Photosensitizer-singlet oxygen sensor conjugated silica nanoparticles for photodynamic therapy and bioimaging.

Intracellular singlet oxygen (1O2) generation and detection help optimize the outcome of photodynamic therapy (PDT). Theranostics programmed for on-demand phototriggered 1O2 release and bioimaging have great potential to transform PDT. We demonstrate an ultrasensitive fluorescence turn-on sensor-sensitizer-RGD peptide-silica nanoarchitecture and its 1O2 generation-releasing-storing-sensing properties at the single-particle level or in living cells. The sensor and sensitizer in the nanoarchitecture are an aminomethyl anthracene (AMA)-coumarin dyad and a porphyrin or CdSe/ZnS quantum dots (QDs), respectively. The AMA in the dyad quantitatively quenches the fluorescence of coumarin by intramolecular electron transfer, the porphyrin or QD moiety generates 1O2, and the RGD peptide facilitates intracellular delivery. The small size, below 200 nm, as verified by scanning electron microscopy and differential light scattering measurements, of the architecture within the 1O2 diffusion length enables fast and efficient intracellular fluorescence switching by the tandem ultraviolet (UV)-visible or visible-near-infrared (NIR) photo-triggering. While the red emission and 1O2 generation by the porphyrin are continually turned on, the blue emission of coumarin is uncaged into 230-fold intensity enhancement by on-demand photo-triggering. The 1O2 production and release by the nanoarchitecture enable spectro-temporally controlled cell imaging and apoptotic cell death; the latter is verified from cytotoxic data under dark and phototriggering conditions. Furthermore, the bioimaging potential of the TCPP-based nanoarchitecture is examined in vivo in B6 mice.

Distribution of Signal Peptides in Microvesicles from Activated Macrophage Cells.

Extracellular vesicles, such as microvesicles (LEV) and exosomes (SEV), play an important role in intercellular signaling by encapsulating functional molecules and delivering them to specific cells. Recent studies showed that signal peptides (SPs), which are derived from sequences at the N-terminal of newly synthesized proteins, exhibited biological activity in the extracellular fluid. We previously reported that SPs were secreted into the extracellular fluid via SEV; however, it remains unclear whether the release of SPs occurs via LEV. In the present study, we demonstrated that SP fragments from human placental secreted alkaline phosphatase (SEAP) were present in LEV as well as SEV released from RAW-Blue cells, which stably express an NF-κB-inducible SEAP reporter. When RAW-Blue cells were treated with LPS at 0-10,000 ng/mL, SEAP SP fragments per particle were more abundant in LEV than in SEV, with fragments in LEV and SEV reaching a maximum at 1000 and 100 ng/mL, respectively. The content of SEAP SP fragments in LEV from IFNγ-stimulated RAW-Blue cells was higher than those from TNFα-stimulated cells, whereas that in SEV from TNFα-stimulated RAW-Blue cells was higher than those from IFNγ-stimulated cells. Moreover, the content of SEAP SP fragments in LEV and SEV decreased in the presence of W13, a calmodulin inhibitor. Collectively, these results indicate that the transportation of SP fragments to extracellular vesicles was changed by cellular activation, and calmodulin was involved in their transportation to LEV and SEV.

Toward Feature-Preserving Vector Field Compression.

The objective of this work is to develop error-bounded lossy compression methods to preserve topological features in 2D and 3D vector fields. Specifically, we explore the preservation of critical points in piecewise linear and bilinear vector fields. We define the preservation of critical points as, without any false positive, false negative, or false type in the decompressed data, (1) keeping each critical point in its original cell and (2) retaining the type of each critical point (e.g., saddle and attracting node). The key to our method is to adapt a vertex-wise error bound for each grid point and to compress input data together with the error bound field using a modified lossy compressor. Our compression algorithm can be also embarrassingly parallelized for large data handling and in situ processing. We benchmark our method by comparing it with existing lossy compressors in terms of false positive/negative/type rates, compression ratio, and various vector field visualizations with several scientific applications.

Signal Sequence-Dependent Orientation of Signal Peptide Fragments to Exosomes.

Signal peptides (SPs) not only mediate targeting to the endoplasmic reticulum (ER) but also play important roles as biomarkers and substances with physiological activity in extracellular fluids including blood. SPs are thought to be degraded intracellularly, making it unclear how they are transported from the ER to the extracellular fluid. In a recent study, we showed that a C-terminal fragment of the SP of a type I membrane protein, amyloid precursor protein (APP), was secreted into the extracellular fluid via exosomes using transformed HEK293 cells expressing APP SP flanking a reporter protein. In the present study, we demonstrate that a N-terminal fragment of the SP from a type II membrane protein, human placental secreted alkaline phosphatase (SEAP), is contained in exosomes and secreted into the extracellular fluid using HEK-Blue hTLR3 cells, which express both a human toll-like receptor 3 gene and an inducible SEAP reporter gene. When HEK-Blue hTLR3 cells were stimulated with a TLR3 ligand, a N-terminal fragment of SEAP SP in exosomes was increased in parallel with SEAP secretion in a concentration-dependent manner. These results indicated that SP fragments are exosomal components. In addition, migrating SP fragments were determined by characteristics of the signal-anchor sequence of membrane proteins. Furthermore, we found that SP fragments could bind to calmodulin (CALM), which is a cytosolic protein and also a component of exosomes, suggesting its involvement in the transportation of SP fragments from the endoplasmic reticulum to exosomes.

Efficient compressed database of equilibrated configurations of ring-linear polymer blends for MD simulations.

To effectively archive configuration data during molecular dynamics (MD) simulations of polymer systems, we present an efficient compression method with good numerical accuracy that preserves the topology of ring-linear polymer blends. To compress the fraction of floating-point data, we used the Jointed Hierarchical Precision Compression Number - Data Format (JHPCN-DF) method to apply zero padding for the tailing fraction bits, which did not affect the numerical accuracy, then compressed the data with Huffman coding. We also provided a dataset of well-equilibrated configurations of MD simulations for ring-linear polymer blends with various lengths of linear and ring polymers, including ring complexes composed of multiple rings such as polycatenane. We executed 109 MD steps to obtain 150 equilibrated configurations. The combination of JHPCN-DF and SZ compression achieved the best compression ratio for all cases. Therefore, the proposed method enables efficient archiving of MD trajectories. Moreover, the publicly available dataset of ring-linear polymer blends can be employed for studies of mathematical methods, including topology analysis and data compression, as well as MD simulations.

Calmodulin as a Key Regulator of Exosomal Signal Peptides.

Signal peptides (SPs) and their fragments play important roles as biomarkers and substances with physiological functions in extracellular fluid. We previously reported that SP fragments were released into extracellular fluid via exosomes and bound to calmodulin (CaM), an exosomal component, in a cell-free system. However, it currently remains unclear whether CaM intracellularly interacts with SP fragments or is involved in the trafficking of these fragments to exosomes. Therefore, the present study examined the binding of CaM to SP fragments in T-REx AspALP cells, transformed HEK293 cells expressing amyloid precursor protein (APP) SP flanking a reporter protein, and their exosomes. APP SP fragments were detected in exosomes from T-REx AspALP cells in the absence of W13, a CaM inhibitor, but were present in lower amounts in exosomes from W13-treated cells. Cargo proteins, such as Alix, CD63, and CD81, were increased in W13-treated T-REx AspALP cells but were decreased in their exosomes. Furthermore, CaM interacted with heat shock protein 70 and CD81 in T-REx AspALP cells and this increased in the presence of W13. APP SP fragments were detected in intracellular CaM complexes in the absence of W13, but not in its presence. These results indicate that CaM functions as a key regulator of the transport of SP fragments into exosomes and plays novel roles in the sorting of contents during exosomal biogenesis.

Secretion of signal peptides via extracellular vesicles.

Signal peptides (SPs) consist of short peptide sequences present at the N-terminal of newly synthesizing proteins and act as a zip code for the translocation of the proteins to the endoplasmic reticulum (ER). It was thought that the SPs are intracellularly degraded after translocation to the ER; however, recent studies showed cleaved SPs have diverse roles for controlling cell functions in auto- and/or intercellular manners. In addition, it still remains obscure how SP fragments translocate away from the site where they are produced. Extracellular vesicles (EV) are important for intercellular communication and can transport functional molecules to specific cells. In this study, we show that SPs are involved in EV from T-REx AspALP cells that were transfected with a human APP SP-inducible expression vector. There was no difference in the average particle size or particle concentration of EV collected from T-REx AspALP cells and T-REx Mock cells. When the SP content in the EV was examined by mass spectrometry, the C-terminal fragment of APP SP was identified in the exosomes (SEV) of T-REx AspALP cells. In our preparation of SEV fractions, no ER-specific proteins were detected; therefore, SPs may be included in SEV but not in the debris of degraded ER. This is the first indication that SPs are secreted from cells via EV.

The sodium-glucose cotransporter-2 inhibitor Tofogliflozin prevents the progression of nonalcoholic steatohepatitis-associated liver tumors in a novel murine model.

BACKGROUND: Diabetes and obesity contribute to the pathogenesis of nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). However, how diabetes and obesity accelerate liver tumorigenesis remains to be fully understood. Moreover, to verify the therapeutic potential of anti-diabetic drugs, there exists a strong need for appropriate animal models that recapitulate human pathophysiology of NASH and HCC. METHODS: We established a novel murine model of NASH-associated liver tumors using genetically obese melanocortin 4 receptor-deficient mice fed on Western diet in combination with a chemical procarcinogen, and verified the validity of our model in evaluating drug efficacy. FINDINGS: Our model developed multiple liver tumors together with obesity, diabetes, and NASH within a relatively short period (approximately 3 months). In this model, sodium glucose cotransporter 2 inhibitor Tofogliflozin prevented the development of NASH-like liver phenotypes and the progression of liver tumors. Tofogliflozin attenuated p21 expression of hepatocytes in non-tumorous lesions in the liver. INTERPRETATION: Tofogliflozin treatment attenuates cellular senescence of hepatocytes under obese and diabetic conditions. This study provides a unique animal model of NASH-associated liver tumors, which is applicable for assessing drug efficacy to prevent or treat NASH-associated HCC.

A case of pleuroperitoneal communication in which establishing a laparoscopic pneumoperitoneum was useful for the detection of a fistula.

BACKGROUND: Pleuroperitoneal communication (PPC) is rarely observed, accounting for 1.6% of all patients who undergo continuous ambulatory peritoneal dialysis (CAPD). Although there have been several reports concerning the management of this condition, we have encountered several cases in which control failed. We herein report a valuable case of PPC in which laparoscopic pneumoperitoneum with video-assisted thoracic surgery (VATS) was useful for supporting the diagnosis and treatment. CASE PRESENTATION: The patient was a 58-year-old woman with chronic renal failure due to chronic renal inflammation who was referred to a nephrologist in our hospital to undergo an operation for the induction of CAPD. Post-operatively, she had respiratory failure, and chest X-ray and computed tomography (CT) showed right-sided hydrothorax that decreased when the injection of peritoneal dialysate was interrupted. Therefore, PPC was suspected, and she was referred to our department for surgical repair. We planned surgical treatment via video-assisted thoracic surgery. During the surgery, we failed to detect any lesions with thoracoscopy alone; we therefore added a laparoscopic port at her right-sided abdomen near the navel and infused CO2 gas into the abdominal cavity. On thoracoscopy, bubbles were observed emanating from a small pore at the central tendon of the diaphragm, which was considered to be the lesion responsible for the PPC. We closed it by suturing directly. CONCLUSIONS: VATS with laparoscopic pneumoperitoneum should be considered as an effective method for inspecting tiny pores of the diaphragm, especially when the lesions responsible for PPC are difficult to detect.

Voxel-based simulation of flow and temperature in the human nasal cavity.

The nasal airway is an extremely complex structure, therefore grid generation for numerical prediction of airflow in the nasal cavity is time-consuming. This paper describes the development of a voxel-based model with a Cartesian structured grid, which is characterized by robust and automatic grid generation, and the simulation of the airflow and air-conditioning in an individual human nasal airway. Computed tomography images of a healthy adult nose were used to reconstruct a virtual three-dimensional model of the nasal airway. Simulations of quiet restful inspiratory flow were then performed using a Neumann boundary condition for the energy equation to adequately resolve the flow and heat transfer. General agreements of airflow patterns, which were a high-speed jet posterior to the nasal valve and recirculating flow that occupied the anterior part of the upper cavity, and temperature distributions of the airflow and septum wall were confirmed by comparing in-vivo measurements with numerical simulation results.

Unusual giant multilocular mesothelial cyst of mediastinum.

BACKGROUND: Intrathoracic mesothelial cysts are congenital lesions induced by the abnormal development of the pericardial coelom. There have been a few reports of giant mesothelial cyst of the superior mediastinum, but the preferred treatment remains a controversial topic. We herein report a rare case of successful removal of giant mesothelial cyst that was incidentally detected during a medical checkup. CASE PRESENTATION: A 53-year-old man with a feeling of mild chest tightness was referred to our hospital for the evaluation of an abnormal shadow of the mediastinum on chest X-ray. Computed tomography showed a multilocular, homogenous, large cyst in the superior mediastinum measuring 18 cm in size without contrast enhancement and with spotty calcification, and magnetic resonance imaging showed a low intensity on T1-weighted images and high intensity on T2-weighted images. Therefore, a cystic thymoma, thymic cyst, lymphangioma, cystic teratoma or pericardial cyst was suspected as the preoperative diagnosis. Despite mild symptoms, the patient underwent total thymectomy under median sternotomy for an appropriate diagnosis and treatment. The pathological diagnosis was giant multilocular mesothelial cyst. CONCLUSIONS: Intrathoracic mesothelial cyst is a benign cyst and generally asymptomatic, but can sometimes induce critical chest clinical symptoms if untreated, depending on its size. In our case, complete surgical resection and a detailed pathological evaluation was effective for making the appropriate diagnosis and delivering treatment. In addition, an immunohistological evaluation is effective for diagnosing mesothelial cysts when it is difficult to distinguish the cyst from other cystic lesions.

Multifocal cholesterol granulomas of the anterior mediastinum.

BACKGROUND: Cholesterol granuloma in the mediastinum is rarely observed, accounting for 1% of all mediastinum tumors. There have been only a few reports of multifocal cholesterol granulomas of the thymus. We herein report a rare case of multifocal cholesterol granuloma in the thymus that was incidentally detected during follow-up of an aortic aneurysm. CASE PRESENTATION: The patient was a 70-year-old man with dyslipidemia and hypertension who was referred to our hospital to undergo an operation for chest aortic aneurysm. Preoperative computed tomography (CT) showed 4 lesions in the anterior mediastinum measuring up to 4 cm in size with slight contrast enhancement and spotty calcification. Therefore, a thymoma, bronchogenic cyst, or lymphangioma were considered as the preoperative diagnosis. The patient underwent total thymectomy under thoracotomy followed by aortic arch replacement for the aortic aneurysm. The pathological diagnosis was multifocal cholesterol granulomas in the thymus. CONCLUSIONS: Cholesterol granulomas should be included in the differential diagnosis of cystic tumor in the mediastinum, especially in patients with basal disease such as dyslipidemia and hypertension, which may lead to aortic aneurysm. Furthermore, complete surgical resection and a detailed histological evaluation are important for the accurate diagnosis and treatment.

Chemical sequential extraction of O horizon samples from Fukushima forests: Assessment for degradability and radiocesium retention capacity of organic matters.

To investigate how radiocesium (137Cs) is retained in the O horizon via interactions with organic matter, we collected O horizon samples in Japanese cedar (Cryptomeria japonica) and konara oak (Quercus serrata) forest sites in Fukushima during the 8 years following the Fukushima Dai-ichi Nuclear Power Plant accident. To assess degradability and 137Cs retention capacity of organic matter, we conducted chemical sequential extraction with organic solvent and sulfuric acid, collecting the following fractions: organic solvent extractives (Fraction 1), acid-soluble carbohydrates (Fraction 3), and acid-insoluble residue (Fraction 4). In all samples, across sampling years and sites, 137Cs content in Fractions 1, 3, and 4, as a proportion of the total 137Cs content, was 0.0-23.6%, 18.4-42.9%, and 44.8-76.0%, respectively. Generally, 137Cs is considered to be electrostatically bound to organic matter and relatively mobile, making it easily extractable by sulfuric acid treatment. However, we observed a relatively high proportion of 137Cs in Fraction 4, suggesting strong retention of 137Cs and their immobility in the O horizon. Complex organic matter such as lignin or tannin may contribute this retention. We also noted that some part of 137Cs may be also retained by clay minerals in the O horizon. Although organic matter in Fractions 1 and 3 is considered to decompose faster than that in Fraction 4, over the observation period the 137Cs proportion and net rate of decrease in 137Cs content (in total and in each fraction) remained nearly constant. This result implies that decomposition of organic matter and the consequent release of bound 137Cs may be partly compensated by additional input of 137Cs from the canopy and 137Cs recycling by soil microorganisms. Our study highlights the potential role of organic matter in the O horizon as a temporary reservoir of 137Cs and a driver of the 137Cs cycle in forest ecosystems.

Superior vena cava replacement combined with venovenous shunt for thymic carcinoma.

INTRODUCTION: Advanced-stage thymic malignancies are a heterogeneous group of mediastinal tumors that include thymoma and thymic carcinoma infiltrating the surrounding thoracic structures. When the tumor infiltrates the superior vena cava (SVC), radical resection can be selectively achieved via en bloc SVC resection and its prosthetic conduit replacement. We herein report a case of SVC replacement for thymic carcinoma en bloc radical resection. CASE PRESENTATION: A 75-year-old Japanese man presented at our hospital due to progressive dyspnea and edema of his face and upper extremities. CT showed a 55 × 40 × 38-mm tumor located at the anterior mediastinum lesion. This tumor had invaded the superior vena cava and both brachiocephalic veins. We performed surgical resection for the thymic carcinoma located at the mediastinum that invaded the superior vena cava and both brachiocephalic veins. The surgery was performed through a full median sternotomy and transmanubrial approach without using an artificial heart and lung. The tumor involved the SVC, right brachiocephalic vein (RBCV) and left brachiocephalic vein (LBCV). We performed SVC replacement for thymic carcinoma en bloc radical resection. DISCUSSION: This report has two important implications. First, a venovenous shunt (VVS) from the distal LBCV to the right auricle was very useful and safe before performing an SVC complete clamp. The second implication of our study was that using a PTFE with a large inner diameter may prevent thrombus occlusion. CONCLUSIONS: We experienced SVC replacement for thymic carcinoma en bloc radical resection. We were able to safely performed this surgery using our usual approach.

A minimally invasive and safe surgical approach to resect anterior superior sulcus tumors.

INTRODUCTION: Superior sulcus tumors (SSTs) are a wide range of tumors invading a section of the apical chest wall called the thoracic inlet. The unique characteristics of SSTs lie in the anatomy of the region where these tumors occur. For this reason, a surgical approach to treating these tumors is technically demanding, and complete resection may be difficult to accomplish. CASE PRESENTATION: A 71-year-old Japanese man presented at our hospital due to left anterior chest pain and an abnormal chest CT scan showing a 40 × 33 × 30-mm tumor located in the left anterior apex of the thoracic inlet. This tumor had invaded the first and second rib and was located near the subclavian vein. There was no significant distant metastasis. Therefore, we performed surgical resection. The surgical procedure included three steps. First, we performed VATS observation via the left thoracic cavity. Second, via the transmanubrial approach, we obtained tumor-free margins of the anterior cervical structures. Third, through VATS in the left lateral decubitus position, we performed left upper lobectomy and mediastinal lymph node dissection. This surgery was successful, with no postoperative complications. DISUCUSSION: This surgical approach was effective and safe for treating a superior sulcus tumor located the anterior apex of the thoracic inlet. Next, VATS lobectomy is minimally invasive and safe after the transmanubrial approach for managing anterior superior sulcus tumor. CONCLUSION: We experienced a case of locally advanced superior sulcus tumor located at the anterior apex of the thoracic inlet and performed complete resection.

Novel Oxindole-Curcumin Hybrid Compound for Antioxidative Stress and Neuroprotection.

Oxidative stress plays an important role in the pathogenesis of Parkinson's disease and other neurodegenerative disorders. The oxindole compound GIF-2165X-G1 is a hybrid molecule composed of the oxindole skeleton of the neuroprotective compound GIF-0726-r and the polyphenolic skeleton of the antioxidant curcumin. We previously reported that novel oxindole derivatives such as GIF-0726-r and GIF-2165X-G1 prevent endogenous oxidative stress-induced cell death in mouse hippocampal HT22 cells. In this study, we present a detailed investigation of the effect of GIF-2165X-G1 on endogenous oxidative stress in HT22 cells in comparison with GIF-0726-r and curcumin. GIF-2165X-G1 exhibited more potent neuroprotective activity than GIF-0726-r or curcumin and had less cytotoxicity than that observed with curcumin. Both GIF-0726-r and GIF-2165X-G1 were found to have ferrous ion chelating activity similar to that exhibited by curcumin. GIF-2165 X-G1 and curcumin induced comparable antioxidant response element transcriptional activity. Although the induction of heme oxygenase-1, an antioxidant response element-regulated gene product, was much stronger in curcumin-treated cells than in GIF-2165X-G1-treated cells, it turned out that the induction of heme oxygenase-1 is dispensable for neuroprotection. These results demonstrate that the introduction of the polyphenol skeleton of curcumin to the oxindole GIF-0726-r improves neuroprotective features. Furthermore, intrastriatal injection of GIF-2165X-G1 alleviated apomorphine-induced rotation and prevented dopaminergic neuronal loss in a 6-hydroxydopamine mouse model of Parkinson's diseases. Collectively, our novel findings indicate that the novel oxindole compound GIF-2165X-G1 serves to delay the progression of Parkinson's disease by suppressing oxidative stress.

Two extremely rare cases of extrapleural hematoma.

BACKGROUND: Extrapleural hematoma is uncommon. However, according to the size of hematoma and/or the progression of anemia, surgical treatment to control bleeding might be necessary because a huge hematoma can cause ventilator and circulatory disturbances to press heart and lung. We present two unusual cases of huge extrapleural hematoma in an anticoagulated patient with no apparent history of trauma or otherwise traumatic episodes. CASE PRESENTATION: Case 1: A 78-year-old man presented to our emergency department with pain in his right shoulder and disturbance of consciousness. He had no apparent history of trauma. Computed tomography (CT) of the chest revealed the presence of a huge lens-like encapsulated lesion measuring 220 × 90 mm in the right thoracic cavity. These findings all supported a diagnosis of extrapleural hematoma with hemothorax. Case 2: A 73-year-old man was brought to our hospital by ambulance after bruising his back in his house. CT of the chest revealed the presence of a huge lens-like encapsulated lesion measuring 230 × 70 mm in the left thoracic cavity. Hemorrhagic effusion was obtained by thoracocentesis, and the lesion was suspected of being a hematoma. In both two cases, we performed video-assisted thoracic surgery (VATS), which was minimally invasive and effective. These two patients were cured and discharged smoothly after surgery. CONCLUSIONS: We reported two rare cases of extrapleural hematoma. This disease requires close attention when it manifests in patients undergoing anticoagulation therapy. Regarding treatment, VATS was particularly effective in these cases.

Voxel-based modeling of airflow in the human nasal cavity.

This paper describes the simulation of airflow in human nasal airways using voxel-based modeling characterized by robust, automatic, and objective grid generation. Computed tomography scans of a healthy adult nose are used to reconstruct 3D virtual models of the nasal airways. Voxel-based simulations of restful inspiratory flow are then performed using various mesh sizes to determine the level of granularity required to adequately resolve the airflow. For meshes with close voxel spacings, the model successfully reconstructs the nasal structure and predicts the overall pressure drop through the nasal cavity.

Frankia communities at revegetating sites in Mt. Ontake, Japan.

In 1984 at Mt. Ontake in Japan, an earthquake caused a devastating landslide, and as a result, the vegetation on the south slope of the mountain was completely eliminated. In higher elevation (2000 m) areas, revegetation has not yet been completed even 30 years after the landslide. Revegetation progress throughout the area was heterogeneous. In the partially revegetated areas, actinorhizal plant species such as Alnus maximowiczii and Alnus matsumurae have been found. In the present study, we investigated the Frankia communities in the higher-elevation area using sequence analysis of the amplified nifH (dinitrogenase reductase) gene from nodule and soil samples collected in the disturbed region, undisturbed forest, and in the boundary between the disturbed region and the undisturbed forest. Phylogenetic analysis of partial nifH sequences revealed the presence of six clusters, each of which consisted of highly similar (> 99%) sequences. Four clusters showed significant sequence similarity to Frankia (three Alnus- and a Casuarina-infecting strains). Diversity in the Frankia community was relatively low-only one or two clusters were detected in a site. At most of the sampling sites, a dominant cluster in a nodule coincided with that in rhizosphere soil, indicating that community structure in the rhizosphere is a primary factor that determines occupancy in a nodule. No significant difference in community structure was observed between plant species. Diversity in the Frankia community varied depending on revegetation progress. Cluster A, which was the most dominant in the disturbed region, was likely to have invaded from undisturbed forest.

High-density lipoprotein suppresses tumor necrosis factor alpha production by mycobacteria-infected human macrophages.

Immune responses to parasitic pathogens are affected by the host physiological condition. High-density lipoprotein (HDL) and low-density lipoprotein (LDL) are transporters of lipids between the liver and peripheral tissues, and modulate pro-inflammatory immune responses. Pathogenic mycobacteria are parasitic intracellular bacteria that can survive within macrophages for a long period. Macrophage function is thus key for host defense against mycobacteria. These basic facts suggest possible effects of HDL and LDL on mycobacterial diseases, which have not been elucidated so far. In this study, we found that HDL and not LDL enhanced mycobacterial infections in human macrophages. Nevertheless, we observed that HDL remarkably suppressed production of tumor necrosis factor alpha (TNF-α) upon mycobacterial infections. TNF-α is a critical host-protective cytokine against mycobacterial diseases. We proved that toll-like receptor (TLR)-2 is responsible for TNF-α production by human macrophages infected with mycobacteria. Subsequent analysis showed that HDL downregulates TLR2 expression and suppresses its intracellular signaling pathways. This report demonstrates for the first time the substantial action of HDL in mycobacterial infections to human macrophages.