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1.
Alzheimers Dement ; 20(7): 4583-4593, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38865281

RESUMEN

BACKGROUND: Mild cognitive impairment (MCI) heightens Alzheimer's disease (AD) risk, with diabetes mellitus (DM) potentially exacerbating this vulnerability. This study identifies the optimal intervention period and neurobiological targets in MCI to AD progression using the Alzheimer's Disease Neuroimaging Initiative dataset. METHODS: Analysis of 980 MCI patients, categorized by DM status, used propensity score matching and inverse probability treatment weighting to assess rate of conversion from MCI to AD, neuroimaging, and cognitive changes. RESULTS: DM significantly correlates with cognitive decline and an increased risk of progressing to AD, especially within the first year of MCI follow-up. It adversely affects specific brain structures, notably accelerating nucleus accumbens atrophy, decreasing gray matter volume and sulcal depth. DISCUSSION: Findings suggest the first year after MCI diagnosis as the critical window for intervention. DM accelerates MCI-to-AD progression, targeting specific brain areas, underscoring the need for early therapeutic intervention. HIGHLIGHTS: Diabetes mellitus (DM) accelerates mild cognitive impairment (MCI)-to-Alzheimer's disease (AD) progression within the first year after MCI diagnosis. DM leads to sharper cognitive decline within 12 months of follow-up. There is notable nucleus accumbens atrophy observed in MCI patients with DM. DM causes significant reductions in gray matter volume and sulcal depth. There are stronger correlations between cognitive decline and brain changes due to DM.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Progresión de la Enfermedad , Humanos , Disfunción Cognitiva/patología , Enfermedad de Alzheimer/patología , Masculino , Femenino , Anciano , Neuroimagen , Encéfalo/patología , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética , Atrofia/patología , Diabetes Mellitus , Anciano de 80 o más Años
2.
Pulm Pharmacol Ther ; 86: 102312, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38906321

RESUMEN

Acute lung injury (ALI) frequently occurs after video-assisted thoracoscopic surgery (VATS). Ferroptosis is implicated in several lung diseases. Therefore, the disparate effects and underlying mechanisms of the two commonly used anesthetics (sevoflurane (Sev) and propofol) on VATS-induced ALI need to be clarified. In the present study, enrolled patients were randomly allocated to receive Sev (group S) or propofol anesthesia (group P). Intraoperative oxygenation, morphology of the lung tissue, expression of ZO-1, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), superoxide dismutase (SOD), glutathione (GSH), Fe2+, glutathione peroxidase 4 (GPX4), and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in the lung tissue as well as the expression of TNF-α and IL-6 in plasma were measured. Postoperative complications were recorded. Of the 85 initially screened patients scheduled for VATS, 62 were enrolled in either group S (n = 32) or P (n = 30). Compared with propofol, Sev substantially (1) improved intraoperative oxygenation; (2) relieved histopathological lung injury; (3) increased ZO-1 protein expression; (4) decreased the levels of TNF-α and IL-6 in both the lung tissue and plasma; (5) increased the contents of GSH and SOD but decreased Fe2+ concentration; (6) upregulated the protein expression of p-AKT, Nrf2, HO-1, and GPX4. No significant differences in the occurrence of postoperative outcomes were observed between both groups. In summary, Sev treatment, in comparison to propofol anesthesia, may suppress local lung and systemic inflammatory responses by activating the PI3K/Akt/Nrf2/HO-1 pathway and inhibiting ferroptosis. This cascade of effects contributes to the maintenance of pulmonary epithelial barrier permeability, alleviation of pulmonary injury, and enhancement of intraoperative oxygenation in patients undergoing VATS.

3.
J Nat Prod ; 87(6): 1660-1665, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38888514

RESUMEN

Chetocochliodin M (5) containing a rare cage-ring and chetocochliodin N (6) featuring an unusual piperazine-2,3-dione ring system together with known analogues chetomin (1), chetoseminudin C (2), chetocochliodin I (3), and oidioperazine E (4) were targeted for purification from the fungus Chaetomium cochliodes using a UPLC-Q-TOF-MS/MS approach. The structures of the new compounds were elucidated using HR-ESI-MS, NMR, and ECD spectra. Compounds 1, 3, and 6 exhibited strong cytotoxic activities against A549 and HeLa cancer cell lines.


Asunto(s)
Chaetomium , Espectrometría de Masas en Tándem , Chaetomium/química , Humanos , Estructura Molecular , Espectrometría de Masas en Tándem/métodos , Células HeLa , Cromatografía Líquida de Alta Presión/métodos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Ensayos de Selección de Medicamentos Antitumorales , Células A549 , Piperazinas/farmacología , Piperazinas/química , Piperazinas/aislamiento & purificación
4.
Nat Commun ; 15(1): 3008, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38589420

RESUMEN

The construction of functional three-dimensional covalent organic frameworks (3D COFs) for gas separation, specifically for the efficient removal of ethane (C2H6) from ethylene (C2H4), is significant but challenging due to their similar physicochemical properties. In this study, we demonstrate fine-tuning the pore environment of ultramicroporous 3D COFs to achieve efficient one-step C2H4 purification. By choosing our previously reported 3D-TPB-COF-H as a reference material, we rationally design and synthesize an isostructural 3D COF (3D-TPP-COF) containing pyridine units. Impressively, compared with 3D-TPB-COF-H, 3D-TPP-COF exhibits both high C2H6 adsorption capacity (110.4 cm3 g-1 at 293 K and 1 bar) and good C2H6/C2H4 selectivity (1.8), due to the formation of additional C-H···N interactions between pyridine groups and C2H6. To our knowledge, this performance surpasses all other reported COFs and is even comparable to some benchmark porous materials. In addition, dynamic breakthrough experiments reveal that 3D-TPP-COF can be used as a robust absorbent to produce high-purity C2H4 directly from a C2H6/C2H4 mixture. This study provides important guidance for the rational design of 3D COFs for efficient gas separation.

5.
J Am Chem Soc ; 2024 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-38615324

RESUMEN

The development of novel soft porous crystals (SPCs) that can be transformed from nonporous to porous crystals is significant because of their promising applications in gas storage and separation. Herein, we systematically investigated for the first time the gas-triggered gate-opening behavior of three-dimensional covalent organic frameworks (3D COFs) with flexible building blocks. FCOF-5, a 3D COF containing C-O single bonds in the backbone, exhibits a unique "S-shaped" isotherm for various gases, such as CO2, C2, and C3 hydrocarbons. According to in situ characterization, FCOF-5 undergoes a pressure-induced closed-to-open structural transition due to the rotation of flexible C-O single bonds in the framework. Furthermore, the gated hysteretic sorption property of FCOF-5 can enable its use as an absorbent for the efficient removal of C3H4 from C3H4/C3H6 mixtures. Therefore, 3D COFs synthesized from flexible building blocks represent a new type of SPC with gate-opening characteristics. This study will strongly inspire us to design other 3D COF-based SPCs for interesting applications in the future.

7.
Biomed Pharmacother ; 170: 116028, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38113627

RESUMEN

Klebsiella pneumoniae (Kpn) is an important pathogen of hospital-acquired pneumonia, which can lead to sepsis and death in severe cases. In this study, we simulated pneumonia induced by Kpn infection in mice to investigate the therapeutic effect of naringin (NAR) on bacterial-induced lung inflammation. Mice infected with Kpn exhibited increases in white blood cells (WBC) and neutrophils in the peripheral blood and pathological severe injury of the lungs. This injury was manifested by increased expression of the inflammatory cytokines interleukin (IL)- 18, IL-1ß, tumor necrosis factor-α (TNF-α) and IL-6, and elevated the expression of NLRP3 protein. NAR treatment could decrease the protein expression of NLRP3, alleviate lung inflammation, and reduce lung injury in mice caused by Kpn. Meanwhile, molecular docking results suggest NAR could bind to NLRP3 and Surface Plasmon Resonance (SPR) analyses also confirm this result. In vitro trials, we found that pretreated with NAR not only inhibited nuclear translocation of nuclear factor (NF)-κB protein P65 but also attenuated the protein interaction of NLRP3, caspase-1 and ASC and inhibited the assembly of NLRP3 inflammasome in mice AMs. Additionally, NAR could reduce intracellular potassium (K+) efflux, inhibiting NLRP3 inflammasome activation. These results indicated that NAR could protect against Kpn-induced pneumonia by inhibiting the overactivation of the NLRP3 inflammasome signaling pathway. The results of this study confirm the efficacy of NAR in treating bacterial pneumonia, refine the mechanism of action of NAR, and provide a theoretical basis for the research and development of NAR as an anti-inflammatory adjuvant.


Asunto(s)
Inflamasomas , Neumonía , Ratones , Animales , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Klebsiella pneumoniae , Simulación del Acoplamiento Molecular , FN-kappa B/metabolismo , Neumonía/tratamiento farmacológico
8.
Heliyon ; 9(10): e20405, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37780755

RESUMEN

Anesthesiologists are often faced with patients combined with a series of organ injuries, such as acute lung injury, myocardial ischemia-reperfusion injury, and neurodegenerative diseases. With the in-depth study of these diseases, we are more aware of the choice and rational use of anesthetics for the prognosis of these patients. Ferroptosis is a new type of programmed cell death. This unique pattern of cell death, driven by an imbalance between oxides and antioxidants, is regulated by multiple cellular metabolic events, including redox homeostasis, iron handling, mitochondrial activity, and lipids peroxidation. Numerous studies confirmed that anesthetics modulate ferroptosis by interfering its machineries such as cystine-import-glutathione-glutathione peroxidase 4 axis, Heme oxygenase 1, nuclear factor erythroid 2-related factor 2, and iron homeostasis system. In this literature review, we systemically illustrated possible involvement of ferroptosis in effects of anesthetics and adjuvant drugs on multiple organ diseases, hoping our work may serve as a basis for further studies on regulating ferroptosis through anesthetics related pharmacological modulation and promoting the rational use of anesthetics.

9.
J Am Chem Soc ; 145(41): 22329-22334, 2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37792489

RESUMEN

The limited structural diversity of three-dimensional covalent organic frameworks (3D COFs) greatly restricts their application exploration. Therefore, there is an urgent need to expand their library of molecular building blocks, such as the development of highly connected (>4 reaction sites) polyhedral nodes. Herein, by precisely controlling the precursor conformation, we rationally designed a new 6-connected triangular prism node derived from the triphenylbenzene molecule and further used it to construct a novel 3D COF (3D-TMTAPB-COF) via imine condensation reaction. Surprisingly, without the addition of competing reagents, 3D-TMTAPB-COF crystallized directly into single crystals of ∼15 µm in size and was determined to adopt a rare 6-fold interpenetrated (Class IIIa interpenetration) acs topology. In addition, 3D-TMTAPB-COF showed a high SF6 adsorption capacity (60.9 cm3 g-1) and good SF6/N2 selectivity (335) at 298 K and 1 bar, superior to those of most crystalline porous materials. This work not only confirms the possibility of growing large-size single-crystal 3D COFs formed with strong covalent bonds by a solvothermal method in the absence of modulators, but also reports a novel triangular prism node for future construction of 3D COFs with interesting applications.

10.
Surg Endosc ; 37(12): 9217-9227, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37872426

RESUMEN

BACKGROUND: Postoperative nausea and vomiting (PONV) is a common and distressing complication of laparoscopic bariatric surgery (LBS). However, there is a lack of effective integrated prediction models for preventing and treating PONV in patients after LBS. METHODS: Based on a randomized controlled trial conducted between November 1, 2021, and May 13, 2022, we included 334 participants who underwent LBS according to the inclusion criteria. The database was divided randomly into training and validation cohorts in a ratio of 7:3. Least absolute shrinkage and selection operator plus multivariable logistic regression were used to identify independent predictors and construct a nomogram. The performance of the nomogram was assessed and validated by the area under the receiver operating characteristic curve (AUC), the concordance index (C-index), calibration plots, and a decision curve analysis (DCA). We also explored specific risk factors for PONV in patients with diabetes. RESULTS: The subjects were divided randomly into training (n = 234) and validation (n = 100) cohorts. Age, history of diabetes, type of surgery, and sugammadex use were incorporated to construct a nomogram prediction model. In the training cohort, the AUC and the optimism-corrected C-index were 0.850 [95% confidence interval (CI) 0.801-0.899] and 0.848, while in the validation cohort they were 0.847 (95% CI 0.768-0.925) and 0.844, respectively. The calibration plots showed good agreement between the predicted and actual observations. The DCA results demonstrated that the nomogram was clinically useful. The type of surgery, sugammadex use, and insulin level at 120 min were predictors of PONV in patients with diabetes with an AUC of 0.802 (95% CI 0.705-0.898). CONCLUSIONS: We developed and validated a prediction model for PONV in patients after LBS. A risk factor analysis of PONV in patients with diabetes provides clinicians with a more precise prophylactic protocol.


Asunto(s)
Cirugía Bariátrica , Diabetes Mellitus , Laparoscopía , Humanos , Cirugía Bariátrica/efectos adversos , Laparoscopía/efectos adversos , Nomogramas , Náusea y Vómito Posoperatorios/epidemiología , Náusea y Vómito Posoperatorios/etiología , Sugammadex , Ensayos Clínicos Controlados Aleatorios como Asunto
11.
J Vis Exp ; (198)2023 08 18.
Artículo en Inglés | MEDLINE | ID: mdl-37607103

RESUMEN

Pericytes are crucial mural cells situated within cerebral microcirculation, pivotal in actively modulating cerebral blood flow via contractility adjustments. Conventionally, their contractility is gauged by observing morphological shifts and nearby capillary diameter changes under specific circumstances. Yet, post-tissue fixation, evaluating vitality and ensuing pericyte contractility of imaged brain pericytes becomes compromised. Similarly, genetically labeling brain pericytes falls short in distinguishing between viable and non-viable pericytes, particularly in neurologic conditions like subarachnoid hemorrhage (SAH), where our preliminary investigation validates brain pericyte demise. A reliable protocol has been devised to surmount these constraints, enabling simultaneous fluorescent tagging of both functional and non-functional brain pericytes in brain sections. This labeling method allows high-resolution confocal microscope visualization, concurrently marking the brain slice microvasculature. This innovative protocol offers a means to appraise brain pericyte contractility, its impact on capillary diameter, and pericyte structure. Investigating brain pericyte contractility within the SAH context yields insightful comprehension of its effects on cerebral microcirculation.


Asunto(s)
Hemorragia Subaracnoidea , Humanos , Pericitos , Encéfalo , Diagnóstico por Imagen , Circulación Cerebrovascular
12.
J Am Chem Soc ; 145(34): 18737-18741, 2023 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-37584696

RESUMEN

Herein, we report the introduction of steric hindrance in molecular building blocks to prevent π···π stacking, thus allowing two-dimensional (2D) covalent organic sheets to form three-dimensional (3D) covalent organic frameworks (COFs) through entanglement. Starting from the rationally designed precursors containing a bulky anthracene unit in the vertical direction, a highly crystalline COF (3D-An-COF) was successfully synthesized. Very interestingly, 3D-An-COF was determined as an entangled 2D square net (sql) structure, and the high-resolution data (1.1 Å) obtained by the continuous rotation electron diffraction technique allowed us to directly locate all non-hydrogen atoms. Structurally, the presence of an anthracene group outside the C2h symmetry plane strongly reduces the π···π interactions and promotes the formation of square entanglements. In addition, 3D-An-COF is fluorescent and can be used as a sensor to detect the trace amount of antibiotics in water. This study provides a new strategy for the structural diversification of 3D COFs and will certainly motivate us to construct more entangled COFs for interesting applications in the future.

13.
Mol Med Rep ; 28(3)2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37449526

RESUMEN

Adipose tissue­derived mesenchymal stem cells (ADMSCs) differentiate into cardiomyocytes and may be an ideal cell source for myocardial regenerative medicine. Ghrelin is a gastric­secreted peptide hormone involved in the multilineage differentiation of MSCs. To the best of our knowledge, however, the role and potential downstream regulatory mechanism of ghrelin in cardiomyocyte differentiation of ADMSCs is still unknown. The mRNA and protein levels were measured by reverse transcription­quantitative PCR and western blotting. Immunofluorescence staining was used to show the expression and cellular localization of cardiomyocyte markers and ß­catenin. RNA sequencing was used to explore the differentially expressed genes (DEGs) that regulated by ghrelin. The present study found that ghrelin promoted cardiomyocyte differentiation of ADMSCs in a concentration­dependent manner, as shown by increased levels of cardiomyocyte markers GATA binding protein 4, α­myosin heavy chain (α­MHC), ISL LIM homeobox 1, NK2 homeobox 5 and troponin T2, cardiac type. Ghrelin increased ß­catenin accumulation in nucleus and decreased the protein expression of secreted frizzled­related protein 4 (SFRP4), an inhibitor of Wnt signaling. RNA sequencing was used to determine the DEGs regulated by ghrelin. Functional enrichment showed that DEGs were more enriched in cardiomyocyte differentiation­associated terms and Wnt pathways. Dead­box helicase 17 (DDX17), an upregulated DEG, showed enhanced mRNA and protein expression levels following ghrelin addition. Overexpression of DDX17 promoted protein expression of cardiac­specific markers and ß­catenin and enhanced the fluorescence intensity of α­MHC and ß­catenin. DDX17 upregulation inhibited protein expression of SFRP4. Rescue assay confirmed that the addition of SFRP4 partially reversed ghrelin­enhanced protein levels of cardiac­specific markers and the fluorescence intensity of α­MHC. In conclusion, ghrelin promoted cardiomyocyte differentiation of ADMSCs by DDX17­mediated regulation of the SFRP4/Wnt/ß­catenin axis.


Asunto(s)
Células Madre Mesenquimatosas , Miocitos Cardíacos , Miocitos Cardíacos/metabolismo , Ghrelina/farmacología , Ghrelina/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Diferenciación Celular/genética , Células Madre Mesenquimatosas/metabolismo , Vía de Señalización Wnt , ARN Mensajero/metabolismo
14.
Int J Ophthalmol ; 16(7): 1100-1109, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37465514

RESUMEN

AIM: To compare the macular ganglion cell-inner plexiform layer (GCIPL) thickness, retinal nerve fiber layer (RNFL) thickness, optic nerve head (ONH) parameters, and retinal vessel density (VD) measured by spectral-domain optical coherence tomography (SD-OCT) and analyze the correlations between them in the early, moderate, severe primary angle-closure glaucoma (PACG) and normal eyes. METHODS: Totally 70 PACG eyes and 20 normal eyes were recruited for this retrospective analysis. PACG eyes were further separated into early, moderate, or severe PACG eyes using the Enhanced Glaucoma Staging System (GSS2). The GCIPL thickness, RNFL thickness, ONH parameters, and retinal VD were measured by SD-OCT, differences among the groups and correlations within the same group were calculated. RESULTS: The inferior and superotemporal sectors of the GCIPL thickness, rim area of ONH, average and inferior sector of the retinal VD were significantly reduced (all P<0.05) in the early PACG eyes compared to the normal and the optic disc area, cup to disc ratio (C/D), and cup volume were significantly higher (all P<0.05); but the RNFL was not significant changes in early and moderate PACG. In severe group, the GCIPL and RNFL thickness were obvious thinning with retinal VD were decreasing as well as C/D and cup volume increasing than other three groups (all P<0.01). In the early PACG subgroup, there were significant positive correlations between retinal VD and GCIPL thickness (except superonasal and inferonasal sectors, r=0.573 to 0.641, all P<0.05), superior sectors of RNFL thickness (r=0.055, P=0.049). More obvious significant positive correlations were existed in moderate PACG eyes between retinal VD and superior sectors of RNFL thickness (r=0.650, P=0.022), and temporal sectors of RNFL thickness (r=0.740, P=0.006). In the severe PACG eyes, neither GCIPL nor RNFL thickness was associated with retinal VD. CONCLUSION: The ONH damage and retinal VD loss appears earlier than RNFL thickness loss in PACG eyes. As the PACG disease progressed from the early to the moderate stage, the correlations between the retinal VD and RNFL thickness increases.

16.
Nat Med ; 29(6): 1424-1436, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37280275

RESUMEN

Gemcitabine plus cisplatin (GP) chemotherapy is the standard of care for nasopharyngeal carcinoma (NPC). However, the mechanisms underpinning its clinical activity are unclear. Here, using single-cell RNA sequencing and T cell and B cell receptor sequencing of matched, treatment-naive and post-GP chemotherapy NPC samples (n = 15 pairs), we show that GP chemotherapy activated an innate-like B cell (ILB)-dominant antitumor immune response. DNA fragments induced by chemotherapy activated the STING type-I-interferon-dependent pathway to increase major histocompatibility complex class I expression in cancer cells, and simultaneously induced ILB via Toll-like receptor 9 signaling. ILB further expanded follicular helper and helper type 1 T cells via the ICOSL-ICOS axis and subsequently enhanced cytotoxic T cells in tertiary lymphoid organ-like structures after chemotherapy that were deficient for germinal centers. ILB frequency was positively associated with overall and disease-free survival in a phase 3 trial of patients with NPC receiving GP chemotherapy ( NCT01872962 , n = 139). It also served as a predictor for favorable outcomes in patients with NPC treated with GP and immunotherapy combined treatment (n = 380). Collectively, our study provides a high-resolution map of the tumor immune microenvironment after GP chemotherapy and uncovers a role for B cell-centered antitumor immunity. We also identify and validate ILB as a potential biomarker for GP-based treatment in NPC, which could improve patient management.


Asunto(s)
Cisplatino , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/patología , Cisplatino/uso terapéutico , Gemcitabina , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/etiología , Neoplasias Nasofaríngeas/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Desoxicitidina/uso terapéutico , Microambiente Tumoral
17.
Pharmaceuticals (Basel) ; 16(6)2023 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-37375842

RESUMEN

The activity of polysaccharides is usually related to molecular weight. The molecular weight of polysaccharides is critical to their immunological effect in cancer therapy. Herein, the Codonopsis polysaccharides of different molecular weights were isolated using ultrafiltration membranes of 60- and 100-wDa molecular weight cut-off to determine the relationship between molecular weight and antitumor activities. First, three water-soluble polysaccharides CPPS-I (<60 wDa), CPPS-II (60-100 wDa), and CPPS-III (>100 wDa) from Codonopsis were isolated and purified using a combination of macroporous adsorption resin chromatography and ultrafiltration. Their structural characteristics were determined through chemical derivatization, GPC, HPLC, FT-IR, and NMR techniques. In vitro experiments indicated that all Codonopsis polysaccharides exhibited significant antitumor activities, with the tumor inhibition rate in the following order: CPPS-II > CPPS-I > CPPS-III. The treatment of CPPS-II exhibited the highest inhibition rate at a high concentration among all groups, which was almost as efficient as that of the DOX·HCL (10 µg/mL) group at 125 µg/mL concentration. Notably, CPPS-II demonstrated the ability to enhance NO secretion and the antitumor ability of macrophages relative to the other two groups of polysaccharides. Finally, in vivo experiments revealed that CPPS-II increased the M1/M2 ratio in immune system regulation and that the tumor inhibition effect of CPPS-II + DOX was superior to that of DOX monotherapy, implying that CPPS-II + DOX played a synergistic role in regulating the immune system function and the direct tumor-killing ability of DOX. Therefore, CPPS-II is expected to be applied as an effective cancer treatment or adjuvant therapy.

18.
J Bioenerg Biomembr ; 55(3): 195-205, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37237241

RESUMEN

Adipose tissue-derived mesenchymal stem cells (ADSCs) have promising effects on nerve repair due to the differentiation ability to neural cells. Ghrelin has been shown to promote the neural differentiation of ADSCs. This work was designed to explore its underlying mechanism. Herein, we found high expression of LNX2 in ADSCs after neuronal differentiation. Knockdown of LNX2 might block neuronal differentiation of ADSCs, as evidenced by the decreased number of neural-like cells and dendrites per cell, and the reduced expressions of neural markers (including ß-Tubulin III, Nestin, and MAP2). We also demonstrated that LNX2 silencing suppressed the nuclear translocation of ß-catenin in differentiated ADSCs. Luciferase reporter assay indicated that LNX2 inhibited wnt/ß-catenin pathway by reducing its transcriptional activity. In addition, results showed that LNX2 expression was increased by ghrelin, and its inhibition diminished the effects of ghrelin on neuronal differentiation. Altogether, the results suggest that LNX2 is involved in the role of ghrelin to facilitate neuronal differentiation of ADSCs.


Asunto(s)
Ghrelina , Células Madre Mesenquimatosas , beta Catenina , beta Catenina/metabolismo , Diferenciación Celular/fisiología , Células Cultivadas , Ghrelina/farmacología , Ghrelina/metabolismo , Células Madre Mesenquimatosas/metabolismo , Neuronas/metabolismo , Humanos
19.
BMC Anesthesiol ; 23(1): 163, 2023 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-37189069

RESUMEN

BACKGROUND: Postoperative nausea and vomiting (PONV) is a common but troublesome complication in patients who undergo laparoscopic bariatric surgery (LBS). Whether sugammadex use is related to the persistent decrease in the occurrence of PONV during postoperative inpatient hospitalization, which is critical for the rehabilitation of patients after LBS, remains unknown. METHODS: The study was based on a randomized controlled trial conducted in an accredited bariatric centre. A total of 205 patients who underwent LBS were included in the analysis. Univariate analysis and multivariable logistic regression model were used to identify the significant variables related to PONV. Then propensity score matching and inverse probability of treatment weighting (IPTW) were employed to compare outcomes between the sugammadex and neostigmine groups. The primary outcome was the incidence of PONV within 48 h after LBS. The secondary endpoints included the severity of PONV, time to first flatus, need for rescue antiemetic therapy, and water intake. RESULTS: The incidence of PONV was 43.4% (89/205) within the first 48 h after LBS. In multivariable analysis, sugammadex use (OR 0.03, 95% CI 0.01-0.09, P < 0.001) was an independent protective factor of PONV. After IPTW adjustment, sugammadex use was associated with lower incidence of PONV (OR 0.54, 95% CI 0.48-0.61, P < 0.001), postoperative nausea (PON) (OR 0.77, 95% CI 0.67-0.88, P < 0.001), and postoperative vomiting (POV) (OR 0.60, 95% CI 0.53-0.68, P < 0.001) within postoperative 48 h. The severity of PON as well as the incidence and severity of POV within the first 24 h were also lower in the sugammadex group (all P < 0.05). Reduced need for rescue antiemetic therapy within the first 24 h, increased water intake for both periods, and earlier first passage of flatus were observed in the sugammadex group (all P < 0.05). CONCLUSIONS: Compared with neostigmine, sugammadex can reduce the incidence and severity of PONV, increase postoperative water intake, and shorten the time to first flatus in bariatric patients during postoperative inpatient hospitalization, which may play a pivotal role in enhanced recovery. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100052418, http://www.chictr.org.cn/showprojen.aspx?proj=134893 , date of registration: October 25, 2021).


Asunto(s)
Antieméticos , Cirugía Bariátrica , Laparoscopía , Obesidad , Sugammadex , Adulto , Humanos , Antieméticos/uso terapéutico , Cirugía Bariátrica/efectos adversos , Flatulencia/inducido químicamente , Flatulencia/tratamiento farmacológico , Incidencia , Neostigmina , Obesidad/complicaciones , Náusea y Vómito Posoperatorios/inducido químicamente
20.
J Am Chem Soc ; 145(20): 11276-11281, 2023 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-37167629

RESUMEN

Dimensional isomers, defined in reticular chemistry as frameworks consisting of identical molecular building blocks but extended in two or three dimensions (2D or 3D), are an important type of framework isomers that have never been isolated. Herein, we report the crystallization of dimensional isomers in covalent organic frameworks (COFs) for the first time. By polymerization of the same molecular building blocks at different temperatures, both 2D and 3D COFs were successfully constructed due to the temperature-induced conformational changes of precursors from planar to tetrahedral. In addition, the non-fluorescent 2D COF can be gradually converted into the fluorescent 3D COF by increasing the temperature under solvothermal conditions. Therefore, it is reasonable to crystallize the dimensional isomers of reticular materials by controlling the conformation of molecular building blocks, and more examples can be expected. Since the obtained dimensional isomers show different properties and functions, this work will definitely motivate us to design reticular materials for target applications in the future.

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