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1.
Cell Mol Life Sci ; 81(1): 38, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38214772

RESUMO

During in vitro culture, human pluripotent stem cells (hPSCs) often acquire survival advantages characterized by decreased susceptibility to mitochondrial cell death, known as "culture adaptation." This adaptation is associated with genetic and epigenetic abnormalities, including TP53 mutations, copy number variations, trisomy, and methylation changes. Understanding the molecular mechanisms underlying this acquired survival advantage is crucial for safe hPSC-based cell therapies. Through transcriptome and methylome analysis, we discovered that the epigenetic repression of CHCHD2, a mitochondrial protein, is a common occurrence during in vitro culture using enzymatic dissociation. We confirmed this finding through genetic perturbation and reconstitution experiments in normal human embryonic stem cells (hESCs). Loss of CHCHD2 expression conferred resistance to single cell dissociation-induced cell death, a common stress encountered during in vitro culture. Importantly, we found that the downregulation of CHCHD2 significantly attenuates the activity of Rho-associated protein kinase (ROCK), which is responsible for inducing single cell death in hESCs. This suggests that hESCs may survive routine enzyme-based cell dissociation by downregulating CHCHD2 and thereby attenuating ROCK activity. These findings provide insights into the mechanisms by which hPSCs acquire survival advantages and adapt to in vitro culture conditions.


Assuntos
Células-Tronco Embrionárias Humanas , Células-Tronco Pluripotentes , Humanos , Linhagem Celular , Repressão Epigenética , Variações do Número de Cópias de DNA , Células-Tronco Embrionárias Humanas/metabolismo , Diferenciação Celular , Sobrevivência Celular , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
2.
Breast Cancer Res ; 26(1): 65, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609935

RESUMO

BACKGROUND: Sentinel lymph node biopsy (SLNB) is recommended for patients with ductal carcinoma in situ (DCIS) undergoing mastectomy, given the concerns regarding upstaging and technical difficulties of post-mastectomy SLNB. However, this may lead to potential overtreatment, considering favorable prognosis and de-escalation trends in DCIS. Data regarding upstaging and axillary lymph node metastasis among these patients remain limited. METHODS: We retrospectively reviewed patients with DCIS who underwent mastectomy with SLNB or axillary lymph node dissection at Gangnam Severance Hospital between January 2010 and December 2021. To explore the feasibility of omitting SLNB, we assessed the rates of DCIS upgraded to invasive carcinoma and axillary lymph node metastasis. Binary Cox regression analysis was performed to identify clinicopathologic factors associated with upstaging and axillary lymph node metastasis. RESULTS: Among 385 patients, 164 (42.6%) experienced an invasive carcinoma upgrade: microinvasion, pT1, and pT2 were confirmed in 53 (13.8%), 97 (25.2%), and 14 (3.6%) patients, respectively. Seventeen (4.4%) patients had axillary lymph node metastasis. Multivariable analysis identified age ≤ 50 years (adjusted odds ratio [OR], 12.73; 95% confidence interval [CI], 1.18-137.51; p = 0.036) and suspicious axillary lymph nodes on radiologic evaluation (adjusted OR, 9.31; 95% CI, 2.06-41.99; p = 0.004) as independent factors associated with axillary lymph node metastasis. Among patients aged > 50 years and/or no suspicious axillary lymph nodes, only 1.7-2.3%) experienced axillary lymph node metastasis. CONCLUSIONS: Although underestimation of the invasive component was relatively high among patients with DCIS undergoing mastectomy, axillary lymph node metastasis was rare. Our findings suggest that omitting SLNB may be feasible for patients over 50 and/or without suspicious axillary lymph nodes on radiologic evaluation.


Assuntos
Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Humanos , Feminino , Biópsia de Linfonodo Sentinela , Carcinoma Intraductal não Infiltrante/cirurgia , Metástase Linfática , Neoplasias da Mama/cirurgia , Estudos Retrospectivos , Mastectomia
3.
Small ; : e2401364, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874055

RESUMO

Limited electrochemical stability windows of conventional carbonate-based electrolytes pose a challenge to support the Lithium (Li)- and manganese (Mn)-rich (LMR) high-voltage cathodes in rechargeable Li-metal batteries (LMBs). To address this issue, a novel localized high-concentration electrolyte (LHCE) composition incorporating LiPF6 and LiTFSI as dual-salts (D-LHCE), tailored for high-voltage (>4.6 Vvs.Li) operation of LMR cathodes in LMBs is introduced. 7Li nuclear magnetic resonance and Raman spectroscopy revealed the characteristics of the solvation structure of D-LHCE. The addition of LiPF6 provides stable Al-current-collector passivation while the addition of LiTFSI improves the stability of D-LHCE by producing a more robust cathode-electrolyte interphase (CEI) on LMR cathode and solid-electrolyte interphase (SEI) on Li-metal anode. As a result, LMR/Li cell, using the D-LHCE, achieved 72.5% capacity retention after 300 cycles, a significant improvement compared to the conventional electrolyte (21.9% after 100 cycles). The stabilities of LMR CEI and Li-metal SEI are systematically analyzed through combined applications of electrochemical impedance spectroscopy and distribution of relaxation times techniques. The results present that D-LHCE concept represents an effective strategy for designing next-generation electrolytes for high-energy and high-voltage LMB cells.

4.
Can Vet J ; 65(6): 553-558, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38827592

RESUMO

Gastrointestinal stromal tumors arising from gastric cardia are uncommon in dogs. A few studies have shown the effectiveness of tyrosine kinase inhibitors in the treatment of canine gastrointestinal stromal tumors, but no standardized protocols are currently available. An 11-year-old spayed female Maltese dog was diagnosed with a gastrointestinal stromal tumor using histopathological and immunohistochemical analyses. An adenosine triphosphate-based tumor chemosensitivity assay revealed that imatinib at lower concentrations had a stronger inhibitory effect than toceranib. Based on the results of the assay, the dog was treated with imatinib after surgery. After 28 mo of therapy, there was no recurrence of the tumor. Key clinical message: Adenosine triphosphate-based tumor chemosensitivity assays may help clinicians to select appropriate postoperative chemotherapeutic drugs for incompletely resected gastrointestinal stromal tumors in dogs.


Gestion réussie à la suite d'une résection incomplète d'une tumeur stromale gastro-intestinale à l'aide de l'imatinib basée sur un test de sensibilité tumorale à base d'adénosine triphosphate chez un chien. Les tumeurs stromales gastro-intestinales résultant du cardia gastrique sont rares chez le chien. Quelques études ont montré l'efficacité des inhibiteurs de la tyrosine kinase dans le traitement des tumeurs stromales gastrointestinales canines, mais aucun protocole standardisé n'est actuellement disponible. Une chienne maltaise stérilisée de 11 ans a reçu un diagnostic de tumeur stromale gastro-intestinale à l'aide d'analyses histopathologiques et immunohistochimiques. Un test de chimiosensibilité tumorale à base d'adénosine triphosphate a révélé que l'imatinib à des concentrations plus faibles avait un effet inhibiteur plus fort que le tocéranib. Sur la base des résultats du test, le chien a été traité avec de l'imatinib après l'opération. Après 28 mois de traitement, il n'y a eu aucune récidive de la tumeur.Message clinique clé :Les tests de chimiosensibilité tumorale à base d'adénosine triphosphate peuvent aider les cliniciens à sélectionner les médicaments chimiothérapeutiques postopératoires appropriés pour les tumeurs stromales gastro-intestinales incomplètement réséquées chez le chien.(Traduit par Dr Serge Messier).


Assuntos
Antineoplásicos , Doenças do Cão , Tumores do Estroma Gastrointestinal , Mesilato de Imatinib , Animais , Tumores do Estroma Gastrointestinal/veterinária , Tumores do Estroma Gastrointestinal/cirurgia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/patologia , Cães , Mesilato de Imatinib/uso terapêutico , Doenças do Cão/tratamento farmacológico , Doenças do Cão/cirurgia , Feminino , Antineoplásicos/uso terapêutico , Trifosfato de Adenosina/uso terapêutico , Indóis , Pirróis
5.
Vet Med (Praha) ; 68(2): 83-89, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38332765

RESUMO

A 10-year-old spayed female Pomeranian dog was referred for hepatic mass evaluation. Blood tests revealed mildly elevated alkaline phosphatase activities. Computed tomography revealed a mass with multiple nodules on the right hepatic medial lobe adjacent to the caudal vena cava; histopathology confirmed mixed hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Because of incomplete resection, adjuvant therapy was recommended. As tumour cells showed PDGFR-α, c-Kit, and FGFR1 overexpression, the anticancer effect of tyrosine kinase inhibitors was evaluated on the cells; toceranib was the most effective and was administered starting with an extra-labelled dose. The dog remained stable for 2.3 years with mild adverse effects. To our knowledge, this is the first successful clinical application of toceranib in a dog with mixed HCC-CC.

6.
Vet Med (Praha) ; 68(12): 477-482, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38303994

RESUMO

This case report follows a 10-year-old castrated male Miniature Schnauzer dog presented with a history of incomplete surgical resection of an oral malignant melanoma (amelanotic type) on the right mandible. Melanoma vaccine therapy was administered due to incomplete surgical resection, however, new masses were detected on the contralateral mandible and suspected pulmonary metastasis occurred at 2 weeks and 7 months, respectively, following the first melanoma vaccination. At the time of detecting the pulmonary metastasis, targeted chemotherapy was initiated with the owner's consent using imatinib (10 mg/kg/day, p.o.), a tyrosine kinase inhibitor (TKI). The patient did not show any significant adverse events related to both anticancer treatments. Three months following the first dose of imatinib, the absence of the suspected pulmonary metastatic nodules on radiography indicated complete remission. In conclusion, this report describes the achievement of clinical remission of suspected pulmonary metastatic oral malignant melanoma and an extension of survival time in a dog given a combination treatment of immunotherapy and tyrosine kinase inhibitor.

7.
Vet Med (Praha) ; 67(10): 544-551, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38716301

RESUMO

A 2-year-old, castrated, male Russian blue cat presented with acute dyspnoea, cyanosis, and lethargy. A thoracic radiography revealed a large cranial mediastinal mass; the computed tomography revealed caudal lobe atelectasis of the right lung with pericardial and pleural effusions. The cytodiagnostic tests revealed high-grade CD4+ CD8+ T-cell mediastinal lymphoma as clinical stage Vb; l-asparaginase-cyclophosphamide-doxorubicin-vincristine-prednisolone (l-CHOP)-based chemotherapy was initiated, following which the mass shrunk rapidly; 1 week after the initiation of chemotherapy, the appetite-related and respiratory symptoms improved dramatically, and the pleural and pericardial effusion resolved. The patient remains in complete remission three years after the initiation of the l-CHOP chemotherapy. Therefore, the accurate diagnosis and instantaneous initiation of chemotherapy may resolve life-threatening pleural and pericardial effusions in cats with high-grade aberrant T-cell mediastinal lymphoma.

8.
Vet Med (Praha) ; 67(8): 447-453, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-38716189

RESUMO

A ten-year-old indoor, castrated male Cardigan Welsh Corgi (Canis familiaris) presented with the chief complaints of chronic vomiting, retching, hypersalivation, and bilateral submandibular masses for two months. The systemic examinations, including serum chemistry, radiography, ultrasonography, and fluoroscopy, were unremarkable. A fine-needle aspiration revealed bilateral submandibular sialadenitis. Broad-spectrum antibiotics with phenobarbital were prescribed to alleviate the ptyalism. Thereafter, the left submandibular glands were normalised, and the right submandibular glands decreased to half their size. Three weeks later, the animal had an emergency visit because of a sudden left exophthalmos. Computed tomography and magnetic resonance imaging revealed enlarged left zygomatic and right mandibular salivary glands. The affected glands were surgically removed; the histopathologic examination confirmed non-septic sialadenitis, and the patient was finally diagnosed with idiopathic sialadenitis. Vomiting continued after the gland removal and the dog required a gradual increase in the phenobarbital dosage and an additional antiepileptic drug (potassium bromide) to manage the symptoms. The patient died eight months later from an unknown cause. This case report of bilateral submandibular sialadenitis concurrent with unilateral zygomatic sialadenitis in a Welsh Corgi dog suggests that when multiple salivary glands are involved, the response to anti-epileptic drugs and the prognosis is poor compared to that involving a single salivary gland.

9.
Vet Med (Praha) ; 67(11): 590-597, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38846793

RESUMO

A 5-year-old neutered male Shiba Inu dog presented with a history of oral bleeding, dysphagia, and depression for 3 weeks. The physical examination revealed a firm mass in the right caudal palatal region along the level of PM4-M2. On the computed tomography, the mass was round-to-oval in shape and 22 mm × 30 mm × 15 mm in size. The mass contained multiple bone attenuated materials with a palatal bone lysis of 4 mm × 6 mm. A complete resection of the mass was proposed; however, the owner declined due to the risk of complications associated with the radical surgery. Therefore, a palliative resection and biopsy of the mass were performed. On the histological examination, the mass was diagnosed as grade 2 multilobular tumour of bone (MTB). Since the mass was incompletely resected, adjuvant therapy was pursued along with targeted therapy using a tyrosine kinase inhibitor. The tumour cells showed overexpression of the receptor of tyrosine kinase for c-KIT, PDGFR-α, PDGFR-ß, and FGFR1 compared to normal tissue cells. Additionally, the cytotoxic effect of imatinib on the MTB cells was confirmed in vitro. Four weeks postoperatively, the administration of imatinib and carprofen was initiated and continued for 259 days. The patient maintained a good functional outcome for 306 days after the initial presentation.

10.
Vet Sci ; 11(6)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38922010

RESUMO

A 13-year-old spayed female cocker spaniel was presented with a 2-month history of swelling in several digits and intermittent hindlimb lameness. Radiographs revealed marked soft-tissue swelling and periosteal new bone formation without cortical bone destruction, characteristic of hypertrophic osteopathy (HO), in the distal parts of all extremities except for the right forelimb. However, no notable findings were detected in thoracic radiographs. An ultrasonography indicated cranial bladder wall thickening, which resolved following antibiotic therapy. Computed tomographic angiography identified a potential underlying cause as an aberrant right subclavian artery (ARSA) originating from the aortic arch, compressing the esophagus and causing mild esophageal cranial dilation to the aberrant vessel. No other intrathoracic or neoplastic lesions were observed. Gastrointestinal symptoms, such as regurgitation, were absent. Although an ARSA was likely the cause of HO, surgical correction was declined by the owner. To the best of our knowledge, this is the first reported case of HO concurrent with ARSA in dogs.

11.
Stem Cell Res ; 77: 103415, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38636267

RESUMO

Under hypoxia, hypoxia-inducible factor (HIF)-1 regulates hypoxia-inducible genes, such as vascular endothelial growth factor (VEGF) and its receptors VEGFR1 and VEGFR2. It is an oxygen-dependent transcriptional activator that plays a crucial role in tumor angiogenesis and mammalian embryo development. It is a heterodimeric protein comprising a constitutively expressed HIF-1ß subunit and the highly regulated HIF-1α subunits. Using CRISPR-Cas9 genome editing, we generated biallelic HIF-1α mutants in human induced pluripotent stem cells (hiPSCs). The HIF-1α homozygous-knockout hiPSCs retained their normal morphology, gene expression, and in vivo differentiation potential.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia , Células-Tronco Pluripotentes Induzidas , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Diferenciação Celular , Técnicas de Inativação de Genes , Hipóxia Celular , Sistemas CRISPR-Cas , Linhagem Celular , Edição de Genes , Animais
12.
Nutr Res Pract ; 18(3): 436-445, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38854472

RESUMO

BACKGROUND/OBJECTIVES: Breast cancer is considered a serious health issue worldwide and is influenced by risk factors, including physical inactivity and unhealthy diet. Myokines secreted by muscles during physical activity play a crucial role in cancer development and the immune system. Genistein (Gen), an isoflavone primarily in legumes, induces anti-cancer activity by regulating cancer stem cells (CSCs). Therefore, this study investigated the potential anti-cancer effect of a combination of myokine and Gen on the human breast cancer MCF-7 cells. MATERIALS/METHODS: MCF-7, a human breast cancer cell line, was used for in vitro study. The cell viability of MCF-7 cells was evaluated in response to treatment with myokines, irisin (Iri), oncostatin M (OSM), and Gen using the MTT assay. Clonogenic and sphere formation assays were used to evaluate the self-renewal capacity of breast CSCs. The mRNA expression levels of stem cell markers were analyzed in MCF-7 breast cancer cells. RESULTS: Administering Iri or OSM with Gen significantly inhibited the self-renewal capacity of MCF-7 cells. In addition, mRNA expression of breast CSC markers SOX2 and OCT4, which are characteristic of CSCs, was suppressed by both myokine and Gen. However, combining Iri or OSM with Gen was the most effective treatment. CONCLUSION: These results suggested that combining Iri or OSM with Gen has an additive effect on breast CSCs by regulating self-renewal capacity and expression of CSCs markers. Therefore, the combination of myokines and Gen may have the therapeutic potential for treating breast cancer and improving the quality of life of cancer patients.

13.
Toxins (Basel) ; 16(2)2024 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-38393162

RESUMO

Limited evidence suggests that stimulating adipose-derived stem cells (ASCs) indirectly promotes hair growth. We examined whether bee venom (BV) activated ASCs and whether BV-induced hair growth was facilitated by enhanced growth factor release by ASCs. The induction of the telogen-to-anagen phase was studied in mice. The underlying mechanism was investigated using organ cultures of mouse vibrissa hair follicles. When BV-treated ASCs were injected subcutaneously into mice, the telogen-to-anagen transition was accelerated and, by day 14, the hair weight increased. Quantitative polymerase chain reaction (qPCR) revealed that BV influenced the expression of several molecules, including growth factors, chemokines, channels, transcription factors, and enzymes. Western blot analysis was employed to verify the protein expression levels of extracellular-signal-regulated kinase (ERK) and phospho-ERK. Both the Boyden chamber experiment and scratch assay confirmed the upregulation of cell migration by BV. Additionally, ASCs secreted higher levels of growth factors after exposure to BV. Following BV therapy, the gene expression levels of alkaline phosphatase (ALP), fibroblast growth factor (FGF)-1 and 6, endothelial cell growth factor, and platelet-derived growth factor (PDGF)-C were upregulated. The findings of this study suggest that bee venom can potentially be utilized as an ASC-preconditioning agent for hair regeneration.


Assuntos
Venenos de Abelha , Animais , Camundongos , Venenos de Abelha/farmacologia , Venenos de Abelha/metabolismo , Proliferação de Células , Cabelo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Células-Tronco/metabolismo , Células Cultivadas
14.
Prev Med Rep ; 44: 102767, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38983449

RESUMO

Objective: The surge in vehicles has escalated traffic volume, leading to an upswing in traffic accidents and subsequent disorders. Complex symptoms often characterize post-traumatic syndrome from these accidents. Traditional Korean medicine (TKM), increasingly used in car insurance, forms a substantial part of treatment costs. However, the current system lacks explicit fee guidelines and approval criteria for non-reimbursable TKM procedures, relying heavily on practitioners' judgment without robust evidence-based decision-making. This scenario raises concerns about treatment appropriateness and transparency. We aim to explore physicians' perspectives on utilizing TKM in emergency medicine, their participation sentiments, and their session selection process post-traffic accident. Methods: We collected TKM practitioners' opinions regarding their role in clinical environment and involvement in treating patients after traffic accidents. The need for comprehensive and standardized protocols for the diagnosis, treatment, management, and prognosis of patients with post-traumatic syndrome is evident. Additionally, improvements that facilitate rational decision-making by medical consumers and protect the treatment rights of healthcare providers are necessary. Results has emphasized the importance of evidence-based decision-making, establishing appropriate fee structures and detailed criteria for non-reimbursable TKM-based procedures, and enhancing regulations for the reliability and transparency of TKM-based treatments in the context of car insurance. Results and conclusions: The perspective of healthcare providers directly involved in TKM-based treatments must be considered to maintain a sustainable vehicular insurance system, transcending administrative policy discourse. We highlighted the challenges and potential solutions for improving the effectiveness and appropriateness of TKM-based treatments in the context of car insurance.

15.
Biochem Biophys Rep ; 38: 101684, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38511188

RESUMO

Background: Regular physical activities reduce the growth of breast cancer, but research on the effects of steady exercise on metastasis and its mechanisms is limited. In this study, the effects of steady exercise on breast cancer metastasis and its possible mechanism were demonstrated. Methods: Experimental metastasis was induced after 8 weeks of steady exercise using a mouse model. Furthermore, one of the myokines, irisin, was studied to elucidate the effects of metastasis-regulating protein expression, and colony and sphere formation, which are cancer stem cell properties. Results: Low- and moderate-intensity exercise significantly reduced the number and volume of metastasized tumors. Among myokines, only irisin was significantly increased by steady exercise but decreased by a high-fat diet. In vitro studies, irisin significantly decreased the number of colonies and sphere formation. Irisin also inhibited cell migration and invasion and suppressed the malignancy of breast cancer cells by reducing the expression of vimentin, MMP-2, MMP-9, and HIF-1 and by increasing the expression of TIMP-1 and TIMP-2. Conclusion: Steady exercise modulates myokine secretions and among them, irisin suppresses breast cancer metastasis by decreasing self-renewal properties and invasion regulating protein expressions. Thus, regular exercise may be beneficial in the prevention of breast tumor metastasis.

16.
ACS Appl Mater Interfaces ; 16(8): 10307-10315, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38380594

RESUMO

The cost reduction and mass production of oxide-based solid electrolytes are critical for the commercialization of all-solid-state batteries. In this study, an environmentally friendly, low-cost, and high-density oxide-based Na superionic conductor-type solid electrolyte sheet was fabricated via a dry process without the use of any solvent. The polytetrafluoroethylene (PTFE), used as a binder, was transformed into thin thread-like structures via shear force, resulting in a flexible solid electrolyte sheet. The solid electrolyte powder quantity was limited to 50 wt % for fabricating a uniform green sheet via the wet process. However, when the dry process was employed for green sheet fabrication, the solid electrolyte powder quantity could be increased to values exceeding 95 wt %. Therefore, the green sheets produced by using the dry process demonstrated a higher density than those fabricated by using the wet process. The binder content and particle size affected the ionic conductivity of a solid electrolyte sheet fabricated via a dry process. The sheet obtained via the blending of 3 wt % PTFE binder with a solid electrolyte powder, finely ground using a planetary ball mill, which exhibited the highest total ionic conductivity of 1.03 mS cm-1.

17.
Front Vet Sci ; 11: 1392728, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38840628

RESUMO

Background: Hepatocellular carcinoma (HCC) is the most common malignant liver tumor in dogs. Although surgical resection is a major treatment option for canine HCC, there are no distinct strategies for unresectable tumor subtypes or adjuvant chemotherapy for tumors with positive margins. We aimed to establish and characterize novel HCC cell lines from canine patients. Methods: The cellular morphology, general growth features and tumorigenicity of the established cell lines were evaluated. We also examined the sensitivity of the cell lines to multi-target tyrosine kinase inhibitors (TKIs). Results: We established novel canine HCC cell lines from hepatic tumors and an additional kidney tumor of six canine patients. All cell lines showed colony forming and migratory ability. KU-cHCC-001 and KU-cHCC-001-Kidney, two cell lines exhibiting high epithelial-mesenchymal transition characteristics, showed tumorigenicity in xenografted mice. Toceranib, a veterinary TKI that targets vascular endothelial growth factor (VEGFR)/platelet-derived growth factor receptor (PDGFR)/c-kit, effectively inhibited the mitogen-activated protein kinase pathway and induced apoptosis. The established canine HCC cell lines showed greater sensitivity to toceranib than to sorafenib, a first-line treatment for human HCC targeting RAF/VEGFR/PDGFR. Sorafenib showed improved anti-tumor effects when co-treated with SCH772984, an extracellular signal-regulated kinase inhibitor. Conclusion: Our study suggests new therapeutic strategies for canine HCC, and these cell lines are valuable research materials for understanding HCC tumor biology in both humans and dogs.

18.
Environ Pollut ; 357: 124387, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38897275

RESUMO

Despite its reputation as one of the cleanest regions globally, recent studies have identified the presence of various persistent toxic substances (PTSs) in the environmental matrices collected from Svalbard. This study investigated the chronological distribution and potential sources of 81 PTSs in soils from the glacier foreland of Midtre Lovénbreen. Soil samples (n = 45) were categorized by age based on exposure to the atmosphere due to glacier retreat in July 2014 into five age groups: 80-100 years (n = 7), 60-80 years (n = 12), 40-60 years (n = 16), 20-40 years (n = 7), and <20 years (n = 3). Concentrations of polychlorinated biphenyls (PCBs, n = 32) in soils varied with age, ranging from 0.29 to 0.74 ng g-1 dw. In addition, the concentrations of polycyclic aromatic hydrocarbons (PAHs, n = 28), perylene, and alkyl-PAHs (n = 20) in soils ranged from 21 to 80 ng g-1 dw, 2.9-62 ng g-1 dw, and 73-420 ng g-1 dw, respectively. The concentrations of PTSs were observed to be greater in older soils. Principal component analysis revealed that PCBs in soils originated from various product sources. Positive matrix factorization modeling estimated the association of PAHs in soils with potential origins, such as diesel emissions, petroleum and coal combustion, and coal. Potential sources of PAHs were mainly coal in younger soils and diesel emissions and petroleum combustion in older soils. Alkyl-PAH compositions in the soil were similar to those of bituminous coal, with a noteworthy degree of weathering observed in older soils. The accumulation rate and flux of PTSs in soils exhibited compound-specific patterns, reflecting factors such as long-range transport, fate, origin, and recent inputs. These findings can serve as baseline data for protecting and preserving polar environments.


Assuntos
Monitoramento Ambiental , Camada de Gelo , Bifenilos Policlorados , Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Solo , Poluentes do Solo/análise , Solo/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Bifenilos Policlorados/análise , Camada de Gelo/química , Substâncias Perigosas/análise
19.
Heliyon ; 10(10): e31154, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38813210

RESUMO

In this study, we estimated the contributions of carbonate mineral weathering to dissolved inorganic carbon (DIC) and carbonate-derived DIC to autochthonous particulate organic carbon (POC) in two temperate Korean rivers. We combined stoichiometric and stable carbon isotopic approaches to calculate the contribution of autochthonous POC, considering diverse riverine DIC sources. We collected surface water samples from May 2016 to May 2018 and analyzed the major ion composition of rivers along with the concentrations and stable carbon isotopes of DIC. Our estimates showed that the relative abundances of carbonate mineral weathering (0.41 ± 0.11 in the Geum River and 0.43 ± 0.07 in the Seomjin River) were only slightly lower than those of silicate mineral weathering (0.59 ± 0.1 in the Geum River and 0.57 ± 0.07 in the Seomjin River). The resulting percentage contributions of DIC derived from the carbonate mineral weathering to riverine autochthonous POC, if we consider the additional DIC sources of atmospheric and soil-derived CO2, were 10 ± 3 % in the Geum River and 2 ± 1 % in the Seomjin River. The calculated annual fluxes of carbonate-derived DIC for 2016-2018 were 23.2 ± 0.3 Gg C yr-1 in the Geum River and 1.1 ± 0.4 Gg C yr-1 in the Seomjin River. Moreover, the calculated annual fluxes of carbonate-derived POC were 3.6 ± 0.5 Gg C yr-1 in the Geum River and 0.1 ± 0.7 Gg C yr-1 in the Seomjin River. Accordingly, our study provides the first insight into the contribution of carbonate-derived DIC to riverine autochthonous POC in small temperate Korean river systems, dominated by silicate rocks.

20.
NAR Genom Bioinform ; 6(2): lqae070, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38881577

RESUMO

Ribosomal DNA (rDNA) repeat units are organized into tandem clusters in eukaryotic cells. In mice, these clusters are located on at least eight chromosomes and show extensive variation in the number of repeats between mouse genomes. To analyze intra- and inter-genomic variation of mouse rDNA repeats, we selectively isolated 25 individual rDNA units using Transformation-Associated Recombination (TAR) cloning. Long-read sequencing and subsequent comparative sequence analysis revealed that each full-length unit comprises an intergenic spacer (IGS) and a ∼13.4 kb long transcribed region encoding the three rRNAs, but with substantial variability in rDNA unit size, ranging from ∼35 to ∼46 kb. Within the transcribed regions of rDNA units, we found 209 variants, 70 of which are in external transcribed spacers (ETSs); but the rDNA size differences are driven primarily by IGS size heterogeneity, due to indels containing repetitive elements and some functional signals such as enhancers. Further evolutionary analysis categorized rDNA units into distinct clusters with characteristic IGS lengths; numbers of enhancers; and presence/absence of two common SNPs in promoter regions, one of which is located within promoter (p)RNA and may influence pRNA folding stability. These characteristic features of IGSs also correlated significantly with 5'ETS variant patterns described previously and associated with differential expression of rDNA units. Our results suggest that variant rDNA units are differentially regulated and open a route to investigate the role of rDNA variation on nucleolar formation and possible associations with pathology.

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