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1.
J Ethnopharmacol ; 284: 114812, 2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-34752899

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Bai-Hu-Tang (BHT) is traditionally used to treat human and animal fever syndrome with four symptoms: large and vigorous pulse, large thirst, high sweat, and high heat. AIM OF THE STUDY: To investigate the mechanism of vasodilation regulation of Bai-Hu-Tang in primary vascular endothelial cells stimulated by lipopolysaccharide (LPS). MATERIALS AND METHODS: A hydrophilic concentrate of BHT was prepared, and the main components of mangiferin and timosaponin BⅡ were determined by HLPC analysis. The rabbit fever model was constructed by intravenous injection of LPS (15 µg/kg body weight), and BHT was gavaged to treat febrile rabbits. After treatment for 6 h, animal peripheral blood was collected, and serum was isolated for endothelin-1 (ET-1) and nitric oxide (NO) assays. Rabbit vascular endothelial cells (RVECs) were isolated and stimulated with 1 µg/mL LPS, and then inflammatory cells were treated with 125 or 250 µg/mL BHT for 24 h. The supernatant cytokines TNF-ɑ, IL-1ß, IL-6, and ET-1 were detected by ELISA kits. Gene expression levels of endothelin receptor type B (ETB receptor) were analysed by real-time polymerase chain reaction (RT-PCR), and protein expression levels of PI3K and Akt were detected by Western blot. A nitrite assay was used to measure intracellular nitric oxide (NO) production, and nitric oxide synthase (NOS) was measured by the T-NOS colorimetric method. RESULTS: Animal experiments demonstrated that BHT significantly restored ET-1 and NO in animal peripheral blood, which were disordered in LPS-induced fever rabbits. Moreover, a cytotoxicity assay demonstrated that BHT ≤700 µg/mL is innoxious to RVECs. BHT significantly repressed cellular TNF-α, IL-1ß, and ET-1, which were originally elevated by LPS in RVECs. Meanwhile, BHT elevated the gene expression level of the ETB receptor and promoted NOS and NO production in RVECs induced by LPS. CONCLUSION: BHT can inhibit excessive ET-1 secretion induced by LPS in vascular endothelial cells and activate the classic ET-1 signalling pathway to promote NO production, which may facilitate vasodilation of smooth muscle cells.

2.
Sci Total Environ ; : 151998, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34856281

RESUMO

With the rapid socio-economic development in China, poverty alleviation and the reduction of the environmental footprint in the plastic film mulching (PM) planting system have become key to sustainable agricultural production. Although many studies have evaluated the maize yield, agricultural economic benefits, and greenhouse gas (GHG) emissions associated with PM through small-scale field experiments, identifying suitable PM regions in combination with their demographic characteristics and the future development of such systems has received little attention. This study combines a Denitrification-Decomposition (DNDC) model and demographic characteristics to determine the optimum PM region in rainfed areas of the Loess Plateau in northwest China. The results demonstrated that PM produced a higher maize yield, agricultural net profit (ANP), and cost-benefit ratio compared to a control treatment (CK) without PM. An agricultural income far above the poverty level would assist in meeting the goals of alleviating poverty and building a prosperous society. In addition, the PM system produced more GHG emissions, but had a lower greenhouse gas intensity (GHGI) than CK under both low (200 kg N ha-1) and high (300 kg N ha-1) nitrogen (N) fertilizer rates. This study developed a framework to evaluate maize yield alongside economic and environmental indicators. We concluded that PM should be adopted in areas with precipitation less than 500 mm, and concentrated in the region with rainfall of 200-400 mm. The results provide a theoretical basis for the sustainable development of the PM maize planting system, and will contribute to the desired goal of environmentally sustainable agricultural production.

3.
Front Physiol ; 12: 749387, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858204

RESUMO

While RNAi is often heralded as a promising new strategy for insect pest control, a major obstacle that still remains is the efficient delivery of dsRNA molecules within the cells of the targeted insects. However, it seems overlooked that dsRNA viruses already have developed efficient strategies for transport of dsRNA molecules across tissue barriers and cellular membranes. Besides protecting their dsRNA genomes in a protective shell, dsRNA viruses also display outer capsid layers that incorporate sophisticated mechanisms to disrupt the plasma membrane layer and to translocate core particles (with linear dsRNA genome fragments) within the cytoplasm. Because of the perceived efficiency of the translocation mechanism, it is well worth analyzing in detail the molecular processes that are used to achieve this feat. In this review, the mechanism of cell entry by dsRNA viruses belonging to the Reoviridae family is discussed in detail. Because of the large amount of progress in mammalian versus insect models, the mechanism of infections of reoviruses in mammals (orthoreoviruses, rotaviruses, orbiviruses) will be treated as a point of reference against which infections of reoviruses in insects (orbiviruses in midges, plant viruses in hemipterans, insect-specific cypoviruses in lepidopterans) will be compared. The goal of this discussion is to uncover the basic principles by which dsRNA viruses cross tissue barriers and translocate their cargo to the cellular cytoplasm; such knowledge subsequently can be incorporated into the design of dsRNA virus-based viral-like particles for optimal delivery of RNAi triggers in targeted insect pests.

4.
Zhongguo Gu Shang ; 34(10): 928-3, 2021 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-34726021

RESUMO

OBJECTIVE: To evaluate the effect of degenerative scoliosis on the difficulty and efficacy of minimally invasive transforaminal lumbar interbody fusion(MIS-TLIF) in the treatment of lumbar spinal stenosis. METHODS: From September 2016 to September 2019, 52 patients with lumbar spinal stenosis treated by MIS-TLIF were retrospectively analyzed, including 16 males and 36 females, aged from 42 to 71(63.44±5.96) years old, the course of disease from 1.5 to 6.5 years, with an average of (3.69±1.10) years. All patients had lower extremity root pain or numbness, 41 patients had intermittent claudication. There were 31 cases of L4, 5 and 21 cases of L5S1. There were 18 cases in scoliosis group, lumbar spinal stenosis combined withdegenerative scoliosis, and 34 cases in stenosis group, lumbar spinal stenosis alone. The perioperative data and postoperative complications were recorded, the postoperative interbody fusion was evaluated by CT, and the clinical outcomes were evaluated by VAS score, Oswestry Disability Index (ODI). RESULTS: All patients were followed up for 12 to 36 months, with an average of (19.58±5.33) months. The operation time and intraoperative bleeding in stenosis group were better than those in scoliosis group (P<0.05). There were no significant differences in postoperative drainage volume, postoperative Hb, CRP, postoperative landing time, discharge time, VAS score at discharge and follow-up, ODI score at 3 months and follow up, postoperative complications and interbody fusion rate between two groups (P>0.05). CONCLUSION: For patients with lumbar spinal stenosis undergoing MIS-TLIF, degenerative scoliosis can lead to prolonged operation time and increased bleeding. However, it has no significant effect on therelief of postoperative symptoms, postoperative complications and the recovery of lumbar function.


Assuntos
Escoliose , Fusão Vertebral , Estenose Espinal , Adulto , Idoso , Feminino , Humanos , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Estudos Retrospectivos , Escoliose/cirurgia , Estenose Espinal/cirurgia , Resultado do Tratamento
5.
Front Nutr ; 8: 709211, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746201

RESUMO

Background and Aims: Sarcopenia is negatively associated with clinical outcomes. However, the definitions of sarcopenia are inconsistent across international consensuses. Thus, the purpose of this study is to compare the impact of the basic definition components of sarcopenia and their combinations in post-operative complications and overall survival, aiming to find the best sarcopenia definition to stratify the prognosis in an Asian population. Methods: A total of 1,307 patients who underwent curative surgery for gastric cancer from July 2014 to May 2019 were prospectively included. The basic sarcopenia components were measured pre-operatively, including low skeletal muscle mass index (LSMI), low skeletal muscle radiodensity (LSMD), low handgrip strength (LHGS), and low gait speed (LGS). Among them, LSMI and LSMD were measured using a CT post-processing software, LHGS was measured using an electronic hand dynamometer, and LGS was represented by a 6-m walk speed. Results: For the single basic component, the muscle function parameters (LHGS or LGS) but not the muscle composition parameters (LSMI or LSMD) showed associations with post-operative complications and mortality. For the combination of the basic combinations, all statistically significant combinations included at least one muscle function parameter. The combination of muscle composition (LSMI or LSMD) and muscle function (LHGS or LGS) had a significantly higher area under the curve in the prediction of post-operative complications compared with the combinations of two muscle function parameters (LSMI plus LSMD) or two muscle composition parameters (LHGS plus LGS). Conclusions: Compared with muscle composition parameters (LSMI and LSMD), muscle function parameters (LHGS and LGS) are better predictors of post-operative complications and overall survival, which should be considered as the principal determinant in the sarcopenia definition. The definition of sarcopenia consists of muscle function (LHGS or LGS) and muscle composition (LSMI or LSMD) separately, which is better than the combination of the two muscle function parameters (LHGS plus LGS) or two muscle composition parameters (LSMI plus LSMD).

6.
Ann Surg Oncol ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34797480

RESUMO

BACKGROUND: Sarcopenia and cachexia are two predictors of adverse clinical outcomes, but they are partly overlapping. We aimed to compare the characteristics and prognostic value of cachexia and sarcopenia in patients after gastrectomy. METHODS: From 2014 to 2019, a total of 1215 gastric cancer patients were enrolled. Cachexia and sarcopenia were diagnosed according to the most recent consensus definitions. Baseline characteristics and clinical outcomes were compared between the two groups. Risk factors of survival were evaluated by Cox regression analysis. RESULTS: Of all patients, 26.5% were diagnosed with cachexia and 19.8% were diagnosed with sarcopenia. Sarcopenia was more prevalent in elderly patients, while cachexia was prone to occur in patients with TMN stage III. Survival curves showed that sarcopenia had adverse effects in patients with TMN stage I and II-III, while cachexia was only associated with poor survival at stages II-III. For the entire cohort, both cachexia and sarcopenia were adverse factors for prognosis. However, for stage I patients, sarcopenia was an independent predictor for overall survival (OS) (HR = 4.939, P < 0.001) and disease-free survival (DFS) (HR = 4.256, P < 0.001), but not cachexia; for stage II-III patients, cachexia was an independent predictor for OS (HR = 1.538, P < 0.001) and DFS (HR = 1.473, P = 0.001), but not sarcopenia. CONCLUSIONS: Sarcopenia and cachexia have different clinical characteristics and prognostic values. For patients with early stage gastric cancer, detection for sarcopenia was more meaningful than cachexia. However, the prognostic significance of cachexia exceeded sarcopenia in advanced cancer.

8.
Plant Direct ; 5(10): e345, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34622120

RESUMO

Developmental transitions are typically tightly controlled at the transcriptional level. Two of these transitions involve the induction of the embryo maturation program midway through seed development and its repression during the vegetative phase of plant growth. Very little is known about the factors responsible for this regulation during early embryogenesis, and only a couple of transcription factors have been characterized as repressors during the postgerminative phase. Arabidopsis 6b-INTERACTING PROTEIN-LIKE1 (ASIL1), a trihelix transcription factor, has been proposed to repress maturation both embryonically and postembryonically. Preliminary data also suggested that its closest paralog, ASIL2, might play a role as well. We used a transcriptomic approach, coupled with phenotypical observations, to test the hypothesis that ASIL1 and ASIL2 redundantly turn off maturation during both phases of growth. Our results indicate that, contrary to what was previously published, neither of the ASIL genes plays a role in the regulation of maturation, at any point during plant development. Analyses of gene ontology (GO)-enriched terms and published transcriptomic datasets suggest that these genes might be involved in responses during the vegetative phase to certain biotic and abiotic stresses.

9.
iScience ; 24(10): 103101, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34622156

RESUMO

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that would permanently damage the affected joints. Unfortunately, a large proportion of RA patients fail to respond adequately to current treatments. Here, repurposing hemin and its ultra-long-acting formulation were explored for the effective treatment of RA in animal models. We provided evidence that hemin prevented the onset and ameliorated the clinical course of RA. Notably, hemin treatment rescued the dysregulated gene expression in animal models of RA, resulting in attenuation of Th1/Th17 cell-mediated responses and proinflammatory cytokines. Moreover, we further formulated hemin into the in-situ forming implant, and a single injection of the ultra-long-acting hemin exerted potent disease-modifying effects for at least six weeks with a remarkable dose reduction. Taken together, given the potent anti-inflammatory and immunosuppressive effects, the once-monthly hemin injection holds promise for rapid clinical translation, and represents a potential strategy to treat RA and possibly other autoimmune diseases.

10.
J Pharm Biomed Anal ; 206: 114390, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34600174

RESUMO

XL092 is a novel tyrosine kinase inhibitor with antitumor activity. The goal of this study was to evaluate its in vitro metabolism of XL092 using rat and human liver microsomes and hepatocytes. The metabolites were identified using ultra-high performance liquid chromatography combined with high resolution mass spectrometry. The structure of the metabolite was characterized by accurate mass, elemental composition and MS/MS spectra. The cytochrome P450 enzyme responsible for XL092 metabolism was evaluated by using recombinant human CYP450 enzymes. A total of 26 metabolites, including 21 phase I metabolites and 5 phase II metabolites, were characterized. XL092 was metabolized mainly through oxidative defluorination, hydroxylation, N-demethylation, O-demethylation, amide hydrolysis, N-dealkylation, O-dealkylation, N-oxygenation and glucuronidation. Among these metabolites, M10 (oxidative defluorination) and M17 (hydroxylation) were the most abundant metabolites. CYP3A4 and CYP2D6 were the major enzymes responsible for XL092 metabolism. Taken together, this study for the first time evaluated the in vitro metabolic profiles of XL092 in rat and human, which is of great help for us to investigate the XL092 pharmacokinetic and toxicity assessment and to predict the in vivo human metabolism.


Assuntos
Microssomos Hepáticos , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida de Alta Pressão , Humanos , Hidroxilação , Microssomos Hepáticos/metabolismo , Inibidores de Proteínas Quinases/metabolismo , Ratos
11.
Theranostics ; 11(19): 9605-9622, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646389

RESUMO

Rationale: Recurrent and metastatic cancers often undergo a period of dormancy, which is closely associated with cellular quiescence, a state whereby cells exit the cell cycle and are reversibly arrested in G0 phase. Curative cancer treatment thus requires therapies that either sustain the dormant state of quiescent cancer cells, or preferentially, eliminate them. However, the mechanisms responsible for the survival of quiescent cancer cells remain obscure. Methods: Dual genome-editing was carried out using a CRISPR/Cas9-based system to label endogenous p27 and Ki67 with the green and red fluorescent proteins EGFP and mCherry, respectively, in melanoma cells. Analysis of transcriptomes of isolated EGFP-p27highmCherry-Ki67low quiescent cells was conducted at bulk and single cell levels using RNA-sequencing. The extracellular acidification rate and oxygen consumption rate were measured to define metabolic phenotypes. SiRNA and inducible shRNA knockdown, chromatin immunoprecipitation and luciferase reporter assays were employed to elucidate mechanisms of the metabolic switch in quiescent cells. Results: Dual labelling of endogenous p27 and Ki67 with differentiable fluorescent probes allowed for visualization, isolation, and analysis of viable p27highKi67low quiescent cells. Paradoxically, the proto-oncoprotein c-Myc, which commonly drives malignant cell cycle progression, was expressed at relatively high levels in p27highKi67low quiescent cells and supported their survival through promoting mitochondrial oxidative phosphorylation (OXPHOS). In this context, c-Myc selectively transactivated genes encoding OXPHOS enzymes, including subunits of isocitric dehydrogenase 3 (IDH3), whereas its binding to cell cycle progression gene promoters was decreased in quiescent cells. Silencing of c-Myc or the catalytic subunit of IDH3, IDH3α, preferentially killed quiescent cells, recapitulating the effect of treatment with OXPHOS inhibitors. Conclusion: These results establish a rigorous experimental system for investigating cellular quiescence, uncover the high selectivity of c-Myc in activating OXPHOS genes in quiescent cells, and propose OXPHOS targeting as a potential therapeutic avenue to counter cancer cells in quiescence.

12.
BMC Psychiatry ; 21(1): 523, 2021 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-34686160

RESUMO

BACKGROUND: The behavioral characteristics of children with autism spectrum disorder (ASD) are not only affected by their disease, but also by their parenting environment. HR-ASD has the risk of developing internalization and externalization problems. How the early development of these behavioral problems is affected by parent-child interaction is worth exploring. We tested whether parent-child interactions and parenting characteristics were associated with behavioural problems during the infant periods. METHODS: This study collected data from 91 infants at high risk for ASD and 68 matched typically developing (TD) infants, about their internalizing and externalizing behavioural problems and engagement states (i.e. positive, negative, and parent-child interactions), using free play paradigm. Parent measures were assessed using the Broad Autism Phenotypic Questionnaire (BAPQ) and Parenting Stress Index Short Form (PSI-SF) questionnaire. The core symptoms of ASD were assessed using the the Autism Diagnostic Observational Schedule (ADOS). RESULTS: During free play, infants in the HR-ASD group showed more internalizing (P < 0.001) and externalizing (P < 0.05) behaviours and less positive engagement (P < 0.01) than the TD group. In the regression analysis, we found that parenting stress had an impact on the infants' externalizing behaviours (△R2 = 0.215). Parent negative engagement had an impact on the infants' internalizing behaviours (△R2 = 0.451). CONCLUSIONS: The present study revealed that children at high risk for ASD exhibited more severe internalizing and externalizing behavioural problems than TD group. The parent negative engagement is associated with behavioural problems. The findings on the contribution of parents' factors to behavioural problems suggests that the parenting stress and parent-child interactions are important factors for mitigating behavioural problems.

14.
Front Plant Sci ; 12: 681490, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34567020

RESUMO

Crop plants grow, and then, they allocate resources to different structures, including seeds and fruits, which represent yield in most crops. We define the yield stability of a genotype as its ability to reduce the effects of temporal variation in resources and conditions on yield production, and we argue that yield stability can be understood in terms of two processes: (1) crop survival and growth (biomass production): the ability of the crop plants to survive and produce biomass under the range of conditions to which it is exposed and (2) the pattern of allocation of this biomass to yield across this range of conditions. Plant breeders and crop physiologists have focused on (1), but much less attention has been paid to (2). We hypothesize that (2) is primarily the result of reproductive allometry: the quantitative relationship between vegetative and reproductive biomass. Ecological theory and the allometric models we present predict a tradeoff between (a) the ability of a genotype to produce yield over a wide variety of conditions and (b) its ability to produce very high yields under optimal or near-optimal conditions. We reanalyze the data from two recent studies, and the results are consistent with this hypothesis. Yield stability in crops corresponds to bet-hedging in evolutionary ecological theory. It is the most appropriate strategy for smallholder farmers in developing countries, a group that comprises most of the farmers in the world. Researchers and crop breeders need to rethink their objectives if they want to develop optimal varieties for these farmers.

15.
Nanomaterials (Basel) ; 11(9)2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34578619

RESUMO

Functionalized carbon nanomaterials are considered to be an efficient modifier for ultrafiltration membranes with enhanced performance. However, most of the reported carbon nanomaterials are derived from unsustainable fossil fuels, while an extra modification is often essential before incorporating the nanomaterials in membranes, thus inevitably increasing the cost and complexity. In this work, novel functionalized biomass-based carbon nanoparticles were prepared successfully from agricultural wastes of corn stalks through simple one-step acid oxidation method. The obtained particles with the size of ~45 nm have excellent dispersibility in both aqueous and dimethyl formamide solutions with abundant oxygen-containing groups and negative potentials, which can endow the polysulfone ultrafiltration membranes with enhanced surface hydrophilicity, larger pore size, more finger-like pores, and lower surface roughness. Therefore, the separation and anti-fouling performance of membranes are improved simultaneously. Meanwhile, the addition of 0.4 wt% nanoparticles was proved to be the best condition for membrane preparation as excess modifiers may lead to particle aggregation and performance recession. It is expected that these biomass-based carbon nanoparticles are potential modifying materials for improving the separation performance and anti-fouling property of the membranes with great simplicity and renewability, which pave a new avenue for membrane modification and agricultural waste utilization.

16.
Front Cell Infect Microbiol ; 11: 703259, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34557425

RESUMO

Given that only a small percentage of human papillomavirus (HPV)-positive women develop cancer, HPV is necessary but insufficient for carcinogenesis. Mucosally transmitted viral cofactors appear to contribute to HPV-related cervical cancer, such as Epstein-Barr virus (EBV), but previous studies have shown inconsistent outcomes. The exact role of EBV in cervical cancer remains unclear, and more studies are needed to determine its involvement. In this study, we describe the prevalence of EBV and HPV coinfection in HIV-positive women and explore how abnormal host immune status induced by viral coinfections modulates epithelial gene expression. We found a significant correlation between EBV-HPV coinfection and the incidence of high-grade cervical intraepithelial neoplasia (CIN2+). RNA sequencing indicated that CIN tissues coinfected with EBV and HPV led to significant changes in the gene expression of epithelial differentiation and development compared to normal tissues with HPV infection alone. In particular, several differentially expressed genes (DEGs) are closely associated with cancer, such as CACNG4, which was confirmed to be upregulated at both the mRNA and protein levels. Therefore, these findings provide some evidence that EBV may act as a cofactor or mediator in HPV-related cervical cancer. Specific genes or proteins, such as CACNG4, may serve as biomarkers that can risk stratify patients based on pathological changes in the cervix.


Assuntos
Alphapapillomavirus , Neoplasia Intraepitelial Cervical , Coinfecção , Infecções por Vírus Epstein-Barr , Infecções por HIV , China/epidemiologia , DNA Viral , Infecções por Vírus Epstein-Barr/complicações , Feminino , Infecções por HIV/complicações , Herpesvirus Humano 4/genética , Humanos , Papillomaviridae/genética
17.
Eur J Surg Oncol ; 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34420825

RESUMO

BACKGROUND: The relationships between sarcopenia and postoperative outcomes in patients with early-stage gastric cancer who undergo radical gastrectomy is unclear. We aimed to investigate the predictive value of sarcopenia on adverse outcomes for stage I gastric cancer. METHODS: The clinical data of patients who underwent radical gastrectomy for stage I gastric cancer between July 2013 and May 2019 were prospectively collected. Basic sarcopenia components were measured preoperatively. Univariate and multivariate analyses were conducted to evaluate the risk factors for short- and long-term outcomes. RESULTS: A total of 507 patients with early-stage gastric cancer were included in the study, and 73 (14.4%) patients were diagnosed as sarcopenia. Patients with sarcopenia had significantly higher incidence of postoperative complications (32.9% vs. 17.5%, P = 0.002), longer postoperative hospital stays (13 days vs. 12 days, P < 0.001), higher hospitalization costs (65210 yuan vs. 55197 yuan, P < 0.001) and one-year mortality (8.2% vs. 1.8%, P = 0.002). During the median follow-up time of 38.8 months, 12 (16.4%) patients dead in the sarcopenic group and 25 (5.8%) patients dead in the non-sarcopenic group. Sarcopenia was an independent risk factor for both short- and long-term clinical outcomes. Moreover, we found that low muscle quantity and low handgrip strength mediated the adverse impacts of sarcopenia on postoperative complications while low muscle quality mediated the adverse impacts of sarcopenia on overall survival. CONCLUSION: Sarcopenia was strongly associated with worse short- and long-term clinical outcomes in patients with stage I gastric cancer who undergo radical gastrectomy.

18.
Hematology ; 26(1): 543-551, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34348586

RESUMO

Objectives: Chronic myeloid leukemia (CML) is a malignant tumor of the blood system. Gö6976, as a type of indolocarbazole and shows strong antitumor effects, but there have been no reports on the effect of Gö6976 on CML. The objectives of this research were: (1) to explore the impact of Gö6976 on CML in vitro and in vivo; and (2) to explore the drug toxicity of Gö6976 to normal cells and animals.Methods:K562 cells and CML mice were used to explore the effect of Gö6976 on CML. Peripheral blood mononuclear cells (PBMCs), CD34+ cells, and healthy mice were used to explore the drug toxicity of Gö6976.Results: Cell experiments showed that Gö6976 could inhibit the proliferation of K562 cells and enhance the inhibitory effects of imatinib at 5 µM and 10 µM, but it had little effect on CD34+ cells or PBMCs at concentrations less than 5 µM. Animal experiments showed that 2.5 mg/kg Gö6976 could effectively inhibit the development of CML in mice, and it had almost no effects on healthy mice at 2.5 mg/kg and 10 mg/kg.Discussion: Because of the direct inhibitory effect of Gö6976 on CML and its pharmacological enhancement effect on imatinib, it is foreseeable that Gö6976 could become a new type of anti-CML medicine. And the further research is needed.Conclusion: Our findings verified that Gö6976 could effectively inhibit CML in vitro and in vivo, and it is almost nontoxic to hematopoietic cells, immune cells, and healthy mice.


Assuntos
Carbazóis/farmacologia , Proliferação de Células/efeitos dos fármacos , Mesilato de Imatinib/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Animais , Carbazóis/agonistas , Agonismo de Drogas , Humanos , Mesilato de Imatinib/agonistas , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NOD , Camundongos SCID , Ensaios Antitumorais Modelo de Xenoenxerto
19.
BMC Endocr Disord ; 21(1): 154, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344344

RESUMO

BACKGROUND: Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare monogenic inherited disease caused by mutations of the autoimmune regulator gene (AIRE). The three major components of this syndrome are chronic mucocutaneous candidiasis, hypoparathyroidism and adrenocortical insufficiency. CASE PRESENTATION: We report a 20-year-old male who was clinically diagnosed with APS-1 at the age of 15. He was admitted to our department this time for suffering from polyuria and polydipsia for 6 months and was finally diagnosed with diabetes insipidus. Whole-exome sequencing (WES) revealed a novel compound heterozygous mutation of the AIRE gene -the c.239 T > G (p.Val80Gly) variant on one allele and the copy number variant (CNV) of 21q22.3(chr21:45,670,150-45,706,528)*1 on the other. CONCLUSIONS: This case suggests that diabetes insipidus is a rare component of APS-1 and expands the variety of mutations on AIRE gene.

20.
J Ethnopharmacol ; 281: 114458, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34352329

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Qihuzha granule (QHZG), is one of traditional Chinese patent medicines composed of eleven edible medicinal plant, which has been used in the clinic for the treatment of indigestion and anorexia in children caused by deficiency of the spleen and stomach. Yet it is noteworthy that QHZG has therapeutic effect on recurrent respiratory tract infection (RRTI) in children. However, its potential molecular mechanisms remained unclear. AIM OF THE STUDY: The aim of this study was to investigate the therapeutic effect and potential mechanism of QHZG on lipopolysaccharide (LPS) induced acute spleen injury. MATERIALS AND METHODS: The acute spleen injury model was induced by intraperitoneal injection of LPS (10 mg/kg) and safe doses of QHZG was administered by gavage once a day for 23 days before LPS treatment. Serum inflammatory cytokines including interleukin-2 (IL-2), IL-1ß, IFN-γ, and tumor necrosis factor-α (TNF-α) were tested by ELISA. Related protein levels were detected by Western blotting. Hematoxylin-eosin (HE) staining was employed to observe the histological alterations. The distribution of macrophages and neutrophils in the mouse spleen was examined by immunofluorescence analysis. RESULTS: QHZG pretreatment significantly abolished the increased secretion of cytokines such as interleukin-2 (IL-2), IL-1ß, IFN-γ, and tumor necrosis factor-α (TNF-α), which were attributable to LPS treatment. Immunofluorescence staining and Histological analysis of spleen tissue revealed the protective effect of QHZG against LPS-induced acute spleen injury in mice. Further study indicated that pretreatment with QHZG significantly inhibited LPS-induced phosphorylation of Src. Accordingly, the increased phosphorylation of Src downstream components (JNK, ERK, P38 and STAT3) induced by LPS was remarkably diminished by QHZG, suggesting the involvement of Src/MAPK/STAT3 pathway in the inhibitory effects of QHZG on spleen injury in mice. CONCLUSION: Our study demonstrated that QHZG protected mice from LPS-induced acute spleen injury via inhibition of Src/MAPK/Stat3 signal pathway. These results suggested that QHZG might serve as a new drug for the treatment of LPS-stimulated spleen injury.

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