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.

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.

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.