Identification of potential biomarkers of leprosy: A study based on GEO datasets.

Leprosy has a high rate of cripplehood and lacks available early effective diagnosis methods for prevention and treatment, thus novel effective molecule markers are urgently required. In this study, we conducted bioinformatics analysis with leprosy and normal samples acquired from the GEO database(GSE84893, GSE74481, GSE17763, GSE16844 and GSE443). Through WGCNA analysis, 85 hub genes were screened(GS > 0.7 and MM > 0.8). Through DEG analysis, 82 up-regulated and 3 down-regulated genes were screened(|Log2FC| > 3 and FDR < 0.05). Then 49 intersection genes were considered as crucial and subjected to GO annotation, KEGG pathway and PPI analysis to determine the biological significance in the pathogenesis of leprosy. Finally, we identified a gene-pathway network, suggesting ITK, CD48, IL2RG, CCR5, FGR, JAK3, STAT1, LCK, PTPRC, CXCR4 can be used as biomarkers and these genes are active in 6 immune system pathways, including Chemokine signaling pathway, Th1 and Th2 cell differentiation, Th17 cell differentiation, T cell receptor signaling pathway, Natural killer cell mediated cytotoxicity and Leukocyte transendothelial migration. We identified 10 crucial gene markers and related important pathways that acted as essential components in the etiology of leprosy. Our study provides potential targets for diagnostic biomarkers and therapy of leprosy.

Emodin attenuates inflammation and demyelination in experimental autoimmune encephalomyelitis.

Emodin, a substance extracted from herbs such as rhubarb, has a protective effect on the central nervous system. However, the potential therapeutic effect of emodin in the context of multiple sclerosis remains unknown. In this study, a rat model of experimental autoimmune encephalomyelitis was established by immune induction to simulate multiple sclerosis, and the rats were intraperitoneally injected with emodin (20 mg/kg/d) from the day of immune induction until they were sacrificed. In this model, the nucleotide-binding domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and the microglia exacerbated neuroinflammation, playing an important role in the development of multiple sclerosis. In addition, silent information regulator of transcription 1 (SIRT1)/peroxisome proliferator-activated receptor-alpha coactivator (PGC-1α) was found to inhibit activation of the NLRP3 inflammasome, and SIRT1 activation reduced disease severity in experimental autoimmune encephalomyelitis. Furthermore, treatment with emodin decreased body weight loss and neurobehavioral deficits, alleviated inflammatory cell infiltration and demyelination, reduced the expression of inflammatory cytokines, inhibited microglial aggregation and activation, decreased the levels of NLRP3 signaling pathway molecules, and increased the expression of SIRT1 and PGC-1α. These findings suggest that emodin improves the symptoms of experimental autoimmune encephalomyelitis, possibly through regulating the SIRT1/PGC-1α/NLRP3 signaling pathway and inhibiting microglial inflammation. These findings provide experimental evidence for treatment of multiple sclerosis with emodin, enlarging the scope of clinical application for emodin.

Genotype profiles of Helicobacter pylori from gastric biopsies and strains with antimicrobial-induced resistance.

BACKGROUND AND AIMS: The genotypic method could significantly shorten the time needed to obtain antibiotic susceptibility data for Helicobacter pylori. The aim of this study was to explore the profile of H. pylori from gastric biopsies and strains with antibiotic-induced resistance. METHODS: A total of 124 gastric biopsies were used to perform gene sequencing and to perform bacterial culture and susceptibility testing. Seven susceptible strains were selected to develop resistance to clarithromycin, levofloxacin, and metronidazole. Four susceptible strains were selected to transfer candidate mutations. The genotype profiles of these groups were analyzed by sequencing analysis. The antibiotic susceptibility of these strains was detected using the E-test method. RESULTS: Phenotypic resistance to clarithromycin, levofloxacin, and metronidazole was observed in 35.5%, 40.0%, and 79.8% strains, respectively. Point mutations in 23 S rRNA, gyrA, and rdxA genes were observed in 39.5%, 38.7%, and 86.3% of gastric biopsies, respectively. The A2143G mutation in the 23S rRNA occurs in most clarithromycin-resistant samples. The A2142C point mutation showed a higher efficacy than A2142G and A2143G for inducing clarithromycin resistance. The D91N and N87K mutations in gyrA occurs in most levofloxacin-resistant samples, and double point mutations showed a higher efficacy than single mutations for inducing levofloxacin resistance. Phenotypic resistance and mutations in rdxA lacked consistency. CONCLUSION: Genotype-based gastric biopsy analysis was reliable for determining clarithromycin and levofloxacin resistance. A2143G in 23S rRNA and N87K/D91N in the gyrA gene occurred in most resistant strains. Mutations in the rdxA gene were not good indicators of metronidazole resistance.

A Quantum secure sharing protocol for Cloud data based on proxy re-encryption.

A quantum scheme for cloud data sharing based on proxy re-encryption is proposed. The user Alice stores the cipher-text of her data on cloud data center. When Alice wants to share her data with another user Bob, Alice is called the delegator and Bob is called the delegatee. The cloud service provider (called the proxy) can convert the delegator's cipher-text into the delegatee's cipher-text without decrypting the former, so that the delegatee can get the plain-text of Alice's data with his private key. The proxy cannot obtain the plain-text of the user's data stored on cloud data center. Delegator in the protocol should have the ability of producing Bell states, performing Bell basis and Z-basis measurements, and storing qubits. The quantum requirements for the delegatee are reduced. The delegatee needs to have the ability of reflecting and performing Z-basis measurement. One secret at a time (one-time one-pad) is theoretically implemented, especially when the same data is shared multiple times. The anti-selection plain-text attack security and the anti-selective cipher-text attack security are realized. Fine-granularity secret data sharing is achieved flexibly.

[Preparation of angiopep-2-modified FITC-labeled neurotoxin nanoparticles and in vitro release characteristics].

In order to prepare angiopep-2 modified fluorescein isothiocyanate-labeled neurotoxin nanoparticles( ANG-NPs/FITCNT),emulsion/solvent evaporation method was used with m PEG-PLA and ANG-PEG-PLA( in proper proportions) as carriers and with FITC-NT as drug. With particle size and encapsulation efficiency as comprehensive indexes,the effects of different ultrasound power and ultrasound time combinations on the process were investigated. The in vitro release characteristics of nanoparticles in PBS buffer at p H 7. 4 and p H 6. 5 were investigated by dialysis method. The results indicated that the optimum process for preparing ANG-NPs/FITC-NT was as follows: ultrasonic power 90 W,ultrasonic time 30 s. In such optimal process,ANG-NPs/FITC-NT were well-shaped under the transmission electron microscope,with an average particle size of( 123. 9±0. 5) nm,Zeta potential of(-10. 5±0. 5) m V,encapsulation efficiency of( 68. 1±0. 4) %,and the drug loading of( 0. 82±0. 01) %. The in vitro drug release profiles of the nanoparticles in PBS buffer at p H 7. 4 and p H 6. 5 were both consistent with Ritger-Peppas equation,ln Q = 0. 508 8 lnt-2. 285 0,r = 0. 961 5( p H 7. 4) and ln Q= 0. 449 9 lnt-1. 855 3,r = 0. 970 3( p H 6. 5),respectively. The experiment results proved that the nanoparticles prepared by emulsion/solvent evaporation method had uniform particle size,high encapsulation efficiency and in vitro sustained release characteristic,which might be a potential carrier for NT intracerebral drug delivery.

Mesoproterozoic juvenile crust in microcontinents of the Central Asian Orogenic Belt: evidence from oxygen and hafnium isotopes in zircon.

We report in situ O and Hf isotope data of zircon grains from coeval Mesoproterozoic (ca. 1.4 Ga) igneous metamafic (amphibolite) and granitic rocks of the Chinese Central Tianshan microcontinent (CTM) in the southern Central Asian Orogenic Belt (CAOB). Zircon grains from amphibolite have mantle-like δ18OVSMOW values of 4.7-5.6‰ and juvenile Hf isotopic compositions (εHf(t) = 8.4-15.3; TDMC = 1.57-1.22 Ga), whereas those from granitic rocks have δ18OVSMOW values of 5.6-7.0‰ and evolved Hf isotopic compositions (εHf(t) = -1.0-8.2; TDMC = 2.09-1.62 Ga). Zircon O-Hf isotopic compositions of the metamafic and granitic rocks provide evidence for Mesoproterozoic (ca. 1.4 Ga) crustal growth and a substantial Palaeoproterozoic supracrustal component in the CTM. These findings and previous studies, reporting ca. 1.4 Ga magmatic rocks from other microcontinents of the CAOB, suggest that a large belt of Mesoproterozoic (ca. 1.4 Ga) juvenile continental crust formed in a continental terrane, fragments of which now occur over a distance of more than a thousand kilometres in the southern CAOB.

Dichloroacetate induces protective autophagy in esophageal squamous carcinoma cells.

Dichloroacetate (DCA) is an inhibitor of pyruvate dehydrogenase kinase, which promotes the flux of carbohydrates into mitochondria and enhances the aerobic oxidation of glucose. DCA has previously been demonstrated to exhibit antitumor properties. The present study revealed that treatment with DCA induced increased levels of autophagy-associated proteins in esophageal squamous carcinoma cells while minimally affecting apoptosis. The present study examined the localization of light chain (LC)-3 by adenovirus infection with a green fluorescent protein (FP)-red FP-LC3 reporter construction and confirmed that DCA treatment induced significant autophagy. Furthermore, the inhibition of DCA-induced autophagy facilitated cell apoptosis and improved the drug sensitivity of esophageal squamous carcinoma cells to DCA and 5-FU (5-fluorouracil). The proliferation of TE-1 cells was markedly inhibited at low concentrations of DCA and 5-FU treatment when subjected to Atg5 mRNA interference, indicating that autophagy performed a protective role in cell survival upon DCA treatment. To determine the underlying mechanism of DCA-induced autophagy, the present study measured alterations in autophagy-associated signaling pathways. Notably, the protein kinase B (Akt)-mechanistic target of rapamycin (mTOR) signaling pathway, an important negative regulator of autophagy, was demonstrated to be suppressed by DCA treatment. These results may direct the development of novel strategies for the treatment of esophageal squamous carcinoma based on the combined use of DCA and autophagy inhibitors.

Comparison of two different size needles in endoscopic ultrasound-guided fine-needle aspiration for diagnosing solid pancreatic lesions: A meta-analysis of prospective controlled trials.

BACKGROUND: This meta-analysis aimed to provide a pooled analysis of prospective controlled trials comparing the diagnostic accuracy of 22-G and 25-G needles on endoscopic ultrasonography (EUS-FNA) of the solid pancreatic mass. METHODS: We established a rigorous study protocol according to Cochrane Collaboration recommendations. We systematically searched the PubMed and Embase databases to identify articles to include in the meta-analysis. Sensitivity, specificity, and corresponding 95% confidence intervals were calculated for 22-G and 25-G needles of individual studies from the contingency tables. RESULTS: Eleven prospective controlled trials included a total of 837 patients (412 with 22-G vs 425 with 25-G). Our outcomes revealed that 25-G needles (92% [95% CI, 89%-95%]) have higher sensitivity than 22-G needles (88% [95% CI, 84%-91%]) on solid pancreatic mass EUS-FNA (P = 0.046). However, there were no significant differences between the 2 groups in overall diagnostic specificity (P = 0.842). The pooled positive and negative likelihood ratio of the 22-G needle were 12.61 (95% CI, 5.65-28.14) and 0.16 (95% CI, 0.12-0.21), respectively. The pooled positive likelihood ratio was 12.61 (95% CI, 5.65-28.14), and the negative likelihood ratio was 0.16 (95% CI, 0.12-0.21) for the 22-G needle. The pooled positive likelihood ratio was 8.44 (95% CI, 3.87-18.42), and the negative likelihood ratio was 0.13 (95% CI, 0.09-0.18) for the 25-G needle. The area under the summary receiver operating characteristic curve was 0.97 for the 22-G needle and 0.96 for the 25-G needle. CONCLUSION: Compared to the study of 22-G EUS-FNA needles, our study showed that 25-G needles have superior sensitivity in the evaluation of solid pancreatic lesions by EUS-FNA.

Role of neovibsanin scaffold in preservation of spatial cognitive functions of rats with chronic epilepsy.

The effect of neovibsanin scaffold (NS) on the spatial cognitive functions of rats with lobal cerebrovascular hypoperfusion was investigated. Rats were divided into long-term memory (LTM) and short-term memory (STM) groups with 15 rats in each group. The groups were subdivided into 3 groups: control group comprised of 5 rats without surgery, untreated group of 5 rats left without treatment after 2OV, and NS treatment group with 5 rats receiving 5 mg/kg daily for 12 weeks of 2VO operation. NS-treatment caused a marked decrease in the escape latency time and total distance travelled in the treatment group compared to untreated group which was evident from the working memory test. The animals of treatment group also showed significant improvement over that of untreated group in maze test performance. Furthermore, NS treatment also resulted in significant improvement in the probe memory test performance in treatment group compared to untreated group. These findings suggest that NS exhibits therapeutic effect on the spatial cognitive preservation in rats with chronic epilepsy.

The lower peripheral blood lymphocyte/monocyte ratio assessed during routine follow-up after standard first-line chemotherapy is a risk factor for predicting relapse in patients with diffuse large B-cell lymphoma.

A specific predictor during routine follow-up to ascertain risk for relapse after standard first-line chemotherapy in non-Hodgkin's lymphoma (NHL) has not been identified, although blood counts, lactate dehydrogenase (LDH) and imaging studies, such as computed tomography (CT) scans or positron emission tomography, have been recommended. Therefore, we studied the absolute lymphocyte count/absolute monocyte count ratio (ALC/AMC ratio) as a marker of poststandard first-line chemotherapy for predicting relapse in patients with diffuse large B-cell lymphoma (DLBCL). 220 consecutive DLBCL patients, originally diagnosed, treated with CHOP or R-CHOP and followed up at two institutions. ALC/AMC ratio was obtained at the time of confirmed relapse or last follow-up. Patients at the time of confirmed relapse (n = 163) had a lower ALC/AMC ratio compared with those at last follow-up (n = 57) (P < 0.001). ALC/AMC ratio at the time of confirmed relapse was a strong predictor for relapse with an area under the curve = 0.813 (P < 0.001). The sensitivity and specificity for ALC/AMC ratio at the time of confirmed relapse or at last follow-up were 68.1% and 87.7%, respectively, and the relative risk of relapse with an ALC/AMC ratio < 2.8 at the time of confirmed relapse or at last follow-up was 1.845 with an odds ratio of 15.247 (95% cumulative incidence: 6.473-35.916) after CHOP or R-CHOP in DLBCL. Patients with an ALC/AMC ratio (< 2.8) had a higher cumulative hazard rate of relapse compared with an ALC/AMC ratio (≥2.8) (P < 0.001). This study suggests that the lower ALC/AMC ratio can be used as a marker to assess risk of DLBCL relapse during routine follow-up after standard first-line chemotherapy.

[UPLC/Q-TOF-MS(E) based analysis of chemical composition of banxia xiexin decoction].

In order to clarify the chemical composition and source of Banxia Xiexin decoction quickly and comprehensively, whole and individual herbs of Banxia Xiexin decoction were analyzed by ultra-performance liquid chromatography with quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF-MS(E)). Under identical experiment conditions, chromatography results were compared between experiment groups. Based on the Q-TOF-MS(E) analysis, 74 peaks were identified on line. The herbal sources of these peaks were assigned. The results implied that flavonoids, triterpenoid saponins, alkaloids and glycosides were the main components in effective part of Banxia Xiexin decoction. The method established is simple and rapid for elucidation the constituents of Banxia Xiexin decoction and the results could be used for the quality control of Banxia Xiexin decoction.

Structure, stability, and electronic property of carbon-doped gold clusters Au(n)C- (n = 1-10): a density functional theory study.

The equilibrium geometric structures, relative stabilities, and electronic properties of Au(n)C(-) and Au(n+1)(-) (n = 1-10) clusters are systematically investigated using density functional theory with hyper-generalized gradient approximation. The optimized geometries show that one Au atom capped on Au(n-1)C(-) clusters is a dominant growth pattern for Au(n)C(-) clusters. In contrast to Au(n+1)(-) clusters, Au(n)C(-) clusters are most stable in a quasi-planar or three-dimensional structure because C doping induces the local non-planarity while the rest of the structure continues to grow in a planar mode, resulting in an overall non-2D configuration. The relative stability calculations show that the impurity C atom can significantly enhance the thermodynamic stability of pure gold clusters. Moreover, the effect of C atom on the Au(n)(-) host decreases with the increase of cluster size. The HOMO-LUMO gap curves show that the interaction of the C atom with Au(n)(-) clusters improves the chemical stability of pure gold clusters, except for Au3(-) and Au4(-) clusters. In addition, a natural population analysis shows that the charges in corresponding Au(n)C(-) clusters transfer from the Au(n)(-) host to the C atom. Meanwhile, a natural electronic configuration analysis also shows that the charges mainly transfer between the 2s and 2p orbitals within the C atom.

Structural characterization and identification of biflavones in Selaginella tamariscina by liquid chromatography-diode-array detection/electrospray ionization tandem mass spectrometry.

Biflavonoids, a special class of flavonoids, are widely distributed in gymnosperm plants and have various biological activities. They are also major bioactive ingredients in Selaginella tamariscina. In this work, we report the use of high-performance liquid chromatography with a diode-array detector (HPLC-DAD) and electrospray ionization multi-stage tandem mass spectrometry (ESI-MS(n)) to study the fragmentation behavior of three main types of biflavonoids using seven biflavonoid reference compounds and analyze the biflavonoids in Selaginella tamariscina. The most useful fragmentations in terms of structural identification are those involving the C-ring cleavage of biflavonoids. For amentoflavone-type biflavonoids (containing flavonoid parts I and II), fragmentation on the flavonoid part II at positions 1/3 and 0/4 are the primary pathways, whereas the chances are greater for C-ring cleavage fragmentation occurring on flavonoid part I at positions 1/3 and 1/4 for robustaflavone-type biflavonoids. However, the predominant diagnostic ions of the specific C-O-C-connected hinokiflavone-type biflavonoids are a series of ions resulting from the rupture of the connective C-O bond. Based on the fragmentation patterns of these reference compounds, 17 biflavonoids were identified in an extract of Selaginella tamariscina, three of which have not been previously reported as constituents of this plant. This study provides a powerful approach for the online structural elucidation and identification of different types of biflavonoids and positional isomers from Selaginella tamariscina and other biflavonoids distributed in related plants and prescriptions.

[The expression and significance of osteopontin in the development of nonalcoholic fatty liver fibrosis in rats].

OBJECTIVE: To investigate the changes of osteopontin (OPN) in the liver tissues during nonalcoholic fatty liver fibrosis in rats and to explore the effect of OPN in the development of nonalcoholic fatty liver fibrosis. METHODS: Fifty-six male Wistar rats were randomly divided into a control group (8 rats) and a high-fat diet group. The high-fat diet group was divided into 6 subgroups (8 rats in each subgroup) with high-fat feedings for 4, 8, 12, 16, 20 or 24 weeks. Conventional histochemical, HE, Masson-trichrome and immunohistochemical staining for alpha-smooth muscle actin (a-SMA) were performed with the liver histological preparations. The expression of OPN was detected with reverse transcription and polymerase chain reactions and Western blot. RESULTS: Levels of OPN in liver tissues in rat nonalcoholic fatty liver fibrosis induced by high-fat diet were significantly increased over those in the control group (F=7.15, P less than 0.01). OPN expressions were closely correlated with a-SMA and nonalcoholic fatty liver fibrosis, and correlation coefficients of the two groups were 0.94 and 0.82, and both P values were less than 0.01. CONCLUSION: Expression of OPN increases dramatically in the livers during the development of nonalcoholic fatty liver fibrosis, and OPN may play an important role in this event.