Exploring Gender Differences in the Association Between TyG Index and COPD: A Cross-Sectional Study from NHANES 1999-2018.

Purpose: This study examined gender differences in the association of Triglyceride-Glucose (TyG) index with the prevalence of chronic obstructive pulmonary disease (COPD), particularly in a non-diabetic population. Methods: The study leveraged data from the National Health and Nutrition Examination Survey (NHANES), spanning from 1999 to 2018, with a cohort of 23,456 participants. Logistic regression and restricted cubic spline analyses were employed to explore the relationship between the TyG index and COPD prevalence. Results: Statistical analyses revealed a significant positive association between the TyG index and COPD prevalence among non-diabetic women after adjustment for all covariates (OR=1.50; 95% CI, 1.08-2.08), supported by a linear relationship (P for non-linearity=0.298). No equivalent significant association was found in non-diabetic men (OR=1.00; 95% CI, 0.67-1.48). Within the diabetic group, the TyG index did not show a significant association with COPD prevalence, regardless of gender. Conclusion: Our study reveals a significant positive correlation between the TyG index and COPD prevalence in the non-diabetic population, marked by notable gender differences.

Exposure to coal dust exacerbates cognitive impairment by activating the IL6/ERK1/2/SP1 signaling pathway.

Coal dust (CD) is a common pollutant, and epidemiological surveys indicate that long-term exposure to coal dust not only leads to the occurrence of pulmonary diseases but also has certain impacts on cognitive abilities. However, there is little open-published literature on the effects and specific mechanisms of coal dust exposure on the cognition of patients with Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD). An animal model has been built in this study with clinical population samples to explore the changes in neuroinflammation and cognitive abilities with coal dust exposure. In the animal model, compared to C57BL/6 mice, APP/PS1 mice exposed to coal dust exhibited more severe cognitive impairment, accompanied by significantly elevated levels of neuroinflammatory factors Apolipoprotein E4 (AOPE4) and Interleukin-6 (IL6) in the hippocampus, and more severe neuronal damage. In clinical sample sequencing, it was found that there is significant upregulation of AOPE4, neutrophils, and IL6 expression in the peripheral blood of MCI patients compared to normal individuals. Mechanistically, cell experiments revealed that IL6 could promote the phosphorylation of ERK1/2 and enhance the expression of transcription factor SP1, thereby promoting AOPE4 expression. The results of this study suggest that coal dust can promote the upregulation of IL6 and AOPE4 in patients, exacerbating cognitive impairment.

Aberrant concordance among dynamics of spontaneous brain activity in patients with migraine without aura: A multivariate pattern analysis study.

Background: Alterations in the static and dynamic characteristics of spontaneous brain activity have been extensively studied to investigate functional brain changes in migraine without aura (MwoA). However, alterations in concordance among the dynamics of spontaneous brain activity in MwoA remain largely unknown. This study aimed to determine the possibilities of diagnosis based on the concordance indices. Methods: Resting-state functional MRI scans were performed on 32 patients with MwoA and 33 matched healthy controls (HCs) in the first cohort, as well as 36 patients with MwoA and 32 HCs in the validation cohort. The dynamic indices including fractional amplitude of low-frequency fluctuation, regional homogeneity, voxel-mirrored homotopic connectivity, degree centrality and global signal connectivity were analyzed. We calculated the concordance of grey matter volume-wise (across voxels) and voxel-wise (across time windows) to quantify the degree of integration among different functional levels represented by these dynamic indices. Subsequently, the voxel-wise concordance alterations were analyzed as features for multi-voxel pattern analysis (MVPA) utilizing the support vector machine. Results: Compared with that of HCs, patients with MwoA had lower whole-grey matter volume-wise concordance, and the mean value of volume-wise concordance was negatively correlated with the frequency of migraine attacks. The MVPA results revealed that the most discriminative brain regions were the right thalamus, right cerebellar Crus II, left insula, left precentral gyrus, right cuneus, and left inferior occipital gyrus. Conclusions: Concordance alterations in the dynamics of spontaneous brain activity in brain regions could be an important feature in the identification of patients with MwoA.

Altered effective connectivity from cerebellum to motor cortex in chronic low back pain: A multivariate pattern analysis and spectral dynamic causal modeling study.

To explore the central processing mechanism of pain perception in chronic low back pain (cLBP) using multi-voxel pattern analysis (MVPA) based on the static and dynamic fractional amplitude of low-frequency fluctuations (fALFF) analysis, and spectral dynamic causal modeling (spDCM). Thirty-two patients with cLBP and 29 matched healthy controls (HCs) for the first cohort and 24 patients with cLBP and 22 HCs for the validation cohort underwent resting-state fMRI scan. The alterations in static and dynamic fALFF were as classification features to distinguish patients with cLBP from HCs. The brain regions gotten from the MVPA results were used for further spDCM analysis. We found that the most discriminative brain regions that contributed to the classification were the right supplementary motor area (SMA.R), left paracentral lobule (PCL.L), and bilateral cerebellar Crus II. The spDCM results displayed decreased excitatory influence from the bilateral cerebellar Crus II to PCL.L in patients with cLBP compared with HCs. Moreover, the conversion of effective connectivity from the bilateral cerebellar Crus II to SMA.R from excitatory influence to inhibitive influence, and the effective connectivity strength exhibited partially mediated effects on Chinese Short Form Oswestry Disability Index Questionnaire (C-SFODI) scores. Our findings suggest that the cerebellum and its weakened or inhibited connections to the motor cortex may be one of the underlying feedback pathways for pain perception in cLBP, and partially mediate the degree of dysfunction.

Effect and mechanism of chlorogenic acid on cognitive dysfunction in mice by lipopolysaccharide-induced neuroinflammation.

Background: Neuroinflammation is an important factor causing numerous neurodegenerative pathologies. Inflammation can lead to abnormal neuronal structure and function and even death, followed by cognitive dysfunction. There is growing evidence that chlorogenic acid has anti-inflammatory effects and immunomodulatory activity. Purpose: The aim of this study was to elucidate the potential targets and molecular mechanisms of chlorogenic acid in the treatment of neuroinflammation. Methods: We used the lipopolysaccharide-induced neuroinflammation mouse model and the lipopolysaccharide-stimulated BV-2 cells in vitro model. Behavioral scores and experiments were used to assess cognitive dysfunction in mice. HE staining and immunohistochemistry were used to assess neuronal damage in the mouse brain. Immunofluorescence detected microglia polarization in mouse brain. Western blot and flow cytometry detected the polarization of BV-2 cells. The migration of BV-2 cells was detected by wound healing assay and transwell assay. Potential targets for chlorogenic acid to exert protective effects were predicted by network pharmacology. These targets were then validated using molecular docking and experiments. Results: The results of in vivo experiments showed that chlorogenic acid had an obvious ameliorating effect on neuroinflammation-induced cognitive dysfunction. We found that chlorogenic acid was able to inhibit BV-2 cells M1 polarization and promote BV-2 cells M2 polarization in vitro while also inhibiting the abnormal migration of BV-2 cells. Based on the network pharmacology results, we identified the TNF signaling pathway as a key signaling pathway in which chlorogenic acid exerts anti-neuroinflammatory effects. Among them, Akt1, TNF, MMP9, PTGS2, MAPK1, MAPK14, and RELA are the core targets for chlorogenic acid to function. Conclusion: Chlorogenic acid can inhibit microglial polarization toward the M1 phenotype and improve neuroinflammation-induced cognitive dysfunction in mice by modulating these key targets in the TNF signaling pathway.

Effect and mechanism of safranal on ISO-induced myocardial injury based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Sympathetic hyperactivation is a significant risk factor in the development of cardiovascular disease. Safranal has shown good myocardial protection in recent studies, but the mechanism of its role in myocardial injury caused by sympathetic hyperactivation remains unclear. AIM OF THE STUDY: The purpose of this study was to investigate whether safranal can effectively reduce isoproterenol (ISO)-induced myocardial injury in rats and H9c2 cells and to reveal its pharmacological action and target in inhibiting myocardial injury caused by sympathetic hyperactivation. MATERIALS AND METHODS: This study was carried out using network pharmacology, molecular docking, and in vitro and in vivo experiments. An in vivo model of myocardial injury was established by subcutaneous injection of ISO, and an in vitro model of H9c2 cell injury was induced by ISO. RESULTS: Safranal ameliorated myocardial injury caused by sympathetic hyperactivation by reducing the level of myocardial apoptosis. According to the results of network pharmacological analysis and molecular docking, the mechanism by which safranal alleviates myocardial injury may be closely related to the TNF signaling pathway, and safranal plays a role by regulating the core targets of the TNF signaling pathway. Safranal significantly inhibited the protein expression of TNF, PTGS2, MMP9 and pRELA. CONCLUSION: Safranal plays a protective role in myocardial injury induced by sympathetic hyperactivation by downregulating the TNF signaling pathway.

A true response of the brain network during electroacupuncture stimulation at scalp acupoints: An fMRI with simultaneous EAS study.

OBJECTIVES: The aim of this study was to explore simultaneous brain network responses to electroacupuncture stimulation (EAS) at scalp acupoints by accounting for placebo effects. MATERIALS AND METHODS: Sixty healthy subjects were recruited and randomly divided into two groups: Group 1 and Group 2. Functional magnetic resonance imaging (fMRI) was performed in Group 1 with sham acupuncture stimulation at acupoints Shenting (GV24) and Touwei (ST8) without EAS. Group 2 underwent verum EAS at the same acupoints during fMRI. Independent component analysis was used to analyze the fMRI data. Full-factor statistical analysis was used to compare the differences in fMRI data between the two groups and evaluate the changes in functional connectivity in brain networks after verum electrical stimulation (Group 1 [after sham electrical current stimulation - before sham electrical current stimulation] - Group 2 [after verum electrical current stimulation - before verum electrical current stimulation]) (p <.001, extent threshold k = 20 voxels). RESULTS: Six brain networks were identified. Significant increased functional connectivity was observed in the right and left executive control networks, sensorimotor network, and attention network, while decreased functional connectivity was mainly found in the default mode network. There were no statistically significant differences in the salience network. CONCLUSIONS: fMRI with simultaneous EAS provides a method to explore brain network responses due to EAS at scalp acupoints. The networks responsible for cognition are differentially activated by EAS in a coordinated manner.

The cumulative therapeutic effect of acupuncture in patients with migraine without aura: Evidence from dynamic alterations of intrinsic brain activity and effective connectivity.

We explored the dynamic alterations of intrinsic brain activity and effective connectivity after acupuncture treatment to investigate the underlying neurological mechanism of acupuncture treatment in patients with migraine without aura (MwoA). The Functional Magnetic Resonance Imaging (fMRI) scans were separately obtained at baseline, after the first and 12th acupuncture sessions in 40 patients with MwoA. Compared with the healthy controls (HCs), patients with MwoA mostly showed a decreased dynamic amplitude of low-frequency fluctuation (dALFF) variability in the rostral ventromedial medulla (RVM), superior lobe of left cerebellum (Cerebellum_Crus1_L), right precuneus (PCUN.R), and so on. The decreased dALFF variability of RVM, Cerebellum_Crus1_L, and PCUN.R progressively recovered after the first and 12th acupuncture treatment sessions as compared to the baseline. There was gradually increased dynamic effective connectivity (DEC) variability in RVM outflow to the right middle frontal gyrus, left insula, right precentral gyrus, and right supramarginal gyrus, and gradually enhanced DEC variability from the right fusiform gyrus inflow to RVM. Furthermore, the gradually increased DEC variability was found from Cerebellum_Crus1_L outflow to the left middle occipital gyrus and the left precentral gyrus, from PCUN.R outflow to the right thalamus. These dALFF variabilities were positively correlated with the frequency of migraine attacks and negatively correlated with disease duration at baseline. The dynamic Granger causality analysis (GCA) coefficients of this DEC variability were positively correlated with Migraine-Specific Quality of Life Questionnaire scores and negatively correlated with the frequency of migraine attacks and visual analog scale (VAS) scores after 12th acupuncture sessions. Our results were analyzed by a longitudinal fMRI in the absence of a sham acupuncture control group and provided insight into the dynamic alterations of brain activity and effective connectivity in patients with MwoA after acupuncture intervention. Acupuncture might relieve MwoA by increasing the effective connectivity of RVM, Cerebellum_Crus1_L, and PCUN.R to make up for the decreased dALFF variability in these brain areas.

Performance of a Flexible 12-Channel Head Coil in Comparison to Commercial 16- And 24-Channel Rigid Head Coils.

PURPOSE: To compare the performance of a 12-channel flexible head coil (HFC12) with commercial 16-channel (HRC16) and 24-channel (HRC24) rigid coils. METHODS: The phantom study was performed on a 1.5 T MR scanner with HFC12, HRC16, and HRC24. The SNR and noise correlation matrix of T1WI, T2WI, and diffusion weighted imaging (DWI) were measured. The SNR profiles were created according to the SNR. In addition, 1/g-factors were calculated in different acceleration directions. In the in vivo study, T1WI, T2WI, and DWI were performed in one healthy volunteer with three different coils. The SNR and noise correlation matrix were measured. RESULTS: In the phantom study and in vivo study, the SNR of HFC12 in the transverse, sagittal, and coronal planes was the highest, followed by HRC24, and that of HRC16 was the lowest. The SNR profiles showed that the SNR at the edge of HFC12 was the highest. The mean value of the noise correlation matrix of HFC12 was the highest. The 1/g-factor results showed that HFC12 obtained the best acceleration ability in the head-foot acceleration direction when the reduction factor was set to two. The SNR of HFC12 in most cortices was significantly higher than that of HRC16 and HRC24, except in the occipital cortex. The SNR of HRC24 in the occipital cortex was higher than that of HFC12. CONCLUSION: The SNR of HFC12 in T1WI, T2WI, and DWI was better than that of the HRC24 and HFC16. The SNR of HFC12 in the cortex was significantly higher than that of the commercial rigid head coil, except in the occipital cortex.

Electroacupuncture Synergistically Inhibits Proinflammatory Cytokine Production and Improves Cognitive Function in Rats with Cognitive Impairment due to Hepatic Encephalopathy through p38MAPK/STAT3 and TLR4/NF-κB Signaling Pathways.

OBJECTIVE: To investigate the effect of electroacupuncture (EA) on cognitive dysfunction in rats with hepatic encephalopathy and its underlying mechanism. METHODS: Fifty Wistar rats were randomly divided into a normal group (n = 10) and model group (n = 40). Rat models of hepatic encephalopathy were established by administration of carbon tetrachloride and thioacetamide for a total of 12 weeks. At the 9th week after modeling, rats with cognitive impairment in the model group were identified by conducting the Morris water maze test, which were then randomly divided into a control group (CCl4) and treatment groups including EA group (CCl4 + EA), lactulose group (CCl4 + Lac), and EA plus lactulose group (CCl4 + CM), with 9 rats in each group. At the end of the 9th week, rats in CCl4 + Lac and CCl4 + CM groups had lactulose gavage at a dose of 10 mL/kg body weight, while normal control and CCl4 groups had gavage with the same volume of normal saline once a day for 21 days until the end of the experiment. Rats in CCl4 + EA and CCl4 + CM groups underwent acupuncture at Baihui (GV[DU]20), Shenting (GV[DU]24), and Zusanli (ST36) acupoints, among which EA at Baihui and Shenting acupoints were given once daily for 30 min lasting for 21 consecutive days. The effect of the treatment was measured by the Morris water maze test for learning and memory ability and magnetic resonance spectroscopy (MRS) for neuronal metabolism in the hippocampus of rats with hepatic encephalopathy. Pathological change in the rat hippocampus was observed by HE staining, while serum ammonia and liver function markers were detected. Western blot and real-time fluorescent quantitative PCR were used to detect the expressions of specific genes and proteins in the brain tissue. RESULTS: Compared with those in the control group, rats undergoing EA had significantly shortened escape latency and increased number of platform crossing. H&E staining confirmed that EA improved brain tissue necrosis and ameliorated nuclear pyknosis in rats with hepatic encephalopathy. Significantly decreased levels of serum ammonia, alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBil), and total bile acid (TBA) were observed in rats undergoing EA, as well as improved levels of total protein (TP) and albumin (ALB). In addition, EA inhibited the brain expressions of TNF-α, IL-1ß, IL-6, iNOS, TLR4, MyD88, NF-κB, p38MAPK, phosphorylated (p)-p38MAPK, STAT3, and p-STAT3 genes, as well as protein expressions of TNF-α, IL-6, TLR4, MyD88, NF-κB, p38MAPK, p-p38MAPK, STAT3, and p-STAT3. MRS showed increased Glx/Cr and decreased NAA/Cr, Cho/Cr and mI/Cr in the control group, and EA significantly reversed such changes in Glx/Cr and mI/Cr values. CONCLUSION: EA ameliorated the production of excessive proinflammatory cytokines in the hippocampus of rats with cognitive dysfunction secondary to hepatic encephalopathy, which also gave rise to subsequent changes such as reduced blood ammonia level, brain-protective activated astrocytes, and lower degree of brain tissue injury. The p38MAPK/STAT3 and TLR4/MyD88/NF-κB signaling pathways may be involved. EA can also improve the metabolism of NAA and Cho in the rat hippocampus and thereby improve learning and memory abilities.

Spinal Manipulative Therapy Alters Brain Activity in Patients With Chronic Low Back Pain: A Longitudinal Brain fMRI Study.

Background: Spinal manipulative therapy (SMT) helps to reduce chronic low back pain (cLBP). However, the underlying mechanism of pain relief and the neurological response to SMT remains unclear. We utilized brain functional magnetic resonance imaging (fMRI) upon the application of a real-time spot pressure mechanical stimulus to assess the effects of SMT on patients with cLBP. Methods: Patients with cLBP (Group 1, n = 14) and age-matched healthy controls without cLBP (Group 2, n = 20) were prospectively enrolled. Brain fMRI was performed for Group 1 at three time points: before SMT (TP1), after the first SMT session (TP2), and after the sixth SMT session (TP3). The healthy controls (Group 2) did not receive SMT and underwent only one fMRI scan. During fMRI scanning, a real-time spot pressure mechanical stimulus was applied to the low back area of all participants. Participants in Group 1 completed clinical questionnaires assessing pain and quality of life using a visual analog scale (VAS) and the Chinese Short Form Oswestry Disability Index (C-SFODI), respectively. Results: Before SMT (TP1), there were no significant differences in brain activity between Group 1 and Group 2. After the first SMT session (TP2), Group 1 showed significantly greater brain activity in the right parahippocampal gyrus, right dorsolateral prefrontal cortex, and left precuneus compared to Group 2 (P < 0.05). After the sixth SMT session (TP3), Group 1 showed significantly greater brain activity in the posterior cingulate gyrus and right inferior frontal gyrus compared to Group 2 (P < 0.05). After both the first and sixth SMT sessions (TP2 and TP3), Group 1 had significantly lower VAS pain scores and C-SFODI scores than at TP1 (P < 0.001). Conclusion: We observed alterations in brain activity in regions of the default mode network in patients with cLBP after SMT. These findings suggest the potential utility of the default mode network as a neuroimaging biomarker for pain management in patients with cLBP. Clinical Trial Registration: Chinese Clinical Trial Registry, identifier ChiCTR1800015620.

Gold Nanorods Combined with an Near Infrared Laser for the Establishment of a Precise Posttraumatic Osteoarthritis Model.

Objective: To investigate the innovative application of gold nanorods combined with a laser in posttraumatic osteoarthritis (PTOA) modeling and to discuss the possible mechanisms. Methods: Electron microscopy was used to characterize the gold nanorods. Cell counting kit-8 assay and enzyme-linked immunosorbent assay were used to evaluate cell proliferation and cytotoxicity. An infrared spectroscopy (IR) thermal camera was used to monitor the temperature changes of gold nanorods with or without the laser treatment. Furthermore, western blotting was used to evaluate the expression of related proteins in response to the indicated treatments. Finally, microcomputed tomography (micro-CT) was used to determine the structural changes in knee joints. Changes in the cartilage and various other tissues were assessed by histological examination. Results: The characteristics and biosafety of the gold nanorods were confirmed. Our study showed that gold nanorods combined with the laser inhibited cell viability, but the gold nanorods or laser alone did not affect cell viability. Moreover, the effect on cell viability was time dependent. Similarly, only gold nanorods with the laser caused the apoptosis of cartilage cells and the upregulation of IL-1ß, MMP-13 and Comp. We injected gold nanorods and used laser irradiation to develop an osteoarthritis (OA) model. The temperature of the knees in the OA model increased to 60 °C and then remained at approximately 60 °C. As the time increased, gold nanorods combined with the laser caused more injuries and degeneration in the knee joints. Conclusion: OA models that were established using gold nanorods and a laser were precise, controllable, observable and stable and could be an excellent premise for investigating the exact mechanisms underlying OA and exploring new treatment strategies.

Porous Se@SiO2 nanocomposite promotes migration and osteogenic differentiation of rat bone marrow mesenchymal stem cell to accelerate bone fracture healing in a rat model.

Background: Delay or failure of bone union is a significant clinical challenge all over the world, and it has been reported that bone marrow mesenchymal stem cells (BMSCs) offer a promising approach to accelerate bone fracture healing. Se can modulate the proliferation and differentiation of BMSCs. Se-treatment enhances the osteoblastic differentiation of BMSCs and inhibiting the differentiation and formation of mature osteoclasts. The purpose of this study was to assess the effects of porous Se@SiO2 nanocomposite on bone regeneration and the underlying biological mechanisms. Methods: We oxidized Se2- to develop Se quantum dots, then we used the Se quantum dots to form a solid Se@SiO2 nanocomposite which was then coated with polyvinylpyrrolidone (PVP) and etched in hot water to synthesize porous Se@SiO2 nanocomposite. We used XRD pattern to assess the phase structure of the solid Se@SiO2 nanocomposite. The morphology of porous Se@SiO2 nanocomposite were evaluated by scanning electron microscope (SEM) and the biocompatibility of porous Se@SiO2 nanocomposite were investigated by cell counting kit-8 (CCK-8) assays. Then, a release assay was also performed. We used a Transwell assay to determine cell mobility in response to the porous Se@SiO2 nanocomposite. For in vitro experiments, BMSCs were divided into four groups to detect reactive oxygen species (ROS) generation, cell apoptosis, alkaline phosphatase activity, calcium deposition, gene activation and protein expression. For in vivo experiments, femur fracture model of rats was constructed to assess the osteogenic effects of porous Se@SiO2 nanocomposite. Results: In vitro, intervention with porous Se@SiO2 nanocomposite can promote migration and osteogenic differentiation of BMSCs, and protect BMSCs against H2O2-induced inhibition of osteogenic differentiation. In vivo, we demonstrated that the porous Se@SiO2 nanocomposite accelerated bone fracture healing using a rat femur fracture model. Conclusion: Porous Se@SiO2 nanocomposite promotes migration and osteogenesis differentiation of rat BMSCs and accelerates bone fracture healing, and porous Se@SiO2 nanocomposite may provide clinic benefit for bone tissue engineering.

Porous Se@SiO2 nanocomposites protect the femoral head from methylprednisolone-induced osteonecrosis.

BACKGROUND: Methylprednisolone (MPS) is an important drug used in therapy of many diseases. However, osteonecrosis of the femoral head is a serious damage in the MPS treatment. Thus, it is imperative to develop new drugs to prevent the serious side effect of MPS. METHODS: The potential interferences Se@SiO2 nanocomposites may have to the therapeutic effect of methylprednisolone (MPS) were evaluated by classical therapeutic effect index of acute respiratory distress syndrome (ARDS), such as wet-to-dry weight ratio, inflammatory factors IL-1ß and TNF-α. And oxidative stress species (ROS) index like superoxide dismutase (SOD) and glutathione (GSH) were tested. Then, the protection effects of Se@SiO2 have in osteonecrosis of the femoral head (ONFH) were evaluated by micro CT, histologic analysis and Western-blot analysis. RESULTS: In the present study, we found that in the rat model of ARDS, Se@SiO2 nanocomposites induced SOD and GSH indirectly to reduce ROS damage. The wet-to-dry weight ratio of lung was significantly decreased after MPS treatment compared with the control group, whereas the Se@SiO2 did not affect the reduced wet-to-dry weight ratio of MPS. Se@SiO2 also did not impair the effect of MPS on the reduction of inflammatory factors IL-1ß and TNF-α, and on the alleviation of structural destruction. Furthermore, micro CT and histologic analysis confirmed that Se@SiO2 significantly alleviate MPS-induced destruction of femoral head. Moreover, compared with MPS group, Se@SiO2 could increase collagen II and aggrecan, and reduce the IL-1ß level in the cartilage of femoral head. In addition, the biosafety of Se@SiO2 in vitro and in vivo were supported by cell proliferation assay and histologic analysis of main organs from rat models. CONCLUSION: Se@SiO2 nanocomposites have a protective effect in MPS-induced ONFH without influence on the therapeutic activity of MPS, suggesting the potential as effective drugs to avoid ONFH in MPS therapy.

Se@SiO2 nanocomposites attenuate doxorubicin-induced cardiotoxicity through combatting oxidative damage.

Doxorubicin (DOX) is an effective anticancer drug which is widely used in clinical treatment. However, the severe cardiotoxicity limits its use. Thus, it is an urgent need to attenuate the toxicity of DOX without impairing its efficacy. Many studies show that Se may protect normal tissues from damages of some anticancer drugs. Recently, Se@SiO2 nanocomposites emerges as better substitutes for direct element Se in treatment of cancer cells for their ideal biocompatibility. In the present article, we synthesized Se@SiO2 nanocomposites and confirmed their characterization according to previous studies. We accomplished a conjunctive use of Se@SiO2 nanocomposites with DOX then explored the toxicity and efficacy of this combination. In the in vivo experiments, the survival rate of mice with DOX treatment was significantly increased by Se@SiO2. And Se@SiO2 has few interference to the therapeutic effect of DOX. Particularly, Se@SiO2 significantly attenuated DOX-induced myocardial tissue damage (serum index, apoptosis index, western-blot index) and protected mice from reduction in LVEF induced by DOX in mice model. In summary, we concluded that the protective effect of Se@SiO2 in DOX-induced cardiotoxicity was possibly attributable to the inhibition of ROS production, showing great potential of Se@SiO2 nanocomposite in the clinical use of DOX.

Exchangeability of FITC-SiO2 Nanoparticles Between Cancer Cells Increases the Range of Drug Delivery.

Drug delivery system studies aim to improve nanoparticle (NP) formulation to enable efficient delivery of NPs to tumors. However, NPs must be transported by blood or through direct injection. How NPs leave the circulatory system and how NPs diffuse into a tumor remain unclear, and this uncertainty is a limitation of drug delivery systems. The intimate connection between these questions and metabolism may be related to their biosafety in vivo. Thus, in this study, classical carrier SiO2 NPs were used as typical transport NPs, and fluorescein isothiocyanate (FITC) was used as the representative drug and tracer. As exosome and tunneling nanotubes (TNTs) are the most relevant mechanism for NP transportation and considering the local situation in a tumor, we focused on identifying this phenomenon and investigating TNTs. In conclusion, we effectively demonstrated that NPs can be transferred from cell to cell. Nanotubes may play an important role in this process.

Inhibition of cancer cell migration with CuS@ mSiO2-PEG nanoparticles by repressing MMP-2/MMP-9 expression.

The metastasis of cancer cells is a vital aspect of disease progression and therapy. Although a few nanoparticles (NPs) aimed at controlling metastasis in cancer therapy have been reported, the NPs are normally combined with drugs, yet the direct therapeutic effects of the NPs are not reported. To study the direct influence of NPs on cancer metastasis, the potential suppression capacity of CuS@mSiO2-PEG NPs to tumor cell migration, a kind of typical photothermal NPs, was systemically evaluated in this study. Using CuS@mSiO2-PEG NP stimulation and a transwell migration assay, we found that the migration of HeLa cells was significantly decreased. This phenomenon may be associated with two classical proteins in metastasis: matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9). In addition, the mechanism may closely associate with non-receptor tyrosine kinase protein (SRC)/focal adhesion kinase (FAK) signaling pathway which varies in vivo and in vitro. To confirm the differences in the expression of SRC and FAK, related inhibitors were studied for additional comparison. Also, the results indicated that even though the migration inhibition was closely related to SRC and FAK signaling pathway, there may be another unknown regulation mechanism existing and its metastasis inhibition was significant. Confirmed by long-term survival curve study, CuS@mSiO2-PEG NPs significantly reduced the metastasis of cancer cells and improved the survival rates of metastasis in a mouse model. Thus, we believe that the direct influence of NPs on cancer cell metastasis is a promising study topic.

Treatment of steroid-induced osteonecrosis of the femoral head using porous Se@SiO2 nanocomposites to suppress reactive oxygen species.

Reducing oxidative stress (ROS) have been demonstrated effective for steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH). Selenium (Se) plays an important role in suppressing oxidative stress and has huge potential in ONFH treatments. However the Se has a narrow margin between beneficial and toxic effects which make it hard for therapy use in vivo. In order to make the deficiency up, a control release of Se (Se@SiO2) were realized by nanotechnology modification. Porous Se@SiO2 nanocomposites have favorable biocompatibility and can reduced the ROS damage effectively. In vitro, the cck-8 analysis, terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) stain and flow cytometry analysis showed rare negative influence by porous Se@SiO2 nanocomposites but significantly protective effect against H2O2 by reducing ROS level (detected by DCFH-DA). In vivo, the biosafety of porous Se@SiO2 nanocomposites were confirmed by the serum biochemistry, the ROS level in serum were significantly reduced and the curative effect were confirmed by Micro CT scan, serum Elisa assay (inflammatory factors), Western blotting (quantitative measurement of ONFH) and HE staining. It is expected that the porous Se@SiO2 nanocomposites may prevent steroid-induced ONFH by reducing oxidative stress.