Classification and hemodynamic characteristics of delayed intracerebral hemorrhage following stent-assisted coil embolism in unruptured intracranial aneurysms.

Background and objective: Stent-assisted coil (SAC) embolization is a commonly used endovascular treatment for unruptured intracranial aneurysms (UIAs) but can be associated with symptomatic delayed intracerebral hemorrhage (DICH). Our study aimed to investigate the hemodynamic risk factors contributing to DICH following SAC embolization and to establish a classification for DICH predicated on hemodynamic profiles. Methods: This retrospective study included patients with UIAs located in the internal carotid artery (ICA) treated with SAC embolization at our institution from January 2021 to January 2022. We focused on eight patients who developed postoperative DICH and matched them with sixteen control patients without DICH. Using computational fluid dynamics, we evaluated the hemodynamic changes in distal arteries [terminal ICA, the anterior cerebral artery (ACA), and middle cerebral artery (MCA)] pre-and post-embolization. We distinguished DICH-related arteries from unrelated ones (ACA or MCA) and compared their hemodynamic alterations. An imbalance index, quantifying the differential in flow velocity changes between ACA and MCA post-embolization, was employed to gauge the flow distribution in distal arteries was used to assess distal arterial flow distribution. Results: We identified two types of DICH based on postoperative flow alterations. In type 1, there was a significant lower in the mean velocity increase rate of the DICH-related artery compared to the unrelated artery (-47.25 ± 3.88% vs. 42.85 ± 3.03%; p < 0.001), whereas, in type 2, there was a notable higher (110.58 ± 9.42% vs. 17.60 ± 4.69%; p < 0.001). Both DICH types demonstrated a higher imbalance index than the control group, suggesting an association between altered distal arterial blood flow distribution and DICH occurrence. Conclusion: DICH in SAC-treated UIAs can manifest as either a lower (type 1) or higher (type 2) in the rate of velocity in DICH-related arteries. An imbalance in distal arterial blood flow distribution appears to be a significant factor in DICH development.

Overlapping Stent Treatment for Ruptured Dissecting Aneurysms in Posterior Circulation.

Ruptured dissecting aneurysms in posterior intracranial circulation present significant clinical challenges and often cause poor prognoses. Our cohort used overlapping stents as the primary treatment. We analyzed the medical records of 27 patients (18 men/nine women) with ruptured posterior circulation dissecting aneurysms (PCDAs). Their average age was 52 years. We selected 11 patients who used Enterprise (EP) and LVIS stents overlappingly and matched them 1:1 with counterparts who received either EP or LVIS stents individually. Overlapping stents was a feasible treatment in all 27 cases. We successfully followed up 26 patients for ≥6 months. Regrettably, one patient died from intracranial hypertension on Day 7 post-procedure. Immediate post-procedure angiographies indicated Raymond grade I, II, and III occlusions of PCDAs in 16 (59.3%), 7 (25.9%), and 4 (14.8%) cases, respectively. At an average follow-up duration of 16.2 months, 25 patients (96.2%) had modified Rankin Scale scores of 0-2, signifying positive outcomes. One patient (3.8%) had a score of 3-4. Recurrence rates for the EP and LVIS stent groups were higher than those of the overlapping stent group (45.45% vs. 9.09%, p = 0.15 and 27.27% vs. 9.09%, p = 0.59, respectively). No significant difference in recurrence rates existed between the overlapping and single-stent groups. Similarly, follow-up outcomes were consistent between the two groups. Overlapping stents could be an efficient method for treating ruptured PCDAs.

Sacubitril/Valsartan Cannot Improve Cardiac Function Compared with Valsartan in Patients Suffering Nonvalvular Atrial Fibrillation without Systolic Heart Failure.

This study investigates the effect of sacubitril/valsartan (Sac/Val) in patients diagnosed with nonvalvular atrial fibrillation (AF) without systolic heart failure (SHF).Nonvalvular AF patients without SHF admitted to the People's Hospital of Bortala Mongol Autonomous Prefecture from December 2020 to December 2021 were enrolled and randomly divided into Sac/Val treatment group (group T) and valsartan treatment group (group C, control). For subgroup analysis, patients were divided into subgroups with and without diastolic heart failure (DHF). After 1-month adaptive phase and subsequent 3-month treatment period, patients were followed up in the cardiology clinic. Plasma levels of biochemical markers and echocardiographic parameters before and after treatment were evaluated, and DHF scores were computed to assess diastolic function.Of 61 enrolled patients, 46 patients completed follow-up. Sac/Val treatment did not increase the percentage of sinus rhythm. Although N-terminal pro-B-type natriuretic peptide (NT-proBNP) expression tended to be reduced in both groups after 3 months of treatment, the differences compared with respective baseline levels and between groups were not significant. According to subgroup analysis, although NT-proBNP expression in the subgroup with DHF was lower at follow-up compared to baseline, the difference was not statistically significant. Similarly, no marked differences in echocardiographic parameters or tissue Doppler parameters related to DHF were detected between the groups (P > 0.05). Additionally, a subgroup analysis found no significant variations in the echocardiographic measures (P > 0.05).Sac/Val is not superior to valsartan for the short-term treatment of patients suffering with AF without SHF in improving NT-proBNP level and cardiac function.

Agricultural waste biochar after potassium hydroxide activation: Its adsorbent evaluation and potential mechanism.

The agricultural waste (Goji branch) was pyrolyzed into biochars with one-step potassium hydroxide (KOH) activation under different processing conditions. The biochars were first characterized in structural features and functional groups and then evaluated for adsorptive performance with methylene blue as a model pollutant. Different adsorption models were applied to fit the adsorption process and reveal the possible mechanisms. The adsorption capacity was found to strongly correlate (R2 = 0.9642) with the surface area of the biochars, among which biochar K50%W29%C-700 (pyrolysis at 700 °C in the presence of 50 % KOH and 29 % water) possessed the largest surface area (1378 m2/g) and exhibited the highest adsorption capacity (769 mg/g) compared to its homologous products. Biochar K50%W29%C-700 also showed excellent recyclability and potent adsorption capacity toward other common organic pollutants. The results suggest that traces of water in agricultural wastes could significantly intensify the KOH-involved activation efficiency of producing porous biochar.

The role of blood podoplanin in patients with viral myocarditis.

Podoplanin (PDPN), a small mucin-like glycoprotein, was recently found to promote the generation of cardiac ectopic lymphoid follicles and anti-heart autoantibodies (AHA) in viral myocarditis (VMC) mice. Herein, we investigated the blood PDPN expression and its potential clinical value in VMC patients. Overall, 40 VMC patients were enrolled among 112 hospitalized patients with suspected myocarditis. Their serum PDPN levels were higher than those in controlled acute myocardial infarction (AMI) patients (n = 40) and healthy individuals (n = 30) (both p < 0.01) and positively correlated with CRP, IL-17, and IL-4 (all p < 0.01). Elevation of serum PDPN discriminated VMC from AMI (OR = 4.061, p < 0.01) and PDPN addition to the basic model (age, CRP, and peak cTNI) increased AUC values (from 0.822 to 0.933, p = 0.04). Additionally, the serum levels of PDPN ligand CCL-21 were also increased and correlated with PDPN (R = 0.59, p < 0.01) in VMC patients, accompanied by AHA production. Moreover, the anti-MHC antibody was closely related to PDPN levels (R = 0.53, p < 0.01), and anti-MHC-positive patients with VMC displayed higher percentages of CD4+IL-17A+PDPN+T cells and CD19+CCR7+B cells (both p < 0.05). Noticeably, VMC patients complicated by ventricular arrhythmias (27.50%) presented with AHA production and higher PDPN levels (p < 0.05). Finally, we screened out and verified that miR-182-5p directly targeted PDPN and negatively regulated its expression (all p < 0.01). These data suggested that blood PDPN might be a novel inflammation-associated biomarker for the early diagnosis of VMC and may contribute to AHA production by binding CCL-21 to recruit Th17 and B cells, which were regulated by miR-182-5p.

Microsurgical Treatment of Arteriovenous Malformations: A Single-Center Study Experience.

OBJECTIVE: The purpose of the study was to assess the functional outcomes after microsurgical resection of arteriovenous malformations (AVMs) and to compare the results between patients eligible for A Randomized Trial of Unruptured Brain Arteriovenous Malformations in this surgical series to the results reported and the ARUBA study. METHODS: We reviewed the records of 169 patients who underwent microsurgical treatment of arteriovenous malformation (AVMs) in our institution between January 2016 and December 2021. These patients' functional status was assessed using modified Rankin Scale (mRS) scores at the last follow-up and before treatment. The mRS scores at the latest follow-up were classified into good outcomes (mRS < 3) and poor outcomes (mRS ≥ 3). Clinical presentation, patients' demographics, AVM characteristics, follow-up time, and obliteration rate were analyzed. Subgroup analyses were performed on the whole cohort, comparing Spetzler-Martin Grade I and Grade II, and ARUBA-eligible AVMs. RESULTS: The initial hemorrhagic presentation occurred in 71 (42%) out of 169 patients. The majority of the patients presented with headaches (73%). The AVMs were completely obliterated in 166 (98.2%) patients. The series included 65 Spetzler-Martin Grade I (38.5%), 46 Grade II (27.2%), 32 Grade III (18.9%), 22 Grade IV (13%), and 4 Grade V (2.4%) AVMs. There were 98 unruptured and 79 ARUBA-eligible cases. Also, optimal functional outcome was achieved in 145 (85.8%) patients. The overall mortality rate was 5.3% (9/169). The multivariate analysis illustrated that a poor outcome was significantly associated with presurgical mRS ≥3 (p < 0.013; OR, 0.206; 95% CI 0.059-0.713), increasing age (p < 0.045; odds ratio [OR], 1.022; 95% CI 1.000-0.045), and female gender (p < 0.009; OR, 2.991; 95% CI 1.309-6.832). CONCLUSIONS: Our study suggests that better outcomes can be obtained using microsurgical resection in the majority of patients with AVMs. Independent predictors of poor outcomes after surgical resection of AVMs include increasing age at the time of surgery, poor presurgical functional status, and female gender. Supposing that patients are more suitable for microsurgery after presurgical examination, outcomes are normally better in that case than those achieved by multimodal interventions (such as conservative treatment or ARUBA treatment arm). Therefore, we recommend early surgical removal on all surgically accessible AVMs to prevent successive hemorrhages and the consequences of poor neurological outcomes.

Biosynthesis of diisooctyl 2,5-furandicarboxylate by Candida antarctica lipase B (CALB) immobilized on a macroporous epoxy resin.

Diisooctyl 2,5-furandicarboxylate (DEF), an ester derivative of 2,5-furandicarboxylic acid (FDCA, a bio-based platform chemical), resembles the physical and chemical properties of phthalates. Due to its excellent biodegradability, DEF is considered a safer alternative to the hazardous phthalate plasticizers. Although FDCA esters are currently mainly produced by chemical synthesis, the enzymatic synthesis of DEF is a green, promising alternative. The current study investigated the biosynthesis of DEF by Candida antarctica lipase B (CALB) immobilized on macroporous resins. Out of five macroporous resins (NKA-9, LX-1000EP, LX-1000HA, XAD-7HP, and XAD-8) evaluated, the LX-1000EP epoxy resin was identified as the best carrier for CALB, and the XAD-7HP weakly polar resin was identified as the second best. The optimal immobilization conditions were as follows: CALB (500 µL) and LX-1000EP (0.1 g) were incubated in phosphate butter (20 mM, pH 6.0) for 10 h at 35°C. The resulting immobilized CALB (EP-CALB) showed an activity of 639 U/g in the hydrolysis of p-nitrophenyl acetate, with an immobilization efficiency of 87.8% and an activity recovery rate of 56.4%. Using 0.02 g EP-CALB as the catalyst in 10 mL toluene, and the molar ratio of 2,5-dimethyl furanediformate (1 mmol/mL) and isooctyl alcohol (4 mmol/mL) that was 1:4, a DEF conversion rate of 91.3% was achieved after a 24-h incubation at 50°C. EP-CALB had similar thermal stability and organic solvent tolerance compared to Novozym 435, and both were superior to CALB immobilized on the XAD-7HP resin. EP-CALB also exhibited excellent operational stability, with a conversion rate of 52.6% after 10 repeated uses. EP-CALB could be a promising alternative to Novozym 435 in the biomanufacturing of green and safe plasticizers such as DEF.

Virtual simulation with AneuShape™ software for microcatheter shaping in intracranial aneurysm coiling: a validation study.

Background: The shaping of an accurate and stable microcatheter plays a vital role in the successful embolization of intracranial aneurysms. Our study aimed to investigate the application and the role of AneuShape™ software in microcatheter shaping for intracranial aneurysm embolization. Methods: From January 2021 to June 2022, 105 patients with single unruptured intracranial aneurysms were retrospectively analyzed with or without AneuShape™ software to assist in microcatheter shaping. The rates of microcatheter accessibility, accurate positioning, and stability for shaping were analyzed. During the operation, fluoroscopy duration, radiation dose, immediate postoperative angiography, and procedure-related complications were evaluated. Results: Compared to the manual group, aneurysm-coiling procedures involving the AneuShape™ software exhibited superior results. The use of the software resulted in a lower rate of reshaping microcatheters (21.82 vs. 44.00%, p = 0.015) and higher rates of accessibility (81.82 vs. 58.00%, p = 0.008), better positioning (85.45 vs. 64.00%, p = 0.011), and higher stability (83.64 vs. 62.00%, p = 0.012). The software group also required more coils for both small (<7 mm) and large (≥7 mm) aneurysms compared to the manual group (3.50 ± 0.19 vs. 2.78 ± 0.11, p = 0.008 and 8.22 ± 0.36 vs. 6.00 ± 1.00, p = 0.081, respectively). In addition, the software group achieved better complete or approximately complete aneurysm obliteration (87.27 vs. 66.00%, p = 0.010) and had a lower procedure-related complication rate (3.60 vs. 12.00%, p = 0.107). Without this software, the operation had a longer intervention duration (34.31 ± 6.51 vs. 23.87 ± 6.98 min, p < 0.001) and a higher radiation dose (750.50 ± 177.81 vs. 563.53 ± 195.46 mGy, p < 0.001). Conclusions: Software-based microcatheter shaping techniques can assist in the precise shaping of microcatheters, reduce operating time and radiation dose, improve embolization density, and facilitate more stable and efficient intracranial aneurysm embolization.

Six-month follow-up after recovery of COVID-19 Delta variant survivors via CT-based deep learning.

Purpose: Using computer-aided diagnosis (CAD) methods to analyze the discharge and 6-month follow-up data of COVID-19 Delta variant survivors, evaluate and summarize the recovery and prognosis, and improve people's awareness of this disease. Methods: This study collected clinical data, SGRQ questionnaire results, and lung CT scans (at both discharge and 6-month follow-up) from 41 COVID-19 Delta variant survivors. Two senior radiologists evaluated the CT scans before in-depth analysis. Deep lung parenchyma enhancing (DLPE) method was used to accurately segment conventional lesions and sub-visual lesions in CT images, and then quantitatively analyze lung injury and recovery. Patient recovery was also measured using the SGRQ questionnaire. The follow-up examination results from this study were combined with those of the original COVID-19 for further comparison. Results: The participants include 13 males (31.7%) and 28 females (68.3%), with an average age of 42.2 ± 17.7 years and an average BMI of 25.2 ± 4.4 kg/m2. Compared discharged CT and follow-up CT, 48.8% of survivors had pulmonary fibrosis, mainly including irregular lines (34.1%), punctuate calcification (12.2%) and nodules (12.2%). Compared with discharged CT, the ground-glass opacity basically dissipates at follow-up. The mean SGRQ score was 0.041 (0-0.104). The sequelae of survivors mainly included impaired sleep quality (17.1%), memory decline (26.8%), and anxiety (21.9%). After DLPE process, the lesion volume ratio decreased from 0.0018 (0.0003, 0.0353) at discharge to 0.0004 (0, 0.0032) at follow-up, p < 0.05, and the absorption ratio of lesion was 0.7147 (-1.0303, 0.9945). Conclusion: The ground-glass opacity of survivors had dissipated when they were discharged from hospital, and a little fibrosis was seen in CT after 6-month, mainly manifested as irregular lines, punctuate calcification and nodules. After DLPE and quantitative calculations, we found that the degree of fibrosis in the lungs of most survivors was mild, which basically did not affect lung function. However, there are a small number of patients with unabsorbed or increased fibrosis. Survivors mainly had non-pulmonary sequelae such as impaired sleep quality and memory decline. Pulmonary prognosis of Delta variant patients was better than original COVID-19, with fewer and milder sequelae.

The genetic basis and potential molecular mechanism of yellow-albino northern snakehead (Channa argus).

Body colour is an important economic trait for commercial fishes. Recently, a new colour morph displaying market-favoured yellow skin (termed as yellow-mutant, YM) of northern snakehead (Channa argus) was discovered in China. We confirmed that YM snakehead is an albino with complete loss of melanin in the skin and eyes by histological and ultrastructural observations, and inherited as a recessive Mendelian trait. By applying genomic analysis approaches, in combination with gene knockdown and rescue experiments, we suggested a non-sense mutation in slc45a2 (c.383G > A) is the causation for the YM snakehead. Notably, significantly higher levels of key melanogenesis genes (tyr, tyrp1, dct and pmel) and phospho-MITF protein were detected in YM snakehead than those in wild-type individuals, and the underlying mechanism was further investigated by comparative transcriptomic analysis. Results revealed that differential expressed genes involved in pathways like MAPK, WNT and calcium signalling were significantly induced in YM snakehead, which might account for the increased amount of melanogenesis elements, and presumably be stimulated by fibroblast-derived melanogenic factors in a paracrine manner. Our study clarified the genetic basis of colour variation in C. argus and provided the preliminary clue indicating the potential involvement of fibroblasts in pigmentation in fish.

VEGF-Expressing Mesenchymal Stem Cell Therapy for Safe and Effective Treatment of Pain in Parkinson's Disease.

Vascular endothelial growth factor (VEGF) is a pro-angiogenic factor that mediates the differentiation and function of vascular endothelial cells. VEGF has been implicated in modulating various pains. However, the effects of VEGF in Parkinson's disease (PD)-related pain have not been studied. The goal of this study was to understand the effects of VEGF-expressing mesenchymal stem cells (MSCs) on PD-related pain and the involved mechanisms. We used two types of MSCs: hAMSC-Vector-GFP and hAMSC-VEGF189-GFP in PD mice. Then, the expression of VEGF and the viability have been compared between two types of MSCs. To demonstrate the therapeutic effect of hAMSC-VEGF189-GFP, we transplanted each cell line in a PD mouse model. Head mechanical withdrawal thresholds were examined. hAMSC-VEGF189-GFP was associated with significantly increased VEGF expression and slightly increased viability, compared with hAMSC-Vector-GFP. The transplanted hAMSC-VEGF189-GFP significantly improved mechanical allodynia and inhibited transient receptor potential vanilloid 1 (TRPV1) expression in site. And such pain relief effects could be partially blocked by TRPV1 agonist. However, we did not observe tumor generation or neuron degeneration in hAMSC-VEGF189-GFP-transplanted animals. Taken together, our data suggest that hAMSC-VEGF189-GFP is safely therapeutically appropriate for treating PD-related pain. VEGF inhibits TRPV1 expression, which may contribute to its analgesic properties.

Identification and validation of key immune-related genes with promising diagnostic and predictive value in systemic sclerosis.

AIMS: To screen and confirm key immune-related genes (IRGs) with diagnostic and predictive value in systemic sclerosis (SSc) and provide potential therapeutic targets for patients with SSc. MATERIALS AND METHODS: In Gene Expression Omnibus database (GEO), four datasets of gene expression profiling related to SSc were downloaded and used for the analysis in this study. After differential analysis of SSc cases and controls in GSE130955, the differentially expressed genes (DEGs) were overlapped with IRGs to obtain the immune-related differentially expressed genes (IR-DEGs) in SSc. In addition, functional annotation and pathway enrichment of IR-DEGs were conducted. The protein-protein interaction network (PPI) was constructed to identify key IR-DEGs. Using GSE58095, GSE181549 and GSE130953, the diagnostic and predictive abilities for the key IR-DEGs in SSc were validated. Finally, the screened key genes were confirmed in skin derived bleomycin (BLM)-induced SSc mice by Real-time PCR. KEY FINDINGS: NGFR, TNFSF13B, FCER1G, GIMAP5, TYROBP and CSF1R may have important or very high diagnostic value for SSc. TYROBP and TNFSF13B had moderate and mild predictive value respectively in SSc patients after treatment. Real-time PCR assay further confirmed that the expressions of Ngfr, Tyrobp, Csf1r, Fcer1g and Gimap5 were significantly higher in skin of BLM-induced SSc mice than that in controls. SIGNIFICANCE: The key IR-DEGs, including NGFR, TNFSF13B, TYROBP, CSF1R, FCER1G and GIMAP5, may become auxiliary diagnostic indicators and potential biomarkers for SSc. Moreover, TNFSF13B and TYROBP could have good prospects as predictive indicators in SSc patients that accepted cyclophosphamide or transplantation therapy.

Mesenchymal stem cells for regenerative medicine in central nervous system.

Mesenchymal stem cells (MSCs) are multipotent stem cells, whose paracrine and immunomodulatory potential has made them a promising candidate for central nervous system (CNS) regeneration. Numerous studies have demonstrated that MSCs can promote immunomodulation, anti-apoptosis, and axon re-extension, which restore functional neural circuits. The therapeutic effects of MSCs have consequently been evaluated for application in various CNS diseases including spinal cord injury, cerebral ischemia, and neurodegenerative disease. In this review, we will focus on the research works published in the field of mechanisms and therapeutic effects of MSCs in CNS regeneration.

Flame-Retarded Rigid Polyurethane Foam Composites with the Incorporation of Steel Slag/Dimelamine Pyrophosphate System: A New Strategy for Utilizing Metallurgical Solid Waste.

Rigid polyurethane (RPUF) was widely used in external wall insulation materials due to its good thermal insulation performance. In this study, a series of RPUF and RPUF-R composites were prepared using steel slag (SS) and dimelamine pyrophosphate (DMPY) as flame retardants. The RPUF composites were characterized by thermogravimetric (TG), limiting oxygen index (LOI), cone calorimetry (CCT), and thermogravimetric infrared coupling (TG-FTIR). The results showed that the LOI of the RPUF-R composites with DMPY/SS loading all reached the combustible material level (22.0 vol%~27.0 vol%) and passed UL-94 V0. RPUF-3 with DMPY/SS system loading exhibited the lowest pHRR and THR values of 134.9 kW/m2 and 16.16 MJ/m2, which were 54.5% and 42.7% lower than those of unmodified RPUF, respectively. Additionally, PO· and PO2· free radicals produced by pyrolysis of DMPY could capture high energy free radicals, such as H·, O·, and OH·, produced by degradation of RPUF matrix, effectively blocking the free radical chain reaction of composite materials. The metal oxides in SS reacted with the polymetaphosphoric acid produced by the pyrolysis of DMPY in combustion. It covered the surface of the carbon layer, significantly insulating heat and mass transport in the combustion area, endowing RPUF composites with excellent fire performance. This work not only provides a novel strategy for the fabrication of high-performance RPUF composites, but also elucidates a method of utilizing metallurgical solid waste.

Biodecolorization and Ecotoxicity Abatement of Disperse Dye-Production Wastewater Treatment with Pycnoporus Laccase.

The biological treatment efficiency of dye wastewater using activated sludge (AS) is largely limited to the chromaticity and ecotoxicity of dyestuff. To alleviate this limitation, eleven industrial-grade disperse dyes were obtained from a fiber-dyeing factory, and for the first time, we studied the decolorization and detoxification effects of using the Pycnoporus laccase enzyme. Efficient decolorization was achieved with the following conditions: dye concentration 50 mg/L, 1-hydroxybenzotriazole (HBT) 0.15 mM, temperature 65 °C, pH 4, and laccase 0.33 U/mL. The decolorization rate of disperse dyes, ranging from 51 to 96% in this investigation, was highly dependent on the dye type, concentration, laccase loading, and HBT. The ecotoxicity of dyes was evaluated by studying the germination/growth of wheat seed as well as the respiratory rate of aerobic AS. Laccase treatment mitigated the phytotoxicity of dyes because of the higher wheat germination (e.g., increase of 38% for Black ECT 200%) and growth rate (e.g., increase of 91% for Blue 2BLN 200%). The reduced ecotoxicity of decolorized dye solution towards microorganisms was also confirmed by the finding that the oxygen uptake by aerobic AS was increased relative to that of the untreated samples (e.g., increase of 14 folds for Blue HGL 200%). In addition, the chemical oxygen demand (COD) of decolorized dye solution was slightly lower than that without decolorization during the respiratory test. The experimental results suggest that enzymatic decolorization and detoxification can be potentially used as a pretreatment method for disperse dye wastewater followed by AS treatment.

Cardiac ectopic lymphoid follicle formation in viral myocarditis involving the regulation of podoplanin in Th17 cell differentiation.

Autoimmunity contributes to the pathogenesis of viral myocarditis (VMC), which is characterized by the production of anti-heart autoantibodies (AHA) from lymphoid follicles. Recently, the formation of ectopic lymphoid follicles (ELFs) was reported in heart grafts. However, the existence and role of ELFs in myocardial tissues of VMC remain unclear. This study aimed to explore whether and how cardiac ELFs with germinal centers (GCs) could be generated during the development of VMC. We identified the existence of ELFs and explored the underlying mechanism. In a BALB/c mouse model of VMC, the dynamic myocardial infiltrations of lymphocytic aggregates and expressions of associated lymphorganogenic factors were investigated, accompanied by the detection of the production and location of myocardial AHA. The data indicated ELFs formation in myocardial tissues of VMC, and the number of ELFs was in accordance with the severity of VMC. Moreover, the functional ELFs with GCs were capable of facilitating the production of local AHA. Blocking IL-17 or podoplanin (PDPN) could inhibit cardiac ELFs generation, perhaps due to the negative regulation of PDPN neutralization in Th17 cell proliferation and differentiation. The presence of cardiac ELFs and AHA might offer new opportunities for stratification and early identification of VMC patients.

Rapid screening for safety of donation from donors with central nervous system malignancies.

With the increasing demand on organ transplants, it has become a common practice to include patients with primary central nervous system (CNS) malignancies as donors given the suggested low probability metastatic spread outside of the CNS. However, an extra-CNS spread of the disease cannot be excluded raising potential risks of cancer transmission from those donors. In order to balance between the risk of donor-derived disease transmission and the curative benefit for the recipient, a careful donor and organ selection is important. We performed a literature research and summarized all reported studies of organ transplants from donors suffered from primary CNS malignancies and determined the risk of tumor transmission to recipients. There were 22 cases of transplant-transmitted CNS tumors onto recipients since 1976. The association risks of cancer transmission were attributed to donor tumor histology, disruption of the blood-brain barrier, cerebrospinal fluid extra-CNS, and false diagnosis of primary intracranial tumor as well as the molecular properties of the primary tumor such as the existence of EGFR-amplification. The association risks and features of CNS tumors transmission recipients indicated that we need to reassess our thresholds for the potential fatal consequences of these donors.

GDNF Promotes Survival and Therapeutic Efficacy of Human Adipose-Derived Mesenchymal Stem Cells in a Mouse Model of Parkinson's Disease.

Mesenchymal stem cell (MSC)-based regenerative therapy is regarded as a promising strategy for the treatment of Parkinson's disease (PD). However, MSC components may exhibit poor intracranial survivability, particularly in the later stages following cell transplantation, limiting their potential curative effect and also clinical applications. Glial cell line-derived neurotrophic factor (GDNF), which encompasses a variety of transforming growth factor beta super family members, has been reported to enhance motor function and exert neuroprotective effects. However, no previous studies have investigated the effects of GDNF on human primary adipose-derived MSCs (hAMSCs), despite its potential for enhancing stem cell survival and promoting therapeutic efficacy in the treatment of PD. In the present study, we proposed a novel approach for enhancing the proliferative capacity and improving the efficacy of hAMSC treatment. Pre-exposure of engineered hAMSCs to GDNF enhanced the proliferation and differentiation of these stem cells in vitro. In addition, in 6-hydroxydopamine-lesioned mice, a common PD model, intracranial injection of hAMSCs-GDNF was associated with greater performance on behavioral tests, larger graft volumes 5 weeks after transplantation, and higher levels of Nestin, glial fibrillary acidic protein, and Tuj-1 differentiation than those treated with hAMSCs-Vector. Following transplantation of hAMSCs-GDNF into the striatum of lesioned models, we observed significant increases in tyrosine hydroxylase- and NeuN-positive staining. These findings highlight the therapeutic potential of hAMSCs-GDNF for patients with PD, as well as an efficient method for promoting therapeutic efficacy of these delivery vehicles.

Anisotropic Alginate Hydrogels Promote Axonal Growth across Chronic Spinal Cord Transections after Scar Removal.

We have previously reported that cell-seeded alginate hydrogels (AHs) with anisotropic capillaries can restore the continuity of the spinal cord and support axonal regeneration in a rat model of acute partial spinal cord transection. Whether similar effects can be found after transplantation into sites of complete chronic spinal cord transections without additional growth-promoting stimuli has not been investigated. We therefore implanted AHs into the cavity of a chronic thoracic transection following scar resection (SR) 4 weeks postinjury and examined electrophysiological and functional recovery as well as regeneration of descending and ascending projections within and beyond the AH scaffold up to 3 months after engraftment. Our results indicate that both electrophysiological conductivity and locomotor function are significantly improved after AH engraftment. SR transiently impairs locomotor function immediately after surgery but does not affect long-term outcomes. Histological analysis shows numerous host cells migrating into the scaffold channels and a reduction of fibroglial scaring around the lesion by AH grafts. In contrast to corticospinal axons, raphaespinal and propriospinal descending axons and ascending sensory axons regenerate throughout the scaffolds and extend into the distal host parenchyma. These results further support the pro-regenerative properties of AHs and their therapeutic potential for chronic SCI in combination with other strategies to improve functional outcomes after spinal cord injury.

Sensation of TRPV1 via 5-hydroxytryptamine signaling modulates pain hypersensitivity in a 6-hydroxydopamine induced mice model of Parkinson's disease.

Parkinson's disease (PD) related pain can be assigned to either nociceptive pain or neuropathic pain, in which Transient receptor potential vanilloid 1 (TRPV1) has been demonstrated to play a pivotal role. Yet little research has examined possible involvement of TRPV1 in pain in PD. Here, we show that TRPV1 is highly expressed in PD and blocking TRPV1 can alleviate pain in PD. The level of TRPV1 in 6-OHDA induced semi mice model of PD was evaluated. The effect of TRPV1 and involved serotonin (5-HT) was also examined in the model. Unilateral injection of 6-OHDA in striatum significantly decreased thermal pain threshold and induced mechanical allodynia without changes in conditioned place preference. Immunostaining revealed that great increased expression in TRPV1 in the Vc of 6-OHDA lesioned mice compared with sham mice. TRPV1 sensitization was maintained by 5-HT/5-HT3A. In 6-OHDA-lesioned mice model of PD, TRPV1 sensitization might be implicated in the maintenance of behavioral hypersensitivity by enhanced descending 5-HT pain facilitation and dorsal horn 5-HT3AR mechanism.