sj-tif-1-cll-10.1177_09636897231210069 – Supplemental material for Human Umbilical Cord Mesenchymal Stem Cells Improve the Status of Hypoxic/Ischemic Cerebral Palsy Rats by Downregulating NogoA/NgR/Rho Pathway

Supplemental material, sj-tif-1-cll-10.1177_09636897231210069 for Human Umbilical Cord Mesenchymal Stem Cells Improve the Status of Hypoxic/Ischemic Cerebral Palsy Rats by Downregulating NogoA/NgR/Rho Pathway by Yaoling Luo, Jiayang Qu, Zhengyi He, Minhong Zhang, Zhengwei Zou, Lincai Li, Yuxian Zhang and Junsong Ye in Cell Transplantation</p

DataSheet_1_Gracillin Shows Potential Efficacy Against Non-Small Cell Lung Cancer Through Inhibiting the mTOR Pathway.docx

The leading cause of cancer deaths is lung cancer, non-small cell lung cancer (NSCLC), the most common type of lung cancers, remains a difficult cancer to treat and cure. It is urgent to develop new products to treat NSCLS. Gracillin, extracted from Reineckia carnea, Dioscorea villosa, and other medicinal plants, has anti-tumor potential with toxic effect on a variety of tumor cells such as NSCLC. However, the anti-NSCLC mechanism of gracillin is not completely clear. In this study, A549 cells and athymic nude mice were used as models to evaluate the anti-NSCLC effects of gracillin. The antiproliferative activity of gracillin on A549 cells was conducted by CCK-8, and obvious autophagy was observed in gracillin-treated A549 through transmission electron microscopy. Furthermore, the expressions of Beclin-1, LC3-II, and WIPI1 were upregulated, while the expression of p62 was downregulated in gracillin-treated A549. The further mechanism study found that the mTOR signaling pathway was significantly inhibited by gracillin. Accordingly, the PI3K/Akt pathway positively regulating mTOR was inhibited, and AMPK negatively regulating mTOR was activated. Meanwhile, LC3-II transformation was found to be significantly reduced after WIPI1 was silenced in A549 cells but increased after gracillin treatment. It also proves that WIPI is involved in the process of gracillin regulating A549 autophagy. At last, the anti-tumor growth activity of gracillin in vivo was validated in A549-bearing athymic nude mice. In conclusion, gracillin has anti-NSCLC activity by inducing autophagy. The mechanism maybe that gracillin inhibited the mTOR signaling pathway. Gracillin has the potential to be a candidate product for the treatment of NSCLC in the future.</p

Presentation_1_Efficacy and Safety of Stem Cell Therapy in Children With Autism Spectrum Disorders: A Systematic Review and Meta-Analysis.PDF

AimThere is insufficient evidence regarding the efficacy and safety of stem cell therapy for autism spectrum disorders. We performed the first meta-analysis of stem cell therapy for autism spectrum disorders in children to provide evidence for clinical rehabilitation.MethodsThe data source includes PubMed/Medline, Web of Science, EMBASE, Cochrane Library and China Academic Journal, from inception to 24th JULY 2021. After sifting through the literature, the Cochrane tool was applied to assess the risk of bias. Finally, we extracted data from these studies and calculated pooled efficacy and safety.Results5 studies that met the inclusion criteria were included in current analysis. Meta-analysis was performed using rehabilitation therapy as the reference standard. Data showed that the Childhood Autism Rating Scale score of stem cell group was striking lower than the control group (WMD: −5.96; 95%CI [−8.87, −3.06]; p ConclusionsThe results of this meta-analysis suggested that stem cell therapy for children with autism might be safe and effective. However, the evidence was compromised by the limitations in current study size, lacking standardized injection routes and doses of stem cells, as well as shortages in diagnostic tools and long period follow-up studies. Hence, it calls for more studies to systematically confirm the efficacy and safety of stem cell therapy for children with autism spectrum disorders.</p

Image1_Efficacy and safety of stem cell therapy in cerebral palsy: A systematic review and meta-analysis.TIF

Aim: Although the efficacy and safety of stem cell therapy for cerebral palsy has been demonstrated in previous studies, the number of studies is limited and the treatment protocols of these studies lack consistency. Therefore, we included all relevant studies to date to explore factors that might influence the effectiveness of treatment based on the determination of safety and efficacy.Methods: The data source includes PubMed/Medline, Web of Science, EMBASE, Cochrane Library, from inception to 2 January 2022. Literature was screened according to the PICOS principle, followed by literature quality evaluation to assess the risk of bias. Finally, the outcome indicators of each study were extracted for combined analysis.Results: 9 studies were included in the current analysis. The results of the pooled analysis showed that the improvements in both primary and secondary indicators except for Bayley Scales of Infant and Toddler Development were more skewed towards stem cell therapy than the control group. In the subgroup analysis, the results showed that stem cell therapy significantly increased Gross Motor Function Measure (GMFM) scores of 3, 6, and 12 months. Besides, improvements in GMFM scores were more skewed toward umbilical cord mesenchymal stem cells, low dose, and intrathecal injection. Importantly, there was no significant difference in the adverse events (RR = 1.13; 95% CI = [0.90, 1.42]) between the stem cell group and the control group.Conclusion: The results suggested that stem cell therapy for cerebral palsy was safe and effective. Although the subgroup analysis results presented guiding significance in the selection of clinical protocols for stem cell therapy, high-quality RCTs validations are still needed.</p

Table2_Efficacy and safety of stem cell therapy in cerebral palsy: A systematic review and meta-analysis.XLS

Aim: Although the efficacy and safety of stem cell therapy for cerebral palsy has been demonstrated in previous studies, the number of studies is limited and the treatment protocols of these studies lack consistency. Therefore, we included all relevant studies to date to explore factors that might influence the effectiveness of treatment based on the determination of safety and efficacy.Methods: The data source includes PubMed/Medline, Web of Science, EMBASE, Cochrane Library, from inception to 2 January 2022. Literature was screened according to the PICOS principle, followed by literature quality evaluation to assess the risk of bias. Finally, the outcome indicators of each study were extracted for combined analysis.Results: 9 studies were included in the current analysis. The results of the pooled analysis showed that the improvements in both primary and secondary indicators except for Bayley Scales of Infant and Toddler Development were more skewed towards stem cell therapy than the control group. In the subgroup analysis, the results showed that stem cell therapy significantly increased Gross Motor Function Measure (GMFM) scores of 3, 6, and 12 months. Besides, improvements in GMFM scores were more skewed toward umbilical cord mesenchymal stem cells, low dose, and intrathecal injection. Importantly, there was no significant difference in the adverse events (RR = 1.13; 95% CI = [0.90, 1.42]) between the stem cell group and the control group.Conclusion: The results suggested that stem cell therapy for cerebral palsy was safe and effective. Although the subgroup analysis results presented guiding significance in the selection of clinical protocols for stem cell therapy, high-quality RCTs validations are still needed.</p

Table1_Efficacy and safety of stem cell therapy in cerebral palsy: A systematic review and meta-analysis.DOCX

Aim: Although the efficacy and safety of stem cell therapy for cerebral palsy has been demonstrated in previous studies, the number of studies is limited and the treatment protocols of these studies lack consistency. Therefore, we included all relevant studies to date to explore factors that might influence the effectiveness of treatment based on the determination of safety and efficacy.Methods: The data source includes PubMed/Medline, Web of Science, EMBASE, Cochrane Library, from inception to 2 January 2022. Literature was screened according to the PICOS principle, followed by literature quality evaluation to assess the risk of bias. Finally, the outcome indicators of each study were extracted for combined analysis.Results: 9 studies were included in the current analysis. The results of the pooled analysis showed that the improvements in both primary and secondary indicators except for Bayley Scales of Infant and Toddler Development were more skewed towards stem cell therapy than the control group. In the subgroup analysis, the results showed that stem cell therapy significantly increased Gross Motor Function Measure (GMFM) scores of 3, 6, and 12 months. Besides, improvements in GMFM scores were more skewed toward umbilical cord mesenchymal stem cells, low dose, and intrathecal injection. Importantly, there was no significant difference in the adverse events (RR = 1.13; 95% CI = [0.90, 1.42]) between the stem cell group and the control group.Conclusion: The results suggested that stem cell therapy for cerebral palsy was safe and effective. Although the subgroup analysis results presented guiding significance in the selection of clinical protocols for stem cell therapy, high-quality RCTs validations are still needed.</p

Image2_Efficacy and safety of stem cell therapy in cerebral palsy: A systematic review and meta-analysis.TIF

Aim: Although the efficacy and safety of stem cell therapy for cerebral palsy has been demonstrated in previous studies, the number of studies is limited and the treatment protocols of these studies lack consistency. Therefore, we included all relevant studies to date to explore factors that might influence the effectiveness of treatment based on the determination of safety and efficacy.Methods: The data source includes PubMed/Medline, Web of Science, EMBASE, Cochrane Library, from inception to 2 January 2022. Literature was screened according to the PICOS principle, followed by literature quality evaluation to assess the risk of bias. Finally, the outcome indicators of each study were extracted for combined analysis.Results: 9 studies were included in the current analysis. The results of the pooled analysis showed that the improvements in both primary and secondary indicators except for Bayley Scales of Infant and Toddler Development were more skewed towards stem cell therapy than the control group. In the subgroup analysis, the results showed that stem cell therapy significantly increased Gross Motor Function Measure (GMFM) scores of 3, 6, and 12 months. Besides, improvements in GMFM scores were more skewed toward umbilical cord mesenchymal stem cells, low dose, and intrathecal injection. Importantly, there was no significant difference in the adverse events (RR = 1.13; 95% CI = [0.90, 1.42]) between the stem cell group and the control group.Conclusion: The results suggested that stem cell therapy for cerebral palsy was safe and effective. Although the subgroup analysis results presented guiding significance in the selection of clinical protocols for stem cell therapy, high-quality RCTs validations are still needed.</p

DataSheet1_Efficacy and safety of stem cell therapy in cerebral palsy: A systematic review and meta-analysis.PDF

Aim: Although the efficacy and safety of stem cell therapy for cerebral palsy has been demonstrated in previous studies, the number of studies is limited and the treatment protocols of these studies lack consistency. Therefore, we included all relevant studies to date to explore factors that might influence the effectiveness of treatment based on the determination of safety and efficacy.Methods: The data source includes PubMed/Medline, Web of Science, EMBASE, Cochrane Library, from inception to 2 January 2022. Literature was screened according to the PICOS principle, followed by literature quality evaluation to assess the risk of bias. Finally, the outcome indicators of each study were extracted for combined analysis.Results: 9 studies were included in the current analysis. The results of the pooled analysis showed that the improvements in both primary and secondary indicators except for Bayley Scales of Infant and Toddler Development were more skewed towards stem cell therapy than the control group. In the subgroup analysis, the results showed that stem cell therapy significantly increased Gross Motor Function Measure (GMFM) scores of 3, 6, and 12 months. Besides, improvements in GMFM scores were more skewed toward umbilical cord mesenchymal stem cells, low dose, and intrathecal injection. Importantly, there was no significant difference in the adverse events (RR = 1.13; 95% CI = [0.90, 1.42]) between the stem cell group and the control group.Conclusion: The results suggested that stem cell therapy for cerebral palsy was safe and effective. Although the subgroup analysis results presented guiding significance in the selection of clinical protocols for stem cell therapy, high-quality RCTs validations are still needed.</p

Table3_Efficacy and safety of stem cell therapy in cerebral palsy: A systematic review and meta-analysis.XLS

Aim: Although the efficacy and safety of stem cell therapy for cerebral palsy has been demonstrated in previous studies, the number of studies is limited and the treatment protocols of these studies lack consistency. Therefore, we included all relevant studies to date to explore factors that might influence the effectiveness of treatment based on the determination of safety and efficacy.Methods: The data source includes PubMed/Medline, Web of Science, EMBASE, Cochrane Library, from inception to 2 January 2022. Literature was screened according to the PICOS principle, followed by literature quality evaluation to assess the risk of bias. Finally, the outcome indicators of each study were extracted for combined analysis.Results: 9 studies were included in the current analysis. The results of the pooled analysis showed that the improvements in both primary and secondary indicators except for Bayley Scales of Infant and Toddler Development were more skewed towards stem cell therapy than the control group. In the subgroup analysis, the results showed that stem cell therapy significantly increased Gross Motor Function Measure (GMFM) scores of 3, 6, and 12 months. Besides, improvements in GMFM scores were more skewed toward umbilical cord mesenchymal stem cells, low dose, and intrathecal injection. Importantly, there was no significant difference in the adverse events (RR = 1.13; 95% CI = [0.90, 1.42]) between the stem cell group and the control group.Conclusion: The results suggested that stem cell therapy for cerebral palsy was safe and effective. Although the subgroup analysis results presented guiding significance in the selection of clinical protocols for stem cell therapy, high-quality RCTs validations are still needed.</p

MOESM9 of Ochratoxin A induces liver inflammation: involvement of intestinal microbiota

Additional file 9: Figure S9. The cecum microbial diversity and composition of transplant donors and recipients. a: Alpha diversity of intestinal microbiome in transplant donors and recipients. b: Relative abundance of bacteria at Phylum level. OTUs with an occurrence lower than 1% are not represented (n=7). c: Relative abundance of top 15 Genus in each group (n=7). d: Relative abundance of top 15 Species in each group (n=7). Data in a and b were analyzed by one-way ANOVA with Bonferroni’s multiple comparisons test *P<0.05. FMT (CON): ducks received CON group fecal microbiota. FMT (OTA): ducks received OTA group fecal microbiota