Common proteomic profiles of induced pluripotent stem cell-derived three-dimensional neurons and brain tissue from Alzheimer patients

Publication date: Available online 27 April 2018
Source:Journal of Proteomics
Author(s): Mei Chen, Han-Kyu Lee, Lauren Moo, Eugene Hanlon, Thor Stein, Weiming Xia
We established a unique platform for proteomic analysis of cultured three-dimensional (3D) neurons and brain tissue from Alzheimer's disease (AD) patients. We collected peripheral blood mononuclear cells (PBMC), converted PBMC to induced pluripotent stem cell (iPSC) lines, and differentiated the iPSC into human 3D neuro-spheroids. The postmortem brain tissue from the superior frontal cortex, inferior frontal cortex and cerebellum area of the AD patients was compared to the same regions from the control subjects. Proteomic analysis of 3D neuro-spheroids derived from AD subjects revealed the alteration of a number of proteins involved in axon growth, mitochondrial function, and antioxidant defense. Similar analysis of postmortem AD brain tissue revealed significant alteration in proteins involved in oxidative stress, neuro-inflammation, along with proteins related to axonal injury. These results clearly indicate that the dysfunction of 3D neurons from AD patients in our in vitro environment is comparable to the postmortem AD brain tissue in vivo. In conclusion, our study revealed a number of candidate proteins that have important implications in AD pathogenesis and supports the notion that the iPSC-derived 3D neuronal system functions as a model to examine novel aspects of AD pathology.SignificanceIn this study, we present a unique platform for proteomic analysis of induced pluripotent stem cell-derived three dimensional (3D) neurons and compare the results to those from three regions of postmortem brain tissue from Alzheimer's disease patients and normal control subjects. Our results show that the dysfunction of 3D neurons from AD patients in our in vitro environment is comparable to the postmortem AD brain tissue in vivo. Our results revealed several candidate proteins that have important implications in AD pathogenesis.

Graphical abstract

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Catalase A is involved in the response to photooxidative stress in Pseudomonas aeruginosa

Publication date: Available online 27 April 2018
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Viviana Teresa Orlandi, Eleonora Martegani, Fabrizio Bolognese
BackgroundPseudomonas aeruginosa is the etiological agent of systemic and skin infections that are often difficult to treat. Photodynamic therapy (PDT) and, more recently, phototherapy (PT), are emerging among antimicrobial treatments to be combined with antibiotics. Visible light, either alone or combined with a photosensitizer (PS), elicits photooxidative stress that induces microbial death. The response of bacteria to phototherapy seems to involve the antioxidant machinery. This study relies on the effects of detoxifying catalase A (KatA) in response to PDT and PT-induced photooxidative stress.MethodsThe photo- and photodynamic inactivation experiments have been targeted at P. aeruginosa PAO1 and its isogenic derivative katA- mutant. The microorganisms were irradiated by a wide-spectrum halogen-tungsten lamp or light-emitting diodes (LEDs). Two photosensitizers, Tetrakis-(1-methyl-4-pyridyl)-21H, 23porphine, tetra-p-tosylate (TMPyP) porphyrin and Toluidine Blue O (TBO), were applied as part of the photodynamic approach.ResultsP. aeruginosa katA- mutant was more sensitive than wild-type strain PAO1 to wide-spectrum light and blue LED (464 nm) treatments. The complementation of KatA, in katA- mutant, restored the light response of wild-type PAO1. Upon TBO treatment and irradiation by visible light (halogen lamp or LED), the sensitivity of katA- mutant was significant higher (p = 0.028 and p = 0.045, respectively) than that of the PAO1 strain.ConclusionsThis study provides the first ever description of KatA in the response to photooxidative stress induced by photo- and photodynamic therapy.



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Effect of photodynamic therapy as an adjuvant to non-surgical periodontal therapy: periodontal and metabolic evaluation in patients with type 2 diabetes mellitus

Publication date: Available online 27 April 2018
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Flávia Isabela Barbosa, Patrícia Valente Araújo, Lucas José Campos Machado, Cláudia Silami Magalhães, Milena Maria Moreira Guimarães, Allyson Nogueira Moreira
BackgroundThis pilot study aimed to evaluate the effect of antimicrobial photodynamic therapy (aPDT) as an adjuvant to non-surgical periodontal therapy (NSPT) on periodontal status and glycemic control in patients with type 2 diabetes mellitus and generalized chronic periodontitis.MethodsTwelve patients were evaluated at five time points: during the preparation of the patient (T0), during the treatment phase (T1) and after 30 (T2), 90 (T3) and 180 (T4) days. The patients had a mean age of 52.2 years and a 9.58-year history of diabetes, on average, and were divided into two randomized treatment groups: 6 patients received NSPT combined with aPDT (G1) and 6 patients received only NSPT (G2). The aPDT was applied associating the photosensitizing agent methylene blue (10 mg/ ml) with a red laser (660 nm- 40 mW). The total time of exposure was 2 min per tooth.ResultsWhitin the limitation of this study, the results showed that the plaque index reduced significantly only in the control group (p = 0.02) at T2 (30 days). For bleeding on probing, both groups showed a significant reduction between T1 and T2, with no difference between groups G1 and G2. Regarding the probing depth, there were no differences between groups, but the parameters decreased over time when compared to T1. The glycated haemoglobin and fructosamine levels did not significantly differ between or within the groups at any time point.ConclusionWhen NSPT was combined with aPDT, no additional benefits were observed for the periodontal and metabolic clinical parameters.



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Ex vivo assessment of synergic effect of chlorhexidine for enhancing antimicrobial photodynamic therapy efficiency on expression patterns of biofilm-associated genes of Enterococcus faecalis

Publication date: Available online 27 April 2018
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Behnam Bolhari, Maryam Pourhajibagher, Farzaneh Bazarjani, Nasim Chiniforush, Mehdi Rostami Rad, Salma Pirmoazen, Abbas Bahador
BackgroundIt has clearly demonstrated that Enterococcus faecalis, as a persistent microorganism is the major agent in the etiopatogeny of endodontic infections. Recently, the limitations of conventional endodontic therapy have given rise to many attempts to introduce antimicrobial photodynamic therapy (aPDT) as an alternative treatment. The aim of this study was to analyze the ex vivo effect of aPDT in combination with 2.0 % chlorhexidine (CHX) as a conventional therapy on colony count and expression patterns of genes associated with biofilm formation of E. faecalis.Materials and methodsA total of 125 extracted human single-rooted teeth were divide into six groups (A-F; n = 20) and were incubated with E. faecalis. Group A- photosensitizer (indocyanine green [ICG]); B- diode laser; C- aPDT; D- 2.0% CHX; E- aPDT with photosensitizer modified by 2.0% CHX; and F- control group (no procedure was performed). Five remaining teeth were used to confirm the presence of E. faecalis biofilm via scanning electron microscope. Counts of colony forming units (CFUs) in each group were evaluated separately and quantitative real-time PCR (qRT-PCR) was then applied to monitor genes expression of fsrC, efa, and gelE involved in E. faecalis biofilm.ResultsThe results showed that none of the tested groups achieved eradication or inhibition of biofilm. On the other hand, aPDT+2.0% CHX, 2.0% CHX, and ICG- mediated aPDT groups showed significantly less CFU/mL than ICG and diode laser groups. The group with the lowest CFU/mL count was the aPDT+ 2.0% CHX, being statistically different from all other groups that could decrease the expression levels of efa, gelE, and fsrC genes 6.8-, 8.3-, and 12.1-fold, respectively.ConclusionBased on the results, the synergism effect of ICG-aPDT with 2.0% CHX leads to modulation of the virulence of E. faecalis strains biofilm model by suppressing the expression of the genes associated with biofilm formation.



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Photodynamic therapy for Hidradenitis Suppurativa/acne inversa: Case report

Publication date: Available online 27 April 2018
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Yunjie Zhang, Yuguang Yang, Xianbiao Zou
Hidradenitis suppurativa/acne inversa (HS/AI) is a type of chronic suppurative inflammatory reaction of the hair follicles characterized by recurrent dermal abscesses, sinus tracts and scars. So far, there has not been any prospective study proving the efficacy and safety of photodynamic therapy for the disease. In this report, one case of HS/AI achieved resolution of skin lesions, ulcer healing and disappearance of symptoms after nine treatments with 5-aminolevulinic acid photodynamic therapy (ALA-PDT).



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Interplay between elemental imbalance-related PI3K/Akt/mTOR-regulated apoptosis and autophagy in arsenic (III)-induced jejunum toxicity of chicken

Abstract

Arsenic trioxide (As₂O₃), the most toxic form of arsenic found in foodstuffs, is considered a carcinogen for human and animal. But many of the events that occur during its passage through the gastrointestinal tract are uncharted in birds. This study assesses the toxic effect on the jejunum of chicken which subchronically exposed to diets that contain As₂O₃ (0, 0.625, 1.25, 2.5 mg/kg body weight) for 90 days. Electron microscopy, TdT-mediated dUTP nick-end labeling (TUNEL), qPCR, and Western blot were performed. The results showed that mitochondrial fusion and apoptosis inhibiting genes had degressive trends, whereas mitochondrial fission and apoptosis activating genes presented heightened expressions in the treatment group compared with the control (P < 0.05). Subsequently, significant inhibition in PI3K/AKT/mTOR signaling was observed. Moreover, the expression of autophagy markers (LC3-II/LC3-I, Beclin-1) increased time and dose-dependently. Additionally, metabolic disorders of trace elements were detected evidenced by their significant decreases (aluminum, silicon, calcium, manganese, strontium, titanium, lithium, boron, cobalt, mercury, chromium) and increases (arsenic, cadmium, selenium, lead, nickel) on 90 days using inductively coupled plasma mass spectrometer (ICP-MS). It is possible that the changes of trace elements have a hand in the come on and development of arsenism. Taken together, we conjectured that, in chicken jejunum, arsenic led to redistribution of trace elements, promoting apoptosis via regulating mitochondrial dynamics, leading to autophagy through PI3K/AKT/mTOR signal pathways.

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Ammonia production in poultry houses can affect health of humans, birds, and the environment—techniques for its reduction during poultry production

Abstract

Due to greater consumption of poultry products and an increase in exports, more poultry houses will be needed. Therefore, it is important to investigate ways that poultry facilities can coexist in close proximity to residential areas without odors and environmental challenges. Ammonia (NH₃) is the greatest concern for environmental pollution from poultry production. When birds consume protein, they produce uric acid, ultimately converted to NH₃ under favorable conditions. Factors that increase production include pH, temperature, moisture content, litter type, bird age, manure age, relative humidity, and ventilation rate (VR). NH₃ concentration and emissions in poultry houses depend on VR; seasons also have effects on NH₃ production. Modern ventilation systems can minimize NH₃ in enclosed production spaces quickly but increase its emissions to the environment. NH₃ adversely affects the ecosystem, environment, and health of birds and people. Less than 10 ppm is the ideal limit for exposure, but up to 25 ppm is also not harmful. NH₃ can be minimized by housing type, aerobic and anaerobic conditions, manure handling practices, litter amendment, and diet manipulation without affecting performance and production. Antibiotics can minimize NH₃, but consumers have concerns about health effects. Administration of probiotics seems to be a useful replacement for antibiotics. More studies have been conducted on broilers, necessitating the need to evaluate the effect of probiotics on NH₃ production in conjunction with laying hen performance and egg quality. This comprehensive review focuses on research from 1950 to 2018.

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