ABSTRACT
PURPOSE: Vertebral compression fractures are often treated with vertebroplasty, and filling the injured vertebrae with bone cement is a key part of vertebroplasty. This meta-analysis was performed to compare the clinical efficacy and safety of mineralized collagen-polymethylmethacrylate (MC-PMMA) and polymethylmethacrylate (PMMA) bone cement in the treatment of vertebral compression fractures by vertebroplasty. METHODS: A computerized search of the published literature on mineralized collagen-polymethylmethacrylate and polymethylmethacrylate bone cement in the treatment of vertebral compression fractures was conducted in the China National Knowledge Infrastructure (CNKI), Wanfang database, PubMed, Embase, and Cochrane Library. The search was carried out from the time the database was created to March 2023 and 2 researchers independently conducted literature searches to retrieve a total of 884 studies, of which 12 were included in this meta-analysis. Cochrane systematic review methods were used to assess the quality of the literature and a meta-analysis was performed using ReviewManager 5.4 software. RESULTS: The results of the present meta-analysis showed that in postoperative adjacent vertebral fractures [OR = 0.25; 95% CI (0.15, 0.41)], postoperative cement leakage [OR = 0.45; 95% CI (0.30, 0.68)], Oswestry Disability Index (ODI) scores in the first 3 days after surgery [OR = -0.22; 95% CI (-0.42, -0.03)], ODI score at 6-12 months postoperatively [OR = -0.65; 95% CI (-0.97, -0.32)], visual analog scale (VAS) score at 6-12 months postoperatively [OR = -0.21; 95% CI (-0.46, 0.04)], and 1-year postoperative CT values [OR = 5.56; 95% CI (3.06, 8.06)], the MC-PMMA bone cement group was superior to the PMMA bone cement group. However, the differences between the two groups were not statistically different in terms of cement filling time, cement filling volume, operation time, intraoperative bleeding, hospitalization time, postoperative (<1 week, 3-6 months) vertebral body posterior convexity Cobb's angle, postoperative (<1 week, 6-12 months) vertebral body anterior margin relative height, postoperative (≤3 days, 1-3 months) pain VAS score and postoperative (1-3 months) ODI score. CONCLUSIONS: Compared with PMMA bone cement, the application of MC-PMMA bone cement is advantageous in reducing postoperative complications (adjacent vertebral fracture rate, cement leakage rate), pain relief, and functional recovery in the long-term postoperative period (>6 months), but there is still a need for more high-quality randomized controlled studies to provide more adequate evidence.
Subject(s)
Fractures, Compression , Kyphoplasty , Osteoporotic Fractures , Spinal Fractures , Vertebroplasty , Humans , Bone Cements/therapeutic use , Bone Cements/chemistry , Collagen , Fractures, Compression/surgery , Kyphoplasty/methods , Osteoporotic Fractures/surgery , Pain/drug therapy , Polymethyl Methacrylate/therapeutic use , Polymethyl Methacrylate/chemistry , Spinal Fractures/surgery , Treatment OutcomeABSTRACT
BACKGROUND: Gene polymorphisms of estrogen receptor (ESR) 1 PvuII (rs2234693), XbaI (rs9340799), G2014A (rs2228480), ESR2 AluI (rs4986938), and RsaI (rs1256049) had been reported to be associated with the risk of osteoporosis. However, these conclusions were inconsistent, therefore, an updated meta-analysis was conducted to further explore these issues. OBJECTIVE: To evaluate the association between gene polymorphisms of ESR1 PvuII (rs2234693), XbaI (rs9340799), G2014A (rs2228480), ESR2 AluI (rs4986938), RsaI (rs1256049), and osteoporosis risk. MATERIALS AND METHODS: PubMed, Medline, Ovid, Embase, CNKI, and China Wanfang databases were searched. Association was assessed using odds ratio with 95% confidence interval. Moreover, the false-positive reporting probability, Bayesian false-finding probability, and Venetian criteria were used to assess the credibility of statistically significant associations. RESULTS: Overall, ESR1 PvuII (rs2234693) and XbaI (rs9340799) were associated with the risk of osteoporosis in Indians. Moreover, ESR1 G2014A (rs2228480) was associated with the decreased risk of osteoporosis in East Asians. Moreover, ESR2 Alul (rs4986938) was associated with the increased risk of osteoporosis in East Asians and Caucasians. There was a significant association between ESR2 Rsal (rs1256049) and osteoporosis risk in overall population. When only high-quality and Hardy-Weinberg equilibrium studies were included in the sensitivity analysis, all results did not change in the present study. When the credibility was evaluated applying false-positive reporting probability, Bayesian false-finding probability, and Venetian criteria, all significant associations were considered as false positive results. CONCLUSIONS: In summary, this study shows that all substantial associations between gene polymorphisms of ESR1 (PvuII, XbaI, and G2014A) and ESR 2 (AluI and RsaI) and osteoporosis risk are possibly false positive results instead of real associations or biological variables.
Subject(s)
Osteoporosis , Humans , Asian People/genetics , Bayes Theorem , Estrogen Receptor alpha/genetics , Estrogen Receptor beta/genetics , Genetic Predisposition to Disease , Osteoporosis/epidemiology , Osteoporosis/ethnology , Osteoporosis/genetics , Polymorphism, Single Nucleotide , East Asian PeopleABSTRACT
Carya cathayensis is an important economic nut tree that is endemic to eastern China. As such, outbreaks of root rot disease in C. cathayensis result in reduced yields and serious economic losses. Moreover, while soil bacterial communities play a crucial role in plant health and are associated with plant disease outbreaks, their diversity and composition in C. cathayensis are not clearly understood. In this study, Proteobacteria, Acidobacteria, and Actinobacteria were found to be the most dominant bacterial communities (accounting for approximately 80.32% of the total) in the root tissue, rhizosphere soil, and bulk soil of healthy C. cathayensis specimens. Further analysis revealed the abundance of genera belonging to Proteobacteria, namely, Acidibacter, Bradyrhizobium, Paraburkholderia, Sphaerotilus, and Steroidobacter, was higher in the root tissues of healthy C. cathayensis specimens than in those of diseased and dead trees. In addition, the abundance of four genera belonging to Actinobacteria, namely, Actinoallomurus, Actinomadura, Actinocrinis, and Gaiella, was significantly higher in the root tissues of healthy C. cathayensis specimens than in those of diseased and dead trees. Altogether, these results suggest that disruption in the balance of these bacterial communities may be associated with the development of root rot in C. cathayensis, and further, our study provides theoretical guidance for the isolation and control of pathogens and diseases related to this important tree species.
Subject(s)
Actinobacteria , Carya , Gammaproteobacteria , Microbiota , Actinobacteria/genetics , Bacteria/genetics , Plant Roots/microbiology , Proteobacteria , Rhizosphere , Soil , Soil Microbiology , TreesABSTRACT
Conjugated microporous polymers (CMP) as porous functional materials have received considerable attention due to their unique structures and fascinating properties for the adsorption and degradation of dyes. Herein, a triazine-conjugated microporous polymer material with rich N-donors at the skeleton itself was successfully synthesized via the Sonogashira-Hagihara coupling by a one-pot reaction. These two polymers had Brunauer-Emmett-Teller (BET) surface areas of 322 and 435 m2g-1 for triazine-conjugated microporous polymers (T-CMP) and T-CMP-Me, respectively. Due to the porous effects and the rich N-donor at the framework, it displayed a higher removal efficiency and adsorption performance compared to cationic-type dyes and selectivity properties for (methylene blue) MB+ from a mixture solution of cationic-type dyes. Furthermore, the T-CMP-Me could quickly and drastically separate MB+ and (methyl orange) MO- from the mixed solution within a short time. Their intriguing absorption behaviors are supported by 13C NMR, UV-vis absorption spectroscopy, scanning electron microscopy, and X-ray powder diffraction studies. This work will not only improve the development of porous material varieties, but also demonstrate the adsorption or selectivity of porous materials for dyes from wastewater.
ABSTRACT
Streptococcus pneumoniae relies on two-component systems (TCSs) to regulate the processes of pathogenicity, osmotic pressure, chemotaxis, and energy metabolism. The TCS01 system of S. pneumoniae is composed of HK01 (histidine kinase) and RR01 (response regulator). Previous studies have reported that an rr01 mutant reduced the pneumococcal virulence in rat pneumonia, bacteremia, a nasopharyngeal model, and infective endocarditis. However, the mechanism of TCS01 (HK/RR01) regulating pneumococcal virulence remains unclear. Here, pneumococcal mutant strains Δrr01, Δhk01, and Δrr01&hk01 were constructed, and bacterial adhesion and invasion to A549 cells were compared. RNA sequencing was performed in D39 wild-type and Δrr01 strains, and transcript profile changes were analyzed. Differentially expressed virulence genes in the Δrr01 strain were screened out and identified by quantitative real-time PCR (qRT-PCR). Our results showed that pneumococcal mutant strains exhibited attenuated adhesion and invasion to A549 cells and differential transcript profiles. Results of qRT-PCR identification showed that the differential virulence genes screened out were downregulated. Among those changed virulence genes in the Δrr01 strain, the downregulated expression level of choline binding protein pcpA was the most obvious. Complementation of rr01 and overexpression of pcpA in the Δrr01 strain partially restored both pneumococcal adhesion and invasion, and rr01 complementation made the expression of pcpA upregulated. These findings revealed that rr01 influenced pneumococcal virulence by regulating pcpA.
Subject(s)
Intracellular Signaling Peptides and Proteins , Pneumococcal Infections , Streptococcus pneumoniae , Streptococcus pneumoniae/genetics , Streptococcus pneumoniae/pathogenicity , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , A549 Cells , Humans , Pneumococcal Infections/metabolism , Pneumococcal Infections/microbiology , Bacterial AdhesionABSTRACT
To study the distribution characteristics and horizontal transfer potential of antibiotic resistance genes in biofilms of water supply pipes made of different materials, the biofilms of 304 and 316 L stainless steel pipes and PPR and PE plastic pipes were analyzed using metagenomic sequencing. The results showed that a total of 146 antibiotic resistance genes belonging to 17 classes were detected in the biofilms. Multidrug resistance genes had the highest abundance and varied a lot in different biofilms, which was the main reason for the differences in antibiotic resistance genes in different biofilms. The total abundance of mobile genetic elements was high in different biofilms, but overall coexistence with antibiotic resistance genes was low, with integrase genes showing a closer relationship with antibiotic resistance genes and possibly playing an important role in the horizontal transfer of antibiotic resistance genes. Different antibiotic resistance genes possessed different genera of potential hosts; highly abundant hosts such as Aquabacterium and Bradyrhizobium were the basis for the presence of a high abundance of multidrug resistance genes. Microbial attachment in different pipe walls was selective, and the primary influence of antibiotic resistance in biofilms was bacterial community composition, followed by the horizontal transfer of genes mediated by mobile genetic elements, community composition, and mobile genetic elements together shaping the distribution characteristics of antibiotic resistance genes.
Subject(s)
Anti-Bacterial Agents , Drinking Water , Anti-Bacterial Agents/pharmacology , Water Supply , Drug Resistance, Microbial/genetics , Bacteria/genetics , Biofilms , Genes, Bacterial , Drinking Water/microbiologyABSTRACT
BACKGROUND: Many middle-aged and older adults have more than one chronic health condition. It is therefore important to explore the effectiveness of interventions for multiple chronic conditions. Tai Chi is widely used in China and other countries, and many studies have examined the effect of Tai Chi on anxiety and depression. However, there are no systematic reviews of the effect of Tai Chi on anxiety and depression in various chronic conditions. This systematic review and meta-analysis aimed to evaluate the effects of Tai Chi on anxiety and depression symptoms in four chronic conditions: cancer, stroke, heart failure (HF), and chronic obstructive pulmonary disease (COPD). METHODS: We searched Chinese and English databases (Cochrane Library, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Database, and Sinomed) from inception to October 2020. Review Manager version 5.2 and Stata version 12.0 were used to perform a systematic review. The quality of the included studies was evaluated using the Cochrane risk of bias tool. The study was registered with the PROSPERO database (number CRD42020209594). RESULTS: Of the 596 studies identified, we included 25 randomized controlled trials involving 1819 participants. Combined analysis of the four diseases showed statistically significant differences between the Tai Chi and control groups for anxiety symptoms (SMD -0.99, 95%CI: -1.5, -0.47; P < 0.01) and depressive symptoms (SMD 0.70, 95%CI: -1.01, -0.39; P < 0.01). Subgroup analyses showed statistically significant differences between the Tai Chi and control groups for depressive symptoms in stroke (SMD -0.43, 95%CI: -0.67, -0.18; P < 0.01) and HF (SMD -0.57, 95%CI: -0.8, -0.33; P < 0.01). However, no statistically significant differences were found for depressive symptoms in COPD or cancer. There were statistically significant differences between the Tai Chi and control groups for anxiety symptoms in stroke (SMD -0.60, 95%CI: -0.88, -0.32; P < 0.01) and cancer (SMD -0.69, 95%CI: -1.22, -0.17; P < 0.01), but not in COPD or HF. Subgroup, sensitivity, meta regression, and publication bias analyses showed high heterogeneity correlated with a single study and study quality. Sensitivity analysis showed that most meta-analysis results had good stability, but those for anxiety symptoms in COPD were unstable; therefore, careful interpretation is required. CONCLUSION: Tai Chi has a positive effect on anxiety and depression, especially for patients with cancer, stroke, and HF. However, given the weak evidence, this approach is not a substitute for psychiatric treatment.
Subject(s)
Heart Failure , Neoplasms , Pulmonary Disease, Chronic Obstructive , Stroke , Tai Ji , Aged , Anxiety/etiology , Anxiety/therapy , Depression/etiology , Depression/therapy , Heart Failure/therapy , Humans , Middle Aged , Neoplasms/complications , Neoplasms/therapy , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/therapy , Quality of Life , Stroke/complications , Stroke/therapyABSTRACT
Background: Congenital hypothyroidism is often caused by genetic mutations that impair thyroid hormone (TH) production, resulting in growth and development defects. XB130 (actin filament associated protein 1 like 2) is an adaptor/scaffold protein that plays important roles in cell proliferation, migration, intracellular signal transduction, and tumorigenesis. It is highly expressed in thyrocytes, however, its function in the thyroid remains largely unexplored. Methods:Xb130-/- mice and their littermates were studied. Postnatal growth and growth hormone levels were measured, and responses to low or high-iodine diet, and levothyroxine treatment were examined. TH and thyrotropin in the serum and TH in the thyroid glands were quantified. Structure and function of thyrocytes in embryos and postnatal life were studied with histology, immunohistochemistry, immunofluorescence staining, Western blotting, and quantitative reverse transcription polymerase chain reaction. Results:Xb130-/- mice exhibited transient growth retardation postnatally, due to congenital hypothyroidism with reduced TH synthesis and secretion, which could be rescued by exogenous thyroxine supplementation. The thyroid glands of Xb130-/- mice displayed diminished thyroglobulin iodination and release at both embryonic and early postnatal stages. XB130 was found mainly on the apical membrane of thyroid follicles. Thyroid glands of embryonic and postnatal Xb130-/- mice exhibited disorganized apical membrane structure, delayed folliculogenesis, and abnormal formation of thyroid follicle lumina. Conclusion: XB130 critically regulates folliculogenesis by maintaining apical membrane structure and function of thyrocytes, and its deficiency leads to congenital hypothyroidism.
Subject(s)
Adaptor Proteins, Signal Transducing/deficiency , Congenital Hypothyroidism/genetics , Microfilament Proteins/deficiency , Thyroid Epithelial Cells/metabolism , Animals , Iodine/administration & dosage , Mice , Thyroid Hormones/blood , Thyroxine/administration & dosage , Thyroxine/pharmacologyABSTRACT
Application of chemotherapeutic oxaliplatin represses gene transcription through induction of DNA methylation, which may contribute to oxaliplatin-induced chronic pain. Here, Ddr1, which showed an increased methylation in the promoter, was screened from the SRA methylation database (PRJNA587622) after oxaliplatin treatment. qPCR and MeDIP assays verified that oxaliplatin treatment increased the methylation in Ddr1 promoter region and decreased the expression of DDR1 in the neurons of spinal dorsal horn. In addition, overexpression of DDR1 by intraspinal injection of AAV-hSyn-Ddr1 significantly alleviated the mechanical allodynia induced by oxaliplatin. Furthermore, we found that oxaliplatin treatment increased the expression of DNMT3b and ZEB1 in dorsal horn neurons, and promoted the interaction between DNMT3b and ZEB1. Intrathecal injection of ZEB1 siRNA inhibited the enhanced recruitment of DNMT3b and the hypermethylation in Ddr1 promoter induced by oxaliplatin. Finally, ZEB1 siRNA rescued the DDR1 downregulation and mechanical allodynia induced by oxaliplatin. In conclusion, these results suggested that the ZEB1 recruited DNMT3b to the Ddr1 promoter, which induced the DDR1 downregulation and contributed to the oxaliplatin-induced chronic pain.
Subject(s)
Chronic Pain/metabolism , DNA Methylation/physiology , Discoidin Domain Receptor 1/genetics , Oxaliplatin/adverse effects , Spinal Cord Dorsal Horn/metabolism , Zinc Finger E-box-Binding Homeobox 1/metabolism , Animals , Chronic Pain/chemically induced , DNA/metabolism , DNA (Cytosine-5-)-Methyltransferases/metabolism , DNA Methylation/drug effects , Down-Regulation/drug effects , Hyperalgesia/chemically induced , Hyperalgesia/metabolism , Male , Neuralgia/chemically induced , Neuralgia/metabolism , Promoter Regions, Genetic/physiology , RNA, Small Interfering/pharmacology , Rats, Sprague-Dawley , Spinal Cord Dorsal Horn/drug effects , Up-Regulation/drug effects , DNA Methyltransferase 3BABSTRACT
To study the effect of combined ultraviolet (UV) chloramine disinfection on viruses in a drinking water supply system, a full-scale experiment was conducted to analyze the distribution, variability, community structure, and hosts of viruses using metagenomics. The results showed that the combined UV chloramine process reduced the number of virus species (6.13%) and gene abundance (51.97%) but did not completely remove the viruses from the water. The United States Environmental Protection Agency (USEPA) report that virus removal efficiencies from water can reach 99%-99.99% based on culturing methods. However, in this study, metagenomic analysis indicated a total virus removal rate of only 93.46%. Therefore, the detection of viruses in water using culturing method cannot reliably detect viruses in drinking water. Caudovirales are the most abundant type of virus in water supply systems and are sensitive to chloramine disinfection. Lentivirus, as a virus that can infect humans and vertebrates, has strong resistance to UV and chloramine disinfection. The main virus hosts in the studied water supply system were bacteria (61.50%). The viruses in the raw water were mainly parasitic in Synechococcus. The dominant virus host was Pseudomonas in both the effluent water and pipe network water. The gene abundance of the Pseudomonas aeruginosa host in the pipe network increased by 342.62%, which requires further attention as a virus risk in pipe network systems. Overall, combined UV chloramine disinfection was more effective at the removal of virus hosts than single UV disinfection (51.97% compared to 0.79%).
Subject(s)
Drinking Water , Viruses , Water Purification , Chloramines/pharmacology , Disinfection , Humans , Ultraviolet Rays , United States , Water SupplyABSTRACT
BACKGROUND: Ex vivo lung perfusion (EVLP) is an isolated organ assessment technique that has revolutionized the field of lung transplantation and enabled a safe increase in the number of organs transplanted. The objective of this study was to develop a protein-based assay that would provide a precision medicine approach to lung injury assessment during EVLP. METHODS: Perfusate samples collected from clinical EVLP cases performed from 2009 to 2019 were separated into development (nâ¯=â¯281) and validation (nâ¯=â¯57) sets to derive and validate an inflammation score based on IL-6 and IL-8 protein levels in perfusate. The ability of an inflammation score to predict lungs suitable for transplantation and likely to produce excellent recipient outcomes (time on ventilator ≤ 3 days) was assessed. Inflammation scores were compared to conventional clinical EVLP assessment parameters and associated with outcomes, including primary graft dysfunction and patient care in the ICU. RESULTS: An inflammation score accurately predicted the decision to transplant (AUROC 68% [95% CI 62-74]) at the end of EVLP and those transplants associated with short ventilator times (AUROC 73% [95% CI 66-80]). The score identified lungs more likely to develop primary graft dysfunction at 72-hours post-transplant (OR 4.0, pâ¯=â¯0.03). A model comprised of the inflammation score and ∆PO2 was able to determine EVLP transplants that were likely to have excellent recipient outcomes, with an accuracy of 87% [95% CI 83-92]. CONCLUSIONS: The adoption of an inflammation score will improve accuracy of EVLP decision-making and increase confidence of surgical teams to determine lungs that are suitable for transplantation, thereby improving organ utilization rates and patient outcomes.
Subject(s)
Extracorporeal Circulation/methods , Inflammation/diagnosis , Lung Injury/diagnosis , Lung Transplantation/statistics & numerical data , Primary Graft Dysfunction/prevention & control , Tissue Donors/statistics & numerical data , Follow-Up Studies , Humans , Lung Injury/etiology , Morbidity/trends , Ontario/epidemiology , Primary Graft Dysfunction/epidemiology , Retrospective StudiesABSTRACT
INTRODUCTION: Transplantation of lungs from donation after circulatory death (DCD) in addition to donation after brain death (DBD) became routine worldwide to address the global organ shortage. The development of ex vivo lung perfusion (EVLP) for donor lung assessment and repair contributed to the increased use of DCD lungs. We hypothesise that a better understanding of the differences between lungs from DBD and DCD donors, and between EVLP and directly transplanted (non-EVLP) lungs, will lead to the discovery of the injury-specific targets for donor lung repair and reconditioning. METHODS: Tissue biopsies from human DBD (n=177) and DCD (n=65) donor lungs, assessed with or without EVLP, were collected at the end of cold ischaemic time. All samples were processed with microarray assays. Gene expression, network and pathway analyses were performed using R, Ingenuity Pathway Analysis and STRING. Results were validated with protein assays, multiple logistic regression and 10-fold cross-validation. RESULTS: Our analyses showed that lungs from DBD donors have upregulation of inflammatory cytokines and pathways. In contrast, DCD lungs display a transcriptome signature of pathways associated with cell death, apoptosis and necrosis. Network centrality revealed specific drug targets to rehabilitate DBD lungs. Moreover, in DBD lungs, tumour necrosis factor receptor-1/2 signalling pathways and macrophage migration inhibitory factor-associated pathways were activated in the EVLP group. A panel of genes that differentiate the EVLP from the non-EVLP group in DBD lungs was identified. CONCLUSION: The examination of gene expression profiling indicates that DBD and DCD lungs have distinguishable biological transcriptome signatures.
Subject(s)
Lung Transplantation , Transcriptome , Extracorporeal Circulation , Humans , Lung , Perfusion , Tissue DonorsABSTRACT
To investigate the ecological mechanisms of the bacterial response to human disturbance in micro-polluted water ecosystems, we studied the relationship between the environmental factors and bacterial community development in the incoming water and various areas of a reservoir based on an ecological null model. The results showed that the phylogenetic clustering of bacterial communities was more dispersed than expected (the single-sample t-test of SES.MNTD has a 95% lower confidence limit of 9.79). Temperature is an important environmental factor affecting community phylogeny. The relative importance of stochastic and deterministic processes in the bacterial community succession of different samples showed seasonal characteristics. The bacterial community succession in spring, summer, and autumn samples was dominated by random and deterministic processes. NH4+-N is the main environmental factor affecting the relative importance of random and deterministic processes. When the concentration of NH4+-N is 0.06-0.40 mg ·L-1, the bacterial community succession is dominated by random processes; when the concentration is 0.40-0.80 mg ·L-1, it is dominated by both random and deterministic processes. Dispersal limitation (61.68%) and heterogeneous selection (26.65%) played important roles in bacterial community changes at different sampling points in the study area.
Subject(s)
Bacteria , Ecosystem , Bacteria/genetics , PhylogenyABSTRACT
BACKGROUND: Although the action mechanism of antineoplastic agents is different, oxaliplatin, paclitaxel, or bortezomib as first-line antineoplastic drugs can induce painful neuropathy. In rodents, mechanical allodynia is a common phenotype of painful neuropathy for 3 chemotherapeutics. However, whether there is a common molecular involved in the different chemotherapeutics-induced painful peripheral neuropathy remains unclear. METHODS: Mechanical allodynia was tested by von Frey hairs following i.p. injection of vehicle, oxaliplatin, paclitaxel, or bortezomib in Sprague-Dawley rats. Reduced representation bisulfite sequencing and methylated DNA immunoprecipitation were used to detect the change of DNA methylation. Western blot, quantitative polymerase chain reaction, chromatin immunoprecipitation, and immunohistochemistry were employed to explore the molecular mechanisms. RESULTS: In 3 chemotherapeutic models, oxaliplatin, paclitaxel, or bortezomib accordantly upregulated the expression of transient receptor potential cation channel, subfamily C6 (TRPC6) mRNA and protein without affecting the DNA methylation level of TRPC6 gene in DRG. Inhibition of TRPC6 by using TRPC6 siRNA (i.t., 10 consecutive days) relieved mechanical allodynia significantly following application of chemotherapeutics. Furthermore, the downregulated recruitment of DNA methyltransferase 3 beta (DNMT3b) at paired box protein 6 (PAX6) gene led to the hypomethylation of PAX6 gene and increased PAX6 expression. Finally, the increased PAX6 via binding to the TPRC6 promoter contributes to the TRPC6 increase and mechanical allodynia following chemotherapeutics treatment. CONCLUSIONS: The TRPC6 upregulation through DNMT3b-mediated PAX6 gene hypomethylation participated in mechanical allodynia following application of different chemotherapeutic drugs.
Subject(s)
Antineoplastic Agents/pharmacology , DNA (Cytosine-5-)-Methyltransferases/drug effects , DNA Methylation/drug effects , Ganglia, Spinal/drug effects , Gene Expression/drug effects , Hyperalgesia/chemically induced , Neuralgia/chemically induced , PAX6 Transcription Factor/drug effects , TRPC Cation Channels/drug effects , Animals , Bortezomib/pharmacology , Disease Models, Animal , Hyperalgesia/drug therapy , Hyperalgesia/etiology , Male , Neuralgia/complications , Oxaliplatin/pharmacology , Paclitaxel/pharmacology , Rats , Rats, Sprague-Dawley , TRPC Cation Channels/antagonists & inhibitors , Up-Regulation/drug effects , DNA Methyltransferase 3BABSTRACT
PURPOSE: Intermittent hypoxia is a characteristic pathological change in obstructive sleep apnoea (OSA) that can initiate oxidative stress reaction and pro-inflammatory cytokine release. The purpose of this study was to assess the effect and protective mechanism of Astragaloside IV (AS-IV) in intermittent hypoxia-induced human lung epithelial Beas-2B cells. METHODS: Human lung epithelial Beas-2B cells were exposed to intermittent hypoxia or normoxia in the absence or presence of AS-IV. MTT assay was performed to determine the cell viability. The levels of reactive oxygen species (ROS), lactate dehydrogenase (LDH), malonaldehyde (MDA), and superoxide dismutase (SOD) were measured to evaluate oxidative stress. The levels of cytokines interleukin (IL)-8, IL-1ß, and IL-6 were evaluated by enzyme-linked immunosorbent assay and real-time PCR. The expression of Toll-like receptor 4 (TLR4), mitogen-activated protein kinase (MAPK), and nuclear transcription factor-kappa B (NF-κB) signalling pathways was analysed by western blot. RESULTS: The results showed that AS-IV significantly reduced the levels of ROS, LDH, MDA, IL-8, IL-1ß, and IL-6, and increased the level of SOD in intermittent hypoxia-induced Beas-2B cells. It also suppressed the phosphorylation of MAPKs, including P38, c-Jun N-terminal kinase and extracellular signal-regulated kinase, and inhibited the activation of the NF-κB signalling pathway by reducing the phosphorylation of IκBα and p65. CONCLUSIONS: AS-IV attenuates inflammation and oxidative stress by inhibiting TLR4-mediated MAPK/NF-κB signalling pathways in intermittent hypoxia-induced Beas-2B cells.
Subject(s)
Hypoxia/drug therapy , Inflammation/drug therapy , Lung/drug effects , MAP Kinase Signaling System/drug effects , Protein Serine-Threonine Kinases/drug effects , Respiratory Mucosa/drug effects , Saponins/pharmacology , Sleep Apnea, Obstructive/drug therapy , Triterpenes/pharmacology , Cells, Cultured , Humans , Hypoxia/etiology , Hypoxia/immunology , Hypoxia/metabolism , Inflammation/etiology , Inflammation/immunology , Inflammation/metabolism , Lung/cytology , Lung/immunology , Lung/metabolism , Protein Serine-Threonine Kinases/metabolism , Respiratory Mucosa/immunology , Respiratory Mucosa/metabolism , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/immunology , Sleep Apnea, Obstructive/metabolism , NF-kappaB-Inducing KinaseABSTRACT
In order to obtain a better fermentation parameter for the production of recombinant Ganoderma lucidum immunomodulatory protein (rFIP-glu), an engineered Pichia pastoris GS115 was investigated on the fermentation time, temperature, methanol concentration and initial pH of media, while immunomodulatory activities of the rFIP-glu was confirmed. L9(33) orthogonal experiment were firstly employed to optimize various fermentation parameters in the shake-flask level. The optimized fermentation parameters were subsequently verified in a 5 L fermenter. Biological activities including cell viability and tumor necrosis factor-alpha (TNF-α) mRNA of the rFIP-glu were evaluated on murine macrophage RAW264.7 cells. The results showed that the yield of rFIP-glu was up to 368.71 µg/ml in the shake-flask, and 613.47 µg/ml in the 5 L fermenter, when the Pichia pastoris was incubated in basic media with the methanol concentration 1.0% and initial pH 6.5, and with constant shaking at 280 rpm for 4 days at 26 °C. In vitro assays of biological activity indicated that rFIP-glu had significant toxicity against RAW264.7 cells, and possessed the ability to induce TNF-α mRNA expression in macrophage RAW264.7 cells. In conclusion, engineered P. pastoris showed a good fermentation property under the optimum fermentation parameters. It could be a candidate industrial strain for further study.
Subject(s)
Bioreactors , Fungal Proteins/biosynthesis , Pichia/metabolism , Recombinant Proteins/biosynthesis , Animals , Fermentation , Fungal Proteins/toxicity , Mice , RAW 264.7 Cells , Recombinant Proteins/toxicity , Reishi/chemistry , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Jinze Reservoir is the main drinking water source for southwest Shanghai. The water quality in the upstream Taipu River and reservoir have an important impact on the performance of the reservoir and the quality of the water supply. Conventional water parameters were analyzed using principal component analysis (PCA) to evaluate seasonal variations in water quality in the upper reaches of Jinze Reservoir. The parallel factor (PARAFAC) was also used to analyze water-soluble dissolved organic matter (FDOM) in the upstream waters and reservoir area. Furthermore, the relationships between water fluorescence intensity and conventional water quality indicators were analyzed using correlation analysis. The results show that water quality in the upper reaches of Jinze Reservoir is worst in the winter, and water quality gradually deteriorates in the outer sections of the reservoir due to external pollution inputs. Ecological purification within the reservoir area functions to improve water quality. The water body FDOM content is mainly composed of proteinoids and humus. Protein-like substances are the main components of this material, and each component exhibits clear spatial and temporal distribution characteristics. External pollution is the main factor affecting the total fluorescence intensity of the FDOM outside of the reservoir. In the reservoir, the ecological environment affects the total fluorescence intensity of FDOM. The total fluorescence intensity of FDOM showed an increasing downstream spatial trend, which was significantly correlated with NH4+-N, petroleum, TOC, chloride, and sulfate content in the water. By detecting the total fluorescence intensity of FDOM, the rapid analysis of water quality can be achieved to inform early warning.
ABSTRACT
Ganoderma have been regarded as a traditional source of natural bioactive compounds for centuries and have recently been exploited for potential components in the cosmetics industry. Besides Ganoderma polysaccharides and triterpenes, multiple proteins have been found in Ganoderma. With the in-depth study of these proteins, various pharmacological functions of Ganoderma have become important in the discovery and development of new products. In the review, we summarized and discussed the kinds and characteristics of Ganoderma proteins, especially on fungal immunomodulatory proteins (FIPs) which can be potentially developed into cosmeceuticals or nutricosmetics and are a suitable target for production using established biotechnological methods. Furthermore, we discuss their pharmacological activities of the proteins with a focus on their pharmacological functions related to cosmetics, such as antioxidant activity, inhibition of melanin, antibacterial activity, and regulation of inflammatory mediators. Numerous other questions also are addressed before the proteins can be widely accepted and used as cosmetic additives.
Subject(s)
Cosmetics/analysis , Fungal Proteins/chemistry , Ganoderma/chemistry , Animals , Humans , Mice , Polysaccharides/metabolism , Triterpenes/metabolismABSTRACT
Biofilm in the water distribution system is composed of various active microorganisms, microbial residues, and organic and inorganic impurities. The growth of pipeline biofilms causes several drinking water hygiene problems, such as the colonization of opportunistic pathogens, corrosion of pipelines, and deterioration of water quality. To investigate the biofilm formation process and the distribution characteristics of live microorganisms attached to drinking water pipe walls, heterotrophic plate count (HPC), flow cytometry (FCM), and high-throughput 16S rRNA sequencing were analyzed to examine the growth characteristics and diversity of active microorganisms on the wall of three typical building water supply pipeline materials:polyvinyl chloride (PVC), polypropylene random (PPR), and stainless steel (STS). The results showed that after 73 d, the biomass on the PVC pipe wall was firstly up to peak. The relationships between the maximum biomass and mature biofilm biomass per unit area among the three pipelines were both PVC > PPR > STS. Regarding the composition and structure of the biofilm active bacterial community on the three different pipelines, the predominant phylum on PVC was Nitrospirae, while Verrucomicrobia was predominant on PPR and STS. The species richness and diversity of biofilm on STS were smallest, and thus the community structure was the simplest. Compared to STS, there were more Cyanobacteria and Actinomycetes on PVC and PPR-hence, odor is more likely to be an issue. The results demonstrated that pipe material can affect the community structure of the attached biofilm.
Subject(s)
Bacteria/growth & development , Biofilms/growth & development , Water Microbiology , Water Supply , Drinking Water , Polypropylenes , Polyvinyl Chloride , RNA, Ribosomal, 16S/genetics , Stainless Steel , Water QualityABSTRACT
Ischemia-reperfusion (I/R)-induced lung injury undermines lung transplantation (LTx) outcomes by predisposing lung grafts to primary graft dysfunction (PGD). Necrosis is a feature of I/R lung injury. However, regulated necrosis (RN) with specific signaling pathways has not been explored in an LTx setting. In this study, we investigated the role of RN in I/R-induced lung injury. To study I/R-induced cell death, we simulated an LTx procedure using our cell culture model with human lung epithelial (BEAS-2B) cells. After 18 h of cold ischemic time (CIT) followed by reperfusion, caspase-independent cell death, mitochondrial reactive oxygen species production, and mitochondrial membrane permeability were significantly increased. N-acetyl-Leu-Leu-norleucinal (ALLN) (calpain inhibitor) or necrostatin-1 (Nec-1) [receptor interacting serine/threonine kinase 1 (RIPK1) inhibitor] reduced these changes. ALLN altered RIPK1/RIPK3 expression and mixed lineage kinase domain-like (MLKL) phosphorylation, whereas Nec-1 did not change calpain/calpastatin expression. Furthermore, signal transducer and activator of transcription 3 (STAT3) was demonstrated to be downstream of calpain and regulate RIPK3 expression and MLKL phosphorylation during I/R. This calpain-STAT3-RIPK axis induces endoplasmic reticulum stress and mitochondrial calcium dysregulation. LTx patients' samples demonstrate that RIPK1, MLKL, and STAT3 mRNA expression increased from CIT to reperfusion. Moreover, the expressions of the key proteins are higher in PGD samples than in non-PGD samples. Cell death associated with prolonged lung preservation is mediated by the calpain-STAT3-RIPK axis. Inhibition of RIPK and/or calpain pathways could be an effective therapy in LTx.