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The anti-tumor activity of diosgenin, a new steroidal constituent present in fenugreek, on two human breast cancer cell lines, MCF-7 and Hs578T, was studied. Diosgenin treatment resulted in cell growth inhibition, cell cycle arrest, and apoptosis in concentration- and time-dependent manners in both cell lines. Western blot analyses of whole cell lysates for cell cycle proteins showed that diosgenin altered phosphorylated cyclin checkpoint1 (p-Chk1Ser345) and cyclin B expression, which resulted in G2/M phase blockade. Mechanistically, Cdc25C-Cdc2 signaling was involved in inactivating Chk1Ser345 by p53-dependence in MCF-7 cells and p21-dependence in Hs578T cells that are p53-deficient. Moreover, diosgenin induced a significant loss of the mitochondrial membrane potential in breast cancer cells, and prominently affected cell death through down-regulation of the anti-apoptotic protein, Bcl-2. This released cytochrome c and activated the caspase signaling cascade. Taken together, these findings reveal that the anti-proliferative activity of diosgenin involves the induction of G2/M phase arrest via modulating the Cdc25C-Cdc2-cyclin B pathway and mitochondria-mediated apoptosis in human breast cancer cell lines. This suggests the potential usefulness of diosgenin in treating breast cancer.

We evaluated the therapeutic outcome of intravitreal injection (IVI) of ganciclovir with/without oral valganciclovir for cytomegalovirus (CMV) anterior segment infection. We enrolled 61 patients (61 eyes) with PCR-proven CMV anterior segment infection. IVI of ganciclovir (2 mg/0.05 mL) was given as a loading dose; subsequent use of oral valganciclovir (900 mg twice daily) was determined according to the severity of anterior chamber inflammation after injection. All eyes had IVI of ganciclovir, and 53 patients received oral valganciclovir as adjunctive therapy with a mean duration of 1.9 months to achieve disease remission. Repeated diagnostic aqueous taps were performed in 37 eyes with suspected recurrence, and CMV DNA was positive in 24 eyes. This therapeutic strategy afforded a median 50% recurrence-free survival time of 47.0 ± 8.12 months. The patients’ mean best corrected visual acuity, intraocular pressure and corneal endothelial cell counts stabilized or improved. Corneal transplantation before CMV infection diagnosis was identified as an independent risk factor for recurrence (hazard ratio 6.81, 95% confidence interval 1.21–38.23, P  = 0.029). In patients with CMV anterior segment infection, the relative short-term therapeutic strategy, IVI of ganciclovir in adjunction with/without oral valganciclovir, effectively achieved a median recurrence-free survival time of nearly 4 years.

Problem: Acquired melanocytic nevi are common benign pigmented cutaneous neoplasms. Traditional treatment of acquired melanocytic nevi includes dermabrasion, electrodesiccation and surgical excision. During recent years, laser therapy has become increasingly popular for the removal of acquired melanocytic nevi. Erbium-doped yttrium aluminum garnet laser emits a wavelength of 2,940 nm which is absorbed by tissue water. It can ablate and remove the superficial cutaneous lesions.[1] Although erbium-doped yttrium aluminum garnet laser is considered an effective and safe method for treatment of acquired melanocytic nevi, the therapeutic depth is often difficult to control.[2] Moreover, if depth of the treated area is not sufficient, the nevus would recur soon after treatment. On the other hand, scar formation would develop if the treated depth is more. Therefore, we have tried to find a solution to improve the outcome of laser procedure. Solution: Dermoscopy is a non-invasive technique which has been used for assisting the diagnosis of pigmented or nonpigmented skin tumors for decades. We performed intra-therapeutic dermoscopy examination to enhance the clearance of melanocytic nevi by laser therapy.

Objective We aim to compare the effect of long-term anti-seizure medication (ASM) monotherapy on the risk of death and new ischemic stroke in patients with post-stroke epilepsy (PSE). Patients and methods We identified all hospitalized patients (≥ 20 years) with a primary diagnosis of ischemic or hemorrhagic stroke from 2001 to 2012 using the National Health Insurance Research Database in Taiwan. The PSE cohort were defined as the stroke patients (1) who had no epilepsy and no ASMs use before the index stroke, and (2) who had epilepsy and ASMs use after 14 days from the stroke onset. The patients with PSE receiving ASM monotherapy were enrolled and were categorized into phenytoin, valproic acid, carbamazepine, and new ASM groups. We employed the Cox regression model to estimate the unadjusted and adjusted hazard ratios (HRs) with 95 % confidence intervals (CIs) of death and new ischemic stroke within 5 years across all groups, using the new ASM group as the reference. Results Of 6962 patients with PSE using ASM monotherapy, 3917 (56 %) were on phenytoin, 1623 (23 %) on valproic acid, 457 (7 %) on carbamazepine, and 965 (14 %) on new ASMs. After adjusting for confounders, compared with new ASM users, phenytoin users had a higher risk of death in 5 years (HR: 1.64; 95 % CI: 1.06–2.55). On the other hand, all ASM groups showed a similar risk of new ischemic stroke in 5 years. Conclusions Among patients with PSE on first-line monotherapy, compared to new ASMs, use of phenytoin was associated with a higher risk of death in 5 years.

Purpose: To evaluate the performance of deep learning (DL) in diagnosing glaucoma and predicting its progression using fundus photography and retinal optical coherence tomography (OCT) images. Materials and Methods: Relevant studies published up to 30 October 2024 were retrieved from PubMed, Medline, EMBASE, Cochrane Library, Web of Science, and ClinicalKey. A bivariate random-effects model was employed to calculate pooled sensitivity, specificity, positive and negative likelihood ratios, and area under the receiver operating characteristic curve (AUROC). Results: A total of 48 studies were included in the meta-analysis. DL algorithms demonstrated high diagnostic performance in glaucoma detection using fundus photography and OCT images. For fundus photography, the pooled sensitivity and specificity were 0.92 (95% CI: 0.89–0.94) and 0.93 (95% CI: 0.90–0.95), respectively, with an AUROC of 0.90 (95% CI: 0.88–0.92). For the OCT imaging, the pooled sensitivity and specificity were 0.90 (95% CI: 0.84–0.94) and 0.87 (95% CI: 0.81–0.91), respectively, with an AUROC of 0.86 (95% CI: 0.83–0.90). In predicting glaucoma progression, DL models generally showed less robust performance, with pooled sensitivities and specificities ranging lower than in diagnostic tasks. Internal validation datasets showed higher accuracy than external validation datasets. Conclusions: DL algorithms achieve excellent performance in diagnosing glaucoma using fundus photography and OCT imaging. To enhance the prediction of glaucoma progression, future DL models should integrate multimodal data, including functional assessments, such as visual field measurements, and undergo extensive validation in real-world clinical settings.

To evaluate efficacy and safety of picosecond 755 nm alexandrite laser as compared to 1064 nm QS-Nd:YAG laser for melasma treatment in Asians. Twelve patients received 4 sessions of treatments at 1-month interval in a split-face manner. The right side of each patient’s face received 755 nm picosecond laser, and the other side received 1064 nm QS-Nd:YAG laser. Zoom handpiece of 755 nm picosecond laser at fluence of 0.88–1.18 J/cm2 was applied. The treatment protocol used for 1064 nm QS-Nd:YAG laser was 8 mm spot size at fluence of 2.0 J/cm2 initially followed by 6 mm spot size at fluence of 3.5 J/cm2, and finishing with 4 mm spot size at 3.2 J/cm2. For both 755 nm picosecond laser and 1064 nm QS-Nd:YAG laser, the endpoint was mild erythema and swelling without petechiae. Objective evaluation with visual analogue score was conducted by two independent physicians. Subject self-assessment for each patient was conducted as well. Statistical results showed that higher pigmentation clearance rate was achieved at the 755 nm picosecond laser side after the second treatment. At the 3 months follow-up, greater clearance was observed at the 755 nm picosecond laser side compared to the 1064 nm QS-Nd:YAG side. 755 nm alexandrite picosecond laser has been observed to achieve a faster and better clearance rate for melasma compared to 1064 nm QS-Nd:YAG laser. We conclude that the 755 nm picosecond laser could be a safe and effective modality for melasma treatment in Asians.

Simple SummaryThe C-X-C motif chemokine receptor 4 (CXCR4) is overexpressed in various cancer stem/progenitor cells via activation of the epithelial-mesenchymal transition (EMT) program to facilitate tumor cell aggressiveness in the premetastatic niche. Through miRNAs microarray and bioinformatics analysis, we confirmed that miR-139 directly interacted with the 3′-untranslated region (3′-UTR) of CXCR4. Overexpression of miR-139 down-modulated CXCR4/p-Akt axis to attenuate invasion and migration of human breast cancer stem cells both in vitro and in vivo. Furthermore, miR-139 expression assessed by quantitative real-time PCR (qRT-PCR) in laser capture microdissected tumor samples significantly correlated with more advanced tumors in patients with breast cancer. Our findings provide support to account for the preferential role of miR-139 in interrupting breast cancer progression, identifying miR-139 as a potential biomarker in prediction of breast cancer invasiveness.AbstractElevated expression of C-X-C motif chemokine receptor 4 (CXCR4) correlates with chemotaxis, invasion, and cancer stem cell (CSC) properties within several solid-tumor malignancies. Recent studies reported that microRNA (miRNA) modulates the stemness of embryonic stem cells. We aimed to investigate the role of miRNA, via CXCR4-modulation, on CSC properties in breast cancer using cell lines and xenotransplantation mouse model and evaluated miR-193 levels in 191 patients with invasive ductal carcinoma. We validated miR-139 directly targets the 3′-untranslated region of CXCR4. Hoechst 33342 fluorescence-activated cell sorting (FACS) and sphere-forming assay were used to identify CSCs. MiR-139 suppressed breast CSCs with mesenchymal traits; led to decreased migration and invasion abilities through down-regulating CXCR4/p-Akt signaling. In lung cancer xenograft model of nude mice transplanted with human miR-139-carrying MDA-MB-231 cells, metastatic lung nodules were suppressed. Clinically, microdissected breast tumor tissues showed miR-139 reduction, compared to adjacent non-tumor tissues, that was significantly associated with worse clinicopathological features, including larger tumor size, advanced tumor stage and lymph node metastasis; moreover, reduced miR-139 level was predominately occurred in late-stage HER2-overexpression tumors. Collectively, our findings highlight miR-139-mediated suppression of CXCR4/p-Akt signaling and thereby affected mesenchymal stem-cell genesis, indicating its potential as a therapeutic target for invasive breast cancer.