Search Results (3,272)

Cholesterol plays a fundamental role in the human body—it stabilizes cell membranes, modulates gene expression, and is a precursor to steroid hormones, vitamin D, and bile salts. Its correct level is crucial for homeostasis, while both excess and deficiency are associated with serious metabolic and health consequences. Excessive accumulation of cholesterol leads to the development of atherosclerosis, while its deficiency disrupts the transport of fat-soluble vitamins. Magnetic resonance spectroscopy (MRS) enables the detection of cholesterol esters and the differentiation between their liquid and crystalline phases, but the technical limitations of clinical MRI systems require the use of dedicated coils and sequence modifications. This study demonstrates the feasibility of using MRS to identify cholesterol-specific spectral signatures in atherosclerotic plaque through ex vivo analysis. Using a custom-designed experimental coil adapted for small-volume samples, we successfully detected characteristic cholesterol peaks from plaque material dissolved in chloroform, with spectral signatures corresponding to established NMR databases. To further enhance spectral quality, a deep-learning denoising framework based on a 1D U-Net architecture was implemented, enabling the recovery of low-intensity cholesterol peaks that would otherwise be obscured by noise. The trained U-Net was applied to experimental MRS data from atherosclerotic plaques, where it significantly outperformed traditional denoising methods (Gaussian, Savitzky–Golay, wavelet, median) across six quantitative metrics (SNR, PSNR, SSIM, RMSE, MAE, correlation), enhancing low-amplitude cholesteryl ester detection. This approach substantially improved signal clarity and the interpretability of cholesterol-related resonances, supporting more accurate downstream spectral assessment. The integration of MRS with NMR-based lipidomic analysis, which allows the identification of lipid signatures associated with plaque progression and destabilization, is becoming increasingly important. At the same time, the development of high-resolution techniques such as μOCT provides evidence for the presence of cholesterol crystals and their potential involvement in the destabilization of atherosclerotic lesions. In summary, nanotechnology-assisted MRI has the potential to become an advanced tool in the proof-of-concept of atherosclerosis, enabling not only the identification of cholesterol and its derivatives, but also the monitoring of treatment efficacy. However, further clinical studies are necessary to confirm the practical usefulness of these solutions and their prognostic value in assessing cardiovascular risk. Full article

There are a vast number of monoclonal antibodies (MAbs) against biological components; however, the number for natural products is less than 50. MAbs against ginsenosides, i.e., dammarane triterpene glycosides contained in ginseng, were prepared to develop an Eastern blotting method that can estimate the number of bound sugars and pharmacological activity. Meanwhile, as a method for producing ginsenoside Rg3, which is used as an anti-cancer drug, an affinity column for ginsenoside Rb1 was prepared to isolate the raw material ginsenoside Rb1 in a single step, and a method for obtaining ginsenoside Rg3 through fermentation was proposed. A unique MAb capable of detecting all solasodine glycosides contained in Solanum plants was created to prepare an affinity column capable of isolating solasodine glycosides from S. khasianum fruit in a single step. The single-chain variable fragment gene was induced from the MAb against solasodine glycoside and introduced into the hairy root system of S. khasianum, thereby increasing the solasodine glycoside content more than twofold. As a result, we recognized that this method can be used to breed plants with higher concentrations of plant secondary metabolites like solasodine glycosides. The above results collectively demonstrate that solasodine glycoside can be isolated from S. khasianum in high yields and that this compound enables the production of steroids in high yields through a one-step chemical reaction. Full article

Background: Metabolic reprogramming is increasingly recognized as a hallmark of endometrial cancer, yet tissue-based metabolic signatures remain insufficiently defined. Methods: Untargeted metabolomics was performed on paired endometrial cancer (n = 10) and adjacent normal tissues (n = 10). Differential metabolites were identified through multivariate and univariate analyses. KEGG enrichment characterized altered pathways, while Random Forest and SVM were used for machine-learning-based feature prioritization. ROC analyses were conducted to evaluate the discriminative potential of selected metabolites. Results: 300 metabolites were significantly altered. Tumor tissues showed increased sphingolipid metabolism, glutathione metabolism, and arachidonic acid metabolism, alongside decreased bile acid, phenylalanine, and steroid biosynthesis. Machine learning converged on six key metabolites that demonstrate strong tissue-discriminative capacity. Conclusions: Endometrial cancer exhibits a distinct metabolic profile characterized by lipid remodeling and redox adaptation. The six metabolites identified through machine-learning-based analyses represent candidate metabolic features associated with endometrial cancer and provide a foundation for future mechanistic studies and validation in larger, independent cohorts. Full article

Zearalenone (ZEA) is a mycotoxin commonly found in animal feed and is associated with pronounced reproductive toxicity. However, most studies on ZEA’s reproductive effects have focused on female monogastric animals, while research on male ruminants remains limited. This study aimed to investigate the cytotoxic and metabolic mechanisms underlying ZEA-induced damage in goat Leydig cells (LCs). The CCK8 assay was first used to determine the effective ZEA concentration (IC₅₀ ≈ 20 μM), and a cytotoxicity model was subsequently established. The model’s validity was confirmed using qRT-PCR, transmission electron microscopy, flow cytometry, and JC-1 staining. Results showed that ZEA significantly reduced LCs viability in a dose-dependent manner, decreased mitochondrial membrane potential, induced cell cycle arrest, and triggered apoptosis. Targeted and untargeted metabolomics analyses revealed that ZEA disrupts steroidogenic pathways and alters steroid hormone secretion, resulting in elevated levels of progesterone, corticosterone, and androstenedione, and reduced dihydrotestosterone levels. Furthermore, 52 significantly altered metabolites were identified, predominantly enriched in glycerophospholipid metabolism, choline metabolism, and neurotransmitter vesicle pathways, with corresponding changes in gene expression. Collectively, this study has confirmed that ZEA causes harm to the reproductive cells of male goats in multiple aspects, underscoring the link between metabolic dysregulation and reproductive impairment, and offering a foundation for evaluating ZEA’s impact on goat reproductive performance. Full article

Obesity is closely linked to dyslipidemia, hepatic injury, and chronic inflammation through disturbances in the gut–liver axis. Here, we evaluated the anti-obesity effects of L. rhamnosus (Lacticaseibacillus rhamnosus) CU262 in a high-fat diet (HFD) mouse model and elucidated mechanisms using an integrated multi-omics strategy. Male C57BL/6 mice received CU262 during 12 weeks of HFD feeding. Phenotypes, serum/liver biochemistry, gut microbiota (16S rRNA sequencing), fecal short-chain fatty acids (SCFAs), and hepatic transcriptomes (RNA-seq) were assessed. CU262 significantly attenuated weight gain and adiposity; improved serum TC, TG, LDL-C and HDL-C; lowered ALT/AST and FFA; and mitigated oxidative stress and inflammatory imbalance (↓ IL-6/TNF-α, ↑ IL-10). CU262 restored alpha diversity, reduced the Firmicutes/Bacteroidetes ratio, enriched beneficial taxa (e.g., Akkermansia), and increased acetate and butyrate. Liver transcriptomics showed CU262 reversed HFD-induced activation of cholesterol/steroid biosynthesis and endoplasmic reticulum stress, with downregulation of key genes (Mvk, Mvd, Fdps, Nsdhl, and Dhcr7) and Pcsk9, yielding negative enrichment of steroid and terpenoid backbone pathways and enhancement of oxidative phosphorylation and glutathione metabolism. Correlation analyses linked Akkermansia and SCFAs with improved lipid/inflammatory indices and repression of cholesterol-synthetic and stress-response genes. These findings demonstrate that CU262 alleviates HFD-induced metabolic derangements via microbiota-SCFA-hepatic gene network reprogramming along the gut–liver axis, supporting its potential as a functional probiotic for obesity management. Full article

Background/Objectives: The optimal duration of pulsed radiofrequency (PRF) applied to the dorsal root ganglion (DRG) remains unclear, particularly in patients with chronic lumbosacral radicular pain (LRP) who are unresponsive to conservative therapy. Although preclinical data suggest duration-dependent neuromodulatory effects, comparative clinical evidence for specific exposure times is limited. This study aimed to evaluate the outcomes of 4 min and 8 min DRG-targeted PRF applications performed in combination with transforaminal epidural steroid injection (TFESI) in patients with chronic LRP unresponsive to conservative treatment, to determine whether prolonged exposure provides superior analgesic and functional outcomes. Methods: In this prospective, single-center, observational comparative study, 72 patients with chronic lumbar radicular pain (LRP) refractory to conservative management received DRG-targeted PRF using standardized parameters (45 V, 20 ms, 2 Hz, ≤42 °C). Participants underwent either 4 min (n = 36) or 8 min (n = 36) PRF, assigned according to clinical discretion. All procedures were followed by transforaminal epidural injection of dexamethasone and bupivacaine. The primary endpoint was Numeric Rating Scale (NRS) pain intensity at 6 months. Secondary endpoints included Oswestry Disability Index (ODI), patient satisfaction, responder rates, and analgesic use across 1-, 3-, and 6-month follow-up. Results: Both groups achieved significant improvements from baseline at all time points. Linear mixed-effects analysis demonstrated a significant overall association favoring the 8 min protocol for pain (estimate: −0.81, 95% CI: −1.52 to −0.10, p = 0.025) and functional disability (estimate: −12.84, 95% CI: −19.36 to −6.32, p < 0.001). Functional benefits emerged by 3 months (p = 0.006), while pain reduction reached borderline statistical significance at 6 months (p = 0.048). The 8 min group showed numerically higher responder rates and patient satisfaction without increased adverse events. Conclusions: In this study evaluating a combined PRF and corticosteroid injection protocol, 8 min PRF exposure was associated with superior pain and functional outcomes compared to 4 min, without compromising safety. However, the observational design and concurrent medication administration limits causal inference. Randomized controlled trials are needed to confirm these findings and isolate the independent effect of PRF duration. Full article

Background: Chronic nonbacterial prostatitis (CNP), the major subset of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), imposes a substantial global burden yet lacks satisfactory therapies. Maizibizi Wan (MZBZ) has long been used clinically for prostatitis, but its pharmacodynamic substance basis and mechanisms remain unclear. Methods: Ultra-high-performance liquid chromatography–Q-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS) coupled with Global Natural Products Social Molecular Networking (GNPS) molecular networking profiled MZBZ constituents and rat plasma–exposed prototype components and metabolites was used. Based on blood-absorbable components, network pharmacology predicted core targets/pathways; representative interactions were validated by molecular docking. A λ-carrageenan–induced CNBP rat model underwent histopathology (H&E), serum cytokine assays (TNF-α, IL-1β, IL-6/IL-17), immunohistochemistry (COX-2, TNF-α, MMP-9), and Western blotting (P-p65/p65, p-AKT/AKT, COX-2, TGF-β1, BCL2). Results: A total of 188 chemical constituents were identified in MZBZ (79 flavonoids, 38 organic acids, 30 alkaloids, 15 phenylpropanoids, 7 steroids, 4 phenylethanoid glycosides, 15 others). A total of 35 blood-absorbable components (18 prototype components, 17 metabolites) were identified, mainly involving Phase I oxidation and Phase II glucuronidation/sulfation. Network analysis yielded 54 core targets enriched in NF-κB and PI3K/AKT signaling and apoptosis. Docking indicated stable binding of key flavonoids to COX-2, NFKB1, TNF, IL-6, and BCL2. In vivo, MZBZ ameliorated prostatic inflammation, reduced serum TNF-α/IL-1β/IL-6/IL-17 (p < 0.05 or p < 0.01); decreased P-p65/p65, p-AKT/AKT, COX-2, and TGF-β1; and increased BCL2 in prostate tissue. Conclusions: MZBZ exerts anti-CNBP effects via multi-component synergy (prototypes + metabolites) that suppresses inflammatory cytokines, modulates apoptosis, and inhibits NF-κB and PI3K/AKT pathways. These findings provide a mechanistic basis and quality control cues for the rational clinical use of MZBZ. Full article

Background: Tribulus terrestris (Tt) is a popular herbal supplement marketed to enhance fitness performance, despite inconclusive evidence regarding its efficacy and safety. This study aimed to investigate the prevalence of TT use, awareness, and motivations for its use among recreational athletes in Italy, helping to address the lack of empirical data describing who actually uses Tt, for what purposes, and with what behavioral risks. Methods: A cross-sectional anonymous survey was administered between May and October 2024 across Italian gyms and fitness clubs using Microsoft Forms. A total of 696 individuals initiated the questionnaire; after removal of duplicate, incomplete and ineligible entries, 510 responses were analyzed. Two indicators of Tt consumption were assessed: ever use and current use, with the latter designated as the primary outcome. A multivariable logistic regression evaluated predictors of current Tt use, entering sex, age category (18–24, 25–34, 35–44, ≥45 years), and motivation for supplement consumption. Results: Current Tt use was reported by 7.8% of respondents, while 10.5% declared ever using a Tt-containing product. Motivation was the only independent predictor of Tt consumption (p = 0.012). Individuals reporting performance enhancement as their primary motivation were markedly more likely to currently use Tt, compared with those using supplements for other purposes (adjusted OR ≈ 18.5; p = 0.008). Neither sex (p = 0.918) nor age category (p = 0.519) significantly predicted Tt use. Admission of anabolic steroid use was infrequent but was linked to online purchasing from potentially unregulated sources. Conclusions: Tt consumption in fitness settings is driven predominantly by performance-oriented expectations rather than demographic characteristics. The observed discrepancy between consumer beliefs and scientific evidence suggests a pressing need for educational interventions and regulatory vigilance in sports nutrition. Public health policies should focus on improving label literacy, strengthening consumer protection, and countering misinformation within supplement marketing environments. Full article

Wound dressing coverages (WDC) play a key role in protecting skin lesions and preventing infection. Polymeric membranes have been widely explored as WDC due to their ability to incorporate bioactive agents, including antimicrobial nanoparticles and non-steroidal anti-inflammatory drugs (NSAIDs). In this study, polycaprolactone (PCL)-based membranes functionalized with titanium dioxide nanoparticles (TiO₂ NPs) and ibuprofen (IBP) were fabricated using a film manufacturing approach, and their structural and biocompatibility profiles were evaluated. The membranes were characterized by SEM, FTIR and XPS. Bands at 1725 cm⁻¹, 2950 cm⁻¹, 2955 cm⁻¹, 2865 cm⁻¹ and 510 cm⁻¹ proved molecular stability of reagents during manufacture. In SEM, the control shows the flattest surface, while the PCL-IBP and PCL-IBP-TiO₂ NPs groups had increased rugosity. In vitro biocompatibility was evaluated using human fetal osteoblasts (hFOB). On day 3, the cell adhesion response of hFOB seeded in PCL-IBP and PCL-IBP-TiO₂ NPs groups showed the biggest absorbances (p = 0.0014 and p = 0.0491, respectively). On day 7 PCL-IBP group had lower lectin binding than the control (p = 0.007) and the PCL-IBP-TiO₂ NPs (p = 0.015) membranes, but no evidence of cytotoxicity was observed in any group. Furthermore, the Live/Dead test adds more biocompatibility evidence to conveniently discriminate between live and dead cells. The PCL polymeric membrane elaborated in this study may confer antiseptic, analgesic and anti-inflammatory properties, making these membranes ideal for skin lesions. Full article

Background/Objective: Nasal pressure injuries following non-invasive ventilation (NIV) have remained a common complication. Available evidence on injury severity characteristics, timing, and predictors of progression to moderate–severe injury, especially in large cohorts, is limited. The objective was to assess the incidence, characteristics and risk factors for nasal pressure injuries among neonates on NIV in a large tertiary neonatal intensive care unit (NICU). Methods: This retrospective observational study recruited all infants who experienced nasal pressure injury while on NIV from March 2018 to November 2022. The severity of the injury was categorized by the Fischer classification. Demographics, perinatal, respiratory, and device-related factors were examined. Multivariable logistic regression revealed independent predictors of moderate to severe injury. Results: There were 237 nasal injury episodes in 226 infants (0.406 per 100 device-days), considering 17,004 NICU admissions and 58,363 NIV device-days. Most injuries were mild (Stage I 81%) while 19% were moderate–severe (Stage II–III). Early injuries (≤3 days after NIV) were present in 83.5% of patients and were often related to the nasal bridge. In particular, late-onset injuries (>3 days) were more likely in infants with previous injury, exposure to postnatal steroids, longer prior intubation, or septal involvement. Moreover, multivariable analysis identified three specific independent predictors of moderate–severe injury previous nasal injury (aOR 6.25, 95% CI 1.11–35.35), septal or combined bridge/septum involvement (aOR 2.98, 95% CI 1.04–8.43), and prolonged period of positive pressure ventilation at birth (aOR 1.23 per minute, 95% CI 1.04–1.45). Conclusions: Most nasal pressure injuries seen during NIV are mild and early; however, recurrence, septal involvement, and prolonged resuscitative ventilation markedly increase the risk of severe injury. Improving surveillance on early NIV use, monitoring of septal pressure points, and proactive interventions with interface management will aid in minimizing preventable nasal morbidity. Full article

Background: Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy where endogenous steroid excess may foster immune evasion. However, whether this hormonal axis directly modulates the antigen presentation machinery remains unclear. Methods: We applied an immunoinformatics approach to the TCGA-ACC cohort (n = 79) to investigate relationships among steroid phenotype, HLA expression, tumor microenvironment (TME), and patient outcome. Key findings were assessed in an independent validation cohort (ENSAT-ACC, n = 44) using C1A/C1B molecular subtypes corresponding to the steroid phenotypes. Results: Stratification by steroid phenotype revealed two distinct immunological profiles. The high steroid production (HSP) phenotype was associated with suppressed HLA expression and a lymphocyte-depleted “cold” TME. In contrast, the low steroid production (LSP) phenotype displayed elevated HLA expression, enriched T-cell infiltration, and upregulation of immune checkpoints (e.g., PDCD1, CTLA4), consistent with an inflamed but exhausted TME. The core signature of HLA downregulation in the HSP-like phenotype (C1A) and the significant survival advantage of the LSP-like phenotype (C1B) were confirmed in the validation cohort, demonstrating biological robustness despite platform and sample size differences. Conclusions: These findings identify the steroid phenotype as a critical regulator of immune escape in ACC. Our results support incorporating this stratification as a biomarker for patient selection, identifying LSP tumors as the subgroup most likely to benefit from immune checkpoint blockade due to their “hot” yet exhausted microenvironment. Full article

Background: Emerging evidence suggests that lipedema may share hormonal, inflammatory, and genetic mechanisms with gynecologic diseases, particularly endometriosis. However, the extent and nature of these interrelationships remain poorly characterized, supporting the need for this scoping review. Objectives: To map and synthesize the available evidence on the clinical, pathophysiological, and epidemiological interrelationships between lipedema in women, endometriosis, and other gynecologic diseases. Methods: Searches were conducted in international and regional health databases, including MEDLINE (PubMed), CINAHL, Scopus, Embase, Web of Science, the Cochrane Library, LILACS/VHL, APA PsycInfo, SciELO, Epistemonikos, and La Referencia, as well as grey literature sources and relevant institutional websites. There were no language restrictions. The search period began in 1940, the year in which lipedema was first described by Allen and Hines. Study selection followed a two-stage process conducted independently by two reviewers, consisting of title and abstract screening followed by full-text review. Data extraction was performed using a pre-developed and peer-reviewed instrument covering participants, concept, context, study methods, and main findings. The review protocol was registered in the Open Science Framework. Results: Twenty-five studies from ten countries were included. Synthesized evidence supports the characterization of lipedema as a systemic condition with metabolic and hormonal dimensions. Key findings include symptom onset linked to reproductive milestones, a high frequency of gynecologic and endocrine comorbidities, and molecular features overlapping with steroid-dependent pathologies. These patterns reflect a recent shift from a predominantly lymphovascular paradigm toward a more integrated endocrinometabolic framework. Conclusions: The findings indicate that lipedema clusters with hormone-sensitive gynecologic and endocrine features across reproductive life stages. Full article

Tropical almond tree (Terminalia catappa L.), belonging to the Combretaceae family, is an unfurling tree with different edible parts. This review discussed the nutritional content, ethnopharmacological applications, main bioactive components, biological effects and economic potential of T. catappa. T. catappa shows essential applications in medicine, cosmetics and pharmaceutics. The nutritional values of T. catappa are associated with its contents of carbohydrates, minerals, proteins, lipids, vitamins and amino acids. It is used in many ethnopharmacological applications, including a heart stimulator, anti-diarrhoeal, bactericidal, anti-parasitic and anti-stress. T. catappa is used to treat angina pectoris, asthma attacks and bronchitis. The main reported biological activities for T. catappa were antioxidant, antidiabetic, anti-atherosclerosis, antitumor, antimicrobial, anthelmintic, antimalaria, hepatoprotective, insecticidal, anti-inflammatory and antihyperlipidemic activities. The main bioactive components reported in T. catappa encompassed phenolic compounds, alkaloids, diterpenes, fatty acids, galloyl glucose and derivatives, steroids and coumarins. T. catappa shows great economic opportunities which need to be expanded and diversified, taking into account its sustainability. Full article

Grain feeding is used to alleviate grazing pressure on the Tibetan Plateau. This study employed metabolomics and transcriptomics to elucidate the regulatory mechanisms of grain feeding on yak (Bos grunniens) meat quality, intramuscular fat, and amino acids. The results demonstrate that grain feeding significantly reduces meat shear force (11.05 vs. 18.98) and increases intramuscular fat content (1.48 g/100 g vs. 0.75 g/100 g). This is accompanied by elevated levels of monounsaturated and saturated fatty acids, alongside a decreased proportion of n-3 PUFAs, leading to a higher n-6/n-3 ratio of 5.13. Mechanistically, metabolomic analysis identified 83 differential metabolites, including flavor-related nucleosides, amino acids, and key lipids, such as palmitoleic and oleic acid, which collectively contribute to improved flavor and tenderness. Concurrently, transcriptomics revealed 1047 differentially expressed genes enriched in lipid metabolism pathways, including PPAR signaling, steroid biosynthesis, and glycerolipid metabolism. The PPAR signaling pathway plays a central role in coordinating lipid synthesis, and critical genes, such as PNPLA2, PPARA, SREBF1, and PRKAA1, were highlighted. In conclusion, grain feeding improves yak meat tenderness and fat deposition by modulating lipid metabolism at both the transcriptional and metabolic levels. This improvement, however, is balanced against a less favorable n-6/n-3 PUFA ratio. Full article

Background/Objectives: Topical steroid withdrawal syndrome is an underrecognized (and at times controversial) diagnosis, predominantly seen in individuals with a history of prolonged medium- to high-potency steroid use with sudden cessation. We aim to present topical steroid withdrawal clinical cases along with a narrative review of the literature to better characterize this understudied phenomenon. Methods: A total of 16 patients with a history of topical steroid withdrawal were enrolled in an IRB-approved clinical trial (NCT04864886). Participants underwent clinical assessments at the National Institutes of Health, including a history and physical examination, photography, genome sequencing, and comprehensive blood work. A follow-up survey assessed symptom activity and functional impact. Results: All patients reported severe itch, heat and photosensitivity, erythema, skin dryness, and pain. A total of 11 patients exhibited elevated IgE levels, 9 patients noted metallic-smelling skin, and 4 had peripheral blood eosinophilia. Symptomatic relief was observed with dupilumab, berberine, naltrexone, and various home remedies including topical ointments, vitamins, and probiotics, though effectiveness varied and often required trial and error. At follow-up, most respondents reported partial but ongoing symptoms, with several describing residual itch and intermittent interference with daily activities. Some participants continued therapeutic interventions, such as berberine, over two years after their initial evaluation. Conclusions: Our findings report improvement in patient symptoms such as itch and detail emerging management strategies that have not been discussed before. Improved recognition, physician consensus, and systemic evaluation of therapeutic options are needed to guide care and enhance quality of life for affected patients. Full article