The anti-inflammatory properties of vinpocetine mediates its therapeutic potential in management of atherosclerosis.

Atherosclerosis (AS) formation is enhanced by different mechanisms including cytokine generation, vascular smooth muscle cell proliferation, and migration. One of the recent treatments towards endothelial dysfunction and AS is Vinpocetine (VPN). VPN is a potent inhibitor of phosphodiesterase enzyme 1 (PDE-1) and has anti-inflammatory and antioxidant effects through inhibition the expression of nuclear factor kappa B (NF-κB). VPN has been shown to be effective against the development and progression of AS. However, the underlying molecular mechanism was not fully clarified. Consequently, objective of the present review was to discuss the mechanistic role of VPN in the pathogenesis AS. Most of pro-inflammatory cytokines that released from macrophages are inhibited by action of VPN through NF-κB-dependent mechanism. VPN blocks monocyte adhesion and migration by constraining the expression and action of pro-inflammatory cytokines. As well, VPN is effective in reducing of oxidative stress a cornerstone in the pathogenesis of AS through inhibition of NF-κB and PDE1. VPN promotes plaque stability and prevents the erosion and rupture of atherosclerotic plaque. In conclusion, VPN through mitigation of inflammatory and oxidative stress, and improvement of plaque stability effects could be effective agent in the management of AS.

Serological and molecular detection of Toxoplasma gondii in ß. thalassemia patients.

Toxoplasma gondii is a worldwide opportunistic protozoan causing life-threatening infection in immunocompromised patients, while frequently asymptomatic in immunocompetent individuals. The current study aimed to detect T. gondii; serologically and molecularly in ß. thalassemia patients and evaluate the association of infection with some hematological parameters in these patients. Blood samples were collected from 100 ß. thalassemia patients. Serological diagnosis of T. gondii using ELISA for IgG and IgM antibodies was performed. Molecular diagnosis by Real-Time (RE) PCR was performed using specifically designed primers amplifying 389 bp fragments of Toxoplasma genome. 45 patients (45%) had anti-Toxoplasma IgG antibodies with no detectable IgM antibodies while both anti-Toxoplasma IgM and IgG antibodies were noticed in 10 patients (10%). IgM only antibodies were discovered in two cases (2%). The total seropositivity rate among patients was 57%. RE PCR analysis revealed Toxoplasma DNA in 20% out of 100 patients. PCR and serological examination showed slight agreement. A statistically significant relation was observed between the results of IgG and IgM ELISA and PCR for the detection of T. gondii infection among patients with ß. thalassemia. None of the studied risk factors (age, gender, contact with cats, consumption of undercooked meat) or hematological parameters (ESR, anemia degree, ferritin level, type of blood transfusion, spleen status) showed statistically significant association with Toxoplasma infection. It can be concluded that patients with thalassemia have a high risk of infection with T. gondii. RE PCR should be used as a diagnostic method in association with serology especially in immunocompromised patients to increase sensitivity.

Repurposing drugs to treat trichinellosis: in vitro analysis of the anthelmintic activity of nifedipine and Chrysanthemum coronarium extract.

Albendazole is the most common benzimidazole derivative used for trichinellosis treatment but has many drawbacks. The quest for alternative compounds is, therefore, a target for researchers. This work aims to assess the in vitro anthelmintic effect of nifedipine, a calcium channel blocker, and a methanol extract of the flowers of Chrysanthemum coronarium as therapeutic repurposed drugs for treating different developmental stages of Trichinella spiralis in comparison with the reference drug, albendazole. Adult worms and muscle larvae of Trichinella spiralis were incubated with different concentrations of the studied drugs. Drug effects were evaluated by parasitological and electron microscopic examination.As a result, the effects of these drugs on muscle larvae were time and dose-dependent. Moreover, the LC50 after 48 h incubation was 81.25 µg/ml for albendazole, 1.24 µg/ml for nifedipine, and 229.48 µg/ml for C. coronarium. Also, the effects of the tested drugs were prominent on adult worms as the LC50 was 89.77 µg/ml for albendazole, 1.87 µg/ml for nifedipine, and 124.66 µg/ml for C. coronarium. SEM examination of the tegument of T. spiralis adult worms and larvae showed destruction of the adult worms' tegument in all treated groups. The tegument morphological changes were in the form of marked swellings or whole body collapse with the disappearance of internal contents. Furthermore, in silico studies showed that nifedipine might act as a T. spiralis ß-tubulin polymerization inhibitor.Our results suggest that nifedipine and C. coronarium extract may be useful therapeutic agents for treating trichinellosis and warrant further assessment in animal disease models.

Efficacy of Nitazoxanide, Nitazoxanide-Garlic Combination and Tinidazole in Treatment of Giardia duodenalis and Blastocystis hominis: Coproscopic Assessment.

Background: Giardia duodenalis and Blastocystis hominis are among the most common intestinal protozoa worldwide. Treatment of infection by metronidazole (MTZ) has some limitations. The objective of this study was to detect the prevalence of Blastocystis and giardiasis among school-age children from December 2021 till March 2022 from Motoubes, Kafrelsheikh, Egypt, and determine the efficacy of nitazoxanide (NTZ), NTZ plus garlic and tinidazole (TIN) on Blastocystis and giardiasis infection. Methods: Stool samples were collected from 390 children and microscopically examined using formalin-ethyl acetate concentration and culturing on Jones' medium for B. hominis. Those who tested positive for giardiasis (120 children, 30.7%) (Group I) or Blastocystis (180 children, 46.1%) (Group II) were equally divided into four subgroups. The first subgroup received NTZ orally, every 12 hours for three successive days. The second subgroup received NTZ in the same dose as the first subgroup plus dry garlic powder every 12 hours for three successive days. The third subgroup received TIN as a single oral dose, and a fourth control subgroup. Successful cure was considered if no Blastocystis or giardiasis stages were found in post-treatment faecal specimens. Results: Cure rate was significantly higher in TIN treated groups (75.5% and 96.6%) than NTZ (57.7% and 40%) or NTZ plus garlic treated groups (55.5% and 43%) in both Blastocystis and giardiasis, respectively (P<0.05). Conclusion: TIN, once, is more efficacious than NTZ or NTZ plus garlic in the treatment of Blastocystis and giardiasis in children.

Immunological interactions in helminths-SARS CoV-2 coinfection: Could old enemy be a friend today?

Helminths are metazoan parasites affecting about one third of the worldwide population. Chronic helminth infections (CHIs) confer immunological tolerance to harmless and self-antigens mediated by regulatory T cells (Treg) that are up-regulated. In coronavirus disease 2019 (COVID-19), abnormal adaptive immune response and unrestrained innate immune response could result in local and systemic immune-mediated tissue damage. COVID-19 and CHIs establish complicated immune interactions due to SARS-CoV-2-induced immunological stimulation and CHIs-induced immunological tolerance. However, COVID-19 severity in patients with CHIs is mild, as immuno-suppressive anti-inflammatory cytokines counterbalance the risk of cytokine storm. Here, an overview of the interplay between helminths and COVID-19 severity is given. CHIs through helminth-derived molecules may suppress SARS-CoV-2 entry and associated hyperinflammation through attenuation of the TLR4/NF-kB signalling pathway. In addition, CHIs may reduce the COVID-19 severity by reducing the SARS-CoV-2 entry points at ACE2/DPP4/CD147 axis in the initial phase and immunomodulation in the late phase of the disease by suppressing TLR4/NF-kB signalling pathway.

Compound K: A systematic review of its anticancer properties and probable mechanisms.

Panax ginseng is a common natural product, which is well-known to have a wide range of pharmacological activities in cancer. Its metabolite, compound K (CK), has been reported to have anticancer activity. We aimed to systematically review the literature for evidence of anticancer effects of CK. We conducted a systematic search in eight databases. We included all in vitro and in vivo studies investigating the anticancer effects of CK with no restrictions. Quality assessment was applied by ToxRTool. Fifty-four articles were included in our study. The purity of CK in our included studies was at least 95%. The in vitro studies reported that CK had a potential anticancer activity on several cell lines including human lung cancer cell lines (A549, PC-9), nasopharyngeal carcinoma cell line (Hk-1), liver cancer cell line (BEL 7402), and pediatric acute myeloid leukemia cell lines (Kasumi-1, MV4-11). The in vivo studies reported a significant decrease in tumor volume in mice treated with CK. CK is a potential supplementary treatment in cancer chemotherapies. The safety and further clinical trials of CK should be explored for future drug development.

Evaluation of faecal lactoferrin as a morbidity biomarker in Schistosoma mansoni infection.

OBJECTIVE: Lactoferrin is an 80 KDa iron-binding glycoprotein that plays a significant role in the innate immune system and is considered to be an important microbicide molecule. This study aimed to assess the concentration of lactoferrin in Schistosoma mansoni-infected cases before and after praziquantel treatment. METHODS: A cross-sectional study was carried out on 250 individuals aged from 5 to 30 years. Stool samples were examined for the presence of parasitic infections using Kato-Katz and formalin ethyl acetate techniques. All S. mansoni-positive cases were treated with praziquantel and stool samples were recollected 21 days later. Faecal lactoferrin level was determined before and after treatment. RESULTS: The prevalence of S. mansoni infection was 14.4%. Among 36 participants infected with S. mansoni, the cure rate was 91.7%. A statistically significant difference in the mean lactoferrin level before and after treatment was detected (1648.95 pg/ml ± 656.5 vs. 1162.8 pg/ml ± 356.8). This difference was statistically significant in the middle and older age groups, in males and in the absence of coinfection with other parasites. CONCLUSION: Lactoferrin could be a promising biomarker associated with S. mansoni infection, however, it could not be used to assess the severity of infection.

Determinants of Schistosoma mansoni transmission in hotspots at the late stage of elimination in Egypt.

BACKGROUND: In certain settings, the prevalence and severity of schistosoma infection do not lessen despite repeated rounds of preventative chemotherapy; these areas are known as hotspots. This study aimed to investigate the role of human practices, besides environmental and malacological factors, in the maintenance of the Schistosoma mansoni infection transmission chain in hotspot areas in Egypt. METHODS: This cross-sectional study was conducted between July and November 2019 in Kafr El-Sheikh Governorate, Egypt. A pre-designed structured interviewing questionnaire was used to collect humanitarian data. Stool samples were collected from children aged 6-15 years on three successive days and examined using the Kato-Katz technique. Simultaneously, water and snail samples were taken from watercourses surrounding houses. Snails were identified based on their shell morphology and structure and tested for cercaria shedding. Water samples were analyzed for their physicochemical and biological characteristics. RESULTS: A total of 2259 fecal samples (1113 in summer and 1146 in fall) were collected from 861 children. About 46.9% of the participants were males, and 31.8% were aged 6-10 years. The prevalence of S. mansoni infection was higher during the summer than during the fall (19.1% vs 7.2%, respectively, P < 0.01). The intensity of infection (light, moderate, and heavy) during summer versus fall was (93.55 vs 89.38%, 6.45 vs 8.85%, and 0.00% vs 1.77%), respectively (P < 0.05). A higher prevalence of human infection was observed among males than females [OR = 1.63, 95% confidence interval (CI):1.10-2.40, P = 0.015], children aged 11-15 years than among their counterparts aged 6-10 years (OR = 2.96, 95% CI: 1.72-5.06, P < 0.001), and mothers with a low level of education (OR = 3.33, 95% CI: 1.70-6.52, P < 0.001). The main identified risk factors were contacting the main body of water-canal for washing clothes (OR = 1.81, 95% CI: 1.12-2.49, P = 0.015), land irrigation (OR = 2.56, 95% CI: 1.32-4.96, P = 0.004), water collection (OR = 2.94, 95% CI: 1.82-4.73, P < 0.001), bathing (OR = 2.34, 95% CI: 1.21-4.31, P = 0.009), and garbage disposal (OR = 2.38, 95% CI:1.38-4.12, P < 0.001). The count of Biomphalaria alexandrina was distinct between seasons (P < 0.01) in consistent with statistically significant differences in water temperature, salinity, turbidity, the total concentration of coliforms, depth, velocity, and water level (P < 0.01). The presence of grasses and duckweeds was significantly associated with snail infection (P = 0.00 l). Significant effects of water depth, pH, temperature, and total dissolved solids on snail count were also observed (P < 0.05). CONCLUSIONS: The persistence of the infection is due to adoption of risky behaviors and environmental factors that enhance snail survival and infection. Schistosomiasis elimination in hotspots requires an integrated control approach that combines preventive chemotherapy with other complementary measures.

P entatrichomonas hominis and other intestinal parasites in school-aged children: coproscopic survey.

Pentatrichomonas hominis (P. hominis) is a large intestinal flagellated protozoan infecting humans. Little is known about the epidemiology of P.hominis in Egypt, its association with gastrointestinal symptoms and the co-infection with other parasites. Demographic and clinical data were collected from 180 school-aged children. Parasitological examination of fecal samples was done using direct wet mount, formalin ethyl-acetate, Kato-Katz and cultivation on Jones' medium to detect P. hominis and associated parasitic infection. The diagnosis of P. hominis was confirmed using Giemsa stain and scanning electron microscopy. The prevalence of P. hominis was 13.8% (25 out of 180 children). The prevalence of parasitic co-infection was significantly higher in P. hominis infected (84%, 21 participants) than in non-infected children (56%, 87 participants). The presence of abdominal pain and diarrhea in P. hominis infected children was higher than in non-infected children (84% and 32% vs. 76% and 18%), respectively. The difference was not statistically significant. This is the first report of P. hominis in Egypt. The significant association between P. hominis and other intestinal parasites need more investigations. Further studies are needed to understand the epidemiology and pathogenicity of P. hominis.

Comparison of gdh polymerase chain reaction-restriction fragment length polymorphism and tpi assemblage-specific primers for characterization of Giardia intestinalis in children.

Background: Giardia is a diarrheagenic eukaryotic parasite that consists of at least eight morphologically identical but genetically distinct genotypes. Human giardiasis is caused mainly by A and B assemblages. Aim and objectives: The study aimed to compare the performance of gdh polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and tpi assemblage-specific primers in genotyping of G. intestinalis. Materials and Methods: Stool samples of 315 children were microscopically screened for G. intestinalis. Positive samples were genotyped using tpi assemblage-specific primers and gdh semi-nested PCR-RFLP techniques. Results: The prevalence of Giardia was 18.1%. The detected genotypes using tpi and gdh approaches were assemblage A (15.8% vs. 12.7%) and assemblage B (36.8% vs. 74.5%) as single infections and mixed assemblages A and B (47.4% vs. 12.7%). The two approaches showed a moderate agreement (kappa index = 0.413, P < 0.001). PCR-RFLP of gdh gene revealed that sub-assemblages BIII and BIV were equally detected (30.9% each). The remaining samples were equally divided between sub-assemblage AII, mixed BIII and BIV, and mixed AII and BIII (12.7% each). A significant association was detected between the retrieved sub-assemblages and the presence of symptoms. Conclusions: Although both approaches confirmed the predominance of assemblage B, the use of assemblage-specific primers is more effective in elucidating the true picture of mixed assemblage infection.

Evaluation of COVID-19 protease and HIV inhibitors interactions.

The epidemic of the novel coronavirus disease (COVID-19) that started in 2019 has evoked an urgent demand for finding new potential therapeutic agents. In this study, we performed a molecular docking of anti-HIV drugs to refine HIV protease inhibitors and nucleotide analogues to target COVID-19. The evaluation was based on docking scores calculated by AutoDock Vina and top binding poses were analyzed. Our results suggested that lopinavir, darunavir, atazanavir, remdesivir, and tipranavir have the best binding affinity for the 3-chymotrypsin-like protease of COVID-19. The comparison of the binding sites of three drugs, namely, darunavir, atazanavir and remdesivir, showed an overlap region of the protein pocket. Our study showed a strong affinity between lopinavir, darunavir, atazanavir, tipranavir and COVID-19 protease. However, their efficacy should be confirmed by in vitro studies since there are concerns related to interference with their active sites.

Detection of Giardia intestinalis assemblages A and B among children from three villages in the West Delta region, Egypt using assemblage specific primers.

Giardia intestinalis is a common diarrheagenic parasite infecting children globally. It has been classified into eight morphologically identical but genetically distinct genotypes. Human infection is mainly associated with A and B assemblages with variable geographical distribution. The present work aimed to study the epidemiology of assemblages A and B in children inhabiting different areas in Lower Egypt. Stool samples were collected from 315 children and examined microscopically for parasitic infections. Giardia positive samples were genotyped using tpi assemblage specific primers. The prevalence of Giardia was 18.1% among the examined children. Mixed assemblages A and B was more common (47.4%) than single assemblage B (36.8%) or A (15.8%). The distribution of different genotypes was significantly associated with the residence area, animal contact, and handwashing habits. A non-significant association was observed between Giardia assemblages and the clinical manifestations. Assemblage B is the predominant genotype among Egyptian children. The distribution of different Giardia assemblages is strongly associated with the studied area and the habits of its people.

Detection and molecular identification of Blastocystis isolates from humans and cattle in northern Egypt.

Blastocystis is one of the less well-understood waterborne protozoa of medical and veterinary importance. The present study aimed to detect, identify, and subtype Blastocystis in cattle and humans in northern Egypt and to investigate the potential for zoonotic transmission. Fecal samples were collected from 136 humans (68 in contact with animals and 68 no animal contact) and 190 cattle from a rural area in Kafr El-Sheikh Province, Egypt. All samples were microscopically examined by direct wet mount technique and cultured in Jones' medium. Genomic DNA was extracted from positive cultures. A region of the Blastocystis small subunit ribosomal ribonucleic acid (SSU rRNA) gene was amplified using PCR. Blastocystis subtypes were identified by sequencing of the amplified SSU rRNA gene. The relatedness of sequence types obtained in this study and others submitted in GenBank was compared according to their genetic relatedness. Out of 136 human and 190 cattle samples, Blastocystis was detected in 53 (38.9%) and 37 (19.4%), respectively using either culture or direct wet mount. Blastocystis SSU rRNA gene was amplified in 55 samples (32 humans and 23 animals). Six subtypes were identified (STs 1-3 in humans and ST4, ST10 and ST14 in cattle) and were distinguishable with inter (up to 0.075) and intra (up to 0.024) subtype variations. A close phylogenetic relationship between human and animal isolated STs 1-4 was demonstrated. To the best of our knowledge, this is the first study to investigate the the potentiality for zoonotic transmission of certain Blastocystis subtypes in northern Egypt.

A study on positive school children as indicators of schistosomiasis status in their families.

This study aimed to evaluate schistosomiasis positive school children as indicators of infection in their families. Four hundred and sixteen stool samples of children from two primary schools were examined microscopically for Schistosoma mansoni (S. mansoni) after Kato-Katz. Equal numbers from families of schistosomiasis positive and negative school children were examined by Kato-Katz. Circulating cathodic antigen (CCA) cassette test was performed on 100 Kato-Katz negative children to detect missed S. mansoni cases if any. S. mansoni infection rates among the primary school children were 15.3% and 1.6% in high and low prevalence schools respectively. Sixty five percent of school children had light intensity infection. Family members were either negative or exhibited a prevalence rate as low as 5-6% whether related to positive or negative children. A higher infection rate of S. mansoni was detected by the CCA test compared to the Kato-Katz. Conclusively, children can be good indicators of their particular families in areas of limited resources and low endemicity. Efforts are required to permit large scale use of CCA cassette test.

Intestinal parasites among humans and their livestock animals in a rural community in Gharbia governorate, Egypt.

Our objective was to study the prevalence of intestinal parasitic infections among humans and their contact livestock animals in a rural community in Gharbia governorate, Egypt. The collected human and livestock animal fecal samples were examined by formol ether sedimentation technique and modified Ziehl-Neelsen stain. Human samples were further examined by the Kato-Katz technique. The total prevalence of intestinal parasites in humans was 52.3%; 7.3% helminths and 45% protozoa. Regarding animals, 29% of livestock animals had protozoan parasites and no helminths were detected. Results revealed that risk factors including drinking tap water and attendance of nurseries, affected the rate of parasitic infection among humans. The infection rate of protozoa was significantly higher among humans (1.5 times) as compared to animals.

Prevalence and associated factors of asymptomatic leishmaniasis: a systematic review and meta-analysis.

Asymptomatic leishmaniasis is believed to play important role in maintaining the transmission of Leishmania spp. within endemic communities. Therefore, the efforts to eliminate leishmaniasis are daunting if we cannot manage asymptomatic leishmaniasis well. To clarify the global prevalence and factors associated with the asymptomatic Leishmania infection, we assessed the prevalence of asymptomatic leishmaniasis by a systematic review followed by meta-analyses. In addition, factors associated with the asymptomatic leishmaniasis versus symptomatic were also analyzed. We included all of the original articles alluding to the human asymptomatic leishmaniasis that was confirmed by at least one laboratory diagnosis method regardless of age, sex, race, and ethnicity of the patients, study design, publication date or languages. In total, 111 original articles were chosen for the data extraction. Based on our meta-analyses of the original articles reporting asymptomatic leishmaniasis mostly in endemic areas, the prevalence of asymptomatic leishmaniasis was 11.2% [95% confidence interval (CI) 8.6%-14.4%] in general population, 36.7% [95% CI 27.6%-46.8%] in inhabitants living in the same or neighboring household to the symptomatic patients, and 11.8% [95% CI 7.1%-19%] in HIV infected patients. Among individuals with leishmaniasis, 64.9% [95% CI 54.7%-73.9%] were asymptomatic and males were more susceptible to develop symptoms, with OR=1.88, 95% CI 1.19-2.99, P=0.007. Meta-regression analysis showed no significant change in the prevalence of asymptomatic leishmaniasis during the last 40 years.

Comparison among FLOTAC, Kato-Katz and formalin ether concentration techniques for diagnosis of intestinal parasitic infections in school children in an Egyptian rural setting.

The study aimed to compare the diagnostic performance of the Kato-Katz, formalin ether concentration method (FECM) and FLOTAC using Sheather's sugar solution (FS1), saturated sodium chloride (FS2) and zinc sulfate (FS7) for the diagnosis of intestinal parasites among school children, focusing on Schistosoma mansoni. Ninety fecal samples were examined using the above mentioned techniques. The overall infection rate was 87.7%. Concerning protozoa, FLOTAC (FS1 and FS2) and FECM detected nearly equal infection rates (43.3% and 44.4%, respectively) with very good agreement. Kato-Katz diagnosed the highest helminthic infection rate (57.8%) followed by FLOTAC FS7 (44.4%) and FECM showed the lowest helminthic infection rate (27.7%). As for S. mansoni, Kato-Katz showed an infection rate of 38.8% vs FLOTAC (22.2%) and FECM (11.1%). The three techniques detected the same infection rate (11.1%) with egg counts more than 72 eggs/gram of feces. The FLOTAC sensitivity and accuracy for the diagnosis of protozoa were 97% and 99%, respectively. Regarding helminths diagnosis, FLOTAC technique showed higher sensitivity (77%) and accuracy (87%) compared to FECM (48% sensitivity and 70% accuracy). Therefore, FLOTAC can be used synchronously or in replacement to other diagnostic techniques. This can strategically impact future control programmes of intestinal parasitic infections in limited resources settings.