Explore the vast range of titles available.

Background The fixation strength of bone screws depends on bone mineral density (BMD), so it is important to evaluate bone strength at fracture sites. Few studies have investigated BMD in the pelvis. The aims of this study were to measure the regional Hounsfield unit (HU) values in the cancellous bone of the acetabulum and pelvic ring and to compare these values between young and older patients. Methods This study enrolled young patients with high-energy trauma (aged 20–44 years; young group) and older patients with low-energy trauma (aged 65–89 years; older group). Patients without pelvic computed tomography (CT) scans, those with pelvic bone implants, and those who died were excluded. The HU values on the contralateral (non-fractured) side of the pelvis were measured on CT scans. The CT data were divided into 7 areas: the pubic bone, the anterior and posterior walls and roof of the acetabulum, the ischial tuberosity, the body of the ilium, and the third lumbar vertebra. The HU values in each area were compared between the young and older groups. Results Sixty-one young patients and 154 older patients were included in the study. The highest HU value was in the roof of the acetabulum regardless of age and sex. HU values were significantly higher in the ischial tuberosity and body of the ilium and lower in the pubic bone and anterior wall. The HU values in all pelvic areas were significantly lower in the older group than in the young group, especially in the anterior area. Conclusions HU values in the 6 pelvic areas were not uniform and were strongly related to load distribution. The HU distribution and age-related differences could explain the characteristic causes and patterns of acetabular fractures in the older and may help in surgical treatment.

Background Sarcopenia is characterized by the loss of skeletal muscle mass and strength and is associated with poor prognosis in patients with chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS) exposure, a major cause for COPD, induces mitochondrial damage, which has been implicated in sarcopenia pathogenesis. The current study sought to examine the involvement of insufficient Parkin‐mediated mitophagy, a mitochondrion‐selective autophagy, in the mechanisms by which dysfunctional mitochondria accumulate with excessive reactive oxygen species (ROS) production in the development of COPD‐related sarcopenia. Methods The involvement of Parkin‐mediated mitophagy was examined using in vitro models of myotube formation, in vivo CS‐exposure model using Parkin−/− mice, and human muscle samples from patients with COPD‐related sarcopenia. Results Cigarette smoke extract (CSE) induced myotube atrophy with concomitant 30% reduction in Parkin expression levels (P < 0.05). Parkin‐mediated mitophagy regulated myotube atrophy by modulating mitochondrial damage and mitochondrial ROS production. Increased mitochondrial ROS was responsible for myotube atrophy by activating Muscle Ring Finger 1 (MuRF‐1)‐mediated myosin heavy chain (MHC) degradation. Parkin−/− mice with prolonged CS exposure showed enhanced limb muscle atrophy with a 31.7% reduction in limb muscle weights (P < 0.01) and 2.3 times greater MuRF‐1 expression (P < 0.01) compared with wild‐type mice with concomitant accumulation of damaged mitochondria and oxidative modifications in 4HNE expression. Patients with COPD‐related sarcopenia exhibited significantly reduced Parkin but increased MuRF‐1 protein levels (35% lower and 2.5 times greater protein levels compared with control patients, P < 0.01 and P < 0.05, respectively) and damaged mitochondria accumulation demonstrated in muscles. Electric pulse stimulation‐induced muscle contraction prevented CSE‐induced MHC reduction by maintaining Parkin levels in myotubes. Conclusions Taken together, COPD‐related sarcopenia can be attributed to insufficient Parkin‐mediated mitophagy and increased mitochondrial ROS causing enhanced muscle atrophy through MuRF‐1 activation, which may be at least partly preventable through optimal physical exercise.

Background Several retrospective studies have reported spine–femur discordance in bone mineral density (BMD) values. However, the average age of individuals in these studies was the mid-50s, which is younger than the typical age of individuals requiring treatment for primary osteoporosis. Therefore, we aimed to investigate factors associated with discordance in the percentage of young adult mean (YAM) between the lumbar spine and femoral neck in the elderly population. Methods We evaluated 4549 dual-energy X-ray absorptiometry (DXA) measurements obtained from 2161 patients (269 men and 1892 women) between January 2014 and December 2017 at our hospital. For individuals with more than one eligible set of measurements, the first record was used. We investigated each patient’s age, sex, body mass index, current smoking status, alcohol consumption, use of steroids, presence of diabetes mellitus, and presence of rheumatoid arthritis. Results The mean age of the patients was 76.4 ± 8.9 years. Older age ( p  <  0.001), male sex ( p  <  0.001), and diabetes mellitus ( p  = 0.007) were significantly associated with spine–femur discordance in the percentage of YAM. Conclusion The frequency and magnitude of spine–femur discordance in the percentage of YAM from DXA scans increased with age. Notably, more than 77.4% of patients in their 90s had spine–femur discordance > 10% of YAM. Furthermore, the frequency of spine–femur discordance was higher in men and in patients with diabetes mellitus, suggesting that the percentage of YAM at the lumbar spine may not be reliable for diagnosis of osteoporosis in patients with these factors.

Prostaglandin E-major urinary metabolite (PGE-MUM) is a urinary biomarker reflecting ulcerative colitis (UC) activity. This prospective observational study aimed to evaluate the usefulness of PGE-MUM via rapid chemiluminescent enzyme immunoassay in detecting endoscopic remission (ER) and histologic remission (HR) in pediatric UC (6–16 years) in comparison with fecal calprotectin (FCP). ER and HR were defined as Mayo endoscopic score (MES) of 0 and Matts’ histological grades (Matts) of 1 or 2, respectively. A total of 104 UC and 39 functional gastrointestinal disorder (FGID) were analyzed. PGE-MUM levels were significantly higher in the UC group than in the FGID group ( P  < 0.001). FCP levels were significantly elevated in the group without ER and HR than in the group with ER and HR ( P  < 0.001 and P  = 0.001), whereas PGE-MUM levels were significantly higher in the group without ER compared to the group with ER ( P  < 0.001). No significant differences were noted in the AUCs for PGE-MUM and FCP in detecting ER and HR. Although PGE-MUM was inferior to FCP for the detection of HR, it might have the potential for application as a biomarker of endoscopic activity in pediatric UC owing to its noninvasive and rapid method.

A 91-year-old man had a node and erythema in the anal area resistant to treatment. A biopsy of the node in the anus showed atypical cells developing as Paget’s disease, and staining revealed that the cells were CK7-positive, CK20-positive, and GCDFP15-negative. Therefore, tumor invasion with pagetoid spread (PS) from the anus to the skin was suspected, and the patient was referred to our department for a close examination and surgical treatment. Lower gastrointestinal endoscopy showed edematous, hemorrhagic mucosa in the anal canal, and he was diagnosed with adenocarcinoma via a biopsy. Additionally, redness and swelling with white moss were observed on the skin around the anus. Biopsy showed that Paget cells were diffusely present in the epithelium, and an image of squamous cell carcinoma directly under the epithelium was obtained. Taken together, the patient was diagnosed with the invasion of anal canal cancer with PS to the skin, and we performed laparoscopic abdominoperineal resection and skin carcinoma resection in the perineum. The histopathological analysis showed adenocarcinoma invading the external anal sphincter and subcutaneous adipose tissue in the vicinity of the pectinate line of the anal canal. Pagetoid spread of the adenocarcinoma was observed in the epidermis, and the open portion was slightly invaded up to the rectal mucosa. The anal skin region of the adenocarcinoma partially continued to the hair follicles, and it was complicated by squamous cell carcinoma invading the dermis. There are a few reports of anal canal cancer with PS, and the coexistence of adenocarcinoma and squamous cell carcinoma, as seen in the present case, is rare. We report our case together with relevant literature.

Osteolytic lesions are rapidly progressive during the terminal stages of myeloma, and the bone pain or bone fracture that occurs at these lesions decreases the patients' quality of life to a notable degree. In relation to the etiology of this bone destruction, it has been reported recently that MIP-1 alpha , produced in large amounts in myeloma patients, acts indirectly on osteoclastic precursor cells, and activates osteoclasts by way of bone-marrow stromal cells or osteoblasts, although the details of this process remain obscure. In the present study, our group investigated the mechanism by which RANKL expression is induced by MIP-1 alpha and the effects of MIP-1 alpha on the activation of osteoclasts. RANKL mRNA and RANKL protein expressions increased in both ST2 cells and MC3T3-E1 cells in a MIP-1 alpha concentration-dependent manner. RANKL mRNA expression began to increase at 1 h after the addition of MIP-1 alpha ; the increase became remarkable at 2 h, and continuous expression was observed subsequently. Both ST2 and MC3T3-E1 cells showed similar levels of increased RANKL protein expression at 1, 2, and 3 days after the addition of MIP-1 alpha . After the addition of MIP-1 alpha , the amount of phosphorylated ERK1/2 and Akt protein expressions showed an increase, as compared to the corresponding amount in the control group. On the other hand, the amount of phosphorylated p38MAPK protein expression showed a decrease from the amount in the control group after the addition of MIP-1 alpha . U0126 (a MEK1/2 inhibitor) or LY294002 (a PI3K inhibitor) was added to ST2 and MC3T3-E1 cells, and was found to inhibit RANKL mRNA and RANKL protein expression in these cells. When SB203580, a p38MAPK inhibitor, was added, RANKL mRNA and RANKL protein expression were increased in these cells. MIP-1 alpha was found to promote osteoclastic differentiation of C7 cells, an osteoclastic precursor cell line, in a MIP-1 alpha concentration-dependent manner. MIP-1 alpha promoted differentiation into osteoclasts more extensively in C7 cells incubated together with ST2 and MC3T3-E1 cells than in C7 cells incubated alone. These results suggested that MIP-1 alpha directly acts on the osteoclastic precursor cells and induces osteoclastic differentiation. This substance also indirectly induces osteoclastic differentiation through the promotion of RANKL expression in bone-marrow stromal cells and osteoblasts. The findings of this investigation suggested that activation of the MEK/ERK and the PI3K/Akt pathways and inhibition of p38MAPK pathway were involved in RANKL expression induced by MIP-1 alpha in bone-marrow stromal cells and osteoblasts. This finding may be useful in the development of an osteoclastic inhibitor that targets intracellular signaling factors.

Protein kinase C (PKC) has been shown to be a signal transducer during tumorigenesis, tumor cell invasion, and metastasis. Recent studies have reported that the PKC inhibitor, 7-hydroxystaurosporine, inhibits tumor cell invasion. However, the molecular mechanisms of this inhibition of invasion and metastasis are not well understood. In the present study, we attempt to clarify the mechanism by which H7, a PKC inhibitor, inhibits tumor cell invasion and metastasis in the melanoma cell line B16BL6. It was found that H7 inhibits B16BL6 cell invasion and metastasis. We also observed that H7 inhibits the mRNA expression and protein activities of matrix metalloproteinase (MMP)-1, -2, -9 and MT1-MMP. Furthermore, H7 suppresses phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2). However, other signal transduction factors, such as p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase 1/2 (JNK1/2), were unaffected. Moreover, U0126, a MEK1/2 inhibitor, also inhibited B16BL6 cell invasion and metastasis, as well as the mRNA expression and protein activities of MMP-1, -2, -9 and MT1-MMP. This indicates that H7 inhibits signal transduction through the PKC/MEK/ERK pathway, thereby inhibiting B16BL6 cell invasion and metastasis. These results suggest that PKC inhibitors have potential clinical applications in the treatment of tumor cell metastasis.

Osteolytic lesions are rapidly progressive during the terminal stages of myeloma, and the bone pain or bone fracture that occurs at these lesions decreases the patients' quality of life to a notable degree. In relation to the etiology of this bone destruction, it has been reported recently that MIP-1a, produced in large amounts in myeloma patients, acts indirectly on osteoclastic precursor cells, and activates osteoclasts by way of bone-marrow stromal cells or osteoblasts, although the details of this process remain obscure. In the present study, our group investigated the mechanism by which RANKL expression is induced by MIP-1a and the effects of MIP-1a on the activation of osteoclasts. RANKL mRNA and RANKL protein expressions increased in both ST2 cells and MC3T3-E1 cells in a MIP-1a concentration-dependent manner. RANKL mRNA expression began to increase at 1h after the addition of MIP-1a; the increase became remarkable at 2h, and continuous expression was observed subsequently. Both ST2 and MC3T3-E1 cells showed similar levels of increased RANKL protein expression at 1, 2, and 3days after the addition of MIP-1a. After the addition of MIP-1a, the amount of phosphorylated ERK1/2 and Akt protein expressions showed an increase, as compared to the corresponding amount in the control group. On the other hand, the amount of phosphorylated p38MAPK protein expression showed a decrease from the amount in the control group after the addition of MIP-1a. U0126 (a MEK1/2 inhibitor) or LY294002 (a PI3K inhibitor) was added to ST2 and MC3T3-E1 cells, and was found to inhibit RANKL mRNA and RANKL protein expression in these cells. When SB203580, a p38MAPK inhibitor, was added, RANKL mRNA and RANKL protein expression were increased in these cells. MIP-1a was found to promote osteoclastic differentiation of C7 cells, an osteoclastic precursor cell line, in a MIP-1a concentration-dependent manner. MIP-1a promoted differentiation into osteoclasts more extensively in C7 cells incubated together with ST2 and MC3T3-E1 cells than in C7 cells incubated alone. These results suggested that MIP-1a directly acts on the osteoclastic precursor cells and induces osteoclastic differentiation. This substance also indirectly induces osteoclastic differentiation through the promotion of RANKL expression in bone-marrow stromal cells and osteoblasts. The findings of this investigation suggested that activation of the MEK/ERK and the PI3K/Akt pathways and inhibition of p38MAPK pathway were involved in RANKL expression induced by MIP-1a in bone-marrow stromal cells and osteoblasts. This finding may be useful in the development of an osteoclastic inhibitor that targets intracellular signaling factors.