Irreducible anteromedial radial head dislocation without fracture caused by transposed biceps tendon in an adult: A case report and literature review.

Irreducible anteromedial radial head dislocation (IARHD) caused by transposed biceps tendon is rare. Delayed diagnosis and surgical failure often occur. A 46-year-old fisherman presented with 10 days history of painful swelling and restricted movement of his right elbow due to strangulation injury by a fishing boat cable. On examination, the images of right elbow reveals in a "semi-extended and pronated" elastic fixation position. Radiography and three-dimensional reconstruction CT reveals an isolated anteromedial radial head dislocation with extreme protonation of the radius and the bicipital tuberosity towards the posterior aspect of the elbow joint, and MRI shows biceps tendon wrapping around the radial neck, similar to umbilical cord wrapping seen in newborns. The Henry approach was applied for the first time to reduce the biceps tendon. The patient achieved a good functional recovery at 26 months, which represents the first reported case of IARHD without fracture caused by biceps tendon in an adult. In treatment of IARHD, attention should be paid to the phenomenon of biceps tendon transposition. Careful clinical examination, comprehensive imaging modalities, and appropriate surgical approach are the keys to successful management.

Saponins from Panax japonicus improve neuronal mitochondrial injury of aging rats.

CONTEXT: Panax japonicus is the dried rhizome of Panax japonicus C.A. Mey. (Araliaceae). Saponins from Panax japonicus (SPJ) exhibit anti-oxidative and anti-aging effects. OBJECTIVE: We evaluated the neuroprotective effects of SPJ on aging rats. MATERIALS AND METHODS: Sprague-Dawley rats (18-months-old) were randomly divided into aging and SPJ groups (n = 8). Five-month-old rats were taken as the adult control (n = 8). The rats were fed a normal chow diet or the SPJ-containing diet (10 or 30 mg/kg) for 4 months. An in vitro model was established by d-galactose (d-Gal) in the SH-SY5Y cell line and pretreated with SPJ (25 and 50 µg/mL). The neuroprotection of SPJ was evaluated via Nissl staining, flow cytometry, transmission electron microscopy and Western blotting in vivo and in vitro. RESULTS: SPJ improved the neuronal degeneration and mitochondrial morphology that are associated with aging. Meanwhile, SPJ up-regulated the protein levels of mitofusin 2 (Mfn2) and optic atrophy 1 (Opa1) and down-regulated the protein level of dynamin-like protein 1 (Drp1) in the hippocampus of aging rats (p < 0.05 or p < 0.01 vs. 22 M). The in vitro studies also demonstrated that SPJ attenuated d-Gal-induced cell senescence concomitant with the improvement in mitochondrial function; SPJ, also up-regulated the Mfn2 and Opa1 protein levels, whereas the Drp1 protein level (p < 0.05 or p < 0.01 vs. d-Gal group) was down-regulated. DISCUSSION AND CONCLUSIONS: Further research on the elderly population will contribute to the development and utilization of SPJ for the treatment of neurodegenerative disorders.

Comprehensive analysis of pedicle screw implantation in the C7 vertebra using computed tomography-based three-dimensional models.

BACKGROUND: From a biomechanical point of view, pedicle screws (PS) are better than other kinds of screws for implantation in the seventh cervical vertebra (C7). However, the application of PS is limited because of the high risk of severe complications. It is essential to define the optimal entry point and trajectory. The aim of this study was to comprehensively analyze the starting point and trajectory for C7 PS insertion using three dimensional (3D) models. METHODS: Overall, 60 subjects aged 18 to 67 years old were included. All CT images were used to construct 3D computer models of the C7 vertebrae. A new coordinate system was established for the next evaluation. The pedicle axis was calculated with respect to the entire pedicle; then, the ideal entry point, screw diameter and length, sagittal angle and lateral angle were assessed. RESULTS: All the ideal entry points were located at the medial superior to lateral notch (LN), and the mean distance between the entry point and LN was 5.86 ± 1.67 mm in the horizontal direction and 3.47 ± 1.57 mm in the vertical direction. The mean distance between the entry point and the middle point of the inferior edge of the C6 articular process (MP) was 0.74 ± 1.83 mm in the horizontal direction. The mean sagittal angle of the pedicle axis was 90.42°, and the mean pedicle transverse angle was 30.70°. The average diameter and length of the PS were 6.51 ± 0.76 mm and 31.58 ± 4.40 mm, respectively. CONCLUSIONS: This study provided a novel method to calculate the ideal starting point and trajectory for C7 PS insertion. These measurements may be helpful for preoperative planning. It is recommended that 3D CT imaging is used preoperatively to carefully evaluate the anatomy of each individual.

A review on partial-wave dynamics with chiral effective field theory and dispersion relation.

The description of strong interaction physics of low-lying resonances is out of the valid range of perturbative QCD. Chiral effective field theories (EFTs) have been developed to tackle the issue. Partial wave dynamics is the systematic tool to decode the underlying physics and reveal the properties of those resonances. It is extremely powerful and helpful for our understanding of the non-perturbative regime, especially when dispersion techniques are utilized simultaneously. Recently, plenty of exotic/ordinary hadrons have been reported by experiment collaborations, e.g. LHCb, Belle, and BESIII, etc. In this review, we summarize the recent progress on the applications of partial wave dynamics combined with chiral EFTs and dispersion relations, on related topics, with emphasis onππ,πK,πNandK̄Nscatterings.

Saponins from Panax japonicus attenuate cognitive impairment in ageing rats through regulating microglial polarisation and autophagy.

CONTEXT: Panax japonicus is the dried rhizome of Panax japonicus C.A. Mey. (Araliaceae). Saponins from Panax japonicus (SPJ) exhibit anti-inflammatory and antioxidative effects. OBJECTIVE: To explore the neuroprotective effect of SPJ on natural ageing of rat. MATERIALS AND METHODS: Sprague-Dawley (SD) rats 18-month-old were divided into ageing control, ageing treated with SPJ 10 or 30 mg/kg (n = 8). Five-month-old rats were taken as the adult control (n = 8). Rats were fed regular feed or feed containing SPJ for 4 months. Cognitive level was evaluated by Morris water maze (MWM) test. The mechanisms of SPJ's neuroprotection were evaluated by transmission electron microscope, western blot analysis, and immunofluorescence in vivo and in vitro. RESULTS: SPJ attenuated ageing-induced cognitive impairment as indicated by elevated number of times crossing the target platform (from 1.63 to 3.5) and longer time spent in the target platform quadrant (from 1.33 to 1.98). Meanwhile, SPJ improved the morphology of microglia and synapse, and activated M2 microglia polarisation including increased hippocampus levels of CD206 (from 0.98 to 1.47) and YM-1 (from 0.67 to 1.1), and enhanced autophagy-related proteins LC3B (from 0.48 to 0.82), Beclin1 (from 0.32 to 0.51), Atg5 (from 0.22 to 0.89) whereas decreased p62 level (from 0.71 to 0.45) of ageing rats. In vitro study also showed that SPJ regulated the microglial polarisation and autophagy. DISCUSSION AND CONCLUSIONS: SPJ improved cognitive deficits of ageing rats through attenuating microglial inflammation and enhancing microglial autophagy, which could be used to treat neurodegenerative disorders.

[Chikusetsu saponin â £a ameliorates myocardial hypertrophy of rats through regulating expression of miR199a-5p/Atg5].

The present study investigated the effects of chikusetsu saponin Ⅳa(CHS Ⅳa) on isoproterenol(ISO)-induced myocardial hypertrophy in rats and explored the underlying molecular mechanism. ISO was applied to establish a rat model of myocardial hypertrophy, and CHS Ⅳa(5 and 15 mg·kg~(-1)·d~(-1)) was used for intervention. The tail artery blood pressure was measured. Cardiac ultrasound examination was performed. The ratio of heart weight to body weight(HW/BW) was calculated. Morphological changes in the myocardial tissue were observed by HE staining. Collagen deposition in the myocardial tissue was observed by Masson staining. The mRNA expression of myocardial hypertrophy indicators(ANP and BNP), autophagy-related genes(Atg5, P62 and beclin1), and miR199 a-5 p was detected by qRT-PCR. Atg5 protein expression was detected by Western blot. The results showed that the model group exhibited increased tail artery blood pressure and HW/BW ratio, thickened left ventricular myocardium, enlarged myocardial cells, disordered myocardial fibers with widened interstitium, and a large amount of collagen aggregating around the extracellular matrix and blood vessels. ANP and BNP were largely expressed. Moreover, P62 expression was up-regulated, while beclin1 expression was down-regulated. After intervention by CHS Ⅳa at different doses, myocardial hypertrophy was ameliorated and autophagy activity in the myocardial tissue was enhanced. Meanwhile, miR199 a-5 p expression declined and Atg5 expression increased. As predicted by bioinformatics, Atg5 was a target gene of miR199 a-5 p. CHS Ⅳa was capable of preventing myocardial hypertrophy by regulating autophagy of myocardial cells through the miR-199 a-5 p/Atg5 signaling pathway.

Spinal cord injury in an adult patient with thoracic butterfly vertebra: a case report and review of the literature.

BACKGROUND: Butterfly vertebrae are a rare congenital vertebral anomaly. An overlap of this spinal anomaly with other diseases has been reported. However, to the authors' knowledge, the coexistence of butterfly vertebrae and spinal cord injury has not been reported in the literature. CASE PRESENTATION: A 42-year-old male was admitted to our emergency department after a motor vehicle accident. His complaint was back pain, and he was unable to move both lower limbs. Upon physical examination, the patient was not ambulatory. Sensory examination revealed the absence of sensation below the T12 level. The strength of the bilateral lower limbs was grade 0. The patient received a radiographic evaluation. The initial diagnosis was T11 fracture with complete paraplegia of the lower limbs. Magnetic resonance imaging (MRI) was then performed. Sagittal MRI demonstrated an isointense lesion on T1-weighted imaging and a high-signal spindle-like lesion on T2-weighted imaging of the spinal cord adjacent to the T11 vertebra. The fat-suppressed sequence also revealed hyperintensities of the cord. There was no evidence of acute injury of the T11 vertebral body except for cuneiform anterior wedging. The patient was ultimately diagnosed with complete paraplegia with a T11 butterfly vertebra. He underwent urgent posterior decompressive and fixation surgery from T10 to T12. His postoperative recovery was uneventful. CONCLUSIONS: The coexistence of a butterfly vertebra with spinal cord injury was reported for the first time. Although butterfly vertebrae may be incidentally detected, it is important to be familiar with their radiographic features to distinguish them from fractures.

The CtBP1-p300-FOXO3a transcriptional complex represses the expression of the apoptotic regulators Bax and Bim in human osteosarcoma cells.

C-terminal binding protein 1 (CtBP1), a well-known transcriptional corepressor, functions as an oncogene in multiple cancer types, including osteosarcoma, by modulating the transcription of many tumor suppressors, such as cadherin 1 (CDH1), phosphatase and tensin homolog (PTEN), Bcl2-associated X (Bax), Bcl-2-interacting mediator (Bim), and cyclin-dependent kinase inhibitor 1A (CDKN1A). However, it is still unclear how CtBP1 regulates the expression of these downstream targets. Here, we identified that CtBP1 is overexpressed in osteosarcoma cells and found that CtBP1 directly interacts with the transcription factor forkhead box O3 (FOXO3a) and the histone acetyltransferase p300 in vivo and in vitro. Through microarray analysis, we found that CtBP1 negatively regulates FOXO3a levels. In contrast to the CtBP1 level, the FOXO3a expression level was found to be significantly reduced in osteosarcoma cells. Knockdown of CtBP1 or overexpression of FOXO3a in U2OS cells resulted in different gene expression patterns, and the former caused upregulation of CtBP1 downstream target genes such as CDH1, PTEN, Bax, Bim, and CDKN1A, whereas the latter caused upregulation of Bax and Bim, but not CDH1, PTEN, and CDKN1A. Further analysis indicated that the CtBP1-p300-FOXO3a transcriptional complex specifically binds to the promoters of Bax and Bim. Inhibition of CtBP1 by the constitutive expression of Pep1-E1AWT peptide in U2OS and OSA cells reversed oncogenic phenotypes, including colony formation, cellular proliferation, and migration, and limited tumor growth in vivo. Together our results demonstrated that the CtBP1-p300-FOXO3a transcriptional complex represses the expression of the apoptotic regulators Bax and Bim in human osteosarcoma cells and that targeting CtBP1-mediated transcriptional events might be a potential therapeutic strategy for the osteosarcoma treatment.

[Improved effects of saponins from Panax japonicus on decline of cognitive function in natural aging rats via NLRP3 inflammasome pathway].

The aim of this paper was to investigate the effect of total saponins from Panax japonicus( SPJ) on cognitive decline of natural aging rats and its mechanism. Thirty male SD rats of eighteen month old were randomly divided into three groups: aged group,10 mg·kg~(-1) SPJ-treated group and 30 mg·kg~(-1) SPJ-treated group. The SPJ-treated groups were given SPJ at the dosages of 10 mg·kg~(-1) and 30 mg·kg~(-1),respectively,from the age of 18 to 24 months. Aged group were lavaged the same amount of saline,10 six-month-old rats were used as control group,with 10 rats in each group. The open field test,novel object recognition and Morris water maze were performed to detect the changes of cognitive function in each group. The changes of synaptic transmission of long-term potentiation( LTP) in hippocampal CA1 region were detected by field potential recording. Western blot was used to detect the protein levels of NLRP3,ASC,caspase-1 and the changes of Glu A1,Glu A2,CAMKⅡ,CREB and phosphorylation of CAMKⅡ,CREB in each group.The results showed that SPJ could improve the decline of cognitive function in aging rats,reduce the damage of LTP in the hippocampal CA1 region of aged rats,and decrease the expression of NLRP3,ASC,caspase-1 in aging rats. At the same time,SPJ could enhance the membrane expression of AMPA receptor( Glu A1 and Glu A2),and increase the expression of p-CAMKⅡand p-CREB in aging rats.SPJ could improve cognitive decline of natural aging rats,and its mechanism may be related to regulating NLRP3 inflammasome,thus regulating the membrane expression of AMPA receptor,and enhancing the expression phosphorylation of CAMKⅡ and CREB.

[Effect of saponins extracted from Panax japonicas on inhibiting myocardial fibrosis by TGF-ß1/Smad3 signaling pathway in aging rats].

To investigate the amelioration effect of saponins extracted from Panax japonicas (SPJ) on myocardial fibrosis in natural aging rats and its mechanisms, male SD rats aged 18 months were randomly divided into 3 groups (aging model group, low-dose SPJ group and high-dose SPJ group), with 10 rats in each group. SPJ groups were given SPJ at different doses (10, 60 mg·kg⁻¹·d⁻¹) consecutively for 6 months, meanwhile, aging model group was treated with the equal volume of saline for 6 months until 24 months old. Another 10 rats aged 6 month were used as young control group. The changes of myocardial morphological were observed by haematoxylin-eosin (HE) staining. Masson staining was used to observe the changes of collagen deposition in rat hearts. RT-PCR was used to detect the mRNA expression levels of myofibroblast marker α-SMA, collagen-related protein COL1α2, COL3α1 and matrix metalloproteinase MMP2, MMP9. Western blot was used to test the changes of the protein expressions of TGF-ß1, p-Smad3, IL-1ß and TNF-α in heart tissues. SPJ can effectively improve the arrangement of myocardial fibers, decrease inflammatory infiltration and reduce collagen deposition in aging rats. SPJ can effectively down-regulate the mRNA expression levels of COL1α2, COL3α1, α-SMA, MMP9, MMP2 and inhibit the protein expressions of TGF-ß1, p-Smad3, TNF-α, IL-1ß in the natural aging heart tissues. SPJ can effectively alleviate myocardial fibrosis in natural aging rats, and its mechanisms was related to the inhibition of the protein expressions of TGF-ß1, p-Smad3 and the reduction of myocardial inflammation in rat hearts.

[Protective effect of total saponins of Panax notoginseng combined with total flavonoids of epimedium on D-galactose-incuced senescence of H9c2 cell].

To investigate the protective effect of Panax notoginseng saponins combined with total flavonoids of epimedium on D-gal-induced senescence of H9c2 cells and explore its underlying mechanisms. The 50 mol•L⁻¹ D-gal was used to induce H9c2 cells senescence. Different concentrations of TPNS, TFE, and TPNS combined with TFE were used for 4 hours for pre-treatment. D-gal was used to stimulate H9c2 cardiac muscle cells for 24 h. Then in order to determine the best combined scheme, MTT was used to detect cell viability. Cell senescence was identified by ß-galactosidase staining. Levels of reactive oxygen species(ROS) was observed by DCFH-DA detection. The changes of mitochondrial membrane potential were identified by JC-1 detection. Protein levels of silentmating type information regulation 2 Homolog-1(SIRT1), peroxisomal proliferator-activated receptor-coactivator 1α(PGC-1α) and silentmating type information regulation 2 Homolog-3(SIRT3) were detected by western blot analysis. The results showed that TPNS(5 mg•L⁻¹) combined with TFE(5 mg•L⁻¹) had significant synergistic effect on H9c2 myocardial cell proliferation(Q=1.154), so 5 mg•L-1TPNS combined with 5 mg•L⁻¹ TFE was determined as the best scheme. The quantity of ß-galactosidase staining and the fluorescence intensity of ROS were apparently decreased in 5 mg•L⁻¹ TPNS combined with 5 mg•L⁻¹ TFE scheme. Meanwhile, it markedly increased the florescence intensity of mitochondrial membrane potential and enhanced the protein expression of SIRT1, PGC-1α and SIRT3. TPNS combined with TFE could protect H9c2 cells from D-gal-induced senescence. The mechanism might be related to adjusting the signal pathways of SIRT1/PGC-1α, SIRT3, adjusting the structure and function of mitochondria and reducing oxidative stress injury.

[Effect of saponins extracted from Panax japonicus on inhibiting cardiomyocyte apoptosis by AMPK/Sirt1/NF-κB signaling pathway in aging rats].

To investigate the effects of saponins extracted from Panax japonicus(SPJ) on cardiomyocyte apoptosis in natural aging rats and explore its underlying mechanisms. SD male rats were randomly divided into four groups: young control group, natural aging group, SPJ low dose group and SPJ high dose group, with 10 rats in each group. The rats in natural aging group, SPJ low and high dose groups were respectively treated with normal saline, SPJ 10 and 60 mg•kg-1•d-1 from the beginning of 18 month-old, 6 days per week for 6 months till 24 month-old. Then the animals were sacrificed. Their myocardial morphology changes were observed by using haematoxylin-eoin(HE) staining; cardiomyocyte apoptosis was tested by using Tunel assays; and the protein expression levels of Bcl-2, Bax, IL-1ß, TNF-α, AMPK, p-AMPK, Sirt1, and Ac-NF-κB p65 in myocardial tissues of rats were detected by Western blot. The results showed that SPJ could effectively improve the arrangement disorder of myocardial fibers, reduce the infiltration of inflammatory cells and inhibit cardiomyocyte apoptosis in natural aging rats. At the same time, SPJ could significantly inhibit the protein expression of Bax, IL-1ß, TNF-α and Ac-NF-κB p65, and increase the expression of Bcl-2, Bcl-2/Bax, p-AMPK/AMPK and Sirt1 in the heart tissues of natural aging rats. SPJ can effectively inhibit cardiomyocyte apoptosis in natural aging rats, and its mechanisms may be related with the regulation of inflammatory reaction by AMPK/Sirt1/NF-κB signaling pathway.

Chikusetsusaponin V attenuates lipopolysaccharide-induced liver injury in mice.

Chikusetsusaponin V (CsV), a saponin from Panax japonicus, has been reported to inhibit inflammatory responses in lipopolysaccharide (LPS)-induced macrophage cells. However, whether CsV could alleviate LPS-induced liver injury in vivo and the potential mechanisms involved remain unclear. In the present study, we investigated the anti-inflammatory effects of CsV on LPS-induced acute liver injury in mice and further explored the potential mechanisms involved. Our results showed that CsV significantly attenuated elevation of alanine transaminase (ALT) and aspartate aminotransferase (AST) levels and improved liver histopathological changes in LPS-induced mice. In addition, CsV decreased serum tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels and inhibited mRNA expressions of inducible nitric oxide synthase (iNOS), TNF-α and IL-1ß in LPS challenged mice. Furthermore, CsV inhibited nuclear factor kappa B (NF-κB) activation by downregulating phosphorylated NF-κB, IκB-α, ERK, c-Jun N-terminal kinase (JNK) and p38 levels in the liver tissue, which ultimately decreased nucleus NF-κB protein level. In conclusion, our data suggested that CsV could be a promising drug for preventing LPS challenged liver injury since it attenuated LPS-induced inflammatory responses, partly via inhibiting NF-κB and MAPK signaling pathways.

Could the X(3915) and the X(3930) Be the Same Tensor State?

By using a combined amplitude analysis of the γγ→DD̅ and γγ→J/ψω data, we demonstrate that the X(3915), which is quoted as a J(PC)=0(++) state in the Particle Data Group table, is favored by the data to be a J(PC)=2(++) state appearing in both channels, which means that the X(3915) and the X(3930) can be regarded as the same J(PC)=2(++) state. Meanwhile, the data also prefer a large helicity-0 contribution of this tensor resonance to the amplitudes instead of the helicity-2 dominance assumed by BABAR, which may indicate a sizable portion of non-qq̅ components in this state. Identifying the X(3915) with the X(3930) and abandoning the helicity-2 dominance for this tensor state are helpful for the further understandings of the properties of this state and also of the mysterious "XYZ" charmoniumlike resonances.

Chikusetsu saponin V attenuates MPP+-induced neurotoxicity in SH-SY5Y cells via regulation of Sirt1/Mn-SOD and GRP78/caspase-12 pathways.

Studies have shown that saponins from Panax japonicus (SPJ) possess neuroprotective effects. However, whether Chikusetsu saponin V (CsV), the most abundant member of SPJ, can exert neuroprotective effects against 1-methyl-4-phenylpyridinium ion (MPP+)-induced cytotoxicity is not known. In this study, we aimed to investigate the neuroprotective effects of CsV on MPP+-induced cytotoxicity in human neuroblastoma SH-SY5Y cells and explore its possible mechanisms. Our results show that CsV attenuates MPP+-induced cytotoxicity, inhibits ROS accumulation, and increases mitochondrial membrane potential dose-dependently. We also found that levels of Sirt1 protein and Mn-SOD mRNA significantly decreased in MPP+-treated group but were restored with CsV treatment in a dose-dependent manner. Furthermore, GRP78 protein and Caspase-12 mRNA levels were elevated by MPP+ exposure but reversed by CsV treatment. CsV inhibited the MPP+-induced downregulation of Bcl-2 and up-regulation of Bax in a dose-dependent manner and, thus, increased the ratio of Bcl-2/Bax. Overall, these results suggest that Sirt1/Mn-SOD and GRP78/Caspase-12 pathways might be involved in the CsV-mediated neuroprotective effects.

In vitro inhibitory effects of scutellarin on six human/rat cytochrome P450 enzymes and P-glycoprotein.

Inhibition of cytochrome P450 (CYP) and P-glycoprotein (P-gp) are regarded as the most frequent and clinically important pharmacokinetic causes among the various possible factors for drug-drug interactions. Scutellarin is a flavonoid which is widely used for the treatment of cardiovascular diseases. In this study, the in vitro inhibitory effects of scutellarin on six major human CYPs (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and six rat CYPs (CYP1A2, CYP2C7, CYP2C11, CYP2C79, CYP2D4, and CYP3A2) activities were examined by using liquid chromatography-tandem mass spectrometry. Meanwhile, the inhibitory effects of scutellarin on P-gp activity were examined on a human metastatic malignant melanoma cell line WM-266-4 by calcein-AM fluorometry screening assay. Results demonstrated that scutellarin showed negligible inhibitory effects on the six major CYP isoenzymes in human/rat liver microsomes with almost all of the IC50 values exceeding 100 µM, whereas it showed values of 63.8 µM for CYP2C19 in human liver microsomes, and 63.1 and 85.6 µM for CYP2C7 and CYP2C79 in rat liver microsomes, respectively. Scutellarin also showed weak inhibitory effect on P-gp. In conclusion, this study demonstrates that scutellarin is unlikely to cause any clinically significant herb-drug interactions in humans when co-administered with substrates of the six CYPs (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and P-gp.

[Protective Effect of Total Flavonoids of Epimedium on D-galactose-induced Senescence in H9c2 Cells].

OBJECTIVE: To investigate the protective effect of Total Flavonids of Epimedium (TFE) on D-galactose-induced H9c2 cells senescence and to explore the underlying mechanisms. METHODS: D-galactosed (50 mmol/L) were used to induce the aging of H9c2 cells. Different concentrations of TFE (5,25 and 50 µg/mL) were added into the medium before the use of D-galactosed. Cells senescence was identified by ß-galactosidase and the changes in cell morphology were observed. The activity of superoxide dismutase(SOD) and the content of malondial dehyde (MDA) were measured. Reactive oxygen species( ROS) was observed by DCFH-DA detection and the apoptosis was tested by Hochest. RESULTS: In the D-gal group,the number of ß-galactosidase-positive cells, the content of MDA and the fluorescence intensity of ROS were markedly increased. In the meanwhile,the chromatin was condensated and the apoptotic bodies were seen by using Hochest. Compared with the D-gal group, TFE apparently decreased the quantity of ß-galactosidase-positive cells, the content of MDA, and the florescence intensity of ROS, increased the activity of SOD, and enhanced the condition of chromatin. CONCLUSION: TFE can confront D-galactose-induced senescence in H9c2 cells by increasing the ability of antioxidant and reducing the number of apoptosis.

Efficacy and safety of linezolid in treating gram-positive bacterial infection in the elderly: a retrospective study.

Linezolid is commonly used for the treatment of drug-resistant Gram-positive bacterial infection. This study aimed to evaluate the efficacy and safety of linezolid in treating Gram-positive bacterial infection in the elderly from January 2010 to December 2012. Total 40 elderly patients (>60 years old) with Gram-positive bacterial infection were treated with linezolid and their demographic and clinical data were collected and analyzed. Among the 40 patients, 31 patients (77.5 %) were cured. Linezolid caused little adverse effects on liver and renal function. The main adverse effect was thrombocytopenia and its incidence was significantly associated with baseline platelet count and the duration of treatment (P < 0.05). Logistic regression analysis showed that the baseline platelet count <200 × 10(6)/mL, but not the age, the sex, the length of hospital stay, baseline levels of hemoglobin, alanine aminotransferase, or creatinine clearance rate was significantly associated with linezolid-induced thrombocytopenia. In conclusion, linezolid is effective to cure Gram-positive bacterial infection in the elderly and causes little adverse effects on liver and renal function. Timely monitoring of baseline platelet count may be helpful to guide the use of linezolid to avoid the occurrence of thrombocytopenia.

Icariin Ameliorates D-galactose-induced Cell Injury in Neuron-like PC12 Cells by Inhibiting MPTP Opening.

OBJECTIVE: Icariin (ICA) has a good neuroprotective effect and can upregulate neuronal basal autophagy in naturally aging rats. Mitochondrial dysfunction is associated with brain aging-related neurodegenerative diseases. Abnormal opening of the mitochondrial permeability transition pore (mPTP) is a crucial factor in mitochondrial dysfunction and is associated with excessive autophagy. This study aimed to explore that ICA protects against neuronal injury by blocking the mPTP opening and down-regulating autophagy levels in a D-galactose (D-gal)-induced cell injury model. METHODS: A cell model of neuronal injury was established in rat pheochromocytoma cells (PC12 cells) treated with 200 mmol/L D-gal for 48 h. In this cell model, PC12 cells were pre-treated with different concentrations of ICA for 24 h. MTT was used to detect cell viability. Senescence associated ß-galactosidase (SA-ß-Gal) staining was used to observe cell senescence. Western blot analysis was performed to detect the expression levels of a senescence-related protein (p21), autophagy markers (LC3B, p62, Atg7, Atg5 and Beclin 1), mitochondrial fission and fusion-related proteins (Drp1, Mfn2 and Opa1), and mitophagy markers (Pink1 and Parkin). The changes of autophagic flow were detected by using mRFP-GFP-LC3 adenovirus. The intracellular ultrastructure was observed by transmission electron microscopy. Immunofluorescence was used to detect mPTP, mitochondrial membrane potential (MMP), mitochondrial reactive oxygen species (mtROS) and ROS levels. ROS and apoptosis levels were detected by flow cytometry. RESULTS: D-gal treatment significantly decreased the viability of PC12 cells, and markedly increased the SA-ß-Gal positive cells as compared to the control group. With the D-gal stimulation, the expression of p21 was significantly up-regulated. Furthermore, D-gal stimulation resulted in an elevated LC3B II/I ratio and decreased p62 expression. Meanwhile, autophagosomes and autolysosomes were significantly increased, indicating abnormal activation of autophagy levels. In addition, in this D-gal-induced model of cell injury, the mPTP was abnormally open, the ROS generation was continuously increased, the MMP was gradually decreased, and the apoptosis was increased. ICA effectively improved mitochondrial dysfunction to protect against D-gal-induced cell injury and apoptosis. It strongly inhibited excessive autophagy by blocking the opening of the mPTP. Cotreatment with ICA and an mPTP inhibitor (cyclosporin A) did not ameliorate mitochondrial dysfunction. However, the protective effects were attenuated by cotreatment with ICA and an mPTP activator (lonidamine). CONCLUSION: ICA inhibits the activation of excessive autophagy and thus improves mitochondrial dysfunction by blocking the mPTP opening.

Evaluation of the pharmacokinetics and cardiotoxicity of doxorubicin in rat receiving nilotinib.

Doxorubicin (DOX) is a potent chemotherapy drug with a narrow therapeutic window. Nilotinib, a small-molecule Bcr-Abl tyrosine kinase inhibitor, was reported to reverse multidrug resistance (MDR) mediated by P-glycoprotein (P-gp) transmembrane transporters. The present study aimed to investigate nilotinib's affection on the steady-state pharmacokinetics, disposition and cardiotoxicity of DOX. A total of 24 male Sprague-Dawley rats were randomized into four groups (6 in each) and received the following regimens: saline, intravenous DOX (5mg/kg) alone, and DOX co-administrated with either 20 or 40mg/kg nilotinib. Blood was withdrawn at 12 time points till 72h after DOX injection and the concentrations of DOX and its metabolite doxorubicinol (DOXol) in serum and cardiac tissue were assayed by LC-MS-MS method. To determine the cardiotoxicity, the following parameters were investigated: creatine kinase, lactate dehydrogenase, malondialdehyde, and superoxide dismutase. Histopathological examination of heart section was carried out to evaluate the extent of cardiotoxicity after treatments. The results showed that pretreatment of 40mg/kg nilotinib increased the AUC0-t and Cmax of DOX and DOXol. However, their accumulation in cardiac tissue was significantly decreased when compared with the group that received DOX alone. In addition, biochemical and histopathological results showed that 40mg/kg nilotinib reduced the cardiotoxicity induced by DOX administration. In conclusion, co-administration of nilotinib increased serum exposure, but significantly decreased the accumulation of DOX in cardiac tissue. Consistent with in vitro profile, oral dose of 40mg/kg nilotinib significantly decreased the cardiotoxicity of DOX in rat by enhancing P-gp activity in the heart.