Longitudinal Analysis of Overlapping Psychosocial Factors Predicting Incident Hospitalization Among Mixed HIV Serostatus Men who have Sex with Men in the Multicenter AIDS Cohort Study.

Men who have sex with men (MSM) are at increased risk for certain types of chronic diseases and mental health problems. Despite having extended survival in the highly active antiretroviral therapy (HAART) era, MSM living with HIV contend with aging-related diseases and complications with treatment. Consequent hospitalizations incur high costs, fear, low quality of life, and frailty. Unlike heterosexual men, MSM experience more structural violence and "syndemics" of psychosocial factors that not only accelerate HIV acquisition and transmission risk but also may increase morbidity, leading to greater rates of hospitalization. We aim to examine the impact of "syndemic" psychosocial factors on the incidence of hospitalization among geographically diverse MSM in the US. Participants were 1760 MSM from the Multicenter AIDS Cohort Study (MACS) between 2004 and 2019. We examined the relationship between six psychosocial factors (depression, stimulant use, smoking, heroin use, childhood sexual abuse, and intimate partner violence) and incident hospitalization (admission to a hospital for treatment). We found a positive dose-response relationship between the number of syndemic factors and hospitalization. MSM reporting five or more syndemic factors had over twice the risk of hospitalization compared to MSM without syndemic factors [aRR = 2.14 (95% CI = 1.56, 2.94)]. Psychosocial factors synergistically increased hospitalizations over time. The positive dose-response relationship between the number of syndemic factors and hospitalization and the synergistic effects of these factors underscore the need for interventions that disentangle the syndemics to reduce hospitalization and related costs and improve the quality of life among MSM.

Modified robot-assisted nephroureterectomy with ureteral catheterization for radical resection of the distal ureter: Procedures and short-term outcomes.

Objectives: To describe a bladder cuff excision method modified with ureteral catheterization to better visualize the ureteral orifice during robot-assisted nephroureterectomy (RANU). Methods: We retrospectively analyzed 66 patients with upper urinary tract urothelial carcinoma of the renal pelvis and/or upper-mid ureter treated between January 2020 and January 2023. Among them, 32 patients (group A) underwent RANU supported by ureteral catheterization, and the remaining patients (group B) received routine transperitoneal RANU. Postoperative cystoscopy was performed routinely to compare the rates of residual ureteral orifice between the two groups. Results: Surgeries were completed uneventfully in all 66 patients, without blood transfusion or conversion to open procedures. The operative time, estimated blood loss, and postoperative length of hospital stay were similar between both groups. However, the mean time required for BCE in group A was shorter than that in group B (9.5 min vs. 16.0 min, p = 0.006). Cystoscopy at postoperative three months showed no ipsilateral ureteral orifice in group A, but residual ureteral orifice was found in 23.5% of patients in group B. During a short follow-up period of 16 months, no patients in group A experienced bladder tumor recurrence. However, two patients (5.9%) in group B developed bladder tumor recurrence, with one experiencing local tumor recurrence at the level of the ureteral stump. Conclusions: Our novel technique enables complete ureteral retrieval, accurate and rapid bladder cuff excision, which makes the procedure less invasive and safely reproducible during robot-assisted nephroureterectomy.

CRISPR genome-wide screening identifies PAK1 as a critical driver of ARSI cross-resistance in prostate cancer progression.

Next-generation androgen receptor signaling inhibitors (ARSIs), such as enzalutamide (Enza) and darolutamide (Daro), are initially effective for the treatment of advanced prostate cancer (PCa) and castration-resistant prostate cancer (CRPC). However, patients often relapse and develop cross-resistance, which consequently makes drug resistance an inevitable cause of CRPC-related mortality. By conducting a comprehensive analysis of GEO datasets, CRISPR genome-wide screening results, ATAC-seq data, and RNA-seq data, we systemically identified PAK1 as a significant contributor to ARSI cross-resistance due to the activation of the PAK1/RELA/hnRNPA1/AR-V7 axis. Inhibition of PAK1 followed by suppression of NF-κB pathways and AR-V7 expression effectively overcomes ARSI cross-resistance. Our findings indicate that PAK1 represents a promising therapeutic target gene for the treatment of ARSI cross-resistant PCa patients in the clinic. STATEMENT OF SIGNIFICANCE: PAK1 drives ARSI cross-resistance in prostate cancer progression.

Incidence of Adjacent Segment Degeneration and Its Associated Risk Factors Following Anterior Cervical Discectomy and Fusion: A Meta-Analysis.

OBJECTIVE: This study aimed to investigate the incidence of adjacent segment degeneration (ASD) and its associated risk factors in adults after anterior cervical discectomy and fusion (ACDF) surgery. METHODS: An exhaustive search across multiple databases was conducted, including Embase, PubMed, Cochrane Library, and the Web of Science, to identify pertinent studies. We collected such patient data as demographic variables (including age, gender, body mass index), cervical spondylosis type (such as radiculopathy and myelopathy), diabetes status, smoking and drinking history, and radiological risk factors (such as preoperative ASD status, developmental spinal stenosis, T1 slope, and postoperative less cervical lordosis). Incidence estimates were calculated based on relevant data. Risk factors were assessed using odds ratios and weighted mean differences with 95% confidence intervals (CIs). RESULTS: Our analysis incorporated a total of 21 studies for incidence analysis. The overall incidence of CASD following ACDF was found to be 11% and radiographical ASD was 30%. Old age (weighted mean difference = 3.21; 95% CI: 0.06, 6.36; P = 0.05), preoperative ASD status (odds ratio = 2.65; 95% CI: 1.53, 4.60; P < 0.01), developmental spinal stenosis (odds ratio = 2.46; 95% CI: 1.61, 3.77; P < 0.01), and postoperative reduction in cervical lordosis were identified as significant risk factors for the occurrence of CASD. CONCLUSIONS: The incidence of CASD following ACDF was 11%. Risk factors for CASD included old age, preoperative adjacent segment degeneration, developmental spinal stenosis, and postoperative reduction in cervical lordosis. These findings provide valuable insights for the assessment of adjacent segment disease risk after ACDF, aiding surgeons in diagnosis and treatment decisions.

Evaluating the Role of Morphological Parameters in the Prostate Transition Zone in PHI-Based Predictive Models for Detecting Gray Zone Prostate Cancer.

Background: The early detection of clinically significant prostate cancer (csPCa) through the integration of multidimensional parameters presents a promising avenue for improving survival outcomes for this fatal disease. This study aimed to assess the contribution of prostate transition zone (TZ) to predictive models based on the prostate health index (PHI), with the goal of enhancing early detection of csPCa in the prostate-specific antigen (PSA) gray zone. Methods: In this observational cross-sectional study, a total of 177 PSA gray zone patients (total prostate-specific antigen [tPSA] level ranging from 4.0 to 10.0 ng/mL) were recruited and received PHI detections from August 2020 to March 2022. Prostatic morphologies especially the TZ morphological parameters were measured by transrectal ultrasound (TRUS). Results: Univariable logistic regression indicated prostatic morphological parameters including total prostate volume (PV) indexes and transitional zone volume indexes were all associated with csPCa (P < .05), while the multivariable analysis demonstrated that C-reactive protein (CRP), PHI, PHI density (PHID), and PHI transition zone density (PHI-TZD) were the 4 independent risk factors. The receiver-operating characteristic (ROC) curve analysis suggested that integrated predictive models (PHID, PHI-TZD) yield area under the curves (AUCs) of 0.9135 and 0.9105 in csPCa prediction, which shows a relatively satisfactory predictive capability compared with other predictors. Moreover, the PHI-TZD outperformed PHID by avoiding 30 patients' unnecessary biopsies while maintaining 74.36% specificity at a sensitivity of 90%. Decision-curve analysis (DCA) confirmed the comparable performance of the multivariable full-risk prediction models, without the inclusion of the net benefit, thereby highlighting the superior diagnostic efficacy of PHID and PHI-TZD in comparison with other diagnostic models, in both univariable and multivariable models. Conclusion: Our data confirmed the value of prostate TZ morphological parameters and suggested a significant advantage for the TZ-adjusted PHI predictive model (PHI-TZD) compared with PHI and PHID in the early detection of gray zone csPCa under specific conditions.

Angle-dependent broadband asymmetric acoustic transmission in a planar device.

Asymmetric manipulation of acoustic transmission is of fundamental interest for wave physics, and has attracted rapidly-growing attentions owing to the potential applications in diverse scenarios. Here we propose to realize angle-dependent asymmetric acoustic transmission by designing a planar structure comprising a gradient-index layer and a layer of homogeneous medium with relatively-lower index. We analytically derive the working frequency and angle range of the device with unidirectional mechanism. And the simulated results show that the proposed device gives rise to high-efficiency broadband asymmetric transmission by allowing acoustic waves normally incident on one side to pass, while behaving as an acoustic barrier blocking waves obliquely incoming from both directions as angle of incidence exceeds a critical angle. Bearing the advantages of simple design, broad bandwidth and switchable functionality, our scheme opens a route to the design of novel acoustic devices capable of adapting various circumstances, and may find applications in noise control, medical detection, etc.

Changes of Short-Term Heart Rate Variability and Vertebral Artery Magnetic Resonance Angiography in Patients with Cervical Vertigo.

Cervical vertigo refers to a clinical syndrome with sudden vertigo as the main symptom caused by the hemodynamic disturbance of the extracranial segment of the vertebral artery (VA) affected by cervical vertebral lesions. Small differences in pulse intervals in a patient's continuous sinus rhythm are called heart rate variability (HRV). Heart rate variability refers to the small rise and fall of instantaneous heart rate between consecutive beats and is one of the most important physiological indicators of cardiac function. Small changes between successive beats reflect some information about the heart. So, it can be used to diagnose heart disease; its parameters can be used to identify emotions. Therefore, it is possible to use the characteristics of heart rate variability to find some patterns in the high-stress state and use the computer and ECG signals to describe the high-stress state. Since the ECG signal is a universal and objective model, it is practical and convenient to use it to describe stress states. Magnetic resonance angiography (MR angiography, MRA) is a noninvasive vascular imaging method that does not require intubation and contrast agents. At present, it has been widely used in clinical practice. In order to explore the changes of short-term heart rate variability and vertebral arterial magnetic resonance angiography (MRA) in patients with cervical vertigo and their clinical significance, this paper introduces two basic analysis methods of heart rate variability and commonly used MRA techniques, TOF technology. In the analysis of heart rate variability in patients with cervical vertigo, the statistical values of time and spectrum domain parameters were found to be lower in the experimental group than in the control group1. MRA showed that the abnormal rate of VA in the PCI group and the cervical vertigo group was similar. In the RMSSD index, the male experimental group reached 29, and the control group 1 reached 22.

Serum multi-cytokines screening identifies TRAIL and IL-10 as probable new biomarkers for prostate health index diagnostic utility adjustment in grey zone aggressive prostate cancer detection: A single-center data in China.

Objective: To identify less invasive and easily applicable serum cytokine-derived biomarkers which contribute to the diagnostic utility and risk assessment ability of the prostate health index (PHI) based multivariable model in grey zone aggressive prostate cancer (AG PCa) early detection. Methods: Serum 45 cytokines screening was performed in a small training cohort consisting of 10 sera by Luminex liquid array-based multiplexed immunoassays and identified TRAIL and IL-10 as new biomarkers for PHI diagnostic utility adjustment for further validation with a multivariable predictive model in a cohort including 79 aggressive prostate cancer patients and 209 benign prostatic hyperplasia or indolent PCa patients within the PSA grey zone. Results: TRAIL and IL-10 were identified as potential serum biomarkers for AG PCa detection by the result of multi-cytokines screening in the univariate analysis, while multivariable logistic regression confirmed the AUC of the full risk predictive model (0.915) including tPSA, fPSA, PHI, TRAIL, and IL-10 was higher than various diagnostic strategies. DCA suggested a superior net benefit and indicated a good discriminative ability of the full risk model consistently with the result of the nomogram. Conclusion: We suggest a significant advantage for the PHI-based multivariate combinations of serum TRAIL and IL-10 comparing to PHI or other serum-derived biomarkers alone in the detection and risk stratification of grey zone AG PCa.

Fluorescent Covalent Organic Frameworks: A Promising Material Platform for Explosive Sensing.

Covalent organic frameworks (COFs) are a novel class of porous crystalline organic materials with organic small molecule units connected by strong covalent bonds and extending in two- or three-dimension in an ordered mode. The tunability, porosity, and crystallinity have endowed covalent organic frameworks the capability of multi-faceted functionality. Introduction of fluorophores into their backbones or side-chains creates emissive covalent organic frameworks. Compared with common fluorescent organic solid materials, COFs possess several intrinsic advantages being as a type of irreplaceable fluorescence materials mainly because its highly developed pore structures can accommodate various types of guest analytes by specific or non-specific chemical bonding and non-bonding interaction. Developments in fluorescent COFs have provided opportunities to enhance sensing performance. Moreover, due to its inherent rigidified structures and fixed conformations, the intramolecular rotation, vibration, and motion occurred in common organic small molecules, and organic solid systems can be greatly inhibited. This inhibition decreases the decay of excited-state energy as heat and blocks the non-radiative quenching channel. Thus, fluorescent COFs can be designed, synthesized, and precisely tuned to exhibit optimal luminescence properties in comparison with common homogeneous dissolved organic small molecule dyes and can even compete with the currently mainstream organic solid semiconductor-based luminescence materials. This mini-review discusses the major design principle and the state-of-the-art paragon examples of fluorescent COFs and their typical applications in the detection and monitoring of some key explosive chemicals by fluorescence analysis. The challenges and the future direction of fluorescent COFs are also covered in detail in the concluding section.

Modified Prostate Health Index Density Significantly Improves Clinically Significant Prostate Cancer (csPCa) Detection.

Background: Early screening of clinically significant prostate cancer (csPCa) may offer opportunities in revolutionizing the survival benefits of this lethal disease. We sought to introduce a modified prostate health index density (mPHI) model using imaging indicators and to compare its diagnostic performance for early detection of occult onset csPCa within the prostate-specific antigen (PSA) gray zone with that of PHI and PHID. Methods and Participation: Between August 2020 and January 2022, a training cohort of 278 patients (total PSA 4.0-10.0 ng/ml) who were scheduled for a prostate biopsy were prospectively recruited. PHI and PHID were compared with mPHI ( LD TRD × APD × TPV × PHI ) for the diagnosis performance in identifying csPCa. Pathology outcomes from systematic prostate biopsies were considered the gold standard. Results: This model was tested in a training cohort consisting of 73 csPCa, 14 non-clinically significant prostate cancer(non-csPCa), and 191 benign prostatic hyperplasia (BPH) samples. In the univariate analysis for the PSA gray zone cohort, for overall PCa, the AUC of mPHI (0.856) was higher than PHI (0.774) and PHID (0.835). For csPCa, the AUC of mPHI (0.859) also surpassed PHI (0.787) and PHID (0.825). For detection of csPCa, compared with lower specificities from PHI and PHID, mPHI performed the highest specificity (76.5%), by sparing 60.0% of unnecessary biopsies at the cost of missing 11 cases of csPCa. The mPHI outperformed PHI and PHID for overall PCa detection. In terms of csPCa, mPHI exceeds diagnostic performance with a better net benefit in decision curve analysis (DCA) compared with PHI or PHID. Conclusions: We have developed a modified PHI density (mPHI) model that can sensitively distinguish early-stage csPCa patients within the PSA gray zone. Clinical Trial Registration: ClinicalTrials.gov, NCT04251546.

The modified prostate health index (PHI) outperforms PHI density in the detection of clinical prostate cancer within the PSA grey zone.

OBJECTIVES: To compare the accuracy of several volume and diameters modified prostate health index (mPHI) models with PHI density (PHID), PHI, and other prostate-specific antigen (PSA) derivatives in detecting PSA grey zone prostate cancer (PCa). MATERIALS AND METHODS: Between August 2020 and September 2021, a consecutive cohort of 214 suspected PCa patients with elevated total PSA values ranged from 4.0 to 10.0 ng/mL were prospectively recruited and received PHI detections and transrectal ultrasonography (TRUS) measurements, followed by systematic prostate biopsies confirmation. RESULTS: Among the 214 patients enrolled in the project, a total of 80 were diagnosed with PCa. In univariate analysis for the training cohort, the area under curve (AUC) of mPHI-2 [Formula: see text] was 0.8310, which outperformed PHID in identifying PSA grey zone PCa (P ≤ 0.0001) and showed the best net benefit in decision curve analysis (DCA). By a threshold of 0.2835, the sensitivity and specificity in the prediction of PCa were 78.9% and 90.3%, while the positive predictive value (PPV) and negative predictive value (NPV) were 78.3% and 78.6%, respectively. CONCLUSIONS: According to our present single-center experience, the mPHI-2 risk predictor outperformed PHID or other classical parameters alone in the PCa detection with a grey zone PSA level in Asian males.

Association of the VACS Index With Hospitalization Among People With HIV in the NA-ACCORD.

BACKGROUND: People with HIV (PWH) have a higher hospitalization rate than the general population. The Veterans Aging Cohort Study (VACS) Index at study entry well predicts hospitalization in PWH, but it is unknown if the time-updated parameter improves hospitalization prediction. We assessed the association of parameterizations of the VACS Index 2.0 with the 5-year risk of hospitalization. SETTING: PWH ≥30 years old with at least 12 months of antiretroviral therapy (ART) use and contributing hospitalization data from 2000 to 2016 in North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) were included. Three parameterizations of the VACS Index 2.0 were assessed and categorized by quartile: (1) "baseline" measurement at study entry; (2) time-updated measurements; and (3) cumulative scores calculated using the trapezoidal rule. METHODS: Discrete-time proportional hazard models estimated the crude and adjusted associations (and 95% confidence intervals [CIs]) of the VACS Index parameterizations and all-cause hospitalizations. The Akaike information criterion (AIC) assessed the model fit with each of the VACS Index parameters. RESULTS: Among 7289 patients, 1537 were hospitalized. Time-updated VACS Index fitted hospitalization best with a more distinct dose-response relationship [score <43: reference; score 43-55: aHR = 1.93 (95% CI: 1.66 to 2.23); score 55-68: aHR = 3.63 (95% CI: 3.12 to 4.23); score ≥68: aHR = 9.98 (95% CI: 8.52 to 11.69)] than study entry and cumulative VACS Index after adjusting for known risk factors. CONCLUSIONS: Time-updated VACS Index 2.0 had the strongest association with hospitalization and best fit to the data. Health care providers should consider using it when assessing hospitalization risk among PWH.

Metal-Organic Frameworks With Variable Valence Metal-Photoactive Components: Emerging Platform for Volatile Organic Compounds Photocatalytic Degradation.

With their outstanding diversities in both structures and performances, newly emerging metal-organic frameworks (MOFs) materials are considered to be the most promising artificial catalysts to meet multiple challenges in the fields of energy and environment. Especially in absorption and conversion of solar energy, a variety of MOFs can be readily designed to cover and harvest the sun irradiation of ultraviolet (UV), visible and near-infrared region through tuning both organic linkers and metal nodes to create optimal photocatalytic efficiency. Nowadays, a variety of MOFs were successfully synthesized as powerful photocatalysts for important redox reactions such as water-splitting, CO2 reduction and aqueous environmental pollutants detoxification. MOFs applications in indoor-air VOCs pollutants cleaning, however, are less concerned partially because of limited diffusion of both gaseous pollutant molecules and photo-induced active species in very porous MOFs structures. In this mini-review, we focus on the major breakthroughs of MOFs as photocatalysts for the effective removal of indoor-air VOCs such as aldehydes, aromatics and short-chain alcohols. According to their nature of photoactive centers, herein MOFs photocatalysts are divided into two categories to comment, that is, MOFs with variable valence metal nodes as direct photoactive centers and MOFs with non-variable valence metal nodes but after combining other photoactive variable valence metal centers as excellent concentrated and concerted electron-transfer materials. The mechanisms and current challenges of the photocatalytic degradation of indoor-air VOC pollutants by these MOFs will be discussed as deeply as possible.

Covalent Organic Frameworks: New Materials Platform for Photocatalytic Degradation of Aqueous Pollutants.

Covalent organic frameworks (COFs) are highly porous and crystalline polymeric materials, constructed by covalent bonds and extending in two or threedimensions. After the discovery of the first COF materials in 2005 by Yaghi et al., COFs have experienced exciting progress and exhibitedtheirpromising potential applications invarious fields, such as gas adsorption and separation, energy storage, optoelectronics, sensing and catalysis. Because of their tunablestructures, abundant, regular and customizable pores in addition to large specific surface area, COFs can harvest ultraviolet, visible and near-infrared photons, adsorb a large amount of substrates in internal structures and initiate surface redox reactions to act as effective organic photocatalysts for water splitting, CO2 reduction, organic transformations and pollutant degradation. In this review, we will discuss COF photocatalysts for the degradation of aqueous pollutants. The state-of-the-art paragon examples in this research area will be discussed according to the different structural type of COF photocatalysts. The degradation mechanism will be emphasized. Furthermore, the future development direction, challenges required to be overcome and the perspective in this field will be summarized in the conclusion.

Correction: A powerful azomethine ylide route mediated by TiO2 photocatalysis for the preparation of polysubstituted imidazolidines.

Correction for 'A powerful azomethine ylide route mediated by TiO2 photocatalysis for the preparation of polysubstituted imidazolidines' by Anan Liu et al., Org. Biomol. Chem., 2021, 19, 2192-2197, DOI: .

A powerful azomethine ylide route mediated by TiO2 photocatalysis for the preparation of polysubstituted imidazolidines.

Lewis- and Brønsted-acid catalyzed 1,3-dipolar cycloaddition between azomethine ylides and unsaturated compounds is an important strategy to construct five-membered N-heterocycles. However, such a catalytic route usually demands substrates with an electron-withdrawing group (EWG) to facilitate the reactivity. Herein, we report a TiO2 photocatalysis strategy that can conveniently prepare five-membered N-heterocyclic imidazolidines from a common imine (N-benzylidenebenzylamine) and alcohols along the route of 1,3-dipolaron azomethine ylide but without pre-installed EWG substituents on the substrates. Our EPR results uncovered the previously unknown mutual interdependence between an azomethine ylide and TiO2 photo-induced hvb+/ecb- pair. This transformation exhibited a broad scope with 21 successful examples and could be scaled up to the gram level.

Age and Sex Disparities in Sexual Trauma, Depressive Symptoms, and Antiretroviral Adherence Among People Living with HIV in the Deep South: A Mediation Analysis.

People living with HIV (PLWH) have a higher risk of experiencing sexual assault compared to populations without HIV. Prior studies have shown independent associations between sexual assault, depression, and antiretroviral therapy (ART) adherence. However, research analyzing the potential mediating effects of depressive symptoms between sexual assault and ART adherence, and the associated age and sex disparities, especially among PLWH in the Southern United States, is lacking. Therefore, the current study sought to determine whether depressive symptoms mediate the association between sexual assault and ART adherence and to evaluate the associated age and sex disparities among PLWH in South Carolina. Data were collected from 337 individuals who received HIV care from an immunology center in South Carolina. Crude and adjusted path analysis models stratified by age and sex were used to determine the association between sexual assault, depressive symptoms, and ART adherence. Depressive symptoms were associated with ART adherence among adults aged 18-34 (ß = - 0.281, p = .018) and 35-49 (ß = - 0.185, p = .005), and men (ß = - 0.205, p = .011). Sexual assault was associated with depressive symptoms (ß = 0.211, p = .001) and with ART adherence (ß = - 0.172, p = .010) among adults 35-49. Among men (ß = - 0.238; p = .029) and women (ß = - 0.344, p = .001), sexual assault was associated with ART adherence; among women, sexual assault was associated with depressive symptoms (ß = 0.280, p = .006). Depressive symptoms mediated the association between sexual assault and ART adherence among adults 35-49 (ß = - 0.039, p = .035). Interventions addressing depressive symptoms may improve ART adherence among adults aged 18-34 and 35-49 and men. Programs also addressing depressive symptoms and using trauma-informed approaches may improve ART adherence, especially among middle-age populations, men, and women.

The Effect of Pyrroloquinoline Quinone on the Expression of WISP1 in Traumatic Brain Injury.

WISP1, as a member of the CCN4 protein family, has cell protective effects of promoting cell proliferation and inhibiting cell apoptosis. Although some studies have confirmed that WISP1 is concerned with colon cancer and lung cancer, there is little report about the influence of WISP1 in traumatic brain injury. Here, we found that the expression of WISP1 mRNA and protein decreased at 3 d and then increased at 5 d after traumatic brain injury (TBI). Meanwhile, immunofluorescence demonstrated that there was little colocation of WISP1 with GFAP, Iba1, and WISP1 colocalized with NeuN partly. WISP1 colocalized with LC3, but there was little of colocation about WISP1 with cleaved caspase-3. Subsequent study displayed that the expression of ß-catenin protein was identical to that of WISP1 after TBI. WISP1 was mainly located in cytoplasm of PC12 or SHSY5Y cells. Compared with the negative control group, WISP1 expression reduced obviously in SHSY5Y cells transfected with WISP1 si-RNA. CCK-8 assay showed that pyrroloquinoline quinone (PQQ) had little influence on viability of PC12 and SHSY5Y cells. These results suggested that WISP1 played a protective role after traumatic brain injury in rats, and this effect might be relative to autophagy caused by traumatic brain injury.

The Effect of Pyrroloquinoline Quinone on Apoptosis and Autophagy in Traumatic Brain Injury.

BACKGROUND: Pyrroloquinoline quinone is an anionic, water-soluble compound with antioxidant characteristic. The role of pyrroloquinoline quinone in pharmacology and nutrition has attracted wide attention of researchers. Although a few experiments have confirmed that pyrroloquinoline quinone plays an obvious effective role in neuroprotection. There are few reports about the effect of pyrroloquinoline quinone on traumatic brain injury. Traumatic brain injury is one of the leading causes for adult disability and death. So far, there are no effective treatment methods for the injury because of its complex pathophysiology. METHOD: In the present study, a model of traumatic brain injury in rat was established to study the role of pyrroloquinoline quinone in central nervous system injury. RESULTS: The results showed that the protein expression of cleaved-Caspase 3/Caspase 3 increased after traumatic brain injury and the expression decreased by treatment with 2mM pyrroloquinoline quinone. Terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) staining displayed that the TUNEL positive signals were up-regulated after traumatic brain injury and were down-regulated after treatment with 2mM pyrroloquinoline quinone. The protein expression of LC3II/LC3I or lysosome-associated membrane protein 2(LAMP2) was elevated after traumatic brain injury and reduced after administration with 2mM pyrroloquinoline quinone. Transmission electron microscopy showed that the number of autophagosomes increased markedly after traumatic brain injury and decreased on administration of 2mM pyrroloquinoline quinone. Electroencephalogram indicated that pyrroloquinoline quinone improved brain electrophysiological function after traumatic brain injury. The results of CCK-8 test showed that pyrroloquinoline quinone could increase the viability of primary astrocyte treated with Glutamate. Lactate dehydrogenase (LDH) assay demonstrated that pyrroloquinoline quinone decreased LDH content in primary astrocyte exposed to Glutamate. CONCLUSION: Pyrroloquinoline quinone could play a neuroprotective role after traumatic brain injury in rat, which might be associated with inhibiting apoptosis and autophagy caused by traumatic brain injury.

Up-regulation of VCAM1 Relates to Neuronal Apoptosis After Intracerebral Hemorrhage in Adult Rats.

Vascular cell adhesion molecule 1 (VCAM1) is a member of the Immunoglobulin superfamily and encodes a cell surface sialoglycoprotein expressed in cytokine-activated endothelium. This type I membrane protein mediates leukocyte-endothelial cell adhesion, facilitates the downstream signaling, and may play a role in the development of artherosclerosis and rheumatoid arthritis. Accumulating evidence has demonstrated that VCAM1 exerts an anti-apoptotic effect in several tumor tissues such as ovarian cancer and breast cancer. Intracerebral hemorrhage (ICH) is the second most common subtype of stroke with high morbidity and mortality, which imposes a big burden on individuals and the whole society. These together prompted us to question whether VCAM1 has some association with neuron apoptosis during the pathological process of ICH. An ICH rat model was established and assessed by behavioral tests in order to explore the role of VCAM1 after ICH. Up-regulation of VCAM1 was observed in brain areas surrounding the hematoma following ICH by western blotting and immunohistochemistry. Immunofluorescence manifested VCAM1 was strikingly increased in neurons, but not in astrocytes and microglia. Furthermore, we detected that neuronal apoptosis marker active caspase-3 had co-localizations with VCAM1. At the same time, Bcl-2 was also co-localized with VCAM1. Taken together, our findings suggested that VCAM1 might be involved in the neuronal apoptosis and pathophysiology of ICH.