Supplementary Material for: Hepatocyte Growth Factor Promotes Differentiation Potential and Stress Response of Human Stem Cells from Apical Papilla

Harsh local microenvironment, such as hypoxia and lack of instructive clues for transplanted stem cells, presents the serious obstacle for stem cell therapies’ efficacy. Therefore, continued efforts have been taken to improve stem cells’ viability and plasticity. Hepatocyte growth factor (HGF) have previously been reported to mitigate complications of various human diseases in animal model studies and in some clinical trials. Besides, human stem cells from root apical papilla (SCAP) are deemed a better resource of mesenchymal stem cells due to derived stem cells holding greater amplification ability in vitro compared with those from other dental resources. To move forward, evaluating effects and understanding underlying molecular mechanisms of HGF on SCAP for periodontal regeneration are needed. In this study, HGF was transgenic expressed in SCAP, and it was found that HGF enhanced osteo/dentinogenic differentiation capacity of SCAP compared with those non-treated control in an ectopic mineralization model. Moreover, HGF reduced apoptosis of SCAP under both normoxia and hypoxia condition, whereas combination of HGF and hypoxia exposure had inhibitory effects on cell proliferation during an eight-day in vitro culture period. Transcriptome analysis further revealed that suppressed cell cycle progression and activated BMP/ TGFβ, Hedgehog, WNT, FGF, HOX and other morphogen family members upon HGF overexpression, which may render SCAP recapitulate part of neural crest stem cells characteristics. Moreover, strengthened stress-response modulation such as unfolded protein response, macroautophagy and anti-apoptotic molecules might explain increased viability of SCAP. In all, our results imply that these potential mechanisms underlying HGF promoting SCAP differentiation could be further elucidated and harnessed to improve dental tissue regeneration

Supplementary Material for: The global incidence rate of pemphigus vulgaris: a systematic review and meta-analysis

Background: Pemphigus vulgaris is a life-threatening autoimmune bullous disease characterized by flaccid blister formation. As there has been no macroscopic assessment of epidemiological characteristics, its disease burden in the general population remains unknown. Objectives: To assess the global incidence rate of pemphigus vulgaris in the general population. Methods: The search was conducted in databases including Medline, Embase, Web of Science, and The Cochrane Library from inception to May 1st, 2022. We included original studies that either reported incidence of pemphigus vulgaris or provided raw data for calculating. Studies based on a specific population instead of the general population were excluded. Individual studies were summarized using random-effects mode. The pooled incidence rate of pemphigus vulgaris among the general population and subgroups were obtained. Heterogeneity (I2 statistic) was assessed with the χ2 test on Cochrane’s Q statistic. Results: 29 studies were eligible for final analysis and the pooled incidence rate of pemphigus vulgaris was 2.83 per million person-years (95%CI, 2.14-3.61). The incidence rate was similar between men and women and remained stable in the past half-century. Southern Asia showed the highest rate among subcontinents that had more than one study conducted as 4.94 per million person-years (95%CI, 2.55-8.10). Economic levels do not seem to have any bearing on incidence. Conclusions: Despite the substantial heterogeneity among studies, this meta-analysis revealed the worldwide incidence rate of pemphigus vulgaris for the first time and may assist in assessing global disease burden and promoting health policy

Supplementary Material for: The global incidence rate of pemphigus vulgaris: a systematic review and meta-analysis

Background: Pemphigus vulgaris is a life-threatening autoimmune bullous disease characterized by flaccid blister formation. As there has been no macroscopic assessment of epidemiological characteristics, its disease burden in the general population remains unknown. Objectives: To assess the global incidence rate of pemphigus vulgaris in the general population. Methods: The search was conducted in databases including Medline, Embase, Web of Science, and The Cochrane Library from inception to May 1st, 2022. We included original studies that either reported incidence of pemphigus vulgaris or provided raw data for calculating. Studies based on a specific population instead of the general population were excluded. Individual studies were summarized using random-effects mode. The pooled incidence rate of pemphigus vulgaris among the general population and subgroups were obtained. Heterogeneity (I2 statistic) was assessed with the χ2 test on Cochrane’s Q statistic. Results: 29 studies were eligible for final analysis and the pooled incidence rate of pemphigus vulgaris was 2.83 per million person-years (95%CI, 2.14-3.61). The incidence rate was similar between men and women and remained stable in the past half-century. Southern Asia showed the highest rate among subcontinents that had more than one study conducted as 4.94 per million person-years (95%CI, 2.55-8.10). Economic levels do not seem to have any bearing on incidence. Conclusions: Despite the substantial heterogeneity among studies, this meta-analysis revealed the worldwide incidence rate of pemphigus vulgaris for the first time and may assist in assessing global disease burden and promoting health policy

Supplementary Material for: The global incidence rate of pemphigus vulgaris: a systematic review and meta-analysis

Background: Pemphigus vulgaris is a life-threatening autoimmune bullous disease characterized by flaccid blister formation. As there has been no macroscopic assessment of epidemiological characteristics, its disease burden in the general population remains unknown. Objectives: To assess the global incidence rate of pemphigus vulgaris in the general population. Methods: The search was conducted in databases including Medline, Embase, Web of Science, and The Cochrane Library from inception to May 1st, 2022. We included original studies that either reported incidence of pemphigus vulgaris or provided raw data for calculating. Studies based on a specific population instead of the general population were excluded. Individual studies were summarized using random-effects mode. The pooled incidence rate of pemphigus vulgaris among the general population and subgroups were obtained. Heterogeneity (I2 statistic) was assessed with the χ2 test on Cochrane’s Q statistic. Results: 29 studies were eligible for final analysis and the pooled incidence rate of pemphigus vulgaris was 2.83 per million person-years (95%CI, 2.14-3.61). The incidence rate was similar between men and women and remained stable in the past half-century. Southern Asia showed the highest rate among subcontinents that had more than one study conducted as 4.94 per million person-years (95%CI, 2.55-8.10). Economic levels do not seem to have any bearing on incidence. Conclusions: Despite the substantial heterogeneity among studies, this meta-analysis revealed the worldwide incidence rate of pemphigus vulgaris for the first time and may assist in assessing global disease burden and promoting health policy

Supplementary Material for: Mortality of Peritoneal Dialysis versus Hemodialysis in Older Adults: An Updated Systematic Review and Meta-Analysis

Introduction. The optimal choice of dialysis modality remains contentious in older adults threatened by advanced age and high risk of comorbidities. Methods. We conducted a systematic review and meta-analysis of cohort and case-control studies to assess mortality risk between peritoneal dialysis (PD) and hemodialysis (HD) in older adults using PubMed, Embase, and the Cochrane Library database from inception to June 1, 2022. The outcome of interest is all-cause mortality. Results. Thirty-one eligible studies with >774,000 older patients were included. Pooled analysis showed that PD had a higher mortality rate than HD in older dialysis population (HR 1.17, 95% CI 1.10-1.25). When stratified by co-variables, our study showed an increased mortality risk of PD versus HD in older patients with diabetes mellitus or comorbidity, who underwent longer dialysis duration (more than 3 years), or who started dialysis before 2010. However, definitive conclusions were constrained by significant heterogeneity. Conclusion. From the survival point of view, caution is needed to employ peritoneal dialysis for long-term use in older populations with diabetes mellitus or comorbid conditions. However, a tailored treatment choice needs to take account of what matters to older adults at an individual level, especially in the context of limited survival improvements and loss of quality of life. Further research is still awaited to conclude this topic

Supplementary Material for: The global incidence rate of pemphigus vulgaris: a systematic review and meta-analysis

Background: Pemphigus vulgaris is a life-threatening autoimmune bullous disease characterized by flaccid blister formation. As there has been no macroscopic assessment of epidemiological characteristics, its disease burden in the general population remains unknown. Objectives: To assess the global incidence rate of pemphigus vulgaris in the general population. Methods: The search was conducted in databases including Medline, Embase, Web of Science, and The Cochrane Library from inception to May 1st, 2022. We included original studies that either reported incidence of pemphigus vulgaris or provided raw data for calculating. Studies based on a specific population instead of the general population were excluded. Individual studies were summarized using random-effects mode. The pooled incidence rate of pemphigus vulgaris among the general population and subgroups were obtained. Heterogeneity (I2 statistic) was assessed with the χ2 test on Cochrane’s Q statistic. Results: 29 studies were eligible for final analysis and the pooled incidence rate of pemphigus vulgaris was 2.83 per million person-years (95%CI, 2.14-3.61). The incidence rate was similar between men and women and remained stable in the past half-century. Southern Asia showed the highest rate among subcontinents that had more than one study conducted as 4.94 per million person-years (95%CI, 2.55-8.10). Economic levels do not seem to have any bearing on incidence. Conclusions: Despite the substantial heterogeneity among studies, this meta-analysis revealed the worldwide incidence rate of pemphigus vulgaris for the first time and may assist in assessing global disease burden and promoting health policy

Erratum: Ischemic Preconditioning Attenuates Renal Ischemia-Reperfusion Injury by Inhibiting Activation of IKKβ and Inflammatory Response

<i>Background:</i> Renal ischemia-reperfusion (I/R) injury is a major cause of acute renal failure (ARF). The transcription factor nuclear factor-κB (NF-κB) has been implicated as a key mediator of reperfusion injury. Activation of NF-κB is dependent upon the phosphorylation of its inhibitor, IκB, by the specific inhibitory κB kinase (IKK) subunit, IKKβ. We hypothesized that ischemic preconditioning (IPC) reduces acute renal damage following I/R injury by inhibiting activation of IKKβ. As neutrophil gelatinase-associated lipocalin (NGAL), an early predictive biomarker of acute kidney injury, is regulated by NF-κB, we approached the relationship between NGAL and IKKβ. <i>Method:</i> Thirty male Sprague-Dawley rats were randomly divided into 3 groups after right kidney nephrectomy. Group A rats were sham-operated controls. Group B rats were 45-min ischemic in the left renal artery while Group C rats were pre-treated with 3 cycles of 2-min ischemia and 5-min reperfusion. All the rats were sacrificed at 24 h after reperfusion. We harvested kidneys and serum to do further analysis, including histological and functional parameters, expressions of NGAL and IKKβ in renal tissues. <i>Results:</i> Compared with rats subjected to I/R injury, pre-treated rats had a significant decrease in serum creatinine level (Scr) and tubulointerstitial injury scores (Scr, 86.79 ± 12.98 vs. 205.89 ± 19.16 μmol/l, p < 0.01; tubulointerstitial injury scores, 1.3 ± 0.48 vs. 3.8 ± 0.79, p < 0.01). In addition, expressions of IKKβ (0.95 ± 0.21 vs. 1.74 ± 0.17, p < 0.05) and NGAL (1.71 ± 0.032 vs. 2.66 ± 0.078, p < 0.05) at renal tubule in pre-treated rats were attenuated significantly compared with rats subjected to ischemia-reperfusion injury. Moreover, our study showed that IKKβ and NGAL were in positive correlation (R = 0.965 > R_0.01(30) = 0.448, p < 0.01). <i>Conclusions:</i> The evidence suggests that IKKβ may play a role in renal I/R injury and give rise to the generation of NGAL. It appears that IPC may attenuate renal injury and the expression of NGAL following acute I/R injury. IKKβ may offer a clinically accessible target for preventing renal injury following I/R

Supplementary Material for: Association between Toll-Like Receptor 4 T399I Gene Polymorphism and the Susceptibility to Crohn’s Disease: A Meta-Analysis of Case-Control Studies

<b><i>Background/Aims:</i></b> This article was undertaken to investigate the association of toll-like receptor 4 (TLR4) polymorphism (Thr399Ile) and risk of Crohn’s disease (CD) by performing a meta-analysis.<b><i> Methods:</i></b> Articles were chosen based on PubMed, Embase, China National Knowledge Internet, and Chinese Wanfang databases (up to 12th October 2016). Specific inclusion criteria were used to evaluate articles. Meta-analysis was performed by using a random or fixed effect model. Fifteen eligible case-control studies were finally included into this meta-analysis. We estimated the summary OR with its corresponding 95% CI to assess the association.<b><i> Results:</i></b> Summary results of this meta-analysis showed a moderate association between the TLR4 T399I polymorphism and the risk of CD (allele model: OR 1.26, 95% CI 1.06–1.50, <i>p</i> = 0.009; heterozygote model: OR 1.36, 95% CI 1.11–1.66, <i>p</i> = 0.003; dominant model: OR 1.35, 95% CI 1.10–1.64, <i>p</i> = 0.004; homozygote model: OR 1.08, 95% CI 0.44–2.64, <i>p</i> = 0.866; recessive model: OR 0.97, 95% CI 0.40–2.35, <i>p</i> = 0.946). Stratified analysis on geographical area, ethnicity, and genotypic methods suggested that the polymorphism was associated with increased risk of CD in Asia and Asians, and “T” allele only moderately increased CD risk within polymerase chain reaction-restricted fragment length polymorphism. <b><i>Conclusions:</i></b> Our meta-analysis suggests that TLR4 T399I polymorphism is moderately associated with susceptibility to CD, and more studies are needed to confirm our conclusion

Erratum: Down-Regulation of MiR-30c Promotes the Invasion of Non-Small Cell Lung Cancer by Targeting MTA1

<b><i>Background: </i></b>The connection between microRNA expression and lung cancer development has been identified in recent literature. However, the mechanism of microRNA has been poorly elucidated in non-small-cell lung cancer (NSCLC). <b><i>Methods and Results: </i></b>Comparing with adjacent tissues (n=75), miR-30c has a lower expression in lung cancer specimens (n=75). The knockdown of miR-30c enhanced the invasion of A549 cells; meanwhile, the overexpression of miR-30c could reverse the effect of the knockdown of miR-30c <i>in vitro</i>. A luciferase assay revealed that miR-30c was directly bound to the 3‘-untranslated regions (3‘-UTR) of MTA1. QRT-PCR and western blot shows MTA1 was up-regulated in mRNA and protein levels. The effect taken on the invasion of NSCLC by overexpression of MTA1 works the same as down-regulated miR-30c. <b><i>Conclusion: </i></b>miR-30c may play a pivotal role in controlling lung cancer invasion through regulating MTA1in NSCLC

Supplementary Material for: Natural History of Postoperative Nonfunctioning Pituitary Adenomas: A Systematic Review and Meta-Analysis

<b><i>Objective:</i></b> Previous studies attempting to define the natural history of postoperative nonfunctioning pituitary adenomas (pNFPAs) were somewhat limited by selection bias and/or small numbers and/or lack of consistency among the study findings. The aim of this study was to scrutinize the literature in order to analyze the natural history of pNFPAs. <b><i>Methods:</i></b> Electronic database including MEDLINE, PubMed and Cochrane CENTRAL were searched. The literature relating to the patients with pNFPAs without postoperative radiotherapy and pharmacotherapy was collected. Eligible studies reported on the rate of tumor recurrence, the tumor growth-free survival rate (TGFSR) at 5 and 10 years, and/or the residual tumor volume doubling time (TVDT). <b><i>Results:</i></b> 19 studies met the criteria. The pNFPAs were divided into two groups: the pooled recurrence rate of group I without detectable residual tumor (371 patients) was 12% (95% CI 6–19%), the TGFSR at 5 and 10 years were 96% (95% CI 89–99%) and 82% (95% CI 65–94%), respectively. The pooled recurrence rate of group II with residual tumor (600 patients) was 46% (95% CI 36–56%), the TGFSR at 5 and 10 years were 56% (95% CI 41–71%) and 40% (95% CI 27–53%), respectively. The mean TVDT was 3.4 years (95% CI 2.4–4.5 years). <b><i>Conclusions:</i></b> pNFPAs, with or without detectable residual tumor, need stratification of treatment and radiological/endocrinological follow-up strategy. According to the TVDT, residual tumor regrowth is very slow, which permits an extensive and safe follow-up program for most patients