The FAT1 gene functions as a tumor suppressor or promoter and remains incompletely understood. We examined the clinical significance of FAT1 in head and neck squamous cell carcinoma (HNSCC) using ...four publicly available HNSCC cohorts and one HNSCC cohort enrolled at a tertiary medical center. We developed FAT1 signatures reflecting FAT1 mutations and mRNA expression using one cohort. Patients with HNSCC were classified into FAT1‐associated low risk (FAT1‐LR; n = 195) and FAT1‐associated high risk (FAT1‐HR; n = 371) subgroups. The five‐year overall survival and recurrence‐free survival rates were significantly lower in the FAT1‐HR subgroup than in the FAT1‐LR subgroup (P = 0.01 and 0.003, respectively). The clinical significance of FAT1 was validated using four independent cohorts. Cox proportional hazards models showed that the FAT1 signature was an independent prognostic factor for HNSCC patients. In addition, FAT1 signature was associated with the response to radiotherapy, advanced stage, and human papilloma virus (HPV) status in HNSCC patients. In conclusion, the FAT1 gene signature was associated with prognosis of HNSCC and may help to provide personalized treatments for HNSCC patients.
In our study, we classified patients with head and neck squamous cell carcinoma (HNSCC) as FAT1‐associated low risk and FAT1‐associated high risk, based on our predefined FAT1 gene‐related molecular signature. The prognosis of patients with HNSCC was significantly different between both subgroups. In conclusion, the FAT1 signature served as an independent prognostic factor for HNSCC and was associated with response to radiation therapy.
Orthohantaviruses, etiological agents of hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome, pose a critical public health threat worldwide. Hantaan orthohantavirus ...(HTNV) outbreaks are particularly endemic in Gyeonggi Province in northern area of the Republic of Korea (ROK). Small mammals were collected from three regions in the Gyeonggi Province during 2017 and 2018. Serological and molecular prevalence of HTNV was 25/201 (12.4%) and 10/25 (40%), respectively. A novel nanopore‐based diagnostic assay using a cost‐efficient Flongle chip was developed to rapidly and sensitively detect HTNV infection in rodent specimens within 3 h. A rapid phylogeographical surveillance of HTNV at high‐resolution phylogeny was established using the amplicon‐based Flongle sequencing. In total, seven whole‐genome sequences of HTNV were newly obtained from wild rodents collected in Paju‐si (Gaekhyeon‐ri) and Yeoncheon‐gun (Hyeonga‐ri and Wangnim‐ri), Gyeonggi Province. Phylogenetic analyses revealed well‐supported evolutionary divergence and genetic diversity, enhancing the resolution of the phylogeographic map of orthohantaviruses in the ROK. Incongruences in phylogenetic patterns were identified among HTNV tripartite genomes, suggesting differential evolution for each segment. These findings provide crucial insights into on‐site diagnostics, genome‐based surveillance, and the evolutionary dynamics of orthohantaviruses to mitigate hantaviral outbreaks in HFRS‐endemic areas in the ROK.
Targeting autophagy is a promising therapeutic approach in cancer therapy. Here, we screened 30 traditional herbal medicines to identify novel autophagy regulators and found that Platycodon ...grandiflorus (PG) and platycodin D (PD), a triterpenoid saponin from PG, inhibited autophagy in glioblastoma multiforme (GBM) cells. Mechanistically, PD prevented lysosomal degradation and the fusion between autophagosomes and lysosomes by inducing sequestration of free cholesterol in lysosomes. The autophagy inhibitory effect of PD was mimicked by both genetic and pharmacological inhibition of Niemann‐Pick C1 (NPC1), which exports low‐density lipoprotein (LDL)‐derived cholesterol from lysosomes. Moreover, PD promoted the uptake of exogenous LDL cholesterol via upregulation of LDL receptor (LDLR), leading to further accumulation of cholesterol within lysosomes and GBM cell death. Importantly, these phenomena were more pronounced in LDLR‐overexpressing GBM cells than in normal astrocytes. Finally, blockade of cholesterol uptake by LDLR knockdown reversed the PD‐induced inhibition of autophagy and GBM cell growth. Our study proposes that PD could be a potent anti‐GBM drug by disrupting cholesterol trafficking and autophagy.
Our study demonstrates that platycodin D (PD) increased cholesterol content in lysosomes and prevented lysosomal fusion with autophagosomes in glioblastoma multiforme (GBM) cells. Low cholesterol availability increased LDLR expression and uptake of LDL cholesterol, leading to accumulation of cholesterol in lysosomes and cell death. The anticancer effect of PD correlated with LDLR overexpression in GBM cells, which is in contrast to normal astrocytes expressing low levels of LDLR.
Background
Spousal donors have gradually been accepted as an alternative living liver donors to alleviate the organ shortage and prevent donations from children. No information is available regarding ...the effects of spousal donation on donor safety and recipient outcomes. Our purpose in this study was to determine how spousal liver grafts in living donor liver transplantation (LDLT) affect donor safety and recipient outcomes compared with those of LDLT from children.
Methods
We retrospectively analyzed 656 patients, including spouses and children, who underwent a right or extended right hepatectomy for living liver donation between January 2009 and December 2018.
Results
Spouses represented 18.8% (
n
= 123) of living liver donors. Female donors comprised 78.9% (
n
= 97) of spousal donors, and the proportion of male donors in the children group was 72.6% (
n
= 387). The mean donor operation time of the spousal group was shorter than that of the children group (330 min vs. 358 min;
P
= 0.011), and the complication rate in the spousal group was lower than that in the children group (12.2% vs. 22.9%;
P
= 0.006). However, there were no differences in severe complication rates, hospitalization, or liver function tests between the 2 groups at 3 months after donor surgery. The overall survival of recipients in the spousal group was not reduced compared to that of recipients in the children group.
Conclusion
The present study suggests that, with careful selection, spousal donation is feasible and safe in LDLT.
Tissue regeneration includes delivering specific types of cells or cell products to injured tissues or organs for restoration of tissue and organ function. Stem cell therapy has drawn considerable ...attention since transplantation of stem cells can overcome the limitations of autologous transplantation of patient's tissues; however, it is not perfect for treating diseases. To overcome the hurdles associated with stem cell therapy, tissue engineering techniques have been developed. Development of stem cell technology in combination with tissue engineering has opened new ways of producing engineered tissue substitutes. Several studies have shown that this combination of tissue engineering and stem cell technologies enhances cell viability, differentiation, and therapeutic efficacy of transplanted stem cells.
Stem cells that can be used for tissue regeneration include mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells. Transplantation of stem cells alone into injured tissues exhibited low therapeutic efficacy due to poor viability and diminished regenerative activity of transplanted cells. In this review, we will discuss the progress of biomedical engineering, including scaffolds, biomaterials, and tissue engineering techniques to overcome the low therapeutic efficacy of stem cells and to treat human diseases.
The combination of stem cell and tissue engineering techniques overcomes the limitations of stem cells in therapy of human diseases, and presents a new path toward regeneration of injured tissues.
This study aimed to evaluate the characteristics of reflux in proton pump inhibitor (PPI) nonresponders vs responders in patients with laryngopharyngeal reflux (LPR) by using 24-hour multichannel ...intraluminal impedance-pH (MII-pH) monitoring.
Prospective cohort study.
A tertiary care otolaryngology clinic.
Patients with typical LPR symptoms showing >1 proximal reflux episode were considered to have LPR and investigated prospectively. Patients were prescribed high-dose PPI twice daily and followed up for at least 2 months. Patients with LPR showing a ≥50% decrease in the follow-up reflux symptom index score during treatment periods as compared with pretreatment were defined as responders; others were defined as nonresponders. Various parameters in 24-hour MII-pH monitoring between nonresponders and responders with LPR were compared with Student's
test and receiver operating characteristic curve.
Eighty patients were diagnosed with LPR and categorized as nonresponders (n = 19) and responders (n = 61). Proximal all reflux time and proximal longest reflux time in various MII parameters were higher in responders than in nonresponders (
= .0040 and .0216, respectively). Proximal all reflux time >0.000517% was a better cutoff value to predict responders with LPR as compared with the proximal longest reflux time >0.61 minutes (sensitivity + specificity: 1.317 vs 1.291).
Proximal all reflux time in various 24-hour MII-pH monitoring parameters can be helpful to predict the response to PPI therapy in patients with LPR. These findings will help establish a personalized therapeutic scheme for patients with LPR.
Hepatitis E virus (HEV), an emerging zoonotic pathogen, poses a significant public health concern worldwide. Recently, rat HEV (Rocahepevirus ratti genotype C1; HEV‐C1) has been reported to cause ...zoonotic infections and hepatitis in humans. Human infections with HEV‐C1 are considered to be underestimated worldwide due to limited knowledge of transmission routes, genome epidemiology, and the risk assessment of zoonosis associated with these viruses. A total of 186 wild Norway rats (Rattus norvegicus) were collected from the Republic of Korea (ROK) between 2011 and 2021. The prevalence of HEV‐C1 RNA was 8 of 180 (4.4%) by reverse‐transcription polymerase chain reaction. We first reported three nearly whole‐genome sequences of HEV‐C1 newly acquired from urban rats in the ROK. Phylogenetic analysis demonstrated that Korea‐indigenous HEV‐C1 formed an independent genetic group with those derived from R. norvegicus rats in other countries, indicating geographical and genetic diversity. Our findings provide critical insights into the molecular prevalence, genome epidemiology, and zoonotic potential of Rocahepevirus. This report raises awareness of the presence of Rocahepevirus‐related hepatitis E among physicians in the ROK.
Though Sanggenon G (SanG) from root bark of Morus alba was known to exhibit anti‐oxidant and anti‐depressant effects, its underlying mechanisms still remain unclear. Herein SanG reduced the viability ...of A549 and H1299 non‐small lung cancer cells (NSCLCs). Also, SanG increased sub‐G1 population via inhibition of cyclin D1, cyclin E, CDK2, CDK4 and Bcl‐2, cleavages of poly (ADP‐ribose) polymerase (PARP) and caspase‐3 in A549 and H1299 cells. Of note, SanG effectively inhibited c‐Myc expression by activating ribosomal protein L5 (RPL5) and reducing c‐Myc stability even in the presence of cycloheximide and 20% serum in A549 cells. Furthermore, SanG enhanced the apoptotic effect with doxorubicin in A549 cells. Taken together, our results for the first time provide novel evidence that SanG suppresses proliferation and induces apoptosis via caspase‐3 activation and RPL5 mediated inhibition of c‐Myc with combinational potential with doxorubicin.
Oxaliplatin, a well-known chemotherapeutic agent, can induce severe neuropathic pain, which can seriously decrease the quality of life of patients. JI017 is an herb mixture composed of
,
, and
. Its ...anti-tumor effect has been reported; however, the efficacy of JI017 against oxaliplatin-induced allodynia has never been explored. Single oxaliplatin injection 6 mg/kg, intraperitoneal, (i.p.) induced both cold and mechanical allodynia, and oral administration of JI017 (500 mg/kg) alleviated cold but not mechanical allodynia in mice. Real-time polymerase chain reaction (PCR) analysis demonstrated that the upregulation of mRNA of spinal transient receptor potential vanilloid 1 (TRPV1) and astrocytes following oxaliplatin injection was downregulated after JI017 treatment. Moreover, TRPV1 expression and the activation of astrocytes were intensely increased in the superficial area of the spinal dorsal horn after oxaliplatin treatment, whereas JI017 suppressed both. The administration of TRPV1 antagonist capsazepine, intrathecal (i.t.), 10 μg attenuated the activation of astrocytes in the dorsal horn, demonstrating that the functions of spinal TRPV1 and astrocytes are closely related in oxaliplatin-induced neuropathic pain. Altogether, these results suggest that JI017 may be a potent candidate for the management of oxaliplatin-induced neuropathy as it decreases pain, spinal TRPV1, and astrocyte activation.
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