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1.
Braz. j. biol ; 84: e246460, 2024. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1350310

RESUMO

Abstract Field survey study was conducted season (2017). Soybeans and weeds were weekly sampled randomly. Thrips adults were identified and counted. Detection of the virus isolate and the natural incidence was determined using; Mechanical transmission, host range, DAS-ELISA, RT-PCR. The natural incidence thrips individuals was detected depending on the SVNV% in thrips individuals and weeds hosts. Ten thrips species were associated with soybean plants in the field. The most abundant species was T. tabaci, average 256.5 average no.of individuals, followed by F. occidentalis (142.5 average no. of individuals), then N. variabilis (86.6/ average no. of individuals). Fourteen thrips species occurred on 5 legumes field crops and 41 weed plant species within soybean field. The highest average number 40.6.of individuals were recorded on Ammi majus. While the lowest one 3.3 average no. of individuals were on Urtica urens. Only 21diagnostic plant species were susceptible to infection with SVNV. G. max and Vigna radiate, were the highest percentage of infection 80% followed by V. unguilata & N. benthamiana, 75%. Egyptian isolate of Soybean vein necrosis virus (SVNV) in this study showed a high degree of similarity and it is closely related to TSWV from Egypt (DQ479968) and TCSV from USA (KY820965) with nucleotide sequence identity of 78%. Four thrips species transmitted SVNV (F. fusca 4.0%, F. schultzei 4.3%, F. tritici 3.3% and N. variabilis 68.0% transmission). Both C. phaseoli and M. sjostedti can acquire the virus but unable to transmit it. The following species; T. tabaci, F. occidentalis, S. dorsallis and T. palmi cannot acquire or transmit SVNV. The incidence of SVNV in the field started by the end of July then increased gradualy from 12.7 to 71.3% by the end of the season. In conclusion, few thrips individuals invaded soybean crops are enough to transmit high rate of SVNV within the crop. Furthermore, several vector species are also abundant on weeds, which are the major sources of soybean viruses transmitted to the crops. This information might be important for control and reduce the incidence of SVNV infection.


Resumo O estudo de pesquisa de campo foi realizado na temporada (2017). A soja e as ervas daninhas foram amostradas semanalmente de forma aleatória. Tripes adultos foram identificados e contados. A detecção do vírus isolado e a incidência natural foram determinadas usando transmissão mecânica, gama de hospedeiros, DAS-ELISA, RT-PCR. A incidência natural de tripes em indivíduos foi detectada dependendo da % de SVNV em tripes e hospedeiros infestantes. Dez espécies de tripes foram associadas a plantas de soja no campo. A espécie mais abundante foi T. tabaci, com média de 256,5 número médio de indivíduos, seguida por F. occidentalis (142,5) e N. variabilis (86,6 / número médio de indivíduos). Catorze espécies de tripes ocorreram em 5 culturas de leguminosas e 41 espécies de plantas daninhas dentro de campos de soja. O maior número médio de 40,6 indivíduos foi registrado em Ammi majus. Enquanto o mais baixo, 3,3 número médio de indivíduos, foi no Urtica urens. Apenas 21 espécies de plantas diagnosticadas foram suscetíveis à infecção com SVNV. G. max e Vigna radiate foram os maiores percentuais de infecção, 80%, seguidos por V. unguilata e N. benthamiana, 75%. O isolado egípcio neste estudo mostrou um alto grau de similaridade e está intimamente relacionado ao TSWV do Egito (DQ479968) e ao TCSV dos EUA (KY820965), com identidade de sequência de nucleotídeos de 78%. Quatro espécies de tripes transmitiram SVNV (F. fusca 4,0%, F. schultzei 4,3%, F. tritici 3,3% e N. variabilis 68,0% de transmissão). Tanto C. phaseoli quanto M. sjostedti podem adquirir o vírus, mas não podem transmiti-lo. As seguintes espécies, T. tabaci, F. occidentalis, S. dorsallis e T. palmi não podem adquirir ou transmitir SVNV. A incidência de SVNV no campo, iniciada no final de julho, aumentou gradativamente de 12,7 para 71,3% no final da temporada. Em conclusão, poucos indivíduos de tripes invadiram a cultura da soja e são suficientes para transmitir alta taxa de SVNV dentro da cultura. Além disso, várias espécies de vetores também abundam em ervas daninhas, que são as principais fontes dos vírus da soja transmitidos às lavouras. Essas informações podem ser importantes para controlar e reduzir a incidência de infecção por SVNV.


Assuntos
Humanos , Tospovirus , Doenças das Plantas , Soja , Incidência , Urticaceae , Egito/epidemiologia , Plantas Daninhas , Necrose
2.
Methods Mol Biol ; 2519: 53-63, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36066709

RESUMO

Many apoptosis assays are available since there are many proteins regulated at multiple points and involved in apoptosis signaling cascade. To detect apoptosis accurately, two or more assays should be used since there are many overlapped features between apoptosis and necrosis. There are six major groups of available assays to detect apoptosis: membrane alteration, mitochondrial assays, cytomorphological alterations, DNA fragmentation, detection of caspase, cleaved substrate, inhibitors and regulators, and detection of apoptosis in whole mounts. Among those assay, early apoptosis could be detected through annexin V, which is based on the loss of the cellular membrane integrity. Also, there are many assays that can detect midphase of apoptosis using caspase activation and molecular processing including PARP degradation. Late phase of apoptosis could be detected with DNA fragmentation assays. Combinations of these assays allow us to identify the mechanisms of apoptosis induction after specific stimulus. This chapter will introduce three apoptosis detection assays including annexin assay, DNA/chromatin condensation assays, and TUNEL assay.


Assuntos
Apoptose , Caspases , Anexina A5/metabolismo , Caspases/metabolismo , Fragmentação do DNA , Humanos , Necrose
3.
Methods Mol Biol ; 2543: 1-11, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36087254

RESUMO

This chapter describes a simple, nondestructive, annexin V apoptosis detection method that can be employed in real time over a 48-h test exposure. The real-time functionality allows for temporal resolution of apoptotic and cell death responses during the test exposure and obviates the need for onerous sample preparation and time course protocols associated with other annexin V methods. Further, this technique is eminently accessible to a wide range of laboratories because it does not require flow cytometry or other cytometric methods. It was developed for use with a variety of microplate well densities and with standard multimodal plate readers. The central feature of this assay is that it continuously reports the residency status of phosphatidylserine (PS) on the exofacial surface of a cell as it is translocated from the inner membrane leaflet during the apoptotic process. This homogenous, no-wash assay is made possible by two optimized and distinct annexin V fusion proteins which contain complementing NanoBiT™ luciferase enzyme subunits, a time-released luciferase substrate, and a fluorescent membrane integrity reagent. During an apoptotic event, the luminescent signal arising from an assay well is proportional to the number of cells with PS exposure, and fluorescence intensity correlates with the degree of cell death (secondary necrosis). Conversely, untreated cells contribute negligible luminescent or fluorescent signals throughout the time course. The data collected from these assay measures provide for both standard potency determinations and kinetic characterization of dose- and agent-dependent apoptotic responses, from early through late phases.


Assuntos
Apoptose , Fosfatidilserinas , Anexina A5/metabolismo , Apoptose/fisiologia , Corantes , Citometria de Fluxo/métodos , Humanos , Necrose , Fosfatidilserinas/metabolismo
4.
Methods Mol Biol ; 2543: 45-55, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36087258

RESUMO

Apoptotic cells are cleared from the body principally through recognition and engulfment by neighboring phagocytes, a process known as efferocytosis. During efferocytosis, phagocytes are recruited to the site/activated by "find me" signals released from apoptotic cells, precisely identify apoptotic cells by the recognition of "eat me" signals on the apoptotic cell surface, and engulf the apoptotic cells to prevent secondary necrosis and inflammation. Thus, efferocytosis is critical for tissue homeostasis in normal physiology. However, efferocytosis of apoptotic tumor cells-performed by tumor-associated macrophages-suppresses immunity within the tumor microenvironment and limits the antitumor response. This phenomenon is further exacerbated in tumor residual disease because of the high apoptotic cell burden generated by cytotoxic therapies. Blocking efferocytosis could be a powerful approach to boost tumor immunogenicity, particularly as a combination approach with cytotoxic therapies that produce many apoptotic cells, but little is currently known about the immune response to efferocytosis. Moreover, there is a dearth of in vivo models available to study the immunologic and therapeutic consequences of blocking efferocytosis in tumor residual disease.Here, we describe a model that enables in vivo studies of tumor immunology in the aftermath of cytotoxic therapy with an emphasis on the impact of efferocytosis. Orthotopic HER2+ mammary tumors are established in immune-competent mice, followed by a single administration of lapatinib, a receptor tyrosine kinase inhibitor of HER2, to the mice that induces widespread, transient apoptosis in the tumor microenvironment. In the days following lapatinib treatment, agents that block efferocytosis such as BMS-777607 are administered. Tissue is collected from cohorts of mice at day 2 (after lapatinib treatment only) to assess apoptosis, day 8 (after lapatinib treatment followed by blockade of efferocytosis) to assess the immune response to apoptosis and efferocytosis, and day 28 (after 4 consecutive weeks of treatment) to assess therapeutic efficacy. This model enables mechanistic studies of tumor immunology in residual disease as well as therapeutic efficacy studies of targeted agents that disrupt efferocytosis.


Assuntos
Macrófagos , Neoplasias , Animais , Apoptose/fisiologia , Lapatinib/farmacologia , Macrófagos/metabolismo , Camundongos , Necrose/patologia , Neoplasias/patologia , Fagocitose , Microambiente Tumoral
5.
Methods Mol Biol ; 2543: 57-69, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36087259

RESUMO

Apoptosis and necrosis are the two sides of the cell death penumbra. Apoptosis is a well-studied model of cell death wherein the cell destroys itself employing a predefined form of active signaling without the release of soluble cytoplasmic contents to the external environment. Compared to apoptosis, necrosis is a nonspecific form of sudden cell death in response to an invasive external stimulus which in turn is devoid of active programmed intracellular signaling leading to the sudden release of the soluble cellular contents consequent to the rupture of the cell membrane. This fundamental difference between apoptosis and necrosis made us believe that the former is the safe form of cell death and the latter is an undesirable one which often elicits an inflammatory response to the adjacent cells. Recent studies have shown that necrosis also involves a few defined cellular and complex biochemical events similar to apoptosis rendering it difficult to distinguish these two events at the single-cell level using the currently used popular assays.Here we provide a newly described detailed methodology encompassing cell system development along with a multiparametric flow cytometry-based approach to discriminate apoptotic cells from necrotic cells using a stable cell line expressing genetically encoded probe for detecting caspase activation and DsRed targeted at the mitochondria.


Assuntos
Apoptose , Mitocôndrias , Apoptose/fisiologia , Morte Celular , Citometria de Fluxo/métodos , Humanos , Mitocôndrias/metabolismo , Necrose/metabolismo
6.
Med Sci Monit ; 28: e937051, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36110037

RESUMO

Myocardial injury and necrosis caused by hyperlipidemia have been investigated by several researchers. Their pathogenesis and molecular basis are different from those of the more common clinical ischemic myocardial injury. Hyperlipidemia leads to peroxide accumulation in the cardiomyocytes, causes lipid overload, decreases the antioxidant capacity of the body, and promotes the inflammatory response. Furthermore, hyperlipidemia causes changes in the structure and function of mitochondria in the cardiomyocytes, which results in their injury and necrosis. Many previous studies have shown that metabolic diseases (eg, obesity and diabetes) and chemical poisoning can lead to hyperlipidemic myocardial injury and necrosis. Moreover, it has been observed that this pathological process can be inhibited by many small molecular substances. In the clinic, myocardial damage can be prevented or reduced by lowering the levels of triglyceride and cholesterol. Myocardial damage can also be regulated via the molecular pathway of myocardial injury caused by hyperlipidemia so that the disease can be treated. The present article reviewed the recent findings reported on the mechanisms of myocardial damage due to hyperlipidemia.


Assuntos
Hiperlipidemias , Antioxidantes/uso terapêutico , Humanos , Hiperlipidemias/tratamento farmacológico , Lipídeos , Necrose , Peróxidos/uso terapêutico , Triglicerídeos
7.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 36(9): 1144-1149, 2022 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-36111478

RESUMO

Objective: To explore the value and limitation of transverse cervical artery flap in laryngeal function preservation surgery of hypopharyngeal carcinoma. Methods: Between January 2013 and December 2019, 18 male patients with hypopharyngeal carcinoma were admitted. The patients' age ranged from 48 to 77 years, with a median age of 65 years. The disease duration ranged from 3 to 8 months (mean, 5 months). All patients were diagnosed as squamous cell carcinoma by biopsy before operation. According to the American Joint Committee on Cancer (AJCC) guidelines (2017, 8th ed), TNM staging was T2N0M0 in 9 cases, T2N1M0 in 2 cases, and T3N0M0 in 7 cases, and cTNM staging was stage Ⅱ in 9 cases and stage Ⅲ in 9 cases. The lesions of 15 cases were located in the piriform fossa of hypopharynx on one side, among which the esophageal entrance was involved in 4 cases. The lesions of 3 cases were located in the posterior wall of the hypopharynx with esophageal entrance involvement. After partial pharyngo- laryngectomy and bilateral neck lymph node dissection, the hypopharyngeal and laryngeal defects were repaired with transverse cervical artery flaps, the size of the flap ranged from 4 cm×3 cm to 6 cm×4 cm. The accompanying vein of transverse cervical artery (7 cases), external jugular vein (6 cases), and combination of both (5 cases) served as venous reflux. Retrograde external jugular venous reflux exercise was performed in 2 flaps with venous reflux obstruction during operation. The incisions at donor sites were directly sutured or via relaxed incision sutured. Radiotherapy and chemotherapy were supplemented within 3 months after operation. Tracheal cannula with air bag was used to prevent patients from aspiration in the early postoperative stage. Results: The operation time was 4-6 hours, with an average of 4.5 hours. All patients were followed up 1-5 years (mean, 2 years and 6 months). Postoperative pathological examination showed that 7 cases had cervical lymph node metastases on the affected side, and there was no lymph node metastasis in cervical region Ⅴ; the remaining 11 cases had no lymph node metastasis. After operation, 16 flaps survived successfully, and 2 flaps with external jugular vein reflux were covered with white pseudomembrane, no flap necrosis was found after the pseudomembrane fell off. Four cases had no obvious accidental aspiration after operation; 14 cases had obvious accidental aspiration, of which 13 cases were significantly reduced at 3 months after operation, and 1 case still had obvious accidental aspiration at 6 months after operation, and the accidental aspiration decreased significantly after pulling out the gastric tube. All patients had no aspiration pneumonia. One case developed upper mediastinal lymph node metastasis at 1 year and 2 months after operation, and died of recurrence and pulmonary infection at 1 year and 3 months after operation. No recurrence or metastasis was found in the remaining 17 cases during follow-up. Tracheal cannula was successfully removed in 7 cases at 2-5 months after operation. Different degrees of accidental aspiration in 11 patients were confirmed by esophagography, so the tracheal cannula was retained. All patients had pronunciation function after operation. All incisions at the donor sites healed by first intention, and the shoulder joint function was normal. Conclusion: Using transverse cervical artery flap to repair the hypopharyngeal and laryngeal defects during hypopharyngeal carcinoma surgery in patients without lymph node metastasis in cervical region Ⅴ, can achieve good results of laryngeal function preservation. In cases with suspected lymph node metastasis in cervical region Ⅴ or venous dysplasia of accompanying vein of transverse cervical artery, there is a risk of tumor recurrence or flap necrosis, and the repair method needs to be cautiously employed.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Hipofaríngeas , Idoso , Artérias , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Humanos , Neoplasias Hipofaríngeas/patologia , Neoplasias Hipofaríngeas/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Pescoço , Necrose , Complicações Pós-Operatórias
8.
J Exp Med ; 219(11)2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36069923

RESUMO

Cellular necrosis during Mycobacterium tuberculosis (Mtb) infection promotes both immunopathology and bacterial dissemination. Glutathione peroxidase-4 (Gpx4) is an enzyme that plays a critical role in preventing iron-dependent lipid peroxidation-mediated cell death (ferroptosis), a process previously implicated in the necrotic pathology seen in Mtb-infected mice. Here, we document altered GPX4 expression, glutathione levels, and lipid peroxidation in patients with active tuberculosis and assess the role of this pathway in mice genetically deficient in or overexpressing Gpx4. We found that Gpx4-deficient mice infected with Mtb display substantially increased lung necrosis and bacterial burdens, while transgenic mice overexpressing the enzyme show decreased bacterial loads and necrosis. Moreover, Gpx4-deficient macrophages exhibited enhanced necrosis upon Mtb infection in vitro, an outcome suppressed by the lipid peroxidation inhibitor, ferrostatin-1. These findings provide support for the role of ferroptosis in Mtb-induced necrosis and implicate the Gpx4/GSH axis as a target for host-directed therapy of tuberculosis.


Assuntos
Ferroptose , Glutationa Peroxidase/metabolismo , Tuberculose , Animais , Glutationa/metabolismo , Peroxidação de Lipídeos , Camundongos , Camundongos Transgênicos , Necrose , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Tuberculose/imunologia , Tuberculose/metabolismo
9.
Front Immunol ; 13: 886374, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110858

RESUMO

Fibrosis is defined as the abnormal and excessive deposition of extracellular matrix (ECM) components, which leads to tissue or organ dysfunction and failure. However, the pathological mechanisms underlying fibrosis remain unclear. The inflammatory response induced by tissue injury is closely associated with tissue fibrosis. Recently, an increasing number of studies have linked necroptosis to inflammation and fibrosis. Necroptosis is a type of preprogrammed death caused by death receptors, interferons, Toll-like receptors, intracellular RNA and DNA sensors, and other mediators. These activate receptor-interacting protein kinase (RIPK) 1, which recruits and phosphorylates RIPK3. RIPK3 then phosphorylates a mixed lineage kinase domain-like protein and causes its oligomerization, leading to rapid plasma membrane permeabilization, the release of cellular contents, and exposure of damage-associated molecular patterns (DAMPs). DAMPs, as inflammatory mediators, are involved in the loss of balance between extensive inflammation and tissue regeneration, leading to remodeling, the hallmark of fibrosis. In this review, we discuss the role of necroptotic DAMPs in tissue fibrosis and highlight the inflammatory responses induced by DAMPs in tissue ECM remodeling. By summarizing the existing literature on this topic, we underscore the gaps in the current research, providing a framework for future investigations into the relationship among necroptosis, DAMPs, and fibrosis, as well as a reference for later transformation into clinical treatment.


Assuntos
Alarminas , Apoptose , Alarminas/metabolismo , Apoptose/fisiologia , DNA , Fibrose , Humanos , Inflamação/patologia , Interferons , Necrose/patologia , RNA , Receptores de Morte Celular
11.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 34(4): 361-369, 2022 Aug 18.
Artigo em Chinês | MEDLINE | ID: mdl-36116925

RESUMO

OBJECTIVE: To investigate the effect of Toxoplasma gondii Chinese 1 genotype infections on host brain iron metabolism and brain damages. METHODS: Twenty C57BL/6 mice, each weighing 15 to 17 g, were randomly divided into the control and infection groups, of 10 mice in each group. Each mouse in the infection group was injected intraperitoneally with 4 000 tachyzoites of the TgCtwh3 isolate with Chinese 1 genotype, while each mouse in the control group was injected with an equal amount of sterile phosphate-buffered saline (PBS). All mice were sacrificed 6 day post-infection and brain tissues were sampled. The iron levels were measured in mouse brain specimens using inductively coupled plasma mass spectrometry (ICP-MS). The differentially expressed genes were determined between the experimental and control groups using RNA chips and Gene Ontology (GO) term enrichment analysis of differentially expressed genes was performed. The mRNA expression of Toxoplasma gondii surface antigen 1 (TgSAG1) gene and some Zrt- and Irt-like protein (ZIP) family member coding genes was detected by quantitative real-time PCR (qPCR) assay. The ultrastructure of the hippocampus dentate gyrus in mouse brain specimens was observed using optical and electronic microscopy. The glutathione peroxidase 4 (GPx4) expression was determined using Western blotting, and malondialdehyde (MDA) level was measured using thiobarbituric acid (TBA) test. In addition, the optical density (OD) of vascular endothelial growth factor (VEGF) protein was measured using immunohistochemistry. RESULTS: Optical microscopy showed cell necrosis in the hippocampus dentate gyrus of mouse brain specimens in the infection group, and electronic microscopy cytoplasmic vacuolization, nuclear atrophy and necrosis, disruption of cristae mitochondriales and increased autophagosome levels in the mouse brain hippocampus specimens in the infection group. The iron level was significantly greater in mouse brain specimens in the infection group than in the control group [(32.92 ± 0.90) µg/g vs. (37.72 ± 1.10) µg/g; t = 3.397, P < 0.01]. RNA chips revealed 721 up-regulated genes and 276 down-regulated genes in mouse brain specimens between the infection and control groups, and the differentially expressed genes were significantly enriched in metal ion binding ability (molecular function). Elevated expression of metal element transporter ZIP2 mRNA (t = 8.659, P < 0.05), reduced GPx4 expression [(1.046 ± 0.025) vs. (0.720 ± 0.101); t = 3.129, P < 0.01], increased MDA level [(4.37 ± 0.33) nmol/mgprot vs. (5.93 ± 0.54) nmol/mgprot; t = 2.451, P < 0.05], and up-regulated mean OD of VEGF protein [(0.348 3 ± 0.017 8) vs. (0.490 6 ± 0.010 5); t = 6.641, P < 0.01] were found in mouse brain specimens in the infection group than in the control group. CONCLUSIONS: Chinese 1 genotype T. gondii infection results in iron accumulation in brain tissues, reduced antioxidant ability and elevated levels of oxidative stress in mice, suggesting that T. gondii infection may cause brain damages through affecting iron metabolism in host brain tissues.


Assuntos
Toxoplasma , Toxoplasmose Animal , Animais , Antígenos de Superfície/metabolismo , Antioxidantes/metabolismo , Encéfalo , China , Genótipo , Ferro/metabolismo , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Necrose/metabolismo , Fosfatos/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , RNA , RNA Mensageiro/metabolismo , Toxoplasma/genética , Toxoplasma/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
12.
Adv Surg ; 56(1): 13-35, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36096565

RESUMO

Necrotizing pancreatitis affects 10% to 15% of all patients with acute pancreatitis. Despite improved understanding of this complex disease, it is still attended by up to 15% mortality. Necrotizing pancreatitis provides the clinical challenges of working in a multi-disciplinary group, determining proper timing for intervention, and identifying appropriate intervention approaches. The step-up approach consists of supportive care initially. When there is documented infected necrosis, treatment begins with antibiotics, progressing to minimally invasive mechanical necrosis intervention, and reserving surgery as the final treatment modality. However, treatment must be tailored to the individual patient. This article provides an overview of necrotizing pancreatitis.


Assuntos
Pancreatite Necrosante Aguda , Doença Aguda , Drenagem , Humanos , Necrose , Pancreatite Necrosante Aguda/diagnóstico , Pancreatite Necrosante Aguda/cirurgia
13.
Zhonghua Xin Xue Guan Bing Za Zhi ; 50(9): 907-912, 2022 Sep 24.
Artigo em Chinês | MEDLINE | ID: mdl-36096709

RESUMO

Objective: To explore the safety and feasibility of stereotactic radiation therapy (SBRT) strategy for irradiating porcine ventricular septum, see if can provide a preliminary experimental evidence for clinical SBRT in patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods: Five male pigs (39-49 kg, 6 months old) were used in this study. Pigs were irradiated at doses of 25 Gy (n=2) or 40 Gy (n=3). Delineation of the target volume was achieved under the guidance of 3-dimensional CT image reconstruction, and SBRT was then performed on defined target volume of porcine ventricular septum. Blood biomarkers, electrocardiogram and echocardiography parameters were monitored before and after SBRT. Pathological examination (HE staining, Masson staining) was performed on the target and non-target myocardium at 6 months post SBRT. Results: SBRT was successful and all animals survived to the designed study endpoint (6 months) after SBRT. Serum cardiac troponin T (cTnT) level was significantly higher than the baseline level at 1 day post SBRT, and reduced at 1 week after SBRT, but was still higher than the baseline level(P<0.05). Serum N-terminal pro-B type natriuretic peptide (NT-proBNP) was also significantly increased at 1 day post SBRT (P<0.05) and returned to baseline level at 1 week post SBRT. The serum NT-proBNP level was (249±78), (594±37) and (234±46) pg/ml, respectively, and the cTnT was (14±7), (240±40) and (46±34) pg/ml, respectively at baseline, 1 day and 1 week after SBRT in the 40 Gy dose group. The serum NT-proBNP level was (184±20), (451±49) and (209±36) pg/ml, respectively, the cTnT values ​​were (9±1), (176±29) and (89±27) pg/ml, respectively at baseline, 1 day and 1 week after SBRT in the 25 Gy dose group. Both NT-proBNP and cTnT values tended to be higher post SBRT in the 40 Gy dose group as compared with the 25 Gy dose group, but the difference was not statistically significant (P>0.05). The left ventricular ejection fraction and the left ventricular end-diastolic diameter remained unchanged before and after SBRT (P>0.05). The interventricular septum thickness showed a decreasing trend at 6 months after SBRT, but the difference was not statistically significant ((9.54±0.24) mm vs. (9.82±8.00) mm, P>0.05). The flow velocity of the left ventricular outflow tract, and the valve function and morphology were not affected by SBRT. At 6 months after SBRT, HE staining revealed necrosis in the irradiated target area of ​​the myocardium in the 40 Gy dose group and the 25 Gy dose group, and the degree of necrosis in the irradiated interventricular septum was more obvious in the 40 Gy dose group as compared with the 25 Gy group. The combined histological analysis of the two groups showed that the necrotic area of ​​the irradiated target area accounted for (26±9)% of the entire interventricular septum area, which was higher than that of the non-irradiated area (0) (P<0.05). There was no damage or necrosis of myocardial tissue outside the target irradiation area in both groups. The results of Masson staining showed that the percentage area of myocardial fibrosis was significantly higher in the irradiated target area than non-irradiated area ((12.6±5.3)% vs. (2.5±0.8)%, P<0.05). Conclusion: SBRT is safe and feasible for irradiating porcine ventricular septum.


Assuntos
Radiocirurgia , Septo Interventricular , Animais , Estudos de Viabilidade , Masculino , Necrose , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Volume Sistólico , Suínos , Função Ventricular Esquerda
14.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 47(8): 1129-1135, 2022 Aug 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-36097781

RESUMO

OBJECTIVES: Placenta accreta spectrum disorders (PAS) refers to a group of abnormalities in placental adhesion and invasion, which may lead to serious complications such as intractable postpartum hemorrhage. The use of low-level extra-abdominal aortic temporary block during cesarean section may reduce intraoperative bleeding in patients with PAS, but it may also cause ischemia-reperfusion injury. In this study, we intend to investigate the efficacy of low extra-abdominal aortic block in cesarean section for placental implantation disease and its effect on malondialdehyde (MDA) level and superoxide dismutase (SOD) activity, and analyze the severity of ischemia-reperfusion injury caused by them. METHODS: Pregnant women with invasive placenta accreta spectrum disorders who delivered in the Department of Obstetrics and Gynecology of the Third Xiangya Hospital of Central South University from July 2017 to July 2021, were selected, and they were divided into 2 groups. Group A consisted of those who underwent low extra-abdominal aortic block during cesarean section (n=15) and group B consisted of those who did not undergo extra-abdominal aortic block (n=15). The intraoperative bleeding, blood transfusion, hysterectomy and complication rate, postoperative hospital stay and hospitalization expenses were compared between the 2 groups to analyze the efficacy of abdominal aortic block. The biochemical indexes related to ischemia-reperfusion, MDA content and total superoxide dismutase (T-SOD) activity, were measured at the corresponding time points in both groups. The time points of each test were: in group A, before the block of the low extra-abdominal aorta after delivery (A0), 0 h (A1, when the myometrium was started to be sutured), 0.5 h (A2), 2 h (A3), and 4 h (A4) after the open block; in group B, after delivery of the fetus (B0), 0 h (B1), 0.5 h (B2), 2 h (B3), and 4 h (B4) after the myometrium was started to be sutured. Total duration of abdominal aortic block in group A was also recorded. Both groups were observed for sings of edema, ischemia, necrosis and infection in the limbs after surgery. The severity of ischemia-reperfusion injury caused by abdominal aortic block were determined by detecting the relevant biochemical indexes at different moments of reperfusion. RESULTS: The intraoperative bleeding and blood transfusion in group A were less than those in group B, and the difference was statistically significant (P<0.05). There was no significant difference in postoperative hospital stay and hospitalization expenses between the 2 groups (P>0.05). Surgical complications: in group A, the uterus was preserved in all cases, there was 1 bladder injury and 2 pelvic infections; while in group B, there was 1 hysterectomy, 3 bladder injuries, and 3 pelvic infections. Changes in T-SOD and MDA values: compared with A0 before block, the MDA level was significantly elevated in blood at time points A1, A2, and A3, while SOD activity was significantly decreased (P<0.05), and the 2 observed indexes basically returned to A1 level (ischemic period) at 4 h after open block (A4). There was no significant difference in the changes of T-SOD and MDA in group B (P>0.05). Comparison of T-SOD and MDA levels between group A and B: the difference of the 2 indexes was not statistically significant between A0 and B0 (P>0.05), MDA level was not statistically significant between A1 and B1, T-SOD activity at A1 was lower than B1, the difference was statistically significant, at the rest of the same time point, MDA level in group A were higher than that in group B, T-SOD activity in group A were lower than that in group B, the difference was statistically significant (P<0.05). No postoperative limb edema, ischemia, necrosis, or infection occurred in both groups. CONCLUSIONS: Low-level extra-abdominal aortic block effectively reduces bleeding and transfusion during cesarean section for placenta accreta spectrum disorders, resulting in a transient MDA elevation and a decrease of SOD activity, which means causing transient ischemia-reperfusion injury without complications such as limb edema, ischemia, necrosis, and infection.


Assuntos
Infecção Pélvica , Placenta Acreta , Traumatismo por Reperfusão , Aorta Abdominal/metabolismo , Aorta Abdominal/cirurgia , Cesárea , Feminino , Humanos , Isquemia , Necrose , Placenta/metabolismo , Placenta Acreta/cirurgia , Gravidez , Superóxido Dismutase/metabolismo
15.
Pak J Biol Sci ; 25(9): 835-842, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36098086

RESUMO

<b>Background and Objective:</b> Hepatitis is a liver illness caused by a viral infection, autoimmune conditions or the use of certain medicines. In molecular hepatitis treatment, cytochrome c can be used as a potential predictor of the severity of liver impairment. In Asia, particularly in Indonesia, antioxidant-rich plants include <i>Ficus</i> <i>carica</i> and <i>Olea europaea.</i> This study aimed to see what impact cytochrome c in hepatitis after these two botanicals were administered. <b>Materials and Methods:</b> Rats were grouped as follows: Normal rats with no additions or herbs (G<sub>0</sub>), the physiological solution group (G<sub>1</sub>), the intravenous administration of the quercetin-copper (II) (G<sub>2</sub>), Olive leaf extract or OLE (300 mg kg<sup></sup><sup>1</sup> b.wt.) (G<sub>3</sub>) and Tin leaf extract or TLE (100 mg kg<sup></sup><sup>1</sup> b.wt.) (G<sub>4</sub>). For an animal model of hepatitis, the rats were given thioacetamide 280 mg kg<sup></sup><sup>1</sup> b.wt., 8 days later. The rats were dissected and blood and liver samples were collected for enzyme and immunohistochemistry examination. <b>Results:</b> Malondialdehyde (MDA), superoxide dismutase (SOD) and cytochrome c expression levels differed significantly (p<0.05) across treatment groups in rat's models of hepatitis. Hepatocytes first displayed symptoms of lipid degradation, inflammatory and necrosis cells. When administered quercetin and the two herbs, necrosis and inflammatory cells were reduced, demonstrating that OLE and TLE can enhance liver histology and lower cytochrome c expression in a mouse model of hepatitis. <b>Conclusion:</b> Administration of Olive leaf extract (OLE) and Tin leaf extract (TLE) can improve liver histology in hepatitis model rats while decreasing cytochrome c expression, which is a mechanism for hepatocyte cell death.


Assuntos
Hepatite , Olea , Animais , Citocromos c , Etanol , Camundongos , Necrose , Olea/química , Estresse Oxidativo , Extratos Vegetais/farmacologia , Quercetina , Ratos , Estanho
16.
Front Immunol ; 13: 982040, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059539

RESUMO

Cell death is generally classified into two categories: regulated cell death (RCD) and accidental cell death (ACD). In particular, RCD is a kind of genetically controlled process, including programmed apoptotic death and programmed necrotic death. Pyroptosis, an inflammatory form of programmed necrotic death, causes inflammation in cells. The influence of pyroptosis on tumor is complicated. On the one hand, pyroptosis triggers antitumor response. On the other hand, pyroptosis may induce carcinogenesis. Pyroptosis is initiated by various factors, especially non-coding RNAs. In this review, we discuss the effects of ncRNAs on pyroptosis and the mechanisms by which ncRNAs initiate pyroptosis. Moreover, we introduce the influence of ncRNA on tumor resistance via pyroptosis. Additionally, we summarize how ncRNA-associated pyroptosis modulates the tumor microenvironment (TME) and thereafter triggers antitumor immune response. Finally, pyroptosis-related ncRNAs are promising diagnostic and immunotherapeutic biomarkers and therapeutic targets.


Assuntos
Neoplasias , Piroptose , Apoptose , Humanos , Necrose , Neoplasias/genética , RNA não Traduzido/genética , Microambiente Tumoral
17.
J Cell Sci ; 135(17)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36098620

RESUMO

Necroptosis, or programmed necrosis, is an inflammatory form of cell death with important functions in host defense against pathogens and tissue homeostasis. The four cytosolic receptor-interacting protein kinase homotypic interaction motif (RHIM)-containing adaptor proteins RIPK1, RIPK3, TRIF (also known as TICAM1) and ZBP1 mediate necroptosis induction in response to infection and cytokine or innate immune receptor activation. Activation of the RHIM adaptors leads to phosphorylation, oligomerization and membrane targeting of the necroptosis effector protein mixed lineage kinase domain-like (MLKL). Active MLKL induces lesions on the plasma membrane, leading to the release of pro-inflammatory damage-associated molecular patterns (DAMPs). Thus, activities of the RHIM adaptors and MLKL are tightly regulated by posttranslational modifications to prevent inadvertent release of immunogenic contents. In this Cell Science at a Glance article and the accompanying poster, we provide an overview of the regulatory mechanisms of necroptosis and its biological functions in tissue homeostasis, pathogen infection and other inflammatory diseases.


Assuntos
Apoptose , Necroptose , Morte Celular , Humanos , Necroptose/genética , Necrose , Fosforilação
18.
In Vivo ; 36(5): 2052-2060, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36099118

RESUMO

BACKGROUND/AIM: BAT-90 is an innovative active implantable device designed for the irradiation of unresectable tumors (e.g., liver cancer) or surgical tumor beds, based on the combination of Yttrium-90 beta-emitting microspheres and a tissue adhesive hydrogel, currently used in cardio-vascular surgery. The rationale behind BAT-90 is to localize the Yttrium-90 activity on the administration site, while minimizing its body dispersion. MATERIALS AND METHODS: The effective induction of necrosis in the target injection area was tested in a pig liver model, whereas the safety of BAT-90 was assessed and demonstrated in biocompatibility tests for acute systemic toxicity, intracutaneous reactivity, delayed hypersensitivity and subcutaneous implantation. RESULTS: BAT-90 administration induced necrosis into the target site, while the safety experiments in the treated animals highlighted results very similar to the controls. CONCLUSION: BAT-90 could be considered as a safe and innovative treatment option for inoperable solid tumors of the liver.


Assuntos
Neoplasias Hepáticas , Radioisótopos de Ítrio , Animais , Neoplasias Hepáticas/radioterapia , Microesferas , Necrose , Suínos , Radioisótopos de Ítrio/efeitos adversos
19.
Diving Hyperb Med ; 52(3): 164-174, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36100927

RESUMO

INTRODUCTION: Hyperbaric oxygen treatment (HBOT) is sometimes used in the management of open fractures and severe soft tissue crush injury, aiming to reduce complications and improve outcomes. METHODS: Patients with open tibial fractures were randomly assigned within 48 hours of injury to receive standard trauma care or standard care plus 12 sessions of HBOT. The primary outcome was the incidence of necrosis or infection or both occurring within 14 days of injury. RESULTS: One-hundred and twenty patients were enrolled. Intention to treat primary outcome occurred in 25/58 HBOT assigned patients and 34/59 controls (43% vs 58%, odds ratio (OR) 0.55, 95% confidence interval (CI) 0.25 to 1.18, P = 0.12). Tissue necrosis occurred in 29% of HBOT patients and 53% of controls (OR 0.35, 95% CI 0.16 to 0.78, P = 0.01). There were fewer late complications in patients receiving HBOT (6/53 vs 18/52, OR 0.22, 95% CI 0.08 to 0.64, P = 0.007) including delayed fracture union (5/53 vs 13/52, OR 0.31, 95% CI 0.10 to 0.95, P = 0.04). Quality of life measures at one and two years were superior in HBOT patients. The mean score difference in short form 36 was 2.90, 95% CI 1.03 to 4.77, P = 0.002, in the short musculoskeletal function assessment (SMFA) was 2.54, 95% CI 0.62 to 4.46, P = 0.01; and in SMFA daily activities was 19.51, 95% CI 0.06 to 21.08, P = 0.05. CONCLUSIONS: In severe lower limb trauma, early HBOT reduces tissue necrosis and the likelihood of long-term complications, and improves functional outcomes. Future research should focus on optimal dosage and whether HBOT has benefits for other injury types.


Assuntos
Fraturas Expostas , Oxigenoterapia Hiperbárica , Fraturas Expostas/terapia , Humanos , Extremidade Inferior , Necrose , Qualidade de Vida
20.
BMC Gastroenterol ; 22(1): 405, 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36057565

RESUMO

BACKGROUND: In acute pancreatitis, secondary infection of pancreatic necrosis is a complication that mostly necessitates interventional therapy. A reliable prediction of infected necrotizing pancreatitis would enable an early identification of patients at risk, which however, is not possible yet. METHODS: This study aims to identify parameters that are useful for the prediction of infected necrosis and to develop a prediction model for early detection. We conducted a retrospective analysis from the hospital information and reimbursement data system and screened 705 patients hospitalized with diagnosis of acute pancreatitis who underwent contrast-enhanced computed tomography and additional diagnostic puncture or drainage of necrotic collections. Both clinical and laboratory parameters were analyzed for an association with a microbiologically confirmed infected pancreatic necrosis. A prediction model was developed using a logistic regression analysis with stepwise inclusion of significant variables. The model quality was tested by receiver operating characteristics analysis and compared to single parameters and APACHE II score. RESULTS: We identified a total of 89 patients with necrotizing pancreatitis, diagnosed by computed tomography, who additionally received biopsy or drainage. Out of these, 59 individuals had an infected necrosis. Eleven parameters showed a significant association with an infection including C-reactive protein, albumin, creatinine, and alcoholic etiology, which were independent variables in a predictive model. This model showed an area under the curve of 0.819, a sensitivity of 0.692 (95%-CI [0.547-0.809]), and a specificity of 0.840 (95%-CI [0.631-0.947]), outperforming single laboratory markers and APACHE II score. Even in cases of missing values predictability was reliable. CONCLUSION: A model consisting of a few single blood parameters and etiology of pancreatitis might help for differentiation between infected and non-infected pancreatic necrosis and assist medical therapy in acute necrotizing pancreatitis.


Assuntos
Pancreatite Necrosante Aguda , Doença Aguda , Humanos , Necrose , Pancreatite Necrosante Aguda/complicações , Pancreatite Necrosante Aguda/diagnóstico , Pancreatite Necrosante Aguda/patologia , Estudos Retrospectivos
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