PubMed

Sci Total Environ. 2022 Dec 29:161261. doi: 10.1016/j.scitotenv.2022.161261. Online ahead of print.ABSTRACTPerfluorobutanesulfonate (PFBS), an alternative to perfluorooctanesulfonate (PFOS), has raised many health concerns. However, PFBS toxicity in the mammalian gut remains unclear. C57BL/6 mice were exposed to 10 μg/L and 500 μg/L PFBS or 500 μg/L PFOS in their water supply for 28 days. PFBS toxicity in the ileum and colon was explored and compared to that of PFOS. Biochemical analysis showed that and tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels increased in the ileum exposed to 10 μg/L PFBS, whereas no significant changes were observed in those levels in the colon. Catalase (CAT) activity, malondialdehyde (MDA), TNF-α, and IL-1β levels increased and glutathione (GSH) levels decreased in the ileum of the 500 μg/L-PFBS group, whereas only MDA levels increased in the colon of the 500 μg/L-PFBS group. The results showed that more severe damage occurred in the ileum than in the colon after PFBS exposure, and these align with the 500 μg/L-PFOS group exposure as well. Furthermore, metabolomic analysis revealed glutathione metabolism as a vital factor in inducing PFBS and PFOS toxicities in the ileum. Steroid hormone and amino acid metabolisms were other important factors involved in PFBS and PFOS toxicities, respectively. In the colon, GSH, pyrimidine, and glucose (especially galactose) metabolism was the main contributor to PFBS toxicity, and sulfur amino acid metabolism was the main pathway for PFOS toxicity. This study provides more evidence of the health hazards due to low-dose PFBS exposure in the mammalian gut.PMID:36587682 | DOI:10.1016/j.scitotenv.2022.161261

J Hazard Mater. 2022 Dec 23;446:130659. doi: 10.1016/j.jhazmat.2022.130659. Online ahead of print.ABSTRACTThis study aimed to investigate the relationship among chronic exposure to a low concentration of organochlorine pesticides (OCPs), high-fat diet (HFD)-induced obesity, and caloric restriction in type 2 diabetes (T2D). Thus, female zebrafish were divided into four groups and treated for 12 weeks as follows: (i) negative control, (ii) HFD (obesity) control, (iii) obesity + a mixture of OCPs (OP), and (iv) obesity + a mixture of OCPs + caloric restriction (OPR). We then assessed T2D-related effects via hematological analysis, histopathology, mitochondrial evaluation, and multiomics analyses. The OP group showed a significant increase in glucose levels, whereas the OPR group maintained glucose at nonsignificant levels. Multiomics analyses revealed that the exacerbated metabolic effects in the OP group were associated with molecular alterations in oxidative stress, inflammation, nucleotide metabolism, and glucose/lipid homeostasis. These alterations were histologically verified by the increased numbers of hypertrophic adipocytes and inflammatory cells observed. Caloric restriction activated pathways related to antioxidant response, mitochondrial fatty acid oxidation, and energy metabolism in zebrafish, leading to preserved glucose homeostasis. In conclusion, this study identified molecular mechanisms underlying the synergistic effect of concurrent exposure to a mixture of OCPs and HFD as well as shed light on the beneficial effect of regular caloric restriction in T2D development.PMID:36587596 | DOI:10.1016/j.jhazmat.2022.130659

Nutr Res. 2022 Dec 8;109:58-70. doi: 10.1016/j.nutres.2022.12.002. Online ahead of print.ABSTRACTIntake biomarkers of cranberry juice in women can assess consumption in clinical trials. Discriminant biomarkers in urine may explain urinary tract infection (UTI) preventive activities. We hypothesized that validated and annotated discriminant metabolites in human urine could be used as intake biomarkers in building predictive multivariate models to classify cranberry consumers. Urine samples were collected from 16 healthy women aged 18 to 29 years at baseline and after 3- and 21-day consumption of cranberry or placebo juice in a double-blind, crossover study. Urine metabolomes were analyzed using ultra high-performance liquid chromatography coupled with Orbitrap mass spectrometry. Paired and unpaired multivariate analyses were used to annotate or identify discriminant metabolic features after cranberry consumption. Twenty-six discriminant metabolic features (paired analysis) and 27 (unpaired analysis) after cranberry consumption in an open-label intervention were rediscovered in the blinded study. These metabolites included exogenous (quinic acid) and endogenous ones (hippuric acid). The paired analysis showed better model fitting with partial least-square discriminant analysis models built on all metabolites than the unpaired analysis. Predictive models built on shared metabolites by the unpaired analysis were able to classify cranberry juice consumers with 84.4% to 100% correction rates, overall better than the paired analysis (50%-100%). The double-blind study validated discriminant metabolites from a previous open-label study. These urinary metabolites may be associated with the ability of cranberries to prevent UTIs and serve as potential cranberry intake biomarkers. It reveals the importance of selecting the right predictive models to classify cranberry consumers with higher than 95% correction rates.PMID:36587538 | DOI:10.1016/j.nutres.2022.12.002

Mar Pollut Bull. 2022 Dec 30;187:114534. doi: 10.1016/j.marpolbul.2022.114534. Online ahead of print.ABSTRACTAnalyses of the transcriptome and metabolome were conducted to clarify alterations of key genes and metabolites in pearl oysters following exposure to short-term hypoxic treatment. We totally detected 209 DEGs between the control and hypoxia groups. Enrichment analysis indicated the enrichment of GO terms including "oxidation-reduction process", "ECM organization", "chaperone cofactor-dependent protein refolding", and "ECM-receptor interaction" KEGG pathway by the DEGs. In addition, between the two groups, a total of 28 SDMs were identified, which were implicated in 13 metabolic pathways, such as "phenylalanine metabolism", "D-amino acid metabolism", and "aminoacyl-tRNA biosynthesis". Results suggest that pearl oysters are exposed to oxidative stress and apoptosis under short-term hypoxia. Also, pearl oysters might adapt to short-term hypoxic treatment by increasing antioxidant activity, modulating immune and biomineralization activities, maintaining protein homeostasis, and reorganizing the cytoskeleton. The results of our study help unveil the mechanisms by which pearl oysters respond adaptively to short-term hypoxia.PMID:36587532 | DOI:10.1016/j.marpolbul.2022.114534

Mol Oncol. 2023 Jan 1. doi: 10.1002/1878-0261.13372. Online ahead of print.ABSTRACTPreclinical studies have proven that nanosecond pulsed electric field (nsPEF) ablation can be a safe and effective treatment for humans with unresectable liver cancer that are ineligible for thermal ablation. The concomitant activation of anti-tumor immunity by nsPEF can also potentially prevent tumor recurrence. However, whether nsPEF exhibits similar efficacy in a clinical setting remains to be investigated. A prospective clinical trial (clinicaltrials.gov identifier: NCT04039747) was conducted to evaluate the safety and efficacy of ultrasound (US)-guided nsPEF ablation in 15 patients with unresectable liver cancer that were ineligible for thermal ablation. We found that nsPEF ablation was safe and produced a 12-month recurrence-free survival (RFS) and local RFS of 60% (9/15) and 86.7% (13/15), respectively, in the enrolled patients. Integrative proteomic and metabolomic analysis showed that sphingolipid metabolism was the most significantly enriched pathway in patient sera after nsPEF without recurrence within 8 months. A similar upregulation of sphingolipid metabolism was observed in the intratumoral mononuclear phagocytes (MNPs), rather than other immune and nonimmune cells, of an nsPEF-treated mouse model. We then demonstrated that lymphocyte antigen 6 complex, locus C2-positive (Ly6c2+ ) monocytes first differentiated into Ly6c2+ monocyte-derived macrophages (MDMs) with an increase in sphingolipid metabolic activity, and subsequently into Ly6c2+ dendritic cells (DCs). Ly6c2+ DCs communicated with CD8+ T cells and increased the proportions of IFN-γ+ CD8+ memory T cells after nsPEF, and this finding was subsequently confirmed by depletion of liver Ly6c2+ MNPs. In conclusion, nsPEF was a safe and effective treatment for liver cancer. The alteration of sphingolipid metabolism induced by nsPEF was associated with the differentiation of Ly6c2+ MNPs, and subsequently induced the formation of memory CD8+ T cells with potent anti-tumor effect.PMID:36587393 | DOI:10.1002/1878-0261.13372

J Dairy Sci. 2022 Dec 29:S0022-0302(22)00761-5. doi: 10.3168/jds.2022-22654. Online ahead of print.ABSTRACTBrown goat milk products have gained popularity for their unique taste and flavor. The emergence of chain-reversal phenomenon makes the design and development of goat milk products gradually tend to a consumer-oriented model. However, the precise mechanism of how browning and fermentation process causes characteristics is not clear. In an effort to understand how the treatments potentially lead to certain metabolite profile changes in goat milk, comprehensive, quantitative metabolomics and peptidomics analysis of goat milk samples after browning and fermentation were undertaken. An intelligent hybrid z-score standardization-principal components algorithm-multimodal denoizing autoencoder was used for feature fusion and hidden layer fusion in high-dimensional variable space. The fermentation process significantly improved the flavor of brown goat yogurt through the tricarboxylic acid-urea-glycolysis composite pathway. Bitter peptides HPFLEWAR, PPGLPDKY, and PPPPPKK have strong interactions with both putative dipeptidyl peptidase IV and angiotensin-converting enzyme, proving that brown goat yogurt can be considered as effective provider of potential putative dipeptidyl peptidase IV and angiotensin-converting enzyme inhibitors. The level of health-promoting bioactive components and sensory contributed to consumer selection. The proposed multimodal data integrative analysis platform was applicable to explain the effect of the dynamic changes of metabolites and peptides on consumer preferences.PMID:36586795 | DOI:10.3168/jds.2022-22654

Neuroimage. 2022 Dec 28:119843. doi: 10.1016/j.neuroimage.2022.119843. Online ahead of print.ABSTRACTMediation analysis is used to investigate the role of intermediate variables (mediators) that lie in the path between an exposure and outcome variable. While significant research has focused on developing methods for assessing the influence of mediators on the exposure-outcome relationship, current approaches do not easily extend to settings where the mediator is high-dimensional (e.g., neuroimaging, genomics, and metabolomics). Here we introduce a novel machine learning based method for identifying high-dimensional mediators. The proposed algorithm is agnostic to the machine learning model used, providing significant flexibility in the types of situations it can be applied. We illustrate the proposed methodology using data from two functional Magnetic Resonance Imaging studies. In both, our multivariate mediation model links exposure variables, high dimensional brain measures and behavioral outcomes into a single unified model. Using the proposed approach, we identify brain-based measures that simultaneously encode the exposure variable and correlate with the behavioral outcome.PMID:36586543 | DOI:10.1016/j.neuroimage.2022.119843

J Ethnopharmacol. 2022 Dec 28:116013. doi: 10.1016/j.jep.2022.116013. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Cough variant asthma (CVA) is a chronic inflammatory disease characterized by cough as the main symptom. Suhuang antitussive capsule (Suhuang), one of traditional Chinese patent medicines, mainly treats CVA clinically. Previous studies have shown that Suhuang significantly improved CVA, post-infectious cough (PIC), sputum obstruction and airway remodeling. However, the effect of Suhuang on ovalbumin-induced (OVA-induced) metabolic abnormalities in CVA is unknown.AIM OF THE STUDY: This study aimed to identify potential metabolites associated with efficacy of Suhuang in the treatment of CVA, and determined how Suhuang regulates metabolites, and differential metabolites reduce inflammation and oxidative stress.MATERIALS AND METHODS: Rats were given 1 mg OVA/100 mg aluminum hydroxide in the 1st and 7th days by intraperitoneal injection and challenged by atomizing inhalation of 1% OVA saline solution after two weeks to establish the CVA model. Rats were intragastrically (i.g.) administrated with Suhuang at 1.4 g/kg and β-hydroxybutyric acid (β-HB) were given with different concentrations (87.5 and 175 mg/kg/day) by intraperitoneal injection for 2 weeks. After 26 days, GC-MS-based metabolomic approach was applied to observe metabolic changes and search differential metabolites. The number of coughs, coughs latencies, enzyme-linked immunosorbent assay (ELISA), histological analysis and quantitative-polymerase chain reaction (Q-PCR) were used to investigate the effects of Suhuang. Then β-HB on CVA rats, NLRP3 inflammasome and GSK3β/AMPK/Nrf2 signalling pathway were detected by western blotting.RESULTS: The results showed that Suhuang treatment significantly enhanced the serum level of β-HB. Interestingly, exposure to exogenous β-HB was also protective against OVA-induced CVA. β-HB significantly reduced the number of coughs and lengthened coughs latencies, improved lung injury, reduced the secretion of various cytokines, and directly inhibited the NLRP3 inflammasome. In addition, β-HB increased the nuclear accumulation of Nrf2 by activating the GSK3β/AMPK signaling axis, and then inactivating the NF-κB signaling pathway, effectively protecting OVA-induced CVA from oxidative stress and inflammation.CONCLUSIONS: The results of this study shows that β-HB can reduce inflammation and oxidative stress, the increased production of β-HB in serum might be the crucial factor for Suhuang to exert its effect in the treatment of CVA.PMID:36586526 | DOI:10.1016/j.jep.2022.116013

Food Chem. 2022 Dec 28;409:135342. doi: 10.1016/j.foodchem.2022.135342. Online ahead of print.ABSTRACTAs a common food processing technology, microbial fermentation is becoming increasingly popular to promote the bioactivity of materials. This study aims to enhance rape bee pollen bioactivity through fermentation and trace the potential components associated with its bioactivity. The antioxidant and anti-inflammatory activities of unfermented bee pollen and fermented bee pollen were evaluated, and their correlation with differential metabolites was analyzed. The results indicated that fermentation significantly (p < 0.05) improved the antioxidant (>2.3-fold) and anti-inflammatory (>1.36-fold) activities of bee pollen, and increased the contents of total phenolics and flavonoids by 1.99 and 1.53 folds. Moreover, the correlation analysis results indicated that 15 components, including three phenolamides, one flavonoid aglycone, seven fatty acids, three amino acids and one ketone compound, were positively correlated with bee pollen antioxidant and anti-inflammatory activities. These results suggest that fermentation is a promising approach to increase the bioactivity of bee pollen.PMID:36586262 | DOI:10.1016/j.foodchem.2022.135342

Curr Opin Chem Biol. 2022 Dec 29;72:102256. doi: 10.1016/j.cbpa.2022.102256. Online ahead of print.ABSTRACTDespite being a relatively new addition to the Omics' landscape, lipidomics is increasingly being recognized as an important tool for the identification of druggable targets and biochemical markers. In this review we present recent advances of lipid analysis in drug discovery and development. We cover current state of the art technologies which are constantly evolving to meet demands in terms of sensitivity and selectivity. A careful selection of important examples is then provided, illustrating the versatility of lipidomics analysis in the drug discovery and development process. Integration of lipidomics with other omics', stem-cell technologies, and metabolic flux analysis will open new avenues for deciphering pathophysiological mechanisms and the discovery of novel targets and biomarkers.PMID:36586190 | DOI:10.1016/j.cbpa.2022.102256

BMC Cancer. 2022 Dec 30;22(1):1366. doi: 10.1186/s12885-022-10457-y.ABSTRACTBACKGROUND: The gut microbiome plays an important role in immune modulation. Specifically, presence or absence of certain gut bacterial taxa has been associated with better antitumor immune responses. Furthermore, in trials using fecal microbiota transplantation (FMT) to treat melanoma patients unresponsive to immune checkpoint inhibitors (ICI), complete responses (CR), partial responses (PR), and durable stable disease (SD) have been observed. However, the underlying mechanism determining which patients will or will not respond and what the optimal FMT composition is, has not been fully elucidated, and a discrepancy in microbial taxa associated with clinical response has been observed between studies. Furthermore, it is unknown whether a change in the microbiome itself, irrespective of its origin, or FMT from ICI responding donors, is required for reversion of ICI-unresponsiveness. To address this, we will transfer microbiota of either ICI responder or nonresponder metastatic melanoma patients via FMT.METHODS: In this randomized, double-blinded phase Ib/IIa trial, 24 anti-PD1-refractory patients with advanced stage cutaneous melanoma will receive an FMT from either an ICI responding or nonresponding donor, while continuing anti-PD-1 treatment. Donors will be selected from patients with metastatic melanoma treated with anti-PD-1 therapy. Two patients with a good response (≥ 30% decrease according to RECIST 1.1 within the past 24 months) and two patients with progression (≥ 20% increase according to RECIST 1.1 within the past 3 months) will be selected as ICI responding or nonresponding donors, respectively. The primary endpoint is clinical benefit (SD, PR or CR) at 12 weeks, confirmed on a CT scan at 16 weeks. The secondary endpoint is safety, defined as the occurrence of grade ≥ 3 toxicity. Exploratory endpoints are progression-free survival and changes in the gut microbiome, metabolome, and immune cells.DISCUSSION: Transplanting fecal microbiota to restore the patients' perturbed microbiome has proven successful in several indications. However, less is known about the potential role of FMT to improve antitumor immune response. In this trial, we aim to investigate whether administration of FMT can reverse resistance to anti-PD-1 treatment in patients with advanced stage melanoma, and whether the ICI-responsiveness of the feces donor is associated with its effectiveness.TRIAL REGISTRATION: ClinicalTrials.gov: NCT05251389 (registered 22-Feb-2022). Protocol V4.0 (08-02-2022).PMID:36585700 | DOI:10.1186/s12885-022-10457-y

Lipids Health Dis. 2022 Dec 31;21(1):151. doi: 10.1186/s12944-022-01765-0.ABSTRACTBACKGROUND: Both hyperuricaemia and hyperlipidaemia are common metabolic diseases that are closely related to each other, and both are independent risk factors for the development of a variety of diseases. HUA combined with hyperlipidaemia increases the risk of nonalcoholic fatty liver disease and coronary heart disease. This study aimed to investigate the relationship between HUA and hyperlipidaemia and study the metabolic pathway changes in patients with HUA associated with hyperlipidaemia using metabolomics.METHODS: This was a case‒control study. The prevalence of hyperlipidaemia in HUA patients in the physical examination population of Tianjin Union Medical Centre in 2018 was investigated. Metabolomics analysis was performed on 308 HUA patients and 100 normal controls using Orbitrap mass spectrometry. A further metabolomics study of 30 asymptomatic HUA patients, 30 HUA patients with hyperlipidaemia, and 30 age-and sex-matched healthy controls was conducted. Differential metabolites were obtained from the three groups by orthogonal partial least-squares discrimination analysis, and relevant metabolic pathways changes were analysed using MetaboAnalyst 5.0 software.RESULTS: The prevalence of hyperlipidaemia in HUA patients was 69.3%. Metabolomic analysis found that compared with the control group, 33 differential metabolites, including arachidonic acid, alanine, aspartate, phenylalanine and tyrosine, were identified in asymptomatic HUA patients. Pathway analysis showed that these changes were mainly related to 3 metabolic pathways, including the alanine, aspartate and glutamate metabolism pathway. Thirty-eight differential metabolites, including linoleic acid, serine, glutamate, and tyrosine, were identified in HUA patients with hyperlipidaemia. Pathway analysis showed that they were mainly related to 7 metabolic pathways, including the linoleic acid metabolism pathway, phenylalanine, tyrosine and tryptophan biosynthesis pathway, and glycine, serine and threonine metabolism pathway.CONCLUSIONS: Compared to the general population, the HUA population had a higher incidence of hyperlipidaemia. HUA can cause hyperlipidaemia. by affecting the metabolic pathways of linoleic acid metabolism and alanine, aspartate and glutamate metabolism. Fatty liver is closely associated with changes in the biosynthesis pathway of pahenylalanine, tyrosine, and tryptophan in HUA patients with hyperlipidaemia. Changes in the glycine, serine and threonine metabolism pathway in HUA patients with hyperlipidaemia may lead to chronic kidney disease.PMID:36585694 | DOI:10.1186/s12944-022-01765-0

Nat Cancer. 2022 Dec 30. doi: 10.1038/s43018-022-00489-5. Online ahead of print.ABSTRACTInhibiting individual histone deacetylase (HDAC) is emerging as well-tolerated anticancer strategy compared with pan-HDAC inhibitors. Through preclinical studies, we demonstrated that the sensitivity to the leading HDAC6 inhibitor (HDAC6i) ricolinstat can be predicted by a computational network-based algorithm (HDAC6 score). Analysis of ~3,000 human breast cancers (BCs) showed that ~30% of them could benefice from HDAC6i therapy. Thus, we designed a phase 1b dose-escalation clinical trial to evaluate the activity of ricolinostat plus nab-paclitaxel in patients with metastatic BC (MBC) (NCT02632071). Study results showed that the two agents can be safely combined, that clinical activity is identified in patients with HR+/HER2- disease and that the HDAC6 score has potential as predictive biomarker. Analysis of other tumor types also identified multiple cohorts with predicted sensitivity to HDAC6i's. Mechanistically, we have linked the anticancer activity of HDAC6i's to their ability to induce c-Myc hyperacetylation (ac-K148) promoting its proteasome-mediated degradation in sensitive cancer cells.PMID:36585452 | DOI:10.1038/s43018-022-00489-5

Sci Rep. 2022 Dec 30;12(1):22585. doi: 10.1038/s41598-022-26322-8.ABSTRACTDilated cardiomyopathy (DCM), caused by genetic and environmental factors, usually progresses to heart failure, a major cause of death in elderly people. A diet-associated form of DCM was recently identified in pet dogs eating non-traditional (NT) diets. To identify potential dietary causes, we analyzed metabolomic signatures and gene set/pathway enrichment in (1) all dogs based on disease, diet, and their interactions and (2) dogs with DCM based on diet. Metabolomic analysis was performed in 38 dogs with DCM eating NT diets (DCM-NT), 8 dogs with DCM eating traditional diets, 12 healthy controls eating NT diets, and 17 healthy controls eating traditional diets. Overall, 153 and 63 metabolites differed significantly between dogs with DCM versus healthy controls and dogs eating NT versus traditional diets, respectively, with 12 metabolites overlapping both analyses. Protein-protein interaction networks and gene set enrichment analysis identified 105 significant pathways and gene sets including aging-related pathways (e.g., nuclear factor-kappa B, oxidative damage, inflammation). Seventeen metabolites differed significantly in dogs with DCM eating NT versus traditional diets (e.g., fatty acids, amino acids, legume biomarkers), suggesting different mechanisms for primary versus diet-associated DCM. Our multifaceted metabolomic assessment of DCM in dogs highlighted diet's role in some forms of DCM.PMID:36585421 | DOI:10.1038/s41598-022-26322-8

Trends Plant Sci. 2022 Dec 28:S1360-1385(22)00327-2. doi: 10.1016/j.tplants.2022.12.006. Online ahead of print.ABSTRACTPhytohormones have crucial roles in plant growth, development, and acclimation to environmental stress; however, measuring phytohormone levels and unraveling their complex signaling networks and interactions remains challenging. Mass spectrometry (MS) has revolutionized the study of complex biological systems, enabling the comprehensive identification and quantification of phytohormones and their related targets. Here, we review recent advances in MS technologies and highlight studies that have used MS to discover and analyze phytohormone-mediated molecular events. In particular, we focus on the application of MS for profiling phytohormones, elucidating phosphorylation signaling, and mapping protein interactions in plants.PMID:36585336 | DOI:10.1016/j.tplants.2022.12.006

BMJ Open. 2022 Dec 30;12(12):e069116. doi: 10.1136/bmjopen-2022-069116.ABSTRACTINTRODUCTION: Children who are HIV-exposed uninfected (HEU), that is, children who do not acquire HIV infection despite being born to mothers with HIV, have a higher risk of mortality, infectious morbidity and growth deficits than children who are HIV-unexposed uninfected (HUU). Prior research has focused on breast feeding and has pointed to changes in human milk oligosaccharides (HMOs) associated with maternal HIV that may influence the infant microbiome and thereby lead to these adverse outcomes. However, to our knowledge, no study has attempted to intervene along this pathway to reduce the occurrence of the adverse outcomes in children HEU. We will conduct a double-blind, randomised trial of a synbiotic intervention, which combines an HMO and probiotic, in breastfed infants HEU in South Africa to evaluate whether this intervention has promise to reduce excess infectious morbidity and growth faltering compared with controls.METHODS AND ANALYSIS: One hundred and forty-four breastfed infants HEU, aged 4 weeks, will be 1:1 randomised to receive either a daily synbiotic or an identical-looking placebo through age 24 weeks. Infants will be followed until age 48 weeks and outcomes of infectious morbidity, growth and biological measurements (eg, microbiota, inflammation and metabolome) will be assessed. Analyses will follow intention-to-treat principles comparing the cohorts as randomised. Infants HEU will be compared across arms with respect to the occurrence of infectious morbidity and growth outcomes through 4-24 weeks and 4-48 weeks using appropriate parametric and non-parametric statistical tests. Additionally, an observational cohort of 40 breastfed infants HUU will be recruited as a comparator group with no intervention.ETHICS AND DISSEMINATION: Ethical approval for this study has been obtained from the ethics committees at Columbia University and Stellenbosch University. The findings will be disseminated in publications.TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT05282485. SANCTR ID number: DOH-27-122021-6543.PMID:36585139 | DOI:10.1136/bmjopen-2022-069116

J Adv Res. 2023 Jan;43:233-245. doi: 10.1016/j.jare.2022.02.011. Epub 2022 Feb 22.ABSTRACTINTRODUCTION: Type 1 diabetes (T1D) causes cognitive decline and has been associated with brain metabolic disorders, but its potential molecular mechanisms remain unclear.OBJECTIVES: The purpose of this study was to explore the molecular mechanisms underlying T1D-induced cognitive impairment using metabolomics and lipidomics.METHODS: We developed an optimized integration approach of metabolomics and lipidomics for brain tissue based on UPLC-Q-TOF-MS and analyzed a comprehensive characterization of metabolite and lipid profiles in the hippocampus and frontal cortex of T1D male mice with cognitive decline (T1DCD) and age-matched control (CONT) mice.RESULTS: The results show that T1DCD mice had brain metabolic disorders in a region-specific manner relative to CONT mice, and the frontal cortex exhibited a higher lipid peroxidation than the hippocampus in T1DCD mice. Based on metabolic changes, we found that microglia was activated under diabetic condition and thereby promoted oxidative stress and neuroinflammation, leading to neuronal injury, and this event was more pronounced in the frontal cortex than the hippocampus.CONCLUSION: Our results suggest that brain region-specific shifts in oxidative stress and neuroinflammation may contribute to diabetic cognitive decline, and the frontal cortex could be the more vulnerable brain region than the hippocampus.PMID:36585111 | DOI:10.1016/j.jare.2022.02.011

BMJ Open Diabetes Res Care. 2022 Dec;10(6):e003105. doi: 10.1136/bmjdrc-2022-003105.ABSTRACTINTRODUCTION: Insulin is an essential medicine in the management of diabetes. When stored at high temperatures(HTs), its efficacy could rapidly decline. Therefore, appropriate storage of in-use insulin is necessary to achieve its maximum therapeutic effects. However, the ambient temperature in tropical countries is normally relatively high. This study aimed to compare the efficacies of basal insulin in a pen previously kept at 37°C for 21 days and basal insulin in a refrigerated pen (2°C-8°C). Continuous glucose monitoring (CGM) was used to evaluate daily mean glucose levels (MGLs).RESEARCH DESIGN AND METHODS: This randomized controlled, crossover, equivalence trial recruited adults with type 2 diabetes mellitus and glycated hemoglobin levels <8% who had used insulin glargine for >3 months. Subjects were randomized for sequential use of refrigerated basal insulin followed by basal insulin kept at HT, with a 2-week washout between phases. The HT insulin pens were stored in a 37°C incubator for 21 days before use, while the refrigerated insulin pens were stored at 2°C-8°C. Study patients received 7-day CGM. The primary outcome was the difference in the groups' MGLs. The secondary outcome parameters were glucose variability represented by the standard deviation (SD), mean amplitude of glycemic excursion (MAGE), and percentage of time in range (TIR). The remaining quantity of insulin was evaluated by ultrahigh-performance liquid chromatography (UHPLC) assay.RESULTS: Forty patients completed the study. The MGLwas 158.7±30.5 mg/dL and 157.0±40.9 mg/dL in the HT and refrigerated insulin pen groups, respectively (p=0.72). The groups had no significant differences in MAGE7day, SD, percentage of TIR, carryover period, or treatment effects (all p>0.05). There was also no significant difference in the remaining quantity of insulin evaluated by UHPLC (p=0.97).CONCLUSIONS: HT basal insulin pens retain their potency and have biological activity comparable to that of refrigerated pens.Trial registration number TCTR20210611002.PMID:36585035 | DOI:10.1136/bmjdrc-2022-003105

Clin Chim Acta. 2022 Dec 27:S0009-8981(22)01421-8. doi: 10.1016/j.cca.2022.12.019. Online ahead of print.ABSTRACTBACKGROUND: Maturity-onset diabetes of the young (MODY) patients have unique clinical manifestations and need individualized treatments. We identified novel serum metabolic biomarkers to distinguish MODY and explore the possible mechanism of the clinical manifestation and complications of MODY.METHODS: Fasting serum samples were collected from MODY3 (n=17), MODY2 (n=33), type 1 diabetes (T1DM) (n=34) and healthy individuals (n=30), and were analyzed using the ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) metabolomic platform.RESULTS: 4 metabolites were found significantly fluctuated between groups, including glycerophosphocholine, LysoPC(18:2(9Z,12Z)), sphinganine and L-Phenylalanine. Glycerophosphocholine was selected as a diagnostic biomarker. The the area under the ROC curve (AUC) for distinguishing MODYs from healthy controls and differentiating MODY3 from T1DM reached 1.0. The combination of metabolites also gained good diagnostic value. The AUC of the combination of LysoPC(18:2(9Z,12Z)), sphinganine and L-Phenylalanine for discriminating MODY3 from T1DM was 0.983. Besides, the combination of clinical indices and metabolites helped to better differentiate the 2 MODY subtypes.CONCLUSIONS: We identified the metabolic profiles of MODY2 and MODY3 and found promising biomarkers for distinguishing MODY from T1DM, which provides evidence for the pathogenesis and characteristic clinical manifestations of patients with MODY2 and MODY3.PMID:36584766 | DOI:10.1016/j.cca.2022.12.019

Spectrochim Acta A Mol Biomol Spectrosc. 2022 Dec 17;290:122259. doi: 10.1016/j.saa.2022.122259. Online ahead of print.ABSTRACTThe development of novel platforms for non-invasive continuous glucose monitoring applied in the screening and monitoring of diabetes is crucial to improve diabetes surveillance systems. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy of urine can be an alternative as a sustainable, label-free, fast, non-invasive, and highly sensitive analysis to detect changes in urine promoted by diabetes and insulin treatment. In this study, we used ATR-FTIR to evaluate the urinary components of non-diabetic (ND), diabetic (D), and diabetic insulin-treated (D + I) rats. As expected, insulin treatment was capable to revert changes in glycemia, 24-h urine collection volume, urine creatinine, urea, and glucose excretion promoted by diabetes. Several differences in the urine spectra of ND, D, and D + I were observed, with urea, creatinine, and glucose analytes being related to these changes. Principal components analysis (PCA) scores plots allowed for the discrimination of ND and D + I from D with an accuracy of ∼ 99 %. The PCA loadings associated with PC1 confirmed the importance of urea and glucose vibrational modes for this discrimination. Univariate analysis of second derivative spectra showed a high correlation (r: 0.865, p < 0.0001) between the height of 1074 cm-1 vibrational mode with urinary glucose concentration. In order to estimate the amount of glucose present in the infrared spectra from urine, multivariate curve resolution-alternating least square (MCR-ALS) was applied and a higher predicted concentration of glucose in the urine was observed with a correlation of 78.9 % compared to urinary glucose concentration assessed using enzyme assays. In summary, ATR-FTIR combined with univariate and multivariate chemometric analyses provides an innovative, non-invasive, and sustainable approach to diabetes surveillance.PMID:36584643 | DOI:10.1016/j.saa.2022.122259