Notes

Prospective Evaluation of (99m)Tc-sestamibi SPECT/CT for that Carried out Renal Oncocytomas along with Hybrid Oncocytic/Chromophobe Cancers.
The liver is a highly regenerative organ, but its regenerative capacity is compromised in severe liver diseases. Hepatocyte-driven liver regeneration that involves the proliferation of preexisting hepatocytes is a primary regeneration mode. On the other hand, liver progenitor cell (LPC)-driven liver regeneration that involves dedifferentiation of biliary epithelial cells or hepatocytes into LPCs, LPC proliferation, and subsequent differentiation of LPCs into hepatocytes is a secondary mode. This secondary mode plays a significant role in liver regeneration when the primary mode does not effectively work, as observed in severe liver injury settings. Thus, promoting LPC-driven liver regeneration may be clinically beneficial to patients with severe liver diseases. In this review, we describe the current understanding of LPC-driven liver regeneration by exploring current knowledge on the activation, origin, and roles of LPCs during regeneration. We also describe animal models used to study LPC-driven liver regeneration, given their potential to further deepen our understanding of the regeneration process. This understanding will eventually contribute to developing strategies to promote LPC-driven liver regeneration in patients with severe liver diseases.Grincamycins (GCNs) are a class of angucycline glycosides isolated from actinomycete Streptomyces strains that have potent antitumor activities, but their antitumor mechanisms remain unknown. In this study, we tried to identify the cellular target of grincamycin B (GCN B), one of most dominant and active secondary metabolites, using a combined strategy. We showed that GCN B-selective-induced apoptosis of human acute promyelocytic leukemia (APL) cell line NB4 through increase of ER stress and intracellular reactive oxygen species (ROS) accumulation. Using a strategy of combining phenotype, transcriptomics and protein microarray approaches, we identified that isocitrate dehydrogenase 1(IDH1) was the putative target of GCN B, and confirmed that GCNs were a subset of selective inhibitors targeting both wild-type and mutant IDH1 in vitro. It is well-known that IDH1 converts isocitrate to 2-oxoglutarate (2-OG), maintaining intracellular 2-OG homeostasis. IDH1 and its mutant as the target of GCN B were validated in NB4 cells and zebrafish model. Knockdown of IDH1 in NB4 cells caused the similar phenotype as GCN B treatment, and supplementation of N-acetylcysteine partially rescued the apoptosis caused by IDH1 interference in NB4 cells. In zebrafish model, GCN B effectively restored myeloid abnormality caused by overexpression of mutant IDH1(R132C). Taken together, we demonstrate that IDH1 is one of the antitumor targets of GCNs, suggesting wild-type IDH1 may be a potential target for hematological malignancies intervention in the future.Baicalein is a natural flavonoid extracted from the root of Scutellaria baicalensis that exhibits a variety of pharmacological activities. In this study, we investigated the molecular mechanisms underlying the protective effect of baicalein against cardiac hypertrophy in vivo and in vitro. Cardiac hypertrophy was induced in mice by injection of isoproterenol (ISO, 30 mg·kg-1·d-1) for 15 days. The mice received caudal vein injection of baicalein (25 mg/kg) on 3rd, 6th, 9th, 12th, and 15th days. We showed that baicalein administration significantly attenuated ISO-induced cardiac hypertrophy and restored cardiac function. The protective effect of baicalein against cardiac hypertrophy was also observed in neonatal rat cardiomyocytes treated with ISO (10 μM). In cardiomyocytes, ISO treatment markedly increased reactive oxygen species (ROS) and inhibited autophagy, which were greatly alleviated by pretreatment with baicalein (30 μM). We found that baicalein pretreatment increased the expression of catalase and the mitophagy receptor FUN14 domain containing 1 (FUNDC1) to clear ROS and promote autophagy, thus attenuated ISO-induced cardiac hypertrophy. Furthermore, we revealed that baicalein bound to the transcription factor FOXO3a directly, promoting its transcription activity, and transactivated catalase and FUNDC1. In summary, our data provide new evidence for baicalein and FOXO3a in the regulation of ISO-induced cardiac hypertrophy. Baicalein has great potential for the treatment of cardiac hypertrophy.Two new dimeric cyclohexapeptides, chloptosins B and C, were discovered from the culture broth of Embleya sp. MM621-AF10 together with the known compounds chloptosin and L-156,602. The structures of the new chloptosins were determined by spectroscopic studies and advanced Marfey's methods. The stereo structure of the constituent isoleucine was determined by C3 Marfey's analysis. Chloptosins demonstrated potent antimicrobial activity against Gram-positive bacteria including drug-resistant strains of methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci with MICs of 0.5-2 µg ml-1. The antimicrobial activities of chloptosins were enhanced by addition of co-producing compound L-156,602, as shown by checkerboard analysis.Sustained B-cell activation is an important mechanism contributing to B-cell lymphoma (BCL). We aimed to validate four previously reported B-cell activation markers predictive of BCL risk (sCD23, sCD27, sCD30, and CXCL13) and to examine their possible mediating effects on the association between anthropometric and lifestyle factors and major BCL subtypes. Pre-diagnostic serum levels were measured for 517 BCL cases and 525 controls in a nested case-control study. The odds ratios of BCL were 6.2 in the highest versus lowest quartile for sCD23, 2.6 for sCD30, 4.2 for sCD27, and 2.6 for CXCL13. Higher levels of all markers were associated with increased risk of chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). Following mutual adjustment for the other immune markers, sCD23 remained associated with all subtypes and CXCL13 with FL and DLBCL. The associations of sCD23 with CLL and DLBCL and CXCL13 with DLBCL persisted among cases sampled > 9 years before diagnosis. sCD23 showed a good predictive ability (area under the curve = 0.80) for CLL, in particular among older, male participants. sCD23 and CXCL13 showed a mediating effect between body mass index (positive) and DLBCL risk, while CXCL13 contributed to the association between physical activity (inverse) and DLBCL. Our data suggest a role of B-cell activation in BCL development and a mediating role of the immune system for lifestyle factors.Triplet-drug regimen bortezomib-thalidomide-dexamethasone (VTD) and bortezomib-lenalidomide-dexamethasone (VRD) are considered as standard of care induction prior autologous stem-cell transplantation (ASCT) in myeloma. In addition to improve response rate, induction therapy should preserve an adequate stem-cell collection. In the present retrospective study, we analyzed stem-cell collection in 325 newly diagnosed myeloma patients who received either VTD or VRD induction before ASCT. Stem-cell mobilization consisted of intravenous cyclophosphamide plus G-CSF. Plerixafor was administered preemptively to rescue mobilization. Remdesivir In comparison with VTD, VRD induction was associated with a more frequent use of plerixafor (19.3% versus 5.4%, p = 0.004) and with an increased number of apheresis to reach adequate collection (>2 apheresis required in 42.3% versus 30.2%, p = 0.05). Moreover, more patients experienced collection failure in the VRD group (6% versus 1.8%, p = 0.004). The median number of CD34-positive cells (×106/kg) was lower in the VRD group 8.5 versus 9.3 (p = 0.05) in the VTD group. The vast majority of patients underwent ASCT (93% versus 98%, in VRD and VTD group, respectively). These data highlight the need of optimal stem-cell collection strategy, especially in the context of tandem transplantation and incorporation of anti-CD38 monoclonal antibody into induction.The aim of this study was to develop a comprehensive system for predicting non-relapse mortality after allogeneic hematopoietic cell transplantation (HCT) during first complete remission (CR) of acute myeloid leukemia (AML). After dividing 2344 eligible patients randomly into a training set and a validation set, we first identified and scored five parameters, that is, age, sex, performance status, HCT-comorbidity index (HCT-CI), and donor type, on the basis of their impact on non-relapse mortality for patients in the training set. The non-relapse mortality-J (NRM-J) index using the sum of these scores was then applied to patients in the validation set, resulting in a clear differentiation of non-relapse mortality, with expected 2-year rates of 11%, 16%, 27%, and 33%, respectively (P  less then  0.001). The estimated c-statistic was 0.67, which was significantly higher than that of the European Society for Blood and Marrow Transplantation score (0.60, P = 0.002) and the HCT-CI (0.57, P  less then  0.001). The NRM-J index showed a significant association with overall survival, but not with relapse. Our findings demonstrate that the NRM-J index is useful for predicting post-transplant non-relapse mortality for patients with AML in first CR, for whom the decision of whether to perform allogeneic HCT is critical.Growing evidence demonstrates circadian rhythms of pain hypersensitivity in various chronic disorders. In chemotherapy-induced peripheral neuropathy (CIPN), agents such as paclitaxel are known to elicit chronic neuropathic pain in cancer patients and seriously compromise their quality of life. Here, we report that the mechanical threshold for allodynia in paclitaxel-treated rats exhibited a robust circadian oscillation, reaching the nadir during the daytime (inactive phase). Using Per2LucSV circadian reporter mice expressing a PER2LUC fusion protein, we isolated dorsal root ganglia (DRG), the primary sensory cell body for peripheral nerve injury generated hypersensitivity, and monitored ex vivo reporter bioluminescence. We observed strong circadian reporter rhythms in DRG neurons which are highly entrainable by external cues. Paclitaxel treatment significantly lengthened DRG circadian periods, with little effects on the amplitude of oscillation. We further observed the core protein BMAL1 and PER2 in DRG neurons and satellite cells. Using DRG and dorsal horn (DH; another key structure for CIPN pain response) tissues from vehicle and paclitaxel treated rats, we performed RNA-sequencing and identified diurnal expression of core clock genes as well as clock-controlled genes in both sites. Interestingly, 20.1% and 30.4% of diurnal differentially expressed genes (DEGs) overlapped with paclitaxel-induced DEGs in the DRG and the DH respectively. In contrast, paclitaxel-induced DEGs displayed only a modest overlap between daytime and nighttime (Zeitgeber Time 8 and 20). Furthermore, paclitaxel treatment induced de novo diurnal DEGs, suggesting reciprocal interaction of circadian rhythms and chemotherapy. Our study therefore demonstrates a circadian oscillation of CIPN and its underlying transcriptomic landscape.The transport of particles and fluids through multichannel microfluidic networks is influenced by details of the channels. Because channels have micro-scale textures and macro-scale geometries, this transport can differ from the case of ideally smooth channels. Surfaces of real channels have irregular boundary conditions to which streamlines adapt and with which particle interact. In low-Reynolds number flows, particles may experience inertial forces that result in trans-streamline movement and the reorganization of particle distributions. Such transport is intrinsically 3D and an accurate measurement must capture movement in all directions. To measure the effects of non-ideal surface textures on particle transport through complex networks, we developed an extended field-of-view 3D macroscope for high-resolution tracking across large volumes ([Formula see text]) and investigated a model multichannel microfluidic network. A topographical profile of the microfluidic surfaces provided lattice Boltzmann simulations with a detailed feature map to precisely reconstruct the experimental environment.
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