ABSTRACT
OBJECTIVES: To understand the growth and development status and differences between small for gestational age (SGA) and appropriate for gestational age (AGA) preterm infants during corrected ages 0-24 months, and to provide a basis for early health interventions for preterm infants. METHODS: A retrospective study was conducted, selecting 824 preterm infants who received regular health care at the Guangzhou Women and Children's Medical Center from July 2019 to July 2022, including 144 SGA and 680 AGA infants. The growth data of SGA and AGA groups at birth and corrected ages 0-24 months were analyzed and compared. RESULTS: The SGA group had significantly lower weight and length than the AGA group at corrected ages 0-18 months (P<0.05), while there were no significant differences between the two groups at corrected age 24 months (P>0.05). At corrected age 24 months, 85% (34/40) of SGA and 79% (74/94) of AGA preterm infants achieved catch-up growth. Stratified analysis by gestational age showed that there were significant differences in weight and length at corrected ages 0-9 months between the SGA subgroup with gestational age <34 weeks and the AGA subgroups with gestational age <34 weeks and 34 weeks (P<0.05). In addition, the weight and length of the SGA subgroup with gestational age 34 weeks showed significant differences compared to the AGA subgroups with gestational age <34 weeks and 34 weeks at corrected ages 0-18 months and corrected ages 0-12 months, respectively (P<0.05). Catch-up growth for SGA infants with gestational age <34 weeks and 34 weeks mainly occurred at corrected ages 0-12 months and corrected ages 0-18 months, respectively. CONCLUSIONS: SGA infants exhibit delayed early-life physical growth compared to AGA infants, but can achieve a higher proportion of catch-up growth by corrected age 24 months than AGA infants. Catch-up growth can be achieved earlier in SGA infants with a gestational age of <34 weeks compared to those with 34 weeks.
Subject(s)
Infant, Premature , Infant, Small for Gestational Age , Infant, Newborn , Child , Infant , Female , Humans , Child, Preschool , Gestational Age , Longitudinal Studies , Retrospective StudiesABSTRACT
This paper proposes a vanadium dioxide metamaterial-based tunable, polarization-independent coherent perfect absorber (CPA) in the terahertz frequency range. The designed CPA demonstrates intelligent reconfigurable switch modulation from an ultra-broadband absorber mode to a dual-band absorber mode via the thermally controlled of VO2. The mode of ultra-broadband absorber is realized when the conductivity of VO2 reaches 11850 S/m via controlling its temperature around T = 328â K. In this mode, the CPA demonstrates more than 90% absorption efficiency within the ultra-wide frequency band that extends from 0.1 THz to 10.8 THz. As the conductivity of VO2 reaches 2×105 S/m (T = 340â K), the CPA switches to a dual-band absorber mode where a relatively high absorption efficiency of 98% and 99.7% is detected at frequencies of 4.5 THz and 9.8 THz, respectively. Additionally, using phase modulation of the incident light, the proposed CPA can regulate the absorption efficiency, which can be intelligently controlled from perfect absorption to high pass-through transmission. Owing to the ability of the proposed CPA to intelligently control the performance of light, this study can contribute towards enhancing the performance of stealth devices, all-optical switches and coherent photodetectors.
ABSTRACT
BACKGROUND: The prevalence of lung adenocarcinoma (LUAD) has increased, thus novel biomarkers for its early diagnosis is becoming more important than ever. tRNA-derived small RNA (tsRNA) is a new class of non-coding RNA which has important regulatory roles in cancer biology. This study was designed to identify novel predictive and prognostic tsRNA biomarkers. METHODS: tsRNAs were identified and performed differential expression analysis from 10 plasma samples (6 LUAD and 4 normal, SRP266333) and 96 tissue samples (48 LUAD and 48 normal, SRP133217). Then a tsRNA-mRNA regulatory network was constructed to find hub tsRNAs. Functional enrichment analysis was performed to infer the potential pathways associated with tsRNAs. Afterwards, a Support Vector Machine (SVM) algorithm was used to explore the potential biomarkers for diagnosing LUAD. Lastly, the function of tRF-21-RK9P4P9L0 was explored in A549 and H1299 cell lines. RESULTS: A significant difference of read distribution was observed between normal people and LUAD patients whether in plasma or tissue. A tsRNA-mRNA regulatory network consisting of 155 DEtsRNAs (differential expression tsRNAs) and 406 DEmRNAs (differential expression mRNAs) was established. Three tsRNAs (tRF-16-L85J3KE, tRF-21-RK9P4P9L0 and tRF-16-PSQP4PE) were identified as hub genes with degree > 100. We found Co-DEmRNAs (intersection of DEtsRNAs target mRNAs and differentially expressed mRNAs in LUAD) were engaged in a number of cancer pathways. The AUC of the three hub tsRNAs' expression for diagnosing LUAD reached 0.92. Furthermore, the qPCR validation of the three hub tsRNAs in 37 paired normal and LUAD tissues was consistent with the RNA-Seq results. In addition, tRF-21-RK9P4P9L0 was negatively associated with LUAD prognosis. Inhibition of tRF-21-RK9P4P9L0 expression reduced the proliferation, migration and invasion ability of A549 and H1299 cell lines. CONCLUSION: These findings will help us further understand the molecular mechanisms of LUAD and contribute to novel diagnostic biomarkers and therapeutic target discovery.
ABSTRACT
In the present study, we screened multiple melanoma cell lines for treatment of Apigenin and miRNA expression, also studied the role of miR-512-3p in melanoma. RT-PCR analysis was done for screening miRNA in melanoma cell lines (WM1361B, WM983A, WM1341D, SK-MEL-3, SH-4, SK-MEL-24 and RPMI-7951) compared to normal human epidermal melanocytes. Colony formation assay for cell viability studies, cell cycle by flowcytometry and protein expression by immunoblot analysis. For in vivo analysis tumour xenograft mouse model was created. Immunohistochemistry was done for PCNA positive cells. For expression of miR-512-3p in tumour tissues fluorescence in situ hybridization was done. In silico studies were done by molecular docking studies. The WM1361B and WM983A cell lines showed overexpression of miR-512-3p and increased cell proliferation compared to normal human epidermal melanocytes. Treatment of anti-miR-512-3p to WM1361B and WM983A cells halted cell proliferation and also caused G1-phase arrest. We studied the effect of Apigenin on the expression levels of miR-512-3p and associated molecular targets. Apigenin treatment in WM1361B and WM983A cells showed inhibition in expression of miR-512-3p, arrest of G1 phase of cell cycle, cytotoxicity and revival of p27 Kip1. Apigenin treatment significantly suppressed the growth of WM1361B in tumour induced mice, the activity was associated with decreased levels of miR-512-3p, tumour cell proliferation and increased levels of p27 Kip1 protein. Docking studies confirm potential affinity of Apigenin for p27 Kip1. Apigenin acts as an inhibitor of miR-512-3p by suppressing growth of melanoma both in vitro and in vivo targeting the p27 Kip1 axis.
Subject(s)
Melanoma , MicroRNAs , Animals , Apigenin/pharmacology , Cell Cycle , Cell Proliferation , Cyclin-Dependent Kinase Inhibitor p27/genetics , Cyclin-Dependent Kinase Inhibitor p27/metabolism , G1 Phase , Humans , In Situ Hybridization, Fluorescence , Melanoma/drug therapy , Melanoma/genetics , Melanoma/metabolism , Mice , MicroRNAs/metabolism , Molecular Docking SimulationABSTRACT
BACKGROUND: Bladder cancer (BC) is the fourth most prevalent neoplasm in men and is associated with high tumour recurrence rates, leading to major treatment challenges. Lysine-specific demethylase 6A (KDM6A) is frequently mutated in several cancer types; however, its effects on tumour progression and clinical outcome in BC remain unclear. Here, we explored the potential role of KDM6A in regulating the antitumor immune response. METHODS: We mined The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases for somatic mutation and clinical data in patients with BC. RESULTS: We found frequent mutations in 12 genes in both cohorts, including TP53, KDM6A, CSMD3, MUC16, STAG2, PIK3CA, ARID1A, RB1, EP300, ERBB2, ERBB3, and FGFR3. The frequency o KDM6A mutations in the TCGA and ICGC datasets was 25.97 and 24.27%, respectively. In addition, KDM6A mutation was associated with a lower number of tumour-infiltrating immune cells (TIICs) and indicated a state of immune tolerance. KDM6A mutation was associated with lower KDM6A mRNA level compared with that in samples carrying the wild-type gene. Further, survival analysis showed that the prognosis of patients with low KDM6A expression was worse than that with high KDM6A expression. Using the CIBERSORT algorithm, Tumor Immune Estimation Resource site, and Gene Set Enrichment Analysis, we found that KDM6A mutation downregulated nine signalling pathways that participate in the immune system and attenuated the tumour immune response. CONCLUSION: Overall, we conclude that KDM6A mutation is frequent in BC and promotes tumour immune escape, which may serve as a novel biomarker to predict the immune response.
Subject(s)
Gene Expression Regulation, Neoplastic/immunology , Histone Demethylases/genetics , Tumor Escape/genetics , Urinary Bladder Neoplasms/immunology , Datasets as Topic , Follow-Up Studies , Histone Demethylases/metabolism , Humans , Mutation , Prognosis , Signal Transduction/genetics , Signal Transduction/immunology , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology , Urinary Bladder/immunology , Urinary Bladder/pathology , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/mortalityABSTRACT
While expanded polystyrene (EPS) microplastics have been widely recognized as one of the most important components of plastic litter in the intertidal zones of the global ocean, our understanding of their environmental fate on island beaches is insufficient. In this study, we intended to reveal that the latest EPS microplastic pollution status on 5 island beaches in the Pearl River Estuary, China, by comprehensively assessing the abundance, distribution, size, surface texture and carrying capacity of heavy metals (Cd, As, Cr, Ni, Cu, Pb, Mn, Fe, Al). High level of EPS microplastic abundance ranged from 328 to 82,276 particles m-2 was found, with the highest abundance at Guishan Island and the lowest at Dong'ao Island. Spatial distribution of EPS microplastic abundance was significantly different among different islands. EPS microplastics in the size range of 1-2 mm were the most abundant. The content of heavy metals in EPS microplastics collected on the beaches was greater than that in the new EPS products. The average concentrations of heavy metals in EPS microplastics from 5 islands are Cd (0.27 ± 0.19 µg g-1), As (5.50 ± 3.84 µg g-1), Cr (14.9 ± 8.25 µg g-1), Cu (15.0 ± 7.66 µg g-1), Ni (17.2 ± 17.6 µg g-1), Pb (24.8 ± 7.39 µg g-1), Mn (730 ± 797 µg g-1), Fe (8340 ± 4760 µg g-1), and Al (9624 ± 6187 µg g-1), respectively. The correlation between heavy metals in EPS microplastics and sediments was better than that between heavy metals in EPS microplastics and seawater. The study results indicated that EPS microplastics could act as a carrier for the transport of heavy metals, which might pose a threat to biological and human health.
Subject(s)
Metals, Heavy , Water Pollutants, Chemical , China , Conservation of Natural Resources , Environmental Monitoring , Estuaries , Geologic Sediments , Humans , Metals, Heavy/analysis , Microplastics , Plastics , Polystyrenes/analysis , Rivers , Water Pollutants, Chemical/analysisABSTRACT
In mammalian cells, signaling pathways triggered by TNF can be switched from NF-κB activation to apoptosis and/or necroptosis. The in vivo mechanisms underlying the mutual regulation of these three signaling pathways are poorly understood. In this article, we report that the embryonic lethality of RelA-deficient mice is partially prevented by the deletion of Rip3 or Mlkl, but it is fully rescued by the combined ablation of Fadd and Rip3 or Mlkl or by blocking RIP1 kinase activity (RIP1K45A). RelA-/-Fadd-/-Rip3-/- triple-knockout (TKO) and RelA-/-Rip1K45A/K45A mice displayed bacterial pneumonia leading to death â¼2 wk after birth. Moreover, RelA-/-Rip1K45A/K45A mice, but not TKO mice, developed severe inflammation associated with inflammatory skin lesion. Antibiotic treatment improved bacterial pneumonia, extended the lifespan of TKO and RelA-/-Rip1K45A/K45A mice, and alleviated skin inflammation in RelA-/-Rip1K45A/K45A mice. These results show the mechanisms underlying the in vivo mutual regulation between NF-κB activation and the cell death pathway and provide new insights into this interplay in embryonic development and host immune homeostasis.
Subject(s)
Embryo Loss/genetics , Pneumonia/immunology , Transcription Factor RelA/genetics , Animals , Apoptosis/genetics , Cells, Cultured , Fas-Associated Death Domain Protein/genetics , Fas-Associated Death Domain Protein/metabolism , Female , Immunity , Inflammation , Mice , Mice, Knockout , NF-kappa B/metabolism , Necrosis/genetics , Pneumonia/genetics , Pregnancy , Protein Kinases/genetics , Protein Kinases/metabolism , Signal Transduction , Transcription Factor RelA/metabolism , Transcriptional ActivationABSTRACT
BACKGROUND Glutamate (GLU) is the most excitatory amino acid in the central nervous system and plays an important role in maintaining the normal function of the nervous system. During cerebral ischemia, massive release of GLU leads to neuronal necrosis and apoptosis. It has been reported that dexmedetomidine (DEX) possesses anti-oxidant and anti-apoptotic properties. The objective of this study was to investigate the effects of DEX on GLU-induced neurotoxicity in PC12 cells. MATERIAL AND METHODS PC12 cells were treated with 20 mM GLU to establish an ischemia-induced injury model. Cell viability was accessed by MTT assay. MDA content and SOD activity were analyzed by assay kits. Apoptosis rate, ROS production, intracellular Ca²âº concentration, and MMP were evaluated by flow cytometry. Western blot analysis was performed to analyze expressions of caspase-3, caspase-9, cyt-c, bax, and bcl-2. RESULTS PC12 cells treated with GLU exhibited reduced cell viability and increased apoptosis rates, which were ameliorated by pretreatment with DEX. DEX significantly increased SOD activity, reduced content of MDA, and decreased production of ROS in PC12 cells. In addition, DEX clearly reduced the level of intracellular Ca²âº and attenuated the decline of MMP. Moreover, DEX notably reduced expressions of caspase-3, caspase-9, cyt-c, and bax and increased expression of bcl-2. CONCLUSIONS Our findings suggest that DEX can protect PC12 cells against GLU-induced cytotoxicity, which may be attributed to its anti-oxidative property and reduction of intracellular calcium overload, as well as its ability to inhibit the mitochondria-mediated apoptotic pathway.
Subject(s)
Apoptosis/drug effects , Dexmedetomidine/pharmacology , Membrane Potential, Mitochondrial/drug effects , Animals , Apoptosis/physiology , Cell Survival/drug effects , Cytochromes c/metabolism , Dexmedetomidine/metabolism , Glucose/metabolism , Glutamic Acid/adverse effects , Glutamic Acid/metabolism , Glutamic Acid/pharmacology , Mitochondria/metabolism , Oxidative Stress/drug effects , PC12 Cells , Protective Agents/pharmacology , Rats , Reactive Oxygen Species/metabolism , Signal Transduction/drug effectsABSTRACT
Aplastic anemia (AA) is a hematologic disease characterized by pancytopenia and hypocellular bone marrow, potentially leading to chronic anemia, hemorrhage, and infection. The China Aplastic Anemia Committee and British Committee for Standards in Haematology guidelines recommend hematopoietic stem-cell transplantation (HSCT) or immunosuppressive therapy (IST) comprising antithymocyte globulin (ATG) with cyclosporine (CsA) as initial treatment for AA patients. With limited epidemiological data on the clinical management of AA in Asia, a prospective cohort registry study involving 22 AA treatment centers in China was conducted to describe the disease characteristics of newly diagnosed AA patients and investigate real-world treatment patterns and patient outcomes. Of 340 AA patients, 72.9, 12.6, and 3.5% were receiving IST, traditional Chinese medicine, and HSCT, respectively, at baseline; only 22.2% of IST-treated patients received guideline-recommended ATG with CsA initially. Almost all patients received supportive care (95.6%) as blood transfusion (97.8%), antibiotics (63.7%), and/or hematopoietic growth factors (58.2%). Overall, 64.8% achieved a partial or complete response, and 0.9% experienced relapse. No new safety concerns were identified; serious adverse events were largely unrelated to the treatment regimen. These results demonstrate the need to identify and minimize treatment barriers to standardize and align AA management in China with treatment guideline recommendations and further improve patient outcomes.
Subject(s)
Anemia, Aplastic , Antilymphocyte Serum/administration & dosage , Cyclosporine/administration & dosage , Hematopoietic Stem Cell Transplantation , Immunosuppression Therapy , Medicine, Chinese Traditional , Registries , Adolescent , Adult , Aged , Aged, 80 and over , Allografts , Anemia, Aplastic/mortality , Anemia, Aplastic/therapy , Child , Child, Preschool , China/epidemiology , Disease-Free Survival , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Prospective Studies , Survival RateABSTRACT
BACKGROUND: As intrapancreatic accessory spleen (IPAS) is rarely encountered during clinical practice, the aim of this review was to summarize the epidemiologic features, the diagnosis and treatment of IPAS. METHODS: MEDLINE and EMBASE were searched for articles reporting on IPAS. Categorical variables were reported as frequency and percentage. Continuous variables were reported as median (range). RESULTS: A total of 105 patients were included, of which 73% were detected incidentally. The male/female ratio was 1.23. The size of IPAS in patients who had previously undergone splenectomy was larger than that of patients without prior splenectomy (2.5 cm vs 1.5 cm; p = 0.020). No preoperative examination was able to make a definite diagnosis for all IPASs. More than half of the patients (55%) received surgical treatment, most of which (87%) were suspected as pancreatic neuroendocrine tumors (p-net) preoperatively. CONCLUSIONS: Although rare, IPAS should be considered in the differential of patients with suspected incidental p-net, especially if there has been a past history of splenectomy. Preoperative diagnosis is important as unnecessary surgery can be avoided. As it is difficult to make a definite diagnosis of IPAS by one single examination, multiple techniques may be required.
Subject(s)
Choristoma/diagnostic imaging , Pancreatic Diseases/diagnostic imaging , Spleen , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Choristoma/epidemiology , Choristoma/surgery , Diagnosis, Differential , Female , Humans , Incidental Findings , Infant , Infant, Newborn , Male , Middle Aged , Neuroendocrine Tumors/diagnosis , Pancreatic Diseases/epidemiology , Pancreatic Diseases/surgery , Pancreatic Neoplasms/diagnosis , Predictive Value of Tests , Prognosis , Young AdultABSTRACT
The nasal type of extranodal natural killer/T-cell lymphoma is a rare aggressive lymphoma with poor prognosis. To discover a successful treatment, we investigated the efficacy and safety of chemotherapy with methotrexate, etoposide, dexamethasone, and polyethylene glycol-asparaginase (MESA). Three cycles of MESA were administered to 46 patients with new or relapsed/refractory natural killer/T-cell lymphoma. Complete response after 3 treatment cycles was 43.5%, the overall response rate was 87%, and 2-year overall survival was 83.4%. Complete response was significantly better for newly diagnosed patients than for patients with relapsed/refractory disease. Patients with newly diagnosed disease had a significantly better overall response rate after 1, but not after 2 or 3 treatment cycles. Overall survival and progression-free survival did not differ over 2 years. Grade 1/2 toxicities were frequent, but MESA was associated with fewer grade 3/4 events or treatment-related deaths. These results will require confirmation in larger prospective trials.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Extranodal NK-T-Cell/diagnosis , Lymphoma, Extranodal NK-T-Cell/drug therapy , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Asparaginase/administration & dosage , Biomarkers , China , Dexamethasone/administration & dosage , Drug Resistance, Neoplasm , Etoposide/administration & dosage , Female , Humans , Immunophenotyping , Kaplan-Meier Estimate , Lymphoma, Extranodal NK-T-Cell/mortality , Male , Methotrexate/administration & dosage , Middle Aged , Neoplasm Staging , Polyethylene Glycols/administration & dosage , Prognosis , Recurrence , Retreatment , Treatment Outcome , Young AdultABSTRACT
CRISPR-Cas9 mediated genome editing system has been developed as a powerful tool for elucidating the function of genes through genetic engineering in multiple cells and organisms. This system takes advantage of a single guide RNA (sgRNA) to direct the Cas9 endonuclease to a specific DNA site to generate mutant alleles. Since the targeting efficiency of sgRNAs to distinct DNA loci can vary widely, there remains a need for a rapid, simple and efficient sgRNA selection method to overcome this limitation of the CRISPR-Cas9 system. Here we report a novel system to select sgRNA with high efficacy for DNA sequence modification by a luciferase assay. Using this sgRNAs selection system, we further demonstrated successful examples of one sgRNA for generating one gene knockout cell lines where the targeted genes are shown to be functionally defective. This system provides a potential application to optimize the sgRNAs in different species and to generate a powerful CRISPR-Cas9 genome-wide screening system with minimum amounts of sgRNAs.
Subject(s)
Clustered Regularly Interspaced Short Palindromic Repeats , Genetic Engineering , RNA, Guide, Kinetoplastida/isolation & purification , Selection, Genetic , Bacterial Proteins , CRISPR-Associated Protein 9 , Endonucleases , Gene Knockout Techniques , HEK293 Cells , HT29 Cells , Humans , Lentivirus , Luciferases/chemistry , RNA, Guide, Kinetoplastida/genetics , TransfectionABSTRACT
BACKGROUND: Knee arthroscopy is a common procedure and is associated with postoperative pain. Intra-articular (IA) injection of morphine for pain control has been widely studied, but its analgesic effect after knee arthroscopy is uncertain. OBJECTIVES: To evaluate the relative effects on pain relief and adverse events of IA morphine given for pain control after knee arthroscopy compared with placebo, other analgesics (local anaesthetics, non-steroidal anti-inflammatory drugs (NSAIDs), other opioids) and other routes of morphine administration. SEARCH METHODS: We searched CENTRAL (The Cochrane Library Issue 4, 2015), MEDLINE via Ovid (January 1966 to May 2015), EMBASE via Ovid (January 1988 to May 2015), and the reference lists of included articles. We also searched the metaRegister of controlled trials, clinicaltrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials. SELECTION CRITERIA: We identified all the randomised, double-blind controlled trials that compared single dose IA morphine with other interventions for the treatment of postoperative pain after knee arthroscopy. We excluded studies with fewer than 10 participants in each group, using spinal or epidural anaesthesia, or assessing the analgesic effect of IA morphine on chronic pain. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the quality of each trial and extracted information on pain intensity, supplementary analgesics consumption and adverse events. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created 'Summary of findings' tables. MAIN RESULTS: We included 28 small, low quality studies (29 reports) involving 2564 participants. Of 20 studies (21 reports) comparing morphine with placebo, nine studies with adequate data were included in the meta-analysis. Overall, the risk of bias was unclear. Overall, the quality of the evidence assessed using GRADE was low to very low, downgraded primarily due to risk of bias, small study size, and imprecision.No statistical difference was found between 1 mg IA morphine and placebo in pain intensity (visual analogue scale (VAS)) at early phase (zero to two hours) (mean difference (MD) -0.50, 95% CI -1.15 to 0.14; participants = 297; studies = 7; low quality evidence), medium phase (two to six hours) (MD -0.47, 95% CI -1.09 to 0.14; participants = 297; studies = 7; low quality evidence) and late phase (six to 30 hours) (MD -0.88, 95% CI -1.81 to 0.04; participants = 297; studies = 7; low quality evidence). No significant difference was found between 1 mg and 2 mg morphine for pain intensity at early phase (MD -0.56, 95% CI -1.93 to 0.81; participants = 105; studies = 2; low quality evidence), while 4 mg/5 mg morphine provided better analgesia than 1 mg morphine at late phase (MD 0.67, 95% CI 0.08 to 1.25; participants = 97; studies = 3; low quality evidence). IA morphine was not better than local anaesthetic agents at early phase (MD 1.43, 95% CI 0.49 to 2.37; participants = 248; studies = 5; low quality evidence), NSAIDs at early phase (MD 0.95, 95% CI -0.95 to 2.85; participants = 80; studies = 2; very low quality evidence), sufentanil, fentanyl or pethidine for pain intensity. IA morphine was similar to intramuscular (IM) morphine for pain intensity at early phase (MD 0.21, 95% CI -0.48 to 0.90; participants = 72; studies = 2; very low quality evidence).Meta-analysis indicated that there was no difference between IA morphine and placebo or bupivacaine in time to first analgesic request. Eleven out of 20 studies comparing morphine with placebo reported adverse events and no statistical difference was obtained regarding the incidence of adverse events (risk ratio (RR) 1.09, 95% CI 0.51 to 2.36; participants = 314; studies = 8; low quality evidence). Seven of 28 studies reported participants' withdrawal. There were not enough data for withdrawals to be able to perform meta-analysis. AUTHORS' CONCLUSIONS: We have not found high quality evidence that 1 mg IA morphine is better than placebo at reducing pain intensity at early, medium or late phases. No statistical difference was reported between IA morphine and placebo regarding the incidence of adverse events. The relative effects of 1 mg morphine when compared with IA bupivacaine, NSAIDs, sufentanil, fentanyl and pethidine are uncertain. The quality of the evidence is limited by high risk of bias and small size of the included studies, which might bias the results. More high quality studies are needed to get more conclusive results.
Subject(s)
Analgesics, Opioid/administration & dosage , Arthroscopy/adverse effects , Knee Joint/surgery , Morphine/administration & dosage , Pain, Postoperative/drug therapy , Analgesia/methods , Anesthetics, Local/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Drug Administration Routes , Humans , Injections, Intra-Articular , Pain Measurement , Randomized Controlled Trials as Topic , Time FactorsABSTRACT
Sepsis-associated encephalopathy (SAE) is characterized as brain dysfunction associated with sepsis. In this study we sought to investigate the effects of resveratrol in mice with SAE, as well as its effects in NLRP3 inflammasome and IL-1ß, which were critical in the pathogenesis of SAE. SAE was induced in mice via cecal ligation and puncture (CLP), and resveratrol was administered at two doses after surgery. Spatial learning memory functions were evaluated by Morris water maze testing. Apoptosis in the hippocampus was quantified using TUNEL assay. Inflammation in the hippocampus was quantified by measuring the levels of microglial activation, NLRP3, and IL-1ß. CLP mice treated with resveratrol demonstrated a better spatial memory during water maze training. The TUNEL assay demonstrated significantly attenuated rates of apoptosis, in resveratrol treated mice, while decreasing the number of iba-1 positive microglia in the hippocampus region. NLRP3 expression and IL-1ß cleavage were well inhibited by resveratrol dose-dependently. The in vitro results showed that in the BV2 cell lines resveratrol prevents ATP induced NLRP3 activation and IL-1ß cleavage, which were reversed by the sirtuin 1 inhibitor, nicotinamide. In conclusion, resveratrol improves the spatial memory in mice with SAE and inhibits the NLRP3/IL-1ß axis in the microglia.
Subject(s)
Interleukin-1beta/metabolism , Microglia/drug effects , Microglia/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Sepsis-Associated Encephalopathy/drug therapy , Sepsis-Associated Encephalopathy/metabolism , Stilbenes/therapeutic use , Animals , Cell Line , Male , Mice , Mice, Inbred C57BL , ResveratrolABSTRACT
Inflammation is a response of body tissues to injury and infection. Compounds that can inhibit inflammation have been shown to have potential therapeutic clinical application. Gambogenic acid (GEA) has potent antitumor and anti-inflammatory activities. Herein, the molecular mechanisms of GEA's anti-inflammatory effect were investigated in lipopolysaccharide (LPS)-stimulated macrophage cells. The results showed that pretreatment with GEA could markedly inhibit interleukin (IL)-1α, IL-1ß, tumor necrosis factor-α, IFN-ß, IL-12b, and IL-23a production in a dose-dependent manner in LPS-induced model. Furthermore, this drug significantly reduced the release of nitric oxide (NO), and impaired the protein level of inducible NO synthase and the cyclooxygenase 2. The finding also showed that the effect of GEA may be related to the suppression of the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathway. These results indicate that GEA could suppress LPS-simulated inflammatory response partially by attenuating NO synthesis and NF-κB and MAPK activation, suggesting that it may become a potent therapeutic agent for the treatment of inflammatory diseases.
Subject(s)
Inflammation/drug therapy , Macrophages/drug effects , Xanthenes/pharmacokinetics , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cell Line , Cell Survival/drug effects , Cells, Cultured , Cyclooxygenase 2/metabolism , Cytokines/metabolism , Drugs, Chinese Herbal/pharmacology , Humans , Inflammation/metabolism , Inflammation/pathology , Inflammation Mediators/metabolism , Lipopolysaccharides/toxicity , MAP Kinase Signaling System/drug effects , Macrophages/metabolism , Macrophages/pathology , Mice , NF-kappa B/metabolism , Nitric Oxide/biosynthesis , Nitric Oxide Synthase Type II/metabolismABSTRACT
Endothelial dysfunction is one of the main pathophysiological processes involved in renal ischemia reperfusion injury. Our previous microarray study demonstrated that miR-98 was upregulated in the kidney with ischemia reperfusion injury (IRI). The present study was performed to investigate whether miR-98 was involved in the regulation of endothelial apoptosis under hypoxia and re-oxygenation (H/R) conditions. The dynamic changes of miR-98 in mouse IRI kidney and H/R HUVECs was measured. HUVECs were treated with HIF-1α siRNA to investigate the role of HIF-1α on miR-98 expression. The potential target genes of miR-98 were predicted by bioinformatics analyses. HUVECs were transfected with miR-98 mimics or inhibitor to confirm the role of miR-98 on the expression of target genes and hypoxia-induced apoptosis. The target gene was finally confirmed by dual-luciferase reporter assay. Both of IRI and H/R induced significantly up-regulation of miR-98 in the ischemic kidney and hypoxic HUVECs. HIF-1α siRNA remarkably down-regulated the expression of miR-98 in both normal and hypoxic HUVECs. The putative target genes of miR-98 included IL-6, IL-10 and caspase-3. MiR-98 mimics significantly inhibit caspase-3 expression in HUVECs, while anti-miR-98 significantly up-regulated it. But no change of IL-6 and IL-10 levels was observed after miRNA transfection. miR-98 protected HUVECs against apoptosis induced by hypoxia, while anti-miR-98 had the reverse effect. Furthermore, the dual-luciferase reporter assay confirmed that miR-98 decreased the luciferase activity by targeting the 3' untranslated region of caspase-3. In conclusion, Renal IRI induces up-regulation of miR-98 dependent on HIF-1α, which protects endothelial cells against apoptosis by targeting caspase-3.
Subject(s)
Apoptosis , Cell Hypoxia , Endothelium, Vascular/pathology , MicroRNAs/physiology , Oxygen/administration & dosage , 3' Untranslated Regions , Animals , Caspase 3/genetics , Caspase 3/metabolism , Endothelium, Vascular/enzymology , Endothelium, Vascular/metabolism , Human Umbilical Vein Endothelial Cells , Humans , Male , Mice , Mice, Inbred C57BLABSTRACT
BACKGROUND: Ginsenoside Rg1, the major effective component of ginseng, possesses a variety of pharmacologic activities. The objective of this study was to investigate the effects of Rg1 on liver ischemia-reperfusion (IR) injury and explore its potential mechanisms. MATERIALS AND METHODS: Liver warm IR injury was achieved by occluding the portal vein and hepatic artery for 1 h followed by 6-h reperfusion. Eighteen mice were equally randomized into three groups: sham group, IR group, and IR plus Rg1 group (n = 6 mice per group). Mice received an intravenous dose of 20 mg/kg Rg1 or an equivalent volume of saline before ischemic insult. Liver samples and serum were collected for analyses. Serum aminotransferase, histopathology, and apoptosis were determined. Cytokines were measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The phosphorylation of nuclear factor kappa B (NF-κB) p65 was assessed by Western blotting. In addition, the effect of Rg1 in a simulated IR model in vitro was also investigated. Rg1 (100 ug/mL and 500 ug/mL) was administered 1 h before hypoxia insult, and then apoptosis was measured after 12-h reperfusion. RESULTS: Liver IR injury led to a dramatic increase in aminopherase activity, apoptosis and necrosis of hepatocytes, and production of proinflammatory cytokines. Pretreatment with Rg1 protected mice from IR-induced liver injury. Treatment with a high-dose Rg1 (500 ug/mL) significantly suppressed apoptosis compared with a lower dose or control (both P < 0.001). Phosphorylation of NF-κB p65 was increased significantly in IR group, and administration with Rg1 suppressed the level of phosphorylation. CONCLUSIONS: Pretreatment of mice with Rg1 reduced hepatocellular apoptosis and inhibited inflammatory response, which was in part through the NF-κB signaling pathway. Rg1 may provide a novel therapeutic strategy for the treatment of IR-induced liver injury.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Apoptosis/drug effects , Ginsenosides/pharmacology , Hepatitis/drug therapy , Reperfusion Injury/drug therapy , Animals , Cell Adhesion Molecules/metabolism , Cytokines/metabolism , Disease Models, Animal , Down-Regulation/drug effects , Down-Regulation/immunology , Drugs, Chinese Herbal/pharmacology , Hepatitis/immunology , Hepatitis/pathology , Macrophages, Peritoneal/cytology , Macrophages, Peritoneal/drug effects , Male , Mice, Inbred C57BL , Necrosis/drug therapy , Reperfusion Injury/immunology , Reperfusion Injury/pathology , Transplantation Immunology/drug effects , Warm IschemiaABSTRACT
BACKGROUND: Acute myeloid leukemia (AML) recurrence is largely a result of multidrug resistance (MDR). We aimed to examine the role of 14-3-3ζ in AML chemosensitivity using HL-60 and vincristine-resistant HL-60/VCR cells. METHODS: The effects of 14-3-3ζ siRNA on the growth and cell cycle progression of HL-60 and HL-60/VCR cells were determined. The effect of 14-3-3ζ siRNA on topotecan (TPT)-induced apoptosis was evaluated by several assays. RESULTS: Compared to HL-60 cells, HL-60/VCR cells had increased 14-3-3ζ mRNA and protein expression. Increased mdr-1 mRNA as well as mdr-1, Bcl-2 and Mcl-1 protein expression were observed in HL-60/VCR cells. In both HL-60 and HL-60/VCR cells, 14-3-3ζ was observed in the cytoplasm and nuclear compartments. 14-3-3ζ siRNA significantly reduced HL-60 and HL-60/VCR cell growth after 48 h and increased the proportion of cells in the G0/G1 phase. Moreover, 14-3-3ζ siRNA significantly increased the sensitivity of both HL-60 and HL-60/VCR cells to TPT, possibly through the inhibition of Bcl-2, Mcl-1 and mdr-1 protein expression. CONCLUSIONS: Silencing of 14-3-3ζ increased the sensitivity of both sensitive and resistant HL-60 cells to TPT-induced apoptosis, possibly through altering the expression of apoptosis-associated proteins, suggesting that it may be a potential target for MDR AML.
Subject(s)
14-3-3 Proteins/physiology , Drug Resistance, Multiple/genetics , Drug Resistance, Neoplasm/genetics , Gene Expression Regulation, Leukemic , HL-60 Cells/enzymology , Neoplasm Proteins/physiology , 14-3-3 Proteins/antagonists & inhibitors , 14-3-3 Proteins/biosynthesis , 14-3-3 Proteins/genetics , ATP Binding Cassette Transporter, Subfamily B , ATP Binding Cassette Transporter, Subfamily B, Member 1/biosynthesis , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Apoptosis/genetics , Apoptosis/physiology , Cell Cycle/drug effects , Cell Cycle/genetics , Gene Expression Profiling , HL-60 Cells/drug effects , Humans , Myeloid Cell Leukemia Sequence 1 Protein/biosynthesis , Myeloid Cell Leukemia Sequence 1 Protein/genetics , Neoplasm Proteins/antagonists & inhibitors , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , Oligonucleotide Array Sequence Analysis , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Proto-Oncogene Proteins c-bcl-2/genetics , RNA Interference , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , RNA, Neoplasm/biosynthesis , RNA, Neoplasm/genetics , RNA, Small Interfering/pharmacology , Subcellular Fractions/metabolism , Topoisomerase I Inhibitors/pharmacology , Topotecan/pharmacology , Vincristine/pharmacologyABSTRACT
OBJECTIVE: To report a case of the implantation of thyroid hyperplastic or neoplastic tissue after endoscopic thyroidectomy and discuss this complication in aspects of prevalence, pathogenesis, protection, and therapies. METHODS: A systematic search of literature from the PubMed database was conducted for identifying eligible studies on implantation of thyroid hyperplastic or neoplastic cells after endoscopic thyroid surgery. RESULTS: Overall, 5 reported cases on patients suffering from endoscopic thyroid surgery with implantation of thyroid hyperplastic or neoplastic cells were included in the systematic review. CONCLUSIONS: Unskilled surgeons, rough intraoperative surgical treatment, scarification or rupture of tumor, contamination of instruments, chimney effect, aerosolization of tumor cells may be associated with the implantation after endoscopic thyroidectomy. To minimize the risk of such complication, we should be more meticulous and strict the endoscopic surgery indications.
Subject(s)
Endoscopy , Hyperplasia/pathology , Thyroid Neoplasms/surgery , Adult , Female , Humans , Thyroid Neoplasms/pathology , Young AdultABSTRACT
OBJECTIVE: To analyze the clinicopathologic and immunohistochemical features of nodular histiocytic/mesothelial hyperplasia (NHMH) and to improve the knowledge of this disease. METHODS: Seven cases of NHMH were collected and the clinicopathologic and immunohistochemical data were analyzed with review of the literature. RESULTS: Seven male patients aged from 1.5 to 5.0 years (mean 2.8). The main clinical symptom was an inguinal mass.Grossly, main pathological changes were the mural nodule or free nodule in lumen, with diameter of 0.1-0.5 cm.Histologically, the tumor cell morphology was relatively single, cohesive polygonal or oval cells which were arranged in solid sheets or nests, usually with ovoid or deeply grooved nuclei and a moderate amount of pale pink cytoplasm in the nodular collection area. The nuclei had delicate chromatin and no obvious atypia, and mitosis was incidentally found. A few scattered lymphocytes were found in the stroma. The cyst wall was lined by a single layer of mesothelial cells.Immunohistochemically, the most cells in nodular lesion were strongly positive for the histiocytic marker CD68, vimentin and α1-antichymotrypsin, while lining mesothelial cells on the wall were positive for calretinin, MC, WT1, CK5/6, CKpan and EMA. CONCLUSIONS: NHMH is a rare and benign tumor-like lesion, and easy to be misdiagnozed, which should be distinguished from neuroendocrine tumors, Langerhans cell histiocytosis, seminoma, mesothelioma and so on. The correct diagnosis of this lesion depends on the clinical characteristics, morphology and immunohistochemistry.