Wounds are among the most common skin conditions, displaying a large etiological diversity and being characterized by different degrees of severity. Wound healing is a complex process that involves multiple steps such as inflammation, proliferation and maturation and ends with scar formation. Since ancient times, a widely used option for treating skin wounds are plant- based treatments which currently have become the subject of modern pharmaceutical formulations. Triterpenes with tetracyclic and pentacyclic structure are extensively studied for their implication in wound healing as well as to determine their molecular mechanisms of action. The current review aims to summarize the main results of in vitro, in vivo and clinical studies conducted on lupane, ursane, oleanane, dammarane, lanostane and cycloartane type triterpenes as potential wound healing treatments.

The aim of this article is to show how thevpower of statistics and cheminformatics can be combined, in R, using two packages: rcdk and cluster.We describe the role of clustering methods for identifying similar structures in a group of 23 molecules according to their fingerprints. The most commonly used method is to group the molecules using a “score” obtained by measuring the average distance between them. This score reflects the similarity/non-similarity between compounds and helps us identify active or potentially toxic substances through predictive studies.Clustering is the process by which the common characteristics of a particular class of compounds are identified. For clustering applications, we are generally measure the molecular fingerprint similarity with the Tanimoto coefficient. Based on the molecular fingerprints, we calculated the molecular distances between the methotrexate molecule and the other 23 molecules in the group, and organized them into a matrix. According to the molecular distances and Ward ’s method, the molecules were grouped into 3 clusters. We can presume structural similarity between the compounds and their locations in the cluster map. Because only 5 molecules were included in the methotrexate cluster, we considered that they might have similar properties and might be further tested as potential drug candidates.

Triterpenic acids are a widespread class of phytocompounds which have been found to possess valuable therapeutic properties such as anticancer, anti-inflammatory, hepatoprotective, cardioprotective, antidiabetic, neuroprotective, lipolytic, antiviral, and antiparasitic effects. They are a subclass of triterpenes bearing a characteristic lipophilic structure that imprints unfavorable in vivo properties which subsequently limit their applications. The early investigation of the mechanism of action (MOA) of a drug candidate can provide valuable information regarding the possible side effects and drug interactions that may occur after administration. The current paper aimed to summarize the most recent (last 5 years) studies regarding the MOA of betulinic acid, boswellic acid, glycyrrhetinic acid, madecassic acid, moronic acid, and pomolic acid in order to provide scientists with updated and accessible material on the topic that could contribute to the development of future studies; the paper stands as the sequel of our previously published paper regarding the MOA of triterpenic acids with therapeutic value. The recent literature published on the topic has highlighted the role of triterpenic acids in several signaling pathways including PI3/AKT/mTOR, TNF-alpha/NF-kappa B, JNK-p38, HIF-α/AMPK, and Grb2/Sos/Ras/MAPK, which trigger their various biological activities.

Betulinic acid (BA) was demonstrated to be a very promising anticancer agent against various tumor cell lines such as breast, colon, lung, and brain. Despite its strong cytotoxic effect, betulinic acid exhibits low water solubility, feature that is reflected in its poor bioavailability. To overcome these drawbacks, numerous strategies were conducted to improve its physicochemical and pharmacokinetic profile, among which cocrystalization emerged as a promising approach. Thus, our work consisted in obtaining slowly grown cocrystals of BA and ascorbic acid (BA+VitC) in isopropyl alcohol obtained in a hydrothermal experiment. The newly formed cocrystals were characterized by physico-chemical methods such asSEM, DSC, XRPD, and FT-IR spectroscopy demonstrating BA+VitC cocrystal formation while their antioxidant activity revealed an additive antioxidant effect. To investigate the biological effect, BA+VitC cocrystals were tested on HaCat (immortalized human keratinocytes), B164A5 and B16F0 (murine melanoma), MCF7 and MDA-MB-231 (human breast cancer), and HeLa (cervical cancer) cell lines. Results of BA upon the tested tumor cell lines, after co-crystallization with vitamin C, indicated a superior cytotoxic effect with the preservation of a good selectivity index assumably due to an improved BA water solubility and consequently an optimized bioavailability.

Due to the vulnerable nature of its patients, the wide use of invasive devices and broad-spectrum antimicrobials used, the intensive care unit (ICU) is often called the epicentre of infections. In the present study, we quantified the burden of hospital acquired pathology in a Romanian university hospital ICU, represented by antimicrobial agents consumption, costs and local resistance patterns, in order to identify multimodal interventional strategies. Between 1st January 2012 and 31st December 2013, a prospective study was conducted in the largest ICU of Western Romania. The study group was divided into four sub-samples: patients who only received prophylactic antibiotherapy, those with community-acquired infections, patients who developed hospital acquired infections and patients with community acquired infections complicated by hospital-acquired infections. The statistical analysis was performed using the EpiInfo version 3.5.4 and SPSS version 20. A total of 1596 subjects were enrolled in the study and the recorded consumption of antimicrobial agents was 1172.40 DDD/ 1000 patient-days. The presence of hospital acquired infections doubled the length of stay (6.70 days for patients with community-acquired infections versus 16.06/14.08 days for those with hospital-acquired infections), the number of antimicrobial treatment days (5.47 in sub-sample II versus 11.18/12.13 in sub-samples III/IV) and they increased by 4 times compared to uninfected patients. The perioperative prophylactic antibiotic treatment had an average length duration of 2.78 while the empirical antimicrobial therapy was 3.96 days in sample II and 4.75/4.85 days for the patients with hospital-acquired infections. The incidence density of resistant strains was 8.27/1000 patient-days for methicilin resistant Staphylococcus aureus, 7.88 for extended spectrum β-lactamase producing Klebsiella pneumoniae and 4.68/1000 patient-days for multidrug resistant Acinetobacter baumannii. Some of the most important circumstances collectively contributing to increasing the consumption of antimicrobials and high incidence densities of multidrug-resistant bacteria in the studied ICU, are represented by prolonged chemoprophylaxis and empirical treatment and also by not applying the definitive antimicrobial therapy, especially in patients with favourable evolution under empirical antibiotic treatment. The present data should represent convincing evidence for policy changes in the antibiotic therapy.

Over the past two decades, the use of tumor necrosis factor alpha (TNF-α) inhibitors has significantly improved the treatment of patients with immune-mediated inflammatory diseases. Firstly, introduced for rheumatoid arthritis, these inhibitors are currently approved and used for a variety of conditions, including ankylosing spondylitis, Crohn’s disease, juvenile idiopathic arthritis, psoriasis, psoriatic arthritis, ulcerative colitis, and chronic uveitis. Despite their immense therapeutic efficacy, TNF-α inhibitors have been associated with neurological adverse effects that bring new clinical challenges. The present review collects data from multiple studies to evaluate the incidence and the relationship between TNF-α inhibitors and neurological side effects and to explore the potential underlying mechanisms of this association. Moreover, it highlights the importance of patient selection, particularly in the case of individuals with a history of demyelinating diseases, raises awareness for clinicians, and calls for ongoing research that will improve TNF-α targeting strategies and offer safer and more effective therapeutic options.