Tioconazole

This study aimed to investigate the clinical efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the treatment of high-risk cervical low-grade squamous intraepithelial lesion (LSIL) and to analyze the influence of different risk factors on the efficacy.

The clinical data of 173 patients with persistent cervical LSIL and high-risk human papillomavirus (HR-HPV) infection were retrospectively analyzed. After treatment, HPV and TCT were reexamined every 3 months, and colposcopic biopsy was performed if necessary.

At 6 months of follow-up, the HPV clearance rate, complete remission (CR) rate, persistence rate, and progression rate were 73.41%, 89.60%, 8.09%, and 2.31%, respectively. The HPV clearance rate showed an upward trend with time. Moreover, the CR rates of patients with 41-50 years old group, positive HPV16/18 genotyping, and type 3 transformation zone (TZ) were 77.14%, 84.52%, and 83.33%, respectively; these rates were significantly lower compared to patients without the corresponding high-risk factors (P = 0.021, 0.045, 0.042), but had no significant effect on HPV clearance rate. A subgroup analysis based on TCT results revealed no significant effect on the efficacy of ALA-PDT in the treatment of high-risk cervical LSIL. Furthermore, the 6-month CR rate and 2-year HPV clearance rate of the patients with both positive HPV16/18 genotyping and TZ3 were significantly lower than those of the patients without the two high-risk factors (73.53% vs. 94.74%, P = 0.010; 78.95% vs. 97.67%, P = 0.028, respectively).

ALA-PDT is a safe and effective treatment for high-risk cervical LSIL. Its efficacy could be affected by patient age, HPV type, and cervical TZ type.

Sterol 12α-hydroxylase (CYP8B1) is a key regulator of bile acid (BA) homeostasis and an emerging therapeutic target for metabolic disorders. To address the challenge of cellular CYP8B1 inhibition characterization, this work developed a pharmacologically optimized HepG2 cells model using triiodothyronine-dexamethasone-bezafibrate (TDB) induction, which significantly enhances the 12α-hydroxylation activity along the acidic pathway of BA biosynthesis in HepG2 cells. Employing stable isotope tracing with apolipoprotein A1-solubilized 2,3,4-¹³C₃-cholesterol, we established a liquid chromatography-mass spectrometry-based flux analysis platform to track de novo BA synthesis. Combined with a recombinant CYP8B1 assay, flux analysis revealed that CYP8B1 participates in cholic acid synthesis in HepG2 cells, typically via 12α-hydroxylation of 7α-hydroxy-3-oxo-4-cholestenoic acid and dihydroxycholestanoic acid. In TDB-HepG2 cells, azole antifungals exhibited differentiated inhibition of 12α-hydroxylation activity, generally mirroring the enzymatic data. Econazole acted as a relatively selective CYP8B1 inhibitor with a cellular half-maximal inhibitory concentration of 0.31-0.45 μM, tioconazole and posaconazole dually inhibited CYP8B1 and sterol 27-hydroxylase (CYP27A1), itraconazole and voriconazole primarily inhibited CYP27A1, and fluconazole showed no activity toward either enzyme. This study provides the first direct evidence that CYP8B1 participates in cholic acid synthesis via the acidic pathway and establishes a high-throughput cellular platform for screening CYP8B1 inhibitors, revealing azoles as effective modulators of this pathway. SIGNIFICANCE STATEMENT: Optimized HepG2 model using a ¹³C₃-cholesterol flux assay provides direct evidence that CYP8B1 participates in cholic acid biosynthesis via the acidic pathway and establishes a high-throughput cellular platform for screening CYP8B1 inhibitors, revealing azoles as effective modulators of this pathway.