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Zhongguo Dang Dai Er Ke Za Zhi =... May 2024Glyceryl phenylbutyrate (GPB) serves as a long-term management medication for Ornithine transcarbamylase deficiency (OTCD), effectively controlling hyperammonemia, but...
Glyceryl phenylbutyrate (GPB) serves as a long-term management medication for Ornithine transcarbamylase deficiency (OTCD), effectively controlling hyperammonemia, but there is a lack of experience in using this medicine in China. This article retrospectively analyzes the case of a child diagnosed with OTCD at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, including a review of related literature. After diagnosis, the patient was treated with GPB, followed by efficacy follow-up and pharmacological monitoring. The 6-year and 6-month-old male patient exhibited poor speech development, disobedience, temper tantrums, and aggressive behavior. Blood ammonia levels peaked at 327 μmol/L; urine organic acid analysis indicated elevated uracil levels; cranial MRI showed extensive abnormal signals in both cerebral hemispheres. Genetic testing revealed mutation in the gene (c.241T>C, p.S81P). Blood ammonia levels were approximately 43, 80, and 56 μmol/L at 1, 2, and 3 months after starting GPB treatment, respectively. During treatment, blood ammonia was well-controlled without drug-related adverse effects. The patient showed improvement in developmental delays, obedience, temperament, and absence of aggressive behavior.
Topics: Humans; Male; Ornithine Carbamoyltransferase Deficiency Disease; Phenylbutyrates; Child; Glycerol
PubMed: 38802913
DOI: 10.7499/j.issn.1008-8830.2310050 -
MedRxiv : the Preprint Server For... May 2024conducted a study within the Hispanic Community Health Study/Study of Latinos- Investigation of Neurocognitive Aging (HCHS/SOL-INCA) cohort to examine the association...
INTRODUCTION
conducted a study within the Hispanic Community Health Study/Study of Latinos- Investigation of Neurocognitive Aging (HCHS/SOL-INCA) cohort to examine the association between gut microbiome and cognitive function.
METHODS
We analyzed the fecal metagenomes of 2,471 HCHS/SOL-INCA participants to, cross-sectionally, identify microbial taxonomic and functional features associated with global cognitive function. Omnibus (PERMANOVA) and feature-wise analyses (MaAsLin2) were conducted to identify microbiome-cognition associations, and specific microbial species and pathways (Kyoto Encyclopedia of Genes and Genomes (KEGG modules) associated with cognition.
RESULTS
species( and ), were associated with better cognition. Several KEGG modules, most strongly Ornithine, Serine biosynthesis and Urea Cycle, were associated with worse cognition.
DISCUSSION
In a large Hispanic/Latino cohort, we identified several microbial taxa and KEGG pathways associated with cognition.
PubMed: 38798527
DOI: 10.1101/2024.05.17.24307533 -
Plants (Basel, Switzerland) May 2024Hairgrass (), a widely distributed grass species considered promising in the ecological restoration of degraded grassland in the Qinghai-Xizang Plateau, is likely to be...
Hairgrass (), a widely distributed grass species considered promising in the ecological restoration of degraded grassland in the Qinghai-Xizang Plateau, is likely to be subjected to frequent drought and waterlogging stress due to ongoing climate change, further aggravating the degradation of grassland in this region. However, whether it would acclimate to water stresses resulting from extreme climates remains unknown. Proline accumulation is a crucial metabolic response of plants to challenging environmental conditions. This study aims to investigate the changes in proline accumulation and key enzymes in hairgrass shoot and root tissues in response to distinct climate extremes including moderate drought, moderate waterlogging, and dry-wet variations over 28 days using a completely randomized block design. The proline accumulation, contribution of the glutamate and ornithine pathways, and key enzyme activities related to proline metabolism in shoot and root tissues were examined. The results showed that water stress led to proline accumulation in both shoot and root tissues of hairgrass, highlighting the importance of this osmoprotectant in mitigating the effects of environmental challenges. The differential accumulation of proline in shoots compared to roots suggests a strategic allocation of resources by the plant to cope with osmotic stress. Enzymatic activities related to proline metabolism, such as Δ-pyrroline-5-carboxylate synthetase, ornithine aminotransferase, Δ-pyrroline-5-carboxylate reductase, Δ-pyrroline-5-carboxylate dehydrogenase, and proline dehydrogenase, further emphasize the dynamic regulation of proline levels in hairgrass under water stress conditions. These findings support the potential for enhancing the stress resistance of hairgrass through the genetic manipulation of proline biosynthesis and catabolism pathways.
PubMed: 38794479
DOI: 10.3390/plants13101408 -
Microorganisms May 2024B13, selected from fermentation chili, has been proven to promote animal growth by previous studies, but it belongs to opportunistic pathogens, so a comprehensive...
B13, selected from fermentation chili, has been proven to promote animal growth by previous studies, but it belongs to opportunistic pathogens, so a comprehensive evaluation of its probiotic properties and safety is necessary. In this study, the probiotic properties and safety of B13 were evaluated at the genetic and phenotype levels in vitro and then confirmed in vivo. The genome of B13 contains one chromosome and two plasmids. The average nucleotide identity indicated that B13 was most closely related to the fermentation-plant-derived strain. The strain does not carry the major virulence genes of the clinical strains but contains , , genes. The strain had a higher tolerance to acid at pH 3.0, 4.0, and 0.3% bile salt and a 32.83% free radical DPPH clearance rate. It can adhere to Caco-2 cells and reduce the adhesion of to Caco-2 cells. The safety assessment revealed that the strain showed no hemolysis and did not exhibit gelatinase, ornithine decarboxylase, lysine decarboxylase, or tryptophanase activity. It was sensitive to twelve antibiotics but was resistant to erythromycin, rifampicin, tetracycline, doxycycline, and minocycline. Experiments in vivo have shown that B13 can be located in the ileum and colon and has no adverse effects on experiment animals. After 28 days of feeding, B13 did not remarkable change the α-diversity of the gut flora or increase the virulence genes. Our study demonstrated that B13 may be used as a probiotic candidate.
PubMed: 38792822
DOI: 10.3390/microorganisms12050994 -
Scientific Reports May 2024Hepatic encephalopathy (HE), a morbid ordeal affecting chronic liver disease patients always insists for the search of a rational, superior & infallible agent beyond the... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Hepatic encephalopathy (HE), a morbid ordeal affecting chronic liver disease patients always insists for the search of a rational, superior & infallible agent beyond the time-proven standards i.e., Lactulose & Rifaximin. In this RCT, we compared the efficacy of intravenous (IV) L-ornithine-L-aspartate(LOLA) versus Oral LOLA in patients with chronic liver disease(CLD) enduring overt Hepatic Encephalopathy(OHE). 40 CLD patients with OHE were randomly assigned IV or oral LOLA in a 1:1 ratio. Patients were graded for HE and monitored for serum ammonia levels from day 1 to day 5. The aim was to compare IV versus oral LOLA efficacy in HE grades improvement and its correlation with ammonia levels. The study was registered with clinical trials registry-India, CTRI/2020/12/029943. Baseline characteristics of patients in both groups were similar. The mean difference in ammonia levels from day 1 to day 5 was 55.4 ± 32.58 µmol/L in the IV LOLA group and 60.75 ± 13.82 µmol/L in the oral LOLA group (p = 0.511). Significant reductions in ammonia levels were observed from day 1 to day 5 within each group (p < 0.001). HE grade & ammonia correlated positively in both groups. LOLA, regardless of administration route, has demonstrated efficacy in OHE.
Topics: Humans; Hepatic Encephalopathy; Male; Female; Middle Aged; Administration, Oral; Dipeptides; Ammonia; Administration, Intravenous; Adult; Treatment Outcome; Aged
PubMed: 38789596
DOI: 10.1038/s41598-024-62293-8 -
Journal of Inorganic Biochemistry May 2024Nine new organotin (IV) derivatives from L-amino acids (l-lysine, L-ornithine, L-glutamic acid, and L-aspartic acid) were synthesized by one-pot ultrasound-assisted...
Nine new organotin (IV) derivatives from L-amino acids (l-lysine, L-ornithine, L-glutamic acid, and L-aspartic acid) were synthesized by one-pot ultrasound-assisted methodology. All compounds were characterized by ATR-FTIR (Attenuated Total Reflectance-Fourier Transform Infrared), LRMS (Low-Resolution Mass Spectrometry), and solution NMR (H, C, Sn Nuclear Magnetic Resonance) spectroscopies. Complexes BuSn(Lys) (1), PhSn(Lys) (2), BuSn(Orn) (3), and PhSn (Glu-OMe) (6a) were crystallized, and the structures were established by single-crystal X-ray diffraction analysis. Diffraction results evidenced that complexes 1 to 3 were five-coordinated mononuclear species while the phenyl substituted derivative PhSn (Glu-OMe) (6a) forms a polymeric network via Sn-O-Sn bridging whereby the tin atom is six-coordinated. In turn, Sn NMR results revealed that all tin complexes exist as mononuclear penta-coordinated species in solution. The tin derivatives were screened for ADME (Adsorption, Distribution, Metabolism, and Excretion) properties via the freely available tools SWISS ADME, and the results were analyzed hereafter. The antiproliferative activity of the complexes was tested against three human cancer cell lines: colorectal adenocarcinoma HT-29, breast adenocarcinoma MDA-MB-231, and chondrosarcoma SW-1353 using a non-tumoral cell line of human osteoblast as control, demonstrating selective inhibitory activities against cancer cells. Hence, these compounds could be a promising alternative to classical chemotherapy agents.
PubMed: 38772186
DOI: 10.1016/j.jinorgbio.2024.112602 -
International Journal of Ophthalmology 2024To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy (DR) and provide a novel strategy to elucidate the...
AIM
To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy (DR) and provide a novel strategy to elucidate the pathological mechanism of DR.
METHODS
The fecal samples from 32 type 2 diabetes patients with proliferative retinopathy (PDR), 23 with non-proliferative retinopathy (NPDR), 27 without retinopathy (DM), and 29 from the sex-, age- and BMI- matched healthy controls (29 HC) were analyzed by 16S rDNA gene sequencing. Sixty fecal samples from PDR, DM, and HC groups were assayed by untargeted metabolomics. Fecal metabolites were measured using liquid chromatography-mass spectrometry (LC-MS) analysis. Associations between gut microbiota and fecal metabolites were analyzed.
RESULTS
A cluster of 2 microbiome and 12 metabolites accompanied with the severity of DR, and the close correlation of the disease progression with PDR-related microbiome and metabolites were found. To be specific, the structure of gut microbiota differed in four groups. Diversity and richness of gut microbiota were significantly lower in PDR and NPDR groups, than those in DM and HC groups. A cluster of microbiome enriched in PDR group, including , , , , was observed. Functional analysis showed that the glucose and nicotinate degradations were significantly higher in PDR group than those in HC group. Arginine, serine, ornithine, and arachidonic acid were significantly enriched in PDR group, while proline was enriched in HC group. Functional analysis illustrated that arginine biosynthesis, lysine degradation, histidine catabolism, central carbon catabolism in cancer, D-arginine and D-ornithine catabolism were elevated in PDR group. Correlation analysis revealed that and were positively associated with L-arginine, ornithine levels in fecal samples.
CONCLUSION
This study elaborates the different microbiota structure in the gut from four groups. The relative abundance of and are associated with the severity of DR. Amino acid and fatty acid catabolism is especially disordered in PDR group. This may help provide a novel diagnostic parameter for DR, especially PDR.
PubMed: 38766339
DOI: 10.18240/ijo.2024.05.13 -
BMC Microbiology May 2024This study aimed to discuss the distinctive features of the intestinal microbiota in neonates with hyperbilirubinemia and to comprehensively analyse the composition of...
OBJECTIVE
This study aimed to discuss the distinctive features of the intestinal microbiota in neonates with hyperbilirubinemia and to comprehensively analyse the composition of the intestinal microbiota as well as the levels of free amino acids and acylcarnitines in the peripheral blood of neonates experiencing hyperbilirubinemia.
RESULTS
At the phylum level, Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, and Chloroflexi were the five predominant microbial groups identified in both the hyperbilirubinemia and control groups. Alpha diversity analysis, encompassing seven indices, showed no statistically significant differences between the two groups. However, Beta diversity analysis revealed a significant difference in intestinal microbiota structure between the groups. Linear discriminant analysis effect size (LEfSe) indicated a significant reduction in the abundance of Gammaproteobacteria and Enterobacteriaceae within the hyperbilirubinemia group compared to that in the control group. The heatmap revealed that the control group exhibited increased abundances of Escherichia and Bifidobacterium, while the hyperbilirubinemia group exhibited increased levels of Enterococcus and Streptococcus. Regarding blood amino acids and acylcarnitines, there were greater concentrations of citrulline (Cit), arginine (Arg), ornithine (Orn), and valine (Val) in the hyperbilirubinemia group than in the control group. The hyperbilirubinemia group also exhibited significant increases in medium-chain fatty acids (C6, C8), long-chain fatty acids (C18), and free carnitine (C0).
CONCLUSION
By comparing neonates with hyperbilirubinemia to those without, a significant disparity in the community structure of the intestinal microbiota was observed. The intestinal microbiota plays a crucial role in the bilirubin metabolism process. The intestinal microbiota of neonates with hyperbilirubinemia exhibited a certain degree of dysbiosis. The abundances of Bacteroides and Bifidobacterium were negatively correlated with the bilirubin concentration. Therefore, the fact that neonates with hyperbilirubinemia exhibit some variations in blood amino acid and acylcarnitine levels may provide, to a certain degree, a theoretical basis for clinical treatment and diagnosis.
Topics: Humans; Carnitine; Gastrointestinal Microbiome; Amino Acids; Infant, Newborn; Male; Female; Bacteria; RNA, Ribosomal, 16S
PubMed: 38760685
DOI: 10.1186/s12866-024-03328-y -
Frontiers in Immunology 2024It is essential to understand the interactions and relationships between () and macrophages during the infection in order to design host-directed,...
It is essential to understand the interactions and relationships between () and macrophages during the infection in order to design host-directed, immunomodulation-dependent therapeutics to control . We had reported previously that ornithine acetyltransferase (MtArgJ), a crucial enzyme of the arginine biosynthesis pathway of , is allosterically inhibited by pranlukast (PRK), which significantly reduces bacterial growth. The present investigation is centered on the immunomodulation in the host by PRK particularly the activation of the host's immune response to counteract bacterial survival and pathogenicity. Here, we show that PRK decreased the bacterial burden in the lungs by upregulating the population of pro-inflammatory interstitial macrophages (IMs) and reducing the population of susceptible alveolar macrophages (AMs), dendritic cells (DCs), and monocytes (MO). Additionally, we deduce that PRK causes the host macrophages to change their metabolic pathway from fatty acid metabolism to glycolytic metabolism around the log phage of bacterial multiplication. Further, we report that PRK reduced tissue injury by downregulating the Ly6C-positive population of monocytes. Interestingly, PRK treatment improved tissue repair and inflammation resolution by increasing the populations of arginase 1 (Arg-1) and Ym1+Ym2 (chitinase 3-like 3) positive macrophages. In summary, our study found that PRK is useful not only for reducing the tubercular burden but also for promoting the healing of the diseased tissue.
Topics: Animals; Mycobacterium tuberculosis; Mice; Disease Models, Animal; Chromones; Antitubercular Agents; Tuberculosis; Macrophages; Mice, Inbred C57BL; Female; Tuberculosis, Pulmonary; Lung
PubMed: 38756781
DOI: 10.3389/fimmu.2024.1347045 -
Frontiers in Immunology 2024The objective of this study was to investigate the impact of electro-acupuncture (EA) on sepsis-related intestinal injury and its relationship with macrophage...
OBJECTIVE
The objective of this study was to investigate the impact of electro-acupuncture (EA) on sepsis-related intestinal injury and its relationship with macrophage polarization.
METHODS
A sepsis model was established using cecal ligation and puncture (CLP) to assess the effectiveness of EA. The extent of pathological injury was evaluated using Chiu's score, the expression of ZO-1 and Ocludin, and the impact on macrophage polarization was examined through flow cytometry and immunofluorescence staining. The expression of spermidine, one type of polyamine, and ornithine decarboxylase (ODC) was measured using ELISA and PCR. Once the efficacy was determined, a polyamine depletion model was created, and the role of polyamines was reassessed by evaluating efficacy and observing macrophage polarization.
RESULTS
EA treatment reduced the Chiu's score and increased the expression of ZO-1 and Ocludin in the intestinal tissue of septic mice. It inhibited the secretion of IL-1β and TNF-α, promoted the polarization of M2-type macrophages, increased the secretion of IL-10, and upregulated the expression of Arg-1, spermidine, and ODC. However, after depleting polyamines, the beneficial effects of EA on alleviating intestinal tissue damage and modulating macrophage polarization disappeared.
CONCLUSION
The mechanism underlying the alleviation of intestinal injury associated with CLP-induced sepsis by EA involves with the promotion of M2-type macrophage polarization mediated by spermidine expression.
Topics: Animals; Sepsis; Mice; Macrophages; Electroacupuncture; Polyamines; Male; Disease Models, Animal; Macrophage Activation; Intestines; Mice, Inbred C57BL; Cytokines
PubMed: 38715602
DOI: 10.3389/fimmu.2024.1373876