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1.
Prenat Diagn ; 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34480803

RESUMO

OBJECTIVE: Investigate the chromosome status and transfer outcomes of embryos selected using routine "best morphology" IVF practices. METHOD: A prospective multi-center, non-selection cohort study involving patients undertaking IVF treatment. Study entry conditions were blastocyst biopsy, >1 embryo with chromosome analysis and frozen transfer of the best morphology embryo. Primary analyses were ßhCG positive, implantation, ongoing pregnancy and birth rates and pregnancy-stage progression failures. RESULTS: After transfer, embryo chromosome status was assigned and outcomes divided into two primary groups - euploids (n=135) and aneuploids (n=53). Compared to euploid embryo transfers, aneuploid embryos had significantly lower primary outcomes (+ßhCG: 67% vs 30%, P<0.0001; IR: 56% vs 19%, P<0.0001; ongoing week 12: 51% vs 9%,P<0.0001; and livebirths: 50% vs 8%, P<0.0001, respectively). Transfers were further subdivided into smaller groups according to their main chromosomal feature. Stage analysis showed higher failure rates for aneuploids to initiate a pregnancy (P<0.0001), higher subclinical miscarriage rate (P=0.0402) and higher clinical miscarriage rate (P=0.0038). CONCLUSION: Routine morphology-based embryo selection resulted in a high euploid selection rate but a significant number of aneuploid embryos were still inadvertently selected for transfer (28%) with the subsequent high failure rates for pregnancy initiation and progression having implications for appropriate patient management. This article is protected by copyright. All rights reserved.

2.
Mediators Inflamm ; 2021: 5573594, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34531703

RESUMO

Background: Abnormal endometrial repair after injury results in the formation of intrauterine adhesions (IUA) and a thin endometrium, which are key causes for implantation failure and infertility. Stem cell transplantation offers a potential alternative for some cases of severe Asherman's syndrome that cannot be treated with surgery or hormonal therapy. Umbilical cord-derived mesenchymal stem cells (UCMSCs) have been reported to repair the damaged endometrium. However, there is no report on the effects of UCMSCs previously seeded on human acellular amniotic matrix (AAM) on endometrial injury. Methods: Absolute ethanol was injected into rat uteri to damage the endometrium. UCMSCs previously seeded on AAM were surgically transplanted. Using a variety of methods, the treatment response was assessed by endometrial thickness, endometrial biomarker expression, endometrial receptivity, cell proliferation, and inflammatory factors. Results: Endometrial thickness was markedly improved after UCMSC-AAM transplantation. The expression of endometrial biomarkers, namely, vimentin, cytokeratin, and integrin ß3, in treated rats increased compared with untreated rats. In the UCMSC-AAM group, the VEGF expression decreased, whereas that of MMP9 increased compared with the injury group. Moreover, in the AAM group, the MMP9 expression increased. The expression of proinflammatory factors (IL-2, TNFα, and IFN-γ) in the UCMSC-AAM group decreased compared with the untreated group, whereas the expression of anti-inflammatory factors (IL-4, IL-10) increased significantly. Conclusions: UCMSC transplantation using AAM as the carrier can be applied to treat endometrial injury in rats. The successful preparation of lyophilized AAM provides the possibility of secondary infectious disease screening and amniotic matrix quality detection, followed by retrospective analysis. The UCMSC-AAM complex may promote the better application of UCMSCs on the treatment of injured endometrium.

3.
Hum Reprod ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34545401

RESUMO

STUDY QUESTION: What is the relationship between mitochondria of granulosa cells (GCs) and age and ovarian function in the patients under the POSEIDON classification? SUMMARY ANSWER: Our results revealed obvious abnormal mitochondrial-related changes in low prognosis IVF population, where age and the function of ovarian reserve exerted a divergent effect on mitochondrial content and function. WHAT IS KNOWN ALREADY: Mitochondria have an important role in the cross-talk between GCs and oocytes. However, factors affecting mitochondria of GCs and related mechanisms are still poorly understood. STUDY DESIGN, SIZE, DURATION: GCs samples were obtained from 119 infertile women undergoing IVF from September 2020 to February 2021. Six groups were investigated by the POSEIDON stratification: young with normal prognosis (C1), aging with normal prognosis (C2), young and low prognosis group with normal ovarian reserve (NOR) (G1), aging and low prognosis group with NOR (G2), young and low prognosis group with diminished ovarian reserve (DOR) (G3), and aging and low prognosis group with DOR (G4). PARTICIPANTS/MATERIALS, SETTING, METHODS: The morphology of GC mitochondria was observed by transmission electron microscopy. MtDNA copy number and mitochondrial replication-related genes were detected by real-time quantitative PCR (qPCR). Mitochondrial membrane potential (MMP) and cytosolic reactive oxygen species (ROS) were detected by confocal microscopy. Cellular glycolysis and aerobic respiratory capacity were analyzed by Seahorse XFe96 Analyzer, and related gene expression and protein levels were assessed by qPCR and Western blot. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to the normal prognosis groups, mitochondrial morphology was impaired in the low prognosis groups, where the young groups (G1, G3) with low prognosis showed phenotypes undergoing oxidative stress (round, vacuolated, swollen with decreased matrix density) and the aging groups (G2, G4) revealed typical aging characteristics (an irregular shape with heterogeneous matrix density and cord-like cristae). Additionally, the degree of corresponding change and damage was more obvious in patients with DOR (G3, G4) regardless of age. For mitochondrial content, the mtDNA copy number in GCs was significantly negatively correlated with age in the low prognosis groups (ß = -0.373, P = 0.005). Interestingly, the relationship between mtDNA copy number and anti-Mullerian hormone score differed between the two age groups with low prognosis, with a negative correlation in the young groups (ß = -0.639, P = 0.049) and a positive correlation in the aging groups (ß = 0.505, P = 0.039). In addition, significantly reduced mitochondrial activity (MMP, ROS) and cell metabolism (both glycolysis and OXPHOS) were observed in the low prognosis groups, with the most obvious decrease being observed in the DOR population. However, the metabolism of the GCs in normal prognosis aging women (C2) shifted from OXPHOS to anaerobic glycolysis. LIMITATIONS, REASONS FOR CAUTION: Owing to the difficulties involved in primary GC collection and culture, the sample size was limited. WIDER IMPLICATIONS OF THE FINDINGS: Mitochondrial abnormality is closely linked to the low prognostic outcome in IVF patients. Supplementing the functional mitochondrial content or improving mitochondrial function by autologous mitochondrial transfer or mitochondrial-related regulating drugs may help improve the clinical outcomes in patients with a low prognosis, especially for those with DOR. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China (No. 21737001), the Peking University Clinical Medicine + X Youth Project (PKU2020LCXQ011), the Research and Development Program of Peking University People's Hospital (No. RDH2017-03; No. RDX2019-06) and the Application of Clinical Features of Capital Special Subject (Z171100001017130). There were no competing interests. TRIAL REGISTRATION NUMBER: This study was registered with the Chinese Clinical Trial Register (Clinical Trial Number: ChiCTR2100045531).

4.
Artigo em Inglês | MEDLINE | ID: mdl-34067545

RESUMO

This study investigated the association between house cleaning frequency and the risk of miscarriage in a case control sample of Chinese population. We recruited 59 pregnant women with clinical pregnancy loss as cases and 122 women who chose to conduct induced abortion as controls. All participants were aged 20~40 years and completed a questionnaire of lifestyle exposure with a trained nurse. The effect of frequency of cleaning up on risk of miscarriage was estimated using multivariable logistic regressions, adjusting for potential confounders. In the present study, it was shown that house cleaning of less than twice per week was significantly associated with cough during day or night with odds ratio (OR) of 2.97 (95% CI: 1.36~6.75, p = 0.007), and cough during day or night was significantly associated with risk of miscarriage with OR of 2.69 (95% CI: 1.22~6.02, p = 0.014). Thus, house cleaning of less than twice per week was statistically significantly associated with miscarriage with OR of 3.05 (95% CI: 1.51~6.31, p = 0.002). We found that females who have their house cleaned less than twice per week are at elevated risk for miscarriage. Therefore, the home of pregnant woman should be cleaned at least twice per week in order to avoid miscarriage.


Assuntos
Aborto Espontâneo , Aborto Espontâneo/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Tosse , Feminino , Humanos , Gravidez , Fatores de Risco
5.
J Am Chem Soc ; 143(23): 8559-8564, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34097382

RESUMO

The unique merits of aptamers, including specificity, high binding affinity, easy cell internalization, and rapid tissue accumulation abilities, have led aptamer-drug conjugates to evolve into one of the most attractive strategies for targeted drug delivery purposes. Nevertheless, the critical role of linkers in regulating anticancer efficacy of these conjugates, especially those engineered by automated modular synthesis techniques, has been rarely explored. In this work, we utilized Sgc8c aptamer and combretastatin A4 to develop three conjugates with either a phosphodiester bond linker, a disulfide bond linker, or a carbamate linker to study their payload release mechanisms and the influence on anticancer efficacy. These investigations allowed us to identify the unique activation pathway of the phosphodiester bond linker that is activated by both nucleophilic attack of glutathione and degradation caused by phosphodiesterase, which is highly associated with the higher cytotoxicity of the conjugate. Importantly, the understanding of the chemistry of phosphodiester bond linker activation allowed us to further design another XQ-2d-CA4 conjugate that can induce pancreatic cancer cells apoptosis in a more efficient manner.

6.
Zhongguo Zhong Yao Za Zhi ; 46(8): 2045-2050, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33982518

RESUMO

In the past few years, continuous manufacturing(CM) has been put forward by the FDA. Pharmaceutical enterprises are encouraged to promote the implementation of CM, which has become a hot research direction of pharmaceutical technology. In February 2019, the FDA issued a draft guideline for the implementation of CM, which greatly promoted the development of CM and provided reference for continuous manufacturing of traditional Chinese medicine(TCM). The production process of TCM is a complex system. With the innovation of production equipment and the promotion of automation and informatization of TCM production, the exis-ting policies, regulations and traditional production control capacity are difficult to meet the market demand for high-quality TCM pro-ducts. In this paper, we reviewed the new technologies and methods of quality control in accordance with the characteristics of TCM production by referring to modern manufacturing technology, information technology and quality control technology. Based on the "QbD" theory and "PAT" technology, process knowledge system(PKS), an advanced control strategy, was proposed to provide a reference for the implementation of CM in TCM production.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Comércio , Controle de Qualidade , Tecnologia Farmacêutica
7.
Orthop Surg ; 13(3): 1102-1110, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33783125

RESUMO

The objective was to introduce a new endoscopic technique-interspinous plasty for low back pain from Baastrup's disease; based on clinical manifestations, imaging findings and diagnostic test, to discuss a detailed diagnostic procedure for Baastrup's disease; and to explore the mechanism of interspinous plasty in pain relief. To our knowledge, there is no report about the results of endoscopic lumbar technique for Baastrup's disease. This study described the successful full-endoscopic surgical treatment for Baastrup's disease, providing a brand-new therapeutic method for patients. Clinical manifestations, imaging findings, including X-ray, computed tomography (CT) and magnetic resonance imaging, and a "positive" diagnostic test with local anesthetic were used to confirm Baastrup's disease in the three included patients. The interspinous plasty procedure, which aimed to recover a physiological gap between the adjacent spinous processes, was performed by full-endoscopic resection of marginal osteophytes. The removal of local inflamed tissue and reducing inflammation via intraoperative saline irrigation also lead to pain relief. Clinical outcomes included visual analog scale (VAS) for low back pain and the Oswestry Disability Index (ODI). The distance between the adjacent spinous processes was measured from the preoperative and postoperative CT scan. We calculated and recorded the difference between preoperative and postoperative measurements. Technical procedures and advantages of interspinous plasty are introduced. The three patients showed improvement in terms of the postoperative VAS of low back pain (from 8 to 2, from 7 to 1 and from 8 to 2) and ODI (from 68.9% to 33.3%, from 77.8% to 28.9% and from 71.1% to 28.9%, respectively) at the 12-month follow-up. Compared postoperative ODI index, the ODI index increased from 26.7% to 33.3% and from 24.4% to 28.9% in two of the cases at the 12-month follow-up. At 1 week, CT confirmed an obvious reduction in the marginal osteophytes between the adjacent spinous processes. Compared with those on preoperative CT images, the distance between adjacent spinous processes on postoperative CT was enlarged from 1 to 4 mm, and a repeated CT scan 3 months later reconfirmed little recrudescent osteoproliferation. In selected cases, full-endoscopic surgical treatment for chronic mechanical back pain as part of the phenomena of Baastrup's disease may be beneficial. The operations in this study were performed under local anesthesia, with satisfactory early clinical outcomes and a low incidence of complications or adverse events. This may be a feasible therapeutic method or an alternative option for patients who cannot tolerate general anesthesia surgery.

8.
Reprod Sci ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33712995

RESUMO

As the vital organelles for cell energy metabolism, mitochondria are essential for oocyte maturation, fertilization, and embryo development. Abnormalities in quantity, quality, and function of mitochondria are closely related to poor fertility and disorders, such as decreased ovarian reserve (DOR), premature ovarian aging (POA), and ovarian aging, as well as maternal mitochondrial genetic disease caused by mitochondrial DNA (mtDNA) mutations or deletions. Mitochondria have begun to become a therapeutic target for infertility caused by factors such as poor oocyte quality, oocyte aging, and maternal mitochondrial genetic diseases. Mitochondrial replacement therapy (MRT) has attempted to use heterologous or autologous mitochondria to rebuild healthy state of oocyte by increasing the amount of mitochondria (e.g., partial ooplasm transfer, autologous mitochondrial transfer), or to stop the transmission of mtDNA diseases by replacing abnormal maternal mitochondria (e.g., pronuclei transfer, spindle transfer, polar body transfer). Among them, autologous mitochondrial transfer is the most promising therapeutic technology as of today which does not involve using a third party, but its clinical efficacy is controversial due to many factors such as the aging phenomenon of germ line cells, the authenticity of the existence of ovarian stem cells (OSC), and secondary damage caused by invasive surgery to patients with poor ovarian function. Therefore, the research of optimal autologous cell type that can be applied in autologous mitochondrial transfer is an area worthy of further exploration. Besides, the quality of germ cells can also be probably improved by the use of compounds that enhance mitochondrial activity (e.g., coenzyme Q10, resveratrol, melatonin), or by innovative gene editing technologies which have shown capability in reducing the risk of mtDNA diseases (e.g., CRISPR/Cas9, TALENTs). Though the current evidences from animal and clinical trials are not sufficient, and some solutions of technical problems are still needed, we believe this review will guide a new direction in the possible clinical applied mitochondrial-related therapeutic strategies in reproductive medicine.

9.
Eur J Pharm Sci ; 157: 105629, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33176191

RESUMO

Macrophages are sentinels of the immune system, which are often hijacked by tumor cells to assist tumor growth and metastasis. Herein our results showed that low dose salinomycin (SAL) in the range of 10-50 nM could efficiently induce M1 macrophage polarization in a dose- and time- dependent manner in vitro, with 30 nM SAL being optimal to generate M1-type macrophages from RAW246.7 cells. In animal study, intratumorally injected SAL (50 µg/kg) increased proportion of CD86 cells (by 28.9%), and decreased CD206 cells (by 14.2%) in transplant 4T1 tumors, in comparison with PBS group. Thus it resulted in significant regression in tumor growth (20% tumor inhibition) and pulmonary metastasis (reduced the number of metastatic nodes by 58%) in SAL group, whereas lipopolysaccharide (LPS) and paclitaxel (PTX) groups showed comparable number of metastatic lesions and volume of tumor. LPS treatment could as well lead to inflammatory reactions in tumor with SAL group, but resulted in systemic inflammation (elevated levels of IL-1α, IL-1ß and TNF-α in serum), and PTX (10 µg/kg) treatment increased both types of macrophages. For the first time, we employed salinomycin below the dose of direct antitumor activity could effectively prime M1 type macrophage stimulation and regress tumor growth and metastasis.


Assuntos
Neoplasias da Mama , Animais , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Macrófagos , Fenótipo , Piranos
10.
Bioconjug Chem ; 32(1): 182-191, 2021 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-33346657

RESUMO

Development of superparamagnetic iron oxide nanoparticles (SPIONs) based theranostics has suffered due to its self-contradictory requirements on water dispersity and drug loadings. Generally well-dispersed SPIONs have excellent MRI performance but are insensitive to magnetism mediated delivery. Besides, loading hydrophobic drugs also hampers the stability of SPIONs which is critical for their biomedical applications. Considering these aspects, we employed curcumin as a cross-linking agent to facilitate the modular assembly of drug and monodisperse SPIONs (Cur/ALN-ß-CD-SPIONs). Interestingly, the saturation magnetization of Cur/ALN-ß-CD-SPIONs is higher than that of ALN-ß-CD-SPIONs, and the value of r2 indicating the negative contrast ability increases to 389.96 mM-1 s-1. Furthermore, the Cur/ALN-ß-CD-SPIONs are very stable in PBS buffer over 3 weeks. The mice treated with Cur/ALN-ß-CD-SPIONs by tail vein injection displayed a better tumor inhibition effect than that of free curcumin. This study provides a simple method for modular assembly of drug and monodisperse SPIONs, which is crucial to the design of SPIONs with superior T2-imaging performance and drug delivery.


Assuntos
Nanopartículas de Magnetita/química , Animais , Linhagem Celular Tumoral , Meios de Contraste/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Interações Hidrofóbicas e Hidrofílicas , Imageamento por Ressonância Magnética/métodos , Camundongos , Microscopia Eletrônica de Transmissão , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
11.
Tzu Chi Med J ; 32(4): 344-350, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33163379

RESUMO

Objective: Safrole, also called shikimol and Sassafras, is the carcinogenic and phenylpropanoid compound extracted from Sassafras tree and anise, betel, and camphor. Moreover, a high concentration of safrole can be occur in the saliva because of betel nut or areca quid chewing which a common habit observed in Southern and Southeastern Asia. Notably, macrophages are crucial phagocytic cells of the immune system. Nonetheless, to date, no evidence has been reported regarding safrole-induced proinflammatory response and the corresponding mechanism in macrophages. Materials and Methods: In the present study, the cytokines expression, NO generation, protein phosphorylation, and expression were assessed by enzyme-linked immunosorbent assay, Griess reagent, and Western blot assay, respectively. Results: In this study, we determined that safrole induces the generation of nitric oxide and proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1ß, and IL-6 in RAW264.7 macrophages in a concentration-dependent manner. Furthermore, inhibitor of κB (IκB) degradation was caused by safrole in a concentration-dependent manner. In addition, the phosphorylation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) family, including p38 MAPK, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase, was induced by safrole began to increase at 10 µM and attained a plateau at 100 µM. Conclusion: These results indicated that safrole induces the expression of proinflammatory responses in macrophages through the NF-κB/IκB pathway and its upstream factor, MAPK family phosphorylation.

12.
J Gen Intern Med ; 35(12): 3449-3457, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33021715

RESUMO

BACKGROUND: Strict medication guidance and lifestyle interventions to manage blood pressure (BP) in hypertensive patients are typically difficult to follow. OBJECTIVE: To evaluate the 1-year effectiveness of lifestyle and drug intervention in the management of rural hypertensive patients. DESIGN: Randomized community intervention trial. PARTICIPANTS: The control group comprised 967 patients who received standard antihypertensive drug intervention therapy from two communities, whereas the intervention group comprised 1945 patients who received antihypertensive drug and lifestyle intervention therapies from four communities in rural China. MAIN MEASURES: Data on lifestyle behaviors and BP measurements at baseline and 1-year follow-up were collected. A difference-in-difference logistic regression model was used to assess the effect of the intervention. KEY RESULTS: BP control after the 1-year intervention was better than that at baseline in both groups. The within-group change in BP control of 59.3% in the intervention group was much higher than the 25.2% change in the control group (P < 0.001). Along with the duration of the follow-up period, systolic and diastolic BP decreased rapidly in the early stages and then gradually after 6 months in the intervention group (P < 0.001). In the intervention group, drug therapy adherence was increased by 39.5% (from 48.1% at 1 month to 87.6% at 1 year) (P < 0.001), more in women (45.6%) than in men (31.2%; P < 0.001). The net effect of the lifestyle intervention improved the rate of BP control by 56.1% (70.8% for men and 44.7% for women). For all physiological and biochemical factors, such as body mass index, waist circumference, lipid metabolism, and glucose control, improvements were more significant in the behavioral intervention group than those in the control group (all P < 0.001). CONCLUSION: The addition of lifestyle intervention by physicians or nurses helps control BP effectively and lowers BP better than usual care with antihypertensive drug therapy alone.


Assuntos
Hipertensão , Preparações Farmacêuticas , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , China/epidemiologia , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Estilo de Vida , Masculino
13.
Nanomaterials (Basel) ; 10(10)2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33036455

RESUMO

Graphene (Gr)/gold (Au) and graphene-oxide (GO)/Au nanocomposites (NCPs) were synthesized by performing pulsed-laser-induced photolysis (PLIP) on hydrogen peroxide and chloroauric acid (HAuCl4) that coexisted with Gr or GO in an aqueous solution. A 3-month-long aqueous solution stability was observed in the NCPs synthesized without using surfactants and additional processing. The synthesized NCPs were characterized using absorption spectroscopy, transmission electron microscopy, Raman spectroscopy, energy dispersive spectroscopy, and X-ray diffraction to prove the existence of hybrid Gr/Au or GO/Au NCPs. The synthesized NCPs were further evaluated using the photocatalytic reaction of methylene blue (MB), a synthetic dye, under UV radiation, visible light (central wavelength of 470 nm), and full spectrum of solar light. Both Gr/Au and GO/Au NCPs exhibited photocatalytic degradation of MB under solar light illumination with removal efficiencies of 92.1% and 94.5%, respectively.

14.
Cancers (Basel) ; 12(8)2020 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-32726929

RESUMO

Lung cancer is the leading cause of cancer death worldwide and the therapeutic strategies include surgery, chemotherapy and radiation therapy. Non-small cell lung cancers (NSCLCs) account for around 85% of cases of lung cancers. Pemetrexed is an antifolate agent that is currently used as the second line chemotherapy drug in the treatment of advanced NSCLC patients with a response rate of 20-40%. The search for any combination therapy to improve the efficacy of pemetrexed is required. The existence of cancer stem cells (CSCs) is considered as the main reason for drug resistance of cancers. In this study, we first found that pemetrexed-resistant NSCLC cells derived from A549 cells displayed higher CSC activity in comparison to the parental cells. The expression of CSC related proteins, such as BMI1 or CD44, and the epithelial-mesenchymal transition (EMT) signature was elevated in pemetrexed-resistant NSCLC cells. We next discovered that the overexpression of BMI1 in A549 cells caused the pemetrexed resistance and inhibition of BMI1 by a small molecule inhibitor, PTC-209, or transducing of BMI1-specific shRNAs suppressed cell growth and the expression of thymidylate synthase (TS) in pemetrexed-resistant A549 cells. We further identified that BMI1 positively regulated SP1 expression and treatment of mithramycin A, a SP1 inhibitor, inhibited cell proliferation, as well as TS expression, of pemetrexed-resistant A549 cells. Furthermore, overexpression of BMI1 in A549 cells also caused the activation of EMT in and the enhancement of CSC activity. Finally, we demonstrated that pretreatment of PTC-209 in mice bearing pemetrexed-resistant A549 tumors sensitized them to pemetrexed treatment and the expression of Ki-67, BMI1, and SP1 expression in tumor tissues was observed to be reduced. In conclusion, BMI1 expression level mediates pemetrexed sensitivity of NSCLC cells and the inhibition of BMI1 will be an effective strategy in NSCLC patients when pemetrexed resistance has developed.

15.
Microorganisms ; 8(5)2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32369936

RESUMO

Molecular mechanisms of biofilm formation in Candida tropicalis and current methods for biofilm analyses in this fungal pathogen are limited. (2) Methods: Biofilm biomass and crystal violet staining of the wild-type and each gene mutant strain of C. tropicalis were evaluated on silicone under synthetic urine culture conditions. (3) Results: Seven media were tested to compare the effects on biofilm growth with or without silicone. Results showed that biofilm cells of C. tropicalis were unable to form firm biofilms on the bottom of 12-well polystyrene plates. However, on a silicone-based platform, Roswell Park Memorial Institute 1640 (RPMI 1640), yeast nitrogen base (YNB) + 1% glucose, and synthetic urine media were able to induce strong biofilm growth. In particular, replacement of Spider medium with synthetic urine in the adherence step and the developmental stage is necessary to gain remarkably increased biofilms. Interestingly, unlike Candida albicans, the C. tropicalis ROB1 deletion strain but not the other five biofilm-associated mutants did not cause a significant reduction in biofilm formation, suggesting that the biofilm regulatory circuits of the two species are divergent. (4) Conclusions: This system for C. tropicalis biofilm analyses will become a useful tool to unveil the biofilm regulatory network in C. tropicalis.

16.
Zoology (Jena) ; 140: 125768, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32279015

RESUMO

Geckos are exceptional at terrestrial locomotion and can move on diverse terrains and surface orientations. Geckos employ cyclical lateral bending of their flexible trunk and tail to coordinate their limb movements. In this study, using an optical motion capture system, we measured the kinematics of this lateral undulation pattern of geckos (Gekko gecko) at increasing locomotion velocity on horizontal plane, 45° inclined plane and vertical plane, respectively. We observed that geckos increased their stride frequency and stride length to increase the locomotion velocity; the effect of stride frequency on the locomotion velocity was greater than that of stride length. With increasing speed, the lateral undulation pattern changed from standing to travelling. The waveform of the trunk movement appeared as single-peak curves in a standing wave at low speeds and was propagated from head to tail in a travelling wave at high speeds. Analysis of the anatomical characteristics and axial angular kinematics of the two patterns revealed that the lateral undulation pattern results from girdle rotation and axial muscle activity. Thus, the travelling wave is the combined effect of the lateral trunk bending and deflection of the body relative to the motion direction.


Assuntos
Lagartos/fisiologia , Locomoção/fisiologia , Animais , Fenômenos Biomecânicos , Marcha/fisiologia
17.
Molecules ; 25(7)2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32244796

RESUMO

Praeruptorin C (PC) reportedly has beneficial effects in terms of antiinflammation, antihypertension, and antiplatelet aggregation, and it potentially has anticancer activity. However, the effect of PC on human non-small cell lung cancer (NSCLC) is largely unknown. Compared with the effects of praeruptorin A and praeruptorin B, we observed that PC significantly suppressed cell proliferation, colony formation, wound closure, and migration and invasion of NSCLC cells. It induced cell cycle arrest in the G0/G1 phase, downregulated cyclin D1 protein, and upregulated p21 protein. PC also significantly reduced the expression of cathepsin D (CTSD). In addition, the phosphorylation/activation of the ERK1/2 signalling pathway was significantly suppressed in PC-treated NSCLC cells. Cotreatment with PC and U0126 synergistically inhibited CTSD expression, cell migration, and cell invasion, which suggests that the ERK1/2 signalling pathway is involved in the downregulation of CTSD expression and invasion activity of NSCLC cells by PC. These findings are the first to demonstrate the inhibitory effects of PC in NSCLC progression. Therefore, PC may represent a novel strategy for treating NSCLC.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Catepsina D/metabolismo , Cumarínicos/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Neoplasias Pulmonares/metabolismo , Transdução de Sinais/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Catepsina D/genética , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Medicamentos de Ervas Chinesas , Regulação da Expressão Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Metástase Neoplásica
18.
Environ Int ; 139: 105686, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32278886

RESUMO

The female reproductive toxicity of per- and polyfluoroalkyl substances (PFAS) has raised concerns, but knowledge about their human preconception exposure is limited. In this study, 15 emerging PFAS were identified in follicular fluid samples from healthy women by using high-resolution mass spectrometry, and Cl-substituted perfluoroalkyl ether sulfonates (Cl-PFESAs) including 4:2, 5:2, 6:2, and 8:2 Cl-PFESAs, 4:4 C8 perfluoroalkyl ether sulfonate (PFESA), C8 perfluoroalkyl ether carboxylate (PFECA), and C8 polyether PFECA (Po-PFECA) were detected in over 50% of 28 follicular fluid samples. Ten legacy PFAS were also detected, and the geometric mean concentration of PFOS was the highest (4.82 ng/mL), followed by PFOA (4.60 ng/mL), 6:2 Cl-PFESA (1.09 ng/mL), PFHxS (0.515 ng/mL), PFNA (0.498 ng/mL), and C8 PFECA (0.367 ng/mL). The blood-follicle transfer efficiencies for PFCAs decreased with increasing chain length (0.96 for PFHpA, 0.56 for PFTriDA), and the transfer efficiencies of C8 PFECA (0.78) was significantly higher than that of PFOA (0.76). The transfer efficiencies of 4:2 Cl-PFESA (0.73), 6:2 Cl-PFESA (0.75) and 8:2 Cl-PFESA (0.91) were significantly higher than that (0.70) of PFOS (p = 0.028, 0.026 and 0.002, respectively). This study constitutes the first report of the human oocyte exposure to emerging PFAS and their blood-follicle transfer abilities.


Assuntos
Ácidos Alcanossulfônicos , Fluorcarbonetos , Alcanossulfonatos , Éteres , Feminino , Líquido Folicular , Humanos
19.
Odontology ; 108(4): 553-559, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32016787

RESUMO

MIR4435-2HG has been characterized as an oncogenic lncRNA in several types of cancer, while its role in oral squamous cell carcinoma (OSCC, a major subtype of oral cancer) has not been characterized. We explored the functionality of MIR4435-2HG in OSCC and investigated its interactions with TGF-ß1. Blood samples were extracted from OSCC patients (n = 44) and healthy volunteers (n = 38), RT-qPCR, CCK-8, Transwell assays and western blot were performed in this study. The results showed that levels of MIR4435-2HG and TGF-ß1 in plasma were upregulated in OSCC. Across OSCC plasma samples, TGF-ß1 and MIR4435-2HG were significantly and positively correlated. Overexpression of MIR4435-2HG resulted in upregulated TGF-ß1 expression, while exogenous TGF-ß1 treatment had no effect on the expression of MIR4435-2HG. Overexpression of MIR4435-2HG and exogenous TGF-ß1 treatment led to promoted, while TGF-ß inhibitor led to inhibited migration, proliferation and invasion of cancer cells. Moreover, TGF-ß inhibitor led to reduced effects of overexpressing MIR4435-2HG. Therefore, MIR4435-2HG regulates the behaviors of OSCC cells by promoting the expression of TGF-ß1.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , RNA Longo não Codificante , Fator de Crescimento Transformador beta1
20.
Oxid Med Cell Longev ; 2019: 9605980, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827712

RESUMO

Acute lung injury (ALI) is a life-threatening disease that is characterised by the rapid onset of inflammatory responses. Lipopolysaccharide (LPS) is an endotoxin that plays an important role in triggering ALI via pneumonia and sepsis. However, no effective therapeutic strategies are currently available to treat ALI. Nerolidol is an aliphatic sesquiterpene alcohol that is found in the essential oils of many flowers as well as floral plants. It has been shown to exhibit anti-inflammatory, antioxidant, and anticancer properties. Herein, we show that nerolidol pretreatment counteracted the histopathological hallmarks in LPS-induced ALI mice. Indeed, nerolidol pretreatment inhibited LPS-induced alveolar-capillary barrier disruption, lung edema, and lipid peroxidation. Moreover, nerolidol pretreatment prevented the LPS from decreasing the enzymatic activities of superoxide dismutase, catalase, and glutathione peroxidase. Importantly, nerolidol treatment enhanced phosphorylation of AMP-activated protein kinase (AMPK) and expression of nuclear factor erythroid-derived 2-related factor 2 (Nrf-2) and heme oxygenase-1 (HO-1). Taken together, our study reveals the novel protective effects of nerolidol in LPS-induced ALI via the induction of antioxidant responses and activation of the AMPK/Nrf-2/HO-1 signalling pathway.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Lipopolissacarídeos/toxicidade , Pneumonia/prevenção & controle , Sesquiterpenos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Heme Oxigenase (Desciclizante)/genética , Heme Oxigenase (Desciclizante)/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pneumonia/metabolismo , Pneumonia/patologia
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