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1.
Can J Gastroenterol Hepatol ; 2022: 6010367, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36111243

RESUMO

Methods: Eligible patients were randomly allocated into the abdominal bandage and conventional groups during a routine colonoscopy. The primary outcome was CCR. Results: A total of 250 eligible patients were randomly assigned to the abdominal bandage and conventional groups from January 2021 to April 2021. Eleven patients (five in the abdominal bandage group and six in the conventional group) were excluded due to schedule cancellation after randomization, and 239 patients were eventually included in the final analysis. There were no significant differences between the two groups regarding baseline characteristics (P > 0.05). Furthermore, no significant differences were observed in terms of advanced adenoma detection rate (AADR), polyp detection rate (PDR), bowel preparation scale (BBPS), bubble scale (BS), and withdrawal time between the two groups (P > 0.05). However, compared with the conventional group, the cecal insertion time (CIT) of the abdominal bandage group was significantly shortened (279.00 (234.50-305.75) vs. 421.00 (327.00-485.00), P < 0.001), and the CCR (96.7% vs. 88.2%, P = 0.01) and adenoma detection rate (ADR) (47.5% vs. 32.8%, P < 0.001) were improved. Besides, logistic regression analysis showed that body mass index (BMI) and abdominal compression bandage were associated with CCR. Conclusions: Abdominal compression bandages could effectively shorten CIT and improve CCR and ADR for obese patients during a routine colonoscopy. This trial is registered with the Chinese Clinical Trial Registry (No. ChiCTR2100043556).


Assuntos
Adenoma , Colonoscopia , Adenoma/diagnóstico , Adulto , Bandagens Compressivas , Humanos , Obesidade/diagnóstico , Estudos Prospectivos
2.
J Immunother ; 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36121316

RESUMO

Immune checkpoint inhibitors (ICIs) are widely used for first-line cisplatin-ineligible patients with metastatic urothelial carcinoma (mUC). However, whether to use ICIs as monotherapy or in combination with chemotherapy is still uncertain. We retrospectively analyzed cisplatin-ineligible patients with mUC who underwent first-line ICI monotherapy or ICI plus chemotherapy at 2 medical centers in Taiwan from 2016 to 2021. We calculated the objective response rate, progression-free survival, and overall survival (OS) using the Kaplan-Meier method and Cox regression model for multivariable analysis. In total, 130 patients were enrolled and categorized into 2 groups: an ICI monotherapy group [immunotherapy (IO), n=101] and an ICI plus noncisplatin chemotherapy group [immunotherapy and chemotherapy (IC), n=29]. The median OS of patients in the IO and IC groups was 19.5 and 9.7 months (P=0.33). Among patients with high programmed cell death ligand-1-expressing tumors, the median OS was significantly prolonged in the IO group compared with the IC group (not reached vs. 6.3 mo, P=0.02). First-line ICI monotherapy demonstrated robust antitumor activity in cisplatin-ineligible patients with mUC. Combining noncisplatin chemotherapy with ICI did not improve clinical outcomes.

3.
Mol Neurobiol ; 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36074232

RESUMO

Purinergic signaling is involved in multiple pain processes. P2X3 receptor is a key target in pain therapeutics, while A1 adenosine receptor signaling plays a role in analgesia. However, it remains unclear whether there is a link between them in pain. The present results showed that the A1 adenosine receptor agonist N6-cyclopentyladenosine (CPA) concentration dependently suppressed P2X3 receptor-mediated and α,ß-methylene-ATP (α,ß-meATP)-evoked inward currents in rat dorsal root ganglion (DRG) neurons. CPA significantly decreased the maximal current response to α,ß-meATP, as shown a downward shift of the concentration-response curve for α,ß-meATP. CPA suppressed ATP currents in a voltage-independent manner. Inhibition of ATP currents by CPA was completely prevented by the A1 adenosine receptor antagonist KW-3902, and disappeared after the intracellular dialysis of either the Gi/o protein inhibitor pertussis toxin, the adenylate cyclase activator forskolin, or the cAMP analog 8-Br-cAMP. Moreover, CPA suppressed the membrane potential depolarization and action potential bursts, which were induced by α,ß-meATP in DRG neurons. Finally, CPA relieved α,ß-meATP-induced nociceptive behaviors in rats by activating peripheral A1 adenosine receptors. These results indicated that CPA inhibited the activity of P2X3 receptors in rat primary sensory neurons by activating A1 adenosine receptors and its downstream cAMP signaling pathway, revealing a novel peripheral mechanism underlying its analgesic effect.

4.
ACS Cent Sci ; 8(8): 1102-1115, 2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36032766

RESUMO

Tumor immune microenvironment (TIME) regulators are promising cancer immunotherapeutic targets. IGF2BP1, as a crucial N 6-methyladenosine (m6A) reader protein, recognizes m6A target transcripts, ultimately leading to cancer development. However, currently, the biological function of IGF2BP1 in regulating the TIME is not well-understood. In this study, we report that IGF2BP1 knockdown induces cancer cell apoptosis, thereby significantly not only activating immune cell infiltration including CD4+, CD8+ T cells, CD56+ NK cells, and F4/80+ macrophage but also decreasing PD-L1 expression in hepatocellular carcinoma (HCC). Then, chemical genetics identifies a small-molecule cucurbitacin B (CuB), which directly targets IGF2BP1 at a unique site (Cys253) in the KH1-2 domains. This leads to a pharmacological allosteric effect to block IGF2BP1 recognition of m6A mRNA targets such as c-MYC, which is highly associated with cell apoptosis and immune response. In vivo, CuB exhibits an obvious anti-HCC effect through inducing apoptosis and subsequently recruits immune cells to tumor microenvironment as well as blocking PD-L1 expression. Collectively, IGF2BP1 may serve as a novel pharmacological allosteric target for anticancer therapeutics via mediating TIME.

5.
J Neurochem ; 2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-35986707

RESUMO

Lysophosphatidic acid (LPA) is a phospholipid which has been implicated in pain. Acid-sensing ion channels (ASICs) are important players in pain associated with tissue acidification. However, it is still unclear whether there is a link between LPA signaling and ASICs in pain processes. Herein, we show that a functional interaction between them in rat dorsal root ganglia (DRG) neurons. Pre-application of LPA enhanced ASIC-mediated and acid-evoked inward currents in a concentration-dependent manner. LPA shifted the concentration-response curve for protons upwards, with an increase of 41.79 ± 4.71% in the maximal current response of ASICs to protons in the presence of LPA. Potentiation of ASIC currents by LPA was blocked by the LPA1 receptor antagonist Ki16198, but not by the LPA2 receptor antagonist H2L5185303. The LPA-induced potentiation was also prevented by intracellular application of either G protein inhibitor or protein kinase C (PKC) inhibitor, but not by Rho inhibitor. LPA also enhanced ASIC3 currents in CHO cells co-expressing ASIC3 and LPA1 receptors, but not in cells expressing ASIC3 alone. Moreover, LPA increased the amplitude of the depolarization and the number of spikes induced by acid stimuli. Finally, LPA exacerbated acid-induced nociceptive behaviors in rats. These results suggested that LPA enhanced ASIC-mediated electrophysiological activity and nociception via a LPA1 receptor and its downstream PKC rather than Rho signaling pathway, which provided a novel peripheral mechanism underlying the sensitization of pain.

6.
Front Pharmacol ; 13: 928647, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35795546

RESUMO

Lysophosphatidic acid (LPA), a lipid metabolite, plays a role in both neuropathic and inflammatory pain through LPA1 receptors. P2X3 receptor has also been shown to participate in these pathological processes. However, it is still unclear whether there is a link between LPA signaling and P2X3 receptors in pain. Herein, we show that a functional interaction between them in rat dorsal root ganglia (DRG) neurons. Pretreatment of LPA concentration-dependently enhanced α,ß-methylene-ATP (α,ß-meATP)-induced inward currents mediated by P2X3 receptors. LPA significantly increased the maximal current response of α,ß-meATP, showing an upward shift of the concentration-response curve for α,ß-meATP. The LPA enhancement was independent on the clamping-voltage. Enhancement of P2X3 receptor-mediated currents by LPA was prevented by the LPA1 receptor antagonist Ki16198, but not by the LPA2 receptor antagonist H2L5185303. The LPA-induced potentiation was also attenuated by intracellular dialysis of either G-protein inhibitor or protein kinase C (PKC) inhibitor, but not by Rho inhibitor. Moreover, LPA significantly changed the membrane potential depolarization and action potential burst induced by α,ß-meATP in DRG neurons. Finally, LPA exacerbated α,ß-meATP- induced nociceptive behaviors in rats. These results suggested that LPA potentiated the functional activity of P2X3 receptors in rat primary sensory neurons through activation of the LPA1 receptor and its downstream PKC rather than Rho signaling pathway, indicating a novel peripheral mechanism underlying the sensitization of pain.

7.
J Med Chem ; 2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35852796

RESUMO

Inhibition of autophagy has been widely viewed as a promising strategy for anticancer therapy. However, few effective and specific autophagy inhibitors have been reported. Herein, we described the design, synthesis, and biological characteristics of new analogues of strigolactones (SLs), an emerging class of plant hormones, against colorectal cancers. Among them, an enantiopure analogue 6 exerted potent and selective cytotoxicity against colorectal cancer cells, but not normal human colon mucosal epithelial cells, which were further confirmed by the plate colony formation assay. Moreover, it significantly inhibited tumor growth in an HCT116 xenograft mouse model with low toxicity. Mechanistically, it is associated with selective induction of cell apoptosis and cell cycle arrest. Remarkably, 6 acted as a potent autophagy/mitophagy inhibitor by selectively increasing the autophagic flux while blocking the autophagosome-lysosome fusion in HCT116 cells. This study features stereo-defined SLs as novel autophagy inhibitors with high cancer cell specificity, which paves a new path for anticolorectal cancer therapy.

8.
Am J Cancer Res ; 12(6): 2659-2672, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35812043

RESUMO

Microscopic vascular invasion (MVI) is a strong risk factor associated with tumor recurrence and poor overall survival (OS) among hepatocellular carcinoma (HCC) patients after resection. Two types of MVI are identified: portal vein and capsular vein invasion. However, little is known about the impact of different types of MVI on HCC recurrence. The present study aimed to compare HCC recurrence and OS between the portal vein and capsule vein MVI. Patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A HCC who underwent primary resection between January 2001 and June 2016 were consecutively recruited. Factors that influenced OS and recurrence-free survival (RFS) were analyzed using Cox proportional hazards models. Of the 857 eligible patients, 327 (38.2%) had MVI, and 530 (61.8%) were without MVI. Of the 327 patients with MVI, 85 (26.0%) were with portal vein, 178 (54.4%) with capsular vein, and 64 (19.6%) with both-MVI type. Patients with both-MVI type suffered from a higher proportion of BCLC stage A (P < 0.001), capsular invasion (P = 0.002), and satellite nodules (P < 0.001). Both-MVI type is an independent risk factor for HCC recurrence (hazard ratio [HR]: 1.69; 95% CI, 1.22-2.36, P = 0.002) and mortality (HR: 2.29; 95% CI, 1.59-3.29, P < 0.001) compared with non-MVI. We further found that both-MVI type was significantly associated with a higher risk of extrahepatic recurrence (EHR) (HR: 8.74; 95% CI, 2.38-32.03, P = 0.001). Among HCC patients after curative resection, concurrent portal and capsular MVI is a risk factor for HCC recurrence, especially for EHR, in comparison with non-MVI or only portal or capsular MVI alone.

9.
Int J Mol Sci ; 23(13)2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35805931

RESUMO

Arsenicals have been widely used in the treatment of cancers such as leukemia and other tumors. However, their side effects limit their clinical application. Stiripentol, a second-line adjunctive treatment for epilepsy with a good safety profile, inhibits microsomal cytochrome-P450-family enzymes to extend the retention time of co-administration. Inspired by the metabolism of stiripentol, the 1,3-benzodioxole responsible for the inhibition and its metabolic derivatives were conjugated with arsenical precursors. The fabricated arsenicals were eliminated much slower in mice and maintained an efficient concentration in the blood for a longer time than that of the arsenical precursors. They also performed better in anti-proliferation by inhibiting the thioredoxin system to induce oxidative stress, and concomitantly to initiate apoptosis in vitro and in vivo. The fabricated arsenicals reversed the hemogram of tumor-bearing mice to normal and eliminated the tumor without causing damage to any organs, exhibiting a good design strategy and pre-clinical application for leukemia and other tumors.


Assuntos
Arsenicais , Leucemia , Neoplasias , Animais , Apoptose , Arsenicais/farmacologia , Arsenicais/uso terapêutico , Dioxóis , Leucemia/tratamento farmacológico , Camundongos , Neoplasias/patologia
10.
J Agric Food Chem ; 2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35879021

RESUMO

The objective of this study is to find new selective allelochemicals for managing two problematic weeds redroot pigweed (Amaranthus retroflexus) and common lambsquarters (Chenopodium album) with minimal negative effects on wheat, thereby facilitating the development of eco-friendly botanical herbicide. Three new sesquiterpenoids, sonarvenolide A-C (1-3), and nine known sesquiterpenoids (4-12) were isolated from Sonchus arvensis. Compound 1 was a rare peroxide-substituted eudesmane-type sesquiterpenoid, and compound 3 was a rare iphionane-type sesquiterpenoid. Notably, compounds 1, 3, 4, 6-8, and 11 showed selectivity phytotoxic activity. In particular, compounds 1, 3, and 4 exhibited excellent germination inhibitory effect on A. retroflexus (IC50 = 32.0-129.0 µM), higher than that of the positive control triasulfuron (IC50 = 141.7 µM), and compound 4 showed excellent inhibition on C. album (IC50 = 82.0 µM), higher than that of triasulfuron (IC50 = 100.9 µM). In addition, compounds 1, 3, and 4 showed allelopathy to the growth of two weeds, which were more potent than or close to that of triasulfuron. Furthermore, these compounds were not toxic to wheat even at a high concentration (1000 µM). Structure-activity relationships (SARs) revealed that the presence of peroxides or the absence of hydroxyl at C-5 in the eudesmane-type sesquiterpenoids could strengthen the inhibitory activities. The discovery of selective allelochemicals provides not only a new choice to control two problematic weeds of wheat but also new natural lead compounds for herbicides.

11.
J Pers Med ; 12(6)2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35743699

RESUMO

Estrogen and progesterone are the major determinants of the occurrence and development of endometrial cancer (EC), which is one of the most common gynecological cancers worldwide. Our purpose was to develop a novel estrogen/progesterone-related gene signature to better predict the prognosis of EC and help discover effective therapeutic strategies. We downloaded the clinical and RNA-seq data of 397 EC patients from The Cancer Genome Atlas (TCGA) database. The "limma" R package was used to screen for estrogen/progesterone-related differentially expressed genes (DEGs) between EC and normal tissues. Univariate and multivariate Cox proportional hazards regression analyses were applied to identify these DEGs that were associated with prognosis; then, a novel estrogen/progesterone-related prognostic signature comprising CDC25B, GNG3, ITIH3, PRXL2A and SDHB was established. The Kaplan-Meier (KM) survival analysis showed that the low-risk group identified by this signature had significantly longer overall survival (OS) than the high-risk group; the receiver operating characteristic (ROC) and risk distribution curves suggested this signature was an accurate predictor independent of risk factors. A nomogram incorporating the signature risk score and stage was constructed, and the calibration plot suggested it could accurately predict the survival rate. Compared with normal tissues, tumor tissues had increased mRNA levels of GNG3 and PRXL2A and a reduced mRNA level of ITIH3. The knockdown of PRXL2A and GNG3 significantly inhibited the proliferation and colony formation of Ishikawa and AN3CA cells, while the inhibition of PRXL2A expression suppressed xenograft growth. In this study, five estrogen/progesterone-related genes were identified and incorporated into a novel signature, which provided a new classification tool for improved risk assessment and potential molecular targets for EC therapies.

12.
J Transl Med ; 20(1): 260, 2022 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-35672776

RESUMO

BACKGROUND: Lung adenocarcinoma (LUAD) is a heavy social burden worldwide. Because the mechanisms involved in LUAD remain unclear, the prognosis of LUAD remains poor. Consequently, it is urgent to investigate the potential mechanisms of LUAD. Junctional adhesion molecule-like protein (JAML), is recognized as a tumorigenesis molecule in gastric cancer. However, the role of JAML in LUAD is still unclear. Here we aimed to evaluate the role of JAML in LUAD. METHODS: qRT-PCR, Western blotting and immunohistochemistry were conducted to investigate the expression of JAML in LUAD tissues. JAML was knocked down and overexpressed in LUAD cells using transient transfection by siRNA and plasmids or stable transfection by lentivirus. Proliferation potential of LUAD cells were detected by Cell Counting Kit-8, EdU incorporation and Colony formation assay. Migration and invasion abilities of LUAD cells were determined by wound healing, transwell migration and invasion assays. Cell cycle and cell apoptosis were detected by flow cytometry. The effects of JAML in vivo were studied in xenograft tumor models. Western blotting was used to explore the molecular mechanisms of JAML function. In addition, rescue experiments were performed to verify the possible mechanisms. RESULTS: JAML expression was elevated in LUAD tissues compared with peritumor tissues, and this upregulation was positively related to pT and pTNM. Furthermore, both in vitro and in vivo, JAML silencing markedly repressed malignant behaviors of LUAD cells and vice versa. Knockdown of JAML also mediated cell cycle arrest at G0/G1 phase and promoted apoptosis in LUAD cells. Mechanistically, silencing JAML repressed the process of epithelial-mesenchymal transition by inactivating the Wnt/ß-catenin pathway in LUAD cells. Effects of JAML can be rescued by Wnt/ß-catenin pathway activator in A549 cells. CONCLUSIONS: Our data reveal the oncogenic role of JAML in LUAD, indicating that JAML may be a predictive biomarker and novel therapeutic target for LUAD.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Moléculas de Adesão Celular/metabolismo , Neoplasias Pulmonares , Adenocarcinoma/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Moléculas de Adesão Juncional/genética , Moléculas de Adesão Juncional/metabolismo , Neoplasias Pulmonares/patologia , Via de Sinalização Wnt , beta Catenina/metabolismo
13.
Front Pediatr ; 10: 873035, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35676904

RESUMO

Purpose: To develop and validate a machine learning-based CT radiomics method for preoperatively predicting the stages (stage I and non-stage I) of Wilms tumor (WT) in pediatric patients. Methods: A total of 118 patients with WT, who underwent contrast-enhanced computed tomography (CT) scans in our center between 2014 and 2021, were studied retrospectively and divided into two groups: stage I and non-stage I disease. Patients were randomly divided into training cohorts (n = 94) and test cohorts (n = 24). A total of 1,781 radiomic features from seven feature classes were extracted from preoperative portal venous-phase images of abdominal CT. Synthetic Minority Over-Sampling Technique (SMOTE) was used to handle imbalanced datasets, followed by a t-test and Least Absolute Shrinkage and Selection Operator (LASSO) regularization for feature selection. Support Vector Machine (SVM) was deployed using the selected informative features to develop the predicting model. The performance of the model was evaluated according to its accuracy, sensitivity, and specificity. The receiver operating characteristic curve (ROC) and the area under the ROC curve (AUC) was also arranged to assess the model performance. Results: The SVM model was fitted with 15 radiomic features obtained by t-test and LASSO concerning WT staging in the training dataset and demonstrated favorable performance in the testing dataset. Cross-validated AUC on the training dataset was 0.79 with a 95 percent confidence interval (CI) of 0.773-0.815 and a coefficient of variation of 3.76%, while AUC on the test dataset was 0.81, and accuracy, sensitivity, and specificity were 0.79, 0.87, and 0.69, respectively. Conclusions: The machine learning model of SVM based on radiomic features extracted from CT images accurately predicted WT stage I and non-stage I disease in pediatric patients preoperatively, which provided a rapid and non-invasive way for investigation of WT stages.

14.
Oncogene ; 41(30): 3791-3803, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35764885

RESUMO

Glioblastoma is a lethal primary brain tumor with abundant immune-suppressive glioblastoma-associated macrophage (GAM) infiltration. Skewing immune suppressive GAMs towards an immune-activating phenotype represents a promising immunotherapeutic strategy against glioblastoma. Herein, we reported that genetic deletion of miRNA-processing enzyme Dicer in macrophages inhibited the growth of GL261 murine glioblastoma xenografts and prolonged survival of tumor-bearing mice. Single cell RNA sequencing (scRNA-seq) of the tumor-infiltrating immune cells revealed that Dicer deletion in macrophages reduced the proportion of cell-cycling GAM cluster and reprogramed the remaining GAMs towards a proinflammatory activation state (enhanced phagocytotic and IFN-producing signature). Dicer-deficient GAMs showed reduced level of cyclin-dependent kinases (CDK1 and CDK2) and increased expression of CDK inhibitor p27 Kip1, thus manifesting impaired proliferation. Dicer knockout enhanced phagocytotic activity of GAMs to eliminate GL261 tumor cells. Increased proinflammatory GAM clusters in macrophage Dicer-deficient mice actively interacted with tumor-infiltrating T cells and NK cells through TNF paracrine signaling to create a pro-inflammatory immune microenvironment for tumor cell elimination. Our work identifies the role of Dicer deletion in macrophages in generating an immune-activating microenvironment, which could be further developed as a potential immunotherapeutic strategy against glioblastoma.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Animais , Neoplasias Encefálicas/patologia , Proliferação de Células/genética , Glioblastoma/metabolismo , Humanos , Células Matadoras Naturais/metabolismo , Macrófagos/metabolismo , Camundongos , Linfócitos T/metabolismo , Microambiente Tumoral/genética
15.
Rev. esp. enferm. dig ; 114(6): 343-347, junio 2022. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-205654

RESUMO

Introduction and aim: duodenal subepithelial lesions (SELs) are increasingly detected during endoscopic examinations. However, no feasible and safe methods are available to remove duodenal SELs. The present study aimed to assess the feasibility and safety of endoscopic resection in combination with ligation (ER-L) for the removal of duodenal SELs.Patients and methods: a total of 101 patients with duodenal SELs underwent ER-L from February 2010 to February 2020. The primary outcomes were complete resection, en bloc resection and R0 resection. The secondary outcomes included procedure duration, bleeding, perforation and residual lesions. A total of 101 patients with 101 duodenal SELs (ranged from 8.4 mm to 20.2 mm in size) were included in the study.Results: most of the SELs (95.1 %) originated from the submucosal layer and were successfully removed using ER-L. The rates of complete resection, en bloc resection and R0 resection were 100 %, 96.0 % and 88.1 %, respectively. The median procedure duration was eight minutes. There were no severe complications, except for four patients who developed post-procedure bleeding (4.0 %) and recovered after conservative treatment. Furthermore, no residual lesions were detected during the follow-up period (median of 36 months). In fact, logistic regression analysis showed that the size of duodenal SELs was an independent factor for R0 resection during the ER-L procedure.Conclusion: in conclusion, ER-L is feasible and safe to remove duodenal SELs that originate from the submucosal layer and are less than 20 mm. However, the feasibility and safety of the ER-L should be further confirmed when removing the duodenal SELs that originate from the muscularis propria (MP) layer and are larger than 20 mm in diameter. (AU)


Assuntos
Humanos , Neoplasias Duodenais/patologia , Neoplasias Duodenais/cirurgia , Duodeno/patologia , Ressecção Endoscópica de Mucosa/métodos , Ligadura , Neoplasias Gástricas , Estudos Retrospectivos , Resultado do Tratamento
17.
ACS Nano ; 2022 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35622408

RESUMO

Carbon quantum dots (CQDs) offer huge potential due to their enzymatic properties as compared to natural enzymes. Thus, discovery of CQDs-based nanozymes with low toxicity from natural resources, especially daily food, implies a promising direction for exploring treatment strategies for human diseases. Here, we report a CQDs-based biocompatible nanozyme prepared from chlorogenic acid (ChA), a major bioactive natural product from coffee. We found that ChA CQDs exhibited obvious GSH oxidase-like activities and subsequently promoted cancer cell ferroptosis by perturbation of GPX4-catalyzed lipid repair systems. In vivo, ChA CQDs dramatically suppressed the tumor growth in HepG2-tumor-bearing mice with negligible side toxicity. Particularly, in hepatoma H22-bearing mice, ChA CQDs recruited massive tumor-infiltrating immune cells including T cells, NK cells, and macrophages, thereby converting "cold" to "hot" tumors for activating systemic antitumor immune responses. Taken together, our study suggests that natural product-derived CQDs from coffee can serve as biologically safe nanozymes for anticancer therapeutics and may aid the development of nanotechnology-based immunotherapeutic.

19.
J Neurosci Res ; 100(9): 1755-1764, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35592934

RESUMO

Resveratrol can relieve pain under various pain conditions. One of the mechanisms of resveratrol analgesia is the regulation of ion channels. Acid-sensing ion channels (ASICs) are expressed predominantly in nociceptive sensory neurons to detect changes in extracellular pH. ASICs are important players in pain associated with tissue acidification. However, it is still unclear whether ASICs are resveratrol targets. Electrophysiological recordings showed that resveratrol decreased acid-induced and ASIC-mediated currents in male rat dorsal root ganglion (DRG) neurons in a concentration-dependent manner. Resveratrol downwardly shifted the concentration-response curve for protons, suggesting that it inhibited ASICs not by changing the pH0.5 , but by suppressing the proton-induced maximum response. It also suppressed acid-triggered action potentials in the rat DRG neurons. Finally, intraplantar pretreatment with resveratrol relieved acid-induced nociceptive responses in male rats in a dose-dependent manner. These results indicated that resveratrol inhibited ASIC-mediated electrophysiological activity and nociception, suggesting a novel peripheral mechanism underlying its analgesic effect.


Assuntos
Canais Iônicos Sensíveis a Ácido , Gânglios Espinais , Animais , Gânglios Espinais/fisiologia , Masculino , Dor/induzido quimicamente , Dor/tratamento farmacológico , Prótons , Ratos , Ratos Sprague-Dawley , Resveratrol , Células Receptoras Sensoriais
20.
World J Pediatr ; 18(9): 598-606, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35536454

RESUMO

BACKGROUND: Asthma mortality among children and adolescents at the national level in China was unreported. The aim of this study was to analyze the mortality of asthma among children and adolescents in China using a nationally representative database. METHODS: This was a descriptive study using data from the Disease Surveillance Points (DSPs) system. All asthma-related deaths among children and adolescents aged 0-19 years occurring in DSPs across China from 2008 to 2018 were included. Multilevel Poisson regression models were used to compute the total, age-, gender-, region- and residence-specific asthma mortality rates and to investigate the significance of trends and factors associated with asthma mortality. Data from the National Bureau of Statistics were used to estimate the national asthma deaths. RESULTS: Total asthma mortality rate among Chinese children and adolescents fluctuated between 0.020 (0.009, 0.045) and 0.059 (0.025, 0.137) per 100,000 and showed an overall downward trend (RR, 0.909; 95% CI 0.854-0.968) during the study period (2008-2018). Asthma mortality rate was higher in the western China (RR 2.356, 95% CI 1.513, 3.669) and varied over a ninefold range among DSPs in China. The estimated number of deaths decreased by 51.38% from 2008 (n = 148; 95% CI 58,379) to 2018 (n = 71; 95% CI 34, 109). CONCLUSIONS: Asthma mortality rate among children and adolescents in China was at a low level compared to rates worldwide and decreased significantly from 2008 to 2018. Compared with most countries in the world, the number of asthma deaths was higher in China.


Assuntos
Asma , Adolescente , Criança , China/epidemiologia , Bases de Dados Factuais , Humanos
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