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Background: No Fourier transform infrared (FTIR) spectroscopy studies have directly evaluated adrenalectomy vessels, the technique's established ability to probe collagen/elastin-associated spectral features and lipid peroxidation-related signatures, and protein structural damage. Stable gastric pentadecapeptide BPC 157 therapy was found to maintain the vascular function under severe stress, as FTIR spectroscopy recently demonstrated rapid peptide-induced molecular changes in healthy rat blood vessels, particularly in lipid content and protein secondary structure. Methods: To extend these findings and highlight the BPC 157 vascular background in the special circumstances of the course following unilateral adrenalectomy, abdominal aortas were collected at 15 min, 5 h, and 24 h after unilateral adrenalectomy for the FTIR spectroscopy assessment. Results: FTIR spectra were acquired, preprocessed, and analyzed using principal component analysis (PCA), support vector machine discriminant analysis (SVMDA), and band-specific statistics. BPC 157 (10 ng/kg intragatrically immediately after unilateral adrenalectomy) produced a clear, reproducible separation of aortic spectra from control samples at all time points. The main discriminatory spectral signatures were observed in three regions, including amide I and amide II (protein-related bands, consistent with collagen/elastin contributions) and lipid C-H stretching bands. These spectral signatures are consistent with early extracellular matrix reinforcement and membrane preservation in the vascular wall and align with the recovering effect on the lesions in counteraction of the severe vascular and multiorgan failure, attenuation/elimination of thrombosis and blood pressure disturbances in various occlusion/occlusion-like syndromes. Conclusions: Together, after unilateral adrenalectomy, the FTIR data provide molecular-level spectral signatures consistent with rapid remodeling of the aortic wall toward a more structurally stable and functionally favorable state.

Background/Objectives: Pyrus ussuriensis Maxim. has been cultivated in many regions worldwide. This plant is also regarded as a profitable fruit crop for the development of many food and functional products. There is limited research on the application of the LC-MS associated reaction method for screening active compounds. In this study, we developed an analytical technique employing an ultra-high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI-MS/MS) system. Methods: The metabolite annotation procedure was used to interpret and validate data analysis via spectral matching against public databases. Results: As a result, metabolites from P. ussuriensis water and EtOH extracts were identified, and their quantities were further evaluated. The established method was employed to determine antioxidant capacity using a pre-incubation UHPLC-2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, thereby identifying antioxidant ingredients. The antioxidative interference of active constituents was predicted by calculating the decrease in the peak areas of the chemical composition detected in chromatograms between treated and non-treated samples. Furthermore, drug-likeness was also assessed via pharmacokinetics (absorption, distribution, metabolism, and excretion: ADME) evaluation. Conclusions: The online UHPLC-MS-DPPH method would be a powerful tool for the rapid characterization of antioxidant ingredients in plant extracts. The current study highlights the value of P. ussuriensis for improved health benefits.

Background/Objectives: SA001, a mofetil-ester prodrug of rebamipide, was developed to enhance gastrointestinal absorption and systemic exposure, which was confirmed in a prior Phase 1 study. Given the limited efficacy of current symptomatic therapies for primary Sjögren's syndrome (pSS), this trial aimed to assess whether the improved bioavailability of SA001 could translate into clinical benefits. Methods: This multicenter, randomized, double-blind, placebo-controlled Phase 2a study enrolled adults who met the 2016 ACR-EULAR criteria for pSS. The participants were randomly assigned to one of four groups: SA001 at 360, 720, or 1080 mg/day (administered twice daily for 8 weeks) or placebo. Exploratory ocular assessments included tear break-up time, ocular surface staining, the Schirmer test, and the Standard Patient Evaluation of Eye Dryness. Oral endpoints included unstimulated whole salivary flow and the Xerostomia Inventory. Anti-SSA(Ro) antibodies were assessed both quantitatively and qualitatively. Safety evaluations comprised adverse events (AEs), ophthalmic examinations, laboratory tests, and vital signs. The efficacy outcomes were exploratory, and this study was not powered to formally test efficacy hypotheses. Results: Twenty-eight women (mean age 58.54 ± 9.29 years; range 41-75 years) were enrolled in this study and randomly assigned to one of the study groups. SA001 showed no statistically significant improvements versus placebo in ocular or oral endpoints, and no consistent dose-response relationship was observed. The anti-SSA(Ro) findings did not differ meaningfully across the groups. SA001 was generally well-tolerated, with infrequent, mostly mild-to-moderate AEs; however, one serious AE occurred in the placebo group. No clinically relevant ophthalmic or laboratory safety signals were detected. Conclusions: Despite the fact that markedly increased systemic exposure has been demonstrated previously, SA001 did not improve the dryness outcomes in pSS. These findings suggest that systemic exposure alone may be insufficient in established glandular disease and highlight the need for tissue-exposure-driven strategies and biomarker-informed patient selection in future studies. Predefined primary efficacy endpoints and objective, gland-proximal measures of target engagement (e.g., standardized salivary gland ultrasonography and salivary or tear fluid biomarker assessments) may help to better interpret local pharmacodynamic activity and the likelihood of a clinically meaningful benefit.

Background: Vasicine (Vas) is a quinazoline alkaloid derived from Adhatoda vasica Nees, which has good anti-allergic asthma and anti-inflammatory effects. However, its specific functional mechanism on allergic asthma is unclear. This study aims to investigate the protective effect of Vas on allergic asthma and its underlying mechanisms. Methods: Initially, the therapeutic effects of Vas were assessed in ovalbumin-sensitized BALB/c mice using airway hyperresponsiveness (AHR), histopathological examinations, immunohistochemistry, and enzyme-linked immunosorbent assays (ELISA). Subsequently, a non-targeted metabolomic analysis was performed to examine the influence of Vas on lung metabolites, while molecular docking was utilized to clarify the mechanisms by which Vas intervenes in allergic asthma. Lastly, RBL-2H3 cells were employed in vitro to validate the metabolomic findings by measuring intracellular Ca²⁺ concentrations, in addition to conducting ELISA and Western blot analyses. Results: In vivo, Vas alleviates AHR in mice with allergic asthma, enhances histopathological conditions, and reduces inflammatory factors. Non-targeted metabolomics analyses indicate that the primary pathway implicated in its intervention in allergic asthma may be the FcεRI pathway. Furthermore, molecular docking techniques were utilized to evaluate the binding affinity between Vas and proteins associated with this pathway. In vitro, Vas effectively inhibits degranulation in RBL-2H3 cells and diminishes the release of inflammatory factors by modulating the FcεRI/Lyn + Syk/MAPK pathway. Conclusions: These findings indicate that Vas may effectively alleviate allergic asthma by reducing inflammatory responses, decreasing AHR, and improving histopathological features. Furthermore, Vas seems to inhibit mast cell degranulation and modulate the FcεRI/Lyn + Syk/MAPK pathway.

Background: Ganoderma lucidum triterpenes are bioactive compounds with recognized anti-inflammatory, antitumor, and immunomodulatory properties. This systematic review synthesizes evidence regarding the anti-inflammatory activity of these triterpenes based on studies from the last two decades. Methods: A systematic search was performed in PubMed, Medline, and Embase (2003-2025) for original in vitro and in vivo (non-clinical) studies evaluating G. lucidum triterpene extracts or isolated compounds. Clinical trials, reviews, and multi-species extracts were excluded. The review is registered on PROSPERO (CRD42024510982), and animal study quality was assessed using the SYRCLE Risk of Bias tool. Findings: From over 3000 records, 23 articles were included. Studies utilized diverse models, including macrophages, human PBMCs, and various animal strains (mice, rats, chickens). All studies reported significant anti-inflammatory effects via reduction in pro-inflammatory markers (TNF-α, IL-1β, IL-6), primarily through downregulation of MAPK and TLR-4/NF-κB signaling pathways. Meta-analysis of in vitro data confirmed significant reductions in NO levels (-3.29 [95% CI: -5.21, -1.37]; p = 0.0008), IL-6 (-3.51 [-4.73, -2.29]; p < 0.00001), and TNF-α (-2.20 [-2.93, -1.48]; p < 0.00001). Similar anti-inflammatory profiles were observed in vivo across hepatic and splenic tissues. Interpretation: Evidence consistently demonstrates the potent anti-inflammatory activity of G. lucidum triterpenes, highlighting their potential as therapeutic candidates for inflammatory diseases. However, the structural complexity and isomer diversity of these compounds remain significant barriers to pharmacological standardization. Future research must prioritize clinical translation by investigating compound synergism, bioavailability, and long-term toxicity profiles, which were notably absent in current non-clinical literature.

Cancer remains a significant challenge in the field of medicine, primarily due to its inherent plasticity and the development of resistance to conventional therapeutic interventions. Genomic mutations and the activation of oncogenes enable cancer cells to resist senescence and apoptosis, leading to uncontrolled growth with harmful consequences. Small peptides are molecules with interesting anti-tumour properties and represent a valid alternative to conventional treatments. Our group has previously identified a class of small peptides bound to the DNA that can be extracted from the chromatin of various tissues, including wheat germ and trout. These peptide pools have been shown to possess interesting antiproliferative and apoptotic properties, and they are associated with cell cycle regulation. However, given the complexity of the extraction process, it is necessary to identify a substrate that will enable a more efficient extraction of these peptides, while also ensuring a composition that is simple to investigate. The present study developed a method for the extraction of this group of peptides from yeast, and the extract was then tested on cancer cells in order to confirm its anti-tumoral properties. The peptides were obtained from chromatin extracted from Saccharomyces cerevisiae cells through alkalisation and purification by gel filtration chromatography. The extract was tested on HeLa cells to verify its effects on vitality and the cell cycle. The data demonstrate that the chromatographic profile of this peptide extract indicates a more basic composition than the pool extracted from other tissues and exhibits comparable antiproliferative properties. The ability to rapidly obtain a biologically active, analytically accessible, and adequately purified fraction from the widely available substrate Saccharomyces cerevisiae represents a significant advance in the study of these DNA-binding peptides.

Background/Objectives: Diabetes is characterized by multiple metabolic disorders, defined by high blood sugar levels over a prolonged duration. Type 2 diabetes (T2D) comprises defective insulin secretion, its ineffective utilization, or both, resulting in hyperglycemia. The disease is one of the leading causes of mortality, according to the WHO, and necessitates the development of advanced therapeutics. Methods: This systematic review was conducted in accordance with the PRISMA guidelines. The study and execution of the literature review followed a timeframe of 3-6 months, during which the conceptualization, execution, analysis, writing, and editing were conducted. Ginsenosides, triterpenoids from the Panax genus, are widely recognized for their promising antidiabetic effects, mediated through mechanisms that include glucose uptake, insulin secretion, antioxidant activity, and anti-inflammatory pathways. Ongoing clinical trials in patients with IGT or Type 2 diabetes have shown an improvement in insulin sensitivity and glucose control, and consolidate the therapeutic potential of ginseng pharmacotherapy. Results: This viewpoint summarizes the most recent discoveries on the hypoglycemic mechanisms of ginsenosides for Type 2 diabetes and its associated complications, with a major focus on ginseng-based drug development. An emphasis is placed on how ginsenosides control blood glucose levels and regulate signaling pathways, investigating their antidiabetic mechanisms and potential. Conclusions: Preclinical studies suggest that nano-innovations in ginseng have the potential to address therapeutic challenges, improve systemic circulation, lower the toxicity of biomolecules, and improve bioavailability, defining exciting outcomes. Furthermore, well-designed human clinical trials are necessary to understand the antidiabetic mechanisms and pharmacological potential of ginseng and/or ginsenosides in drug development.

Background/Objectives: Cutaneous leishmaniasis (CL) remains a major neglected tropical disease, and current chemotherapeutic options are limited by toxicity and emerging resistance. Repurposing azole antifungals is a promising approach, as they target ergosterol biosynthesis, a pathway also essential in Leishmania spp. This study investigated the antileishmanial potential of econazole through in vitro and in vivo assays. Methods: Econazole activity was evaluated against Leishmania amazonensis promastigotes and intracellular amastigotes using MTT and luminescence-based methods. Cytotoxicity in NCTC cells was determined to calculate the selectivity index (SI). Drug interactions with miltefosine were assessed by fixed-ratio isobologram analysis. In vivo efficacy was examined in BALB/c mice infected with L. amazonensis and orally treated with econazole (2.5, 5, or 10 mg/kg/day) for 28 days. Lesion development and parasite burden were monitored. Molecular docking simulations were performed using SwissDock. Results: Econazole showed potent in vitro activity, with EC₅₀ values of 8.9 µM for promastigotes and 11 µM for intracellular amastigotes, and a CC₅₀ of 31 µM. Isobologram analysis revealed additive interactions with miltefosine (ΣFIC 0.5-1.2; mean 0.95). In vivo, econazole reduced lesion size and parasite load, achieving up to 75% reduction at 10 mg/kg/day. Docking results suggested that econazole may inhibit sterol biosynthesis, potentially through interaction with 14α-demethylase. Conclusions: These findings provide the first evidence of econazole activity against L. amazonensis in vitro and in vivo. Its exploratory efficacy and compatibility with miltefosine support further investigation of econazole as a repurposed candidate for CL, including optimization of dosing strategies and combination regimens.

Objectives: This study evaluated the effects of modified Gamchogeongang-tang (GGS01) on lung injury using a COPD mouse model. Methods: C57BL/6 mice were exposed to cigarette smoke extract and lipopolysaccharide and treated with GGS01 (100, 200, or 400 mg/kg). Bronchoalveolar lavage fluid (BALF) and lung tissue were analyzed using cytospin, enzyme-linked immunosorbent assay, real-time polymerase chain reaction (PCR), flow cytometry analysis, hematoxylin and eosin (H&E) and Masson's trichrome staining, and immune histology fluorescent staining. Results: GGS01 significantly inhibited the increase in neutrophils in BALF, decreased immune cell activity in BALF and lung tissue, and inhibited the increase in the levels of IL-1α, TNF-α, IL-17A, MIP2, and CXCL-1 in BALF. Conclusions: Real-time PCR analysis showed that MUC5AC mRNA expression in lung tissue significantly decreased compared with the control group. The score of histological analysis of lung tissue damage was significantly reduced, and a decrease in IRAK1 and TNF-α expression in lung tissue was observed.

Cardiovascular disease (CVD) remains a leading cause of global morbidity and mortality, and its initiation and progression are closely associated with multiple molecular mechanisms. Neutrophil extracellular traps (NETs) are mesh-like structures composed of DNA, histones, and antimicrobial proteins that are released by neutrophils during inflammation or infection. They play a crucial role in innate immune defense. However, when the dynamic balance of NETs is disrupted by excessive formation, persistent accumulation, or impaired clearance, NETs are no longer merely bystanders. Instead, they actively drive pathological processes in multiple CVDs and serve as a critical link between inflammation and cardiovascular injury. Given the central role of NETs in CVD pathogenesis, including atherosclerosis, myocardial ischemia-reperfusion injury, pulmonary arterial hypertension, atrial fibrillation, and heart failure, therapeutic strategies targeting NETs, such as inhibiting aberrant formation, enhancing clearance, or neutralizing toxic components, have emerged as promising approaches. In recent years, traditional Chinese medicine (TCM) and natural products have shown potential therapeutic value by modulating NET formation and promoting NET degradation, owing to their multitarget, multipathway regulatory effects. This article reviews the mechanisms by which NETs operate in CVDs and explores potential pathways through which TCM and natural active ingredients prevent and treat CVDs by regulating NETs. This review provides theoretical support for further research and clinical application.