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Highland barley is a natural source for the development of phenolic compounds that exhibit potential in preventing type 2 diabetes, which is important for the agricultural and industrial utilization of highland barley. However, very few studies have focused on their effect on small intestinal absorption and barrier dysfunction, as well as the direct target for the modulation of hepatic glucose metabolism. In this study, procyanidin B1 (PB) and p-coumaric acid (CA) isolated from highland barley supplementation in impaired glucose tolerance (IGT) mice significantly increased lactase-phlorizin hydrolase (LPH), sulfotransferase 1A1 (SULT1A1), UDP glucuronosyltransferase 1A (UGT1A) families and sodium-dependent glucose transporter 1 (SGLT1) expression in the small intestine of IGT mice, indicating beneficial effects on polyphenol deglycosylation and transportation. Supplementation with PB and CA also exhibited attenuation of small intestinal barrier dysfunction by improving the mucus layer and tight junctions, which was closely related to the transportation of phenolic compounds. In addition, PB and CA supplementation were explored directly to bind to the insulin receptor and activate the insulin receptor substrate-1 (IRS-1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway, thereby modulating hepatic glucose metabolism and ameliorating hyperglycemic in IGT mice. These results offer crucial insights into the potential development of PB and CA as non-food nutraceuticals, as well as the extensive utilization of highland barley as an industrial crop.
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The objective of this work was to study the effects of heat-moisture treatment (HMT) of freshly harvested mature high-amylose maize (HAM) kernels on its starch structure, properties, and digestibility. Freshly harvested HAM kernels were sealed in Pyrex glass bottles and treated at 80 °C, 100 °C, or 120 °C. HMT of HAM kernels had no impact on its starch X-ray diffraction pattern but increased the relative crystallinity. This result together with the increased starch gelatinization temperatures and enthalpy change indicated starch molecules reorganization forming long-chain double-helical crystalline structure during HMT of HAM kernels. The aggregation of starch granules were observed after HMT, indicating interaction of starch granules and other components. This interaction and the high-temperature crystalline structure led to reductions in the starch digestibility, swelling power, solubility, and pasting viscosity of the HAM flours. Some starch granules remained intact and showed strong birefringence after the HAM flours were precooked at 100 °C for 20 min and followed by enzymatic hydrolysis, and the amount of undigested starch granules increased with increasing HMT temperatures. This result further supported that HMT of HAM kernels with high moisture level could increase the starch thermal stability and enzymatic resistance.
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Amilosa , Calor , Almidón , Zea mays , Zea mays/química , Amilosa/química , Almidón/química , Hidrólisis , Viscosidad , Solubilidad , Agua/química , Difracción de Rayos X , Harina/análisisRESUMEN
The objective of this study was to understand how the dynamic rheological behaviors of high-amylose wheat (HAW) dough during various heating stages measured using a mixolab were affected by the starch properties. At the heating stage of 30 °C - 90 °C, low minimum (C2) and peak (C3) torques were observed for HAW doughs, which resulted from their reduced starch granule swelling. During holding at 90 °C, HAW doughs had low minimum (C4) and C3 - C4 torques, indicating a good resistance to mechanical shear and endogenous enzyme degradation. HAW doughs also had low final (C5) and setback (C5 - C4) torques, consistent with their low starch swelling power and solubility. The increased amylose in HAW starch formed long-chain double-helical B-type polymorph and amylose-lipid complex, which resulted in high starch gelatinization-temperatures and enthalpy change, low swelling power and solubility, low pasting viscosity, and high resistance of swollen granules to mechanical shear and enzyme degradation. The overall patterns of dough-rheological behavior of HAW doughs during heating were similar to their respective starch pasting profiles, indicating that starch was the dominant contributor to the dough rheology during heating. This study provides useful information for food applications and manufacturing of HAW-based products, especially none-fermented products requiring firm texture and low viscosity.
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Amilosa , Reología , Almidón , Triticum , Amilosa/química , Triticum/química , Almidón/química , Viscosidad , Harina/análisis , Solubilidad , Calor , CalefacciónRESUMEN
Sensors designed based on the trans-cleavage activity of CRISPR/Cas12a systems have opened up a new era in the field of biosensing. The current design of CRISPR/Cas12-based sensors in the "on-off-on" mode mainly focuses on programming the activator strand (AS) to indirectly switch the trans-cleavage activity of Cas12a in response to target information. However, this design usually requires the help of additional auxiliary probes to keep the activator strand in an initially "blocked" state. The length design and dosage of the auxiliary probe need to be strictly optimized to ensure the lowest background and the best signal-to-noise ratio. This will inevitably increase the experiment complexity. To solve this problem, we propose using AS after the "RESET" effect to directly regulate the Cas12a enzymatic activity. Initially, the activator strand was rationally designed to be embedded in a hairpin structure to deprive its ability to activate the CRISPR/Cas12a system. When the target is present, target-mediated strand displacement causes the conformation change in the AS, the hairpin structure is opened, and the CRISPR/Cas12a system is reactivated; the switchable structure of AS can be used to regulate the degree of activation of Cas12a according to the target concentration. Due to the advantages of low background and stability, the CRISPR/Cas12a-based strategy can not only image endogenous biomarkers (miR-21) in living cells but also enable long-term and accurate imaging analysis of the process of exogenous virus invasion of cells. Release and replication of virus genome in host cells are indispensable hallmark events of cell infection by virus; sensitive monitoring of them is of great significance to revealing virus infection mechanism and defending against viral diseases.
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Técnicas Biosensibles , Sistemas CRISPR-Cas , MicroARNs , Sistemas CRISPR-Cas/genética , Técnicas Biosensibles/métodos , Humanos , MicroARNs/análisis , MicroARNs/metabolismo , Regulación Alostérica , Proteínas Asociadas a CRISPR/metabolismo , Endodesoxirribonucleasas/metabolismo , Endodesoxirribonucleasas/química , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Células HEK293RESUMEN
In recent years, the CRISPR/Cas12a-based sensing strategy has shown significant potential for specific target detection due to its rapid and sensitive characteristics. However, the "always active" biosensors are often insufficient to manipulate nucleic acid sensing with high spatiotemporal control. It remains crucial to develop nucleic acid sensing devices that can be activated at the desired time and space by a remotely applied stimulus. Here, we integrated photoactivation with the CRISPR/Cas12a system for DNA and RNA detection, aiming to provide high spatiotemporal control for nucleic acid sensing. By rationally designing the target recognition sequence, this photoactivation CRISPR/Cas12a system could recognize HPV16 and survivin, respectively. We combined the lateral flow assay strip test with the CRISPR/Cas12a system to realize the visualization of nucleic acid cleavage signals, displaying potential instant test application capabilities. Additionally, we also successfully realized the temporary control of its fluorescent sensing activity for survivin by photoactivation in vivo, allowing rapid detection of target nucleic acids and avoiding the risk of contamination from premature leaks during storage. Our strategy suggests that the CRISPR/Cas12a platform can be triggered by photoactivation to sense various targets, expanding the technical toolbox for precise biological and medical analysis. This study represents a significant advancement in nucleic acid sensing and has potential applications in disease diagnosis and treatment.
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Técnicas Biosensibles , Ácidos Nucleicos , Sistemas CRISPR-Cas/genética , Survivin/genética , Biomarcadores , Pruebas en el Punto de AtenciónRESUMEN
Post-stroke depression (PSD) is a prevalent mental health issue, and resveratrol (RES) has been implicated in its management. This study aimed to elucidate the impact of RES on PSD. A PSD rat model was established through middle cerebral artery occlusion and chronic unpredictable mild stress. Rats received RES via gavage, and depressive behaviors were evaluated through various measures. Cerebral infarction areas and brain tissue pathology were assessed using TTC and H&E staining. Levels of inflammatory factors (TNF-α/IL-1ß/IL-6/IL-10), neurotransmitters (ACH/DA/5-HT/BDNF), and oxidative stress-related indicators (SOD/GSH-Px/MDA), along with the total Nrf2/C-Nrf2/N-Nrf2/HO-1 proteins, were analyzed. The role of the Nrf2/HO-1 pathway was investigated by co-treating rats with RES and either an Nrf2 pathway specific inhibitor (ML385) or activator (dimethyl fumarate). PSD rats exhibited depressive behaviors, disrupted neurotransmitter levels, and oxidative stress markers. RES treatment effectively alleviated these symptoms and activated the Nrf2/HO-1 pathway in PSD rat brain tissues. Co-administration of ML385 attenuated the beneficial effects of RES in PSD rats. Altogether, RES mitigates depressive behaviors, improves cognitive dysfunction, and reduces oxidative stress and inflammatory response in PSD rats. These effects are mediated through the activation of the Nrf2/HO-1 pathway, suggesting RES as a potential therapeutic agent for PSD-related cognitive impairment.
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Depresión , Factor 2 Relacionado con NF-E2 , Ratas , Animales , Resveratrol/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Depresión/tratamiento farmacológico , Depresión/etiología , Estrés Oxidativo , Inflamación/tratamiento farmacológico , CogniciónRESUMEN
Interests in using high-amylose maize (HAM) flour and starch for low glycemic index foods continue to grow. The objective of this work was to understand resistant-starch formation during drying the HAM kernels. Freshly harvested HAM kernels with 28.2 % initial moisture were subjected to sun drying (~30 °C) or hot-air drying at 50 °C, 70 °C, 90 °C, or 110 °C. The enzymatic digestibility of HAM flour decreased from 63.6 % to 41.1 % as the drying temperature increased from 30 °C to 110 °C. The swelling power, solubility, and overall viscosity of HAM flours milled from kernels dried at 110 °C decreased, whereas the peak and conclusion gelatinization temperatures, enthalpy change, and relative crystallinity increased compared to those of flours from kernels dried at 30 °C, 50 °C, 70 °C, and 90 °C. Light microscopic and scanning electron microscopic images showed that starch granule aggregation in HAM flour increased with increasing drying-temperatures. The aggregates remained after 16 h enzymatic hydrolysis of cooked HAM flours. These results suggested that the increase of enzymatic resistance of HAM flour resulted from the formation of high temperature-resistant ordered structures in starch granules and the starch aggregates less accessible to enzymatic hydrolysis.
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Amilosa , Zea mays , Amilosa/química , Zea mays/química , Almidón Resistente , Almidón/química , Viscosidad , Harina/análisis , CalorRESUMEN
Rapid and highly effective removal of hexavalent chromium (Cr(â ¥)) is extremely vital to water resources restoration and environmental protection. To overcome the pH limitation faced by most ionic absorbents, an always positive covalent organic nanosheet (CON) material was prepared and its Cr(VI) adsorption and removal capability was investigated in detail. As-prepared EB-TFB CON (TFB = 1,3,5-benzaldehyde, EB = ethidium bromide) shows strong electropositivity in the tested pH range of 1 â¼ 10, display a pH-independent Cr(VI) removal ability, and work well for Cr(VI) pollution treatment with good anti-interference capability and reusability in a wide pH range covering almost all Cr(VI)-contaminated real water samples, thus eliminating the requirement for pH adjustment. Moreover, the nanosheet structure, which is obtained by a facile ultrasonic-assisted self-exfoliation, endows EB-TFB CON with fully exposed active sites and shortened mass transfer channels, and the Cr(VI) adsorption equilibrium can be reached within 15 min with a high adsorption capacity of 280.57 mg·g-1. The proposed Cr(VI) removal mechanism, which is attributed to the synergetic contributions of electrostatic adsorption, ion exchange and chemical reduction, is demonstrated by experiments and theoretical calculations. This work not only provides a general Cr(VI) absorbent without pH limitation, but also presents a paradigm to prepare ionic CONs with relatively constant surface charges.
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Lately, interest surrounding the utilization of plant-derived compounds as a viable beneficial approach for treating Alzheimer's disease (AD) has significantly increased. This study aimed to assess the defensive properties of rosavin against Alzheimer's disease induced by amyloid-ß, utilizing experimental models. We found that rosavin exhibited anti-aggregation and disaggregation properties, suggesting its potential to prevent the gathering of Aß-aggregates. In vitro experiments revealed that rosavin effectively mitigated the neurotoxicity induced by Aß in Neuro-2a cells, showcasing its protective potential. Rosavin significantly improved the Aß-induced cognitive deficits in Wistar rats, particularly in spatial memory. Which the pathophysiology of AD includes oxidative damage, which negatively impacts biological macromolecules. Triggers the apoptotic process, causing macromolecular destruction. Interestingly, rosavin attenuated Aß-induced macromolecular damages, thereby preserving neuronal integrity. Furthermore, the activation of antioxidative defense enzymes by rosavin inhibited oxidative damage. The positive outcomes associated with rosavin were primarily attributed to its capacity to enhance acetylcholine-mediated effects. Finally, rosavin has the potential to alleviate Aß-induced neurotoxicity and macromolecular damages, ultimately resulting in enhanced memorial and reasoning function in Wistar rats, offering promising prospects for the treatment of AD.
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Enfermedad de Alzheimer , Ratas , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/inducido químicamente , Ratas Wistar , Péptidos beta-Amiloides/toxicidad , Disacáridos/efectos adversos , Fragmentos de Péptidos/toxicidad , Modelos Animales de EnfermedadRESUMEN
INTRODUCTION: Interleukin-22 (IL-22) has been proven to exhibit a protective role in hepatic ischemia-reperfusion injury (HIRI). This study aimed to explore the change of IL-22 and IL-22 receptor 1 (IL-22R1) axis in HIRI and its role in mitochondrial apoptosis associated with STAT3 activation. MATERIALS AND METHODS: I/R mice were examined for the expression of IL-22, IL-22R1 and IL-22BP. The roles of IL-22 in hepatic histopathology and oxidative stress injuries (ALT, MDA and SOD) were determined. Oxidative stress damages of AML-12 cells were induced by H2O2, and were indicated by apoptosis, Ca2+ concentration, and mitochondrial function. The effects of IL-22 on p-STAT3Try705 were analyzed. RESULTS: We found that the expression of IL-22, IL-22R1, and IL-22BP was elevated 24 h after I/R induction, while decreased 48 h after I/R induction. Furthermore, we also discovered that IL-22 rescued the morphological damages and dysfunction of hepatocytes induced by H2O2, which were antagonized by IL-22BP, an endogenous antagonist of IL-22. Additionally, increased levels of Ca2+ concentration, MDA, ROS, apoptosis and mitochondrial dysfunction were noticed in H2O2-treated hepatocytes. However, IL-22 ameliorated the effects of I/R or H2O2. The protective effects of IL-22 were reversed by AG490, a specific antagonist of STAT3. CONCLUSIONS: In conclusion, our results indicated that IL-22 inhibited I/R-induced oxidative stress injury, Ca2+ overload, and mitochondrial apoptosis via STAT3 activation.
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Interleucina-22 , Daño por Reperfusión , Animales , Ratones , Ratas , Apoptosis , Peróxido de Hidrógeno/farmacología , Peróxido de Hidrógeno/metabolismo , Hígado/metabolismo , Mitocondrias/metabolismo , Estrés Oxidativo , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismoRESUMEN
BACKGROUND: The best choice between first-line aspiration and stent retriever for acute basilar artery occlusion remains controversial. This study aims to perform a systematic review and meta-analysis comparing the stent retriever and direct aspiration about reported recanalization rates and periprocedural complications. METHOD: PubMed, Embase, Web of Science, Cochrane, and Clinical Trials were searched for the studies evaluating the efficacy and safety of first-line aspiration versus stent retriever for acute basilar artery occlusion. A standard software program (Stata Corporation) was used for end-point analyses. Statistical significance was defined as a p-value less than .05. RESULTS: A total of 11 studies were involved in the current study, including 1014 patients. Regarding postoperative recanalization, the pooled analysis identified a significant difference in successful recanalization (odds ratio [OR] = 1.642; 95% confidence interval (95% CI): 1.099-2.453; p = .015) and complete recanalization (OR = 3.525; 95% CI: 1.306-2.872; p = .001) between the two groups in favor of the first-line aspiration. Concerning the complications, the first-line aspiration could achieve a lower rate of total complication (OR = .359; 95% CI: .229-.563; p < .001) and hemorrhagic complication (OR = .446, 95% CI: .259-.769; p = .004) than stent retriever. No significant difference was observed in postoperative mortality (OR = .966; p = .880), subarachnoid hematoma (OR = .171; p = .094), and parenchymal hematoma (OR = .799; p = .720). In addition, the pooled results revealed a significant difference in procedure duration between the two groups in favor of aspiration (WMD = -27.630, 95% CI: -50.958 to -4.302; p = .020). However, there was no significant difference in favorable outcome (OR = 1.149; p = .352) and rescue therapy (OR = 1.440; p = .409) between the two groups. CONCLUSION: Given that the first-line aspiration was associated with a higher rate of postoperative recanalization, a lower risk of postoperative complication, and a faster duration of the procedure, these findings support the aspiration may be more secure than a stent retriever.
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Arteriopatías Oclusivas , Procedimientos Endovasculares , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/terapia , Arteria Basilar/cirugía , Trombectomía/métodos , Resultado del Tratamiento , Stents , Procedimientos Endovasculares/métodos , Estudios RetrospectivosRESUMEN
A heteropore covalent organic framework incorporated silicone tube (S-tube@PDA@COF) was used as adsorbent to purify the matrices in vegetable extracts. The S-tube@PDA@COF was fabricated by a facile in-situ growth method and characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction and N2 adsorption-desorption. The as-prepared composite exhibited high removal efficiency of phytochromes and recovery (81.13-116.62%) of 15 chemical hazards from 5 representative vegetable samples. This study opens a promising avenue toward the facile synthesis of covalent organic frameworks (COFs)-derived silicone tubes for streamline operation in food sample pretreatment.
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PURPOSE: This study aims to investigate the clinical and molecular differences between diffuse large B-cell lymphoma (DLBCL) patients with MYD88L265P and MYD88other. METHODS: DLBCL patients with MYD88 variations were collected from the Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CHCAMS), and Suzhou Municipal Hospital from February 6th, 2007 to May 20th, 2022. Clinicopathological parameters and treatment outcomes between MYD88L265P and MYD88other were investigated. RESULTS: A total of 132 patients with MYD88 variations from a cohort of 475 DLBCL patients were included, among which, 78 were MYD88L265P, while 54 were MYD88other. MYD88L265P was more common in non-GCB subtype than MYD88other (83% vs. 60%, P = 0.004). Besides, MYD88L265P was significantly related to higher proportion of testicle/ central nervous system involvement (31% vs. 6%, P < 0.001), PIM1 mutation (71% vs. 39%, P < 0.001), and PIM1 hypermutation (28% vs. 11%, P = 0.018), compared with MYD88other. Compared with MYD88L265P, MYD88other were more likely to have higher percentage of advanced stage (60% vs. 42%, P = 0.044), extranodal site ≥ 2 (45% vs. 28%, P = 0.044), elevated LDH (55% vs. 35%, P = 0.033), positive CD10 expression (36% vs. 16%, P = 0.009), BCL-6 translocation (20% vs. 8%, P = 0.033), and NOTCH pathway gene alteration (24% vs. 13%, P = 0.040). In non-GCB DLBCL subtype, patients with MYD88other were significantly associated with worse progression free survival (PFS) than those with MYD88L265P when treated initially with R-CHOP/R-CHOP-like regimen (P = 0.010). CONCLUSION: The findings of this study indicate that DLBCL patients with MYD88L265P and MYD88other are likely to be two subgroups with different clinical and molecular characteristics. The survival of patients with MYD88other is not superior than those with MYD88L265P, even poorer when focusing on the non-GCB subtype.
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Linfoma de Células B Grandes Difuso , Factor 88 de Diferenciación Mieloide , Humanos , Pronóstico , Factor 88 de Diferenciación Mieloide/genética , Mutación , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Resultado del TratamientoRESUMEN
Objective: This study aimed to observe the diagnostic value of cranial magnetic resonance imaging (MRI) in patients with vascular dementia induced by ischemic stroke. Methods: The experiment was designed according to the randomized control principle. Two hundred and eighty patients with ischemic stroke who were admitted to Gucheng County Hospital between June 2019 and June 2021 were selected as research subjects. Patients without vascular dementia after stroke were included in the control group, and patients with vascular dementia after stroke were included in the observation group. The cranial MRI was performed in both groups. Result: Proportions of patients with large and moderate infarct lesions in brain tissues were significantly higher in the observation group than the control group. The data variation of relevant MRI detection indicators of the observation group was more obvious than that of the control group (P<0.05). The mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) scores of the observation group were lower than those of the control group (P<0.05), but the HIS score was higher (P>0.05). Patients with changes in brain morphology were more in the observation group than the control group (P<0.05). Conclusion: Patients with vascular dementia induced by ischemic stroke are characterized by cortical atrophy, widening of the cerebral sulcus, large infarct lesion area and sparse cerebral white matter. Cranial MRI can effectively identify these features. The application of cranial MRI has some clinical values for early treatment and prognostic assessment.
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Non-targeted analysis of chemical hazards in foods plays a crucial role in controlling food safety. However, because it brings forward high demand for sample pretreatment, materials suitable for the pretreatment of foods, especially animal foods, are rare. Herein, covalent organic frameworks (COF)-based monolithic materials were constructed by three successive steps: preparation of polydimethylsiloxane (PDMS) sponge using sugar cube as a sacrificial template, loading of a heteroporous COF on PDMS sponge via ultrasonic or in-situ growth method, coating of the obtained PDMS@COF by polydopamine (PDA) network. As-prepared PDMS@COF@PDA sponges were demonstrated to work well in sample pretreatment of animal foods for non-targeted analysis of chemical hazards. After a simple vortex treatment for about 2 min, more than 98% triglycerides, the main interfering matrix components in animal foods, could be removed from lard and pork samples, accompanied by "full recovery" (recovery efficiencies: ≥63%) of 44 chemical hazards with different physicochemical properties. Besides providing promising sample pretreatment materials for non-targeted food safety analysis, this work also paves a feasible way to improve COF-based monolithic materials and thus promote their practical applications, because we found that the introduction of PDA network on COF-based monolithic material surface could play a role in "killing three birds with one stone": enhancing the stability of the materials by overcoming the detachment of COF during operations; controllably adjusting hydrophobic and hydrogen-bonding interactions on the material surface to promote the removal of triglycerides; weakening the hydrophobic and π-π interactions between COF and chemical hazards to increase the recoveries of chemical hazards.
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Estructuras Metalorgánicas , Animales , Estructuras Metalorgánicas/química , AlimentosRESUMEN
Non-small cell lung cancer (NSCLC) overwhelmingly represents the predominant histological subtype of lung cancer, with lung adenocarcinoma emerging as the most prevalent form. Conventional Western medical treatments encompass a spectrum of modalities, including surgical interventions, cytotoxic chemotherapy, radiotherapy, targeted pharmacotherapy, and immunotherapy. In contrast, Traditional Chinese Medicine (TCM) methodologies encompass traditional Chinese medicine treatments, acupuncture therapies, and tuina treatments. While conventional Western medicine has made remarkable strides in the treatment of lung cancer, it is important to acknowledge the limitations inherent in singular treatment approaches. Consequently, the quest for a more comprehensive and integrative therapeutic paradigm becomes imperative. A deficiency of evaluation criteria specific to lung adenocarcinoma treatment in the realm of TCM represents an outstanding challenge in need of resolution. Nonetheless, in the backdrop of the continuous evolution of lung adenocarcinoma treatment modalities, the amalgamation of Chinese and Western medical approaches for treating this condition has exhibited a promising trajectory. It not only contributes to mitigating toxicity and augmenting efficacy but also serves to reduce a spectrum of postoperative complications, thereby enhancing the quality of patients' survival and extending life expectancy. This article furnishes a comprehensive survey of the research advancements in the integration of Chinese and Western medical approaches for treating lung adenocarcinoma. It elucidates the merits and demerits of individual and combined therapeutic strategies, surmounts current limitations, underscores the virtues of amalgamating Chinese and Western medical paradigms, and offers a more holistic, integrated, and efficacious treatment blueprint.
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Inflammation is one of the most crucial mechanism underlying hepatic ischemia-reperfusion injury (HIRI). Several studies have shown that Ac2-26, the active N-terminal peptide of Annexin A1, could modulate anti-inflammatory processes and protect the organs from ischemia-reperfusion injury (IRI). However the effects of Ac2-26 on an HIRI model have not been reported to date. The purpose of the present study was to determine whether Ac2-26 pretreatment could protect hepatocytes against acute HIRI by inhibiting neutrophil infiltration through regulation of the high mobility group box protein 1 (HMGB1)/Toll-like receptor 4 (TLR4)/NF-κB signaling pathway. To this end, a total of 72 adult C57BL/6 mice were randomly divided into sham operation (sham), ischemia-reperfusion (I/R), I/R + Ac2-26 and Ac2-26 groups. The HIRI model was established by occluding the branch of the hepatic pedicle to the left and median liver lobes with an atraumatic vascular clamp for 45 min, followed by reperfusion for 24 h. The expression of HMGB1, TLR4, NF-κB, IκBα and lymphocyte antigen 6 complex locus G6D (Ly6G) was detected using reverse transcription-quantitative PCR, western blotting and immunohistochemical staining; serum levels of HMGB1 were evaluated using an enzyme-linked immunosorbent assay. Flow cytometry was used to detect the proportion of neutrophil. The results indicated that Ac2-26 preconditioning rescued hepatocyte dysfunctions induced by HIRI. In addition, HIRI was associated with a significant increase in HMGB1 expression and release, accompanied by increased expression of TLR4, which was significantly inhibited by Ac2-26. Furthermore, the expression of phosphorylated (p)-NF-κB and the ratio of p-NF-κB to NF-κB were markedly increased, while the expression of IκBα was decreased in the I/R group compared with those in the sham group; however, these effects were reversed by Ac2-26 administration. Additionally, Ac2-26 administration significantly inhibited neutrophil infiltration and resulted in low levels of neutrophils and Ly6G as well as reduced myeloperoxidase activity. Taken together, these results indicated that Ac2-26 pretreatment serves a protective role against HIRI by regulating the HMGB1/TLR4/NF-κB signaling pathway and inhibiting neutrophil infiltration.
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Hepatic ischemia-reperfusion injury (HIRI) is one of the major sources of mortality and morbidity associated with hepatic surgery. Ac2-26, a short peptide of Annexin A1 protein, has been proved to have a protective effect against IRI. However, whether it exerts a protective effect on HIRI has not been reported. The HIRI mice model and the oxidative damage model of H2O2-induced AML12 cells were established to investigate whether Ac2-26 could alleviate HIRI by regulating the activation of IL-22/IL-22R1/STAT3 signaling. The protective effect of Ac2-26 was measured by various biochemical parameters related to liver function, apoptosis, inflammatory reaction, mitochondrial function and the expressions of IL-22, IL-22R1, p-STAT3Tyr705. We discovered that Ac2-26 reduced the Suzuki score and cell death rate, and increased the cell viability after HIRI. Moreover, we unraveled that Ac2-26 significantly decreased the number of apoptotic hepatocytes, and the expressions of cleaved-caspase-3 and Bax/Bcl-2 ratio. Furthermore, HIRI increased the contents of malondialdehyde (MDA), NADP+/NADPH ratio and reactive oxygen species (ROS), whereas Ac2-26 decreased them significantly. Additionally, Ac2-26 remarkably alleviated mitochondria dysfunction, which was represented by an increase in the adenosine triphosphate (ATP) content and mitochondrial membrane potential, a decrease in mitochondrial DNA (mtDNA) damage. Finally, we revealed that Ac2-26 pretreatment could significantly inhibit the activation of IL-22/IL22R1/STAT3 signaling. In conclusion, this work demonstrated that Ac2-26 ameliorated HIRI by reducing oxidative stress and inhibiting the mitochondrial apoptosis pathway, which might be closely related to the inhibition of the IL-22/IL22R1/STAT3 signaling pathway.
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Peróxido de Hidrógeno , Daño por Reperfusión , Animales , Ratones , Ratas , Peróxido de Hidrógeno/metabolismo , Hígado , Ratas Sprague-Dawley , Daño por Reperfusión/tratamiento farmacológico , Transducción de Señal , Anexina A2 , Fragmentos de Péptidos/farmacología , Interleucina-22RESUMEN
A nitrogen (N), oxygen (O)-rich porphyrin-based covalent organic framework (COF), in which interlayer porphyrin molecules are vertically stacked, is prepared and characterized. As-prepared N,O-rich TpTph COF shows a high adsorption capacity for Cd2+ due to the abundant coordination sites. More interesting, it is found that the formation of COF enlarges the porphyrin ring center space, thus facilitating the Cd2+coordination, and the resulting optical signal changes make the ratiometric detection of Cd2+ possible. Furthermore, using carbon fiber (CF) filaments, which are obtained from low cost and easy-to-obtain actived carbon mask, as support, porphyrin COF-based CF@TpTph membrane is prepared through in-situ growth of COF on the support followed by simple mechanical pressing. The CF@TpTph membrane is demonstrated to work well for both Cd2+ removal and enrichment from soil and water samples, and shows the advantages of ease of handling, robust stability, reduced secondary pollution risk to samples, and good reusability. This work provides a powerful tool for Cd2+ removal and enrichment, exhibits that preparing porphyrin-based COFs is a feasible way to promote the interactions between porphyrin ring and Cd2+, and demonstrates that mechanical pressing is a promising strategy for the design of COF-based monolithic materials to promote the practical applications of COFs.
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Estructuras Metalorgánicas , Porfirinas , Adsorción , Cadmio , Fibra de Carbono , Estructuras Metalorgánicas/química , Porfirinas/químicaRESUMEN
We propose an effective method for manufacturing human anatomical specimens in response to the shortage of cadaver specimens and the poor simulation results of anatomical specimen substitutes. Digital human data with high precision were used to create digital models and corresponding mapped textures. Different materials were chosen to print the digital models with full-color and multimaterial 3D-printing technology based on the histological characteristics of the anatomical structures. Anatomy experts and surgeons were then invited to compare the 3D printed models with authentic anatomical specimens in terms of morphological appearance, anatomical detail, and textural properties. The skull, brain, hand muscles, blood vessels and nerves of the hand, and the deep structure of the head and face were printed. The skull model used hard material, and the brain and hand muscles models used flexible and hard materials combined. The blood vessels, nerves of the hand, and the superficial and deep structure of the head and face used transparent materials, revealing the small vessels and nerves in the interior. In all the models, there were no significant differences from anatomical specimens in morphological appearance and anatomical detail. They also affected vision and touch in the same way as authentic specimens in the textural properties of color, roughness, smoothness, and fineness. Full-color and multi-material 3D printed anatomical models have the same visual and tactile properties as anatomical specimens and could serve to complement or supplement them in anatomy teaching to compensate for the shortage of cadavers.