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1.
BMC Anesthesiol ; 24(1): 380, 2024 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-39438789

RESUMO

BACKGROUND: Postoperative pain management remains a significant challenge for patients undergoing posterior urethroplasty (PU). In a previous study, we proposed a novel technique of combined pudendal nerve (PN) and spermatic cord (SC) block to manage pain after PU. The present trial was conducted to test the hypothesis that this technique is effective for pain control after PU and provides longer-lasting analgesia than caudal epidural block (CB). METHODS: Sixty patients undergoing PU were randomized into two groups: Group NB received combined PN and SC block, and Group CB received CB. General anesthesia with a laryngeal mask was performed. The primary outcome was the postoperative analgesic duration, and the secondary outcomes included the Numeric Rating Scale (NRS) scores for pain and the number of patients with different motor scores of the lower limb at 3, 6, 12, and 24 h postoperatively. RESULTS: Two patients in Group CB were withdrawn due to block failure. The postoperative analgesic duration was statistically longer in Group NB compared with Group CB (mean difference [95% confidence interval], 115.78 min [17.80, 213.75]; P = 0.021). The NRS scores for pain at 12 and 24 h after surgery were statistically lower in Group NB compared with Group CB. Group NB had statistically more patients with motor score 0 at 3 h postoperatively than Group CB. CONCLUSIONS: PN combined with SC block is an effective technique for postoperative analgesia in PU. This technique can achieve a longer duration of analgesia and lower pain scores, especially 12 h after surgery, than a CB. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Register (registration no. ChiCTR2100042971, registration date on 2/2/2021).


Assuntos
Bloqueio Nervoso , Dor Pós-Operatória , Nervo Pudendo , Cordão Espermático , Humanos , Masculino , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/tratamento farmacológico , Bloqueio Nervoso/métodos , Adulto , Pessoa de Meia-Idade , Cordão Espermático/inervação , Cordão Espermático/cirurgia , Uretra/cirurgia , Uretra/inervação , Anestesia Caudal/métodos , Medição da Dor/métodos
2.
Eur Radiol ; 33(10): 7238-7249, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37145148

RESUMO

OBJECTIVES: We applied a fully automated pixel-wise post-processing framework to evaluate fully quantitative cardiovascular magnetic resonance myocardial perfusion imaging (CMR-MPI). In addition, we aimed to evaluate the additive value of coronary magnetic resonance angiography (CMRA) to the diagnostic performance of fully automated pixel-wise quantitative CMR-MPI for detecting hemodynamically significant coronary artery disease (CAD). METHODS: A total of 109 patients with suspected CAD were prospectively enrolled and underwent stress and rest CMR-MPI, CMRA, invasive coronary angiography (ICA), and fractional flow reserve (FFR). CMRA was acquired between stress and rest CMR-MPI acquisition, without any additional contrast agent. Finally, CMR-MPI quantification was analyzed by a fully automated pixel-wise post-processing framework. RESULTS: Of the 109 patients, 42 patients had hemodynamically significant CAD (FFR ≤ 0.80 or luminal stenosis ≥ 90% on ICA) and 67 patients had hemodynamically non-significant CAD (FFR ˃ 0.80 or luminal stenosis < 30% on ICA) were enrolled. On the per-territory analysis, patients with hemodynamically significant CAD had higher myocardial blood flow (MBF) at rest, lower MBF under stress, and lower myocardial perfusion reserve (MPR) than patients with hemodynamically non-significant CAD (p < 0.001). The area under the receiver operating characteristic curve of MPR (0.93) was significantly larger than those of stress and rest MBF, visual assessment of CMR-MPI, and CMRA (p < 0.05), but similar to that of the integration of CMR-MPI with CMRA (0.90). CONCLUSIONS: Fully automated pixel-wise quantitative CMR-MPI can accurately detect hemodynamically significant CAD, but the integration of CMRA obtained between stress and rest CMR-MPI acquisition did not provide significantly additive value. KEY POINTS: • Full quantification of stress and rest cardiovascular magnetic resonance myocardial perfusion imaging can be postprocessed fully automatically, generating pixel-wise myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) maps. • Fully quantitative MPR provided higher diagnostic performance for detecting hemodynamically significant coronary artery disease, compared with stress and rest MBF, qualitative assessment, and coronary magnetic resonance angiography (CMRA). • The integration of CMRA and MPR did not significantly improve the diagnostic performance of MPR alone.


Assuntos
Doença da Artéria Coronariana , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Imagem de Perfusão do Miocárdio , Humanos , Doença da Artéria Coronariana/diagnóstico , Angiografia Coronária/métodos , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Constrição Patológica , Valor Preditivo dos Testes , Perfusão , Imagem de Perfusão do Miocárdio/métodos
3.
Immunol Invest ; 52(3): 298-318, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36731128

RESUMO

BACKGROUND: M2-type macrophages are inflammation-suppressing cells that are differentiated after induction by cytokines such as IL-4 or IL-13, which play an important regulatory role in inflammation and influence the regression of inflammation-related diseases. All-trans retinoic acid (ATRA) has an important role in suppressing immune-mediated inflammatory responses but the effect and underlying mechanism of ATRA on the polarization of M2 macrophages remains unclear. METHODS: Macrophages were isolated from peritoneal wash fluid, and IL-4 (20 ng/mL) was used to construct a m2-type macrophage polarization model. The model was incubated with different concentrations of ATRA (15 µg/ml, 30 µg/ml, 45 µg/ml) for 24 h, and pretreated macrophages with p38MAPKα inhibitor SB202190 (20 µM). MTT, Trypan blue staining, Annexin V-PE/7-AAD staining, flow cytometry, real-time PCR and western blotting were used to investigate the effect and mechanism of ATRA on the polarization of M2 macrophages. RESULTS: Compared with the IL-4 group, the proportion of F4/80+CD206+ M2-type macrophages was significantly higher in the ATRA group (P < 0.01). mRNA and protein expression levels of Arg-1, IL-10 and TGF-ß1 were as significantly higher (P < 0.01) in the ATRA group as phosphorylation levels of STAT6 and p38MAPK (P < 0.01). After pretreatment with the addition of the inhibitor SB202190, M2-type macrophages proportion and their associated factors expression were significantly (P < 0.01) reduced, as compared with those in the ATRA group, but they were comparable (P > 0.05) with the IL-4 group. CONCLUSION: The combination of ATRA and IL-4 activated the p38MAPK/STAT6-signaling pathway to promote polarization of M2 macrophages.


Assuntos
Interleucina-4 , Macrófagos , Tretinoína , Humanos , Inflamação/metabolismo , Sistema de Sinalização das MAP Quinases , Fator de Transcrição STAT6/metabolismo , Tretinoína/farmacologia
4.
BMC Anesthesiol ; 22(1): 334, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319962

RESUMO

BACKGROUND: Developing adequate regional anaesthesia for knee surgeries without affecting lower limb mobilization is crucial to perioperative analgesia. However, reports in this regard are limited. We proposed a technique for ultrasound-guided peripatellar plexus (PP) block. Compared with the femoral nerve (FN) block, we hypothesized that this technique would provide a noninferior block duration and a complete cutaneous sensory block in the peripatellar region without affecting lower limb mobilization. An investigation was conducted to verify our hypothesis in cadavers and volunteers. METHODS: The study was designed in two parts. First, eight cadaveric lower limbs were dissected to verify the feasibility of PP block after methylene blue injection under ultrasound. Second, using a noninferiority study design, 50 healthy volunteers were randomized to receive either a PP block (PP group) or an FN block (FN group). The primary outcome was the duration of peripatellar cutaneous sensory block, with the prespecified noninferiority margin of -3.08 h; the secondary outcome was the area of peripatellar cutaneous sensory block; in addition, the number of complete anaesthesias of the incision line for total knee arthroplasty and the Bromage score 30 min after block were recorded. RESULTS: The PP was successfully dyed, whereas the FN and saphenous nerve were unstained in all cadaveric limbs. The mean difference of the block duration between the two groups was - 1.24 (95% CI, -2.81 - 0.33) h, and the lower boundary of the two-sided 95% CI was higher than the prespecified noninferiority margin (Pnoninferiority = 0.023), confirming the noninferiority of our technique over FN block. The cutaneous sensory loss covered the entire peripatellar region in the PP group. PP block achieved complete anaesthesia of the incision line used for total knee arthroplasty and a Bromage score of 0 in 25 volunteers, which differed significantly from that of volunteers who underwent FN block. CONCLUSION: Ultrasound-guided PP block is a feasible technique. Compared with FN block, PP block provides noninferior block duration and complete blocking of the peripatellar region without affecting lower limb mobilization. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Register (registration no. ChiCTR2000041547, registration date 28/12/2020).


Assuntos
Anestesia por Condução , Bloqueio Nervoso , Humanos , Nervo Femoral , Bloqueio Nervoso/métodos , Anestésicos Locais , Cadáver , Ultrassonografia de Intervenção/métodos , Dor Pós-Operatória
5.
Cancer Sci ; 112(6): 2349-2360, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33565687

RESUMO

Reliable and noninvasive biomarkers for the early diagnosis of non-small-cell lung cancer (NSCLC) are an unmet need. This study aimed to screen and validate potential urinary biomarkers for the early diagnosis of NSCLC. Using protein mass spectrometry, urinary MDH2 was found to be abundant both in patients with lung cancer and lung cancer model mice compared with controls. Urine samples obtained as retrospective and prospective cohorts including 1091 NSCLC patients and 736 healthy controls were measured using ELISA. Patients with stage I NSCLC had higher urinary MDH2 compared with healthy controls. The area under the receiver-operating characteristic curve (AUC) for the urinary MDH2 was 0.7679 and 0.7234 in retrospective and prospective cohorts to distinguish stage I cases from controls. Urinary MDH2 levels correlated with gender and smoking history. MDH2 expression levels were elevated in lung cancer tissues. MDH2 knockdown using shRNA inhibited the proliferation of lung cancer cells. Our study demonstrated that urinary MDH2 concentration was higher in early-stage NSCLC patients compared with that in controls and that MDH2 could serve as a potential biomarker for early detection of NSCLC.


Assuntos
Biomarcadores Tumorais/urina , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Malato Desidrogenase/urina , Regulação para Cima , Células A549 , Animais , Área Sob a Curva , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/urina , Estudos de Casos e Controles , Linhagem Celular Tumoral , Detecção Precoce de Câncer , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Espectrometria de Massas , Camundongos , Estadiamento de Neoplasias , Transplante de Neoplasias , Estudos Prospectivos , Estudos Retrospectivos
6.
J Org Chem ; 86(22): 16114-16120, 2021 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-33416327

RESUMO

We developed an electrochemical trifluoromethylation of thiophenols without the use of metal catalysts and oxidants. This reaction features mild reaction conditions, readily available substrate, as well as moderate to good yields. In addition, this protocol can be easily scaled up with moderate efficiency.


Assuntos
Hidrocarbonetos Fluorados , Mesilatos , Fenóis , Compostos de Sulfidrila
7.
Apoptosis ; 24(3-4): 312-325, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30710195

RESUMO

Gasdermin E (GSDME) has an important role in inducing secondary necrosis/pyroptosis. Upon apoptotic stimulation, it can be cleaved by activated caspase-3 to generate its N-terminal fragment (GSDME-NT), which executes pyroptosis by perforating the plasma membrane. GSDME is expressed in many human lung cancers including A549 cells. Paclitaxel and cisplatin are two representative chemotherapeutic agents for lung cancers, which induce apoptosis via different action mechanisms. However, it remains unclear whether they can induce GSDME-mediated secondary necrosis/pyroptosis in lung A549 cancer cells. Here we showed that both paclitaxel and cisplatin evidently induced apoptosis in A549 cells as revealed by the activation of multiple apoptotic markers. Notably, some of the dying cells displayed characteristic morphology of secondary necrosis/pyroptosis, by blowing large bubbles from the cellular membrane accompanied by caspase-3 activation and GSDME-NT generation. But the ability of cisplatin to induce this phenomenon was much stronger than that of paclitaxel. Consistent with this, cisplatin triggered much higher activation of caspase-3 and generation of GSDME-NT than paclitaxel, suggesting that the levels of secondary necrosis/pyroptosis correlated with the levels of active caspase-3 and GSDME-NT. Supporting this, caspase-3 specific inhibitor (Ac-DEVD-CHO) suppressed cisplatin-induced GSDME-NT generation and concurrently reduced the secondary necrosis/pyroptosis. Besides, GSDME knockdown significantly inhibited cisplatin- but not paclitaxel-induced secondary necrosis/pyroptosis. These results indicated that cisplatin induced higher levels of secondary necrosis/pyroptosis in A549 cells than paclitaxel, suggesting that cisplatin may provide additional advantages in the treatment of lung cancers with high levels of GSDME expression.


Assuntos
Antineoplásicos/farmacologia , Caspase 3/metabolismo , Cisplatino/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/farmacologia , Piroptose/efeitos dos fármacos , Receptores de Estrogênio/metabolismo , Células A549 , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/metabolismo , Necrose/tratamento farmacológico , Necrose/metabolismo
8.
Apoptosis ; 24(9-10): 703-717, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31175486

RESUMO

ATP acts as a canonical activator to induce NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome activation in macrophages, leading to caspase-1/gasdermin D (GSDMD)-mediated pyroptosis. It remains unclear whether ATP can induce pyroptosis in macrophages when the NLRP3 pathway is blocked by pathogenic infection. In this study, we used cellular models to mimic such blockade of NLRP3 activation: bone marrow-derived macrophages (BMDMs) treated with NLRP3-specific inhibitor MCC950 and RAW264.7 cells deficient in ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) expression. The results showed that ATP treatment induced lytic cell death morphologically resembling canonical pyroptosis in both MCC950-treated BMDMs and RAW264.7 cells, but did not cause the activation of caspase-1 (by detecting caspase-1p10 and mature interleukin-1ß) and cleavage of GSDMD. Instead, both apoptotic initiator (caspase-8 and -9) and executioner (caspase-3 and -7) caspases were evidently activated and gasdermin E (GSDME) was cleaved to generate its N-terminal fragment (GSDME-NT) which executes pyroptosis. The GSDME-NT production and lytic cell death induced by ATP were diminished by caspase-3 inhibitor. In BMDMs without MCC950 treatment, ATP induced the formation of ASC specks which were co-localized with caspase-8; with MCC950 treatment, however, ATP did not induced the formation of ASC specks. In RAW264.7 cells, knockdown of GSDME by small interfering RNA attenuated ATP-induced lytic cell death and HMGB1 release into culture supernatants. Collectively, our results indicate that ATP induces pyroptosis in macrophages through the caspase-3/GSDME axis when the canonical NLRP3 pathway is blocked, suggestive of an alternative mechanism for combating against pathogen evasion.


Assuntos
Trifosfato de Adenosina/farmacologia , Caspase 3/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas de Neoplasias/metabolismo , Piroptose/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Animais , Caspase 1/metabolismo , Caspase 8/metabolismo , Caspases/metabolismo , Inflamassomos/metabolismo , Macrófagos/metabolismo , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Células RAW 264.7 , Interferência de RNA
9.
J Gastroenterol Hepatol ; 34(9): 1497-1503, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31062380

RESUMO

BACKGROUND AND AIM: Familial adenomatous polyposis (FAP) is the most common adenomatous polyposis syndrome. Patients with FAP are screened for germline mutations of two genes, APC and MUTYH. However, limited data exist on the clinical characterization and genotypic spectrum of FAP in China. This study was aimed to determine APC and MUTYH mutational status in a small cohort of FAP probands in China and to characterize the genotype-phenotype correlation in mutated patients. METHODS: Mutation screening of 46 unrelated probands was performed using multigene panels by next-generation sequencing. Clinical data of the index were used to assess genotype-phenotype correlations. RESULTS: Overall, 42 out of 46 (91.30%) unrelated probands found mutations, including 35 (76.09%) with APC mutations, 3 (6.52%) with MUTYH mutations, and 4 (8.70%) with both APC and MUTYH mutations. Ten APC genetic alterations variants were novel. The hereditary pattern of the family with both APC and MUTYH mutations was autosomal dominant inheritance. Upper gastrointestinal polyp was the most common extracolonic manifestations. The onset time for patients with both APC and MUTYH mutations was earlier than MUTYH mutation carriers and similar to APC mutation carriers. But the age of carcinogenesis for patients with both APC and MUTYH mutations was later than APC mutation carriers and similar to MUTYH mutation carriers. CONCLUSION: In this study, we show the importance of using multigene panels that allow for a parallel comprehensive screening. We suggest that genetic testing of patients with suspected adenomatous polyposis syndromes should include APC and MUTYH gene mutation analyses simultaneously.


Assuntos
Proteína da Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/genética , DNA Glicosilases/genética , Mutação , Polipose Adenomatosa do Colo/diagnóstico , Polipose Adenomatosa do Colo/etnologia , Povo Asiático/genética , Pequim/epidemiologia , Estudos de Associação Genética , Predisposição Genética para Doença , Hereditariedade , Humanos , Taxa de Mutação , Linhagem , Fenótipo
10.
Cell Physiol Biochem ; 45(4): 1444-1454, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29466793

RESUMO

BACKGROUND/AIMS: Colonoscopy screening has been accepted broadly to evaluate the risk and incidence of colorectal cancer (CRC) during health examination in outpatients. However, the intrusiveness, complexity and discomfort of colonoscopy may limit its application and the compliance of patients. Thus, more reliable and convenient diagnostic methods are necessary for CRC screening. Genome instability, especially copy-number variation (CNV), is a hallmark of cancer and has been proved to have potential in clinical application. METHODS: We determined the diagnostic potential of chromosomal CNV at the arm level by whole-genome sequencing of CRC plasma samples (n = 32) and healthy controls (n = 38). Arm level CNV was determined and the consistence of arm-level CNV between plasma and tissue was further analyzed. Two methods including regular z score and trained Support Vector Machine (SVM) classifier were applied for detection of colorectal cancer. RESULTS: In plasma samples of CRC patients, the most frequent deletions were detected on chromosomes 6, 8p, 14q and 1p, and the most frequent amplifications occurred on chromosome 19, 5, 2, 9p and 20p. These arm-level alterations detected in plasma were also observed in tumor tissues. We showed that the specificity of regular z score analysis for the detection of colorectal cancer was 86.8% (33/38), whereas its sensitivity was only 56.3% (18/32). Applying a trained SVM classifier (n = 40 in trained group) as the standard to detect colorectal cancer relevance ratio in the test samples (n = 30), a sensitivity of 91.7% (11/12) and a specificity 88.9% (16/18) were finally reached. Furthermore, all five early CRC patients in stages I and II were successfully detected. CONCLUSION: Trained SVM classifier based on arm-level CNVs can be used as a promising method to screen early-stage CRC.


Assuntos
Cromossomos/metabolismo , Neoplasias Colorretais/diagnóstico , DNA/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneuploidia , Área Sob a Curva , Estudos de Casos e Controles , Cromossomos/genética , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , DNA/genética , DNA/metabolismo , Variações do Número de Cópias de DNA , Detecção Precoce de Câncer , Endoscopia Gastrointestinal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Curva ROC , Sensibilidade e Especificidade , Análise de Sequência de DNA , Máquina de Vetores de Suporte , Adulto Jovem
11.
J Gastroenterol Hepatol ; 32(10): 1723-1729, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28251689

RESUMO

BACKGROUND AND AIM: Multiple colorectal polyps are relevant in hereditary colorectal cancer (CRC) syndromes, which are thought to be caused by multiple events including germline mutations. This study was aimed to characterize germline mutations in Chinese patients with multiple colorectal polyps. METHODS: Patients with > 10 colorectal polyps at the Department of Gastroenterology of the PLA Army General Hospital were enrolled from January 2014 to December 2015. These patients were divided into the high-risk, moderate-risk, and mild-risk groups. White blood cell samples were collected, and DNA was extracted to sequence a panel of 19 genes previously associated with CRC by next-generation sequencing. RESULTS: A total of 96 patients were enrolled in the study. Pathogenic germline mutations were found in 24 (24/33, 72.73%), nine (9/24, 37.5%), and three patients (3/39, 7.7%) in the high-risk, moderate-risk, and mild-risk groups, respectively. Based on the results given, we suggested a strategy about gene sequencing test for the patients with multiple polyps, and the sensitivity and specificity of the screening strategy were 97% and 57%, respectively. Four of eight patients with MUTYH pathogenic germline mutations had the c.A934-2G monoallelic germline mutation, whereas three of eight patients had the C55T MUTYH germline mutation. Concurrent pathogenic germline mutations in APC and MUTYH were also observed. CONCLUSIONS: A genetic screening strategy comprising 19 genes was effective to screen for hereditary CRC syndromes in patients with multiple colorectal polyps. The MUTYH germline mutation hotspots in Chinese patients may be different from those in Caucasian patients.


Assuntos
Mutação em Linhagem Germinativa , Pólipos Intestinais/genética , Doenças Retais/genética , Proteína da Polipose Adenomatosa do Colo/genética , Adulto , Idoso , Povo Asiático/genética , China , Pólipos do Colo/genética , DNA Glicosilases/genética , Feminino , Testes Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
Toxicol Appl Pharmacol ; 292: 56-64, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26765310

RESUMO

Gossypol, a polyphenolic compound isolated from cottonseeds, has been reported to possess many pharmacological activities, but whether it can influence inflammasome activation remains unclear. In this study, we found that in mouse macrophages, gossypol induced cell death characterized by rapid membrane rupture and robust release of HMGB1 and pro-caspase-11 comparable to ATP treatment, suggesting an induction of pyroptotic cell death. Unlike ATP, gossypol induced much low levels of mature interleukin-1ß (IL-1ß) secretion from mouse peritoneal macrophages primed with LPS, although it caused pro-IL-1ß release similar to that of ATP. Consistent with this, activated caspase-1 responsible for pro-IL-1ß maturation was undetectable in gossypol-treated peritoneal macrophages. Besides, RAW 264.7 cells lacking ASC expression and caspase-1 activation also underwent pyroptotic cell death upon gossypol treatment. In further support of pyroptosis induction, both pan-caspase inhibitor and caspase-1 subfamily inhibitor, but not caspase-3 inhibitor, could sharply suppress gossypol-induced cell death. Other canonical pyroptotic inhibitors, including potassium chloride and N-acetyl-l-cysteine, could suppress ATP-induced pyroptosis but failed to inhibit or even enhanced gossypol-induced cell death, whereas nonspecific pore-formation inhibitor glycine could attenuate this process, suggesting involvement of a non-canonical pathway. Of note, gossypol treatment eliminated thioglycollate-induced macrophages in the peritoneal cavity with recruitment of other leukocytes. Moreover, gossypol administration markedly decreased the survival of mice in a bacterial sepsis model. Collectively, these results suggested that gossypol induced pyroptosis in mouse macrophages via a non-canonical inflammasome pathway, which raises a concern for its in vivo cytotoxicity to macrophages.


Assuntos
Gossipol/toxicidade , Inflamassomos/metabolismo , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Piroptose/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Linhagem Celular , Relação Dose-Resposta a Droga , Camundongos , Camundongos Endogâmicos C57BL , Piroptose/fisiologia , Transdução de Sinais/fisiologia
16.
Yao Xue Xue Bao ; 49(8): 1136-42, 2014 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-25322555

RESUMO

The effect of amygdalin joint hydroxysafflor yellow A (HSYA) on the endplate chondrocytes derived from intervertebral discs of rats induced by IL-1beta and the possible mechanism were studied and explored. Chondrocytes were obtained from endplate of one-month SD rat intervertebral discs and cultured primary endplate chondrocytes. After identification, they were divided into normal group, induced group, amygdalin group, HSYA group and combined group. CCK-8 kit was adopted to detect the proliferation of the endplate chondrocytes. FCM was measured to detect the apoptosis. Real-time PCR method was adopted to observe the mRNA expression of Aggrecan, Col 2 alpha1, Col 10 alpha1, MMP-13 and the inflammatory cytokines IL-1beta. The protein expression of Col II, Col X was tested through immunofluorescence. Compared with the normal group, the proliferation of the endplate chondrocytes decreased while the apoptosis increased (P < 0.05). With down regulation of the mRNA expressions of Aggrecan, Col 2 alpha1 and up regulation of the mRNA expressions of Col 10 alpha1, MMP-13, IL-1beta (P < 0.05), the protein expression of Col II decreased while the protein expression of Col X increased. Compared with the induced group, amygdalin group, HSYA group, the combined group could inhibit the apoptosis and promote the proliferation (P < 0.05). They could increase the mRNA expressions of Aggrecan and Col 2 alpha1 while decrease the mRNA expressions of Col 10 alpha1, MMP-13 and IL-1beta (P < 0.05). They could also enhance the protein expression of Col II while reduce the protein expression of Col X. The effect of the combined group was significantly better than that of amygdalin and HSYA. Amygdalin joint HSYA could inhibit the degeneration of the endplate chondrocytes derived from intervertebral discs of rats induced by IL-1beta and better than the single use of amygdalin or HSYA.


Assuntos
Amigdalina/farmacologia , Chalcona/análogos & derivados , Condrócitos/efeitos dos fármacos , Disco Intervertebral/citologia , Quinonas/farmacologia , Animais , Apoptose , Células Cultivadas , Chalcona/farmacologia , Colágeno/metabolismo , Sinergismo Farmacológico , Interleucina-1beta , Ratos
17.
Open Med (Wars) ; 19(1): 20230881, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38221935

RESUMO

This study aimed to compare the postoperative analgesic efficacy and motor recovery of a novel lumbar plexus block (LPB) with that of a femoral nerve block (FNB) after total knee arthroplasty (TKA). Forty patients who underwent TKA were randomised equally into an lumbar plexus and sciatic nerve (LS) group (receiving novel LPB) and an femoral and sciatic nerves (FS) group (receiving FNB). The assessed variables were the onset time of pain, time to the first analgesic request, pain scores, motor block at 6, 12, and 24 h after TKA, and the number of patients receiving successful blockade for each branch of the lumbar plexus. In the LS group, the femoral, lateral femoral cutaneous, genitofemoral, iliohypogastric, ilioinguinal, and obturator nerves were blocked in 18, 20, 16, 18, 15, and 19 patients. Compared to the FS group, the LS group had a significantly shorter onset time of pain and time to the first analgesic request, a significantly larger total postoperative dose of sufentanil, significantly higher numeric rating scale scores for both rest and dynamic pain at 6, 12, and 24 h, and faster motor recovery. Novel ultrasound-guided LPB has a high blocking success rate and provides inferior postoperative analgesia, but faster motor recovery after TKA than FNB.

18.
Front Immunol ; 15: 1450998, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39281670

RESUMO

Programmed cell death (PCD) is a fundamental biological process for maintaining cellular equilibrium and regulating development, health, and disease across all living organisms. Among the various types of PCD, apoptosis plays a pivotal role in numerous diseases, notably cancer. Cancer cells frequently develop mechanisms to evade apoptosis, increasing resistance to standard chemotherapy treatments. This resistance has prompted extensive research into alternative mechanisms of programmed cell death. One such pathway is oncosis, characterized by significant energy consumption, cell swelling, dilation of the endoplasmic reticulum, mitochondrial swelling, and nuclear chromatin aggregation. Recent research suggests that oncosis can impact conditions such as chemotherapeutic cardiotoxicity, myocardial ischemic injury, stroke, and cancer, mediated by specific oncosis-related proteins. In this review, we provide a detailed examination of the morphological and molecular features of oncosis and discuss various natural or small molecule compounds that can induce this type of cell death. Additionally, we summarize the current understanding of the molecular mechanisms underlying oncosis and its role in both normal physiology and pathological conditions. These insights aim to illuminate future research directions and propose innovative strategies for leveraging oncosis as a therapeutic tool against human diseases and cancer resistance.


Assuntos
Apoptose , Neoplasias , Humanos , Neoplasias/patologia , Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Animais , Transdução de Sinais , Morte Celular , Mitocôndrias/metabolismo
19.
World J Gastrointest Surg ; 15(7): 1286-1293, 2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37555113

RESUMO

BACKGROUND: Hepatic portal blood flow occlusion is a common technique for reducing hepatic hemorrhage during hepatectomy. We designed a novel Y-Z magnetic hepatic portal blocking band (Y-Z MHPBB) based on the principle of magnetic compression technique. AIM: To introduce the Y-Z MHPBB device and verify the feasibility of this device for hepatic portal blood flow occlusion in dogs. METHODS: Ten beagles were randomly divided into the experimental group and control group. The operation time, intraoperative blood loss, the number of portal blood flow occlusions, the total time spent on adjusting the blocking band, and the average time spent on adjusting the blocking band were recorded. The surgeons evaluated the feasibility and flexibility of the two portal occlusion devices. RESULTS: Laparoscopic hepatectomy was successfully performed in both the experimental group and control group. There was no statistical difference between the two groups in the operation time, intraoperative blood loss, and the number of hepatic portal blood flow occlusions. With respect to the total time spent on adjusting the blocking band and the average time spent on adjusting the blocking band, the experimental group showed significantly better outcomes than the control group, with a statistical difference (P < 0.05). The operators found that the Y-Z MHPBB was superior to the modified T-tube in terms of operational flexibility. CONCLUSION: The Y-Z MHPBB seems to be an ingenious design, accurate blood flow occlusion effect, and good flexibility; and it can be used for hepatic portal blood flow occlusion during laparoscopic hepatectomy.

20.
World J Gastrointest Surg ; 15(7): 1294-1303, 2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37555127

RESUMO

BACKGROUND: Magnetic compression anastomosis (MCA) is a simple procedure contributing to a reliable anastomosis. However, digestive-tract reconstruction after total gastrectomy using MCA has not yet been reported. AIM: To investigate the feasibility of MCA for simultaneous esophagojejunostomy and jejunojejunostomy after total gastrectomy using beagle dogs. METHODS: Sixteen beagles were randomly divided into an MCA group (study group, n = 8) and a manual-suture anastomosis group (control group, n = 8). Two different magnetic anastomosis devices were used in the study group for esophagojejunal and jejunojejunal anastomoses. Both devices included a pair of circular daughter and parent magnets each. The time of esophagojejunostomy and jejunojejunostomy, postoperative complications, and survival rate of the two groups were compared. The dogs were sacrificed one month after the operation and their anastomotic specimens were obtained. Healing was observed by the naked eye and a light microscope. RESULTS: Digestive-tract reconstruction after total gastrectomy was successfully completed in both groups (survival rate = 100%). In the study group, esophagojejunal and jejunojejunal anastomoses took 6.13 ± 0.58 and 4.06 ± 0.42 min, respectively, significantly lower than those in the control group (15.63 ± 1.53 min, P < 0.001 and 10.31 ± 1.07 min, P < 0.001, respectively). Complications such as bleeding, anastomotic leakage, and anastomotic stenosis were not observed. In the study group, the magnets did not interfere with each other. Discharge time of the jejunojejunal magnetic anastomosis device was 10.75 ± 1.28 d, while that of the esophagojejunal magnetic anastomosis device was 12.25 ± 1.49 d. Residual silk was found in the control group. The study group showed a greater smoothness of the anastomosis than that of the control group. All layers of anastomosis healed well in both groups. CONCLUSION: MCA is a safe and feasible procedure for digestive-tract reconstruction after total gastrectomy in this animal model.

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