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.

Gamma-Aminobutyric Acid in Rice Bran Extract Exerts Antistress Effects in Mouse Models with Depressive-Like Behaviors.

Various neurotransmitters are involved in regulating stress systems. In this study, we investigated the effects of gamma-aminobutyric acid-rich rice bran extract (GRBe) in mice stressed by forced swimming and tail suspension tests. Four weeks of oral administration of GRBe (500-2000 mg/kg) reduced the levels of dopamine and corticosterone in the blood and brain while increasing serotonin levels. GRBe was involved not only in stress but also in regulating sleep and obesity-related genes. Modern society experiences diverse and tense lives because of urbanization and informatization, which cause excessive stress due to complicated interpersonal relationships, heavy work burden, and fatigue from the organized society. High levels of stress cause psychological instability and disrupt the balance in the autonomic nervous system, which maintains the body's equilibrium, resulting in cardiovascular and cerebrovascular diseases, hormonal imbalances, and sleep disorders. Therefore, our results suggest that GRBe is a useful substance that can relieve tension by ultimately influencing a depressive-like state by lowering the levels of neuronal substances, hormones, and cytokines involved in stress and sleep disorders.

Phf7 has impacts on the body growth and bone remodeling by regulating testicular hormones in male mice.

PHD finger protein 7 (Phf7) is a member of the PHF family proteins, which plays important roles in spermiogenesis. Phf7 is expressed in the adult testes and its deficiency causes male infertility. In this study, we tried to find the causal relationship between Phf7 deficiency and reduced growth retardation which were found in null knock-out (Phf7-/-) mice. Phf7-/- mice were born normally in the Mendelian ratio. However, the Phf7-/- males showed decreased body weight gain, bone mineral density, and bone mineral content compared to those in wild-type (WT) mice. Histological analysis for tibia revealed increased number of osteoclast cells in Phf7-/- mice compared with that in WT mice. When we analyzed the expressions for marker genes for the initial stage of osteoclastogenesis, such as receptor activator of nuclear factor kappa B (Rank) in tibia, there was no difference in the mRNA levels between Phf7-/- and WT mice. However, the expression of tartrate-resistant acid phosphatase (Trap), a mature stage marker gene, was significantly higher in Phf7-/- mice than in WT mice. In addition, the levels of testosterone and dihydrotestosterone (DHT), more potent and active form of testosterone, were significantly reduced in the testes of Phf7-/- mice compared to those in WT mice. Furthermore, testicular mRNA levels for steroidogenesis marker genes, namely Star, Cyp11a1, Cyp17a1 and 17ß-hsd, were significantly lower in Phf7-/- mice than in WT mice. In conclusion, these results suggest that Phf7 deficiency reduces the production of male sex hormones and thereby impairs associated bone remodeling.

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.

Repeated intratracheal instillation of whole-cigarette smoke condensate to assess lung damage in a rat model.

Cigarette smoke induces an inflammatory response in the lungs by recruiting inflammatory cells, leading to lung diseases such as lung cancer, chronic obstructive pulmonary disease, and pulmonary fibrosis. Existing inhalation exposure methods for assessing the adverse effects of cigarette smoke require expensive equipment and are labor-intensive. Therefore, we attempted to develop a novel method to assess these adverse effects using intratracheal instillation (ITI) of whole cigarette smoke condensate (WCSC). The WCSC (0, 5, 10, or 20 mg/mL) was administered by ITI once daily for 6 or 12 days using an automatic video instillator. Repeated WCSC ITI increased the lung weight, and monocyte chemoattractant protein-1 (MCP-1), neutrophil, and lymphocyte levels within bronchoalveolar lavage fluid compared to the control. In the histopathological analysis of the lung tissue, a mild inflammatory response was observed in the 6 and 12 days 20 mg/mL WCSC exposure groups. The genome-wide RNA-seq expression patterns revealed that inflammatory and immune response-related genes, such as the chemokine signaling pathway, Th1/Th2 cell differentiation, and cytokine-cytokine receptor interaction, were employed following WCSC exposure. In addition, MCP-1 was time-dependent and increased in the 10 mg/mL exposure group compared to the control group. These results suggested that the WCSC might induce the potential pulmonary inflammatory response. Furthermore, we proposed that ITI may be a rapid and effective method of evaluating the adverse effects of WCSC within a short exposure period (less than 2 weeks), and it can be used to evaluate cigarette inhalation toxicity studies as an alternative method.

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.

Oxygen consumption rate to evaluate mitochondrial dysfunction and toxicity in cardiomyocytes.

The increase in the types and complexity of diseases has led to significant advances in diagnostic techniques and the availability of effective therapies. Recent studies have focused on the role of mitochondrial dysfunction in the pathogenesis of cardiovascular diseases (CVDs). Mitochondria are important organelles in cells that generate energy. Besides the production of adenosine triphosphate (ATP), the energy currency of cells, mitochondria are also involved in thermogenesis, control of intracellular calcium ions (Ca2+), apoptosis, regulation of reactive oxygen species (ROS), and inflammation. Mitochondrial dysfunction has been implicated in several diseases including cancer, diabetes, some genetic diseases, and neurogenerative and metabolic diseases. Furthermore, the cardiomyocytes of the heart are rich in mitochondria due to the large energy requirement for optimal cardiac function. One of the main causes of cardiac tissue injuries is believed to be mitochondrial dysfunction, which occurs via complicated pathways which have not yet been completely elucidated. There are various types of mitochondrial dysfunction including mitochondrial morphological change, unbalanced levels of substances to maintain mitochondria, mitochondrial damage by drugs, and mitochondrial deletion and synthesis errors. Most of mitochondrial dysfunctions are linked with symptoms and diseases, thus we focus on parts of mitochondrial dysfunction about fission and fusion in cardiomyocytes, and ways to understand the mechanism of cardiomyocyte damage by detecting oxygen consumption levels in the mitochondria.

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.

Yuja Juice and Concentrate Enhance Immunomodulating Effects via Increasing Immune-Related Cytokines in RAW264.7 Cells and Mouse Splenocytes.

Good immunity is highly valued in modern society. Although yuja's efficacy in immunity enhancement has been elucidated, there have been few studies on its role. In this study, we investigate the immune enhancement activity of yuja juice extracts (YJEs) and yuja concentrate extracts (YCEs). The immunoregulatory potencies of YJE and YCE were examined by determining cell viability and the expression of cytokines and immune-related molecules in RAW264.7 cells and mouse primary splenocytes. YJE and YCE induced the production of inducible nitric oxide synthase and cytokines (IL-10, IL-4, IL-6, and IFN-γ) at 1000 µg/mL concentration in RAW 264.7 cells. In addition, in mice that were orally administered 3000 or 2000 mg/kg concentrations of YJE or YCE, immune-related cytokines in splenocytes were boosted to levels higher than those in control mice. Importantly, no liver toxicity was observed at all doses. Thus, our results suggest that compounds present in YJEs and YCEs represent novel natural immune-modulatory substances.

Antitumor Effects of Dietary Compounds.

Cancer is reported to be a major cause of death worldwide, accounting for 10 million in 2020 based on 19 [...].

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.

Is navigation beneficial for transforaminal endoscopic lumbar foraminotomy? A preliminary comparison study with fluoroscopic guidance.

PURPOSE: The primary purpose of this study was to determine radiation exposure of the surgeon during transforaminal endoscopic lumbar foraminotomy (TELF). Secondary purpose of this study was to compare clinical and radiologic outcomes between TELF under C-arm fluoroscopic guidance (C-TELF) and O-arm navigation-guided TELF (O-TELF). METHODS: The author reviewed patients' medical records who underwent TELF at our institute from June 2015 to November 2022. A total of 40 patients were included (18 patients with C-TELF and 22 with O-TELF). Basic demographic data were collected. Preoperative/postoperative visual analog scale (VAS) and Oswestry Disability Index (ODI) were recorded at the outpatient clinic. Radiologic features were compared on X-rays at each follow-up. The degree of foraminal expansion was measured/compared through MRI. In the C-TELF group, the amount of exposure was calculated with a dosimeter. RESULTS: Average surgeon's effective dose in the C-TELF group was 0.036 mSv. In the case of the O-TELF group, there was no radiation exposure during operation. However, the operation time in the O-TELF group was about 37 min longer than that in the C-TELF group. There were significant improvements in VAS/ODI after operation in both groups. Complications were identified in three patients. CONCLUSION: O-TELF showed similarly favorable clinical and radiologic outcomes to C-TELF in lumbar foraminal stenosis, including complication rate. Compared to C-TELF, O-TELF has an advantage of not wearing a lead apron since the operator is not exposed to radiation. However, the operation time was longer with O-TELF due to O-arm setting time. Because there are pros and cons, the choice of surgical method depends on the surgeon's preference.

Bibliometric analysis and description of research trends on transforaminal full-endoscopic approach on the spine for the last two-decades.

OBJECTIVE: The study aims to assess the current development status of transforaminal full-endoscopic spine surgery (TFES) by exploring and analyzing the published literature to obtain an overview of this field and discover the evolution and emerging topics that are underrepresented. METHODS: Using Bibliometrix, CiteSpace, and VOSviewer, we analyzed the bibliometric data selected from the Web of Science Core Collection between January 2002 and November 2022. The descriptive and evaluative analyses of authors, institutes, countries, journals, keywords, and references are compiled. The quantity of research productivity was measured by the number of publications that were published. A quality indicator was thought to be the number of citations. In the bibliometric analysis of authors, areas, institutes, and references, we calculated and ranked the research impact by various metrics, such as the h-index and m-index. RESULTS: A total of 628 articles were identified in the field of TFES by the 18.73% annual growth rate of research on the subject from 2002 to 2022, constituting the documents are by 1961 authors affiliated with 661 institutions in 42 countries or regions and published in 117 journals. The USA (n = 0.20) has the highest international collaboration rate, South Korea has the highest H-index value (h = 33), and China is ranked as the most productive country (n = 348). Brown univ., Tongji univ., and Wooridul Spine represented the most productive institutes ranked by the number of publications. Wooridul Spine Hospital demonstrated the highest quality of paper publication. The Pain Physician had the highest h-index (n = 18), and the most cited journal with the earliest publication year in the area of FEDS is Spine (t = 1855). CONCLUSION: The bibliometric study showed a growing trend of research on transforaminal full-endoscopic spine surgery over the past 20 years. It has shown a significant increase in the number of authors, institutions, and international collaborating countries. South Korea, the United States, and China dominate the related areas. A growing body of evidence has revealed that TFES has leapfrogged from its infancy stage and gradually entered a mature development stage.

Full-Endoscopic Lumbar Discectomy Approach Selection: A Systematic Review and Proposed Algorithm.

STUDY DESIGN: A systematic review of the literature to develop an algorithm formulated by key opinion leaders. OBJECTIVE: This study aimed to analyze currently available data and propose a decision-making algorithm for full-endoscopic lumbar discectomy for treating lumbar disc herniation (LDH) to help surgeons choose the most appropriate approach [transforaminal endoscopic lumbar discectomy (TELD) or interlaminar endoscopic lumbar discectomy (IELD)] for patients. SUMMARY OF BACKGROUND DATA: Full-endoscopic discectomy has gained popularity in recent decades. To our knowledge, an algorithm for choosing the proper surgical approach has never been proposed. MATERIALS AND METHODS: A systematic review of the literature using PubMed and MeSH terms was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Patient samples included patients with LDH treated with full-endoscopic discectomy. The inclusion criteria were interventional research (randomized and nonrandomized trials) and observation research (cohort, case-control, case series). Exclusion criteria were case series and technical reports. The criteria used for selecting patients were grouped and analyzed. Then, an algorithm was generated based on these findings with support and reconfirmation from key expert opinions. Data on overall complications were collected. Outcome measures included zone of herniation, level of herniation, and approach (TELD or IELD). RESULTS: In total, 474 articles met the initial screening criteria. The detailed analysis identified the 80 best-matching articles; after applying the inclusion and exclusion criteria, 53 articles remained for this review. CONCLUSIONS: The proposed algorithm suggests a TELD for LDH located in the foraminal or extraforaminal zones at upper and lower levels and for central and subarticular discs at the upper levels considering the anatomic foraminal features and the craniocaudal pathology location. An IELD is preferred for LDH in the central or subarticular zones at L4/L5 and L5/S1, especially if a high iliac crest or high-grade migration is found.

ZBTB7A suppresses glioblastoma tumorigenesis through the transcriptional repression of EPB41L5.

Glioblastoma multiforme (GBM), the most aggressive and malignant glioma, has a poor prognosis. Although patients with GBM are treated with surgery, chemotherapy, and radiation therapy, GBM is highly resistant to treatment, making it difficult and expensive to treat. In this study, we analyzed the Gene Expression Profiling Interactive Analysis dataset, the Cancer Genome Atlas dataset, and Gene Expression Omnibus array data. ZBTB7A (also called FBI1/POKEMON/LRF) was found to be highly expressed in low-grade glioma but significantly downregulated in patients with GBM. ZBTB7A is a transcription factor that plays an important role in many developmental stages, including cell proliferation. The activation of epithelial-mesenchymal transition (EMT) is a key process in cancer progression and metastasis. Erythrocyte membrane protein band 4.1 like 5 (EPB41L5) is an essential protein for EMT progression and metastasis in various types of cancer. We found that ZBTB7A depletion in U87 cells induced GBM progression and metastasis. Based on RNA sequencing data, ZBTB7A directly binds to the promoter of the EPB41L5 gene, reducing its expression and inhibiting GBM progression. We demonstrated that ZBTB7A dramatically inhibits GBM tumor growth through transcriptional repression of EPB41L5. Thus, both ZBTB7A and EPB41L5 may be potential biomarkers and novel therapeutic targets for GBM treatment. Overall, we discovered the role of a novel tumor suppressor that directly inhibits GBM progression (ZBTB7A) and identified EPB41L5 as a therapeutic target protein for patients with GBM.

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.

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.

Transforaminal Endoscopic Decompression for Foraminal Stenosis: Single-Arm Meta-Analysis and Systematic Review.

OBJECTIVE: The objective of the study was to conduct a single-arm meta-analysis and comprehensive systematic review to identify the efficacy and safety of transforaminal endoscopic surgery for the treatment of lumbar foraminal stenosis (LFS). METHODS: The meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. The PubMed, Web of Science, and Embase databases were searched from inception to February 20, 2022. Primary research results were visual analog scale scores, Oswestry Disability Index scores, MacNab criterion scores, and reported adverse events. Subgroup analyses were performed on the primary outcome to evaluate the potential effects of several clinical factors that affected the results. RESULTS: Of the 2020 studies identified, 9 met the inclusion criteria, and 316 participants were eligible for meta-analysis. The meta-analysis results found that transforaminal endoscopic surgery for the treatment of LFS was associated with a significant improvement in postoperative 12-month clinical indicators: 8 studies reported improvements in visual analog scale scores: -5.38, Oswestry Disability Index scores: -40.44, and MacNab criterion scores: odds ratio = 0.86; 8 studies reported 11.53% adverse events occurred in a total of 295 patients, and the most commonly reported event was transient postoperative dysesthesia, which occurred in 26 patients in a total of 6 studies with 240 patients (10.83%). CONCLUSIONS: Transforaminal endoscopic surgery positively affects postoperative LFS patients' clinical indicators; however, high-level literature with randomized controlled trials is needed to confirm this technique's applicability in LFS.