-
Diabetes Therapy : Research, Treatment... Aug 2019Ectopic fat accumulation has been found to play a pathophysiological role in insulin resistance, type 2 diabetes (T2DM), and coronary artery diseases. Findings from a...
Rationale, Design for the ASSET Study: A Prospective Randomized Study Comparing Empagliflozin's Effect to Sitagliptin on Cardiac Fat Accumulation/Function in Patients with Type 2 Diabetes.
INTRODUCTION
Ectopic fat accumulation has been found to play a pathophysiological role in insulin resistance, type 2 diabetes (T2DM), and coronary artery diseases. Findings from a number of previous studies suggest that sodium glucose cotransporter 2 (SGLT2) inhibitors reduce lipid accumulation, including myocardial and pericardial fat, while dipeptidyl peptidase 4 (DPP4) inhibitors suppress ectopic lipid accumulation and improve cardiac function. However, a clinical study that precisely explains and compares the efficacy of SGLT2 inhibitors and DPP4 inhibitors on cardiac fat accumulation has not been performed. Moreover, the association between cardiac fat accumulation and cardiac function or metabolic changes, such as tissue-specific insulin resistance, remains unclear. It is our intention to conduct the first study to assess the effects of empagliflozin compared to sitagliptin in reducing ectopic fat accumulation, specifically pericardial fat, and its association with improvement in cardiac function and tissue-specific insulin sensitivity.
METHODS
We have designed a prospective, randomized open-label, and blinded-endpoint study with the intention to enroll 44 Japanese patients with T2DM. The patients are to be divided them into two groups, an empagliflozin group and an sitagliptin group, with the former to be supplemented with empagliflozin 10 mg and the latter to be supplemented with sitagliptin 100 mg, both groups for 12 weeks. The primary endpoint of the study is the change in the amount of pericardial fat. The secondary endpoints are the changes in the amount of intracellular fat in the myocardium, cardiac function, tissue-specific insulin sensitivity, fatty acid metabolism in myocardial tissue, assessed by parameters of iodine-123-β-methyl-iodophenyl pentadecanoic acid myocardial scintigraphy, blood and urine biomarkers, and lifestyle evaluation.
PLANNED OUTCOMES
The results of this study will be available in 2020. The aim of this study is to provide an effective treatment strategy for patients with T2DM by considering cardiac fat accumulation, cardiac function, and insulin resistance.
FUNDING
Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance.
TRIAL REGISTRATION
University Hospital Medical Information Network Clinical Trial Registry: UMIN000026340.
PubMed: 31172455
DOI: 10.1007/s13300-019-0640-4 -
Frontiers in Medicine 2024Hypoxic conditions and () infection are significant factors influencing the prognosis and treatment of patients with bronchiectasis. This study aimed to explore the...
BACKGROUND
Hypoxic conditions and () infection are significant factors influencing the prognosis and treatment of patients with bronchiectasis. This study aimed to explore the potential for breath analysis to detect hypoxic conditions and infection in bronchiectasis patients by analyzing of volatile organic compounds (VOCs) in exhaled breath condensate (EBC).
METHODS
EBC samples were collected from stable bronchiectasis patients and analyzed using solid phase microextraction-gas chromatography-mass spectrometry (SPME-GCMS). The association of VOCs with bronchiectasis patients' phenotypes including hypoxic conditions and isolation was analyzed, which may relate to the severity of bronchiectasis disease.
RESULTS
Levels of 10-heptadecenoic acid, heptadecanoic acid, longifolene, and decanol in the hypoxia group were higher compared to the normoxia group. Additionally, the levels of 13-octadecenoic acid, octadecenoic acid, phenol, pentadecanoic acid, and myristic acid were increased in (+) group compared to the (-) group. Subgroup analysis based on the bronchiectasis severity index (BSI)reveled that the levels of 10-heptadecenoic acid, heptadecanoic acid, decanol, 13-octadecenoic acid, myristic acid, and pentadecanoic acid were higher in the severe group compared to the moderate group. Multivariate linear regression showed that 10-heptadecenoic acid and age were independent prognostic factors for bronchiectasis patients with hypoxia. Furthermore, octadecenoic acid, phenol and gender were identified as independent prognostic factors for bronchiectasis patients with isolation.
CONCLUSION
The study provides evidence that specific VOCs in EBC are correlated with the severity of bronchiectasis, and 10-heptadecenoic acid is shown to be a predictive marker for hypoxia condition in bronchiectasis patients.
PubMed: 38633315
DOI: 10.3389/fmed.2024.1345165 -
Circulation Journal : Official Journal... Sep 2020
I-β-Methyl Iodophenyl Pentadecanoic Acid and Thallium Dual Myocardial Single-Photon Emission Computed Tomography (BMIPP/Tl SPECT) Detection of Myocardial Damage of Systemic Sclerosis.
Topics: Aged; Fatty Acids; Female; Humans; Iodine Radioisotopes; Iodobenzenes; Japan; Middle Aged; Myocardial Perfusion Imaging; Nicorandil; Scleroderma, Systemic; Thallium Radioisotopes; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Vasodilator Agents; Ventricular Dysfunction, Left
PubMed: 32848121
DOI: 10.1253/circj.CJ-20-0516 -
Microorganisms Oct 2023The emergence of multidrug-resistant pathogens creates public health challenges, prompting a continuous search for effective novel antimicrobials. This study aimed to...
The emergence of multidrug-resistant pathogens creates public health challenges, prompting a continuous search for effective novel antimicrobials. This study aimed to isolate marine actinomycetes from South Africa, evaluate their in vitro antimicrobial activity against and Shiga toxin-producing , and characterize their mechanisms of action. Marine actinomycetes were isolated and identified by 16S rRNA sequencing. Gas chromatography-mass spectrometry (GC-MS) was used to identify the chemical constituents of bioactive actinomycetes' secondary metabolites. Antibacterial activity of the secondary metabolites was assessed by the broth microdilution method, and their mode of actions were predicted using computational docking. While five strains showed antibacterial activity during primary screening, only strain SOD(B)ST2SA2 exhibited activity during secondary screening for antibacterial activity. GC-MS identified five major bioactive compounds: 1-octadecene, diethyl phthalate, pentadecanoic acid, 6-octadecenoic acid, and trifluoroacetoxy hexadecane. SOD(B)ST2SA2's extract demonstrated minimum inhibitory concentration and minimum bactericidal concentration, ranging from 0.78-25 mg/mL and 3.13 to > 25 mg/mL, respectively. Diethyl phthalate displayed the lowest bacterial protein-binding energies (kcal/mol): -7.2, dihydrofolate reductase; -6.0, DNA gyrase B; and -5.8, D-alanine:D-alanine ligase. Thus, marine SOD(B)ST2SA2 is a potentially good source of antibacterial compounds that can be used to control STEC and .
PubMed: 37894198
DOI: 10.3390/microorganisms11102539 -
International Journal of Microbiology 2022Knowledge on human skin microbiota composition has been expanding in recent years. Its role in human health and disease represents an active area of investigation. As...
Knowledge on human skin microbiota composition has been expanding in recent years. Its role in human health and disease represents an active area of investigation. As part of our culturomics project that consists of exploring the human microbiota by isolating bacteria through innovative culture-dependent methods, we isolated a new bacterial strain from the back of the right hand, in a 67-year-old healthy woman. Here, we characterize the strain Marseille-Q2903 by the taxonogenomic approach. Marseille-Q2903 exhibits a 99.5% 16S rRNA sequence similarity with but with only 92% of coverage. The closest species based on a 100% coverage of the 16S sequence is with an identity similarity of 97.63%. Furthermore, digital DNA-DNA hybridization reveals a maximum identity similarity of only 31.5% and an OrthoANI parameter provided a value of 86.95% between Marseille-Q2903 and . Marseille-Q2903 is a yellowish-pigmented, Gram-positive, coccoid shaped, and facultative aerobic bacterium, and belonging to the Dermabacteraceae family. The major fatty acids detected are 12-methyl-tetradecanoic acid (69%), 14-methyl-hexadecanoic acid (16%), and 14-methyl-pentadecanoic acid (7%). Marseille-Q2903 genome size is of 3,073,790 bp, with a 70.43% G + C content. Taken altogether, these results confirm the status of this strain as a new member of the genus for which the name of sp. strain Marseille-Q2903 is proposed (=CSURQ2903 = CECT30363).
PubMed: 35392139
DOI: 10.1155/2022/2875994 -
Journal of Interpersonal Violence Nov 2022The attachment theory has commonly been used to examine intimate partner psychological aggression (IPPA), but few studies have examined its association with...
The attachment theory has commonly been used to examine intimate partner psychological aggression (IPPA), but few studies have examined its association with self-reported justifications for one's own use of IPPA. Behaviors, including the use of IPPA, are influenced, maintained, and function within the context of their justifications, highlighting the importance of investigating these justifications to obtain a clearer picture of IPPA. This study examined whether insecure romantic attachment (i.e., attachment anxiety and attachment avoidance) in both partners of a couple was associated with their justifications for their own use of IPPA. A community sample of 81 mixed-sex couples who reported using IPPA in the last year completed self-reported questionnaires on adult romantic attachment and their justifications for their use of IPPA. Results of a path analysis based on the actor-partner interdependence model revealed moderate positive associations between attachment anxiety and one's use of internal and external justifications for their IPPA perpetration in men and women. An unexpected dyadic positive association is discussed. These results suggest that the use of justifications for one's use of IPPA may reflect a strategy of hyperactivation that could contribute to the cycle of psychological aggression. Uncovering the function of these justifications could provide important therapeutic benefits, which are discussed in the study's implications.
Topics: Adult; Aggression; Anxiety; Female; Humans; Interpersonal Relations; Intimate Partner Violence; Iodobenzenes; Male; Sexual Partners
PubMed: 34791928
DOI: 10.1177/08862605211055156 -
Scientific Reports Aug 2019The aim of the study was to discover the metabolomic changes in plasma that occur during human Ischemia-Reperfusion (I/R) injury and to evaluate the diagnostic utility...
Metabolomic characterization of myocardial ischemia-reperfusion injury in ST-segment elevation myocardial infarction patients undergoing percutaneous coronary intervention.
The aim of the study was to discover the metabolomic changes in plasma that occur during human Ischemia-Reperfusion (I/R) injury and to evaluate the diagnostic utility of plasma metabolomic biomarkers for determination of myocardial injury. Deciphering the details of plasma metabolome in ST-segment elevation myocardial infarction (STEMI) patients before and after primary percutaneous coronary interventions (PPCI) would allow for better understanding of the mechanisms involved during acute myocardial ischemia and reperfusion in humans. We performed a detailed non-targeted metabolomic analysis of plasma from 27 STEMI patients who had undergone PPCI in the first 48 hrs employing a LC-MS approach. Plasma metabolome at ischemic condition was compared to multiple time points after PPCI which allowed us to focus on changes in the reperfusion phase. Classification of the differential metabolites based on chemical taxonomy identified a major role for lipids and lipid-derived molecules. Biochemical pathway analysis identified valine, leucine and isoleucine biosynthesis, vitamin B6 metabolism and glutathione metabolism as the most significant metabolic pathways representing early response to I/R injury. We also identified phenyl alanine, tyrosine, linoleic acid and glycerophospholipid metabolism as the most significant pathways representing late response to I/R injury. A panel of three metabolites pentadecanoic acid, linoleoyl carnitine and 1-linoleoylglycerophosphocholine was discovered to have diagnostic value in determining the extent of I/R injury based on cardiac biomarkers. Using a non-targeted LC-MS approach, we have successfully generated the most comprehensive data to date on significant changes in the plasma metabolome in STEMI patients who had undergone PPCI in the first 48 hrs showing that lipid metabolites represent the largest cohort of molecules undergoing significant change.
Topics: Adolescent; Adult; Aged; Biomarkers; Comorbidity; Computational Biology; Female; Humans; Male; Metabolomics; Middle Aged; Myocardial Reperfusion Injury; Percutaneous Coronary Intervention; ROC Curve; ST Elevation Myocardial Infarction; Time Factors; Treatment Outcome; Young Adult
PubMed: 31409856
DOI: 10.1038/s41598-019-48227-9 -
Frontiers in Genetics 2020According to the traditional Chinese medicine (TCM) system, Chinese herbal medicines (HMs) can be divided into four categories: hot, warm, cold, and cool. A cool nature...
According to the traditional Chinese medicine (TCM) system, Chinese herbal medicines (HMs) can be divided into four categories: hot, warm, cold, and cool. A cool nature usually is categorized as a cold nature, and a warm nature is classified as a hot nature. However, the detectable characteristics of the gene expression profile associated with the cold and hot properties have not been studied. To address this question, a strategy for the cross-species annotation of conserved genes was established in the present study by using transcriptome data of 20 HMs with cold and hot properties. Functional enrichment analysis was performed on group-specific expressed genes inferred from the functional genome of the reference species (i.e., ). Results showed that metabolic pathways relevant to chrysoeriol, luteolin, paniculatin, and wogonin were enriched for cold-specific genes, and pathways of inositol, heptadecane, lauric acid, octanoic acid, hexadecanoic acid, and pentadecanoic acid were enriched for hot-specific genes. Six functional modules were identified in the HMs with the cold property: nucleotide biosynthetic process, peptidy-L-cysteine -palmitoylation, lipid modification, base-excision repair, dipeptide transport, and response to endoplasmic reticulum stress. For the hot HMs, another six functional modules were identified: embryonic meristem development, embryonic pattern specification, axis specification, regulation of RNA polymerase II transcriptional preinitiation complex assembly, mitochondrial RNA modification, and cell redox homeostasis. The research provided a new insight into HMs' cold and hot properties from the perspective of the gene expression profile of plants.
PubMed: 32625232
DOI: 10.3389/fgene.2020.00532 -
Nutrients Apr 2023Epidemiological studies found that the intake of dairy products is associated with an increased amount of circulating odd-chain fatty acids (OCFA, C15:0 and C17:0) in...
Epidemiological studies found that the intake of dairy products is associated with an increased amount of circulating odd-chain fatty acids (OCFA, C15:0 and C17:0) in humans and further indicate that especially C17:0 is associated with a lower incidence of type 2 diabetes. However, causal relationships are not elucidated. To provide a mechanistic link, mice were fed high-fat (HF) diets supplemented with either milk fat or C17:0 for 20 weeks. Cultured primary mouse hepatocytes were used to distinguish differential effects mediated by C15:0 or C17:0. Despite an induction of OCFA after both dietary interventions, neither long-term milk fat intake nor C17:0 supplementation improved diet-induced hepatic lipid accumulation and insulin resistance in mice. HF feeding with milk fat actually deteriorates liver inflammation. Treatment of primary hepatocytes with C15:0 and C17:0 suppressed JAK2/STAT3 signaling, but only C15:0 enhanced insulin-stimulated phosphorylation of AKT. Overall, the data indicate that the intake of milk fat and C17:0 do not mediate health benefits, whereas C15:0 might be promising in further studies.
Topics: Humans; Animals; Mice; Insulin Resistance; Diabetes Mellitus, Type 2; Fatty Acids; Fatty Liver; Diet, High-Fat
PubMed: 37432205
DOI: 10.3390/nu15092052 -
Heliyon Aug 2021Allium species are medically important plants, rich in bioactive molecules with antitumoral properties. In this study, we aimed to investigate the molecular composition...
Allium species are medically important plants, rich in bioactive molecules with antitumoral properties. In this study, we aimed to investigate the molecular composition and anticancer activities of Holmboe, an endemic Allium species of the island of Cyprus. GC-MS analysis of ethanolic extracts of H. bulb (AWB) showed bioactive molecules, octadecanoic acid 2-hydroxy-1-(hydroxymethyl)ethyl ester (21.99 %), hexadecanoic acid (20.42 %), pentadecanoic acid (9.19 %), 1,2-benzenedicarboxylic acid, diethyl ester (8.79 %), with known anticancer activities. AWB exerted significant reduction in mitochondria dependent metabolic activity as a measure of cell growth on MCF-7 (weakly metastatic) and MDA-MB-231 (strongly metastatic) human breast cancer (BCa) cell lines with a more prominent effect on highly metastatic BCa cells. Both trypan blue and lactate dehydrogenase (LDH) cytotoxicity assays quantitatively revealed that exposure to AWB extract significantly reduced cancer cell viability in both tested cell types. Differential activation of caspases in the tested cell lines indicated faster apoptotic activity on MDA-MB-231 cells compared to MCF-7. A significant reduction in cell motility was demonstrated upon AWB exposure of MCF-7 and MDA-MB-231 cells. AWB bioactive molecules collectively act on cancer cells to exert significant cytotoxic, apoptotic activities on both MCF-7 and MDA-MB-231 cells and significantly reduce their lateral motility, elucidating AWB as a promising agent to further be utilized in anticancer studies.
PubMed: 34401594
DOI: 10.1016/j.heliyon.2021.e07730