A phase I, first-in-human study to evaluate the safety and tolerability, pharmacokinetics, and pharmacodynamics of MRG-001 in healthy subjects.

Preclinical studies demonstrate that pharmacological mobilization and recruitment of endogenous bone marrow stem cells and immunoregulatory cells by a fixed-dose drug combination (MRG-001) improves wound healing, promotes tissue regeneration, and prevents allograft rejection. In this phase I, first-in-human study, three cohorts receive subcutaneous MRG-001 or placebo, every other day for 5 days. The primary outcome is safety and tolerability of MRG-001.

Loss of hepatic DRP1 exacerbates alcoholic hepatitis by inducing megamitochondria and mitochondrial maladaptation.

Background And Aims: Increased megamitochondria formation and impaired mitophagy in hepatocytes have been linked to the pathogenesis of alcohol-associated liver disease (ALD). This study aims to determine the mechanisms by which alcohol consumption increases megamitochondria formation in the pathogenesis of ALD.

Approach And Results: Human alcoholic hepatitis (AH) liver samples were used for electron microscopy, histology, and biochemical analysis.

Proteomic analysis of alcohol-associated hepatitis reveals glycoprotein NMB (GPNMB) as a novel hepatic and serum biomarker.

Alcohol consumption remains a leading cause of liver disease worldwide, resulting in a complex array of hepatic pathologies, including steatosis, steatohepatitis, and cirrhosis. Individuals who progress to a rarer form of alcohol-associated liver disease (ALD), alcohol-associated hepatitis (AH), require immediate life-saving intervention in the form of liver transplantation. Rapid onset of AH is poorly understood and the metabolic mechanisms contributing to the progression to liver failure remain undetermined.

The never-ending battle between proximal row carpectomy and four corner arthrodesis: A systematic review and meta-analysis for the final verdict.

While scaphoid excision combined with Four Corner Arthrodesis (FCA) or Proximal Row Carpectomy (PRC) is a commonly-used salvage procedures to treat type two and type three Scapholunate Advanced Collapse (SLAC) and Scaphoid Nonunion Advanced Collapse (SNAC)-induced degenerative arthritis, controversy remains over which treatment intervention provides superior outcomes. We searched for articles comparing a range of motion, grip strength, complications requiring reoperation, conversion to wrist arthrodesis, pain, and disability of shoulder and arm scores between FCA and PRC-treated patients. The risk of bias was assessed using the National Institutes of Health (NIH) quality assessment tool.

Combination of Autologous Fat Grafting and Negative-Pressure Wound Therapy for the Treatment of Scalp Linear Scleroderma.

Scalp linear scleroderma (LSc) is a subtype of localized scleroderma which typically affects young patients and which can be severely disfiguring. Traditional treatment options include bone grafting or tissue expansion. in this report, we present the case of a patient with scalp LSc successfully treated with scar release, autologous fat grafting, and negative-pressure wound therapy (NPWT).

A case series of pulmonary hypertension in small infants with atrial septal defect.

Background: Atrial septal defect (ASD) is one of the most common congenital heart defects (CHDs) with prevalence of 8% to 10% in children with CHD and incidence of 56 per 100000 live births. It is categorized according to the defect site in which the most common form is secundum ASD (ASD2) with the defect in the central part of the atrial septum.

Case Report: In our case series, we evaluated five children aged under one year old with ASD2 and pulmonary hypertension (PH).

Systematic Review and Meta-Analysis of Complications Following Mastectomy and Prosthetic Reconstruction in Patients With and Without Prior Breast Augmentation.

Background: There is limited evidence available in the literature with regard to the complication profile of mastectomy and immediate prosthetic reconstruction in augmented patients.

Objectives: The aim of this systematic review and meta-analysis was to compare postoperative complications between women with vs without prior augmentation undergoing skin- or nipple-sparing mastectomy and immediate prosthetic reconstruction.

Methods: A systematic search was conducted in February 2020 for studies comparing women with vs without prior augmentation undergoing skin- or nipple-sparing mastectomy and immediate prosthetic reconstruction with documentation of postoperative complications.

ATF4 activation promotes hepatic mitochondrial dysfunction by repressing NRF1-TFAM signalling in alcoholic steatohepatitis.

Objective: Mitochondrial dysfunction plays a dominant role in the pathogenesis of alcoholic liver disease (ALD); however, the underlying mechanisms remain to be fully understood. We previously found that hepatic activating transcription factor 4 (ATF4) activation was associated with mitochondrial dysfunction in ALD. This study aimed to investigate the function and mechanism of ATF4 in alcohol-induced hepatic mitochondrial dysfunction.

Rifampicin for Treatment of Cholestatic Pruritus Caused by Drug-Induced Acute Liver Injury as Assessed by the RUCAM Classification.

A male bodybuilder of 39 years of age developed severe pruritus, nausea, and jaundice after injecting anabolic steroids purchased on the black market. The patient had no history of liver disease and no risk factors for viral hepatitis. Extensive laboratory testing, radiographic imaging, and liver biopsy excluded a majority of potential pathologies.

Major Improvement in Wound Healing Through Pharmacologic Mobilization of Stem Cells in Severely Diabetic Rats.

Current therapeutic strategies for diabetic foot ulcer (DFU) have focused on developing topical healing agents, but few agents have controlled prospective data to support their effectiveness in promoting wound healing. We tested a stem cell mobilizing therapy for DFU using a combination of AMD3100 and low-dose FK506 (tacrolimus) (AF) in streptozocin-induced type 1 diabetic (T1DM) rats and type 2 diabetic Goto-Kakizaki (GK) rats that had developed peripheral artery disease and neuropathy. Here, we show that the time for healing back wounds in T1DM rats was reduced from 27 to 19 days, and the foot wound healing time was reduced from 25 to 20 days by treatment with AF (subcutaneously, every other day).

Epithelial splicing regulatory protein 2-mediated alternative splicing reprograms hepatocytes in severe alcoholic hepatitis.

Severe alcoholic hepatitis (SAH) is a deadly liver disease without an effective medical therapy. Although SAH mortality is known to correlate with hepatic accumulation of immature liver cells, why this occurs and how it causes death are unclear. Here, we demonstrate that expression of epithelial splicing regulatory protein 2 (ESRP2), an RNA-splicing factor that maintains the nonproliferative, mature phenotype of adult hepatocytes, was suppressed in both human SAH and various mouse models of SAH in parallel with the severity of alcohol consumption and liver damage.

Paneth Cell Dysfunction Mediates Alcohol-related Steatohepatitis Through Promoting Bacterial Translocation in Mice: Role of Zinc Deficiency.

Background And Aims: Microbial dysbiosis is associated with alcohol-related hepatitis (AH), with the mechanisms yet to be elucidated. The present study aimed to determine the effects of alcohol and zinc deficiency on Paneth cell (PC) antimicrobial peptides, α-defensins, and to define the link between PC dysfunction and AH.

Approach And Results: Translocation of pathogen-associated molecular patterns (PAMPs) was determined in patients with severe AH and in a mouse model of alcoholic steatohepatitis.

The efficacy and safety of using amplatzer for transcatheter closure of atrial septal defect in small children with less than 10 kg.

Background: Atrial septal defect (ASD) accounts for about 10% of congenital heart diseases (CHDs). Self-closure of these defects in patients with defects less than 8 mm has been reported in several studies. In children, transcatheter closure of the ASD is suggested for asymptomatic patients older than two years and with weight > 15 kg.

The epigenetic regulator SIRT6 protects the liver from alcohol-induced tissue injury by reducing oxidative stress in mice.

Background & Aims: As a nicotinamide adenine dinucleotide-dependent deacetylase and a key epigenetic regulator, sirtuin 6 (SIRT6) has been implicated in the regulation of metabolism, DNA repair, and inflammation. However, the role of SIRT6 in alcohol-related liver disease (ALD) remains unclear. The aim of this study was to investigate the function and mechanism of SIRT6 in ALD pathogenesis.

Midterm Follow-up Results of Transcatheter Interatrial Septal Defect Closure.

Objectives: We studied immediate and midterm results of transcatheter closure of atrial septal defects (ASDs) using the Amplatzer septal device closure.

Methods: The study included one hundred and thirty-seven patients (31 men, 106 women; mean age 8 ± 7.3 years; range 1-65 years) who underwent transcatheter closure of secundum ASD between October 2014 and October 2016 in our center.

Orthotopic Rat Kidney Transplantation: A Novel and Simplified Surgical Approach.

Kidney transplantation offers increased survival rates and improved quality of life for patients with end-stage renal disease, as compared to any type of renal replacement therapy. Over the past few decades, the rat kidney transplantation model has been used to study the immunological phenomena of rejection and tolerance. This model has become an indispensable tool to test new immunomodulatory pharmaceuticals and regimens prior to proceeding with expensive preclinical large animal studies.

Phosphodiesterase 4 Inhibition as a Therapeutic Target for Alcoholic Liver Disease: From Bedside to Bench.

Alcoholic liver disease (ALD) is a major cause of liver-related mortality. There is still no US Food and Drug Administration-approved therapy for ALD, and therefore, identifying therapeutic targets is needed. Our previous work demonstrated that ethanol exposure leads to up-regulation of cAMP-degrading phosphodiesterase 4 (PDE4) expression, which compromises normal cAMP signaling in monocytes/macrophages and hepatocytes.

Pharmacological Mobilization and Recruitment of Stem Cells in Rats Stops Abdominal Adhesions After Laparotomy.

Adhesions are a very common complication in the abdominal surgery. Animal studies and human trials have evaluated strategies designed to reduce and prevent postsurgical adhesions but few have an evidence base that justifies routine use. A strategy to prevent adhesions effectively remains an urgent need.

Activation of BMP Signaling by FKBP12 Ligands Synergizes with Inhibition of CXCR4 to Accelerate Wound Healing.

The combination of AMD3100 and low-dose FK506 has been shown to accelerate wound healing in vivo. Although AMD3100 is known to work by releasing hematopoietic stem cells into circulation, the mechanism of FK506 in this setting has remained unknown. In this study, we investigated the activities of FK506 in human cells and a diabetic-rat wound model using a non-immunosuppressive FK506 analog named FKVP.

Association between NOS3 and 4a/4b Variants and Coronary Artery Diseases in Iranian Population.

Background: Endothelial nitric oxide synthase, encoded by , produces an atheroprotective metabolite. The and 4a/4b variants of this gene associated with increased risk for coronary artery diseases (CAD) have been evaluated in different populations worldwide, and inconsistent results have been obtained. We investigated the association between these three polymorphisms and presence of CAD in Iranian individuals.