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1.
World J Gastroenterol ; 30(2): 158-169, 2024 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-38312121

RESUMO

BACKGROUND: Tumor budding (TB) has emerged as a promising independent prognostic biomarker in colorectal cancer (CRC). The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC. However, existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies. Consequently, this study investigated the correlation among TB categories, clinicopathological features, and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification. AIM: To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC. METHODS: The clinical data of 547 CRC patients were collected for this retrospective study. Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines. RESULTS: Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy (P = 0.004), clinical stage IV (P < 0.001), ≥ 4 regional lymph node metastases (P = 0.004), left-sided colonic cancer (P = 0.040), and Bd 2-3 (P = 0.002) were independent prognostic factors in patients with stage III-IV CRC. Moreover, the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3, both in the tumor stroma and its invasive margin. CONCLUSION: TB has an independent predictive prognostic value in patients with stage III-IV CRC. It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Humanos , Prognóstico , Estudos Retrospectivos , Estadiamento de Neoplasias , Neoplasias Colorretais/patologia , Neoplasias do Colo/patologia
2.
J Chem Theory Comput ; 20(3): 1386-1397, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38300767

RESUMO

The embedded cluster method has been used extensively in the study of the chemical and physical properties of metal oxides. This method has been a popular tool due to its relatively high accuracy and low computational cost. An even more promising option may entail integrating the embedded cluster method with the combined quantum mechanical and molecular mechanical (QM/MM) approach, thereby enabling further consideration of interactions within the entire system for superior results. We aim to accurately model the chemistry of metal oxides using this combined scheme. Here, using the prototypical MgO(100) surface as a test system, with Mg9O14 as the cluster in the quantum mechanical region, we show that the embedded cluster with untailored boundary effective core potentials (ECPs) can have frontier orbital energy levels that substantially deviate from the quantum mechanical reference results. This occurs even when Mg9O9, which retains the stoichiometry of MgO, is used as the cluster in the quantum mechanical region. As a result, the chemical properties of the embedded cluster models differ from those of the quantum mechanical reference model. To address this issue, we propose a new variant of the embedded cluster method called the level-shifted embedded cluster (LSEC) method, which allows the energy levels to be shifted to match the reference levels by tuning the boundary ECPs. Our validation calculations on the adsorption of various adsorbates with different properties on the MgO(100) surface show that the overall performance of QM/MM with the LSEC method is excellent for the adsorption energies, geometries, and charge properties. The excellent performance holds for both the nonstoichiometric and stoichiometric clusters (i.e., Mg9O14 and Mg9O9, respectively), demonstrating the robustness of the LSEC method. We expect that the LSEC method can be combined with QM/MM or used separately for future chemical studies of metal oxides and other ionically bonded systems.

3.
Int J Surg ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38348834

RESUMO

BACKGROUNDS: The effectiveness of procalcitonin-based algorithms in guiding antibiotic usage for febrile acute necrotizing pancreatitis (ANP) remains controversial. Metagenomic next-generation sequencing (mNGS) has been applied to diagnose infectious diseases. We aimed to evaluate the effectiveness of blood mNGS in guiding antibiotic stewardship for febrile ANP. MATERIALS AND METHODS: The prospective multicenter clinical trial was conducted at seven hospitals in China. Blood samples were collected during fever (T ≥38.5°C) from ANP patients. The effectiveness of blood mNGS, procalcitonin, and blood culture in diagnosing pancreatic infection was evaluated and compared. Additionally, the real-world utilization of antibiotics and the potential mNGS-guided antimicrobial strategy in febrile ANP were also analyzed. RESULTS: From May 2023 to October 2023, a total of 78 patients with febrile ANP were enrolled and 30 patients (38.5%) were confirmed infected pancreatic necrosis (IPN). Compared with procalcitonin and blood culture, mNGS showed a significantly higher sensitivity rate (86.7% vs. 56.7% vs. 26.7%, P<0.001). Moreover, mNGS outperformed procalcitonin (89.5% vs. 61.4%, P<0.01) and blood culture (89.5% vs. 69.0%, P<0.01) in terms of negative predictive value. Blood mNGS exhibited the highest accuracy (85.7%) in diagnosing IPN and sterile pancreatic necrosis (SPN), significantly superior to both procalcitonin (65.7%) and blood culture (61.4%). In the multivariate analysis, positive blood mNGS (OR=60.2, P<0.001) and lower fibrinogen level (OR=2.0, P<0.05) were identified as independent predictors associated with IPN, whereas procalcitonin was not associated with IPN, but with increased mortality (OR=11.7, P=0.006). Overall, the rate of correct use of antibiotics in the cohort was only 18.6% (13/70) and would be improved to 81.4% (57/70) if adjusted according to the mNGS results. CONCLUSION: Blood mNGS represents important progress in the early diagnosis of IPN, with particular importance in guiding antibiotic usage for patients with febrile ANP.

4.
J Med Chem ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38375763

RESUMO

DNA polymerase theta (Polθ) has recently emerged as a new attractive synthetic lethal target involved in DNA damage repair. Inactivating Polθ alone or in combination with PARP inhibitors has demonstrated substantial therapeutic potential against tumors with homologous recombination (HR) defects such as alternation of BRCA genes. Herein, we report the design and proof of concept of a highly potent dual Polθ/PARP inhibitor 25d, which exhibited low nanomolar inhibitory activities against both Polθ and PARP1. Compared to combination treatment, 25d demonstrated superior antitumor efficacy in both MDA-MB-436 cells and xenografts by inducing more DNA damage and apoptosis. Importantly, 25d retained sensitivity in PARP inhibitor-resistant MDA-MB-436 cells with 53BP1 defect. Altogether, these findings illustrate the potential advantages of 25d, a first-in-class dual Polθ/PARP inhibitor, over monotherapy in treating HR-deficient tumors, including those with acquired PARP inhibitor resistance.

5.
Cancer Lett ; 587: 216702, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38336288

RESUMO

Resistance to trastuzumab and the poor efficacy of subsequent chemotherapy have become major challenges for HER2-positive gastric cancer (GC). As resistance evolves, tumor cells may acquire a new drug susceptibility profile, profoundly impacting the subsequent treatment selection and patient survival. However, the interplay between trastuzumab and other types of drugs in HER2-positive GC remains elusive. In our study, we utilized resistant cell lines and tissue specimens to map the drug susceptibility profile of trastuzumab-resistant GC, discovering that resistance to trastuzumab induces collateral resistance to commonly used chemotherapeutic agents. Additionally, patients with collateral resistance distinguished by a 13-gene scoring model in HER2-positive GC cohorts are predicted to have a poor prognosis and may be sensitive to cholesterol-lowering drugs. Mechanistically, endosomal cholesterol transport is further confirmed to enrich cholesterol in the plasma membrane, contributing to collateral resistance through the Hedgehog-ABCB1 axis. As a driver for cholesterol, Cdc42 is activated by the formation of the NPC1-TßRI-Cdc42 complex to facilitate endosomal cholesterol transport. We demonstrated that inhibiting Cdc42 activation with ZCL278 reduces cholesterol levels in the plasma membrane and reverses collateral resistance between trastuzumab and chemotherapy in vitro and in vivo. Collectively, our findings verify the phenomena and mechanism of collateral resistance between trastuzumab and chemotherapy, and propose a potential therapeutic target and strategy in the second-line treatment for trastuzumab-resistant HER2-positive GC.

6.
Mutat Res Rev Mutat Res ; 793: 108489, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38355091

RESUMO

Gastric cancer (GC) is the fifth most prevalent malignancy and the third leading cause of cancer-related mortality globally. Despite intensive efforts to enhance the efficiencies of various therapeutics (chemotherapy, surgical interventions, molecular-targeted therapies, immunotherapies), the prognosis for patients with GC remains poor. This might be predominantly due to the limited understanding of the complicated etiology of GC. Importantly, epigenetic modifications and alterations are crucial during GC development. Super-enhancers (SEs) are a large cluster of adjacent enhancers that greatly activate transcription. SEs sustain cell-specific identity by enhancing the transcription of specific oncogenes. In this review, we systematically summarize how SEs are involved in GC development, including the SE landscape in GC, the SE target genes in GC, and the interventions related to SE functions for treating GC.

7.
J Am Chem Soc ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38377334

RESUMO

Aqueous electrochemical coupling reactions, which enable the green synthesis of complex organic compounds, will be a crucial tool in synthetic chemistry. However, a lack of informed approaches for screening suitable catalysts is a major obstacle to its development. Here, we propose a pioneering electrochemical reductive coupling reaction toward direct electrosynthesis of oxime from NOx and aldehyde. Through integrating experimental and theoretical methods, we screen out the optimal catalyst, i.e., metal Fe catalyst, that facilitates the enrichment and C-N coupling of key reaction intermediates, all leading to high yields (e.g., ∼99% yield of benzaldoxime) for the direct electrosynthesis of oxime over Fe. With a divided flow reactor, we achieve a high benzaldoxime production of 22.8 g h-1 gcat-1 in ∼94% isolated yield. This work not only paves the way to the industrial mass production of oxime via electrosynthesis but also offers references for the catalyst selection of other electrochemical coupling reactions.

8.
Nutrition ; 121: 112365, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38377700

RESUMO

OBJECTIVES: The practicality and effectiveness of using the prognostic value of the neutrophil-to-albumin ratio (NAR) in evaluating patients with cancer remain unclear, and research is needed to fully understand its potential application in the cancer population. METHODS: The Kaplan-Meier method was used for survival analysis, and the log-rank test was employed for comparison. Univariate and multivariate Cox proportional hazards models were used to determine the prognostic biomarkers, and Logistic regression analysis was conducted to investigate the relationship between NAR and 90-day outcomes and cachexia. RESULTS: The study included 14 682 patients with cancer, divided into discovery (6592 patients), internal validation (2820 patients), and external validation groups (5270 patients). Patients with high NAR had higher all-cause mortality than those with low NAR in the discovery (50.15% versus 69.29%, P < 0.001), internal validation (54.18% versus 70.91%, P < 0.001), and external validation cohorts (40.60% versus 66.68%, P < 0.001). In the discovery cohort, high NAR was observed to be independently associated with all-cause mortality in patients (HR 1.16, 95% CI 1.12-1.19; P < 0.001). Moreover, we validated the promising prognostic value of NAR as a predictor of survival in patients with cancer through internal validation (HR 1.21, 95% CI 1.16-1.27, P < 0.001) and external validation cohorts (HR 1.27, 95% CI 1.21-1.34, P < 0.001). Additionally, in the subgroup analysis by tumor type, high NAR was identified as a risk factor for most cancers, except for breast cancer. CONCLUSIONS: This study showed that NAR is a feasible and promising biomarker for predicting prognosis and cancer cachexia in cancer patients.

9.
Angew Chem Int Ed Engl ; : e202400956, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38388935

RESUMO

We have accomplished the first and asymmetric total synthesis of principinol B, a grayanoids possessing an oxa-bicyclo[3.2.1] architecture. A functionalized 5/7/6/5 tetracyclic intermediate was assembled in a convergent manner by a diastereoselective intermolecular aldol reaction and a following carbonyl-olefin metathesis of two enantioenriched fragments. The oxa-bicyclo[3.2.1] architecture constituted of a 6,10-epoxide was constructed by a Williamson ether synthesis.

10.
Ther Adv Infect Dis ; 11: 20499361241231147, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38410828

RESUMO

Background: Considering the therapeutic difficulties and mortality associated with bloodstream infection (BSI), it is essential to investigate other potential factors affecting mortality in critically ill patients with BSI and examine the utility of the quick Pitt bacteremia (qPitt) score to improve the survival rate. Objectives: To improve the predictive accuracy of the qPitt scoring system by evaluating the five current components of qPitt and including other potential factors influencing mortality in critically ill patients with BSI. Design: This was a retrospective cohort study. Methods: Medical information from the Medical Information Mart for Intensive Care IV database was used in this retrospective cohort study. The risk factors associated with mortality were examined using a multivariate logistic regression model. The area under the receiver operating characteristic curve (AUC) was used to assess the discriminatory capability of the prediction models. Results: In total, 1240 eligible critically ill patients with BSI were included. After adjustment for age, community-onset BSI, indwelling invasive lines, and Glasgow Coma Scale (GCS) ⩽ 8, acute kidney injury (AKI) was identified as a notable risk factor for 14-day mortality. Except for altered mental status, the four other main components of the original qPitt were significantly associated with 14-day mortality. Hence, we established a modified qPitt (m-qPitt) by adding AKI and replacing altered mental status with GCS ⩽ 8. The AUCs for m-qPitt and qPitt were 0.723 [95% confidence interval (CI): 0.683-0.759] and 0.708 (95% CI: 0.669-0.745) in predicting 14-day mortality, respectively. Moreover, m-qPitt also had acceptable performance and discrimination power [0.700 (95% CI: 0.666-0.732)] in predicting 28-day mortality. Conclusion: AKI significantly influenced the survival of critically ill patients with BSIs. Compared with the original qPitt, our new m-qPitt was proven to have a better predictive performance for mortality in critically ill patients with BSI. Further studies should be conducted to validate the practicality of m-qPitt.

11.
Zhongguo Zhong Yao Za Zhi ; 49(2): 315-324, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38403307

RESUMO

Drying is an indispensable processing step for Chinese medicinal materials after harvesting. It often leads to significant changes in the active components of these materials, thus impacting their medicinal values. Understanding the mechanisms behind the changes during the drying process is of great importance for regulating the transformation of key active components. Therefore, this paper reviews the available studies and comprehensively expounds the mechanisms underlying the changes in active components during the drying process. The aim is to offer insights for the development of regulatory strategies and the improvement of drying techniques for Chinese medicinal materials.


Assuntos
Medicamentos de Ervas Chinesas , Dessecação
12.
J Inflamm (Lond) ; 21(1): 5, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38395896

RESUMO

BACKGROUND: Lactobacillus casei possesses many kinds of bioactivities, such as anti-inflammation and anti-oxidant, and has been applied to treating multiple inflammatory diseases. However, its role in mastitis prevention has remained ambiguous. METHODS: This study aimed to examine the mechanisms underlying the preventive effects of L. casei 03 against E. coli- mastitis utilizing bovine mammary epithelial cells (BMECs) and a mouse model. RESULTS: In vitro assays revealed pretreatment with L. casei 03 reduced the apoptotic ratio and the mRNA expression levels of IL1ß, IL6 and TNFα and suppressed phosphorylation of p65, IκBα, p38, JNK and ERK in the NF-κB signaling pathway and MAPK signaling pathway. Furthermore, in vivo tests indicated that intramammary infusion of L. casei 03 relieved pathological changes, reduced the secretion of IL1ß, IL6 and TNFα and MPO activity in the mouse mastitis model. CONCLUSIONS: These data suggest that L. casei 03 exerts protective effects against E. coli-induced mastitis in vitro and in vivo and may hold promise as a novel agent for the prevention and treatment of mastitis.

13.
Biomedicines ; 12(2)2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38397901

RESUMO

Liver disease-related mortality is a major cause of death worldwide. Hepatic innate and adaptive immune cells play diverse roles in liver homeostasis and disease. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells. MDSCs can be broadly divided into monocytic MDSCs and polymorphonuclear or granulocytic MDSCs, and they functionally interact with both liver parenchymal and nonparenchymal cells, such as hepatocytes and regulatory T cells, to impact liver disease progression. The infiltration and activation of MDSCs in liver disease can be regulated by inflammatory chemokines and cytokines, tumor-associated fibroblasts, epigenetic regulation factors, and gut microbiota during liver injury and cancer. Given the pivotal roles of MDSCs in advanced liver diseases, they can be targeted to treat primary and metastatic liver cancer, liver generation, alcoholic and nonalcoholic liver disease, and autoimmune hepatitis. Currently, several treatments such as the antioxidant and anti-inflammatory agent berberine are under preclinical and clinical investigation to evaluate their therapeutic efficacy on liver disease and their effect on MDSC infiltration and function. Phenotypic alteration of MDSCs in different liver diseases that are in a model-dependent manner and lack special markers for distinct MDSCs are challenges for targeting MDSCs to treat liver disease. Multi-omics study is an option to uncover the features of disease-specific MDSCs and potential gene or protein targets for liver disease treatment. In summary, MDSCs play important roles in the pathogenesis and progression of liver disease by regulating both intrahepatic innate and adaptive immune responses.

14.
N Engl J Med ; 390(8): 701-711, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38329148

RESUMO

BACKGROUND: Thrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.5 hours is limited. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving patients with ischemic stroke to compare tenecteplase (0.25 mg per kilogram of body weight, up to 25 mg) with placebo administered 4.5 to 24 hours after the time that the patient was last known to be well. Patients had to have evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging. The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death) at day 90. Safety outcomes included death and symptomatic intracranial hemorrhage. RESULTS: The trial enrolled 458 patients, 77.3% of whom subsequently underwent thrombectomy; 228 patients were assigned to receive tenecteplase, and 230 to receive placebo. The median time between the time the patient was last known to be well and randomization was approximately 12 hours in the tenecteplase group and approximately 13 hours in the placebo group. The median score on the modified Rankin scale at 90 days was 3 in each group. The adjusted common odds ratio for the distribution of scores on the modified Rankin scale at 90 days for tenecteplase as compared with placebo was 1.13 (95% confidence interval, 0.82 to 1.57; P = 0.45). In the safety population, mortality at 90 days was 19.7% in the tenecteplase group and 18.2% in the placebo group, and the incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively. CONCLUSIONS: Tenecteplase therapy that was initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery, most of whom had undergone endovascular thrombectomy, did not result in better clinical outcomes than those with placebo. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by Genentech; TIMELESS ClinicalTrials.gov number, NCT03785678.).


Assuntos
Isquemia Encefálica , AVC Isquêmico , Imagem de Perfusão , Tenecteplase , Trombectomia , Ativador de Plasminogênio Tecidual , Humanos , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/mortalidade , Isquemia Encefálica/cirurgia , Fibrinolíticos/administração & dosagem , Fibrinolíticos/efeitos adversos , Fibrinolíticos/uso terapêutico , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/diagnóstico por imagem , Perfusão , Imagem de Perfusão/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/cirurgia , Tenecteplase/administração & dosagem , Tenecteplase/efeitos adversos , Tenecteplase/uso terapêutico , Trombectomia/efeitos adversos , Trombectomia/métodos , Ativador de Plasminogênio Tecidual/administração & dosagem , Ativador de Plasminogênio Tecidual/efeitos adversos , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do Tratamento , Método Duplo-Cego , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/mortalidade , AVC Isquêmico/cirurgia , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/cirurgia , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/tratamento farmacológico , Doenças das Artérias Carótidas/cirurgia , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Tempo para o Tratamento
15.
ACS Appl Mater Interfaces ; 16(7): 9060-9067, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38336611

RESUMO

Filter-free wavelength-selective photodetectors have garnered significant attention due to the growing demand for smart sensors, artificial intelligence, the Internet of Everything, and so forth. However, the challenges associated with large-scale preparation and compatibility with complementary metal-oxide-semiconductor (CMOS) technology limit their wide-ranging applications. In this work, we address the challenges by constructing vertically stacked graded-band-gap zinc-tin oxide (ZTO) thin-film transistors (TFTs) specifically designed for wavelength-selective photodetection. The ZTO thin films with various band gaps are fabricated via atomic layer deposition (ALD) by varying the ALD cycle ratios of zinc oxide (ZnO) and SnO2. The ZTO film with a small Sn ratio exhibits a decreased band gap, and the resultant TFT shows a degraded performance, which can be attributed to the Sn4+ dopant introducing a series of deep-state energy levels in the ZnO band gap. As the ratio of Sn increases further, the band gap of the ZTO also increases, and the mobility of the ZTO TFT increases up to 30 cm2/V s, with a positive shift of the threshold voltage. The photodetectors employing ZTO thin films with distinct band gaps show different spectral responsivities. Then, vertically stacked ZTO (S-ZTO) thin films, with gradient band gaps increasing from the bottom to the top, have been successfully deposited using consecutive ALD technology. The S-ZTO TFT shows decent performance with a mobility of 18.4 cm2/V s, a threshold voltage of 0.5 V, an on-off current ratio higher than 107, and excellent stability under ambient conditions. The resultant S-ZTO TFT also exhibits obviously distinct photoresponses to light at different wavelength ranges. Furthermore, a device array of S-ZTO TFTs demonstrates color imaging by precisely reconstructing patterned illuminations with different wavelengths. Therefore, this work provides CMOS-compatible and structure-compact wavelength-selective photodetectors for advanced and integrable optoelectronic applications.

16.
J Ethnopharmacol ; 325: 117776, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38307354

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Honeysuckle, first documented in the Miscellaneous Records of Famous Physicians, is known for its ability to expel toxin and cool blood to stop diarrhea. Modern pharmacological research has shown that honeysuckle has anti-inflammatory, antibacterial, antioxidant, and immune-regulating effects and is widely used in clinical practice. However, the effect of honeysuckle on ulcerative colitis (UC) is still not fully understood, which presents challenges for quality control, research and development. AIM OF THE STUDY: This study aimed to determine the anti-inflammatory properties and mechanism of action of aqueous extracts of honeysuckle in the treatment of ulcerative colitis. MATERIALS AND METHODS: The dextran sodium sulfate (DSS) induced-ulcerative colitis mouse model was established, and the mice were divided into five groups: the control group, the model group, and the low, medium, and high dose honeysuckle treatment groups. RESULTS: All dose groups of honeysuckle were found to significantly reduce IL-6 and TNF-α levels and regulate DSS-induced mRNA levels of CLDN4, COX-2, IL-6, INOS, MUC-2, occludin and NLRP3. The high-dose group displayed the most effective inhibition, and a differentially expressed mRNA detection indicated abnormal mRNA expression. The 16sRNA sequencing revealed that the honeysuckle was able to significantly upregulate the abundance of beneficial bacteria and downregulate the abundance of harmful bacteria. The study of short-chain fatty acids revealed that the levels of acetic, propionic, isobutyric, valeric and isovaleric acids were significantly increased after administering honeysuckle at medium and high doses. CONCLUSION: Honeysuckle reduces the production of pro-inflammatory cytokines, increases the content of short-chain fatty acids and restores the intestinal ecological balance, resulting in better therapeutic effects.


Assuntos
Colite Ulcerativa , Colite , Lonicera , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colo , Interleucina-6/genética , Interleucina-6/metabolismo , Anti-Inflamatórios/efeitos adversos , RNA Mensageiro/metabolismo , Ácidos Graxos Voláteis/metabolismo , Sulfato de Dextrana/toxicidade , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Colite/tratamento farmacológico
17.
Heliyon ; 10(2): e24696, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38304815

RESUMO

Background: Sarcopenic obesity (SO) is a condition characterized by the coexistence of sarcopenia (loss of muscle mass and function) and obesity. This condition has emerged as a public health concern, particularly with the aging population. Despite an approximately 30-year history of SO research, detailed quantitative analysis of existing research was never undertaken. We aimed to depict the landscape of SO research using bibliometric analysis of literature. Methods: We searched the Web of Science Core Collection on January 15, 2023. The following bibliometric indicators were included: publication trend, the most influential country, the most active discipline, productive institutions, productive journals, prolific and highly cited authors, and highly cited publications. We constructed co-authorship network to explore individual-level, institutional-level, and international-level collaborative patterns in the VOSviewer or Sci2 software. Furthermore, keywords co-occurrence network was extracted by the VOSviewer software, and the burst-detection analysis of keywords was performed using the CiteSpace software. Results: A total of 2023 original articles were retrieved for data analysis. The publications increased dramatically in the last decade. The United States had the highest number of publications on SO (n = 904). The Seoul National University Hospital was the most prolific institution (n = 54) among the 2675 institutions analyzed. As for journals, Clinical Nutrition had the highest number of publications on SO (n = 75). Kim JH was the most prolific author (n = 25), while Cederholm T authored the most cited publication (9381 citations). More than 80 disciplines were involved in SO research, of which, "Geriatrics and Gerontology" was the most activated discipline. The European Working Group on Sarcopenia in Older People (EWGSOP) consensus was the most cited publication (7209 citations). Moreover, the hotspots of SO have been shifting from its biology, prevalence, and risk factors to its outcomes, prognostic factors, complications, and quality of life. Its relationships also evolved from being between SO and aging to being between SO and other diseases. Conclusions: Our study provided a comprehensive landscape of SO research, which may help researchers better identify key information and research trends in this field.

18.
Evol Appl ; 17(2): e13651, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38362509

RESUMO

The use of whole-genome sequence (WGS) data is expected to improve genomic prediction (GP) power of complex traits because it may contain mutations that in strong linkage disequilibrium pattern with causal mutations. However, a few previous studies have shown no or small improvement in prediction accuracy using WGS data. Incorporating prior biological information into GP seems to be an attractive strategy that might improve prediction accuracy. In this study, a total of 6334 pigs were genotyped using 50K chips and subsequently imputed to the WGS level. This cohort includes two prior discovery populations that comprise 294 Landrace pigs and 186 Duroc pigs, as well as two validation populations that consist of 3770 American Duroc pigs and 2084 Canadian Duroc pigs. Then we used annotation information and genome-wide association study (GWAS) from the WGS data to make GP for six growth traits in two Duroc pig populations. Based on variant annotation, we partitioned different genomic classes, such as intron, intergenic, and untranslated regions, for imputed WGS data. Based on GWAS results of WGS data, we obtained trait-associated single-nucleotide polymorphisms (SNPs). We then applied the genomic feature best linear unbiased prediction (GFBLUP) and genomic best linear unbiased prediction (GBLUP) models to estimate the genomic estimated breeding values for growth traits with these different variant panels, including six genomic classes and trait-associated SNPs. Compared with 50K chip data, GBLUP with imputed WGS data had no increase in prediction accuracy. Using only annotations resulted in no increase in prediction accuracy compared to GBLUP with 50K, but adding annotation information into the GFBLUP model with imputed WGS data could improve the prediction accuracy with increases of 0.00%-2.82%. In conclusion, a GFBLUP model that incorporated prior biological information might increase the advantage of using imputed WGS data for GP.

19.
BMC Med Imaging ; 24(1): 40, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347469

RESUMO

PURPOSE: Both of extracellular extravascular volume (EEV) and extracellular volume fraction (ECV) were proposed to quantify enlargement of myocardial interstitial space due to myocardium loss or fibrosis. The study aimed to investigate the feasibility of using EEV derived from myocardial computed tomography (CT) perfusion imaging (VPCT) and extracellular volume quantification with single-energy subtraction CT (ECV- SECT) for quantifying myocardial fibrosis. METHODS: In this study, 17 patients with suspected and known coronary artery disease underwent examination using a dual-source CT scanner. The EEV- VPCT was derived from dynamic whole-heart myocardial perfusion imaging, and the ECV_SECT was calculated from late-enhanced images 5 min after bolus contrast injection by subtracting the noncontrast baseline. The late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging was used as a reference. RESULTS: In total, 11 patients and 73 segments exhibited positivity for LGE on CMR imaging. These were classified into three groups according to the segments: fibrotic segments (group I, n = 73), nonfibrotic segments in LGE-positive patients (group II, n = 103), and segments in LGE-negative patients (group III, n = 80). ECV- SECT, EEV- VPCT, myocardial blood flow (MBF), and myocardial blood volume (MBV) significantly differed among these groups (all P < 0.05). ECV- SECT was significantly higher and EEV- VPCT, MBF, and MBV were significantly lower in fibrotic myocardial segments than in nonfibrotic ones (all P < 0.01). ECV- SECT and EEV- VPCT independently affected myocardial fibrosis. There was no significant correlation between ECV- SECT and EEV- VPCT. The capability of EEV- VPCT to diagnose myocardial fibrosis was equivalent to that of ECV- SECT (area under the curve: 0.798 vs. 0.806, P = 0.844). ECV- SECT of > 41.2% and EEV- VPCT of < 10.3% indicated myocardial fibrosis. CONCLUSIONS: EEV- VPCT is actually first-pass distribution volume that can feasibly be used to quantify myocardial fibrosis. Furthermore, the diagnostic efficacy of EEV- VPCT is comparable to that of ECV- SECT.


Assuntos
Cardiomiopatias , Imagem de Perfusão do Miocárdio , Humanos , Meios de Contraste , Imagem de Perfusão do Miocárdio/métodos , Gadolínio , Miocárdio/patologia , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Fibrose , Valor Preditivo dos Testes , Imagem Cinética por Ressonância Magnética/métodos
20.
Cancer Control ; 31: 10732748241230888, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38303637

RESUMO

OBJECTIVES: To explore the effect of combined hematological and physical measurement indicators on the prognosis of patients undergoing surgery for gastric or colorectal cancer and to screen for the best prognostic indicators. INTRODUCTION: Gastric and colorectal cancer is a widespread health concern worldwide and one of the major contributors to cancer-related death. The hematological and physical measurement indicators have been shown to associate with the prognosis of patients undergoing surgery for gastric or colorectal cancer, respectively, but it is still unclear whether the combination of the two can reflect the prognosis more effectively. METHODS: Thirteen hematological indicators and 5 physical measurement indicators were selected in this study, and the most promising ones were screened using LASSO regression. Then, the best prognostic indicators were selected by time-ROC curves. Survival curves were constructed using the Kaplan-Meier method, and the effects of hematological and physical measurement indicators on the prognosis of patients undergoing surgery for gastric or colorectal cancers were evaluated by Cox proportional risk regression analysis. In addition, the relationship between hematological and physical measurement indicators on secondary outcomes, including length of stay, hospitalization costs, intensive care unit (ICU) admission, and patients' subjective global assessment scores (PGSGA), was explored. RESULTS: After initial screening, among the hematological indicators, the geriatric nutritional risk index (GNRI) showed the highest mean area under the curve (AUC) values. Among body measures, calf circumference (CC) showed the highest mean AUC value. Further analyses showed that the combination of combined nutritional prognostic index (GNRI) and calf circumference (CC) (GNRI-CC) had the best performance in predicting the prognosis of patients undergoing surgery for gastric or colorectal cancers. Low GNRI, low CC, and low GNRI-low CC increased the risk of death by 44%, 48%, and 104%, respectively. Sensitivity analyses showed the same trend. In addition, low GNRI-low CC increased the risk of malnutrition by 17%. CONCLUSION: This study emphasizes that a combination of blood measures and body measures is essential to accurately assess the prognosis of patients undergoing surgery for gastric or colorectal cancers. The GNRI-CC is a good prognostic indicator and can also assess the risk of possible malnutrition.


Assuntos
Neoplasias Colorretais , Desnutrição , Humanos , Idoso , Estado Nutricional , Prognóstico , Desnutrição/diagnóstico , Avaliação Nutricional , Neoplasias Colorretais/cirurgia , Avaliação Geriátrica/métodos , Estudos Retrospectivos , Fatores de Risco
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