Parasitic Diseases Research Articles

Exploring potential inhibitors of acetylcholinesterase, lactate dehydrogenases, and glutathione reductase from Hagenia abyssinica (Bruce) J.F. Gmel. based on multi-target ultrafiltration-liquid chromatography-mass spectrometry and molecular docking.

Parasitic infections impose a significant burden on public health worldwide. European pharmacopoeia records and ethnopharmacological studies indicate that Hagenia abyssinica (Bruce) J.F. Gmel. has traditionally been used to treat a variety of parasitic infections, while the potential antiparasitic compounds remain ambiguous. Acetylcholinesterase (AChE), lactate dehydrogenases (LDH), and glutathione reductase (GR) are the key target enzymes in the survival of parasites. The aim of our work was to screen antiparasitic compounds targeting AChE, LDH, and GR from H. abyssinica. Ultrafiltration-liquid chromatography-mass spectrometry (UF-LC-MS) combined with molecular docking was used in this study. Therein, the alamarBlue® and Ellman's methods were employed to reveal the antitrypanosomal effect and AChE inhibitory activity. Meanwhile, the UF-LC-MS was carried out to screen the potential active compounds from H. abyssinica. Subsequently, molecular docking was performed to evaluate the binding mechanisms of these active compounds with AChE, LDH, and GR. Finally, the AChE inhibitory activity of potential inhibitors was detected in vitro. H. abyssinica exhibited significant antitrypanosomal and AChE inhibitory activity. Corilagin, brevifolin carboxylic acid, brevifolin, quercetin, and methyl ellagic acid were recognized as potential AChE inhibitors by UF-LC-MS, while methyl brevifolin carboxylate was identified as AChE, LDH, and GR multi-target inhibitor, with binding degree ranged from 20.96%-49.81%. Molecular docking showed that these potential inhibitors had a strong affinity with AChE, LDH, and GR, with binding energies ranging from -6.98 to -9.67 kcal/mol. These findings were further supported by the observation that corilagin, quercetin, brevifolin carboxylic acid, and methyl brevifolin carboxylate displayed significant AChE inhibitory activity compared with the positive control (gossypol, 0.42 ± 0.04 mM), with IC50 values of 0.15 ± 0.05, 0.56 ± 0.03, 0.99 ± 0.01, and 1.02 ± 0.03 mM, respectively. This study confirms the antiparasitic potential of H. abyssinica, supporting the traditional use of H. abyssinica in local ethnopharmacology to treat parasites. At the same time, corilagin, brevifolin carboxylic acid, brevifolin, quercetin, methyl ellagic acid, and methyl brevifolin carboxylate exert their anti-parasitic effects by inhibiting AChE, LDH, and GR, and they are expected to be natural lead compounds for the treatment of parasitic diseases.

A first insight into seropositivity of Neospora caninum and associated risk factors in free-roaming dogs from Ecuador.

Neosporosis is a worldwide parasitic disease caused by the protozoan Neospora caninum. It can cause economic losses to farmers due to its relationship with abortions and neonatal mortality in cows. Dogs play a key role in its spread as they are considered definitive hosts. In this study, we determined for the first time the seropositivity of N. caninum infection in dogs from Ecuador and evaluated potential risk factors. A total number of 339 free-roaming dogs from the three main regions of Ecuador (Coastal, Andean, and Amazonian regions) were included in the study and classified either as urban or rural dogs. Serum samples were collected from November 2018 to May 2019, and analyzed with a commercial ELISA test. An overall seropositivity of 6.8% (CI: 95%, 2.8% - 11.7%) was found in N. caninum infection with no statistical differences among regions or urban/rural dogs. This is the first surveillance of N. caninum in Ecuador, confirming a country-wide distribution of this pathogen. Considering the large populations of free-roaming dogs in Ecuador, a One Health approach for surveillance and managing N. caninum in dogs is needed to protect either livestock or wildlife.

Prevalence and Associated Risk Factors of Haemonchus contortus in Sheep Slaughtered at Bahir Dar Municipal Abattoir, Ethiopia

Haemonchus contortus is a blood sucking parasite resulting a massive economic loss in tropical and subtropical sheep rearing areas. A cross-sectional study was conducted to estimate the prevalence of haemonchosis and its predictors at Bahir Dar municipal abattoir, northwestern Ethiopia, from December 2022 to April 2023. A total of 378 abomasum of sheep were taken by using systematic random sampling and inspected according to standard procedures. Accordingly, the findings of this study revealed an overall prevalence of 34.40% (30/378) (95% CI: 29.75-39.35). The presence of H. contortus in female sheep (46.41%) was significantly higher than in male (23.35%) (P<0.001). The same is true; prevalence of haemonchosis in young (<1 year) sheep was 43.33% significantly (P<0.001) higher than that of adult (≥1 year) which was 26.26%. Based the origin of the animals in the current study, it was nonsignificant variation (P=0.386). The current study depicted that H. contortus infection is a common parasitic disease and requires remarkable attention to the prevention and control of haemonchosis at the study area.

A Comphrensive Review on Amoebiasis

With its wide range of dissemination, Entamoeba histolytica poses a serious threat in practically any nation where there is a regular barrier between human waste, food, and water sources. Except E. histolytica, at least eight distinct amoebas are thought to be commensals in the human intestinal lumen. As the second biggest cause of death from parasitic disease globally, the parasite poses a serious threat to public health in most regions of the world and has reemerged in several previously inactive locations. The majority of E. histolytica infections have very minor or no symptoms, however, colitis and liver abscesses brought on by amoebic infections are the most common clinical manifestations. Typically, a laboratory's diagnosis of amoebiasis is based on a microscope.

Evaluation of genotoxic damage, production reactive oxygen and nitrogen species in Plasmodium yoelii yoelii exposed to sodium metavanadate

Malaria represents the greatest global health burden among all parasitic diseases, with drug resistance representing the primary obstacle to control efforts. Sodium metavanadate (NaVO3) exhibits antimalarial activity against the Plasmodium yoelii yoelii (Pyy), yet its precise antimalarial mechanism remains elusive. This study aimed to assess the antimalarial potential of NaVO3, evaluate its genotoxicity, and determine the production of reactive oxygen and nitrogen species (ROS/RNS) in Pyy. CD-1 mice were infected and divided into two groups: one treated orally with NaVO3 (10 mg/kg/day for 4 days) and the other untreated. A 50% decrease in parasitemia was observed in treated mice. All experimental days demonstrated DNA damage in exposed parasites, along with an increase in ROS and RNS on the fifth day, suggesting a possible parasitostatic effect. The results indicate that DNA is a target of NaVO3, but further studies are necessary to fully elucidate the mechanisms underlying its antimalarial activity.

BCG activation of trained immunity is associated with induction of cross reactive COVID-19 antibodies in a BCG vaccinated population

Background Pakistan is endemic to a diverse set of parasitic, mycobacterial and viral diseases. The recognition of BCG Trained Immunity (TI) led us to postulate that the continued presence of BCG-TI may play a protective role, previously reported for both infectious and noninfectious conditions. Most of the previous studies have addressed the issue of BCG-TI in the paediatric populations. This study addressed the key issue of maintenance of BCG-TI in a wider age range (adolescent and adults) to identify the strength and quality of the immune responses. Objective To assess the BCG-induced recall responses in healthy individuals by cytokines secreted from the TI network and its potential role in providing cross-protection against COVID-19 and other viral infections. Study design In this cross-sectional study, healthy young adults and adolescents (n = 20) were recruited from 16–40 years of age, with no prior history of TB treatment, autoimmune, or chronic inflammatory condition. Methods BCG-induced cytokine responses were assessed using prototypic markers for cells of the TI network [macrophages [M1 (TNFα, IFNγ), M2 (IL10)], NK (IL2), Gamma delta (γδ) T (IL17, IL4)] and SARS CoV2 IgG antibodies against RBD using short-term (12 hrs.) cultures assay. Results Significant differences were observed in the magnitude of recall responses to BCG with macrophage cytokines showing the highest mean levels of TNFα (9148 pg/ml) followed by IL10 (488 pg/ml) and IFNγ (355 pg/ml). The ratio of unstimulated vs.BCG-stimulated cytokines was 132 fold higher for TNFα, 40 fold fo r IL10, and 27 fold for IFNγ. Furthermore, SARS-CoV-2 antibodies were also detected in unstimulated plasma which showed cross reactivity with BCG. Conclusion The presence of cross reactive antibodies to SARS-CoV-2 and the relative ratio of pro- and anti-inflammatory cytokines secreted by activated TI cellular network may play a pivotal role in protection in the early stages of infection as observed during the COVID-19 pandemic in the younger age groups resulting in lower morbidity and mortality.

Development and evaluation of time-resolved rapid immunofluorescence test for detection of TSOL18 specific antibody in porcine cysticercosis infections

BackgroundPorcine cysticercosis, a serious zoonotic parasitic disease, is caused by the larvae of Taenia solium and has been acknowledged by the World Organization for Animal Health. The current detection methods of Cysticercus cellulosae cannot meet the needs of large-scale and rapid detection in the field. We hypothesized that the immunofluorescence chromatography test strip (ICS) for detecting Cysticercus cellulosae, according to optimization of a series of reaction systems was conducted, and sensitivity, specificity, and stability testing, and was finally compared with ELISA. This method utilizes Eu3+-labeled time-resolved fluorescent microspheres (TRFM) coupled with TSOL18 antigen to detect TSOL18 antibodies in infected pig sera.ResultsICS and autopsy have highly consistent diagnostic results (n = 133), as determined by Cohen’s κ analysis (κ = 0.925). And the results showed that the proposed ICS are high sensitivity (0.9459) with specificity (0.9792). The ICS was unable to detect positive samples of other parasites. It can be stored for at least six months at 4℃.ConclusionsIn summary, we established a TRFM-ICS method with higher sensitivity and specificity than indirect ELISA. Results obtained from serum samples can be read within 10 min, indicating a rapid, user-friendly test suitable for large-scale field detection.

Discovery of 1,3,4-Oxadiazole Derivatives as Broad-Spectrum Antiparasitic Agents.

Vector-borne parasitic diseases (VBPDs) pose a significant threat to public health on a global scale. Collectively, Human African Trypanosomiasis (HAT), Leishmaniasis, and Malaria threaten millions of people, particularly in developing countries. Climate change might alter the transmission and spread of VBPDs, leading to a global burden of these diseases. Thus, novel agents are urgently needed to expand therapeutic options and limit the spread of drug-resistant parasites. Herein, we report the development of broad-spectrum antiparasitic agents by screening a known library of antileishmanial and antimalarial compounds toward Trypanosoma brucei (T. brucei) and identifying a 1,3,4-oxadiazole derivative (19) as anti-T. brucei hit with predicted blood-brain barrier permeability. Subsequently, extensive structure-activity-relationship studies around the lipophilic tail of 19 led to a potent antitrypanosomal and antimalarial compound (27), with moderate potency also toward Leishmania infantum (L. infantum) and Leishmania tropica. In addition, we discovered a pan-active antiparasitic molecule (24), showing low-micromolar IC50s toward T. brucei and Leishmania spp. promastigotes and amastigotes, and nanomolar IC50 against Plasmodium falciparum, together with high selectivity for the parasites over mammalian cells (THP-1). Early ADME-toxicity assays were used to assess the safety profile of the compounds. Overall, we characterized 24 and 27, bearing the 1,3,4-oxadiazole privileged scaffold, as broad-spectrum low-toxicity agents for the treatment of VBPDs. An alkyne-substituted chemical probe (30) was synthesized and will be utilized in proteomics experiments aimed at deconvoluting the mechanism of action in the T. brucei parasite.

Therapeutic potential of natural products in schistosomiasis-associated liver fibrosis

Therapeutic potential of natural products in schistosomiasis-associated liver fibrosis

High-intensity exercise training in large yellow croaker is a compromise between disease resistance and fish welfare

Exercise training is being applied to improving the productivity and welfare of farmed fish species. Nonetheless, research into whether exercise training improves disease resistance and immune function in fish is still at an early stage, and more studies is required. This study examined the impact of exercise training on growth performance, disease resistance and immune function of large yellow croaker (Larimichthys crocea). Juvenile fish underwent a 12 days training regime at 2–3 BL.s−1, followed by a parasite disease challenge test (Cryptocaryon irritans). Fish muscle RNA-seq analyses was used to evaluate the influence of exercise on juvenile immune function. The results showed that: (1) exercising at 2–3 BL.s−1 had no impact on the growth of juvenile croakers, however it induced an inflammatory response in croakers, leading to increased mortality in the treatment group (T) compared to the control group (C); (2) exercising also enhanced the resistance of T to C. irritans, resulting in a significant 17.6% increase in the survival rate of T compared to that of C; and (3) the RNA-seq analysis of the muscles demonstrated that differentially expressed genes (DEGs) between T and C were primarily involved in regulating the expression of genes related to muscle development and immunity in croaker; (4) enrichment analyses using KEGG and GO revealed that the DEGs were significantly enriched in pathways related to metabolic processes and biosynthesis. In conclusion, it is suggested that exercise training with high water speed induces an inflammatory response in the large yellow croaker, compromising the welfare of the fish. However, this stimulates the expression of immune-regulation-related genes and pathways, thereby improving the disease resistance of exercising individuals. Our study reveals that exercise training can improve disease resistance of large yellow croaker, which has significant implications for the sustainability of the croaker aquaculture industry.

Emerging and Reemerging Parasitic Diseases in Taiwan: A Retrospective Study of Clinical Case Reports in 2001~2018

Emerging and re-emerging parasitic diseases can cause significant economic burdens at national and global levels. However, governments often underestimate or ignore these diseases, especially in developed countries. This retrospective, case-oriented study analyzed parasitic diseases reported in Taiwan between 2001 and 2018. One hundred and thirty-two eligible clinical profiles of Taiwanese patients obtained from the NCBI, Scopus, Google Scholar, and Web of Science databases and local journals according to age, sex, source of infection, symptoms, risk factors, and geographical regions were analyzed. The analysis results showed that the number/frequency of cases caused by nematodes (46.97%) or protozoa (37.88%) was significantly higher than that of trematodes (9.85%) or cestodes (5.30%) (p < 0.0001). Northern Taiwan (46.97%) had a significantly higher rate than Southern Taiwan (33.33%), Central Taiwan (8.33%), and Eastern Taiwan (5.30%) (p < 0.05). The 15–65 age group (68.94%) had a significantly higher rate than the 65–90 age group (22.73%) and the 0–15 age group (8.33%) (p < 0.0001). Males (70.46%) had a significantly higher number/frequency of cases than females (29.54%) (p < 0.0001). People who acquired the infection through the food/soil route (32.58%) or who had a low immune status (32.58%) had a higher rate than travel-related infections (15.15%) (p < 0.001). The present study showed that emerging/reemerging parasitic infections continue to be of great concern to the lives and health of Taiwanese citizens and, if ignored, will threaten the health of the Taiwanese people; therefore, the delineation of preventive measures by health authorities is urgently warranted.

Infant Mortality in the Chechen Republic: Comparative Analysis and Major Trends

Background. Despite the clear trend towards infant mortality decrease in our country, there are significant differences in values in some federal districts and regions of Russian Federation. Thus, the assessment of infant mortality rates and health indicators is crucial topic of scientific analysis. Objective. The aim of the study is to investigate selected child health indicators and infant mortality rates in the Chechen Republic. Methods. We have conducted the retrospective cross-sectional study of infant mortality rates, prematurity incidence, infant and newborn morbidity, and mortality of children born sick or got sick. The study was based on the data from official statistics and from the extraction of statistical reporting forms No. 12 and No. 32. Results. The Chechen Republic belongs to the regions with high infant mortality rate, however, it has decreased by 11.6% from 6.9 to 6.1‰ in 2018–2022. The major diseases causing lethal outcomes in infants in this region, and in Russia as a whole, were certain conditions that occur in the perinatal period, and congenital disorders. Meanwhile, mortality from respiratory diseases and some infectious and parasitic diseases exceeded the national average. Prematurity incidence in the republic was 1.5 times lower than the national average, newborns morbidity was 1.7 times lower, infants morbidity was 4.0 times lower. Trend analysis has revealed that prematurity incidence and newborns morbidity have slightly changed over 5 years (+2.2% and –1.0%), while infants morbidity had significant trend (–40.2%). All morbidity rates of children who died at the age under 1 year were significantly lower than the national average for all classes of diseases that are the most common for infants mortality. The mortality rates among children born sick or got sick were on average 5.4 times higher than similar indicators in Russia. The highest mortality rate was observed among children who died from perinatal conditions, congenital disorders, external causes, and some infectious and parasitic diseases. The level of the maternal and child health service performance was 0.44 on average over the 5-year interval, that corresponds to the average level of efficacy. Conclusion. This study has allowed to reveal that there is an urge to improve the organization of medical care for infants in the Chechen Republic.

Epidemiological update of cystic echinococcosis in livestock and assessment of practices related to its control in the Mediterranean area

Cystic echinococcosis (CE), caused by the tapeworm Echinococcus granulosus, is a zoonotic parasitic disease that still represents a serious threat to human and animal health worldwide. The Mediterranean basin is recognized as one of the major hotspots of CE due to several factors, including the presence of diverse intermediate host species as well as socio-economic and cultural conditions of local communities. This study aims to take a closer look at epidemiological data on CE in the Mediterranean area and assess the knowledge attitudes and practices of shepherds towards this disease in four countries (Algeria, Greece, Italy and Tunisia), highly endemic for CE, with the final goal of identifying highly endemic risk areas and practices in use which might potentially allow the persistence of E. granulosus infection in these areas. To update the epidemiological scenario of CE in Mediterranean areas, a comprehensive review of peer-reviewed literature on CE prevalence data published during the 2017–2023 period was carried out and, through a geographical information system (GIS), a map displaying the current CE distribution in the Mediterranean area was generated. In addition, a questionnaire survey was conducted through in-depth interviews of the farmers to collect information on their management system as well as knowledge attitudes and practices towards CE. From the farmer-participatory survey some risky practices emerged including the non-regular deworming of dogs or the use of ineffective drugs or dosing, as well as the provision of uncooked animal viscera to dogs. Finally, lower levels of knowledge and awareness of the disease was observed among farmers from North Africa compared with those of European countries. In conclusion, the results obtained highlight that CE is still a very serious problem in Mediterranean areas and increased efforts are needed to promote awareness among farmers and to turn research results into policy in order to reduce the spread of this disease, according to the One Health perspective.

NKG2C+CD57+ natural killer with senescent features cells are induced in cutaneous leishmaniasis and accumulate in patients with lesional healing impairment.

Natural killer (NK) cells include different subsets with diverse effector capacities that are poorly understood in the context of parasitic diseases. Here, we investigated inhibitory and activating receptor expression on NK cells in patients with cutaneous leishmaniasis (CL) and explored their phenotypic and functional heterogeneity based on CD57 and NKG2C expression. The expression of CD57 identified NK cells that accumulated in CL patients and exhibited features of senescence. The CD57+ cells exhibited heightened levels of the activating receptor NKG2C and diminished expression of the inhibitory receptor NKG2A. RNA sequencing analyses based on NKG2C transcriptome have revealed two distinct profiles among CL patients associated with cytotoxic and functional genes. The CD57+NKG2C+ subset accumulated in the blood of patients and presented conspicuous features of senescence, including the expression of markers such as p16, yH2ax, and p38, as well as reduced proliferative capacity. In addition, they positively correlated with the number of days until lesion resolution. This study provides a broad understanding of the NK cell biology during Leishmania infection and reinforces the role of senescent cells in the adverse clinical outcomes of cutaneous leishmaniasis.

Effect of heatwaves on daily hospital admissions in Portugal, 2000–18: an observational study

Climate change has increased the frequency, intensity, and duration of heatwaves, posing a serious threat to public health. Although the link between high temperatures and premature mortality has been extensively studied, the comprehensive quantification of heatwave effects on morbidity remains underexplored. In this observational study, we assessed the relationship between heatwaves and daily hospital admissions at a county level in Portugal. We considered all major diagnostic categories and age groups (<18 years, 18-64 years, and ≥65 years), over a 19-year period from 2000 to 2018, during the extended summer season, defined as May 1, to Sept 30. We did a comprehensive geospatial analysis, integrating over 12 million hospital admission records with heatwave events indexed by the Excess Heat Factor (EHF), covering all 278 mainland counties. We obtained data from the Hospital Morbidity Database and E-OBS daily gridded meteorological data for Europe from 1950 to present derived from in-situ observations. To estimate the effect of heatwaves on hospital admissions, we applied negative binomial regression models at both national and county levels. We found a statistically significant overall increase in daily hospital admissions during heatwave days (incidence rate ratio 1·189 [95% CI 1·179-1·198]; p<0·0001). All age groups were affected, with children younger than 18 years being the most affected (21·7% [20·6-22·7] increase in admissions; p<0·0001), followed by the working-age (19·7% [18·7-20·7]; p<0·0001) and elderly individuals (17·2% [16·2-18·2]; p<0·0001). All 25 major disease diagnostic categories showed significant increases in hospital admissions, particularly burns (34·3% [28·7-40·1]; p<0·0001), multiple significant trauma (26·8% [22·2-31·6]; p<0·0001), and infectious and parasitic diseases (25·4% [23·5-27·3]; p<0·0001). We also found notable increases in endocrine, nutritional, and metabolic diseases (25·1% [23·4-26·8]; p<0·0001), mental diseases and disorders (23·0% [21·1-24·8]; p<0·0001), respiratory diseases (22·4% [21·2-23·6]; p<0·0001), and circulatory system disorders (15·8% [14·7-16·9]; p<0·0001). Our results provide statistically significant evidence of the association between heatwaves and increased hospitalisations across all age groups and for all major causes of disease. To our knowledge, this is the first study to estimate the full extent of heatwaves' impact on hospitalisations using the EHF index over a 19-year period, encompassing an entire country, and spanning 25 disease categories during multiple heatwave events. Our data offer crucial information to guide policy makers in effectively and efficiently allocating resources to address the profound health-care consequences resulting from climate change. None.

Fourteen-year trends in overweight, general obesity, and abdominal obesity in Amazonian indigenous peoples.

Available data show that the epidemiological profile of most indigenous Brazilian populations is characterized by the coexistence of long-standing health problems (high prevalence of infectious and parasitic diseases, malnutrition, and deficiency diseases, such as anemia in children and women of reproductive age), associated with new health problems, especially those related to obesity (hypertension, type 2 diabetes mellitus and dyslipidemia). Based on this scenario, this study analyzed the nutritional profile of the adult population of seven indigenous peoples from the Brazilian Amazon in the years 2007 and 2021. A total of 598 adults individuals were analyzed in 2007 (319 women and 279 men) and 924 in 2021 (483 women and 441 men), from seven indigenous peoples located in the state of Pará, who were assisted during health actions carried out in 2007 and in 2021. Body mass index classification used the World Health Organization criteria for adults: low weight, < 18.5kg/m2; normal weight, ≥ 18.5 and < 25kg/m2); overweight, ≥ 25 and < 30kg/m2, and obesity, ≥ 30kg/m2. A waist circumference (WC) < 90cm in men and < 80cm in women was considered normal. The data revealed heterogeneous anthropometric profiles, with a low prevalence of nutritional changes in the Araweté, Arara and Parakanã peoples, and high proportions of excess weight and abdominal obesity in the Kararaô, Xikrin do Bacajá, Asurini do Xingu and Gavião peoples, similar to or even higher than the national averages. Different stages of nutritional transition were identified in the indigenous peoples analyzed, despite apparently having been subjected to the same environmental pressures that shaped their nutritional profile in recent decades, which may indicate different genetic susceptibilities to nutritional changes. The evidence shown in this study strongly suggests the need to investigate in greater depth the genetic and environmental factors associated with the nutritional profile of Brazilian indigenous peoples, with assessment of diet, physical activity and sociodemographic and socioeconomic variables that enable the development of appropriate prevention and monitoring measures.

In silico analysis of soybean phytocompounds against Plasmodium falciparum

IntroductionNatural products have been indispensable since immemorial and still act as a supportive healer. Parasitic diseases are a significant hurdle for humans and are responsible for global morbidity and mass mortality. Due to the building up of resistance in parasites over existing drugs and the severe side effects of the drugs, there is an urgent need to explore various plant extracts to discover novel antiparasitic agents. This article deals with the pharmacological aspects of soybeans against Plasmodium falciparum, which causes many of the deadliest and most popular diseases, such as malaria. MethodsThe molecular basis for selective inhibition of soy phytoconstituents like beta-sitosterol, soya-saponin I, soya-saponin II, soya-saponin II methyl ester, dehydrosoyasaponin I, phytic acid, and tryptophyl leucine were evaluated using in silico molecular docking approaches and molecular dynamic simulations against the falcipain-2 (FP2) and phosphoethanolamine methyltransferase (PMT) of P. falciparum. ResultsThe results indicated that tryptophyl leucine exhibited potential inhibitory action against both enzymes based on pharmacophore, molecular docking, simulations, RMSD, RMSF, ADME and toxicity analyses. ConclusionMedicinal plants represent a treasure for bioactive lead compounds and eventually provide scope for further identification and investigation of novel drug candidates which may be important in the design of selective PfPMT/PfFP-2 inhibitors as potential antimalarials.

Andrographolide induced cytotoxicity and cell cycle arrest in Giardia trophozoites

Giardiasis is a prevalent parasitic diarrheal disease caused by Giardia lamblia, affecting people worldwide. Recently, the availability of several drugs for its treatment has highlighted issues such as multidrug resistance, limited effectiveness and undesirable side effects. Therefore, it is necessary to develop alternative new drugs and treatment strategies that can enhance therapeutic outcomes and effectively treat giardiasis. Natural compounds show promise in the search for more potent anti-giardial agents. Our investigation focused on the effect of Andrographolide (ADG), an active compound of the Andrographis paniculata plant, on Giardia lamblia, assessing trophozoite growth, morphological changes, cell cycle arrest, DNA damage and inhibition of gene expression associated with pathogenic factors. ADG demonstrated anti-Giardia activity almost equivalent to the reference drug metronidazole, with an IC50 value of 4.99 μM after 24 hours of incubation. In cytotoxicity assessments and morphological examinations, it showed significant alterations in trophozoite shape and size and effectively hindered the adhesion of trophozoites. It also caused excessive ROS generation, DNA damage, cell cycle arrest and inhibited the gene expression related to pathogenesis. Our findings have revealed the anti-giardial efficacy of ADG, suggesting its potential as an agent against Giardia infections. This could offer a natural and low-risk treatment option for giardiasis, reducing the risk of side effects and drug resistance.

Evaluating the Leishmania tarentolae response to inorganic strontium-based oxyfluorides

The increasing global prevalence of the parasitic vector-borne disease leishmaniasis combined with rising resistance to current therapeutics necessitates the search for novel approaches to combat leishmania. This study evaluates the effects of novel strontium-based oxyfluorides for potential therapeutic use by testing cultures of Leishmania tarentolae, a species of Leishmania found in reptiles, as a model species. Cells were cultured with a range of mixed metal strontium oxyfluoride compounds selected to systematically test the relationship between compound structure and cell viability and enzyme activity over time.

Role of cytokines in immunomodulation during malaria clearance.

Malaria remains a significant global health challenge, demanding a deeper understanding of host immune responses for effective clearance of the parasitic infection. Cytokines, as crucial mediators of the immune system, orchestrate a complex interplay during the various stages of malaria infection. Throughout the course of the disease, an intricate balance of pro-inflammatory and anti-inflammatory cytokines dictate the immune response's outcome, influencing parasitic clearance and disease severity. During the initial stages, interleukins such as interleukin-12 (IL-12), interferon-gamma (IFN-γ), and tumour necrosis factor-alpha (TNF-α) play pivotal roles in activating innate immune cells, initiating the anti-parasitic response. Simultaneously, regulatory cytokines like interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β) modulate this immune activation, preventing excessive inflammation and tissue damage. As the infection progresses, a delicate shift occurs, characterized by a transition to adaptive immunity, guided by cytokines like interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13), promoting antibody production and T-cell responses. Notably, the resolution of malaria infection crucially relies on a fine-tuned balance of cytokine networks. Dysregulation or imbalances in these mediators often result in immune hyperactivation, contributing to severe manifestations and prolonged infection. Understanding the multi-faceted roles of cytokines in malaria clearance offers promising avenues for therapeutic interventions. Targeting cytokine pathways to restore immune equilibrium or bolster protective responses could potentially enhance treatment strategies and vaccine development. In conclusion, the pivotal role of cytokines in immunomodulation during malaria clearance underscores their significance as potential targets for therapeutic interventions, offering promising prospects in the global fight against this infectious disease.