Evaluation of adverse reactions induced by anti-tuberculosis drugs among hospitalized patients in Wuhan, China: A retrospective study.

The study aims to estimate the incidence and risk factors of adverse drug reactions (ADRs) induced by anti-tuberculosis (TB) drugs. A single center retrospective analysis of patients taking anti-TB therapy from January 2016 to December 2018 in the hospital was conducted. Univariate and multivariate logistic regression analysis were used to identify these risk factors of ADRs induced by anti-TB drugs. Among 1430 patients receiving anti-TB therapy, 440 (30.77%) patients showed at least 1 ADR induced by anti-TB drugs. Hyperuricemia was the most common ADR, followed by hepatic function test abnormality, liver damage and gastrointestinal reactions. Significant differences (P < .05) were also seen in diabetes, age, treatment duration, type of TB (extrapulmonary) and some therapeutic regimens between ADR group and non-ADR group, respectively. Multivariate logistic regression analysis showed that treatment duration (OR = 1.029, 95%CI[1.018-1.040], P = .000), type of TB (extrapulmonary, OR = 1.487, 95%CI[1.134-1.952], P = .004) and some therapeutic regimens (HREZ, OR = 1.425, 95%CI[0.922-2.903], P = .001; HRZS, OR = 2.063, 95% CI[1.234-3.449], P = .006; HRZ, OR = 3.623, 95%CI[2.289-5.736], P = .000) were risk factors for ADRs induced by anti-TB drugs. Anti-TB drugs usually induced the occurrence of severe and frequent adverse effects, such as hyperuricemia. Treatment duration, HREZ, HRZS and HRZ regimens, and type of TB (extrapulmonary) should be considered as high-risk factors. Thus, it should be recommended to consider optimum management during anti-TB therapy, particularly hyperuricemia monitoring and hepatic function test.

The Role of Global Femoral Offset in Total Hip Arthroplasty with High Hip Center Technique.

OBJECTIVE: The high hip center (HHC) technique has been proposed for the treatment of patients with developmental dysplaisa of the hip (DDH) who have an acetabular bone defect. However, the importance of global femoral offset (FO) in the application of this technique has not been sufficiently appreciated. Our goals were to confirm that the HHC technique is feasible in the treatment of patients with DDH and to assess the function of global FO in this procedure. METHODS: We retrospectively analyzed 73 patients who underwent total hip arthroplasty using high hip center technique for unilateral DDH at our hospital between January 2014 and June 2019. According to global FO, the patients were split into three groups: increased FO group (increment greater than 5 mm), restored FO group (restoration within 5 mm) and decreased FO group (reduction greater than 5 mm). Patients' medical records and plain radiographs were reviewed. One-way ANOVA was used to compare radiographic outcomes and Harris hip score (HHS). Paired t-test was used to assess preoperative and postoperative HHS and leg length discrepancy. Trochanteric pain syndrome, Trendelenburg sign and postoperative limp was evaluated with Fisher's exact test. RESULTS: The average follow-up time was 7.5 ± 1.4 years. The patients' HHS and leg length discrepancy were significantly improved (p < 0.05). In terms of vertical acetabular height, abductor arm, postoperative leg length difference, and acetabular cup inclination, there was no statistically significant difference between the three groups. At the last follow-up, HHS was significantly higher in the restored FO group than in the decreased FO and increased FO groups. Trochanteric pain syndrome occurred in 15.0% and Trendelenburg sign and postoperative limp in 8.2% of all patients, respectively. Trochanteric pain syndrome, Trendelenburg sign and postoperative limp did not differ significantly across the three groups. One patient in increased FO group underwent revision for dislocation 6 years after surgery. CONCLUSION: The HHC technique is an alternative technique for total hip arthroplasty in patients with acetabular bone abnormalities, according to the results of the mid-term follow-up. Also, controlling the correction of the global femoral offset to within 5 mm may lead to better clinical outcomes.

Incidence and non-genetic risk factors of irinotecan-induced severe neutropenia in Chinese adult inpatients.

To analyze the incidence and nongenetic risk factors of irinotecan-induced severe neutropenia in the hospital, and provide additional reference and help for clinical treatment. A retrospective analysis of patients who received irinotecan based chemotherapy from May 2014 to May 2019 in Renmin Hospital of Wuhan University was conducted. Univariate analysis and binary logistic regression analysis with the forward stepwise method were used to assess the risk factors associated with severe neutropenia induced by irinotecan. Of the 1312 patients treated with irinotecan-based regmines, only 612 patients met the inclusion criteria, and 32 patients developed irinotecan-induced severe neutropenia. In the univariate analysis, variables associated with severe neutropenia were tumor type, tumor stage, and therapeutic regimen. In the multivariate analysis, irinotecan plus lobaplatin, lung cancer or ovarian cancer, tumor stage T2, T3, and T4, were identified as risk factors that contributed independently to irinotecan-induced severe neutropenia (P < .05), respectively. The results showed that the incidence of irinotecan-induced severe neutropenia was 5.23% in the hospital. The risk factors included tumor type (lung cancer or ovarian cancer), tumor stage (T2, T3, and T4) and therapeutic regimen (irinotecan plus lobaplatin). Therefore, for patients with these risk factors, it might be advisable to actively consider optimum management to reduce the occurrence of irinotecan-induced severe neutropenia.

Drug-induced liver injury in COVID-19 patients during hospitalization.

Since coronavirus disease 2019 (COVID-19) outbreaks in December 2019 in Wuhan, almost no studies have systematically described drug-induced liver injury (DILI) in COVID-19 patients. This study aimed to assess the characteristics of liver test abnormality or liver injury in patients with COVID-19, and further to explore DILI in COVID-19 patients during hospitalization. It was a single-center retrospective analysis of confirmed severe acute respiratory syndrome coronavirus 2 infected patients in the hospital from January 2020 to March 2020. Univariate and multivariate logistic regression analysis were used to assess the risk factors associated with liver test abnormality or liver injury. At admission, 148 (48.8%, 148/303) patients had abnormal liver test results and 7 (2.4%, 7/303) had liver injury, while 195 (64.4%, 195/303) had abnormal liver test results and 17 (5.6%, 17/303) had liver injury during hospitalization. After excluding these patients with liver disease and liver function abnormalities or liver injury at admission, 15 (11.1%, 15/135) patients developed DILI during hospitalization. Further regression analysis indicated that methylprednisolone (odds ratio = 4.177, 95% confidence interval [1.106-15.771], P = .035), but not Chinese herbal medicine or other used drug, was associated with DILI in patients during hospitalization. Abnormal liver function results were in more than half of patients with COVID-19, and the incidence of DILI in COVID-19 patients was 11.1% during hospitalization. Liver test abnormality or liver injury in patients might be directly caused by the viral infection at admission, but the detrimental effects on liver injury mainly related to certain medications used during hospitalization, particularly methylprednisolone. Severe COVID-19 could increase the occurrence of liver injury (P = .007) during hospitalization, but not a risk factor of liver injury. However, Chinese herbal medicine was a protective factor for liver injury.

Circular RNA CircSLC8A1 contributes to osteogenic differentiation in hBMSCs via CircSLC8A1/miR-144-3p/RUNX1 in periprosthetic osteolysis.

Circular RNAs (circRNAs) are often found in eukaryocyte and have a role in the pathogenesis of a variety of human disorders. Our related research has shown the differential expression of circRNAs in periprosthetic osteolysis (PPOL). However, the involvement of circRNAs in the exact process is yet unknown. CircSLC8A1 expression was evaluated in clinical samples and human bone marrow mesenchymal stem cells (hBMSCs) in this investigation using quantitative real-time PCR. In vitro and in vivo studies were conducted to explicate its functional role and pathway. We demonstrated CircSLC8A1 is involved in PPOL using gain- and loss-of-function methods. The association of CircSLC8A1 and miR-144-3p, along with miR-144-3p and RUNX1, was predicted using bioinformatics. RNA pull-down and luciferase assays confirmed it. The impact of CircSLC8A1 in the PPOL-mouse model was also investigated using adeno-associated virus. CircSLC8A1 was found to be downregulated in PPOL patients' periprosthetic tissues. Overexpression of CircSLC8A1 promoted osteogenic differentiation (OD) and inhibited apoptosis of hBMSCs in vitro. The osteogenic markers of RUNX1, osteopontin (OPN) and osteocalcin (OCN) were significantly upregulated in hBMSCs after miR-144-3p inhibitor was transferred. Mechanistic analysis demonstrated that CircSLC8A1 directly bound to miR-144-3p and participated in PPOL through the miR-144-3p/RUNX1 pathway in hBMSCs. Micro-CT and quantitative analysis showed that CircSLC8A1 markedly inhibited PPOL, and osteogenic markers (RUNX1, OPN and OCN) were significantly increased (P<0.05) in the mice model. Our findings prove that CircSLC8A1 exerted a regulatory role in promoting osteogenic differentiation in hBMSCs, and CircSLC8A1/miR-144-3p/RUNX1 pathway may provide a potential target for prevention of PPOL.

Material properties of degradable alloy Fe-30Mn-0.6N and its effect on ferroptosis in synoviocytes.

Ferroalloy has shown potential as implant materials, but little attention has been paid to their effects on synovial tissue ferroptosis. This study aimed to examine the mechanical properties, degradability and biocompatibility of Fe-30Mn-0.6N alloy and effects of it on synovial tissue ferroptosis. Tensile testing showed that Fe-30Mn-0.6N alloys exhibited tensile strength of 487 ± 18 MPa, yield strength of 221 ± 10 MPa, elongation of 16.9 ± 0.3% and Young's modulus of 37.7 ± 1.3 GPa. In vivo experiments, the cross-sectional area of the Fe-30Mn-0.6N alloys decreased by 73.32 ± 12.73% after 8 weeks of implantation. The results of scanning electron microscopy (SEM) and surface elemental analysis (EDS) showed that the Fe-30Mn-0.6N alloys had more Ca, O, C and P element deposition (p < .05). After 2, 4 and 8 weeks of implantation, no inflammatory response was observed in peri-implant synovial tissue of Fe-30Mn-0.6N and Ti-6Al-4V alloys, and Fe-30Mn-0.6N alloys did not affect the expression of the ferroptosis inhibitory gene Glutathione peroxidase 4 (GPX4). Compared with the control group, 30% Fe-30Mn-0.6N alloy extracts did not affect the cell viability (p > .05) in vitro, and intracellular Fe2+ and the reactive oxygen species (ROS) was significantly reduced (p < .05). WB and PCR results showed that the 30% extracts increased the protein activity and mRNA expression of GPX4, FTH1 and SLC7A11 in synoviocytes, but had no effect on PTGS2 and p53. It is concluded that Fe-30Mn-0.6N had degradability and biocompatibility in peri-implant synovial tissue, and did not induce significantly ferroptosis in synoviocytes.

Phytohormone profiles and related gene expressions after endodormancy release in developing Pinus tabuliformis male strobili.

Development after endo-dormancy release ensures perennial plants, such as forest trees, proper response to environmental changes and enhances their adaptability. In northern hemisphere, megasporophore and microsporophore of conifers undergo dormancy to complete their development. Here combined with transcriptome data, we used high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (ESI-HPLC-MS/MS) to quantitatively analyse the various hormones (Abscisic Acid (ABA), 3-Indoleacetic acid (IAA), Gibberellins (GAs), Cytokinin (CTK), Jasmonic acid (JA) and Salicylic acid (SA)) of Chinese pine (Pinus tabuliformis Carr.) male strobili after endo-dormancy release. More specifically, we analysed endogenous hormones and their related-genes and verified the important role of ABA in plants growth and development. We observed rapid decrease in ABA content after dormancy release, resulting in reducing the inhibitory effect on male strobili growth. Similarly, rapid drop in ABA/GA ratio was observed and was associated with the start of male strobili growth and development. Combined with transcriptome data, we found that HAB2-SnRK2.10 played a central role in the ABA pathway in the entire network of hormones regulating male strobili development. Due to external environment warming, the differentially expressed HAB2-SnRK gene led to ABA content rapid decline, thus initiating male strobili growth. We constructed a network of hormone-regulated development to understand the interactions between hormones after male strobili dormancy release of male strobili. This study provided essential foundations for studying megasporophore and microsporophore growth mechanism after endo-dormancy and offered new ideas for flower development in gymnosperms and angiosperms.

A highly sensitive method for simultaneous detection of hAAG and UDG activity based on multifunctional dsDNA probes mediated exponential rolling circle amplification.

DNA glycosylase is an indispensable DNA damage repair enzyme which can recognize and excise the damaged bases in the DNA base excision-repair pathway. The dysregulation of DNA glycosylase activity will give rise to the dysfunction of base excision-repair and lead to abnormalities and diseases. The simultaneous detection of multiple DNA glycosylases can help to fully understand the normal physiological functions of cells, and determine whether the cells are abnormal in pre-disease. Regrettably, the synchronous detection of functionally similar DNA glycosylases is a great challenge. Herein, we developed a multifunctional dsDNA probe mediated exponential rolling circle amplification (E-RCA) method for the simultaneously sensitive detection of human alkyladenine DNA glycosylase (hAAG) and uracil-DNA glycosylase (UDG). The multifunctional dsDNA probe contains the hypoxanthine sites and the uracil sites which can be recognized by hAAG and UDG respectively to generate apyrimidinic (AP) sites in the dsDNA probe. Then the AP sites will be recognized and cut by endonuclease Ⅳ (Endo IV) to release corresponding single-stranded primer probes. Subsequently, two padlock DNA templates are added to initiate E-RCA to generate multitudinous G-quadruplexes and/or double-stranded dumbbell lock structures, which can combine N-methyl mesoporphyrin IX (NMM) and SYBR Green Ⅰ (SGI) for the generation of respective fluorescent signals. The detection limits are obtained as low as 0.0002 U mL-1 and 0.00001 U mL-1 for hAAG and UDG, respectively. Notably, this method can realize the simultaneous detection of two DNA glycosylases without the use of specially labeled probes. Finally, this method is successfully applied to detect hAAG and UDG activities in the lysates of HeLa cells and Endo1617 cells at single-cell level, and to detect the inhibitors of DNA glycosylases.

A Chimeric Cationic Peptide Composed of Human ß-Defensin 3 and Human ß-Defensin 4 Exhibits Improved Antibacterial Activity and Salt Resistance.

Human beta-defensins (hBDs) play an important role in the host defense against various microbes, showing different levels of antibacterial activity and salt resistance in vitro. It is of interest to investigate whether can chimeric hBD analogs enhanced antibacterial activity and salt resistance. In this study, we designed a chimeric human defensin, named H4, by combining sequences of human beta-defensin-3 (hBD-3) and human beta-defensin-4 (hBD-4), then evaluated its antibacterial activity, salt resistance, and cytotoxic effects. The result showed that the antibacterial activity of H4 against most tested strains, including Klebsiella pneumonia, Enterococcus faecalis, Staphyloccocus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, and Acinetobacter baumannii was significantly improved compared to that of hBD-3 and hBD-4. Notably, H4 exhibited significantly better antibacterial activity against multidrug resistant isolate A. baumannii MDR-ZJ06 than commonly used antibiotics. Chimeric H4 still showed more than 80% antibacterial activity at high salt concentration (150 µM), which proves its good salt tolerance. The cytotoxic effect assay showed that the toxicity of H4 to Hela, Vero, A549 cells and erythrocytes at a low dose (<10 µg/ml) was similar to that of hBD-3 and hBD-4. In conclusion, given its broad spectrum of antibacterial activity and high salt resistance, chimeric H4 could serve as a promising template for new therapeutic antimicrobial agents.

Intracerebral Transplantation of Neural Stem Cells Restores Manganese-Induced Cognitive Deficits in Mice.

Manganese (Mn) is a potent neurotoxin known to cause long-lasting structural damage and progressive cognitive deficits in the brain. However, new therapeutic approaches are urgently needed since current treatments only target symptoms of Mn exposure. Recent studies have suggested a potential role for multipotent neural stem cells (NSCs) in the etiology of Mn-induced cognitive deficits. In this study, we evaluated the effect of direct intracerebral transplantation of NSCs on cognitive function of mice chronically exposed to MnCl2, and further explored the distribution of transplanted NSCs in brain tissues. NSCs were isolated and bilaterally injected into the hippocampal regions or lateral ventricles of Mn-exposed mice. The results showed that many transplanted cells migrated far away from the injection sites and survived in vivo in the Mn-exposed mouse brain, implying enhanced neurogenesis in the host brain. We found that NSCs transplanted into either the hippocampal regions or the lateral ventricles significantly improved spatial learning and memory function of the Mn-exposed mice in the Morris water maze. Immunofluorescence analyses indicated that some surviving NSCs differentiated into neurons or glial cells, which may have become functionally integrated into the impaired local circuits, providing a possible cellular basis for the improvement of cognitive function in NSC-transplanted mice. Taken together, our findings confirm the Mn-induced impairment of neurogenesis in the brain and underscore the potential of treating Mn exposure by NSC transplantation, providing a practical therapeutic strategy against this type of neurotoxicity.

1,2-Dimyristoyl-sn-glycero-3-phosphocholine promotes the adhesion of nanoparticles to bio-membranes and transport in rat brain.

1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) coated on the surface of superparamagnetic iron oxide nanoparticles (SPIONs) has advantages in neurotherapy and drug delivery. In this study, the surface of polyvinylpyrrolidone (PVP)-SPIONs was modified with DMPC, then PVP-SPIONs and DMPC/PVP-SPIONs were co-incubated with rat adrenal pheochromocytoma (PC-12) cells to observe the effect of DMPC on the distribution of SPIONs in cells, and further PVP-SPIONs and DMPC/PVP-SPIONs were implanted into the substantia nigra of Sprague-Dawley (SD) rats by stereotaxic injection, and the brain tissues were removed at both twenty-four hours and seven days after injection. The distribution and transport of nanoparticles in the substantia nigra in vivo were explored in these different time periods. The results show that DMPC/PVP-SPIONs were effectively distributed on the membranes of axons, as well as dendritic and myelin sheaths. The attachment of nanoparticles to bio-membranes in the brain could result from similar phospholipid structures of DMPC and the membranes. In addition, DMPC/PVP-SPIONs were transported in the brain faster than those without DMPC. In vitro experiments found that DMPC/PVP-SPIONs enter cells more easily. These characteristics of iron oxide nanoparticles that are modified by phospholipids lead to potential applications in drug delivery or activating neuron membrane channels.

Calreticulin enhances the secretory trafficking of a misfolded α-1-antitrypsin.

α1-antitrypsin (AAT) regulates the activity of multiple proteases in the lungs and liver. A mutant of AAT (E342K) called ATZ forms polymers that are present at only low levels in the serum and induce intracellular protein inclusions, causing lung emphysema and liver cirrhosis. An understanding of factors that can reduce the intracellular accumulation of ATZ is of great interest. We now show that calreticulin (CRT), an endoplasmic reticulum (ER) glycoprotein chaperone, promotes the secretory trafficking of ATZ, enhancing the media:cell ratio. This effect is more pronounced for ATZ than with AAT and is only partially dependent on the glycan-binding site of CRT, which is generally relevant to substrate recruitment and folding by CRT. The CRT-related chaperone calnexin does not enhance ATZ secretory trafficking, despite the higher cellular abundance of calnexin-ATZ complexes. CRT deficiency alters the distributions of ATZ-ER chaperone complexes, increasing ATZ-BiP binding and inclusion body formation and reducing ATZ interactions with components required for ER-Golgi trafficking, coincident with reduced levels of the protein transport protein Sec31A in CRT-deficient cells. These findings indicate a novel role for CRT in promoting the secretory trafficking of a protein that forms polymers and large intracellular inclusions. Inefficient secretory trafficking of ATZ in the absence of CRT is coincident with enhanced accumulation of ER-derived ATZ inclusion bodies. Further understanding of the factors that control the secretory trafficking of ATZ and their regulation by CRT could lead to new therapies for lung and liver diseases linked to AAT deficiency.

Attachment of streptavidin-modified superparamagnetic iron oxide nanoparticles to the PC-12 cell membrane.

Efficient attachment of magnetic nanoparticles to cell membranes plays an important role in the activation of cell membrane channels. Streptavidin (SA) was successfully modified to Poly (ethylene imine) (PEI)-superparamagnetic iron oxide nanoparticles (SPIONs) to form SA/PEI-SPIONs, which have high colloidal stability and low cytotoxicity. The SA/PEI-SPIONs were incubated with PC-12 cells which had first been cultured in a Roswell Park Memorial Institute medium 1640 containing 0.2 mg l-1 biotin for 12 h. The cells were observed by transmission electron microscopy, and the nanoparticles were clearly attached on the cell membrane, which can be attributed to the specific binding between the SA and biotin sites on the cell surface. This work provides a simple way to attach SA-modified nanoparticles on the membranes of cells by only culturing cells in a biotin-containing medium. This work makes possible biomedical applications that require nanoparticles to target cell membranes.

The synthesis and characterization of glutathione-modified superparamagnetic iron oxide nanoparticles and their distribution in rat brains after injection in substantia nigra.

Glutathione-modified superparamagnetic iron oxide nanoparticles (GSH-SPIONs) were prepared by conjugating glutathione (GSH) on the surface of the PEG (Polyethylene glycol)/PEI (polyethyleneimine)-SPIONs which were synthesized by thermal decomposition method. Thermogravimetric analysis showed that the mass fraction of GSH on the surface of SPIONs was 30.64 wt%. GSH-SPIONs in PBS were injected into the substantia nigra of rat brains. The subcellular distributions of the nanoparticles in the brains was examined by the transmission electron microscope (TEM). A remarkable amount of GSH-SPIONs were found in vesicles inside cell bodies and axons, and in mitochondria. TEM pictures show that GSH-SPIONs enter the neuronal cells by endocytosis and travel through axoplasmic transport. GSH-SPIONs have great potential as drug delivery agents in the brain to treat diseases or study brain function via mitochondria-targeting way or axoplasmic transport way.

Superparamagnetic Iron Oxide Nanoparticles Modified with Tween 80 Pass through the Intact Blood-Brain Barrier in Rats under Magnetic Field.

The methods for the delivery of theranostic agents across the blood-brain barrier (BBB) are highly required. Superparamagnetic iron oxide nanoparticles (SPIONs) coated with PEG (poly(ethylene glycol)), PEI (poly(ethylene imine)), and Tween 80 (polysorbate 80) (Tween-SPIONs) were prepared. We demonstrate the effective passage of tail-vein-injected Tween-SPIONs across normal BBB in rats under an external magnetic field (EMF). The quantitative analyses show significant accumulation of SPIONs in the cortex near the magnet, with progressively lower accumulation in brain tissues far from the magnet. A transmission electron microscopy picture of an ultrathin section of the rat brain displays Tween-SPIONs crossing the BBB. The comparative study confirms that both the Tween-80 modification and EMF play crucial roles in the effective passage of SPIONs across the intact BBB. However, the magnetic force alone cannot drag the SPIONs coated with PEI/PEG polymers through the BBB. The results indicate the Tween-SPIONs cross the BBB via an active penetration facilitated by EMF. This work is encouraging for further study on the delivery of drug or diagnostic agents into the parenchyma of the brain for dealing with neurological disorders by using Tween-SPIONs carriers under EMF.

[Effects of polygala on the neurogenesis of manganese poisoned mice].

OBJECTIVE: To investigate the effects of polygala on leaning and memory and the expression of Microtubule associated protein on manganese poisoned mice. METHODS: 60 female Kunming mice were randomly and equally divided into 5 group. They are normal control group (CG), manganese poisoned group (MG), manganese poisoned with polygala high dose group (MHG), manganese poisoned with polygala middle dose group (MMG), manganese poisoned with polygala low dose group (MLG). The model of manganese poisoned mice was prepared of the way of intraperitoneal injection of manganese chloride (MnCl2 15 mg/kg), the spatial learning and memory ability was tested by Morris water maze, the Doublecortin (DCX) was tested by the way of immunofluorescent staining in the SVZ and SGZ. RESULT: In the navigation test, compared with MG, the escape latency of MHG, MMG and MLG were significantly decreased (P < 0.05), in space exploration experiments, MHG, MMG, MLG compared with MG, the number increased significantly across platforms (P < 0.05). compared with MG, the DCX expression of MHG, MMG and MLG were significantly increased (P < 0.05). CONCLUTION: The leaning and memory ability of manganese poisoned mice can be improved by the polygala, and the mechanism may be related to promote the expression of DCX and neurogenesis in the brain.

[Effects of enriched environment and impoverished environment on learning and memory ability of manganese-exposed mice].

OBJECTIVE: To investigate the effects of enriched environment and impoverished environment on the learning and memory ability of manganese-exposed mice and the mechanism. METHODS: Forty female Kunming mice were randomly and equally divided into 4 group: control group (CG), standard environment and manganese exposure group (SEG), enriched environment and manganese exposure group (EEG), and impoverished environment and manganese exposure group (IEG). The mouse model of manganese poisoning was established by intraperitoneal injection of manganese chloride. The learning and memory ability was tested by Morris water maze. The expression of cAMP response element-binding protein (CREB) in area CA1 of the hippocampus was measured by immunohistochemistry. RESULTS: In place navigation test, the SEG had a significantly longer escape latency than the CG (P < 0.05), and the EEG had a significantly shorter escape latency than the SEG (P < 0.05); there was no significant difference in escape latency between IEG and SEG (P > 0.05). In spatial probe test, the EEG had a significantly greater number of platform crossings than the SEG (P < 0.05), and the IEG had a significantly smaller number of platform crossings than the SEG (P < 0.05). The expression of CREB in area CA1 of the hippocampus was significantly lower in IEG and SEG than in CG (P < 0.05), and it was significantly higher in EEG than in SEG (P < 0.05). CONCLUSION: In the enriched environment, the learning and memory ability of manganese-exposed mice can be improved, which may be due to the increased expression of CREB in the hippocampus.

[Effect of Lycium barbarum polysaccharides on neurogenesis and learning & memory in manganese poisoning mice].

OBJECTIVE: To study the effect of Lycium barbarum polysaccharides (LBP) on neurogenesis and learning & memory of manganese poisoning mice. METHODS: Healthy adult Kunming mice were divided into 5 groups, the control group (A), the manganese poisoning (by manganese chloride peritoneal injection) group (B), the manganese poisoning and treated with gastric perfusion of high, medium, low dosage LBP groups (C, D and E). The spatial learning & memory capacity of mouse was determined by Morris water maze training test. The neurogenetic cells were labelled with bromodeoxyuridine (BrdU) and detected by immunohistochemistry. RESULTS: The average escape latency was significantly higher and the times of passing through platform lower in group B than those in group A (P<0.05). BrdU positive cells in groups C, D and E were significantly more than those in group B (P<0.05). CONCLUSION: LBP could enhance the learning & memory capability of the manganese poisoning mice by promoting neurogenesis in hippocampus.

[Effects of manganismus on proliferation of neural stem cells in mice's hippocampus].

OBJECTIVE: To explore the effects of manganese poisoning on the proliferation of neural stem cells (NSCs) in mice's hippocampus. METHODS: The mice (weight 8 approximately 10 g) were divided into control group(CG) low-dose group(LDG) middle-dose group(MDG) and high-dose group(HDG)by intraperitoneal injection of 0, 5, 20, 50 mg x kg(-1) x d(-1) of manganese chloride dissolved in physiological saline. The ability of learning and memory was detected by Morris Water Maze, and the proliferation of NSCs in subgranular zone (SGZ) in these mice's hippocampus was also detected by immunohistochemistry. RESULTS: 1) Compared with the CG, the ability of learning and memory in all manganism group decreased significantly (P < 0.01) and this phenomenon in HDG was most notable (P < 0.01). Meanwhile, the ability of memory was negatively correlated with the dose of manganese chloride (r(s) = -0.598, P < 0.01), but the difference of swimming speed in every group was of no statistic significance. (2) The numbers of NSCs in proliferation period in SGZ of all manganism groups was much lower than that of CG (P < 0.01) negatively correlated with the dose of manganese chloride (r(s) = -0.666, P < 0.01). (3) The reduction of NSCs had a positive correlation to the depression of learning and memory (r(s) = 0.734, P < 0.01). CONCLUSIONS: Manganismus can affect the ability of learning and memory, which is probably caused by the inhalation of manganese on NSCs in hippocampus.

Antinociceptive effects of galanin in the rat tuberomammillary nucleus and the plasticity of galanin receptor 1 during hyperalgesia.

Although the tuberomammillary nucleus (TM) is well defined in terms of anatomy and neurochemistry, little is known about its function in nociceptive modulation. There was an abundance of galanin-immunoreactive fibers in the TM, and galanin has been implicated in pain processing. The present study assessed the role of galanin in the modulation of nociception in the TM of rats. Intra-TM injection of galanin dose-dependently increased the hindpaw withdrawal latency of rats to a noxious thermal stimulus, indicating an antinociceptive role of galanin in the TM. The antinociceptive effect of galanin was blocked by a subsequent intra-TM injection of galantide, a putative galanin receptor antagonist, suggesting that the antinociceptive effect of galanin is mediated by galanin receptors. Moreover, there was abundant galanin receptor 1 (GalR1) in the TM, and the number of GalR1-positive neurons in the ipsilateral TM increased significantly after unilateral loose ligation of the sciatic nerve compared with the contralateral TM or the TM of intact rats. However, the number of GalR1-positive neurons was not significantly altered by carrageenan-induced inflammation, in either the ipsilateral or the contralateral TM. The results suggest that galanin and GalR1 in the TM may play important roles in pain regulation.