Oleuropein enhances proteasomal activity and reduces mutant huntingtin-induced cytotoxicity.

Introduction: Huntington's disease (HD) is a hereditary neurodegenerative disorder that primarily affects the striatum, a brain region responsible for movement control. The disease is characterized by the mutant huntingtin (mHtt) proteins with an extended polyQ stretch, which are prone to aggregation. These mHtt aggregates accumulate in neurons and are the primary cause of the neuropathology associated with HD. To date, no effective cure for HD has been developed. Methods: The immortalized STHdh Q111/Q111 striatal cell line, the mHtt-transfected wild-type STHdh Q7/Q7 striatal cell line, and N2a cells were used as Huntington's disease cell models. Flow cytometry was used to assess cellular reactive oxygen species and transfection efficiency. The CCK-8 assay was used to measure cell viability, while fluorescence microscopy was used to quantify aggregates. Immunoblotting analyses were used to evaluate the effects on protein expression. Results: Polyphenols are natural antioxidants that offer neuroprotection in neurological disorders. In this study, we provide evidence that oleuropein, the primary polyphenol in olive leaves and olive oil, enhances cell viability in HD cell models, including. STHdh Q7/Q7 STHdh Q7/Q7 striatal cells, N2a cells ectopically expressing the truncated mHtt, and STHdh Q111/Q111 striatal cells expressing the full-length mHtt. Oleuropein effectively reduced both soluble and aggregated forms of mHtt protein in these HD model cells. Notably, the reduction of mHtt aggregates associated with oleuropein was linked to increased proteasome activity rather than changes in autophagic flux. Oleuropein seems to modulate proteasome activity through an unidentified pathway, as it did not affect the 20S proteasome catalytic ß subunits, the proteasome regulator PA28γ, or multiple MAPK pathways. Discussion: We demonstrated that oleuropein enhances the degradation of mHtt by increasing proteasomal protease activities and alleviates mHtt-induced cytotoxicity. Hence, we propose that oleuropein and potentially other polyphenols hold promise as a candidate for alleviating Huntington's disease.

Synergistic Effect of Thermoresponsive and Photocuring Methacrylated Chitosan-Based Hybrid Hydrogels for Medical Applications.

The thermoresponsive drug-loaded hydrogels have attracted widespread interest in the field of medical applications due to their ease of delivery to structurally complex tissue defects. However, drug-resistant infections remain a challenge, which has prompted the development of new non-antibiotic hydrogels. To this end, we prepared chitosan-methacrylate (CTSMA)/gelatin (GEL) thermoresponsive hydrogels and added natural phenolic compounds, including tannic acid, gallic acid, and pyrogallol, to improve the efficacy of hydrogels. This hybrid hydrogel imparted initial crosslinking at physiological temperature, followed by photocuring to further provide a mechanically robust structure. Rheological analysis, tensile strength, antibacterial activity against E. coli, S. aureus, P. gingivalis, and S. mutans, and L929 cytotoxicity were evaluated. The experimental results showed that the hybrid hydrogel with CTSMA/GEL ratio of 5/1 and tannic acid additive had a promising gelation temperature of about 37 °C. The presence of phenolic compounds not only significantly (p < 0.05) enhanced cell viability, but also increased the tensile strength of CTSMA/GEL hybrid hydrogels. Moreover, the hydrogel containing tannic acid revealed potent antibacterial efficacy against four microorganisms. It was concluded that the hybrid hydrogel containing tannic acid could be a potential composite material for medical applications.

Determination of structures, stabilities, and electronic properties for bimetallic cesium-doped gold clusters: a density functional theory study.

The equilibrium geometric structures, stabilities, and electronic properties of bimetallic Au(n)Cs (n = 1-10) and pure gold Au(n) (n ≤ 11) clusters have been systematically investigated by using density functional theory with meta-generalized gradient approximation. The optimized geometries show that one Au atom capped on Au(n-1)Cs structures and Cs atom capped Au(n) structures for different sized Au(n)Cs (n = 1-10) clusters are two dominant growth patterns. Theoretical calculated results indicate that the most stable isomers have three-dimensional structures at n = 4 and 6-10. Averaged atomic binding energies, fragmentation energies, and second-order difference of energies exhibit a pronounced even-odd alternations phenomenon. The same even-odd alternations are found in the highest occupied-lowest unoccupied molecular orbital gaps, vertical ionization potential, vertical electron affinity, and hardnesses. In addition, it is found that the charge in corresponding Au(n)Cs clusters transfers from the Cs atom to the Au(n) host in the range of 0.851-1.036 electrons.

Inhibition of p38 Mitogen-Activated Protein Kinase Ameliorates HAP40 Depletion-Induced Toxicity and Proteasomal Defect in Huntington's Disease Model.

Huntington's disease (HD) is a progressive neurodegenerative disorder caused by an expansion of polyglutamine stretch (polyQ) at the N-terminus of huntingtin (Htt) protein. The abnormally expanded polyQ stretch of mutant Htt makes it prone to aggregate, leading to neuropathology. HAP40 is a 40-kDa huntingtin-associated protein with undefined functions. HAP40 protein has been shown to increase in HD patients and HD mouse model cells. However, recent proteomic analysis provides new evidence that HAP40 protein is decreased in the striatum of HD knockin model mice. In this study, we developed HAP40-specific antibody and showed that both HAP40 mRNA and its encoded protein were reduced in HD striatal neuronal STHDHQ111/Q111 cells. Depletion of endogenous HAP40 led to cytotoxicity that was linked to increased accumulation of aggregated and soluble forms of mutant Htt, which recapitulates HD pathology. Moreover, we found that HAP40 depletion reduced the proteasomal chymotrypsin-like activity and increased the autophagic flux. Importantly, inhibition of p38 MAPK pathway by PD169316 increased chymotrypsin-like activity and reduced accumulation of aggregated and soluble forms of mutant Htt in HAP40-depleted cells to alleviate HAP40-depletion induced cytotoxicity. Taken together, our results suggest that modulation of p38 MAPK-mediated proteasomal peptidase activity may provide a new therapeutic target to restore proteostasis in neurodegenerative diseases.

Role of Organically-Modified Zn-Ti Layered Double Hydroxides in Poly(Butylene Succinate-Co-Adipate) Composites: Enhanced Material Properties and Photodegradation Protection.

In this research, the effects of Zn-Ti layered double hydroxide (Zn-Ti LDH) as a UV-protection additive, which was added to the poly(butylene succinate-co-adipate) (PBSA) matrix, were investigated. Stearic acid was used to increase the hydrophobicity of Zn-Ti LDH via ion-exchange method. Transmission electron microscopy images of PBSA composites showed that modified Zn-Ti LDH (m-LDH) well-dispersed in the polymer matrix. Due to the effect of heterogeneous nucleation, the crystallization temperature of the composite increased to 52.9 °C, and the accompanying crystallinity increased to 31.0% with the addition of 1 wt% m-LDH. The additional m-LDH into PBSA copolymer matrix significantly enhanced the storage modulus, as compared to pure PBSA. Gel permeation chromatography and Fourier transform infrared spectroscopy analysis confirmed that the addition of m-LDH can reduce the photodegradation of PBSA.

Synthesis, Physical Properties and Enzymatic Degradation of Biodegradable Nanocomposites Fabricated Using Poly(Butylene Carbonate-Co-Terephthalate) and Organically Modified Layered Zinc Phenylphosphonate.

A new biodegradable aliphatic-aromatic poly (butylene carbonate-co-terephthalate) (PBCT-85) with the molar ratio [BC]/[BT] = 85/15, successfully synthesized through transesterification and polycondensation processes, was identified using 1H-NMR spectra. Various weight ratios of PBCT/organically modified layered zinc phenylphosphonate (m-PPZn) nanocomposites were manufactured using the solution mixing process. Wide-angle X-ray diffraction and transmission electron microscopy were used to examine the morphology of PBCT-85/m-PPZn nanocomposites. Both results exhibited that the stacking layers of m-PPZn were intercalated into the PBCT-85 polymer matrix. The additional m-PPZn into PBCT-85 copolymer matrix significantly enhanced the storage modulus at -70 °C, as compared to that of neat PBCT-85. The lipase from Pseudomonas sp. was used to investigate the enzymatic degradation of PBCT-85/m-PPZn nanocomposites. The weight loss decreased as the loading of m-PPZn increased, indicating that the existence of m-PPZn inhibits the degradation of the PBCT-85 copolymers. This result might be attributed to the higher degree of contact angle for PBCT-85/m-PPZn nanocomposites. The PBCT-85/m-PPZn composites approved by MTT assay are appropriate for cell growth and might have potential in the application of biomedical materials.

Enhanced Photodegradation Stability in Poly(butylene adipate-co-terephthalate) Composites Using Organically Modified Layered Zinc Phenylphosphonate.

The enhancement of the ultraviolet (UV) photodegradation resistance of biodegradable polymers can improve their application efficacy in a natural environment. In this study, the hexadecylamine modified layered zinc phenylphosphonate (m-PPZn) was used as a UV protection additive for poly(butylene adipate-co-terephthalate) (PBAT) via solution mixing. The results from the Fourier transform infrared spectroscopy (FTIR) and wide-angle X-ray diffraction analysis of the m-PPZn indicated the occurrence of hexadecylamine intercalation. FTIR and gel permeation chromatography were used to characterize the evolution of the PBAT/m-PPZn composites after being artificially irradiated via a light source. The various functional groups produced via photodegradation were analyzed to illustrate the enhanced UV protection ability of m-PPZn in the composite materials. From the appearance, the yellowness index of the PBAT/m-PPZn composite materials was significantly lower than that of the pure PBAT matrix due to photodegradation. These results were confirmed by the molecular weight reduction in PBAT with increasing m-PPZn content, possibly due to the UV photon energy reflection by the m-PPZn. This study presents a novel approach of improving the UV photodegradation of a biodegradable polymer using an organically modified layered zinc phenylphosphonate composite.

Enzymatic Degradation of Acrylic Acid-Grafted Poly(butylene succinate-co-terephthalate) Nanocomposites Fabricated Using Heat Pressing and Freeze-Drying Techniques.

Biodegradable acrylic acid-grafted poly(butylene succinate-co-terephthalate) (g-PBST)/organically modified layered zinc phenylphosphonate (m-PPZn) nanocomposites were effectively fabricated containing covalent bonds between the g-PBST and m-PPZn. The results of wide-angle X-ray diffraction and transmission electron microscopy revealed that the morphology of the g-PBST/m-PPZn nanocomposites contained a mixture of partially exfoliated or intercalated conformations. The isothermal crystallization behavior of the nanocomposites showed that the half-time for crystallization of 5 wt % g-PBST/m-PPZn nanocomposites was less than 1 wt % g-PBST/m-PPZn nanocomposites. This finding reveals that increasing the loading of m-PPZn can increase the crystallization rate of nanocomposites. Degradation tests of g-PBST/m-PPZn nanocomposites fabricated using the heat pressing and the freeze-drying process were performed by lipase from Pseudomonas sp. The degradation rates of g-PBST-50/m-PPZn nanocomposites were significantly lower than those of g-PBST-70/m-PPZn nanocomposites. The g-PBST-50 degraded more slowly due to the higher quantity of aromatic group and increased stiffness of the polymer backbone. The degradation rate of the freeze-drying specimens contained a more extremely porous conformation compared to those fabricated using the heat pressing process.

Effects of melatonin on learning and memory abilities of fluoride-exposed offspring rats / 中华地方病学杂志

Objective:To investigate the effect of melatonin (MEL) on learning and memory abilities of fluoride-exposed offspring rats and the role of gut microbiota.Methods:Twelve 8-week-old Sprague-Dawley (SD) rats (8 females and 4 males) with a body weight ranging from 180 to 220 g were selected and divided into control group 1 and fluoride-exposed group 1 using a random number table method, with 6 rats in each group (female ∶ male = 2 ∶ 1). They were free to drink purified water or purified water containing 100 mg/L sodium fluoride, respectively. After 2 months, male and female rats were raised together in cages, and the first postnatal day (PND) of the offspring rats was recorded as PND0. In PND21, the offspring rats of fluoride-exposed group 1 were divided into fluoride-exposed group (Group F, n = 6) and fluoride + MEL group (Group FM, n = 6) using a group design, and continued to be exposed to fluoride through drinking water. The offspring rats of control group 1 were divided into control group (Group C, n = 6) and MEL group ( n = 6). The groups FM and MEL were given 20 mg/kg MEL by gavage, while the groups C and F were given the same dose of normal saline by gavage. In PND60, novel object recognition and Morris water maze tests were used to observe the learning and memory abilities of the offspring rats. Western blotting (WB) was used to detect the expression level of brain derived neurotrophic factor (BDNF) in the hippocampus of the offspring rats. And 16S rDNA sequencing technology was used to detect the changes in the structure and composition of gut microbiota in fecal samples. Results:The results of novel object recognition test showed that there was a statistically significant difference in the discrimination index (DI) among the four groups of offspring rats ( F = 3.95, P = 0.024). The DI in groups C and FM was higher than that of Group F ( P < 0.05). The results of Morris water maze test showed that compared with Group C, the platform-crossing time of the offspring rats of Group F were less and they had a longer time to reach the platform for the first time ( P < 0.05). Compared with Group F, the platform-crossing time of the offspring rats of Group FM were increased and they had a shorter time to reach the platform for the first time ( P < 0.05). The WB results showed that compared with Group C (1.00 ± 0.07), the expression level of BDNF protein in Group F (0.68 ± 0.26) was lower ( P < 0.05). Compared with Group F, the expression level of BDNF protein in Group FM (0.99 ± 0.14) was higher ( P < 0.05). Anosim similarity analysis showed significant differences in the structure and composition of gut microbiota in the four groups of offspring rats ( R = 0.395 062, P = 0.002). The distribution characteristics of gut microbiota species showed that at the phylum level, compared with Group C, the relative abundance of Bacteroidetes in Group F increased from 14.26% to 37.00%, and the relative abundance of Firmicutes decreased from 68.78% to 45.95%. Compared with Group F, the relative abundance of Firmicutes in Group FM increased from 45.95% to 65.26%, and the relative abundance of Bacteroidetes decreased from 37.00% to 23.00%. At the genus level, compared with Group C, the relative abundance of Lactobacillus, Dubosiella, HT002 and UCG-005 in Group F was lower, while the relative abundance of unclassified Muribaculaceae was higher. Compared with Group F, the relative abundance of Lactobacillus, Dubosiella, HT002 and UCG-005 in Group FM was higher, while the relative abundance of unclassified Muribaculaceae was lower. The results of linear discriminant analysis revealed that the Candidatus-Saccharimonas and Incertae-Sedis were significantly enriched in Group C, unclassified Muribaculaceae and Muribaculum were significantly enriched in Group F, and Allorhizobium- Neorhizobium- Pararhizobium- Rhizobium were significantly enriched in Group FM. Conclusion:MEL can improve the learning and memory impairment of offspring rats induced by fluoride exposure by changing the structure and composition of gut microbiota.

Relationship between atherogenic index of plasma and childhood asthma / 中国当代儿科杂志

OBJECTIVES@#To explore the relationship between atherogenic index of plasma (AIP) and childhood asthma.@*METHODS@#This retrospective study included 86 children with asthma admitted to the Changzhou Second People's Hospital Affiliated to Nanjing Medical University from July 2020 to August 2022 as the asthma group and 149 healthy children undergoing physical examination during the same period as the control group. Metabolic parameters including total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and blood glucose, as well as general information of the children such as height, weight, body mass index, presence of specific dermatitis, history of inhalant allergen hypersensitivity, family history of asthma, and feeding history, were collected. Multivariable logistic regression analysis was used to study the relationship between AIP, triglycerides, and high-density lipoprotein cholesterol and asthma. The value of AIP, triglycerides, and high-density lipoprotein cholesterol for predicting asthma was assessed using receiver operating characteristic (ROC) curve analysis.@*RESULTS@#The AIP and triglyceride levels in the asthma group were significantly higher than those in the control group, while high-density lipoprotein cholesterol was significantly lower (P<0.05). However, there was no significant difference in total cholesterol and low-density lipoprotein cholesterol between the two groups (P>0.05). Before and after adjusting for height, weight, presence of specific dermatitis, history of inhalant allergen hypersensitivity, family history of asthma, feeding method, and blood glucose, multivariable logistic regression analysis showed that AIP, triglycerides, and high-density lipoprotein cholesterol were associated with asthma (P<0.05). ROC curve analysis showed that the optimal cutoff value for predicting asthma with AIP was -0.333, with a sensitivity of 80.2%, specificity of 55.0%, positive predictive value of 50.71%, and negative predictive value of 82.85%. The area under the curve (AUC) for AIP in predicting asthma was significantly higher than that for triglycerides (P=0.009), but there was no significant difference in AUC between AIP and high-density lipoprotein cholesterol (P=0.686).@*CONCLUSIONS@#AIP, triglycerides, and high-density lipoprotein cholesterol are all associated with asthma. AIP has a higher value for predicting asthma than triglycerides and comparable value to high-density lipoprotein cholesterol.

Detection of Toxoplasma gondii Infections using Virus-Like Particles Displaying T. gondii ROP4 Antigen

Toxoplasma gondii ME49 infections are typically diagnosed by serological tests. However, serological diagnosis of RH strain-induced toxoplasmosis remains unknown. In order to develop seradiagnosis of above 2 kinds of infections, we generated recombinant virus-like particles (VLPs) displaying the T. gondii rhoptry protein 4 (ROP4) and evaluated their potential in T. gondii ME49 or RH strain infection diagnostics. Mice were orally infected with either the tachyzoites of T. gondii (RH) or cysts of T. gondii (ME49) at various dosages, and sera were collected at regular intervals. ELISA-based serological tests were performed to assess IgG, IgM, and IgA antibody responses against ROP4 VLP antigen and tissue lysate antigen (TLA). Compared to TLA, IgG, IgM, and IgA levels to ROP4 VLP antigen were significantly higher in the sera of T. gondii RH-infected mice 1 and 2 week post-infection (PI). T. gondii-specific IgG antibody was detected at 1, 2, 4, and 8 week PI in the T. gondii ME49-infected mice with infection dose-dependent manner. These results indicated that the ROP4 VLP antigen was highly sensitive antigens detecting T. gondii RH and ME49 antibodies at an early stage.

Nucleosides from Acorus tatarinowii and Their Transformation Pathway / 中国实验方剂学杂志

Objective:To study the water soluble chemical constituents in rhizoma of Acorus tatarinowii and transformation pathway of nucleosides in the process of water extraction. Method:Compounds were isolated and purified by column chromatography on macroporous resin，Sephadex LH-20，ODS and preparative HPLC. Their structures were identified on the basis of physicochemical properties and spectral data. Nucleosides were identified from aqueous extract of A. tatarinowii，and their stability was investigated by HPLC. The possible transformation pathways of nucleosides in aqueous extract of A. tatarinowii were studied by nucleotide addition test. Result:Eleven compounds including four nucleosides，four phenylpropanoids，two alkaloids and a furfural were isolated，and identified as uridine（1），adenine（2），guanosine（3），adenosine（4），5-hydroxymethylfurfural（5），5-（hydroxymethyl）-1H-pyrrole-2-carboxaldehyde（6），（threo）1'，2'-dihydroxyasarone（7），（erythro）1'，2'-dihydroxyasarone（8），acoraminol A（9），acoraminol B（10），and tatarine A（11）. The chromatographic peaks of compounds 1-4 and cytidine were identified from aqueous extract of A. tatarinowii by HPLC. After ultrasonic extraction for 0.5 h，the stability of nucleosides in water was poor. After ultrasonic extraction for 3 h or refluxing extraction for 0.5 h，the stability of nucleosides in water was good. Four transformation pathways including 5'-cytidylic acid→cytidine，uridine monophosphate→uridine，guanosine monophosphate，guanosine and adenosine-5'-monophosphate，adenosine 5'-diphosphate，adenosine 5'-triphosphorate，adenosine，adenine might exist in water extract of A. tatarinowii. Conclusion:Compounds 1-4 and 6 were isolated from the genus Acorus for the first time. These compounds further enriched the chemical constituents of A. tatarinowii. The stability and transformation pathway of nucleosides in A. tatarinowii provides reference data for the analysis of nucleosides in A. tatarinowii and other traditional Chinese medicine.

Fatigue correlates with sleep disturbances in Parkinson disease / 中华医学杂志(英文版)

BACKGROUND@#Many Parkinson disease (PD) patients complain about chronic fatigue and sleep disturbances during the night. The objective of this study is to determine the relationship between fatigue and sleep disturbances by using polysomnography (PSG) in PD patients.@*METHODS@#Two hundred and thirty-two PD patients (152 with mild fatigue and 80 with severe fatigue) were recruited in this study. Demographic information and clinical symptoms were collected. Fatigue severity scale (FSS) was applied to evaluate the severity of fatigue, and PSG was conducted in all PD patients. FSS ≥4 was defined as severe fatigue, and FSS <4 was defined as mild fatigue. Multivariate logistic regression and linear regression models were used to investigate the associations between fatigue and sleep disturbances.@*RESULTS@#Patients with severe fatigue tended to have a longer duration of disease, higher Unified Parkinson Disease Rating Scale score, more advanced Hoehn and Yahr stage, higher daily levodopa equivalent dose, worse depression, anxiety, and higher daytime sleepiness score. In addition, they had lower percentage of rapid eye movement (REM) sleep (P = 0.009) and were more likely to have REM sleep behavior disorder (RBD) (P = 0.018). Multivariate logistic regression analyses found that the presence of RBD and proportion of REM sleep were the independent predictors for fatigue. After the adjustment of age, sex, duration, body mass index, severity of disease, scores of Hamilton Rating Scale for Depression, Hamilton Anxiety Rating Scale, and other sleep disorders, proportion of REM sleep and degree of REM sleep without atonia in patients with PD were still associated with FSS score.@*CONCLUSION@#Considering the association between fatigue, RBD, and the altered sleep architecture, fatigue is a special subtype in PD and more studies should be focused on this debilitating symptom.

Scientificity of traditional commodity grade of Chinese medicinal materials--taking Lonicerae Japonicae Flos as example / 中国中药杂志

Taking Lonicerae Japonicae Flos as an example, the method of "expert consensus of different regions" was used to screen the representative samples and evaluate their commodity grades. The correlation analysis, hierarchical cluster analysis and partial least squares discriminant analysis(PLS-DA) of "commodity grade-appearance characteristic-component content" were carried out to reveal the scientificity of traditional commodity grade of Chinese medicinal material. By referring to the existing literature and the grade investigation from the sample collection regions, 78 "initial grade" samples were screened out from 118 collected samples. Authoritative experts from four regions(n=4) including Linyi(Shangdong province), Bozhou(Anhui province), Anguo(Hebei province) and Beijing were organized to evaluate their commodity grades, separately. Based on the grade consistency rate(R_i≥70%), 69 "local grade" samples were screened out from the "initial grade" samples. Based on the average grade consistency rate ■ "authoritative grade" samples were screened out from the "local grade" samples, including15 first-grade samples, 9 second-grade samples, 11 third-grade samples and 17 fourth-grade samples. For these "authoritative grade" samples, the main appea-rance characteristics were quantified and the contents of 13 components were determined by ultra performance liquid chromatography(UPLC). Furthermore, the total contents of 6 phenolic acids, 4 flavonoids and 3 iridoids were calculated, respectively. The results of correlation analysis showed that 4 appearance characteristics indices were correlated with the commodity grades: color, rate of yellow bars(including blooming flowers), rate of black heads(including black bars), and rate of stems and leaves(including bud debris). Five component content indices were correlated with the commodity grades: chlorogenic acid, isochlorogenic acid C, sweroside, loganin and the total contents of six phenolic acids. Furthermore, chlorogenic acid, loganin and the total contents of six phenolic acids showed significantly negative correlation with the main appearance characteristics, indicating that the appearance characteristics of Lonicerae Japonicae Flos can reflect its internal quality, and these 3 indices can be used as quality markers(Q-markers). The results of hierarchical cluster analysis showed that the samples of four grades were classified into four categories, and the samples with the same grades and the same categories accounted for 80.8% of the total samples, while the samples with the different grades were obviously classified into different categories. The results of PLS-DA analysis showed that the samples of different grades showed obvious intragroup aggregation and intergroup dispersion. The above results indicated that it was feasible to evaluate the traditional commodity grade of Lonicerae Japonicae Flos by the method of "expert consensus of different regions". For the evaluation of traditional commodity grade of Chinese medicinal material, the samples should be representative, expert conclusions should have enough consensuses, and grade determination should be authoritative. As the crystallization of clinical experience, traditional commodity grade can scientifically reflect the internal quality of Chinese medicinal material.

Theory of wave propagation along a waveguide filled with moving magnetized plasma.

Making use of the transformation of constitutive relations for electromagnetic waves and the transformation of the wave vector in Minkowski space, we have worked out the theory of wave propagation along a waveguide filled with moving magnetized plasma (MMPW). The dispersion equations of the wave propagation in a circular MMPW are given in this paper, along with a detailed discussion of their behaviors. Numerical calculations show that there are many interesting and important features of the wave propagation along an MMPW compared with that in a stationary magnetized plasma-filled waveguide (MPW).

Pros and cons of the tuberculosis drugome approach--an empirical analysis.

Drug-resistant Mycobacterium tuberculosis (MTB), the causative pathogen of tuberculosis (TB), has become a serious threat to global public health. Yet the development of novel drugs against MTB has been lagging. One potentially powerful approach to drug development is computation-aided repositioning of current drugs. However, the effectiveness of this approach has rarely been examined. Here we select the "TB drugome" approach--a protein structure-based method for drug repositioning for tuberculosis treatment--to (1) experimentally validate the efficacy of the identified drug candidates for inhibiting MTB growth, and (2) computationally examine how consistently drug candidates are prioritized, considering changes in input data. Twenty three drugs in the TB drugome were tested. Of them, only two drugs (tamoxifen and 4-hydroxytamoxifen) effectively suppressed MTB growth at relatively high concentrations. Both drugs significantly enhanced the inhibitory effects of three first-line anti-TB drugs (rifampin, isoniazid, and ethambutol). However, tamoxifen is not a top-listed drug in the TB drugome, and 4-hydroxytamoxifen is not approved for use in humans. Computational re-examination of the TB drugome indicated that the rankings were subject to technical and data-related biases. Thus, although our results support the effectiveness of the TB drugome approach for identifying drugs that can potentially be repositioned for stand-alone applications or for combination treatments for TB, the approach requires further refinements via incorporation of additional biological information. Our findings can also be extended to other structure-based drug repositioning methods.

Plasma Macrophage Migration Inhibitory Factor and CCL3 as Potential Biomarkers for Distinguishing Patients with Nasopharyngeal Carcinoma from High-Risk Individuals Who Have Positive Epstein-Barr Virus Capsid Antigen-Specific IgA / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to identify novel plasma biomarkers for distinguishing nasopharyngeal carcinoma (NPC) patients from healthy individuals who have positive Epstein-Barr virus (EBV) viral capsid antigen (VCA-IgA). MATERIALS AND METHODS: One hundred seventy-four plasma cytokines were analyzed by a Cytokine Array in eight healthy individuals with positive EBV VCA-IgA and eight patients with NPC. Real-time polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry were employed to detect the expression levels of macrophage migration inhibitory factor (MIF) and CC chemokine ligand 3 (CCL3) in NPC cell lines and tumor tissues. Plasma MIF and CCL3 were measured by ELISA in 138 NPC patients, 127 EBV VCA-IgA negative (VN) and 100 EBV VCA-IgA positive healthy donors (VP). Plasma EBV VCA-IgA was determined by immunoenzymatic techniques. RESULTS: Thirty-four of the 174 cytokines varied significantly between the VP and NPC group. Plasma MIF and CCL3 were significantly elevated in NPC patients compared with VN and VP. Combination of MIF and CCL3 could be used for the differential diagnosis of NPC from VN cohort (area under the curve [AUC], 0.913; sensitivity, 90.00%; specificity, 80.30%), and combination of MIF, CCL3, and VCA-IgA could be used for the differential diagnosis of NPC from VP cohort (AUC, 0.920; sensitivity, 90.00%; specificity, 84.00%), from (VN+VP) cohort (AUC, 0.961; sensitivity, 90.00%; specificity, 92.00%). Overexpressions of MIF and CCL3 were observed in NPC plasma, NPC cell lines and NPC tissues. CONCLUSION: Plasma MIF, CCL3, and VCA-IgA combination significantly improves the diagnostic specificity of NPC in high-risk individuals.

Clinical study on the Xingshen-Kaiqiao acupuncture combined with salviae miltiorrhizae and ligustrazine hydrochloride injection for acute cerebral infarction / 国际中医中药杂志

Objective To evaluate the efficacy of Xingshen-Kaiqiao combined with salviae miltiorrhizae and ligustrazine hydrochloride injection in the treatment of acute cerebral infarct (ACI). Methods A total of 142 patients with ACI meeting the inclusion criteria were randomly divided into 2 groups, with 71 cases in each group. The control group received intravenous injection of salviae miltiorrhizae and ligustrazine hydrochloride injection on the basis of routine treatment, and the observation group was given Xingshen-Kaiqiao acupuncture method on the basis of the control group. After treatment of ed with 14 days, the enzyme linked immunosorbent assay was used to detect the central nervous specific protein (S100γ) was detected by the enzyme linked immunosorbent assay, the level of homocysteine (Hcy) was detected by circulating enzyme method. T, the level of hypersensitive C-reactive protein (hs-CRP) was detected by immunization turbidimetry, and the automatic coagulant was used to detecded the D-Dimer (D-D) and antithrombin Ⅲ (AT Ⅲ) levels by the automatic coagulant. The degree of nerve function defect in patients were evaluated using the National Institute of Health Stroke Scale (NIHSS), and the daily living ability of the patients by the improved barthel index (MBI) were evaluated, and the clinical efficacy was also observed. Results The total effective rate of the observation group was 97.2％ (69/71), and the total effective rate of thecontrol group was 88.7％ (63/71), with the difference showing statistically significant (χ2=3.873, P=0.049). The score of 7 d (6.1 ± 1.9 vs. 8.2 ± 2.1, t=2.520), 14 d (3.8 ± 1.1 vs. 6.2 ± 1.8, t=2.712) of the observation group were significantly lower than that those of the control group (P<0.05); ). The MBI scores after 7 d and 14 d were respectively (77.7 ± 8.1 vs. 64.1 ± 7.1, t=2.803) and 14 d and (83.2 ± 9.1 vs. 76.5 ± 7.8, t=4.014) of the observation group were significantly higher than those of the control group (P<0.05); ). After the treatment, the D-D (0.79 ± 0.33 g/ml vs. 1.22 ± 0.37 g/ml, t=4.221), Hcy (13.46 ± 2.89 μmol/L vs. 18.33 ± 3.09 μmol/L, t=5.692), hs-CRP (12.85 ± 3.23 mg/L vs. 18.65 ± 4.13 mg/L t=5.279), the S100γ (91.63％ ± 5.06％ vs. 83.05％ ± 4.87％, t=6.086) of the observation group were significantly higher than those of the control group (P<0.01). Conclusions The combination of Xingshen-Kaiqiao acupuncture method and salviae miltiorrhizae and ligustrazine hydrochloride injection can improve the level of anticoagulant factor in the patients, and reduce the inflammatory response in the infarct area and promote the recovery of nerve.

Clinical application of probiotics and dietary fiber in the prevention of elderly with antibiotic associated diarrhea / 天津医药

Objective To investigate the clinical usefulness and safety of soluble dietary fiber (SDF) combined with probiotics in treating elderly patients with antibiotic associated diarrhea(AAD).Methods A total of 88 hospitalized elderly patients (≥65 years old) treated with antibiotics during August 2014 to August 2016 were included in this study. Patients were divided into control group(26 cases),probiotics group(30 cases)and combined group(32 cases).The control group was given maltodextrin as placebo intervention, the probiotics group was given the same dose of probiotics only, and the combined group was given SDF and probiotics treatment. The treatment was observed for 14 d. The incidence and the recurrence rate of ADD, the results of fecal culture and the incidence of adverse reactions were monitored in the three groups. Results The incidence of ADD was obviously lower in the combined group and the probiotics group than that of control group(6.25% vs.26.92%,6.67% vs.26.92%,P<0.05).The disease duration of diarrhea was shorter in the combined group than that of probiotic group[(3.53 ± 0.62)d vs.(4.39 ± 1.01)d,P<0.05],but no difference was found when compared with that of control group [(3.55 ± 0.65) d]. After 7-day intervention, Enterococcus counts was significantly deceased in probiotic group(P<0.05).There were no significant changes in Lactobacillus and Bifidobacterium counts in probiotic group after 14-day intervention. In the combined group, after 7-day intervention, Enterococcus counts decreased (P<0.05), and then started increasing until the 14-day(P<0.05).Lactobacillus and Bifidobacterium counts increased with the time passed (P<0.05).The incidence rates of total adverse reactions were 6.25%,10.00% and 23.07% for combined group,probiotics group and control group,and with no significant differences between them.Conclusion The probiotics combined with SDF has a good clinical effect on preventing the occurrence of antibiotic associated diarrhea and shortening the course of diarrhea in the elderly.It has high safety and it can regulate the intestinal flore with high safety.

Alpha-mangostin affects the proliferation and apoptosis of gastric cancer cells by increasing autophagy / 西安交通大学学报(医学版)

Objective To investigate the possible molecular mechanism for alpha(α)-mangostin's inhibition of the proliferation and apoptosis of human gastric cancer cells.Methods Human gastric adenocarcinoma SGC7901 cell line was treated with α-mangostin.CCK8 method was used to measure the viability of SGC7901 cells.The effect of α-mangostin on apoptosis and cell cycle was determined by immune fluorescence and flow cytometry.The expression of the relevant proteins was detected using Western blot.The shapiro-wilk test was performed for evaluation of deviation from normality.Normally distributed data was analyzed with one-way ANOVA.Welch test was used in data with heterogeneity of variance and multiple compared by Games-Howell test after that.Results CCK8 results showed that cell viability differed significantly among groups treated with different concentrations of α-mangostin(10,15,20,25,and 30 μmol/L)(P＜0.05).QPCR data showed that the concentration of α-mangostin was positively correlated with mRNA level of LC 3 but not caspase protein(r=0.976,P＜0.05).In 15 μmol/L but not 10 μmol/L α-mangostin treatment system,the autophagy inhibitors 3-MA(10 μmol/L),bafilomycin A(10 μmol/L)and LY294002(10 μmol/L)could significantly alleviate α-mangostin's killing effect on SGC7901 cells(P＜0.05).Conclusion The anti-tumor effects of α-mangostin against human gastric adenocarcinoma cells in vitro can be partly attributed to apoptosis,autophagy and arresting cell phase.