EXCLI Journal最新文献

Bilateral force control and coordination in upper and lower limbs are important functions for executing activities of daily living. Although upper and lower limbs may reveal distinct bilateral motor control patterns because of different motor networks involvements, no one has examined the possibility that upper and lower limbs reveal distinct bilateral force control and coordination patterns. This study investigated bilateral force control and coordination patterns between upper and lower limbs in healthy young adults. Thirty-two healthy young adults (mean±SD of age = 23.2±2.2 years; 16 Females) performed bilateral hand-grip and ankle-dorsiflexion force control tasks at 10 % and 40 % of maximal voluntary contraction. Bilateral force control performances were evaluated by calculating mean force, force symmetry, force accuracy, and force variability. To estimate bilateral force coordination, we used cross-correlation with time lag. Further, we examined the relationship between bilateral force control and coordination patterns of upper and lower limbs by conducting Pearson's correlation analysis. Bilateral maximal and mean forces of lower limbs were significantly less than those for upper limbs. At higher targeted force level, force accuracy and variability in lower limbs were significantly lower than those for upper limbs. More negative correlation coefficient values appeared in lower limbs as compared with upper limbs. Finally, bilateral force control performances in upper limbs were related to those in lower limbs although no significant correlation was observed for interlimb coordination patterns. These findings suggest that bilateral motor control and coordination patterns were different between upper and lower limbs although the level of bilateral upper and lower motor control capabilities was presumably influenced by shared motor control processes for each individual. See also the graphical abstract(Fig. 1).

This review analyzes case reports of adverse drug reactions (ADRs) attributed to etoricoxib, with particular emphasis on Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), fixed drug eruptions (FDE), atrial fibrillation, hypertension, thrombocytopenia (TP), immune hemolytic anemia (IHA), acute generalized exanthematous pustulosis (AGEP), maculopapular rash, pretibial erythema with edema, and reversible cerebral vasoconstriction syndrome (RCVS). Although infrequent, these severe hypersensitivity and cardiovascular events pose significant clinical risks due to their association with substantial morbidity and, in some cases, mortality. The primary aim of this review is to consolidate available clinical evidence to evaluate the causality, characteristic clinical presentations, and broader safety implications of etoricoxib in relation to these adverse outcomes. While SJS/TEN are marked by widespread epidermal necrosis and detachment, FDE typically recurs at fixed sites with residual pigmentation. Hematological complications such as drug-induced (TP) and Drug-induced IHA have also been reported, presenting as sudden platelet decline or severe hemolysis, respectively. These adverse effects often appear within hours to weeks of initiating therapy. Cutaneous manifestations, including exanthematous pustulosis and maculopapular rashes, further complicate the drug's safety profile. Etoricoxib's pro-thrombotic potential, possibly linked to COX-2 selectivity, remains a cardiovascular concern. Causality assessments via the Naranjo Scale and WHO-UMC often support a probable link. These findings underscore the necessity for careful evaluation of patient history, immediate drug discontinuation upon clinical suspicion, and strengthened pharmacovigilance systems to better capture and characterize the full range of these rare yet serious reactions. See also the graphical abstract(Fig. 1).

Polyphenols are naturally occurring compounds that can be found in plant-based foods, including fruits, vegetables, nuts, seeds, herbs, spices, and beverages, the use of which has been linked to enhanced brain health and cognitive function. These natural molecules are broadly classified into two main groups: flavonoids and non-flavonoid polyphenols, the latter including phenolic acids, stilbenes, and tannins. Flavonoids are primarily known for their potent antioxidant properties, which help neutralize harmful reactive oxygen species (ROS) in the brain, thereby reducing oxidative stress, a key contributor to neurodegenerative diseases. In addition to their antioxidant effects, flavonoids have been shown to modulate inflammation, enhance neuronal survival, and support neurogenesis, all of which are critical for maintaining cognitive function. Phenolic acids possess strong antioxidant properties and are believed to protect brain cells from oxidative damage. Neuroprotective effects of these molecules can also depend on their ability to modulate signaling pathways associated with inflammation and neuronal apoptosis. Among polyphenols, hydroxycinnamic acids such as caffeic acid have been shown to enhance blood-brain barrier permeability, which may increase the delivery of other protective compounds to the brain. Another compound of interest is represented by resveratrol, a stilbene extensively studied for its potential neuroprotective properties related to its ability to activate the sirtuin pathway, a molecular signaling pathway involved in cellular stress response and aging. Lignans, on the other hand, have shown promise in reducing neuroinflammation and oxidative stress, which could help slow the progression of neurodegenerative diseases and cognitive decline. Polyphenols belonging to different subclasses, such as flavonoids, phenolic acids, stilbenes, and lignans, exert neuroprotective effects by regulating microglial activation, suppressing pro-inflammatory cytokines, and mitigating oxidative stress. These compounds act through multiple signaling pathways, including NF-κB, MAPK, and Nrf2, and they may also influence genetic regulation of inflammation and immune responses at brain level. Despite their potential for brain health and cognitive function, polyphenols are often characterized by low bioavailability, something that deserves attention when considering their therapeutic potential. Future translational studies are needed to better understand the right dosage, the overall diet, the correct target population, as well as ideal formulations allowing to overcome bioavailability limitations. See also the graphical abstract(Fig. 1).

Berberine (BBR) is a plant-derived alkaloid that has been traditionally used in Chinese medicine to treat diarrhea. In recent years, accumulating evidence has highlighted its broad therapeutic potential across multiple organ systems. This review systematically examines the pharmacological mechanisms and therapeutic applications of BBR in cancer, as well as in digestive, metabolic, cardiovascular, and neurological diseases. The effects of BBR on endogenous factors-such as energy metabolism, immune responses, cellular homeostasis, and gene expression-are discussed, along with its regulation of cellular functions and inflammatory responses. In addition, we explore BBR's actions on exogenous factors, particularly the gut microbiota. The review also summarizes emerging molecular targets of BBR and addresses current clinical applications, as well as novel strategies to improve its low oral bioavailability. By integrating findings from basic, translational, and clinical research, this review provides a comprehensive overview of BBR's therapeutic potential and supports its integration into modern medical practice. See also the graphical abstract(Fig. 1).

Metabolic syndrome (MetS), is a non-communicable disorder caused by impaired management and storage of energy, primarily associated with unhealthy diets, sedentary lifestyles and stress. It is diagnosed when any three of the following conditions are observed, obesity (primary factor), hyperglycemia, low HDL, hypertriglyceridemia, and hypertension (ATP III guidelines). MetS affects approximately 14-34 % of the global population, highlighting significant public health concern. If left untreated, it leads to the development of other serious metabolic diseases like atherosclerosis, diabetes, PCOS, NAFLD, NASH, thyroid, cancer, sleep disturbance, osteoarthritis, anxiety, and depression. Despite ongoing research, no first-line drug currently exists for the comprehensive management of MetS. Its multifactorial nature often requires lifelong polytherapy with lifestyle intervention, raising concern over chronic drug use, drug-drug interactions, increasing morbidity and mortality. Therefore, there is a need highlighting the requirement of a single and targeted pharmacotherapy which offers a safer and more specific therapeutic approach. This review aims to identify and analyse ten key molecular targets in managing the pathogenesis of Metabolic Syndrome (MetS). These targets can further pave the way for a targeted and safer approach in the treatment of MetS. See also the graphical abstract(Fig. 1).

Sepsis remains a global health problem that causes millions of deaths each year. A rapid and accurate diagnosis is highly desired to allow a rapid use of appropriate antibiotics. A better understanding of the associated pathophysiology has been achieved these recent years. The initial appropriate immune response to infection evolves towards an overwhelmed inflammatory response involving both pro- and anti-inflammatory players that act concomitantly. It also includes cell deaths and cellular dysfunctions of leukocytes, endothelial cells and epithelial cells, associated with mitochondrial dysfunction. These dysregulations are responsible for organ impairment and alteration of immune status of circulating leukocytes. In contrast, within the tissues, an over-activation exists as illustrated by transcriptomic analyses of organs of patients deceased of sepsis, and revealed by the presence of a macrophage activation syndrome within the bone marrow. Despite progresses in understanding the mechanisms underlying sepsis and despite successful therapies in animal models, no real new therapies have emerged these recent decades. This failure may reflect the yin yang aspect of the same players of the host response such as fever, release of cytokines, or coagulation which can display both a beneficial or a detrimental role. Great hopes are now expected from precision medicine, based on patients' endotypes which should help to decipher the patient's sub-groups who could benefit from the different treatments, or to define some appropriate time windows for a given treatment. See also the graphical abstract(Fig. 1).

This study investigated the therapeutic impact of dual immune checkpoint inhibition targeting TIGIT and VISTA in non-small cell lung cancer (NSCLC). Current monotherapies have failed to produce consistent and durable responses owing to tumor heterogeneity and immune evasion. By evaluating the biological and immunomodulatory roles of TIGIT and VISTA, this study provides a rationale for their simultaneous blockade. Preclinical models have shown that this dual strategy not only revitalizes T-cell function but also alters the suppressive tumor microenvironment, leading to improved antitumor immunity in mice. Preliminary clinical data suggest potential survival benefits; however, the long-term outcomes and resistance dynamics remain uncertain. These findings suggest a paradigm shift toward precision-designed, multi-target immunotherapies. Future studies should integrate molecular profiling, adaptive clinical trial designs, and follow-up models to optimize patient selection and sustain therapeutic benefits. See also the graphical abstract(Fig. 1).

Cancer is a multifactorial disease with cellular proliferative molecular networks and immune evasion properties. The well-known cancer intra- and inter-tumoral heterogeneity presents a notable limitation of the current histological and diagnostic techniques. Thus, biasing the risk of invasiveness and restricting its broader application in oncology in prognostic, survival, and treatment response differences between patients. Monolayer cell cultures have been a consistent in vitro model in cancer research throughout time. However, this system fails to replicate the complex pathogenesis of this disease, as key mechanisms underlying initiation, metastasis, drug resistance, and recurrence remain poorly understood. 3D culture models are presented as the most suitable model to better reflect the patient's tumor development. Some methods to introduce the third dimension into cell cultures is by promoting cell-cell interactions to give 3D cell structures, using scaffolds to promote growth beyond monolayers and introducing microfluidic platforms to the system. The present review provides an overview of different techniques to develop 3D culture models in oncology, the advantages compared between monolayer cell cultures, their applications, limitations, and applicability in oncology research. See also the graphical abstract(Fig. 1).