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1.
J Neurol ; 2024 Jul 02.
Article de Anglais | MEDLINE | ID: mdl-38954034

RÉSUMÉ

OBJECTIVE: To evaluate the effectiveness and safety of nusinersen for the treatment of 5q-spinal muscular atrophy (SMA) among Chinese pediatric patients. METHODS: Using a longitudinal, multi-center registry, both prospective and retrospective data were collected from pediatric patients with 5q-SMA receiving nusinersen treatment across 18 centers in China. All patients fulfilling the eligibility criteria were included consecutively. Motor function outcomes were assessed post-treatment by SMA type. Safety profile was evaluated among patients starting nusinersen treatment post-enrollment. Descriptive analyses were used to report baseline characteristics, effectiveness, and safety results. RESULTS: As of March 2nd, 2023, 385 patients were included. Most patients demonstrated improvements or stability in motor function across all SMA types. Type II patients demonstrated mean changes [95% confidence interval (CI)] of 4.4 (3.4-5.4) and 4.1 (2.8-5.4) in Hammersmith Functional Motor Scale-Expanded (HFMSE), and 2.4 (1.7-3.1) and 2.3 (1.2-3.4) in Revised Upper Limb Module (RULM) scores at months 6 and 10. Type III patients exhibited mean changes (95% CI) of 3.9 (2.5-5.3) and 4.3 (2.6-6.0) in HFMSE, and 2.1 (1.2-3.0) and 1.5 (0.0-3.0) in RULM scores at months 6 and 10. Of the 132 patients, 62.9% experienced adverse events (AEs). Two patients experienced mild AEs (aseptic meningitis and myalgia) considered to be related to nusinersen by the investigator, with no sequelae. CONCLUSIONS: These data underscore the significance of nusinersen in Chinese pediatric patients with SMA regarding motor function improvement or stability, and support recommendations on nusinersen treatment by Chinese SMA guidelines and continuous coverage of nusinersen by basic medical insurance.

2.
Arch Toxicol ; 2024 Jul 02.
Article de Anglais | MEDLINE | ID: mdl-38955863

RÉSUMÉ

5F-EDMB-PICA is a newly emerged synthetic cannabinoid which has been characterized in relevant literature in recent years. Although phase-I metabolites of 5F-EDMB-PICA have been partly reported, the phase-II metabolism of this synthetic cannabinoid has not been studied yet. In this study, we established a phase-I and phase-II metabolism model in vitro by using pooled human liver microsomes, NADPH regeneration system, and UGT incubation system, with 1 mg/ml 5F-EDMB-PICA added and incubated at 37 °C for 60 min. The metabolites were analyzed by Q Exactive™ Hybrid Quadrupole-Orbitrap™ Mass Spectrometer, via which we discovered and identified 14 phase-I metabolites and 4 phase-II metabolites of 5F-EDMB-PICA, involving pathways such as ester hydrolysis, dehydrogenation, hydrolytic defluorination, hydroxylation, dihydroxylation, glucuronidation, and combinations of the pathways mentioned above. We recommend considering the monohydroxylation metabolites (M9, M10) with higher content and intact ester and 5-fluoropentyl structures as potential biomarkers of 5F-EDMB-PICA.

3.
J Agric Food Chem ; 2024 Jul 03.
Article de Anglais | MEDLINE | ID: mdl-38959381

RÉSUMÉ

Benzimidazoles, the representative pharmacophore of fungicides, have excellent antifungal potency, but their simple structure and single site of action have hindered their wider application in agriculture. In order to extend the structural diversity of tubulin-targeted benzimidazoles, novel benzimidazole derivatives were prepared by introducing the attractive pyrimidine pharmacophore. 2-((6-(4-(trifluoromethyl)phenoxy)pyrimidin-4-yl)thio)-1H-benzo[d]imidazole (A25) exhibited optimal antifungal activity against Sclerotinia sclerotiorum (S. s.), affording an excellent half-maximal effective concentration (EC50) of 0.158 µg/mL, which was higher than that of the reference agent carbendazim (EC50 = 0.594 µg/mL). Pot experiments revealed that compound A25 (200 µg/mL) had acceptable protective activity (84.7%) and curative activity (78.1%), which were comparable with that of carbendazim (protective activity: 90.8%; curative activity: 69.9%). Molecular docking displayed that multiple hydrogen bonds and π-π interactions could be formed between A25 and ß-tubulin, resulting in a stronger bonding effect than carbendazim. Fluorescence imaging revealed that the structure of intracellular microtubules can be changed significantly after A25 treatment. Overall, these remarkable antifungal profiles of constructed novel benzimidazole derivatives could facilitate the application of novel microtubule-targeting agents.

4.
J Biomed Opt ; 29(7): 076002, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38966847

RÉSUMÉ

Significance: Optical coherence tomography has great utility for capturing dynamic processes, but such applications are particularly data-intensive. Samples such as biological tissues exhibit temporal features at varying time scales, which makes data reduction challenging. Aim: We propose a method for capturing short- and long-term correlations of a sample in a compressed way using non-uniform temporal sampling to reduce scan time and memory overhead. Approach: The proposed method separates the relative contributions of white noise, fluctuating features, and stationary features. The method is demonstrated on mammary epithelial cell spheroids in three-dimensional culture for capturing intracellular motility without loss of signal integrity. Results: Results show that the spatial patterns of motility are preserved and that hypothesis tests of spheroids treated with blebbistatin, a motor protein inhibitor, are unchanged with up to eightfold compression. Conclusions: The ability to measure short- and long-term correlations compressively will enable new applications in (3+1)D imaging and high-throughput screening.


Sujet(s)
Tomographie par cohérence optique , Tomographie par cohérence optique/méthodes , Humains , Sphéroïdes de cellules/effets des médicaments et des substances chimiques , Mouvement cellulaire/physiologie , Mouvement cellulaire/effets des médicaments et des substances chimiques , Traitement d'image par ordinateur/méthodes , Cellules épithéliales/effets des médicaments et des substances chimiques , Algorithmes , Composés hétérocycliques avec 4 noyaux ou plus
5.
BMC Public Health ; 24(1): 1767, 2024 Jul 02.
Article de Anglais | MEDLINE | ID: mdl-38956480

RÉSUMÉ

BACKGROUND: Women at middle age are puzzled by a series of menopausal disturbances, can be distressing and considerably affect the personal, social and work lives. We aim to estimate the global prevalence of nineteen menopausal symptoms among middle-aged women by performing a systematic review and meta-analysis. METHODS: Comprehensive search was performed in multiple databases from January, 2000 to March, 2023 for relevant studies. Random-effect model with double-arcsine transformation was used for data analysis. RESULTS: A total of 321 studies comprised of 482,067 middle-aged women were included for further analysis. We found varied prevalence of menopausal symptoms, with the highest prevalence of joint and muscular discomfort (65.43%, 95% CI 62.51-68.29) and lowest of formication (20.5%, 95% CI 13.44-28.60). Notably, South America shared dramatically high prevalence in a sort of menopausal symptoms including depression and urogenital symptoms. Besides, countries with high incomes (49.72%) had a significantly lower prevalence of hot flashes than those with low (65.93%), lower-middle (54.17%), and upper-middle (54.72%, p < 0.01), while personal factors, such as menopausal stage, had an influence on most menopausal symptoms, particularly in vaginal dryness. Prevalence of vagina dryness in postmenopausal women (44.81%) was 2-fold higher than in premenopausal women (21.16%, p < 0.01). Furthermore, a remarkable distinction was observed between body mass index (BMI) and prevalence of sleep problems, depression, anxiety and urinary problems. CONCLUSION: The prevalence of menopausal symptoms affected by both social and personal factors which calls for attention from general public.


Sujet(s)
Bouffées de chaleur , Ménopause , Humains , Femelle , Ménopause/physiologie , Prévalence , Adulte d'âge moyen , Bouffées de chaleur/épidémiologie , Santé mondiale/statistiques et données numériques
6.
ACS Sens ; 2024 Jul 05.
Article de Anglais | MEDLINE | ID: mdl-38967239

RÉSUMÉ

Limited by insufficient active sites and restricted mechanical strength, designing reliable and wearable gas sensors with high activity and ductility remains a challenge for detecting hazardous gases. In this work, a thermally induced and solvent-assisted oxyanion etching strategy was implemented for selective pore opening in a rigid microporous Cu-based metal-organic framework (referred to as CuM). A conductive CuM/MXene aerogel was then self-assembled through cooperative hydrogen bonding interactions between the carbonyl oxygen atom in PVP grafted on the surface of defect-rich Cu-BTC and the surface functional hydroxyl group on MXene. A flexible NO2 sensing performance using the CuM/MXene aerogel hybridized sodium alginate hydrogel is finally achieved, demonstrating extraordinary sensitivity (S = 52.47 toward 50 ppm of NO2), good selectivity, and rapid response/recovery time (0.9/4.5 s) at room temperature. Compared with commercial sensors, the relative error is less than 7.7%, thereby exhibiting significant potential for application in monitoring toxic and harmful gases. This work not only provides insights for guiding rational synthesis of ideal structure models from MOF composites but also inspires the development of high-performance flexible gas sensors for potential multiscenario applications.

7.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 40(6): 481-487, 2024 Jun.
Article de Chinois | MEDLINE | ID: mdl-38952086

RÉSUMÉ

Objective To elucidate the role of chaperone-mediated autophagy (CMA) in alleviating emotional dysfunction in mice with sepsis-associated encephalopathy (SAE). Methods The SAE mouse model was established by cecal ligation and perforation (CLP). The severity of sepsis was assessed using the sepsis severity score (MSS). Emotional function in SAE mice was assessed by the open-field test and elevated plus-maze. The expression levels of cognitive heat shock cognate protein 70 (HSC70), lysosomal-associated membrane protein 2A (LAMP2A) and high mobility group box 1 protein B1 (HMGB1) were detected using Western blotting. Co-localization of LAMP2A in the hippocampal neurons was observed by immunofluorescence. The release of inflammatory factors interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) was measured using ELISA. Following 12 hours post-CLP, mice were orally administered resveratrol at a dose of 30 mg/kg once daily until day 14. Results The mortality rate of CLP mice was 45.83% 24 days post CLP, and all surviving mice exhibited emotional disturbances. 24 hours after CLP, a significant decrease in HSC70 and LAMP2A expression in hippocampal neurons was observed, indicating impaired CMA activity. Meanwhile, HMGB1 and inflammatory cytokines (IL-6 and TNF-α) levels increased. After resveratrol treatment, an increase of HSC70 and LAMP2A expression, and a decrease of HMGB1 expression and inflammatory cytokine release were observed, suggesting enhanced CMA activity and reduced neuroinflammation. Behavioral tests showed that emotional dysfunction was improved in SAE mice after resveratrol treatment. Conclusion CMA activity of hippocampal neurons in SAE mice is significantly reduced, leading to emotional dysfunction. Resveratrol can alleviate neuroinflammation and emotional dysfunction in SAE mice by promoting CMA and inhibiting the expression of HMGB1 and the release of inflammatory factors.


Sujet(s)
Autophagie médiée par les chaperonnes , Protéine HMGB1 , Resvératrol , Encéphalopathie associée au sepsis , Animaux , Souris , Encéphalopathie associée au sepsis/traitement médicamenteux , Encéphalopathie associée au sepsis/physiopathologie , Encéphalopathie associée au sepsis/métabolisme , Mâle , Resvératrol/pharmacologie , Protéine HMGB1/métabolisme , Autophagie médiée par les chaperonnes/effets des médicaments et des substances chimiques , Facteur de nécrose tumorale alpha/métabolisme , Protéine de membrane-2 associée au lysosome/métabolisme , Protéine de membrane-2 associée au lysosome/génétique , Maladies neuro-inflammatoires/traitement médicamenteux , Maladies neuro-inflammatoires/étiologie , Maladies neuro-inflammatoires/métabolisme , Hippocampe/métabolisme , Hippocampe/effets des médicaments et des substances chimiques , Interleukine-6/métabolisme , Stilbènes/pharmacologie , Protéines du choc thermique HSC70/métabolisme , Sepsie/complications , Sepsie/traitement médicamenteux , Sepsie/métabolisme , Sepsie/physiopathologie , Souris de lignée C57BL , Modèles animaux de maladie humaine
8.
J Multidiscip Healthc ; 17: 3029-3039, 2024.
Article de Anglais | MEDLINE | ID: mdl-38948396

RÉSUMÉ

Background: Maternity health management has always been the area of concern and considering, and considering its complexity and multidisciplinary, it is necessary to provide effective training for healthcare workers. Purpose: To evaluate the impact of a multidisciplinary experiential training model on the knowledge, attitude, and practice of healthcare workers in maternity health management. Patients and Methods: We conducted a novel educational model, Multidisciplinary Maternity Health Experiential Training based on Knowledge, Attitude and Practice (MMHET), which combined theoretical knowledge, practical skills, and human-centred humanistic care, offering a comprehensive offline education program supported by online teaching materials structured around knowledge graphs. Pre- and post-test surveys were used to assess the changes in participants' knowledge, attitudes, and practices. Results: From May to July 2023, a total of 322 participants attended the course, and only a small percentage had participated in experiential training. For all topics, the vast majority of participants endorsed the course, and the attitude content had the highest percentage of participants who said they agreed. Among the groups with different years of working life, the highest percentage of participants in the >20 years group strongly endorsed the course. Conclusion: The preliminary findings indicate that the MMHET model is well-received and feasible, demonstrating its potential to enhance maternity health management education.

9.
Front Pharmacol ; 15: 1371890, 2024.
Article de Anglais | MEDLINE | ID: mdl-38948467

RÉSUMÉ

Introduction: Rhubarb is a frequently used and beneficial traditional Chinese medicine. Wild resources of these plants are constantly being depleted, meaning that rhubarb products have been subjected to an unparalleled level of adulteration. Consequentially, reliable technology is urgently required to verify the authenticity of rhubarb raw materials and commercial botanical drugs. Methods: In this study, the barcode-DNA high-resolution melting (Bar-HRM) method was applied to characterize 63 rhubarb samples (five Polygonaceae species: Rheum tanguticum, Rh. palmatum, Rh. officinale, Rumex japonicus and Ru. sp.) and distinguish the rhubarb contents of 24 traditional Chinese patent medicine (TCPM) samples. Three markers, namely ITS2, rbcL and psbA-trnH, were tested to assess the candidate DNA barcodes for their effectiveness in distinguishing rhubarb from its adulterants. A segment from ITS2 was selected as the most suitable mini-barcode to identify the botanical drug rhubarb in TCPMs. Then, rhubarbs and TCPM samples were subjected to HRM analysis based on the ITS2 barcode. Results: Among the tested barcoding loci, ITS2 displayed abundant sites of variation and was effective in identifying Polygonaceae species and their botanical origins. HRM analysis based on the ITS2 mini-barcode region successfully distinguished the authenticity of five Polygonaceae species and eight batches of TCPMs. Of the 18 TCPM samples, 66.7 % (12 samples) were identified as containing Rh. tanguticum or Rh. officinale. However, 33.3 % were shown to consist of adulterants. Conclusions: These results demonstrated that DNA barcoding combined with HRM is a specific, suitable and powerful approach for identifying rhubarb species and TCPMs, which is crucial to guaranteeing the security of medicinal plants being traded internationally.

10.
Poult Sci ; 103(9): 103929, 2024 Jun 01.
Article de Anglais | MEDLINE | ID: mdl-38943802

RÉSUMÉ

This study aimed to investigate the developmental change of body growth and gene expression related to fatty acid uptake and oxidation in the yolk sac membrane (YSM) and jejunum during embryogenesis in Muscovy ducks. The weights of embryos and yolk sac (YS) (5 embryos per replicate, n = 6) were recorded on embryonic days (E)16, E19, E22, E25, E28, E31, and the day of hatch (DOH). The fat and fatty acid contents in YSM, jejunal histology, and gene expression related to fatty acid metabolism in YSM and jejunum were determined in each sampling time. Among the nonlinear models, the maximum growth is estimated at 2.83 (E22.5), 2.67 (E22.1), and 2.60 (E21.3) g/d using logistic, Gompertz, and Von Bertalanffy models, respectively. The weight of YS, and ether extract-free YS as well as the amounts of fat and fatty acids in YS decreased (P < 0.05) linearly, whereas the villus height, crypt depth, villus height/crypt depth, and musculature thickness in jejunum increased (P < 0.05) linearly during embryogenesis. The mRNA expression of CD36, SLC27A4, and FABP1 related to fatty acid uptake as well as the mRNA and protein expressions of PPARα and CPT1 related to fatty acid oxidation increased in a quadratic manner (P < 0.05) in both YS and jejunum, and the maximum values were achieved during E25 to E28. In conclusion, the maximum growth rate of Muscovy duck embryos was estimated at 2.60 to 2.83 g/d on E21.3 to E23.5, while the accumulations of lipid and fatty acid in YS were decreased in association with the increased absorptive area of morphological structures in jejunum. The gene and protein expression involved in fatty acid metabolism displayed a similar enhancement pattern between YSM and jejunum during E25 to E28, suggesting that fatty acid utilization could be strengthened to meet the energy demand for embryonic development.

11.
Int J Biol Macromol ; 274(Pt 1): 133298, 2024 Jun 24.
Article de Anglais | MEDLINE | ID: mdl-38917918

RÉSUMÉ

BACKGROUND: Placental exosomes are a kind of intercellular communication media secreted by placental cells during pregnancy, exosomogenesis and release are regulated by many secretory glycoproteins. CREG1 is a kind of secreted glycoprotein widely expressed in various organs and tissues of the body, which inhibits cell proliferation and enhances cell differentiation. The aim of this study was to explore the role of CREG1 in regulating exosomogenesis during the proliferation and differentiation of placental trophoblast cells in early pregnant dairy cows by targeting IGF2R and participating in regulating organoid differentiation via exosomes transport. METHODS: Molecular biological methods were firstly used to investigate the expression patterns of CREG1, IGF2R and exosomal marker proteins in early placental development of pregnant dairy cows. Subsequently, the effects of CREG1 on the formation and release of bovine placental trophoblast (BTCs) derived exosomes by targeting IGF2R were investigated. Further, the effects of CREG1 on the change of gene expression patterns along with the transport of exosomes to recipient cells and participate in regulating the differentiation of organoids were explored. RESULTS: The expression of CREG1, IGF2R and exosomal marker proteins increased with the increase of pregnancy months during the early evolution of placental trophoblast cells in dairy cows. Overexpression of Creg1 enhanced the genesis and release of exosomes derived from BTCs, while knocking down the expression of Igf2r gene not only inhibited the genesis of exosomes, but also inhibited the genesis and release of exosomes induced by overexpression of CREG1 protein. Interestingly, IGF2R can regulate the expression of CREG1 through reverse secretion. What's more, the occurrence and release of trophoblast-derived exosomes are regulated by CREG1 binding to IGF2R, which subsequently binds to Rab11. CREG1 can not only promote the formation and release of exosomes in donor cells, but also regulate the change of gene expression patterns along with the transport of exosomes to recipient cells and participate in regulating the early development of placenta. CONCLUSIONS: Our study confirmed that CREG1 is involved in the exosomogenesis and release of exosomes during the proliferation and differentiation of placental trophoblast cells in early pregnant dairy cows by targeting IGF2R, and is involved in the regulation of organoid differentiation through exosome transport.

12.
Biodes Res ; 6: 0038, 2024.
Article de Anglais | MEDLINE | ID: mdl-38919710

RÉSUMÉ

Recently, there has been increasing interest in the use of bacteria for cancer therapy due to their ability to selectively target tumor sites and inhibit tumor growth. However, the complexity of the interaction between bacteria and tumor cells evokes unpredictable therapeutic risk, which induces inflammation, stimulates the up-regulation of cyclooxygenase II (COX-2) protein, and stimulates downstream antiapoptotic gene expression in the tumor microenvironment to reduce the antitumor efficacy of chemotherapy and immunotherapy. In this study, we encapsulated celecoxib (CXB), a specific COX-2 inhibitor, in liposomes anchored to the surface of Escherichia coli Nissle 1917 (ECN) through electrostatic absorption (C@ECN) to suppress ECN-induced COX-2 up-regulation and enhance the synergistic antitumor effect of doxorubicin (DOX). C@ECN improved the antitumor effect of DOX by restraining COX-2 expression. In addition, local T lymphocyte infiltration was induced by the ECN to enhance immunotherapy efficacy in the tumor microenvironment. Considering the biosafety of C@ECN, a hypoxia-induced lysis circuit, pGEX-Pvhb-Lysis, was introduced into the ECN to limit the number of ECNs in vivo. Our results indicate that this system has the potential to enhance the synergistic effect of ECN with chemical drugs to inhibit tumor progression in medical oncology.

13.
Proc Natl Acad Sci U S A ; 121(25): e2321614121, 2024 Jun 18.
Article de Anglais | MEDLINE | ID: mdl-38857401

RÉSUMÉ

The medial prefrontal cortex (mPFC) is a key brain structure for higher cognitive functions such as decision-making and goal-directed behavior, many of which require awareness of spatial variables including one's current position within the surrounding environment. Although previous studies have reported spatially tuned activities in mPFC during memory-related trajectory, the spatial tuning of mPFC network during freely foraging behavior remains elusive. Here, we reveal geometric border or border-proximal representations from the neural activity of mPFC ensembles during naturally exploring behavior, with both allocentric and egocentric boundary responses. Unlike most of classical border cells in the medial entorhinal cortex (MEC) discharging along a single wall, a large majority of border cells in mPFC fire particularly along four walls. mPFC border cells generate new firing fields to external insert, and remain stable under darkness, across distinct shapes, and in novel environments. In contrast to hippocampal theta entrainment during spatial working memory tasks, mPFC border cells rarely exhibited theta rhythmicity during spontaneous locomotion behavior. These findings reveal spatially modulated activity in mPFC, supporting local computation for cognitive functions involving spatial context and contributing to a broad spatial tuning property of cortical circuits.


Sujet(s)
Cortex préfrontal , Rythme thêta , Cortex préfrontal/physiologie , Cortex préfrontal/cytologie , Animaux , Rythme thêta/physiologie , Mâle , Souris , Cortex entorhinal/physiologie , Neurones/physiologie , Hippocampe/physiologie , Mémoire spatiale/physiologie , Souris de lignée C57BL , Mémoire à court terme/physiologie
14.
J Robot Surg ; 18(1): 238, 2024 Jun 04.
Article de Anglais | MEDLINE | ID: mdl-38833096

RÉSUMÉ

The objective of this meta-analysis was to assess the comparative efficacy of robot-assisted and laparoscopic surgery in treating gastric cancer among patients characterized by a high visceral fat area (VFA). In April 2024, we conducted a comprehensive literature review using major international databases, such as PubMed, Embase, and Google Scholar. We restricted our selection to articles written in English, excluding reviews, protocols without published data, conference abstracts, and irrelevant content. Our analysis focused on continuous data using 95% confidence intervals (CIs) and standard mean differences (SMDs), while dichotomous data were assessed with odds ratios (ORs) and 95% CIs. We set the threshold for statistical significance at P < 0.05. Data extraction included baseline characteristics, primary outcomes (such as operative time, major complications, lymph node yield, and anastomotic leakage), and secondary outcomes. The meta-analysis included three cohort studies totaling 970 patients. The robotic-assisted group demonstrated a significantly longer operative time compared to the laparoscopic group, with a weighted mean difference (WMD) of - 55.76 min (95% CI - 74.03 to - 37.50; P < 0.00001). This group also showed a reduction in major complications, with an odds ratio (OR) of 2.48 (95% CI 1.09-5.66; P = 0.03) and fewer occurrences of abdominal infections (OR 3.17, 95% CI 1.41-7.14; P = 0.005), abdominal abscesses (OR 3.83, 95% CI 1.53-9.57; P = 0.004), anastomotic leaks (OR 4.09, 95% CI 1.73-9.65; P = 0.001), and pancreatic leaks (OR 8.93, 95% CI 2.33-34.13; P = 0.001). However, no significant differences were observed between the groups regarding length of hospital stay, overall complications, estimated blood loss, or lymph node yield. Based on our findings, robot-assisted gastric cancer surgery in obese patients with visceral fat appears to be correlated with fewer major complications compared to laparoscopic surgery, while maintaining similar outcomes in other surgical aspects. However, it is important to note that robot-assisted procedures do tend to have longer operative times.


Sujet(s)
Laparoscopie , Obésité abdominale , Durée opératoire , Interventions chirurgicales robotisées , Tumeurs de l'estomac , Humains , Laparoscopie/méthodes , Interventions chirurgicales robotisées/méthodes , Interventions chirurgicales robotisées/effets indésirables , Tumeurs de l'estomac/chirurgie , Résultat thérapeutique , Obésité abdominale/complications , Complications postopératoires/étiologie , Complications postopératoires/épidémiologie , Gastrectomie/méthodes , Désunion anastomotique/étiologie , Désunion anastomotique/épidémiologie
16.
Cell Mol Biol Lett ; 29(1): 90, 2024 Jun 14.
Article de Anglais | MEDLINE | ID: mdl-38877403

RÉSUMÉ

The membrane-delimited receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), angiotensin-converting enzyme 2 (ACE2), which is expressed in the intestine, collaborates with broad neutral amino acid transporter 1 (B0AT1). Tryptophan (Trp) is transported into intestinal epithelial cells by ACE2 and B0AT1. However, whether ACE2 and its binding protein B0AT1 are involved in Trp-mediated alleviation of intestinal injury is largely unknown. Here, we used weaned piglets and IPEC-J2 cells as models and found that ACE2/B0AT1 alleviated lipopolysaccharide (LPS)-induced diarrhea and promoted intestinal barrier recovery via transport of Trp. The levels of the aryl hydrocarbon receptor (AhR) and mechanistic target of rapamycin (mTOR) pathways were altered by ACE2. Dietary Trp supplementation in LPS-treated weaned piglets revealed that Trp alleviated diarrhea by promoting ACE2/B0AT1 expression, and examination of intestinal morphology revealed that the damage to the intestinal barrier was repaired. Our study demonstrated that ACE2 accompanied by B0AT1 mediated the alleviation of diarrhea by Trp through intestinal barrier repair via the mTOR pathway.


Sujet(s)
Angiotensin-converting enzyme 2 , Diarrhée , Muqueuse intestinale , Lipopolysaccharides , Sérine-thréonine kinases TOR , Tryptophane , Animaux , Tryptophane/métabolisme , Angiotensin-converting enzyme 2/métabolisme , Sérine-thréonine kinases TOR/métabolisme , Suidae , Diarrhée/métabolisme , Muqueuse intestinale/métabolisme , Transduction du signal , Lignée cellulaire , COVID-19/métabolisme , Récepteurs à hydrocarbure aromatique/métabolisme , Récepteurs à hydrocarbure aromatique/génétique , SARS-CoV-2
17.
Front Aging Neurosci ; 16: 1395725, 2024.
Article de Anglais | MEDLINE | ID: mdl-38912522

RÉSUMÉ

Background: This randomized controlled trial aimed to compare the effects of butorphanol and sufentanil on early post-operative cognitive dysfunction (POCD) and systemic inflammation in older surgical patients. Methods: Patients (aged 65 years or above) undergoing surgeries with general anesthesia were randomized to either the butorphanol group (40 µg/kg during anesthesia induction) or the sufentanil group (0.4 µg/kg). Cognitive function changes during the perioperative period were assessed using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) scale up to 3 days after surgery. POCD was defined as a Z-score or composite Z-score greater than 1.96 for both MMSE and MoCA scores. Circulating inflammatory factors, including tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), and interleukin 10 (IL-10), were measured using enzyme-linked immunosorbent assay. Results: The study included 114 patients (median age: 71 years, 57.7% male). Compared to sufentanil, butorphanol significantly reduced the incidence of POCD on the first (11.5% versus 32.7%, p = 0.017) and third day (3.8% versus 15.4%, p = 0.046) after surgery. Additionally, patients receiving butorphanol had significantly lower circulating levels of TNF-α and IL-1ß at the time of discharge from the post-anesthesia care unit and on the first and third day after surgery (p < 0.05 for all comparisons). Furthermore, circulating IL-10 levels were significantly higher in patients receiving butorphanol (p < 0.05 for all comparisons). Conclusion: Administration of butorphanol during anesthesia induction, as opposed to sufentanil, was associated with a significant reduction in the early incidence of POCD in older surgical patients, possibly attributed to its impact on systemic inflammation.Clinical trial registration: The present study was registered in the China Clinical Trial Center (ChiCTR2300070805, 24/04/2023).

18.
J Mater Chem B ; 2024 Jun 25.
Article de Anglais | MEDLINE | ID: mdl-38915270

RÉSUMÉ

Postoperative adhesions, a prevalent complication following abdominal surgery, affect 90% of patients undergoing abdominal surgical procedures. Currently, the primary approach to prevent postoperative adhesions involves physical isolation of the surgical site and surrounding tissues using a hydrogel; however, this method represents a rudimentary strategy. Herein, considering the impact of oxidative stress and free radicals on postoperative adhesion during wound healing, an injectable antioxidant hydrogel, named PU-OHA-D, was successfully synthesized, which is formed by the crosslinking of dopamine-modified oxidized hyaluronic acid (OHA-D) and dihydrazide-terminated polyurethane (PU-ADH) through hydrazone bonding. PU-OHA-D hydrogel possesses versatile characteristics such as rapid gel formation, injectability, self-repair capability and biodegradability. Additionally, they exhibit an excellent ability to clear free radicals and superior tissue adhesion. PU-OHA-D can be injected in situ to form a hydrogel to prevent abdominal wall-cecum adhesion. Importantly, it can effectively eliminate free radicals and inhibit oxidative stress at the wound site. Thereby, it leads to collagen physiological degradation and prevents the occurrence of postoperative adhesions. The bioinspired hydrogel demonstrates its great potential in preventing postoperative adhesion and promoting wound healing.

19.
Sci Rep ; 14(1): 14338, 2024 06 21.
Article de Anglais | MEDLINE | ID: mdl-38906920

RÉSUMÉ

Previous research has produced inconsistent findings concerning the connection between metabolic syndrome and prostate cancer. It is challenging for observational studies to establish a conclusive causal relationship between the two. However, Mendelian randomization can provide stronger evidence of causality in this context. To examine the causal link between a metabolic composite and its components with prostate cancer, we performed a two-sample Mendelian randomization (MR) study utilizing aggregated data from genome-wide association studies, followed by meta-analyses. In our study, we employed inverse variance weighting as the primary method for MR analysis. Additionally, we assessed potential sources of heterogeneity and horizontal pleiotropy through the Cochran's Q test and MR-Egger regression. Moreover, we used multivariate MR to determine whether smoking versus alcohol consumption had an effect on the outcomes. We found no causal relationship between metabolic syndrome and its components and prostate cancer(MetS, odds ratio [OR] = 0.95, 95% confidence interval [CI] = 0.738-1.223, p = 0.691; TG, [OR] = 1.02, 95%[CI] = 0.96-1.08, p = 0.59); HDL, [OR] = 1.02, 95% [CI] = 0.97-1.07, p = 0.47; DBP, [OR] = 1.00, 95%[CI] = 0.99-1.01, p = 0.87; SBP, [OR] = 1.00, 95%[CI] = 0.99-1.00, p = 0.26; FBG [OR] = 0.92, 95%[CI] = 0.81-1.05, p = 0.23; WC, [OR] = 0.93, 95%[CI] = 0.84-1.03, p = 0.16). Finally, the MVMR confirms that the metabolic syndrome and its components are independent of smoking and alcohol consumption in prostate cancer. We didn't find significant evidence to determine a causal relationship between the metabolic syndrome and its components and prostate cancer through MR analysis. Further research is necessary to explore the potential pathogenesis between the two diseases.


Sujet(s)
Étude d'association pangénomique , Analyse de randomisation mendélienne , Syndrome métabolique X , Tumeurs de la prostate , Humains , Mâle , Consommation d'alcool/effets indésirables , Syndrome métabolique X/génétique , Odds ratio , Polymorphisme de nucléotide simple , Tumeurs de la prostate/génétique , Facteurs de risque , Fumer/effets indésirables
20.
Chem Commun (Camb) ; 60(55): 6977-6987, 2024 Jul 04.
Article de Anglais | MEDLINE | ID: mdl-38910536

RÉSUMÉ

Artificial intelligence (AI) offers transformative potential for chemical research through its ability to optimize reactions and processes, enhance energy efficiency, and reduce waste. AI-assisted chemical research (AI + chem) has become a global hotspot. To better understand the current research status of "AI + chem", this study conducted a scientific bibliometric investigation using CiteSpace. The web of science core collection was utilized to retrieve original articles related to "AI + chem" published from 2000 to 2024. The obtained data allowed for the visualization of the knowledge background, current research status, and latest knowledge structure of "AI + chem". The "AI + chem" has entered a stage of explosive growth, and the number of papers will maintain long-term high-speed growth. This article systematically analyzes the latest progress in "AI + chem" and objectively predicts future trends, including molecular design, reaction prediction, materials design, drug design, and quantum chemistry. The outcomes of this study will provide readers with a comprehensive understanding of the overall landscape of "AI + chem".

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