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关键词： Asperuloside   Lipopolysaccharide   Chronic periodontitis   TLR 4   NF-KB  

摘要： Objective: The mechanism underlying lipopolysaccharide (LPS)-induced primary human periodontal ligament (PDLC) cell injury is unclear. In this study, we focused on the therapeutic function of asperuloside (ASP) on LPSinduced cell injury. Design: The study enrolled 41 participants, including 18 healthy controls and 23 CP patients. Western blotting was used to measure the expression of Toll-like receptor 4 (TLR4), phosphorylated p65 (p-p65) and cyclin D1. Enzyme-linked immunosorbent assays (ELISAs) were utilized to evaluate the protein levels of proinflammatory factors interleukin (IL)-113, IL-6, IL-8 and tumor necrosis factor alpha (TNF-a). MTT assays and 5-ethynyl-2 ' deoxyuridine (EdU) staining were performed to investigate cell proliferation. Immunohistochemistry was used to detect TLR4 and p65 expression in gingival tissues. Results and conclusions: Asperuloside ameliorates lipopolysaccharide-induced PDLC cell injury by decreasing TLR4 expression and NF-KB activation, while this protective effect of ASP was reversed by TLR4 overexpression.

关键词： Cancer   Metastasis   Metastatic potential   Liver cancer   Primary tumor   Cancer cell lines  

摘要： Although metastases from original (primary) tumors are highly studied, metastases from metastatic sites (secondary tumors) are far less studied. Here, using data from metastasis map (MetMap) project reported in a recent study (Jin et al. in Nature 588(7837): 331-336. , 2020), we found that human cancer cell lines isolated from metastatic sites have higher potential to metastasize to another site in mice, compared to human cancer cell lines isolated from primary sites, for certain types of cancer including liver, lung and pancreas cancer. In contrast, for cancer types such as ovarian and skin cancer, human cancer cell lines originated from primary tumors have increased metastatic potential in mice, compared to human cancer cell lines originated from metastatic sites. This preliminary analysis points that the potential of metastases to further metastasize compared to that of primary tumors might be cancer type-dependent, and further research is needed to understand why certain cancer cell lines isolated from metastatic sites are more likely to spread to other organs.

关键词： primary cutaneous peripheral T-Cell lymphoma   CD8 lymphoma   cutaneous lymphoma  

摘要： Acral CD8(+) lymphoma is a provisional entity in the latest edition of the WHO Lymphoma Classification and is associated with a highly specific dot-like pattern of immunohistochemical expression of CD68. We report a case of an ulcerated solitary cutaneous lesion arising on the forehead of an adult man, which had a CD8(+) cytotoxic phenotype and areas of dot-like CD68 positivity, but with a number of features that significantly detracted from the classically described acral CD8(+) lymphoma. The nosological status of the lesion is discussed with respect to a preferred diagnosis of peripheral T-cell lymphoma, not otherwise specified.

关键词： astrocytes   connexin 30   excitation‐   inhibition balance   hippocampus   neuroglial interactions   patch‐   clamp   synaptic transmission  

摘要： Astrocytes play important roles in brain function via dynamic structural and functional interactions with neurons. Yet the underlying mechanisms remain poorly defined. A typical feature of astrocytes is the high expression of connexins, which mediate their extensive intercellular communication and regulate their structural properties. In particular, connexin 30 (Cx30), one of the two connexins abundantly expressed by astrocytes, was recently shown to be a critical regulator of excitatory synaptic transmission by controlling the astroglial coverage of synapses. However, the role of Cx30 in the regulation of inhibitory synaptic transmission and excitatory/inhibitory balance remains elusive. Here, we investigated the role of astroglial Cx30 on the electrophysiological and morphological properties of five classes of hippocampal CA1 stratum oriens and pyramidale neurons, defined by the unsupervised Ward's clustering. Using Cx30 knockout mice, we found that Cx30 alters specific properties of some subsets of CA1 interneurons, such as resting membrane potential and sag ratio, while other parameters, such as action potential threshold and saturation frequency, were more frequently altered among the different classes of neurons. The excitation-inhibition balance was also differentially and selectively modulated among the different neuron subtypes. Only slight morphological differences were observed on reconstructed neurons. Altogether, these data indicate that Cx30 differentially alters the electrophysiological and morphological properties of hippocampal cell populations, and modulates both their excitatory and inhibitory inputs. Astrocytes, via Cx30, are thus active modulators of both excitatory and inhibitory synapses in the hippocampus.

关键词： kidney   renal primary tubular epithelial cells   collagenase   perfusion   primary culture  

摘要： Kidney diseases are becoming an emerging public health problem. In order to further explore the etiology of various kidney diseases, we improved the methods of isolation of primary cultures of mouse renal tubular epithelial cells. At the first stage, the kidneys were perfused with collagenase solution. To this end, the superior mesenteric artery, celiac artery and thoracic aorta were ligated and perfusion was performed through the abdominal aorta. Then, the cells were isolated ex vivo and their integrity, purity, viability, and concentration were evaluated. The proposed cost-effective and simple method provides high purity and high concentration of primary renal epithelial cells for molecular biology studies of the kidneys.

关键词： adjuvant chemotherapy   adjuvant radiation therapy   cutaneous squamous cell carcinoma   immunotherapy   targeted therapy  

摘要： Standard of care for high-risk cutaneous squamous cell carcinoma (cSCC) is surgical excision of the primary lesion with clear margins when possible, and additional resection of positive margins when feasible. Even with negative margins, certain high-risk factors warrant consideration of adjuvant therapy. However, which patients might benefit from adjuvant therapy is unclear, and supporting evidence is conflicting and limited to mostly small retrospective cohorts. Here, we review literature from the last decade regarding adjuvant radiation therapy and systemic therapy in high-risk cSCC, including recent and current trials and the role of immune checkpoint inhibitors. We demonstrate evidence gaps in adjuvant therapy for high-risk cSCC and the need for prognostic tools, such as gene expression profiling, to guide patient selection. More large-cohort clinical studies are needed for collecting high-quality, evidence-based data for determining which patients with high-risk cSCC may benefit from adjuvant therapy and which therapy is most appropriate for patient management.

关键词： 庭院   阳台  

ISBN: (纸本)9787111688631

摘要： 本书通过图文解说的形式，对阳台、露台、小庭院设计中的重要知识点进行深入解析，观点表达具体，文字通俗易懂。以图文结合的编写形式，能够在较大程度上让读者理解要点。书中配有大量精美的案例图片，十分具有代表性，细致到地面材质、绿植种类等。从阳台到露台，再到庭院，手把手教读者打造梦想中的都市花园，满足人们对生活环境的绿化需求。

关键词： cancer   chimeric antigen receptor   IKK epsilon   immunotherapy   lentivirus   natural killer   TBK1   VSV-G  

摘要： Background aims: Vesicular stomatitis virus G (VSV-G)-pseudotyped lentiviral vectors (LVs) are widely used to reliably generate genetically modified, clinical-grade T-cell products. However, the results of genetically modifying natural killer (NK) cells with VSV-G LVs have been variable. The authors explored whether inhibition of the IKK-related protein kinases TBK1 and IKK epsilon, key signaling molecules of the endosomal TLR4 pathway, which is activated by VSV-G, would enable the reliable transduction of NK cells by VSV-G LVs. Methods: The authors activated NK cells from peripheral blood mononuclear cells using standard procedures and transduced them with VSV-G LVs encoding a marker gene (yellow fluorescent protein [YFP]) or functional genes (chimeric antigen receptors [CARs], co-stimulatory molecules) in the presence of three TBK1/IKK epsilon inhibitors (MRT67307, BX-795, amlexanox). NK cell transduction was evaluated by flow cytometry and/or western blot and the functionality of expressed CARs was evaluated in vitro. Results: Blocking TBK1/IKK epsilon during transduction of NK cells enabled their efficient transduction by VSV-G LVs as judged by YFPexpression of 40-50%, with half maximal effective concentrations of 1.1 mu M (MRT67307), 5 mu M (BX-795) and 24.8 mu M (amlexanox). Focusing on MRT67307, the authors successfully generated NK cells expressing CD19-CARs or HER2-CARs with an inducible co-stimulatory molecule. CAR NK cells exhibited increased cytolytic activity and ability to produce cytokines in comparison to untreated controls, confirming CAR functionality. Conclusions: The authors demonstrate that inhibition of TBK1/IKK epsilon enables the reliable generation of genetically modified NK cells using VSV-G LVs. The authors' protocol can be readily adapted to generate clinical-grade NK cells and thus has the potential to facilitate the clinical evaluation of genetically modified NK cell-based therapeutics in the future. (C) 2021 International Society for C

关键词： basal insulin   clinical trial   continuous glucose monitoring (CGM)   insulin therapy   type 2 diabetes  

摘要： Aim To evaluate the efficacy and safety of basal-bolus insulin therapy in managing glycaemia during fasting periods in hospitalized patients with type 2 diabetes. Materials and Methods We performed a post hoc analysis of two prospective, uncontrolled interventional trials that applied electronic decision support system-guided basal-bolus (meal-related and correction) insulin therapy. We searched for fasting periods (invasive or diagnostic procedures, medical condition) during inpatient stays. In a mixed model analysis, patients & apos;glucose levels and insulin doses on days with regular food intake were compared with days with fasting periods. Results Out of 249 patients, 115 patients (33.9% female, age 68.3 +/- 10.3 years, diabetes duration 15.1 +/- 10.9 years, body mass index 30.1 +/- 5.4 kg/m(2), HbA1c 69 +/- 20 mmol/mol) had 194 days with fasting periods. Mean daily blood glucose (BG) was lower (modelled difference [ModDiff]: -0.5 +/- 0.2 mmol/L, P = .006), and the proportion of glucose values within the target range (3.9-10.0 mmol/L) increased on days with fasting periods compared with days with regular food intake (ModDiff: +0.06 +/- 0.02, P = .005). Glycaemic control on fasting days was driven by a reduction in daily bolus insulin doses (ModDiff: -11.0 +/- 0.9 IU, P < .001), while basal insulin was similar (ModDiff: -1.1 +/- 0.6 IU, P = .082) compared with non-fasting days. Regarding hypoglycaemic events (BG < 3.9 mmol/L), there was no difference between fasting and non-fasting days (chi(2) 0.9% vs. 1.7%, P = .174). Conclusions When using well-titrated basal-bolus insulin therapy in hospitalized patients with type 2 diabetes, the basal insulin dose does not require adjustment during fasting periods to achieve safe glycaemic control, provided meal-related bolus insulin is omitted and correction bolus insulin is tailored to glucose levels.

关键词： bone formation   cellular heterogeneity   osteoblasts   single-cell RNA sequencing  

摘要： Human osteoblasts are multifunctional bone cells, which play essential roles in bone formation, angiogenesis regulation, as well as maintenance of hematopoiesis. However, the categorization of primary osteoblast subtypes in vivo in humans has not yet been achieved. Here, we used single-cell RNA sequencing (scRNA-seq) to perform a systematic cellular taxonomy dissection of freshly isolated human osteoblasts from one 31-year-old male with osteoarthritis and osteopenia after hip replacement. Based on the gene expression patterns and cell lineage reconstruction, we identified three distinct cell clusters including preosteoblasts, mature osteoblasts, and an undetermined rare osteoblast subpopulation. This novel subtype was found to be the major source of the nuclear receptor subfamily 4 group A member 1 and 2 (NR4A1 and NR4A2) in primary osteoblasts, and the expression of NR4A1 was confirmed by immunofluorescence staining on mouse osteoblasts in vivo. Trajectory inference analysis suggested that the undetermined cluster, together with the preosteoblasts, are involved in the regulation of osteoblastogenesis and also give rise to mature osteoblasts. Investigation of the biological processes and signaling pathways enriched in each subpopulation revealed that in addition to bone formation, preosteoblasts and undetermined osteoblasts may also regulate both angiogenesis and hemopoiesis. Finally, we demonstrated that there are systematic differences between the transcriptional profiles of human and mouse osteoblasts, highlighting the necessity for studying bone physiological processes in humans rather than solely relying on mouse models. Our findings provide novel insights into the cellular heterogeneity and potential biological functions of human primary osteoblasts at the single-cell level © 2021 Gong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and repr