Combined application of neural stem/progenitor cells and scaffolds on locomotion recovery following spinal cord injury in rodents: a systematic review and meta-analysis.

BACKGROUND: This present study evaluates the pre-clinical evidence on the efficacy of NS/PC and scaffold (NS/PC + scaffold) transplantation on locomotor recovery after traumatic spinal cord injury (SCI). METHOD: Two independent reviewers screened the records gathered through a systematic search in MEDLINE, Embase, Scopus, and Web of Sciences databases. Studies on rats/mice evaluating the efficacy of simultaneous transplantation of NS/PCs and scaffold in the treatment of SCI were included. The results were reported as standardized mean difference (SMD) and 95% confidence interval (95% CI). RESULTS: Forty-seven articles were retrieved. Analyses showed that NS/PC + scaffold transplantation significantly improved locomotion in animals with SCI compared to that of the non-treatment group (SMD = 2.71, 95% CI: 1.89 to 3.54; I2 = 95.15%, p < 0.0001), scaffold alone (SMD = 2.28; 95% CI: 1.56 to 3.00; I2 = 94.38%; p < 0.0001), and NS/PCs alone (SMD = 1.74, 95% CI: 0.64 to 2.83; I2 = 92.02%, p < 0.0001). Moreover, the effectiveness of the treatment significantly increases when PLGA-based scaffolds and antibiotics are used. In addition, the NS/PC + scaffold transplantation during the first week after injury led to a significant improvement in locomotion, while concomitant transplantation of NS/PC + scaffold did not improve locomotion in cervical lesions. CONCLUSION: The findings showed that using NS/PCs with scaffold not only improves locomotion recovery, but also is superior to NS/PCs alone and scaffold alone. Future experiments and translational clinical studies are recommended to focus on the assessment of the safety and efficacy of the application of NS/PC + scaffold on SCI recovery.

Lavender protects H9c2 cardiomyocytes against oxygen-glucose deprivation (OGD)-induced injury via targeting the JAK2/STAT3 pathway.

Objectives: This study was conducted to examine the therapeutic effects of lavender oil (LO) against oxygen-glucose deprivation (OGD)-induced injury in vitro model. Materials and Methods: In this study, the OGD model was induced in the H9C2 cell line, and then the cells were treated with LO (10, 100, 1000, and 10000 µg/ml). The anti-inflammatory activity of LO (JAK2/STAT3) was evaluated by immunocytochemical assay. Likewise, the p-ERK/ERK level was measured by western blotting. Results: Compared with only the OGD-induced injury model, cell survival increased after treatment with LO. Our results showed that 100 µg/ml of LO significantly decreased the expression of Jak2/Stat3 and the apoptotic activity 72 hr after reperfusion compared with the control group. Likewise, significant increases were observed in p-ERK/ERK in LO-treated groups. Conclusion: Collectively, these findings confirm that LO can be a good candidate to reduce OGD-induced injury in the H9C2 cell line through targeting Jak2/Stat3 and ERK pathways.

The efficacy of GABAergic precursor cells transplantation in alleviating neuropathic pain in animal models: a systematic review and meta-analysis.

BACKGROUND: Current therapies are quite unsuccessful in the management of neuropathic pain. Therefore, considering the inhibitory characteristics of GABA mediators, the present systematic review and meta-analysis aimed to determine the efficacy of GABAergic neural precursor cells on neuropathic pain management. METHODS: Search was conducted on Medline, Embase, Scopus, and Web of Science databases. A search strategy was designed based on the keywords related to GABAergic cells combined with neuropathic pain. The outcomes were allodynia and hyperalgesia. The results were reported as a pooled standardized mean difference (SMD) with a 95% confidence interval (95% CI). RESULTS: Data of 13 studies were analyzed in the present meta-analysis. The results showed that administration of GABAergic cells improved allodynia (SMD = 1.79; 95% CI: 0.87, 271; P < 0.001) and hyperalgesia (SMD = 1.29; 95% CI: 0.26, 2.32; P = 0.019). Moreover, the analyses demonstrated that the efficacy of GABAergic cells in the management of allodynia and hyperalgesia is only observed in rats. Also, only genetically modified cells are effective in improving both of allodynia, and hyperalgesia. CONCLUSIONS: A moderate level of pre-clinical evidence showed that transplantation of genetically-modified GABAergic cells is effective in the management of neuropathic pain. However, it seems that the transplantation efficacy of these cells is only statistically significant in improving pain symptoms in rats. Hence, caution should be exercised regarding the generalizability and the translation of the findings from rats and mice studies to large animal studies and clinical trials.

Investigating the in vitro photothermal effect of green synthesized apigenin-coated gold nanoparticle on colorectal carcinoma.

Applying toxic chemical to the synthesis of stable gold nanoparticles is one of the limitations of gold nanoparticles for therapeutic applications such as photothermal therapy. Plant compounds such as apigenin (API) with therapeutic potential can be applied in the synthesis of gold nanoparticles. API-coated gold nanoparticles (Api@AuNPs) with an average size of 19.1 nm and a surface charge of -4.3 mV have been synthesized by a simple and efficient technique. The stability of Api@AuNPs in the biological environment was verified through UV-Vis spectroscopy. Based on Raman and FTIR spectroscopy analysis, chemical binding of API on the surface of Api@AuNPs through hydroxyl and carbonyl functional groups was found to be the main reason for the stability of the Api@AuNPs in comparison with citrate-coated gold nanoparticles (Cit@AuNPs). The synthesized Api@AuNPs do not cause major toxic effects up to 128 ppm. Api@AuNP-mediated photothermal therapy leads to the indiscriminate eradication of almost half of both mouse fibroblastic (L929) and colorectal cancer (CT26) cells. Flow-cytometry analysis revealed that the cell death mechanism is mainly apoptosis. In the apoptosis triggered cell death in photothermal treatment, Api@AuNPs are preferred over commonly used gold nanoparticles in photothermal treatments which mostly trigger the necrosis cell death pathway.

Value of Canadian C-spine rule versus the NEXUS criteria in ruling out clinically important cervical spine injuries: derivation of modified Canadian C-spine rule.

PURPOSE: Although, Canadian C-spine rule and the National Emergency X-Radiography Utilization Study (NEXUS) criteria in ruling out clinically important cervical spine injuries have been validated using large prospective studies, no consensus exist as to which rule should be endorsed. Therefore, the aim of the present study was to compare the accuracy of the Canadian C-spine and NEXUS criteria in ruling out clinically important cervical spine injuries in trauma patients. Finally, we introduced the modified Canadian C-spine rule. METHODS: A prospective diagnostic accuracy study was conducted on trauma patients referred to four emergency departments of Iran in 2018. Emergency physicians evaluated the patients based on the Canadian C-spine rule and NEXUS criteria in two groups of low risk and high risk for clinically important cervical spine injury. Afterward, all patients underwent cervical imaging. In addition, modified Canadian C-spine rule was derived by removing dangerous mechanism and simple rear-end motor vehicle collision from the model. RESULTS: Data from 673 patients were included. The area under the curve of the NEXUS criteria, Canadian C-spine, and modified Canadian C-spine rule were 0.76 [95% confidence interval (CI) 0.71-0.81)], 0.78 (95% CI 0.74-0.83), and 0.79 (95% CI 0.74-0.83), respectively. The sensitivities of NEXUS criteria, Canadian C-spine, and modified Canadian C-spine rule were 93.4%, 100.0% and 100.0%, respectively. CONCLUSIONS: The modified Canadian C-spine rule has fewer variables than the original Canadian C-spine rule and is entirely based on physical examination, which seems easier to use in emergency departments.

Nanomaterial integration into the scaffolding materials for nerve tissue engineering: a review.

The nervous system, which consists of a complex network of millions of neurons, is one of the most highly intricate systems in the body. This complex network is responsible for the physiological and cognitive functions of the human body. Following injuries or degenerative diseases, damage to the nervous system is overwhelming because of its complexity and its limited regeneration capacity. However, neural tissue engineering currently has some capacities for repairing nerve deficits and promoting neural regeneration, with more developments in the future. Nevertheless, controlling the guidance of stem cell proliferation and differentiation is a challenging step towards this goal. Nanomaterials have the potential for the guidance of the stem cells towards the neural lineage which can overcome the pitfalls of the classical methods since they provide a unique microenvironment that facilitates cell-matrix and cell-cell interaction, and they can manipulate the cell signaling mechanisms to control stem cells' fate. In this article, the suitable cell sources and microenvironment cues for neuronal tissue engineering were examined. Afterward, the nanomaterials that impact stem cell proliferation and differentiation towards neuronal lineage were reviewed.

The Efficacy of Ketamine Administration in Prehospital Pain Management of Trauma Patients; a Systematic Review and Meta-Analysis.

INTRODUCTION: Although previous articles and reviews suggest that ketamine might effectively manage pain in trauma patients, these articles have serious limitations. Accordingly, the current meta-analysis aims to investigate the efficacy of ketamine administration in prehospital pain management of trauma patients. METHOD: In the present meta-analysis, controlled human studies were included. An extensive search was conducted in electronic databases including Medline (via PubMed), Embase, Central, Scopus, Web of Science, and ProQuest, gathering data to the end of 2018. The efficacy and side effects of ketamine administration in pre-hospital pain management were compared with those of opioid analgesics based on standard mean difference (SMD) and odds ratio (OR) calculations with 95% confidence interval (95% CI). RESULTS: Data from seven articles were included in the present meta-analysis. Ketamine administration was not more effective than administrating morphine or fentanyl in prehospital pain management of trauma patients (SMD = -0.56, 95% CI: -1.38 to 0.26, p = 0.117). However, co-administration of ketamine+morphine was considerably more effective than ketamine alone, in alleviating pain in prehospital settings (SMD = -0.62, 95% CI: -1.12 to -0.12, p = 0.010). Finally, it was concluded that ketamine alone had less side effects than morphine alone (OR = 0.25, 95% CI: 0.11 to 0.56, p = 0.001). However, co-administration of ketamine+morphine increases the risk of side effects to 3.68 times compared to when morphine is prescribed solely (OR=3.68, 95% CI: 1.99 to 6.82, p<0.001). CONCLUSION: For the first time, findings of the current meta-analysis demonstrated that ketamine, being administered alone, is an effective and safe medication in prehospital pain management in trauma patients, and can be considered as an acceptable alternative to opioid analgesics.

Pre-hospital pain management; a systematic review of proposed guidelines.

INTRODUCTION: A standard guideline concerning pre-hospital pain management is still a matter of discussion. Therefore, the current umbrella review is determined to perform a comprehensive search in databases and Grey literature and collect and summarize the guidelines and protocols dealing with prehospital pain management. METHODS: In the present study, all of the available guidelines and protocols concerning pre-hospital pain management were reviewed. Presented guidelines are from 2010 up to present, as the majority of guidelines are considered old and become renewed after 10 years. Finally, the development quality of each guideline was evaluated using AGREE II instrument. RESULTS: The search conducted in databases and non-indexed protocols resulted in inclusion of 12 pre-hospital pain management guidelines. The time interval of the guidelines was from 2010 to 2019. Four guidelines were designed for pain management in trauma patients and other guidelines were presented for all of the clinical conditions associated with pain. All of the 12 included guidelines presented pain management instructions in adults. Pain management in children was reported in 10 guidelines. All of the guidelines persisted on a standard method for pain evaluation. Pain management was categorized in three groups; mild, moderate and severe pain. Most of the guidelines recommend paracetamol as an optional treatment for management of mild pain in both adults and children. In management of moderate and severe pain, fentanyl and morphine were suggested for both adults and children. In most of the treatment guidelines fentanyl is the optional choice for children. CONCLUSION: The present umbrella review has summarized the current evidence in pre-hospital pain management for the first time via investigation of guidelines and protocols related to the matter. Based on the obtained evidence, no guideline is yet presented concerning opioid-free management of moderate and severe pain. The evidence is insufficient for using non opioid medications such as ketamine.

A combination of mesenchymal stem cells and scaffolds promotes motor functional recovery in spinal cord injury: a systematic review and meta-analysis.

OBJECTIVE: There is controversy about the role of scaffolds as an adjunctive therapy to mesenchymal stem cell (MSC) transplantation in spinal cord injury (SCI). Thus, the authors aimed to design a meta-analysis on preclinical evidence to evaluate the effectiveness of combination therapy of scaffold + MSC transplantation in comparison with scaffolds alone and MSCs alone in improving motor dysfunction in SCI. METHODS: Electronic databases including Medline, Embase, Scopus, and Web of Science were searched from inception until the end of August 2018. Two independent reviewers screened related experimental studies. Animal studies that evaluated the effectiveness of scaffolds and/or MSCs on motor function recovery following experimental SCI were included. The findings were reported as standardized mean difference (SMD) and 95% confidence interval (CI). RESULTS: A total of 34 articles were included in the meta-analysis. Analyses show that combination therapy in comparison with the scaffold group alone (SMD 2.00, 95% CI 1.53-2.46, p < 0.0001), the MSCs alone (SMD 1.58, 95% CI 0.84-2.31, p < 0.0001), and the nontreated group (SMD 3.52, 95% CI 2.84-4.20, p < 0.0001) significantly improved motor function recovery. Co-administration of MSCs + scaffolds only in the acute phase of injury (during the first 3 days after injury) leads to a significant recovery compared to scaffold alone (SMD 2.18, p < 0.0001). In addition, the cotransplantation of scaffolds with bone marrow-derived MSCs (SMD 1.99, p < 0.0001) and umbilical cord-derived MSCs (SMD 1.50, p = 0.001) also improved motor function following SCI. CONCLUSIONS: The findings showed that scaffolds + MSCs is more effective than scaffolds and MSCs alone in improving motor function following SCI in animal models, when used in the acute phase of injury.

Co-expression of TLR-9 and MMP-13 is associated with the degree of tumour differentiation in prostate cancer.

In vitro experiments demonstrated that stimulation of Toll-like receptor 9 (TLR-9) by synthetic TLR-9 ligands induces the invasion of TLR-9-expressing prostate cancer cells through matrix metalloproteinase 13 (MMP-13). However, the clinical value of TLR-9 and MMP-13 co-expression in the pathophysiology of the prostate is unknown. In the study, we evaluated the expression levels and clinical significance of the TLR-9 and MMP-13 in a series of prostate tissues. One hundred and eighty prostate tissues including prostate cancer (PCa) (n = 137), high-grade prostatic intraepithelial neoplasia (HPIN) (n = 18) and benign prostatic hyperplasia (BPH) (n = 25) were immunostained for the TLR-9 and MMP-13 markers. Subsequently, the correlation between the TLR-9 and MMP-13 staining scores and clinicopathological parameters was obtained. Higher expressions of TLR-9 and MMP-13 were found in PCa and high-grade prostatic intraepithelial neoplasia compared to benign prostatic hyperplasia tissues. Among PCa samples, a positive relationship was revealed between the MMP-13 expression and Gleason score (P < 0.001). There was a significant correlation between TLR-9 expression and regional lymph node involvement (P = 0.04). The expression patterns of TLR-9 and MMP-13 markers demonstrated a reciprocal significant correlation between the two markers in the same series of prostate samples (P < 0.001). Furthermore, the Gleason score of TLR-9high /MMP-13high and TLR-9low /MMP-13low phenotypes showed a significant difference (P = 0.002). Higher expressions of TLR-9 and MMP-13 can confer aggressive behaviour to PCa. Therefore, these markers may be used as a valuable target for tailored therapy of PCa.

Gene Silencing of TGFßRII Can Inhibit Glioblastoma Cell Growth

Objective: Glioblastoma (GBM) is the most malignant and aggressive type of glioma, associated with a high rate of mortality. The transforming growth factor-ß receptor II (TGFß RII) is involved in glioma initiation and progression. On the other hand, TGFß RII silencing is critical to the inhibition of GBM. Therefore, we aimed to determine the effects of specific TGFß RII siRNA on the survival of U-373MG cells. Methods: TGFß RII siRNA was transfected, and qRT-PCR was performed to examine TGFß RII mRNA expression. Cell survival was determined using colorimetric MTT assay, and platelet-derived growth factor-BB (PDGF-BB) level was measured in the culture supernatant using ELISA assay. Result: Our findings indicated that specific siRNAs could dose-dependently suppress TGFß RII mRNA expression after 48 hours. In addition, treatment with TGFß RII siRNA significantly reduced tumor cell survival and decreased the amount of PDGF-BB protein in the cell culture supernatant. Conclusion: Our results suggest that TGFß RII silencing can be a promising complementary treatment for glioma.