ABSTRACT
Cotton plays a crucial role in the progress of the textile industry and the betterment of human life by providing natural fibers. In our study, we explored the genetic determinants of cotton architecture and fiber yield and quality by crossbreeding Gossypium hirsutum and Gossypium barbadense, creating a recombinant inbred line (RIL) population. Utilizing SNP markers, we constructed an extensive genetic map encompassing 7,730 markers over 2,784.2 cM. We appraised two architectural and seven fiber traits within six environments, identifying 58 QTLs, of which 49 demonstrated stability across these environments. These encompassed QTLs for traits such as lint percentage (LP), boll weight (BW), fiber strength (STRENGTH), seed index (SI), and micronaire (MIC), primarily located on chromosomes chr-A07, chr-D06, and chr-D07. Notably, chr-D07 houses a QTL region affecting SI, corroborated by multiple studies. Within this region, the genes BZIP043 and SEP2 were identified as pivotal, with SEP2 particularly showing augmented expression in developing ovules. These discoveries contribute significantly to marker-assisted selection, potentially elevating both the yield and quality of cotton fiber production. These findings provide valuable insights into marker-assisted breeding strategies, offering crucial information to enhance fiber yield and quality in cotton production.
Subject(s)
Chromosome Mapping , Cotton Fiber , Gossypium , Quantitative Trait Loci , Gossypium/genetics , Quantitative Trait Loci/genetics , Phenotype , Polymorphism, Single Nucleotide/genetics , Chromosomes, Plant/genetics , Plant Breeding/methods , Genetic MarkersABSTRACT
Influenza, a severe respiratory disease caused by the influenza virus, has long been a prominent threat to human health. An increasing number of studies have demonstrated that oral administration with probiotics may increase the immune response to lung infection via the gut-lung axis leading to the alleviation of the pulmonary disease. In this study, we evaluated the effects of oral administration of Pediococcus pentosaceus MIANGUAN2 (MIANGUAN2) on influenza infection in a mouse model. Our results showed that oral administration of MIANGUAN2 significantly improved weight loss, lung index, and lung pathology, and decreased lung viral load of influenza-infected mice. Additionally, MIANGUAN2-treated mice showed significantly lower levels of TNF-α, IL-1ß, IFN-γ, and IL-12p70 and higher production of IL-4 in the lung. In accordance with this, the transcriptome analysis of the lung indicated that MIANGUAN2-treated mice had reduced expression of inflammation markers, such as TNF, apoptosis, and the NF-Kappa B pathway. Furthermore, the administration of MIANGUAN2 restored the SCFAs profiles through regulating the gut microbiota. SCFA-producing bacteria, such as p_Firmicutes, f_Lachnospiraceae, and f_Ruminococcaceae, were enriched in the MIANGUAN2-treated group compared with PBS-treated group. Consistently, the concentrations of SCFAs in the MIANGUAN2 group were significantly higher than those in the PBS-treated group. In addition, the concentrations of SCFAs were positively correlated with SCFA-producing bacteria, such as Ruminococcus, while being negatively correlated with the virial titers and proinflammatory cytokines. In conclusion, this animal study suggests that Pediococcus pentosaceus MIANGUAN2 may alleviate the influenza infection by altering the gut microbiota composition and increasing the levels of gut microbiota-derived SCFAs.
Subject(s)
Fatty Acids, Volatile , Gastrointestinal Microbiome , Lung , Orthomyxoviridae Infections , Pediococcus pentosaceus , Probiotics , Animals , Gastrointestinal Microbiome/drug effects , Fatty Acids, Volatile/metabolism , Mice , Probiotics/pharmacology , Lung/microbiology , Lung/metabolism , Lung/drug effects , Disease Models, Animal , Cytokines/metabolism , MaleABSTRACT
Hyperuricemia (HUA) is a widespread metabolic disorder. Probiotics have drawn increasing attention as an adjunctive treatment with fewer side effects. However, thus far the effective strains are limited and the mechanisms for their serum uric acid (SUA)-lowering effect are not well understood. Along this line, we conducted the current study using a hyperuricemia mouse model induced by potassium oxonate and adenine. A novel strain of Lactococcus cremoris named D2022 was identified to have significant SUA-lowering capability. Lactococcus cremoris D2022 significantly reduced SUA levels by inhibiting uric acid synthesis and regulating uric acid transportation. It was also found that Lactococcus cremoris D2022 alleviated HUA-induced renal inflammatory injury involving multiple signaling pathways. By focusing on the expression of NLRP3-related inflammatory genes, we found correlations between the expression levels of these genes and free fatty acid receptors (FFARs). In addition, oral administration of Lactococcus cremoris D2022 increased short-chain fatty acids (SCFAs) in cecal samples, which may be one of the mechanisms by which oral probiotics alleviate renal inflammation. Serum untargeted metabolomics showed changes in a variety of serum metabolites associated with purine metabolism and inflammation after oral administration of Lactococcus cremoris D2022, further confirming its systemic bioactivity. Finally, it was proved that Lactococcus cremoris D2022 improved intestinal barrier function. In conclusion, Lactococcus cremoris D2022 can alleviate HUA and HUA-induced nephropathy by increasing the production of SCFAs in the gut and systemic metabolism.
Subject(s)
Hyperuricemia , Kidney , Lactococcus , Probiotics , Uric Acid , Animals , Hyperuricemia/drug therapy , Mice , Probiotics/pharmacology , Probiotics/administration & dosage , Male , Uric Acid/blood , Kidney/metabolism , Gastrointestinal Microbiome/drug effects , Inflammation , Disease Models, Animal , Mice, Inbred C57BLABSTRACT
Developing high-performance organic-inorganic ultraviolet (UV) photodetectors (PDs) has attracted considerable attention. However, this development has been hindered due to poor directional charge-transfer ratios in transport layers, excessive costs, and an ambiguous underlying mechanism. To tackle these challenges, we constructed a heterojunction of economic Mg-doped ZnO (MgZnO) nanorods and poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) [PEDOT:PSS (P:P)] that utilizes dipole field-driven spontaneous polarization to enhance photogenerated charge kinetics. As a result, the proposed heterojunction has an improved noise equivalent power of 3.16 × 10-11 W Hz-1/2), a normalized detection rate (D*) of 8.96 × 109 jones, and external quantum efficiency comparable to other ZnO-based devices. Notably, the prepared PDs showed a photocurrent of 4.8 × 10-3 µA under a faint UV light having an intensity of 1 × 10-5 W cm-2, exceeding the performance of the most state-of-the-art ZnO-based UV sensors. The introduction of Mg into ZnO is responsible for the high performance, as it causes a lattice mismatch and distortion of the Mg-doped ZnO unit cell. It results in improved dipole movement and the creation of a dipole field, accelerating the directional electron-transfer process. Using a dipole field to manipulate the migration and transport of photogenerated carriers represents a promising approach for achieving outstanding performance in UV PDs.
ABSTRACT
The excessive enrichment of nitrate in the environment can be converted into ammonia (NH3) through electrochemical processes, offering significant implications for modern agriculture and the potential to reduce the burden of the Haber-Bosch (HB) process while achieving environmentally friendly NH3 production. Emerging research on electrocatalytic nitrate reduction (eNitRR) to NH3 has gained considerable momentum in recent years for efficient NH3 synthesis. However, existing reviews on nitrate reduction have primarily focused on limited aspects, often lacking a comprehensive summary of catalysts, reaction systems, reaction mechanisms, and detection methods employed in nitrate reduction. This review aims to provide a timely and comprehensive analysis of the eNitRR field by integrating existing research progress and identifying current challenges. This review offers a comprehensive overview of the research progress achieved using various materials in electrochemical nitrate reduction, elucidates the underlying theoretical mechanism behind eNitRR, and discusses effective strategies based on numerous case studies to enhance the electrochemical reduction from NO3 - to NH3. Finally, this review discusses challenges and development prospects in the eNitRR field with an aim to guide design and development of large-scale sustainable nitrate reduction electrocatalysts.
ABSTRACT
Increasing evidence shows that some probiotics can improve vaccine responses as adjuvants. This study aimed to evaluate the effect of Pediococcus pentosaceus MIANGUAN (PPM) on SARS-CoV-2 vaccine-elicited immune response in mice. Six-week-old female ICR mice were primed and boosted with SARS-CoV-2 vaccine intramuscularly at weeks 0 and 4, respectively. Mice were gavaged with PPM (5 × 109 CFU/mouse) or PBS (control) for 3 days immediately after boosting vaccination. Compared to the control, oral PPM administration resulted in significantly higher levels of RBD-specific IgG binding antibodies (> 2.3-fold) and RBD-specific IgG1 binding antibodies (> 4-fold) in the serum. Additionally, PPM-treated mice had higher titers of RBD-specific IgG binding antibodies (> 2.29-fold) and neutralization antibodies (> 1.6-fold) in the lung compared to the control mice. The transcriptional analyses showed that the B cell receptor (BCR) signaling pathway was upregulated in both splenocytes and BAL cells in the PPM group vs. the control group. In addition, the number of IFN-γ-producing splenocytes (mainly in CD4 + T cells as determined by flow cytometry) in response to restimulation of RBD peptides was significantly increased in the PPM group. RNA sequencing showed that the genes associated with T cell activation and maturation and MHC class II pathway (CD4, H2-DMa, H2-DMb1, H2-Oa, Ctss) were upregulated, suggesting that oral administration of PPM may enhance CD4 + T cell responses through MHC class II pathway. Furthermore, PPM administration could downregulate the expression level of proinflammatory genes. To conclude, oral administration of PPM could boost SARS-CoV-2 vaccine efficacy through enhancing the specific humoral and cellular immunity response and decrease the expression of inflammation pathways.
Subject(s)
Antibodies, Viral , Mice, Inbred ICR , Pediococcus pentosaceus , Probiotics , Animals , Female , Mice , Probiotics/administration & dosage , Pediococcus pentosaceus/immunology , Antibodies, Viral/blood , COVID-19 Vaccines/immunology , SARS-CoV-2/immunology , Vaccination , COVID-19/prevention & control , COVID-19/immunology , Immunoglobulin G/blood , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/pharmacologyABSTRACT
Two Gram-stain-negative, non-spore-forming, rod-shaped, and obligately aerobic bacteria, designated strains CX-624T and cx-311, were isolated from soil samples in Qinghai Province, China. The two strains grew best at 28 °C on the plate with Tryptone soya agar (TSA). Cells formed circular, convex, translucent, smooth, and orange colonies with approximately 1.0 mm diameter after 2 days of incubation on TSA at 28 °C. The strains were oxidase-negative and catalase-positive. The predominant cellular fatty acids were iso-C15â:â0 and anteiso-C15â:â0, and major polar lipids included phosphatidylethanolamine, an unidentified aminophospholipid, four unidentified lipids and an aminolipid. MK-6 was the sole menaquinone in strain CX-624T. Comparative analysis of the nearly full-length 16S rRNA gene sequences showed strains CX-624T and cx-311 were member of the family Weeksellaceae, with the highest similarity to Kaistella haifensis H38T (96.66â%), Epilithonimonas pallida DSM 18015T (96.59â%), and Chryseobacterium gambrini DSM 18014T (96.53â%). Both phylogenetic analysis of the 16S rRNA gene and 177 core genes revealed that strains CX-624T and cx-311 formed an independent clade. Average nucleotide identity values (< 72.64â%), average amino-acid identity values (<72.61â%) and digital DNA-DNA hybridization (< 21.10â%) indicated that the strains CX-624T and cx-311 should constitute a novel genus. The DNA G+C contents of strains CX-624T and cx-311 were 43.0 mol% and 42.7 mol%. According to the data obtained in this study, strain CX-624T represents a novel species belonging to a novel genus of the Weeksellaceae, for which the name Marnyiella aurantia gen. nov., sp. nov. is proposed. The type strain is CX-624T (=GDMCC 1.1714T = JCM 33925T).
Subject(s)
Fatty Acids , Flavobacteriaceae , Fatty Acids/chemistry , Phylogeny , RNA, Ribosomal, 16S/genetics , DNA, Bacterial/genetics , Base Composition , Bacterial Typing Techniques , Sequence Analysis, DNA , Vitamin K 2ABSTRACT
Photocatalytic oxidation is an efficient and promising technology for reducing indoor pollution levels of formaldehyde (HCHO). However, developing efficient and low-cost photocatalysts for the removal of HCHO remains challenging due to the time-consuming and expensive nature of traditional "trial and error" and "directed research" approaches. To achieve this goal, first-principles density functional theory (DFT) calculations were conducted to high-throughput screen candidate TM-C3N6 photocatalysts for high-performance degradation of HCHO. The results revealed that Zr-C3N6 and Hf-C3N6 in functionalizing C3N6 with 28 transition metals showed excellent adsorption energy of HCHO, boosting the highly effective capture of HCHO. Meanwhile, an excellent adsorption performance mechanism was further elicited by the electric structure-property relationship. In addition, reaction mechanisms for HCHO degradation and three potential reaction pathways for HCHO degradation were systematically evaluated. Our findings indicated that hydroxyl-assisted dehydrogenation and oxygen-assisted dehydrogenation are the most favorable pathways, with rate-limiting steps involving the formation of ËOH and ËO radicals. Overall, this study may provide new insights into a high-throughput screening of novel photocatalysts that are both high-performing and low-cost for the removal of formaldehyde. This, in turn, can accelerate the experimental development process and reduce the associated costs and time consumption.
ABSTRACT
Simultaneously achieving high activity for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is the key to constructing rechargeable Zn-air batteries (ZABs). Here the complexation of 1,10-phenanthroline and the spatial confinement effect of closo-[B12 H12 ]2- are used to solidify metal-boron-cluster-organic-polymers on the surface of SiO2 microspheres to construct a bifunctional oxygen electrocatalyst (FeBCN/NHCS). Driven by FeBCN/NHCS, the half-wave-potential of ORR surpasses that of the Pt/C catalyst, reaching 0.893 V versus RHE, and the overpotential (η10 ) of OER is as low as 361 mV. The ZABs of FeBCN/NHCS as an air cathode not only have high power density and specific capacity, but also have charge-discharge durability. The FeBCN/NHCS is not only related to the high specific surface area, but also the high exposure rate of single-atom Fe and the doping of heteroatom B. This study provides an efficient oxygen electrocatalyst and also contributes wisdom to the acquisition of highly active oxygen electrocatalyst.
ABSTRACT
Harnessing abundant renewable resources and pollutants on a large scale to address environmental challenges, while providing sustainable freshwater, is a significant endeavour. This study presents the design of fully functional solar vaporization devices (SVD) based on organic-inorganic hybrid nanocomposites (CCMs-x). These devices exhibit efficient photothermal properties that facilitate multitargeted interfacial reactions, enabling simultaneous catalysis of sewage and desalination. The localized interfacial heating generated by the photothermal effect of CCMs-x triggers surface-dominated catalysis and steam generation. The CCMs-x SVD achieves a solar water-vapor generation rate of 1.41 kg m-2 h-1 (90.8%), and it achieves over 95% removal of pollutants within 60 min under one-sun for practical application. The exceptional photothermal conversion rate of wastewater for environmental remediation and water capture is attributed to customized microenvironments within the system. The integrated parallel reaction system in SVD ensures it is a real-life application in multiple scenarios such as municipal/medical wastewater and brine containing high concentrations. Additionally, the SVD exhibits long-term durability, antifouling functionality toward complex ionic contaminants. This study not only demonstrates a one-stone-two-birds strategy for large-scale direct production of potable water from polluted seawater, but also opens up exciting possibilities for parallel production of energy and water resources.
ABSTRACT
Convincing evidence has suggested the health potentials of oolong tea (OT) on gut microbiota homeostasis; however, limited population-based studies exist regarding the effect of OT consumption on human gut microbial and metabolic profile. This pilot study explored gut microbial and metabolic changes in healthy adults with a 3-week oolong tea intake. Our findings showed that OT treatment significantly altered gut microbial diversity (Shannon index, 5.4±0.1 vs. 5.7±0.1 pre- and post-OT treatment), reorganized gut microbiota composition, enriched Bacteroides and Prevotella, decreased Megamonas, and improved gastrointestinal function. Also, gut microbes from overweight subjects with BMI >23.9 exhibited greater responses to OT treatment compared with normal-weight counterparts. Metabolomic analysis identified OT intake-induced 23 differential metabolites and 10 enriched metabolic pathways. This study may provide new insights into the association among OT intervention, host gut microbiome and metabolic profile, and improve the knowledge of clinical strategies and personalized nutrition.
Subject(s)
Gastrointestinal Microbiome , Adult , Humans , Pilot Projects , Polyphenols , Multiomics , Tea , MetabolomeABSTRACT
Piezoelectric mesocrystals as defective materials have been demonstrated to possess adsorptive and catalytic properties in redox reactions. However, there is still a lack of research on the quantitative relationship between the defect concentration and the piezocatalytic performance in piezoelectric mesocrystals. Herein, twin-hierarchical structure ZnO piezoelectric mesocrystals are taken with different oxygen-vacancies (OVs) concentrations to quantitatively investigate the effect of defect content on the peroxymonosulfate (PMS) piezo-activation in water purification. The ZnO piezoelectric mesocrystal with moderate OVs concentration exhibits a rapid antibiotic ornidazole (ORZ) pollutants degradation rate (0.034 min-1 ) and achieves a high PMS utilization efficiency (0.162) that exceeds the most state-of-the-art catalytic processes, while excessive OVs suppressed the piezocatalytic performance. Through calculations of electron property and reactants affinity, a quantitative relationship between OVs concentration and piezocatalytic properties is established. The ZnO mesocrystal with moderate OVs concentration realized increased electron delocalization, reduced charge transfer barrier, and enhanced reactants affinity, thus accelerating the kinetics of PMS activation. This work provides theoretical guidance for the application of defect engineering in mesocrystal to realize enhanced piezocatalytic performance.
ABSTRACT
Cold-brewed jasmine tea (CB-JT) is regarded to possess characteristic flavors and health benefits as a novel resource of functional tea beverages. To investigate the molecular mechanisms underlying CB-JT-mediated protective effects on obesity, we evaluated the serum biochemistry, histological condition, glucose tolerance, gene expression profile and intestinal microbial diversity in high-fat diet (HFD)-fed mice. Our results demonstrate that cold-brewed jasmine tea can significantly attenuate HFD-induced body weight gain, abnormal serum lipid levels, fat deposition, hepatic injury, inflammatory processes as well as metabolic endotoxemia. CB-JT also modified the microbial community composition in HFD-fed mice and altered the balance to one closely resembled that of the control group. The differential abundance of core microbes in obese mice was reversed by CB-JT treatment, including an increment in the abundance of Blautia, Mucispirillum, and Bilophila as well as a decrease in the abundance of Alloprevotella. CB-JT was proved to regulate the mRNA expression levels of lipid metabolism-related genes such as Leptin, Pgc1a Il6, and Il1b in the adipose tissue coupled with Cyp7a1, Lxra, Srebp1c, and Atgl in the liver. These findings indicate that cold-brewed jasmine tea might be served as a potential functional tea beverage to prevent obesity and gut microbiota dysbiosis.
Subject(s)
Gastrointestinal Microbiome , Jasminum , Animals , Mice , Diet, High-Fat/adverse effects , Tea/chemistry , Dysbiosis/metabolism , Obesity/etiology , Obesity/prevention & control , Obesity/metabolism , Mice, Inbred C57BLABSTRACT
To rapidly design nitrogen reduction reaction (NRR) electrocatalysts with superior activity and selectivity is a great challenge. Herein, we propose a simple mixture strategy including three screening steps and a descriptor to predict NRR electrocatalysts with outstanding activity and selectivity based on density functional theory (DFT). Twenty-eight candidate transition-metal dimers anchored on nitrogen-doped graphene were systematically investigated through our mixture strategy. The results show that VRu-NC exhibits a high NRR activity and suppression of the competitive hydrogen evolution reaction (HER) following the mixed mechanism with a favorable limiting potential (UL) of -0.21 V. Finally, the mechanism of the catalytic reaction pathway was investigated according to the profile of atomic orbitals and electronic properties. This work proposes a feasible strategy for rapid screening of the high-performance of double atomic electrocatalysts with excellent activity and selectivity for the NRR.
ABSTRACT
Obesity is a major public health issue worldwide. Oolong tea (OT), which is partially fermented from Camellia sinensis leaves, has proven health benefits and potential preventive applications in multiple studies. However, research on the role of OT in obesity prevention and potential mechanisms is still limited. The purpose of this study was to investigate the modulatory effects of OT intervention on high-fat diet (HFD)-induced obesity and gut microbiota dysbiosis using an obese mouse model. Our results showed that 8-week OT supplementation with 93.94% polyphenols significantly decreased body weight gain, adipose tissue mass, and serum levels of triglyceride (2.60 mmol/L), cholesterol (5.49 mmol/L), and low-density lipoprotein cholesterol (0.61 mmol/L) in HFD-fed mice. Meanwhile, OT intervention was observed to improve fat accumulation, hepatic damage, glucose intolerance, and endotoxemia and alleviate inflammation by decreasing the levels of pro-inflammatory factors. OT also upregulated the expression of genes including Srebf1, Ppara, Lxra, Pgc1a, and Hsl and downregulated the expression of genes including Leptin, Il-6, and Il-1b. In addition, the gut dysbiosis characterized by decreased flora diversity and increased Firmicutes/Bacteroidetes ratio in obese mice was recovered by OT intervention. Certain differentially abundant microbes caused by HFD feeding, including Enterococcus, Intestinimonas, Blautia, and Bilophila, were also improved by OT treatment. This study demonstrated that OT, as a novel resource of dietary polyphenols, exhibited a protective effect on HFD-induced obesity and gut microbiota disorder.
ABSTRACT
Photocatalytic water splitting is one of the promising approaches to solving environmental problems and energy crises. However, the sluggish 4e- transfer kinetics in water oxidation half-reaction restricts the 2e- reduction efficiency in photocatalytic water splitting. Herein, cobalt vanadate-decorated polymeric carbon nitride (named CoVO/PCN) was constructed to mediate the carrier kinetic process in a photocatalytic water oxidation reaction (WOR). The photocatalysts were well-characterized by various physicochemical techniques such as XRD, FT-IR, TEM, and XPS. Under UV and visible light irradiation, the O2 evolution rate of optimized 3 wt% CoVO/PCN reached 467 and 200 µmol h-1 g-1, which were about 6.5 and 5.9 times higher than that of PCN, respectively. Electrochemical tests and PL results reveal that the recombination of photogenerated carriers on PCN is effectively suppressed and the kinetics of WOR is significantly enhanced after CoVO introduction. This work highlights key features of the tuning carrier kinetics of PCN using charge-conducting materials, which should be the basis for the further development of photocatalytic O2 reactions.
ABSTRACT
HMOs (human milk oligosaccharides) are the third most important nutrient in breast milk. As complex glycans, HMOs play an important role in regulating neonatal intestinal immunity, resisting viral and bacterial infections, displaying anti-inflammatory characteristics, and promoting brain development. Although there have been some previous reports of HMOs, a detailed literature review summarizing the structure-activity relationships and dose-dependent effects of HMOs is lacking. Hence, after introducing the structures and synthetic pathways of HMOs, this review summarizes and categorizes identified structure-function relationships of HMOs. Differential mechanisms of different structural HMOs utilization by microorganisms are summarized. This review also emphasizes the recent advances in the interactions between different health benefits and the variance of dosage effect based on in vitro cell tests, animal experiments, and human intervention studies. The potential relationships between the chemical structure, the dosage selection, and the physiological properties of HMOs as functional foods are vital for further understanding of HMOs and their future applications.
Subject(s)
Milk, Human , Oligosaccharides , Animals , Humans , Intestines/microbiology , Milk, Human/chemistry , Oligosaccharides/chemistry , Structure-Activity RelationshipABSTRACT
BACKGROUND: The aim of this study was to investigate the roles of keratin 4 (KRT4) gene in the development of human white sponge nevus (WSN). METHODS: Transgenic mice were created using the microinjection method with pcDNA3.1 vectors expressing KRT4 wild-type (WT) gene and E520K mutation. Polymerase chain reaction (PCR) and Western blotting were used to identify the genotype of transgenic founders and their filial generations. Expression of KRT4 in mouse oral mucosa was characterized by immunohistochemistry (IHC), and the whole epithelium layer of transgenic mice was observed using transmission electron microscope (TEM). RESULTS: The positive rate of KRT4 transgenic mice in F1 generation was 45.5%. Expression level of KRT4 protein was significantly higher in 2-month-old transgenic mice than WT mice. Furthermore, all the epithelial lamina of 3-month-old transgenic mice showed reduced staining of KRT4. The surface and spinous layers were full of hyalocytes and bubble cells, which are similar to the clinical symptoms of WSN. For the ultrastructure, both tonofilaments and Odland bodies increased. CONCLUSIONS: Our study indicated the mutated KRT4 gene may play important roles in the pathogenesis of WSN.
Subject(s)
Keratin-4/metabolism , Leukokeratosis, Hereditary Mucosal/metabolism , Mouth Diseases/metabolism , Animals , Epithelium/pathology , Female , Humans , Immunohistochemistry , Keratin-4/genetics , Leukokeratosis, Hereditary Mucosal/genetics , Leukokeratosis, Hereditary Mucosal/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Mouth Diseases/genetics , Mouth Diseases/pathology , Mouth Mucosa/metabolism , Mouth Mucosa/pathology , MutationABSTRACT
The seven-amino acid truncated (7ND) protein is an N-terminal deletion mutant of monocyte chemoattractant protein-1 (MCP-1) and it functions as a dominant-negative inhibitor. 7ND and wild-type MCP-1 form a heterodimer, which binds to MCP-1 receptors and inhibits monocyte chemotaxis. In the present study, the 7ND protein was cloned, expressed and purified. An MTT assay revealed that the proliferation of oral squamous cell carcinoma (OSCC) SCC25 cells was not affected following 3 days of treatment with synthetic 7ND protein. Serial dilutions of the 7ND protein were tested for monocyte migration and osteoclast differentiation, and tartrate-resistant acid phosphatase staining demonstrated that significantly fewer osteoclasts were differentiated from cluster of differentiation 14+ (CD14+) monocytes using magnetic activated cell sorting. Immunofluorescence confirmed these results and significantly less F-actin staining was observed in 7ND-treated osteoclasts. Furthermore, bone invasion was examined by subcutaneously injecting SCC25 cells into the area overlaying the calvariae of nude mice. The results demonstrated that the average tumor volume of SCC25 cells with 7ND protein was similar to the average volume of tumors formed by untreated SCC25 cells. Flow cytometric analysis suggested that the CD14+ subpopulation in the bone marrow of 7ND-treated mice was reduced compared with that of untreated mice. Micro-computed tomography imaging revealed significantly less bone resorption in the calvariae injected with SCC25 cells plus the 7ND protein. Taken together, the results of the present study demonstrated the potential therapeutic value of the 7ND protein. The 7ND MCP-1 variant not only functions in vitro to inhibit osteoclast differentiation, but also reduces the progression of bone invasion by OSCC cells in vivo.