MAPK Usage in Periodontal Disease Progression

In periodontal disease, host recognition of bacterial constituents, including lipopolysaccharide (LPS), induces p38 MAPK activation and subsequent inflammatory cytokine expression, favoring osteoclastogenesis and increased net bone resorption in the local periodontal environment. In this paper, we discuss evidence that the p38/MAPK-activated protein kinase-2 (MK2) signaling axis is needed for periodontal disease progression: an orally administered p38α inhibitor reduced the progression of experimental periodontal bone loss by reducing inflammation and cytokine expression. Subsequently, the significance of p38 signaling was confirmed with RNA interference to attenuate MK2-reduced cytokine expression and LPS-induced alveolar bone loss. MAPK phosphatase-1 (MKP-1), a negative regulator of MAPK activation, was also critical for periodontal disease progression. In MPK-1-deficient mice, p38-sustained activation increased osteoclast formation and bone loss, whereas MKP-1 overexpression dampened p38 signaling and subsequent cytokine expression. Finally, overexpression of the p38/MK2 target RNA-binding tristetraprolin (TTP) decreased mRNA stability of key inflammatory cytokines at the posttranscriptional level, thereby protecting against periodontal inflammation. Collectively, these studies highlight the importance of p38 MAPK signaling in immune cytokine production and periodontal disease progression

Mannose‐Modified Multi‐Walled Carbon Nanotubes as a Delivery Nanovector Optimizing the Antigen Presentation of Dendritic Cells

Dendritic cells (DCs) based cancer immunotherapy is largely dependent on adequate antigen delivery and efficient induction of DCs maturation to produce sufficient antigen presentation and ultimately lead to substantial activation of tumor‐specific CD8+ T cells. Carbon nanotubes (CNTs) have attracted great attention in biomedicine because of their unique physicochemical properties. In order to effectively deliver tumor antigens to DCs and trigger a strong anti‐tumor immune response, herein, a specific DCs target delivery system was assembled by using multi‐walled carbon nanotubes modified with mannose which can specifically bind to the mannose receptor on DCs membrane. Ovalbumin (OVA) as a model antigen, could be adsorbed on the surface of mannose modified multi‐walled carbon nanotubes (Man‐MWCNTs) with a large drug loading content. This nanotube‐antigen complex showed low cytotoxicity to DCs and was efficiently engulfed by DCs to induce DCs maturation and cytokine release in vitro, indicating that it could be a potent antigen‐adjuvant nanovector of efficient antigen delivery for therapeutic purpose.Perfectly delivered! Mannose‐modified multi‐walled carbon nanotubes (Man‐MWCNTs) could efficiently deliver a large amount of antigen to bone marrow derived dendritic cells (DCs) through ligand/receptor interactions of mannose, inducing enhanced BMDCs maturation and cytokines secretion.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150607/1/open201900126-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150607/2/open201900126.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150607/3/open201900126_am.pd

MiR-23a Regulates Skin Langerhans Cell Phagocytosis and Inflammation-Induced Langerhans Cell Repopulation

Langerhans cells (LCs) are skin-resident macrophage that act similarly to dendritic cells for controlling adaptive immunity and immune tolerance in the skin, and they are key players in the development of numerous skin diseases. While TGF-β and related downstream signaling pathways are known to control numerous aspects of LC biology, little is known about the epigenetic signals that coordinate cell signaling during LC ontogeny, maintenance, and function. Our previous studies in a total miRNA deletion mouse model showed that miRNAs are critically involved in embryonic LC development and postnatal LC homeostasis; however, the specific miRNA(s) that regulate LCs remain unknown. miR-23a is the first member of the miR-23a-27a-24-2 cluster, a direct downstream target of PU.1 and TGF-b, which regulate the determination of myeloid versus lymphoid fates. Therefore, we used a myeloid-specific miR-23a deletion mouse model to explore whether and how miR-23a affects LC ontogeny and function in the skin. We observed the indispensable role of miR-23a in LC antigen uptake and inflammation-induced LC epidermal repopulation; however, embryonic LC development and postnatal homeostasis were not affected by cells lacking miR23a. Our results suggest that miR-23a controls LC phagocytosis by targeting molecules that regulate efferocytosis and endocytosis, whereas miR-23a promotes homeostasis in bone marrow-derived LCs that repopulate the skin after inflammatory insult by targeting Fas and Bcl-2 family proapoptotic molecules. Collectively, the context-dependent regulatory role of miR-23a in LCs represents an extra-epigenetic layer that incorporates TGF-b- and PU.1-mediated regulation during steady-state and inflammation-induced repopulation

Recurrent paratesticular giant liposarcoma: A case report and literature review

BackgroundPrimary paratesticular liposarcoma is rarely diagnosed among urinary tumors. In this study, through the retrospective analysis of clinical data and literature review, a case of recurrent paratesticular liposarcoma with lymph node metastasis after radical resection has been reported to explore novel strategies for the diagnosis, treatment and prognosis of this rare disease.Case summaryThe present case involved a patient who was misdiagnosed as a left inguinal hernia for the first time two years ago, but was later diagnosed as mixed liposarcoma by using postoperative pathology. Currently, he is readmitted to the hospital with a recurrence of the left scrotal mass for more than 1 year. Combined with the patient's past medical history, we performed radical resection of the left inguinal and scrotal tumors and lymphadenectomy of left femoral vein. The postoperative pathology indicated that well-differentiated liposarcoma was accompanied by mucinous liposarcoma (about 20%), and lymph node metastasis of left femoral vein both of which occurred at the same time. After the operation, we recommended the patient to receive further radiation therapy, but the patient and his family refused, hence we followed up the patient closely for a long time. During the recent follow-up, the patient reported no complaints of discomfort, and no recurrence of mass in the left scrotum and groin area.ConclusionAfter conducting extensive review of literature, we conclude that radical resection remains the key to treat primary paratesticular liposarcoma, while the significance of the lymph node metastasis is still unclear. The potential effects of postoperative adjuvant therapy depends on the pathological type, and hence close follow-up observation is essential

Pro-angiogenic Role of Danqi Pill Through Activating Fatty Acids Oxidation Pathway Against Coronary Artery Disease

Coronary artery disease (CAD) is one of the leading causes of deaths worldwide. Energy metabolism disorders, including a reduction in fatty acids oxidation and upregulation of glycolysis pathway, are involved in the process of CAD. Therapeutic angiogenesis has become a promising treatment for CAD. Traditional Chinese medicines, such as Danqi Pill (DQP), have been proven to be effective in treating CAD in China for many years. However, the pro-angiogenic effects of DQP based on fatty acids oxidation are still unknown and the mechanism is worthy of investigation. In this study, left anterior descending (LAD) coronary artery was ligated to induce the CAD models in vivo, and cardiac functions were examined using echocardiography. Human umbilical vein endothelial cells (HUVEC) were subjected to H2O2-induced oxidative stress in vitro. The effects of DQP on CAD rat models and in vitro HUVEC were detected. Our results showed that DQP had cardio-protective effects in rat model. The intensity of capillaries in the marginal area of infarction of the rat heart was increased remarkably in DQP group, and the expression of PPARα and VEGF-2 were increased. The key enzymes involved in the transportation and intake of fatty acids, including CPT1A and CD36, both increased. In H2O2-induced endothelial cells injury models, DQP also showed protective roles and promoted capillary-like tube formation. DQP up-regulated key enzymes in fatty acids oxidation in H2O2-treated HUVEC. In addition, inhibition of CPT1A compromised the pro-angiogenic effects of DQP. In conclusion, fatty acids oxidation axis PPARα-CD36-CPT1A was involved in the pro-angiogenic roles of DQP against CAD. Cardiac CPT1A may serve as a target in therapeutic angiogenesis in clinics

Socio-spatial differentiation and residential segregation in the Chinese city based on the 2000 community-level census data: A case study of the inner city of Nanjing

Socio-spatial differentiation and residential segregation have been studied extensively in numerous cities and have contributed significantly to the understanding of urban spatial and social structures. Analyses of diverse data sets at varied spatial scales have supported the development of theoretical frameworks. However, the majority of Chinese case studies published in recent decades were dominantly based on either non-spatial data or population census data at sub-district (or jiedao in Chinese) level. These analyses have been limited through using low-resolution aggregate data resulting in incomplete or biased findings. This paper aims to examine the fine-scale socio-spatial structure of the inner city of Nanjing using the fifth population census data of 2000 at the lowest spatial scale – community (or juweihui in Chinese) level. Our findings reveal that the policies of the socialist era and the initial outcomes of the introduction of a free market, particularly with regard to the creation of new elite spaces within the inner city, have shaped a complex pattern of socio-spatial differentiation and residential segregation

Challenges in QCD matter physics - The Compressed Baryonic Matter experiment at FAIR

Substantial experimental and theoretical efforts worldwide are devoted to explore the phase diagram of strongly interacting matter. At LHC and top RHIC energies, QCD matter is studied at very high temperatures and nearly vanishing net-baryon densities. There is evidence that a Quark-Gluon-Plasma (QGP) was created at experiments at RHIC and LHC. The transition from the QGP back to the hadron gas is found to be a smooth cross over. For larger net-baryon densities and lower temperatures, it is expected that the QCD phase diagram exhibits a rich structure, such as a first-order phase transition between hadronic and partonic matter which terminates in a critical point, or exotic phases like quarkyonic matter. The discovery of these landmarks would be a breakthrough in our understanding of the strong interaction and is therefore in the focus of various high-energy heavy-ion research programs. The Compressed Baryonic Matter (CBM) experiment at FAIR will play a unique role in the exploration of the QCD phase diagram in the region of high net-baryon densities, because it is designed to run at unprecedented interaction rates. High-rate operation is the key prerequisite for high-precision measurements of multi-differential observables and of rare diagnostic probes which are sensitive to the dense phase of the nuclear fireball. The goal of the CBM experiment at SIS100 (sqrt(s_NN) = 2.7 - 4.9 GeV) is to discover fundamental properties of QCD matter: the phase structure at large baryon-chemical potentials (mu_B > 500 MeV), effects of chiral symmetry, and the equation-of-state at high density as it is expected to occur in the core of neutron stars. In this article, we review the motivation for and the physics programme of CBM, including activities before the start of data taking in 2022, in the context of the worldwide efforts to explore high-density QCD matter.Comment: 15 pages, 11 figures. Published in European Physical Journal