Cytotoxic effects of radiation play an important role in the treatment of head and neck cancer. However, irradiation is known to lead to the migration of various cancer cells, including those of head ...and neck cancer. Recently, fibroblasts in the cancer microenvironment have been reported to be involved in this mechanism. Nevertheless, the mechanism underlying migration of head and neck cancer cells remains unclear. Herein, we aimed to elucidate this migration mechanism induced by irradiation in terms of the interaction of head and neck cancer cells with fibroblasts.
We used the head and neck squamous cell carcinoma (HNSCC) cell lines SAS and FaDu as well as fibroblast cell lines. These cells were irradiated and their viability was compared. In fibroblasts, changes in interleukin-6 (IL-6) secretion caused by irradiation were measured by enzyme-linked immunosorbent assay (ELISA). The cell migration ability of cancer cells was evaluated via a migration assay using a semipermeable membrane. HNSCC cells were cocultured with irradiated and nonirradiated fibroblasts, and their migration ability under each condition was compared. We also examined the effect of IL-6 on the migration of HNSCC cells. Furthermore, to investigate the effect of fibroblast-derived IL-6 on the migration ability of HNSCC cells, we conducted a coculture study using IL-6 neutralizing antibody.
Irradiation reduced the survival of HNSCC cells, whereas fibroblasts were resistant to irradiation. Irradiation also increased IL-6 secretion by fibroblasts. Migration of HNSCC cells was enhanced by coculture with fibroblasts and further enhanced by coculture with irradiated fibroblasts. We also confirmed that the migration of HNSCC cells was induced by IL-6. The enhanced migration of cancer cells caused by coculturing with fibroblasts was canceled by the IL-6 neutralizing antibody.
These results show that fibroblasts survive irradiation and induce the migration ability of HNSCC cells through increased secretion of IL-6.
Influenza infection and associated epidemics represent a serious public health problem. Several preventive and curative measures exist against its spread including vaccination and therapeutic agents ...such as neuraminidase inhibitors (e.g., oseltamivir, zanamivir, as well as peramivir and laninamivir, which are licensed in several countries) and adamantanes (e.g., amantadine and rimantadine). However, neuraminidase inhibitor- and adamantane- resistant viruses have been detected, whereas vaccines exhibit strain-specific effects and are limited in supply. Thus, new approaches are needed to prevent and treat influenza infections. Catechins, a class of polyphenolic flavonoids present in tea leaves, have been reported as potential anti-influenza virus agents based on experimental and clinical studies. (-)-epigallocatechin gallate (EGCG), a major and highly bioactive catechin, is known to inhibit influenza A and B virus infections in Madin-Darby canine kidney cells. Additionally, EGCG and other catechin compounds such as epicatechin gallate and catechin-5-gallate also show neuraminidase inhibitory activities as demonstrated via molecular docking. These catechins can bind differently to neuraminidase and might overcome known drug resistancerelated virus mutations. Furthermore, the antiviral effects of chemically modified catechin derivatives have also been investigated, and future structure-based drug design studies of catechin derivatives might contribute to improvements in influenza prevention and treatment. This review briefly summarizes probable mechanisms underlying the inhibitory effects of tea catechins against influenza infection and their clinical benefits on influenza prevention and treatment. Additionally, the great potential of tea catechins and their chemical derivatives as effective antiviral agents is described.
We aimed to evaluate the efficacy and safety of propranolol gel at various concentrations with infantile hemangiomas after proliferative phases. We designed a single-center, randomized, double-blind, ...dose-dependent trial with placebo control and randomized patients to receive propranolol gel at 0, 1, or 5%, twice daily for 24 weeks. The primary efficacy endpoint was the percentage change in redness of the tumors. Safety endpoints were skin characteristics changes and systemic symptoms. We made two comparisons to evaluate the superiority of 1 and 5% propranolol gels against placebo for primary endpoint analysis and used the t-test to compare parents’ satisfaction with these treatments. Initially, 19 patients were enrolled, but 8 were excluded from the analysis. We were underpowered to answer the question of efficacy. In the per-protocol set, we found similar results for the redness percentage change among the patients on placebo, 1 and 5% gel. However, the difference in redness before and after treatment suggested a slight decreasing trend of lesion’s redness as the propranolol concentration increased. The difference in parents’ satisfaction between the placebo and 5% propranolol gel groups was significant (p = 0.08). We observed no serious adverse events. We did not find an obvious dose-dependent effect for the propranolol gel treatment against infantile hemangiomas after the proliferative phase. However, external applications twice daily were less burdensome for parents and led to good compliances. It had a favorable safety profile in Japanese pediatric patients with infantile hemangiomas.
We performed a systematic review and Bayesian network meta-analysis to determine atypical antipsychotics that are effective and safe for the treatment of psychosis in Parkinson’s disease (PD). We ...conducted a comprehensive literature search using PubMed/MEDLINE, Cochrane Library, and Japana Centra Revuo Medicina (Ichu-shi Web). We used randomized controlled trials evaluating the utility of atypical antipsychotics for the treatment of psychosis in PD using the Brief Psychiatric Rating Scale (BPRS) and the Unified PD rating Scale parts III (UPDRS-III) as the endpoints. Posterior distributions of mean differences between each treatment and placebo were estimated using Bayesian network meta-analysis. The distributions describing each treatment effect were expressed as means (95% credible intervals). Ten trials involving any two treatment arms using clozapine (64 subjects in four trials), olanzapine (99 subjects in three trials), quetiapine (79 subjects in five trials), risperidone (five subjects in one trial), or placebo (156 subjects in seven trials) were finally included in the present study. Pooled estimates of each posterior distribution based on the BPRS were as follows: clozapine, −2.0 (−6.7 to 2.7); olanzapine, 0.5 (−2.3 to 3.4); quetiapine, 0.3 (−3.9 to 4.5); and risperidone, −4.7 (−57.4 to 53.3). Based on the UPDRS-III, the pooled estimates were clozapine, 0.7 (−3.8 to 4.3); olanzapine, 2.8 (0.8 to 5.1); quetiapine, 3.3 (−0.7 to 5.8); and risperidone, 4.5 (−57.7 to 63.4). Although clozapine had an effective and relatively safe profile, all atypical antipsychotics included in the present study may be unsafe, as they may worsen motor function when compared to placebo.
The etiology of autism spectrum disorder (ASD) remains unclear; however, the toxic environmental exposure to oxidative stress has been suggested to play an important role in its pathogenesis. A loss ...of balance between oxidative stress and antioxidant capacity produces an excess of reactive nitrogen species (RNS) such as nitric oxide (NO). Polyunsaturated fatty acids (PUFAs), particularly arachidonic acid, docosahexaenoic acid and eicosapentaenoic acid, are closely related to NO and NO synthase. In the pathophysiology of ASD, NO is related to the activity of primary PUFAs. NO modulates short- and long-term synaptic plasticity and plays essential roles in the regulation of a wide range of physiological processes including neurotransmission. NO affects the function of reactive oxygen species (ROS) in the local cellular milieu, in which biological antioxidants are present. NO plays a double role in the organism showing both neuroprotective and neurotoxic effects. Redox imbalance leads to the activation of the neurotoxic pathway, suggesting crossroads for the neurotoxic or neuroprotective effects of NO. Furthermore, the dual role of NO could depend on the adaptive functions of the antioxidant capacity and oxidative stress-related ROS/RNS as the disease progresses. Increased concentrations of arachidonic acid promote neuronal survival, and the dysregulation of the NO system plays an important role in the pathophysiology of bipolar disorder and recurrent depressive disorders. Therefore, the NO system could provide useful drug targets for these diseases. NO and NO donors also show therapeutic potential for Alzheimer's disease and schizophrenia with refractory symptoms and cognitive dysfunction.
Homicide followed by suicide (HS) is a tragic event with varied characteristics across countries and regions. Compared to Western countries, there are limited studies on HS in Asian countries. ...Therefore, this study aimed to clarify the characteristics of recent HS cases by examining forensic autopsy records from 2008 to 2020 collected from the Department of Legal Medicine, Chiba University, in Japan. A total of 77 HS cases were identified, involving 77 perpetrators (52 completed suicides, 25 attempted suicides), with 28 perpetrator and 89 victim autopsies. Our findings showed that older adults accounted for nearly half of the victims; victims were mostly females, whereas most perpetrators were male. The most common HS relationship was that between a parent and a child. Autopsy findings showed that the most common cause of death was strangulation, and illegal drugs were detected only in a few cases; however, psychotropic drugs were detected in child victims. No obvious evidence of past child physical abuse by caregivers was found. In contrast, intimate partner violence (IPV) was present, with a history of IPV found in half of HS cases involving adult intimate partner relationships. Notably, gender differences in age and relationship to the victim were identified. Likewise, some perpetrators may have expressed their plans and intentions for HS before the event, which may represent an important sign for HS prevention. However, to accurately reveal the course of HS, nationwide integrated statistics, forensic autopsies, including toxicological analyses of the deceased; and forensic psychiatric perspectives, including psychological autopsy, are required.
Purpose
Recent studies have revealed the impact of spinopelvic factors on the risk of dislocation after total hip arthroplasty (THA). This study examined the risk factors of impingement that can lead ...to dislocation using pre- and postoperative spinopelvic radiographs.
Methods
We studied 143 consecutive patients with end-stage hip osteoarthritis who were eligible for THA at our institute. Pre-operative pelvic incidence (PI), sacral slope (SS), lumbar lordosis (LL), sagittal vertical axis (SVA) in the standing and sitting position, and centre-edge angle (CE) were measured. The post-operative SS, LL, SVA, femoral shaft angle, and radiographic alignment of the acetabular component were also measured. We performed a multiple linear regression analysis to determine the risk factors for anterior and posterior impingement using pre-operative demographic and radiographic parameters. The clearance of anterior and posterior implant impingement was used for the surrogate-dependent variable for dislocation.
Results
A total of 95 patients were included in the analysis. There were significant differences in SS, LL, and SVA between the standing and sitting positions (
P
< 0.001). A multiple linear regression analysis showed that the PI–LL, LL changes, and CE were associated with the posterior impingement (
β
= − 0.21, 0.24, and −0.27, respectively). Moreover, PI–LL was also associated with the anterior impingement in the sitting position (
β
= − 0.27).
Conclusion
Our results suggest that a flatback with a rigid spine leads to posterior impingement, and a well-balanced spine leads to anterior impingement, which can be a potential risk factor for dislocation.
Stereoselective halogenation is a highly useful organic transformation for multistep syntheses because the resulting chiral organohalides can serve as precursors for various medicinally relevant ...derivatives. Even though decarboxylative halogenation of aliphatic carboxylic acids is a useful and fundamental synthetic method for the preparation of a variety of organohalides, an enantioselective version of this reaction has not been reported. Here we report a highly enantioselective decarboxylative chlorination of β-ketocarboxylic acids to obtain α-chloroketones under mild organocatalytic conditions. The present method is also applicable for the enantioselective synthesis of tertiary α-chloroketones. The conversions of the resulting α-chloroketones into α-aminoketones and α-thio-substituted ketones via S
2 reactions at the tertiary carbon centres are also demonstrated. These results constitute an efficient approach for the synthesis of chiral organohalides and are expected to enhance the availability of enantiomerically enriched chiral compounds with heteroatom-substituted chiral stereogenic centres.
ABSTRACTThe selection of the sowing date is one of the most important decisions in soybean production. It is important for farmers to know the expected seed yield when developing a sowing plan. The ...objective of this study was to quantitatively reveal the decreased seed yield ratio during late sowing in southwestern Japan under irrigated conditions. Total above ground dry matter and distribution were measured from July to August sowing in 2018 and 2019 in Fukuyama, Hiroshima, Japan. The harvest index in the August sowing did not decrease compared to the July sowing under irrigated conditions. The decrease in yield was related to the total aboveground dry matter rather than to the harvest index. The decrease in total aboveground dry matter was related to the total amount of solar radiation intercepted rather than to radiation use efficiency. A significant regression equation was obtained for the relative yield, which was calculated from the maximum seed yield observed from early to mid-July. When seeds were sown after mid-July, our result showed that the seed yield will decrease by 0.60% per day for Sachiyutaka A1 and by 0.64% for Akimaro, even under conditions of 100% seedling establishment and controlled soil water conditions. This regression equation can be used in fields as an indicator of seed yield where irrigation is possible.
Although several studies have evaluated the efficacy of thiazolidinediones (TZD) for the treatment of Alzheimer’s disease (AD), investigation of the impact of apolipoprotein E (ApoE) gene ...polymorphisms on the efficacy of TZD remains insufficient. We investigated the impact by conducting a systematic review and meta-analysis. MEDLINE, Cochrane Library, and Japana Centra Revuo Medicina were searched to identify relevant studies based on eligibility criteria. Mean differences (MD) of Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-Cog) total score with 95% confidence intervals (CI) were calculated for subgroups stratified by ApoE genotype. To evaluate the impact of ApoE gene polymorphisms, meta-regression analysis was also conducted to calculate the regression coefficient (Coef) of ApoE expression status with 95% CI. Three randomized controlled studies comparing rosiglitazone and placebo, with a total of 2381 subjects met the eligibility criteria. ApoE expression status was reported in 983 individuals (ApoE4-positive, 141; ApoE4-negative, 842). When compared to placebo, rosiglitazone significantly decreased ADAS-Cog score in ApoE4-negative individuals (MD, −1.37; 95% CI, −2.09 to −0.65), but significantly increased ADAS-Cog score in ApoE4-positive individuals (MD, 2.18; 95% CI, 0.52 to 3.85). The meta-regression analysis showed a significant association between efficacy and ApoE expression status (Coef, 3.55; 95% CI, 1.42 to 5.68). Although the present results should be interpreted with caution because of the limited number of studies, our findings suggest that ApoE gene polymorphisms impact the efficacy of rosiglitazone for AD patients. This finding would provide useful information for the development of new agents for AD.
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