The truncated AXIN1 isoform promotes hepatocellular carcinoma metastasis through SRSF9-mediated exon 9 skipping.

Axis inhibitor protein 1 (AXIN1) is a protein recognized for inhibiting tumor growth and is commonly involved in cancer development. In this study, we explored the potential molecular mechanisms that connect alternative splicing of AXIN1 to the metastasis of hepatocellular carcinoma (HCC). Transcriptome sequencing, RT‒PCR, qPCR and Western blotting were utilized to determine the expression levels of AXIN1 in human HCC tissues and HCC cells. The effects of the AXIN1 exon 9 alternative splice isoform and SRSF9 on the migration and invasion of HCC cells were assessed through wound healing and Transwell assays, respectively. The interaction between SRSF9 and AXIN1 was investigated using UV crosslink RNA immunoprecipitation, RNA pulldown, and RNA immunoprecipitation assays. Furthermore, the involvement of the AXIN1 isoform and SRSF9 in HCC metastasis was validated in a nude mouse model. AXIN1-L (exon 9 including) expression was downregulated, while AXIN1-S (exon 9 skipping) was upregulated in HCC. SRSF9 promotes the production of AXIN1-S by interacting with the sequence of exons 8 and 10 of AXIN1. AXIN1-S significantly promoted HCC cells migration and invasion by activating the Wnt pathway, while the opposite effects were observed for AXIN1-L. In vivo experiments demonstrated that AXIN1-L inhibited HCC metastasis, whereas SRSF9 promoted HCC metastasis in part by regulating the level of AXIN1-S. AXIN1, a tumor suppressor protein that targets the AXIN1/Wnt/ß-catenin signaling axis, may be a promising prognostic factor and a valuable therapeutic target for HCC.

Reason and control strategy for denitrification and anammox sludge flotation in nitrogen removal process: Mechanisms, strategies and perspectives.

Anaerobic biological treatment technology, especially denitrification and anaerobic ammonia oxidation (anammox) technology as mainstream process, played dominant role in the field of biological wastewater treatment. However, the above process was prone to sludge floating during high load operation and thereby affecting the efficient and stable operation of the system. Excessive production of extracellular polymeric substance (EPS) was considered to be the main reason for anaerobic granular sludge flotation, but the summaries in this area were not comprehensive enough. In this review, the potential mechanisms of denitrification and anammox sludge floatation were discussed from the perspective of granular sludge structural characteristics, nutrient transfer, and microbial flora change respectively, and the corresponding control strategies were also summarized. Finally, this paper indicated that future research on sludge flotation should focus on reducing the negative effects of EPS in sludge particles.

Cathepsin K inhibition alleviates periodontal bone resorption by promoting type H vessel formation through PDGF-BB/PDGFR-ß axis.

OBJECTIVES: To explore the effects of cathepsin K (CTSK) inhibition on type H vessel formation and alveolar bone resorption within periodontitis. METHODS: Conditioned media derived from preosteoclasts pretreated with the CTSK inhibitor odanacatib (ODN), ODN supplemented small interfering RNA targeting PDGF-BB (si-PDGF-BB), or PBS were prepared, to assess their proangiogenic effects on endothelial cells (HUVECs). A series of angiogenic-related assays were conducted to evaluate HUVEC proliferation, migration, and tube formation abilities in vitro. In addition, qRT-PCR and Western blot assays were employed to examine the expression levels of genes/proteins related to PDGF-BB/PDGFR-ß axis components. A mouse periodontitis model was established to evaluate the effects of CTSK inhibition on type H vessel formation. RESULTS: CTSK inhibition promoted PDGF-BB secretion from preosteoclasts and proliferation, migration, and tube formation activities of HUVECs in vitro. However, the conditioned medium from preosteoclasts pretreated by si-PDGF-BB impaired the angiogenic activities of HUVECs. This promoted angiogenesis function by CTSK inhibition may be mediated by the PDGF-BB/PDGFR-ß axis. Functionally, in vivo studies demonstrated that CTSK inhibition significantly accelerated type H vessel formation and alleviated bone loss within periodontitis. CONCLUSION: CTSK inhibition promotes type H vessel formation and attenuates alveolar bone resorption within periodontitis via PDGF-BB/PDGFR-ß axis.

CYD0281, a Bcl-2 BH4 domain antagonist, inhibits tumor angiogenesis and breast cancer tumor growth.

BACKGROUND: B-cell lymphoma 2 (Bcl-2) family proteins are key regulators of apoptosis, which possess four conserved Bcl-2 homologies (BH) domains. Among the BH domains, the BH3 domain is considered as a potent 'death domain' while the BH4 domain is required for anti-apoptotic activity. Bcl-2 can be converted to a pro-apoptotic molecule through the removal or mutation of the BH4 domain. Bcl-2 is considered as an inducer of angiogenesis, which can promote tumor vascular network formation and further afford nutrients and oxygen to promote tumor progression. However, whether disrupting the function of the BH4 domain to convert Bcl-2 into a pro-apoptotic molecule could make Bcl-2 possess the potential for anti-angiogenic therapy remains to be defined. METHODS: CYD0281 was designed and synthesized according to the lead structure of BDA-366, and its function on inducing a conformational change of Bcl-2 was further evaluated via immunoprecipitation (IP) and immunofluorescence (IF) assays. Moreover, the function of CYD0281 on apoptosis of endothelial cells was analyzed via cell viability, flow cytometry, and western blotting assays. Additionally, the role of CYD0281 on angiogenesis in vitro was determined via endothelial cell migration and tube formation assays and rat aortic ring assay. Chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) models, breast cancer cell xenograft tumor on CAM and in mouse models as well as the Matrigel plug angiogenesis assay were used to explore the effects of CYD0281 on angiogenesis in vivo. RESULTS: We identified a novel potent small-molecule Bcl-2-BH4 domain antagonist, CYD0281, which exhibited significant anti-angiogenic effects both in vitro and in vivo, and further inhibited breast cancer tumor growth. CYD0281 was found to induce conformational changes in Bcl-2 through the exposure of the BH3 domain and convert Bcl-2 from an anti-apoptotic molecule into a cell death inducer, thereby resulting in the apoptosis of vascular endothelial cells. CONCLUSIONS: This study has revealed CYD0281 as a novel Bcl-2-BH4 antagonist that induces conformational changes of Bcl-2 to convert to a pro-apoptotic molecule. Our findings indicate that CYD0281 plays a crucial role in anti-angiogenesis and may be further developed as a potential anti-tumor drug candidate for breast cancer. This work also provides a potential anti-angiogenic strategy for breast cancer treatment.

Dietary metabolizable energy and crude protein levels affect the performance, egg quality and biochemical parameters of a dual-purpose chicken.

Effects of dietary metabolizable energy (ME) and crude protein (CP) level on performance, egg quality and biochemical parameters were studied in a dual-purpose chicken-Beijing You Chicken (BYC) at peak laying period. A 3 × 3 factorial experiment was arranged, including 3 levels of dietary ME (11.31, 11.51, 11.71 MJ/kg) and 3 levels of dietary CP (14%, 15%, 16%). The results showed that dietary CP level alone and the interaction of ME by CP affected the total feed intake (TFI) during 27-30 wks, dietary ME level affected the mortality rate of 27-34 wks of age (p = 0.018), with the highest mortality rate found in 11.31 MJ/kg group (3.10%). The albumen height (AH), Haugh unit (HU) and egg grade (EG) of 16% group was higher than those in 14% and 15% groups (p < 0.05). Serum immunoglobulin G content in 11.31 MJ/kg group was lower than in 11.51 MJ/kg and 11.71 MJ/kg groups (p = 0.037). The present study suggested that dietary levels of 11.51 MJ/kg ME and 16.0% CP are enough to maintain the performance and egg quality of BYC at peak laying period. 11.31 MJ/kg ME increased the mortality of the chicken, which may be related to the decrease of the humoral immune function and antioxidative capability.

Effect of low-level laser therapy on orthodontic dental alignment: a systematic review and meta-analysis.

The aim of this study is to systematically summarize the available evidence regarding low-level laser therapy (LLLT) speed-up effect on dental alignment in comprehensive orthodontic treatment. An extensive electronic search was conducted in PubMed, ScienceDirect, Cochrane, Web of Science, and Scopus up to February 20, 2023. The Cochrane risk of bias tool and the Newcastle-Ottawa Quality Assessment Form were used by two authors independently to assess the risk of bias (RoB). Statistical analysis was performed by Review Manager 5.3. The eight eligible trials were reviewed and included in qualitative synthesis. Four studies reported the overall time of leveling and alignment (OLAT, days), enabling a synthesizing of the data. The meta-analysis results showed that LLLT significantly reduced the overall time of leveling and alignment compared to control group (MD=-30.36, 95% CI range -41.50 to -19.22, P<0.0001), with moderate heterogeneity (χ2=4.10, P=0.25, I2=27%). Based on the data available, statistically significant evidence with moderate risk of bias suggests that LLLT may have a positive effect on accelerating dental alignment. However, due to the differences in intervention strategy and evaluating method, the conclusions should be interpreted with caution.

A Lesson of Immunosuppression in Renal Transplant: Retreat or Hold?

Background: Aiming at understanding whether there are cases of near-tolerance among long-term surviving kidney transplant recipients in our center, or even operant tolerance can be attempted based on their immune status, we analyzed changes of immune cell subsets and cytokines in various groups, and evaluated immune status of long-term survival recipients. Methods: A real-world, observational, retrospective cohort study was conducted in our hospital. Twenty-eight long-term recipients were selected as study subjects, 15 recent postoperative stable recipients, and 15 healthy subjects as controls. T and B lymphocyte subsets, MDSCs, and cytokines were detected and analyzed. Results: Treg/CD4 T cells, total B and B10 cells in long-term and recent renal recipients were lower than healthy controls (HC). The level of IFN-γ and IL-17A in long-term survival patients was obviously higher than that in recent postoperative stable recipients and HC, while TGF-ß1 level was significantly lower in long-term survival group than in short-term postoperative group and HC. Notably, compared with short-term recipients, it has been found that the IL-6 level in both positive and negative HLA groups were obviously lower (all P<0.05). In the long-term survival group, 43% of recipients were positive for urinary protein and 50% were positive for HLA antibody. Conclusion: This "real-world" study validates the findings of real status of long-term survival recipients observed in clinical trials. Contrary to a state of proper tolerance as expected, the group recipients in long-term survival were accompanied by the increased indicators of immune response, while those related to immune tolerance were not significantly increased. Long-term survival recipients with stable renal function may be in an immune equilibrium state where immunosuppression and rejection coexist under the action of low-intensity immune agents. If immunosuppressive agents are reduced or even removed, rejection may occur.

[Application of microneedle-assisted percutaneous drug delivery system in treatment of rheumatoid arthritis:a review].

Rheumatoid arthritis(RA) is a chronic degenerative joint disease characterized by inflammation. Due to the complex causes, no specific therapy is available. Non-steroidal anti-inflammatory agents and corticosteroids are often used(long-term, oral/injection) to interfere with related pathways for reducing inflammatory response and delaying the progression of RA, which, however, induce many side effects. Microneedle, an emerging transdermal drug delivery system, is painless and less invasive and improves drug permeability. Thus, it is widely used in the treatment of RA and is expected to be a new strategy in clinical treatment. This paper summarized the application of microneedles in the treatment of RA, providing a reference for the development of new microneedles and the expansion of its clinical application.

Unsymmetrically Chlorinated Non-Fused Electron Acceptor Leads to High-Efficiency and Stable Organic Solar Cells.

Searching the cost-effective organic semiconductors is strongly needed in order to facilitate the practice of organic solar cells (OSCs), yet to be fulfilled. Herein, we have succeeded in developing two non-fused ring electron acceptors (NFREAs), leading to the highest efficiency of 16.2 % for the NFREA derived OSCs. These OSCs exhibit the superior operational stabilities under one sun equivalent illumination without ultraviolet (UV) filtration. It is revealed that the modulation of halogen substituents on aromatic side chains, as the new structural tool to tune the intermolecular interaction and optoelectronic properties of acceptors, not only promotes the interlocked tic-tac-toe frame of three-dimensional stacks in solid, but also improves charge dynamics of acceptors to enable high-performance and stable OSCs.

Hydrogen Sulfide Biology and Its Role in Cancer.

Hydrogen sulfide (H2S) is an endogenous biologically active gas produced in mammalian tissues. It plays a very critical role in many pathophysiological processes in the body. It can be endogenously produced through many enzymes analogous to the cysteine family, while the exogenous source may involve inorganic sulfide salts. H2S has recently been well investigated with regard to the onset of various carcinogenic diseases such as lung, breast, ovaries, colon cancer, and neurodegenerative disorders. H2S is considered an oncogenic gas, and a potential therapeutic target for treating and diagnosing cancers, due to its role in mediating the development of tumorigenesis. Here in this review, an in-detail up-to-date explanation of the potential role of H2S in different malignancies has been reported. The study summarizes the synthesis of H2S, its roles, signaling routes, expressions, and H2S release in various malignancies. Considering the critical importance of this active biological molecule, we believe this review in this esteemed journal will highlight the oncogenic role of H2S in the scientific community.

Effects of individualized positive end-expiratory pressure combined with recruitment maneuver on intraoperative ventilation during abdominal surgery: a systematic review and network meta-analysis of randomized controlled trials.

Low tidal volume ventilation strategy may lead to atelectasis without proper positive end-expiratory pressure (PEEP) and recruitment maneuver (RM) settings. RM followed by individualized PEEP was a new method to optimize the intraoperative pulmonary function. We conducted a systematic review and network meta-analysis of randomized clinical trials to compare the effects of individualized PEEP + RM on intraoperative pulmonary function and hemodynamic with other PEEP and RM settings. The primary outcomes were intraoperative oxygenation index and dynamic compliance, while the secondary outcomes were intraoperative heart rate and mean arterial pressure. In total, we identified 15 clinical trials containing 36 randomized groups with 3634 participants. Ventilation strategies were divided into eight groups by four PEEP (L: low, M: moderate, H: high, and I: individualized) and two RM (yes or no) settings. The main results showed that IPEEP + RM group was superior to all other groups regarding to both oxygenation index and dynamic compliance. LPEEP group was inferior to LPEEP + RM, MPEEP, MPEEP + RM, and IPEEP + RM in terms of oxygenation index and LPEEP + RM, MPEEP, MPEEP + RM, HPEEP + RM, IPEEP, and IPEEP + RM in terms of dynamic compliance. All comparisons were similar for secondary outcomes. Our analysis suggested that individualized PEEP and RM may be the optimal low tidal volume ventilation strategy at present, while low PEEP without RM is not suggested.

[Mechanism of Linderae Radix against gastric cancer based on network pharmacology and in vitro experimental validation].

The present study explored the main active ingredients and the underlying mechanism of Linderae Radix the treatment of gastric cancer by network pharmacology, molecular docking, and in vitro cell experiments. TCMSP, OMIM and GeneCards database were used to obtain the active ingredients of Linderae Radix to predict the related targets of both Linderae Radix and gastric cancer. After screening the common potential action targets, the STRING database was used to construct the PPI network for protein interaction of the two common targets. Enrichment analysis of GO and KEGG by DAVID database. Based on STRING and DAVID platform data, Cytoscape software was used to construct an "active ingredient-target" network and an "active ingredient-target-pathway" network. Molecular docking was performed using the AutoDock Vina to predict the binding of the active components to the key action targets, and finally the key targets and pathways were verified in vitro. According to the prediction results, there were 9 active components, 179 related targets of Radix Linderae, 107 common targets of Linderae Radix and gastric cancer, 693 biological processes, 57 cell compositions, and 129 molecular functions involved in the targets, and 161 signaling pathways involved in tumor antigen p53, hypoxia-indu-cible factor 1, etc. Molecular docking results showed that the core component, jimadone, had high binding activity with TP53. Finally, in an in vitro experiment, the screened radix linderae active ingredient gemmadone is used for preliminarily verifying the core targets and pathways of the human gastric cancer cell SGC-7901, The results showed that germacrone could significantly inhibit the proliferation of gastric cancer cells and induce the apoptosis of SGC-7901 by regulating the expression of p53, Bax, Bcl-2 and other key proteins. In summary, Radix Linderae can control the occurrence and development of gastric cancer through multi-components, multi-targets and multi-pathways, which will provide theoretical basis for further clinical discussion on the mechanism of Radix Linderae in treating gastric cancer.

Multifaceted behavior of PEST sequence enriched nuclear proteins in cancer biology and role in gene therapy.

The amino acid sequence enriched with proline (P), glutamic acid (E), serine (S), and threonine (T) (PEST) is a signal-transducing agent providing unique features to its substrate nuclear proteins (PEST-NPs). The PEST motif is responsible for particular posttranslational modifications (PTMs). These PTMs impart distinct properties to PEST-NPs that are responsible for their activation/inhibition, intracellular localization, and stability/degradation. PEST-NPs participate in cancer metabolism, immunity, and protein transcription as oncogenes or as tumor suppressors. Gene-based therapeutics are getting the attention of researchers because of their cell specificity. PEST-NPs are good targets to explore as cancer therapeutics. Insights into PTMs of PEST-NPs demonstrate that these proteins not only interact with each other but also recruit other proteins to/from their active site to promote/inhibit tumors. Thus, the role of PEST-NPs in cancer biology is multivariate. It is hard to obtain therapeutic objectives with single gene therapy. An especially designed combination gene therapy might be a promising strategy in cancer treatment. This review highlights the multifaceted behavior of PEST-NPs in cancer biology. We have summarized a number of studies to address the influence of structure and PEST-mediated PTMs on activation, localization, stability, and protein-protein interactions of PEST-NPs. We also recommend researchers to adopt a pragmatic approach in gene-based cancer therapy.

Agricultural Plastic Pollution in China: Generation of Plastic Debris and Emission of Phthalic Acid Esters from Agricultural Films.

Agricultural plastic films have been proven highly advantageous, but they also cause pollution of plastic debris and associated chemicals. Phthalates (phthalic acid esters, PAEs), an important additive of agricultural films, can be released and contaminate the environment. Here, we analyzed the agricultural plastic usage and assessed plastic debris in China and developed a method to estimate PAE emissions from agricultural films. Additionally, the environmental fate of PAEs was evaluated using a fugacity-based multimedia model. The agricultural plastic film usage in China in 2017 was 2,528,600 tons. After agricultural film recycling and water erosion, the plastic debris amount was estimated as 465,016 tons. The water erosion process carried 4329 tons of plastic debris into the aquatic environment. During its lifetime, the agricultural film released a total of 91.5 tons of two typical types of PAEs. PAEs from the mulching film would mostly be removed through degradation, while those from the greenhouse film accumulate in vegetables. Populated regions exhibited more serious PAE pollution in vegetables but with no immediate health risks. The model was well evaluated using comparable measured concentrations and uncertainty analysis based on the Monte Carlo method. The findings from this study demonstrate the serious agricultural plastic pollution problem and associated PAE contamination in China.

MicroRNA-93-5p participates in type 2 diabetic retinopathy through targeting Sirt1.

OBJECTIVE: To investigate the role of miR-93-5p in rats with type 2 diabetic retinopathy (DR) through targeting Sirt1. METHODS: The targeting correlation between miR-93-5p and Sirt1 was validated by dual-luciferase reporter gene assay. Type 2 diabetes mellitus (T2DM) rat models were received intravitreal injection of antagomir NC (negative control), miR-93-5p antagomir, miR-93-5p agomir and/or recombinant Sirt1, followed by observation of pathological changes in retina via HE staining. Besides, retinal vascular permeability was determined by fluorescein isothiocyanate-bovine serum albumin (FITC-BSA), while the retinal vasculature was observed through retinal trypsin digestion. Expression of miR-93-5p and Sirt1 was measured by qRT-PCR and Western blotting, while the levels of VEGF, proinflammatory cytokines and anti-oxidative indicators were determined using corresponding kits. RESULTS: MiR-93-5p could target Sirt1 as analyzed by the luciferase reporter gene assay. Rats in the T2DM group presented the up-regulation of miR-93-5p and down-regulation of Sirt1 in the retina, and miR-93-5p inhibition could up-regulate Sirt1 expression in the T2DM rats. Recombinant Sirt1 decreased retinal vascular permeability and acellular capillaries with improved pathological changes in retina from T2DM rats, which was abolished by miR-93-5p agomir. Moreover, miR-93-5p inhibition or Sirt1 overexpression decreased the levels of VEGF and proinflammatory cytokines while enhancing the activity of anti-oxidative indicators. However, indicators above had no significant differences between T2DM group and T2DM + agomir + Sirt1 group. CONCLUSION: MiR-93-5p, via targeting Sirt1, could affect the vascular permeability and acellular capillaries and mitigate the inflammation and oxidative stress in the retinas, which may play a critical role in DR.

Synthesis and evaluation of 1,2,4-oxadiazole derivatives as potential anti-inflammatory agents by inhibiting NF-κB signaling pathway in LPS-stimulated RAW 264.7 cells.

In this study, a series of compounds with 1,2,4-oxadiazole core was designed and synthesized for the optimization of JC01, an anti-inflammatory hit identified from our in-house compound library using NF-κB pathway luciferase assay and NO production assay. All the synthetic compounds 1-29 have been screened for their anti-inflammatory effects by evaluating their inhibition against LPS-induced NO release, and compound 17 exhibited the highest activity. Western blotting and immunofluorescence analysis revealed that 17 prominently inhibited LPS-induced activation of NF-κB in RAW264.7 cells and blocked the phosphorylation of p65. Consistent with these results, it was found that 17 prevented the nuclear translocation of NF-κB induced by LPS. These data highlighted 17 as a promising anti-inflammatory agent by inhibiting NF-κB activity.

Intact Arabidopsis RPB1 functions in stem cell niches maintenance and cell cycling control.

Plant meristem activity depends on accurate execution of transcriptional networks required for establishing optimum functioning of stem cell niches. An Arabidopsis mutant card1-1 (constitutive auxin response with DR5:GFP) that encodes a truncated RPB1 (RNA Polymerase II's largest subunit) with shortened C-terminal domain (CTD) was identified. Phosphorylation of the CTD repeats of RPB1 is coupled to transcription in eukaryotes. Here we uncover that the truncated CTD of RPB1 disturbed cell cycling and enlarged the size of shoot and root meristem. The defects in patterning of root stem cell niche in card1-1 indicates that intact CTD of RPB1 is necessary for fine-tuning the specific expression of genes responsible for cell-fate determination. The gene-edited plants with different CTD length of RPB1, created by CRISPR-CAS9 technology, confirmed that both the full length and the DK-rich tail of RPB1's CTD play roles in the accurate transcription of CYCB1;1 encoding a cell-cycle marker protein in root meristem and hence participate in maintaining root meristem size. Our experiment proves that the intact RPB1 CTD is necessary for stem cell niche maintenance, which is mediated by transcriptional regulation of cell cycling genes.

Insulin-like growth factor binding protein related protein 1 knockdown attenuates hepatic fibrosis via the regulation of MMPs/TIMPs in mice.

BACKGROUND: Previous research suggested that insulin-like growth factor binding protein related protein 1 (IGFBPrP1), as a novel mediator, contributes to hepatic fibrogenesis. Matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) play an essential role in hepatic fibrogenesis by regulating homeostasis and remodeling of the extracellular matrix (ECM). However, the interaction between IGFBPrP1 and MMP/TIMP is not clear. The present study was to knockdown IGFBPrP1 to investigate the correlation between IGFBPrP1 and MMP/TIMP in hepatic fibrosis. METHODS: Hepatic fibrosis was induced by thioacetamide (TAA) in mice. Knockdown of IGFBPrP1 expression by ultrasound-targeted microbubble destruction-mediated CMB-shRNA-IGFBPrP1 delivery, or inhibition of the Hedgehog (Hh) pathway by cyclopamine treatment, was performed in TAA-induced liver fibrosis mice. Hepatic fibrosis was determined by hematoxylin and eosin and Sirius red staining. Hepatic expression of IGFBPrP1, α-smooth muscle actin (α-SMA), transforming growth factor ß 1 (TGFß1), collagen I, MMPs/TIMPs, Sonic Hedgehog (Shh), and glioblastoma family transcription factors (Gli1) were investigated by immunohistochemical staining and Western blotting analysis. RESULTS: We found that hepatic expression of IGFBPrP1, TGFß1, α-SMA, and collagen I were increased longitudinally in mice with TAA-induced hepatic fibrosis, concomitant with MMP2/TIMP2 and MMP9/TIMP1 imbalance and Hh pathway activation. Knockdown of IGFBPrP1 expression, or inhibition of the Hh pathway, reduced the hepatic expression of IGFBPrP1, TGFß1, α-SMA, and collagen I and re-established MMP2/TIMP2 and MMP9/TIMP1 balance. CONCLUSIONS: Our findings suggest that IGFBPrP1 knockdown attenuates liver fibrosis by re-establishing MMP2/TIMP2 and MMP9/TIMP1 balance, concomitant with the inhibition of hepatic stellate cell activation, down-regulation of TGFß1 expression, and degradation of the ECM. Furthermore, the Hh pathway mediates IGFBPrP1 knockdown-induced attenuation of hepatic fibrosis through the regulation of MMPs/TIMPs balance.

Correlation between 18F-FDG PET CT SUV and symptomatic or asymptomatic pulmonary tuberculosis.

OBJECTIVE: To explore the difference of 18F-FDG PET/CT images between the symptomatic and asymptomatic pulmonary tuberculosis, as well as the correlation between the standard uptake value (SUV) and the symptomatic/asymptomatic pulmonary tuberculosis. METHODS: A study dataset of 57 pulmonary tuberculosis cases was retrospectively assembled and analyzed. Among these cases, 30 were diagnosed having symptomatic pulmonary tuberculosis and 27 were asymptomatic pulmonary tuberculosis. PET/CT was performed in all 57 cases. The clinical data, CT images and PET/CT radioactive uptake data were analyzed using statistical data analysis software. RESULTS: All 57 cases showed radioactively high uptake, with the maximum standard uptake value (SUVmax) of the lesion ranging from 1.60 to 27.30 and a mean value of 6.63±4.82. The symptomatic cases had an SUVmax of 8.76±4.97 and the asymptomatic cases had an SUVmax of 4.27±3.39. The SUVmax as well as singular or multiple lesions showed statistical differences between symptomatic and asymptomatic cases. CONCLUSION: The symptomatic pulmonary tuberculosis cases show significantly higher SUVmax than the asymptomatic cases. Based on the criteria of SUVmax greater than 2.0 to define active lesions, 100% of symptomatic cases might have active lesions while 70.4% of asymptomatic cases might have active lesions. Therefore, focused attention should be clinically paid on the asymptomatic cases of pulmonary tuberculosis to avoid miss diagnosis and delayed treatment.

[Effect of genetic modifiers on the clinical severity of ß-thalassemia].

ß-thalassemia (ß-thal) is a fatal and disabling inherited blood disorder with diverse phenotypes. The same or similar genotype of ß-thal can manifest variable clinical severities. It is the hotspot and emphasis in the field of hematopathy and genetic diseases to explore genetic modifiers that influence the phenotype of ß-thal. This review illustrates the deteriorating and amelioratig modifiers from two aspects: genotypes of α-globin and quantitative trait locus of fetal hemoglobin (Hb F). Variations of transcription factors which reactive the γ-globin gene expression and ß-globin cluster cis-acting elements were introduced emphatically. Finally, clinical applications and future development prospects of ß-thal genetic modifiers are introduced by examples.