ABSTRACT
Klebsiella pneumoniae is a primary cause of clinical mastitis in dairy cows, with prevention being crucial, as treatments often fail due to antimicrobial resistance. Recent studies identified type I fimbrial antigens of K. pneumoniae as promising vaccine candidates, but there are limited research data. In this study, 3 fimbriae genes (fimA, fimC and fimG) were cloned and recombinantly expressed in Escherichia coli and their protective efficacy against K. pneumoniae evaluated in a mouse model. All 3 recombinant fimbriae proteins elicited strong humoral immune responses in mice, significantly increasing IgG, IgG1 and IgG2a. Notably, using a model of mice challenged with an intraperitoneal injection of bacteria, FimG significantly reduced bacterial loads in the spleen and lung, whereas FimA and FimC had limited protection for these organs. Either active or passive immunization with FimG produced substantial protective effects in mice challenged with K. pneumoniae LD100; in contrast, the mortality rate in the FimA-immunized group was similar to that of the control group, whereas FimC had weak protection. We concluded that the FimG recombinant protein vaccine had a favorable protective effect, with potential for immunization against K. pneumoniae mastitis.
Subject(s)
Antibodies, Bacterial , Bacterial Vaccines , Disease Models, Animal , Fimbriae Proteins , Klebsiella Infections , Klebsiella pneumoniae , Mice, Inbred BALB C , Animals , Klebsiella pneumoniae/immunology , Mice , Klebsiella Infections/prevention & control , Klebsiella Infections/immunology , Klebsiella Infections/microbiology , Fimbriae Proteins/immunology , Fimbriae Proteins/genetics , Female , Bacterial Vaccines/immunology , Bacterial Vaccines/administration & dosage , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology , Recombinant Proteins/immunology , Fimbriae, Bacterial/immunology , Immunoglobulin G/blood , Immunity, HumoralABSTRACT
Obesity is becoming a worldwide pandemic. Interfacial engineering of food lipid is expected to inhibit diet-induced obesity without damage to the eating enjoyment brought by high-fat diets. Unfortunately, this strategy has not been achieved yet. After screening different plant proteins, bromelain and papain were found to form wormlike and long-straight protein fibrils, respectively. The conversion of long-straight amyloid-like fibrils to wormlike fibrils was demonstrated in the fibrillation of bromelain. Using oil-in-water high internal phase emulsions (HIPEs) as a proof of concept, bromelain fibrils showed dramatically stronger interfacial stabilization capabilities than papain fibrils with high application potentials in the real-world formulation of high-fat food products such as mayonnaise. Compared with papain fibrils, oral administration of HIPEs stabilized by bromelain fibrils resulted in substantially higher fecal lipid contents and significantly decreased expression levels of the genes related to lipid absorption and transport in the intestine, including CD36, FATP-2, FATP-4, and APOA-4, without a difference in intervening gut microbiota. Consequently, dramatically less lipid absorption in the small intestine, markedly smaller chylomicron particles in the plasma, lower serum triglycerides, and controlled energy and lipid metabolism, as well as the inhibition of adipose expansion and overweight, were observed in the group with gavage of HIPEs stabilized by the bromelain fibrils rather than the papain fibrils. Furthermore, with the same calorie, substitution of all the fat in the standard high-fat feed of mice with the HIPEs emulsified by the bromelain fibrils showed a significantly stronger effect than the ones prepared by the papain fibrils on preventing high-fat-diet (HFD)-induced obesity including alleviation of adipose expansion and inflammation as well as fatty liver, also via inhibiting the absorption and transport of lipid in the intestine. The effect is ascribed to the suppressed lipolysis caused by a more compact and elastic interfacial layer formed by the wormlike fibrils than that of the long-straight fibrils, which are resistant to gastric environments and replacement by bile acids in digestion. Therefore, we provide an appealing and general strategy for controlling obesity by reducing the supply of free fatty acids (FAs) for absorption in the enteric lumen through protein fibril polymorphisms at the interface.
Subject(s)
Obesity , Papain , Animals , Obesity/metabolism , Mice , Papain/metabolism , Papain/chemistry , Bromelains/pharmacology , Bromelains/chemistry , Bromelains/metabolism , Mice, Inbred C57BL , Male , Diet, High-Fat , Emulsions/chemistry , Adipose Tissue/metabolism , Adipose Tissue/drug effects , Lipid Metabolism/drug effectsABSTRACT
Dextromethorphan (DXM) is a widely utilized central antitussive agent, which is frequently abused by individuals seeking its recreational effect. But DXM overdose can cause some adverse effects, including brain damage, loss of consciousness, and cardiac arrhythmias, and hence its detection is significant. Herein, an electrochemical sensor based on a Cu-coordinated molecularly imprinted polymer (Cu-MIP) was fabricated for its detection. For constructing the sensor, nitrogen-doped carbon nanosheets (CCNs) were prepared through calcining chitin under an argon atmosphere, and molybdenum disulfide (MoS2) was allowed to grow on their surface. Subsequently, the obtained MoS2/CCNs composite was employed to modify a glassy carbon electrode (GCE), and the Cu-MIP was electrodeposited on the electrode in a Cu-1,10-phenanthroline (Cu-Phen) solution containing DXM, where Cu2+ played a role in facilitating electron transfer and binding DXM. Due to the large specific surface area, good electrocatalytic properties and recognition of the resulting composite, the resulting Cu-MIP/MoS2/CCNs/GCE showed high selectivity and sensitivity. Under optimized experimental conditions, the peak current of DXM and its concentration exhibited a good linear relationship over the concentration range of 0.1-100 µM, and the limit of detection (S/N = 3) was 0.02 µM. Furthermore, the electrochemical sensor presented good stability, and it was successfully used for the determination of DXM in pharmaceutical, human serum and urine samples.
Subject(s)
Carbon , Copper , Dextromethorphan , Disulfides , Electrochemical Techniques , Molecularly Imprinted Polymers , Molybdenum , Molybdenum/chemistry , Disulfides/chemistry , Dextromethorphan/analysis , Dextromethorphan/chemistry , Dextromethorphan/urine , Copper/chemistry , Electrochemical Techniques/methods , Carbon/chemistry , Molecularly Imprinted Polymers/chemistry , Chitin/chemistry , Humans , Limit of Detection , Electrodes , Antitussive Agents/chemistry , Antitussive Agents/analysis , Antitussive Agents/urineABSTRACT
With the rapid science and technology advancement, the oil-water separation in oily wastewater has become an urgent problem, especially the emulsified oil-water mixtures. Hollow carbon spheres (HCSs) have tremendous potential in separating oil-water emulsions due to their rich porous channels and high surface-to-volume ratio. In this work, as-prepared chitosan/poly(γ-glutamic acid) nanoparticles crosslinked by Ni2+ (Ni2+/CS/γ-PGA NPs) were used as carbon precursor to fabricate HCSs. This strategy separated the formation process of the biomolecular microspheres and the carbonization process. Especially, the Ni2+/CS/γ-PGA NPs were fabricated from the self-assembly of chitosan and γ-PGA in aqueous solution and the crosslinking of Ni2+ via the electrostatic interactions, facilitating the formation of biomolecular microspheres and making the usable of biomolecule-based carbon precursors diversity. After lyophilization, Ni2+/CS/γ-PGA NPs powder was obtained, which was then carbonized in a tube furnace under N2 atmosphere. During the carbonization process, the nickel species aggregated together to form the core of nickel@carbon nanoparticles, and carbon formed the shell. At last, nickel nanoparticles were removed from the carbon framework by hydrochloric acid, obtaining HCSs with super-hydrophobicity and lipophilicity. The as-prepared HCSs exhibited excellent separation performance in oil-in-water emulsions.
Subject(s)
Chitosan , Nanoparticles , Emulsions , Carbon , Nickel , WaterABSTRACT
Lonicera japonica polysaccharides (LJPs) exhibit anti-aging effect in nematodes. Here, we further studied the function of LJPs on aging-related disorders in D-galactose (D-gal)-induced ICR mice. Four groups of mice including the control group, the D-gal-treated group, the intervening groups with low and high dose of LJPs (50 and 100 mg/kg/day) were raised for 8 weeks. The results showed that intragastric administration with LJPs improved the organ indexes of D-gal-treated mice. Moreover, LJPs improved the activity of superoxide dismutase (SOD), catalase (CAT) as well as glutathione peroxidase (GSH-Px) and decreased the malondialdehyde (MDA) level in serum, liver and brain. Meanwhile, LJPs restored the content of acetylcholinesterase (AChE) in the brain. Further, LJPs reversed the liver tissue damages in aging mice. Mechanistically, LJPs alleviate oxidative stress at least partially through regulating Nrf2 signaling. Additionally, LJPs restored the gut microbiota composition of D-gal-treated mice by adjusting the Firmicutes/Bacteroidetes ratio at the phylum level and upregulating the relative abundances of Lactobacillaceae and Bifidobacteriacesa. Notably, the KEGG pathways involved in hazardous substances degradation and flavone and flavonol biosynthesis were significantly enhanced by LJPs treatment. Overall, our study uncovers the role of LJPs in modulating oxidative stress and gut microbiota in the D-gal-induced aging mice.
Subject(s)
Gastrointestinal Microbiome , Lonicera , Mice , Animals , Antioxidants/pharmacology , Galactose/pharmacology , Mice, Inbred ICR , Acetylcholinesterase/metabolism , Oxidative Stress , Polysaccharides/pharmacology , Superoxide Dismutase/metabolism , Malondialdehyde/metabolismABSTRACT
OBJECTIVE: This study aimed to investigate the composite effects of different kinds of phthalates on depression risk in the U.S population. METHODS: 11731 participants were included from the National Health and Nutrition Examination Survey (NHANES), a national cross-sectional survey. Twelve urinary phthalate metabolites were used to evaluate the level of phthalates exposure. Phthalates levels were devided into four quartiles. High phthalate was defined as having values in the highest quartile. RESULTS: Urinary mono-isobutyl phthalate (MiBP) and mono-benzyl phthalate (MBzP) were estimated as the independent risk factors for depression by mutivariate logistic regression analyses. Compared with the lowest quartile group of MiBP or MBzP, an incrementally higher risk of depression and moderate/severe depression was observed in the highest quartile (all Ptrend <0.05). It was observed that incrementally higher risk of depression and moderate/severe depression were associated with more numbers of high phthalates parameter (Ptrend <0.001 and Ptrend = 0.003, respectively). A significant interaction between race (Non-Hispanic Black vs. Mexican American) and 2 parameters (having value in the highest quartile of both MiBP and MBzP) was detected for depression (Pinteraction = 0.023) and moderate/severe depression (Pinteraction = 0.029). CONCLUSION: Individuals with more numbers of high phthalates parameter were at higher risk of depression and moderate/severe depression. Non-Hispanic Black participants were more likely to be affected by high levels of MiBP and MBzP exposure than Mexican American participants.
Subject(s)
Environmental Pollutants , Phthalic Acids , Humans , Nutrition Surveys , Cross-Sectional Studies , Depression/chemically induced , Depression/epidemiology , Race Factors , Phthalic Acids/urine , Environmental Pollutants/toxicity , Environmental Pollutants/urine , Environmental Exposure/adverse effectsABSTRACT
BACKGROUND: Colorectal cancer (CRC) is a prevalent malignancy of the gastrointestinal. Circular RNAs (circRNAs) act as important roles in CRC malignant progression. However, the role of circ_0039857 in CRC is still unclear. Therefore, this study aimed to explore the function and mechanism of hsa_circ_0039857 in the CRC. METHODS: The mRNA and protein expression were measured via RT-qPCR. RNase R assay and Actinomycin D were employed to evaluate the stability of circ_0039857. Functional experiments, such as proliferation and apoptosis, were applied to study the function of circ_0039857 in CRC cells. The underlying mechanisms of circ_0039857 were then analyzed by bioinformatics, dual-luciferase reporter gene assay, RNA pull-down and rescue experiments. RESULTS: We revealed that circ_0039857 was significantly enhanced in CRC. Circ_0039857 was stabler than linear RNA in cells and valuable for the disease diagnosis. In addition, circ_0039857 knockdown inhibited proliferation and promoted apoptosis. Mechanistically, circ_0039857 positively regulated the expression of RAB32 via sponging miR-338-3p. CONCLUSION: This study demonstrated that circ_0039857 knockdown suppressed CRC malignant progression through miR-338-3p/RAB32 axis. Most importantly, this will help us to better understand the circRNA network in CRC, and may find potential biomarkers and targets for CRC clinical treatment.
Subject(s)
Colorectal Neoplasms , MicroRNAs , Humans , Colorectal Neoplasms/pathology , Cell Proliferation/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Circular/genetics , Biomarkers , rab GTP-Binding Proteins/genetics , rab GTP-Binding Proteins/metabolismABSTRACT
Photonic switches have attractive application prospects in optical communication data networks that require dynamic reconfiguration. Integrating optical switching devices with optical fiber, the most widely deployed photonic technology platform, can realize signal transmission and processing in practical applications. Here, we demonstrate the multilevel optical switching using the phase-change material Ge2Sb2Te5 (GST) integrated on a graded-index multimode fiber. This switching process works by exploiting the significant difference in extinction coefficient between the crystalline state and the amorphous state of the GST. Using GST to achieve the switch function, no external energy source is needed to maintain the existing state of the switch, and the device is nonvolatile. This multi-level optical switch is an all-fiber integrated device. We apply GST to the end facets of the graded-index multimode fiber by magnetron sputtering, which is a reflective structure. A pulsing scheme is used to control the optical propagation state of the optical modulation signal to realize the switching function. It can store up to 11 non-volatile reliable and repeatable levels encoded by the pump source laser with a wavelength of 1550 nm. At the same time, the switching process between states is on the order of hundreds of nanoseconds. The present experimental results demonstrate the feasibility of 11 multilevel states in the field of optical fibers commonly used in communications. It can be well coupled with the all-fiber terminal device. It also shows that the device is still applicable in the 1525 nmâ¼1610 nm broadband range, promising for designing future multilevel photonic switches and memory devices.
ABSTRACT
Objective: This study aimed to evaluate the relationship between daily dietary intake of fiber (DDIF) and short sleep duration (SSD) in the presence of di(2-ethylhexyl) phthalate. Methods: Data of 13,634 participants in this study were collected from the National Health and Nutrition Examination Survey (NHANES). The sum of urinary mono-2-ethyl-5-carboxypentyl phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl)-hexyl phthalate, and mono-(2-ethyl-5-oxohexyl) phthalate was used to evaluate the level of di(2-ethylhexyl) phthalate (DEHP) exposure. The ln-transformed urinary creatinine-corrected DEHP [ln(DEHP/UCr)] level was used in the statistical models. DDIF was divided into tertiles (<5.77 g/1,000 kcal, 5.77-9.04 g/1,000 kcal, and ≥9.04 g/1,000 kcal). Results: The 13,634 participants included in this study were classified into two groups according to sleep duration. The dose response analysis showed that higher ln(DEHP/UCr) was related to a higher risk of SSD (<7 h and <6 h). Participants in the highest vs. the lowest quartile of DEHP were found to be at increased risk of SSD (<7 h, <6 h, and <5 h). The result of risk of SSD <7 h was OR 1.57, 95% CI, 1.40-1.76; Ptrend <0.001, of SSD <6 h was OR 1.38, 95% CI, 1.18-1.61; Ptrend <0.001, and of SSD <5 h was OR 1.45, 95% CI, 1.13-1.86; Ptrend <0.001. DEHP exposure was found to be associated with SSD <7 h in a sex-specific manner (Pinteraction = 0.033). A significant interaction between ln(DEHP/UCr) and DDIF(tertiles1 vs. tertiles2) (Pinteraction = 0.02) was detected for SSD <7 h. Conclusion: Our results showed that there was a harmful association between DEHP exposure and SSD (<7 h, <6 h, and <5 h). The ameliorative effects of median level of DDIF on SSD <7 h in the presence of DEHP exposure were observed in this study.
ABSTRACT
Optical switches based on phase change materials have enormous application potential in optical logic circuits and optical communication systems. Integration of all-optical switching devices with optical fibers is a promising approach for realizing practical applications in enabling the optical fiber to transmit and process signals simultaneously. We describe an all-fiber nonvolatile broadband optical switch using an all-optical method. We use a single optical pulse to modulate the phase change material deposited on the tapered fiber to achieve logical control of the transmitted light. The response time of our optical switch is 80â ns for SET and 200â ns for RESET. Our optical switches can operate in the C-band (1530-1565â nm). The optical switching contrast is 40%. Our approach paves the way for all-optical nonvolatile fiber optic communication.
ABSTRACT
This study aimed to evaluate the relationship between the daily dietary intake of riboflavin (DDIR) and impaired lung function associated with dibutyl phthalate (DBP) exposure. Data of 4631 adults in this national cross-sectional survey were included. Urinary mono-benzyl phthalate (MBP) was used to evaluate the level of DBP exposure. The ln-transformed urinary creatinine-corrected MBP (ln(MBP/UCr)) level was used in the statistical models. High DDIR was defined as the DDIR ≥1.8 mg per day. The results of lung function impairment and high monocytes were significantly higher in the highest MBP group compared with the lowest MBP group. A significant interaction between ln(MBP/UCr) and DDIR (Pinteraction = 0.029) was detected for the risk of lung function impairment. The risk of lung function impairment (ORquartiles4 vs. 1 1.85, 95% CI, 1.27-2.71; Ptrend = 0.018) and high neutrophils (ORquartiles4 vs. 1 1.45, 95% CI, 1.06-1.97; Ptrend = 0.018) was significantly higher in the highest vs. the lowest quartile of MBP in participants with low/normal DDIR but not in in participants with high DDIR. The results of this study showed that high DDIR was associated with less lung function impairment related with DBP exposure, and the inhibiting of the neutrophil recruitment might be the potential mechanism.
Subject(s)
Dibutyl Phthalate , Eating , Adult , Cross-Sectional Studies , Dibutyl Phthalate/toxicity , Dibutyl Phthalate/urine , Humans , Lung , RiboflavinABSTRACT
High internal phase emulsions (HIPEs), also called highly concentrated emulsions with a minimal internal phase volume fraction of 74%, have been paid increasing attention in the development of functional foods due to their high potential in loading with large amounts of hydrophobic nutriceuticals. In the present study, HIPEs stabilized by polyphenol-amyloid supramolecular filaments were prepared for encapsulation of olive oil and loading with lutein. Binding and stacking of the green tea polyphenol epigallocatechin gallate (EGCG) on the surface of amyloid fibrils fabricated from hen egg lysozyme resulted in the hybrid supramolecules, which assembled to form hydrogels. The amyloid fibril clusters shrouded by EGCG were observed in the microstructure of the hydrogels characterized by atomic force microscopy (AFM). HIPEs stabilized by the EGCG-amyloid fibril supramolecules showed the typical microstructure of highly packed polyhedral geometric oil droplets. The gel strength of the HIPEs stabilized by the hybrid supramolecules was greater than that of HIPEs stabilized by pure amyloid fibrils. The droplet size of the HIPEs first decreased and then increased with the increase of EGCG contents in the hybrid supramolecules, which was consistent with the corresponding emulsion morphologies obtained from the images of confocal laser scanning microscopy (CLSM). Aggregation of the protein-based nanofibrils appeared in the continuous phase at higher EGCG contents. The droplet size of the HIPEs decreased with the increase of the amyloid fibril concentration, accompanied by more packed and homogenously dispersed lipid droplets, as shown in the CLSM images. A high loading content of lutein of up to 10 mg/mL in the prepared HIPEs was realized, and the stability of lutein against ultraviolet irradiation, heat, iron, and hydrogen peroxide was promoted significantly. In addition, encapsulation with the HIPEs prevented the oxidization of olive oil, and this effect was enhanced with the increase of the EGCG content in the hybrid supramolecules ranging from 0 to 0.25 wt %. The protection function of the HIPEs might be ascribed to the membrane of interfacial amyloid fibrils and the crowded oil droplet environment, both of which could shield the pro-oxidation factors.
Subject(s)
Amyloid , Polyphenols , Amyloid/chemistry , Emulsions/chemistry , Hydrogels , Lutein , Particle SizeABSTRACT
Selective neuronal accumulation of misfolded proteins is a key step toward neurodegeneration in a wide range of neurodegenerative diseases, including Huntington's (HD) diseases. Our recent studies suggest that Hsp70-binding protein 1 (HspBP1), an Hsp70/CHIP inhibitor that reduces protein folding, is highly expressed in neuronal cells and accounts for the accumulation of the HD protein huntingtin (HTT) in neuronal cells. To further determine the role of HspBP1 in regulation of mutant protein accumulation, we investigated whether increasing expression of HspBP1 in glial cells can also induce the accumulation of endogenous mutant HTT in glial cells and yield non-cell-autonomous toxic effects. We performed stereotaxic injection of AAV to selectively express HspBP1 in astrocytes in the brains of HD140Q knock-in (KI) mice that express mutant HTT ubiquitously but do not display obvious neurodegeneration. However, HspBP1 expression in HD140Q astrocytes led to the increased accumulation of endogenous mutant HTT and robust neuronal loss in the striatum of HD140Q KI mice. In transgenic HD mice that selectively express mutant HTT in astrocytes, increased accumulation of mutant HTT in astrocytes via HspBP1 expression did not elicit neurodegeneration but could exacerbate neurological symptoms. Consistently, suppressing the expression of endogenous HspBp1 in the striatum of HD140Q KI mice via CRISPR/Cas9 led to a significant reduction of mutant HTT accumulation. Our findings suggest that although endogenous mutant HTT in astrocytes can exacerbate neurological symptoms, it mediates neurodegeneration only when mutant HTT is also accumulated in neuronal cells.
Subject(s)
Astrocytes/metabolism , Huntingtin Protein/genetics , Huntingtin Protein/metabolism , Huntington Disease/genetics , Huntington Disease/metabolism , Mutation/physiology , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , Animals , Astrocytes/pathology , Cells, Cultured , Female , Huntington Disease/pathology , Male , Mice , Mice, Inbred C57BL , Mice, TransgenicABSTRACT
Huntington disease (HD) is an ideal model for investigating selective neurodegeneration, as expanded polyQ repeats in the ubiquitously expressed huntingtin (HTT) cause the preferential neurodegeneration in the striatum of the HD patient brains. Here we report that adeno-associated virus (AAV) transduction-mediated depletion of Hap1, the first identified huntingtin-associated protein, in adult HD knock-in (KI) mouse brains leads to selective neuronal loss in the striatum. Further, Hap1 depletion-mediated neuronal loss via AAV transduction requires the presence of mutant HTT. Rhes, a GTPase that is enriched in the striatum and sumoylates mutant HTT to mediate neurotoxicity, binds more N-terminal HTT when Hap1 is deficient. Consistently, more soluble and sumoylated N-terminal HTT is presented in HD KI mouse striatum when HAP1 is absent. Our findings suggest that both Rhes and Hap1 as well as cellular stress contribute to the preferential neurodegeneration in HD, highlighting the involvement of multiple factors in selective neurodegeneration.
Subject(s)
Corpus Striatum/pathology , Huntington Disease/metabolism , Nerve Tissue Proteins/metabolism , Neurons/physiology , Optogenetics , Animals , Corpus Striatum/metabolism , Dependovirus , Gene Expression Regulation , Huntington Disease/genetics , Lasers , Light , Mice , Nerve Net , Nerve Tissue Proteins/geneticsABSTRACT
OBJECTIVE: This study aimed to develop and validate a simple-to-use nomogram for predicting refractory Mycoplasma pneumoniae pneumonia (RMPP) in children. METHODS: A total of 73 children with RMPP and 146 children with general Mycoplasma pneumoniae pneumonia were included. Clinical, laboratory, and radiological data were obtained. A least absolute shrinkage and selection operator (LASSO) regression model was used to determine optimal predictors. The nomogram was plotted by multivariable logistic regression. The performance of the nomogram was assessed by calibration, discrimination, and clinical utility. RESULTS: The LASSO regression analysis identified lactate dehydrogenase, albumin, neutrophil ratio, and high fever as significant predictors of RMPP. This nomogram-illustrated model showed good discrimination, calibration, and clinical value. The area under the receiver operating characteristic curve of the nomogram was 0.884 (95% CI, 0.823-0.945) in the training set and 0.881 (95% CI, 0.807-0.955) in the validating set. Calibration curve and Hosmer-Lemeshow test showed good consistency between the predictions of the nomogram and the actual observations, and decision curve analysis showed that the nomogram was clinically useful. CONCLUSION: A simple-to-use nomogram for predicting RMPP in early stage was developed and validated. This may help physicians recognize RMPP earlier.
Subject(s)
Mycoplasma pneumoniae , Nomograms , Pneumonia, Mycoplasma/diagnosis , Child , Decision Support Techniques , Female , Humans , L-Lactate Dehydrogenase , Logistic Models , Male , Neutrophils , ROC CurveABSTRACT
Spinocerebellar ataxias 17 (SCA17) is caused by polyglutamine (polyQ) expansion in the TATA box-binding protein (TBP). The selective neurodegeneration in the cerebellum in SCA17 raises the question of why ubiquitously expressed polyQ proteins can cause neurodegeneration in distinct brain regions in different polyQ diseases. By expressing mutant TBP in different brain regions in adult wild-type mice via stereotaxic injection of adeno-associated virus, we found that adult cerebellar neurons are particularly vulnerable to mutant TBP. In SCA17 knock-in mice, mutant TBP inhibits SP1-mediated gene transcription to down-regulate INPP5A, a protein that is highly abundant in the cerebellum. CRISPR/Cas9-mediated deletion of Inpp5a in the cerebellum of wild-type mice leads to Purkinje cell degeneration, and Inpp5a overexpression decreases inositol 1,4,5-trisphosphate (IP3) levels and ameliorates Purkinje cell degeneration in SCA17 knock-in mice. Our findings demonstrate the important contribution of a tissue-specific protein to the polyQ protein-mediated selective neuropathology.
Subject(s)
Inositol Polyphosphate 5-Phosphatases/genetics , Purkinje Cells/pathology , Spinocerebellar Ataxias/pathology , TATA-Box Binding Protein/genetics , Animals , Disease Models, Animal , Down-Regulation , Gene Knock-In Techniques , HEK293 Cells , Humans , Inositol 1,4,5-Trisphosphate/metabolism , Inositol Polyphosphate 5-Phosphatases/metabolism , Mice , Mice, Transgenic , Peptides/genetics , Peptides/metabolism , Purkinje Cells/metabolism , Sp1 Transcription Factor/metabolism , Spinocerebellar Ataxias/genetics , TATA-Box Binding Protein/metabolism , Trinucleotide Repeat ExpansionABSTRACT
Calpains are a group of calcium-dependent proteases that are over activated by increased intracellular calcium levels under pathological conditions. A wide range of substrates that regulate necrotic, apoptotic and autophagic pathways are affected by calpain. Calpain plays a very important role in neuronal death and various neurological disorders. This review introduces recent research progress related to the regulatory mechanisms of calpain in neuronal death. Various neuronal programmed death pathways including apoptosis, autophagy and regulated necrosis can be divided into receptor interacting protein-dependent necroptosis, mitochondrial permeability transition-dependent necrosis, pyroptosis and poly (ADP-ribose) polymerase 1-mediated parthanatos. Calpains cleave series of key substrates that may lead to cell death or participate in cell death. Regarding the investigation of calpain-mediated programed cell death, it is necessary to identify specific inhibitors that inhibit calpain mediated neuronal death and nervous system diseases.
ABSTRACT
BACKGROUND: Metabolic syndrome (MS) is a disease with complex pathophysiology and pathogenesis involving multiple systems of the human body. This study aimed to identify serum metabolites that are relevant to MS. MATERIAL AND METHODS: This study involved 40 patients with MS and 28 healthy adults, and the following data were statistically analyzed: basic clinical data, blood lipids, fasting blood glucose, blood pressure, waist circumference, and visceral fat coefficient. Serum samples from both groups were collected and analyzed by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS); multivariate and univariate statistical methods were used to identify potential MS biomarkers and MS-related metabolic pathways. In addition, leucine and valine levels in serum from MS patients and normal subjects were measured using enzyme-linked immunosorbent assays (ELISAs). RESULTS: In this study, 23 potential biomarkers were identified in the plasma of MS patients. These biomarkers were mainly related to metabolism; the tricarboxylic acid cycle; galactose metabolism; arachidonic acid metabolism; valine, leucine, and isoleucine degradation; and valine, leucine, and isoleucine biosynthesis. ELISAs were utilized to verify serum leucine and valine levels, and the results supported the experimental metabolomics results. CONCLUSIONS: In total, 23 MS-related metabolites were identified in the serum; these differential metabolites were mainly associated with lipid metabolism, amino acid metabolism, glucose metabolism, purine metabolism, and other related metabolic pathways. This study shows that LC/MS-based metabolomics methods can be used to investigate the pathological changes in MS patients and identify biomarkers for the early diagnosis of MS.
Subject(s)
Biomarkers/blood , Mass Spectrometry/methods , Metabolic Networks and Pathways , Metabolic Syndrome/diagnosis , Metabolomics/methods , Adult , Aged , Biomarkers/analysis , Blood Chemical Analysis/methods , Case-Control Studies , Chromatography, Liquid , Female , Humans , Male , Metabolic Networks and Pathways/physiology , Metabolic Syndrome/blood , Metabolic Syndrome/epidemiology , Middle Aged , Principal Component AnalysisABSTRACT
BACKGROUND: Glaucoma mainly induced by increased intraocular pressure (IOP), it was believed that the pressure that wall of eyeball withstands were determined by material properties of the tissue and stereoscopic geometry of the eyeball. In order to study the pressure changes in different parts of interior eyeball wall, it is necessary to develop a novel eye ball FEM with more accurate geometry and material properties. Use this model to study the stress changes in different parts of eyeball, especially the lamina cribrosa (LC) under normal physiological and pathological IOP, and provide a mathematical model for biomechanical studies of selected retinal ganglion cells (RGCs) death. METHODS: (1) Sclera was cut into 3.8-mm wide, 14.5-mm long strips, and cornea was cut into 9.5-mm-wide and 10-mm-long strips; (2) 858 Mini BionixII biomechanical loading instrument was used to stretch sclera and cornea. The stretching rate for sclera was 0.3 mm/s, 3 mm/s, 30 mm/s, 300 mm/s; and for cornea were 0.3 mm/s and 30 mm/s. The deformation-stress curve was recorded; (3) Naso-temporal and longitudinal distance of LC were measured; (4) Micro-CT was used to accurately scan fresh bovine eyes and obtain the geometrical image and data to establish bovine eye model. 3-D reconstruction was performed using these images and data to work out the geometric shape of bovine eye; (5) IOP levels for eyeball FEM was set and the inner wall of eyeball was used taken as load-bearing part. Simulated eyeball FE modeling was run under the IOP level of 10 mmHg, 30 mmHg, 60 mmHg and 100 mmHg, and the force condition of different parts of eyeball was recorded under different IOP levels. RESULTS: (1) We obtained the material parameters more in line with physiological conditions and established a more realistic eyeball model using reversed engineering of parameters optimization method to calculate the complex nonlinear super-elastic and viscoelastic parameters more accurately; (2) We observed the following phenomenon by simulating increased pressure using FEM: as simulative IOP increased, the stress concentration scope on the posterior half of sclera became narrower; in the meantime, the stress-concentration scope on the anterior half of scleral gradually expanded, and the stress on the central part of LC is highest. CONCLUSION: As simulative IOP increased, stress-concentration scope on the posterior half of sclera gradually narrowed; in the meantime, the stress-concentration scope on the anterior half of sclera gradually expanded, and the stress on the LC is mainly concentrated in the central part, suggesting that IOP is mainly concentrated in the anterior part of the eyeball as it increases. This might provide a biomechanical evidence to explain why RGCs in peripheral part die earlier than RGCs in central part under HIOP.
Subject(s)
Cornea/physiology , Elasticity/physiology , Finite Element Analysis , Models, Theoretical , Sclera/physiology , Animals , Biomechanical Phenomena , Cattle , Glaucoma/physiopathology , Intraocular Pressure/physiology , Models, Biological , Optic Disk/physiology , Stress, MechanicalABSTRACT
PURPOSE: The aim of this study is to test the psychometric properties and acceptability of the European Organization for Research and Treatment of Cancer (EORTC) inpatient satisfaction with care questionnaire 32 (IN-PATSAT32) for evaluating Chinese cancer patients and to analyze the influence of age, educational level, diagnostic time, and tumor stage on patient satisfaction. METHODS: Three hundred two cancer inpatients in Tianjin Cancer Institution and Hospital from June 2013 to December 2013 were recruited for this study. All participants self-administered the EORTC IN-PATSAT32 and EORTC quality of life questionnaire-core 30 (QLQ-C30). Psychometric evaluation of the validity, reliability, acceptability, as well as the influence of age, educational level, diagnostic time, and tumor stage on patient satisfaction, was conducted. RESULTS: A favorable internal consistency reliability was confirmed, as the Cronbach's α coefficients were >0.80 for all scales in the EORTC IN-PATSAT32, ranging from 0.849 to 0.944. Multi-trait scaling analysis showed that all item-scale correlation coefficients met the standard of convergent validity, and 79.3 % met the standard of discriminant validity. Weak correlations were found between the scales and single items of the EORTC IN-PATSAT32 and EORTC QLQ-C30, proving the validity of EORTC IN-PATSAT32. None of the EORTC IN-PATSAT32 scales were able to discriminate between patients across age categories, while significant influences of educational level on doctors' and nurses' conduct, as well as influences of diagnostic time and tumor stage on nurses' conduct, and information provision scales were discovered. The questionnaire was easily understood with a satisfactory acceptability. CONCLUSIONS: The EORTC IN-PATSAT32 appears to be a reliable, valid, and acceptable instrument to use on cancer patients and is appropriate for measuring the patient satisfaction of Chinese patients.