Hemin enhances the 5-aminolevulinic acid-photodynamic therapy effect through the changes of cellular iron homeostasis.

BACKGROUND: Photodynamic therapy (PDT) has been utilized as a promising alternative cancer treatment due to its minimum invasiveness over the years. Exogenous 5-aminolevulinic acid (ALA) triggers protoporphyrin IX (PpIX) accumulation, which happens in cancer cells. However, certain types of cancer exhibit reduced effectiveness in the PpIX accumulation mechanism. This study aimed to determine the effect of ALA-PDT combination with hemin on gastric carcinoma TMK-1 cells. METHODS: This study utilized TMK-1 gastric cancer cell line to evaluate PpIX, ROS, and Fe2+ accumulation following the administration of ALA, hemin, and a combination of ALA and hemin PDT. We also evaluate the mRNA expressions related to iron homeostasis and treatment impacts on cell viability. RESULTS: The co-addition of ALA and hemin PDT for 4 h of treatment resulted in a significant decrease in cell viability by up to 18 %. While ALA-PDT enhanced PpIX metabolism, the addition of hemin influenced both the production of reactive oxygen species (ROS) and cellular iron homeostasis by inducing Fe2+ accumulation and affecting mRNA levels of IRP, Tfr1, Ferritin, NFS1, and SDHB. CONCLUSION: These findings suggest that the addition of ALA and hemin enhances phototoxicity in TMK-1 cells. The combination of ALA and hemin with PDT induces cell death, evidenced by increased cytotoxicity properties such as PpIX and ROS, along with significant changes in TMK-1 gastric cancer iron homeostasis. Therefore, the combination of ALA and hemin could be one of the alternatives in photodynamic therapy for cancer in the future.

Repeated Inhalation of Peppermint Essential Oil Improves Exercise Performance in Endurance-Trained Rats.

Peppermint essential oil, being natural and safe, with antioxidant and anti-inflammatory properties, has long been a research interest in relieving fatigue and improving exercise performance. However, the related studies report controversial results, and the mechanisms remain unclear. Here we found that inhalation of peppermint essential oil significantly extended the exhaustion time in rats subjected to 2-week weight-bearing swimming training. Sprague-Dawley rats were subjected to a 2-week weight-loaded forced swimming regimen. Prior to each swimming session, the rats were administered peppermint essential oil via inhalation. An exhaustive swimming test was performed at the end of the protocol. Rats treated with essential oil had significantly extended time to exhaustion compared with exercised rats without essential oil treatment. In addition, treated rats also showed reduced oxidative damage induced by endurance exercise. Notably, the rats receiving two-week essential oil inhalation while not subjected to swimming training did not show improved exercise performance. The findings demonstrate that repeated inhalation of peppermint essential oil enhances the effects of endurance training and improves exercise performance partially by preventing oxidative damage.

The obesity paradox in patients with colorectal cancer: a systematic review and meta-analysis.

CONTEXT: Obesity is widely regarded as an established risk factor for colorectal cancer (CRC). However, recent studies have shown that lower mortality and better cancer-specific survival were observed in CRC patients with elevated body mass index (BMI), an example of the obesity paradox, which is the inverse correlation between obesity and mortality in some populations. OBJECTIVE: The aim of this systematic review and meta-analysis was to investigate the association between BMI and CRC outcomes. DATA SOURCES: PubMed, Web of Science, MEDLINE, the Cochrane Library, and Embase databases were searched for relevant articles published from inception to December 31, 2020. STUDY SELECTION: Studies comparing the prognosis of CRC patients with obesity or overweight with that of normal-weight CRC patients were eligible. DATA EXTRACTION: Data were extracted by 2 reviewers independently; differences were resolved by a third reviewer. BMI was classified according to WHO categories. DATA ANALYSIS: To assess the prognostic effects of different BMI categories in CRC patients, hazard ratios and 95%CIs of overall survival, disease-free survival, and cancer-specific survival were extracted from included articles. RESULTS: Sixteen studies (55 391 patients in total) were included. Higher BMI was significantly associated with more favorable CRC outcomes. Compared with normal-weight patients, underweight patients had worse overall survival (HR = 1.26; 95%CI, 1.15-1.37) and disease-free survival (HR = 1.19; 95%CI, 1.11-1.27, while patients with overweight had better overall survival (HR = 0.92; 95%CI, 0.86-0.99), disease-free survival (HR = 0.96; 95%CI, 0.93-1.00), and cancer-specific survival (HR = 0.86; 95%CI, 0.76-0.98). Patients with morbid obesity had worse overall survival (HR = 1.12; 95%CI, 1.02-1.22) and disease-free survival (HR = 1.15; 95%CI, 1.07-1.24) than normal-weight patients. There was no significant difference in cancer-specific survival between patients with obesity (HR = 0.94; 95%CI, 0.76-1.16) and patients with normal weight, nor between patients with underweight and patients with normal weight (HR = 1.14; 95%CI, 0.82-1.58). CONCLUSIONS: CRC patients with a higher BMI appear to have reduced mortality compared with normal-weight CRC patients, even though higher BMI/obesity is an established determinant for the development of CRC. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42020202320.

Noninvasive tumor imaging with high-frequency ultrasound and microPET in small animals.

In this study, we used a micro-ultrasound (microUS) system that we developed in-house as an alternative method for tumor growth calipers. In addition, microUS was combined with small-animal positron-emission tomography (microPET) for tumor metastatic assessment. MicroUS provides anatomical information that can be used for tumor volume measurements while microPET is a functional imaging method with positron-emitting radiophamaceuticals, such as 18F-labeled deoxyglucose, [18F]FDG. In this study, microUS and microPET were performed in a mouse tumor longitudinal study (2-8 weeks), both with 3D tumor segmentation and volume measurements. Compared with vernier calipers, microPET generally overestimated tumor volumes during weeks 2-4 due to its inadequate spatial resolution. During weeks 5-8, standard deviations of microPET results were large due to tumor hypoxia or necrosis. On the contrary, microUS tumor volume measurements were more reliable as they were less affected by these factors. Nonetheless, microUS is not able to provide functional information similar to that provided by microPET. Therefore, microUS and microPET are complementary to each other as microUS has superior spatial resolution and microPET provides functional information, such as hypoxia or necrosis in the progression of the tumor. With image registration and fusion, the combination can be a valuable tool for cancer research.

Non-Invasive imaging of small-animal tumors: high-frequency ultrasound vs. MicroPET.

Tumor volume measurement on small animals is important but currently invasive. We employ ultrasonic micro-imaging (UMI) in this study and demonstrate its feasibility. In addition, we use small animal positron emission tomography (microPET) as a preliminary effort to develop multi-modality small animal imaging techniques. The tumor growth curve from UMI is also compared to radioactivity from microPET. Both UMI and [18F] FDG microPET imaging were performed on C57BL/6J black mice bearing WF-3 ovary cancer cells at various stages from the second week till up to the eighth week. Segmentation and 3D reconstruction were also done. The growth curve was obtained in vivo noninvasively by UMI. The cell doubling time was 7.46 days according to UMI. This result was compared with vernier caliper measurement and radioactivity counting by microPET. In microPET, we obtained the time-activity curves from the tumor and the tumor-surrounding tissue. The tumor-to-normal-tissues ratios reached maximum at the fifth week after tumor cell implantation.