Afterglow/Photothermal Bifunctional Polymeric Nanoparticles for Precise Postbreast-Conserving Surgery Adjuvant Therapy and Early Recurrence Theranostic.

Adjuvant whole-breast radiotherapy is essential for breast cancer patients who adopted breast-conserving surgery (BCS) to reduce the risk of local recurrences, which however suffer from large-area and highly destructive ionizing radiation-induced adverse events. To tackle this issue, an afterglow/photothermal bifunctional polymeric nanoparticle (APPN) is developed that utilizes nonionizing light for precise afterglow imaging-guided post-BCS adjuvant second near-infrared (NIR-II) photothermal therapy. APPN consists of a tumor cell targeting afterglow agent, which is doped with a NIR dye as an afterglow initiator and a NIR-II light-absorbing semiconducting polymer as a photothermal transducer. Such a design realizes precise afterglow imaging-guided NIR-II photothermal ablation of minimal residual breast tumor foci after BCS, thus achieving complete inhibition of local recurrences. Moreover, APPN enables early diagnosis and treatment of local recurrence after BCS. This study thus provides a nonionizing modality for precision post-BCS adjuvant therapy and early recurrence theranostic.

Acetyltransferase P300 Regulates Glucose Metabolic Reprogramming through Catalyzing Succinylation in Lung Cancer.

Aberrant protein post-translational modification is a hallmark of malignant tumors. Lysine succinylation (Ksucc) plays a vital role in cell energy metabolism in various cancers. However, whether succinylation can be catalyzed by acetyltransferase p300 remains unclear. In this study, we unveiled that p300 is a "writer" for succinylation, and p300-mediated Ksucc promotes cell glycometabolism in lung adenocarcinoma (LUAD). Specifically, our succinylome data revealed that EP300 deficiency leads to the systemic reduction of Ksucc, and 79.55% of the p300-succinylated proteins were found in the cytoplasm, which were primarily enriched in the carbohydrate metabolism process. Interestingly, deleting EP300 led to a notable decrease in Ksucc levels on several glycolytic enzymes, especially Phosphoglycerate Kinase 1 (PGK1). Mutation of the succinylated site of PGK1 notably hindered cell glycolysis and lactic acid excretion. Metabolomics in vivo indicated that p300-caused metabolic reprogramming was mainly attributed to the altered carbohydrate metabolism. In addition, 89.35% of LUAD patients exhibited cytoplasmic localization of p300, with higher levels in tumor tissues than adjacent normal tissues. High levels of p300 correlated with advanced tumor stages and poor prognosis of LUAD patients. Briefly, we disclose the activity of p300 to catalyze succinylation, which contributes to cell glucose metabolic reprogramming and malignant progression of lung cancer.

Metabolic checkpoints and novel approaches for immunotherapy against cancer.

While immunotherapy has achieved unprecedented success in conquering cancer, the majority of patients develop primary or acquired resistance to immunotherapy, largely in part due to the complicated metabolic networks in the tumor microenvironment. The microenvironmental metabolic networks are woven by a set of metabolic checkpoints, and accumulating evidence indicates that these metabolic checkpoints orchestrate antitumor immunity and immunotherapy. Metabolic checkpoints can regulate T cell development, differentiation and function, orchestrate metabolic competition between tumor cells and infiltrating T cells, and respond to the metabolic stress imposed on the infiltrating T cells. Furthermore, metabolic checkpoints and pathways can modulate the expression profiles of immune checkpoint receptors and ligands and vice versa. Therefore, repurposing interventions targeting metabolic checkpoints might synergize with immunotherapy, and promising approaches to reprogram the metabolic environment are much more warranted. In this review, we summarize recent researches on the metabolic checkpoints and discuss how these metabolic checkpoints regulate antitumor immunity and the promising approaches to modulate these metabolic checkpoints in the combination therapy. A comprehensive and objective understanding of the metabolic checkpoints might help the research and development of novel approaches to antitumor immunotherapy.

Intermittent fasting reduces neuroinflammation in intracerebral hemorrhage through the Sirt3/Nrf2/HO-1 pathway.

BACKGROUND: Inflammation contributes to the poor prognosis of intracerebral hemorrhage (ICH). Intermittent fasting (IF) has been shown to be protective against inflammation in multiple pathogenic processes. In the present study, we aimed to investigated the beneficial effects of IF in attenuating neuroinflammation and neurological deficits in a mouse model of ICH and to investigate the underlying mechanism. METHODS: ICH was modeled by intrastriatal injection of autologous blood and IF was modeled by every-other-day feeding in male control mice (C57BL/6), mice with and microglia specific knockout Sirt3f/f;Cx3cr1-Cre (Sirt3 cKO), and Sirt3f/f (wild-type) mice. Brain tissues and arterial blood were harvested at 1, 3, 7 and 28 days after ICH for immunohistochemistry analysis of Iba-1, DARPP-32 and HO-1, morphological analysis by HE staining and inflammatory factor release tests by ELISA. Neurological functions were approached by corner test and cylinder test. Fluorescent double-labeled staining of Iba-1 with CD16, Arg1 or Sirt3 was used to provide direct image of co-expression of these molecules in microglia. TUNEL, cleaved caspase-3 and Nissl staining was performed to evaluate cellular injuries. RESULTS: IF alleviated neurological deficits in both acute and chronic phases after ICH. Morphologically, IF enhanced hematoma clearance, reduced brain edema in acute phase and attenuated striatum atrophy in chronic phase. In addition, IF decreased the numbers of TUNEL+ cells and increased Nissl+ neuron number at day 1, 3 and 7 after ICH. IF suppressed CD16+Iba-1+ microglia activation at day 3 after ICH and reduced inflammatory releases, such as IL-1ß and TNF-α. The above effects of IF were attenuated by microglia Sirt3 deletion partly because of an inhibition of Nrf2/HO-1 signaling pathway. Interestingly, IF increased Iba-1+ microglia number at day 7 which mainly expressed Arg1 while decreased the proinflammatory factor levels. In mice with microglia-specific Sirt3 deletion, the effects of IF on Iba-1+ microglia activation and anti-inflammatory factor expressions were attenuated when compared with wild-type Sirt3f/f mice. CONCLUSIONS: IF protects against ICH by suppressing the inflammatory responses via the Sirt3/Nrf2/HO-1 pathway.

Integrative and Comprehensive Pan-Cancer Analysis of Lymphocyte-Specific Protein Tyrosine Kinase in Human Tumors.

Lymphocyte-specific protein tyrosine kinase (LCK) is common in a variety of hematologic malignancies but comparatively less common in solid tumors. This study aimed to explore the potential diagnostic and prognostic value of LCK across tumors through integrative and comprehensive pan-cancer analysis, as well as experimental validation. Multiple databases were used to explore the expression, alteration, prognostic value, association with immune infiltration, and potential functional pathways of LCK in pan-cancers. The results were further validated by western blotting and qPCR of patient samples as well as tumor cell lines. High LCK expression typically represents a better prognosis. Notably, drug sensitivity prediction of LCK identified P-529 as a candidate for drug development. Gene Annotations (GO) and KEGG analyses showed significant enrichment of PD-L1 and the T-cell receptor pathway. The results from patient samples and tumor cell lines confirmed these conclusions in LIHC. In conclusion, LCK is differentially expressed in multiple tumors and normal tissues. Further analysis highlighted its association with prognostic implications, pan-cancer genetic alterations, and immune signatures. Our data provide evidence for a diagnostic marker of LCK and the possible use of LCK as a target for the treatment of tumors.

Policy, technical change, and environmental efficiency: Evidence of China's power system from dynamic and spatial perspective.

Feed-in tariff (FIT) and renewable portfolio standard (RPS) policies have been implemented to facilitate wind and solar power technologies with the aim of achieving sustainable development in power system. It is essential to study how efficient these policies are in accelerating technical progress and how efficient the power system is in balancing development and environmental protection. Dynamic network data envelopment analysis and the global Malmquist productivity index are first employed to study the environmental efficiency and technical progress, after which a dynamic spatial Durbin model is applied to analyze the impact of policies on technical progress. The results reveal that both FIT and RPS lead to technical progress which is the main driving force in environmental efficiency improvement, but that RPS performs better than FIT. From a spatial perspective, the adjacent regions usually show similar characteristics in technical progress. Therefore, future policy design should carefully consider the regional agglomeration effects and should effectively strengthen the implementation of RPS policy.

CD147 promotes DNA damage response and gemcitabine resistance via targeting ATM/ATR/p53 and affects prognosis in pancreatic cancer.

The acquisition of chemoresistance is a major clinical challenge for pancreatic cancer (PC) treatment. Chemoresistance is largely attributed to aberrant DNA damage repair. However, the underlying mechanisms of chemoresistance in pancreatic cancer remain unclear. Here, we showed that CD147 was strongly correlated to DNA damage response (DDR) indices and poor prognosis in pancreatic ductal adenocarcinoma (PDAC) patients. CD147 knockdown or monoclonal antibodies improved the killing effects of gemcitabine in gemcitabine resistant cells, exhibiting reduced activation of ATM/p53. Moreover, we found the interaction of CD147 with ATM, ATR and p53, which was augmented in gemcitabine resistant cells. High CD147/p-ATM/p-ATR/p-p53 cytoplasmic expression associated with poor survival of PC patients. Our studies thus identify CD147 as a critical player in DDR programing that affects gemcitabine therapeutic outcomes of pancreatic cancer patients.

CNOT3 contributes to cisplatin resistance in lung cancer through inhibiting RIPK3 expression.

Chemotherapeutic resistance always results in poor clinical outcomes of cancer patients and its intricate mechanisms are large obstacles in overcoming drug resistance. CCR4-NOT transcription complex subunit 3 (CNOT3), a post-translational regulator, is suggested to be involved in cancer development and progression. However, its role in chemotherapeutic resistance is not well understood. In this study, after screening the CNOT3 mRNA in a cancer microarray database called Oncomine and examining the expression levels of CNOT3 mRNA in normal tissues and lung cancer tissues, we found that CNOT3 was up-regulated in lung cancer tissues. Besides, its high-expression was associated with poor prognosis of lung cancer patients. We also found higher expression level of CNOT3 and lower expression level of receptor-interacting protein kinase 3 (RIPK3) in cisplatin-resistant A549 (A549/DDP) cells, and knocking down CNOT3 expression could sensitize A549/DDP cells to cisplatin-induced apoptosis. We demonstrated that CNOT3 depletion up-regulated the expression level of RIPK3 and the enhanced apoptosis was mediated by the elevated RIPK3 to further trigger Caspase 8 activation. Taken together, our results reveal a role of CNOT3 in cisplatin resistance of lung cancer and provide a potential target for lung cancer therapy.

N-glycosylation by N-acetylglucosaminyltransferase V enhances the interaction of CD147/basigin with integrin ß1 and promotes HCC metastasis.

While the importance of protein N-glycosylation in cancer cell migration is well appreciated, the precise mechanisms by which N-acetylglucosaminyltransferase V (GnT-V) regulates cancer processes remain largely unknown. In the current study, we report that GnT-V-mediated N-glycosylation of CD147/basigin, a tumor-associated glycoprotein that carries ß1,6-N-acetylglucosamine (ß1,6-GlcNAc) glycans, is upregulated during TGF-ß1-induced epithelial-to-mesenchymal transition (EMT), which correlates with tumor metastasis in patients with hepatocellular carcinoma (HCC). Interruption of ß1,6-GlcNAc glycan modification of CD147/basigin decreased matrix metalloproteinase (MMP) expression in HCC cell lines and affected the interaction of CD147/basigin with integrin ß1. These results reveal that ß1,6-branched glycans modulate the biological function of CD147/basigin in HCC metastasis. Moreover, we showed that the PI3K/Akt pathway regulates GnT-V expression and that inhibition of GnT-V-mediated N-glycosylation suppressed PI3K signaling. In summary, ß1,6-branched N-glycosylation affects the biological function of CD147/basigin and these findings provide a novel approach for the development of therapeutic strategies targeting metastasis. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Multiband bonding/anti-boding interaction and selective electric field confinement in the complementary metamaterial.

We report the experimental and theoretical study on the complementary planar metamaterial with asymmetrical air nanorods. Three high-quality samples are fabricated by the focused ion beam technique. Multi-band Fano-like resonances and selective electric field confinement in the visible-near infrared range are presented and well explained by the bonding/anti-boding and coupled mode theories of plasmonic resonators.

Rab22a enhances CD147 recycling and is required for lung cancer cell migration and invasion.

Rab22a is a member of the Ras-related small GTPase family, which plays a key role in regulating the recycling of cargo proteins entering cells through clathrin-independent endocytosis (CIE). Rab22a is overexpressed in different cancer types, including liver cancer, malignant melanoma, ovarian cancer and osteosarcoma. However, its oncogenic role remains unknown. In this study, we found that silencing of Rab22a suppressed the migration and invasion of lung cancer cells. Furthermore, Rab22a interacts with CD147, and knockdown of Rab22a blocks CD147 recycling and promotes CD147 degradation. Taken together, our findings indicate that Rab22a enhances recycling of CD147, which is required for lung cancer cell migration and invasion,and targeting CD147 recycling may be a rational strategy for lung cancer therapy.

Regulation of Akt/FoxO3a/Skp2 Axis Is Critically Involved in Berberine-Induced Cell Cycle Arrest in Hepatocellular Carcinoma Cells.

The maintenance of ordinal cell cycle phases is a critical biological process in cancer genesis, which is a crucial target for anti-cancer drugs. As an important natural isoquinoline alkaloid from Chinese herbal medicine, Berberine (BBR) has been reported to possess anti-cancer potentiality to induce cell cycle arrest in hepatocellular carcinoma cells (HCC). However, the underlying mechanism remains to be elucidated. In our present study, G0/G1 phase cell cycle arrest was observed in berberine-treated Huh-7 and HepG2 cells. Mechanically, we observed that BBR could deactivate the Akt pathway, which consequently suppressed the S-phase kinase-associated protein 2 (Skp2) expression and enhanced the expression and translocation of Forkhead box O3a (FoxO3a) into nucleus. The translocated FoxO3a on one hand could directly promote the transcription of cyclin-dependent kinase inhibitors (CDKIs) p21Cip1 and p27Kip1, on the other hand, it could repress Skp2 expression, both of which lead to up-regulation of p21Cip1 and p27Kip1, causing G0/G1 phase cell cycle arrest in HCC. In conclusion, BBR promotes the expression of CDKIs p21Cip1 and p27Kip1 via regulating the Akt/FoxO3a/Skp2 axis and further induces HCC G0/G1 phase cell cycle arrest. This research uncovered a new mechanism of an anti-cancer effect of BBR.

Out-of-plane focusing and manipulation of terahertz beams based on a silicon/copper grating covered by monolayer graphene.

We report new models for out-of-plane focusing and manipulation of terahertz beams based on a silicon/copper grating covered by monolayer graphene. Dependences of focusing and manipulation of terahertz beams on the chemical potential and scattering rate of graphene are investigated. Based on the graphene/silicon grating model, we demonstrate that the focal distance and intensity are sensitively influenced by the chemical potential. Based on the graphene/copper grating model, we show how 2 to 1 and 3 to 1 modulation of terahertz beams can be efficiently realized through tuning the chemical potential of graphene. These tunable beam focusing and manipulation effects are well explained by the diffraction theory of optical images and the surface plasmon polariton theory of graphene. Our proposed devices are of compact structures, high electro-optical tunability and good repeatability, and they are expected to have prospective applications in terahertz communications, imaging, sensing, and so on.

F-Box Protein FBXO22 Mediates Polyubiquitination and Degradation of CD147 to Reverse Cisplatin Resistance of Tumor Cells.

Drug resistance remains a major clinical obstacle to successful treatment of cancer. As posttranslational modification is becoming widely recognized to affect the function of oncoproteins, targeting specific posttranslational protein modification provides an attractive strategy for anticancer drug development. CD147 is a transmembrane glycoprotein contributing to chemo-resistance of cancer cells in a variety of human malignancies. Ubiquitination is an important posttranslational modification mediating protein degradation. Degradation of oncoproteins, CD147 included, emerges as an attractive alternative for tumor inhibition. However, the ubiquitination of CD147 remains elusive. Here in this study, we found that deletion of the CD147 intracellular domain (CD147-ICD) prolonged the half-life of CD147 in HEK293T cells, and we identified that CD147-ICD interacts with FBXO22 using mass spectrometry and Western blot. Then, we demonstrated that FBXO22 mediates the polyubiquitination and degradation of CD147 by recognizing CD147-ICD. While knocking down of FBXO22 prolonged the half-life of CD147 in HEK293T cells, we found that FBXO22 regulates CD147 protein turnover in SMMC-7721, Huh-7 and A549 cells. Moreover, we found that the low level of FBXO22 contributes to the accumulation of CD147 and thereafter the cisplatin resistance of A549/DDP cells. To conclude, our study demonstrated that FBXO22 mediated the polyubiquitination and degradation of CD147 by interacting with CD147-ICD, and CD147 polyubiquitination by FBXO22 reversed cisplatin resistance of tumor cells.

CD147 promotes cell motility via upregulation of p190-B RhoGAP in hepatocellular carcinoma.

BACKGROUND: The acquisition of inappropriate migratory feature is crucial for tumor metastasis. Rho-family GTPases including RhoA are molecular switches that play critical roles in regulating cell movement. We investigated the molecular mechanism underlying CD147 induced RhoA deactivation in hepatocellular carcinoma (HCC) cells. METHODS: Wound-healing assay was performed to study the cell motility. Analysis of RhoA activation in living cells was conducted using RhoA biosensor. Changes in the expression of certain genes were determined by quantitative real-time PCR. The expression of proteins was evaluated by Western blot. Cytoskeleton reorganization and focal adhesion formation were observed by immunofluorescence staining. Further investigation on the correlation between CD147 and p190-B RhoGAP (p190-B) in HCC tissues was performed by immunological histological chemistry analysis. RESULTS: CD147 promoted cell movement and suppressed RhoA activation. p190-B, a negative regulator of RhoA activity, was upregulated by CD147 at both mRNA and protein levels. This regulatory relationship was further confirmed by analyzing the expression pattern of CD147 and p190-B in human HCC tissues. Silencing of p190-B caused the increased formation of stress fiber and focal adhesion and blunted the impact of CD147 overexpression on cell movement, indicating that the regulatory effect of CD147 on cell movement is mediated, at least partially, by p190-B. CONCLUSIONS: These findings indicated that p190-B, a negative regulator of RhoA, is positively regulated by CD147 and contributes to the regulation of cell movement in HCC. CD147 plays critical roles in the motility of cancer cells and may be therefore a valuable drug target for anti-cancer therapy.

Dominant Suppression of ß1 Integrin by Ectopic CD98-ICD Inhibits Hepatocellular Carcinoma Progression.

Hepatocellular carcinoma (HCC) is currently the third most common cause of cancer-related death in the Asia-Pacific region. Our previous work showed that knockdown of CD98 significantly inhibits malignant HCC cell phenotypes in vitro and in vivo. The level of CD98 in the membrane is tightly regulated to mediate complex processes associated with cell-cell communication and intracellular signaling. In addition, the intracellular domain of CD98 (CD98-ICD) seems to be of vital importance for recycling CD98 to the membrane after it is endocytosed. The intracellular and transmembrane domains of CD98 associate with ß-integrins (primarily ß1 but also ß3), and this association is essential for CD98 mediation of integrin-like signaling and complements dominant suppression of ß1-integrin. We speculated that isolated CD98-ICD would similarly suppress ß1-integrin activation and inhibit the malignant behaviors of cancer cells. In particular, the exact role of CD98-ICD has not been studied independently in HCC. In this study, we found that ectopic expression of CD98-ICD inhibited the malignant phenotypes of HCC cells, and the mechanism possibly involves ß1-integrin suppression. Moreover, the expression levels of CD98, ß1-integrin-A (the activated form of ß1-integrin) and Ki-67 were significantly increased in HCC tissues relative to those of normal liver tissues. Therefore, our preliminary study indicates that ectopic CD98-ICD has an inhibitory role in the malignant development of HCC, and shows that CD98-ICD acts as a dominant negative mutant of CD98 that attenuates ß1-integrin activation. CD98-ICD may emerge as a promising candidate for antitumor treatment.

CD147 promotes reprogramming of glucose metabolism and cell proliferation in HCC cells by inhibiting the p53-dependent signaling pathway.

BACKGROUND & AIMS: Cancer cells exhibit the reprogrammed metabolism characterized by high level of glycolysis even in the presence of oxygen. Aerobic glycolysis, known as the Warburg effect, supplies cancer cells with the substrates required for biomass generation. To date, several intracellular signaling mediators have been identified in metabolic regulation of cancer cells. However, it remains largely ambiguous how molecules on the cell surface are involved in regulation of cancer metabolism. METHODS: In the current study, we established several HCC cell lines differing in their CD147 (a typical transmembrane glycoprotein) expression status by zinc-finger nuclease and RNAi techniques. Then, we systematically investigated the role of CD147 in the regulation of the Warburg effect in HCC cells and explored the underlying mechanism. RESULTS: We found that CD147 significantly contributed to the reprogramming of glucose metabolism in HCC cells through a p53-dependent way. CD147 facilitated the cell surface expression of MCT1 and lactate export, which led to activation of the PI3K/Akt/MDM2 pathway and thus increased p53 degradation. The gain/loss-of-function studies demonstrated that while CD147 promoted glycolysis, mediated by p53-dependent upregulation of GLUT1 and activation of PFKL, it inhibited mitochondrial biogenesis and functions, mediated by p53-dependent downregulation of PGC1α, TFAM, and p53R2. Additionally, proliferation of HCC cells was suppressed by blocking CD147 and/or MCT1, which resulted in down-regulation of glucose metabolism. CONCLUSIONS: We demonstrate that CD147 is a crucial regulator of glucose metabolism.

High GINS2 transcript level predicts poor prognosis and correlates with high histological grade and endocrine therapy resistance through mammary cancer stem cells in breast cancer patients.

GINS2, a subunit of the GINS complex, is overexpressed in lung adenocarcinoma and metastatic breast tumor; however, its prognostic power and possible molecular mechanisms in breast cancer (BC) remain unclear. In this study, we aimed to explore the function of GINS2 in BC. The association between GINS2 transcript level and the clinical outcome of BC patients were estimated using Kaplan-Meier plots, multivariate cox regression analysis, forest plots, and receiver operating characteristics curves. Gene set enrichment analysis (GSEA) was performed to explore the mechanisms underlying the effects of the GINS2 transcript. High GINS2 transcript level was correlated with poor relapse free survival (log-rank P ≤ 0.001 in six cohorts; forest plot: total n = 1,420, total RR = 1.72, 95% CI 1.45-2.03; multivariate cox regression analysis: n = 906, HR 2.36, 95% CI 1.88-2.97), and distant metastasis free survival (log-rank P < 0.01 in 3 cohorts; forest plot: total n = 691, total RR 1.91, 95% CI 1.36-2.67; multivariate cox regression analysis: n = 442, HR 2.43, 95% CI 1.70-3.47). BC patients with higher GINS2 transcript levels showed poorer tamoxifen efficacy in a dose-dependent manner. GINS2 expression was significantly downregulated under mutated p53-depleted condition in MDA-468 and MDA-MB-231 cells, upregulated in mammary cancer stem cells (MaCSCs) (P = 0.003), and correlated with upregulated genes in mammary stem cells (GSEA: P < 0.01). Our study, for the first time, demonstrates that GINS2 is an independent prognostic marker and is associated with lung metastasis, histological grade, and endocrine therapy resistance in BC patients, which may attribute to mutant p53 and MaCSCs.

Modulation of CD147-induced matrix metalloproteinase activity: role of CD147 N-glycosylation.

Degradation of the basement membrane by MMPs (matrix metalloproteinases) is one of the most critical steps in tumour progression. CD147 is a tumour-associated antigen that plays a key regulatory role for MMP activities. In the present study, mass spectrum analysis demonstrated that the purified native CD147 from human lung cancer tissue was N-glycosylated and contained a series of high-mannose and complex-type N-linked glycan structures. Moreover, native glycosylated CD147 existed exclusively as oligomers in solution and directly stimulated MMP production more efficiently than non-glycosylated prokaryotic CD147. The glycosylation site mutation results indicated that, among three N-glycan attachment sites, the N152Q mutants were retained in the endoplasmic reticulum and unfolded protein response signalling was activated. This improper intracellular accumulation impaired its MMP-inducing activity. Increased ß1,6-branching of N-glycans as a result of overexpression of GnT-V (N-acetylglucosaminyltransferase V) plays an important role in tumour metastasis. In the present study, we identified CD147 as a target protein of GnT-V and found that overexpression of GnT-V resulted in an elevated level of CD147 at the plasma membrane and in cell-conditioned medium, thereby increasing the induction of MMPs. The present study reveals the important role of N-glycosylation of CD147 in its biological function and implied that targeting aberrant ß1,6-branching of N-glycans on CD147 would be valuable for the development of novel therapeutic modalities against carcinoma.

Intravenous pretreatment with emulsified isoflurane preconditioning protects kidneys against ischemia/reperfusion injury in rats.

BACKGROUND: Emulsified isoflurane (EIso) is a novel intravenous general anesthetic, which can provide rapid anesthetic induction and recovery. EIso preconditioning could attenuate heart, lung and liver ischemia/reperfusion (I/R) injury. We tested the hypothesis that intravenous pretreatment with EIso would protect kidneys against I/R injury by inhibiting systemic inflammatory responses and improving renal antioxidative ability. METHODS: RATS WERE RANDOMLY DIVIDED INTO THESE SIX GROUPS: sham, I/R, intralipid, 1, 2 or 4 ml/kg EIso. Rats were subjected to 45 min left renal pedicle occlusion followed by 3 h reperfusion after right nephrectomy. Rat were treated with intravenous 8% EIso with 1, 2 or 4 ml/kg, or 30% intralipid with 2 ml/kg for 30 min before ischemia, respectively. After reperfusion, renal functional parameters, serum mediator concentrations and markers of oxidative stress in kidney tissues were determined, and renal histopathological analysis were performed. RESULTS: Serum creatinine, blood urea nitrogen, cystatin c, tumor necrosis factor-α, interleukin-6, and interleukin-10 concentrations were significantly increased after renal I/R as compared to the sham group. So was renal tissue MDA content and histological scores, but renal tissue SOD activity was decreased. Additionally, severe morphological damages were observed in these study groups. In contrast, 2 or 4 ml/kg EIso reduced serum creatinine, blood urea nitrogen, cystatin c, tumor necrosis factor-α, and interleukin-6 levels, decreased renal tissue MDA content and histological scores, increased serum interleukin-10 level and tissue SOD activity as compared to the I/R, intralipid and 1 ml/kg EIso groups. Renal morphological damages were alleviated after pretreatment of 2 or 4 ml/kg EIso. CONCLUSIONS: Intravenous EIso produces preconditioning against renal I/R injury in rats, which might be mediated by attenuating inflammation and increasing antioxidation ability.