Morroniside ameliorates lipopolysaccharide-induced inflammatory damage in iris pigment epithelial cells through inhibition of TLR4/JAK2/STAT3 pathway

AIM:To investigate the effect of morroniside(Mor)on lipopolysaccharide(LPS)-treated iris pigment epithelial cells(IPE).METHODS:IPE cells were induced by LPS and treated with Mor.Cell proliferation was detected by cell counting kit(CCK)-8,apoptosis was detected by flow cytometry,the levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,and IL-8 were measured by enzyme-linked immunosorbent assay(ELISA)kits,and the protein expression of TLR4,JAK2,p-JAK2,STAT3,and p-STAT3 was analyzed by Western blotting.In addition,overexpression of TLR4 and Mor treatment of LPS-stimulated IPE cells were also tested for the above indices.RESULTS:Mor effectively promoted the proliferation and inhibited the apoptosis of LPS-treated IPE cells.In addition,Mor significantly reduced the levels of TNF-α,IL-6,and IL-8 and significantly inhibited the expression of TLR4,p-JAK2,and p-STAT3 in LPS-treated IPE cells.The effect of Mor on LPS-treated IPE cells was markedly attenuated after overexpression of TLR4.CONCLUSION:These findings suggest that Mor may ameliorate LPS-induced inflammatory damage and apoptosis in IPE through inhibition of TLR4/JAK2/STAT3 pathway.

Inflammatory myofibroblastic tumor from molecular diagnostics to current treatment

Inflammatory myofibroblastic tumor(IMT)is a rare neoplasm with intermediate malignancy characterized by a propensity for recurrence but a low metastatic rate.Diagnostic challenges arise from the diverse pathological presentation,variable symptomatology,and lack of different imaging features.However,IMT is identified by the fusion of the anaplastic lymphoma kinase(ALK)gene,which is present in approximately 70%of cases,with various fusion partners,including ran-binding protein 2(RANBP2),which allows confirmation of the diagnosis.While surgery is the preferred approach for localized tumors,the optimal long-term treatment for advanced or metastatic disease is difficult to define.Targeted therapies are crucial for achieving sustained response to treatment within the context of genetic alteration in IMT.Crizotinib,an ALK tyrosine kinase inhibitor(TKI),was officially approved by the US Food and Drug Administration(FDA)in 2020 to treat IMT with ALK rearrangement.However,most patients face resistance and disease progression,requiring consideration of sequential treatments.Combining radiotherapy with targeted therapy appears to be beneficial in this indication.Early promising results have also been achieved with immunotherapy,indicating potential for combined therapy approaches.However,defined recommendations are still lacking.This review analyzes the available research on IMT,including genetic disorders and their impact on the course of the disease,data on the latest targeted therapy regimens and the possibility of developing immunotherapy in this indication,as well as summarizing general knowledge about prognostic and predictive factors,also in terms of resistance to systemic therapy.

An overview of pigment gland morphogenesis and its regulatory mechanism

Cotton has enormous economic potential,providing high-quality protein,oil,and fibre.But the comprehensive utilization of cottonseed is limited by the presence of pigment gland and its inclusion.Pigment gland is a common characteristic of Gossypium genus and its relatives,appearing as visible dark opaque dots in most tissues and organs of cotton plants.Secondary metabolites,such as gossypol,synthesized and stored in the cavities of pigment glands act as natural phytoalexins,but are toxic to humans and other monogastric animals.However,only a few cotton genes have been identified as being associated with pigment gland morphogenesis to date,and the developmental processes and regulatory mechanism involved in pigment gland formation remain largely unclear.Here,the research progress on the process of pigment gland morphogenesis and the genetic basis of cotton pigment glands is reviewed,for providing a theoretical basis for cultivating cotton with the ideal pigment gland trait.

Differences between two wheat genotypes in the development of floret primordia and contents of pigments and hormones

Promoting more floret primordia within a spike to acquire fertile potential during the differentiation and pre-dimorphism phases is critical for increasing the number of fertile florets per spike(NFFs).However,it is yet unknown the physiological mechanism regulating the complex and dynamic process.This study aimed to clarify how intra-spike hormones,pigments,and assimilates coordinate with each other to regulate spike morphology and then floret primordia development.A two-year field experiment was conducted with two winter wheat genotypes:N50(big-spike with greater NFFs)and SM22(mediumspike with fewer NFFs).We monitored high temporal and spatial-resolution changes in the number and morphology of floret primordia within a spike,as well as in intra-spike hormones,pigments,and assimilates.Our results revealed that the big-spike genotype had more NFFs than the medium-spike genotype,not only because they had more spikelets,but also because they had greater NFFs mainly at central spikelets.More floret primordia at central spikelets had sufficient time to develop and acquire fertile potential during the differentiation phase(167-176 d after sowing,DAS)and the pre-dimorphism phase(179 DAS)for the big-spike genotype than the medium-spike genotype.Floret primordia with fertile morphology during the pre-dimorphism phase always developed into fertile florets during the dimorphism phase.Those early-developed floret primordia most proximal and intermediate to the rachis in the big-spike genotype developed faster than the medium-spike genotype.Correspondingly,the spike dry matter and pigments(chlorophyll a,chlorophyll b,carotene,and carotenoids)content during 170-182 DAS,auxin(IAA)and cytokinin(CTK)content on 167 DAS were significantly higher in the big-spike genotype than in the medium-spike genotype,while jasmonic acid(JA)content was significantly lower in the big-spike genotype compared to the medium-spike genotype during 167-182 DAS.Since the significant differences in intra-spike hormone content of the two genotypes appear earlier than those in dry matter and pigments,we propose a possible model that helped the N50 genotype(big-spike)to form more fertile florets,taking the intra-spike hormone content as a signaling molecule induced assimilates and pigments synthesis,which accelerated the development of more floret primordia during the differentiation phase and then acquired fertile potential during the pre-dimorphism phase,finally improved the NFFs.Our high temporal and spatial-resolution analysis provides an accurate time window for precision cultivation and effective physiological breeding to improve the number of fertile florets in wheat.

Inhibition of EGFR attenuates EGF-induced activation of retinal pigment epithelium cell via EGFR/AKT signaling pathway

AIM:To explore the effect of epidermal growth factor receptor(EGFR)inhibition by erlotinib and EGFR siRNA on epidermal growth factor(EGF)-induced activation of retinal pigment epithelium(RPE)cells.METHODS:Human RPE cell line(ARPE-19 cells)was activated by 100 ng/mL EGF.Erlotinib and EGFR siRNA were used to intervene EGF treatment.Cellular viability,proliferation,and migration were detected by methyl thiazolyl tetrazolium(MTT)assay,bromodeoxyuridine(BrdU)staining assay and wound healing assay,respectively.EGFR/protein kinase B(AKT)pathway proteins and N-cadherin,α-smooth muscle actin(α-SMA),and vimentin were tested by Western blot assay.EGFR was also determined by immunofluorescence staining.RESULTS:EGF treatment for 24h induced a significant increase of ARPE-19 cells’viability,proliferation and migration,phosphorylation of EGFR/AKT proteins,and decreased total EGFR expression.Erlotinib suppressed ARPE-19 cells’viability,proliferation and migration through down regulating total EGFR and AKT protein expressions.Erlotinib also inhibited EGF-induced an increase of proliferative and migrative ability in ARPE-19 cells and clearly suppressed EGF-induced EGFR/AKT proteins phosphorylation and decreased expression of N-cadherin,α-SMA,and vimentin proteins.Similarly,EGFR inhibition by EGFR siRNA significantly affected EGF-induced an increase of cell proliferation,viability,and migration,phosphorylation of EGFR/AKT proteins,and up-regulation of N-cadherin,α-SMA,and vimentin proteins.CONCLUSION:Erlotinib and EGFR-knockdown suppress EGF-induced cell viability,proliferation,and migration via EGFR/AKT pathway in RPE cells.EGFR inhibition may be a possible therapeutic approach for proliferative vitreoretinopathy(PVR).

Hepatocyte growth factor promotes retinal pigment epithelium cell activity through MET/AKT signaling pathway

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.

Expression and significance of pigment epithelium-derived factor and vascular endothelial growth factor in colorectal adenoma and cancer

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.

Regulation role of miR-204 on SIRT1/VEGF in metabolic memory induced by high glucose in human retinal pigment epithelial cells

AIM:To examine the regulatory role of microRNA-204(miR-204)on silent information regulator 1(SIRT1)and vascular endothelial growth factor(VEGF)under highglucose-induced metabolic memory in human retinal pigment epithelial(hRPE)cells.METHODS:Cells were cultured with either normal(5 mmol/L)or high D-glucose(25 mmol/L)concentrations for 8d to establish control and high-glucose groups,respectively.To induce metabolic memory,cells were cultured with 25 mmol/L D-glucose for 4d followed by culture with 5 mmol/L D-glucose for 4d.In addition,exposed in 25 mmol/L D-glucose for 4d and then transfected with 100 nmol/L miR-204 control,miR-204 inhibitor or miR-204 mimic in 5 mmol/L D-glucose for 4d.Quantitative reverse transcription-polymerase chain reaction(RT-qPCR)was used to detect miR-204 mRNA levels.SIRT1 and VEGF protein levels were assessed by immunohistochemical and Western blot.Flow cytometry was used to investigate apoptosis rate.RESULTS:It was found that high glucose promoted miR-204 and VEGF expression,and inhibited SIRT1 activity,even after the return to normal glucose culture conditions.Upregulation of miR-204 promoted apoptosis inhibiting SIRT1 and increasing VEGF expression.However,downregulation of miR-204 produced the opposite effects.CONCLUSION:The study identifies that miR-204 is the upstream target of SIRT1and VEGF,and that miR-204 can protect hRPE cells from the damage caused by metabolic memory through increasing SIRT1 and inhibiting VEGF expression.

Bone morphogenetic protein-6 suppresses TGF-β_(2)-induced epithelial-mesenchymal transition in retinal pigment epithelium

AIM:To evaluate the effect of bone morphogenetic protein-6(BMP-6)on transforming growth factor(TGF)-β_(2)-induced epithelial-mesenchymal transition(EMT)in retinal pigment epithelium(RPE).METHODS:Adult retinal pigment epithelial cell line(ARPE-19)were randomly divided into control,TGF-β_(2)(5μg/L),and BMP-6 small interfering RNA(siRNA)group.The cell morphology was observed by microscopy,and the cell migration ability were detected by Transwell chamber.The EMT-related indexes and BMP-6 protein levels were detected by Western blotting.Furthermore,a BMP-6 overexpression plasmid was constructed and RPE cells were divided into the control group,TGF-β_(2)+empty plasmid group,BMP-6 overexpression group,and TGF-β_(2)+BMP-6 overexpression group.The EMT-related indexes and extracellular regulated protein kinases(ERK)protein levels were detected.RESULTS:Compared with the control group,the migration of RPE cells in the TGF-β_(2) group was significantly enhanced.TGF-β_(2) increased the protein expression levels ofα-smooth muscle actin(α-SMA),fibronectin and vimentin but significantly decreased the protein levels of E-cadherin and BMP-6(P<0.05)in RPE.Similarly,the migration of RPE cells in the BMP-6 siRNA group was also significantly enhanced.BMP-6 siRNA increased the protein expression levels ofα-SMA,fibronectin and vimentin but significantly decreased the protein expression levels of E-cadherin(P<0.05).Overexpression of BMP-6 inhibited the migration of RPE cells induced by TGF-β_(2) and prevented TGF-β_(2) from affecting EMT-related biomarkers(P<0.05).CONCLUSION:BMP-6 prevents the EMT in RPE cells induced by TGF-β_(2),which may provide a theoretical basis for the prevention and treatment of proliferative vitreoretinopathy.

Relationship between tea pigments and health: A bibliometric and visual analysis

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.

Periorbital Post-Inflammatory Hyperpigmentation after Fractionated CO₂Laser Resurfacing in Asians

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&reg;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.

Pigmentation Restored in Mutant Laboratory Strain of the Lady Beetle Coleomegilla maculata through Dietary Supplementation

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.

Effects of dietary supplementation with algal astaxanthin on growth,pigmentation,and antioxidant capacity of the blood parrot (Cichlasoma citrinellum × Cichlasoma synspilum )

An algal astaxanthin feeding trial was carried out to investigate the ef fects of natural astaxanthin from Haematococcus pluvialis as feed additives on growth, pigmenting efficacy and antioxidant capacity in blood parrot(C ichlasoma citrinellum × C ichlasoma. synspilum). Tissue total antioxidant capacity(TAC), superoxide dismutase(SOD), catalase(CAT) and maleic dialdehyde(MDA) were chosen as measures of its antioxidant capacity. All fish which received an astaxanthin(from micro-algal H. pluvialis) supplemented diet with 400 mg/kg of astaxanthin, after 50 days of feeding, the astaxanthin-fed fish displayed a pinkcolored skin and the control-fed fish displayed a grayish skin. For the growth, the weight gains of controlfed fish and astaxanthin-fed fish were 200% and 300%, respectively. Samples of skin and scales were used for analysis of total carotenoids and astaxanthin content, and fish feeding astaxanthin showed significantly( P <0.05) higher concentrations than the control group, indicating that the pigmentation of this fish had been significantly improved by dietary astaxanthin. Compared with the control fish, pigmented fish had lower SOD, CAT and MDA and higher TAC. It can be concluded that supplementation with dietary astaxanthin could eff ectively enhance growth, skin coloration and the antioxidant capacity of this fish. This study will provide a reference for application of natural astaxanthin from H. pluvialis as feed additives in blood parrot artificial breeding. Our data is also useful in ornamental fish farming, especially when the retentivity of astaxanthin in the skin and scales are involved. It is leading to the possibility of increasing the pigmentation of farmed-fish by adding the powdered form of H. pluvialis to the diet as an ef fective pigment.

Combined effects of light intensity and NH_4^+-enrichment on growth, pigmentation, and photosynthetic performance of Ulva prolifera(Chlorophyta)

The aim of this study was to investigate the effects of light intensity and enhanced nitrogen supply on the growth and photosynthesis of the green-tide macroalga, Ulva prolifera. Thalli of U. prolifera were grown in natural or NH 4 +-enriched seawater under two different light intensities for 7 days, and then the growth rate, pigmentation, and photosynthetic performance of the thalli were evaluated. The results show that the relative growth rate(RGR) was markedly higher under the high light level than under the low light level. Enrichment with NH 4 + enhanced the RGR under high light intensity, but did not affect RGR under low light intensity. In low light conditions, NH 4 +-enrichment resulted in a marked decrease in the maximal photosynthetic rate( P m) and the maximum carbon fixation rate( V max), but it did not affect the half saturation constant for carbon( K 0.5) or the ratio of V max to K 0.5, which reflects the carbon acquisition efficiency. In high light conditions, P m, K 0.5, and the dark respiration rate( R d) increased under NH 4 + enrichment, but V max and the V max / K 0.5 ratio decreased. Regardless of the light intensity, NH 4 +-enrichment did not affect the apparent photosynthetic efficiency( α), which refl ects the ability of the alga to use light energy at low light levels. Under both low and high light intensities, the chlorophyll a(Chl a), chlorophyll b(Chl b), and carotenoids(Car) contents in thalli were higher in NH 4 +-enriched than in natural seawater, except that there was a decrease in the Chl b content of thalli in NH 4 +-enriched seawater under low light intensity. Therefore, NH 4 + enrichment improved the growth and photosynthetic performance of U. prolifera under high light intensity, but not under low light intensity. We discuss the possible mechanisms underlying these physiological responses.

Histological Study of the Liver Pigmentation of Chinese Fire-bellied Newt (Cynops orientalis) During Activity and Hibernation Periods

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.

Segmental Pigmentation Disorder with Congenital Heterochromia Iridis

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.

Role of foliar spray of plant growth regulators in improving photosynthetic pigments and metabolites in Plantago ovata (Psyllium) under salt stress–A field appraisal

Salinity is one of the major abiotic factors that limit the growth and productivity of plants.Foliar application of plant growth regulators(PGRs)may help plants ameliorate the negative impacts of salinity.Thus,a field experiment was conducted at the Botanical Garden University of Balochistan,Quetta,to explore the potential role of PGRs,i.e.,moringa leaf extract(MLE;10%),proline(PRO;1μM),salicylic acid(SA;250μM),and thiourea(TU;10 mM)in ameliorating the impacts of salinity(120 mM)on Plantago ovata,an important medicinal plant.Salinity hampered plant photosynthetic pigments and metabolites but elevated oxidative parameters.However,foliar application of PGRs enhanced photosynthetic pigments,including Chl b(21.11%),carotenoids(57.87%)except Chl a,activated the defense mechanisms by restoring and enhancing the metabolites,i.e.,soluble sugars(49.68%),soluble phenolics(33.34%),and proline(31.47%),significantly under salinity stress.Furthermore,foliar supplementation of PGRs under salt stress led to a decrease of about 43.02%and 43.27%in hydrogen peroxide and malondialdehyde content,respectively.Thus,PGRs can be recommended for improved photosynthetic efficiency and metabolite content that can help to get better yield under salt stress,with the best and most effective treatments being those of PRO and MLE to predominately ameliorate the harsh impacts of salinity.

Oxidative stress in retinal pigment epithelium degeneration:from pathogenesis to therapeutic targets in dry age-related macular degeneration

Age-related macular degeneration is a primary cause of blindness in the older adult population. Past decades of research in the pathophysiology of the disease have resulted in breakthroughs in the form of anti-vascular endothelial growth factor therapies against neovascular age-related macular degeneration;however, effective treatment is not yet available for geographical atrophy in dry agerelated macular degeneration or for preventing the progression from early or mid to the late stage of age-related macular degeneration. Both clinical and experimental investigations involving human agerelated macular degeneration retinas and animal models point towards the atrophic alterations in retinal pigment epithelium as a key feature in age-related macular degeneration progression. Retinal pigment epithelium cells are primarily responsible for cellular-structural maintenance and nutrition supply to keep photoreceptors healthy and functional. The retinal pigment epithelium constantly endures a highly oxidative environment that is balanced with a cascade of antioxidant enzyme systems regulated by nuclear factor erythroid-2-related factor 2 as a main redox sensing transcription factor. Aging and accumulated oxidative stress triggers retinal pigment epithelium dysfunction and eventually death. Exposure to both environmental and genetic factors aggravates oxidative stress damage in aging retinal pigment epithelium and accelerates retinal pigment epithelium degeneration in age-related macular degeneration pathophysiology. The present review summarizes the role of oxidative stress in retinal pigment epithelium degeneration, with potential impacts from both genetic and environmental factors in age-related macular degeneration development and progression. Potential strategies to counter retinal pigment epithelium damage and protect the retinal pigment epithelium through enhancing its antioxidant capacity are also discussed, focusing on existing antioxidant nutritional supplementation, and exploring nuclear factor erythroid-2-related factor 2 and its regulators including REV-ERBα as therapeutic targets to protect against age-related macular degeneration development and progression.

Electron Probe Microanalysis of Exogenous Pigmentation of Oral Mucosa Originating from Dental Alloy: Two Case Reports

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.

Evaluation of a resoruf in-based fluorescent probe for tyrosinase detection in skin pigmentation disorders

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.