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1.
Med Biol Eng Comput ; 2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-32519006

RESUMO

Coronary arteries have high curvatures, and hence, flow through them causes disturbed flow patterns, resulting in stenosis and atherosclerosis. This in turn decreases the myocardial flow perfusion, causing myocardial ischemia and infarction. Therefore, in order to understand the mechanisms of these phenomena caused by high curvatures and branching of coronary arteries, we have conducted elaborate hemodynamic analysis for both (i) idealized coronary arteries with geometrical parameters representing realistic curvatures and stenosis and (ii) patient-specific coronary arteries with stenoses. Firstly, in idealized coronary arteries with approximated realistic arterial geometry representative of their curvedness and stenosis, we have computed the hemodynamic parameters of pressure drop, wall shear stress (WSS) and wall pressure gradient (WPG), and their association with the geometrical parameters of curvedness and stenosis. Secondly, we have similarly determined the wall shear stress and wall pressure gradient distributions in four patient-specific curved stenotic right coronary arteries (RCAs), which were reconstructed from medical images of patients diagnosed with atherosclerosis and stenosis; our results show high WSS and WPG regions at the stenoses and inner wall of the arterial curves. This paper provides useful insights into the causative mechanisms of the high incidence of atherosclerosis in coronary arteries. It also provides guidelines for how simulation of blood flow in patient's coronary arteries and determination of the hemodynamic parameters of WSS and WPG can provide a medical assessment of the risk of development of atherosclerosis and plaque formation, leading to myocardial ischemia and infarction. The novelty of our paper is in our showing how in actual coronary arteries (based on their CT imaging) curvilinearity and narrowing complications affect the computed WSS and WPG, associated with risk of atherosclerosis. This is very important for cardiologists to be able to properly take care of their patients and provide remedial measures before coronary complications lead to myocardial infarctions and necessitate stenting or coronary bypass surgery. We want to go one step further and provide clinical application of our research work. For that, we are offering to cardiologists worldwide to carry out hemodynamic analysis of the medically imaged coronary arteries of their patients and compute the values of the hemodynamic parameters of WSS and WPG, so as to provide them an assessment of the risk of atherosclerosis for their patients. Graphical abstract Theme and aims: Coronary arteries have high curvatures, and hence flow through them causes disturbed flow patterns, resulting in stenosis and atherosclerosis. This in turn decreases the myocardial flow perfusion, causing myocardial ischemia and infarction. Therefore, in order to understand the mechanisms of these phenomena caused by high curvatures and branching of coronary arteries, we have conducted elaborate hemodynamic analysis for both (i) idealized coronary arteries with geometrical parameters representing curvatures and stenosis, and (ii) patient-specific coronary arteries with stenoses. Methods and results: Firstly, in idealized coronary arteries with approximated realistic arterial geometry representative of their curvedness and stenosis, we have computed the hemodynamic parameters of pressure drop, wall shear stress (WSS) and wall pressure gradient (WPG), and their association with the geometrical parameters of curvedness and stenosis. Then, we have determined the wall shear stress and wall pressure gradient distributions in four patient-specific curved stenotic right coronary arteries (RCAs), that were reconstructed from medical images of patients diagnosed with atherosclerosis and stenosis, as illustrated in Figure 1, in which the locations of the stenoses are highlighted by arrows. Figure 1: Three-dimensional CT visualization of arteries in patients with suspected coronary disease. The arteries can be seen as a combination of various curved segments with stenoses at unspecific locations highlighted by arrows. Our results show high WSS and WPG regions at the stenoses and inner wall of the arterial curves, as depicted in Figure 2. Therein, the encapsulations show (i) high WSS, and (ii) high WPG regions at the stenosis and inner wall of the arterial curves. Figure 2: WSS and WPG surface plot of realistic arteries (a), (b), (c) and (d), wherein the small squared parts are enlarged to show the detailed localized contour plots at the stenotic regions. Therein, the circular encapsulations show (i) high WSS and (ii) high WPG regions at the stenosis and inner wall of the arterial curves. Conclusion and novelty: This paper provides useful insights into the causative mechanisms of the high incidence of atherosclerosis in coronary arteries. It also provides guidelines for how simulation of blood flow in patient coronary arteries and determination of the hemodynamic parameters of WSS and WPG can provide a medical assessment of the risk of development of atherosclerosis and plaque formation, leading to myocardial ischemia and infarction. The novelty of our paper is our showing how in actual coronary arteries (based on their CT imaging), curvilinearity and narrowing complications affect the computed WSS and WPG associated with risk of atherosclerosis. This is very important for cardiologists to be able to properly take care of their patients and provide remedial measures before coronary complications lead to myocardial infarctions and necessitate stenting or coronary bypass surgery.

2.
Virulence ; 11(1): 769-780, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32507026

RESUMO

BACILLUS CEREUS: is an opportunistic pathogen that can cause emetic or diarrheal foodborne illness. Previous studies have identified multiple pathogenic B. cereus strains and characterized a variety of virulence factors. Here, we demonstrate that the virulence and lethality of B. cereus for mammalian cells and host animals involve the interaction of B. cereus flagellin proteins and the host-cell-surface-localized glycosphingolipid Gb3 (CD77, Galα1-4Galß1-4Glcß1-Cer). We initially found that B. cereus infection was less lethal for Gb3-deficiencient A4galt -/- mice than for wild-type mice. Subsequent experiments established that some factor other than secreted toxins must account of the observed differential lethality: Gb3-deficiencient A4galt -/- mice were equally susceptible to secreted-virulence-factor-mediated death as WT mice, and we observed no differences in the bacterial loads of spleens or livers of mice treated with B. cereus strain vs. mice infected with a mutant variant of incapable of producing many secreted toxins. A screen for host-interacting B. cereus cell wall components identified the well-known flagellin protein, and both flagellin knockout strain assays and Gb3 inhibitor studies confirmed that flagellin does interact with Gb3 in a manner that affects B. cereus infection of host cells. Finally, we show that treatment with polyclonal antibody against flagellin can protect mice against B. cereus infection. Thus, beyond demonstrating a previously unappreciated interaction between a bacterial motor protein and a mammalian cell wall glycosphingolipid, our study will provide useful information for the development of therapies to treat infection of B. cereus.

3.
Asian J Androl ; 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541127

RESUMO

This study was performed to summarize our clinical experience with testicular descent and fixation through a scrotal stria incision for the treatment of palpable cryptorchidism in children. This study included 1034 children with palpable cryptorchidism from March 2009 to March 2019. A scrotal stria incision was used to perform testicular descent and fixation. Overall, 1020 children successfully underwent surgical testicular descent and fixation through a scrotal stria incision, and 14 patients underwent conversion to inguinal incision surgery. All patients were discharged 1-2 days after the operation. During hospitalization and follow-up, 55 patients developed complications, including 10 patients with testicular retraction, 7 with poor healing of the incision, and 38 with a scrotal hematoma. No patients developed testicular atrophy, an indirect inguinal hernia, or a hydrocoele. Testicular descent and fixation through a scrotal stria incision for the treatment of palpable cryptorchidism in children is safe and feasible in well-selected cases. This method has the advantages of no scarring and a good cosmetic effect.

4.
Medicine (Baltimore) ; 99(24): e20743, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541527

RESUMO

Micoendoscopic discectomy (MED) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) has become alternatives of the traditional open decompression surgery alone and decompression plus fusion surgery in the treatment of lumbar spinal stenosis (LSS). To date, there is no study focusing on the comparison of clinical outcomes after MED and MIS-TLIF for LSS without spondylolisthesis.Four hundred ninety-seven patients who underwent MED (236 cases) or MIS-TLIF (261 cases) for LSS without spondylolisthesis were included in this study. Perioperative outcomes (hospital stay, operation time and blood loss), cost, functional scores (Oswestry Disability Index, 12-item short form health survey) with a 24-month follow-up visit, complication and reoperation condition within 24 months after surgery were recorded and assessed.No significant difference of clinical outcomes over time was observed between these 2 surgical approaches. Compared with MIS-TLIF, MED was associated with greater satisfaction at 1-month time point postoperatively, whereas this effect was equalized at 3-month time point postoperatively. MED brought advantages in shorter hospital stay, shorter operation time, less blood loss, and less cost over MIS-TLIF.There was no significant difference in 24-month function scores over time between MED group and MIS-TLIF group. Compared with MIS-TLIF, MED could result in a better perioperative effect and less cost.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32427037

RESUMO

Purpose: The purpose of this study was to summarize the clinical experience with laparoscopic percutaneous extraperitoneal closure of the internal ring using an epidural needle for inguinal hernias in girls.Material and methods: A total of 462 girls with inguinal hernias participated in this study from January 2013 to June 2019. Laparoscopic percutaneous extraperitoneal closure of the internal ring via an epidural needle was used to treat these patients.Results: All 462 girls with an inguinal hernia successfully underwent laparoscopic surgery. The operative times for unilateral and bilateral inguinal hernias were 15 (11-25) minutes and 23 (18-33) minutes, respectively. All patients were discharged 1-2 days after the operations. During the hospitalization and follow-up periods, none of the following complications were observed: hernia recurrence, umbilical hernia, abdominal wall vascular injury, intestinal injury or bladder injury. However, there were six patients with complications: two cases of poor healing of the umbilical incision, three cases of suture granulomas and one case of groin traction pain and discomfort.Conclusion: Laparoscopic percutaneous extraperitoneal closure of the internal ring using an epidural needle is a safe and feasible method for the treatment of inguinal hernias in girls. This method has the advantages of limited trauma, no scarring and a good cosmetic effect.

6.
Chem Commun (Camb) ; 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32436508

RESUMO

Herein we first report a dual-responsive peptide substrate (Comp. 1) for preparing self-assembled nanomaterials triggered by pH and legumain. The dual-responsive self-assembly of Comp. 1 in glioma cells enables its long retention time in lysosomes, S phase arrest, and cell growth locking. We verified that the blocked degradation of HIF-1α in lysosomes played a key role in cell cycle arrest and decreased DNA replication. This work illustrates the disturbance of lysosomal function by self-assembled nanomaterials as a promising strategy for inhibiting glioma cell growth.

7.
Injury ; 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32430192

RESUMO

BACKGROUND: Surgical treatment of sacral fractures is difficult, both for reduction and stabilization. Traditional surgical reduction and internal fixation require a long duration of operation leading to extra blood loss, extensive tissue damage, and increased risk of post-operation complications. The purpose of this study was to evaluate the feasibility of a minimally invasive technique that could be more effective, more tissue sparing, and lead to less bleeding. We hypothesized that a Pararectus approach for anterior fixation of unstable sacral fractures would be reliable and more advantageous and significantly improve the outcome of sacral fracture repair. METHODS: Twelve patients with unstable sacral fractures were recruited and examined by CT scanning. A 3D model of each sacral fracture was reconstructed. The computer-assisted 3D image of the reduced pelvis was 3D printed for surgery simulation and plate pre-bending. All cases were treated operatively with the anterior anatomical reduction and internal fixation via a minimally invasive Pararectus approach. VAS, Matta, and Majeed scores were used to evaluate outcomes of the operation. RESULTS: Pre-operations were consistent with the actual surgeries in all cases. The pre-bent plates had an anatomical shape specifically fit to the individual pelvis without further adjustment at the time of surgery, and fracture reductions were significantly improved with little invasive tissue damage. The average operation time was 110 min. The intraoperative blood loss and incision length averaged 695 ml and 6.7 cm, respectively. A high percentage of all cases achieved a diaplasis with an excellent or good score according to the Matta and Majeed standards (83.33% and 91.67%, respectively).All patients achieved clinical healing with an average healing time of 8 weeks. CONCLUSION: 3D printing-assisted anterior fixation of unstable sacral fractures via a minimally invasive Pararectus approach is feasible. This new surgical strategy minimizes trauma damage and bleeding and produces satisfactory reduction and therapeutic efficacy.

8.
Cell Death Dis ; 11(5): 312, 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32366855

RESUMO

Tempol (4-hydroxy-2,2,6,6-Tetramethylpiperidine-1-oxyl, TPL), a nitroxide compound, inhibits proliferation and increases the vulnerability of cancer cells to apoptosis induced by cytotoxic agents. However, the molecular mechanism of TPL inhibiting cancer cell proliferation has not been fully understood. In this study, we evaluated the metabolic effect of TPL on cancer cells and explored its cancer therapeutic potential. Extracellular flow assays showed that TPL inhibited cellular basal and maximal oxygen consumption rates of mitochondrial. 13C metabolic flux analysis showed that TPL treatment had minimal effect on glycolysis. However, we found that TPL inhibits glutamine metabolism by interfering with the oxidative tricarboxylic acid cycle (TCA) process and reductive glutamine process. We found that the inhibitory effect of TPL on metabolism occurs mainly on the step from citrate to α-ketoglutarate or vice versa. We also found that activity of isocitrate dehydrogenase IDH1 and IDH2, the key enzymes in TCA, were inhibited by TPL treatment. In xenograft mouse model, TPL treatment reduced tumor growth by inhibiting cellular proliferation of xenograft tumors. Thus, we provided a mechanism of TPL inhibiting cancer cell proliferation by interfering with glutamine utilization that is important for survival and proliferation of cancer cells. The study may help the development of a therapeutic strategy of TPL combined with other anticancer medicines.

9.
Med Sci Monit ; 26: e921555, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32407297

RESUMO

BACKGROUND This study aimed to investigate the safety and effectiveness of laparoscopic pyloromyotomy for infants with congenital hypertrophic pyloric stenosis. MATERIAL AND METHODS The clinical data of 233 infants with congenital hypertrophic pyloric stenosis who were treated at our hospital from January 2013 to January 2018 were analyzed retrospectively. The patients were divided into 2 groups: the laparoscopic group (group A, n=126) and the conventional operation group (group B, n=107). RESULTS Laparoscopic surgery was successfully performed in all patients in the laparoscopic group, and none of the surgeries were converted to open surgery. Compared with traditional surgery, laparoscopic surgery has obvious advantages in operation time (29.8±12.9 minutes versus 37.2±17.5 minutes, P=0.012), postoperative feeding time (10.3±2.2 hours versus 15.2±4.1 hours, P=0.035), postoperative hospitalization time (2.8±0.7 days versus 3.5±1.9 days, P=0.013), incision length (0.9±0.2 cm versus 3.3±0.8 cm, P=0.002) and poor wound healing (0 versus 6, P=0.007). No complications, such as bleeding, gastric perforation, duodenal injury, abdominal infection or recurrent vomiting, were observed in the 2 groups. The growth and development (weight and height) of the infants in both groups were normal. CONCLUSIONS Laparoscopic pyloromyotomy has the same safety and effectiveness as the traditional operation and has the advantages of less trauma, faster recovery and cosmetically pleasing incisions.

10.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(3): 242-247, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32389172

RESUMO

Objective To investigate the mechanism of formononetin regulating the heat production of brown adipocytes via decoupling protein 1 (UCP1). Methods The brown preadipocytes was isolated from wild-type (WT) C57BL/6J mice and differentiated into mature fat cells in vitro. Moreover, the mRNA levels of fatty acid binding protein 4 (FABP4) and adiponectin were detected by real-time quantitative PCR (RT-qPCR). To confirm formononetin could induce the expression of thermogenic genes, we first prepared WT mature brown adipocytes and treated them with DMSO and formononetin separately. The mRNA and protein levels of thermogenic genes, such as peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), peroxisome proliferators-activated receptor γ (PPARγ), UCP1 and iodothyronine deiodinase 2 (Dio2), were detected by RT-qPCR and Western blot analysis. To investigate the role of UCP1 in mediating differentiation of brown preadipocytes, Fabp4 and adiponectin mRNA levels were analyzed by RT-qPCR in WT and UCP1 mutation differentiated brown adipocytes. To determine cellular oxygen consumption, isolated WT and UCP1 mutation brown preadipocytes were plated in an XF24-well microplate and differentiated into mature brown adipocytes treated with formononetin or DMSO, followed by oxygen consumption rate (OCR) measurement using XF24 analyser. Results Both WT and UCP1 KO brown preadipocytes could be differentiated into adipocyte. The expression of thermogenic genes, including PGC-1α, Dio2, PPARγ and UCP1, induced by formononetin was similar in UCP1 KO adipocytes and WT cells. But the ability of formononetin to increase cellular respiration was inhibited in Ucp1 KO cells. Conclusion Formononetin mediated stimulation of thermogenesis and oxygen consumption via UCP1 in brown fat cells.

11.
J Cardiothorac Surg ; 15(1): 55, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228652

RESUMO

PURPOSE: The purpose of this study was to investigate the effectiveness and safety of the operation for type III esophageal atresia using a thoracoscope. METHODS: The clinical data for 92 patients with type III esophageal atresia in our hospital from January 2015 to December 2018 were analyzed retrospectively. There were 49 patients in group A who underwent thoracoscopic surgery and 43 patients in group B who underwent conventional surgery. RESULTS: The mechanical ventilation time (55.7 ± 11.4 h vs 75.6 ± 19.2 h), intensive care time (3.6 ± 1.8d vs 4.7 ± 2.0d), postoperative hospitalization time (13.1 ± 2.2d vs 16.8 ± 4.3d), thoracic drainage volume (62.7 ± 25.5 ml vs 125.4 ± 46.1 ml), blood transfusion volume (30.5 ± 10.4 ml vs 55.3 ± 22.7 ml) and surgical incision length (2.0 ± 0.5 cm vs 8.0 ± 1.8 cm) in group A were lower than those in group B, and the differences were statistically significant (P < 0.05). Among the postoperative complications, the incidences of postoperative severe pneumonia (8.2% vs 23.3%), poor wound healing (2.0% vs 14.0%) and chest wall deformity (0% vs 11.6%) in group A were significantly lower than those in group B (P < 0.05). There was no significant difference in the incidence of anastomotic stricture, tracheomalacia or gastroesophageal reflux between the two groups after surgery and early during follow-up (P > 0.05), and there were no complications such as achalasia signs and esophageal diverticulum in either group. CONCLUSION: Surgery for type III esophageal atresia via thoracoscopy has the same safety and clinical effectiveness as traditional surgery and has the advantages of smaller incision and chest wall deformity.

12.
J Colloid Interface Sci ; 574: 162-173, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32311538

RESUMO

The integration of multiscale micro- and macroenvironment has been demonstrated as a critical role in designing biomimetic scaffolds for peripheral nerve tissue regeneration. While it remains a remarkable challenge for developing a biomimetic multiscale scaffold for enhancing 3D neuronal maturation and outgrowth. Herein, we present a 3D bioprinted multiscale scaffold based on a modular bioink for integrating the 3D micro- and macroenvironment of native nerve tissue. Gelatin methacryloyl (GelMA)/Chitosan Microspheres (GC-MSs) were prepared by a microfluidic approach, and the effect of these microspheres on enhancing neurite outgrowth and elongation of PC12 cells was demonstrated. The 3D multiscale composite scaffolds were bioprinted based on microspheres and hydrogel as the modular bioink. The co-culture of PC12 cells and RSC96 Schwann cells within these 3D biomimetic scaffolds were investigated to evaluate such a 3D multiscale environment for neurite outgrowth and Schwann cell proliferation. These results indicate that such multiscale composite scaffold with hydrogel microspheres provided a suitable 3D microenvironment for enhancing neurite growth, and the 3D printed hydrogel network provided a 3D macroenvironment mimicking the epineurium layer for Schwann cells proliferation and nerve cell organization, which is promising for the great potential applications in nerve tissue engineering.

13.
Prostate ; 80(8): 640-652, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32282098

RESUMO

BACKGROUND: Androgen receptor (AR) is crucial for prostate cancer (PCa) initiation and malignant progression. Only half of androgen-responsive genes have been identified as having androgen-responsive elements, suggesting that AR regulates downstream genes through other transcriptional factors. However, whether and how AR regulates the progression via regulating these androgen-responsive genes remains unclear. METHODS: Androgen-responsive and activity-changed (AC) transcriptional factors (TFs) were identified based on the time-course gene-expression array and gene promoter regions analysis. The intersection of androgen-responsive and AC TFs was selected the core TFs, which were used to construct the core transcriptional regulatory network. GO enrichment analysis, cell proliferation assays, glycolysis experiments, and reverse transcription polymerase chain reaction analysis were used to analyze and validate the functions of the network. As one of the core TFs, the function and mechanism of IRF1 have been further explored. RESULTS: We devised a new integrated approach to select core TFs and construct core transcriptional regulatory network in PCa. The 24 core TFs and core transcriptional regulatory network participate in regulating PCa cell proliferation, RNA splicing, and cancer metabolism. Further validations showed that AR signaling could promote glycolysis via inducing glycolytic enzymes in PCa cells. IRF1, a novel target of AR, served as a tumor suppressor by inhibiting PCa proliferation, cell cycle, and glycolysis. CONCLUSIONS: It is the first time to demonstrate the regulating role of the AR-mediated transcriptional regulatory network in a series of important biological processes in PCa cells. IRF1, an AR-regulated TF, acts as tumor suppressor in this core transcriptional regulatory network, which highlights the therapeutic potential of targeting this regulatory network for PCa.

14.
Med Biol Eng Comput ; 58(4): 805-814, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32016806

RESUMO

To explore the mechanical mechanism and provide preoperative planning basis for transtrochanteric rotational osteotomy (TRO) procedure, a joint-preserving procedure for osteonecrosis of the femoral head. Eleven TRO finite element femurs with the most common types of necrosis were analyzed under multi-loading conditions. Thereafter, we made a comprehensive evaluation by considering the anatomy characters, daily activities, and risk indicators contain necrosis expansion trend, necrotic blood supply pressure, and the risk of fracture. The risk of fracture (ROF) is the lowest when standing on feet and increases gradually during normal walking and walking upstairs and downstairs. Compared with posterior rotation, rotating forward keeps more elements at low risk. Additionally, the correlation analysis shows it has a strong negative correlation (R2 = 0.834) with the average modulus of the roof. TRO finally decreased the stress and energy effectively. However, the stress and strain energy arise when rotated posteriorly less than 120°. The comprehensive evaluation observed that rotating forward 90°could reduce the total risks to 64%. TRO is an effective technique to prevent collapse. For the anterior and superior large necrosis, we recommend to rotate forward 60° to 90° (more efficient) or backward 180°. The methodology followed in this study could provide accurate and personalize preoperative planning. Graphical Abstract A proximal femur was reconstructed and modified using Mimics from a series of computed tomography. The models were meshed after solidified and performed different osteotomy, and then assigned material based on the Hounsfield Unit from CT images. Finally, 44 different TRO finite element femurs were analyzed under multi-loading conditions and evaluated comprehensively.

15.
Eur J Pharmacol ; 874: 172990, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32057718

RESUMO

Ovarian carcinoma (OC) begins in the ovaries and remains a highly lethal malignancy. Despite great efforts have been made to fight against OC, there still remain limited therapeutic options owing to chemotherapy drug resistance and serious side effects. Osthole is a derivative of coumarin and extracted from Cnidium monnieri (L.) Cusson, which has been drawn more attention due to its high biological activity in various disease. However, the underlying mechanism of osthole in OC is still unclear. In this study, we aim to evaluate the mechanism of osthole against OC cells. Methodologically, Cell Counting Kit-8 (CCK-8) and LIVE/DEAD™ Cell Imaging experiments were employed to assess cell viability. 2',7'-Dichlorofluorescin diacetate (DCFH-DA) staining, flow cytometry, Hoechst staining, JC-1 staining assay and western blotting were performed to study apoptosis. Transmission electron microscopy, western blotting and monodansyl cadaverine (MDC) staining assay were used to study autophagy. Western blotting and microscopy image were employed to determine pyroptosis. Our results demonstrated that osthole could significantly suppress OC cells growth in a dose-dependent manner. We further proved that osthole could inhibit OC cells growth by mitochondria-mediated apoptosis. Meanwhile, we also discovered that osthole could trigger cell autophagy and lead to cell death. Furthermore, our study revealed that osthole could lead to pyroptosis through inducing the cleavage of gasdermin E (c-GSDME) level. Taken together, Osthole could significantly suppress the growth of OC cells and induce OC cells death via apoptosis, pyroptosis and autophagy, which is a promising new drug for the treatment of OC.

16.
J Anat ; 236(5): 916-922, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31961950

RESUMO

Many studies have demonstrated the association between facet tropism and disc herniation in the lumbar spine. Some of them found that lumbar disc herniation was on the side of the more sagittal facet joint interface. However, little is understood about the association of facet tropism with disc herniation in the cervical spine. As the relationship between the facet orientation and the side of cervical disc herniation (CDH) is unclear, the purpose of this study is to investigate that relationship. Ninety-six patients with single-level CDH (C4-C5, C5-C6 or C6-C7) were included in the CDH group of this study. Another 50 age-matched and gender-matched healthy participants who accepted physical examinations were enrolled as the control group. The cervical facet angles of two sides were measured using axial computed tomography (CT). The intersection angle of the midsagittal line of the vertebra to the facet line represents the facet angle. Facet tropism was defined as the angular difference of 7º between the left and the right sides. Facet tropism angle was recorded as the absolute value of the difference of facet angles between two sides. There were 20 herniations at C4-C5 level, 50 herniations at C5-C6 level and 26 herniations at C6-C7 level. The present study showed that more cases in the CDH group had facet tropism than did those in the control group at C4-C5, C5-C6 and C6-C7 level (p = .021, p = .001, p = .015, respectively). The facet tropism angles in the CDH group were significantly bigger than those in the control group at C4-C5, C5-C6 and C6-C7 level (p = .001, p = .002, p = .028, respectively). In the CDH group, the facet angles on the herniated side were found to be significantly bigger than those on the healthy side at C4-C5, C5-C6 and C6-C7 level (p = .000, p = .000, p = .037, respectively). The findings of this present study suggest that facet tropism is associated with the disc herniation in the cervical spine. We also found that cervical disc herniates towards the side of the bigger facet angle with respect to the sagittal plane. There is a need for future studies to verify the biomechanical impact of facet tropism on CDH.

17.
Mar Biotechnol (NY) ; 22(2): 153-166, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31927644

RESUMO

Brown-marbled grouper, Epinephelus fuscoguttatus, is not only an important commercial fish species, but also an important crossbreeding parent in grouper industry. Improvement of growth traits of this species contributes to the development of grouper breeding. Currently, the development of molecular marker associated with growth of brown-marbled grouper is rare. Thus, we performed the first genome-wide association study (GWAS) for five growth traits in 172 brown-marbled groupers with 43,688 SNPs detected by ddRAD-seq. We identified a total of 5 significant and 18 suggestive QTLs located in multiple chromosomes associated with growth traits. In the 20 kb window of the significant SNPs and suggestive SNPs, 5 and 14 potential candidate genes affecting growth were detected, respectively. Five potential candidate genes near the significantly associated SNPs were selected for expression analysis. Among of which, bmp2k, wasf1, and acyp2 involved in bone development, maintenance of mitochondrion structure, and metabolism were differentially expressed. Interestingly, the SNP 23:29601315 located in the intron of bmp2k was significantly associated with body weight, body length, body height, and body thickness and suggestively associated with total length. We verified the locus using another new group including 123 individuals. The results showed that individuals with CC genotype have better growth traits comparing other individuals. Our findings not only contribute to understanding the molecular mechanism of growth regulation, but also promote the advance of marker-assisted selection in brown-marbled grouper.

18.
Mol Cell ; 77(1): 95-107.e5, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31628042

RESUMO

GTP cyclohydrolase I (GTPCH), 6-pyruvoyltetrahydropterin synthase (PTPS), and sepiapterin reductase (SR) are sequentially responsible for de novo synthesis of tetrahydrobiopterin (BH4), a known co-factor for nitric oxide synthase (NOS). The implication of BH4-biosynthesis process in tumorigenesis remains to be investigated. Here, we show that PTPS, which is highly expressed in early-stage colorectal cancer, is phosphorylated at Thr 58 by AMPK under hypoxia; this phosphorylation promotes PTPS binding to LTBP1 and subsequently drives iNOS-mediated LTBP1 S-nitrosylation through proximal-coupling BH4 production within the PTPS/iNOS/LTBP1 complex. In turn, LTBP1 S-nitrosylation results in proteasome-dependent LTBP1 protein degradation, revealing an inverse relationship between PTPS pT58 and LTBP1 stability. Physiologically, the repressive effect of PTPS on LTBP1 leads to impaired transforming growth factor ß (TGF-ß) secretion and thereby maintains tumor cell growth under hypoxia. Our findings illustrate a molecular mechanism underlying the regulation of LTBP1-TGF-ß signaling by the BH4-biosynthesis pathway and highlight the specific requirement of PTPS for tumor growth.


Assuntos
Proliferação de Células/fisiologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Hipóxia/metabolismo , Proteínas de Ligação a TGF-beta Latente/metabolismo , Fósforo-Oxigênio Liases/metabolismo , Animais , Linhagem Celular , Linhagem Celular Tumoral , Células HCT116 , Células HEK293 , Células HT29 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Óxido Nítrico Sintase/metabolismo , Fosforilação/fisiologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Transdução de Sinais/fisiologia , Fator de Crescimento Transformador beta/metabolismo
19.
Oncology ; 98(3): 138-145, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31722331

RESUMO

PURPOSE: RNA polymerase I subunit D (POLR1D) is involved in the synthesis of ribosomal RNA precursors and small RNAs, but its mechanism in the development and progression of colorectal cancer (CRC) remains ambiguous. Thus, this research aimed to investigate POLR1D's expression and significance in human CRC patients and evaluate its association with clinicopathological characteristics. METHODS: Matched fresh-frozen cancerous and non-cancerous tissues were collected from 100 patients diagnosed with CRC. Immunohistochemical, Western blot, and quantitative real-time polymerase chain reaction analyses were adopted to validate the correlation between POLR1D expression and clinicopathological parameters in CRC tissues and adjacent normal tissues (ANTs). RESULTS: POLR1D expression in CRC tissues was significantly higher than in the ANTs. χ2 test and Spearman's correlative analysis showed that a high POLR1D expression is significantly associated with clinical stage, Dukes stage, tumor differentiation, depth of invasion, and metastasis (p < 0.05). It is not correlated with gender, age, and tumor location and size (p > 0.05). Kaplan-Meier survival curves show that the overall survival (OS) time for the low expression group is remarkably longer than for the high expression group (p < 0.0015). Univariate and multivariate analyses indicate that a high POLR1D expression is an independent prognostic factor for poor OS (p = 0.000). CONCLUSION: The findings of this study strongly indicate that POLR1D plays a pivotal role in the occurrence and progression of CRC. It might be an independent adverse prognostic factor for CRC patients and could serve as a potential therapeutic target for clinical diagnosis in CRC and anticancer drug development.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Colorretais/enzimologia , RNA Polimerases Dirigidas por DNA/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Diferenciação Celular , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , RNA Polimerases Dirigidas por DNA/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral , Regulação para Cima
20.
Arch Orthop Trauma Surg ; 140(2): 177-186, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31538234

RESUMO

PURPOSE: To evaluate S1AI-S4AI screw channels with three-dimensional digital technology simulation analysis and to study the feasibility and applicable features of sacral alar-iliac screw fixation in adults. MATERIALS AND METHODS: Forty (20 men and 20 women) normal adult's pelvic CT scan data sets were selected to reconstruct the three-dimensional pelvic model. The ideal S1AI-S4AI screw channels were simulated, followed by precise measurement of their parameters. RESULTS: The results showed that there were no significant differences in the transverse angles, sagittal angles, radiuses of the maximal inscribed circles, or lengths of the screw channels in S1AI-S2AI screws between genders (P > 0.05). In contrast, the radiuses of the maximal inscribed circles on the left and right, respectively, were 5.93 ± 1.02 mm and 5.92 ± 1.04 mm in males and 4.64 ± 0.98 mm and 4.59 ± 0.95 mm in females, and there was a significant difference in S3AI screws between genders (P < 0.05). With a radius of 2.50 mm considered to be standard, there were 25 cases (62.5%) with an S4AI screw channel radius ≤ 2.50 mm in 40 adults, and 15 cases (37.5%; 9 males and 6 females) with a radius > 2.50 mm. Furthermore, the transverse angles, the sagittal angles, the lengths of the screw channels, and the radiuses of the maximal inscribed circles were significantly different between genders in 15 cases (P < 0.05). CONCLUSION: Only one maximum ideal screw can be placed on one side at a time. With a radius of 2.50 mm considered to be standard, it is feasible to place S1AI-S3AI screws with a radius > 2.50 mm in the entire adult population and S4AI screws with a radius > 2.50 mm in some of the adult population. Furthermore, preoperative three-dimensional reconstruction and three-matic research software can effectively simulate the sacral alar-iliac screw channels, and they can provide accurate data for clinical applications.

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