Cardiac-to-Bronchial Fistula in Hepatocellular Carcinoma: A Case Report.

Hepatocellular carcinoma (HCC) stands as a significant contributor to cancer-related mortality globally. While the acute and often fatal manifestations of locally advanced HCC primarily present within the abdomen, it is crucial to recognize that the respiratory and circulatory systems can also fall victim due to the liver's unique anatomical position within the body. Here, we present the case of a 63-year-old male recently diagnosed with locally advanced HCC with vascular invasion. Shortly after receiving target therapy and focal radiotherapy, the patient developed repeated secondary infections and a persistent diaphragmatic defect. As the necrotic tissue invaded the pleural space, subsequent tumor-to-bronchial and tumor-to-cardiac fistulas emerged, resulting in an abnormal connection between the respiratory and cardiovascular systems, leading to massive air emboli in circulation. This report highlights the risk of supradiaphragmatic complications in HCC patients with post-treatment secondary infections, particularly in patients predisposed to developing diaphragmatic defects.

Bidirectional associations between hyperopia, myopia, astigmatism, and strabismus, and attention-deficit/hyperactivity disorder in children: a national population-based cohort study

Objectives: The present study analyzed the reciprocal relationships between four common pediatric ophthalmic diseases (i.e., hyperopia, myopia, astigmatism, and strabismus) and attention‐deficit/hyperactivity disorder (ADHD) in children. Methods: This study enrolled 86,028 children with ADHD and 1,798,673 children without ADHD in the Taiwan Maternal and Child Health Database who were born at any time from 2004 to 2017. Cox proportional hazards regression models were used to estimate the bidirectional relationships of the four ophthalmic diseases with ADHD in children after adjusting for age, sex, and gestational age at birth. Survival curves for time-to-event variables were estimated using the Kaplan-Meier method, and the log-rank test was used to compare the curves. Results: The results indicated that ADHD significantly predicted the occurrence of hyperopia, myopia, astigmatism, and strabismus. Furthermore, hyperopia, myopia, astigmatism, and strabismus significantly predicted the occurrence of ADHD. The time between enrollment and ADHD diagnosis was shorter for patients with ophthalmic diseases than for the control group, and the time between enrollment and ophthalmic disease diagnosis was also shorter for ADHD patients than for the control group. Sex differences were found in the associations between ADHD and ophthalmic diseases. Conclusion: Clinicians should monitor children with ADHD for hyperopia, myopia, astigmatism, and strabismus to ensure appropriate treatment, and vice versa.

Efforts to improve the surgical outcome for exotropia and investigation of the insertion locations of the extraocular muscles.

In our previous retrospective study, we found that using the strabismus surgery dosages established by western strabismus mentors tends to result in undercorrection of Taiwanese exotropia (XT) patients compared with those in western populations. We also discovered that the location of extraocular muscle (EOM) insertion could vary by ethnicity. In this study, using a generalized estimation equation model, we compared the XT surgery outcome between augmented and original strabismus surgery dosages in Taiwanese patients. We also conducted an observational study to investigate the horizontal EOM insertion location in a Taiwanese population and compared the data with Dr. Apt L.'s study. For Taiwanese XT patients, augmented surgical dosages resulted in significantly better outcome at 6 months and 1 year postoperatively compared with original surgical dosages (p = 0.003 and p < 0.001, respectively). The distance from the lateral recuts muscle (LR) insertion location to the limbus was significantly shorter in Taiwanese than in white Americans (6.5 vs. 6.9 mm, respectively, p = 0.0001). Furthermore, the medial rectus muscle and LR insertion locations differed significantly between males and females (p < 0.001 and p = 0.023, respectively). The patients' sex did not affect the surgery outcome. Augmented surgery doses modified from western strabismus mentors produce better surgery outcome for Taiwanese XT patients. Surgeons may require country-specific guidelines for strabismus surgery dosage. We also demonstrated a simple method for young ophthalmologists to establish their own normograms to improve their surgical success rate. Our study confirms that LR insertion locations differ between Taiwanese and White Americans.

Nordalbergin Exerts Anti-Neuroinflammatory Effects by Attenuating MAPK Signaling Pathway, NLRP3 Inflammasome Activation and ROS Production in LPS-Stimulated BV2 Microglia.

Microglia-associated neuroinflammation is recognized as a critical factor in the pathogenesis of neurodegenerative diseases; however, there is no effective treatment for the blockage of neurodegenerative disease progression. In this study, the effect of nordalbergin, a coumarin isolated from the wood bark of Dalbergia sissoo, on lipopolysaccharide (LPS)-induced inflammatory responses was investigated using murine microglial BV2 cells. Cell viability was assessed using the MTT assay, whereas nitric oxide (NO) production was analyzed using the Griess reagent. Secretion of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) was detected by the ELISA. The expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, mitogen-activated protein kinases (MAPKs) and NLRP3 inflammasome-related proteins was assessed by Western blot. The production of mitochondrial reactive oxygen species (ROS) and intracellular ROS was detected using flow cytometry. Our experimental results indicated that nordalbergin ≤20 µM suppressed NO, IL-6, TNF-α and IL-1ß production; decreased iNOS and COX-2 expression; inhibited MAPKs activation; attenuated NLRP3 inflammasome activation; and reduced both intracellular and mitochondrial ROS production by LPS-stimulated BV2 cells in a dose-dependent manner. These results demonstrate that nordalbergin exhibits anti-inflammatory and anti-oxidative activities through inhibiting MAPK signaling pathway, NLRP3 inflammasome activation and ROS production, suggesting that nordalbergin might have the potential to inhibit neurodegenerative disease progression.

Magnolol regulates miR-200c-3p to inhibit epithelial-mesenchymal transition and retinoblastoma progression by modulating the ZEB1/E-cadherin axis in vitro and in vivo.

BACKGROUND: Retinoblastoma, the most common pediatric intraocular malignancy, can develop during embryogenesis, with most children being diagnosed at 3-4 years of age. Multimodal therapies are typically associated with high levels of cytotoxicity and side effects. Therefore, the development of novel treatments with minimal side effects is crucial. Magnolol has a significant anti-tumor effect on various cancers. However, its antitumor effect on retinoblastoma remains unclear. PURPOSE: The study aimed to determine the effects of magnolol on the regulation of EMT, migration, invasion, and cancer progression in retinoblastoma and the modulation of miR-200c-3p expression and the Wnt/ zinc finger E-box binding homeobox 1 (ZEB1)/E-cadherin axis in vivo and in vitro. METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay was used to evaluate magnolol-induced cell toxicity in the Y79 retinoblastoma cell line. Flow cytometry and immunostaining assays were performed to investigate the magnolol-regulated mitochondrial membrane potential and the intracellular and mitochondrial reactive oxygen species levels in Y79 retinoblastoma cells. Orthotopic and subcutaneous xenograft experiments were performed in eight-week-old male null mice to study retinoblastoma progression and metastasis. In situ hybridization and quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays were performed to evaluate the level of the anti-cancer miRNA miR-200c-3p. The mRNA and protein levels of E-cadherin, ß-catenin, α-smooth muscle actin (α-SMA), fibronectin-1, and ZEB1 were analyzed using RT-qPCR, immunoblot, immunocytochemistry, and immunohistochemistry assays in vitro and in vivo. RESULTS: Magnolol increased E-cadherin levels and reduced the activation of the EMT signaling pathway, EMT, tumor growth, metastasis, and cancer progression in the Y79 retinoblastoma cell line as well as in the orthotopic and subcutaneous xenograft animal models. Furthermore, magnolol increased the expression of miR-200c-3p. Our results demonstrate that miRNA-200c-3p inhibits EMT progression through the Wnt16/ß-catenin/ZEB1/E-cadherin axis, and the ZEB1 silencing response shows that miR-200c-3p regulates ZEB1-mediated EMT in retinoblastoma. CONCLUSION: Magnolol has an antitumor effect by increasing E-cadherin and miRNA-200c-3p expression to regulate ZEB1-mediated EMT and cancer progression in retinoblastoma. The anti-tumor effect of magnolol by increasing E-cadherin and miRNA-200c-3p expression to regulate ZEB1-mediated EMT and cancer progression in retinoblastoma has been elucidated for the first time.

Mycotoxin Zearalenone Attenuates Innate Immune Responses and Suppresses NLRP3 Inflammasome Activation in LPS-Activated Macrophages.

Zearalenone (ZEA) is a mycotoxin that has several adverse effects on most mammalian species. However, the effects of ZEA on macrophage-mediated innate immunity during infection have not been examined. In the present study, bacterial lipopolysaccharides (LPS) were used to induce the activation of macrophages and evaluate the effects of ZEA on the inflammatory responses and inflammation-associated signaling pathways. The experimental results indicated that ZEA suppressed LPS-activated inflammatory responses by macrophages including attenuating the production of proinflammatory mediators (nitric oxide (NO) and prostaglandin E2 (PGE2)), decreased the secretion of proinflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6), inhibited the activation of c-Jun amino-terminal kinase (JNK), p38 and nuclear factor-κB (NF-κB) signaling pathways, and repressed the nucleotide-binding and oligomerization domain (NOD)-, leucine-rich repeat (LRR)- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. These results indicated that mycotoxin ZEA attenuates macrophage-mediated innate immunity upon LPS stimulation, suggesting that the intake of mycotoxin ZEA-contaminated food might result in decreasing innate immunity, which has a higher risk of adverse effects during infection.

Thrombospondin 1-induced exosomal proteins attenuate hypoxia-induced paraptosis in corneal epithelial cells and promote wound healing.

Thrombospondin-1 (TSP1) is involved in corneal wound healing caused by chemical injury. Herein, we examined the effects of TSP1 on hypoxia-induced damages and wound-healing activity in human corneal epithelial (HCE) cells. Exosomal protein expression was determined using liquid chromatography-tandem mass spectrometry, and HCE cell migration and motility were examined through wound-healing assay and time-lapse microscopy. Reestablishment of cell junctions by TSP1 was assessed through confocal microscopy and 3D image reconstruction. Our results show that CoCl2 -induced hypoxia promoted HCE cell death by paraptosis. TSP1 protected these cells against paraptosis by attenuating mitochondrial membrane potential depletion, swelling and dilation of endoplasmic reticulum and mitochondria, and mitochondrial fission. Exosomes isolated from HCE cells treated with TSP1 contained wound healing-associated proteins that were taken up by HCE cells to promote tissue remodeling and repair. TSP1 protected HCE cells against hypoxia-induced damages and inhibited paraptosis progression by promoting cell migration, cell-cell adhesion, and extracellular matrix remodeling. These findings indicate that TSP1 ameliorates hypoxia-induced paraptosis in HCE cells and promotes wound healing and remodeling by regulating exosomal protein expression. TSP1 may, therefore, play important roles in the treatment of hypoxia-associated corneal diseases.

Hypoxia-induced vascular endothelial growth factor secretion by retinal pigment epithelial cells is inhibited by melatonin via decreased accumulation of hypoxia-inducible factors-1α protein.

BACKGROUND: Hypoxia is the most important stimulus leading to up-regulation of vascular endothelial growth factor (VEGF) in the retina via elevation of hypoxia-inducible factors-1α (HIF-1α) protein. The purpose of this study was to test the effects of melatonin on the expression of VEGF and HIF-1α in the cultured human retinal pigment epithelial (RPE) cells under normoxia and hypoxia. METHOD: An in vitro RPE cell hypoxia model was established by placing cells under 1% oxygen pressure or by adding cobalt chloride (CoCl2 ) to the culture medium. RPE cells and conditioned media were collected from cultures treated with and without melatonin under normoxia and hypoxia. The protein and RNA levels of VEGF and HIF-1α were measured by ELISA kits and RT-PCR, respectively. RESULT: Hypoxia induced a significant increase of expression and secretion of VEGF and accumulation of HIF-1α protein in RPE cells (P < 0.05). Melatonin at 10-5 to 10-8 M significantly inhibited hypoxia-induced expression, the secretion of VEGF and the accumulation of HIF-1α protein (P < 0.05), but not affected expression of VEGF and HIF-1α under normoxia (P > 0.05). CONCLUSION: This study suggests that melatonin may have potential value in the prevention and treatment of various retinal diseases associated with increase of VEGF, vascular leakage and angiogenesis.

Intraretinal cystoid spaces in a patient with retinitis pigmentosa due to mutation in the MAK gene.

BACKGROUND: Cystoid macular edema (CME) and non-leaking intraretinal cystoid spaces (ICS) have different pathophysiologic mechanisms. MATERIALS AND METHODS: We report a patient with retinitis pigmentosa (RP) with ICS due to a mutation in the male germ cell-associated kinase (MAK) gene. RESULTS: A 41-year-old Ashkenazi Jewish male was referred for abnormal visual field revealed by regular optometric examination. His visual acuity was 20/20 in each eye. Dilated examination revealed typical finding of RP. Optical coherence tomography showed cystoid changes in each fovea. Photoreceptors were also degenerated. Intravenous fluorescein angiography showed no leakage. Genetic testing identified a homozygous mutation in the MAK gene: a 353-bp Alu insertion (K429insAlu). CONCLUSIONS: Mak regulates microtubule stability via phosphorylating RP1. Abnormal Mak may impact retinal photoreceptor ciliary length and subcompartmentalization. Mak is required for the survival of photoreceptors in mice. ICS has been reported in other ciliopathies. We report the first case of ICS due to mutation in MAK.

5-Fluorouracil-Induced Apoptosis Changes in Cultured Corneal Epithelial Cells.

PURPOSE: Repeated subconjunctival injections with 5-fluorouracil (5-FU) after trabeculectomy are used in glaucoma patients for the inhibition of overproliferation in wound site. Thus, a certain amount of the drug may penetrate into epithelial layer, where it causes toxicity to corneal epithelial cells. The aim of this study was to evaluate the toxic effects of 5-FU and mechanisms of drug-induced apoptosis in cultured corneal epithelial cells. METHODS: Cellular damage and the caspase pathway were estimated with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptotic characteristics were detected by flow cytometry, a TUNEL test, and western blotting in cultured corneal epithelial cells. RESULTS: The results indicated that 5-FU was toxic to corneal epithelial cells in a time- and dose-dependent manner. Pretreatment with a general caspase inhibitor (Z-VAD-FMK), a caspase-8 inhibitor (Z-IETD-FMK), and a caspase-9 inhibitor (Z-LEHD-FMK) reversed 5-FU-induced cellular damage. Following exposure to 5-FU, a flow cytometric assay with MitoLight dye demonstrated the significant loss of mitochondrial membrane potential. A positive TUNEL test revealed that cellular DNA apoptosis occurred following exposure to 0.5, 1, and 5 mg/mL 5-FU for 15 h. Positive annexin V-FITC and negative propidium iodide (PI) staining indicated that the cell membrane exhibited apoptosis upon exposure to 1 and 5 mg/mL 5-FU for 15 h. The western blot assay demonstrated upregulation of the p21 protein but downregulation of the Bcl-2 proteins induced by 5-FU. CONCLUSION: These data reveal that 5-FU-induced cellular apoptosis in corneal epithelial cells may be mediated through caspase-8, caspase-9, and mitochondria-regulated pathways, as well as by upregulation of p21 and downregulation of Bcl-2-dependent signal transduction pathways.

The oculocardiac reflex during strabismus surgery: its relationship to preoperative clinical eye findings and subsequent postoperative emesis.

PURPOSE: To compare the occurrence of significant bradycardia due to the oculocardiac reflex (OCR) during strabismus surgery and its relationship to preoperative clinical eye findings and subsequent development of postoperative emesis. METHODS: The medical records of consecutive patients who underwent strabismus surgery August 2006 to June 2009 were retrospectively reviewed. OCR was defined as presence of dysrhythmia or a sudden heart rate decrease ≥ 20% after traction on the extraocular muscle. OCR incidence was compared between the first, second, and third (if any) extraocular muscles in patients who had multiple-muscle strabismus surgery and also between specific muscles (eg, medial rectus vs lateral rectus muscle). Associations with OCR were compared for different strabismus types. Vomiting was considered postoperative if it occurred before discharge of the patient at noon on the day following surgery. Risk factors for OCR and postoperative vomiting were evaluated by logistic regression analysis. RESULTS: A total of 111 records were reviewed; 41 patients (37%) experienced OCR. Incidence of OCR and absence of OCR during traction of the first muscle were significantly associated with events during traction of the second (χ(2) = 36.681, P < 0.001) and third muscles (Fisher exact test, P = 0.030). The best predictors of OCR were the absence of fine stereopsis and a larger number of surgically treated muscles. Of the 111 patients, 30 (27%) who had postoperative vomiting, the best predictors were female sex and young age. CONCLUSIONS: In our cohort, patients experiencing intraoperative OCR when the first extraocular muscle was manipulated during multiple-muscle strabismus surgery were likely to experience it again during traction of additional muscles. More severe postoperative vomiting was common in these patients. OCR was associated with the preoperative absence of fine stereopsis.

Novel usage of intraocular pressure-lowering drugs as wound-healing inhibitors after trabeculectomy with cell culture and animal models.

Inhibiting the healing of wounds to ensure that the aqueous humor can drain into the scleral space unimpeded and form a filtering bleb plays a crucial role in determining the success rate of glaucoma surgery. The aim of this study was to investigate the novel use, with cell culture and animal models, of some commercial intraocular pressure (IOP)-lowering drugs in inhibiting the healing of fibroblast wounds. The Tenon's fibroblasts of rabbits were cultured to evaluate 13 IOP-lowering drugs for cellular proliferation, collagen formation, and migration. These were measured using [(3)H]thymidine and [(3)H]proline uptake, and Transwell chambers. A preservative of benzalkonium chloride (BAK) was initially used, with 0.02% as a maximal original concentration. All of the drugs and the BAK were diluted from original commercial concentrations to 1/10, 1/100, and 1/1000. The more inhibitive drugs screened from the cell cultures were then selected for further short-term application during and after trabeculectomy surgeries had been performed on the rabbits. Expression of the proliferative cell nuclear antigen was immunohistochemically examined 3 and 7 days after surgery. The results revealed that the inhibitive effects of BAK in cellular [(3)H]thymidine and [(3)H]proline uptake, and cellular migration were only evident at 0.002% concentrations. Based on the results of the cell cultures, timolol, latanoprost, and unoprostone exhibited a greater inhibitory effect than the other drugs. Moreover, the animal studies showed that latanoprost and unoprostone significantly suppressed the positive expression of proliferative cell nuclear antigen around the operative excision area 7 days after the trabeculectomy surgeries. The results indicate that short-term use of some IOP-lowering drugs, such as latanoprost and unoprostone, may inhibit postoperative wound healing after glaucoma surgery.

Effects of patient- and operation-related factors on postoperative pain after orthognathic surgery.

PURPOSE: This study aimed to assess the association between patient- and operation-related factors and postoperative pain in patients undergoing intraoral vertical ramus osteotomy (IVRO) or IVRO + genioplasty (GeP) for the treatment of mandibular prognathism. MATERIALS AND METHODS: A visual analog scale (VAS) was used to evaluate postoperative pain for 2 days in 63 patients who underwent orthognathic surgery (42 IVRO and 21 IVRO + GeP). Correlations between VAS and patient age, sex, blood loss, operation time, and intraoperative reduction in blood parameters were assessed and compared between IVRO and IVRO + GeP procedures. RESULTS: Mean operation time and blood loss were 252.02 minutes and 99.64 mL in the IVRO group and 317.62 minutes and 187.86 mL in the IVRO + GeP group, respectively. Operation time, blood loss, and postoperative reduction in blood parameters were significantly greater in the IVRO + GeP group than in the IVRO group. Mean VAS scores on the first and second postoperative days were 3.02 and 1.33 in the IVRO group and 2.95 and 1.14 in the IVRO + GeP group. However, postoperative pain did not differ significantly between the IVRO and IVRO + GeP groups on the first or second postoperative day. CONCLUSIONS: Postoperative pain associated with orthognathic surgery was acceptable, controllable, and not different between IVRO and IVRO + GeP procedures.

Exercise behaviors in breast cancer survivors in Taiwan.

BACKGROUND: Although exercise is a recommended rehabilitation intervention for many breast cancer survivors, exercise activity after cancer treatment is rarely reported in this patient group in Taiwan. OBJECTIVE: The objectives of this study were to analyze trends in exercise activity in breast cancer survivors in Taiwan. INTERVENTIONS/METHODS: This prospective, longitudinal study with repeated-measures design used standardized instruments to measure trends in exercise activity but performed no treatments or interventions. RESULTS: Of the 196 breast cancer survivors who participated in this study, 39% regularly engaged in light-to-moderate intensity exercise for approximately 15 minutes per day throughout the 6-month period of the study. Of these, 40% indicated that their exercise stage had increased, and only 13% indicated that their exercise stage had decreased. The most common exercise activities were walking, hiking, calisthenics, folk dancing, chi kung and tai chi. Although most women reported that exercise made them feel better both physically and emotionally, most said that they exercised mainly for health maintenance reasons. CONCLUSIONS: Frequency, duration, and intensity of exercise significantly increased during the 6-month study but did not reach the recommended levels. Most women believed that physical activity enhanced their recovery from cancer treatment. IMPLICATIONS FOR PRACTICE: When planning patient education interventions for breast cancer survivors, healthcare professionals should consider not only the role of exercise in breast cancer recovery, but also trends in exercise behavior among breast cancer survivors. The findings of this study contribute to the literature on exercise trends in breast cancer survivors.

Extraocular muscle insertion positions and outcomes of strabismus surgery: correlation analysis and anatomical comparison of Western and Chinese populations.

BACKGROUND/AIMS: To compare the insertion locations of extraocular muscles between Taiwanese (Han Chinese) and Western populations and to determine whether anatomical differences warrant different surgical guidelines. METHODS: Insertion locations were compared between a Taiwanese population of subjects who had received surgical treatment for strabismus and a control group who had not. Insertion locations and surgical outcomes in the strabismus group were also compared with those reported in other countries. RESULTS: In Taiwanese subjects, extraocular muscle insertion locations were not significantly different between strabismus subjects and controls. However, the distances from the insertion location to the limbus of the inferior rectus, lateral rectus and superior rectus were significantly shorter in the Taiwanese subjects than in Western populations. CONCLUSION: Extraocular muscle insertion locations for the Taiwanese population in this study significantly differed from those reported in studies of Western populations. Therefore, surgical guidelines for performing lateral rectus recession to treat exotropia in Western populations may be inappropriate for Taiwanese and other Asian populations.

Baby oil therapy for uremic pruritus in haemodialysis patients.

AIMS: The purpose of this study was to investigate the effectiveness of chilled/un-chilled baby oil therapy for treating uremic pruritus in haemodialysis patients. BACKGROUND: Uremic pruritus affects 50-90% of haemodialysis patients, which makes it one of the most common medical problems in this population. Pruritus can cause skin infection, desquamation, pathological skin change, sleep disorder, anxiety, depression and social dysfunction. DESIGN: A prospective, pretest-post-test quasi-experimental design was used. METHODS: Haemodialysis patients with uremic pruritus were recruited and randomly assigned to one of three groups: experimental group 1 (chilled baby oil treatment; n = 30), experimental group 2 (un-chilled baby oil treatment; n = 31) and a control group (routine care only; n = 32). Participants in experimental group 1 and experimental group 2 were treated with chilled and un-chilled baby oil, respectively, for 15 minutes at least once daily for three weeks. The control group received no intervention other than standard care. Data collection included demographic data and itch severity. Medical records were also reviewed. RESULTS: The baseline characteristics of subjects in this study were as follows: 59% were male, mean age was 61·88 (SD 12·7) years, mean duration of haemodialysis was 5·31 years, mean duration of uremic pruritus was 40·58 (SD 37·8) months and mean intensity of uremic pruritus was mild. The anti-pruritic effects were significantly larger in subjects treated with either chilled or un-chilled baby oil than in those who received routine care. Anti-pruritic effects did not significantly differ between experimental group 1 and experimental group 2. CONCLUSIONS: The study confirmed that, for relieving pruritus in haemodialysis patients, either chilled or un-chilled baby oil is as effective as moisturising lotions and cooling soothing agents. RELEVANCE TO CLINICAL PRACTICE: Applying baby oil is a simple, safe, inexpensive and easily administered treatment for itchy skin in haemodialysis patients. By preventing or reducing uremic pruritus, baby oil treatment may also improve quality of life in this patient group.

Pleiotropic role of atorvastatin in regulation of human retinal pigment epithelial cell behaviors in vitro.

Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, possess pleiotropic effects that have been extended to modulation of various cellular behaviors. This study aimed at examining whether atorvastatin (AVN) modulates cell growth, adhesion, migration, and contraction of cultured human retinal pigment epithelium (RPE) cells. The in vitro effects of AVN on human RPE cells was analyzed in terms of cell proliferation, cell cycle, cell adhesion, migration, and contraction assays. The modulatory effect of AVN on TGF-ß2-triggered signaling was determined by Western blotting detection. AVN at submicromolar dose exhibited no prominent morphological alteration and cytotoxicity, whereas it elicited cytostatic effect at concentrations higher than 1 µM. Cell cycle analysis showed that AVN induced growth arrest in both G1 and G2/M phases. AVN at 1 µM or higher concentrations significantly suppressed RPE cell adhesion. Cell migration and 3D collagen contraction assays showed that AVN significantly suppressed RPE cell migration and contractility, respectively. Mechanistically, AVN treatment transiently up-regulated phosphorylation of Akt, ERK1/2, and p38 MAPK, whereas down-regulated that of JNK1. Intriguingly, AVN pretreatment prominently attenuated the TGF-ß(2)-mediated non-Smad signaling, including Akt, ERK1/2, p38 MAPK, and JNK1 phosphorylation. Besides, it directly reduced constitutive level of myosin regulatory light chain peptide MYL9 and mitigated the TGF-ß(2)-induced phosphorylation of myosin phosphatase-targeting subunit 1, MYPT1. These in vitro findings strongly suggest that AVN possesses pleiotropic function on RPE cells, including anti-proliferation, anti-adhesion, anti-migration as well as anti-contraction. In conclusion, AVN treatment may be considered a useful therapy for proliferative vitreoretinal diseases.

Predictors of exercise frequency in breast cancer survivors in Taiwan.

AIM: To apply social cognitive theory to elucidate factors that motivate change in exercise frequency in breast cancer survivors during the six months after completing cancer treatment. BACKGROUND: Exercise is now a well-recognised quality-of-life intervention in breast cancer survivors. However, only regular exercise yields long-term benefits. Motivations for exercise have not been analysed in Taiwan patients with cancer. DESIGN: A prospective, longitudinal and repeated measures design was used. METHODS: A convenience sample of 196 breast cancer survivors was recruited from hospitals in metropolitan areas of north and south Taiwan. Study participants were allowed to select their preferred exercised activities. Exercise behaviour and other factors were then recorded using various standardised instruments. Medical charts were also reviewed. Data were analysed by a linear mixed model and by hierarchical multiple regression equations. RESULTS: Exercise frequency significantly changed over time. Explained variance in exercise frequency change was modest. Baseline exercise frequency was the best significant predictor of exercise frequency during the six-month study. The study also identified possible age-related differences in the effect of social support on exercise. The effect of social support for exercise on exercise frequency was apparently larger in older subjects, especially those over 40 years old, than in younger subjects. Mental health, exercise barriers and exercise outcome expectancy significantly contributed to change in exercise frequency during the six-month study. CONCLUSIONS: The analytical results revealed several ways to increase exercise frequency in breast cancer survivors: (1) encourage exercise as early as possible; (2) improve health status and provide social support for exercise, especially in women aged 40 years or older; (3) reduce exercise barriers and promote mental health; (4) reinforce self-efficacy and positive expectations of exercise outcomes and (5) provide strategies for minimising fatigue in early stages of rehabilitation. Relevance to clinical practice. Social cognitive theory provides a useful framework for understanding the motivation to exercise in breast cancer survivors.

Geldanamycin and its analog induce cytotoxicity in cultured human retinal pigment epithelial cells.

Geldanamycin (GA), a benzoquinone ansamycin, was originally isolated as a natural product with anti-fungal activity. GA and its analogs, including 17-allylamino-demethoxy geldanamycin (17-AAG), are also known to block the function of a molecular chaperone, heat shock protein 90 (Hsp90). In light of their anti-tumor properties through direct cytotoxicity and anti-angiogenicity, GA has been previously demonstrated to suppress hypoxia-induced VEGF production in retinal pigment epithelium (RPE) cells, implicating its applicability in treating intraocular neovascularization. This study aimed at investigating the effectiveness of Hsp90 inhibitor treatment in suppressing proliferation of cultured human RPE cells and elucidating its underlying mechanism. Cultured RPE cells were treated with GA or 17-AAG and subjected for cell proliferation assay and cell cycle analysis. Expression of apoptotic regulators and survival signaling activity were monitored by Western blotting. The results showed that both GA and 17-AAG significantly inhibited RPE cell proliferation at micromolar levels. Treatment with GA and 17-AAG led to growth arrests in G1 and S phases, increased sub-G1 hypodipoid cell population, induced apoptotic cell death, and upregulated P53 and P21 expression, although the drug-induced Bcl-2 upregulation cannot prevent cell death. Additionally, GA and 17-AAG significantly suppressed constitutive contents of phosphorylated ERK1/2 and total Akt proteins, and completely abrogated wortmannin-sensitized Akt phosphorylation. In conclusion, GA and 17-AAG inhibit RPE cell proliferation and induce cytotoxicity, possibly through downregulating Akt- and ERK1/2-mediated signaling activities. They might potentially constitute a therapeutic agent for ocular disorders with RPE over proliferation, such as proliferative vitreoretinopathy.