Search Results (72)

Background: The process of healing skin wounds frequently faces obstacles due to inadequate repair. Even though recombinant Epidermal Growth Factor (EGF) is a significant therapeutic agent, its short half-life and instability limit its clinical application. The study’s objective was to establish a lipid nanoparticle (LNP) delivery method for efficiently transporting EGF mRNA, with the goal of achieving sustained local protein expression to aid in wound healing. Methods: EGF mRNA was produced through in vitro transcription and enclosed in pH-sensitive LNPs using microfluidic techniques. The LNP-mRNAEGF’s physicochemical attributes, stability, and biocompatibility were assessed. Its effects on the proliferation and migration of HaCaT cells and on EGF expression were assessed in vitro. The therapeutic effectiveness was assessed using a mouse model with full-thickness skin defects and compared to control groups (saline, empty LNP, recombinant EGF). The study analyzed wound closure rate, histology, immunofluorescence, and systemic safety. Results: The LNP-mRNA_EGF formulation showed a spherical shape and demonstrated good stability. In vitro, it showed excellent biocompatibility, facilitated prolonged EGF expression in HaCaT cells depending on the dose for more than 72 h, and greatly enhanced cell proliferation and migration. In vivo, a single dose of LNP-mRNA_EGF greatly sped up wound healing, almost completely closing the wound by day 10, and was much more effective than all control groups. Histological and immunofluorescence analyses revealed enhanced re-epithelialization, significantly increased and optimized collagen I/III deposition, and an upregulated expression of EGF and E-cadherin. Moreover, no significant toxicity was found in the systemic safety assessment. Conclusions: The LNP-based EGF mRNA delivery platform enables efficient and sustained local protein expression via a single administration. It offers a promising translational strategy for protein replacement therapy in skin repair by significantly accelerating wound healing through enhanced re-epithelialization and optimized collagen remodeling. Full article

Background: Dry eye disease (DED) is characterized by tear film instability and a hyperosmolar ocular surface, which significantly impacts ocular health. Artificial tear solutions (ATSs) have been effective frontline treatments for DED, yet current commercially available products often provide only temporary relief, necessitating frequent daily administration. Significant efforts have been made to develop next-generation ATSs that can provide prolonged protective effects for DED. High-molecular-weight sodium hyaluronate (HA) is more commonly used in multi-dose preservative ATSs due to its longer chain lengths and rheological properties that can provide an enhanced retention time and clinical comfort and effects. The current methods to evaluate ATSs have largely focused on human biocompatibility and rheological testing and often overlook the dynamic nature of cellular phenotypes or the protective mechanisms at a cellular level. Therefore, this study developed novel in vitro mammalian cell assays involving human corneal epithelial cells (HCECs) to comprehensively assess ATSs with HA for biocompatibility and efficacy. Methods: We evaluated cellular viability across varying severities in two distinct DED models: desiccation and hyperosmotic stress. Simultaneously, time-lapse imaging coupled with computational image analyses quantified subtle, yet significant, cellular morphological changes under these stress condition. Results: Our assays revealed that ATSs provide significant, yet varying, protection against mild, medium, and harsh desiccation stress, as well as hyperosmotic conditions. This study also made a key insight that was the observation that DED conditions induce drastic HCEC morphological changes, including significant cellular monolayer breakage, which were effectively mitigated by the ATS products used in this work. Conclusions: The assays presented here provide a robust standard for ATS testing, ultimately guiding the selection of more effective next-generation therapies and aiding in a greater understanding of DED pathogenesis. Full article

Background/Objectives: Caffeine is a well-established ergogenic aid for endurance performance. However, the optimal intake strategy, specifically the administration method and dosage, remains uncertain. This systematic review and network meta-analysis compared the effectiveness of different caffeine administration methods and dosages on time-trial performance. Methods: A systematic review and network meta-analysis were conducted following PRISMA guidelines. A systematic search of PubMed, Embase, Web of Science, Scopus, and SPORTDiscus was conducted up to July 2025. Eligible studies were independently screened and quality-assessed by two reviewers. Pairwise and network meta-analyses were conducted to examine the effects of caffeine administration methods (e.g., capsules/tablets, gum, mouth rinse) and dosages (low: ≤3 mg/kg; moderate: 4–6 mg/kg) on time-trial performance. Results: Forty-eight studies with 612 participants were included. Low-dose capsules most effectively reduced completion time (standardized mean differences [SMD] = −0.34; 95% confidence interval [CI] −0.62, −0.06), followed by moderate-dose capsules (SMD = −0.31; 95% CI: −0.45, −0.17) and moderate-dose gum (SMD = −0.30; 95% CI: −0.57, −0.02). Low-dose capsules also had the highest probability of improving mean power output (SMD = 0.38; 95% CI: 0.09, 0.67), with moderate-dose capsules ranking second (SMD = 0.30; 95% CI: 0.12, 0.48). Conclusions: This systematic review and network meta-analysis identified low-dose caffeine capsules (≈3 mg/kg) as the most effective strategy for improving time-trial performance, with moderate-dose capsules and gum serving as viable alternatives. While these findings provide robust, actionable evidence for practitioners, meaningful inter-individual variability persists. Accordingly, future studies should integrate deeper mechanistic profiling (e.g., genetics and body composition) to advance personalized, evidence-based caffeine supplementation for athletes. Full article

Background: Linezolid standard dosing is typically applied in ICU without adjustments, even in renal impairment. This study examines serum concentration variability by renal function or CRRT administration in patients receiving 1200 mg/day of linezolid. Methods: This retrospective, single-center, non-randomized observational study was conducted at Niguarda Hospital (Milan, Italy) on data from the two-year period 2023–2024. ICU patients receiving linezolid, with a renal function determination and trough TDM performed at steady-state were included and stratified by renal function or CRRT status. Results: 54 patients were included, with 18 (33%) undergoing CRRT (CVVH). CRRT patients presented higher median linezolid concentrations (4.6 mg/L) than non-CRRT patients (3.2 mg/L), and a lower risk of underdosing (17% vs. 39%). CRRT patients showed significantly lower concentrations (4.6 mg/L vs. 10 mg/L, p = 0.007) than non-CRRT patients with renal function ≤ 30 mL/min, with fewer out-of-range levels (39% vs. 91%, p = 0.008) and overdosing (22% vs. 73%, p = 0.018). A significant inverse correlation was found between renal function and linezolid levels (Spearman’s rho = −0.61, p < 0.001), with CRRT patients exhibiting concentrations comparable to those of individuals with moderately impaired renal function. Continuous infusion resulted in significantly higher median concentrations (7.2 mg/L) than extended infusion (2.7 mg/L), with an increased risk of overdosing (47% vs. 17%; p = 0.018). Conclusions: After standard-dosing administration, linezolid levels vary widely in critically ill patients. Renal function significantly affects pharmacokinetics: severe impairment increases overdose risk, while ARC may cause underdosing. Standard-dosing appears adequate in CRRT patients, with levels similar to moderate-impairment. Continuous infusion aids target attainment in normal or ARC patients but raises overdose risk in severe impairment. TDM-based personalized dosing seems crucial to optimize therapy and reduce toxicity or failure. Full article

In this report, we showed that oral administration of Dendrobium Taiseed Tosnobile (DTT, also known as Taiwan Emperor No.1) allowed Lewis Lung Carcinoma (LLC) tumor-bearing mice to maintain body weight and grip strength in a dose-dependent manner. Histological analysis showed that treatment with DTT water extract significantly reduced muscle fiber damage by inducing muscle regeneration and improved the cross-sectional area of the rectus femoris, soleus, and gastrocnemius of LLC tumor-bearing C57BL/6 female mice. Further studies revealed that DTT water extract also reduced the expression of inflammatory cytokines such as IL-6 and TNF-α, both in vitro and in vivo. Other analyses showed that DTT water extract promoted the differentiation of C2C12 myoblasts with or without IL-6 by maintaining Myosin Heavy Chain (MyHC) levels. This suggests that DTT water extract acts against muscle wasting via multiple mechanisms. Interestingly, vitamin B1 was identified as an ingredient in DTT water extract through an HPLC analysis. Vitamin B1 was shown to ameliorate IL-6 but not TNF-α generation in active THP-1 cells and protected C2C12 myotubes against IL-6. Further studies showed that DTT and vitamin B1 promoted the multi-nucleus fusion step of C2C12 differentiation by inducing E-cadherin-β-catenin expression with or without IL-6 treatment. In summary, DTT water extract protects muscle cells under cancer conditions through direct and indirect mechanisms, with vitamin B1 being a key functional ingredient that reduces IL-6 generation and aids muscle cell fusion against IL-6 treatment. Full article

Lymphomas remain a significant cause of morbidity and mortality among patients living with HIV. Although the introduction of antiretroviral therapy has led to a reduction in the incidence of AIDS-related lymphomas (ARL) and an overall improvement in prognosis, these malignancies continue to pose a considerable clinical challenge. Beyond the inherent complexity of lymphoma treatment itself, the management of comorbidities, particularly infections, represents a therapeutic obstacle. Here, we review the published evidence on ARL complicated by COVID-19. Despite the fact that nearly 800 million confirmed cases of SARS-CoV-2 infection have been reported so far, only five cases of ARL and COVID-19 have been published, among whom most patients experienced a mild course of SARS-CoV-2 infection, with only one case progressing to severe COVID-19 that required oxygen therapy and prolonged hospitalization. Additionally, we present another case of a 49-year-old male patient with newly diagnosed ARL, Epstein–Barr virus (EBV)-positive, diffuse large B-cell lymphoma, not otherwise specified, complicated by prolonged SARS-CoV-2 infection. Although initially asymptomatic, the patient subsequently experienced transient respiratory failure. Despite administration of molnupiravir, both SARS-CoV-2 antigen and RT-qPCR tests remained positive for a minimum of 113 days. The prolonged SARS-CoV-2 infection, in conjunction with other opportunistic infections, impeded the delivery of adequate chemotherapy dose intensity and contributed to disease progression and ultimately the patient’s death. This case and review of the literature underscores the diversity of the clinical course of SARS-CoV-2 infection in patients with ARL and highlights the associated challenges in delivering optimal anti-lymphoma therapy in those patients. Full article

Background: Electronic monitoring adherence devices (EAMDs) are increasingly being utilized in various healthcare settings to track medication adherence. Objective: To determine the accuracy of the Sensal Health MyAide™ Smart Doc in capturing dose removal from the vial, specifically the time of dose removal and the number of pills removed for each actuation of the device. Methods: This validation study compares the device’s recording of dose withdrawals from a prescription vial by simulated patients against reference documentation reported using MS Forms by the participants. Three participants completed a 4-day study consisting of two non-consecutive 1 h sessions per day encompassing six actuations from the prescription vial to be captured by the Sensal Health MyAide™ Smart Dock after their informed consent was obtained. Statistical analysis included percent agreement and Cohen’s kappa assessing agreement between user-reported data and electronic measurement data recorded by the MyAide™ Smart Dock. Outcome measures included confirmation of the specific user, time of dose removal (±1 min), and the number of pills withdrawn. Results: Three subjects were recruited to provide data for a total of 144 actuations. The study found perfect 100% agreement across the number of pills withdrawn and specific users withdrawing the pills and 99% agreement for the time of administration. The Cohen’s kappa values for the outcome measures were 1.00 (95%CI [1.00, 1.00]) for the number of pills dispensed and specific user and 0.993 (95%CI [0.990, 0.996]) for the time of administration. Conclusions: This study found that the Sensal Health MyAide™ Smart Dock can accurately record the time of administration, the number of pills dispensed, and the identity of the user dispensing the pills. Full article

Probiotics containing Lactobacillus spp. have demonstrated immunological and gastrointestinal benefits and may aid in recovery from mood disorders. However, evidence of their mood-modulating efficacy remains inconsistent. Aim: To analyze the efficacy of probiotic interventions with Lactobacillus spp. in modulating mood in humans. A scoping review was conducted following the PRISMA guidelines. A systematic search of the PubMed and Scopus databases was performed using nine Boolean combinations of the terms “mental”, “mental diseases”, “mental disorders”, “gastrointestinal microbiome”, “gut microbiome”, “gut microbiota”, and “lactobacillus”. The search was limited to clinical trials published in English and limited to ten years of publication. Eligible studies met the following criteria: (a) probiotic interventions in adults, with or without mood disturbances; (b) the use of Lactobacillus spp., either alone or in combination; (c) mood assessment instruments applied pre- and post-intervention; and (d) reporting of probiotic concentrations. Trials involving populations with other psychiatric or neurological diagnoses or those combining probiotics with additional mood-modulating nutrients were excluded. From 3291 records, 17 clinical trials met the inclusion criteria. Data extracted included the author, year, population, country of origin, probiotic strain(s), dosage, intervention mode and duration, and outcomes related to the microbial composition, biomarkers, and microbial metabolites. Trials were categorized by probiotic type (single vs. multi-species) and participant profile (healthy individuals and those with depressive symptoms or specific physiological conditions). Preliminary evidence from single-strain interventions, particularly high-dose L. plantarum administered for ≥8 weeks, suggests potential improvements in anxiety, sleep quality, and inflammatory biomarkers. Multi-species formulations yielded reductions in depressive symptoms and changes in neurobiological markers. Nonetheless, substantial heterogeneity in strains, dosages, durations, and outcome measures limited cross-study comparisons. Lactobacillus spp. interventions show promising mood-modulating potential, especially with specific strains and prolonged administration. Standardized protocols, rigorous controls, and clearly defined clinical cohorts are needed to establish robust, evidence-based recommendations. Full article

Introduction: Near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG) is now widely regarded as a valuable aid in decision-making for complex hepatobiliary procedures, with increasing support from recent studies. Methods: We performed a systematic review following PRISMA guidelines, utilizing PubMed, CINAHL, and EMBASE databases to locate studies on the perioperative use ICG in pediatric hepatobiliary surgeries. Two independent reviewers assessed all articles for eligibility based on predefined inclusion criteria. We collected data on study design, patient demographics, surgical indications, ICG dosing, timing of ICG injection, and perioperative outcomes. Results: Forty-three articles, including 930 pediatric patients, from 1989 to 2025 met the inclusion criteria for narrative synthesis in our systematic review, of which 22/43 (51.2%) were retrospective studies, 15/43 were case reports (34.9%), 3/43 (7.0%) were experimental studies, and the other three were prospective comparative studies (7.0%). The current clinical applications of ICG in hepatobiliary pediatric surgery include bile duct surgery (cholecystectomy, choledochal cyst, biliary atresia), reported in 17 articles (39.5%), liver tumor resection, reported in 15 articles (34.9%), liver transplantation, reported in 6 articles (14.6%), and liver function determination, reported in 5 articles (12.2%). Conclusions: ICG fluorescence navigation in pediatric hepatobiliary surgery is a highly promising and safe technology that allows for the intraoperative localization of anatomic biliary structures, aids in the identification and resection of liver tumors, and can accurately determine hepatic function. The lack of comparative and prospective studies, and the variability of the dose and timing of administration are the main limitations. Full article

Background/Objectives: The oral cavity represents a convenient route of administration for drugs that exhibit significant hepatic first-pass extraction. In this study, the mucosal permeation properties of selected active pharmaceutical ingredients (APIs) incorporated into oral cavity drug products that are approved by the U.S. Food and Drug Administration were quantified using the human-derived sublingual HO-1-u-1 and buccal EpiOral™ in vitro tissue models. Methods: Epithelial barrier properties were monitored using propranolol and Lucifer Yellow as prototypic transcellular and paracellular markers. APIs were dissolved in artificial saliva, pH 6.7, and transepithelial flux from the apical to the basolateral compartment was quantified using HPLC. Results: Apparent permeability coefficients (Papp) calculated for these APIs in the sublingual HO-1-u-1 tissue model varied from Papp = 2.72 ± 0.06 × 10⁻⁵ cm/s for asenapine to Papp = 6.21 ± 2.60 × 10⁻⁵ cm/s for naloxone. In contrast, the buccal EpiOral™ tissue model demonstrated greater discrimination power in terms of permeation properties for the same APIs, with values ranging from Papp = 3.31 ± 0.83 × 10⁻⁷ cm/s for acyclovir to Papp = 2.56 ± 0.68 × 10⁻⁵ cm/s for sufentanil. The tissue-associated dose fraction recovered at the end of the transport experiment was significantly increased in the buccal EpiOral™ tissue model, reaching up to 8.5% for sufentanil. Conclusions: Experimental permeation data collected for selected APIs in FDA-approved oral cavity products will serve as a training set to aid the development of predictive computational models for improving algorithms that describe drug absorption from the oral cavity. Following a robust in vitro–in vivo correlation analysis, it is expected that such innovative in silico modeling strategies will the accelerate development of generic oral cavity products by facilitating the utility of model-integrated evidence to support decision making in generic drug development and regulatory approval. Full article

Caffeine is a weak, nonselective adenosine receptor antagonist. At low-to-moderate doses, caffeine has a stimulating effect; however, at higher doses, it can act as a depressant. It can function both as a neuroprotectant and a neurotoxin. In experimental Traumatic Brain Injury (TBI), administration of this psychoactive drug has been associated with beneficial or detrimental effects, depending on the dose, model, and timing. In a healthy brain, caffeine can enhance alertness and promote wakefulness. However, its consumption during late adolescence and early adulthood disrupts normal pruning processes in the context of repetitive moderate TBI (mTBI), leading to changes in dendritic spine morphology, resulting in neurological and behavioral impairments. Caffeine can potentially reduce TBI-associated intracranial pressure, oxidative stress, lipid peroxidation, cytotoxic edema, inflammation, and apoptosis. It can enhance alertness and reduce mental fatigue, which is critical for the cognitive rehabilitation of TBI patients. Additionally, caffeine positively affects immune cells and aids recovery post-TBI. Antagonizing adenosine receptors involved in controlling synaptic transmission, synaptic plasticity, and synapse toxicity can improve cognitive function. Conversely, studies have also shown that caffeine consumers report significantly higher somatic discomfort compared to non-consumers. This review aims to explore various studies and thoroughly examine the positive and negative roles of caffeine in TBI. Full article

Background/Aim: This case report navigates through the challenges of a complex clinical scenario involving germ cell tumors (GCTs), one of the most frequently encountered malignancies in adolescents and young adults. Case report: We present the case of an 18-year-old patient exhibiting atypical clinical manifestations, prompting emergent extensive surgical intervention. Upon admission to the Oncology Department, the adolescent presented with jaundice and dyspnea, being diagnosed with pure non-seminomatous embryonal carcinoma, a poor-risk prognosis group. Based on his prognostic group, the patient should have undergone chemotherapy with a well standardized regimen, but the imminent “liver visceral crisis” did not allow for the standard dose chemotherapy administration, so an adapted regimen of chemotherapy was considered and the full number of cycles was applied after this induction cycle. The treatment journey was protracted, emphasizing the need for early recognition and intervention in such cases. A comprehensive ongoing evaluation, including imagistic examinations and laboratory tests, revealed the presence of extensive refractory disease, which led to urgent treatment. Conclusions: This case provides valuable insights into the management of advanced testicular germ cell tumor in young patients facing imminent organ failure and underlines the importance of interdisciplinary collaboration. Understanding the complexities of this condition can aid in improving patient outcomes and enhancing the quality of care provided. Full article

Background: Indocyanine green (ICG) fluorescence has seen extensive application across medical and surgical fields, praised for its real-time navigation capabilities and low toxicity. Initially employed to assess liver function, ICG fluorescence is now integral to liver surgery, aiding in tumor detection, liver segmentation, and the visualization of bile leaks. This study reviews current protocols and ICG fluorescence applications in liver surgery, with a focus on optimizing timing and dosage based on clinical indications. Methods: Following PRISMA guidelines, we systematically reviewed the literature up to 27 January 2024, using PubMed and Medline to identify studies on ICG fluorescence used in liver surgery. A systematic review was performed to evaluate dosage and timing protocols for ICG administration. Results: Of 1093 initial articles, 140 studies, covering a total of 3739 patients, were included. The studies primarily addressed tumor detection (40%), liver segmentation (34.6%), and both (21.4%). The most common ICG fluorescence dose for tumor detection was 0.5 mg/kg, with administration occurring from days to weeks pre-surgery. Various near-infrared (NIR) camera systems were utilized, with the PINPOINT system most frequently cited. Tumor detection rates averaged 87.4%, with a 10.5% false-positive rate. Additional applications include the detection of bile leaks, lymph nodes, and vascular and biliary structures. Conclusions: ICG fluorescence imaging has emerged as a valuable tool in liver surgery, enhancing real-time navigation and improving clinical outcomes. Standardizing protocols could further enhance ICG fluorescence efficacy and reliability, benefitting patient care in hepatic surgeries. Full article

Drug-induced liver injury (DILI) is one of the main causes of acute liver failure in children. Its incidence is probably underestimated, as specific diagnostic tools are currently lacking. Over 1000 known drugs cause DILI, and the list is expanding. The aim of this review is to describe DILI pathogenesis and emphasize the drugs accountable for child DILI in order to aid its recognition. Intrinsic DILI is well described in terms of mechanism, incriminated drugs, and toxic dose. Conversely, idiosyncratic DILI (iDILI) is unpredictable, occurring as a result of a particular response to drug administration, and its occurrence cannot be foreseen in clinical studies. Half of pediatric iDILI cases are linked to antibiotics, mostly amoxicillin–clavulanate, in the immune-allergic group, while autoimmune DILI is the hallmark of minocycline and nitrofurantoin. Secondly, antiepileptics are responsible for 20% of pediatric iDILI cases, children being more prone to iDILI caused by these agents than adults. A similar tendency was observed in anti-tuberculosis drugs, higher incidences being reported in children below three years old. Current data show growing cases of iDILI related to antineoplastic agents, atomoxetine, and albendazole, so that it is advisable for clinicians to maintain a high index of suspicion regarding iDILI. Full article

Chronic non-cancer pain, defined by the Center for Disease Control and Prevention (CDC) as lasting beyond three months, significantly affects individuals’ quality of life and is often linked to various medical conditions or injuries. Its management is complex. Cannabis, containing the key compounds Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), has garnered interest for its potential in pain management, though it remains controversial due to its psychoactive effects and illegal status in many countries. THC provides pain relief by blocking nociceptive stimuli but has psychoactive effects and may potentially induce dependency. CBD has calming and antipsychotic properties. The inhalation of cannabis offers quick relief but poses respiratory risks, while its oral administrations are safer but act more slowly. Short-term cannabis use can impair cognition and motor skills, while long-term use may lead to dependency and cognitive decline, especially if used from an early age. Adverse effects vary by gender and prior use, with addiction mainly linked to THC and influenced by genetics. Despite these risks, patients often report more benefits, such as improved quality of life and reduced opioid use, although the evidence remains inconclusive. The legal landscape for medical cannabis varies globally, with some positive public health outcomes like reduced opioid-related issues in areas where it is legalized. Cannabis shows promise in managing chronic pain, but its psychoactive effects and dependency risks necessitate cautious use. Future research should prioritize long-term clinical trials to establish optimal dosing, efficacy, and safety, aiding in the development of informed guidelines for safe cannabis use in chronic pain management. This review examines the use of cannabis in managing chronic non-cancer pain, focusing on its benefits, drawbacks, mechanisms, delivery methods, and impact on quality of life. Full article