TIM-3 Expression in Endometriosis.

PROBLEM: Endometriosis is a prevalent chronic gynecological disease linked to immune dysfunction. The protein T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) plays a crucial role in immune system balance. Malfunction of TIM-3 may result in excessive immune activation and inflammatory tissue damage. Given TIM-3's established role in the development of cancer and autoimmune diseases, we decided to study its role in women suffering from endometriosis. STUDY METHOD: We included a total of 62 female patients, all of whom had undergone laparoscopic surgery. Of these, 47 had endometriosis and 15 did not. During surgery, we collected peritoneal fluid (PF) and peripheral blood (PB) samples from every patient for analysis using flow cytometry. To mark the samples, we used a panel of monoclonal antibodies and examined TIM-3 expression in their immune cells. RESULTS: Endometriosis patients in PB demonstrated a significantly lower percentage of CD56+ T cells with TIM-3 expression. As endometriosis progressed through its stages, this expression lessened. This decrease was particularly notable in women with stage III/IV endometriosis. Additionally, both women diagnosed with intestinal endometriosis and those with recent endometriosis diagnoses showed a significantly reduced percentage of CD56+ T cells expressing TIM-3. CONCLUSIONS: Patients with endometriosis exhibit diminished TIM-3 expression within circulating T cells. This warrants further investigation to discern whether it contributes to the progression of endometriosis, potentially through the amplification of autoreactive T cells and inflammation.

Natural Killer Cell Receptors and Endometriosis: A Systematic Review.

Endometriosis is a chronic inflammatory disorder, characterized by the presence of endometrial cells outside the uterine cavity. An increasing number of studies correlate the immune system with endometriosis, particularly NK receptors (NKR), which have been suggested to play an essential role in the pathogenesis of the disease. This systematic review aims to enlighten the role of NKR in endometriosis. A literature search was performed independently by two reviewers, to identify studies assessing the role of NKR in endometriosis. In total, 18 studies were included. Endometriosis pathogenesis seems to be marked by the overexpression of NK inhibitor receptors (KIRS), namely, CD158a+, KIR2DL1, CD94/NKG2A, PD-1, NKB1, and EB6, and inhibiting ligands such as PD-L1, HLA-E, HLA-G, and HLA-I. Concurrently, there is a decrease in NK-activating receptors and natural cytotoxicity receptors (NCRs), such as NKp46, NKp30, and NKG2D. The immune shift from NK surveillance to NK suppression is also apparent in the greater relative number of ITIM domains compared with ITAM domains in NKRs. In conclusion, NK receptor activity seems to dictate the immunocompetency of women to clear endometriotic cells from the peritoneal cavity. Future research could explore NKRs as therapeutic targets, such as that which is now well established in cancer therapy through immunotherapy.

Intramedullary nailing biomechanics: Evolution and challenges.

This article aims to review the biomechanical evolution of intramedullary nailing and describe the breakthrough concepts which allowed for nail improvement and its current success. The understanding of this field establishes an adequate background for forthcoming research and allows to infer on the path for future developments on intramedullary nailing. It was not until the 1940s, with the revolutionary Küntscher intramedullary nailing design, that this method was recognized as a widespread medical procedure. Such achievement was established based on the foundations created from intuition-based experiments and the first biomechanical ideologies. The nail evolved from allowing alignment and stability through press-fit fixation with nail-cortical wall friction to the nowadays nail stability achieved through interlocking screws mechanical linkage between nail and bone. Important landmarks during nail evolution comprise the introduction of flexible reaming, the progress from slotted to non-slotted nails design, the introduction of nail 'dynamization' and the use of titanium alloys as a new nail material. Current biomechanical improvement efforts aim to enhance the bone-intramedullary nail system stability. We suggested that benefit would be attained from a better understanding of the ideal mechano-biological environment at the fracture site, and future improvements will emerge from combining mechanics and biological tools.

Recent developments on intramedullary nailing: a biomechanical perspective.

Combining contributions from engineering and medicine, we highlight the biomechanical turning points in the historical evolution of the intramedullary nailing stabilization technique and discuss the recent innovations concerning increase in bone-implant system stability. Following the earliest attempts, where stabilization of long bone fractures was purely based on intuition, intramedullary nailing evolved from allowing alignment and translational control through press-fit fixation to current clinical widespread acceptance marked by the mechanical linkage between nail and bone with interlocking screws that allow alignment, translation, rotation, and length control. In an attempt to achieve an optimum interfragmentary mechanical environment, recent improvements considered the impact of different biomaterials on bone-implant stiffness. Another strategy considered the increase in the structural stability through the reduction of the number of movements between the different components that constitute the bone-implant system. Intramedullary nail improvements will most likely benefit from merging mechanics and fracture-healing biology by combining surface engineering with sensor tools associated with the innovative progress in wireless technology and with bone-healing biological active agents. Future research should aim at better understanding the ideal mechanobiological environment for each stage of fracture healing in order to allow for intramedullary nail design that satisfies such requirements.

From mechanical stimulus to bone formation: A review.

Bone is a remarkable tissue that can respond to external stimuli. The importance of mechanical forces on the mass and structural development of bone has long been accepted. This adaptation behaviour is very complex and involves multidisciplinary concepts, and significant progress has recently been made in understanding this process. In this review, we describe the state of the art studies in this area and highlight current insights while simultaneously clarifying some basic yet essential topics related to the origin of mechanical stimulus in bone, the biomechanisms associated with mechanotransduction, the nature of physiological bone stimuli and the test systems most commonly used to study the mechanical stimulation of bone.

Preparation of robust polyamide microcapsules by interfacial polycondensation of p-phenylenediamine and sebacoyl chloride and plasticization with oleic acid.

Microcapsules produced by interfacial polycondensation of p-phenylenediamine (PPD) and sebacoyl chloride (SC) were studied. The products were characterized in terms of morphology, mean diameter and effectiveness of dodecane encapsulation. The use of Tween 20 as dispersion stabilizer, in comparison with polyvinyl alcohol (PVA), reduced considerably the mean diameter of the microcapsules and originated smoother wall surfaces. When compared to ethylenediamine (EDA), microcapsules produced with PPD monomer were more rigid and brittle, prone to fracture during processing and ineffective retention of the core liquid. The use of diethylenetriamine (DETA) cross-linker in combination with PPD did not decrease capsule fragility. On the other hand, addition of a small fraction of oleic acid to the organic phase remarkably improved wall toughness and lead to successful encapsulation of the core-oil. Oleic acid is believed to act as a plasticizer. Its incorporation in the polymeric wall was demonstrated by FTIR and (1)H-NMR.

Predicting the secondary structure of proteins using machine learning algorithms.

The functions of proteins in living organisms are related to their 3-D structure, which is known to be ultimately determined by their linear sequence of amino acids that together form these macromolecules. It is, therefore, of great importance to be able to understand and predict how the protein 3D-structure arises from a particular linear sequence of amino acids. In this paper we report the application of Machine Learning methods to predict, with high values of accuracy, the secondary structure of proteins, namely alpha-helices and beta-sheets, which are intermediate levels of the local structure.