EPLBD is an effective and safe method for the removal of large or difficult common bile stones. EPLBD should be considered as an alternative to EST for patients in whom EST could not be routinely performed. Based on EPLBD causing fewer cases of hemorrhaging, EPLBD is also recommended for removal of large or difficult common bile duct stones in patients with an underlying coagulopathy or need for anticoagulation following ERCP. The long-term prognosis of EPLBD need to be further investigated.
Neural stem cells (NSCs) are capable of self-renewal and are multipotent. Transplantation of NSCs may represent a promising approach for treating neurodegenerative disorders associated with cognitive decline, such as Alzheimer disease (AD) characterized by extensive loss of neurons. In this study, we investigated the effect of NSC transplantation on cognitive function in the amyloid precursor protein/presenilin-1 (APP/PS1) transgenic mouse, an AD mouse model with age-dependent cognitive deficits. We found that NSCs bilaterally transplanted into hippocampal regions improved spatial learning and memory function in these mice, but did not alter Aβ pathology. Immunohistochemical analyses determined that NSCs proliferated, migrated, and differentiated into three neuronal cell types. The improvement in cognitive function was correlated with enhanced long-term potentiation (LTP) and an increase in the neuron expression of proteins related to cognitive function: N-methyl-D-aspartate (NMDA) 2B unit, synaptophysin (SYP), protein kinase C ζ subtypes (PKCζ), tyrosine receptor kinase B (TrkB), and brain-derived neurotrophic factor (BDNF). Taken together, our data indicated that injected NSCs can rescue cognitive deficits in APP/PS1 transgenic mice by replacing neuronal cell types expressing multiple cognition-related proteins that enhance LTP.
Let-7i-3p and miR-595 could be potential, non-invasive biomarkers for the accurate early detection and diagnosis of MP, which may result in improved clinical management.
Osteoclasts originate from bone marrow monocyte/macrophage lineage cells, which are important for bone health. Class A scavenger receptor (SR-A) is a multifunctional molecule that functions during differentiation of monocyte into macrophages and osteoclasts. To further characterize the role of SR-A in osteoclasts, we used the murine tooth movement model (TM) and the murine anterior cruciate ligament transection model of osteoarthritis (ACLT OA). In these two models the bones involved are of different origin and have different properties. Bone resorption was decreased in SR-A-/- mice compared to SR-A+/+ mice. Further evaluation showed that the number of multinucleated osteoclasts in SR-A-/- mice, compared to SR-A+/+ mice, was significantly decreased both in vivo and in vitro. The levels of interleukin-6 (IL-6) produced by osteoclasts were reduced in SR-A-/- mice compared to SR-A+/+ mice. In the in vitro marrow-derived osteoclast formation assay and in both mouse models, osteoclastogenesis was restored to normal in SR-A-/- mice by administration of recombinant murine IL-6. Moreover, neutralization of IL-6 reduced the number of osteoclasts formed in SR-A+/+ mice of TM model. Both extracellular signal-regulated kinase (ERK) and c-Jun N-terminal protein kinase (JNK), but not p38, signaling pathways were downregulated in receptor activator of nuclear factor-κB ligand (RANKL)-stimulated SR-A-/- osteoclasts. Importantly, when treated with either ERK or JNK inhibitor, the numbers of osteoclasts generated from RANKL-induced bone marrow derived-macrophages of SR-A+/+ mice, and their IL-6 production, were significantly decreased. This suggests that SR-A activates the ERK and JNK signaling pathways, and promotes production of IL-6 by osteoclasts to further stimulate osteoclast formation.
Nanodrug-delivery systems modified
with targeting molecules allow antitumor drugs to localize to tumor
sites efficiently. CD147 protein is expressed highly on hepatoma cells. Firstly, we synthesized magnetothermally responsive nanocarriers/doxorubicin (MTRN/DOX) which was composed of manganese zinc (Mn-Zn) ferrite magnetic nanoparticles, amphiphilic and thermosensitivity copolymer drug carriers together with DOX. Then CD147-MTRN/DOX was formed with MTRN/DOX and monoclonal antibody that specifically binds to CD147 protein. It could
target hepatoma cells actively and improve the DOX concentration in
the tumor sites. Subsequently, an external alternating magnetic field
elevated the temperature of the thermomagnetic particles, resulting
in structural changes in the thermosensitive copolymer drug carriers,
thereby releasing DOX. Hence, CD147-MTRN/DOX could enhance the responsiveness
of hepatoma cells to the pre-existing chemotherapy drugs owing to
active targeting combined synergistically with thermotherapy and chemotherapy,
which has more significant anticancer effects than MTRN/DOX.
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