Cordycepin Enhanced Therapeutic Potential of Gemcitabine against Cholangiocarcinoma via Downregulating Cancer Stem-Like Properties.

Cordycepin, a valuable bioactive component isolated from Cordyceps militaris, has been reported to possess anti-cancer potential and the property to enhance the effects of chemotherapeutic agents in various types of cancers. However, the ability of cordycepin to chemosensitize cholangiocarcinoma (CCA) cells to gemcitabine has not yet been evaluated. The current study was performed to evaluate the above, and the mechanisms associated with it. The study analyzed the effects of cordycepin in combination with gemcitabine on the cancer stem-like properties of the CCA SNU478 cell line, including its anti-apoptotic, migratory, and antioxidant effects. In addition, the combination of cordycepin and gemcitabine was evaluated in the CCA xenograft model. The cordycepin treatment significantly decreased SNU478 cell viability and, in combination with gemcitabine, additively reduced cell viability. The cordycepin and gemcitabine co-treatment significantly increased the Annexin V+ population and downregulated B-cell lymphoma 2 (Bcl-2) expression, suggesting that the decreased cell viability in the cordycepin+gemcitabine group may result from an increase in apoptotic death. In addition, the cordycepin and gemcitabine co-treatment significantly reduced the migratory ability of SNU478 cells in the wound healing and trans-well migration assays. It was observed that the cordycepin and gemcitabine cotreatment reduced the CD44highCD133high population in SNU478 cells and the expression level of sex determining region Y-box 2 (Sox-2), indicating the downregulation of the cancer stem-like population. Cordycepin also enhanced oxidative damage mediated by gemcitabine in MitoSOX staining associated with the upregulated Kelch like ECH Associated Protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) expression ratio. In the SNU478 xenograft model, co-administration of cordycepin and gemcitabine additively delayed tumor growth. These results indicate that cordycepin potentiates the chemotherapeutic property of gemcitabine against CCA, which results from the downregulation of its cancer-stem-like properties. Hence, the combination therapy of cordycepin and gemcitabine may be a promising therapeutic strategy in the treatment of CCA.

Mitochondrial transplantation exhibits neuroprotective effects and improves behavioral deficits in an animal model of Parkinson's disease.

Mitochondria are essential organelles for cell survival that manage the cellular energy supply by producing ATP. Mitochondrial dysfunction is associated with various human diseases, including metabolic syndromes, aging, and neurodegenerative diseases. Among the diseases related to mitochondrial dysfunction, Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by dopaminergic neuronal loss and neuroinflammation. Recently, it was reported that mitochondrial transfer between cells occurred naturally and that exogenous mitochondrial transplantation was beneficial for treating mitochondrial dysfunction. The current study aimed to investigate the therapeutic effect of mitochondrial transfer on PD in vitro and in vivo. The results showed that PN-101 mitochondria isolated from human mesenchymal stem cells exhibited a neuroprotective effect against 1-methyl-4-phenylpyridinium, 6-hydroxydopamine and rotenone in dopaminergic cells and ameliorated dopaminergic neuronal loss in the brains of C57BL/6J mice injected 30 â€‹mg/kg of methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneally. In addition, PN-101 exhibited anti-inflammatory effects by reducing the expression of pro-inflammatory cytokines in microglial cells and suppressing microglial activation in the striatum. Furthermore, intravenous mitochondrial treatment was associated with behavioral improvements during the pole test and rotarod test in the MPTP-induced PD mice. These dual effects of neuroprotection and anti-neuroinflammation support the potential for mitochondrial transplantation as a novel therapeutic strategy for PD.

Fludioxonil induces cardiotoxicity via mitochondrial dysfunction and oxidative stress in two cardiomyocyte models.

Fludioxonil (Flu) is a phenylpyrrole fungicide and is currently used in over 900 agricultural products globally. Flu possesses endocrine-disrupting chemical-like properties and has been shown to mediate various physiological and pathological changes, such as apoptosis and differentiation, in diverse cell lines. However, the effects of Flu on cardiomyocytes have not been studied so far. The present study investigated the effects of Flu on mitochondria in AC16 human cardiomyocytes and H9c2 rat cardiomyoblasts. Flu decreased cell viability in a water-soluble tetrazolium assay and mediated morphological changes suggestive of apoptosis in AC16 and H9c2 cells. We confirmed that annexin V positive cells were increased by Flu through annexin V/propidium iodide staining. This suggests that the decrease in cell viability due to Flu may be associated with increased apoptotic changes. Flu consistently increased the expression of pro-apoptotic markers such as Bcl-2-associated X protein (Bax) and cleaved-caspase 3. Further, Flu reduced the oxygen consumption rate (OCR) in AC16 and H9c2 cells, which is associated with decreased mitochondrial membrane potential (MMP) as observed through JC-1 staining. In addition, Flu augmented the production of mitochondrial reactive oxygen species, which can trigger oxidative stress in cardiomyocytes. Taken together, these results indicate that Flu induces mitochondrial dysregulation in cardiomyocytes via the downregulation of the OCR and MMP and upregulation of the oxidative stress, consequently resulting in the apoptosis of cardiomyocytes. This study provides evidence of the risk of Flu toxicity on cardiomyocytes leading to the development of cardiovascular diseases and suggests that the use of Flu in agriculture should be done with caution and awareness of the probable health consequences of exposure to Flu.

Gastrointestinal Bleeding in Extracorporeal Membrane Oxygenation Patients: A Comprehensive Analysis of Risk Factors and Clinical Outcomes.

Background: Extracorporeal membrane oxygenation (ECMO) is an intervention for severe heart and lung failure; however, it poses the risk of complications, including gastrointestinal bleeding (GIB). Comprehensive analyses of GIB in patients undergoing ECMO are limited, and its impact on clinical outcomes remains unclear. Methods: This retrospective study included 484 patients who received venovenous and venoarterial ECMO between January 2015 and December 2022. Data collected included patient characteristics, laboratory results, GIB details, and interventions. Statistical analyses were performed to identify risk factors and assess the outcomes. Results: GIB occurred in 44 of 484 patients (9.1%) who received ECMO. Multivariable analysis revealed that older age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01-1.06; p=0.0130) and need to change the ECMO mode (OR, 3.74; 95% CI, 1.75-7.96; p=0.0006) were significant risk factors for GIB, whereas no association was found with antiplatelet or systemic anticoagulation therapies during ECMO management. Half of the patients with GIB (22/44, 50%) underwent intervention, with endoscopy as the primary modality (19/22, 86.4%). Patients who underwent ECMO and developed GIB had higher rates of mortality (40/44 [90.9%] vs. 262/440 [59.5%]) and ECMO weaning failure (38/44 [86.4%] vs. 208/440 [47.3%]). Conclusion: GIB in patients undergoing ECMO is associated with adverse outcomes, including increased risks of mortality and weaning failure. Even in seemingly uncomplicated cases, it is crucial to avoid underestimating the significance of GIB.

Outcomes of Extracorporeal Membrane Oxygenation in COVID-19: A Single-Center Study.

Background: Coronavirus disease 2019 (COVID-19) can lead to acute respiratory failure, which frequently necessitates invasive mechanical ventilation and extracorporeal membrane oxygenation (ECMO). However, the limited availability of ECMO resources poses challenges to patient selection and associated decision-making. Consequently, this retrospective single-center study was undertaken to evaluate the characteristics and clinical outcomes of patients with COVID-19 receiving ECMO. Methods: Between March 2020 and July 2022, 65 patients with COVID-19 were treated with ECMO and were subsequently reviewed. Patient demographics, laboratory data, and clinical outcomes were examined, and statistical analyses were performed to identify risk factors associated with mortality. Results: Of the patients studied, 15 (23.1%) survived and were discharged from the hospital, while 50 (76.9%) died during their hospitalization. The survival group had a significantly lower median age, at 52 years (interquartile range [IQR], 47.5-61.5 years), compared to 64 years (IQR, 60.0-68.0 years) among mortality group (p=0.016). However, no significant differences were observed in other underlying conditions or in factors related to intervention timing. Multivariable analysis revealed that the requirement of a change in ECMO mode (odds ratio [OR], 366.77; 95% confidence interval [CI], 1.92-69911.92; p=0.0275) and the initiation of continuous renal replacement therapy (CRRT) (OR, 139.15; 95% CI, 1.95-9,910.14; p=0.0233) were independent predictors of mortality. Conclusion: Changes in ECMO mode and the initiation of CRRT during management were associated with mortality in patients with COVID-19 who were supported by ECMO. Patients exhibiting these factors require careful monitoring due to the potential for adverse outcomes.

Risk for Esophageal Cancer Based on Lifestyle Factors-Smoking, Alcohol Consumption, and Body Mass Index: Insight from a South Korean Population Study in a Low-Incidence Area.

Esophageal cancer constitutes a global public health challenge. However, South Korean population-specific information on the association of lifestyle (smoking, alcohol consumption, and obesity status) with esophageal cancer risk is sparse. This nested case-control study analyzed the Korean national health screening cohort data (2002-2019) of 1114 patients with esophageal cancer and 4456 controls (1:4 propensity-score matched for sex, age, income, and residential region). Conditional and unconditional logistic regression analyses, after adjustment for multiple covariates, determined the effects of lifestyle factors on esophageal cancer risk. Smoking and alcohol consumption increased the esophageal cancer risk (adjusted odds ratio [95% confidence interval]: 1.37 [1.15-1.63] and 1.89 [1.60-2.23], respectively). Overweight (body mass index [BMI] ≥ 23 to <25 kg/m2), obese I (BMI ≥ 25 to <30 kg/m2), or obese II (BMI ≥ 30 kg/m2) categories had reduced odds of esophageal cancer (0.76 [0.62-0.92], 0.59 [0.48-0.72], and 0.47 [0.26-0.85], respectively). In the subgroup analyses, the association of incident esophageal cancer with smoking and alcohol consumption persisted, particularly in men or those aged ≥55 years, whereas higher BMI scores remained consistently associated with a reduced esophageal cancer likelihood across all age groups, in both sexes, and alcohol users or current smokers. Underweight current smokers exhibited a higher propensity for esophageal cancer. In conclusion, smoking and alcohol drinking may potentially increase the risk, whereas weight maintenance, with BMI ≥ 23 kg/m2, may potentially decrease the risk, for esophageal cancer in the South Korean population. Lifestyle modification in the specific subgroups may be a potential strategy for preventing esophageal cancer.

Use of cutting-edge RNA-sequencing technology to identify biomarkers and potential therapeutic targets in canine and feline cancers and other diseases.

With the growing interest in companion animals and the rapidly expanding animal healthcare and pharmaceuticals market worldwide. With the advancements in RNA-sequencing (RNA-seq) technology, it has become a valuable tool for understanding biological processes in companion animals and has multiple applications in animal healthcare. Historically, veterinary diagnoses and treatments relied solely on clinical symptoms and drugs used in human diseases. However, RNA-seq has emerged as an effective technology for studying companion animals, providing insights into their genetic information. The sequencing technology has revealed that not only messenger RNAs (mRNAs) but also non-coding RNAs (ncRNAs) such as long ncRNAs and microRNAs can serve as biomarkers. Based on the examination of RNA-seq applications in veterinary medicine, particularly in dogs and cats, this review concludes that RNA-seq has significant potential as a diagnostic and research tool. It has enabled the identification of potential biomarkers for cancer and other diseases in companion animals. Further research and development are required to maximize the utilization of RNA-seq for improved disease diagnosis and therapeutic targeting in companion animals.

Complete genome sequence of seed-transmitted soybean yellow mottle mosaic virus from soybeans in Korea.

Soybean yellow mottle mosaic virus (SYMMV), a member of the genus Gammacarmovirus, remains poorly understood in terms of its transmission pathway. This study reveals the complete genome sequence of a seed-transmitted isolate, ST-HB56, contributing to the understanding of SYMMV's ecological dynamics.

Complete genome sequence of soybean geminivirus A in soybean in Korea.

Soybean geminivirus A (SGVA), a member of the family Geminiviridae, was detected in a survey of early-stage soybean. The complete genome sequence of SGVA isolate Habin was determined, revealing its characteristics and similarity to Korean and Chinese isolates. This study contributes to understanding the impact of SGVA on soybean production.

Genetically engineered neural stem cells expressing cytosine deaminase and interferon-beta enhanced T cell-mediated antitumor immunity against gastric cancer in a humanized mouse model.

AIMS: Gastric cancer (GC) is an invasive, fatal disease with a poor prognosis. Gene-directed enzyme prodrug therapy via genetically engineered neural stem cells (GENSTECs) has been widely studied in various malignancies, such as breast, ovarian, and renal cancer. In this study, the human neural stem cells expressing cytosine deaminase and interferon beta (HB1.F3.CD.IFN-ß) cells were applied to convert non-toxic 5-fluorocytosine to cytotoxic 5-fluorouracil and secrete IFN-ß. MATERIALS AND METHODS: Human lymphokine-activated killer cells (LAKs) were generated by stimulating human peripheral blood mononuclear cells (PBMCs) by interleukin-2, and we evaluated the cytotoxic activity and migratory ability of LAKs co-cultured with GNESTECs or their conditioned media in vitro. A GC-bearing human immune system (HIS) mouse model was generated by transplanting human PBMCs followed by subcutaneous engraftment of MKN45 cells in NSG-B2m mice to evaluate the involvement of T cell-mediated anti-cancer immune activity of GENSTECs. KEY FINDINGS: In vitro studies showed the presence of HB1.F3.CD.IFN-ß cells facilitated the migration ability of LAKs to MKN45 cells and activated their cytotoxic potential. In MKN45-xenografted HIS mice, treatment with HB1.F3.CD.IFN-ß cells resulted in increased cytotoxic T lymphocyte (CTL) infiltration throughout the tumor, including the central area. Moreover, the group treated to HB1.F3.CD.IFN-ß showed increased granzyme B expression in the tumor, eventually enhancing the tumor-killing potential of CTLs and significantly delaying tumor growth. SIGNIFICANCE: These results indicate that the HB1.F3.CD.IFN-ß cells exert anti-cancer effects on GC by facilitating the T cell-mediated immune response, and GENSTECs are a promising therapeutic strategy for GC.

First Report of Olive Mild Mosaic Virus in Imported Tulips (Tulipa gesneriana) in Korea.

Tulip cultivation in Korea primarily uses imported bulbs due to the absence of domestic production. To ensure safety and sustainability, Korean authorities have implemented strict phytosanitary measures for five viruses: arabis mosaic virus, tobacco necrosis virus, tobacco ringspot virus, tomato black ring virus, and tomato bushy stunt virus. In April 2021, 86 tulip plants presented symptoms such as chlorotic mottle, mosaic, streak, stripe, yellowing of the leaves, and color breaking on flowers. These samples were collected to investigate the incidence of viruses in four Korean provinces (Gangwon, Gyeongbuk, Gyeongnam, and Chungnam). The leaves and petals from each individual sample (10 mg each) were pooled and ground using liquid nitrogen. Total RNA was extracted using a Maxwell® 16 LEV Plant RNA Kit (Promega, Madison, USA). A cDNA library was constructed using TruSeq Standard Total RNA with Ribo - Zero (Illumina, San Diego, USA) and sequenced on an Illumina NovaSeq 6000 platform (Macrogen, Seoul, Korea) with 100-bp paired-end reads. Trinity software identified tulip breaking virus (TBV), tulip virus X (TVX), and lily symptomless virus (LSV), which are known to occur in Korea (Bak et al. 2023) by de novo assembly of 628 million reads into 498,795 contigs. The contigs were annotated as previously described (Bak et al. 2022). Moreover, a contig (ON758350) related to olive mild mosaic virus (OMMV; genus Alphanecrovirus, family Tombusviridae) was identified through BLASTn analysis. This contig had a 99.27% nucleotide (nt) identity to OMMV PPO-L190209 (KU641010), which was assembled from 201,346 reads and spanned 3,713 bp. To confirm the presence of OMMV, a primer pair (5'-GAATGTCTGGCGTTAAGCG-3'/5'-GTGTCCTGCGCATCATACAC-3') was designed to amplify a 797-bp fragment of the coat protein gene. In RT-PCR, 31.4% (27/86) of samples were positive for OMMV and coinfected with TBV or TBV+LSV. Coinfection with TBV led to chlorotic mottling and stripes, whereas triple coinfection with TBV+LSV produced distinct yellow streaks and mosaic within the lesion boundaries. In contrast, solely TBV infection did not produce such symptoms. The samples infected with OMMV were exclusively collected from Gangwon and Gyeongnam. In each province, an RT-PCR amplicon was cloned, and subsequently sequenced (Bioneer, Daejeon, Korea). The obtained sequences were named CC (OM243091) and GS (OM243092), and they shared 98.6% and 98.9% identity with PPO-L190209 (KU641010), respectively. A bioassay was conducted using a leaf infected with OMMV CC and TBV to inoculate 13 indicator species in triplicate, including Capsicum annuum, Chenopodium amaranticolor, C. quinoa, Cucumis sativus, Nicotiana benthamiana, N. clevelandii, N. glutinosa, N. occidentalis, N. rustica, N. tabacum, Solanum lycopersicum, Tetragonia tetragonioides, and Tulipa gesneriana. The RT-PCR revealed positivity only for OMMV in the upper leaves of N. clevelandii, while all other species were negative with no symptoms. To our knowledge, this is the first report of OMMV occurring in tulips grown from imported bulbs in Korea, with no other known natural hosts such as olive tree (Cardoso et al. 2004), spinach (Gratsia et al. 2012), and corn salad (Verdin et al. 2018). The Korean OMMV isolates exhibited a high nt identity with the foreign isolate, and the samples were collected from farms that rely entirely on bulb imports for cultivation. These suggest that the outbreak of OMMV was likely caused by imported bulbs.

Chemical Pleurodesis Using Tetracycline for the Management of Postoperative Pneumothorax Recurrence.

Background: Although there is no obvious recommendation for the management of pneumothorax recurrence after surgery, chemical pleurodesis with tetracycline has been applied as a significant treatment approach. The objective of this study was to evaluate the effectiveness of chemical pleurodesis with tetracycline for the management of postoperative recurrence of primary spontaneous pneumothorax (PSP). Methods: We retrospectively analyzed patients who underwent video-assisted thoracic surgery (VATS) as therapy for PSP at Hallym University Sacred Heart Hospital from January 2010 to December 2016. Patients who had ipsilateral recurrence after surgery were included in this study. Patients who underwent pleural drainage with chemical pleurodesis were compared with patients who only underwent pleural drainage. Results: In total, 932 patients who underwent VATS for PSP were analyzed, and ipsilateral recurrence after surgery occurred in 67 patients (7.1%). The treatment modalities for recurrence after surgery were observation (n=12), pleural drainage alone (n=16), pleural drainage with chemical pleurodesis (n=34), and repeated VATS (n=5). Eight of the 16 patients (50 %) treated with pleural drainage alone had recurrence again, while 15 of the 34 patients (44.1%) treated with pleural drainage and chemical pleurodesis experienced further recurrence. Chemical pleurodesis with tetracycline did not show a meaningful difference in the re-recurrence rate in comparison with pleural drainage alone (p=0.332). Conclusion: Chemical pleurodesis with tetracycline for the management of postoperative recurrence of PSP was not effective. Further research is required to identify alternative drugs that can significantly decrease the re-recurrence rate.

Effects of CCN6 overexpression on the cell motility and activation of p38/bone morphogenetic protein signaling pathways in pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancer types that is highly resistant to conventional treatments, such as chemotherapy and radiotherapy. As the demand for more effective therapeutics for PDAC treatment increases, various approaches have been studied to develop novel targets. The cellular communication network (CCN) family is a matricellular protein that modulates various cellular functions, including cell adhesion, proliferation, migration, and invasiveness. Despite this, little is known about the role of CCN6 in PDAC. The current study investigated the role of CCN6 in PDAC by generating CCN6-overexpressing PANC-1 cells (PANC-1-CCN6) by infecting lentivirus particles containing CCN6. PANC-1-CCN6 induces cell viability and tumorigenesis than PANC-1 cells with empty vector (control). The PANC-1-CCN6 formed more colonies, and the size of spheroids increased compared to the control. The upregulation of CCN6 enhances the expression of bone morphogenetic proteins (BMPs) genes and the upregulation of p38 mitogen-activated protein kinases (MAPKs). In PANC-1-CCN6 cells, the levels of N-cadherin, VEGF, and Snail expression were higher than the control, while E-cadherin expression was lower, which is associated with upregulation of epithelial-to-mesenchymal transition (EMT). Consistent with the changes in EMT-related proteins in PANC-1-CCN6, the migratory ability and invasiveness were enhanced in PANC-1-CCN6. Xenografted PANC-1-CCN6 in immunocompromised mice exhibited accelerated tumor growth than the control group. In immunohistochemistry (IHC), the PANC-1-CCN6 xenografted tumor showed an increased positive area of PCNA and Ki-67 than the control. These results suggest that CCN6 plays a tumorigenic role and induces the metastatic potential by the p38 MAPK and BMPs signaling pathways. Although the role of CCN6 has been introduced as an antitumor factor, there was evidence of CCN6 acting to cause tumorigenesis and invasion in PANC-1.

Effects of once-weekly dulaglutide on juvenile type 2 diabetes mellitus and obesity in Korea: a pilot study.

PURPOSE: We sought to investigate the effects and side effects of once-weekly dulaglutide treatment for type 2 diabetes mellitus (T2DM) in patients <18 years of age in Korea. METHODS: : From the Eulji University Hospital database, we identified all patients <18 years of age diagnosed with T2DM and treated with dulaglutide from January 1, 2017, to July 31, 2022. RESULTS: We identified 5 patients <18 years of age treated with dulaglutide for T2DM management. Their mean (standard deviation [SD]) age was 16.6 (0.5) years. Four (80%) patients were female. The mean (SD) body mass index was 29.4 (5.1) kg/m2, and the mean (SD) age at diagnosis was 15.2 (1.6) years. Four patients had been treated previously with metformin alone or in combination with insulin. Four patients were treated with 1.5 mg of dulaglutide and one was treated with 0.75 mg of dulaglutide. The mean (SD) hemoglobin A1c concentrations at baseline, 3 months after treatment, and 1 year after treatment, respectively, were 10.0% (2.2%), 6.5% (1.5%), and 6.7% (1.4%), with significant differences. In addition, at baseline, 3 months after treatment, and 1 year after treatment, the mean (SD) body weight values were 79.7 (13.3) kg, 80.2 (14.0) kg, and 81.1 (15.3) kg, with no significant difference. CONCLUSION: Use of once-weekly dulaglutide for juvenile T2DM ensures very good glycemic control, with few side effects and good adherence, indicating its potential as a promising therapeutic agent in this age group. Nationwide studies are warranted to confirm our results.

TGF-ß2 antisense oligonucleotide enhances T-cell mediated anti-tumor activities by IL-2 via attenuation of fibrotic reaction in a humanized mouse model of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, with high mortality and recurrence rate. In this study, we generated a human immune system mouse model by transplanting human peripheral blood mononuclear cells into NSG-B2m mice followed by xenografting AsPC-1 cells, after which we assessed the role of transforming growth factor-ß2 (TGF-ß2) in T-cell-mediated anti-tumor immunity. We observed that inhibiting the TGF-ß2 production by TGF-ß2 antisense oligonucleotide (TASO) combined with IL-2 delays pancreatic cancer growth. Co-treatment of TASO and IL-2 had little effect on the SMAD-dependent pathway, but significantly inhibited the Akt phosphorylation and sequentially activated GSK-3ß. Activation of GSK-3ß by TASO subsequently suppressed ß-catenin and α-SMA expression and resulted in attenuated fibrotic reactions, facilitating the infiltration of CD8 + cytotoxic T lymphocytes (CTLs) into the tumor. TGF-ß2 inhibition suppressed the Foxp3 + regulatory T-cells in peripheral blood and tumors, thereby enhancing the tumoricidal effects of CTLs associated with increased granzyme B and cleaved caspase-3. Moreover, changes in the T-cell composition in peripheral blood and at the tumor site by TASO and IL-2 induced the increase of pro-inflammatory cytokines such as IFN-γ and TNF-α and the decrease of anti-inflammatory cytokines such as TGF-ßs. These results indicate that the TGF-ß2 inhibition by TASO combined with IL-2 enhances the T-cell mediated anti-tumor immunity against SMAD4-mutated PDAC by modulating the tumor-associated fibrosis, suggesting that TASO in combination with IL-2 may be a promising immunotherapeutic intervention for PDAC.

Human platelet mitochondria improve the mitochondrial and cardiac function of donor heart.

Mitochondria transplantation emerges as an effective therapeutic strategy for ischemic-related diseases but the roles in the donor hearts for transplant remain unidentified. Here, we investigated whether the preservation of the donor heart with human platelet-derived mitochondria (pl-MT) could improve mitochondrial and cardiac function. Incubation with pl-MT resulted in the internalization of pl-MT and the enhancement of ATP production in primary cardiomyocytes. In addition, incubation of rat hearts with pl-MT ex vivo for 9 h clearly demonstrated pl-MT transfusion into the myocardium. Mitochondria isolated from the hearts incubated with pl-MT showed increased mitochondrial membrane potential and greater ATP synthase activity and citrate synthase activity. Importantly, the production of reactive oxygen species from cardiac mitochondria was not different with and without pl-MT incubation. Functionally, the heartbeat and the volume of coronary circulation perfusate were significantly increased in the Langendorff perfusion system and the viability of cardiomyocytes was increased from pl-MT hearts.Taken together, these results suggest that incubation with Pl-MT improves mitochondrial activity and maintains the cardiac function of rat hearts with prolonged preservation time. The study provides the proof of principle for pl-MT application as an enhancer of the donor heart.

Complete Genome Sequences of Two Apple Stem Grooving Viruses in Cnidium officinale in Korea.

We determined the whole-genome sequences of two apple stem grooving viruses (ASGV) detected in infected Cnidium officinale plants. The analyzed ASGV genomes were 6,494 nucleotides long and encoded two overlapping open reading frames. Phylogenetic analysis revealed the two ASGV isolates to be most closely related to the ASGV isolate Xinjiang-3.

Engineered adult stem cells: a promising tool for anti-cancer therapy.

Cancers are one of the most dreaded diseases in human history and have been targeted by numerous trials including surgery, chemotherapy, radiation therapy, and anti-cancer drugs. Adult stem cells (ASCs), which can regenerate tissues and repair damage, have emerged as leading therapeutic candidates due to their homing ability toward tumor foci. Stem cells can precisely target malicious tumors, thereby minimizing the toxicity of normal cells and unfavorable side effects. ASCs, such as mesenchymal stem cells (MSCs), neural stem cells (NSCs), and hematopoietic stem cells (HSCs), are powerful tools for delivering therapeutic agents to various primary and metastatic cancers. Engineered ASCs act as a bridge between the tumor sites and tumoricidal reagents, producing therapeutic substances such as exosomes, viruses, and anti-cancer proteins encoded by several suicide genes. This review focuses on various anti-cancer therapies implemented via ASCs and summarizes the recent treatment progress and shortcomings. [BMB Reports 2023; 56(2): 71-77].

Amurensin G Sensitized Cholangiocarcinoma to the Anti-Cancer Effect of Gemcitabine via the Downregulation of Cancer Stem-like Properties.

Cholangiocarcinoma (CCA) is a malignant biliary tract tumor with a high mortality rate and refractoriness to chemotherapy. Gemcitabine is an anti-cancer chemotherapeutic agent used for CCA, but the efficacy of gemcitabine in CCA treatment is limited, due to the acquisition of chemoresistance. The present study evaluated the chemosensitizing effects of Amurensin G (AMG), a natural sirtuin-1 inhibitor derived from Vitis amurensis, in the SNU-478 CCA cells. Treatment with AMG decreased the SNU-478 cell viability and the colony formation ability. Annexin V/ Propidium iodide staining showed that the AMG increased apoptotic death. In addition, AMG downregulated anti-apoptotic Bcl-2 expression, while upregulating pro-apoptotic cleaved caspase-3 expression. Treatment with AMG decreased the migratory ability of the cells in a wound healing assay and transwell migration assay. It was observed that AMG decreased the gemcitabine-induced increase in CD44highCD24highCD133high cell populations, and the expression of the Sox-2 protein was decreased by AMG treatment. Co-treatment of AMG with gemcitabine significantly enhanced the production of reactive oxygen species, as observed through mitochondrial superoxide staining, which might be associated with the downregulation of the Sirt1/Nrf2 pathway by AMG. These results indicate that AMG enhances the chemotherapeutic ability of gemcitabine by downregulating cancer stem-like properties in CCA cells. Hence, a combination therapy of AMG with gemcitabine may be an attractive therapeutic strategy for cholangiocarcinoma.

Overexpression of KiSS1 Induces the Proliferation of Hepatocarcinoma and Increases Metastatic Potential by Increasing Migratory Ability and Angiogenic Capacity.

Liver cancer has a high prevalence, with majority of the cases presenting as hepatocellular carcinoma (HCC). The prognosis of metastatic HCC has hardly improved over the past decade, highlighting the necessity for liver cancer research. Studies have reported the ability of the KiSS1 gene to inhibit the growth or metastasis of liver cancer, but contradictory research results are also emerging. We, therefore, sought to investigate the effects of KiSS1 on growth and migration in human HCC cells. HepG2 human HCC cells were infected with lentivirus particles containing KiSS1. The overexpression of KiSS1 resulted in an increased proliferation rate of HCC cells. Quantitative polymerase chain reaction and immunoblotting revealed increased Akt activity, and downregulation of the G1/S phase cell cycle inhibitors. A significant increase in tumor spheroid formation with upregulation of ß-catenin and CD133 was also observed. KiSS1 overexpression promoted the migratory, invasive ability, and metastatic capacity of the hepatocarcinoma cell line, and these effects were associated with changes in the expressions of epithelial mesenchymal transition (EMT)-related genes such as E-cadherin, N-cadherin, and slug. KiSS1 overexpression also resulted in dramatically increased tumor growth in the xenograft mouse model, and upregulation of proliferating cell nuclear antigen (PCNA) and Ki-67 in the HCC tumors. Furthermore, KiSS1 increased the angiogenic capacity by upregulation of the vascular endothelial growth factor A (VEGF-A) and CD31. Based on these observations, we infer that KiSS1 not only induces HCC proliferation, but also increases the metastatic potential by increasing the migratory ability and angiogenic capacity.