Alzheimer’s disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory loss. As the incidence of AD continues to rise annually, researchers have shown keen interest in the active components found in natural plants and their neuroprotective effects against AD. Quercetin, a flavonol widely present in fruits and vegetables, has multiple biological effects including anticancer, anti-inflammatory, and antioxidant. Oxidative stress plays a central role in the pathogenesis of AD, and the antioxidant properties of quercetin are essential for its neuroprotective function. Quercetin can modulate multiple signaling pathways related to AD, such as Nrf2-ARE, JNK, p38 MAPK, PON2, PI3K/Akt, and PKC, all of which are closely related to oxidative stress. Furthermore, quercetin is capable of inhibiting the aggregation of β‑amyloid protein (Aβ) and the phosphorylation of tau protein, as well as the activity of β‑secretase 1 and acetylcholinesterase, thus slowing down the progression of the disease.The review also provides insights into the pharmacokinetic properties of quercetin, including its absorption, metabolism, and excretion, as well as its bioavailability challenges and clinical applications. To improve the bioavailability and enhance the targeting of quercetin, the potential of quercetin nanomedicine delivery systems in the treatment of AD is also discussed. In summary, the multifaceted mechanisms of quercetin against AD provide a new perspective for drug development. However, translating these findings into clinical practice requires overcoming current limitations and ongoing research. In this way, its therapeutic potential in the treatment of AD can be fully utilized.

BACKGROUND:Exercises can reduce blood lipids and slow down the development of atherosclerosis.Atherosclerosis begins with mitochondrial dysfunction,and prohibitin 2 is involved in mitophagy by endurance training. OBJECTIVE:To explore the role of endurance training in the intervention of prohibitin 2 protein in the mitophagy autophagy pathway in atherosclerosis. METHODS:A total of 40 Wistar rats were randomly divided into control group,exercise group,atherosclerosis group and atherosclerosis combined with exercise group,with 10 rats in each group.A rat model of atherosclerosis was constructed by combining a high-fat diet(9 weeks)with vitamin D injections(weeks 1,3,and 6)in the latter two groups,while the two exercise groups were subjected to progressing intensity endurance training for 9 weeks.After the intervention,lipid and pathological detections were conducted to observe the modeling and interventional effects.Mitochondrial membrane potential and mitophagy proteins were detected by microplate reader and western blot.Immunofluorescence staining was used to observe the co-localization of mitophagy proteins in aortic tissue. RESULTS AND CONCLUSION:Lipid and pathological sections showed that compared with the atherosclerosis group,the serum low-density lipoprotein cholesterol and total cholesterol levels and aortic lipid deposition area were significantly reduced in the atherosclerosis combined with exercise group(P<0.001).The results of mitochondrial membrane potential showed that the significant decrease in mitochondrial membrane potential of the aorta in the atherosclerosis combined with exercise group was reversed(P<0.01).The results of western blot assay showed that compared with the control group,the mitochondrial protein expression of prohibitin 2,LC3Ⅱ/Ⅰ,PINK1 and Parkin was significantly increased(P<0.05),and the protein expression of PARL and PGAM5 decreased(P<0.05).Compared with the atherosclerosis group,the protein expression of PINK1 and Parkin in the mitchondria of rats in the atherosclerosis combined with exercise group was significantly decreased(P<0.05),and the protein expressions of prohibitin 2,LC3Ⅱ/Ⅰ,PARL and PGAM5 were significantly increased(P<0.05).Immunofluorescence results showed that compared with the control group,the co-localization of LC3 and PINK1 with TOMM20 was significantly increased in the atherosclerosis group(P<0.05),while compared with the atherosclerosis group,the co-localization of LC3 and PINK1 with TOMM20 was significantly increased in the atherosclerosis combined with exercise group(P<0.05).Co-localization of LC3 and PARL with prohibitin 2 was significantly increased in the atherosclerosis group compared with the control group(P<0.01),co-localization of LC3 with prohibitin 2 was significantly increased in the atherosclerosis combined with exercise group compared with the atherosclerosis group(P<0.01),and co-localization of PARL protein with prohibitin 2 was significantly decreased in the atherosclerosis combined with exercise group compared with the atherosclerosis group(P<0.01).To conclude,endurance training can induce the expression of prohibitin 2 in the inner mitochondrial membrane and promote the binding of prohibitin 2 to the mitophagy junction protein to complete mitophagy,restore mitochondrial function,and slow down the occurrence of atherosclerosis.

ObjectiveTo investigate the effects of Ningxin Shugan decoction combined with an antagonist fixation regimen on in vitro fertilization and embryo transfer （IVF-ET） outcomes and serum kisspeptin expression in infertility patients with polycystic ovary syndrome. MethodsA total of 96 infertile patients with polycystic ovary syndrome treated in Yancheng No.1 People's Hospital and Yancheng Affiliated Hospital of Nanjing University of Chinese Medicine were enrolled in this study and randomized into control and observation groups （n=48）. The control group was treated with an antagonist fixation regimen， and the observation group was treated with Ningxin Shugan decoction on the basis of the treatment in the control group. The clinical efficacy was compared between the two groups. The total score and single scores of TCM symptoms， ovulation promotion status， and serum levels of reproductive hormones， miR-335-5p， miR-141-3p， and kisspeptin were determined before and after treatment. The IVF-ET outcome indicators and treatment safety were evaluated. Pearson test was conducted to analyze the correlations of serum levels of follicle-stimulating hormone （FSH）， kisspeptin， miR-335-5p， and miR-141-3p with IVF-ET outcomes. ResultsThe total response rate in the observation group was 90.91%， which was higher than that （70.45%） in the control group （P<0.05）. The total score and single scores of TCM symptoms and the testosterone， luteinizing hormone （LH）， and LH/FSH levels declined after treatment （P<0.05）， and they were lower in the observation group than in the control group （P<0.05）. After treatment， the serum levels of FSH， kisspeptin， miR-335-5p， and miR-141-3p rose in both groups， being higher in the observation group than in the control group （P<0.05）. The observation group showed higher ovulation number， number of MⅡ oocytes， embryo implantation rate， clinical pregnancy rate， and live birth rate than the control group （P<0.05， P<0.01）. Serum levels of FSH， kisspeptin， miR-335-5p， and miR-141-3p were positively correlated with embryo implantation rate， clinical pregnancy rate， and live birth rate （P<0.01）. ConclusionNingxin Shugan decoction combined with the antagonist fixation regimen can improve the IVF-ET outcome， promote the serum kisspeptin expression， and increase the ovulation rate and pregnancy rate in infertility patients with polycystic ovary syndrome.

This paper discussed the nature of ulcerative colitis， that is deficiency of the root and excess of the branch， from the theory of sweat pore， and to explore the theoretical basis and experience of treating this disease with retention enema of traditional Chinese medicine （TCM）. The main location of this disease is in the intestine. As a part of sweat pore， the intestinal sweat pore serves as the gateway for the ascending， descending， exiting and entering of qi movement in the zang fu （脏腑） organs， meridians and collaterals， as well as the channel for the transportation of qi， blood and body fluids. The constraint and closure of the intestinal sweat pore are the main pathological basis of ulcerative colitis. According to the manifestations of colonoscopy， and the different etiological factors and pathogenesis that lead to the constraint and closure of sweat pore， there should be different treatment focuses such as expelling wind to open sweat pore， clearing fire to open sweat pore， promoting blood circulation to open sweat pore， for which wind-dispersing herbs， heat-clearing herbs， and blood-activating herbs are used accordingly. The method of retention enema can directly induce Chinese medicinal herbs to the affected part， so as to diffuse and unblock the sweat pore， regulate qi and blood， and thus restore the normal function of the intestinal sweat pore.

Objective: To analyze the status and trends of the disease burden of periodontal disease among women of reproductive age (15-49 years) in China from 1990 to 2021, and to provide a reference for the development of periodontal disease prevention and control strategies for women of reproductive age. Methods: Using the global burden of disease (GBD) data from 1990 to 2021, this study investigated the periodontal disease burden among women of reproductive age, including prevalence, incidence, disability-adjusted life years (DALYs), DALY rates, and their corresponding standardized indicators. Joinpoint 5.2.0.0 software was used for time trend analysis of DALYs, age-specific DALY rates, and annual average percentage change (AAPC) values. A log-linear regression model was used to test trends for DALYs and DALY rates. Results: Compared with 1990, the prevalence and incidence of periodontal disease among Chinese women in 2021 increased by 45.67% (per 100,000 people) and 29.29% (per 100,000 people), respectively. The distribution of periodontal disease among women (15-49 years) showed a continuous and rapid upward trend, with the growth rate increasing rapidly with age. The number of cases increased the fastest in the 45-49 age group, and the prevalence increased the fastest in the 35-44 age group. The incidence of periodontal disease continued to rise with age, with the fastest increase in the 35-44 age group among women of reproductive age. The Joinpoint regression model results showed that periodontal disease led to an expanding trend in the disease burden among women of reproductive age in China, with an AAPC of DALYs = 1.20% and an AAPC of DALY rate = 1.25% (P<0.001). Conclusion The periodontal disease burden among Chinese women aged 15-49 years showed a gradually increasing trend from 1990 to 2021.

Five compounds were isolated and purified from the water extract of Elaeagnus oxycarpa Schlechtend leaf by multi-dimensional reversed-phase preparative liquid chromatographic system based on the separation and enrichment model. Their structures were identified by spectral analysis such as NMR, MS, UV, IR and by comparison with literature information as 2,4(1H,3H)-pyrimidinedione (1), elaeagnussugarester B (2), elaeagnussugarester A (3), elaeagnussugarester C (4), gallic acid (5). Compounds 2-4 are new compounds, compound 1 was isolated from Elaeagnus oxycarpa Schlechtend for the first time. The antioxidant and anti-tyrosinase activities of these compounds were evaluated by using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical method, the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical method, the potassium ferricyanide reduction method and the colorimetric method with L-tyrosine as substrate. The results showed that compounds 2-5 have good antioxidant activities and inhibitory effect on tyrosinase. Compound 4 exhibited the most strong antioxidant activities, with IC₅₀ = 3.59 ± 0.06 μmol·L^-1 for DPPH free radical scavenging ability, IC₅₀ = 10.04 ± 0.20 μmol·L^-1 for ABTS free radical scavenging ability, and total reduction capacity of compound 4 was better than vitamin C respectively. Compound 3 possessed better inhibitory effect on tyrosinase with IC₅₀ = 0.25 ± 0.06 mmol·L^-1.

This study aimed to investigate the therapeutic effect of Yindan Pinggan capsules (YDPG) on intrahepatic cholestasis (IHC) through animal experiments, while utilizing network pharmacology and molecular docking techniques to explore its potential mechanisms. Initially, the therapeutic effect of YDPG on an α-naphthylisothiocyanate (ANIT)-induced IHC mouse model was assessed through liver function tests, routine blood tests, and liver pathology analysis. Subsequently, network pharmacology tools were employed to predict the active components, core targets, and signaling pathways of YDPG. Molecular docking technology was employed to verify the binding activity of key active components of YDPG with core targets, followed by protein immunoblotting to validate the key targets. Results showed that YDPG significantly improved liver function abnormalities and hepatocyte damage in IHC mice. Network pharmacology analysis revealed that 94 active components in YDPG were associated with 396 targets for the treatment of IHC, and were significantly enriched in pathways such as the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway, lipid metabolism, and bile secretion. Molecular docking results showed good binding activity between key active components of YDPG and core targets of the PI3K-AKT signaling pathway. Further protein immunoblotting confirmed that YDPG could reduce the phosphorylation levels of PI3K and AKT proteins, core targets of the PI3K-AKT pathway in liver tissue. These findings suggest that YDPG may alleviate biological processes such as oxidative stress and inflammatory responses by regulating the PI3K-AKT signaling pathway, thereby improving liver damage in IHC mice and exerting a therapeutic effect on IHC. This experiment has been approved by the Animal Experiment Ethics Committee of Jinan University (ethical approval number: IACUC-20241011-09).

ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.

Background Protein tyrosine phosphatase non-receptor type II (PTPN2) is essential for the regulation of inflammation and immunity, but the specific mechanism of action of Ptpn2 in silicosis is unknown. Objective To investigate the regulatory role of overexpression of Ptpn2 in SiO₂-mediated inflammatory response in alveolar type II epithelial cells based on transcriptome sequencing. Methods This study was an in vitro study. A negative control group (vector transferred) and an overexpression of Ptpn2 group of mouse lung epithelial cell line MLE-12 cells were firstly constructed. Transcriptome sequencing was performed to detect differentially expressed genes (DEGs), differentially expressed mRNAs, and differentially expressed ncRNAs in the two groups of MLE-12 cells, and then the DEGs were analyzed by the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Constructed MLE-12 cells and A549 cells were stimulated using SiO₂ suspension, and divided into a negative control group (vector transferred), an overexpression of Ptpn2 group, a negative control + SiO₂ group, and an overexpression of Ptpn2 + SiO₂ group, respectively. Protein expressions of tumor necrosis factor-α (TNF-α) and interleukin (IL)-17A, IL-2, IL-1β were detected by Western blot. Positive TNF-α expression was detected by immunofluorescence staining. Results The results of Western blot showed that the protein expression level of PTPN2 was up-regulated in the overexpressed Ptpn2 group compared with the negative control group (P < 0.05). The volcano plot and clustering heat map showed that there were 1122 DEGs, 3681 differentially expressed mRNAs, and 474 differentially expressed ncRNAs in the overexpressed Ptpn2 group compared with the negative control group. The results of GO enrichment showed that, in terms of the biological process, the DEGs were mainly related to the regulation of metal ion transport, extracellular matrix organization, and extracellular structural organization; in terms of cellular composition, the DEGs were mainly related to collagen-containing extracellular matrix, receptor complexes, and basement membranes; in terms of molecular function, the DEGs were mainly related to the extracellular matrix structural constituents, glycosaminoglycan binding, and semaphorin receptor binding. The results of KEGG enrichment showed that the DEGs were closely related to cytokin-cytokine receptor interaction, IL-17 signaling pathway, TNF signaling pathway, and chemokine signaling pathway. In MLE-12 and A549 cells, the results of Western blot showed that the protein expression levels of TNF-α , IL-17A, IL-2, and IL-1β were up-regulated in the negative control + SiO₂ group compared with the negative control group (P < 0.05), and the protein expression levels of TNF-α, IL-17A, IL-2, and IL-1β were down-regulated in the overexpression of Ptpn2 + SiO₂ group compared with the negative control + SiO₂ group (P < 0.05). The immunofluorescence staining showed that the expression of TNF-α was increased in the negative control + SiO₂ group compared with the negative control group, and decreased in the overexpression of Ptpn2 + SiO₂ group compared with the negative control + SiO₂ group. Conclusion Overexpression of Ptpn2 inhibits SiO₂-mediated inflammatory response in MLE-12 cells and A549 cells.