs/g tissue was reduced 69.39%, 68.79% and 69.11% in liver, intestine and liver/intestine combined, respectively. Plumbagin alleviated schistosome-induced hepatosplenomegaly and reduced hepatic granuloma and liver collagen content by 62.5% and 35.26%, respectively while PZQ reduced hepatic granuloma and liver collagen content by 41.11% and 11.21%, respectively. Further, plumbagin treatment significantly (p < .001) reduced IL-4, IL-13, IL-17, IL-37, IFN-γ, TGF-ß and TNF-α levels and significantly (p < .001) upregulated IL-10. Plumbagin treatment restored hepatic enzymes activity to nearly normal levels and induced an increase in catalase, SOD, GSH, total thiol and GST in liver tissue homogenate. NO and LPO content was, however, decreased. Moreover, serum IgG levels significantly increased. The present study is the first to report immunomodulatory and schistosomicidal activities of plumbagin in schistosomiasis.

Possible association of rotavirus IgG with cytokine expression levels and dyslipidemia in rotavirus-infected type 1 diabetic children.

BACKGROUND: Rotavirus (RV) has been postulated as a viral trigger for the onset of autoimmune disorders, such as type 1 diabetes (T1D). This study aimed to examine the conceivable association of RV IgG with cytokine levels and dyslipidemia in the pathogenesis of pediatric T1D. METHODS: This study included 30 healthy controls and 80 children with T1D who were divided into two groups based on the time since their T1D diagnosis: newly diagnosed (ND ≤ 1 year; n = 30) and previously diagnosed (PD > 1 year; n = 50). ND and PD patients were also separated into negative and positive according to IgG detection (RV IgG-, ND-, and PD-; RV IgG+, ND+, and PD+). RESULTS: Positive polymerase chain reaction for RVs was evidenced in 7.5% of children with T1D. Anti-RV IgG was 30% and 36% in ND and PD, respectively, compared to healthy controls (2 of 30, 6.6%; P < 0.05). Fasting blood sugar and hemoglobin A1c significantly increased in PD+ compared to PD-. Interferon-γ and interleukin (IL)-15 levels significantly increased. IL-12 and IL-22 mRNA expression was upregulated in ND+ patients compared to that in ND- patients. IL-37 mRNA expression was significantly downregulated in ND- and ND+ patients compared to that in healthy controls. Total cholesterol and high- and low-density lipoprotein-cholesterol levels were significantly lower in PD+ than in PD-; whereas triglyceride levels were higher than those in healthy controls. CONCLUSIONS: This study suggested that anti-RV IgG may have a role in the pathogenesis, development, and progression of T1D, and RV infections are implicated in dyslipidemia and inflammation status.

Role of free style Libre-Flash Glucose Monitoring: Glycemic control of Type-1 Diabetes.

BACKGROUND & OBJECTIVE: Type-1 diabetics (T1D) usually do not meet guidelines for glycaemic control. This study aimed to determine the benefit of free style libre-flash glucose monitoring system (FSL-FGM) in lowering glycated hemoglobin (HbA1c) in poorly controlled T1D patients. METHODS: This prospective two single arm clinical study included 273 T1D patients, and data collected at one, six and 18 months with concomitant extraction of samples for HbA1c basal and at six and 18 months. The study was conducted in Prince Mansour Military Hospital at Taif, Saudi Arabia from June 2017 to November 2018. RESULTS: HbA1c % was significantly diminished in patients used FSL-FGM at 6 and 18 months. The median percentage difference in HbA1c at 6 and 18 months versus basal was significantly decreased in those using FSL-FGM. Within diabetics using FSL-FGM, the median difference in HbA1c after 18 months was significantly decreased in patients with HbA1c >10% compared to those with HbA1c <10%. Estimated HbA1c by FSL showed a significant correlation with HbA1C assayed in the blood. The snapshot information showed a highly significant difference in average glucose with low significant difference in hypoglycemia parameters. The FSL-FGM provides significant changes in HbA1c in diabetic patients without observed risk for hypoglycemia. CONCLUSIONS: The dynamic way of blood glucose monitoring using FSL-FGM provides improvement in HbA1c in diabetic patients without observed risk for hypoglycemia.

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-1ß -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-1ß -511T allele, and IL-4 -590T allele could be considered risk factors for T1D development in Saudi subjects.

The Potential Role of PTPN-22 C1858T Gene Polymorphism in the Pathogenesis of Type 1 Diabetes in Saudi Population.

BACKGROUND: Recent investigations have reported an association between protein tyrosine phosphatase non-receptor type-22 (PTPN-22) gene polymorphism and susceptibility to the development of type 1 diabetes (T1D) in some populations and not in others. In this study, we aimed to investigate the association of PTPN-22 C1858T polymorphism with T1D in Saudi children. METHODS: A cohort of 372 type 1 diabetic children and 372 diabetes-free subjects was enrolled in the current investigation. The PTPN-22 C1858T polymorphism was identified using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Our data showed that the frequency of CT and TT genotypes of PTPN-22 C1858T was higher in T1D children (17.7% and 4.3%, respectively) compared to healthy controls (4.8% and 1.6%, respectively), and both genotypes were statistically associated with T1D patients (OR = 4.4, 95% CI: 2.55-7.58, p < 0.001; and OR = 3.2, 95% CI: 1.23-8.28, p = 0.017, respectively). Moreover, the 1858T allele was significantly associated with T1D patients compared to the C allele (OR = 3.2, 95% CI: 1.59-6.88, p < 0.001). In addition, the T allele was significantly associated with elevated levels of HbA1c, anti-GAD, and anti-insulin antibodies (p < 0.001) and a lower concentration of C-peptide (p < 0.001) in T1D children. CONCLUSION: The data presented here suggests that the T allele of PTPN-22 C1858T polymorphism might be a risk factor for T1D development in Saudi children.

Association of IL-37 gene polymorphisms with susceptibility to tuberculosis in Saudi subjects.

Tuberculosis (TB) is one of the most common infectious diseases worldwide. IL-37, a novel member of the IL-1 family, has anti-inflammatory activity. Various cytokine genes polymorphisms are reportedly associated with susceptibility to TB infection. However, an association between genetic variations in the IL-37 gene and susceptibility to TB infection has not been investigated. The aim of this case-control study was therefore to identify such an association in Saudi subjects, in which five single-nucleotide polymorphisms (SNPs) in the IL-37 gene were assessed. Serum concentrations of IL-37 were evaluated using ELISA, and genetic variants genotyped by multiplex PCR and ligase detection reaction. It was found that the C/C genotype of rs2723176 (-6962 A/C) occurs significantly more frequently in patients with active TB and that the C allele of this SNP is associated with TB. In addition, the C allele of rs2723176 SNP was associated with high circulating concentrations of IL-37. However, the genotype and allele frequency of the other four SNPs (rs3811046, rs3811047, rs2723186 and rs2723187) were not significantly associated with TB infection. In conclusion, the present data suggest that rs2723176 SNP of IL-37 is involved in the development of TB infection. Furthermore, high circulating concentrations of IL-37 may have a negative effect on protective immunity against TB infection.

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-1ß, 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.

Ellagic acid alleviates adjuvant induced arthritis by modulation of pro- and anti-inflammatory cytokines.

Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown aetiology, but it is now clear that pro-inflammatory cytokines play a central role in its pathogenesis. Ellagic acid (EA) has a variety of biological activities including anti-oxidant, anti-inflammatory, and anti-cancer properties. The aim of the present study was to evaluate the potential effect of ellagic acid on the prevention and/or treatment of adjuvant induced arthritis (AIA) model in mice. Ellagic acid treatment was started one week before AIA induction and continued for three weeks after induction of AIA. Ellagic acid treatment significantly (p < 0.01) inhibited foot paw oedematous swelling and attenuated AIA-associated pathology. Ellagic acid significantly (p < 0.01) reduced serum levels of pro-inflammatory cytokines: interleukin 1ß (IL-1ß), tumor necrosis factor α (TNF-α), and interleukin 17 (IL-17). However, serum levels of IL-10 and interferon γ (IFN-γ) significantly increased (p < 0.01 and p < 0.05, respectively), while serum level of transforming growth factor ß (TGF-ß) did not significantly alter with EA treatment. In conclusion, these results suggest that EA attenuated AIA-associated pathology in the mouse model by downregulation of pro-inflammatory cytokines and upregulation of anti-inflammatory cytokines.

Neonatal infections in Saudi Arabia: Association with cytokine gene polymorphisms.

In recent years, many studies have reported potential associations between cytokine gene polymorphisms and the development, course, and outcome of sepsis, often with apparently conflicting results. The objective of this study was to investigate single nucleotide polymorphism (SNP) in the interleukin (IL)-1ß -31 T/C, IL-6 -174 G/C, tumor necrosis factor α (TNF-α) -308 G/A, and interferon γ (IFN-γ) +874 A/T genes for their possible association with susceptibility to early onset sepsis (EOS) in Saudi newborn infants. A total of 205 newborn infants aged 1-2 days were consecutively enrolled onto the study having met the inclusion criteria (as per the research protocol). DNA was extracted from filter papers using the Chelex-100 method. The cytokines SNP were genotyping using Taqman 5' nuclease allelic discrimination. For cytokine measurements we used the commercially available Enzyme-Linked Immunosorbent Assay (ELISA) kit. Our results show that the circulating IL-1ß, IL-6, TNF-α, and IFN-γ were significantly (p < 0.001) elevated in EOS patients compared to suspected and sepsis-free control groups; and IL-1ß -31C, IL-6 -174G, TNF-α -308G, and IFN-γ +874A alleles were associated with EOS in Saudi infants. In conclusion, analysis of cytokines concentrations and SNP for the four tested genes can be used as a predictor of sepsis outcome in newborns.

IFN-gamma and TNF associated with severe falciparum malaria infection in Saudi pregnant women.

BACKGROUND: Tumour necrosis factor (TNF) and interferon gamma (IFN-γ), encoded by TNF-836 C/A (rs 1800630) and IFN-γ -1616 C/T (rs2069705) genes, are key immunological mediators that are believed to both play protective and pathological roles in malaria. The aim of this study was to investigate the relationship between TNF-836 C/A and IFN-γ-1616 C/T polymorphism and susceptibility to severe malaria in pregnant women. METHODS: A prospective cohort (cross-sectional) study was conducted in pregnant women attending the out-patient clinic in King Fahad Specialist Hospital in Jazan (KFSHJ), with a clinical diagnosis of malaria. A total of one hundred and eighty six pregnant women were genotyped for single nucleotide polymorphism (SNP) for TNF and IFN-γ using Taqman® MGB Probes. Serum cytokine concentrations were measured by sandwich ELISA method. RESULTS: A hospital case-control study of severe malaria in a Saudi population identified strong associations with individual single-nucleotide polymorphisms in the TNF and IFN-γ genes, and defined TNF-836 C and IFN-γ-1616 T genotypes and alleles which were statistically significantly associated with severe malaria infection. Furthermore, TNF-836 CC and IFN-γ-1616 TT genotypes were associated with higher serum concentration of TNF and IFN-γ, respectively, and with susceptibility to severe malaria. CONCLUSIONS: This data provides a starting point for functional and genetic analysis of the TNF and IFN-γ genomic region in malaria infection affecting Saudi populations.

Hesperidin inhibits inflammatory response induced by Aeromonas hydrophila infection and alters CD4+/CD8+ T cell ratio.

BACKGROUND: Aeromonas hydrophila is an opportunistic bacterial pathogen that is associated with a number of human diseases. Hesperidin (HES) has been reported to exert antioxidant and anti-inflammatory activities. OBJECTIVES: The aim of this study was to investigate the potential effect of HES treatment on inflammatory response induced by A. hydrophila infection in murine. METHODS: A. hydrophila-infected mice were treated with HES at 250 mg/kg b.wt./week for 4 consecutive weeks. Phagocytosis, reactive oxygen species production, CD4(+)/CD8(+) T cell ratio, and CD14 expression on intestinal infiltrating monocytes were evaluated. The expression of E-selectin and intercellular adhesion molecule 1 on stimulated HUVECs and RAW macrophage was evaluated. RESULTS: Percentage of CD4(+) T cells in the intestinal tissues of infected treated mice was highly significantly increased; however, phagocytic index, ROS production, CD8(+) T cells percentage, and CD14 expression on monocytes were significantly reduced. On the other hand, HES significantly inhibited A-LPS- and A-ECP-induced E-selectin and ICAM-1 expression on HUVECs and ICAM-1 expression on RAW macrophage. CONCLUSION: Present data indicated that HES has a potential role in the suppression of inflammatory response induced by A. hydrophila toxins through downmodulation of ROS production and CD14 and adhesion molecules expression, as well as increase of CD4(+)/CD8(+) cell ratio.

Neonatal infections in Saudi Arabia: association with C-reactive protein, CRP -286 (C>T>A) gene polymorphism and IgG antibodies.

BACKGROUND: C-reactive protein (CRP) is a nonspecific, acute-phase protein that rises in response to infectious and non-infectious inflammatory processes. Infections are the single largest cause of neonatal deaths globally.The primary aim of this study is to examine the association between CRP gene polymorphism and serum levels of CRP in correlation with early onset sepsis (EOS) infection in newborns living in Taif city, Saudi Arabia. The second aim is to examine the relationship between specific IgG/IgG subclasses and early onset sepsis (EOS) infection among these newborns. METHODS: Staphylococcus aureus (S. aureus) is one of the most common organisms related to sepsis infection in the newborn at King Abdel Aziz Specialist Hospital (KAASH). This study was conducted in Taif city, at KAASH's neonatal intensive care unit between March and August 2012. Neonates were consecutively enrolled onto the study having met our inclusion criteria (as per our research protocol).The CRP concentration level was analysed using NycoCard CRP Single Test. CRP -286 (C>T>A) A polymorphisms were analyzed using Pyrosequencing technology for CRP genotyping. IgG subclasses were analysed in the study population using ELISA. RESULT: Logistic regression analyses showed that the AA and AC genotypes were negatively associated amongst EOS neonates compared to suspected neonates. The frequency of CC and CT were significantly associated with the EOS neonates compared to the suspected group. The levels of specific IgG1, IgG2 and IgG3 antibodies were significantly lower amongst EOS compared to the suspected group. CONCLUSIONS: Taken together, the CRP-286 (C>T>A) A genotype polymorphism and specific IgG antibodies isotype levels can contribute to a reduced risk of EOS. Furthermore, CRP has a potential use in detecting EOS in neonates, which may mean earlier detection and management of EOS and subsequently better clinical outcome.

Anti-malarial IgG subclasses pattern and FcγRIIa (CD32) polymorphism among pregnancy-associated malaria in semi-immune Saudi women.

BACKGROUND: Pregnant women remain are at an increased risk of malaria with primigravidae being at the highest risk. Genetic polymorphism of the Fc receptor IIa for immunologlobulin (Ig) G (FcγRIIa) determines IgG subclass binding. Protection against pregnancy-associated malaria (PAM) is associated with the production of IgG specific for apical membrane antigen-1 (AMA-1). The present study was undertaken to examine the relationship between specific IgG/IgG subclasses and malaria infection. The second aim of the study is to examine the association between FcγRIIa R/H131 polymorphism in correlation with specific anti-malarial IgG antibodies of AMA-1 distribution and asymptomatic malaria infection among Saudi women living in the southern part of Saudi Arabia. METHODS: One hundred and twenty pregnant women living in an area of meso-endemic Plasmodium falciparum malaria infection were consecutively enrolled onto the study. These pregnant women were asymptomatic and attending routine antenatal clinics. The levels of plasma antibodies (IgG and subclasses AMA-1) were measured using indirect enzyme-linked immunosorbent assays (ELISA). Genotyping of FcγRIIa-R/H131 dimorphism was performed using gene-specific polymerase chain reaction (PCR) amplification with allele-specific restriction enzyme digestion (BstU1) of the PCR product. RESULTS: A total of sixty-two (52%) pregnant women was diagnosed with asymptomatic malarial infection (ASM) compared with 58 (48%) malaria free controls (MFC). In the ASM group, there were high levels of anti-malarial IgG1 and IgG3, when compared to MFC (P value <0.001, respectively). The FcγRIIa-R/R131 genotype and R131 were found to be statistically significantly more prevalent in the ASM group when compared to the MFC group [55% for ASM versus 12% for MFC, odds ratio (OR) 5.62, 95% confidence interval (CI)= (2.03- 15.58), P value= 0.001]. However, the H/H131 genotype showed statistically significant association with MFC [14% for ASM versus 50% for MFC, OR(0.36), 95% CI= (0.14- 0.95), P value= 0.03]. CONCLUSIONS: The study revealed that the ASM patients had higher anti-malarial IgG and IgG subclasses antibody levels when compared to the MFC. The FcγRIIa-R/R131 genotype and R131 allele were found to be statistically prevalent in the ASM when compared to the MFC group. The individuals carrying H/H131 were consistently associated with higher levels of anti-malarial IgG subclasses.

Design, synthesis, anti-schistosomal activity and molecular docking of novel 8-hydroxyquinoline-5-sufonyl 1,4-diazepine derivatives.

Schistosomiasis remains one of the most prevalent parasitic infections and has significant public health consequences. Praziquantel (PZQ) is the only drug currently administrated to treat this disease. However, praziquantel-resistant parasites have been identified in endemic areas and can be generated in the laboratory. Therefore, it is essential to find new therapeutics. Herein we report a series of novel 8-hydroxyquinoline-5-sufonyl 1,4-diazepine derivatives, which were synthesized, characterized and tested as anti-schistosomal agents in vitro. Among all tested compounds, compounds 4a, 5b, and 7b at different tested concentrations (50, 100, and 200 µg/mL) showed the highest schistosomicidal activity. Among those 3 compounds, compound 7b was the most potent anti-schistosomal one. Moreover, all tested compound, at 50 µg/mL concentration, significantly reduced oviposition of adult worms in vitro. Furthermore, both compound 4a and 7b, as well as compound 6a, completely diminished egg deposition. To clarify the possible mechanism by which novel 8-hydroxyquinoline-5-sufonyl 1,4-diazepine derivatives act as anti-schistosomal agents, molecular docking of all new compounds was carried out using Molsoft ICM pro 3.5-0a to investigate the binding affinity and binding mode to thioredoxin glutathione reductase enzyme (TGR), a potential drug target for anti-schistosomal agents. The docking results revealed moderate to high affinity of the new compounds towards TGR. Compound 7b scored the highest binding energy (-101.13 kcal/mol) against TGR crystal structure forming eight hydrogen bonds with the amino acid residues at the binding site of the receptor. This result indicates that compound 7b could exert its effect through inhibition of TGR, which is a vital enzyme for schistosome survival.

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.

Impact of petroleum industry on goats in Saudi Arabia: heavy metal accumulation, oxidative stress, and tissue injury.

Heavy metals (HMs) constitute a group of persistent toxic pollutants, and the petroleum industry is one of the sources of these metals. This study aimed to evaluate the levels of lead (Pb), cadmium (Cd), nickel (Ni), and vanadium (V) in Plantago ovata and milk and tissues of domestic goats in the eastern region of Saudi Arabia. Plant samples and blood, milk, muscle, liver, and kidney samples were collected from domestic goats and the levels of Pb, Cd, V, and Ni were determined. Liver and kidney tissue injury, oxidative stress, and expression of pro-inflammatory and apoptosis markers were evaluated. Pb, Cd, V, and Ni were increased in Plantago ovata as well as in milk, blood, muscle, liver, and kidney of goats collected from the polluted site. Aminotransferases, creatinine, and urea were increased in serum, and histopathological changes were observed in the liver and kidney of goats at the oil extraction site. Malondialdehyde and the expression levels of pro-inflammatory cytokines, Bax, and caspase-3 were increased, whereas cellular antioxidants and Bcl-2 were decreased in liver and kidney of goats at the polluted site. In conclusion, petroleum industry caused liver and kidney injury, oxidative stress, and upregulated pro-inflammatory and apoptosis markers in goats. These findings highlight the negative impact of petroleum industry on the environment and call attention to the assessment of its effect on the health of nearby communities.

Evaluation of a 14.5 kDa-Fasciola gigantica fatty acid binding protein as a diagnostic antigen for human fascioliasis.

The aim of the present study was to evaluate the efficiency of 14.5 kDa-Fasciola gigantica fatty acid binding protein (FABP) as a diagnostic antigen for human fascioliasis. 14.5 kDa FABP was isolated from the crude extract of adult F. gigantica worms by ion exchange chromatography followed by gel filtration chromatography and then analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis under reducing condition. Anti-FABP IgG polyclonal antibody (pAb) was generated in rabbits and purified by using sequential use of ammonium sulfate, caprylic acid, and then ion exchange chromatography. Conjugation of purified rabbit anti-FABP IgG with horse reddish peroxidase (HRP) was conducted and used in detecting the coproantigen in the stool and the circulating Fasciola antigen (CA) in the sera of Fasciola-infected patients using sandwich enzyme-linked immunosorbent assay (ELISA). The sensitivities of sandwich ELISA test were 96.43% and 94.74%, while the test specificities were 94.87% and 84.62% for the detection of coproantigen and CA, respectively. The parasitological diagnosis using the Kato-Katz technique revealed 64.29% sensitivity with 100% specificity. The diagnostic efficacy of sandwich ELISA was 95.52% for coproantigen and 87.93% for CA detection. In contrast, the diagnostic efficacy of Kato-Katz technique was 85.07%. It was concluded that 14.5 kDa FABP represented a valuable antigen for the immunodiagnosis of human fascioliasis using sandwich ELISA.

Heavy Metal Accumulation, Tissue Injury, Oxidative Stress, and Inflammation in Dromedary Camels Living near Petroleum Industry Sites in Saudi Arabia.

The petroleum industry can impact the environment and human health. Heavy metals (HMs), including lead (Pb), cadmium (Cd), nickel (Ni), and vanadium (V), are toxic pollutants found in petroleum that can cause several severe diseases. This study investigated the impact of the oil industry on the Arabian camel (Camelus dromedarius) in the eastern region of Saudi Arabia, pointing to HMs accumulation, tissue injury, redox imbalance, inflammation, and apoptosis. Soil and camel samples (milk, blood, muscle, liver, and kidney) were collected from a site near an oil industry field and another two sites to analyze HMs. Pb, Cd, Ni, and V were increased in the soil and in the camel's milk, blood, muscle, liver, and kidney at the polluted site. Serum aminotransferases, urea, and creatinine were elevated, and histopathological alterations were observed in the liver and kidney of camels at the oil industry site. Hepatic and renal lipid peroxidation, pro-inflammatory cytokines, Bax, and caspase-3 were increased, whereas cellular antioxidants and Bcl-2 declined in camels at the oil extraction site. In conclusion, the oil industry caused soil and tissue accumulation of HMs, liver and kidney injury, oxidative stress, and apoptosis in camels living close to the oil extraction site. These findings pinpoint the negative impact of the oil industry on the environment, animal, and human health.

Association between Pediatric Adenovirus Infection and Type 1 Diabetes.

BACKGROUND: Viruses are among the inducers of type 1 diabetes (T1D) as they are implicated in the initiation of ß-cell destruction. This study aimed to explore the link between adenoviruses' infection, inflammatory biomarkers, and the development of T1D. METHODS: The study population included 80 children with T1D and 40 healthy controls (2-16 years old). The T1D group was further clustered into two groups according to time of T1D diagnosis: a group of children who were diagnosed during the first year of life and a second group who were diagnosed after the first year of life. Adenovirus DNA, anti-adenovirus IgG, cytokines, and lipid profiles were screened in the different groups. The results were statistically assessed using one-way analysis of variance (ANOVA) and LSD t-test. RESULTS: Positive adenovirus PCR was detected in 2.5% and 20% of normal and T1D children, respectively. Moreover, the positive PCR results for adenovirus were found significantly higher in the T1D group, who were diagnosed during the first year of life (33.4%), in comparison to those diagnosed after the first year of life (12%). Anti-adenoviruses IgG was found in 12.5% and 40% of healthy controls and diabetic children, respectively. Seropositive results were found to be higher in newly diagnosed children (46.7%) in comparison to those previously diagnosed with T1D (36%). Body mass index (BMI), IFN-γ, IL-15, adiponectin, lipid profile, and microalbuminuria were significantly increased in T1D adenoviruses-positive children compared to children who were negative for adenoviruses. CONCLUSIONS: Adenovirus infection could be among the contributing risk factors and may play a role in the induction of T1D in children.