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Recent evidence revealed an inhibitory effect of circ-ITCH on the progression of papillary thyroid cancer via affecting the circ-ITCH/miR-22-3p/CBL axis. Rs4911154, an SNP located in circ-ITHC, was previously reported to be significantly associated with an increased risk of hepatocellular carcinoma. Ultrasound testing was used to evaluate the doubling time of thyroid nodules. 202 patients diagnosed with thyroid nodule disorders were divided into three groups according to their genotypes at rs4911154. We found that the A allele was correlated with a shortening doubling time of thyroid nodules. Moreover, the A allele contributed to reduced expression of circ-ITCH/CBL and increased expression of miR-22-3p. Besides, decreased tissue apoptosis was linked to the A allele. Luciferase assays indicated that miR-22-3p could effectively suppress the luciferase activities of CBL and circ-ITCH. Furthermore, manual up-regulation of miR-22-3p effectively suppressed the expression of CBL, while CBL siRNA apparently abolished circ-ITCH induced CBL upregulation, reduced proliferation and increased apoptosis of K1 and TPC-1 cells. A signaling pathway of circ-ITCH/miR-22-3p/CBL axis was established to explain the effect of SNP of circ-ITCH in thyroid tumor malignancy. Compared with the G allele, the A allele in rs4911154 contributed to the malignancy of thyroid nodules with decreased doubling time and down-regulated CBL expression.

BACKGROUND: Caspase-cleaved K18 (cK18) may accurately reflect hepatocyte apoptosis in patients with non-alcoholic steatohepatitis (NASH). However, NASH can also exist within the normal range of cK18. The aim of this study was to investigate the risk factors and characteristics of NASH within the normal serum levels of cK18. METHODS: In the study, 227 histopathologically confirmed non-alcoholic fatty liver disease (NAFLD) patients with normal cK18 levels (≤200 U/L), measured in serum using ELISA kits, were enrolled. The Rs738409 allele, coding patatin-like phospholipase domain-containing protein 3 (PNPLA3), was detected by MALDI-TOF mass spectrometry. Non-alcoholic steatohepatitis was defined as an NAFLD activity score (NAS) ≥5 with each part >0. RESULTS: The prevalence of NASH was 31.7% among NAFLD patients with normal serum cK18 levels. Compared with non-NASH, NASH had a higher possibility of occurrence with central obesity, insulin resistance, and the G allele of PNPLA3. The mean serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were higher in NASH patients. Moreover, ALT, AST, TC, LDL-C, central obesity, and the PNPLA3 G allele were risk factors for NASH in NAFLD patients with normal serum cK18 levels, with odds ratios of 1.01 (95% CI: 1.00, 1.02), 1.03 (95% CI: 1.01, 1.05), 1.33 (95% CI: 1.04, 1.68), 1.41 (95% CI: 1.03, 1.92), 2.19 (95% CI: 1.15, 4.18), and 2.48 (95% CI: 1.15, 5.36), respectively; all P < .05. CONCLUSIONS: The major risk factors for NASH were central obesity, AST, and the PNPLA3 G allele, in NAFLD with low hepatocyte apoptosis.

With the increasing application of tetracycline (TC) in medical treatment, animal husbandry and aquaculture in recent decades, high quantities of TC have been frequently detected in the aquatic environment, and accordingly TC-related toxicity and environmental pollution have become a global concern. The present study was performed to explore the toxicological influences of TC exposure at its environmentally relevant concentrations on the gills of tilapia Oreochromis niloticus, based on the alteration in histopathology, oxidative stress, inflammatory response, cell cycle, mitochondrial function, apoptosis, and transcriptomic analysis. Our findings revealed that TC exposure damaged the structure and function, induced oxidative stress, affected inflammatory responses, and reduced Na+/K+-ATPase (NKA) activity in the gills. TC also caused the inhibition in cell cycle, resulted in mitochondrial dysfunction and activated apoptosis. Further transcriptomic analysis indicated the extensive influences of TC exposure on the gill function, and immune system was the main target to waterborne TC exposure. These results elucidated that environmental TC had more complex toxicological effects on gills of fish than previously assessed, and provided novel insight into molecular toxicology of TC on fish and good basis for assessing the environmental risk of TC.

Enrofloxacin (ENR), one representative of fluoroquinolones widely used in husbandry, poses potential threats to aquatic organisms. However, its toxicological effect remained largely unknown. Here, we explored the influences of environmentally relevant concentration of ENR exposure on the gills of yellow catfish Pelteobagrus fulvidraco, a well-known freshwater teleost. After 10-weeks of waterborne ENR exposure at environmentally relevant concentrations, the gill tissues were collected and subsequently used for histopathology, enzyme activity, protein and mRNA expression analysis in yellow catfish. Our study revealed that waterborne ENR exposure reduced Na+/K+-ATPase activity, tight junction genes' expression and cytokines secretion, activated oxidative stress and induced apoptosis in gills. ENR exposure also activated MAPK signaling in a concentration-dependent manner. Thus, we demonstrated that environmentally relevant concentration of ENR exposure activated oxidative stress and MAPK pathway, resulted in immune dysfunction and induced intrinsic apoptosis. These results elucidated that ENR, as an environmental pollutant, had more complex toxicological effects on gills of fish than previously assessed, which provided novel insight into ENR toxicology and the assessment of its environmental risks.

Morphology and immune functions of Penaeus monodon haemocytes were analysed by flow cytometry (FCM). Basing on the relative size and granularity, there are three types of haemocyte identified by FCM, including hyaline cells (HC), semigranular cells (SGC) and granular cells (GC). GC and SGC were significantly larger than HC. GC contained more granules in the cytoplasm than the two other types. SGC were the most abundant cells, while HC were the least. The mean total apoptotic cell ratio was 5.09 % in the fresh shrimp haemocytes. SGC contributed most to the phagocytic activity, and HC contributed least, probably due to the great difference of percentage. GC had most mass of mitochondria and lysosome, and HC contained least. Defined by different characteristic of lysosomal mass, three subsets of haemocytes were observed. GC were most active in non-induced and zymosan-induced reactive oxygen species (ROS) production, while HC showed lowest oxidative activity. Both non-induced and zymosan-induced esterase activity (EA) in GC were higher than those in SGC and HC. The present flow cytometric analysis clearly demonstrated the variation in morphologic and immunological characterisation among the three haemocyte subpopulations. The facts that SGC account for most of the number of circulating haemocyte, while GC contain most organelles in relation to energy supply and immune defence, and have highest immune activites, suggesting that GC and SGC are the main haemocyte types involved in the cellular defence of P. monodon.