OBJECTIVE: To explore the therapeutic effects and underlying mechanisms of Dendrobium officinale (Tiepi Shihu) extract (DOE) on insomnia. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into 6 groups (n=7 per group): normal control, model control, melatonin (MT, 40 mg/kg), and 3-dose DOE (0.25, 0.50, and 1.00 g/kg) groups. Rats were raised in a strong-light (10,000 LUX) and -noise (>80 db) environment (12 h/d) for 16 weeks to induce insomnia, and from week 10 to week 16, MT and DOE were correspondingly administered to rats. The behavior tests including sodium pentobarbital-induced sleep experiment, sucrose preference test, and autonomous activity test were used to evaluate changes in sleep and emotions of rats. The metabolic-related indicators such as blood pressure, blood viscosity, blood glucose, and uric acid in rats were measured. The pathological changes in the cornu ammonis 1 (CA1) region of rat brain were evaluated using hematoxylin and eosin staining and Nissl staining. Additionally, the sleep-related factors gamma-aminobutyric acid (GABA), glutamate (GA), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) were measured using enzyme linked immunosorbent assay. Finally, we screened potential sleep-improving receptors of DOE using polymerase chain reaction (PCR) array and validated the results with quantitative PCR and immunohistochemistry. RESULTS: DOE significantly improved rats' sleep and mood, increased the sodium pentobarbital-induced sleep time and sucrose preference index, and reduced autonomic activity times (P<0.05 or P<0.01). DOE also had a good effect on metabolic abnormalities, significantly reducing triglyceride, blood glucose, blood pressure, and blood viscosity indicators (P<0.05 or P<0.01). DOE significantly increased the GABA content in hippocampus and reduced the GA/GABA ratio and IL-6 level (P<0.05 or P<0.01). In addition, DOE improved the pathological changes such as the disorder of cell arrangement in the hippocampus and the decrease of Nissel bodies. Seven differential genes were screened by PCR array, and the GABA_A receptors (Gabra5, Gabra6, Gabrq) were selected for verification. The results showed that DOE could up-regulate their expressions (P<0.05 or P<0.01). CONCLUSION DOE demonstrated remarkable potential for improving insomnia, which may be through regulating GABA_A receptors expressions and GA/GABA ratio.
Animals ; Dendrobium/chemistry* ; Rats, Sprague-Dawley ; Male ; Sleep Initiation and Maintenance Disorders/blood* ; Plant Extracts/therapeutic use* ; Receptors, GABA-A/metabolism* ; Noise/adverse effects* ; Light/adverse effects* ; gamma-Aminobutyric Acid/metabolism* ; Sleep/drug effects* ; Rats ; Receptors, GABA/metabolism*

OBJECTIVE: To explore the anti-photoaging properties of salvianolic acid B (Sal B). METHODS: The optimal photoaging model of human immortalized keratinocytes (HaCaT cells) were constructed by expose to ultraviolet B (UVB) radiation. The cells were divided into control, model and different concentrations of Sal B groups. Cell viability was measured via cell counting kit-8. Subsequently, the levels of oxidative stress, including reactive oxygen species (ROS), hydroxyproline (Hyp), catalase (CAT), and glutathione peroxidase (GSH-Px) were detected using the relevant kits. Silent information regulator 1 (SIRT1) protein level was detected using Western blot. The binding pattern of Sal B and SIRT1 was determined via molecular docking. RESULTS: Sal B significantly increased the viability of UVB-irradiated HaCaT cells (P<0.05 or P<0.01). Sal B effectively scavenged the accumulation of ROS induced by UVB (P<0.05 or P<0.01). In addition, Sal B modulated oxidative stress by increasing the intracellular concentrations of Hyp and CAT and the activity of GSH-Px (P<0.05 or P<0.01). The Western blot results revealed a substantial increase in SIRT1 protein levels following Sal B administration (P<0.05). Moreover, Sal B exhibited good binding affinity toward SIRT1, with a docking energy of -7.5 kCal/mol. CONCLUSION Sal B could improve the repair of photodamaged cells by alleviating cellular oxidative stress and regulating the expression of SIRT1 protein.
Humans ; Sirtuin 1/metabolism* ; Ultraviolet Rays ; Oxidative Stress/radiation effects* ; Keratinocytes/metabolism* ; Molecular Docking Simulation ; Benzofurans/pharmacology* ; Skin Aging/radiation effects* ; Reactive Oxygen Species/metabolism* ; Cell Survival/radiation effects* ; HaCaT Cells ; Hydroxyproline/metabolism* ; Glutathione Peroxidase/metabolism* ; Catalase/metabolism* ; Depsides

Rosacea is a common chronic inflammatory skin disease that predominantly affects the central face. It can impair appearance and cause various discomforts, thus negatively impacting patients' physical and mental well-being as well as their quality of life. Its pathophysiological mechanisms involve multiple factors. Studies have confirmed that ultraviolet radiation plays a significant role in the pathogenesis of rosacea, affecting skin tissues, cells, DNA, and proteins, and inducing oxidative damage. Ultraviolet can lead to the occurrence and development of rosacea by up-regulating the expression of LL-37, matrix metalloproteinase, vascular endothelial growth factor, and reactive oxygen species, and influence their interactions, thereby triggering inflammatory responses, altering the dermal matrix, and promoting capillary dilation and neovascularization, which contribute to the onset and progression of rosacea. Exploring the role of ultraviolet in the pathogenesis of rosacea can provide new strategies for protection and treatment, and enhance awareness of ultraviolet protection among patients with rosacea.
Humans ; Rosacea/metabolism* ; Ultraviolet Rays/adverse effects* ; Cathelicidins ; Reactive Oxygen Species/metabolism* ; Antimicrobial Cationic Peptides/metabolism* ; Matrix Metalloproteinases/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Skin/metabolism*

OBJECTIVES: In recent years, the role of remnant cholesterol (RC) in the development and progression of cardiovascular diseases has gained increasing attention. However, evidence on the association between RC and subclinical atherosclerosis is limited. This study aims to examine the relationship between RC and atherosclerotic plaques in single and multiple vascular territories. METHODS: This retrospective cross-sectional study used baseline data from participants enrolled between October 2022 and May 2024 in the National Key Research Program "Study on the Prevention and Control System of Risk Factors for Panvascular Diseases". Color Doppler ultrasonography was performed to detect plaques in 4 vascular territories: Bilateral carotid arteries, bilateral subclavian arteries, abdominal aorta, and iliac-femoral arteries. RC was calculated as total cholesterol minus the sum of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Participants were categorized into quartiles (Q1-Q4) according to RC levels. The proportions of participants with ≥2 plaques in a single vascular territory and with plaques in ≥2 vascular territories were compared across RC quartiles. Multivariate ordinal Logistic regression was used to assess the association between RC and the number of plaques in a single vascular territory, as well as the risk of multiple vascular territory involvement. Additionally, the effects of LDL-C/RC concordance on plaque distribution were analyzed. RESULTS: A total of 3 539 participants were included, of whom 2 169 (61.29%) were male, with a age of (51.94±9.22) years. From Q1 to Q4, the proportion of participants with ≥2 plaques in a single vascular territory (bilateral carotid, subclavian, abdominal aorta, and iliac-femoral arteries), as well as those with plaques in ≥2 vascular territories, increased progressively. Compared with Q1, both Q3 and Q4 were significantly associated with higher plaque numbers in a single vascular territory (both P<0.05). When treated as a continuous variable, higher RC levels were associated with an increased risk of greater plaque numbers within a single vascular territory (all P<0.05). RC levels were also significantly associated with multiple vascular territory involvement: Compared with Q1, Q4 had a 1.015-fold higher risk [odds ratio (OR)=2.015, 95% confidence interval (CI) 1.669 to 2.433], and each 1 mmol/L increase in RC corresponded to a 0.160-fold increased risk (OR=1.160, 95% CI 1.073 to 1.271). In LDL-C/RC coordination analysis, compared with the low LDL-C/low RC group, the low LDL-C/high RC group was significantly associated with multiple vascular territory involvement (OR=1.576, 95% CI 1.220 to 2.036). CONCLUSIONS Elevated RC levels are closely associated with atherosclerotic plaques in both single and multiple vascular territories, even among individuals with normal LDL-C, suggesting that RC should be considered in clinical risk assessment and management of atherosclerosis.
Humans ; Plaque, Atherosclerotic/diagnostic imaging* ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Retrospective Studies ; Cholesterol/blood* ; Cholesterol, LDL/blood* ; Aged ; Cholesterol, HDL/blood* ; Risk Factors ; Atherosclerosis ; Ultrasonography, Doppler, Color ; Femoral Artery/diagnostic imaging*

OBJECTIVES: We present a new low-dose CT reconstruction method using sub-pixel and anisotropic diffusion. METHODS: The sub-pixel intensity values and their second-order differences were obtained using linear interpolation techniques, and the new gradient information was then embedded into an anisotropic diffusion process, which was introduced into a penalty-weighted least squares model to reduce the noise in low-dose CT projection data. The high-quality CT image was finally reconstructed using the classical filtered back-projection (FBP) algorithm from the estimated data. RESULTS: In the Shepp-Logan phantom experiments, the structural similarity (SSIM) index of the CT image reconstructed by the proposed algorithm, as compared with FBP, PWLS-Gibbs and PWLS-TV algorithms, was increased by 28.13%, 5.49%, and 0.91%, the feature similarity (FSIM) index was increased by 21.08%, 1.78%, and 1.36%, and the root mean square error (RMSE) was reduced by 69.59%, 18.96%, and 3.90%, respectively. In the digital XCAT phantom experiments, the SSIM index of the CT image reconstructed by the proposed algorithm, as compared with FBP, PWLS-Gibbs and PWLS-TV algorithms, was increased by 14.24%, 1.43% and 7.89%, the FSIM index was increased by 9.61%, 1.78% and 5.66%, and the RMSE was reduced by 26.88%, 9.41% and 18.39%, respectively. In clinical experiments, the SSIM index of the image reconstructed using the proposed algorithm was increased by 19.24%, 15.63% and 3.68%, the FSIM index was increased by 4.30%, 2.92% and 0.43%, and the RMSE was reduced by 44.60%, 36.84% and 15.22% in comparison with FBP, PWLS-Gibbs and PWLS-TV algorithms, respectively. CONCLUSIONS The proposed method can effectively reduce the noises and artifacts while maintaining the structural details in low-dose CT images.
Tomography, X-Ray Computed/methods* ; Algorithms ; Phantoms, Imaging ; Anisotropy ; Image Processing, Computer-Assisted/methods* ; Humans ; Radiation Dosage

OBJECTIVES: To investigate the protective effects of graphene heating film far-infrared (FIR) hyperthermia therapy against frostbite in mice and its impacts on microcirculation and coagulation function. METHODS: Seventy-six C57BL/6J mice were randomized into control, model, graphene-FIR, and carbon fiber-FIR groups. After 7-day FIR intervention (4 h/day), the mice were subjected to acute (4 ℃, 4 h) and intermittent (4 ℃, 4 h/day for 3 days) cold exposure and the changes in rectal temperature were monitored. In liquid nitrogen frostbite experiment, 24 ICR mice were divided into model, graphene-FIR, and carbon fiber-FIR groups, and after a 7-day FIR pretreatment (4 h/day), the liquid nitrogen frostbite models were established and apparent scores of the wounds were assessed on days 3 and 6 after modeling. In carrageenan-induced thrombosis experiment, 40 ICR mice were allocated to control, model, graphene-FIR, carbon fiber-FIR, and prazosin groups to test the effect of a 7-day FIR intervention on thrombosis induced by intraperitoneal carrageenan injection (2.5 mg/kg) by measuring thrombus length, blood perfusion, and serum biomarkers (6-keto-PGF1α, TXB2, t-PA, IL-6, IL-1β, TNF‑α) 24 h after the injection. RESULTS: The mice in graphene-FIR group showed significantly elevated rectal temperature in cold exposure tests. In mice with liquid nitrogen-induced frostbite, graphene-FIR treatment significantly reduced the wound scores and reduced frostbite area, producing better effects than carbon fiber. In mice with carrageenan-induced thrombosis, graphene-FIR treatment significantly decreased tail thrombosis length and thrombosis area, increased blood perfusion, lowered serum levels of TXB2, TNF-α and IL-6, and increased the levels of 6-keto-PGF1α and t-PA. CONCLUSIONS Graphene heating film FIR therapy can alleviate frostbite injury in mice by improving microcirculation, suppressing thrombosis and inflammatory responses, and reducing coagulation dysfunction.
Animals ; Frostbite/therapy* ; Graphite ; Mice, Inbred C57BL ; Mice ; Infrared Rays ; Mice, Inbred ICR ; Hyperthermia, Induced/methods* ; Male ; Microcirculation

Previous studies have found associations between color discrimination deficits and cognitive impairments besides aging. However, investigations into the microstructural pathology of brain white matter (WM) associated with these deficits remain limited. This study aimed to examine the microstructural characteristics of WM in the non-demented population with abnormal color discrimination, utilizing Neurite Orientation Dispersion and Density Imaging (NODDI), and to explore their correlations with cognitive functions and cognition-related plasma biomarkers. The tract-based spatial statistic analysis revealed significant differences in specific brain regions between the abnormal color discrimination group and the healthy controls, characterized by increased isotropic volume fraction and decreased neurite density index and orientation dispersion index. Further analysis of region-of-interest parameters revealed that the isotropic volume fraction in the bilateral anterior thalamic radiation, superior longitudinal fasciculus, cingulum, and forceps minor was significantly correlated with poorer performance on neuropsychological assessments and to varying degrees various cognition-related plasma biomarkers. These findings provide neuroimaging evidence that WM microstructural abnormalities in non-demented individuals with abnormal color discrimination are associated with cognitive dysfunction, potentially serving as early markers for cognitive decline.
Humans ; White Matter/pathology* ; Male ; Female ; Cognitive Dysfunction/physiopathology* ; Middle Aged ; Aged ; Color Perception/physiology* ; Brain/pathology* ; Neuropsychological Tests ; Diffusion Tensor Imaging

The advancement of tissue clearing technology has significantly propelled neuroscience research. Nevertheless, the fluorescent proteins used in traditional transgenic mouse strains were not specifically optimized for tissue clearing procedures, resulting in a substantial decrease in fluorescent intensity after clearing. In this study, we developed the Ci1 reporter mouse strain (where Ci stands for the Chinese Institute for Brain Research, CIBR) based on the bright red fluorescent protein mScarlet. The Ci1 reporter exhibits no fluorescence leakage in various organs or tissue types and can be readily crossed with multiple tissue-specific Cre lines. Compared to the Ai14 mouse strain, the Ci1 reporter strain demonstrates lower non-specific leakage, stronger fluorescence intensity in different tissues, and better preservation of fluorescence following tissue clearing treatment. The creation of the Ci1 reporter provides a more effective tool for both neuroscience and other biomedical research applications.
Animals ; Luminescent Proteins/metabolism* ; Mice, Transgenic ; Mice ; Red Fluorescent Protein ; Brain/metabolism* ; Genes, Reporter ; Fluorescence

Our research reveals the critical role of the suprachiasmatic nucleus (SCN) vasoactive intestinal peptide (VIP) neurons in mediating light-induced transient forgetting. Acute exposure to bright light selectively impairs trace fear memory by activating VIP neurons in the SCN, as demonstrated by increased c-Fos expression and Ca²⁺ recording. This effect can be replicated and reversed through optogenetic and chemogenetic manipulations of SCN VIP neurons. Furthermore, we identify the SCN → PVT (paraventricular nucleus of the thalamus) VIP neuronal circuitry as essential in this process. These findings establish a novel role for SCN VIP neurons in modulating memory accessibility in response to environmental light cues, extending their known function beyond circadian regulation and revealing a mechanism for transient forgetting.
Animals ; Vasoactive Intestinal Peptide/metabolism* ; Male ; Mice ; Neurons/metabolism* ; Suprachiasmatic Nucleus/physiology* ; Light ; Mice, Inbred C57BL ; Memory/physiology* ; Fear/physiology* ; Suprachiasmatic Nucleus Neurons/metabolism* ; Optogenetics ; Proto-Oncogene Proteins c-fos/metabolism*

Oroxylin A (OA), a natural compound extracted from Scutellaria baicalensis, demonstrates preventive potential against ultraviolet B (UVB)-induced non-melanoma skin cancer (NMSC), the most prevalent cancer worldwide with increasing incidence. Utilizing SKH-1 hairless mice exposed to UVB, this study showed that OA delayed NMSC onset and alleviated acute skin damage. Mechanistic investigations revealed its dual action: inhibiting inflammation and enhancing nucleotide excision repair (NER) by stabilizing XPA, a crucial deoxyribonucleic acid (DNA) repair protein. This stabilization occurred through OA's interaction with glucose-regulated protein 94 (GRP94), which disrupted murine double minute 2 (MDM2)-mediated XPA ubiquitination and proteasomal degradation. By maintaining XPA levels, OA expedited photoproduct clearance and diminished genomic instability, ultimately impeding NMSC development. These findings suggest OA as a promising chemopreventive agent targeting the GRP94/MDM2-XPA axis to counteract UVB-induced carcinogenesis.
Animals ; Ultraviolet Rays/adverse effects* ; Skin Neoplasms/prevention & control* ; Flavonoids/pharmacology* ; Mice ; Xeroderma Pigmentosum Group A Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-mdm2/genetics* ; DNA Repair/drug effects* ; Scutellaria baicalensis/chemistry* ; Mice, Hairless ; Skin/radiation effects*