Background Stroke patients with dysphagia and family caregivers will experience multiple transitions during the whole process of the disease and various nursing needs will be generated. There is a lack of knowledge about their experiences at different transition stages. Thus, we aimed to explore the transition experiences of patients with post stroke dysphagia and family caregivers from admission to discharge home. Methods A semi-structured interview based on Meleis’s transition theory was used during hospitalization and telephone follow-up interviews were conducted in the first, third, and sixth month after the diagnosis of dysphagia. Interview transcripts were analyzed using the conventional content analysis method. Results A total of 17 participants enrolled in the first face-to-face interview, 16 participants took part in the first month’s telephone follow-up interview, 14 participants in the third month, and 12 participants in the sixth month. The transition experiences of patients with post stroke dysphagia and family caregivers could be summarized into three themes: (1)transition from onset to admission; (2)transition from discharge to other rehabilitation institutions; and (3)transition from discharge to home. Each theme had identified interrelated subthemes. Conclusions The experiences of patients with post stroke dysphagia and family caregivers during transition are a dynamic process with enormous challenges in each phase. Collaboration with health care professionals, follow-up support after discharge, and available community and social support should be integrated into transitional nursing to help patients facilitate their transition.

Spinal cord injury (SCI) treatment remains a major challenge. Spinal motor neurons (MNs) are seriously injured in the early stage after SCI, but this has not received sufficient attention. Oxidative stress is known to play a crucial role in SCI pathology. Our studies demonstrated that oxidative stress can cause severe damage to the cytoskeleton of spinal MNs. Docosahexaenoic acid (DHA) has been shown to have beneficial effects on SCI, but the mechanism remains unclear, and no study has investigated the effect of DHA on oxidative stress-induced spinal MN injury. Here, we investigated the effect of DHA on spinal MN injury through in vivo and in vitro experiments, focusing on the cytoskeleton. We found that DHA not only promoted spinal MN survival but, more importantly, alleviated the severe cytoskeletal destruction of these neurons induced by oxidative stress in vitro and in mice with SCI in vivo. In addition, the mechanisms involved were investigated and elucidated. These results not only suggested a beneficial role of DHA in spinal MN cytoskeletal destruction caused by oxidative stress and SCI but also indicated the important role of the spinal MN cytoskeleton in the recovery of motor function after SCI. Our study provides new insights for the formulation of SCI treatment.

BACKGROUND/AIM:Efficient discharge for stroke patients is crucial but challenging. The study aimed to develop early predictive models to explore which patient characteristics and variables significantly influence the discharge planning of patients, based on the data available within 24 h of admission. DESIGN:Prospective observational study. METHODS:A prospective cohort was conducted at a university hospital with 523 patients hospitalised for stroke. We built and trained six different machine learning (ML) models, followed by testing and tuning those models to find the best-suited predictor for discharge disposition, dichotomized into home and non-home. To evaluate the accuracy, reliability and interpretability of the best-performing models, we identified and analysed the features that had the greatest impact on the predictions. RESULTS:In total, 523 patients met the inclusion criteria, with a mean age of 61 years. Of the patients with stroke, 30.01% had non-home discharge. Our model predicting non-home discharge achieved an area under the receiver operating characteristic curve of 0.95 and a precision of 0.776. After threshold was moved, the model had a recall of 0.809. Top 10 variables by importance were National Institutes of Health Stroke Scale (NIHSS) score, family income, Barthel index (BI) score, FRAIL score, fall risk, pressure injury risk, feeding method, depression, age and dysphagia. CONCLUSION:The ML model identified higher NIHSS, BI, and FRAIL, family income, higher fall risk, pressure injury risk, older age, tube feeding, depression and dysphagia as the top 10 strongest risk predictors in identifying patients who required non-home discharge to higher levels of care. Modern ML techniques can support timely and appropriate clinical decision-making. RELEVANCE TO CLINICAL PRACTICE:This study illustrates the characteristics and risk factors of non-home discharge in patients with stroke, potentially contributing to the improvement of the discharge process. REPORTING METHOD:STROBE guidelines.

Introduction: Alopecia concerns more than half our adult population. Platelet-rich plasma (PRP) has been applied in skin rejuvenation and hair loss treatment. However, the pain and bleeding during injection and the troublesome for fresh preparation of each action limit PRP's in-depth applying dedication to clinics. Objectives: We report a temperature-sensitive PRP induced fibrin gel included in a detachable transdermal microneedle (MN) for hair growth. Results: PRP gel interpenetrated with the photocrosslinkable gelatin methacryloyl (GelMA) to realize sustained release of growth factors (GFs) and led to 14% growth in mechanical strength of a single microneedle whose strength reached 1.21 N which is sufficient to penetrate the stratum corneum. PRP-MNs' release of VEGF, PDGF, and TGF-b were characterized and quantitatively around the hair follicles (HFs) for 4-6 days consecutively. PRP-MNs promoted hair regrowth in mice models. From transcriptome sequencing, PRP-MNs induced hair regrowth through angiogenesis and proliferation. The mechanical and TGF-0 sensitive gene Ankrd1 was significantly upregulated by PRP-MNs treatment. Conclusion: PRP-MNs show convenient, minimally invasive, painless, inexpensive manufacture, storable and sustained effects in boosting hair regeneration.(c) 2023 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Dermal white adipose tissue (dWAT) is a dynamic component of the skin and closely interacts with the hair follicle. Interestingly, dWAT envelops the hair follicle during anagen and undergoes fluctuations in volume throughout the hair cycle. dWAT-derived extracellular vesicles can significantly regulate the hair cycle, and this provides a theoretical basis for utilizing adipose tissue as a feasible clinical strategy to treat hair loss. However, the amount and depth of the available literature are far from enough to fully elucidate the prominent role of dWAT in modulating the hair growth cycle. This review starts by investigating the hair cycle-coupled dWAT remodeling and the reciprocal signaling interplay underneath. Then, it summarizes the current literature and assesses the advantages and limitations of clinical research utilizing adipose-derived therapies for hair regeneration.

Norepinephrine (NE) is involved in auditory fear conditioning (AFC) in posttraumatic stress disorder (PTSD). However, it is still unclear how it acts on neurons. We aimed to investigate whether the activation of the β-adrenergic receptor (β-AR) improves AFC by sensitization of the prelimbic (PL) cortex at the animal, cellular, and molecular levels. In vivo single-cell electrophysiological recording was used to characterize the changes in neurons in the PL cortex after AFC. Then, PL neurons were locally administrated by the β-AR agonist isoproterenol (ISO), the GABAaR agonist muscimol, or intervened by optogenetic method, respectively. Western blotting and immunohistochemistry were finally used to assess molecular changes. Noise and low-frequency tones induced similar AFC. The expression of β-ARs in PL cortex neurons was upregulated after fear conditioning. Microinjection of muscimol into the PL cortex blocked the conformation of AFC, whereas ISO injection facilitated AFC. Moreover, PL neurons can be distinguished into two types, with type I but not type II neurons responding to conditioned sound and being regulated by β-ARs. Our results showed that β-ARs in the PL cortex regulate conditional fear learning by activating type I PL neurons.

ObjectiveThe research objective was to evaluate the predicting role of the vascular endothelial growth factor to CBP/P300-interacting transactivator with Glu/Asp-rich C-terminal domain 2 Ratio (VEGF/CITED2) from peripheral blood mononuclear cells (PBMCs) in the collateral circulation of acute ischemic stroke (AIS).MethodsIn an observational study of patients with AIS, the western blot was applied to test the protein expression of VEGF and CITED2. Then, we calculated the VEGF/CITED2 and collected other clinical data. Binary logistic regression analysis between collateral circulation and clinical data was performed. Finally, receiver operating characteristic (ROC) curve analysis was used to explore the predictive value of VEGF/CITED2.ResultsA total of 67 patients with AIS were included in the study. Binary logistic regression analysis indicated the VEGF/CITED2 (OR 165.79, 95%CI 7.25–3,791.54, P = 0.001) was an independent protective factor. The ROC analyses showed an area under the ROC curve of the VEGF/CITED2 was 0.861 (95%CI 0.761–0.961). The optimal cutoff value of 1.013 for VEGF/CITED2 had a sensitivity of 89.1% and a specificity of 85.7%.ConclusionIn patients with AIS, the VEGF/CITED2 was related to the establishment of collateral circulation. The VEGF/CITED2 is a potentially valuable biomarker for predicting collateral circulation.Clinical trial registrationClinicalTrials.gov, identifier: NCT05345366.

BACKGROUND AND AIM:Traumatic spinal cord injury (SCI) is a common and devastating central nervous disease, the treatment of which faces many challenges to the medical community and society as a whole. Treatment measures based on oxidative stress of spinal motor neurons during SCI are expected to help restore biological functions of neurons under injury conditions. However, to date, there are no systematic reports regarding oxidative stress on spinal motor neuron injury. Our aim is to better understand and explain the influences and mechanisms of oxidative stress on spinal motor neurons during SCI.METHODS:We first exposed VSC4.1 motor neurons to hydrogen peroxide (H2 O2 ) and evaluated the effects on cell viability, morphology, cycling, and apoptosis, with an emphasis on the changes to the cytoskeleton and the effect of N-acetyl-l-cysteine (NAC) on these changes. Then, we investigated the effects of NAC on these cytoskeletal changes in vitro and in vivo.RESULTS:We found that H2 O2 caused severe damage to the normal cytoskeleton, leading to a reduction in neurite length and number, rearrangement of the actin cytoskeleton, and disorder of the microtubules and neurofilaments in VSC4.1. Importantly, NAC attenuated the oxidative damage of spinal motor neurons in vitro and in vivo, promoting the recovery of hindlimb motor ability in mice with SCI at the early stage of injury.CONCLUSION:This study shows that oxidative stress plays an important role in the cytoskeleton destruction of spinal motor neurons in SCI, and treatment of SCI on this basis is a promising strategy. These findings will help to elucidate the role of oxidative stress in spinal motor neuron injury in SCI and provide references for further research into the study of the pathology and underlying mechanism of SCI.

Abstract Background: Evaluating the collateral circulation of acute ischemic stroke (AIS) mainly depends on the imaging examination. At present, there is no effective and sensitive biomarker for collateral circulation. Thus, the research objective was to evaluate the predicting role of the vascular endothelial growth factor to CBP/P300-interacting transactivator with Glu/Asp-rich C-terminal domain 2 Ratio (VEGF/CITED2) from peripheral blood mononuclear cells in the collateral circulation of AIS.Methods: A total of 67 patients with AIS were included in the study. We classified patients into two groups (the good collateral group and the poor collateral group) by DWI-ASPECTS score. The western blot was applied to test the protein expression of vascular endothelial growth factor (VEGF) and CBP/P300-interacting transactivator with Glu/Asp-rich C-terminal domain 2 (CITED2). Then, we calculated the VEGF/CITED2 and collected other clinical data. Binary logistic regression analysis between collateral circulation and clinical data was performed. Finally, Receiver operating characteristic (ROC) curve analysis was used to explore the predictive value of VEGF/CITED2.Results: There was a statistically significant difference in the white blood cell (WBC) count (P=0.036), neutrophil count (P=0.035), fibrinogen (Fib, P=0.038), homocysteine (Hcy, P=0.047), and VEGF/CITED2 (P=0.017) between the good collateral group and the poor collateral group. Moreover, WBC count (OR 0.77, 95%CI 0.63-0.95, P=0.016), neutrophil count (OR 0.78, 95%CI 0.63-0.95, P=0.016), NLR (OR 0.83, 95%CI 0.68-1.02, P=0.075), Hcy (OR 0.87, 95%CI 0.75-1.00, P=0.054), and Fib (OR 0.59, 95%CI 0.34-1.02, P=0.059) were the risk factors, and VEGF/CITED2 (OR 165.79, 95%CI 7.25-3791.54, P=0.001) was an independent protective factor. The ROC analyses showed an area under the ROC curve (AUC) of the VEGF/CITED2 was 0.861 (95%CI 0.761-0.961). The optimal cutoff value of 1.013 for VEGF/CITED2 had a sensitivity of 89.1% and a specificity of 85.7%.Conclusions: In patients with AIS, the VEGF/CITED2 was related to the establishment of collateral circulation. The VEGF/CITED2 is a potentially valuable biomarker for predicting collateral circulation.Trial registration: Clinical Trials. gov, NCT05345366, Registered on April 19, 2022, retrospectively registered.

Background: Osteosarcoma (OS) is the prevalent form of primary bone cancer among adolescents, but the 5-year overall survival rate for patients with a metastatic or recurrent OS is under 20%. Angio-associated migratory cell protein (AAMP) is known to be a key regulator of cellular migration, yet its role in the context of OS metastasis has yet to be firmly established. Methods: Bioinformatics analyses were used to explore the association between AAMP and YAP expression and the prognosis of OS patients, and to evaluate differences in AAMP expression in patients with primary OS, recurrent OS, and pulmonary metastatic OS. Immunohistochemical (IHC) staining was additionally performed to compare AAMP levels in primary OS and pulmonary metastatic OS patient samples. Lentiviral transduction was further used to establish OS cell lines in which AAMP or YAP had been stably knocked down or overexpressed. OS cell migration and invasion were assessed using wound healing and Transwell assays. Proteins associated with the mitochondria, the epithelial-mesenchymal transition (EMT), YAP, and its target proteins were assessed in OS cell lines via Western blotting. OS cell lamellipodia were detected via phalloidin staining. Mitochondrial morphological characteristics were assessed via transmission electron microscopy following the knockdown of AAMP. An ATP kit was employed to measure ATP levels in OS cells in which AAMP had been knocked down. Animal model studies were used to confirm indices associated with OS cell lung metastasis following AAMP knockdown. Results: Patients with metastatic OS exhibit higher levels of AAMP expression that are correlated with poorer patient prognosis. Knocking down AAMP suppressed the migratory, invasive, and EMT activity of analyzed OS cell lines. AAMP was found to regulate CFL1 and thereby control OS cell protrusion. AAMP knockdown was further found to promote OS cell mitochondrial dysfunction and decreased intracellular ATP production, with these AAMP knockdown cells exhibiting impaired migratory and invasive activity as a consequence of YAP inhibition. Consistently, the knockdown of AAMP suppressed the in vivo metastasis of OS cells. Conclusions: Together, these data highlight a model wherein AAMP can promote OS cell migratory and invasive activity by regulating YAP and mitochondrial functionality. The AAMP/CFL1/YAP signaling pathway may thus represent a viable therapeutic target for efforts aimed at suppressing the metastatic progression of OS.

PURPOSE:To evaluate the value of the NLR (neutrophil-to-lymphocyte ratio) and the fibrinogen level in predicting stroke-associated pneumonia (SAP) in acute ischemic stroke (AIS) patients.PATIENTS AND METHODS:In total, we enrolled 734 medical-ward patients with AIS in this retrospective study. Patients were divided into SAP (n=52) and non-SAP (n=682) groups according to the diagnostic criteria of SAP. Binary logistic regression analysis was used to analyze the relationship between the NLR, serum fibrinogen concentration and SAP. Receiver operating characteristic (ROC) curves were generated to identify the optimal cutoff points and assess the diagnostic value of the NLR, serum fibrinogen and the combination of NLR and fibrinogen in predicting SAP.RESULTS:SAP occurred in 52 (7.08%) patients among the enrolled AIS patients. Binary logistic regression analysis showed that the NLR (odds ratio [OR]: 2.802, 95% confidence interval [CI]: 1.302-6.032, P=0.008) and serum fibrinogen concentration (OR: 7.850, 95% CI: 3.636-16.949, P=0.000) were independently associated with a higher risk of SAP incidence after adjusting for age, sex, ASPECT score, atrial fibrillation, nasogastric tube feeding, LDL-C and TC, temperature at admission and mechanical ventilation. The optimal cutoff points of the NLR and serum fibrinogen to distinguish SAP among AIS patients were 3.603 (AUC, 0.690; NPV, 95.78; PPV, 19.01) and 4.595 (AUC, 0.727; NPV, 95.60; PPV, 24.49), respectively. When the combination of NLR and fibrinogen was used to predict SAP, the optimal cutoff points were >2.436 for NLR and >3.24 for fibrinogen (AUC, 0.758; NPV, 98.50; PPV, 11.80).CONCLUSION:The NLR and serum fibrinogen might have greater negative diagnostic value in predicting SAP among AIS patients. Combining the NLR and serum fibrinogen showed an increased AUC for predicting SAP among AIS patients.

Aims: Usually glial scar that occurs after central nervous system injury has significantly affected the local neural microenvironment. Meningeal fibroblasts play an essential role in the formation of the glial scar. However, how and why meningeal fibroblasts migrate to lesion sites is still unclear. Main methods: Astrocytes were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) injury. And then, we measured the glial fibrillary acidic protein(GFAP) and chondroitin sulfate proteoglycans (CSPGs) expression of reactive astrocytes by western blot and quantitative polymerase chain reaction (qPCR) after they were cocultured with meningeal fibroblasts. Following, we clarified the possibility that CSPGs induce the migration of meningeal fibroblasts to glial scar by transwell migration assay and the activation of the p38 MAPK signaling pathway during the migration by western blot. Key findings: We found that co-cultured meningeal fibroblasts could alleviate the significantly increased expression of GFAP and CSPGs in the activation of reactive astrocytes induced by OGD/R. Additionally, CSPGs secreted by reactive astrocytes could induce the migration of meningeal fibroblasts and the expression of phospho-p38 in meningeal fibroblasts when meningeal fibroblasts were co-cultured with supernatant of reactive astrocytes. What's more, we could observe a noticeable increase in CSPGs that chondroitinase ABC could reverse their functions. Moreover, phospho-p38 could cause the expression of phospho-cofilin and the migration of CSPGs-induced meningeal fibroblasts. Significance: Our study provides reliable evidence for explaining scar formation mechanisms and further studying to improve regeneration after an injury to the central nervous system.

Introduction: Regenerative medicine is a promising approach for hair loss; however, its primary challenge is the inductivity of human dermal papilla cells (DPCs), which rapidly lose hair growth-inducing properties in 2D culture. Despite extensive research efforts to construct DPCs, current 3D microenvironments fabricated to restore hair inductivity remain insufficient. Objectives: Here, we aimed to fabricate ECM-enriched controllable vascularized dermal papilla (DP) spheroids that highly mimic in vivo DPCs microenvironments to restore their hair inductivity. Methods: We employed layer-by-layer (LbL) self-assembly using gelatin and alginate to construct nanoscale biomimetic ECM for DPCs, with Ca2+ as a cross-linking agent to create controllable DP spheroids. DPCs were also co-cultured with human umbilical vein endothelial cells to construct vascularized DP spheroids. Immunofluorescence staining and angiography was used to detect angiogenesis in vitro and in vivo. RNA sequencing and in vivo implantation were employed to investigate DPCs signature. Results: LbL technology enabled DPCs to aggregate into controllable DP spheroids of size and cell numbers similar to those of primary DP. Vascularization prevented hypoxia-induced necrosis and functioned in association with host vessels post-transplantation. Compared with traditional 3D culture, nanoscale ECM and vascularization were found to restore the transcriptional signature of DPCs and triple hair induction efficiency following engraftment. Conclusion: Our novel biomimetic developmental tissue engineering strategy is a crucial step toward the recovery of human DPC hair inductivity, which would enable the rapid clinical application of large-scale hair regeneration platforms.

Background: Spasticity is a common sequela of stroke. The incidence of poststroke spasticity (PSS) has not been systematically reviewed in recent years, and some risk factors remain debated. This systematic review and meta-analysis was conducted to determine the prevalence and risk factors for PSS. Methods: We searched electronic databases (PubMed, Embase, Cochrane Library, CNKI, WANFANG and CBM) inception to May 12, 2020. Observational studies summarizing the incidence or risk factors for PSS were included. Only cohort studies were enrolled in meta-analysis. For risk factors examined in at least three different studies, we combined effects into odds ratios (OR) and 95% confidence intervals (CI). Results: One thousand four hundred sixty-seven studies were retrieved and 23 were involved in meta-analysis. The pooled prevalence of spasticity after stroke was 25.3% and that after the first-ever stroke was 26.7%. The incidence of spasticity after the first-ever stroke with paresis was 39.5%. The prevalence of disabling or severe spasticity (MAS ≥ 3) in stroke patients with paresis was 9.4% (95% CI 0.056–0.133), and severe spasticity was 10.3% (95% CI 0.058–0.149). Moderate to severe paresis (OR = 6.573, 95% CI 2.579–16.755, I 2 = 0.0%), hemorrhagic stroke (OR = 1.879, 95% CI 1.418–2.490, I 2 = 27.3%) and sensory disorder were risk factors for PSS. Conclusions: The incidence of PSS was significantly higher in stroke patients with paresis. Patients with moderate to severe paresis and sensory disorder should be closely followed up. The role of hemorrhagic stroke in predicting PSS remains to be further explored.

Approximately 89% of patients with Parkinson's disease (PD) suffer from dysarthria. Lee Silverman Voice Treatment (LSVT), a behavioral therapy, aims to improve speech and voice functions. The objective was to assess the effectiveness of LSVT compared with other/no speech interventions for dysarthria in patients with PD. Electronic databases, including PubMed, Embase and the Cochrane Library, were searched. The publication date of all included studies was before 6 March 2020. Only randomized controlled trials (RCTs) that evaluated the LSVT intervention compared with other/no speech intervention were considered. The data obtained from the included studies were described and the mean differences were calculated. Eight RCTs were included in this meta-analysis comparing LSVT with other/no speech interventions. In the comparison of LSVT versus no intervention, vocal intensity for sustained 'Ah' phonation, reading the 'Rainbow passage', monologue and describing a picture increased by 8.87, 4.34, 3.25 and 3.31 dB, respectively, after 1 month of therapy. Compared with the respiratory therapy group, the LSVT group also showed significant improvement in vocal intensity for sustained 'Ah' phonation, reading the 'Rainbow passage' and monologue immediately after treatment (13.39, 6.66 and 3.19 dB). Positive improvement still existed after 24 months. There was no difference in the therapeutic effect between face-to-face and online LSVT. The effectiveness of LSVT for dysarthria in patients with PD was verified in these trials. However, future RCTs with sufficient participants are essential to evaluate the effectiveness of LSVT for dysarthria.

Inducing somatic cells into neural stem cells (iNSCs) in specific ways provides a new cell therapy in a variety of neurological diseases. In the past, iNSCs were generated by transcription factors which increased the risk of mutagenesis, tumor formations, and immune reactions by viral transduction vectors. Therefore, in this study, different small molecules were used to induce mouse embryonic fibroblasts (MEFs) into iNSCs in different reprogramming stages, which showed high reprogramming efficiency without altering the genome. We demonstrated that the small molecules staged-induction neural stem cells (SMSINS) have the characteristics of neural stem cells (NSCs) in morphology, gene expression, self-renewal and differentiation potential. Furthermore, valproic acid (VPA), one of small molecules, was showed to enhance neural induction with highest efficiency compared with six other small molecules, which were also investigated in the present study. Moreover, our results suggested that activating the mammalian target of rapamycin (mTOR) signaling enhanced the induction efficiency and neuronal differentiation. Collectively, our findings indicated that using this induction program allowed us to obtain safe and efficient iNSCs which were free of genetic manipulation. The VPA-mediated mTOR signaling pathway may enhance reprogramming efficiency and neuronal differentiation. So we suggested that this program could be a new method of obtaining iNSCs for the treatment of neurological diseases by cell replacement therapy in the future.

Traumatic brain injury (TBI) is to date one of the major critical conditions causing death and disability worldwide. Exogenous neural stem/precursor cells (NSCs/NPCs) hold great promise for improving neurological dysfunction, but their functional properties in vivo remain unknown. Human neural precursor cells (hNPCs) carrying one fluorescent reporter gene (DsRed) can be observed directly in vivo using two-photon laser-scanning microscope. Therefore, we evaluated the neural integration and potential therapeutic effect of hNPCs on mice with TBI. Behavioral tests were performed by rotarod task and Morris Water Maze task. Neural integration was detected by fluorometric Ca2+ imaging and nerve tracing. We found that motor and cognition functions were significantly improved in mice with hNPCs injection compared to mice with vehicle treatment, and hNPCs integrated into the host circuit and differentiated toward neuronal lineage. Our study provided reliable evidence for further hNPCs transplantation in clinical practice.

The present study aimed to explore the effects of n-3 polyunsaturated fatty acids (PUFAs) on autophagy and their potential for promoting locomotor recovery after spinal cord injury (SCI). Primary neurons were isolated and cultured. Sprague-Dawley rats were randomly divided into three groups and fed diets with different amounts of n-3 PUFAs. A model of spinal cord contusion was created at the T10 spinal segment and the composition of PUFAs was analyzed using gas chromatography. Spinal repair and motor function were evaluated postoperatively. Assessment of the effects of n-3 PUFAs on autophagy and mammalian target of rapamycin complex 1 (mTORC1) was performed using immunofluorescence staining and western blotting. In vitro, n-3 PUFAs inhibited mTORC1 and enhanced autophagy. The n-3 PUFA levels and the ratio of n-3 PUFA to n-6 PUFA in the spinal cord and serum of rats fed a high-n-3 PUFA diet were higher before and after operation (P<0.05). Additionally, rats in the high-n-3 PUFA group showed improved motor function recovery, spinal cord repair-related protein expression level (MBP, Galc and GFAP). Expression levels if these protiens in the high-n-3 PUFA diet group expressed the highest levels, followed by the low-n-3 PUFA diet group and finally the control group (P<0.05). high-n-3 PUFA diet promoted autophagy ability and inhibited activity of the mTORC1 signaling pathway compared with the low-n-3 PUFA diet group or the control group (P<0.05). These results suggest that exogenous dietary n-3 PUFAs can inhibit mTORC1 signaling and enhance autophagy, promoting functional recovery of rats with SCI.

The narrow therapeutic time window and risk of intracranial hemorrhage largely restrict the clinical application of thrombolysis in acute ischemic stroke. Adjunctive treatments added to rt-PA may be beneficial to improve the capacity of neural cell to withstand ischemia, and to reduce the hemorrhage risk as well. This review aims to evaluate the neuroprotective effects of adjunctive treatments in combination with thrombolytic therapy for acute ischemic stroke. Relevant studies were searched in the PubMed, Web of Science and EMBASE database. In this review, we first interpret the potential role of adjunctive treatments to thrombolytic therapy in acute ischemic stroke. Furthermore, we summarize the current clinical evidence for the combination of intravenous recombinant tissue plasminogen activator and various adjunctive therapies in acute ischemic stroke, either pharmacological or non-pharmacological therapy, and discuss the mechanisms of some promising treatments, including uric acid, fingolimod, minocycline, remote ischemic conditioning, hypothermia and transcranial laser therapy. Even though fingolimod, minocycline, hypothermia and remote ischemic conditioning have yielded promising results, they still need to be rigorously investigated in further clinical trials. Further trials should also focus on neuroprotective approach with pleiotropic effects or combined agents with multiple protective mechanisms.

Osteoporosis (OP) increases the risk of bone fractures and other complications, and is thus a major clinical problem. In this study, we examined the effect of isopsoralen on the differentiation of bone-derived marrow mesenchymal stem cells (BMSCs) into osteoblasts and adipocytes, as well as bone formation under osteoporotic conditions. Primary femoral BMSCs isolated from C57BL/6 mice were used to evaluate the isopsoralen-mediated regulation of the expression of alkaline phosphatase (ALP), osteocalcin (OCN) and runt-related transcription factor 2 (RUNX2) during osteogenesis 2 weeks. We also examined the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein β (C/EBPβ) under adipogenic conditions for 1 and 2 weeks. In addition, ovariectomized (OVX) mice were used to examine the effects of isopsoralen on bone formation for 2 months. Finally, mammalian target of rapamycin complex 1 (mTORC1) signaling was examined under osteogenic and adipogenic conditions. We found that following treatment with isopsoralen, the expression levels of ALP, OCN and RUNX2 were upregulated, whereas those of PPARγ and C/EBPβ were downregulated. mTORC1 signaling was also inhibited in vitro and in vivo. In the OVX mice that were intragastrically administered isopsoralen, bone parameters (trabecular thickness, bone volume/total volume and trabecular number) in the distal femoral metaphysis were significantly increased and the adipocyte number was decreased. On the whole, our findings demonstrate that isopsoralen promoted BMSC differentiation into osteoblasts and suppressed differentiation into adipocytes.