Periodontal disease in patients with WHIM syndrome Brenchley, Laurie; McDermott, David H.; Gardner, Pamela J. ...
Journal of clinical periodontology,
April 2024, 2024-04-00, 20240401, Volume:
51, Issue:
4
Journal Article
Peer reviewed
Aim
WHIM (warts, hypogammaglobulinaemia, infections and myelokathexis) syndrome is a rare combined primary immunodeficiency disease caused by gain‐of‐function (GOF) mutations in the chemokine ...receptor CXCR4 and includes severe neutropenia as a common feature. Neutropenia is a known risk factor for periodontitis; however, a detailed periodontal evaluation of a WHIM syndrome cohort is lacking. This study aimed to establish the evidence base for the periodontal status of patients with WHIM syndrome.
Materials and Methods
Twenty‐two adult WHIM syndrome patients and 22 age‐ and gender‐matched healthy volunteers (HVs) were evaluated through a comprehensive medical and periodontal examination. A mouse model of WHIM syndrome was assessed for susceptibility to naturally progressing or inducible periodontitis.
Results
Fourteen patients with WHIM syndrome (63.6%) and one HV (4.5%) were diagnosed with Stage III/IV periodontitis. No WHIM patient presented with the early onset, dramatic clinical phenotypes typically associated with genetic forms of neutropenia. Age, but not the specific CXCR4 mutation or absolute neutrophil count, was associated with periodontitis severity in the WHIM cohort. Mice with a Cxcr4 GOF mutation did not exhibit increased alveolar bone loss in spontaneous or ligature‐induced periodontitis.
Conclusions
Overall, WHIM syndrome patients presented with an increased severity of periodontitis despite past and ongoing neutrophil mobilization treatments. GOF mutations in CXCR4 may be a risk factor for periodontitis in humans.
A new model of porous electrodes based on the Gibbs free energy is developed, in which lithium-ion (Li-ion) diffusion, diffusion-induced stress (DIS), Butler–Volmer (BV) reaction kinetics, and size ...polydispersity of electrode particles are considered. The influence of BV reaction kinetics and concentration-dependent exchange current density (ECD) on concentration profile and DIS evolution are numerically investigated. BV reaction kinetics leads to a decrease in Li-ion concentration and DIS. In addition, concentration-dependent ECD results in a decrease in Li-ion concentration and an increase in DIS. Size polydispersity of electrode particles significantly affects the concentration profile and DIS. Optimal macroscopic state of charge (SOC) should consider the influence of the microscopic SOC values and mass fractions of differently sized particles.
Many animal and plant pathogenic bacteria employ a type three secretion system (T3SS) to deliver type three effector proteins (T3Es) into host cells. Efficient secretion of many T3Es in the plant ...pathogen Xanthomonas campestris pv. campestris (Xcc) relies on the global chaperone HpaB. However, how the domain of HpaB itself affects effector translocation/secretion is poorly understood. Here, we used genetic and biochemical approaches to identify a novel domain at the C-terminal end of HpaB (amino acid residues 137-160) that contributes to virulence and hypersensitive response (HR). Both in vitro secretion assay and in planta translocation assay showed that the secretion and translocation of T3E proteins depend on the C-terminal region of HpaB. Deletion of the C-terminal region of HpaB did not affect binding to T3Es, self-association or interaction with T3SS components. However, the deletion of C-terminal region sharply reduced the mounts of free T3Es liberated from the complex of HpaB with the T3Es, a reaction catalyzed in an ATP-dependent manner by the T3SS-associated ATPase HrcN. Our findings demonstrate the C-terminal domain of HpaB contributes to disassembly of chaperone-effector complex and reveal a potential molecular mechanism underpinning the involvement of HpaB in secretion of T3Es in Xcc.
Among the regulatory policies, feed-in tariffs (FIT) and renewable portfolio standards (RPS) are the most popular to promote the development of renewable energy power industry. This paper uses system ...dynamics (SD) to establish models of long-term development of China's biomass power industry under FIT and RPS schemes, and provides a case study by using scenario analysis method. The model, on the one hand, not only clearly shows the complex logical relationship between the factors but also reveals the process of coordination between the two policy tools in the development of the industry. On the other hand, it provides a reference for scholars to study similar problems in different countries, thereby facilitating an understanding of biomass power's long-term sustainable development pattern under FIT and RPS schemes, and helping to provide references for policy-making institutions. The results show that in the perfect competitive market, the implementation of RPS can promote long-term and rapid development of China's biomass power industry given the constraints and actions of the mechanisms of RPS quota proportion, the TGC valid period, and fines, compared with FIT. At the end of the paper, policy implications are offered as references for the government.
•The models are based on the affect of policies for investors' enthusiasm.•System dynamics is used to analyze complex system of industry's development.•The models are suitable for similar problems in different countries.•The results reveal a long-term sustainable development of the industry.
Wound healing is a multi-phased pathophysiological process requiring chemoattractant receptor-dependent accumulation of myeloid cells in the lesion. Two G protein-coupled formylpeptide receptors Fpr1 ...and Fpr2 mediate rapid neutrophil infiltration in the liver of Listeria-infected mice by sensing pathogen-derived chemotactic ligands. These receptors also recognize host-derived chemotactic peptides in inflammation and injury. Here we report the capacity of Fprs to promote the healing of sterile skin wound in mice by initiating neutrophil infiltration. We found that in normal miceneutrophils rapidly infiltrated the dermis in the wound before the production of neutrophil-specific chemokines by the injured tissue. In contrast, rapid neutrophil infiltration was markedly reduced with delayed wound closure in mice deficient in both Fprs. In addition, we detected Fpr ligand activity that chemoattracted neutrophils into the wound tissue. Our study thus demonstrates that Fprs are critical for normal healing of the sterile skin wound by mediating the first wave of neutrophil infiltration.
An in vivo model of antiangiogenic therapy allowed us to identify genes upregulated by bevacizumab treatment, including Fatty Acid Binding Protein 3 (FABP3) and FABP7, both of which are involved in ...fatty acid uptake. In vitro, both were induced by hypoxia in a hypoxia-inducible factor-1α (HIF-1α)-dependent manner. There was a significant lipid droplet (LD) accumulation in hypoxia that was time and O2 concentration dependent. Knockdown of endogenous expression of FABP3, FABP7, or Adipophilin (an essential LD structural component) significantly impaired LD formation under hypoxia. We showed that LD accumulation is due to FABP3/7-dependent fatty acid uptake while de novo fatty acid synthesis is repressed in hypoxia. We also showed that ATP production occurs via β-oxidation or glycogen degradation in a cell-type-dependent manner in hypoxia-reoxygenation. Finally, inhibition of lipid storage reduced protection against reactive oxygen species toxicity, decreased the survival of cells subjected to hypoxia-reoxygenation in vitro, and strongly impaired tumorigenesis in vivo.
Combination therapy shows great promise in circumventing cisplatin resistance. We report herein the development of a novel nanoscale drug delivery system (nDDS) based nanotherapeutic that combines ...chemotherapy and photodynamic therapy (PDT) into one single platform to achieve synergistic anticancer capacity to conquer cisplatin resistance. Mesoporous silica nanoparticle (MSNs) was used as the drug delivery vector to conjugate cisplatin prodrug and to load photosensitizer chlorin e6 (Ce6) to afford the dual drug loaded delivery system MSNs/Ce6/Pt. The hybrid nanoparticles have an average diameter of about 100 nm and slightly positive surface charge of about 18.2 mV. The MSNs/Ce6/Pt nanoparticles can be efficiently internalized by cells through endocytosis, thereby achieving much higher cellular Pt uptake than cisplatin in cisplatin-resistant A549R lung cancer cells. After 660 nm light irradiation (10 mW/cm2), the cellular reactive oxygen species (ROS) level in MSNs/Ce6/Pt treated cells was elevated dramatically. As a result of these properties, MSNs/Ce6/Pt exhibited very potent anticancer activity against A549R cells, giving a half-maximal inhibitory concentration (IC50) value for the combination therapy of 0.53 μM, much lower than that of cisplatin (25.1 μM). This study suggests the great potential of nDDS-based nanotherapeutic for combined chemo-photodynamic therapy to circumvent cisplatin resistance.
This paper presents a new single ended fault location method for transmission line based on positive sequence superimposed network during auto-reclosing. The proposed method only requires local ...measurement data and can not only eliminate but also quantify the negative effects of fault resistance, fault distance, and unknown remote end source impedance, which are marked as the most challenging problems in single ended fault location algorithms. In this paper, by analyzing the operation of auto-reclosing, the transmission line model using positive sequence superimposed network during both fault time section and reclosing time section has been developed to establish the system equations regarding fault position and local measurement data of each discrete time section. In order to retrieve converged and accurate fault location from resulting nonlinear equations, the trust-region reflective algorithm is applied in this paper. Various case studies and evaluations based on EMTP/ATP and RTDS simulations have been carried out to illustrate the effectiveness of the proposed method. The proposed new fault location method is also potentially economical as it can be relatively straightforward to implement in the standard protection hardware platform.
The influence of extrusion conditions (temperature ranging from 170 to 220 °C, loads varying from 1.2 to 12.5 kg) and high-density polyethylene (HDPE) content on swelling behavior of polyoxymethylene ...(POM)/ethylene-vinyl acetate copolymer (EVA)/HDPE blend melts was examined. It was found the melt die-swell ratio of the blends decreased approximately linearly with rise in temperature, while it increased as a quadratic function with increasing shear rate or shear stress. The melt die-swell ratio increased with increasing HDPE weight fraction under constant test temperature, and the effect of temperature on the sensitivity of the melt die-swell ratio to the HDPE weight fraction was insignificant, while the effect of load on the melt die-swell ratio was significant. The correlation between the melt die-swell ratio of the blends and the HDPE weight fraction followed a quadratic relation. The melt extrudate swell behavior mechanisms of the blends during the die extrusion flow are discussed.
•The melt extrudate swell behavior mechanisms of the POM/EVA/HDPE blends were explained.•The factors affecting the melt extrudate swell behavior of the blends were deeply investigated.•The findings should be beneficial for development and processing of the POM blends.
Hypoxia in cancers results in the upregulation of hypoxia inducible factor 1 (HIF-1) and a microRNA, hsa-miR-210 (miR-210) which is associated with a poor prognosis.
In human cancer cell lines and ...tumours, we found that miR-210 targets the mitochondrial iron sulfur scaffold protein ISCU, required for assembly of iron-sulfur clusters, cofactors for key enzymes involved in the Krebs cycle, electron transport, and iron metabolism. Down regulation of ISCU was the major cause of induction of reactive oxygen species (ROS) in hypoxia. ISCU suppression reduced mitochondrial complex 1 activity and aconitase activity, caused a shift to glycolysis in normoxia and enhanced cell survival. Cancers with low ISCU had a worse prognosis.
Induction of these major hallmarks of cancer show that a single microRNA, miR-210, mediates a new mechanism of adaptation to hypoxia, by regulating mitochondrial function via iron-sulfur cluster metabolism and free radical generation.
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