• Journal of Animal Science and Technology
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• v.66 no.1
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• pp.79-92
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• 2024

Global warming is a key challenge subjecting animals to heat stress conditions resulting in multiple physiological alterations in tropical climate. Dietary approach seems to be the more friendly approach to curb the adverse effects of heat stress in rabbits. Some herbs have been categorized to have high potential for promotion of immune responses for amelioration of heat stress. Thus, this research aims to evaluate the potential of Mistletoe (Viscum album), Moringa (Moringa oleifera) and Phyllanthus (Phyllanthus amarus) leaf meal as herbal supplements for the alleviation of heat stress in female rabbits by measuring improvement in sex and stress hormonal responses in serum biochemistry. 80 Rabbit does were exposed to 4 dietary groups supplemented with each of Mistletoe, Moringa, Phyllanthus and a control in an 84-day trial at the summit of thermal stress in South west Nigeria. Growth indices were monitored throughout the study, blood samples were compiled at the end of the trial to assess serum biochemistry, stress and sex hormonal responses of the Does using standard protocols. The results revealed that final weight and weight gain of Does fed on Phyllanthus were significantly (p < 0.05) higher (11.46% and 14.25%, respectively) than Does on control. The herbal supplements enhance glucose, protein, albumin and globulin, reduced cholesterol, and creatinine of Does under heat stress conditions. Among the herbal treatment groups, mistletoe, moringa and phyllanthus had 12.42%, 18.39% and 16.90%, respectively, lower corticosterone than control groups which had 39.76ng/ml. Triiodothyronine of Does fed control were significantly (p < 0.05) lower than Does on Moringa oleifera and Phyllanthus amarus supplements. Estradiol and Follicle stimulating hormone of rabbit Does fed on moringa supplement were significantly (p < 0.05) higher than other treatments. In conclusion, the herbal supplements tend to mitigate the detrimental outcome of thermal stress on Does by suppressing stress hormones. Moringa oleifera and Phyllanthus amarus enhanced sex hormones while Phyllanthus amarus confered growth promoting effects on the Does.

• Korean Journal of Radiology
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• v.22 no.6
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• pp.994-1004
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• 2021

Objective: To extract pulmonary and cardiovascular metrics from chest CTs of patients with coronavirus disease 2019 (COVID-19) using a fully automated deep learning-based approach and assess their potential to predict patient management. Materials and Methods: All initial chest CTs of patients who tested positive for severe acute respiratory syndrome coronavirus 2 at our emergency department between March 25 and April 25, 2020, were identified (n = 120). Three patient management groups were defined: group 1 (outpatient), group 2 (general ward), and group 3 (intensive care unit [ICU]). Multiple pulmonary and cardiovascular metrics were extracted from the chest CT images using deep learning. Additionally, six laboratory findings indicating inflammation and cellular damage were considered. Differences in CT metrics, laboratory findings, and demographics between the patient management groups were assessed. The potential of these parameters to predict patients' needs for intensive care (yes/no) was analyzed using logistic regression and receiver operating characteristic curves. Internal and external validity were assessed using 109 independent chest CT scans. Results: While demographic parameters alone (sex and age) were not sufficient to predict ICU management status, both CT metrics alone (including both pulmonary and cardiovascular metrics; area under the curve [AUC] = 0.88; 95% confidence interval [CI] = 0.79-0.97) and laboratory findings alone (C-reactive protein, lactate dehydrogenase, white blood cell count, and albumin; AUC = 0.86; 95% CI = 0.77-0.94) were good classifiers. Excellent performance was achieved by a combination of demographic parameters, CT metrics, and laboratory findings (AUC = 0.91; 95% CI = 0.85-0.98). Application of a model that combined both pulmonary CT metrics and demographic parameters on a dataset from another hospital indicated its external validity (AUC = 0.77; 95% CI = 0.66-0.88). Conclusion: Chest CT of patients with COVID-19 contains valuable information that can be accessed using automated image analysis. These metrics are useful for the prediction of patient management.

• Journal of Life Science
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• v.34 no.6
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• pp.399-407
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• 2024

Angiogenesis is the process by which new blood vessels form from existing blood vessels. This phenomenon occurs during growth, healing, and menstrual cycle changes. Angiogenesis is a complex and multifaceted process that is important for the continued growth of primary tumors, metastasis promotion, the support of metastatic tumors, and cancer progression. Impaired angiogenesis can lead to cancer, autoimmune diseases, rheumatoid arthritis, cardiovascular disease, and delayed wound healing. Currently, there are only a handful of effective antiangiogenic drugs. Recent studies have shown that natural marine products exhibit antiangiogenic effects. In a previous study, we reported that the hexane extract of H. fusiformis (HFH) could inhibit the development of new blood vessels both in vitro and in vivo. The aim of this study was to describe the inhibitory effect of chloroform extracts of H. fusiformis on angiogenesis. To investigate how chloroform extract prevents blood vessel growth, we examined its effects on HUVEC, including cell migration, invasion, and tube formation. In a mouse Matrigel plug assay, H. fusiformis chloroform extract (HFC) also inhibited angiogenesis in vivo. Certain proteins associated with blood vessel growth were reduced after HFC treatment. These proteins include vascular endothelial growth factor (VEGF), mitogen-activated protein kinase (MAPK)/extracellular signal transduction kinase, and serine/threonine kinase 1 (AKT). These studies have shown that the chloroform extract of H. fusiformis can inhibit blood vessel growth both in vitro and in vivo.

• IMMUNE NETWORK
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• v.21 no.6
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• pp.43.1-43.14
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• 2021

Group 3 innate lymphoid cells (ILC3), which express IL-22 and IL-17A, has been introduced as one of pathologic cells in axial spondyloarthritis (axSpA). Dyslipidaemia should be managed in axSpA patients to reduce cardiovascular disease, and dyslipidaemia promotes inflammation. This study aimed to reveal the role of circulating ILC3 in axSpA and the impact of dyslipidaemia on axSpA pathogenesis. AxSpA patients with or without dyslipidaemia and healthy control were recruited. Peripheral blood samples were collected, and flow cytometry analysis of circulating ILC3 and CD4⁺ T cells was performed. The correlation between Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-reactive protein (CRP) and circulating immune cells was evaluated. The effect of oxidized low-density lipoprotein cholesterol (oxLDL-C) on immune cell differentiation was confirmed. AxSpA human monocytes were cultured with with oxLDL-C, IL-22, or oxLDL-C plus IL-22 to evaluate osteoclastogenesis using tartrate-resistant acid phosphatase (TRAP) staining and real-time quantitative PCR of osteoclast-related gene expression. Total of 34 axSpA patients (13 with dyslipidaemia and 21 without) were included in the analysis. Circulating IL-22⁺ ILC3 and Th17 were significantly elevated in axSpA patients with dyslipidaemia (p=0.001 and p=0.034, respectively), and circulating IL-22⁺ ILC3 significantly correlated with ASDAS-CRP (Rho=0.4198 and p=0.0367). Stimulation with oxLDL-C significantly increased IL-22⁺ ILC3, NKp44^- ILC3, and Th17 cells, and these were reversed by CD36 blocking agent. IL-22 and oxLDL-C increased TRAP⁺ cells and osteoclast-related gene expression. This study suggested potential role of circulating IL-22⁺ ILC3 as biomarker in axSpA. Furthermore, dyslipidaemia augmented IL-22⁺ ILC3 differentiation, and oxLDL-C and IL-22 markedly increased osteoclastogenesis of axSpA.

• IMMUNE NETWORK
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• v.22 no.2
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• pp.18.1-18.15
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• 2022

Dysfunction of mitochondrial metabolism is implicated in cellular injury and cell death. While mitochondrial dysfunction is associated with lung injury by lung inflammation, the mechanism by which the impairment of mitochondrial ATP synthesis regulates necroptosis during acute lung injury (ALI) by lung inflammation is unclear. Here, we showed that the impairment of mitochondrial ATP synthesis induces receptor interacting serine/threonine kinase 3 (RIPK3)-dependent necroptosis during lung injury by lung inflammation. We found that the impairment of mitochondrial ATP synthesis by oligomycin, an inhibitor of ATP synthase, resulted in increased lung injury and RIPK3 levels in lung tissues during lung inflammation by LPS in mice. The elevated RIPK3 and RIPK3 phosphorylation levels by oligomycin resulted in high mixed lineage kinase domain-like (MLKL) phosphorylation, the terminal molecule in necroptotic cell death pathway, in lung epithelial cells during lung inflammation. Moreover, the levels of protein in bronchoalveolar lavage fluid (BALF) were increased by the activation of necroptosis via oligomycin during lung inflammation. Furthermore, the levels of ATP5A, a catalytic subunit of the mitochondrial ATP synthase complex for ATP synthesis, were reduced in lung epithelial cells of lung tissues from patients with acute respiratory distress syndrome (ARDS), the most severe form of ALI. The levels of RIPK3, RIPK3 phosphorylation and MLKL phosphorylation were elevated in lung epithelial cells in patients with ARDS. Our results suggest that the impairment of mitochondrial ATP synthesis induces RIPK3-dependent necroptosis in lung epithelial cells during lung injury by lung inflammation.

• IMMUNE NETWORK
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• v.22 no.4
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• pp.35.1-35.16
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• 2022

Tobacco smoking (TS) has been known as one of the most potent risk factors for airway inflammatory diseases. However, there has been a paucity of information regarding the immunologic alteration mediated by TS in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). To identify the effect of TS, we harvested human tissue samples (never smoker: n=41, current smoker: n=22, quitter: n=23) and analyzed the expression of epithelial-derived cytokines (EDCs) such as IL-25, IL-33, and thymic stromal lymphopoietin. The expressions of Th2 cytokines and total serum IgE showed a type-2 inflammatory alteration by TS. In addition, the epithelial marker E-cadherin and epithelial-mesenchymal transition (EMT)-associated markers (N-cadherin, α-SMA, and vimentin) were evaluated. Histological analysis showed that EDC expressions were upregulated in the current smoker group and downregulated in the quitter group. These expression patterns were consistent with mRNA and protein expression levels. We also found that the local Th2 cytokine expression and IgE class switching, as well as serum IgE levels, were elevated in the current smoker group and showed normal levels in the quitter group. Furthermore, the expressions of E-cadherin decreased while those of N-cadherin, α-SMA, and vimentin increased in the current smoker group compared those in the never smoker group. Taken together, these results indicate that TS contributes to the deterioration of pathogenesis by releasing local EDCs and Th2 cytokines, resulting in EMT in patients with CRSwNP. We verified that alterations of immunological response by TS in sinonasal epithelium can play a vital role in leading to CRSwNP.

• Animal Bioscience
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• v.37 no.7
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• pp.1225-1235
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• 2024

Objective: The objective of the study was to determine the effects of feeding fermented cassava leaf meal (FCLM) on growth performance, carcass characteristics and meat sensory evaluation of broiler chickens. Methods: A total of 160 Cobb-500 chickens were used during the phases of growing (21 days of age; initial weight 0.39±0.025 kg/bird) and finishing (35 days of age; initial weight 1.023±0.164 kg/bird). The whole experiment lasted for four weeks. The FCLM was included in starter and finishing diets at 0, 50, 100, and 150 g/kg inclusion levels. Total feed intake (TFI), weight gain (WG), feed conversion ratio, and nutrient digestibility were recorded. Sensory evaluation of breast meat was used to determine the eating quality of the meat prepared using roasting and boiling methods. Results: The TFI and WG decreased (p<0.05) with increasing inclusion levels of FCLM in the diets of growing chickens. Crude protein digestibility for chickens fed 0 and 50 g/kg FCLM was higher (p<0.05) than for chickens subjected to a diet with 150 g/kg FCLM. During the finishing phase, TFI increased linearly (p<0.05) with increasing inclusion level of FCLM in chicken diets, while WG decreased (p<0.05) with inclusion level of FCLM. Treatment diets had no effect (p>0.05) on the eating qualities of breast meat. However, juiciness was significant (p<0.05) for the cooking method and treatment interaction. At 50 g/kg inclusion level, boiled meat had a higher (p<0.05) juiciness score than roasted meat. Tenderness, on the other hand, was significant (p<0.05) for the interaction of gender and treatment. Females considered the boiled meat to be more tender than the males at 150 g/kg inclusion level. Using principal component analysis, a positive correlation was observed between teeth adhesion and fibrousness, flavour and juiciness, and springiness and tenderness. Conclusion: From the study, it can be concluded that FCLM can be used as an ingredient in the diets of broiler chickens. Inclusion level of 50 g/kg can be used in chicken diets during the growing phase, whereas in the finishing phase, inclusion level of 150 g/kg FCLM can be used. The FCLM did not affect the eating quality of breast meat.

• Clinical Nutrition Research
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• v.12 no.3
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• pp.199-217
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• 2023

People with higher genetic predisposition to obesity are more susceptible to cardiovascular diseases (CVDs) and healthy plant-based foods may be associated with reduced risks of obesity and other metabolic markers. We investigated whether healthy plant-foods-rich dietary patterns might have inverse associations with cardiometabolic risk factors in participants at genetically elevated risk of obesity. For this cross-sectional study, 377 obese and overweight women were chosen from health centers in Tehran, Iran. We calculated a healthy plant-based diet index (h-PDI) in which healthy plant foods received positive scores, and unhealthy plant and animal foods received reversed scores. A genetic risk score (GRS) was developed based on 3 polymorphisms. The interaction between GRS and h-PDI on cardiometabolic traits was analyzed using a generalized linear model (GLM). We found significant interactions between GRS and h-PDI on body mass index (BMI) (p = 0.02), body fat mass (p = 0.04), and waist circumference (p = 0.056). There were significant gene-diet interactions for healthful plant-derived diets and BMI-GRS on high-sensitivity C-reactive protein (p = 0.03), aspartate aminotransferase (p = 0.04), alanine transaminase (p = 0.05), insulin (p = 0.04), and plasminogen activator inhibitor 1 (p = 0.002). Adherence to h-PDI was more strongly related to decreased levels of the aforementioned markers among participants in the second or top tertile of GRS than those with low GRS. These results highlight that following a plant-based dietary pattern considering genetics appears to be a protective factor against the risks of cardiometabolic abnormalities.

• Journal of Yeungnam Medical Science
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• v.14 no.1
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• pp.53-66
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• 1997

Insulin resistance is a prominent feature of diabetic state and has heterogeneous nature. However, the pathogenetic sequence of events leading to the emergence of the defect in insulin action remains controversial. It is well-known that prolonged hyperglycemia and hyperinsulinemia are one of the causes of development of insulin resistance, but both hyperglycemia and hyperinsulinemia stimulate glucose uptake in peripheral tissue. Therefore, it is hypothesized that insulin resistance may be generated by a kind of protective mechanism preventing cellular hypertrophy. In this study, to evaluate whether the acutely increased glucose uptake inhibits further glucose transport stimulated by insulin, insulin sensitivity was measured after preloaded glucose infusion for 2 hours at various conditions in rats. And also, to evaluate the mechanism of decreased insulin sensitivity, insulin receptor binding affinity and glucose transporter 4 (GLUT4) protein of plasma membrane of gastrocnemius muscle were assayed after hyperinsulinemic euglycemic clamp studies. Experimental animals were divided into five groups according to conditions of preloaded glucose infusion: group I, basal insulin ($14{\pm}1.9{\mu}U/ml$) and basal glucose ($75{\pm}0.7mg/dl$), by normal saline infusion; group II, normal insulin ($33{\pm}3.8{\mu}U/ml$) and hyperglycemia ($207{\pm}6.3mg/dl$), by somatostatin and glucose infusion; group III, hyperinsulinemia ($134{\pm}34.8{\mu}U/ml$) and hyperglycemia ($204{\pm}4.6mg/dl$), by glucose infusion; group IV, supramaximal insulin ($5006{\pm}396.1{\mu}U/ml$) and euglycemia ($l00{\pm}2.2mg/dl$), by insulin and glucose infusion; group V, supramaximal insulin ($4813{\pm}687.9{\mu}U/ml$) and hyperglycemia ($233{\pm}3.1mg/dl$), by insulin and glucose infusion. Insulin sensitivity was assessed with hyperinsulinemic euglycemic clamp technique. The amounts of preloaded glucose infusion(gm/kg) were $1.88{\pm}0.151$ in group II, $2.69{\pm}0.239$ in group III, $3.54{\pm}0.198$ in group IV, and $4.32{\pm}0.621$ in group V. Disappearance rates of glucose (Rd, mg/kg/min) at steady state of hyperinsulinemic euglycemic clamp studies were $16.9{\pm}3.88$ in group I, $13.5{\pm}1.05$ in group II, $11.2{\pm}1.17$ in group III, $13.2{\pm}2.05$ in group IV, and $10.4{\pm}1.01$ in group V. A negative correlation was observed between amount of preloaded glucose and Rd (r=-0.701, p<0.001) when all studies were combined. Insulin receptor binding affinity and content of GLUT4 were not significantly different in all experimental groups. These results suggest that increased glucose uptake may inhibit further glucose transport and lead to decreased insulin sensitivity.

• The Korean Journal of Nuclear Medicine
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• v.38 no.1
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• pp.85-98
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• 2004

Purpose: Cellular uptake of $^{99}mTc$-sestamibi (MIBI) and $^{99}mTc$-tetrofosmin (TF) is low in cancer cells expressing multidrug resistance(MDR) by p-glycoprotein(Pgp) or multidrug related protein(MRP). Verapamil is known to increase cellular uptake of MIBI in MDR cancer cells, but is recently reported to have different effects on tracer uptake in certain cancer cells. This study was prepared to evaluate effects of verapamil on cellular uptake of MIBI and TF in several cancer cells. Materials and Methods: Celluar uptakes of Tc-99m MIBI and TF were measured in erythroleukermia K562 cell, breast cancer MCF7 cell, and human ovarian cancer SK-OV-3 cells, and data were compared with those of doxorubicin-resistant K562(Ad) cells. RT-PCR and Western blot analysis were used for the detection of mdr1 mRNA and Pgp expression, and to observe changes in isotypes of PKC enzyme. Effects of verapamil on MIBI and TF uptake were evaluated at different concentrations upto $200{\mu}M\;at\;1{\times}10^6\;cells/ml\;at\;37^{\circ}C$. Radioactivity in supernatant and pellet was measured with gamma counter to calculate cellular uptake ratio. Toxicity of verapamil was measured with MTT assay. Results: Cellular uptakes of MIBI and TF were increased by time in four cancer cells studied. Co-incubation with verapamil resulted in an increase in uptake of MIBI and TF in K562(Adr) cell at a concentration of $100{\mu}M$ and the maximal increase at $50{\mu}M$ was 10-times to baseline. In contrast, uptakes of MIBI and TF in K562, MCF7, SK-OV3 cells were decreased with verapamil treatment at a concentration over $1{\mu}M$. With a concentration of $200{\mu}M$ verapamil, MIBI and TF uptakes un K562 cells were decreased to 1.5 % and 2.7% of those without verapamil, respectively. Cellular uptakes of MIBI and TF in MCF7 and SK-OV-3 cells were not changed with $10{\mu}M$, but were also decreased with verapamil higher than $10{\mu}M$, resulting 40% and 5% of baseline at $50{\mu}M$. MTT assay of four cells revealed that K562, MCF7, SK-OV3 were not damaged with verapamil at $200{\mu}M$. Conclusion: Although verapamil increases uptake of MIBI and TF in MDR cancer cells, cellular uptakes were further decreased with verapamil in certain cancer cells, which is not related to cytotoxicity of drug. These results suggest that cellular uptakes of both tracers might differ among different cells, and interpretation of changes in tracer uptake with verapamil in vitro should be different when different cell lines are used.