Objective This study aims to explore the potential anti-cancer properties of boric acid (BA) in human endometrial cancer Ishikawa cells by assessing its influence on cell viability, apoptosis, oxidative stress, and inflammatory responses. Methods The impact of BA at concentrations ranging from 2.5 to 100 mM on cell viability was assessed in Ishikawa cells and normal fibroblast L929 cells (used as the control) through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Spectrophotometric measurements were performed to determine the total oxidant status (TOS) and total antioxidant status (TAS) in BA-treated cells, and the oxidative stress index (OSI) was calculated. The enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of cytochrome c and caspase 3, both of which are constituents of the extrinsic apoptotic pathway. Furthermore, changes in the concentrations of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) in the cells were analyzed using ELISA and immunofluorescence staining. Results The exposure of Ishikawa cells to BA for 24 hours led to a dose-dependent decline in cell viability, with an IC50 value of 40 mM. BA dose-dependently increased cytochrome c and caspase 3 levels in cancer cells. In Ishikawa cells, BA treatment led to a significant elevation in OSI. Moreover, the concentrations of TNF-α and IL-1β exhibited a dose-dependent decrease in BA-treated cells. On the other hand, in L929 cells, BA decreased OSI in a dose-dependent manner but did not change TNF-α and IL-1β levels. Concentrations up to 80 mM had no effect on cell viability and apoptosis, but BA at 80 mM concentration decreased viability and increased cytochrome c and caspase 3 levels in L929 cells. Conclusion BA inhibited cell viability, triggered apoptosis, induced oxidative stress, and suppressed inflammatory responses in endometrial cancer cells. Notably, at its IC50 concentration, BA had no cytotoxic effect on normal fibroblasts. Given its favorable properties, BA may provide a valuable therapeutic option to impede the development and progression of endometrial cancer.

Heat shock protein 90 (Hsp90) inhibitor and cannabinoid agonists ameliorate dry skin-induced chronic itch. We have recently reported that cannabinoids, hsp90 and nitric oxide (NO) are involved in dry skin-induced itch. Here, we investigated the contribution of the Th2 cell signaling pathway to the antipruritic effect of the hsp90 inhibitor 17-Alilamino-17-demethoxygeldanamycin (17-AAG), nitric oxide synthase (NOS) inhibitor Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and cannabinoid agonist WIN 55,212–2 on a dry skin-induced scratch. Dry skin-induced chronic itching was created by topical application of AEW (acetone/diethyl ether/water). WIN 55,212–2 (1 mg/kg, i.p.), L-NAME (1 mg/kg, i.p.) and increasing doses of 17-AAG (1, 3 and 5 mg/kg,i.p.) were administered to Balb/c mice (for each group, n = 6). After these applications, skin tissues were taken from the nape region of all of the mice. Gene and protein expressions of IL-13 and IL-31 were evaluated in skin tissues by RT-PCR and immunohistochemistry, respectively. IL-13 and IL-31 mRNA expressions and immune positive cell counts were increased in the AEW applied groups. WIN 55,212–2 reduced both of the increased cytokines levels, while L-NAME decreased only the IL-13. 17-AAG dose-dependently reduced the increased cytokine levels. IL-13 and IL-31 levels significantly decreased following the co-administration of these agents. These results show that increased levels of IL-13 and IL-31 are associated with pruritus. Hsp90 inhibition and cannabinoid system activation may induce antipruritic effects through down-regulation of these cytokines.

We investigated microtubule-associated protein 2 (MAP-2) immunoreactivity of hippocampal neurons and the potential role of royal jelly (RJ) in regulating MAP-2 during experimental hypothyroidism (HT). Thirty adult female Wistar albino rats were randomized into five groups: the control group was untreated, the sham control group was treated with 10 mg/kg 0.9% sterile saline injected intraperitoneally (i.p.), The RJ group was treated with 100 mg/kg RJ by oral gavage, the HT group was treated with 10 mg/kg propylthiouracil (PTU) i.p. to induce experimental hypothyroidism, and the HT + RJ group was treated with 10 mg/kg PTU i.p. + 100 mg/kg RJ by oral gavage. Oral and i.p. administrations were performed once daily for 20 days. Thyroid stimulating hormone (TSH) and free thyroxine (fT4) levels in the serum were measured biochemically, MAP-2 was measured immunohistochemically in the hippocampus and an immunohistochemical H score was calculated. MAP-2 immunoreactivity appeared in the cytoplasm of neuron cell bodies and dendrites in the hippocampal CA3 and CA1 regions in the control, sham control and RJ groups. MAP-2 immunoreactivity decreased significiantly in the HT group compared to control, sham control and RJ groups. Also, vascular dilation and swollen cells were observed following PTU administration. The degeneration that was observed in the HT group decreased by RJ administration. By contrast, MAP-2 immunoreactivity increased following administration of RJ. Experimental hypothyroidism reduced significiantly MAP-2 immunoreactivity in both the CA3 and CA1 regions and caused degeneration, including edema and vascular dilation, in the hippocampus. RJ increased MAP-2 expression and exhibited a therapeutic effect on the degenerative changes.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder characterized by cystic ovarian morphology, anovulation, and infertility. Ovarian fibrosis has recently emerged as a key pathological feature of PCOS. This study investigated whether pirfenidone (PFD), an antifibrotic agent, could improve ovarian dysfunction in a letrozole-induced PCOS rat model. Forty-two female Wistar albino rats were divided into six groups (n=7 each): control, PFD, PCOS, PCOS/PFD, PCOS/combined oral contraceptives (COC), and PCOS/PFD/COC. PCOS was induced using letrozole (1 mg/kg/day orally for 21 days). PFD (200 mg/kg/day) and/or COC (0.18 mg/kg cyproterone acetate and 0.00315 mg/kg ethinyl estradiol) were administered for 21 days. Compared to controls, PCOS rats exhibited significant disruptions in estrous cyclicity, ovarian morphology, and fibrosis-related markers (all p<0.0001), despite no significant changes in testosterone (p=0.058) or estrogen (p=0.896) levels. PFD treatment significantly improved estrous cyclicity, follicular profile, and corpora lutea count (all p<0.0001), reduced ovarian fibrosis (p<0.0001), downregulated TGF-β1, CTGF, and MMP-9 (all p<0.0001), and upregulated PPAR-γ and MMP-2 (both p<0.0001), without affecting hormone levels (p=0.945 and p=0.479, respectively). COC treatment also improved estrous cyclicity and ovarian histology (all p<0.0001), reduced fibrosis (p=0.005), and modulated TGF-β1, CTGF, MMP-9, and PPAR-γ expression (p=0.0001 to <0.0001), but had no effect on MMP-2 (p=0.868). Combination therapy (PCOS/PFD/COC) provided additional improvement in corpora lutea count (p0.05). These findings suggest that pirfenidone mitigates PCOS pathology by targeting ovarian fibrosis, supporting antifibrotic therapy as a novel and promising approach.