Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 433
Filtrar
1.
Cells ; 10(4)2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33800535

RESUMO

Regenerative medicine in ophthalmology that uses induced pluripotent stem cells (iPS) cells has been described, but those studies used iPS cells derived from fibroblasts. Here, we generated iPS cells derived from iris cells that develop from the same inner layer of the optic cup as the retina, to regenerate retinal nerves. We first identified cells positive for p75NTR, a marker of retinal tissue stem and progenitor cells, in human iris tissue. We then reprogrammed the cultured p75NTR-positive iris tissue stem/progenitor (H-iris stem/progenitor) cells to create iris-derived iPS (H-iris iPS) cells for the first time. These cells were positive for iPS cell markers and showed pluripotency to differentiate into three germ layers. When H-iris iPS cells were pre-differentiated into neural stem/progenitor cells, not all cells became positive for neural stem/progenitor and nerve cell markers. When these cells were pre-differentiated into neural stem/progenitor cells, sorted with p75NTR, and used as a medium for differentiating into retinal nerve cells, the cells differentiated into Recoverin-positive cells with electrophysiological functions. In a different medium, H-iris iPS cells differentiated into retinal ganglion cell marker-positive cells with electrophysiological functions. This is the first demonstration of H-iris iPS cells differentiating into retinal neurons that function physiologically as neurons.

2.
Mech Ageing Dev ; 196: 111492, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33862037

RESUMO

Tropomyosin (Tpm) 1 and 2 are important in the epithelial mesenchymal transition of lens epithelial cells; however, the effect of Tpm1 depletion during aging remains obscure. We analyzed the age-related changes in the crystalline lens of Tpm1- conditional knockout mice (Tpm1-CKO). Floxed alleles of Tpm1 were conditionally deleted in the lens, using Pax6-cre transgenic mice. Lenses of embryonic day (ED) 14, postnatal 1-, 11-, and 48-week-old Tpm1-CKO and wild type mice were dissected to prepare paraffin sections, which subsequently underwent histological and immunohistochemical analysis. Tpm1 and α smooth muscle actin (αSMA) mRNA expression were assessed using RT-PCR. The homozygous Tpm1-CKO (Tpm1-/-) lenses displayed a dramatic reduction in Tpm1 transcript, with no change to αSMA mRNA expression. Tpm1-/- mice had small lenses with disorganized, vesiculated fiber cells, and loss of epithelial cells. The lenses of Tpm1-/- mice had abnormal and disordered lens fiber cells with cortical and peri-nuclear liquefaction. Expression of filamentous-actin was reduced in the equator region of lenses derived from ED14, 1-, 11-, and 48-week-old Tpm1-/- mice. Therefore, Tpm1 plays an integral role in mediating the integrity and fate of lens fiber differentiation and lens homeostasis during aging. Age-related Tpm1 dysregulation or deficiency may induce cataract formation.

3.
Cancers (Basel) ; 13(5)2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33668270

RESUMO

We performed a systematic review and meta-analysis to assess the prognostic value of prostate-specific antigen (PSA) persistence 4-8 weeks after radical prostatectomy (RP) in patients with prostate cancer, using studies from Medline, Scopus, and Cochrane Library, on 10 October 2020. Studies were eligible if they compared patients with postoperative PSA persistence 4-8 weeks after RP to those without such persistence to assess the value of PSA persistence in prognosticating biochemical recurrence (BCR), disease recurrence, cancer-specific mortality (CSM), and overall mortality (OM) by multivariable analysis. Our review and analysis included nine studies published between 2008 and 2019 with 14,455 patients. Of those studies, 12.0% showed postoperative PSA persistence. PSA persistence was associated with BCR (HR: 4.44, 95% CI: 2.84-6.93), disease recurrence (HR: 3.43, 95% CI: 1.62-7.25), and CSM (HR: 2.32, 95% CI: 1.83-2.95). We omitted meta-analysis on the association of PSA persistence with OM due to an insufficient number of studies. PSA persistence was associated with disease recurrence in a sub-group of patients with pathological nodal involvement (HR: 5.90, 95% CI: 3.76-9.24). Understanding detection of PSA persistence at 4-8 weeks after RP might be useful for patient counseling, follow-up scheduling, and clinical decision-making regarding adjuvant therapies.

4.
Med Mol Morphol ; 2021 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-33458799

RESUMO

The incidence rate of post-cataract surgery posterior capsule opacification (PCO) and lens turbidity is about 20% in 5 years. Soemmering's ring, which is a type of PCO also called a regenerated lens with similar tissue structure to that of a human lens, is an important proxy for elucidating the mechanism of lens regeneration and maintenance of transparency. The authors created new human immortalized crystalline lens epithelial cells (iHLEC-NY1s) with excellent differentiation potential, and as a result of culturing the cells by static and rotation-floating methods, succeeded in producing a three-dimensional cell structure model (3D-iHLEC-NY1s) which is similar to Soemmering's ring in tissue structure and expression characteristics of αA-crystalline, ßB2-crystalline, vimentin proteins. 3D-iHLEC-NY1s is expected to be a proxy in vitro experimental model of Soemmering's ring to enable evaluation of drug effects on suppression of cell aggregate formation and transparency. By further improving the culture conditions, we aim to control the cell sequence and elucidate the mechanism underlying the maintenance of lens transparency.

5.
J Ocul Pharmacol Ther ; 37(2): 97-103, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33439755

RESUMO

Purpose: We sought to evaluate the effect of antiglaucoma ophthalmic solutions on the cornea with a corneal resistance device (CRD), and to compare the results with those by fluorescein staining. Methods: In 6 rabbit groups (n = 7 each), right eyes were administered latanoprost ophthalmic solution containing 0.02% benzalkonium chloride (BAK); dorzolamide/timolol (1%/0.5%) containing 0.005% BAK; dorzolamide/timolol without BAK; dorzolamide/timolol+latanoprost with 0.02% BAK; 0.005% BAK; or 0.02% BAK to the conjunctival sac 3 × at 15-min intervals. Left (control) eyes were administered saline. Baseline and post-treatment corneal resistance (CR) were measured. The CR ratio = CR before versus after treatment. We evaluated superficial punctate keratitis by fluorescein staining using area and density (AD) grades. Results: In the dorzolamide/timolol-without BAK group, there were no significant difference in the CR ratio between the control and treatment eyes at any time point. In the 0.005%-BAK group at 30 min and the other 4 groups at all time points, the CR ratio differed significantly between the control and treatment eyes (P < 0.05). AD grades were 0 in all control eyes and the dorzolamide/timolol-without BAK and 0.005% BAK treatment eyes. Conclusions: Nonpreservative ophthalmic solutions (and those with low BAK concentrations) do not significantly affect corneal electrical resistance. Eye drop ingredients other than BAK may be involved in altering corneal electrical resistance. CRDs may detect corneal epithelium changes not revealed by fluorescein staining.

6.
Cells ; 9(12)2020 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-33322631

RESUMO

The prevalence of nuclear cataracts was observed to be significantly higher among residents of tropical and subtropical regions compared to those of temperate and subarctic regions. We hypothesized that elevated environmental temperatures may pose a risk of nuclear cataract development. The results of our in silico simulation revealed that in temperate and tropical regions, the human lens temperature ranges from 35.0 °C to 37.5 °C depending on the environmental temperature. The medium temperature changes during the replacement regularly in the cell culture experiment were carefully monitored using a sensor connected to a thermometer and showed a decrease of 1.9 °C, 3.0 °C, 1.7 °C, and 0.1 °C, after 5 min when setting the temperature of the heat plate device at 35.0 °C, 37.5 °C, 40.0 °C, and 42.5 °C, respectively. In the newly created immortalized human lens epithelial cell line clone NY2 (iHLEC-NY2), the amounts of RNA synthesis of αA crystallin, protein expression, and amyloid ß (Aß)1-40 secreted into the medium were increased at the culture temperature of 37.5 °C compared to 35.0 °C. In short-term culture experiments, the secretion of Aß1-40 observed in cataracts was increased at 37.5 °C compared to 35.0 °C, suggesting that the long-term exposure to a high-temperature environment may increase the risk of cataracts.

7.
Cancer Biol Ther ; 21(12): 1128-1135, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33190594

RESUMO

Cervical cancer is the fourth-most prevalent malignancy in women. For advanced cervical cancer, radiotherapy is a major treatment. Micro RNAs (miRNAs) are small, noncoding RNAs that negatively regulate the target gene expression posttranscriptionally. miR-22 is frequently downregulated in various cancers including cervical cancer, and is associated with a poor prognosis in cervical cancer. Exosomes are small endosomally secreted vesicles that carry components such as proteins, messenger RNA (mRNA), DNA and miRNA. We investigated whether or not exosomes can efficiently deliver miR-22 to recipient cervical cancer cells and affect the gene expression in the cells, as well as assessed the role of exosomal miR-22 in radiosensitivity. Exosomes containing high levels of miR-22 were extracted by ultracentrifugation and then characterized by Western blotting, a nanoparticle tracking analysis and electron microscopy. The high presence of miR-22 in the exosome was confirmed by real-time polymerase chain reaction. After the administration of the collected exosomal miR-22 to SKG-II and C4-I cervical cancer cells, the level of miR-22 in the cells was significantly increased, indicating the absorption of the exosomal miR-22. When miR-22 encapsulated in exosomes was administered to the SKG-II cells, the level of c-Myc binding protein (MYCBP) and human telomerase reverse transcriptase (hTERT) was significantly decreased in correlation with increased radiosensitivity determined by a clonogenic assay. Taken together, these results suggest that the administration of exosomal miR-22 may be a novel drug delivery system for cervical cancer radiotherapy.

8.
Biomed Res Int ; 2020: 7319590, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204712

RESUMO

The Shumiya cataract rat (SCR) is a model for hereditary cataract. Two-thirds of these rats develop lens opacity within 10-11 weeks. Onset of cataract is attributed to the synergetic effect of lanosterol synthase (Lss) and farnesyl-diphosphate farnesyltransferase 1 (Fdft1) mutant alleles that lead to cholesterol deficiency in the lenses, which in turn adversely affects lens biology including the growth and differentiation of lens epithelial cells (LECs). Nevertheless, the molecular events and changes in gene expression associated with the onset of lens opacity in SCR are poorly understood. In the present study, a microarray-based approach was employed to analyze comparative gene expression changes in LECs isolated from the precataractous and cataractous stages of lenses of 5-week-old SCRs. The changes in gene expression observed in microarray results in the LECs were further validated using real-time reverse transcribed quantitative PCR (RT-qPCR) in 5-, 8-, and 10-week-old SCRs. A mild posterior and cortical opacity was observed in 5-week-old rats. Expressions of approximately 100 genes, including the major intrinsic protein of the lens fiber (Mip and Aquaporin 0), deoxyribonuclease II beta (Dnase2B), heat shock protein B1 (HspB1), and crystallin γ (γCry) B, C, and F, were found to be significantly downregulated (0.07-0.5-fold) in rat LECs derived from cataract lenses compared to that in noncataractous lenses (control). Thus, our study was aimed at identifying the gene expression patterns during cataract formation in SCRs, which may be responsible for cataractogenesis in SCR. We proposed that cataracts in SCR are associated with reduced expression of these lens genes that have been reported to be related with lens fiber differentiation. Our findings may have wider implications in understanding the effect of cholesterol deficiency and the role of cholesterol-lowering therapeutics on cataractogenesis.

9.
Comput Biol Med ; 126: 104009, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33011577

RESUMO

Recent epidemiological studies have hypothesized that the prevalence of cortical cataracts is closely related to ultraviolet radiation. However, the prevalence of nuclear cataracts is higher in elderly people in tropical areas than in temperate areas. The dominant factors inducing nuclear cataracts have been widely debated. In this study, the temperature increase in the lens due to exposure to ambient conditions was computationally quantified in subjects of 50-60 years of age in tropical and temperate areas, accounting for differences in thermoregulation. A thermoregulatory response model was extended to consider elderly people in tropical areas. The time course of lens temperature for different weather conditions in five cities in Asia was computed. The temperature was higher around the mid and posterior part of the lens, which coincides with the position of the nuclear cataract. The duration of higher temperatures in the lens varied, although the daily maximum temperatures were comparable. A strong correlation (adjusted R2 > 0.85) was observed between the prevalence of nuclear cataract and the computed cumulative thermal dose in the lens. We propose the use of a cumulative thermal dose to assess the prevalence of nuclear cataracts. Cumulative wet-bulb globe temperature, a new metric computed from weather data, would be useful for practical assessment in different cities.

11.
Urol Oncol ; 38(12): 938.e1-938.e7, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33036899

RESUMO

PURPOSE: To evaluate the clinical trifecta of percutaneous cryoablation (PCA) vs. laparoscopic partial nephrectomy (LPN) for cT1 renal tumors. PATIENTS AND METHODS: We retrospectively analyzed the records of patients who had undergone 2 types of nephron sparing surgeries (NSS) PCA or LPN for cT1 renal tumors between November 2011 and December 2019. The cohorts were matched by one-to-one propensity scores based on patient demographics, renal function, and tumor complexity. Perioperative and oncological outcomes and preservation of renal function following surgery were compared. RESULTS: After matching, a total of 180 patients who had undergone NSS for de novo renal tumors were evaluable: 90 for PCA and 90 for LPN. No statistically significant differences were noted among the measured baseline characteristics in the propensity score-matched cohorts. Overall perioperative complication rates were 5.5% in the PCA and 11.1% in the LPN groups (P = 0.28). The rate of eGFR preservation 1 to 3 months after surgery was significantly higher for PCA than for LPN (92.8 ± 11.5% vs. 88.5 ± 14.6%, P = 0.03). Median follow-up was 33 months for PCA and 18 months for LPN (P < 0.001). Three residual and 4 recurrent tumors were later diagnosed in the PCA group and 1 recurrent tumor in the LPN group. The 5-year local recurrence-free survival was lower for PCA than LPN (90.2% vs. 98.5%, P = 0.36). The 5-year metastasis-free survival rate was similar in both groups (98.4% vs. 100%, P = 0.38). The 5-year overall and cancer-specific survival rates were comparable in both groups (91.7% vs. 98.9%, P = 0.53, and 95% vs. 100%, P = 0.55, respectively). CONCLUSIONS: Clinical T1 RCC patients are better treated with LPN if technically possible. Though PCA had a higher local recurrence rate, medium-term local control was not inferior to LPN. Additionally, PCA patients tended to retain renal function without severe complications. PCA appears to be a reasonable option for patients with high comorbidity at presentation.

12.
World J Urol ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33079252

RESUMO

PURPOSE: To evaluate the health-related quality of life (HRQoL) of Japanese men on active surveillance (AS) in the Prostate cancer Research International Active Surveillance study in Japan (PRIAS-JAPAN). METHODS: Participants were included in the PRIAS-JAPAN HRQoL study between January 2010 and March 2016. Their general HRQoL was assessed using a validated Japanese version of the Short-Form 8 Health Survey (SF-8) at enrolment and annually thereafter until discontinuation of AS. The SF-8 mental component summary (MCS) and physical component summary (PCS) of men on AS were compared with scores of the general population (norm-based score [NBS]: 50) and MCS and PCS scores for men following AS were analysed over time. We tested whether MCS and PCS scores over time explained discontinuation of AS. RESULTS: Five hundred and twenty-five patients enrolled, and the median age at baseline was 68 years. At enrolment and after 1-, 2-, and 3-year follow-ups, the PCS and MCS scores were significantly higher than the NBS of the general Japanese population except for the median PCS at 3 years. We found that age at diagnosis and time on AS negatively affected the PCS score of men on AS, while every additional year on AS led to a 0.27 point increase in MCS scores. Neither PCS nor MCS were predictors for discontinuation of AS. CONCLUSION: Japanese men following an AS strategy for 3 years reported better HRQoL compared with the general population, indicating that monitoring Japanese low-risk prostate cancer patients can be an effective treatment strategy. STUDY REGISTRATION: Clinical trial registry-UMIN (University Hospital Medical Information Network); UMIN000002874 (2009/12/11).

14.
Exp Eye Res ; 199: 108194, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32822701

RESUMO

A sight threatening, pterygium is a common ocular surface disorders identified by fibrovascular growth of the cornea and induced by variety of stress factors, like ultraviolet (UV) exposure. However, the genes involved in the etiopathogenesis of this disease is not well studied. Herein, we identified the gene expression pattern of pterygium and examined the expression of pterygium-related genes in UV-B-induced human primary cultured corneal epithelial cells (HCEpCs), telomerase immortalized human corneal epithelial (hTCEpi), primary conjunctival fibroblast (HConFs) and primary pterygium fibroblast cells (HPFCs). A careful analysis revealed that the expression of 10 genes was significantly modulated (by > 10-fold). Keratin 24 (KRT24) and matrix metalloproteinase 9 (MMP-9) were dramatically upregulated by 49.446- and 24.214-fold, respectively. Intriguingly, UV-B exposure (50 J/m2) induced the upregulation of the expressions of MMP-9 in corneal epithelial cells such as HCEpCs and hTCEpi. Furthermore, UV-B exposure (100 and/or 200 J/m2) induced the upregulation of the expressions of MMP-9 in fibroblast such as HConFs and HPFCs. The exposure of HCEpCs to 100 and 200 J/m2 UV-B induced significant expressions of KRT24 mRNA. Nevertheless, no expression of KRT24 mRNA was detected in HConFs and HPFCs. The findings provide evidence that the progression of pterygium may involve the modulation of extracellular matrix-related genes and vasculature development and the up-regulation of KRT24 and MMP-9 by UV stress. UV radiation may promote the modulation of these pterygium-related genes and induce the initiation and progression of human pterygium.

15.
Curr Opin Cell Biol ; 67: 1-8, 2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32763500

RESUMO

Cell competition is a short-range intercellular communication, in which cells compare their fitness with that of their neighbors and eliminate the cells with relatively lower fitness. It is considered important for the formation and maintenance of healthy tissues; however, its exact role during development, especially in mammals, has been obscure. Recent studies in mouse embryonic epiblast and skin tissues revealed that cell differentiation in early embryos and stem cell proliferation tends to produce suboptimal cells, especially during early developmental stages. Cell competition occurs at multiple stages and via multiple mechanisms during development to ensure elimination of such low-quality cells. Thus, quality control via cell competition supports correct development by overcoming the heterogeneity produced during cell differentiation and stem cell proliferation.

16.
Int J Clin Oncol ; 25(12): 2107-2114, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32770439

RESUMO

BACKGROUND: Patients with favorable-risk prostate cancer on active surveillance (AS) are strictly followed for safer execution. Repeat protocol biopsy is essential for evaluating cancer aggressiveness. However, the acceptance rate of repeat biopsy is not high enough because of the burdens of biopsy. We assessed the impact of complications after the initial biopsy on repeat protocol biopsy at 1 year using data from the Prostate Cancer Research International: Active Surveillance (PRIAS)-JAPAN study. METHODS: We performed a retrospective analysis using a prospective cohort in the PRIAS-JAPAN study. Patients with favorable-risk prostate cancer (n = 856) who consented to participate in the PRIAS-JAPAN study from 2010 to 2018 were enrolled. Follow-up evaluations included regular prostate-specific antigen, digital rectal examination and biopsy. Rates of complications after biopsies and repeat protocol biopsy non-acceptance rate at 1 year were reported. Logistic regression analysis explored the association between the complications after the initial biopsy and repeat protocol biopsy non-acceptance. RESULTS: Altogether, 759 patients (88.7%) actually proceeded to protocol at 1 year. Repeat protocol biopsy non-acceptance rate at 1 year was 14.9%. Regarding complications after the initial biopsy, hematuria (p = 0.028) and pain (p < 0.001) rates were significantly higher in the repeat biopsy non-acceptance group, but infection (p = 0.056) and hematospermia (p = 0.337) rates were not different. On multivariate logistic regression analysis, pain was a significant predictor for repeat protocol biopsy non-acceptance (odds ratio 4.68, 95% confidence interval 1.864-11.75; p = 0.001). CONCLUSIONS: Pain at the initial biopsy negatively impacts patients' compliance with further protocol biopsies during AS.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32733870

RESUMO

We previously developed ophthalmic formulations containing tranilast nanopartaicles (ophthalmic TL-NPs formulations), and found them to show high uptake into ocular tissues. In this study, we aimed to design an in situ gel incorporating TL-NPs with 0.5-3% methylcellulose (MC, type SM-4) to ensure long residence time of the drug at the ocular surface. The ophthalmic TL-NPs formulations were prepared by the bead mill method, which yielded a mean particle size of ~93 nm with or without MC (0.5-3%). Although the dispersibility of TL particles in ophthalmic formulations increased with the MC content, the diffusion behavior of TL particles in the dispersion medium decreased with MC content. In an in vivo study using rats, the TL content in the lacrimal fluid was enhanced with MC content in the ophthalmic TL-NPs formulations, and the optimum amount of MC (0.5-1.5%) enhanced the TL content in the cornea and conjunctiva, and an anti-inflammatory effect of TL in rats instilled with ophthalmic TL-NPs formulations was observed. On the other hand, excessive MC (3%) prevented the corneal uptake of TL-NPs after instillation, and the anti-inflammation effect of TL was lower than that of ophthalmic TL-NPs formulations with optimum MC (0.5-1.5%). In conclusion, we found that gel formulations of TL-NPs with 0.5 and 1.5% MC provided a prolonged pre-corneal and pre-conjunctival contact time of TL, and resulted in higher TL contents in the cornea and conjunctiva following instillation in comparison with TL-NPs with or without 3% MC. This is probably due to the balance between the higher residence time and faster diffusion of TL-NPs on the ocular surface. These findings provide significant information that can be used to design further studies aimed at developing ophthalmic nanomedicines.

18.
Pharmaceutics ; 12(7)2020 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-32635523

RESUMO

We attempted to prepare ophthalmic in situ gel formulations containing lanosterol (Lan) nanoparticles (LA-NPs/ISG) and investigated the characteristics, delivery pathway into the lens, and anti-cataract effects of LA-NPs/ISG using SCR-N (rats with slight lens structure collapse) and SCR-C (rats with a combination of remarkable lens structure collapse and opacification). LA-NPs/ISG was prepared by bead milling of the dispersions containing 0.5% Lan powder, 5% 2-hydroxypropyl-ß-cyclodextrin, 0.5% methylcellulose, 0.005% benzalkonium chloride, and 0.5% mannitol. The particle size distribution of Lan was 60-250 nm. The LA-NPs/ISG was gelled at 37 °C, and the LA-NPs/ISG was taken into the cornea by energy-dependent endocytosis and then released to the intraocular side. In addition, the Lan contents in the lenses of both SCR-N and SCR-C were increased by the repetitive instillation of LA-NPs/ISG (twice per day). The space and structure collapse in the lens of SCR-N with aging was attenuated by the instillation of LA-NPs/ISG. Moreover, the repetitive instillation of LA-NPs/ISG attenuated the changes in cataract-related factors (the enhancement of nitric oxide levels, calpain activity, lipid peroxidation levels, Ca2+ contents, and the decrease of Ca2+-ATPase activity) in the lenses of SCR-C, and the repetitive instillation of LA-NPs/ISG delayed the onset of opacification in the SCR-C. It is possible that the LA-NPs/ISG is useful in maintaining lens homeostasis.

19.
Biomed Res Int ; 2020: 9204620, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32509875

RESUMO

Age-related cataract (ARC) is the major cause of blindness worldwide. The most significant factors are the maximal exposure of the eye lens to environmental stressors, including oxidative and glycative load. The administration of antioxidant and antiglycative supplements may reduce the risk of cataract progression. In this study, the effects of lutein (LU) and water chestnut (Trapa bispinosa Roxb.) extract (TBE) on cataracts and the expression of antioxidant-related genes were assessed in Shumiya cataract rats (SCRs). LU+TBE or castor oil (COil) as a control was administered to 6- or 9-week-old cataractous SCRs and noncataractous SCRs via a feeding needle for 3 or 4 weeks. Five-week-old SCRs were provided ad libitum access to solid regular chow containing LU, TBE, LU+TBE, or the same chow without LU and/or TBE for 3 weeks. Lenses from all rats were then extracted and photographed. The right eyes of the rats were processed for histological observation, and the left eyes were used for total RNA extraction from lens epithelial cells (LEC). The mRNA levels of antioxidant proteins, peroxiredoxin 6, and catalase were examined using real-time quantitative polymerase chain reaction. Lens opacity appeared in all cataractous SCRs that began receiving LU+TBE at 9 weeks of age. However, compared to the COil group, lens opacity was decreased in the cataractous LU+TBE SCRs in all experiments. The mRNA expression levels of peroxiredoxin 6 and catalase in LECs of cataractous SCRs and cultured human LECs increased after the administration of LU+TBE. Collectively, our results highlight the anticataract and antioxidative effects of LT+TBE in SCRs. LT+TBE supplementation may, thus, be useful in delaying cataract progression.

20.
Int J Clin Oncol ; 25(9): 1695-1703, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32488548

RESUMO

BACKGROUND: In the present guidelines for the management of metastatic castration-resistant prostate cancer (mCRPC), it is unclear who benefits most from androgen receptor axis-targeted agents (ARATs) or docetaxel as the first-line treatment. METHODS: We conducted a retrospective study to explore new treatment-specific biomarkers in mCRPC. A total of 211 patients with mCRPC who received either ARAT or docetaxel as first-line treatment were included. Patients were compared for radiographic progression and prostate-specific antigen (PSA) progression. Multivariable Cox regression models were used to assess the association between pretreatment biomarkers and risk of events. The statistical interaction between biomarkers and clinical outcomes was also evaluated. RESULTS: Of all analyzed biomarkers, multivariable Cox regression models identified MPV [≤ median (9.7 fL)] as an independent prognostic factor of radiographic progression [hazard ratio (HR), 2.35; 95% confidence interval (CI), 1.15-4.80; P = 0.019] and PSA progression (HR, 1.96; 95% CI, 1.01-3.95; P = 0.048) in patients treated with ARAT, whereas such associations were not observed in those treated with docetaxel. Interaction analyses showed that those initially treated with docetaxel have lower risk of radiographic progression (HR, 0.33; 95% CI, 0.13-0.79; P = 0.014) and PSA progression (HR, 0.48; 95% CI, 0.23-0.98; P = 0.044) than ARAT when MPV was small. CONCLUSIONS: The present study identified pretreatment MPV as a significant treatment-specific prognostic factor of PSA and radiographic progression in patients with mCRPC who received first-line treatment. Furthermore, our results suggested that those with small MPV may better be treated initially with docetaxel than ARAT.


Assuntos
Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Androstenos/uso terapêutico , Biomarcadores Tumorais , Docetaxel/uso terapêutico , Eritrócitos/patologia , Humanos , Masculino , Volume Plaquetário Médio , Feniltioidantoína/análogos & derivados , Feniltioidantoína/uso terapêutico , Contagem de Plaquetas , Prognóstico , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias de Próstata Resistentes à Castração/patologia , Receptores Androgênicos , Estudos Retrospectivos , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...