Gynostemma pentaphyllum promotes strained skeletal muscle protein regeneration by adjustment of liver and spleen function via PXR-IL-6-SERCA1a

Objectives : The purpose of this research is to understand melanin with both Korean and Western medicine.Methods : We investigated the comprehension of melanin in both western and Korean medicine through literature review and studied relationships between melanin and five viscera(五臟), especially liver(肝), spleen(脾), kidney(腎). We Also studied representative pigmentary disorders(melasma, vitiligo) in western and Korean medicine to figure out how to understand pigmentary disorders in oriental medicine.Results : The results are as follows. 1. Melanin is associate with liver, because free coursing(疎泄) function of liver is the origin of transport melanin to keratinocyte from melanocyte. Also, melanogenesis factors like MITF and CREB are closely associated with liver and pigmentary disorders occur frequently after stress conditions or women. 2. Melanin is absorbed and scattered in keratinocytes by the function of spleen. Pigmentary disorders result from failure of spleen and formation of phlegm-retained fluid(痰飮). 3. Kidney essence(腎精) is the origin of melanin formation. In addition, corticosteroid, the major hormone of melanogenesis is secreted by adrenalin and adrenalin belongs to kidney(腎) in Korean medicine. 4. Melasma is created by disorder of melanin transport and absorbtion, so melasma is associated liver (肝) and spleen(脾). Therefore the treatment for melasma may focus on improvement function of liver and spleen. 5. The destruction of melanocyte or abnormal melanogenesis by disorder of the immune system, metabolic and affective disorders can make vitiligo, so vitiligo is associated with liver and kidney which are major part of melanin formation. Therefore the treatment of vitiligo can focus on improvement function of liver(肝) and kidney(腎).Conclusion : We compared Korean and western medicine to understand melanin. We also interpreted the mechanism of melanin and pigmantary disorders in western medicine and considered the relationship with visceral manifestation theory(臟象論) in traditional Korean medicine. Further studies are needed to apply comprehension of melanin to clinical stage.

The liver is essential for nutritional balance in fish, and liver damage in farmed fish often arises from factors like overfeeding, causing various health issues. Clinical observations indicate that liver diseases frequently involve spleen dysfunction, and there is evidence to suggest that the spleen has a significant impact on liver function. However, there has been no discussion on the role of the spleen in maintaining liver health in fish. To understand the role of fish spleen in liver metabolism, this study selected Nile tilapia (Oreochromis niloticus) as the experimental material and first established a tilapia splenectomy model. Various biochemical parameters of the liver and serum were measured, and the liver metabolism characteristics of the splenectomy group (SP group) and the sham operation group (SO group) were analyzed using metabolomics. After splenectomy, biochemical parameters of the liver and serum showed abnormalities, including significant increases in total cholesterol (T-CHO) and serum total bile acid (TBA) levels, alongside a significant decrease in liver TBA levels, suggesting impaired metabolic function and cholesterol deposition in the liver. Metabolomics analysis showed that metabolites such as lipids, lipid-like molecules, and organic acids and derivatives were differentially regulated between the SO and SP group. KEGG analysis showed that differential metabolites were enriched in lipid metabolism and amino acid metabolism. The metabolic pathway analysis of differential metabolites showed that after splenectomy, the low-activity urea cycle in the liver may accelerate lipid synthesis, while low concentrations of aromatic amino acids and taurine may inhibit lipid catabolism. These results indicate that after splenectomy, the liver metabolic capacity is impaired, which causes abnormal lipid metabolism by interfering with amino acid metabolism, making splenectomy tilapia liver at risk of liver disease, including cholesterol deposition, hepatic steatosis and nonalcoholic fatty liver disease (NAFLD). Our results show that the spleen is involved in regulating liver lipid and amino acid metabolism, and the spleen may interfere with lipid metabolism by regulating liver amino acid metabolism. Our data can provide support for further research on liver and spleen functions and the immune-nutrient metabolism mechanisms in fish, as well as new ideas for healthy fish farming.

This article aims to illustrate the function of the Spleen in Traditional Chinese Medicine (TCM) in the context of modern medicine. TCM has been practiced since ancient times in China for the prevention and/or treatment of diseases. Yet, the complete understanding of its theoretical basis in relation to clinical practice from the modern medicine perspective is still lacking. According to TCM theory, the Spleen, as one of the five Zang (i.e., visceral organs), plays an important role in various physiological functions, including digestion and absorption of nutrients, regulation of water retention and excretion, facilitation of blood perfusion to skeletal muscle and on the optimal functioning of the immune system. Clinical applications of herbal formulations for the treatment of Spleen dysfunction (i.e., Spleen deficiency—a decline in Spleen function) and their pharmacological activities are described. The view point of TCM on how emotions (or Qing Zhi) can influence the body function is introduced. The relationship between anxiety and Spleen function has been analyzed by reviewing relevant research studies in modern medicine. These findings suggest that the cause/consequence relationship between anxiety and Spleen function may be bi-directional.

Objective To investigate the influence of diameter of liver outflow vein on portal hypertension and artificial blood vessel (ABV) patency rate in Budd-Chiari syndrome (BCS) patients undergoing atrial caval shunting (ACS).Methods We recruited 209 patients,who had undergone ACS for Ⅱ type of BCS.Those patients with unobstructed liver outflow vein were included into group A and the patients with stenosed liver outflow vein into group B.Free portal pressure (FPP) was measured before and after ABV opening.Portal vein velocity (Vpv),liver function,spleen volume and function,esophagogastric varices and ABV patency were evaluated postoperatively.Results After ABV opening,FPP decreased significantly in group A than group B (t =10.45,P ＜ 0.05).Vpv accelerated significantly in group A 2 weeks after operation than group B (t =12.81,P ＜ 0.05).Apparent improvement of liver function,spleen function and esophagogastric varices and reduction of spleen volume were observed in group A patients than group B patients (P ＜ 0.05).Reduction of esophagogastric varices in group A was better than in group B (x2 =44.73,P ＜ 0.05).By postoperative follow up,ABV patency of group A was higher than group B (P ＜ 0.05).Conclusions Patency status of liver outflow vein significantly influences postoperative portal vein pressure and closely correlats to ABV patency rate after ACS. Key words: Budd-Chiari syndrome; Blood vessel prosthesis ; Hypertension, portal; Esophageal and gastric varices

the progressive loss of muscle mass, commonly termed sarcopenia, accompanies the process of healthy aging ([27][1]). The underlying basis of this condition, in a very simplistic view, would be at a more advanced age skeletal muscle proteins are being lost because of an imbalance between muscle

In an herbal formulation, interaction or synergism between hundreds of constituents present in each of the plant is the foundation for most of herbal medicine systems including Ayurveda, traditional Chinese medicine (TCM), Kampo, Siddha, Arabic, and African herbal medicine. This chapter explains on few possible herbal combinations in alleviating diseases. Besides, food can also interact with drugs, as food encompasses minerals and vitamins, and phytochemical/polyphenol-rich vegetables, spices, and fruits. Food also generally follows the same route as drug in crossing the GI tract and undergoes biotransformation in the liver. Marked interaction between these food components and drug occurs with few being synergistic and others being adverse in nature.Keywords5′-Methoxyhydnocarpin (5′-MHC)Cmax (maximum concentration in the plasma)Drug Interaction Database (DIDB)Epigallocatechin-3-0-gallate (EGCG)Food-drug interactions (FDI)Gamma-aminobutyric acid (GABA)Herb-herb interactions (HHI)High-density lipoprotein (HDL)High-fat diet (HFD)Liver function (LF)Minimum inhibitory concentration (MIC)Norfloxacin A multidrug resistant (norA MDR)Nuclear factor erythroid 2-related factor 2 signaling pathway (Nrf2)Sodium channel 2 subunit (SCN)Spleen function (SF)tmax (time to reach maximum concertation in the plasma)Traditional Chinese medicine (TCM)Tricarboxylic acid (TCA)Uridine 5′-diphospho-glucuronosyltransferases (UGT)Xiaoyaosan (XS)P-glycoprotein (P-gp)Liquid chromatography-mass spectrometry (LC-MS)

Ado- Trastuzumab-Emtansine is approved by EMA and FDA for treatment of HER-2-positive metastatic breast cancer. The drug combines the cytotoxic activity of emtansine with trastuzumab [1,2,3]. Here we are describing 50- year old woman with 3-ple positive left breast cancer with metastasis to left axillary lymph nodes treated with the drug. The patient had normal liver and spleen structure on CT of the abdomen with I.V. contrast, along with a normal liver function test. However she did have a mild elevation of her indirect bilirubin after the initiation of the drug. Despite the normal liver and spleen and absence of Cirrhosis the patient developed drug induced spider angiomas on the upper chest, upper back, shoulders along with palmar erythema. The association of the Ado-Trastuzumab-Emtansine with spider angiomas and palmar erythema in those with normal liver and spleen function, with only a mild elevation of indirect bilirubin is discussed in the article [1].

With much interest, I read the recent paper by Lam et al. titled ‘‘Splenomegaly-associated thrombocytopenia after hepatic Yittriun-90 radioembolization’’ [1]. In their paper author’s report the increase in size of the spleen and correlating thrombocytopenia in patients who have had Yittrium-90 radioembolization. As explanation for this observation authors have offered increase in portal pressure as a potential mechanism, although they have questioned contribution of other partially unknown factors in this event [1]. Although, change in portal flow and hemodynamics to explain splenomegaly is convincing, perhaps what is referred to in the literature as ‘‘liver-spleen axis (LSA)’’ or ‘‘liver and spleen cross talk’’ could be among the unknown factors the manuscript is referring to [2, 3]. It should be noted that there are previous reports describing similar change in hepatic and splenic size following radioembolization [4, 5]. In fact, there is a growing body of evidence, based on animal studies that liver and spleen are closely related in physiology and morphological changes and both organ respond to common growth factors [6]. Further it has been shown that liver regeneration capacity is actively inhibited by spleen through secretion of cytokine such as transforming growth factor-b1 and hepatocyte growth factor activator inhibitor type 1 and 2 [7]. Transforming growth factor-b1 (TGF-b1) is reported to be the most potent cytokine responsible for liver fibrosis, and similarly interleukin-6 (IL-6) is emerging as an important factor in modulating hepatic regeneration [8, 9]. Increase in splenic TGF-b1 produced by macrophages and cytokines such as IL-6 could be responsible for progression of liver fibrosis and regeneration in patients with liver cirrhosis [3]. Presence of liver spleen interconnectivity is supported based on observations that have been made in patients with histologically proven non-alcoholic steatohepatitis (NASH). Patients with NASH have higher splenic longitudinal diameter (SLD), blood IL-6 levels, and vascular endothelial growth factor concentration (VEGF) compared to group of control patients with out NASH [10]. LSA may also explain changes occurring following spleen or liver resection. It has shown that splenectomy not only decreases portal pressure and be a cure for hypersplenism but also it could inhibit liver fibrosis, cause an increase in platelet count and provide some improvements in hepatic function [11–14]. Kim et al. have reported temporal evolution of liver and spleen size following donor hepatectomy resulting in 80 % increase in remnant liver size and 30 % increase in splenic size by 6 months accompanied by sustained hypersplenism [15]. All of these observations are supporting the presence and impact of LSA. In addition, there are less-known hemodynamic changes that occur in patients who have undergone splenectomy that may have clinical implication. Ozban et al. reported that exercise in splenectomized individuals not only results in decrease in splanchnic blood flow but also increases blood viscosity [16]. Further proof to complexity of splenic functions beyond its widely known hematological and immune functions is the role spleen plays in lipid metabolism and etiology of atherosclerosis [17, 18]. In summary, I would like to thank the authors for creating this opportunity to dwell on LSA and spleen functions. To this date, indications for splenic interventions have been largely limited to image-guided biopsy, M. Midia (&) Department of Radiology, Cogeco, 1200 Main Street West, Hamilton, ON, Canada e-mail: mmidia@cogeco.ca

Posthepatectomy liver failure (PHLF) is the most leading cause of mortality following hepatectomy in patients with hepatocellular carcinoma (HCC). Platelet count was reported to be a simple but useful indicator of liver cirrhosis and function of spleen. Spleen stiffness (SS) was used to evaluate the morphological change of spleen and was reported to be related to liver cirrhosis and portal hypertension. However, the predictive value of platelet to spleen stiffness ratio (PSR) on PHLF remains unknown. A retrospective study was performed to analyze 158 patients with HCC following hepatectomy from August 2015 to February 2016. Univariate and multivariate analyses were performed to evaluate the value of each risk factor for predicting PHLF. The predictive efficiency of the risk factors was evaluated by receiver operating characteristic (ROC) curve. PHLF occured in 23 (14.6%) patients. PSR (P<0.001, odds ratio (OR) = 0.622, 95% confidence interval (CI) 0.493~0.784), hepatic inflow occlusion (HIO) (P = 0.003, OR = 1.044, 95% CI 1.015~1.075) and major hepatectomy (P = 0.019, OR = 5.967, 95% CI 1.346~26.443) were demonstrated to be the independent predictive factors for development of PHLF in a multivariate analysis. Results of the present study suggested PSR is a novel and non-invasive model for predicting PHLF in patients with HCC.

Asplenia or functional hyposplenism are risk factors for severe infections, and vaccinations against encapsulated bacteria are advised. There are only limited data regarding the spleen function of cirrhotic patients. We evaluated spleen function in patients with liver cirrhosis, who were prospectively enrolled in this study. Spleen function was evaluated by the measurement of pitted erythrocytes. Functional hyposplenism was defined as a percentage of PE of >15%. 117 patients, mean age 58.4 years and 61.5% (n = 72) male with liver cirrhosis were included. Functional hyposplenism was diagnosed in 28/117 patients (23.9%). Pitted erythrocytes correlated with albumin (p = 0.024), bilirubin (p<0.001), international normalized ratio (INR; p = 0.004), model of end-stage liver disease (MELD) score (p<0.001) and liver stiffness (p = 0.011). Patients with functional hyposplenism had higher MELD scores (median 13 vs. 10; p = 0.021), liver stiffness (46.4 kPa vs. 26.3 kPa; p = 0.011), INR (1.3 vs. 1.2; p = 0.008) and a higher Child-Pugh stage (Child C in 32.1% vs. 11.2%; p = 0.019) as compared to patients without functional hyposplenism. Functional hyposplenism was not associated with the etiology of cirrhosis. Importantly, 9/19 patients with Child C cirrhosis had functional hyposplenism. A quarter of patients with liver cirrhosis and almost 50% of patients with Child C cirrhosis have functional hyposplenism. Functional hyposplenism is associated with poor liver function and the degree of portal hypertension, which is characterized by higher liver stiffness measurements in transient elastography.

BackgroundAsplenia or functional hyposplenism are risk factors for severe infections, and vaccinations against encapsulated bacteria are advised. There are only limited data regarding the spleen function of cirrhotic patients.MethodsWe evaluated spleen function in patients with liver cirrhosis, who were prospectively enrolled in this study. Spleen function was evaluated by the measurement of pitted erythrocytes. Functional hyposplenism was defined as a percentage of PE of >15%.Results117 patients, mean age 58.4 years and 61.5% (n = 72) male with liver cirrhosis were included. Functional hyposplenism was diagnosed in 28/117 patients (23.9%). Pitted erythrocytes correlated with albumin (p = 0.024), bilirubin (p<0.001), international normalized ratio (INR; p = 0.004), model of end-stage liver disease (MELD) score (p<0.001) and liver stiffness (p = 0.011). Patients with functional hyposplenism had higher MELD scores (median 13 vs. 10; p = 0.021), liver stiffness (46.4 kPa vs. 26.3 kPa; p = 0.011), INR (1.3 vs. 1.2; p = 0.008) and a higher Child-Pugh stage (Child C in 32.1% vs. 11.2%; p = 0.019) as compared to patients without functional hyposplenism. Functional hyposplenism was not associated with the etiology of cirrhosis. Importantly, 9/19 patients with Child C cirrhosis had functional hyposplenism.ConclusionA quarter of patients with liver cirrhosis and almost 50% of patients with Child C cirrhosis have functional hyposplenism. Functional hyposplenism is associated with poor liver function and the degree of portal hypertension, which is characterized by higher liver stiffness measurements in transient elastography.

Objective To study the effect of splenic artery coarctation on liver cirrhosis process in rats and explore the value of splenic artery coarctation.Methods In this study,96 SD rats were randomized into 3 groups:control group,splenectomy group and splenic artery coaretation group.Liver cirrhosis was induced with intraperitoneal injection of thioacetamide.WBC,RBC,PLT,ALT,Alb,T-Bil,hepatic tissue pathology were evaluated among all groups in different phase.Results WBC,RBC,PLT of rats in control group,gradually decreased after surgery (P ＜ 0.05),while that in splenectomy group and splenic artery coarctation group did not change significantly (P ＞ 0.05).Liver function and the severity of liver cirrhosis in splenectomy group and splenic artery coarctation group were less compromised(P ＜ 0.05).Tuftsin level remained about the same in control group and splenic artery coarctation group (P ＞ 0.05),while decreased significandy in rats of splenectomy group (P ＜ 0.05).Conclusions Splenic artery coarctation and splenectomy can prevent hypersplenism and alleviate liver cirrhosis,at the same time splenic artery coarctation reserves the immune function of the spleen. Key words: Liver cirrhosis; Splenic artery; Hypersplenism; Disease models, animal

Cell escape occurs after intramyocardial injection for treatment of myocardial infarction (MI) and then the migrated cells might be entrapped by extracardiac organs. We investigated the fate of migrated bone marrow-derived mesenchymal stromal cells (MSCs) and their impact on lung, liver, and spleen. MI model was created by coronary artery ligation in female Lewis rats. Three weeks after the ligation, bromodeoxyuridine (BrdU)-labeled male MSCs were directly injected into the infarcted area in the cell transplantation group (n = 22). The same volume of phosphate-buffered solution (PBS) was injected in the control group (n = 21). In the sham group (n = 10) intramyocardial injection of the same volume of PBS was performed in healthy rats. Four weeks later, echocardiography was performed and the cell retention was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry study was performed to identify the migrated cells. Heart function was improved after the cell injection. qRT-PCR results showed the percentage of retained cells in heart, spleen, liver, and lung ranked 3.63 ± 0.48%, 0.77 ± 0.13%, 0.68 ± 0.10%, 0.62 ± 0.11%, respectively, after cell transplantation. The implanted MSCs that escaped to liver, spleen, and lung did not differentiate into fibroblast, myofibroblast, or alveolar epithelial cells. However, the migrated MSCs in liver expressed functional hepatocyte marker. In conclusion, cell migration after intramyocardial injection did not result in deterioration of lung, liver, and spleen function. Our study might pave the way for new safety investigation of emerging cell resources and their impact on target and untargeted organs.

Gold nanoparticles (GNPs) are extremely useful for drug delivery, due in part to their highly tunable nature. However, this variability has prevented a clear understanding of the pharmacokinetics and toxicity of GNPs for drug delivery. Here, we present the clearance, organ distribution and acute toxicity testing of our drug delivery system which uses GNPs and two penta-peptides, to deliver a rationally designed peptide drug. We found that with or without our therapeutic, the GNP/peptide hybrid cleared rapidly from the blood in rats and accumulated mostly in the liver and spleen, although it was also detectable in several other organs. There were subtle but detectable differences between the behavior of our GNP hybrids with or without the therapeutic peptide. The GNP/peptide hybrid showed no evidence of toxicity at single doses up to 16 times the therapeutic dose, as measured by a battery of tests including, blood cell makeup, levels of markers of liver, kidney and spleen function, organ mass indexes, and histology. These results underline the importance of testing the pharmacokinetics and toxicity of all GNP preparations, as even minor changes to the surface coatings of GNPs can influence their behavior. On the other hand, the results herein can help guide the design and use of similar GNP/peptide drug delivery systems.

Background: Mesenchymal stem cells (MSCs) have been applied to treat various diseases. Research has shown that hypoxic conditions (2-9% oxygen) that closely reflect the physiological milieu of numerous human tissues, can enhance the biological activities of MSCs in vitro. While many studies highlight the advantages of hypoxic MSCs in vitro, less is known about their effects in vivo. This study assessed the safety of hypoxia-primed MSCs derived from adipose tissues and umbilical cords (AD-MSCs and UC-MSCs, respectively) in healthy animals. Methods: MSCs were isolated from human adipose tissues and umbilical cords, designated as AD-MSCs and UC-MSCs, respectively. These cells were cultured under hypoxic conditions with 5% oxygen to induce priming. For safety evaluation, the primed cells were administered to healthy animal models, including rabbits, Swiss mice, and rats. The safety assessments included analyses of vascular and muscular stimulation, systemic hypersensitivity, acute toxicity, and subchronic toxicity. Results: Our data indicated that UC-MSCs induced vascular stimulation but not muscular stimulation, whereas AD-MSCs caused neither. Additionally, neither AD-MSCs nor UC-MSCs affected hematopoietic parameters (white blood cell, red blood cell, platelet, or hemoglobin levels), altered the levels of proinflammatory cytokines (IL-6, IL-1β, IFN-γ, and TNF-α), or induced allergenic responses in rabbits. Furthermore, intravenous injection of either UC-MSCs or AD-MSCs at a dose of 50 × 106 cells/kg did not cause acute toxicity in mice. However, injections of higher doses of these cells led to intravenous thrombosis and embolism in various organs of experimental animals, ultimately resulting in animal death. Finally, according to the subchronic toxicity assay, the administration of MSCs generally did not impact liver, kidney, or spleen function in rats. Conclusions: Hypoxic MSCs are safe for therapeutic use with consideration of thrombogenic risk and could be alternatives to normoxic MSCs for disease treatment.