Altered intestinal microbiome and metabolome correspond to the clinical outcome of sepsis.

BACKGROUND: The gut microbiome plays a pivotal role in the progression of sepsis. However, the specific mechanism of gut microbiota and its metabolites involved in the process of sepsis remains elusive, which limits its translational application. METHOD: In this study, we used a combination of the microbiome and untargeted metabolomics to analyze stool samples from patients with sepsis enrolled at admission, then microbiota, metabolites, and potential signaling pathways that might play important roles in disease outcome were screened out. Finally, the above results were validated by the microbiome and transcriptomics analysis in an animal model of sepsis. RESULTS: Patients with sepsis showed destruction of symbiotic flora and elevated abundance of Enterococcus, which were validated in animal experiments. Additionally, patients with a high burden of Bacteroides, especially B. vulgatus, had higher Acute Physiology and Chronic Health Evaluation II scores and longer stays in the intensive care unit. The intestinal transcriptome in CLP rats illustrated that Enterococcus and Bacteroides had divergent profiles of correlation with differentially expressed genes, indicating distinctly different roles for these bacteria in sepsis. Furthermore, patients with sepsis exhibited disturbances in gut amino acid metabolism compared with healthy controls; namely, tryptophan metabolism was tightly related to an altered microbiota and the severity of sepsis. CONCLUSION: Alterations in microbial and metabolic features in the gut corresponded with the progression of sepsis. Our findings may help to predict the clinical outcome of patients in the early stage of sepsis and provide a translational basis for exploring new therapies.

Intravenous Vitamin C attenuates hemorrhagic shock-related renal injury through the induction of SIRT1 in rats.

To investigate the effect of intravenous Vitamin C (VC) on hemorrhagic shock (HS)-associated rat renal injury and the involved mechanism. Thirty SD rats were randomly assigned to the sham surgery (sham), hemorrhagic shock (HS), HS+100 mg/kg VC (H + VL), HS+500 mg/kg VC (H + VH) and HS+100 mg/kg VC + EX527 (H + VL + E) groups. Tissue and blood samples were collected 6 h after surgery. Kidney pathological changes were scored. Creatinine (CRE), blood urea nitrogen (BUN), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) levels in serum and Vitamin C levels and superoxide dismutase (SOD) activity and the ability to suppress hydroxyl radical (RAFHR) in plasma were measured. The expression of Sirtuin1 (SIRT1), Acetyl-NF-κB (Ace-NF-κB), heme oxygenase-1 (HO-1), TNF-α, and IL-1ß in tissues was analyzed by ELISA or western-blot. In the HS group, the kidney pathological score and CRE, BUN, TNF-α, and IL-1ß levels in serum were significantly higher than in the Sham group (P < 0.05), while SOD and RAFHR were significantly decreased in the plasma (P < 0.05). SOD activity and SIRT1 expression were remarkably lower in the kidney in the HS group than in the Sham group (P < 0.05), while MDA, TNF-α, and IL-1ß concentrations and Acetyl-NF-κB andHO-1 expression in the kidney showed a noteworthy increase compared to the Sham group (P < 0.05). Compared to the HS group, VC treatment led to a remarkable reduction in the kidney pathological score and CRE,BUN,TNF-α, and IL-1ß levels (P < 0.05), and a significant increase in Vitamin C, SOD, and RAFHR levels in the plasma (P < 0.05). Additionally, MDA, TNF-α, IL-1ß and Acetyl-NF-κB expression levels were decreased in the kidney (P < 0.05), while SOD, SIRT1 and HO-1 levels were notably enhanced. There were no differences between the H + VL and H + VH groups aside from plasma Vitamin C levels. The effect of Vitamin C was decreased after the addition of EX527, which inhibits SIRT1. Intravenous Vitamin C might attenuate HS-related renal injury via the SIRT1 pathway, and it appears that there were no differences in the effects between the high and low doses.

A senescence-based prognostic gene signature for colorectal cancer and identification of the role of SPP1-positive macrophages in tumor senescence.

Background: Senescence is significantly associated with cancer prognosis. This study aimed to construct a senescence-related prognostic model for colorectal cancer (CRC) and to investigate the influence of senescence on the tumor microenvironment. Methods: Transcriptome and clinical data of CRC cases were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Senescence-related prognostic genes detected by univariate Cox regression were included in Least Absolute Shrinkage and Selection Operator (LASSO) analysis to construct a model. The efficacy of the model was validated using the receiver operating characteristic (ROC) curve and survival analysis. Differentially expressed genes (DEGs) were identified and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed. CIBERSORT and Immuno-Oncology Biological Research (IOBR) were used to investigate the features of the tumor microenvironment. Single-cell RNA-seq data were used to investigate the expression levels of model genes in various cell types. Immunofluorescence staining for p21, SPP1, and CD68 was performed with human colon tissues. Results: A seven-gene (PTGER2, FGF2, IGFBP3, ANGPTL4, DKK1, WNT16 and SPP1) model was finally constructed. Patients were classified as high- or low-risk using the median score as the threshold. The area under the ROC curve (AUC) for the 1-, 2-, and 3-year disease-specific survival (DSS) were 0.731, 0.651, and 0.643, respectively. Survival analysis showed a better 5-year DSS in low-risk patients in the construction and validation cohorts. GO and KEGG analyses revealed that DEGs were enriched in extracellular matrix (ECM)-receptor interactions, focal adhesion, and protein digestion and absorption. CIBERSORT and IOBR analyses revealed an abundance of macrophages and an immunosuppressive environment in the high-risk subgroup. Low-risk patients had higher response rates to immunotherapy than high-risk patients. ScRNA-seq data revealed high expression of SPP1 in a subset of macrophages with strong senescence-associated secretory phenotype (SASP) features. Using CRC tumor tissues, we discovered that SPP1+ macrophages were surrounded by a large number of senescent tumor cells in high-grade tumors. Conclusion: Our study presents a novel model based on senescence-related genes that can identify CRC patients with a poor prognosis and an immunosuppressive tumor microenvironment. SPP1+ macrophages may correlate with cell senescence leading to poor prognosis.

Effect of high-dose intravenous vitamin C therapy on the prognosis in patients with moderately severe and severe acute pancreatitis: protocol of a prospective, randomized, double-blinded, placebo-controlled study.

Introduction: Acute pancreatitis is a common gastrointestinal disease. The mortality of patients affected by severe acute pancreatitis (SAP) remains high. It is unclear whether high-dose intravenous vitamin C (HDIVC) therapy could improve the prognosis of these patients. The current prospective, randomized, double-blinded, placebo-controlled study will explore the effect of high-dose intravenous vitamin C therapy on the prognosis in patients with moderately severe and severe acute pancreatitis. Methods and design: A total of 418 participants with moderately severe and severe acute pancreatitis who meet the eligible criteria will be randomly assigned in a 1:1 ratio to receive treatment with HDIVC (200 mg/kg/24 h) or placebo (saline) for a period of 7 days. The primary outcome is 28-day mortality in these patients. The secondary outcomes include organ functions and interventions, laboratory tests, healthcare, and 90-day mortality. Ethics and dissemination: This protocol was approved by the institutional ethics board of the Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Registration Number: 2019-90). The report of the study will be published in peer-reviewed journals and presented at conferences, both nationally and internationally. Clinical trial registration: Chinese Clinical Trial Registry (ChiCTR1900022022). Version 1.5.

High-dose vitamin C on sepsis: Protocol of a prospective, multi-centered, double-blinded, randomized, and placebo-controlled superiority study.

Background: Sepsis is an inflammatory syndrome with life-threatening organ dysfunction and high mortality. In the recent 10 years, high-dose intravenous injection of vitamin C, the first-line antioxidant of humans, has received highlighted attention in the field of critical care. The study aims to examine the efficacy and safety of high-dose intravenous injection of vitamin C in the treatment of sepsis. Methods and design: Here, we are conducting a prospective, multi-centered, double-blinded, randomized, and placebo-controlled superiority study named High-Dose Vitamin C on Sepsis (HDVCOS). A total of 620 participants diagnosed with sepsis in four participating sites across China that satisfy the eligibility criteria will be randomized at a ratio of 1:1 to receive treatment with a high-dose intravenous injection of vitamin C (200 mg/kg/24 h) or placebo (saline) for 4 days. The primary outcome is 28 days of mortality. The secondary outcomes include the incidence of organ failure, Sequential Organ Failure Assessment (SOFA) score change, organ support, the relationship between plasma vitamin C concentration and outcomes, and adverse events. Conclusion: The findings of this study will provide potential evidence for high-dose intravenous injection of vitamin C in the treatment of sepsis. Clinical trial registration: [http://www.chictr.org.cn/showprojen.aspx?proj=29851], identifier [ChiCTR1800017633].

Bandgap-Coupled Template Autocatalysis toward the Growth of High-Purity sp2 Nanocarbons.

Extraordinary properties and great application potentials of carbon nanotubes (CNT) and graphene fundamentally rely on their large-scale perfect sp2 structure. Particularly for high-end applications, ultralow defect density and ultrahigh selectivity are prerequisites, for which metal-catalyzed chemical vapor deposition (CVD) is the most promising approach. Due to their structure and peculiarity, CNTs and graphene can themselves provide growth templates and nonlocal dual conductance, serving as template autocatalysts with tunable bandgap during the CVD. However, current growth kinetics models all focus on the external factors and edges. Here, the growth kinetics of sp2 nanocarbons is elaborated from the perspective of template autocatalysis and holistic electronic structure. After reviewing current growth kinetics, various representative works involving CVD growth of different sp2 nanocarbons are analyzed, to reveal their bandgap-coupled kinetics and resulting selective synthesis. Recent progress is then reviewed, which has demonstrated the interlocking between the atomic assembly rate and bandgap of CNTs, with an explicit volcano dependence whose peak would be determined by the environment. In addition, the topological protection for perfect sp2 structure and the defect-induced perturbation for the interlocking are discussed. Finally, the prospects for the kinetic selective growth of perfect nanocarbons are proposed.

Fluid resuscitation via colon alleviates systemic inflammation in rats with early-stage severe acute pancreatitis.

Fluid resuscitation via colon (FRVC) is a complementary therapeutic procedure for early-stage cases of severe acute pancreatitis (SAP). The expression of intestinal dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) regulates systemic inflammation. This study aimed to investigate the effect of FRVC on the expression of DC-SIGN in the colon tissue of SAP rats and its effect on the early response of systemic inflammatory and multiple organ injury. SAP was induced in rats via retrograde injection of sodium taurocholate into the biliopancreatic duct. DC-SIGN expression of appeared in the proximal and distal colon. Histological characteristics and inflammatory cytokines were examined to compare the effect of FRVC and intravenous fluid resuscitation (IVFR). The results showed that DC-SIGN expression in the proximal colon increased in a time-dependent manner in the early-stage of SAP rats. FRVC inhibited DC-SIGN expression in the proximal colon. Both FRVC and IVFR alleviated histological injuries of the pancreas and colon. However, FRVC had an advantage over IVFR in alleviating lung injury and reducing serum TNF-α, IL-6 and LPS. These results suggest that FRVC treatment might help suppress systemic inflammation and prevent subsequent organ failure in early-stage SAP rats likely through inhibiting DC-SIGN expression in the proximal colon.

High Dose Intravenous Vitamin C for Preventing The Disease Aggravation of Moderate COVID-19 Pneumonia. A Retrospective Propensity Matched Before-After Study.

Background: Coronavirus disease 2019 (COVID-19) pandemic is continuing to impact multiple countries worldwide and effective treatment options are still being developed. In this study, we investigate the potential of high-dose intravenous vitamin C (HDIVC) in the prevention of moderate COVID-19 disease aggravation. Methods: In this retrospective before-after case-matched clinical study, we compare the outcome and clinical courses of patients with moderate COVID-19 patients who were treated with an HDIVC protocol (intravenous injection of vitamin C, 100 mg/kg/day, 1 g/h, for 7 days from admission) during a one-month period (between March 18 and april 18, 2020, HDIVC group) with a control group treated without the HDIVC protocol during the preceding two months (January 18 to March 18, 2020). Patients in the two groups were matched in a 1:1 ratio according to age and gender. Results: The HDIVC and control groups each comprised 55 patients. For the primary outcomes, there was a significant difference in the number of patients that evolved from moderate to severe type between the two groups (HDIVC: 4/55 vs. control: 12/55, relative risk [RR] = 0.28 [0.08, 0.93], P = 0.03). Compared to the control group, there was a shorter duration of systemic inflammatory response syndrome (SIRS) (P = 0.0004) during the first week and lower SIRS occurrence (2/21 vs 10/22, P = 0.0086) on Day 7 (6-7 days after admission). In addition, HDIVC group had lower C-reactive protein levels (P = 0.005) and higher number of CD4+ T cells from Day 0 (on admission) to Day 7 (P = 0.04)." The levels of coagulation indicators, including activated partial thromboplastin time and D-dimer were also improved in the HDIVC compared to the control group on Day 7. Conclusion: HDIVC may be beneficial in limiting disease aggravation in the early stage of COVID-19 pneumonia, which may be related to its improvements on the inflammatory response, immune function and coagulation function. Further randomized controlled trials are required to augment these findings.

Monochromatic Carbon Nanotube Tangles Grown by Microfluidic Switching between Chaos and Fractals.

The nature of chaos is in that elusive flow that is an advanced order out of our vision. It is wise to take advantage of chaos after recognizing or modifying its unique fractal properties. Here, a magnetron weaving strategy was developed for producing chaotic but monochromatic carbon nanotube tangles (CNT-Ts) under Kelvin-Helmholtz instability (KHI). The self-similarity characteristic facilitated individual ultralong CNTs to manipulate their entropy-driven fractal geometry, resulting in ∼104 µm2 CNT-Ts with variable curvature radius. In addition, based on the rate-selected mechanism, 85% metallic and ∼100% semiconducting CNT-Ts were synthesized and separated simultaneously at different length positions. After ex situ modifying their fractal into aligned CNTs with hydrogel, these CNT-Ts delivered a current of 10 µA µm-1 in transistors with an on/off ratio >107. It has provided the third route as a paradigm of applying one-dimensional nanomaterials by switching between chaos and fractal, in parallel with that of direct synthesis and postseparation.

Cardiac indicator CK-MB might be a predictive marker for severity and organ failure development of acute pancreatitis.

BACKGROUND: The prediction of severe acute pancreatitis (SAP) is the key to providing timely and targeted intensive care for acute pancreatitis (AP). The heart is one of multiple organs involved in the early stage of SAP, but the predictive ability of cardiac dysfunction for SAP remains elusive. We sought to determine if the serum levels of three cardiac indicators (CI) including N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin I (cTNI), and creatine kinase myocardial band (CK-MB) at admission could predict the occurrence of SAP and the development of related organ failure (OF). METHODS: A retrospective, single-center cohort study was conducted on the files of patients presenting to the emergency intensive care unit and medical ward of a regional hospital in Shanghai. Patients diagnosed as having AP and who met the 2012 Atlanta guideline were admitted within 48 hours after disease onset. RESULTS: Of the 670 AP patients screened, 238 were enrolled into the study and divided into mild acute pancreatitis (MAP) (n=59), moderate severe acute pancreatitis (MSAP) (n=123), and SAP (n=56) groups. No significant difference was found in baseline age, gender, duration from disease onset to admission, comorbidity, or substance abuse. As the levels of three CIs were significantly higher in the SAP group than in the MAP and MSAP groups, the enrolled patients were regrouped into non-SAP and SAP groups for predictive evaluation. Multivariate analysis and nomogram modelling showed that CK-MB, but not cTNI or NT-proBNP predicted the occurrence of SAP [area under curve (AUC) =0.805, confidence interval (CI): 0.794-0.905]. Specifically, 89 patients with OF (Modified Marshall score ≥2) upon admission were selected and CK-MB was shown to predict (AUC =0.805, CI: 0.794-0.905) persistent OF (n=48, duration of OF >48 hours) compared to transient organ failure (TOF) (n=41, duration of OF <48 hours). CONCLUSIONS: CIs including NT-proBNP, cTNI, and CK-MB were elevated in the early stage of AP. CK-MB might be used as an efficient predictive biomarker for SAP occurrence and OF development at admission.

TUDCA Ameliorates Liver Injury Via Activation of SIRT1-FXR Signaling in a Rat Hemorrhagic Shock Model.

OBJECTIVE: The aim of this study was to investigate the changes of bile acids in the liver during hemorrhagic shock (HS) and their potential to attenuate liver injury via activation of SIRT1 (sirtuin 1)-FXR (farnesoid X receptor) signaling. METHODS: A Sprague-Dawley (SD) rat HS model was established, whereas HepG2 cells were hypoxically cultured to simulate HS in vitro. Liver bile acids (BA) were profiled with ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). FXR expression was detected by western blot and immunohistochemistry. The mRNA levels of SIRT1 and FXR were detected by polymerase chain reaction. Protein expression of SIRT1, FoxM1, NF-κB, acetyl-NF-κB, p53, and acetyl-p53 was analyzed by western blot. Hepatocyte apoptosis and proliferation were measured by TUNEL assay and Ki-67 staining, respectively. Serum and supernatant cytokines were analyzed using ELISA assays. Liver injury was also assessed. To investigate the possible mechanisms, SIRT1 agonist (SRT1720), SIRT1 inhibitor (EX527), and FXR inhibitor (Z-guggulsterone) were used. RESULTS: Tauroursodeoxycholic acid (TUDCA) in the liver decreased significantly after HS. SIRT1 and FXR expression was time-dependently downregulated by HS or hypoxia condition. TUDCA upregulated SIRT1-FXR activity, which inhibited expression and acetylation of NF-κB and p53 and increased FoxM1 expression, leading to decreased inflammatory response and apoptosis and increased proliferative capacity in hepatocytes, and attenuation of liver injury. EX527 pretreatment reversed the protective effect of TUDCA. Moreover, Z-guggulsterone supplementation decreased the protective effect of TUDCA in vitro. CONCLUSION: TUDCA in the liver decreased during HS. TUDCA supplementation might attenuate HS-induced liver injury by upregulating SIRT1-FXR signaling.

Super-durable ultralong carbon nanotubes.

Fatigue resistance is a key property of the service lifetime of structural materials. Carbon nanotubes (CNTs) are one of the strongest materials ever discovered, but measuring their fatigue resistance is a challenge because of their size and the lack of effective measurement methods for such small samples. We developed a noncontact acoustic resonance test system for investigating the fatigue behavior of centimeter-long individual CNTs. We found that CNTs have excellent fatigue resistance, which is dependent on temperature, and that the time to fatigue fracture of CNTs is dominated by the time to creation of the first defect.

High-dose vitamin C alleviates pancreatic injury via the NRF2/NQO1/HO-1 pathway in a rat model of severe acute pancreatitis.

BACKGROUND: Oxidative stress plays a pivotal role in the progress of severe acute pancreatitis (SAP). Vitamin C (VC) is the most important antioxidant in plasma. However, the effects of an intravenous administration of high-dose VC and the mechanisms by which it exerts its antioxidant function in an experimental model of SAP have not been determined. METHODS: Sodium taurocholate was used to induce rat pancreatic injury and AR42J cells injury. After the establishment of SAP model, SAP rat and injured AR42J cells were treated with VC. For the injured AR42J cells, small interfering RNA-mediated knockdown of NRF2 was conducted after VC treatment. The histopathological characteristics, the apoptosis of pancreatic acinar cells, oxidative stress markers and levels of enzymes, biochemical indicators, and inflammatory cytokines were examined in vivo and in vitro. Furthermore, the mortality of rats was assessed. RESULTS: In vivo and in vitro results demonstrated that VC treatment ameliorated apoptosis of pancreatic acinar cells, as evidenced by the increase in Bcl-2, Bcl-XL, and MCL-1 expressions and decrease in Bax and cleaved caspase-3 expression along with decreased TUNEL-positive cells. Also, we found that the elevation of MDA and decrease of SOD, GPx, GSH/GSSG, and T-AOC induced by SAP were reversed by VC treatment in vivo and in vitro, and VC treatment increased expressions of Nrf2, NQO1, and HO-1 in SAP model at protein and gene level, indicating that VC attenuated oxidative stress via the NRF2/NQO1/HO-1 pathway. Meanwhile, it was found that sodium taurocholate significantly induced the release of amylase, lipase, IL-1ß, and IL-6 in rat plasma and AR42J cells, which were declined by VC treatment. In vitro results also revealed that these alterations in sodium taurocholate-injured AR42J cells due to VC treatment was attenuated by NRF2 knockdown. In addition, VC at a dose of 500 mg/kg decreased the levels of lactic acid, Cre, NGAL, AST, and ALT in the plasma of SAP rats, suggesting the improvement of renal and pancreatic injury and liver function of SAP rats. Furthermore, the mortality of SAP rats was 50%, which declined to 30% after VC treatment. CONCLUSIONS: The present study suggests that high-dose of VC ameliorate pancreatic injury of SAP via the NRF2/NQO1/HO-1 pathway to inhibit oxidative stress.

Storage of Mechanical Energy Based on Carbon Nanotubes with High Energy Density and Power Density.

Energy storage in a proper form is an important way to meet the fast increase in the demand for energy. Among the strategies for storing energy, storage of mechanical energy via suitable media is widely utilized by human beings. With a tensile strength over 100 GPa, and a Young's modulus over 1 TPa, carbon nanotubes (CNTs) are considered as one of the strongest materials ever found and exhibit overwhelming advantages for storing mechanical energy. For example, the tensile-strain energy density of CNTs is as high as 1125 Wh kg-1 . In addition, CNTs also exhibit great potential for fabricating flywheels to store kinetic energy with both high energy density (8571 Wh kg-1 ) and high power density (2 MW kg-1 to 2 GW kg-1 ). Here, an overview of some typical mechanical-energy-storage systems and materials is given. Then, theoretical and experimental studies on the mechanical properties of CNTs and CNT assemblies are introduced. Afterward, the strategies for utilizing CNTs to store mechanical energy are discussed. In addition, macroscale production of CNTs is summarized. Finally, future trends and prospects in the development of CNTs used as mechanical-energy-storage materials are presented.

Rate-selected growth of ultrapure semiconducting carbon nanotube arrays.

Carbon nanotubes (CNTs) are promising candidates for smart electronic devices. However, it is challenging to mediate their bandgap or chirality from a vapor-liquid-solid growth process. Here, we demonstrate rate-selected semiconducting CNT arrays based on interlocking between the atomic assembly rate and bandgap of CNTs. Rate analysis confirms the Schulz-Flory distribution which leads to various decay rates as length increases in metallic and semiconducting CNTs. Quantitatively, a nearly ten-fold faster decay rate of metallic CNTs leads to a spontaneous purification of the predicted 99.9999% semiconducting CNTs at a length of 154 mm, and the longest CNT can be 650 mm through an optimized reactor. Transistors fabricated on them deliver a high current of 14 µA µm-1 with on/off ratio around 108 and mobility over 4000 cm2 V-1 s-1. Our rate-selected strategy offers more freedom to control the CNT purity in-situ and offers a robust methodology to synthesize perfectly assembled nanotubes over a long scale.

Human adipose tissue-derived stem cells inhibit the activity of keloid fibroblasts and fibrosis in a keloid model by paracrine signaling.

BACKGROUND: Human adipose tissue-derived mesenchymal stem cells (ASCs) have potential utility as modulators of the regeneration of tissue that is inflamed or scarred secondary to injuries such as burns or trauma. However, the effect of ASCs on one particular type of scarring, keloidal disease, remains unknown. The absence of an optimal model for investigation has hindered the development of an effective therapy using ASCs for keloids. OBJECTIVE: To investigate the influence of ASCs on angiogenesis, extracellular matrix deposition, and inflammatory cell influx in keloids. METHODS: We analyzed the proliferation, migration, and apoptosis of human keloid-derived fibroblasts treated with a starvation-induced, conditioned medium from ASCs (ASCs-CM). This was achieved by Brdu proliferation assay, a validated co-culture migration assay, and flow cytometry, respectively. To assess the change in phenotype to a pro-fibrotic state, fibroblasts were analyzed by real-time PCR and contraction assay. A keloid implantation animal model was used to assess the paracrine effect of ASCs histochemically and immunohistochemically on scar morphology, collagen deposition, inflammatory cell composition, and blood vessel density. In tandem, an antibody-based array was used to identify protein concentration in the presence of ASCs-CM at time point 0, 24, and 48h. RESULTS: ASCs-CM inhibited the proliferation and collagen synthesis of human keloid-derived fibroblasts. ASCs-CM was associated with reduced inflammation and fibrosis in the keloid implantation model. Thirty-four cytokines were differentially regulated by ASCs-CM at 24h. These included molecules associated with apoptosis, matrix metalloproteases, and their inhibitors. The same molecules were present at relatively higher concentrations at the 48h timepoint. CONCLUSION: These results suggest that ASCs are associated with the inhibition of fibrosis in keloids by a paracrine effect. This phenomenon may have utility as a therapeutic approach in the clinical environment.