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1.
J Endocrinol Invest ; 2024 Oct 09.
Article in English | MEDLINE | ID: mdl-39382628

ABSTRACT

BACKGROUND: The adrenocortical carcinoma (ACC) is a rare and highly aggressive malignancy originating from the adrenal cortex. These patients usually undergo chemotherapy with etoposide, doxorubicin, cisplatin and mitotane (EDP-M) in case of locally advanced or metastatic ACC. Computed tomography (CT) radiomics showed to be useful in adrenal pathologies. The study aimed to analyze the association between response to EDP-M treatment and CT textural features at diagnosis in patients with locally advanced or metastatic ACCs. METHODS: We enrolled 17 patients with advanced or metastatic ACC who underwent CT before and after EDP-M therapy. The response to treatment was evaluated according to RECIST 1.1, Choi, and volumetric criteria. Based on the aforementioned criteria, the patients were classified as responders and not responders. Textural features were extracted from the biggest lesion in contrast-enhanced CT images with LifeX software. ROC curves were drawn for the variables that were significantly different (p < 0.05) between the two groups. RESULTS: Long-run high grey level emphasis (LRHGLE_GLRLM) and histogram kurtosis were significantly different between responder and not responder groups (p = 0.04) and the multivariate ROC curve combining the two features showed a very good AUC (0.900; 95%IC: 0.724-1.000) in discriminating responders from not responders. More heterogeneous tissue texture of initial staging CT in locally advanced or metastatic ACC could predict the positive response to EDP-M treatment. CONCLUSIONS: Adrenal texture is able to predict the response to EDP-M therapy in patients with advanced ACC.

3.
Front Microbiol ; 15: 1396064, 2024.
Article in English | MEDLINE | ID: mdl-39314875

ABSTRACT

The effects of climate change are becoming increasingly hazardous for our ecosystem. Climate resilient landscaping, which promotes the use of native plants, has the potential to simultaneously decrease the rate of climate change, enhance climate resilience, and combat biodiversity losses. Native plants and their associated microbiome form a holo-organism; interaction between plants and microbes is responsible for plants' growth and proper functioning. In this study, we were interested in exploring the soil and root microbiome composition associated with Shepherdia utahensis, a drought hardy plant proposed for low water use landscaping, which is the hybrid between two native hardy shrubs of Utah, S. rotudifolia and S. argentea. The bulk soil, rhizosphere, root, and nodule samples of the hybrid Shepherdia plants were collected from three locations in Utah: the Logan Campus, the Greenville farm, and the Kaysville farm. The microbial diversity analysis was conducted, and plant growth-promoting bacteria were isolated and characterized from the rhizosphere. The results suggest no difference in alpha diversity between the locations; however, the beta diversity analysis suggests the bacterial community composition of bulk soil and nodule samples are different between the locations. The taxonomic classification suggests Proteobacteria and Actinobacteriota are the dominant species in bulk soil and rhizosphere, and Actinobacteriota is solely found in root and nodule samples. However, the composition of the bacterial community was different among the locations. There was a great diversity in the genus composition in bulk soil and rhizosphere samples among the locations; however, Frankia was the dominant genus in root and nodule samples. Fifty-nine different bacteria were isolated from the rhizosphere and tested for seven plant growth-promoting (PGP) traits, such as the ability to fix nitrogen, phosphates solubilization, protease activity, siderophore, Indole Acetic Acid (IAA) and catalase production, and ability to use ACC as nitrogen source. All the isolates produced some amount of IAA. Thirty-one showed at least four PGP traits and belonged to Stenotrophomonas, Chryseobacterium, Massilia, Variovorax, and Pseudomonas. We shortlisted 10 isolates that showed all seven PGP traits and will be tested for plant growth promotion.

4.
Int J Mol Sci ; 25(18)2024 Sep 22.
Article in English | MEDLINE | ID: mdl-39337655

ABSTRACT

We have previously shown that the overexpression of acetyl-CoA carboxylase 1 (ACC1) was associated with the poor prognosis of cholangiocarcinoma (CCA) patients, and suppression of its expression in CCA cell lines deteriorated cell growth. The present study explored the mechanism by which ACC1 inhibition affects global protein acetylation, using genetic knockdown and pharmacological inhibition with an ACC1 inhibitor ND-646 as models. Both ACC1 knockdown and ACC1-inhibitor-treated cells displayed the hyperacetylation of proteins, accompanied by impaired growth and migration. The immunoprecipitation of hyperacetylated proteins using the anti-acetylated lysine antibody, followed by tandem mass spectrometry, identified three potential verification candidates, namely POTE ankyrin domain family member E, peroxisomal biogenesis factor 1, and heat shock protein 90 beta (HSP90B). HSP90 acetylation was the candidate selected for the verification of protein acetylation. To establish the effects of protein hyperacetylation, treatment with suberoylanilide hydroxamic acid (SAHA), a lysine deacetylase inhibitor, was conducted, and this served as an independent model. Decreased tumor growth but increased acetylated protein levels were observed in ACC1-KD xenograft tumors. Hyperacetylated-alleviated cell growth and migration were consistently observed in the SAHA-treated models. The molecular linkage between protein hyperacetylation and the AKT/GSK3ß/Snail pathway was demonstrated. This study highlighted the importance of protein acetylation in CCA progression, suggesting that ACC1 and KDAC are potential targets for CCA treatment.


Subject(s)
Acetyl-CoA Carboxylase , Bile Duct Neoplasms , Cell Movement , Cell Proliferation , Cholangiocarcinoma , Cholangiocarcinoma/metabolism , Cholangiocarcinoma/pathology , Cholangiocarcinoma/genetics , Acetylation , Humans , Animals , Cell Line, Tumor , Bile Duct Neoplasms/metabolism , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/genetics , Mice , Acetyl-CoA Carboxylase/metabolism , HSP90 Heat-Shock Proteins/metabolism , Mice, Nude , Xenograft Model Antitumor Assays
5.
Egypt Heart J ; 76(1): 127, 2024 Sep 14.
Article in English | MEDLINE | ID: mdl-39276199

ABSTRACT

BACKGROUND: This systematic review aims to determine the impact of isolated diastolic hypertension (IDH) on cardiovascular outcomes. METHODS: We searched only English language articles on PubMed and SCOPUS until July 31, 2023 to investigate the association between IDH and cardiovascular outcomes. RESULTS: This meta-analysis of 19 studies evaluated the impact of different hypertension diagnostic guidelines (ACC/AHA: American Heart Association/American College of Cardiology; JNC7: Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; NICE/ESC: National Institute for Health and Care Excellence/European Society of Cardiology) on hypertension-related outcomes. Studies had varying sample sizes (173 to 2,969,679 participants) and study designs. In cohort studies using JNC7 guidelines, IDH was linked to increased cardiovascular disease (CVD) risk (HR: 1.45, 95% CI 1.17, 1.74), CVD mortality (HR: 1.54, 95% CI 1.23, 1.84), and coronary heart disease (CHD) risk (HR: 1.65). In studies using ACC/AHA guidelines, associations with CVD risk and CVD mortality were weaker [HR: 1.16 (95% CI 1.06, 1.25) and 1.10 (95% CI 0.95, 1.25), respectively]. Subgroup analysis revealed differences in outcomes on the basis of age and sex. Cross-sectional studies did not show significant associations with JNC7 and ACC guidelines; NICE guidelines were not used in cross-sectional studies. CONCLUSION: IDH is associated with an increased risk of CVD. Higher diastolic blood pressure cutoffs were associated with higher cardiovascular risk. This association varied by study design and effect modification by sex and race influenced the association.

6.
Adv Exp Med Biol ; 1460: 539-574, 2024.
Article in English | MEDLINE | ID: mdl-39287864

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is in parallel with the obesity epidemic, and it is the most common cause of liver diseases. The patients with severe insulin-resistant diabetes having high body mass index (BMI), high-grade adipose tissue insulin resistance, and high hepatocellular triacylglycerols (triglycerides; TAG) content develop hepatic fibrosis within a 5-year follow-up. Insulin resistance with the deficiency of insulin receptor substrate-2 (IRS-2)-associated phosphatidylinositol 3-kinase (PI3K) activity causes an increase in intracellular fatty acid-derived metabolites such as diacylglycerol (DAG), fatty acyl CoA, or ceramides. Lipotoxicity-related mechanism of NAFLD could be explained still best by the "double-hit" hypothesis. Insulin resistance is the major mechanism in the development and progression of NAFLD/nonalcoholic steatohepatitis (NASH). Metabolic oxidative stress, autophagy, and inflammation induce NASH progression. In the "first hit" the hepatic concentrations of diacylglycerol increase with an increase in saturated liver fat content in human NAFLD. Activities of mitochondrial respiratory chain complexes are decreased in the liver tissue of patients with NASH. Hepatocyte lipoapoptosis is a critical feature of NASH. In the "second hit," reduced glutathione levels due to oxidative stress lead to the overactivation of c-Jun N-terminal kinase (JNK)/c-Jun signaling that induces cell death in the steatotic liver. Accumulation of toxic levels of reactive oxygen species (ROS) is caused at least by two ineffectual cyclical pathways. First is the endoplasmic reticulum (ER) oxidoreductin (Ero1)-protein disulfide isomerase oxidation cycle through the downstream of the inner membrane mitochondrial oxidative metabolism and the second is the Kelch like-ECH-associated protein 1 (Keap1)-nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathways. In clinical practice, on ultrasonographic examination, the elevation of transaminases, γ-glutamyltransferase, and the aspartate transaminase to platelet ratio index indicates NAFLD. Fibrosis-4 index, NAFLD fibrosis score, and cytokeratin18 are used for grading steatosis, staging fibrosis, and discriminating the NASH from simple steatosis, respectively. In addition to ultrasonography, "controlled attenuation parameter," "magnetic resonance imaging proton-density fat fraction," "ultrasound-based elastography," "magnetic resonance elastography," "acoustic radiation force impulse elastography imaging," "two-dimensional shear-wave elastography with supersonic imagine," and "vibration-controlled transient elastography" are recommended as combined tests with serum markers in the clinical evaluation of NAFLD. However, to confirm the diagnosis of NAFLD, a liver biopsy is the gold standard. Insulin resistance-associated hyperinsulinemia directly accelerates fibrogenesis during NAFLD development. Although hepatocyte lipoapoptosis is a key driving force of fibrosis progression, hepatic stellate cells and extracellular matrix cells are major fibrogenic effectors. Thereby, these are pharmacological targets of therapies in developing hepatic fibrosis. Nonpharmacological management of NAFLD mainly consists of two alternatives: lifestyle modification and metabolic surgery. Many pharmacological agents that are thought to be effective in the treatment of NAFLD have been tried, but due to lack of ability to attenuate NAFLD, or adverse effects during the phase trials, the vast majority could not be licensed.


Subject(s)
Liver Cirrhosis , Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/metabolism , Liver Cirrhosis/pathology , Liver Cirrhosis/metabolism , Insulin Resistance , Liver/pathology , Liver/metabolism , Disease Progression , Oxidative Stress , Severity of Illness Index , Animals
7.
Neuropsychologia ; 204: 109003, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39293637

ABSTRACT

Due to the similarities in behavioral characteristics between romantic love and addictive disorders, the concept of being "addicted to someone" transcends mere literary metaphor, expanding perspectives on the study of romantic love and inspiring interventions for addiction. However, there has been a lack of studies systematically exploring the similarities and differences between romantic love and addiction at the neural level. In this study, we conducted an extensive literature search, incorporating 21 studies on romantic love and 28 on addictive disorders, focusing on fMRI research utilizing the cue reactivity paradigm. Using Activation Likelihood Estimation, we examined the similarities and differences in the neural mechanisms underlying love and addiction. The results showed that the anterior cingulate cortex (ACC) exhibited both shared and distinct activation clusters between romantic love and addictive disorders. Furthermore, ventromedial prefrontal cortex (VMPFC) was more frequently activated in romantic love than in addictive disorders, while greater activation within the posterior cingulate cortex (PCC) was found in addictive disorder compared with romantic love. We discussed that the activation of ACC and VMPFC may symbolize self-expansion, a process that characterizes the development of romantic love, contributing to a more enriched self. Our study suggests that while romantic love and addictive disorders share a common neural foundation, the discernible differences in their neural representations distinguish them as joyful growth versus compulsive hedonism.

8.
Sci Rep ; 14(1): 22368, 2024 09 27.
Article in English | MEDLINE | ID: mdl-39333140

ABSTRACT

Pulse rate (PR) and respiratory rate (RR) are two of the most important vital signs. Monitoring them would benefit from easy-to-use technologies. Hence, wearable devices would, in principle, be ideal candidates for such systems. The neck, although highly susceptible to artifacts, presents an attractive location for a diverse pool of physiological biomarkers monitoring purposes such as airflow sensing in a non-obstructive manner. This paper presents a methodology for PR and RR estimation using photoplethysmography (PPG) and accelerometry (Acc) sensors placed on the neck. Neck PPG and Acc signals were recorded from 22 healthy participants for RR estimation, where the resting subjects performed guided breathing following a visual metronome. Neck PPG signals were obtained from 16 healthy participants who breathed through an altitude generator machine in order to acquire a wider range of PR readings while at rest. The proposed methodology was able to provide rate estimates via a combination of recursive FFT-based dominance scoring coupled with an exponentially weighted moving average (EWMA)-driven aggregation scheme. The recursion aimed at bypassing sudden intra-window amplitude deviations caused by momentary artifacts, while the EWMA-based aggregation was utilized for handling inter-window artifact-induced deviations. To further improve estimation stability and confidence, estimates were calculated in the form of rate bands taking into account the relevant clinically acceptable error margins, and results when considering rate values and rate bands are presented and discussed. The framework was able to achieve an overall pulse rate value accuracy of 93.67 ± 7.64 % within the clinically acceptable ± 5 BPM with reference to the gold-standard reference devices while providing an overall respiratory rate value accuracy within the clinically appropriate ± 3 BrPM of 94.94 ± 3.56 % with reference to the guiding visual metronome, and 88.4 ± 7.63 % with respect to the gold-standard reference device. The proposed methodology achieves acceptable PR and RR estimation capabilities, even when signals are acquired from an unusual location such as the neck. This work introduces novel ideas that can lead to the development of medical device outputs for PR and RR monitoring, especially capitalizing on the advantages of the neck as a multi-modal physiological monitoring location.


Subject(s)
Neck , Photoplethysmography , Respiratory Rate , Signal Processing, Computer-Assisted , Wearable Electronic Devices , Humans , Photoplethysmography/methods , Photoplethysmography/instrumentation , Neck/physiology , Male , Female , Adult , Vital Signs , Heart Rate/physiology , Accelerometry/instrumentation , Accelerometry/methods , Young Adult , Monitoring, Physiologic/methods , Monitoring, Physiologic/instrumentation , Algorithms
9.
3 Biotech ; 14(10): 229, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39268413

ABSTRACT

This study looked at the possibility of using bacteria that were separated from the rhizosphere of rice plants to promote plant development and offer biological control against pests that affect agriculture. A total of 119 bacteria were isolated from rice rhizospheres collected from six different locations. Of these, 15.47% showed phosphate solubilization, 47.05% showed IAA, 89.07% showed siderophore, and 10.08% showed ACC deaminase activity. Generally, high siderophore production was observed in strains showing ACC deaminase activity. The antagonistic behavior of all strains against the walnut pest Xanthomonas arbiricola was also studied, and eight (6.7%) isolates suppressed the growth of this pathogen (7-43 ± 2 mm zone diameter). It was also noted that these eight isolates showed almost exclusively siderophore activity. In contrast to IAA and siderophore synthesis, the study demonstrated reduced activity levels for phosphate solubilization and ACC deaminase. The 16S rRNA sequence results of some of the bacteria selected in this study and AFLP analysis based on some restriction enzymes showed that the diversity was quite high. According to the 16S rRNA analysis, the high antagonistic effect of strain 71, which is one of the members of the Enterobacter genus, shows that it can be used as a biocontrol agent. In this study, it was revealed in detail that bacteria can be preferred as alternative biological agents for plant growth instead of synthetic fertilizers. This is the first study on this subject in this region, which is one of the important points of the country in terms of rice production. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04077-5.

10.
Plant J ; 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39222478

ABSTRACT

Plant hormones are chemical signals governing almost every aspect of a plant's life cycle and responses to environmental cues. They are enmeshed within complex signaling networks that can only be deciphered by using broad-scale analytical methods to capture information about several plant hormone classes simultaneously. Methods used for this purpose are all based on reversed-phase (RP) liquid chromatography and mass spectrometric detection. Hydrophilic interaction chromatography (HILIC) is an alternative chromatographic method that performs well in analyses of biological samples. We therefore developed and validated a HILIC method for broad-scale plant hormone analysis including a rapid sample preparation procedure; moreover, derivatization or fractionation is not required. The method enables plant hormone screening focused on polar and moderately polar analytes including cytokinins, auxins, jasmonates, abscisic acid and its metabolites, salicylates, indoleamines (melatonin), and 1-aminocyclopropane-1-carboxylic acid (ACC), for a total of 45 analytes. Importantly, the major pitfalls of ACC analysis have been addressed. Furthermore, HILIC provides orthogonal selectivity to conventional RP methods and displays greater sensitivity, resulting in lower limits of quantification. However, it is less robust, so procedures to increase its reproducibility were established. The method's potential is demonstrated in a case study by employing an approach combining hormonal analysis with phenomics to examine responses of three Arabidopsis ecotypes toward three abiotic stress treatments: salinity, low nutrient availability, and their combination. The case study showcases the value of the simultaneous determination of several plant hormone classes coupled with phenomics data when unraveling processes involving complex cross-talk under diverse plant-environment interactions.

11.
Cureus ; 16(8): e67691, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39318899

ABSTRACT

Primary tracheal tumors are rare, with adenoid cystic carcinoma (ACC) of the trachea being the second most common malignancy of the trachea. Radical surgical resection is found to have better survival outcomes in tracheal ACC. However, with higher submucosal spread rates in tracheal ACC and the inability to achieve clear margins, complete resection is not usually achievable. In these cases, the use of a 60-70 Gy radiation dose is deemed to be sufficient for definitive treatment with or without concurrent chemotherapy. We report a case of an unresectable ACC treated with online daily adaptive cone beam computed tomography (CBCT) radiotherapy on Ethos™ (Varian Medical Systems, Palo Alto, CA). She was planned to receive 59.4 Gy in 33 fractions in two phases. For daily treatment delivery, the patient was set up on the couch using the surface-guided radiotherapy (SGRT) system of AlignRT™ (Vision RT Ltd., London, UK) and translated to the treatment isocenter. A CBCT scan was acquired, followed by rigid registration with the planning scan and PET CT. Organs at risk (OAR) and primary targets were auto-generated by the AI in a two-step process, reviewed, and edited by the radiation oncologist. Adapted and scheduled plans were compared regarding planning target volume (PTV) coverage and dose to OAR. Better PTV coverage was seen in 26 of 33 fractions with the adapted plan. On the days with lesser coverage, adapted plans demonstrated improvement in the hotspot reduction and reduction in hard dose constraints of the esophagus and lungs. Hence, adapted plans were selected for all treatment days. Our results highlight the superior target coverage and improved OAR-sparing plans in daily online adaptive radiotherapy (o-ART) compared to image-guided radiotherapy (IGRT) plans. The system's ability to adapt to daily anatomical changes, improved target coverage, and better sparing of OARs make it an encouraging option for malignancies requiring motion management.

12.
J Am Coll Cardiol ; 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39320289

ABSTRACT

AIM: The "2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery" provides recommendations to guide clinicians in the perioperative cardiovascular evaluation and management of adult patients undergoing noncardiac surgery. METHODS: A comprehensive literature search was conducted from August 2022 to March 2023 to identify clinical studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. STRUCTURE: Recommendations from the "2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery" have been updated with new evidence consolidated to guide clinicians; clinicians should be advised this guideline supersedes the previously published 2014 guideline. In addition, evidence-based management strategies, including pharmacological therapies, perioperative monitoring, and devices, for cardiovascular disease and associated medical conditions, have been developed.

13.
Curr Probl Cardiol ; 49(12): 102869, 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39343052

ABSTRACT

BACKGROUND: The criteria for ASD closure in patients with PAH are different between the AHA/ACC and the ESC guidelines. We aimed to study the prevalence of patients with different guideline criteria for ASD closure and its impact on the clinical outcome after closure. METHODS AND RESULTS: A retrospective cohort study recruiting patients who underwent ASD closure from 2011-2020 was conducted in a single university hospital. Patients were grouped into ASD closure recommended (class I, class IIa, and class IIb) and ASD closure not recommended groups (class III). The primary outcome was the prevalence of patients with discordant criteria and the clinical outcomes and echocardiographic parameters after ASD closure. A total of 17 of 66 ASD patients (25.8 %) were diagnosed with ASD with pulmonary hypertension. Two patients were excluded due to incomplete right heart catheterization data. 13 patients (86.7 %) were classified as ASD-closure recommended group by both guidelines. Two patients, classified as class IIb by ACC/AHA guidelines, were unsuitable for ASD closure by ESC guidelines. After ASD closure, all 15 patients reported functional class improvement and no significant difference in the echocardiography parameters. However, the number of patients with a low probability of PHT was higher in patients with ESC guideline-recommended closure. CONCLUSIONS: Most patients (86.7 %) are in concordant classification regarding ASD closure recommendations. The ESC guidelines are more restrictive than the AHA/ACC guidelines, allowing fewer patients for ASD closure. However, the clinical outcomes after ASD closure are not significantly different between these guidelines.

14.
J Plast Reconstr Aesthet Surg ; 98: 1-9, 2024 Aug 17.
Article in English | MEDLINE | ID: mdl-39213903

ABSTRACT

BACKGROUND: Dexmedetomidine (Dex) as a local anesthesia adjuvant for nerve block procedures can improve the quality of patient recovery. However, the impact of using Dex as a local anesthetic adjuvant for serratus anterior plane block (SAPB) procedures on recovery quality for children undergoing ear reconstruction remains unclear. METHODS: Eighty-four patients who underwent ear reconstruction with autogenous costal cartilage (ACC) were randomized into two groups (n = 42/group) in which SAPB was performed with ropivacaine alone (R group) and with Dex and ropivacaine (DR group). Primary outcomes were patient 15-item quality of recovery (QoR-15) scale scores on days 1 and 2 post-surgery. Secondary outcomes included postoperative rest and coughing numerical rating scale (NRS) chest pain scores, duration of analgesia, oral rescue analgesic usage, and opioid-related side effects. RESULTS: Forty patients per group completed the study. QoR-15 scores on days 1 and 2 post-surgery in the DR group were significantly increased relative to the R group (126.35 ± 9.81 vs. 115.53 ± 8.58 and 131.78 ± 8.67 vs. 122.80 ± 8.59, all P < 0.001). Rest and coughing NRS chest pain scores at 2, 4, 8, 12, and 24 h postoperatively in the DR group were all significantly lower relative to the R group (all P < 0.05). The DR group also exhibited significantly longer analgesic duration (P < 0.001) and significantly reduced incidences of oral rescue analgesic usage and opioid-related side effect (all P < 0.05). CONCLUSION: Combining Dex and ropivacaine for SAPB in children undergoing ear reconstruction with ACC can significantly improve the quality of recovery, quality of analgesia, and analgesic duration.

15.
Cells ; 13(16)2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39195229

ABSTRACT

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) constitute an appealing tool for drug discovery, disease modeling, and cardiotoxicity screening. However, their physiological immaturity, resembling CMs in the late fetal stage, limits their utility. Herein, we have developed a novel, scalable cell culture medium designed to enhance the maturation of hPSC-CMs. This medium facilitates a metabolic shift towards fatty acid utilization and augments mitochondrial function by targeting Acetyl-CoA carboxylase 2 (ACC2) with a specific small molecule inhibitor. Our findings demonstrate that this maturation protocol significantly advances the metabolic, structural, molecular and functional maturity of hPSC-CMs at various stages of differentiation. Furthermore, it enables the creation of cardiac microtissues with superior structural integrity and contractile properties. Notably, hPSC-CMs cultured in this optimized maturation medium display increased accuracy in modeling a hypertrophic cardiac phenotype following acute endothelin-1 induction and show a strong correlation between in vitro and in vivo target engagement in drug screening efforts. This approach holds promise for improving the utility and translatability of hPSC-CMs in cardiac disease modeling and drug discovery.


Subject(s)
Acetyl-CoA Carboxylase , Cell Differentiation , Myocytes, Cardiac , Pluripotent Stem Cells , Humans , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/cytology , Acetyl-CoA Carboxylase/metabolism , Acetyl-CoA Carboxylase/antagonists & inhibitors , Pluripotent Stem Cells/drug effects , Pluripotent Stem Cells/metabolism , Pluripotent Stem Cells/cytology , Cell Differentiation/drug effects , Culture Media/pharmacology , Enzyme Inhibitors/pharmacology , Animals
17.
Int J Mol Sci ; 25(16)2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39201370

ABSTRACT

The aim of the study was to evaluate the diagnostic and prognostic significance of leptin receptor isoforms in adrenal tumors. In a single-center study, 96 patients (19 with adrenal cortical carcinoma and 77 with benign tumors) underwent an adrenalectomy. A total of 14 unaffected adrenal gland tissues from kidney donors were used as controls. Fasting blood samples were collected for laboratory tests, and mRNA expressions of leptin receptor isoforms were assessed by RT-qPCR. The study analyzed correlations between mRNA expressions and clinical data and measured NCI-H295R cell proliferation via a real-time cell analyzer. All adrenal lesions expressed leptin receptor isoforms. Significantly lower LepR1 expression was observed in carcinoma tissues than in adenomas and controls (p = 0.016). Expressions of LepR3&LepR6 were correlated with overall survival (p = 0.036), while LepR2&LepR4 and LepR5 expressions were inversely related to morning serum cortisol levels (p = 0.041). Leptin reduced NCI-H295R cell proliferation (p < 0.0001). The study highlights the diagnostic and prognostic significance of leptin receptor isoforms in adrenal tumors. Specifically, LepR1 may serve as a diagnostic marker for carcinomas, while LepR3&LepR6 have potential use as prognostic markers.


Subject(s)
Adrenal Gland Neoplasms , Receptors, Leptin , Humans , Receptors, Leptin/metabolism , Receptors, Leptin/genetics , Female , Middle Aged , Male , Adrenal Gland Neoplasms/genetics , Adrenal Gland Neoplasms/metabolism , Adrenal Gland Neoplasms/pathology , Adrenal Gland Neoplasms/blood , Prognosis , Aged , Protein Isoforms/genetics , Protein Isoforms/metabolism , Adult , Cell Proliferation , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Leptin/metabolism , Leptin/genetics , Leptin/blood , Adrenalectomy
18.
J Am Coll Cardiol ; 84(12): 1123-1143, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39127953

ABSTRACT

This document describes performance measures for heart failure that are appropriate for public reporting or pay-for-performance programs and is meant to serve as a focused update of the "2020 ACC/AHA Clinical Performance and Quality Measures for Adults With Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Performance Measures." The new performance measures are taken from the "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines" and are selected from the strongest recommendations (Class 1 or Class 3). In contrast, quality measures may not have as much evidence base and generally comprise metrics that might be useful for clinicians and health care organizations for quality improvement but are not yet appropriate for public reporting or pay-for-performance programs. New performance measures include optimal blood pressure control in patients with heart failure with preserved ejection fraction, the use of sodium-glucose cotransporter-2 inhibitors for patients with heart failure with reduced ejection fraction, and the use of guideline-directed medical therapy in hospitalized patients. New quality measures include the use of sodium-glucose cotransporter-2 inhibitors in patients with heart failure with mildly reduced and preserved ejection fraction, the optimization of guideline-directed medical therapy prior to intervention for chronic secondary severe mitral regurgitation, continuation of guideline-directed medical therapy for patients with heart failure with improved ejection fraction, identifying both known risks for cardiovascular disease and social determinants of health, patient-centered counseling regarding contraception and pregnancy risks for individuals with cardiomyopathy, and the need for a monoclonal protein screen to exclude light chain amyloidosis when interpreting a bone scintigraphy scan assessing for transthyretin cardiac amyloidosis.


Subject(s)
American Heart Association , Cardiology , Heart Failure , Humans , Heart Failure/therapy , United States , Cardiology/standards , Adult
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