Underneath the Gut-Brain Axis in IBD-Evidence of the Non-Obvious.

The gut-brain axis (GBA) plays a pivotal role in human health and wellness by orchestrating complex bidirectional regulation and influencing numerous critical processes within the body. Over the past decade, research has increasingly focused on the GBA in the context of inflammatory bowel disease (IBD). Beyond its well-documented effects on the GBA-enteric nervous system and vagus nerve dysregulation, and gut microbiota misbalance-IBD also leads to impairments in the metabolic and cellular functions: metabolic dysregulation, mitochondrial dysfunction, cationic transport, and cytoskeleton dysregulation.

Anti-Opisthorchis felineus effects of artemisinin derivatives: An in vitro study.

Background: The drug of choice for the treatment of opisthorchiasis caused by trematodes Opisthorchis viverrini and O. felineus is praziquantel (PZQ), but there is a constant search for new anthelmintics, including those of plant origin. Positive results on the use of artemisinin derivatives against O.

Curcumin and Its Supramolecular Complex with Disodium Glycyrrhizinate as Potential Drugs for the Liver Fluke Infection Caused by .

Opisthorchiosis is a parasitic liver disease found in mammals that is widespread throughout the world and causes systemic inflammation. Praziquantel remains the drug of choice for the treatment of opisthorchiosis, despite its many adverse effects. An anthelmintic effect is attributed to the main curcuminoid of L.

Combination of common mtDNA variants results in mitochondrial dysfunction and a connective tissue dysregulation.

Mitochondrial dysfunction can be associated with a range of clinical manifestations. Here, we report a family with a complex phenotype including combinations of connective tissue, neurological, and metabolic symptoms that were passed on to all surviving children. Analysis of the maternally inherited mtDNA revealed a novel genotype encompassing the haplogroup J - defining mitochondrial DNA (mtDNA) m.

Prolonged liver fluke infection combined with alcoholization: An experimental mouse model.

Liver fluke infections disrupt the bile-excreting function of the human liver. Worldwide, excessive alcohol consumption also leads primarily to liver diseases. Our aim was to comprehensively assess the liver state in mice in parallel with the characterization of inflammation when the two adverse factors were combined.

Behavioral effects and inflammatory markers in the brain and periphery after repeated social defeat stress burdened by Opisthorchis felineus infection in mice.

The combination of 4-week repeated social defeat stress (RSDS) and Opisthorchis felineus infection was modeled in C57BL/6 mice. Various parameters were compared between three experimental groups of male mice (SS: mice subjected to RSDS, OF: mice infected with O. felineus, and OF + SS: mice subjected to both adverse factors) and behavior-tested and intact (INT) controls.

A tumorigenic cell line derived from a hamster cholangiocarcinoma associated with Opisthorchis felineus liver fluke infection.

Aims: The food-born trematode Opisthorchis felineus colonizes bile ducts of the liver of fish-eating mammals including humans. There is growing evidence that this liver fluke is a risk factor for cholangiocarcinoma (CCA). Cancer cell lines are necessary for drug screening and for identifying protein markers of CCA.

Effects of Three-time Administration of a Supramolecular Complex of Praziquantel with Disodium Glycyrrhizinate on Trematode Opisthorchis felineus in Hamsters.

Background: Praziquantel (PZQ) is the most commonly used anthelmintic drug for treating trematodiases. It was shown here that PZQ in complex with disodium glycyrrhizinate (PZQ-NaGA, in the 1:10 ratio) has higher bioavailability than PZQ alone. Our aim was to determine the effects of three-time administration of PZQ-NaGA in an experimental opisthorchiasis felinea model.

The pathogenic potential of the combined action of chronic Opisthorchis felineus infection and repeated social defeat stress in C57BL/6 mice.

Parasitic food-borne diseases and chronic social stress are frequent attributes of day-to-day human life. Therefore, our aim was to model the combined action of chronic Opisthorchis felineus infection and repeated social defeat stress in C57BL/6 mice. Histological examination of the liver revealed inflammation sites, pronounced periductal fibrosis, and cholangiofibrosis together with proliferation of bile ducts and hepatocyte dystrophy in the infected mice, especially in the stress-exposed ones.

Effect of Silicon Dioxide Nanoparticles on Syrian Hamsters Infected by Opisthorchis felineus: H MRS Study of the Brain.

In recent years, silicon dioxide nanoparticles have been widely used in medicine and the pharmaceutical industry, however, their effect on the brain has hardly been studied. We assessed the effects of long-term consumption of 5-nm amorphous silicon dioxide nanoparticles (SiO-NPs) by Syrian hamsters infected with the trematodes Opisthorchis felineus on the hippocampus and frontal cortex. Spectroscopic determination of brain neurometabolites, performed using a horizontal Magnetic Resonance Imaging system at 11.

From 2D to 3D: Promising Advances in Imaging Lung Structure.

The delicate structure of murine lungs poses many challenges for acquiring high-quality images that truly represent the living lung. Here, we describe several optimized procedures for obtaining and imaging murine lung tissue. Compared to traditional paraffin cross-section and optimal cutting temperature (OCT), agarose-inflated vibratome sections (aka precision-cut lung slices), combines comparable structural preservation with experimental flexibility.

Social defeat stress exacerbates the blood abnormalities in Opisthorchis felineus-infected mice.

A model of chronic opisthorchiasis combined with social stress is examined; this situation is more likely for humans and animals than a separate impact of the infectious factor. For this purpose, we evaluated the effects of Opisthorchis felineus ("OP" group) and 30-day social stress (confrontations between males, "SS" group) alone and in combination ("OP + SS" group) in inbred C57BL/6 male mice and compared these effects according to the parameters listed below. The animals exposed to neither factor formed the control group ("CON").

Mitochondrial DNA associations with East Asian metabolic syndrome.

Mitochondrial dysfunction has repeatedly been reported associated with type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS), as have mitochondrial DNA (mtDNA) tRNA and duplication mutations and mtDNA haplogroup lineages. We identified 19 Taiwanese T2DM and MS pedigrees from Taiwan, with putative matrilineal transmission, one of which harbored the pathogenic mtDNA tRNA nucleotide (nt) 3243A>G mutation on the N9a3 haplogroup background. We then recruited three independent Taiwanese cohorts, two from Taipei (N = 498, mean age 52 and N = 1002, mean age 44) and one from a non-urban environment (N = 501, mean age 57).

Dual MAPK Inhibition Is an Effective Therapeutic Strategy for a Subset of Class II BRAF Mutant Melanomas.

Purpose: Dual MAPK pathway inhibition (dMAPKi) with BRAF and MEK inhibitors improves survival in BRAF V600E/K mutant melanoma, but the efficacy of dMAPKi in non-V600 BRAF mutant tumors is poorly understood. We sought to characterize the responsiveness of class II (enhanced kinase activity, dimerization dependent) BRAF mutant melanoma to dMAPKi.

Experimental Design: Tumors from patients with BRAF wild-type (WT), V600E (class I), and L597S (class II) metastatic melanoma were used to generate patient-derived xenografts (PDX).

Clinical application of a cancer genomic profiling assay to guide precision medicine decisions.

Aim: Develop and apply a comprehensive and accurate next-generation sequencing based assay to help clinicians to match oncology patients to therapies.

Materials & Methods: The performance of the CANCERPLEX assay was assessed using DNA from well-characterized routine clinical formalin-fixed paraffin-embedded (FFPE) specimens and cell lines.

Results: The maximum sensitivity of the assay is 99.

Association Between Mitochondrial DNA Haplogroup Variation and Autism Spectrum Disorders.

Importance: Autism spectrum disorders (ASD) are characterized by impairments in social interaction, communication, and repetitive or restrictive behavior. Although multiple physiologic and biochemical studies have reported defects in mitochondrial oxidative phosphorylation in patients with ASD, the role of mitochondrial DNA (mtDNA) variation has remained relatively unexplored.

Objective: To assess what impact mitochondrial lineages encompassing ancient mtDNA functional polymorphisms, termed haplogroups, have on ASD risk.

Secretion of Thioredoxin Peroxidase Protein of Cat Liver Fluke Opisthorchis felineus during Modeling of Experimental Opisthorchiasis.

Mechanisms of thioredoxin peroxidase secretion by Opisthorchis felineus were studied in vivo and in vitro. Specific antibodies were obtained and used for western blotting and immunohistochemical detection in Syrian hamster model of opisthorchiasis. Secreted thioredoxin peroxidase protein was accumulated in the worm incubation medium under conditions of oxidative stress and in bile duct cells of hamsters with chronic opisthorchiasis.

Hemozoin is a product of heme detoxification in the gut of the most medically important species of the family Opisthorchiidae.

Many species of trematodes such as Schistosoma spp., Fasciola hepatica and Echinostoma trivolvis are blood-feeding parasites. Nevertheless, there is no consensus on the feeding habits of the family Opisthorchiidae (Opisthorchis felineus, Opisthorchis viverrini and Clonorchis sinensis).

Combined effects of social stress and liver fluke infection in a mouse model.

The effects of two influences, social stress and acute opisthorchiasis, were investigated in inbred C57BL/6J male mice. In the model of social stress, mice were repeatedly attacked and defeated by aggressive outbred ICR male mice and were in continuous sensory contact with an aggressive conspecific mouse in their home cage for 20 days. Acute opisthorchiasis was provoked by invasion of Opisthorchis felineus (50 larvae per animal) on the fourth day after the social stress was induced.

Effect of Opisthorchis felineus infection and dimethylnitrosamine administration on the induction of cholangiocarcinoma in Syrian hamsters.

The food-borne liver trematode is an emerging source of biliary tract diseases on the territory of the former Soviet Union and Eastern Europe. This parasite along with trematodes and belong to the triad of epidemiologically important liver flukes of the Opisthorchiidae family. It is known that and are the main risk factors of cholangiocarcinoma (CCA) in the endemic regions.

Peripheral Blood Mitochondrial DNA as a Biomarker of Cerebral Mitochondrial Dysfunction following Traumatic Brain Injury in a Porcine Model.

Background: Traumatic brain injury (TBI) has been shown to activate the peripheral innate immune system and systemic inflammatory response, possibly through the central release of damage associated molecular patterns (DAMPs). Our main purpose was to gain an initial understanding of the peripheral mitochondrial response following TBI, and how this response could be utilized to determine cerebral mitochondrial bioenergetics. We hypothesized that TBI would increase peripheral whole blood relative mtDNA copy number, and that these alterations would be associated with cerebral mitochondrial bioenergetics triggered by TBI.

[Role of opisthorchis felineus on induction of bile duct cancer].

Opisthorchis felineus (Trematoda) is widespread in the Russian Federation, especially in Siberia, and other countries of Europe. Infestation of endemic area population with O. felineus reaches 80%.

[Secretome of the adult liver fluke Opisthorchis felineus].

The opisthorchiasis caused by Opisthorchis felineus, the Siberian liver fluke remains a serious public health problem in Russia and Eastern Europe. Proteomic identification of the proteins in the excretory-secretory products (ESPs) released by O. felineus is an important key for the investigation of host-parasite interactions and understanding the mechanisms involved in parasite survival within the host.

Progressive increase in mtDNA 3243A>G heteroplasmy causes abrupt transcriptional reprogramming.

Variation in the intracellular percentage of normal and mutant mitochondrial DNAs (mtDNA) (heteroplasmy) can be associated with phenotypic heterogeneity in mtDNA diseases. Individuals that inherit the common disease-causing mtDNA tRNA(Leu(UUR)) 3243A>G mutation and harbor ∼10-30% 3243G mutant mtDNAs manifest diabetes and occasionally autism; individuals with ∼50-90% mutant mtDNAs manifest encephalomyopathies; and individuals with ∼90-100% mutant mtDNAs face perinatal lethality. To determine the basis of these abrupt phenotypic changes, we generated somatic cell cybrids harboring increasing levels of the 3243G mutant and analyzed the associated cellular phenotypes and nuclear DNA (nDNA) and mtDNA transcriptional profiles by RNA sequencing.

Mitochondrial DNA variant associated with Leber hereditary optic neuropathy and high-altitude Tibetans.

The distinction between mild pathogenic mtDNA mutations and population polymorphisms can be ambiguous because both are homoplasmic, alter conserved functions, and correlate with disease. One possible explanation for this ambiguity is that the same variant may have different consequences in different contexts. The NADH dehydrogenase subunit 1 (ND1) nucleotide 3394 T > C (Y30H) variant is such a case.