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High alkaline environment can lead to respiratory alkalosis and ammonia toxification to freshwater fish. However, the Amur ide (Leuciscus waleckii), which inhabits an extremely alkaline lake in China with titratable alkalinity up to 53.57â¯mM (pH 9.6) has developed special physiological and molecular mechanisms to adapt to such an environment. Nevertheless, how the Amur ide can maintain acid-base balance and perform ammonia detoxification effectively remains unclear. Therefore, this study was designed to study the ammonia excretion rate (Tamm), total nitrogen accumulation in blood and tissues, including identification, expression, and localization of ammonia-related transporters in gills of both the alkali and freshwater forms of the Amur ide. The results showed that the freshwater form Amur ide does not have a perfect ammonia excretion mechanism exposed to high-alkaline condition. Nevertheless, the alkali form of Amur ide was able to excrete ammonia better than freshwater from Amur ide, which was facilitated by the ionocytes transporters (Rhbg, Rhcg1, Na+/H+ exchanger 2 (NHE2), and V-type H+ ATPase (VHA)) in the gills. Converting ammonia into urea served as an ammonia detoxication strategy to reduced endogenous ammonia accumulation under high-alkaline environment.
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Amônia , Cipriniformes , Animais , Amônia/toxicidade , Amônia/metabolismo , Lagos , Proteínas de Membrana Transportadoras/metabolismo , Álcalis , Brânquias/metabolismoRESUMO
The typical pathological feature of aplastic anemia (AA) is the rise in the number of fat cells and the reduction of osteoblasts in bone marrow. However, both fat cells and osteobalsts in bone marrow are derived from the mesenchymal stem cells (MSCs). Generally, the adipogenic and osteogenic differentiation is a dynamic and balanceable process. The imbalance of the adipogenic and osteogenic differentiation may participate in the occurrence and progress of many diseases. Arsenic trioxide (ATO) could induce differentiation and apoptosis in tumor cells. In this study, Oil Red-O and Alizarin red were used to detect the adipogenic and osteogenic differentiation. The ability of adipogenic differentiation is much higher, whereas the osteogenic differentiation is much lower in the MSCs of AA patients compared with healthy controls. ATO inhibits adipogenic differentiation and promotes osteogenic differentiation in the MSC of AA patients. The expression of BMP4 is increased with ATO treatment. The ability of adipogenic differentiation is decreased, whereas the osteogenic differentiation is increased after transfection of BMP4 gene into the MSCs of AA patients. This study shows that ATO regulates the adipogenic and osteogenic differentiation balance of MSCs in AA, which provides a theoretical basis for the adjunctive therapy of ATO on AA. The BMP4 gene is involved in the ATO regulation of adipogenic and osteogenic differentiation balance, which provides a new target for the treatment of AA.
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Adipogenia/efeitos dos fármacos , Anemia Aplástica/patologia , Arsenicais/farmacologia , Proteína Morfogenética Óssea 4/genética , Diferenciação Celular/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Óxidos/farmacologia , Adipogenia/genética , Adulto , Trióxido de Arsênio , Estudos de Casos e Controles , Senescência Celular , Humanos , Células-Tronco Mesenquimais/citologia , Osteogênese/genéticaRESUMO
Lei's formula (LSF), a traditional Chinese herbal remedy, is recognized for its remarkable clinical effectiveness in treating osteoarthritis (OA). Despite its therapeutic potential, the exact molecular mechanisms underlying LSF's action in OA have remained enigmatic. Existing research has shed light on the role of the mTOR signaling pathway in promoting chondrocyte senescence, a central factor in OA-related cartilage degeneration. Consequently, targeting mTOR to mitigate chondrocyte senescence presents a promising avenue for OA treatment. The primary objective of this study is to establish LSF's chondroprotective potential and confirm its anti-osteoarthritic efficacy through mTOR inhibition. In vivo assessments using an OA mouse model reveal substantial articular cartilage degeneration. However, LSF serves as an effective guardian of articular cartilage, evidenced by reduced subchondral osteosclerosis, increased cartilage thickness, improved surface smoothness, decreased OARSI scores, elevated expression of cartilage anabolic markers (Col2 and Aggrecan), reduced expression of catabolic markers (Adamts5 and MMP13), increased expression of the chondrocyte hypertrophy marker (Col10), and decreased expression of chondrocyte senescence markers (P16 and P21). In vitro findings demonstrate that LSF shields chondrocytes from H2O2-induced apoptosis, inhibits senescence, enhances chondrocyte differentiation, promotes the synthesis of type II collagen and proteoglycans, and reduces cartilage degradation. Mechanistically, LSF suppresses chondrocyte senescence through the mTOR axis, orchestrating the equilibrium between chondrocyte anabolism and catabolism, ultimately leading to reduced apoptosis and decelerated OA cartilage degradation. LSF holds significant promise as a therapeutic approach for OA treatment, offering new insights into potential treatments for this prevalent age-related condition.
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Cartilagem Articular , Osteoartrite , Camundongos , Animais , Condrócitos/metabolismo , Peróxido de Hidrogênio/farmacologia , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Cartilagem Articular/metabolismoRESUMO
BACKGROUND: Our purpose was to compare the recurrence rate and other clinical outcomes of laparoscopic (LS) transabdominal preperitoneal (TAPP) inguinal hernia repair using n-butyl-2-cyanoacrylate (NBCA) for mesh fixation with those of no mesh fixation and mesh fixation with titanium spiral tacks (ST). METHODS: The medical records of patients who received LS TAPP inguinal hernia repair between 2009 and 2012 at our institution were reviewed. Patients were included if the received LS TAPP with either no mesh fixation, mesh fixation with NBCA only, fixation with ST only, or fixation with NBCA + ST. Outcome measures were operation time, postoperative length of stay, visual analogue scale (VAS) pain score 24 h after surgery, postoperative complications, and hernia recurrence. RESULTS: A total of 1,027 TAPP cases were included. In 552 cases, meshes were fixed with NBCA only, in 89 cases only ST were used, in 47 cases ST and NBCA were used, and in 339 cases meshes were not fixed. The groups were comparable with respect to demographic and clinical characteristics. No surgical complications occurred in any group. VAS pain scores were significantly lower in the nonfixation and NBCA only groups (1.4 ± 0.6 and 1.3 ± 0.6, respectively) than in the ST and NBCA + ST groups (2.2 ± 0.9 and 2.2 ± 0.7, respectively; P = 0.001). The mean follow-up duration was ~19 months. At the final follow-up, no wound infections or hernia recurrences had occurred in any of the groups. No occurrence of chronic pain was noted in the nonfixation and NBCA only groups, whereas two cases (2.2%) were noted in the ST group and one case (2.1%) in the NBCA + ST group (P = 0.005). CONCLUSIONS: The use of NBCA medical adhesive for noninvasive patch fixation in laparoscopic hernia repair (TAPP) is effective and safe.
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Embucrilato/uso terapêutico , Hérnia Inguinal/cirurgia , Herniorrafia/métodos , Laparoscopia/métodos , Adesivos Teciduais/uso terapêutico , Idoso , Índice de Massa Corporal , Comorbidade , Embucrilato/efeitos adversos , Feminino , Seguimentos , Herniorrafia/instrumentação , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/prevenção & controle , Recidiva , Estudos Retrospectivos , Telas Cirúrgicas , Adesivos Teciduais/efeitos adversos , Resultado do TratamentoRESUMO
Endometrial cancer (EC) is a malignancy of the inner epithelial lining of the uterus. While early-stage EC is often curable through surgery, the management of advanced, recurrent and metastatic EC poses significant challenges and is associated with a poor prognosis. Pyroptosis, an emerging form of programmed cell death, is characterized by the cleavage of gasdermin proteins, inducing the formation of extensive gasdermin pores in the cell membrane and the leakage of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18), consequently causing cell swelling, lysis and death. It has been found to be implicated in the occurrence and progression of almost all tumors. Recent studies have demonstrated that regulating tumor cells pyroptosis can exploit synergies function with traditional tumor treatments. This paper provides an overview of the research progress made in molecular mechanisms of pyroptosis. It then discusses the role of pyroptosis and its components in initiation and progression of endometrial cancer, emphasizing recent insights into the underlying mechanisms and highlighting unresolved questions. Furthermore, it explores the potential value of pyroptosis in the treatment of endometrial cancer, considering its current application in tumor radiotherapy, chemotherapy, targeted therapy and immunotherapy.
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Diabetic retinopathy (DR) is a prevalent complication of diabetes, significantly impacting patients' quality of life due to vision loss. No pharmacological therapies are currently approved for DR, excepted the drugs to treat diabetic macular edema such as the anti-VEGF agents or steroids administered by intraocular route. Advancements in research have highlighted the crucial role of early intervention in DR for halting or delaying disease progression. This holds immense significance in enhancing patients' quality of life and alleviating the societal burden associated with medical care costs. The non-proliferative stage represents the early phase of DR. In comparison to the proliferative stage, pathological changes primarily manifest as microangiomas and hemorrhages, while at the cellular level, there is a loss of pericytes, neuronal cell death, and disruption of components and functionality within the retinal neuronal vascular unit encompassing pericytes and neurons. Both neurodegenerative and microvascular abnormalities manifest in the early stages of DR. Therefore, our focus lies on the non-proliferative stage of DR and we have initially summarized the mechanisms involved in its development, including pathways such as polyols, that revolve around the pathological changes occurring during this early stage. We also integrate cutting-edge mechanisms, including leukocyte adhesion, neutrophil extracellular traps, multiple RNA regulation, microorganisms, cell death (ferroptosis and pyroptosis), and other related mechanisms. The current status of drug therapy for early-stage DR is also discussed to provide insights for the development of pharmaceutical interventions targeting the early treatment of DR.
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Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Humanos , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/etiologia , Retinopatia Diabética/metabolismo , Qualidade de Vida , Edema Macular/complicações , Neurônios/metabolismo , Pericitos/metabolismoRESUMO
OBJECTIVE: To study the effect of siRNA targeting ADAM17 (ADAM17-siRNA) on the proliferation of prostate cancer PC-3 cells. METHODS: After transfecting PC-3 cells with ADAM17-siRNA 1 and ADAM17-siRNA 2, we detected the expressions of ADAM17 mRNA and protein by RT- PCR and Western blotting, respectively. We measured the changes in the proliferation and DNA synthesis of PC-3 cells by MTT and bromodeoxyuridine (BrdU) incorporation assay, examined the cell cycle profile by flow cytometry, and determined the expressions of the genes associated with PC-3 cell proliferation by Western blotting. RESULTS: Both ADAM17-siRNA 1 and 2 effectively reduced the expressions of ADAM17 mRNA and protein in the PC-3 cells. Knockdown of ADAM17 with the two siRNAs significantly inhibited cell proliferation as compared with the control group (0.43 +/- 0.57 and 0.44 +/- 0.64 vs 0.80 +/- 0.51, P < 0.05) and down-regulated DNA synthesis (0.48 +/- 0.43 and 0.54 +/- 0.59 vs 0.79 +/- 0.72, P < 0.05). The cell cycle profile showed that the cell population of the G1 phase was markedly higher in both the ADAM17-siRNA groups than in the control ([61.83 +/- 2.41]% and [59.78 +/- 1.92]% vs [41.38 +/- 1.53]%, P < 0.05), but that of the S phase remarkably lower in the former two than in the latter ([23.64 +/- 2.56]% and [25.24 +/- 1.86]% vs [33.51 +/- 1.47]%, P < 0.05), with a concomitant decrease in the expression of the cell cycle protein cyclin D1 and increase in the cyclin-dependent kinase inhibitor p21. CONCLUSION: ADAM17-siRNA can effectively inhibit the proliferation of PC-3 cells by up-regulating cyclin D1 and down-regulating p21 protein, and ADAM17 has a potential value in the gene therapy of prostate cancer.
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Proteínas ADAM/metabolismo , Proliferação de Células , Neoplasias da Próstata/patologia , RNA Interferente Pequeno/genética , Proteínas ADAM/genética , Proteína ADAM17 , Linhagem Celular Tumoral , Ciclina D1/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Regulação para Baixo , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Interferência de RNA , RNA Mensageiro/genética , Transdução de Sinais , TransfecçãoRESUMO
BACKGROUND: An incisional hernia is a common complication of abdominal surgery. AIM: To evaluate the outcomes and complications of hybrid application of open and laparoscopic approaches in giant ventral hernia repair. METHODS: Medical records of patients who underwent open, laparoscopic, or hybrid surgery for a giant ventral hernia from 2006 to 2013 were retrospectively reviewed. The hernia recurrence rate and intra- and postoperative complications were calculated and recorded. RESULTS: Open, laparoscopic, and hybrid approaches were performed in 82, 94, and 132 patients, respectively. The mean hernia diameter was 13.11 ± 3.4 cm. The incidence of hernia recurrence in the hybrid procedure group was 1.3%, with a mean follow-up of 41 mo. This finding was significantly lower than that in the laparoscopic (12.3%) or open procedure groups (8.5%; P < 0.05). The incidence of intraoperative intestinal injury was 6.1%, 4.1%, and 1.5% in the open, laparoscopic, and hybrid procedures, respectively (hybrid vs open and laparoscopic procedures; P < 0.05). The proportion of postoperative intestinal fistula formation in the open, laparoscopic, and hybrid approach groups was 2.4%, 6.8%, and 3.3%, respectively (P > 0.05). CONCLUSION: A hybrid application of open and laparoscopic approaches was more effective and safer for repairing a giant ventral hernia than a single open or laparoscopic procedure.
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Twenty-one 4α-acyloxy-2-chloropodophyllotoxin derivatives (5a-u), whose C-4 spatial configuration was mainly stereocontrolled by the configuration of C-2 chlorine atom, were unexpectedly prepared by the reaction of 2-chloropodophyllotoxin with carboxylic acids in the presence of BF(3)·Et(2)O. Compared with ordinary esterifications of carboxylic acids mediated by the condensation agent, for example, N,N'-diisopropylcarbodiimide (DIC), the present method made the procedure for the preparation of 4α-acyloxy-2-chloropodophyllotoxins more convenient, practical and easy. Meanwhile, the insecticidal activity of compounds 5a-u was preliminarily evaluated against the pre-third-instar larvae of Mythimna separata Walker in vivo at the concentration of 1mg/mL.
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Boranos/química , Cloro/química , Inseticidas/síntese química , Larva/efeitos dos fármacos , Podofilotoxina/síntese química , Acilação , Animais , Inseticidas/química , Inseticidas/farmacologia , Estrutura Molecular , Mariposas , Podofilotoxina/química , Podofilotoxina/farmacologia , Estereoisomerismo , Fatores de TempoRESUMO
The Amur ide (Leuciscus waleckii) is a fish in the Cyprinidae family. Compared with other Amur ide living in freshwater ecosystems, the Amur ide population in Lake Dali Nor of China is famous for its high tolerance to the alkaline conditions of 54 mM (pH 9.6). Yet, surprisingly, the ionoregulatory mechanism responsible for this remarkable alkaline adaptation remains unclear. Therefore, this study sought to investigate how bicarbonate affects the acid-base balancing and ionoregulatory responses of this animal. Here, using a comparative approach, the alkali form of Amur ide and its ancestral freshwater form living in other freshwater basins were each exposed to 50 mM (pH 9.59 ± 0.09), a level close to the alkalinity of Lake Dali Nor, and their physiological (AE1) adjustment of ions and acid-base regulation were investigated. This study highlighted differences in blood pH and serum ions (e.g., Na+, K+, Cl-, and Ca2+), Na+/K+ ATPase (NKA) activity and its mRNA level, and mRNA expression of gill transporters (Na+/H+ exchanger member 2 and/or 3, Na+/ HCO 3 - cotransporter (NBC1), Cl-/ HCO 3 - exchanger, Na+/Cl- cotransporter (NCC), Na+/K+/2Cl- (NKCC1), SLC26A5, and SLC26A6) for alkalinity adaptation between the two forms of Amur ide differing in alkalinity tolerance. Specifically, close relationships among the serum Na+ and mRNA levels of NCC, NKCC1, and NHE, and also NKA and NBC1, in addition to serum Cl- and bicarbonate transporters (e.g., SLC26A5 and SLC26A6), characterized the alkali form of Amur ide. We propose that this ecotype can ensure its transepithelial Cl- and Na+ uptake/base secretions are highly functional, by its basolateral NKA with NBC1 and apical ionic transporters, and especially NCC incorporated with other transporters (e.g., SLC26). This suggests an evolved strong ability to maintain an ion osmotic and acid-base balance for more effectively facilitating its adaptability to the high alkaline environment. This study provides new insights into the physiological responses of the alkaline form of the Amur ide fish for adapting to extreme alkaline conditions. This information could be used as a reference to cultivating alkaline-tolerant fish species in abandoned alkaline waters.
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Leuciscus waleckii is a freshwater fish that is known to inhabit the Dali Nor Lake, Inner Mongolia, China. The water in this lake has an HCO3 -/CO3 2- concentration of 54 mM (pH 9.6) and a salinity of 0.6. The physiological mechanisms that allow this fish to tolerate these saline/alkaline conditions have yet to be elucidated. Transcriptional component analysis has shown that the expression levels of a large number of genes involved in the pathways responsible for osmo-ionoregulation and arachidonic acid metabolism pathway expression change significantly (p < 0.05) during the regulation of acid-base balance under high alkaline stress. In this study, we investigated the role of long non-coding RNAs (lncRNAs) during adaptation to high alkaline conditions. Fish were challenged to an NaHCO3-adjusted alkalinity of 0 mM, 30 mM (pH 9.44 ± 0.08), and 50 mM (pH 9.55 ± 0.06) for 20 days in the laboratory. Gill and kidney tissues were then collected for high-throughput sequencing assays. A total of 159 million clean reads were obtained by high-throughput sequencing, and 41,248 lncRNA transcripts were identified. Of these, the mean number of exons and the mean length of the lncRNA transcripts were 4.8 and 2,079 bp, respectively. Based on the analysis of differential lncRNA transcript expression, a total of 5,244 and 6,571 lncRNA transcripts were found to be differentially expressed in the gills and kidneys, respectively. Results derived from Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the coding genes were correlated with the lncRNA expression profiles. GO analysis showed that many lncRNAs were enriched in the following processes: "transporter activity," "response to stimulus," and "binding." KEGG analysis further revealed that metabolic pathways were significantly enriched. A random selection of 16 lncRNA transcripts was tested by RT-qPCR; these results were consistent with our sequencing results. We found that a large number of genes, with the same expression profiles as those with differentially expressed lncRNAs, were associated with the regulation of acid-base balance, ion transport, and the excretion of ammonia and nitrogen. Collectively, our data indicate that lncRNA-regulated gene expression plays an important role in the process of adaptation to high alkaline conditions in L. waleckii.
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The aim of this study is to investigate the role of anti-alpha-actinin antibodies in patients with new-onset systemic lupus erythematosus (SLE). Thirty-six patients with SLE, 16 of whom had lupus nephritis (LN), and 53 healthy controls were included. The clinical and laboratory parameters of patients were collected from medical records or by questionnaire. Serum anti-alpha-actinin Abs was measured by competitive enzyme linked immunosorbent assay (ELISA). Our results show that the OD value of serum anti-alpha-actinin Abs in SLE patients was significantly lower than that in normal controls (1.212 +/- 0.244 vs. 1.364 +/- 0.202, P = 0.002); seven of 36 SLE patients were seropositive for anti-alpha-actinin Abs, which was significantly higher than in normal controls (19.4 vs. 3.8%, P = 0.028). There were no significant differences of clinical parameters between the anti-alpha-actinin Abs-positive patients and the negative patients. The positive rate of the term urine casts, elevated IgM and IgA in anti-alpha-actinin Abs-positive patients were higher than that in the negative patients. The OD values of serum anti-alpha-actinin Abs negatively correlated with disease activity (R(s) = -0.352, P = 0.035). Anti-alpha-actinin Abs may be a useful marker of the disease activity of SLE; in addition, it may be used as a complementary parameter to differentiate LN from SLE without nephritis.
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Actinina/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Nefrite Lúpica/imunologia , Actinina/sangue , Adolescente , Adulto , Idoso , Análise de Variância , Biomarcadores , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Interleukin 17 (IL-17) is a Th17 cytokine associated with inflammation, autoimmunity and defense against some bacteria, it has been implicated in many chronic autoimmune diseases including psoriasis, multiple sclerosis and systemic sclerosis. However, whether IL-17 plays a role in the pathogenesis of systemic lupus erythematosus (SLE) remains unclear. In the present study, we aimed to investigate the serum IL-17 level in patients with SLE and it's associations with disease manifestations and activity. Fifty-seven patients with SLE and 30 healthy volunteers were recruited. Serum IL-17 levels were examined by enzyme linked immunosorbent assay (ELISA). Statistic analyzes were performed by SPSS 10.01. Results show that serum IL-17 levels were significantly elevated in SLE patients as compared with normal controls. Nevertheless, no associations of serum IL-17 level with clinical and laboratory parameters were found; no significant difference regarding serum IL-17 level between SLE patients with nephritis and those without nephritis was found; no significant difference was found between Less active SLE and More active SLE; Correlation analysis between serum IL-17 levels and SLEDAI showed no association. Taken together, our results indicate increased serum IL-17 levels in SLE patients, suggesting that this cytokine may trigger the inflammatory process in SLE. However, no associations of serum IL-17 level with disease manifestations were found. Therefore, further studies are required to confirm this preliminary data.
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Interleucina-17/sangue , Lúpus Eritematoso Sistêmico/sangue , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Neurofibroma can be a clinical manifestation of neurofibromatosis, which is a benign neurogenic tumor that occurs sporadically. Neurofibromas in the abdomen usually appear in the retroperitoneal space. Reports on neurofibromas in the abdominal wall are rare, and multiple recurrent neurofibromas in this area have not yet been reported. CASE SUMMARY: This is a case of a 73-year-old man who suffered from multiple recurrent neurofibromas in the abdominal wall for 16 years and received 13 surgical treatments. CONCLUSION: We need to pay due attention to its treatment, and primary surgery should be designed thoroughly.
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High temperature coal tar was used as raw materials, and was distilled to 280 degrees C for getting coal tar soft pitch. Then refined soft pitch was obtained by solvent extracting and subsequent settlement method. Its soft point was 32 degrees C; the group compositions consisted of 53.67% heptane soluble, 39.47% heptane insoluble but toluene soluble, 6.86% toluene insoluble and 0.06% quinoline insoluble. The relative average molecular weight was about 292. Its average molecular formula was C22.22 H16.32 N0.12 S0.06 O0.33; the total content of heteroatom was less than 1. IR analytic results showed that its heteroatom O existed in the R-O-R and Ar-O-R structure; its heteroatom N existed in the R-NH-R and -N=, with the latter being primary. Its average structure was obtained by improved Brown-Lander model: five-membered condensed rings. UV analysis indicated that the majority was linear arrangement, and the minority was surface arrangement; namely, the chemical structure of the samples was mainly the cata-condensed structure, while the minority was peri-condensation.
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This study aims to investigate the role of Antineutrophil cytoplasmic antibodies (ANCA) in patients with new-onset systemic lupus erythematosus (SLE). Sixty SLE patients, 28 of whom had lupus nephritis (LN), and 60 normal controls were enrolled; Serum ANCA was measured by enzyme linked immunosorbent assay (ELISA). The clinical and laboratory parameters of the patients were also recorded. Results show that twenty SLE patients were seropositive for ANCA, which was significantly higher than in normal controls. LN patients had significantly higher positive rate of ANCA than patients without nephritis. Compared with ANCA-negative patients, the ANCA-positive patients had significantly higher incidence of nerves system disorder, myocarditis, renal involvement and serositis. The positive rate of gamma-globulin, anti-dsDNA and anti-Sm antibodies were significantly higher in ANCA-positive patients. Elevated IgG and ESR, decreased serum C3/C4 appeared more often in ANCA-positive patients. In addition, serum ANCA level correlated positively with disease activity. Taken together, ANCA might be used as a potential complementary parameter to differentiate LN from SLE without nephritis. In addition, ANCA may serve as a useful marker of the disease activity of SLE.
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Anticorpos Anticitoplasma de Neutrófilos/sangue , Lúpus Eritematoso Sistêmico/imunologia , Nefrite Lúpica/imunologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Nefrite Lúpica/diagnóstico , Pessoa de Meia-Idade , Miocardite/etiologia , Miocardite/imunologia , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/imunologia , Serosite/etiologia , Serosite/imunologiaRESUMO
OBJECTIVE: To retrospectively analyze the immunophenotyping, fusion gene and gene mutation of 30 acute lymphoblastic leukemia (ALL) cases and to investigate the relationship between the analysis results and the clinical therapeutic effect and prognosis. METHODS: Thirty All phtients were collected from the First Hospital of Harbin, Institute of Hematology and Oncology Department of Pediatrics from August 2015 to June 2016. According to the classification of FAB standard, 27 cases were B system ALL, 3 cases were T system ALL. All patients were diagnosed by bone marrow cell morphology, immunophenotype, cytogenetics and molecular biology detetions, the differentiation antigens on membrane surface and in cytoplasm of ALL cells, and 43 kinds of fusion gene qualitative screeningï¼BCR-ABLï¼ AML1-ETO, PML-RARα and so onï¼ were qualitative screened and ALL gene mutationsï¼IKZF1, TP53, PAX5, JAK1, JAK2, CRLF2, PHF6, NOTCH1, FBXW7, PTENï¼were detected by next generation sequencing(NGS). RESULTS: (1) Among 30 ALL patients, the incidence of B-ALL(90.00%) was higher than that of T-ALL(10.00%). (2) 27 cases of B-ALL expressed CD19, CD22, CD10, CD34 and so on. CD19 and CD22 were the most diagnostic antigens of B-ALL. (3) 3 cases of T-ALL mainly expressed cCD3, CD7, CD10, cTDT and so on; cCD3 and CD7 were the most diagnostic antigens of T-ALL. (4) The quantitative screening of 30 cases of ALL 43 fusion genes found BCR-ABL,TEL-AML1 and E2A-PBX1, MLL-AF6, MLL-AF4, and SIL-TAL1 fusion gene was positive in 1 case each; NGS detection of gane mutations associated with ALL showed that: 3 cases of B-ALL found that TP53 mutation occured 3 casas of B-ALL, TET2 I1762V mutations in 1 cases, 3 patients (2 cases of T-ALL, 1 cases of B-ALL) showed NOTCH1 gene mutation. After a cycle of treatment, the efficacy of adult B-ALL treatment (28.57%) was significantly lower than that of child B-ALL (95.00%), and the survival rate of child B-ALL was significantly better than that of adult B-ALL until July 10, 2017, and the differences were significant. CONCLUSION: The immunophenotype technology of leukemia and molecular biology has an important guiding role in the diagnosis of leukemia, selection of treatment plan and evaluation of curative effect, and it is the complement of bone marrow cell morphology diagnosis.
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Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Imunofenotipagem , Proteínas de Fusão Oncogênica , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Estudos RetrospectivosRESUMO
OBJECTIVE: To construct the bait vector pGBKT7-TACEc (cytoplasmic tail of tumor necrosis factor-alpha converting enzyme) of Macthmaker GAL4 Two-hybrid System 3, and to test whether it has self-activation and toxic action. METHODS: TACEc gene was amplified by RT-PCR from the mouse testis, and the EcoRI and BamHI sites were introduced into it. The TACEc gene, after sequenced, was cloned into pGBKT7. Self-activation and toxic action of the recombination vector pGBKT7-TACEc was tested. RESULTS: The pGBKT7-TACEc vector was successfully constructed and proved of no self-activation and toxic action. CONCLUSION: The pGBKT7-TACEc can be applied to the screening of the mouse testis cDNA library in the yeast two-hybrid system.
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Proteínas ADAM/metabolismo , Testículo/metabolismo , Proteínas ADAM/genética , Proteína ADAM17 , Animais , Clonagem Molecular , DNA Complementar , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Plasmídeos , RNA/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Técnicas do Sistema de Duplo-Híbrido , Leveduras/metabolismoRESUMO
OBJECTIVE: To investigate the apoptosis-promoting effect of PDCD5 on human prostate cancer cells PC-3M-1E8. METHODS: PCI-neo and PCI-neo-PDCD5 were transfected into PC-3M-1E8 cells by Lipofectamine 2000, the viability of the cells was analyzed by MTT assay 16 hours after removal of the serum, and the apoptosis was determined by in situ end-labeling and electron microscopy. RESULTS: The viability and growing speed of the transfected cells were significantly decreased and their apoptotic indexes significantly increased as compared with the control group (P < 0.001). CONCLUSION: PDCD5 may significantly inhibit the in vitro growth and promote the apoptosis of human prostate cancer cells PC-3M-1E8.
Assuntos
Proteínas Reguladoras de Apoptose/fisiologia , Apoptose/fisiologia , Proteínas de Neoplasias/fisiologia , Apoptose/genética , Proteínas Reguladoras de Apoptose/genética , Linhagem Celular Tumoral , Humanos , Marcação In Situ das Extremidades Cortadas , Lipídeos/química , Masculino , Proteínas de Neoplasias/genética , Plasmídeos/química , Plasmídeos/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção/métodosRESUMO
OBJECTIVE: To detect the mutations of AML/MDS- related genes by using next generation sequencing (NGS), to analyze the mutation levels of each genes in the AML/MDS and the sensitivity of NGS, and to evaluate the feasibility of gene mutations for monitoring the MRD and predicating the progression of diseases. METHODS: The specimens were collected from primary AML (68 cases) and MDS (57 cases) patients from August 2015 to June 2016 in the Harbin Institute of Hematology and Oncology. The mutations of 22 related genes were detected by using AML/MDS-NGS chips. RESULTS: TET2 gene showed the highest mutation rate in AML (55.9%) and MDS (56.1%). The gene mutations were as follows: CEBPA (11.8%), DNMT3A (7.4%), C-KIT (7.4%) and FLT3-ITD (7.4%) in AML, and U2AF1 (10.5%) and SRSF2 (10.5%) in MDS. All the genes had specific mutation sites except TP53 and CEBPA. The mutations of FLT3, C-KIT and CEBPA became negative in the 5 AML patients in remission when compared with those at primary attack, but the mutation rate of TET2 gene was not obviously changed, whereas the mutation rate of the 5 MDS patients was not significantly changed. The new gene mutations appeared in 3 MDS patients with disease progression, but the mutation rate was not changed significantly in the disease progression. The gene mutation rate still has not been changed significantly even after remission. CONCLUSION: Both AML and MDS have their own specific mutated genes and sites. Some gene mutations, such as CEBPA, can be used as an effective indicator to monitoring MRD in AML patients, but those only used for the evaluation of the disease progression and prognosis in MDS patients.