ABSTRACT
Periodontitis, the second most common oral disease, is primarily initiated by inflammatory responses and osteoclast differentiation, in which the MAPK signaling pathway and mitochondrial function play important roles. 3-methyl-1H-indol-1-yl dimethylcarbamodithioate (3o), a hybrid of indole and dithiocarbamate, was first synthesized by our group. It has shown anti-inflammatory activity against lipopolysaccharide-induced acute lung injury. However, it is not known if 3o can exert effects in periodontitis. In vitro study: LPS-induced macrophage inflammation initiation and a receptor activator of nuclear factor κB ligand-stimulated osteoclast differentiation model were established. Cell viability, inflammatory cytokines, osteoclast differentiation, the MAPK signaling pathway, and mitochondrial function before and after treatment with 3o were investigated. In vivo study: Alveolar bone resorption, inflammatory cytokine expression, osteoclast differentiation, and the underlying mechanisms were assessed in mice with periodontitis. Inflammatory cytokine expression and osteoclast differentiation appeared downregulated after 3o treatment. 3o inhibited the MAPK signaling pathway and restored mitochondrial function, including mitochondrial reactive oxygen species, mitochondrial membrane potential, and ATP production. Meanwhile, 3o reduced inflammation activation and bone resorption in mice with periodontitis, reflected by the decreased expression of inflammatory cytokines and osteoclasts, implying that 3o inhibited the MAPK signaling pathway and the mitochondrial oxidative DNA damage marker 8-OHdG. These results highlight the protective role of 3o in periodontitis in mice and reveal an important strategy for preventing periodontitis.
Subject(s)
Indoles , MAP Kinase Signaling System , Mitochondria , Osteoclasts , Periodontitis , Animals , Mitochondria/drug effects , Periodontitis/drug therapy , Mice , MAP Kinase Signaling System/drug effects , Osteoclasts/drug effects , Indoles/pharmacology , Indoles/therapeutic use , Cell Differentiation/drug effects , Cytokines/metabolism , Reactive Oxygen Species/metabolism , Male , Membrane Potential, Mitochondrial/drug effects , Lipopolysaccharides/pharmacology , Alveolar Bone Loss/drug therapy , Mice, Inbred C57BL , RAW 264.7 CellsABSTRACT
Senegalese sole, Solea senegalensis, is a flatfish of high commercial value in the world. It has been identified as an interesting and promising species for marine commercial aquaculture diversification in Europe for at least four decades and was introduced to China in 2003. Early ontogenesis from embryo to juvenile stages in S. senegalensis was analysed under controlled laboratory conditions to provide morphological information for aquaculture. From 0 to 59 days post hatching (dph), 10-20 larvae were sampled and measured each day (0-17 dph) or every 2-6 days (17-59 dph). Morphological characteristics from the egg to the juvenile stage were described. The eggs were separate and spherical with multiple oil globules. After 3 dph, the yolk sac was completely absorbed, mouth and anus were open, a swim bladder appeared, and larvae began feeding on rotifers (Brachionus plicatilis). The larvae began metamorphosis as the notochord flexed upward and the left eye migrated upward after 10 dph. The left eye migrated to the dorsal midline at 15 dph. At 19 dph, the left eye was translocated to the right-ocular side, and the juveniles adopted a benthic lifestyle. The swim bladder degenerated, and the juveniles completed metamorphosis at 23 dph. The growth patterns of some parameters (TL, SL, BH, BW) during larval and juvenile development stages were identified. The inflection points, which are slopes of growth changes, were calculated in growth curves. Three inflection points occurring in the growth curves of larvae and juveniles were found to be associated with metamorphosis, weaning, and transitions in feeding habits. The basic information of embryo development and ontogenesis in this study represents a valuable contribution to the S. senegalensis industry, especially in artificial breeding and rearing techniques.
Subject(s)
Flatfishes , Larva , Animals , Flatfishes/embryology , Flatfishes/growth & development , Larva/growth & development , Embryo, Nonmammalian , Aquaculture , Metamorphosis, Biological , Embryonic DevelopmentABSTRACT
OBJECTIVES: To verify the clinical significance of the best puncture-side bone cement/vertebral volume ratio (PSBCV/VV%) and bone cement leakage in paravertebral veins during vertebroplasty. METHODS: This was a retrospective analysis of a total of 210 patients from September 2021 to December 2022, who were divided into an observation group (110 patients) and a control group (100 patients). In the observation group, patients' preoperative computed tomography (CT) data were imported into Mimics software, and the VV was calculated using the three-dimensional (3D) reconstruction function. Then, based on the best PSBCV/VV% of 13.68% determined in a previous study, the optimal PSBCV to be injected during vertebroplasty was calculated. In the control group, vertebroplasty was performed directly using the conventional method. The incidence of cement leakage into paravertebral veins was observed postoperatively in both groups. RESULTS: There were no statistically significant differences (P > 0.05) in the evaluated indicators between the two groups pre- or postoperatively, including the anterior vertebral margin height, mid-vertebral height, injured vertebral Cobb angle, visual analogue scale (VAS) score, and Oswestry Disability Index (ODI). Intragroup comparisons showed improvements in the anterior vertebral height, mid-vertebral height, injured vertebral Cobb angle, VAS score, and ODI after surgery compared with before surgery (P < 0.05). In the observation group, there were 3 cases of cement leakage into the paravertebral veins, for a leakage rate of 2.7%. In the control group, there were 11 cases of cement leakage into the paravertebral veins, for a leakage rate of 11%. The difference in the leakage rate between the two groups was statistically significant (P = 0.016). CONCLUSION: In vertebroplasty, preoperative VV calculations using Mimics software, combined with calculation of the PSBCV according to the best PSBCV/VV% (13.68%), can effectively prevent leakage of bone cement into paravertebral veins and further prevent serious life-threatening complications such as pulmonary embolism.
Subject(s)
Fractures, Compression , Kyphoplasty , Osteoporotic Fractures , Spinal Fractures , Vertebroplasty , Humans , Bone Cements/adverse effects , Retrospective Studies , Spinal Fractures/surgery , Osteoporotic Fractures/surgery , Fractures, Compression/surgery , Treatment Outcome , Vertebroplasty/adverse effects , Vertebroplasty/methods , PuncturesABSTRACT
AIM: To investigate the regulatory role of miR-155 and Kinesin Superfamily Proteins-5C (KIF-5C) in the progression of pulpitis based on bioinformatic analysis. METHODOLOGY: Normal pulp tissues and pulpitis pulp tissues were collected and subjected to high-throughput sequencing and the differentially expressed miRNAs were determined. An in vitro and in vivo pulpitis model was established. HE, IHC staining and histological evaluation were used to verify the inflammatory state of human and mouse pulp tissues. The mRNA expression of IL-1ß and TGF-ß1 were determined by RT-qPCR and protein expression of IL-1α, IL-4, IL-8, IL-13, IFN-γ, IL-6, IL-10 and MCP-1 were determined by protein chip. The target genes of miR-155 were predicted by miRanda database and verified by Dual-luciferase reporter assay, RT-qPCR and western blotting. MiR-155 lentivirus were used to upregulate or downregulate miR-155 and the siRNA of KIF-5C was used to downregulate KIF-5C. The expression of miR-155 or KIF-5C was determined by RT-qPCR. All statistics were analysed using GraphPad prism 8.2. RESULTS: The high-throughput sequencing results showed that 6 miRNAs (miR-155, miR-21, miR-142, miR-223, miR-486, miR-675) were significantly upregulated in diseased human pulp tissues, and miR-155 was significantly elevated among the six miRNAs. RT-qPCR results demonstrated that miR-155 expression was upregulated in human pulpitic tissue, mice pulpitic tissue and LPS-HDPCs. IL-1ß was increased while TGF-ß1 was decreased in lenti-miR-155 transfected LPS-HDPCs. Analysis of protein chip results indicated that lenti-miR-155 transfected LPS-HDPCs produced higher levels of IL-8, IL-6, MCP-1. The opposite results were obtained when miR-155 was inhibited. Through miRanda database screen and Dual-luciferase reporter assay, the target gene (KIF-5C) of miR-155 was identified. In lenti-miR-155 transfected LPS-HDPCs, the expression of KIF-5C was downregulated. However, when shRNA-miR-155 was transfected to LPS-HDPCs, the opposite result was obtained. Silent RNA was used to knock down KIF-5C, the results showed that when both KIF-5C and miR-155 were knocked down simultaneously, the downregulated expression of inflammatory factors observed in LPS-HDPCs following miR-155 knockdown was rescued. CONCLUSION: MiR-155 plays an important role in promoting pulpitis through targeting KIF-5C and may serve as a potential therapeutic target.
Subject(s)
MicroRNAs , Pulpitis , Humans , Mice , Animals , Pulpitis/genetics , Pulpitis/metabolism , Transforming Growth Factor beta1/metabolism , Kinesins/genetics , Kinesins/metabolism , Lipopolysaccharides/pharmacology , Interleukin-6/metabolism , Interleukin-8/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Dental Pulp/metabolism , Luciferases/metabolismABSTRACT
OBJECTIVES: To explore the influencing factors of bone cement leakage in the paravertebral vein after vertebroplasty for the treatment of osteoporotic vertebral compression fractures (OVCFs) and to determine the correlation between the puncture-side bone cement/vertebral body volume ratio and bone cement leakage in the paravertebral vein. METHODS: This was a retrospective analysis of 495 patients (585 vertebral bodies) with OVCFs treated from August 2018 to May 2021 in our hospital. The patients' postoperative CT data were imported into Mimics software, and the three-dimensional(3D) reconstruction function was used to calculate the bone cement volume (BCV), puncture-side bone cement volume (PSBCV), and vertebral body volume (VBV); the bone cement/vertebral body volume ratio (BCV/VCV%) and puncture-side bone cement/vertebral body volume ratio (PSBCV/VCV%) were additionally calculated. Sex, Age, Body mass index(BMI), Bone density, BCV, PSBCV, VBV, BCV/VCV%, and PSBCV/VCV were compared between the leakage group and the non-leakage group. Logistic regression analysis was used to assess the correlations between the factors that statistically significantly differed between the two groups and the presence of leakage in the paravertebral veins. A receiver operating characteristic (ROC) curve was used to determine the diagnostic value of the PSBCV/VCV% and to obtain the optional cut-off value. RESULTS: A total of 102 males and 393 females with an average age of 72.89 (52 ~ 93) years were included in our study. There were 57 cases of cement leakage (59 vertebral bodies) in the paravertebral vein. There were 438 patients (526 vertebral bodies) without paravertebral cement leakage. Univariate analysis showed that the differences in sex, bone density, PSBCV, and PSBCV/VCV% between the two groups were statistically significant (P < 0.05). Logistic regression analysis showed that there were correlations between sex, bone density, and PSBCV/VCV% and the presence of paravertebral cement leakage (P < 0.05). The ROC curve showed that the area under the curve of the PSBCV/VCV% for the diagnosis of cement leakage in the paravertebral vein was greater than 0.65, and P < 0.05, indicating a diagnostic value. The best cut-off point for the diagnosis of paravertebral cement leakage with the PSBCV/VCV% was 13.68%, with a sensitivity of 84.7% and specificity of 37.8%. CONCLUSION: Sex, bone density, and PSBCV/VCV% are risk factors for cement leakage in the paravertebral veins after vertebroplasty for the treatment of OVCFs; the PSBCV/VCV% is strongly associated with paravertebral venous leakage, and the optimal PSBCV/VCV% is 13.68%. When the PSBCV/VCV% exceeds the optimal value, the risk of cement leakage in the paravertebral vein becomes significantly increased.
Subject(s)
Fractures, Compression , Osteoporotic Fractures , Spinal Fractures , Vertebroplasty , Aged , Bone Cements/adverse effects , Female , Fractures, Compression/complications , Fractures, Compression/diagnostic imaging , Fractures, Compression/surgery , Humans , Male , Osteoporotic Fractures/surgery , Punctures/adverse effects , Retrospective Studies , Spinal Fractures/chemically induced , Spinal Fractures/diagnostic imaging , Spinal Fractures/surgery , Treatment Outcome , Vertebral Body , Vertebroplasty/adverse effectsABSTRACT
BACKGROUND: Different bearings have been used in total hip arthroplasty (THA), but the long-term performance is still controversial. The purpose of this study was to investigate whether there are differences when comparing THAs with 5 different bearings at a long-term follow-up of more than 10 years. METHODS: From January 2010 to May 2012, 101 THA patients (134 hips) were divided into metal-on-metal group (MoM, 31 hips), metal-on-polyethylene group (MoP, 23 hips), ceramic-on-metal group (CoM, 21 hips), ceramic-on-ceramic group (CoC, 33 hips), and ceramic-on-polyethylene group (CoP, 26 hips). The mean follow-up period was 10.3 years. The Harris hip score (HSS), Western Ontario and McMaster Universities Osteoarthritis Index scores (WOMAC), range of motion (ROM), blood cell count, and liver-kidney function were measured. Serum and urine metal ion levels were measured using high-resolution inductively coupled plasma-mass spectrometry (ICP-MS) and a blood lymphocytes analysis was counted by flow cytometry. RESULTS: No difference was observed in the HSS, WOMAC, ROM, blood cell count, or liver-kidney function among any of the 5 groups. Metal ion levels were significantly elevated in metal-containing bearings. Flow cytometry showed that no differences were found. Revision was performed due to pseudotumor in 3 patients. The implant survival rate was 96.7% and 93.3% for the MoM and CoC groups, which was significantly lower compared with other groups. CONCLUSIONS: Metal ion levels were elevated significantly in metal-containing bearings, especially in MoM THA patients. The implant survival rate was significantly lower in CoC and MoM THAs, which was mainly due to pseudotumor formation. LEVEL OF EVIDENCE: Therapeutic Level II.
Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Arthroplasty, Replacement, Hip/methods , Ceramics , Follow-Up Studies , Humans , Lymphocytes , Metals , Polyethylene , Prosthesis Design , Prosthesis Failure , Reoperation , Retrospective StudiesABSTRACT
The presence of sequence divergence through adaptive mutations in the major capsid protein VP1, and also in VP0 (VP4 and VP2) and VP3, of foot-and-mouth disease virus (FMDV) is relevant to a broad range of viral characteristics. To explore the potential role of isolate-specific residues in the VP0 and VP3 coding regions of PanAsia-1 strains in genetic and phenotypic properties of FMDV, a series of recombinant full-length genomic clones were constructed using Cathay topotype infectious cDNA as the original backbone. The deleterious and compensatory effects of individual amino acid substitutions at positions 4008 and 3060 and in several different domains of VP2 illustrated that the chain-based spatial interaction patterns of VP1, VP2, and VP3 (VP1-3), as well as between the internal VP4 and the three external capsid proteins of FMDV, might contribute to the assembly of eventually viable viruses. The Y2079H site-directed mutants dramatically induced a decrease in plaque size on BHK-21 cells and viral pathogenicity in suckling mice. Remarkably, the 2079H-encoding viruses displayed a moderate increase in acid sensitivity correlated with NH4Cl resistance compared to the Y2079-encoding viruses. Interestingly, none of all the 16 rescued viruses were able to infect heparan sulfate-expressing CHO-K1 cells. However, viral infection in BHK-21 cells was facilitated by utilizing non-integrin-dependent, heparin-sensitive receptor(s) and replacements of four uncharged amino acids at position 3174 in VP3 of FMDV had no apparent influence on heparin affinity. These results provide particular insights into the correlation of evolutionary biology with genetic diversity in adapting populations of FMDV.IMPORTANCE The sequence variation within the capsid proteins occurs frequently in the infection of susceptible tissue cultures, reflecting the high levels of genetic diversity of FMDV. A systematic study for the functional significance of isolate-specific residues in VP0 and VP3 of FMDV PanAsia-1 strains suggested that the interaction of amino acid side chains between the N terminus of VP4 and several potential domains of VP1-3 had cascading effects on the viability and developmental characteristics of progeny viruses. Y2079H in VP0 of the indicated FMDVs could affect plaque size and pathogenicity, as well as acid sensitivity correlated with NH4Cl resistance, whereas there was no inevitable correlation in viral plaque and acid-sensitive phenotypes. The high affinity of non-integrin-dependent FMDVs for heparin might be explained by the differences in structures of heparan sulfate proteoglycans on the surfaces of different cell lines. These results may contribute to our understanding of the distinct phenotypic properties of FMDV in vitro and in vivo.
Subject(s)
Amino Acid Substitution/genetics , Capsid Proteins/genetics , Foot-and-Mouth Disease Virus/genetics , Foot-and-Mouth Disease/virology , Animals , CHO Cells , Cricetulus , Heparitin Sulfate/genetics , Mice , Open Reading Frames/genetics , Serogroup , Virion/geneticsABSTRACT
PURPOSE: The aim of this study was to demonstrate the surgical technique and clinical outcome of autologous neurosensory retinal patch transplantation for recurrent large macular hole (MH)-induced retinal detachment after failed surgery with internal limiting membrane (ILM) removal or transplantation. METHODS: We reviewed 5 patients with recurrent MH-induced retinal detachment after failed surgeries with ILM removal or transplantation who underwent vitrectomy combined with autologous neurosensory retinal patch transplantations and were followed up over 6 months. In the autologous neurosensory retinal patch transplantation procedure, a small piece of neurosensory retina was removed and transplanted inside the MH. The anatomic outcomes of MH-induced retinal detachment were evaluated by fundus examinations and optical coherence tomography. The pre-operative and postoperative best-corrected visual acuities (BCVAs) were compared and the MH closure rates were measured as the main outcomes. RESULTS: A total of 5 patients (3 men and 2 women; average age 35.4 ± 18.72 years) were included in our study. Complete MH sealing was achieved in 5 eyes after autologous neurosensory retinal patch transplantations, and no complications were observed. The mean BCVA was 2.38 ± 0.57 (range 1.6-3) before surgery, and 1.46 ± 0.51 (range 1-2) at 6 postoperative months. There was a significant difference in BCVA before versus after the surgery (p < 0.05, paired t test). CONCLUSIONS: Autologous neurosensory retinal patch transplantation is an effective addition to the surgical options for large MH-induced retinal detachment after failed surgery with ILM removal or transplantation.
Subject(s)
Retina/transplantation , Retinal Perforations/surgery , Adolescent , Adult , Child , Endotamponade , Female , Humans , Laser Coagulation , Male , Middle Aged , Retina/physiopathology , Retinal Detachment/etiology , Retinal Perforations/complications , Retinal Perforations/physiopathology , Retrospective Studies , Silicone Oils/administration & dosage , Tomography, Optical Coherence , Transplantation, Autologous , Visual Acuity/physiology , Vitrectomy/methods , Young AdultABSTRACT
Combination treatment through simultaneous delivery of DNA and anticancer drugs with nanoparticles has been demonstrated to be an elegant and efficient approach for cancer therapy. Herein, we employed a combination therapy for eliminating both the tumor cells and intratumoral neovascular network based on the nanoplatform we designed. Pigment epithelium-derived factor (PEDF) gene, a powerful antiangiogenic agent, and the clinically widely used chemotherapy agent paclitaxel (PTX) were simultaneously encapsulated in the same nanoparticle by a modified double-emulsion solvent evaporation method. The dual-drug-loaded nanoparticles (D/P-NPs) exhibited a uniform spherical morphology and released PTX and PEDF gene in a sustained manner. D/P-NPs showed an enhanced antitumor effect on C26 and A549 cells and a stronger inhibitory activity on proliferation of HUVECs. Moreover, D/P-NPs could dramatically elevate the PEDF expression levels in both C26 and A549 cells in comparison with PEDF gene loaded nanoparticles and significantly promote the cellular uptake of PTX. Additionally, microtubules were stabilized and G2/M phase arrest along with a higher subG1 cell population was induced by D/P-NPs in contrast to PTX or PTX loaded nanoparticles. Besides, D/P-NPs showed sustained release of PTX and PEDF gene in tumors as well as long-term gene expression. A significantly improved anticancer effect was also demonstrated in a C26 subcutaneous tumor model using this combinational therapy. D/P-NPs could sharply reduce the microvessel density and significantly promoted tumor cell apoptosis in vivo. More importantly, the in vivo distribution, serological and biochemical analysis, and H&E staining revealed that D/P-NPs had no obvious toxicity. Our study suggested that this novel polymeric nanomedicine had great potential for improving the therapeutic efficacy of combined gene/chemotherapy of cancer.
Subject(s)
Colonic Neoplasms/therapy , Drug Delivery Systems , Eye Proteins/genetics , Lung Neoplasms/therapy , Nanomedicine , Nanoparticles/administration & dosage , Nerve Growth Factors/genetics , Paclitaxel/pharmacology , Polymers/chemistry , Serpins/genetics , Animals , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Blotting, Western , Cell Cycle/drug effects , Cell Movement/drug effects , Cell Proliferation/drug effects , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Combined Modality Therapy , Fluorescent Antibody Technique , Humans , Immunoenzyme Techniques , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Mice , Mice, Inbred BALB C , Nanoparticles/chemistry , Polymers/administration & dosage , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, Cultured , Xenograft Model Antitumor AssaysABSTRACT
BACKGROUND: Toll-like receptor (TLR) agonists reportedly have potent antiviral and antitumor activities and may be a new kind of adjuvant for enhancing immune efficacy. Resiquimod (R848) is an imidazoquinoline compound with potent antiviral activity and functions through the TLR7/TLR8 MyD88-dependent signaling pathway. Polyinosinic-polycytidylic acid [poly(I:C)] is a synthetic analog of double-stranded RNA that induces the production of pro-inflammatory cytokines by the activation of NF-κB through TLR3. This study investigated the potential of R848 and poly(I:C) as an adjuvant 146S foot-and-mouth disease virus (FMDV) vaccine formulated with aluminum hydroxide (Al(OH)3). RESULTS: Antibody titers to FMDV and CD8+ T cells were markedly enhanced in mice immunized to 146S FMDV + Al(OH)3 + R848 + poly(I:C) compared with mice immunized to FMDV + ISA206. IFN-γ secretion substantially increased compared with IL-4 secretion by splenic T cells stimulated with FMDV antigens in vitro, suggesting that R848, poly(I:C), and with Al(OH)3 together biased the immune response toward a Th1-type direction. CONCLUSIONS: These results indicated that the R848 and poly(I:C) together with Al(OH)3 enhanced humoral and cellular immune responses to immunization with 146S FMDV antigens. Thus, this new vaccine formulation can be used for FMDV prevention.
Subject(s)
Adjuvants, Immunologic/pharmacology , Aluminum Hydroxide/pharmacology , Foot-and-Mouth Disease/prevention & control , Imidazoles/pharmacology , Poly I-C/pharmacology , Viral Vaccines/immunology , Adjuvants, Immunologic/administration & dosage , Aluminum Hydroxide/administration & dosage , Aluminum Hydroxide/chemistry , Animals , Antibodies, Viral/blood , Antibody Specificity , Female , Foot-and-Mouth Disease/immunology , Imidazoles/administration & dosage , Mice , Mice, Inbred BALB C , Poly I-C/administration & dosage , Spleen/cytology , Spleen/drug effects , T-Lymphocyte Subsets , Viral Vaccines/administration & dosageABSTRACT
Here, three novel cholesterol (Ch)/low molecular weight polyethylene glycol (PEG) conjugates, termed α, ω-cholesterol-functionalized PEG (Ch2-PEGn), were successfully synthesized using three kinds of PEG with different average molecular weight (PEG600, PEG1000 and PEG2000). The purpose of the study was to investigate the potential application of novel cationic liposomes (Ch2-PEGn-CLs) containing Ch2-PEGn in gene delivery. The introduction of Ch2-PEGn affected both the particle size and zeta potential of cationic liposomes. Ch2-PEG2000 effectively compressed liposomal particles and Ch2-PEG2000-CLs were of the smallest size. Ch2-PEG1000 and Ch2-PEG2000 significantly decreased zeta potentials of Ch2-PEGn-CLs, while Ch2-PEG600 did not alter the zeta potential due to the short PEG chain. Moreover, the in vitro gene transfection efficiencies mediated by different Ch2-PEGn-CLs also differed, in which Ch2-PEG600-CLs achieved the strongest GFP expression than Ch2-PEG1000-CLs and Ch2-PEG2000-CLs in SKOV-3 cells. The gene delivery efficacy of Ch2-PEGn-CLs was further examined by addition of a targeting moiety (folate ligand) in both folate-receptor (FR) overexpressing SKOV-3 cells and A549 cells with low expression of FR. For Ch2-PEG1000-CLs and Ch2-PEG2000-CLs, higher molar ratios of folate ligand resulted in enhanced transfection efficacies, but Ch2-PEG600-CLs had no similar in contrast. Additionally, MTT assay proved the reduced cytotoxicities of cationic liposomes after modification by Ch2-PEGn. These findings provide important insights into the effects of Ch2-PEGn on cationic liposomes for delivering genes, which would be beneficial for the development of Ch2-PEGn-CLs-based gene delivery system.
Subject(s)
Cations/chemistry , Cholesterol/analogs & derivatives , Gene Transfer Techniques , Liposomes/chemistry , Polyethylene Glycols/chemistry , Cell Death/drug effects , Cell Line, Tumor , Cholesterol/chemical synthesis , Cholesterol/chemistry , Cholesterol/toxicity , Fluorescence , Folate Receptor 1/metabolism , Folic Acid/chemistry , Humans , Ligands , Mass Spectrometry , Molecular Weight , Particle Size , Photoelectron Spectroscopy , Polyethylene Glycols/chemical synthesis , Polyethylene Glycols/toxicity , Proton Magnetic Resonance Spectroscopy , Static Electricity , Transfection , Transition TemperatureABSTRACT
OBJECTIVE: To investigate the relationship between the level of di-2-ethylhexyl phthalate (DEHP) and idiopathic oligoasthenospermia by measuring the content of DEHP in the semen samples of different subjects. METHODS: We obtained semen samples from 100 infertile men with idiopathic oligoasthenospermia, 50 working all the year round in the plastic greenhouse (group A) and the other 50 constantly dining from plastic meal boxes (group B). We also enrolled 50 normal male volunteers as controls (group C). We conducted semen analyses using a computer-assisted sperm analyzer, measured the DEHP concentration by reversed-phase high-pressure liquid chromatography, and subjected the data to statistic processing by t-test and correlation analysis. RESULTS: The mean concentrations of DEHP in the seminal plasma were (0.72 +/- 0.48), (0.71 +/- 0.49) and (0.21 +/- 0.18) mg/L in groups A, B and C, respectively, significantly higher in A and B than in C (both P < 0.05). The DEHP concentration was negatively correlated with sperm motility (P < 0.05). CONCLUSION: The DEHP level in the seminal plasma is higher in infertile men frequently exposed to plastic products than in normal males and excessive DEHP may be one of the important factors of idiopathic male infertility.
Subject(s)
Diethylhexyl Phthalate/adverse effects , Oligospermia/etiology , Adult , Case-Control Studies , Humans , Male , Plastics/adverse effects , Semen/chemistryABSTRACT
This study developed a novel organic-inorganic hybrid composite, shortly as GO-PEG-LDHs, by self-assembly of exfoliated Mg-Al layer double hydroxide (LDHs) on the polyethylene glycol (PEG) grafted graphene oxide (GO) to achieve the selective adsorption of hemoglobin (Hb). The prepared GO-PEG-LDHs has a hierarchical structure with a homogeneous loading of exfoliated LDHs nano-sheets on its surface. The adsorption test reveals that GO-PEG-LDHs exhibits an adsorption efficiency of 95.03% for Hb and 3.45% for bovine serum albumin (BSA). The adsorption of Hb follows the Langmuir model, with an ultrahigh adsorption capacity of 55248.6 mg/g, which is higher than any previously reported materials. Meanwhile, the adsorbed Hb can be efficiently recovered through elution with a 50 mM Tris-HCl buffer, with an elution efficiency of 80.77%. Circular dichroism (CD) spectra indicate no conformational change for Hb during the process of adsorption/desorption. Furthermore, the composite demonstrates the ability to selectively isolate Hb in the presence of interfering protein BSA, indicating its potential for practical applications.
Subject(s)
Graphite , Hemoglobins , Hydroxides , Polyethylene Glycols , Graphite/chemistry , Hemoglobins/chemistry , Adsorption , Polyethylene Glycols/chemistry , Hydroxides/chemistry , Cattle , Nanostructures/chemistry , Animals , Aluminum/chemistry , Serum Albumin, Bovine/chemistryABSTRACT
The appropriate degradation characteristics of polydioxanone (PDO) are necessary for the safety and effectiveness of stents. This study aimed to investigate the degradation of PDO weaving tracheal stents (PW stents)in vitroandin vivo. The degradation solution ofS. aureus(SAU),E. coli(ECO),P. aeruginosa(PAE), and control (N) were prepared, and the PW stents were immersed for 12 weeks. Then, the radial support force, weight retention, pH, molecular structure, thermal performance, and morphology were determined. Furthermore, the PW stents were implanted into the abdominal cavity of rabbits, and omentum was embedded. At feeding for 16 weeks, the mechanical properties, and morphology were measured. During the first 8 weeks, the radial support force in all groups was progressively decreased. At week 2, the decline rate of radial support force in the experimental groups was significantly faster compared to the N group, and the difference was narrowed thereafter. The infrared spectrum showed that during the whole degradation process, SAU, ECO and PAE solution did not lead to the formation of new functional groups in PW stents.In vitroscanning electron microscope observation showed that SAU and ECO were more likely to gather and multiply at the weaving points of the PW stents, forming colonies.In vivoexperiments showed that the degradation in the concavity of weaving points of PW stents was more rapid and severe. The radial support loss rate reached more than 70% at week 4, and the radial support force was no longer measurable after week 8. In omentum, multinuclear giant cells and foreign giant cells were found to infiltrate. PW stents have good biocompatibility. The degradation rate of PW stents in the aseptic conditionsin vivowas faster than in the bacteriological environmentin vitro.
Subject(s)
Materials Testing , Polydioxanone , Stents , Trachea , Animals , Polydioxanone/chemistry , Rabbits , Biocompatible Materials/chemistry , Staphylococcus aureus , Escherichia coli , Pseudomonas aeruginosa , Hydrogen-Ion Concentration , OmentumABSTRACT
OBJECTIVE: To construct a novel portable tooth sectioning guide to improve the accuracy of mandibular third molar extraction. METHODS: First, 72 samples of an identical 3D-printed double-rooted mandibular third molar were obtained and used in 36 mandibular models. Three different models were constructed (class B vertical, mesial, and horizontal impaction). Then, we made the tooth sectioning guides. mimicking clinical tooth sectioning conditions, two dental surgeons with different levels of experience used both the digital guided technique and the traditional empirical technique during surgery. Accuracy indicators, including apical deviation and angle deviation, were analyzed and compared on postoperative cone-beam computed tomographic scanning and via image reconstruction. Descriptive statistical analyses were performed. A p-value of 0.05 indicated statistically significant differences among the groups. RESULTS: Overall, the mean apical deviation of experienced/inexperienced operators using the conventional section technique was 1.120 mm (0.7 mm, 2.3 mm) and 1.54± 0.84 mm, respectively. Correspondingly, the mean apical deviation under the guided section technique was 0.28 mm (0.2 mm, 0.4 mm) and 0.32±0.16 mm, respectively. The mean angle deviations of experienced/inexperienced operators under the conventional section technique were 8.015° (3.5°, 10.5°) and 6.570° (5.5°, 14.9°). Correspondingly, the mean apical deviation using the guided section technique was 1.880° (0.4°, 2.9°) and 1.470° (0.7°, 3.1°), respectively. The conventional and guided techniques were significantly different (P < 0.001). CONCLUSIONS: In the digital guide technique, sectioning is more predictable and accurate, and the success of the operation is achievable with different proficiencies among dental surgeons. CLINICAL SIGNIFICANCE: This technique will not only reduce the difficulty of tooth extraction but also reduce the risk of damage to the surrounding soft and hard tissues, especially damage to the inferior alveolar nerve.
Subject(s)
Molar, Third , Tooth, Impacted , Humans , Molar, Third/surgery , Molar , Tooth, Impacted/surgery , Mandible/surgery , Tooth Extraction/adverse effects , Tooth Extraction/methodsABSTRACT
OBJECTIVES: The semiburied design of the traditional internal distractor has a relatively high risk of infection and aesthetic problems. To reduce these potential risks, a modified internal distractor with design of pre-embedding curvilinear rail, drive screw, and universal joint was invented. Its stress distribution characteristics and the effect on curvilinear distraction osteogenesis (DO) in vivo were further tested. MATERIALS AND METHODS: Finite element analysis (FEA) was performed on a model of the human mandible and distraction device to measure the stress distribution during curvilinear DO. Six beagles underwent curvilinear DO and consolidation using the new device. Radiological and histological examinations were performed on the new bone. RESULTS: On FEA, the stress was concentrated in the condyle (128.6 MPa) and curved guide rails (324.8 MPa). Four of the six animals completed the DO period and were consolidated for 12 weeks. Secondary infections were not observed. Radiography showed that a new fan-shaped bone-15.5 ± 5.5 mm in length and 4.6 ± 1.6 mm in height-was formed in the bone gap. Micro-computed tomography and histological examinations of specimens indicated that the structure of the new bone was similar to that of the normal bone. CONCLUSIONS: The modified internal curvilinear distraction device meets the mechanical strength requirement and achieve curvilinear DO in animal experiments.
Subject(s)
Animal Experimentation , Osteogenesis, Distraction , Dogs , Humans , Animals , Finite Element Analysis , X-Ray Microtomography , Mandible/surgery , Mandible/pathology , Osteogenesis, Distraction/methods , Bone ScrewsABSTRACT
Lignin is a complex biopolymer comprising phenolic monomers with different degrees of methoxylation and may potentially enhance the degradation of soil pollutants such as polycyclic aromatic hydrocarbons (PAHs) through co-metabolism. However, the contribution of lignin constituents, including phenolic and methoxy subunits, to PAH biodegradation remains unclear. Here, p-hydroxybenzoate (pHBA), vanillate and methanol were selected to simulate phenolic units and methoxy groups of lignin. Soil microcosms receiving these compounds were established to evaluate their regulation on the bacterial community and PAH co-metabolism. There were different effects of different components on the biodegradation of a four-ring PAH, benzo(a)anthracene (BaA), as characterized using an isotopic tracer. Only vanillate significantly stimulated BaA mineralization to CO2, with pHBA and methanol leading to no appreciable change in the allocation of BaA in soil compartments. The lignin constituents had differential impacts on the soil bacterial community, with substantial enrichment of methylotrophs occurring in methanol-supplemented microcosms. Both vanillate and pHBA selected several aromatic degraders. Vanillate caused additional enrichment of methylotrophs, suggesting structure-dependent stimulation of bacterial functional guilds by lignin monomers. Compared with its constituents, lignin produced more extensive responses in terms of bacterial diversity and composition and the fate of BaA. However, it was difficult to link BaA co-metabolism to any specific bacterial taxa in the presence of lignin or its subunits. The results indicate that the co-metabolism effects of lignin may not be directly associated with phenolic or methoxy metabolism but with its regulation of the soil microbiome.
Subject(s)
Polycyclic Aromatic Hydrocarbons , Soil Pollutants , Polycyclic Aromatic Hydrocarbons/analysis , Lignin/metabolism , Soil , Methanol , Agriculture , Biodegradation, Environmental , Soil Pollutants/analysis , Soil MicrobiologyABSTRACT
Zinc (Zn) and its alloys are used in bone-fixation devices as biodegradable bone-implant materials due to their good biosafety, biological function, biodegradability, and formability. Unfortunately, the clinical application of pure Zn is hindered by its insufficient mechanical properties and slow degradation rate. In this study, a Zn-5 wt.% lanthanum (Zn-5La) alloy with enhanced mechanical properties, suitable degradation rate, and cytocompatibility was developed through La alloying and hot extrusion. The hot-extruded (HE) Zn-5La alloy showed ultimate tensile strength of 286.3 MPa, tensile yield strength of 139.7 MPa, elongation of 35.7%, compressive yield strength of 262.7 MPa, and microhardness of 109.7 HV. The corrosion resistance of the HE Zn-5La in Hanks' and Dulbecco's modified Eagle medium (DMEM) solutions gradually increased with prolonged immersion time. Further, the HE Zn-5La exhibited an electrochemical corrosion rate of 36.7 µm/y in Hanks' solution and 11.4 µm/y in DMEM solution, and a degradation rate of 49.5 µm/y in Hanks' solution and 30.3 µm/y in DMEM solution, after 30 d of immersion. The corrosion resistance of both HE Zn and Zn-5La in DMEM solution was higher than in Hanks' solution. The 25% concentration extract of the HE Zn-5La showed a cell viability of 106.5%, indicating no cytotoxicity toward MG-63 cells. We recommend the HE Zn-5La alloy as a promising candidate material for biodegradable bone-implant applications. STATEMENT OF SIGNIFICANCE: This work reports the mechanical properties, corrosion and degradation behaviors, in vitro cytocompatibility and antibacterial ability of biodegradable Zn-5La alloy for bone-implant applications. Our findings demonstrate that the hot-extruded (HE) Zn-5La alloy showed an ultimate tensile strength of 286.3 MPa, a yield strength of 139.7 MPa, an elongation of 35.7%, compressive yield strength of 262.7 MPa, and microhardness of 109.7 HV. HE Zn-5La exhibited appropriate degradation rates in Hanks' and DMEM solutions. Furthermore, the HE Zn-5La alloy showed good cytocompatibility toward MG-63 and MC3T3-E1 cells and greater antibacterial ability against S. aureus.
Subject(s)
Alloys , Zinc , Materials Testing , Alloys/pharmacology , Alloys/chemistry , Corrosion , Zinc/pharmacology , Zinc/chemistry , Staphylococcus aureus , Absorbable Implants , Anti-Bacterial Agents , Biocompatible Materials/pharmacology , Biocompatible Materials/chemistryABSTRACT
Periodontitis is an oral microbiota-induced inflammatory disease, in which inflammation and oxidative stress play a critical role. Silibinin (SB), a Silybum marianum-derived compound, exhibits strong anti-inflammatory and antioxidative properties. We adopted a rat ligature-induced periodontitis model and a lipopolysaccharide- (LPS-) stimulated human periodontal ligament cells (hPDLCs) model to evaluate the protective effects of SB. In the in vivo model, SB reduced alveolar bone loss and apoptosis of PDLCs in the periodontal tissue. SB also maintained the expression of nuclear factor-E2-related factor 2 (Nrf2), a key regulator of cellular resistance to oxidative stress, and attenuated lipid, protein, and DNA oxidative damages in the periodontal lesion area. Meanwhile, in the in vitro model, SB administration reduced the production of intracellular reactive oxidative species (ROS). Furthermore, SB exerted a strong anti-inflammatory property in both in vivo and in vitro models by inhibiting the expression of inflammatory mediators including nuclear factor-κB (NF-κB) as well as nucleotide binding oligomerization domain- (NOD-) like receptor family pyrin domain-containing 3 (NLRP3) and downregulating the levels of proinflammatory cytokines. This study, for the first time, demonstrates that SB exhibits the anti-inflammatory and antioxidative properties against periodontitis by downregulating the expression of NF-κB and NLRP3 and upregulating Nrf2 expression, suggesting a promising potential clinical application of SB in periodontitis.
Subject(s)
NF-kappa B , Periodontitis , Rats , Humans , Animals , Silybin/pharmacology , Silybin/therapeutic use , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Down-Regulation , NF-E2-Related Factor 2/metabolism , Periodontitis/drug therapy , Periodontitis/pathology , Inflammation/pathology , Oxidative Stress , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Lipopolysaccharides/metabolismABSTRACT
Lignin enhanced biodegradation of polycyclic aromatic hydrocarbons (PAHs) in soil, but collaboration among soil microorganisms during this process remains poorly understood. Here we explored the relations between microbial communities and PAH transformation in soil microcosms amended with lignin. Mineralization of the four-ring benzo(a)anthracene (BaA), which was selected as a model, was determined by using an isotope-labeled tracer. The eukaryotic inhibitor cycloheximide and redox mediator ABTS were used to validate the fungal role, while microbial communities were monitored by amplicon sequencing. The results demonstrated that lignin significantly promoted BaA mineralization to CO2, which was inhibited and enhanced by cycloheximide and ABTS, respectively. Together with the increased abundance of Basidiomycota, these observations suggested an essential contribution of fungi to BaA biodegradation, which possibly through a ligninolytic enzyme-mediated pathway. The enrichment of Methylophilaceae and Sphingomonadaceae supported bacterial utilization of methyl and aryl groups derived from lignin, implicating cometabolic BaA degradation. Co-occurrence network analysis revealed increased interactions between fungi and bacteria, suggesting they played synergistic roles in the transformation of lignin and BaA. Collectively, these findings demonstrate the importance of synergy between fungi and bacteria in PAH transformation, and further suggest that the modulation of microbial interplay may ameliorate soil bioremediation with natural materials such as lignin.