Association between handgrip strength and depressive symptoms in patients undergoing hemodialysis: a cross-sectional study from a single Chinese center.

BACKGROUND: The relationship between handgrip strength (HGS) and depression in patients undergoing hemodialysis (HD) was unknown. Therefore, we aimed to clarify this association in a cohort of patients. METHODS: HGS was used as a representative indicator of muscle strength and was measured with a handheld dynamometer. Depressive symptoms were assessed with the self-reported Patient Health Questionnaire-9. A multivariable logistic regression model and restricted cubic spline analysis were used to assess the relationship between HGS and depression. RESULTS: The prevalence of depression in our study was 34% in 568 Chinese patients undergoing HD. Compared with patients in the lowest tertiles of absolute and weighted HGS, patients in the highest tertiles of HGS had an approximately 59% lower [odds ratio (OR) = 0.41, 95% confidence interval (CI) = 0.24-0.68; OR = 0.41, 95%CI = (0.24-0.69)] prevalence of depressive symptoms after multivariate adjustments. Besides, the risk of depression in hemodialysis patients decreased by 33% (OR = 0.67, 95%CI = 0.53-0.85) and 32% (OR = 0.68, 95%CI = 0.54-0.85) for each standard deviation increase in absolute HGS and weighted HGS, respectively. The prevalence of depressive symptoms decreased with both increasing absolute HGS and weighted HGS after multivariate adjustments (p for trend < 0.05). Furthermore, a linear dose-response relationship was observed between absolute HGS and weighted HGS and the prevalence of depressive symptoms (pnonlinearity>0.05). CONCLUSIONS: This study suggests that lower handgrip strength, a simple and modifiable parameter, is associated with a higher prevalence of depression in Chinese patients undergoing HD. Considering that depression is often unrecognized or underdiagnosed in HD patients, lowered muscle strength should be an important indicator and incentive for medical staff to screen for depression.

Removal of sulfadiazine from aqueous solution by in-situ activated biochar derived from cotton shell.

Phosphoric acid is used to in-situ activate biochar pyrolyzed by cotton shells to enhance the adsorption ability of sulfadiazine (SDZ). To confirm the optimum condition, different impregnation ratios and impregnation times were investigated. It was found that the biochar (BC) pyrolyzed under the condition of an impregnation ratio of 2.5 and an impregnation time of 6 h showed the highest performance for the removal of SDZ. The maximum adsorption ability was 86.89 mg/g at a temperature of 298 K. The pseudo-second-order model was used to disclose the adsorption process of SDZ by BCs. The experimental data were described by the Langmuir and Temkin isotherms at different temperatures. It was found that the sorption of SDZ was an exothermic process according to the thermomechanical analysis. The activated BC could be recycled for at least five times with a high removal rate of SDZ. Thus, activated BCs are regarded as promising adsorbents for SDZ removal.

Injection of immunoglobulin in the treatment process of children with severe pneumonia.

OBJECTIVE: To observe the effect of intravenous infusion of immune globulin in the treatment of children with severe pneumonia. METHODS: Ninety-eight children with severe pneumonia who received treatment in our hospital between April 2015 and December 2016 were selected, and they were grouped into a control group and an treatment group, 49 each group. The control group received conventional treatment. The treatment group was additionally treated with immune globulin on the basis of conventional treatment. The humoral immune indicators were detected using immunoturbidimetric assay, and the inflammatory reaction indicators were detected using enzyme-linked immunoabsorbent kit. The overall efficacy, clinical symptoms, humoral immunity and inflammatory response were compared between the two groups. RESULTS: The total effective rate of the treatment group was significantly higher than that of the control group (P<0.05). The cough, rale and fever of the treatment group disappeared faster than those of the control group, the relief of cardiac failure was also faster in the treatment group (P<0.05). The immunoglobulin G (Ig G), Ig A and Ig M of patients in the two groups compared before treatment, and no significant difference was found (P>0.05). The Ig G level of the treatment group was higher than that of the control group after treatment (P<0.05). The comparison of Ig A and Ig M between the two groups indicated no significant difference (P>0.05). The two groups had no significant differences in the content of tumor necrosis factor (TNF)-α, C-reactive protein (CRP), soluble intercellular adhesion molecule (SICAM)-1 and interferon (IFN)-γ (P>0.05) before treatment, but the content of the treatment group was significantly higher than that of the control group (P<0.01). CONCLUSION: Immunoglobulin was significantly effective in the adjuvant treatment of children with severe pneumonia, and it can rapidly improve the improvement of symptoms, enhance immune function and inhibit inflammatory reaction; therefore it is worth promotion.

Pidotimod in the treatment of pediatric recurrent respiratory tract infection.

OBJECTIVE: To observe the clinical efficacy of pidotimod in the treatment of recurrent respiratory tract infection in children. METHODS: One hundred thirty-two patients with recurrent respiratory tract infection who received treatment in Tianan City Central Hospital were selected and divided into an observation group and a control group using random number table, 66 in each group. Patients in the control group were given conventional treatment, while patients in the observation group were given conventional treatment and pidotimod treatment; the clinical efficacy of the two therapies was compared. The levels of IgG and IgM were measured after treatment. RESULTS: The vital signs and the content of inflammatory mediator and Th1/Th2 in serum before and after treatment were compared, and the clinical efficacy of the two groups was evaluated. The fever, pulmonary rale, cough and antiadoncus of patients in the observation group disappeared earlier than those in the control group (P<0.05). The onset duration of respiratory tract infection and days of antibiotic application of the observation group were shorter than those of the control group after treatment (P<0.05). The times of infection of the observation group were less than that of the control group (P<0.05). Before treatment, the two groups had no significant difference in the content of inflammatory mediators and Th1/Th2 in the serum (P>0.05). The serum content of tumor necrosis factor (TNF)-α and interleukin (IL)-4 of the two groups one week after treatment was lower than that before treatment, and the content of interferon (IFN)-γ and IFN-γ/IL-4 were higher than that before treatment; moreover the observation group had lower serum content of TFN-α and IL-4 and lower content of IFN-γ and IFN-γ/IL-4 compared to the control group (P<0.05). The overall response rate of the observation group was 92.4%, much higher than 81.8% in the control group (P<0.05). CONCLUSION: Pidotimod has a remarkable efficacy in the treatment of pediatric recurrent respiratory tract infection because it can effectively inhibit the infection and optimize Th1/Th2 immune function.

Effectiveness and safety of recombinant human brain natriuretic peptide in the treatment of acute myocardial infarction in elderly in combination with cardiac failure.

OBJECTIVE: To investigate the effects and safety of recombinant human brain natriuretic peptide (rhBNP) in the treatment of elderly acute myocardial infarction induced cardiac failure. METHODS: One hundred and forty-six patients who were diagnosed as elderly acute myocardial infarction induced cardiac failure in the hospital from July 2014 to July 2015 were selected. They were divided into a test group and a control group, 73 each. Patients in both groups were given conventional treatment such as stabilization of atherosclerotic plaques, anti-platelet and remodeling and reversion of myocardium. The curative effects and the incidence of adverse reactions of the two groups were observed. RESULTS: The overall efficacy of the test group and the control group was 87.7% and 65.8% respectively, and the difference had statistical significance (P<0.05). The heart rate, urine volume, n-terminal pro-brain natriuretic peptide level and left ventricular ejection fraction (LVEF) of both groups significantly improved after treatment, and the improvement of the test group was superior to that of the control group (P<0.05). The serum creatinine of the test group remarkably reduced after treatment (P<0.05). The incidence of hypotension and arrhythmia of the test group was lower than that of the control group during hospitalization period (P<0.05). CONCLUSION: rhBNP can effectively relieve the clinical symptoms, cardiac function indexes and hemodynamic indexes of patients with elderly acute myocardial infarction induced cardiac failure, with a high safety. It can be extensively applied in the treatment of acute myocardial infarction in combination with cardiac failure.

[Construction and characterization of a gspL mutant of avian pathogenic Escherichia coli].

OBJECTIVE: To study the role of gspL gene in avian pathogenic Escherichia coli. METHODS: The gspL mutant of Avian pathogenic Escherichia coli (APEC) was constructed by homologous recombination assay. The growth characteristics, the ability of adhesion and invasion to DF1 cells, the virulence genes transcription level and median lethal dose (LD50) were analyzed between the gspL mutant strain and the wild strain. RESULTS: Compared with the wild strain, the mutant strain had no significant difference in the growth status. However, its ability of adhesion and invasion was significantly lower. The transcription of genes pfs, fyuA, iss and vat increased obviously, the tsh decreased and the transcription level of luxS, ibeA, stx2f and ompA had no significant change. LD50 showed that the gspL mutant strain had 12-fold increase in virulence. CONCLUSION: The deletion of gspL gene could abate the ability of adhesion and invasion, regulate and control some virulence gene transcription level, enhance the virulence of APEC. The results show that the gspL gene play roles in pathogenicity of APEC.

[Multiplex PCR assay for detection of virulence genes in avian pathogenic Escherichia coli].

OBJECTIVE: To efficiently study the virulence genes distribution of Avian pathogenic Escherichia coli (APEC), we developed four multiplex PCR to detect adhesin-associated genes, invasin and toxin-associated genes, serum resistance-associated genes and iron acquisition-associated genes. METHODS: According to gene sequences published in GenBank, we designed and synthesized 18 specific primer pairs, which were used in the four multiplex PCR. Then, we determined the sensitivity of multiplex PCR using diluted bacterial or DNA templates. To verify the feasibility of these multiplex PCR, we determined the distribution of virulence genes in 100 APEC isolates using these multiplex PCR. RESULTS: According to the results of PCR, we can conclude that each of the 18 genes was exactly and effectively amplified in the four multiplex PCR. The sensitivities of these four multiplex PCR were 10(3) Colony forming units (CFU), 10(3) CFU, 10(5) CFU, 10(5) CFU bacteria and 1ng, 1ng, 10ng and 10ng DNA, respectively. Furthermore, the results multiplex PCR for virulence genes distribution in 100 APEC were same as the single PCR. CONCLUSION: These results suggest that multiplex PCR developed in this study could efficiently detect the virulence genes of APEC, which was a useful and rapid technique for epidemiological investigation.

Characterization and functional analysis of AatB, a novel autotransporter adhesin and virulence factor of avian pathogenic Escherichia coli.

Autotransporter (AT) proteins constitute a large family of extracellular proteins that contribute to bacterial virulence. A novel AT adhesin gene, aatB, was identified in avian pathogenic Escherichia coli (APEC) DE205B via genomic analyses. The open reading frame of aatB was 1,017 bp, encoding a putative 36.3-kDa protein which contained structural motifs characteristic for AT proteins: a signal peptide, a passenger domain, and a translocator domain. The predicted three-dimensional structure of AatB consisted of two distinct domains, the C-terminal ß-barrel translocator domain and an N-terminal passenger domain. The prevalence analyses of aatB in APEC indicated that aatB was detected in 26.4% (72/273) of APEC strains and was strongly associated with phylogenetic groups D and B2. Quantitative real-time reverse transcription-PCR analyses revealed that AatB expression was increased during infection in vitro and in vivo. Moreover, AatB could elicit antibodies in infected ducks, suggesting that AatB is involved in APEC pathogenicity. Thus, APEC DE205B strains with a mutated aatB gene and mutated strains complemented with the aatB gene were constructed. Inactivation of aatB resulted in a reduced capacity to adhere to DF-1 cells, defective virulence capacity in vivo, and decreased colonization capacity in lung during systemic infection compared with the capacities of the wild-type strain. Furthermore, these capacities were restored in the complementation strains. These results indicated that AatB makes a significant contribution to APEC virulence through bacterial adherence to host tissues in vivo and in vitro. In addition, biofilm formation assays with strain AAEC189 expressing AatB indicated that AatB mediates biofilm formation.

[RmlA gene deletion affects biofilm formation by avian pathogenic Escherichia coli].

OBJECTIVE: To characterize rmlA gene inavian pathogenic Escherichia coli (APEC). METHODS: We constructed the rmlA mutant of APEC by the Red recombination system. Then we analyzed the differences of growth, movement and biofilm formation between mutant strain and wild strain. We compared the differences of virulence gene transcription between mutant strain and wild strain by real-time PCR. RESULTS: The rmlA mutant did not affect the growth and motility of APEC, but enhanced the biofilm formation significantly. In addition, the transcription level of some virulence genes in rmlA mutant showed that the luxS , irp2 were raised 2 and 1.6 times respectively, but decreased the iucD and fyuA by 25 times compared to the wild strain. CONCLUSION: These data indicate that the rmlA gene could strengthen the ability of APEC biofilm formation, and affect the transcription level of some virulence genes, but not the growth and motility.

[Spatial variations and the key driving factors of soil losses on dolomite slopes]. / ç™½äº‘å²©å¡åœ°åœŸå£¤æµå¤±ç©ºé—´åˆ†å¸ƒç‰¹å¾åŠå ³é”®å½±å“å› å­.

We selected a typical dolomite slope and set up three micro-plots (projection length was 2 m, width was 1.2 m) on the upper, middle, and lower slopes to analyze the variations of soil losses and the key influencing factors during two hydrological years (2020-2021). The results showed that soil losses at different slope positions on dolomite slopes followed an order of semi-alfisol in lower slopes (386 g·m-2·a-1) > inceptisol in middle slopes (77 g·m-2·a-1) > entisol in upper slopes (48 g·m-2·a-1). Downward along the slope, the positive correlation gradually increased between soil losses and surface soil water content, as well as rainfall, while it gradually decreased with the maximum 30 min rainfall intensity. The meteorological factors affecting soil erosion on the upper, middle and lower slopes were the maximum 30 min rainfall intensity, precipitation, average rainfall intensity and surface soil water content, respectively. Soil erosion processes on upper slopes were mainly driven by raindrop splash erosion and infiltration-excess runoff, while that on lower slopes were mainly driven by saturation-excess runoff. The volume ratio of fine soil in the soil profile was the key factor of soil losses on dolomite slopes, with an explanation rate of 93.7%. The lower slope was the key site of soil erosion in the dolomite slopes. Subsequent rock desertification management should be based on the erosion mechanism of different slope positions, while control measures should be arranged according to local conditions.

Biochar improves soil quality and wheat yield in saline-alkali soils beyond organic fertilizer in a 3-year field trial.

The objective of this study was to examine the effects of biochar compared to organic fertilizer on soil quality and wheat yield in the saline-alkaline lands. A 3-year field trial was conducted on moderately saline-alkaline land in the Yellow River Delta region (YRD) with six treatments: biochar (B1: 5 t, B2: 10 t, B3: 20 t ha-1 year-1) and organic fertilizer (OF1: 5 t, OF2: 7.5 t ha-1 year-1) as well as control (CK). The results showed that both biochar and organic fertilizer increased total organic carbon (TOC), total nitrogen (TN), NH4+-N, and NO3--N, and reduced pH, thereby increasing soil microbial biomass carbon (MBC) and nitrogen (MBN), MBC/TOC ratio, and MBN/TN ratio, but organic fertilizer increased soil nutrients and microbial biomass better than biochar. Correlation analysis revealed that soil water content (SWC), soil salt content (SSC), and Na+ were the most important factors influencing wheat yield. When compared to CK, the SSC and Na+ decreased by 5.55-7.52% and 3.86-9.39%, respectively, and SWC increased by 5.14-5.62% in the biochar treatment, while they increased by 1.07-10.19%, 1.08-7.58%, and 2.96-3.84% in the organic fertilizer treatment, respectively. Accordingly, wheat yield of biochar treatment was 0.90-14.71% higher than that of organic fertilizer treatment (4.49-4.80 t ha-1) and CK (4.47 t ha-1). Collectively, B2 had the lowest SSC and Na+ and the highest yield and was significantly better than the organic fertilizer treatment, as well as efficiently increasing soil nutrients and microbial biomass, suggesting that it may be a better agricultural practice for improving soil quality and increasing wheat yield in the YRD.

THE ROLE OF DNA DOUBLE-STRAND BREAK REPAIR THROUGH NON-HOMOLOGOUS END JOINING IN THE DOSE-RATE EFFECT IN TERMS OF CLONOGENIC ABILITY.

It is generally and widely accepted that the biological effects of a given dose of ionizing radiation, especially those of low linear energy transfer radiations like X-ray and gamma ray, become smaller as the dose rate becomes lower. This phenomenon, known as 'dose-rate effect (DRE),' is considered due to the repair of sublethal damage during irradiation but the precise mechanisms for DRE have remained to be clarified. We recently showed that DRE in terms of clonogenic cell survival is diminished or even inversed in rodent cells lacking Ku, which is one of the essential factors in the repair of DNA double-strand breaks (DSBs) through non-homologous end joining (NHEJ). Here we review and discuss the involvement of NHEJ in DRE, which has potential implications in radiological protection and cancer therapeutics.

Enhanced removal of hydrogen sulfide using novel nanofluid system composed of deep eutectic solvent and Cu nanoparticles.

The H2S removal performances of four deep eutectic solvent (DES) based nanofluid (NF) systems were measured using dynamic absorption experiment. The Cu containing NF system is found to be an excellent absorbent for H2S removal with a significantly enhanced desulfurization performance compared with DES original solution. Besides, the NF systems have relatively high regeneration performance. The NF systems and Cu nanoparticles before and after absorption as well as after regeneration were characterized by Fourier transform infrared (FT-IR) spectra, scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), transmission electron microscope (TEM) and energy dispersive spectrum (EDS). It is found that the ethanolamine, choline cation and sulfur were accumulated on the surface of Cu nanoparticles after absorption, and the bulk elements on the surface were identified as Cu and S after regeneration. The S-2 was existed in the form of Cu2S, and some sulfur was oxidized to zero-valent sulfur after regeneration.

Enhancement effect of nanofluids on the desulfurization and regeneration performance of ionic liquid-based system.

The desulfurization and regeneration performance of nanofluids composed of oxidizing ionic liquids and four inert nanoparticles are investigated. The addition of different nanoparticles has been proved to have enhancement effect on the H2S removal performance of oxidizing ionic liquids. The nanofluids with SiO2 nanoparticles showed the most significant strengthening desulfurization performance as well as regeneration performance. The optimal weight ratio of SiO2 nanoparticles in nanofluids was confirmed as 0.5%. The regeneration efficiency of the optimal nanofluid system can exceed 88%, which is far higher than that before the addition of SiO2 nanoparticles. The mass transfer coefficient increased significantly after the addition of nanoparticles. The nanoparticles and nanofluids before and after absorption were characterized by Fourier transform infrared spectra, nuclear magnetic resonance, scanning electron microscope, transmission electron microscope, energy dispersive spectrum and X-ray photoelectron spectroscopy. It was found that the structure and morphology of SiO2 nanoparticles remained basically unchanged in the absorption-regeneration process. The main final desulfurization product was identified as sulfate.

Possible relationship between mitochondrial changes and oxidative stress under low dose-rate irradiation.

Objectives: High dose-rate ionizing radiation (IR) causes severe DSB damage, as well as reactive oxygen species (ROS) accumulation and oxidative stress. However, it is unknown what biological processes are affected by low dose-rate IR; therefore, the molecular relationships between mitochondria changes and oxidative stress in human normal cells was investigated after low dose-rate IR.Methods: We compared several cellular response between high and low dose-rate irradiation using cell survival assay, ROS/RNS assay, immunofluorescence and western blot analysis.Results: Reduced DSB damage and increased levels of ROS, with subsequent oxidative stress responses, were observed in normal cells after low dose-rate IR. Low dose-rate IR caused several mitochondrial changes, including morphology mass, and mitochondrial membrane potential, suggesting that mitochondrial damage was caused. Although damaged mitochondria were removed by mitophagy to stop ROS leakage, the mitophagy-regulatory factor, PINK1, was reduced following low dose-rate IR. Although mitochondrial dynamics (fission/fusion events) are important for the proper mitophagy process, some mitochondrial fusion factors decreased following low dose-rate IR.Discussion: The dysfunction of mitophagy pathway under low dose-rate IR increased ROS and the subsequent activation of the oxidative stress response.

Diminished or inversed dose-rate effect on clonogenic ability in Ku-deficient rodent cells.

The biological effects of ionizing radiation, especially those of sparsely ionizing radiations like X-ray and γ-ray, are generally reduced as the dose rate is reduced. This phenomenon is known as 'the dose-rate effect'. The dose-rate effect is considered to be due to the repair of DNA damage during irradiation but the precise mechanisms for the dose-rate effect remain to be clarified. Ku70, Ku86 and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are thought to comprise the sensor for DNA double-strand break (DSB) repair through non-homologous end joining (NHEJ). In this study, we measured the clonogenic ability of Ku70-, Ku86- or DNA-PKcs-deficient rodent cells, in parallel with respective control cells, in response to high dose-rate (HDR) and low dose-rate (LDR) γ-ray radiation (~0.9 and ~1 mGy/min, respectively). Control cells and murine embryonic fibroblasts (MEF) from a severe combined immunodeficiency (scid) mouse, which is DNA-PKcs-deficient, showed higher cell survival after LDR irradiation than after HDR irradiation at the same dose. On the other hand, MEF from Ku70-/- mice exhibited lower clonogenic cell survival after LDR irradiation than after HDR irradiation. XR-V15B and xrs-5 cells, which are Ku86-deficient, exhibited mostly identical clonogenic cell survival after LDR and HDR irradiation. Thus, the dose-rate effect in terms of clonogenic cell survival is diminished or even inversed in Ku-deficient rodent cells. These observations indicate the involvement of Ku in the dose-rate effect.

Study on the desulfurization performance of iron/ethanolamine/deep eutectic solvent system.

Deep eutectic solvent (DES) was applied as the solvent of iron/alcohol amine system, and the prepared iron/ethanolamine/DES system was found to be a good desulfurizer for H2S removal. The absorbents were characterized by Fourier transform infrared spectroscopy. The iron/ethanolamine/DES system showed a significantly enhanced desulfurization performance compared with DES solution of iron or alcohol amine separately. Besides, the absorbents showed relatively stable desulfurization performance, which could keep a high H2S removal efficiency in a wide temperature range from 30-90°C. The iron/ethanolamine/DES system could be recycled for at least three times. The desulfurization product was analyzed by energy dispersive spectrum and X-ray diffraction, and the desulfurization product was identified as sulfur element.

Lack of sphingomyelin synthase 2 reduces cerebral ischemia/reperfusion injury by inhibiting microglial inflammation in mice.

Recanalization of blood flow after ischemia can lead to ischemia/reperfusion injury, and inflammation plays an important role in the mechanisms behind cerebral ischemia/reperfusion injury. Sphingomyelin synthase 2 (SMS2) deficiency reduces inflammation; however, the effect and mechanism of action of SMS2 on the inflammatory response after cerebral ischemia/reperfusion injury are still unclear. Wild-type (WT) and SMS2 knockout C57BL/6 mice were used to establish a model of cerebral ischemia/reperfusion. The neurological deficit score was evaluated with Longa's method, and infarct volume was evaluated by magnetic resonance imaging and 2,3,5-triphenyltetrazolium chloride staining. Neurological deficit and infarct volume were used to evaluate the degree of cerebral ischemia/reperfusion injury in mice. Western blotting, reverse transcription-quantitative PCR and immunofluorescence were used to detect the expression profiles. The neurological deficit score of SMS2-/- mice was significantly lower than that of WT mice at 72 h after cerebral ischemia/reperfusion injury (P=0.027), but not significantly different at 24 h (P=0.064). Compared with WT mice at 24 and 72 h after cerebral ischemia/reperfusion, the infarct volume of SMS2-/- mice was decreased, the expression of pro-inflammatory cytokines galectin 3 and interleukin-1ß were decreased, the activation of microglia was decreased, and the nuclear translocation of NF-κB p65 was decreased, but the expression of the anti-inflammatory factor arginase 1 was increased. Lack of SMS2 in mice can help to reduce the inflammatory reaction by inhibiting the activation of NF-κB signaling pathway, further attenuating cerebral ischemia/reperfusion injury in mice.

FXR1 is a novel MRE11-binding partner and participates in oxidative stress responses.

Ataxia-telangiectasia (AT) and MRE11-defective Ataxia-telangiectasia-like disorder (ATLD) patients show progressive cerebellar ataxia. ATM, mutated in AT, can be activated in response to oxidative stress as well as DNA damage, which could be linked to disease-related neurodegeneration. However, the role of MRE11 in oxidative stress responses has been elusive. Here, we showed that MRE11 could participate in ATM activation during oxidative stress in an NBS1/RAD50-independent manner. Importantly, MRE11 was indispensable for ATM activation. We identified FXR1 as a novel MRE11-binding partner by mass spectrometry. We confirmed that FXR1 could bind with MRE11 and showed that both localize to the cytoplasm. Notably, MRE11 and FXR1 partly localize to the mitochondria, which are the major source of cytoplasmic reactive oxygen species (ROS). The contribution of FXR1 to DNA double-strand break damage responses seemed minor and limited to HR repair, considering that depletion of FXR1 perturbed chromatin association of homologous recombination repair factors and sensitized cells to camptothecin. During oxidative stress, depletion of FXR1 by siRNA reduced oxidative stress responses and increased the sensitivity to pyocyanin, a mitochondrial ROS inducer. Collectively, our findings suggest that MRE11 and FXR1 might contribute to cellular defense against mitochondrial ROS as a cytoplasmic complex.

Protective effects of histone deacetylase inhibition by Scriptaid on brain injury in neonatal rat models of cerebral ischemia and hypoxia.

BACKGROUND: Neonatal hypoxia-ischemia brain damage (HBID) can cause a series of neurological sequelae, such as movement and cognitive impairment, and there is currently no clinically effective treatment. Changes in epigenetic processes had been shown to be involved in the development of a series of neurodegenerative diseases, and HDAC inhibition by Scriptaid had been shown to reduce severe traumatic brain injury by suppressing inflammatory responses. This study investigated the protective effect of HDAC inhibition by Scriptaid after HBID. METHODS: We established the neonatal rat HBID model, and used intraperitoneal injection of HDAC inhibitor scriptaid as a treatment. 7 days after HBID, nuclear magnetic resonance imaging (MRI) was used to detect infarct volume. The otarod test, wire hang test and Morris water maze were used to evaluate the HBID model of neurobehavioral dysfunction. Immunoblotting, immunofluorescence, and quantitative real-time PCR (RT-qPCR) were used to detect gene expression. RESULTS: HDAC inhibition by Scriptaid treatment could not only reduce the infarct volume and neuronal degeneration in HBID rats, but also helped to improve their neurobehavioral dysfunction. 7 days after HBID, the expression of HDAC-1, HDAC-2 and HDAC-3 in the infarct volume of HBID + Veh group rats were much more than that in sham group (P<0.05), but Scriptaid could significantly inhibit those expression (P<0.05), and significantly increased the acetylation of H3 and H4 in HBID rats. In vivo and vitro results demonstrated that Scriptaid had no significant effect on oligodendrocyte MBP protein expression after OGD, but Scriptaid -treated microglia cultures had protective effects on OGD-treated OLG, M1 microglia suppressed OLG activity after OGD, and M2 enhanced its activity. In vivo experiments at 7 days after HBIDI injury showed that Scriptaid could promote the polarization of microglia into M2 microglia, reduced the expression of pro-inflammatory factors, and enhance the expression of anti-inflammatory cytokines. CONCLUSION: After HBID, HDAC inhibitor Scriptaid inhibits inflammatory responses and protects the brain by promoting the polarization of microglia in brain tissue to M2 microglia.