The abdominal muscles play a role in trunk balance. Abdominal muscle thickness is asymmetrical in stroke survivors, who also have decreased respiratory muscle function. We compared the thickness of the abdominal muscles between the affected and less affected sides in stroke survivors. In addition, the relationship between respiratory muscle function and trunk balance was evaluated. Chronic stroke patients (18 men, 15 women; mean age, 58.94 ± 12.30 years; Mini-Mental Status Examination score ≥ 24) who could sit without assist were enrolled. Abdominal muscle thickness during rest and contraction was measured with ultrasonography, and the thickening ratio was calculated. Respiratory muscle function assessment included maximum respiratory pressure, peak flow, and air volume. Trunk function was evaluated using the Trunk Impairment Scale, and trunk balance was estimated based on the center of pressure velocity and path length within the limit of stability in sitting posture. Abdominal muscles were significantly thinner on the affected side, and the thickening ratio was lower in the affected side (P < 0.05). In addition, the higher thickening ratio of the affected side showed significant relationship with higher trunk function. Moreover, higher respiratory muscle function was significantly correlated with higher level of trunk function and balance in stroke patients (P < 0.05). Thus, chronic stroke survivors have decreased abdominal muscle thickness on the affected side, and respiratory muscle function has positive correlation with trunk function and balance. We propose that respiratory muscle training should be included as part of trunk balance training in chronic stroke patients.

Hepatocellular carcinoma (HCC) remains a major health problem for delayed diagnosis, inefficient surveillance and poor prognosis. Recent studies have indicated that non-coding RNAs contribute to the development of new strategies for diagnosis and treatment of HCC. In the present study, we employed 18 pairs of HCC and matched non-tumor tissues for the identification of differentially expressed microRNAs (miRNAs) in HCC, among which 7 paired specimens were selected randomly for microarray detection. Totally, twenty-three miRNAs were screened out to have statistically significant differences with the threshold of P < 0.01 and fold-change ≥ 2.0 or ≤ 0.5 using miRNA microarray. In the validation stage, two miRNAs exhibited higher expression levels in the HCC tissues compared with those in the matched non-tumor tissues, whereas the expression levels of ten miRNAs were lower in the HCC tissues than those in the matched non-tumor tissues. In further analysis, eight miRNAs, including miR-4270, miR-125b-5p, miR-199a-3p, miR-10a-5p, miR-424-5p, miR-195-5p, miR-106b-5p and miR-3651, were retained, when another constraint about the signal intensity of microarray probes was established. Among these miRNAs, our study was the first to show the higher expression level of miR-3651 and the lower expression level of miR-4270 in HCC. The areas under the receiver-operating-characteristic curve values of miR-3651 and miR-4270 were 0.730 and 0.967, respectively, indicating their potential diagnostic values. Our results may help provide the context for expanded interpretations of miRNA studies involved in the progression of liver disease, potentially serving as a diagnostic tool of HCC.

Pheochromocytomas and paragangliomas are neuroendocrine tumors which arise from adrenal medulla, and sympathetic or parasympathetic nerves, respectively. Hereditary cases afflicted by both or either pheochromocytomas and paragangliomas have been reported: these are called hereditary pheochromocytoma/paraganglioma syndromes (HPPS). Many cases of HPPS are caused by mutations of one of the succinate dehydrogenase (SDH) genes; mainly SDHB and SDHD that encode subunits for the mitochondrial respiratory chain complex II. In this study, we investigated mutations of SDH genes in six HPPS patients from four Japanese pedigrees using peripheral blood lymphocytes (from one patient with pheochromocytoma and five patients with neck paraganglioma) and tumor tissues (from two patients with paraganglioma). Results showed that all of these pedigrees harbor germline mutations in one of the SDH genes. In two pedigrees, a novel IVS2-2A>C mutation in SDHB, at the acceptor-site in intron 2, was found, and the tumor RNA of the patient clearly showed frameshift caused by exon skipping. Each of the remaining two pedigrees harbors a reported missense mutation, R242H in SDHB or G106D in SDHD. Importantly, all these mutations are heterozygous in constitutional DNAs, and two-hit mutations were evident in tumor DNAs. We thus conclude that the newly identified IVS2-2A>C mutation in SDHB is responsible for HPPS. The novel mutation revealed by our study may contribute to improvement of clinical management for patients with HPPS.

Idiopathic pulmonary fibrosis (IPF) is a progressive and incurable disease with limited overall survival. Nintedanib is a multikinase inhibitor, and its efficacy on IPF was demonstrated in phase III trials. However, a discrepancy exists between forced vital capacity (FVC) and patient-reported outcomes during nintedanib treatment. Accordingly, we retrospectively analyzed the effects of nintedanib on FVC and patient-reported outcomes among 25 IPF patients. Patient-reported outcomes were evaluated with modified medical research council (mMRC) grade and COPD assessment test (CAT) score. The changes in mMRC grade, CAT score, and FVC data were obtained 6 months before, at the time of, and 6 and 12 months after nintedanib introduction. Significant difference in the mMRC grade was observed only between the baseline and 6 months after treatment (improvement: p = 0.0429). By contrast, there were significant deterioration (p < 0.001) in the CAT scores between 6 months before and the baseline and significant improvement (p < 0.001) between the baseline and 6 months or 12 months after treatment. Overall, 14 patients were judged as efficient with CAT scores after 6-month treatment. Among these 14 patients, only 4 patients (28.6%) were also judged as efficient with mMRC grade. Thus, the CAT score could be more useful in the subjective assessment of IPF. Moreover, FVC was improved 6 months after nintedanib introduction in 12 out of 24 patients with the complete set of the relevant data. These results indicate that nintedanib exhibits favorable effects in IPF from both subjective and objective evaluations.

PTEN-induced putative kinase protein 1 (PINK1) is a serine/threonine-protein kinase that phosphorylates mitochondrial proteins and is involved in mitophagy. Thus, PINK1 may protect cancer cells against mitochondrial dysfunction during cellular stress. However, the role of PINK1 in lung cancer was rarely explored. In this study, we immunohistochemically analyzed the expression of PINK1 in 256 patients with non-small-cell lung cancer, consisting of 137 patients with adenocarcinoma (AC) and 119 patients with squamous cell carcinoma (SCC). In particular, we focused on the difference in diagnostic or prognostic value of PINK1 expression between AC patients and SCC patients. The patients with AC or SCC were divided into high or low PINK1 expression group, according to the immunohistochemical score that was based on the percentage of PINK1 positive cells and staining intensity. Among the 137 AC specimens, 52 specimens (37.96%) were judged as high PINK1 expression, and likewise, among 119 SCC specimens, 42 specimens (35.29%) were judged as high PINK1 expression. Importantly, high PINK1 expression was significantly associated with postoperative chemoresistance of AC, but not in case of SCC. Moreover, high PINK1 expression was identified as a poor prognostic factor for AC, but not for SCC. These results may reflect the biological difference between AC and SCC. In conclusion, high PINK1 expression is correlated with poor response to chemotherapy and is an independent prognostic factor for AC, but not for SCC. Our findings suggest that PINK1 detection could help stratify patients who may have poor response to chemotherapy and guide the individual treatment.

The combinations of oral fluoropyrimidines and cisplatin such as capecitabine and cisplatin (XP) or S-1 and cisplatin (SP) are regarded as a standard therapy against unresectable, recurrent, or advanced gastric cancer (AGC). Especially, SP is the most common regimen against AGC in Japan. For patients with human epidermal growth factor receptor type 2 (HER2)-positive AGC, trastuzumab, a monoclonal antibody targeting HER2 antibody, is additionally used in combination. Although trastuzumab in combination with XP (trastuzumab-XP) have been widely accepted, the efficacy of trastuzumab in combination with SP (trastuzumab-SP) lacks sufficient verification. The aim of the present study is to validate the comparability of trastuzumab-SP to trastuzumab-XP. Patients with HER2-positive AGC were assigned to the trastuzumab-XP or trastuzumab-SP group. We then retrospectively compared the efficacy and safety between both groups. As a first-line chemotherapy, trastuzumab in combination with XP or SP was administered to 58 patients: 28 with trastuzumab-XP and 30 with trastuzumab-SP. In the trastuzumab-XP group, response rate (RR), disease control rate (DCR), median progression-free survival (mPFS), and median overall survival (mOS) were 39.3%, 89.3%, 7.9 months, and 20.0 months, respectively. In the trastuzumab-SP group, RR, DCR, mPFS and mOS were 50.0%, 86.7%, 6.9 months, and 16.7 months, respectively. No significant difference in efficacy was observed between both groups. Severe hand-foot syndrome was observed more frequently in the trastuzumab-XP group than in the trastuzumab-SP group (14.3% vs. 0%, p = 0.05). Trastuzumab in combination with SP is a potential first-line therapeutic option for patients with HER2-positive AGC.

Pattern recognition receptors recognize RNA viruses and trigger type I and III interferon (IFN) production and apoptosis to limit viral replication and spread. Some innate immune cells produce oxidants in response to viral infection to protect against invasion. Recent studies have demonstrated the virucidal activity of hypothiocyanous acid (HOSCN), an oxidant generated by the peroxidase-catalyzed reaction of thiocyanate with hydrogen peroxide. However, the effects of HOSCN on host antiviral responses are still unknown. In this study, we aimed to clarify the role of HOSCN in host antiviral responses against RNA viruses in airway epithelial cells using polyinosinic-polycytidylic acid (polyI:C), a mimic of viral RNA. Our results show that HOSCN repressed antiviral responses in NCI-H292 human airway epithelial cells. HOSCN decreased polyI:C-induced apoptosis and the expression levels of IFNB1, IFNL1, IFNL2 and IFNL3 mRNAs. In addition, the induction of other interferon regulatory factor 3 (IRF3)-dependent genes was also suppressed by HOSCN. Further analyses focused on IRF3 revealed that HOSCN inhibited the phosphorylation of IRF3 at Ser386 and Ser396 as well as its dimerization and nuclear translocation by inhibiting the phosphorylation of TANK-binding kinase 1 (TBK1). Furthermore, HOSCN led to the phosphorylation of IRF3 at residues other than Ser386 and Ser396, implying that HOSCN may cause a conformational change in IRF3 to impair its function. Collectively, these results suggest that HOSCN plays a novel signaling role in the antiviral response, acting as a negative regulator of apoptotic and TBK1-IRF3 signaling pathways and limiting IRF3-dependent gene expression.