BackgroundThyroid metastases from colorectal cancer (CRC) are rare, both in clinical practice and in the literature; hence, their diagnosis, appropriate treatment, and prognostic factors require further investigations.MethodsA retrospective analysis was performed for four cases of thyroid metastases from CRC, treated in our center between January 2005 and December 2015, and the relevant literature was searched using PubMed, resulting in the identification of 17 patients with detailed information available. The clinical data and follow-up information of our patients and the previously reported cases were collected and compared.ResultsThe median age of the 21 patients was 59 years (44.5 and 66 years for our patients and the previously reported cases, respectively). Fifteen (71.4%) primary tumors were distributed throughout the distal colon or rectum (75% [3/4] in our center and 70.5% [12/17] in the previously reported cases). According to our analysis, we found that 81.0% of patients (17/21) showed concomitant lung metastasis. Among them, all four patients in our center showed lung metastasis, and 75% (3/4) developed thyroid metastases after the lung metastasis. In the previously reported cases, the corresponding proportions were 76.5 and 76.5% (13/17) of patients, respectively. The median time after primary tumor diagnosis to thyroid metastasis development was 28 months (26 months in our center and 35 months in the previously reported cases). One patient with advanced CRC in our center died 5 months after the thyroid metastasis was identified, while the remaining three patients are currently alive (longest follow-up time, 27 months). The median survival time after thyroid metastasis during 3 years of follow-up of the previously reported 17 patients was 12 months. There was no difference in the overall survival between patients treated non-surgically (8/21) and patients undergoing thyroidectomy alone or thyroidectomy with adjuvant therapy (13/21) (p = 0.388). In addition, we found that the overall survival of the patients whose other metastases were treated with radical treatment was superior to that in those treated with palliative treatment (p = 0.022).ConclusionsThyroid metastases from CRC are rare in clinical practice and are a manifestation of advanced CRC. The prognosis of patients with thyroid metastases from CRC is related to various factors, including the grade of malignancy of the primary lesion, the presence of other metastases, and whether the metastases are timely diagnosed and a radical treatment strategy is employed.

The gut microbiota plays an important role in inflammatory diseases. Metabolites in the three metabolic pathways of tryptophan (Trp), histidine (His), and phenylalanine (Phe) can affect various inflammatory conditions, such as obesity, diabetes, arthritis, colitis, atherosclerosis, and neuroinflammation. We established an LC–MS/MS method to measure 17 metabolites—Trp, 3-indole-acetic acid (Iaa), 3-indole-lactate (Ila), 3-indole-propionic acid (Ipa), 3-indole formaldehyde (Iald), kynurenine (Kn), kynurenic acid (Kyna), 3-Hydroxyanthranilic acid (3-Haa), His, 3-methylhistidine (3-Mhis), histamine (Hist), imidazole propionic acid (Imp), 4-imidazoacetic acid (Imaa), urocanic acid (Ua), Phe, phenylethylamine (Pea), and hippuric acid (Ha)—in the three metabolic pathways. The method exhibited high sensitivity and good selectivity, linearity, accuracy, precision, stability; and recovery rate; all met the requirements of biological sample analysis. By establishing a rheumatoid arthritis (RA) model of Sprague–Dawley rats and performing 16S rRNA sequencing on their feces, it was found that there was dysbiosis, including changes in phylum level, genus level, and α biodiversity of gut bacteria. The contents of the microbiota metabolites Iaa and Ipa in the model group were significantly decreased, and those of Iald, Kn, Kyna, Ha, and Imp were significantly increased. The common therapeutic drugs Tripterygium glycosides, total glucosides of peony, and their main active ingredients were screened by in vitro incubation with gut bacteria: it was found that Tripterygium glycosides and their active ingredients could lead to a variation in metabolites in the Trp and Phe pathways. Total glucosides and active components of peony could lead to a variation in metabolites in the Phe pathway of the gut microbiota.

Timosaponin BII is one of the most abundant Anemarrhena saponins and is in a phase II clinical trial for the treatment of dementia. However, the pharmacological activity of timosaponin BII does not match its low bioavailability. In this study, we aimed to determine the effects of gut microbiota on timosaponin BII metabolism. We found that intestinal flora had a strong metabolic effect on timosaponin BII by HPLC-MS/MS. At the same time, seven potential metabolites (M1-M7) produced by rat intestinal flora were identified using HPLC/MS-Q-TOF. Among them, three structures identified are reported in gut microbiota for the first time. A comparison of rat liver homogenate and a rat liver microsome incubation system revealed that the metabolic behavior of timosaponin BII was unique to the gut microbiota system. Finally, a quantitative method for the three representative metabolites was established by HPLC-MS/MS, and the temporal relationship among the metabolites was initially clarified. In summary, it is suggested that the metabolic characteristics of gut microbiota may be an important indicator of the pharmacological activity of timosaponin BII, which can be applied to guide its application and clinical use in the future.

An increasing number of studies have shown that circRNAs are closely related to the carcinogenesis and development of prostate cancer (PCa). However, little is known about the effect of the biological functions of circRNAs on the enzalutamide resistance of PCa. Through bioinformatic analysis and experiments, we investigated the expression pattern of circRNAs in enzalutamide-resistant PCa cells. Quantitative real-time PCR was used to detect the expression of circRAB3IP, and plasmids that knock down or overexpress circRAB3IP were used to evaluate its effect on the enzalutamide sensitivity of PCa cells. Mechanistically, we explored the potential regulatory effects of eIF4A3 and LEF1 on the biogenesis of circRAB3IP. Our in vivo and in vitro data indicated that increased expression of circRAB3IP was found in enzalutamide-resistant PCa, and knockdown of circRAB3IP significantly enhanced enzalutamide sensitivity in PCa cells. However, upregulation of circRAB3IP resulted in the opposite effects. Further mechanistic research demonstrated that circRAB3IP could regulate the expression of serum and glucocorticoid-regulated kinase 1 (SGK1) by serving as a sponge that directly targets miR-133a-3p/miR-133b. Then, we showed that circRAB3IP partially exerted its biological functions via SGK1 signaling. Furthermore, we discovered that eIF4A3 and LEF1 might increase circRAB3IP expression in PCa.