The Efficacy of Metformin as a Therapeutic Agent in the Treatment of Acne Vulgaris: A Systematic Review.

A large portion of the world's population is affected by acne vulgaris (AV), with many of these individuals being adolescents. The underlying mechanism of AV is hyperkeratinization and Cutibacterium acnes infection of the pilosebaceous follicle secondary to excessive stimulation of sebaceous glands by androgens. Metformin is a biguanide medication primarily used in efforts to lower patients' sugar levels in the management of type 2 diabetes. It has been proven to reduce levels of circulating androgens in patients with insulin resistance, indicating its potential for treating AV. A search strategy was developed and performed using the databases Ovid Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Controlled Register of Trials (CENTRAL), and Web of Science. The keywords "metformin" and "acne" were searched, along with related Medical Subject Headings (MeSH) and other subject headings. Studies that met the inclusion criteria were controlled trials, published after 2010, and in the English language. Participants with and without comorbidities such as polycystic ovary syndrome (PCOS) were considered. Two independent reviewers screened studies based on predefined criteria and extracted data from each study, which were quantitatively combined. A total of 15 studies were included in this systematic review. Across the 15 studies, there were 1,046 participants, with 13 studies looking exclusively at women with PCOS. Of the remaining two studies, one examined males with altered metabolic profiles, while the other included men and women with moderate AV. Notable risks of bias included studies that did not exclusively state the blindness of the study. Of the studies that were examined, 13 showed that metformin reduces AV, with seven studies showing statistical significance. Acne vulgaris is an inflammatory condition that has plagued patients for years due to the limited treatment options available. The hyperglycemic medication metformin, used in the management of type 2 diabetes, is being explored as a novel therapeutic that can possibly be repurposed for the treatment of AV. The use of metformin in AV is hypothesized to disrupt the proposed linkage between insulin resistance and AV proliferation. This proposed research could offer physicians a new option for the treatment of AV as well as render an alternative AV treatment for patients.

Differential Biological Effects of Dietary Lipids and Irradiation on the Aorta, Aortic Valve, and the Mitral Valve.

Aims: Dietary cholesterol and palmitic acid are risk factors for cardiovascular diseases (CVDs) affecting the arteries and the heart valves. The ionizing radiation that is frequently used as an anticancer treatment promotes CVD. The specific pathophysiology of these distinct disease manifestations is poorly understood. We, therefore, studied the biological effects of these dietary lipids and their cardiac irradiation on the arteries and the heart valves in the rabbit models of CVD. Methods and Results: Cholesterol-enriched diet led to the thickening of the aortic wall and the aortic valve leaflets, immune cell infiltration in the aorta, mitral and aortic valves, as well as aortic valve calcification. Numerous cells expressing α-smooth muscle actin were detected in both the mitral and aortic valves. Lard-enriched diet induced massive aorta and aortic valve calcification, with no detectable immune cell infiltration. The addition of cardiac irradiation to the cholesterol diet yielded more calcification and more immune cell infiltrates in the atheroma and the aortic valve than cholesterol alone. RNA sequencing (RNAseq) analyses of aorta and heart valves revealed that a cholesterol-enriched diet mainly triggered inflammation-related biological processes in the aorta, aortic and mitral valves, which was further enhanced by cardiac irradiation. Lard-enriched diet rather affected calcification- and muscle-related processes in the aorta and aortic valve, respectively. Neutrophil count and systemic levels of platelet factor 4 and ent-8-iso-15(S)-PGF2α were identified as early biomarkers of cholesterol-induced tissue alterations, while cardiac irradiation resulted in elevated levels of circulating nucleosomes. Conclusion: Dietary cholesterol, palmitic acid, and cardiac irradiation combined with a cholesterol-rich diet led to the development of distinct vascular and valvular lesions and changes in the circulating biomarkers. Hence, our study highlights unprecedented specificities related to common risk factors that underlie CVD.

Exercise echocardiography in aortic stenosis with preserved ejection fraction.

The appropriate timing of intervention and follow-up in asymptomatic patients with aortic stenosis remains controversial. Risk stratification is a key, especially with the use of a multimodality imaging approach, including exercise stress echocardiography. This review focuses on the use of exercise echocardiography in asymptomatic patients with moderate and severe aortic stenosis with preserved left ventricular ejection fraction. It describes the exercise echocardiography protocol, parameters to be evaluated, and its role in guiding the timing of intervention and follow-up in these patients.

Dexfenfluramine and Pergolide Cause Heart Valve Disease via Valve Metabolic Reprogramming and Ongoing Matrix Remodeling.

Several clinical reports indicate that the use of amphetaminic anorectic drugs or ergot derivatives could cause valvular heart disease (VHD). We sought to investigate whether valvular lesions develop in response to long-term oral administration of these drugs and to identify drug-targeted biological processes that may lead to VHD. Treatment of New Zealand White rabbits with pergolide, dexfenfluramine, or high-dose serotonin for 16 weeks induced valvular alterations characterized by extracellular matrix remodeling. Transcriptome profiling of tricuspid valves using RNA sequencing revealed distinct patterns of differentially expressed genes (DEGs) that clustered according to the different treatments. Genes that were affected by the three treatments were functionally enriched for reduced cell metabolism processes. The two drugs yielded more changes in gene expression than serotonin and shared most of the DEGs. These DEGs were mostly enriched for decreased biosynthetic processes, increased cell-matrix interaction, and cell response to growth factors, including TGF-ß, which was associated with p38 MAPK activation. Treatment with pergolide specifically affected genes involved in homeostasis, which was corroborated by the activation of the master regulator of cell energy homeostasis, AMPK-α, as well as decreased levels of metabolism-related miR-107. Thus, both pergolide and dexfenfluramine may cause VHD through valve metabolic reprogramming and matrix remodeling.

Neutrophil Phenotypes in Coronary Artery Disease.

Clinical evidence indicates that innate immune cells may contribute to acute coronary syndrome (ACS). Our prospective study aimed at investigating the association of neutrophil phenotypes with ACS. 108 patients were categorized into chronic stable coronary artery disease (n = 37), unstable angina (UA) (n = 19), Non-ST-Elevation Myocardial Infarction (NSTEMI) (n = 25), and ST-Elevation Myocardial Infarction (STEMI) (n = 27). At the time of inclusion, blood neutrophil subpopulations were analysed by flow cytometry. Differential blood cell count and plasma levels of neutrophilic soluble markers were recorded at admission and, for half of patients, at six-month follow-up. STEMI and NSTEMI patients displayed higher neutrophil count and neutrophil-to-lymphocyte ratio than stable and UA patients (p < 0.0001), which normalized at six-month post-MI. Atypical low-density neutrophils were detected in the blood of the four patient groups. STEMI patients were characterized by elevated percentages of band cells compared to the other patients (p = 0.019). Multivariable logistic regression analysis revealed that plasma levels of total myeloperoxidase was associated with STEMI compared to stable (OR: 1.434; 95% CI: 1.119-1.837; P < 0.0001), UA (1.47; 1.146-1.886; p = 0.002), and NSTEMI (1.213; 1.1-1.134; p = 0.0001) patients, while increased neutrophil side scatter (SSC) signal intensity was associated with NSTEMI compared to stable patients (3.828; 1.033-14.184; p = 0.045). Hence, changes in neutrophil phenotype are concomitant to ACS.

Global and regional myocardial function and outcomes after transcatheter aortic valve implantation for aortic stenosis and preserved ejection fraction.

AIM: To investigate the effects of transcatheter aortic valve implantation (TAVI) on early recovery of global and segmental myocardial function in patients with severe symptomatic aortic stenosis and preserved left ventricular ejection fraction (LVEF) and to determine if parameters of deformation correlate with outcomes. METHODS: The echocardiographic (strain analysis) and outcome (hospitalizations because of heart failure and mortality) data of 62 consecutive patients with preserved LVEF (64.54 ±â€Š7.97%) who underwent CoreValve prosthesis implantation were examined. RESULTS: Early after TAVI (5 ±â€Š3.9 days), no significant changes in LVEF or diastolic function were found, while a significant drop of systolic pulmonary artery pressure (PAP) occurred (42.3 ±â€Š14.9 vs. 38.1 ±â€Š13.9 mmHg, P = 0.028). After TAVI global longitudinal strain (GLS) did not change significantly, whereas significant improvement in global mid-level left ventricular (LV) radial strain (GRS) was found (-16.71 ±â€Š2.42 vs. -17.32 ±â€Š3.25%; P = 0.33; 16.57 ±â€Š6.6 vs. 19.48 ±â€Š5.97%, P = 0.018, respectively). Early significant recovery of longitudinal strain was found in basal lateral and anteroseptal segments (P = 0.038 and 0.048). Regional radial strain at the level of papillary muscles [P = 0.038 mid-lateral, P < 0.001 mid-anteroseptum (RSAS)] also improved. There was a significant LV mass index reduction in the late follow-up (152.42 ±â€Š53.21 vs. 136.24 ±â€Š56.67 g/m, P = 0.04). Mean follow-up period was 3.5 ±â€Š1.9 years. Parameters associated with worse outcomes in univariable analysis were RSAS pre-TAVI, LV end-diastolic diameter after TAVI, relative wall thickness, and mitral E and E/A after TAVI. CONCLUSION: Global and regional indices of myocardial function improved early after TAVI, suggesting the potential of myocardium to recover with a reduced risk for clinical deterioration.

Synthetic combinations of missense polymorphic genetic changes underlying Down syndrome susceptibility.

Single nucleotide polymorphisms (SNPs) are important biomolecular markers in health and disease. Down syndrome, or Trisomy 21, is the most frequently occurring chromosomal abnormality in live-born children. Here, we highlight associations between SNPs in several important enzymes involved in the one-carbon folate metabolic pathway and the elevated maternal risk of having a child with Down syndrome. Our survey highlights that the combination of SNPs may be a more reliable predictor of the Down syndrome phenotype than single SNPs alone. We also describe recent links between SNPs in p53 and its related pathway proteins and Down syndrome, as well as highlight several proteins that help to associate apoptosis and p53 signaling with the Down syndrome phenotype. In addition to a comprehensive review of the literature, we also demonstrate that several SNPs reside within the same regions as these Down syndrome-linked SNPs, and propose that these closely located nucleotide changes may provide new candidates for future exploration.