ABSTRACT
Paclitaxel (PTX) is a chemotherapeutic agent that is widely used for the treatment of several types of tumors. However, PTX-induced peripheral neuropathy (PIPN) is an adverse effect generally induced by long-term PTX use that significantly impairs the quality of life. Necroptosis has been implicated in various neurodegenerative disorders. Necroptosis of dorsal root ganglion neurons triggers the pathogenesis of PIPN. Therefore, the present study aims to investigate the role of spinal neuronal necroptosis in PIPN. It also explores the potential role of microglial polarization in necroptosis. We established rat models of PIPN via quartic PTX administration on alternate days (accumulated dose: 8 mg/kg). PTX induced obvious neuronal necroptosis and upregulated the expression of receptor-interacting protein kinase (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the spinal dorsal horn. These effects were inhibited with a necroptosis pathway inhibitor, necrostatin-1 (Nec-1). The effect of microglial polarization on the regulation of spinal necroptosis was elucidated by administering minocycline to inhibit PTX-induced M1 polarization of spinal microglia caused by PTX. We observed a significant inhibitory effect of minocycline on PTX-induced necroptosis in spinal cord cells, based on the downregulation of RIP3 and MLKL expression, and suppression of tumor necrosis factor-α and IL-ß synthesis. Additionally, minocycline improved hyperalgesia symptoms in PIPN rats. Overall, this study suggests that PTX-induced polarization of spinal microglia leads to RIP3/MLKL-regulated necroptosis, resulting in PIPN. These findings suggest a potential target for the prevention and treatment of neuropathic pain.
Subject(s)
Neuralgia , Paclitaxel , Rats , Animals , Paclitaxel/adverse effects , Microglia/pathology , Necroptosis , Minocycline/adverse effects , Quality of Life , Neuralgia/chemically inducedABSTRACT
Introduction: Plaque rupture in atherosclerosis contributes to various acute cardiovascular events. As a new sulfide-containing donor, S-propargyl-cysteine (SPRC) has been reported to play a beneficial role in cardioprotection, potentially through its anti-inflammatory, anti-oxidative and anti-atherogenic activities. Our previous study observed an increase in eNOS phosphorylation in endothelial cells. However, it remains unclear whether SPRC influences vascular smooth muscle cells (VSMCs) within the plaque and if this effect contributes to plaque stabilization. Methods: An atherosclerotic unstable plaque mouse model was established by subjecting ApoE-/- mice to tandem stenosis of the right carotid artery along with a Western diet. Daily SPRC administration was conducted for 13 weeks. Plaque morphology and stability were assessed using MRI scanning and histopathological staining. In our in vitro studies, we stimulated human artery vascular smooth muscle cells (HAVSMCs) with platelet-derived growth factor-BB (PDGF-BB), both with and without 100 µM SPRC treatment. Cell phenotype was assessed using both Western blot and Real-time PCR. Cell proliferation was assessed using the BrdU cell proliferation kit and immunofluorescence of Ki-67, while cell migration was measured using scratch wound healing and transwell assay. MiR-143-3p overexpression and knockdown experiments were used to investigate whether it mediates the effect of SPRC on VSMC phenotype. Results and Discussion: SPRC treatment reduced plasma lipid levels, increased collagen content and decreased cell apoptosis in atherosclerotic plaques, indicating improved plaque stability. Both in vivo and in vitro studies elucidated the role of SPRC in preserving the contractile phenotype of VSMCs through up-regulation of miR-143-3p expression. Furthermore, SPRC suppressed the pro-proliferation and pro-migration effects of PDGF-BB on HAVSMCs. Overall, these findings suggest that the inhibitory effect of SPRC on phenotype switch from contractile to synthetic VSMCs may contribute to its beneficial role in enhancing plaque stability.
ABSTRACT
The present study aimed to investigate the protective effect of S-propargyl-cysteine (SPRC) on atherosclerosis progression in mice. A mouse model of vulnerable atherosclerotic plaque was created in ApoE-/- mice by carotid artery tandem stenosis (TS) combined with a Western diet. Macrophotography, lipid profiles, and inflammatory markers were measured to evaluate the antiatherosclerotic effects of SPRC compared to atorvastatin as a control. Histopathological analysis was performed to assess the plaque stability. To explore the protective mechanism of SPRC, human umbilical vein endothelial cells (HUVECs) were cultured in vitro and challenged with oxidized low-density lipoprotein (ox-LDL). Cell viability was determined with a Cell Counting Kit-8 (CCK-8). Endothelial nitric oxide synthase (eNOS) phosphorylation and mRNA expression were detected by Western blot and RT-qPCR respectively. The results showed that the lesion area quantified by en face photographs of the aortic arch and carotid artery was significantly less, plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were reduced, plaque collagen content was increased and matrix metalloproteinase-9 (MMP-9) was decreased in 80 mg/kg per day SPRC-treated mice compared with model mice. These findings support the role of SPRC in plaque stabilization. In vitro studies revealed that 100 μmol/L SPRC increased the cell viability and the phosphorylation level of eNOS after ox-LDL challenge. These results suggest that SPRC delays the progression of atherosclerosis and enhances plaque stability. The protective effect may be at least partially related to the increased phosphorylation of eNOS in endothelial cells.
Subject(s)
Animals , Humans , Mice , Atherosclerosis , Cholesterol/metabolism , Cysteine/pharmacology , Human Umbilical Vein Endothelial Cells/metabolism , Lipoproteins, LDL/pharmacology , Nitric Oxide Synthase Type III/metabolism , Phosphorylation , Plaque, Atherosclerotic/pathologyABSTRACT
Objective: To evaluate the efficacy of neoadjuvant chemotherapy (NACT) in the treatment of locally advanced olfactory neuroblastoma (ONB), and to explore the factors related to the efficacy of NACT. Methods: A total of 25 patients with ONB who underwent NACT in Beijing TongRen Hospital from April 2017 to July 2022 were retrospectively analyzed. There were 16 males and 9 females, with an average age of 44.9 years (ranged 26-72 years). There were 22 cases of Kadish stage C and 3 cases of stage D. After multiple disciplinary team(MDT) discussion, all patients were treated sequentially with NACT-surgery-radiotherapy. Among them, 17 cases were treated with taxol, cis-platinum and etoposide (TEP), 4 cases with taxol, nedaplatin and ifosfamide (TPI), 3 cases with TP, while 1 case with EP. SPSS 25.0 software was used for statistical analysis, and survival analyses were calculated based on the Kaplan-Meier method. Results: The overall response rate of NACT was 32% (8/25). Subsequently, 21 patients underwent extended endoscopic surgery and 4 patients underwent combined cranial-nasal approach. Three patients with stage D disease underwent cervical lymph node dissection. All patients received postoperative radiotherapy. The mean follow-up time was 44.2 months (ranged 6-67 months). The 5-year overall survival rate was 100.0%, and the 5-year disease-free survival rates was 94.4%. Before NACT, Ki-67 index was 60% (50%, 90%), while Ki-67 index was 20% (3%, 30%) after chemotherapy [M (Q1, Q3)]. The change of Ki-67 before and after NACT was statistically significant (Z=-24.24, P<0.05). The effects of age, gender, history of surgery, Hyams grade, Ki-67 index and chemotherapy regimen to NACT were analyzed. Ki-67 index≥25% and high Hyams grade were related to the efficacy of NACT (all P<0.05). Conclusions: NACT could reduce Ki-67 index in ONBs. High Ki-67 index and Hyams grade are clinical indicators sensitive to the efficacy of NACT. NACT-surgery-radiotherapy is effective for patients with locally advanced ONB.
Subject(s)
Male , Female , Humans , Adult , Middle Aged , Aged , Neoadjuvant Therapy/methods , Retrospective Studies , Esthesioneuroblastoma, Olfactory/etiology , Ki-67 Antigen , Paclitaxel , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Nasal Cavity , Nose Neoplasms/therapy , Neoplasm StagingABSTRACT
OBJECTIVES@#To study the effect of improvement in antibiotic use strategy on the short-term clinical outcome of preterm infants with a gestational age of <35 weeks.@*METHODS@#The medical data were retrospectively collected from 865 preterm infants with a gestational age of <35 weeks who were admitted to the Neonatal Intensive Care Unit of Xiangya Hospital of Central South University from January 1, 2014 to December 31, 2016. The improved antibiotic use strategy was implemented since January 1, 2015. According to the time of implementation, the infants were divided into three groups: pre-adjustment (January 1, 2014 to December 31, 2014; n=303), post-adjustment Ⅰ (January 1, 2015 to December 31, 2015; n=293), and post-adjustment Ⅱ (January 1, 2016 to December 31, 2016; n=269). The medical data of the three groups were compared.@*RESULTS@#There were no significant differences among the three groups in gestational age, proportion of small-for-gestational-age infants, sex, and method of birth (P>0.05). Compared with the pre-adjustment group, the post-adjustment I and post-adjustment Ⅱ groups had a significant reduction in the rate of use of antibiotics and the duration of antibiotic use in the early postnatal period and during hospitalization (P<0.05), with a significant increase in the proportion of infants with a duration of antibiotic use of ≤3 days or 4-7 days and a significant reduction in the proportion of infants with a duration of antibiotic use of >7 days in the early postnatal period (P<0.05). Compared with the post-adjustment Ⅰ group, the post-adjustment Ⅱ group had a significant reduction in the duration of antibiotic use in the early postnatal period and during hospitalization (P<0.05), with a significant increase in the proportion of infants with a duration of antibiotic use of ≤3 days and a significant reduction in the proportion of infants with a duration of antibiotic use of 4-7 days or >7 days (P<0.05). Compared with the pre-adjustment group, the post-adjustment I and post-adjustment Ⅱ groups had significantly shorter duration of parenteral nutrition and length of hospital stay (P<0.05). There were gradual reductions in the incidence rates of grade ≥Ⅲ intraventricular hemorrhage (IVH) and late-onset sepsis (LOS) after the adjustment of antibiotic use strategy. The multivariate logistic regression analysis showed that the adjustment of antibiotic use strategy had no effect on short-term adverse clinical outcomes, and antibiotic use for >7 days significantly increased the risk of adverse clinical outcomes (P<0.05).@*CONCLUSIONS@#It is feasible to reduce unnecessary antibiotic use by the improvement in antibiotic use strategy in preterm infants with a gestational age of <35 weeks, which can also shorten the duration of parenteral nutrition and the length of hospital stay and reduce the incidence rates of grade ≥Ⅲ IVH and LOS.
Subject(s)
Humans , Infant , Infant, Newborn , Anti-Bacterial Agents/therapeutic use , Gestational Age , Infant, Newborn, Diseases , Infant, Premature , Intensive Care Units, Neonatal , Retrospective Studies , Sepsis/epidemiologyABSTRACT
Skin wound healing tends to slow down with aging, which is detrimental to both minor wound recovery in daily life and the recovery after surgery. The aim of current study was to explore the effect of histone deacetylase 6 (HDAC6) on wound healing during aging. Cultured human dermal fibroblasts (HDFs) and mouse full-thickness skin wound model were used to explore the functional changes of replicative senescent dermal fibroblasts and the effect of aging on skin wound healing. Scratch wound healing assay revealed significantly decreased migration speed of senescent HDFs, and BrdU incorporation assay indicated their considerably retardant proliferation. The protein expression levels of collagen and HDAC6 were significantly decreased in both senescent HDFs and skin tissues from aged mice. HDAC6 activity inhibition with highly selective inhibitor tubastatin A (TsA) or HDAC6 knockdown with siRNA decreased the migration speed of HDFs and considerably suppressed fibroblast differentiation induced by transforming growth factor-β1 (TGF-β1), which suggests the involvement of HDAC6 in regulating fundamental physiological activities of dermal fibroblasts. In vivo full-thickness skin wound healing was significantly delayed in young HDAC6 knockout mice when compared with young wild type mice. In addition, the wound healing was significantly slower in aged wild type mice than that in young wild type mice, and became even worse in aged HDAC6 knockout aged mice. Compared to the aged wild type mice, aged HDAC6 knockout mice exhibited delayed angiogenesis, reduced collagen synthesis, and decreased collagen deposition in skin wounds. Together, these results suggest that delayed skin wound healing in aged mice is associated with impaired fibroblast function. Adequate expression and activity of HDAC6 are required for fibroblasts migration and differentiation.
Subject(s)
Humans , Animals , Mice , Aged , Histone Deacetylase 6 , Skin , Wound Healing , Cell Movement , Collagen/pharmacology , Fibroblasts , Mice, Knockout , Cells, CulturedABSTRACT
Objective:To investigate the effect of Ziziphi Spinosae Semen (ZSS) and Albiziae Flos (AF) on behavior and endoplasmic reticulum stress endoplasmic reticulum stress protein kinase R-like endoplasmic reticulum kinase (PERK)/activated transcription factor 4 (ATF4)/CCAAT enhancer binding protein (CHOP) pathway in depression model rats, and to explore its antidepressant mechanism. Method:The male SD rats were divided into normal group, model group, ZSS-AF high dose, middle dose and low dose groups (16, 8, 4 g·kg<sup>-1</sup>) and Venlafaxine group (0.008 g·kg<sup>-1</sup>), <italic>n</italic>=15 in each group. Except the normal group, the depression model was established in the rats of other 5 groups by the method of chronic unpredictable mild stress (CUMS) combined with isolated feeding. The normal group and model group were given with distilled water by gavage when modeling, while other groups received corresponding drug by intragastric administration for 21 days. Behavior changes of rats in each group were observed by the open field test and sugar water consumption test on 1<sup>th </sup>and 21<sup>th</sup>day of the experiment. The protein expressions of PERK, CHOP, B-cell lymphoma-2 associated X protein (Bax) and cysteine-containing aspartate-specific proteases-3(Caspase-3) were detected by Western blot(WB), the ultrastructural changes of the hippocampus were observed by transmission electron microscope, the apoptosis of hippocampal neurons was observed by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) method. Result:Compared with the normal group, the scores of open field test and sugar water consumption rate in model group rats decreased (<italic>P</italic><0.01). Compared with the model group, the scores of open field test and water consumption rate increased (<italic>P</italic><0.01) in ZSS-AF groups and Venlafaxine group. Transmission electron microscope showed that the changes of neuronal damage in hippocampal were revealed in the model group, whereas those neuronal damages were relieved in ZSS-AF groups and Venlafaxine group. TUNEL method showed that the number of apoptotic neurons in hippocampal increased in the model group (<italic>P</italic><0.01), but decreased in ZSS-AFgroups and Venlafaxine group (<italic>P</italic><0.01). WB results showed that as compared with the normal group, protein expressions of PERK, CHOP, Bax and Caspase-3 were up-regulated significantly in the model group (<italic>P</italic><0.01), whereas those were down-regulated in ZSS-AF groups and Venlafaxine group (<italic>P</italic><0.05, <italic>P</italic><0.01). Conclusion:The antidepressant effect of ZSS-AF herbal pair may be correlated with the regulation of endoplasmic reticulum stress PERK/ATF4/-CHOP pathway.
ABSTRACT
Atherosclerosis is a chronic inflammatory disease. Cytokine-related research provides an important direction for the prevention and treatment of atherosclerosis. Cytokines, produced by different types of cells and acting on a range of targets, play a key role in the pathogenesis and progression of atherosclerosis. This review summarizes the main pro-inflammatory and anti-inflammatory cytokines related to atherosclerosis and their underlying mechanism. We also outline current anti-atherosclerosis treatments targeting cytokines. The research and treatment prospects of cytokines in the prevention and treatment of atherosclerosis are discussed briefly as well.
Subject(s)
Humans , Anti-Inflammatory Agents/therapeutic use , Atherosclerosis/drug therapy , Cytokines , Inflammation/drug therapyABSTRACT
A 15-day-old boy was admitted to the hospital due to repeated convulsions for 14 days. The main clinical manifestations were uncontrolled seizures, hypoergia, feeding difficulties, limb hypotonia, and bilateral hearing impairment. Clinical neurophysiology showed reduced brainstem auditory evoked potential on both sides and burst-suppression pattern on electroencephalogram. Measurement of very-long-chain fatty acids in serum showed that C26:0 was significantly increased. Genetic testing showed a pathogenic compound heterozygous mutation, c.101C>T(p.Ala34Val) and c.1448_1460del(p.Ala483Aspfs*37), in the
Subject(s)
Humans , Infant, Newborn , Male , Genetic Testing , Muscle Hypotonia , Mutation , Peroxisomal Multifunctional Protein-2/genetics , Protein Deficiency/geneticsABSTRACT
Neonatal chylothorax is a common cause of neonatal congenital pleural effusion and is often caused by the accumulation of chylous fluid in the thoracic cavity due to the rupture of the thoracic duct and its branched lymphatic vessels for a variety of reasons. Neonatal chylothorax caused by malignant tumors is extremely rare, and this is the first case of neonatal mediastinal neuroblastoma with chylothorax in China. The boy was found to have pleural effusion in the left thoracic cavity in the uterus, and experienced apnea at birth, as well as dyspnea and cyanosis as the main manifestations after birth. He was diagnosed with left chylothorax based on conventional biochemical analysis of pleural effusion. After the treatment including persistent chest drainage and symptomatic and supportive treatment, the drainage of the left thoracic cavity reached a volume of 90-180 mL per day. Neonatal refractory chylothorax was considered. Chest radiograph on day 13 after birth showed lesions in the upper left lung field, and contrast-enhanced plain CT scan of the chest suggested the possibility of posterior mediastinal neuroblastoma. The autopsy confirmed giant posterior mediastinal neuroblastoma (poorly differentiated), which involved the C7-T6 spinal canal and the nearby erector spinae, with a small amount of tumor tissue in the liver and both adrenal glands. Mediastinal tumor is considered the underlying cause of chylothorax in this case.
Subject(s)
Female , Humans , Infant, Newborn , Male , China , Chylothorax , Dyspnea , Pleural Effusion , UterusABSTRACT
OBJECTIVE@#To compare the efficacy of domestic and imported caffeine citrate in the treatment of apnea in preterm infants.@*METHODS@#A total of 98 preterm infants with a gestational age of 28 - 0.05). There were no significant differences in the incidence of complications and the mortality rate between the two groups (P>0.05). There was no significant difference in the incidence of adverse effects between the two groups (P>0.05).@*CONCLUSIONS@#The efficacy and safety of domestic caffeine citrate in the treatment of apnea are similar to those of imported caffeine citrate in preterm infants.
Subject(s)
Humans , Infant , Infant, Newborn , Apnea , Drug Therapy , Caffeine , Therapeutic Uses , Citrates , Therapeutic Uses , Double-Blind Method , Infant, Premature , Infant, Premature, Diseases , Prospective StudiesABSTRACT
OBJECTIVE@#To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province.@*METHODS@#The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017.@*RESULTS@#The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (r=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (r=0.196, P<0.01).@*CONCLUSIONS@#Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.
Subject(s)
Humans , Infant , Infant, Newborn , Anti-Bacterial Agents , Birth Weight , Infant, Extremely Low Birth Weight , Intensive Care Units, Neonatal , Surveys and QuestionnairesABSTRACT
@#Since December 2019, an epidemic of novel coronavirus pneumonia (NCP) has occurred in China. How to effectively prevent and control NCP among children with limited resources is an urgent issue to be explored. Under the unified arrangement of the Xiangya Hospital of Central South University, the Department of Pediatrics has formulated an action plan with Xiangya unique model to prevent and control NCP among children according to the current epidemic situation and diagnostic and therapeutic program in China.
ABSTRACT
<p><b>OBJECTIVE</b>Trying to find a useful marker to subclassify chronic rhinosinusitis (CRS), ratio of eosinophil in peripheral blood was investigated.</p><p><b>METHODS</b>Histologic characteristics of surgical samples were analyzed in 119 CRS with nasal polyps (CRSwNP) patients, who were classified into eosinophil CRSwNP (ECRSwNP) group and non-ECRSwNP group. Peripheral blood eosinophil percentage, olfactory function, skin prick test, serum total IgE and sinus CT scan in two groups were all examined and analyzed. To evaluate the discriminatory power of eosinophil to diagnose ECRSwNP, the Receiver Operating Characteristic(ROC)curve was analysed.</p><p><b>RESULTS</b>There were significant differences in Ratio of EOS, serum total IgE, and olfactory function scores, between ECRSwNP group and non-ECRSwNP group(mean value were 7.31%: 3.90%, 60.9 IU/L: 28.9 IU/L, 5.8: 0.4 respectively, U value were 620.01, 1020.53 and 1092.52, respectively, all P < 0.05). However, there was no difference in skin prick test between two groups. In CT scan exam, there were no differences in Lund-Mackay scores in frontal sinus, anterior ethmoid sinus, posterior ethmoid sinus, sphenoid sinus and ostiomeatal complex area, but maxillary sinus, between ECRSwNP group and non-ECRSwNP group (U value were 27.5, 23.5, 22.5, 31.5, 28.5, respectively, all P > 0.05, and U value of maxillary sinus was 12.01, P < 0.05 ). Peripheral blood eosinophil percentage and serum total IgE were related with pathology of nasal polyps (r value were 0.55, 0.24, and P value were 0.001, 0.01, respectively), especially blood eosinophilia can be a predictor of ECRSwNP. The area under curve was 0.818 and cutoff value was 5.65%.</p><p><b>CONCLUSIONS</b>ECRSwNP is different from non-ECRSwNP in many clinical features. Peripheral blood eosinophil percentage is consistent with histologic features of ECRS, which is a useful marker as 5.65% in classification of CRS.</p>
Subject(s)
Humans , Chronic Disease , Eosinophils , Ethmoid Sinus , Frontal Sinus , Leukocyte Count , Maxillary Sinus , Nasal Polyps , Paranasal Sinuses , ROC Curve , Rhinitis , Sinusitis , Skin Tests , Tomography, X-Ray ComputedABSTRACT
The new edition of Pharmacology of Chinese Materia Medica has broken through the previous mode of the teaching materials. It classified traditional Chinese medicinal herbs into three categories: the herbs for radical cure depending on syndrome differentiation, the herbs for etiological treatment aimed at pathogenesis, and the herbs for symptomatic treatment, combined diseases differentiation with syndrome differentiation, showing active significance in enlightening, guiding the Chinese medicine theory of combining traditional Chinese and Western medicine's compiling, teaching, learning and research applications.
Subject(s)
Drugs, Chinese Herbal , Medicine, Chinese Traditional , Pharmacology, Clinical , Education , Plants, Medicinal , Teaching MaterialsABSTRACT
This paper reported a case of congenital hyperinsulinism and reviewed the relevant literatures regarding to the etiology, pathogenesis, clinical and pathological features, diagnosis and treatment of this disorder. The baby (male), with gestational age of 36 weeks and birth weight 4,200 g, was delivered by caesarean section. It presented with hypoglycemia immediately after birth (0.8 mmol/L). Through the course of the disease, the baby's blood sugar manifested with 1.2-2.8 mmol/L although glucocorticoid was administered. 10% glucose solutions were intravenously infused at a speed of 10-17 mg/(kg x min) for this patient to retain a stable blood sugar level. The plasma insulin level was 24.13 U/L and blood sugar level was 1.5 mmol/L on day 30 of his life. The ratio of plasma insulin (U/L) and plasma glucose (mg/dL) was 0.89. These results suggest an inappropriate insulin secretion resulting in persistent hypoglycemia in this baby and so it was definitely diagnosed with congenital hyperinsulinism.
Subject(s)
Humans , Infant, Newborn , Male , Blood Glucose , Diagnosis, Differential , Hyperinsulinism , Diagnosis , Therapeutics , Insulin , Bodily Secretions , PrognosisABSTRACT
<p><b>OBJECTIVE</b>To study the effect of 8-chloro-adenosine (8-Cl-Ado) on the sensitivity of human hepatoma and breast cancer cell lines to TRAIL-induced apoptosis in vitro and its mechanisms.</p><p><b>METHODS</b>Recombinant soluble TRAIL (rsTRAIL) or 8-Cl-Ado was used to treat hepatoma cell line BEL-7402 and breast cancer cell line MCF-7 in vitro. MTT assay was used to evaluate cell viability. The effect of cotreatment with rsTRAIL and 8-Cl-Ado was analyzed. NF-kappaB activity reporter plasmid was designed to measure the activity of transcription factor NF-kappaB. After transient transfection with the reporter plasmid, which contains NF-kappaB-responsive elements, into the cell lines, cells were treated with rsTRAIL and/or 8-Cl-Ado, then the activity of the reporter gene luciferase was determined. Different kinds of caspase inhibitors were used to measure the effect of caspases in the rsTRAIL and/or 8-Cl-Ado induced apoptosis.</p><p><b>RESULTS</b>8-Cl-Ado could greatly enhance sensitivity of BEL-7402 and MCF-7 cells to reTRAIL. Treatment with 8-Cl-Ado and rsTRAIL inactivated transcription factor NF-kappaB and induced apoptosis in BEL-7402, but not in MCF-7. Caspase family inhibitor could not prevent apoptosis induced by 8-Cl-Ado and rsTRAIL in BEL-7402 cells, however, it could block apoptosis in MCF-7 cells, indicating that two different apoptosis pathways in MCF-7 and BEL-7402 might exist, one was caspase dependent and the other caspase independent. Moreover, all of the inhibitors of caspse-3, -8 and -9 could not block apoptosis induced by the co-treatment.</p><p><b>CONCLUSION</b>8-chloro-adenosine can enhance the sensitivity of human hepatoma cell line BEL-7402 and breast cancer cell line MCF-7 to rsTRAIL, even though MCF-7 is TRAIL-resistant. 8-Cl-Ado combined with rsTRAIL can trigger different signal pathways in MCF-7 and BEL-7402, which are caspase dependent and independent, respectively.</p>
Subject(s)
Humans , 2-Chloroadenosine , Pharmacology , Apoptosis , Apoptosis Regulatory Proteins , Pharmacology , Breast Neoplasms , Pathology , Carcinoma, Hepatocellular , Pathology , Cell Line, Tumor , Liver Neoplasms , Pathology , Membrane Glycoproteins , Pharmacology , NF-kappa B , Metabolism , TNF-Related Apoptosis-Inducing Ligand , Transfection , Tumor Necrosis Factor-alpha , PharmacologyABSTRACT
To observe the morphological features of endothelial cells and cardiac explants cultured in two- or three-dimensional culture systems, several three-dimensional collagen type I culture systems, such as the in gel, on gel, sandwich model, and the microscope slide model, were used to examine the growth patterns of the cells and explants from heart by using immunofluorescence staining and microscopic observation in the presence or absence of vascular endothelial growth factor (VEGF). In two-dimensional cultures the primary cardiac endothelial cells arrayed into a cobblestone-like structure. When cultured in three-dimensional matrix, the cells were elongated and migrated into the gel, with a phenotype similar to that in the process of angiogenesis and vasculogenesis in vivo. VEGF promoted the process of the endothelial cells transforming into tube-like structure. Cardiac explants grew well in the collagen gel. Adjacent explants were connected to each other by the migrating cells with the occurrence of autorhythmic beating of the explants. Thin-layer collagen gel, microscope slide chamber and aorta-strip model were also tested and proved to be good tools for vasculogenesis or angiogenesis studies. Three-dimensional culture systems enable the endothelial cells to proliferate, migrate, and anchor to three-dimensional vascular structures, showing advantages for observing the feature of angiogenesis. Different three-dimensional culture models may be used for variable research purposes.
Subject(s)
Animals , Humans , Male , Rats , Cell Culture Techniques , Methods , Cell Line , Collagen Type I , Pharmacology , Endothelial Cells , Cell Biology , Human Umbilical Vein Endothelial Cells , Cell Biology , Myocardium , Cell Biology , Neovascularization, Physiologic , Physiology , Rats, Sprague-Dawley , Tissue Culture Techniques , Methods , Vascular Endothelial Growth Factor A , Metabolism , PhysiologyABSTRACT
<p><b>OBJECTIVE</b>To explore the role and mechanisms of chemotherapeutic drugs in TRAIL induced cell death.</p><p><b>METHODS</b>Tumoricidal activities of the chemotherapeutic drugs and/or rsTRAIL in 13 strains of tumor cell lines were evaluated by MTS-PMS assay and flow cytometry. DR5 expression in the cells was observed by Western blot.</p><p><b>RESULTS</b>The apoptosis of human promyelocytic leukemia cells HL-60, liver cancer cells BEL-7402, T-acute lymphoblastic leukemia cells Jurkat, and myeloid leukemia cells K562 treated with rsTRAIL at 0.5 microg/ml were 53.20%, 52.20%, 51.54%, 52.70%, and 41.00%, respectively, while that of the embryonal spleen cells 293 was 24.00%. However, the apoptosis percentages of lung cancer cells anti 973, breast cancer cells MCF-7, Chinese hamster ovarian cancer cells COS-7, neuroglialoma cells U251, neuroblastoma cells SH-SY5Y, glioma cells BT-325, rat pheochromocytoma cells PC12, and mouse adrenal epithelial cells NIH3T3 were all less than 10% under the same conditions. The sensitivity of central neuron cells of SH-SY5Y, PC-12, U251, BT3251, and human embryonal spleen cells 293, which were not sensitive to rsTRAIL challenges, increased remarkably after treatment with CHX, CP, and 8-CA at sub-toxic doses plus rsTRAIL at 0.5 microg/ml. The expressions of DR5 were up-regulated and kept pace with the onset of apoptosis in the BEL-7402 liver cancer cells.</p><p><b>CONCLUSION</b>The chemotherapeutic drugs including CHX, CP, and 8-CA at sub-toxic doses can enhance antitumor activity of rsTRAIL.</p>