The protective role of water intake in age-related eye diseases: insights from a Mendelian randomization study.

Age-related eye diseases (AREDs), including age-related cataracts (ARCs), age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma, are a leading cause of visual loss globally. This study aimed to explore the effects of dietary water intake on AREDs using Mendelian randomization. In the European population, genome-wide association study (GWAS) summary statistics of water intake and AREDs were obtained from the UK Biobank database and the FinnGen Consortium, respectively. The causal associations between water intake and ARED risks were explored by univariable and multivariable MR analyses, followed by sensitivity analyses to test the robustness of the results and detect potential pleiotropy bias. Water intake was associated with reduced risks of ARCs (odds ratio [OR]: 0.61; 95% confidence interval [CI]: 0.46-0.83; P = 1.44 × 10-3) and DR (OR: 0.52; 95% CI: 0.36-0.76; P = 5.47 × 10-4), and a suggestive reduced risk of AMD (OR: 0.42; 95% CI: 0.20-0.88; P = 2.18 × 10-2). Water intake had no effect on glaucoma (OR: 1.16; 95% CI: 0.72-1.88; P = 0.549). After adjusting confounders, the causal effects of water intake on ARCs and DR persisted. Our study provides evidence of the preventive role of water intake in ARCs and DR from a genetic perspective.

The efficacy of botulinum toxin type A treatment and surgery for acute acquired comitant esotropia.

Aim: To compare the long-term efficiency of botulinum toxin type A (BTXA) injection and surgery on acute acquired comitant esotropia (AACE). Methods: This retrospective study enrolled patients with AACE from January 2020 to August 2022. The horizontal angle of deviation pre- and post-treatment was measured. Deviations in BTXA and surgical treatment were compared. The BTXA group was divided into adequate treatment (AT) and inadequate treatment (inAT) subgroup based on the deviation of no more than 4 prism diopters (at near and distance) or temporary exotropia at the 2 week follow-up. The two subgroups were compared to determine the long-term efficacy of BTXA treatment. Results: Ninety-two patients with AACE were included. Follow-up was 6 months. The deviations of the surgery and BTXA group were significantly smaller at the 6 month follow-up than at pre-treatment (p < 0.001). The deviation before treatment in the surgery group was larger than in the BTXA groups (p < 0.001) but smaller at the 6 month follow-up (p < 0.001). The deviation was similar in the AT-BTXA and inAT-BTXA subgroups before treatment (p = 0.322 for distance and p = 0.051 for near) but smaller in the AT-BTXA subgroup at 6 month follow-up (p < 0.001 for near and distance). Conclusion: Surgery and BTXA successfully treat AACE. Surgery has a more precise and lasting therapeutic effect than BTXA. AACE patients adequately treated with BTXA and with deviations of no more than 4 prism diopters at 2 weeks follow-up had better outcomes.

The association of postoperative radiotherapy with survival in resected N2 non-small cell lung cancer.

Background: The current staging system for completely resected pathologic N2 non-small cell lung cancer (NSCLC) treated with chemotherapy is not suitable for distinguishing those patients most likely to benefit from postoperative radiotherapy (PORT). This study aimed to construct a survival prediction model that will enable individualized prediction of the net survival benefit of PORT in patients with completely resected N2 NSCLC treated with chemotherapy. Methods: A total of 3,094 cases from between 2002 and 2014 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Patient characteristics were included as covariates, and their association with overall survival (OS) with and without PORT was assessed. Data from 602 patients from China were included for external validation. Results: Age, sex, the number of examined/positive lymph nodes, tumor size, the extent of surgery, and visceral pleural invasion (VPI) were significantly associated with OS (P<0.05). Two nomograms were developed based on clinical variables to estimate individuals' net survival difference attributable to PORT. The calibration curve showed excellent agreement between the OS predicted by the prediction model and that actually observed. In the training cohort, the C-index for OS was 0.619 [95% confidence interval (CI): 0.598-0.641] in the PORT group and 0.627 (95% CI: 0.605-0.648) in the non-PORT group. Results showed that PORT could improve OS [hazard ratio (HR): 0.861; P=0.044] for patients with a positive PORT net survival difference. Conclusions: Our practical survival prediction model can be used to make an individualized estimate of the net survival benefit of PORT for patients with completely resected N2 NSCLC who have been treated with chemotherapy.

Carboxymethyl Chitosan-Modified Graphene Oxide as a Multifunctional Vector for Deltamethrin Delivery and pH-Responsive Controlled Release, Enhanced Leaf Affinity, and Improved Mosquito-Killing Activity.

Traditional deltamethrin (DM) formulations (e.g., emulsifiable concentrates, wettable powders, etc.) have significant disadvantages of poor water dispersion stability, burst release, weak leaf affinity, short duration, poor efficacy, and high environmental toxicity. A nanomaterial-based pesticide delivery system (PDS) has provided effective strategies for green preparation and synergism of pesticide formulations. In this article, we developed carboxymethyl chitosan (CMCS)-modified graphene oxide (GO) as a vector for DM and constructed a pH-responsive PDS for Culex pipiens pallens control. GO-CMCS possesses excellent pesticide loading performance for DM (loading rate 87.76%). After being loading on GO-CMCS, the GO-CMCS-DM has a significantly improved dispersion stability in water. The GO-CMCS-DM exhibits pH-responsive controlled release performance, which can sustain the release of DM into the medium, maintaining an effective long-term concentration. Additionally, the leaf adhesion of GO-CMCS-DM is better than that for free DM, which can improve the pesticide utilization. Therefore, GO-CMCS-DM has a prolonged persistent period and sustained activity against Culex pipiens pallens. Considering the industrialization potential of GO, we believe that GO will play an important role in the pest control and antiepidemic fields.

Proposed clinical phases for the improvement of personalized treatment of checkpoint inhibitor-related pneumonitis.

Background: Checkpoint inhibitor-related pneumonitis (CIP) is a lethal immune-related adverse event. However, the development process of CIP, which may provide insight into more effective management, has not been extensively examined. Methods: We conducted a multicenter retrospective analysis of 56 patients who developed CIP. Clinical characteristics, radiological features, histologic features, and laboratory tests were analyzed. After a comprehensive analysis, we proposed acute, subacute, and chronic phases of CIP and summarized each phase's characteristics. Results: There were 51 patients in the acute phase, 22 in the subacute phase, and 11 in the chronic phase. The median interval time from the beginning of CIP to the different phases was calculated (acute phase: ≤4.9 weeks; subacute phase: 4.9~13.1 weeks; and chronic phase: ≥13.1 weeks). The symptoms relieved from the acute phase to the chronic phase, and the CIP grade and Performance Status score decreased (P<0.05). The main change in radiologic features was the absorption of the lesions, and 3 (3/11) patients in the chronic phase had persistent traction bronchiectasis. For histologic features, most patients had acute fibrinous pneumonitis in the acute phase (5/8), and most had organizing pneumonia in the subacute phase (5/6). Other histologic changes advanced over time, with the lesions entering a state of fibrosis. Moreover, the levels of interleukin-6, interleukin-10 and high-sensitivity C-reactive protein (hsCRP) increased in the acute phase and decreased as CIP progressed (IL-6: 17.9 vs. 9.8 vs. 5.7, P=0.018; IL-10: 4.6 vs 3.0 vs. 2.0, P=0.041; hsCRP: 88.2 vs. 19.4 vs. 14.4, P=0.005). Conclusions: The general development process of CIP can be divided into acute, subacute, and chronic phases, upon which a better management strategy might be based devised.

Environmentally Friendly Zr-Based MOF for Pesticide Delivery: Ultrahigh Loading Capacity, pH-Responsive Release, Improved Leaf Affinity, and Enhanced Antipest Activity.

The stimuli responsive pesticide delivery system (PDS) has drawn increasing attention in recent years, a system which can effectively improve the utilization of pesticides. In the current research, we report a pH responsive PDS by using carboxymethyl cellulose (CMC) modified Zr-based metal organic frameworks (UiO-66-NH2) as the nanocarrier for acetamiprid (ATP). UiO-66-NH2-CMC possesses a large surface area and abundant pores, which can effectively load ATP, and the loading rate is as high as 90.79%. Compared with free ATP, the ATP@UiO-66-NH2-CMC nanopesticide exhibits pH responsive controlled release behavior, and the pesticide can sustained release to the medium. In addition, it also shows improved leaf affinity, which makes it easier to wet the leaf surface and improve the utilization of pesticide. Therefore, ATP@UiO-66-NH2-CMC displays better antipest activity against aphids than free ATP does. Meanwhile, ATP@UiO-66-NH2-CMC shows no negative effects on the germination and growth of maize, showing good biosafety. Moreover, the ATP@UiO-66-NH2-CMC nanopesticide does not contain any toxic organic solvents or additives. Therefore, we hope that it can be a suitable candidate for plant protection and sustainable agriculture.

Metal-Organic Framework (UiO-66)-Based Temperature-Responsive Pesticide Delivery System for Controlled Release and Enhanced Insecticidal Performance against Spodoptera frugiperda.

Spodoptera frugiperda is a global pest that brings about great disasters to crops. Conventional pesticide formulations often suffer from poor water solubility, low stability, burst release, weak leaf adhesion, and low efficiency. To improve the insecticidal activity of pesticides, a stimuli-responsive controlled release pesticide delivery system (PDS) has attracted extensive attention in recent years. This paper reports a temperature-responsive controlled release PDS based on poly(N-isopropyl acrylamide) (PNIPAm)-modified indoxacarb (IDC)-loaded UiO-66-(COOH)2 (IDC@UiO-66-(COOH)2-PNIPAm) and studies its insecticidal activities against S. frugiperda. The UiO-66-(COOH)2 nanocarrier has an excellent pesticide loading performance, and the loading rate for IDC is 78.69%. The as-prepared PDS has good stability, temperature-responsive controllable release performance, and enhanced leaf affinity, so it can effectively improve the utilization rate of IDC. The insecticidal experiment indicates that the PDS has an enhanced control effect against S. frugiperda. In addition, biosafety analysis further verifies that the PDS exhibits no obvious negative effects on the germination of maize seeds and the growth of maize seedlings. In view of this, we believe that this PDS will have a broad application in the field of pesticide formulation innovation, pest management, and sustainable agricultural development.

Two-year longitudinal change in choroidal and retinal thickness in school-aged myopic children: exploratory analysis of clinical trials for myopia progression.

BACKGROUND: With increasing axial length and myopia progression, the micro-structure of the retina and choroid gradually changes. Our study describes the longitudinal changes in retinal and choroidal thickness in school-aged children with myopia and explores the relationship between changes in choroidal thickness and myopia progression. METHODS: An exploratory analysis of a randomized trial was performed. Children (n = 168, aged 7 to 12 years) with myopia from - 0.75 dioptre (D) to - 4.00 D were enrolled in this prospective longitudinal study. Cycloplegic refraction, axial length (AL), retinal and choroidal thicknesses were measured at baseline and at 1- and 2-year follow-ups. "Rapid progression myopia" was defined as increasing in myopia > 1.00 D and "stable progression myopia" was ≤ 1.00 D during the 2-year follow-up. Factors affecting the changes in choroidal thickness were analysed using linear mixed models. RESULTS: AL significantly increased by 0.67 ± 0.24 mm with a myopic shift of - 1.50 ± 0.64 D over the 2 years. The overall retinal thickness increased from 251.12 ± 15.91 µm at baseline to 253.47 ± 15.74 µm at the 2-year follow-up (F = 23.785, P < 0.001). The subfoveal choroidal thickness decreased from 231.03 ± 54.04 µm at baseline to 206.53 ± 59.71 µm at the 2-year follow-up (F = 73.358, P < 0.001). Choroidal thinning was significantly associated with AL elongation (ß = - 43.579 µm/mm, P = 0.002) and sex (ß = - 17.258, P = 0.001). Choroidal thickness continued to decrease in subjects with rapid progression (F = 92.06, P < 0.001) but not in those with steady progression (F = 2.23, P = 0.119). CONCLUSION: Significant choroidal thinning was observed and was associated with rapid progression and sex. These findings indicate a need to understand the role of the choroid in eye growth and myopia development. SYNOPSIS/PRECIS: The macular choroidal thickness of myopic children is relevant to different degrees of myopic progression in this 2-year longitudinal study. These findings suggest that control of choroidal thickness might work to regulate human ocular growth. Trial registration Chinese Clinical Trial Register (ChiCTR): ChiCTR-INR-16007722.

Pseudomonas simiae augments the tolerance to alkaline bauxite residue in Atriplex canescens by modulating photosynthesis, antioxidant defense enzymes, and compatible osmolytes.

In situ revegetation is effective in improving water-stable aggregation, preserving structural stability, and decreasing groundwater pollution to reduce the environmental risks posed by alkaline bauxite residue (ABR). Pseudomonas simiae, a plant growth-promoting rhizobacteria (PGPR), was used to promote Atriplex canescens growth challenged by ABR. The mechanism of P. simiae-induced plant growth promotion and tolerance against ABR stresses has been investigated. P. simiae was shown to alleviate ABR-induced stress in A. canescens by regulating photosynthesis and transpiration, inducing antioxidant defense, causing osmolyte accumulation, and altering plant morphology. Shoot dry weight, root dry weight, and root length of A. canescens were increased by 5.9%, 6.7%, and 11.5%, respectively, after inoculation with P. simiae for 60 days. Thus, it seems that P. simiae systemically regulated physiological processes in A. canescens favoring its growth under ABR treatments.

PDA@Ti3 C2 Tx as a novel carrier for pesticide delivery and its application in plant protection: NIR-responsive controlled release and sustained antipest activity.

BACKGROUND: Stimuli-responsive pesticide controlled release system provides a new strategy for the development of high-efficiency pesticides formulation. RESULTS: In this article, we report a novel polydopamine surface modified MXene-Ti3 C2 Tx nanocarrier for pesticide delivery and plant protection. Polydopamine modified Ti3 C2 Tx (PDA@Ti3 C2 Tx ) nanocarrier was prepared by biomimetic self-polymerization of dopamine on the surface of Ti3 C2 Tx . A typical pesticide, emamectin benzoate (EB), was loaded on PDA@Ti3 C2 Tx through physisorption process, with a high pesticide loading rate of 45.37%. PDA@Ti3 C2 Tx exhibited excellent photothermal conversion effect (η = 34.5%). Under the irradiation of near-infrared (NIR) laser, EB would sustained release from PDA@Ti3 C2 Tx nanocarrier to surrounding medium. Compared with free EB, EB@PDA@Ti3 C2 Tx exhibited prolonged persistence period, which can keep antipest activity at 14 days post spraying. In addition, PDA@Ti3 C2 Tx nanocarrier and EB@PDA@Ti3 C2 Tx nanoformulation are of good safety, showing no side effect to the seed germination and seedling growth. CONCLUSION: This research developed a novel nanocarrier for water-insoluble pesticide delivery, realizing NIR-responsive controlled release and sustained antipest activity.

Effect of the base-out recovery point as the surgical target for acute acquired comitant esotropia.

PURPOSE: To evaluate the treatment efficacy of the preoperative base-out recovery point as the surgical target angle for acute acquired comitant esotropia. METHODS: Prospective study. Twenty-two patients with acute acquired comitant esotropia (AACE) underwent strabismus surgery based on the target angle of the preoperative base-out recovery point. The postoperative deviation, positive fusional vergence, and negative fusional vergence were evaluated and compared with those of 23 normal individuals. RESULTS: The mean follow-up period was 18.68 ± 19.48 months. At the last follow-up, 19 (86.4%) of 22 subjects had orthophoria, whereas 3 (13.6%) had minimal esophoria. The postoperative angle of deviation was significantly smaller than the preoperative angle of deviation at near (P < 0.001) and distance (P < 0.001). Postoperative sensory fusion was significantly better than preoperative fusion at near (P < 0.001) and distance (P < 0.001). The postoperative stereoacuity improved significantly after the surgery at near (P < 0.001) and distance (P < 0.001). Compared with the controls, the convergence and divergence amplitudes in the AACE patients were similar at distance (P > 0.05) but were still narrower at near (P < 0.001). CONCLUSION: Good alignment and binocular balance were obtained with the surgical target angle of the base-out recovery point in AACE.

Correlation Between Increase of Axial Length and Height Growth in Chinese School-Age Children.

PURPOSE: To identify the relationship between the increase in axial length (AL) and height in school-age children and explore the influence of refractive status on such a relationship. METHODS: In this 5-year cohort study, 414 Chinese children (237 boys) aged 6-9 years (mean 7.12) underwent measurements annually. AL was measured using the Lenstar; height with the children standing, without shoes; and refraction using subjective refraction without cycloplegia. Participants were divided according to the refractive status: persistent emmetropia, persistent myopia, and newly developed myopia. The measurement time points of the persistent emmetropia and persistent myopia groups were marked as T1, T2, T3, T4, and T5. The time of myopia onset in the newly developed myopia group was marked as t 0; the preceding time points were marked as t -1, t -2, and so on, and the succeeding as t 1, t 2, and so on. The association between increase in AL and height was analyzed using simple correlation analysis. RESULTS: The mean changes in AL, height, and refraction were 1.39 mm, 23.60 cm, and -1.69 D, respectively, over 5 years in all children. The increase in AL and height were positively correlated for T1~T2, T1~T3, T1~T4, and T1~T5 (r = 0.262, P < 0.001; r = 0.108, P = 0.034; r = 0.165, P = 0.001; r = 0.174, P = 0.001, respectively). The changes in AL and height in the newly developed myopia group were significantly correlated (r = 0.289, P = 0.009) after myopia onset (t 0~t 2). CONCLUSION: The increase in AL and height were positively correlated, especially in the newly developed myopia group after myopia onset. Thus, when children grow quickly, AL elongation should be monitored.

MXene (Ti3C2) Based Pesticide Delivery System for Sustained Release and Enhanced Pest Control.

A multifunctional nanomaterials based pesticide delivery system provides a powerful strategy for the efficient utilization of pesticides. We present here the application of a 2D MXene (Ti3C2) nanomaterial for pesticide delivery and plant protection. Avermectin (AV), a hydrophobic and unstable insecticide, was chosen as the model pesticide. In our study, AV@Ti3C2 was formed by fast adsorption of AV on Ti3C2, with a maximum loading capacity of 81.44%. Compared with hydrophobic AV, AV@Ti3C2 exhibited significantly improved water solubility, which is beneficial for ensuring the bioactivity of pesticide. The AV@Ti3C2 nanoformulation showed pH responsive slow-release behavior, overcoming the burst-release of conventional AV formulations. Besides, AV@Ti3C2 possessed excellent photostability under UV irradiation, which prolonged the persistent period of AV. Therefore, AV@Ti3C2 performed sustaining and enhanced antipest activity, according to the bioactivity assay. Furthermore, AV@Ti3C2 showed satisfactory biosafety, with no negative effect to the germination and growth of maize. Our current research provides a potential candidate, AV@Ti3C2, for pest control, and also broadens the application of 2D MXene materials in plant protection and sustainable agriculture.

Can Clinical Measures of Postoperative Binocular Function Predict the Long-Term Stability of Postoperative Alignment in Intermittent Exotropia?

PURPOSE: To evaluate whether clinical measures of postoperative binocular functions could predict the long-term stability of postoperative ocular alignment in children with intermittent exotropia. METHODS: A retrospective study was performed in thirty-nine children (median: 7 years) who have been surgically treated from intermittent exotropia without overcorrection (less than 10 prism diopters [pd] of exodeviation at 1 month postoperatively). Angles of deviation and binocular functions were measured preoperatively and at 1 month, 6 months, and the final follow-up visit (≥24 months) postoperatively. We examined the relationships between postoperative drift (change of ocular alignment) and binocular functions (sensory fusion, fusional convergence amplitude, and stereoacuity). RESULTS: The surgical success rate (esophoria/tropia ≤5 pd to exophoria/tropia ≤10 pd) dropped to 76.9% at 6 months after surgery and to 53.8% at individuals' last visit (mean: 37 months). The mean exodrift was 7.7 ± 9.2 pd from the postoperative month 1 to the final visit (p < 0.001) on distance fixation. Distance stereoacuity, central fusion, and fusional convergence amplitude significantly improved following surgery (p < 0.05). However, no significant correlation was found between their binocular functions measured at the beginning of each follow-up period and the postoperative drift (all p > 0.13). CONCLUSION: Our findings suggest that the clinical measures of sensory fusion, fusional convergence amplitude, and stereoacuity cannot serve as a robust predictor for the long-term stability of postoperative ocular alignment in patients who underwent successful surgery without overcorrection at 1 month postoperatively.

Liver kinase B1 correlates with prognosis and epithelial-mesenchymal transition of resectable early stage non-small cell lung cancer.

BACKGROUND: Recent evidences support that low expression of liver kinase B1 (LKB1) triggers epithelial-mesenchymal transition (EMT) through induction of Zinc finger E-box binding homeobox 1 (ZEB1) expression, which downregulates E-cadherin in human lung cancer cell lines. However, the clinicopathological significance of LKB1, EMT, salt-inducible kinase 1 (SIK1), ZEB1 and their relationship in early stage non-small cell lung cancer (ES-NSCLC) patients remain to be determined. In this study, the correlation among expression of LKB1, risk of distant metastasis, prognostic significance, and EMT in ES-NSCLC after surgery was investigated by immunohistochemistry. METHODS: Case notes and pathology records of 103 patients with ES-NSCLC were retrospectively analyzed. Immunohistochemical staining was employed to detect LKB1, EMT biomarkers (E-cadherin and vimentin), SIK1 and ZEB1 expression in ES-NSCLC tissues. RESULTS: LKB1 expression is associated with distant metastasis after treatment (P=0.017). LKB1-high expression group has better overall survival (OS) (P=0.000) and disease-free survival (DFS) (P=0.000). LKB1 expression is correlated with E-cadherin (r=0.231, P=0.019), vimentin (r=-0.225, P=0.022), SIK1 (r=0.218, P=0.027) and ZEB1 (r=-0.242, P=0.014). CONCLUSIONS: Our findings suggest that LKB1-high expression is possibly associated with favourable prognosis and LKB1 expression is correlated with EMT and expression of SIK1 and ZEB1.

Discovery of N-(2-Aminophenyl)-4-(bis(2-chloroethyl)amino)Benzamide as a Potent Histone Deacetylase Inhibitor.

Inhibition of histone deacetylases (HDACs) has been an important emerging therapy for the treatment of multiple cancers. However, the application of HDAC inhibitors is restricted by the limited potency against solid tumors. In order to discover novel HDAC inhibitors with potent antitumor activities, nitrogen mustard group was introduced to the structure of CI994. The derived molecule N-(2-aminophenyl)-4-(bis(2-chloroethyl)amino)benzamide (NA) exhibited enzyme inhibitory pattern of class I selectivity with IC50 values of 95.2, 260.7, and 255.7 nM against HDAC1, HDAC2, and HDAC3, respectively. In the antiproliferative assay, NA exhibited 10.3-fold (2.66 µM) and 11.3-fold (1.73 µM) higher potency than did suberoylanilide hydroxamic acid (SAHA) (27.3 and 19.5 µM) in inhibition of A2780 and HepG2 cell growth, respectively. Further HepG2 cell-based cell cycle and apoptosis studies revealed that induction of the G2/M phase arrest and cell apoptosis contributes to the antitumor effects of NA. It is suggested that NA could be utilized as a lead compound in the development of bifunctional HDAC inhibitors for the treatment of solid tumors.

Regulation of BTG3 by microRNA-20b-5p in non-small cell lung cancer.

The present study aimed to evaluate microRNA- 20b-5p (miR-20b-5p) expression in non-small cell lung cancer (NSCLC), and investigate the effects of miR-20b-5p expression on NSCLC cell proliferation and migration. Reverse transcription-quantitative polymerase chain reaction was performed to measure the expression level of miR-20b-5p in NSCLC tissues and cell lines. Cell Counting Kit-8 and wound healing assays were used to measure cell proliferation and migration. A dual-luciferase reporter assay was performed to validate B-cell translocation gene 3 (BTG3) as a target of miR-20b-5p. It was identified that the expression level of miR-20b-5p is elevated in NSCLC tissues and cell lines. miR-20b-5p overexpression was revealed to promote NSCLC cell proliferation and migration. Furthermore, BTG3 was identified as a direct target of miR-20b-5p, and BTG3 overexpression reversed a miR-20b-5p mimic-induced increase in cell proliferation and migration. In summary, the present study revealed that miR-20b-5p promotes NSCLC cell proliferation and migration by targeting BTG3, which may assist with the development of a novel therapeutic target for the treatment of NSCLC.

Synthesis and Anticancer Activity Evaluation of Novel Phenanthridine Derivatives.

Based on the structure of sanguinarine, fourteen phenanthridine derivatives were designed and synthesized in the current study. The cytotoxic activities of synthesized compounds were evaluated against five human cancer cell lines (MCF-7, PC3, Hela, A549, and HepG2 cell lines) via MTT assay. Among all the compounds tested, molecule 8a exhibited significant cytotoxic activity against MCF-7 cells with a IC50 value of 0.28 µM. A following up enzymatic assay indicated that compound 8a could inhibit the activity of DNA topoisomerase I/II. Further mechanistic studies performed in the MCF-7 cell line revealed that compound 8a could arrest cell cycle in S phase and induce cell apoptosis via downregulation of Bcl-2 and upregulation of Bax. Collectively, a potent DNA topoisomerase inhibitor (8a) was discovered, which exhibited potential as a candidate chemotherapeutic agent for the management of tumors in the present study.

Intrabeam Radiation Inhibits Proliferation, Migration, and Invasiveness and Promotes Apoptosis of MCF-7 Breast Cancer Cells.

Intraoperative radiotherapy differs from the more commonly used external beam radiation with respect to fractionation, radiation energy, dose rate, and target volume, which may influence the irradiated cells in a complex manner. However, experimental studies of intraoperative radiotherapy are limited. Intrabeam is a frequently used intraoperative radiotherapy device; we evaluated its effects on the proliferation, apoptosis, migration, and invasion of MCF-7 human breast cancer cells. We performed colony formation assays for cells irradiated with single radiation doses of 0 to 16 Gy. Other cells were irradiated with single radiation doses of 0 to 6 Gy and then continued to be cultured. We measured cell-cycle distributions and apoptosis rates 24 hours later, using flow cytometry, and performed wound-healing assays, Transwell tests, and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling staining 4 weeks later. Colony formation assays showed no positive colonies from cells irradiated with doses of ≥6 Gy. In flow cytometry, the experimental groups had higher late-apoptosis/necrosis rates ( P < .01) and higher percentages of cells arrested in G1 phase ( P < .01). Experimental groups also had much lower scratch-repair rates in the wound healing assay ( P < .001) and higher apoptosis rates in the terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling assay ( P < .05). In Transwell tests, the 4 Gy and 6 Gy groups had fewer invading cells than the control group ( P < .05). Single-dose irradiation of 6 Gy with the Intrabeam device can effectively inhibit proliferation, migration, and invasiveness and promote apoptosis in MCF-7 cells with long-lasting effects.

Oncologic outcomes and radiation safety of nipple-sparing mastectomy with intraoperative radiotherapy for breast cancer.

BACKGROUND: Nipple-sparing mastectomy combined with breast reconstruction helps to optimize the contour of the breast after mastectomy. However, the indications for nipple-sparing mastectomy are still controversial. Local radiation to the nipple-areola complex may play some roles in improving the oncological safety of this procedure. METHODS: From January 2014 to December 2017, 41 consecutive patients who underwent nipple-sparing mastectomy combined with Intrabeam intraoperative radiotherapy to the nipple-areola complex flap and breast reconstruction were enrolled in this prospective study. The prescribed radiation dose at the surface of the spherical applicator was 16 Gy. RESULTS: In eight cases, carcinomas were in the central portion of the breast. Partial necrosis of the nipple-areola complex occurred in three cases. Over 90% of patients reported "no or poor sensation" of the nipple-areola complex postoperatively. With a median follow-up time of 26 months, no recurrences or metastases were identified; however, breast-cancer mortality occurred in one patient. Pathologic evaluation of paraffin-embedded sections showed ductal carcinoma in situ in the remaining tissues deep to the nipple-areola complex flap in two patients. Although no further treatment was administered to the nipple-areola complexes postoperatively, no recurrences or metastases were identified 20 months and 24 months later, respectively. Optical microscopy and transmission electron microscopy revealed changes in some normal tissues immediately after Intrabeam intraoperative radiotherapy. Karyopyknosis were observed in gland tissues, and the collagenous fibers became sparse and arranged chaotically. As assessed by thermoluminescence, radiation doses at different sites in the nipple-areola complex flap varied considerably and were about 10 Gy at the areola surface. No Intrabeam intraoperative radiotherapy-related acute or chronic radiation injuries of the lung, heart or bone marrow were identified. CONCLUSIONS: Our findings indicate that Intrabeam intraoperative radiotherapy during nipple-sparing mastectomy combined with breast reconstruction is safe and feasible. TRIAL REGISTRATION: The current study was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University (registering order 201750). All participants gave their written informed consent.