Persimmon Fiber-Rich Ingredients Promote Anti-Inflammatory Responses and the Growth of Beneficial Anti-Inflammatory Firmicutes Species from the Human Colon.

Persimmon fruit processing-derived waste and by-products, such as peels and pomace, are important sources of dietary fiber and phytochemicals. Revalorizing these by-products could help promote circular nutrition and agricultural sustainability while tackling dietary deficiencies and chronic diseases. In this study, fiber-rich fractions were prepared from the by-products of Sharoni and Brilliant Red persimmon varieties. These fractions were quantified for their phenolic composition and assessed for their ability to promote the growth of beneficial human colonic Firmicutes species and for their in vitro anti-inflammatory potential. Gallic and protocatechuic acids, delphinidin, and cyanidin were the main phenolics identified. Faecalibacterium prausnitzii strains showed significantly higher growth rates in the presence of the Brilliant Red fraction, generating more than double butyrate as a proportion of the total short-chain fatty acids (39.5% vs. 17.8%) when compared to glucose. The fiber-rich fractions significantly decreased the inflammatory effect of interleukin-1ß in Caco-2 cells, and the fermented fractions (both from Sharoni and Brilliant Red) significantly decreased the inflammatory effect of interleukin-6 and tumor necrosis factor-α in the RAW 264.7 cells. Therefore, fiber-rich fractions from persimmon by-products could be part of nutritional therapies as they reduce systemic inflammation, promote the growth of beneficial human gut bacteria, and increase the production of beneficial microbial metabolites such as butyrate.

Evaluation of the Impact of the Ripening Stage on the Composition and Antioxidant Properties of Fruits from Organically Grown Tomato (Solanum lycopersicum L.) Spanish Varieties.

Tomato (Solanum lycopersicum L.) is a widely cultivated horticultural crop. It belongs to the Solanaceae family and is known for its high concentration of essential nutrients, including vitamins, minerals, and bioactive compounds with antioxidant properties. The Mediterranean countries, including Italy, Spain, and Greece, have a diverse range of tomato landraces. Assessing the nutritional and bioactive composition of different tomato varieties and their ripening stages is crucial to determine their suitability for the market. Therefore, the aim of this study was to investigate the effect of ripening on nutritional composition (including carotenoids and polyphenols content) and antioxidant activities of fruits of three specific tomato varieties grown in Spain: Josefina and Karelya, which are cherry-like tomatoes, and Muchamiel, a type of salad tomato. In addition to evaluating their characteristics and composition (including carotenoids and polyphenol content), the antioxidant activities of these varieties at three different ripening stages were quantified. As expected, the results reveal that, as the tomatoes matured, their antioxidant capacity increased along with higher levels of carotenoids and polyphenols. Interestingly, cherry-like tomatoes showed a higher antioxidant activity than the salad tomatoes. This investigation emphasizes the role of fruit ripening in increasing carotenoid levels, which contribute to the antioxidant activity of three tomato varieties.

Hydroxycitrate delays early mortality in mice and promotes muscle regeneration while inducing a rich hepatic energetic status.

ATP citrate lyase (ACLY) inhibitors have the potential of modulating central processes in protein, carbohydrate, and lipid metabolism, which can have relevant physiological consequences in aging and age-related diseases. Here, we show that hepatic phospho-active ACLY correlates with overweight and Model for End-stage Liver Disease score in humans. Wild-type mice treated chronically with the ACLY inhibitor potassium hydroxycitrate exhibited delayed early mortality. In AML12 hepatocyte cultures, the ACLY inhibitors potassium hydroxycitrate, SB-204990, and bempedoic acid fostered lipid accumulation, which was also observed in the liver of healthy-fed mice treated with potassium hydroxycitrate. Analysis of soleus tissue indicated that potassium hydroxycitrate produced the modulation of wound healing processes. In vivo, potassium hydroxycitrate modulated locomotor function toward increased wire hang performance and reduced rotarod performance in healthy-fed mice, and improved locomotion in mice exposed to cardiotoxin-induced muscle atrophy. Our findings implicate ACLY and ACLY inhibitors in different aspects of aging and muscle regeneration.

Novel insights into metabolic-associated steatotic liver disease preclinical models.

Metabolic-associated steatotic liver disease (MASLD) encompasses a wide spectrum of metabolic conditions associated with an excess of fat accumulation in the liver, ranging from simple hepatic steatosis to cirrhosis and hepatocellular carcinoma. Finding appropriate tools to study its development and progression is essential to address essential unmet therapeutic and staging needs. This review discusses advantages and shortcomings of different dietary, chemical and genetic factors that can be used to mimic this disease and its progression in mice from a hepatic and metabolic point of view. Also, this review will highlight some additional factors and considerations that could have a strong impact on the outcomes of our model to end up providing recommendations and a checklist to facilitate the selection of the appropriate MASLD preclinical model based on clinical aims.

The antibiotic bead pouch - a useful technique for temporary soft tissue coverage, infection prevention and therapy in trauma surgery.

Soft tissue defects resulting from trauma and musculoskeletal infections can complicate surgical treatment. Appropriate temporary coverage of these defects is essential to achieve the best outcomes for necessary plastic soft tissue defect reconstruction. The antibiotic bead pouch technique is a reasonable surgical approach for managing temporary soft tissue defects following adequate surgical debridement. This technique involves the use of small diameter antibiotic-loaded bone cement beads to fill the dead space created by debridement. By applying antibiotics to the bone cement and covering the beads with an artificial skin graft, high local dosages of antibiotics can be achieved, resulting in the creation of a sterile wound that offers the best starting position for soft tissue and bone defect reconstruction. This narrative review describes the rationale for using this technique, including its advantages and disadvantages, as well as pearls and pitfalls associated with its use in daily practice. In addition, the article provides a comprehensive overview of the literature that has been published since the technique was introduced in surgical practice.

An Alternative Treatment Option for Blauth III B Thumb Hypoplasia-Thumb Stabilization with Iliac Crest Bone Graft and Intermetacarpal Arthrodesis.

Thumb hypoplasia modified Blauth III B is usually treated by pollicization or, less commonly, by toe transfer. Both procedures always result in the resection of a body part, but with good cosmesis and acceptable function. We describe an intermetacarpal I/II arthrodesis with autologous bone graft augmentation to lengthen and stabilize the loose thumb. Clinical data were collected from nine patients, median age at surgery 3 years 8 months, with more than 7 years of follow-up. The results showed a grip strength on the Jamar dynamometer of approximately 61% of the unoperated hand. The Quick-DASH score was 11. The reconstructed thumb was 0.8 cm thinner and 1.9 cm shorter. Overall satisfaction on the VAS, with an average of 1.5 out of 10, is excellent with a partially usable thumb on a hand with five rays. The described procedure is a reliable treatment option with satisfactory results. In addition, none of the patients lost pincer grip between the second and third digit, but their thumb gained new function. Especially in environments where physical integrity has a high value, thumb construction instead of replacement could be considered.

Increased gut permeability and bacterial translocation are associated with fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome: implications for disease-related biomarker discovery.

Background: There is growing evidence of the significance of gastrointestinal complaints in the impairment of the intestinal mucosal barrier function and inflammation in fibromyalgia (FM) and in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, data on intestinal permeability and gut barrier dysfunction in FM and ME/CFS are still limited with conflicting results. This study aimed to assess circulating biomarkers potentially related to intestinal barrier dysfunction and bacterial translocation and their association with self-reported symptoms in these conditions. Methods: A pilot multicenter, cross-sectional cohort study with consecutive enrolment of 22 patients with FM, 30 with ME/CFS and 26 matched healthy controls. Plasma levels of anti-beta-lactoglobulin antibodies (IgG anti-ß-LGB), zonulin-1 (ZO-1), lipopolysaccharides (LPS), soluble CD14 (sCD14) and interleukin-1-beta (IL-1ß) were assayed using ELISA. Demographic and clinical characteristics of the participants were recorded using validated self-reported outcome measures. The diagnostic accuracy of each biomarker was assessed using the receiver operating characteristic (ROC) curve analysis. Results: FM patients had significantly higher levels of anti-ß-LGB, ZO-1, LPS, and sCD14 than healthy controls (all P < 0.0001). In ME/CFS patients, levels of anti-ß-LGB, ZO-1, LPS, and sCD14 were significantly higher than controls, but lower than in FM (all P < 0.01), while there was no significant difference in IL-1ß level. In the FM and ME/CFS cohorts, both anti-ß-LGB and ZO-1 correlated significantly with LPS and sCD14 (P < 0.001 for both). In the FM group, both anti-ß-LGB and ZO-1 were correlated significantly with physical and mental health components on the SF-36 scale (P < 0.05); whereas IL-1ß negatively correlated with the COMPASS-31 score (P < 0.05). In the ME/CFS cohort, ZO-1 was positively correlated with the COMPASS-31 score (P < 0.05). The ROC curve analysis indicated a strong ability of anti-ß-LGB, ZO-1, LPS and sCD14 to predictively distinguish between FM and ME/CFS from healthy controls (P < 0.0001). Conclusion: Biomarkers of intestinal barrier function and inflammation were associated with autonomic dysfunction assessed by COMPASS-31 scores in FM and ME/CFS respectively. Anti-ß-LGB antibodies, ZO-1, LPS, and sCD14 may be putative predictors of intestinal barrier dysfunction in these cohorts. Further studies are needed to assess whether these findings are causal and can therefore be applied in clinical practice.

Missed Essex-Lopresti Injury-Development of a Combined Proximal and Distal Radio-Ulnar Joint Prosthesis as a Treatment Option and Proof of Concept.

Essex-Lopresti injuries are characterized by injuries to the proximal radio-ulnar joint, the distal radio-ulnar joint, and the interosseous membrane. This can lead to osteoarthritis, impaction syndrome, or instability. If all three structures are injured and lead to instability, the situation is almost unmanageable and many times ends in a one-bone forearm. In this article, we demonstrate a new way to reconstruct the proximal and distal radio-ulnar joint with two patient-specific coupled prostheses. These have been developed with the biomechanical conditions of the forearm in mind, where there are very large forces between the bones. As a result, we are able to present a patient previously severely restricted in the use of his hand and arm via a splint that compressed the forearm, who is now able to perform everyday activities and even light sports, such as badminton, without pain.

Three-Loop Technique for Pulley Reconstruction-A Retrospective Cohort Analysis of 23 Patients.

Twenty-three patients with a mean age of 52.7 years underwent pulley reconstruction using the Okutsu double- or triple-loop technique after iatrogenic or traumatic rupture of at least two adjacent flexor tendon pulleys in the finger and distal palm; mean age of injury was 4.77 years. The mean follow-up was 4.66 years after reconstruction of mostly A2 pulleys in a single surgeon setting. Outcome measures included ROM, NRS pain, satisfaction, Disabilities of Arm, Shoulder and Hand Questionnaire (DASH) and Krimmer score, Buck-Gramcko score, Jamar grip strength, pinch grip, and vigorimetry compared to the uninjured side. The median patient satisfaction score was 6.6/10. Hand function using the DASH score was 9.5. Grip strength on the Jamar Dynamometer showed only a slight reduction of 13% compared to the uninjured side. The resultant force of the operated fingers on the vigorimeter is almost 60% of that of the contralateral side, and the finger-palm distance of the operated finger was reduced from 2.2 cm to 1.45 cm. Other functional scores, such as Krimmer (82.2) and Buck-Gramcko (10.9), support these good results. The follow-up of patients more than 4.5 years after reconstruction of the A2 and A3 flexor tendon pulley using the double- or triple-loop technique showed acceptable patient satisfaction and good function of the finger in everyday life.

We are what we eat: The role of lipids in metabolic diseases.

Lipids play a fundamental role, both structurally and functionally, for the correct functioning of the organism. In the last two decades, they have evolved from molecules involved only in energy storage to compounds that play an important role as components of cell membranes and signaling molecules that regulate cell homeostasis. For this reason, their interest as compounds involved in human health has been gaining weight. Indeed, lipids derived from dietary sources and endogenous biosynthesis are relevant for the pathophysiology of numerous diseases. There exist pathological conditions that are characterized by alterations in lipid metabolism. This is particularly true for metabolic diseases, such as liver steatosis, type 2 diabetes, cancer and cardiovascular diseases. The main issue to be considered is lipid homeostasis. A precise control of fat homeostasis is required for a correct regulation of metabolic pathways and safe and efficient energy storage in adipocytes. When this fails, a deregulation occurs in the maintenance of systemic metabolism. This happens because an increased concentrations of lipids impair cellular homeostasis and disrupt tissue function, giving rise to lipotoxicity. Fat accumulation results in many alterations in the physiology of the affected organs, mainly in metabolic tissues. These alterations include the activation of oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, increased inflammation, accumulation of bioactive molecules and modification of gene expression. In this chapter, we review the main metabolic diseases in which alterations in lipid homeostasis are involved and discuss their pathogenic mechanisms.

Metabolic reprogramming by Acly inhibition using SB-204990 alters glucoregulation and modulates molecular mechanisms associated with aging.

ATP-citrate lyase is a central integrator of cellular metabolism in the interface of protein, carbohydrate, and lipid metabolism. The physiological consequences as well as the molecular mechanisms orchestrating the response to long-term pharmacologically induced Acly inhibition are unknown. We report here that the Acly inhibitor SB-204990 improves metabolic health and physical strength in wild-type mice when fed with a high-fat diet, while in mice fed with healthy diet results in metabolic imbalance and moderated insulin resistance. By applying a multiomic approach using untargeted metabolomics, transcriptomics, and proteomics, we determined that, in vivo, SB-204990 plays a role in the regulation of molecular mechanisms associated with aging, such as energy metabolism, mitochondrial function, mTOR signaling, and folate cycle, while global alterations on histone acetylation are absent. Our findings indicate a mechanism for regulating molecular pathways of aging that prevents the development of metabolic abnormalities associated with unhealthy dieting. This strategy might be explored for devising therapeutic approaches to prevent metabolic diseases.

The outcome of boosting mitochondrial activity in alcohol-associated liver disease is organ-dependent.

BACKGROUND AND AIMS: Alcohol-associated liver disease (ALD) accounts for 70% of liver-related deaths in Europe, with no effective approved therapies. Although mitochondrial dysfunction is one of the earliest manifestations of alcohol-induced injury, restoring mitochondrial activity remains a problematic strategy due to oxidative stress. Here, we identify methylation-controlled J protein (MCJ) as a mediator for ALD progression and hypothesize that targeting MCJ may help in recovering mitochondrial fitness without collateral oxidative damage. APPROACH AND RESULTS: C57BL/6 mice [wild-type (Wt)] Mcj knockout and Mcj liver-specific silencing (MCJ-LSS) underwent the NIAAA dietary protocol (Lieber-DeCarli diet containing 5% (vol/vol) ethanol for 10 days, plus a single binge ethanol feeding at day 11). To evaluate the impact of a restored mitochondrial activity in ALD, the liver, gut, and pancreas were characterized, focusing on lipid metabolism, glucose homeostasis, intestinal permeability, and microbiota composition. MCJ, a protein acting as an endogenous negative regulator of mitochondrial respiration, is downregulated in the early stages of ALD and increases with the severity of the disease. Whole-body deficiency of MCJ is detrimental during ALD because it exacerbates the systemic effects of alcohol abuse through altered intestinal permeability, increased endotoxemia, and dysregulation of pancreatic function, which overall worsens liver injury. On the other hand, liver-specific Mcj silencing prevents main ALD hallmarks, that is, mitochondrial dysfunction, steatosis, inflammation, and oxidative stress, as it restores the NAD + /NADH ratio and SIRT1 function, hence preventing de novo lipogenesis and improving lipid oxidation. CONCLUSIONS: Improving mitochondrial respiration by liver-specific Mcj silencing might become a novel therapeutic approach for treating ALD.

Scapholunate ligament reconstruction using a part of the extensor carpi radialis brevis tendon through a dorsal approach.

Thirty-six patients were assessed after scapholunate ligament reconstruction using a portion of the extensor carpi radialis brevis through a dorsal approach. The median age was 53 years. Most (27/38) were graded as scapholunate advanced collapse Grade I. At a median of 47 months after treatment, hand function using the Disabilities of Arm, Shoulder and Hand Questionnaire was 12. The postoperative range of wrist flexion and extension movement was 77% and grip strength 92% compared with the uninjured side. The median patient satisfaction was rated as 9/10. Median pain scores without and with load, using the numeric pain scale (0-10), were 1 and 3, respectively. This reconstruction leads to initial normalization of radiological features, such as scapholunate interval, scapholunate and radiolunate angles, but a notable loss of the immediate postoperative reduction was observed in long-term follow-up, which was not accompanied by any deterioration in the clinical examination. This technique, even in scapholunate advanced collapse type I wrists, resulted in long-term, improved outcomes compared with other techniques.Level of evidence: IV.

[Traumatic spinal cord injuries in sports: a 22-year analysis performed by a specialized trauma centre]. / Traumatische Rückenmarkverletzungen im Sport ­ eine Analyse eines spezialisierten Traumazentrums von 22 Jahren.

INTRODUCTION: There is not much data on traumatic spinal cord injuries sustained during sports in Germany. This study aims to present the frequency of traumatic spinal cord injuries with neurological involvement within various sports over the past 22 years. METHODS: This study is a retrospective evaluation of traumatic spinal cord injuries (tSCI) in sports sustained in the past 22 years. The study was performed by a German level 1 trauma centre with a department for spinal cord injuries. The files of inpatients treated in the years 1998 to 2020 were evaluated with regard to patients' histories and traumatic spinal cord injuries. In addition, injury location and gender distribution were recorded. RESULTS: A total of 1630 patients with traumatic spinal cord injuries with neurological involvement were recorded. Of the 1630 patients, N=116 (7.1%) had had sports accidents. The age of this subpopulation was significantly younger at 41 years (p=0.05) than the age of the total group of tSCI at 50 years. A more detailed analysis of the sports injuries showed that in descending order equestrian sports (N=22), winter (N=18), air (N=16), motor sports (N=16) and cycling (N=15) were the most common causal factors for these particularly serious spinal injuries. As regards the distribution of the location of the spinal cord injury with a view to the type of sports practiced, a significant result was shown in aerial sports, with patients from this group mainly having had lumbar spine injuries (p <0.01), and in diving with cervical spine injuries (p=0). Gender distribution in the individual sports shows a significant difference in equestrian sports (male < female, p <0.01) as well as a significant difference in air sports (male > female, p = 0.05) and cycling (male > female, p=0.07). CONCLUSION: In summary, equestrian sports is the most common cause of spinal cord injuries with neurological involvement in the sports sector with a higher proportion of female participants, although the proportion of female patients is smaller compared with male patients in the section of traumatic spinal cord injuries. Winter (N=18), air (N=16), motor sports (N=15) and cycling (N=15) come next in descending order.Patients with traumatic spinal cord injuries caused by sports accidents are significantly younger than the entirety of patients with traumatic spinal cord injuries.

Derotational osteotomy and internal fixation of a 180° malrotated humerus: A case report.

BACKGROUND: Humeral shaft fractures are relatively common in adults. Rotational malalignment is reported as one complication but severe rotational deformity of the humerus is extremely rare. To our knowledge, only three cases of symptomatic humeral malrotation have been reported. There are sparse literature reports of humeral reconstruction correction. CASE SUMMARY: We present a case of extreme rotational deformity of the humerus (180°) after humeral shaft fracture. The patient complained of pain and difficulties with activities of daily living. In addition, she found the deformity cosmetically unacceptable. Therefore, she was searching for surgical correction. Neurolysis of the radial nerve followed by derotational osteotomy of the humerus and internal fixation were performed. Postoperatively, the patient demonstrated transient iatrogenic radial nerve palsy which recovered completely during postoperative follow-up. The Disabilities of the Arm, Shoulder, and Hand score improved from 55 preoperatively to 16 at the final 2-year follow-up. CONCLUSION: Single-stage radial neurolysis, derotational osteotomy and stable fixation is a feasible option to improve anatomic and functional problems of severely malrotated humeral shaft fractures.

Contribution of Liver and Pancreatic Islet Crosstalk to ß-Cell Function/Dysfunction in the Presence of Fatty Liver.

Tissue-to-tissue crosstalk regulates organ function, according to growing data. This phenomenon is relevant for pancreatic ß-cells and the liver, as both tissues are involved in glucose homeostasis and lipid metabolism. The ability to fine-tune regulation and adaptive responses is enabled through communication between pancreatic ß-cells and the liver. However, the crosstalk between both tissues changes when metabolic dysregulation is present. Factors and cargo from extracellular vesicles (EVs) released by liver and pancreatic ß-cells that reach the circulation form the words of this interaction. The molecules released by the liver are called hepatokines and are usually secreted in response to the metabolic state. When hepatokines reach the pancreatic islets several mechanisms are initiated for their protection or damage. In the case of the crosstalk between pancreatic ß-cells and the liver, only one factor has been found to date. This protein, pancreatic derived factor (PANDER) has been proposed as a novel linker between insulin resistance (IR) and type 2 diabetes mellitus (T2D) and could be considered a biomarker for non-alcoholic fatty liver disease (NAFLD) and T2D. Furthermore, the cargo released by EVs, mainly miRNAs, plays a significant role in this crosstalk. A better knowledge of the crosstalk between liver and pancreatic ß-cells is essential to understand both diseases and it could lead to better prevention and new therapeutic options.

NR5A2/LRH-1 regulates the PTGS2-PGE2-PTGER1 pathway contributing to pancreatic islet survival and function.

LRH-1/NR5A2 is implicated in islet morphogenesis postnatally, and its activation using the agonist BL001 protects islets against apoptosis, reverting hyperglycemia in mouse models of Type 1 Diabetes Mellitus. Islet transcriptome profiling revealed that the expression of PTGS2/COX2 is increased by BL001. Herein, we sought to define the role of LRH-1 in postnatal islet morphogenesis and chart the BL001 mode of action conferring beta cell protection. LRH-1 ablation within developing beta cells impeded beta cell proliferation, correlating with mouse growth retardation, weight loss, and hypoglycemia leading to lethality. LRH-1 deletion in adult beta cells abolished the BL001 antidiabetic action, correlating with beta cell destruction and blunted Ptgs2 induction. Islet PTGS2 inactivation led to reduced PGE2 levels and loss of BL001 protection against cytokines as evidenced by increased cytochrome c release and cleaved-PARP. The PTGER1 antagonist-ONO-8130-negated BL001-mediated islet survival. Our results define the LRH-1/PTGS2/PGE2/PTGER1 signaling axis as a key pathway mediating BL001 survival properties.

Effect of Acute Intake of Fermented Orange Juice on Fasting and Postprandial Glucose Metabolism, Plasma Lipids and Antioxidant Status in Healthy Human.

Higher postprandial plasma glucose and lipemia, and oxidative and inflammatory responses, are considered important cardiovascular risk factors. Fermentation of fruits has generated products with high concentrations of bioactive compounds. The aim of this study was to evaluate the potential acute effects that fermented orange juice (FOJ) can exert in healthy humans by modulating postprandial response, and inflammatory/antioxidant status, compared with orange juice (OJ). Nine volunteers were recruited for a randomized, controlled, and crossover study. Participants ingested 500 mL of FOJ. At 4 h post intake, subjects consumed a standardized mixed meal. Blood samples were collected at 0-8 h hours post intake. The subjects repeated the protocol with OJ following a 2-week washout period. Glucose and lipid metabolism, plasma antioxidant capacity (ORAC, FRAP), endogenous antioxidants (albumin, bilirubin, uric acid), C-reactive protein and fibrinogen were measured in plasma samples. There was a trend of a smaller increase in LDL-C after FOJ intake compared with OJ, a significant decrease in apo-B and significant increase in ORAC. The glycemic and triglyceride response of meal was attenuated with FOJ. No differences were obtained in endogenous antioxidants and inflammation status between the treatments. The acute consumption of FOJ could play a protective role against cardiovascular risk factors.

Pdx1 Is Transcriptionally Regulated by EGR-1 during Nitric Oxide-Induced Endoderm Differentiation of Mouse Embryonic Stem Cells.

The transcription factor, early growth response-1 (EGR-1), is involved in the regulation of cell differentiation, proliferation, and apoptosis in response to different stimuli. EGR-1 is described to be involved in pancreatic endoderm differentiation, but the regulatory mechanisms controlling its action are not fully elucidated. Our previous investigation reported that exposure of mouse embryonic stem cells (mESCs) to the chemical nitric oxide (NO) donor diethylenetriamine nitric oxide adduct (DETA-NO) induces the expression of early differentiation genes such as pancreatic and duodenal homeobox 1 (Pdx1). We have also evidenced that Pdx1 expression is associated with the release of polycomb repressive complex 2 (PRC2) and P300 from the Pdx1 promoter; these events were accompanied by epigenetic changes to histones and site-specific changes in the DNA methylation. Here, we investigate the role of EGR-1 on Pdx1 regulation in mESCs. This study reveals that EGR-1 plays a negative role in Pdx1 expression and shows that the binding capacity of EGR-1 to the Pdx1 promoter depends on the methylation level of its DNA binding site and its acetylation state. These results suggest that targeting EGR-1 at early differentiation stages might be relevant for directing pluripotent cells into Pdx1-dependent cell lineages.