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1.
Exp Cell Res ; 440(1): 114127, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38857839

RESUMO

CCAAT enhancer binding protein delta (CEBPD) is a transcription factor and plays an important role in apoptosis and oxidative stress, which are the main pathogenesis of ischemic stroke. However, whether CEBPD regulates ischemic stroke through targeting apoptosis and oxidative stress is unclear. Therefore, to answer this question, rat middle cerebral artery occlusion (MCAO) reperfusion model and oxygen-glucose deprivation/reoxygenation (OGD/R) primary cortical neuron were established to mimic ischemic reperfusion injury. We found that CEBPD was upregulated and accompanied with increased neurological deficit scores and infarct size, and decreased neuron in MCAO rats. The siRNA targeted CEBPD inhibited CEBPD expression in rats, and meanwhile lentivirus system was used to blocked CEBPD expression in primary neuron. CEBPD degeneration decreased neurological deficit scores, infarct size and brain water content of MCAO rats. Knockdown of CEBPD enhanced cell viability and reduced apoptosis as well as oxidative stress in vivo and in vitro. CEBPD silencing promoted the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus and the expression of heme oxygenase 1 (HO-1). Newly, CEBPD facilitated the transcription of cullin 3 (CUL3), which intensified ischemic stroke through Nrf2/HO-1 pathway that was proposed by our team in the past. In conclusion, targeting CEBPD-CUL3-Nrf2/HO-1 axis may be contributed to cerebral ischemia therapy.

2.
Int J Oncol ; 64(6)2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38757345

RESUMO

Hepatocellular carcinoma (HCC), one of the leading causes of cancer­related mortality worldwide, is challenging to identify in its early stages and prone to metastasis, and the prognosis of patients with this disease is poor. Treatment options for HCC are limited, with even radical treatments being associated with a risk of recurrence or transformation in the short term. Furthermore, the multi­tyrosine kinase inhibitors approved for first­line therapy have marked drawbacks, including drug resistance and side effects. The rise and breakthrough of immune checkpoint inhibitors (ICIs) have provided a novel direction for HCC immunotherapy but these have the drawback of low response rates. Since avoiding apoptosis is a universal feature of cancer, the induction of non­apoptotic regulatory cell death (NARCD) is a novel strategy for HCC immunotherapy. At present, NARCD pathways, including ferroptosis, pyroptosis and necroptosis, are novel potential forms of immunogenic cell death, which have synergistic effects with antitumor immunity, transforming immune 'cold' tumors into immune 'hot' tumors and exerting antitumor effects. Therefore, these pathways may be targeted as a novel treatment strategy for HCC. In the present review, the roles of ferroptosis, pyroptosis and necroptosis in antitumor immunity in HCC are discussed, and the relevant targets and signaling pathways, and the current status of combined therapy with ICIs are summarized. The prospects of targeting ferroptosis, pyroptosis and necroptosis in HCC immunotherapy are also considered.


Assuntos
Carcinoma Hepatocelular , Ferroptose , Imunoterapia , Neoplasias Hepáticas , Necroptose , Piroptose , Humanos , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Piroptose/efeitos dos fármacos , Piroptose/imunologia , Ferroptose/efeitos dos fármacos , Necroptose/imunologia , Necroptose/efeitos dos fármacos , Imunoterapia/métodos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais
3.
Sci Total Environ ; 933: 173125, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38734095

RESUMO

The abuse of antibiotics has caused the accumulation of antibiotic residues in environmental media, threatening the ecosystem and human health. Many studies on the distribution of aqueous antibiotics have been reported. However, the pollution status of antibiotics in the environment in Chinese herbal medicine planting areas is rarely comprehensively clarified, resulting in the lack of updated pollution data and conducive suggestions for ecological cultivation and sustainable development of Chinese herbal medicine. Thus, we comprehensively investigated the distribution, profiles, sources, and risks of the antibiotics in the surface water of an important tributary of the Huaihe River Basin, located in Bozhou City, a significant Chinese herbal medicine planting region. Solid-phase extraction coupled with an ultra-performance liquid chromatography-tandem mass spectrometer (SPE-UPLC-MS) was utilized to detect the antibiotics in the water. 27 kinds of antibiotics were identified with total concentrations ranging from 75.01 to 1737.99 ng·L-1, with doxycycline (DC) and doxycycline hydrochloride (DCH) possessed the highest concentration. And DC, DCH, oxilinic acid (OA), sulfamethoxazole (SMZ), clarithromycin (CLA), and roxithromycinum (ROX) were the main antibiotics detected in this basin. Correlation analysis and principal component analysis (PCA) indicated that animal husbandry was the primary source of antibiotics. Furthermore, the ecological risk assessment revealed that certain antibiotics could seriously threaten the survival of aquatic organisms, implying that local Chinese herbal medicines might be at similar growth risk. The drinking risk assessment showed that antibiotics in the water posed low risks for human, and children faced a greater drinking risk than adults. The study can help to facilitate the management of aqueous antibiotic pollution for the ecological cultivation and safe production of Chinese herbal medicine.


Assuntos
Antibacterianos , Monitoramento Ambiental , Rios , Poluentes Químicos da Água , Poluentes Químicos da Água/análise , Antibacterianos/análise , Rios/química , China , Medicamentos de Ervas Chinesas
4.
Nutrients ; 16(8)2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38674835

RESUMO

Inflammatory bowel disease (IBD) has attracted much attention worldwide due to its prevalence. In this study, the effect of a solid-in-oil-in-water (S/O/W) emulsion with Caffeic acid phenethyl ester (CAPE, a polyphenolic active ingredient in propolis) on dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice was evaluated. The results showed that CAPE-emulsion could significantly alleviate DSS-induced colitis through its effects on colon length, reduction in the disease activity index (DAI), and colon histopathology. The results of ELISA and Western blot analysis showed that CAPE-emulsion can down-regulate the excessive inflammatory cytokines in colon tissue and inhibit the expression of p65 in the NF-κB pathway. Furthermore, CAPE-emulsion promoted short-chain fatty acids production in DSS-induced colitis mice. High-throughput sequencing results revealed that CAPE-emulsion regulates the imbalance of gut microbiota by enhancing diversity, restoring the abundance of beneficial bacteria (such as Odoribacter), and suppressing the abundance of harmful bacteria (such as Afipia, Sphingomonas). The results of fecal metabolome showed that CAPE-emulsion restored the DSS-induced metabolic disorder by affecting metabolic pathways related to inflammation and cholesterol metabolism. These research results provide a scientific basis for the use of CPAE-emulsions for the development of functional foods for treating IBD.


Assuntos
Ácidos Cafeicos , Colite , Emulsões , Animais , Masculino , Camundongos , Ácidos Cafeicos/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/microbiologia , Citocinas/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Emulsões/química , Emulsões/farmacologia , Fezes/microbiologia , Fezes/química , Microbioma Gastrointestinal/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Camundongos Endogâmicos C57BL , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , Transdução de Sinais/efeitos dos fármacos
5.
Free Radic Biol Med ; 217: 116-125, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38548187

RESUMO

PURPOSE: Ferroptosis has recently been recognized as a mechanism of cerebral ischemia-reperfusion (I/R) injury, attributed to blood-brain barrier (BBB) disruption. Edaravone dexboneol (Eda.B) is a novel neuroprotective agent widely employed in ischemic stroke, which is composed of edaravone (Eda) and dexborneol. This study aimed to investigate the protective effects of Eda.B on the BBB in cerebral I/R and explore its potential mechanisms. METHODS: Transient middle cerebral artery occlusion (tMCAO) Sprague-Dawley-rats model was used. Rats were randomly assigned to sham-operated group (sham, n = 20), model group (tMCAO, n = 20), Eda.B group (Eda.B, n = 20), Eda group (Eda, n = 20) and dexborneol group (dexborneol, n = 20), and Eda.B + Zinc protoporphyria group (Eda.B + ZnPP, n = 5). Infarct area, cellular apoptosis and neurofunctional recovery were accessed through TTC staining, TUNEL staining, and modified Garcia scoring system, respectively. BBB integrity was evaluated via Evans blue staining. Nuclear factor E2 related factor 2 (Nrf-2)/heme oxygenase 1 (HO-1)/glutathione peroxidase 4 (GPX4) signaling were qualified by Western blot. Transmission electron microscopy (TEM) revealed alterations in ipsilateral brain tissue among groups. Glutathione (GSH) and malondialdehyde (MDA) levels, and Fe2+ tissue content determination were detected. RESULTS: Eda.B effectively improved neurological deficits, diminished infarct area and cellular apoptosis, as well as ameliorated BBB integrity in tMCAO rats. Further, Eda.B significantly inhibited ferroptosis, as evidenced by ameliorated pathological features of mitochondria, down-regulated of MDA and Fe2+ levels and up-regulated GSH content. Mechanistically, Eda.B attenuated BBB disruption via Nrf-2-mediated ferroptosis, promoting nuclear translocation of Nrf-2, increasing HO-1, GPX4 expression, alleviating the loss of zonula occludens 1 (ZO-1) and occludin as well as decreasing 4-hydroxynonenal (4-HNE) level. CONCLUSIONS: This study revealed for the first time that Eda.B safeguarded the BBB from cerebral I/R injury by inhibiting ferroptosis through the activation of the Nrf-2/HO-1/GPX4 axis, providing a novel insight into the neuroprotective effect of Eda.B in cerebral I/R.


Assuntos
Isquemia Encefálica , Ferroptose , Fármacos Neuroprotetores , Traumatismo por Reperfusão , Ratos , Animais , Barreira Hematoencefálica , Heme Oxigenase-1/metabolismo , Edaravone/farmacologia , Ratos Sprague-Dawley , Isquemia Encefálica/patologia , Fármacos Neuroprotetores/farmacologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Reperfusão , Traumatismo por Reperfusão/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo
6.
Int Urol Nephrol ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528290

RESUMO

Men are inevitably plagued by prostate disease throughout their lives. However, the understanding of the pathogenesis of prostate diseases is still limited. In the 1960s, McNeal proposed the theory of prostate zones: the prostate was divided into three main zones: transition zone, central zone, and peripheral zone. Over the past 50 years, significant differences between different prostate zones have been gradually revealed. We summarized the most significant differences in different zones of the prostate. For the first time, we proposed the "apparent difference in prostate zones" concept. This new concept has been proposed to understand the different zones of the prostate better. It also provided new ideas for exploring the susceptibility of lesions in different prostate zones. Despite the reported differences between zones, the treatment of prostate-related diseases remains partition agnostic. Therefore, we also discussed the clinical significance of the "apparent difference in the prostate zone" and emphasized the necessity of prostate zones.

7.
J Inflamm Res ; 17: 565-580, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38318244

RESUMO

Purpose: ST6 Beta-Galactoside Alpha-2,6-Sialyltransferase 2 (ST6GAL2), a member of the sialic acid transferase family, is differentially expressed in diverse cancers. However, it remains poorly understood in tumorigenesis and impacts on immune cell infiltration (ICI) in hepatocellular carcinoma (HCC). Patients and Methods: Herein, the expression, diagnosis, prognosis, functional enrichment, genetic alterations, immune characteristics, and targeted drugs of ST6GAL2 in HCC were researched by conducting bioinformatics analysis, in vivo, and in vitro experiments. Results: ST6GAL2 was remarkably decreased in HCC compared to non-tumor tissues, portending a poor prognosis associated with high DNA methylation levels. Functional enrichment and GSVA analyses revealed that ST6GAL2 might function through the extracellular matrix, PI3K-Akt signaling pathways, and tumor inflammation signature. We found that ST6GAL2 expression was proportional to ICI, immunostimulator, and immune subtypes. ST6GAL2 expression first increased and then decreased during the progression of liver inflammation to HCC. The dysfunctional experiment indicated that ST6GAL2 might exert immunosuppressive effects during HCC progression through regulating ICI. Several broad-spectrum anticancer drugs were obtained by drug sensitivity prediction analysis of ST6GAL2. Conclusion: In conclusion, ST6GAL2 was a reliable prognostic biomarker strongly associated with ICI, and could be a potential immunotherapeutic target for HCC.

8.
Aging Dis ; 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38300642

RESUMO

The blood-brain barrier (BBB) plays a critical role in maintaining ion and fluid homeostasis, essential for brain metabolism and neuronal function. Regulation of nutrient, water, and ion transport across the BBB is tightly controlled by specialized ion transporters and channels located within its unique cellular components. These dynamic transport processes not only influence the BBB's structure but also impact vital signaling mechanisms, essential for its optimal function. Disruption in ion, pH, and fluid balance at the BBB is associated with brain pathology and has been implicated in various neurological conditions, including stroke, epilepsy, trauma, and neurodegenerative diseases such as Alzheimer's disease (AD). However, knowledge gaps exist regarding the impact of ion transport dysregulation on BBB function in neurodegenerative dementias. Several factors contribute to this gap: the complex nature of these conditions, historical research focus on neuronal mechanisms and technical challenges in studying the ion transport mechanisms in in vivo models and the lack of efficient in vitro BBB dementia models. This review provides an overview of current research on the roles of ion transporters and channels at the BBB and poses specific research questions: 1) How are the expression and activity of key ion transporters altered in AD and vascular dementia (VaD); 2) Do these changes contribute to BBB dysfunction and disease progression; and 3) Can restoring ion transport function mitigate BBB dysfunction and improve clinical outcomes. Addressing these gaps will provide a greater insight into the vascular pathology of neurodegenerative disorders.

9.
J Sci Food Agric ; 104(9): 5462-5473, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38348948

RESUMO

BACKGROUND: Obesity has been demonstrated as a risk factor that seriously affects health. Insoluble dietary fiber (IDF), as a major component of dietary fiber, has positive effects on obesity, inflammation and diabetes. RESULTS: In this study, complex IDF was prepared using 50% enoki mushroom IDF, 40% carrot IDF, and 10% oat IDF. The effects and potential mechanism of complex IDF on obesity were investigated in C57BL/6 mice fed a high-fat diet. The results showed that feeding diets containing 5% complex IDF for 8 weeks significantly reduced mouse body weight, epididymal lipid index, and ectopic fat deposition, and improved mouse liver lipotoxicity (reduced serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase), fatty liver, and short-chain fatty acid composition. High-throughput sequencing of 16S rRNA and analysis of fecal metabolomics showed that the intervention with complex IDF reversed the high-fat-diet-induced dysbiosis of gut microbiota, which is associated with obesity and intestinal inflammation, and affected metabolic pathways, such as primary bile acid biosynthesis, related to fat digestion and absorption. CONCLUSION: Composite IDF intervention can effectively inhibit high-fat-diet-induced obesity and related symptoms and affect the gut microbiota and related metabolic pathways in obesity. Complex IDF has potential value in the prevention of obesity and metabolic syndrome. © 2024 Society of Chemical Industry.


Assuntos
Dieta Hiperlipídica , Fibras na Dieta , Microbioma Gastrointestinal , Fígado , Camundongos Endogâmicos C57BL , Obesidade , Animais , Fibras na Dieta/metabolismo , Dieta Hiperlipídica/efeitos adversos , Obesidade/metabolismo , Obesidade/dietoterapia , Obesidade/microbiologia , Camundongos , Masculino , Fígado/metabolismo , Humanos , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/metabolismo , Bactérias/genética , Fígado Gorduroso/prevenção & controle , Fígado Gorduroso/metabolismo , Fígado Gorduroso/etiologia , Avena/química , Daucus carota/química
10.
Eur J Phys Rehabil Med ; 60(1): 74-83, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37934189

RESUMO

BACKGROUND: The number of patients undergoing total knee replacement (TKR) is increasing yearly; however, there is still a relative lack of specific, individualized, and standardized protocols for functional exercise after TKR. Quantitative rehabilitation training was developed to improve the recovery of postoperative joint function, increase patient satisfaction, shorten the length of the hospital stay, improve the quality of life, and promote rapid patient recovery. AIM: We aimed to compare the effectiveness of quantitative rehabilitation training based on the enhanced recovery after surgery (ERAS) concept with conventional rehabilitation training in the early rehabilitation of patients with TKR. DESIGN: This was a single-centre, prospective, randomized controlled trial. SETTING: Inpatient department. POPULATION: Participants were patients who underwent unilateral total knee replacement. METHODS: Based on the ERAS concept, a quantitative rehabilitation training program was developed for the quantitative group, and the control group underwent conventional rehabilitation training. Seventy-eight patients undergoing TKR were randomly divided into two blinded groups: the quantitative rehabilitation group and the conventional rehabilitation group. The analysis was performed according to per-protocol practice. The primary outcome metric was the Hospital for Special Surgery Knee Score (HSS Score), and secondary outcomes included patient satisfaction, Visual Analog Pain Score (VAS), time to get out of bed for the first time after surgery, 6-minute-walk test (6MWT), quality-of-life score (SF-36), and number of days in the hospital. The incidence of postoperative complications was also recorded. RESULTS: There was no significant difference in HSS scores between the two groups before surgery (P=0.967), but the quantitative rehabilitation training group had significantly higher scores at two weeks (P=0.031), 3 months (P<0.01), and 12 months (P<0.01) after surgery than did the conventional rehabilitation training group, and both groups had higher HSS scores than before surgery. The quantitative training group had significantly higher VAS scores at 24 hours and three days postoperatively than the conventional training group (P<0.01), while there was no statistical significance at any other time points. The quantitative rehabilitation group had an earlier time to get out of bed for the first time after surgery (P<0.01), a longer 6MWT distance (P=0.028), and higher patient satisfaction and quality of life scores (SF-36) (P<0.01) that did the control group. The number of days in the hospital was lower in the quantitative training group than in the control group (P<0.001). There was no significant difference in the incidence of postoperative complications between the two groups. CONCLUSIONS: Compared with conventional rehabilitation training, quantitative rehabilitation training based on the ERAS concept was found to be safe and effective and can accelerate the recovery of joint function after surgery, shorten hospitalization time, improve patient satisfaction, and promote rapid recovery. CLINICAL REHABILITATION IMPACT: The quantitative rehabilitation training based on the ERAS concept provides a new program for rehabilitation exercises after total knee arthroplasty, which is safe and reliable, accelerates the recovery of joint function, and should be considered for clinical promotion.


Assuntos
Artroplastia do Joelho , Recuperação Pós-Cirúrgica Melhorada , Humanos , Artroplastia do Joelho/reabilitação , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento , Recuperação de Função Fisiológica , Complicações Pós-Operatórias , Articulação do Joelho
11.
J Arthroplasty ; 39(3): 665-671.e2, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37634879

RESUMO

BACKGROUND: This study aimed to compare the effectiveness of high-intensity progressive rehabilitation training with routine training in the early treatment of patients undergoing total knee arthroplasty. METHODS: There were 78 patients who underwent total knee arthroplasty and were randomized into high-intensity progressive training and routine rehabilitation training groups (RRT). The primary outcome measures were the American Hospital for Special Surgery Knee Score (HSS), with secondary outcomes including patient satisfaction, visual analog pain score, first time of standing after surgery, 6-minute walk test, 36-Item Short Form Survey (SF-36), and length of hospital stay. The incidence of postoperative complications were recorded. RESULTS: The HSS scores were higher in the intervention group at 2 weeks, 3 months, and 12 months postoperatively (P < .001). The RRT group had higher visual analog pain scores than the intervention group at 24 hours, 3 days, and 2 weeks after surgery (P < .001). The intervention group had an earlier the first time of standing after surgery and a longer 6-minute walk test distance (P < .001, P = .028, P < .001, P < .001). Patient satisfaction was higher in the intervention group, with a higher quality of life rating at 3 months postoperatively (P < .001). However, 1 year after surgery, the 2 groups had no significant differences in mental component summaries. The length of hospital stay was shorter in the intervention group than in the RRT group. CONCLUSION: Compared to routine training, high-intensity progressive rehabilitation training is more effective. It reduces postoperative patient pain, accelerates recovery of joint function, increases patient satisfaction, improves quality of life, shortens hospital stays, and promotes rapid recovery.


Assuntos
Artroplastia do Joelho , Osteoartrite do Joelho , Humanos , Artroplastia do Joelho/reabilitação , Qualidade de Vida , Resultado do Tratamento , Dor Pós-Operatória/cirurgia , Articulação do Joelho/cirurgia
12.
Environ Sci Pollut Res Int ; 30(59): 123466-123479, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37987974

RESUMO

Groundwater is an essential freshwater resource utilized in industry, agriculture, and daily life. In the Huaibei Plain (HBP), where groundwater significantly influences socio-economic development, information about its quality, hydrochemistry, and related health risks remains limited. We conducted a comprehensive groundwater sampling in the HBP and examined its rock characteristics, water quality index (WQI), and potential health risks. The results revealed that the primary factors shaping groundwater hydrochemistry were rock dissolution and weathering, cation exchange, and anthropogenic activities. WQI assessment indicated that only 73% of the groundwaters is potable, as Fe2+, Mn2+, NO3-, and F- contents in the water could pose non-carcinogenic hazards to humans. Children were more susceptible to these health risks through oral ingestion than adults. Uncertainty analysis indicated that the probabilities of non-carcinogenic risk were approximately 57% and 31% for children and adults, respectively. Sensitivity analysis further identified fluoride as the primary factor influencing non-carcinogenic risks, indicating that reducing fluoride contamination should be prioritized in future groundwater management in the HBP.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Criança , Adulto , Humanos , Monitoramento Ambiental/métodos , Fluoretos/análise , Poluentes Químicos da Água/análise , Qualidade da Água , Água Subterrânea/química , China , Medição de Risco
13.
Front Oncol ; 13: 1165732, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37456243

RESUMO

Since the theory of modern anatomical partitioning of the prostate was proposed, the differences in the incidence and pathological parameters of prostate cancer between the peripheral zone and transition zone have been gradually revealed. It suggests that there are differences in the pathogenic pathways and molecular biology of prostate cancer between different regions of origin. Over the past decade, advances in sequencing technologies have revealed more about molecules, genomes, and cell types specific to the peripheral and transitional zones. In recent years, the innovation of spatial imaging and multiple-parameter magnetic resonance imaging has provided new technical support for the zonal study of prostate cancer. In this work, we reviewed all the research results and the latest research progress in the study of prostate cancer in the past two decades. We summarized and proposed several vital issues and focused directions for understanding the differences between peripheral and transitional zones in prostate cancer.

14.
Eur J Med Res ; 28(1): 215, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37400922

RESUMO

BACKGROUND: The etiology of nonalcoholic fatty liver disease (NAFLD) involves a complex interaction of genetic and environmental factors. Previous observational studies have revealed that higher leptin levels are related to a lower risk of developing NAFLD, but the causative association remains unknown. We intended to study the causal effect between leptin and NAFLD using the Mendelian randomization (MR) study. METHODS: We performed a two-sample Mendelian randomization (TSMR) analysis using summary GWAS data from leptin (up to 50,321 individuals) and NAFLD (8,434 cases and 770,180 controls) in a European population. Instrumental variables (IVs) that satisfied the three core assumptions of Mendelian randomization were selected. The TSMR analysis was conducted using the inverse variance weighted (IVW) method, MR-Egger regression method, and weighted median (WM) method. To ensure the accuracy and stability of the study results, heterogeneity tests, multiple validity tests, and sensitivity analyses were conducted. RESULTS: The findings of the TSMR correlation analysis between NAFLD and leptin were as follows: IVW method (odds ratio (OR) 0.6729; 95% confidence interval (95% CI) 0.4907-0.9235; P = 0.0142), WM method (OR 0.6549; 95% CI 0.4373-0.9806; P = 0.0399), and MR-Egger regression method (P = 0.6920). Additionally, the findings of the TSMR correlation analysis between NAFLD and circulating leptin levels adjusted for body mass index (BMI) were as follows: IVW method (OR 0.5876; 95% CI 0.3781-0.9134; P = 0.0181), WM method (OR 0.6074; 95% CI 0.4231-0.8721; P = 0.0069), and MR-Egger regression method (P = 0.8870). It has also been shown that higher levels of leptin are causally linked to a lower risk of developing NAFLD, suggesting that leptin may serve as a protective factor for NAFLD. CONCLUSIONS: Using TSMR analysis and the GWAS database, we investigated the genetic relationship between elevated leptin levels and lowered risk of NAFLD in this study. However, further research is required to understand the underlying mechanisms.


Assuntos
Leptina , Hepatopatia Gordurosa não Alcoólica , Humanos , Leptina/genética , Análise da Randomização Mendeliana , Hepatopatia Gordurosa não Alcoólica/genética , Índice de Massa Corporal , Polimorfismo de Nucleotídeo Único/genética
15.
Am J Emerg Med ; 70: 209.e1-209.e3, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37385856

RESUMO

Crowned dens syndrome (CDS) occurs due to the deposition of calcium pyrophosphate (CPP) in the ligament tissue around the odontoid process of the axis. CDS is characterized by acute neck pain, stiffness, fever, and elevated inflammatory markers. It is a rare cause of neck pain among older people. We report a 71-year-old female patient who presented with acute neck pain, headache, with dizziness. Body temperature showed normal, with elevated C-reactive protein and ESR in the blood. Over the past 5 years, the patient has experienced neck and head pain several times.MRI of the head and CT scan of the neck showed calcification of the transverse atlantoaxial and cruciate ligament in combination with mild compression of the medulla oblongata. The patient was given non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine for 10 days, with significant symptom improvement and no recurrence at 10 months of follow-up.


Assuntos
Calcinose , Condrocalcinose , Feminino , Humanos , Idoso , Cervicalgia/etiologia , Pescoço , Calcinose/complicações , Síndrome , Cefaleia/etiologia , Erros de Diagnóstico , Condrocalcinose/diagnóstico , Condrocalcinose/diagnóstico por imagem
16.
Polymers (Basel) ; 15(12)2023 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-37376294

RESUMO

The aim of this work was to prepare insulin-loaded nanoparticles using soybean trypsin inhibitor (STI) and chitosan (CS) as a potential coating. The nanoparticles were prepared by complex coacervation, and characterized for their particle size, polydispersity index (PDI), and encapsulation efficiency. In addition, the insulin release and enzymatic degradation of nanoparticles in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) were evaluated. The results showed that the optimal conditions for preparing insulin-loaded soybean trypsin inhibitor-chitosan (INs-STI-CS) nanoparticles were as follows: CS concentration of 2.0 mg/mL, STI concentration of 1.0 mg/mL, and pH 6.0. The INs-STI-CS nanoparticles prepared at this condition had a high insulin encapsulation efficiency of 85.07%, the particle diameter size was 350 ± 5 nm, and the PDI value was 0.13. The results of the in vitro evaluation of simulated gastrointestinal digestion showed that the prepared nanoparticles could improve the stability of insulin in the gastrointestinal tract. Compared with free insulin, the insulin loaded in INs-STI-CS nanoparticles was retained at 27.71% after 10 h of digestion in the intestinal tract, while free insulin was completely digested. These findings will provide a theoretical basis for improving the stability of oral insulin in the gastrointestinal tract.

17.
Front Pharmacol ; 14: 1159094, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37361218

RESUMO

The JiGuCao capsule formula (JCF) has demonstrated promising curative effects in treating chronic hepatitis B (CHB) in clinical trials. Here, we aimed to investigate JCF's function and mechanism in diseases related to the hepatitis B virus (HBV). We used mass spectrometry (MS) to identify the active metabolites of JCF and established the HBV replication mouse model by hydrodynamically injecting HBV replication plasmids into the mice's tail vein. Liposomes were used to transfect the plasmids into the cells. The CCK-8 kit identified cell viability. We detected the levels of HBV s antigen (HBsAg) and HBV e antigen (HBeAg) by the quantitative determination kits. qRT-PCR and Western blot were used to detect the genes' expression. The key pathways and key genes related to JCF on CHB treatment were obtained by network pharmacological analysis. Our results showed that JCF accelerated the elimination of HBsAg in mice. JCF and its medicated serum inhibited HBV replication and proliferation of HBV-replicating hepatoma cells in vitro. And the key targets of JCF in treating CHB were CASP3, CXCL8, EGFR, HSPA8, IL6, MDM2, MMP9, NR3C1, PTGS2, and VEGFA. Furthermore, these key targets were related to pathways in cancer, hepatitis B, microRNAs in cancer, PI3K-Akt signaling, and proteoglycans in cancer pathways. Finally, Cholic Acid, Deoxycholic Acid, and 3', 4', 7-Trihydroxyflavone were the main active metabolites of JCF that we obtained. JCF employed its active metabolites to perform an anti-HBV effect and prevent the development of HBV-related diseases.

18.
Cell Mol Biol Lett ; 28(1): 38, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37161356

RESUMO

Prostate cancer is one of the more heterogeneous tumour types. In recent years, with the rapid development of single-cell sequencing and spatial transcriptome technologies, researchers have gained a more intuitive and comprehensive understanding of the heterogeneity of prostate cancer. Tumour-associated epithelial cells; cancer-associated fibroblasts; the complexity of the immune microenvironment, and the heterogeneity of the spatial distribution of tumour cells and other cancer-promoting molecules play a crucial role in the growth, invasion, and metastasis of prostate cancer. Single-cell multi-omics biotechnology, especially single-cell transcriptome sequencing, reveals the expression level of single cells with higher resolution and finely dissects the molecular characteristics of different tumour cells. We reviewed the recent literature on prostate cancer cells, focusing on single-cell RNA sequencing. And we analysed the heterogeneity and spatial distribution differences of different tumour cell types. We discussed the impact of novel single-cell omics technologies, such as rich omics exploration strategies, multi-omics joint analysis modes, and deep learning models, on future prostate cancer research. In this review, we have constructed a comprehensive catalogue of single-cell omics studies in prostate cancer. This article aimed to provide a more thorough understanding of the diagnosis and treatment of prostate cancer. We summarised and proposed several key issues and directions on applying single-cell multi-omics and spatial transcriptomics to understand the heterogeneity of prostate cancer. Finally, we discussed single-cell omics trends and future directions in prostate cancer.


Assuntos
Neoplasias da Próstata , Microambiente Tumoral , Masculino , Humanos , Microambiente Tumoral/genética , Neoplasias da Próstata/genética , Próstata , Células Epiteliais , Biotecnologia
19.
Polymers (Basel) ; 15(7)2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37050206

RESUMO

Supramolecular structures obtained from protein-polysaccharide association may be applied to encapsulate bioactive compounds or to improve the physical stability and texture properties of colloid-based products. In this study, the interaction of 0.1 wt% soybean trypsin inhibitor (STI) with different concentrations of chitosan (CS) in aqueous solutions was investigated under different pH by the analysis of state diagram, turbidity, zeta potential, spectroscopy, and microstructure; the protective effect of STI-CS complex coacervates on STI stability in simulated gastric juice was also discussed. The results suggested that interactions between STI and CS could form soluble/insoluble complexes mainly through hydrophobic interactions (pH 4.0) or electrostatic interactions (pH 6.0). The CD spectra showed that the secondary structure of STI did not change significantly when CS with the same charge was mixed with STI, and the secondary structure of STI was slightly changed when CS with the opposite charge was mixed with STI. Simulated gastric digestion experiments showed that the complex formed by non-covalent bonding had a protective effect on the active protein. This study provides information about the effect of different CS concentrations and pH values on the formation of complexes of CS and STI in an aqueous solution and provides theoretical references for the construction of supramolecular-structured carrier substances based on CS and STI.

20.
Opt Lett ; 48(4): 1040-1043, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36791005

RESUMO

UV-illuminated, paraelectric-phased potassium tantalate niobate (KTN) single crystals mitigate the beam deformation effects of femtosecond pulsed lasers in KTN deflectors. UV light illumination can control the amount of trapped charge present and minimize domain inversion in KTN deflectors, owing to its generated electron-hole pairs. This enables high beam quality deflection of fs pulsed lasers, with access to larger deflection angles, deflection speeds, and modulation switching ratios. These results enable the use of KTN deflectors in many fs pulsed laser applications and hasten the advancement of fs applications that require these deflection qualities.

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