The role of mechanosensor Piezo1 in bone homeostasis and mechanobiology.

Bones and articular cartilage are important load-bearing tissues. The fluid flow inside the bone cells and cell interaction with the extracellular matrix serve as the mechanical cues for bones and joints. Piezo1 is an ion channel found on the cell surface of many cell types, including osteocytes and chondrocytes. It is activated in response to mechanical stimulation, which subsequently mediates a variety of signaling pathways in osteoblasts, osteocytes, and chondrocytes. Piezo1 activation in osteoblastic cells positively regulates osteogenesis, while its activation in joints mediates cartilage degradation. This review focuses on the most recent research on Piezo1 in bone development and regeneration.

Chromosome-level genome assembly of sea scallop Placopecten magellanicus provides insights into the genetic characteristics and adaptive evolution of large scallops.

Placopecten magellanicus (Gmelin, 1791), a deep-sea Atlantic scallop, holds significant commercial value as a benthic marine bivalve along the northwest Atlantic coast. Recognizing its economic importance, the need to reconstruct its genome assembly becomes apparent, fostering insights into natural resources and generic breeding potential. This study reports a high-quality chromosome-level genome of P. magellanicus, achieved through the integration of Illumina short read sequencing, PacBio HiFi sequencing, and Hi-C sequencing techniques. The resulting assembly spans 1778 Mb with a scaffold N50 of 86.71 Mb. An intriguing observation arises - the genome size of P. magellanicus surpasses that of its Pectinidae family peers by 1.80 to 2.46 times. Within this genome, 28,111 protein-coding genes were identified. Comparative genomic analysis involving five scallop species unveils the critical determinant of this expanded genome: the proliferation of repetitive sequences recently inserted, contributing to its enlarged size. The landscape of whole genome collinearity sheds light on the relationships among scallop species, enhancing our broader understanding of their genomic framework. This genome provides genomic resources for future molecular biology research on scallops and serves as a guide for the exploration of longevity-related genes in scallops.

Acid sphingomyelinase mediates ferroptosis induced by high glucose via autophagic degradation of GPX4 in type 2 diabetic osteoporosis.

BACKGROUND: Ferroptosis has been implicated in the pathological process of type 2 diabetic osteoporosis (T2DOP), although the specific underlying mechanisms remain largely unknown. This study aimed to clarify the role and possible mechanism of acid sphingomyelinase (ASM)-mediated osteoblast ferroptosis in T2DOP. METHODS: We treated hFob1.19 cells with normal glucose (NG) and different concentrations of high glucose (HG, 26.25 mM, 35 mM, or 43.75 mM) for 48 h. We then measured cell viability and osteogenic function, quantified ferroptosis and autophagy levels, and measured the levels of ASM and ceramide in the cells. To further investigate the specific mechanism, we examined these indicators by knocking down ASM expression, hydroxychloroquine (HCQ) treatment, or N-acetylcysteine (NAC) treatment. Moreover, a T2DOP rat model was induced and microcomputed tomography was used to observe the bone microstructure. We also evaluated the serum levels of iron metabolism-associated factors, ceramide and lipid peroxidation (LPO) and measured the expression of ASM, LC3 and GPX4 in bone tissues. RESULTS: HG inhibited the viability and osteogenic function of osteoblasts by inducing ferroptosis in a concentration-dependent manner. Furthermore, the expression of ASM and ceramide and autophagy levels were increased by HG treatment, and these factors were required for the HG-induced reactive oxygen species (ROS) generation and LPO. Similarly, inhibiting intracellular ROS also reduced HG-induced ASM activation and autophagy. ASM-mediated activation of autophagy was crucial for HG-induced degradation of GPX4, and inhibiting ASM improved osteogenic function by decreasing HG-induced autophagy, GPX4 degradation, LPO and subsequent ferroptosis. We also found that inhibiting ASM could alleviated ferroptosis and autophagy and improved osteogenic function in a T2DOP rat model. CONCLUSION: ASM-mediated autophagy activation induces osteoblast ferroptosis under HG conditions through the degradation of GPX4, providing a novel mechanistic insight into the treatment and prevention of T2DOP.

A novel deletion mutation accompanied by a point mutation in Lamin A/C gene: Screened from a dilated cardiomyopathy family.

BACKGROUND: There are 30%-40% of patients with dilated cardiomyopathy (DCM) having genetic causes, among which Lamin A and C gene (LMNA) mutation is the second most frequent DCM-related mutation, and Lamin A/C may be involved in the pathogenesis of DCM through the regulation of gene transcription or the direct effect of cell structure. Methods: Echocardiography and electrocardiogram were used to diagnose DCM and arrhythmia in a DCM family. Then, linked mutations on LMNA were screened out by high-throughput sequencing and verified by Sanger sequencing in all research individuals. Meanwhile, Human Genome Variation Society (HGVS) and Integrative Genomics Viewer (IGV) were used to analyse the characteristics of the mutated Lamin A/C protein. Finally, mutated-type and wild-type LMNA plasmid was transfected into AC-16 cardiomyocytes with the form of a lentivirus vector, and its effect on nucleus and actin was studied by immunofluorescence detection. RESULTS: In this study, we found a new frame-shifted mutation of LMNA (p.Ser414Alafs*66) linked with another point mutation from a DCM family by using High-throughput sequencing, and this deletion mutation led to a truncation of Lamin A/C. By analysing the clinical characteristics of this DCM family, we found that all DCM patients with arrhythmia were carriers of this co-segregation mutation. In the cytological experiment, we found that the mutated-type transfections showed weaker fluorescent intensities on both actin and cell nucleus. CONCLUSIONS: A co-segregation mutation of LMNA (Point mutation chr1 156107548 c.1712 G>A and truncated frame-shifted mutation chr1 156106086 c.1240delA) was found from a DCM family, and this type of mutation could participate in the pathogenesis of DCM by affecting the expression of actin.

Effect of glucocorticoid for patients with type A aortic dissection undergoing surgical repair with deep hypothermic circulatory arrest: A single-center, retrospective study.

BACKGROUND: Postoperative patients with Type A aortic dissection (TAAD) often experience severe inflammatory responses caused by multiple factors perioperatively. However, the effect of postoperative glucocorticoid (GC) use, which is a potent anti-inflammatory agent, on complications or all-cause mortality is unclear. METHODS: Patients with TAAD who underwent surgical repair requiring deep hypothermic circulatory arrest between January 2020 and December 2021 were included in the study. Characteristics of patients treated with and without GCs were compared. The primary outcome was in-hospital mortality, and a composite secondary outcome was defined as in-hospital death or any major complications. Propensity score matching was used to balance baseline differences between groups. Kaplan-Meier curves were used to compare survival probability. RESULTS: A total of 393 postoperative patients with TAAD were included in the study. Forty of them (10.2%) received GC treatment at a median daily methylprednisolone-equivalent dose of 0.6 mg/kg (0.4-0.7) for a median period of 2 (1-3) days. Patients on GCs had more intraoperative blood transfusions, higher postoperative APACHE II (12 vs 9, p = .004) and SOFA (9 vs 6, p < .001) scores, worse perioperative hepatic, renal and cardiac function. The in-hospital mortality in the matched cohort did not differ between groups [GC n = 11/40 (27.5%) versus Non-GC n = 19/80 (23.8%); p = .661]. CONCLUSIONS: The propensity to use GCs correlated with the critical status of the patient. However, low dose and short-term postoperative GC treatment did not reduce in-hospital mortality rates among patients with TAAD. A more appropriate regimen should be further investigated.

Epileptic EEG Signal Detection Using Variational Modal Decomposition and Improved Grey Wolf Algorithm.

Epilepsy does great harm to the human body, and even threatens human life when it is serious. Therefore, research focused on the diagnosis and treatment of epilepsy holds paramount clinical significance. In this paper, we utilized variational modal decomposition (VMD) and an enhanced grey wolf algorithm to detect epileptic electroencephalogram (EEG) signals. Data were extracted from each patient's preseizure period and seizure period of 200 s each, with every 2 s as a segment, meaning 100 data points could be obtained for each patient's health period as well as 100 data points for each patient's epilepsy period. Variational modal decomposition (VMD) was used to obtain the corresponding intrinsic modal function (VMF) of the data. Then, the differential entropy (DE) and high frequency detection (HFD) of each VMF were extracted as features. The improved grey wolf algorithm is adopted for a selected channel to improve the maximum value of the channel. Finally, the EEG signal samples were classified using a support vector machine (SVM) classifier to achieve the accurate detection of epilepsy EEG signals. Experimental results show that the accuracy, sensitivity and specificity of the proposed method can reach 98.3%, 98.9% and 98.5%, respectively. The proposed algorithm in this paper can be used as an index to detect epileptic seizures and has certain guiding significance for the early diagnosis and effective treatment of epileptic patients.

Effects of microbial community and disease resistance against Vibrio splendidus of Yesso scallop (Patinopecten yessoensis) fed supplementary diets of tussah immunoreactive substances and antimicrobial peptides.

This study was conducted to investigate the effects of dietary supplementation of tussah immunoreactive substances (TIS) and antimicrobial peptides (AMPs) on microbial community and resistance against Vibrio splendidus of Yesso scallop Patinopecten yessoensis. Scallops were fed with the basal diets supplemented with TIS (T group), AMPs (A group), or both of the two (TA group). After the feeding trial, the microbial community changes were evaluated, and the challenge test with V. splendidus was conducted, as well as the immune parameters and digestive enzyme activities were determined. The results revealed that the TA group was more capable of modulating the bacterial community composition of scallops by increasing the potentially beneficial bacteria and suppressing the pathogenic microorganism during the feeding trial. After injection, the cumulative mortality rate in TA group was notably lower than others. In addition, the TA group showed better digestive and immune parameters involved in digestive capacity, phagocyte function, phosphatase-responsiveness, and oxidation resistance. These results collectively confirmed that dietary TIS and AMPs in diet could effectively modulate the microflora structure and improve disease resistance against V. splendidus of scallop, and the positive effects were more obvious when dietary supplementation of them in combination.

Enzymatic Hydrolysis of Defatted Antheraea pernyi (Lepidoptera: Saturniidae) Pupa Protein by Combined Neutral Protease Yield Peptides With Antioxidant Activity.

In this study, peptides were prepared from defatted Antheraea pernyi (Lepidoptera: Saturniidae) pupa protein via hydrolysis with combined neutral proteases. Single-factor tests and response surface methodology (RSM) were used to determine the optimal hydrolysis condition suitable for industrial application. Optimal hydrolysis of the defatted pupa protein was found to occur at an enzyme concentration of 4.85 g/liter, a substrate concentration of 41 g/liter, a hydrolysis temperature of 55°C, and a hydrolysis time of 10 h and 40 min. Under these conditions, the predicted and actual rates of hydrolysis were 45.82% and 45.75%, respectively. Peptides with a molecular weight of less than 2,000 Da accounted for 90.5% of the total peptides generated. Some of the peptides were antioxidant peptides as revealed by sequencing and functional analysis. The antioxidant activity of the mixed peptides was subsequently confirmed by an antioxidant activity assay. The results showed that peptides with high antioxidant activity could be obtained from the hydrolysis of A. pernyi pupa protein.

Long-Term Outcomes of Surgical Treatment for Acute Type-A Aortic Dissection with Coronary Artery Involvement.

The surgical strategies for acute type-A aortic dissection (aTAAD) with coronary artery involvement have been controversial, and its prognosis remains unclear. Thus, in this study, we aim to determine the characteristics, surgical strategies, and prognosis of patients with coronary artery involvement due to aTAAD.Retrospective analysis of 65 consecutive aTAAD patients with coronary artery involvement between September 2005 and January 2012 was performed. The patients were divided into two groups: those treated with aTAAD repair and coronary ostia reimplantation (Neri type-A, group A, n = 37) and those with aTAAD repair and coronary artery bypass grafting (Neri type B and C, group B, n = 28).Overall in-hospital mortality was determined to be 8.1% for group A and 21.4% for group B (P = 0.124). No significant difference was determined between groups A and B in cardiopulmonary bypass time, cross-clamp time, cerebral perfusion time, and hospitalization time. Intensive care unit (ICU) stay was 5.8 ± 7.4 days for group A, whereas it was 12.4 ± 10.6 days for group B (P = 0.009). The morbidity of postoperative temporary and permanent neurological dysfunction was similar between the two groups, while renal and respiratory dysfunction were 8.1% versus 25.0% and 16.2% versus 39.3%, respectively (P = 0.062, P = 0.036). Average follow-up time was 112.0 ± 44.8 months, and survival curves have not shown statistical significance between two groups (P = 0.386).Coronary artery dissection with Neri type B and C in acute TAAD has been associated with higher early death, but comparable long-term survival after discharge. However, combined immediate coronary artery bypass grafting and aortic repair remains a safe, effective, and acceptable approach to these challenging group of patients.

Activation of cannabinoid receptor type 2-induced osteogenic differentiation involves autophagy induction and p62-mediated Nrf2 deactivation.

BACKGROUND: Dysfunction in survival and differentiation of osteoblasts commonly occurs in patients with osteoporosis. Cannabinoid receptor type 2 (CNR2) is a major receptor of endocannabinoid system that is crucial for bone mass homeostasis. Our group prior demonstrated that activation of CNR2 signaling promoted osteogenic differentiation of bone marrow derived mesenchymal stem cells in vitro. Autophagy is reported to participate in osteoblastic differentiation. Whether autophagy is regulated by CNR2-mediated cannabinoid signaling is unknown, and how the autophagy-CNR2 interaction affects osteoblastic differentiation requires further elucidation. METHODS: hFOB 1.19 osteoblasts were treated with CNR2 agonists HU308 (5, 10, 25, 50 or 100 nM) and JWH133 (1, 2, 5, 10 or 20 µM) in presence or absence of autophagy inhibitor 3-Methyladenine (3-MA). The differentiation of hFOB 1.19 cells was determined via evaluating their alkaline phosphatase (ALP) activity and mineralization ability (Alizarin red staining). Alterations in autophagy-related molecules and osteogenic markers were analyzed via real-time PCR and/or immunoblotting assays. RESULTS: hFOB 1.19 cells spontaneously differentiated towards mature osteoblasts under 39 °C, during which CNR2 expression increased, and autophagy was activated. The strongest autophagy flux was observed at 192 h post differentiation─LC3I to LC3II conversion was enhanced and Beclin 1 expression was upregulated considerably, while p62 expression was downregulated. Treatment of HU308 and JWH133 promoted autophagy in a dose-dependent manner, and suppressed mTOR signaling pathway in hFOB 1.19 cells. In CNR2-silenced cells, HU308's and JWH133's effects on autophagy were weakened. HU308 and JWH133 enhanced the ALP activity and mineralization, and upregulated the expression of osteogenic markers, osteopontin and osteocalcin, in hFOB 1.19 cells. Intriguingly, such pro-osteogenic effects induced by CNR2 activation were markedly mitigated by 3-MA. In addition to provoking autophagy, CNR2 agonists also reduced nuclear Nrf2 accumulation and increased Keap1 expression. Further, re-expression of p62 inhibited CNR2 agonists-induced Nrf2 degradation. CONCLUSIONS: Osteogenic differentiation induced by CNR2 signaling activation involves autophagy induction and p62-mediated Nrf2 deactivation.

Inhibiting effect of microRNA-187-3p on osteogenic differentiation of osteoblast precursor cells by suppressing cannabinoid receptor type 2.

Induction of osteoblast differentiation is an effective approach in promoting osteoblastogenesis and bone formation. MicroRNA (miR) is a kind of small regulatory RNA molecules that control both physiological and pathological processes. The purpose of this research was to explore the function of miR-187-3p in proliferation and osteogenic differentiation in human osteoblastic precursor cells (hFOB 1.19). Our results showed a significant promotion of cell proliferation by miR-187-3p in hFOB 1.19 cell accompanied by increased proliferating cell nuclear antigen (PCNA) and Ki67 expression, whereas miR-187-3p knockdown led to an inhibition of cell proliferation. Moreover, our data revealed that miR-187-3p was decreased in hFOB 1.19 cells undergoing osteoblastic differentiation. Silencing of miR-187-3p dramatically accelerated hFOB 1.19 osteoblastic differentiation, as evidenced by the increase of alkaline phosphatase (ALP) activity and calcium deposition, as well as elevated osteopontin (OPN), collagen type I alpha 1 (COL1A1), and bone sialoprotein (BSP) gene expression, whereas overexpression of miR-187-3p suppressed osteoblastic differentiation. Furthermore, we demonstrated that miR-187-3p could inhibit cannabinoid receptor type 2 (CNR2) expression by targeting its 3' untranslated region (UTR). Upregulation of CNR2 inversed the inhibiting influence of miR-187-3p on hFOB 1.19 osteogenic differentiation. Collectively, our results showed a pivotal role of miR-187-3p/CNR2 axis in osteoblastic differentiation, indicating that miR-187-3p may serve as a promising target in the therapy of osteoporosis.

Nrf2 deficiency aggravates the increase in osteoclastogenesis and bone loss induced by inorganic arsenic.

Arsenic exposure increases the risk of various bone disorders. For instance, chronic exposure to low level arsenic can cause bone resorption by promoting osteoclast differentiation. Osteoclast precursor cells produce hydrogen peroxide after low level arsenic exposure and then undergo differentiation, producing cells which break down bone matrix. Nuclear factor E2-related factor 2 (Nrf2) regulates receptor activator of nuclear factor-κB dependent osteoclastogenesis by modulating intracellular reactive oxygen species (ROS) signaling via expression of cytoprotective enzymes. Here we tested the hypothesis that loss of Nrf2 will increase arsenic-induced bone loss. We treated 40 week-old Nrf2+/+ and Nrf2-/- mice with 5 ppm arsenic in the drinking water, which produces a blood arsenic level similar to humans living in areas where arsenic exposure is endemic. After 4 months, Micro-CT and dual-energy x-ray analysis revealed a drastic overall decrease in the bone volume with arsenic treatment in mice lacking Nrf2. Deficiency of Nrf2 in RAW 264.7 cells or bone marrow-derived macrophages (BMMs) promoted arsenic-induced osteoclast differentiation. Lack of Nrf2 increases arsenic-induced ROS levels and phosphorylation of p38. N-Acetyl-cysteine and SB203580 pretreatment essentially abolished arsenic-induced phosphorylation of p38 and reversed arsenic-induced increased osteoclast differentiation in Nrf2 deficiency. Taken together, our data suggest that loss of Nrf2 causes increased oxidative stress and enhanced susceptibility to arsenic-induced bone loss.

An An Open-Label, Single Center, Retrospective Study to Evaluate Clinical Outcomes with Surgical Sealant in Bentall Procedures: A Cohort Study.

BACKGROUND: Cardiovascular surgery is associated with substantial risk for postoperative bleeding with increased patient morbidity and mortality. Numerous intraoperative techniques have been utilized to reduce this risk. This study was to assess postoperative bleeding-related parameters following Bentall procedures and to examine the impact of intraoperative surgical sealant application. METHOD: The medical/surgical records of 100 consecutive Bentall procedure cases were examined retrospectively for perioperative surgical sealant use and postoperative bleeding-related outcomes. RESULTS: Of the 100 patient cases, three died during the postoperative period, and 97 were evaluable. Surgical sealant was utilized in 56 patient cases (57.8%). The utilization versus no utilization of surgical sealant was associated with significant reductions in most postoperative bleeding-related parameters, including less drainage (P = .028), resternotomy for hemorrhage (P = .036), transfusion of red blood cells (P = .022 at 48 hours; P = .027 total in-hospital), transfusion of fresh frozen plasma (P = .04 at 48 hours; P = .004 total in-hospital), and a higher percentage of cases not needing blood transfusion (P = .002). The surgical sealant group had longer cardiopulmonary bypass circuit (P = .016) and aortic cross-clamp time (P = .001), with no significant between-group differences in intubation time (P = .636) or intensive care unit duration (P = .294). When excluding urgent cases or Stanford type A aortic dissections, intensive care unit duration significantly was shorter in the surgical sealant group (P = .017). Surgical sealant use was not associated with any adverse events. CONCLUSION: The application of surgical sealant to the anastomosis suture line in Bentall procedures reduces postoperative drainage, bleeding, and transfusion utilization. Further studies are warranted to investigate these benefits in prospective, randomized clinical trials.

Safety and Efficacy of Remote Ischemic Preconditioning in Patients With Severe Carotid Artery Stenosis Before Carotid Artery Stenting: A Proof-of-Concept, Randomized Controlled Trial.

BACKGROUND: Remote ischemic preconditioning (RIPC) can inhibit recurrent ischemic events effectively in patients with acute or chronic cerebral ischemia. However, it is still unclear whether RIPC can impede ischemic injury after carotid artery stenting (CAS) in patients with severe carotid artery stenosis. METHODS: Subjects with severe carotid artery stenosis were recruited in this randomized controlled study, and assigned to RIPC, sham, and no intervention (control) groups. All subjects received standard medical therapy. Subjects in the RIPC and sham groups underwent RIPC and sham RIPC twice daily, respectively, for 2 weeks before CAS. Plasma neuron-specific enolase and S-100B were used to evaluate safety, hypersensitive C-reactive protein, and new ischemic diffusion-weighted imaging lesions were used to determine treatment efficacy. The primary outcomes were the presence of ≥1 newly ischemic brain lesions on diffusion-weighted imaging within 48 hours after stenting and clinical events within 6 months after stenting. RESULTS: We randomly assigned 189 subjects in this study (63 subjects in each group). Both RIPC and sham RIPC procedures were well tolerated and completed with high compliance (98.41% and 95.24%, respectively). Neither plasma neuron-specific enolase levels nor S-100B levels changed significantly before and after treatment. No severe adverse event was attributed to RIPC and sham RIPC procedures. The incidence of new diffusion-weighted imaging lesions in the RIPC group (15.87%) was significantly lower than in the sham group (36.51%; relative risk, 0.44; 96% confidence interval, 0.20-0.91; P<0.01) and the control group (41.27%; relative risk, 0.39; 96% confidence interval, 0.21-0.82; P<0.01). The volumes of lesions were smaller in the RIPC group than in the control and sham groups (P<0.01 each). Ischemic events that occurred after CAS were 1 transient ischemic attack in the RIPC group, 2 strokes in the control group, and 2 strokes and 1 transient ischemic attack in the sham group, but these results were not significantly different among the 3 groups (P=0.597). CONCLUSIONS: RIPC is safe in patients undergoing CAS, which may be able to decrease ischemic brain injury secondary to CAS. However, the mechanisms and effects of RIPC on clinical outcomes in this cohort of patients need further investigation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01654666.

The Role of Alpha-Lipoic Acid in the Pathomechanism of Acute Ischemic Stroke.

BACKGROUND/AIMS: Ischemic stroke results in increased cerebral infarction, neurological deficits and neuroinflammation. The underlying mechanisms involving the anti-inflammatory and neuroprotective properties of α-Lipoic acid (α-LA) remain poorly understood. Herein, we investigated the potential role of α-LA in a middle cerebral artery occlusion (MCAO) rat model and an in vitro lipopolysaccharide (LPS)-induced microglia inflammation model. METHODS: In the in vivo study, infarct volume was examined by TTC staining and Garcia score was used to evaluate neurologic recovery. The cytokines were evaluated by enzyme-linked immunosorbent assay, and protein expression of microglia phenotype and NF-κB were measured using western blot. In the in vitro study, the expressions of microglia M1/M2 phenotype were evaluated using qRT-PCR, and immunofluorescence staining was used to assess the nuclear translocation of NF-κB. RESULTS: Both 20 mg/kg and 40 mg/kg of α-LA alleviated infarct size, brain edema, and neurological deficits. Furthermore, α-LA induced the polarization of microglia to the M2 phenotype, modulated the expression of IL-1ß, IL-6, TNF-α and IL-10, and attenuated the activation of NF-κB after MCAO. α-LA inhibited the expression of M1 markers, increased activation of the M2 markers, and suppressed the nuclear translocation of NF-κB in LPS-stimulated BV2 microglia. CONCLUSIONS: α-LA improved neurological outcome in experimental stroke via modulating microglia M1/M2 polarization. The potential mechanism of α-LA might be mediated by inhibition of NF-κB activation via regulating phosphorylation and nuclear translocation of p65.

Immune-related proteins detected through iTRAQ-based proteomics analysis of intestines from Apostichopus japonicus in response to tussah immunoreactive substances.

Apostichopus japonicus is a species of sea cucumber that is extensively bred as a marine delicacy because of its high nutritive and medicinal value. Immunostimulants are usually used to enhance the immunity of sea cucumber against diseases, but the physiological function of immunostimulants is poorly understood. In this study, we fed A. japonicus individuals with a diet supplemented with different concentrations of tussah immunoreactive substances (TIS), and then subjected their intestines to iTRAQ-based proteomic analysis. A total of 51 differentially expressed proteins were detected in response to TIS, 13 proteins were upregulated, while 38 proteins were reduced. These proteins are involved in phagocytosis, tissue protection, cell apoptosis and energy metabolism. Among these 51 proteins, 7 proteins (GLO2, ACOX, CTTN, MARK, FADD, CSTA and CASP6) related to immunity with functional annotation in sea cucumber were further analyzed. In addition, the upregulated expression of 4 immune-related proteins (GLO2, ACOX, CTTN and MARK) was validated by qRT-PCR. The findings of this study gave further insight into the mechanism by which TIS might enhance the immunity of A. japonicus.

Association between dietary patterns and hypertension among Han and multi-ethnic population in southwest China.

BACKGROUND: Different dietary patterns and the risks of hypertension in various diet exposures among multi-ethnic population in southwest China remain extremely scarce. The aim of this study is to identify dietary patterns and explore the association between dietary patterns and the risk of hypertension among Han and multi-ethnic population in southwest China. METHODS: A representative sample of 3591 participants of Han, and multi-ethnic population were recruited by stratified cluster sampling in Diqing of Yunnan Province, southwest China from September 2012 to January 2013. Participants who were under 18 years old or who could not clearly answer the questions and those who used the anti-hypertensive medication were excluded from this survey. All participants reported their dietary intakes using validated food frequency questionnaires (FFQ), and their blood pressures were measured by standardized procedures. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg. Dietary patterns were identified by factor analysis with principal component. Logistic regression was used to explore the association between dietary patterns and hypertension. RESULTS: The overall prevalence of hypertension was 30.5% among Han and multi-ethnic population in Diqing, Yunnan Province. Three dietary patterns were identified in this study, defined as 'Grassland healthy', 'Tuber and meat', and 'Fruit and vegetable'. Participants in the 5th quintile of the three dietary patterns were at a lower risk of hypertension compared with those in the 1st quintile. The odds ratio (OR) for the 5th quintile of 'Grassland healthy' pattern, 'Tuber and meat' and 'Fruit and vegetable' was 0.693 (95% CI: 0.537-0.893, p = 0.005), 0.678 (95% CI: 0.530-0.868, p = 0.002), 0.759 (95% CI: 0.593-0.970, p = 0.028), respectively. After further adjustment of participants' age, the negative association between the 'Grassland healthy' pattern and the prevalence of hypertension persisted (OR = 0.703, 95% CI: 0.535-0.924, p = 0.012). However, the significant associations between the other two dietary patterns and hypertension disappeared. CONCLUSIONS: The 'Grassland healthy' dietary pattern is associated with lower risk of hypertension, whereas there is no significant associations between the other two dietary patterns and hypertension among Han and multi-ethnic population in Diqing of Yunnan province, southwest China.

α-Lipoic Acid Promotes Neurological Recovery After Ischemic Stroke by Activating the Nrf2/HO-1 Pathway to Attenuate Oxidative Damage.

BACKGROUND/AIMS: Alpha-lipoic acid (α-LA) has been demonstrated to be protective against cerebral ischemia injury. Herein, we investigate the neuroprotective effect and underlying mechanisms of α-LA. METHODS: In vivo study, α-LA was administered intravenously upon reperfusion of transient middle cerebral artery occlusion. Garcia score was used to evaluate neurologic recovery. Infarct volume was examined by TTC staining, and oxidative damage was evaluated by ELISA assay. In an in vitro study, neurons were pretreated with α-LA at different doses and then subjected to OGD. Lentiviral vectors were applied to knockdown nuclear factor-erythroid 2-related factor-2 (Nrf2) or heme oxygenase-1 (HO-1). Cell viability was measured using CCK8. Protein expression was evaluated using western blot, and immunofluorescence staining was assessed. RESULTS: α-LA significantly reduced the infarct volume, brain edema, and oxidative damage and promoted neurologic recovery in rats. Pretreatment of α-LA caused an obvious increase in cell viability and a decrease in intracellular reactive oxygen species. Western blot analyses and immunofluorescence staining demonstrated a distinct increase in Nrf2 and HO-1 protein expression. Conversely, knockdown of Nrf2 or HO-1 resulted in the down-regulation of HO-1 protein and inhibited the neuroprotective effect of α-LA. CONCLUSION: α-LA treatment is neuroprotective and promotes functional recovery after ischemic stroke by attenuating oxidative damage, which is partially mediated by the Nrf2/HO-1 pathway.

Synbiotic dietary supplement affects growth, immune responses and intestinal microbiota of Apostichopus japonicus.

A feeding experiment was conducted to investigate the effects of dietary administration of synbiotic with Bacillus lincheniformis WS-2 (CGMCC No. 12813) and alginate oligosaccharides (AOS) on the growth, innate immune response, and intestinal microbiota of the sea cucumber Apostichopus japonicus and its resistance to Vibrio infection. Sea cucumbers were given a control diet (non-supplemented), pro diet (basal diet plus 1 × 109 cfu (g diet)-1B. lincheniformis WS-2), syn diet (basal diet plus 1 × 109 cfu (g diet)-1B. lincheniformis WS-2 and 10 g (kg diet) -1 AOS) or pre diet (basal diet plus 10 g (kg diet) -1 AOS) over a period of 60 days, and the growth performance and various innate immune parameters of the animals were evaluated after 30 and 60 days of feeding. No significant difference in growth performance was observed between the group fed with the syn and the group fed with the pro diet, but both these groups exhibited significant (P < 0.05) enhancement in growth performance compared to the control group. At the same time, both syn and pro diets also resulted in the animals having significantly higher levels of amylase, protease and alginate lyase activities compared to the con diet. Individuals fed with the syn or pro diet showed enhanced levels of various immune enzyme activities, compared to those fed with the con diet. At the end of the growth period, the sea cucumbers were challenged with Vibrio splendidus via intraperitoneal injection. The survival rates of sea cucumbers fed with the syn, pro or pre diet were significantly improved compared to that of sea cucumbers fed with the con diet, with sea cucumbers fed with synbiotic having the highest survival. In addition, increased proportions of Bacillus and Lactococcus were found in the intestinal tract of sea cucumbers fed with the syn diet (9.5% and 7.3%) compared to those of sea cucumbers fed with the pro diet (6.1% and 4.6%), con diet (4.0% and 3.4%), or pre diet (5.2% and 6.8%) after 60 days of feeding. Furthermore, the proportion of Vibrio in the intestinal tracts of sea cucumbers fed with the pro diet (2%) or syn diet (3.1%) was lower than that of sea cucumbers fed with the con diet (5.5%) or pre diet (3.8%), although no significant difference was detected between the pro diet and syn diet groups (P > 0.05). Overall, the results suggested that dietary synbiotic consisting of Bacillus lincheniformis and alginate oligosaccharides (AOS) could have positive benefit for sea cucumber aquaculture.