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1.
Immun Inflamm Dis ; 12(6): e1300, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38896093

RESUMO

OBJECTIVE: The sequelae of pelvic inflammatory disease (SPID) are major causes of secondary infertility. Modified Hongteng Baijiang decoction (MHTBD) has produced positive results in the treatment of patients with chronic pelvic inflammatory disease; however, its role in SPID remains elusive. Therefore, this study clarified the role of MHTBD in SPID pathogenesis. METHODS: The main components in MHTBD were analyzed by using liquid chromatography‒mass spectrometry (LC/MS). An SPID rat model was established, and the rats were treated with different doses of MHTBD (0.504 g of raw drug/kg, 1.008 g of raw drug/kg, and 2.016 g of raw drug/kg). Endometrial pinopodes were observed via scanning electron microscopy, endometrial thickness and inflammatory cell infiltration were assessed via HE staining, and the expression of estrogen receptor (ER), progesterone receptor (PR), integrin ß3 (ITGB3), and CD31 in the endometrium was detected by using immunohistochemistry. Western blot analysis was used to detect the protein expression of LIF, JAK2, p-JAK2, STAT3, and p-STAT3 in the endometrium. Moreover, the changes in the gut microbiota were analyzed via 16S rRNA sequencing. RESULTS: MHTBD improved endometrial receptivity, attenuated endometrial pathologic damage, reduced inflammatory cell infiltration, decreased ER and PR expression in the endometrium, and promoted the expression of LIF, p-JAK2, and p-STAT3 in the endometrium (p < .05) in SPID rats. Additionally, MHTBD treatment affected the composition of the gut microbiota in SPID rats. Furthermore, MHTBD attenuated endometrial receptivity and pathological damage in SPID rats by promoting the LIF/JAK2/STAT3 pathway. CONCLUSION: MHTBD attenuates SPID in rats by promoting the LIF/JAK2/STAT3 pathway and improving the composition of the gut microbiota. MHTBD may be a valuable drug for SPID therapy.


Assuntos
Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Janus Quinase 2 , Doença Inflamatória Pélvica , Fator de Transcrição STAT3 , Transdução de Sinais , Animais , Feminino , Ratos , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Endométrio/patologia , Endométrio/metabolismo , Endométrio/efeitos dos fármacos , Endométrio/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Janus Quinase 2/metabolismo , Doença Inflamatória Pélvica/tratamento farmacológico , Doença Inflamatória Pélvica/microbiologia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Masculino
2.
3 Biotech ; 14(5): 134, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38665879

RESUMO

Tubal inflammation, endometritis, and uterine adhesions due to post-pelvic inflammatory disease (SPID) are important causes of infertility. Chronic endometritis (CE) belongs to SPID, which seriously affects women's reproductive health, quality of life, and family harmony, and is a hot and difficult problem in clinical research. The efficacy of Pen Yan Kang Fu Decoction (PYKFD) has been verified in long-term clinical practice for chronic endometritis infertility caused by the SPID. Numerous studies have confirmed that the LIF/JAK2/STAT3 signaling pathway is important in embryo implantation and development, and endometritis infertility is close to LIF/JAK2/STAT3. In vivo results showed that PYKFD increased endometrial receptivity, repaired uterine tissue damage, and regulates the expression of endometrial receptivity-related factors ER (estrogen receptor), PR (progesterone receptor), CD31, and integrin αvß3, and induced the transduction of LIF/JAK2/STAT3 signaling pathway. PYKFD can also regulate the expression of IL-6. The results of in vitro experiments showed that PYKFD regulates the behavior of rat endometrial epithelial cells (REECs) involving LIF. In conclusion, PYKFD can improve endometrial receptivity and promote endometrial repair by LIF/JAK2/STAT3 signaling pathway. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03981-0.

3.
Plant Physiol ; 194(4): 2549-2563, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38235827

RESUMO

Gene duplications have long been recognized as a driving force in the evolution of genes, giving rise to novel functions. The soybean (Glycine max) genome is characterized by a large number of duplicated genes. However, the extent and mechanisms of functional divergence among these duplicated genes in soybean remain poorly understood. In this study, we revealed that 4 MYB genes (GmMYBA5, GmMYBA2, GmMYBA1, and Glyma.09g235000)-presumably generated by tandem duplication specifically in the Phaseoleae lineage-exhibited a stronger purifying selection in soybean compared to common bean (Phaseolus vulgaris). To gain insights into the diverse functions of these tandemly duplicated MYB genes in anthocyanin biosynthesis, we examined the expression, transcriptional activity, induced metabolites, and evolutionary history of these 4 MYB genes. Our data revealed that Glyma.09g235000 is a pseudogene, while the remaining 3 MYB genes exhibit strong transcriptional activation activity, promoting anthocyanin biosynthesis in different soybean tissues. GmMYBA5, GmMYBA2, and GmMYBA1 induced anthocyanin accumulation by upregulating the expression of anthocyanin pathway-related genes. Notably, GmMYBA5 showed a lower capacity for gene induction compared to GmMYBA2 and GmMYBA1. Metabolomics analysis further demonstrated that GmMYBA5 induced distinct anthocyanin accumulation in Nicotiana benthamiana leaves and soybean hairy roots compared to GmMYBA2 and GmMYBA1, suggesting their functional divergence leading to the accumulation of different metabolites accumulation following gene duplication. Together, our data provide evidence of functional divergence within the MYB gene cluster following tandem duplication, which sheds light on the potential evolutionary directions of gene duplications during legume evolution.


Assuntos
Genes myb , Glycine max , Glycine max/genética , Antocianinas/genética , Duplicação Gênica , Família Multigênica , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
4.
Inorg Chem ; 62(51): 21299-21308, 2023 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-38069807

RESUMO

Microflora within cancer cells plays a pivotal role in promoting metastasis of cancer. However, contemporary anticancer research often overlooks the potential benefits of combining anticancer and antibacterial agents. Consequently, a metal-organic framework Cu-Cip with cuproptosis and antibacterial properties was synthesized for cancer therapy. To enhance the anticancer effect of the material, Mn2+ was loaded into Cu-Cip, yielding Mn@Cu-Cip. The fabricated material was characterized using single-crystal X-ray diffraction, PXRD, and FT-IR. By interacting with overexpressed H2O2 to produce ROS and accumulating Cu ions in cancer cells, MOFs exhibited excellent anticancer performance. Moreover, the material displayed the function of damaging Staphylococcus aureus and Escherichia coli, revealing the admirable antibacterial properties of the material. In addition, the antibacterial ability could inhibit tumor cell migration. The Cu-based MOF revealed promising applications in the field of tumor treatment.


Assuntos
Estruturas Metalorgânicas , Neoplasias , Estruturas Metalorgânicas/farmacologia , Estruturas Metalorgânicas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Peróxido de Hidrogênio , Antibacterianos/farmacologia , Antibacterianos/química , Cristalografia por Raios X , Neoplasias/tratamento farmacológico
5.
Inorg Chem ; 62(44): 18128-18135, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37881839

RESUMO

Materials with enzyme-like activity have received a lot of attention in the field of tumor catalytic therapy. Here, biocompatible core-shell MOF CSMnP with two valence states of Mn ion, which could process chemodynamic therapy (CDT), was designed and synthesized. Besides, it could also promote a series of catalytic processes in the tumor microenvironment (TME). CSMnP catalyzed endogenous hydrogen peroxide (H2O2) to oxygen (O2) via catalase-like activity and then combined with the outer layer Mn(II)-PBC to convert O2 into superoxide radicals (•O2-), exhibiting oxidase-like activity. Besides, intracellular glutathione (GSH) could be effectively consumed through the glutathione oxidase-like activity of Mn3+. The occurrence of the cascade reactions effectively amplified the enzymatic production to enhance CDT. Furthermore, the therapeutic effect of CSMnP was improved through the loading of cationic drug DOX. The loading capacity was 11.10 wt %, which was 2.2 times that of Mn(III)-PBC (4.95 wt %), and the release of DOX showed a characteristic response. Therefore, the core-shell MOF with enzyme-like activity had a potential application for tumor combination therapy.


Assuntos
Peróxido de Hidrogênio , Neoplasias , Humanos , Catálise , Glutationa , Oxigênio , Neoplasias/tratamento farmacológico , Microambiente Tumoral
6.
Mol Breed ; 43(6): 43, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37313220

RESUMO

Seed oil content is one of the most important quantitative traits in soybean (Glycine max) breeding. Here, we constructed a high-density single nucleotide polymorphism linkage map using two genetically similar parents, Heinong 84 and Kenfeng 17, that differ dramatically in their seed oil contents, and performed quantitative trait loci (QTL) mapping of seed oil content in a recombinant inbred line (RIL) population derived from their cross. We detected five QTL related to seed oil content distributed on five chromosomes. The QTL for seed oil content explained over 10% of the phenotypic variation over two years. This QTL was mapped to an interval containing 20 candidate genes, including a previously reported gene, soybean RING Finger 1a (RNF1a) encoding an E3 ubiquitin ligase. Notably, two short sequences were inserted in the GmRNF1a coding region of KF 17 compared to that of HN 84, resulting in a longer protein variant in KF 17. Our results thus provide information for uncovering the genetic mechanisms determining seed oil content in soybean, as well as identifying an additional QTL and highlighting GmRNF1a as candidate gene for modulating seed oil content in soybean. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01384-2.

7.
Microbiol Spectr ; 11(3): e0380322, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37222613

RESUMO

Methods for efficient insoluble protein production require further exploration. PagP, an Escherichia coli outer membrane protein with high ß-sheet content, could function as an efficient fusion partner for inclusion body-targeted expression of recombinant peptides. The primary structure of a given polypeptide determines to a large extent its propensity to aggregate. Herein, aggregation "hot spots" (HSs) in PagP were analyzed using the web-based software AGGRESCAN, leading to identification of a C-terminal region harboring numerous HSs. Moreover, a proline-rich region was found in the ß-strands. Substitution of these prolines by residues with high ß-sheet propensity and hydrophobicity significantly improved its ability to form aggregates. Consequently, the absolute yields of recombinant antimicrobial peptides Magainin II, Metchnikowin, and Andropin were increased significantly when expressed in fusion with this refined version of PagP. We describe separation of recombinant target proteins expressed in inclusion bodies fused with the tag. An artificial NHT linker peptide with three motifs was implemented for separation and purification of authentic recombinant antimicrobial peptides. IMPORTANCE Fusion tag-induced formation of inclusion bodies provides a powerful means to express unstructured or toxic proteins. For a given fusion tag, how to enhance the formation of inclusion bodies remains to be explored. Our study illustrated that the aggregation HSs in a fusion tag played important roles in mediating its insoluble expression. Efficient production of inclusion bodies could also be implemented by refining its primary structure to form a more stable ß-sheet with higher hydrophobicity. This study provides a promising method for improvement of the insoluble expression of recombinant proteins.


Assuntos
Proteínas de Escherichia coli , Escherichia coli , Escherichia coli/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Peptídeos/química , Corpos de Inclusão , Peptídeos Antimicrobianos , Proteínas Recombinantes de Fusão/genética , Aciltransferases/análise , Aciltransferases/química , Aciltransferases/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo
8.
Am J Cancer Res ; 13(2): 498-508, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36895978

RESUMO

Since the approval by the Food and Drug Administration (FDA), ferumoxytol and other iron oxide nanoparticles (IONs) have been widely used as iron supplements for patients with iron deficiency. Meanwhile, IONs have also been used as contrast agents in magnetic resonance imaging and as drug carriers. Importantly, IONs have demonstrated a significant inhibitory effect on the growth of tumors, including hematopoietic and lymphoid tumors, such as leukemia. In this study, we further demonstrated the effect of IONs on inhibiting the growth of diffuse large B-cell lymphoma (DLBCL) cells by enhancing ferroptosis-mediated cell death. IONs treatment caused an accumulation of intracellular ferrous iron and the onset of lipid peroxidation in DLBCL cells as well as the suppressed expression of anti-ferroptosis protein Glutathione Peroxidase 4 (GPX4), thereby leading to increased ferroptosis. Mechanistically, IONs increased cellular lipid peroxidation through the generation of ROS via the Fenton reaction and regulating the iron metabolism-related proteins, such as ferroportin (FPN) and transferrin receptor (TFR), which elevated the intracellular labile iron pool (LIP). Hence, our findings suggest the potential therapeutic effect of IONs on the treatment of patients with DLBCL.

9.
Bioeng Transl Med ; 8(2): e10451, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36925711

RESUMO

Intracerebral hemorrhage (ICH) poses a great threat to human health because of its high mortality and morbidity. Neural stem cell (NSC) transplantation is promising for treating white matter injury following ICH to promote functional recovery. However, reactive oxygen species (ROS)-induced NSC apoptosis and uncontrolled differentiation hindered the effectiveness of the therapy. Herein, we developed a single-cell nanogel system by layer-by-layer (LbL) hydrogen bonding of gelatin and tannic acid (TA), which was modified with a boronic ester-based compound linking triiodothyronine (T3). In vitro, NSCs in nanogel were protected from ROS-induced apoptosis, with apoptotic signaling pathways downregulated. This process of ROS elimination by material shell synergistically triggered T3 release to induce NSC differentiation into oligodendrocytes. Furthermore, in animal studies, ICH mice receiving nanogels performed better in behavioral evaluation, neurological scaling, and open field tests. These animals exhibited enhanced differentiation of NSCs into oligodendrocytes and promoted white matter tract regeneration on Day 21 through activation of the αvß3/PI3K/THRA pathway. Consequently, transplantation of LbL(T3) nanogels largely resolved two obstacles in NSC therapy synergistically: low survival and uncontrolled differentiation, enhancing white matter regeneration and behavioral performance of ICH mice. As expected, nanoencapsulation with synergistic effects would efficiently provide hosts with various biological benefits and minimize the difficulty in material fabrication, inspiring next-generation material design for tackling complicated pathological conditions.

10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(4): 1116-1122, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-35981370

RESUMO

AbstractObjective: To explore the distribution characteristics and clinical significance of peripheral blood monocyte subgroups in patients with diffuse large Bcell lymphoma(DLBCL). METHODS: The percentage of peripheral blood monocyte subsets of 82 DLBCL patients (including 32 newly diagnosis, 29 remission and 21 relapse) and 30 healthy controls were detected by flow cytometry, and the correlation with the clinical characteristics and its diagnostic value of DLBCL were analyzed. RESULTS: The proportion of intermediate monocytes in patients with newly diagnosed DLBCL group was higher than that in healthy controls (t=5.888, P<0.01). The proportion in relapsed group was higher than those in newly diagnosed DLBCL group(t=2.106,P=0.04) and remission group (t=6.882, P<0.01), and the proportion of intermediate monocytes in newly diagnosed DLBCL group was higher than that in Remission group (t=3.969, P<0.01). With the increase of International Prognostic Index (IPI) score, the percentage of intermediate monocytes in patients with DLBCL increased (r=0.37). Furthermore, when the proportion of intermediate monocytes was 10.91% as the cutoff value, the sensitivity and specificity of the whole sample were 90.60% and 9100%, respectively. CONCLUSION: The disease progression is related to the increased intermediate monocytes, which can be used as a potential diagnostic index for DLBCL.


Assuntos
Linfoma Difuso de Grandes Células B , Monócitos , Protocolos de Quimioterapia Combinada Antineoplásica , Progressão da Doença , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Monócitos/patologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos
11.
Biomater Adv ; 138: 212940, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35913238

RESUMO

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease without effective treatment. Tofacitinib (TOF) is a JAK inhibitor that can be used for RA therapy, but it still faces the problems of nonspecific distribution and relatively low therapeutic effect. Herein, ICAM-1-modified TOF-loaded P(AN-co-AAm)-PEG micelles (AI-TM) were developed, which can result in an enhanced RA therapy when combining with microwave hyperthermia (MH). It was found that AI-TM could rapidly release the encapsulated TOF under a thermal condition of >43 °C, which was due to the fact that the polymeric micelles has an upper critical solution temperature (UCST) of 43 °C. AI-TM could specifically distribute into the inflamed joints of RA mice, which is associated with the high affinity between anti-ICAM-1 and overexpressed ICAM-1 receptors. Moreover, the combination of AI-TM and MH could result in a remarkably enhanced anti-rheumatic activity, which was related to the RA-targeted ability of AI-TM, the rapid TOF release under MH, and the combined effect between TOF and MH treatment. Our study definitely provides a novel strategy for effective treatment of RA.


Assuntos
Artrite Reumatoide , Hipertermia Induzida , Animais , Artrite Reumatoide/tratamento farmacológico , Camundongos , Micelas , Micro-Ondas , Piperidinas , Pirimidinas
12.
Lab Invest ; 102(12): 1377-1388, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35851856

RESUMO

In recent years, CC chemokine receptor 2 (CCR2) has been found to be involved in tumor growth, angiogenesis, epithelial mesenchymal transition, metastasis, and immune escape. CCR2 overexpression was first identified as a poor prognostic predictor in diffuse large B-cell lymphoma (DLBCL) in our published article, but the mechanisms involved remain unknown. In this work, we collected data from another 138 patients with DLBCL data and verified the CCR2 expression level and its relationship to clinicopathological characteristics. Furthermore, we explored the possible mechanisms via in vitro and in vivo experiments. We showed that CCR2 overexpression was an independent prognostic marker and predicted shorter overall survival (OS) and progression-free survival (PFS) in patients with DLBCL. Blockade of CCR2 expression with a CCR2 antagonist inhibited tumor cell proliferation, migration, and anti-apoptosis ability in vitro by affecting the PI3K/Akt signaling pathway and the p38 MAPK signaling pathway. Furthermore, administration of a CCR2 antagonist decreased tumor growth and dissemination of DLBCL cells and increased survival time in the xenograft model. Our study demonstrates that CCR2 expression plays an important role in the development of DLBCL by stimulating cell proliferation, migration, and anti-apoptosis. Therefore, the inhibition of CCR2 may be a potential target for anticancer therapy in DLBCL.


Assuntos
Linfoma Difuso de Grandes Células B , Receptores CCR2 , Humanos , Receptores CCR2/genética , Receptores CCR2/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Linfoma Difuso de Grandes Células B/metabolismo , Prognóstico , Processos Neoplásicos
13.
Biomater Sci ; 9(24): 8386-8395, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34787601

RESUMO

Methotrexate (MTX) as an anti-inflammatory drug for the treatment of rheumatoid arthritis (RA) through oral and injectable administration is still problematic in the clinic. Herein, a MTX-loaded thermal-responsible flexible liposome (MTFL) incorporated within a carbomer-based gel was prepared as a novel transdermal agent (MTFL/Gel) for effective treatment of RA. It was found that MTFL had an average size of approximately 90 nm, which could rapidly release the drug under thermal conditions. The prepared MTFL/Gel could remarkably increase the MTX skin permeation as compared with free MTX, which was possibly due to the deformable membrane of flexible liposomes. Moreover, the results suggested MTFL/Gel could lead to a remarkably enhanced RA treatment when in combination with microwave hyperthermia. The superior ability of MTFL/Gel to alleviate RA response was attributed to the excellent skin permeation, thermal-responsible drug release, and synergistic anti-arthritic effect of MTX chemotherapy and microwave-induced hyperthermia therapy. Overall, the MTFL/Gel with dual deformable and thermal-responsible performances could be used as a novel promising transdermal agent for enhanced treatment of RA.


Assuntos
Artrite Reumatoide , Hipertermia Induzida , Artrite Reumatoide/tratamento farmacológico , Humanos , Lipossomos , Metotrexato , Micro-Ondas
14.
Medicine (Baltimore) ; 100(31): e26744, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397815

RESUMO

ABSTRACT: Cured leprosy patients have special physical conditions, which could pose challenges for safety and immunogenicity after immunization. We performed an observational clinical study aimed to identify the safety and immunogenicity of influenza vaccine in cured leprosy patients. A total of 65 participants from a leprosarium were recruited into leprosy cured group or control group, and received a 0.5 ml dose of the inactivated split-virion trivalent influenza vaccine and a follow-up 28 days proactive observation of any adverse events. Hemagglutination and hemagglutination inhibition test was performed to evaluate serum antibody titer, flow cytometry was conducted to screen of cytokines level. The total rate of reactogenicity was 0.0% [0/41] in leprosy cured group and 37.5% [9/24] in control group. The seroconversion rate for H1N1 was difference between leprosy cured group and control group (41.83% vs 79.17%, P = .0082), but not for H3N2 (34.25% vs 50.00%, P = .4468). At day 0, leprosy cured group have relatively high concentration of interleukin-6, interleukin-10, tumor necrosis factor, interferon-γ, and interleukin-17 compared to control group. The interleukin-2 concentration increased 2 weeks after vaccination compared to pre-vaccination in leprosy cured group, but declined in control group (0.92 pg/ml vs -0.02 pg/ml, P = .0147). Leprosy cured group showed a more rapid down-regulation of interleukin-6 when influenza virus was challenged compared to control group (-144.38 pg/ml vs -11.52 pg/ml, P < .0001). Subgroup analysis revealed that the immunization administration declined interleukin-17 concentration in Tuberculoid type subgroup, but not in Lepromatous type subgroup or control group. Clinically cured leprosy patients are relatively safe for influenza vaccine. Leprosy cured patient have immune deficit in producing antibody. Interleukin-6 and interleukin-17 were 2 sensitive indicators in immune response for leprosy affected patients. The identification of indicators might be help management of leprosy and used as predictive markers in leprosy early symptom monitoring.


Assuntos
Imunidade/efeitos dos fármacos , Imunogenicidade da Vacina , Vacinas contra Influenza/normas , Hanseníase/tratamento farmacológico , Formação de Anticorpos/efeitos dos fármacos , Humanos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/imunologia , Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/uso terapêutico , Hanseníase/imunologia , Mycobacterium/efeitos dos fármacos , Mycobacterium/patogenicidade , Mycobacterium leprae/efeitos dos fármacos , Mycobacterium leprae/patogenicidade
15.
Front Neurol ; 12: 646990, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234732

RESUMO

Up to one-third (12-35%) of patients with aneurysmal subarachnoid hemorrhage experience intracerebral hematoma. Ruptured middle cerebral artery (MCA) aneurysm with hematoma is usually accompanied by progressive cerebral swelling with poor outcomes; however, it can be successfully treated by coil embolization and minimally invasive puncture and drainage. From February 2012 to March 2019, six surgeries for ruptured MCA aneurysms with intrasylvian hematoma were performed at our clinic. All patients had intracranial hematomas of <30 ml and GCS scores >8. The patients were treated by coil embolization and minimally invasive puncture and drainage. The aneurysms in all patients were completely embolized and the hematomas were mostly removed by minimally invasive puncture. The Glasgow outcome scale (GOS) scores of all patients were more than 4 at discharge when they discharged. Coil embolization and minimally invasive puncture and drainage are viable treatments for ruptured MCA aneurysms with hematomas, especially if the patient is too old, in a complicated state to undergo craniotomy, is unwilling to undergo craniotomy, or is at a greater risk of bleeding 3 days after surgery.

16.
J Cancer ; 12(1): 124-133, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391408

RESUMO

Background and Aims: Part 2 of our ongoing research with anti-angiogenic effects focuses on Wild chrysanthemum; a heat-clearing and detoxicating Traditional Chinese Medicine (TCM). We screened six heat-clearing and detoxicating TCM and noticed that wild chrysanthemum has a potent anti-angiogenic effect in zebrafish. This study aims to determine the genetic mechanisms underlying the anti-angiogenic effects of wild chrysanthemum. Methods: Wild chrysanthemum was decocted, concentrated, sieved and desiccated to attain the water extract. 200µg/mL wild chrysanthemum water extract (WCWE) was diluted in 0.1% dimethyl sulfoxide (DMSO) and given to zebrafish via fish water. 48h post-fertilization (hpf) fli1a-EGFP transgenic zebrafish were used to assay angiogenesis. mRNA-seq, qRT-PCR assay and a parallel reaction monitor (PRM) were carried out to reveal the underlying mechanisms. Results: WCWE showed a significant anti-angiogenic effect in zebrafish. The results of mRNA-seq showed that there were 1119 genes up-regulated and 1332 genes down-regulated by WCWE. The bioinformatic analysis based on mRNA-seq demonstrated that the proteasome signaling pathway was significantly down-regulated. The results of the qRT-PCR assay were consistent with those of the mRNA-seq assay. The results of the PRM assay showed that nine proteins involved in proteasome signaling and the protein expression level of ctnnb2 were significantly down-regulated. The results of the KEGG pathway analysis based on PRM assay demonstrated that WCWE may have an inhibitory action on the regulatory particle of the proteasome. Conclusion: Wild chrysanthemum has a significant anti-angiogenic effect in zebrafish and it may have an inhibitory action on the regulatory particle of the proteasome. The mechanisms underlying the anti-angiogenic effects of wild chrysanthemum may be related to the down-regulation of proteasome/ß-catenin signaling in zebrafish.

17.
Transl Pediatr ; 10(11): 3014-3022, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34976767

RESUMO

BACKGROUND: The choice of treatment methods for children with deep partial-thickness burn wounds (DPBWs) is an issue that requires careful consideration from surgeons. The purpose of this study was to evaluate the efficacy of precise partial scab removal (PPSR) in the treatment of DPBWs in children. METHODS: We retrospectively analyzed the clinical data of 78 children with DPBWs. The children were divided into a PPSR group (n=37) and a routine dressing change (RDC) group (n=41). In the PPSR group, an electric dermatome was used to cut the scab in the early post-injury period. The thickness scale of the electric dermatome was set to 0.1 mm. The scab was removed to the base with scattered bleeding points. There was still a small amount of necrotic tissue in the base of the wound. For the acellular dermal matrix, the first dressing change was about 1 week after surgery. The RDC group was given conventional wound-dressing treatment. The wound dressing was changed with epidermal growth factor, silver-zinc antibacterial cream, and dressing change. The frequency of dressing change was adjusted once a day or once every other day depending on the condition of wound secretions. The hospitalization time, wound-healing time, fever duration, antibiotic use time, number of subsequent operations, and overall hospitalization expenses were compared between the two groups. RESULTS: The wound-healing time of the PPSR group was 19.86±6.4 days, and the wound-healing time of the RDC group was 24.15±7.12 days (P=0.0068). The duration of fever in the PPSR group and RDC group was 2.62±1.99 and 4.44±3.10 days, respectively (P=0.0032). The antibiotic use time in the PPSR group and RDC group was 4.0±1.33 and 4.83±1.88 days, respectively (P=0.0292). The overall hospitalization cost of the PPSR group and RDC group was yuan renminbi ¥37,852.84±10,894.64 and ¥38,047.46±19,450.37, respectively (P=0.9573). CONCLUSIONS: PPSR can shorten wound-healing time, reduce the frequency of dressing changes, shorten the time of fever in children, lower the frequency of antibiotic use, and decrease number of dressing changes on the wound.

18.
Mol Med Rep ; 22(5): 4298-4306, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000200

RESUMO

The present study aimed to investigate the effects of sufentanil on sepsis-induced acute lung injury (ALI), and identify the potential molecular mechanisms underlying its effect. In order to achieve this, a rat sepsis model was established. Following treatment with sufentanil, the lung wet/dry (W/D) weight ratio was calculated. Histopathological analysis was performed via hematoxylin and eosin staining. Levels of inflammatory factors in bronchoalveolar lavage fluid were determined via ELISA. Furthermore, malondialdehyde (MDA) content and the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in tissue homogenates were assessed using commercial kits. Western blot analysis was performed to determine kininogen-1 (KNG1) protein expression. In addition, alveolar epithelial type II cells (AEC II) were stimulated with lipopolysaccharide (LPS) to mimic ALI. The levels of inflammation and oxidative stress were evaluated following overexpression of KNG1. Protein expression levels of nuclear factor-κB (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling were determined via western blot analysis. The results of the present study demonstrated that sufentanil alleviated histopathological injury and the W/D ratio in lung tissue. Following treatment with sufentanil, levels of inflammatory factors also decreased, accompanied by decreased concentrations of MDA, and increased activities of SOD, CAT and GSH-Px. Notably, KNG1 was decreased in lung tissues following treatment with sufentanil. Furthermore, overexpression of KNG1 attenuated the inhibitory effects of sufentanil on LPS-induced inflammation and oxidative stress in AEC II. Sufentanil markedly downregulated NF-κB expression, while upregulating Nrf2 and HO-1 expression levels, which was reversed following overexpression of KNG1. Taken together, the results of the present study suggested that sufentanil may alleviate inflammation and oxidative stress in sepsis-induced ALI by downregulating KNG1 expression.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/administração & dosagem , Cininogênios/metabolismo , Sepse/tratamento farmacológico , Sufentanil/administração & dosagem , Células A549 , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/imunologia , Animais , Anti-Inflamatórios/farmacologia , Líquido da Lavagem Broncoalveolar/imunologia , Modelos Animais de Doenças , Regulação para Baixo , Humanos , Lipopolissacarídeos/efeitos adversos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Sepse/complicações , Sepse/imunologia , Transdução de Sinais/efeitos dos fármacos , Sufentanil/farmacologia
19.
Carbohydr Polym ; 248: 116809, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32919542

RESUMO

The safe and effective delivery of anticancer drug molecules (e.g., doxorubicin [DOX]) into target sites is of great significance in cancer therapy. Recently, considerable attention has been devoted to non-covalently functionalized graphene as a potential anticancer delivery material. Herein, molecular dynamics simulations were performed to investigate the interaction mechanism between DOX and chitosan-decorated graphene with atomic details at the molecular level. The results demonstrated that the controllable loading and release of DOX by chitosan-decorated graphene may be achieved by adjusting the solution pH (the protonation state of chitosan) and the concentration of both DOX and chitosan molecules. In particular, the bare surface of graphene can be controlled by the aggregation and dispersion of chitosan, which further affects the adsorption and release of DOX molecules.


Assuntos
Quitosana/química , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Grafite/química , Simulação de Dinâmica Molecular , Adsorção , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinética , Doxorrubicina/química , Doxorrubicina/farmacocinética , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas
20.
IUBMB Life ; 72(8): 1780-1786, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32502299

RESUMO

The present study aimed to investigate the molecular mechanism and the effect of Saponin from Tupistra chinensis Baker (STCB) on the proliferation and apoptosis of ovarian cancer cells. To investigate the inhibitory effect of STCB on the proliferation of ovarian cancer cells, SKOV3 cells were cultured and the methyl thiazolyl tetrazolium assay was used. Flow cytometry was also used to analyze the cell cycle distribution and apoptotic rate. Ki-67, cyclin D1, cleaved caspase-3, cleaved caspase-9, ß-catenin, and c-Myc protein expressions were detected by western blot. Ovarian cancer cells were treated with STCB and Wnt pathway activator lithium chloride (LiCl). These methods were also used to determine the proliferation, cell cycle distribution, and apoptosis of ovarian cancer cells. In STCB-treated group, the proliferation inhibition and apoptosis rate, the proportion of G0-G1 phase, and the expression level of cleaved caspase-3 and 9 of ovarian cancer cells were significantly increased. Similarly, the expression of Ki-67, cyclin D1, ß-catenin, and c-Myc were significantly decreased (p < .05). The results also showed that in STCB-LiCl-treated group, while the proliferation inhibition rate of ovarian cancer cells, the proportion of G0-G1 cells, the expression level of cleaved caspase-3 and 9, and the apoptosis rate (p < .05) were significantly decreased, the expression level of Ki-67, cyclin D1, ß-catenin, and c-Myc was significantly increased. STCB induced G0-G1 phase arrest, inhibited cell proliferation, and promoted apoptosis of ovarian cancer cells by inhibiting Wnt/ß-catenin pathway.


Assuntos
Asparagaceae/química , Proliferação de Células/efeitos dos fármacos , Neoplasias Ovarianas/tratamento farmacológico , Saponinas/química , Apoptose/efeitos dos fármacos , Caspase 3/genética , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Ciclina D1/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Antígeno Ki-67/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Proteínas Proto-Oncogênicas c-myc/genética , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/genética
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