Magnetic modulation of lysosomes for cancer therapy.

Lysosomes play a central role in biochemical signal transduction and oxidative stress in cells. Inducing lysosome membrane penetration (LMP) to cause lysosomal-dependent cell death (LCD) in tumor cells is an effective strategy for cancer therapy. Chemical drugs can destroy the stability of lysosomes by neutralizing protons within the lysosomes or enhancing the fragility of the lysosomal membranes. However, there remain several unsolved problems of traditional drugs in LMP induction due to insufficient lysosomal targeting, fast metabolism, and toxicity in normal cells. With the development of nanotechnology, magnetic nanoparticles have been demonstrated to target lysosomes naturally, providing a versatile tool for lysosomal modulation. Combined with excellent tissue penetration and spatiotemporal manipulability of magnetic fields, magnetic modulation of lysosomes progresses rapidly in inducing LMP and LCD for cancer therapy. This review comprehensively discussed the strategies of magnetic modulation of lysosomes for cancer therapy. The intrinsic mechanisms of LMP-induced LCD were first introduced. Then, the modulation of lysosomes by diverse physical outputs of magnetic fields was emphatically discussed. Looking forward, this review will shed the light on the prospect of magnetic modulation of lysosomes, inspiring future research of magnetic modulation strategy in cancer therapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Arresting the G2/M phase empowers synergy in magnetic nanomanipulator-based cancer mechanotherapy and chemotherapy.

Using mechanical cues for cancer cells can realize precise control and efficient therapeutic effects. However, the cell cycle-specific response for dynamic mechanical manipulation is barely investigated. Here, RGD-modified iron oxide nanomanipulators were utilized as the intracellular magneto-mechanical transducers to investigate the mechanical impacts on the cell cycle under a dynamic magnetic field for cancer treatment. The G2/M phase was identified to be sensitive to the intracellular magneto-mechanical modulation with a synergistic treatment effect between the pretreatment of cell cycle-specific drugs and the magneto-mechanical destruction, and thus could be an important mechanical-targeted phase for regulation of cancer cell death. Finally, combining the cell cycle-specific drugs with magneto-mechanical manipulation could significantly inhibit glioma and breast cancer growth in vivo. This intracellular mechanical stimulus showed cell cycle-dependent cytotoxicity and could be developed as a spatiotemporal therapeutic modality in combination with chemotherapy drugs for treating deep-seated tumors.

Sophisticated Magneto-Mechanical Actuation Promotes In Situ Stem Cell Assembly and Chondrogenesis for Treating Osteoarthritis.

Abnormal mechanical loading often leads to the progressive degradation of cartilage and causes osteoarthritis (OA). Although multiple mechanoresponsive strategies based on biomaterials have been designed to restore healthy cartilage microenvironments, methods to remotely control the on-demand mechanical forces for cartilage repair pose significant challenges. Here, a magneto-mechanically controlled mesenchymal stem cell (MSC) platform, based on the integration of intercellular mechanical communication and intracellular mechanosignaling processes, is developed for OA treatment. MSCs loaded with antioxidative melanin@Fe3O4 magnetic nanoparticles (Magcells) rapidly assemble into highly ordered cell clusters with enhanced cell-cell communication under a time-varying magnetic field, which enables long-term retention and differentiation of Magcells in the articular cavity. Subsequently, via mimicking the gait cycle, chondrogenesis can be further enhanced by the dynamic activation of mechanical signaling processes in Magcells. This sophisticated magneto-mechanical actuation strategy provides a paradigm for developing mechano-therapeutics to repair cartilage in OA treatment.

Photomagnetically Powered Spiky Nanomachines with Thermal Control of Viscosity for Enhanced Cancer Mechanotherapy.

Nanomachines with active propulsion have emerged as an intelligent platform for targeted cancer therapy. Achieving an efficient locomotion performance using an external energy conversion is a key requirement in the design of nanomachines. In this study, inspired by diverse spiky structures in nature, a photomagnetically powered nanomachine (PMN) with a spiky surface and thermally dependent viscosity tunability is proposed to facilitate mechanical motion in lysosomes for cancer mechanotherapy. The hybrid nanomachine is integrated with magnetic nanoparticles as the core and covered with gold nanotips. Physical simulations and experimental results prove that the spiky structure endows nanomachines with an obvious photomagnetic coupling effect in the NIR-II region through the alignment and orienting movement of plasmons on the gold tips. Using a coupling-enhanced magnetic field, PMNs are efficiently assembled into chain-like structures to further elevate energy conversion efficiency. Notably, PMNs with the thermal control of viscosity are efficiently propelled under simultaneously applied dual external energy sources in cell lysosomes. Enhanced mechanical destruction of cancer cells via PMNs is confirmed both in vitro and in vivo under photomagnetic treatment. This study provides a new direction for designing integrated nanomachines with active adaptability to physiological environments for cancer treatment.

Clinical effect of different maintenance doses of caffeine citrate in the treatment of preterm infants requiring assisted ventilation: a pilot multicenter study. / ä¸åŒç»´æŒå‰‚é‡æž¸æ©¼é ¸å’–å•¡å› å¯¹è¾ åŠ©é€šæ°”æ—©äº§å„¿çš„ç–—æ•ˆè¯„ä¼°ï¼šä¸€é¡¹åˆæ­¥å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS: This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.

An Engineered Bacteria-Hybrid Microrobot with the Magnetothermal Bioswitch for Remotely Collective Perception and Imaging-Guided Cancer Treatment.

Microrobots driven by multiple propelling forces hold great potential for noninvasively targeted delivery in the physiologic environment. However, the remotely collective perception and precise propelling in a low Reynold's number bioenvironment remain the major challenges of microrobots to achieve desired therapeutic effects in vivo. Here, we reported a biohybrid microrobot that integrated with magnetic, thermal, and hypoxia sensitivities and an internal fluorescent protein as the dual reporter of thermal and positioning signals for targeted cancer treatment. There were three key elements in the microrobotic system, including the magnetic nanoparticle (MNP)-loaded probiotic Escherichia coli Nissle1917 (EcN@MNP) for spatially magnetic and hypoxia perception, a thermal-logic circuit engineered into the bacteria to control the biosynthesis of mCherry as the temperature and positioning reporter, and NDH-2 enzyme encoded in the EcN for enhanced anticancer therapy. According to the fluorescent-protein-based imaging feedback, the microrobot showed good thermal sensitivity and active targeting ability to the tumor area in a collective manner under the magnetic field. The cancer cell apoptosis was efficiently triggered in vitro and in vivo by the hybrid microrobot coupled with the effects of magnetothermal ablation and NDH-2-induced reactive oxygen species (ROS) damage. Our study demonstrates that the biohybrid EcN microrobot is an ideal platform to integrate the physical, biological, and chemical properties for collective perception and propelling in targeted cancer treatment.

Adaptive Control of Nanomotor Swarms for Magnetic-Field-Programmed Cancer Cell Destruction.

Magnetic nanomotors (MNMs), powered by a magnetic field, are ideal platforms to achieve versatile biomedical applications in a collective and spatiotemporal fashion. Although the programmable swarm of MNMs that mimics the highly ordered behaviors of living creatures has been extensively studied at the microscale, it is of vital importance to manipulate MNM swarms at the nanoscale for on-demand tasks at the cellular level. In this work, a Cy5-tagged caspase-3-specific peptide-modified MNM is designed, and the adaptive control behaviors of MNM swarms are revealed in lysosomes to induce the cancer cell apoptosis under a rotating magnetic field (RMF). A magneto-programmed vortex is predicted to occur with swarms under RMF by the finite element method model and verified in vitro. According to the dynamic model and numerical simulation, the critical rotating frequency under which MNMs are out of step is strongly correlated to their assembling and swarming properties. The adaptivity of swarms maximizes the synchronous rotation to achieve an optimal energy conversion rate. The frequency-adapted controllability of MNM swarms for cancer cell apoptosis is observed in real time in vitro and in vivo. This work provides theoretical and experimental insights to adaptively control MNM swarms for cancer treatment.

Programmable ROS-Mediated Cancer Therapy via Magneto-Inductions.

Reactive oxygen species (ROS), a group of oxygen derived radicals and derivatives, can induce cancer cell death via elevated oxidative stress. A spatiotemporal approach with safe and deep-tissue penetration capabilities to elevate the intracellular ROS level is highly desirable for precise cancer treatment. Here, a mechanical-thermal induction therapy (MTIT) strategy is developed for a programmable increase of ROS levels in cancer cells via assembly of magnetic nanocubes integrated with alternating magnetic fields. The magneto-based mechanical and thermal stimuli can disrupt the lysosomes, which sequentially induce the dysfunction of mitochondria. Importantly, intracellular ROS concentrations are responsive to the magneto-triggers and play a key role for synergistic cancer treatment. In vivo experiments reveal the effectiveness of MTIT for efficient eradication of glioma and breast cancer. By remote control of the force and heat using magnetic nanocubes, MTIT is a promising physical approach to trigger the biochemical responses for precise cancer treatment.

Bioinspired Soft Microrobots with Precise Magneto-Collective Control for Microvascular Thrombolysis.

New-era soft microrobots for biomedical applications need to mimic the essential structures and collective functions of creatures from nature. Biocompatible interfaces, intelligent functionalities, and precise locomotion control in a collective manner are the key parameters to design soft microrobots for the complex bio-environment. In this work, a biomimetic magnetic microrobot (BMM) inspired by magnetotactic bacteria (MTB) with speedy motion response and accurate positioning is developed for targeted thrombolysis. Similar to the magnetosome structure in MTB, the BMM is composed of aligned iron oxide nanoparticle (MNP) chains embedded in a non-swelling microgel shell. Linear chains in BMMs are achieved due to the interparticle dipolar interactions of MNPs under a static magnetic field. Simulation results show that, the degree and speed of assembly is proportional to the field strength. The BMM achieves the maximum speed of 161.7 µm s-1 and accurate positioning control under a rotating magnetic field with less than 4% deviation. Importantly, the locomotion analyses of BMMs demonstrate the frequency-dependent synchronization under 8 Hz and asynchronization at higher frequencies due to the increased drag torque. The BMMs can deliver and release thrombolytic drugs via magneto-collective control, which is promising for ultra-minimal invasive thrombolysis.

Plasma exosomal prion protein levels are correlated with cognitive decline in PD patients.

OBJECTIVE: Cognitive decline is a common non-motor symptom of Parkinson disease (PD), and cellular prion protein (PrPC) has been suggested to play a role in this process. This study aimed to investigate the correlation between plasma exosomal prion protein and cognitive decline in PD patients. METHOD: A total of 60 participants, which included 23 PD patients without cognitive impairment (the PD-NCI group), 17 PD patients with cognitive impairment (the PD-CI group) and 20 health controls were included in this study. All participants received a complete evaluation of motor symptoms as well as non-motor symptoms, which include devaluations of cognitive function(assessed with the Montreal Cognitive Assessment (MoCA)) and their psychiatric state(assessed with the Hamilton Anxiety Scale(HAM-A) and Hamilton Depression Scale(HAMD-17)). We used an enzyme-linked immunosorbent assay (ELISA) to measure the plasma exosomal prion protein level. The exosomal marker Heat shock protein 70 (HSP 70) was used to normalize the protein level to the exosome content. RESULT: In PD patients, the plasma exosomal prion protein concentration was negatively correlated with the cognitive level. The plasma exosomal prion protein concentration was significantly higher in the PD-CI group than in the control group (p < 0.05) and the PD-NCI group (p < 0.05).Multivariate regression analysis indicated that plasma exosomal prion protein levels were significantly associated with the cognitive level (t=-3.185, P = 0.001) after adjusting for age, education, disease duration, H&Y stage and MDS-UPDRS-III scores. CONCLUSION: The plasma exosomal prion protein level is correlated with cognitive decline in PD patients and might be a potential biomarker for PD patients at risk for cognitive impairment.

Current views of complications associated with neonatal ventilation.

Infants born prematurely require external respiratory support device like ventilation for the purpose of life saving. However, these ventilation machines have complications that sometimes unfortunately result in morbidity. New ventilation techniques have been developed to prevent morbidity, but have yet to be fully evaluated. The present review article would discuss current aspects of this life saving gear especially for pediatric patients in clinical setting. Besides basic ventilation apparatus, advancements in the filed like proportional assist ventilation, volume targeted ventilation would be discussed.

Ion-Conductive and Thermal Properties of a Synergistic Poly(ethylene carbonate)/Poly(trimethylene carbonate) Blend Electrolyte.

Electrolytes comprising poly(ethylene carbonate) (PEC)/poly(trimethylene carbonate) (PTM C) with lithium bis(trifluoromethane sulfonyl)imide (LiTFSI) are prepared by a simple solvent casting method. Although PEC and PTMC have similar chemical structures, they are immiscible and two glass transitions are present in the differential scanning calorimetry (DSC) measurements. Interestingly, these two polymers change to miscible blends with the addition of LiTFSI, and the ionic conductivity increases with increasing lithium salt concentration. The optimum composition of the blend electrolyte is achieved at PEC6 PTMC4 , with a conductivity as high as 10-6 S cm-1 at 50 °C. This value is greater than that for single PEC- and PTMC-based electrolytes. Moreover, the thermal stability of the blend-based electrolytes is improved as compared to PEC-based electrolytes. It is clear that the interaction between CO groups and Li+ gives rise to a compatible amorphous phase of PEC and PTMC.

Association between platelet function and recurrent ischemic vascular events after TIA and minor stroke
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Platelet activation and aggregation play an important role in the pathological and physiological processes of recurrent ischemic vascular events in stroke patients. The purpose of this study is to determine the association between platelet function measured in the acute period and recurrent ischemic vascular events in patients with transient ischemic attack (TIA) or minor stroke. A total of 417 patients who were within the 24-hour period of clopidogrel-aspirin therapy after onset of a minor stroke or high-risk transient ischemic attack according to the Clopidogrel in High-risk patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial were included in this study. The platelet aggregation ratio was detected using a method of continuous platelet counting; patients underwent CYP2C19 genotyping, and the baseline data were recorded. The patients underwent a 6-month follow-up period during which the recurrent ischemic vascular events were observed. Logistic regression analysis was performed to obtain the risk factors for recurrent ischemic vascular events. The number of patients with recurrent ischemic events who had an arachidonic acid-induced maximum platelet aggregation ratio (MAR-AA) (aspirin 100 mg) (31.85 ± 12.86 vs. 26.71 ± 12.44, p = 0.007) and adenosine diphosphate-induced maximum platelet aggregation ratio (MAR-ADP) after the administration of 75 mg clopidogrel for 12 ± 2 days (65.82 ± 10.72 vs. 53.10 ± 12.98, p < 0.001) was significantly higher compared with the no ischemic vascular event group. Multivariate logistic regression analyses showed that being a carrier of the CYP2C19 loss-of-function (LOF) allele (OR = 2.308, 95% CI: 1.087 ~ 4.901, p = 0.029) as well as the MAR-AA (aspirin 100 mg) (OR = 1.028, 95% CI: 1.006  ~  1.052, p = 0.014) and MAR-ADP after the administration of 75 mg clopidogrel (OR = 1.067, 95% CI: 1.037 ~ 1.095, p < 0.001) were risk factors for ischemic vascular events. The MAR-ADP after the administration of 75 mg clopidogrel was significantly higher in patients who were carriers of the CYP2C19 (LOF) allele compared with non-carriers (57.53 ± 13.32 vs. 50.86 ± 12.55, p < 0.001), and no significant differences between the CYP2C19 LOF allele carriers and non-carriers in the MAR-ADP were detected after the administration of 300 mg clopidogrel (37.18 ± 11.36 vs. 35.86 ± 12.49, p = 0.264). Being a carrier of the CYP2C19 LOF allele has a significant influence on clopidogrel response. Platelet function is closely related to recurrent ischemic vascular events in acute minor stroke or TIA patients.
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Non-intervention observation: Dynamic evolution laws of inflammatory response in necrotizing enterocolitis.

The pathogenesis of necrotizing enterocolitis (NEC) is not well understood but immunological factors are thought to be key determinants of the disease appearance and its prognosis. During the course of the present study, different groups of newborn infants were observed and tested, to obtain an accurate image of values of pro- and anti-inflammatory cytokines at the onset, development and progression of neonatal NEC and to compare the values to those obtained during normal healthy development. All the infants in the study received standard medical treatment as appropriate. Initially, all the low birth weight premature infants born between June, 2014 and June, 2015 were tested on days 1, 3, 7, 10, 14, and 21 after birth, to obtain serum values of platelet activating factor (PAF), interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α) and IL-10. In total, 150 low birth weight premature infants were included, and the incidence of NEC was 6.67% (10/150). For the comparison studies, 10 premature NEC infants of low birth weight, 15 premature normal infants, and 15 full-term normal infants born during the same period were enrolled in the study. The serum values of PAF, IL-1, TNF-α and IL-10 for these infants were detected on the same days after birth. PAF, IL-1 and TNF-α levels began to increase on days 1-3 after birth in premature infants, reached a peak on days 7-10, and declined to normal levels on days 14-21. Comparison differences in premature and full-term infants were statistically significant (P<0.01). Interleukin-10 began to increase on days 7-10 after birth in premature infants and reached a peak on days 14-21. Comparisons among premature and full-term infants at the given time points showed the differences were also statistically significant (P<0.01). The differences in values of the above inflammatory cytokines in the infants that died and the values in the survivors were not statistically significant (P>0.05). In conclusion, pro-inflammatory factors PAF, IL-1, TNF-α and anti-inflammatory factor IL-10 may be important in the pathogenesis of NEC, and monitoring their levels in blood can be useful in the prediction of the occurrence of disease. Nevertheless, these levels are not useful as prognostic markers.

LncRNA-HOTAIR promotes TNF-α production in cardiomyocytes of LPS-induced sepsis mice by activating NF-κB pathway.

BACKGROUND: Mounting studies have illustrated an important role of HOTAIR in cancer progress, but few studies have reported its function in cardiac disease, including cardiac-associated sepsis. This study aimed to investigate the function of HOTAIR in sepsis, involving its association with the level of tumor necrosis factor-alpha (TNF-α), an important inducer of myocardial dysfunction during LPS-induced sepsis. METHODS: Sepsis mice model was established by LPS administration, and myocardial dysfunction was evaluated with hemodynamic parameters. HOTAIR expression in isolated cardiomyocytes and TNF-α production in the circulation were detected, as well as the protein levels of phosphorylated p65. HL-1 cells were subjected to LPS treatment in vitro for functional studies, including luciferase report assays for NF-κB activity. RESULTS: HOTAIR expression was significantly upregulated in cardiomyocytes from sepsis mice, in line with increased TNF-α production and p65 phosphorylation, while similar results were also observed in LPS treated HL-1 cells, which was then reversed by HOTAIR interference. Functional studies demonstrated that HOTAIR showed positive regulation on p65 phosphorylation and NF-κB activation, while HOTAIR-induced TNF-α production was repressed by NF-κB inhibitor. Further in vivo studies confirmed that HOTAIR silence can improve cardiac function of sepsis mice, and markedly decreased TNF-α production in the circulation. CONCLUSION: HOTAIR upregulation in cardiomyocytes of LPS-induced sepsis mice promoted TNF-α production in the circulation by activating NF-κB, involving the phosphorylation of NF-κB p65 subunit. Moreover, HOTAIR silence preserved cardiac function of sepsis mice during LPS-induced sepsis.

Biomarkers of Renal Function in Type 2 Diabetic Patients with Cognitive Impairment.

Kidney disease is associated with cognitive impairment in studies of nondiabetic adults. We examined the cross-sectional relation between three measures of renal function and cognitive impairment (CI) in type 2 diabetic patients. A total of 357 patients with type 2 diabetes were prospectively enrolled. There were 108 patients with CI and 249 patients without CI (control). We calculated the urinary albumin/creatinine ratio (UACR) from morning spot urine and the estimated glomerular filtration rate (eGFR) in serum samples. Serum Cystatin C (Cys C) was measured with an automated particle-enhanced turbidimetric immunoassay. UACR and Cystatin C levels were significantly higher in patients with CI than those without CI (P<0.001), and the eGFR was lower in patients with CI than those without (P=0.003). A logistic regression analysis indicates that kidney impairment biomarkers levels were significantly associated with an increased risk of CI after adjustment for age and gender. The OR of each kidney biomarker (eGFR, UACR, Cystatin C) for CI status was 1.78 (0.89-3.27), 2.36 (1.29-4.42), and 2.77 (1.36-5.97), respectively. Among three kidney biomarkers (eGFR, UACR, Cystatin C), only elevated serum Cystatin C was associated with increased risk of CI in type 2 diabetic patients, with an OR of 1.42 (1.25-4.24) after additional adjustment for duration of diabetes, hypertension, hyperlipidemia, hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein (Hs-CRP), intima-media thickness (IMT), ankle brachial index (ABI), and brachial-ankle pulse wave velocity (ba-PWV). Furthermore, combination of conventional risk factors and Cystatin C levels exhibited a fair diagnostic value for CI, with an area under the curve (AUC) of 0.91. Among three kidney impairment biomarkers (eGFR, UACR, Cystatin C), only elevated serum Cystatin C was associated with increased risk of CI in type 2 diabetic patients, independent of conventional risk factors. Furthermore, Cystatin C may be a better marker for CI than eGFR and UACR, and exhibited diagnostic value.

Effect of Nonstructural Protein 2 Hypervariable Regions in the Replication of Porcine Reproductive and Respiratory Syndrome Virus in Marc-145 Cells.

BACKGROUND: Highly pathogenic (HP) porcine reproductive and respiratory syndrome virus (PRRSV) causes prolonged high fever, red discoloration of the body, blue ears and a high mortality. Previously, we found that the PRRSV vaccine strain TJM contained a deletion of 120 amino acids (aa 628-747) in nonstructural protein 2 (Nsp2). We aimed to explore the replication features of PRRSV after adding the transiently expressed product of these 120 aa in vitro. METHODS: We constructed seven eukaryotic expression plasmids containing different parts of the 120-aa sequence, transfected them into Marc-145 cells and then inoculated the cells with 103 TCID50 TJM per well. We detected virus replication at mRNA and protein level by real-time RT-PCR and Western blotting, respectively, and determined the virus titer. RESULTS: The transiently expressed 120 aa and one of its truncated polypeptides inhibited PRRSV TJM propagation on Marc-145 cells. The complete 120-aa sequence induced a remarkable decrease in PRRSV replication, causing a reduction in structural protein levels between 36 and 48 h after infection. Additionally, aa 628-727 partly reduced the replication of PRRSV on Marc-145 cells. CONCLUSIONS: The 120 aa from Nsp2, especially aa 628-727, play a negative role in PRRSV TJM proliferation.

Increased plasma levels of phospholipid in Parkinson's disease with mild cognitive impairment.

This study aimed to observe the clinical characteristics and changes in plasma phospholipid (PL) concentrations in Parkinson's disease patients with mild cognitive impairment (PD-MCI), and to investigate the association between these changes and cognitive function to provide a basis for early diagnosis and intervention for PD-MCI patients. Oxidative stress plays an important role in the development and progression of Parkinson's disease (PD). PL, important components in cellular membranes, are critical for the maintenance of cell integrity and function. Lipid peroxidation products are significantly increased in the brains of PD patients. In the present study, plasma PL levels were significantly increased in PD-MCI patients or in PD patients with no cognitive impairment (PD-NCI) compared with controls (p<0.01 and p<0.05, respectively). PL levels were significantly increased in the PD-MCI group compared with PD-NCI patients (p<0.01). There was a negative correlation between plasma PL levels and Montreal cognitive assessment scores (r=-0.542; p<0.001). These findings support the relationship between mild cognitive impairment and membrane injury. The measurement of PL reflects membrane injury in vivo and may be a new useful biomarker for the prognosis of cognitive states in patients with PD.

Associations between biomarkers of renal function with cerebral microbleeds in hypertensive patients.

BACKGROUND: Cerebral microbleeds (CMBs) have been observed in the elderly and have been regarded as a manifestation of small vessel disease (SVD). Cerebral and glomerular SVD may have a common source of pathogenesis because these organs are closely connected through anatomic and hemodynamic similarities. The purpose of this study was to clarify the associations between kidney biomarker levels and CMBs in hypertensive patients. METHODS: The presence and number of CMBs were assessed on susceptibility-weighted imaging. We calculated the urinary albumin/creatinine ratio (UACR) from morning spot urine and the estimated glomerular filtration rate (eGFR) in serum samples. Serum cystatin C (CysC) was measured with an automated particle-enhanced turbidimetric immunoassay. RESULTS: UACR and CysC levels were higher in the patients with CMBs than those without, and the eGFR was lower in the patients with CMBs than those without. A logistic regression analysis indicates that eGFR and UACR were independently associated with the prevalence of deep or infratentorial CMBs. The odds ratio (OR) (95% confidence interval (CI)) of eGFR and UACR was 1.95 (1.37-3.27) and 2.25 (1.66-4.46), respectively. CysC was independently associated with CMBs in both deep or infratentorial and lobar locations. The ORs (95% CI) were 2.59 (1.57-6.22) and 1.57 (1.15-4.85), respectively. Furthermore, CysC exhibited fair diagnostic value for CMBs, with an area under the curve of 0.80. CONCLUSIONS: Kidney biomarker levels are associated with the presence of CMB in hypertensive patients without a history of transient ischemic attack (TIA) or stroke, independent of conventional risk factors, and CysC was a better marker for CMBs than eGFR and UACR.