Entrapment neuropathy of common peroneal nerve by fabella: A case report.

BACKGROUND: Neuropathy of the common peroneal nerve caused by compression by a fabella is an extremely rare form of compression neuropathy. Involving both the superficial and deep peroneal nerves, it usually manifests as either impaired sensation from the lower lateral leg to the top of the foot or drop foot, or as a combination of both. CASE SUMMARY: We report the case of a 58-year-old Asian female who presented with inversion of the right foot during the stance phase of gait without sensory complaints related to the lower leg. Electrodiagnostic testing revealed the neuropathy of the common peroneal nerve at the level of the knee, exclusively affecting the muscular branch of the superficial peroneal nerve. A neuromuscular ultrasound disclosed swelling of the right common peroneal nerve just before it crossed over a large fabella as well as atrophy and fatty infiltration of the right peroneus longus and peroneus brevis muscles. Surgical excision of the fabella and neurolysis were performed. Subsequently, the strength of the right foot evertors improved, but the unsteady gait with occasional falls persisted for nine months after the surgery. Therefore, another procedure was performed to transfer the split posterior tibialis tendon to the peroneus brevis in order to correct the gait. CONCLUSION: This is the first case of neuropathy of the common peroneal nerve caused by compression by a fabella affecting exclusively the muscular branch of the superficial peroneal nerve. Clinicians should be aware of this unusual peripheral neuropathy while evaluating and treating patients with gait disturbance.

A novel smart somatosensory wearable assistive device for older adults' home rehabilitation during the COVID-19 pandemic.

Background: Due to the Coronavirus disease 19 (COVID-19) related social distancing measures and health service suspension, physical activity has declined, leading to increased falling risk and disability, and consequently, compromising the older adult health. How to improve the quality of older adult life has become a crucial social issue. Objective: In traditional rehabilitation, manual and repetitive muscle training cannot identify the patient's rehabilitation effect, and increasing the willingness to use it is not easy. Therefore, based on the usability perspective, this study aims to develop a novel smart somatosensory wearable assistive device (called SSWAD) combined with wireless surface electromyography (sEMG) and exergame software and hardware technology. The older adult can do knee extension, ankle dorsiflexion, and ankle plantar flexion rehabilitation exercises at home. Meanwhile, sEMG values can be digitally recorded to assist physicians (or professionals) in judgment, treatment, or diagnosis. Methods: To explore whether the novel SSWAD could improve the older adult willingness to use and motivation for home rehabilitation, 25 frail older adult (12 males and 13 females with an average age of 69.3) perform the rehabilitation program with the SSWAD, followed by completing the system usability scale (SUS) questionnaire and the semi-structured interview for the quantitative and qualitative analyses. In addition, we further investigate whether the factor of gender or prior rehabilitation experience would affect the home rehabilitation willingness or not. Results: According to the overall SUS score, the novel SSWAD has good overall usability performance (77.70), meaning that the SSWAD makes older adult feel interested and improves their willingness for continuous rehabilitation at home. In addition, the individual item scores of SUS are shown that female older adult with prior rehabilitation experience perform better in "Learnability" (t = 2.35, p = 0.03) and "Confidence" (t = -3.24, p = 0.01). On the contrary, male older adult without rehabilitation experience are more willing to adopt new technologies (t = -2.73, p = 0.02), and perform better in "Learnability" (t = 2.18, p = 0.04) and "Confidence" (t = -3.75, p < 0.001) with the SSWAD. In addition, the result of the semi-structured interview shows that the operation of the SSWAD is highly flexible, thus reducing older adult burden during the rehabilitation exercise and using them long-term. Conclusion: This novel SSWAD receives consistently positive feedback regardless of the gender or prior rehabilitation experience of elders. The SSWAD could be used as a novel way of home rehabilitation for elders, especially during the COVID-19 pandemic. Older adult can do rehabilitation exercises at home, and physicians could make proper judgments or adjust suitable treatments online according to the sEMG data, which older adult can know their rehabilitation progress at the same time. Most importantly, older adult do not have to go to the hospital every time for rehabilitation, which significantly reduces time and the risk of infection.

Polo­like kinase 1 selective inhibitor BI2536 (dihydropteridinone) disrupts centrosome homeostasis via ATM­ERK cascade in adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare but malignant tumor. Surgical removal, radiotherapy and combined chemotherapy are commonly used to treat ACC. Despite efforts for several decades, the mortality rate of ACC remains high after treatments. Therefore, identifying a novel therapeutic molecule is important to increase the survival rate of patients with ACC. The centrosome is a microtubule organizing center, and it also functions as a signaling hub to coordinate cell cycle progression. Deficiencies in the regulation of centrosome copy numbers may cause cell cycle arrest or even apoptosis. BI2536 is a polo like kinase 1­selective inhibitor and has been tested for the treatment of several types of cancer, including lung, oral and gastric cancer. However, to the best of our knowledge, its effects on ACC have not yet been examined. The present study revealed that BI2536 inhibited Y1 ACC cell proliferation in a time­ and dose­dependent manner. BI2536 blocked cell cycle progression and also induced cell apoptosis as shown by flow cytometry. Furthermore, following BI2536 treatment, centrosome amplification was induced, which resulted in aberrant mitosis. In terms of the mechanism, BI2536 induced DNA damage as evidenced by γH2AX staining and comet assay, followed by activation of ATM serine/threonine kinase­ERK signaling to promote centrosome amplification. Therefore, the present study suggested that BI2536 could be used as an adjuvant therapy in the treatment of ACC, and also revealed the underlying molecular mechanism.

Convolutional Neural Networks to Classify Alzheimer's Disease Severity Based on SPECT Images: A Comparative Study.

Image recognition and neuroimaging are increasingly being used to understand the progression of Alzheimer's disease (AD). However, image data from single-photon emission computed tomography (SPECT) are limited. Medical image analysis requires large, labeled training datasets. Therefore, studies have focused on overcoming this problem. In this study, the detection performance of five convolutional neural network (CNN) models (MobileNet V2 and NASNetMobile (lightweight models); VGG16, Inception V3, and ResNet (heavier weight models)) on medical images was compared to establish a classification model for epidemiological research. Brain scan image data were collected from 99 subjects, and 4711 images were used. Demographic data were compared using the chi-squared test and one-way analysis of variance with Bonferroni's post hoc test. Accuracy and loss functions were used to evaluate the performance of CNN models. The cognitive abilities screening instrument and mini mental state exam scores of subjects with a clinical dementia rating (CDR) of 2 were considerably lower than those of subjects with a CDR of 1 or 0.5. This study analyzed the classification performance of various CNN models for medical images and proved the effectiveness of transfer learning in identifying the mild cognitive impairment, mild AD, and moderate AD scoring based on SPECT images.

Therapeutic potential of nanoceria pretreatment in preventing the development of urological chronic pelvic pain syndrome: Immunomodulation via reactive oxygen species scavenging and SerpinB2 downregulation.

Urological chronic pelvic pain syndrome (UCPPS) manifests as pelvic pain with frequent urination and has a 10% prevalence rate without effective therapy. Nanoceria (cerium oxide nanoparticles [CNPs]) were synthesized in this study to achieve potential long-term pain relief, using a commonly used UCPPS mouse model with cyclophosphamide-induced cystitis. Transcriptome sequencing analysis revealed that serpin family B member 2 (SerpinB2) was the most upregulated marker in mouse bladder, and SerpinB2 was downregulated with CNP pretreatment. The transcriptome sequencing analysis results agreed with quantitative polymerase chain reaction and western blot analysis results for the expression of related mRNAs and proteins. Analysis of Gene Expression Omnibus (GEO) datasets revealed that SerpinB2 was a differentially upregulated gene in human UCPPS. In vitro SerpinB2 knockdown downregulated proinflammatory chemokine expression (chemokine receptor CXCR3 and C-X-C motif chemokine ligand 10) upon treatment with 4-hydroperoxycyclophosphamide. In conclusion, CNP pretreatment may prevent the development of UCPPS, and reactive oxygen species (ROS) scavenging and SerpinB2 downregulation may modulate the immune response in UCPPS.

A multicenter study to compare the effectiveness of the inpatient post acute care program versus traditional rehabilitation for stroke survivors.

There is insufficient evidence to prove the effect of the Post-acute Care (PAC) program on post-stroke recovery. This study aimed to determine the effectiveness of the PAC versus traditional inpatient rehabilitation (non-PAC) for middle- and old-aged stroke survivors. This multicenter cohort study enrolled 334 stroke patients admitted for post-stroke rehabilitation. The outcome variables included the Barthel Index (BI), Functional Oral Intake Scale (FOIS), Mini Nutritional Assessment-Short Form (MNA-SF), EuroQoL-5D (EQ-5D), Lawton-Brody Instrumental Activities of Daily Living (ADL) Scale, and Mini-Mental State Examination (MMSE). The inverse-probability-of-treatment-weighting method was used to analyze the differences in outcomes between the PAC and non-PAC groups. The PAC group showed better improvements in BI, MNA-SF, EQ-5D, Instrumental ADL, and MMSE compared to the non-PAC group, with differences in effect sizes of 0.54 (95% confidence interval [CI] 0.38-0.71), 0.26 (95% CI 0.10-0.42), 0.50 (95% CI 0.33-0.66), 0.44 (95% CI 0.28-0.60) and 0.34 (95% CI 0.17-0.50), respectively. The PAC project showed more improvement in basic and instrumental ADL and status of swallowing, nutrition, and cognition than those of non-PAC, which had less length of stay restricted by the National Health Insurance. More studies are warranted to investigate the influence of hospital stay and duration from stroke onset on the PAC's effectiveness.

Intelligent Fall-Risk Assessment Based on Gait Stability and Symmetry Among Older Adults Using Tri-Axial Accelerometry.

This study aimed to use the k-nearest neighbor (kNN) algorithm, which combines gait stability and symmetry derived from a normalized cross-correlation (NCC) analysis of acceleration signals from the bilateral ankles of older adults, to assess fall risk. Fifteen non-fallers and 12 recurrent fallers without clinically significant musculoskeletal and neurological diseases participated in the study. Sex, body mass index, previous falls, and the results of the 10 m walking test (10 MWT) were recorded. The acceleration of the five gait cycles from the midsection of each 10 MWT was used to calculate the unilateral NCC coefficients for gait stability and bilateral NCC coefficients for gait symmetry, and then kNN was applied for classifying non-fallers and recurrent fallers. The duration of the 10 MWT was longer among recurrent fallers than it was among non-fallers (p < 0.05). Since the gait signals were acquired from tri-axial accelerometry, the kNN F1 scores with the x-axis components were 92% for non-fallers and 89% for recurrent fallers, and the root sum of squares (RSS) of the signals was 95% for non-fallers and 94% for recurrent fallers. The kNN classification on gait stability and symmetry revealed good accuracy in terms of distinguishing non-fallers and recurrent fallers. Specifically, it was concluded that the RSS-based NCC coefficients can serve as effective gait features to assess the risk of falls.

Molecular and morphological identification of a reptile-associated tick, Amblyomma geoemydae (Acari: Ixodidae), infesting wild yellow-margined box turtles (Cuora flavomarginata) in northern Taiwan.

The genetic identity and morphological features of a reptile-associated tick, Amblyomma geoemydae, were examined for the first time in Taiwan. The key morphological characters of male and female Am. geoemydae were photographed using a stereo microscope. The genetic identity was analyzed by comparing the 16S mitochondrial DNA gene sequences obtained from 11 Taiwan Am. geoemydae ticks with other Amblyomma species and three Ixodes species as outgroups. All the Taiwan specimens were genetically affiliated to a monophyletic group of Am. geoemydae and could be discriminated from other Amblyomma species. Our results provide the first distinguished colour figures and first genetic identification of adult Am. geoemydae ticks infesting turtles in Taiwan. The host range and vectorial capacity of Am. geoemydae for various tick-borne pathogens need to be further clarified in Taiwan.

Adipose-Derived Stem Cell-Incubated HA-Rich Sponge Matrix Implant Modulates Oxidative Stress to Enhance VEGF and TGF-ß Secretions for Extracellular Matrix Reconstruction In Vivo.

This study demonstrated both adipose-derived stem cells (ASCs) in vitro and in vivo combined with three-dimensional (3D) porous sponge matrices on implant wound healing. Sponge matrices were created from hyaluronic acid (HA), collagen (Col), and gelatin (Gel), constructing two types: HA-L (low content) and HA-H (high content), to be cross-linked with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). Fourier transform infrared spectroscopy method verified carboxyl groups of HA and amino groups of Col and Gel reacting between the raw materials and scaffolds to identify the successive cross-linking. The swelling ratios of two types of sponge matrices were analyzed by water absorption capabilities, and the results displayed both over 30-fold dry scaffold weight enhancements. In biodegradation tests, matrices were hydrolyzed over time by three cutaneous enzymes, hyaluronidase, lysozyme, and collagenase I. ASCs from rats were cultured within the HA-H scaffold, demonstrating higher antioxidative abilities and secretions on related genes and proteins compared to the other two groups. The ASC HA-H matrix promoted cell proliferation to stimulate capillary angiogenesis inducer secretions, including vascular endothelial growth factor (VEGF) and transforming growth factor-ß (TGF-ß). In vivo histological examinations showed ASCs from implanted HA-H implant transported into the subcutis, and rat skin cells also infiltrated into the original matrix zone to increase the extracellular matrix (ECM) reconstructions. Our experimental data revealed that the ASC HA-H sponge implant was effective in improving wound repair.

A Novel Biocompatible Herbal Extract-Loaded Hydrogel for Acne Treatment and Repair.

A novel herbal extract-loaded gel containing several biofunctional extracts, including green tea, Zingiber officinale Rosc, Phyllanthus emblica, and salicylic acid, was developed for acne vulgaris. These natural raw materials were blended with suitable dosages of gelatin and carboxymethyl cellulose (CMC) to produce a biocompatible herbal gel. The physical chemistry properties of the hydrogel were determined by Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), rheometry, and scanning electron microscopy (SEM), and the hydrogel showed good mechanical and morphological characteristics. The herbal extract-loaded hydrogel mimicked extracellular matrix properties and showed good antioxidant and anti-inflammatory properties and various advantages, serving as a potential wound dressing material because of its high moisture retention ability, wound exudate absorption behavior, and biocompatibility. It exhibited moderate-high antioxidative and anti-inflammatory qualities that were important for dermis wound closure. The clinical trial results showed that most patients experienced moderate to high healing rates, and four of twenty-four individuals (16.67%) had recovery area ratios greater than 80%. This herbal extract-loaded hydrogel has effective ingredients and excellent mechanical properties as a bioactive dressing agent for acne treatment.

Botulinum toxin injection for Cockayne syndrome with muscle spasticity over bilateral lower limbs: A case report.

BACKGROUND: Cockayne syndrome (CS) is a rare inherited disease characterized by progressive motor symptoms including muscle weakness, joint contracture, ataxia, and spasticity. Botulinum neurotoxin type A has been used for conditions such as dystonia and spasticity, but it has rarely been used in patients with CS. CASE SUMMARY: We report a 6-year-and-9-mo old girl diagnosed with CS who received an injection of botulinum neurotoxin type A to manage her difficulty with walking. A total dose of 210 units of botulinum neurotoxin type A was administered into the bilateral tibialis posterior and gastrocnemius muscles. To evaluate the treatment effects on spasticity, joint contracture, pain, and ataxia, measurement tools including the Modified Ashworth Scale, the passive range of motion, the Faces Pain Scale-Revised, and the Scale for the Assessment and Rating of Ataxia, were employed. The first week after the injection, the Modified Ashworth Scale score for the plantar flexors and foot invertors improved bilaterally, along with advancements in the passive range of motion of the bilateral ankles and a lower score for the Faces Pain Scale-Revised. These treatment effects persisted to the 8th week post-injection, but returned to baseline values at the 12th week post-injection, except for the pain scale. CONCLUSION: Botulinum toxin injection can thus be considered as a treatment option for lower extremity spasticity, joint contracture, and pain derived from CS.

Etoposide Triggers Cellular Senescence by Inducing Multiple Centrosomes and Primary Cilia in Adrenocortical Tumor Cells.

Etoposide (ETO) has been used in treating adrenocortical tumor (ACT) cells. Our previous study showed that ETO inhibits ACT cell growth. In the present study, we show that ETO treatment at IC50 (10 µM) inhibited ACT cell growth by inducing cellular senescence rather than apoptosis. Several markers of cellular senescence, including enlarged nuclei, activated senescence-associated ß-galactosidase activity, elevated levels of p53 and p21, and down-regulation of Lamin B1, were observed. We further found that ETO induced multiple centrosomes. The inhibition of multiple centrosomes accomplished by treating cells with either roscovitine or centrinone or through the overexpression of NR5A1/SF-1 alleviated ETO-induced senescence, suggesting that ETO triggered senescence via multiple centrosomes. Primary cilia also played a role in ETO-induced senescence. In the mechanism, DNA-PK-Chk2 signaling was activated by ETO treatment; inhibition of this signaling cascade alleviated multiple ETO-induced centrosomes and primary cilia followed by reducing cellular senescence. In addition to DNA damage signaling, autophagy was also triggered by ETO treatment for centrosomal events and senescence. Importantly, the inactivation of DNA-PK-Chk2 signaling reduced ETO-triggered autophagy; however, the inhibition of autophagy did not affect DNA-PK-Chk2 activation. Thus, ETO activated the DNA-PK-Chk2 cascade to facilitate autophagy. The activated autophagy further induced multiple centrosomes and primary cilia followed by triggering senescence.

The association between economic indicators and the incidence of tetraplegia from traumatic spinal cord injury in Taiwan.

BACKGROUND: Economic performance may affect public health parameters. This study aimed to determine the time trend of incidence of traumatic spinal cord injury (SCI) and its association with income, presented by GDP (gross domestic product) per capita. METHODS: This study was a retrospective observational study in Taiwan. Newly diagnosed SCI patients with moderate to severe disability from 2002 to 2015 were identified from the reimbursement database of the National Health Insurance (NHI) system (1998-2015). CIR16-99 (cumulative incidence rate, aged 16-99 years, per 103 person-years) and CIR16-59 (aged 16-59 years) of SCI from 2002 to 2015 were measured. RESULTS: There were 5048 newly diagnosed SCI patients during the study period. After controlling the factors of sex, urbanization level, literacy, income inequality, and global financial crisis (mixed effects models), the CIR16-99 of SCI, traumatic SCI, motor vehicle (MV)-related SCI, fall-related SCI, tetraplegia, traumatic tetraplegia, MV-related tetraplegia, and fall-related tetraplegia were inversely associated with GDP per capita; the ß coefficients ranged from - 4.85 (95% confidence interval - 7.09 to - 2.6) for total SCI to - 0.8 (- 1.3 to - 0.29) for fall-related tetraplegia. We restricted our comparison to Taipei City and the 4 lowest densely populated counties, which also corroborated with the above results. The income elasticity analysis revealed when GDP per capita increased by 1%, the total SCI decreased by 1.39‰; which was also associated with a decrease of 1.34‰, 1.55‰, 1.36‰, 1.46‰, 1.54‰, 1.54‰, and 1.62‰ for traumatic SCI, MV-related SCI, fall-related SCI, tetraplegia, traumatic tetraplegia, MV-related tetraplegia, and fall-related tetraplegia respectively. The ß coefficients show that the compared areas of urbanization level were also inversely correlated with CIR16-59 in the SCI population. CONCLUSIONS: We conclude that the incidence of tetraplegia of traumatic SCI in Taiwan decreases with good economic performance, which may be resulted from the provision of public goods and services, possibly through improvements in the infrastructure of transportation and construction.

Savings of loss-of-life expectancy and lifetime medical costs from prevention of spinal cord injuries: analysis of nationwide data followed for 17 years.

BACKGROUND: The objectives of this research were to determine the savings of loss-of-life expectancy (LE) and lifetime medical costs (LMC) from prevention of spinal cord injuries (SCI) in Taiwan. METHODS: From the claims database of Taiwan National Health Insurance, we identified 6164 adult patients with newly diagnosed SCI with permanent functional disability from 2000 to 2015 and followed them until the end of 2016. We estimated survival function through the Kaplan-Meier method and extrapolated it to lifetime. RESULTS: For the SCI cohort, the LE and loss-of-LE were 17.6 and 13.3 years, respectively, while those for SCI with coding of external causes (E-code) were 18.1 and 13.0 years, respectively. For the SCI cohort with E-code, the loss-of-LE of motor vehicle (MV)-related SCI was significantly higher than that of fall-related SCI. In young and middle-aged patients with SCI with E-code, the loss-of-LE of MV-related paraplegia was significantly higher than that of MV-related quadriplegia and fall-related SCI. With a 3% discount rate, the LMC for patients with SCI after diagnosis were US$82 772, while those for patients with SCI with E-code were US$81 473. The LMC and the cost per year for those living with quadriplegia were significantly higher than those for paraplegia in all age groups, possibly related to the higher frequencies of stroke, chronic lung disease and dementia. CONCLUSIONS: We conclude that quadriplegia has a higher impact on medical costs than paraplegia, and MV-related SCI has a higher impact on loss-of-LE than fall-related SCI. We recommend comprehensive SCI prevention be established, including infrastructures of construction and transportation.

Environmental Barriers and Functional Outcomes in Patients with Schizophrenia in Taiwan: The Capacity-Performance Discrepancy.

Environmental factors are crucial determinants of disability in schizophrenic patients. Using data from the 2014-2018 Certification of Disability and Care Needs dataset, we identified 3882 adult patients (46.78% females; age, 51.01 ± 13.9 years) with schizophrenia. We found that patients with severe schizophrenia had lower capacity and performance than those with moderate schizophrenia. The chances of having an access barrier to environmental chapter 1 (e1) products and technology in moderate schizophrenic patients and in severe schizophrenic patients were 29.5% and 37.8%, respectively. Logistic regression analyses demonstrated that the performance score was related to accessibility barriers in the categories described in e1, with adequate fitness of models in category e110 for personal consumption, e115 for personal usage in daily living activities, and e120 for personal outdoor and indoor mobility and transportation. Furthermore, the capacity-performance discrepancy was higher in moderate schizophrenic patients with accessibility barriers in the e110, e115, and e120 categories than that in moderate schizophrenic patients without accessibility barriers. However, severe schizophrenic patients with category e120 accessibility barriers were prone to a lower discrepancy, with institutional care a potentially decreasing factor. In conclusion, providing an e1 barrier-free environment is necessary for patients with schizophrenia to decrease their disability.

Chloroquine inhibits human retina pigmented epithelial cell growth and microtubule nucleation by downregulating p150glued.

Chloroquine (CQ) is an antimalaria drug that has been used in clinical practice for several decades. One serious complication of CQ treatment is the macular retinopathy caused by the disruption of the retinal pigmented epithelium, leading to vision loss. Little is known about how CQ affects retinal pigmented epithelium. In this study, we found that cell proliferation was reduced by CQ treatment in time and dose-dependent manners. No obvious cell death was detected; however, what was observed instead was G0/G1 arrest during which primary cilium started to grow in the presence of CQ. Pharmacological inhibition of primary cilium formation led to a reduction of cell viability suggesting that CQ-induced primary cilium protected cells from death. In addition to cell growth, with the CQ treatment the retina pigmented epithelium (RPE) cells less flattened with the spindle-like protrusion. When checking the microtubule networks, the microtubule nucleation activity was disrupted in the presence of CQ. The level of p150 glued , the largest subunit of dynactin, was reduced in CQ-treated RPE1 cells, and depletion of p150 glued resulted in a phenotype reminiscent of CQ-treated cells. Thus, CQ treatment reduced the expression of p150 glued , leading to reduced S phase entry and defective microtubule nucleation.

Study on Tripping Risks in Fast Walking through Cadence-Controlled Gait Analysis.

Fast walking is a common exercise for most people to promote health. However, a higher cadence due to fast walking on ordinary or uneven ground raises the risk of tripping. To investigate the tripping issue, research to observe the gait in fast walking is needed. To explore the relationship between fast gait and the risk of tripping, a gait recording system with a specific synchronization mechanism was developed in this work. The system can acquire gait signals from wearable sensors and action cameras at different cadences. Meanwhile, algorithms for gait cycle segmentation and characteristic extraction were proposed for analyzing a fast gait. In the gait analysis, the correlations of low, moderate, and high cadence in cueing and no cueing gaits were computed, and two results were obtained. First, the higher the cadence is, the larger the motion strength in the terminal foot swing will be and the smaller the motion strength at the starting foot swing. Second, the decreased distance of foot clearance becomes more conspicuous as the cadence increased, especially if one is walking more than 120 beats. The results indicate that fast walking with bigger strides and lower cadence is the best way to maintain safety in moving over ordinary ground.

7-hydroxy-staurosporine, UCN-01, induces DNA damage response, and autophagy in human osteosarcoma U2-OS cells.

Human osteosarcoma (bone cancer) is a highly malignant and the most prevalent bone tumor affecting children. Despite recent advances in the understanding of the molecular mechanism by which anticancer drugs kill osteosarcoma or block its growth, however, the mortality rate has declined only modestly. Thus, a new therapeutic approach is needed to be established. 7-hydroxystaurosporine, UCN-01, abrogates the G2 checkpoint thus enhancing the cytotoxicity of chemotherapeutic agents. In addition, it has been evaluated in clinical trials as a single antineoplastic agent in treating several cancers. However, the effects of UCN-01 on treating bone cancer has never been tested. In this study, we found that UCN-01 induced cell cycle arrest and apoptosis in the human osteosarcoma, U2-OS cells. In addition, the migration ability was also reduced, suggesting UCN-01 inhibited cell growth and migration. When U2-OS cells were treated with UCN-01, DNA damage response was triggered. The ataxia telangiectasia mutated (ATM) and the non-canonical downstream effector, ERK, was activated by UCN-01. In addition, depletion of ATM or inhibition of ERK deteriorated the cell viability in UCN-01-treated U2-OS cells. Furthermore, UCN-01 induced autophagy activation for protecting cells from apoptosis. Thus, UCN-01 might function as a single antineoplastic agent in treating human osteosarcoma.