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1.
Orthop Surg ; 12(1): 321-332, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32077261

RESUMO

OBJECTIVE: To evaluate and present the effectiveness of this innovatively designed, elastic locking intramedullary nail (ELIN) in fixation of clavicle fractures. METHODS: The study included 38 patients from July 2014 to July 2017. All of them received intramedullary fixation treated with ELIN, 22 were males and 16 females. The mean age of the patients was 54 years. There were twenty right-side and 18 left-side clavicular fractures. Radiographs were taken to assess the fracture type: 21 were type A, 16 type B, and one type C. General anesthesia or cervical block was given to all patients. A small incision of 3-5 cm was given only to those who needed mini-open reduction. The administration of ELIN and reduction of the fracture was made sure with a C arm machine. After a follow-up of 8 to 33 months, the clinical outcomes were assessed and evaluated. The constant scores and disabilities of the arm, shoulder and hand questionnaire (DASH) were used to determine the outcomes and functional status of the patients. The study was done accordingly to the guidelines provided by the ethics committee. RESULTS: Mean operation time was 25.63 min. Mean follow-up time was 16.5 months. The rate of closed reduction and open reduction was 84% and 16% respectively. There was no shortening of the clavicle. There was no breakage of the nail, though bending of the nail occurred in one patient. Superficial skin infection occurred in three patients at insertion points or the nail tip which was embedded subcutaneously. Skin erosion with nail exposure occurred in a patient with no significant infection. All the other patients had excellent shoulder function. A mini scar was observed in seven patients all the other patients had no scar. Asymmetry was observed in three patients. The mean Constant score was 98.47 and the mean DASH score was 1.55 at the last follow-up. The implant was removed in all the patients. CONCLUSION: Clavicular fractures treated with ELIN is minimally invasive, which presents a safe and novel surgical technique with less complications and a high success rate, excellent aesthetic and quick recovery after surgery. ELIN restores the micro-dynamic stress at the fracture ends and promotes fracture healing, keeps intact the fracture hematoma and maintains the blood supply, accelerates healing and thus leads to faster osseous healing and better restoration of clavicle length.

2.
Mol Cell Probes ; : 101540, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32084582

RESUMO

AIM: LncRNA MALAT1 is involved in regulation of angiogenesis, however, its expression and mechanism in infantile hemangioma (IH) are less reported. The study aimed to investigate MALAT1 in IH and to reveal the potential mechanism of MALAT1 acting on IH. METHODS: Isolated form IH tissue, human CD31+ hemangioma endothelial cells (HemECs) were cultured and sorted by magnetic-activated cell sorting (MACS). Quantitative real-time (qRT)-PCR was performed to detect the expressions of MALAT1, miR-206 and VEGFA. The correlations among MALAT1, miR-206 and VEGFA were confirmed by bioinformatics analysis and dual-luciferase reporter assay. The effects of MALAT1, miR-206 and VEGFA on cell proliferation were detected by cell counting kit-8 (CCK-8) and cell colony formation assay. Flow cytometry, wound scratch, Transwell and Tube formation assay were performed to determine cell apoptosis, migration, invasion and vasoformation, respectively. Apoptosis-related proteins were determined by Western blot. RESULTS: The results showed that MALAT1 and VEGFA were high-expressed and miR-206 was low-expressed in IH tissues. SiMALAT1 negatively affected the cell proliferation, migration, invasion and vasoformation of HemECs and promoted apoptosis of HemECs. Moreover, Bcl-2 expression was significantly inhibited and the expressions of Bax and c cleaved-3 were greatly promoted. MALAT1 directly targeted and inhibited the expression of miR-206, and VEGFA was predicted to be the target gene for miR-206. SiMALAT1 suppressed the cell proliferation, migration, invasion and vasoformation of HemECs through modulating miR-206/VEGFA axis. CONCLUSION: Knock-down of MALAT1 inhibits the growth of HemECs through regulating miR-206/VEGFA axis, indicating that MALAT1 is a potential therapeutic mechanism for the treatment of IH.

3.
Reprod Sci ; 27(1): 93-99, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32046387

RESUMO

Hepatocellular carcinoma upregulated long noncoding RNA (HULC), identified as an oncogene in cervical cancer, is involved in not only the clinical stage, lymph node metastasis, and depth of cervical invasion but also outcome. In this study, we aimed to investigate the association between 3 polymorphisms (i.e., rs1041279, rs3005167, and rs7770772) in the promoter of HULC and the risk of cervical squamous cell carcinoma (CSCC). The polymorphisms were genotyped using the multiplex ligase detection reaction assay. The promoter activity was measured using the dual-luciferase reporter assay kit. The rs1041279 GG genotype and G allele revealed a significantly higher risk of CSCC compared with the rs1041279 CC genotype and C allele (GG vs. CC, adjusted OR = 1.79, 95% CI, 1.17-2.73, P = 0.007; G vs. C, adjusted OR = 1.36, 95% CI, 1.09-1.69, P = 0.006). Haplotype analysis revealed that the rs3005167C-rs7770772G-rs1041279C or rs3005167C-rs7770772G-rs1041279G haplotype had a significantly higher risk of CSCC compared to the rs3005167G-rs7770772G-rs1041279C haplotype (CGC vs. GGC, OR = 2.38, 95% CI, 1.53-3.75, P < 0.001; CGG vs. GGC, OR = 3.76, 95% CI, 2.12-6.68, P < 0.001). Dual-luciferase reporter assay showed that the rs1041279 G promoter resulted in higher transcriptional activity compared with the rs1041279 C (P < 0.01). Additionally, the rs1041279 GG genotype carriers had an increased level of HULC expression (P = 0.03). These findings suggest that the HULC rs1041279 may be a useful marker for the etiology of CSCC.

4.
Reprod Sci ; 27(1): 46-54, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32046406

RESUMO

Chemokine CXCL12 and its receptors CXCR4/CXCR7 play a pivotal role in many physiological and pathological situations, while the expression and function in human term trophoblast cells remain largely unknown. In the study, the expression and function of CXCL12 and its receptors CXCR4/CXCR7 in human term trophoblast cells were investigated. Immunocytochemistry and flow cytometry showed that the expression of CXCL12/CXCR4/CXCR7 could be detected in term trophoblast cells while expression level differed. The secretion of CXCL12 in human term trophoblast cells was confirmed by enzyme-linked immunosorbent assay (ELISA). In order to reveal the function of CXCL12, exogenetic recombinant human CXCL12 protein (rhCXCL12) was added to the cultured term trophoblast cells; results showed that cell proliferation ability was increased while cell apoptosis rate was decreased. Moreover, the effects of rhCXCL12 on term trophoblast cells could be diminished or attenuated by antibodies against CXCL12, CXCR4, or CXCR7, respectively. Therefore, these results revealed the important role of CXCL12 on human term trophoblast cells. Our study will provide new insights into understanding the role of CXCL12 on human term trophoblast cells.

5.
J Forensic Sci ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31923319

RESUMO

Methyl nitrite is suggested to cause methemoglobinemia by generating methemoglobin, which may be lethal when the methemoglobin concentration exceeds 70%. However, intoxication with methyl nitrite is seldom reported compared with that with other nitrites. Here, we present an industrial accident involving methyl nitrite inhalation during its synthesis process that resulted in three fatalities and one survivor. The autopsy revealed conspicuous blue-gray discoloration in various parts of the body, including the skin, airway mucosa, vessels, brain, heart, and among other areas. The toxicological tests on the deceased showed methemoglobin concentrations in the blood over the lethal level and increased nitrite ion levels in the blood, gastric contents, liver, and lung tissue compared with those in control samples. The cause of death was determined to be methemoglobinemia-induced hypoxia due to methyl nitrite inhalation. This report provides evidence that in methyl nitrite intoxication, exposure duration has a significant influence on the postmortem changes and likelihood of a fatal outcome may be related to the age of the victim. More attention is required regarding the industrial hazards of this substance.

6.
Int J Legal Med ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31802193

RESUMO

Custodial deaths refer to the death of an individual who is in prison, a detention center, or a police station. The present study aims to retrospectively analyze cases of custodial deaths examined at Tongji Medico Legal Expertise Center in Hubei (TMECH). A total of 172 out of 5853 cases were screened at TMECH from January 1999 to December 2016. Male preponderance was observed in 172 cases (male-female ratio: 5:1). Natural deaths accounted for the majority (70.93%), followed by suicide (16.28%), accidents (3.49%), homicides (4.65%), and undetermined causes (4.65%). The most common natural cause was cardiovascular disease. Custodial deaths occurred more frequently in prisons and detention houses than in police cells (63%, 63%, and 46%, respectively). Among the 172 cases, 105 deaths occurred after resuscitation failure despite the individual being sent to the hospital. The average age across cases was 36.3 years, and 90% of the deceased were aged under 50 years. Since there is no officially reported data regarding the prevalence of causes and manners of custodial deaths in China, our analysis contributes to enhancing the understanding of such deaths in central China and serves as a reference for law enforcement to develop a prevention program to reduce incidents of mortality in custody.

7.
Med Sci Monit ; 25: 5356-5368, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31323016

RESUMO

BACKGROUND B-cell lymphoma 2 (BCL-2) ovarian killer (BOK) is a Bcl-2 family member with sequence homology to pro-apoptotic BAX and BAK, but its physiological and pathological roles remain largely unclear. Exposure of cells to cadmium may cause DNA damage, decrease DNA repair capacity, and increase genomic instability. MATERIAL AND METHODS The present study investigated the effects of BOK on the toxicity of cadmium chloride (CdCl2) to human bronchial epithelial (16HBE) cells. We constructed BOK over-expressing (16HBE-BOK) cells and BOK knockdown (16HBE-shBOK) cells using the BOK-ORF plasmid and BOK-siRNA. qRT-PCR for BOK mRNA expression. We used Trypan blue exclusion assay for cell growth, MTT colorimetric assays for cells inhibition rate, and Comet assays for detecting damaged DNA. RESULTS CdCl2, at various concentrations and exposure times, increased BOK mRNA. 16HBE-BOK cells (BOK over-expressing) proliferated more than 16HBE cells after 72 h; 16HBE-shBOK (BOK knockdown) cells proliferated less. In addition, BOK deficiency enhanced cell death induced by CdCl2. Similarly, CdCl2- and H2O2-induced DNA damage was greater in BOK-deficient cells. CONCLUSIONS These findings support a role for BOK in CdCl2-induced DNA damage and cell death.

8.
Biosci Rep ; 39(7)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31160483

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common cancers globally. An increasing body of evidence has demonstrated the critical function of microRNAs (miRNAs) in the initiation and progression of human cancers. Here, we showed that miR-505 was down-regulated in HCC tissues and cell lines. Reduced expression of miR-505 was significantly correlated with the worse prognosis of HCC patients. Overexpression of miR-505 suppressed the proliferation, colony formation and induced apoptosis of both HepG2 and Huh7 cells. Further mechanism study uncovered that miR-505 bound the 3'-untranslated region (3'-UTR) of the insulin growth factor receptor (IGF-1R) and inhibited the expression of IGF-1R in HCC cells. The down-regulation of IGF-1R by miR-505 further suppressed the phosphorylation of AKT at the amino acid S473. Consistently, the abundance of glucose transporter (GLUT) 1 (GLUT1) was reduced with the overexpression of miR-505. Down-regulation of GLUT1 by miR-505 consequently attenuated the glucose uptake, lactate production and ATP generation of HCC cells. Collectively, our results demonstrated the tumor suppressive function of miR-505 possibly via inhibiting the glycolysis of HCC cells. These findings suggested miR-505 as an interesting target for designing anti-cancer strategy in HCC.

9.
Medicine (Baltimore) ; 98(23): e15788, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31169678

RESUMO

Data based on forensic autopsy in neonates and infants in China are rare in the literature. The purpose of this study is to evaluate the characteristics of fetal, neonatal, and infant death and to determine the main cause of death among them.A retrospective analysis of fetal and infant forensic autopsies referred to the Tongji Forensic Medical Center (TFMC) in Hubei, central China, during a 16-year period between January 1999 and December 2014, was performed.In this period, there were 1111 males and 543 females; the total male-to-female ratio (MFR) was 2.05:1. There were 173 fetal and infant autopsies conducted, comprised of 43 fetal, 84 neonatal (<28 days) and 46 infant (4 weeks to 1 year) cases. The annual case number ranged from 5 in 2004 to 18 in 2014 (annual mean of 10.8). MFR was 1.75:1. About 94% of these deaths (163/173) resulted from natural causes, 6 cases (3.5%) were accidental deaths, and 4 (2.3%) resulted from homicide (4 abandoned babies). Among fetuses, the most common causes of death were placental and umbilical cord pathologies (28%, 12/43), followed by intrapartum asphyxia resulting from amniotic fluid aspiration (AFA) or meconium aspiration syndrome (MAS) (18.6%, 8/43), congenital malformation (14%, 6/43), and intrapartum infection (9.3%, 4/43). A majority of neonatal deaths (66.7%, 56/84) died within 24 hours of birth. The main causes of neonatal death were asphyxia resulting from AFA, MAS, or hyaline membrane disease, and congenital malformation. The main causes of infant (1-12 months) death were infectious diseases, including pneumonia, meningitis, and viral brainstem encephalitis.This study was the 1st retrospective analysis of autopsies of fetal, neonatal, and infant death in TFMC and central China. We delineate the common causes of early demise among cases referred for autopsy, and report a male preponderance in this population. Our data observed that placental and/or umbilical cord pathology, asphyxia due to AFA, and/or MAS, and pneumonia were the leading causes of fetal, neonatal, and infant death, respectively. And it can inform clinical practitioners about the underlying causes of some of the most distressing cases in their practices.


Assuntos
Morte Fetal/etiologia , Doenças Fetais/mortalidade , Morte do Lactente/etiologia , Doenças do Recém-Nascido/mortalidade , Morte Perinatal/etiologia , Asfixia Neonatal/mortalidade , Autopsia , Causas de Morte , China , Feminino , Patologia Legal , Humanos , Lactente , Recém-Nascido , Masculino , Síndrome de Aspiração de Mecônio/mortalidade , Pneumonia/mortalidade , Gravidez , Estudos Retrospectivos
10.
Gynecol Endocrinol ; 35(12): 1059-1062, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31185760

RESUMO

To evaluate the feasibility and clinical value of three-dimensional ultrasound in evaluating ovarian function in perimenopausal women. In this prospective cohort study, 102 patients with clinically suspected perimenopause and 90 patients with menopause were enrolled. These patients were classified into three groups according to the level of follicle stimulating hormone (FSH) and estradiol (E2): menopause group, perimenopause group, and normal group. Perimenopause group: There were significant differences in volume, vascularization index (VI), flow index (FI), and vascularization-flow index (VFI) in the ovaries after treatment. Cycle 1 > cycle 0 (p < .05) and cycle 3 cycle 0 (p < .05), and in FSH: cycle 3 < cycle 0 (p < .05). Three-dimensional ultrasound in ovarian quantitative measurement can objectively reflect the change in the ovarian function, predicting the effect of drug treatment, and provided an objective information for early intervention to menopausal.

11.
Cancer Biother Radiopharm ; 34(7): 472-479, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31135177

RESUMO

Background: MiR-15a-3p has been reported as a tumor suppressor in several kinds of cancer, including cervical cancer and gastric cancer. However, the precise molecular mechanisms underlying its role in prostate cancer (PCa) remain largely unknown. Methods: The expression of miR-15a-3p was determined in PCa tissues and cell lines using quantitative real time PCR. The biological function of miR-15a-3p in PCa cells was investigated using a MTT assay, Edu staining and transwell assay. Moreover, luciferase reporter assay, quantitative real time PCR and western blotting were used to identify and verify the direct downstream target of miR-15a-3p. Results: We found that the expression of miR-15a-3p was down-regulated in both PCa tissues and cell lines. The in vitro results showed that miR-15a-3p overexpression suppressed cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) via down-regulating Wnt/ß-catenin signaling in PCa cells. Moreover, SLC39A7 was a direct downstream target of miR-15a-3p. Furthermore, SLC39A7 overexpression attenuated the effects of miR-15a-3p on cell proliferation, invasion, Wnt/ß-catenin pathway and EMT molecules. Conclusions: In summary, our study indicated that miR-15a-3p inhibited the proliferation, invasion, and EMT process of PCa cells via targeting SLC39A7 and suppressing Wnt/ß-catenin signaling pathway, which may represent a new therapeutic objective for PCa treatment.


Assuntos
MicroRNAs/metabolismo , Neoplasias da Próstata/genética , Via de Sinalização Wnt/genética , Proliferação de Células , Regulação para Baixo , Humanos , Masculino , Invasividade Neoplásica , Neoplasias da Próstata/patologia , Transfecção
12.
Front Oncol ; 9: 313, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31106148

RESUMO

Multidrug resistance (MDR) is one of the leading causes of treatment failure in cancer chemotherapy. One major mechanism of MDR is the overexpressing of ABC transporters, whose inhibitors hold promising potential in antagonizing MDR. Glesatinib is a dual inhibitor of c-Met and SMO that is under phase II clinical trial for non-small cell lung cancer. In this work, we report the reversal effects of glesatinib to P-glycoprotein (P-gp) mediated MDR. Glesatinib can sensitize paclitaxel, doxorubicin, colchicine resistance to P-gp overexpressing KB-C2, SW620/Ad300, and P-gp transfected Hek293/ABCB1 cells, while has no effect to their corresponding parental cells and negative control drug cisplatin. Glesatinib suppressed the efflux function of P-gp to [3H]-paclitaxel and it didn't impact both the expression and cellular localization of P-gp based on Western blot and immunofluorescent analysis. Furthermore, glesatinib can stimulate ATPase in a dose-dependent manner. The docking study indicated that glesatinib interacted with human P-gp through several hydrogen bonds. Taken together, c-Met/SMO inhibitor glesatinib can antagonize P-gp mediated MDR by inhibiting its cell membrane transporting functions, suggesting new application in clinical trials.

13.
Mol Brain ; 12(1): 50, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-31088565

RESUMO

Neonatal seizures are different from adult seizures, and many antiepileptic drugs that are effective in adults often fail to treat neonates. Here, we report that gluconate inhibits neonatal seizure by inhibiting CLC-3 chloride channels. We detect a voltage-dependent outward rectifying Cl- current mediated by CLC-3 Cl- channels in early developing brains but not adult mouse brains. Blocking CLC-3 Cl- channels by gluconate inhibits seizure activity both in neonatal brain slices and in neonatal animals with in vivo EEG recordings. Consistently, neonatal neurons of CLC-3 knockout mice lack the outward rectifying Cl- current and show reduced epileptiform activity upon stimulation. Mechanistically, we demonstrate that activation of CLC-3 Cl- channels alters intracellular Cl- homeostasis and enhances GABA excitatory activity. Our studies suggest that gluconate can suppress neonatal seizure activities through inhibiting CLC-3 Cl- channels in developing brains.

14.
J Clin Pharm Ther ; 44(4): 603-610, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30883843

RESUMO

WHAT IS KNOWN AND OBJECTIVE: The roles of pharmacists in medication management for transplant recipients have received limited attention. This study comprehensively assessed the impact of pharmacist-led post-transplant medication management. METHODS: A retrospective pre- and post-intervention study was conducted in the urology ward in a general hospital. Patients receiving kidney transplants from May 2015 to April 2017 were enrolled. Eligible subjects were assigned into two groups (pre-intervention group and post-intervention group) according to the date (1 May 2016) when the pharmacist commenced participation in the post-transplant management for kidney transplant recipients. The outcomes included intervention analysis, cost-saving effect, outcomes of immunosuppressive drug level monitoring, antibiotic outcomes, safety outcomes, and blood pressure (BP) and plasma glucose (PG) outcomes. RESULTS AND DISCUSSION: A total of 299 patients were admitted to our hospital for kidney transplantation. Two hundred and four patients met inclusion criteria for this study (84 patients were in pre-intervention group, and 120 patients were in post-intervention group). Out of 630 pharmacist interventions in the medication order, 97.1% were accepted by the physicians. The average cost of medications per patient decreased from 4661.64 Ren Min Bi (RMB) to 3051.33 RMB. The percentage of patients who maintained tacrolimus (TAC) levels within the target concentration range was higher in the post-intervention group on post-operative day (POD) 7 (75.00% vs 87.50%, P = 0.021). There was a significant decrease in antibiotic use density (AUD) and duration of antibiotic treatment in the post-intervention group. Post-intervention group showed lower levels in systolic blood pressure (SBP) (141.55 ± 14.62 vs 136.04 ± 13.17, P = 0.01) with higher BP control rate (67.50% vs 90.70%, P = 0.00) on discharge day compared to pre-intervention group. WHAT IS NEW AND CONCLUSION: Pharmacists played a comprehensive role in the management of kidney transplant recipients in the inpatient setting, with some evidence of enhanced clinical outcomes.


Assuntos
Conduta do Tratamento Medicamentoso , Serviço de Farmácia Hospitalar/métodos , Adulto , Pressão Sanguínea/efeitos dos fármacos , Feminino , Humanos , Imunossupressores/uso terapêutico , Transplante de Rim/métodos , Masculino , Equipe de Assistência ao Paciente , Farmacêuticos , Estudos Retrospectivos , Tacrolimo/uso terapêutico , Transplantados
15.
Future Med Chem ; 2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30802141

RESUMO

Multidrug resistance (MDR) in cancer remains a critical obstacle for efficient chemotherapy. Many MDR reversal agents have been discovered but failed in clinical trials due to severe toxic effects. Gaseous signaling molecules (GSMs), such as oxygen, nitric oxide, hydrogen sulfide and carbon monoxide, play key roles in regulating cell biological function and MDR. Compared with other toxic chemosensitizing agents, GSMs are endogenous and biocompatible molecules with little side effects. Research show that GSM modulators, including pharmaceutical formulations of GSMs (combined with conventional chemotherapeutic drugs) and GSM-donors (small molecules with GSMs releasing property), can overcome or reverse MDR. This review discusses the roles of these four GSMs in modulating MDR, and summarizes GSMs modulators in treating cancers with drug resistance.

16.
Medicine (Baltimore) ; 97(52): e13846, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30593184

RESUMO

RATIONALE: The kyphosis caused by old osteoporotic vertebral compression fracture usually requires osteotomy to correct it. Various osteotomy techniques have been reported, but each has its own advantages and disadvantages. PATIENT CONCERNS: We reviewed 2 cases of old osteoporotic vertebral compression fractures with kyphosis in our hospital. One patient complained of persistent low-back pain, another patient complained of low-back pain and weakness of both lower extremities. DIAGNOSIS: Old osteoporotic vertebral compression fractures with kyphosis were diagnosed based on computer tomography and magnetic resonance imaging. INTERVENTIONS: We performed modified grade 4 osteotomy for 2 patients. OUTCOMES: Both patients said significant improvement in preoperative symptoms, and x-ray showed that the kyphosis was corrected. Both patients were satisfied with the treatment at the last follow-up, and the kyphosis was not aggravated. LESSONS: Modified grade 4 osteotomy is an effective option for the treatment of old osteoporotic fracture with kyphosis. It can restore the spine sequence and achieve better clinical result.


Assuntos
Fraturas por Compressão/complicações , Cifose/cirurgia , Fraturas por Osteoporose/complicações , Osteotomia/métodos , Fraturas da Coluna Vertebral/complicações , Idoso , Feminino , Humanos , Cifose/etiologia , Masculino
17.
Drug Resist Updat ; 41: 1-25, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30471641

RESUMO

The successful treatment of cancer has significantly improved as a result of targeted therapy and immunotherapy. However, during chemotherapy, cancer cells evolve and can acquire "multidrug resistance" (MDR), which significantly limits the efficacy of cancer treatment and impacts patient survival and quality of life. Among the approaches to reverse MDR, modulating reactive oxidative species (ROS) may represent a strategy to kill MDR cancer cells that are mechanistically diverse. ROS in cancer cells play a central role in regulating and inducing apoptosis, thereby modulating cancer cells proliferation, survival and drug resistance. The levels of ROS and the activity of scavenging/anti-oxidant enzymes in drug resistant cancer cells are typically increased compared to non-MDR cancer and normal cells. Consequently, MDR cancer cells may be more susceptible to alterations in ROS levels. Numerous studies suggest that compounds modulating cellular ROS levels can enhance MDR cancer cell death and sensitize MDR cancer cells to certain chemotherapeutic drugs. In the current review, we discuss the critical and targetable redox-regulating enzymes, including mitochondrial electron transport chain (ETC) complexes, NADPH oxidases (NOXs), enzymes related to glutathione metabolism, glutamate/cystine antiporter xCT, thioredoxin reductases (TrxRs), nuclear factor erythroid 2-related factor 2 (Nrf2), and their roles in regulating cellular ROS levels, drug resistance as well as their clinical significance. We also discuss and summarize the findings in the past decade regarding the efficacy of ROS modulators for the treatment of MDR cancer alone or as sensitizing compounds. Compounds that are efficacious in modulating ROS generation represent a prominent class of drug candidates that warrants evaluation in clinical trials for patients harboring MDR cancers.


Assuntos
Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Animais , Apoptose/efeitos dos fármacos , Desenvolvimento de Medicamentos/métodos , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Neoplasias/patologia , Oxirredução/efeitos dos fármacos , Qualidade de Vida
18.
Medicine (Baltimore) ; 97(42): e12765, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30334963

RESUMO

This study aims to search for a new, economic, convenient, and low recurrence rate operation for the surgical management of pelvic organ prolapse (POP). The clinical value of the operation for treating POP was determined through retrospective case series. The new operation was called, pelvic autologous tissue reconstruction.Women with symptomatic uterine prolapse, who required surgery, were recruited. A total of 97 women [stage III to IV, according to POP quantification (POP-Q) staging] were collected from January 2010 to December 2016. Among these women, 61 women underwent a traditional operation (TO, vaginal hysterectomy and vaginal anterior and posterior wall repair), while the remaining women underwent pelvic autologous tissue reconstruction.First, there was no statistically significant difference in intraoperative blood loss, indwelling urethral catheter time, in-hospital time, and the time of passage of gas through the anus between the pelvic autologous reconstruction (PAR) and TO groups (P > .05). The average operation time in the PAR group was significantly longer than that in the TO group (P < .05). Second, ultrasonic parameters before and after the operation between the 2 groups were compared. The postoperative rotation angle of the urethra (UR), posterior vesicourethral angle (PVA), and bladder neck descent (BND) significantly decreased in the PAR group (P < .05). There was no statistically significant difference in UR between before and 12 months after surgery in the TO group (P > .05). Furthermore, BND increased in the TO group at 12 months after the operation, compared with that at 3 months after the operation (P < .05). There was no significant difference in PVA and UR before the surgery and at 3 and 12 months after the surgery between the 2 groups (P > .05). In addition, BND was significantly smaller in the PAR group than in the TO group at 3 and 12 months after the surgery (P < .05). Third, there was no statistically significant difference in PFIQ-7 and PISG-12 in both groups after surgery.The stability of the pelvic floor structure was better in the PAR group than in the TO group. Furthermore, PAR is better for preventing the occurrence of pelvic floor prolapse and stress urinary incontinence after surgery.


Assuntos
Fáscia/transplante , Prolapso de Órgão Pélvico/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Retalhos Cirúrgicos/transplante , Incontinência Urinária por Estresse/cirurgia , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Duração da Cirurgia , Diafragma da Pelve/cirurgia , Período Pós-Operatório , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento , Bexiga Urinária/cirurgia , Vagina/cirurgia
19.
Front Mol Neurosci ; 11: 287, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30186110

RESUMO

Potassium chloride co-transporter 2 (KCC2), a major chloride transporter that maintains GABAA receptor inhibition in mature mammalian neurons, is down-regulated in the hippocampus during epileptogenesis. Impaired KCC2 function accelerates or facilitates seizure onset. Calpain, with two main subtypes of m- and µ-calpain, is a Ca2+-dependent cysteine protease that mediates the nonlysosomal degradation of KCC2. Although recent studies have demonstrated that calpain inhibitors exert antiepileptic and neuroprotective effects in animal models of acute and chronic epilepsy, whether calpain activation affects seizure induction through KCC2 degradation remains unknown. Our results showed that: (1) Blockade of calpain by non-selective calpain inhibitor MDL-28170 prevented convulsant stimulation induced KCC2 downregulation, and reduced the incidence and the severity of pentylenetetrazole (PTZ) induced seizures. (2) m-calpain, but not µ-calpain, inhibitor mimicked MDL-28170 effect on preventing KCC2 downregulation. (3) Phosphorylation of m-calpain has been significantly enhanced during seizure onset, which was partly mediated by the calcium independent MAPK/ERK signaling pathway activation. (4) MAPK/ERK signaling blockade also had similar effect as total calpain blockade on both KCC2 downregulation and animal seizure induction. The results indicate that upregulated m-calpain activation by MAPK/ERK during convulsant stimulation down regulates both cytoplasm- and membrane KCC2, and in turn facilitates seizure induction. This finding may provide a foundation for the development of highly effective antiepileptic drugs targeting of m-calpain.

20.
Materials (Basel) ; 11(8)2018 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-30126253

RESUMO

Pure rankinite (C3S2) was prepared by calcining a C-S-H gel precursor at a temperature of 1300 °C. The carbonation hardening behavior of the resulting rankinite was revealed by X-ray diffraction (XRD), Fourier transform-infrared (FT-IR) spectroscopy, thermogravimetry and differential thermal analysis (TG/DTA), and scanning electron microscope (SEM) coupled with energy dispersive spectrum (EDS). The results indicate that the pure rankinite can be easily prepared at a lower temperature. The cubic compressive strengths of the resulting rankinite samples reach a value of 62.5 MPa after 24 h of carbonation curing. The main carbonation products formed during the carbonation process are crystalline calcite, vaterite and highly polymerized amorphous silica gels. The formed carbonation products fill the pores and bind to each other, creating a dense microstructure, which contributes to the excellent mechanical strength. These results provide a novel insight into potential recycling of waste concrete powders for prefabricated building products with lower CO2 emissions.

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