Potential Hepatic Lipid Markers Associated with Nonalcoholic Steatohepatitis and Fibrosis in Morbid Obesity Patients.

This study investigated differences in lipidomic profile features in nonalcoholic steatohepatitis (NASH) between mild and significant liver fibrosis cases among patients with morbid obesity. Wedge liver biopsy was performed during sleeve gastrectomy and significant liver fibrosis was defined as a fibrosis score ≥ 2. We selected patients with NASH with non/mild fibrosis (stage F0-F1; n = 30) and NASH with significant fibrosis (stage F2-F4; n = 30). The results of the liver tissue lipidomic analysis revealed that the fold changes of triglyceride (TG) (52:6); cholesterol ester (CE) (20:1); phosphatidylcholine (PC) (38:0) and (50:8); phosphatidic acid (PA) (40:4); phosphatidylinositol (PI) (49:4); phosphatidylglycerol (PG) (40:2); and sphingomyelin (SM) (35:0) and (37:0) were significantly lower in patients with NASH with F2-F4 than those with NASH with F0-F1 (p < 0.05). However, the fold changes of PC (42:4) were relatively higher in patients with NASH with stage 2-4 fibrosis (p < 0.05). Moreover, predictive models incorporating serum markers levels, ultrasonographic studies, and levels of specific lipid components [PC (42:4) and PG (40:2)] yielded the highest area under receiver operating curve (0.941), suggesting a potential correlation between NASH fibrosis stages and liver lipid accumulation among specific lipid species subclasses. This study demonstrated that the concentrations of particular lipid species in the liver correlate with NASH fibrosis stages and may indicate hepatic steatosis regression or progression in patients with morbid obesity.

Mitochondrial Factor C20orf7 Facilitates the EMT-Mediated Cancer Cell Migration and the Proliferation of Colon Cancer In Vitro and In Vivo.

Colon cancer is a major malignant neoplasm with a low survival rate for late-stage patients. Therefore, the investigation of molecules regulating colon cancer progression and the discovery of novel therapeutic targets is critical. Mitochondria play a vital role in maintaining the homeostasis of cells. Abnormal mitochondrial metabolism alterations and the induction of glycolysis can facilitate tumor growth; therefore, targeting mitochondrial molecules is suggested to be a promising strategy for cancer treatment. In this study, we investigated the role of this largely unknown mitochondrial factor, chromosome 20 open reading frame 7 (C20orf7), in colon cancer progression. Clustered regularly interspaced short palindromic repeats (CRISPR) technology was utilized for C20orf7 depletion, and functional assays were performed to examine the regulation of C20orf7 in colon cancer cells. We demonstrated that C20orf7 facilitates epithelial-mesenchymal transition (EMT)-mediated cell migration and promotes the proliferation of colon cancer. The anti-cancer drug 5-fluorouracil (5FU) was also applied, and C20orf7 was targeted with a combination of 5FU treatment, which could further enhance the anti-cancer effect in the colon cancer cell line and the xenograft mice model. In summary, this study demonstrated, for the first time, that C20orf7 plays a promotional role in cancer tumorigenesis and could be a promising therapeutic target in colon cancer treatment.

Validation of a focused echocardiographic training program in first opinion practice.

BACKGROUND: The EPIC study defines criteria, including echocardiographic assessments of left atrial to aortic ratio (LA: Ao) and left ventricular internal diameter in diastole normalized for body weight (LVIDdN), for dogs with preclinical myxomatous mitral valve disease (MMVD) likely to benefit from pimobendan therapy. Access to echocardiography by a cardiologist is not universally available. HYPOTHESIS/OBJECTIVES: Completion of a focused echocardiographic training program would result in accurate identification of dogs fulfilling the EPIC criteria by primary care veterinarians (PC). PARTICIPANTS: Six PCs with no previous echocardiographic experience. METHODS: Prospective diagnostic test accuracy study. After training, each PC evaluated ≤10 dogs that they believed to have preclinical MMVD. The evaluation was repeated by 1 of 3 cardiology diplomates, blinded to the PC's findings. Agreement between clinical assessments and echocardiographic measurements was assessed. RESULTS: Fifty-seven dogs were evaluated by PCs; 1 dog was withdrawn because of congestive heart failure. The median time between PC and cardiologist evaluation was 0 days (range, 0-8). One incorrect diagnosis of MMVD was made by a PC (this dog had dilated cardiomyopathy [DCM]); preclinical MMVD was confirmed by the cardiologist in 55 dogs. No difference in LA: Ao (P = .96; CV = 6.9%) was detected between PCs and cardiologists. LVIDdN (1.69 cm/kg0.294 (1.26-2.21) vs 1.73 cm/kg0.294 (1.32-2.73); P = .001; CV = 6.5%), was significantly lower when measured by PCs vs cardiologists. PCs and cardiologists agreed regarding assessment of EPIC criteria in 49/56 dogs (Alpha = .761, 95% confidence interval 0.697-0.922). CONCLUSIONS AND CLINICAL IMPORTANCE: The program effectively trained PCs to accurately assess EPIC criteria in dogs with preclinical MMVD.

Fish oil ameliorates neuropsychiatric behaviors and gut dysbiosis by elevating selected microbiota-derived metabolites and tissue tight junctions in rats under chronic sleep deprivation.

Neuropsychiatric behaviors caused by sleep deprivation (SD) are severe public health problems in modern society worldwide. This study investigated the effect of fish oil on neuropsychiatric behaviors, barrier injury, microbiota dysbiosis, and microbiota-derived metabolites in SD rats. The rats subjected to SD had significantly elevated blood levels of corticosteroid and lipopolysaccharides and exhibited anxiety-like behavior in the open field test, depression-like behavior in the forced swim test, and cognitive impairment in the Morris water maize test. We observed that the upregulation of proinflammatory cytokines in the SD rats resulted in colonic epithelial barrier injury including a decreased number of goblet cells and increased expression of selected tight junction proteins in the gut and brain. The gut microbiome status revealed a significant decrease in the microbial diversity in the SD rats, especially in probiotics. By contrast, a fish oil-based diet reversed SD-induced behavioral changes and improved the epithelial barrier injury and dysbiosis of the microbiota in the colon. These findings could be attributable to the increase in probiotics and short-chain fatty acid (SCFAs) production, improvement in selected intestinal barrier proteins, increase in SCFA receptor expression, and decrease in blood circulation proinflammatory status due to fish oil supplementation.

Pathological Manifestations of Francisella orientalis in the Green Texas Cichlid (Herichthys cyanoguttatus).

Francisella orientalis (Fo) is considered to be one of the major pathogens of tilapia because of the high mortalities observed during outbreaks. Other cichlids belonging to the same family (Cichlidae) as tilapia are also quite susceptible to this pathogen. On various occasions, Fo has also been isolated from other warm water fish, including three-line grunt, hybrid striped bass, French grunt, Caesar grunt, and Indo-Pacific reef fish. However, only a few studies have reported the pathogenicity of Francisella orientalis in ornamental cichlid fish. This study fulfills Koch's postulates by showing that a strain of Fo obtained from green Texas cichlid (Herichthys cyanoguttatus) was able to produce the same pathogenicity in healthy fish. A mortality of 100% was observed after healthy green Texas cichlid were experimentally injected with Fo at a dose of 8.95 × 105 CFU/fish. DNA extracted from the organs of predilection (spleen, head kidney) gave positive results by PCR for all fish that died during the experimental period. Spleen and head kidney presented with multifocal white nodules in the affected fish, corresponding to typical vacuolated granulomas on histopathological examination of the tissues. Based on the results of this study, it is evident that Fo can indeed infect green Texas cichlid and produce a disease typical of francisellosis.

The Impacts of Reassortant Avian Influenza H5N2 Virus NS1 Proteins on Viral Compatibility and Regulation of Immune Responses.

Avian influenza virus (AIV) can cause severe diseases in poultry worldwide. H6N1 AIV was the dominant enzootic subtype in 1985 in the chicken farms of Taiwan until the initial outbreak of a low pathogenic avian influenza (LPAI) H5N2 virus in 2003; thereafter, this and other LPAIs have been sporadically detected. In 2015, the outbreak of three novel H5Nx viruses of highly pathogenic avian influenza (HPAI) emerged and devastated Taiwanese chicken and waterfowl industries. The mechanism of variation in pathogenicity among these viruses is unclear; but, in light of the many biological functions of viral non-structural protein 1 (NS1), including interferon (IFN) antagonist and host range determinant, we hypothesized that NS genetic diversity contributes to AIV pathogenesis. To determine the impact of NS1 variants on viral infection dynamics, we established a reverse genetics system with the genetic backbone of the enzootic Taiwanese H6N1 for generation of reassortant AIVs carrying exogenous NS segments of three different Taiwanese H5N2 strains. We observed distinct cellular distributions of NS1 among the reassortant viruses. Moreover, exchange of the NS segment significantly influenced growth kinetics and induction of cytokines [IFN-α, IFN-ß, and tumor necrosis factor alpha (TNF-α)] in an NS1- and host-specific manner. The impact of NS1 variants on viral replication appears related to their synergic effects on viral RNA-dependent RNA polymerase activity and IFN response. With these approaches, we revealed that NS1 is a key factor responsible for the diverse characteristics of AIVs in Taiwan.

Large Area Nanoparticle Alignment by Chemical Lift-Off Lithography.

Nanoparticle alignment on the substrate attracts considerable attention due to its wide application in different fields, such as mechanical control, small size electronics, bio/chemical sensing, molecular manipulation, and energy harvesting. However, precise nanoparticle positioning and deposition control with high fidelity are still challenging. Herein, a straightforward strategy for high quality nanoparticle-alignment by chemical lift-off lithography (CLL) is demonstrated. This technique creates high resolution self-assembled monolayer (SAM) chemical patterns on gold substrates, enabling nanoparticle-selective deposition and precise alignment. The fabricated nanoparticle arrangement geometries and dimensions are well-controllable in a large area. With proper nanoparticle surface functionality control and adequate substrate molecular manipulation, well-defined nanoparticle arrays with single-particle-wide alignment resolution are achieved.