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1.
Cytokine ; 173: 156446, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37979213

RESUMO

OBJECTIVES: Previous studies have reported an association between inflammatory cytokines and inflammatory arthritis, including Ankylosing spondylitis (AS), rheumatoid arthritis (RA), and psoriatic arthritis (PsA). This study aims to explore the causal relationship between inflammatory cytokines and AS, RA, and PsA using Mendelian randomization (MR). METHODS: We conducted a bidirectional two-sample MR analysis using genetic summary data from a publicly available genome-wide association study (GWAS) that included 41 genetic variations of inflammatory cytokines, as well as genetic variant data for AS, RA, and PsA from the FinnGen consortium. The main analysis method used was Inverse variance weighted (IVW) to investigate the causal relationship between exposure and outcome. Additionally, other methods such as MR Egger, weighted median (WM), simple mode, and weighted mode were employed to strengthen the final results. Sensitivity analysis was also performed to ensure the reliability of the findings. RESULTS: The results showed that macrophage colony-stimulating factor (MCSF) was associated with an increased risk of AS (OR = 1.163, 95 % CI = 1.016-1.33, p = 0.028). Conversely, high levels of TRAIL and beta nerve growth factor (ß-NGF) were associated with a decreased risk of AS (OR = 0.892, 95 % CI = 0.81-0.982, p = 0.002; OR = 0.829, 95 % CI = 0.696-0.988, p = 0.036). Four inflammatory cytokines were found to be associated with an increased risk of PsA: vascular endothelial growth factor (VEGF) (OR = 1.161, 95 % CI = 1.057-1.275, p = 0.002); Interleukin 12p70 (IL12p70) (OR = 1.189, 95 % CI = 1.049-1.346, p = 0.007); IL10 (OR = 1.216, 95 % CI = 1.024-1.444, p = 0.026); IL13 (OR = 1.159, 95 % CI = 1.05-1.28, p = 0.004). Interleukin 1 receptor antagonist (IL-1rα) was associated with an increased risk of seropositive RA (OR = 1.181, 95 % CI = 1.044-1.336, p = 0.008). Similarly, genetic susceptibility to inflammatory arthritis was found to be causally associated with multiple inflammatory cytokines. Lastly, the sensitivity analysis supported the robustness of these findings. CONCLUSIONS: This study provides additional insights into the relationship between inflammatory cytokines and inflammatory arthritis, and may offer new clues for the etiology, diagnosis, and treatment of inflammatory arthritis.


Assuntos
Artrite Psoriásica , Artrite Reumatoide , Espondilite Anquilosante , Humanos , Citocinas/genética , Artrite Psoriásica/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Reprodutibilidade dos Testes , Fator A de Crescimento do Endotélio Vascular , Artrite Reumatoide/genética , Espondilite Anquilosante/genética
2.
J Org Chem ; 89(11): 8064-8075, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38757807

RESUMO

Reported herein is the 1,2-dithiocyanation of alkenes and alkynes via an efficient and facile electrochemical method. This approach not only showed a broad substrate scope and good functional-group compatibility but also avoided stoichiometric oxidants. Different from previous reports, various internal alkynes could be tolerated to provide tetra-substituted alkenes. Further gram-scale-up experiments and synthetic transformation demonstrated a potential application in organic synthesis. This process underwent a radical pathway, as evidenced by our mechanistic studies.

3.
J Org Chem ; 89(8): 5783-5796, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38591967

RESUMO

A visible-light-induced radical-cascade selenocyanation/cyclization of N-alkyl-N-methacryloyl benzamides, 2-aryl-N-acryloyl indoles, and N-methacryloyl-2-phenylbenzimidazoles with potassium isoselenocyanate (KSeCN) was developed. The reactions were carried out with inexpensive KSeCN as a selenocyanation reagent, potassium persulfate as an oxidant, 2,4,6-triphenylpyrylium tetrafluoroborate as a bifunctional catalyst for phase-transfer catalysis, and photocatalysis. A library of selenocyanate-containing isoquinoline-1,3(2H,4H)-diones, indolo[2,1-a]isoquinoline-6(5H)-ones, and benzimidazo[2,1-a]isoquinolin-6(5H)-ones were achieved in moderate to excellent yields at room temperature under visible-light and ambient conditions. Importantly, the present protocol features mild reaction conditions, large-scale synthesis, simple manipulation, product derivatization, good functional group, and heterocycle tolerance.

4.
Environ Toxicol ; 39(1): 264-276, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37705229

RESUMO

Co-existing of polystyrene-nano plastics (PSNPs) and arsenic (As) in the environment caused a horrendous risk to human health. However, the potential mechanism of PSNPs and As combination induced testicular toxicity in mammals has not been elucidated. Therefore, we first explore the testicular toxicity and the potential mechanism in male Kunming mice exposed to As or/and PSNPs. Results revealed that compared to the As or PSNPs group, the combined group showed more significant testicular toxicity. Specifically, As and PSNPs combination induced irregular spermatozoa array and blood-testis barrier disruption. Simultaneously, As and PSNPs co-exposure also exacerbated oxidative stress, including increasing the MDA content, and down-regulating expression of Nrf-2, HO-1, SOD-1, and Trx. PSNPs and As combination also triggered testicular apoptosis, containing changes in apoptotic factors (P53, Bax, Bcl-2, Cytc, Caspase-8, Caspase-9, and Caspase-3). Furthermore, co-exposed to As and PSNPs aggravated inflammatory damage characterized by targeted phosphorylation of NF-κB and degradation of I-κB. In summary, our results strongly confirmed As + PSNPs co-exposure induced the synergistic toxicity of testis through excessive oxidative stress, apoptosis, and inflammation, which could offer a new sight into the mechanism of environmental pollutants co-exposure induced male reproductive toxicity.


Assuntos
Arsênio , Testículo , Camundongos , Humanos , Masculino , Animais , Testículo/metabolismo , Poliestirenos/toxicidade , Arsênio/toxicidade , Arsênio/metabolismo , Microplásticos , Plásticos/metabolismo , Estresse Oxidativo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Apoptose , Mamíferos/metabolismo
5.
BMC Immunol ; 24(1): 32, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37752439

RESUMO

BACKGROUND: HLA-B27 positivity is normal in patients undergoing rheumatic diseases. The diagnosis of many diseases requires an HLA-B27 examination. METHODS: This study screened totally 1503 patients who underwent HLA-B27 examination, liver/kidney function tests, and complete blood routine examination in First Affiliated Hospital of Guangxi Medical University. The training cohort included 509 cases with HLA-B27 positivity whereas 611 with HLA-B27 negativity. In addition, validation cohort included 147 cases with HLA-B27 positivity whereas 236 with HLA-B27 negativity. In this study, 3 ML approaches, namely, LASSO, support vector machine (SVM) recursive feature elimination and random forest, were adopted for screening feature variables. Subsequently, to acquire the prediction model, the intersection was selected. Finally, differences among 148 cases with HLA-B27 positivity and negativity suffering from ankylosing spondylitis (AS) were investigated. RESULTS: Six factors, namely red blood cell count, human major compatibility complex, mean platelet volume, albumin/globulin ratio (ALB/GLB), prealbumin, and bicarbonate radical, were chosen with the aim of constructing the diagnostic nomogram using ML methods. For training queue, nomogram curve exhibited the value of area under the curve (AUC) of 0.8254496, and C-value of the model was 0.825. Moreover, nomogram C-value of the validation queue was 0.853, and the AUC value was 0.852675. Furthermore, a significant decrease in the ALB/GLB was noted among cases with HLA-B27 positivity and AS cases. CONCLUSION: To conclude, the proposed ML model can effectively predict HLA-B27 and help doctors in the diagnosis of various immune diseases.


Assuntos
Antígeno HLA-B27 , Nomogramas , Humanos , Antígeno HLA-B27/genética , China , Fígado , Aprendizado de Máquina
6.
J Org Chem ; 88(20): 14649-14658, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37816698

RESUMO

A metal-free and selective oxidative methyl C-H functionalization of BHT with aniline compounds has been developed. This innovative method enables the facile and efficient synthesis of a diverse array of BHT-functionalized N-containing skeletons, including arylamines, benzoxazoles, benzothiazoles, benzimidazoles, quinazolines, and quinazolinones, all of which are challenging to access. The control experiment involving TEMP18O suggests that the radical adduct of TEMPO with the benzyl radical of BHT may serve as an intermediate.

7.
BMC Surg ; 23(1): 63, 2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-36959639

RESUMO

BACKGROUND: In the elderly, osteoporotic vertebral compression fractures (OVCFs) of the thoracolumbar vertebra are common, and percutaneous vertebroplasty (PVP) is a common surgical method after fracture. Machine learning (ML) was used in this study to assist clinicians in preventing bone cement leakage during PVP surgery. METHODS: The clinical data of 374 patients with thoracolumbar OVCFs who underwent single-level PVP at The First People's Hospital of Chenzhou were chosen. It included 150 patients with bone cement leakage and 224 patients without it. We screened the feature variables using four ML methods and used the intersection to generate the prediction model. In addition, predictive models were used in the validation cohort. RESULTS: The ML method was used to select five factors to create a Nomogram diagnostic model. The nomogram model's AUC was 0.646667, and its C value was 0.647. The calibration curves revealed a consistent relationship between nomogram predictions and actual probabilities. In 91 randomized samples, the AUC of this nomogram model was 0.7555116. CONCLUSION: In this study, we invented a prediction model for bone cement leakage in single-segment PVP surgery, which can help doctors in performing better surgery with reduced risk.


Assuntos
Fraturas por Compressão , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Vertebroplastia , Humanos , Idoso , Cimentos Ósseos , Fraturas por Compressão/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Vertebroplastia/métodos , Fraturas por Osteoporose/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
8.
Toxicol Appl Pharmacol ; 434: 115820, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34896432

RESUMO

Arsenic is a well-known environmental pollutant due to its toxicity, which can do harm to animals and human. Curcumin is a polyphenolic compound derived from turmeric, commonly accepted to have antioxidant properties. However, whether curcumin can ameliorate the damage caused by arsenic trioxide (ATO) in duck skeletal muscle remains largely unknown. Therefore, the present study aims to investigate the potential molecular mechanism of curcumin against ATO-induced skeletal muscle injury. The results showed that treating with curcumin could attenuate body weight loss induced by ATO and reduced arsenic content accumulation in the skeletal muscle of duck. Curcumin was also able to alleviated the oxidative stress triggered by ATO, which was manifested by the increase of T-AOC and SOD, and MDA decrease. Moreover, we observed that curcumin could ease mitochondrial damage and vacuolate degeneration of nucleus. Our further investigation found that ATO disrupted normal mitochondrial fission/fusion (Drp1, OPA1, Mfn1/2) and restrained mitochondrial biogenesis (PGC-1α, Nrf1/2, TFAM), while curcumin could promote mitochondrial fusion and activated PGC-1α pathway. Furthermore, curcumin was found that it could not only reduce the mRNA and protein levels of mitophagy (PINK1, Parkin, LC3, p62) and pro-apoptotic genes (p53, Bax, Caspase-3, Cytc), but also increased the levels of anti-apoptotic genes (Bcl-2). In conclusion, curcumin was able to alleviate ATO-induced skeletal muscle damage by improving mitophagy and preserving mitochondrial function, which can serve as a novel strategy to take precautions against ATO toxicity.


Assuntos
Arsênio/toxicidade , Curcumina/uso terapêutico , Mitocôndrias/efeitos dos fármacos , Doenças Musculares/induzido quimicamente , Proteínas Quinases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Biologia Computacional , Patos , Poluentes Ambientais/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitofagia/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Proteínas Quinases/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ubiquitina-Proteína Ligases/genética
9.
J Org Chem ; 87(14): 9112-9127, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35786919

RESUMO

The ubiquity of benzoxazoles in natural products, drugs, and functional materials has stimulated numerous efforts toward their synthesis; however, the developed methods rely on prefunctionalized substrates and lack generality. Under metal-free conditions, a highly general synthesis of benzoxazoles direct from abundant and easily available phenols and amines is developed via a modular phenol functionalization controlled by TEMPO. In the reaction, various phenols and primary amines with a broad range of functional groups are compatible, producing structurally and functionally diverse benzoxazoles (64 examples) without or with trace observation of the byproducts of phenol transformation with amines. The practical synthesis, especially for drug tafamidis, demonstrates decisive advantages in generality, selectivity, efficiency, and atom- and step-economies over traditional methods, even in the cases of low yields. Mechanistically, the radical adducts of TEMPO with ortho-cyclohexa-2,4-dien-1-one radicals rather than the well-recognized cyclohexa-3,5-diene-1,2-diones may serve as intermediates.


Assuntos
Aminas , Fenóis , Benzoxazóis , Catálise , Metais , Estresse Oxidativo , Fenol
10.
Org Biomol Chem ; 20(27): 5416-5422, 2022 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-35748805

RESUMO

A facile synthesis of 1H-imidazoles by direct oxidative annulation of aryl methyl ketones and primary amines has been developed in the presence of TEMPO under weakly acidic conditions. By replacing amines with ammonium acetate, 2H-imidazole skeletons were achieved for the first time from ketones. Substrates containing various functional groups, such as alkyl, aryl, naphthyl, halogen (F, Cl, Br, I), nitro, trifluoromethyl, sulfonyl ester, furyl, thienyl, and pyridyl groups, were readily transformed into the desired products. The application potential of this method was verified by the scale-up synthesis and Sonogashira coupling functionalization of imidazoles. Mechanistically, the α-TEMPO-enamine adduct may serve as the key reaction intermediate.


Assuntos
Aminas , Cetonas , Acetatos , Acetona , Catálise , Óxidos N-Cíclicos , Imidazóis , Estresse Oxidativo
11.
J Clin Lab Anal ; 36(3): e24256, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35089616

RESUMO

BACKGROUND: The study aimed to analyze the clinical effects of pulmonary embolism succeeding a third surgery conducted for multiple recurrences in thoracic tuberculosis (TB). CASE REPORT: A 74-year-old female patient developed thoracic tuberculosis and was subsequently treated in our hospital in March 2019, October 2020, and February 2021. The third surgical intervention included anterolateral thoracic lesion resection, internal fixation, posterior spinal tuberculous sinus resection, and debridement with suture. The operative time was 172 min resulting in a substantial intraoperative blood loss (2321 ml). Postoperative re-examination of chest CTPA indicated a strip filling defect and pulmonary embolism in the external branch of the right middle lobe of the lung. After completing the active treatment, the D-dimer quantification, WBC, CRP, and ESR values were 1261 ng/ml, 7.71 × 109 /L, 74.66 mg/L, and 63 mm, respectively. Chest CTPA re-examination after the treatment showed no signs of pulmonary embolism. CONCLUSION: Patients with a long-term history of multiple operations, high BMI, cerebral infarction, diabetes, and older age group were more likely to develop pulmonary embolism after spinal tuberculosis surgery. Thus, the possibility of postoperative pulmonary embolism should be thoroughly analyzed before any subsequent surgical treatment in patients with recurrent spinal tuberculosis.


Assuntos
Embolia Pulmonar , Fusão Vertebral , Tuberculose da Coluna Vertebral , Idoso , Desbridamento/métodos , Feminino , Humanos , Vértebras Lombares/cirurgia , Embolia Pulmonar/etiologia , Embolia Pulmonar/cirurgia , Estudos Retrospectivos , Fusão Vertebral/métodos , Vértebras Torácicas/cirurgia , Resultado do Tratamento
12.
BMC Musculoskelet Disord ; 23(1): 182, 2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35216570

RESUMO

OBJECTIVE: The present study attempted to predict blood transfusion risk in spinal tuberculosis surgery by using a novel predictive nomogram. METHODS: The study was conducted on the clinical data of 495 patients (167 patients in the transfusion group and 328 patients in the non-transfusion group) who underwent spinal tuberculosis surgery in our hospital from June 2012 to June 2021. The least absolute shrinkage and selection operator (LASSO) and multivariable logistic regression analyses were used to screen out statistically significant parameters, which were included to establish a novel predictive nomogram model. The receiver operating characteristic (ROC) curve, calibration curves, C-index, and decision curve analysis (DCA) were used to evaluate the model. Finally, the nomogram was further assessed through internal validation. RESULTS: The C-index of the nomogram was 0.787 (95% confidence interval: 74.6%-.82.8%). The C-value calculated by internal validation was 0.763. The area under the curve (AUC) of the predictive nomogram was 0.785, and the DCA was 0.01-0.79. CONCLUSION: A nomogram with high accuracy, clinical validity, and reliability was established to predict blood transfusion risk in spinal tuberculosis surgery. Surgeons must prepare preoperative surgical strategies and ensure adequate availability of blood before surgery.


Assuntos
Nomogramas , Tuberculose da Coluna Vertebral , Transfusão de Sangue , Humanos , Reprodutibilidade dos Testes , Fatores de Risco , Tuberculose da Coluna Vertebral/diagnóstico , Tuberculose da Coluna Vertebral/cirurgia
13.
Ecotoxicol Environ Saf ; 230: 113117, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34959015

RESUMO

Arsenic is a dangerous metalloid-material which is known to cause liver injury in many animals and humans. However, little is known about the underlying mechanism of arsenic-induced hepatotoxicity in poultry. This study was executed to systematically investigate the potential role of mitochondrial biogenesis, mitophagy and apoptosis in duck hepatotoxicity caused by arsenic. Results showed that the body weight and liver coefficient of duck had distinct changed after arsenic-exposure, and the arsenic content in serum and liver also increased significantly in a dose-dependent manner. Meanwhile, histopathological examination and metabolomics results showed that arsenic-exposure caused severe steatosis and metabolism disorder in liver tissues. Furthermore, arsenic-exposure significantly inhibited AMPK/PGC-1α-mediated mitochondrial biogenesis, determined by the ultrastructure observation and down-regulation of p-AMPKα/AMPKα, PGC-1α, NRF1, NRF2, TFAM, TFB1M, TFB2M and COX-Ⅳ expression levels. Besides, arsenic-treatment obviously increased the levels of mitophagy (PINK1, Parkin, LC3, P62) and pro-apoptotic (Caspase-3, Caspase-9, Cleaved Caspase-3, Cytc, Bax, P53) indexes, and simultaneously resulted in reductions in anti-apoptosis index (Bcl-2). Overall, our findings provided evidences that arsenic-induced duck hepatotoxicity may be caused by a combination of impaired mitochondrial biosynthesis, mitophagy, and mitochondrial-dependent apoptosis. To our knowledge, this is the first report to systematically investigate the potential mechanism of arsenic-induced hepatotoxicity in poultry.

14.
BMC Surg ; 22(1): 334, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36085145

RESUMO

BACKGROUND: Laparoscopic-assisted repairs for pediatric inguinal hernia have gained gradual acceptance over the past decade. However, consensus about the optimal management is still lacking. The aim of this study is to compare outcomes of a modified laparoscope-assisted single-needle laparoscopic percutaneous extraperitoneal closure (LPEC) versus open repair of pediatric hernias/hydrocele in a single institution. MATERIALS AND METHODS: We retrospectively reviewed the medical data of children who underwent laparoscope-assisted single-needle LPEC and open repair (OR) for inguinal hernia from 2014 to 2019. Data collection included demographics, laterality of hernia, surgical time and time to follow-up. We also reviewed and analyzed the evidence of recurrence, the incidence of metachronous contralateral inguinal hernia (MCIH), and other complications. RESULTS: In our cohort, 961 patients in the OR group and 1098 patients in the LPEC group were analyzed retrospectively. Mean operative time was significantly shorter in the LPEC group (22.3 ± 3.5 min) than in the OR group (27.8 ± 5.9 min) for bilateral hernia repair (p < 0.001). Postoperative recurrence was 1.3% (13/1035) in the OR group and 0.5% (6/1182) in the LPEC group (p = 0.056). Iatrogenic cryptorchidism occurred statistically more frequently in the OR group than in the LPEC group (0.4% vs. 0%, p = 0.013). In addition, the incidence of MCIH was 3.7% (33/887) in the OR group and 0.3% (3/1014) in the LPEC group (p < 0.01). CONCLUSION: Comparing to open technique, laparoscope-assisted single-needle LPEC provides a simple and effective option for pediatric inguinal hernia/hydrocele repair with excellent outcomes, a low incidence of recurrence, and reduced MCIH.


Assuntos
Hérnia Inguinal , Laparoscopia , Hidrocele Testicular , Criança , Hérnia Inguinal/cirurgia , Humanos , Laparoscópios , Masculino , Agulhas , Estudos Retrospectivos
15.
Ecotoxicol Environ Saf ; 228: 112965, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34775344

RESUMO

Arsenic trioxide (ATO) has confirmed as a global pollutant, the toxic effect of which was not fully understood and lack effective therapies to against its associated toxicities. Curcumin (Cur) is a beneficial natural pigment for its antioxidant and anti-inflammatory properties. The purpose of this paper was to illustrate the antagonism of Cur against ATO-induced neurotoxicity. A total of 40 ducks were divided randomly into 4 groups and conducted via bite and sup for 28 days: control group (Control); 2 mg/kg ATO group (Low ATO); 4 mg/kg ATO group (Middle ATO); 8 mg/kg ATO group (High ATO); 400 mg/kg Cur group + 8 mg/kg ATO (Cur+ATO). The results showed that ATO exposure can hinder the duck growth and arsenic element accumulation rate increased in a dose-dependent manner. We observed neuronal shrinkage and vacuolize of HE staining in the ATO-treated group. In addition, SOD activity and T-AOC level reduced while MDA content increased in the ATO-exposed group. ATO exposure can decrease the expression of anti-oxidation related mRNA and proteins (Nrf2, SOD-1, GPX-1, CAT, Trx and HO-1) and anti-inflammatory makers (IL-4, IL-10), increased the expression of Keap1, NF-κB and pro-inflammatory makers (TNF-α, IL-1ß, IL-18, IL-2, IL-6, INOS and COX-2). ATO treated might cause blood-brain barrier (BBB) damage through degradation of the tight junction proteins (TJs) occludin and ZO-1. Importantly, the experimental results also showed that Cur can alleviate oxidative stress, inflammatory response and BBB injury caused by ATO exposure through Nrf2 and NF-κB signaling pathway. The results suggested Cur exerted as a food additive and provided novel potential benefits of ATO toxicology in inflammation of the brain.

16.
Ecotoxicol Environ Saf ; 221: 112442, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34166936

RESUMO

Arsenic (As) and antimony (Sb) are commonly accumulated environmental pollutants that often coexist in nature and cause serious widespread biological toxicity. To investigate the nephrotoxicity induced by As and Sb in detail, we explored the mechanism by which As and Sb cotreatment induced autophagy and pyroptosis in vivo and in vitro. In this study, mice were treated with 4 mg/kg arsenic trioxide (ATO) or/and 15 mg/kg antimony trichloride (SbCl3) by intragastric intubation for 60 days. TCMK-1 cells were treated with ATO (12.5 µM), SbCl3 (25 µM) or a combination of As and Sb for 24 h. The results of the in vivo experiment demonstrated that As or/and Sb exposure could induce histopathological changes in the kidneys, and increase the levels of biochemical indicators of nephrotoxicity. In addition, As and Sb can co-induce oxidative stress, which further activate autophagy and pyroptosis. In an in vitro experiment, As and/or Sb coexposure increased ROS generation and decreased MMP. Moreover, the results of related molecular experiments further confirmed that As and Sb coactivated autophagy and pyroptosis. In conclusion, our results indicated that As and Sb co-exposure could cause autophagy and pyroptosis via the ROS pathway, and these two metals might have a synergistic effect on nephrotoxicity.


Assuntos
Antimônio/toxicidade , Trióxido de Arsênio/toxicidade , Cloretos/toxicidade , Rim/efeitos dos fármacos , Piroptose/efeitos dos fármacos , Animais , Autofagia/efeitos dos fármacos , Linhagem Celular , Poluentes Ambientais/toxicidade , Rim/fisiopatologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
17.
Ecotoxicol Environ Saf ; 219: 112350, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34022626

RESUMO

Arsenic trioxide (ATO) has been known as common environmental pollution, and is deemed to a threat to global public health. Curcumin (Cur) is a phytoconstituent, which has been demonstrated to have antioxidant effects. In the current experiment, we investigated the efficacy of Cur against ATO-induced kidney injury and explored the potential molecular mechanisms that have not yet been fully elucidated in ducks. The results showed that treatment with Cur attenuated ATO-induced body weight loss, reduced the content of ATO in the kidney, and improved ATO-induced kidney pathological damage. Cur also remarkably alleviated the ascent of ATO-induced MDA level and activated the Nrf2 pathway. Using the TEM, we found Cur relieved mitochondrial swelling, autolysosomes generating and nuclear damage. Simultaneously, Cur was found that it not only significantly reduced autophagy-related mRNA and protein levels (mTOR, LC3-Ⅰ, LC3-Ⅱ, Atg-5, Beclin1, Pink1 and Parkin) and but also decreased apoptosis-related mRNA and protein expression levels (cleaved caspase-3, Cytc, p53 and Bax). Furthermore, through nontargeted metabolomics analysis, we observed that lipid metabolism balance was disordered by ATO exposure, while Cur administration alleviated the disturbance of lipid metabolism. These results showed ATO could induce autophagy and apoptosis by overproducing ROS in the kidney of ducks, and Cur might relieve excessive autophagy, apoptosis and disturbance of lipid metabolism by regulating oxidative stress. Collectively, our findings explicate the potential therapeutic value of Cur as a new strategy to a variety of disorders caused by ATO exposure.


Assuntos
Trióxido de Arsênio/toxicidade , Curcumina/farmacologia , Substâncias Protetoras/farmacologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Patos/metabolismo , Dislipidemias/metabolismo , Rim/efeitos dos fármacos , Nefropatias/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Serina-Treonina Quinases TOR
18.
Ecotoxicol Environ Saf ; 220: 112394, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34091186

RESUMO

Arsenic (As) and antimony (Sb) are known as an environmental contaminant with cardiotoxicity properties. The endoplasmic reticulum (ER) is the largest calcium reservoir in the cell, and its calcium homeostasis disorder plays a vital role in endoplasmic reticulum stress (ERS) and apoptosis. The objective of this study was to investigate whether As and Sb induced apoptosis via endoplasmic reticulum stress (ERS) linked to calcium homeostasis disturbance. In this study, thirty-two adult mice were gavage-fed daily with As2O3 (4 mg/kg), SbCl3 (15 mg/kg) and co-treat with SbCl3 (15 mg/kg) and As2O3 (4 mg/kg) daily for 60 days. It was observed that As or/and Sb caused histopathological lesions and ER expansion of the heart. Meanwhile, the gene expression of ER Ca2+ release channels (RyR2 and IP3R) and calmodulin-dependent protein kinase II (CaMKII) increased while the levels of mRNA and protein of ER Ca2+ uptake channel (SERCA2) downregulated significantly compared to the controls. Then, As or/and Sb induced ERS and triggered the ER apoptotic pathway by activating unfolded protein response (UPR)-associated genes ((PERK, ATF6, IRE1, XBP1, JNK, GRP78), and apoptosis-related genes (Caspase12, Caspase3, p53, CHOP). Above indicators in As + Sb group became more severe than that of As group and Sb group. Overall, our results proved that the cardiotoxicity caused by As or/and Sb might be concerning disturbing calcium homeostasis, which induced apoptosis through the ERS pathway.


Assuntos
Antimônio/toxicidade , Arsênio/toxicidade , Cálcio/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/efeitos dos fármacos , Coração/efeitos dos fármacos , Animais , Antimônio/metabolismo , Apoptose , Arsênio/metabolismo , Canais de Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Cardiotoxicidade/metabolismo , Cardiotoxinas , Caspase 3/metabolismo , Morte Celular , Regulação para Baixo , Retículo Endoplasmático/metabolismo , Chaperona BiP do Retículo Endoplasmático , Poluentes Ambientais/toxicidade , Homeostase/efeitos dos fármacos , Masculino , Metais Pesados/toxicidade , Camundongos , Miocárdio/metabolismo , Miocárdio/patologia , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Resposta a Proteínas não Dobradas
19.
Int J Urol ; 28(6): 689-694, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33783036

RESUMO

OBJECTIVES: To report our single-center experience of the management of children with prostatic utricle cysts. METHODS: We retrospectively analyzed 15 children who were incidentally found to have a prostatic utricle cyst and were admitted to our department between October 2013 and August 2020. Clinical characteristics and management were collected and catalogued. RESULTS: Recurrent genitourinary tract infections were the most frequent complaint, and two-thirds of patients also had hypospadias. A connection between the posterior urethra and the prostatic utricle cyst was found in all cases. Two patients directly had their progressively enlarging prostatic utricle cyst resected laparoscopically. Endoscopic techniques were used in 13 patients, two of whom underwent laparoscopic excision for repeated symptoms. The mean (range) follow-up period was 34.9 (2-82) months. No recurrences were observed in four patients who underwent prostatic utricle cyst excision and eight patients who received endoscopic treatment. Three patients had recurrent symptoms after endoscopic treatment and were managed by nonsurgical treatment. CONCLUSIONS: Prostatic utricle cyst is a rare disease which can cause recurrent genitourinary tract infections. Extra attention should be paid to evaluation for prostatic utricle cyst in children with external genital anomalies. Retrograde urethrogram and magnetic resonance imaging are useful tools with which to distinguish prostatic utricle cyst from other cystic lesions that are located in the midline pelvis in male patients. Individualized treatment is appropriate when considering fertility preservation, recurrences and malignancy. Laparoscopic excision is feasible for symptomatic and large prostatic utricle cyst. Regular long-term monitoring is recommended for all patients with prostatic utricle cyst.


Assuntos
Cistos , Doenças Prostáticas , Criança , Cistos/diagnóstico por imagem , Cistos/cirurgia , Humanos , Masculino , Recidiva Local de Neoplasia , Doenças Prostáticas/cirurgia , Estudos Retrospectivos , Sáculo e Utrículo , Uretra
20.
J Org Chem ; 85(22): 14307-14314, 2020 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-31875676

RESUMO

A H3PO3-catalyzed alkylation of phenols with alkenes is achieved in a facile, efficient, and selective manner. The reaction shows a unique selectivity, i.e., excellent regioselectivity, thorough suppression of overalkylation, without alkylation of a simple phenyl ring, and can selectively provide ortho-, meta-, or para-alkylated phenol derivatives in good to excellent yields. This feature along with mild reaction conditions, sensitive functional group tolerance, and scale-up synthesis and late modification of phenolic bioactive compounds make it an ideal and practical alternative for the modification of phenols.

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