Tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2 or TNFAIP8L2) is a newly described negative immune regulator and is closely associated with various tumors. However, the expression and roles of TIPE2 in PTC is unknown.

Familial hypercholesterolemia (FH) is an inherited disorder characterized by elevation of serum cholesterol bound to low-density lipoprotein. Mutations in LDLR are the major factors responsible for FH. In this study, we recruited a four-generation Chinese family with FH and identified the clinical features of hypercholesterolemia. All affected individuals shared a novel indel mutation (c.1885_1889delinsGATCATCAACC) in exon 13 of LDLR. The mutation segregated with the hypercholesterolemia phenotype in the family. To analyze the function of the indel, we established stable clones of mutant and wild-type LDLR in Hep G2 cells. The mutant LDLR was retained in the endoplasmic reticulum (ER) and failed to glycosylate via the Golgi. Moreover, the membrane LDLR was reduced and lost the ability to take up LDL. Our data also expand the spectrum of known LDLR mutations.

Mutations in Connexin-31 (Cx31) are associated with multiple human diseases including erythrokeratodermia variabilis (EKV). The molecular action of Cx31 pathogenic mutants remains largely elusive. We report here that expression of EKV pathogenic mutant Cx31R42P induces cell death with necrotic characteristics. Inhibition of hemichannel activity by a connexin hemichannel inhibitor or high extracellular calcium suppresses Cx31R42P-induced cell death. Expression of Cx31R42P induces ER stress resulting in reactive oxygen species (ROS) production, in turn, to regulate gating of Cx31R42P hemichannels and Cx31R42P induced cell death. Moreover, Cx31R42P hemichannels play an important role in mediating ATP release from the cell. In contrast, no hemichannel activity was detected with cells expressing wildtype Cx31. Together, the results suggest that Cx31R42P forms constitutively active hemichannels to promote necrotic cell death. The Cx31R42P active hemichannels are likely resulted by an ER stress mediated ROS overproduction. The study identifies a mechanism of EKV pathogenesis induced by a Cx31 mutant and provides a new avenue for potential treatment strategy of the disease.

Osteosarcoma (OS) has a high incidence, malignity, and frequency of recurrence and metastasis. In this study, we aimed to explore the potential anti-cancer effects of Astragalus polysaccharides (APS) on human OS MG63 cells as well as underlying mechanisms. Viability of MG63 cells was assessed by CCK-8 assay to determine the adequate concentration of APS. Then, effects of APS on MG63 cell proliferation, cell cycle distribution, apoptosis, and migration and invasion were analyzed by BrdU incorporation, PI staining, flow cytometry, and transwell assays, respectively. The expression levels of proteins involved in these physiological processes were assessed by western blot analysis. Afterwards, miR-133a level in APS-treated cells was determined by qRT-PCR, and whether APS affected MG63 cells through regulation of miR-133a was determined. Finally, the activation of c-Jun N-terminal protein kinase (JNK) pathway was detected. We found that APS treatment suppressed the viability, proliferation, migration, and invasion of MG63 cells, as well as induced cell apoptosis. Moreover, APS enhanced the expression of miR-133a in MG63 cells. Knockdown of miR-133a reversed the APS treatment-induced MG63 cell proliferation, migration and invasion inhibition, as well as cell apoptosis. Furthermore, APS inactivated JNK pathway in MG63 cells. Knockdown of miR-133a reversed the APS treatment-induced inactivation of JNK pathway in MG63 cells. To conclude, APS repressed proliferation, migration, and invasion while induced apoptosis of OS MG63 cells by up-regulating miR-133a and then inactivating JNK pathway.

Exenatide is a stable analogue of glucagon-like peptide 1 that can reduce postprandial hyperglycemia and has been utilized as adjunctive therapy for type 1 diabetes mellitus (T1DM). The human umbilical cord is a rich source of MSCs, and human umbilical cord mesenchymal stem cells (hUCMSCs) also show potential to enhance insulin secretion. Here, we aimed to explore the effects of hUCMSCs carrying exenatide in T1DM and further identify the possible mechanisms involved.

Existing findings regarding the relationship between comorbidities and the severity of coronavirus disease 2019 (COVID-19) are inconsistent and insufficient. The aim of this study was to evaluate the association between different comorbidities and the severity of COVID-19.

Histone H3 (H3K4) demethylase JARID1B is aberrantly upregulated in many types of tumor and has been proposed to function as oncogene. Here we show that JARID1B is elevated in moderate and high-differentiated human hypopharyngeal squamous cell carcinoma (HPSCC) compared with low-differentiated HPSCC. Overexpression of JARID1B in FaDu cells increased epithelial differentiation marker K10 expression and inhibited cell proliferation. JARID1B and K10 mRNA expression is high correlated in HPSCC patients. Mechanistically, we found JARID1B directly bound to PI3K/AKT signaling inhibitor SHIP1 gene promoter and decreased SHIP1 gene expression. Activation of downstream AKT resulted in increased β-catenin signaling, by which promoted target genes Fra-1 and Jun, together with other AP-1 transcription factors, leading to K10 expression. Forced expression of SHIP1 rescued JARID1B-induced phenotypes on FaDu cell differentiation and proliferation. Taken together, our findings provide first evidence that elevated expression of JARID1B has a critical role in promoting HPSCC differentiation and inhibiting proliferation, suggesting JARID1B may function as a tumor suppressor in squamous cell cancers and implying a novel important therapeutic strategy of HPSCC.

Lipoprotein lipase (LPL) is widely expressed in skeletal muscles, cardiac muscles as well as adipose tissue and involved in the catabolism of triglyceride. Herein we have systematically characterized two novel loss-of-function mutations in LPL from a Chinese family in which afflicted members were manifested by severe hypertriglyceridemia and recurrent pancreatitis. DNA sequencing revealed that the proband was a heterozygote carrying a novel c.T928C (p.C310R) mutation in exon 6 of the LPL gene. Another member of the family was detected to be a compound heterozygote who along with the c.T928C mutation also carried a novel missense mutation c.A1187T (p.E396V) in exon 8 of the LPL gene. Furthermore, COS-1 cells were transfected with lentiviruses containing the mutant LPL genes. While C310R markedly reduced the overall LPL protein level, COS-1 cells carrying E396V or double mutations contained similar overall LPL protein levels to the wild-type. The specific activity of the LPL mutants remained at comparable magnitude to the wild-type. However, few LPL were detected in the culture medium for the mutants, suggesting that both mutations caused aberrant triglyceride catabolism. More specifically, E396V and double mutations dampened the transport of LPL to the cell surface, while for the C310R mutation, reducing LPL protein level might be involved. By characterizing these two novel LPL mutations, this study has expanded our understanding on the pathogenesis of familial hypertriglyceridemia (FHTG).

Diabetic neuropathy (DN) is one of the most common diabetic complications that results in an increase in patient discomfort and pain. The present study demonstrated that mesenchymal stem cells (MSCs) or resveratrol (RSV) may improve diabetic hyperglycemia and neuropathy. The aim of the present study was to investigate the combined effect of MSCs and RSV on DN. A total of 100 non-obese diabetic mice were divided into the following six groups: Normal control, MSCs, RSV, MSCs + RSV, insulin and diabetic control groups. Following homologous therapy, the levels of blood glucose and C-peptide, islets, nuclear factor (NF)-κB, nerve growth factor (NGF) and myelin basic protein (MBP), and the sciatic nerve structure in each group were examined and evaluated. Following the administration of therapy, the levels of blood glucose and C-peptide in mice in the MSCs + RSV group were significantly improved when compared with the other diabetic groups, and the dosage of insulin therapy required was the lowest among the six experimental groups (P<0.05). The levels of NGF, MBP and NF-κB in the MSCs + RSV group were significantly improved compared with the MSCs and RSV groups (P<0.05). Furthermore, the diameter of the axon, number of myelinated nerve fibers and the depth of the myelin sheath in the MSCs + RSV group were greatest among the five examined groups (excluding the control). The combination of RSV and MSCs could relieve hyperglycemia and improve DN. This indicated that the combination of RSV and MSCs may be a novel therapeutic method for the treatment of DN.

Stem cells provide a promising candidate for the treatment of the fatal pediatric dilated cardiomyopathy (DCM). This study aimed to investigate the effects of intramuscular injection of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) on the cardiac function of a DCM rat model.

Although several epidemiological studies assessed the relationship between fasting plasma glucose (FPG) and serum uric acid (SUA) levels, the results were inconsistent. A cross-sectional study was conducted to investigate this relationship in Chinese individuals with normal glucose tolerance.

Familial hypertriglyceridemia (FHTG) is an autosomal dominant disorder of lipoprotein metabolism, partly caused by mutations in the LPL gene, which encodes for the lipoprotein lipase. LPL deficiency can impair triglyceride hydrolysis which causes elevated plasma triglyceride levels. An induced pluripotent stem cell (iPSC) line was generated from peripheral blood mononuclear cells (PBMCs) of a 53 years-old male patient with FHTG who had a heterozygous p.C310R (c.928 T > C) mutation in the LPL gene based on the sendai virus delivery system. The cellular model will offer a powerful tool to investigate pathogenic mechanisms in FHTG and to develop a treatment for FHTG.