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Simple Summary: Fasciolosis is a parasitic disease of livestock causing important economic losses worldwide, and it is also a zoonosis. The treatment is based on the use of anthelmintic drugs, but the increase in resistance and the risk of drug residues in food make this approach no longer sustainable. Developing protective vaccines for the control of fasciolosis is postulated as an appropriate treatment, but a better knowledge of the host–parasite interaction is needed. The aim of the present study was to evaluate the hepatic lesions in sheep infected and reinfected with Fasciola hepatica during the acute and chronic stages of infection and the characterization of the hepatic inflammatory infiltrates using immunohistochemistry with CD3, Foxp3, iNOS, and CD163 antibodies. The most remarkable histopathological finding was the presence of large necrotic foci and/or hemorrhages adjacent to enlarged bile ducts containing adult parasites, suggesting flukes may have caused these lesions while feeding. In the literature, necrotic foci/hemorrhages are considered a consequence of parasite migration. In both the primoinfected and reinfected groups, and during acute and chronic stages of the infection, an increase in Foxp3 T cells with respect to uninfected controls and a poor expression of iNOS was found accompanied by a strong expression of CD163, suggesting a marked M2 activation of macrophages in the hepatic lesions. Fasciolosis is an important economic disease of livestock. There is a global interest in the development of protective vaccines since the current anthelmintic therapy is no longer sustainable. A better knowledge of the host–parasite interaction is needed to design effective vaccines. To date, few studies have evaluated host–parasite interaction by comparing infected and reinfected animals. The present study evaluates the microscopical hepatic lesions in sheep infected and reinfected with Fasciola hepatica during the acute and chronic stages of infection. The histopathological study revealed the presence of necrotizing foci (NF1) associated with larvae migration during the early stages of infection in the primoinfected (PI) and reinfected (RI) groups. In the late stages of infection of the PI group and at the early and late stages of infection in the RI groups, extensive necrotizing/hemorrhagic foci (NF2) were found in the vicinity of enlarged bile ducts, some containing adult flukes, suggesting parasites may have caused NF2 while feeding. The immunohistochemical study revealed an increase in Foxp3+ T cells in both PI and RI groups with respect to the UC group and in the infiltrates adjacent to NF1 in the RI groups with respect to the PI group, suggesting the F. hepatica induce Foxp3 T cell expansion to facilitate parasite survival. In addition, in both the PI and RI groups, and during acute and chronic stages of the infection, a poor expression of iNOS was found accompanied by a strong expression of CD163, suggesting a marked M2 activation of macrophages in the hepatic lesions, which may be related with healing processes, and it also may facilitate parasite survival. The main differences between PI and RI animals were the more severe infiltration of eosinophils and Foxp3+ T cells, whereas RI did not modify M2 activation of macrophages which occurs since the early stages of primoinfection. [ABSTRACT FROM AUTHOR]

Gene expression for Th1/Th2 cytokines (IL-4 and IFN-ɣ), regulatory cytokines (TGF-β and IL-10) and the transcriptional factor FoxP3 was analyzed in the liver and hepatic lymph nodes (HLN) from sheep immunized with partially protective and non-protective vaccine candidates and challenged with Fasciola hepatica. FoxP3 T cells were also evaluated by immunohistochemistry (IHQ). The most remarkable difference between the partially protected vaccinated (V1) group and the non-protected vaccinated (V2) group was a more severe expansion of FoxP3 T cells recorded by IHQ in both the liver and HLN of the V2 group as compared to the V1 group, whereas no differences were found between the V2 group and the infected control (IC) group. Similar results were recorded for FoxP3 gene expression although significant differences among V1 and V2 groups were only significant in the HLN, while FoxP3 gene expression was very similar in the V2 and IC groups both in the liver and HLN. No significant differences for the remaining cytokines were recorded between the V1 and V2 groups, but in the liver the V2 group shows significant increases of IFN-ɣ and IL-10 as compared to the uninfected control (UC) group whereas the V1 group did not. The lower expansion of FoxP3 T cells and lower increase of IFN-ɣ and IL-10 in the partially protected vaccinated group may be related with lower hepatic lesions and fluke burdens recorded in this group as compared to the other two infected groups. The most relevant change in regulatory cytokine gene expression was the significant increase of TGF-β in the liver of IC, V1 and V2 groups as compared to the UC group, which could be related to hepatic lesions. [ABSTRACT FROM AUTHOR]

Aims: A cross‐sectional study was carried out to assess the seroprevalence and risk factors associated with Trichinella spp. exposure in wild boar and Iberian domestic pigs from Mediterranean ecosystems of southwestern Spain. Methods and Results: Serum samples from 1360 wild boar and 439 Iberian domestic pigs were obtained during 2015–2020, from regions where Iberian pigs are raised under extensive conditions, hence sharing habitat with wild boar. Seropositivity was found in 7.4% (100/1360; 95% CI: 6.1–8.9) of the wild boar analysed. In this species, the individual seroprevalence ranged from 3.6% (8/223) (hunting season 2016–2017) to 11.4% (37/326) (2018–2019). A significant higher seropositivity was observed during the hunting season 2018–2019 (p < 0.009: OR = 3.07; 95% CI = 1.32–7.18) and one statistically significant cluster was detected within the studied area, in south central Andalusia [Relative Risk (RR) = 2.9; p = 0.037]. Females showed a significantly higher seroprevalence than males (8.7% vs. 5.8%) (p < 0.001: OR = 1.58; 95% CI = 1.08–2.32). No seropositivity to Trichinella spp. was detected in Iberian domestic pigs (0.0%; 95% CI: 0.0–0.9). Conclusions: Although wild boar play an important role as a reservoir of Trichinella sp. in the Mediterranean ecosystems of southwestern Spain, our results suggest that the wild boar production system does not seem to pose a risk of Trichinella exposure to domestic pigs, despite sharing habitats in these ecosystems. [ABSTRACT FROM AUTHOR]

Simple Summary: The systematic use of different antiparasitic products over time has led to several problems, such as drug resistances and biodiversity loss, which directly affect extensive livestock farming. Considering the current scenario, alternative approaches for parasite control are needed. This review study presents different Mediterranean tannin-rich plants with anthelmintic effect, which can be used as fodder or voluntarily grazed by livestock as a strategy to reduce the use of antiparasitic drugs. Internal parasites are one of the main causes of health threats in livestock production, especially in extensive livestock farming. Despite the environmental toxic effects (loss of dung beetles, biodiversity, and other issues) and resistance phenomenon derived from their prolonged use, anti-parasitic chemical pharmaceuticals are frequently used, even in organic farming. Such a situation within the context of climate change requires urgent exploration of alternative compounds to solve these problems and apparent conflicts between organic farming objectives regarding the environment, public health, and animal health. This review is focused on some plants (Artemisia spp., Cichorium intybus L., Ericaceae family, Hedysarum coronarium L., Lotus spp., Onobrychis viciifolia Scop.) that are well known for their antiparasitic effect, are voluntarily grazed and ingested, and can be spontaneously found or cultivated in southern Europe and other regions with a Mediterranean climate. The differences found between effectiveness, parasite species affected, in vitro/in vivo experiments, and active compounds are explored. A total of 87 papers where antiparasitic activity of those plants have been studied are included in this review; 75% studied the effect on ruminant parasites, where gastrointestinal nematodes were the parasite group most studied (70%), and these included natural (31%) and experimental (37%) infections. [ABSTRACT FROM AUTHOR]

We have previously demonstrated that the activation of rat parathyroid calcium-sensing receptor (CaSR) upregulates VDR expression in vivo (Garfia B, Canadillas S, Luque F, Siendones E, Quesada M, Almaden Y, Aguilera-Tejero E, Rodriguez M. J Am Soc Nephrol 13: 2945-2952, 2002; Rodriguez ME, Almaden Y, Canadillas S, Canalejo A, Siendones E, Lopez I, Aguilera-Tejero E, Martin D, Rodriguez M. Am J Physiol Renal Phvsiol 292: F1390-F1395, 2007). The present study was designed to characterize the signaling system that mediates the stimulation of parathyroid VDR gene expression by extracellular calcium. Experiments were performed in vitro by the incubation of rat parathyroid glands and in vivo with normal and uremic (Nx) rats receiving injections of Ca[Cl.sub.2] or EDTA to obtain hypercalcemic or hypocalcemic clamps. A high calcium concentration increased VDR expression. The addition of arachidonic acid (AA) to the low-calcium medium produced an increase in VDR mRNA of the same magnitude as that observed with high calcium. The addition of ionophore m the low-calcium medium also increased VDR mRNA expression. High calcium or the addition of AA to the low-calcium medium induced the activation (phosphorylation) of ERK1/2-MAPK. The specific inhibition of the ERK1/2-MAPK activity prevented the stimulation of VDR expression by high calcium or AA. These results suggest that AA regulates parathyroid VDR gene expression through the activation of the ERKI/ 2-MAPK. CaSR activation induced the activation of transcription factor Sp1, but not of NF-[kappa]B p50 or p65 or activator protein-1. The addition of AA to the low-calcium medium increased specific DNA-binding activity of Sp1 to almost the same level as high calcium, which was prevented by the inhibition of ERK1/2. Furthermore, mithramycin A (a Sp1 inhibitor) prevented the upregulation of VDR mRNA by high calcium. Finally, both sham and Nx hypercalcemic rats showed similar increased levels of VDR mRNA compared with sham and Nx hypocalcemic rats. Our results demonstrate that extracellular calcium stimulates VDR expression in parathyroid glands through the elevation of the cytosolic calcium level and the stimulation of the [PLA.sub.2]-AA-dependent ERK1/2-pathway. Furthermore, the transcription factor Spl mediates this effect. parathyroid glands; transcription factor; arachidonic acid; CaSR; PTH doi: 10.1152/ajprenal.00529.2009.

The immunomodulatory capacity of F. hepatica antigens is probably one of the main reasons for the development of a driven non-protective Th2 immune response. In this study, we analysed the cellular response of hepatic lymph node cells and CD4+ T cells in terms of proliferative response, efficiency of antigen presentation and cytokine production, to F. hepatica-derived molecules, at early and late stages of the infection. Thirty-one sheep were allocated into five groups and were slaughtered at 16 dpi and 23 wpi. In order to analyse antigen-specific response, the following F. hepatica recombinant molecules were used: rFhCL1, rFhCL2, rFhCL3, rFhCB1, rFhCB2, rFhCB3, rFhStf-1, rFhStf-2, rFhStf-3 and rFhKT1. A cell proliferation assay using hepatic lymph node cells and an antigen presentation cell assay using CD4+ T cells were performed. At 16 dpi, all molecules but rFhStf-2 and rFhKT1 elicited a significant cell proliferative response on hepatic lymph node cells of infected animals. At both early and late stage of the infection, antigen presentation of rFhCB3 and rFhCL2 resulted in higher stimulation index of CD4+ T cells which was IL-2 mediated, although no statistically significant when compared to uninfected animals. Significant cytokine production (IL-4, IL-10 and IFN-γ) was conditioned by the antigen-specific cell stimulation. No CD4+ T cell exhaustion was detected in infected sheep at the chronic stage of the infection. This study addressed antigen-specific response to F. hepatica-derived molecules that are involved in key aspects of the parasite survival within the host. [ABSTRACT FROM AUTHOR]

Purpose: To compare the induced corneal stromal bed roughness measured with atomic force microscopy (AFM) after LASIK flap creation with the IntraLase 60 kHz and the VisuMax femtosecond laser platforms. Methods: Three freshly enucleated porcine eyes were operated with each femtosecond laser in this experimental study. Standard LASIK treatment parameters were used for the experiment. After LASIK flap creation, the corneal stromal roughness was assessed using a JPK NanoWizard II® AFM in contact mode immersed in liquid. Olympus OMCL-RC800PSA commercial silicon nitride cantilever tips were used. Surface measurements were made in 10 regions of the central cornea of each sample measuring 20 x 20 microns, at 512 x 512 point resolution. Roughness was measured using the root-mean-square (RMS) value within the given regions. Results: Measurements from 30 regions of the 3 eyes (10 measurements per eye) in the Intralase (FS1) group, and 30 regions of the 3 eyes (10 measurements per eye) in the VisuMax (FS2) group were analyzed. There was a statistically significant difference in mean ± standard deviation RMS values between the FS1 and the FS2 groups (360 ± 120 versus 230 ± 100 nm respectively; P< 0.00001). Conclusion: This AFM study indicates that the surface of the stromal bed after LASIK flap creation is smoother in the FS2 group than the FS1 group. [ABSTRACT FROM AUTHOR]

Neuro Lyme disease is caused by several bacteriae of the Borreliaceae family, such as Borrelia Miyamotoi. In late stages of illness, patients with Lyme disease may develop chronic neurologic symptoms such as cognitive disturbances or small fiber peripheral neuropathy. Confocal microscopy is a non-invasive method designed to evaluate the human cornea in vivo. Thus, all the corneal layers, including the cells and the sub-basal nerve plexus, can be easily visualized and analyzed. This is the first report of the morphology of small-fiber peripheral neuropathy analyzed by confocal microscopy in a patient diagnosed of neuro Lyme disease. The decrease in the number of unmyelinated sub-basal nerve fibers with abundant presence of dendritic cells (DC) in comparison with healthy corneas strongly supports the diagnosis of small fiber peripheral neuropathy in a case of neuroborreliosis disease. [ABSTRACT FROM AUTHOR]

Background: Liver fluke infection of livestock causes economic losses of over US$ 3 billion worldwide per annum. The disease is increasing in livestock worldwide and is a re-emerging human disease. There are currently no commercial vaccines, and only one drug with significant efficacy against adult worms and juveniles. A liver fluke vaccine is deemed essential as short-lived chemotherapy, which is prone to resistance, is an unsustainable option in both developed and developing countries. Protein superfamilies have provided a number of leading liver fluke vaccine candidates. A new form of glutathione transferase (GST) family, Sigma class GST, closely related to a leading Schistosome vaccine candidate (Sm28), has previously been revealed by proteomics in the liver fluke but not functionally characterised. Methodology/Principal Findings: In this manuscript we show that a purified recombinant form of the F. hepatica Sigma class GST possesses prostaglandin synthase activity and influences activity of host immune cells. Immunocytochemistry and western blotting have shown the protein is present near the surface of the fluke and expressed in eggs and newly excysted juveniles, and present in the excretory/secretory fraction of adults. We have assessed the potential to use F. hepatica Sigma class GST as a vaccine in a goat-based vaccine trial. No significant reduction of worm burden was found but we show significant reduction in the pathology normally associated with liver fluke infection. Conclusions/Significance: We have shown that F. hepatica Sigma class GST has likely multi-functional roles in the host-parasite interaction from general detoxification and bile acid sequestration to PGD synthase activity. Author Summary: Combating neglected parasitic diseases is of paramount importance to improve the health of human populations and/or their domestic animals. Uncovering key roles in host-parasite interactions may support the vaccine potential portfolio of a parasite protein. Fasciola hepatica causes global disease in humans and their livestock but no commercial vaccines are available. Members of the Sigma class glutathione transferase (GST) family have long been highlighted as vaccine candidates towards parasitic flatworms. To this end, a Sigma class GST is currently undergoing phase II clinical trials to protect against infection from the schistosomes. In this study we characterise the protein from F. hepatica following four work pathways that 1) confirm its designation as a Sigma class GST using substrate profiling, 2) assess prostaglandin synthase activity and its effect on host immune cells, 3) localise the Sigma GST within adult fluke and between ontogenic stages and 4) measure its potential as a vaccine candidate. The work presented here shows F. hepatica Sigma class GST to have key host-parasite roles and we suggest, warrants further investigation for inclusion into vaccine formulations. [ABSTRACT FROM AUTHOR]

We have previously demonstrated that the activation of rat parathyroid calcium-sensing receptor (CaSR) upregulates VDR expression in vivo (Garfia B. Cañadillas S, Luque F, Siendones E, Quesada M, Almadén Y, Aguilera-Tejero E, Rodríguez M. J Am Soc Nephrol 13:2945-2952, 2002: Rodriguez ME, Almaden Y, Cañadillas S, Canalejo A, Siendones E, Lopez I, Aguilera-Tejero E, Martin D, Rodriguez M. Am J Physiol Renal Physiol 292: F1390-F1395, 2007). The present study was designed to characterize the signaling system that mediates the stimulation of parathyroid VDR gene expression by extracellular calcium. Experiments were performed in vitro by the incubation or rat parathyroid glands and in vivo with normal and uremic (Nx) rats receiving injections of CaCl2 or EDTA to obtain hypercalcemic or hypocalcemic clamps. A high calcium concentration increased VDR expression. The addition of arachidonic acid (AA) to the low-calcium medium produced an increase in VDR mRNA of the same magnitude as that observed with high calcium. The addition of ionophore to the low-tritium medium also increased VDR mRNA expression. High calcium or the addition of AA to the low-calcium medium induced the activation (phosphorylation) of ERK1/2-MAPK. The specific inhibition of the ERK1/2-MAPK activity prevented the stimulation of VDR expression by high calcium or AA. These results suggest that AA regulates parathyroid VDR gene expression through the activation of the ERK1/2-MAPK. CaSR activation induced the activation of transcription factor Sp1, but not of NF-κB p50 or p65 or activator protein-1. The addition of AA to the low-calcium medium increased specific DNA-binding activity of Sp1 to almost the same level as high calcium, which was prevented by the inhibition of ERK1/2. Furthermore, mithramycin A (a Sp1 inhibitor) prevented the upregulation of VDR mRNA by high calcium. Finally, both sham and Nx hypercalcemic rats showed similar increased levels of VDR mRNA compared with sham and Nx hypocalcemic rats. Our results demonstrate that extracellular calcium stimulates VDR expression in parathyroid glands through the elevation of the cytosolic calcium level and the stimulation of the PLA2-AA-dependent ERK1/2 pathway. Furthermore, the transcription factor Sp1 mediates this effect. [ABSTRACT FROM AUTHOR]

Simple Summary: Fasciolosis is a parasitic disease of livestock causing important economic losses worldwide and it is also a zoonosis. Current therapy relies on the use of anthelmintic drugs, which is no longer sustainable due to the increase of anthelmintic resistance and the risk of drug residues in food. A deep understanding of the host-parasite interaction is required to develop protective vaccines for the control of fasciolosis. The aim of the present study is to evaluate the hepatic lesions in sheep vaccinated with a partly protective vaccine for F. hepatica, a non-protective vaccine and an infected control group. The protective vaccine showed less severe hepatic lesions than the infected control group. In addition, in the protective vaccine group dead flukes surrounded by a severe granulomatous inflammation were observed, which taken together with the lower fluke burden, suggests that the host response induced by the partially protective vaccine may have been involved in the death of adult flukes of F. hepatica. This is the first study reporting the presence of degenerated flukes associated to a severe granulomatous inflammation in bile ducts in a vaccine trial, a finding that would be useful for improving vaccine efficacy in future trials. Fasciolosis is an important economic disease of livestock. There is a global interest in the development of protective vaccines since current anthelmintic therapy is no longer sustainable. A better knowledge of the host-parasite interaction is needed for the design of effective vaccines. The present study evaluates the microscopical hepatic lesions in sheep immunized with a partially protective vaccine (VAC1), a non-protective vaccine (VAC2), and an infected control group (IC). The nature of granulomatous inflammation associated with degeneration of adult flukes found in the VAC1 group was characterized by immunohistochemistry. Hepatic lesions (fibrous perihepatitis, chronic tracts, bile duct hyperplasia, infiltration of eosinophils and lymphocytes and plasma cells) were significantly less severe in the VAC1 group than in the IC group. Dead adult flukes within bile ducts were observed only in the VAC1 group and were surrounded by a severe granulomatous inflammation composed by macrophages and multinucleate giant cells with a high expression of lysozyme, CD163 and S100 markers, and a low expression of CD68. Numerous CD3+ T lymphocytes and scarce infiltrate of FoxP3+ Treg and CD208+ dendritic cells were present. This is the first report describing degenerated flukes associated to a severe granulomatous inflammation in bile ducts in a F. hepatica vaccine trial. [ABSTRACT FROM AUTHOR]

This case report describes a case of multiple follicular cysts in a 4-year-old Spanish purebred stallion. The lesions ranged in size from 0.5 to 3 cm in diameter, and were firm, well circumscribed and nonpruritic. They developed over a 2-year period with a generalized distribution affecting all body regions. Five nodules were removed and histopathologically corresponded to simple epidermal cysts (infundibular and isthmus-catagen) with squamous epithelium and a keratin filled cavity. Lesions were not evident at birth but their number, early age of detection, slow growth and lack of previous trauma suggested that they were congenital. To the authors’ knowledge, this condition has not previously been reported either in young horses or in Spanish purebred horses. [ABSTRACT FROM AUTHOR]

Background: The peritoneal cell populations (PCP) are thought to play a crucial role during the early immune response in Fasciola hepatica infection while newly excysted juveniles (NEJ) are migrating in the peritoneal cavity (PC) towards the liver. In this study, we aimed to determine the immunophenotypes of the PCP and to analyse the dynamics of the recruitment of the PCP during the early and late stage of the infection in sheep infected with F. hepatica. Methods: Thirty-seven sheep were divided into three groups: Group 1 (n = 20) and 2 (n = 10) were challenged with F. hepatica, Group 3 (n = 7) was not infected and remained as uninfected control (UC). After the slaughtering, peritoneal lavages were carried out to isolate peritoneal cell populations at 1, 3, 9 and 18 days post-infection (dpi) for Group 1 and at 14 weeks post-infection (wpi) for Group 2 and 3. Flow cytometry was conducted to assess the dynamics of peritoneal cavity cell populations. Results: TCD4 cells showed a significant decrease at 1 and 18 dpi when compared to UC; no statistical differences were detected for TCD8 and WC1+γδ during the early stage of the infection with respect to the UC. CD14 cells exhibited a decreasing trend, with a significant decrease at 9 and 18 dpi when compared to the UC. The dynamics of MHCII and CD83 cells showed a similar increasing pattern from 3 to 18 dpi. During the chronic stage, both TCD4 and TCD8 cells showed no significant differences when compared to the UC, although a slight but statistically significant higher level of WC1+γδ cells was observed. A lower percentage of antigen-presenting cells (APCs) was detected with respect to the UC. Conclusions: The recruitment of the lymphocytes subsets did not show a significant increase during the course of the infection and only WC1+γδ cells displayed a significant increase at the chronic stage. For the CD14, a decreasing trend was observed during the early stage, which was statistically significant at the chronic stage of the infection. Peritoneal CD83 and MHCII cells developed an increasing trend during the early stage of infection, and showed a significant decrease at the late stage of the infection. [ABSTRACT FROM AUTHOR]

The expression of T regulatory cells (Foxp3), regulatory (interleukin [IL]-10 and transforming growth factor beta [TGF-β]) and proinflammatory (tumor necrosis factor alpha [TNF-α] and interleukin [IL]-1β) cytokines was quantified using real time polymerase chain reaction (qRT-PCR) in the liver of sheep during early stages of infection with Fasciola hepatica (1, 3, 9, and 18 days post-infection [dpi]). Portal fibrosis was also evaluated by Masson's trichrome stain as well as the number of Foxp3+ cells by immunohistochemistry. Animals were divided into three groups: (a) group 1 was immunized with recombinant cathepsin L1 from F. hepatica (FhCL1) in Montanide adjuvant and infected; (b) group 2 was uniquely infected with F. hepatica; and (c) group 3 was the control group, unimmunized and uninfected. An overexpression of regulatory cytokines of groups 1 and 2 was found in all time points tested in comparison with group 3, particularly at 18 dpi. A significant increase of the number of Foxp3+ lymphocytes in groups 1 and 2 was found at 9 and 18 dpi relative to group 3. A progressive increase in portal fibrosis was found in groups 1 and 2 in comparison with group 3. In this regard, group 1 showed smaller areas of fibrosis than group 2. There was a significant positive correlation between Foxp3 and IL-10 expression (by immunohistochemistry and qRT-PCR) just as between portal fibrosis and TGF-β gene expression. The expression of proinflammatory cytokines increased gradually during the experience. These findings suggest the induction of a regulatory phenotype by the parasite that would allow its survival at early stages of the disease when it is more vulnerable. [ABSTRACT FROM AUTHOR]

Abstract: Protection against Fasciola hepatica in goats immunized with Peroxiredoxin (Prx) was assessed. The experimental trial consisted of three groups of seven animals; group 1 were unimmunized and uninfected, group 2 were immunized with adjuvant only and group 3 were immunized with recombinant Prx in adjuvant (immunized and infected). Immunization with Prx in Quil A adjuvant, group 3, induced a reduction in fluke burden of 33.04% when compared to adjuvant control, group 2, although this difference was not significant. The hepatic gross and microscopical morphometric study revealed lower damage in the Prx-immunized compared to group 2 (p <0.05). Furthermore, immunohistochemical studies revealed that the Prx-immunized group exhibited reduced infiltration of CD4+, CD8+, IFN-γ+ and TCR+ (p <0.05); and CD2+ and IL-4+ (p <0.001) in hepatic lesions. Levels of anti-Prx serum IgG in group 3 showed a significant increase at the 4th week after challenge infection compared with group 2 (p <0.0001). This is the first report of ruminant immunization with recombinant Prx of F. hepatica. The study shows that this vaccine significantly reduces hepatic damage and encourages further studies to improve the vaccine efficacy. [Copyright &y& Elsevier]

Sarcopenic obesity (SO) represents a major public health concern. Physical activity has been recommended to minimize functional decline in the elderly and it may also be relevant to SO management. The purpose of this systematic review of randomized controlled trials (RCTs) was to investigate the effects of different exercise modalities, alone or combined with nutritional supplementation, on body composition, muscle strength and physical function in healthy community-dwelling older adults with SO. A literature search was performed using the PubMed, SCOPUS, CINAHL and Cochrane Plus databases. The main inclusion criteria were that the papers were English-language reports of RCTs involving healthy community-dwelling adults aged ≥60 years with SO. The initial search identified 2073 publications from the 4 databases and 72 additional records; 42 full-text records were assessed for eligibility and 8 articles were finally included. The search was conducted from December 1, 2017 to January 8, 2018. The types of exercises were resistance and aerobic training, either alone or combined, and whole-body electromyostimulation. Protein supplementation was included in three studies. The diversity of the methodologies employed and of the results observed does not allow us to reach a clear conclusion. Whereas five of the studies reported improvements in obesity, results were contradictory concerning muscle mass. Increases in muscle strength appeared especially with resistance training and do not seem to be linked to protein supplementation. On the other hand, improvements in physical function were reported in programs combining aerobic and resistance training with nutritional supplementation. We believe that it is of the utmost importance that a certain degree of homogeneity is kept concerning the methods and criteria used in the diagnosis of SO, so that the effects of specific physical exercise programs, whether alone or combined with nutritional supplements, can be assessed with precision. [ABSTRACT FROM AUTHOR]

Fasciola hepatica is distributed worldwide, causing substantial economic losses in the animal husbandry industry. Human fasciolosis is an emerging zoonosis in Andean America, Asia, and Africa. The control of the disease, both in humans and animals, is based on using anthelmintic drugs, which has resulted in increased resistance to the most effective anthelmintics, such as triclabendazole, in many countries. This, together with the concerns about drug residues in food and the environment, has increased the interest in preventive measures such as a vaccine to help control the disease in endemic areas. Despite important efforts over the past two decades and the work carried out with numerous vaccine candidates, none of them has demonstrated consistent and reproducible protection in target species. This is at least in part due to the high immunomodulation capacity of the parasite, making ineffective the host response in susceptible species such as ruminants. It is widely accepted that a deeper knowledge of the host-parasite interactions is needed for a more rational design of vaccine candidates. In recent years, the use of emerging technologies has notably increased the amount of data about these interactions. In the present study, current knowledge of host-parasite interactions and their implication in Fasciola hepatica vaccine development is reviewed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Flores-Velázquez, Ruiz-Campillo, Herrera-Torres, Martínez-Moreno, Martínez-Moreno, Zafra, Buffoni, Rufino-Moya, Molina-Hernández and Pérez.)

The immunomodulatory capacity of F. hepatica antigens is probably one of the main reasons for the development of a driven non-protective Th2 immune response. In this study, we analysed the cellular response of hepatic lymph node cells and CD4 + T cells in terms of proliferative response, efficiency of antigen presentation and cytokine production, to F. hepatica-derived molecules, at early and late stages of the infection. Thirty-one sheep were allocated into five groups and were slaughtered at 16 dpi and 23 wpi. In order to analyse antigen-specific response, the following F. hepatica recombinant molecules were used: rFhCL1, rFhCL2, rFhCL3, rFhCB1, rFhCB2, rFhCB3, rFhStf-1, rFhStf-2, rFhStf-3 and rFhKT1. A cell proliferation assay using hepatic lymph node cells and an antigen presentation cell assay using CD4 + T cells were performed. At 16 dpi, all molecules but rFhStf-2 and rFhKT1 elicited a significant cell proliferative response on hepatic lymph node cells of infected animals. At both early and late stage of the infection, antigen presentation of rFhCB3 and rFhCL2 resulted in higher stimulation index of CD4 + T cells which was IL-2 mediated, although no statistically significant when compared to uninfected animals. Significant cytokine production (IL-4, IL-10 and IFN-γ) was conditioned by the antigen-specific cell stimulation. No CD4 + T cell exhaustion was detected in infected sheep at the chronic stage of the infection. This study addressed antigen-specific response to F. hepatica-derived molecules that are involved in key aspects of the parasite survival within the host.

Protection against Fasciola hepatica in goats immunized with a synthetic recombinant antigen from Schistosoma mansoni fatty acid-binding protein 14 (rSm14) was investigated by assessing worm burdens, serum levels of hepatic enzymes, faecal egg count and hepatic damage, which was evaluated using gross and microscopic morphometric observation. The nature of the local immune response was assessed by examining the distribution of CD2+, CD4+, CD8+ and γ´+ T lymphocytes along with IgG+, IL-4+ and IFN-γ+ cells in the liver and hepatic lymph nodes (HLN). The goats used consisted of group 1 (unimmunized and uninfected), group 2 [infected control - immunized with Quillaia A (Quil A)] and group 3 (immunized with rSm14 in Quil A and infected), each containing seven animals. Immunization with rSm14 in Quil A adjuvant induced a reduction in gross hepatic lesions of 56.6% (p < 0.001) and reduced hepatic and HLN infiltration of CD2+, CD4+, CD8+ and γ´+ T lymphocytes as well as IL-4+ and IFN-γ+ cells (p < 0.05). This is the first report of caprine immunization against F. hepatica using a complete rSm14 molecule derived from S. mansoni. Immunization reduced hepatic damage and local inflammatory infiltration into the liver and HLN. However, considering that Quil A is not the preferential/first choice adjuvant for Sm14 immunization, further studies will be undertaken using the monophosphoryl lipid A-based family of adjuvants during clinical trials to facilitate anti-Fasciolavaccine development.