North Sichuan Medical University

Enormous efforts have been made toward the translation of nanotechnology into medical practice, including cancer management. Generally the applications have fallen into two categories: diagnosis and therapy. Because the targets are often the same, the development of separate approaches can miss opportunities to improve efficiency and effectiveness. The unique physical properties of nanomaterials enable them to serve as the basis for superior imaging probes to locate and report cancerous lesions and as vehicles to deliver therapeutics preferentially to those lesions. These technologies for probes and vehicles have converged in the current efforts to develop nanotheranostics, nanoplatforms with both imaging and therapeutic functionalities. These new multimodal platforms are highly versatile and valuable components of the emerging trend toward personalized medicine, which emphasizes tailoring treatments to the biology of individual patients to optimize outcomes. The close coupling of imaging and treatment within a theranostic agent and the data about the evolving course of an illness that these agents provide can facilitate informed decisions about modifications to treatment. Magnetic nanoparticles, especially superparamagnetic iron oxide nanoparticles (IONPs), have long been studied as contrast agents for magnetic resonance imaging (MRI). Owing to recent progress in synthesis and surface modification, many new avenues have opened for this class of biomaterials. Such nanoparticles are not merely tiny magnetic crystals, but potential platforms with large surface-to-volume ratios. By taking advantage of the well-developed surface chemistry of these materials, researchers can load a wide range of functionalities, such as targeting, imaging and therapeutic features, onto their surfaces. This versatility makes magnetic nanoparticles excellent scaffolds for the construction of theranostic agents, and many efforts have been launched toward this goal. In this Account, we introduce the surface engineering techniques that we and others have developed, with an emphasis on how these techniques affect the role of nanoparticles as imaging or therapeutic agents. We and others have developed a set of chemical methods to prepare magnetic nanoparticles that possess accurate sizes, shapes, compositions, magnetizations, relaxivities, and surface charges. These features, in turn, can be harnessed to adjust the toxicity and stability of the nanoparticles and, further, to load functionalities, via various mechanisms, onto the nanoparticle surfaces.

Owing to their unique physical and chemical properties, magnetic iron oxide nanoparticles have become a powerful platform in many diverse aspects of biomedicine, including magnetic resonance imaging, drug and gene delivery, biological sensing, and hyperthermia. However, the biomedical applications of magnetic iron oxide nanoparticles arouse serious concerns about their pharmacokinetics, metabolism, and toxicity. In this review, the updated research on the biomedical applications and potential toxicity of magnetic iron oxide nanoparticles is summarized. Much more effort is required to develop magnetic iron oxide nanoparticles with improved biocompatible surface engineering to achieve minimal toxicity, for various applications in biomedicine.

Extracellular vesicles (EVs) are a collective term for nanoscale or microscale vesicles secreted by cells that play important biological roles. Mesenchymal stem cells are a class of cells with the potential for self-healing and multidirectional differentiation. In recent years, numerous studies have shown that EVs, especially those secreted by mesenchymal stem cells, can promote the repair and regeneration of various tissues and, thus, have significant potential in regenerative medicine. However, due to the rapid clearance capacity of the circulatory system, EVs are barely able to act persistently at specific sites for repair of target tissues. Hydrogels have good biocompatibility and loose and porous structural properties that allow them to serve as EV carriers, thereby prolonging the retention in certain specific areas and slowing the release of EVs. When EVs are needed to function at specific sites, the EV-loaded hydrogels can stand as an excellent approach. In this review, we first introduce the sources, roles, and extraction and characterization methods of EVs and describe their current application status. We then review the different types of hydrogels and discuss factors influencing their abilities to carry and release EVs. We summarize several strategies for loading EVs into hydrogels and characterizing EV-loaded hydrogels. Furthermore, we discuss application strategies for EV-loaded hydrogels and review their specific applications in tissue regeneration and repair. This article concludes with a summary of the current state of research on EV-loaded hydrogels and an outlook on future research directions, which we hope will provide promising ideas for researchers.

High sensitivity nanosensors utilize optical, mechanical, electrical, and magnetic relaxation properties to push detection limits of biomarkers below previously possible concentrations. The unique properties of nanomaterials and nanotechnology are exploited to design biomarker diagnostics. High-sensitivity recognition is achieved by signal and target amplification along with thorough pre-processing of samples. In this tutorial review, we introduce the type of detection signals read by nanosensors to detect extremely small concentrations of biomarkers and provide distinctive examples of high-sensitivity sensors. The use of such high-sensitivity nanosensors can offer earlier detection of disease than currently available to patients and create significant improvements in clinical outcomes.

OBJECTIVE: To summarize currently available evidence on maternal, fetal, and neonatal outcomes of pregnant women infected with Coronavirus Disease 2019 (COVID-19). MATERIAL AND METHODS: PubMed, Google Scholar, CNKI, Wanfang Data, VIP, and CBMdisc were searched for studies reporting maternal, fetal, and neonatal outcomes of women infected with COVID-19 published from 1 January 2020 to 26 March 2020. The protocol was registered with the Open Science Framework (DOI: 10.17605/OSF.IO/34ZAV). RESULTS: In total, 18 studies comprising 114 pregnant women were included in the review. Fever (87.5%) and cough (53.8%) were the most commonly reported symptoms, followed by fatigue (22.5%), diarrhea (8.8%), dyspnea (11.3%), sore throat (7.5%), and myalgia (16.3%). The majority of patients (91%) had cesarean delivery due to various indications. In terms of fetal and neonatal outcomes, stillbirth (1.2%), neonatal death (1.2%), preterm birth (21.3%), low birth weight (<2500 g, 5.3%), fetal distress (10.7%), and neonatal asphyxia (1.2%) were reported. There are reports of neonatal infection, but no direct evidence of intrauterine vertical transmission has been found. CONCLUSIONS: The clinical characteristics of pregnant women with COVID-19 are similar to those of non-pregnant adults. Fetal and neonatal outcomes appear good in most cases, but available data only include pregnant women infected in their third trimesters. Further studies are needed to ascertain long-term outcomes and potential intrauterine vertical transmission.

The transcription factor EB (TFEB) is an essential component of lysosomal biogenesis and autophagy for the adaptive response to food deprivation. To address the physiological function of TFEB in skeletal muscle, we have used muscle-specific gain- and loss-of-function approaches. Here, we show that TFEB controls metabolic flexibility in muscle during exercise and that this action is independent of peroxisome proliferator-activated receptor-γ coactivator1α (PGC1α). Indeed, TFEB translocates into the myonuclei during physical activity and regulates glucose uptake and glycogen content by controlling expression of glucose transporters, glycolytic enzymes, and pathways related to glucose homeostasis. In addition, TFEB induces the expression of genes involved in mitochondrial biogenesis, fatty acid oxidation, and oxidative phosphorylation. This coordinated action optimizes mitochondrial substrate utilization, thus enhancing ATP production and exercise capacity. These findings identify TFEB as a critical mediator of the beneficial effects of exercise on metabolism.

BACKGROUND: Microglial polarization with M1/M2 phenotype shifts and the subsequent neuroinflammatory responses are vital contributing factors for spinal cord injury (SCI)-induced secondary injury. Nuclear factor-κB (NF-κB) is considered the central transcription factor of inflammatory mediators, which plays a crucial role in microglial activation. Lysine acetylation of STAT1 seems necessary for NF-kB pathway activity, as it is regulated by histone deacetylases (HDACs). There have been no studies that have explained if HDAC inhibition by valproic acid (VPA) affects the NF-κB pathway via acetylation of STAT1 dependent of HDAC activity in the microglia-mediated central inflammation following SCI. We investigated the potential molecular mechanisms that focus on the phenotypic transition of microglia and the STAT1-mediated NF-κB acetylation after a VPA treatment. METHODS: The Basso-Beattie-Bresnahan locomotion scale, the inclined plane test, the blood-spinal cord barrier, and Nissl staining were employed to determine the neuroprotective effects of VPA treatment after SCI. Assessment of microglia polarization and pro-inflammatory markers, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and interferon (INF)-γ was used to evaluate the neuroinflammatory responses and the anti-inflammatory effects of VPA treatment. Immunofluorescent staining and Western blot analysis were used to detect HDAC3 nuclear translocation, activity, and NF-κB signaling pathway activation to evaluate the effects of VPA treatment. The impact of STAT1 acetylation on NF-kB pathway and the interaction between STAT1 and NF-kB were assessed to evaluate anti-inflammation effects of VPA treatment and also whether these effects were dependent on a STAT1/NF-κB pathway to gain further insight into the mechanisms underlying the development of the neuroinflammatory response after SCI. RESULTS: The results showed that the VPA treatment promoted the phenotypic shift of microglia from M1 to M2 phenotype and inhibited microglial activation, thus reducing the SCI-induced inflammatory factors. The VPA treatment upregulation of the acetylation of STAT1/NF-κB pathway was likely caused by the HDAC3 translocation to the nucleus and activity. These results indicated that the treatment with the VPA suppressed the expression and the activity of HDAC3 and enhanced STAT1, as well as NF-κB p65 acetylation following a SCI. The acetylation status of NF-kB p65 and the complex with NF-κB p65 and STAT1 inhibited the NF-kB p65 transcriptional activity and attenuated the microglia-mediated central inflammatory response following SCI. CONCLUSIONS: These results suggested that the VPA treatment attenuated the inflammatory response by modulating microglia polarization through STAT1-mediated acetylation of the NF-κB pathway, dependent of HDAC3 activity. These effects led to neuroprotective effects following SCI.

PURPOSE: Circular RNAs (circRNA) represent a novel class of widespread and diverse endogenous RNAs that regulate gene expression in mammals. microRNA-7 (miR-7) is a well-demonstrated suppressor of hepatocellular carcinoma (HCC). Recent studies have showed that one such circRNA, ciRS-7 (also termed as Cdr1as) was the inhibitor and sponge of miR-7 in the embryonic zebrafish midbrain and islet cells. However, the relationships among ciRS-7, miR-7 and clinical features of HCC remain to be clarified. METHODS: Expression levels of ciRS-7, miR-7 and three miR-7-targeted mRNAs in 108 pairs of HCC and their matched non-tumor tissues were examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The protein production of these three miR-7-targeted mRNAs was further verified by Western blot. The relationship between ciRS-7 level and clinicopathological features as well as the recurrence of HCC patients was analyzed. The univariate and multivariate logistic regression analyses were used to detect the risk factors of hepatic microvascular invasion (MVI). The correlation among ciRS-7, miR-7 and miR-7-targeted mRNAs was evaluated using Spearman's correlation test. RESULTS: There was no significant difference of ciRS-7 expression levels between the HCC tissues and the matched non-tumor tissues (0.67 ± 1.49 vs. 0.44 ± 0.45, p = 0.13), and the ciRS-7 levels in more than half of HCC tissues (65 out of 108, 60.2 %) were down-regulated when compared with their matched non-tumor tissues. However, the expression of ciRS-7 was significantly correlated with the following three clinicopathological characteristics of HCC patients: age <40 years (p = 0.02), serum AFP ≥400 ng/µl (p < 0.01) and hepatic MVI (p = 0.03). Meanwhile, up-regulated ciRS-7 expression was not only an independent risk factor of hepatic MVI but also had a capable predictive ability for MVI (AUC = 0.68, p = 0.001) at the cut-off value of 0.135. Furthermore, the expression of ciRS-7 in HCC tissues with concurrent MVI was inversely correlated with that of miR-7 (r = -0.39, p = 0.007) and positively related with that of two miR-7-targeted genes [PIK3CD (r = 0.55, p < 0.001) and p70S6K (r = 0.34, p = 0.021)]. In addition, the median recurrent time of patients from higher ciRS-7 level group was shorter than that of lower ciRS-7 group (18 vs. 25 months), but no significant difference was observed (p = 0.38). CONCLUSIONS: The expression levels of ciRS-7 were comparable between HCC and matched non-tumor tissues. However, the highly ciRS-7 expression in HCC tissues was significantly correlated with hepatic MVI, AFP level and younger age and thus partly related with the deterioration of HCC. Especially, ciRS-7 was one of the independent factors of hepatic MVI. These data suggested that ciRS-7 may be a promising biomarker of hepatic MVI and a novel therapy target for restraining MVI.

The dual-emissive N, S co-doped carbon dots (N, S-CDs) with a long emission wavelength were synthesized via solvothermal method. The N, S-CDs possess relatively high photoluminescence (PL) quantum yield (QY) (35.7%) towards near-infrared fluorescent peak up to 648 nm. With the advanced characterization techniques including X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), etc. It is found that the doped N, S elements play an important role in the formation of high QY CDs. The N, S-CDs exist distinct pH-sensitive feature with reversible fluorescence in a good linear relationship with pH values in the range of 1.0–13.0. What is more, N, S-CDs can be used as an ultrasensitive Ag+ probe sensor with the resolution up to 0.4 μM. This finding will expand the application of as prepared N, S-CDs in sensing and environmental fields.

During the past decade, immunotherapy targeting immune checkpoints has become an important component of the treatment paradigm for numerous malignancies, especially PD-1/PD-L1 blockade which was demonstrated to rejuvenate disabled T cells in cancer patients to achieve long-term remissions. However, the clinical outcome of PD-1/PD-L1 targeted monotherapy against solid malignancies is not satisfactory which may be related with the intricate tumor microenvironment. As a vital suppressive immunocyte in tumor microenvironment, Tregs are characterized by PD-1 and PD-L1 and demonstrated to contribute to the tumor progression. The latest studies have suggested that Tregs might be involved in the treatment of PD-1/PD-L1 blockade and PD-1/PD-L1 axis could influence Treg differentiation and function. However, the complicated relationship between PD-1/PD-L1 pathway and Tregs has not been fully clarified. Here, we explored the role of PD-1/PD-L1 axis in Treg development and function, as well as the potential mechanisms of PD-1/PD-L1 blockade resistance related with Tregs. Meanwhile, we discussed the combination therapy aimed at targeting PD-1/PD-L1 axis and Tregs, hoping to provide novel insights for the future cancer treatment.

BACKGROUND AND AIM: Dyslipidaemia is the main risk factor for coronary heart disease (CHD). Plasma lipid levels are conven-tionally used to predict coronary risk globally, but further studies are required to investigate whether the lipoprotein ratios are superior to conventional lipid parameters as predictors for CHD. METHODS: A hospital-based case-control study consisting of 738 CHD patients and 157 control subjects was conducted in a Chinese Han population. Demographic characteristics and plasma lipid or apolipoprotein data were collected. Univariate and multivariate logistic regression analyses were carried out to examine the relationship between the lipoprotein ratios and CHD risk. RESULTS: The CHD group had significantly higher age, non-high-density lipoprotein cholesterol (non-HDL-C), lipoprotein (a) [Lp(a)], triglyceride (TG)/HDL-C, total cholesterol (TC)/HDL-C, low-density lipoprotein cholesterol (LDL-C)/HDL-C, non-HDL-C/HDL-C, very low-density lipoprotein cholesterol (VLDL-C)/HDL-C, and apolipoprotein B100/apolipoprotein AI (apoB100/apoAI) than the control group (p < 0.05 for all). Moreover, the prevalence of male sex, smoking, and hypertension in the CHD group was significantly higher than in the control group. The results from univariate logistic regression analysis showed that the ratios of TC/HDL-C (OR 1.135, 95% CI 1.019-1.265), LDL-C/HDL-C (OR 1.216, 95% CI 1.033-1.431), non-HDL-C/HDL-C (OR 1.135, 95% CI 1.019-1.265), and apoB100/apoAI (OR 1.966, 95% CI 1.013-3.817) significantly increased the risk for CHD. By multivariate logistic regression analysis, the results were not materially altered and each of the four ratios was independently associated with CHD after adjustment for non-lipid coronary risk factors. ApoB100/apoAI showed the strongest association with CHD in both the univariate and multivariate logistic regression analyses. CONCLUSIONS: Our data indicate that the lipoprotein ratios are superior to conventional lipid parameters as predictors for CHD. Of the ratios, apoB100/apoAI is the best to predict CHD risk.

Abstract: Exosomes are small extracellular vesicles, ranging in size from 30– 150nm, which can be derived from various types of cells. In recent years, mammalian-derived exosomes have been extensively studied and found to play a crucial role in regulating intercellular communication, thereby influencing the development and progression of numerous diseases. Traditional Chinese medicine has employed plant-based remedies for thousands of years, and an increasing body of evidence suggests that plant-derived exosome-like nanovesicles (PELNs) share similarities with mammalian-derived exosomes in terms of their structure and function. In this review, we provide an overview of recent advances in the study of PELNs and their potential implications for human health. Specifically, we summarize the roles of PELNs in respiratory, digestive, circulatory, and other diseases. Furthermore, we have extensively investigated the potential shortcomings and challenges in current research regarding the mechanism of action, safety, administration routes, isolation and extraction methods, characterization and identification techniques, as well as drug-loading capabilities. Based on these considerations, we propose recommendations for future research directions. Overall, our review highlights the potential of PELNs as a promising area of research, with broad implications for the treatment of human diseases. We anticipate continued interest in this area and hope that our summary of recent findings will stimulate further exploration into the implications of PELNs for human health. Keywords: exosomes, nanocarriers, nanotherapeutics, plants, vesicles

Abstract Here, we show that NH 2 -MIL-88B(Fe) can be used as a peroxidase-like catalyst for Fenton-like degradation of methylene blue (MB) in water. The iron-based NH 2 -MIL-88B(Fe) metal organic framework (MOF) was synthesized by a facile and rapid microwave heating method. It was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, powder X-ray diffraction, and the Brunauer–Emmett–Teller method. The NH 2 -MIL-88B(Fe) MOF possesses intrinsic oxidase-like and peroxidase-like activities. The reaction parameters that affect MB degradation were investigated, including the solution pH, NH 2 -MIL-88B(Fe) MOF and H 2 O 2 concentrations, and temperature. The results show that the NH 2 -MIL-88B(Fe) MOF exhibits a wide working pH range (pH 3.0–11.0), temperature tolerance, and good recyclability for MB removal. Under the optimal conditions, complete removal of MB was achieved within 45 min. In addition, removal of MB was above 80% after five cycles, showing the good recyclability of NH 2 -MIL-88B(Fe). The NH 2 -MIL-88B(Fe) MOF has the features of easy preparation, high efficiency, and good recyclability for MB removal in a wide pH range. Electron spin resonance and fluorescence probe results suggest the involvement of hydroxyl radicals in MB degradation. These findings provide new insight into the application of high-efficient MOF-based Fenton-like catalysts for water purification.

INTRODUCTION: Traumatic brain injury (TBI) is associated with a profound immunological dysfunction manifested by a severe shift from T-helper type 1 (Th1) to T-helper type 2 (Th2) response. This predisposes patients to infections, sepsis, and adverse outcomes. Probiotic bacteria have been shown to balance the Th1/Th2 cytokines in allergic murine models and patients. For the present study, we hypothesized that the enteral administration of probiotics would adjust the Th1/Th2 imbalance and improve clinical outcomes in TBI patients. METHODS: We designed a prospective, randomized, single-blind study. Patients with severe TBI and Glasgow Coma Scale scores between 5 and 8 were included, resulting in 26 patients in the control group and 26 patients in the probiotic group. All patients received enteral nutrition via a nasogastric tube within 24 to 48 hours following admission. In addition, the probiotic group received 109 bacteria of viable probiotics per day for 21 days. The associated serum levels of Th1/Th2 cytokines, Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores, nosocomial infections, length of ICU stay, and 28-day mortality rate were studied. RESULTS: The patients responded to viable probiotics, and showed a significantly higher increase in serum IL-12p70 and IFNγ levels while also experiencing a dramatic decrease in IL-4 and IL-10 concentrations. APACHE II and SOFA scores were not significantly affected by probiotic treatment. Patients in the probiotic group experienced a decreased incidence of nosocomial infections towards the end of the study. Shorter ICU stays were also observed among patients treated with probiotic therapy. However, the 28-day mortality rate was unaffected. CONCLUSIONS: The present study showed that daily prophylactic administration of probiotics could attenuate the deviated Th1/Th2 response induced by severe TBI, and could result in a decreased nosocomial infection rate, especially in the late period. TRIAL REGISTRATION: ChiCTR-TRC-10000835.

Phytophthora infestans (P. infestans) is the causal agent of potato late blight, which caused the devastating Irish Potato Famine during 1845-1852. Until now, potato late blight is still the most serious threat to potato growth and has caused significant economic losses worldwide. Melatonin can induce plant innate immunity against pathogen infection, but the direct effects of melatonin on plant pathogens are poorly understood. In this study, we investigated the direct effects of melatonin on P. infestans. Exogenous melatonin significantly attenuated the potato late blight by inhibiting mycelial growth, changing cell ultrastructure, and reducing stress tolerance of P. infestans. Notably, synergistic anti-fungal effects of melatonin with fungicides on P. infestans suggest that melatonin could reduce the dose levels and enhance the efficacy of fungicide against potato late blight. A transcriptome analysis was carried out to mine downstream genes whose expression levels are affected by melatonin. The analysis of the transcriptome suggests that 66 differentially expressed genes involved in amino acid metabolic processes were significantly affected by melatonin. Moreover, the differentially expressed genes associated with stress tolerance, fungicide resistance, and virulence were also affected. These findings contribute to a new understanding of the direct functions of the melatonin on P. infestans and provide a potential ecofriendly biocontrol approach using a melatonin-based paradigm and application to prevent potato late blight.

We compared routine blood pictures in venous, fingertip and arterial blood and their measurement variation. A pair of venous and fingertip blood samples were simultaneously collected from 24 volunteers, and another pair of venous and arterial samples from another 12 volunteers. The volunteers were healthy adults, aged 20-22 years, with males and females in equal numbers. Three aliquots of blood were taken from each person for three measurements of blood counts, including haemoglobin concentration and haematocrit, using an automatic haematology analyser. Compared to arterial blood, there was a significant increase of erythrocyte count (2.7%) and haematocrit (3.1%) in the venous blood. The total and large leucocyte counts were significantly higher (9.2% and 12.6%, respectively) in the fingertip blood than in the venous blood. There were a decreasing number of leucocytes in the fingertip blood with repeated sampling. The intermeasurement variation for total leucocyte or haemoglobin measurement was significantly larger as measured with the fingertip blood or arterial blood than with the venous blood. The intermeasurement coefficients of variation of haemoglobin (1.3%) and small leucocyte ratio or platelet (approximately 4.0%) measurements with venous and arterial blood were the smallest and largest, respectively. Volume of arterial plasma was diminished by 2-3% after microcirculation. Elevation of total leucocyte count in the fingertip blood was mainly due to the increase of granulocytes. Measurement with venous blood was of better precision than with fingertip or arterial blood.

BACKGROUND: Gouty arthritis is characterized by the deposition of monosodium urate (MSU) within synovial joints and tissues due to increased urate concentrations. In this study, we explored the effect of the natural compound curcumin on the MSU crystal-stimulated inflammatory response. METHODS: THP-1-derived macrophages and murine RAW264.7 macrophages were pretreated with curcumin for 1 h and then stimulated with MSU suspensions for 24 h. The protein level of TLR4, MyD88, and IκBα, the activation of the NF-κB signaling pathway, the expression of the NF-κB downstream inflammatory cytokines, and the activity of NLRP3 inflammasome were measured by western blotting and ELISA. THP-1 and RAW264.7 cells were loaded with MitoTracker Green to measure mitochondrial content, and MitoTracker Red to detect mitochondrial membrane potential. To measure mitochondrial reactive oxygen species (ROS) levels, cells were loaded with MitoSOX Red, which is a mitochondrial superoxide indicator. The effects of curcumin on mouse models of acute gout induced by the injection of MSU crystals into the footpad and synovial space of the ankle, paw and ankle joint swelling, lymphocyte infiltration, and MPO activity were evaluated. RESULTS: Curcumin treatment markedly inhibited the degradation of IκBα, the activation of NF-κB signaling pathway, and the expression levels of the NF-κB downstream inflammatory genes such as IL-1β, IL-6, TNF-α, COX-2, and PGE2 in the MSU-stimulated THP-1-derived macrophages. Curcumin administration protected THP-1 and RAW264.7 cells from MSU induced mitochondrial damage through preventing mitochondrial membrane potential reduction, decreasing mitochondria ROS, and then inhibited the activity of NLRP3 inflammasome. Intraperitoneal administration of curcumin alleviated MSU crystal-induced paw and ankle joint swelling, inflammatory cell infiltration, and MPO activity in mouse models of acute gout. These results correlated with the inhibition of the degradation of IκBα, the phosphorylation levels of NF-κB subunits (p65 and p50), and the activity of NLRP3 inflammasome. CONCLUSION: Curcumin administration effectively alleviated MSU-induced inflammation by suppressing the degradation of IκBα, the activation NF-κB signaling pathway, the damage of mitochondria, and the activity of NLRP3 inflammasome. Our results provide a new strategy in which curcumin therapy may be helpful in the prevention of acute episodes of gout.

Despite the great potential of numerous antioxidants for pharmacotherapy of diseases associated with inflammation and oxidative stress, many challenges remain for their clinical translation. Herein, a superoxidase dismutase/catalase-mimetic material based on Tempol and phenylboronic acid pinacol ester simultaneously conjugated β-cyclodextrin (abbreviated as TPCD), which is capable of eliminating a broad spectrum of reactive oxygen species (ROS), is reported. TPCD can be easily synthesized by sequentially conjugating two functional moieties onto a β-cyclodextrin scaffold. The thus developed pharmacologically active material may be easily produced into antioxidant and anti-inflammatory nanoparticles, with tunable size. TPCD nanoparticles (TPCD NP) effectively protect macrophages from oxidative stress-induced apoptosis in vitro. Consistently, TPCD NP shows superior efficacies in three murine models of inflammatory diseases, with respect to attenuating inflammatory responses and mitigating oxidative stress. TPCD NP can also protect mice from drug-induced organ toxicity. Besides the passive targeting effect, the broad spectrum ROS-scavenging capability contributes to the therapeutic benefits of TPCD NP. Importantly, in vitro and in vivo preliminary experiments demonstrate the good safety profile of TPCD NP. Consequently, TPCD in its native and nanoparticle forms can be further developed as efficacious and safe therapies for treatment of inflammation and oxidative stress-associated diseases.

OBJECTIVES: The outbreak of novel coronavirus (COVID-19) provided an opportunity to undertake an online survey to study the relationships between body weight changes with changes in physical activity and lifestyle during an unusual event of forced isolation, or quarantine. METHODS: We distributed an electronic questionnaire using the popular social application WeChat to adults from any province of China except Hubei Province, the epicenter of the outbreak. The questionnaire asked for demographic information, body weight, physical activity, and lifestyle factors before and during the quarantine. RESULTS: Of 376 questionnaires returned, 339 were valid (90.2%). During the period of semi-lockdown, both females and males with BMI <24 gained weight, males with BMI ≥24 lost weight, and females with BMI ≥24 gained weight. The average steps per day and the average moderate or vigorous-intensity exercise declined significantly for both males and females during the semi-lockdown. Changes in body weight inversely correlated with changes in steps per day and moderate or vigorous-intensity exercise during the quarantine. CONCLUSIONS: Normal weight individuals, who are not normally troubled by overweight or obesity, had less awareness of weight gain than people with a BMI ≥ 24. Under the conditions of the semi-lockdown, they tended to gain weight.

OBJECTIVE: The aim of this study was to evaluate the short- and long-term effects as well as other parameters of repetitive transcranial magnetic stimulation (rTMS) on upper limb motor functional recovery after stroke. DATA SOURCES: The databases of PubMed, Medline, Science Direct, Cochrane, and Embase were searched for randomized controlled studies reporting effects of rTMS on upper limb motor recovery published before October 30, 2016. REVIEW METHODS: The short- and long-term mean effect sizes as well as the effect size of rTMS frequency of pulse, post-stroke onset, and theta burst stimulation patterns were summarized by calculating the standardized mean difference (SMD) and the 95% confidence interval using fixed/random effect models as appropriate. RESULTS: Thirty-four studies with 904 participants were included in this systematic review. Pooled estimates show that rTMS significantly improved short-term (SMD, 0.43; P < 0.001) and long-term (SMD, 0.49; P < 0.001) manual dexterity. More pronounced effects were found for rTMS administered in the acute phase of stroke (SMD, 0.69), subcortical stroke (SMD, 0.66), 5-session rTMS treatment (SMD, 0.67) and intermittent theta burst stimulation (SMD, 0.60). Only three studies reported mild adverse events such as headache and increased anxiety . CONCLUSIONS: Five-session rTMS treatment could best improve stroke-induced upper limb dyskinesia acutely and in a long-lasting manner. Intermittent theta burst stimulation is more beneficial than continuous theta burst stimulation. rTMS applied in the acute phase of stroke is more effective than rTMS applied in the chronic phase. Subcortical lesion benefit more from rTMS than other lesion site.