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In recent years, there has been increasing interest in exploring the potential therapeutic advantages of Citrullus mucosospermus extracts (CME) for nonalcoholic steatohepatitis (NASH). In this study, we investigated the therapeutic effects of CME on NASH using a mice model. High-performance liquid chromatography (HPLC) was employed to identify cucurbitacin E and cucurbitacin E-2-O-glucoside from the CME. Although CME did not significantly alter the serum lipid levels in methionine- and choline-deficient (MCD) mice, it demonstrated a protective effect against MCD diet-induced liver damage. CME reduced histological markers, reduced alanine transaminase (ALT) and aspartame transaminase (AST) levels, and modulated key NASH-related genes, including C/EBPα, PPARγ, Fas, and aP2. In addition, CME was found to restore hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) activity, both crucial for fat catabolism, and reduced the levels of pro-inflammatory cytokines. Furthermore, CME demonstrated the potential to mitigate oxidative stress by maintaining or enhancing the activation and expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and superoxide dismutase (SOD), both pivotal players in antioxidant defense mechanisms. These findings underscore the promising therapeutic potential of CME in ameliorating liver damage, inflammation, and oxidative stress associated with NASH.
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This study aimed to investigate the therapeutic potential of Citrullus mucosospermus extract (CME) in counteracting adipogenesis and its associated metabolic disturbances in murine models. In vitro experiments utilizing 3T3-L1 preadipocytes revealed that CME potently inhibited adipocyte differentiation, as evidenced by a dose-dependent reduction in lipid droplet formation. Remarkably, CME also attenuated glucose uptake and intracellular triglyceride accumulation in fully differentiated adipocytes, suggesting its ability to modulate metabolic pathways in mature adipose cells. Translating these findings to an in vivo setting, we evaluated the effects of CME in C57BL/6N mice fed a high-fat diet (HFD) for 10 weeks. CME administration, concomitantly with the HFD, resulted in a significant attenuation of body weight gain compared to the HFD control group. Furthermore, CME treatment led to substantial reductions in liver weight, total fat mass, and deposits of visceral and retroperitoneal adipose tissue, underscoring its targeted impact on adipose expansion. Histological analyses revealed the remarkable effects of CME on hepatic steatosis. While the HFD group exhibited severe lipid accumulation within liver lobules, CME dose-dependently mitigated this pathology, with the highest dose virtually abolishing hepatic fat deposition. An examination of adipose tissue revealed a progressive reduction in adipocyte hypertrophy upon CME treatment, culminating in a near-normalization of adipocyte morphology at the highest dose. Notably, CME exhibited potent anti-inflammatory properties, significantly attenuating the upregulation of pro-inflammatory cytokines' mRNA levels (TNF-α, IL-1ß and IL-6) in the livers of HFD-fed mice. This suggests a potential mechanism through which CME may exert protective effects against inflammation associated with obesity and fatty liver disease.
Subject(s)
3T3-L1 Cells , Adipogenesis , Diet, High-Fat , Mice, Inbred C57BL , Plant Extracts , Weight Gain , Animals , Diet, High-Fat/adverse effects , Plant Extracts/pharmacology , Mice , Weight Gain/drug effects , Male , Adipogenesis/drug effects , Adipocytes/drug effects , Obesity , Liver/drug effects , Liver/metabolism , Adipose Tissue/drug effects , Adipose Tissue/metabolismABSTRACT
INTRODUCTION: The Holdaway difference represents the relationship of the NB line to the mandibular incisor (NB-L1) and the bony pogonion (NB-Pog). This study aimed to evaluate treatment changes of NB-L1, NB-Pog, and the Holdaway difference in patients with skeletal Class I and II relationships with 3 different skeletal divergencies. METHODS: This retrospective study was the second part of treatment outcome assessments of 135 white adolescent patients (females, n = 69; males, n = 66; mean age, 12.8 ± 1.4 years pretreatment and 15.0 ± 1.4 years posttreatment). The NB-L1, NB-Pog, and Holdaway differences (NB-L1 - NB-Pog) were measured. The mixed-model analysis of variance was used to assess within- and between-subject effects responding to horizontal and vertical skeletal discrepancies. RESULTS: For the group with favorable profile changes, the means of the Holdaway difference were maintained in the hypodivergent and normodivergent subgroups and reduced in the hyperdivergent subgroups for patients with skeletal Class I and II relationships. The means of NB-L1 and Holdaway difference were significantly larger in the skeletal Class II group and became greater as skeletal vertical divergencies increased. The NB-Pog means were significantly different only between the hypodivergent and hyperdivergent subgroups. CONCLUSIONS: Based on the findings of this study, the Holdaway difference should be adjusted to individualize the incisor positions, considering not only the anteroposterior but also the vertical skeletal relationships of the patients.
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Malocclusion, Angle Class II , Mandible , Adolescent , Child , Female , Humans , Male , Cephalometry , Malocclusion, Angle Class II/therapy , Outcome Assessment, Health Care , Retrospective Studies , WhiteABSTRACT
This study investigated the role of phospholipase D (PLD) in retinal ischemia-reperfusion (I/R) injury using an oxygen-glucose deprivation/reperfusion (OGD/R) model commonly used in retinal I/R injury research. To create an in vitro cellular I/R model, pharmacological inhibitors and small interfering RNA (siRNA) were used to target PLD1 and PLD2 in retinal pigment epithelial (RPE) cells. Treatment with PLD inhibitors and siRNA reduced reactive oxygen species (ROS) and malondialdehyde (MDA) induced by OGD/R in RPE cells and increased the levels of superoxide dismutase (SOD) and glutathione (GSH), indicating a reduction in oxidative damage and improvement in the antioxidant system. Next, we showed that inhibiting PLD1 or PLD2 reduced intracellular iron levels and lipid peroxidation, which are critical factors in ferroptosis. Additionally, PLD1 and PLD2 modulated the expression of proteins involved in the regulation of ferroptosis, including GPX4, SLC7A11, FTH1, and ACSL4. We also investigated the roles of PLD1 and PLD2 in preventing pyroptosis, another form of programmed cell death associated with inflammation. Our study found that OGD/R significantly increased the production of pro-inflammatory cytokines and activated caspase-1, NLRP3, ASC, cleaved-caspase 1 (C-caspase-1), and GSDMD-N in RPE cells, indicating pyroptosis induction. However, PLD1 and PLD2 inhibition or knockdown significantly inhibited the production of pro-inflammatory cytokines and activation of the NLRP3 inflammasome, Taken together, our findings support the hypothesis that the PLD signaling pathway plays a key role in OGD/R-induced ferroptosis and pyroptosis induction and may be a potential therapeutic target for preventing or treating retinal dysfunction and degeneration.
Subject(s)
Ferroptosis , Reperfusion Injury , Humans , Pyroptosis , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Retinal Pigment Epithelium/metabolism , RNA, Small Interfering/metabolism , Cytokines/metabolism , Caspases/metabolism , Reperfusion Injury/metabolism , Reperfusion Injury/prevention & controlABSTRACT
This study investigated the anti-obesity effects of Cucumis melo var. gaettongchamoe (CG) in mice fed a high-fat diet (HFD). The mice received CG water extract (CGWE) treatment for 8 weeks, and changes in body weight and serum lipid levels were analyzed. The HFD + vehicle group showed a significant increase in body weight compared to the control group, while the HFD + CGWE and HFD + positive (orlistat) groups exhibited reduced body weight. Lipid profile analysis revealed lower levels of total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein cholesterol in the HFD + CGWE group compared to the HFD + vehicle group. The HFD + vehicle group had increased abdominal fat weight and fat content, whereas both HFD + CGWE groups showed significant reductions in abdominal fat content and adipocyte size. Additionally, CGWE administration downregulated mRNA expression of key proteins involved in neutral lipid metabolism. CGWE also promoted hepatic lipolysis, reducing lipid droplet accumulation in hepatic tissue and altering neutral lipid metabolism protein expression. Furthermore, CGWE treatment reduced inflammatory mediators and suppressed the activation of the mitogen-activated protein kinase pathway in hepatic tissue. In conclusion, CGWE shows promise as a therapeutic intervention for obesity and associated metabolic dysregulation, including alterations in body weight, serum lipid profiles, adipose tissue accumulation, hepatic lipolysis, and the inflammatory response. CGWE may serve as a potential natural anti-obesity agent.
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Adiposity , Cucumis melo , Animals , Mice , Mice, Obese , Diet, High-Fat/adverse effects , Plant Extracts/therapeutic use , Obesity/drug therapy , Obesity/etiology , Weight Gain , Liver/metabolism , Body Weight , Lipid Metabolism , Triglycerides , Cholesterol , Mice, Inbred C57BLABSTRACT
INTRODUCTION: This study investigated the interrelationship between FMIA and soft-tissue profile changes in skeletal Class I and II white adolescents with 3 different vertical skeletal patterns. METHODS: Two hundred seventy cephalometric images were constructed from pretreatment and posttreatment cone-beam computed tomography images of 135 white adolescents (69 females and 66 males with a mean age of 12.8 ± 1.4 years pretreatment and 15.0 ± 1.4 years posttreatment). SNA, SNB, ANB, Frankfort Mandibular Angle [FMA], Incisor Mandibular Plane Angle [IMPA], Frankfort-Mandibular Incisor Angle [FMIA], and Z angle were measured. A mixed-model analysis of variance was performed for patients with an increased posttreatment Z angle to evaluate within-subject and between-subject effects of variables in relation to horizontal and vertical skeletal patterns. Post-hoc tests were conducted to identify statistical significance among the 3 different divergent subgroups. RESULTS: Patients with a skeletal Class I relationship had straighter facial profiles and a larger FMIA than patients with a skeletal Class II relationship before and after treatment. FMA, FMIA, IMPA, and Z angle treatment changes were similar between the skeletal Class I and II groups. The final FMIA means of the 3 divergent subgroups converged at 65° in the skeletal Class I group and 60° in the skeletal Class II group. The mandibular incisors were uprighted during treatment in the hyperdivergent patients whose Z angle values increased after treatment. CONCLUSION: Horizontal skeletal relationships seem more suitable for determining the desired FMIA in Tweed's total space analysis than vertical skeletal divergencies.
Subject(s)
Incisor , Malocclusion, Angle Class II , Adolescent , Child , Female , Humans , Male , Cephalometry , Incisor/diagnostic imaging , Incisor/anatomy & histology , Malocclusion, Angle Class II/diagnostic imaging , Malocclusion, Angle Class II/therapy , Mandible/diagnostic imaging , White PeopleABSTRACT
AIM: To evaluate the macular microcirculation changes in patients with diabetic retinopathy(DR)by optical coherence tomography angiography(OCTA), and correlate the risk factors that may affect the macular microcirculation, so as to provide a clinical basis for early screening, diagnosis and therapeutic intervention for DR.METHODS: Retrospective study. A total of 75 patients(75 eyes)with type 2 diabetes mellitus(DM)who came to the ophthalmology outpatient clinic and ward of Xi'an Central Hospital from May to October 2022 were collected, and the DM patients were further divided into non-DR(NDR)group, non-proliferative DR(NPDR)group and proliferative DR(PDR)group, with 28 eyes, 25 eyes and 22 eyes in each group respectively. OCTA was applied to perform a 3mm×3mm blood flow imaging scan of the macular retina to automatically obtain the vascular density(VD)of the superficial retinal macular foveal, the parafoveal(1~3mm), as well as the macular 3mm×3mm and the area of macular foveal avascular zone(FAZ). Furthermore, the alteration of these parameters in patients with different degrees of DR was analyzed.RESULTS: Compared with the NDR group, the VD of the 3mm×3mm superficial retinal capillary(SCP)in the macular region was decreased in both PDR and NPDR group(all P<0.017), and the VD of the parafoveal was decreased in each quadrant(P<0.017), with the most significant decrease in the PDR group. The FAZ area of patients in the PDR and NPDR groups was significantly larger than that in the NDR group(P<0.017). Age, homocysteine, best corrected visual acuity(LogMAR), axial length and glycosylated hemoglobin(HbA1c)of patients with DR were negatively correlated with VD in the macular foveal(P<0.05), while homocysteine, best corrected visual acuity(LogMAR), axial length, and the duration of diabetes were negatively correlated with VD in the macular 3mm×3mm(P<0.05). Triglycerides, best corrected visual acuity(LogMAR), and HbA1c were negatively correlated with VD in the parafoveal(P<0.05), while total cholesterol and central macular thickness had no significant correlation with VD(P>0.05).CONCLUSION: The microcirculation changes in the macular area of DR patients can be monitored by OCTA, and the systemic condition of DR patients is closely related to their macular microcirculation.
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OBJECTIVE To establish comprehensive quality evaluation method based on multi-index components combined with multivariate statistical analysis, and to comprehensively evaluate the quality of Periploca forrestii. METHODS Taking 11 batches of P. forrestii medicinal materials from different areas in Guizhou as samples, the contents of neochlorogenic acid, cryptochlorogenic acid, chlorogenic acid, procyanidin A2, isochlorogenic acid A and isochlorogenic acid C were determined by HPLC. Clustering heat map analysis, grey correlation analysis(GRA) and technique for order preference by similarity to ideal solution(TOPSIS) were used to evaluate the quality of P. forrestii. RESULTS The results of methodological investigation of content determination were in accordance with the relevant regulations, and the linear relationship and accuracy of each component were good in their respective sampling range. The contents of chlorogenic acid, cryptochlorogenic acid, neochlorogenic acid, procyanidin A2, isochlorogenic acid A and isochlorogenic acid C in 11 batches of samples were 3.650-7.302, 0.888-2.575, 1.371- 2.386, 0.947-1.469, 0.084-0.169 and 0.725-1.067 mg/g, respectively. The content of each component was significantly different, with the highest content of chlorogenic acid and the lowest content of isochlorogenic acid A. The comprehensive results of cluster heat map, GRA and TOPSIS analysis showed that the comprehensive quality of S5 and S10 was relatively good. CONCLUSIONS The established method is accurate, stable and simple. Combined with multivariate statistical analysis method, it can be used for quality evaluation of P. forrestii. The quality of samples from Jiuzhou Town and Caiguan Town of Xixiu District in Anshun City of Guizhou Province are relatively good among 11 different origin samples.
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AIM:From the perspective of regulating mitochondrial complex I activity by DJ-1 protein,this study aims to explore the mechanism of DJ-1-mediated resveratrol(RES)preconditioning in protecting against oxidative stress injury induced by myocardial ischemia-reperfusion(I/R)in rats.METHODS:After intramyocardial injection of lentivirus carrying DJ-1 shRNA(sh-DJ-1)or negative control(NC)shRNA,the myocardial I/R model was constructed by ligating the left anterior descending branch of the rat coronary artery.Sprague-Dawley(SD)rats were randomly divided in-to 6 groups:sham group,I/R group,RES+I/R group,NC+RES+I/R group,sh-DJ-1+RES+I/R group,and IACS-010759(mitochondrial complex I inhibitor)+RES+I/R group,with 10 rats in each group.The rats in RES treatment groups were given RES(20 mg/kg)via gavage for 7 d prior to the myocardial I/R modeling,once daily.Moreover,the rats in sham and I/R groups received an equivalent volume of normal saline via gavage.Myocardial infarction area and cardiac function were assessed by TTC staining and echocardiography,respectively.The MitoSOX fluorescent probe was used to detect levels of mitochondrial reactive oxygen species(ROS)in the myocardium.The levels of malondialdehyde(MDA),superoxide dis-mutase(SOD)and lactate dehydrogenase(LDH)in the serum were detected using kits.Western blot and co-immunopre-cipitation assays were used to observe the interaction between DJ-1 and the two subunits,ND-1 and NDUFA4,of the mito-chondrial complex I.RESULTS:Compared with I/R group,RES pretreatment significantly reduced the myocardial in-farction area,mitochondrial ROS levels,serum LDH activity,and serum MDA content(P<0.01).It also elevated left ventricular ejection fraction,left ventricular fractional shortening and serum SOD activity(P<0.01).Pretreatment with RES increased the expression and mitochondrial translocation of DJ-1(P<0.01),promoted the interaction between DJ-1 and ND-1/NDUFA4,which in turn protected the activity of mitochondrial complex I(P<0.01).However,when the ex-pression of DJ-1 was suppressed,the protective effects of RES against myocardial I/R injury were significantly inhibited compared with RES+I/R group(P<0.05 or P<0.01).CONCLUSION:Pretreatment with RES increases the expression and mitochondrial translocation of DJ-1,and facilitates the interaction of DJ-1 with ND1 and NDUFA4 subunits of mito-chondrial complex I,thus preserving the activity of mitochondrial complex I and attenuating myocardial I/R-induced oxida-tive stress damage.
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Conventional breeding of wild (Cucumis melo var. makuwa Makino (CM)) and cultivated (Cucumis melo var. reticulatus (CR)) melons is aimed at improving their biological traits. Here, we prepared a nontoxic, bioactive extract of vitalmelon (F1 hybrid) and evaluated its antiadipogenic and antiobesity effects in fully differentiated 3T3-L1 adipocytes and high-fat diet- (HFD-) induced obese C57BL/6 mice. In fully differentiated 3T3-L1 adipocytes, the vitalmelon extract reduced the DMI- (dexamethasone, 3-isobutyl-1-methylxanthine, and insulin-) induced increases in lipid droplet number and intracellular glucose and triglyceride levels. In addition, the extract inhibited 3T3-L1 preadipocyte differentiation by downregulating PPAR-γ and target genes LPL, CD36, HMGCR, and L-FABP. To investigate the inhibitory effects of the vitalmelon extract on lipid metabolism, we measured serum lipid, hormone, and cytokine concentrations; lipolytic activity; lipid accumulation; and adipogenesis in HFD-fed mice treated with the extract. The HFD+vitalmelon-fed mice showed lower blood cholesterol, free fatty acid, sugar, leptin, and insulin concentrations but higher blood adiponectin concentrations than the HFD-fed mice. Moreover, the HFD+vitalmelon-fed mice showed lower abdominal fat levels, smaller fat cells, lower weight, and fewer lipid droplets in the liver tissue than the HFD-fed mice. Therefore, in HFD-fed mice, vitalmelon regulated lipid metabolism through PPAR-γ, highlighting its potential as a promising antiobesity functional food.
Subject(s)
Adipogenesis , Anti-Obesity Agents , 1-Methyl-3-isobutylxanthine/pharmacology , 3T3-L1 Cells , Adiponectin/pharmacology , Animals , Anti-Obesity Agents/pharmacology , Cholesterol , Cytokines/pharmacology , Dexamethasone/pharmacology , Diet, High-Fat/adverse effects , Fatty Acids, Nonesterified , Fruit/metabolism , Glucose/pharmacology , Insulin , Leptin/pharmacology , Mice , Mice, Inbred C57BL , Obesity/metabolism , PPAR gamma/metabolism , Plant Extracts/pharmacology , Sugars , TriglyceridesABSTRACT
Skin cancer is the most common human malignancy worldwide and solar ultraviolet (UV) radiation is known to serve an important role in its pathogenesis. Natural candidate compounds with antioxidant, photoprotective and antimelanogenic effects were investigated against the background of skin photoprotective and antimelanogenic properties. Gomisin D, J and O are dibenzocyclooctadiene lignans present in Kadsura medicinal plants and possess several pharmacological activities. In this study, the functions and mechanisms underlying the effects of gomisin D, J and O in UVAand UVBirradiated keratinocytes and αmelanocyte stimulating hormone (αMSH)stimulated melanocytes were explored. Following UVA and UVB irradiation, keratinocytes were treated with gomisin D, J and O, and keratinocyte viability, lactate dehydrogenase (LDH) release, intracellular reactive oxygen species (ROS) production and apoptosis were examined. The results demonstrated that gomisin D and J improved keratinocyte viability and reduced LDH release under UVA and UVB irradiation. Intracellular ROS production induced by UVA and UVB irradiation was suppressed by gomisin D and J. In addition, Annexin V and TUNEL staining analysis indicated that gomisin D and J have significant antiapoptotic effects on UVAand UVBirradiated keratinocytes. After αMSH stimulation, melanocytes were treated with gomisin D, J and O, and the changes in melanocyte viability, intracellular melanin content, intracellular tyrosinase activity, and mechanisms underlying these changes were examined. Gomisin D markedly inhibited the αMSHinduced increase in intracellular melanin content and tyrosinase activity. Mechanistically, gomisin D reduced the protein and mRNA expression levels of microphthalmiaassociated transcription factor (MITF), tyrosinase, tyrosinaserelated protein (TRP)1 and TRP2 in αMSHstimulated melanocytes. In addition, gomisin D markedly downregulated αMSHinduced phosphorylation of protein kinase A and cAMP response element binding protein, which are known to be present upstream of the MITF, tyrosinase, TRP1 and TRP2 genes. Overall, gomisin D has photoprotective and antimelanogenic effects; these findings provide a basis for the production of potential brightening and photoprotective agents using natural compounds such as gomisin D.
Subject(s)
Dioxoles/pharmacology , Lignans/pharmacology , Polycyclic Compounds/pharmacology , Radiation-Protective Agents/pharmacology , Apoptosis/drug effects , Cell Survival/drug effects , China , HaCaT Cells , Humans , Kadsura/metabolism , Keratinocytes/metabolism , Melanins/metabolism , Melanocytes/metabolism , Plant Extracts/pharmacology , Reactive Oxygen Species/metabolism , Skin Neoplasms/metabolismABSTRACT
Kadsura coccinea (KC), a beneficial plant for human health, has been used for centuries in China, Thailand, and Korea in folk medicine and food. There is evidence supporting the biological effects of highly bioactive ingredients in KC such as lignans, triterpenoids, flavonoids, phenolic acids, steroids, and amino acids. In this study, we aimed to explore the effects, functions, and mechanisms of the extracts from KC root (KCR), stem (KCS), leaf (KCL), and fruit (KCF) in UVA and UVB-irradiated keratinocytes and α-melanocyte stimulating hormone (α-MSH)-stimulated melanocytes. First, the total polyphenol and flavonoid contents of KCR, KCS, KCL, and KCF and their radical scavenging activities were investigated. These parameters were found to be in the following order: KCL > KCR > KCS > KCF. UVA and UVB-irradiated keratinocytes were treated with KCR, KCS, KCL, and KCF, and keratinocyte viability, LDH release, intracellular ROS production, and apoptosis were examined. Our results demonstrated that KC extracts improved keratinocyte viability and reduced LDH release, intracellular ROS production, and apoptosis in the presence UVA and UVB irradiation. The overall photoprotective activity of the KC extracts was confirmed in the following order: KCL > KCR > KCS > KCF. Moreover, KC extracts significantly decreased the intracellular melanin content and tyrosinase activity in α-MSH-stimulated melanocytes. Mechanistically, KC extracts reduced the protein and mRNA expression levels of tyrosinase, tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2) in α-MSH-stimulated melanocytes. In addition, these extracts markedly downregulated myophthalmosis-related transcription factor expression and cAMP-related binding protein phosphorylation, which is upstream of the regulation of Tyrosinase, TRP-1, and TRP-2. The overall anti-melanogenic activity of the KC extracts was established in the following order. KCL > KCR > KCS > KCF. Overall, the KC extracts exert photoprotective and anti-melanogenic effects, providing a basis for developing potential skin-whitening and photoprotective agents.
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Monolayer transition metal dichalcogenides (TMDCs) with high crystalline quality are important channel materials for next-generation electronics. Researches on TMDCs have been accelerated by the development of chemical vapor deposition (CVD). However, antiparallel domains and twin grain boundaries (GBs) usually form in CVD synthesis due to the special threefold symmetry of TMDCs lattices. The existence of GBs severely reduces the electrical and photoelectrical properties of TMDCs, thus restricting their practical applications. Herein, the epitaxial growth of single crystal MoS2 (SC-MoS2 ) monolayer is reported on Au (111) film across a two-inch c-plane sapphire wafer by CVD. The MoS2 domains obtained on Au (111) film exhibit unidirectional alignment with zigzag edges parallel to the <110> direction of Au (111). Experimental results indicated that the unidirectional growth of MoS2 domains on Au (111) is a temperature-guided epitaxial growth mode. The high growth temperature provides enough energy for the rotation of the MoS2 seeds to find the most favorable orientation on Au (111) to achieve a unidirectional ratio of over 99%. Moreover, the unidirectional MoS2 domains seamlessly stitched into single crystal monolayer without GBs formation. The progress achieved in this work will promote the practical applications of TMDCs in microelectronics.
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Patients with hepatocellular carcinoma (HCC) suffer from few treatment options and poor survival rates. Here we report that endonuclease VIII-like protein 3 (NEIL3) is overexpressed in HCC and correlates with poor survival. All six HCC cell lines investigated were dependent on NEIL3 catalytic activity for survival and prevention of senescence, while NEIL3 was dispensable for nontransformed cells. NEIL3-depleted HCC cell lines accumulated oxidative DNA lesions specifically at telomeres, resulting in telomere dysfunctional foci and 53BP1 foci formation. Following oxidative DNA damage during mitosis, NEIL3 relocated to telomeres and recruited apurinic endonuclease 1 (APE1), indicating activation of base excision repair. META-FISH revealed that NEIL3, but not NEIL1 or NEIL2, is required to initiate APE1 and polymerase beta (POLB)-dependent base excision repair at oxidized telomeres. Repeated exposure of NEIL3-depleted cells to oxidizing damage induced chromatin bridges and damaged telomeres. These results demonstrate a novel function for NEIL3 in repair of oxidative DNA damage at telomeres in mitosis, which is important to prevent senescence of HCC cells. Furthermore, these data suggest that NEIL3 could be a target for therapeutic intervention for HCC. SIGNIFICANCE: This study describes compartmentalization of base excision repair during mitosis that is dependent on NEIL3, APE1, and POLB to repair oxidative damage accumulating at telomeres in hepatocellular carcinoma.
Subject(s)
Carcinoma, Hepatocellular/genetics , Liver Neoplasms/genetics , Mitosis/genetics , N-Glycosyl Hydrolases/metabolism , Telomere/metabolism , Humans , Oxidation-Reduction , TransfectionABSTRACT
A composite Mn-Cu-Ce tri-metal oxide supported on γ-Al2O3 (Mn-Cu-Ce/Al2O3) catalyst was prepared by an impregnation-calcination method and investigated in the catalytic ozonation treatment of real coal chemical wastewater (CCW). The catalyst was characterized by XRD, SEM, TEM, XRF, BET, and XPS techniques. The results showed that Mn, Cu, and Ce metal oxides were evenly distributed on the Al2O3 surface and the catalyst maintained a large surface area and a high pore volume compared with the pristine Al2O3. The synergy between Mn, Cu, and Ce oxides greatly enriched the catalytic active sites and enhanced the ozonation performance. The catalytic ozonation process with Mn-Cu-Ce/Al2O3 increased the removal rate of total organic carbon (TOC) by 31.6% compared with ozonation alone. The ketones, aromatic compounds, phenols, and nitrogen-containing heterocyclic compounds in CCW have been effectively degraded and mineralized by Mn-Cu-Ce/Al2O3 catalytic ozonation process, and its biodegradability has also been significantly improved. The experimental results of âOH scavengers revealed that the mechanism of Mn-Cu-Ce/Al2O3 catalytic ozonation was to promote the generation of âOH radicals. The catalytic activity of Mn-Cu-Ce/Al2O3 was only a slight decrease in six consecutive catalytic ozonation treatments, showing good stability. Therefore, Mn-Cu-Ce/Al2O3 can be used as a candidate catalyst for the advanced treatment of refractory organic wastewaters upon catalytic ozonation.
Subject(s)
Ozone , Water Pollutants, Chemical , Water Purification , Catalysis , Coal , Wastewater , Water Pollutants, Chemical/analysisABSTRACT
INTRODUCTION: The purpose of this cross-sectional retrospective study was to evaluate the patterns of pharyngeal airway volume change determined by cervical vertebral maturation (CVM) stage and compare it with that which was characterized by chronological age. Correlations between hyoid bone positions and airway volumes were also examined. METHODS: CVM staging was determined from cone-beam computed tomography scans of 420 white patients aged 9-15 years. Patients were stratified on the basis of sex and skeletal pattern to establish pharyngeal airway volume clusters for each CVM stage. The horizontal and vertical positions of hyoid bones were measured using Hyoidius and Sella. RESULTS: Males had larger pharyngeal airway volumes compared with females. In males, the largest increases in pharyngeal airway volumes occurred at an earlier CVM stage than females. No statistically significant differences in pharyngeal airway volumes were noted in subjects with skeletal Class I, II, and III malocclusion. The hyoid bone in males was more anteriorly and inferiorly positioned compared with females. The Class III group had a further forward position of the hyoid bone than the Class I and II groups. CONCLUSIONS: The patterns of pharyngeal airway change obtained using CVM staging did not correlate well with traditional maturational models for skeletal growth. It implies that chronologic age could be a relatively reliable indicator for the assessment of pharyngeal airway volumes in adolescents, as outlined in part 1 of the present study. Subjects with anteriorly and superiorly positioned hyoid bones exhibited smaller pharyngeal airway volumes, which highlights the role of soft tissue and its influence on airway patency.
Subject(s)
Hyoid Bone , Malocclusion, Angle Class III , Adolescent , Cephalometry , Child , Cone-Beam Computed Tomography , Cross-Sectional Studies , Female , Humans , Hyoid Bone/diagnostic imaging , Male , Mandible , Pharynx/diagnostic imaging , Retrospective StudiesABSTRACT
For many developed countries and regions, long-term care is becoming an important issue due to demographic changes and an increasing willingness and need of family members to let the elderly be taken care of by non-family members. Thus, effectively managing long-term care needs has become a major societal concern. In this paper, the public attitude towards long-term care and the satisfaction of long-term care services in Taiwan are examined. First, internal consistency reliability, exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) are applied to delete unimportant indicators. Second, structural equation modeling (SEM) is used to determine which indicators have a statistically significant influence on the public attitude toward long-term care and on the satisfaction of long-term care services. Third, artificial neural network (ANN) is applied to understand the relative importance of the indicators in influencing the public attitude and satisfaction of long-term care services. The contribution of this study is significant because some of the factors investigated in the study should be stressed by the government or institutions to provide more satisfactory services to the elderly and their families.
Subject(s)
Long-Term Care , Personal Satisfaction , Aged , Humans , Pilot Projects , Reproducibility of Results , TaiwanABSTRACT
OBJECTIVE: The objective of this study was to investigate the effects of maxillary central incisor (U1) inclination changes on alveolar bone and root length in the 20 Class II division 1 and 20 Class II division 2 (CII div1, CII div2) Caucasian adolescents treated without extraction. MATERIAL AND METHODS: Forty U1s from each group were assessed for root length and alveolar variables at the crestal, mid-root, and apical levels using sagittal sections obtained from CBCT images pre- and post-treatment. Mixed MANOVAs, Repeated measures MANOVAs, Pearson correlations, and regression analyses were performed. RESULTS: The facial bone height did not change significantly after an average of 15 degrees of proclination in the CII div2 group, whereas a statistically significant decrease in the palatal bone height was noted. However, in the CII div1 group, a statistically significant reduction in the facial and palatal bone height was observed with mild crown retroclination. Both groups had a significant decrease in total bone thickness at all levels, more decrease in the CII div2 group after treatment. No statistically significant difference in root length was observed between the groups during treatment. CONCLUSIONS: The findings support that the flaring of retroclined U1s as a process for normalizing U1 inclination did not harm the facial alveolar bone height in the CII div2 non-extraction treatment. Crown proclination itself was not correlated to the amount of root resorption in Class II div1&2 non-extraction treatments in adolescents.