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Summary Haplo-insufficiency of telomerase genes in humans leads to telomere syndromes such as dyskeratosis congenital and idiopathic pulmonary fibrosis. Generation of pluripotent stem cells from telomerase haplo-insufficient donor cells would provide unique opportunities toward the realization of patient-specific stem cell therapies. Recently, pluripotent human embryonic stem cells (ntESCs) have been efficiently achieved by somatic cell nuclear transfer (SCNT). We tested the hypothesis that SCNT could effectively elongate shortening telomeres of telomerase haplo-insufficient cells in the ntESCs with relevant mouse models. Indeed, telomeres of telomerase haplo-insufficient ( Terc +/− ) mouse cells are elongated in ntESCs. Moreover, ntESCs derived from Terc +/− cells exhibit naive pluripotency as evidenced by generation of Terc +/− ntESC clone pups by tetraploid embryo complementation, the most stringent test of naive pluripotency. These data suggest that SCNT could offer a powerful tool to reprogram telomeres and to discover the factors for robust restoration of telomeres and pluripotency of telomerase haplo-insufficient somatic cells. [ABSTRACT FROM AUTHOR]

Background/Purpose The collection of exhaled breath condensate (EBC) is a noninvasive method that can be used to monitor the inflammatory status of patients with chronic airway diseases. We aimed to study differences in cytokine expression between patients with exacerbations of chronic obstructive pulmonary disease (COPD) and patients with asthma attacks. Methods Using a custom-made device and methods based on American Thoracic Society (ATS)/European Respiratory Society (ERS) recommendations, EBC samples were collected from nine COPD patients, 12 asthma patients and 10 healthy individuals. Cytokine concentrations in serum and EBC were measured via commercial ELISA kits. Results Of four cytokines measured in EBC [interleukin-8 (IL-8), IL-17, IL-4 and tumor necrosis factor-α (TNF-α)], only IL-8 was significantly higher in COPD than in asthma patients (5.27 ± 0.18 vs. 4.36 ± 0.34 pg/mL, p = 0.001). Moreover, COPD patients had higher serum IL-8 than asthma patients (10.57 ± 0.55 vs. 5.15 ± 0.24 pg/mL, p < 0.001). No significant correlation between serum and EBC cytokine concentrations was observed in each subgroup of patients. Conclusion Compared with patients with asthma attacks, patients with exacerbated COPD had increased IL-8 expression in both serum and EBC. These results suggest that IL-8 may be more important in airway and systemic inflammation in COPD exacerbations than in asthma attacks. [ABSTRACT FROM AUTHOR]

PURPOSE: Antrodia camphorata (AC), a highly valued polypore mushroom native only to Taiwan, has been traditionally used as a medicine for the treatment of food and drug intoxication, diarrhea, abdominal pain, hypertension, skin itching, and cancer. In this study, both of solid-state-cultured AC (S-AC) and wood-cultured AC (W-AC) were evaluated the anti-inflammatory effects on hyperoxia-induced lung injury in NF-[kappa]B-luciferase(+/+) transgenic mice. METHODS: The homozygous transgenic mice (NF-[kappa]B-luciferase(+/+)) were randomly assigned to four groups for treatment (n=6) including Normoxia/DMSO group, Hyperoxia/DMSO group, Hyperoxia/S-AC group, and Hyperoxia/W-AC group. After 72h of hyperoxia, we examined the bioluminescence images, reactive oxygen species (ROS), the mRNA and protein expression levels of inflammation factors, and histopathological analyses of the lung tissues. RESULTS: Hyperoxia-induced lung injury significantly increased the generation of ROS, the mRNA levels of IL-6, TNF-[alpha], IL-1[beta] and IL-8, and the protein expression levels of IKK[alpha]/[beta], iNOS and IL-6. Pulmonary edema and alveolar infiltration of neutrophils was also observed in the hyperoxia-induced lung tissue. However, treatment with either S-AC or W-AC obviously decreased hyperoxia-induced generation of ROS and the expression of IL-6, TNF-[alpha], IL-1[beta], IL-8, IKK[alpha]/[beta] and iNOS compared to hyperoxia treatment alone. Lung histopathology also showed that treatment with either S-AC or W-AC significantly reduced neutrophil infiltration and lung edema compared to treatment with hyperoxia treated alone. To find out their major compounds, eburicoic acid and dehydroeburicoic acid were both isolated and identified from S-AC and W-AC by using HPLC, MS, and NMR spectrometry. CONCLUSIONS: These results demonstrated that methanolic extracts both of S-AC and W-AC have excellent anti-inflammatory activities and thus have great potential as a source for natural health products. [ABSTRACT FROM AUTHOR]

Purpose Antrodia camphorata (AC), a highly valued polypore mushroom native only to Taiwan, has been traditionally used as a medicine for the treatment of food and drug intoxication, diarrhea, abdominal pain, hypertension, skin itching, and cancer. In this study, both of solid-state-cultured AC (S-AC) and wood-cultured AC (W-AC) were evaluated the anti-inflammatory effects on hyperoxia-induced lung injury in NF-κB-luciferase +/+ transgenic mice. Methods The homozygous transgenic mice (NF-κB-luciferase +/+ ) were randomly assigned to four groups for treatment ( n = 6) including Normoxia/DMSO group, Hyperoxia/DMSO group, Hyperoxia/S-AC group, and Hyperoxia/W-AC group. After 72 h of hyperoxia, we examined the bioluminescence images, reactive oxygen species (ROS), the mRNA and protein expression levels of inflammation factors, and histopathological analyses of the lung tissues. Results Hyperoxia-induced lung injury significantly increased the generation of ROS, the mRNA levels of IL-6 , TNF-α , IL-1β and IL-8 , and the protein expression levels of IKKα/β, iNOS and IL-6. Pulmonary edema and alveolar infiltration of neutrophils was also observed in the hyperoxia-induced lung tissue. However, treatment with either S-AC or W-AC obviously decreased hyperoxia-induced generation of ROS and the expression of IL-6, TNF-α, IL-1β, IL-8, IKKα/β and iNOS compared to hyperoxia treatment alone. Lung histopathology also showed that treatment with either S-AC or W-AC significantly reduced neutrophil infiltration and lung edema compared to treatment with hyperoxia treated alone. To find out their major compounds, eburicoic acid and dehydroeburicoic acid were both isolated and identified from S-AC and W-AC by using HPLC, MS, and NMR spectrometry. Conclusions These results demonstrated that methanolic extracts both of S-AC and W-AC have excellent anti-inflammatory activities and thus have great potential as a source for natural health products. [ABSTRACT FROM AUTHOR]

Multidrug-resistant (MDR) cancer is a major clinical problem in chemotherapy of cancer patients. We have noted inappropriate PKCδ hypomethylation and overexpression of genes in the PKCδ/AP-1 pathway in the human uterus sarcoma drug-resistant cell line, MES-SA/Dx5 cells, which also overexpress p-glycoprotein (ABCB1). Recent studies have indicated that FZD1 is overexpressed in both multidrug-resistant cancer cell lines and in clinical tumor samples. These data have led us to hypothesize that the FZD1-mediated PKCδ signal-transduction pathway may play an important role in drug resistance in MES-SA/Dx5 cells. In this work, the PKCδ inhibitor Rottlerin was found to reduce ABCB1 expression and to inhibit the MDR drug pumping ability in the MES-SA/Dx5 cells when compared with the doxorubicin-sensitive parental cell line, MES-SA. PKCδ was up-regulated with concurrent up-regulation of the mRNA levels of the AP-1-related factors, c-JUN and c-FOS. Activation of AP-1 also correlated with up-regulation of the AP-1 downstream genes HGF and EGR1. Furthermore, AP-1 activities were reduced and the AP-1 downstream genes were down-regulated in Rottlerin-treated or PKCδ shRNA-transfected cells. MES-SA/Dx5 cells were resensitized to doxorubicin-induced toxicity by co-treatment with doxorubicin and Rottlerin or PKCδ shRNA. In addition, cell viability and drug pump-out ability were significantly reduced in the FZD1 inhibitor curcumin-treated and FZD1 shRNA-knockdown MES-SA/Dx5 cells, indicating involvement of PKCδ in FZD1-modulated ABCB1 expression pathway. Taken together, our data demonstrate that FZD1 regulates PKCδ, and the PKCδ/AP-1 signalling transduction pathway plays an important role in drug resistance in MES-SA/Dx5 cells. [ABSTRACT FROM AUTHOR]

Abstract: In this study, the bone structures, nanomechanical properties and fracture behaviors in different groups of female C57BL/6 mice (control, sham operated, ovariectomized, casein supplemented, and fermented milk supplemented) were examined by micro-computed tomography, scanning and transmission electron microscopy, and nanoindentation. The control and sham operated mice showed dense bone structures with high cortical bone mineral densities of 544 mg/cm3 (average) and high hardness of 0.9–1.1 GPa; resistance to bone fracture was conferred by microcracking, crack deflections and ligament bridging attributed to aligned collagen fibers and densely packed hydroxyapatite crystals. Bone mineral density, hardness and fracture resistance in ovariectomized mice markedly dropped due to loose bone structure with randomly distributed collagens and hydroxyapatites. The acidic casein supplemented mice with blood acidosis exhibited poor mineral absorption and loose bone structure, whereas the neutralized casein or fermented milk supplemented mice were resistant to osteoporosis and had high bone mechanical properties. [Copyright &y& Elsevier]

Abstract: Many factors have been implicated in the onset of type 2 diabetes mellitus (T2DM). Recently, immune response and inflammation were suggested to play certain roles in the development and complications of T2DM. The aim of this study is to investigate the putative correlation between the promoter polymorphisms of interleukin-4 (IL-4), one of the immune-regulatory type 2 helper T-cell cytokines, and T2DM. Genomic DNA from 425 Taiwanese T2DM patients and 148 nondiabetic control study subjects were extracted, and their IL-4 promoter polymorphisms were analyzed by polymerase chain reaction–restriction fragment length polymorphism. Both of the distribution of IL-4 C-589T (P = .013) and C-34T (P = .05) genotypes were significantly different between T2DM patients and control subjects. Significant association between IL-4 C-589T alleles (P = .002) and T2DM, as well as C-34T alleles and T2DM (P =.024), was also identified. In addition, a statistically significant association between homologous IL-4 −589 C/C genotype and lower circulatory high-density lipoprotein cholesterol levels was observed. Our results suggested that IL-4 promoter polymorphisms are associated with T2DM. A significant association between IL-4 −589 C/C genotype and lower circulatory high-density lipoprotein cholesterol level was observed as well. The above results suggested that IL-4 may participate in lipid metabolism and diabetic susceptibility. [ABSTRACT FROM AUTHOR]

Background: The association between psoriasis and cardiovascular diseases is well documented yet the underlying mechanisms remain elusive. Objectives: We sought to study the role of circulating osteopontin (OPN) in the pathogenesis of cardiovascular diseases in patients with psoriasis. Methods: Plasma samples from 40 patients with psoriasis and 37 control subjects were collected for enzyme-linked immunosorbent assays. The clinical significance of OPN levels in patients with psoriasis versus control subjects was analyzed using the Mann-Whitney U test and logistic regression. DNA samples from 268 patients with psoriasis and 146 control subjects were collected for genotyping of the OPN gene. Results: Higher body mass index values (P = .047) and hypertension (odds ratio [OR] 2.68, P = .05) were observed in patients with psoriasis. Increased plasma OPN levels (≥62.95 ng/mL) were significantly associated with psoriasis (OR 6.24, P = .001), hypertension (OR 3.05, P = .03), and diabetes mellitus (OR 3.13, P = .05). Occurrence of psoriasis (OR 5.12, P = .003) appeared to be the single independent risk factor for high plasma OPN values after multivariate logistic regression. Among patients with psoriasis, increased plasma OPN values were associated with the presence of hypertension (OR 4.69, P = .05). However, no significantly different allelic distributions of single nucleotide polymorphisms of the OPN gene were found between psoriasis and control groups. Limitations: The number of patients evaluated was relatively small. Conclusions: High plasma OPN levels are an unfavorable factor for development of cardiovascular disease in patients with psoriasis. [Copyright &y& Elsevier]

Differential methylation hybridization (DMH) is a high-throughput microarray technique designed to identify changes in DNA methylation patterns commonly observed in cancer and other disease states. The DMH methodology comprises three fundamental components: the arraying of CpG island clones on glass slides, the preparation of the sample amplicons under investigation, and the hybridization of amplicon targets onto the CpG island microarray. Herein, we outline the DMH protocol and illustrate its utility and the validation approaches used in analyzing the hypermethylation profile of breast tumor and normal samples. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is a devastating neurodegenerative disorder characterized by the accumulation of mutant Huntingtin protein (mHTT) and oxidative stress-induced neuronal damage. Based on previous reports, microRNA-196a (miR-196a) has emerged as a potential therapeutic target due to its neuroprotective effects in various neurodegenerative diseases. However, whether miR-196a functions through antioxidative effects is still unknown. In this study, we demonstrated that HD models, both in vitro and in vivo , exhibit elevated levels of reactive oxygen species (ROS) and increased neuronal death, and miR-196a mitigates ROS levels and reduces cell death in HD cells. Moreover, we elucidated that miR-196a facilitates the translocation of nuclear factor erythroid 2 (Nrf2) into the nucleus, enhancing the transcription of antioxidant genes, including heme oxygenase-1 (HO-1). We further identified ubiquitin-specific peptidase 15 (USP15), a direct target of miR-196a related to the Nrf2 pathway, and USP15 exacerbates mHTT aggregate formation while partially counteracting miR-196a-induced reductions in mHTT levels. Taken together, these findings shed light on the multifaceted role of miR-196a in HD, highlighting its potential as a therapeutic avenue for ameliorating oxidative stress and neurodegeneration in this debilitating disease. [Display omitted] • Huntington's disease displays higher level of ROS and cell death. • MiR-196a reduces ROS levels and mitigates cell death in HD models. • MiR-196a enhances Nrf2 translocation to activate antioxidant gene transcription. • MiR-196a suppresses USP15 directly to affect Nrf2 signaling. • USP15 accelerates the formation of mHTT aggregates. [ABSTRACT FROM AUTHOR]

Liver fibrosis is a chronic liver disease caused by prolonged liver injuries. Excessive accumulation of extracellular matrix replaces the damaged hepatocytes, leading to fibrous scar formation and fibrosis induction. Lactoferrin (LF) is a glycoprotein with a conserved, monomeric signal polypeptide chain, exhibiting diverse physiological functions, including antioxidant, anti-inflammatory, antibacterial, antifungal, antiviral, and antitumoral activities. Previous study has shown LF's protective role against chemically-induced liver fibrosis in rats. However, the mechanisms of LF in liver fibrosis are still unclear. In this study, we investigated LF's mechanisms in thioacetamide (TAA)-induced liver fibrosis in rats and TGF-β1-treated HSC-T6 cells. Using ultrasonic imaging, H&E, Masson's, and Sirius Red staining, we demonstrated LF's ability to improve liver tissue damage and fibrosis induced by TAA. LF reduced the levels of ALT, AST, and hydroxyproline in TAA-treated liver tissues, while increasing catalase levels. Additionally, LF treatment decreased mRNA expression of inflammatory factors such as Il-1β and Icam-1 , as well as fibrogenic factors including α-Sma , Collagen I , and Ctgf in TAA-treated liver tissues. Furthermore, LF reduced TAA-induced ROS production and cell death in FL83B cells, and decreased α-SMA, Collagen I, and p-Smad2/3 productions in TGF-β1-treated HSC-T6 cells. Our study highlights LF's ability to ameliorate TAA-induced hepatocyte damage, oxidative stress, and liver fibrosis in rats, potentially through its inhibitory effect on HSC activation. These findings suggest LF's potential as a therapeutic agent for protecting against liver injuries and fibrosis. [Display omitted] • LF mitigates TAA-induced liver fibrosis via antioxidant and anti-inflammatory actions. • LF treatment reduces ALT, AST, and fibrosis markers in TAA-induced liver damage. • LF suppresses inflammatory and fibrogenic factors in TAA-treated liver tissues. • LF diminishes ROS production and cell death, offering hepatoprotective effects. • LF inhibits HSC activation, potentially serving as a therapeutic agent for liver fibrosis. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a progressive and life-threatening lung disease with high mortality rates. The limited availability of effective drugs for IPF treatment, coupled with concerns regarding adverse effects and restricted responsiveness, underscores the need for alternative approaches. Kefir peptides (KPs) have demonstrated antioxidative, anti-inflammatory, and antifibrotic properties, along with the capability to modulate gut microbiota. This study aims to investigate the impact of KPs on bleomycin-induced pulmonary fibrosis. Mice were treated with KPs for four days, followed by intratracheal injection of bleomycin for 21 days. Comprehensive assessments included pulmonary functional tests, micro-computed tomography (µ-CT), in vivo image analysis using MMPsense750, evaluation of inflammation- and fibrosis-related gene expression in lung tissue, and histopathological examinations. Furthermore, a detailed investigation of the gut microbiota community was performed using full-length 16 S rRNA sequencing in control mice, bleomycin-induced fibrotic mice, and KPs-pretreated fibrotic mice. In KPs-pretreated bleomycin-induced lung fibrotic mice, notable outcomes included the absence of significant bodyweight loss, enhanced pulmonary functions, restored lung tissue architecture, and diminished thickening of inter-alveolar septa, as elucidated by morphological and histopathological analyses. Concurrently, a reduction in the expression levels of oxidative biomarkers, inflammatory factors, and fibrotic indicators was observed. Moreover, 16 S rRNA sequencing demonstrated that KPs pretreatment induced alterations in the relative abundances of gut microbiota, notably affecting Barnesiella_intestinihominis , Kineothrix_alysoides , and Clostridium_viride. Kefir peptides exerted preventive effects, protecting mice against bleomycin-induced lung oxidative stress, inflammation, and fibrosis. These effects are likely linked to modifications in the gut microbiota community. The findings highlight the therapeutic potential of KPs in mitigating pulmonary fibrosis and advocate for additional exploration in clinical settings. • Idiopathic pulmonary fibrosis (IPF), a severe lung condition with high mortality, poses a significant health threat. • A murine model effectively mimics IPF symptoms three weeks post intratracheal bleomycin administration. • Kefir peptides (KPs) alleviate bleomycin-induced lung injury, improving respiratory function and reducing fibrosis. • KPs offer multifaceted defense, combating oxidative stress, inflammation, and profibrotic factors in pulmonary fibrosis. • KPs induce structural changes in the gut microbiota of bleomycin-induced pulmonary fibrotic mice. [ABSTRACT FROM AUTHOR]

This article reports our experience on the treatment of long-bone defects with double-strut vascular fibular graft in 11 patients. The defects were 6–12 cm in length while 10–25 cm of vascular fibular grafts were harvested. Nine patients achieved solid union in 6 months, and two patients required additional procedures to achieve solid union. No major complications were observed, except for three patients. who had knee stiffness due to long-term immobilization and one patient who had experienced a stress fracture because of strenuous exercise at 10 months after grafting procedures. Bone union in this patient was achieved 3 months after reapplying an external fixator.It is suggested that a rigid external or internal fixator is mandatory in the course of treatment for facilitating early knee mobilization to prevent exacerbation of already compromised knee-joint motion. Vigorous exercise should be avoided for at least 12 months after solid union of the graft to prevent graft fracture. We concluded that the double-strut vascular fibular graft is an effective treatment for complicated long-bone defects of lower extremity. [Copyright &y& Elsevier]

Depression is a prevalent, stress-related mental disorder that can lead to serious psychiatric diseases with morbidity and high mortality. Although some functional fermented dairy drinks have promising anxiolytic and antidepressant effects, the mechanism is still not clear. To determine the antidepressant-like effect and the potential molecule mechanism of kefir peptides (KP), various behavioral tests, including the elevated plus maze test, open field test, forced swimming test, and tail suspension test, were used. Administration of 150 mg/kg KP in mice reduced the duration of immobility in the forced swimming test and tail suspension test, elevated the time spent in the open arm and center zone in the elevated plus maze test, and increased the total distance traveled, average speed, and time spent in the center zone in the open field test compared with the mock group. These results indicated that KP dramatically ameliorated the depression-like behaviors. Kefir peptides were further isolated and identified using high-performance liquid chromatography and liquid chromatography–tandem mass spectrometry, from which 3 peptides were identified and designated KFP-1, KFP-3, and KFP-5. Among these peptides, administration of KFP-3 (15 AA residues) remarkably decreased immobility time in the forced swimming test and increased mobility time in the tail suspension test. Therefore, KFP-3 may be the major active peptide with antidepressant activity in KP. Overexpression of brain-derived neurotrophic factor, phosphorylated tropomyosin receptor kinase B, and phosphorylated ERK1/2 protein levels could be detected in the hippocampus under KP administration. Therefore, we suggest that KP improves depressive-like behaviors by activating the brain-derived neurotrophic factor–phosphorylated tropomyosin receptor kinase B signaling pathway. Kefir peptides may serve as a new type of antidepressant dairy product and may provide potent antidepressant effects for clinical use. [ABSTRACT FROM AUTHOR]

Akr1A1 is a glycolytic enzyme catalyzing the reduction of aldehyde to alcohol. This study aims to delineate the role of Akr1A1 in regulating the adipo-osteogenic lineage differentiation of mesenchymal stem cells (MSCs). MSCs derived from human bone marrow and Wharton Jelly together with gain- and loss-of-function analysis as well as supplementation with the S-Nitrosoglutathione reductase (GSNOR) inhibitor N6022 were used to study the function of Akr1A1 in controlling MSC lineage differentiation into osteoblasts and adipocytes. Akr1A1 expression, PKM2 activity, and lactate production were found to be decreased in osteoblast-committed MSCs, but PGC-1α increased to induce mitochondrial oxidative phosphorylation. Increased Akr1A1 inhibited the SIRT1-dependent pathway for decreasing the expressions of PGC-1α and TAZ but increasing PPAR γ in adipocyte-committed MSCs, hence promoting glycolysis in adipogenesis. In contrast, Akr1A1 expression, PKM2 activity and lactate production were all increased in adipocyte-differentiated cells with decreased PGC-1α for switching energy utilization to glycolytic metabolism. Reduced Akr1A1 expression in osteoblast-committed cells relieves its inhibition of SIRT1-mediated activation of PGC-1α and TAZ for facilitating osteogenesis and mitochondrial metabolism. Several metabolism-involved regulators including Akr1A1, SIRT1, PPARγ, PGC-1α and TAZ were differentially expressed in osteoblast- and adipocyte-committed MSCs. More importantly, Akr1A1 was identified as a new key regulator for controlling the MSC lineage commitment in favor of adipogenesis but detrimental to osteogenesis. Such information should be useful to develop perspective new therapeutic agents to reverse the adipo-osteogenic differentiation of BMSCs, in a way to increase in osteogenesis but decrease in adipogenesis. A graphical summary illustrates the hypothetical mechanism for Akr1A1 acting to determine MSC lineage differentiation into adipocytes (ADs) and osteoblasts (OBs). By using GSNOR inhibitor N6022, it is possible to alter the cell fate decision of BMSC toward OB differentiation. [Display omitted] • Akr1A1 is a master regulator in favor of adipogenesis but detrimental to osteogenesis. • OB-committed MSCs decreased Akr1A1, PKM2, and lactate production, but increased PGC-1α for mitochondrial metabolism. • AD-committed MSCs exhibited increases of Akr1A1, PKM2, and lactate production with decreased PGC-1α for glycolysis. • Akr1A1 inhibits the SIRT1-dependent pathway for decreasing PGC-1γ and TAZ, but increasing PPARγ in AD-committed MSCs. • Reduced Akr1A1 in OB-committed cells relieves inhibition on SIRT1-mediated activation of PGC-1γ and TAZ for osteogenesis. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The medicinal mushroom Antrodia cinnamomea has been used to treat cancer but its anti-angiogenic effects have not been studied in detail. Aim of the study The main objective of this study was to determine the molecular mechanism of activity underlying the anti-angiogenic effects of A. cinnamomea. Materials and methods The effects of an A. cinnamomea ethanol extract (ACEE) on cell migration and microvessel formation were investigated in endothelial cells in vitro and Matrigel plugs implanted into mice in vivo . Activation of intracellular signaling pathways was examined using Western blotting. Protein expression was assessed using immunohistochemistry in a mouse model of lung metastasis. Results We show that treatment with ACEE inhibits cell migration and tube formation in human umbilical vein endothelial cells (HUVECs). ACEE suppresses phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) and expression of pro-angiogenic kinases in vascular endothelial growth factor (VEGF)-treated HUVECs, in addition to reducing expression of Janus kinase 2 (JAK2) and phosphorylation of signal transducer and activator of transcription 3 (STAT3). ACEE treatment inhibits VEGF-induced microvessel formation in Matrigel plugs in vivo . In addition, ACEE significantly reduces VEGFR2 expression in Lewis lung carcinoma cells and downregulates the expression of cluster of differentiation 31 (CD31) and VEGFR2 in murine lung metastases. Conclusion These results indicate that A. cinnamomea produces anti-angiogenic effects by inhibiting the VEGFR2 signaling pathway. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune disease. Its pathological features are synovial inflammation, bone erosion, and joint structural damages. Our previous studies have shown that kefir peptides (KPs) can reduce cardiovascular disease, osteoporosis and renal inflammation. In this study, we further evaluate the efficacy of KPs on adjuvant-induced arthritis (AIA) in a rat model. After the 14th day of adjuvant induction, rats were subsequently orally administered KPs (83 or 166 mg/day/kg) or tofacitinib (6.2 mg/day/kg) for 14 days. On the 28th day, the rats were anesthetized with isoflurane for ultrasonic, in vivo imaging system (IVIS), and radiographic imaging and then sacrificed for ankle tissues collection and analysis. In vitro , IL-1β-treated human synovial cells (SW982) were subjected to anti-arthritis mechanism study in the presence of KPs. The results of ultrasonography, radiograph, histology, the expression of matrix metalloproteinases (MMPs), inflammatory cytokines and RANKL/OPG ratio demonstrated decreasing severity of synovitis and bone erosion in the ankle joints after KPs treatment. Activation of the NF-κB and MAPK pathways was significantly reduced in KPs treated AIA group. Furthermore, KPs attenuated IL-1β-induced inflammatory cytokine production and the expression of MMPs in a human synovial cell line SW982. These results demonstrated that KPs alleviated adjuvant-induced arthritis in rats by inhibiting IL-1β-related inflammation and MMPs production. We concluded that KPs can exhibit anti-inflammatory effects by reducing the levels of macrophage-related inflammatory cytokines and MMPs, thus alleviating bone erosion in the ankle joint and constituting a potential therapeutic strategy for rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Transgenic animals are important in vivo models for biological research. However, low transgenic rates are commonly reported in the literature. Lentiviral transgenesis is a promising method that has greater efficiency with regard to generating transgenic animals, although the transgenic rate of this approach is highly dependent on different transgenes and concentrated lentiviruses. In this study, we modified a method to concentrate lentiviruses using a table centrifuge, commonly available in most laboratories, and carried out analysis of the transgenic efficiency in mice. Based on 26 individual constructs and 627 live pups, we found that the overall transgenic rate was more than 30%, which is higher than obtained with pronuclear microinjection. In addition, we did not find any significant differences in transgenic efficiency when the size of inserts was less than 5000 bp. These results not only show that our modified method can successfully generate transgenic mice but also suggest that this approach could be generally applied to different constructs when the size of inserts is less than 5000 bp. It is anticipated that the results of this study can help encourage the wider laboratory use of lentiviral transgenesis in mice. [ABSTRACT FROM AUTHOR]

Fractures are the result of fragile bone structures after trauma caused by direct or indirect external impact or strong muscular contraction. Most fracture patients undergo surgical fixation to accelerate the healing process and restore the function of mutilated bone. Promoting the healing process remains an important issue for the treatment of bone fractures. Our previous studies demonstrated the remarkable bone-protective effects of kefir peptides (KPs) in ovariectomized rats and mice. In this study, we further evaluate the efficacy of KPs on fracture healing using a rat model of femoral fracture. Fifteen 8-week-old male Sprague Dawley (SD) rats were divided into the sham, mock, and KPs groups, in which the mock and the KPs groups underwent femur-fracture surgery with nail fixation, while the sham group underwent a sham operation. The next day, rats were orally administered with daily 400 mg/kg of KPs (KPs group) or distilled water (sham and mock groups) for four weeks. X-ray imaging, histochemical staining and serum osteogenic markers were applied for fracture healing evaluation. In vitro, mouse bone marrow mesenchymal stem cells (BMMSCs) and MC3T3-E1 line were subjected to osteoblast differentiation in the presence of KPs and compared with no KPs treatment. The results demonstrated that KPs treatment improved the progression of the fracture healing process (p < 0.05) and significantly increased the expressions of Col1a1, Alp, Spp1 , Vegfa and Cox2 mRNA in the femurs of the KPs-treated fractured rats compared to those of the mock-treated fracture rats. In vitro, KPs treatment promoted bone regeneration factor (Col1a1, Alp, M-csf and Phospho1) expression in MC3T3-E1-derived osteoblast cultures (on Day 3) and enhanced osteogenic differentiation and mineralization in BMMSC-derived osteoblast cultures (on Day 17 and Day 21). This is the first study to show that KPs can help with fracture healing by promoting osteogenic differentiation, and it also suggests that KPs can be used as a nutritional supplement to accelerate fracture healing. [ABSTRACT FROM AUTHOR]

The AKR1A1 protein is a member of the aldo-keto reductase superfamily that catalyzes the transformation of D -glucuronate to L -gulonate in the synthesis of L -ascorbic acid (vitamin C, Vit C). We previously demonstrated that AKR1A1 knockout mice (AKR1A1 eGFP/eGFP ) with Vit C deficiency exhibited aberrant bone formation and osteoporosis. In this study, we aimed to evaluate the osteoprotective effects of kefir peptides (KPs) in AKR1A1 eGFP/eGFP mice and uncover the underlying mechanism of KPs in the modulation of bone remodeling. Six male CD-1 mice and 24 male AKR1A1 eGFP/eGFP mice were used in this study, in which the AKR1A1 eGFP/eGFP mice were randomly divided into four groups (n = 6). KPs treatment for 12 weeks exerted several effects in AKR1A1 eGFP/eGFP mice including the reduction of serum proinflammatory cytokines (IL-1β, IL-6, TNF-α), bone resorption markers (CTX-1, RANKL), and the increase of serum bone formation markers (P1NP, OPG, OC). μ-CT analysis indicated that KPs prevented the bone loss in the femurs of AKR1A1 eGFP/eGFP mice by significantly increasing the trabecular parameters of bone mineral density, bone volume and bone number. Nanoindentation analysis demonstrated that KPs enhanced the elasticity and hardness of femoral cortical bones in AKR1A1 eGFP/eGFP mice. KPs promoted bone marrow mesenchymal stem cells (BMMSCs)-derived osteoblast differentiation and mineralization by upregulating positive regulators of osteoblastogenesis (Runx2, β-catenin, BMP-2, NFATc1). Conversely, KPs inhibited bone marrow macrophages (BMMs)-derived osteoclast differentiation and bone resorption, which was demonstrated by the facts that KPs suppressed RANKL-induced p38, NF-κB, Akt, PLCγ2 and CREB-1 phosphorylation, decreased the nuclear translocation of NFATc1 and c-Fos. Our findings demonstrate the efficacy of KPs in the prevention of osteoporosis in AKR1A1 eGFP/eGFP mice and also unveil the dual effects of KPs in osteogenic promotion and osteoclastic inhibition. This study supports the use of KPs as nutritional supplements for the prevention of osteoporosis. [Display omitted] • AKR1A1 KO mice with Vit C deficiency developed the osteoporotic phenotypes. • Kefir peptides (KPs) prevent the development of osteoporosis in AKR1A1 KO mice with Vit C deficiency. • KPs inhibit in vitro RANKL-induced osteoclastogenesis. • KPs enhance in vitro osteoblastogenesis. • KPs modulate the bone remodeling in favor of bone formation. [ABSTRACT FROM AUTHOR]

Aim Muscle atrophy is a common symptom after nerve denervation. Myostatin propeptide, a precursor of myostatin, has been documented to improve muscle growth. However, the mechanism underlying the muscle atrophy attenuation effects of myostatin propeptide in muscles and the changes in gene expression are not well established. We investigated the possible underlying mechanisms associated with myostatin propeptide gene delivery by gene gun in a rat denervation muscle atrophy model, and evaluated gene expression patterns. Main methods In a rat botulinum toxin-induced nerve denervation muscle atrophy model, we evaluated the effects of wild-type (MSPP) and mutant-type (MSPPD75A) of myostatin propeptide gene delivery, and observed changes in gene activation associated with the neuromuscular junction, muscle and nerve. Key findings Muscle mass and muscle fiber size was moderately increased in myostatin propeptide treated muscles ( p < 0.05). And enhancement of the gene expression of the muscle regulatory factors, neurite outgrowth factors (IGF-1, GAP43) and acetylcholine receptors was observed. Our results demonstrate that myostatin propeptide gene delivery, especially the mutant-type of MSPPD75A, attenuates muscle atrophy through myogenic regulatory factors and acetylcholine receptor regulation. Significance Our data concluded that myostatin propeptide gene therapy may be a promising treatment for nerve denervation induced muscle atrophy. [ABSTRACT FROM AUTHOR]

Aim Diabetic nephropathy is the leading cause of end stage renal disease in developed countries throughout the world. The imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense system is the main problem that is responsible for the progression of diabetic kidney disease. In this study, we investigated whether human extracellular superoxide dismutase (hEC-SOD) can prevent diabetic nephropathy in the rat model. Main methods Diabetic nephropathy symptoms were induced by intraperitoneal injection with 60 mg/kg streptozotocin (STZ) in male Sprague–Dawley (SD) rats. After daily supplement of rhEC-SOD (3200 U/kg/day) for 4 weeks, the serum or urine biochemical markers (glucose, creatinine, blood urea nitrogen, triglyceride, hemoglobin A1c, and microalbuminuria), histological changes, gene expressions ( phox47 , opn , and gapdh ), and protein levels (TGF-β, AT1-R, phospho-p42/p44 MAPK, and p42/p44 MAPK) were determined. Key findings Results showed that rhEC-SOD administration could reverse SOD activity measured in kidney and diabetic-associated changes, including the fibrosis change, expression of collagen I, transforming growth factor-beta (TGF-β) and angiotensin II type I receptor (AT1-R), as well as the activation of the intracellular mitogen-activated protein kinase (MAPK) signaling pathway, associating with its inhibition of p42 MAPK /p44 MAPK (ERK1/2) phosphorylation. Additionally, diabetic nephropathy up-regulated the expression of the phox47 and opn genes, and these changes could also be suppressed. Though the proteinuria did not significantly reduce. Treatment with rhEC-SOD ameliorates STZ-induced diabetic nephropathy, leading to reduced death rates, kidney weight/body weight ratio, fibrosis change, and TGF-β1 expression through the down-regulation of ROS/ERK1/2 signaling pathway. Significance We conclude that rhEC-SOD can act as a therapeutic agent to protect the progression of diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Ethnopharmacological evidence Antrodia camphorata , a highly valued polypore mushroom native only to Taiwan, has been traditionally used as a medicine for anti-inflammation. Aim of the study In this study, anti-inflammatory effects of Antrodia camphorata (AC) and its active compound, ergostatrien-3β-ol (ST1), were investigated in a mouse skin ischemia model induced by skin flap surgery on the dorsal skin. Materials and methods A U-shaped flap was elevated on the dorsal skin of the nine-week-old male mice. Mice were randomly assigned to six groups for treatment ( n =6) including normal skin/propylene glycol (PG), surgical skin flap/PG, solid-state-cultured AC (S/AC), wood-cultured AC (W/AC), high-dose ST1 (H-ST1), low-dose ST1 (L-ST1). Antrodia camphorata was dissolved in 25 μL PG and smeared on the skin flap every six hours for 24 h. At the end of the experiment, each mouse was anesthetized, and skin tissues were collected from their back for histopathological analysis, extracting RNA and protein according to our previous reports. Results Skin-flap-induced ischemia damage significantly increased the expression of the iNOS, COX2, and IL-6 proteins and decreased the expression of IκB protein. In addition, focal, moderate coagulative necrosis with inflammatory cell infiltration was found in the epidermis, and moderate inflammatory cells and necrosis with slight edema was noted in the sub-dermis at 24 h after skin flap surgery. However, treatment with solid-state-cultured or wood-cultured AC, or with its derived ST1 active compound, significantly reduced the necrosis and inflammatory cell infiltration in both the epidermis and sub-dermis of the skin flap. The treatments also reduced the inflammatory response by decreasing the expression of inflammation-related genes including iNOS, IL-6, TNF-α, and NF-κB, as shown by changes in RNA and protein expression, when compared with the surgical skin flap procedure alone. Conclusions These results demonstrated that methanolic extracts of wood-cultured fruiting bodies and solid-state-cultured mycelia from Antrodia camphorata have excellent anti-inflammatory activities and thus have great potential as an addition for hydrocolloid dressings. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The molecular mechanisms underlying stress urinary incontinence (SUI) are not clear. In light of the limited availability of human tissue for study, we explored the changes in the urethra of C57BL/6 mice with experimentally induced SUI. Study design: Twelve virgin female mice were randomized into two groups: one group undergoing vaginal distension (VD) for 1h with an 8-mm dilator, and a non-instrumented control group. Four days after VD, leak point pressures (LPP) and maximum urethral closure pressure (MUCP) were assessed in these mice under urethane (1g/kg, i.p.) anesthesia. After measuring LPP and MUCP, the animals were sacrificed, and the urethras were removed for proteomic analysis using 2-dimensional differential gel electrophoresis (2D DIGE) and liquid chromatography–tandem mass spectrometry (LC–MS/MS) technology. Lastly, interaction between these proteins was further analyzed using MetaCore. Results: LPP and MUCP values were significantly decreased in the 8-mm VD groups compared with the non-instrumented control group. Sixty-eight differentially expressed proteins of urethra from female mice with and without VD were identified. Of these, 19 proteins were up-regulated and 49 were down-regulated. The majority of the VD-induced proteins were involved in generation of precursor metabolites and energy, oxidation of reduction, regulation of apoptosis, and glycolysis. Myosin expression in the urethra was significantly decreased in the 8-mm VD group as compared with the control group. Conclusions: As a model of simulated birth trauma, VD can induce SUI in female mice. Under-expression of myosin plays a plausible role in the pathogenesis of SUI following vaginal trauma. [Copyright &y& Elsevier]

Abstract: Objective: To investigate whether adenotonsillectomy reduces upper respiratory tract infections (URIs) in the pediatric population. Methods and subjects: We identified 415 children, aged ≤18 years who had undergone adenoidectomy and/or tonsillectomy during the period from 1999 to 2006, from the Taiwan National Health Insurance Research Database. The comparison group consisted of 1630 children without the surgery randomly selected from the same database frequency matched with sex, age and the surgery date (index date). Changes in physician visits for URIs 2-year period before and 2-year period after the index date were compared between the two groups of children. Results: The number of outpatient visits for URIs decreased with time, children with tonsillectomy and/or adenoidectomy had a greater reduction than comparison children (mean changes, −14 times and −6 times, respectively) in the 2-year period after the index date. Multivariate analyses using generalized estimated equation revealed a significant effect in reducing URIs visits from the surgery (relative ratio=0.85, p <0.0001), strongest for children undergoing both tonsillectomy and adenoidectomy (relative ratio=0.76, p <0.0001). The association between surgery and the decrease in URIs was more pronounced for children aged 12 years and less. Conclusion: This population-based study suggests that tonsillectomy and/or adenoidectomy is associated with fewer physician visits for URIs. The association is weakened in old children. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological evidence: Gexia-Zhuyu Tang (GZT), also called Gexiazhuyu decoction (GXZYD), is a traditional Chinese herbal medicine for chronic liver diseases such as cirrhosis and liver fibrosis. Aim of the study: In this study, we have investigated the affects of GZT on a rat model of dimethylnitrosamine (DMN)-induced liver fibrosis. Materials and methods: In this study, the protective effects of GZT on DMN-induced liver fibrosis were measured using a rat model. Following 5weeks of DMN-treatment (8mg/kg, i.p., given 3 consecutive days each week), oral administration of GZT at 1.8g/kg daily via oral gavage for 2weeks beginning at week 13. Results: Both body and liver weights were significantly decreased. The reductions in body and liver weights corresponded with increasing liver damage severity. Furthermore, GZT-treatment remarkably decreased the levels of serum GOT (glutamate oxaloacetate transaminase) and GPT (glutamic pyruvic transaminase), and the mRNA expression levels of collagen alpha-1(I) and alpha-smooth muscle actin (alpha-SMA) in DMN-induced hepatic fibrosis. In addition, hepatic stellate cells (HSCs) play a major role in various types of liver fibrosis through initial myofibroblast transformation. The proliferation of HSCs was inhibited by GZT. Treatment with GZT also induced HSC apoptosis in a dose- and time-dependent manner. GZT treatment induced HSC apoptosis by facilitating Ca2+ release from the mitochondria within 6h. Subsequently, caspases 3 and 12 were elevated by 72h after treatment. Conclusions: Our studies indicate that GZT exhibited both hepatoprotective and antifibrogenic effects in DMN-induced hepatic injury. These findings suggest that GZT may be useful in preventing the development of hepatic fibrosis. [Copyright &y& Elsevier]

Abstract: Aims of the study: Yi Guan Jian (YGJ) has long been employed clinically to treat liver fibrosis in traditional Chinese Medicine but the mechanism underlying the regulation has not been clarified in detail. The present investigation was designed to assess the involvement of the fibrosis pathway in dimethylnitrosamine (DMN)-induced liver fibrosis in rats. Materials and methods: Liver fibrosis was induced by DMN injection (10mg/kg, i.p., given three consecutive days each week) following 4weeks. YGJ was oral administered (1.8g/kg daily via gastrogavage for two weeks). Liver sample were subjected to histological and western blot studies. For evaluation of hepatic fibrosis-related factors, collagen α1-I, tissue inhibitor of metalloproteinase-1 (TIMP-1), and α-smooth muscle actin (α-SMA) mRNA and protein levels were analyzed. Results: YGJ remarkably prevented body weight loss and DMN damage in the liver, and it inhibited the elevation of serum glutamate oxaloacetate transaminase (GOT), and glutamic pyruvic transaminase (GPT). Oral administration of YGJ extract significantly reduced the accumulation of collagen α1-I, TIMP-1, and α-SMA in liver tissues. Conclusions: Taken together, these findings indicate that the YGJ Chinese herb showed hepatoprotective and anti-fibrogenic effects against DMN-induced hepatic injury. Our data suggest that the YGJ may be useful in reversing the development of hepatic fibrosis. [Copyright &y& Elsevier]

Abstract: The purpose of this study was to investigate the effects of dietary supplementation with recombinant porcine lactoferrin (rPLF) produced by yeast culture on peripheral lymphocyte proliferation and serum antibody titers in chickens vaccinated against the infectious bursal disease (IBD) virus. Treatment groups were fed with rPLF powder in their diet (2.0%, w/w), and the IBD vaccine was administrated at 1 and 3 weeks of age. At 8, 12, and 16 weeks after vaccination, serum IBD antibody titers were measured via the micro-method and T cell proliferation rates were evaluated. In gene expression analyses, rPLF-treated chicken peripheral T lymphocytes were stimulated with concanavalin A (ConA) for 24h. The mRNA expression levels of interleukin-2 (IL-2), interferon-γ (IFN-γ), interleukin-4 (IL-4), and interleukin-12 (IL-12) were determined using a semi-quantitative RT-PCR assay. The results revealed that the rPLF additive led to significant increases in serum IgG and IBD-specific antibody titers (P <0.05). The rPLF administration significantly increased chicken intestinal villous lengths and also enhanced the expression of IFN-γ and IL-12 in chicken T lymphocytes. These data suggest that rPLF enhances cell-mediated immunity and augment the ability of IBD vaccination to benefit chicken industry in disease resistance. [Copyright &y& Elsevier]

Abstract: Enterovirus 71 (EV71) is the most common etiological agent detected in cases of hand-foot-and-mouth disease (HFMD) resulting in incidences of neurological complications and fatality in recent years. The clinical data have already shown the significant increase in recent EV71 epidemic activity throughout the Asia-Pacific region. Due to the lack of an effective antiviral agent, primary prevention of the disease, including the development of an effective vaccine, has been the top priority in terms of control strategies. In this study, we first generated a transgenic animal system to produce the EV71 VP1 capsid protein under the control of α-lactalbumin promoter and α-casein leader sequences. A high level of recombinant VP1 protein (2.51mg/ml) was expressed and secreted into the milk of transgenic mice. Mouse pups that received VP1-transgenic milk orally demonstrated relatively better health conditions after challenge with the respective virus as compared with the non-transgenic milk fed group; moreover, the mice fed with the VP1-milk had body weights similar to those of the PBS placebo control groups. According to the serum-neutralization assay and serum antibody detection, the littermates suckling VP1-milk generated antibodies specific to EV71. Our data suggest that EV71 VP1-containing milk is suitable for development as a potential oral vaccine. [Copyright &y& Elsevier]

Summary: The human Enterovirus genus of the piconavirus family causes most of the febrile illnesses that affect children during the summer season in Taiwan. Enterovirus type 71 (EV71) plays a key role in patients with hand-foot-and-mouth disease (HFMD) combined with severe paralysis or encephalitis. It is important to find a method for preventing infection with EV71 since there is no antiviral agent or vaccine for humans. In this study, we developed a transgenic mouse model for demonstrating the protective effects of recombinant lactoferrin (LF) against EV71 infection. Transgenic mice carrying alpha-lactalbumin-porcine lactoferrin (αLA-pLF) and BALB/c wild-type mice were subjected to EV71 inoculation. First, we analyzed the expression efficiencies of recombinant pLF (rpLF) in hemizygous and homozygous transgenic mice. Following EV71 inoculation on the 4th day of life, pups ingesting transgenic milk showed the significantly higher survival rate and heavier body weight compared to wild-type mice. RT-PCR analysis for EV71 viral RNA showed that the recombinant pLF had a blocking effect on EV71 infection. Our data suggest that oral intake of pLF-enriched milk exhibited the ability to prevent infection with EV71. The study also provides an animal model for validating the protective effects of pLF. [Copyright &y& Elsevier]

Summary: From January 1993 to September 2002, 931 patients suffered from intertrochanteric fracture and subrochanteric fracture received open reduction and internal fixation with APGN in our institute. Among these patients, 16 patients (1.7%) developed a femoral shaft fracture after the initial fixation with APGN. Removal of the APGN, closed reduction and fixation with long Gamma nail (LGN) was performed in all the 16 patients. The patients were followed for 12–60 months (average, 39.8 months). The union time of fracture was 12–24 weeks (average, 18.5 weeks) for femoral shaft fractures and 12–20 weeks (average, 16 weeks) for peritrochanteric fractures. Two early complications were noted, including one superficial (6%) infection and one deep (6%) infection. Two malunions (12.5%) developed with no definite functional impairment. The functional results using the Harris hip score were good to excellent. In conclusion, closed reduction and internal fixation with a LGN is very effective in the management of a femoral shaft fracture, a complication of a previous APGN that had been initially used for stabilisation of a pertrochanteric fracture. [Copyright &y& Elsevier]

Huntington's disease (HD) is a neurodegenerative disease that causes deficits in neurite outgrowth, which suggests that enhancement of neurite outgrowth is a potential direction by which to improve HD. Our previous publications showed that fibroblast growth factor 9 (FGF9) provides anti-apoptosis and anti-oxidative functions in striatal cell models of HD through the extracellular signal–regulated kinases (ERK) pathway, and FGF9 also stimulates cytoskeletons to enhance neurite outgrowth via nuclear factor kappa B (NF-kB) signaling. In this study, we further demonstrate the importance of the ERK pathway for the neurite outgrowth induced by FGF9 in HD striatal models. FGF9 was treated with ERK (U0126) or NF-kB (BAY11-7082) inhibitors in STHdhQ7/Q7 and STHdhQ111/Q111 striatal knock-in cell lines to examine neurite outgrowth, cytoskeletal markers, and synaptic proteins via immunofluorescence staining and Western blotting. NF-kB activity was analyzed by NF-kB promoter reporter assay. Here, we show that suppression of ERK signaling significantly inhibits FGF9-induced neurite outgrowth, cytoskeletal markers, and synaptic proteins in HD striatal cells. In addition, we also show suppression of ERK signaling significantly decreases FGF9-induced NF-kB activation, whereas suppression of NF-kB does not decrease FGF9-induced ERK signaling. These results suggest that FGF9 activates ERK signaling first, stimulates NF-kB upregulation, and then enhances neurite outgrowth in HD striatal cells. We elucidate the more detailed mechanisms of neurite outgrowth enhanced by FGF9 in these HD striatal cells. This study may provide insights into targeting neurite outgrowth for HD therapy. Unlabelled Image [ABSTRACT FROM AUTHOR]