Analysis of predictors of fever after aortic valve replacement: Diabetic patients are less likely to develop fever after aortic valve replacement, a single-centre retrospective study.

BACKGROUND: Postoperative temperature dysregulation affects the length of hospital stay and prognosis. This study evaluated the factors that influence the occurrence of fever in patients after aortic valve replacement surgery. METHODS: Eighty-seven consecutive patients who underwent aortic valve replacement surgery were included. Patients' age, sex and body mass index; presence of diabetes mellitus; operation time; blood loss; blood transfusion volume; preoperative and postoperative laboratory findings; presence or absence of oral function management; and fever >38°C were retrospectively analysed through univariate and multiple logistic regression analyses. RESULTS: Among the variables, only diabetes mellitus status was significantly associated with fever ⩾38°C. Postoperatively, patients with diabetes mellitus were significantly less likely to develop fever above 38°C and a fever rising to 38°C. CONCLUSIONS: This study shows that the presence of comorbid diabetes mellitus decreases the frequency of developing fever >38°C after aortic valve replacement surgery.

Integrative regulation of hLMR1 by dietary and genetic factors in nonalcoholic fatty liver disease and hyperlipidemia.

Long non-coding RNA (lncRNA) genes represent a large class of transcripts that are widely expressed across species. As most human lncRNAs are non-conserved, we recently employed a unique humanized liver mouse model to study lncRNAs expressed in human livers. We identified a human hepatocyte-specific lncRNA, hLMR1 (human lncRNA metabolic regulator 1), which is induced by feeding and promotes hepatic cholesterol synthesis. Recent genome-wide association studies (GWAS) found that several single-nucleotide polymorphisms (SNPs) from the hLMR1 gene locus are associated with blood lipids and markers of liver damage. These results suggest that dietary and genetic factors may regulate hLMR1 to affect disease progression. In this study, we first screened for nutritional/hormonal factors and found that hLMR1 was robustly induced by insulin/glucose in cultured human hepatocytes, and this induction is dependent on the transcription factor SREBP1. We then tested if GWAS SNPs genetically linked to hLMR1 could regulate hLMR1 expression. We found that DNA sequences flanking rs9653945, a SNP from the last exon of the hLMR1 gene, functions as an enhancer that can be robustly activated by SREBP1c depending on the presence of rs9653945 major allele (G). We further performed CRISPR base editing in human HepG2 cells and found that rs9653945 major (G) to minor (A) allele modification resulted in blunted insulin/glucose-induced expression of hLMR1. Finally, we performed genotyping and gene expression analyses using a published human NAFLD RNA-seq dataset and found that individuals homozygous for rs9653945-G have a higher expression of hLMR1 and risk of NAFLD. Taken together, our data support a model that rs9653945-G predisposes individuals to insulin/glucose-induced hLMR1, contributing to the development of hyperlipidemia and NAFLD.

Predictors of Occult Metastasis and Prognostic Factors in Patients with cN0 Oral Cancer Who Underwent Elective Neck Dissection.

Elective neck dissection (END) is recommended for the management of patients with oral squamous cell carcinoma (OSCC) because of the risk of occult metastasis (OM). We hypothesized that some factors predict poor prognosis regardless of a cN0 END. This study aimed to investigate the predictors of OM and prognostic factors in patients with cN0 OSCC who underwent supraomohyoid neck dissection (SOHND). A retrospective cohort study design was created and implemented. The primary predictive variables in this study were OM and risk factors for poor prognosis after SOHND. A Cox proportional hazard model was used to adjust for the effects of potential confounders on the risk factors for poor prognoses. Among 86 patients with OSCC, OMs were observed in 9 (10.5%). The neutrophil-to-lymphocyte ratio (NLR) and vascular invasion are good markers for detecting OM. A Cox multivariable analysis identified two independent predictors of overall survival: pathologic node (pN) and laterality of END. An independent predictive factor for disease-free survival, the surgical margin, was also identified in this study. According to the pN classification, pN1 patients had a worse survival rate than pN2 patients. Therefore, in the case of pN1, regardless of being cN0, additional adjuvant therapy may be necessary.

Involvement of submandibular gland in oral squamous cell carcinoma.

BACKGROUND: The submandibular gland (SMG) is sacrificed during neck dissection in patients undergoing curative surgery for oral squamous cell carcinoma (OSCC). This may cause a decrease in the production of saliva and result in xerostomia. PURPOSE: This study aimed to determine the incidence, invasion patterns, risk factors, and prognosis of SMG involvement in OSCC. METHODS: The primary predictor variable in this study was SMG involvement, and the secondary predictor was prognosis. MAIN FINDINGS: The primary outcome variables were patient characteristics and pathological results for extranodal extension (ENE), perineural invasion (PNI), and pN stage. Four out of 173 patients (2.23 %) showed SMG involvement. Of these cases, one (25 %) was from the primary lesion and three (75 %) were from the metastatic neck lymph nodes (LNs). The primary lesion was located on the lower gingiva, and the other three were from level-Ib LNs with ENE. The pathological PNI was observed in three of the four patients, and ENE was observed in three of the four patients. Preoperative CT and MR revealed SMG invasion and contact in two patients. There were significant differences in the ENE and pN stages between patients with and without SMG involvement (P<0.05). There was a significant difference in the overall survival between patients with (25.0 %) and without (71.5 %) SMG involvement (P = 0.011). CONCLUSIONS: SMG involvement was associated with ENE, pN stage, and poor prognosis.

p62 Is a Potential Biomarker for Risk of Malignant Transformation of Oral Potentially Malignant Disorders (OPMDs).

To determine the intracellular behavior of p62, a marker of selective autophagy, in oral potentially malignant disorders (OPMDs). This retrospective study includes 70 patients who underwent biopsy or surgical resection and were definitively diagnosed with OPMDs. Immunohistochemical staining for p62, XPO1, p53, and ki67 was performed on all samples and positive cell occupancy was calculated. We statistically investigated the correlation between protein expression in OPMDs and the association between malignant transformation, clinicopathological characteristics, and occupancy. ki67 expression was negatively correlated with p62 expression in the nucleus (p < 0.01) and positively correlated with p62 expression in the cytoplasm (p < 0.01). For malignant transformation, the expression of p62 in the nucleus (p = 0.03) was significantly lower in malignant transformation cases, whereas the expression of p62 in the cytoplasm (p = 0.03) and the aggregation expression (p < 0.01) were significantly higher. Our results suggest that the function of p62 is altered by its subcellular localization. In addition, defects in selective autophagy occur in cases of malignant transformation, suggesting that p62 is a potential biomarker of the risk of malignant transformation of OPMDs.

Efficacy of redox nanoparticles for improving survival of transplanted cells in a mouse model of ischemic stroke.

The success of cell transplantation therapy for ischemic stroke is hindered by the low cell survival rate in poststroke brain, due in part to high free radical production and ensuing oxidative stress. We have developed redox nanoparticles to eliminate reactive oxygen species. In this study, we tested the protective efficacy of these redox nanoparticles in cell culture and a mouse model of ischemic stroke. Induced human dental pulp stem cells were subjected to oxygen-glucose deprivation and reoxygenation to recapitulate ischemia and reperfusion in the penumbra surrounding a cerebral infarct. Cell viability using WST-8 assay, apoptosis using TUNEL, free radicals using MitoSOX, and inflammatory cytokines using ELISA kit were measured in the presence and absence of redox nanoparticles after oxygen-glucose deprivation and reoxygenation. The scavenging activity of redox nanoparticles against reactive oxygen species was detected by electron spin resonance. Moreover, induced cells were transplanted intracerebrally into to the distal middle cerebral artery occlusion model with and without redox nanoparticles, and the survival rate measured. Cell viability was enhanced, while apoptosis, free radical generation, and inflammatory cytokine expression levels were reduced in cultures with redox nanoparticles. Further, reduced redox nanoparticles were detected in the cytoplasm, indicating free radical scavenging. Addition of redox nanoparticles also improved the survival rate of transplanted cells after 6 weeks in vivo. These redox nanoparticles may increase the applicability and success of induced stem cell therapy for ischemic stroke patents by promoting long-term survival.

Postoperative Deep Sedation after Microvascular Reconstructive Surgery for Oral Cancer Increases the Risk of Early Postoperative Pneumonia.

This study investigated the effect of postoperative deep sedation after oral cancer reconstructive surgery on the occurrence of early postoperative pneumonia and early postoperative delirium. We obtained medical records of 108 consecutive patients who underwent microvascular reconstructive surgery at Tsukuba University Hospital for oral cancer between January 2013 and December 2021. Forty-six of them woke soon after surgery. Ten of these forty-six patients were restless and required immediate sedation within 3 h after surgery. The comparison between sedation group and no sedation group revealed early postoperative pneumonia in the no sedation group; however, sedation was not related to early postoperative delirium. The preoperative albumin levels of patients with postoperative pneumonia were significantly different (p = 0.03) than those of patients without postoperative pneumonia. The performance status (p = 0.02), preoperative albumin level (p = 0.02), and age 75 years or older (p = 0.02) were significantly associated with postoperative delirium. Restless patients and those who could not be sedated experienced delirium and pneumonia. The risk of pneumonia was increased for patients who were difficult to sedate.

Prognostic prediction using maximum standardized uptake value ratio of lymph node-to-primary tumor in preoperative PET-CT for oral squamous cell carcinoma.

This study aimed to calculate the ratio of maximum standardized uptake values of cervical lymph nodes to maximum standardized uptake values of primary tumors measured by preoperative fluorodeoxyglucose positron-emission tomography in oral cancer patients, and to retrospectively examine the prognostic association and evaluate whether it could be a prognostic factor. We retrospectively examined consecutive Japanese patients diagnosed with oral squamous cell carcinoma who underwent oral cancer resection and cervical dissection between January 2014 and December 2018. The study included 52 patients aged 39-89 years (median age 66.5 years), excluding non-cervical dissection surgery and/or non-underwent preoperative positron-emission tomography. The maximum standardized uptake value of the cervical lymph nodes and primary tumor was measured, and the ratio of maximum standardized uptake values of the lymph nodes to that of the primary tumor was calculated. The median follow-up of 52 patients was 1,465 days (198-2,553 days), and overall survival was significantly worse in patients with a high lymph node-to-tumor standardized uptake values ratio (>0.4739) (5 years, 58.8% vs. 88.2%; P<0.05). Pretreatment lymph node-to-tumor standardized uptake values ratio can be easily calculated, and as a predictor of prognosis, it may be of assistance when considering the treatment strategy for oral cancer.

Anatomical Variant of Spinal Accessory Nerve Passing through Fenestrated Internal Jugular Vein.

Neck dissection (ND) is a major surgery for head and neck cancer. Currently, some or all of the spinal accessory nerve (SAN), sternocleidomastoid muscle, and internal jugular vein (IJV) are aggressively preserved during ND to reduce postoperative complications. Since the anatomical relationship between the SAN and IJV has several variations, knowledge of these variations is necessary to avoid iatrogenic damage. In the present case, the SAN was observed to pass through the fenestrated IJV at the level of the posterior belly of the digastric muscle during ND in a patient with squamous cell carcinoma of the mandible. Although the anatomical structure of the SAN and IJV is rare, surgeons must be aware of this anatomical variation.

Lip Epidermoid Cyst Caused by a Piercing: A Report of a Rare Case.

We report the case of a lip epidermoid cyst, caused by piercing in a 23-year-old Japanese woman. She had an exophytic lesion in the lower lip associated with the piercing which was initially diagnosed as a mucous retention cyst. The lesion was resected under local anesthesia, and pathological examination revealed an epidermoid cyst, likely caused by piercings. Piercing-induced epidermoid cysts frequently occur in the tragus. There have been no reports of piercing-induced epidermoid cysts developing in the oral cavity. To our knowledge, this is the first report of a lip epidermal cyst caused by piercings. Six months have passed since the operation, and it has not recurred.

Inducing substances for chondrogenic differentiation of dental pulp stem cells in the conditioned medium of a novel chordoma cell line.

We successfully established a chordoma cell line, designated TSK-CHO1, derived from the clival chordoma. Currently, there is only one skull base chordoma cell line, UM-chor1, freely available to researchers. The established TSK-CHO1 cells were neoplastic, exhibited pleomorphic features, and secreted brachyury, as revealed by immunocytochemical staining or ELISA of conditioned medium (CM). Cells also secreted SOX9, which enhanced brachyury production. The CM of TSK-CHO1 cells promoted the production of hyaluronic acid and type II collagen during differentiation of human dental pulp stem cells (DPSCs) into fibrocartilage cells. Culture of DPSC pellets in a growth medium supplemented with 10% CM of TSK-CHO1 cells for 2 weeks resulted in the induction of fibrocartilage tissue under normoxic conditions. Brachyury produced by TSK-CHO1 cells promoted the production of collagen type II, peculiar to cartilage, in a dose-dependent manner. The newly established skull base chordoma cell line, TSK-CHO1, is expected to be used for elucidating the pathogenesis of skull base chordoma and for investigating the mechanism underlying the production of fibrocartilage.

Transplanted neural lineage cells derived from dental pulp stem cells promote peripheral nerve regeneration.

Cell therapy for peripheral nerve injury is a promising strategy as regenerative medicine that restores neurological function. However, challenges remain in producing suitable and sufficient amounts of autologous cells for promoting nerve regeneration. This study aimed to identify the characteristics of neural lineage cells (NLCs) differentiated from dental pulp stem cells (DPSCs) and reveal their effect on functional recovery and nerve regeneration after cell transplantation into an immunodeficient rat using a nerve guide conduit. Here we report a protocol of neural induction in monolayer culture and characterize NLCs in vitro. Furthermore, NLCs were transplanted into an immunodeficient rat model with a 10-mm sciatic nerve defect, and cell survival and differentiation were investigated in vivo. Outcomes of nerve regeneration were also assessed using the remyelinated axon numbers, myelin sheath thickness, electrophysiological activities, and gastrocnemius muscle mass. NLCs comprised neuronal, astrocyte, oligodendrocyte, and neural crest lineage cells. NLCs enhanced the activities of endothelial cells, Schwann cells, and neurons in a paracrine-dependent manner in vitro. At 2 weeks post-transplantation, numerous transplanted NLCs differentiated into platelet-derived growth factor receptor alpha (PDGFRα) + oligodendrocyte progenitor cells (OPCs) and a few PDGFRα + /p75 neurotrophin receptor + Schwann cell-like cells derived from OPCs were observed. At 12 weeks post-transplantation, human Schwann cell-like cells survived, and axon growth, remyelination, electrophysiological activities, and muscle atrophy were improved. This study demonstrates the broad application of our protocol of neural induction of DPSCs and portrays the efficacy of transplantation of NLCs derived from human DPSCs as a promising strategy for peripheral nerve regeneration.

Nasal molding prevents relapse of nasal deformity after primary rhinoplasty in patients with unilateral complete cleft lip: An outcomes-based comparative study of palatal plate alone versus nasoalveolar molding.

OBJECTIVES: In recent years, many studies have reported that the presurgical nasoalveolar molding method improves the nose morphology; however, the reason for its effectiveness after surgery has never been understood. We evaluated the effect of nasoalveolar molding by comparing it with a passive orthopedic method without a nasal stent and focusing on the nostril morphology after primary cheiloplasty using various measurement methods. We then analyzed the essential factors. MATERIALS AND METHODS: The patients involved were 31 infants with unilateral complete cleft lip and palate treated with primary cheiloplasty at the University of Tsukuba Hospital from 2004 to 2011. Of the 31 infants, 16 received nasoalveolar molding treatment and 15 received passive orthopedic treatment as controls. Photographic facial measurements were performed for all patients immediately and 7 months after primary cheiloplasty. The esthetics of the nostrils were assessed according to the left-right nostril symmetry, as measured by the Hausdorff distance, area ratio, perimeter ratio, and aspect a/u (the aspect ratio of the affected side)/(the aspect ratio of the unaffected side) ratio. In addition, the inclination of the nasal ridge was assessed using anthropometric measurements (Grc-Grn∠midline and midline∠columellar axis). RESULTS: The area ratio, perimeter ratio, and Grc-Grn∠midline were significantly greater in the nasoalveolar molding group immediately after surgery (p = 0.00062, 0.016, and 0.048, respectively) than in the control group. However, the Hausdorff distance and aspect a/u ratio were more favorable (p = 0.0018 and 0.0039, respectively) in the nasoalveolar molding group after 7 months. CONCLUSIONS: The results of our study suggested that using nasoalveolar molding as a presurgical orthopedic treatment could improve the shape of the nasal cartilage with surgeon's corrections.

Induced Neural Cells from Human Dental Pulp Ameliorate Functional Recovery in a Murine Model of Cerebral Infarction.

Human mesenchymal stem cells are a promising cell source for the treatment of stroke. Their primary mechanism of action occurs via neuroprotective effects by trophic factors, anti-inflammatory effects, and immunomodulation. However, the regeneration of damaged neuronal networks by cell transplantation remains challenging. We hypothesized that cells induced to neural lineages would fit the niche, replace the lesion, and be more effective in improving symptoms compared with stem cells themselves. We investigated the characteristics of induced neural cells from human dental pulp tissue and compared the transplantation effects between these induced neural cells and uninduced dental pulp stem cells. Induced neural cells or dental pulp stem cells were intracerebrally transplanted 5 days after cerebral infarction induced by permanent middle cerebral artery occlusion in immunodeficient mice. Effects on functional recovery were also assessed through behavior testing. We used immunohistochemistry and neuron tracing to analyze the differentiation, axonal extension, and connectivity of transplanted cells to the host's neural circuit. Transplantation of induced neural cells from human dental pulp ameliorated functional recovery after cerebral infarction compared with dental pulp stem cells. The induced neural cells comprised both neurons and glia and expressed functional voltage, and they were more related to neurogenesis in terms of transcriptomics. Induced neural cells had a higher viability than did dental pulp stem cells in hypoxic culture. We showed that induced neural cells from dental pulp tissue offer a novel therapeutic approach for recovery after cerebral infarction.

MicroRNA 142-5p promotes tumor growth in oral squamous cell carcinoma via the PI3K/AKT pathway by regulating PTEN.

MicroRNAs (miRNAs) play an important role in carcinogenesis and cancer progression. The purpose of this study was to identify miRNAs associated with carcinoma function in OSCC and to investigate the potential role of the specific miRNAs. First, a comprehensive microarray analysis was performed, and miR-142-5p was identified as a candidate miRNA involved in OSCC. miR-142-5p has been reported to show high expression levels in cancer patients and to be involved in tumor growth and metastasis. However, the expression and function of miR-142-5p in oral squamous cell carcinoma (OSCC) are not fully characterized. We evaluated miR-142-5p expression in both OSCC-derived cell lines and primary OSCC tissues and performed functional analysis of miR-142-5p in OSCC-derived cell lines using mimics and inhibitors. miR-142-5p expression was up-regulated in OSCC tissues and OSCC cell lines. Overexpression of miR-142-5p significantly promoted the proliferation and invasion of OSCC cells. Bioinformatics analysis was performed using TargetScan to predict potential target sites that match the seed region of miR-142-5p. Phosphatase and tensin homolog deleted on chromo-some 10 (PTEN) was identified as a potential target and selected for further analysis. PTEN expression levels were down-regulated and AKT expression levels were up-regulated in miR-142-5p-overexpressing cells. We have shown that miR-142-5p targets the PTEN gene and is involved in cancer progression. Our results suggest that miR-142-5p is involved in the progression of OSCC by controlling the phosphatidylinositol 3-kinase (PI3K)/AKT pathway by targeting the PTEN gene. Our findings suggest that miR-142-5p may be a new target for the treatment of OSCC.

Neuronal XRN1 is required for maintenance of whole-body metabolic homeostasis.

Control of mRNA stability and degradation is essential for appropriate gene expression, and its dysregulation causes various disorders, including cancer, neurodegenerative diseases, diabetes, and obesity. The 5'-3' exoribonuclease XRN1 executes the last step of RNA decay, but its physiological impact is not well understood. To address this, forebrain-specific Xrn1 conditional knockout mice (Xrn1-cKO) were generated, as Xrn1 null mice were embryonic lethal. Xrn1-cKO mice exhibited obesity with leptin resistance, hyperglycemia, hyperphagia, and decreased energy expenditure. Obesity resulted from dysregulated communication between the central nervous system and peripheral tissues. Moreover, expression of mRNAs encoding proteins that regulate appetite and energy expenditure was dysregulated in the hypothalamus of Xrn1-cKO mice. Therefore, we propose that XRN1 function in the hypothalamus is critical for maintenance of metabolic homeostasis.

The CCR4-NOT complex maintains liver homeostasis through mRNA deadenylation.

The biological significance of deadenylation in global gene expression is not fully understood. Here, we show that the CCR4-NOT deadenylase complex maintains expression of mRNAs, such as those encoding transcription factors, cell cycle regulators, DNA damage response-related proteins, and metabolic enzymes, at appropriate levels in the liver. Liver-specific disruption of Cnot1, encoding a scaffold subunit of the CCR4-NOT complex, leads to increased levels of mRNAs for transcription factors, cell cycle regulators, and DNA damage response-related proteins because of reduced deadenylation and stabilization of these mRNAs. CNOT1 suppression also results in an increase of immature, unspliced mRNAs (pre-mRNAs) for apoptosis-related and inflammation-related genes and promotes RNA polymerase II loading on their promoter regions. In contrast, mRNAs encoding metabolic enzymes become less abundant, concomitant with decreased levels of these pre-mRNAs. Lethal hepatitis develops concomitantly with abnormal mRNA expression. Mechanistically, the CCR4-NOT complex targets and destabilizes mRNAs mainly through its association with Argonaute 2 (AGO2) and butyrate response factor 1 (BRF1) in the liver. Therefore, the CCR4-NOT complex contributes to liver homeostasis by modulating the liver transcriptome through mRNA deadenylation.

A small number of residual teeth after the mandibular resection of oral cancer is associated with titanium reconstruction plate exposure.

Objective: Reconstruction plates are used to treat patients with a segmental mandibular defect after oral cancer surgery. Reconstruction plate failure analysis has rarely focused on occlusion, which conducts a mechanical force to the mandible and the plate. To determine the prognostic factors, we retrospectively evaluated patients who underwent reconstruction of a mandibular segmental defect with a reconstruction plate and assessed the number of residual paired teeth. Material and Methods: From among 390 patients with oral cancer who visited University of Tsukuba Hospital (Tsukuba, Japan) between 2007 and 2017, we selected and analyzed the data of 37 patients who underwent segmental resection of the mandible and reconstruction with reconstruction plates. Prognostic factors evaluated were patient age, sex, TNM classification, plate manufacturer, treatment with radiotherapy or chemotherapy, whether the patient had diabetes or smoked, and whether the patient had a small number of residual paired teeth, plate length, and use of a fibular-free flap. Among these 37 patients, eight reconstruction plates had intraoral or extraoral exposure and were removed in 5 years. Results: Kaplan-Meier and log-rank analyses revealed that the prognosis for the 5-year plate exposure-free rate was significantly poorer for patients with a small number of residual teeth than for patients with no teeth or those with a large number of residual teeth (.01). Univariate Cox regression analysis revealed that a small number of residual teeth was a significant prognostic factor in the loss of a reconstruction plate (hazard ratio: 5.63; 95% confidence interval [1.10, 25.85]; .04). Conclusions: A small number of residual teeth after the segmental resection of oral cancer is significantly involved in reconstruction plate survival and may be important in predicting reconstruction plate prognosis.

The CCR4-NOT Deadenylase Complex Maintains Adipocyte Identity.

Shortening of poly(A) tails triggers mRNA degradation; hence, mRNA deadenylation regulates many biological events. In the present study, we generated mice lacking the Cnot1 gene, which encodes an essential scaffold subunit of the CCR4-NOT deadenylase complex in adipose tissues (Cnot1-AKO mice) and we examined the role of CCR4-NOT in adipocyte function. Cnot1-AKO mice showed reduced masses of white adipose tissue (WAT) and brown adipose tissue (BAT), indicating abnormal organization and function of those tissues. Indeed, Cnot1-AKO mice showed hyperinsulinemia, hyperglycemia, insulin resistance, and glucose intolerance and they could not maintain a normal body temperature during cold exposure. Muscle-like fibrous material appeared in both WAT and BAT of Cnot1-AKO mice, suggesting the acquisition of non-adipose tissue characteristics. Gene expression analysis using RNA-sequencing (RNA-seq) showed that the levels of adipose tissue-related mRNAs, including those of metabolic genes, decreased, whereas the levels of inflammatory response-related mRNAs increased. These data suggest that the CCR4-NOT complex ensures proper adipose tissue function by maintaining adipocyte-specific mRNAs at appropriate levels and by simultaneously suppressing mRNAs that would impair adipocyte function if overexpressed.

The CCR4-NOT deadenylase activity contributes to generation of induced pluripotent stem cells.

Somatic cells can be reprogrammed as induced pluripotent stem cells (iPSCs) by introduction of the transcription factors, OCT3/4, KLF4, SOX2, and c-MYC. The CCR4-NOT complex is the major deadenylase in eukaryotes. Its subunits Cnot1, Cnot2, and Cnot3 maintain pluripotency and self-renewal of mouse and human embryonic stem (ES) cells and contribute to the transition from partial to full iPSCs. However, little is known about how the CCR4-NOT complex post-transcriptionally regulates the reprogramming process. Here, we show that the CCR4-NOT deadenylase subunits Cnot6, Cnot6l, Cnot7, and Cnot8, participate in regulating iPSC generation. Cnot1 knockdown suppresses expression levels of Cnot6, Cnot6l, Cnot7, and Cnot8 in mouse embryonic fibroblasts (MEFs) and decreases the number of alkaline phosphatase (ALP)-positive colonies after iPSC induction. Intriguingly, Cnot1 depletion allows Eomes and p21 mRNAs to persist, increasing their expression levels. Both mRNAs have longer poly(A) tails in Cnot1-depleted cells. Conversely, forced expression of a combination of Cnot6, Cnot6l, Cnot7, and Cnot8 increases the number of ALP-positive colonies after iPSC induction and decreases expression levels of Eomes and p21 mRNAs. Based on these observations, we propose that the CCR4-NOT deadenylase activity contributes to iPSC induction.