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1.
Small ; : e2400878, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39105375

ABSTRACT

Amateurs often struggle with detecting and quantifying protein biomarkers in body fluids due to the high expertise required. This study introduces a Lab-in-a-Vial (LV) rapid diagnostic platform, featuring hydrangea-like platinum nanozymes (PtNH), for rapid, accurate detection and quantification of protein biomarkers on-site within 15 min. This method significantly enhances detection sensitivity for various biomarkers in body fluids, surpassing traditional methods such as enzyme-linked immunosorbent assays (ELISA) and lateral flow assays (LFA) by ≈250 to 1300 times. The LV platform uses a glass vial coated with specific bioreceptors such as antigens or antibodies, enabling rapid in vitro evaluation of disease risk from small fluid samples, similar to a personal ELISA-like point-of-care test (POCT). It overcomes challenges in on-site biomarker detection, allowing both detection and quantification through a portable wireless spectrometer for healthcare internet of things (H-IoT). The platform's effectiveness and adaptability are confirmed using IgG/IgM antibodies from SARS-CoV-2 infected patients and nuclear matrix protein (NMP22) from urothelial carcinoma (UC) patients as biomarkers. These tests demonstrated its accuracy and flexibility. This approach offers vast potential for diverse disease applications, provided that the relevant protein biomarkers in bodily fluids are identified.

2.
Sci Total Environ ; 947: 174541, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-38977091

ABSTRACT

Polypropylene microplastics (PP-MPs) are emerging pollutant commonly detected in various environmental matrices and organisms, while their adverse effects and mechanisms are not well known. Here, zebrafish embryos were exposed to environmentally relevant concentrations of PP-MPs (0.08-50 mg/L) from 2 h post-fertilization (hpf) until 120 hpf. The results showed that the body weight was increased at 2 mg/L, heart rate was reduced at 0.08 and 10 mg/L, and behaviors were impaired at 0.4, 10 or 50 mg/L. Subsequently, transcriptomic analysis in the 0.4 and 50 mg/L PP-MPs treatment groups indicated potential inhibition on the glycolysis/gluconeogenesis and oxidative phosphorylation pathways. These findings were validated through alterations in multiple biomarkers related to glucose metabolism. Moreover, abnormal mitochondrial ultrastructures were observed in the intestine and liver in 0.4 and 50 mg/L PP-MPs treatment groups, accompanied by significant decreases in the activities of four mitochondrial electron transport chain complexes and ATP contents. Oxidative stress was also induced, as indicated by significantly increased ROS levels and significant reduced activities of CAT and SOD and GSH contents. All the results suggested that environmentally relevant concentrations of PP-MPs could induce disrupted mitochondrial energy metabolism in zebrafish, which may be associated with the observed behavioral impairments. This study will provide novel insights into PP-MPs-induced adverse effects and highlight need for further research.


Subject(s)
Energy Metabolism , Microplastics , Mitochondria , Polypropylenes , Water Pollutants, Chemical , Zebrafish , Animals , Water Pollutants, Chemical/toxicity , Energy Metabolism/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Microplastics/toxicity , Polypropylenes/toxicity , Larva/drug effects , Oxidative Stress/drug effects , Behavior, Animal/drug effects , Embryo, Nonmammalian/drug effects
4.
Pol J Microbiol ; 73(2): 217-235, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38905278

ABSTRACT

Interferon-alpha (IFN-α) is a first-line drug for treating chronic hepatitis B (CHB). Guanylate-binding protein 1 (GBP1) is one of the interferon-stimulating factors, which participates in the innate immunity of the host and plays an antiviral and antibacterial role. In this study, we explored how GBP1 is involved in IFN-α antiviral activity against HBV. Before being gathered, HepG2-NTCP and HepG2 2.15 cells were transfected with the wild-type hGBP1 plasmid or si-GBP1, respectively, and followed by stimulation with Peg-IFNα-2b. We systematically explored the role of GBP1 in regulating HBV infection in cell models. Additionally, we also examined GBP1 levels in CHB patients. GBP1 activity increased, and its half-life was prolonged after HBV infection. Overexpression of GBP1 inhibited the production of HBsAg and HBeAg, as well as HBs protein and HBV total RNA levels, whereas silencing of GBP1 inhibited its ability to block viral infections. Interestingly, overexpressing GBP1 co-treatment with Peg-IFNα-2b further increased the antiviral effect of IFN-α, while GBP1 silencing co-treatment with Peg-IFNα-2b partly restored its inhibitory effect on HBV. Mechanistically, GBP1 mediates the anti-HBV response of Peg-IFNα-2b by targeting HBs. Analysis of clinical samples revealed that GBP1 was elevated in CHB patients and increased with Peg-IFNα-2b treatment, while GBP1 showed good stability in the interferon response group. Our study demonstrates that GBP1 inhibits HBV replication and promotes HBsAg clearance. It is possible to achieve antiviral effects through the regulation of IFN-α induced immune responses in response to HBV.


Subject(s)
Antiviral Agents , GTP-Binding Proteins , Hepatitis B virus , Hepatitis B, Chronic , Interferon-alpha , Humans , Interferon-alpha/pharmacology , Interferon-alpha/immunology , Hepatitis B virus/drug effects , Hepatitis B virus/physiology , Antiviral Agents/pharmacology , GTP-Binding Proteins/genetics , GTP-Binding Proteins/metabolism , GTP-Binding Proteins/immunology , Hep G2 Cells , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/virology , Hepatitis B, Chronic/immunology , Male , Hepatitis B Surface Antigens/immunology , Hepatitis B Surface Antigens/metabolism , Female , Adult , Virus Replication/drug effects , Hepatitis B/virology , Hepatitis B/immunology , Hepatitis B/drug therapy
5.
J Phys Chem A ; 128(21): 4335-4352, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38752854

ABSTRACT

Obtaining accurate enthalpies of formation of chemical species, ΔHf, often requires empirical corrections that connect the results of quantum mechanical (QM) calculations with the experimental enthalpies of elements in their standard state. One approach is to use atomization energy corrections followed by bond additivity corrections (BACs), such as those defined by Petersson et al. or Anantharaman and Melius. Another approach is to utilize isodesmic reactions (IDRs) as shown by Buerger et al. We implement both approaches in Arkane, an open-source software that can calculate species thermochemistry using results from various QM software packages. In this work, we collect 421 reference species from the literature to derive ΔHf corrections and fit atomization energy corrections and BACs for 15 commonly used model chemistries. We find that both types of BACs yield similar accuracy, although Anantharaman- and Melius-type BACs appear to generalize better. Furthermore, BACs tend to achieve better accuracy than IDRs for commonly used model chemistries, and IDRs can be less robust because of the sensitivity to the chosen reference species and reactions. Overall, Anantharaman- and Melius-type BACs are our recommended approach for achieving accurate QM corrections for enthalpies.

6.
J Phys Chem A ; 128(14): 2891-2907, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38536892

ABSTRACT

Detailed chemical kinetic models offer valuable mechanistic insights into industrial applications. Automatic generation of reliable kinetic models requires fast and accurate radical thermochemistry estimation. Kineticists often prefer hydrogen bond increment (HBI) corrections from a closed-shell molecule to the corresponding radical for their interpretability, physical meaning, and facilitation of error cancellation as a relative quantity. Tree estimators, used due to limited data, currently rely on expert knowledge and manual construction, posing challenges in maintenance and improvement. In this work, we extend the subgraph isomorphic decision tree (SIDT) algorithm originally developed for rate estimation to estimate HBI corrections. We introduce a physics-aware splitting criterion, explore a bounded weighted uncertainty estimation method, and evaluate aleatoric uncertainty-based and model variance reduction-based prepruning methods. Moreover, we compile a data set of thermochemical parameters for 2210 radicals involving C, O, N, and H based on quantum chemical calculations from recently published works. We leverage the collected data set to train the SIDT model. Compared to existing empirical tree estimators, the SIDT model (1) offers an automatic approach to generating and extending the tree estimator for thermochemistry, (2) has better accuracy and R2, (3) provides significantly more realistic uncertainty estimates, and (4) has a tree structure much more advantageous in descent speed. Overall, the SIDT estimator marks a great leap in kinetic modeling, offering more precise, reliable, and scalable predictions for radical thermochemistry.

7.
J Cancer Res Clin Oncol ; 150(3): 158, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38530426

ABSTRACT

BACKGROUND: Although routine antiviral therapy has been implemented in HCC patients, the risk of HBV reactivation (HBVr) remains with the use of programmed cell death-1(PD-1) blockade-based combination immunotherapy and the relevant risk factors are also unclear. Therefore, we aimed to identify the incidence and risk factors of HBVr in HCC patients undergoing combination therapy of PD-1 inhibitors and angiogenesis inhibitors and concurrent first-line antivirals. METHODS: We included a total of 218 HBV-related HCC patients with first-line antivirals who received PD-1 inhibitors alone or together with angiogenesis inhibitors. According to the anti-tumor therapy modalities, patients were divided into PD-1 inhibitors monotherapy group (anti-PD-1 group) and combination therapy group (anti-PD-1 plus angiogenesis inhibitors group). The primary study endpoint was the incidence of HBVr. RESULTS: HBVr occurred in 16 (7.3%) of the 218 patients, 2 cases were found in the anti-PD-1 group and the remaining 14 cases were in the combination group. The Cox proportional hazard model identified 2 independent risk factors for HBVr: combination therapy (hazard ratio [HR], 4.608, 95%CI 1.010-21.016, P = 0.048) and hepatitis B e antigen (HBeAg) positive (HR, 3.695, 95%CI 1.246-10.957, P = 0.018). Based on the above results, we developed a simple risk-scoring system and found that the high-risk group (score = 2) developed HBVr more frequently than the low-risk group (score = 0) (Odds ratio [OR], 17.000, 95%CI 1.946-148.526, P = 0.01). The area under the ROC curve (AUC-ROC) was 7.06 (95%CI 0.581-0.831, P = 0.006). CONCLUSION: HBeAg-positive patients receiving combination therapy have a 17-fold higher risk of HBVr than HBeAg-negative patients with PD-1 inhibitors monotherapy.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis B , Liver Neoplasms , Humans , Hepatitis B virus , Hepatitis B/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Angiogenesis Inhibitors/therapeutic use , Hepatitis B e Antigens/pharmacology , Hepatitis B e Antigens/therapeutic use , Angiogenesis , Liver Neoplasms/drug therapy , Virus Activation , Antiviral Agents/therapeutic use
8.
Environ Sci Technol ; 58(11): 4937-4947, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38446036

ABSTRACT

Bis(2-ethylhexyl)-tetrabromophthalate (TBPH), a typical novel brominated flame retardant, has been ubiquitously identified in various environmental and biotic media. Consequently, there is an urgent need for precise risk assessment based on a comprehensive understanding of internal exposure and the corresponding toxic effects on specific tissues. In this study, we first investigated the toxicokinetic characteristics of TBPH in different tissues using the classical pseudo-first-order toxicokinetic model. We found that TBPH was prone to accumulate in the liver rather than in the gonad, brain, and muscle of both female and male zebrafish, highlighting a higher internal exposure risk for the liver. Furthermore, long-term exposure to TBPH at environmentally relevant concentrations led to increased visceral fat accumulation, signaling potential abnormal liver function. Hepatic transcriptome analysis predominantly implicated glycolipid metabolism pathways. However, alterations in the profile of associated genes and biochemical indicators revealed gender-specific responses following TBPH exposure. Besides, histopathological observations as well as the inflammatory response in the liver confirmed the development of nonalcoholic fatty liver disease, particularly in male zebrafish. Altogether, our findings highlight a higher internal exposure risk for the liver, enhancing our understanding of the gender-specific metabolic-disrupting potential associated with TBPH exposure.


Subject(s)
Flame Retardants , Zebrafish , Animals , Male , Female , Liver/metabolism , Lipid Metabolism , Flame Retardants/toxicity , Flame Retardants/analysis
9.
PLoS One ; 19(1): e0296689, 2024.
Article in English | MEDLINE | ID: mdl-38277380

ABSTRACT

The frozen ground robot can be widely and prospectively applied in plentiful fields, such as military rescue and planet exploration. Based on the energy-saving, load-bearing, and attachment functions of reindeer hooves, we studied the kinematics of reindeer feet and designed a biomimetic energy-saving attachment mechanical foot (mechanical foot I) and two contrast mechanical feet (mechanical feet II and III). The energy-saving and load-bearing performances of the biomimetic mechanical foot were tested on a motion mechanics platform, which revealed this mechanical foot was adaptive to three types of ground (frozen ground, ice, and water ice lunar soil). Mechanical foot I possesses the functions of elastic energy storage and power consumption reduction, and its power range is from -2.77 to -27.85 W. Compared with mechanical foot III, the load-bearing ability of mechanical foot I was improved by the dewclaws, and the peak forces in the X, Y, and Z directions increased by about 2.54, 1.25 and 1.31 times, respectively. When mechanical foot I acted with more- smooth surface, the joint range of motion (ROM) increased, changes of the three-directional force at the foot junction decreased. The forces were the lowest on ice among the three types of ground, the X-, Y- and Z-directional changes were about 62.96, 83.7, and 319.85 N respectively, and the ROMs for the ankle joint and metatarsophalangeal joint of mechanical foot I were about 17.93° and 16.10°, respectively. This study revealed the active adaptation mechanism between the biomimetic mechanical foot and ice or frozen ground, and thus theoretically underlies research on the biomimetic mechanical foot.


Subject(s)
Ice , Reindeer , Animals , Biomimetics , Foot , Ankle Joint , Weight-Bearing , Biomechanical Phenomena , Gait
10.
Cancer Imaging ; 24(1): 20, 2024 Jan 26.
Article in English | MEDLINE | ID: mdl-38279133

ABSTRACT

BACKGROUND & AIMS: The present study utilized extracted computed tomography radiomics features to classify the gross tumor volume and normal liver tissue in hepatocellular carcinoma by mainstream machine learning methods, aiming to establish an automatic classification model. METHODS: We recruited 104 pathologically confirmed hepatocellular carcinoma patients for this study. GTV and normal liver tissue samples were manually segmented into regions of interest and randomly divided into five-fold cross-validation groups. Dimensionality reduction using LASSO regression. Radiomics models were constructed via logistic regression, support vector machine (SVM), random forest, Xgboost, and Adaboost algorithms. The diagnostic efficacy, discrimination, and calibration of algorithms were verified using area under the receiver operating characteristic curve (AUC) analyses and calibration plot comparison. RESULTS: Seven screened radiomics features excelled at distinguishing the gross tumor area. The Xgboost machine learning algorithm had the best discrimination and comprehensive diagnostic performance with an AUC of 0.9975 [95% confidence interval (CI): 0.9973-0.9978] and mean MCC of 0.9369. SVM had the second best discrimination and diagnostic performance with an AUC of 0.9846 (95% CI: 0.9835- 0.9857), mean Matthews correlation coefficient (MCC)of 0.9105, and a better calibration. All other algorithms showed an excellent ability to distinguish between gross tumor area and normal liver tissue (mean AUC 0.9825, 0.9861,0.9727,0.9644 for Adaboost, random forest, logistic regression, naivem Bayes algorithm respectively). CONCLUSION: CT radiomics based on machine learning algorithms can accurately classify GTV and normal liver tissue, while the Xgboost and SVM algorithms served as the best complementary algorithms.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Bayes Theorem , Radiomics , Tumor Burden , Liver Neoplasms/diagnostic imaging , Machine Learning , Retrospective Studies
11.
Small ; 20(8): e2303871, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37817349

ABSTRACT

A syringe-based, semi-automatic environmental monitoring device is developed for on-site detection of harmful heavy metal ions in water. This portable device consists of a spring-embedded syringe and a polydimethylsiloxane (PDMS) membrane-based flow regulator for semi-automatic fix-and-release fluidic valve actuation, and a paper-based analytical device (PAD) with two kinds of gold nanoclusters (AuNCs) for sensitive Hg2+ and Co2+ ion detection, respectively. The thickness of the elastic PDMS membrane can be adjusted to stabilize and modulate the flow rates generated by the pushing force provided by the spring attached to the plunger. Also, different spring constants can drastically alter the response time. People of all ages can extract the fix-volume sample solutions and then release them to automatically complete the detection process, ensuring high reliability and repeatability. The PAD comprises two layers of modified paper, and each layer is immobilized with bovine serum albumin-capped gold nanoclusters (R-AuNCs) and glutathione-capped gold clusters (G-AuNCs), respectively. The ligands functionalized on the surface of the AuNCs not only can fine-tune the optical properties of the nanoclusters but also enable specific and simultaneous detection of Hg2+ and Co2+ ions via metallophilic Au+ -Hg2+ interaction and the Co2+ -thiol complexation effect, respectively. The feasibility of the device for detecting heavy metal ions at low concentrations in various environmental water samples is demonstrated. The Hg2+ and Co2+ ions can be seen simultaneously within 20 min with detection limits as low as 1.76 nm and 0.27 µm, respectively, lower than those of the regulatory restrictions on water by the US Environmental Protection Agency and the European Union. we expect this sensitive, selective, portable, and easy-to-use device to be valid for on-site multiple heavy metal ion pollution screenings in resource-constrained settings.

12.
J Appl Clin Med Phys ; 25(1): e14218, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38013656

ABSTRACT

OBJECTIVE: This study aimed to discuss the dosimetric advantages of helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT) technology in hippocampal avoidance whole-brain radiotherapy and provide references for clinical selection of ideal radiotherapy technology. METHODS: A total of 20 patients with hippocampal avoidance whole-brain radiotherapy were chosen randomly. Computed tomography (CT) and MRI scanning images were input into the treatment planning system (TPS). After the CT and enhanced magnetic resonance T1 weighted images were fused and registered, the same radiation therapy physician was invited to outline the tumor target volume. PTV-HS refers to the whole brain subtracted by 5 mm outward expansion of the hippocampus (HP). The prescribed dose was 30 Gy/10 fractions. HT and VMAT plans were designed for each patient in accordance with PTV. Under the premise that the 95% isodose curve covers the PTV, dose-volume histogram was applied to evaluate the PTV, conformal index (CI), heterogeneity index (HI), maximum dose (Dmax), mean dose (Dmean), minimum dose (Dmin) and absorbed doses of organs at risk (OARs) in HT and VMAT plans. Paired t-test was performed to compare the differences between two radiation therapy plans, and p  <  0.05 was considered statistically significant. RESULTS: These two plans had no significant difference in PTV-HS (max, min, and mean). However, the HI and CI of the HT plan were significantly better than those of the VMAT plan, showing statistically significant difference (p < 0.05). The HT plan was significantly superior to the VMAT plan in terms of the Dmax, Dmin, and Dmean of HP, left and right eye lens, left and right eye, and spinal cord, showing statistically significant difference (p < 0.05). The HT plan was also better than the VMAT plan in terms of the Dmax of the left optic nerve. However, the two plans showed no obvious differences in terms of the absorbed doses of the right optic nerve and brainstem, without statistical significance. CONCLUSIONS: Compared with the VMAT plan of hippocampal avoidance, HT technology has significant dosimetric advantages. HT plans significantly decreased the radiation dose and radiation volume of OARs surrounding the target area (e.g., surrounding eye lens and eye, especially hippocampal avoidance area) while increasing the CI and HI of PTV dose in whole brain radiotherapy (WBRT) greatly, thus enabling the decrease in the incidence rate of radioactive nerve function impairment.


Subject(s)
Radiotherapy, Intensity-Modulated , Humans , Radiotherapy, Intensity-Modulated/methods , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted/methods , Organs at Risk , Brain , Hippocampus
13.
Adv Healthc Mater ; 13(5): e2302927, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37986024

ABSTRACT

The global pandemic presents a critical threat to humanity, with no effective rapid-response solutions for early-stage virus dissemination. This study aims to create an AI-driven entry-blocker design system (AIEB) to fabricate inhalable virus-like nanocatchers (VLNCs) fused with entry-blocking peptides (EBPs) to counter pandemic viruses and explore therapeutic applications. This work focuses on developing angiotensin-converting enzyme 2 (ACE2)-mimic domain-fused VLNCs (ACE2@VLNCs) using AIEB and analyzing their interaction with the SARS-CoV-2 receptor binding domain (RBD), demonstrating their potential to hinder SARS-CoV-2 infection. Aerosol-based tests show ACE2@VLNCs persist over 70 min in the air and neutralize pseudoviruses within 30 min, indicating their utility in reducing airborne virus transmission. In vivo results reveal ACE2@VLNCs mitigate over 67% of SARS-CoV-2 infections. Biosafety studies confirm their safety, causing no damage to eyes, skin, lungs, or trachea, and not eliciting significant immune responses. These findings offer crucial insights into pandemic virus prevention and treatment, highlighting the potential of the ACE2@VLNCs system as a promising strategy against future pandemics.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Humans , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , SARS-CoV-2/physiology , Peptides/metabolism , Artificial Intelligence , Protein Binding
14.
J Agric Food Chem ; 72(1): 540-548, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38131295

ABSTRACT

Gibberellins (GAs) are plant hormones widely used in agriculture. At present, GAs are produced by fermentation of the fungus Fusarium fujikuroi. However, fungal growth is too slow, resulting in slow fungal fermentation and a low yield. Here, to develop an alternative production source of GAs, an artificial pathway was engineered in Escherichia coli. By selecting and combining enzymes derived from plants and bacteria, a novel 4-enzyme pathway was successfully constructed to produce GAs using steviol, a readily available and less valuable byproduct during enzymatic refining of rebaudioside A, as a feedstock. Whole-cell biotransformation with E. coli strain expressing the novel pathway produced 71.17 ± 2.00 mg/L GA1 and a trace amount of GA3 from steviol in 48 h. This report presents a significant advancement in the fast production of GAs and establishes a method for the metabolism of terpenoids to produce target products in microbial hosts.


Subject(s)
Diterpenes, Kaurane , Gibberellins , Gibberellins/metabolism , Escherichia coli/genetics , Escherichia coli/metabolism , Plant Growth Regulators
15.
Materials (Basel) ; 16(22)2023 Nov 17.
Article in English | MEDLINE | ID: mdl-38005139

ABSTRACT

This work reports new mixed matrix membranes (MMMs) for the adsorption of enzymes from organic solvents. In this work, polyimide/hydroxyapatite (PI/HAP) MMMs were prepared via phase inversion method and further crosslinked with 3-aminopropyl triethoxysilane (APTES). The chemical and structural stability of the crosslinked PI/HAP MMMs were improved and applied for lysozyme (LZ) adsorption in organic solvent. PI/HAP MMMs were crosslinked by changing the 3-aminopropyltriethoxysilane (APTES) concentration and crosslinking time. The optimal APTES crosslinking condition for PI/HAP MMMs is 6% of concentration for 8 h. The LZ adsorption performance was studied by changing solvent types. PI/HAP MMMs possessed a high LZ adsorption in organic-solvent-aqueous solutions, and the LZ adsorption capacity reached 34.1 mg/g. The MMMs had a high desorption capacity and recovery ability. The MMMs maintained 60% of their adsorption capacity and 58% of their desorption at the fourth cycle of adsorption and desorption. The MMMs provided a new technology for the purification and separation of enzymes or proteins by MMMs in organic solvents.

17.
Appl Opt ; 62(22): 5867, 2023 Aug 01.
Article in English | MEDLINE | ID: mdl-37706935

ABSTRACT

This publisher's note amends the author listing of Appl. Opt.60, 10885 (2021)APOPAI0003-693510.1364/AO.434229.

18.
Food Funct ; 14(17): 7780-7798, 2023 Aug 29.
Article in English | MEDLINE | ID: mdl-37575049

ABSTRACT

Gut inflammation seriously affects the healthy life of patients, and has a trend of increasing incidence rate. However, the current methods for treating gut inflammation are limited to surgery and drugs, which can cause irreversible damage to patients, especially infants. As natural oligosaccharides in human breast milk, human milk oligosaccharides (HMOs) function as probiotics in treating and preventing gut inflammation: improving the abundance of the gut microbiota, increasing the gut barrier function, and reducing the gut inflammatory reaction. Meanwhile, due to the complexity and high cost of their synthesis, people are searching for functional oligosaccharides that can replace HMOs as a food additive in infants milk powder and adjuvant therapy for chronic inflammation. The purpose of this review is to summarize the therapeutic and preventive effects of HMOs and their substitute functional oligosaccharides as probiotics in gut inflammation, and to summarize the prospect of their application in infant breast milk replacement in the future.


Subject(s)
Gastrointestinal Microbiome , Probiotics , Infant , Female , Humans , Milk, Human , Oligosaccharides/pharmacology , Probiotics/therapeutic use , Health Status
19.
Mol Immunol ; 160: 95-102, 2023 08.
Article in English | MEDLINE | ID: mdl-37413911

ABSTRACT

Despite the wide usage of ß2-adrenoceptor agonists in asthma treatment, they do have side effects such as aggravating inflammation. We previously reported that isoprenaline induced Cl- secretion and IL-6 release via cAMP-dependent pathways in human bronchial epithelia, but the mechanisms underlying the inflammation-aggravation effects of ß2-adrenoceptor agonists remain pooly understood. In this study, we investigated formoterol, a more specific ß2-adrenoceptor agonist, -mediated signaling pathways involved in the production of IL-6 and IL-8 in 16HBE14o- human bronchial epithelia. The effects of formoterol were detected in the presence of PKA, exchange protein directly activated by cAMP (EPAC), cystic fibrosis transmembrane conductance regulator (CFTR), extracellular signal-regulated protein kinase (ERK)1/2 and Src inhibitors. The involvement of ß-arrestin2 was determined using siRNA knockdown. Our results indicate that formoterol can induce IL-6 and IL-8 secretion in concentration-dependent manner. The PKA-specific inhibitor, H89, partially inhibited IL-6 release, but not IL-8. Another intracellular cAMP receptor, EPAC, was not involved in either IL-6 or IL-8 release. PD98059 and U0126, two ERK1/2 inhibitors, blocked IL-8 while attenuated IL-6 secretion induced by formoterol. Furthermore, formoterol-induced IL-6 and IL-8 release was attenuated by Src inhibitors, namely dasatinib and PP1, and CFTRinh172, a CFTR inhibitor. In addition, knockdown of ß-arrestin2 by siRNA only suppressed IL-8 release when a high concentration of formoterol (1 µM) was used. Taken together, our results suggest that formoterol stimulates IL-6 and IL-8 release which involves PKA/Src/ERK1/2 and/or ß-arrestin2 signaling pathways.


Subject(s)
Cystic Fibrosis Transmembrane Conductance Regulator , Interleukin-8 , Humans , Formoterol Fumarate/pharmacology , Cystic Fibrosis Transmembrane Conductance Regulator/metabolism , Interleukin-8/metabolism , Interleukin-6/metabolism , Guanine Nucleotide Exchange Factors/metabolism , Inflammation , RNA, Small Interfering , Receptors, Adrenergic/metabolism
20.
Molecules ; 28(13)2023 Jun 25.
Article in English | MEDLINE | ID: mdl-37446646

ABSTRACT

Cordyceps exopolysaccharide (CEP) has shown emerging potential in adjustment of gut microbiota and immune cell function. In this study, a water-soluble CEP with a molecular weight of 58.14 kDa was extracted from the fermentation broth of Paecilomyces hepiali, an endophytic fungus of Cordyceps sinensis. Our results indicated that Paecilomyces hepiali polysaccharide (PHP) showed significantly preventive potential on dextran sulfate sodium (DSS)-induced colitis in mice, which can prevent colon shortening, reduce intestinal epithelial cell (IEC) destruction, suppress inflammatory cell infiltration, and regulate the balance between regulatory T (Treg) cells and T helper type 17 (Th17) cells. Meanwhile, the disturbed gut microbiota was partially restored after PHP treatment. Further Pearson correlation coefficient analyses exhibited that the alteration of the gut microbiota was significantly related to adjustment of the IEC barrier and Treg/Th17 balance. In conclusion, all findings proposed that purified PHP has the potential to develop into a promising agent for colitis prevention and adjuvant therapy via maintaining intestinal homeostasis of gut microbiota and immune system.


Subject(s)
Colitis, Ulcerative , Colitis , Gastrointestinal Microbiome , Animals , Mice , T-Lymphocytes, Regulatory , Colitis/chemically induced , Colitis/drug therapy , Colon/metabolism , Polysaccharides/pharmacology , Polysaccharides/metabolism , Dextran Sulfate/toxicity , Disease Models, Animal , Mice, Inbred C57BL , Colitis, Ulcerative/chemically induced
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