Nicotinamide adenine dinucleotide (NAD+) and its metabolites function as critical regulators to maintain physiologic processes, enabling the plastic cells to adapt to environmental changes including nutrient perturbation, genotoxic factors, circadian disorder, infection, inflammation and xenobiotics. These effects are mainly achieved by the driving effect of NAD+ on metabolic pathways as enzyme cofactors transferring hydrogen in oxidation-reduction reactions. Besides, multiple NAD+-dependent enzymes are involved in physiology either by post-synthesis chemical modification of DNA, RNA and proteins, or releasing second messenger cyclic ADP-ribose (cADPR) and NAADP+. Prolonged disequilibrium of NAD+ metabolism disturbs the physiological functions, resulting in diseases including metabolic diseases, cancer, aging and neurodegeneration disorder. In this review, we summarize recent advances in our understanding of the molecular mechanisms of NAD+-regulated physiological responses to stresses, the contribution of NAD+ deficiency to various diseases via manipulating cellular communication networks and the potential new avenues for therapeutic intervention.
Burn is an under-appreciated trauma that is associated with unacceptably high morbidity and mortality. Although the survival rate after devastating burn injuries has continued to increase in previous decades due to medical advances in burn wound care, nutritional and fluid resuscitation and improved infection control practices, there are still large numbers of patients at a high risk of death. One of the most common complications of burn is sepsis, which is defined as “severe organ dysfunction attributed to host's disordered response to infection” and is the primary cause of death in burn patients. Indeed, burn injuries are accompanied by a series of events that lead to sepsis and multiple organ dysfunction syndrome, such as a hypovolaemic state, immune and inflammatory responses and metabolic changes. Therefore, clear diagnostic criteria and predictive biomarkers are especially important in the prevention and treatment of sepsis and septic shock. In this review, we focus on the pathogenesis of burn wound infection and the post-burn events leading to sepsis. Moreover, the clinical and promising biomarkers of burn sepsis will also be summarized.
Abstract....With the development of nanomedical technology, the application of various novel nanomaterials in the biomedical field has been greatly developed in recent years. MXenes, which are new inorganic nanomaterials with ultrathin atomic thickness, consist of layered transition metal carbides and nitrides or carbonitrides and have the general structural formula Mn+1XnTx (n = 1–3). Based on the unique structural features of MXenes, such as ultrathin atomic thickness and high specific surface area, and their excellent physicochemical properties, such as high photothermal conversion efficiency and antibacterial properties, MXenes have been widely applied in the biomedical field. This review systematically summarizes the application of MXene-based materials in biomedicine. The first section is a brief summary of their synthesis methods and surface modification strategies, which is followed by a focused overview and analysis of MXenes applications in biosensors, diagnosis, therapy, antibacterial agents, and implants, among other areas. We also review two popular research areas: wearable devices and immunotherapy. Finally, the difficulties and research progress in the clinical translation of MXene-based materials in biomedical applications are briefly discussed.
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Clinically, postoperative adhesions are common and serious complications, which almost always happen after abdominal or pelvic surgery. The adhesion development process is accompanied by increased inflammatory cell infiltration and oxygen-free radical production. In this study, the naturally occurring antioxidative and anti-inflammatory compounds extracted from Turkish galls by ethyl acetate (GEA) were encapsulated into an injectable and biodegradable thermosensitive hydrogel. Antiadhesion efficacy of the barrier system (GEA-NP/H) was tested on a rat peritoneum injury-cecum abrasion model. Upon injection, the mildly viscous liquid formed a potent physical barrier over the injured cecum and peritoneum without any additional cross-linkers or light sources. Once formed, GEA-NP/H acted as a durable wound dressing for more than 5 days, as well as a sustained drug depot of GEA. The polymer hydrogel can be degraded and absorbed gradually. After 14 days, severe adhesion occurred among rats treated with normal saline and GEA-loaded nanoparticles (GEA-NP). Whereas, frequency of score 1 adhesion among the blank hydrogel group is 30%, and 90% of the rats from GEA-NP/H group exhibited no adhesion. In addition, pathological sections and scanning electron microscopy assay demonstrated that operative defects treated with GEA-NP/H suffered from mild oxidative stress and inflammatory damages at early days after injury, as well as accelerated wound healing and more mature mesothelial cell deposition at the 14th day in contrast to the blank hydrogel treatment. Therefore, the study provided an available biodegradable hydrogel barrier to effectively prevent postsurgical adhesion.
The neutrophil-to-lymphocyte ratio (NLR) reflects the systematic inflammatory status, and the aspartate aminotransferase-to-alanine aminotransferase ratio (AAR) is a biomarker of liver fibrosis and cirrhosis. These values can be conveniently obtained from routine blood tests; however, their combined clinical utility has not been extensively studied in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). This study aimed to investigate the prognostic value of NLR-AAR in patients with unresectable HCC undergoing TACE. Data for 760 patients with newly diagnosed HCC were retrospectively evaluated. The NLR-AAR was calculated as follows: patients in whom both the NLR and AAR were elevated according to the receiver operating characteristic (ROC) curve analysis were assigned a score of 2; patients showing an elevation in one or neither of these indicators were assigned a score of 1 or 0, respectively. Univariate and multivariate analyses were performed to identify the clinicopathological variables associated with overall survival. An ROC curve was also generated and the area under the curve (AUC) was calculated to evaluate the discriminatory ability of each index at 1, 3, and 5 years of follow-up, as well as overall. The NLR-AAR consistently had a greater AUC value at 1 year (0.669), 3 years (0.667), and 5 years (0.671) post-TACE compared with either NLR or AAR alone. The median survival times of patients with a NLR-AAR of 0, 1, and 2 were 31.0 (95% confidence interval [CI] 24.0–38.0), 15.0 (95% CI 11.2–18.8), and 5.0 (95% CI 4.0–5.9) months, respectively (P < .001). Multivariate analysis showed that the NLR-AAR, elevated total bilirubin level, and vascular invasion were independently associated with overall survival. NLR and AAR, when combined to produce an inflammation-based index and fibrosis score, is an independent marker of poor prognosis in patients with HCC receiving TACE.
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