Purpose Skin pigmentation disorders,such as vitiligo and melasma,are difficult to diagnose in the early stages,but abnor-mal tyrosinase levels and tyrosinase activity are potential indicators.Some resorufin-based fluo...Purpose Skin pigmentation disorders,such as vitiligo and melasma,are difficult to diagnose in the early stages,but abnor-mal tyrosinase levels and tyrosinase activity are potential indicators.Some resorufin-based fluorescence probes(RBFPs)have been designed to detect tyrosinase in tumors,but they have not been used in skin pigmentation disorders.In this study,one of these RBFPs(synthesized by resorufin salt coupled with 3-(bromomethyl)phenol)was evaluated comprehensively.Methods The RBFP was tested in different kinds of mouse and human skin cells,as well as in in vivo models,including zebrafish,guinea pigs,and Sprague-Dawley rats.In addition,small interfering RNAs(siRNAs),kojic acid,and 1-phenyl-2-thiourea(PTU)were used to inhibit tyrosinase levels or tyrosinase activity.Results This probe successfully detected tyrosinase and emitted red fluorescence in melanoma cells and melanocytes.Fluorescence was also observable in zebrafish and on the skin of guinea pigs when using the RBFP.In mouse and human cells,the RBFP showed good selectivity to tyrosinase.Moreover,in the case of decreased tyrosinase levels or activity caused by siRNAs,kojic acid,or PTU,the probe was sensitive to these changes.Further,the RBFP showed no toxic effects at concentrations of<20μmol/L,both in vitro and in vivo.Conclusions Our findings indicate the value and limitations of the RBFP in tyrosinase detection,but suggest the need for further improvement of fluorescent probes in the diagnosis of skin pigmentation disorders.展开更多
Beetles in the family Coccinellidae, commonly known as ladybugs, lady beetles, or ladybirds, are easily identifiable and popular beneficial insects. Current research aims to support conservation efforts of beneficial ...Beetles in the family Coccinellidae, commonly known as ladybugs, lady beetles, or ladybirds, are easily identifiable and popular beneficial insects. Current research aims to support conservation efforts of beneficial insects in agroecosystems by exploring genetic processes related to nutrition. As a part of this research, colonies of Coleomegilla maculata have been maintained in culture and inbred over many generations since 2009. One result of this inbreeding has been the discovery of novel morphological phenotypes unique to laboratory strains or present in wild populations at such low levels that they have not yet been described. One such phenotype is described here. The strain described here, ye (yellow elytra and eyes) was characterized with classical Mendelian breeding and digital image analysis. This phenotype differs from wild populations by possessing yellow pigment in the elytra and pale grey to white eyes. In contrast, wild populations of C. maculata possess pink or red pigmented elytra with black spots, and black eyes. C. maculata is not known to exhibit polymorphism in the field. Inheritance is autosomal and recessive. This species was not previously known to exhibit the dramatic variation of color described here. The strain is stable in the homozygous recessive form, and retains laboratory rearing characteristics similar to the wild type laboratory strain.展开更多
We report the case of a 10-year-old girl with congenital complete heterochromia iridis and segmental pigmentation disorder in its hyperpigmented form. We have found no publication that mentions the combination of thes...We report the case of a 10-year-old girl with congenital complete heterochromia iridis and segmental pigmentation disorder in its hyperpigmented form. We have found no publication that mentions the combination of these 2 disorders.展开更多
Pigmentation of the oral mucosa is relatively common and has a wide variety of etiologies. Although most pigmented lesions of the oral mucosa are associated with deposition of melanin and accidental displacement of a ...Pigmentation of the oral mucosa is relatively common and has a wide variety of etiologies. Although most pigmented lesions of the oral mucosa are associated with deposition of melanin and accidental displacement of a dental alloy, accurate differential diagnosis of a pigmented lesion is important, especially in the case of malignant melanoma. We report two cases of oral mucosal pigmentation associated with accidental displacement of a dental alloy in which malignant melanoma was suspected. Excisional biopsy was carried out in these cases with the incision line set at approximately 5 mm from the lesions. Histopathologically, brownish foreign substances were observed in the lamina propria. Metal quantitative analyses of the extracted specimens were carried out by electron probe microanalysis (EPMA). The metal components and the mass concentration revealed that the metals were derived from a dental casting silver alloy in Case 1 and from a gold-silver palladium alloy in Case 2. Although exogenous pigmentation originating from a dental alloy is not rare, differential diagnosis of oral pigmented lesions is sometimes very difficult. In such cases, histopathological examination may be necessary for the diagnosis to exclude melanocytic lesions and EPMA may be effective to identify the causative dental alloy.展开更多
Background: Most data on laser resurfacing have come from studies of people with Fitzpatrick skin types 1 - 3;however, the world’s population is comprised mostly of Fitzpatrick skin types 4 - 6, which are more suscep...Background: Most data on laser resurfacing have come from studies of people with Fitzpatrick skin types 1 - 3;however, the world’s population is comprised mostly of Fitzpatrick skin types 4 - 6, which are more susceptible to post-inflammatory hyperpigmentation (PIH). Objective: For the purpose of expanding the expertise of plastic surgeons treating patients with darker skin types, this study examined the incidence of PIH in Asians who underwent laser resurfacing, including a histologic arm on fractional ablative resurfacing. Methods & Materials: The clinical study included six subjects of Vietnamese origin who underwent single-depth fractionated CO2 laser resurfacing. The histologic study involved a seventh subject. The MiXto SX®laser with a new scanning handpiece was used, along with magnifying loupes to assess ablative depth after each of three laser passes performed. Photographs were taken at various postoperative intervals. Results: All six clinical subjects showed cosmetic improvement in skin texture and tone with no post-inflammatory hyperpigmentation. In the histologic study, H&E stained sections revealed uniform diathermy. Conclusion: It is possible to significantly reduce PIH in darker skinned subjects through use of a new scanning handpiece and a technique using loupes to assess the depth of ablative resurfacing. The histologic study confirms these findings.展开更多
A laboratory colony of Coleomegilla maculata (DeGeer), ye, selected for a pigmentation deficiency, was restored to near wild type cuticle coloration by adding crushed heads and wings of the red colored parental strain...A laboratory colony of Coleomegilla maculata (DeGeer), ye, selected for a pigmentation deficiency, was restored to near wild type cuticle coloration by adding crushed heads and wings of the red colored parental strain to the diet. While the wings and other colored portions of the cuticle re-gained the red color, the eyes of the pigmentation deficient insects were not changed from the pale mutant form. Plant derived carotenes lycopene and beta-carotene did not restore the mutant beetles to a visibly distinguishable red color. An additional pigmentation deficient mutant strain, gold, partially recovered red cuticle color when provided with diet containing pigmented insect particles. This work represents the first rescue of a color phenotype in a lady beetle.展开更多
The pigmentation in the liver of Chinese fire-bellied newt(Cynops orientalis) was described during two periods of the annual cycle(summer activity and winter hibernation). A large number of melanin granules were gathe...The pigmentation in the liver of Chinese fire-bellied newt(Cynops orientalis) was described during two periods of the annual cycle(summer activity and winter hibernation). A large number of melanin granules were gathered into clusters and distributed unevenly inside the pigment cells. Liver pigmentation(melanin content) was found unstable,varying during the annual cycle. During the hibernation period,pigmentation accumulation was shown to increase in the liver of the Chinese fire-bellied newt. Hepatocytes during the active period are approximately 14.64% larger than those in the hibernation period,while the nucleus is approximately 7.43% bigger during the active period when compared with that during the hibernation period. These findings indicate that variation in pigment distribution and hepatocyte morphology in Chinese fire-bellied newt liver may be an ecologically adaptive strategy to the adverse physiological conditions during hibernation.展开更多
A laboratory colony of <i>Coleomegilla maculata</i> (DeGeer), ye, selected for a pigmentation deficiency, was restored to near wild type cuticle coloration by adding crushed heads and wings of the red colo...A laboratory colony of <i>Coleomegilla maculata</i> (DeGeer), ye, selected for a pigmentation deficiency, was restored to near wild type cuticle coloration by adding crushed heads and wings of the red colored parental strain to the diet. While the wings and other colored portions of the cuticle re-gained the red color, the eyes of the pigmentation deficient insects were not changed from the pale mutant form. Plant derived carotenes lycopene and beta-carotene did not restore the mutant beetles to a visibly distinguishable red color. An additional pigmentation deficient mutant strain, gold, partially recovered red cuticle color when provided with diet containing pigmented insect particles. This work represents the first rescue of a color phenotype in a lady beetle.展开更多
Pod coloration is a domestication-related trait in soybean,with modern cultivars typically displaying brown or tan pods,while their wild relative,Glycine soja,possesses black pods.However,the factors regulating this c...Pod coloration is a domestication-related trait in soybean,with modern cultivars typically displaying brown or tan pods,while their wild relative,Glycine soja,possesses black pods.However,the factors regulating this color variation remain unknown.In this study,we cloned and characterized L1,the classical locus responsible for black pods in soybean.By using map-based cloning and genetic analyses,we identified the causal gene of L1 and revealed that it encodes a hydroxymethylglutaryl-coenzyme A(CoA)lyase-like(HMGL-like)domain protein.Biochemical assays showed that L1 functions as a eucomic acid synthase and facilitates the synthesis of eucomic acid and piscidic acid,both of which contribute to coloration of pods and seed coats in soybean.Interestingly,we found that L1 plants are more prone to pod shattering under light exposure than l1 null mutants because dark pigmentation increases photothermal efficiency.Hence,pleiotropic effects of L1 on pod color and shattering,as well as seed pigmentation,likely contributed to the preference forl1 alleles during soybean domestication and improvement.Collectively,our study provides new insights into the mechanism of pod coloration and identifies a new target for future de novo domestication oflegume crops.展开更多
Objective:The zinc finger,MIZ-type containing 1(ZMIZ1)gene has been identified as a possible susceptibility gene associated with vitiligo,therefore we conducted this study to investigate the role ofZMIZ1 in pigmentati...Objective:The zinc finger,MIZ-type containing 1(ZMIZ1)gene has been identified as a possible susceptibility gene associated with vitiligo,therefore we conducted this study to investigate the role ofZMIZ1 in pigmentation.Methods:We generate a zebrafish loss-of-function model using morpholino oligonucleotides(MOs),and two orthologs of humanZMIZ1 have been annotated(ZMIZ1a andZMIZ1b).The expression profiles of ZMIZ1a and ZMIZ1b and their effects on the pigmentation in zebrafish were evaluated by using whole-mount in situ hybridization and melanin quantification.Statistical analysis was performed using the unpaired Studentt-test or one-way analysis.Results:Investigation of the temporal and spatial expressions of these two transcripts suggested that the expressions ofZMIZ1a andZMIZ1b in the brain start to emerge in a ubiquitous fashion from 2 days post-fertilization onwards.After the successful design and validation of MOs,we observed thatZMIZ1a andZMIZ1b MOs caused embryonic developmental delays and malformations in zebrafish.Further analysis of the melanin content in the morphants revealed thatZMIZ1a significantly(49.1%for 0.667 mmol/L inZMIZI1a group,P=0.03)reduced the melanin content in a dose-dependent manner,but only the highest concentration of injectedZMIZ1b MOs significantly(50%for 0.667 mmol/L inZMIZ1b group,P=0.02)reduced the melanin content.A tyrosinase inhibition assay indicated no significant difference between the morphants and wild-type zebrafish.Conclusion:This study successfully modeled a susceptibility gene identified by genome-wide association studies in a zebrafish loss-of-function model and provides insights into the biological mechanism of pigmentation.展开更多
In recent years,pollution caused by the discharge of industrial wastewater into Bohai Bay has posed a potential threat to the health of surrounding residents.Sludge was collected from the outlet of a factory that disc...In recent years,pollution caused by the discharge of industrial wastewater into Bohai Bay has posed a potential threat to the health of surrounding residents.Sludge was collected from the outlet of a factory that discharges effluent into Bohai Bay,and alcohol extracts of sludge(SE)were prepared.We confirmed by UPLC-MS/MS analysis that the SE contained PAHs,including fluorene,pyrene,and phenanthrene.Zebrafish embryos as animal models were exposed to 0.1,0.3,0.5,1 and 5 mg/mL SE from 2 to 4 h post-fertilization(hpf)until 120 hpf.The results showed that SE caused a concentration-dependent increase in mortality and a decrease in hatchability.We found that SE significantly reduced eye pigmentation and decreased the movement of embryos and larvae.In addition,SE decreased triiodothyronine(T3)content and down-regulated the mRNA expression of some thyroid hormone-related genes including TPO and Thrβ,and caused the up-regulation of Dio2 and Dio3 at 120 hpf.Exposure to three individual PAHs found in SE,namely fluorene,pyrene,and phenanthrene,caused morphological and transcriptional changes that were similar to those caused by SE exposure.These findings indicate that PAHs in SE can reduce the pigmentation of zebrafish,which may be related to the genetic changes associated with thyroid hormones,and that zebrafish eye pigmentation can be used as an indicator of PAHs exposure.展开更多
Chlorella meal is a potential protein source for aquafeeds.However,the physiological response of carnivorous fish fed Chlorella meal remains elusive.This study evaluated the effects of replacing dietary fish meal with...Chlorella meal is a potential protein source for aquafeeds.However,the physiological response of carnivorous fish fed Chlorella meal remains elusive.This study evaluated the effects of replacing dietary fish meal with Chlorella meal on growth performance,pigmentation,and liver health in largemouth bass.Five diets were formulated to replace dietary fish meal of 0%(C0,control),25%(C25),50%(C50),75%(C75),and 100%(C100)with Chlorella meal,respectively.Total 300 fish(17.6±0.03 g)were randomly assigned to 15 tanks(3 tanks/group).Fish were fed the experimental diet twice daily for 8 weeks.The increased dietary Chlorella meal quadratically influenced the final body weight(FBW),weight gain rate(WGR),specific growth rate(SGR),and feed intake(FI),which were significantly lower in the C100 group than in the other groups(P<0.05).The feed conversion ratio(FCR)increased linearly or quadratically with dietary Chlorella meal.Dietary Chlorella meal linearly or quadratically increased the lutein content of plasma,liver,and dorsal muscle of largemouth bass(P<0.05).Compared to the C0 group,all supplemented Chlorella meal groups significantly improved the yellowness(b*)of the dorsal body(1.5 to 2.0 fold),abdominal body(1.5 to 1.8 fold),and dorsal muscle(3.8 to 5.4 fold)of largemouth bass(P<0.05).In addition,compared to the C0 group,the liver vacuolation area of fish was significantly increased in the C75 and C100 groups(P<0.05).Transcriptional levels of apoptosis-related genes of b-cell lymphoma-2(bcl2),caspase-9-like(casp9),and caspase-3a(casp3)were markedly upregulated(0.9 to 1.6 fold)in the C100 group compared to the C0 group(P<0.05).Based on the quadratic regression analysis between FBW,WGR,or SGR and dietary Chlorella meal level,largemouth bass had the best growth when replacing 31.7%to 32.6%of fish meal with 15.03%to 15.43%dietary Chlorella meal.The present results indicated that dietary supplementation with Chlorella meal(11.85%to 47.45%)significantly enhanced the pigmentation;however,total replacement of fish meal(40%)with Chlorella meal(47.45%)caused growth retardation,apoptosis,and liver damage in largemouth bass.展开更多
Ostrinia fumacalis (Lepidoptera: Pyralidae) is one of the most destructive agricultural pests in Asia. Traditional pest-management methods include sex pheromone capture, transgenic crops that produce Bacillus thuringi...Ostrinia fumacalis (Lepidoptera: Pyralidae) is one of the most destructive agricultural pests in Asia. Traditional pest-management methods include sex pheromone capture, transgenic crops that produce Bacillus thuringiensis toxin, and pesticides. Although these strategies control pest populations effectively, they also cause negative side effects, including dramatically increased pesticide resistance, severe pollution, and hazards for human health. Recently developed genome editing tools provide new prospects for pest management and have been successfully used in several species. However, few examples have been reported in the agricultural pest O. fumacalis due to a lack in genomic information. In this report, we identified only one transcript of O. fumacalis Argonaute 1 (OfAgo 1) gene from the genome and cloned the open reading frame. OfAgol presented the maximum expression at the embryo stage or in the fat body during the larval stages. To understand its function, an OfAgol mutant was constructed using the Clustered Regularly Interspaced Short Palindromic Repeat/RNA-guided Cas9 nuclease (CRISPR/Cas9). Mutagenesis of OfAgol disrupted cuticle pigmentation by dowregulating micro RNAs and pigmentation-related genes. This is the first report for the cloning and functional analysis of OfAgol, revealing a role of OfAgol in cuticle pigmentation. The current report also established a CRISPR/Cas9 system in O. fumacalisy providing a new insight for pest management.展开更多
Age-related macular degeneration,a multifactorial inflammatory degenerative retinal disease,ranks as the leading cause of blindness in the elderly.Strikingly,there is a scarcity of curative therapies,especially for th...Age-related macular degeneration,a multifactorial inflammatory degenerative retinal disease,ranks as the leading cause of blindness in the elderly.Strikingly,there is a scarcity of curative therapies,especially for the atrophic advanced form of age-related macular degeneration,likely due to the lack of models able to fully recapitulate the native structure of the outer blood retinal barrier,the prime to rget tissue of age-related macular degeneration.Standard in vitro systems rely on 2D monocultures unable to adequately reproduce the structure and function of the outer blood retinal barrier,integrated by the dynamic interaction of the retinal pigment epithelium,the Bruch's membrane,and the underlying choriocapillaris.The Bruch's membrane provides structu ral and mechanical support and regulates the molecular trafficking in the outer blood retinal barrier,and therefo re adequate Bruch's membrane-mimics are key for the development of physiologically relevant models of the outer blood retinal barrie r.In the last years,advances in the field of biomaterial engineering have provided novel approaches to mimic the Bruch's membrane from a variety of materials.This review provides a discussion of the integrated properties and function of outer blood retinal barrier components in healt hy and age-related macular degeneration status to understand the requirements to adequately fabricate Bruch's membrane biomimetic systems.Then,we discuss novel materials and techniques to fabricate Bruch's membrane-like scaffolds for age-related macular degeneration in vitro modeling,discussing their advantages and challenges with a special focus on the potential of Bruch's membrane-like mimics based on decellularized tissue.展开更多
In order to improve the bioavailability of lutein(LUT),a novel lutein-stevio side nanoparticle(LUT-STE)were prepared previously,but the information about LUT-STE on protecting of eye health was limited.This study inve...In order to improve the bioavailability of lutein(LUT),a novel lutein-stevio side nanoparticle(LUT-STE)were prepared previously,but the information about LUT-STE on protecting of eye health was limited.This study investigated the effect of LUT-STE on antioxidant activity of H_(2)O_(2)-induced human retinal pigment epithelial(ARPE)cells.LUT and LUT-STE(final concentration of 5μg/mL)significantly enhanced cell viability from(74.84±5.10)%to(81.92±10.01)%(LUT)and(89.33±4.34)%(LUT-STE),and inhibited the cell apoptosis(P<0.05).After pretreatment with LUT-STE in ARPE cells,the levels of superoxide dismutase(SOD),catalase(CAT)and glutathion peroxidase(GSH-Px)in ARPE cells were significantly increased(P<0.05),the contents of reactive oxygen species(ROS)and malondialdehyde(MDA)were decreased.In addition,the vascular endothelial growth factor(VEGF)levels were inhibited by 13.61%and 17.39%,respectively,pretreatment with LUT and LUT-STE.Western blotting results showed that the pretreatment with LUT-STE inhibited the expression of caspase-9 and caspase-3 and up-regulated Bcl-2/Bax pathway to inhibit H_(2)O_(2)-induced apoptosis.In summary,the novel delivery LUT-STE had more pronounced inhibitory effect on H_(2)O_(2)-induced damage in human ARPE cells.展开更多
AIM:To explore the effects of hepatocyte growth factor(HGF)on retinal pigment epithelium(RPE)cell behaviors.METHODS:The human adult retinal pigment epithelial cell line-19(ARPE-19)were treated by HGF or mesenchymalepi...AIM:To explore the effects of hepatocyte growth factor(HGF)on retinal pigment epithelium(RPE)cell behaviors.METHODS:The human adult retinal pigment epithelial cell line-19(ARPE-19)were treated by HGF or mesenchymalepithelial transition factor(MET)inhibitor SU11274 in vitro.Cell viability was detected by a Cell Counting Kit-8 assay.Cell proliferation and motility was detected by a bromodeoxyuridine incorporation assay and a wound healing assay,respectively.The expression levels of MET,phosphorylated MET,protein kinase B(AKT),and phosphorylated AKT proteins were determined by Western blot assay.The MET and phosphorylated MET proteins were also determined by immunofluorescence assay.RESULTS:HGF increased ARPE-19 cells’viability,proliferation and migration,and induced an increase of phosphorylated MET and phosphorylated AKT proteins.SU11274 significantly reduced cell viability,proliferation,and migration and decreased the expression of MET and AKT proteins.SU11274 suppressed HGF-induced increase of viability,proliferation,and migration in ARPE-19 cells.Additionally,SU11274 also blocked HGF-induced phosphorylation of MET and AKT proteins.CONCLUSION:HGF enhances cellular viability,proliferation,and migration in RPE cells through the MET/AKT signaling pathway,whereas this enhancement is suppressed by the MET inhibitor SU11274.HGF-induced MET/AKT signaling might be a vital contributor of RPE cells survival.展开更多
BACKGROUND The incidence and mortality of colorectal cancer(CRC)are among the highest in the world,and its occurrence and development are closely related to tumor neovascularization.When the balance between pigment ep...BACKGROUND The incidence and mortality of colorectal cancer(CRC)are among the highest in the world,and its occurrence and development are closely related to tumor neovascularization.When the balance between pigment epithelium-derived factors(PEDF)that inhibit angiogenesis and vascular endothelial growth factors(VEGF)that stimulate angiogenesis is broken,angiogenesis is out of control,resulting in tumor development.Therefore,it is very necessary to find more therapeutic targets for CRC for early intervention and later treatment.AIM To investigate the expression and significance of PEDF,VEGF,and CD31-stained microvessel density values(CD31-MVD)in normal colorectal mucosa,adenoma,and CRC.METHODS In this case-control study,we collected archived wax blocks of specimens from the Digestive Endoscopy Center and the General Surgery Department of Chengdu Second People's Hospital from April 2022 to October 2022.Fifty cases of specimen wax blocks were selected as normal intestinal mucosa confirmed by electronic colonoscopy and concurrent biopsy(normal control group),50 cases of specimen wax blocks were selected as colorectal adenoma confirmed by electronic colonoscopy and pathological biopsy(adenoma group),and 50 cases of specimen wax blocks were selected as CRC confirmed by postoperative pathological biopsy after inpatient operation of general surgery(CRC group).An immunohistochemical staining experiment was carried out to detect PEDF and VEGF expression in three groups of specimens,analyze their differences,study the relationship between the two and clinicopathological factors in CRC group,record CD31-MVD in the three groups,and analyze the correlation of PEDF,VEGF,and CD31-MVD in the colorectal adenoma group and the CRC group.The F test or adjusted F test is used to analyze measurement data statistically.Kruskal-Wallis rank sum test was used between groups for ranked data.The chi-square test,adjusted chi-square test,or Fisher's exact test were used to compare the rates between groups.All differences between groups were compared using the Bonferroni method for multiple comparisons.Spearman correlation analysis was used to test the correlation of the data.The test level(α)was 0.05,and a two-sided P<0.05 was considered statistically significant.RESULTS The positive expression rate and expression intensity of PEDF were gradually decreased in the normal control group,adenoma group,and CRC group(100%vs 78%vs 50%,χ^(2)=34.430,P<0.001;++~++vs+~++vs-~+,H=94.059,P<0.001),while VEGF increased gradually(0%vs 68%vs 96%,χ^(2)=98.35,P<0.001;-vs-~+vs++~+++,H=107.734,P<0.001).In the CRC group,the positive expression rate of PEDF decreased with the increase of differen-tiation degree,invasion depth,lymph node metastasis,distant metastasis,and TNM stage(χ^(2)=20.513,4.160,5.128,6.349,5.128,P<0.05);the high expression rate of VEGF was the opposite(χ^(2)=10.317,13.134,17.643,21.844,17.643,P<0.05).In the colorectal adenoma group,the expression intensity of PEDF correlated negatively with CD31-MVD(r=-0.601,P<0.001),whereas VEGF was not significantly different(r=0.258,P=0.07).In the CRC group,the expression intensity of PEDF correlated negatively with the expression intensity of CD31-MVD and VEGF(r=-0.297,P<0.05;r=-0.548,P<0.05),while VEGF expression intensity was positively related to CD31-MVD(r=0.421,P=0.002).CONCLUSION It is possible that PEDF can be used as a new treatment and prevention target for CRC by upregulating the expression of PEDF while inhibiting the expression of VEGF.展开更多
BACKGROUND Diabetic retinopathy(DR)is a major ocular complication of diabetes mellitus,leading to visual impairment.Retinal pigment epithelium(RPE)injury is a key component of the outer blood retinal barrier,and its d...BACKGROUND Diabetic retinopathy(DR)is a major ocular complication of diabetes mellitus,leading to visual impairment.Retinal pigment epithelium(RPE)injury is a key component of the outer blood retinal barrier,and its damage is an important indicator of DR.Receptor for activated C kinase 1(RACK1)activates protein kinase C-ε(PKC-ε)to promote the generation of reactive oxygen species(ROS)in RPE cells,leading to apoptosis.Therefore,we hypothesize that the activation of RACK1 under hypoxic/high-glucose conditions may promote RPE cell apoptosis by modulating PKC-ε/ROS,thereby disrupting the barrier effect of the outer blood retinal barrier and contributing to the progression of DR.AIM To investigate the role and associated underlying mechanisms of RACK1 in the development of early DR.METHODS In this study,Sprague-Dawley rats and adult RPE cell line-19(ARPE-19)cells were used as in vivo and in vitro models,respectively,to explore the role of RACK1 in mediating PKC-εin early DR.Furthermore,the impact of RACK1 on apoptosis and barrier function of RPE cells was also investigated in the former model.RESULTS Streptozotocin-induced diabetic rats showed increased apoptosis and upregulated expression of RACK1 and PKC-εproteins in RPE cells following a prolonged modeling.Similarly,ARPE-19 cells exposed to high glucose and hypoxia displayed elevated mRNA and protein levels of RACK1 and PKC-ε,accompanied by an increases in ROS production,apoptosis rate,and monolayer permeability.However,silencing RACK1 significantly downregulated the expression of PKC-εand ROS,reduced cell apoptosis and permeability,and protected barrier function.CONCLUSION RACK1 plays a significant role in the development of early DR and might serve as a potential therapeutic target for DR by regulating RPE apoptosis and barrier function.展开更多
Arylalkylamine N-acetyltransferase(aaNAT)catalyzes the acetylation of dopamine,5-hydroxy-tryptamine,tryptamine,octopamine,norepinephrine and other ary-lalkylamines to form respective N-acetyl-arylalkylamines.Depending...Arylalkylamine N-acetyltransferase(aaNAT)catalyzes the acetylation of dopamine,5-hydroxy-tryptamine,tryptamine,octopamine,norepinephrine and other ary-lalkylamines to form respective N-acetyl-arylalkylamines.Depending on the products formed,aaNATs are involved in a variety of physiological functions.In the yellow fever mosquito,Aedes aegypti,a number of aaNATs and aaNAT-like proteins have been reported.However,the primary function of each individual aaNAT is yet to be identified.In this study we investigated the function of Ae.aegypti aaNAT 1(Ae-aaNATl)in cuticle pigmentation and development of morphology.Ae-aaNAT1 transcripts were detected at all stages of development with highest expressions after pupation and right before adult eclosion.Ae-aaNATl mutant mosquitoes generated using clustered regularly interspaced palindromic repeats(CRISPR)-CRISPR-associated protein 9 had no obvious effect on larval and pupal development.However,the mutant mosquitoes exhibited a roughened ex-oskeletal surface,darker cuticles,and color pattern changes suggesting that Ae-aaNAT1 plays a role in development of the morphology and pigmentation of Ae.aegypti adult cuticles.The mutant also showed less blood feeding efficiency and lower fecundity when compared with the wild-type.The mutation of Ae-aaNAT1 influenced expression of genes involved in cuticle formation.In summary,Ae-aaNAT1 mainly functions on cuticular pigmentation and also affects blood feeding efficiency and fecundity.展开更多
Tea pigments have significant effects on human health.However,more attention have been paid to their physiological functions.The aim of this study was to analyze the quantitative and qualitative impact of tea pigments...Tea pigments have significant effects on human health.However,more attention have been paid to their physiological functions.The aim of this study was to analyze the quantitative and qualitative impact of tea pigments on human health,together with their current and potential future research directions.The study searched and screened 520 publications on WOS from January 2002 to December 2022.The article collected and collated literature published in the last 20 years and analyzed it bibliometrically for years,journals,countries,authors,topics,keywords and strongest citation bursts.The findings of keywords and strongest citation bursts revealed that the most discussed research topics were anticancer,black tea polyphenol,antioxidant,activator inhibitor,in vivo,gut microbiota,and summarize the relevant literature.As a reference for future research,the literature pointed out current shortcomings and speculated future development trend of tea pigments.展开更多
基金supported by the National Natural Science Foundation of China(No.82073420)the Project of Health and Family Planning Commission of Hunan Province(No.C2019173)+2 种基金the Wisdom Accumulation and Talent Cultivation Project of the Third Xiangya Hospital of Central South University(No.YX202007)the New Xiangya Talent Project of the Third Xiangya Hospital of Central South University(No.20170301)the Fundamental Research Funds for the Central Universities of Central South University(No.2020zzts294),China.
文摘Purpose Skin pigmentation disorders,such as vitiligo and melasma,are difficult to diagnose in the early stages,but abnor-mal tyrosinase levels and tyrosinase activity are potential indicators.Some resorufin-based fluorescence probes(RBFPs)have been designed to detect tyrosinase in tumors,but they have not been used in skin pigmentation disorders.In this study,one of these RBFPs(synthesized by resorufin salt coupled with 3-(bromomethyl)phenol)was evaluated comprehensively.Methods The RBFP was tested in different kinds of mouse and human skin cells,as well as in in vivo models,including zebrafish,guinea pigs,and Sprague-Dawley rats.In addition,small interfering RNAs(siRNAs),kojic acid,and 1-phenyl-2-thiourea(PTU)were used to inhibit tyrosinase levels or tyrosinase activity.Results This probe successfully detected tyrosinase and emitted red fluorescence in melanoma cells and melanocytes.Fluorescence was also observable in zebrafish and on the skin of guinea pigs when using the RBFP.In mouse and human cells,the RBFP showed good selectivity to tyrosinase.Moreover,in the case of decreased tyrosinase levels or activity caused by siRNAs,kojic acid,or PTU,the probe was sensitive to these changes.Further,the RBFP showed no toxic effects at concentrations of<20μmol/L,both in vitro and in vivo.Conclusions Our findings indicate the value and limitations of the RBFP in tyrosinase detection,but suggest the need for further improvement of fluorescent probes in the diagnosis of skin pigmentation disorders.
文摘Beetles in the family Coccinellidae, commonly known as ladybugs, lady beetles, or ladybirds, are easily identifiable and popular beneficial insects. Current research aims to support conservation efforts of beneficial insects in agroecosystems by exploring genetic processes related to nutrition. As a part of this research, colonies of Coleomegilla maculata have been maintained in culture and inbred over many generations since 2009. One result of this inbreeding has been the discovery of novel morphological phenotypes unique to laboratory strains or present in wild populations at such low levels that they have not yet been described. One such phenotype is described here. The strain described here, ye (yellow elytra and eyes) was characterized with classical Mendelian breeding and digital image analysis. This phenotype differs from wild populations by possessing yellow pigment in the elytra and pale grey to white eyes. In contrast, wild populations of C. maculata possess pink or red pigmented elytra with black spots, and black eyes. C. maculata is not known to exhibit polymorphism in the field. Inheritance is autosomal and recessive. This species was not previously known to exhibit the dramatic variation of color described here. The strain is stable in the homozygous recessive form, and retains laboratory rearing characteristics similar to the wild type laboratory strain.
文摘We report the case of a 10-year-old girl with congenital complete heterochromia iridis and segmental pigmentation disorder in its hyperpigmented form. We have found no publication that mentions the combination of these 2 disorders.
文摘Pigmentation of the oral mucosa is relatively common and has a wide variety of etiologies. Although most pigmented lesions of the oral mucosa are associated with deposition of melanin and accidental displacement of a dental alloy, accurate differential diagnosis of a pigmented lesion is important, especially in the case of malignant melanoma. We report two cases of oral mucosal pigmentation associated with accidental displacement of a dental alloy in which malignant melanoma was suspected. Excisional biopsy was carried out in these cases with the incision line set at approximately 5 mm from the lesions. Histopathologically, brownish foreign substances were observed in the lamina propria. Metal quantitative analyses of the extracted specimens were carried out by electron probe microanalysis (EPMA). The metal components and the mass concentration revealed that the metals were derived from a dental casting silver alloy in Case 1 and from a gold-silver palladium alloy in Case 2. Although exogenous pigmentation originating from a dental alloy is not rare, differential diagnosis of oral pigmented lesions is sometimes very difficult. In such cases, histopathological examination may be necessary for the diagnosis to exclude melanocytic lesions and EPMA may be effective to identify the causative dental alloy.
文摘Background: Most data on laser resurfacing have come from studies of people with Fitzpatrick skin types 1 - 3;however, the world’s population is comprised mostly of Fitzpatrick skin types 4 - 6, which are more susceptible to post-inflammatory hyperpigmentation (PIH). Objective: For the purpose of expanding the expertise of plastic surgeons treating patients with darker skin types, this study examined the incidence of PIH in Asians who underwent laser resurfacing, including a histologic arm on fractional ablative resurfacing. Methods & Materials: The clinical study included six subjects of Vietnamese origin who underwent single-depth fractionated CO2 laser resurfacing. The histologic study involved a seventh subject. The MiXto SX®laser with a new scanning handpiece was used, along with magnifying loupes to assess ablative depth after each of three laser passes performed. Photographs were taken at various postoperative intervals. Results: All six clinical subjects showed cosmetic improvement in skin texture and tone with no post-inflammatory hyperpigmentation. In the histologic study, H&E stained sections revealed uniform diathermy. Conclusion: It is possible to significantly reduce PIH in darker skinned subjects through use of a new scanning handpiece and a technique using loupes to assess the depth of ablative resurfacing. The histologic study confirms these findings.
文摘A laboratory colony of Coleomegilla maculata (DeGeer), ye, selected for a pigmentation deficiency, was restored to near wild type cuticle coloration by adding crushed heads and wings of the red colored parental strain to the diet. While the wings and other colored portions of the cuticle re-gained the red color, the eyes of the pigmentation deficient insects were not changed from the pale mutant form. Plant derived carotenes lycopene and beta-carotene did not restore the mutant beetles to a visibly distinguishable red color. An additional pigmentation deficient mutant strain, gold, partially recovered red cuticle color when provided with diet containing pigmented insect particles. This work represents the first rescue of a color phenotype in a lady beetle.
基金supported by the initial funding from Henan University of Urban Construction and a grant from the Foundational and Advanced Techniques Foundation of Henan, China (122300410356).
文摘The pigmentation in the liver of Chinese fire-bellied newt(Cynops orientalis) was described during two periods of the annual cycle(summer activity and winter hibernation). A large number of melanin granules were gathered into clusters and distributed unevenly inside the pigment cells. Liver pigmentation(melanin content) was found unstable,varying during the annual cycle. During the hibernation period,pigmentation accumulation was shown to increase in the liver of the Chinese fire-bellied newt. Hepatocytes during the active period are approximately 14.64% larger than those in the hibernation period,while the nucleus is approximately 7.43% bigger during the active period when compared with that during the hibernation period. These findings indicate that variation in pigment distribution and hepatocyte morphology in Chinese fire-bellied newt liver may be an ecologically adaptive strategy to the adverse physiological conditions during hibernation.
文摘A laboratory colony of <i>Coleomegilla maculata</i> (DeGeer), ye, selected for a pigmentation deficiency, was restored to near wild type cuticle coloration by adding crushed heads and wings of the red colored parental strain to the diet. While the wings and other colored portions of the cuticle re-gained the red color, the eyes of the pigmentation deficient insects were not changed from the pale mutant form. Plant derived carotenes lycopene and beta-carotene did not restore the mutant beetles to a visibly distinguishable red color. An additional pigmentation deficient mutant strain, gold, partially recovered red cuticle color when provided with diet containing pigmented insect particles. This work represents the first rescue of a color phenotype in a lady beetle.
基金the National Key Research and Development Program of China(2021YFD1201601,2021YFF1001201)the earmarked fund for CARS(CARS-04-PSO1)+2 种基金the Agricultural Science and Technology Innovation Program(ASTIP)of the Chinese Academy of Agricultural Sciencesthe National Natural Science Foundation of China(grant no.32201734)the China Postdoctoral Science Foundation(grant no.2021M693465).
文摘Pod coloration is a domestication-related trait in soybean,with modern cultivars typically displaying brown or tan pods,while their wild relative,Glycine soja,possesses black pods.However,the factors regulating this color variation remain unknown.In this study,we cloned and characterized L1,the classical locus responsible for black pods in soybean.By using map-based cloning and genetic analyses,we identified the causal gene of L1 and revealed that it encodes a hydroxymethylglutaryl-coenzyme A(CoA)lyase-like(HMGL-like)domain protein.Biochemical assays showed that L1 functions as a eucomic acid synthase and facilitates the synthesis of eucomic acid and piscidic acid,both of which contribute to coloration of pods and seed coats in soybean.Interestingly,we found that L1 plants are more prone to pod shattering under light exposure than l1 null mutants because dark pigmentation increases photothermal efficiency.Hence,pleiotropic effects of L1 on pod color and shattering,as well as seed pigmentation,likely contributed to the preference forl1 alleles during soybean domestication and improvement.Collectively,our study provides new insights into the mechanism of pod coloration and identifies a new target for future de novo domestication oflegume crops.
基金supported by the Taishan Scholars Program of Shandong Province(No.tsqn201909141)the National Natural Science Foundation of China(Nos.81502736 and 81874244)+1 种基金the Clinical Innovation Project of Jinan,Shandong Provincial Key Research and Development Program(No.2019RKC03002)Shandong Provincial Youth Science and Technology Talents Support Plan,and the Academic promotion program of Shandong First Medical University.
文摘Objective:The zinc finger,MIZ-type containing 1(ZMIZ1)gene has been identified as a possible susceptibility gene associated with vitiligo,therefore we conducted this study to investigate the role ofZMIZ1 in pigmentation.Methods:We generate a zebrafish loss-of-function model using morpholino oligonucleotides(MOs),and two orthologs of humanZMIZ1 have been annotated(ZMIZ1a andZMIZ1b).The expression profiles of ZMIZ1a and ZMIZ1b and their effects on the pigmentation in zebrafish were evaluated by using whole-mount in situ hybridization and melanin quantification.Statistical analysis was performed using the unpaired Studentt-test or one-way analysis.Results:Investigation of the temporal and spatial expressions of these two transcripts suggested that the expressions ofZMIZ1a andZMIZ1b in the brain start to emerge in a ubiquitous fashion from 2 days post-fertilization onwards.After the successful design and validation of MOs,we observed thatZMIZ1a andZMIZ1b MOs caused embryonic developmental delays and malformations in zebrafish.Further analysis of the melanin content in the morphants revealed thatZMIZ1a significantly(49.1%for 0.667 mmol/L inZMIZI1a group,P=0.03)reduced the melanin content in a dose-dependent manner,but only the highest concentration of injectedZMIZ1b MOs significantly(50%for 0.667 mmol/L inZMIZ1b group,P=0.02)reduced the melanin content.A tyrosinase inhibition assay indicated no significant difference between the morphants and wild-type zebrafish.Conclusion:This study successfully modeled a susceptibility gene identified by genome-wide association studies in a zebrafish loss-of-function model and provides insights into the biological mechanism of pigmentation.
基金funded by the National Natural Science Foundation of China(82060672)the Program for Interdisciplinary Innovation team in Inner Mongolia Minzu University,China(Dongwu-2023)the Natural Science Foundation of Inner Mongolia Autonomous Region of China(2020MS08103).
文摘In recent years,pollution caused by the discharge of industrial wastewater into Bohai Bay has posed a potential threat to the health of surrounding residents.Sludge was collected from the outlet of a factory that discharges effluent into Bohai Bay,and alcohol extracts of sludge(SE)were prepared.We confirmed by UPLC-MS/MS analysis that the SE contained PAHs,including fluorene,pyrene,and phenanthrene.Zebrafish embryos as animal models were exposed to 0.1,0.3,0.5,1 and 5 mg/mL SE from 2 to 4 h post-fertilization(hpf)until 120 hpf.The results showed that SE caused a concentration-dependent increase in mortality and a decrease in hatchability.We found that SE significantly reduced eye pigmentation and decreased the movement of embryos and larvae.In addition,SE decreased triiodothyronine(T3)content and down-regulated the mRNA expression of some thyroid hormone-related genes including TPO and Thrβ,and caused the up-regulation of Dio2 and Dio3 at 120 hpf.Exposure to three individual PAHs found in SE,namely fluorene,pyrene,and phenanthrene,caused morphological and transcriptional changes that were similar to those caused by SE exposure.These findings indicate that PAHs in SE can reduce the pigmentation of zebrafish,which may be related to the genetic changes associated with thyroid hormones,and that zebrafish eye pigmentation can be used as an indicator of PAHs exposure.
基金National Natural Science Foundation of China(U21A20266,31972771,31972805,31672670)China Agriculture Research System of MOF and MARA(CARS-46)+2 种基金National Key R&D Program of China(2018YFD0900400)Fund Project in State Key Laboratory of Freshwater Ecology and Biotechnology(2019FBZ02,2019FBZ05)Hubei High-tech Innovation and Business Incubation Center(2019-02-055).
文摘Chlorella meal is a potential protein source for aquafeeds.However,the physiological response of carnivorous fish fed Chlorella meal remains elusive.This study evaluated the effects of replacing dietary fish meal with Chlorella meal on growth performance,pigmentation,and liver health in largemouth bass.Five diets were formulated to replace dietary fish meal of 0%(C0,control),25%(C25),50%(C50),75%(C75),and 100%(C100)with Chlorella meal,respectively.Total 300 fish(17.6±0.03 g)were randomly assigned to 15 tanks(3 tanks/group).Fish were fed the experimental diet twice daily for 8 weeks.The increased dietary Chlorella meal quadratically influenced the final body weight(FBW),weight gain rate(WGR),specific growth rate(SGR),and feed intake(FI),which were significantly lower in the C100 group than in the other groups(P<0.05).The feed conversion ratio(FCR)increased linearly or quadratically with dietary Chlorella meal.Dietary Chlorella meal linearly or quadratically increased the lutein content of plasma,liver,and dorsal muscle of largemouth bass(P<0.05).Compared to the C0 group,all supplemented Chlorella meal groups significantly improved the yellowness(b*)of the dorsal body(1.5 to 2.0 fold),abdominal body(1.5 to 1.8 fold),and dorsal muscle(3.8 to 5.4 fold)of largemouth bass(P<0.05).In addition,compared to the C0 group,the liver vacuolation area of fish was significantly increased in the C75 and C100 groups(P<0.05).Transcriptional levels of apoptosis-related genes of b-cell lymphoma-2(bcl2),caspase-9-like(casp9),and caspase-3a(casp3)were markedly upregulated(0.9 to 1.6 fold)in the C100 group compared to the C0 group(P<0.05).Based on the quadratic regression analysis between FBW,WGR,or SGR and dietary Chlorella meal level,largemouth bass had the best growth when replacing 31.7%to 32.6%of fish meal with 15.03%to 15.43%dietary Chlorella meal.The present results indicated that dietary supplementation with Chlorella meal(11.85%to 47.45%)significantly enhanced the pigmentation;however,total replacement of fish meal(40%)with Chlorella meal(47.45%)caused growth retardation,apoptosis,and liver damage in largemouth bass.
基金National Natural Science Foundation of China (3142010391, 31372257 and 31601903).
文摘Ostrinia fumacalis (Lepidoptera: Pyralidae) is one of the most destructive agricultural pests in Asia. Traditional pest-management methods include sex pheromone capture, transgenic crops that produce Bacillus thuringiensis toxin, and pesticides. Although these strategies control pest populations effectively, they also cause negative side effects, including dramatically increased pesticide resistance, severe pollution, and hazards for human health. Recently developed genome editing tools provide new prospects for pest management and have been successfully used in several species. However, few examples have been reported in the agricultural pest O. fumacalis due to a lack in genomic information. In this report, we identified only one transcript of O. fumacalis Argonaute 1 (OfAgo 1) gene from the genome and cloned the open reading frame. OfAgol presented the maximum expression at the embryo stage or in the fat body during the larval stages. To understand its function, an OfAgol mutant was constructed using the Clustered Regularly Interspaced Short Palindromic Repeat/RNA-guided Cas9 nuclease (CRISPR/Cas9). Mutagenesis of OfAgol disrupted cuticle pigmentation by dowregulating micro RNAs and pigmentation-related genes. This is the first report for the cloning and functional analysis of OfAgol, revealing a role of OfAgol in cuticle pigmentation. The current report also established a CRISPR/Cas9 system in O. fumacalisy providing a new insight for pest management.
基金supported by the Ministry of Science and Innovation of Spain,"Instituto de Salud CarlosⅢ","Fon do de Investigacion Sanitaria" (PI19/00265)funds FEDER"Una manera de hacer Europa" (to BM)。
文摘Age-related macular degeneration,a multifactorial inflammatory degenerative retinal disease,ranks as the leading cause of blindness in the elderly.Strikingly,there is a scarcity of curative therapies,especially for the atrophic advanced form of age-related macular degeneration,likely due to the lack of models able to fully recapitulate the native structure of the outer blood retinal barrier,the prime to rget tissue of age-related macular degeneration.Standard in vitro systems rely on 2D monocultures unable to adequately reproduce the structure and function of the outer blood retinal barrier,integrated by the dynamic interaction of the retinal pigment epithelium,the Bruch's membrane,and the underlying choriocapillaris.The Bruch's membrane provides structu ral and mechanical support and regulates the molecular trafficking in the outer blood retinal barrier,and therefo re adequate Bruch's membrane-mimics are key for the development of physiologically relevant models of the outer blood retinal barrie r.In the last years,advances in the field of biomaterial engineering have provided novel approaches to mimic the Bruch's membrane from a variety of materials.This review provides a discussion of the integrated properties and function of outer blood retinal barrier components in healt hy and age-related macular degeneration status to understand the requirements to adequately fabricate Bruch's membrane biomimetic systems.Then,we discuss novel materials and techniques to fabricate Bruch's membrane-like scaffolds for age-related macular degeneration in vitro modeling,discussing their advantages and challenges with a special focus on the potential of Bruch's membrane-like mimics based on decellularized tissue.
基金the National Natural Science Foundation of China (31801541)the Independent Innovation Fund Project of Agricultural Science and Technology in Jiangsu Province (CX (22)3065)+1 种基金Major Scientific and Technological Achievements Transformation Project of Taizhou (SCG 202105)the Taizhou Science and Technology Support Plan (TN202106)。
文摘In order to improve the bioavailability of lutein(LUT),a novel lutein-stevio side nanoparticle(LUT-STE)were prepared previously,but the information about LUT-STE on protecting of eye health was limited.This study investigated the effect of LUT-STE on antioxidant activity of H_(2)O_(2)-induced human retinal pigment epithelial(ARPE)cells.LUT and LUT-STE(final concentration of 5μg/mL)significantly enhanced cell viability from(74.84±5.10)%to(81.92±10.01)%(LUT)and(89.33±4.34)%(LUT-STE),and inhibited the cell apoptosis(P<0.05).After pretreatment with LUT-STE in ARPE cells,the levels of superoxide dismutase(SOD),catalase(CAT)and glutathion peroxidase(GSH-Px)in ARPE cells were significantly increased(P<0.05),the contents of reactive oxygen species(ROS)and malondialdehyde(MDA)were decreased.In addition,the vascular endothelial growth factor(VEGF)levels were inhibited by 13.61%and 17.39%,respectively,pretreatment with LUT and LUT-STE.Western blotting results showed that the pretreatment with LUT-STE inhibited the expression of caspase-9 and caspase-3 and up-regulated Bcl-2/Bax pathway to inhibit H_(2)O_(2)-induced apoptosis.In summary,the novel delivery LUT-STE had more pronounced inhibitory effect on H_(2)O_(2)-induced damage in human ARPE cells.
基金the Natural Science Foundation of Shaanxi Province(No.2022JM-521)the Science and Technology Plan Project of Xi’an(No.21YXYJ0031).
文摘AIM:To explore the effects of hepatocyte growth factor(HGF)on retinal pigment epithelium(RPE)cell behaviors.METHODS:The human adult retinal pigment epithelial cell line-19(ARPE-19)were treated by HGF or mesenchymalepithelial transition factor(MET)inhibitor SU11274 in vitro.Cell viability was detected by a Cell Counting Kit-8 assay.Cell proliferation and motility was detected by a bromodeoxyuridine incorporation assay and a wound healing assay,respectively.The expression levels of MET,phosphorylated MET,protein kinase B(AKT),and phosphorylated AKT proteins were determined by Western blot assay.The MET and phosphorylated MET proteins were also determined by immunofluorescence assay.RESULTS:HGF increased ARPE-19 cells’viability,proliferation and migration,and induced an increase of phosphorylated MET and phosphorylated AKT proteins.SU11274 significantly reduced cell viability,proliferation,and migration and decreased the expression of MET and AKT proteins.SU11274 suppressed HGF-induced increase of viability,proliferation,and migration in ARPE-19 cells.Additionally,SU11274 also blocked HGF-induced phosphorylation of MET and AKT proteins.CONCLUSION:HGF enhances cellular viability,proliferation,and migration in RPE cells through the MET/AKT signaling pathway,whereas this enhancement is suppressed by the MET inhibitor SU11274.HGF-induced MET/AKT signaling might be a vital contributor of RPE cells survival.
基金The study was approved by the Ethics Committee of the Second People's Hospital of Chengdu.
文摘BACKGROUND The incidence and mortality of colorectal cancer(CRC)are among the highest in the world,and its occurrence and development are closely related to tumor neovascularization.When the balance between pigment epithelium-derived factors(PEDF)that inhibit angiogenesis and vascular endothelial growth factors(VEGF)that stimulate angiogenesis is broken,angiogenesis is out of control,resulting in tumor development.Therefore,it is very necessary to find more therapeutic targets for CRC for early intervention and later treatment.AIM To investigate the expression and significance of PEDF,VEGF,and CD31-stained microvessel density values(CD31-MVD)in normal colorectal mucosa,adenoma,and CRC.METHODS In this case-control study,we collected archived wax blocks of specimens from the Digestive Endoscopy Center and the General Surgery Department of Chengdu Second People's Hospital from April 2022 to October 2022.Fifty cases of specimen wax blocks were selected as normal intestinal mucosa confirmed by electronic colonoscopy and concurrent biopsy(normal control group),50 cases of specimen wax blocks were selected as colorectal adenoma confirmed by electronic colonoscopy and pathological biopsy(adenoma group),and 50 cases of specimen wax blocks were selected as CRC confirmed by postoperative pathological biopsy after inpatient operation of general surgery(CRC group).An immunohistochemical staining experiment was carried out to detect PEDF and VEGF expression in three groups of specimens,analyze their differences,study the relationship between the two and clinicopathological factors in CRC group,record CD31-MVD in the three groups,and analyze the correlation of PEDF,VEGF,and CD31-MVD in the colorectal adenoma group and the CRC group.The F test or adjusted F test is used to analyze measurement data statistically.Kruskal-Wallis rank sum test was used between groups for ranked data.The chi-square test,adjusted chi-square test,or Fisher's exact test were used to compare the rates between groups.All differences between groups were compared using the Bonferroni method for multiple comparisons.Spearman correlation analysis was used to test the correlation of the data.The test level(α)was 0.05,and a two-sided P<0.05 was considered statistically significant.RESULTS The positive expression rate and expression intensity of PEDF were gradually decreased in the normal control group,adenoma group,and CRC group(100%vs 78%vs 50%,χ^(2)=34.430,P<0.001;++~++vs+~++vs-~+,H=94.059,P<0.001),while VEGF increased gradually(0%vs 68%vs 96%,χ^(2)=98.35,P<0.001;-vs-~+vs++~+++,H=107.734,P<0.001).In the CRC group,the positive expression rate of PEDF decreased with the increase of differen-tiation degree,invasion depth,lymph node metastasis,distant metastasis,and TNM stage(χ^(2)=20.513,4.160,5.128,6.349,5.128,P<0.05);the high expression rate of VEGF was the opposite(χ^(2)=10.317,13.134,17.643,21.844,17.643,P<0.05).In the colorectal adenoma group,the expression intensity of PEDF correlated negatively with CD31-MVD(r=-0.601,P<0.001),whereas VEGF was not significantly different(r=0.258,P=0.07).In the CRC group,the expression intensity of PEDF correlated negatively with the expression intensity of CD31-MVD and VEGF(r=-0.297,P<0.05;r=-0.548,P<0.05),while VEGF expression intensity was positively related to CD31-MVD(r=0.421,P=0.002).CONCLUSION It is possible that PEDF can be used as a new treatment and prevention target for CRC by upregulating the expression of PEDF while inhibiting the expression of VEGF.
基金Supported by National Natural Science Foundation of China,No.82260211Key Research and Development Project in Jiangxi Province,No.20203BBG73058Chinese Medicine Science and Technology Project in Jiangxi Province,No.2020A0166.
文摘BACKGROUND Diabetic retinopathy(DR)is a major ocular complication of diabetes mellitus,leading to visual impairment.Retinal pigment epithelium(RPE)injury is a key component of the outer blood retinal barrier,and its damage is an important indicator of DR.Receptor for activated C kinase 1(RACK1)activates protein kinase C-ε(PKC-ε)to promote the generation of reactive oxygen species(ROS)in RPE cells,leading to apoptosis.Therefore,we hypothesize that the activation of RACK1 under hypoxic/high-glucose conditions may promote RPE cell apoptosis by modulating PKC-ε/ROS,thereby disrupting the barrier effect of the outer blood retinal barrier and contributing to the progression of DR.AIM To investigate the role and associated underlying mechanisms of RACK1 in the development of early DR.METHODS In this study,Sprague-Dawley rats and adult RPE cell line-19(ARPE-19)cells were used as in vivo and in vitro models,respectively,to explore the role of RACK1 in mediating PKC-εin early DR.Furthermore,the impact of RACK1 on apoptosis and barrier function of RPE cells was also investigated in the former model.RESULTS Streptozotocin-induced diabetic rats showed increased apoptosis and upregulated expression of RACK1 and PKC-εproteins in RPE cells following a prolonged modeling.Similarly,ARPE-19 cells exposed to high glucose and hypoxia displayed elevated mRNA and protein levels of RACK1 and PKC-ε,accompanied by an increases in ROS production,apoptosis rate,and monolayer permeability.However,silencing RACK1 significantly downregulated the expression of PKC-εand ROS,reduced cell apoptosis and permeability,and protected barrier function.CONCLUSION RACK1 plays a significant role in the development of early DR and might serve as a potential therapeutic target for DR by regulating RPE apoptosis and barrier function.
基金supported by National Natural Science Foundation of China(3186070231960703)Postgraduate Innovation Research Project of General Higher Education in Hainan Province,China(Hyb2018-08).
文摘Arylalkylamine N-acetyltransferase(aaNAT)catalyzes the acetylation of dopamine,5-hydroxy-tryptamine,tryptamine,octopamine,norepinephrine and other ary-lalkylamines to form respective N-acetyl-arylalkylamines.Depending on the products formed,aaNATs are involved in a variety of physiological functions.In the yellow fever mosquito,Aedes aegypti,a number of aaNATs and aaNAT-like proteins have been reported.However,the primary function of each individual aaNAT is yet to be identified.In this study we investigated the function of Ae.aegypti aaNAT 1(Ae-aaNATl)in cuticle pigmentation and development of morphology.Ae-aaNAT1 transcripts were detected at all stages of development with highest expressions after pupation and right before adult eclosion.Ae-aaNATl mutant mosquitoes generated using clustered regularly interspaced palindromic repeats(CRISPR)-CRISPR-associated protein 9 had no obvious effect on larval and pupal development.However,the mutant mosquitoes exhibited a roughened ex-oskeletal surface,darker cuticles,and color pattern changes suggesting that Ae-aaNAT1 plays a role in development of the morphology and pigmentation of Ae.aegypti adult cuticles.The mutant also showed less blood feeding efficiency and lower fecundity when compared with the wild-type.The mutation of Ae-aaNAT1 influenced expression of genes involved in cuticle formation.In summary,Ae-aaNAT1 mainly functions on cuticular pigmentation and also affects blood feeding efficiency and fecundity.
基金funded by Livelihood Plan Project of Department of Science and Technology of Liaoning Province(2021JH2/10300069,2019-ZD-0845)Department of Education of Liaoning Province(LJKZ0918)National College Students’Innovation and Entrepreneurship Training Program(202210163013).
文摘Tea pigments have significant effects on human health.However,more attention have been paid to their physiological functions.The aim of this study was to analyze the quantitative and qualitative impact of tea pigments on human health,together with their current and potential future research directions.The study searched and screened 520 publications on WOS from January 2002 to December 2022.The article collected and collated literature published in the last 20 years and analyzed it bibliometrically for years,journals,countries,authors,topics,keywords and strongest citation bursts.The findings of keywords and strongest citation bursts revealed that the most discussed research topics were anticancer,black tea polyphenol,antioxidant,activator inhibitor,in vivo,gut microbiota,and summarize the relevant literature.As a reference for future research,the literature pointed out current shortcomings and speculated future development trend of tea pigments.