Chronic Lead Exposure in Adult Mice: Associations with miR-671/CDR1as Regulation, NF-κB Signaling, and Alzheimer's Disease-like Pathology.

Long-term exposure to lead (Pb) can result in chronic damage to the body through accumulation in the central nervous system (CNS) leading to neurodegenerative diseases, such as Alzheimer's disease (AD). This study delves into the intricate role of miR-671/CDR1as regulation in the etiology of AD-like lesions triggered by chronic Pb exposure in adult mice. To emulate the chronic effects of Pb, we established a rodent model spanning 10 months of controlled Pb administration, dividing 52 C57BL/6J mice into groups receiving varying concentrations of Pb (1, 2, or 4 g/L) alongside an unexposed control. Blood Pb levels were monitored using serum samples to ensure accurate dosing and to correlate with observed toxicological outcomes. Utilizing the Morris water maze, a robust behavioral assay for assessing cognitive functions, we documented a dose-dependent decline in learning and memory capabilities among the Pb-exposed mice. Histopathological examination of the hippocampal tissue revealed tell-tale signs of AD-like neurodegeneration, characterized by the accumulation of amyloid plaques and neurofibrillary tangles. At the molecular level, a significant upregulation of AD-associated genes, namely amyloid precursor protein (APP), ß-secretase 1 (BACE1), and tau, was observed in the hippocampal tissue of Pb-exposed mice. This was accompanied by a corresponding surge in the protein levels of APP, BACE1, amyloid-ß (Aß), and phosphorylated tau (p-tau), further implicating Pb in the dysregulation of these key AD markers. The expression of CDR1as, a long non-coding RNA implicated in AD pathogenesis, was found to be suppressed in Pb-exposed mice. This observation suggests a potential mechanistic link between Pb-induced neurotoxicity and the dysregulation of the CDR1as/miR-671 axis, which warrants further investigation. Moreover, our study identified a dose-dependent alteration in the intracellular and extracellular levels of the transcription factor nuclear factor-kappa B (NF-κB). This finding implicates Pb in the modulation of NF-κB signaling, a pathway that plays a pivotal role in neuroinflammation and neurodegeneration. In conclusion, our findings underscored the deleterious effects of Pb exposure on the CNS, leading to the development of AD-like pathology. The observed modulation of NF-κB signaling and miR-671/CDR1as regulation provides a plausible mechanistic framework for understanding the neurotoxic effects of Pb and its potential contribution to AD pathogenesis.

Hidden blood loss and the influential factors after minimally invasive treatment of posterior pelvic ring injury with sacroiliac screw.

BACKGROUND: To analyze the perioperative bleeding and hidden blood loss (HBL) of sacroiliac screw minimally invasive treatment of pelvic posterior ring injury and explore the influential factors of HBL after operation for providing reference for clinical treatment. METHOD: A retrospective analysis was conducted on data from 369 patients with posterior pelvic ring injuries treated with sacroiliac screws internal fixation at our hospital from January 2015 to January 2022. The research was registered in the Chinese Clinical Trial Registry in July 2022 (ChiCTR2200061866). The total blood loss (TBL) and HBL of patients were counted, and the factors such as gender, age, and surgical duration were statistically analyzed. The influential factors of HBL were analyzed by multiple linear regression. RESULTS: The TBL was 417.96 ± 98.05 ml, of which the visible blood loss (VBL) was 37.00 ± 9.0 ml and the HBL was 380.96 ± 68.8 ml. The HBL accounted for 91.14 ± 7.36% of the TBL. Gender, surgical duration, fixed position, and fixed depth had significant effects on the HBL (P < 0.05). CONCLUSIONS: The HBL was the main cause of anemia after minimally invasive treatment of posterior pelvic ring injury with a sacroiliac screw. Gender, surgical duration, fixed position, and fixed depth were closely related to the occurrence of HBL. In clinical treatment, we should consider these influential factors and take effective measures to reduce the impact of HBL on patients.

Genome-Wide CRISPR Screen Identifies an NF2-Adherens Junction Mechanistic Dependency for Cardiac Lineage.

BACKGROUND: Cardiomyocyte differentiation involves a stepwise clearance of repressors and fate-restricting regulators through the modulation of BMP (bone morphogenic protein)/Wnt-signaling pathways. However, the mechanisms and how regulatory roadblocks are removed with specific developmental signaling pathways remain unclear. METHODS: We conducted a genome-wide CRISPR screen to uncover essential regulators of cardiomyocyte specification in human embryonic stem cells using a myosin heavy chain 6 (MYH6)-GFP (green fluorescence protein) reporter system. After an independent secondary single guide ribonucleic acid validation of 25 candidates, we identified NF2 (neurofibromin 2), a moesin-ezrin-radixin like (MERLIN) tumor suppressor, as an upstream driver of early cardiomyocyte lineage specification. Independent monoclonal NF2 knockouts were generated using CRISPR-Cas9, and cell states were inferred through bulk RNA sequencing and protein expression analysis across differentiation time points. Terminal lineage differentiation was assessed by using an in vitro 2-dimensional-micropatterned gastruloid model, trilineage differentiation, and cardiomyocyte differentiation. Protein interaction and post-translation modification of NF2 with its interacting partners were assessed using site-directed mutagenesis, coimmunoprecipitation, and proximity ligation assays. RESULTS: Transcriptional regulation and trajectory inference from NF2-null cells reveal the loss of cardiomyocyte identity and the acquisition of nonmesodermal identity. Sustained elevation of early mesoderm lineage repressor SOX2 and upregulation of late anticardiac regulators CDX2 and MSX1 in NF2 knockout cells reflect a necessary role for NF2 in removing regulatory roadblocks. Furthermore, we found that NF2 and AMOT (angiomotin) cooperatively bind to YAP (yes-associated protein) during mesendoderm formation, thereby preventing YAP activation, independent of canonical MST (mammalian sterile 20-like serine-threonine protein kinase)-LATS (large tumor suppressor serine-threonine protein kinase) signaling. Mechanistically, cardiomyocyte lineage identity was rescued by wild-type and NF2 serine-518 phosphomutants, but not NF2 FERM (ezrin-radixin-meosin homology protein) domain blue-box mutants, demonstrating that the critical FERM domain-dependent formation of the AMOT-NF2-YAP scaffold complex at the adherens junction is required for early cardiomyocyte lineage differentiation. CONCLUSIONS: These results provide mechanistic insight into the essential role of NF2 during early epithelial-mesenchymal transition by sequestering the repressive effect of YAP and relieving regulatory roadblocks en route to cardiomyocytes.

[Progress on treatment of acetabular quadrilateral plate injury].

Acetabular quadrilateral plate injury has become a hot spot and focus in the field of orthopaedic trauma and pelvic floor function in recent years. Although there are five fracture types,they are all based on fracture morphology,without considering the pulling force of ligaments,joint capsular and muscles. A perfect classification needs to describe the displacement of bone mass in three-dimensional space to better guide reduction and fixation. The seven incision and exposure methods are still the traditional open-eye surgery,and how to protect the criss-crossing vascular neural network and pelvic organs is still the focus. Quadrilateral defect causes dislocation of artificial hip joint,and quantitative evaluation of quadrilateral defect volume and revision techniques are still a hot topic. In this paper,the viewpoints of three-dimensional network structure of acetabular pelvic vascular anatomy,anatomical surgical target channel and fixation anchor point of acetabular fracture reduction are proposed to design new techniques for accurate and minimally invasive surgical operations,in order to realize the requirements of rapid orthopedic rehabilitation.

Deleterious Mechanical Deformation Selects Mechanoresilient Cancer Cells with Enhanced Proliferation and Chemoresistance.

Cancer cells in secondary tumors are found to form metastases more efficiently as compared to their primary tumor counterparts. This is partially due to the unfavorable microenvironments encountered by metastasizing cancer cells that result in the survival of a more metastatic phenotype from the original population. However, the role of deleterious mechanical stresses in this change of metastatic potential is unclear. Here, by forcing cancer cells to flow through small capillary-sized constrictions, it is demonstrated that mechanical deformation can select a tumor cell subpopulation that exhibits resilience to mechanical squeezing-induced cell death. Transcriptomic profiling reveals up-regulated proliferation and DNA damage response pathways in this subpopulation, which are further translated into a more proliferative and chemotherapy-resistant phenotype. These results highlight a potential link between the microenvironmental physical stresses and the enhanced malignancy of metastasizing cancer cells which may be utilized as a therapeutic strategy in preventing the metastatic spread of cancer cells.

Current status of robot-assisted surgery in the clinical application of trauma orthopedics in China: A systematic review.

Background and Aims: To elaborate on the development and characteristics of trauma orthopedic robots and their real curative effect in a clinical application through the collection and analysis of relevant literature and reported clinical results. Method: We conducted the Embase, ScienceDirect, Pubmed, Medline, Wanfang, CNKI, and VIP search of the literature on robotic-assisted surgery in trauma orthopedics in China. We combined search terms with "robotic surgery/artificial intelligence surgery/navigation surgery," "trauma/trauma orthopedics," and "China/Chinese." The exclusion criteria were: (1) articles in languages other than English or Chinese, (2) articles focused on other topics other than robotic-assisted surgery in trauma orthopedics of China, (3) article types were not clinical studies (reviews, basic research, etc.), and (4) articles were not included in the Chinese core journals or science citation index. Authors, type of surgery, robot type, and clinical research results were recorded and analyzed. Results: There were three categories of surgical robots in the clinical application of trauma orthopedics (TiRobot, electromagnetic navigation surgical robots, and small medical robots developed by Beijing Jishuitan Hospital). In terms of blood loss, the fluoroscopy time, and fluoroscopy frequency, most studies found that the robot group was significantly better than the traditional group. Conclusions: Robot-assisted surgery has obvious advantages in accuracy, stability, and reducing intraoperative radiation exposure, but there is no final conclusion about functional recovery.

BNIP-2 Activation of Cellular Contractility Inactivates YAP for H9c2 Cardiomyoblast Differentiation.

Rho GTPases and Hippo kinases are key regulators of cardiomyoblast differentiation. However, how these signaling axes are coordinated spatiotemporally remains unclear. Here, the central and multifaceted roles of the BCH domain containing protein, BNIP-2, in orchestrating the expression of two key cardiac genes (cardiac troponin T [cTnT] and cardiac myosin light chain [Myl2]) in H9c2 and human embryonic stem cell-derived cardiomyocytes are delineated. This study shows that BNIP-2 mRNA and protein expression increase with the onset of cTnT and Myl2 and promote the alignment of H9c2 cardiomyocytes. Mechanistically, BNIP-2 is required for the inactivation of YAP through YAP phosphorylation and its cytosolic retention. Turbo-ID proximity labeling corroborated by super-resolution analyses and biochemical pulldown data reveals a scaffolding role of BNIP-2 for LATS1 to phosphorylate and inactivate YAP in a process that requires BNIP-2 activation of cellular contractility. The findings identify BNIP-2 as a pivotal signaling scaffold that spatiotemporally integrates RhoA/Myosin II and LATS1/YAP mechanotransduction signaling to drive cardiomyoblast differentiation, by switching the genetic programming from YAP-dependent growth to YAP-silenced differentiation. These findings offer insights into the importance of scaffolding proteins in bridging the gap between mechanical and biochemical signals in cell growth and differentiation and the prospects in translational applications.

Acrylamide-induced damage to postsynaptic plasticity is CYP2E1 dependent in an SH-SY5Y co-culture system.

Acrylamide (ACR), a neurotoxic substance, is characterized by a range of industrial and population exposures. The effects of ACR on synapses have been examined, but the regulation and molecular mechanism of key proteins related to ACR and its metabolite glycidamide (GA) have not been elucidated. In this study, we constructed two co-culture systems to mimic neurons that do not express and overexpress CYP2E1. In these co-cultures, we observed the effects and relative influence of ACR and GA on cell survival as well as synaptic structural and functional plasticity. Next, we investigated the relationship between ACR-induced nerve damage and key proteins in the postsynaptic membrane. After ACR exposure, cell death and synaptic damage were significantly worse in CYP2E1-overexpressing co-culture systems, suggesting that ACR-induced neurotoxicity may be related to metabolic efficiency (including CYP2E1 activity). Moreover, with increasing doses of ACR, the key postsynaptic membrane proteins PSD-95 expression was reduced and CaMKII and NMDAR-2B phosphorylation was increased. ACR exposure also triggered a rapid dose- and time-dependent increase in intracellular Ca2+, whose changes can affect the expression of the above-mentioned key proteins. In summary, we clarified the relationship between ACR exposure, neuronal damage and postsynaptic plasticity and proposed an ACR-CYP2E1-GA: Ca2+-PSD-95-NMDAR-Ca2+-CaMKII effect chain. This information will further improve the development of an alternative pathway strategy for investigating the risk posed by ACR.

Identification of key pathways and genes in the progression of silicosis based on WGCNA.

Silicosis, induced by inhaling silica particles in workplaces, is one of the most common occupational diseases. The prognosis of silicosis and its consequent fibrosis is extremely poor due to limited treatment modalities and lack of understanding of the disease mechanisms. In this study, a Wistar rat model for silicosis fibrosis was established by intratracheal instillation of silica (0, 50, 100 and 200 mg/mL, 1 mL) with the evidence of Hematoxylin and Eosin (HE) and Masson staining and the expressions of inflammatory and fibrotic proteins of rats' lung tissues. RNA of lung tissues of rats exposed to 200 mg/mL silica particles and normal saline for 14 d and 28 d was extracted and sequenced to detect differentially expressed genes (DEGs) and to identify silicosis fibrosis-associated modules and hub genes by Weighted gene co-expression network analysis (WGCNA). Predictions of gene functions and signaling pathways were conducted using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. In this study, it has been demonstrated the promising role of the Hippo signaling pathway in silicosis fibrosis, which will be conducive to elucidating the specific mechanism of pulmonary fibrosis induced by silica and to determining molecular initiating event (MIE) and adverse outcome pathway (AOP) of silicosis fibrosis.

Lung Cancer Induces NK Cell Contractility and Cytotoxicity Through Transcription Factor Nuclear Localization.

Actomyosin-mediated cellular contractility is highly conserved for mechanotransduction and signalling. While this phenomenon has been observed in adherent cell models, whether/how contractile forces regulate the function of suspension cells like natural killer (NK) cells during cancer surveillance, is unknown. Here, we demonstrated in coculture settings that the evolutionarily conserved NK cell transcription factor, Eomes, undergoes nuclear shuttling during lung cancer cell surveillance. Biophysical and biochemical analyses revealed mechanistic enhancement of NK cell actomyosin-mediated contractility, which is associated with nuclear flattening, thus enabling nuclear entry of Eomes associated with enhanced NK cytotoxicity. We found that NK cells responded to the presumed immunosuppressive TGFß in the NK-lung cancer coculture medium to sustain its intracellular contractility through myosin light chain phosphorylation, thereby promoting Eomes nuclear localization. Therefore, our results demonstrate that lung cancer cells provoke NK cell contractility as an early phase activation mechanism and that Eomes is a plausible mechano-responsive protein for increased NK cytotoxicity. There is scope for strategic application of actomyosin-mediated contractility modulating drugs ex vivo, to reinvigorate NK cells prior to adoptive cancer immunotherapy in vivo (177 words).

Biomarkers of exposure and effect in the serum and urine of rats or workers exposed to 1-bromopropane.

Extensively used in several industries in China as a cleaning agent, 1-bromopropane (1-BP) has significant adverse effects on the central nervous system. However, neither its mechanism of action nor sensitive biomarkers related to it have been determined thus far. In this study, animal experiments and occupational surveys were performed to explore the typical exposure and effect biomarkers of neurotoxicity induced by 1-BP. Male Wistar rats were exposed to 0, 500, or 1000 ppm of 1-BP followed by pathological and biomarker analyses. An epidemiological survey was conducted on 71 workers each from 1-BP exposed and control groups. Serum and urine samples were collected for biomarker testing. cNSE represents neuron-specific enolase (NSE) in the cerebral cortex, where as sNSE represents NSE in the serum; similar terminology applies to S-100ß, and cyclooxygenase-2 (COX-2). In rats exposed to 1000 ppm 1-BP, pathological changes were observed in Purkinje cells, lumbar gray matter, and tibiofibular nerve, while levels of cNSE, cS-100ß, cCOX-2, sS-100ß, and sCOX-2 were significantly elevated at different time checkpoints. In the 500 ppm group, cCOX-2, sNSE, and sCOX-2 levels were significantly elevated at different time checkpoints. 1-BP and N-acetyl-S-(n-propyl)-L-cysteine (AcPrCys) were detected in rat urine, and there was a correlation between the level of sNSE or sCOX-2 and AcPrCys in the 500 ppm group. In the occupational epidemiological study, a significant correlation between AcPrCys and exposure concentration was also detected. The findings of this study indicated that AcPrCys was a sensitive exposure biomarker of 1-BP in rats as well as occupational populations.

A novel anatomical self-locking plate fixation for both-column acetabular fractures.

PURPOSE: To compare the stability of the posterior anatomic self-locking plate (PASP) with two types of popular reconstruction plate fixation, i.e. double reconstruction plate (DRP) and cross reconstruction plate (CRP), and to explore the influence of sitting and turning right/left on implants. METHODS: PASP, DRP and CRP were assembled on a finite element model of both-column fractures of the left acetabulum. A load of 600 N and a torque of 8 N·m were loaded on the S1 vertebral body to detect the change of stress and displacement when sitting and turning right/left. RESULTS: The peak stress and displacement of the three kinds of fixation methods under all loading conditions were CRP > DRP > PASP. The peak stress and displacement of PASP are 313.5 MPa and 1.15 mm respectively when turning right; and the minimal was 234.0 Mpa and 0.619 mm when turning left. CONCLUSION: PASP can provide higher stability than DRP and CRP for both-column acetabular fractures. The rational movement after posterior DRP and PASP fixation for acetabular fracture is to turn to the ipsilateral side, which can avoid implant failure.

A Promising transwell co-culture cell model for silicosis.

Silicosis, one of the most ancient occupational diseases, has not been elucidated and addressed until now. Although some medicines were partly effective in the clinical treatment and certain plausible mechanisms were partially ascertained, it is still urgent and necessary to explore its real and specific pathogenesis. With the development of the cell co-culture technique, the transwell co-culture system has been applied in several scientific fields, which is able to simulate the pathogenic process in vivo to the largest extent. In this sense, a transwell co-culture cell model for silicosis including RFL-6 (lung fibroblasts of rats), RLE-6TN (type II alveolar epithelial cells of rats) and NR8383 (alveolar macrophages of rats) cells was successfully established and the developmental process of silicosis in this model could be roughly divided into three stages: inflammatory stage, progressive stage and fibrotic stage, as evidenced by the morphological features and the inflammatory cytokines and fibrotic proteins of supernatants and the cells in this system. Results of this project will pave the way for clarifying the mechanism of silicosis and building a practical platform for the further exploration of molecular initiating event (MIE) and adverse outcome pathway (AOP) of silicosis.

Brain-derived neurotrophic factor protects against acrylamide-induced neuronal and synaptic injury via the TrkB-MAPK-Erk1/2 pathway.

Acrylamide has been shown to be neurotoxic. Brain-derived neurotrophic factor (BDNF) can alleviate acrylamide-induced synaptic injury; however, the underlying mechanism remains unclear. In this study, dibutyryl-cyclic adenosine monophosphate-induced mature human neuroblastoma (NB-1) cells were exposed with 0-100 µg/mL acrylamide for 24-72 hours. Acrylamide decreased cell viability and destroyed synapses. Exposure of co-cultured NB-1 cells and Schwann cells to 0-100 µg/mL acrylamide for 48 hours resulted in upregulated expression of synapsin I and BDNF, suggesting that Schwann cells can activate self-protection of neurons. Under co-culture conditions, activation of the downstream TrkB-MAPK-Erk1/2 pathway strengthened the protective effect. Exogenous BDNF can increase expression of TrkB, Erk1/2, and synapsin I, while exogenous BDNF or the TrkB inhibitor K252a could inhibit these changes. Taken together, Schwann cells may act through the BDNF-TrkB-MAPK-Erk1/2 signaling pathway, indicating that BDNF plays an important role in this process. Therefore, exogenous BDNF may be an effective treatment strategy for acrylamide-induced nerve injury. This study was approved by the Laboratory Animal Welfare and Ethics Committee of the National Institute of Occupational Health and Poison Control, a division of the Chinese Center for Disease Control and Prevention (approval No. EAWE-2017-008) on May 29, 2017.

BNIP-2 retards breast cancer cell migration by coupling microtubule-mediated GEF-H1 and RhoA activation.

Microtubules display dynamic turnover during cell migration, leading to cell contractility and focal adhesion maturation regulated by Rho guanosine triphosphatase activity. This interplay between microtubules and actomyosin is mediated by guanine nucleotide exchange factor (GEF)-H1 released after microtubule depolymerization or microtubule disconnection from focal adhesions. However, how GEF-H1 activates Rho upon microtubule disassembly remains elusive. Here, we found that BNIP-2, a BCH domain-containing protein that binds both RhoA and GEF-H1 and traffics with kinesin-1 on microtubules, is important for GEF-H1-driven RhoA activation upon microtubule disassembly. Depletion of BNIP-2 in MDA-MB-231 breast cancer cells decreases RhoA activity and promotes cell migration. Upon nocodazole-induced microtubule disassembly, the interaction between BNIP-2 and GEF-H1 increases, while knockdown of BNIP-2 reduces RhoA activation and cell rounding via uncoupling RhoA-GEF-H1 interaction. Together, these findings revealed that BNIP-2 couples microtubules and focal adhesions via scaffolding GEF-H1 and RhoA, fine-tuning RhoA activity and cell migration.

Layer dependence of the photoelectrochemical performance of a WSe2 photocathode characterized using in situ microscale measurements.

Transition-metal dichalcogenide (TMD) materials are good candidates for photoelectrochemical (PEC) electrode materials because of their distinctive optoelectronic properties and catalytic activities. Monolayer WSe2 is a p-type semiconductor with a direct bandgap that makes it a suitable PEC cathode material. In the present work, in situ PEC characterization of a single sheet device was carried out at the microscale to explore its performance. The PEC characteristics were found to be strongly related to the number of WSe2 layers. Monolayer WSe2 exhibited a dominant large current density and incident photo-to-current efficiency (IPCE) compared with those of multilayer WSe2. Its PEC performance decreased with increasing number of layers. The photocurrent mapping results also revealed that the basal-plane sites and the edge sites on a monolayer WSe2 sheet contributed equally to its catalytic activity, which is not consistent with traditional catalyst theory. The underlying mechanism is discussed.

Enhanced Performance of a Monolayer MoS2/WSe2 Heterojunction as a Photoelectrochemical Cathode.

Transition-metal dichalcogenide (TMD) semiconductors have attracted interest as photoelectrochemical (PEC) electrodes due to their novel band-gap structures, optoelectronic properties, and photocatalytic activities. However, the photo-harvesting efficiency still requires improvement. In this study, A TMD stacked heterojunction structure was adopted to further enhance the performance of the PEC cathode. A P-type WSe2 and an N-type MoS2 monolayer were stacked layer-by-layer to build a ultrathin vertical heterojunction using a micro-fabrication method. In situ measurement was employed to characterize the intrinsic PEC performance on a single-sheet heterostructure. Benefitting from its built-in electric field and type II band alignment, the MoS2/WSe2 bilayer heterojunction exhibited exceptional photocatalytic activity and a high incident photo-to-current conversion efficiency (IPCE). Comparing with the monolayer WSe2 cathode, the PEC current and the IPCE of the bilayer heterojunction increased by a factor of 5.6 and enhanced 50%, respectively. The intriguing performance renders the MoS2/WSe2 heterojunction attractive for application in high-performance PEC water splitting.

[Renal damage of indium sulfate on rats].

OBJECTIVE: To study the renal damage of indium sulfate. METHODS: 32 healthy Wistar rats were randomly and equally divided into 3 dose groups( 52. 3 mg/kg、104. 6 mg/kg 261. 4 mg/kg) and one negative control group. Indium sulfate were orally given once a day successively 5 days a week for 8 weeks. Each group of rats was collected24 hour urine after the end of the posion. We tested the content of Cr, BUN, T-AOC, ALB in serum and the GSH activity in kidney by kids and detected the ß2-MG content in serum and urine by ELISA test. Inductively coupled plasma mass spectrometry( ICP-MS)method was used to detect the content of indium in whole blood, urine and kidney tissue of rats. Hematoxylin and eosin( H&E) staining was used to detect histological changes. RESULTS: During the experiment, all the rats were normal in activities, feed and drinking water, and they developed stably. In the period of seventh weeks and eighth weeks, the body weight of rats in high dose group was significantly lower than the control group( P <0. 05). Compared with the control group[( 1. 27 ± 0. 55), ( 0. 40 ± 0. 01) and( 0. 30 ±0. 06) µg/L], 3 dose group of indium in blood[( 44. 10 ± 23. 10), ( 52. 08 ± 21. 03) and( 67. 42 ± 45. 98) µg/L], urine[( 0. 72 ± 0. 13), ( 2. 75 ± 0. 15) and( 4. 31 ± 0. 33)µg/L]and kidney [( 1. 36 ± 0. 83), ( 1. 52 ± 0. 49) and( 2. 87 ± 0. 20) µg/L] were significantly increased( P < 0. 05). The level of Cr in serum in the high dose group were significantly higher than that in the control group [( 66. 06 ± 18. 62) and( 46. 53 ± 7. 95)µmol/L, P < 0. 05], the serum BUN content[( 3. 98 ± 0. 82) and( 4. 09 ± 0. 71) mmol/L] in the high dose group and middle dose group were significantly lower than the control group [( 4. 77 ± 0. 49) mmol/L, P < 0. 05]. Compared with the control group, 3 dose group of the ß2-MG in serum and urine were significantly increased( P < 0. 05), and the level of T-AOC[( 4. 87 ± 2. 36), ( 4. 50 ± 2. 33) and( 4. 00 ± 3. 29) U/m L] in serum and GSH[( 6. 41 ± 1. 86), ( 5. 06 ± 2. 09) and( 2. 77 ± 2. 64) µmol/( g prot) ] in renal tissue were significantly decreased[( 15. 20 ± 5. 43) U/m L and( 14. 74 ± 6. 47) µmol/( g prot), P < 0. 05]. Compared with the control group, the middle and high dose exposure group had significant inflammatory pathological changes, mainly manifested as glomerular swelling, renal tubular structure abnormalities and inflammatory cell infiltration. CONCLUSION: Indium sulfate can cause the accumulation of indium in the kidney, oxidative damage, pathological changes and dysfunction in the kidney of rats.

Schwann cells protect against CaMKII- and PKA-dependent Acrylamide-induced Synapsin I phosphorylation.

OBJECTIVES: To explore the effects of Acrylamide (ACR), as well as the influence of Schwann cells (SCs), on the signal transduction pathway and phosphorylation of Synapsin I in a Human neuroblastoma cell line (NB-1). METHODS: NB-1s, NB-1s co-cultured with SCs, and a negative control group (NB-1 cells without ACR) were exposed to gradient concentrations of ACR for 48 h. Cell proliferation and viability were determined by MTT. Protein and mRNA expression levels of typical kinases (i.e., cAMP-dependent protein kinase [PKA], calcium/calmodulin-dependent protein kinase II [CaMKII], and mitogen-activated protein kinase-extracellular signal-regulated kinases [MAPK-Erk]), their phosphorylation status, as well as Synapsin I and its phosphorylation status, were tested by western blotting and polymerase chain reaction, respectively. Further, the effect of SCs on ACR-induced NB-1 cell toxicity was evaluated. RESULTS: (1) The MTT assay showed a sustained, dose- and time-dependent inhibition of NB-1s exposed to ACR. (2) ACR exposure increased the phosphorylation of CaMKII and PKA, which subsequently increased the phosphorylation of Synapsin I (at Serine603 [a substrate site of CaMKII] and Serine9 [a substrate site of PKA]). Pretreatment with CaMKII and PKA inhibitors blocked the ACR-mediated increase in phosphorylation. The above-described results were all significantly different when compared to the control group (p < 0.05). (3) When co-cultured with SCs, ACR-induced NB-1 inhibition was obviously decreased, and the trend of change of phosphorylated CaMKII, PKA, and Synapsin I were changed (first slightly increased and then decreased), which was inconsistent with what we observed in NB-1s cultured alone. CONCLUSIONS: The toxic effects of ACR on neurons may be mediated by CaMKII and PKA-dependent signaling pathways in which Synapsin I may act as a downstream effector. Furthermore, glial cells (SCs) may be able to prevent a certain degree of ACR-induced neuronal damage.

Assessment of DNA/Chromosome Damage in the Peripheral Blood Lymphocytes of Workers Exposed to Indium Compounds.

This study was conducted to investigate possible genotoxic effects resulting from occupational exposure to indium compounds. We performed a cytogenetic analysis of peripheral blood lymphocytes gathered from 57 individuals exposed to indium at an indium ingot production plant in Guangxi, China, and compared the results with those obtained from 63 control subjects. The lymphocytes from both groups were examined in the chromosomal aberrations (CAs) assay, cytokinesis-block micronucleus (CBMN) assay, and single-cell gel electrophoresis (comet) assay. Samples of personal breathing zone air were collected throughout the work shift of each subject. Blood and urine samples were collected before and after each work shift on the same day as the air samples were collected. Our assay results showed that workers in the indium production plant were exposed to significantly higher levels of indium (median exposure, 8.00 µg/m3) than the control subjects. Also, higher concentrations of urinary indium (U-In) were found in the exposed workers than the control subjects. When compared with the control subjects, the exposed workers showed higher levels of DNA damage as detected by the comet assay (tail length and TDNA%), significantly higher frequencies of CAs/100 cells, and increased CBMN frequencies. Moreover, the mean CBMN frequency in the non-smokers exposed to indium was significantly higher than that in the non-smoker control subjects (3.14‰ vs 1.00‰, respectively; P < .01). U-In levels, comet assay, CBMN, and CA test proved to be the most sensitive biological markers for detecting occupational exposure to indium compounds and can also be used to assess the health risks of the exposed workers.