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1.
J Environ Sci (China) ; 147: 474-486, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39003063

RESUMO

Nano zero-valent iron (nZVI) is widely used in soil remediation due to its high reactivity. However, the easy agglomeration, poor antioxidant ability and passivation layer of Fe-Cr coprecipitates of nZVI have limited its application scale in Cr-contaminated soil remediation, especially in high concentration of Cr-contaminated soil. Herein, we found that the carboxymethyl cellulose on nZVI particles could increase the zeta potential value of soil and change the phase of nZVI. Along with the presence of biochar, 97.0% and 96.6% Cr immobilization efficiency through CMC-nZVI/BC were respectively achieved in high and low concentrations of Cr-contaminated soils after 90-days remediation. In addition, the immobilization efficiency of Cr(VI) only decreased by 5.1% through CMC-nZVI/BC treatment after 10 weeks aging in air, attributing to the strong antioxidation ability. As for the surrounding Cr-contaminated groundwater, the Cr(VI) removal capacity of CMC-nZVI/BC was evaluated under different reaction conditions through column experiments and COMSOL Multiphysics. CMC-nZVI/BC could efficiently remove 85% of Cr(VI) in about 400 hr when the initial Cr(VI) concentration was 40 mg/L and the flow rate was 0.5 mL/min. This study demonstrates that uniformly dispersed CMC-nZVI/BC has an excellent remediation effect on different concentrations of Cr-contaminated soils.


Assuntos
Carboximetilcelulose Sódica , Carvão Vegetal , Cromo , Recuperação e Remediação Ambiental , Ferro , Poluentes do Solo , Poluentes do Solo/química , Carvão Vegetal/química , Recuperação e Remediação Ambiental/métodos , Ferro/química , Cromo/química , Carboximetilcelulose Sódica/química , Solo/química , Nanopartículas Metálicas/química
2.
Diagn Cytopathol ; 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38970451

RESUMO

BACKGROUND: To explore the value of cell morphology, immunophenotype, and gene alterations of serosal effusion in the diagnosis of lymphoma. METHODS: Serosal effusion of 69 cases of lymphoma patients were collected, including 36 cases with malignant effusion and 33 cases with nonmalignant effusion. Ordinary cytology, liquid-based cytology, cellblock, and immunocytochemical staining were performed in each case, some cases were detected by fluorescence in situ hybridization for C-MYC, BCL2, and BCL6 gene translocations. T/B cell ratio in malignant and nonmalignant serosal effusions was analyzed and compared by flow cytometry (FCM) and immunohistochemical (IHC), respectively. The prognostic value of serous effusion in diffuse large B-cell lymphoma (DLBCL) was investigated and another 20 DLBCL cases without effusion were successively selected as control. RESULTS: The number of naive lymphocytes, apoptotic bodies, and mitotic figures were more common in malignant effusions compared with nonmalignant effusions (p < .01). The top three lymphomas in malignant effusion were DLBCL (19/36, 52.8%), mantle cell lymphoma (MCL) (4/36, 11.1%, 3 blastoid variant) and high-grade B-cell lymphoma (HGBL) (4/36, 11.1%). T/B cell ratio by FCM analysis ranged from 0.00 to 0.55 (mean 0.084) in malignant effusion, and 2.58 to 984.00 (mean 249.9) in nonmalignant effusion. The difference was significant (p = .017). The T/B cell ratio by IHC analysis ranged from 0.02 to 3.00 (mean 0.200) in malignant effusion, and 2.00-100.00 (mean 34.10) in nonmalignant effusion. The difference was significant (p = .017). In the effusions involving DLBCL, most effusions were present at the time of diagnosis (57.9%); single pleural effusions were more common (36.8%). The median overall survival times of patients with malignant effusion, nonmalignant effusion and DLBCL without serous effusion were 11, 17, and 23 months respectively (p = .04). Three patients of HGBL died, and the overall survival times were 5, 8, and 9 months, respectively. CONCLUSIONS: The cytomorphological characteristics combined with immunophenotype, FCM, gene rearrangement, and other tests can diagnose and classify patients with effusion as the first symptom. The T/B cell ratio is less than 1 by FCM or IHC suggesting a malignant serosal effusion. The presence of malignant effusion in DLBCL patients is an important clue for poor prognosis.

3.
Front Endocrinol (Lausanne) ; 15: 1416287, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966219

RESUMO

Primary aldosteronism (PA) is a common cause of secondary hypertension. Adrenalectomy is an effective treatment for unilateral PA, particularly aldosterone-producing adenoma (APA), resulting in improvements in biochemical parameters and blood pressure in the vast majority of patients. The article provides a comprehensive overview of PA, focusing on the outcomes of adrenalectomy for PA and the factors that may suggest prognostic implications. Analysis of the outcome of different PA patients undergoing adrenalectomy in terms of preoperative factors, vascular and adipose conditions, type of pathology, and somatic variants. In addition, it is recommended to use the histopathology of primary aldosteronism (HISTALDO) consensus to classify the patient's pathological type, with classical and nonclassical pathological types showing a different prognosis and possibly being associated with an unresected contralateral adrenal gland. The primary aldosteronism surgical outcome (PASO) consensus sets uniform standards for postoperative outcomes in unilateral PA, but its setting of thresholds remains controversial. Partial adrenalectomy shows similar surgical results and fewer postoperative complications than total adrenalectomy, but there is a risk of missing the true source of abnormal aldosterone secretion. Steroid profiling and functional imaging techniques offer alternative options to adrenal vein sampling (AVS) for unilateral and bilateral judgments in patients with PA. A combination of factors is needed to predict the prognosis of PA patients undergoing adrenalectomy in order to manage patient expectations of the outcome of the procedure and to closely monitor blood pressure and biochemical parameters in patients who suggest a poorer prognosis.


Assuntos
Adrenalectomia , Hiperaldosteronismo , Hiperaldosteronismo/cirurgia , Humanos , Prognóstico , Resultado do Tratamento , Aldosterona/sangue , Aldosterona/metabolismo , Hipertensão/cirurgia , Hipertensão/etiologia
4.
Front Immunol ; 15: 1417758, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38983854

RESUMO

Exosomes represent a type of extracellular vesicles derived from the endosomal pathway that transport diverse molecular cargoes such as proteins, lipids, and nucleic acids. These cargoes have emerged as crucial elements impacting disease diagnosis, treatment, and prognosis, and are integral to the process of exosome formation. This review delves into the essential molecular cargoes implicated in the phases of exosome production and release. Emphasis is placed on their significance as cancer biomarkers and potential therapeutic targets, accompanied by an exploration of the obstacles and feasible applications linked to these developments.


Assuntos
Exossomos , Neoplasias , Exossomos/metabolismo , Humanos , Neoplasias/diagnóstico , Neoplasias/metabolismo , Animais , Biomarcadores Tumorais/metabolismo
5.
Int Immunopharmacol ; 138: 112595, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38950455

RESUMO

Periodontitis is a chronic inflammatory disease and is the primary contributor to adult tooth loss. Diabetes exacerbates periodontitis, accelerates periodontal bone resorption. Thus, effectively managing periodontitis in individuals with diabetes is a long-standing challenge. This review introduces the etiology and pathogenesis of periodontitis, and analyzes the bidirectional relationship between diabetes and periodontitis. In this review, we comprehensively summarize the four pathological microenvironments influenced by diabetic periodontitis: high glucose microenvironment, bacterial infection microenvironment, inflammatory microenvironment, and bone loss microenvironment. The hydrogel design strategies and latest research development tailored to the four microenvironments of diabetic periodontitis are mainly focused on. Finally, the challenges and potential solutions in the treatment of diabetic periodontitis are discussed. We believe this review will be helpful for researchers seeking novel avenues in the treatment of diabetic periodontitis.

6.
Biosens Bioelectron ; 262: 116539, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38950517

RESUMO

Prostaglandin E2 (PGE2), an eicosane, regulates the physiological activity of inflammatory cells and represents a potential therapeutic target for facilitating tissue repair in vivo. In our work, an electrochemical immunosensor employing Ketjen black-Au nanoparticles (KB-Au) and poly tannic acid nanospheres conjugated with anti-PGE2 polyclonal antibody (PTAN-Ab) was designed to ultra-sensitively analyze PGE2 levels secreted by living cells and tissues. Antibody assembly strategies were explored to achieve signal amplification. Moreover, we studied the therapy effects of docosahexaenoic acid (DHA), arachidonic acid (AA), hyaluronic acid (HA), and small molecule 15-hydroxyprostaglandin dehydrogenase inhibitor (SW033291) on inflammation and evaluated the protective functions of HA and SW033291 in a murine model subjected to colitis induced by dextran sulfate sodium (DSS) using the developed sensor. The sensor exhibited a linear range of 10-5-106 fg/mL and a detection limit (LOD) of 10-5 fg/mL. Fetal bovine serum (FBS) samples were used to achieve high recovery of target analytes. This study not only presents an effective strategy for ultra-sensitively monitoring PGE2 but also provides valuable insights into assessing the degree of inflammation and the therapeutic effect of related drugs. Research on human health monitoring and regenerative medicine could greatly benefit from the findings.

7.
J Pineal Res ; 76(5): e12989, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38978438

RESUMO

Colistin is renowned as a last-resort antibiotic due to the emergence of multidrug-resistant pathogens. However, its potential toxicity significantly hampers its clinical utilization. Melatonin, chemically known as N-acetyl-5-hydroxytryptamine, is an endogenous hormone produced by the pineal gland and possesses diverse biological functions. However, the protective role of melatonin in alleviating antibiotic-induced intestinal inflammation remains unknown. Herein, we reveal that colistin stimulation markedly elevates intestinal inflammatory levels and compromises the gut barrier. In contrast, pretreatment with melatonin safeguards mice against intestinal inflammation and mucosal damage. Microbial diversity analysis indicates that melatonin supplementation prevents a reduction in the abundance of Erysipelotrichales and Bifidobacteriales, as well as an increase in Desulfovibrionales abundance, following colistin exposure. Remarkably, short-chain fatty acids (SCFAs) analysis shows that propanoic acid contributes to the protective effect of melatonin on colistin-induced intestinal inflammation. Furthermore, the protection effects of melatonin and propanoic acid on LPS-induced cellular inflammation in RAW 264.7 cells are confirmed. Mechanistic investigations suggest that intervention with melatonin and propanoic acid can repress the activation of the TLR4 signal and its downstream NF-κB and MAPK signaling pathways, thereby mitigating the toxic effects of colistin. Our work highlights the unappreciated role of melatonin in preventing the potential detrimental effects of colistin on intestinal health and suggests a combined therapeutic strategy to effectively manage intestinal infectious diseases.


Assuntos
Colistina , Disbiose , Microbioma Gastrointestinal , Melatonina , Melatonina/farmacologia , Animais , Camundongos , Colistina/efeitos adversos , Disbiose/induzido quimicamente , Disbiose/metabolismo , Disbiose/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Células RAW 264.7 , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Inflamação/induzido quimicamente , Masculino , Antibacterianos/farmacologia , Camundongos Endogâmicos C57BL
8.
PeerJ ; 12: e17677, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974410

RESUMO

Background: The study aims to evaluate the diagnostic efficacy of contrast-enhanced ultrasound (CEUS) and shear-wave elastography (SWE) in detecting small malignant breast nodules in an effort to inform further refinements of the Breast Imaging Reporting and Data System (BI-RADS) classification system. Methods: This study retrospectively analyzed patients with breast nodules who underwent conventional ultrasound, CEUS, and SWE at Gongli Hospital from November 2015 to December 2019. The inclusion criteria were nodules ≤ 2 cm in diameter with pathological outcomes determined by biopsy, no prior treatments, and solid or predominantly solid nodules. The exclusion criteria included pregnancy or lactation and low-quality images. Imaging features were detailed and classified per BI-RADS. Diagnostic accuracy was assessed using receiver operating characteristic curves. Results: The study included 302 patients with 305 breast nodules, 113 of which were malignant. The diagnostic accuracy was significantly improved by combining the BI-RADS classification with CEUS and SWE. The combined approach yielded a sensitivity of 88.5%, specificity of 87.0%, positive predictive value of 80.0%, negative predictive value of 92.8%, and accuracy of 87.5% with an area under the curve of 0.877. Notably, 55.8% of BI-RADS 4A nodules were downgraded to BI-RADS 3 and confirmed as benign after pathological examination, suggesting the potential to avoid unnecessary biopsies. Conclusion: The integrated use of the BI-RADS classification, CEUS, and SWE enhances the accuracy of differentiating benign and malignant small breast nodule, potentially reducing the need for unnecessary biopsies.


Assuntos
Neoplasias da Mama , Meios de Contraste , Técnicas de Imagem por Elasticidade , Ultrassonografia Mamária , Humanos , Feminino , Técnicas de Imagem por Elasticidade/métodos , Estudos Retrospectivos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Adulto , Ultrassonografia Mamária/métodos , Idoso , Sensibilidade e Especificidade , Curva ROC , Mama/diagnóstico por imagem , Mama/patologia
9.
Virol J ; 21(1): 155, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982509

RESUMO

BACKGROUND: Canine enteric coronavirus (CECoV) is a prevalent infectious disease among dogs worldwide, yet its epidemiology in mainland China remains poorly understood. This systematic review and meta-analysis aimed to assess the prevalence of CECoV in mainland China and identify factors influencing its prevalence. METHODS: A comprehensive literature search was conducted across multiple databases for studies regarding CECoV epidemiology of China. PubMed, CNKI, Wanfang, and CQVIP were searched to obtain the studies. Eligible studies were selected based on predefined criteria, and data were extracted and synthesized. The quality the studies was assessed using the JBI assessment tool. Heterogeneity was checked using I2 test statistics followed by subgroup and sensitivity analysis. Subgroup analyses were performed to explore variations in CECoV prevalence by factors such as year, region, season, health status, social housing type, gender, age, and breed. Publication bias was assessed using a funnel plot and eggers test that was followed by trim and fill analysis. RESULTS: A total of 27 studies involving 21,034 samples were included in the meta-analysis. The overall pooled prevalence of CECoV in mainland China was estimated to be 0.30 (95% CI 0.24-0.37), indicating persistent circulation of the virus. Subgroup analyses revealed higher prevalence rates in younger dogs, multi-dog households, apparently healthy dogs, and certain regions such as southwest China. Seasonal variations were observed, with lower prevalence rates in summer. However, no significant differences in prevalence were found by gender. CONCLUSIONS: This study provides valuable insights into the epidemiology of CECoV in mainland China, highlighting the persistent circulation of the virus and identifying factors associated with higher prevalence rates. Continuous monitoring and surveillance efforts, along with research into accurate detection methods and preventive measures, are essential for the effective control of CECoV and mitigation of its potential impact on animal and human health.


Assuntos
Infecções por Coronavirus , Coronavirus Canino , Doenças do Cão , Animais , Cães , China/epidemiologia , Prevalência , Doenças do Cão/epidemiologia , Doenças do Cão/virologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Coronavirus Canino/genética , Coronavirus Canino/isolamento & purificação
10.
Complement Ther Clin Pract ; 57: 101877, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38996656

RESUMO

BACKGROUND AND PURPOSE: Electroacupuncture (EA) is one of the non-pharmacological therapies in traditional Chinese medicine to treat urinary retention. The objective of this meta-analysis is to assess the efficacy of electroacupuncture in the treatment of urinary retention after stroke. METHODS: Overall, seven electronic databases were searched until December 31, 2023, and randomized control trials about EA for urinary retention after stroke were reviewed. Two reviewers independently screened the literature, extracted the data, and assessed the risk of bias for included studies. The meta-analysis was conducted by RevMan 5.4 and Stata/MP 17.0 software. RESULTS: Eleven studies with a total of 856 participants were included in this meta-analysis. EA treatment yielded an improved reduction in the post-void residual (PVR) (mean difference [MD]: 37.85, 95 % confidence interval [CI]: 55.09 to -20.61 p < 0.0001) and the weight of diaper pads (MD: 38.87, 95 % CI: 42.68 to -335.06). Further analysis indicated that EA improved the effectiveness ratio (risk ratio [RR]: 1.36, 95 % CI: 1.20 to 1.53, p < 0.00001), the function of the bladder (MD: 0.45, 95 % CI: 0.61 to -0.30), and the quality of life (MD: 1.15, 95 %: CI: 2.10 to -0.20) in comparison to normal treatment and simple acupuncture. CONCLUSION: EA may be an effective way and reasonable modality to incorporate into the multiple prevention and therapy for urinary retention after stroke. The wide application of EA could be associated with the improvement of bladder and life quality and decline in the PVR for patients after stroke with urinary retention.

11.
Endocr Metab Immune Disord Drug Targets ; : e060324227740, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38988067

RESUMO

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a highly prevalent, complex, heterogeneous, polygenic endocrine disorder characterized by metabolic and reproductive dysfunction that affects 8-13% of women of reproductive age worldwide. The pathogenesis of PCOS has not been fully clarified and includes genetics, obesity, and insulin resistance (IR). Oxidative stress (OS) of PCOS is independent of obesity. It can induce IR through post-insulin receptor defects, impair glucose uptake in muscle and adipose tissue, and exacerbate IR by reducing insulin secretion from pancreatic ß-cells. OBJECTIVE: To investigate the effects of Calorie Restricted Diet (CRD), High Protein Diet (HPD), and High Protein and High Dietary Fiber Diet (HPD+HDF) on body composition, insulin resistance, and oxidative stress in overweight/obese PCOS patients. METHODS: A total of 90 overweight/obese patients with PCOS were selected to receive an 8- week medical nutrition weight loss intervention at our First Hospital of Peking University, and we randomly divided them into the CRD group (group A), the HPD group (group B), and the HPD+HDF group (group C), with 30 patients in each group. We measured their body composition, HOMA-IR index, and oxidative stress indicators. The t-test, Mann-Whitney U test, analysis of variance (ANOVA), and Kruskal-Wallis H test were used to compare the efficacy of the three methods. RESULTS: After eight weeks, the body weights of the three groups decreased by 6.32%, 5.70% and 7.24%, respectively, and the Visceral Fat Area (VFA) values decreased by 6.8 cm2, 13.4 cm2 and 23.45 cm2, respectively, especially in group C (p >0.05). The lean body mass (LBM), also known as the Fat-Free Mass (FFM) values of group B and group C after weight loss, were higher than that of group A (p >0.05). After weight loss, the homeostatic model assessment of insulin resistance (HOMA-IR) index and malondialdehyde (MDA) were decreased. Superoxide dismutase (SOD) was increased in all three groups (p >0.05), and the changes in SOD and MDA in group B and group C were more significant (p >0.05). HOMA-IR index positively correlated with body mass index (BMI) (r=0.195; p >0.05); MDA positively correlated with percent of body fat (PBF) (r=0.186; p >0.05) and HOMA-IR index (r=0.422; p >0.01); SOD positively correlated with LMI/FFMI (r=0.195; p >0.05), negatively correlated with HOMA-IR index (r=-0.433; p >0.01). CONCLUSION: All three diets were effective in reducing the body weight of overweight/obese patients with PCOS by more than 5% within 8 weeks and could improve both insulin resistance and oxidative stress damage. Compared with CRD, HPD and HPD+HDF diets could better retain lean body mass and significantly improve oxidative stress damage. CLINICAL TRIAL NUMBER: ChiCTR2100054961.

12.
Artigo em Inglês | MEDLINE | ID: mdl-39010832

RESUMO

Irritable bowel syndrome with diarrhea (IBS-D) is a common intestinal condition that significantly impacts work efficiency and quality of life. The use of animal models is crucial for delving into the pathophysiology of IBS-D and exploring therapeutic options. However, a wide variety of animal models for IBS-D has been employed in previous studies, posing a considerable challenge for researchers in selecting a suitable model. In this review, conducted using the Web of Science database, we searched IBS-D-related research spanning from 2014 to 2023, described the differences in animal strains and modeling methods among various IBS-D features recapitulating models, summarized the frequency of model usage, pathogenesis, and pathological characteristics of these models, and discussed their current applications, limitations, and future perspectives. The objective is to offer theoretical guidance for future researchers, aiding them in choosing suitable animal models based on their experimental designs.

13.
Front Microbiol ; 15: 1340429, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38881663

RESUMO

Calcium (Ca2+) can regulate the swarming motility and virulence of Vibrio parahaemolyticus BB22. However, the effects of Ca2+ on the physiology of V. parahaemolyticus RIMD2210633, whose genomic composition is quite different with that of BB22, have not been investigated. In this study, the results of phenotypic assays showed that the biofilm formation, c-di-GMP production, swimming motility, zebrafish survival rate, cytoxicity against HeLa cells, and adherence activity to HeLa cells of V. parahaemolyticus RIMD2210633 were significantly enhanced by Ca2+. However, Ca2+ had no effect on the growth, swarming motility, capsular polysaccharide (CPS) phase variation and hemolytic activity. The RNA sequencing (RNA-seq) assay disclosed 459 significantly differentially expressed genes (DEGs) in response to Ca2+, including biofilm formation-associated genes and those encode virulence factors and putative regulators. DEGs involved in polar flagellum and T3SS1 were upregulated, whereas majority of those involved in regulatory functions and c-di-GMP metabolism were downregulated. The work helps us understand how Ca2+ affects the behavior and gene expression of V. parahaemolyticus RIMD2210633.

14.
Front Pharmacol ; 15: 1387409, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38887546

RESUMO

Our previous study highlighted the therapeutic potential of glutathione (GSH), an intracellular thiol tripeptide ubiquitous in mammalian tissues, in mitigating hepatic and cerebral damage. Building on this premise, we posited the hypothesis that GSH could be a promising candidate for treating acute hepatic encephalopathy (AHE). To verify this conjecture, we systematically investigated the feasibility of GSH as a therapeutic agent for AHE through comprehensive pharmacokinetic, pharmacodynamic, and mechanistic studies using a thioacetamide-induced AHE rat model. Our pharmacodynamic data demonstrated that oral GSH could significantly improve behavioral scores and reduce hepatic damage of AHE rats by regulating intrahepatic ALT, AST, inflammatory factors, and homeostasis of amino acids. Additionally, oral GSH demonstrated neuroprotective effects by alleviating the accumulation of intracerebral glutamine, down-regulating glutamine synthetase, and reducing taurine exposure. Pharmacokinetic studies suggested that AHE modeling led to significant decrease in hepatic and cerebral exposure of GSH and cysteine. However, oral GSH greatly enhanced the intrahepatic and intracortical GSH and CYS in AHE rats. Given the pivotal roles of CYS and GSH in maintaining redox homeostasis, we investigated the interplay between oxidative stress and pathogenesis/treatment of AHE. Our data revealed that GSH administration significantly relieved oxidative stress levels caused by AHE modeling via down-regulating the expression of NADPH oxidase 4 (NOX4) and NF-κB P65. Importantly, our findings further suggested that GSH administration significantly regulated the excessive endoplasmic reticulum (ER) stress caused by AHE modeling through the iNOS/ATF4/Ddit3 pathway. In summary, our study uncovered that exogenous GSH could stabilize intracerebral GSH and CYS levels to act on brain oxidative and ER stress, which have great significance for revealing the therapeutic effect of GSH on AHE and promoting its further development and clinical application.

15.
J Antibiot (Tokyo) ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898184

RESUMO

The development of new therapeutic uses for existing drugs is important for the treatment of some diseases. Cephalosporin antibiotics stand as the most extensively utilized antibiotics in clinical practice, effectively combating bacterial infections. Here, we found that the antimicrobial drug ceftazidime strongly upregulates p27 protein levels by inhibiting p27 ubiquitination. The p27 protein is a classic negative regulator of the cell cycle. Next, we demonstrated that ceftazidime can impede the cell cycle from G1 to S phase, thus inhibiting cell proliferation. Furthermore, we found that ceftazidime promotes p27 expression and inhibits cell proliferation by reducing Skp2, which is a substrate recognition component of the Skp2-Cullin-F-box (SCF) ubiquitin ligase. Moreover, ceftazidime downregulates transcriptional expression of Skp2. Importantly, we demonstrated that ceftazidime inhibited the proliferation of tumor cells in vivo. These findings reveal ceftazidime-mediated inhibition of cell proliferation through the Skp2-p27 axis, and could provide a potential strategy for anti-tumor therapy.

16.
Oncogene ; 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879588

RESUMO

Humans are widely exposed to phthalates, a major chemical plasticizer that accumulates in the liver. However, little is known about the impact of chronic phthalate exposure on liver cancer development. In this study, we applied a long-term cell culture model by treating the liver cancer cell HepG2 and normal hepatocyte L02 to environmental dosage of monobutyl phthalate (MBP), the main metabolite of phthalates. Interestingly, we found that long-term MBP exposure significantly accelerated the growth of HepG2 cells in vitro and in vivo, but barely altered the function of L02 cells. MBP exposure triggered reprogramming of lipid metabolism in HepG2 cells, where cholesterol accumulation subsequently activated the IRE1α-XBP1s axis of the unfolded protein response. As a result, the XBP1s-regulated gene sets and pathways contributed to the increased aggressiveness of HepG2 cells. In addition, we also showed that MBP-induced cholesterol accumulation fostered an immunosuppressive microenvironment by promoting tumor-associated macrophage polarization toward the M2 type. Together, these results suggest that environmental phthalates exposure may facilitate liver cancer progression, and alerts phthalates exposure to patients who already harbor liver tumors.

17.
Ren Fail ; 46(2): 2365396, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38874150

RESUMO

OBJECTIVE: The aim of this study was to investigate the potential importance of complement system activation, with particular emphasis on the complement alternative pathway (AP), in the pathogenesis of hypertensive renal damage. METHODS: Serum complement C3, complement Factor H (CFH) and AP activation were assessed in 66 participants with established essential hypertension with renal damage (RD). Fifty-nine patients with age- and sex-matched essential hypertension without renal damage (NRD) and 58 healthy participants (normal) were selected. RESULTS: Our study revealed that C3 and AP50 continuously increased from normal to NRD to RD (p < 0.05, respectively), while CFH was significantly lower than that in NRD and healthy participants (p < 0.05, respectively). After multifactorial logistic regression analysis corrected for confounders, elevated serum C3 (p = 0.001) and decreased CFH (p < 0.001) were found to be independent risk factors for hypertension in healthy participants; elevated serum C3 (p = 0.034), elevated AP50 (p < 0.001), decreased CFH (p < 0.001), increased age (p = 0.011) and increased BMI (p = 0.013) were found to be independent risk factors for the progression of hypertension to hypertensive renal damage; elevated serum C3 (p = 0.017), elevated AP50 (p = 0.023), decreased CFH (p = 0.005) and increased age (p = 0.041) were found to be independent risk factors for the development of hypertensive renal damage in healthy participants. CONCLUSION: Abnormal activation of complement, particularly complement AP, may be a risk factor for the development and progression of hypertensive renal damage.


Assuntos
Complemento C3 , Fator H do Complemento , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Complemento C3/metabolismo , Complemento C3/análise , Fatores de Risco , Idoso , Adulto , Hipertensão/complicações , Hipertensão/sangue , Ativação do Complemento , Hipertensão Essencial/sangue , Hipertensão Essencial/complicações , Hipertensão Essencial/fisiopatologia , Modelos Logísticos , Via Alternativa do Complemento , Progressão da Doença
18.
Heliyon ; 10(11): e32478, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38933978

RESUMO

Vertebrate testosterone, an androgen present in the testes, is essential for male fertility. Vertebrate-type steroid hormones have been identified in insects, but their function remains unknown. Insect vitellogenin (Vg) is usually a female-specific protein involved in reproductive processes. However, males of some species, such as the green lacewing Chrysopa pallens, have Vg. Here, we demonstrated that the knockdown of C. pallens male Vg by RNAi significantly shortened the lifespan of males, suppressed the reproduction of post-mating females, and strikingly reduced the abundance of several immune-related compounds, including testosterone. LC-MS/MS revealed that C. pallens male testosterone had the same structure and molecular mass as vertebrate testosterone. Topical testosterone application partially restored the lifespan of Vg-deficient males and the reproduction of post-mating females. These results suggest that vertebrate-type testosterone maintains male longevity and female reproduction under the control of the male Vg in C. pallens.

20.
Genomics ; 116(5): 110890, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38909906

RESUMO

Previous studies have presented evidence suggesting that altitude exerts detrimental effects on reproductive processes, yet the underlying mechanism remains elusive. Our study employed two distinct goat breeds inhabiting low and high altitudes, and conducted a comparative analysis of mRNA profiles in testis tissues and the composition of gut microbiota. The results revealed a reduced testis size in high-altitude goats. RNA-seq analysis identified the presence of 214 differentially expressed genes (DEGs) in the testis. These DEGs resulted in a weakened immunosuppressive effect, ultimately impairing spermatogenesis in high-altitude goats. Additionally, 16S rDNA amplicon sequencing recognized statistically significant variations in the abundance of the genera Treponema, unidentified_Oscillospiraceae, Desulfovibrio, Butyricicoccus, Dorea, Parabacteroides between the two groups. The collective evidence demonstrated the gut and testis played a synergistic role in causing decreased fertility at high altitudes. Our research provides a theoretical basis for future investigations into the reproductive fitness of male goats.

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