Frontiers in Pharmacology最新文献

Introduction: Researchers are increasingly exploring the use of artificial intelligence (AI) tools in evidence synthesis, a labor-intensive, time-consuming, and costly effort. This review explored and quantified the potential efficiency benefits of using automated tools as part of core evidence synthesis activities compared with human-led methods.

Methods: We searched the MEDLINE and Embase databases for English-language articles published between 2012 and 14 November 2023, and hand-searched the ISPOR presentations database (2020-2023) for articles presenting quantitative results on workload efficiency in systematic literature reviews (SLR) when AI automation tools were utilized. Data on efficiencies (time- and cost-related) were collected.

Results: We identified 25 eligible studies: 13 used machine learning, 10 used natural language processing, and once each used a systematic review automation tool and a non-specified AI tool. In 17 studies, a >50% time reduction was observed, with 5-to 6-fold decreases in abstract review time. When the number of abstracts reviewed was examined, decreases of 55%-64% were noted. Studies examining work saved over sampling at 95% recall reported 6- to 10-fold decreases in workload with automation. No studies quantified the economic impact associated with automation, although one study found that there was an overall labor reduction of >75% over manual methods during dual-screen reviews.

Discussion: AI can reduce both workload and create time efficiencies when applied to evidence gathering efforts in SLRs. These improvements can facilitate the implementation of novel approaches in decision making that consider the real-life value of health technologies. Further research should quantify the economic impact of automation in SLRs.

Background: The increased myocardial vulnerability that occurs in diabetic patients following an ischemia-reperfusion injury (I/RI) represents a significant perioperative safety risk. A comprehensive understanding of the intrinsic mechanisms underlying this phenomenon is therefore of paramount importance.

Purposes: The objective of this study is to investigate the potential mechanism of action between impaired autophagic flux and increased vulnerability in diabetic myocardium. This will provide a foundation for the clinical search for effective preventive and curative measures.

Methods: The transcriptomic alterations in autophagy-related genes following myocardial exposure to I/RI were analyzed by single-cell sequencing. This was followed by the validation of potential mechanisms of action between impaired autophagic flux and increased susceptibility at the cellular and animal levels, respectively.

Results: After I/RI in diabetic myocardium, there was a significant increase in the number of CM1 subgroups and a specific downregulation of 239 autophagy-related genes led by RILP. HE staining revealed that myocardial injury was exacerbated in diabetic mice subjected to I/RI. Transmission electron microscopy revealed that the accumulation of autophagic vesicles in cardiomyocytes of diabetic mice resulted in impaired autophagic flux. qRT-PCR revealed that the expression of RILP was significantly reduced in diabetic mice subjected to I/RI. WB showed that P62 was significantly increased and RILP was significantly decreased in diabetic mice subjected to I/RI compared to healthy mice. Inhibition of mTOR during hypoxia/reoxygenation (H/R) injury restored RILP expression and attenuated cellular injury in cardiomyocytes cultured with high glucose.

Conclusion: Following I/RI in diabetic myocardium, an increase in the CM1 subpopulation and a reduction in RILP expression result in impaired autophagic flux. Regulation of the mTOR/RILP pathway can restore impaired autophagic flux and improve myocardial vulnerability, thereby exerting cardioprotective effects.

Introduction: Corneal damage can happen due to a variety of insults, including environmental factors and iatrogenic issues. For instance, the corneal epithelium is sensitive to oxidative stress caused by reactive oxygen species (ROS) or by ultraviolet B (UVB) radiation. Moreover, the strictly correlated oxidative damage and inflammatory processes impair the corneal reparative wound healing mechanism. Corneal protection after damage remains an unmet medical need that requires urgent management. Sodium hyaluronate is known to protect the cornea against oxidative and inflammatory injury. Additionally, vitamin B12 is a good candidate for counteracting corneal damage, helping preserve visual functions.

Methods: The present study aimed to investigate the potential protective effect of an ophthalmic formulation based on 0.01% vitamin B12% and 0.15% sodium hyaluronate (DROPYAL EVO) compared to other ophthalmic formulations containing sodium hyaluronate and trehalose (TRIMIX and THEALOZ DUO). Two different in vitro models of corneal damage were carried out in corneal epithelial cells exposed to hydrogen peroxide (H₂O₂, 1 mM) or UVB (20 mJ/cm²). Cell viability, cytotoxicity, ROS production, and mRNA expression of pro-inflammatory cytokines (TNF-α and IL-1β) were assessed by MTT, LDH, 2',7'-dichlorofluorescein diacetate (DCFDA) assays and Real-time PCR, respectively. Additionally, the ability of ophthalmic formulations to affect the wound healing process in corneal epithelial cells was assessed at different time points by scratch wound healing assay.

Results: The eye drops containing vitamin B12 were able to significantly counteract oxidative and inflammatory damage in corneal epithelial cells exposed to H₂O₂ stimulus and UVB radiation, in terms of ROS production and pro-inflammatory cytokines expression. Additionally, the eye drops containing vitamin B12 obtained significantly better outcomes in terms of wound closure at 36 h and 48 h after scratching the corneal epithelial cells, compared to the other two formulations containing trehalose.

Discussion: Vitamin B12 potentially enhances the protective effect of sodium hyaluronate, accelerating the wound healing process and modulating oxidative stress and inflammation. Vitamin B12, in combination with sodium hyaluronate, could represent a promising approach to managing corneal epithelial damage. Further clinical investigations are needed to confirm this data.

Background: To develop a rational and standardized traditional Chinese medicine (TCM) good practice recommendation (GPR) methodology model that guides the formulation of recommendations grounded in clinical experience.

Methods: We adopted an exploratory sequential mixed-method to develop a methodology model by coding systematically collected literature on methodology and TCM guidelines related to TCM GPR using a best-fit framework synthesis. Then based on real-world data (published TCM guidelines), saturation tests, structural rationality validation, and discriminability tests were conducted to validate methodology model.

Results: A total of 35 methodological literature and 190 TCM guidelines were included. A TCM GPR methodology model was developed, including 3 themes, 10 sub-themes, and the relationships between themes and subthemes. The information of TCM GPR methodology model achieved data saturation. The fit indices were within the acceptable range, and were able to distinguish the overall differences between guidelines from different literature sources, development organizations, guideline types, discipline categories, and funding categories.

Conclusion: The study developed a TCM GPR methodology model which describes the definition of a TCM GPR, how to formulate it, and how to report it. The methodology modeldemonstrates good fit, discriminability, and data saturation. It can standardize the specific formulation of TCM GPRs, facilitate the scientific and rational formation of TCM GPRs, and provide theoretical and methodological guidance for the formation of TCM GPRs.

Background: Neuronal senescence is a common pathological feature of various neurodegenerative diseases, with ferroptosis playing a significant role. This study aims to investigate the role of ErbB4 receptor activation in preventing D-Galactose (D-gal)-induced neuronal senescence.

Methods: Mice subjected to D-gal-induced aging were administered a small molecule ErbB4 receptor agonist (E4A), identified via virtual screening, melatonin, or a combination of both. Behavioral assessments were conducted to evaluate therapeutic efficacy in memory and cognitive functions. Immunofluorescence staining, western blot, and biochemical assays were primarily employed to assess changes in both senescence- and ferroptosis-related molecules in mouse hippocampal tissues in response to each treatment. Additionally, mouse hippocampal HT22 neuronal cell cultures were utilized to corroborate the in vivo findings.

Results: The targeted activation of ErbB4 receptor by E4A significantly ameliorated the behavioral deficits induced by D-gal in mice, demonstrating an effect comparable to that of melatonin, a natural inhibitor of in vivo senescence and ferroptosis. Both E4A and melatonin mitigated D-gal-induced aging in hippocampal neurons of mice. This was evidenced by the upregulation of Lamin B1 and the downregulation of P53, P21, P16, GFAP, and Iba-1 expression levels. Moreover, D-gal treatment markedly decreased the protein expression of the ferroptosis inhibitor Nrf2 while augmenting the expression of the ferroptosis promoter TFRC. These alterations were partially reversed by the individual administration of E4A and melatonin. In vitro studies further corroborated that D-gal treatment significantly and concurrently induced the expression of senescence markers and ferroptosis promoters. However, both E4A and melatonin were able to significantly reverse these changes. Additionally, E4A markedly ameliorated Erastin-induced ferroptosis in mouse hippocampal neuronal cells.

Conlusion: Our findings suggest that targeted activation of ErbB4 receptor may be a viable strategy for treating neuronal senescence by inhibiting ferroptosis, thereby offering a potential therapeutic avenue for senescence-associated neurodegenerative diseases.

Background: Growing reports are dedicated to providing novel agents for wound healing with fewer adverse effects and higher efficacy. The efficacy of nanofibers composed of polyvinyl alcohol (PVA)/polyethylene oxide (PEO)/chitosan (CS) in promoting wound healing can be attributed to their ability to stimulate collagen production. Among the herbal agents with fewer adverse effects, Tragopogon graminifolius DC. [Asteraceae] (TG), also called "Sheng" in traditional Iranian medicine, is one of the most efficacious plants for treating various skin injuries due to its several pharmacological and biological effects like anti-inflammatory and antioxidant properties.

Purpose: In the present study, our objective was to assess the wound-healing activity of PVA/PEO/CS nanofibers containing TG in a rat model of excision wound repair.

Methods: Synthesized nanofibers from PVA, PEO, and CS were done by the electrospinning method and confirmed by scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FT-IR). The release tests of nanofibers were assessed through the UV-visible method at different time intervals, which were conducted for about 60 h. To evaluate the wound healing effects, rats were divided into four distinct groups, including negative control (untreated), phenytoin cream (as positive control), polymer (PVA/PEO/CS), and drug (nanofiber-containing 50% of TG extract; named PVA/PEO/CS/TG) groups. All treatments were administered topically once daily for 14 days. Wound size changes were investigated in different time intervals. On the 15th day, nitrite and catalase serum levels were measured. Furthermore, samples of skin tissue were extracted and subjected to histopathological analysis.

Results: PVA/PEO/CS nanofibers containing 1.2 g of PVA, 0.3 g of PEO, and 0.8 g of CS, along with 50% of TG extract (PVA/PEO/CS/TG) at 17 kV were selected based on its favorable morphology and uniform quality. PVA/PEO/CS/TG represented a notable reduction in wound sizes. Moreover, in histopathological analysis, PVA/PEO/CS/TG showed a lower presence of inflammatory cells, higher density of dermis collagen fibers, and better regeneration of the epidemic layer. In addition, PVA/PEO/CS/TG elevated plasma antioxidant capacity via increasing catalase while reducing nitrite levels.

Conclusion: PVA/PEO/CS/TG is a promising wound dressing nanofiber with antioxidant and tissue regeneration potential. These results encourage further studies for the development of TG nanofibers as promising agents in treating and accelerating the process of excision wound repair.

Objective: This randomized controlled trial aims to evaluate the efficacy and safety of Yishenyangsui granule for treating Degenerative Cervical Myelopathy.

Materials and methods: A randomized, double-blind, placebo-controlled clinical trial was conducted with 152 participants recruited from three centers and randomly assigned to receive either Yishenyangsui granule or placebo. The Japanese Orthopaedic Association (JOA) score and Neck Disability Index (NDI) score were evaluated for 32 weeks. Patient-reported outcomes including surgical treatment data, re-treatment data, and patient-reported condition were collected for long-term follow-up. This trial was approved by the ethics committee of WangJing Hospital of China Academy of Chinese Medical Sciences (WJEC-KT-2016-004-P001) and was registered at the Chinese Clinical Trials Registry (ChiCTR-INR-16009723) on 03 November 2016 (Check out at https://www.chictr.org.cn/indexEN.html for a more comprehensive overview).

Results: The results showed that the improvement in JOA score at week 8 was significantly better in the Yishenyangsui granule group than in the placebo group (1.47 vs. 0.43; P < 0.001). Furthermore, improvements in motor function of upper/lower extremities, sensory function of upper extremities, reading ability, and recreation domain scores were also significantly superior in the Yishenyangsui granule group compared to the placebo group (P < 0.05). Long-term follow-up outcomes revealed no statistical differences between groups regarding surgical treatment data or patient-reported condition (P > 0.05). However, there was a significant difference detected in re-treatment data between groups with a lower rate observed among those receiving Yishenyangsui granule compared to those receiving placebo [25 (43.10%) vs. 40 (68.97%); P = 0.033], indicating its effectiveness for treating mild-to-moderate Degenerative Cervical Myelopathy.

Conclusion: Yishenyangsui granule was effective in treating mild to moderate Degenerative Cervical Myelopathy. The participants have improved long-term outcomes.

Clinical trials registration: https://www.chictr.org.cn/indexEN.html, identifier ChiCTR-INR-16009723.

Introduction: Parkinson's disease (PD) is a common neurodegenerative disorder primarily affecting motor function due to progressive loss of dopaminergic neurons in the substantia nigra. Current therapies offer symptomatic relief but fail to halt disease progression, highlighting the need for novel therapeutic strategies. This study explores the neuroprotective potential of exogenous human metallothionein 2 (hMT2) peptide in a rotenone-induced PD zebrafish model.

Methods: Adult zebrafish were divided into four groups: control, rotenone-treated, hMT2 pre-treatment, and hMT2 co-treatment. PD model was established by exposing zebrafish to 5 µg/L rotenone water for 28 days. hMT2 (0.2 µg) was administered intracranially either one day before or seven days after rotenone exposure.

Results: The novel tank test demonstrated that rotenone exposure significantly impaired locomotor activity (p < 0.05) and increased anxiety-like behavior (p < 0.001). Additionally, PD model zebrafish exhibited reduced dopamine levels, decreased dopaminergic neuron population, elevated oxidative stress, heightened inflammatory response and mitochondrial dysfunction. Treatment with hMT2, especially in the co-treatment group, ameliorated these deficits by restoring locomotor activity, dopamine levels, and dopaminergic neuron counts while reducing oxidative stress and inflammation, and improving mitochondrial function.

Discussion: These results suggest that hMT2 exhibited neuroprotective effect in the PD model zebrafish. These findings support the potential of MT as a therapeutic agent for PD.

This study explores the impact of metformin dosage and hyperprolactinemia on galectin-3 levels in women with Polycystic Ovary Syndrome (PCOS), providing novel insights into their roles in the metabolic and hormonal management of the condition. A cohort of 53 women, diagnosed using the Rotterdam criteria and undergoing in vitro fertilization (IVF) preparation, was analyzed to determine how these factors influence galectin-3, a biomarker in PCOS. Using high-performance liquid chromatography to measure metformin concentrations and ELISA for galectin-3, our results revealed that both metformin dosage and hyperprolactinemia significantly statistically associated with galectin-3 levels, while body mass index (BMI) showed no significant association. These findings challenge prior assumptions and suggest that galectin-3 may be regulated via pathways independent of metformin pharmacokinetics. Notably, the correlation between galectin-3 levels and metformin concentration was either absent or weak after adjusting for the daily dose, indicating that treatment duration and dosage, rather than absolute drug levels, may more critically influence galectin-3. This study offers deeper insights into the role of personalized metformin dosing in managing PCOS, enhancing the understanding of metabolic and hormonal regulation in this condition, and laying the groundwork for future targeted therapies.