scholarly journals YK-4-279 Attenuates Progression of Pre-Existing Pigmented Lesions to Nodular Melanoma in a Mouse Model

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 143
Author(s):  
Lee Huang ◽  
Yougang Zhai ◽  
Cristian D. Fajardo ◽  
Deborah Lang
Keyword(s):  
Mouse Model ◽  
Tumor Progression ◽  
Delay Group ◽  
Control Group ◽  
Treatment Model ◽  
Tumor Initiation ◽  
Small Molecule Drug ◽  
Pigmented Lesions ◽  
Pigmented Lesion ◽  
Significant Block

More options are needed for the effective treatment of melanoma. In a previous study, we discovered the small molecule drug YK-4-279 almost completely inhibited tumor progression in the BrafCA;Tyr-CreERT2;Ptenflox/flox transgenic mouse model. YK-4-279 had no effect on tumor initiation but blocked progression of invasive melanoma. Our current study was designed as a treatment model, where YK-4-279 was administered during pigmented lesion formation. The study design included the use of three groups: (1) a control group that received only DMSO without a drug (MOCK), (2) mice following our prior studies with YK-4-279 administered at the time of tumor induction (YK-4-279), and (3) mice treated during tumor initiation (YK-4-279 delay). While the MOCK mice had progression of tumors, both YK-4-279 and YK-4-279 delay groups had a significant block or delay of progression. The majority of mice in the YK-4-279 groups had a block of progression, while the YK-4-279 delay group had either a partial block (60% in male mice or 29% in females) or a delay in disease progression in females (28 days in controls to 50 days in YK-4-279 delay group). Here, we demonstrate that YK-4-279 has a significant impact on blocking or delaying tumor progression in a pre-clinical treatment model of melanoma.

scholarly journals Protective Effects of Polyphenol Enriched Complex Plants Extract on Metabolic Dysfunctions Associated with Obesity and Related Nonalcoholic Fatty Liver Diseases in High Fat Diet-Induced C57BL/6 Mice

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 302
Author(s):  
Ahtesham Hussain ◽  
Jin Sook Cho ◽  
Jong-Seok Kim ◽  
Young Ik Lee
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
Mouse Model ◽  
High Fat Diet ◽  
Liver Diseases ◽  
Liver Weight ◽  
Control Group ◽  
High Fat ◽  
Herbal Formulation ◽  
Plants Extract

Background: Currently, obesity is a global health challenge due to its increasing prevalence and associated health risk. It is associated with various metabolic diseases, including diabetes, hypertension, cardiovascular disease, stroke, certain forms of cancer, and non-alcoholic liver diseases (NAFLD). Objective: The aim of this study to evaluate the effects of polyphenol enriched herbal complex (Rubus crataegifolius/ellagic acid, Crataegus pinnatifida Bunge/vitexin, chlorogenic acid, Cinnamomum cassiaa/cinnamic acid) on obesity and obesity induced NAFLD in the high-fat diet (HFD)-induced obese mouse model. Methods: Obesity was induced in male C57BL/6 mice using HFD. After 8 weeks, the mice were treated with HFD+ plants extract for 8 weeks. Body weight, food intake weekly, and blood sugar level were measured. After sacrifice, changes in the treated group’s liver weight, fat weight, serum biochemical parameters, hormone levels, and enzyme levels were measured. For histological analysis, tissues were stained with hematoxylin-eosin (H&E) and Oil Red-O. Results: Our results showed that the herbal complex ameliorated body weight and liver weight gain, and decreased total body fat in HFD-fed animals. Post prandial blood glucose (PBG) and fasting blood glucose (FBG) were lower in the herbal complex-treated group than in the HFD control group. Additionally, herbal formulation treatment significantly increased HDL levels in serum and decreased TC, TG, AST, ALT, deposition of fat droplets in the liver, and intima media thickness (IMT) in the aorta. Herbal complex increased serum adiponectin and decreased serum leptin. Herbal complex also increased carnitine palmityl transferase (CPT) activity and significantly decreased enzyme activity of beta-hydroxy beta methyl glutamyl-CoA (HMG-CoA) reductase, and fatty acid synthase (FAS). Conclusions: The results of this study demonstrated that the herbal complex is an effective herbal formulation in the attenuation of obesity and obesity-induced metabolic dysfunction including NAFLD in HFD-induced mouse model.

Pathological Alternations of Mediastinal Fat-Associated Lymphoid Cluster and Lung in a Streptozotocin-Induced Diabetic Mouse Model

2020 ◽  
pp. 1-14
Author(s):  
Yaser H.A. Elewa ◽  
Osamu Ichii ◽  
Teppei Nakamura ◽  
Yasuhiro Kon
Keyword(s):  
Endothelial Cells ◽  
Lung Injury ◽  
Mouse Model ◽  
Immune Cells ◽  
Inflammatory Markers ◽  
Inflammatory Marker ◽  
Diabetic Mouse ◽  
Control Group ◽  
Injury Progression

Diabetes is a devastating global health problem and is considered a predisposing factor for lung injury progression. Furthermore, previous reports of the authors revealed the role of mediastinal fat-associated lymphoid clusters (MFALCs) in advancing respiratory diseases. However, no reports concerning the role of MFALCs on the development of lung injury in diabetes have been published. Therefore, this study aimed to examine the correlations between diabetes and the development of MFALCs and the progression of lung injury in a streptozotocin-induced diabetic mouse model. Furthermore, immunohistochemical analysis for immune cells (CD3+ T-lymphocytes, B220+ B-lymphocytes, Iba1+ macrophages, and Gr1+ granulocytes), vessels markers (CD31+ endothelial cells and LYVE-1+ lymphatic vessels “LVs”), and inflammatory markers (TNF-α and IL-5) was performed. In comparison to the control group, the diabetic group showed lung injury development with a significant increase in MFALC size, immune cells, LVs, and inflammatory marker, and a considerable decrease of CD31+ endothelial cells in both lung and MFALCs was observed. Furthermore, the blood glucose level showed significant positive correlations with MFALCs size, lung injury, immune cells, inflammatory markers, and LYVE-1+ LVs in lungs and MFALCs. Thus, we suggest that the development of MFALCs and LVs could contribute to lung injury progression in diabetic conditions.

scholarly journals Protective Effects of Korean Herbal Remedy against Airway Inflammation in an Allergic Asthma by Suppressing Eosinophil Recruitment and Infiltration in Lung

Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 6
Author(s):  
Soyon Yoon ◽  
Seokcheon Song ◽  
Jae Woo Shin ◽  
Sini Kang ◽  
Hye Young Kim ◽  
...  
Keyword(s):  
Mouse Model ◽  
Allergic Asthma ◽  
Lung Tissue ◽  
Oral Delivery ◽  
Herbal Remedy ◽  
Periodic Acid ◽  
Lymphoid Cells ◽  
Lung Epithelial Cells ◽  
Eosinophil Infiltration ◽  
Control Group

The increasing prevalence of allergic asthma has become the world’s major health issue. Current treatments for allergic asthma focus on treating symptoms, while permanent cures still remain undiscovered. In this study, we investigated the effect of Korean traditional herbal remedy, Pyunkang-tang (PGT)—composed of six plants—on asthma alleviation in a mouse model. The PGT mixture was orally gavaged to mice (PM group, 20 mg/mouse/day) from 7 days before sensitization with ovalbumin (OVA) (day −7). On day 0 and day 14, mice from OVA-control (n = 9) and PM group (n = 8) were sensitized with OVA and alum through intraperitoneal injection. On days 18~20, OVA was challenged to mice through nasal injection and sacrificed next day. Cell profile in lung tissue was analyzed by flow cytometry and RT-qPCR analysis, and the number of eosinophils and expression of siglec-F were significantly reduced in the PM group. Lung tissue was examined with hematoxylin and eosin (H&E) and Alcian blue/periodic acid–Schiff (AB-PAS) staining. Noticeably reduced eosinophil infiltration around bronchioles was displayed in the PM group compared to the OVA-control group. Furthermore, PGT-treated mice showed a significant reduction in IL-13 and a mild reduction in IL-5 in lungs. A decreasing tendency of IL-5/13 (+) CD4+ T cells and IL-13(+) innate lymphoid cells (ILCs) and a significant reduction in IL5(+) ILCs were also observed. When treating PGT on murine lung epithelial cells stimulated by papain, there was a significant reduction in IL-33 mRNA expression levels. Taken together, oral delivery of PGT successfully alleviated asthmatic responses provoked by OVA in a mouse model and could lead to novel therapies for allergic asthma.

Effects of GYDENPHY caspules on streptozotocin-induced type 1 diabetic in Swiss mouse model

2021 ◽  
Vol 25 (2) ◽  
pp. 24-32
Author(s):  
Trinh Thach Thi Nguyen ◽  
Duy Tuan Nguyen ◽  
Thanh Ha Tuan Nguyen ◽  
Thi Huong Lan Do ◽  
Hoang Ngan Nguyen
Keyword(s):  
Blood Glucose ◽  
Mouse Model ◽  
Glucose Concentration ◽  
Blood Glucose Concentration ◽  
Insulin Injection ◽  
Swiss Mouse ◽  
Hypoglycemic Effect ◽  
Control Group ◽  
Water Control

Objective: Evaluation the hypoglycemic effect of Gydenphy capsules on Streptozotocin-induced type 1 diabetic in Swiss mouse model. Methods: The type 1 diabetic model was established by intraperitoneal injections of Streptozocin 150mg/kg in Swiss mouse. Then, the Gydenphy were orally administered daily at a dose of 576 mg/kg/day or 1152 mg/kg/day in 10 days. Blood glucose concentration in the Gydenphy oral groups with that of water control group and the intraperitoneal insulin injection group was compared. Results: Blood glucose concentration in the groups using Gydenphy (dose576 mg/kg/24h and dose 1152 mg/kg/24h) significal decreased compared to the distilled water group at (p <0.05 at the time of 4 hours, 8 hours; p <0.01 at the time of 3, 10 days). The hypoglycemic effect of Gydenphy at 576mg/kg/day and 1152 mg/kg/day at 4 hours, 8 hours and 3 days were inferior to insulin 0.1 UI/kg/day for glycemic control. However, the hypoglycemic effect ofGydenphy were equivalent to insulin after 10 consecutive days on treatment. Conclusion: Gydenphy capsules have hypoglycemic effects onStreptozotocin-induced type 1 diabetes in Swiss mouse model.

scholarly journals Familial, Social and Environmental Risk Factors in Autism: A Case-Control Study

2015 ◽  
Vol 40 (3) ◽  
pp. 113-117 ◽  
Author(s):  
A Jahan ◽  
SZR Rezina Parvin ◽  
D Bugum
Keyword(s):  
Risk Factors ◽  
Environmental Risk ◽  
Case Control Study ◽  
Significant Proportion ◽  
Case Control ◽  
Delay Group ◽  
Environmental Risk Factors ◽  
Control Group ◽  
Autism Group ◽  
Control Study

This case-control study was done to identify the correlation between the familial, social and environmental risk factors and autism. This hospital and specialized centre based study done from January 2002 to November, 2004. Thirty two children from the autism group and 14 children from the control group were enrolled. Mean age were 3.75 yrs. and 2.83 yrs. respectively. Significant proportion of children were in the highest birth orders, 68.8% in autism and 78.6% in the control group. Full term children were 96.9% and 92.9% respectively. 53.1% children in the autism and 57.1% in the normal speech delay group were born by cesarean sections. Higher education of parents in autism group was statistically significant (p<0.05). Too much watching TV, inadequate opportunity to mix with peers and inadequate interactive relationship with the family members in the early childhood were significantly (p= 0.001) related to the development of autism.Bangladesh Med Res Counc Bull 2014; 40 (3): 113-117

scholarly journals Establishment of a Mouse Model of Premature Ovarian Failure Using Consecutive Superovulation

2018 ◽  
Vol 51 (5) ◽  
pp. 2341-2358 ◽  
Author(s):  
Xiaowei Nie ◽  
Youjin Dai ◽  
Yuan Zheng ◽  
Dan Bao ◽  
Qin Chen ◽  
...  
Keyword(s):  
Mouse Model ◽  
Premature Ovarian Failure ◽  
Cell Apoptosis ◽  
Quantitative Polymerase Chain Reaction ◽  
Oocyte Quality ◽  
Ovarian Failure ◽  
Control Group ◽  
Mrna Levels ◽  
Primordial Follicles ◽  
Ovarian Aging

Background/Aims: This study investigated the effect of consecutive superovulation on the ovaries and established a premature ovarian failure (POF) model in mice. Methods: The mouse POF model was induced by 5-15 consecutive superovulation treatments with pregnant mare serum gonadotropin (PMSG), human chorionic gonadotropin (HCG) and prostaglandin F2α (PGF2α). Normal adult mice were compared with mice displaying natural ovarian aging. The following serum biochemical parameters were measured: including follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), estradiol (E2), inhibin B (INH B), malondialdehyde (MDA), total superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels. Follicles were counted using H&E staining. Levels of 8-hydroxyguanosine (8-OhdG), 4-hydroxynonenal (4-HNE), nitrotyrosine (NTY), anti-Mullerian hormone (AMH) and CDKN2A/ p16 (p16) were detected using immunohistochemical staining. Reactive oxygen species (ROS) levels were measured using dihydroethidium (DHE) staining. Cell apoptosis was detected using an in situ TUNEL fluorescence staining assay. Levels of proteins involved in ROS-related pathways and the p16 protein were detected using Western blotting. Sod1, Sod2 and Sod3 mRNA levels were detected using quantitative polymerase chain reaction (Q-PCR). Oocyte quality was evaluated using in vitro fertilization (IVF) and zygote culture. Results: Consecutive superovulation groups presented lower P, E2, SOD, GSH-Px and INH B levels, significantly higher FSH, LH, MDA and ROS levels, and significantly fewer primordial follicles compared with the control group. Consecutive superovulation groups presented significantly increased levels of Sod2, 8-OhdG, 4-HNE, NTY, significantly increased levels of the SIRT1 and FOXO1 proteins, significantly increased levels of the senescence-associated protein p16, as well as decreased AMH, Sod1 and Sod3 levels and increased granulosa cell apoptosis compared with the control group. Conclusion: Consecutive superovulation significantly decreased ovarian function and oocyte quality and increased oxidative stress and apoptosis in the ovary via a mechanism involving the p16 and SIRT1/FOXO1 signaling pathways. These findings suggest that consecutive superovulation may be used to establish a mouse model of ovarian aging.

Chemoprevention with Enalapril and Aspirin in Men1(+/T) Knockout Mouse Model

2018 ◽  
Vol 107 (3) ◽  
pp. 257-266 ◽  
Author(s):  
Jerena Manoharan ◽  
Volker Fendrich ◽  
Pietro Di Fazio ◽  
Carmen Bollmann ◽  
Silvia Roth ◽  
...  
Keyword(s):  
Mouse Model ◽  
Somatostatin Analogues ◽  
Control Group ◽  
Histopathological Analysis ◽  
Ki 67 ◽  
Chemopreventive Agents ◽  
Knockout Mouse Model ◽  
Angiotensin I Converting Enzyme ◽  
Significant Difference

Pancreatic neuroendocrine neoplasias (pNEN) are the most common cause of death in adult patients with multiple endocrine neoplasia type 1 (MEN1). So far, only few chemopreventive strategies (e.g., with somatostatin analogues) have been evaluated for MEN1 associated pNENs. In this experimental study on 75 Men1(+/T) knockout mice, the effect of aspirin (n = 25) and an inhibitor of angiotensin-I converting enzyme (enalapril, n = 25) compared to controls (n = 25) were evaluated as single chemopreventive strategies for pNENs after 6, 9, 12, 15, and 18 months. After each study period, mice were sacrificed and the resected pancreata were evaluated by histopathological analysis, immunostaining, and real-time PCR. PNEN size and number was measured. Aspirin and enalapril lead to a pNEN size reduction of 80% (167,518 vs. 838,876 µm2, p < 0.001) and 79% (174,758 vs. 838,876 µm2, p < 0.001) compared to controls. Furthermore, aspirin and enalapril treatment resulted in a significant reduction of the number of pNENs by 33%, (p = 0.04) and 41% (p = 0.002) respectively. The apoptosis marker caspase 3 revealed a higher positive expression in pNEN of treated Men1(+/T) mice. Immunostaining of VEGF in pNEN detected a downregulation of its expression in treated Men1(+/T) mice compared to the control group. REL A transcript was significantly downregulated in 18-months treated enalapril Men1(+/T) mice, but not in aspirin-treated Men1(+/T) mice. There was no significant difference in the Ki-67 index. Using a transgenic mouse model that imitates human MEN1, this study provides first evidence that aspirin and enalapril are effective chemopreventive agents that aid in the progression of pNENs.

scholarly journals Immunomodulatory Effects of Perioperative Dexmedetomidine in Ovarian Cancer: An In Vitro and Xenograft Mouse Model Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Seokyung Shin ◽  
Ki Jun Kim ◽  
Hye Jeong Hwang ◽  
Sewon Noh ◽  
Ju Eun Oh ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Mouse Model ◽  
Cell Viability ◽  
Nk Cell ◽  
Cell Activity ◽  
Tumor Burden ◽  
Control Group ◽  
Nk Cell Activity ◽  
Dexmedetomidine Infusion

BackgroundThe surgical stress response (SSR) causes immunosuppression which may cause residual tumor growth and micrometastasis after cancer surgery. We investigated whether dexmedetomidine affects cancer cell behavior and immune function in an ovarian cancer xenograft mouse model.MethodsThe effect of dexmedetomidine on cell viability and cell cycle was assessed using SK-OV-3 cells at drug concentrations of 0.5, 0.1, 5, and 10 µg mL-1. BALB/c nude mice were used for the ovarian cancer model with the Dexmedetomidine group (n=6) undergoing surgery with dexmedetomidine infusion and the Control group (n=6) with saline infusion for 4 weeks. Natural killer (NK) cell activity, serum proinflammatory cytokines, and cortisol were measured at predetermined time points and tumor burden was assessed 4 weeks after surgery.ResultsDexmedetomidine had no effect on cell viability or cell cycle. Following a sharp decrease on postoperative day (POD) 1, NK cell activity recovered faster in the Dexmedetomidine group with significant difference vs. the Control group on POD 3 (P=0.028). In the Dexmedetomidine group, cortisol levels were lower on POD 3 (P=0.004) and TNF-α levels were lower at 4 weeks after surgery (P&lt;0.001) compared to the Control group. The Dexmedetomidine group showed lower tumor burden at 4 weeks vs. the Control group as observed by both tumor weight (P&lt;0.001) and the in vivo imaging system (P=0.03).ConclusionsDexmedetomidine infusion may improve ovarian cancer surgery outcome by suppressing the SSR and stress mediator release. Further studies are needed to elucidate the mechanisms by which dexmedetomidine acts on cancer and immune cells.

scholarly journals Maternal factor PABPN1L is essential for maternal mRNA degradation during maternal-to-zygotic transition

2020 ◽  
Author(s):  
Ying Wang ◽  
Tianhao Feng ◽  
Xiaodan Shi ◽  
Siyu Liu ◽  
Zerui Wang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Large Scale ◽  
Mrna Degradation ◽  
Female Infertility ◽  
Control Group ◽  
Rna Seq ◽  
Cell Stage ◽  
Maternal Mrna ◽  
Maternal To Zygotic Transition ◽  
Group A

AbstractInfertility affects 10% - 15% of families worldwide. However, the pathogenesis of female infertility caused by abnormal early embryonic development is not clear. We constructed a mouse model (Pabpn1l -/-) simulating the splicing abnormality of human PABPN1L and found that the female was sterile and the male was fertile. The Pabpn1l -/- oocytes can be produced, ovulated and fertilized normally, but cannot develop beyond the 2-cell stage. Using RNA-Seq, we found a large-scale upregulation of RNA in Pabpn1l -/- MII oocytes. Of the 2401 transcripts upregulated in Pabpn1l-/- MII oocytes, 1523 transcripts (63.4%) were also upregulated in Btg4 -/- MII oocytes, while only 53 transcripts (2.2%) were upregulated in Ythdf2 -/- MII oocytes. We documented that transcripts in zygotes derived from Pabpn1l -/- oocytes have a longer poly(A) tail than the control group, a phenomenon similar to that in Btg4-/- mice. Surprisingly, the poly(A) tail of these mRNAs was significantly shorter in the Pabpn1l -/- MII oocytes than in the Pabpn1l +/+. These results suggest that PABPN1L is involved in BTG4-mediated maternal mRNA degradation, and may antagonize poly(A) tail shortening in oocytes independently of its involvement in maternal mRNA degradation. Thus, PABPN1L variants could be a genetic marker of female infertility.

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