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1.
Complement Ther Clin Pract ; 39: 101115, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32379654

RESUMO

BACKGROUND AND PURPOSE: Cervical vertigo (CV), one of the most common causes of vertigo, makes patients feel dizzy, which seriously affects patients' lives. As a traditional Chinese bone-setting manipulation, Tuina is widely used to treat CV. This article aims to evaluate the effectiveness and safety of Tuina for CV. METHODS: Nine databases were searched. Methodological quality was evaluated with the Cochrane Collaboration's tool. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was applied to determine confidence in the effect estimates. Stata 12.0 software was used to carry out the meta-analysis, and a trial sequential analysis (TSA) was performed with TSA 0.9. RESULTS: Nine randomized controlled trials (RCTs) were included. Low-quality evidence suggested that Tuina showed a significantly higher effectiveness rate compared to massage therapy (risk ratio (RR) = 1.11, 95% confidence intervals (CI): 1.05 to 1.17, p < 0.0001) and cervical traction (RR = 1.37, 95% CI: 1.09 to 1.72, p = 0.007; I2 = 0%, p = 0.826). Two trials reported that Tuina was better than acupuncture (RR = 1.40, 95% CI: 1.07 to 1.83) or betahistine mesilate (RR = 1.17, 95% CI: 0.99 to 1.37) based on an improved effectiveness rate. Low-quality evidence showed that Tuina was superior to massage therapy in improving scores on the evaluation scale for cervical vertigo (ESCV) (weighted mean differences (WMD) = 2.52, 95% CI: 1.11 to 3.94, p < 0.0001). Adverse events were tolerable. TSA revealed that an improved effectiveness rate was indicated. CONCLUSION: Tuina might improve the effectiveness rate and ESCV scores in patients with CV. However, the level of all the available evidence was low, and larger-scale and well-designed RCTs should be encouraged.

2.
Allergy Asthma Proc ; 41(3): 218-223, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32375967

RESUMO

The increasing availability of genetic testing for modern immunologists in the evaluation of immune diseases could provide a definite diagnosis in elusive cases. A 27-year-old white male patient presented to the clinic with recurrent sinopulmonary and cutaneous infections since childhood. The patient's mother had seronegative polyarthritis, and one of two sisters of the patient had chronic sinopulmonary infections. Serum immunoglobulins, immunoglobulin G (IgG) subclasses, lymphocyte subset markers, mannose-binding lectin, mitogen and antigen stimulation, bacteriophage study, and Streptococcus pneumoniae titers to 23 serotypes were all normal. B-cell phenotyping revealed a decrease in both nonswitched memory B cells (CD19+CD27+IgD+) and switched memory B-cells (CD19+CD27+IgD-). Genetic testing and the improvement of clinical symptoms after IgG replacement led to the final diagnosis.

3.
J Am Osteopath Assoc ; 120(5): 351-358, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32337569

RESUMO

Historically, osteopathic principles have focused on the appropriate drainage of cranial structures to relieve symptoms of rhinitis, which include nasal congestion, anterior/posterior rhinorrhea, sneezing, and itching. Allergic rhinitis is primarily an aberrant immunologic reaction caused by cytokines secreted from lymphocytes that traverse the lymphatic pathway throughout the body. Several studies have documented that, when manipulated, the lymphatic system enhanced the motion of these lymphocytes to important immune structures in both human and animal models. Additionally, modulation of both sympathetic and parasympathetic outflow has been found either to inhibit or enhance secretion and/or drainage of important allergic sites. Osteopathic approaches to rhinitis play an effective role in the comprehensive management of rhinitis, and techniques based on these approaches are therapeutic options for rhinitis. This article provides an up-to-date literature review about the management of rhinitis using the 5 models of osteopathic medicine: biomechanical, respiratory-circulatory, metabolic, neurologic, and behavioral.

4.
Immunopharmacol Immunotoxicol ; 42(3): 187-198, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32223464

RESUMO

Natural killer (NK) cells play an important role in anti-tumor and anti-infection, and perform their immune surveillance function in various ways. However, no matter what kind of cancer, the functional activity of NK cells in the tumor microenvironment (TME) is suppressed. Understanding the relationship between tumor cells and NK cells is very critical for tumor immunotherapy. This review discusses the mechanism of tumor cells escaping the immune surveillance of NK cells. These include a variety of factors that inhibit the activity of NK cells, an imbalance of activating receptors and inhibiting receptors on NK cells, abnormal binding of receptors and ligands, cross-talk of surrounding cell groups and NK cells in the TME, and other factors that affect NK cell activity. An understanding of these factors is necessary to provide new treatment strategies for tumor immunotherapy.

5.
J Dig Dis ; 2020 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-32336033

RESUMO

AIMS: The diagnostic performance of liver stiffness measurement (LSM) is important to evaluate fibrosis stages in non-alcoholic fatty liver disease (NAFLD) patients. However, whether LSM differs between non-obese vs. obese NAFLD is unknown. METHODS: Patients diagnosed as NAFLD by liver biopsy according to NASH CRN scoring system were consequentially enrolled in this study. Non-obese was defined as BMI less than 25 kg/m2 . LSM measurement was performed by experienced physicians within 2 weeks of liver biopsy. RESULTS: A total of 158 patients were included. The average BMI of non-obese (n = 68) and obese (n = 90) patients was 23.2 ± 1.6 kg/m2 and 27.9 ± 2.5 kg/m2 , respectively. After adjusting age, fibrosis stage, steatosis grade and diabetes, non-obese patients had generally 3.5 kPa lower LSM than obese patients (P = 0.003). LSM values of non-obese patients were evidently lower stratified by fibrosis stage, especially in cirrhosis patients (F4, P = 0.021). Applying separated cut-off for non-obese vs obese NAFLD in individual fibrosis stage, 5.8 vs.7.5 kPa (F1), 7.6 vs. 8.5 kPa (F2), 9.1 vs. 11.2 kPa (F3), and 12.5 vs. 14.3 kPa (F4), diagnostic odds ratios (DORs) were improved than using overall cut-off values. In non-obese NAFLD, using separated cut-off could avoid 9% cirrhosis patients being underestimated. CONCLUSIONS: Non-obese NAFLD patients had lower LSM values than obese patients. Different cut-offs should be used in non-obese and obese NAFLD patients. This article is protected by copyright. All rights reserved.

6.
Sci Rep ; 10(1): 4325, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152407

RESUMO

Aerosol inhalation is a promising strategy for the delivery of antibiotic agents. The efficacy of antibiotic treatment by aerosol inhalation is reduced by the formation of microbial biofilms in the respiratory system and excessive airway mucus build-up. Various approaches have been taken in order to overcome this barrier. In this in vitro study, we used hypertonic saline (7%, by weight), a low cost Food and Drug Administration-approved reagent, as an aerosol carrier to study its effects with the antibiotic, gentamicin, on the most common respiratory opportunistic pathogen, Pseudomonas aeruginosa, present in the mucus. The results indicated that the hypertonic saline aerosol containing gentamicin, a low cost antibiotic, significantly eliminated biofilm growth by ~3-fold, compared to the regular saline aerosol containing gentamicin. In addition to enhancing the penetration efficiency of drug molecules by 70%, bacterial motility also decreased (~50%) after treatment with aerosolised hypertonic saline. In conclusion, our results demonstrate that hypertonic saline can significantly enhance the efficacy of antibiotic aerosols, which may contribute to the current use of inhaled therapeutic compounds.

7.
Acta Pharmacol Sin ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32203083

RESUMO

Alteration in reproductive hormones profile is associated with the increasing risk of menopausal depression in women. Serum follicle-stimulating hormone (FSH) level is changed during the menopause transition, while the effect of FSH on menopausal depression has remained undefined. In this study we investigated whether or how FSH affected menopausal depression in postmenopausal (ovariectomized) FSHR knockout mice (Fshr-/-). We found that Fshr-/- mice displayed aggravated depression-like behaviors, accompanied by severe oxidative stress in the whole brain, resulted from significantly reduced glutamate cysteine ligase modifier subunit (GCLm) in glutathione synthesis and glucose-6-phosphate dehydrogenase (G6PD) in NADP/NADPH transition. Importantly, administration of ROS scavenger N-acetyl cysteine (NAC, 150 mg · kg-1 · d-1, i.p. for 12 weeks) attenuated the depression-like behaviors of Fshr-/- mice. Consistent with these in vivo experiment results, we found that pretreatment with FSH (50, 100 ng/mL) dose-dependently increased protein levels of GCLm and G6PD, and decreased the ROS production in N2a mouse neuroblastoma cells. These findings demonstrate that FSH signaling is involved in pathogenesis of menopausal depression, and likely to maintain the redox-optimized ROS balance in neurons.

8.
Biochem Biophys Res Commun ; 525(4): 915-920, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32171529

RESUMO

Affective disorders are a set of mental disorders and particularly disrupt the mental health of susceptible women during puberty, pregnancy, parturition and menopause transition, which are characterized by dramatic changes in reproductive hormone profiles. The serum FSH level changes significantly during these periods; yet, the role of FSH in mood regulation is poorly understood. In the current study, FSHR knockout (Fshr-/-) mice displayed enhanced affective disorder behaviors in an open field test and a forced swim test, accompanied by altered gene expression profiles. The differentially expressed genes between Fshr-/- mice and Fshr+/+ mice were enriched in multiple neuroendocrine metabolic pathways. FSHR deletion significantly increased/decreased the mRNA and/or protein expression levels of AOX1, RDH12, HTR3a and HTR4 in mood-mediating brain regions, including the hippocampus and prefrontal cortex. These results reveal that FSH signaling is involved in the development of affective disorders.

9.
Eur J Pharmacol ; 876: 173056, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32147436

RESUMO

Hepatic ischemia/reperfusion (I/R) injury is a common complication in the clinical setting. Our previous study has shown that connexin 32 (Cx32) plays a major role in renal I/R injury; however, the role of Cx32 in hepatic I/R injury remains unknown. Liver tissue and serum samples from patients undergoing orthotopic liver transplantation (OLT) were used to evaluate the function of Cx32 in OLT post-reperfusion injury. Then, partial hepatic ischemia was established in global Cx32 knockout mice and wild-type mice followed by reperfusion. Hepatic injury markers were examined. Cx32 small interfering RNA and the p53 inhibitor, pifithrin-α, tenovin-1 were used to examine the relationship between Cx32 and the p53/puma pathways in the BRL-3A and murine primary hepatocytes hypoxia/reoxygenation (H/R) model. Corresponding to liver damage, Cx32 was significantly induced both during OLT in human patients and partial hepatic I/R in mice. Cx32 KO mice exhibited less liver injury than controls. Cx32 deficiency significantly suppressed the p53/puma pathways and hepatocyte apoptosis. Similar results were observed in the BRL-3A and murine primary hepatocytes H/R model. Propofol protected against OLT post-reperfusion injury and hepatocyte apoptosis by inhibiting Cx32. In conclusion Cx32 is a novel regulator of hepatic I/R injury through the modulation of hepatocyte apoptosis and damage, largely via the p53/puma signaling pathway.

10.
Life Sci ; 253: 117539, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32165213

RESUMO

AIMS: Lipopolysaccharide (LPS)-induced intestinal injury is a common clinical feature of sepsis. Aggravated inflammation and higher sensitivity to infection are associated with high-fat diet (HFD) in patients with type 2 diabetes and/or obesity. However, the mechanism by which HFD exacerbates LPS-induced intestinal injury has not been elucidated. This study aims to examine the effects of HFD on intestinal injury induced by LPS and the underlying mechanism. MAIN METHODS: Mice were fed with HFD or regular chow for 12weeks and were then challenged with LPS. Vas2870 was administered to mice that received HFD before the initiation of the diet. The levels of tight junction protein expression, oxidative stress, organ injury, and nicotinamide adenine dinucleotide phosphate (NADPH)-associated proteins were assessed periodically. KEY FINDINGS: LPS treatment resulted in severe intestinal pathological injury and increased oxidative stress, evidenced by significantly increased serum diamine oxidase, reactive oxygen species, malondialdehyde, and intestinal fatty acid binding protein contents. Additionally, a decrease in tight junction protein expression was observed, indicating a loss of tight junction integrity. LPS treatment induced the expression of Nox2 and Nox4. All the effects were more severe in HFD mice. Treatment with vas2870 conferred protection against LPS-induced intestinal injury in HFD-fed mice, partially reduced oxidative stress, and rescued the expression of tight junction proteins. CONCLUSION: HFD aggravated LPS-induced intestine injury through exacerbating intestinal Nox-related oxidative stress, which led to a loss of the integrity of tight junctions and consequently increased intestinal permeability.

11.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1865(6): 158660, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32058034

RESUMO

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secretory protein that promotes low-density lipoprotein receptor (LDLR) degradation and thereby regulating plasma levels of LDL cholesterol. Previous studies have revealed the role of the C-terminal domain (CTD) of PCSK9 in its secretion, however, how CTD regulates PCSK9 secretion is not completely understood. Additionally, SEC24A, the cargo adaptor protein of the coat protein complex II, has been implicated in the secretion of mouse PCSK9. Here, we investigated how CTD and SEC24 regulated PCSK9 secretion in humans. We found that mutant PCSK91-528, in which amino acids from 529 to the end (amino acid 692) were deleted, was maturated and secreted from cells as effectively as the wild-type protein. On the other hand, lacking amino acids 454 to 692 in mutant PCSK91-453 significantly reduced its maturation and secretion, but to a lesser extent when compared to mutants PCSK91-446, PCSK91-445 and PCSK91-444, that all markedly impaired PCSK9 maturation. However, mutant PCSK91-444 virtually eliminated PCSK9 secretion while PCSK91-446 and PCSK91-445 could still be adequately detected in culture medium. Interestingly, mutation of Pro445 to other amino acid residues considerably impaired the secretion of mutant PCSK91-445 but not the full-length protein. We also found that natural variants in CTD including S462P, S465L, E482G, R495Q and A522T impaired PCSK9 secretion. Further, the knockdown of SEC24A, SEC24B, SEC24C but not SEC24D reduced secretion of the full-length PCSK9 but not mutant PCSK91-446. Therefore, SEC24A, SEC24B, and SEC24C facilitate endogenous PCSK9 secretion from cultured human hepatocytes, that are most likely mediated by the CTD of PCSK9. Our studies also indicate that the CTD of PCSK9 may allosterically and independently modulate the stability of the hinge region. Collectively, these data revealed that the CTD of PCSK9 and the hinge region play a critical role in PCSK9 maturation and secretion.

12.
Biomed Environ Sci ; 33(1): 37-47, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-32029057

RESUMO

Objective: To evaluate the effects of incretin-based therapies on body weight as the primary outcome, as well as on body mass index (BMI) and waist circumference (WC) as secondary outcomes. Methods: Databases including Medline, Embase, the Cochrane Library, and clinicaltrials.gov (www.clinicaltrials.gov) were searched for randomized controlled trials (RCTs). Standard pairwise meta-analysis and network meta-analysis (NMA) were both carried out. The risk of bias (ROB) tool recommended by the Cochrane handbook was used to assess the quality of studies. Subgroup analysis, sensitivity analysis, meta-regression, and quality evaluation based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) were also performed. Results: A total of 292 trials were included in this study. Compared with placebo, dipeptidyl-peptidase IV inhibitors (DPP-4Is) increased weight slightly by 0.31 kg [95% confidence interval ( CI): 0.05, 0.58] and had negligible effects on BMI and WC. Compared with placebo, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) lowered weight, BMI, and WC by -1.34 kg (95% CI: -1.60, -1.09), -1.10 kg/m 2 (95% CI: -1.42, -0.78), and -1.28 cm (95% CI: -1.69, -0.86), respectively. Conclusion: GLP-1 RAs were more effective than DPP-4Is in lowering the three indicators. Overall, the effects of GLP-1 RAs on weight, BMI, and WC were favorable.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32086192

RESUMO

OBJECTIVE: We applied low-intensity focused ultrasound (LIFU) stimulation of the ventrolateral periaqueductal gray (vlPAG) in spontaneously hypertensive rats (SHRs) model to demonstrate the feasibility of LIFU stimulation to decrease blood pressure (BP). METHODS: The rats were treated with LIFU stimulation for 20 min every day for one week. The change of BP and heart rate (HR) were recorded to evaluate the antihypertensive effect. Then the plasma levels of epinephrine (EPI), norepinephrine (NE), and angiotensin II (ANGII) were measured to evaluate the activity of the sympathetic nervous system (SNS) and the renin-angiotensin system (RAS). The c-fos immunofluorescence assay was performed to investigate the antihypertensive nerve pathway. Moreover, the biological safety of ultrasound sonication was examined. RESULTS: The LIFU stimulation induced a significant reduction of BP in 8 SHRs. The mean systolic blood pressure (SBP) was reduced from 170 ± 4 mmHg to 128 + 4.5 mmHg after a one-week treatment, p<0.01. The activity of SNS and RAS were also inhibited. The results of the c-fos immunofluorescence assay showed that US stimulation of the vlPAG significantly enhanced the neuronal activity both in vlPAG and caudal ventrolateral medulla (CVLM) regions. And the US stimulation used in this study did not cause significant tissue damage, hemorrhage and cell apoptosis in the sonication region. CONCLUSION: The results support that LIFU stimulation of the vlPAG could relieve hypertension in SHRs. SIGNIFICANCE: The LIFU stimulation of the vlPAG could potentially be a new alternative non-invasive device therapy for hypertension.

14.
Cell Mol Life Sci ; 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32008086

RESUMO

BACKGROUND: Small bowel vascular malformation disease (SBVM) is the most common cause of obscure gastrointestinal bleeding (OGIB). Several studies suggested that EGFL6 was able to promote the growth of tumor endothelial cells by forming tumor vessels. To date, it remains unclear how EGFL6 promotes pathological angiogenesis in SBVM and whether EGFL6 is a target of thalidomide. METHODS: We took advantage of SBVM plasma and tissue samples and compared the expression of EGFL6 between SBVM patients and healthy people via ELISA and Immunohistochemistry. We elucidated the underlying function of EGFL6 in SBVM in vitro and by generating a zebrafish model that overexpresses EGFL6, The cycloheximide (CHX)-chase experiment and CoIP assays were conducted to demonstrate that thalidomide can promote the degradation of EGFL6 by targeting CRBN. RESULTS: The analysis of SBVM plasma and tissue samples revealed that EGFL6 was overexpressed in the patients compared to healthy people. Using in vitro and in vivo assays, we demonstrated that an EMT pathway triggered by the EGFL6/PAX6 axis is involved in the pathogenesis of SBVM. Furthermore, through in vitro and in vivo assays, we elucidated that thalidomide can function as anti-angiogenesis medicine through the regulation of EGFL6 in a proteasome-dependent manner. Finally, we found that CRBN can mediate the effect of thalidomide on EGFL6 expression and that the CRBN protein interacts with EGFL6 via a Lon N-terminal peptide. CONCLUSION: Our findings revealed a key role for EGFL6 in SBVM pathogenesis and provided a mechanism explaining why thalidomide can cure small bowel bleeding resulting from SBVM.

15.
Ultrason Sonochem ; 63: 104935, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31945558

RESUMO

Previous studies have indicated that the presence of microbubbles (MBs) during sonication has an impact on neuronal activity, while the underlying mechanisms remain to be revealed. In this study, a model for the scattered pressures produced by the pulsating lipid-encapsulated MBs in mouse brain was developed to numerically investigate the effect of MBs on neuronal activity during transcranial focused ultrasound stimulation. The additional summed scattered pressure (Psummed_scat) from the oscillating MBs was calculated from the model. The level of neuronal activity was experimentally verified using an immunofluorescence assay with antibodies against c-fos. The pressure difference (ΔP) between acoustic pressures at which the same level of neuronal activity is excited by ultrasound stimulation with and without MBs was obtained from the experiments. The results showed that Psummed_scat accounts for about half of the ΔP when the MBs experience a "compression-only" response. The Psummed_scat suddenly increased at a critical acoustic pressure, around which a rapid enhancement of ΔP obtained from experiment also occurred. This work suggested that the additional scattered pressures from pulsating MBs are probably a mechanism that affects neuronal activity under transcranial focused ultrasound stimulation.

16.
Diabetes Res Clin Pract ; 159: 107999, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31904443

RESUMO

OBJECTIVE: To study the changes in glucose and lipid metabolism indexes and the condition of early atherosclerosis in patients with diabetes with and without obstructive sleep apnea syndrome (OSAS). METHODS: Patients with type 2 diabetes mellitus (DM) aged 32-50 years who did not have significant complications were included. A total of 42 patients with DM with OSAS and 46 patients with DM without OSAS were chosen according to their sleep monitoring indexes. Height and weight were measured, and fasting blood glucose, postprandial blood glucose, endothelin (ET), nitric oxide (NO) and lipid profile were tested. Then, all the subjects were subjected to the pulse wave velocity (PWV) test. RESULTS: The levels of glycated haemoglobin and triglycerides were significantly higher in patients with DM with OSAS than those in patients with DM without OSAS. ET, NO and PWV changed significantly. CONCLUSION: Patients with diabetes with OSAS are more likely to have complications related to arteriosclerosis and aggravation of glycolipid metabolism disorder. Early intervention is recommended.

17.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(1): 116-123, 2020 Jan 15.
Artigo em Chinês | MEDLINE | ID: mdl-31939246

RESUMO

Objective: To explore a new strategy for constructing three-dimensional dermoid tissue in vitro by using cell sheets technology. Methods: Rabbit bone marrow mesenchymal stem cells (rBMSCs) were isolated from bone marrow of New Zealand white rabbits and cultured by whole bone marrow adherent method. Human dermal fibroblasts (HDFs) were cultured and passaged in vitro. The 2nd generation rBMSCs and the 3rd generation HDFs were cultured in a culture dish for 2 weeks with cell sheets conditioned medium respectively to obtain a monolayer cell sheets. Human umbilical vein endothelial cells (HUVECs) were inoculated on rBMSCs sheet to construct pre-vascularized cell sheet. During the culture period, the morphological changes of the cell sheet were observed under an inverted phase contrast microscope. At 1, 3, 7, and 14 days, HE staining and CD31 immunofluorescence staining were performed to observe the cell distribution and microvascular network formation. The rBMSCs sheet was used as control. The pre-vascularized cell sheet (experimental group) and rBMSCs sheet (control group) cultured for 7 days were placed in the middle of two HDFs sheets, respectively, to prepare three-dimensional dermoid tissues. After 24 hours of culture, CD31 immunofluorescence staining and collagen type Ⅰ and collagen type Ⅲ immunohistochemical stainings were performed to evaluate cell distribution and collagen expression. Results: HDFs and rBMSCs sheets were successfully prepared after 2 weeks of cell culture. After inoculation of HUVECs on rBMSCs sheet for 3 days, HUVECs could be seen to rearrange on rBMSCs sheet and forming vacuoles. The reticular structure was visible at 7 days and more obvious at 14 days. The formation of vacuoles between the cell sheets was observed by HE staining, and the vacuoles became more and more obvious, the thickness of the membranes increased significantly with time. CD31 immunofluorescence staining showed the microvascular lumen formation. However, only the thickness of rBMSCs sheet increasing was observed, with no changes in cell morphology or cavitation structure. The three-dimensional dermoid tissue observation showed that the endothelial cells in the experimental group were positive expressions, and the rBMSCs, HDFs, and HUVECs cells were arranged neatly. The endothelial cells were negative expressions and randomly arranged in the control group. The collagen type Ⅰ and collagen type Ⅲ were positive expression in the experimental group and the control group. But compared with control group, experimental group presented a "honeycomb" network connection, where the matrix was distributed regularly, and cells were arranged tightly. The difference in the expression of collagen type Ⅰ and collagen type Ⅲ between the experimental group and the control group was not significant ( P>0.05). Conclusion: Three-dimensional dermoid tissue is successfully constructed by using cell sheet technology. The cell matrix distribution of the pre-vascularized cell sheet constructed by HUVECs and rBMSCs sheet is relatively regular, which has the potential to form tissue engineered dermis.


Assuntos
Cisto Dermoide , Células-Tronco Mesenquimais , Animais , Células da Medula Óssea , Técnicas de Cultura de Células , Diferenciação Celular , Células Cultivadas , Humanos , Coelhos , Engenharia Tecidual
18.
Clin Chim Acta ; 503: 61-69, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31945341

RESUMO

Pregnancy associated atypical hemolytic uremic syndrome (p-aHUS) is a disease with a triad of hemolytic anemia, thrombocytopenia and acute renal failure, which might be attributed to the uncontrolled complement activation. Herein, we sequenced a postpartum-aHUS patient and found the two missense variants of CD46, a novel mutation (c.403G > C, p.G135R) from her father and a once reported mutation (c.293C > T, p.T98I) without expressional and functional tests from her mother. The G135R mutation caused a significantly reduced membrane expression of CD46 in peripheral blood lymphocyte and renal cells. The T98I mutation caused a mild decrease membrane expression of CD46 in peripheral blood lymphocyte cells. Moreover, the expressed G135R protein was in precursor form, indicating that this mutant was retained intracellularly. The C3b binding ability of T98I mutant was slightly decreased while the C4b binding ability is not significantly changed. The cofactor ability of the two mutants for factor I in the degradation of C3b was demonstrated to be impaired. This study reported the first case of a four-generation postpartum-aHUS pedigree with isolated CD46 variants and the detailed disease progression, treatment, and prognosis provided more meaningful information for the understanding the disease.

19.
J Cell Physiol ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31957872

RESUMO

Esophageal squamous cell carcinoma (ESCC) is the predominant esophageal cancer type in China. The aberrant activation of glioma-associated oncogene homolog1 (Gli1), a key factor in Hedgehog (Hh) signaling pathway, has been found in esophageal carcinoma. Moreover, Yes-associated protein 1 (YAP1), the major mediator of Hippo signaling pathway, has been linked to esophageal carcinoma progression. However, the precise roles and the underlying mechanism of both Gli1 and YAP1 in ESCC are unclear. Here, we found that Gli1 and YAP1 are overexpressed in ESCC and are associated with poor prognosis. In addition, we confirmed that knockdown of Gli1 or YAP1 suppresses ESCC cell growth, migration, and invasion in ESCC TE1 and EC109 cells. Significantly, Gli1 interacts with YAP1 in ESCC cells. Both Gli1 and YAP1 proteins are closely correlated with each other in human ESCC samples. Mechanistically, Gli1 upregulates YAP1 in a LATS1-independent manner. Conversely, YAP1 induces Gli1 by regulating phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. Most importantly, we demonstrated that the interaction between Gli1 and YAP1 promotes ESCC tumor growth in vitro and in vivo. Our findings established a novel signaling mechanism by which the interaction between Gli1 and YAP1 promotes ESCC cell growth. This signaling regulation of the tumorigenesis provides a new therapeutic strategy for highly lethal ESCC.

20.
Clin Transl Oncol ; 22(3): 401-410, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31172445

RESUMO

PURPOSE: Hepatitis B core antibody (HBcAb) positivity is regarded as a sensitive marker for occult and prior hepatitis B virus (HBV) infection. However, the prognosis of patients with HBcAb-positive in non-B, non-C hepatocellular carcinoma (NBNC-HCC) remains unclear. The study aimed to compare the clinicopathological characteristics of patients with HBcAb-positive NBNC-HCC to those with overt HBV (hepatitis B surface antigen positive) HCC. METHODS: 306 HCC patients underwent hepatectomy were divided into two groups: an overt HBV-HCC group and HBcAb-positive NBNC-HCC group. Then patients were analyzed using propensity score matching (PSM) to reduce selection bias. Clinicopathological characteristics and survival outcomes were compared between the two groups. Univariate and multivariate analysis for risk factors were also evaluated. RESULTS: HBcAb-positive NBNC-HCC group showed comparable survival outcomes to the overt HBV-HCC group (3-year overall survival rates 66% vs 62%, 69% vs 53%; 3-year recurrence-free survival rates 49% vs 40%, 47% vs 37%; P > 0.05) before and after PSM. Patients with HBcAb-positive NBNC-HCC were older, had more complications, higher proportions of vascular invasion, and larger tumor sizes but lower proportions of cirrhosis, elevated alanine aminotransferase and prothrombin time. CONCLUSIONS: HBcAb-positive NBNC-HCC group had more advanced tumors, but their prognosis was relatively comparable to that of the other group. Therefore, we believe that screening is also necessary in HBcAb-positive patients for early detection of HCC, especially in the elderly.

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