Characteristic cytokine profile of the aqueous humor in eyes with congenital cataract and pre-existing posterior capsule dysfunction.

Objectives: To investigate the characteristic cytokine profile of the aqueous humor in eyes with congenital cataract and pre-existing posterior capsule dysfunction (PCD). Methods: In this cross-sectional study, the enrolled eyes with congenital cataract and PCD were included in the PCD group, while those with an intact posterior capsule were included in the control group. Demographic data and biometric parameters were recorded. The levels of 17 inflammatory factors in the aqueous humor collected from the enrolled eyes were detected using Luminex xMAP technology, and intergroup differences in the collected data were analyzed. Results: The PCD group comprised 41 eyes from 31 patients with congenital cataract and PCD, whereas the control group comprised 42 eyes from 27 patients with congenital cataract and an intact posterior capsule. Lens thickness was significantly thinner in the PCD group than in the control group. However, the levels of monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-ß2 (TGF-ß2), and vascular endothelial growth factor (VEGF) were significantly higher in the PCD group than in the control group. Multivariate logistic regression confirmed that lens thickness and TGF-ß2 level were independent risk factors for PCD. Conclusion: A thinner lens thickness in eyes with congenital cataract and PCD could serve as a biometric feature of these eyes. The higher levels of MCP-1, TGF-ß2, and VEGF in eyes with PCD indicated a change in their intraocular inflammatory microenvironment, which possibly led to cataract progression. Lens thickness and TGF-ß2 level are independent risk factors for PCD.

Microbiota from healthy mice alleviates cognitive decline via reshaping the gut-brain metabolic axis in diabetic mice.

Diabetic cognitive decline has been associated with the gut microbial disorders, but its potential gut-brain axis mechanisms remain unclear. Herein we transplanted the gut microbiota from healthy mice into type 1 diabetic (T1D) mice and then investigated the effect of fecal microbiota transplantation (FMT) on cognitive function and the gut-brain metabolic axis. The results demonstrate that FMT from healthy mice effectively improved the learning and memory abilities in T1D mice, and significantly reduced neuroinflammation and neuron injury in the cortex and hippocampus. Moreover, FMT partly reversed the gut microbiota and gut-brain metabolic disorders, particularly glutamate metabolism. In vitro study, we found that glutamate notably decreased microglia activation and the expression levels of proinflammatory factor. Hence, our study suggests that glutamate serves as a key signal metabolite connecting the gut to brain and affects cognitive functions.

Gastrointestinal microbiome of ARDS patients induces neuroinflammation and cognitive impairment in mice.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a respiratory failure syndrome that can cause many complications, impacting patients' quality of life. Behavioral and cognitive disorders have attracted increasing attention in patients with ARDS, but its potential mechanisms are still elusive. METHODS: Herein we transferred the faecal microbiota from patients with ARDS caused by community-acquired pneumonia (CAP) to antibiotics-treated recipient male mice to explore the microbiota-gut-brain mechanisms. Behavioral functions of mice were evaluated by the open field test, Morris water maze and Y-maze test. The structure and composition of the gut microbiota were analyzed by using 16S rRNA sequencing analysis. Microglia, astrocyte and neuron in the cortex and hippocampus were examined via immunofluorescent staining. RESULTS: We found that the major characteristic of the intestinal flora in ARDS/CAP patients was higher abundances of Gram-negative bacteria than normal controls. The gut microbiota derived from ARDS/CAP patients promoted neuroinflammation and behavioral dysfunctions in mice. Mice who underwent fecal transplant from ARDS/CAP patients had increased systemic lipopolysaccharide (LPS), systemic inflammation, and increased colonic barrier permeability. This may adversely impact blood barrier permeability and facilitate microglia activation, astrocyte proliferation, and loss of neurons. CONCLUSIONS: Our study proposes the role of the microbiota-gut-brain crosstalk on ARDS/CAP-associated behavioral impairments and suggests the gut microbiota as a potential target for the protection of brain health in ARDS patients in clinical practice.

Role and mechanism of leukemia inhibitory factor receptor in cervical cancer invasion and metastasis.

OBJECTIVE: To investigate the relationships of leukemia inhibitory factor receptor (LIFR) with cervical cancer invasion and metastasis. METHODS: From January 2021 to December 2022, 45 patients treated for cervical cancer and lung metastases were identified. Western blotting was used to determine the expression of Hippo-YAP signaling pathway-related proteins. Meanwhile, 40 healthy Sprague-Dawley nude mice were used and evenly randomized into two groups, which were injected with LIFR-overexpressing (study group) or normal cervical cancer cells (control group). The lung tissue of nude mice was removed for hematoxylin-eosin staining, and the number of lung cell metastases in nude mice was counted. RESULTS: The highest LIFR mRNA expression was found in paracancerous tissue, followed by cervix cancer tissue and metastatic lesions. The study group exhibited higher LIFR, P-YAP, and P-TAZ protein expression and lower YAP and TAZ protein expression than the control group. The study group had a lower number of lung metastases than the control group. CONCLUSION: Decreased expression of LIFR and decreased phosphorylation of Hippo-YAP signaling pathway-related proteins might be the underlying mechanisms that promote lung metastasis of cervical cancer.

Amelioration of Obesity-Related Disorders in High-Fat Diet-Fed Mice following Fecal Microbiota Transplantation from Inulin-Dosed Mice.

The role of inulin in alleviating obesity-related disorders has been documented; yet, its underlying mechanisms still need to be further investigated. This study attempted to elucidate the causative link between the gut microbiota and the beneficial effect of inulin on obesity-related disorders via transferring the fecal microbiota from inulin-dosed mice to high-fat diet (HFD)-induced obese recipient mice. The results show that inulin supplementation can decrease body weight, fat accumulation, and systemic inflammation and can also enhance glucose metabolism in HFD-induced obese mice. Treatment with inulin reshaped the structure and composition of the gut microbiota in HFD-induced obese mice, as characterized by increases in the relative abundances of Bifidobacterium and Muribaculum and decreases in unidentified_Lachnospiraceae and Lachnoclostridium. In addition, we found that these favorable effects of inulin could be partially transferable by fecal microbiota transplantation, and Bifidobacterium and Muribaculum might be the key bacterial genera. Therefore, our results suggest that inulin ameliorates obesity-related disorders by targeting the gut microbiota.

A novel polysaccharide from Rubus chingii Hu unripe fruits: Extraction optimization, structural characterization and amelioration of colonic inflammation and oxidative stress.

Raspberry is used as a medicine food homology species and its polysaccharides are worthy being investigated and developed. In the present study, a novel polysaccharide of unripe raspberry fruits (pRCP) was extracted and characterized. The results show that pRCP was an acidic heteropolysaccharide and its Mw value was 74.86 kDa with a high homogeneity. The main chain of pRCP consisted of â†’ 3,6)-ß-Galp(1 â†’ and â†’ 5)-α-Araf(1→, and its side chain was composed of α-Araf(1 â†’ linked to the C3 position of â†’ 3,6)-ß-Galp(1 â†’. In addition, pRCP supplementation increased the gut microbial diversity and reduced harmful bacteria including Erysipelatoclostridium and Negativibacillus in high-fat diet (HFD)-fed mice. Treatment with pRCP also alleviated HFD-induced colonic inflammation and oxidative stress in mice. These beneficial effects can be transferred to recipient mice by faecal microbiota transplantation from pRCP-treated mice. Therefore, our study suggests that pRCP could be used as a potential prebiotics to improve intestinal health by modulating the gut microbiota.

Capsulotomy opening diameter outcomes in aphakic eyes after primary congenital cataract removal and its association.

Aim: To observe the change of capsulotomy opening diameter (COD) in aphakic eyes after primary congenital cataract removal and investigate its influencing factors. Methods: Ocular parameters, including corneal diameter (CD), axial length (AL), anterior and posterior COD (ACOD, PCOD), and age at surgery were recorded at primary congenital cataract removal and secondary intraocular lens implantation. The concentrations of 15 kinds of cytokines in aqueous humor samples collected at the primary surgery were detected. The change (Δ) of COD between two surgeries were described, and its association was analyzed. Results: Fifty eyes from 33 patients with congenital cataract who underwent primary and secondary surgery were enrolled. The changes in ACOD and PCOD were not statistically significant on the whole. ΔACOD was positively correlated with ΔCD and the concentrations of PDGF-AA, VEGF and TGF-ß1. The concentration of FGF-2 and the interval between two surgeries showed negative correlations with ΔACOD and ΔPCOD. Conclusion: COD in aphakic eyes kept changing after primary surgery. The positive correlation between ΔACOD and ΔCD manifested the enlargement of ACOD was influenced by lateral eye growth. Meanwhile, ΔACOD was also associated with cytokines, indicating postoperative inflammation promoted the ACOD constriction.

Potential Therapeutic Mechanism of Traditional Chinese Medicine on Diabetes in Rodents: A Review from an NMR-Based Metabolomics Perspective.

Traditional Chinese medicine (TCM) has been used to treat diabetes for a long time, but its application has not been widely accepted due to unstandardized product quality and complex pharmacological mechanisms. The modernization of TCM is crucial for its further development, and in recent years the metabolomics technique has largely driven its modernization. This review focuses on the application of NMR-based metabolomics in diabetic therapy using TCM. We identified a series of metabolic pathways that altered significantly after TCM treatment, providing a better understanding of the metabolic mechanisms of TCM for diabetes care.

Gender Specificity and Local Socioeconomic Influence on Association of GHR fl/d3 Polymorphism With Growth and Metabolism in Children and Adolescents.

Objective: Growth hormone receptor (GHR) mediates most GH biological actions. This study is aimed to evaluate whether GHR fl/d3 polymorphism contributes to the inter-individual variability of growth and metabolism in healthy children and adolescents. Methods: A total of 4,730 students aged 6-16 years from Yixing and Suqian City in China were included in this cross-sectional study. Height and body mass index (BMI) were transformed into the form of z-score corresponding to age and gender. Logistic regression was used to evaluate the associations of GHR fl/d3 polymorphism with height, BMI, metabolic traits, and hypertension by estimating the odds ratios (ORs) and 95% confidence intervals (CIs). Results: GHR d3 allele was inversely associated with overweight, total cholesterol (TC) and triglyceride (TG) levels (OR [95% CI] for overweight: 0.754 [0.593-0.959], P = 0.021; OR [95% CI] for TC: 0.744 [0.614-0.902], P = 0.003; OR [95% CI] for TG: 0.812 [0.654-0.998], P = 0.047). GHR d3 allele was associated with decreased odds of pre-hypertension in boys (OR [95% CI]: 0.791 [0.645-0.971], P = 0.025), but associated with increased odds of pre-hypertension and hypertension in girls (ORs [95% CIs]: 1.379 [1.106-1.719], P = 0.004; OR [95% CI]: 1.240 [1.013-1.519], P = 0.037). Interaction of GHR fl/d3 polymorphism with gender contributed to increased odds of pre-hypertension and hypertension (interactive ORs [95% CIs]: 1.735 [1.214-2.481], P = 0.003; OR [95% CI]: 1.509 [1.092-2.086], P = 0.013). Stratification analysis showed that the correlation tendencies of GHR fl/d3 polymorphism and BMI with age were different between two cities with discrepant economic development levels. Conclusion: GHR fl/d3 polymorphism is associated with growth, metabolism, and hypertension in children and adolescents with the gender specificity, and the genetic effect of GHR fl/d3 may be modified by the local socioeconomic levels.

Inclusive education of elementary students with autism spectrum disorders in Shanghai, China: From the teachers' perspective.

Given an increasing number of children with ASD, the need for inclusive education has rapidly increased in China. Since 2011, children with ASD have been eligible for inclusive education. However, little is known of the implementation process by key personnel. The purpose of the current study was to qualitatively explore elementary school teachers' experiences and perspectives on an inclusive education policy and practice for students with ASD. Participants were from 5 elementary schools in 2 districts in Shanghai. This study consisted of data collection in 2 phases. First, semi-structured, in-depth interviews were conducted with school psychologists and vice principals responsible for students' mental health for implementation of general inclusive education at each school. Second, focus groups of frontline teachers were assembled to hear their firsthand experiences. A thematic analysis was performed. Findings indicated that although all 5 schools had some ASD-related support, training and resources varied depending on whether learning in regular classrooms (LRC) was implemented. Frontline teachers in particular faced challenges implementing LRC, including the limited extent of LRC, tedious implementation procedures, and parents' misconceptions of LRC. Regardless of these challenges, frontline teachers tried to support students with ASD as much as they could. The current findings should help to advance the inclusive education policy in Shanghai, including increasing the availability of inclusive education resources and training for teachers, issuing specific LRC guidance, and reducing ASD-related stigma. This study is among the first to explore the implementation of inclusive education in urban China.

Preterm neonatal mortality in China during 2009-2018: A retrospective study.

In this retrospective analysis, we aimed to analyze the epidemic characteristics of neonatal mortality due to preterm birth at 28-36 weeks gestation in different regions from 2009 to 2018. Data were obtained from China's Under-5 Child Mortality Surveillance System (U5CMSS). The χ2 trend test, Poisson regression and the Cochran-Mantel-Haenszel method were used in this study. We found that 51.3%, 42.0% and 44.5% of neonate deaths were preterm infants, and immaturity was mainly attributed to 60.1%, 64.1% and 69.5% of these deaths, in the eastern, central and western regions, respectively. The preterm neonatal mortality rate due to immaturity dropped from 149.2, 216.5 and 339.5 in 2009 to 47.4, 83.8 and 170.1 per 100 000 live births in 2018, giving an average annual decline rate of 12.1%, 11.6% and 6.3% in the eastern, central and western regions, respectively, during the studying period. The relative risk of preterm neonatal mortality due to immaturity were 1.3 and 2.3 for the central regions and western regions in 2009-2010, ascending to 2.2 and 3.9 in 2017-2018. The proportion of preterm neonatal deaths with a gestational age <32 weeks was highest among the eastern region. There were significantly more preterm neonatal infants who were not delivered at medical institutions in the western region than in the eastern and central regions. The preterm infant, especially with gestational age <32 weeks, should receive the most attention through enhanced policies and programs to improve child survival. Priority interventions should be region-specific, depending on the availability of economic and healthcare resources.

Commentary review: challenges of intraocular lens implantation for congenital cataract infants.

As an indispensable part of congenital cataract surgery, intraocular lens (IOL) implantation in infantile patients has long-term positive impacts on visual rehabilitation, as well as postoperative complications inevitably. Timing of IOL implantation in infantile congenital cataract patients is not simply a point-in-time but a personalized decision that comprehensively takes age at surgery, risks of postoperative complications, and economic condition of family in consideration, and combines with choosing suitable IOL type and power. For infants with well-developed eyeballs and good systemic conditions, IOL implantation at six months of age or older is safe and effective. Otherwise, secondary IOL implantation may be a safer choice.

Effect of Curcumin Addition on the Properties of Biodegradable Pectin/Chitosan Films.

A pectin/chitosan matrix-loaded curcumin film (PCCF) with a deep eutectic solvent (DES) as the solvent and plasticizer was prepared in this study. Different quantities of curcumin (identified as PCCF-0, PCCF-1, PCCF-2. PCCF-3) were loaded on the pectin/chitosan film in order to evaluate their effects on the film properties. Results showed that curcumin could interact with the pectin/chitosan matrix and form a complex three-dimensional network structure. PCCF could promote the thickness, tensile strength, thermal properties, antioxidant and antiseptic capacities, but deteriorate the light transmission and elongation at the same time. The addition of curcumin would change the color of the film, without significantly affecting the moisture content. The tensile strength of PCCF-3 reached the maximum value of 3.75 MPa, while the elongation decreased to 10%. Meanwhile, the water-resistance properties of PCCF-3 were significantly promoted by 8.6% compared with that of PCCF-0. Furthermore, PCCF showed remarkable sustained antioxidant activities in a dose-dependent manner. PCCF-3 could inhibit DPPH and ABTS free radicals by 58.66% and 29.07%, respectively. It also showed antiseptic capacity on fresh pork during storage. Therefore, curcumin addition could improve the barrier, mechanical, antioxidant and antiseptic properties of the polysaccharide-based film and PCCF has the potential to be used as a new kind of food packaging material in the food industry.

Silencing MR-1 attenuates atherosclerosis in ApoE-/- mice induced by angiotensin II through FAK-Akt-mTOR-NF-kappaB signaling pathway.

Myofibrillogenesis regulator-1 (MR-1) is a novel protein involved in cellular proliferation, migration, inflammatory reaction and signal transduction. However, little information is available on the relationship between MR-1 expression and the progression of atherosclerosis. Here we report atheroprotective effects of silencing MR-1 in a model of Ang II-accelerated atherosclerosis, characterized by suppression focal adhesion kinase (FAK) and nuclear factor kappaB (NF-κB) signaling pathway, and atherosclerotic lesion macrophage content. In this model, administration of the siRNA-MR-1 substantially attenuated Ang II-accelerated atherosclerosis with stabilization of atherosclerotic plaques and inhibited FAK, Akt, mammalian target of rapamycin (mTOR) and NF-kB activation, which was associated with suppression of inflammatory factor and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in Ang II-treated vascular smooth muscle cells (VSMCs) and macrophages: siRNA-MR-1 inhibited the expression levels of proinflammatory factor. These studies uncover crucial proinflammatory mechanisms of Ang II and highlight actions of silencing MR-1 to inhibit Ang II signaling, which is atheroprotective.

[Modified osteotomy of olecranon for the management of inter-condylar fracture of the humerus].

OBJECTIVE: To explore the surgical method and clinical outcome of modified osteotomy of olecranon for the treatment of inter-condylar fracture of humerus. METHODS: From May 2007 to December 2012, 32 patients of intercondylar fracture of humerus were treated surgically through the approach of modified osteotomy of olecranon. The patients were 21 males and 11 females with a mean age of 46.3 years (ranged 18 to 65 years). Nineteen fractures occurred on the right extremity and 13 on the left extremity. According to the AO classification, type C1 fracture was found in 7, C2 in 11 and C3 in 14. Five patients suffered from open fracture (Gustilo type Iin 3, type II in 2). Other fractures occurred in 6 patients and the primary injury of nerve occurred 6. The healing of the osteotomy was evaluated with physical examination and plain X-ray film, and the function of elbow was assessed according to Cassebaum scale. RESULTS: All the patients were followed from 9 months to 5 years(average, 1.9 years). All the osteotomies healed at 7.4 weeks averagely after operation, and no nonunion, delayed union, fracture of ulna olecranon were found. Two cases had little pain on the elbow, heterotopic ossification occurred in 2 cases and cutting bone block loosed in 1 case. The function of the elbow showed excellent in 19 cases, good in 8, fair in 4 and poor in 1. CONCLUSIONS: The use of the approach of modified olecranon osteotomy for surgical management of intercondylar fracture of humerus has some advantages, it provides satisfactory stability with simple technical procedures avoiding inter-articular invasion, and it facilitates rehabilitation exercises and providing good results with low complication rates.

Simultaneous expression and transportation of insulin by supramolecular polysaccharide nanocluster.

Drug/gene transportation systems with stimuli-responsive release behaviors are becoming research hotspots in biochemical and biomedical fields. In this work, a glucose-responsive supramolecular nanocluster was successfully constructed by the intermolecular complexation of phenylboronic acid modified ß-cyclodextrin with adamantane modified polyethylenimine, which could be used as a biocompatible carrier for insulin and pCMV3-C-GFPSpark-Ins DNA which could express insulin co-delivery. Benefiting from the response capability of phenylboronic acid moiety toward glucose, the encapsulated insulin could be specifically released and the corresponding targeted DNA could efficiently express insulin in HepG2 cell, accompanied by the high-level insulin release in vitro. Our results demonstrate that the simultaneous insulin drug delivery and insulin gene transfection in a controlled mode may have great potential in the clinical diabetes treatments.

The Sirt1 activator SRT1720 attenuates angiotensin II-induced atherosclerosis in apoE⁻/⁻ mice through inhibiting vascular inflammatory response.

Activation of the silent mating type information regulation 2 homolog 1 (SIRT1) has been shown consistent antiinflammatory function. However, little information is available on the function of SIRT1 during Angiotensin II (AngII)-induced atherosclerosis. Here we report atheroprotective effects of sirt1 activation in a model of AngII-accelerated atherosclerosis, characterized by suppression pro-inflammatory transcription factors Nuclear transcription factor (NF)-κB and Signal Transducers and Activators of Transcription. (STAT) signaling pathway, and atherosclerotic lesion macrophage content. In this model, administration of the SIRT1 agonist SRT1720 substantially attenuated AngII-accelerated atherosclerosis with decreasing blood pressure and inhibited NF-κB and STAT3 activation, which was associated with suppression of inflammatory factor and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in AngII-treated VSMCs and macrophages: SIRT1 activation inhibited the expression levels of proinflammatory factor. These studies uncover crucial proinflammatory mechanisms of AngII and highlight actions of SIRT1 activation to inhibit AngII signaling, which is atheroprotective.

[Modified Stoppa approach in treatment of bilateral pubic branch fractures].

OBJECTIVE: To investigate the feasibility and effectiveness of modified Stoppa approach in treatment of bilateral pubic fractures of pelvic. METHODS: The therapeutic effects of 16 patients with bilateral pubic fractures treated through the modified Stoppa approach from January 2010 to January 2014 were summarized and analyzed, involved 11 males and 5 females with an average age of 40.5 years old ranging from 17 to 59 years. According to Tile classification, there were 8 patients with type A, 6 with type B and 2 with type C. For 16 pelvic fractures, the modified Stoppa approach was used exclusively 11 cases, in combination with the iliac fossa approach in 4 cases, and in combination with the posterior approach in 1 case. The operation incision length, operation time , intra-operative blood loss and postoperative complications were observed. The fracture reduction and post-operative function were assessed by Matta criteria and Majeed system respectively. RESULTS: The incision length of the modified Stoppa approach ranged from 8 to 10 cm (averaged in 9 cm). The operation time ranged from 75 to 135 minutes (averaged in 95 minutes). The intra-operative blood loss ranged from 400 to 900 ml (averaged in 600 ml). Sixteen patients were followed up from 7 to 18 months (averaged in 12.5 months). The fractures were all healed, the fracture healing time was 2.7 to 5 months (means 3.1 months). There were no infections, ectopic ossification, screw loosening, plate breakage and lateral ventral syndrome. According to Matta criteria for pubic fracture reduction, the result was excellent in 9 cases, good in 6, fair in 1. The Majeed function scores at 6 months after operation was 85.32±8.50; the result was excellent in 8 cases, good in 6 cases, fair in 2 cases. CONCLUSION: The modified Stoppa approach has characteristics of convenience and directness of incisions, clear operation field, easy reduction, few complications and fast recovery , it is an ideal choice in surgical treatment of bilateral pubic fractures.

α-Linolenic acid attenuates doxorubicin-induced cardiotoxicity in rats through suppression of oxidative stress and apoptosis.

Doxorubicin (DOX), a widely used anti-tumor drug, can give rise to severe cardiotoxicity by oxidative stress and cell apoptosis, which restricts its clinical application. α-Linolenic acid (ALA) has been shown to serve as a potent cardioprotective agent. The aim of this study was to explore the protective effects of ALA on DOX-induced cardiotoxicity and the underlying molecular mechanisms for this cardioprotection in rats. Rats were randomly divided into four groups and administrated with normal saline, ALA (500 µg/kg), DOX (2.5 mg/kg), or ALA (500 µg/kg) plus DOX (2.5 mg/kg) for 17 days. The results showed that DOX treatment significantly increased the heart weight/body weight, liver wet weight (WW)/dry weight (DW), lung WW/DW, serum levels of brain natriuretic peptide, creatine kinase-MB, lactate dehydrogenase, and cardiac troponin I, myocardial necrosis and myocardial malondialdehyde content, and induced the mRNA expression of Nrf2 in the nucleus, cleaved caspase-3, Bax, and superoxide dismutase (SOD). In addition, DOX led to a significant decrease in left ventricular end-diastolic volume, stroke volume, ejection fraction, SOD, glutathione-peroxidase, catalase, as well as the expression of Kelch-like ECH-associated protein 1 (Keap1) in the cytoplasm, phospho-AKT, phospho-ERK, and Bcl-2. Co-treatment with ALA significantly eliminated these changes induced by DOX except further reduction of Keap1 and elevation of Nrf2 and SOD mRNA. These results showed the cardioprotective effects of ALA on DOX-induced cardiotoxicity in rats. The mechanisms might be associated with the enhancement of antioxidant defense system through activating Keap1/Nrf2 pathway and anti-apoptosis through activating protein kinase B/extracellular signal regulated kinase pathway. Our results suggested a promising future of ALA-based preventions and therapies for myocardial damage after administration of DOX.

Autophagy induced by FTY720 promotes apoptosis in U266 cells.

Despite recent treatment advances, multiple myeloma (MM) remains incurable and patients develop a progressively relapsing disease with subsequent poor prognosis. Studies have shown FTY720 has activities against a number of hematological malignancies including MM, no reports about autophagy induced by FTY720 in MM. Therefore, we investigated the potential application of FTY720 on MM using U266 cell line. We observed that FTY720 could induce caspase-3 dependent apoptosis in a dose- and time-dependent manner in U266 cells. FTY720 caused apoptosis by down-regulating antiapoptotic proteins Mcl-1, bcl-2, survivin and cleavage of Bid. Interestingly, FTY720 induce autophagy which could promote the apoptosis in U266 cells. Furthermore, activation of reactive oxygen species (ROS) regulates FTY720 induced apoptosis and autophagy in U266 cells. The study implicated that FTY720 could be a good candidate for MM treatment.