Decreased Proteasomal Function Exacerbates Endoplasmic Reticulum Stress-Induced Chronic Inflammation in Obese Adipose Tissue.

Low-grade chronic inflammation contributes to both aging and the pathogenesis of age-related diseases. White adipose tissue (WAT) in obese individuals exhibits chronic inflammation, which is associated with obesity-related disorders. Aging exacerbates obesity-related inflammation in WAT; however, the molecular mechanisms underlying chronic inflammation and its exacerbation by aging remain unclear. Age-related decline in activity of the proteasome, a multisubunit proteolytic complex, has been implicated in age-related diseases. This study employed a mouse model with decreased proteasomal function that exhibits age-related phenotypes to investigate the impact of adipocyte senescence on WAT inflammation. Transgenic mice expressing proteasomal subunit ß5t with weak chymotrypsin-like activity experience reduced lifespan and develop age-related phenotypes. Mice fed with a high-fat diet and experiencing proteasomal dysfunction exhibited increased WAT inflammation, increased infiltration of proinflammatory M1-like macrophages, and increased proinflammatory adipocytokine-like monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, and tumor necrosis factor-α, which are all associated with activation of endoplasmic reticulum (ER) stress-related pathways. Impaired proteasomal activity also activated ER stress-related molecules and induced expression of proinflammatory adipocytokines in adipocyte-like cells differentiated from 3T3-L1 cells. Collectively, the results suggesed that impaired proteasomal activity increases ER stress and that subsequent inflammatory pathways play pivotal roles in WAT inflammation. Because proteasomal function declines with age, age-related proteasome impairment may be involved in obesity-related inflammation among elderly individuals.

[Invasive Mucinous Adenocarcinoma that Invades the Wall of a Cystic Lesion:Report of a Case].

Invasive mucinous adenocarcinoma (IMA) is a rare and special type of lung adenocarcinoma. We report a case of IMA presenting as a cystic lesion in the S10 of the right lung, diagnosed by surgical biopsy and treated with right lower lobectomy. The patient was a 60-year-old man who was found to have a 10-mm-sized frosted ground-glass opacity with a 10-mm-sized air space in the S10 of the right lung while undergoing follow-up after renal cancer surgery in 2018. The air space gradually enlarged and, in 2022, began to show a 40-mm-sized cyst, with partial wall thickening and nodularity on the caudal side. A thoracoscopic partial pneumonectomy was performed to confirm the diagnosis of IMA, and a thoracoscopic radical resection of the right remaining lower lobe was performed. It is important to recognize that adenocarcinoma may occur in patients with thin-wall cavity, as in this case. Additionally, it is necessary to determine the treatment strategy based on the assumption that the tumor may extend to the entire cavity wall, even if it is thin-walled.

The risk of weekend biopsy: Impact of specimen source and fixation status on HER2 assessment in the treatment of advanced gastric cancer (The HER_WEEKEND study).

Accurate evaluation of human epidermal growth factor receptor type 2 (HER2) expression is crucial for determining chemotherapy regimens in gastric cancer. However, formalin fixation status has been identified as an important factor affecting HER2 assessment reliability. This retrospective cohort study aimed to investigate the correlation between sample collection day (weekday vs. weekend) and source (biopsy vs. surgical specimens) in assessing HER2 expression in patients with unresectable advanced/recurrent gastric cancer. Data were collected from gastric cancer patients who received chemotherapy at a single public hospital in Japan from 2008 to 2021. The analysis included 177 patients (109 men, 68 women) with a median age of 68.0 (21-88) years, and the primary outcome was the HER2 positivity rate. The overall HER2 positivity rate was 18.1%, with higher rates on weekdays (20.0%) compared to weekends (12.8%). Biopsies had higher positivity rates on weekdays (23.9%) but lower rates on weekends (11.1%) than surgical specimens. Significant differences were observed in formalin fixation times between weekdays and weekends for both biopsies and surgical samples. The study findings suggest that longer formalin fixation times on weekends may lead to underestimating HER2 expression, particularly in biopsies. Therefore, it is crucial to be cautious of excessive formalin fixation when collecting samples, especially during weekend biopsies.

Pulmonary capillary hemangiomatosis-predominant vasculopathy in a patient with rheumatoid arthritis-associated interstitial lung disease: An autopsy report.

Pulmonary capillary hemangiomatosis (PCH) is a rare cause of pulmonary hypertension (PH) associated with poor prognosis. Clinically, it is characterized by severe hypoxemia, centrilobular ground-glass opacities on computed tomography, and pulmonary congestion triggered by pulmonary vasodilating therapy. In some cases, PCH has been reported to develop with other disorders including connective tissue disease; however, to date, no reports have described PCH in a patient with rheumatoid arthritis. We report a case of a 59-year-old male PCH patient with rheumatoid arthritis and associated pulmonary fibrosis. He was initially diagnosed with severe group 3 PH and received sildenafil, which generated a favorable hemodynamic response. However, 5 years later, his pulmonary hemodynamics deteriorated, and he died at the age of 67. An autopsy was performed, and thickening of alveolar septa and capillary proliferation, pathological features of PCH, were extensively observed in both lungs. We discuss when PCH developed, how sildenafil improved his hemodynamics, and how PCH could be clinically detected by noninvasive evaluations.