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1.
J Neuroinflammation ; 21(1): 122, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720343

RESUMO

Pneumonia is a common comorbidity in patients with severe traumatic brain injury (TBI), and is associated with increased morbidity and mortality. In this study, we established a model of intratracheal Klebsiella pneumoniae administration in young adult male and female mice, at 4 days following an experimental TBI, to investigate how K. pneumoniae infection influences acute post-TBI outcomes. A dose-response curve determined the optimal dose of K. pneumoniae for inoculation (1 x 10^6 colony forming units), and administration at 4 days post-TBI resulted in transient body weight loss and sickness behaviors (hypoactivity and acute dyspnea). K. pneumoniae infection led to an increase in pro-inflammatory cytokines in serum and bronchoalveolar lavage fluid at 24 h post-infection, in both TBI and sham (uninjured) mice. By 7 days, when myeloperoxidase + neutrophil numbers had returned to baseline in all groups, lung histopathology was observed with an increase in airspace size in TBI + K. pneumoniae mice compared to TBI + vehicle mice. In the brain, increased neuroinflammatory gene expression was observed acutely in response to TBI, with an exacerbated increase in Ccl2 and Hmox1 in TBI + K. pneumoniae mice compared to either TBI or K. pneumoniae alone. However, the presence of neuroinflammatory immune cells in the injured brain, and the extent of damage to cortical and hippocampal brain tissue, was comparable between K. pneumoniae and vehicle-treated mice by 7 days. Examination of the fecal microbiome across a time course did not reveal any pronounced effects of either injury or K. pneumoniae on bacterial diversity or abundance. Together, these findings demonstrate that K. pneumoniae lung infection after TBI induces an acute and transient inflammatory response, primarily localized to the lungs with some systemic effects. However, this infection had minimal impact on secondary injury processes in the brain following TBI. Future studies are needed to evaluate the potential longer-term consequences of this dual-hit insult.


Assuntos
Lesões Encefálicas Traumáticas , Modelos Animais de Doenças , Infecções por Klebsiella , Klebsiella pneumoniae , Camundongos Endogâmicos C57BL , Animais , Lesões Encefálicas Traumáticas/microbiologia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/patologia , Camundongos , Infecções por Klebsiella/patologia , Infecções por Klebsiella/microbiologia , Feminino , Masculino , Citocinas/metabolismo , Líquido da Lavagem Broncoalveolar
2.
Small ; : e2310712, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733222

RESUMO

Extracellular vesicles (EVs) are recognized as potential candidates for next-generation drug delivery systems. However, the inherent cancer-targeting efficiency is unsatisfactory, necessitating surface modification to attach cell-binding ligands. By utilizing phospholipase D from Streptomyces in combination with maleimide-containing primary alcohol, the authors successfully anchored ligands onto milk-derived EVs (mEVs), overcoming the issues of ligand leakage or functional alteration seen in traditional methods. Quantitative nano-flow cytometry demonstrated that over 90% of mEVs are effectively modified with hundreds to thousands of ligands. The resulting mEV formulations exhibited remarkable long-term stability in conjugation proportion, ligand number, size distribution, and particle concentration, even after months of storage. It is further shown that conjugating transferrin onto mEVs significantly enhanced cellular uptake and induced pronounced cytotoxic effects when loaded with paclitaxel. Overall, this study presents a highly efficient, stable, cost-effective, and scalable ligand conjugation approach, offering a promising strategy for targeted drug delivery of EVs.

3.
Int J Mol Sci ; 25(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38731861

RESUMO

The expression of polysialic acid (polySia) on the neuronal cell adhesion molecule (NCAM) is called NCAM-polysialylation, which is strongly related to the migration and invasion of tumor cells and aggressive clinical status. Thus, it is important to select a proper drug to block tumor cell migration during clinical treatment. In this study, we proposed that lactoferrin (LFcinB11) may be a better candidate for inhibiting NCAM polysialylation when compared with CMP and low-molecular-weight heparin (LMWH), which were determined based on our NMR studies. Furthermore, neutrophil extracellular traps (NETs) represent the most dramatic stage in the cell death process, and the release of NETs is related to the pathogenesis of autoimmune and inflammatory disorders, with proposed involvement in glomerulonephritis, chronic lung disease, sepsis, and vascular disorders. In this study, the molecular mechanisms involved in the inhibition of NET release using LFcinB11 as an inhibitor were also determined. Based on these results, LFcinB11 is proposed as being a bifunctional inhibitor for inhibiting both NCAM polysialylation and the release of NETs.


Assuntos
Armadilhas Extracelulares , Lactoferrina , Moléculas de Adesão de Célula Nervosa , Ácidos Siálicos , Lactoferrina/farmacologia , Lactoferrina/metabolismo , Humanos , Armadilhas Extracelulares/metabolismo , Armadilhas Extracelulares/efeitos dos fármacos , Moléculas de Adesão de Célula Nervosa/metabolismo , Ácidos Siálicos/metabolismo , Neutrófilos/metabolismo , Neutrófilos/efeitos dos fármacos , Heparina de Baixo Peso Molecular/farmacologia
4.
Diabetol Metab Syndr ; 16(1): 101, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745237

RESUMO

BACKGROUND: The link between diabetes and dementia risk is not well understood. This study evaluates the factors linking diabetes to dementia onset, providing guidance for preventing dementia in diabetic patients. METHODS: This analysis utilized databases such as PubMed, Embase, Web of Science, and the Cochrane Library to review literature from January 31, 2012, to March 5, 2023. Articles were rigorously assessed using specific inclusion and exclusion criteria. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the studies. Data analysis was performed with STATA 15.0. RESULTS: The study analyzed 15 articles, covering 10,103,868 patients, with 8,821,516 diagnosed with diabetes. The meta-analysis reveals a substantial association between diabetes and an increased risk of dementia [RR: 1.59, 95%CI (1.40-1.80), P < 0.01, I²=96.4%]. A diabetes duration of less than five years is linked to a higher dementia risk [RR: 1.29, 95%CI (1.20-1.39), P < 0.01, I²=92.6%]. Additionally, hypoglycemia significantly raises dementia risk [RR: 1.56, 95%CI (1.13-2.16), P < 0.01, I²=51.5%]. Analyses of blood sugar control, glycated hemoglobin, and fasting blood sugar indicated no significant effects on the onset of dementia. CONCLUSION: Diabetes notably increases dementia risk, particularly where diabetes duration is under five years or hypoglycemia is present. REGISTRATION: The research protocol was registered with PROSPERO and assigned the registration number CRD42023394942.

5.
BMC Pulm Med ; 24(1): 236, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745304

RESUMO

BACKGROUND: We studied whether the exercise improves cigarette smoke (CS) induced chronic obstructive pulmonary disease (COPD) in mice through inhibition of inflammation mediated by Wnt/ß-catenin-peroxisome proliferator-activated receptor (PPAR) γ signaling. METHODS: Firstly, we observed the effect of exercise on pulmonary inflammation, lung function, and Wnt/ß-catenin-PPARγ. A total of 30 male C57BL/6J mice were divided into the control group (CG), smoke group (SG), low-intensity exercise group (LEG), moderate-intensity exercise group (MEG), and high-intensity exercise group (HEG). All the groups, except for CG, underwent whole-body progressive exposure to CS for 25 weeks. Then, we assessed the maximal exercise capacity of mice from the LEG, MEG, and HEG, and performed an 8-week treadmill exercise intervention. Then, we used LiCl (Wnt/ß-catenin agonist) and XAV939 (Wnt/ß-catenin antagonist) to investigate whether Wnt/ß-catenin-PPARγ pathway played a role in the improvement of COPD via exercise. Male C57BL/6J mice were randomly divided into six groups (n = 6 per group): CG, SG, LiCl group, LiCl and exercise group, XAV939 group, and XAV939 and exercise group. Mice except those in the CG were exposed to CS, and those in the exercise groups were subjected to moderate-intensity exercise training. All the mice were subjected to lung function test, lung histological assessment, and analysis of inflammatory markers in the bronchoalveolar lavage fluid, as well as detection of Wnt1, ß-catenin and PPARγ proteins in the lung tissue. RESULTS: Exercise of various intensities alleviated lung structural changes, pulmonary function and inflammation in COPD, with moderate-intensity exercise exhibiting significant and comprehensive effects on the alleviation of pulmonary inflammation and improvement of lung function. Low-, moderate-, and high-intensity exercise decreased ß-catenin levels and increased those of PPARγ significantly, and only moderate-intensity exercise reduced the level of Wnt1 protein. Moderate-intensity exercise relieved the inflammation aggravated by Wnt agonist. Wnt antagonist combined with moderate-intensity exercise increased the levels of PPARγ, which may explain the highest improvement of pulmonary function observed in this group. CONCLUSIONS: Exercise effectively decreases COPD pulmonary inflammation and improves pulmonary function. The beneficial role of exercise may be exerted through Wnt/ß-catenin-PPARγ pathway.


Assuntos
Camundongos Endogâmicos C57BL , PPAR gama , Condicionamento Físico Animal , Doença Pulmonar Obstrutiva Crônica , Via de Sinalização Wnt , Animais , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Masculino , Via de Sinalização Wnt/fisiologia , Camundongos , Condicionamento Físico Animal/fisiologia , PPAR gama/metabolismo , Modelos Animais de Doenças , Pulmão/metabolismo , Pulmão/fisiopatologia , Inflamação/metabolismo
6.
Shock ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38713552

RESUMO

OBJECTIVE: This study aimed to investigate the effect of the central venous-to-arterial carbon dioxide partial pressure difference (Pcv-aCO2) on the administration of cardiotonic drugs in patients with early-stage septic shock. METHODS: A retrospective study was conducted on 120 patients suffering from septic shock. At admission, the left ventricular ejection fraction (LVEF) and Pcv-aCO2 of the patients were obtained. On the premise of mean arterial pressure (MAP) ≥ 65 mmHg, the patients were divided into two groups according to the treatment approaches adopted by different doctors-Control group: LVEF ≤50%; Observation group: Pcv-aCO2 ≥ 6. Both groups received cardiotonic therapy. RESULTS: The two groups of patients had similar general conditions and pre-resuscitation conditions (P > 0.05). Compared to the Control group, the Observation group had a higher MAP, Lac clearance rate, and urine output after six hours of resuscitation (P < 0.05), but a lower absolute value of Lac, total fluid intake in 24 hours, and a lower number of patients receiving renal replacement therapy during hospitalization (P < 0.05). After six hours of resuscitation, the percentages of patients meeting central venous oxygen saturation and central venous pressure targets were not significantly different between the Control and Observation groups (P > 0.05). There was no difference in the 28-day mortality rate between the two groups (P > 0.05). CONCLUSION: Pcv-aCO2 is more effective than LVEF in guiding the administration of cardiotonic drugs in the treatment of patients with septic shock.

7.
Eur J Radiol ; 176: 111495, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38714134

RESUMO

PURPOSE: To investigate the association between the intravascular enhancement sign (IVES) and intraluminal thrombus (ILT) detected by high-resolution magnetic resonance vessel wall imaging (HR-VWI) in patients with middle cerebral artery (MCA) atherosclerosis. METHOD: The data of patients who underwent HR-VWI between May 2021 and May 2023, including clinical information, the number of IVES vessels, stenosis degree, ILT, plaque features on 3D T1-weighted turbo spin echo sequences, and signal intensity ratio (SIR) on 3D time-of-flight magnetic resonance angiography, were retrospectively analyzed. Correlation and logistic regression analyses were performed. RESULTS: A total of 194 MCA plaques were identified in 132 patients (103 [53 %] on the left). Atherosclerosis with, relative to without, ILT was associated with a higher incidence of ischemic events, higher plaque enhancement and stenosis degrees, more vessels with IVES, and lower remodeling ratio, lumen area, wall area, total vessel area, and SIR. Multivariate logistic regression analysis showed significant and independent associations of the number of IVES vessels (OR = 1.089; 95 % CI [1.013-1.170]; P = 0.020) and SIR (OR = 0.007; 95 % CI [0.0004-0.124]; P < 0.001) with ILT. The number of vessels with the IVES (AUC = 0.81, 95 % CI [0.75-0.87]; P < 0.001) and SIR (AUC = 0.88, 95 % CI [0.82-0.94]; P < 0.001) sufficiently diagnosed ILT, and the AUC of the combination of the IVES and SIR was 0.89 (95 % CI [0.84-0.94]; P < 0.001). CONCLUSION: The number of IVES vessels and SIR are independent risk factors for ILT. They may provide new monitoring targets for stroke prevention in patients with atherosclerotic stenosis.

8.
Ann Hematol ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691144

RESUMO

Refractory/relapsed idiopathic multicentric Castleman disease (R/R iMCD) has limited treatment options. With studies showing increased mTOR activation in iMCD patients, sirolimus becomes an attractive and promising therapy for R/R iMCD. Here we report the results of a retrospective study involving 26 R/R iMCD patients treated with sirolimus-containing regimen. The median age at sirolimus initiation was 40.5 years (23-60), with a median prior treatment line of 2 (1-5). 18 patients (69.2%) achieved symptomatic and biochemical response, with a median time to at least overall partial remission of 1.9 months (0.5-14.6). The median follow-up time from sirolimus initiation was 11.7 months (1.6-50.7) and the median time to next treatment (TTNT) was 46.2 months. No patients died at the end of follow-up. Most of the patients in the cohort are in ongoing responses and continue sirolimus therapy. Sirolimus is well tolerated with minor adverse effects. In conclusion, sirolimus is effective for R/R iMCD patients with good tolerance.

9.
Infect Agent Cancer ; 19(1): 21, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693556

RESUMO

AIMS: This study compared the prevalences of metabolic syndrome and of cardiac or kidney comorbidities among patients with hepatocellular carcinoma (HCC) associated with metabolic dysfunction-related fatty liver disease (MAFLD), chronic infection with hepatitis B or C virus (HBV or HCV), or the combination of MAFLD and chronic HBV infection. METHODS: Medical records were retrospectively analyzed for patients with HCC who underwent hepatectomy between March 2013 and March 2023. Patients with HCC of different etiologies were compared in terms of their clinicodemographic characteristics and laboratory data before surgery. RESULTS: Of the 2422 patients, 1,822 (75.2%) were chronically infected with HBV without MAFLD and HCV, 415 (17.2%) had concurrent MAFLD and chronic HBV infection but no HCV infection, 121 (5.0%) had MAFLD without hepatitis virus infection, and 64 (2.6%) were chronically infected with HCV in the presence or absence of MAFLD and HBV infection. Compared to patients chronically infected with HBV without MAFLD and HCV, those with MAFLD but no hepatitis virus infection showed significantly lower prevalence of cirrhosis, ascites, portal hypertension, alpha-fetoprotein concentration ≥ 400 ng/mL, tumor size > 5 cm, multinodular tumors and microvascular invasion. Conversely, they showed significantly higher prevalence of metabolic syndrome, hypertension, type 2 diabetes, abdominal obesity, history of cardiovascular disease, T-wave alterations, hypertriglyceridemia and hyperuricemia, as well as higher risk of arteriosclerotic cardiovascular disease. Compared to patients with MAFLD but no hepatitis virus infection, those with concurrent MAFLD and chronic infection with HBV showed significantly higher prevalence of cirrhosis, ascites and portal hypertension, but significantly lower prevalence of hypertension and history of cardiovascular disease. Compared to patients with other etiologies, those chronically infected with HCV in the presence or absence of MAFLD and HBV infection, showed significantly higher prevalence of cirrhosis, portal hypertension, ascites, and esophagogastric varices. CONCLUSION: Patients with HCC associated with MAFLD tend to have a background of less severe liver disease than those with HCC of other etiologies, but they may be more likely to suffer metabolic syndrome or comorbidities affecting the heart or kidneys.

10.
Mol Plant Pathol ; 25(5): e13462, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38695630

RESUMO

MicroRNAs (miRNAs) are widely involved in various biological processes of plants and contribute to plant resistance against various pathogens. In this study, upon sugarcane mosaic virus (SCMV) infection, the accumulation of maize (Zea mays) miR398b (ZmmiR398b) was significantly reduced in resistant inbred line Chang7-2, while it was increased in susceptible inbred line Mo17. Degradome sequencing analysis coupled with transient co-expression assays revealed that ZmmiR398b can target Cu/Zn-superoxidase dismutase2 (ZmCSD2), ZmCSD4, and ZmCSD9 in vivo, of which the expression levels were all upregulated by SCMV infection in Chang7-2 and Mo17. Moreover, overexpressing ZmmiR398b (OE398b) exhibited increased susceptibility to SCMV infection, probably by increasing reactive oxygen species (ROS) accumulation, which were consistent with ZmCSD2/4/9-silenced maize plants. By contrast, silencing ZmmiR398b (STTM398b) through short tandem target mimic (STTM) technology enhanced maize resistance to SCMV infection and decreased ROS levels. Interestingly, copper (Cu)-gradient hydroponic experiments demonstrated that Cu deficiency promoted SCMV infection while Cu sufficiency inhibited SCMV infection by regulating accumulations of ZmmiR398b and ZmCSD2/4/9 in maize. These results revealed that manipulating the ZmmiR398b-ZmCSD2/4/9-ROS module provides a prospective strategy for developing SCMV-tolerant maize varieties.


Assuntos
Resistência à Doença , MicroRNAs , Doenças das Plantas , Potyvirus , Zea mays , Zea mays/virologia , Zea mays/genética , Potyvirus/fisiologia , Potyvirus/patogenicidade , Doenças das Plantas/virologia , Doenças das Plantas/genética , Resistência à Doença/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Regulação da Expressão Gênica de Plantas , Espécies Reativas de Oxigênio/metabolismo
11.
Orphanet J Rare Dis ; 19(1): 185, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698461

RESUMO

BACKGROUND: Cryoglobulinemia with pulmonary involvement is rare, and its characteristics, radiological findings, and outcomes are still poorly understood. METHODS: Ten patients with pulmonary involvement of 491 cryoglobulinemia patients at Peking Union Medical College Hospital were enrolled in this retrospective study. We analyzed the characteristics, radiological features and management of pulmonary involvement patients, and compared with those of non-pulmonary involvement with cryoglobulinemia. RESULTS: The 10 patients with pulmonary involvement (2 males; median age, 53 years) included three patients with type I cryoglobulinemia and seven patients with mixed cryoglobulinemia. All of 10 patients were IgM isotype cryoglobulinemia. All type I patients were secondary to B-cell non-Hodgkin lymphoma. Four mixed patients were essential, and the remaining patients were secondary to infections (n = 2) and systemic lupus erythematosus (n = 1), respectively. Six patients had additional affected organs, including skin (60%), kidney (50%), peripheral nerves (30%), joints (20%), and heart (20%). The pulmonary symptoms included dyspnea (50%), dry cough (30%), chest tightness (30%), and hemoptysis (10%). Chest computed tomography (CT) showed diffuse ground-glass opacity (80%), nodules (40%), pleural effusions (30%), and reticulation (20%). Two patients experienced life-threatening diffuse alveolar hemorrhage. Five patients received corticosteroid-based regimens, and four received rituximab-based regimens. All patients on rituximab-based regimens achieved clinical remission. The estimated two-year overall survival (OS) was 40%. Patients with pulmonary involvement had significantly worse OS and progression-free survival than non-pulmonary involvement patients of cryoglobulinemia (P < 0.0001). CONCLUSIONS: A diagnosis of pulmonary involvement should be highly suspected for patients with cryoglobulinemia and chest CT-indicated infiltrates without other explanations. Patients with pulmonary involvement had a poor prognosis. Rituximab-based treatment may improve the outcome.


Assuntos
Crioglobulinemia , Humanos , Crioglobulinemia/patologia , Crioglobulinemia/diagnóstico por imagem , Crioglobulinemia/complicações , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Idoso , Adulto , Tomografia Computadorizada por Raios X , Pneumopatias/diagnóstico por imagem , Pneumopatias/patologia , Pneumopatias/tratamento farmacológico , Pulmão/diagnóstico por imagem , Pulmão/patologia
12.
Nucl Med Commun ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38745523

RESUMO

INTRODUCTION: It is important to distinguish Waldenström macroglobulinemia from smoldering Waldenström macroglobulinemia (sWM), because only patients with Waldenström macroglobulinemia require treatment, however the distinction can be clinically complex. The aim of this study is to investigate whether [68Ga]Ga-pentixafor PET/CT shows different characteristics in sWM and Waldenström macroglobulinemia patients and therefore can help to differentiate Waldenström macroglobulinemia and sWM. RESULTS: Thirty-seven patients with newly diagnosed Waldenström macroglobulinemia and 11 sWM patients were analyzed [35 men and 13 women; 64.3 ±â€…10.7 (range, 29-87) years old]. The SUVmax of bone marrow disease, lymph nodes, and other extramedullary diseases on [68Ga]Ga-pentixafor were significantly higher than those on 2-[18F]FDG PET/CT (P < 0.05). On [68Ga]Ga-pentixafor PET/CT, patients with Waldenström macroglobulinemia had more lymph node regions involved, significantly higher incidence of involvement in more than three lymph node regions, larger nodal disease, and higher incidence of other extramedullary disease when compared with sWM patients (P < 0.05). Waldenström macroglobulinemia patients showed significantly higher total lesions uptake, total lesion volume, and SUVmax of extramedullary disease than sWM patients did (P < 0.05). None of the visual or semiquantitative indexes in 2-[18F]FDG PET/CT showed significant difference between Waldenström macroglobulinemia and sWM patients. CONCLUSION: [68Ga]Ga-pentixafor PET/CT had better diagnostic performance than 2-[18F]FDG PET/CT in Waldenström macroglobulinemia. Patients with Waldenström macroglobulinemia presented with more extensive extramedullary disease shown in [68Ga]Ga-pentixafor PET/CT than sWM patients did.

13.
Langmuir ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38743441

RESUMO

The exploration of environmentally friendly, less toxic, sustained-release insecticide is increasing with the growing demand for food to meet the requirements of the expanding population. As a sustained-release carrier, the unique, environmentally friendly intelligent responsive hydrogel system is an important factor in improving the efficiency of insecticide utilization and accurate release. In this study, we developed a facile approach for incorporating the natural compound rosin (dehydroabietic acid, DA) and zinc ions (Zn2+) into a poly(N-isopropylacrylamide) (PNIPAM) hydrogel network to construct a controlled-release hydrogel carrier (DA-PNIPAM-Zn2+). Then, the model insecticide avermectin (AVM) was encapsulated in the carrier at a drug loading rate of 36.32% to form AVM@DA-PNIPAM-Zn2+. Surprisingly, the smart controlled carrier exhibited environmental responsiveness, strongly enhanced mechanical properties, self-healing ability, hydrophobicity, and photostability to ensure a balance between environmental friendliness and the precision of the drug release. The release experiments showed that the carboxyl and amide groups in the polymer chains alter the intermolecular forces within the hydrogel meshes and ingredient diffusion by changing temperatures (25 and 40 °C) and pH values (5.8, 7.4, and 8.5), leading to different release behaviors. The insecticidal activity of the AVM@DA-PNIPAM-Zn2+ against oriental armyworms was good, with an effective minimum toxicity toward aquatic animals. Therefore, AVM@DA-PNIPAM-Zn2+ is an effective drug delivery system against oriental armyworms. We anticipate that this ecofriendly, sustainable, smart-response carrier may broaden the utilization rosin and its possible applications in the agricultural sector.

14.
Front Immunol ; 15: 1360132, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38707908

RESUMO

Introduction: Considerable evidence has unveiled a potential correlation between gut microbiota and spinal degenerative diseases. However, only limited studies have reported the direct association between gut microbiota and spinal stenosis. Hence, in this study, we aimed to clarify this relationship using a two-sample mendelian randomization (MR) approach. Materials and Methods: Data for two-sample MR studies was collected and summarized from genome-wide association studies (GWAS) of gut microbiota (MiBioGen, n = 13, 266) and spinal stenosis (FinnGen Biobank, 9, 169 cases and 164, 682 controls). The inverse variance-weighted meta-analysis (IVW), complemented with weighted median, MR-Egger, weighted mode, and simple mode, was used to elucidate the causality between gut microbiota and spinal stenosis. In addition, we employed mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and the MR-Egger intercept test to assess horizontal multiplicity. Cochran's Q test to evaluate heterogeneity, and "leave-one-out" sensitivity analysis to determine the reliability of causality. Finally, an inverse MR analysis was performed to assess the reverse causality. Results: The IVW results indicated that two gut microbial taxa, the genus Eubacterium fissicatena group and the genus Oxalobacter, have a potential causal relationship with spinal stenosis. Moreover, eight potential associations between genetic liability of the gut microbiota and spinal stenosis were implied. No significant heterogeneity of instrumental variables or horizontal pleiotropy were detected. In addition, "leave-one-out" sensitivity analysis confirmed the reliability of causality. Finally, the reverse MR analysis revealed that no proof to substantiate the discernible causative relationship between spinal stenosis and gut microbiota. Conclusion: This analysis demonstrated a possible causal relationship between certain particular gut microbiota and the occurrence of spinal stenosis. Further studies focused on the mechanism of gut microbiota-mediated spinal stenosis can lay the groundwork for targeted prevention, monitoring, and treatment of spinal stenosis.


Assuntos
Microbioma Gastrointestinal , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Estenose Espinal , Humanos , Microbioma Gastrointestinal/genética , Estenose Espinal/genética , Estenose Espinal/microbiologia , Predisposição Genética para Doença
15.
Eur J Neurosci ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711292

RESUMO

A mounting body of evidences suggests that patients with chronic heart failure (HF) frequently experience cognitive impairments, but the neuroanatomical mechanism underlying these impairments remains elusive. In this retrospective study, 49 chronic HF patients and 49 healthy controls (HCs) underwent brain structural MRI scans and cognitive assessments. Cortical morphology index (cortical thickness, complexity, sulcal depth and gyrification) were evaluated. Correlations between cortical morphology and cognitive scores and clinical variables were explored. Logistic regression analysis was employed to identify risk factors for predicting 3-year major adverse cardiovascular events. Compared with HCs, patients with chronic HF exhibited decreased cognitive scores (p < .001) and decreased cortical thickness, sulcal depth and gyrification in brain regions involved cognition, sensorimotor, autonomic nervous system (family-wise error correction, all p values <.05). Notably, HF duration and New York Heart Association (NYHA) demonstrated negative correlations with abnormal cortex morphology, particularly HF duration and thickness in left precentral gyrus (r = -.387, p = .006). Cortical morphology characteristics exhibited positive associations with global cognition, particularly cortical thickness in left pars opercularis (r = .476, p < .001). NYHA class is an independent risk factor for adverse outcome (p = .001). The observed correlation between abnormal cortical morphology and global cognition suggested that cortical morphology may serve as a promising imaging biomarker and provide insights into neuroanatomical underpinnings of cognitive impairment in patients with chronic HF.

17.
Epilepsia Open ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727134

RESUMO

OBJECTIVE: Hospital-acquired infections are a common complication for patients with moderate or severe traumatic brain injury (TBI), contributing to morbidity and mortality. As infection-mediated immune responses can predispose towards epilepsy, we hypothesized that post-injury hospital-acquired infections increase the risk of post-traumatic epilepsy (PTE). METHODS: A retrospective cohort study of adults with moderate to severe TBI was conducted using data from the Victorian State Trauma Registry in Australia. Infections were identified from the International Statistical Classification of Diseases and Related Health Problems 10th Revision-Australian Modification (ICD-10-AM) codes, and diagnosis of PTE was determined by the Glasgow Outcome Scale - Extended questionnaire regarding epileptic fits at 24 months follow-up. RESULTS: Of all TBI patients (n = 15 152), 24% had evidence of having had any type of infection, with the most common being pneumonia, urinary tract, and respiratory infections. Of those who responded to the PTE question at 24 months (n = 1361), 11% had developed PTE. Univariable analysis found that the incidence of PTE was higher in patients who had any type of infection compared to patients without an infection (p < 0.001). After adjustment for covariates associated with both development of PTE and risk of infection, multivariable analysis found a solid association between infection and PTE (adjusted RR = 1.59; 95% CI: 1.11-2.28; p = 0.011). Having any type of complicating infection acquired during admission was also associated with poor GOSE outcomes at subsequent follow-ups (adjusted OR = 0.20; 95% CI: 0.11-0.35, p < 0.001). SIGNIFICANCE: These findings suggest that hospital-acquired infections contribute to PTE development after TBI. Future investigation into infections as a modifiable target to reduce poor outcomes after TBI is warranted. PLAIN LANGUAGE SUMMARY: Hospital-acquired infections are common in patients with traumatic brain injuries. A database study of adults with moderate or severe brain injuries in Australia examined whether these infections are associated with the development of epilepsy after a brain injury. 24% of patients had infections, with pneumonia and urinary tract infections being the most common. Of those surveyed 2 years after the injury, 11% developed post-traumatic epilepsy. Patients with infections had a significantly higher risk of epilepsy, even when accounting for other known risk factors, and infections were also linked to poor outcomes more broadly. The study suggests that preventing hospital-acquired infections could be a crucial target for improving outcomes after traumatic brain injuries.

18.
Biomed Mater ; 19(4)2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38697132

RESUMO

During the process of malignant tumor treatment, photodynamic therapy (PDT) exerts poor efficacy due to the hypoxic environment of the tumor cells, and long-time chemotherapy reduces the sensitivity of tumor cells to chemotherapy drugs due to the presence of drug-resistant proteins on the cell membranes for drug outward transportation. Therefore, we reported a nano platform based on mesoporous silica coated with polydopamine (MSN@PDA) loading PDT enhancer MnO2, photosensitizer indocyanine green (ICG) and chemotherapeutic drug doxorubicin (DOX) (designated as DMPIM) to achieve a sequential release of different drugs to enhance treatment of malignant tumors. MSN was first synthesized by a template method, then DOX was loaded into the mesoporous channels of MSN, and locked by the PDA coating. Next, ICG was modified by π-π stacking on PDA, and finally, MnO2layer was accumulated on the surface of DOX@MSN@PDA- ICG@MnO2, achieving orthogonal loading and sequential release of different drugs. DMPIM first generated oxygen (O2) through the reaction between MnO2and H2O2after entering tumor cells, alleviating the hypoxic environment of tumors and enhancing the PDT effect of sequentially released ICG. Afterwards, ICG reacted with O2in tumor tissue to produce reactive oxygen species, promoting lysosomal escape of drugs and inactivation of p-glycoprotein (p-gp) on tumor cell membranes. DOX loaded in the MSN channels exhibited a delay of approximately 8 h after ICG release to exert the enhanced chemotherapy effect. The drug delivery system achieved effective sequential release and multimodal combination therapy, which achieved ideal therapeutic effects on malignant tumors. This work offers a route to a sequential drug release for advancing the treatment of malignant tumors.


Assuntos
Doxorrubicina , Liberação Controlada de Fármacos , Verde de Indocianina , Indóis , Compostos de Manganês , Óxidos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Polímeros , Fotoquimioterapia/métodos , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/administração & dosagem , Verde de Indocianina/química , Indóis/química , Animais , Compostos de Manganês/química , Humanos , Polímeros/química , Linhagem Celular Tumoral , Óxidos/química , Fármacos Fotossensibilizantes/química , Dióxido de Silício/química , Camundongos , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Portadores de Fármacos/química , Porosidade
19.
Environ Res ; 252(Pt 3): 118982, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38697598

RESUMO

The surge in non-grain production on farmland (NGPF) poses significant threats to food security and land sustainability, particularly in hilly regions. However, there remains a lack of clarity on how to effectively balance grain and non-grain production in relation to land remediation. Using Wannian County as a case study, we investigate the evolution of this by leveraging high-precision land surveys and satellite imagery. Through the application of bootstrapped partial linear regression models, we identify key influencers behind each type of NGPF. In proposing land remediation solutions, we integrate the results of NGPF and land quality evaluations to identify mismatches between non-grain production and land attributes (i.e., topography, geology, soil, and land use). Our findings reveal a substantial growth in NGPF, expanding from 3838.72 ha to 5659.64 ha (2010-2020), and predominantly occurring on farmland with favorable natural conditions and connected locations such as proximity to roads, town centers, and industrial plants. Surprisingly, the basic farmland protection policy shows limited effectiveness in curbing NGPF, except for garden operations. We identify 1674 NGPF patches suitable for conversion to grain production and provide land remediation suggestions tailored to low-quality farmland with specific natural barriers, thus complementing the demand for regional non-grain production. This study thereby innovatively proposes nature-based land remediation strategies to address the non-grain production dilemma by tailoring NGPF and land quality, offering valuable insights for sustainable farmland management in China and beyond.

20.
Sci Total Environ ; 931: 172973, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38705294

RESUMO

In this work, corn straw was used as raw material, Hummers method and activation were used to adjust the graphite structure in biochar, and preparing straw based biochar (H-BCS) with ultra-high specific surface area (3441.80 m2/g), highly total pore volume (1.9859 cm3/g), and further enhanced physicochemical properties. Compared with untreated straw biochar (BCS), the specific surface area and total pore volume of H-BCS were increased by 47.24 % and 55.85 %, respectively. H-BCS showed good removal ability in subsequent experiments by using chloramphenicol (CP), hexavalent chromium (Cr6+), and crystal violet (CV) as adsorption models. In addition, the adsorption capacities of H-BCS (CP: 1396.30 mg/g, Cr6+: 218.40 mg/g, and CV: 1246.24 mg/g) are not only higher than most adsorbents, even after undergoing 5 cycles of regeneration, its adsorption capacity remains above 80 %, indicating significant potential for practical applications. In addition, we also speculated and analyzed the conjecture about the "graphite-structure regulation" during the preparation process, and finally discussed the possible mechanism during the adsorption processes. We hope this work could provide a new strategy to solve the restriction of biochar performance by further exploring the regulation of graphite structure in carbon materials.

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