Peripheral tear of the triangular fibrocartilage complex: diagnostic accuracy of magnetic resonance imaging and diagnostic performance of the primary and secondary signs.

OBJECTIVE: This study is to assess the diagnostic performance of magnetic resonance imaging (MRI) findings for type 1B triangular fibrocartilage complex (TFCC) tear of the wrist. MATERIALS AND METHODS: This study retrospectively enrolled 78 patients to examine the diagnostic performance of preoperative MRI examinations in patients with type 1B TFCC tears. Thirty-nine participants had confirmed type 1B TFCC tear. The control group included 39 patients who were randomly selected from 1157 patients who underwent MRI for wrist pain. Both groups underwent a review of 19 MRI findings by two independent radiologists, and the correlation between each diagnostic finding and type 1B TFCC tear was assessed using the chi-squared test. The 19 MRI findings comprised eight primary signs of abnormalities in the distal or proximal lamina, in conjunction with 11 secondary signs suggestive of abnormalities in the surrounding structures. RESULTS: The TFCC tear group demonstrated a significantly higher incidence of two primary MRI signs, i.e., fiber discontinuity and signal alteration in the distal lamina, as observed by both readers (R1, 74.4% vs. 38.5%, p = 0.003, and 87.2% vs. 43.6%, p < 0.001; R2, 74.4% vs. 35.9%, p = 0.001, and 87.2% vs. 53.8%, p < 0.003, respectively). Reader 2 identified a higher prevalence of two additional primary MRI signs: fiber discontinuity and signal alteration in the proximal lamina (all p < 0.05). None of the 11 secondary MRI signs demonstrated statistically significant associations with type 1B TFCC. CONCLUSION: MRI manifestations of fiber discontinuity and signal alteration in the distal lamina may provide predictive markers for type 1B TFCC wrist tear.

Translationally controlled tumor protein restores impaired memory and altered synaptic protein expression in animal models of dementia.

This study describes the effects of translationally controlled tumor protein (TCTP) on mice with memory impairment caused by scopolamine (SCO) administration. Specifically, memory functions and expression levels of hippocampal synaptic proteins in 7- to 12-month-old SCO-treated wild-type (WT-SCO) mice were compared to those of TCTP-overexpressing (TG) and TCTP knocked-down (KD) mice similarly treated with SCO. Passive-avoidance tasks were performed with WT, TG, and KD mice for four weeks after intraperitoneal injection of SCO or saline followed by an acquisition test. After completing behavioral studies, hippocampi of all mice groups were collected and their synaptic protein contents were subjected to Western blotting or immunohistochemical analyses, and compared with those of 5x familial Alzheimer's disease (5xFAD) mice and postmortem AD patients. Results of passive avoidance tests revealed that SCO-induced memory impairment was repaired in TCTP-TG mice, but not in TCTP-KD mice. Hippocampal expression levels of synaptophysin, synapsin-1, and PSD-95 were increased in TCTP-TG mice treated with SCO (TG-SCO) but decreased in TCTP-KD mice treated with SCO (KD-SCO). Decreased levels of TCTP, synaptophysin, and PSD-95 were also found in hippocampi of 5xFAD mice and AD patients. Expression levels of p-CREB/CREB and brain-derived neurotrophic factor (BDNF) in TCTP-TG and TG-SCO mice were similar to or increased compared to those in WT mice, but decreased in TCTP-KD and KD-SCO mice. BDNF immunoreactivity was restored in CA1 regions of hippocampi of TG-SCO mice, but not in KD-SCO mice. These results suggest that TCTP can restore damaged memory in mice possibly through restored synaptic protein expression.

Synthesis of 1,4-Dialkoxynaphthalene-Based Imidazolium Salts and Their Cytotoxicity in Cancer Cell Lines.

In this study, we designed and synthesized novel 1,4-dialkoxynaphthalene-2-alkyl imidazolium salt (IMS) derivatives containing both 1,4-dialkoxynaphthalene and imidazole, which are well known as pharmacophores. The cytotoxicities of these newly synthesized IMS derivatives were investigated in order to explore the possibility of using them to develop anticancer drugs. It was found that some of the new IMS derivatives showed good cytotoxic activities. In addition, an initial, qualitative structure-activity relationship is presented on the basis of observations of activity changes corresponding to structural changes.

Meclizine, a piperazine-derivative antihistamine, binds to dimerized translationally controlled tumor protein and attenuates allergic reactions in a mouse model.

Translationally controlled tumor protein (TCTP), a highly conserved protein present in most eukaryotes, is involved in numerous biological processes. Only the dimeric form of TCTP (dTCTP) formed during inflammatory conditions exhibits cytokine-like activity. Therefore, dTCTP is considered as a therapeutic target for allergic diseases. Because monomeric TCTP (mTCTP) and dTCTP share a high topological similarity, we hypothesized that small molecules interacting with mTCTP would also bind to dTCTP and interfere with dTCTP-based cellular processes. In this study, nine compounds listed in the literature as interacting with mTCTP were investigated for their ability to suppress the activity of extracellular dTCTP in bronchial epithelial cells. It was found that one of the nine, meclizine, a piperazine-derivative antihistamine, significantly reduced IL-8 release and suppressed the NF-κB pathway. The direct interaction of meclizine with dTCTP was confirmed by surface plasmon resonance (SPR). Also, we found that meclizine can attenuate ovalbumin (OVA)-induced airway inflammation in mice. Therefore, meclizine might be a potential anti-allergic drug as an inhibitor for dTCTP.

Dimeric translationally controlled tumor protein-binding peptide 2 attenuates imiquimod-induced psoriatic inflammation through induction of regulatory T cells.

Psoriasis is a chronic skin inflammation caused by a dysfunctional immune system, which causes systemic inflammation in various organs and tissues. Due to the risk of systemic inflammation and recurrence of psoriasis, it is important to identify the critical targets in the pathogenesis of psoriasis and develop targeted therapeutics. Dimerized translationally controlled tumor protein (dTCTP) promotes immune cell activation as a pro-inflammatory cytokine and plays a role in developing allergic diseases such as asthma and rhinitis. Here, we sought to explore whether dTCTP and its inhibition contributed to the development and control of imiquimod (IMQ)-induced psoriasis. Topical application of IMQ inflamed the skin of the back and ear, increased inflammatory cytokines, and decreased regulatory T cell markers. Interestingly, TCTP was significantly increased in inflamed skin and immune cells such as T cells, B cells, and macrophages after IMQ treatment and was secreted into the serum to undergo dimerization. Extracellular dTCTP treatment selectively suppressed regulatory T (Treg) cells, not other effector T helper (Th) cells, and increased M1 macrophages. Moreover, dTCTP-binding peptide 2 (dTBP2), a dTCTP inhibitor peptide, effectively attenuated the systemic inflammatory responses, including Th17 cell response, and alleviated psoriatic skin inflammation. dTBP2 blocked dTCTP-mediated Treg suppression and stimulated the expression of Treg cell markers in the spleen and inflammatory skin lesions. These results suggest that dTCTP dysregulated immune balance through Treg suppression in psoriatic inflammation and that functional inhibition of dTCTP by dTBP2 maintained immune homeostasis and attenuated inflammatory skin diseases by expanding Treg cells.

Overexpression of translationally controlled tumor protein ameliorates metabolic imbalance and increases energy expenditure in mice.

BACKGROUND/OBJECTIVES: Translationally controlled tumor protein (TCTP) exhibits numerous biological functions. It has been shown to be involved in the regulation of glucose. However, its specific role in metabolism has not yet been clearly elucidated. Here, we aimed to assess the effect of TCTP overexpression on metabolic tissues and systemic energy metabolism. SUBJECTS/METHODS: We investigated whether TCTP can ameliorate the metabolic imbalance that causes obesity using TCTP-overexpressing transgenic (TCTP TG) mice. The mice were subjected to biochemical, morphological, physiological and protein expression studies to define the role of TCTP in metabolic regulation in response to normal chow diet (NCD) compared to high-fat diet (HFD) conditions, and cold environment. RESULTS: We found that TCTP TG mice show improved metabolic homeostasis under both of NCD and HFD conditions with simultaneous enhancements in glucose tolerance and insulin sensitivity. In particular, we found coincident increases in energy expenditure with significant upregulation of uncoupling protein 1 (UCP1) in the brown adipose tissue (BAT). Moreover, TCTP overexpressing mice exhibit significantly enhanced adaptive thermogenesis of BAT in response to cold exposure. CONCLUSIONS: Overexpression of TCTP ameliorated systemic metabolic homeostasis by stimulating UCP1-mediated thermogenesis in the BAT. This suggests that TCTP may function as a modulator of energy expenditure. This study suggests TCTP may serve as a therapeutic target for obesity and obesity-associated metabolic disorders including type 2 diabetes.

Mechanical thrombectomy in patients with acute cancer-related stroke: is the stent retriever alone effective?

BACKGROUND: The optimal first-line mechanical thrombectomy (MT) method in cancer-related stroke (CRS) patients with emergent large vessel occlusion (ELVO) remains largely unknown. The aim of this study is to evaluate the efficacy and safety between contact aspiration (CA) first-line thrombectomy and stent retriever (SR) first-line thrombectomy in CRS patients. METHODS: Sixty-two CRS patients with ELVO, who underwent MT between January 2013 and October 2019 at our institution, were retrospectively analyzed. Patients were divided into two groups based on the first-line MT method and compared: the CA group (n=28), which included those who received CA alone or combined CA with SR, and the SR group (n=34), which included those who received conventional SR alone. RESULTS: Overall, reperfusion was successful in 75.8% (47/62) of CRS patients, and a good clinical outcome at 90 days was observed in 17.7%. The CA group showed a higher rate of successful reperfusion (89.3% vs 64.7%, P=0.025) shorter procedure time (22 vs 42 min; P=0.029), higher rate of first pass effect (35.7% vs 11.8%, P=0.025), and lower number of passes (1 vs 3, P=0.023) when compared with the SR group. The procedural and hemorrhagic complication rates were similar between the CA and SR groups. The first-line contact aspiration (OR 11.624, 95% CI 1.041 to 129.752; P=0.046) was an independent predictor of successful reperfusion. CONCLUSIONS: Among patients with CRS, CA - whether alone or in combination with SR - as first-line MT seems to provide more rapid and successful reperfusion when compared with SR.