Pulmonary Tuberculosis Following Immune Checkpoint Inhibitor Treatment for Recurrent Maxillary Squamous Cell Carcinoma.

Immune checkpoint inhibitors (ICIs) like nivolumab and pembrolizumab are effective treatments for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, they can lead to immune-related adverse events (irAEs) and tuberculosis (TB) reactivation. We present a case of a 79-year-old male with recurrent maxillary squamous cell carcinoma treated with pembrolizumab, cisplatin, and 5-fluorouracil. The patient developed a fever, and pulmonary TB development was confirmed. Prolonged TB treatment was required, and ICI treatment was discontinued. The patient ultimately opted for palliative care due to aggressive tumor growth. TB development during ICI treatment is a rare but important concern, especially in TB-endemic areas. Vigilant monitoring and screening might be essential to manage this risk in cancer patients with R/M SCCHN receiving ICIs.

Prognostic effect of programmed cell death ligand 1/programmed cell death 1 expression in cancer stem cells of human oral squamous cell carcinoma.

The relationship between cancer stem cells (CSCs) in oral squamous cell carcinoma (OSCC) and programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) remains unclear. Therefore, the present study aimed to clarify the association between the CD44v3high/CD24low immunophenotype of CSCs in OSCC and PD-L1/PD-1 co-expression, and to assess the prognostic effect of CSCs in terms of immune checkpoint molecules. Formalin-fixed, paraffin-embedded tissue samples and clinicopathological data from 168 patients with OSCC were retrospectively retrieved. Immunohistochemical staining and reverse transcription quantitative polymerase chain reaction were applied to a tissue microarray of the invasive front of each case. Semi-automated cell counting was used to assess CD44v3, CD24, PD-L1 and PD-1 expression by immunohistochemistry (IHC) using a digital image analysis program. Associations between immunological markers and clinicopathological variables were estimated. Patients with the CSC immunophenotype CD44v3high/CD24low, and patients with a high PD-L1/PD-1-positive cell density in the tumor parenchyma and stroma had significantly lower survival rates. Furthermore, patients with the CSC immunophenotype (CD44v3high/CD24low) and high PD-L1/PD-1 co-expression had even lower survival rates (P<0.01, log-rank test). Notably, there was a positive correlation between CD44v3 and PD-L1 expression (τ=0.1096, P=0.0366, Kendall rank correlation coefficient) and a negative correlation between CD24 and PD-1 expression (τ=-0.1387, P=0.0089, Kendall rank correlation coefficient). Additionally, the high CD44v3 expression group, as determined by IHC, exhibited significantly decreased expression of U2 small nuclear RNA auxiliary factor 1 (U2AF1) at the mRNA level compared with that in the low CD44v3 expression group (P<0.001, Mann-Whitney U test), and U2AF1 and PD-L1 mRNA expression exhibited a significant negative correlation (τ=-0.3948, P<0.001, Kendall rank correlation coefficient). In conclusion, CSCs in OSCC may evade host immune mechanisms and maintain CSC stemness via PD-L1/PD-1 co-expression, resulting in unfavorable clinical outcomes.

Epiglottic Epidermoid Cyst: Cadaveric Case Report and Clinical-Surgical Applications.

An epidermoid cyst is lined with stratified squamous epithelium with a lumen filled with fluid, in most cases. Such cysts can occur anywhere in the body; however, they are rarely found on the epiglottis (0.54%). Herein, we describe to our knowledge, the first cadaveric case of a regular, circular, and soft mass extending out from the tip of the epiglottis with consistent histological characteristics of an epidermoid cyst. Epiglottic cysts are rare and mostly asymptomatic. However, through this case report, we aimed to highlight the clinical-surgical applications presented mainly when they grow large enough, to cause issues with ventilation or obstruct endotracheal tubes, thus interfering with airway management. Additionally, such cysts can affect swallowing or speaking.

Development of a new treatment for preterm birth complications using amniotic fluid stem cell therapy.

This paper describes the current status of studies and clinical trials on the use of mesenchymal stem cells (MSCs) and amniotic fluid stem cells (AFSCs) for complications of preterm birth (PTB), an urgent issue in the perinatal field. PTB is a serious challenge in clinical medicine that is increasing globally, and effective control of its complications is necessary for newborns' subsequent long life. Classical treatments are inadequate, and many patients have PTB complications. A growing body of evidence provided by translational medicine and others indicates that MSCs, and among them, the readily available AFSCs, may be useful in treating PTB complications. AFSCs are the only MSCs available prenatally and are known to be highly anti-inflammatory and tissue-protective and do not form tumors when transplanted. Furthermore, because they are derived from the amniotic fluid, a medical waste product, no ethical issues are involved. AFSCs are an ideal cell resource for MSC therapy in neonates. This paper targets the brain, lungs, and intestines, which are the vital organs most likely to be damaged by PTB complications. The evidence to date and future prospects with MSCs and AFSCs for these organs are described.

Prophylactic administration of human amniotic fluid stem cells suppresses inflammation-induced preterm birth via macrophage polarization.

Ascending inflammation from the vagina is a major cause of preterm birth. Currently, this condition-especially when uncontrolled-has no effective treatment. Human amniotic fluid stem cells (hAFSCs) are mesenchymal stem cells known to exert potent anti-inflammatory effects in animal models of perinatal diseases, such as periventricular leukomalacia, myelomeningocele, and neonatal sepsis. However, hAFSC therapy for inflammation-induced preterm birth has not been tested. In order to determine the therapeutic effect of hAFSC transplantation, we employed a preterm mouse model of ascending infection; this model was constructed by administering lipopolysaccharide to pregnant mice. We investigated the preterm birth rate and evaluated the inflammation of tissues, which is related to progressive infections, such as those involving the cervix, placenta, and lavage cells, using real-time qPCR. Further, we tracked the fluorescence of fluorescently labeled hAFSCs using an in vivo imaging system, and hAFSC aggregation was evaluated using immunohistochemistry analysis. We also investigated the presence of multiple types of peritoneal macrophages via flow cytometry analysis. Finally, we performed sphere culturing and co-culturing to determine the therapeutic effects of hAFSCs, such as their anti-inflammatory effects and their potential to alter macrophage polarization. We found that hAFSC administration to the peritoneal cavity significantly reduced inflammation-induced preterm birth in the mouse model. The treatment also significantly suppressed inflammation of the placenta and cervix. Transplanted hAFSCs may have aggregated with peritoneal macrophages, switching them from an inflammatory to an anti-inflammatory type. This property has been reported in vivo previously, but here, we examined the effect in vitro. Our findings support the hypothesis that hAFSCs suppress inflammation and reduce preterm birth by switching macrophage polarity. This study is the first to demonstrate that hAFSCs are effective in the treatment and prevention of inflammation-induced preterm birth.

Perioperative Management of a Patient With Tongue Cancer Who Developed Pneumomediastinum Following Tracheostomy Performed to Secure the Airway.

Prior to a scheduled operation for a 45-year-old male patient with tongue cancer, a tracheotomy performed under intravenous sedation to prevent asphyxia due to extensive bleeding resulted in pneumomediastinum and subcutaneous emphysema. The planned operations were postponed until reduction of the pneumomediastinum was confirmed. During operation, airway pressure was kept low to prevent tension pneumomediastinum along with a sufficient depth of anesthesia, controlled analgesia, and continuous administration of muscle relaxants. Postoperatively, sedation was used to avoid stress and complications with the vascular anastomosis site. In this case, air leakage into the soft tissues was one of the possible causes of the event associated with increased airway pressure. Although the incidence of such complications is relatively low, caution should be exercised after tracheostomy.

Coronary Spasm During Postoperative Sedation With Dexmedetomidine.

This is a case report of an 81-year-old woman who underwent tracheostomy, bilateral cervical dissection, partial tongue resection, radial forearm free flap reconstruction, and split-thickness skin grafting under general anesthesia. After successful surgery, she was moderately sedated postoperatively with intravenous dexmedetomidine (DEX) and fentanyl. The fentanyl was discontinued 5 hours postoperatively. Eight hours after the operation, an atrioventricular junctional rhythm, a 2-mm elevation of the ST segment, and biphasic T waves were detected in lead II that lasted approximately 3 minutes. Hypotension and bradycardia were observed simultaneously with the abnormal electrocardiogram. The next day, a cardiologist examined the patient and suggested that coronary spasm had occurred based on those findings. The transient coronary spasm was likely caused by a combination of various factors including surgical stress and altered autonomic function. However, it is possible that stimulation of α-2 adrenergic receptors induced by DEX may also be linked to the coronary vasospasm that occurred.

Human Amniotic Fluid Stem Cells Ameliorate Thioglycollate-Induced Peritonitis by Increasing Tregs in Mice.

Mesenchymal stem cells (MSCs) affect immune cells and exert anti-inflammatory effects. Human amniotic fluid stem cells (hAFSCs), a type of MSCs, have a high therapeutic effect in animal models of inflammation-related diseases. hAFSCs can be easily isolated and cultured from amniotic fluid, which is considered a medical waste. Hence, amniotic fluid can be a source of cells for MSC therapy of inflammatory diseases. However, the effect of hAFSCs on acquired immunity in vivo, especially on regulatory T cells, has not yet been fully elucidated. Therefore, in this study, we aimed to understand the effects of hAFSCs on acquired immunity, particularly on regulatory T cells. We showed that hAFSCs ameliorated the thioglycollate-induced inflammation by forming aggregates with host immune cells, such as macrophages, T cells, and B cells in the peritoneal cavity. Further, the regulatory T cells increased in the peritoneal cavity. These results indicated that, in addition to helping the innate immunity, hAFSCs could also aid the acquired immune system in vivo against inflammation-related diseases by increasing regulatory T cells.

Transient ventricular bigeminy during emergence from general anesthesia in a pediatric patient with catecholaminergic polymorphic ventricular tachycardia.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare genetic disease that is characterized by ventricular arrhythmias and sudden death, induced by exogenous and endogenous catecholamine. We performed general anesthesia for dental treatment of multiple teeth in a 7-year-old boy with CPVT. To avoid sympathetic tone, anesthesia was maintained by total intravenous anesthesia, but ventricular bigeminy was induced by stimulation on emergence form general anesthesia. Although bigeminy in the present case might have been less likely to induce a fatal arrhythmia, we should keep in mind that a small amount of sympathetic tone may induce arrhythmias in a patient with CPVT.

Mast cells can produce transforming growth factor ß1 and promote tissue fibrosis during the development of Sjögren's syndrome-related sialadenitis.

OBJECTIVES: This study investigated the associations of mast cells with immune-mediated inflammation and fibrosis in patients with primary Sjögren's syndrome (pSS); it also explored the underlying pathophysiology of pSS-related sialadenitis. METHODS: Twenty-two patients with pSS and 10 patients with sicca (control individuals) underwent labial salivary gland biopsies. Sections were subjected to staining and immunofluorescence analyses. HMC-1 human mast cells were cocultured with fibroblasts in vitro; fibroblasts were also grown in HMC-1 conditioned medium. mRNA levels of collagen Type I (Col1a) and transforming growth factor (TGF)ß1 were analysed in cultured cells. RESULTS: Mast cell numbers in labial salivary glands were significantly greater in patients with pSS than in control individuals. In salivary glands from patients with pSS, mast cell number was significantly correlated with fibrosis extent; moreover, mast cells were located near fibrous tissue and expressed TGFß1. Col1a and TGFß1 mRNAs were upregulated in cocultured fibroblasts and HMC-1 cells, respectively. Fibroblasts cultured in HMC-1 conditioned medium exhibited upregulation of Col1a mRNA; this was abrogated by TGFß1 neutralizing antibodies. CONCLUSIONS: Mast cell numbers were elevated in patients with pSS-related sialadenitis; these cells were located near fibroblasts and expressed TGFß1. TGFß1 could induce collagen synthesis in fibroblasts, which might contribute to fibrosis.

The Efficacy of Transarterial Embolization for Postpartum Hemorrhage Complicated with Disseminated Intravascular Coagulation: A Single-Center Experience.

Indications for the use of transarterial embolization (TAE) for postpartum hemorrhage (PPH) have been established. However, the efficacy of TAE for PPH complicated by disseminated intravascular coagulation (DIC) remains controversial. In this study, we investigated the efficacy of TAE for PPH complicated by DIC. A database review was conducted to identify patients who were treated with TAE for PPH at our hospital. TAE was performed in 41 patients during the study period. Effective hemostasis was achieved in all cases, but additional procedures, such as re-embolization or hysterectomy, were required in five patients (12.2%). The typical causes of PPH included uterine atony (18 cases), placenta previa (15 cases), amniotic fluid embolism (DIC-type) (11 cases), and placenta accreta spectrum (10 cases). The mean blood loss was 3836 mL. The mean obstetrical DIC and the International Society on Thrombosis and Hemostasis DIC scores were 7.9 and 2.6, respectively. The efficacy of hemostasis was comparable between patients with and without DIC. However, the complete success rate of TAE was lower in patients with DIC as the condition worsened than that in non-DIC patients. Overall, TAE is effective as a minimally invasive treatment for PPH complicated by DIC.

Clinical Results of a Massive Blood Transfusion Protocol for Postpartum Hemorrhage in a University Hospital in Japan: A Retrospective Study.

Background and objectives: Massive postpartum hemorrhage (PPH) is the most common cause of maternal death worldwide. A massive transfusion protocol (MTP) may be used to provide significant benefits in the management of PPH; however, only a limited number of hospitals use MTP protocol to manage massive obstetric hemorrhages, especially in Japan. This study aimed to assess the clinical outcomes in patients in whom MTP was activated in our hospital. Materials and Methods: We retrospectively reviewed the etiology of PPH, transfusion outcomes, and laboratory findings among the patients treated with MTP after delivery in our hospital. Results: MTP was applied in 24 cases (0.7% of deliveries). Among them, MTP was activated within 2 h of delivery in 15 patients (62.5%). The median estimated blood loss was 5017 mL. Additional procedures to control bleeding were performed in 19 cases, including transarterial embolization (18 cases, 75%) and hysterectomy (1 case, 4.2%). The mean number of units of red blood cells, fresh frozen plasma, and platelets were 17.9, 20.2, and 20.4 units, respectively. The correlation coefficients of any two items among red blood cells, fresh frozen plasma, platelets, blood loss, and obstetrical disseminated intravascular coagulation score ranged from 0.757 to 0.892, indicating high levels of correlation coefficients. Although prothrombin time and activated partial thromboplastin time levels were significantly higher in the <150 mg/dL fibrinogen group than in the ≥150 mg/dL fibrinogen group at the onset of PPH, the amount of blood loss and blood transfusion were comparable between the two groups. Conclusions: Our MTP provides early access to blood products for patients experiencing severe PPH and could contribute to improving maternal outcomes after resuscitation in our hospital. Our study suggests the implementation of a hospital-specific MTP protocol to improve the supply and utilization of blood products to physicians managing major obstetric hemorrhage.

Amniotic fluid stem cells as a novel strategy for the treatment of fetal and neonatal neurological diseases.

Even in the context of modern medicine, infants with fetal and neonatal neurological diseases such as cerebral palsy and myelomeningocele suffer serious long-lasting impairment due to the irreversible neuronal damage. The promotion of neurologically intact survival in patients with perinatal intractable neurological diseases requires the development of novel strategies. One promising strategy involves the use of human amniotic fluid stem cells (hAFSCs), which have attracted much attention in recent years and are known to exert anti-inflammatory and neuroprotective effects. In recent years, the therapeutic effects of hAFSCs on fetal-neonatal neurological diseases have become evident as per intense research efforts by our group and others. Specifically, hAFSCs administered into the nasal cavity migrated to the brain and controlled local inflammation in a rodent model of neonatal hypoxic-ischemic encephalopathy. In contrast, hAFSCs administered intraperitoneally did not migrate to the brain; they rather formed spheroids in the abdominal cavity, resulting in the suppression of systemic inflammation (including in the brain) via the secretion of anti-inflammatory cytokines in concert with peritoneal macrophages in a rodent model of periventricular leukomalacia. Moreover, studies in a rat model of myelomeningocele suggested that hAFSCs administered in utero secreted hepatocyte growth factor and protected the exposed spinal cord during pregnancy. Importantly, autologous hAFSCs, whose use for fetal-neonatal treatment does not raise ethical issues, can be collected during pregnancy and prepared in sufficient numbers for therapeutic use. This article outlines the results of preclinical research on fetal stem cell therapy, mainly involving hAFSCs, in the context of perinatal neurological diseases.

Comprehensive review of lower third molar management: A guide for improved informed consent.

Lower third molar removal is the most commonly performed dental surgical procedure. Nevertheless, it is difficult to ensure that all the informed consent forms given to patients are based on the best evidence as many newer publications could change the conclusions of previous research. Therefore, the goal of this review article is to cover existing meta-analyses, randomized control trials, and related articles in order to collect data for improved and more current informed consent.

Cell sheets using human amniotic fluid stem cells reduce tissue fibrosis in murine full-thickness skin wounds.

The use of mesenchymal stem cell sheets is a promising strategy for skin regeneration. The injection of dissociated human amniotic fluid stem cells (hAFSCs) was recently found to accelerate cutaneous wound healing with reduced fibrotic scarring, similar to fetal wound healing. However, the use of hAFSCs in applications of cell sheet technology remains limited. The aim of this study was to determine the in vivo efficacy of in vitro-cultured hAFSC sheets in wound healing. The cell sheets were characterized by immunohistochemistry and RT-qPCR and grafted onto full-thickness wounds in BALB/c mice. The wound size was measured, and re-epithelialization, granulation tissue area, and collagen content of the regenerated wound were analyzed histologically. Although the hAFSC sheet contained abundant extracellular matrix molecules and expressed high levels of anti-fibrotic mediators, its grafting did not affect wound closure or the size of the granulation tissue area. In contrast, the organization of type I collagen bundles in the regenerated wound was markedly reduced, while the levels of type III collagen were increased after implantation of the hAFSC sheet. These results suggest that hAFSC sheets can exert anti-fibrotic properties without delaying wound closure.

Prophylactic Therapy with Human Amniotic Fluid Stem Cells Improves Long-Term Cognitive Impairment in Rat Neonatal Sepsis Survivors.

A systemic inflammatory response induces multiple organ dysfunction and results in poor long-term neurological outcomes in neonatal sepsis. However, there is no effective therapy for treating or preventing neonatal sepsis besides antibiotics and supportive care. Therefore, a novel strategy to improve neonatal sepsis-related morbidity and mortality is desirable. Recently, we reported that prophylactic therapy with human amniotic stem cells (hAFSCs) improved survival in a rat model of lipopolysaccharide (LPS)-induced neonatal sepsis through immunomodulation. Besides improving the mortality, increasing survival without major morbidities is an important goal of neonatal intensive care for neonatal sepsis. This study investigated long-term neurological outcomes in neonatal sepsis survivors treated with hAFSCs using the LPS-induced neonatal sepsis model in rats. We found that prophylactic therapy with hAFSCs improved spatial awareness and memory-based behavior in neonatal sepsis survivors at adolescence in rats. The treatment suppressed acute reactive gliosis and subsequently reduced astrogliosis in the hippocampal region over a long period of assessment. To the best of our knowledge, this is the first report that proves the concept that hAFSC treatment improves cognitive impairment in neonatal sepsis survivors. We demonstrate the efficacy of hAFSC therapy in improving the mortality and morbidity associated with neonatal sepsis.

Prophylactic therapy with human amniotic fluid stem cells improved survival in a rat model of lipopolysaccharide-induced neonatal sepsis through immunomodulation via aggregates with peritoneal macrophages.

BACKGROUND: Despite recent advances in neonatal care, sepsis remains a leading cause of mortality in neonates. Mesenchymal stem cells derived from various tissues, such as bone marrow, umbilical cord, and adipose tissue, have beneficial effects on adult sepsis. Although human amniotic fluid stem cells (hAFSCs) have mesenchymal stem cell properties, the efficacy of hAFSCs on neonatal sepsis is yet to be elucidated. This study aimed to investigate the therapeutic potential of hAFSCs on neonatal sepsis using a rat model of lipopolysaccharide (LPS)-induced sepsis. METHODS: hAFSCs were isolated as CD117-positive cells from human amniotic fluid. Three-day-old rat pups were intraperitoneally treated with LPS to mimic neonatal sepsis. hAFSCs were administered either 3 h before or at 0, 3, or 24 h after LPS exposure. Serum inflammatory cytokine levels, gene expression profiles from spleens, and multiple organ damage were analyzed. hAFSC localization was determined in vivo. In vitro LPS stimulation tests were performed using neonatal rat peritoneal macrophages co-cultured with hAFSCs in a cell-cell contact-dependent/independent manner. Immunoregulation in the spleen was determined using a DNA microarray analysis. RESULTS: Prophylactic therapy with hAFSCs improved survival in the LPS-treated rats while the hAFSCs transplantation after LPS exposure did not elicit a therapeutic response. Therefore, hAFSC pretreatment was used for all subsequent studies. Inflammatory cytokine levels were elevated after LPS injection, which was attenuated by hAFSC pretreatment. Subsequently, inflammation-induced damages in the brain, lungs, and liver were ameliorated. hAFSCs aggregated with peritoneal macrophages and/or transiently accumulated in the liver, mesentery, and peritoneum. Paracrine factors released by hAFSCs induced M1-M2 macrophage polarization in a cell-cell contact-independent manner. Direct contact between hAFSCs and peritoneal macrophages further enhanced the polarization. Microarray analysis of the spleen showed that hAFSC pretreatment reduced the expression of genes involved in apoptosis and inflammation and subsequently suppressed toll-like receptor 4 signaling pathways. CONCLUSIONS: Prophylactic therapy with hAFSCs improved survival in a rat model of LPS-induced neonatal sepsis. These effects might be mediated by a phenotypic switch from M1 to M2 in peritoneal macrophages, triggered by hAFSCs in a cell-cell contact-dependent/independent manner and the subsequent immunomodulation of the spleen.

In Utero Amniotic Fluid Stem Cell Therapy Protects Against Myelomeningocele via Spinal Cord Coverage and Hepatocyte Growth Factor Secretion.

Despite the poor prognosis associated with myelomeningocele (MMC), the options for prenatal treatments are still limited. Recently, fetal cellular therapy has become a new option for treating birth defects, although the therapeutic effects and mechanisms associated with such treatments remain unclear. The use of human amniotic fluid stem cells (hAFSCs) is ideal with respect to immunoreactivity and cell propagation. The prenatal diagnosis of MMC during early stages of pregnancy could allow for the ex vivo proliferation and modulation of autologous hAFSCs for use in utero stem cell therapy. Therefore, we investigated the therapeutic effects and mechanisms of hAFSCs-based treatment for fetal MMC. hAFSCs were isolated as CD117-positive cells from the amniotic fluid of 15- to 17-week pregnant women who underwent amniocentesis for prenatal diagnosis and consented to this study. Rat dams were exposed to retinoic acid to induce fetal MMC and were subsequently injected with hAFSCs in each amniotic cavity. We measured the exposed area of the spinal cord and hepatocyte growth factor (HGF) levels at the lesion. The exposed spinal area of the hAFSC-treated group was significantly smaller than that of the control group. Immunohistochemical analysis demonstrated a reduction in neuronal damage such as neurodegeneration and astrogliosis in the hAFSC-treated group. Additionally, in lesions of the hAFSC-treated group, HGF expression was upregulated and HGF-positive hAFSCs were identified, suggesting that these cells migrated to the lesion and secreted HGF to suppress neuronal damage and induce neurogenesis. Therefore, in utero hAFSC therapy could become a novel strategy for fetal MMC. Stem Cells Translational Medicine 2019;8:1170-1179.

Expression and role of regulator of G-protein signaling 5 in squamous cell carcinoma of the tongue.

Regulator of G-protein signaling (RGS) 5 acts as a GTPase-activating protein to negatively regulate G-protein signaling. RGS5 is reportedly related to the invasion and metastasis of cancers, such as nonsmall lung cancer and hepatocellular carcinoma. We examined RGS5 expression and its relationship with invasion in squamous cell carcinoma (SCC) of the tongue. For immunohistochemical analysis of RGS5, we used SCC tissues of the tongue obtained from 43 patients. We examined the relationship between RGS5 expression in the deepest point of invasion and clinicopathological features. Because the invasion and metastasis of cancers are related to epithelial-mesenchymal transition (EMT), we carried out staining for N-cadherin, vimentin, and E-cadherin to examine the relationship between EMT and RGS5. RGS5 expression in the deepest point of invasion in SCC of the tongue was observed in 32 cases (75%). Immunohistochemical analysis revealed a significant correlation between RGS5 expression in the aggressive invasion pattern, invasion depth, and lymphovascular invasion. Kaplan-Meier analysis revealed that high RGS5 expression was associated with postoperative early lymph node metastasis. Further, a significant positive correlation was observed between RGS5 and N-cadherin (P = 0.0003) and vimentin (P < 0.0001). In contrast, E-cadherin and RGS5 or vimentin were significantly negatively correlated (P < 0.0001-0.005). The findings indicate that RGS5 expression is related to tumor invasion and EMT in SCC of the tongue and that RGS5 may predict postoperative early lymph node metastasis. Therefore, RGS5 may be a useful prognostic biomarker of the surgically resected SCC and a potential target of molecular therapy for treating SCC of the tongue.

The neurorestorative effect of human amniotic fluid stem cells on the chronic phase of neonatal hypoxic-ischemic encephalopathy in mice.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) remains a major cause of cerebral palsy. Increasing evidence has suggested that mesenchymal stem cells have a favorable effect on HIE. However, the efficacy of human amniotic fluid stem cells (hAFS) for HIE, especially in the chronic phase, remains unclear. The aim of this study was to determine the neurorestorative effect of hAFS on the chronic phase of HIE. METHODS: hAFS were isolated from AF cells as CD117-positive cells. HI was induced in 9-day-old mice. Animals intranasally received hAFS or phosphate-buffered saline at 10 days post HI and were harvested for histological analysis after functional tests at 21 days post HI. We also implanted PKH26-positive hAFS to assess their migration to the brain. Finally, we determined gene expressions of trophic factors in hAFS co-cultured with HI brain extract. RESULTS: hAFS improved sensorimotor deficits in HIE by gray and white matter restoration and neuroinflammation reduction followed by migration to the lesion. Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), hepatocyte growth factor (HGF), and stromal cell-derived factor-1 (SDF-1) gene expressions in hAFS were elevated when exposed to HI-induced brain extract. CONCLUSION: hAFS induced functional recovery by exerting neurorestorative effects in HIE mice, suggesting that intranasal administration of hAFS could be a novel treatment for HIE, especially in the chronic phase.