-
Marine Drugs May 2024Recently, there has been a growing interest in collagen peptides derived from marine sources for their notable ability to protect skin cells against apoptosis induced by...
Recently, there has been a growing interest in collagen peptides derived from marine sources for their notable ability to protect skin cells against apoptosis induced by oxidants. Therefore, the current study aimed to investigate the fundamental properties of collagen peptides, including their physicochemical, thermal, structural, stem-cell-regenerative, and skin-cell-protective effects, in comparison to commercial collagen peptides. The acid-soluble (ASC) and pepsin-soluble (PSC) collagens exhibited three distinct bands on SDS-PAGE, namely α (α and α), β, and γ chains, confirming a type I pattern. The thermal profiles obtained from TG and DSC analyses confirmed the denaturation of PSC and ASC at temperatures ranging from 51.94 to 56.4 °C and from 52.07 to 56.53 °C, respectively. The purified collagen peptides were analyzed using SDS-PAGE and MALDI-TOF mass spectrometry, revealing a mass range of 900-15,000 Da. Furthermore, the de novo peptide sequence analysis confirmed the presence of the Gly-X-Y repeating sequence in collagen peptides. Collagen peptide treatments significantly enhanced HFF-1 cell proliferation and migration compared to the control group. ELISA results confirmed the potential interactions between collagen peptides and HFF-1 cells through αβ, αβ, and αβ integrin receptors. Notably, collagen peptide treatment effectively restored the proliferation of HFF-1 cells damaged by HO. Consequently, the advantageous characteristics of squid skin collagen peptides highlight their promising role in regenerative medicine.
Topics: Animals; Hydrogen Peroxide; Collagen; Fibroblasts; Decapodiformes; Skin; Humans; Peptides; Cell Proliferation; Stem Cells; Cell Line; Protective Agents; Cell Movement
PubMed: 38921566
DOI: 10.3390/md22060255 -
Metabolites Jun 2024Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common condition with heterogeneous outcomes difficult to predict at the individual level. Feared... (Review)
Review
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common condition with heterogeneous outcomes difficult to predict at the individual level. Feared complications of advanced MASLD are linked to clinically significant portal hypertension and are initiated by functional and mechanical changes in the unique sinusoidal capillary network of the liver. Early sinusoidal vasoregulatory changes in MASLD lead to increased intrahepatic vascular resistance and represent the beginning of portal hypertension. In addition, the composition and function of gut microbiota in MASLD are distinctly different from the healthy state, and multiple lines of evidence demonstrate the association of dysbiosis with these vasoregulatory changes. The gut microbiota is involved in the biotransformation of nutrients, production of de novo metabolites, release of microbial structural components, and impairment of the intestinal barrier with impact on innate immune responses, metabolism, inflammation, fibrosis, and vasoregulation in the liver and beyond. The gut-liver axis is a conceptual framework in which portal circulation is the primary connection between gut microbiota and the liver. Accordingly, biochemical and hemodynamic attributes of portal circulation may hold the key to better understanding and predicting disease progression in MASLD. However, many specific details remain hidden due to limited access to the portal circulation, indicating a major unmet need for the development of innovative diagnostic tools to analyze portal metabolites and explore their effect on health and disease. We also need to safely and reliably monitor portal hemodynamics with the goal of providing preventive and curative interventions in all stages of MASLD. Here, we review recent advances that link portal metabolomics to altered sinusoidal vasoregulation and may allow for new insights into the development of portal hypertension in MASLD.
PubMed: 38921459
DOI: 10.3390/metabo14060324 -
Current Issues in Molecular Biology Jun 2024Nonalcoholic steatohepatitis (NASH) is characterized by severe inflammation and fibrosis due to an excessive accumulation of triglycerides (TGs) in the liver with a...
Nonalcoholic steatohepatitis (NASH) is characterized by severe inflammation and fibrosis due to an excessive accumulation of triglycerides (TGs) in the liver with a dysregulated de novo lipogenesis (DNL) pathway. In this study, we aimed to evaluate the effectiveness of YC-1102, an extract obtained from the roots of , as a nutritional supplement in a diet-induced NASH mouse model. C57BL/6 wild-type mice were fed a fructose, palmitate, and cholesterol (FPC)-containing diet for 16 weeks to induce experimental NASH. A daily oral gavage of YC-1102 and obetichoic acid (OCA) was conducted for 9 weeks. After sacrifice, disease parameters related to hepatic lipids, inflammation, and fibrosis were evaluated. The treatment with YC-1102 significantly decreased the liver/body weight ratio, epididymal fat weight, and plasma ALT and AST levels, which are indicators of NASH injuries. YC-1102 attenuated hepatic lipid accumulation by inhibiting the transcription of DNL genes in the livers exhibiting NASH. Additionally, we found that YC-1102 blocked the development of hepatic inflammation and fibrosis by directly disturbing macrophage activation, resulting in an amelioration of hepatic fibrosis. Our findings suggest that YC-1102 could ameliorate NASH progression by inhibiting uncontrolled DNL and inflammation.
PubMed: 38921022
DOI: 10.3390/cimb46060351 -
Antibodies (Basel, Switzerland) Jun 2024: Kidney transplantation is the preferred modality of kidney replacement therapy for eligible patients with end-stage kidney disease (ESKD), given that it has been found...
: Kidney transplantation is the preferred modality of kidney replacement therapy for eligible patients with end-stage kidney disease (ESKD), given that it has been found to reduce mortality rates, improve quality of life, and is cost-effective compared to dialysis. Recent advancements in human leukocyte antigen (HLA) typing and donor-specific antibody (DSA) detection have helped to reduce the risk of rejection, but antibody-mediated rejection (AMR) can still occur without DSA. Previous studies suggest that rejection can be attributed to antibodies against Non-Human Leucocyte Antigens (non-HLAs). We aimed to acquire further understanding of the prevalence and distribution of non-HLA antibodies in our local population and attempt to correlate these findings with graft outcomes, as well as assess whether non-HLA antibodies can be utilized to determine graft impairment and dysfunction. : We conducted a retrospective study involving kidney transplant recipients between January 2010 and December 2020. All included individuals were aged over 18 and underwent kidney-alone transplants; were ABO- and HLA-compatible; and were matched at A, B, and DR loci (mismatch 0:0:0). HLA testing was negative at the time of transplantation. The samples from both cases of early graft rejection and the control group were tested for non-HLA antibodies using One Lambda LABScreen, Autoantibody kit groups 1, 2, and 3, as well as the Immucor LIFECODES non-HLA autoantibody assay. : A total of 850 kidney transplant recipients were included, in which 12 patients experienced early graft rejection within the first month post transplant and 18 patients who did not experience graft rejection were selected as study controls. Our study reported no correlation between the total burden of non-HLA antibodies and early rejection, most likely as the result of a small sample size. Nevertheless, a sub-analysis revealed that specific high-frequency pre-transplant non-HLA antibodies such as GSTT, CXCL11, CXCL10, and HNR, detected by LIFECODES, were associated with rejection (Fisher's exact test with Bonferroni correction, < 0.001). Most pre-transplant non-HLA antibody levels were reduced after transplantation, which was attributed to immunosuppression. : The 'high frequency' non-HLA antibodies displayed an association with graft rejection, though the overall associations between the burden of non-HLA antibodies and rejection episodes remain inconclusive. Further work is needed to establish the rebound phenomenon of non-HLA antibodies, the development of de novo non-HLA antibodies in the long run, and their implications on graft survival.
PubMed: 38920968
DOI: 10.3390/antib13020044 -
MSphere Jun 2024Myriocin is an inhibitor of synthesis of sphingolipids and ceramides. In this research, we showed myriocin could significantly reduce Mtb burden and histopathological...
Myriocin is an inhibitor of synthesis of sphingolipids and ceramides. In this research, we showed myriocin could significantly reduce Mtb burden and histopathological inflammation in mice. However, the underlying mechanism remains unclear. RNA-seq analysis revealed a significant increase in gene expression of PLIN2/CD36/CERT1 after myriocin treatment. The reduced bactericidal burden was only reversed after silencing the lipid droplets (LDs) surface protein PLIN2. This suggests that myriocin enhances the ability of macrophages to clear Mtb depending on the PLIN2 gene, which is part of the PPARγ pathway. Indeed, we observed a significant increase in the number of LDs following myriocin treatment.IMPORTANCE has the ability to reprogram host cell lipid metabolism and alter the antimicrobial functions of infected macrophages. The sphingolipids, such as ceramides, are the primary host lipids utilized by the bacteria, making the sphingomyelinase/ceramide system critical in Mtb infections. Surprisingly, the antimicrobial effect of myriocin was found to be independent of its role in reducing ceramides, but instead, it depends on the lipid droplets surface protein PLIN2. Our findings provide a novel mechanism for how myriocin enhances Mtb clearance in macrophages.
PubMed: 38920406
DOI: 10.1128/msphere.00257-24 -
Biodiversity Data Journal 2024is an endemic and endangered species with significant economic and ecological value in Vietnam. A better understanding of the genetic architecture of the species will...
is an endemic and endangered species with significant economic and ecological value in Vietnam. A better understanding of the genetic architecture of the species will be useful when planning management and conservation. We aimed to characterize the transcriptome of , develop novel molecular markers, and assess the genetic variability of the species. First, transcriptome sequencing of five trees () based on root, leaf, and stem tissues was performed for functional annotation analysis and development of novel molecular markers. The transcriptomes of were analyzed via an Illumina HiSeq 4000 sequencing system. A total of 27,363,199 bases were generated for . De novo assembly indicated that a total of 160,435 unigenes were generated (average length = 548.954 bp). The 51,691 unigenes were compared against different databases, i.e. , and for functional annotation. Furthermore, a total of 12,849 EST-SSRs were identified. Of the 134 primer pairs, 54 were randomly selected for testing, with 15 successfully amplified across nine populations of . We uncovered medium levels of genetic diversity (PIC = 0.52, Na = 3.29, Ne = 2.18, P = 94.07%, H = 0.56 and He = 0.47) within the studied populations. The molecular variance was 10% among populations and low genetic differentiation (Fst = 0.06) indicated low gene flow (Nm = 2.16). A reduction in the population size of was detected using BOTTLENECK (VP population). The structure analysis suggested two optimal genetic clusters related to gene flow among the populations. Analysis of molecular variance (AMOVA) revealed higher genetic variation within populations (90%) than among populations (10%). The UPGMA approach and DAPC divided the nine populations into three main clusters. Our findings revealed a significant fraction of the transcriptome sequences and these newlydeveloped novel EST-SSR markers are a very efficient tool for germplasm evaluation, genetic diversity and molecular marker-assisted selection in . This study provides comprehensive genetic resources for the breeding and conservation of different varieties of .
PubMed: 38919771
DOI: 10.3897/BDJ.12.e123405 -
Frontiers in Immunology 2024Resection of colorectal liver metastasis is the standard of care for patients with Stage IV CRC. Despite undoubtedly improving the overall survival of patients, pHx for...
BACKGROUND
Resection of colorectal liver metastasis is the standard of care for patients with Stage IV CRC. Despite undoubtedly improving the overall survival of patients, pHx for colorectal liver metastasis frequently leads to disease recurrence. The contribution of this procedure to metastatic colorectal cancer at a molecular level is poorly understood. We designed a mouse model of orthograde metastatic colorectal cancer (CRC) to investigate the effect of partial hepatectomy (pHx) on tumor progression.
METHODS
CRC organoids were implanted into the cecal walls of wild type mice, and animals were screened for liver metastasis. At the time of metastasis, 1/3 partial hepatectomy was performed and the tumor burden was assessed longitudinally using MRI. After euthanasia, different tissues were analyzed for immunological and transcriptional changes using FACS, qPCR, RNA sequencing, and immunohistochemistry.
RESULTS
Mice that underwent pHx presented significant liver hypertrophy and an increased overall metastatic load compared with SHAM operated mice in MRI. Elevation in the metastatic volume was defined by an increase in liver metastasis without any effect on the growth of each metastasis. Concordantly, the livers of pHx mice were characterized by neutrophil and bacterial infiltration, inflammatory response, extracellular remodeling, and an increased abundance of tight junctions, resulting in the formation of a premetastatic niche, thus facilitating metastatic seeding.
CONCLUSIONS
Regenerative pathways following pHx accelerate colorectal metastasis to the liver by priming a premetastatic niche.
Topics: Animals; Colorectal Neoplasms; Hepatectomy; Mice; Liver Neoplasms; Liver; Tumor Microenvironment; Disease Models, Animal; Humans; Mice, Inbred C57BL; Inflammation; Male
PubMed: 38919609
DOI: 10.3389/fimmu.2024.1388272 -
Horticulture Research Jun 2024To date, there has been no high-quality sequence for genomes of the East Asian grape species, hindering biological and breeding efforts to improve grape cultivars. This...
To date, there has been no high-quality sequence for genomes of the East Asian grape species, hindering biological and breeding efforts to improve grape cultivars. This study presents ~522 Mb of the () genome sequence containing 27 635 coding genes. Phylogenetic analysis indicated that () may have first split from the other two species, and (). Divergent numbers of duplicated genes reserved among grapes suggests that the core eudicot-common hexaploidy (ECH) and the subsequent genome instability still play a non-negligible role in species divergence and biological innovation. Prominent accumulation of sequence variants might have improved cold resistance in , resulting in a more robust network of regulatory cold resistance genes, explaining why it is extremely cold-tolerant compared with and . In contrast, has preserved many fewer nucleotide binding site (NBS) disease resistance genes than the other grapes. Notably, multi-omics analysis identified one -cinnamate 4-monooxygenase gene positively correlated to the resveratrol accumulated during berry development. A selective sweep analysis revealed a hypothetical sex-determination region (SDR). Besides, a PPR-containing protein-coding gene in the hypothetical SDR may be related to sex determination in . The content and arrangement order of genes in the putative SDR of female were similar to those of female . However, the putative SDR of female has lost one flavin-containing monooxygenase (FMO) gene and contains one extra protein-coding gene uncharacterized so far. These findings will improve the understanding of biology and contribute to the improvement of grape breeding.
PubMed: 38919553
DOI: 10.1093/hr/uhae117 -
Biotechnology For Biofuels and... Jun 2024β-Arbutin, a hydroquinone glucoside found in pears, bearberry leaves, and various plants, exhibits antioxidant, anti-inflammatory, antimicrobial, and anticancer...
BACKGROUND
β-Arbutin, a hydroquinone glucoside found in pears, bearberry leaves, and various plants, exhibits antioxidant, anti-inflammatory, antimicrobial, and anticancer effects. β-Arbutin has wide applications in the pharmaceutical and cosmetic industries. However, the limited availability of high-performance strains limits the biobased production of β-arbutin.
RESULTS
This study established the β-arbutin biosynthetic pathway in C. glutamicum ATCC13032 by introducing codon-optimized ubiC, MNX1, and AS. Additionally, the production titer of β-arbutin was increased by further inactivation of csm and trpE to impede the competitive metabolic pathway. Further modification of the upstream metabolic pathway and supplementation of UDP-glucose resulted in the final engineered strain, C. glutamicum AR11, which achieved a β-arbutin production titer of 7.94 g/L in the optimized fermentation medium.
CONCLUSIONS
This study represents the first successful instance of de novo β-arbutin production in C. glutamicum, offering a chassis cell for β-arbutin biosynthesis.
PubMed: 38918796
DOI: 10.1186/s13068-024-02540-2 -
BMC Cancer Jun 2024High-grade B-cell lymphoma (HGBCL), the subtype of non-Hodgkin lymphoma, to be relapsed or refractory in patients after initial therapy or salvage chemotherapy. Dual...
High-grade B-cell lymphoma (HGBCL), the subtype of non-Hodgkin lymphoma, to be relapsed or refractory in patients after initial therapy or salvage chemotherapy. Dual dysregulation of MYC and BCL2 is one of the important pathogenic mechanisms. Thus, combined targeting of MYC and BCL2 appears to be a promising strategy. Dihydroorotate dehydrogenase (DHODH) is the fourth rate-limiting enzyme for the de novo biosynthesis of pyrimidine. It has been shown to be a potential therapeutic target for multiple diseases. In this study, the DHODH inhibitor brequinar exhibited growth inhibition, cell cycle blockade, and apoptosis promotion in HGBCL cell lines with MYC and BCL2 rearrangements. The combination of brequinar and BCL2 inhibitors venetoclax had a synergistic inhibitory effect on the survival of DHL cells through different pathways. Venetoclax could upregulate MCL-1 and MYC expression, which has been reported as a resistance mechanism of BCL2 inhibitors. Brequinar downregulated MCL-1 and MYC, which could potentially overcome drug resistance to venetoclax in HGBCL cells. Furthermore, brequinar could downregulate a broad range of genes, including ribosome biosynthesis genes, which might contribute to its anti-tumor effects. In vivo studies demonstrated synergetic tumor growth inhibition in xenograft models with brequinar and venetoclax combination treatment. These results provide preliminary evidence for the rational combination of DHODH and BCL2 blockade in HGBCL with abnormal MYC and BCL2.
Topics: Humans; Animals; Proto-Oncogene Proteins c-bcl-2; Dihydroorotate Dehydrogenase; Mice; Sulfonamides; Bridged Bicyclo Compounds, Heterocyclic; Proto-Oncogene Proteins c-myc; Xenograft Model Antitumor Assays; Drug Synergism; Cell Line, Tumor; Oxidoreductases Acting on CH-CH Group Donors; Apoptosis; Lymphoma, B-Cell; Gene Rearrangement; Cell Proliferation; Biphenyl Compounds; Quinaldines
PubMed: 38918775
DOI: 10.1186/s12885-024-12534-w