Comparison and analysis of soil microbial communities in organic and conventional paddy fields by farming season.

Interest in soil health and biodiversity conservation has become increasingly important. Consequently, studies comparing the chemical and biological characteristics of organic and traditional paddy soils have been increasing. Soil microorganisms are essential in nutrient cycling; however, their diversity is challenging to ascertain because of their environmental sensitivity and complex interactions. Particularly, in domestic rice cultivation, the soil undergoes multiple irrigation and drainage processes during crop growth, providing a diverse ecological environment for soil microorganisms. The objective of this study is to compare the microbial community and diversity between paddy soils in two agricultural systems. We selected organic and conventional paddy fields in Yangpyeong, Gyeonggi Province, and collected monthly samples from August to November 2022 for analysis. Bacteria and fungi were amplified from the 16S rRNA V3V4 region, ITS 3-4 region respectively, For the comparison of microbial diversity, Alpha diversity indices (Chao1, Shannon, Gini-Simpson indices) were analyzed. The results indicated genus-level differences in microbial communities, with the genera Mucor and Sirastachys exclusively present in organic paddy soils, while the genus Ustilaginoidea was exclusively found in conventional paddy soils. Among them, Ustilaginoidea is reported to be a fungus causing false smut disease, causing damage to crop growth and quality. Additionally, the comparison of microbial diversity between the two farming showed no significant differences (p>0.05). In conclusion, When the microbial communities present in both farming systems were examined, organic farming appeared to be more advantageous than conventional farming regarding crop disease and health. This study provides essential soil chemical and microbiological data for understanding the fundamental characteristics of paddy soils in South Korea.

Network Pharmacological Analysis of a New Herbal Combination Targeting Hyperlipidemia and Efficacy Validation In Vitro.

The network pharmacology (NP) approach is a valuable novel methodology for understanding the complex pharmacological mechanisms of medicinal herbs. In addition, various in silico analysis techniques combined with the NP can improve the understanding of various issues used in natural product research. This study assessed the therapeutic effects of Arum ternata (AT), Poria cocos (PC), and Zingiber officinale (ZO) on hyperlipidemia after network pharmacologic analysis. A protein-protein interaction (PPI) network of forty-one key targets was analyzed to discover core functional clusters of the herbal compounds. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology (GO) term enrichment analysis identified significant categories of hypolipidemic mechanisms. The STITCH database indicated a high connection with several statin drugs, deduced by the similarity in targets. AT, PC, and ZO regulated the genes related to the energy metabolism and lipogenesis in HepG2 cells loaded with free fatty acids (FFAs). Furthermore, the mixture of three herbs had a combinational effect. The herbal combination exerted superior efficacy compared to a single herb, particularly in regulating acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase 1 (CPT-1). In conclusion, the network pharmacologic approach was used to assess potential targets of the herbal combination for treatment. Experimental data from FFA-induced HepG2 cells suggested that the combination of AT, PC, and ZO might attenuate hyperlipidemia and its associated hepatic steatosis.

A non-polar fraction of Saponaria officinalis L. acted as a TLR4/MD2 complex antagonist and inhibited TLR4/MyD88 signaling in vitro and in vivo.

Targeting Toll-like receptor 4/myeloid differentiation factor 2 (TLR4/MD2) signaling is regarded as a potential strategy for treating inflammatory diseases. Saponaria officinalis L. is rich in saponin, which include quillaic acid, gypsogenin, saponarin, and hederagenin. We evaluated the pharmacological activity of a Saponaria officinalis extract in THP-1 derived macrophages and RAW264.7 macrophages. TLR4/MyD88 complex formation and downstream signals were investigated by co-immunoprecipitation (Co-IP). In silico docking simulation was conducted to predict binding scores and perform 3D modeling of saponarin-TLR4/MD2 complex. A hexane fraction of Saponaria officinalis (SH) and fr.1 (a sub-fraction 1 of SH) inhibited mitogen-activated protein kinase (MAPK) signaling, nuclear factor kappa b (NF-κB) activity, cytokine production, and the expressions of marker genes specific for M1 polarization. The inhibitory effects of fr.1 and saponarin on TLR4/MyD88 complex formation were observed by western blotting TLR4 co-immunoprecipitated proteins. Saponarin and fr.1 markedly attenuated LPS-induced inflammatory cytokines, thus reducing mortality and morphological abnormality in zebrafish larvae. Finally, docking simulation revealed that saponarin can directly interact with TLR4/MD2 complex to inhibit downstream signalings. Our findings suggest that saponarin reduces downstream inflammatory response by disrupting TLR4/MD2 complex and blocking MyD88-dependent inflammatory signaling.

HSF1 and Its Role in Huntington's Disease Pathology.

PURPOSE OF REVIEW: Heat shock factor 1 (HSF1) is the master transcriptional regulator of the heat shock response (HSR) in mammalian cells and is a critical element in maintaining protein homeostasis. HSF1 functions at the center of many physiological processes like embryogenesis, metabolism, immune response, aging, cancer, and neurodegeneration. However, the mechanisms that allow HSF1 to control these different biological and pathophysiological processes are not fully understood. This review focuses on Huntington's disease (HD), a neurodegenerative disease characterized by severe protein aggregation of the huntingtin (HTT) protein. The aggregation of HTT, in turn, leads to a halt in the function of HSF1. Understanding the pathways that regulate HSF1 in different contexts like HD may hold the key to understanding the pathomechanisms underlying other proteinopathies. We provide the most current information on HSF1 structure, function, and regulation, emphasizing HD, and discussing its potential as a biological target for therapy. DATA SOURCES: We performed PubMed search to find established and recent reports in HSF1, heat shock proteins (Hsp), HD, Hsp inhibitors, HSF1 activators, and HSF1 in aging, inflammation, cancer, brain development, mitochondria, synaptic plasticity, polyglutamine (polyQ) diseases, and HD. STUDY SELECTIONS: Research and review articles that described the mechanisms of action of HSF1 were selected based on terms used in PubMed search. RESULTS: HSF1 plays a crucial role in the progression of HD and other protein-misfolding related neurodegenerative diseases. Different animal models of HD, as well as postmortem brains of patients with HD, reveal a connection between the levels of HSF1 and HSF1 dysfunction to mutant HTT (mHTT)-induced toxicity and protein aggregation, dysregulation of the ubiquitin-proteasome system (UPS), oxidative stress, mitochondrial dysfunction, and disruption of the structural and functional integrity of synaptic connections, which eventually leads to neuronal loss. These features are shared with other neurodegenerative diseases (NDs). Currently, several inhibitors against negative regulators of HSF1, as well as HSF1 activators, are developed and hold promise to prevent neurodegeneration in HD and other NDs. CONCLUSION: Understanding the role of HSF1 during protein aggregation and neurodegeneration in HD may help to develop therapeutic strategies that could be effective across different NDs.

Anti-Inflammatory Effect of Protopine through MAPK and NF-κB Signaling Regulation in HepG2 Cell.

Protopine is a substance used for hemostasis with an anti-inflammatory action and is one of the substances that are actively undergoing experiments to confirm their utility as anticancer agents. This study examined the molecular changes in the cellular signaling pathways associated with inflammatory responses in phorbol 12-myristate 13 acetate (PMA)-induced human hepatocellular carcinoma cell line (Hep G2). The inhibition of PMA-induced phosphorylation of I-κB in HepG2, the effect of protopine on the MAPK signals, the inhibition of COX-2 activity, and the inhibition of MMP-9 as a medium of inflammatory response were evaluated by Western blot and qPCR. The effect of protopine on the survival rates in HepG2 cells was evaluated and found to be stable to a processing concentration of up to 40µM. Subsequent Western blot analyses showed that protopine blocks the transfer of the MAPKs cell signals induced by PMA and the transfer of the subunit of the nuclear factor-kappa B (NF-κB) to the nucleolus. Protopine inhibited the kappa alpha (I-κBα) phosphorylation in the cytosol and blocked PMA-induced inflammation via COX-2 activity inhibition. The expression of MMP-9 at the gene and protein levels, which is associated with cell migration and metastasis, was reduced by protopine.

Cortical Neuron Migration and Dendrite Morphology are Regulated by Carboxypeptidase E.

Higher brain function relies on proper development of the cerebral cortex, including correct positioning of neurons and dendrite morphology. Disruptions in these processes may result in various neurocognitive disorders. Mutations in the CPE gene, which encodes carboxypeptidase E (CPE), have been linked to depression and intellectual disability. However, it remains unclear whether CPE is involved in early brain development and in turn contributes to the pathophysiology of neurocognitive disorders. Here, we investigate the effects of CPE knockdown on early brain development and explore the functional significance of the interaction between CPE and its binding partner p150Glued. We demonstrate that CPE is required for cortical neuron migration and dendrite arborization. Furthermore, we show that expression of CPE-C10 redistributes p150Glued from the centrosome and that disruption of CPE interaction with p150Glued leads to abnormal neuronal migration and dendrite morphology, suggesting that a complex between CPE and p150Glued is necessary for proper neurodevelopment.

Phytoavailability-based threshold values for cadmium in soil for safer crop production.

The phytoavailability of heavy metals in soils is important for both food safety and environmental management. Hence soil metal phytoavailability threshold values need to be established based on a firm scientific basis. In this study, optimal Cd phytoavailability threshold values, were determined for bean, rice and sesame cultivated in 100 soils varying widely in soil chemical characteristics by comparing the soil Cd phytoavailability obtained using three commonly used extraction procedures. Subsequently, the transfer functions derived in this study, were used to establish soil Cd phytoavailability threshold value standard limits for each specific crop. In addition, independent experimental data were used to supplement the obtained soil phytoavailable Cd threshold value for rice. Soil phytoavailable Cd concentrations extracted by 1 M NH4NO3, 0.05 M EDTA and Mehlich3 solutions were each more significantly correlated with plant Cd concentrations than total soil Cd concentrations. Thus, the soil Cd phytoavailability threshold values proposed in this study provide a more effective means of ensuring safer agricultural food production. Therefore, it is recommended that current agricultural soil heavy metal management policy; which is based on total concentrations; should be changed to embrace soil metal phytoavailability for safer agricultural food production.

Incidence and Mortality Rates of Thoracic Aortic Dissection in Korea - Inferred from the Nationwide Health Insurance Claims.

BACKGROUND: Aortic dissection (AD) is one of the most catastrophic diseases and is associated with high morbidity and mortality. The aim of this study is to investigate the hospital incidence and mortality rates of thoracic AD in Korea using a nationwide database. METHODS: We conducted a nationwide population-based study using the health claims data of the National Health Insurance Service in Korea. From 2005 to 2016, adult patients newly diagnosed with AD were included. All patients were divided into the following four subgroups by treatment: type A surgical repair (TASR), type B surgical repair (TBSR), thoracic endovascular aortic repair (TEVAR), and medical management (MM). The incidence rate, mortality rate, and risk factors of in-hospital mortality were evaluated. RESULTS: In total, 18,565 patients were newly diagnosed with AD (TASR, n = 4,319 [23.3%]; TBSR, n = 186 [1.0%]; TEVAR, n = 697 [3.8%]; MM, n = 13,363 [72.0%]). The overall AD incidence rate was 3.76 per 100,000 person-years and exhibited a gradual increase during the study period (3.29 to 4.82, P < 0.001). The overall in-hospital mortality rate was 10.84% and remained consistent (P = 0.57). However, the in-hospital mortality rate decreased in the TASR subgroup (18.23 to 11.27%, P = 0.046). An older age, the female sex, hypertension, and chronic kidney disease were independent risk factors for in-hospital mortality. CONCLUSION: The incidence of thoracic AD has gradually increased in Korea. The in-hospital mortality in the TASR subgroup decreased over the decade, although the overall mortality of AD patients did not change.

Off-Pump Coronary Artery Bypass Graft Versus Drug-Eluting Stent Implantation in Patients with Multivessel Disease Involving the Right Coronary Artery.

BACKGROUND: Whether percutaneous coronary intervention (PCI) is superior to coronary artery bypass grafting (CABG) for the right coronary territory is unknown. The aim of this study was to compare the outcomes and patency in the right coronary territory after CABG or PCI. METHODS: We studied 2,467 multivessel coronary artery disease patients from January 2001 to December 2011; 1,672 were off-pump CABG patients and 795 were PCI. The graft patency and the presence of major adverse cardiac and cerebrovascular events (MACCEs) including death, myocardial infarction, target vessel revascularization, and stroke were analyzed. RESULTS: After propensity score matching, cardiac-related survival was found to be significantly higher in the CABG group than in the PCI group (hazard ratio (HR) for the PCI group: 2.445, p = 0.006). The PCI group showed higher rates of myocardial infarction (HR: 2.571, p = 0.011) and target vessel revascularization (HR: 3.337, p < 0.001). In the right coronary territory, the right internal thoracic artery patency was not different in the PCI group compared with the CABG group (p = 0.248). In CABG group, low right coronary artery graft patency was associated with cardiac-related death (HR: 0.17, p = 0.003) and the occurrence of MACCEs (HR: 0.22, p < 0.001). CONCLUSION: CABG was superior to PCI in patients with multivessel disease. Low graft patency in the right coronary territory was associated with cardiac-related death and the occurrence of MACCEs.

A DOC coagulant, gypsum treatment can simultaneously reduce As, Cd and Pb uptake by medicinal plants grown in contaminated soil.

The efficiency of gypsum, as a dissolved organic carbon (DOC) coagulator, for the simultaneous immobilization of two heavy metals (Cd and Pb) and one metalloid (As) in agricultural soils near an abandoned mining site was examined. The agricultural soil was defined as long-term contaminated as As (1540mgkg-1), Cd (55mgkg-1) and Pb (1283mgkg-1) concentrations exceeded the Korean guideline values for As (25mgkg-1), Cd (4mgkg-1), and Pb (200mgkg-1). Gypsum was incorporated into the contaminated soil at 3% (w/w). In comparison two commonly using immobilizing agents (lime and compost), together with a mixture (lime+gypsum) were also included in the pot trial for the cultivation of two medical plants (A. gigas and A. macrocephala) and to evaluate the effectiveness of gypsum on As, Cd and Pb immobilization. The results showed that even though pH change-induced immobilizing agents such as lime were more effective than gypsum at immobilizing Cd and Pb, addition of gypsum also effectively reduced heavy metal phytoavailability as indicated by decreases in the concentration of Cd and Pb in medicinal plants. Furthermore, gypsum and gypsum+ lime were also most effective in reducing As concentrations in both plants studied. This was mainly attributed to significant decreases in soil DOC (48-64%) when gypsum and gypsum+lime were applied to the soil. Consequently, it was concluded that enhanced DOC coagulation with gypsum, could be considered as a promising technique for the immobilization of both metals (Cd and Pb) and metalloids (As) in agricultural soils.

Influence of Road Proximity on the Concentrations of Heavy Metals in Korean Urban Agricultural Soils and Crops.

The urban agricultural (UA) environment near active roadways can be degraded by traffic-related particles (i.e., exhaust gases and road dust), which may contain heavy metals. The current study investigated changes in heavy-metal [cadmium (Cd), copper (Cu), chromium (Cr) nickel (Ni), lead (Pb) and zinc (Zn)] concentrations in soils located near highly trafficked roads in Korea and the subsequent uptake of these metals by Chinese cabbage. Heavy-metal plant concentrations were determined in both washed and unwashed plant leaves to determine whether foliar deposition played any role in plant metal uptake. Soil concentrations of Cd, Cu, Pb, and Zn were all lower than the Korean standard soil limits and showed no significant influence from road traffic. In contrast, both Ni and Cr concentrations in soils collected within 10 m of the road were 4 and 5 times greater, respectively, than those in soils collected 70 m from the road. Heavy-metal concentrations in unwashed Chinese cabbage leaf collected at 5 m from the road were consistently greater than those of washed leaf samples, thus indicating the deposition of traffic-related particles on the plant surface. With the exception of Cu, all heavy-metal concentration in washed plant samples collected at 5 m also showed greater accumulation compared with samples collected further away. This was mainly attributed to increased total soil heavy-metal concentrations and increased metal phytoavailability induced by decreases in soil pH near the road. However, overall heavy-metal soil concentrations were well lower than the allowable concentrations, and the levels observed in plants collected in this study were considered not to currently pose a significant risk to human health. However, some traffic-related heavy metals, in particular Cr and Ni, were being accumulated in the roadside UA environment, which may warrant some caution regarding the environment and/or health issues in the future.

The Effects of Granulocyte-Colony Stimulating Factor on Regeneration in Nerve Crush Injuries in Rats.

Granulocyte-colony stimulating factor (G-CSF) is widely known to have a neuroprotective effect, but its effects on function and morphology in mechanical nerve injury are not well understood. The aim of this study was to confirm the time course of the functional changes and morphological effects of G-CSF in a rat model of nerve crush injury. Twelve-eight rats were divided into three group: sham-operated control group, G-CSF-treated group, and saline treated group. 2 weeks after the nerve crush injury, G-CSF was injected for 5 days. After 4 weeks, functional tests such as motor nerve conduction velocity (MNCV), mechanical and cold allodynia tests, and morphological studies were performed. G-CSF-treated rats had significantly improved nerve function including MNCV and mechanical and cold allodynia. In addition, G-CSF-treated rats had significantly higher the density of myelinated fibers than saline-treated rats. In conclusion, we found that 100 µg/kg administration of G-CSF promoted long-term functional recovery in a rat model of nerve crush injury.

An integrated approach to safer plant production on metal contaminated soils using species selection and chemical immobilization.

In order to examine the species specific accumulation of heavy metals in medicinal crops, seven different common medicinal plants were cultivated on a Cd (55mgkg(-1)) and Pb (1283mgkg(-1)) contaminated soil. Subsequently, the effect of various immobilizing agents, applied in isolation and in combination, on Cd and Pb uptake by two medicinal plant species was examined. Cadmium and Pb root concentrations in medicinal plants grown in the control soil varied between 0.5 and 2.6mgkg(-1) for Cd and 3.2 and 36.4mgkg(-1) for Pb. The highest accumulation occurred in Osterici Radix (Ostericum koreanum) and Ginger (Zingiber officinale) and the lowest in Yam (Dioscorea batatas). Application of immobilizing agents significantly reduced both Cd and Pb concentrations in all medicinal plants examined, where the most effective single immobilizing agent was lime fertilizer (LF). Application of combination treatments involving sorption agents such as compost together with lime further decreased Cd and Pb concentrations from 1.3 and 25.3mgkg(-1) to 0.2 and 4.3mgkg(-1), respectively, which was well below the corresponding WHO guidelines. Thus appropriate immobilizing agents in combination with species selection can be practically used for safer medicinal plant production.

Bo-Gan-Whan regulates proliferation and migration of vascular smooth muscle cells.

BACKGROUND: Bo-Gan-Whan (BGH), a Korean polyherbal medicine, is used as a hepatoprotective drug. It has six natural sources, and has been demonstrated to have anti-oxidative, anti-cancer, and anti-inflammatory properties; however, its effect on vascular diseases remains unclear. METHODS: Cell viability and proliferation assays were employed using an EZ-Cytox Cell Viability Assay Kit. Platelet-derived growth factor (PDGF)-BB-induced vascular smooth muscle cell (VSMC) migration was measured by scratch wound healing assay and Boyden chamber assay. The expression levels of the phosphorylated signaling proteins relevant to proliferation, including extracellular signal-regulated kinase (ERK) 1/2 and p38 mitogen-activated protein kinase (MAPK) were determined by western blot analysis. Chromatogram and mass analysis were employed by Ultra Performance Liquid Chromatography (UPLC) system. Cell prolife ration and migration were also explored using the PDGF-BB-induced aortic sprout assay. RESULTS: BGH (100-500 µg/mL) significantly inhibited the proliferation and migration of PDGF-BB-stimulated VSMCs through the reduced phosphorylation of ERK1/2 and p38 MAPK in comparison to untreated PDGF-BB-stimulated VSMC. Moreover, we identified the paeoniflorin as the major composition of BGH. CONCLUSIONS: We suggest that BGH may have an anti-atherosclerosis effect by inhibiting the proliferation and migration of PDGF-BB-stimulated VSMCs through down-regulation of ERK1/2 and p38 MAPK phosphorylation.

Amomum cardamomum L. ethyl acetate fraction protects against carbon tetrachloride-induced liver injury via an antioxidant mechanism in rats.

BACKGROUND: Medicinal herb-derived drug development has become important in the relief of liver pathology. Amomun cardamomum is traditionally used therapeutically in Korea to treat various human ailments including dyspepsia, hiccupping, and vomiting. We investigated to assess the protective effect of A. cardamomum on carbon tetrachloride (CCl4)-induced liver damage through antioxidant activity in hepatic tissues of Sprague-Dawley rats. METHODS: Antioxidant properties of different fractions from A. cardamomum from ethanol extracts were evaluated by an in vitro free radical scavenging systems. The protective effect of the ethyl acetate fraction from A. cardamomum (EAAC) against CCl4-induced cytotoxicity was determined by a cell viability assay using HepG2 hepatocarcinoma cells. In vivo study, the influence of EAAC concentrations of 100 and 200 mg/kg following CCl4-induced hepatic injury was assessed. Serum levels of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and alkaline phosphatase (ALP) were determined, as was lipid peroxidation (malondialdehyde, MDA). Effect of EAAC on liver detoxification enzymes including superoxide dismutase (SOD), total glutathione (GSH), and glutathione S-transferase (GST) activity was measured in rat liver homogenates. Liver cytochrome P450 (CYP2E1) expression level was determined by quantification of mRNA. RESULTS: Phytochemical analysis of A. cardamomum indicated that EAAC was enriched in total polyphenol and total flavonoid. Most of the tannins were confined to the hexane fraction. Hepatoprotective properties of EAAC were evident, with significantly reduced serum levels of GOT, GPT, and ALP compared with the control group. Improved hepatic antioxidant status was evident by increased SOD, GSH, and GST enzymes in rat liver tissue. Liver lipid peroxidation induced by CCl4 was apparent by increased intracellular MDA level. EAAC suppressed lipid peroxidation as evidenced by the significant decrease in MDA production. Expression of CYP2E1 was also significantly decreased at the higher concentration of EAAC, indicating the hepatoprotective efficacy of EAAC on acute liver damage. CONCLUSION: These results indicated that EAAC has a significant hepatoprotective activity on CCl4-induced acute hepatic injury in rats, which might be derived from its antioxidant properties and CYP2E1 downregulation.

Granulocyte-colony stimulating factor prevents the development of hepatic steatosis in rats.

BACKGROUND AND AIMS: Previously, we reported that granulocyte-colony stimulating factor (G-CSF) improves hepatic steatosis in experimental animals. It may also have preventive effects on the development of hepatic steatosis. Therefore, we investigated the preventive effects of G-CSF by using a high-fat diet (HFD) rat model. MATERIALS AND METHODS: Twelve rats were fed HFD and 6 rats were fed control diet from 10 weeks of age. Once little steatosis was confirmed in the liver (after 10 weeks of feeding the HFD; at 20 weeks of age), HFD rats were randomly divided into two groups and treated with either G-CSF (100 µg kg-1 day-1 for 5 consecutive days every other week; HFD/G-CSF rats) or saline (HFD/saline rats) for 10 weeks at 20 weeks of age. All rats were sacrificed at 30 weeks of age. Histology was examined by hematoxylin and eosin (H-E) and Oil Red O staining, and the expression levels of genes of associated with lipogenesis and ß-oxidation enzymes were determined by qRT-PCR. RESULTS: Histological examinations revealed that HFD/G-CSF rats had significantly lower lipid accumulation in their hepatocytes than did HFD/saline rats (p < 0.05). HFD/G-CSF rats also showed lower expression levels of genes associated with lipogenesis and higher expression levels of genes associated with ß-oxidation than HFD/saline rats (p < 0.05). CONCLUSION: In conclusion, we found that G-CSF prevented development of hepatic steatosis in an HFD rat model. The preventive effect may be associated with the regulation of gene expression involved in hepatic lipogenesis and ß-oxidation.

Histopathological analyses of diabetic nephropathy in sucrose-fed Otsuka Long-Evans Tokushima fatty rats.

BACKGROUND: Otsuka Long-Evans Tokushima fatty (OLETF) rats are an established model of diabetic nephropathy. However, diabetes and diabetic nephropathy (DN) in OLETF rats develop later than in other animal type 2 diabetes models. OBJECTIVES: This study was conducted to investigate the serial changes in the histopathological characteristics of DN in sucrose-fed OLETF rats by biochemical and morphometric analyses. METHODS: We conducted sucrose feeding to examine the progression of DN. One group of OLETF rats was given water containing 30% sucrose ad libitum (SO) and the other group was given water without 30% sucrose (TO). Consecutive observations were made at 4-week intervals from 16 to 50 weeks of age in TO rats, and from 16 to 42 weeks of age in SO rats. Examination parameters included body weight, serum glucose level, urine albumin-to-creatinine ratio (UACR), light microscopy (LM) and electron microscopy (EM). RESULTS: The UACR was over 300 mg/g in 32-week-old SO rats (after 16 weeks of sucrose feeding) and in 38-week-old TO rats. LM indicated that glomerular hypertrophy and mesangial matrix expansion in SO rats increased compared to that of age-matched TO rats especially at 42 weeks of age (p < 0.05). EM also showed that glomerular basement membrane thickness and podocyte foot process width of SO rats were significantly greater than those of age-matched TO rats (p < 0.05). CONCLUSION: Our results suggested that dietary manipulation by sucrose feeding may cause deterioration of DN and could hasten the onset of diabetes and DN in OLETF rats.

Inherited genetic variants in autism-related CNTNAP2 show perturbed trafficking and ATF6 activation.

Although genetic variations in several genes encoding for synaptic adhesion proteins have been found to be associated with autism spectrum disorders, one of the most consistently replicated genes has been CNTNAP2, encoding for contactin-associated protein-like 2 (CASPR2), a multidomain transmembrane protein of the neurexin superfamily. Using immunofluorescence confocal microscopy and complementary biochemical techniques, we compared wild-type CASPR2 to 12 point mutations identified in individuals with autism. In contrast to the wild-type protein, localized to the cell surface, some of the mutants show altered cellular disposition. In particular, CASPR2-D1129H is largely retained in the endoplasmic reticulum (ER) in HEK-293 cells and in hippocampal neurons. BiP/Grp78, Calnexin and ERp57, key ER chaperones, appear to be responsible for retention of this mutant and activation of one signaling pathway of the unfolded protein response (UPR). The presence of this mutation also lowers expression and activates proteosomal degradation. A frame-shift mutation that causes a form of syndromic epilepsy (CASPR2-1253*), results in a secreted protein with seemingly normal folding and oligomerization. Taken together, these data indicate that CASPR2-D1129H has severe trafficking abnormalities and CASPR2-1253* is a secreted soluble protein, suggesting that the structural or signaling functions of the membrane tethered form are lost. Our data support a complex genetic architecture in which multiple distinct risk factors interact with others to shape autism risk and presentation.

Granulocyte-colony stimulating factor reduces cardiomyocyte apoptosis and ameliorates diastolic dysfunction in Otsuka Long-Evans Tokushima Fatty rats.

BACKGROUND: In recent studies, granulocyte-colony stimulating factor (G-CSF) was shown to improve cardiac function in myocardial infarction and non-ischemic cardiomyopathies. The mechanisms of these beneficial effects of G-CSF in diabetic cardiomyopathy are not yet fully understood. Therefore, we investigated the mechanisms of action of G-CSF on diabetic cardiomyopathy in a rat model of type 2 diabetes. METHODS: Seventeen-week-old OLETF (Otsuka Long Evans Tokushima Fatty) diabetic rats and LETO (Long Evans Tokushima Otuska) rats were randomized to treatment with 5 days of G-CSF (100 µg/kg/day) or with saline. Cardiac function was evaluated by serial echocardiography performed before and 4 weeks after treatment. We measured expression of the G-CSF receptor (GCSFR) and Bcl-2, as well as the extent of apoptosis in the myocardium. RESULTS: G-CSF treatment significantly improved cardiac diastolic function in the serial echocardiography assessments. Expression of G-CSFR was down-regulated in the diabetic myocardium (0.03 ± 0.12 % vs. 1 ± 0.15 %, p < 0.05), and its expression was stimulated by G-CSF treatment (0.03 ± 0.12 % vs. 0.42 ± 0.06 %, p < 0.05). In addition, G-CSF treatment increased the expression of Bcl-2 in the diabetic myocardium (0.69 ± 0.06 % vs. 0.26 ± 0.11 %, p < 0.05), consistent with the reduced cardiomyocyte apoptosis (9.38 ± 0.67 % vs. 17.28 ± 2.16 %, p < 0.05). CONCLUSIONS: Our results suggest that G-CSF might have a cardioprotective effect in diabetic cardiomyopathy through up-regulation of G-CSFR, attenuation of apoptosis by up-regulation of Bcl-2 expression, and glucose-lowering effect. Our findings support the therapeutic potential of G-CSF in diabetic cardiomyopathy.

Biatrial myxoma and multiple organ infarctions combined with Leriche syndrome in a female patient.

BACKGROUND: Multiple organ infarctions combined with Leriche syndrome due to embolic particles of myxoma are very rare. There is no definite guideline for immediate medical treatment. CASE PRESENTATION: A 36-year-old married female was referred to the emergency department (ED) with severe pain of both lower extremities and gradual decreased mental status. Brain magnetic resonance imaging (MRI) and computed tomography angiography (CTA) revealed acute multiple organ infarctions including the brain, spleen, and bilateral kidneys combined with Leriche syndrome. To evaluate the embolic source, echocardiography was performed and it revealed biatrial myxoma. Because of the risk of progression in systemic embolic events, surgical excision and embolectomy were performed urgently. After the operation, renal function was recovered, and the pain of both limbs was relieved. However, the visual field defect due to the brain infarction remained. She was discharged uneventfully on the fourteenth postoperative day. CONCLUSION: This was an extremely rare case of multiple organ infarctions combined with Leriche syndrome as the initial presentation of biatrial myxoma. The treatment of choice for myxoma is surgical excision, but the optimal timing of operations is still controversial in patients who have had recent neurological insults. Echocardiography was useful to clarify the diagnosis and decide on the proper treatment modality: surgical treatment or thrombolysis.