Identification of a signature of histone modifiers in kidney renal clear cell carcinoma.

Kidney renal clear cell carcinoma (KIRC) is a cancer that is closely associated with epigenetic alterations, and histone modifiers (HMs) are closely related to epigenetic regulation. Therefore, this study aimed to comprehensively explore the function and prognostic value of HMs-based signature in KIRC. HMs were first obtained from top journal. Then, the mRNA expression profiles and clinical information in KIRC samples were downloaded from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) datasets. Cox regression analysis and least absolute shrinkage and selection operator (Lasso) analysis were implemented to find prognosis-related HMs and construct a risk model related to the prognosis in KIRC. Kaplan-Meier analysis was used to determine prognostic differences between high- and low-risk groups. Immune infiltration and drug sensitivity analysis were also performed between high- and low-risk groups. Eventually, 8 HMs were successfully identified for the construction of a risk model in KIRC. The results of the correlation analysis between risk signature and the prognosis showed HMs-based signature has good prognostic value in KIRC. Results of immune analysis of risk models showed there were significant differences in the level of immune cell infiltration and expression of immune checkpoints between high- and low-risk groups. The results of the drug sensitivity analysis showed that the high-risk group was more sensitive to several chemotherapeutic agents such as Sunitinib, Tipifarnib, Nilotinib and Bosutinib than the low-risk group. In conclusion, we successfully constructed HMs-based prognostic signature that can predict the prognosis of KIRC.

Retrograde intrarenal surgery with intelligent control of renal pelvic pressure for staghorn calculi: a case report.

Percutaneous nephrolithotomy is the gold standard treatment for staghorn calculi. However, this study reviews a case of an almost complete removal of staghorn calculi following one session of retrograde intrarenal surgery with intelligent control of renal pelvic pressure (RIRS-ICP). A 45 years-old female patient with an 8.3 × 4.5 cm complete staghorn stone was infected with Proteus mirabilis. Two sensitive antibiotics, piperacillin tazobactam and etimicin, were administered for 3 days. Semirigid 7/8.4 Fr ureteroscope was used to treat the renal pelvis and upper calyceal calculi for 57 min. A 550 µm holmium laser fiber with 2.0 J × 30 Hz was set. Next, a disposable flexible ureteroscope of 8.4 Fr was used to address residual middle and lower calyx stones for 94 min. A 200 µm holmium laser fiber with 1.0 J × 30 Hz was set. The renal pelvis pressure was controlled within 15 mmHg. A 2 mm CT scan on the first postoperative day showed inferior caliceal residue of approximately 1.0 × 0.6 cm. No complications occurred. This suggests that RIRS-ICP is a safe and effective treatment for staghorn calculi.

Ureteroscopic lithotripsy with pressure-measuring ureteral access sheath for large ureteral stones.

INTRODUCTION: To evaluate the safety and efficacy of ureteroscopic lithotripsy with pressure-measuring ureteral access sheath (PM-UAS) for large ureteral stones. MATERIAL AND METHODS: A total of 258 consecutive patients with large ureteral stones ≥15 mm was enrolled. They were treated by ureteroscopic lithotripsy with PM-UAS in the oblique supine lithotomy position. The technology can precisely monitor and automatically control cavity pressure. The cavity pressure control value was set at -15 mmHg∼-5 mmHg. The cavity pressure limit value was set at 30 mmHg. Infusion flow rate was set at 100-200 ml/min. Postoperative data such as stone-free rate and complications were analyzed. RESULTS: PM-UAS was successfully implanted in 225 patients at one stage. Eighteen cases of patients who had failed the first surgery were successfully treated with a second operation. Fifty-one cases with stones migrating up to the kidney were converted to flexible lithotripsy. The other 15 cases were converted to percutaneous nephrolithotomy due to significant ureteral stenosis. The operative time was 49.5 ± 11.2 min. The stone-free rates after one month and three months were 87.2% (212/243) and 94.2% (229/243), respectively. Complications from grade I to II were observed in 25(10.3%) patients. No other complications from grade III to V were noted. CONCLUSION: The ureteroscopic lithotripsy with PM-UAS is safe and efficacious for large ureteral stones.

Xanthomonas chitinilytica sp. nov., a novel chitinolytic bacterium isolated from a microbial fermentation bed material.

A Gram-stain-negative bacterium, H13-6T, was isolated from a microbial fermentation bed material collected from a pig farm located in Yan'an, Shaanxi, China. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain H13-6T was affiliated with the genus Xanthomonas and showed highest similarity to strain Xanthomonas maliensis M97T (98.38%), Xanthomonas prunicola CFBP 8353T (98.26%) and Xanthomonas oryzae ATCC 35933T (98.11%). The pairwise ortho Average Nucleotide Identity values and the digital DNA-DNA hybridization values between strain H13-6T and the other Xanthomonas species were all below their respective cut-offs. Two genes encoding for chitinase were found and the strain showed a strong chitin-degrading activity. The major fatty acids were Iso-C15:0 (55.9%), Antesio-C15:0 (7.4%) and Iso-C11:0 (5.5%) and the major polar lipids were diphosphatidylglycerol, phosphatidyglycerol and phosphatidylethanolamine. Based on the phenotypic properties and phylogenetic distinctiveness, Xanthomonas chitinilytica was proposed as a novel species of the genus Xanthomonas, with strain H13-6T (= CGMCC 1.61317T = NBRC 115641T) as type strain.

Application of three-dimensional printing in cardiovascular diseases: a bibliometric analysis.

AIM: This paper aimed to explore the application of three-dimensional (3D) printing in cardiovascular diseases, to reach an insight in this field and prospect the future trend. METHODS: The articles were selected from the Web of Science Core Collection database. Excel 2019, VOSviewer 1.6.16, and CiteSpace 6.1.R6 were used to analyze the information. RESULTS: A total of 467 papers of 3D printing in cardiovascular diseases were identified, and the first included literature appeared in 2000. A total of 692 institutions from 52 countries participated in the relevant research, while the United States of America contributed to 160 articles and were in a leading position. The most productive institution was Curtin University , and Zhonghua Sun who has posted the most articles ( n =8) was also from there. The Frontiers in Cardiovascular Medicine published most papers ( n =25). The Journal of Thoracic and Cardiovascular Surgery coveted the most citations ( n =520). Related topics of frontiers will still focus on congenital heart disease, valvular heart disease, and left atrial appendage closure. CONCLUSIONS: The authors summarized the publication information of the application of 3D printing in cardiovascular diseases related literature from 2000 to 2023, including country and institution of origin, authors, and publication journal. This study can reflect the current hotspots and novel directions for the application of 3D printing in cardiovascular diseases.

Association Analyses between Single Nucleotide Polymorphisms in ZFAT, FBN1, FAM184B Genes and Litter Size of Xinggao Mutton Sheep.

Previous studies have screened key candidate genes for litter size in sheep, including fibrillin-1 (FBN1), family with sequence similarity 184 member B (FAM184B) and zinc finger and AT-hook domain containing (ZFAT). Therefore, it is necessary to verify these genes in the Xinggao mutton sheep population and determine the associated loci for litter size. In this study, three loci (FBN1 g.160338382 T > C, FAM184B g.398531673 C > T and ZFAT g.20150315 C > T) were firstly screened based on the population differentiation coefficient between the polytocous and monotocous sheep groups. Then, population genetic analysis and association analysis were performed on these loci. The results revealed that the g.160338382 T > C in FBN1 was significantly associated with the litter size of sheep. Moreover, there was no significant interaction effect between the g.160338382 T > C locus and FecB on litter size. Notably, g.160338382 T > C is adjacent to the anterior border of exon 58 and belongs to a splice polypyrimidine tract variant, which may lead to alternative splicing and ultimately cause changes in the structure and function of the protein. In summary, our results provided a potentially effective genetic marker for improving the litter size of sheep.

Dynamic Crushing Behavior of Ethylene Vinyl Acetate Copolymer Foam Based on Energy Method.

This paper aimed to experimentally clarify the dynamic crushing mechanism and performance of ethylene vinyl acetate copolymer (EVA) and analyze the influence of density and thickness on its mechanical behavior and energy absorption properties under dynamic impact loadings. Hence, a series of dynamic compression tests were carried out on EVA foams with different densities and thicknesses. When the impact energy is 66.64 J, for foam with a density of 150 kg/m3, the maximum contact force, maximum displacement, maximum strain, absorbed energy, and specific energy absorption (SEA) increased by 20 ± 2%, -38.5 ± 2%, -38.5 ± 2%, 4 ± 2%, and 105 ± 2%, respectively, compared to foam with a density of 70 kg/m3. The ratios of absorbed energy to impact energy for different thickness specimens are almost equal. The specimen density has no effect on the efficiency of energy absorption and has a greater effect on the SEA. Meanwhile, when the impact energy-to-thickness ratio is 1680 J/m, compared to foam with a thickness of 30 mm, the maximum contact force, maximum displacement, maximum strain, absorbed energy, and SEA for foam with a thickness of 60 mm increased by 28.5 ± 2%, 211.3 ± 2%, 56.6 ± 2%, 100.8 ± 2%, and 0.4 ± 0.5%, respectively. When the impact energy is 66.64 J, compared to foam with a thickness of 30 mm, the maximum contact force, maximum displacement, maximum stain, absorbed energy, and SEA for foam with a thickness of 60 mm increased by -42.5 ± 2%, 163.5 ± 2%, 31.7 ± 2%, 4.1 ± 2%, and 4.1 ± 2%, respectively. The SEA of two different-thickness EVA specimens is almost equal, about 2.8 J/g. The ratios of absorbed energy to impact energy for different thickness specimens are almost equal, both at 72%. The specimen thickness has no effect on the efficiency of energy absorption and has a greater effect on the maximum contact force. In the range of impact energy, thickness, and density studied, the absorbed energy and SEA are not affected by the thickness of EVA specimens and are determined by the impact energy. The density has no significant effect on the absorbed energy but has a greater effect on the SEA. However, for EVA foams, the greater the density, the greater the mass, and the higher the cost. Taking into account lightweight and cost factors, when optimizing cushioning design within a safe range, we can choose EVA foams with a smaller density and thickness.

A probiotic bi-functional peptidoglycan hydrolase sheds NOD2 ligands to regulate gut homeostasis in female mice.

Secreted proteins are one of the direct molecular mechanisms by which microbiota influence the host, thus constituting a promising field for drug discovery. Here, through bioinformatics-guided screening of the secretome of clinically established probiotics from Lactobacillus, we identify an uncharacterized secreted protein (named LPH here) that is shared by most of these probiotic strains (8/10) and demonstrate that it protects female mice from colitis in multiple models. Functional studies show that LPH is a bi-functional peptidoglycan hydrolase with both N-Acetyl-ß-D-muramidase and DL-endopeptidase activities that can generate muramyl dipeptide (MDP), a NOD2 ligand. Different active site mutants of LPH in combination with Nod2 knockout female mice confirm that LPH exerts anti-colitis effects through MDP-NOD2 signaling. Furthermore, we validate that LPH can also exert protective effects on inflammation-associated colorectal cancer in female mice. Our study reports a probiotic enzyme that enhances NOD2 signaling in vivo in female mice and describes a molecular mechanism that may contribute to the effects of traditional Lactobacillus probiotics.

Application value of CT-guided localization using a coil in combination with medical adhesive in sublobar resection.

PURPOSE: To explore the application value of CT-guided localization using a coil in combination with medical adhesive in sublobar resection. METHODS: The clinical data of 90 patients who had small pulmonary nodules and received thoracoscopic sublobar resection during the period from September 2021 to October 2022 in the Department of Thoracic Surgery, Juxian People's Hospital, Shandong Province, were retrospectively analyzed. RESULTS: The diameters of 95 pulmonary nodules in the 90 patients in the whole group ranged from 0.40 to 1.24 cm, and their distances from the visceral pleura ranged from 0.51 to 2.15 cm. In these patients, percutaneous lung puncture was successfully performed under local anesthesia, through which coils were implanted in the nodules and medical adhesive was injected around the nodules, with a success rate of localization of 100%. Localization complications included 10 cases of asymptomatic pneumothorax, 9 cases of intrapulmonary hemorrhage, 5 cases of severe pain, and 1 case of pleural reaction, all of which required no special treatment. After preoperative localization, the success rate of resection of pulmonary nodules was 100%, and sufficient surgical margins were obtained. CONCLUSION: CT-guided localization using a coil in combination with medical adhesive is a safe, effective, and simple localization method that can meet the requirements of thoracic surgeons for intraoperative localization; for small pulmonary nodules, especially those small-sized and deep-located ground-glass nodules containing few solid mass, this method has important clinical application value, which is a preoperative localization technique worthy of wide application in clinical practice.

Innovative integration of augmented reality and optical surface imaging: A coarse-to-precise system for radiotherapy positioning.

BACKGROUND: Traditional methods of radiotherapy positioning have shortcomings such as fragile skin-markers, additional doses, and lack of information integration. Emerging technologies may provide alternatives for the relevant clinical practice. PURPOSE: To propose a noninvasive radiotherapy positioning system integrating augmented reality (AR) and optical surface, and to evaluate its feasibility in clinical workflow. METHODS: AR and structured light-based surface were integrated to implement the coarse-to-precise positioning through two coherent steps, the AR-based coarse guidance and the optical surface-based precise verification. To implement quality assurance, recognition of face and pattern was used for patient authentication, case association, and accessory validation in AR scenes. The holographic images reconstructed from simulation computed tomography (CT) images, guided the initial posture correction by virtual-real alignment. The point clouds of body surface were fused, with the calibration and pose estimation of structured light cameras, and segmented according to the preset regions of interest (ROIs). The global-to-local registration for cross-source point clouds was achieved to calculate couch shifts in six degrees-of-freedom (DoF), which were ultimately transmitted to AR scenes. The evaluation based on phantom and human-body (4 volunteers) included, (i) quality assurance workflow, (ii) errors of both steps and correlation analysis, (iii) receiver operating characteristic (ROC), (iv) distance characteristics of accuracy, and (v) clinical positioning efficiency. RESULTS: The maximum errors in phantom evaluation were 3.4 ± 2.5 mm in Vrt and 1.4 ± 1.0° in Pitch for the coarse guidance step, while 1.6 ± 0.9 mm in Vrt and 0.6 ± 0.4° in Pitch for the precise verification step. The Pearson correlation coefficients between precise verification and cone beam CT (CBCT) results were distributed in the interval [0.81, 0.85]. In ROC analysis, the areas under the curve (AUC) were 0.87 and 0.89 for translation and rotation, respectively. In human body-based evaluation, the errors of thorax and abdomen (T&A) were significantly greater than those of head and neck (H&N) in Vrt (2.6 ± 1.1 vs. 1.7 ± 0.8, p < 0.01), Lng (2.3 ± 1.1 vs. 1.4 ± 0.9, p < 0.01), and Rtn (0.8 ± 0.4 vs. 0.6 ± 0.3, p = 0.01) while relatively similar in Lat (1.8 ± 0.9 vs. 1.7 ± 0.8, p = 0.07). The translation displacement range, after coarse guidance step, required for high accuracy of the optical surface component of the integrated system was 0-42 mm, and the average positioning duration of the integrated system was significantly less than that of conventional workflow (355.7 ± 21.7 vs. 387.7 ± 26.6 s, p < 0.01). CONCLUSIONS: The combination of AR and optical surface has utility and feasibility for patient positioning, in terms of both safety and accuracy.

Clearance of bacteria from lymph nodes in sheep immunized with Brucella suis S2 vaccine is associated with M1 macrophage activation.

Ovine brucellosis is a global zoonotic disease of sheep caused by Brucella melitensis, which inflicts a significant burden on human and animal health. Brucella suis strain S2 (B. suis S2) is a smooth live attenuated vaccine for the prevention of ovine brucellosis in China. However, no previous studies have assessed the immunogenicity of B. suis S2 vaccine after oral immunization in sheep. Here, we attempted to evaluate the ovine immune response over the course of B. suis S2 immunization and to identify in vivo predictors for vaccine development. Body temperature, serum Brucella antibodies, serum cytokines (IL-12p70 and interferon [IFN]-γ), and bacterial load in the mandibular lymph nodes (LN), superficial cervical LN, superficial inguinal LN, and spleen were investigated to determine the safety and efficacy of the vaccine. The abnormal body temperature of sheep occurred within 8 days post-infection (dpi). Brucella suis S2 persisted for a short time (< 21 dpi) in the mandibular LN. The highest level of IL-12p70 was observed at 9 dpi, whereas serum IFN-γ levels peaked at 12 dpi. Transcriptome analysis and quantitative reverse transcription PCR were performed to determine gene expression profiles in the mandibular LN of sheep. Antigen processing and presentation pathway was the dominant pathway related to the dataset. Our studies suggest that the immune response in ovine LN resembled type 1 immunity with the secretion of IL-12p70 and IFN-γ after B.suis S2 immunization and the vaccine may eliminate Brucella via stimulation of M1 macrophages through the course of Th cells.

Microbial community succession during crude oil-degrading bacterial enrichment cultivation and construction of a degrading consortium.

Microbial community succession during the enrichment of crude-oil-degrading bacteria was analyzed using Illumina high-throughput sequencing to guide bacterial isolation and construction of a bacterial consortium. Community change occurred in 6 days; the most abundant phylum changed from Proteobacteria to Actinobacteria; the most abundant genera were Dietzia and unspecified_Idiomarinaceae. Two crude oil-degrading strains, Rhodococcus sp. OS62-1 and Dietzia sp. OS33, and one weak-crude-oil-degrading strain, Pseudomonas sp. P35, were isolated. A consortium comprising Rhodococcus sp. OS62-1 and Pseudomonas sp. P35 showed the highest crude-oil-degrading efficiency, reaching 85.72 ± 3.21% within 7 days, over a wide pH range (5-11) and salinity (0-80 g·L-1). Consumption of saturated hydrocarbons, aromatic hydrocarbons, and resins was greater by the consortium than by a single strain, as was degradation of short-chain-alkanes (C13-C17) according to gas-chromatography. The bacterial consortium provides technical support for bioremediation of crude oil pollution.

Gut microbial DL-endopeptidase alleviates Crohn's disease via the NOD2 pathway.

The pattern-recognition receptor NOD2 senses bacterial muropeptides to regulate host immunity and maintain homeostasis. Loss-of-function mutations in NOD2 are associated with Crohn's disease (CD), but how the variations in microbial factors influence NOD2 signaling and host pathology is elusive. We demonstrate that the Firmicutes peptidoglycan remodeling enzyme, DL-endopeptidase, increased the NOD2 ligand level in the gut and impacted colitis outcomes. Metagenomic analyses of global cohorts (n = 857) revealed that DL-endopeptidase gene abundance decreased globally in CD patients and negatively correlated with colitis. Fecal microbiota from CD patients with low DL-endopeptidase activity predisposed mice to colitis. Administering DL-endopeptidase, but not an active site mutant, alleviated colitis via the NOD2 pathway. Therapeutically restoring NOD2 ligands with a DL-endopeptidase-producing Lactobacillus salivarius strain or mifamurtide, a clinical analog of muramyl dipeptide, exerted potent anti-colitis effects. Our study suggests that the depletion of DL-endopeptidase contributes to CD pathogenesis through NOD2 signaling, providing a therapeutically modifiable target.

[Composition and histopathological features of prostatic calculi in patients with benign prostatic hyperplasia].

OBJECTIVE: To analyze the composition of prostatic calculus in patients with BPH and explore its pathogenic factors and histopathological characteristics. METHODS: Strictly following the inclusion and exclusion criteria, we included in this retrospective study 580 cases of bipolar transurethral plasma kinetic prostatectomy (TUPKP) performed in our hospital from May 2015 to May 2019, analyzed the histopathological and calculus-composition features of the patients with BPH complicated by prostatic calculi (the BPH+PC group) and the histopathological data of those with BPH only (the BPH group). We compared the related factors between the two groups of patients and performed uni- and multivariate logistic regression analyses of the data on those in the BPH+PC group. RESULTS: The incidence rate of chronic inflammation was significantly higher in the BPH+PC than in the BPH group (83.1% vs 61.1%, P < 0.05), 90% of the cases moderate to severe and 81% with inflammatory cells mainly distributed in the prostate gland in the BPH+PC group, and 74% with inflammatory cells chiefly distributed in the prostate gland and stroma in the BPH group, with statistically significant difference between the two groups (P < 0.05). Prostatic calculi were found in 302 (52.1%) of the patients, including 71 cases of simple calculi (23.5%) and 231 cases of mixed calculi (76.5%). As for the chemical composition, calcium oxalate was detected in 212 cases (70.2%), carbonate apatite in 206 (68.2%), magnesium ammonium phosphate in 158 (52.3%), and uric acid calculi in 19 (6.3%). The calculus composition was not correlated with the age of the patients. There were statistically significant differences between the two groups of patients in age, prostate volume and IPSS (P < 0.05), but not in the PSA level, postvoid residual urine volume (PRV) or maximum urinary flow rate (Qmax) (P > 0.05). Logistic regression analyses showed that prostatic calculus was significantly correlated with chronic inflammation of the prostate, the patient's age and IPSS (P < 0.05) but not with the PSA level, PRV or Qmax (P > 0.05). CONCLUSIONS: Prostatic calculus has a high incidence in BPH patients and varies widely in composition, chiefly consisting of calcium oxalate and carbonate apatite. The major factors contributing to prostatic calculi include chronic inflammation of the prostate (primarily the severe type), age and BPH. Prostate calculi may aggravate lower urinary tract symptoms, especially urinary storage symptoms, in patients with BPH, but not significantly affect the PSA level.？.

Oncogenic gene TRIM10 confers resistance to cisplatin in osteosarcoma cells and activates the NF-κB signaling pathway.

Deregulation of tripartite motif (TRIM) family proteins contribute to multiple biological processes such as neurodegeneration, development, inflammation, cell survival, apoptosis, and carcinogenesis. However, the biological function and molecular mechanism of TRIM family proteins in osteosarcoma chemoresistance remain unclear. In the current study, we found the protein expression of TRIM10 was markedly overexpressed in cisplatin resistance's osteosarcoma tissues and TRIM10 overexpression was inversely correlated with osteosarcoma patient survival. Furthermore, overexpression of TRIM10 confers cisplatin resistance on osteosarcoma cells; however, repressing TRIM10 sensitized osteosarcoma cell lines to cisplatin cytotoxicity in vitro. Mechanically, TRIM10 upregulated the nuclear levels of p65, thereby activating canonical NF-κB signaling. Taken together, our results suggest that TRIM10 contributed to cisplatin resistance in osteosarcoma cells, and targeting the TRIM10/p65 axis may represent a promising strategy to enhance cisplatin response in osteosarcoma patients with chemoresistance.

LncR2metasta: a manually curated database for experimentally supported lncRNAs during various cancer metastatic events.

Mounting evidence has shown the involvement of long non-coding RNAs (lncRNAs) during various cancer metastatic events (abbreviated as CMEs, e.g. cancer cell invasion, intravasation, extravasation, proliferation, etc.) that may cooperatively facilitate malignant tumor spread and cause massive patient deaths. The study of lncRNA-CME associations might help understand lncRNA functions in metastasis and present reliable biomarkers for early dissemination detection and optimized treatment. Therefore, we developed a database named 'lncR2metasta' by manually compiling experimentally supported lncRNAs during various CMEs from existing studies. LncR2metasta documents 1238 associations between 304 lncRNAs and 39 CMEs across 54 human cancer subtypes. Each entry of lncR2metasta contains detailed information on a lncRNA-CME association, including lncRNA symbol, a specific CME, brief description of the association, lncRNA category, lncRNA Entrez or Ensembl ID, lncRNA genomic location and strand, lncRNA experiment, lncRNA expression pattern, detection method, target gene (or pathway) of lncRNA, lncRNA regulatory role on a CME, cancer name and the literature reference. An easy-to-use web interface was deployed in lncR2metasta for its users to easily browse, search and download as well as to submit novel lncRNA-CME associations. LncR2metasta will be a useful resource in cancer research community. It is freely available at http://lncR2metasta.wchoda.com.

[SBi4211 alleviates gp120-induced central nervous system injury via inhibiting S100B/ RAGE].

OBJECTIVE: To explore the protective effect of SBi4211 (heptamidine), an inhibitor of S100B, against central nervous system injury induced by HIV-1 envelope protein gp120. METHODS: In an in vitro model, U251 glioma cells were co-cultured with SH-SY5Y cells to explore the protective effect of SBi4211 against gp120-induced central nervous system injury. In a gp120 transgenic (Tg) mouse model (8 months old) mimicking HIV-associated neurocognitive disorder (HAND), the effect of treatment with gp120 or both gp120 and SBi4211 on neuronal activity and apoptosis were assessed using Cell Counting kit-8 (CCK-8) and flow cytometry. ELISA, Western blotting and immunohistochemistry were used to determine the expression levels of S100B, RAGE, GFAP, NeuN, Syn, MAP-2 and the inflammatory factors IL-6 and TNF-α. RESULTS: In the cell co-culture system, SBi4211 treatment significantly inhibited gp120-induced expression of S100B, RAGE and GFAP in U251 cells (P < 0.001), reduced the levels of inflammatory factors iNOS, IL-6 and TNF-α (P < 0.001) and enhanced the expressions of neuron-related proteins NeuN, Syn and MAP-2 (P < 0.001). In the transgenic mouse model, SBi4211 treatment significantly reduced the expressions of S100B, RAGE and inflammation levels (P < 0.05), inhibited the activation of astrocytes in the brain, and maintained the integrity of the neurons (P < 0.05). CONCLUSIONS: SBi4211 can protect neurons from gp120-induced neurotoxicity possibly by inhibiting the S100B/ RAGE-mediated signaling pathway.

A predicted protein functional network aids in novel gene mining for characteristic secondary metabolites in tea plant (Camellia sinensis).

Modeling a protein functional network in concerned species is an efficient approach for identifying novel genes in certain biological pathways. Tea plant (Camellia sinensis) is an important commercial crop abundant in numerous characteristic secondary metabolites (e.g., polyphenols, alkaloids, alkaloids) that confer tea quality and health benefits. Decoding novel genes responsible for tea characteristic components is an important basis for applied genetic improvement and metabolic engineering. Herein, a high-quality protein functional network for tea plant (TeaPoN) was predicted using cross-species protein functional associations transferring and integration combined with a stringent biological network criterion control. TeaPoN contained 31,273 nonredundant functional interactions among 6,634 tea proteins (or genes), with general network topological properties such as scale-free and small-world. We revealed the modular organization of genes related to the major three tea characteristic components (theanine, caffeine, catechin) in TeaPoN, which served as strong evidence for the utility of TeaPoN in novel gene mining. Importantly, several case studies regarding gene identification for tea characteristic components were presented. To aid in the use of TeaPoN, a concise web interface for data deposit and novel gene screening was developed (http://teapon.wchoda.com). We believe that TeaPoN will serve as a useful platform for functional genomics studies associated with characteristic secondary metabolites in tea plant.

Quercetin inhibits TNF-α induced HUVECs apoptosis and inflammation via downregulating NF-kB and AP-1 signaling pathway in vitro.

BACKGROUND: Quercetin, a major flavonol, wildly exists in plantage, which has been reported to have an anti-apoptosis and anti-inflammation effects on vascular endothelial cells, but its underlying molecular mechanisms remain unclear. OBJECTIVE: The aim of this study was to investigate the mechanisms of how quercetin inhibits tumor necrosis factor alpha (TNF-α) induced human umbilical vein endothelial cells (HUVECs) apoptosis and inflammation. METHODS AND RESULTS: HUVECs were preconditioned with quercetin for 18 hours, and subsequently treated with TNF-α for 6 hours to induce apoptosis. The expression of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, ß-actin mRNA was then detected by RT-PCR. Flow cytometry was used to estimate the apoptosis rates, and the expression of activator protein 1 (AP-1) and nuclear factor kappa B (NF-κB) was measured by Western blot. TNF-α induced elevated apoptosis rates and upregulation of VCAM-1, ICAM-1, and E-selectin were meaningfully reduced in HUVECs by pretreatment with quercetin. In addition, quercetin also inhibited the activation of AP-1and NF-κB. CONCLUSION: Results indicate that quercetin could suppress TNF-α induced apoptosis and inflammation by blocking NF-κB and AP-1 signaling pathway in HUVECs, which might be one of the underlying mechanisms in treatment of coronary heart disease.

Size-Specific Dose Estimates of Radiation Based on Body Weight and Body Mass Index for Chest and Abdomen-Pelvic CTs.

BACKGROUND: To correlate body weight, body mass index (BMI), and water-equivalent diameter (d w) and to assess size-specific dose estimates (SSDEs) based on body weight and BMI for chest and abdomen-pelvic CT examinations. METHODS: An in-house program was used to calculate d w, size-dependent conversion factor (f), and SSDE for 1178 consecutive patients undergoing chest and abdomen-pelvic CT examinations. Associations among body weight, BMI, and d w were determined, and linear equations were generated using linear regression analysis of the first 50% of the patient population. SSDEs (SSDEweight and SSDEBMI) were calculated based on body weight and BMI as d w surrogates on the second 50% of the patient population. Mean root-mean-square errors of SSDEweight and SSDEBMI were computed with SSDE from the axial images as reference values. RESULTS: Both body weight and BMI correlated strongly with d w for the chest (r = 0.85, 0.87, all p < 0.001) and abdomen-pelvis (r = 0.85, 0.86, all p < 0.001). Mean values of SSDEweight and SSDEBMI based on the linear equations for body weight, BMI, and d w were in close agreement with SSDE from the axial images, with overall mean root-mean-square errors of 0.62 mGy (6.10%) and 0.57 mGy (5.65%), for chest, and 0.76 mGy (5.61%) and 0.71 mGy (5.22%), for abdomen-pelvis, respectively. CONCLUSIONS: Both body weight and BMI, serving as d w surrogates, can be used to calculate SSDEs in the chest and abdomen-pelvis CT examinations, providing values comparable to SSDEs from the axial images, with an overall mean root-mean-square error of less than 0.76 mGy or 6.10%.