ZBTB28 inhibits breast cancer by activating IFNAR and dual blocking CD24 and CD47 to enhance macrophages phagocytosis.

Breast cancer is the leading cause of cancer death in female. Until now, advanced breast cancer is still lack effective treatment strategies and reliable prognostic markers. In the present article, we introduced the physiologic and pathologic functions and regulation mechanisms of ZBTB28, a tumor suppressor gene, in breast cancer. ZBTB28 is frequently silenced in breast cancer due to promoter CpG methylation, and its expression is positively correlated with breast cancer patient survival. The antineoplastic effect of ZBTB28 in breast cancer was elucidated through a series of in vitro and in vivo measurements, including cell proliferation, apoptosis, cell cycle, epithelial mesenchymal transition (EMT), and growth of xenografts. Furthermore, ZBTB28 can directly regulate IFNAR to activate interferon-stimulated genes and potentiate macrophage activation. Ectopic ZBTB28 expression in breast cancer cells was sufficient to downregulate CD24 and CD47 to promote phagocytosis of macrophages, demonstrating that ZBTB28 was beneficial for the combination treatment of anti-CD24 and anti-CD47. Collectively, our results reveal a mode of action of ZBTB28 as a tumor suppressor gene and suggest that ZBTB28 is an important regulator of macrophage phagocytosis in breast cancer, holding promise for the development of novel therapy strategies for breast cancer patients.

Myopia prevalence and ocular biometry in children and adolescents at different altitudes: a cross-sectional study in Chongqing and Tibet, China.

OBJECTIVE: To investigate the differences in myopia prevalence and ocular biometry in children and adolescents in Chongqing and Tibet, China. DESIGN: Cross-sectional study. SETTING: The study included children and adolescents aged 6-18 years in Chongqing, a low-altitude region, and in Qamdo, a high-altitude region of Tibet. PARTICIPANTS: A total of 448 participants in Qamdo, Tibet, and 748 participants in Chongqing were enrolled in this study. METHODS: All participants underwent uncorrected visual acuity assessment, non-cycloplegic refraction, axial length (AL) measurement, intraocular pressure (IOP) measurement and corneal tomography. And the participants were grouped according to age (6-8, 9-11, 12-14 and 15-18 years group), and altitude of location (primary school students: group A (average altitude: 325 m), group B (average altitude: 2300 m), group C (average altitude: 3250 and 3170 m) and group D (average altitude: 3870 m)). RESULTS: There was no statistical difference in mean age (12.09±3.15 vs 12.2±3.10, p=0.549) and sex distribution (males, 50.4% vs 47.6%, p=0.339) between the two groups. The Tibet group presented greater spherical equivalent (SE, -0.63 (-2.00, 0.13) vs -0.88 (-2.88, -0.13), p<0.001), shorter AL (23.45±1.02 vs 23.92±1.19, p<0.001), lower prevalence of myopia (39.7% vs 47.6%, p=0.008) and flatter mean curvature power of the cornea (Km, 43.06±1.4 vs 43.26±1.36, p=0.014) than the Chongqing group. Further analysis based on age subgroups revealed that the Tibet group had a lower prevalence of myopia and higher SE in the 12-14, and 15-18 years old groups, shorter AL in the 9-11, 12-14 and 15-18 years old groups, and lower AL to corneal radius of curvature ratio (AL/CR) in all age subgroups compared with the Chongqing group, while Km was similar between the two groups in each age subgroup. Simple linear regression analysis showed that SE decreased with age in both the Tibet and Chongqing groups, with the Tibet group exhibiting a slower rate of decrease (p<0.001). AL and AL/CR increased with age in both the Tibet and Chongqing groups, but the rate of increase was slower in the Tibet group (p<0.001 of both). Multiple linear regression analysis revealed that AL had the greatest effect on SE in both groups, followed by Km. In addition, the children and adolescents in Tibet presented thinner corneal thickness (CCT, p<0.001), smaller white to white distance (WTW, p<0.001), lower IOP (p<0.001) and deeper anterior chamber depth (ACD, p=0.015) than in Chongqing. Comparison of altitude subgroups showed that the prevalence of myopia (p=0.002), SE (p=0.031), AL (p=0.001) and AL/CR (p<0.001) of children at different altitudes was statistically different but the Km (p=0.189) were similar. The highest altitude, Tengchen County, exhibited the lowest prevalence of myopia and greatest SE among children, and the mean AL also decreased with increasing altitude. CONCLUSIONS: Myopia prevalence in Tibet was comparable with that in Chongqing for students aged 6-8 and 9-11 years but was lower and myopia progressed more slowly for students aged 12-14 and 15-18 years than in Chongqing, and AL was the main contributor for this difference, which may be related to higher ultraviolet radiation exposure and lower IOP in children and adolescents at high altitude in Tibet. Differences in AL and AL/CR between Tibet and Chongqing children and adolescents manifested earlier than in SE, underscoring the importance of AL measurement in myopia screening.

Evaluation of childhood developing via optical coherence tomography-angiography in Qamdo, Tibet, China: A prospective cross-sectional, school-based study.

BACKGROUND: Optical coherence tomography angiography (OCTA) is a new and reliable machine used to evaluate retinal structure and macular perfusion in children. The use of OCTA under bad condition such as high altitude, low atmospheric oxygen, and low humidity, in children is rarely. AIM: To quantify the macular micro-vasculature in healthy children of various ages using OCTA in Qamdo. METHODS: Design: Prospective cross-sectional, school-based study. Three hundred and forty-seven normal students from 9 schools in 4 different areas in Qamdo were included. OCTA was performed on a 3 mm × 3 mm area centered on the macular region and macular cube 512 × 128 showed details in macular. Early treatment of diabetic retinopathy study Vessel Flow Density (VD) of the macular central vascular plexus density (CVD), inner vascular plexus density (IVD), full vascular plexus density (FVD), and the size of the foveal avascular zone (FAZ) were measured. All these results corrected by t/s = 3.382 × 0.01306 × (axial length-1.82). The differences were compared among various ages, sexes and living environments. RESULTS: The mean FAZ area in all eyes was 0.27 mm2 ± 0.12 mm2. The mean foveal thickness (MFT) in the macular cube was 227.64 µm ± 23.51 µm. Compared with girls, boys had a lager FAZ (P = 0.0029). Among the different age groups, MFT (P < 0.001) and FVD (P < 0.0001), IVD (P < 0.0001), and CVD (P = 0.0050) increased with age. FAZ areas were not correlated with age (P = 0.8853) or others (MFT, area). CONCLUSION: OCTA can use to evaluate macular perfusion in children. Our data bridge the gap between structural OCT and perfusion density in children in high altitude. Even though these were not a longitudinal study, it may provide us with hints about retina development during puberty and clinical implications of OCTA in children.

Effectiveness and the nomogram of small incision lenticule extraction in the correction of myopic anisometropia in adults.

AIM: To evaluate the safety, effectiveness, and predictability of small incision lenticule extraction (SMILE) for the treatment of anisometropia, and to explore the personalized design scheme of SMILE in correcting adult myopia anisometropia based on the nomogram. METHODS: It's a prospective cohort study. Patients with anisometropic myopia of refractive difference ≥ 2.0 diopters (D) who underwent SMILE between September 2020 and March 2021 were enrolled. Clinical features and visual function were assessed preoperatively and at 1wk, 1, 3, and 6mo after the operation. The examination included tests for uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refractive errors, effectiveness index (preoperative CDVA/postoperative UDVA), safety index (postoperative CDVA/preoperative CDVA), nomogram and stereoscopic function. Paired t-test, Wilcoxon signed-rank test and repeated-measures analyses of variance were used for continuous variables, and Pearson Chi-squared test was used for categorical variables. RESULTS: The study involved 45 consecutive patients (average age: 25.0±6.9y; 82 out of 90 eyes underwent SMILE, while 8 eyes were not operated). The average preoperative spherical equivalent (SE) was -4.74±0.22 D. Six months after surgery, the effectiveness index was 1.05±0.12, and the safety index was 1.09±0.11. Seventy eyes (85.4%) exhibited SE correction error within ±0.5 D. The percentage of eyes with Titmus stereoscopic function equal to or less than 200″ significantly increased from 55.6% preoperatively to 88.9% postoperatively (P<0.05). There was statistically significant difference between higher myopia eyes and contralateral eyes in average nomogram value/spherical refraction ratio. CONCLUSION: SMILE is safe, effective and predictable in correcting myopic anisometropia, and it improves stereoscopic visual function of anisometropia patients. The precise and individualized design of the nomogram is a vital element to ensure the balance of both eyes after SMILE.

Analysis of the Effectiveness of SMILE, FS-LASIK, and SBK in Myopic Patients and the Impact in UCVA and Tear Film Stability.

The aim of the present study was to investigate the effect of femtosecond laser small incision stromal lens extraction (SMILE), femtosecond laser-assisted excimer laser keratomileusis (FS-LASIK), and anterior elastic sublaminar laser keratomileusis (SBK) in myopic patients, and their effects on uncorrected visual acuity (UCVA) and tear film stability. 600 myopic patients admitted to our hospital from January 2020 to December 2021 were selected for the study and divided into SMILE group (200 patients, SMILE treatment), FS-LASIK group (200 patients, FS-LASIK treatment), and SBK group (200 patients, SBK treatment) according to the random number table method. Uncorrected visual acuity (UCVA), tear breakup time (BUT), tear secretion function test (Sit), and corneal higher-order image aberration global higher-order aberration (HOAS) were compared among the three groups. The UCVA values before operation, 2 weeks after operation, 1 month after operation, and 3 months after operation in the three groups were similar, and the BUT, Sit value, and HOAS of corneal higher-order image difference in the three groups were similar, and the differences were not statistically significant (P > 0.05). The BUT, Sit value, and HOAS of corneal higher-order image difference at 1 and 3 months after surgery in the SMILE group were higher than those in the FS-LASIK and SBK groups, and the differences were statistically significant (P < 0.05). SMILE, FS-LASIK, and SBK are effective in the treatment of myopia, which can effectively improve the uncorrected visual acuity and help the patients to recover their normal visual ability, but SMILE is more effective in tear film stability and corneal higher-order aberrations.

Corneal morphological changes after small incision lenticule extraction for myopic anisometropia.

Purpose: This research aims to study the corneal morphological changes in adult patients with myopic anisometropia after small incision lenticule extraction (SMILE) and the safety, efficacy, and predictability of clinical outcomes. Methods: This was a prospective cohort study. Patients with myopic anisometropia [refractive difference >2.0 diopters (D)] were included in this study who underwent SMILE at our hospital from September 2019 to March 2021. For the two eyes of each patient, the one with higher myopia was defined as group A, and the fellow eye was group B. The follow-up time points were set as 1 week, 1 month, 3 months, and 6 months after the surgery. The data collected were uncorrected and best-corrected distance visual acuity (UDVA and CDVA), spherical equivalent (SE), efficacy and safety indexes, posterior corneal elevation (PCE), anterior and posterior corneal radius of curvature in the 3 mm area at the center of the thinnest point of the cornea (ARC and PRC), and higher-order aberrations (HOAs). Results: The study included 36 patients (72 eyes), and the mean age was 25.2 ± 6.4 years. The preoperative SEs were -6.45 ± 1.25 D in group A and -3.76 ± 1.29 D in group B. Six months after surgery, the SEs in groups A and B were -0.09 ± 0.50 D and 0.07 ± 0.47 (P = 0.059), respectively. The efficacy indexes were 1.06 ± 0.16 in group A and 1.07 ± 0.14 in group B (P = 0.750). The safety indexes were 1.08 ± 0.14 in group A and 1.12 ± 0.15 in group B (P = 0.173). The PCE was significantly reduced at 6 months after surgery in pagebreak both groups (P < 0.05). The ARC was significantly higher than before the surgery (P < 0.05) in the two groups. The two groups showed significant increases in total HOAs, coma 90°, and spherical aberrations (P < 0.05). Conclusion: SMILE is predictable, effective, and safe in correcting myopic anisometropia. The postoperative changes in HOAs are characteristic.

PCDH20 inhibits esophageal squamous cell carcinoma proliferation and migration by suppression of the mitogen-activated protein kinase 9/AKT/ß-catenin pathway.

Aberrant protocadherins (PCDHs) expression trigger tumor invasion and metastasis. PCDH20 anti-tumor functions in various tumor have been identified. Tumor suppression is due to Wnt/ß-catenin pathway antagonism and may be suppressed caused by PCDH20 downregulation through promotor methylation, whereas PCDH20 effects and regulation mechanism in esophageal squamous cell carcinoma (ESCC) remains elusive. We analyzed PCDH20 effects on ESCC and underlying action mechanisms for PCDH20. We test PCDH20 expression in ESCC tissues and cells by semi-quantitative PCR (RT-PCR) and q-PCR (real-time quantitative polymerase chain reaction). MSP (methylation-specific PCR) was carried out to assess the methylation of PCDH20 in ESCC cells and tissues. Anti-tumor effects of PCDH20 in vitro were assessed by clone formation assay, CCK8 assay, Transwell assay, and flow cytometry. Nude mice tumorigenicity was used to assess PCDH20 anti-tumor effect in vivo. Online database, qPCR, and Western blotting were used to identify the downregulation of MAP3K9 by PCDH20, associated with AKT/ß-catenin signaling inactivation. We found that PCDH20 expression was dramatically attenuated in esophageal cancer tissues and cells, maybe due to promotor methylation, and ectopic PCDH20 expression suppressed ESCC malignant biological phenotypes. PCDH20 exerted anti-tumor effects by MAP3K9 downregulation, which suppressed AKT/ß-catenin signaling in ESCC cells. Conclusion: PCDH20 was a tumor suppressor gene, which antagonized AKT/ß-catenin signaling pathway in ESCC by decreasing MAP3K9.

ZBTB28 induces autophagy by regulation of FIP200 and Bcl-XL facilitating cervical cancer cell apoptosis.

BACKGROUND: Among the common preventable cancers of women, cervical cancer has the highest morbidity. It is curable if detected at an early stage. However, reliable diagnostic and prognostic markers, which relate to physiologic and pathologic regulation of cervical cancer, are not available. In this study, one such potential marker, ZBTB28, was evaluated for its potential usefulness in cervical cancer assessment. METHODS: Public database analysis, reverse-transcription polymerase chain reaction (PCR), and methylation-specific PCR were employed to analyze ZBTB28 expression and promoter methylation. The importance of ZBTB28 in cervical cancer cells was assessed by cellular and molecular analysis in vitro and in vivo. RESULTS: This study assessed the anti-tumor effects of the transcription factor, ZBTB28, which is often silenced in cervical cancer due to CpG methylation of its promoter. We found ZBTB28 to directly affect cervical cancer cell proliferation, apoptosis, autophagy, and tumorigenesis. Also, it increased cancer cell chemosensitivity to Paclitaxel, Cisplatin, and 5-fluorouracil. Ectopic ZBTB28 expression inhibited the growth of cervical cancer xenografts in nude mice. Furthermore, electron microscopy demonstrated ZBTB28 to induce autophagosomes in cervical cancer cells. ZBTB28 induced cellular autophagy by the degradation of Bcl-XL, reduction of the Bcl-XL-BECN1 complex, and by interaction with the autophagy-related gene FIP200. ZBTB28-induced autophagy of cervical cancer cells was shown to mediate cellular apoptosis through the regulation of FIP200. CONCLUSION: These findings identify ZBTB28 as a tumor suppressor gene that can induce autophagy-related apoptosis in cervical cancer cells. As such, ZBTB28 may be a target for the treatment of uterine-cervical carcinoma. Further, ZBTB28 promoter methylation analysis may offer a new objective strategy for cervical cancer screening.