Synaptosomal associated protein of 23 kDa (SNAP23), a plasma membrane-localized soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE), is a ubiquitously expressed protein that is generally involved in fusion of the plasma membrane and secretory or endosomal recycling vesicles during several types of exocytosis. SNAP23 is expressed in phagocytes, such as neutrophils, macrophages, and dendritic cells, and functions in both exocytosis and phagocytosis. This review focuses on the function of SNAP23 in immunoglobulin G Fc receptor-mediated phagocytosis by macrophages. SNAP23 and its partner SNAREs mediate fusion of the plasma membrane with intracellular organelles or vesicles to form phagosomes as well as the fusion of phagosomes with endosomes or lysosomes to induce phagosome maturation, characterized by reactive oxygen species production and acidification. During these processes, SNAP23 function is regulated by phosphorylation. In addition, microtubule-associated protein 1A/1B light chain 3 (LC3)-associated phagocytosis, which tightly promotes or suppresses phagosome maturation depending on the foreign target, requires SNAP23 function. SNAP23 that is enriched on the phagosome membrane during LC3-associated phagocytosis may be phosphorylated or dephosphorylated, thereby enhancing or inhibiting subsequent phagosome maturation, respectively. These findings have increased our understanding of the SNAP23-associated membrane trafficking mechanism in phagocytes, which has important implications for microbial pathogenesis and innate and adaptive immune responses.
Although there are many reports on the regulation of ion channel expression in transcription and translation, few drugs have been studied to influence post-translational modification of ion channel proteins. The Kv1.5 channel is a potassium ion channel expressed in atrial muscle, belongs to the voltage-gated K+ channel superfamily, and forms an ultrarapid delayed rectifier potassium ion current. It is important to understand the fate of these channel proteins, as cardiac Kv1.5 mutations can cause arrhythmias. Disruption of quantitative and qualitative control mechanisms of channels leads to stagnation and degradation of intracellular channel proteins. As a result, ion channel proteins are not transported to the cell membrane and are involved in the development of atrial fibrillation. This review takes the Kv1.5 channel as an example and focuses on the degradation mechanism of ion channel proteins, and discusses its application to the treatment of arrhythmia by drugs that control the mechanism of ion channel protein degradation.
Background The 5-aminolevulinic acid (ALA)-based photodynamic diagnosis is based on the accumulation of photosensitizing protoporphyrin IX in the tumor after ALA administration. However, the mechanisms connecting exogenous ALA and tumor fluorescence in pancreatic cancer remain unclear. We aimed to elucidate the mechanism underlying the ALA-induced fluorescent.
Methods Human pancreatic duct epithelial cells (hPDECs) and pancreatic cancer cell lines were used. The expressions of ALA-associated enzymes and membrane transporters in these cell lines were investigated. ALA-induced fluorescence was also investigated.
Results The expression of oligopeptide transporter-1 (PEPT-1), through which ALA is absorbed, was significantly higher in AsPC-1 cells and lower in MIA PaCa-2 cells than in hPDECs. AsPC-1 cells showed rapid and intense fluorescence after ALA administration, and that was attenuated by PEPT-1 inhibition. ALA-induced fluorescence was not sufficiently strong in MIA PaCa-2 cells to distinguish the cells from hPDECs.
Conclusion We revealed the association of PEPT-1 with ALA-induced fluorescence. Cancers expressing PEPT-1 could be easily distinguished by this technique from normal cells. These findings help develop novel diagnostic modalities for pancreatic cancer.
Background The Japanese Antarctic Research Expedition (JARE) has been conducting research activities in inland Antarctica, which is extremely cold dryland covered with a thick ice sheet. This environment may cause a health disorder called acute mountain sickness (AMS). To improve the safety of expedition members, we evaluated the impact of extreme environmental conditions on human health and the effectiveness of monitoring of hypoxia for the early detection of AMS.
Methods In total, 9 members from JARE 59 were studied. Dome Fuji Station (Dome F), located 3,810 m above sea level (ASL), was the destination of the research party. We analyzed daily AMS scores (higher values correspond to more severe AMS-related symptoms), physiological findings, and percutaneous arterial blood oxygen saturation (SpO2) during the inland activity. We also determined the factors related to AMS scores.
Results The average AMS score on arrival at Dome F was significantly higher than that at the departure point (560 m ASL). The average SpO2 level was significantly lower than that at other points. The SpO2 level correlated negatively with the AMS score in Spearman’s rank correlation. Generalized estimating equations analysis showed that the AMS score was negatively associated with SpO2 level and positively associated with age.
Conclusion Hypoxia is a contributory factor to AMS which we can easily assess by measuring the SpO2 level with a pulse oximeter. SpO2 monitoring is a potentially useful health management tool for members in inland Antarctic expeditions. In addition, our results are helpful for understanding physiological responses and health issues in extreme environments.
Background The objective of this study was to identify the eating behaviors of patients from 3 months onwards after esophageal surgery. The study was conducted on patients who had been on an oral diet for more than 3 months after the surgery.
Methods Data were collected through interviews and analyzed by a qualitative inductive method based on the Grounded Theory Approach.
Results The results of the analysis revealed that postoperative esophageal cancer patients go through the following three stages in respect of their eating behavior during the first year after surgery: i) Get used to swallowing, ii) Learning how to cope with the symptoms occurring during eating, by failing and succeeding repeatedly, and iii) building self-management skills in terms of eating behaviors. These were identified as the process through which the patients develop their eating behaviors during the first year after surgery.
Conclusion The patients first faced the reality of the underlying issue, namely, difficulty in eating after the surgery, with the feeling that they experienced during swallowing in the process of eating. However, they had no choice but to accept the reality and make efforts to devise practical eating behaviors through experience. Then, eventually, they learned that self-management is necessary not only for maintaining a stable eating behavior, but also for sustaining their lives. In the long-term post-operative patient’s acquisition of new eating habits, medical staff look back and share their experiences so that they can recognize their altered body without being discouraged. However, it is necessary to continue to support them even after they discharge from the hospital by accepting difficulties in eating behavior.
Background Oral mucositis (OM) is a side effect of chemotherapy in head and neck cancer. Severe OM often has a large impact on quality of life. Therefore, the treatment of OM during chemotherapy is very important. It was recently reported that Hangeshashinto (TJ-14), a Japanese traditional medicine (Kampo), is effective for OM caused by fluorinated pyrimidine-based agents used in colon cancer. We investigated the efficacy of TJ-14 for OM.
Methods We enrolled patients with head and neck cancer who were treated with induction chemotherapy between September 2014 and March 2016. In this double-blind trial, patients were randomly assigned to the TJ-14 group or placebo group. Patients were instructed to dissolve 2.5 g of TJ-14 or placebo in 100 ml of drinking water, rinse their mouths with the solution for 30 s and then spit it out. They were not allowed to eat anything for 30 minutes before or after using the mouthwash.
Results The incidence of ≥ grade 2 OM was 37.5% (three patients) in the TJ-14 group and 50.0% (four patients) in the placebo group, with no significant difference between the two groups. The mean day of onset was 9.7 in the TJ-14 group and 6.7 in the placebo group. The mean duration of ≥ grade 2 OM was 1.3 days in the TJ-14 group and 3.7 days in the placebo group. Thus TJ-14 significantly reduced the duration of ≥ grade 2 OM.
Conclusion Treatment of OM with TJ-14 was associated with a statistically significant reduction in the duration of ≥ grade 2 OM compared to placebo. Gargling with TJ-14 is a safe and effective method of administering the drug to patients with head and neck cancer.
Background Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease related to metabolic syndrome, which can progress to liver cirrhosis. Standard medication has not been established. Pemafibrate is a selective peroxisome proliferator-activated receptor (PPAR) α modulator. We retrospectively evaluated the efficacy of pemafibrate in patients with NAFLD.
Methods We retrospectively enrolled 17 patients (ten men, seven women; median age, 63 years; range, 27–81 years). They were all proven to have fatty liver through imaging and had little or no history of drinking (ethanol consumption of < 20 g/day for women and < 30 g/day for men). They were administered pemafibrate from October 2018 to June 2020.
Results After administration, serum triglyceride (TG) tended to be decreased (300.5 ± 22.5 to 239.5 ± 34.3 mg/dL, P = 0.06). Serum high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol levels did not change. ALT was significantly decreased (–47.4%) for six months (57.5 ± 8.8 to 30.3 ± 5.8 U/L, P < 0.01). The values of serum GGT significantly decreased (–48.7%) for sixth months (63.9 ± 10.3 to 32.8 ± 6.6 U/L, P < 0.01). Aspartate aminotransferase (AST) to platelet ratio (APRI), a fibrosis marker, also was significantly decreased in the sixth month (0.7 ± 0.1 to 0.4 ± 0.1, P < 0.05). Body mass index (BMI) and hemoglobin A1c (HbA1c) showed no significant change.
Conclusion Pemafibrate dramatically ameliorated the values of liver function tests and APRI in patients with NAFLD.
Background The present study evaluates the effects of a classroom-based universal program for stress management among elementary school students.
Methods The participating children (aged 11–12 years) were assigned to either an intervention (n = 172) or a control group (n = 100). The program involved one 45-minute session during school hours. The program taught students about cognitive distortions and trained them using cognitive reconstruction. Cognitive distortions were characterized so that children could easily understand them. Students were asked to complete the Children’s Stress Response Test, comprised of five questions about self-efficacy about cognitive reconstruction before and after the program, to assess the program’s effects.
Results The results as observed in the intervention group were as follows: (a) stress responses decreased, (b) self-efficacy in the awareness about one’s feelings and thinking improved, (c) understanding how thinking affects feelings was prompted, (d) self-efficacy to review one’s thinking improved when they felt uncomfortable, and (e) self-efficacy to change one’s negative thinking to adaptive thinking improved.
Conclusion These results suggest that the program was useful for reducing stress responses and improving self-efficacy in cognitive reconstruction among children.
Background Constipation is a common problem in pregnancy. This study aims to elucidate the efficacy of using a bidet before defecation to reduce the severity of constipation and improve the quality of life in pregnancy.
Methods The sample consisted of an experimental group (n = 30) and a control group (n = 30), a total of 60 pregnant women. Randomization was performed using the pitch-and-toss method from simple probability randomization methods. The research data were collected using the Personal Information Form, the Constipation Assessment Scale for Pregnancy, and the Constipation Quality of Life Scale.
Results There was a statistically significant difference between the pregnant women’s mean scores on the Constipation Assessment Scale for Pregnancy due to the intervention of bidet before defecation. Although the members of the intervention group had severe constipation at first, they reported only “some problems” on defecation after the intervention. In addition, statistically significant improvements were observed in the intervention group via all subscales of the Constipation Quality of Life Scale except the satisfaction subscale.
Conclusion Providing pregnant women with training on constipation and information about how to control constipation using a bidet is very important in terms of reducing the severity of constipation, enabling them to feel better and continue their daily activities, and thus to improve their quality of life.
Background Oxytocin is widely used in perinatal medicine, but it can cause serious side effects. Health professionals should be familiar with the pharmacokinetics, dosing regimen, and fetal effects of oxytocin. This study aims to explore the use of oxytocin by healthcare professionals during labor.
Methods This study was conducted in one medical faculty, one training and research hospital, one maternity hospital, and one private hospital in Adana, Turkey. The sample group included 107 participants. The data were gathered using a survey prepared in line with the literature. The survey was comprised of 30 questions. These questions concern the social demographic information of the participants, the knowledge and actual oxytocin use, and the views of the participants. The data were analyzed using descriptive statistics.
Results The average age of the participants was 36.76 ± 8.70 years, the mean of working experience in the delivery room was 7.79 ± 7.73 years. 85.6% of the participants who answered the question of possible effects of oxytocin as contraction, 57.9% of the possible side effects as fetal distress. 69.2% of the participants stated that they applied oxytocin after dilution in a fluid while 47% stated that they applied it after dilution in fluid with 5% Dextrose. While 40% of the participants responded that they sometimes forgot to administer medication, 39.2% stated that they did not register medication in their survey responses.
Conclusion It was determined that most of the participants answered the questions about the effect of oxytocin correctly, but they could not respond to all the side effects of oxytocin. It was found that most of the participants could not answer the storage conditions that are important for the effectiveness of the drug correctly. In addition, the importance level given to the principles of drug administration by the participants was generally found to be high.
Herein, we report a case of atypical spindle cell lipomatous tumor (ASCLT) on both sides of the tongue in a 74-year-old male patient. The patient was referred to our department for treatment of the masses in the tongue. Several elastic soft indolent masses were detected during the first examination. The masses were well defined, and their consistency was similar to that of adipose tissues. No signs of induration were observed in the surrounding tissues. The patient was not aware of the masses, which were only detected during his visit at the dental clinic that referred him to our institution. Thus, the onset of the masses remains unknown. ASCLT was identified via histopathological examination. Then, tumor excision was performed under general anesthesia. Thirteen months after surgery, the condition of the patient was good, and signs of local recurrence or postoperative metastasis were not observed.
We report a case of GCTB in an 84-year-old Japanese man who had a tumor in his left iliac bone and was treated safely with denosumab. The patient noticed a painful mass, with gradual enlargement, in his left low back next to the iliac region. Magnetic resonance imaging revealed that the tumor measured 94 × 66 × 90 mm and was located in the left iliac bone. Histologically, the tumor was composed of proliferative oval-shaped mononuclear cells, admixed with large number of osteoclast-like giant cells. Immunohistochemically, a strong positivity for histone 3.3 G34W mutant protein was observed in the nuclei of the mononuclear cells, confirming the diagnosis of GCTB. Because it was considered as unresectable tumor, the patient was treated with denosumab without any side effects.
This is the first study to examine the long-term effect of 5-aminolevulinic acid mainly on serum lipoproteins in dogs with hyperlipidemia. We studied 5 Miniature Schnauzer cases whose fasting serum total triglyceride and very-low-density lipoprotein of triglyceride levels were extremely high (635 ± 116 and 520 ± 92 mg/dL, respectively). Although the total cholesterol values were normal, the very-low-density lipoprotein of cholesterol level was high (49 ± 7 mg/dL). Each dog received a 5-aminolevulinic acid supplement (5 mg/day) orally for 6 months. The mean values of total triglyceride, very-low-density lipoprotein of both triglyceride and cholesterol decreased significantly after the treatment period (319 ± 29, 245 ± 18, and 27 ± 2 mg/dL, respectively, P < 0.05). Our present results may present evidence that 5-ALA administration contributes to improvement of hyperlipidemia in Miniature Schnauzer.