Porcine Follicular Fluid-Derived Exosome: The Pivotal Material for Porcine Oocyte Maturation in Lipid Antioxidant Activity.

Several studies have examined exosomes derived from porcine follicular fluid (FF), but few have reported their application in controlled experiments. The main concern in the field of embryology may be that controlled conditions, such as using a defined medium intermittently, cause poor results in mammalian oocyte maturation and embryo development. The first reason is the absence of the FF, which copes with the majority of the processes emerging in oocytes and embryos. Therefore, we added exosomes derived from porcine FF to the maturation medium of porcine oocytes. For morphological assessment, cumulus cell expansion and subsequent embryonic development were evaluated. Moreover, several stainings, such as glutathione (GSH) and reactive oxygen species (ROS), fatty acid, ATP, and mitochondrial activity, as well as evaluations of gene expression and protein analysis, were used for the functional verification of exosomes. When the oocytes were treated with exosomes, the lipid metabolism and cell survival of the oocytes were fully recovered, as well as morphological evaluations compared to the porcine FF-excluded defined medium. Therefore, controlled experiments may produce reliable data if the exosomes are treated with the desired amounts, and we suggest applying FF-derived exosomes to promote experimental data when performing controlled experiments in embryology.

Comparative Analysis of Water Extracts from Roselle (Hibiscus sabdariffa L.) Plants and Callus Cells: Constituents, Effects on Human Skin Cells, and Transcriptome Profiles.

Roselle (Hibiscus sabdariffa L.) is a plant that has traditionally been used in various food and beverage products. Here, we investigated the potential of water extracts derived from Roselle leaves and callus cells for cosmetic and pharmaceutical purposes. We generated calluses from Roselle leaves and produced two different water extracts through heat extraction, which we named Hibiscus sabdariffa plant extract (HSPE) and Hibiscus sabdariffa callus extract (HSCE). HPLC analysis showed that the two extracts have different components, with nucleic acids and metabolites such as phenylalanine and tryptophan being the most common components in both extracts. In vitro assays demonstrated that HSCE has strong anti-melanogenic effects and functions for skin barrier and antioxidant activity. Transcriptome profiling of human skin cells treated with HSPE and HSCE showed significant differences, with HSPE having more effects on human skin cells. Up-regulated genes by HSPE function in angiogenesis, the oxidation-reduction process, and glycolysis, while up-regulated genes by HSCE encode ribosome proteins and IFI6, functioning in the healing of radiation-injured skin cells. Therefore, we suggest that the two extracts from Roselle should be applied differently for cosmetics and pharmaceutical purposes. Our findings demonstrate the potential of Roselle extracts as a natural source for skincare products.

Comprehensive Molecular Characterization of Adenocarcinoma of the Gastroesophageal Junction Between Esophageal and Gastric Adenocarcinomas.

OBJECTIVE: To investigate the molecular characteristics of AGEJ compared with EAC and gastric adenocarcinoma. SUMMARY OF BACKGROUND DATA: Classification of AGEJ based on differential molecular characteristics between EAC and gastric adenocarcinoma has been long-standing controversy but rarely conducted due to anatomical ambiguity and epidemiologic difference. METHODS: The molecular classification model with Bayesian compound covariate predictor was developed based on differential mRNA expression of EAC (N = 78) and GCFB (N = 102) from the Cancer Genome Atlas (TCGA) cohort. AGEJ/cardia (N = 48) in TCGA cohort and AGEJ/upper third GC (N = 46 pairs) in Seoul National University cohort were classified into the EAC-like or GCFB-like groups whose genomic, transcriptomic, and proteomic characteristics were compared. RESULTS: AGEJ in both cohorts was similarly classified as EAC-like (31.2%) or GCFB-like (68.8%) based on the 400-gene classifier. The GCFB-like group showed significantly activated phosphoinositide 3-kinase-AKT signaling with decreased expression of ERBB2. The EAC-like group presented significantly different alternative splicing including the skipped exon of RPS24, a significantly higher copy number amplification including ERBB2 amplification, and increased protein expression of ERBB2 and EGFR compared with GCFB-like group. High-throughput 3D drug test using independent cell lines revealed that the EAC-like group showed a significantly better response to lapatinib than the GCFB-like group (P = 0.015). CONCLUSIONS: AGEJ was the combined entity of the EAC-like and GCFB-like groups with consistently different molecular characteristics in both Seoul National University and TCGA cohorts. The EAC-like group with a high Bayesian compound covariate predictor score could be effectively targeted by dual inhibition of ERBB2 and EGFR.

Co-expression of cancer driver genes: IDH-wildtype glioblastoma-derived tumorspheres.

BACKGROUND: Driver genes of GBM may be crucial for the onset of isocitrate dehydrogenase (IDH)-wildtype (WT) glioblastoma (GBM). However, it is still unknown whether the genes are expressed in the identical cluster of cells. Here, we have examined the gene expression patterns of GBM tissues and patient-derived tumorspheres (TSs) and aimed to find a progression-related gene. METHODS: We retrospectively collected primary IDH-WT GBM tissue samples (n = 58) and tumor-free cortical tissue samples (control, n = 20). TSs are isolated from the IDH-WT GBM tissue with B27 neurobasal medium. Associations among the driver genes were explored in the bulk tissue, bulk cell, and a single cell RNAsequencing techniques (scRNAseq) considering the alteration status of TP53, PTEN, EGFR, and TERT promoter as well as MGMT promoter methylation. Transcriptomic perturbation by temozolomide (TMZ) was examined in the two TSs. RESULTS: We comprehensively compared the gene expression of the known driver genes as well as MGMT, PTPRZ1, or IDH1. Bulk RNAseq databases of the primary GBM tissue revealed a significant association between TERT and TP53 (p < 0.001, R = 0.28) and its association increased in the recurrent tumor (p < 0.001, R = 0.86). TSs reflected the tissue-level patterns of association between the two genes (p < 0.01, R = 0.59, n = 20). A scRNAseq data of a TS revealed the TERT and TP53 expressing cells are in a same single cell cluster. The driver-enriched cluster dominantly expressed the glioma-associated long noncoding RNAs. Most of the driver-associated genes were downregulated after TMZ except IGFBP5. CONCLUSIONS: GBM tissue level expression patterns of EGFR, TERT, PTEN, IDH1, PTPRZ1, and MGMT are observed in the GBM TSs. The driver gene-associated cluster of the GBM single cells were enriched with the glioma-associated long noncoding RNAs.

Failure of a patient-derived xenograft for brain tumor model prepared by implantation of tissue fragments.

BACKGROUND: With the continuing development of new anti-cancer drugs comes a need for preclinical experimental models capable of predicting the clinical activity of these novel agents in cancer patients. However existing models have a limited ability to recapitulate the clinical characteristics and associated drug sensitivity of tumors. Among the more promising approaches for improving preclinical models is direct implantation of patient-derived tumor tissue into immunocompromised mice, such as athymic nude or non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. In the current study, we attempted to develop patient-derived xenograft (PDX) models using tissue fragments from surgical samples of brain tumors. METHODS: In this approach, tiny tissue fragments of tumors were biopsied from eight brain tumor patients-seven glioblastoma patients and one primitive neuroectodermal tumor patient. Two administration methods-a cut-down syringe and a pipette-were used to implant tissue fragments from each patient into the brains of athymic nude mice. RESULTS: In contrast to previous reports, and contrary to our expectations, we found that none of these fragments from brain tumor biopsies resulted in the successful establishment of xenograft tumors. CONCLUSIONS: These results suggest that fragments of surgical specimens from brain tumor patients are unsuitable for implementation of brain tumor PDX models, and instead recommend other in vivo testing platforms for brain tumors, such as cell-based brain tumor models.

Success of tumorsphere isolation from WHO grade IV gliomas does not correlate with the weight of fresh tumor specimens: an immunohistochemical characterization of tumorsphere differentiation.

BACKGROUND: A trend of stage-by-stage increase in tumorsphere (TS) formation from glioma samples has been reported. Despite this trend, not all surgical specimens give rise to TSs, even World Health Organization (WHO) grade IV gliomas. Furthermore, it has been reported that differences in overall survival of primary glioblastoma patients depends on the propensity of their tumors to form TSs. However, the weights of fresh specimens vary from one surgical isolate to the next. METHODS: Accordingly, we evaluated the relationship between the weights of surgical specimens in WHO grade IV gliomas with the capacity to isolate TSs. Thirty-five fresh WHO grade IV glioma specimens were separated into two groups, based on whether they were positive or negative for TS isolation, and the relationship between TS isolation and weight of surgical specimens was assessed. RESULTS: We observed no significant difference in the weights of surgical samples in the two groups, and found that the optimal weight of specimens for TSs isolation was 500 mg. CONCLUSION: Thus, contrary to our expectations, the ability to isolate TSs from WHO grade IV glioma specimens was not related to the weight of fresh specimens.

Cannabis sativa (Hemp) seed-derived peptides WVYY and PSLPA modulate the Nrf2 signaling pathway in human keratinocytes.

Cannabis sativa (Hemp) seeds are used widely for cosmetic and therapeutic applications, and contain peptides with substantial therapeutic potential. Two key peptides, WVYY and PSLPA, extracted from hemp seed proteins were the focal points of this study. These peptides have emerged as pivotal contributors to the various biological effects of hemp seed extracts. Consistently, in the present study, the biological effects of WVYY and PSLPA were explored. We confirmed that both WVYY and PSLPA exert antioxidant and antibacterial effects and promote wound healing. We hypothesized the involvement of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in these observed effects, given that Nrf2 is reported to be a central player in the regulation of these observed effects. Molecular-level investigations unequivocally confirmed the role of the Nrf2 signaling pathway in the observed effects of WVYY and PSLPA, specifically their antioxidant effects. Our study highlights the therapeutic potential of hemp seed-derived peptides WVYY and PSLPA, particularly with respect to their antioxidant effects, and provides a nuanced understanding of their effects. Further, our findings can facilitate the investigation of targeted therapeutic applications and also underscore the broader significance of hemp extracts in biological contexts.

Transcriptional Changes in Damask Rose Suspension Cell Culture Revealed by RNA Sequencing.

Damask roses (Rosa x damascena) are widely used in cosmetics and pharmaceutics. Here, we established an in vitro suspension cell culture for calli derived from damask rose petals. We analyzed rose suspension cell transcriptomes obtained at two different time points by RNA sequencing to reveal transcriptional changes during rose suspension cell culture. Of the 580 coding RNAs (1.3%) highly expressed in the suspension rose cells, 68 encoded cell wall-associated proteins. However, most RNAs encoded by the chloroplasts and mitochondria are not expressed. Many highly expressed coding RNAs are involved in translation, catalyzing peptide synthesis in ribosomes. Moreover, the amide metabolic process producing naturally occurring alkaloids was the most abundant metabolic process during the propagation of rose suspension cells. During rose cell propagation, coding RNAs involved in the stress response were upregulated at an early stage, while coding RNAs associated with detoxification and transmembrane transport were upregulated at the late stage. We used transcriptome analyses to reveal important biological processes and molecular mechanisms during rose suspension cell culture. Most non-coding (nc) RNAs were not expressed in the rose suspension cells, but a few ncRNAs with unknown functions were highly expressed. The expression of ncRNAs and their target coding RNAs was highly correlated. Taken together, we revealed significant biological processes and molecular mechanisms occurring during rose suspension cell culture using transcriptome analyses.

A Prospective, Multicenter, Observational Study of Surgical vs Nonsurgical Management for Pituitary Apoplexy.

CONTEXT: Pituitary apoplexy (PA) has been traditionally considered a neurosurgical emergency, yet retrospective single-institution studies suggest similar outcomes among patients managed medically. OBJECTIVE: We established a multicenter, international prospective registry to compare presentation and outcomes in PA patients treated with surgery or medical management alone. METHODS: A centralized database captured demographics, comorbidities, clinical presentation, visual findings, hormonal status, and imaging features at admission. Treatment was determined independently by each site. Key outcomes included visual, oculomotor, and hormonal recovery, complications, and hospital length of stay. Outcomes were also compared based on time from symptom onset to surgery, and from admission or transfer to the treating center. Statistical testing compared treatment groups based on 2-sided hypotheses and P less than .05. RESULTS: A total of 100 consecutive PA patients from 12 hospitals were enrolled, and 97 (67 surgical and 30 medical) were evaluable. Demographics, clinical features, presenting symptoms, hormonal deficits, and imaging findings were similar between groups. Severe temporal visual field deficit was more common in surgical patients. At 3 and 6 months, hormonal, visual, and oculomotor outcomes were similar. Stratifying based on severity of visual fields demonstrated no difference in any outcome at 3 months. Timing of surgery did not affect outcomes. CONCLUSION: We found that medical and surgical management of PA yield similar 3-month outcomes. Although patients undergoing surgery had more severe visual field deficits, we could not clearly demonstrate that surgery led to better outcomes. Even without surgery, apoplectic tumor volumes regress substantially within 2 to 3 months, indicating that surgery is not always needed to reduce mass effect.

Changes in the biological characteristics of glioma cancer stem cells after serial in vivo subtransplantation.

PURPOSE: Currently, the interaction between the niche and glioma cancer stem cells (gCSCs) is gaining attention. However, there are few studies concerned with the effects of repeated exposure to a new microenvironment on gCSCs characteristics. In this study, serial in vivo subtransplantation was performed to create a new microenvironment. We evaluated and compared the biological characteristics of gCSCs after serial in vivo subtransplantation. METHODS: We cultured gCSCs from human glioma specimens according to cultured gliomasphere methods. The isolated gCSCs were termed zero-generation gCSCs (G0-gCSCs). By subsequent serial subtransplantation, we obtained first-generation gCSCs (G1-gCSCs) and second-generation gCSCs (G2-gCSCs). We evaluated and compared the biological characteristics of G0-gCSCs, G1-gCSCs, and G2-gCSCs. The in vitro characteristics included the morphology, surface marker profiles, and neural differentiation capacity and the in vivo characteristics was the survival of mice xenografts. Additionally, brain sections were analyzed using PCNA, TUNEL, and CD31 staining. RESULTS: We observed no significant differences in the in vitro characteristics of G0-gCSCs, G1-gCSCs, and G2-gCSCs. However, the survival time of mice glioma xenografts was significantly decreased upon serial subtransplantation. In addition, immunohistochemical analyses showed that the number of TUNEL(+) cells was significantly decreased while the number of CD31(+) cells was significantly increased with serial in vivo subtransplantation. CONCLUSIONS: There were significant in vivo biological changes in gCSCs upon serial in vivo subtransplantation, which were shorter xenograft survival, increased angiogenesis, and decreased apoptosis. This study suggests that the repeated exposure to new microenvironments may affect the biological changes in gCSCs in vivo.

Isolation of tumor spheres and mesenchymal stem-like cells from a single primitive neuroectodermal tumor specimen.

PURPOSE: It has been reported that cancer stem cells (CSCs) can be isolated from primitive neuroectodermal tumor (PNET) specimens. Moreover, mesenchymal stem-like cells (MSLCs) have been isolated from Korean glioma specimens. Here, we tested whether tumor spheres and MSLCs can be simultaneously isolated from a single PNET specimen, a question that has not been addressed. METHODS: We isolated single-cell suspensions from PNET specimens, then cultured these cells using methods for MSLCs or CSCs. Cultured cells were analyzed for surface markers of CSCs using immunocytochemistry and for surface markers of bone marrow-derived mesenchymal stem cells (BM-MSCs) using fluorescence-activated cell sorting (FACS). Tumor spheres were exposed to neural differentiation conditions, and MSLCs were exposed to mesenchymal differentiation conditions. Possible locations of MSLCs within PNET specimens were determined by immunofluorescence analysis of tumor sections. RESULTS: Cells similar to tumor spheres and MSLCs were independently isolated from one of two PNET specimens. Spheroid cells, termed PNET spheres, were positive for CD133 and nestin, and negative for musashi and podoplanin. PNET spheres were capable of differentiation into immature neural cells and astrocytes, but not oligodendrocytes or mature neural cells. FACS analysis revealed that adherent cells isolated from the same PNET specimen, termed PNET-MSLCs, had surface markers similar to BM-MSCs. These cells were capable of mesenchymal differentiation. Immunofluorescence labeling indicated that some CD105(+) cells might be closely related to endothelial cells and pericytes. CONCLUSION: We showed that both tumor spheres and MSLCs can be isolated from the same PNET specimen. PNET-MSLCs occupied a niche in the vicinity of the vasculature and could be a source of stroma for PNETs.

Existence of glioma stroma mesenchymal stemlike cells in Korean glioma specimens.

PURPOSE: It was presented that mesenchymal stem cells (MSCs) can be isolated from western glioma specimens. However, whether MSCs exist in glioma specimens of different ethnicities is unknown. To verify the existence of MSCs in an independent cohort, we undertook studies to isolate MSCs from a group of Korean patients. We hypothesized that cells resembling MSCs that were deemed mesenchymal stemlike cells (MSLCs) exist in an independent cohort of Korean gliomas. METHODS: We cultured fresh glioma specimens using the protocols used for culturing MSCs. The cultured cells were analyzed with fluorescence-activated cell sorting (FACS) for surface markers associated with MSCs. Cultured cells were exposed to mesenchymal differentiation conditions. To presume possible locations of MSLCs in the glioma, sections of glioma were analyzed by immunofluorescent labeling for CD105, CD31, and NG2. RESULTS: From nine of 31 glioma specimens, we isolated cells resembling MSCs, which were deemed Korean glioma stroma MSLCs (KGS-MSLCs). KGS-MSLCs were spindle shaped and adherent to plastic. KGS-MSLCs had similar surface markers to MSCs (CD105(+), CD90(+), CD73(+), and CD45(-)). KGS-MSLCs were capable of mesenchymal differentiation and might be located around endothelial cells, pericytes, and in a disorganized perivascular area inside glioma stroma. CONCLUSIONS: We found that cells resembling MSCs indeed exist in an independent cohort of glioma patients, as presented in western populations. We could presume that the possible location of KGS-MSLCs was in perivascular area or in glioma stroma that was a disorganized vascular niche. It might be possible that KGS-MSLCs could be one of constituent of stroma of glioma microenvironment.

Isolation of glioma cancer stem cells in relation to histological grades in glioma specimens.

PURPOSE: The existence of cancer stem cells (CSCs) in glioblastoma has been proposed. However, the unknown knowledge that is yet to be revealed is the presence of glioma CSCs (gCSCs) in correlation to each WHO grades of glioma. We approached this study with a hypothesis that specimens from high-grade gliomas would have higher isolation rate of gCSCs in comparison to those of lower-grade gliomas. METHODS: The glioma specimens were obtained from patients and underwent gliomasphere assay. The gliomaspheres were chosen to be analyzed with immunocytochemisty for surface markers. Then the selected gliomaspheres were exposed to neural differentiation conditions. Lastly, we made mouse orthotopic glioma models to examine the capacity of gliomagenesis. RESULTS: The gliomaspheres were formed in WHO grade IV (13 of 21) and III (two of nine) gliomas. Among them, WHO grade IV (11 of 13) and III (two of two) gliomaspheres showed similar surface markers to gCSCs and were capable of neural differentiation. Lastly, among the chosen cells, 10 of 11 WHO grade IV and two of two WHO grade III gliomaspheres were capable of gliomagenesis. Thus, overall, the rates of existence of gCSCs were more prominent in high-grade gliomas: 47.6% (10 of 21) in WHO grade IV gliomas and 22.2% (two of nine) in WHO grade III gliomas, whereas WHO grade II and I gliomas showed virtually no gCSCs. CONCLUSIONS: This trend of stage-by-stage increase of gCSCs in gliomas showed statistical significance by chi-square test linear-by-linear association. We prove that the rates of existence of gCSCs increase proportionally as the WHO grades of gliomas rise.

Skin-Whitening Effect of a Callus Extract of Nelumbo nucifera Isolate Haman.

The sacred lotus (Nelumbo nucifera Gaertn. Isolate Haman, in the family Nelumbonaceae) used in this study originated from the Haman region of Korea, and lotus seeds dating back to the Goryeo Dynasty (650-760 years ago) were accidentally discovered. Lotus is known to possess antioxidant, anti-inflammatory, and soothing properties. Instead of using the lotus alone, we obtained extracts using Haman region lotus-derived callus (HLC), which allowed for a controlled, quantitative, and infinite supply. Based on the reported effects of the lotus, we formulated a hypothesis to investigate the skin-whitening effect of the HLC extract (HLCE). The HLCE was first obtained by extraction with distilled water and using 5% propanediol as a solvent and subsequently verified for the whitening effect (melanin content tests) using mammalian cells in vitro. Its efficacy at the molecular level was confirmed through real-time polymerase chain reaction (PCR) using melanin-related genes. Furthermore, clinical trials with 21 volunteers confirmed the significant whitening effect of cosmetics containing the HLCE. In conclusion, we found that the HLCE not only has anti-inflammatory, antioxidant, and skin-soothing properties but also plays an essential role in skin whitening. Therefore, we propose that the HLCE has the potential to become a new raw material for the cosmetic industry.

Radiation Therapy for Recurrent or Residual Pituitary Macroadenoma Invading Extrasellar Structures.

PURPOSE: This study aimed to evaluate the efficacy of radiation therapy (RT) for recurrent or residual pituitary macroadenoma (PMA) invading extrasellar regions. MATERIALS AND METHODS: Patients from 2000 to 2020 who received RT with conventional fractionation for recurrent or residual PMA were included. The patients were divided according to the type of tumor [functioning (fx) or non-fx] and the aim of RT (salvage RT alone, immediate postoperative RT, delayed postoperative RT). Local and biochemical failure-free rates (FFR) were calculated using the Kaplan-Meier method. RESULTS: With a median follow up of 82 months (IQR; 42-132 months), 36 patients treated with conventional RT (total 45-54 Gy in 1.8 or 2 Gy per fraction) for recurrent or residual PMA were analyzed. The 10-year local FFRs after RT for non-fx and fx tumor were 100% and 74.4%, respectively (p=0.047). In the immediate postoperative RT group, the 10-year local FFR was 100%, which was higher than the 90% FFR for salvage RT alone or 80% FFR for the delayed postoperative RT group (overall p=0.043, immediate vs. salvage; p=0.312, immediate vs. delayed; p=0.072). The local FFR was compared according to size of tumor with a cut-off value of 4 cm, and there was no significant difference (10-year local FFR 100% vs. 84.7% for >4 cm vs. <4 cm, p=0.320). The extents of extrasellar region invasion were not predictive of local failure after RT. We found no grade ≥3 acute toxicities or newly developed visual impairments as a late toxicity of RT. CONCLUSION: Conventional RT is safe and effective for the local control of recurrent or residual PMA. Our data suggest that immediate postoperative RT can be beneficial in recurrent or residual PMA, although further studies to evaluate risk factors of treatment failure in terms of treatment and disease characteristics are required.

Tissue Niche Miniature of Glioblastoma Patient Treated with Nano-Awakeners to Induce Suicide of Cancer Stem Cells.

Patient-specific cancer therapies can evolve by vitalizing the mother tissue-like cancer niche, cellular profile, genetic signature, and drug responsiveness. This evolution has enabled the elucidation of a key mechanism along with development of the mechanism-driven therapy. After surgical treatment, glioblastoma (GBM) patients require prompt therapy within 14 days in a patient-specific manner. Hence, this study approaches direct culture of GBM patient tissue (1 mm diameter) in a microchannel network chip. Cancer vasculature-mimetic perfusion can support the preservation of the mother tissue-like characteristic signatures and microenvironment. When temozolomide and radiation are administered within 1 day, the responsiveness of the tissue in the chip reflected the clinical outcomes, thereby overcoming the time-consuming process of cell and organoid culture. When the tissue chip culture is continued, the intact GBM signature gets lost, and the outward migration of stem cells from the tissue origin increases, indicating a leaving-home effect on the family dismantle. Nanovesicle production using GBM stem cells enables self-chasing of the cells that escape the temozolomide effect owing to quiescence. The anti-PTPRZ1 peptide display and temozolomide loading to nanovesicles awakes cancer stem cells from the quiescent stage to death. This study suggests a GBM clinic-driven avatar platform and mechanism-learned nanotherapy for translation.

Crosstalk between Peroxisomal Activities and Nrf2 Signaling in Porcine Embryos.

Melatonin and phytanic acid (PA) are known to be involved in lipid metabolism and ß-oxidation, in which peroxisomal activities also significantly participate. In addition, other studies have reported that the nuclear factor-erythroid-derived 2-like 2 (Nrf2 or NFE2L2) signaling pathway mediates lipid metabolism and its subsequent cascades. As these mechanisms are partially involved in porcine oocytes or embryonic development, we hypothesized that the factors governing these mechanisms could be interconnected. Therefore, we aimed to investigate possible crosstalk between peroxisomal activities and Nrf2 signaling in porcine embryos following melatonin and PA treatment. Porcine embryos were cultured for seven days after parthenogenetic activation, and subsequently treated with melatonin and PA, or injected with Pex19-targeted siRNAs. Real-time PCR, immunocytochemistry, and BODIPY staining were used to evaluate peroxisomal activities, Nrf2 signaling, and subsequent lipid metabolism. We found that melatonin/PA treatment enhanced embryonic development, whereas injection with Pex19-targeted siRNAs had the opposite effect. Moreover, melatonin/PA treatment upregulated peroxisomal activities, Nrf2 signaling, lipid metabolism, and mitochondrial membrane potentials, whereas most of these mechanisms were downregulated by Pex19-targeted siRNAs. Therefore, we suggest that there is a connection between the action of melatonin and PA and the Nrf2 signaling pathway and peroxisomal activities, which positively influences porcine embryonic development.

Efficacy and Cerebrospinal Fluid Rhinorrhea after Cabergoline Treatment in Patients with Bioactive Macroprolactinoma.

Predicting dopamine agonist resistance in patients with macroprolactinoma is essential for clinicians to prevent treatment failure and subsequent complications such as medication-induced cerebrospinal fluid (CSF) rhinorrhea. We evaluated the features of patients with cabergoline resistance and CSF rhinorrhea in patients with prolactinomas with prolactin levels ≥1000 ng/mL. A total of 140 patients who were newly diagnosed with prolactinoma secreting only prolactin ≥1000 ng/mL and treated with cabergoline for the first time were included in this study. Based on the hormonal and radiologic response of the prolactinoma, the patients were divided into responders and non-responders. Non-responders (36/140, 25.8%) included a higher number of patients receiving hormone replacement than responders (responders, n (%) = 12(11.5) vs. non-responders = 13(36.1), p = 0.001). In propensity score matching analysis, patients who developed CSF rhinorrhea presented more frequent hormone deficiency than responders regardless of initial cabergoline dose. Hormone deficiency was associated with a greater odds ratio for the risk of non-responders (adjusted odds ratio = 5.13, 95% CI 1.96-13.46, p = 0.001). Cabergoline was effective in bioactive macroprolactinoma. Furthermore, initial cabergoline dose was not significantly associated with long-term responsiveness and development of CSF rhinorrhea but the hypopituitarism was independently associated with an increased risk of cabergoline resistance and CSF rhinorrhea.

Influence of the Amount of Fresh Specimen on the Isolation of Tumor Mesenchymal Stem-Like Cells from High-Grade Glioma.

PURPOSE: A critical indicator of the overall survival of patients with high-grade glioma is the successful isolation of tumor mesenchymal stem-like cells (tMSLCs), which play important roles in glioma progression. However, attempts to isolate tMSLCs from surgical specimens have not always been successful, and the reasons for this remain unclear. Considering that the amount of surgical high-grade glioma specimens varies, we hypothesized that larger surgical specimens would be better for tMSLC isolation. MATERIALS AND METHODS: We assessed 51 fresh, high-grade glioma specimens and divided them into two groups according to the success or failure of tMSLC isolation. The success of tMSLC isolation was confirmed by plastic adherence, presenting antigens, tri-lineage differentiation, and non-tumorigenicity. Differences in characteristics between the two groups were tested using independent two sample t-tests, chi-square tests, or Kaplan-Meier survival analysis. RESULTS: The mean specimen weights of the groups differed from each other (tMSLC-negative group: 469.9±341.9 mg, tMSLC positive group: 546.7±618.9 mg), but the difference was not statistically significant. The optimal cut-off value of specimen weight was 180 mg, and the area under the curve value was 0.599. CONCLUSION: Our results suggested a minimum criterion for specimen collection, and found that the specimen amount was not deeply related to tMSLC detection. Collectively, our findings imply that the ability to isolate tMSLCs is determined by factors other than the specimen amount.

Ambient carbon monoxide exposure and elevated risk of mortality in the glioblastoma patients: A double-cohort retrospective observational study.

An increasing number of studies indicate air pollutants infiltrate into the brain. We aimed to find the association of cumulative air pollution exposure in the main body of primary brain tumor: glioblastoma (GBM). In this double-cohort, retrospective analysis study with a protocol, we compared the health effect of air pollution on the GBM patients from the SEER (Surveillance, Epidemiology, and End Results Program) in 27 U.S. counties from 10 states and GBM patients of Severance cohort of Korea. From 2000 to 2015, 10621 GBM patients of the SEER were individually evaluated for the cumulative average exposure for each pollutant, and 9444 (88.9%) mortality events were reported. From 2011 to 2018, 398 GBM patients of the Severance with the same protocol showed 259 (65.1%) mortality events. The multi-pollutant models show that the association level of risk with CO is increased in the SEER (HR 1.252; 95% CI 1.141-1.373) with an increasing linear trend of relative death rate in the spline curve. The Severance GBM data showed such a statistically significant result of the health impact of CO on GBM patients. The overall survival gain of the less exposure group against CO was 2 and 3 months in the two cohorts. Perioperative exposure to CO may increase the risk of shorter survival of GBM patients of the SEER and the Severance cohort.