Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.008
Filtrar
1.
BMJ Open ; 14(7): e083460, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38969370

RESUMO

INTRODUCTION: Postoperative ileus (POI) is a postoperative complication that can cause lingering recovery after colorectal resection and a heavy healthcare system burden. Acupuncture aims to prevent postoperative complications, reduce the duration of POI, help recovery and shorten hospital stays. We hypothesise that preoperative electroacupuncture (EA) can promote POI recovery under the enhanced recovery after surgery protocol after laparoscopic surgery in patients with POI. METHODS AND ANALYSIS: This is a multicentre, randomised, sham-controlled trial. A total of 80 patients will be enrolled and randomly assigned to the EA or sham electroacupuncture (SA) group. The eligible patients will receive EA or SA for one session per day with treatment frequency starting on preoperative day 1 for four consecutive days. The primary outcome is the time to first defecation. The secondary outcomes include the time to first flatus, length of postoperative hospital stay, time to tolerability of semiliquid and solid food, postoperative nausea, vomiting, pain and extent of abdominal distention, time to first ambulation, preoperative anxiety, 30-day readmission rate, the usage of anaesthetics and analgesics during operation, length of postanaesthesia care unit stay. A mechanistic study by single-cell RNA sequencing in which postintervention normal intestinal tissue samples will be collected. The results of this study will provide evidence of the effects of acupuncture on POI and promote good clinical decision to millions of patients globally every year. ETHICS AND DISSEMINATION: This study has been approved by the ethical application of Beijing University of Chinese Medicine (2022BZYLL0401), Beijing Friendship Hospital Affiliated to Capital Medical University(2022-P2-368-02), Cancer Hospital Chinese Academy of Medical Science (23/175-3917), Huanxing Cancer Hospital (2023-002-02). The results will be published in a medical journal. In addition, we plan to present them at scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300077633.


Assuntos
Neoplasias Colorretais , Eletroacupuntura , Íleus , Laparoscopia , Complicações Pós-Operatórias , Humanos , Eletroacupuntura/métodos , Laparoscopia/efeitos adversos , Íleus/etiologia , Íleus/terapia , Neoplasias Colorretais/cirurgia , Complicações Pós-Operatórias/terapia , Complicações Pós-Operatórias/etiologia , China , Tempo de Internação/estatística & dados numéricos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Cuidados Pré-Operatórios/métodos , Feminino , Adulto , Masculino
2.
J Nanobiotechnology ; 22(1): 391, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965509

RESUMO

BACKGROUND: Prostate cancer (PCa) has a high incidence in men worldwide, and almost all PCa patients progress to the androgen-independent stage which lacks effective treatment measures. PTENP1, a long non-coding RNA, has been shown to suppress tumor growth through the rescuing of PTEN expression via a competitive endogenous RNA (ceRNA) mechanism. However, PTENP1 was limited to be applied in the treatment of PCa for the reason of rapid enzymatic degradation, poor intracellular uptake, and excessively long base sequence to be synthesized. Considering the unique advantages of artificial nanomaterials in drug loading and transport, black phosphorus (BP) nanosheet was employed as a gene-drug carrier in this study. RESULTS: The sequence of PTENP1 was adopted as a template which was randomly divided into four segments with a length of about 1000 nucleotide bases to synthesize four different RNA fragments as gene drugs, and loaded onto polyethyleneimine (PEI)-modified BP nanosheets to construct BP-PEI@RNA delivery platforms. The RNAs could be effectively delivered into PC3 cells by BP-PEI nanosheets and elevating PTEN expression by competitive binding microRNAs (miRNAs) which target PTEN mRNA, ultimately exerting anti-tumor effects. CONCLUSIONS: Therefore, this study demonstrated that BP-PEI@RNAs is a promising gene therapeutic platform for PCa treatment.


Assuntos
Nanoestruturas , PTEN Fosfo-Hidrolase , Fósforo , Neoplasias da Próstata , Masculino , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Humanos , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Fósforo/química , Nanoestruturas/química , MicroRNAs/genética , Linhagem Celular Tumoral , Células PC-3 , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Polietilenoimina/química , Animais , Técnicas de Transferência de Genes , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , RNA Endógeno Competitivo
3.
Heliyon ; 10(12): e32391, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38975114

RESUMO

Background: Postoperative hypothermia (POH) is a common issue in colorectal surgery patients, leading to complications. This study aimed to develop and validate a predictive model for identifying POH in colorectal surgery patients. Methods: A retrospective analysis of 1,316 patients who underwent colorectal surgery between June 2020 and September 2022 was conducted using institutional medical records. Intraoperative core temperatures and potential influencing factors were collected, and regression analysis was used to identify risk factors for POH and create a model. The model's performance was evaluated using the receiver operating characteristic curve analysis. Results: Intraoperative hypothermia occurred in 51.5 % of patients. Significant predictors of POH included gender, alcohol consumption, surgery duration, platelet count, and age. The constructed model included factors like fluid intake, platelets, cigarette use, alcohol consumption, surgery type, muscle relaxants, age, ABSI, and gender. The model showed good predictive performance with an area under the ROC curve of 0.981 and a Hosmer-Lemeshow test p-value of 0.676. The Youden index, sensitivity, specificity, and practical application rate were 0.602, 0.790, 0.812, and 98.81 %, respectively. Conclusion: This study developed a predictive model for POH in colorectal surgery patients, considering individual factors and exploring underlying causes. Understanding risk factors and consequences of POH is crucial for nurses and perioperative professionals in clinical practice.

4.
Mar Drugs ; 22(6)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38921548

RESUMO

Six new compounds, talamitones A and B (1 and 2), demethyltalamitone B (3), talamiisocoumaringlycosides A and B (4 and 5), and talaminaphtholglycoside (6), together with six known compounds (7-12), were isolated from the marine-derived fungus Talaromyces minnesotensis BTBU20220184. The new structures were characterized by using HRESIMS and NMR. This is the first report of isocoumaringlycoside derivatives from a fungus of the Talaromyces genus. Compounds 5, 6, and 9 showed synergistic antibacterial activity against Staphylococcus aureus.


Assuntos
Antibacterianos , Staphylococcus aureus , Talaromyces , Talaromyces/química , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Organismos Aquáticos , Testes de Sensibilidade Microbiana , Metabolismo Secundário , Estrutura Molecular , Espectroscopia de Ressonância Magnética
5.
Mar Drugs ; 22(6)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38921570

RESUMO

A new dimeric C-glycoside polyketide chrysomycin F (1), along with four new monomeric compounds, chrysomycins G (2), H (3), I (4), J (5), as well as three known analogues, chrysomycins A (6), B (7), and C (8), were isolated and characterised from a strain of Streptomyces sp. obtained from a sediment sample collected from the South China Sea. Their structures were determined by detailed spectroscopic analysis. Chrysomycin F contains two diastereomers, whose structures were further elucidated by a biomimetic [2 + 2] photodimerisation of chrysomycin A. Chrysomycins B and C showed potent anti-tuberculosis activity against both wild-type Mycobacterium tuberculosis and a number of clinically isolated MDR M. tuberculosis strains.


Assuntos
Antituberculosos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis , Policetídeos , Streptomyces , Streptomyces/química , Streptomyces/metabolismo , Mycobacterium tuberculosis/efeitos dos fármacos , Antituberculosos/farmacologia , Antituberculosos/química , Antituberculosos/isolamento & purificação , Policetídeos/farmacologia , Policetídeos/química , Policetídeos/isolamento & purificação , Glicosídeos/química , Glicosídeos/farmacologia , Glicosídeos/isolamento & purificação , China , Estrutura Molecular , Antraquinonas/farmacologia , Antraquinonas/química , Antraquinonas/isolamento & purificação
6.
J Neurointerv Surg ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914462

RESUMO

BACKGROUND: Endovascular treatment for vertebral artery dissecting aneurysms (VADAs) includes overlapping stents and flow diverters. This study compared the safety and effectiveness of overlapping stents and flow diverters for unruptured VADAs. METHODS: We retrospectively enrolled patients with unruptured VADAs who underwent overlapping stents or flow diverters at two tertiary hospitals in South Korea. The primary clinical outcome was the occurrence of stroke. The primary angiographic outcomes (>12 months) were categorized as regression, no decrease in size, recanalization, or stent occlusion, of which only regression was defined as a favorable angiographic outcomes. RESULTS: Of the 146 patients with VADAs, 25 (17.1%) had flow diverters and 121 (82.9%) had overlapping stents. For the primary angiographic outcomes over 12 months, the rate of favorable angiographic outcomes for flow diverters was 81.8% and for overlapping stents (triple stents) was 98.8% (P=0.006). In the multivariale analysis, after adjusting for partially thrombosed aneurysms, aneurysm shape, non-dominant vessel, posterior inferior cerebellar artery involvement, and procedure type, overlapping stents (triple stents) was not associated with favorable angiographic outcomes compared with flow diverters (OR 7.040, 95% CI 0.549 to 90.294; P=0.134), but partially thrombosed aneurysms was inversely associated with favorable angiographic outcomes (OR 0.056, 95% CI 0.005 to 0.589; P=0.016). The primary clinical outcome followed up to the last angiography did not occur in all patients. CONCLUSION: There was no difference in safety and effectiveness between overlapping stents and flow diverters in unruptured VADAs. Further endovascular treatment studies are needed regarding the association of partially thrombosed aneurysms with unfavorable angiographic outcomes.

7.
ACS Appl Mater Interfaces ; 16(26): 33404-33415, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38904481

RESUMO

Triboelectric nanogenerators (TENGs) have garnered substantial attention in breeze wind energy harvesting. However, how to improve the output performance and reduce friction and wear remain challenging. To this end, a blade-type triboelectric-electromagnetic hybrid generator (BT-TEHG) with a double frequency up-conversion (DFUC) mechanism is proposed. The DFUC mechanism enables the TENG to output a high-frequency response that is 15.9 to 300 times higher than the excitation frequency of 10 to 200 rpm. Coupled with the collisions between tribomaterials, a higher surface charge density and better generating performance are achieved. The magnetization direction and dimensional parameters of the BT-TEHG were optimized, and its generating characteristics under varying rotational speeds and electrical boundary conditions were studied. At wind speeds of 2.2 and 10 m/s, the BT-TEHG can generate, respectively, power of 1.30 and 19.01 mW. Further experimentation demonstrates its capacity to charge capacitors, light up light emitting diodes (LEDs), and power wireless temperature and humidity sensors. The demonstrations show that the BT-TEHG has great potential applications in self-powered wireless sensor networks (WSNs) for environmental monitoring of intelligent agriculture.

8.
Phytomedicine ; 132: 155808, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38876007

RESUMO

BACKGROUND: C. deserticola, a highly esteemed medicinal herb in China, commonly referred to as "desert ginseng", has been renowned for its unique pharmacological properties in clinical use for countless centuries. Despite its long-standing reputation, our current comprehension of its active components and pharmacological effects remains shallow and incomplete. Moreover, the unclear mechanism underlying its pharmacological actions hinders the advancement and utilization of novel drug formulations derived from C. deserticola. Furthermore, as a unique parasitic plant, the current research on its parasitic mechanisms is limited, hampering efforts to enhance both its medicinal composition and overall yields. PURPOSE: The objective of this review is to meticulously assess, condense, and evaluate the salient aspects pertaining to the chemical composition, pharmacological impacts, and parasitic mechanisms of C. deserticola. Furthermore, the aim is to furnish valuable references that can inform and guide future research endeavors and developmental activities related to C. deserticola. METHODS: This review adheres to the rigorous standards outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A thorough examination and analysis of pertinent research findings, published up to February 6, 2024, has been conducted. Databases such as PubMed, Scopus, Web of Science, Cochrane, and Science Direct were exhaustively searched using targeted keywords and operators to delve into the chemical constituents, pharmacological effects, and parasitic mechanisms exhibited by C. deserticola. RESULTS: The review comprehensively summarizes the advancements in research regarding the chemical composition, pharmacological impacts, and toxicological safety of C. deserticola. It delves into the parasitic mechanisms of C. deserticola from three distinct angles: seed germination, haustorium induction, and recognition of signal substances. Furthermore, the review pinpoints pertinent issues and offers insightful recommendations for future exploration and research pertaining to C. deserticola. CONCLUSION: In recent years, C. deserticola has garnered considerable attention due to its distinctive pharmacological properties. This comprehensive review aims to establish a scientific foundation for the development of potential novel drugs and the enhancement of both the quantity and quality of C. deserticola. It accomplishes this by meticulously analyzing and evaluating the latest research findings pertaining to its chemical composition, pharmacological impacts, and parasitic mechanisms.

9.
Drug Des Devel Ther ; 18: 1833-1853, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828018

RESUMO

Purpose: Given the potent immunostimulatory effects of bacterial outer membrane vesicles (OMVs) and the significant anti-colon tumor properties of Parabacteroides distasonis (Pd), this study aimed to elucidate the role and potential mechanisms of Pd-derived OMVs (Pd-OMVs) against colon cancer. Methods: This study isolated and purified Pd-OMVs from Pd cultures and assessed their characteristics. The effects of Pd-OMVs on CT26 cell uptake, proliferation, and invasion were investigated in vitro. In vivo, a CT26 colon tumor model was used to investigate the anti-colon tumor effects and underlying mechanisms of Pd-OMVs. Finally, we evaluated the biosafety of Pd-OMVs. Results: Purified Pd-OMVs had a uniform cup-shaped structure with an average size of 165.5 nm and a zeta potential of approximately -9.56 mV, and their proteins were associated with pathways related to immunity and apoptosis. In vitro experiments demonstrated that CT26 cells internalized the Pd-OMVs, resulting in a significant decrease in their proliferation and invasion abilities. Further in vivo studies confirmed the accumulation of Pd-OMVs in tumor tissues, which significantly inhibited the growth of colon tumors. Mechanistically, Pd-OMVs increased the expression of CXCL10, promoting infiltration of CD8+ T cells into tumor tissues and expression of pro-inflammatory factors TNF-α, IL-1ß, and IL-6. Notably, Pd-OMVs demonstrated a high level of biosafety. Conclusion: This paper elucidates that Pd-OMVs can exert significant anti-colon tumor effects by upregulating the expression of the chemokine CXCL10, thereby increasing the infiltration of CD8+ T cells into tumors and enhancing antitumor immune responses. This suggests that Pd-OMVs may be developed as a novel nanoscale potent immunostimulant with great potential for application in tumor immunotherapy. As well as developed as a novel nano-delivery carrier for combination with other antitumor drugs.


Assuntos
Linfócitos T CD8-Positivos , Proliferação de Células , Quimiocina CXCL10 , Neoplasias do Colo , Camundongos Endogâmicos BALB C , Neoplasias do Colo/imunologia , Neoplasias do Colo/patologia , Neoplasias do Colo/tratamento farmacológico , Animais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Camundongos , Proliferação de Células/efeitos dos fármacos , Quimiocina CXCL10/metabolismo , Quimiocina CXCL10/imunologia , Membrana Externa Bacteriana/imunologia , Membrana Externa Bacteriana/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Humanos , Neoplasias Experimentais/patologia , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/tratamento farmacológico , Ensaios de Seleção de Medicamentos Antitumorais , Células Tumorais Cultivadas
10.
Exp Brain Res ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842755

RESUMO

Vascular dementia (VaD) is the most common cause of dementia in older adults. Due to the lack of effective treatment options, there is an urgent need to find an effective pharmaceutical compound to combat VaD. Piracetam has been reported to improve impaired cognitive function in a variety of conditions in both human and animal models. However, the role and mechanism of Piracetam in VaD remain unclear. Therefore this study aimed to elucidate the effect of Piracetam on a cellular model of VaD in vitro. We found that Piracetam enhanced the growth of OGD-stimulated SH-SY5Y cells. In addition, Piracetam inhibited the oxidative stress of OGD-stimulated SH-SY5Y cells. Further, Piracetam improved mitochondrial function of OGD-stimulated SH-SY5Y cells. Mechanistically, Piracetam inhibited the PI3K/Akt/mTOR pathway in OGD-stimulated SH-SY5Y cells. Collectively, Piracetam improved oxidative stress and mitochondrial dysfunction of OGD-stimulated SH-SY5Y cells through PI3K/Akt/mTOR axis. Hence, Piracetam has the potential to serve as a promising drug of VaD.

11.
Biomicrofluidics ; 18(3): 031505, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38855476

RESUMO

Rapid identification of pathogens with higher sensitivity and specificity plays a significant role in maintaining public health, environmental monitoring, controlling food quality, and clinical diagnostics. Different methods have been widely used in food testing laboratories, quality control departments in food companies, hospitals, and clinical settings to identify pathogens. Some limitations in current pathogens detection methods are time-consuming, expensive, and laborious sample preparation, making it unsuitable for rapid detection. Microfluidics has emerged as a promising technology for biosensing applications due to its ability to precisely manipulate small volumes of fluids. Microfluidics platforms combined with spectroscopic techniques are capable of developing miniaturized devices that can detect and quantify pathogenic samples. The review focuses on the advancements in microfluidic devices integrated with spectroscopic methods for detecting bacterial microbes over the past five years. The review is based on several spectroscopic techniques, including fluorescence detection, surface-enhanced Raman scattering, and dynamic light scattering methods coupled with microfluidic platforms. The key detection principles of different approaches were discussed and summarized. Finally, the future possible directions and challenges in microfluidic-based spectroscopy for isolating and detecting pathogens using the latest innovations were also discussed.

12.
BMC Ophthalmol ; 24(1): 237, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844903

RESUMO

BACKGROUND: The purpose of this study was to investigate the photoprotection effect of peroxiredoxin 1 (PRDX1) protein in ultraviolet B (UVB) irradiation-induced damage of retinal pigment epithelium (RPE) and its possible molecular mechanism. METHODS: ARPE-19 cell viability and apoptosis were assessed by MTT assay and flow cytometry, respectively. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the PRDX1 expression. The corresponding kits were employed to measure the levels or activities of lactate dehydrogenase (LDH), 8-hydroxy-2-deoxyguanosine (8-OHdG), reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD). Western blotting was applied to examine PRDX1 expression and mitogen-activated protein kinase (MAPK) signaling pathway-related proteins. RESULTS: After exposure to 20 mJ/cm2 intensity of UVB irradiation for 24 h, ARPE-19 cells viability was decreased, the leakage degree of LDH and 8-OHdG were increased, and cell apoptosis was elevated. The expression of PRDX1 was significantly down-regulated in UVB-induced ARPE-19 cells. The low expression of PRDX1 was involved in high irradiation intensity. Overexpression of PRDX1 increased cell activity, decreased cell apoptosis, and LDH as well as 8-OHdG leakage in UVB-induced ARPE-19 cells. In addition to alleviating UVB-induced cell damage, PRDX1 overexpression also inhibited UVB-induced oxidative stress (down-regulation of ROS and MDA levels, up-regulation of GSH-Px and SOD activities) and the activation of MAPK signaling pathway in ARPE-19 cells. CONCLUSION: PRDX1 exerts a photoprotection effect on RPE by attenuating UVB-induced cell damage and inhibiting oxidative stress, which can be attributed to the inhibition of MAPK signaling pathway activation.


Assuntos
Apoptose , Sobrevivência Celular , Estresse Oxidativo , Peroxirredoxinas , Espécies Reativas de Oxigênio , Epitélio Pigmentado da Retina , Raios Ultravioleta , Humanos , Epitélio Pigmentado da Retina/efeitos da radiação , Epitélio Pigmentado da Retina/metabolismo , Peroxirredoxinas/metabolismo , Raios Ultravioleta/efeitos adversos , Espécies Reativas de Oxigênio/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Linhagem Celular , Western Blotting , Células Cultivadas , 8-Hidroxi-2'-Desoxiguanosina/metabolismo , Transdução de Sinais
13.
Colloids Surf B Biointerfaces ; 241: 114018, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38865868

RESUMO

The pressing need for highly efficient antibacterial strategies arises from the prevalence of microbial biofilm infections and the emergence of rapidly evolving antibiotic-resistant strains of pathogenic bacteria. Photodynamic therapy represents a highly efficient and compelling antibacterial approach, offering promising prospects for effective control of the development of bacterial resistance. However, the effectiveness of many photosensitizers is limited due to the reduced generation of reactive oxygen species (ROS) in hypoxic microenvironment, which commonly occur in pathological conditions such as inflammatory and bacteria-infected wounds. Herein, we designed and prepared two phenothiazine-derived photosensitizers (NB-1 and NB-2), which can effectively generate superoxide anion radicals (O2●-) through the type I process. Both photosensitizers demonstrate significant efficacy in vitro for the eradication of broad-spectrum bacteria. Moreover, NB-2 possesses distinct advantages including strong membrane binding and strong generation of O2●-, rendering it an exceptionally efficient antibacterial agent against mature biofilms. In addition, laser activated NB-2 could be applied to treat MRSA-infected wound in vivo, which offers new opportunities for potential practical applications.

14.
J Affect Disord ; 360: 229-241, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38823591

RESUMO

A high-fat diet can modify the composition of gut microbiota, resulting in dysbiosis. Changes in gut microbiota composition can lead to increased permeability of the gut barrier, allowing bacterial products like lipopolysaccharides (LPS) to enter circulation. This process can initiate systemic inflammation and contribute to neuroinflammation. Empagliflozin (EF), an SGLT2 inhibitor-type hypoglycemic drug, has been reported to treat neuroinflammation. However, there is a lack of evidence showing that EF regulates the gut microbiota axis to control neuroinflammation in HFD models. In this study, we explored whether EF could improve neuroinflammation caused by an HFD via regulation of the gut microbiota and the mechanism underlying this phenomenon. Our data revealed that EF alleviates pathological brain injury, reduces the reactive proliferation of astrocytes, and increases the expression of synaptophysin. In addition, the levels of inflammatory factors in hippocampal tissue were significantly decreased after EF intervention. Subsequently, the results of 16S rRNA gene sequencing showed that EF could change the microbial community structure of mice, indicating that the abundance of Lactococcus, Ligilactobacillus and other microbial populations decreased dramatically. Therefore, EF alleviates neuroinflammation by inhibiting gut microbiota-mediated astrocyte activation in the brains of high-fat diet-fed mice. Our study focused on the gut-brain axis, and broader research on neuroinflammation can provide a more holistic understanding of the mechanisms driving neurodegenerative diseases and inform the development of effective strategies to mitigate their impact on brain health. The results provide strong evidence supporting the larger clinical application of EF.


Assuntos
Astrócitos , Compostos Benzidrílicos , Dieta Hiperlipídica , Microbioma Gastrointestinal , Glucosídeos , Doenças Neuroinflamatórias , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Astrócitos/efeitos dos fármacos , Glucosídeos/farmacologia , Camundongos , Compostos Benzidrílicos/farmacologia , Doenças Neuroinflamatórias/tratamento farmacológico , Masculino , Camundongos Endogâmicos C57BL , Encéfalo/efeitos dos fármacos , Eixo Encéfalo-Intestino/efeitos dos fármacos , Modelos Animais de Doenças , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Disbiose
15.
Aging Clin Exp Res ; 36(1): 131, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38869742

RESUMO

BACKGROUND: Leukocyte telomere length (LTL) shorting was significantly associated with mortality. This study aimed to investigate the potential association between LTL and all-cause mortality as well as cardiovascular disease (CVD) mortality in middle-aged or older individuals without a history of CVD. METHODS: A total of 4174 participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2002 were included in this analysis. Cox proportional hazards regression models were utilized to estimate the association between LTL and mortality outcomes. Restricted cubic spline (RCS) curves were employed to evaluate the potential non-linear association. RESULTS: Over a median follow-up period of 217 months, the weighted rates of all-cause mortality and CVD mortality were 28.58% and 8.32% respectively. Participants in the highest LTL group exhibited a significantly decreased risk of both all-cause mortality (HR: 0.65, 95% CI: 0.54-0.78, P < 0.001) and CVD mortality (HR: 0.64, 95% CI: 0.45-0.93, P < 0.001) compared to those in the lowest group. Kaplan-Meier survival curves further supported a significant association between shorter telomere length and increased risks of both all-cause and CVD mortality (log-rank test P < 0.001). RCS curves demonstrated a linear dose-response relationship between LTL and all-cause mortality as well as CVD mortality. Subgroup and sensitivity analyses confirmed the robustness of the results. CONCLUSION: Shorter leukocyte telomere length could serve as a potential biomarker for risk stratification of all-cause and CVD mortality among middle-aged and older individuals without a history of CVD.


Assuntos
Doenças Cardiovasculares , Leucócitos , Inquéritos Nutricionais , Telômero , Humanos , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/genética , Masculino , Pessoa de Meia-Idade , Leucócitos/metabolismo , Feminino , Estudos Prospectivos , Telômero/genética , Idoso , Fatores de Risco
16.
Eur J Med Chem ; 274: 116546, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38823266

RESUMO

Cyclodextrin-based metal-organic frameworks (CD-MOFs) are gaining traction in the realm of drug delivery due to their inherent versatility and potential to amplify drug efficacy, specificity, and safety. This article explores the predominant preparation techniques for CD-MOFs, encompassing methods like vapor diffusion, microwave-assisted, and ultrasound hydrothermal approaches. Native CD-MOFs present compelling advantages in drug delivery applications. They can enhance drug loading capacity, stability, solubility, and bioavailability by engaging in diverse interactions with drugs, including host-guest, hydrogen bonding, and electrostatic interactions. Beyond their inherent properties, CD-MOFs can be customized as drug carriers through two primary strategies: co-crystallization with functional components and surface post-modifications. These tailored modifications pave the way for controlled release manners. They allow for slow and sustained drug release, as well as responsive releases triggered by various factors such as pH levels, glutathione concentrations, or specific cations. Furthermore, CD-MOFs facilitate targeted delivery strategies, like pulmonary or laryngeal delivery, enhancing drug delivery precision. Overall, the adaptability and modifiability of CD-MOFs underscore their potential as a versatile platform for drug delivery, presenting tailored solutions that cater to diverse biomedical and industrial needs.


Assuntos
Ciclodextrinas , Portadores de Fármacos , Estruturas Metalorgânicas , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/síntese química , Ciclodextrinas/química , Humanos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Animais
17.
Artigo em Inglês | MEDLINE | ID: mdl-38895981

RESUMO

Retinol saturase (RetSat) is an oxidoreductase involved in lipid metabolism and the cellular sensitivity to peroxides. RetSat is highly expressed in metabolic organs like liver and adipose tissue and its global loss in mice increases body weight and adiposity. The regulation of RetSat expression and its function in the intestine are unexplored. Here, we show that RetSat is present in different segments of the digestive system, localizes to intestinal epithelial cells, and is upregulated by feeding mice high-fat diet (HFD). Intestine-specific RetSat deletion in adult mice did not affect nutrient absorption and energy homeostasis basally, but lowered body weight gain and fat mass of HFD-fed mice, potentially via increasing locomotor activity. Moreover, jejunal expression of genes related to ß-oxidation and cholesterol efflux were decreased and colonic cholesterol content reduced upon RetSat deletion. In colitis, which we show to downregulate intestinal RetSat expression in humans and mice, RetSat ablation improved epithelial architecture of the murine colon. Thus, intestinal RetSat expression is regulated by dietary interventions and inflammation, and its loss reduces weight gain upon HFD-feeding and alleviates epithelial damage upon injury.

18.
Cell ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38936359

RESUMO

Duplication is a foundation of molecular evolution and a driver of genomic and complex diseases. Here, we develop a genome editing tool named Amplification Editing (AE) that enables programmable DNA duplication with precision at chromosomal scale. AE can duplicate human genomes ranging from 20 bp to 100 Mb, a size comparable to human chromosomes. AE exhibits activity across various cell types, encompassing diploid, haploid, and primary cells. AE exhibited up to 73.0% efficiency for 1 Mb and 3.4% for 100 Mb duplications, respectively. Whole-genome sequencing and deep sequencing of the junctions of edited sequences confirm the precision of duplication. AE can create chromosomal microduplications within disease-relevant regions in embryonic stem cells, indicating its potential for generating cellular and animal models. AE is a precise and efficient tool for chromosomal engineering and DNA duplication, broadening the landscape of precision genome editing from an individual genetic locus to the chromosomal scale.

19.
J Chromatogr A ; 1728: 465014, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-38797135

RESUMO

Developing novel chiral stationary phases (CSPs) with versatility is of great importance in enantiomer separation. This study fabricated a dual-chiral covalent organic framework (PA-CA COF) via successive post-synthetic modifications. The chiral trans-1,2-cyclohexanediamine (CA) and (D)-penicillamine (PA) groups were periodically aligned within nanochannels of the COF, allowing selective recognition of enantiomers through intermolecular interactions. It can be a versatile high-performance liquid chromatography (HPLC) CSP for separating a wide range of enantiomers, including chiral pharmaceutical intermediates and chiral drugs. With separation performance comparable to commercial chiral columns and even greater versatility, the PA-CA COF@SiO2 column held promise for practical applications. Chiral separation results combined with molecular simulation indicated that the mixed mode of PA and CA resulted in the broad separation capability of PA-CA COF. The introduction of the dual-chiral COFs concept opens up a new avenue for chiral recognition and separation, holding great potential for practical enantiomer separation.


Assuntos
Penicilamina , Estereoisomerismo , Cromatografia Líquida de Alta Pressão/métodos , Penicilamina/química , Penicilamina/isolamento & purificação , Cicloexilaminas/química , Cicloexilaminas/isolamento & purificação , Dióxido de Silício/química , Estruturas Metalorgânicas/química
20.
Arch Microbiol ; 206(6): 273, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38772954

RESUMO

Acid protease is widely used in industries such as food processing and feed additives. In the study, low frequency magnetic field (LF-MF) as an aid enhances acid protease production by Aspergillus niger (A. niger). The study assessed mycelial biomass, the enzymic activity of the acidic protease and underlying mechanism. At low intensities, alternating magnetic field (AMF) is more effective than static magnetic fields (SMF). Under optimal magnetic field conditions, acid protease activity and biomass increased by 91.44% and 16.31%, as compared with the control, respectively. Maximum 19.87% increase in enzyme activity after magnetic field treatment of crude enzyme solution in control group. Transcriptomics analyses showed that low frequency alternating magnetic field (LF-AMF) treatment significantly upregulated genes related to hydrolases and cell growth. Our results showed that low-frequency magnetic fields can enhance the acid protease production ability of A. niger, and the effect of AMF is better at low intensities. The results revealed that the effect of magnetic field on the metabolic mechanism of A. niger and provided a reference for magnetic field-assisted fermentation of A. niger.


Assuntos
Aspergillus niger , Campos Magnéticos , Peptídeo Hidrolases , Aspergillus niger/enzimologia , Aspergillus niger/genética , Peptídeo Hidrolases/metabolismo , Peptídeo Hidrolases/genética , Fermentação , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Biomassa , Micélio/enzimologia , Micélio/crescimento & desenvolvimento , Micélio/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...