Nicotinamide Mononucleotide (NMN) Works in Type 2 Diabetes through Unexpected Effects in Adipose Tissue, Not by Mitochondrial Biogenesis.

Nicotinamide mononucleotide (NMN) has emerged as a promising therapeutic intervention for age-related disorders, including type 2 diabetes. In this study, we confirmed the previously observed effects of NMN treatment on glucose uptake and investigated its underlying mechanisms in various tissues and cell lines. Through the most comprehensive proteomic analysis to date, we discovered a series of novel organ-specific effects responsible for glucose uptake as measured by the IPGTT: adipose tissue growing (suggested by increased protein synthesis and degradation and mTOR proliferation signaling upregulation). Notably, we observed the upregulation of thermogenic UCP1, promoting enhanced glucose conversion to heat in intermuscular adipose tissue while showing a surprising repressive effect on mitochondrial biogenesis in muscle and the brain. Additionally, liver and muscle cells displayed a unique response, characterized by spliceosome downregulation and concurrent upregulation of chaperones, proteasomes, and ribosomes, leading to mildly impaired and energy-inefficient protein synthesis machinery. Furthermore, our findings revealed remarkable metabolic rewiring in the brain. This involved increased production of ketone bodies, downregulation of mitochondrial OXPHOS and TCA cycle components, as well as the induction of well-known fasting-associated effects. Collectively, our data elucidate the multifaceted nature of NMN action, highlighting its organ-specific effects and their role in improving glucose uptake. These findings deepen our understanding of NMN's therapeutic potential and pave the way for novel strategies in managing metabolic disorders.

Identification of Uric Acid Crystals Accumulation in Human and Animal Tissues Using Combined Morphological and Raman Spectroscopy Analysis.

Gout is a metabolic condition, common to animals and humans, issuing from the excessive accumulation of end products of proteins degradation. In this study, histopathological and cytological examinations, combined with Raman spectroscopy, have been performed to investigate tissue samples from reptiles, chickens, and humans, presenting lesions produced by uric acid accumulation. As a result of classic processing and staining techniques commonly used in the anatomopathological diagnosis, uric acid crystals lose their structural characteristics, thus making difficult a precise diagnostic. Therefore, complementary diagnostic methods, such as Raman spectroscopy, are needed. This study compares from several perspectives the above mentioned diagnostic methods, concluding that Raman spectroscopy provides highlights in the diagnosis of gout in humans and animals, also adding useful information to differential diagnosis of lesions.

TiO2 Nanotubes Functionalized with Icariin for an Attenuated In Vitro Immune Response and Improved In Vivo Osseointegration.

Due to their superior mechanical and chemical properties, titanium (Ti) and its alloys have been widely used as orthopedic implantable devices. However, their bioinertness represents a limitation, which can be overcome by employing various surface modifications, such as TiO2 nanotube (TNT) fabrication via electrochemical anodization. Anodic TNTs present tunable dimensions and unique structures, turning them into feasible drug delivery platforms. In the present work, TNTs were loaded with icariin (Ica) through an adhesive intermediate layer of polydopamine (DP), and their in vitro and in vivo biological performance was evaluated. The successful fabrication of the modified surfaces was verified by scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), and contact angle measurements (CA), while the in vitro release of Ica was evaluated via UV-VIS spectrophotometry. In terms of in vitro behaviour, comparative studies on RAW 264.7 macrophages demonstrated that the TNT substrates, especially TNT-DP-Ica, elicited a lower inflammatory response compared to the Ti support. Moreover, the in vivo implantation studies evinced generation of a reduced fibrotic capsule around this implant and increased thickness of the newly formed bone tissue at 1 month and 3 months post-implantation, respectively. Overall, our results indicate that the controlled release of Ica from TNT surfaces could result in an improved osseointegration process.

Meropenem antibiotic therapy in acute secondary peritonitis, therapeutic effects superior to other therapies - experimental clinical and histopathological study in the laboratory animal.

AIM: A perforated peptic ulcer is the most common cause of peritonitis through the perforation of the digestive tube, which occurs in a percentage between 2% and 14% of patients diagnosed with peptic ulcer and being associated with a 10% to 30% mortality rate. MATERIALS AND METHODS: Considering the above, we imagined a study, using laboratory animals, in which we produced gastric perforations, then followed their evolution without antibiotic treatment and under antibiotic therapy with Cefuroxime 25 mg∕kg∕24 hours intravenously or Meropenem 40 mg∕kg∕24 hours intravenously, following the tissue changes both macroscopically and microscopically. RESULTS: The study revealed a mortality of 36.6%, most deaths (81.82%) occurred in the first 24 hours after the perforation, all subjects belonging to the group that did not receive antibiotic treatment and the group treated with Cefuroxime. From a clinical point of view (evaluation of the general condition), macroscopically and microscopically, a better evolution of the subjects who received antibiotic therapy can be observed, compared to those who did not receive antibiotic therapy, thus in the case of subjects who received antibiotic therapy, the absence or the presence of a small amount of intraperitoneal fluid, which has a serocitrine appearance, as well as the absence of macroscopic changes at the level of unaffected intraperitoneal organs, can be observed. Microscopically, it can be seen that in the subjects treated with Meropenem, changes in the parietal peritoneum were minimal. CONCLUSIONS: Antibiotic therapy with Meropenem in acute peritonitis has a survival rate comparable to peritoneal lavage and source control.

Characterization and In Vitro and In Vivo Assessment of a Novel Cellulose Acetate-Coated Mg-Based Alloy for Orthopedic Applications.

Despite their good biocompatibility and adequate mechanical behavior, the main limitation of Mg alloys might be their high degradation rates in a physiological environment. In this study, a novel Mg-based alloy exhibiting an elastic modulus E = 42 GPa, Mg-1Ca-0.2Mn-0.6Zr, was synthesized and thermo-mechanically processed. In order to improve its performance as a temporary bone implant, a coating based on cellulose acetate (CA) was realized by using the dipping method. The formation of the polymer coating was demonstrated by FT-IR, XPS, SEM and corrosion behavior comparative analyses of both uncoated and CA-coated alloys. The potentiodynamic polarization test revealed that the CA coating significantly improved the corrosion resistance of the Mg alloy. Using a series of in vitro and in vivo experiments, the biocompatibility of both groups of biomaterials was assessed. In vitro experiments demonstrated that the media containing their extracts showed good cytocompatibility on MC3T3-E1 pre-osteoblasts in terms of cell adhesion and spreading, viability, proliferation and osteogenic differentiation. In vivo studies conducted in rats revealed that the intramedullary coated implant for fixation of femur fracture was more efficient in inducing bone regeneration than the uncoated one. In this manner, the present study suggests that the CA-coated Mg-based alloy holds promise for orthopedic aplications.