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Suitability of using sieved or unsieved maize mash for production of "OGI"--a fermented cereal food.

Proximate analysis of sieved and unsieved maize mash revealed that there was a decrease in the protein and lipid content of the sieved maize mash as compared to that of the unsieved maize mash. Crude fibre and ash was completely absent in the sieved maize mash, while they were present in the unsieved mash. Chemical analysis of the fermented unsieved maize mash revealed an increase in the protein content from 9.9% (unfermented) to 13.4% after 3 days of fermentation, whereas the protein content of the sieved maize mash increased from 7.1% (unfermented) to 8.4% after the same period of fermentation. Furthermore, the results revealed that the protein content of the fermented unsieved maize mash was 32.1% higher than that of the fermented sieved maize mash indicating that the unsieved maize mash was of a better nutrient quality and should be preferred to sieved maize mash for use in "Ogi" production.

Carbohydrates

A refined MASH-HCC model identifies macrophage Gadd45b as a key orchestrator of inflammation-driven neoplastic progression.

Metabolic dysfunction-associated steatohepatitis (MASH) is emerging as a leading driver of hepatocellular carcinoma (HCC), yet the molecular mechanisms linking metabolic stress, chronic inflammation and tumorigenesis remain poorly understood. Here we established a metabolically relevant, time-efficient MASH-to-HCC model in C57BL/6N mice by combining a MASH diet with controlled CCl4 administration, enabling stepwise recapitulation of MASH-associated neoplastic progression. Using this model, we identified growth arrest and DNA damage 45b (Gadd45b) as a novel MASH-derived protumorigenic regulator selectively activated under metabolic stress. Integrated analyses of human bulk and single-cell transcriptomic datasets and mouse transcriptomic deconvolution revealed concordant macrophage remodeling and GADD45B/Gadd45b expression dynamics during MASH-to-HCC progression. Mechanistically, fatty acids and TNFα preferentially induced Gadd45b in macrophages, where it amplified TNFα-NF-κB signaling. Macrophage-derived inflammatory signals subsequently induced Gadd45b and NF-κB activation in hepatocytes, establishing a feed-forward inflammatory loop that promoted fibrogenic and partial EMT-like programs and tumor spheroid formation. Importantly, temporal profiling during spheroid formation and progression revealed transient induction of Gadd45b during early spheroid establishment, but not during later progression, indicating that Gadd45b-mediated inflammatory signaling primarily promotes tumor initiation rather than subsequent growth. Consistent with human data, Gadd45b expression increased with disease severity and positively correlated with inflammatory factors in the MASH-HCC model, whereas pharmacological inhibition attenuated the Gadd45b-inflammation signaling axis. Collectively, our findings establish macrophage Gadd45b as a key orchestrator linking metabolic stress, chronic inflammation, and neoplastic transformation during MASH-to-HCC progression. Our refined MASH-HCC model provides a robust platform for mechanistic studies and preclinical evaluation of inflammation-targeted therapies.

Journal Article

Deletion of hepatic FXR leads to more severe MASH development in female mice.

BACKGROUND: The farnesoid X receptor (FXR) has been identified as a therapeutic target for metabolic dysfunction-associated steatohepatitis (MASH). FXR is the major homeostatic regulator of bile acids (BAs) with dysregulation of BAs and/or FXR implicated in the pathogenesis of MASH. Synthetic whole-body FXR agonists have been developed to treat MASH. Although beneficial for MASH treatment, these whole-body modulators contribute to unfavorable side effects such as pruritus and an elevation in low-density liporoteins, thereby highlighting the importance of tissue and cell-restricted modulation of FXR in the development of novel therapeutics for MASH to negate potential harmful off-target effects. METHODS: The objective of this study was to determine the tissue-specific role of FXR in MASH development using male and female wild-type (WT), liver FXR KO (FXRhep-/-), intestinal FXR KO (FXRint-/-), and whole body FXR KO (FXR KO) mice fed either a low-fat control diet (CTL) or a MASH "Fast Food" (FF) diet. RESULTS: The results showed, in females, hepatic, but not intestinal, deficiency of FXR was associated with severe liver injury, through increased ALT, ALP, and genes indicative of inflammation and fibrosis when comparing FXRhep-/- versus FXRint-/-. Regardless of sex, hepatic FXR deficiency triggered the activation of neuroinflammation and neurodegenerative canonical pathways. CONCLUSIONS: These data suggest that hepatic FXR is more critical in suppressing liver injury during MASH development in female mice. However, this same trend was not clear in the male cohorts, highlighting sex differences and potential roles for sexual dimorphism in MASH development.

Animals

[Application HTST-heating of the mash and its influence on the aroma composition during the production of apple brandy (author's transl)].

The influence of HTST-heating of the mash aroma composition during production of apply brandy has been investigated by means of gas chromatography and coupled gas chromatography--mass spectrometry. Starting from the apple aroma the changes in aroma components were studied quantitatively during the conventional production (without enzyme inhibition) as well as after HTST-heating (enzyme inactivation) of the mash. For this purpose 98 aroma compounds were determined in the course of mash production, fermentation and distillation. When employing HTST-heating the original aroma components of the apple particularly the fruit esters were present in appreciably higher concentrations in the mash as well as in the distillate than with the conventional production method. Simultaneously HTST-heating reduced the secondary aroma substances in mash and distillate which are formed with the conventional method by enzymatic-oxidative processes. In the unaged apple brandy obtained from HTST-treated mash lower amounts of lactates and higher concentrations of acetals were found compared with the conventionally produced distillate.

Acetates

Relationship of low lysine and high arginine concentrations to efficient ethanolic fermentation of wheat mash.

Very high gravity wheat mashes containing 20 or more grams of carbohydrates per 100 mL were fermented completely by Saccharomyces cerevisiae, even though these mashes contained low amounts of assimilable nitrogen. Supplementation of wheat mashes with various amino acids or with yeast extract, urea, or ammonium sulfate reduced the fermentation time. However, lysine or glycine added as single supplements, inhibited yeast growth and fermentation. With lysine, yeast growth was severely inhibited, and a loss of cell viability as high as 80% was seen. Partial or complete reversal of lysine-induced inhibition was achieved by the addition of a number of nitrogen sources. All nitrogen sources that relieved lysine-induced inhibition of yeast growth also promoted uptake of lysine and restored cell viability to the level observed in the control. They also increased the rate of fermentation. Experiments with minimal media showed that for lysine to be inhibitory to yeast growth, assimilable nitrogen in the medium must be in growth-limiting concentrations or totally absent. In the presence of excess nitrogen, lysine stimulated yeast growth and fermentation. Results indicate that supplementing wheat mash with other nitrogen sources increases the rate of fermentation not only by providing extra nitrogen but also by reducing or eliminating the inhibitory effect of lysine on yeast growth.

Arginine

DNA binding and transcriptional regulatory activity of mammalian achaete-scute homologous (MASH) proteins revealed by interaction with a muscle-specific enhancer.

The MASH genes are vertebrate homologues of achaete-scute, genes required for neuronal determination in Drosophila. The sequence of MASH1 and MASH2 contains a basic helix-loop-helix (bHLH) motif that is present in other transcriptional regulators such as MyoD and E12. In the absence of an authentic target for the MASH proteins, we examined their DNA binding and transcriptional regulatory activity by using a binding site (the E box) from the muscle creatine kinase (MCK) gene, a target of MyoD. Like myogenic bHLH proteins, the MASH proteins form heterooligomers with E12 that bind the MCK E box with high affinity in vitro. Unexpectedly, however, MASH1 and MASH2 also activate transcription of both exogenous and endogenous MCK in transfected C3H/10T1/2 fibroblasts. However, they do not induce myogenesis. Myogenic activity is not exclusively a property of the MyoD basic region, as substitution of this domain fails to confer myogenic activity on MASH1. These data suggest that different bHLH proteins may activate overlapping but distinct sets of target genes in the same cell type.

Amino Acid Sequence

Effect of germination on the glycoprotein of mash (Phaseolus mungo) seeds.

The soluble carbohydrates and insolube proteins of Phaseolus mungo seeds decreased considerably up to 96 h of germination, whereas the soluble proteins remained nearly constant. The carbohydrates content of glycoprotein also remained constant. This suggests that a negligible change took place in the glycoprotein during the initial period of mash seed germination.

Carbohydrates

Research note: effects of beak trimming and genetic stock on rate of mash consumption and feeding-related behavior in egg-strain pullets.

Pullets whose beaks were trimmed once (at 9 days) and twice (at 9 days and 9 wk) were able to ingest feed, in the form of mash, more rapidly under competitive feeding conditions and at least as rapidly in the absence of competition as pullets with intact beaks. Tests of feeding rate, when pullets fed in groups, were carried out after a feed deprivation period of 7 h at ages of 10 through 16 wk. Similar tests were done at 18 wk, when pullets fed without competition. Genetic stock and age had significant effects on frequency of agonistic acts at the feeder and displacements from the feeder during 5-min tests under competitive feeding conditions. Age influenced the number of pullets feeding simultaneously and amount of feed eaten per pullet during the same feeding tests. No interactions were detected among beak treatment, stock, and age for feeding-related behaviors or rate of feed consumption during competitive feeding. In noncompetitive feeding tests, genetic stock affected feeding rate but no stock by beak treatment interaction was present.

Aging

Orthopedic experience in a MASH unit in postwar Iraq.

The orthopedic experience of a U.S. Army MASH unit deployed in southern Iraq is discussed. Seventy major casualties were surgically treated in a short time span. A high percentage of extremity trauma was observed (69%). Many patients had multiple extremity involvement. The emergency wartime surgical treatment of four specific types of trauma is explored. A new algorithm is presented for the rapid evaluation of penetrating joint injuries. We summarize the current concepts of war surgery as they apply to orthopedic injuries, and add specific observations from this experience.

Hospitals, Military

Induction and repression of mammalian achaete-scute homologue (MASH) gene expression during neuronal differentiation of P19 embryonal carcinoma cells.

MASH1 and MASH2, mammalian homologues of the Drosophila neural determination genes achaete-scute, are members of the basic helix-loop-helix (bHLH) family of transcription factors. We show here that murine P19 embryonal carcinoma cells can be used as a model system to study the regulation and function of these genes. MASH1 and MASH2 display complementary patterns of expression during the retinoic-acid-induced neuronal differentiation of P19 cells. MASH1 mRNA is undetectable in undifferentiated P19 cells but is induced to high levels by retinoic acid coincident with neuronal differentiation. In contrast, MASH2 mRNA is expressed in undifferentiated P19 cells and is repressed by retinoic acid treatment. These complementary expression patterns suggest distinct functions for MASH1 and MASH2 in development, despite their sequence homology. In retinoic-acid-treated P19 cells, MASH1 protein expression precedes and then overlaps expression of neuronal markers. However, MASH1 is expressed by a smaller proportion of cells than expresses such markers. MASH1 immunoreactivity is not detected in differentiated cells displaying a neuronal morphology, suggesting that its expression is transient. These features of MASH1 expression are similar to those observed in vivo, and suggest that P19 cells represent a good model system in which to study the regulation of this gene. Forced expression of MASH1 was achieved in undifferentiated P19 cells by transfection of a cDNA expression construct. The transfected cells expressing exogenous MASH1 protein contained E-box-binding activity that could be super-shifted by an anti-MASH1 antibody, but exhibited no detectable phenotypic changes. Thus, unlike myogenic bHLH genes, such as MyoD, which are sufficient to induce muscle differentiation, expression of MASH1 appears insufficient to promote neurogenesis.

Animals

Genome-wide DNA methylation profiling during metabolic dysfunction-associated steatohepatitis-related hepatocarcinogenesis in patients in Japan and the United States.

This study aimed to compare ethnicity-related differences in DNA methylation profiles during metabolic dysfunction-associated steatohepatitis (MASH)-related hepatocarcinogenesis in patients from Japan and the United States (US). Genome-wide DNA methylation analysis using the Infinium assay was performed in 36, 148 and 36 samples of normal liver tissue (NLT), non-cancerous liver tissue showing MASH, and MASH-related hepatocellular carcinoma (HCC), respectively (220 samples in total), from the Japan and US cohorts. Principal component analysis revealed that MASH had a distinct DNA methylation profile differing from that of NLT, and that the MASH profiles in the two cohorts differed from each other. DNA methylation alterations of cancer-related genes in MASH were inherited by or strengthened in MASH-related HCC itself, resulting in expression alterations. DNA methylation alterations of FGFR2, FUT4, B3GNT5 and MOSC1 in the precancerous MASH stage were shared by the two cohorts, suggesting that such genes are commonly associated with MASH-related hepatocarcinogenesis. On the other hand, it was suggested that DNA methylation alterations of ZNF611 and SAMD10, and those of SHC1, are involved specifically in MASH-related hepatocarcinogenesis in the Japan and the US cohorts, respectively. These findings suggest that DNA methylation alterations, which may reflect race and lifestyle, are associated with MASH-related hepatocarcinogenesis.

Humans