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Journal of Affective Disorders Aug 2024The therapeutic response to lithium in patients with bipolar disorder is highly variable and has a polygenic basis. Genome-wide association studies investigating lithium...
BACKGROUND
The therapeutic response to lithium in patients with bipolar disorder is highly variable and has a polygenic basis. Genome-wide association studies investigating lithium response have identified several relevant loci, though the precise mechanisms driving these associations are poorly understood. We aimed to prioritise the most likely effector gene and determine the mechanisms underlying an intergenic lithium response locus on chromosome 21 identified by the International Consortium on Lithium Genetics (ConLiGen).
METHODS
We conducted in-silico functional analyses by integrating and synthesising information from several publicly available functional genetic datasets and databases including the Genotype-Tissue Expression (GTEx) project and HaploReg.
RESULTS
The findings from this study highlighted TMPRSS15 as the most likely effector gene at the ConLiGen lithium response locus. TMPRSS15 encodes enterokinase, a gastrointestinal enzyme responsible for converting trypsinogen into trypsin and thus aiding digestion. Convergent findings from gene-based lookups in human and mouse databases as well as co-expression network analyses of small intestinal RNA-seq data (GTEx) implicated TMPRSS15 in the regulation of intestinal nutrient absorption, including ions like sodium and potassium, which may extend to lithium.
LIMITATIONS
Although the findings from this study indicated that TMPRSS15 was the most likely effector gene at the ConLiGen lithium response locus, the evidence was circumstantial. Thus, the conclusions from this study need to be validated in appropriately designed wet-lab studies.
CONCLUSIONS
The findings from this study are consistent with a model whereby TMPRSS15 impacts the efficacy of lithium treatment in patients with bipolar disorder by modulating intestinal lithium absorption.
Topics: Bipolar Disorder; Humans; Intestinal Absorption; Computer Simulation; Serine Endopeptidases; Mice; Animals; Membrane Proteins; Lithium; Antimanic Agents; Genome-Wide Association Study; Lithium Compounds
PubMed: 38735581
DOI: 10.1016/j.jad.2024.05.050 -
Nutrients Apr 2024Vulvovaginal candidiasis (VVC) is the most common cause of vaginal discharge among women. The present study aimed to investigate the synergistic anticandidal effect of...
Vulvovaginal candidiasis (VVC) is the most common cause of vaginal discharge among women. The present study aimed to investigate the synergistic anticandidal effect of lactobacillus cultures supplemented with plant extracts. Among 600 isolates of lactic acid bacteria, 41 isolates exhibited inhibitory activity against ATCC10231. Six out of 41 cell-free supernatants demonstrated the most potent antibacterial and anticandidal activities. They also inhibited the clinical isolates of causing VVC and non-. The synergistic effect between 84/7 and 89/4 was demonstrated by the lowest fractional inhibitory concentration index (FICI = 0.5). The synbiotic culture of bacterial combination, cultured with Jerusalem artichoke () extract, also exhibited the strongest inhibition against the tested . Biofilm formation decreased after 12 h of incubation in the selected cell-free supernatants of this synbiotic culture. The anticandidal activity of crude extracts was lost after treatment with proteinase K and trypsin but not with heating conditions, suggesting that it may be a heat-stable substance. In conclusion, the combination of 84/7 and 89/4 with may be a promising candidate for inhibiting infection and biofilm formation, with the potential use as ingredients in vaginal biotherapeutic products.
Topics: Candida albicans; Plant Extracts; Female; Humans; Candidiasis, Vulvovaginal; Synbiotics; Vaginal Discharge; Biofilms; Lactobacillus; Limosilactobacillus reuteri; Lactobacillus crispatus; Antifungal Agents
PubMed: 38732618
DOI: 10.3390/nu16091372 -
Foods (Basel, Switzerland) May 2024Lima beans () and adzuki beans () are some of the most nutritious underutilized pulses that are significant in being used as basic ingredients for the preparation of...
Lima beans () and adzuki beans () are some of the most nutritious underutilized pulses that are significant in being used as basic ingredients for the preparation of various food products. The present study aimed to determine the impact of soaking and germination on nutritional and bioactive components, in vitro protein digestibility, reducing power, metal chelating capacity, antioxidant activity, and anti-nutritional components of lima and adzuki beans. The findings showed that during the germination treatment, the in vitro protein digestibility of lima and adzuki beans increased by 14.75 and 10.98%, respectively. There was an increase in the antioxidant activity of lima beans by 33.48% and adzuki beans by 71.14% after 72 h of germination, respectively. The reducing power assay of lima and adzuki beans indicated an increase of 49.52 and 36.42%, respectively, during germination. Similarly, the flavonoid and metal chelating activity increased in lima and adzuki beans after 72 h of germination. In contrast, the anti-nutrients, such as phytic acid, tannin content, and trypsin inhibitor activity, decreased significantly < 0.05 after 72 h of germination. These results are encouraging and allow for utilizing the flour obtained from the germinated beans in functional bakery products, which can contribute to eradicating protein deficiency among some population groups. At the same time, promoting soaking and germination of the beans as a way to enhance the nutritional quality and reduce anti-nutrients can contribute to the interest in these underutilized pulses. They could be seen as an additional tool to improve food security.
PubMed: 38731793
DOI: 10.3390/foods13091422 -
Foods (Basel, Switzerland) Apr 2024A novel fibrinolytic enzyme was produced by the liquid fermentation of . The enzyme was purified from the culture supernatant by hydrophobic interactions, gel...
A novel fibrinolytic enzyme was produced by the liquid fermentation of . The enzyme was purified from the culture supernatant by hydrophobic interactions, gel filtration, and ion exchange chromatographies. It was purified by 241.02-fold, with a specific activity of 3619 U/mg and a final yield of 10.02%. SDS-PAGE analysis confirmed the purity of the enzyme, showing a single band with a molecular weight of 19.5 kDa. The first nine amino acids of the N-terminal of the purified enzyme were A-T-Y-T-G-G-S-Q-T. The enzyme exhibited optimal activity at a temperature of 42 °C and pH 7.6. Its activity was significantly improved by Zn, K, Ca, Mn, and Mg while being inhibited by Fe, Fe, Al, and Ba. The activity of the enzyme was completely inhibited by ethylenediamine tetraacetic acid (EDTA), and it was also dose-dependently inhibited by phenylmethylsulfonyl fluoride (PMSF) and soy trypsin inhibitor (SBTI). However, inhibitors such as N-α-tosyl-L-phenylalanine chloromethyl ketone (TPCK), aprotinin, and pepstatin did not significantly affect its activity, suggesting that the enzyme was a serine-like metalloproteinase. The enzyme acted as both a plasmin-like fibrinolytic enzyme and a plasminogen activator, and it also exhibited the capability to hydrolyze fibrinogen and fibrin. In vitro, it demonstrated the ability to dissolve blood clots and exhibit anticoagulant properties. Furthermore, it was found that the enzyme prolonged activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT), and reduced the levels of fibrinogen (FIB) and prothrombin activity (PA). Based on these studies, the enzyme has great potential to be developed as a natural agent for the prevention and treatment of thrombotic diseases.
PubMed: 38731663
DOI: 10.3390/foods13091292 -
Animals : An Open Access Journal From... Apr 2024An 8-week feeding trial was performed to investigate the effects of dietary bile acids on growth, glucose metabolism, and intestinal health in spotted seabass () reared...
An 8-week feeding trial was performed to investigate the effects of dietary bile acids on growth, glucose metabolism, and intestinal health in spotted seabass () reared at high temperatures (33 °C). The fish (20.09 ± 1.12 g) were fed diets supplemented with bile acids: 0 (Con), 400 (BA400), 800 (BA800), and 1200 (BA1200) mg/kg, respectively. The results showed that the growth was promoted in fish at the BA800 treatment compared with the control ( < 0.05). Increased enzyme activities and transcripts of gluconeogenesis in the liver were observed, whereas decreased enzyme activities and transcripts of glycolysis, as well as glycogen content, were shown in the BA800 treatment ( < 0.05). The transcripts of bile acid receptors in the liver were up-regulated in the BA800 treatment ( < 0.05). A bile acid supplementation of 800 mg/kg improved the morphological structure in the intestine. Meanwhile, intestinal antioxidant physiology and activities of lipase and trypsin were enhanced in the BA800 treatment. The transcripts of genes and immunofluorescence intensity related to pro-inflammation cytokines (, , and ) were inhibited, while those of genes related to anti-inflammation ( and ) were induced in the BA800 treatment. Furthermore, transcripts of genes related to the NF-κB pathway in the intestine (, , , and ) were down-regulated in the BA800 treatment. This study demonstrates that a dietary bile acid supplementation of 800 mg/kg could promote growth, improve glucose metabolism in the liver, and enhance intestinal health by increasing digestive enzyme activity and antioxidant capacity and inhibiting inflammatory response in .
PubMed: 38731303
DOI: 10.3390/ani14091299 -
BMC Research Notes May 2024Bovine seminal plasma proteins perform several functions related to sperm function. Changes in the expression pattern or abundance of seminal proteins are related to...
OBJECTIVES
Bovine seminal plasma proteins perform several functions related to sperm function. Changes in the expression pattern or abundance of seminal proteins are related to changes in the fertilizing capacity of bulls. Considering the role of seminal plasma proteins in sperm function and animal reproduction, we investigated changes in the protein abundance profile in response to sperm morphological changes using a proteomic approach.
DATADESCRIPTION
In our present investigation, we employed liquid chromatography coupled with mass spectrometry to elucidate the proteomic composition of seminal plasma obtained from Nellore bulls exhibiting varying percentages of sperm abnormalities. Following semen collection, seminal plasma was promptly isolated from sperm, and proteins were subsequently precipitated, enzymatically digested using porcine trypsin, and subjected to analysis utilizing the Acquity nano UHPLC System in conjunction with a mass spectrometer. This dataset encompasses a total of 297 proteins, marking the inaugural instance in which a comparative profile of seminal plasma proteins in young Nellore bulls, categorized by their sperm abnormality percentages, has been delineated using LC-MS/MS. The comprehensive nature of this dataset contributes pivotal proteomic insights, representing a noteworthy advancement in our understanding of the reproductive biology of the Nellore breed.
Topics: Animals; Male; Cattle; Semen; Proteome; Spermatozoa; Tandem Mass Spectrometry; Proteomics; Seminal Plasma Proteins; Chromatography, Liquid
PubMed: 38730318
DOI: 10.1186/s13104-024-06796-7 -
American Journal of Veterinary Research May 2024Assess markers for pancreatic function and gastrointestinal malabsorption in African painted dogs (Lycaon pictus), including canine trypsin-like immunoreactivity (cTLI),...
Evaluation of trypsin-like immunoreactivity, pancreatic lipase immunoreactivity, cobalamin, and folate in zoo-housed African painted dogs (Lycaon pictus) at a North American zoological facility.
OBJECTIVE
Assess markers for pancreatic function and gastrointestinal malabsorption in African painted dogs (Lycaon pictus), including canine trypsin-like immunoreactivity (cTLI), canine pancreatic lipase immunoreactivity (cPLI), cobalamin, and folate at one North American facility.
ANIMALS
15 healthy African painted dogs held at one institution were sampled during routine health examinations.
METHODS
Blood was collected at routine health examinations, and serum was separated and stored until testing. Serum was analyzed for cTLI, cPLI, cobalamin, and folate. The results were evaluated for correlation to sex, age, and storage time of samples.
RESULTS
All individuals had cTLI and folate levels below normal reference ranges for domestic dogs (< 5.0 µg/L and < 7.7 µg/L, respectively). Cobalamin values were within or above reported domestic dog ranges, and cPLI values were within range as well. No analytes were significantly influenced by sex or time in storage, while cTLI was positively correlated with age.
CLINICAL RELEVANCE
cTLI and folate did not fall within normal domestic canid reference ranges in this population of healthy African painted dogs. Clinical interpretation of these values based on domestic canid recommendations would indicate clinical disease, which was not apparent in this population. Analytes for pancreatic function and malabsorption or gastrointestinal indicators, including cTLI, cPLI, and folate, in African painted dogs should be interpreted with caution when using domestic dog references ranges.
PubMed: 38729202
DOI: 10.2460/ajvr.24.02.0043 -
Journal of Proteomics Jun 2024This study explores the disulfide bridges present in the human milk proteome by a novel approach permitting both positional identification and relative quantification of...
This study explores the disulfide bridges present in the human milk proteome by a novel approach permitting both positional identification and relative quantification of the disulfide bridges. Human milk from six donors was subjected to trypsin digestion without reduction. The digested human milk proteins were analyzed by nanoLC-timsTOF Pro combined with data analysis using xiSEARCH. A total of 85 unique disulfide bridges were identified in 25 different human milk proteins. The total relative abundance of disulfide bridge-containing peptides constituted approximately 5% of the total amount of tryptic-peptides. Seven inter-molecular disulfide bridges were identified between either α-lactalbumin and lactotransferrin (5) or α-casein and κ-casein (2). All cysteines involved in the observed disulfide bridges of α-lactalbumin and lactotransferrin were mapped onto protein models using AlphaFold2 Multimer to estimate the length of the observed disulfide bridges. The lengths of the disulfide bridges of lactotransferrin indicate a potential for multi- or poly-merization of lactotransferrin. The high number of intramolecular lactotransferrin disulfide bridges identified, suggests that these are more heterogeneous than previously presumed. SIGNIFICANCE: Disulfide-bridges in the human milk proteome are an often overseen post-transaltional modification. Thus, mapping the disulfide-bridges, their positions and relative abundance, are valuable new knowledge needed for an improved understanding of human milk protein behaviour. Although glycosylation and phosphorylation have been described, even less information is available on the disulfide bridges and the disulfide-bridge derived protein complexes. This is important for future work in precision fermentation for recombinant production of human milk proteins, as this will highlight which disulfide-bridges are naturally occouring in human milk proteins. Further, this knowledge would be of value for the infant formula industry as it provides more information on how to humanize bovine-milk based infant formula. The novel method developed here can be broadly applied in other biological systems as the disulfid-brigdes are important for the structure and functionality of proteins.
Topics: Humans; Milk, Human; Disulfides; Proteomics; Proteome; Lactoferrin; Milk Proteins; Lactalbumin; Female
PubMed: 38723850
DOI: 10.1016/j.jprot.2024.105194 -
Journal of Veterinary Internal Medicine May 2024The purpose of this review was to analyze the scientific literature on exocrine pancreatic insufficiency (EPI) in dogs and cats and our own research on porcine model to... (Review)
Review
The purpose of this review was to analyze the scientific literature on exocrine pancreatic insufficiency (EPI) in dogs and cats and our own research on porcine model to compare animal- and microbial-derived enzymes in the treatment of animals with this disease. Clinical signs of EPI occur when more than 85% of the pancreatic parenchyma is non-functional. EPI can be a consequence of various diseases. The insufficient activity or deficiency of pancreatic enzymes leads to impaired digestion and absorption, and consequently, to malnutrition. The primary treatment for enzyme insufficiency is pancreatic enzyme replacement therapy (PERT). PERT in animals with EPI is a lifetime therapy. Most commercially available products are of animal origin (processed pancreata obtained from a slaughter house) and contain lipases, alpha-amylase, and proteases. Enzymes of microbial and plant origin seem to be a promising alternative to animal-derived enzymes, but to date there are no registered preparations containing all enzymes simultaneously for use in clinical practice to treat EPI. Results from some previous studies have highlighted the "extra-digestive" functions of pancreatic enzymes, as well as the actions of pancreatic-like microbial enzymes. For example, trypsin activates protease-activated receptor and provokes maturation of enterocytes and enterostatin inhibits fat absorption. It has been postulated that intrapancreatic amylase is the main component of the acini-islet-acinar axis-the reflex which down regulates insulin release, while gut and blood amylase exhibit anti-incretin actions "per se." Additionally, high but still physiological blood amylase activity coincide with physiological glucose homeostasis and a lack of obesity.
PubMed: 38721836
DOI: 10.1111/jvim.17096 -
Poultry Science Apr 2024This study aimed to evaluate the effect of low molecular weight Acanthopanax polysaccharides on simulated digestion, probiotics, and intestinal flora of broilers in...
Prebiotic characteristics of degraded polysaccharides from Acanthopanax senticosus polysaccharide on broilers gut microbiota based on in vitro digestion and fecal fermentation.
This study aimed to evaluate the effect of low molecular weight Acanthopanax polysaccharides on simulated digestion, probiotics, and intestinal flora of broilers in vitro. The experiments were carried out by HO-Vc degradation of Acanthopanax polysaccharides, in vitro simulated digestion to evaluate the digestive performance of polysaccharides with different molecular weights, in vitro probiotic evaluation of the probiotic effect of polysaccharides on lactobacilli and bifidobacteria, in vitro anaerobic fermentation and high-throughput sequencing of 16S rRNA genes to study the impact of Acanthopanax polysaccharides on the intestinal flora of broilers, and the effect of Acanthopanax polysaccharides on the short-chain fatty acids of intestines were determined by GC-MS method. The results showed that the molecular weight of Acanthopanax polysaccharide (ASPS) was 9,543 Da, and the molecular weights of polysaccharides ASPS-1 and ASPS-2 were reduced to 4,288 Da and 3,822 Da after degradation, and the particle sizes, PDIs, and viscosities were also significantly decreased. ASPS-1 has anti-digestive properties and better in vitro probiotic properties. The addition of ASPS-1 regulates the structure of intestinal microorganisms by regulating fecalibacterium to produce short-chain fatty acids, promoting the colonization of beneficial bacteria such as fecalibacterium, paraprevotella and diminishing the prevalence of detrimental bacteria such as Fusobacteria. Interestingly the ASPS-1 group found higher levels of Paraprevotella, which degraded trypsin in the gut, reducing inflammation, acted as a gut protector, and was influential in increasing the levels of acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and total SCFAs in the fermented feces. Therefore, the degraded ASPS-1 can better regulate the structure of intestinal flora and promote the production of SCFAs, creating possibilities for its use as a potential prebiotic, which is conducive to the intestinal health of poultry.
PubMed: 38713991
DOI: 10.1016/j.psj.2024.103807