Fatty Acid Biosynthesis Pathway Research Articles

Potential anti-obesity effect of fermented adzuki beans and their untargeted metabolomics using UHPLC-QTOF-MS

Nowadays, obesity is an ultimate public health problem worldwide. However, medical and surgical treatment methods for alleviating obesity can cause multiple adverse side effects. Therefore, in the present study, we evaluated the potential anti-obesity effect of five seeds buckwheat, pea, soybean, red kidney bean, and adzuki beans cultivated in South Korea. Anti-obesity screening of seeds showed adzuki beans with the highest lipase (77.2%) and α-amylase (60.5%) inhibitory activity. Later, adzuki beans were fermented using different lactic acid bacteria (LABs). After fermentation, Pediococcus acidilactici fermented adzuki beans displayed significant anti-obesity ability, showing the half maximal inhibitory concentration (IC50) of lipase (from 1.908 to 0.839 mg/mL) and α-amylase (from 0.6873 to 0.379 mg/mL) decreased markedly compared to raw adzuki beans. UHPLC-QTOF-MS was applied to investigate metabolites and their metabolic responses during fermentation. The omics results identified 121 differentially expressed metabolites belonging to organic acids, polyphenols, amino acids and alkaloids. Furthermore, pathway enrichment revealed that P. acidilactici fermentation mainly affected fatty acid, biotin metabolism and alkaloid biosynthesis pathway, which could contribute to the promoting anti-obesity properties of adzuki beans. The metabolomics methods provide novel insights into the metabolic pathway regulation of adzuki beans in response to improving anti-obesity ability after fermentation. These findings suggest that fermenting adzuki beans with P. acidilactici might be a promising method for developing functional foods with anti-obesity properties.

Relationship between 4-Hydroxynonenal (4-HNE) as Systemic Biomarker of Lipid Peroxidation and Metabolomic Profiling of Patients with Prostate Cancer.

An oxidative degradation product of the polyunsaturated fatty acids, 4-hydroxynonenal (4-HNE), is of particular interest in cancer research due to its concentration-dependent pleiotropic activities affecting cellular antioxidants, metabolism, and growth control. Although an increase in oxidative stress and lipid peroxidation was already associated with prostate cancer progression a few decades ago, the knowledge of the involvement of 4-HNE in prostate cancer tumorigenesis is limited. This study investigated the appearance of 4-HNE-protein adducts in prostate cancer tissue by immunohistochemistry using a genuine 4-HNE monoclonal antibody. Plasma samples of the same patients and samples of the healthy controls were also analyzed for the presence of 4-HNE-protein adducts, followed by metabolic profiling using LC-ESI-QTOF-MS and GC-EI-Q-MS. Finally, the analysis of the metabolic pathways affected by 4-HNE was performed. The obtained results revealed the absence of 4-HNE-protein adducts in prostate carcinoma tissue but increased 4-HNE-protein levels in the plasma of these patients. Metabolomics revealed a positive association of different long-chain and medium-chain fatty acids with the presence of prostate cancer. Furthermore, while linoleic acid positively correlated with the levels of 4-HNE-protein adducts in the blood of healthy men, no correlation was obtained for cancer patients indicating altered lipid metabolism in this case. The metabolic pathway of unsaturated fatty acids biosynthesis emerged as significantly affected by 4-HNE. Overall, this is the first study linking 4-HNE adduction to plasma proteins with specific alterations in the plasma metabolome of prostate cancer patients. This study revealed that increased 4-HNE plasma protein adducts could modulate the unsaturated fatty acids biosynthesis pathway. It is yet to be determined if this is a direct result of 4-HNE or whether they are produced by the same underlying mechanisms. Further mechanistic studies are needed to grasp the biological significance of the observed changes in prostate cancer tumorigenesis.

Impact of Visceral Obesity on Structural and Functional Alterations of Gut Microbiota in Polycystic Ovary Syndrome (PCOS): A Pilot Study Using Metagenomic Analysis.

We aimed to identify structural and functional alterations of gut microbiota associated with visceral obesity in adult women with polycystic ovary syndrome (PCOS). Twenty-seven adults with PCOS underwent stool and fasting blood collection, oral glucose tolerance testing, and visceral fat area (VFA) measurement via dual-bioimpedance technique. Metagenomic analysis was used to analyze gut microbiota. PCOS patients were divided into three groups: visceral obesity group (PCOS-VO, n=9, age 28.33±5.68 years, BMI 37.06±4.27 kg/m2, VFA 128.67±22.45 cm2), non-visceral obesity group (PCOS-NVO, n=10, age 25.40±4.53, BMI 30.74±3.95, VFA 52.00±24.04), normal BMI group (PCOS-NB, n=8, age 27.88±2.53, BMI 21.56±2.20, VFA 27.00±21.18), with no statistical difference in age (P>0.05) and significantly statistical differences in BMI and VFA (P<0.05). The groups showed a significant difference in microbial β-diversity between PCOS-VO and PCOS-NVO (P=0.002) and no difference between PCOS-NVO and PCOS-NB (P=0.177). Bacteroidetes was the phylum with the highest relative abundance among all patients, followed by Firmicutes. Those with visceral obesity had a higher abundance of Prevotella, Megamonas, and Dialister genera, positively correlated with metabolic markers (r>0.4, P<0.05), and lower abundance of Phascolarctobacterium and Neisseria genera, negatively correlated with metabolic markers (r<-0.4, P<0.05). Functional annotation analysis showed significant differences in relative abundance of ribosome pathway, fatty acid biosynthesis pathway, and sphingolipid signaling pathway between groups, affecting lipid homeostasis and visceral fat accumulation. Alteration in β-diversity of gut microbiota exists in PCOS with visceral obesity versus those without visceral obesity and relates to functional differences in ribosomes, fatty acid biosynthesis, and sphingolipid signaling pathways.

Identification of Potential Dipeptide Inhibitors for PfENR Enzyme in Fatty Acid Biosynthesis Pathway II: A Computational Study for Developing Novel Antimalarials

Identification of Potential Dipeptide Inhibitors for PfENR Enzyme in Fatty Acid Biosynthesis Pathway II: A Computational Study for Developing Novel Antimalarials

Identification and Functional Analysis of Acyl-Acyl Carrier Protein Δ9 Desaturase from Nannochloropsis oceanica.

The oleaginous marine microalga Nannochloropsis oceanica strain IMET1 has attracted increasing attention as a promising photosynthetic cell factory due to its unique excellent capacity to accumulate large amounts of triacylglycerols and eicosapentaenoic acid. To complete the genomic annotation for genes in the fatty acid biosynthesis pathway of N. oceanica, we conducted the present study to identify a novel candidate gene encoding the archetypical chloroplast stromal acyl-acyl carrier protein Δ9 desaturase. The full-length cDNA was generated using rapid-amplification of cDNA ends, and the structure of the coding region interrupted by four introns was determined. The RT-qPCR results demonstrated the upregulated transcriptional abundance of this gene under nitrogen starvation condition. Fluorescence localization studies using EGFP-fused protein revealed that the translated protein was localized in chloroplast stroma. The catalytic activity of the translated protein was characterized by inducible expression in Escherichia coli and a mutant yeast strain BY4389, indicating its potential desaturated capacity for palmitoyl-ACP (C16:0-ACP) and stearoyl-ACP (C18:0-ACP). Further functional complementation assay using BY4839 on plate demonstrated that the expressed enzyme restored the biosynthesis of oleic acid. These results support the desaturated activity of the expressed protein in chloroplast stroma to fulfill the biosynthesis and accumulation of monounsaturated fatty acids in N. oceanica strain IMET1.

Inulin and Chinese Gallotannin Affect Meat Quality and Lipid Metabolism on Hu Sheep.

The aim of this study was to investigate the impacts of inulin and Chinese gallotannin on the meat fatty acids and urinary metabolites in sheep. Twenty-four healthy (25.80 ± 3.85 kg) weaned Hu lambs of approximately 4.5 months old were equally divided into four groups: control group (basal diet), treatment group I (basal diet + 0.1% inulin), treatment group II (basal diet + 0.1% inulin + 2% Chinese gallotannin), and treatment group III (basal diet + 0.1% inulin + 2% Chinese gallotannin + 4% PEG). The contents of myristic acid (C14:0) and palmitic acid (C16:0) were found to be lower in treatment group II than in the control group (p < 0.05). Moreover, the palmitoleic acid (C16:1) content in treatment group II was notably higher than that in the control group (p < 0.05), while the elaidic acid (C18:1n9t) content in treatment group II was higher than that in other groups (p < 0.05). Besides, the linoleic acid (C18:2n6c) content was higher in the treatment II and control groups than in the treatment I and III groups. Furthermore, compared with the control group, both 4-pyridoxic acid and creatinine in treatment groups I and II were upregulated (p < 0.05), while other metabolites, such as nicotinuric acid, l-threonine, palmitic acid, and oleic acid, were drastically downregulated (p < 0.05). These differential metabolites were found to be mainly involved in nicotinate and nicotinamide metabolism (ko00760), vitamin B6 metabolism (ko00750), and the fatty acid biosynthesis pathway (ko00061). It is concluded that the combination of inulin and Chinese gallotannin in the diet could improve the energy and lipid metabolism of sheep, which may improve both mutton quality and production performance.

Hybrid electron donors of ethanol and lactate stimulation chain elongation in microbial electrosynthesis with different inoculants

Microbial electrosynthesis (MES) is a new technology that uses electrically driven biocatalysts to convert CO2 into valuable chemicals. However, C2 as the primary product limits the development of MES. To address this issue, ethanol and lactate as additional electron donor (ED) were introduced into MES systems with different inoculants (anaerobic sludge and sediment) for chain elongation. The hybrid EDs in MES with sediment can produce the highest concentrations of butyrate (6.30 g/L) and caproate (1.60 g/L), and the corresponding total electron recovery efficiency reached the maximum value (94.51 ± 1.04%). Hybrid EDs not only provided sufficient reducing force, but also enhanced the gas mass transfer rate by releasing CO2 from lactate in situ. Metagenomic analysis showed that reverse β-oxidation pathway and fatty acid biosynthesis pathway were the main pathways. This study demonstrated that the addition of ethanol and lactate is promising method for improving the performance of MES.

Treatment with EV-miRNAs Alleviates Obesity-Associated Metabolic Dysfunction in Mice

Most cells release extracellular vesicles (EVs) that can be detected circulating in blood. We and others have shown that the microRNA contents of these vesicles induce transcriptomic changes in acceptor cells, contributing to the adjustment of metabolic homeostasis in response to environmental demands. Here, we explore the potential for modulating obesity- and exercise-derived EV-microRNAs to treat the metabolic dysfunction associated with obesity in mice. Treatment with EV-miRNAs alleviated glucose intolerance and insulin resistance in obese mice to an extent similar to that of high-intensity interval training, although only exercise improved cardiorespiratory fitness and decreased body weight. Mechanistically, EV-miRNAs decreased fatty acid and cholesterol biosynthesis pathways in the liver, reducing hepatic steatosis and increasing insulin sensitivity, resulting in decreased glycemia and triglyceridemia. Our data suggest that manipulation of EV-miRNAs may be a viable strategy to alleviate metabolic dysfunction in obese and diabetic patients who are unable to exercise, although actual physical activity is needed to improve cardiorespiratory fitness.

Flavor production in fermented chayote inoculated with lactic acid bacteria strains: Genomics and metabolomics based analysis

In this study, genomics and metabolomics were combined to reveal possible bio-synthetic pathways of core flavor compounds in pickled chayote via lactic acid bacteria (LAB) fermentation. The Lactiplantibacillus plantarum, Levilactobacillus brevis, and Lacticaseibacillus paracasei were selected as core LAB strains with better flavor-producing ability for chayote fermentation. The genomic results showed L. plantarum contained the largest number of metabolism annotated genes, while L. brevis had the fewest. Besides, the largest number of volatile compounds was detected in chayote fermented by L. plantarum, followed by L. brevis and L. paracasei. Some unique odor-active compounds (aldehydes, esters, and alcohols) and taste-active compounds (amino acids and dipeptides) were produced by different LAB strains. Accordingly, phenylalanine metabolic pathway (M00360), amino acid metabolic decomposition pathway (the Ehrlich pathway) and the anabolic pathway (the Harris pathway), and fatty acid biosynthesis pathway (M00061) were the main biosynthesis pathway involved in the flavor formation via LAB fermentation.

Quorum sensing signals stimulate biofilm formation and its electroactivity for chain elongation: System performance and underlying mechanisms

Quorum sensing signals have been widely explored in microbial communities. However, the impact of chain elongation microorganisms by quorum sensing signals of acyl homoserine lactones (AHLs) is still unclear. Here, chain elongation consortia under conditions of AHLs addition were examined in microbial electrosynthesis (MES) through 16S rRNA microbial community and metatranscriptomic analyses. The research found that N-octanoyl-L-homoserine lactone (C8-HSL) increased the caproate concentration by 61.48 % as relative to the control and showed the best performance among all the tested AHLs in MES. AHLs enhanced the redox activity of cathodic electroactive biofilms (EABs), which could be due to increased attachment of electrode microorganisms and ratios of live/dead cells. Microbial community analysis showed that AHLs increased the relative abundance of Negativicutes obviously. Meanwhile, metatranscriptomic analysis revealed that C8-HSL significantly improved CoA − transferase activity and regulated valine, leucine, isoleucine biosynthesis, and carbon metabolism. Besides, C8-HSL was beneficial to the chain elongation metabolic pathways, especially the fatty acid biosynthesis (FAB) pathway. These results not only provide metabolic insights into AHLs regulating chain elongation consortia, but also propose potential strategies for speeding up the formation of MES cathodic biofilm.

Rv2746c and Rv2881c, a potential drug target of Mycobacterium tuberculosis revealed by insilico investigation of proteins involved in lipid biosynthesis

Tuberculosis is a serious disease that requires a greater understanding of its pathophysiology to develop effective treatment strategies. To gain a better understanding of mycobacterial physiology, researchers are focusing on the key components associated with cell wall synthesis. Although mycolic and fatty acids are the primary lipid components of the mycobacterial cell envelope, understanding the proteins involved in the lipid biosynthesis pathway may open up new avenues for fundamental research. This research included a thorough computational examination of proteins from the fatty acid biosynthesis pathways. Rv2881c and Rv2764c are essential genes for lipid synthesis. It is a potential drug target because knocking out these genes has an impact on Mtb growth. The study's findings provide researchers with specific cues and concrete information that can be applied in a variety of biotechnological applications.

Biosynthesis of the multifunctional isopropylstilbene in Photorhabdus laumondii involves cross-talk between specialized and primary metabolism

Isopropylstilbene (IPS) derived from the entomopathogenic bacterium Photorhabdus represents the only known stilbene which is not produced by a plant stilbene synthase but a bacterial PKS II synthase. While the exclusive cyclization reaction, responsible for the formation of the characteristic iso-branched side-chain of the molecule, was studied in the past, some parts of the biosynthetic route remained elusive. In this study, we revealed the role of StlB that is able to produce CoA-derivatives and demonstrated the elongation of cinnamoyl-CoA with enzymes from the bacterial fatty acid biosynthesis pathway. Thus, we deciphered cross-talk between the enzymes from primary and specialized metabolism. These insights led, for the first time, to the production of IPS in a heterologous host.

Fatty Acid Biosynthesis Pathways Are Downregulated during Stigma Development and Are Critical during Self-Incompatible Responses in Ornamental Kale.

In Brassicaceae, the papillary cells of the stigma are the primary site of the self-incompatibility (SI) responses. SI preserves the genetic diversity by selectively rejecting irrelevant or incompatible pollen, thus promoting cross fertilization and species fitness. Mechanisms that regulate SI responses in Brassica have been studied mainly on the mature stigma that often undermines how stigma papillary cells attain the state of SI during development. To understand this, we integrated PacBio SMRT-seq with Illumina RNA-seq to construct a de novo full-length transcriptomic database for different stages of stigma development in ornamental kale. A total of 48,800 non-redundant transcripts, 31,269 novel transcripts, 24,015 genes, 13,390 alternative splicing, 22,389 simple sequence repeats, 21,816 complete ORF sequences, and 4591 lncRNAs were identified and analyzed using PacBio SMRT-seq. The Illumina RNA-seq revealed 15,712 differentially expressed genes (DEGs) and 8619 transcription factors. The KEGG enrichment analysis of 4038 DEGs in the "incompatibility" group revealed that the flavonoid and fatty acid biosynthesis pathways were significantly enriched. The cluster and qRT-PCR analysis indicated that 11 and 14 candidate genes for the flavonoid and fatty acid biosynthesis pathways have the lowest expression levels at stigma maturation, respectively. To understand the physiological relevance of the downregulation of fatty acid biosynthesis pathways, we performed inhibitor feeding assays on the mature stigma. The compatible pollination response was drastically reduced when mature stigmas were pre-treated with a fatty acid synthase inhibitor. This finding suggested that fatty acid accumulation in the stigmas may be essential for compatible pollination and its downregulation during maturity must have evolved as a support module to discourage the mounting of self-incompatible pollen.

Transcriptomic Interaction between Young Fecal Transplantation and Perfluorobutanesulfonate in Aged Zebrafish Gonads.

The transfer of young fecal microbiota has been found to significantly refresh the reproductive endocrine system and effectively ameliorate the toxicity of perfluorobutanesulfonate (PFBS) in aged zebrafish recipients. However, the mechanisms underlying the antagonistic action of young fecal microbiota against the reproductive endocrine toxicity of PFBS remain largely unknown. In this study, the aged zebrafish were transplanted with feces from young donors and then exposed to PFBS for 14 days. After exposure, the shift in the transcriptomic fingerprint of the gonads was profiled by using high-throughput sequencing, aiming to provide mechanistic clues into the interactive mode of action between young fecal transplantation and PFBS's innate toxicity. The results showed that the gene transcription pattern associated with protein and lipid synthesis in the gonads of the aged individuals was quite different from the young counterparts. It was intriguing that the transplantation of young feces established a youth-like transcriptomic phenotype in the elderly recipients, thus attenuating the functional decline and maintaining a healthy aging state of the gonads. A sex specificity response was clearly observed. Compared to the aged females, more metabolic pathways (e.g., glycine, serine, and threonine metabolism; glyoxylate and dicarboxylate metabolism; pyrimidine metabolism) were significantly enriched in aged males receiving young feces transplants. PFBS dramatically altered the transcriptome of aged testes, while a much milder effect was observable in aged ovaries. Accordingly, a suite of biological processes related to germ cell proliferation were disrupted by PFBS in aged males, including the ECM-receptor interaction, retinol metabolism, and folate biosynthesis. In aged ovaries exposed to PFBS, mainly the fatty acid and arginine biosynthesis pathway was significantly affected. However, these transcriptomic disorders caused by PFBS were largely mitigated in aged gonads by transferring young feces. Overall, the present findings highlighted the potential of young fecal transplantation to prevent the functional compromise of gonads resulting from aging and PFBS.

Tailored designing of a diploid S. cerevisiae natural isolate for increased production of fatty acid ethyl ester

Developing microbial chassis for synthesizing value-added compounds is the most eco-friendly approach to minimize the impacts of overusing fossil fuels and other harsh chemicals. Recent research has focussed on harnessing microbial fatty acid metabolism to generate oleochemicals for use in industries as diverse as fuel production, cosmetics, lubricants and more. Considering the economic viability of generating “green biocatalysts”, we reconfigured the fatty acid biosynthesis pathway in an environmentally robust strain of Saccharomyces cerevisiae MTCC4796 to produce fatty acid ethyl ester (FAEE) with high yield and titer. We applied the push–pull-block strategy wherein a heterologous wax ester synthase (WS2) was initially integrated to establish a FAEE biosynthetic pathway (pull) with additional rewiring including overexpression of PDH-bypass pathway genes for increasing the supply of precursor fatty acyl-CoA (push) and single allele disruption of non-essential genes from competing pathways (block) to maximize the metabolic flux towards FAEE overproduction. Our final engineered strain NGYT carrying 11 genetic modifications produced 26 mg/L and 1 g/L of FAEE before and after glucose optimization respectively. This titer was further scaled-up to reach 5 g/L in fed-batch bioreactors, which, to our knowledge, is the highest reported FAEE titer achieved from Saccharomyces cerevisiae with glucose as carbon source. Additionally, the FAEE’s produced by NGYT strain showed a higher percentage of monounsaturated fatty acids, which are ideally suitable for biodiesel applications. Given the global emphasis on the development of cleaner fuels, the findings from this study expedite our progress towards industrial scale-FAEE production as a substitute to conventional diesel.

Expression of the Fab enzymes (Fab I and Fab Z) from Plasmodium falciparum after exposure to Artemisia afra plant extracts and drugs screening.

The emergence and spread of drug resistance of the malaria parasite to the main treatment emphasize the need to develop new antimalarial drugs. In this context, the fatty acid biosynthesis (FAS_II) pathway of the malaria parasite is one of the ideal targets due to its crucial role in parasite survival. In this study, we report the expression and the affinity binding of Fab_I and Fab_Z after exposure to the parasite with different extracts of the Artemisia afra. The parasites were exposed for 2days to different extracts. Gene expression was done to determine the level of expression of the fab enzymes after treatments. A GCMS was run to determine the different compounds of the plant extracts, followed by a virtual screening between the fab enzymes and the active compounds using Pyrex. The results showed different expression patterns of the Fab enzymes. Fab_I expression was downregulated in the W2 and D6 strains by the ethanolic extract but was increased by Hexane and DCM extracts. A different expression pattern was observed for Fab_Z. It was all upregulated except in the D6 strain when exposed to the ethanolic and hexane extracts. Virtual screening showed an affinity with many compounds. Hits compounds with high binding energy were detected. 11alphaHydroxyprogesterone and Aspidospermidin-17-ol were found to have high binding energy with Fab_I respectively (-10.7kcal/mol; -10.2kcal/mol). Fab_Z shows also high affinity with 11alpha-Hydroxyprogesterone (-10kcal/mol) and Thiourea (-8.4kcal/mol). This study shows the potential of A. afra to be used as a new source of novel antimalarial compounds.

Genome-wide identification of fatty acid synthesis genes, fatty acid profiles, and life parameters in two freshwater water flea Daphnia magna strains.

The freshwater water flea Daphnia magna is a planktonic animal belonging to the Cladocera. To evaluate differences between two D. magna strains (KIT and NIES) in terms of life parameters and fatty acid profiles, we examined several endpoints. In the D. magna KIT strain, the numbers of total and cumulative offspring were lower at 23 °C and higher at 14 °C than in the D. magna NIES strain. However, at 14 °C, the D. magna KIT strain showed an increased lifespan. Although the n-3/n-6 polyunsaturated fatty acids (PUFA) ratio was always decreased at a low temperature, the PUFA ratio in the KIT strain had a higher value on day 3 than the NIES strain, which gave it higher adaptability to low temperature. In addition, we identified the elongation of very long chain fatty acids (elovl) and fatty acid desaturase (fad) genes, which are involved in fatty acid biosynthesis pathways, in the genomes of both D. magna KIT and NIES. The Elovl and Fad genes in both D. magna strains were highly conserved, including tandem duplicated Elovl 1/7 genes. This study provides new information about the molecular basis for the difference in temperature sensitivity between two strains of D. magna.

Overexpression of WRINKLED1 improves the weight and oil content in seeds of flax (Linum usitatissimum L.).

Seeds of flax (Linum usitatissimum L.) are highly rich in both oil and linolenic acid (LIN). It is crucial for flax agricultural production to identify positive regulators of fatty acid biosynthesis. In this study, we find that WRINKLED1 transcription factors play important positive roles during flax seed oil accumulation. Two WRINKLED1 genes, LuWRI1a and LuWRI1b, were cloned from flax, and LuWRI1a was found be expressed predominantly in developing seeds during maturation. Overexpression of LuWRI1a increased seed size, weight, and oil content in Arabidopsis and increased seed storage oil content in transgenic flax without affecting seed production or seed oil quality. The rise in oil content in transgenic flax seeds was primarily attributable to the increase in seed weight, according to a correlational analysis. Furthermore, overexpression or interference of LuWRI1a upregulated the expression of genes in the fatty acid biosynthesis pathway and LAFL genes, and the expression level of WRI1 was highly significantly positively associated between L1L, LEC1, and BCCP2. Our findings give a theoretical scientific foundation for the future application of genetic engineering to enhance the oil content of plant seeds.

Sex-specific analysis of microRNA profiles in HBV-associated cirrhosis by small RNA-sequencing.

Liver cirrhosis represents an advanced stage of chronic liver disease and is associated with significant morbidity, mortality, and risk of cancer development. While sex disparity of liver diseases has been observed, understanding at a genetic level awaits more thorough investigation. In this study, we performed a sex-specific analysis of the microRNA (miR) profiles in hepatitis B virus (HBV)-associated cirrhosis by small RNA-sequencing using clinical tissue samples. Potential associated signaling pathways, downstream gene targets, and upstream regulators were highlighted by computational prediction analyses based on the differentially expressed miRs (DEmiRs). From our results, deregulation of miRs in cirrhosis showed a marked difference between males and females by the degree and pattern. Sixty-five (64 up-regulated, 1 down-regulated) and 12 (6 up-regulated, 6 down-regulated) DEmiRs were found in males and females, respectively, when compared with their respective control group. A number of DEmiRs were only observed in one sex but not the other. In addition, 26 DEmiRs were identified between cirrhosis female and cirrhosis male groups. Fatty acid biosynthesis pathway, extracellular matrix-receptor interaction, p53 signaling, Hippo signaling, tumor necrosis factor signaling, the forkhead box O signaling, as well as gene targets ribosomal protein S27 like, methyl CpG binding protein 2, and estrogen receptor 1, may contribute to the pathogenesis and biological behavior of cirrhosis in a sex-specific manner. Analysis of the Cancer Genome Atlas data set suggested a role of sex-specific DEmiRs in multistep hepatocarcinogenesis. Conclusion: Our findings illustrate that miR profiles in HBV-associated cirrhosis are distinct between the males and females and suggest a potential role of sex-specific biomarkers and molecular mechanisms in disease development and progression.

Integrative functional analysis uncovers metabolic differences between Candida species.

Candida species are a dominant constituent of the human mycobiome and associated with the development of several diseases. Understanding the Candida species metabolism could provide key insights into their ability to cause pathogenesis. Here, we have developed the BioFung database, providing an efficient annotation of protein-encoding genes. Along, with BioFung, using carbohydrate-active enzyme (CAZymes) analysis, we have uncovered core and accessory features across Candida species demonstrating plasticity, adaption to the environment and acquired features. We show a greater importance of amino acid metabolism, as functional analysis revealed that all Candida species can employ amino acid metabolism. However, metabolomics revealed that only a specific cluster of species (AGAu species—C. albicans, C. glabrata and C. auris) utilised amino acid metabolism including arginine, cysteine, and methionine metabolism potentially improving their competitive fitness in pathogenesis. We further identified critical metabolic pathways in the AGAu cluster with biomarkers and anti-fungal target potential in the CAZyme profile, polyamine, choline and fatty acid biosynthesis pathways. This study, combining genomic analysis, and validation with gene expression and metabolomics, highlights the metabolic diversity with AGAu species that underlies their remarkable ability to dominate they mycobiome and cause disease.