Chinese Journal of Integrative Medicine最新文献

Objective: To verify effect of baicalein on recurrent pregnancy loss (RPL) and explore its mechanism via inhibition of ferroptosis.

Methods: In vivo, CBA/J (n=60) mated DBA/2 (n=50) mice were established as RPL group, while CBA/J mated BALB/c (n=10) mice were regarded as control group. Baicalein (10 and 40 mg/kg), ferroptosis inhibitor (ferrostatin-1, 5 mg/kg) and iron chelator (deferoxamine, 1 mg/kg) were administered in the RPL mice model (n=10 per group) from embryonic day 0.5-12.5 (E0.5-E12.5). Pregnancy outcomes and ferroptosis related markers were detected. Lipid peroxidation was assessed by malondialdehyde (MDA) and antioxidant system was determined by glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity. The Fe²⁺ concentration was tested to analyze iron accumulation and Western blotting was performed to detect key protein expressions. In vitro, different concentrations of baicalein (0.1, 0.2, and 0.4 µmol/L) were supplemented under the exposure of erastin in HTR-8/SVneo cells. Moreover, RSL3 and si-RNA were used to suppress the expression of glutathione peroxidase 4 (GPx4) or nuclear factor erythroid 2-related factor 2 (Nrf2), respectively, in HTR-8/SVneo cells. Cell viability, cytotoxicity, ferroptosis related markers, protein expressions of Nrf2 and GPX4 were detected in HTR-8/SVneo cells to determine the signaling pathway of baicalein against ferroptosis.

Results: Baicalein significantly attenuated fetal loss (P<0.01) and placental damage in RPL mice. Besides, baicalein reduced placental ferroptosis which manifested decreased MDA, iron content, Acyl-CoA synthetase long-chain family protein expression and enhanced GSH and GPx levels (P<0.01) as well as increased protein expressions that were resistant to ferroptosis (GPx4, SLC7A11 and Nrf2, P<0.01 or P<0.05). In vitro, different concentrations of baicalein restored a ferroptosis inducer-erastin induced HTR-8/SVneo cells damage and lipid peroxidation, but GPx4 inhibition diminished the protective effect of baicalein (P<0.01). Additionally, Nrf2 silencing notably decreased GPx4 expression (P<0.01) and abolished baicalein-mediated anti-ferroptosis effect in HTR-8/SVneo cells.

Conclusion: Baicalein has a protective effect on RPL via inhibiting ferroptosis through Nrf2/GPx4 signaling axis.

Objective: To investigate the therapeutic effects and mechanisms of curcumin (Cur) in adenomyosis (AM).

Methods: A mouse uterine AM model was established by exposing ICR neonatal mice to tamoxifen (TAM). Female neonatal mice (day 1, n=24) were numbered and randomly divided into control, model (TAM 1 mg/kg per day, day 2 to 5), low- and high-doses Cur groups (TAM 1 mg/kg per day, day 2 to 5; Cur 50 and 200 mg/kg per day, respectively, week 13 to 15), by a random number table, with 6 mice in each group. The effect of Cur was assessed by a hot-plate test on mice and uterine sections for hematoxylin and eosin (HE), Masson staining, and immunohistochemistry staining of E-cadherin, N-cadherin, matrix metalloproteinases (MMP) 9 and MMP 11. Ishikawa (IK) cell phenotypic transformation was induced by transforming growth factor beta 1 (TGF-β1), and the mRNA and protein expressions of E-cadherin, N-cadherin, MMP 9, MMP 11 and p-Smad3/Smad3 were detected by quantitative real-time PCR and Western blot after Cur treatment.

Results: In vivo study results showed that Cur significantly improved pain tolerance (P<0.01). The degrees of lesion fibrosis and invasion of ectopic glands in model mice were significantly higher than those in control mice, and the degrees were significantly reduced after high-dose Cur treatment (P<0.01). High-dose Cur reversed the decrease of E-cadherin and the increase of the levels of N-cadherin, MMP 9 and MMP11 by inhibiting the production of TGF-β1 in the uterine tissue (P<0.01). In vitro study, Cur increased the protein expression of E-cadherin and reduced the protein expressions of N-cadherin, MMP 9 and MMP 11 (P<0.01). Cur effectively inhibited the phosphorylation of p-Smad3/Smad3 in IK cells induced by TGF-β1 (P<0.01).

Conclusion: Cur effectively alleviates AM and inhibits fibroblast differentiation and epithelial-mesenchymal transition by TGF-β1/Smad3 pathway, which provides a new approach for treating AM by non-hormonal drugs.

Objective: To evaluate the effects and safety of auricular acupressure combined with periocular thumbtack needle (AATN) therapy for premyopia children.

Methods: This multi-center, randomized, controlled trial was conducted in 8 Chinese hospitals, and 298 premyopic children aged 6 to 10 years were recruited between October 2020 and February 2022. Eligible participants were randomly assigned to the treatment group or the control group via a simple randomization method. All the participants in both groups were provided with standard intensive eye health instruction through phone calls, WeChat or hospital visits once a week, and the children in the treatment group received AATN therapy additionally. Following 12-week treatment, participants were followed up at 3-month intervals, with the entire study extending over a 9-month duration from baseline to the final assessment. The primary outcome was the mean change in spherical equivalent (SE) from baseline to 36 weeks. The secondary outcomes included the rate of children with stable myopia (MSR), uncorrected visual acuity (UCVA), axial length (AL), corneal curvature (CC), accommodative amplitude (AMP) and intraocular pressure (IOP) at baseline, 6,12, 24 and 36 weeks. Safety assessment included analysis of treatment-related adverse events (AEs), such as allergic reactions and skin damage.

Results: Totally, 298 children with premyopia were included, 151 in the treatment group and 147 in the control group. At the 36th week, the SE was -0.81±0.55 D in the control group and -0.65±0.44 D in the treatment group (P=0.002). The treatment group demonstrated superior SE control efficacy compared with the control group, with differences of -0.29±0.37 D and -0.49±0.44 D, respectively (P<0.01). The children in the treatment group achieved a MSR of 57.78% with more favorable outcome than 37.10% in the control group (P<0.01). The adjusted mean change in AMP from baseline to 9th month was 8.85±4.02 in the control group and 9.85±3.41 in the treatment group (P=0.018). AL increased by a mean of 0.35±0.28 mm in the control group and 0.20±0.42 mm in the treatment group (P=0.004). No significant differences in UCVA or CC were found between the two groups (P>0.05) and no AEs were reported.

Conclusion: AATN therapy was effective for controlling the onset of myopia and SE, enhancing ocular accommodation, and mitigating AL. (Registration No. ChiCTR2000039299).

Objective: To assess the effectiveness and safety of Biqi Capsules in the treatment of rheumatoid arthritis (RA).

Methods: This multicenter, prospective cohort study was conducted across more than 100 centers in China. Data on RA patients were collected from the CERTAIN database between January 2019 and March 2024. Patients were categorized into an exposed group and a control group. The control group was treated with conventional Western medicine, and the exposed group was combined with Biqi Capsules (0.3 g/capsule, 4 capsules per dose, orally, 2-3 times/d) on the basis of conventional treatment. Propensity score matching (PSM) was applied to balance baseline characteristics. The main outcomes was the Disease Activity Score-28 (DAS28-ESR), and secondary outcomes included Health Assessment Questionnaire (HAQ), Visual Analogue Scale (VAS) for pain, tender joint count (TJC), swollen joint count (SJC), Patient Global Assessment (PGA), and Evaluator Global Assessment (EGA) scores, as well as erythrocyte sedimentation rate (ESR), and other laboratory test results as safety indicators.

Results: A total of 2,267 patient records were analyzed, with 711 in the exposed group and 1,556 in the control group. After PSM, 710 patients were included in each group, with comparable baseline demographic characteristics (P>0.05). Following matching, pre-treatment HAQ and TJC were similar between groups (P>0.05), while significant differences were observed in DAS28-ESR, EGA, PGA, VAS, SJC, TJC, and ESR (P<0.01). Post-treatment analysis showed that all indices improved significantly in both groups (P<0.01). Furthermore, post-treatment levels of EGA, PGA, VAS, SJC, and TJC were statistically significant between the two groups (P<0.01). The reduction in DAS28-ESR was significantly greater in the exposed group than in the control group (P<0.01). Statistically greater improvements were also found in EGA, PGA, SJC, TJC, and ESR, indicating superior clinical improvement in the exposed group (P<0.01). The incidence of abnormal γ-glutamyl transferase and creatinine levels were higher in the control group than in the exposed group (P<0.01 or P<0.05), while no significant differences were observed in other safety indicators between the two groups (P>0.05).

Conclusion: Biqi Capsules combined with conventional treatment of Western medicine effectively reduce RA disease activity, lower inflammation levels, relieve clinical symptoms, and do not increase the incidence of adverse events. (Registration No. NCT05219214).

Objective: To investigate the ameliorative effects of quercetin (QE) on spermatogenic function and elucidate the underlying molecular mechanisms in vivo.

Methods: Thirty male C57BL/6 mice (6-8 weeks old) were randomly divided into 5 groups using a random number (n=6 per group): control, triptolide (TP) model (0.1 mg/kg per day), and different doses of quercetin (QE) treatment groups (25, 50, and 100 mg/kg per day, intragastrically). Except for controls, all mice received TP to induce spermatogenic impairment, with concurrent QE administration in treatment groups. The intervention lasted 35 days, covering 1 complete spermatogenic cycle, and mice were euthanized on day 38. Histopathological damage and apoptosis in spermatogenic cells were evaluated using hematoxylin and eosin (H&E) staining, TUNEL assay, and Western blot analysis for Bcl-2, Bax, and cleaved caspase-9. Blood-testis barrier (BTB) integrity was assessed by immunofluorescence and Western blot for tight junction proteins, including zonula occludens-1 (ZO-1) and junctional adhesion molecule A (JAMA). The PI3K/AKT signaling pathway was investigated through Western blot analysis of PI3K, AKT, and phosphorylated AKT (p-AKT). Network pharmacology and molecular docking simulations were performed to predict QE's molecular mechanisms, followed by experimental verification.

Results: QE treatment significantly ameliorated TP-induced testicular damage, increased spermatogenic epithelial thickness and spermatogonial tubule diameter, and decreased apoptosis of spermatogenic cells (P<0.05 or P<0.01). QE also improved the distribution and expression of key BTB proteins, including ZO-1 and JAMA (P<0.05 or P<0.01). Network pharmacology and molecular docking studies suggested that QE influences the PI3K-AKT signaling pathway, which was confirmed by increased AKT phosphorylation levels observed in Western blot results (P<0.05 or P<0.01).

Conclusions: QE can mitigate TP-induced spermatogenic dysfunction, reduce apoptosis of spermatogenic cells, and preserve BTB structural integrity by upregulating the PI3K-AKT signaling pathway. QE may be a potential therapeutic agent for treating TP-induced spermatogenic disorders.