Adaptive layer-based computer-generated holograms.

We propose a novel, to the best of our knowledge, and fast adaptive layer-based (ALB) method for generating a computer-generated hologram (CGH) with accurate depth information. A complex three-dimensional (3D) object is adaptively divided into layers along the depth direction according to its own non-uniformly distributed depth coordinates, which reduces the depth error caused by the conventional layer-based method. Each adaptive layer generates a single-layer hologram using the angular spectrum method for diffraction, and the final hologram of a complex three-dimensional object is obtained by superimposing all the adaptive layer holograms. A hologram derived with the proposed method is referred to as an adaptive layer-based hologram (ALBH). Our demonstration shows that the desired reconstruction can be achieved with 52 adaptive layers in 8.7 s, whereas the conventional method requires 397 layers in 74.9 s.

Comparison of adaptive optical scanning holography based on new evaluation methods.

Adaptive Optical Scanning Holography (AOSH) represents a powerful technique that employs an adaptive approach to selectively omit certain lines within holograms, guided by the utilization of Normalized-Mean-Error (NME) as a predictive measure. This approach effectively diminishes scanning time and conserves the storage space required for data preservation. However, there exists alternative methods superior to NME in terms of evaluating the model's efficacy. This paper introduces two novel methods, namely Normalized-Root-Mean-Square-Error (NRMSE) and Normalized-Mean-Square-Error (NMSE), into the AOSH system, leading to the development of NRMSE-AOSH and NMSE-AOSH. These new systems aim to further minimize duration of holographic recording. Through a comparative analysis of hologram lines between the two newly proposed AOSH systems and the original AOSH, we demonstrate that both NRMSE-AOSH and NMSE-AOSH effectively reduce the number of hologram lines while maintaining the hologram's informational content. Among the three methods, our two new methods exhibit better performance compared with the original method.

Circular RNA hsa_circ_0051246 acts as a microRNA-375 sponge to promote the progression of gastric cancer stem cells via YAP1.

Background: Gastric cancer (GC) stem cells play an important role in GC progression. Circular RNAs (circRNAs) act as microRNA (miRNA) sponges and inhibit the biological function of miRNAs in GC cytoplasm. MiRNAs also participate in GC progress. circ_0051246 was shown to be associated with miR-375 after analyzing GC microarray data GSE78091 and GSE83521. The oncoprotein Yes-associated protein 1 (YAP1) is targeted by miR-375 and can be inactivated via the Hippo tumor suppressor pathway. Due to insufficient research on circ_0051246, this study aimed to investigate its relationship with miR-375 and YAP1 in cancer stem cells (CSCs). Methods: SGC-7901 CSCs were used to establish knockdown/overexpression models of circ_0051246, miR-375, and YAP1. Malignant phenotypes of CSCs were assessed using Cell Counting Kit 8, colony/sphere formation, 5-Ethynyl-2'-deoxyuridine assay, flow cytometry, Transwell, and wound healing assays. To detect the interactions between circ_0051246, miR-375, and YAP1 in CSCs, a dual-luciferase reporter assay and fluorescence in situ hybridization were performed. In addition, 24 BALB/c nude mice were used to establish orthotopic xenograft tumor models. Four groups of mice were injected with CSCs (1 × 106 cells/100 µL) with circ_0051246 knockdown, miR-375 overexpression, or their respective control cells, and tumor progression and gene expression were observed by hematoxylin-eosin staining, immunohistochemistry. Western blot and quantitative real-time PCR were utilized to examine protein and gene expression, respectively. Results: Circ_0051246 silencing reduced viability, promoted apoptosis, and inhibited proliferation, migration and invasion of CSCs. The functional effects of miR-375 mimics were comparable to those of circ_0051246 knockdown; however, the opposite was observed after miR-375 inhibitors treatment of CSCs. Furthermore, circ_0051246-overexpression antagonized the miR-375 mimics' effects on CSCs. Additionally, YAP1 overexpression promoted CSC features, such as self-renewal, migration, and invasion, inhibited apoptosis and E-cadherin levels, and upregulated the expression of N-cadherin, vimentin, YAP1, neurogenic locus notch homolog protein 1, and jagged canonical notch ligand 1. Conversely, YAP1-silenced produced the opposite effect. Moreover, miR-375 treatment antagonized the malignant effects of YAP1 overexpression in CSCs. Importantly, circ_0051246 knockdown and miR-375 activation suppressed CSC tumorigenicity in vivo. Conclusion: This study highlights the promotion of circ_0051246-miR-375-YAP1 axis activation in GC progression and provides a scientific basis for research on the molecular mechanism of CSCs.

Research of the Active Components and Potential Mechanisms of Qingfei Gujin Decoction in the Treatment of Osteosarcoma Based on Network Pharmacology and Molecular Docking Technology.

Aim: Qingfei Gujin Decoction (QGD) has been shown to be effective against osteosarcoma. This research was aimed at investigating the main active ingredients and potential mechanisms of QGD acting on osteosarcoma through network pharmacology and molecular docking techniques. Methods: The active ingredients and targets of QGD were screened from the TCMSP database, and the predicted targets were obtained from the PharmMapper database. Meanwhile, the targets of osteosarcoma were collected using OMIM, PharmGKB, and DisGeNET databases. Then, GO and KEGG enrichment analyses were performed by RStudio. PPI and drug-ingredient-target networks were constructed using Cytoscape 3.2.1 to screen the major active ingredients, key networks, and targets. Finally, molecular docking of key genes and their regulatory active ingredients was performed using AutoDockTools 1.5.6 software. Results: 38 active ingredients were collected, generating 89 cross-targets; quercetin, luteolin, ß-sitosterol, and kaempferol were the main active ingredients of QGD acting on osteosarcoma, and major signaling pathways such as PI3K-Akt signaling pathway, MAPK signaling pathway, and IL-17 signaling pathway were observed. TP53, SRC, and ESR1 were identified as key proteins that docked well with their regulated compounds. Conclusion: QGD is effective against osteosarcoma through multicomponent, multitarget, and multipathway. This study was helpful for finding effective targets and compounds for osteosarcoma treatment.

miR­141 impairs mitochondrial function in cardiomyocytes subjected to hypoxia/reoxygenation by targeting Sirt1 and MFN2.

Mitochondrial oxidative stress and dysfunction are major pathogenic features of cardiac injury induced by ischemia/reperfusion (I/R). MicroRNA-141 (miR-141) has been implicated in the mitochondrial dysfunction in cell-based models of oxidant stress. Thus, the main aim of the present study was to systematically assess the role of miR-141 in cardiomyocyte injury induced by simulated I/R. The challenge of HL-1 cardiomyocytes with hypoxia/reoxygenation (H/R) decreased cell viability, which was also associated with an increase in miR-141 expression. The H/R-induced cell injury was mitigated by a miR-141 inhibitor and exacerbated by a miR-141 mimic. Furthermore, H/R induced mitochondrial superoxide production, dysfunction (decreased oxygen utilization and membrane depolarization), as well as ultrastructural damage. These mitochondrial effects were mitigated by a miR-141 inhibitor and intensified by a miR-141 mimic. Luciferase reporter assay, reverse transcription-quantitative PCR, and western blot analyses identified sirtuin-1 (Sirt1) and mitofusin-2 (MFN2) as targets of miR-141. The silencing of Sirt1 reduced the MFN2 cardiomyocyte levels and reversed the alleviating effects of miR-141 inhibitor on mitochondrial function during H/R. Collectively, these findings suggest that miR-141 functions as a causative agent in cardiomyocyte injury induced by I/R, primarily by interfering with two mitochondrial regulatory proteins, Sirt1 and MFN2.

Analysis of Clinical Manifestations and Imaging of COVID-19 Patients in Intensive Care.

Objective: The study aims to summarize and analyze the clinical and CT findings of severe COVID-19 patients. Methods: From February 11 to March 31, 2020, 61 COVID-19 patients in intensive care in the E1-3 ward of Tongji Hospital were analyzed retrospectively. Results: The main clinical manifestations were cough, expectoration in 56 cases (91.8%), shortness of breath, chest tightness in 48 cases (78.7%), fever in 61 cases (100%), muscle ache and weakness in 40 cases (65.6%), diarrhea or vomiting in 8 cases (13.1%), and headache in 4 cases (6.6%). After admission, the leukocyte count was normal in 40 cases (57.7%), higher in 9 cases (15.4%), and lower in 12 cases (26.9%). The lymphocyte count decreased in 53 cases (86.9%). CRP was increased in 29 cases (47.5%); PCT was increased in 15 cases (24.6%); ESR was increased in 38 cases (62.3%); D-dimer increased in 39 cases (63.9%); ALT/AST increased in 40 cases (65.6%); CK/CK-MB increased in 8 cases (13.1%); troponin I increased in 6 cases (9.8%); NT-proBNP increased in 35 cases (57.4%); IL-1 increased in 5 cases (8.2%); IL-2 receptor increased in 28 cases (45.9%); IL-6 increased in 23 cases (37.7%); IL-8 increased in 15 cases (24.6%); IL-10 increased in 12 cases (19.7%); and NTF increased in 22 cases (36.1%). The chest CT images showed that 38 cases (65.5%) of right lung lesions were more extensive than those of left lung lesions, 20 cases (34.5%) of left lung lesions were more extensive than those of right lung lesions, 42 cases (72.5%) of lower lobe lesions were more extensive than those of upper lobe lesions, 6 cases (10.3%) of upper lobe lesions were more extensive than those of lower lobe lesions, and 10 cases (17.2%) of upper and lower part lesions were roughly the same. Ground-glass opacity (GGO) was found in 12 cases (20.7%); GGO with focal consolidation in 38 cases (65.5%); small patchy edge fuzzy density increased in 24 cases (41.4%); large consolidation in 20 cases (34.5%); reticular or fibrous cord in 54 cases (93.1%); and air bronchogram in 8 cases (13.8%). Conclusions: COVID-19 patients in intensive care have no specific clinical manifestation and CT findings. However, analysis and summary of relevant data can help us assess the severity of the disease, decide the timing of treatment, and predict prognosis.

Off-axis optical scanning holography [Invited].

Optical scanning holography (OSH) involves the principles of optical scanning and heterodyning. The use of heterodyning leads to phase-preserving, which is the basic idea of holography. While heterodyning has numerous advantages, it requires complicated and expensive electronic processing. We investigate an off-axis approach to OSH, thereby eliminating the use of heterodyning for phase retrieval. We develop optical scanning theory for holographic imaging and show that by properly designing the scanning beam, we can perform coherent and incoherent holographic recording. Simulation results are provided to verify the proposed idea.

Comprehensive Analysis of a circRNA-miRNA-mRNA Network to Reveal Potential Inflammation-Related Targets for Gastric Adenocarcinoma.

Gastric cancer (GC) is the most common malignancy of the stomach. This study was aimed at elucidating the regulatory network of circRNA-miRNA-mRNA and identifying the precise inflammation-related targets in GC. The expression profiles of GSE83521, GSE78091, and GSE33651 were obtained from the GEO database. Interactions between miRNAs and circRNAs were investigated by the Circular RNA Interactome, and targets of miRNAs were predicted with miRTarBase. Then, a circRNA/miRNA/mRNA regulatory network was constructed. Also, functional enrichment analysis of selected differentially expressed genes (DEGs) was performed. The inflammation-/GC-related targets were collected in the GeneCards and GenLiP3 database, respectively. And a protein-protein interaction (PPI) network of DE mRNAs was constructed with STRING and Cytoscape to identify hub genes. The genetic alterations, neighboring gene networks, expression levels, and the poor prognosis of hub genes were investigated in cBioPortal, Oncomine, and Human Protein Atlas databases and Kaplan-Meier plotter, respectively. A total of 10 DE miRNAs and 33 DEGs were identified. The regulatory network contained 26 circRNAs, 10 miRNAs, and 1459 mRNAs. Functional enrichment analysis revealed that the selected 33 DEGs were involved in negative regulation of fat cell differentiation, response to wounding, extracellular matrix- (ECM-) receptor interaction, and regulation of cell growth pathways. THBS1, FN1, CALM1, COL4A1, CTGF, and IGFBP5 were selected as inflammation-related hub genes of GC in the PPI network. The genetic alterations in these hub genes were related to amplification and missense mutations. Furthermore, the genes RYR2, ERBB2, PI3KCA, and HELZ2 were connected to hub genes in this study. The hub gene levels in clinical specimens were markedly upregulated in GC tissues and correlated with poor overall survival (OS). Our results suggest that THBS1, FN1, CALM1, COL4A1, CTGF, and IGFBP5 were associated with the pathogenesis of gastric carcinogenesis and may serve as biomarkers and inflammation-related targets for GC.

Associations between interleukin gene polymorphisms and the risk of gastric cancer: A meta-analysis.

Recently, the roles of interleukin-2 (IL-2), IL-4, IL-6 and IL-8 gene polymorphisms in gastric cancer (GC) have been studied extensively, with conflicting results. Therefore, we conducted the present meta-analyses to better elucidate the roles of interleukin gene polymorphisms in GC. Eligible articles were searched in PubMed, MEDLINE, Embase, Web of Science and CNKI. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to detect any potential association between interleukin gene polymorphisms and the risk of GC. A total of 63 case-control studies was finally included in our analyses. Significant associations with the risk of GC were detected for the IL-6 rs1800796 and IL-8 rs4073 polymorphisms in overall analyses. Further subgroup analyses based on ethnicities of participants revealed that the IL-4 rs2243250, IL-6 rs1800796 and IL-8 rs4073 polymorphisms were significantly associated with the risk of GC in Asians. Moreover, IL-8 rs4073 polymorphism was also significantly associated with the risk of GC in Africans. In conclusion, our findings suggested that IL-4 rs2243250, IL-6 rs1800796 and IL-8 rs4073 polymorphisms may serve as genetic biomarkers of GC.

Interleukin-33 attenuates doxorubicin-induced cardiomyocyte apoptosis through suppression of ASK1/JNK signaling pathway.

Interleukin-33 (IL-33), a new member of the IL-1 cytokine family, has cardiac protective effect in many circumstances. The aims of present study are to assess whether IL-33 can protect cardiomyocytes from doxorubicin (DOX)-induced apoptosis and the mechanism involved in the protection. Cardiomyocytes derived from either wild-type or c-Jun N-terminal kinase deficient (JNK-/-) mice were challenged with DOX (1  µM) with or without IL-33 (10 ng/ml). Myocyte apoptosis was assessed by measuring Caspase 3 activity, fragmented DNA and the TUNEL staining. In addition, cardiomyocyte reactive oxygen species (ROS) was assessed by measuring 2',7'-dichlorofluorescin diacetate (DCFDA); apoptosis signal-regulating kinase 1(ASK1) and JNK phosphorylation were assessed with western blot analysis. Treatment of cardiomyocyes with DOX resulted in ROS generation, ASK1 and JNK phosphorylation and myocyte apoptosis. IL-33 inhibited the DOX-induced ROS, prevented ASK1 and JNK phosphorylation and attenuated the DOX-induced myocyte apoptosis. Genetic inhibition of ASK1 (ASK1 siRNA transfection) and JNK (JNK-/-) ameliorated the cardiac-protective effect of IL-33. Moreover, inhibition of ASK1 prevented the DOX-induced phosphorylation of JNK, while inhibition of JNK showed no effect on DOX-induced ASK1 phosphorylation. Our study indicates that: 1) ASK1/JNK signaling pathway is involved in DOX-induced cardiomyocyte apoptosis; 2) IL-33 protects cardiomyocytes from DOX-induced myocyte apoptosis through inhibition of the ASK1/JNK signaling pathway. IL-33 may have therapeutic potential for DOX-induced cardiac injury.

Galectin-3 Predicts Left Ventricular Remodeling of Hypertension.

Previous studies have suggested that galectin-3 is an important mediator of cardiac fibrosis. The aim of this study was to investigate the utility of galectin-3 in identifying early left ventricular remodeling (LVRM) in patients with hypertension. A total of 107 patients with hypertension and 108 controls were enrolled in this study. The levels of galectin-3 were significantly greater in hypertension patients with LVRM compared with those without LVRM. Multivariate regression analysis demonstrated that body mass index and galectin-3 were independent predictors of LVRM in the hypertension group. Only left ventricular mass was independently correlated with serum galectin-3 levels in patients with hypertension. The receiver operating characteristic analysis showed an area under the curve for galectin-3 of 0.698 (P<.001), with an optimal cutoff of 9.43 ng/mL. Therefore, galectin-3 is independently correlated with LVRM and can be regarded as a valuable biomarker of early cardiac remodeling of hypertension.

Role of HMGB1 in doxorubicin-induced myocardial apoptosis and its regulation pathway.

Doxorubicin (DOX) is a widely used anti-tumor agent. The clinical application of the medication is limited by its side effect which can elicit myocardial apoptosis and cardiac dysfunction. However, the underlying mechanism by which DOX causes cardiomyocyte apoptosis is not clear. The aim of present study is to investigate the role of high-mobility group box 1 (HMGB1) in DOX-induced myocardial injury, and signal pathway involved in regulation of HMGB1 expression in cardiomyocytes with DOX. We found treatment of isolated cardiomyocytes and naive mice with the DOX resulted in an increased HMGB1 expression which was associated with increased myocardial cell apoptosis. Pharmacological (A-box) or genetic blockade (TLR4 deficiency, TLR4(-/-)) of HMGB1 attenuated the DOX-induced myocardial apoptosis and cardiac dysfunction. In addition, our study showed that DOX resulted in an increment in the generation of peroxynitrite (ONOO(-)) and an elevation in phosphorylation of c-Jun N terminal kinase (JNK). Pretreatment of myocytes with FeTPPS, a peroxynitrite decomposition catalyst, prevented DOX-induced JNK phosphorylation, HMGB1 expression, myocardial apoptosis and cardiac dysfunction. Genetic (JNK(-/-)) or pharmacological (SP600125) inhibition of JNK ameliorated the DOX-induced HMGB1 expression and diminished myocardial apoptosis and cardiac dysfunction. Taken together, our results indicate that HMGB1 mediates the myocardial injury induced by DOX and ONOO(-)/JNK is a key regulatory pathway of myocardial HMGB1 expression induced by DOX.

Reduction in IL-33 expression exaggerates ischaemia/reperfusion-induced myocardial injury in mice with diabetes mellitus.

AIMS: The underlying mechanism(s) of vulnerability of the diabetic myocardium to ischaemia/reperfusion (I/R)-induced injury is not fully understood. Interleukin-33 (IL-33) has been reported showing the beneficial effect to the myocardium on I/R injury. The aims of this study were to test whether diabetes mellitus (DM) affects myocardial levels of IL-33 and to examine whether reduction in IL-33 is responsible for exaggerated I/R injury in the diabetic myocardium. METHODS AND RESULTS: DM hearts were challenged with I/R in vivo, whereas while isolated cardiomyocytes in vitro were conditioned with high glucose (HG) followed by an anoxia/reoxygenation (A/R) challenge. Myocardial levels of IL-33 were decreased in mice with DM which was associated with increased protein kinase C ßII (PKCßII) activation. Exogenous IL-33 prevented the DM-induced PKCßII activation and attenuated I/R injuries (myocardial infarction size and apoptosis). HG-conditioned myocytes incurred exaggerated apoptosis when compared with naïve myocytes after A/R which was attenuated by IL-33. HG activated PKCßII in cardiomyocytes, which was further enhanced by A/R. IL-33 prevented the PKCßII activation in myocytes with HG or HG and A/R. Inhibition of PKCßII prevented the beneficial effect of IL-33. Finally, IL-33 up-regulated diacylglycerol kinase zeta (DGK-zeta) in cardiomyocytes and reversed the down-regulation of myocardial DGK-zeta in mice with DM. CONCLUSION: Our results indicate that decreased levels of IL-33 are responsible for the increased sensitivity of the myocardium to I/R in DM. Reduction in IL-33 results in a chronic activation of PKCßII. I/R further enhances PKCßII activation in the diabetic myocardium which results in exaggeration of myocardial injury.

Endogenous HMGB1 contributes to ischemia-reperfusion-induced myocardial apoptosis by potentiating the effect of TNF-α/JNK.

High-mobility group box 1 (HMGB1) is a nuclear protein that has been implicated in the myocardial inflammation and injury induced by ischemia-reperfusion (I/R). The purpose of the present study was to assess the role of HMGB1 in myocardial apoptosis induced by I/R. In vivo, myocardial I/R induced an increase in myocardial HMGB1 expression and apoptosis. Inhibition of HMGB1 (A-box) ameliorated the I/R-induced myocardial apoptosis. In vitro, isolated cardiac myocytes were challenged with anoxia-reoxygenation (A/R; in vitro correlate to I/R). A/R-challenged myocytes also generated HMGB1 and underwent apoptosis. Inhibition of HMGB1 attenuated the A/R-induced myocyte apoptosis. Exogenous HMGB1 had no effect on myocyte apoptosis. However, inhibition of HMGB1 attenuated myocyte TNF-α production after the A/R was challenged; surprisingly, HMGB1 itself did not induce myocyte TNF-α production. Exogenous TNF-α induced a moderate proapoptotic effect on the myocytes, an effect substantially potentiated by coadministration of HMGB1. It is generally accepted that apoptosis induced by TNF-α is regulated by the balance of activation of c-Jun NH(2)-terminal kinase (JNK) and NF-κB. Indeed, in the present study, TNF-α increased the phosphorylation status of JNK and p65, a subunit of NF-κB; HMGB1 greatly potentiated TNF-α-induced JNK phosphorylation. Furthermore, inhibition of JNK (SP-600125) prevented the myocyte apoptosis induced by a TNF-α/HMGB1 cocktail. Finally, A/R increased HMGB1 production in both wild-type and toll-like receptor 4-deficient myocytes; however, deficiency in toll-like receptor 4 diminished A/R-induced myocyte apoptosis, TNF-α, and JNK activation. Our results indicate that myocyte-derived HMGB1 and TNF-α work in concert to promote I/R-induced myocardial apoptosis through JNK activation.

Lipopolysaccharide pretreatment protects against ischemia/reperfusion injury via increase of HSP70 and inhibition of NF-κB.

It has been reported that pretreatment of rats with lipopolysaccharide (LPS) increases myocardial functional recovery in ischemia/reperfusion (I/R) hearts. However, the mechanisms by which LPS induces cardioprotection against I/R injury have not been fully elucidated. In this study, we pretreated rats with LPS (1.0 mg/kg) 24 h before they were subjected to I/R injury, and then examined the roles of heat shock protein-70 (HSP70) and nucleus factor-κB (NF-κB) in LPS-induced cardioprotection. We observed that pretreatment with low-dose LPS resulted in significantly increased levels of HSP70 in the myocardium, which could dramatically inhibit NF-κB translocation and reduce degradation of inhibitory κB. Inhibition of NF-κB, in turn, attenuated release of inflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6) and reduced apoptosis of myocardium and infarct area following I/R injury. Moreover, HSP70 could ameliorate oxidative stress following I/R injury. To further investigate whether increase of HSP70 might be responsible for protection of the myocardium against I/R injury, we co-administered the HSP70 inhibitor, quercetin, with LPS before I/R injury. We found that LPS-induced cardioprotection was attenuated by co-administration with quercetin. Herein, we concluded that increased levels of HSP70 through LPS pretreatment led to inhibition of NF-κB activity in the myocardium after I/R injury. Our results indicated that LPS-induced cardioprotection was mediated partly through inhibition of NF-κB via increase of HSP70, and LPS pretreatment could provide a means of reducing myocardial I/R injury.

Lipopolysaccharide preconditioning enhances the efficacy of mesenchymal stem cells transplantation in a rat model of acute myocardial infarction.

BACKGROUND: Mesenchymal stem cells (MSCs)-based regenerative therapy is currently regarded as an alternative approach to salvage the acute myocardial infarcted hearts. However, the efficiency of MSCs transplantation is limited by lower survival rate of engrafted MSCs. In previous study, we found that 1.0 microg/ml Lipopolysaccharide (LPS) could protect MSCs against apoptosis induced by oxidative stress and meanwhile enhance the proliferation of MSCs. Therefore, in the present study, we firstly preconditioned MSCs with 1.0 microg/ml LPS, then transplanted MSCs into ischemic myocardium, and observed the survival and cardiac protective capacity of MSCs in a rat model of acute myocardial infarction. Furthermore, we tried to explore the underlying mechanisms and the role of Toll-like receptor-4 (TLR4) in the signal pathway of LPS-induced cardiac protection. METHODS AND RESULTS: Acute myocardial infarction model was developed by left anterior descending coronary artery ligation. 60 rats were divided into 4 groups randomly and given an intramyocardial injection of one of the following treatments: 30 microl PBS (control group), 3 x 10(6) wild MSCs/30 microl (wMSCs group), 3 x 10(6) LPS-preconditioned wild MSCs/30 microl (LPS-wMSCs group), or 3 x 10(6) LPS-preconditioned TLR4 gene deleted MSCs/30 microl (LPS-tMSCs group). After 3 weeks, LPS-preconditioned wild MSCs transplantation ameliorated cardiac function and reduced fibrosis of infarcted myocardium. Vascular density was markedly increased in LPS-wMSCs group compared with other three groups. Survival rate of engrafted MSCs was elevated and apoptosis of myocardium was reduced in infarcted heart. Expression of vascular endothelial growth factor (VEGF) and phospho-Akt was increased in the infarcted myocardium after transplantation of LPS-preconditioned MSCs. CONCLUSION: LPS preconditioning enhanced survival of engrafted MSCs, stimulated expression of VEGF and activated PI3K/Akt pathway. LPS preconditioning before MSCs transplantation resulted in superior therapeutic neovascularization and recovery of cardiac function. LPS preconditioning provided a novel strategy in maximizing biologic and functional properties of MSCs.

Lipopolysaccharides can protect mesenchymal stem cells (MSCs) from oxidative stress-induced apoptosis and enhance proliferation of MSCs via Toll-like receptor(TLR)-4 and PI3K/Akt.

Apoptosis of implanted mesenchymal stem cells (MSCs) limits the efficiency of MSC therapy. Recent studies showed the ligands of Toll-like receptors (TLRs) could control the function of these cells. We have investigated the effect of lipopolysaccharides (LPS), a ligand of TLR4, on the survival of MSCs and explored the roles of TLR4 and PI3K/Akt. H(2)O(2)/serum deprivation(H(2)O(2)/SD) induced apoptosis of MSCs but LPS-preconditioning (1.0microg/ml) protected MSCs from H(2)O(2)/SD-induced apoptosis and promoted their proliferation. Western blotting showed that 1.0microg/ml LPS enhanced phosphorylation of both Akt at Ser 473 and nuclear factor-kappa B (NF-kappaB) p65 at Ser 536. However, the protective effects of LPS on survival were not observed in TLR4(lps-del) MSCs. The results suggest appropriate treatments with LPS can protect MSCs from oxidative stress-induced apoptosis and improve the survival of MSCs via the TLR4 and PI3K/Akt pathway.

Treatment with yiqi bushen koufuye combined with chemotherapy for preventing postoperative metastasis of stomach cancer--a clinical observation of 28 cases.

OBJECTIVE: To study the effect of yiqi bushen koufiuye (oral liquid for invigorating qi and tonifying the kidney) combined with chemotherapy on postoperative metastasis of stomach cancer. METHODS: The 47 cases of postoperative stomach cancer with the syndrome of deficiency of both the spleen and kidney were divided randomly into the treatment group (28 cases), and the control group (19 cases). The control group was treated simply by chemotherapy; while the treatment group, was treated with Yiqi Bushen Koufuye in addition to chemotherapy. The effect was observed 12 months later on local relapse and distal metastasis, the life quality, peripheral hemogram, and immunologic function. RESULTS: The rates of postoperative relapse and metastasis of the treatment group were obviously lower than those of the control group (P < 0.05). The Karnofasky scores, peripheral hemogram and immunologic function of the treatment group were obviously improved in comparison with the control group (P < 0.01 or P < 0.05). CONCLUSION: Yiqi bushen koufuye combined with chemotherapy is effective in preventing postoperative metastasis of stomach cancer, increasing sensitivity and decreasing toxins, and improving the life quality and immunologic function of the patient.