Primary Splenic Lymphoma Associated with Hemophagocytic Lymphohistiocytosis Complicated with Splenic Rupture

Primary splenic lymphoma (PSL) is a rare disease with ambiguous definition, comprising less than 1% of non-Hodgkin's lymphoma. Even rarer is PSL combined with hemophagocytic lymphohistiocytosis (HLH), which has presentations of fever, cytopenia, hepatosplenomegaly, hyperferritinemia, and phagocytosis of hematopoietic cells in the reticuloendothe-lial system. We report the case of a 77-year-old man who presented with HLH initially. Refusing diagnostic splenectomy, he received chemotherapy. Spontaneous splenic rupture occurred after chemotherapy. In the following emergency operation, PSL was diagnosed. He received another 5 courses of chemotherapy with the R-CNOP regimen (rituximab, cyclophosphamide, mitoxantrone, vincristine, prednisolone). Now he has no residual or relapsed disease. Diagnostic splenectomy for adult HLH patients without definite etiologies may play an important role. [J Chin Med Assoc 2008;71(4):210–213

Ocimum gratissimum Aqueous Extract Induces Apoptotic Signalling in Lung Adenocarcinoma Cell A549

Ocimum gratissimum (OG) is widely used as a traditional herb for its antibacterial activity in Taiwan. Recently, antitumor effect of OG on breast cancer cell is also reported; however, the effects of OG on human pulmonary adenocarcinoma cell A549 remain unclear. Therefore, we aimed to investigate whether aqueous OG extract (OGE) affects viability of A549 cells and the signals induced by OGE in A549 cells. Cell viability assays revealed that OGE significantly and dose-dependently decreased the viability of A549 cell but not that of BEAS-2B cell. Morphological examination and DAPI staining indicated that OGE induced cell shrinkage and DNA condensation for A549 cells. Further investigation showed that OGE enhanced activation of caspase-3, caspase-9 and caspase-8 and increased protein level of Apaf-1 and Bak, but diminished the level of Bcl-2. Additionally, OGE inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) yet enhanced the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAP kinase (p38). In conclusion, our findings indicate that OGE suppressed the cell viability of A549 cells, which may result from the activation of apoptotic signaling and the inhibition of anti-apoptotic signaling, suggesting that OGE might be beneficial to lung carcinoma treatment

Ocimum gratissimum Aqueous Extract Protects H9c2 Myocardiac Cells from H2O2-Induced Cell Apoptosis through Akt Signalling

Increased cell death of cardiomyocyte by oxidative stress is known to cause dysfunction of the heart. O. gratissimum is one of the more well-known medicinal plants among the Ocimum species and widely used in treatment of inflammatory diseases. In this study, we hypothesized that aqueous extract of O. gratissimum leaf (OGE) may protect myocardiac cell H9c2 from oxidative injury by hydrogen peroxide (H2O2). Our results revealed that OGE pretreatment dose-dependently protects H9c2 cells from cell death when exposed to H2O2. Additionally, DNA condensation induced by H2O2 was also reduced by OGE pretreatment, suggesting that Ocimum gratissimum extract may attenuate H2O2-induced chromosome damage. Further investigation showed that OGE pretreatment inhibited H2O2-induced activation of caspase-3 and caspase-9, as well as H2O2-induced upregulation of proapoptotic Apaf-1 and the release of cytosolic cytochrome c, but has little effect on the activation of caspase-8. Additionally, OGE pretreatment significantly upregulated Bcl-2 expression and Akt phosphorylation, and slightly affected the phosphorylation of mitogen-activated protein kinases including p38 MAPK and JNK. Taken together, our findings revealed that Ocimum gratissimum extract effectively inhibited the mitochondrial pathway and upregulated Bcl-2 expression, which may be important in protecting H9c2 cells from H2O2-induced cell death

Chemokine receptor CX3CR1 contributes to macrophage survival in tumor metastasis

Chinese Ministry of Science and Technology [2009CB522205, 2012CB945104]; National Science Foundation of China [81170120, 31090363]; Beijing Nova Program [Z121107002512041]Background: Macrophages, the key component of the tumor microenvironment, are differentiated mononuclear phagocyte lineage cells that are characterized by specific phenotypic characteristics that have been implicated in tumor growth, angiogenesis, and invasion. CX3CR1, the chemoattractant cytokine CX3CL1 receptor, plays an important role in modulating inflammatory responses, including monocyte homeostasis and macrophage phenotype and function. However, the role of CX3CR1 in the regulation of the tumor inflammatory microenvironment is not fully understood. Methods: Using in vivo hepatic metastasis model, human colon carcinoma specimens, immunohistochemical staining, TUNEL staining, flow cytometry analysis, Western blotting assay and co-culture in three-dimensional peptide gel, we determined the effects of CX3CR1 on angiogenic macrophage survival and tumor metastasis. Results: In this study, we found that CX3CR1 was expressed in human colon carcinomas in a histologic grade-and stage-dependent manner, and CX3CR1 upregulation in TAMs was correlated with poor prognosis. Furthermore, we showed that in a microenvironment lacking CX3CR1, the liver metastasis of colon cancer cells was significantly inhibited. The underlying mechanism is associated with decrease accumulation of angiogenic macrophages that can be partly attributed to increased apoptosis in the tumor microenvironment, thus leading to impaired tumor angiogenesis in the liver and suppressed tumor metastasis. Conclusions: Our results suggest a role of CX3CR1 in angiogenic macrophage survival in the tumor microenvironment contributing to tumor metastasis

A Force Sensorless Method for CFRP/Ti Stack Interface Detection during Robotic Orbital Drilling Operations

Drilling carbon fiber reinforced plastics and titanium (CFRP/Ti) stacks is one of the most important activities in aircraft assembly. It is favorable to use different drilling parameters for each layer due to their dissimilar machining properties. However, large aircraft parts with changing profiles lead to variation of thickness along the profiles, which makes it challenging to adapt the cutting parameters for different materials being drilled. This paper proposes a force sensorless method based on cutting force observer for monitoring the thrust force and identifying the drilling material during the drilling process. The cutting force observer, which is the combination of an adaptive disturbance observer and friction force model, is used to estimate the thrust force. An in-process algorithm is developed to monitor the variation of the thrust force for detecting the stack interface between the CFRP and titanium materials. Robotic orbital drilling experiments have been conducted on CFRP/Ti stacks. The estimate error of the cutting force observer was less than 13%, and the stack interface was detected in 0.25 s (or 0.05 mm) before or after the tool transited it. The results show that the proposed method can successfully detect the CFRP/Ti stack interface for the cutting parameters adaptation

Comparison of Chemical Compositions of the Pepper EOs From Different Cultivars and Their AChE Inhibitory Activity

© The Author(s) 2020. Pepper is one of the most popular spices over the world and is called the King of Spices. Its essential oils (EOs) could alleviate neuronal ailments due to the inhibitory effect against acetylcholinesterase (AChE). In this study, the chemical compositions of 26 EOs prepared from white and black pepper collecting from 6 different cultivars were analyzed by gas chromatography-mass spectrometry (GC-MS). A total of 133 compounds were identified in the white and black pepper EOs. Monoterpenes and sesquiterpenes were found to be riched in these EOs, of which α-pinene, β-pinene, sabinene, 3-carene, limonene, and (E)-β-caryophyllene were the major constituents. Most of pepper EOs showed potential AChE inhibitory activity with half-maximal inhibitory concentration (IC50) values in the range of 0.5-182.5 µg/mL. Comparison of chemical constitutes of pepper EOs from different cultivars suggested that α-pinene, β-pinene, and 3-carene with an IC50 value of 3.2, 53.3, and 2.9 µg/mL, respectively, might be used as Quality-marker (Q-marker) of pepper oil in inhibiting AChE

Probing topcolor-assisted technicolor from top charge asymmetry and triple-top production at the LHC

In a topcolor-assisted technicolor model (TC2) with large FCNC top quark couplings, we study its correlated contributions to the top quark forward-backward asymmetry ($A_{FB}$) at the Tevatron, the top charge asymmetry ($A_{C}$) and the triple-top production at the LHC. Under current constraints on the top quark from the LHC and Tevatron(such as the total and differential production rates), we scan the parameter space of such a TC2 model. We find that in the allowed parameter space the TC2 model can explain the Tevatron measured $A_{FB}$ at $2\sigma$ level, but meanwhile significantly enhance $A_{C}$ at the LHC. Such enhanced $A_{C}$, albeit currently allowed by the LHC measurement at $2\sigma$ level, will serve as a test of TC2 with the improvement of measurement precision at the LHC. Then with all the constraints (including the requirement to explain $A_{FB}$ at $2\sigma$ level and satisfying the current LHC measurement of $A_{C}$ at $2\sigma$ level), we find that the TC2 model can induce sizable triple-top production at the 14 TeV LHC (the production rate can maximally reach 16 pb). Due to the low SM backgrounds, the triple-top production can also be a good probe for TC2 model, complementary to $A_{C}$.Comment: 15 pages, 5 figures, new constraints from LHC addded, published version(Phys. Lett. B

Multidrug-resistant Pseudomonas aeruginosa is predisposed to lasR mutation through up-regulated activity of efflux pumps in non-cystic fibrosis bronchiectasis patients

BackgroundMultidrug-resistant (MDR) Pseudomonas aeruginosa is a frequent opportunistic pathogen that causes significant mortality in patients with non-cystic fibrosis bronchiectasis (NCFB). Although the quorum sensing (QS) system is a potential target for treatment, lasR mutants that present with a QS-deficient phenotype have been frequently reported among clinical P. aeruginosa isolates. We aimed to investigate whether antibiotic resistance would select for lasR mutants during chronic P. aeruginosa lung infection and determine the mechanism underlying the phenomenon.MethodsWe prospectively evaluated episodes of chronic P. aeruginosa lung infections in NCFB patients over a 2-year period at two centers of our institution. QS phenotypic assessments and whole-genome sequencing (WGS) of P. aeruginosa isolates were performed. Evolution experiments were conducted to confirm the emergence of lasR mutants in clinical MDR P. aeruginosa cultures.ResultsWe analyzed episodes of P. aeruginosa infection among 97 NCFB patients and found only prior carbapenem exposure independently predictive of the isolation of MDR P. aeruginosa strains. Compared with non-MDR isolates, MDR isolates presented significantly QS-deficient phenotypes, which could not be complemented by the exogenous addition of 3OC12-HSL. The paired isolates showed that their QS-phenotype deficiency occurred after MDR was developed. Whole-genome sequencing analysis revealed that lasR nonsynonymous mutations were significantly more frequent in MDR isolates, and positive correlations of mutation frequencies were observed between genes of lasR and negative-efflux-pump regulators (nalC and mexZ). The addition of the efflux pump inhibitor PAβN could not only promote QS phenotypes of these MDR isolates but also delay the early emergence of lasR mutants in evolution experiments.ConclusionsOur data indicated that MDR P. aeruginosa was predisposed to lasR mutation through the upregulated activity of efflux pumps. These findings suggest that anti-QS therapy combined with efflux pump inhibitors might be a potential strategy for NCFB patients in the challenge of MDR P. aeruginosa infections