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1.
BMC Plant Biol ; 24(1): 114, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365570

RESUMO

BACKGROUND: The small YABBY plant-specific transcription factor has a prominent role in regulating plant growth progress and responding to abiotic stress. RESULTS: Here, a total of 16 PvYABBYs from switchgrass (Panicum virgatum L.) were identified and classified into four distinct subgroups. Proteins within the same subgroup exhibited similar conserved motifs and gene structures. Synteny analyses indicated that segmental duplication contributed to the expansion of the YABBY gene family in switchgrass and that complex duplication events occurred in rice, maize, soybean, and sorghum. Promoter regions of PvYABBY genes contained numerous cis-elements related to stress responsiveness and plant hormones. Expression profile analysis indicated higher expression levels of many PvYABBY genes during inflorescence development and seed maturation, with lower expression levels during root growth. Real-time quantitative PCR analysis demonstrated the sensitivity of multiple YABBY genes to PEG, NaCl, ABA, and GA treatments. The overexpression of PvYABBY14 in Arabidopsis resulted in increased root length after treatment with GA and ABA compared to wild-type plants. CONCLUSIONS: Taken together, our study provides the first genome-wide overview of the YABBY transcription factor family, laying the groundwork for understanding the molecular basis and regulatory mechanisms of PvYABBY14 in response to ABA and GA responses in switchgrass.


Assuntos
Arabidopsis , Panicum , Panicum/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Reguladores de Crescimento de Plantas , Genes de Plantas , Estresse Fisiológico/genética , Fatores de Transcrição/genética , Regulação da Expressão Gênica de Plantas , Filogenia , Proteínas de Plantas/metabolismo
2.
Appl Environ Microbiol ; : e0114624, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39287399

RESUMO

In the actual industrial production process, the efficient biosynthesis and secretion of Monascus pigments (MPs) tend to take place under abiotic stresses, which often result in an imbalance of cell homeostasis. The present study aimed to thoroughly describe the changes in lipid profiles in Monascus purpureus by absolute quantitative lipidomics and tandem mass tag-based quantitative proteomics. The results showed that ammonium chloride stress (15 g/L) increased MP production while inhibiting ergosterol biosynthesis, leading to an imbalance in membrane lipid homeostasis in Monascus. In response to the imbalance of lipid homeostasis, the regulation mechanism of phospholipids in Monascus was implemented, including the inhibition of lysophospholipids production, maintenance of the ratio of PC/PE, and improvement of the biosynthesis of phosphatidylglycerol, phosphatidylserine, and cardiolipin with high saturated and long carbon chain fatty acids through the CDP-DG pathway rather than the Kennedy pathway. The inhibition of lysophospholipid biosynthesis was attributed to the upregulated expression of protein and its gene related to lysophospholipase NTE1, while maintenance of the PC/PE ratio was achieved by the upregulated expression of protein and its gene related to CTP: phosphoethanolamine cytidylyltransferase and phosphatidylethanolamine N-methyltransferase in the Kennedy pathway. These findings provide insights into the regulation mechanism of MP biosynthesis from new perspectives.IMPORTANCEMonascus is important in food microbiology as it produces natural colorants known as Monascus pigments (MPs). The industrial production of MPs has been achieved by liquid fermentation, in which the nitrogen source (especially ammonium chloride) is a key nutritional parameter. Previous studies have investigated the regulatory mechanisms of substance and energy metabolism, as well as the cross-protective mechanisms in Monascus in response to ammonium chloride stress. Our research in this work demonstrated that ammonium chloride stress also caused an imbalance of membrane lipid homeostasis in Monascus due to the inhibition of ergosterol biosynthesis. We found that the regulation mechanism of phospholipids in Monascus was implemented, including inhibition of lysophospholipids production, maintenance of the ratio of PC/PE, and improvement of biosynthesis of phosphatidylglycerol, phosphatidylserine, and cardiolipin with high saturated and long carbon chain fatty acids through the CDP-DG pathway. These findings further refine the regulatory mechanisms of MP production and secretion.

3.
Surg Endosc ; 38(1): 240-252, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37978082

RESUMO

BACKGROUND: Few cases describing patients with a right aortic arch (RAA) or double aortic arch (DAA) and esophageal cancer (EC) have been reported. METHODS: We analyzed RAA and DAA cases treated with esophagectomy in our center's database and reported in English-language studies until April 1, 2023. Our study assessed the malformation characteristics and surgical details of EC patients with RAA and DAA. RESULTS: We extracted data of 24 EC patients with RAAs and 10 EC patients with DAAs. In both groups, the patients were more likely to be Japanese and male, to have squamous cell carcinoma and to have tumors located in the upper thoracic esophagus or middle thoracic esophagus. Left thoracotomy was commonly applied for RAA patients. For DAA patients, the proportions of left-sided and right-sided approaches were similar. Esophagectomy under video-assisted thoracoscopic surgery (VATS) in RAA or DAA patients had been performed on a routine basis in recent years. There were two anastomotic leakages in each group. Specifically, Kommerell diverticulum rupture occurred in 1 RAA patient; gastric tube dilation occurred in 1 DAA patient; and recurrent laryngeal nerve (RLN) injury occurred in 2 RAA patients. The postoperative course was uneventful for most patients in both cohorts. CONCLUSIONS: Esophageal carcinoma is rarely seen in patients with an RAA or DAA. To adequately dissect superior mediastinal LNs, an auxiliary incision (such as sternotomy), the left door open method or a preceding cervical procedure should be used appropriately. Esophagectomy, whether via thoracotomy or thoracoscopic surgery, can be performed safely for both RAA and DAA.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Anel Vascular , Humanos , Masculino , Anel Vascular/complicações , Anel Vascular/cirurgia , Anel Vascular/patologia , Aorta Torácica/cirurgia , Aorta Torácica/anormalidades , Aorta Torácica/patologia , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Cirurgia Torácica Vídeoassistida , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Estudos Retrospectivos
4.
Mol Breed ; 43(5): 35, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37312751

RESUMO

The plant height and leaf color are important traits in crops since they contribute to the production of grains and biomass. Progress has been made in mapping the genes that regulate plant height and leaf color in wheat (Triticum aestivum L.) and other crops. Wheat line DW-B (dwarfing, white leaves, and blue grains) with semi-dwarfing and albinism at the tillering stage and re-greening at the jointing stage was created using Lango and Indian Blue Grain. Transcriptomic analyses of the three wheat lines at the early jointing stages indicated that the genes of gibberellin (GA) signaling pathway and chlorophyll (Chl) biosynthesis were expressed differently in DW-B and its parents. Furthermore, the response to GA and Chl contents differed between DW-B and its parents. The dwarfing and albinism in DW-B were owing to defects in the GA signaling pathway and abnormal chloroplast development. This study can improve understanding of the regulation of plant height and leaf color. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01379-z.

5.
World J Surg Oncol ; 21(1): 41, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36765428

RESUMO

BACKGROUND: As the preoperative examination of esophageal cancer has improved, the likelihood of finding diseases in other organs that require surgical treatment has also increased. The purpose of this study was to explore the feasibility of combined surgery for esophageal cancer by analyzing the occurrence of postoperative complications in patients with esophageal cancer. METHODS: The clinical characteristics of 1566 patients with esophageal cancer who underwent thoracic surgery in our hospital between January 2017 and September 2022 were analyzed retrospectively. The feasibility of combined surgery for esophageal cancer was analyzed by comparing postoperative complications in patients who underwent simple esophageal cancer surgery (SEC) with those in patients who underwent combined surgery for esophageal cancer (COEC). The tendency scores of patients in the COEC and SEC groups (1:2) were matched to balance the confounding clinical factors, and the difference in postoperative complications was further analyzed. Moreover, we performed a subgroup analysis of esophagectomy combined with lung resection (ECL). In addition, the independent risk factors for postoperative Clavien-Dindo ≥ grade III complications of esophageal cancer were analyzed by multivariate logistic regression. RESULTS: A total of 1566 patients (1147 (73.2%) males and 419 (26.8%) females), with an average age of 64.2 years, were analyzed. There was no significant difference in postoperative complications between the SEC and COEC groups according to the Clavien-Dindo classification (P=0.713). An analysis of the complications revealed that those in the COEC group had a higher incidence of lung consolidation than those in the SEC group (P=0.007). However, when we performed propensity score matching (PSM) on the SEC and COEC groups, there was still no significant difference in complications according to the Clavien-Dindo classification (P=0.346); furthermore, when a detailed analysis of complications was performed, there was no significant difference between the two. In subgroup analysis, after we performed PSM in ECL patients and SEC patients, we also found no significant difference in postoperative complications between patients with ECL and patients with SEC. In addition, we found that a history of diabetes (OR=1.604, P=0.029, 95% CI=1.049-2.454), a history of coronary heart disease (OR=1.592, P=0.046, 95% CI=1.008-2.515), diffusing capacity of the lungs for carbon monoxide (DLCO) (OR=0.916, P=0.024, 95% CI=0.849-0.988), and ALB level (OR=0.955, P=0.007, 95% CI=0.924-0.987) were independent factors that influenced postoperative complications in esophageal cancer patients with grade III or higher complications. CONCLUSION: Combined surgery for esophageal cancer does not increase the incidence of postoperative complications. In addition, a history of diabetes mellitus or coronary heart disease, carbon monoxide dispersion, and preoperative ALB level are independent risk factors for grade III or higher postoperative complications of esophageal cancer.


Assuntos
Monóxido de Carbono , Neoplasias Esofágicas , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Estudos de Viabilidade , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Esofagectomia/efeitos adversos
6.
Bioprocess Biosyst Eng ; 46(10): 1399-1410, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37486422

RESUMO

Most cold-adapted enzymes display high catalytic activity at low temperatures (20-25 °C) and can still maintain more than 40-50% of their maximum activity at lower temperatures (0-10 °C) but are inactivated after a moderate increase in temperature. The activity of some cold-adapted enzymes increases significantly in the presence of high salt concentrations and metal ions. Interestingly, we also observed that some cold-adapted enzymes have a wide range of optimum temperatures, exhibiting not only maximum activity under low-temperature conditions but also the ability to maintain high enzyme activity under high-temperature conditions, which is a novel feature of cold-adapted enzymes. This unique property of cold-adapted enzymes is generally attractive for biotechnological and industrial applications because these enzymes can reduce energy consumption and the chance of microbial contamination, thereby lowering the production costs and maintaining the flavor, taste and quality of foods. How high catalytic activity is maintained at low temperatures remains unknown. The relationship between the structure of cold-adapted enzymes and their activity, flexibility and stability is complex, and thus far, a unified explanation has not been provided. Herein, we systematically review the sources, catalytic characteristics and cold adaptation of enzymes from four enzymes categories systematically and discuss how these properties may be exploited in biotechnology. A thorough understanding of the properties, catalytic mechanisms, and engineering of cold-adapted enzymes is critical for future biotechnological applications in the detergent industry and food and beverage industries.


Assuntos
Biotecnologia , Temperatura Baixa , Catálise , Adaptação Fisiológica , Enzimas/química
7.
Int J Mol Sci ; 24(9)2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37176157

RESUMO

The transformation efficiency (TE) was improved by a series of special chemical and physical methods using immature embryos from the cultivar Fielder, with the PureWheat technique. To analyze the reaction of immature embryos infected, which seemed to provide the necessary by Agrobacterium tumefaciens in PureWheat, a combination of scanning electron microscopy (SEM), complete transcriptome analysis, and metabolome analysis was conducted to understand the progress. The results of the SEM analysis revealed that Agrobacterium tumefaciens were deposited under the damaged cortex of immature embryos as a result of pretreatment and contacted the receptor cells to improve the TE. Transcriptome analysis indicated that the differentially expressed genes were mainly enriched in phenylpropanoid biosynthesis, starch and sucrose metabolism, plant-pathogen interaction, plant hormone signal transduction, and the MAPK (Mitogen-activated protein kinase) signaling pathway. By analyzing the correlation between differentially expressed genes and metabolites, the expression of many genes and the accumulation of metabolites were changed in glucose metabolism and the TCA cycle (Citrate cycle), as well as the amino acid metabolism; this suggests that the infection of wheat embryos with Agrobacterium is an energy-demanding process. The shikimate pathway may act as a hub between glucose metabolism and phenylpropanoid metabolism during Agrobacterium infection. The downregulation of the F5H gene and upregulation of the CCR gene led to the accumulation of lignin precursors through phenylpropanoid metabolism. In addition, several metabolic pathways and oxidases were found to be involved in the infection treatment, including melatonin biosynthesis, benzoxazinoid biosynthesis, betaine biosynthesis, superoxide dismutase, and peroxidase, suggesting that wheat embryos may be under the stress of Agrobacterium and, thus, undergo an oxidative stress response. These findings explore the physiological and molecular changes of immature embryos during the co-culture stage of the PureWheat technique and provide insights for Agrobacterium-mediated transgenic wheat experiments.


Assuntos
Agrobacterium tumefaciens , Triticum , Agrobacterium tumefaciens/genética , Triticum/metabolismo , Transcriptoma , Plantas Geneticamente Modificadas/genética , Perfilação da Expressão Gênica , Glucose/metabolismo
8.
Esophagus ; 20(4): 595-604, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37490217

RESUMO

Esophagectomy is currently the mainstay of treatment for resectable esophageal carcinoma. Gastric grafts are the first substitutes in esophageal reconstruction. According to the different tailoring methods applied to the stomach, gastric grafts can be classified as whole stomach, subtotal stomach and gastric tube. Gastric-tube placement has been proven to be the preferred method, with advantages in terms of postoperative complications and long-term survival. In recent years, several novel methods involving special-shaped gastric tubes have been proposed, which have further decreased the incidence of perioperative complications. This article will review the progress and clinical application status of different types of gastric grafts from the perspectives of preparation methods, studies of anatomy and perioperative outcomes, existing problems and future outlook.


Assuntos
Carcinoma , Neoplasias Esofágicas , Humanos , Esofagectomia/efeitos adversos , Estômago/cirurgia , Carcinoma/patologia , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia
9.
Int J Cancer ; 148(2): 437-447, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-32683685

RESUMO

In recent years, inhibitors of the BET bromodomain proteins, such as BRD4 inhibitors, have demonstrated robust antitumor activity. JQ-1, a representative small molecular BRD4 inhibitor, is also effective to block PD-1/PD-L1 signaling by significantly decreasing the PD-L1 expression on tumor cells. However, toxicity of BRD4 inhibitors on lymphoid and hematopoietic tissues limits their clinical usage. In this research, we designed and studied an immunogenic BRD4 inhibitor, SZU-119, by coupling JQ-1 with a TLR7 agonist, SZU-101. In vitro, SZU-119 stimulated the production of cytokines in mouse BMDCs and spleen lymphocytes, and inhibited the expression of PD-L1 in mouse B16 tumor cells. In vivo, SZU-119 suppressed the B16 tumor growth at both injected and uninjected sites, and prolonged the survival time of mice. SZU-119 elevated the number of total CD8+ and IFN-γ+ CD8+ T cells in spleens, with greater CTL cytotoxicity to B16 tumor cells. It was also observed that the infiltration of CD8+ T cells was increased in tumors at both local and distant sites, and the PD-L1 expression was decreased in tumor cells at the primary site. In conclusion, we have demonstrated that SZU-119 activated the innate immune cells, kept efficacy of PD-L1 blockade and abrogated immune toxicity, showing more potent antitumor effects than the simple mixture of SZU-101 and JQ-1 in a mouse melanoma model. Our work provides new insights for the development of anti-melanoma drugs that concurrently target innate and adaptive immunity.


Assuntos
Adenina/análogos & derivados , Azepinas/química , Azepinas/farmacologia , Melanoma Experimental/tratamento farmacológico , Glicoproteínas de Membrana/agonistas , Succinatos/química , Succinatos/farmacologia , Receptor 7 Toll-Like/agonistas , Triazóis/química , Triazóis/farmacologia , Adenina/química , Adenina/farmacologia , Animais , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/biossíntese , Antígeno B7-H1/imunologia , Citocinas/biossíntese , Citocinas/imunologia , Sinergismo Farmacológico , Imunomodulação/efeitos dos fármacos , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia
10.
Zygote ; 29(4): 260-263, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33612133

RESUMO

Intact human sperm DNA is an essential prerequisite for successful fertilization and embryo development. Abnormal sperm DNA fragmentation is a independent factor for male infertility. The objective of this study was to investigate the effects of Peijingsu, a health product, on the DNA integrity of human sperm. Peijingsu was administered for 15 days to 22 patients who had an abnormal sperm DNA fragmentation index (DFI). The DFIs before and after treatment were compared and analyzed using paired t-test. DFIs decreased significantly (P = 0.0008) after treatment, therefore it was concluded that Peijingsu effectively improved sperm DNA integrity in infertile patients who had an abnormal sperm DFI.


Assuntos
Infertilidade Masculina , DNA/genética , Fragmentação do DNA , Fertilização in vitro , Humanos , Infertilidade Masculina/genética , Masculino , Espermatozoides
11.
Molecules ; 26(9)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33946973

RESUMO

The change in phenols, polysaccharides and volatile profiles of noni juice from laboratory- and factory-scale fermentation was analyzed during a 63-day fermentation process. The phenol and polysaccharide contents and aroma characteristics clearly changed according to fermentation scale and time conditions. The flavonoid content in noni juice gradually increased with fermentation. Seventy-three volatile compounds were identified by solid-phase microextraction coupled with gas chromatography-mass spectrometry (SPME-GC-MS). Methyl hexanoate, 3-methyl-3-buten-1-ol, octanoic acid, hexanoic acid and 2-heptanone were found to be the main aroma components of fresh and fermented noni juice. A decrease in octanoic acid and hexanoic acid contents resulted in the less pungent aroma in noni juice from factory-scale fermentation. The results of principal component analysis of the electronic nose suggested that the difference in nitrogen oxide, alkanes, alcohols, and aromatic and sulfur compounds, contributed to the discrimination of noni juice from different fermentation times and scales.


Assuntos
Fermentação , Morinda/química , Fenóis/análise , Polissacarídeos/análise , Compostos Orgânicos Voláteis/análise , Nariz Eletrônico , Cromatografia Gasosa-Espectrometria de Massas , Cinética
12.
J Transl Med ; 18(1): 112, 2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-32131853

RESUMO

BACKGROUND: The global burden of hepatitis B virus (HBV) infection in terms of morbidity and mortality is immense. Novel treatments that can induce a protective immune response are urgently needed to effectively control the HBV epidemic and eventually eradicate chronic HBV infection. METHODS: We designed and evaluated an HBV therapeutic vaccine consisting of a novel Toll-like receptor 7 (TLR7) agonist T7-EA, an Alum adjuvant and a recombinant HBsAg protein. We used RNA-seq, ELISA and hTLR7/8 reporting assays to characterize T7-EA in vitro and real-time PCR to evaluate the tissue-retention characteristics in vivo. To evaluate the adjuvant potential, we administrated T7-EA intraperitoneally in a formulation with an Alum adjuvant and HBsAg in normal and HBV mice, then, we evaluated the HBsAg-specific immune responses by ELISA and Elispot assays. RESULTS: T7-EA acted as an hTLR7-specific agonist and induced a similar gene expression pattern as an unmodified TLR7 ligand when Raw 264.7 cells were exposed to T7-EA; however, T7-EA was more potent than the unmodified TLR7 ligand. In vivo studies showed that T7-EA had tissue-retaining activity with stimulating local cytokine and chemokine expression for up to 7 days. T7-EA could induce Th1-type immune responses, as evidenced by an increased HBsAg-specific IgG2a titer and a T-cell response in normal mice compared to mice received traditional Alum-adjuvant HBV vaccine. Importantly, T7-EA could break immune tolerance and induce persistent HBsAg-specific antibody and T-cell responses in an HBV mouse model. CONCLUSIONS: T7-EA might be a candidate adjuvant in a prophylactic and therapeutic HBV vaccine.


Assuntos
Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Adjuvantes Imunológicos/farmacologia , Animais , Anticorpos Anti-Hepatite B , Vacinas contra Hepatite B , Imunidade , Camundongos , Camundongos Endogâmicos BALB C , Receptor 7 Toll-Like
15.
Mediators Inflamm ; 2019: 9483647, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31011288

RESUMO

CD4+ T-cells play crucial roles in the injured heart. However, the way in which different CD4+ T subtypes function in the myocardial infarction/reperfusion (MI/R) heart is still poorly understood. We aimed to detect the dynamic profile of distinct CD4+ subpopulation-associated cytokines/chemokines by relying on a closed-chest acute murine MI/R model. The protein levels of 26 CD4+ T-cell-associated cytokines/chemokines were detected in the heart tissues and serum of mice at day 7 and day 14 post-MI/R or sham surgery. The mRNA levels of IL-4, IL-6, IL-13, IL-27, MIP-1ß, MCP-3, and GRO-α were measured in blood mononuclear cells. The protein levels of IL-4, IL-6, IL-13, IL-27, MIP-1ß, MCP-3, and GRO-α increased in both injured heart tissues and serum, while IFN-γ, IL-12P70, IL-2, IL-1ß, IL-18, TNF-α, IL-5, IL-9, IL-17A, IL-23, IL-10, eotaxin, MIP-1α, RANTES, MCP-1, and MIP-2 increased only in MI/R heart tissues in the day 7 and day 14 groups compared to the sham group. In serum, the IFN-γ, IL-23, and IL-10 levels were downregulated in the MI/R model at both day 7 and day 14 compared to the sham. Compared with the protein expressions in injured heart tissues at day 7, IFN-γ, IL-12P70, IL-2, IL-18, TNF-α, IL-6, IL-4, IL-5, IL-9, IL-17A, IL-23, IL-27, IL-10, eotaxin, IP-10, RANTES, MCP-1, MCP-3, and GRO-α were reduced, while IL-1ß and MIP-2 were elevated at day 14. IL-13 and MIP-1ß showed higher levels in the MI/R serum at day 14 than at day 7. mRNA levels of IL-4, IL-6, IL-13, and IL-27 were increased in the day 7 group compared to the sham, while MIP-1ß, MCP-3, and GRO-α mRNA levels showed no significant difference between the MI/R and sham groups in blood mononuclear cells. Multiple CD4+ T-cell-associated cytokines/chemokines were upregulated in the MI/R hearts at the chronic stage. These results provided important evidence necessary for developing future immunomodulatory therapies after MI/R.


Assuntos
Linfócitos T CD4-Positivos/metabolismo , Quimiocinas/metabolismo , Citocinas/metabolismo , Infarto do Miocárdio/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Animais , Quimiocina CCL3/sangue , Quimiocina CCL3/metabolismo , Interleucina-10/sangue , Interleucina-10/metabolismo , Interleucina-13/sangue , Interleucina-13/metabolismo , Interleucina-4/sangue , Interleucina-4/metabolismo , Interleucina-6/sangue , Interleucina-6/metabolismo , Leucócitos Mononucleares/metabolismo , Masculino , Camundongos , Infarto do Miocárdio/sangue , Traumatismo por Reperfusão Miocárdica/sangue
16.
J Transl Med ; 16(1): 120, 2018 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-29739434

RESUMO

BACKGROUND: Vaccines play increasingly important roles in cancer treatment due to their advantages of effective targeting and few side effects. Our laboratory has attempted to construct vaccines by conjugating TLR7 agonists with tumor-associated antigens. Furthermore, immunochemotherapy has recently become an appealing approach to cancer therapy. 5-fluorouracil (5-FU), a commonly used chemotherapeutic agent, can reportedly potently and selectively kill tumor-associated MDSCs in vivo. METHODS: Gastric cancer vaccines were synthesized by the covalent attachment of our TLR7 agonist with the gastric cancer antigen MG7-Ag tetra-epitope, leading to T7 - ML (linear tetra-epitope) and T7 - MB (branched tetra-epitope). Cytokines induced by the vaccines in vitro were assessed by ELISA. A tumor challenge model was created by treating BALB/c mice on either a prophylactic or therapeutic vaccination schedule. 5-FU was simultaneously applied to mice in the combination treatment group. CTL and ADCC activities were determined by the LDH method, while CD3+/CD8+, CD3+/CD4+ T cells and MDSCs were evaluated by flow cytometry. RESULTS: In vitro, rapid TNF-α and IL-12 inductions occurred in BMDCs treated with the vaccines. In vivo, among all the vaccines tested, T7 - MB most effectively reduced EAC tumor burdens and induced CTLs, antibodies and ADCC activity in BALB/c mice. Immunization with T7 - MB in combination with 5-FU chemotherapy reduced tumor sizes and extended long-term survival rates, mainly by improving T cell responses, including CTLs, CD3+/CD8+ and CD3+/CD4+ T cells. 5-FU also enhanced the T7 - MB efficiency by reversing immunosuppressive factors, i.e., MDSCs, which could not be validly inhibited by the vaccines alone. In addition, T7 - MB repressed tumor growth and immune tolerance when the therapeutic schedule was used, although the effects were weaker than those achieved with either T7 - MB alone or in combination with 5-FU on the prophylactic schedule. CONCLUSIONS: A novel effective gastric cancer vaccine was constructed, and the importance of branched multiple antigen peptides and chemical conjugation to vaccine design were confirmed. The synergistic effects and mechanisms of T7 - MB and 5-FU were also established, observing mainly T cell activation and MDSC inhibition.


Assuntos
Antineoplásicos/farmacologia , Vacinas Anticâncer/imunologia , Fluoruracila/farmacologia , Neoplasias Gástricas/imunologia , Receptor 7 Toll-Like/agonistas , Animais , Vacinas Anticâncer/química , Citocinas/metabolismo , Sinergismo Farmacológico , Epitopos/imunologia , Feminino , Camundongos Endogâmicos BALB C , Células Supressoras Mieloides/efeitos dos fármacos , Células Supressoras Mieloides/metabolismo , Vacinação
17.
Front Oncol ; 14: 1347282, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38595815

RESUMO

Given their good antitumor effects, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard first-line therapy for EGFR-sensitive mutations, including exon 19 deletions and exon 21 L858R mutations. EGFR fusion mutations and EGFR amplification are very rare in non-small cell lung cancer (NSCLC). We describe 2 patients with NSCLC harboring EGFR fusion mutations (EGFR-MACF1 and EGFR-GNAT3) combined with EGFR amplification. Both patients received EGFR-TKI treatment, and 1 of them showed an antitumor response.

18.
J Cardiothorac Surg ; 19(1): 278, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711077

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of intrapleural perfusion with hyperthermic chemotherapy (IPHC) in treating malignant pleural effusion (MPE). METHODS: PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), VIP Chinese Science and Technology Journal Full-text Database (VP-CSJFD), and Wanfang database were searched by computer from database establishment to January 17, 2024. Relevant randomized controlled articles with IPHC as the observational group and intrapleural perfusion chemotherapy (IPC) as the control group for MPE were included. Then, the methodological quality of the included articles was evaluated and statistically analyzed using Stata 16.0. RESULTS: Sixteen trials with 647 patients receiving IPHC and 661 patients receiving IPC were included. The meta-analysis found that MPE patients in the IPHC group had a more significant objective response rate [RR = 1.31, 95%CI (1.23, 1.38), P < 0.05] and life quality improvement rate [RR = 2.88, 95%CI (1.95, 4.24), P < 0.05] than those in the IPC group. IPHC and IPC for MPE patients had similar incidence rates of asthenia, thrombocytopenia, hepatic impairment, and leukopenia. CONCLUSION: Compared with IPC, IPHC has a higher objective response rate without significantly increasing adverse reactions. Therefore, IPHC is effective and safe. However, this study is limited by the quality of the literature. Therefore, more high-quality, multi-center, large-sample, rigorously designed randomized controlled clinical studies are still needed for verification and evaluation.


Assuntos
Hipertermia Induzida , Derrame Pleural Maligno , Humanos , Derrame Pleural Maligno/terapia , Hipertermia Induzida/métodos , Resultado do Tratamento , Quimioterapia do Câncer por Perfusão Regional/métodos , Quimioterapia do Câncer por Perfusão Regional/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos
19.
Adv Biol (Weinh) ; : e2400157, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39185769

RESUMO

FAM136A promotes the progression and metastasis of various tumors. However, there are few studies on the role of FAM136A in esophageal cancer (ESCA). The TCGA, GTEx, and GEO databases are employed to analyze the expression of FAM136A in ESCA, and qPCR and TMA experiments are performed for validation. Enrichment analyzes are performed to investigate the association of FAM136A expression with immune features, m6A modification, alternative splicing, cuproptosis, and the ceRNA network via bioinformatics analysis. FAM136A is highly expressed in ESCA and correlated with lymph node metastasis and overall survival (OS). Bioinformatics analysis suggested that FAM136A may participate in the following processes to promote ESCA development and progression: 1) Promotion of mast cells infiltration to influence the ESCA immune microenvironment, 2) HNRNPC upregulation to regulate m6A modification, 3) ALYREF upregulation to increase the occurrence of retained intron (RI) events, 4) CDK5RAP1 upregulation to achieve inhibition of tumor cell apoptosis, and 5) promotion of ESCA progression through the lncRNA SNHG15/hsa-miR-29c-3p/FAM136A ceRNA network. FAM136A is a potential biomarker for ESCA diagnosis and treatment response evaluation, and the underlying mechanisms may be associated with immune infiltration, m6A modification, alternative splicing, cuproptosis, and the ceRNA regulatory network.

20.
Front Oncol ; 14: 1420446, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39267852

RESUMO

Introduction: Esophagectomy patients who experience unplanned ICU admission (UIA) may experience a heavier economic burden and worse clinical outcomes than those who experience routine intensive care unit (ICU) admission. The aim of this study was to identify the risk factors for postoperative UIA in patients who underwent esophagectomy. Methods: We retrospectively included patients with esophageal cancer who underwent esophagectomy. The characteristics of postoperative UIA were described, and univariable and multivariable analyses were performed based on the logistic regression model. Furthermore, a recursive partitioning analysis was adopted to stratify the patients according to the risk of UIA. Results: A total of 628 patients were included in our final analysis, among whom 57 (9.1%) had an UIA. The patients in the UIA cohort had a higher rate of in-hospital mortality (P<0.001), longer hospital stay (P<0.001), and higher associated costs (P<0.001). Multivariable analysis showed that hybrid/open esophagectomy (OR=4.366, 95% CI=2.142 to 8.897, P<0.001), operation time (OR=1.006, 95% CI=1.002 to 1.011, P=0.007), intraoperative blood transfusion (OR=3.118, 95% CI=1.249 to 7.784, P=0.015) and the prognostic nutrition index (PNI) (OR=0.779, 95% CI=0.724 to 0.838, P<0.001) were independently associated with UIA. Conclusions: We identified several critical independent perioperative risk factors that may increase the risk of UIA following esophagectomy, and the above risk factors should be the focus of attention to reduce the incidence of postoperative UIA.

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