Local immune response of Canarian Majorera goats infected with Teladorsagia circumcincta

Background Due to increased anthelmintic resistance, alternative methods to drugs are necessary to control gastrointestinal nematodes (GINs). Some of the most promising alternatives are based on the immune response of the host, such as the selection of genetically resistant breeds or the use of vaccines against these parasites. Given the limited information available on the immune response against GINs in goats, this study investigated the local immune response of goat kids of an indigenous Canary Islands breed (Majorera breed) experimentally infected with Teladorsagia circumcincta, one of the most pathogenic and prevalent GIN species. Methods For this purpose, the relationship between different parasitological (number of mature and immature worms, worm length, and number of intrauterine eggs) and immunological parameters at the local level (related to both the humoral and cellular immune response) was analyzed at early (1 week post-infection [wpi]) and late (8 wpi) stages of infection. Results Primary infection of goat kids with T. circumcincta infective larvae (L3) generated a complex immune response that could be defined as Th2 type, characterized by increased infiltration in abomasal tissues of several effector cells as well as a progressive presence of specific antibodies against parasitic antigens in the gastric mucus. Cellular responses were evidenced from 1 wpi onward, showing an increase in antigen-presenting cells and various lymphocyte subsets in the gastric mucosa. Conclusions The complexity of the host response was evidenced by statistically significant changes in the number of all these subpopulations (MHCII+, CD4+, CD8+, γδ+, CD45R+, IgA+, and IgG+), as well as in the evolution of the relative cytokine gene expression. From a functional point of view, negative associations were observed between the number of most of the immune cells (CD4, IgA, IgG, and CD45R cells) and parameters that could be related to the fecundity of worms, a phenomenon that was especially evident when the number of IgG and CD45R cells or the specific IgA levels of the gastric mucus were compared with parasitological parameters such as the female worm length or fecal egg counts at 8 wpi. Graphical Abstract

FAPI PET/CT in the Diagnosis of Abdominal and Pelvic Tumors

Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDG) is currently a standard imaging examination used in clinical practice, and plays an essential role in preoperative systemic evaluation and tumor staging in patients with tumors. However, 18F-FDG PET/CT has certain limitations in imaging of some tumors, like gastric mucus adenocarcinoma, highly differentiated hepatocellular carcinoma, renal cell carcinoma, and peritoneal metastasis. Therefore, to search for new tumor diagnosis methods has always been an important topic in radiographic imaging research. Fibroblast activation protein (FAP) is highly expressed in many epithelial carcinomas, and various isotope-labelled fibroblast activation protein inhibitors (FAPI) show lower uptake in the brain and abdominal tissues than in tumor, thus achieving high image contrast and good tumor delineation. In addition to primary tumors, FAPI PET/CT is better than FDG PET/CT for detecting lymph nodes and metastases. Additionally, the highly selective tumor uptake of FAPI may open up new application areas for the non-invasive characterization, staging of tumors, as well as monitoring tumor treatment efficacy. This review focuses on the recent research progress of FAPI PET/CT in the application to abdominal and pelvic tumors, with the aim of providing new insights for diagnostic strategies for tumor patients, especially those with metastases.

Potential and beneficial effects of Cinnamomum cassia on gastritis and safety: Literature review and analysis of standard extract

The prevalence of gastritis in South Korea is rapidly increasing owing to the prevalence of Helicobacter pylori infection and fast eating habit. The usual treatment for acute gastritis following a long intake of non-steroidal anti-inflammatory drugs (NSAIDs) or alcohol is to stop the causal factors. Metronidazole and lansoprazole are recommended for the treatment of H. pylori infection gastritis. Omeprazole a proton pump inhibitor, is used to decrease gastric acid production. However, owing to the side effects and refractoriness of the drug, a safe and efficient treatment is required. Plant-derived phytochemicals have emerged as novel agents against chronic disorders. In this study, firstly, to explore the potential of pharmacological activities, including efficacy and mechanisms of Cinnamomum cassia against gastritis, a literature review was performed based on 20 studies out of a total of 749 records obtained using a search strategy. From the literature review, the therapeutic targets of C. cassia extract and cinnamaldehyde, a compound of C. cassia, were found to be related with NFκB activity, and their signaling pathway were verified by experiments. C. cassia extract plays a role in protection of gastric ulcers induced in four ways (immersion stress-induced, ethanol-induced, hydrochloric acid-induced, or NSAIDs-induced ulcer). None of the clinical studies on C. cassia extracts or compounds met our criteria. When the standardized extract of C. cassia (ECC) was orally administered repeatedly to Beagle Dog for 4 weeks, no toxicologically harmful changes were observed. Therefore, under the test condition, the no observed adverse effect level (NOAEL) of ECC was judged to be 1000 mg/kg/day for both sexes, and no toxic target organ was observed. Administration of ECC in the Sprague–Dawley rat model of acute gastric injury caused by indomethacin administration significantly increased gastric mucus volume. Administration of ECC in the acute gastric injury model caused by indomethacin administration is considered effective in improving gastric injury. However, research and efforts to develop a reliable ‘standardization of natural drugs’ by establishing the best quality evaluation system are limited. Despite the pharmacological potential of ECC, further well-designed experimental studies such as in vitro, in vivo, and clinical trials are required to validate these findings and the underlying mechanisms of ECC.

61 Oral Dosing Loline Alkaloid and Its Effects Against Mixed Infection of L4 Teladorsagia Circumcincta, and Trichostrongylus Colubriformis, and Adult Haemonchus Contortus

Loline, an alkaloid produced by Epichloë endophytes in pastoral grass species, is considered non-toxic with suggested antimicrobial and anthelmintic properties. In vivo metabolism of loline suggests ability to reach the abomasum or intestine, and anthelmintic benefit is indicated in vitro when parasites are in either a developmental stage close to the gastric mucus layers or adult stage consuming blood. Therefore, the objective of this project was to investigate the validation of using a loline seed extract as a natural anthelmintic in parasitized lambs. Sixteen Coopworth lambs were individually penned, offered ad-libitum lucerne pellets and water and randomly assigned to 3 treatment groups; CON; no treatment, or treatment with a Festuca pratensis seed extract with (LOL) or without loline (NIL). Lambs were orally infected with 20,0000 L3 Haemonchus contortus on day 0, and 10,000 L3 Teladorsagia circumcincta, and Trichostrongylus colubriformis on day 14. Parasites then matured to determine lolines efficacy on blood feeding adult Haemonchus contortus and L4 mucosal browsers Teladorsagia circumcincta, and Trichostrongylus colubriformis. Loline was orally dosed at 52.5 mg/kg LW starting on day 13, and every other day until slaughter for worm enumeration on day 28. Feed intake and refusals were recorded daily, and fecal samples were taken prior to infection, on loline dose days and at slaughter. Worm and fecal egg counts were transformed to log10 and all data were analyzed in Genstat (18th edition). Significance was declared at P < 0.05. Worm burdens of T. circumcincta (P = 0.96), T. colubriformis (P = 0.43), and H. contortus (P = 0.15) were not different between treatments. No treatment difference (P = 0.39) was observed in fecal egg counts, weight gain (P = 0.51), or feed intake (P = 0.18). Average growth efficiency (kg LWG/ kg DM intake) was 0.18 in CON which was less (P = 0.01) than LOL (0.24) or NIL (0.23). In conclusion, limited evidence supported an in vivo anti-parasitic effect of loline.

Trefoil Factor Family (TFF) Peptides

Trefoil factor family (TFF) peptides mainly consist of characteristic TFF domains, which contain about 40 amino acid residues, including 6 conserved cysteine residues. TFF peptides possess a single (mammalian TFF1 and TFF3), two (mammalian TFF2, Xenopus laevis xP2) or four TFF domains (X. laevis xP4). They exhibit lectin activities and are characteristic exocrine products of the mucous epithelia. Here, they play different roles for mucosal protection and the innate immune defense: TFF1 is a gastric tumor suppressor; TFF2 builds a lectin complex with the mucin MUC6, physically stabilizing the inner gastric mucus layer; and TFF3 forms a disulfide-linked heterodimer with IgG Fc binding protein (FCGBP), probably preventing the infiltration of microorganisms. Minor amounts of TFF peptides are endocrine products of the immune and nervous systems. Pathologically, TFF peptides are linked to inflammation. There are increasing indications that TFF peptides can antagonize cytokine receptors, such as receptors for IL-1β, IL-6, and TNFα (thereby acting as anti-inflammatory peptides). TFF peptides can probably also activate a variety of receptors, such as CXCR4. The TFF domain is a unique shuffled module which is also present in a number of mosaic proteins, such as zona pellucida proteins, sugar degrading enzymes and frog skin mucins. Here, their function seems to be defined by a lectin activity, which might even allow a role in fertilization.

Local Immune Response of Canarian Majorera Goats Primary Infected With Teladorsagia Circumcincta

Due to increased anthelmintic resistance, alternative methods to drugs are necessary to control gastrointestinal nematodes (GIN). Some of the most promising alternatives for their sustainability are based on the immune response of the host, such as the selection of genetically resistant breeds or the use of vaccines against these parasites. Given the limited information available on the immune response against GIN in goats, this study was carried out on the local immune response of goat kids of a Canary Islands indigenous breed (Majorera breed) experimentally infected with Teladorsagia circumcincta, one of the most pathogenic and prevalent GIN species. For this purpose, the relationship between different parasitological and immunological parameters at local level (both related to the humoral and cellular immune responses) have been analyzed at early (1 week post-infection –wpi-) and late (8 wpi) stages of infection.Primoinfection of goat kids with T. circumcincta L3 generates a complex immune response that could be defined as Th2 type, characterized by an increase of infiltration in abomasal tissues of several effector cells as well as a progressive presence of specific antibodies against parasitic antigens in the gastric mucus. These cellular responses could be evidenced from 1 wpi onward, showing an increase in the gastric mucosa of antigen presenting cells and various lymphocyte subsets. The complexity of the responses developed is evidenced by the statistically significant changes in numbers of all these subpopulations, as well as in the evolution of the relative cytokine gene expression. From a functional point of view, negative associations were observed between the number of most of these cells (CD4, IgA, IgG, and CD45R cells) and parameters that could be related to the fecundity of worms, a phenomenon that was especially evident when the number of IgG or CD45R cells or the specific IgA levels of the mucus were compared with parasitological parameters such as the lenght of female worms or faecal egg counts at 8wpi.

Trefoil Factor Family (TFF) Peptides and their Different Roles in the Mucosal Innate Immune Defense and More: An Update

: Mucous epithelia are protected by complex mucus barrier layers, which are part of the innate immune defense. Trefoil factor family peptides TFF1, TFF2, and TFF3 have lectin activities and are predominantly co-secreted together with mucins from these epithelia. TFF1 and TFF2 are mainly expressed in the gastric mucosa; whereas TFF3 is rather widely secreted from most mucous epithelia and their glands. TFF1 and TFF3 consist of a single TFF domain and an additional free 7th cysteine residue; whereas TFF2 contains two TFF domains. Systematic analyses of the molecular forms of TFFs gave new insights into their diverse molecular functions. TFF1 mainly exists as a monomer with an unusual free thiol group and only minor amounts form a disulfide linked homodimer as well as heterodimers with gastrokine-2 and IgG-Fc-binding protein (FCGBP). TFF3 mainly forms a heterodimer with FCGBP in vivo, but binds also Deleted in Malignant Brain Tumors/gp340 (DMBT1gp340) in vitro. In contrast, TFF2 binds as a lectin to a conserved O-linked carbohydrate moiety of the mucin MUC6. Both FCGBP and DMBT1gp340 are secreted from most mucous epithelia and their glands and are involved in mucosal innate immunity. Thus, a new picture emerged pointing to functions of TFF3-FCGBP (and TFF1-FCGBP) for mucosal innate immune defense, e.g. supporting the clearing of microorganisms. Such a function could be well be supported by DMBT1gp340. In contrast, the TFF2/MUC6 complex probably stabilizes physically the inner adherent gastric mucus layer. Furthermore, there are indications that TFF3-FCGBP might play also a role in blood vessels.

Efficacy of a chitosan-curcumin mixture in treating indomethacin-induced acute gastric ulcer in rats

Background: Curcumin is claimed as a potent protectant against gastric ulcer (GU) induced by strong necrotizing agents including NSAIDs through its antioxidant, anti-inflammatory and gastroprotective activities. However, it was found to exert opposite effects to either delay ulcer healing or exacerbate ulcer inflammation through some curative mechanisms differently modified by curcumin dosage. Its ability in inhibiting the expression of COX-2 may also delay the healing of NSAIDs-induced GU. Recently, a topical chitosan-curcumin solution has been found to be a safe and potential alternative agent in treating oral ulcer. Therefore, an oral chitosan-curcumin mixture was developed and determined for its efficacy in treating NSAIDs-induced GU in rat. Methods: A chitosan (150 mg)-curcumin (20 mg) mixture with optimal gastric pH was developed. Indomethacin (30 mg/kg) was given orally to the rat and test preparations were administered orally at 5 h later and then every 24 h for two consecutive days. The sum of all gastric ulcerated areas (mm2) for each stomach was used as ulcer index. Gastric pro-inflammatory mediators and cytoprotective factors were determined. Results: An oral administration of a chitosan-curcumin mixture exerted a superior efficacy than curcumin, chitosan or lansoprazole (a standard antiulcer agent) in healing indomethacin-induced GU. It was revealed that the mixture exhibited the highest anti-oxidant, anti-inflammatory and gastric mucus producing activities including the high potency in down-regulating pro-inflammatory COX-2 and iNOS expression but up-regulating cytoprotective COX-1, nNOS and eNOS expression. Conclusion: The present findings indicated the benefit of a chitosan-curcumin mixture as a potential alternative agent in treating NSAIDs-induced gastric ulcer.

Brassica oleracea Prevents HCl/Ethanol-Induced Gastric Damages in Mice

Brassica oleracea var. capitata L. (cabbage) is a popular vegetable with a wide range of pharmacological activities that help to promote human health. The present study investigated the beneficial effects of B. oleracea var. capitata L. extract (BOE) on HCl/ethanol (H/E)-induced gastric damages in mice. Pre-administration of BOE (25–100 mg/kg) for 7 consecutive days significantly decreased macroscopically visible lesion on the gastric mucosa induced by H/E. In addition, results from hematoxylin and eosin-stained gastric tissue showed that BOE inhibited invaded percentage of lesion and prevented the reduction in mucosal thickness in peri-ulcerative region. BOE significantly alleviated the H/E-mediated decreases in Alcian blue binding, total hexose, sialic acid, and collagen in the gastric tissue, suggesting BOE attenuates the gastric damage via preserving the integrity of gastric mucus. Moreover, BOE significantly decreased histamine level in the plasma and reduced mRNA levels associated with secreting gastric acid. Furthermore, BOE inhibited myeloperoxidase activity and suppressed nuclear factor-κB mRNA and its dependent inflammatory genes expression induced by H/E. BOE also strengthened antioxidant enzyme activity, with a mitigating H/E-mediated increase in malondialdehyde level of the gastric tissue. Thus, these results suggest that BOE has the potential to protect the gastric tissue via inhibiting gastric acid secretion, inflammation, and oxidative stress.