CXCR7 activation evokes the anti-PD-L1 antibody against glioblastoma by remodeling CXCL12-mediated immunity.

The interaction between glioblastoma cells and glioblastoma-associated macrophages (GAMs) influences the immunosuppressive tumor microenvironment, leading to ineffective immunotherapies. We hypothesized that disrupting the communication between tumors and macrophages would enhance the efficacy of immunotherapies. Transcriptomic analysis of recurrent glioblastoma specimens indicated an enhanced neuroinflammatory pathway, with CXCL12 emerging as the top-ranked gene in secretory molecules. Single-cell transcriptome profiling of naïve glioblastoma specimens revealed CXCL12 expression in tumor and myeloid clusters. An analysis of public glioblastoma datasets has confirmed the association of CXCL12 with disease and PD-L1 expression. In vitro studies have demonstrated that exogenous CXCL12 induces pro-tumorigenic characteristics in macrophage-like cells and upregulated PD-L1 expression through NF-κB signaling. We identified CXCR7, an atypical receptor for CXCL12 predominantly present in tumor cells, as a negative regulator of CXCL12 expression by interfering with extracellular signal-regulated kinase activation. CXCR7 knockdown in a glioblastoma mouse model resulted in worse survival outcomes, increased PD-L1 expression in GAMs, and reduced CD8+ T-cell infiltration compared with the control group. Ex vivo T-cell experiments demonstrated enhanced cytotoxicity against tumor cells with a selective CXCR7 agonist, VUF11207, reversing GAM-induced immunosuppression in a glioblastoma cell-macrophage-T-cell co-culture system. Notably, VUF11207 prolonged survival and potentiated the anti-tumor effect of the anti-PD-L1 antibody in glioblastoma-bearing mice. This effect was mitigated by an anti-CD8ß antibody, indicating the synergistic effect of VUF11207. In conclusion, CXCL12 conferred immunosuppression mediated by pro-tumorigenic and PD-L1-expressing GAMs in glioblastoma. Targeted activation of glioblastoma-derived CXCR7 inhibits CXCL12, thereby eliciting anti-tumor immunity and enhancing the efficacy of anti-PD-L1 antibodies.

Surgical excision and radiotherapy for brain metastasis from colorectal cancer: How frailty and comorbidity indices influence outcome.

The incidence of brain metastasis (BM) from colorectal cancer (CRC) is increasing. This study aims to identify the clinical prognosticators and evaluate the prognostic validity of common comorbidity indices in patients with BM from CRC. This retrospective single-center study analyzed 93 patients with BM from CRC who received surgical excision and/or radiotherapy. The clinical characteristics and prognostic indices including the 5-item modified frailty index (mFI-5) and prognostic nutritional index (PNI) were calculated from the collected patient data and analyzed. In this study, 66 (71.0%), 10 (10.8%), and 17 (18.3%) patients received whole-brain radiotherapy (WBRT) alone, surgery alone, and surgery plus WBRT, respectively. The median survival of all patients was 3.98 months (IQR: 1.74-7.99). The 2- and 3-year survival rates were 7.4% and 3.7%, respectively. Controlled primary tumor (p = 0.048), solitary BM (p = 0.001), surgery + radiation (p < 0.001), and greater PNI (p = 0.001) were independent predictors of favorable survival. In surgically treated patients, uncontrolled primary tumor (p = 0.006), presence of multiple BM (p < 0.001), and MFI-5 ≥ 2 (p = 0.038) were independent prognosticators. For patients who received WBRT, the presence of two (p = 0.004) or multiple (p < 0.001) BM and PNI (p < 0.001) were independent survival predictors MFI-5, multiple BM, and the status of the primary tumor were independent prognosticators for patients who underwent surgery for CRCBM. For patients who received WBRT, the PNI and the number of BM were independent survival predictors.

Effects of an ice roller on chronic kidney disease-associated pruritus in patients receiving haemodialysis.

BACKGROUND: Chronic kidney disease-associated pruritus is a distressing symptom and has a far-reaching impact on patients' sleep and quality of life for most patients receiving haemodialysis. Traditional therapies have limited effectiveness. OBJECTIVES: This study aimed to invent a self-operated ice roller and evaluate its efficacy in relieving pruritus, sleep quality, and quality of life. DESIGN: This study was experimental with a two-arm parallel group design. PARTICIPANTS: A convenient sampling method was used to recruit 60 patients receiving haemodialysis who reported pruritus (5D-Itch Scale score >5) lasting over 4 weeks in Taiwan. The participants were randomly assigned to one of two groups: the intervention group used an ice roller for 7 days, while the control group received no anti-pruritus treatment. MEASUREMENTS: This study was experimental with a two-arm parallel group design. The measurement instruments included the 5D-Itch Scale, Pittsburgh Sleep Quality Index and WHOQOL-BREF-Taiwan Version. The analysis of covariance, chi-square, Independent t tests, and partial Eta2 (η2 p) were used to analyse the data. RESULTS: The participants' mean age was 62.77 years. Application of the ice roller significantly decreased overall pruritus (p < .05; η2 p = .09) and distribution of pruritus-associated bodily parts (p = .03; η2 p = .08). There were no statistically significant differences in sleep quality and related indicators between the experimental and control groups at the study endpoint. Regarding quality of life, only the social relationship domain significantly differed between the two groups (p = .02; η2 p = .08). CONCLUSIONS: The ice roller can decrease pruritus and its distribution in patients receiving haemodialysis, serving as an adjunct therapy alongside conventional anti-pruritus treatments.

Simple coiling of middle meningeal artery embolization for chronic subdural hematoma: An inverse probability of treatment weighting matched cohort study.

BACKGROUND: Middle meningeal artery embolization (MMAE) for chronic subdural hematoma (CSDH) has gained much attention in recent years. However, unintended embolization may occur when employing liquid embolic agents or particles. We present our clinical experience in simple coiling of MMAE to manage CSDH. METHODS: Patients underwent either surgical evacuation or MMAE with simple coiling for CSDH were reviewed. Clinical and radiographic outcomes were assessed at admission, 1-month, and 6-month intervals. Two treatment groups were matched with inverse probability of treatment weighting. RESULTS: One hundred twelve patients were included, with 27 patients in MMAE group and 87 patients in surgery group. In MMAE group, significant reductions were observed in hematoma width (admission vs. 1-month, 2.04 [1.44-2.60] cm vs. 0.62 [0.37-0.95] cm, p < 0.001). The adjusted odds ratio (aOR) of surgical rescue rate (0.77 95%CI 0.13-4.47, p = 0.77), hematoma reduction (>50%) (0.21 95%CI 0.04-1.07, p = 0.06), and midline shift improvement rate (3.22, 95%CI 0.84-12.4, p = 0.09) had no substantial disparities between two groups at 1-month follow-up. In addition, no significant difference was noted between two groups in terms of hematoma reduction (>50%) at 6-month follow-up (aOR 1.09 95%CI 0.32-3.70, p = 0.89). No procedure-related complications were found in MMA embolization group. CONCLUSION: Simple coiling for MMA had comparable outcomes with surgical evacuation for CSDH. Our findings suggest that simple coiling can be an alternative choice for liquid agents or particles in MMA embolization for CSDH with acceptable safety.

Decompressive Craniectomy versus Craniotomy for Acute Subdural Hematoma: Updated meta-analysis of real-world clinical outcome after RESCUE-ASDH trial.

INTRODUCTION: The RESCUE-ASDH trial found that disability and quality-of-life outcomes were similar between craniotomy and decompressive craniectomy for traumatic acute subdural hematoma, contrasting previous literature. This meta-analysis aims to validate the applicability of RESCUE-ASDH results using real-world data in acute subdural hematoma patients. METHODS: We searched Chocrane, Embase, and MEDLINE for relevant articles reporting clinical outcomes of craniotomy and decompressive craniectomy. Meta-analysis utilized R software with the restricted maximum likelihood method for random-effects meta-analyses, presenting odds ratios and 95% confidence intervals with Hartung-Knapp-Sidik-Jonkman adjustment for heterogeneity. RESULTS: Besides RESCUE-ASDH, 5 retrospective studies were included, spanning 2006-2016. A total of 961 patients with traumatic ASDH were included in this study (Craniotomy = 467; Decompressive craniotomy = 494). The pooled analysis of retrospective studies showed no significant difference in poor clinical outcomes between the two groups (OR 0.59, 95% CI, 0.32 to 1.10). These findings align with the RESCUE-ASDH trial (OR 0.84, 95% CI, 0.58 to 1.23). Mortality rate was significant higher in patients undergoing craniectomy in pooled result of retrospective studies (OR 0.59, 95% CI, 0.32 to 1.10). In RESCUE-ASDH trial, reoperation rate was higher in the craniotomy group, but the pooled result of retrospective did not show significant difference between the craniotomy and craniectomy group. CONCLUSIONS: This real-world evidence confirms the RESCUE-ASDH trial results. Both craniotomy and decompressive craniectomy yielded similar disability and quality-of-life outcomes for traumatic acute subdural hematoma patients. LEVEL OF EVIDENCE: Level 2, Systematic and meta-analysis.

Systematic Review and Meta-analysis of Radial or Femoral Access for Carotid Stenting.

PURPOSE: There is a growing interest in performing coronary artery and neurovascular interventions via the radial artery; however, few studies have examined the outcomes of transradial carotid stenting. Therefore, our study aimed to compare cerebrovascular outcomes and crossover rates in carotid stenting between transradial and traditional transfemoral approaches. METHODS: A systematic review was performed by searching three electronic databases from inception to June 2022 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. In addition, random effect meta-analysis was used to pool the odds ratios (ORs) for stroke, transient ischemic attack, major adverse cardiac events, death, major vascular access site complications, and procedure crossover rates between the transradial and transfemoral approaches. RESULTS: A total of 6 studies were included involving a total of n = 567 transradial and n = 6176 transfemoral procedures. The ORs for stroke, transient ischemic attack, and major adverse cardiac events were 1.43 (95% confidence interval, CI 0.72-2.86, I2 = 0), 0.51 (95% CI 0.17-1.54, I2 = 0), and 1.08 (95% CI 0.62-1.86, I2 = 0), respectively. Neither the major vascular access site complication rate (OR 1.11, 95% CI 0.32-3.87, I2 = 0) nor crossover rate (OR 3.94, 95% CI 0.62-25.11, I2 = 57%) showed statistically significant differences between the two approaches. CONCLUSION: The modest quality of the data suggested comparable procedural outcomes between the transradial and transfemoral approaches when performing carotid stenting; however, high level evidence regarding postoperative brain images and risk of stroke in transradial carotid stenting are lacking. Therefore, it is reasonable for interventionists to weigh up the risks of neurological events and potential benefits, including fewer access site complications, before choosing the radial or femoral arteries as access sites. Future large-scale randomized controlled trials are imperative.

Outcomes of surgery and subsequent therapy for central nervous system oligoprogression in EGFR-mutated NSCLC patients.

BACKGROUND: Oligoprogression is an emerging issue in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, the surgical treatment for central nervous system (CNS) oligoprogression is not widely discussed. We investigated the outcomes of craniotomy with adjuvant whole-brain radiotherapy (WBRT) and subsequent therapies for CNS oligoprogression in patients with EGFR-mutated NSCLC. METHODS: NSCLC patients with CNS oligoprogression were identified from a tertiary medical center. The outcomes of surgery with adjuvant WBRT or WBRT alone were analyzed, along with other variables. Overall survival and progression-free survival were analyzed using the log-rank test as the primary and secondary endpoints. A COX regression model was used to identify the possible prognostic factors. RESULTS: Thirty-seven patients with CNS oligoprogression who underwent surgery or WBRT were included in the study after reviewing 728 patients. Twenty-one patients underwent surgery with adjuvant WBRT, and 16 received WBRT alone. The median overall survival for surgery and WBRT alone groups was 43 (95% CI 17-69) and 22 (95% CI 15-29) months, respectively. Female sex was a positive prognostic factor for overall survival (OR 0.19, 95% CI 0.06-0.57). Patients who continued previous tyrosine kinase inhibitors (OR 3.48, 95% CI 1.06-11.4) and induced oligoprogression (OR 3.35, 95% CI 1.18-9.52) were associated with worse overall survival. Smoking history (OR 4.27, 95% CI 1.54-11.8) and induced oligoprogression (OR 5.53, 95% CI 2.1-14.7) were associated with worse progression-free survival. CONCLUSIONS: Surgery combined with adjuvant WBRT is a feasible treatment modality for CNS oligoprogression in patients with EGFR-mutated NSCLC. Changing the systemic-targeted therapy after local treatments may be associated with improved overall survival.

Characterizing the Impact of Compression Duration and Deformation-Related Loss of Closure Force on Clip-Induced Spinal Cord Injury in Rats.

The clip-induced spinal cord injury (SCI) rat model is pivotal in preclinical SCI research. However, the literature exhibits variability in compression duration and limited attention to clip deformation-related loss of closure force. We aimed to investigate the impact of compression duration on SCI severity and the influence of clip deformation on closure force. Rats received T10-level clip-induced SCI with durations of 1, 5, 10, 20, and 30 s, and a separate group underwent T10 transection. Outcomes included functional, histological, electrophysiological assessments, and inflammatory cytokine analysis. A tactile pressure mapping system quantified clip closure force after open-close cycles. Our results showed a positive correlation between compression duration and the severity of functional, histological, and electrophysiological deficits. Remarkably, even a brief 1-s compression caused significant deficits comparable to moderate-to-severe SCI. SSEP waveforms were abolished with durations over 20 s. Decreased clip closure force appeared after five open-close cycles. This study offers critical insights into regulating SCI severity in rat models, aiding researchers. Understanding compression duration and clip fatigue is essential for experiment design and interpretation using the clip-induced SCI model.

Endovascular treatment in bilateral cavernous sinus dural arteriovenous fistulas: a systematic review and meta-analysis.

Few studies have discussed the disease nature and treatment outcomes for bilateral cavernous sinus dural arteriovenous fistula (CSDAVF). This study aimed to investigate the clinical features and treatment outcomes of bilateral CSDAVF. Embase, Medline, and Cochrane library were searched for studies that specified the outcomes of bilateral CSDAVF from inception to April 2022. The classification, clinical presentation, angiographic feature, surgical approach, and treatment outcomes were collected. Meta-analysis was performed using the random effects model. Eight studies reporting 97 patients were included. The clinical presentation was mainly orbital (n = 80), cavernous (n = 52) and cerebral (n = 5) symptoms. The most approached surgical route was inferior petrosal sinus (n = 80), followed by superior orbital vein (n = 10), and alternative approach (n = 7). Clinical symptoms of 88% of the patients (95% CI 80-93%, I2 = 0%) were cured, and 82% (95% CI 70-90%, I2 = 7%) had angiographic complete obliteration of fistulas during follow up. The overall complication rate was 18% (95% CI 11-27%, I2 = 0%). Therefore, endovascular treatment is an effective treatment for bilateral CSDAVF regarding clinical or angiographic outcomes. However, detailed evaluation of preoperative images and comprehensive surgical planning of the approach route are mandatory owing to complexity of the lesions.

Validation of an Automated Cardiothoracic Ratio Calculation for Hemodialysis Patients.

Cardiomegaly is associated with poor clinical outcomes and is assessed by routine monitoring of the cardiothoracic ratio (CTR) from chest X-rays (CXRs). Judgment of the margins of the heart and lungs is subjective and may vary between different operators. METHODS: Patients aged > 19 years in our hemodialysis unit from March 2021 to October 2021 were enrolled. The borders of the lungs and heart on CXRs were labeled by two nephrologists as the ground truth (nephrologist-defined mask). We implemented AlbuNet-34, a U-Net variant, to predict the heart and lung margins from CXR images and to automatically calculate the CTRs. RESULTS: The coefficient of determination (R2) obtained using the neural network model was 0.96, compared with an R2 of 0.90 obtained by nurse practitioners. The mean difference between the CTRs calculated by the nurse practitioners and senior nephrologists was 1.52 ± 1.46%, and that between the neural network model and the nephrologists was 0.83 ± 0.87% (p < 0.001). The mean CTR calculation duration was 85 s using the manual method and less than 2 s using the automated method (p < 0.001). CONCLUSIONS: Our study confirmed the validity of automated CTR calculations. By achieving high accuracy and saving time, our model can be implemented in clinical practice.

Quantification of vessel separation using the carotid-jugular angle to predict the nerve origin of neck peripheral nerve sheath tumours: a pooled analysis of cases from the literature and a single-center cohort.

BACKGROUND: Postoperative nerve palsy is a major complication following resection of neck peripheral nerve sheath tumours (PNSTs). Accurate preoperative identification of the nerve origin (NO) can improve surgical outcomes and patient counselling. MATERIAL AND METHODS: This study was a retrospective cohort and quantitative analysis of the literature. The authors introduced a parameter, the carotid-jugular angle (CJA), to differentiate the NO. A literature review of neck PNST cases from 2010 to 2022 was conducted. The CJA was measured from eligible imaging data, and quantitative analysis was performed to evaluate the ability of the CJA to predict the NO. External validation was performed using a single-centre cohort from 2008 to 2021. RESULTS: In total, 17 patients from our single-centre cohort and 88 patients from the literature were analyzed. Among them, 53, 45, and 7 patients had sympathetic, vagus, and cervical nerve PNSTs, respectively. Vagus nerve tumours had the largest CJA, followed by sympathetic tumours, whereas cervical nerve tumours had the smallest CJA ( P <0.001). Multivariate logistic regression identified a larger CJA as a predictor of vagus NO ( P <0.001), and receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.907 (0.831-0.951) for the CJA to predict vagus NO ( P <0.001). External validation showed an AUC of 0.928 (0.727-0.988) ( P <0.001). Compared with the AUC of the previously proposed qualitative method (AUC=0.764, 0.673-0.839), that of the CJA was greater ( P =0.011). The cut-off value identified to predict vagus NO was greater than or equal to 100°. Receiver operating characteristic analysis showed an AUC of 0.909 (0.837-0.956) for the CJA to predict cervical NO ( P <0.001), with a cut-off value less than 38.5°. CONCLUSIONS: A CJA greater than or equal to 100° predicted a vagus NO and a CJA less than 100° predicted a non-vagus NO. Moreover, a CJA less than 38.5 was associated with an increased likelihood of cervical NO.

Evaluation of the safety, radiographic and resident training results of thoracic pedicle screws placement using resection of the transverse process.

OBJECTIVE: This study aimed at the evaluation and assessment of a simple method, the transverse process resection (TPR) technique, for freehand thoracic pedicle screw placement and the learning curve for trainee surgeons. METHODS: In the TPR technique, the tip of the thoracic transverse process (TP) is removed to create an entry point in the cancellous bone of the TP, and the thoracic pedicle is cannulated from the TP. We retrospectively evaluated the safety and radiographic results of the TPR technique and compared with that of conventional pedicle screws. The training performance of seven neurosurgical residents with TPR techniques were evaluated. RESULTS: Among 46 patients, a total of 322 thoracic screws were analyzed, including 178 screws placed using the TPR technique and 144 screws using the conventional straight-forward (SF) technique. TPR screws had greater medial angulations in all levels from T2 to T12 compared to SF screws (p < 0.001). The incidence of pedicle breach was lower in the TPR screws compared to SF screws (6.2% vs. 21.5%, p < 0.001), especially for screws placed by residents (6.7% vs. 29.6%, p < 0.001). Residents had improved performance following a cadaveric training course on the TPR technique (p = 0.001). CONCLUSION: This study demonstrated the safety of the TPR technique for thoracic pedicle screw placement and its short learning curve for trainee surgeons.

Symptom perception and self-care practice for uraemic pruritus in patients receiving haemodialysis.

BACKGROUND: Due to the recurrent nature of uraemic pruritus among patients receiving haemodialysis, self-care can offer patients a means to ameliorate this symptom. Qualitative data on self-care of uraemic pruritus are limited. OBJECTIVE: To explore how patients on haemodialysis perceive uraemic pruritus, implement self-care practice, and appraise the outcome of self-caring uraemic pruritus. DESIGN: The Common Sense Model of Self-Regulation guided the study design. PARTICIPANTS AND APPROACHES: Data were collected through face-to-face interviews with 30 patients receiving haemodialysis who were aged from 50 to 89 years and had had uraemic pruritus for more than 6 weeks. Interviews were audio recorded, and verbatim transcriptions of interviews were analysed. FINDINGS: Our participants generally used life-related analogies to describe uraemic pruritus, which they reviewed as a momentarily controllable symptom with an endless timeline. Most participants reported limited knowledge of the aetiology and multifaceted impacts of uraemic pruritus on their daily life and emotional status. The impacts on daily life included decreased zest for activities and sleep disturbances. Physical management of uraemic pruritus involved daily substance use and interventions employed during pruritic episodes. Psychological managements involved preferences for indoor activities and a fatalistic outlook. Unsatisfactory outcomes and psychological burdens from self-care practice were reported. CONCLUSIONS: Life experiences shape symptom presentation and self-care practice in patients on haemodialysis. The modalities for self-caring for uraemic pruritus are diverse but not remarkably effective. Performing self-care tasks places a substantial burden on patients. Individualised educational programs should be developed to improve the outcome of self-care practice.

SH3GLB1-related autophagy mediates mitochondrial metabolism to acquire resistance against temozolomide in glioblastoma.

BACKGROUND: The mechanism by which glioblastoma evades temozolomide (TMZ)-induced cytotoxicity is largely unknown. We hypothesized that mitochondria plays a role in this process. METHODS: RNA transcriptomes were obtained from tumor samples and online databases. Expression of different proteins was manipulated using RNA interference or gene amplification. Autophagic activity and mitochondrial metabolism was assessed in vitro using the respective cellular and molecular assays. In vivo analysis were also carried out in this study. RESULTS: High SH3GLB1 gene expression was found to be associated with higher disease grading and worse survival profiles. Single-cell transcriptome analysis of clinical samples suggested that SH3GLB1 and the altered gene levels of oxidative phosphorylation (OXPHOS) were related to subsets expressing a tumor-initiating cell signature. The SH3GLB1 protein was regulated by promoter binding with Sp1, a factor associated with TMZ resistance. Downregulation of SH3GLB1 resulted in retention of TMZ susceptibility, upregulated p62, and reduced LC3B-II. Autophagy inhibition by SH3GLB1 deficiency and chloroquine resulted in attenuated OXPHOS expression. Inhibition of SH3GLB1 in resistant cells resulted in alleviation of TMZ-enhanced mitochondrial metabolic function, such as mitochondrial membrane potential, mitochondrial respiration, and ATP production. SH3GLB1 modulation could determine tumor susceptibility to TMZ. Finally, in animal models, resistant tumor cells with SH3GLB1 knockdown became resensitized to the anti-tumor effect of TMZ, including the suppression of TMZ-induced autophagy and OXPHOS. CONCLUSIONS: SH3GLB1 promotes TMZ resistance via autophagy to alter mitochondrial function. Characterizing SH3GLB1 in glioblastoma may help develop new therapeutic strategies against this disease in the future.

Sciatic nerve stimulation alleviates acute neuropathic pain via modulation of neuroinflammation and descending pain inhibition in a rodent model.

BACKGROUND: Neuropathic pain (NP) is characterized by abnormal activation of pain conducting pathways and manifests as mechanical allodynia and thermal hypersensitivity. Peripheral nerve stimulation is used for treatment of medically refractory chronic NP and has been shown to reduce neuroinflammation. However, whether sciatic nerve stimulation (SNS) is of therapeutic benefit to NP remains unclear. Moreover, the optimal frequency for SNS is unknown. To address this research gap, we investigated the effect of SNS in an acute NP rodent model. METHODS: Rats with right L5 nerve root ligation (NRL) or Sham surgery were used. Ipsilateral SNS was performed at 2 Hz, 20 Hz, and 60 Hz frequencies. Behavioral tests were performed to assess pain and thermal hypersensitivity before and after NRL and SNS. Expression of inflammatory proteins in the L5 spinal cord and the immunohistochemical alterations of spinal cord astrocytes and microglia were examined on post-injury day 7 (PID7) following NRL and SNS. The involvement of the descending pain modulatory pathway was also investigated. RESULTS: Following NRL, the rats showed a decreased pain threshold and latency on the von Frey and Hargreaves tests. The immunofluorescence results indicated hyperactivation of superficial spinal cord dorsal horn (SCDH) neurons. Both 2-Hz and 20-Hz SNS alleviated pain behavior and hyperactivation of SCDH neurons. On PID7, NRL resulted in elevated expression of spinal cord inflammatory proteins including NF-κB, TNF-α, IL-1ß, and IL-6, which was mitigated by 2-Hz and 20-Hz SNS. Furthermore, 2-Hz and 20-Hz SNS suppressed the activation of spinal cord astrocytes and microglia following NRL on PID7. Activity of the descending serotoninergic pain modulation pathway showed an increase early on PID1 following 2-Hz and 20-Hz SNS. CONCLUSIONS: Our results support that both 2-Hz and 20-Hz SNS can alleviate NP behaviors and hyperactivation of pain conducting pathways. We showed that SNS regulates neuroinflammation and reduces inflammatory protein expression, astrocytic gliosis, and microglia activation. During the early post-injury period, SNS also facilitates the descending pain modulatory pathway. Taken together, these findings support the therapeutic potential of SNS for acute NP.

Disrupted cellular calcium homeostasis is responsible for Aß-induced learning and memory damage and lifespan shortening in a model of Aß transgenic fly.

Accumulated Aß is one of the hallmarks of Alzheimer's disease. Although accumulated results from in vivo and in vitro studies have shown that accumulated Aß causes learning and memory deficit, cell death, and lifespan reduction, the underlying mechanism remains elusive. In neurons, calcium dynamics is regulated by voltage-gated calcium channel (VGCC) and endoplasmic reticulum and is important for neuron survival and formation of learning and memory. The current study employs in vivo genetics to reveal the role of calcium regulation systems in Aß-induced behavioral damage. Our data shows that although increased VGCC improves learning and memory in Aß42 flies, reduction of VGCC and Inositol trisphosphate receptors extends Aß42 flies' lifespan and improves cell viability. The complex role of calcium regulation systems in Aß-induced damage suggests that the imbalance of calcium dynamic is one of the main factors to trigger learning and memory deficit and cell death in the disease.

Mitochondrial Transplantation Attenuates Neural Damage and Improves Locomotor Function After Traumatic Spinal Cord Injury in Rats.

Mitochondrial dysfunction is a hallmark of secondary neuroinflammatory responses and neuronal death in spinal cord injury (SCI). Even though mitochondria-based therapy is an attractive therapeutic option for SCI, the efficacy of transplantation of allogeneic mitochondria in the treatment of SCI remains unclear. Herein, we determined the therapeutic effects of mitochondrial transplantation in the traumatic SCI rats. Compressive SCI was induced by applying an aneurysm clip on the T10 spinal cord of rats. A 100-µg bolus of soleus-derived allogeneic mitochondria labeled with fluorescent tracker was transplanted into the injured spinal cords. The results showed that the transplanted mitochondria were detectable in the injured spinal cord up to 28 days after treatment. The rats which received mitochondrial transplantation exhibited better recovery of locomotor and sensory functions than those who did not. Both the expression of dynamin-related protein 1 and severity of demyelination in the injured cord were reduced in the mitochondrial transplanted groups. Mitochondrial transplantation also alleviated SCI-induced cellular apoptosis and inflammation responses. These findings suggest that transplantation of allogeneic mitochondria at the early stage of SCI reduces mitochondrial fragmentation, neuroapoptosis, neuroinflammation, and generation of oxidative stress, thus leading to improved functional recovery following traumatic SCI.

Cedrus atlantica extract exerts antiproliferative effect on colorectal cancer through the induction of cell cycle arrest and apoptosis.

Cedrus atlantica is a tree species found in Morocco with many clinical benefits in genitourinary, musculoskeletal, and skin systems. Previous studies have reported that extracts of Cedrus atlantica have antioxidant, antimicrobial, and anticancer properties. However, its role in colorectal cancer (CRC) remains unclear. The present study investigated the effects and underlying mechanisms of Cedrus atlantica extract (CAt) using HT-29 (human colorectal adenocarcinoma) and CT-26 CRC cell lines. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to measure cell viability. Flow cytometry analysis and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay were used to study the cell cycle and cell apoptosis, respectively. The expression of cell cycle and apoptosis-associated proteins was detected by western blotting or immunohistochemical (IHC) staining. CAt showed significant inhibitory effects on the proliferation of HT-29 and CT-26 cells, and combined with the clinical drug, 5-fluorouracil (5-FU), exhibited synergistic effects. CAt induced cell cycle arrest at the G0/G1 phase through the upregulation of p53/p21 and the downregulation of cyclin-dependent kinases (CDKs)/cyclins. In addition, CAt-treated cells exhibited chromatin condensation, DNA fragmentation, and apoptotic bodies, which are typical characteristics of apoptosis activated via both the extrinsic (Fas ligand (FasL)/Fas/caspase-8) and intrinsic (Bax/caspase-9) pathways. Importantly, CAt suppressed tumor progression and prolonged the life span of mice within a well-tolerated dose. Therefore, our findings provide novel insights into the use of CAt for the treatment of CRC.

Outcome of Wingspan Stent Using Aggressive Post-stent Balloon Dilation for Intracranial Atherosclerosis Stenosis.

Background: Wingspan stent has gained interest for better long-term outcomes for intracranial atherosclerosis disease (ICAD). However, in-stent restenosis still presents as a problem and may cause postoperative neurological events. We aimed to find a way to prevent in-stent restenosis. Method: Patients with stenosis >70% ICAD were treated with wingspan stent and were retrospectively reviewed. The patients were separated into two groups: one with post-dilation and the other without post-dilation. The outcomes of wingspan stenting were compared immediately after the surgery and at a 1-year follow-up. Results: Overall, 28 patients were included for analysis, with 15 patients undergoing post-dilation and 13 patients not undergoing the procedure. The extent of stenosis was significantly lower in the post-dilation group than in the no post-dilation group, both immediately after the surgery (14.8 ± 10.2 vs. 28.5 ± 14.5%, p < 0.01) and at 1-year follow-up (25.8 ± 18.0 vs. 50.1 ± 23.2%, p < 0.01). The post-dilation method immediately expanded the stent diameter (2.89 ± 0.48 vs. 3.05 ± 0.44 mm, p < 0.001), and the diameter still increased at 1-year follow-up (3.05 ± 0.44 vs. 3.12 ± 0.43 mm, p < 0.01) due to the self-expandable property of the wingspan. Similarly, in the no post-dilation group, the stent size was also increased (2.70 ± 0.67 vs. 2.80 ± 0.64 mm, p < 0.01). However, at 1-year follow up, the luminal diameter was stationary in the post-dilation group (2.36 ± 0.73 vs. 2.46 ± 0.82 mm, p = 0.88) and decreased in the no post-dilation group (2.24 ± 0.56 vs. 1.60 ± 0.79 mm, p < 0.01). The periprocedural complication rate was similar between the groups. Conclusion: The post-dilation method can be feasibly performed and can offer better stent expansion and apposition in the wingspan system. By applying this technique, we might prevent in-stent restenosis and improve neurological outcomes.