Exploring NFκB pathway as a potent strategy to mitigate COVID-19 severe morbidity and mortality.

The pandemic of coronavirus disease 2019 (COVID-19), for which there does not appear to be an approved cure, the primary treatment options consist of non-pharmacological preventive measures and supportive treatment that are aimed at halting the progression of the disease. Nuclear factor kappa B (NFkB) presents a promising therapeutic opportunity to mitigate COVID-19-induced cytokine storm and reduce the risk of severe morbidity and mortality resulting from the disease. However, the effective clinical application of NFkB modulators in COVID-19 is hampered by a number of factors that must be taken into consideration. This paper therefore explored the modulation of the NFB pathway as a potential strategy to mitigate the severe morbidity and mortality caused by COVID-19. The paper also discusses the factors that form the barrier, and it offers potential solutions to the various limitations that may impede the clinical use of NFkB modulators against COVID-19. This paper revealed and identified three key potential solutions for the future clinical use of NFkB modulators against COVID-19. These solutions are pulmonary tissue-specific NFkB blockade, agents that target common regulatory proteins of both canonical and non-canonical NFkB pathways, and monitoring clinical indicators of hyperinflammation and cytokine storm in COVID-19 prior to using NFkB modulators.

Anti-Toxoplasma IgG Level in Type 2 Diabetic Patients: Does It Affect Glycemic Control?

Toxoplasma gondii (T. gondii) is an important opportunistic parasite which can leads to severe complications, even death in immuno-deficient patients. Diabetes is a systemic disease; considers an important factor that increases susceptibility and risk of various infections in the host by affecting the host's immune system. The aim of the current study was to determine possible relations between toxoplasma IgG antibodies titer and the level of glycemic control and vascular complications in type 2 diabetic patients. In this case control study, serum for 122 samples was analyzed using ELISA for the presence of anti-Toxoplasma- IgG-antibodies (Abs) in both type 2 diabetic patients (62) and controls (60). A1c titer (level of diabetic control) was estimated in all diabetic cases. Full history and examination were performed after all contributors' consents. Anti-Toxoplasma IgG-Abs were detected in 56.45 % of diabetic patients and in 36.67% of the controls. Toxoplasmosis was significantly found more prevalent in diabetics associated with hypertension than controls (P=0.005). Among diabetics, patients with positive anti T. gondii IgG have significant long duration of diabetes versus those with negative anti T. gondii IgG (7.14±2.962 vs.3.26±1.583 years, respectively; P < 0.001). No relations were found between types of diabetic vascular complication, level of glycemic control based on HbA1c level and occurrence of toxoplasmosis. We concluded that despite of high prevalence of anti T. gondii IgG in diabetic patients, it has no relation to diabetic complication and glycemic control.

Genotyping of Giardia duodenalis in children in upper Egypt using assemblage- specific PCR technique.

Giardia duodenalis is a common gastrointestinal protozoan parasite, causing diarrheal illness in humans worldwide. Yet, the distribution of G. duodenalis genotypes among human patients and their clinical relevance remains controversial. This study aimed to detect G. duodenalis in children in Upper Egypt and identify causative genotypes and elucidate a possible correlation between genotype and clinical presentation. One hundred sixty-five children, regardless of symptoms, were tested for giardiasis. Giardia positive stool samples (40/165) were subjected to PCR amplification targeting the tpi gene with positive PCR results in only 35 cases (87.5%). Assemblage-specific amplification of genotypes (A, B, and the zoonotic E strains) revealed predominantly G. duodenalis Assemblage A (45.7%). Assemblage B and mixed A and B infections were detected in 31.4% and 22.8% of children, respectively. Assemblage E was not detected. G. duodenalis assemblage A was dominant in children who complained of diarrhea and abdominal cramps. In contrast, asymptomatic children with positive stool samples display a higher frequency of assemblage B and mixed infections. The study highlights the predominance of Giardia Assemblage A in our study locality. This study is the first for this endemic area to use the copro-PCR technique for diagnosis and genotyping of giardiasis. Study results show the value of simple species-specific primers for genotyping in communities with little access to laboratory resources. Further genetic studies are needed to clarify the association between parasite genetic diversity and patient symptomatology.

Reliability of heterophyid antigens in heterologous protection against human schistosomiasis.

Schistosomiasis is a neglected tropical parasitic disease which has been controlled by praziquantel for many decades; however, reemergence of praziquantel resistant strains has been a continuous threat. Therefore, the development of reliable antischistosomal vaccine is significantly demanded for optimal control. In the present study, comparison among Schistosoma haematobium, Schsitosoma mansoni and Pygidiopsis genata crude antigens was carried out by Sodium dodecyl sulphate polyacrylamide gel electrophoresis. Hyperimmunization of rabbits with tested parasites' crude antigens was done to obtain hyperimmune sera. Western blotting was applied to show cross reactivity between parasites' crude antigens and either homologous or heterologous sera. Although there was no cross reaction between P. genata crude antigens and sera of both Schistosoma species and vice versa; it is supposed that the immunogenic band at 79 kDa might develop cross reactivity with Schistosma spp. SEA fractionation if used in future studies.

Eugenol, a potential schistosomicidal agent with anti-inflammatory and antifibrotic effects against Schistosoma mansoni, induced liver pathology.

INTRODUCTION: Schistosomiasis is one of the most prevalent parasitic infections in developing countries. Although chemotherapy is one of the main strategies in controlling the disease, it is less effective in reversal of schistosome-induced pathology especially in the chronic and advanced stages of schistosomiasis. New strategies and prospective therapeutic agents with antifibrotic effects are needed. Eugenol has a wide anti-inflammatory effect. In the present study, we investigated the possible antischistosomal effect of eugenol on Schistosoma mansoni. MATERIALS AND METHODS: The murine model of S. mansoni was established in three groups of adult male Balb-c mice; group I (infected non-treated group) and groups II and III (infected groups) treated orally with eugenol and praziquantel (PZQ), respectively. The expression of the sensitive immunohistochemical marker α-smooth muscle actin (α-SMA) in schistosome-infected tissues was determined. In addition, parasitological, biochemical, and histological parameters that reflect disease severity and morbidity were examined. RESULTS: Eugenol treatment showed significant reduction in total worm burden by 19.2%; however, the oogram pattern showed no marked difference compared to that of the PZQ group. Yet, eugenol significantly reduced the serum levels of hepatic enzymes: aspartate aminotransferase and alanine aminotransferase. Histopathological examination revealed a significant reduction in both numbers and diameters of hepatic granulomata, which was consistent with reduction in collagen fiber deposition. Additionally, the antifibrotic effect of eugenol was validated by its considerable reduction in the expression of the sensitive marker α-SMA in both eugenol- and PZQ-treated groups. CONCLUSION: Although eugenol could not totally eradicate adults of S. mansoni, the significant amelioration of liver enzymes and hepatic fibrosis potentiate eugenol's role as a promising antifibrotic and a complementary antischistosomal agent.

Peripheral brain-derived neurotrophic factor is reduced in stroke survivors with cognitive impairment.

Stroke presents a huge burden both globally and locally. Very few studies have evaluated cognitive impairment following stroke in Africa. This study evaluated cognitive impairment in stroke survivors and examined its relationship with peripheral blood levels of brain-derived neurotrophic factor (BDNF). It is hypothesized that serum BDNF levels significantly correlate with cognitive impairment. Cognition was assessed in 47 stroke survivors and 35 normal subjects using the Mini Mental State Examination (MMSE). Serum BDNF concentrations were determined using BDNF ELISA kits. Data were expressed as median (10th-90th percentiles) and analysed using non-parametric tests on SPSS statistics. The stroke survivors and controls were middle aged (in their fifties), with a median stroke duration of 10 months. The MMSE scores were significantly different between the stroke survivors and controls. The difference in serum BDNF values for the stroke survivors and controls was also statistically significant. About three quarters of the stroke survivors had mild or moderate cognitive impairment, which had a moderate positive relationship with serum BDNF levels. Our conclusion is that the very high prevalence of cognitive impairment observed during the period 10 months post stroke was associated, not with any of the socio-demographic factors in the subjects studied, but rather with reduced levels of brain-derived neurotrophic factor in the peripheral blood of stroke survivors.

Anti-giardial therapeutic potential of dichloromethane extracts of Zingiber officinale and Curcuma longa in vitro and in vivo.

Giardiosis is one of the common parasitic diarrhoea in humans, especially in children, worldwide. Many drugs are used for its treatment, but there is evidence of drug resistance, insufficient efficacy and unpleasant side effects. Natural products are good candidates for discovering more effective anti-giardial compounds. This study evaluated the activity of extracts of Zingiber officinale (ginger) and Curcuma longa (curcumin) against Giardia lamblia in vitro and in vivo. Giardia cyst suspension was prepared from children faecal specimens. For the in vitro experiment, 1, 10 and 50 mg/mL dichloromethane extracts of ginger and curcumin separately were incubated with Giardia cysts for 5, 10, 30 and 60 min. The viability was distinguished by 0.1 % eosin and a haemocytometer. For the in vivo experiments, Balb/c mice were infected with Giardia cyst suspension containing 10,000 cysts/mL. Infected mice were administered 10 and 20 mg kg(-1) day(-1) ginger and curcumin extracts separately for 7 days post-infection. The effectiveness of the extracts was evaluated by faecal cyst and intestinal trophozoite counts and histopathological examination of the small intestine. In vitro ginger extract had a higher significant effect on cyst viability than curcumin, in a dose- and time-dependent manner. In vivo ginger (more effective) and curcumin extracts significantly treated infected mice, and this was evidenced by the faecal cyst and intestinal trophozoite counts reduction, in addition to evident improvement of intestinal mucosal damages induced by Giardia infection. Z. officinale and C. longa extracts may represent effective and natural therapeutic alternatives with low side effects and without drug resistance in the treatment of giardiosis.