Background: Sex-based differences often influence the therapeutic efficacy and safety of medications. Semen Cuscutae is a traditional tonic botanical drug with sex-specific characteristics, traditionally indicated for conditions such as impotence (exclusive to males) and restless fetus (exclusive to pregnant females). However, most existing studies have focused on a single sex. Objective: To evaluate the sex-specific biological effects of Semen Cuscutae in rats and explore its molecular mechanisms, with the aim of uncovering its pharmacological characteristics through a multiomics approach. Methods: A traditional aqueous extract of Semen Cuscutae (SCA) was used as the experimental material. Forty adult Sprague-Dawley rats (equal numbers of males and females) were randomly divided into 4 groups: male control, male SCA treatment (240 mg/kg), female control, and female SCA treatment (240 mg/kg), with 10 rats in each group. The biological effects were comprehensively evaluated using a combination of open field test, biochemical analyses, proteomics, and gut microbiota profiling. Results: As a tonic botanical drug, SCA appeared to directly affect the mental and behavioral state of rats. It significantly altered the time spent by rats in the center area during the open field test, showing a sex-dependent reversal of behaviors. Proteomic analysis of brain tissue identified 624 differentially expressed proteins across the groups, with 10 key differentially expressed proteins related to sex differences, including fibroblast growth factor receptor 3, transcription elongation factor A protein-like 1, 40S ribosomal protein S25, neural cell adhesion molecule, and anion exchange protein 2 (SLC4A2). Enrichment analysis revealed that in male rats, SCA upregulated proteins involved in biological processes such as ribosome function and energy derivation, supporting protein synthesis and enhancing energy supply, showing an overall gain effect. In contrast, in female rats, SCA downregulated proteins associated with processes such as positive regulation of target of rapamycin (TOR) signaling and vesicle transport, suggesting suppression of neuronal signaling and material transport, indicative of a shift toward a more restrained physiological state. Furthermore, SCA reduced gut microbiota diversity in female rats but increased it in males, including the abundance of Akkermansia, which may serve as a crucial mediator. Conclusion: Overall, the biological effects of SCA differ significantly between male and female rats, with evidence suggesting greater health benefits in males. These findings help elucidate the scientific basis of its traditional applications and provide guidance for the precise application of SCA as a functional health food.

ObjectiveThe functional model of six major components of Astragali Radix-Angelicae Sinensis Radix combination against the proliferation of vascular smooth muscle cells （VSMCs） was constructed by uniform design， the relationship between the compatibility of these six main components and the inhibition of VSMCs proliferation was analyzed， and the effect of the compatibility of these main components of Astragali Radix-Angelicae Sinensis Radix on the proliferation of VSMCs as well as the feasibility of uniform design test in the study of multi-component compatibility of Chinese medicines were discussed. MethodCell proliferation and toxicity assay kit （CCK-8） method was used to determine the inhibitory effect of the six components of Astragali Radix-Angelicae Sinensis Radix on platelet derived growth factor-BB （PDGF-BB）-induced VSMCs proliferation in rats and the half inhibitory concentration （IC₅₀） of each component were obtained. Six chemical components of Astragali Radix-Angelicae Sinensis Radix （formononetin， astragaloside Ⅰ， astragaloside Ⅳ， calycosin， ferulic acid and calycosin-7-O-β-D-glucoside） were taken as the independent variables X₁， X₂， X₃， X₄， X₅， X₆， respectively， and the cell proliferation inhibition rate as the dependent variable Y. U24*（24⁹） uniform design table and mathematical models （including linear and quadratic polynomial） were selected， the stepwise regression method was used to screen the variables， and the better equations were obtained in theory. The actually better relationship equations were screened by setting the different dose compatibility of these six components for verification tests. According to the purpose of the experiment， the selected regression equation was processed by data centralization， so as to compare the regression coefficients of the data centralization equation and analyze the correlation between components and efficacy. ResultThe six components of Astragali Radix-Angelicae Sinensis Radix could inhibit abnormal proliferation of VSMCs in a dose-dependent manner. IC₅₀ values of formononetin， astragaloside Ⅰ， astragaloside Ⅳ， calycosin， ferulic acid and calycosin-7-O-β-D-glucoside were 123.453， 113.184， 81.655， 141.159， 101.187， 151.016 mg·L^-1， respectively. Two superior models were selected by experimental verification， including equation 1 of Y₁=73.137 897-0.207 888X₁+0.000 508X₂²+0.000 347X₁X₆ and equation 2 of Y₂=70.038 433-0.236 665X₁+0.000 577X₂²+0.000 260X₁X₄+0.000 415X₁X₆+0.000 370X₃X₅. After data centralization， equation 2 was adjusted to Y=-1.480 260-0.146 281X₁+0.000 673X₂²+0.000 314X₁X₄+0.000 456X₁X₆+0.000 737X₃X₅， the regression coefficients showed that the astragaloside Ⅰ had a positive effect on the inhibition rate of cell proliferation， formononetin-calycosin， formononetin-calycosin-7-O-β-D-glucoside and astragaloside Ⅳ-ferulic acid had an interaction effect on the inhibition rate of cell proliferation， and the synergistic effect of astragaloside Ⅳ and ferulic acid was higher than other interaction items. ConclusionThe combination of six main components of Astragali Radix-Angelicae Sinensis Radix can inhibit the abnormal proliferation of VSMCs， and it is demonstrated that the uniform test design can be used to predict the correlation between the chemical composition of Chinese medicines with their pharmacological effects， which can provide an experimental basis for the rational use of uniform design and regression analysis to construct mathematical models to study the compatibility relationship of Chinese medicines.

OBJECTIVE To study the effect of epipolythiodioxopiperazine compound C87 on tumor cell proliferation and explore the potential mechanisms. METHODS Tumor cells were exposed to C87 0.05-1 μmol.L-1 for 24, 48 and 72 h, cell viability was determined by sulforhodamine B (SRB) assay and the half growth inhibition (Gl50 ) was calculated. After treatment with C87 0.1-2.5 μmol.L-1 for 6 h, or C87 2.5 μmol.L-1 for 0-6 h, the generation of reactive oxygen species (ROS) was measured using the compound 2′,7′-dichlorofluoresceindiacetate and flow cytometry analysis. After treatment with C87 2.5 μmol.L-1 , either alone or with antioxidant N-acetylcysteine (NAC), for 6 h, the generation of ROS was measured by flow cytometry analysis. Tumor cells were exposed to C87 0.05-1 μmol.L-1 , either alone or with NAC, for 24 and 48 h, while cell viability was determined by SRB assay. RESULTS The cell viability was significantly reduced following exposure to C87 0.05-1 μmol.L-1 for 24, 48 and 72 h in a concentration-dependent manner in A549, HCT116, HeLa and SMMC7721 cells(P<0.05). At 72 h, the value of r2 was 0.946, 0.989, 0.973 and 0.984(P<0.05), respectively. The cell viability was significantly reduced following exposure to C87 1 μmol.L-1 for 24 - 72 h in a time-dependent manner in A549, HCT116, HeLa and SMMC7721 cells(P<0.05). The value of r2 was 0.983, 0.956, 0.951 and 0.873(P<0.05), respectively. The generation of ROS was increased after exposure to C87 0.25-2.5 μmol.L-1 in a concentration-dependent manner in HCT116 and HeLa cells for 6 h (r2 = 0.760, P = 0.045: r2 = 0.987, P=0.001), and after exposure to C87 2.5 μmol.L-1 in a time-dependent manner in HCT116 and HeLa cells for 0.5-6 h (r2 = 0.886, P = 0.017: r2 = 0.994, P = 0.000).The C87-induced ROS generation could be blocked by NAC in HCT116 and HeLa cells(P<0.05). The C87 induced cell death could be blocked by NAC 5 and 10 mmol.L-1 , and the Gl50 value was 1.446 and 1.134 μmol.L-1 for 24 h (the Gl50 value of C87 group was 0.513 μmol.L-1 ), and 0.882 and 1.166 μmol.L-1 for 48 h (the Gl50 value of C87 group was 0.333 μmol.L-1 ). CONCLUSION The novel epipolythiodioxopiperazine derivative C87 exerts potent antitumor activity in vitro, possibly via triggering ROS production.

Objective To investigate the incidence of autoimmune and nonautoimmune thyroid diseases in patients with breast cancer.Methods Clinical and ultrasound evaluation of thyroid gland,detection of serum thyroid hormone and related antibodies,and fine-needle aspiration of thyroid gland were performed in 100 breast cancer patients and 100 control individuals during the period from 2004 to 2008.Results The mean values of anti-thyroid peroxidase antibodies were significantly higher in breast cancer patients than that in control individuals [(104.56±21.54) U/ml vs (22.16±4.65) U/ml,(P=0.030)].The incidence rates of autoimmune and nonautoimmune thyroid diseases were higher in breast cancer patients than that in control individuals[38 ％ (38/100) vs 17 ％ (17/100),P=0.0009,26 ％ (26/100) vs 9 ％ (9/100),P =0.0016,respectively].Conclusion The results indicate an increased incidence of autoimmune and nonautoimmune thyroid diseases in breast cancer patients.