Integration of caveolin-mediated cytosolic delivery and enzyme-responsive releasing of squalenoyl nanoparticles enhance the anti-cancer efficacy of chidamide in pancreatic cancer.

We explored the potential of overcoming the dense interstitial barrier in pancreatic cancer treatment by enhancing the uptake of hydrophilic chemotherapeutic drugs. In this study, we synthesized the squalenoyl-chidamide prodrug (SQ-CHI), linking lipophilic squalene (SQ) with the hydrophilic antitumor drug chidamide (CHI) through a trypsin-responsive bond. Self-assembled nanoparticles with sigma receptor-bound aminoethyl anisamide (AEAA) modification, forming AEAA-PEG-SQ-CHI NPs (A-C NPs, size 116.6 ± 0.4 nm), and reference nanoparticles without AEAA modification, forming mPEG-SQ-CHI NPs (M-C NPs, size 88.3 ± 0.3 nm), were prepared. A-C NPs exhibited significantly higher in vitro CHI release (74.7 %) in 0.5 % trypsin medium compared to release (20.2 %) in medium without trypsin. In vitro cell uptake assays revealed 3.6 and 2.3times higher permeation of A-C NPs into tumorspheres of PSN-1/HPSC or CFPAC-1/HPSC, respectively, compared to M-C NPs. Following intraperitoneal administration to subcutaneous tumor-bearing nude mice, the A-C NPs group demonstrated significant anti-pancreatic cancer efficacy, inducing cancer cell apoptosis and inhibiting proliferation in vivo. Mechanistic studies revealed that AEAA surface modification on nanoparticles promoted intracellular uptake through caveolin-mediated endocytosis. This nanoparticle system presents a novel therapeutic approach for pancreatic cancer treatment, offering a delivery strategy to enhance efficacy through improved tumor permeation, trypsin-responsive drug release, and specific cell surface receptor-mediated intracellular uptake.

Carboxymethylated Rhizoma alismatis polysaccharides reduces the risk of calcium oxalate stone formation by reducing cellular inflammation and oxidative stress.

This study aims to elucidate the mechanism and potential of Rhizoma alismatis polysaccharides (RAPs) in preventing oxidative damage to human renal proximal tubule epithelial cells. The experimental approach involved incubating HK-2 cells with 100 nm calcium oxalate monohydrate for 24 h to establish a cellular injury model. Protection was provided by RAPs with varying carboxyl group contents: 3.57%, 7.79%, 10.84%, and 15.33%. The safeguarding effect of RAPs was evaluated by analyzing relevant cellular biochemical indicators. Findings demonstrate that RAPs exhibit notable antioxidative properties. They effectively diminish the release of reactive oxygen species, lactate dehydrogenase, and malondialdehyde, a lipid oxidation byproduct. Moreover, RAPs enhance superoxide dismutase activity and mitochondrial membrane potential while attenuating the permeability of the mitochondrial permeability transition pore. Additionally, RAPs significantly reduce levels of inflammatory factors, including NLRP3, TNF-α, IL-6, and NO. This reduction corresponds to the inhibition of overproduced pro-inflammatory mediator nitric oxide and the caspase 3 enzyme, leading to a reduction in cellular apoptosis. RAPs also display the ability to suppress the expression of the HK-2 cell surface adhesion molecule CD44. The observed results collectively underscore the substantial anti-inflammatory and anti-apoptotic potential of all four RAPs. Moreover, their capacity to modulate the expression of cell surface adhesion molecules highlights their potential in inhibiting the formation of kidney stones. Notably, RAP3, boasting the highest carboxyl group content, emerges as the most potent agent in this regard.

OTUB1/NDUFS2 axis promotes pancreatic tumorigenesis through protecting against mitochondrial cell death.

Pancreatic cancer is one of the most fatal cancers in the world. A growing number of studies have begun to demonstrate that mitochondria play a key role in tumorigenesis. Our previous study reveals that NDUFS2 (NADH: ubiquinone oxidoreductase core subunit S2), a core subunit of the mitochondrial respiratory chain complex I, is upregulated in Pancreatic adenocarcinoma (PAAD). However, its role in the development of PAAD remains unknown. Here, we showed that NDUFS2 played a critical role in the survival, proliferation and migration of pancreatic cancer cells by inhibiting mitochondrial cell death. Additionally, protein mass spectrometry indicated that the NDUFS2 was interacted with a deubiquitinase, OTUB1. Overexpression of OTUB1 increased NDUFS2 expression at the protein level, while knockdown of OTUB1 restored the effects in vitro. Accordingly, overexpression and knockdown of OTUB1 phenocopied those of NDUFS2 in pancreatic cancer cells, respectively. Mechanically, NDUFS2 was deubiquitinated by OTUB1 via K48-linked polyubiquitin chains, resulted in an elevated protein stability of NDUFS2. Moreover, the growth of OTUB1-overexpressed pancreatic cancer xenograft tumor was promoted in vivo, while the OTUB1-silenced pancreatic cancer xenograft tumor was inhibited in vivo. In conclusion, we revealed that OTUB1 increased the stability of NDUFS2 in PAAD by deubiquitylation and this axis plays a pivotal role in pancreatic cancer tumorigenesis and development.

Targeted inhibition of the PI3K/AKT/mTOR pathway by (+)-anthrabenzoxocinone induces cell cycle arrest, apoptosis, and autophagy in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC), characterized by low survival rates and a high recurrence rate, is a major cause of cancer-related mortality. Aberrant activation of the PI3K/AKT/mTOR signaling pathway is a common driver of NSCLC. Within this study, the inhibitory activity of (+)-anthrabenzoxocinone ((+)-ABX), an oxygenated anthrabenzoxocinone compound derived from Streptomyces, against NSCLC is demonstrated for the first time both in vitro and in vivo. Mechanistically, it is confirmed that the PI3K/AKT/mTOR signaling pathway is targeted and suppressed by (+)-ABX, resulting in the induction of S and G2/M phase arrest, apoptosis, and autophagy in NSCLC cells. Additionally, the augmentation of intracellular ROS levels by (+)-ABX is revealed, further contributing to the inhibition of the signaling pathway and exerting inhibitory effects on tumor growth. The findings presented in this study suggest that (+)-ABX possesses the potential to serve as a lead compound for the treatment of NSCLC.

Effects of web neonatal intensive care unit diaries on the mental health, quality of life, sleep quality, care ability, and hormone levels of parents of preterm infants in the neonatal intensive care unit: A randomized controlled trial.

OBJECTIVE: To examine the effects of web neonatal intensive care unit diaries on the mental health, quality of life, sleep quality, care ability, and hormone levels of parents of preterm infants in the neonatal intensive care unit. DESIGN: Prospective randomized controlled parallel-group clinical trial. SETTING: Maternal and Child Health Hospital, Fujian, China. METHODS: The control group received routine neonatal intensive care unit care, while the intervention group received a web neonatal intensive care unit diary based on routine care. Outcomes, including anxiety, depression, and post-traumatic stress disorder symptoms, quality of life, sleep quality, care ability, and cortisol and melatonin levels, were evaluated at T1 (Time 1, before the intervention), T2 (Time 2, immediately after the intervention), and T3 (Time 3, 1 month after the intervention). RESULTS: Seventy pairs of parents of preterm infants in the neonatal intensive care unit were randomly allocated to two groups: intervention (n = 35) and control (n = 35). The anxiety scores in the intervention group were significantly lower at T2 and T3 than those in the control group (P < 0.001). The care ability scores in the intervention group were significantly higher at T2 and T3 (P < 0.001). The prevalence of post-traumatic stress disorder at T3 was significantly different between the groups (P = 0.040). No significant differences were observed in the quality of life or sleep quality between the groups at T2 and T3 (P > 0.05). No significant differences were observed in cortisol and melatonin levels between the groups (P > 0.05). CONCLUSIONS: Web neonatal intensive care unit diaries effectively relieved anxiety symptoms, reduced the prevalence of post-traumatic stress disorder, and enhanced the care abilities of parents of preterm infants in the neonatal intensive care unit. IMPLICATIONS FOR CLINICAL PRACTICE: Web neonatal intensive care unit diary can be considered in clinical practice as a convenient psychological intervention method, especially among parents of preterm infants in the neonatal intensive care unit.

Multifaceted roles of Meg3 in cellular senescence and atherosclerosis.

BACKGROUND AND AIMS: Long noncoding RNAs are involved in the pathogenesis of atherosclerosis. As long noncoding RNAs maternally expressed gene 3 (Meg3) prevents cellular senescence of hepatic vascular endothelium and obesity-induced insulin resistance, we decided to examine its role in cellular senescence and atherosclerosis. METHODS AND RESULTS: By analyzing our data and human and mouse data from the Gene Expression Omnibus database, we found that Meg3 expression was reduced in humans and mice with cardiovascular disease, indicating its potential role in atherosclerosis. In Ldlr-/- mice fed a Western diet for 12 weeks, Meg3 silencing by chemically modified antisense oligonucleotides attenuated the formation of atherosclerotic lesions by 34.9% and 20.1% in male and female mice, respectively, revealed by en-face Oil Red O staining, which did not correlate with changes in plasma lipid profiles. Real-time quantitative PCR analysis of cellular senescence markers p21 and p16 revealed that Meg3 deficiency aggravates hepatic cellular senescence but not cellular senescence at aortic roots. Human Meg3 transgenic mice were generated to examine the role of Meg3 gain-of-function in the development of atherosclerosis induced by PCSK9 overexpression. Meg3 overexpression promotes atherosclerotic lesion formation by 29.2% in Meg3 knock-in mice independent of its effects on lipid profiles. Meg3 overexpression inhibits hepatic cellular senescence, while it promotes aortic cellular senescence likely by impairing mitochondrial function and delaying cell cycle progression. CONCLUSIONS: Our data demonstrate that Meg3 promotes the formation of atherosclerotic lesions independent of its effects on plasma lipid profiles. In addition, Meg3 regulates cellular senescence in a tissue-specific manner during atherosclerosis. Thus, we demonstrated that Meg3 has multifaceted roles in cellular senescence and atherosclerosis.

Tetraphenylethene-modified polysiloxanes: Synthesis, AIE properties and multi-stimuli responsive fluorescence.

Herein, polysiloxane-based aggregation-induced emission (AIE) polymers and rubbers were prepared which display interesting multi-stimuli responsive fluorescence. TPE-modified polydimethylsiloxanes (PDMS-TPE) as polysiloxane-based AIE polymers were synthesized through Heck reaction of bromo-substituted tetraphenylethene (TPE-Br) and vinyl polysiloxanes. As expected, TPE moiety endows the modified polysiloxane with typical AIE behavior. However, limited by the long polymer chains, the aggregation process of PDMS-TPE shows obvious differences compared with the small molecule TPE-Br. The fluorescence of PDMS-TPE in THF/H2O starts to increase when the H2O fraction (fw) is 70% while TPE-Br is nearly non-luminous until the fw is up to 99%. The fluorescence intensity ratio (I/I0) of PDMS-TPE in the aggregated state and dispersed state is over 1300, greater than that of TPE-Br (I/I0 = 380). More importantly, the exceptional thermal motion of Si-O-Si chains and AIE characteristic of TPE moiety work together, enabling PDMS-TPE to show specific temperature-dependent fluorescence with a wider response range of room temperature to 190°C, which is distinguished from TPE-Br. And such fluorescence responsiveness possess good fatigue-resistance. Furthermore, fluorescent silicone rubbers, r-PDMS-TPE were prepared by using PDMS-TPE as additive of the base gum. They display interesting solvent-controllable fluorescence and higher tensile strength (4.42 MPa) than the control sample without TPE component (1.96 MPa). Notably, a unique stretching-enhanced emission (SEE) phenomenon is observed from these TPE-modified silicone rubbers. When being stretched, the rubbers' fluorescent emission intensity could increase by 143%.

A disposable paper-based electrochemical biosensor decorated by electrospun cellulose acetate nanofibers for highly sensitive bio-detection.

Paper-based electrochemical sensors have the characteristics of flexibility, biocompatibility, environmental protection, low cost, wide availability, and hydropathy, which make them very suitable for the development and application of biological detection. This work proposes electrospun cellulose acetate nanofiber (CA NF)-decorated paper-based screen-printed (PBSP) electrode electrochemical sensors. The CA NFs were directly collected on the PBSP electrode through an electrospinning technique at an optimized voltage of 16 kV for 10 min. The sensor was functionalized with different bio-sensitive materials for detecting different targets, and its sensing capability was evaluated by CV, DPV, and chronoamperometry methods. The test results demonstrated that the CA NFs enhanced the detection sensitivity of the PBSP electrode, and the sensor showed good stability, repeatability, and specificity (p < 0.01, N = 3). The electrochemical sensing of the CA NF-decorated PBSP electrode exhibited a short detection duration of ∼5-7 min and detection ranges of 1 nmol mL-1-100 µmol mL-1, 100 fg mL-1-10 µg mL-1, and 1.5 × 102-106 CFU mL-1 and limits of detection of 0.71 nmol mL-1, 89.1 fg mL-1, and 30 CFU mL-1 for glucose, Ag85B protein, and E. coli O157:H7, respectively. These CA NF-decorated PBSP sensors can be used as a general electrochemical tool to detect, for example, organic substances, proteins, and bacteria, which are expected to achieve point-of-care testing of pathogenic microorganisms and have wide application prospects in biomedicine, clinical diagnosis, environmental monitoring, and food safety.

Retention behavior of nucleosides and nucleobases on a 3 µm undecylenic acid-functionalized silica column in per aqueous liquid chromatography and hydrophilic interaction liquid chromatography separation modes.

A 3 µm undecylenic acid-functionalized stationary phase (UAS) was prepared for the separation of nucleosides and nucleobases using per aqueous liquid chromatography (PALC) and hydrophilic interaction liquid chromatography (HILIC). The retention behaviors of nucleosides and nucleobases in PALC and HILIC modes were explored by adjusting parameters such as water content, buffer concentration, pH of the mobile phase and column temperature. The experimental data and separation chromatogram demonstrated that PALC could provide retention comparable to that of HILIC for nucleosides and nucleobases. Comparative studies using diluted adenosine solutions evaluated theoretical plates and peak shape for the same retention factors (between 0.25 and 5.0) in PALC and HILIC. There was no buffer component in the mobile phases used to operate the comparisons. HILIC mode is more efficient for adenosine than PALC mode at low retention factors. It's the exact opposite phenomenon for high retention factors. It is proposed that the mass transfer of adenosine between the UAS, the water-rich layer and the ACN-rich mobile phase in HILIC is relatively slow. Given the significant use of toxic ACN in HILIC, PALC emerges as a safer and more effective alternative for separating nucleosides and nucleobases.

Current landscape of preoperative neoadjuvant therapies for initial resectable colorectal cancer liver metastasis.

Colorectal cancer liver metastasis (CRLM) presents a clinical challenge, and optimizing treatment strategies is crucial for improving patient outcomes. Surgical resection, a key element in achieving prolonged survival, is often linked to a heightened risk of recurrence. Acknowledging the potential benefits of preoperative neoadjuvant chemotherapy in managing resectable liver metastases, this approach has gained attention for its role in tumor downsizing, assessing biological behavior, and reducing the risk of postoperative recurrence. However, the use of neoadjuvant chemotherapy in initially resectable CRLM sparks ongoing debates. The balance between tumor reduction and the risk of hepatic injury, coupled with concerns about delaying surgery, necessitates a nuanced approach. This article explores recent research insights and draws upon the practical experiences at our center to address critical issues regarding considerations for initially resectable cases. Examining the criteria for patient selection and the judicious choice of neoadjuvant regimens are pivotal areas of discussion. Striking the right balance between maximizing treatment efficacy and minimizing adverse effects is imperative. The dynamic landscape of precision medicine is also reflected in the evolving role of gene testing, such as RAS/BRAF and PIK3CA, in tailoring neoadjuvant regimens. Furthermore, the review emphasizes the need for a multidisciplinary approach to navigate the complexities of CRLM. Integrating technical expertise and biological insights is crucial in refining neoadjuvant strategies. The management of progression following neoadjuvant chemotherapy requires a tailored approach, acknowledging the diverse biological behaviors that may emerge. In conclusion, this review aims to provide a comprehensive perspective on the considerations, challenges, and advancements in the use of neoadjuvant chemotherapy for initially resectable CRLM. By combining evidence-based insights with practical experiences, we aspire to contribute to the ongoing discourse on refining treatment paradigms for improved outcomes in patients with CRLM.

Downregulation of miR-337-3p in hypoxia/reoxygenation neuroblastoma cells increases KCTD11 expression.

Neurodegeneration is linked to the progressive loss of neural function and is associated with several diseases. Hypoxia is a hallmark in many of these diseases, and several therapies have been developed to treat this disease, including gene expression therapies that should be tightly controlled to avoid side effects. Cells experiencing hypoxia undergo a series of physiological responses that are induced by the activation of various transcription factors. Modulation of microRNA (miRNA) expression to alter transcriptional regulation has been demonstrated to be beneficial in treating multiple diseases, and in this study, we therefore explored potential miRNA candidates that could influence hypoxia-induced nerve cell death. Our data suggest that in mouse neuroblasts Neuro-2a cells with hypoxia/reoxygenation (H/R), miR-337-3p is downregulated to increase the expression of Potassium channel tetramerization domain containing 11 (KCTD11) and subsequently promote apoptosis. Here, we demonstrate for the first time that KCTD11 plays a role in the cellular response to hypoxia, and we also provide a possible regulatory mechanism by identifying the axis of miR-337-3p/KCTD11 as a promising candidate modulator of nerve cell survival after H/R exposure.

The application value of 3D ASL in evaluating the effectiveness of stent implantation for vertebrobasilar artery stenosis.

OBJECTIVE: To evaluate the effect of stent implantation for vertebrobasilar artery stenosis，by using 3D arterial spin labeling (3D ASL) technique. METHODS: A retrospective analysis was conducted on the clinical and 3D ASL data of 48 patients who underwent vertebral-basilar artery stenting. Post-labeling delay times (PLD) of 1.5 s and 2.5 s were chosen, and the average regional cerebral blood flow (rCBF) values were measured in nine brain regions of the posterior circulation: bilateral thalamus, bilateral occipital lobes, bilateral cerebellar hemispheres, midbrain, pons, and medulla. The 48 patients were divided into two groups based on the presence or absence of acute ischemic stroke in the posterior cerebral circulation region detected by diffusion-weighted imaging (DWI). The preoperative and postoperative rCBF results were statistically analyzed. RESULTS: In the infarct group, there were significant increases in rCBF values of all nine brain regions at both PLD = 1.5 s and 2.5 s postoperatively compared to preoperatively. At PLD = 1.5 s, statistically significant differences in rCBF values between the preoperative and postoperative periods were found in the right thalamus, left cerebellum, midbrain, and pons regions (P < 0.05). At PLD = 2.5 s, statistically significant differences in rCBF values between the preoperative and postoperative periods were observed in the left occipital lobe, right cerebellum, midbrain, and pons regions (P < 0.05). When analyzing the rCBF values of the brain regions with recent infarcts in the infarct group, there was a significant increase in postoperative rCBF values compared to preoperative values (P < 0.05). After excluding the data from brain regions with recent infarcts, the CBF values in the remaining brain regions were also increased postoperatively, and some brain regions showed statistically significant differences in rCBF values between the preoperative and postoperative periods (P < 0.05). In the non-infarct group, there were no statistically significant differences in the preoperative and postoperative rCBF values in all brain regions at both PLD = 1.5 s and 2.5 s (P > 0.05). CONCLUSION: The application of 3D ASL technology shows significant value in assessing the surgical efficacy of vertebral-basilar artery stenting, especially in patients with acute posterior circulation infarction.

Digital health literacy and associated factors among internet users from China: a cross-sectional study.

BACKGROUND: As the internet develops and 5G technology becomes increasingly prominent, the internet has become a major source of health-related information. Increasingly, people use the internet to find health-related information, and digital health literacy is now a set of essential capabilities to improve their health in the digital era. However, little is known about the factors that influencing digital health literacy. This study aimed to assess digital health literacy scores and identify its influencing factors among internet users in China. Additionally, this study explored the participant's actual skills using an additional set of performance-based items from the Digital Health Literacy Instrument (DHLI). METHODS: An online cross-sectional study was conducted in August 2022. Participants aged ≥18 years were recruited to complete the survey. Data were collected using the Chinese revised version of the DHLI, the self-reported internet use questionnaire, and the sociodemographic questionnaire. We conducted multivariate linear regression analyses to explore the relationships among the sociodemographic variables, behavior of internet use, and the digital health literacy scores. RESULTS: In total, 702 participants completed the survey. The mean DHLI score was 2.69 ± 0.61. Multivariate linear regression analyses showed that the age groups 35-49 (ß = - 0.08, P = 0.033), 50-64 (ß = - 0.161, P < 0.001), and ≥ 65 (ß = - 0.138, P < 0.001) were negatively associated with DHL scores. However, education level, including bachelor's or associate degree (ß = 0.255, P = 0.002) and master's degree and above (ß = 0.256, P < 0.001), frequency of health-related Internet usage (ß = 0.192, P < 0.001), the number of digital devices used (ß = 0.129, P = 0.001), and OHISB (ß = 0.103, P = 0.006) showed a positive relationship with DHL scores. CONCLUSIONS: The study findings demonstrate that age, educational levels, number of technological devices used, and greater use of the web for health information were independently associated with DHL scores. Healthcare providers should consider providing training programs tailored to specific sociodemographic factors to improve the ability that find and use accurate information online to meet digital health services, which contributes to enhance their self-management and reduce health disparities.

The recent advance and prospect of natural source compounds for the treatment of heart failure.

Heart failure is a continuously developing syndrome of cardiac insufficiency caused by diseases, which becomes a major disease endangering human health as well as one of the main causes of death in patients with cardiovascular diseases. The occurrence of heart failure is related to hemodynamic abnormalities, neuroendocrine hormones, myocardial damage, myocardial remodeling etc, lead to the clinical manifestations including dyspnea, fatigue and fluid retention with complex pathophysiological mechanisms. Currently available drugs such as cardiac glycoside, diuretic, angiotensin-converting enzyme inhibitor, vasodilator and ß receptor blocker etc are widely used for the treatment of heart failure. In particular, natural products and related active ingredients have the characteristics of mild efficacy, low toxicity, multi-target comprehensive efficacy, and have obvious advantages in restoring cardiac function, reducing energy disorder and improving quality of life. In this review, we mainly focus on the recent advance including mechanisms and active ingredients of natural products for the treatment of heart failure, which will provide the inspiration for the development of more potent clinical drugs against heart failure.

8-shogaol derived from dietary ginger alleviated acute and inflammatory pain by targeting TRPV1.

Ginger, a well-known spice plant, has been used widely in medicinal preparations for pain relief. However, little is known about its analgesic components and the underlying mechanism. Here, we ascertained, the efficacy of ginger ingredient 8-Shogaol (8S), on inflammatory pain and tolerance induced by morphine, and probed the role of TRPV1 in its analgesic action using genetic and electrophysiology approaches. Results showed that 8S effectively reduced nociceptive behaviors of mice elicited by chemical stimuli, noxious heat as well as inflammation, and antagonized morphine analgesic tolerance independent on opioid receptor function. Genetic deletion of TRPV1 significantly abolished 8S' analgesia action. Further calcium imaging and patch-clamp recording showed that 8S could specifically activate TRPV1 in TRPV1-expressing HEK293T cells and dorsal root ganglion (DRG) neurons. The increase of [Ca2+]i in DRG was primarily mediated through TRPV1. Mutational and computation studies revealed the key binding sites for the interactions between 8S and TRPV1 included Leu515, Leu670, Ile573, Phe587, Tyr511, and Phe591. Further studies showed that TRPV1 activation evoked by 8S resulted in channel desensitization both in vitro and in vivo, as may be attributed to TRPV1 degradation or TRPV1 withdrawal from the cell surface. Collectively, this work provides the first evidence for the attractive analgesia of 8S in inflammatory pain and morphine analgesic tolerance mediated by targeting pain-sensing TRPV1 channel. 8S from dietary ginger has potential as a candidate drug for the treatment of inflammatory pain.

Transplantation of human neural stem cell prevents symptomatic motor behavior disability in a rat model of Parkinson's disease.

Parkinson's disease (PD) is a ubiquitous brain cell degeneration disease and presents a significant therapeutic challenge. By injecting 6-hydroxydopamine (6-OHDA) into the left medial forebrain bundle, rats were made to exhibit PD-like symptoms and treated by intranasal administration of a low-dose (2 × 105) or high-dose (1 × 106) human neural stem cells (hNSCs). Apomorphine-induced rotation test, stepping test, and open field test were implemented to evaluate the motor behavior and high-performance liquid chromatography was carried out to detect dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin, and 5-hydroxyindole-3-acetic acid in the striatum of rats. Animals injected with 6-OHDA showed significant motor function deficits and damaged dopaminergic system compared to the control group, which can be restored by hNSCs treatment. Treatment with hNSCs significantly increased the tyrosine hydroxylase-immunoreactive cell count in the substantia nigra of PD animals. Moreover, the levels of neurotransmitters exhibited a significant decline in the striatum tissue of animals injected with 6-OHDA when compared to that of the control group. However, transplantation of hNSCs significantly elevated the concentration of DA and DOPAC in the injured side of the striatum. Our study offered experimental evidence to support prospects of hNSCs for clinical application as a cell-based therapy for PD.

Relation between LRG1 and CD4+ T cells, cognitive impairment and neurological function in patients with acute ischemic stroke.

Objective: To assess the relationship between LRG1 and CD4+ T cells, cognitive impairment and neurological function in acute ischemic stroke (AIS). Methods: Plasma LRG1 was detected by ELISA in 175 patients with AIS at baseline, day (D) 1, D7, month (M) 1 and M3. Results: LRG1 was negatively related to Th2 and Treg cells and positively linked to Th17 (all p < 0.05). LRG1 increased from baseline to D1, then decreased until M3 (p < 0.001). LRG1 at each assessment point was increased in patients with cognitive impairment or poor neurological function at M3 versus those without (all p < 0.05). Conclusion: LRG1 is linked to decreased Th2 and Tregs, increased Th17, cognitive impairment and nonideal neurological function recovery in patients with AIS.

Long-term repetitive transcranial direct current stimulation in patients with disorders of consciousness: a preliminary study.

OBJECTIVES: To investigate the effects of long-term repetitive transcranial direct current stimulation on patients with DOC in the subacute phase. METHODS: In a randomized, double-blind, controlled study, 33 patients were randomly assigned to the active or sham group, and 28 patients completed the study. Patients in the active group received anodal stimulation over the DLPFC, while patients in the sham group received placebo stimulation (20 min/day, 5 days/week, for 4 weeks). The level of consciousness among patients was assessed with the Coma Recovery Scale-Revised (CRS-R) at baseline and at the end of every week from the first to the fourth week. RESULTS: The CRS-R scores of both the active and sham groups showed a consistent increasing trend over time; however, the treatment effect of the active group was better than that of the sham group. In addition, there was a statistically significant difference in the total CRS-R score between the two groups at weeks 1, 2, 3 and 4. Moreover, 10 patients (71.4%) in the active group and 3 patients (21.4%) in the sham group were regarded as responders. CONCLUSION: Long-term tDCS could improve the level of consciousness of patients with DOC in the subacute stage.

Slow-wave sleep and REM sleep without atonia predict motor progression in Parkinson's disease.

BACKGROUND: Growing evidence supports the potential role of sleep in the motor progression of Parkinson's disease (PD). Slow-wave sleep (SWS) and rapid eye movement (REM) sleep without atonia (RWA) are important sleep parameters. The association between SWS and RWA with PD motor progression and their predictive value have not yet been elucidated. METHODS: We retro-prospectively analyzed clinical and polysomnographic data of 136 patients with PD. The motor symptoms were assessed using Unified Parkinson's Disease Rating Scale Part III (UPDRS III) at baseline and follow-up to determine its progression. Partial correlation analysis was used to explore the cross-sectional associations between slow-wave energy (SWE), RWA and clinical symptoms. Longitudinal analyses were performed using Cox regression and linear mixed-effects models. RESULTS: Among 136 PD participants, cross-sectional partial correlation analysis showed SWE decreased with the prolongation of the disease course (P = 0.046), RWA density was positively correlated with Hoehn & Yahr (H-Y) stage (tonic RWA, P < 0.001; phasic RWA, P = 0.002). Cox regression analysis confirmed that low SWE (HR = 1.739, 95% CI = 1.038-2.914; P = 0.036; FDR-P = 0.036) and high tonic RWA (HR = 0.575, 95% CI = 0.343-0.963; P = 0.032; FDR-P = 0.036) were predictors of motor symptom progression. Furthermore, we found that lower SWE predicted faster rate of axial motor progression (P < 0.001; FDR-P < 0.001) while higher tonic RWA density was associated with faster rate of rigidity progression (P = 0.006; FDR-P = 0.024) using linear mixed-effects models. CONCLUSIONS: These findings suggest that SWS and RWA might represent markers of different motor subtypes progression in PD.