Supersulphides provide airway protection in viral and chronic lung diseases.

Supersulphides are inorganic and organic sulphides with sulphur catenation with diverse physiological functions. Their synthesis is mainly mediated by mitochondrial cysteinyl-tRNA synthetase (CARS2) that functions as a principal cysteine persulphide synthase (CPERS). Here, we identify protective functions of supersulphides in viral airway infections (influenza and COVID-19), in aged lungs and in chronic lung diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF). We develop a method for breath supersulphur-omics and demonstrate that levels of exhaled supersulphides increase in people with COVID-19 infection and in a hamster model of SARS-CoV-2 infection. Lung damage and subsequent lethality that result from oxidative stress and inflammation in mouse models of COPD, IPF, and ageing were mitigated by endogenous supersulphides production by CARS2/CPERS or exogenous administration of the supersulphide donor glutathione trisulphide. We revealed a protective role of supersulphides in airways with various viral or chronic insults and demonstrated the potential of targeting supersulphides in lung disease.

[Effectiveness of Nivolumab in a Case of Inoperable Advanced Gastric Cancer with Lung Metastasis].

A 66-year-old man was diagnosed with inoperable advanced gastric cancer with liver and peritoneal metastases. The patient underwent SOX therapy as primary chemotherapy; subsequently, liver and peritoneal metastases disappeared. However, lung metastasis was detected later, and weekly paclitaxel(PTX)combined with ramucirumab(RAM)chemotherapy was initiated; subsequently, lung metastasis and advanced gastric cancer disappeared. During remission, lung metastasis was detected again. Although weekly PTX combined with RAM chemotherapy was reinitiated, a progressive disease status was achieved. As tertiary chemotherapy, nivolumab therapy(240 mg/body, every 2 weeks)was initiated for 20 courses over 11 months. This therapy was significantly effective, which aid the patient to achieve a complete response. The patient survived and is healthy for 5 years due to chemotherapy administration alone.

Mesh erosion into the rectum after laparoscopic posterior rectopexy: A case report.

INTRODUCTION: Rectal prolapse typically presents in elderly women with protruding full-thickness rectum from the anus. Rectopexy using mesh is known to be a highly curative treatment for rectal prolapse, however, this procedure carries the risk of severe complication as mesh erosion. PRESENTATION OF CASE: A 78-year-old woman who had undergone laparoscopic posterior rectopexy 4 years earlier visited the outpatient clinic with a complaint of bloody stool. A colonoscopy and computed tomography revealed that part of the mesh had migrated into the rectal lumen at 8 cm from the anal verge. Based on the above findings, a diagnosis of mesh erosion into the rectum was made. Complete removal of the mesh and tacker with rectal resection was performed. Before rectopexy, the patient had severe fecal incontinence, and her anal sphincter function was decreased, therefore, Permanent colostomy was indicated instead of anastomosis. In the resected specimen, the mesh was folded and placed in the mesenteric fat of the posterior wall of the rectum, with the corner of the edge of the mesh protruding into the inside lumen. DISCUSSION: Mesh erosion typically occurs when using mesh made of synthetic mesh and non-absorbable threads; it might induce chronic irritation and friction due to mesh shrinkage. CONCLUSION: To prevent mesh erosion, it is important to pay attention to the mesh materials used and ensure secure fixation.

PGC-1α regulates airway epithelial barrier dysfunction induced by house dust mite.

BACKGROUND: The airway epithelial barrier function is disrupted in the airways of asthmatic patients. Abnormal mitochondrial biogenesis is reportedly involved in the pathogenesis of asthma. However, the role of mitochondrial biogenesis in the airway barrier dysfunction has not been elucidated yet. This study aimed to clarify whether the peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α), a central regulator of mitochondrial biogenesis, is involved in the disruption of the airway barrier function induced by aeroallergens. METHODS: BEAS-2B cells were exposed to house dust mite (HDM) and the expressions of PGC-1α and E-cadherin, a junctional protein, were examined by immunoblotting. The effect of SRT1720, a PGC-1α activator, was investigated by immunoblotting, immunocytochemistry, and measuring the transepithelial electrical resistance (TEER) on the HDM-induced reduction in mitochondrial biogenesis markers and junctional proteins in airway bronchial epithelial cells. Furthermore,the effects of protease activated receptor 2 (PAR2) inhibitor, GB83, Toll-like receptor 4 (TLR4) inhibitor, lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS), protease inhibitors including E64 and 4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) on the HDM-induced barrier dysfunction were investigated. RESULTS: The amounts of PGC-1α and E-cadherin in the HDM-treated cells were significantly decreased compared to the vehicle-treated cells. SRT1720 restored the expressions of PGC-1α and E-cadherin reduced by HDM in BEAS-2B cells. Treatment with SRT1720 also significantly ameliorated the HDM-induced reduction in TEER. In addition, GB83, LPS-RS, E64 and AEBSF prevented the HDM-induced reduction in the expression of PGC1α and E-cadherin. CONCLUSIONS: The current study demonstrated that HDM disrupted the airway barrier function through the PAR2/TLR4/PGC-1α-dependent pathway. The modulation of this pathway could be a new approach for the treatment of asthma.

[A CASE OF BRONCHIAL ASTHMA IN A YOUNGER PATIENT WITH VOCAL CORD DYSFUNCTION].

We present a case of a 17-year-old woman with a history of bronchial asthma since two years of age. She had daily asthma attacks from the age of fourteen, and the addition of oral corticosteroids and omalizumab to regular inhaled corticosteroid inhalation failed to relieve symptoms. She was referred to our hospital for detailed examination. On admission, physical examination was normal, but she had complained of dyspnea at the round. Monophonic wheezes and stridor were heard over the anterior neck, while no rales were audible over any part of the chest. Laryngoscopy revealed paradoxical movement of the vocal cords, and a diagnosis of vocal cord dysfunction (VCD) was made. The apparent severe asthma symptoms were considered to reflect VCD, and the treatment for bronchial asthma was stepped down without any recurrence of asthma attacks. Although the etiology of the VCD was unknown, VCD is more common in young women, so stress and personality factors are thought to be involved. It has been noted that childhood asthma often improves between childhood and adolescence, but refractory cases have been noted. In intractable bronchial asthma cases, it is necessary to consider the complications of other diseases, such as VCD, and to perform appropriate management.

Nitrosative stress in patients with asthma-chronic obstructive pulmonary disease overlap.

BACKGROUND: Asthma-chronic obstructive pulmonary disease overlap (ACO) has frequent exacerbations and a poor quality of life and prognosis compared with those of chronic obstructive pulmonary disease alone. However, the pathogenesis of ACO has not been fully elucidated yet. OBJECTIVES: The aim of this study was to investigate nitrosative stress, which causes a redox imbalance and tissue inflammation in the airways of patients with ACO, and to evaluate the relationship between nitrosative stress and the clinical course in study subjects. METHODS: Thirty healthy subjects and 56 asthmatic patients participated in this study. The asthmatic patients were divided into 33 asthmatic patients and 23 patients with ACO. The study subjects had been followed prospectively for 2 years to evaluate the clinical course. Nitrosative stress was evaluated based on the production of 3-nitrotyrosine (3-NT) in sputum cells. RESULTS: Production of 3-NT was significantly enhanced in patients with ACO compared with that in asthmatic patients. Amounts of reactive persulfides and polysulfides, newly identified powerful antioxidants, were significantly decreased in the ACO group. Baseline levels of 3-NT were significantly correlated with the frequency of exacerbations and decrease in FEV1 adjusted by age, smoking history, and blood eosinophil count. The 3-NT-positive cells were also significantly correlated with amounts of proinflammatory chemokines and cytokines. CONCLUSIONS: These findings suggested that greater nitrosative stress occurred in the airways of patients with ACO, and the degree of nitrosative stress was correlated with an impairment in the clinical course. Nitrosative stress might be related to the pathogenesis of ACO.

Physical inactivity is associated with decreased growth differentiation factor 11 in chronic obstructive pulmonary disease.

BACKGROUND: Growth differentiation factor 11 (GDF11) is reported to possess anti-aging and rejuvenating effects, including muscle regeneration and to be highly expressed in skeletal muscle. Recently, we demonstrated that the levels of plasma GDF11 were decreased in COPD. However, the effect of decreased circulating GDF11 in the pathophysiology of COPD remains unknown. The aim of this study is to investigate the association between the plasma GDF11 levels and various clinical parameters in patients with COPD. PATIENTS AND METHODS: Eighteen ex-smokers as control subjects and 70 COPD patients participated in the current study. We measured the levels of plasma GDF11 using immunoblotting, lung function, physical activity using a triaxial accelerometer, quadriceps strength, exercise capacity, and systemic inflammatory markers. We investigated the association between the levels of plasma GDF11 and these clinical parameters. RESULTS: The levels of plasma GDF11 in the COPD patients had significant positive correlations with the data of lung function. Furthermore, the levels of plasma GDF11 were significantly correlated with the physical activity, quadriceps strength, and exercise capacity. Moreover, the levels of plasma GDF11 were significantly correlated with the data of inflammatory markers. Although various factors were related to GDF11, the multiple regression analysis showed that physical activity was significantly associated with the levels of plasma GDF11. CONCLUSION: Physical inactivity was significantly related to the decreased GDF11 levels in COPD, which might be useful for understanding the pathogenesis of COPD. Clarifying the relationships between the physical inactivity and GDF11 may reveal a potentially attractive therapeutic approach in COPD via increasing the plasma levels of GDF11.