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Molecules (Basel, Switzerland) Mar 2023The spread of antibiotic-resistant opportunistic microbes is a huge socioeconomic burden and a growing concern for global public health. In the current study, two...
The spread of antibiotic-resistant opportunistic microbes is a huge socioeconomic burden and a growing concern for global public health. In the current study, two endophytic fungal strains were isolated from roots and identified as MT597434.1 and KU324798.1. Secondary metabolites produced by and were extracted and tested for their antimicrobial activity. The highest activity was noticed against and treated with and secondary metabolites, respectively. crude extract was mainly composed of Pentadecanoic acid, 14-methyl-, methyl ester and 9-Octadecenoic acid ()-, methyl ester (26.66 and 18.01%, respectively), while crude extract's major components were 2,4-Decadienal, (,) and 9-Octadecenoic acid ()-, and methyl ester (10.69 and 10.32%, respectively). Moreover, a comparative study between the fungal extracts and dicationic pyridinium iodide showed that the combination of and secondary metabolites with dicationic pyridinium iodide compound showed a synergistic effect against . The combined formulae inhibited the bacterial growth after 4 to 6 h through cell wall breakage and cells deformation, with intracellular components leakage and increased ROS production.
Topics: Iodides; Escherichia coli; Oleic Acid; Aspergillus niger; Complex Mixtures
PubMed: 36985405
DOI: 10.3390/molecules28062434 -
European Heart Journal. Case Reports Mar 2023Cardiovascular events, including pericarditis, myocarditis, and myocardial ischaemia, have been reported as complications following COVID-19 vaccination.
BACKGROUND
Cardiovascular events, including pericarditis, myocarditis, and myocardial ischaemia, have been reported as complications following COVID-19 vaccination.
CASE SUMMARY
A 28-year-old Japanese woman diagnosed 10 years earlier with systemic lupus erythematosus and antiphospholipid syndrome was admitted to our hospital because of chest pain and Raynaud's phenomenon. She had received a second dose of the COVID-19 BNT162b2 mRNA vaccine 28 days earlier. I-β-methyl iodophenyl pentadecanoic acid (BMIPP) and thallium dual myocardial single-photon emission computed tomography demonstrated mildly reduced perfusion of BMIPP in the mid-anterior wall of the left ventricle. Coronary angiography revealed normal coronary arteries; additionally, an endomyocardial biopsy was performed. Histopathological evaluation revealed a normal myocardium without cell infiltration. However, immunostaining for the severe acute respiratory coronavirus (SARS-CoV)/severe acute respiratory coronavirus 2 (SARS-CoV-2) spike protein was positive in the small intramural coronary arteries. The administration of azathioprine (50 mg/day) and amlodipine (5 mg/day) and increases in her prednisolone (10 mg/day) and aspirin doses led to improvements in the symptoms of the patient.
DISCUSSION
Our data lead us to speculate that two events in the timeline of the patient, namely, receiving COVID-19 vaccination and the presence of SARS-CoV/SARS-CoV-2 spike protein in small intramural coronary arteries, may be related to the myocardial microangiopathy observed in this patient.
PubMed: 36909840
DOI: 10.1093/ehjcr/ytad102 -
Molecular Genetics and Metabolism... Mar 2023Primary triglyceride deposit cardiomyovasculopathy (P-TGCV), caused by a rare genetic mutation in encoding adipose triglyceride lipase (ATGL), exhibits severe...
Primary triglyceride deposit cardiomyovasculopathy (P-TGCV), caused by a rare genetic mutation in encoding adipose triglyceride lipase (ATGL), exhibits severe cardiomyocyte steatosis and heart failure. Here, we report the case of a 51-year-old man with P-TGCV homozygous for a novel mutation (c.446C > G, P149R) in the catalytic domain of ATGL. Analyses of endomyocardial biopsy specimens and expression experiments showed mutant protein expression with conserved lipid binding, but reduced lipolytic activity, indicating mutation pathogenicity.
PubMed: 36846631
DOI: 10.1016/j.ymgmr.2023.100960 -
Nutrients Feb 2023The mechanism of hypertension in children remains elusive. The objective of this study was to analyze plasma metabolomics characteristics to explore the potential...
The mechanism of hypertension in children remains elusive. The objective of this study was to analyze plasma metabolomics characteristics to explore the potential mechanism of hypertension in children. Serum samples from 29 control children, 38 children with normal body mass index and simple hypertension (NBp), 8 children overweight with simple hypertension (OBp), 37 children with normal body mass index and H-type hypertension (NH) and 19 children overweight with H-type hypertension (OH) were analyzed by non-targeted metabolomics. A total of 1235 differential metabolites were identified between children with hypertension and normal controls, of which 193 metabolites including various lipids were significantly expressed. Compared with the control group, 3-dehydroepiandrosterone sulfate, oleic acid and linoleic acid were up-regulated, and gamma-muricholic acid was down-regulated in the NBp group; 3-dehydroepiandrosterone sulfate, 4-acetamidobutanoate and 1-hexadecanoyl-2-octadecadienoyl-sn-glyero-3-phosphocholine were up-regulated in the OBp group, whereas adenosine and 1-myristoyl-sn-glyero-3-phosphocholine were down-regulated; in the NH group, 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine, phenol and 3-methoxytyramine were up-regulated, while pentadecanoic acid was down-regulated; in the OH group, NG,NG-dimethyl-L-arginine, 1-palmitoyl-sn-glycero-3-phosphocholine and monoethyl phthalate were up-regulated, while phloretin and glycine were down-regulated. The results showed that the children with hypertension had obvious disorders of lipid metabolism (especially in the overweight hypertension group), which led to the occurrence of hypertension. Additionally, the concentration of NO production-related NG, NG-dimethyl-L-arginine, was significantly increased, which may play an important role in H-type hypertension in children.
Topics: Humans; Child; Chromatography, High Pressure Liquid; Phosphorylcholine; Dehydroepiandrosterone Sulfate; Overweight; Metabolomics; Hypertension; Biomarkers
PubMed: 36839194
DOI: 10.3390/nu15040836 -
International Journal of Pharmaceutics Mar 2023Human serum albumin (HSA) is an important nanocarrier of hydrophobic drugs due to its biocompatibility, bioresorbability, non-immunogenicity and intrinsic targetability....
Human serum albumin (HSA) is an important nanocarrier of hydrophobic drugs due to its biocompatibility, bioresorbability, non-immunogenicity and intrinsic targetability. However, HSA/drug nanocomplexes have to experience complicated manufacturing process including multiple high-pressure homogenization and removing organic solvent under reduced pressure condition. Besides, the clinical application of these HSA/drug nanocomplexes is often limited because of their unsatisfactory stability and restricted dose. To overcome these issues, a redox-responsive paclitaxel-pentadecanoic acid prodrug conjugate embedded human serum albumin nanoparticles (NPs) was developed as a model in this report. First, PTX was activated and conjugated with 11-mercaptoundecanoic acid through a disulfide bond. The resultant disulfide bond bridged paclitaxel-pentadecanoic acid conjugate (PTX-SS-C10-COOH) was characterized by NMR and MS. After that, PTX-SS-C10-COOH dissolved in ethanol was mixed with HSA in water followed by lyophilization to generate HSA/PTX-SS-C10-COOH nanoparticles (HPTX NPs). Dynamic light scattering (DLS) and transmission electron microscopy (TEM) characterization indicated that the HPTX NPs have spherical structure with an average diameter of approximately 120 nm. The formation of HSA/PTX-SS-C10-COOH NPs was confirmed by fluorescence quenching technology, ascribed to electrostatic and hydrophobic interactions. The HPTX NPs displayed a highdrug loading of 29.78 % and an entrapment efficiency of 94.16 %. Their reduced responsiveness was validated by glutathione (GSH)-triggered fast release of PTX. The pharmacokinetics, antitumor efficacy and systemic toxicity of HPTX NPs were thoroughly evaluated. The results showed that the HPTX NPs had longer retention, more effective tumor growth inhibition and lower toxicity compared with commercialized Taxol®. Importantly, the HPTX NPs could be administered at much high dose to achieve a significant tumor growth inhibition compared with Abraxane®. Together, the redox-responsive HPTX NPs with high drug loading is a promising strategy to deliver PTX for cancer chemotherapy.
Topics: Humans; Paclitaxel; Serum Albumin, Human; Nanoparticles; Neoplasms; Oxidation-Reduction; Disulfides; Cell Line, Tumor
PubMed: 36822341
DOI: 10.1016/j.ijpharm.2023.122761 -
Nutrients Feb 2023Increasingly, studies have discovered that different fatty acids (Fas) are linked to colorectal cancer (CRC) risk. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Increasingly, studies have discovered that different fatty acids (Fas) are linked to colorectal cancer (CRC) risk.
METHODS
We systematically searched Embase and Medline databases to identify eligible studies that examined the associations of different types of Fas with CRC risk. The effect estimates and their 95% confidence intervals (Cis) were pooled using a random-effects model. Subgroup and sensitivity analyses were performed to examine the robustness of the study findings.
RESULTS
This study evaluated the associations of 28 dietary and 18 blood Fas with CRC risk by summarizing the most updated evidence from 54 observational and four Mendelian Randomization (MR) studies. The present findings suggested that high dietary intake of eicosapentaenoic acid (EPA), docosahexanoic acid (DHA), and docosapentaenoic acid (DPA) are related to low risk of CRC, while the -6/-3 PUFA ratio and trans-FA are related to high risk of CRC. The summary of all cohort studies found that a high intake of SFA and DHA was a protective factor for CRC, and a high intake of the -6/-3 PUFA ratio was a risk factor for CRC. In the subgroup analysis of cancer subsites, we found that the dietary intake of linoleic acid (LA) and trans-FA are risk factors, while DPA is a protective factor for colon cancer. High dietary DHA intake was associated with a lower risk of rectal cancer, while the dietary -6/-3 PUFA ratio was associated with a higher risk of rectal cancer. Meta-analysis of blood FA levels showed a significant reverse association between blood pentadecanoic acid and CRC risk, whilst other blood Fas showed no significant association with CRC risk. All included MR studies showed that high plasma arachidonic acid (AA) is associated with increased CRC risk.
CONCLUSIONS
Current evidence on the dietary intake and blood levels of Fas in relation to CRC risk is less consistent. Future studies are needed to investigate how the metabolism of Fas contributes to CRC development.
Topics: Humans; Fatty Acids; Fatty Acids, Omega-3; Eating; Risk Factors; Colorectal Neoplasms; Rectal Neoplasms; Observational Studies as Topic
PubMed: 36771436
DOI: 10.3390/nu15030730 -
Environmental Science and Pollution... Apr 2023The present study explored the process of bioremediation, sequestration of carbon dioxide, and biofuel production using multifarious potent freshwater microalgae...
The present study explored the process of bioremediation, sequestration of carbon dioxide, and biofuel production using multifarious potent freshwater microalgae Tetradesmus obliquus TS03. The heavy metals were reduced, viz., 8.34 mg of cadmium (95.13%), 4.56 mg of chromium (97.28%), 1.34 mg of copper (98.67%), 1.24 mg of cobalt (98.19%), 1.93 mg of lead (96.72%), 2.31 mg of nickel (97.14%), and 2.23 mgL of zinc (96.59%) using photobioreactor microalgal treatment method. The heavy metal biosorption capacity rate (q) was 98.90% determined by the Langmuir and Freundlich isotherm kinetics model at 10 days of effluent treatment using Tetradesmus obliquus TS03. The microalgae T. obliquus TS03 utilized 98.34% of carbon dioxide (CO) enhanced by acetyl CoA carboxylase and RuBisCO enzymes. The biodiesel was extracted from microalga and identified 32 fatty acid methyl ester major compounds viz., tetradecanoate methyl ester, hexadecanoic acid methyl ester, tridecanoic acid methyl ester, heptadecatrienoic acid methyl ester, octadecanoic acid methyl ester, eicosanoic acid methyl ester, pentadecanoic acid methyl ester, and cis-methylicosanoate using gas mass chromatography (GCMS). The biodiesel functional groups were identified, viz., amides, phenols, alcohols, alkynes, carboxylic acids, carbonyls, and ketones groups using Fourier transformation infrared (FTIR). The bioethanol was identified using high-performance liquid chromatography (HPLC) and determined the peak presented at RT of 4.35 min (75,693.1046 µV s).
Topics: Carbon Dioxide; Microalgae; Biofuels; Chlorophyceae; Esters; Biomass
PubMed: 36752925
DOI: 10.1007/s11356-023-25703-4 -
Frontiers in Endocrinology 2023To study the effect of Guilu Erxian ointment on the outcome of IVF-ET in older patients with poor ovarian response infertility of kidney-qi deficiency type, and to... (Randomized Controlled Trial)
Randomized Controlled Trial
Mechanism of Guilu Erxian ointment based on targeted metabolomics in intervening fertilization and embryo transfer outcome in older patients with poor ovarian response of kidney-qi deficiency type.
OBJECTIVE
To study the effect of Guilu Erxian ointment on the outcome of IVF-ET in older patients with poor ovarian response infertility of kidney-qi deficiency type, and to verify and analyze the mechanism of action of traditional Chinese medicine on improving older patients with poor ovarian response infertility of kidney-qi deficiency type from the perspective of metabolomics using targeted metabolomics technology, identify the related metabolic pathways, and provide metabolic biomarker basis and clinical treatment ideas for improving older patients with poor ovarian response infertility.
METHODS
This study was a double-blind, randomized, placebo-controlled trial, and a total of 119 infertile patients who underwent IVF-ET at Shandong Center for Reproduction and Genetics of Integrated Traditional Chinese and Western Medicine were selected. Eighty older patients with infertility undergoing IVF were randomly divided into older treatment group and older placebo group, and another 39 young healthy women who underwent IVF-ET or ICSI due to male factors were selected as the normal control group. Flexible GnRH antagonist protocol was used for ovulation induction in all three groups, and Guilu Erxian ointment and placebo groups started taking Guilu Erxian ointment and placebo from the third day of menstruation until IVF surgery. And ultra-high performance liquid chromatography-triple quadrupole mass spectrometer (UHPLC-QTRAP MS) was used to detect metabolites in the three groups of samples.
RESULTS
Compared with the placebo group, the number of oocytes retrieved, 2PN fertilization, high-quality embryos, total number of available embryos and estrogen on HCG day were increased in the treatment group, and the differences were statistically significant ( > 0.05), but the clinical pregnancy rate of fresh embryos and frozen embryos were not statistically significant ( > 0.05). The results of targeted metabolomics analysis showed that follicular fluid in the treatment group clustered with the normal young group and deviated from the placebo group. A total of 55 significant differential metabolites were found in the follicular fluid of older patients with poor ovarian response of kidney-qi deficiency type and patients in the normal young group, after Guilu Erxian ointment intervention, Metabolites such as L-Aspartic acid, Glycine, L-Serine, Palmitoleic Acid, Palmitelaidic acid, L-Alanine, Gamma-Linolenic acid, Alpha-Linolenic Acid, and N-acetyltryptophan were down-regulated, mainly involving amino acid metabolism and fatty acid metabolism.
CONCLUSION
Guilu Erxian ointment can effectively improve the clinical symptoms and IVF outcomes of older patients with poor ovarian response of kidney-qi deficiency type. There were differences in follicular fluid metabolites between older patients with poor ovarian response of kidney-qi deficiency type and normal women. L-Aspartic acid, L-Alanine, Aminoadipic acid, L-Asparagine, L-Arginine, L-Serine, Gamma- Linolenic acid, Pentadecanoic acid and Alpha-Linolenic Acid are closely related to older patients with poor ovarian response due to deficiency of kidney-qi and may be inferred as biomarkers. The mechanism of Guilu Erxian ointment intervention may be mainly through amino acid metabolism and fatty acid metabolism regulation.
Topics: Pregnancy; Humans; Male; Female; Aspartic Acid; Ointments; Qi; alpha-Linolenic Acid; Fertilization in Vitro; Embryo Transfer; Infertility, Female; Kidney
PubMed: 36742408
DOI: 10.3389/fendo.2023.1045384 -
Journal of Medicinal Food Mar 2023Odd-chain saturated fatty acids generally serve as specific biomarkers of dietary components and dairy intake, some of which have anticancer properties. This study was...
Odd-chain saturated fatty acids generally serve as specific biomarkers of dietary components and dairy intake, some of which have anticancer properties. This study was performed to assess the anticancer effects of heptadecanoic acid (HDNA) in human pancreatic carcinoma cells. MTT (thiazolyl blue tetrazolium bromide) assay showed that HDNA exerted stronger cytotoxic effects than pentadecanoic acid, palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), and linoleic acid (18:2) on both Panc-1 and MIA PaCa-2 pancreatic cancer cells. In addition, HDNA reduced colony formation and induced apoptosis in these pancreatic cancer cells as indicated by Hoechst 33342 staining, Annexin V/propidium iodide staining, cell cycle analysis, and Western blotting analysis in a dose-dependent manner. Moreover, HDNA synergistically reduced cell viability and promoted apoptosis when combined with gemcitabine (GEM), a chemotherapeutic agent commonly used in the treatment of pancreatic cancer. GEM-resistant MIA PaCa-2 (GR-MIA PaCa-2) cells with a resistance indices (RI) value of 215.09 [RI = half-maximal inhibitory concentration (IC) of GR-MIA PaCa-2 cells/IC of MIA PaCa-2 cells] were established, and the efficacy of HDNA on GEM chemosensitivity was confirmed. Surprisingly, HDNA exhibited even higher antiproliferative efficacy against GR-MIA PaCa-2 cells (IC = 71.45 ± 6.37 M) than parental MIA PaCa-2 cells (IC = 77.47 ± 2.10 M). Finally, HDNA treatment inhibited the Hippo pathway and induced apoptosis of GR-MIA PaCa-2 cells. These findings suggest the beneficial effects of a HDNA-rich diet during pancreatic cancer treatments.
Topics: Humans; Gemcitabine; Cell Proliferation; Cell Line, Tumor; Pancreatic Neoplasms; Fatty Acids; Apoptosis
PubMed: 36716276
DOI: 10.1089/jmf.2022.K.0061 -
Frontiers in Cellular and Infection... 2022Chronic atrophic gastritis (CAG), premalignant lesions of gastric cancer (GC), greatly increases the risk of GC. Gastroscopy with tissue biopsy is the most commonly used...
BACKGROUND
Chronic atrophic gastritis (CAG), premalignant lesions of gastric cancer (GC), greatly increases the risk of GC. Gastroscopy with tissue biopsy is the most commonly used technology for CAG diagnosis. However, due to the invasive nature, both ordinary gastroscope and painless gastroscope result in a certain degree of injury to the esophagus as well as inducing psychological pressure on patients. In addition, patients need fast for at least half a day and take laxatives.
METHODS
In this study, fecal metabolites and microbiota profiles were detected by metabolomics and 16S rRNA V4-V5 region sequencing.
RESULTS
Alteration of fecal metabolites and microbiota profiles was found in CAG patients, compared with healthy volunteers. To identify the most relevant features, 7 fecal metabolites and 4 microbiota were selected by random forest (RF), from A and B sample sets, respectively. Furthermore, we constructed support vector machines (SVM) classifification model using 7 fecal metabolites or 4 gut microbes, or 7 fecal metabolites with 4 gut microbes, respectively, on C sample set. The accuracy of classifification model was 0.714, 0.857, 0.857, respectively, and the AUC was 0.71, 0.88, 0.9, respectively. In C sample set, Spearman's rank correlation analysis demonstrated heptadecanoic acid and pentadecanoic acid were signifificantly negatively correlated to and , respectively. We constructed SVM classifification model using 2 correlated fecal metabolites and 2 correlated gut microbes on C sample set. The accuracy of classification model was 0.857, and the AUC was 0.88.
CONCLUSION
Therefore, heptadecanoic acid and pentadecanoic acid, crosstalk with fecal-derived gut microbiota namely Erysipelotrichaceae_UCG-003 and Haemophilus, are potential non-invasive biomarkers for CAG diagnosis.
Topics: Humans; Gastrointestinal Microbiome; Gastritis, Atrophic; RNA, Ribosomal, 16S; Feces; Biomarkers; Firmicutes
PubMed: 36699724
DOI: 10.3389/fcimb.2022.1064737