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1.
BMC Cancer ; 24(1): 776, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937664

RESUMO

BACKGROUND: Primary cervical cancer screening and treating precancerous lesions are effective ways to prevent cervical cancer. However, the coverage rates of human papillomavirus (HPV) vaccines and routine screening are low in most developing countries and even some developed countries. This study aimed to explore the benefit of an artificial intelligence-assisted cytology (AI) system in a screening program for a cervical cancer high-risk population in China. METHODS: A total of 1231 liquid-based cytology (LBC) slides from women who underwent colposcopy at the Chinese PLA General Hospital from 2018 to 2020 were collected. All women had received a histological diagnosis based on the results of colposcopy and biopsy. The sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), false-positive rate (FPR), false-negative rate (FNR), overall accuracy (OA), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and Youden index (YI) of the AI, LBC, HPV, LBC + HPV, AI + LBC, AI + HPV and HPV Seq LBC screening strategies at low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) thresholds were calculated to assess their effectiveness. Receiver operating characteristic (ROC) curve analysis was conducted to assess the diagnostic values of the different screening strategies. RESULTS: The Se and Sp of the primary AI-alone strategy at the LSIL and HSIL thresholds were superior to those of the LBC + HPV cotesting strategy. Among the screening strategies, the YIs of the AI strategy at the LSIL + threshold and HSIL + threshold were the highest. At the HSIL + threshold, the AI strategy achieved the best result, with an AUC value of 0.621 (95% CI, 0.587-0.654), whereas HPV testing achieved the worst result, with an AUC value of 0.521 (95% CI, 0.484-0.559). Similarly, at the LSIL + threshold, the LBC-based strategy achieved the best result, with an AUC of 0.637 (95% CI, 0.606-0.668), whereas HPV testing achieved the worst result, with an AUC of 0.524 (95% CI, 0.491-0.557). Moreover, the AUCs of the AI and LBC strategies at this threshold were similar (0.631 and 0.637, respectively). CONCLUSIONS: These results confirmed that AI-only screening was the most authoritative method for diagnosing HSILs and LSILs, improving the accuracy of colposcopy diagnosis, and was more beneficial for patients than traditional LBC + HPV cotesting.


Assuntos
Inteligência Artificial , Detecção Precoce de Câncer , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/patologia , Adulto , Detecção Precoce de Câncer/métodos , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Colposcopia , China/epidemiologia , Sensibilidade e Especificidade , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/virologia , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/epidemiologia , Adulto Jovem , Curva ROC , Citodiagnóstico/métodos
2.
Int J Surg ; 110(5): 2902-2909, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38348866

RESUMO

BACKGROUND: Burn patients with inhalation injury are at higher risk of developing pneumonia, and yet there is no reliable tool for the assessment of the risk for such patients at admission. This study aims to establish a predictive model for pneumonia risk for burn patients with inhalation injury based on clinical findings and laboratory tests. METHOD: This retrospective study enrolled 546 burn patients with inhalation injury. They were grouped into a training cohort and a validation cohort. The least absolute shrinkage and selection operator (LASSO) regression analysis and binary logistic regression analysis were utilized to identify risk factors for pneumonia. Based on the factors, a nomogram for predicting pneumonia in burn patients with inhalation injury was constructed. Areas under the receiver operating characteristic curves (AUC), calibration plots, and decision curve analysis (DCA) were used to evaluate the efficiency of the nomogram in both the training and validation cohorts. RESULTS: The training cohort included 432 patients, and the validation cohort included 114 patients, with a total of 225 (41.2%) patients experiencing pneumonia. Inhalation injury, tracheal intubation/tracheostomy, low serum albumin, and high blood glucose were independent risk factors for pneumonia in burn patients with inhalation injury and they were further used to build the nomogram. The AUC of the nomogram in the training and validation cohorts were 0.938 (95% CI: 0.917-0.960) and 0.966 (95% CI: 0.931-1), respectively. The calibration curve for probability of pneumonia showed optimal agreement between the prediction by nomogram and the actual observation, and the DCA indicated that the constructed nomogram conferred high clinical net benefit. CONCLUSION: This nomogram can accurately predict the risk of developing pneumonia for burn patients with inhalation injury, and help professionals to identify high-risk patients at an early stage as well as to make informed clinical decisions.


Assuntos
Queimaduras , Nomogramas , Pneumonia , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pneumonia/diagnóstico , Pneumonia/etiologia , Pneumonia/epidemiologia , Pessoa de Meia-Idade , Adulto , Fatores de Risco , Queimaduras/complicações , Medição de Risco , Curva ROC
3.
Int Wound J ; 20(9): 3457-3466, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37269235

RESUMO

Deep sternal wound infection (DSWI) is a relatively complex wound in wound reconstruction surgery. Because plastic surgeons deal with DSWI patients late. The primary healing (healing by first intention) after reconstruction of DSWI is restricted by many preoperative risk factors. The purpose of this study is to explore and analyse the risk factors of primary healing failure in patients with DSWI treated with platelet-rich plasma (PRP) and negative pressure trauma therapy (NPWT). 115 DSWI patients treated with the PRP and NPWT (PRP + NPWT) modality were retrospectively (2013-2021) analysed. They were divided into two groups according to primary healing results after the first PRP + NPWT treatment. Univariate and multivariate analyses were used to compare the data of the two groups to find out the risk factors and their optimal cut-off values were identified by ROC analysis. The primary healing results, debridement history, wound size, sinus, osteomyelitis, renal function, bacterial culture, albumin (ALB), platelet (PLT) between the two groups were significantly different (P < 0.05). Binary logistic regression showed that osteomyelitis, sinus, ALB and PLT were the risk factors affecting primary healing outcomes (P < 0.05). ROC analysis showed that AUC for ALB in the non-primary healing group was 0.743 (95% CI: 0.650-0.836, P < 0.05) and its optimal cutoff value of 31 g/L was associated with primary healing failure with a sensitivity of 96.9% and specificity of 45.1%. AUC for PLT in the non-primary healing group was 0.670 (95% CI: 0.571 ~ 0.770, P < 0.05) its optimal cutoff value of 293 × 109 /L was associated with primary healing failure with a sensitivity of 72.5% and specificity of 56.3%. In the cases included in this study, the success rate of primary healing of DSWI treated with PRP + NPWT was not affected by the most common preoperative risk factors for wound non-union. It is indirectly confirmed that PRP + NPWT is an ideal treatment. However, it should be noted that it will still be adversely affected by sinus osteomyelitis, ALB and PLT. The patients need to be carefully evaluated and corrected before reconstruction.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Tratamento de Ferimentos com Pressão Negativa , Osteomielite , Plasma Rico em Plaquetas , Humanos , Esternotomia/efeitos adversos , Infecção da Ferida Cirúrgica/terapia , Infecção da Ferida Cirúrgica/etiologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Fatores de Risco , Osteomielite/cirurgia , Osteomielite/complicações , Tratamento de Ferimentos com Pressão Negativa/métodos
4.
J Trauma Acute Care Surg ; 95(4): 549-557, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37314424

RESUMO

BACKGROUND: Delayed resuscitation (DR) can induce hepatic reperfusion injury after severe burns. The underlying molecular mechanisms of DR-induced hepatic injury remain unidentified. This study sought to predict candidate genes and molecular pathways in a DR-induced hepatic injury preclinical model. METHODS: Rats were randomized into three groups: the sham injury (Sham) group; the DR group, which had third-degree burns covering 30% of the body surface area and DR; and the early resuscitation (ER) group, in which ER was administered. The liver tissue was harvested for the purpose of evaluating hepatic injury and performing transcriptome sequencing. Differentially expressed genes (DEGs) for DR versus Sham and ER versus DR were analyzed respectively. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Ingenuity Pathway Analysis were used. The DEGs and critical module genes were intersected to obtain critical genes. Immune infiltration and competing endogenous RNA networks were also analyzed. Validation was conducted using quantitative real-time polymerase chain reaction. RESULTS: Hepatic injury was evident in DR rats. There were 2,430 DEGs between DR and Sham and 261 DEGs between ER and DR. Differentially expressed genes were mostly enriched in metabolic process for DR versus Sham, and immune and inflammatory processes for ER versus DR. Four critical genes (Tff3, C1galt1, Cd48, and MGC105649) were obtained by screening. Five immune cells were significantly different between DR and Sham, and seven immune cells were significantly different between ER and DR in immunoassays. Three critical genes, 75 miRNAs, 7 lncRNAs, and 197 edges constituted the mRNA-miRNA-lncRNA linkages, which included C1galt1-rno-miR-330-5p-Pvt1, among others. CONCLUSION: This is the first attempt to perform a high-throughput analysis of gene expression profiles in DR-induced hepatic injury. It shows that immunity and inflammation-related RNAs and pathways play an important role in the progression of hepatic injury. It also provides insight into some important RNAs and regulatory targets related to disease.


Assuntos
Queimaduras , MicroRNAs , Ratos , Animais , Perfilação da Expressão Gênica , Fígado/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Transcriptoma , Queimaduras/complicações , Queimaduras/genética , Queimaduras/terapia
5.
J Agric Food Chem ; 71(20): 7858-7865, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37163296

RESUMO

LsSAT2 (serine acetyltransferase in Lathyrus sativus) is the rate-limiting enzyme in biosynthesis of ß-N-oxalyl-l-α,ß-diaminopropionic acid (ß-ODAP), a neuroactive metabolite distributed widely in several plant species including Panax notoginseng, Panax ginseng, and L. sativus. The enzymatic activity of LsSAT2 is post-translationally regulated by its involvement in the cysteine regulatory complex in mitochondria via interaction with ß-CAS (ß-cyanoalanine synthase). In this study, the binding sites of LsSAT2 with the substrate Ser were first determined as Glu290, Arg316, and His317 and the catalytic sites were determined as Asp267, Asp281, and His282 via site-directed/truncated mutagenesis, in vitro enzymatic activity assay, and functional complementation of the SAT-deficient Escherichia coli strain JM39. Furthermore, the C-terminal 10-residue peptide of LsSAT2 is confirmed to be critical to interact with LsCAS, and Ile336 in C10 peptide is the critical amino acid. These results will enhance our understanding of the regulation of LsSAT2 activities and the biosynthesis of ß-ODAP in L. sativus.


Assuntos
Diamino Aminoácidos , Lathyrus , Lathyrus/química , Serina O-Acetiltransferase/metabolismo , Aminoácidos/metabolismo
6.
J Cardiothorac Surg ; 18(1): 184, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37208736

RESUMO

Sternal wound infection (SWI) is the most common complication of the median sternal incision. The treatment time is long, and the reconstruction is difficult, which causes challenges for surgeons. Plastic surgeons were often involved too late in such clinical scenarios when previous empirical treatments failed and the wound damage was relatively serious. Accurate diagnosis and risk factors against sternal wound infection need to be in focus. Classification of different types of sternotomy complications post-cardiac surgery is important for specific categorization and management. Not familiar with this kind of special and complex wound, objectively increasing the difficulty of wound reconstruction. The purpose of this comprehensive review is to review the literature, introduce various SWI risk factors related to wound nonunion, various classification characteristics, advantages and disadvantages of various wound reconstruction strategies, to help clinicians understand the pathophysiological characteristics of the disease and choose a better treatment method.


Assuntos
Procedimentos de Cirurgia Plástica , Retalhos Cirúrgicos , Humanos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/terapia , Infecção da Ferida Cirúrgica/etiologia , Esterno/cirurgia , Esternotomia/efeitos adversos , Fatores de Risco , Estudos Retrospectivos
7.
Int Wound J ; 20(6): 2241-2249, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36802113

RESUMO

Pilonidal sinus disease (PNSD) challenged surgeons for decades. Limberg flap repair (LFR) is a common treatment for PNSD. The purpose of this study was to observe the effect and risk factors of LFR in PNSD. A retrospective study was conducted on the PNSD patients who visited two medical centers and four departments in the People's Liberation Army General Hospital and were taking LFR treatment between 2016 and 2022. The risk factors, the effect of the operation, and complications were observed. The effects of known risk factors on the surgical results were compared. There were 37 PNSD patients: male/female ratio of 35:2, average age: 25.1 ± 7.9 years. Average BMI: 25.2 ± 4.0 kg/m2 , average wound healing time: 15.4 ± 3.4 days. 30 patients (81.0%) healed in stage one and 7 (16.3%) had postoperative complications. Only 1 patient (2.7%) had a recurrence while others were healed after dressing-changing. There was no significant difference in age, BMI, preoperative debridement history, preoperative sinus classification, Wound area, Negative pressure drainage tube, prone time (<3d) and treatment effect. Squat defecate and premature defecation were associated with treatment effect, and they were independent predictors of treatment effect in the multivariate analysis. LFR has a stable therapeutic outcome. Compared with other skin flaps, the therapeutic effect of this flap is not significantly different, but the design is simple and is not affected by the known risk factors before operation. However, it is necessary to avoid the influence of two independent risk factors, squatting defecation and premature defecation, on the therapeutic effect.


Assuntos
Seio Pilonidal , Procedimentos de Cirurgia Plástica , Dermatopatias , Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Estudos Retrospectivos , Seio Pilonidal/cirurgia , Recidiva Local de Neoplasia/cirurgia , Retalhos Cirúrgicos/cirurgia , Dermatopatias/cirurgia , Recidiva , Resultado do Tratamento
8.
Int Wound J ; 20(6): 1911-1920, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36575064

RESUMO

Pressure injury often seriously affects the life quality of aged patients, especially the long-term bedridden casualties. Widely adopted by different disciplines, negative pressure suction has its role in pressure injury. Microskin implantation has been demonstrated powerful in increasing the expansion ratio of donor area-derived skin and accelerating wound healing by forming "skin islands". The study was designed to evaluate the efficacy and safety of additional use of bedside microskin implantation in the palliative care of pressure injury of aged patients who cannot tolerate surgical treatment as a supplement for standard negative pressure suction. An open-label within-patient RCT was conducted in aged patients with pressure injury. Sixteen patients were enrolled. After granulation tissues formed, half of a pressure injury was randomised to receive the negative pressure suction as the control group, and the other half exposed to additional bedside microskin implantation as the experimental group. Efficacy was evaluated within 1 month after treatment, and the primary endpoints included the wound healing rate and pressure ulcer scale for healing (PUSH) scores. The secondary outcomes included survival rate of implanted microskin, pain intensity assessment, satisfaction surveys from patients or their family, and pressure ulcer healing complications. Sixteen patients completed the study. After 14 days of operation, 5.63 ± 1.78 out of 10 pieces of implanted microskin survived and formed neonatal epithelium. The wound healing rates of the control group and the experimental group at 1 month were (26.17 ± 9.03%) and (35.95 ± 16.02%), respectively (P < .01). The mean PUSH score before the surgery was 12.38 ± 2.23. At 1 month after surgery, the mean difference of PUSH score from baseline was 2.13 ± 0.96 in the control group and 2.81 ± 0.83 in the experimental group (P < .01). The treatment of microskin implantation did not cause additional pain or complications to the patients. Accompanied by a better ulcer status, the majority of patients or their guardians have a high degree of acceptance towards the microskin implantation. Bedside microskin implantation could accelerate wound healing with lower PUSH scores. As a complementary palliative treatment, supplementary microskin implantation is effective and well tolerated.


Assuntos
Úlcera por Pressão , Idoso , Humanos , Úlcera por Pressão/cirurgia , Pele/lesões , Transplante de Pele , Transplante Autólogo , Cicatrização
9.
J Trauma Acute Care Surg ; 93(5): 712-718, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36301128

RESUMO

BACKGROUND: Severely burned patients have a higher risk of diabetes mellitus after healing, but its mechanism remains unclear. Therefore, the purpose of the study was to explore the influence of burns on pancreatic islets of mice after wound healing. METHODS: Forty-two male C57BL/6 mice were randomized into a sham group and a burn group and subjected to sham treatment or a third-degree burn model of 30% total body surface area. Fasting blood glucose was detected weekly for 8 weeks after severe burns. Glucose-stimulated insulin secretion was measured 8 weeks post severe burns. Islets of the two groups were isolated and mRNA libraries were sequenced by the Illumina sequencing platform. The expressions of differentially expressed genes (DEGs) related to the cell cycle and the amounts of mitochondrial DNA were detected by quantitative real-time polymerase chain reaction after gene ontology, gene set enrichment analysis, and protein-protein network analysis. Hematoxylin-eosin staining of pancreatic tail tissue and adenosine triphosphate (ATP) assay of islets were performed. RESULTS: The levels of fasting blood glucose were significantly higher within 8 weeks post severe burns. Glucose-stimulated insulin secretion was impaired at the eighth week post severe burns. Totally 128 DEGs were selected. Gene ontology and gene set enrichment analysis indicated that the pathways related to the cell cycle, protein processing, and oxidative phosphorylation were downregulated. The expressions of DEGs related to the cell cycle showed a consistent trend with mRNA sequencing data, and most of them were downregulated post severe burns. The cell mass of the burn group was less than that of the sham group. Also, the concentration of ATP and the amount of mitochondrial DNA were lower in the burn group. CONCLUSION: In the model of severe-burned mice, disorders in glucose metabolism persist for 8 weeks after burns, which may be related to low islet cell proliferation, downregulation of protein processing, and less ATP production.


Assuntos
Queimaduras , Ilhotas Pancreáticas , Animais , Masculino , Camundongos , Trifosfato de Adenosina/metabolismo , Glicemia , Queimaduras/genética , Queimaduras/metabolismo , DNA Mitocondrial/metabolismo , Glucose/metabolismo , Camundongos Endogâmicos C57BL , RNA Mensageiro/metabolismo , Transcriptoma , Cicatrização/genética
10.
Polymers (Basel) ; 14(13)2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35808568

RESUMO

The zeolitic imidazolate framework (ZIF-8)@polyacrylonitrile (PAN) nanofiber membrane was prepared and carbonized for heavy metal cadmium ion (Cd2+) adsorption in aqueous medium. Zinc oxide (ZnO) was first sputtered onto the surface of the PAN electrospun nanofiber membrane to provide a metal ion source. Then, the ZIF-8@PAN nanofiber membrane was prepared via in situ solvothermal reaction and carbonized in a tube furnace at 900 °C under a N2 atmosphere to enhance adsorption performance. The synthesized ZIF-8 particles with polyhedral structure were uniformly immobilized on the surface of the PAN electrospun nanofiber membrane. After being heated at 900 °C, the polygonal ZIF-8 shrank, and the carbonized ZIF-8@PAN nanofiber membrane was obtained. Compared with the nanofiber membrane without being carbonized, the adsorption capacity of the carbonized ZIF-8@PAN nanofiber membrane reached 102 mg L-1, and its Cd2+ adsorption efficiency could be more than 90% under the adsorption temperature of 35 °C and solution of pH = 7.5 conditions. According to the adsorption thermodynamics analysis, the Cd2+ adsorption process of the carbonized ZIF-8@PAN nanofiber membrane was spontaneous. The whole Cd2+ adsorption process was more suitably described by the pseudo second-order adsorption kinetics model, indicating that there exists a chemical adsorption mechanism besides physical adsorption.

11.
Front Cell Dev Biol ; 10: 1075810, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36589750

RESUMO

We present the use of conductive spray polymer ionization mass spectrometry (CPSI-MS) combined with machine learning (ML) to rapidly gain the metabolic fingerprint from 1 µl liquid extraction from the biopsied tissue of triple-negative breast cancer (TNBC) in China. The 76 discriminative metabolite markers are verified at the primary carcinoma site and can also be successfully tracked in the serum. The Lasso classifier featured with 15- and 22-metabolites detected by CPSI-MS achieve a sensitivity of 88.8% for rapid serum screening and a specificity of 91.1% for tissue diagnosis, respectively. Finally, the expression levels of their corresponding upstream enzymes and transporters have been initially confirmed. In general, CPSI-MS/ML serves as a cost-effective tool for the rapid screening, diagnosis, and precise characterization for the TNBC metabolism reprogramming in the clinical practice.

12.
J Med Chem ; 64(11): 7434-7452, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34011155

RESUMO

BCR-ABL kinase inhibition is an effective strategy for the treatment of chronic myeloid leukemia (CML). Herein, we report compound 3a-P1, bearing a difluoro-indene scaffold, as a novel potent pan-inhibitor against BCR-ABL mutants, including the most refractory T315I mutant. As the privileged (S)-isomer compared to its (R)-isomer 3a-P2, 3a-P1 exhibited potent antiproliferative activities against K562 and Ku812 CML cells and BCR-ABL and BCR-ABLT315I BaF3 cells, with IC50 values of 0.4, 0.1, 2.1, and 4.7 nM, respectively. 3a-P1 displayed a good safety profile in a battery of assays, including single-dose toxicity, hERG K+, and genotoxicity. It also showed favorable mice pharmacokinetic properties with a good oral bioavailability (32%), a reasonable half-life (4.61 h), and a high exposure (1386 h·ng/mL). Importantly, 3a-P1 demonstrated a higher potency than ponatinib in a mice xenograft model of BaF3 harboring BCR-ABLT315I. Overall, the results indicate that 3a-P1 is a promising drug candidate for the treatment of CML to overcome the imatinib-resistant T315I BCR-ABL mutation.


Assuntos
Desenho de Fármacos , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Piperazina/química , Inibidores de Proteínas Quinases/química , Administração Oral , Animais , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas de Fusão bcr-abl/metabolismo , Meia-Vida , Humanos , Imidazóis/química , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Isomerismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Camundongos , Camundongos Endogâmicos ICR , Simulação de Acoplamento Molecular , Mutação , Piperazina/metabolismo , Piperazina/farmacologia , Piperazina/uso terapêutico , Inibidores de Proteínas Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Piridazinas/química , Piridazinas/farmacologia , Piridazinas/uso terapêutico , Relação Estrutura-Atividade
13.
J Agric Food Chem ; 69(6): 1953-1962, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33538593

RESUMO

ß-N-Oxalyl-l-α,ß-diaminopropionic acid (ß-ODAP), found in Lathyrus sativus at first, causes a neurological disease, lathyrism, when over ingested in an unbalanced diet. Our previous research suggested that ß-ODAP biosynthesis is related to sulfur metabolism. In this study, ß-cyanoalanine synthase (ß-CAS) was confirmed to be responsible for ß-ODAP biosynthesis via in vitro enzymatic analysis. LsCAS was found to be pyridoxal phosphate (PLP)-dependent via spectroscopic analysis and dual functional via enzymatic activity analysis. Generation of a M135T/M235S/S239T triple mutant of LsCAS, which are the key sites to control the ratio of CAS/cysteine synthase (CS) activity, switches reaction chemistry to that of a CS. LsCAS interactions were further screened and verified via Y2H, BiFC and pull-down assay. It was suggested that LsSAT2 interacts and forms a cysteine regulatory complex (CRC) with LsCAS in mitochondria, which improves LsSAT while reduces LsCAS activities to affect ß-ODAP content positively. These results provide new insights into the molecular regulation of ß-ODAP content in L. sativus.


Assuntos
Diamino Aminoácidos , Lathyrus , Lathyrus/genética , Liases , Serina O-Acetiltransferase
14.
Oncogene ; 39(13): 2707-2723, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32005973

RESUMO

Mitochondrial fusion and fission dynamics fine-tune cellular calcium homeostasis, ATP production capacity and ROS production and play important roles in cell proliferation and migration. Dysregulated mitochondrial dynamics is closely related to tumor development, but the mechanism of mitochondrial dynamics dysregulation and its role in the development of lung cancer remains unclear. Here, we demonstrate that the DNA sensor protein absent in melanoma 2 (AIM2) is highly expressed in non-small cell lung cancer (NSCLC) cells and that high AIM2 expression is associated with poor prognosis in patients with NSCLC. High expression of AIM2 contributes to tumor cell growth and proliferation independent of inflammasome activation in vitro and in vivo. Further studies have shown that AIM2 colocalizes with mitochondria in NSCLC cells and that AIM2 knockdown leads to enhanced mitochondrial fusion and decreased cell proliferation. Mechanistic studies have shown that AIM2 downregulation promotes MFN2 upregulation, thereby enhancing mitochondrial fusion. Moreover, we found that mitochondrial fusion driven by AIM2 knockdown leads to a decrease of cellular reactive oxygen species (ROS) production, which further causes inactivation of the MAPK/ERK signaling pathway. Together, we discovered a novel function of AIM2 in promoting NSCLC development by regulating mitochondrial dynamics and revealed its underlying mechanism. Our work provides new intervention targets for the treatment of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas de Ligação a DNA/metabolismo , Neoplasias Pulmonares/genética , Mitocôndrias/patologia , Dinâmica Mitocondrial/genética , Animais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Proteínas de Ligação a DNA/genética , Conjuntos de Dados como Assunto , Feminino , GTP Fosfo-Hidrolases/metabolismo , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Sistema de Sinalização das MAP Quinases/genética , Camundongos , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Prognóstico , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Artigo em Chinês | MEDLINE | ID: mdl-31245951

RESUMO

OBJECTIVE: To investigate the protective effects of shen-mai injection on intestinal barrier function in the early stage of 30% 3° scald, and to provide experimental basis for the prevention and control of enterogenic infection. METHODS: A total of 60 Wistar rats were randomly divided into 6 groups: normal control group (without treatment), model control group (with 30% total body surface area (TBSA) fully thickness burn on the back), hexadecadrol (5 mg/kg) group, Shenmai injection (5, 10, 15 mg/kg) groups, with 10 rats in each group. After burned by scald apparatus, rats in each group were treated with drugs immediately by intraperitoneal injection once a day. At 72 hours after burned, the levels of plasma endotoxin, diamine oxidase (DAO), tumor necrosis factor-alpha (TNF-α), interleukins-6(IL-6) in all rats were detected and the mesenteric lymph nodes, liver and spleen were homogenized to culture for bacteria. The change of secretory immunoglobulin A (sIgA) in intestinal mucosa was measured. RESULTS: Compared with normal control group, bacterial translocation quantity in mesenteric lymph nodes(MLN), liver, and spleen, and the plasma levels of DAO, endotoxin, TNF-α, IL-6 and the level of sIgA in intestinal mucosa in model control group were increased significantly (P<0.01); compared with model control group, bacterial translocation quantity in MLN, liver, and spleen, and the plasma levels of DAO, endotoxin, TNF-α, IL-6 and the level of sIgA in intestinal mucosa in hexadecadrol (5 mg/kg) group and shen-mai injection (5, 10, 15 mg/kg) groups were decreased significantly (P<0.05 or P<0.01). CONCLUSION: Shen-mai injection can alleviate intestinal mucosa injury caused by severe scald, and the effects are similar with those of dexamethasone, and the effect is better in the high-dose group.


Assuntos
Queimaduras , Medicamentos de Ervas Chinesas , Mucosa Intestinal , Animais , Translocação Bacteriana/efeitos dos fármacos , Queimaduras/complicações , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Distribuição Aleatória , Ratos , Ratos Wistar
16.
Biochem Biophys Res Commun ; 489(2): 123-129, 2017 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-28536075

RESUMO

Coilin is a marker protein of the Cajal body (CB). Cajal bodies, functional nuclear structure, play important roles for the maturation of telomerase mRNAs. However, whether CB participates in the process of cell senescence is unknown. Cisplatin is a frequently used drug for the chemotherapy for various cancers, which was recently reported to be able to induce premature senescence of tumor cells. In this study, we found that when HeLa cells were treated with 2 µg/ml cisplatin for 4 days, stagnant cell growth, especially in cells stained positive of SA-ß-gal, was accompanied with significant changes in CB morphologies. The removal of cisplatin allowed the recovery of normal CB appearance, but was not able to restore cells from senescent states. Knocking down coilin expression by siRNA attenuated the growth and reduced the viability of treated cells, and the decreased rate of CB formation correlated with increased staining of SA-ß-gal. Interestingly, when coilin knocked-down cells exposed to cisplatin, the drug sensitivity as shown by the reduction of cell viability was significantly increased compared to the control siRNA transfection groups. Overexpression of coilin phosphomutants increased SA-ß-gal fluorescence following treatments with cisplatin as compared to the wild type coilin transfection. Our results indicated that coilin was an important functional player that involved in cisplatin-induced premature cell senescence. It suggested that the modulation of coilin expression could be considered as a potential anti-tumor strategy to increase the sensitivity of chemotherapy through which drug-induced cell senescence was accelerated.


Assuntos
Antineoplásicos/farmacologia , Senescência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Proteínas Nucleares/biossíntese , Antineoplásicos/química , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proliferação de Células/efeitos dos fármacos , Cisplatino/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas
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