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Pulmonary manifestations of benign metastasizing leiomyoma (BML) usually include multiple well-defined, round, bilateral nodules. Low-grade endometrial stromal sarcoma (LG-ESS) is a rare uterine tumor. A 70-year-old woman visited the clinic complaining of acute cough and dyspnea in April 2017. Chest computed tomography (CT) revealed pneumothorax and multiple pulmonary nodules. She had a history of hysterectomy for uterine leiomyoma 23 years ago. Biopsy revealed that the pulmonary masses were consistent with BML. However, the patient had two subsequent episodes of acute, recurrent respiratory distress, accompanied by massive pleural effusions and hydropneumothorax over the next two years. A chest CT performed for acute dyspnea revealed large and multiple hydropneumothoraces. The size and distribution of pulmonary masses were aggravated along with cystic changes and bilateral pleural effusions. Given this aggressive feature, additional immunohistochemical findings and gynecologic pathologist review confirmed the correct diagnosis to be LG-ESS. After initiating anti-estrogen therapy, the patient achieved a partial response, without recurrence of symptoms, for 28 months. Metastatic LG-ESS responds well to anti-hormonal therapy. If the clinical pattern of a disease is different than expected, the possibility of a correction in the diagnosis should be considered.

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common neurodegenerative diseases. Many studies have demonstrated that the release of NLRP3 inflammasome-mediated proinflammatory cytokines by the excessive activation of microglia is associated with the pathogenesis of AD and PD and suggested that the NLRP3 inflammasome plays an important role in AD and PD development. In both diseases, various stimuli, such as Aβ and α-synuclein, accelerate the formation of the NLRP3 inflammasome in microglia and induce pyroptosis through the expression of interleukin (IL)-1β, caspase-1, etc., where neuroinflammation contributes to gradual progression and deterioration. However, despite intensive research, the exact function and regulation of the NLRP3 inflammasome has not yet been clearly identified. Moreover, there have not yet been any experiments of clinical use, although many studies have recently been conducted to improve treatment of inflammatory diseases using various inhibitors for NLRP3 inflammasome pathways. However, recent studies have reported that various natural products show improvement effects in the in vivo models of AD and PD through the regulation of NLRP3 inflammasome assembly. Therefore, the present review provides an overview of natural extraction studies aimed at the prevention or treatment of NLRP3 inflammasome-mediated neurological disorders. It is suggested that the discovery and development of these various natural products could be a potential strategy for NLRP3 inflammasome-mediated AD and PD treatment.

Renal cell carcinoma (RCC) represents the most common form of kidney cancer, which accounts for 3–5% newly diagnosed cancer cases. Since limited therapies are available for RCC, a search for new options is required. Therefore, in this study, we evaluated the combination effect of cinnamaldehyde (CNM) and hyperthermia treatment. CNM treatment combined with 43 °C hyperthermia synergistically increased cytotoxicity in RCC cell line ACHN cells. Through Western blot assays, we observed increased apoptosis signaling and decreased proliferation/metastasis signaling, along with a repressed heat shock protein 70 level. In flow cytometry analyses, CNM and hyperthermia combination clearly induced apoptosis and mitochondrial potential of ACHN cells, while arresting the cell cycle. Investigation of reactive oxygen species (ROS) suggested a significant increase of ROS generation by CNM and 43 °C hyperthermia co-treatment. We could verify that ROS is crucial in the apoptotic action of combination treatment with CNM and hyperthermia through further experiments regarding an ROS scavenger. Overall, we suggest CNM and hyperthermia combination treatment as an alternative option of anticancer strategies for RCC.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known to behave as an attractive anti-cancer agent in various cancers. Despite its promise TRAIL has limitations such as short half-life and rapid development of resistance. In this regard, approaches to sensitizers of TRAIL that can overcome the limitations of TRAIL are necessary. However, the molecular targets and mechanisms underlying sensitization to TRAIL-induced apoptosis are not fully understood. Here, we propose that reactive oxygen species modulator-1 (Romo1) as an attractive sensitizer of TRAIL. Romo1 is a mitochondrial inner membrane channel protein that controls reactive oxygen species (ROS) production, and its expression is highly upregulated in various cancers, including colorectal cancer. In the present study, we demonstrated that Romo1 inhibition significantly increased TRAIL-induced apoptosis of colorectal cancer cells, but not of normal colon cells. The combined effect of TRAIL and Romo1 inhibition was correlated with the activation of mitochondrial apoptosis pathways. Romo1 silencing elevated the protein levels of BCL-2-associated X protein (Bax) by downregulating the ubiquitin proteasome system (UPS). Romo1 inhibition downregulated the interaction between Bax and Parkin. Furthermore, Romo1 knockdown triggered the mitochondrial dysfunction and ROS generation. We validated the effect of combination in tumor xenograft model in vivo. In conclusion, our study demonstrates that Romo1 inhibition induces TRAIL-mediated apoptosis by identifying the novel mechanism associated with the Bax/Parkin interaction. We suggest that targeting of Romo1 is essential for the treatment of colorectal cancer and may be a new therapeutic approach in the future and contribute to the drug discovery.

Despite the importance of radiation therapy, there are few radiation-related markers available for use in clinical practice. A larger catalog of such biomarkers is required to help clinicians decide when radiotherapy should be replaced with a patient-specific treatment. Arachidonate 15-lipoxygenase (15-LOX-1) enzyme is involved in polyunsaturated fatty acid metabolism. When colorectal cancer (CRC) cells were exposed to radiation, 15-LOX-1 was upregulated. To verify whether 15-LOX-1 protects against or induces DNA damage, we irradiated sh15-LOX-1 stable cells. We found that low 15-LOX-1 is correlated with radioresistance in CRC cells. These data suggest that the presence of 15-LOX-1 can be used as a marker for radiation-induced DNA damage. Consistent with this observation, gene-set-enrichment analysis based on microarray experiments showed that UV_RESPONSE was decreased in sh15-LOX-1 cells compared to shCon cells. Moreover, we discovered that the expression of the histone H2A variant macroH2A2 was sevenfold lower in sh15-LOX-1 cells. Overall, our findings present mechanistic evidence that macroH2A2 is transcriptionally regulated by 15-LOX-1 and suppresses the DNA damage response in irradiated cells by delaying H2AX activation.

Although oxaliplatin is an effective chemotherapeutic drug for colorectal cancer (CRC) treatment, patients often develop resistance to it. Therefore, a new strategy for CRC treatment is needed. The purpose of this study was to determine the effect of cannabidiol (CBD), one of the components of the cannabis plant, in overcoming oxaliplatin resistance in CRC cells. We established oxaliplatin-resistant cell lines, DLD-1 R and colo205 R, in CRC DLD-1 and colo205 cells. Autophagic cell death was induced when oxaliplatin-resistant cells were treated with both oxaliplatin and CBD. Additionally, phosphorylation of nitric oxide synthase 3 (NOS3) was increased in oxaliplatin-resistant cells compared to that in parent cells. Combined treatment with oxaliplatin and CBD reduced phospho-NOS3 levels and nitric oxide (NO) production and resulted in the production of reactive oxygen species (ROS) by reducing the levels of superoxide dismutase 2, an antioxidant present in the mitochondria, causing mitochondrial dysfunction. Taken together, these results suggest that elevated phosphorylation of NOS3 is essential for oxaliplatin resistance. The combination of oxaliplatin and CBD decreased NOS3 phosphorylation, which resulted in autophagy, by inducing the overproduction of ROS through mitochondrial dysfunction, thus overcoming oxaliplatin resistance.

A spirometer is a medical device frequently used clinically for the diagnosis and prediction of lung disease. This study aimed to investigate the clinical usefulness of a hand-held spirometer (The Spirokit), compared with conventional spirometry in patients with chronic obstructive pulmonary disease (COPD). This study was conducted from February 2022 to October 2022. Measurements from 80 patients with COPD (male: 53, female: 27) were obtained using The Spirokit and PC-based pulmonary function test equipment, and the resulting values were compared and analyzed. For the concurrent validity comparison of The Spirokit, the intra-class correlation (ICC 2, 1), coefficients of variation (CVME), 95% limits of agreement (95% LOA), and Cohen’s Kappa Index were analyzed. The Spirokit showed high agreement (ICC: 0.929–0.989; 95% LOA: −0.525 to 2.559; and CVME: 0.05–0.08) with the PC-based pulmonary function tester. Using the Cohen’s kappa coefficients, the device showed high sensitivity, specificity, and accuracy scores of Pa: 0.90, Pc: 0.52, and K: 0.79, respectively, indicating considerable agreement. The Spirokit, a portable pulmonary function test device, is a piece of equipment with high validity and portability, with high potential for replacing PC-based pulmonary function test equipment.

This study was conducted to evaluate the effects of lysine cell mass (LCM) as an alternative lysine source in diets for weaning pigs on growth performance, diarrhea incidence, and blood profiles. In experiment 1, a total of 200 weaning pigs, with an average body weight (BW) of 6.89 ± 1.04 kg, were allotted into one of five treatments with four replicates of 10 pigs per pen in a randomized complete block design (RCBD). The dietary treatments were composed of LCM supplementation (0, 0.25, 0.5, 0.75, or 1.0%) with partial replacement of L-lysine·HCl (0 to 0.8% for phase 1 diets and 0 to 0.07% for phase 2 diets). The BW and feed intake were recorded at the end of each phase (d 0 to 14 for phase 1, d 14 to 35 for phase 2), and diarrhea incidence was checked daily throughout the experimental period. Blood samples were taken from the jugular vein of pigs at 2 weeks and 5 weeks to determine the blood profiles of weaning pigs. In experiment 2, a total of 144 weaning pigs with an average BW of 6.44 ± 1.19 kg were allotted into one of six treatments with six replicates of four pigs per pen in RCBD. The dietary treatments were composed of LCM supplementation (0 to 3.5% for phase 1 diets and 0 to 2.2% for phase 2 diets) with replacement of L-lysine·HCl from 0 to 100%. In experiment 1, partial replacement of L-lysine·HCl with 0 to 1% LCM did not affect growth performance and diarrhea incidence of pigs. An increase in the LCM supplementation from 0 to 1% with partial replacement of L-lysine·HCl had no influence on the blood urea nitrogen concentrations, whereas it resulted in a linear decrease (p < 0.05) in the serum IgG concentrations for 5 weeks. In experiment 2, increasing the dietary level of LCM with replacement of L-lysine·HCl quadratically decreased (p < 0.05) ADG and G–F ratio for phase 2 and G–F ratio for the overall period such that 100% replacement of L-lysine·HCl with LCM decreased ADG and G–F ratio of weaning pigs. An increase in the LCM supplementation with replacement of L-lysine·HCl tended to decrease linearly (p < 0.10) the diarrhea incidence of weaning pigs for the overall period and linearly decrease (p < 0.05) the serum IgG concentrations for 2 weeks. In conclusion, partial replacement of L-lysine·HCl with LCM from 0 to 1% had no negative impacts on the growth performance, but 100% replacement of L-lysine·HCl with LCM decreased the growth performance of weaning pigs. Therefore, LCM could be included in the diets for weaning pigs up to 2.8% and 1.76% for phase 1 and phase 2, respectively, as a substitute for L-lysine·HCl without detrimental effects on the performance of weaning pigs.