Cancer cachexia-anorexia is a multi-organ metabolic syndrome characterized by anorexia and weight loss. Generally, such symptoms are a serious problem in cancer patients, adversely affecting chemotherapy success and survival rate. Cachexia has been reported to accompany up to 80% of gastrointestinal cancers, such as pancreatic, lung, and colon cancer, though it is relatively rare in lymphoma or breast cancer patients. It is also known that cancer-induced anorexia occurs independently of chemotherapy, although decreased appetite due to chemotherapy is well reported. In terms of pathoflammatory cytokines that are excessively increased by tumor tissues. Since the mechanism of cancer cachexia is not yet fully understood, there are currently no therapeutic agents or diagnostic markers to treat it. A recently published study identified a substance secreted from cancer cells that induces cancer anorexia, and the molecular mechanism causing the eating disorder was discovered. An increase in the expression of this substance has been shown to be statistically correlated with the symptoms of cachexia in cancer patients, and it is therefore expected to be applicable in the diagnosis and development of therapeutic agents for cancer cachexia. This review article aims to provide an overview of the key molecular mechanisms of the anorexia and tissue wasting caused by cancer cachexia.
Tenorio, Karine Isabela;Eyng, Cinthia;Duarte, Cristiane Regina do Amaral;Nunes, Ricardo Vianna;Broch, Jomara;Nilton, Rohloff Junior;Kohler, Tania Luiza;Cirilo, Edinan Hagdon
Animal Bioscience
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v.35
no.1
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pp.54-63
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2022
Objective: This study aimed to evaluate the replacement of degummed soybean oil (DSO) by acid soybean oil (ASO) in diets with or without the inclusion of emulsifier on broiler performance, relative organ weight, lipase activity, intestinal morphometry, and nutrient digestibility. Methods: A total of 704 1-day-old male broiler chicks were allotted to a 2×2 completely randomized factorial design (with or without emulsifier × two lipid sources [ASO and DSO]), with eight replicates and 22 birds each. The metabolizable energy level in diets with emulsifier was reduced by 40 kcal/kg from 1 to 21 d and 50 kcal/kg from 22 to 49 d. Results: Broilers fed diets containing ASO without emulsifier had higher (p = 0.005) weight gain than DSO-fed animals and with the inclusion of emulsifier had worse (p = 0.018) feed conversion ratio (FCR). Birds fed diets with emulsifier worsened FCR regardless of lipid source from 1 to 21 days (p = 0.006) and from 1 to 49 days (p = 0.0002). There was an increase (p = 0.026) in the relative pancreas weight, at 14 days, in birds fed diets containing ASO. Lipase activity and morphometry of the duodenum and jejunum, at 14 and 21 days, were not affected (p>0.05). The dietary inclusion of emulsifier improved the digestible energy (p = 0.053) in the presence of ASO. For the digestibility coefficients (gross energy, crude protein, and mineral matter), no interference was observed (p>0.05). Conclusion: The inclusion of emulsifier to energy-restricted diet with ASO maintained broiler performance in the first week, but worsened FCR in subsequent phases. The ASO can be considered as an alternative lipid source to DSO and does not interfere with the morphophysiological characteristics and performance of broilers. The combination of ASO and emulsifier increased the digestible energy content by 6.2%.
Jo, Chang Suk;Kim, So Young;Choi, Moon-Yeol;Kim, Mi Hyung;Kim, Mi Ryeo;Seo, Bu-il
The Korea Journal of Herbology
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v.37
no.1
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pp.1-9
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2022
Objective : This study was designed to investigate anti-diabetic effects of fermented soy bean extract with herbal medicines (Godjang) in diabetic rat models induced by streptozotocin (STZ) injection. Method : Changes in body weight, drinking water, and food intake were observed for 4 weeks before and after induction of diabetes mellitus in rats. The anti-diabetic capacity of Godjang was analyzed by fasting blood glucose (FBG) every week. Also, after 4 weeks of administration, the oral glucose tolerance test (OGTT) was performed, and then blood levels of insulin were checked. And serum levels of total cholesterol and triglycerides were determined. Histomorphological changes of liver, kidney and pancreatic tissues were also observed in STZ-induced diabetic rats and Godjang administered rats. Result : In Godjang administered group, body weight and water intake were more lower than that of STZ-induced diabetic rats. FBG was decreased in the Godjang administered group than STZ-induced diabetic group. According to OGTT, blood glucose levels at 30 minutes and 60 minutes significantly decreased in Godjang administered group than in STZ-induced diabetic control group. Administration of Godjang extract for 4W significantly decreased levels of serum glucose, total cholesterol (TC), triglycerides (TG) in diabetic rats. In histomorphological analysis of kidney, liver, Godjang administrated groups showed the inhibition of pathological damage. Conclusion : These results suggest that Godjang extract has an anti-diabetic action through decrease in serum glucose, TC, TG levels and recovery of the morphological changes in kidney and liver in STZ-induced diabetic rats.
Youjin, Hong;Sangjun, Lee;Sungji, Moon;Soseul, Sung;Woojin, Lim;Kyungsik, Kim;Seokyung, An;Jeoungbin, Choi;Kwang-Pil, Ko;Inah, Kim;Jung Eun, Lee;Sue K., Park
Journal of Preventive Medicine and Public Health
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v.55
no.6
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pp.529-538
/
2022
Objectives: This study aimed to identify the current patterns of cancer incidence and estimate the projected cancer incidence and mortality between 2020 and 2035 in Korea. Methods: Data on cancer incidence cases were extracted from the Korean Statistical Information Service from 2000 to 2017, and data on cancer-related deaths were extracted from the National Cancer Center from 2000 to 2018. Cancer cases and deaths were classified according to the International Classification of Diseases, 10th edition. For the current patterns of cancer incidence, age-standardized incidence rates (ASIRs) and age-standardized mortality rates were investigated using the 2000 mid-year estimated population aged over 20 years and older. A joinpoint regression model was used to determine the 2020 to 2035 trends in cancer. Results: Overall, cancer cases were predicted to increase from 265 299 in 2020 to 474 085 in 2035 (growth rate: 1.8%). The greatest increase in the ASIR was projected for prostate cancer among male (7.84 vs. 189.53 per 100 000 people) and breast cancer among female (34.17 vs. 238.45 per 100 000 people) from 2000 to 2035. Overall cancer deaths were projected to increase from 81 717 in 2020 to 95 845 in 2035 (average annual growth rate: 1.2%). Although most cancer mortality rates were projected to decrease, those of breast, pancreatic, and ovarian cancer among female were projected to increase until 2035. Conclusions: These up-to-date projections of cancer incidence and mortality in the Korean population may be a significant resource for implementing cancer-related regulations or developing cancer treatments.
Lee, Yun Jung;Lee, Yun Jae;Yoon, Jung Joo;Lee, So Min;Kim, Hye Yoom;Shin, Sun Ho;Kang, Dae Gill;Lee, Ho Sub
The Korea Journal of Herbology
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v.27
no.6
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pp.107-114
/
2012
Objectives : In this study, we investigated the anti-diabetic and anti-inflammatory effects of water extract from leaves of Ligustrum japonicum (WLJ) in db/db mouse. Methods : The db/db mice were treated orally with WLJ (300 mg/kg/day) for 10 weeks to examine the long-term effects on hyperglycemia and glomerular tissue as well as biochemical and functional abnormalities in the kidney. Results : WLJ treatment markedly reduced plasma levels of glucose, triglyceride, creatinine, and systolic blood pressure in diabetic db/db mouse. Treatment of WLJ significantly increased plasma level of high density lipoprotein (HDL)-cholesterol. We also found that overexpressions of vascular cellular adhesion molecule (VCAM)-1 and endothelin (ET)-1 were observed in aortic tissue of db/db mouse, whereas, WLJ suppressed both expression of VCAM-1 and ET-1 in aorta. In renal tissue, overexpressions of ICAM-1 and TGF-${\beta}1$ were found in untreated db/db mouse, however, significantly decreased those levels by WLJ treatment. The insulin immunoreactivity of the pancreatic islets remarkably increased in WLJ treated db/db mouse compared with untreated db/db mouse. Taken together, WLJ treatment ameliorated hyperglycemia and hyperlipidemia via improvement of insulin secretion and lipid metabolism, respectively. Furthermore, WLJ treatment also ameliorated hypertension via inhibition of inflammatory process in vascular and renal tissues. Conclusions : Ligustrum japonicum has an anti-diabetic and anti-inflammatory effects in db/db mouse. Thus, these results suggested a beneficial effect of Ligustrum japonicum in treatment with diabetes and diabetic vasculopathy.
Objective : Portulaca oleracea (PO) has been used as an important traditional medicine for inflammatory and bacterial diseases in East Asia. However, the protective effects of PO on acute pancreatitis (AP) is not well-known. Therefore, this study was performed to identify the anti-inflammatory and prophylactic effects of PO on cerulein-induced AP. Methods : AP was induced in mice via intraperitoneal injection of supramaximal concentrations of the stable cholecystokinin analogue cerulein ($50{\mu}g/kg$) given every hour for 6 times. Water extracts of PO (100, 300, or 500 mg/kg) was administrated intra-peritoneally 1 h prior to the first injection of cerulein. The mice were killed at 6 h after the final cerulein injection. Pancreas and lung were rapidly removed for morphologic and histochemical examination, myeloperoxidase (MPO) assay. Blood samples were taken to determine serum amylase and lipase activities. Results : Administration of PO significantly inhibited pancreatic weight/body weight ratio, pancreas and lung histological injury. And MPO activity which indicates neutrophil infiltration was inhibited by PO extracts on cerulein-induced pancreatitis. In addition, PO administration inhibited digestive enzymes such as serum amylase and lipase activity on cerulein-induced pancreatitis. Conclusion : Our results could suggest that pre-treatment of PO reduces the severity of cerulein-induced AP, thereby, PO could be used as a protective agent against AP. Also, this study could give a clinical basis that PO could be a drug or agent to prevent AP.
This study aimed to verify the antidiabetic effects of the unripe black raspberry extract (UBRE) in obese diabetic mice. For the experiment, animal model mice were divided into six groups: normal control, diabetic control, three experimental groups (treated with 75, 150, and 300 mg/kg single dose of UBRE), and a positive control (200 mg/kg metformin). The groups treated with 300 mg/kg UBRE and metformin had significantly reduced blood glucose and triglyceride levels in the diabetic mice compared to those in the vehicle control group. In addition, histopathological evaluation showed that UBRE increased the Langerhans area, cell number, and insulin concentration in the pancreatic islets of db/db mice. Therefore, UBRE exerts significant antidiabetic effects by decreasing the blood glucose and lipid levels, suggesting that it can be consumed as a functional diet for diabetic patients.
Immune and metabolic systems are important factors in maintaining homeostasis. Immune response and metabolic regulation are highly associated, so, when the normal metabolism is disturbed, the immune response changed followed the metabolic diseases occur. Likewise, obesity is highly related to immune response. Obesity, which is caused by an imbalance in energy metabolism, is associated with metabolic diseases, such as insulin resistance, type 2 diabetes, fatty liver diseases, atherosclerosis and hypertension. As known, obesity is characterized in chronic low-grade inflammation. In obesity, the microenvironment of immune cells became inflammatory by the unique activation phenotypes of immune cells such as macrophage, natural killer cell, T cell. Also, the immune cells interact each other in cellular or cytokine mechanisms, which intensify the obesity-induced inflammatory response. This phenomenon suggests the possibility of regulating the activation of immune cells as a pharmacological therapeutic strategy for obesity in addition to the common pharmacological treatment of obesity which is aimed at inhibiting enzymes such as pancreatic lipase and α-amylase or inhibiting differentiation of preadipocytes. In this review, we summarize the activation phenotypes of macrophage, natural killer cell and T cell, and their aspects in obesity. We also summarize the pharmacological substances that alleviates obesity by regulating the activation of immune cells.
Yoon Yong Choi;Hyeon Soo Lee;Su Yeon Baik;Sumin Lim;Hyo Won Jung;Seok Yong Kang;Yong-Ki Park
Journal of Korean Medicine for Obesity Research
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v.22
no.2
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pp.102-114
/
2022
Objectives: We investigated the effects of Allii Fistulosi Bulbus (AFB) on high fat diet (HFD)-induced obesity in mice and the regulation of energy metabolism in muscle tissues of mice. Methods: The C57BL/6 mice (6 weeks, male) were fed a HFD for 8 weeks and then administrated with AFB extract at 500 mg/kg (p.o.) once daily for 4 weeks. The body weight (BW), muscle weight, calorie intake, fasting blood glucose (FBG) and serum glucose, insulin, and low-density lipoprotein-cholesterol (LDL-C) levels were measured in mice. It was also observed the histological changes of pancreas, liver, and fat tissues with hematoxylin and eosin staining. It was investigated the phosphorylation of insulin receptor substrate 1 (IRS-1), Ser/Thr kinase (AKT), and adenosine monophosphate-activated protein kinase (AMPK), and the expression of phosphoinositide 3-kinase, glucose transporter type 4 (GLUT4), and sirtuin1 (Sirt1) in gastrocnemius tissues by western blot, respectively. Results: The increases of BWs, calorie intakes and FBG levels in obesity mice were decreased significantly by the administration of AFB extract. The AFB extract administration was reduced significantly serum levels of glucose, insulin, and LDL-C in obesity mice. The AFB extract inhibited lipid accumulation in liver tissues, hyperplasia of pancreatic islets, and enlargement of fat tissues in obesity mice. The phosphorylation of IRS-1 and AKT was increased significantly in muscle tissues and AMPK phosphorylation and the GLUT4 and Sirt1 expression were decreased significantly in muscle tissues after the AFB administration. Conclusions: Our study indicates that AFB extract improves symptoms of obesity through regulation of energy regulating proteins in muscle tissues.
Hyesook Lee;Jung-Hwa Han;Kangbin An;Yun Jeong Kang;Hyun Hwangbo;Ji Hye Heo;Byung Hyun Choi;Jae-Joon Kim;Seo Rin Kim;Soo Yong Lee;Jin Hur
BMB Reports
/
v.56
no.6
/
pp.359-364
/
2023
KAI1/CD82, a membrane tetraspanin protein, can prevent various cancers and retinal disorders through its anti-angiogenic and anti-metastatic capacity. However, little is known about its anti-inflammatory effect and molecular mechanism. Therefore, the present study aimed to inLPSvestigate effect of a recombinant protein of the large extracellular domain of human KAI1 (Gly 111-Leu 228, rhKAI1) on lipopolysaccharides (LPS)-stimulated RAW264.7 macrophage-like cells and mouse bone marrow-derived macrophages (BMDM) and to identify its underlying mechanism. Our data showed that rhKAI1 suppressed expression levels of classically macrophages (M1) phenotype-related surface markers F4/80+CD86+ in LPS-stimulated BMDM and RAW264.7 cells. In addition, LPS markedly increased mRNA expression and release levels of pro-inflammatory cytokines and mediators such as interleukin (IL)-1β, IL-6, tumor necrosis factor-α, cyclooxygenase-2, nitric oxide and prostaglandin E2, whereas these increases were substantially down-regulated by rhKAI1. Furthermore, LPS strongly increased expression of NF-κB p65 in the nuclei and phosphorylation of ERK, JNK, and p38 MAPK. However, nuclear translocation of NF-κB p65 and phosphorylation of JNK were greatly reversed in the presence of rhKAI1. Especially, rhKAI1 markedly suppressed expression of toll-like receptor (TLR4) and prevented binding of LPS with TLR4 through molecular docking predict analysis. Importantly, Glu 214 of rhKAI1 residue strongly interacted with Lys 360 of TLR4 residue, with a binding distance of 2.9 Å. Taken together, these findings suggest that rhKAI1 has an anti-inflammatory effect on LPS-polarized macrophages by interacting with TLR4 and down-regulating the JNK/NF-κB signaling pathway.
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