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1.
Updates Surg ; 2024 Sep 05.
Article de Anglais | MEDLINE | ID: mdl-39235694

RÉSUMÉ

Worldwide use of robotic-assisted hepatectomy has increased dramatically over the past two decades. The role of robotic liver surgery is still controversial, especially with respect to its long-term oncological outcomes in treating early-stage hepatocellular carcinoma (HCC). The Glissonean approach is a fundamental technique for anatomical resection using open and laparoscopic liver surgery. To our knowledge, there have been few reports on purely robotic anatomical segmentectomy 7 for HCC using the Glissonean approach have been described. The present study describes the technical details and surgical outcomes of totally robotic segmentectomy 7 using the Glissonean approach. Fourteen patients with HCC limited to segment 7 underwent segmentectomy 7 from January 2019 through April 2023 in our hospital. The surgical techniques, peri-operative, and oncological outcomes were analyzed. Purely robotic anatomical segmentectomy 7 using the Glissonean approach was safe and feasible with the technology described herein in all of the 14 patients. The peri-operative and oncological outcomes were better and/or comparable with those of other similar hepatic resections using open approach and/or laparoscopic approach. The median follow-up time was 18 months. Intrahepatic recurrence occurred in 2 (14.3%) patient within one year following surgery. The 3-year overall survival rate was 81%. Although technically challenging, the purely robotic segmentectomy 7 could be performed safely and simultaneously with oncological radicality using the Glissonean approach.

2.
Colloids Surf B Biointerfaces ; 244: 114184, 2024 Aug 28.
Article de Anglais | MEDLINE | ID: mdl-39214032

RÉSUMÉ

Human health is under growing threat from the increasing incidence of bacterial infections. Through their antimicrobial mechanisms, bacteria use appropriate strategies to overcome the antimicrobial effects of antibiotics. The enhanced effects of synergistic strategies on drug-resistant bacteria and biofilms have led to increasing interest in these approaches in recent years. Herein, biomimetic hydroxyethyl cellulose @ Prussian blue microparticles (HEC@PB MPs) generated by the gas-shearing method show a synergistic antibacterial property induced by antibiotic-, photothermal- and photodynamic- effect. MPs, as tri-modality antibacterial agents, exhibit ideal antibacterial activity and biofilm removal effect, and their mode of action on bacteria was investigated. Additionally, a drug release concept encouraged by the ROS-driven breakdown of cellulose, as seen in brown-rot fungi, was introduced. It combines ROS-responsive HEC and photodynamic PB and is likely to fit a niche in many applications.

3.
J Sep Sci ; 47(17): e2400385, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-39215582

RÉSUMÉ

Owing to its ability to separate substances with a broad scope of polarities, exploring the three-phase solvent systems (TPSSs) with high-speed countercurrent chromatography is a topic of interest in separation science, and their retention volumes should be more concerned. This study primarily investigates the behavior of retention volumes while examining the isolation abilities of the TPSS in the technique above. We took standard compounds, including sophoricoside, Sudan red 7B, and rotenone, which have a broad range of polarity, for investigation in this study and separated them using different four-liquid TPSSs made up of water, acetonitrile, methyl acetate, and n-hexane (WAMH). Our findings show that the retention volumes gradually alter in response to changes in phase polarity within the proposed solvent systems. With TPSSs, we preliminarily studied compound isolation and the promising formula of their retention volumes. The proposed solvent systems WAMH in different ratios showed high correlations and adjusted correlation coefficients above 0.9978 and 0.9913 for the actual and calculated retention volumes. This study will be particularly beneficial for researchers focusing on countercurrent chromatography with TPSSs, as it offers valuable time-saving insights.


Sujet(s)
Distribution à contre-courant , Solvants , Solvants/composition chimique , Hexanes/composition chimique , Acétonitriles/composition chimique , Composés azoïques/composition chimique , Eau/composition chimique
4.
Phytochem Anal ; 2024 Aug 26.
Article de Anglais | MEDLINE | ID: mdl-39187395

RÉSUMÉ

INTRODUCTION: Astragaloside IV (AS-IV) is an index for the quality evaluation of the traditional Chinese medicine Astragalus and an important material basis for Astragalus to exert its medicinal effects, and it is difficult to obtain a single AS-IV by ordinary separation methods. OBJECTIVE: To find a new isolation method that can prepare AS-IV quickly and efficiently. METHODOLOGY: AS-IV was isolated from Astragalus membranaceus extract by high-speed countercurrent chromatography using a two-phase solvent system consisting of ethyl acetate/n-butanol/water (4.2:0.8:5, v/v) at a speed of 950 rpm at a flow rate of 2 mL/min using one of the high-speed countercurrent chromatographic sequential injection models developed during the previous study. RESULTS: Compared with the common countercurrent chromatographic separation, this separation method increased the injection volume and yield by 4-fold and 4.47-fold, respectively, with only about 1.2-fold increase in solvent consumption and separation time, and the purity was basically not reduced, and 55.9 mg of AS-IV, with a purity of 96.95%, was finally prepared from 400 mg of the crude extract in 240 min. CONCLUSION: The continuous injection mode of high-speed countercurrent chromatography was able to successfully prepare a large amount of AS-IV with high purity at one time.

5.
Article de Anglais | MEDLINE | ID: mdl-39169663

RÉSUMÉ

BACKGROUND AND AIMS: Extracorporeal shock wave lithotripsy for pancreatic stones (P-ESWL) and endoscopic retrograde cholangiopancreatography (ERCP) are the preferred therapeutic approaches for painful chronic pancreatitis (CP) with pancreatic stones. This study aimed to report the short- and long-term outcomes following P-ESWL and ERCP in a large cohort with CP. METHODS: Patients with painful CP and pancreatic stones >5 mm in size, who underwent P-ESWL and subsequent ERCP between March 2011 and June 2018, were included in this retrospective-prospective mixed observational study. The total stone clearance rates were recorded. All patients were followed up until the end of March 2024, with the visual analogue scale (VAS) for pain, pain type, quality-of-life scores and other relevant information recorded. RESULTS: A total of 2071 patients underwent P-ESWL, and 93.1% of them subsequently underwent ERCP during the study period. Patients were followed up for an average of 11.8 years from the onset of CP and 6.7 years from the first P-ESWL procedure. Complete stone clearance was achieved in 73.7% of the patients. At the end of the follow-up period, 70.1% of the patients achieved complete pain remission. Significant pain type conversion and lower VAS scores were observed in the patients after treatment. Quality-of-life scores and body mass indices increased after P-ESWL and ERCP. CONCLUSIONS: P-ESWL and ERCP are effective and minimally invasive treatments for pancreatic stones in patients with painful CP. Most patients achieved complete pain relief, and pain-type conversion was common after treatment. (ClinicalTrials.gov: NCT05916547).

6.
Cell Death Dis ; 15(8): 606, 2024 Aug 21.
Article de Anglais | MEDLINE | ID: mdl-39168979

RÉSUMÉ

Lymphocyte decline, particularly the depletion of NK cells, is a prominent feature of immunosuppression following severe tissue injury, heightening the susceptibility of severe trauma patients to life-threatening infections. Previous research indicates that the reduction in the number of NK cells is closely associated with the process of cell death. Nonetheless, the precise mechanism of NK cell death remains unknown. Here, we discovered that following severe traumatic injury, NK cells undergo several cell death pathways, dominated by apoptosis and pyroptosis with coexistence of necrotic cell death, immunogenic cell death, ferroptosis, and autophagy. These NK cells with different paradigms of death have diverse cytokine expression profiles and diverse interactions with other immune cells. Further exploration revealed that hypoxia was strongly associated with this diverse paradigm of NK cell death. Detailed investigation of paradigms of cell death may help to enhance comprehension of lymphopenia post-severe trauma, to develop new strategy in preventing immunosuppression, and then to improve outcome for severe trauma population.


Sujet(s)
Cellules tueuses naturelles , Plaies et blessures , Cellules tueuses naturelles/immunologie , Cellules tueuses naturelles/métabolisme , Humains , Plaies et blessures/immunologie , Plaies et blessures/anatomopathologie , Mâle , Autophagie , Ferroptose , Pyroptose , Apoptose , Animaux , Mort cellulaire , Cytokines/métabolisme , Femelle , Nécrose , Adulte
7.
Hortic Res ; 11(7): uhae143, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38988618

RÉSUMÉ

Targeted regulation using transgrafting technology has become a trend. However, the mechanisms of transgene-derived signal communication between rootstocks and scions remain unclear in woody plants. Here, we grafted wild-type (WT) walnut (Juglans regia L.) on WT (WT/WT), JrGA20ox1 (encodes a gibberellin 20-oxidase)-overexpressing (WT/OE), and JrGA20ox1-RNAi transformation (WT/RNAi) walnut in vitro. We aimed to elucidate the mechanisms of JrGA20ox1-derived signal communication under PEG-simulated drought stress between rootstocks and scions in walnut. We demonstrated that JrGA20ox1-OE and JrGA20ox1-RNAi rootstocks could transport active gibberellins (GAs) and JrGA20ox1-RNAi vector-produced sRNAs to WT scions under PEG-simulated drought stress, respectively. The movement of sRNAs further led to a successive decline in JrGA20ox1 expression and active GA content. Meanwhile, unknown mobile signals may move between rootstocks and scions. These mobile signals reduced the expression of a series of GA-responsive and GA-non-responsive genes, and induced ROS production in guard cells and an increase in ABA content, which may contribute to the drought tolerance of WT/RNAi, while the opposite occurred in WT/OE. The findings suggest that JrGA20ox1-derived rootstock-to-scion movement of signals is involved in drought tolerance of scions. Our research will provide a feasible approach for studying signal communication in woody plants.

8.
Comput Biol Med ; 180: 108931, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-39079414

RÉSUMÉ

Skin cancer images have hair occlusion problems, which greatly affects the accuracy of diagnosis and classification. Current dermoscopic hair removal methods use segmentation networks to locate hairs, and then uses repair networks to perform image repair. However, it is difficult to segment hair and capture the overall structure between hairs because of the hair being thin, unclear, and similar in color to the entire image. When conducting image restoration tasks, the only available images are those obstructed by hair, and there is no corresponding ground truth (supervised data) of the same scene without hair obstruction. In addition, the texture information and structural information used in existing repair methods are often insufficient, which leads to poor results in skin cancer image repair. To address these challenges, we propose the intersection-union dual-stream cross-attention Lova-SwinUnet (IUDC-LS). Firstly, we propose the Lova-SwinUnet module, which embeds Lovasz loss function into Swin-Unet, enabling the network to better capture features of various scales, thus obtaining better hair mask segmentation results. Secondly, we design the intersection-union (IU) module, which takes the mask results obtained in the previous step for pairwise intersection or union, and then overlays the results on the skin cancer image without hair to generate the labeled training data. This turns the unsupervised image repair task into the supervised one. Finally, we propose the dual-stream cross-attention (DC) module, which makes texture information and structure information interact with each other, and then uses cross-attention to make the network pay attention to the more important texture information and structure information in the fusion process of texture information and structure information, so as to improve the effect of image repair. The experimental results show that the PSNR index and SSIM index of the proposed method are increased by 5.4875 and 0.0401 compared with the other common methods. Experimental results unequivocally demonstrate the effectiveness of our approach, which serves as a potent tool for skin cancer detection, significantly surpassing the performance of comparable methods.


Sujet(s)
Poils , Tumeurs cutanées , Humains , Tumeurs cutanées/imagerie diagnostique , Poils/imagerie diagnostique , Algorithmes , Interprétation d'images assistée par ordinateur/méthodes , Dermoscopie/méthodes , Traitement d'image par ordinateur/méthodes
9.
Alzheimers Dement ; 20(8): 5674-5683, 2024 08.
Article de Anglais | MEDLINE | ID: mdl-38946708

RÉSUMÉ

INTRODUCTION: The study aimed to investigate the associations of changes in social isolation, loneliness, or both, with cognitive function. METHODS: Data were from 7299 older adults in the Chinese Longitudinal Healthy Longevity Survey. We defined four change patterns (no, incident, transient, and persistent) for social isolation and loneliness, and created nine-category variable to represent the joint changes. Tobit regression models and Cox models were performed. RESULTS: Incident, transient, and persistent social isolation or loneliness may accelerate cognitive decline (p < 0.05). Incident, transient, and persistent social isolation were associated with higher cognitive impairment risk, while only persistent loneliness was associated with higher cognitive impairment risk (p < 0.001). Notably, short-term or persistent social isolation was associated with accelerated cognitive decline and incident cognitive impairment, regardless of different loneliness change status (p < 0.05). DISCUSSION: Short-term or persistent social isolation and persistent loneliness may be a salient risk factor for cognitive decline and cognitive impairment. HIGHLIGHTS: Incident, transient, and persistent social isolation were associated with accelerated cognitive decline and higher cognitive impairment risk. Persistent loneliness was associated with accelerated cognitive decline and higher cognitive impairment risk. Short-term or persistent social isolation with concurrent different loneliness change status accelerated cognitive decline and higher cognitive impairment risk.


Sujet(s)
Dysfonctionnement cognitif , Solitude , Isolement social , Humains , Solitude/psychologie , Isolement social/psychologie , Mâle , Femelle , Sujet âgé , Dysfonctionnement cognitif/épidémiologie , Études longitudinales , Facteurs de risque , Cognition/physiologie , Études de cohortes , Chine/épidémiologie , Sujet âgé de 80 ans ou plus
10.
J Chromatogr A ; 1730: 465098, 2024 Aug 16.
Article de Anglais | MEDLINE | ID: mdl-38901295

RÉSUMÉ

The epoxy propanol molecular cage bonded silica stationary phase, RCC3-GLD@silica, synthesized through the ring-opening reaction of secondary amine with epoxy propanol using RCC3-R as the scaffold unit, was successfully prepared as confirmed by infrared spectroscopy, thermogravimetric analysis, and nitrogen adsorption-desorption characterization. This stationary phase demonstrated excellent separation performance in both reversed-phase and hydrophilic chromatography modes, effectively separating a wide variety of compounds including alkylbenzenes, polycyclic aromatic hydrocarbons, phenols, anilines, sulfonamides, nucleosides, amino acids, sugars, and acids. The development of RCC3-GLD@silica benefits from the synergistic effects of its hydrophobic and hydrophilic actions, as evidenced by the U-shaped characteristic of the retention factor for nucleoside compounds with changes in the aqueous content of the mobile phase, further confirming the simultaneous presence of reversed-phase and hydrophilic chromatography mechanisms. Not only did this stationary phase successfully separate 33 compounds in reversed-phase chromatography mode, but it also separated 54 compounds in hydrophilic interaction chromatography mode, showcasing its broad separation capability from weakly polar to strongly polar compounds on a single chromatographic column. This indicates a wide application prospect in the field of chromatographic analysis.


Sujet(s)
Chromatographie en phase inverse , Interactions hydrophobes et hydrophiles , Nucléosides , Silice , Silice/composition chimique , Chromatographie en phase inverse/méthodes , Nucléosides/isolement et purification , Nucléosides/composition chimique , Composés époxy/composition chimique , Acides aminés/isolement et purification , Acides aminés/composition chimique , Hydrocarbures aromatiques polycycliques/isolement et purification , Hydrocarbures aromatiques polycycliques/composition chimique , Phénols/isolement et purification , Phénols/composition chimique , Chromatographie en phase liquide à haute performance/méthodes
11.
J Sep Sci ; 47(12): e2400190, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38894562

RÉSUMÉ

An efficient method for the continuous separation of Voriconazole enantiomers was developed using sulfobutyl ether-ß-cyclodextrin (SBE-ß-CD) as a chiral selector in high-speed countercurrent chromatography (HSCCC) with different types. The separation was performed using a two-phase solvent system consisting of n-hexane/ethyl acetate/100 mmol/L phosphate buffer solution (pH = 3.0, containing 50 mmol/L SBE-ß-CD) (1.5:0.5:2, v/v/v). A fast and predictable scale-up process was achieved using an analytical DE HSCCC instrument. The optimized parameters were subsequently applied to a preparative Tauto HSCCC instrument, resulting in consistent separation time and enantiomeric purity, with throughput boosted by a remarkable 11-fold. Preparative HSCCC successfully separated 506 mg of the racemate, delivering enantiomers exceeding 99% purity as confirmed by high-performance liquid chromatography analysis. This investigation presents an effective methodology for forecasting the HSCCC scale-up process and attaining continuous separation of chiral drugs.


Sujet(s)
Distribution à contre-courant , Voriconazole , Distribution à contre-courant/méthodes , Stéréoisomérie , Voriconazole/composition chimique , Voriconazole/isolement et purification , Chromatographie en phase liquide à haute performance , Cyclodextrines bêta/composition chimique
12.
Cell Death Dis ; 15(5): 346, 2024 May 20.
Article de Anglais | MEDLINE | ID: mdl-38769124

RÉSUMÉ

Exploring novel diagnostic and therapeutic biomarkers is extremely important for osteosarcoma. YME1 Like 1 ATPase (YME1L), locating in the mitochondrial inner membrane, is key in regulating mitochondrial plasticity and metabolic activity. Its expression and potential functions in osteosarcoma are studied in the present study. We show that YME1L mRNA and protein expression is significantly elevated in osteosarcoma tissues derived from different human patients. Moreover, its expression is upregulated in various primary and immortalized osteosarcoma cells. The Cancer Genome Atlas database results revealed that YME1L overexpression was correlated with poor overall survival and poor disease-specific survival in sarcoma patients. In primary and immortalized osteosarcoma cells, silencing of YME1L through lentiviral shRNA robustly inhibited cell viability, proliferation, and migration. Moreover, cell cycle arrest and apoptosis were detected in YME1L-silenced osteosarcoma cells. YME1L silencing impaired mitochondrial functions in osteosarcoma cells, causing mitochondrial depolarization, oxidative injury, lipid peroxidation and DNA damage as well as mitochondrial respiratory chain complex I activity inhibition and ATP depletion. Contrarily, forced YME1L overexpression exerted pro-cancerous activity and strengthened primary osteosarcoma cell proliferation and migration. YME1L is important for Akt-S6K activation in osteosarcoma cells. Phosphorylation of Akt and S6K was inhibited after YME1L silencing in primary osteosarcoma cells, but was strengthened with YME1L overexpression. Restoring Akt-mTOR activation by S473D constitutively active Akt1 mitigated YME1L shRNA-induced anti-osteosarcoma cell activity. Lastly, intratumoral injection of YME1L shRNA adeno-associated virus inhibited subcutaneous osteosarcoma xenograft growth in nude mice. YME1L depletion, mitochondrial dysfunction, oxidative injury, Akt-S6K inactivation, and apoptosis were detected in YME1L shRNA-treated osteosarcoma xenografts. Together, overexpressed YME1L promotes osteosarcoma cell growth, possibly by maintaining mitochondrial function and Akt-mTOR activation.


Sujet(s)
Tumeurs osseuses , Prolifération cellulaire , Souris nude , Ostéosarcome , Animaux , Femelle , Humains , Mâle , Souris , Apoptose/génétique , ATPases associated with diverse cellular activities/métabolisme , ATPases associated with diverse cellular activities/génétique , Tumeurs osseuses/métabolisme , Tumeurs osseuses/anatomopathologie , Tumeurs osseuses/génétique , Lignée cellulaire tumorale , Mouvement cellulaire/génétique , Régulation de l'expression des gènes tumoraux , Souris de lignée BALB C , Mitochondries/métabolisme , Protéines mitochondriales/métabolisme , Protéines mitochondriales/génétique , Ostéosarcome/anatomopathologie , Ostéosarcome/génétique , Ostéosarcome/métabolisme , Protéines proto-oncogènes c-akt/métabolisme , Transduction du signal , Sérine-thréonine kinases TOR/métabolisme
13.
Heliyon ; 10(10): e31022, 2024 May 30.
Article de Anglais | MEDLINE | ID: mdl-38803867

RÉSUMÉ

Objective: To compare the clinical efficacy of endoscopic retrograde cholangiopancreatography (ERCP) combined with laparoscopic cholecystectomy (LC) and laparoscopic common bile duct exploration and lithotomy (LCBDE) in the treatment of cholecystolithiasis combined with bile duct stones. Methods: From September 2018 to January 2022, 195 patients with cholecystolithiasis complicated with extrahepatic bile duct stones from Department of Department of General Surgery, Shanghai Jiading Central Hospital met the inclusion criteria, including 60 cases in the LC group and 86 cases in the LCBDE group. The general condition, operation success rate, complications and residual stone rate of the two groups were retrospectively analyzed. Results: In the simultaneous operation group, 58 patients successfully performed ERCP, and the indwelling rate of the abdominal drainage tube (41.7 % vs. 95.3 %) was significantly better than that in the LCBDE group. There was no significant difference in the conversion rate to open surgery, operation time, and intraoperative blood loss between the two groups. In the simultaneous surgery group, 4 patients (6.7 %) developed pancreatitis after ERCP, which was cured by conservative treatment. The pain score at 6 h after operation was significantly lower than that in the LCBDE group (3.9 ± 1.6 vs 6.5 ± 2.4). There were no significant differences in biliary leakage (1.7 % vs. 4.7 %), postoperative cholangitis (5.0 % vs. 5.8 %), incision infection (3.3 % vs. 3.5 %), and bile duct stone residue rate (5.0 % vs 3.5 %) between the two groups. There was no severe pancreatitis, second operation or death. The duration of hospital stay was shortened in the concurrent operation group (5.1 ± 2.3d vs 7.9 ± 3.7d), and the operation cost was significantly higher than that in the LCBDE group (48839.9 ± 8549.5 vs 34635.9 ± 5893.7 yuan). Conclusion: ERCP combined with LC and LCBDE are both safe and effective methods for the treatment of cholecystolithiasis combined with extrahepatic bile duct stones. The simultaneous operation group has certain advantages in patient comfort and rapid rehabilitation, which can be popularized in qualified units.

14.
J Antibiot (Tokyo) ; 77(9): 627-633, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-38816449

RÉSUMÉ

Glutarimide-containing polyketides usually exhibit anti-fungi activity, which was well exampled by cycloheximide. In our work, three new polyketide structures, 12-amidestreptimidone (1), 12-carboxylstreptimidone (2) and 3-(5S,8R)-(2-amino-2-oxoethyl-2'-methoxy-2'-oxoethyl)-8,10-dimethyl-7-oxododeca-5-hydroxy-9E,11-diolefin (3) were isolated from Streptomyces sp. JCM 4793. 3 without the glutarimide moiety is not active against fungi as expected, while 1 bearing the amide moiety is much more active than its carboxylic form 2. Here we report the isolation, structural elucidation, antifungal activity, and proposed biosynthesis pathway of 1-3.


Sujet(s)
Antifongiques , Polycétides , Streptomyces , Streptomyces/métabolisme , Streptomyces/composition chimique , Polycétides/pharmacologie , Polycétides/composition chimique , Polycétides/isolement et purification , Antifongiques/pharmacologie , Antifongiques/composition chimique , Antifongiques/isolement et purification , Humains , Tests de sensibilité microbienne , Pipéridones/pharmacologie , Pipéridones/composition chimique , Pipéridones/isolement et purification , Structure moléculaire
15.
Sci China Life Sci ; 67(8): 1579-1590, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38676814

RÉSUMÉ

Plant genomics and crop breeding are at the intersection of biotechnology and information technology. Driven by a combination of high-throughput sequencing, molecular biology and data science, great advances have been made in omics technologies at every step along the central dogma, especially in genome assembling, genome annotation, epigenomic profiling, and transcriptome profiling. These advances further revolutionized three directions of development. One is genetic dissection of complex traits in crops, along with genomic prediction and selection. The second is comparative genomics and evolution, which open up new opportunities to depict the evolutionary constraints of biological sequences for deleterious variant discovery. The third direction is the development of deep learning approaches for the rational design of biological sequences, especially proteins, for synthetic biology. All three directions of development serve as the foundation for a new era of crop breeding where agronomic traits are enhanced by genome design.


Sujet(s)
Génomique , Plantes , Logiciel , Plantes/génétique , Sélection , Génome végétal , Cartographie chromosomique , Protéines végétales/composition chimique , Protéines végétales/génétique , Science des données
16.
Neurobiol Pain ; 15: 100156, 2024.
Article de Anglais | MEDLINE | ID: mdl-38601267

RÉSUMÉ

Background and aims: Spinal cord injury (SCI) affects roughly 300,000 Americans with 17,000 new cases added annually. In addition to paralysis, 60% of people with SCI develop neurogenic bowel (NB), a syndrome characterized by slow colonic transit, constipation, and chronic abdominal pain. The knowledge gap surrounding NB mechanisms after SCI means that interventions are primarily symptom-focused and largely ineffective. The goal of the present studies was to identify mechanism(s) that initiate and maintain NB after SCI as a critical first step in the development of evidence-based, novel therapeutic treatment options. Methods: Following spinal contusion injury at T9, we observed alterations in bowel structure and function reflecting key clinical features of NB. We then leveraged tissue-specific whole transcriptome analyses (RNAseq) and fecal 16S rRNA amplicon sequencing in combination with histological, molecular, and functional (Ca2+ imaging) approaches to identify potential mechanism(s) underlying the generation of the NB phenotype. Results: In agreement with prior reports focused on SCI-induced changes in the skin, we observed a rapid and persistent increase in expression of calcitonin gene-related peptide (CGRP) expression in the colon. This is suggestive of a neurogenic inflammation-like process engaged by antidromic activity of below-level primary afferents following SCI. CGRP has been shown to disrupt colon homeostasis and negatively affect peristalsis and colon function. As predicted, contusion SCI resulted in increased colonic transit time, expansion of lymphatic nodules, colonic structural and genomic damage, and disruption of the inner, sterile intestinal mucus layer corresponding to increased CGRP expression in the colon. Gut microbiome colonization significantly shifted over 28 days leading to the increase in Anaeroplasma, a pathogenic, gram-negative microbe. Moreover, colon specific vagal afferents and enteric neurons were hyperresponsive after SCI to different agonists including fecal supernatants. Conclusions: Our data suggest that SCI results in overexpression of colonic CGRP which could alter colon structure and function. Neurogenic inflammatory-like processes and gut microbiome dysbiosis can also sensitize vagal afferents, providing a mechanism for visceral pain despite the loss of normal sensation post-SCI. These data may shed light on novel therapeutic interventions targeting this process to prevent NB development in patients.

17.
Ecotoxicol Environ Saf ; 274: 116176, 2024 Apr 01.
Article de Anglais | MEDLINE | ID: mdl-38479309

RÉSUMÉ

Ambient air pollution is a major global health concern. Yet, no study has thoroughly assessed its link to respiratory mortality. Our research evaluated the combined and individual effects of air pollutants on respiratory mortality risks based on the UK Biobank. A total of 366,478 participants were studied. A Cox proportional hazards model was used to estimate the respiratory mortality risk from combined long-term exposure to five pollutants, summarized as a weighted air pollution score. During a median of 13.6 years of follow-up, 6113 deaths due to respiratory diseases were recorded. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) of respiratory diseases were 2.64 (2.05-3.39), 1.62 (1.23-2.12), 2.06 (1.73-2.45), 1.20 (1.16-1.25), and 1.07 (1.05-1.08) per 10 µg/m3 increase in PM2.5, PM2.5-10, PM10, NO2, and NOx, respectively. The air pollution score showed a dose-response association with an elevated respiratory mortality risk. The highest versus lowest quartile air pollution score was linked to a 44% increase in respiratory mortality risk (HR 1.44, 95% CI: 1.33-1.57), with consistent findings in subgroup and sensitivity analyses. Long-term individual and joint air-pollutant exposure showed a dose-response association with an increased respiratory mortality risk, highlighting the importance of a comprehensive air-pollutant assessment to protect public health.


Sujet(s)
Polluants atmosphériques , Pollution de l'air , Maladies de l'appareil respiratoire , Humains , Polluants atmosphériques/effets indésirables , Polluants atmosphériques/analyse , Matière particulaire/toxicité , Matière particulaire/analyse , Études prospectives , Exposition environnementale/effets indésirables , Exposition environnementale/analyse , Pollution de l'air/effets indésirables , Pollution de l'air/analyse , Maladies de l'appareil respiratoire/épidémiologie , Dioxyde d'azote
18.
Article de Anglais | MEDLINE | ID: mdl-38442634

RÉSUMÉ

In this work, a high-speed shear extraction off-line coupling high-speed countercurrent chromatography method was developed to separate maslinic acid and oleanolic acid from olive pomace. To improve extraction efficiency, the polar disparity between maslinic acid and oleanolic acid necessitated the concurrent utilization of both polar and non-polar solvents during high-speed shear extraction. Then, the high-speed shear extraction was directly feed to high-speed countercurrent chromatography for subsequently separation. A total of 250 min were needed to complete the extraction and separation process. This yielded two molecules from 3.3 g of defatted olive pomace: 7.2 mg of 93.8 % pure maslinic acid and 2.3 mg of 90.1 % pure oleanolic acid, both determined by HPLC at 210 nm. Furthermore, the compounds exhibited inhibitory activity against Escherichia coli and Staphylococcus aureus. At a concentration of 100 µg/mL, its efficacy in inhibiting hyaluronidase was comparable to that of the standard drug indomethacin. Compared with the conventional separation method, this coupled technique reduced the whole time due to the direct injection of sample extraction solution. This technique provides a useful approach for the separation of natural products with significant polarity differences.


Sujet(s)
Olea , Acide oléanolique , Acide oléanolique/analogues et dérivés , Triterpènes , Acide oléanolique/analyse , Olea/composition chimique , Distribution à contre-courant , Antibactériens/pharmacologie , Triterpènes/composition chimique , Chromatographie en phase liquide à haute performance , Extraits de plantes/pharmacologie , Extraits de plantes/analyse
19.
Clin Transl Gastroenterol ; 15(4): e00690, 2024 Apr 01.
Article de Anglais | MEDLINE | ID: mdl-38334941

RÉSUMÉ

ABSTRACT: Hepatocellular carcinoma (HCC) remains a formidable oncological challenge, calling for innovative therapeutic strategies to improve patient outcomes. MicroRNAs have emerged as key regulators in cancer, and miR-3682-3p shows potential as a diagnostic and prognostic biomarker in HCC. We conducted a comprehensive study to uncover its role in HCC biology, revealing dysregulation and clinical associations. Target gene analysis provided insights into potential molecular mechanisms. Moreover, we explored its impact on the tumor microenvironment, immune cell infiltration, and therapy responses. Our findings highlight miR-3682-3p as a promising candidate for further investigations and potential therapeutic strategies in HCC management.


Sujet(s)
Carcinome hépatocellulaire , Tumeurs du foie , microARN , Microenvironnement tumoral , Femelle , Humains , Mâle , Marqueurs biologiques tumoraux/génétique , Marqueurs biologiques tumoraux/métabolisme , Carcinome hépatocellulaire/génétique , Carcinome hépatocellulaire/anatomopathologie , Lignée cellulaire tumorale , Analyse de profil d'expression de gènes , Régulation de l'expression des gènes tumoraux , Tumeurs du foie/génétique , Tumeurs du foie/anatomopathologie , microARN/génétique , microARN/métabolisme , Pronostic , Microenvironnement tumoral/immunologie , Microenvironnement tumoral/génétique
20.
J Chromatogr A ; 1718: 464724, 2024 Mar 15.
Article de Anglais | MEDLINE | ID: mdl-38350351

RÉSUMÉ

In this work, two different multiple dual-mode (MDM) counter-current chromatography methods, conventional MDM and modified MDM elution modes, were compared for the chiral separation of the ketoconazole enantiomers. The biphasic solvent system which consisted of n-hexane: isobutyl acetate: 0.1 mol/L phosphate buffer (2:4:6, v/v) (pH = 8.5) was employed as stationary phase and mobile phase. And the hydroxypropyl-ß-cyclodextrin (HP-ß-CD) with a concentration of 100 mmol/L was dissolved in the phosphate buffer, as the chiral selector. Under two different methods, dual-mode (DM) elution was performed to determine the time of the transformed phase roles and multiple cycles were performed to isolate ketoconazole, respectively. The result indicated that the modified MDM elution had a significant improvement on the separation, increasing the resolution from 0.51 to 1.19, while the resolution was increased from 0.40 to 0.79 by the conventional MDM elution. Ultimately, baseline separation of ketoconazole enantiomers was essentially achieved by high-speed counter-current chromatography under optimized modified MDM separation conditions. The final recoveries of the two enantiomers, R-(K) and S-(K), were 92.5 % and 83.3 %, respectively, corresponding to enantiomeric excess values of 99.0 % and 97.0 %, as determined by HPLC.


Sujet(s)
Cyclodextrines bêta , Cyclodextrines bêta/composition chimique , Distribution à contre-courant/méthodes , Kétoconazole , 2-Hydroxypropyl-beta-cyclodextrin , Stéréoisomérie , Phosphates
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