Evaluation of serum free fatty acids in chronic renal failure: evidence from a rare case with undetectable serum free fatty acids and population data.

BACKGROUND: Free fatty acid (FFA) accumulation in proximal tubules plays a fundamental role in the progress of kidney disease. Here, we reported a rare case with undetectable serum FFAs and further evaluated the changes of serum FFAs in patients with chronic renal failure (CRF). METHODS: We analyzed the clinical data of a rare case and 574 CRF patients. The mRNA expression of lipoprotein lipase (LPL), hepatic lipase (HL) and fatty acid synthase (FASN) were determined in the rare case and 30 age-matched healthy males with qPCR. RESULTS: This rare case had serious proteinuria, hyperglycemia, lipid disorders and bilateral renal glomerular filtration dysfunction. Compared with healthy males, this case showed a 1.49-fold increase of LPL expression (P < 0.01), a 3.38-fold reduction of HL expression (P < 0.001), and no significant change of FASN expression (P > 0.05). In total, 21.6% of CRF patients showed abnormal FFAs. Biochemical parameters such as blood urea nitrogen (BUN) and creatinine (CREA) significantly differed among groups with low-, normal- or high-level-FFAs. Moreover, serum FFAs was found to be associated with BUN. FFAs decreased in the group with higher BUN (> 17.4 mmol/L) and in the group with lower estimated glomerular filtration rate (eGFR) (< 15 mL/min/1.73m2). CONCLUSIONS: The proteinuria, HL low expression and renal function failure may contribute to the FFA reduction, which might imply that the renal function is severely damaged.

A case of West syndrome and global developmental delay in a child with a heterozygous mutation in the TBL1XR1 gene: A case report.

BACKGROUND: TBL1XR1, also known as IRA1 or TBLR1, encodes a protein that is localized in the nucleus and is expressed in most tissues. TBL1XR1 binds to histones H2B and H4 in vitro and functions in nuclear receptor-mediated transcription. TBL1XR1 is also involved in the regulation of the Wnt-ß-catenin signaling pathway. Mutations in the TBL1XR1 gene impair the Wnt-ß-catenin signaling pathway's ability to recruit Wnt-responsive element chromatin, affecting brain development. Mutations in this gene cause various clinical phenotypes, including Pierpont syndrome, autism spectrum disorder, speech and motor delays, mental retardation, facial dysmorphism, hypotonia, microcephaly, and hearing impairment. CASE SUMMARY: A 5-month-old female child was admitted with "episodic limb tremors for more than 1 month." At the time of admission, the child had recurrent episodes of limb tremors with motor retardation and a partially atypical and hypsarrhythmic video electroencephalogram. It was determined that a heterozygous mutation in the TBL1XR1 gene caused West syndrome and global developmental delay. Recurrent episodes persisted for 6 months following oral treatment with topiramate; the addition of oral treatment with vigabatrin did not show any significant improvement, and the disease continued to recur. The child continued to have recurrent episodes of limb tremors at follow-up until 1 year and 3 months of age. Additionally, she developed poor eye contact and a poor response to name-calling. CONCLUSION: We report the case of a child with West syndrome and a global developmental delay caused by a heterozygous mutation in the TBL1XR1 gene. This study adds to our understanding of the clinical phenotype of TBL1XR1 mutations and provides a realistic and reliable basis for clinicians.

Exosome plays an important role in the development of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most malignant cancers around the world. However, the early biomarkers for its detection and treatment are limited currently. Exosomes, classified as intercellular messenger shuttling their cargoes between cells, regulate cell differentiation and tissue development. They contain messenger RNA (mRNA), microRNA (miRNA), long non-coding RNA (lncRNA), circular RNA (circRNA), proteins, lipids and transcription factors. Therefore, exosomes play a crucial role in the development of HCC. In this review, we highlight the exosomal cargoes which could serve as biomarkers for the prediction and diagnosis of HCC. Exosomes are involved in metastases of HCC and they show great potential in immunotherapy and drug resistance mechanism. In summary, exosome suggests new clues in clinical application of HCC.

Link Between m6A Modification and Cancers.

N6-methyladenosine (m6A) epitranscriptional modification has recently gained much attention. Through the development of m6A sequencing, the molecular mechanism and importance of m6A have been revealed. m6A is the most abundant internal modification in higher eukaryotic mRNAs, which plays crucial roles in mRNA metabolism and multiple biological processes. In this review, we introduce the characteristics of m6A regulators, including "writers" that create m6A mark, "erasers" that show demethylation activity and "readers" that decode m6A modification to govern the fate of modified transcripts. Moreover, we highlight the roles of m6A modification in several common cancers, including solid and non-solid tumors. The regulators of m6A exert enormous functions in cancer development, such as proliferation, migration and invasion. Especially, with the underlying mechanisms being uncovered, m6A and its regulators are expected to be the targets for the diagnosis and treatment of cancers.