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1.
Nat Prod Res ; : 1-8, 2024 Jul 07.
Article in English | MEDLINE | ID: mdl-38972057

ABSTRACT

Rhynchostylis retusa (L.) Blume, commonly known as the Foxtail orchid, has garnered worldwide attention for its diverse medicinal properties. In this study, root extract and its fractions were evaluated for total polyphenols, flavonoids, targeted polyphenols, and antioxidant potential. The antimicrobial activity was assessed against Gram-positive and Gram-negative bacterial strains while cytotoxicity was assessed using the A549 and HCT-116 cell lines. The investigations showed that chloroform and ethyl acetate are the most effective solvents for fractionation of polyphenols from the parent extract. These fractions also exhibited strong antioxidant and cytotoxic potentials. The chloroform fraction showed maximum cell death of 87.35 and 92.36% in A549 and HCT- 116 cell lines respectively. All samples showed growth inhibition against bacterial strains except the n-hexane fraction, whereas the n-butanol fraction showed comparable antimicrobial activity with the tetracycline standard. The possible health benefits and thereby, application of R. retusa were thus revealed in this investigation.

2.
Cureus ; 16(6): e61926, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38978893

ABSTRACT

Patent ductus arteriosus (PDA) is one of the most prevalent acyanotic congenital heart diseases. Percutaneous closure of PDA has been the preferred treatment recommended by the guidelines due to relatively low complications and rapid patient recovery. However, device emboli remain the most frequent and disastrous complication, necessitating percutaneous or surgical treatment. We present a case of a large PDA closure in pulmonary arterial hypertension paediatric patients complicated with device emboli that was successfully retrieved using the snaring technique. Transcatheter retrieval, although technically challenging, is a feasible treatment and offers the advantage of avoiding the need for surgical intervention.

3.
Food Chem ; 458: 140291, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38959795

ABSTRACT

Staphylococcus aureus contamination continues to be a harmful foodborne pathogen threatening of human health, and there is a growing need for rapid detection technologies. This study proposed a novel paper biosensor based on a polydiacetylene (PDA) polymer functionalized fibrinogen (Fg) for the detection of S. aureus in food sources. The fluorophore was developed based on the high binding ability of fibrinogen-binding proteins on the surface of S. aureus. This binding caused twisting in the PDA backbone, leading to changes in chromatic and fluorescent. The detection limit of this method was 50.1 CFU/mL for S. aureus-contaminated foodstuffs and 65.0 CFU/mL for the pure S. aureus culture, and the novelty came from its rapidity and selectivity for S. aureus compared to other foodborne bacteria. In summary, the present work provides a rapid detection method for S. aureus detection, which will help in addressing food safety-related issues.

4.
Pediatr Cardiol ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38953954

ABSTRACT

Ductal stenting (DS) is an alternative to the Blalock-Taussig-Thomas Shunt (BTTS) as initial palliation for congenital heart disease with duct-dependent pulmonary blood flow (DDBPF). We sought to analyze the impact of intended single ventricle (SV) and biventricular (BiV) repair pathways on the outcome of DS and BTTS in infants with DDPBF. A single-center, retrospective comparison of infants with DDPBF who underwent either DS (2012-2022) or BTTS procedures (2013-2017). Primary outcomes included all-cause mortality and risk of unplanned re-intervention. Participants were divided into four groups: 1.SV with DS, 2.SV with BTTS, 3.BiV with DS, and 4.BiV with BTTS. Fifty-one DS (SV 45%) and 86 BTTS (SV 49%) procedures were undertaken. For those who had DS, mortality was lower in the BiV compared to SV patients (BiV: 0/28, versus SV: 4/23, p = 0.04). Compared to BiV DS, BiV BTTS had a higher risk of combined death or unplanned re-intervention (HR 4.28; CI 1.25-14.60; p = 0.02). In SV participants, there was no difference for either primary outcome based on procedure type. DS was associated with shorter intensive care length of stay for SV participants (mean difference 5 days, p = 0.01) and shorter intensive care and hospital stay for BiV participants (mean difference 11 days for both outcomes, p = 0.001). There is a survival benefit for DS in BiV participants compared with DS in SV and BTTS in BiV participants. Ductal stenting is associated with a shorter intensive care and hospital length of stay.

5.
Echocardiography ; 41(8): e15890, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39043208

ABSTRACT

PURPOSE: Left atrium to aortic root ratio (LA/Ao) is an echocardiographic marker of hemodynamically significant patent ductus arteriosus (PDA). Since 2-dimensional measurement of the ratio is geometrically limited, left atrial volume (LAV) which has 3-dimensional characteristics was investigated. The aim of this study was to determine a correlation between LA/Ao ratio and LAV as well as holodiastolic flow reversal in preterm neonates with and without a PDA. METHODS: A retrospective evaluation of neonates with and without PDA was performed. Targeted neonatal echocardiography evaluation of LA/Ao and LAV was measured from parasternal long-axis view and the apical 4 and 2-chamber views, respectively. Univariate and linear regression analysis were performed. RESULTS: 200 patients were included of whom 158 (79.0%) had a PDA shunt. The median gestational age at the time of echo was 27.4 weeks (IQR: 25.7-29.4 weeks). The median LA/Ao ratio was 1.51 (IQR: 1.26-1.83) and median LAV indexed to weight was  .91 mL/kg (IQR: .65-1.18 mL/kg). There was a significant correlation between LA/Ao and LAV indexed to weight in the PDA group (r2 = .080, p = .0003). LA/Ao ratio and LAV indexed to weight differed significantly between those with diastolic flow reversal versus no-flow reversal (LA/Ao, p = .003; LAV, p = .001). CONCLUSIONS: This study demonstrated a significant correlation between LA/Ao and LAV in preterm infants with PDA, with greater magnitude of discordance for LAV. The power of LAV versus LA/Ao in monitoring hemodynamically significant PDA requires prospective evaluation.


Subject(s)
Ductus Arteriosus, Patent , Echocardiography , Heart Atria , Infant, Premature , Humans , Ductus Arteriosus, Patent/physiopathology , Ductus Arteriosus, Patent/diagnostic imaging , Infant, Newborn , Female , Male , Retrospective Studies , Heart Atria/diagnostic imaging , Heart Atria/physiopathology , Echocardiography/methods , Aorta/diagnostic imaging , Aorta/physiopathology
6.
J Cardiovasc Dev Dis ; 11(7)2024 Jun 28.
Article in English | MEDLINE | ID: mdl-39057619

ABSTRACT

Persistent Patent Ductus Arteriosus (PDA) is prevalent among extremely preterm infants, with its occurrence inversely related to gestational age. A persistent PDA correlates with increased mortality and morbidities such as intraventricular hemorrhage, pulmonary hemorrhage, chronic lung disease, bronchopulmonary dysplasia, and necrotizing enterocolitis as observed clinically. Conversely, numerous randomized controlled trials have failed to demonstrate significant benefits from PDA treatment. One contributing factor to these conflicting findings is that PDA affects each individual differently depending on the cardiovascular decompensation and its hemodynamic impact. PDA management should be based on the hemodynamic significance, rather than just the presence or size of PDA. This comprehensive narrative review paper describes echocardiographic parameters that allow a better understanding of the hemodynamic impact of PDA. A newer modality, like lung ultrasound, is also described here as an adjunct to assess the PDA impact on the lungs from pulmonary overcirculation.

7.
Expert Opin Pharmacother ; : 1-10, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39041726

ABSTRACT

INTRODUCTION: Bronchopulmonary dysplasia (BPD) is the commonest adverse outcome of extremely prematurely born infants, and its incidence is increasing. Affected infants suffer chronic respiratory morbidity and are at risk of early onset of chronic obstructive pulmonary disease. It is, therefore, important that these infants are appropriately managed, with efficacious pharmacological treatments. AREAS COVERED: Searches were made on Embase, PubMed, and the Cochrane database for ('treatment' or 'drug therapy/') and ('bronchopulmonary dysplasia' or 'chronic lung disease') and ('neonatology' or 'newborn' or 'prematurity' or 'baby') between 2019 and 2024. Corticosteroids, diuretics, caffeine, anti-asthmatics, nutritional supplements, and medications treating patent ductus arteriosus and pulmonary hypertension are discussed. EXPERT OPINION: Dexamethasone is associated with adverse neurodevelopmental outcomes and impairment of adult lung function. Inhaled corticosteroids have not resulted in significant effects on BPD. Diuretics only result in short-term improvements in lung function and have side-effects. Evidence suggests it is better to wait and see than aggressively treat PDA; inhaled nitric oxide and sildenafil can improve oxygenation, but whether they improve long-term outcomes remains to be tested. Stem cells are a promising therapy, but further research is required. Appropriately designed trials are required to identify efficacious treatments for infants with BPD.

8.
Radiol Case Rep ; 19(9): 3805-3809, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39006093

ABSTRACT

A 27-year-old woman developed a cough, shortness of breath, and symptoms mimicking pregnancy complications 6 days after childbirth. Unilateral pulmonary artery agenesis (UAPA), a rare congenital condition, was diagnosed through a chest CT scan. This case highlights the variable presentation of UAPA, even in adults, and the challenges of diagnosis during the postpartum period. Early diagnosis and management are critical for improving pregnancy outcomes in women with UAPA.

9.
Anal Chim Acta ; 1317: 342920, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39030014

ABSTRACT

BACKGROUND: As a broad-spectrum tetracycline antibiotic, Oxytetracycline (OTC) was widely used in a variety of applications. But, the overuse of OTC had led to the detection of it in food, water and soil, which could present significance risk to human health and cause damage to ecosystem. It was of great significance to develop sensitive detection methods for OTC. Herein, an environmentally friendly photoelectrochemical (PEC) aptasensor was constructed for the sensitive detection of OTC based on CuO-induced BiOBr/Ag2S/PDA (Polydopamine) photocurrent polarity reversal. RESULTS: BiOBr/Ag2S/PDA composites modified electrode not only produced stable initial anodic photocurrent but also provided attachment sites for the aptamer S1 of OTC by the strong adhesion of PDA. On the other hand, CuO loaded OTC aptamer S2 (Cu-S2) was got through Cu-S bonds. After the target OTC was identified on the electrode surface, CuO was introduced to the surface of ITO/BiOBr/Ag2S/PDA through the specific binding of OTC to S2. This identification process formed dual Z-type heterojunctions and resulted in a remarkable reversal of photocurrent polarity from anodic to cathodic. Under optimization conditions, the PEC aptasensor showed a wide linear range (50 fM âˆ¼ 100 nM), low detection limit (1.9 fM), excellent selectivity, stability and reproducibility for the detection of OTC. Moreover, it was successfully used for the analysis of OTC in real samples of tap water, milk and honey, and had the potential for practical application. SIGNIFICANCE: This work developed an environmentally friendly photocurrent-polarity-switching PEC aptasensor with excellent selectivity, reproducibility, stability, low LOD and wide linear range for OTC detection. This sensitive system, which was including BiOBr, Ag2S, PDA and CuO were low toxicity, not only reduced the risk of traditional toxic semiconductors to operators and the environment, but can also be used for the detection of real samples, broadening the wider range of applications for BiOBr, Ag2S, PDA and CuO.


Subject(s)
Aptamers, Nucleotide , Biosensing Techniques , Bismuth , Copper , Electrochemical Techniques , Oxytetracycline , Oxytetracycline/analysis , Copper/chemistry , Aptamers, Nucleotide/chemistry , Electrochemical Techniques/methods , Bismuth/chemistry , Photochemical Processes , Silver Compounds/chemistry , Polymers/chemistry , Electrodes , Animals , Limit of Detection , Indoles/chemistry , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/chemistry
10.
Molecules ; 29(13)2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38999046

ABSTRACT

Sea buckthorn and Japanese knotweed are known in many traditional medicine systems to be a great source of bioactive substances. This research aims to compare the bioactivity and protective effects of the phenolic extracts of leaves from sea buckthorn and roots and leaves from the Japanese knotweed on erythrocytes. The polyphenol composition of the extract was analyzed using UPLC-PDA-ESI-MS/MS. The extracts' toxicity and impact on the erythrocytes' osmotic fragility were measured spectrophotometrically. The antioxidant activity was determined based on the inhibition of oxidation of erythrocytes and their membrane induced by 2,2'-Azobis(2-methylpropionamidine) dihydrochloride (AAPH),measured spectrophotometrically and using fluorimetry. To find the possible mechanism of the extracts' action, extract-modified cells were observed under a microscope, and the potential localization of the extract's phytochemical composition was checked using fluorescent probes. The results showed that the used extracts are not toxic to erythrocytes, increase their osmotic resistance, and successfully protect them against free radicals. Extract components localize on the outer part of the membrane, where they can scavenge the free radicals from the environment. Altogether, the presented extracts can greatly protect living organisms against free radicals and can be used to support the treatment of diseases caused by excess free radicals.


Subject(s)
Erythrocyte Membrane , Hippophae , Plant Extracts , Polyphenols , Hippophae/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Polyphenols/pharmacology , Polyphenols/chemistry , Erythrocyte Membrane/drug effects , Antioxidants/pharmacology , Antioxidants/chemistry , Plant Leaves/chemistry , Animals , Protective Agents/pharmacology , Protective Agents/chemistry , Erythrocytes/drug effects , Erythrocytes/metabolism , Osmotic Fragility/drug effects
11.
ACS Appl Mater Interfaces ; 16(31): 40739-40752, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39047081

ABSTRACT

Oxidative stress (OS) is a major mediator of secondary brain injury following intracerebral hemorrhage (ICH). Thus, antioxidant therapy is emerging as an attractive strategy to combat ICH. To achieve both reactive oxygen species (ROS) scavenging ability and on-demand drug release ability, we constructed a novel polydopamine (PDA)-coated diselenide-bridged mesoporous silica nanoparticle (DSeMSN) drug delivery system (PDA-DSeMSN). Edaravone (Eda) was blocked in the pores of DSeMSN by covering the pores with PDA as a gatekeeper. The drug maintained nearly "zero release" before reaching the lesion site, while in the ROS-enriched circumstances, the PDA shell went through degradation and the doped diselenide bonds broke up, triggering the disintegration of nanoparticles and leading to Eda release. Interestingly, the ROS-degradable property of the PDA shell and diselenide bond endowed the system with enhanced ROS-eliminating capacity. The synergistic effect of ROS-responsive drug delivery and ROS-scavenging PDA-DSeMSN showed efficient antioxidative and mitochondria protective performance without apparent toxicity in vitro. Importantly, PDA-DSeMSN@Eda through intravenous administration specifically accumulated in perihematomal sites and demonstrated robust neuroprotection in an ICH mouse model through antioxidative and antiapoptotic effects with high biological safety. Thus, the PDA-DSeMSN platform holds tremendous potential as an excellent carrier for on-demand delivery of drugs and provides a new and effective strategy for the clinical treatment of ICH.


Subject(s)
Cerebral Hemorrhage , Edaravone , Indoles , Nanoparticles , Reactive Oxygen Species , Silicon Dioxide , Animals , Silicon Dioxide/chemistry , Cerebral Hemorrhage/drug therapy , Cerebral Hemorrhage/pathology , Reactive Oxygen Species/metabolism , Mice , Nanoparticles/chemistry , Edaravone/chemistry , Edaravone/pharmacology , Indoles/chemistry , Indoles/pharmacology , Porosity , Polymers/chemistry , Polymers/pharmacology , Free Radical Scavengers/chemistry , Free Radical Scavengers/pharmacology , Male , Antioxidants/chemistry , Antioxidants/pharmacology , Oxidative Stress/drug effects
12.
Zhongguo Zhong Yao Za Zhi ; 49(11): 2965-2972, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-39041156

ABSTRACT

This study developed a UPLC-PDA wavelength switching method to simultaneously determine the content of maltol and seventeen saponins in red and black ginseng and compared the quality differences of two different processed products of red and black ginseng. A Waters HSS T3 column(2. 1 mm×100 mm, 1. 8 µm) at 30 ℃ was adopted, with the mobile phase of acetonitrile(A) and water containing 0. 1% phosphoric acid(B) under gradient elution, the flow rate of 0. 3 m L·min~(-1), and the injection volume of 2 µL.The wavelength switching was set at 273 nm within 0-11 min and 203 nm within 11-60 min. The content results of multiple batches of red and black ginseng samples were analyzed by the hierarchical cluster analysis(HCA) and principal component analysis(PCA) to evaluate the quality difference. The results showed that the 18 constituents exhibited good linear relationships within certain concentration ranges, with the correlation coefficients(r) greater than 0. 999 1. The relative standard deviations(RSDs) of precision,repeatability, and stability were all less than 5. 0%. The average recoveries ranged from 95. 93% to 104. 2%, with an RSD of 1. 8%-4. 2%. The content determination results showed that the quality of red and black ginseng samples was different, and the two types of processed products were intuitively distinguished by HCA and PCA. The method is accurate, reliable, and reproducible. It can be used to determine the content of maltol and seventeen saponins in red and black ginseng and provide basic information for the quality evaluation and comprehensive utilization of red and black ginseng.


Subject(s)
Panax , Pyrones , Saponins , Panax/chemistry , Saponins/analysis , Saponins/chemistry , Chromatography, High Pressure Liquid/methods , Pyrones/analysis , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/analysis
13.
Cureus ; 16(6): e63177, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39070397

ABSTRACT

Agenesis of corpus callosum (ACC) is a congenital absence of corpus callosum either completely or partially; without deficits in behavior or function during the first two years of life. Patent ductus arteriosus (PDA) is a congenital cardiac defect in which there is persistent contact between the pulmonary artery and the descending thoracic aorta due to failure of the normal physiologic closure of the fetal ductus. This article details a unique case of a three-month-old male infant who was initially diagnosed with PDA and later discovered to have corpus callosum agenesis. The child was posted on a PDA device for closure. Here, we will be discussing syndromic association, difficult airway, procedure-related factors, and pediatric anesthesia management of this rare case.

14.
Eur J Pediatr ; 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39073470

ABSTRACT

Moderate-to-large patent ductus arteriosus (PDA) has been linked to increased risk of bronchopulmonary dysplasia (BPD), while lung ultrasound score (LUS) has been demonstrated to accurately predict BPD. We aimed to investigate the correlation of LUS as a marker of interstitial pulmonary edema and the severity of the ductal shunt in predicting future BPD development in very preterm infants. This secondary analysis of a prospective study recruited preterm infants with gestational age < 30 weeks. LUS on postnatal days 7 and 14, and echocardiographic data [PDA diameter and left atrium-to-aortic root ratio (LA/Ao)] near LUS acquisition were collected. Correlation coefficient, logistics regression analysis, and the area under the receiver operating characteristic (AUROC) procedure were used. A statistically significant and positive correlation existed between LUS and PDA diameter (ρ = 0.415, ρ = 0.581, and p < 0.001) and LA/Ao (ρ = 0.502, ρ = 0.743, and p < 0.001) at postnatal days 7 and 14, respectively, and the correlations of LUS and echocardiographic data were generally stronger in the non-BPD group. In the prediction of BPD, LUS incorporating echocardiographic data at postnatal days 7 obtained significantly higher predictive performance compared to LUS alone (AUROC 0.878 [95% CI 0.801-0.932] vs. AUROC 0.793 [95% CI 0.706-0.865]; Delong test, p = 0.013). CONCLUSIONS: There is a statistically significant correlation between LUS and echocardiographic data, suggesting their potential role as early predictors for respiratory outcomes in very preterm infants. WHAT IS KNOWN: • Lung ultrasound score (LUS) has shown good reliability in predicting bronchopulmonary dysplasia (BPD) development. • Some echocardiographic data that characterized ventricular function was reported to be used to predict severe BPD. WHAT IS NEW: • There is a positive and statistically significant correlation between LUS and echocardiographic data at postnatal days 7 and 14. • The integrated use of LUS and echocardiographic data may have potential value in predicting BPD.

15.
J Mass Spectrom ; 59(7): e5045, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38837562

ABSTRACT

Soybean is scientifically known as Glycine max. It belongs to the Fabaceae family. It consists of a lot of bioactive phytochemicals like saponin, phenolic acid, flavonoid, sphingolipids and phytosterols. It also owns excellent immune-active effects in the physiological system. Soy and its phytochemicals have been found to have pharmacological properties that include anticancer, antioxidant, anti-hypercholesterolaemic, anti-diabetic, oestrogenic, anti-hyperlipidaemic, anti-inflammatory, anti-obesity, anti-hypertensive, anti-mutagenic, immunomodulatory, anti-osteoporotic, antiviral, hepatoprotective, antimicrobial, goitrogenic anti-skin ageing, wound healing, neuroprotective and anti-photoageing activities. Present study has been designed to set standard pharmacognostical extraction method, complexation of compounds, qualitative evaluation through phytochemical screening, identification by TLC, physicochemical properties, solubility profile, total phenolic, flavonoid content as well as analytical evaluation or characterisation like UV and FT-IR of methanolic extract of G. max. The final observations like physicochemical properties such as total ash value, LOD and pH were recorded. Phytochemical screenings show the presence of flavonoid, alkaloid, saponin, carbohydrate, tannins, protein, gums and mucilage, fixed oils and fats. The results were found significant. Further in silico studies proved creatinine and euparin to be potent wound healing agents.


Subject(s)
Flavonoids , Glycine max , Phytochemicals , Plant Extracts , Seeds , Tandem Mass Spectrometry , Wound Healing , Wound Healing/drug effects , Plant Extracts/chemistry , Plant Extracts/pharmacology , Tandem Mass Spectrometry/methods , Seeds/chemistry , Glycine max/chemistry , Phytochemicals/analysis , Phytochemicals/chemistry , Phytochemicals/pharmacology , Flavonoids/analysis , Flavonoids/chemistry , Flavonoids/pharmacology , Methanol/chemistry , Computer Simulation , Phenols/analysis , Phenols/chemistry , Phenols/pharmacology , Animals
16.
Interv Cardiol Clin ; 13(3): 355-368, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38839169

ABSTRACT

Transcatheter ductal closure has proven to be safe and effective to occlude the patent ductus arteriosus (PDA) in premature infants. We have developed a robust multidisciplinary PDA program. After gaining experience performing transcatheter ductal closure in the cardiac catheterization laboratory, we transitioned to performing the procedure at the patient's bedside in the neonatal intensive care unit using echocardiographic guidance. The bedside approach has the potential to expand this therapy to patients who currently undergo expectant PDA management because of lack of availability of this therapy, and allow for earlier referral, which will reduce time of exposure to this pathologic shunt.


Subject(s)
Cardiac Catheterization , Ductus Arteriosus, Patent , Infant, Premature , Humans , Ductus Arteriosus, Patent/surgery , Ductus Arteriosus, Patent/diagnosis , Infant, Newborn , Cardiac Catheterization/methods , Septal Occluder Device , Echocardiography/methods
18.
Interv Cardiol Clin ; 13(3): 421-430, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38839174

ABSTRACT

Since PDA stenting was first attempted in the early 1990s, significant technical advancements have improved outcomes and some centers have even transitioned to exclusive PDA stenting for all infants with duct-dependent pulmonary circulation. In addition to its use in infants with duct-dependent pulmonary circulation, PDA stenting has also been adapted as a percutaneous palliative option for suprasystemic pulmonary arterial hypertension and as a component of the hybrid procedure. In this article, the authors aim to review indications and outcomes for PDA stenting, describe the procedure, and discuss future directions.


Subject(s)
Ductus Arteriosus, Patent , Stents , Humans , Ductus Arteriosus, Patent/surgery , Cardiac Catheterization/methods , Palliative Care/methods , Treatment Outcome
19.
Int J Mol Sci ; 25(12)2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38928326

ABSTRACT

Diagnostic markers are desperately needed for the early detection of pancreatic ductal adenocarcinoma (PDA). We describe sets of markers expressed in temporal order in mouse models during pancreatitis, PDA initiation and progression. Cell type specificity and the differential expression of PDA markers were identified by screening single cell (sc) RNAseq from tumor samples of a mouse model for PDA (KIC) at early and late stages of PDA progression compared to that of a normal pancreas. Candidate genes were identified from three sources: (1) an unsupervised screening of the genes preferentially expressed in mouse PDA tumors; (2) signaling pathways that drive PDA, including the Ras pathway, calcium signaling, and known cancer genes, or genes encoding proteins that were identified by differential mass spectrometry (MS) of mouse tumors and conditioned media from human cancer cell lines; and (3) genes whose expression is associated with poor or better prognoses (PAAD, oncolnc.org). The developmental progression of PDA was detected in the temporal order of gene expression in the cancer cells of the KIC mice. The earliest diagnostic markers were expressed in epithelial cancer cells in early-stage, but not late-stage, PDA tumors. Other early markers were expressed in the epithelium of both early- and late-state PDA tumors. Markers that were expressed somewhat later were first elevated in the epithelial cancer cells of the late-stage tumors, then in both epithelial and mesenchymal cells, or only in mesenchymal cells. Stromal markers were differentially expressed in early- and/or late-stage PDA neoplasia in fibroblast and hematopoietic cells (lymphocytes and/or macrophages) or broadly expressed in cancer and many stromal cell types. Pancreatitis is a risk factor for PDA in humans. Mouse models of pancreatitis, including caerulein treatment and the acinar-specific homozygous deletion of differentiation transcription factors (dTFs), were screened for the early expression of all PDA markers identified in the KIC neoplasia. Prognostic markers associated with a more rapid decline were identified and showed differential and cell-type-specific expression in PDA, predominately in late-stage epithelial and/or mesenchymal cancer cells. Select markers were validated by immunohistochemistry in mouse and human samples of a normal pancreas and those with early- and late-stage PDA. In total, we present 2165 individual diagnostic and prognostic markers for disease progression to be tested in humans from pancreatitis to late-stage PDA.


Subject(s)
Biomarkers, Tumor , Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Pancreatitis , Animals , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/metabolism , Carcinoma, Pancreatic Ductal/diagnosis , Carcinoma, Pancreatic Ductal/pathology , Pancreatitis/metabolism , Pancreatitis/genetics , Pancreatitis/pathology , Pancreatitis/diagnosis , Mice , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/pathology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Humans , Prognosis , Gene Expression Regulation, Neoplastic , Disease Models, Animal , Cell Line, Tumor , Disease Progression
20.
Molecules ; 29(11)2024 May 24.
Article in English | MEDLINE | ID: mdl-38893365

ABSTRACT

The use of z-drugs has increased worldwide since its introduction. Although the prescribing patterns of hypnotics differ among countries, zolpidem is the most widely used z-drug in the world. Zolpidem may be involved in poisoning and deaths. A simple and fast HPLC-PDA method was developed and validated. Zolpidem and the internal standard chloramphenicol were extracted from plasma using a sonication-assisted dispersive liquid-liquid microextraction procedure. The method was validated including selectivity, linearity, precision, accuracy, and recovery. The calibration range (0.15-0.6 µg/mL) covers therapeutic and toxic levels of zolpidem in plasma. The limit of quantification was set at 0.15 µg/mL. Intra- and interday accuracy and precision values were lower than 15% at the concentration levels studied. Excellent recovery results were obtained for all concentrations. The proposed method was successfully applied to ten real postmortem plasma samples. In our series, multiple substances (alcohol and/or other drugs) were detected in most cases of death involving zolpidem. Our analytical method is suitable for routine toxicological analysis.


Subject(s)
Liquid Phase Microextraction , Zolpidem , Zolpidem/blood , Humans , Liquid Phase Microextraction/methods , Chromatography, High Pressure Liquid/methods , Sonication/methods , Reproducibility of Results , Hypnotics and Sedatives/blood , Limit of Detection , Pyridines/blood
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