Whether dynamic changes of metabolic syndrome (MetS) affects the subsequent laryngeal cancer occurrence remains unknown. This study investigated the effects of changes of MetS on the incidence of ...laryngeal cancer due to a lack of knowledge regarding the development of MetS in Korean population. A total of 6,757,048 individuals who received national health checkup in 2009 and follow-up health examination in 2011 were analyzed and followed up until 2018. MetS status included the following categories: MetS-chronic (n = 941,609), MetS-developed (n = 614,229), MetS-recovery (n = 455,835), and MetS-free (n = 4,745,375). With a median follow-up duration of 6.403 years, 1,350 subjects were newly diagnosed with laryngeal cancer. Compared to participants without MetS, adjusted hazard ratios (HR) (95% confidence interval) for those with MetS were 1.320 (1.17-1.489) for laryngeal cancer. The HR of laryngeal cancer was found to be increased with increasing number of MetS components. The MetS-developed group had a significantly higher risk of laryngeal cancer than the MetS-free group (HR: 1.296; 95% CI: 1.093-1.537). The MetS-recovery group within two years also had an increased risk of laryngeal cancer compared with the MetS-free group (HR: 1.220; 95% CI: 1.008-1.476). Among MetS components, abdominal obesity had the highest risk of laryngeal cancer (HR: 1.374; 95% CI: 1.123-1.681). Changes in MetS status were associated with the risk of laryngeal cancer. Results of this study have implications for etiological investigations and prevention strategies.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Low-grade mitochondrial stress can promote health and longevity, a phenomenon termed mitohormesis. Here, we demonstrate the opposing metabolic effects of low-level and high-level mitochondrial ...ribosomal (mitoribosomal) stress in hypothalamic proopiomelanocortin (POMC) neurons. POMC neuron-specific severe mitoribosomal stress due to Crif1 homodeficiency causes obesity in mice. By contrast, mild mitoribosomal stress caused by Crif1 heterodeficiency in POMC neurons leads to high-turnover metabolism and resistance to obesity. These metabolic benefits are mediated by enhanced thermogenesis and mitochondrial unfolded protein responses (UPRmt) in distal adipose tissues. In POMC neurons, partial Crif1 deficiency increases the expression of β-endorphin (β-END) and mitochondrial DNA-encoded peptide MOTS-c. Central administration of MOTS-c or β-END recapitulates the adipose phenotype of Crif1 heterodeficient mice, suggesting these factors as potential mediators. Consistently, regular running exercise at moderate intensity stimulates hypothalamic MOTS-c/β-END expression and induces adipose tissue UPRmt and thermogenesis. Our findings indicate that POMC neuronal mitohormesis may underlie exercise-induced high-turnover metabolism.
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•Mild mitoribosomal stress in POMC neurons leads to a high metabolic turnover•POMC mitoribosomal stress activates thermogenesis and UPRmt in the adipose tissues•mtDNA-derived MOTS-c coordinates mitoribosomal stress response in POMC neurons•Regular exercise stimulates thermogenesis via hypothalamic neuronal mitohormesis
Kang et al. demonstrate that high-level mitochondrial stress in POMC-producing neurons causes severe obesity. In contrast, low-level mitochondrial stress in the same neurons enhances thermogenesis in the adipose tissue and protects against obesity via interorgan mitochondrial stress responses between the brain and adipose tissue.
Introduction. Mucosal margins exhibit a mean shrinkage of 30−40% after resection of oral and oropharyngeal cancers, and an adequate in situ surgical margin frequently results in a pathological close ...margin. However, the impact on prognosis remains unclear. We investigated the impact of a pathological close margin on disease-free survival (DFS) and overall survival (OS). Methods. We retrospectively reviewed the clinicopathological data of 418 patients diagnosed with squamous cell carcinomas of the oral cavity or oropharynx who underwent initial surgery (with curative intent) at our institute between 2010 and 2016. Results. Of the total population, the pathological marginal status of 290 (69.4%) patients was reported as clear (>5 mm), 61 (14.6%) as close (>1 mm, ≤5 mm), and 67 (16.0%) as positive (≤1 mm). The 5-year DFSs were 79.3%, 65.1%, and 52% in patients in the negative margin (group 1), close margin (group 2), and positive margin (group 3) groups, respectively. The difference between groups 1 and 2 was not significant (p = 0.213) but the difference between groups 2 and 3 was (p = 0.034). The 5-year OSs were 79.4%, 84%, and 52.3% in groups 1, 2, and 3, respectively. The difference between groups 1 and 2 was not significant (p = 0.824) but the difference between groups 2 and 3 was (p = 0.001). In multivariate analysis, older age, advanced T stage, and a positive margin were independently prognostic of the 5-year DFS and OS. Conclusion. In conclusion, the OS of patients with close margins was no different than that of others when appropriate postoperative adjuvant and/or salvage treatment were/was prescribed. However, we could not determine the impact of close margins on locoregional recurrence given various biases in our study setting. A future prospective study is needed.
Obesity is a metabolic disease characterized by an increased risk of type 2 diabetes, hypertension, and cardiovascular disease. We have previously reported that compounds isolated from brown alga,
...(ST;
(Mertens ex Roth) Kuntze), inhibit adipogenesis in 3T3-L1 cells. However, the in vivo anti-obesity effects of these compounds have not been previously reported. Therefore, the objective of this study was to determine the effects of ST on weight loss, fat accumulation, as well as risk factors for type 2 diabetes and cardiovascular disease in high-fat diet (HFD)-induced obese mice. ST treatment significantly decreased body weight and fat accumulation in HFD-induced obese mice, while reducing insulin and factors related to cardiovascular diseases (triglyceride and total cholesterol) in serum. ST-induced downregulation of PPARγ in white adipose tissue, and upregulation of the thermogenic genes,
and
, in brown adipose tissue was also observed. In addition, oral administration of ST reduced the occurrence of fatty liver, as well as the amount of white adipose tissue in HFD mice. Cumulatively, these results suggest that ST exerts anti-obesity effects and may serve as a potential anti-obesity therapeutic agent.
G protein-coupled receptors (GPCRs) are a diverse family of cell surface receptors implicated in various physiological functions, making them common targets for approved drugs. Many GPCRs are ...abnormally activated in cancers and have emerged as therapeutic targets for cancer. Neuropeptide FF receptor 2 (NPFFR2) is a GPCR that helps regulate pain and modulates the opioid system; however, its function remains unknown in cancers. Here, we found that NPFFR2 is significantly up-regulated in liver cancer and its expression is related to poor prognosis. Silencing of NPFFR2 reduced the malignancy of liver cancer cells by decreasing cell survival, invasion, and migration, while its overexpression increased invasion, migration, and anchorage-independent cell growth. Moreover, we found that the malignant function of NPFFR2 depends on RhoA and YAP signaling. Inhibition of Rho kinase activity completely restored the phenotypes induced by NPFFR2, and RhoA/F-Actin/YAP signaling was controlled by NPFFR2. These findings demonstrate that NPFFR2 may be a potential target for the treatment of hepatocellular carcinoma.
Korean isolates of the Mycobacterium chelonae-Mycobacterium abscessus group, which had been isolated from two different hospitals in South Korea, were identified by PCR restriction analysis (PRA) and ...comparative sequence analysis of 16S rRNA genes, rpoB, and hsp65 to evaluate the proportion of four closely related species (M. chelonae, M. abscessus, M. massiliense, and M. bolletii). Of the 144 rapidly growing mycobacterial strains tested, 127 strains (88.2%) belonged to the M. chelonae-M. abscessus group. In this group, M. chelonae, M. abscessus, M. massiliense, and M. bolletii accounted for 0.8% (n = 1), 51.2% (n = 65), 46.5% (n = 59), and 1.6% (n = 2), respectively. Two isolates which showed discordant results, M. massiliense by rpoB sequence analysis and M. abscessus by hsp65 sequence analysis, were finally identified as M. massiliense based on the additional analysis of sodA and the 16S-23S internal transcribed spacer. M. abscessus group I isolates previously identified by hsp65 PRA were all found to be M. abscessus, whereas group II isolates were further identified as M. massiliense or M. bolletii by sequencing of rpoB and hsp65. Smooth, rough, or mixed colonies of both M. abscessus and M. massiliense isolates were observed. M. massiliense strains that were highly resistant to clarithromycin had a point mutation at the adenine at position 2058 (A₂₀₅₈) or 2059 (A₂₀₅₉) in the peptidyltransferase region of the 23S rRNA gene.
Lipid droplets (LDs) are key subcellular organelles for regulating lipid metabolism. Although several subcellular organelles participate in lipid metabolism, it remains elusive whether physical ...contacts between subcellular organelles and LDs might be involved in lipolysis upon nutritional deprivation. Here, we demonstrate that peroxisomes and peroxisomal protein PEX5 mediate fasting-induced lipolysis by stimulating adipose triglyceride lipase (ATGL) translocation onto LDs. During fasting, physical contacts between peroxisomes and LDs are increased by KIFC3-dependent movement of peroxisomes toward LDs, which facilitates spatial translocations of ATGL onto LDs. In addition, PEX5 could escort ATGL to contact points between peroxisomes and LDs in the presence of fasting cues. Moreover, in adipocyte-specific PEX5-knockout mice, the recruitment of ATGL onto LDs was defective and fasting-induced lipolysis is attenuated. Collectively, these data suggest that physical contacts between peroxisomes and LDs are required for spatiotemporal translocation of ATGL, which is escorted by PEX5 upon fasting, to maintain energy homeostasis.
Despite advances in precision oncology, cancer remains a global public health issue. In this report, proof‐of‐principle evidence is presented that a cell‐penetrable peptide (ACP52C) dissociates ...transcription factor CP2c complexes and induces apoptosis in most CP2c oncogene‐addicted cancer cells through transcription activity‐independent mechanisms. CP2cs dissociated from complexes directly interact with and degrade YY1, leading to apoptosis via the MDM2‐p53 pathway. The liberated CP2cs also inhibit TDP2, causing intrinsic genome‐wide DNA strand breaks and subsequent catastrophic DNA damage responses. These two mechanisms are independent of cancer driver mutations but are hindered by high MDM2 p60 expression. However, resistance to ACP52C mediated by MDM2 p60 can be sensitized by CASP2 inhibition. Additionally, derivatives of ACP52C conjugated with fatty acid alone or with a CASP2 inhibiting peptide show improved pharmacokinetics and reduced cancer burden, even in ACP52C‐resistant cancers. This study enhances the understanding of ACP52C‐induced cancer‐specific apoptosis induction and supports the use of ACP52C in anticancer drug development.
Cancer‐specific synthetic lethality is demonstrated by targeting transcription factor CP2c with ACP52C, a cell‐penetrant peptide. ACP52C induces apoptosis, genomic instability, and G2/M arrest in most cancers, regardless of their driver mutations. Resistance in MDM2 p60‐expressing cells is overcome with CASP2 inhibition. Improved derivatives of ACP52C reduce cancer burden, supporting pan‐anticancer drug development.
Neuroinflammation is associated with neurodegenerative diseases, including Alzheimer's disease (AD). Thus, modulating the neuroinflammatory response represents a potential therapeutic strategy for ...treating neurodegenerative diseases. Several recent studies have shown that dopamine (DA) and its receptors are expressed in immune cells and are involved in the neuroinflammatory response. Thus, we recently developed and synthesized a non-self-polymerizing analog of DA (CA140) and examined the effect of CA140 on neuroinflammation.
To determine the effects of CA140 on the neuroinflammatory response, BV2 microglial cells were pretreated with lipopolysaccharide (LPS, 1 μg/mL), followed by treatment with CA140 (10 μM) and analysis by reverse transcription-polymerase chain reaction (RT-PCR). To examine whether CA140 alters the neuroinflammatory response in vivo, wild-type mice were injected with both LPS (10 mg/kg, intraperitoneally (i.p.)) and CA140 (30 mg/kg, i.p.), and immunohistochemistry was performed. In addition, familial AD (5xFAD) mice were injected with CA140 or vehicle daily for 2 weeks and examined for microglial and astrocyte activation.
Pre- or post-treatment with CA140 differentially regulated proinflammatory responses in LPS-stimulated microglia and astrocytes. Interestingly, CA140 regulated D1R levels to alter LPS-induced proinflammatory responses. CA140 significantly downregulated LPS-induced phosphorylation of ERK and STAT3 in BV2 microglia cells. In addition, CA140-injected wild-type mice exhibited significantly decreased LPS-induced microglial and astrocyte activation. Moreover, CA140-injected 5xFAD mice exhibited significantly reduced microglial and astrocyte activation.
CA140 may be beneficial for preventing and treating neuroinflammatory-related diseases, including AD.
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