RNA-Seq Analysis Reveals an Essential Role of the Tyrosine Metabolic Pathway and Inflammation in Myopia-Induced Retinal Degeneration in Guinea Pigs

Myopia is the second leading cause of visual impairment globally. Myopia can induce sight-threatening retinal degeneration and the underlying mechanism remains poorly defined. We generated a model of myopia-induced early-stage retinal degeneration in guinea pigs and investigated the mechanism of action. Methods: The form-deprivation-induced myopia (FDM) was induced in the right eyes of 2~3-week-old guinea pigs using a translucent balloon for 15 weeks. The left eye remained untreated and served as a self-control. Another group of untreated age-matched animals was used as naïve controls. The refractive error and ocular biometrics were measured at 3, 7, 9, 12 and 15 weeks post-FDM induction. Visual function was evaluated by electroretinography. Retinal neurons and synaptic structures were examined by confocal microscopy of immunolabelled retinal sections. The total RNAs were extracted from the retinas and processed for RNA sequencing analysis. Results: The FDM eyes presented a progressive axial length elongation and refractive error development. After 15 weeks of intervention, the average refractive power was −3.40 ± 1.85 D in the FDM eyes, +2.94 ± 0.59 D and +2.69 ± 0.56 D in the self-control and naïve control eyes, respectively. The a-wave amplitude was significantly lower in FDM eyes and these eyes had a significantly lower number of rods, secretagogin+ bipolar cells, and GABAergic amacrine cells in selected retinal areas. RNA-seq analysis showed that 288 genes were upregulated and 119 genes were downregulated in FDM retinas compared to naïve control retinas. In addition, 152 genes were upregulated and 12 were downregulated in FDM retinas compared to self-control retinas. The KEGG enrichment analysis showed that tyrosine metabolism, ABC transporters and inflammatory pathways were upregulated, whereas tight junction, lipid and glycosaminoglycan biosynthesis were downregulated in FDM eyes. Conclusions: The long-term (15-week) FDM in the guinea pig models induced an early-stage retinal degeneration. The dysregulation of the tyrosine metabolism and inflammatory pathways may contribute to the pathogenesis of myopia-induced retinal degeneration.

Antioxidant properties of topical Caulerpa sp. extract on UVB-induced photoaging in mice

Caulerpa sp., a genus of seaweed native to the Indo-Pacific region, has been known for its antioxidant properties and health benefits when consumed as food. Previous studies have reported Caulerpa sp.’s potential as a strong antioxidant, but its effects on the skin in a topical preparation, especially its role in ultraviolet (UV) protection, have not been studied extensively. Our study investigated the protective effects of 0.2% and 0.4% Caulerpa sp. extract gels on photoaging in the UVB-irradiated skin of Wistar mice. The subjects were divided into naive control, vehicle control, and 3 treatment groups (0.2% Caulerpa sp. extract gel, 0.4% Caulerpa sp. extract gel, and 0.02% astaxanthin gel as a standard antioxidant). The groups, except the naive control group, received a total of 840 mJ/cm2 of UVB irradiation in four weeks. Protective effects of the extract were measured through the evaluation of collagen expression, MMP-1 expression and levels, and 8-OhDG expression. Mice who received topical application of Caulerpa sp. extract gel had higher collagen expression, better-preserved collagen structure, lower levels of MMP-1, and less MMP-1 and 8-OHdG expressions compared to the vehicle control group. There was no difference between different concentrations of the extract. Our findings demonstrated that topical application of Caulerpa sp. extract gel significantly protected UVB-irradiated mice skin from photoaging.

Expansion of prostate epithelial progenitor cells after inflammation of the mouse prostate

Prostatic inflammation is a nearly ubiquitous pathological feature observed in specimens from benign prostate hyperplasia and prostate cancer patients. The microenvironment of the inflamed prostate is highly reactive, and epithelial hyperplasia is a hallmark feature of inflamed prostates. How inflammation orchestrates epithelial proliferation as part of its repair and recovery action is not well understood. Here, we report that a novel epithelial progenitor cell population is induced to expand during inflammation. We used sphere culture assays, immunofluorescence, and flow cytometry to show that this population is increased in bacterially induced inflamed mouse prostates relative to naïve control prostates. We confirmed from previous reports that this population exclusively possesses the ability to regrow entire prostatic structures from single cell culture using renal grafts. In addition, putative progenitor cells harvested from inflamed animals have greater aggregation capacity than those isolated from naïve control prostates. Expansion of this critical cell population requires IL-1 signaling, as IL-1 receptor 1-null mice exhibit inflammation similar to wild-type inflamed animals but exhibit significantly reduced progenitor cell proliferation and hyperplasia. These data demonstrate that inflammation promotes hyperplasia in the mouse prostatic epithelium by inducing the expansion of a selected epithelial progenitor cell population in an IL-1 receptor-dependent manner. These findings may have significant impact on our understanding of how inflammation promotes proliferative diseases such as benign prostatic hyperplasia and prostate cancer, both of which depend on expansion of cells that exhibit a progenitor-like nature.

Surotomycin Demonstrates LowIn VitroFrequency of Resistance and Rapid Bactericidal Activity in Clostridium difficile, Enterococcus faecalis, and Enterococcus faecium

ABSTRACTSurotomycin (CB-183,315) is an orally administered, minimally absorbed, selective bactericidal cyclic lipopeptide in phase 3 development for the treatment ofClostridium difficile-associated diarrhea. The aim of this study was to evaluate the emergence of resistance inC. difficile(ATCC 700057 and three recent clinical isolates from the restriction endonuclease analysis groups BI, BK, and K), vancomycin-susceptible (VS)Enterococcus faecalis(ATCC 49452), vancomycin-resistant (VR)E. faecalis(ATCC 700802), VSEnterococcus faecium(ATCC 6569), and VRE. faecium(ATCC 51559) under anaerobic conditions. The rate of spontaneous resistance was below the limit of detection (<10−8to <10−9) for surotomycin at 16 and 32× the MIC for all isolates tested. Under selective pressure by serial passage,C. difficilegrew in a maximum of 4 μg/ml surotomycin (final MICs of 2 to 8 μg/ml [4- to 16-fold higher than those of the naive control]) at day 15, with the exception of theC. difficileBK strain, which grew in 16 to 32 μg/ml (final MICs of 8 to 32 μg/ml [16- to 64-fold higher than those of the naive control]). Enterococci remained relatively unchanged over 15 days, growing in a maximum of 8 μg/ml surotomycin (final MICs of 2 to 16 μg/ml [8- to 64-fold higher than those of the naive control]). Of the isolates tested, no cross-resistance to vancomycin, rifampin, ampicillin, metronidazole, or moxifloxacin was observed. Surotomycin at 20× MIC demonstrated equally rapid bactericidal activity (≥3-log-unit reduction in CFU/ml in ≤8 h) against naive and reduced-susceptibility isolates ofC. difficile, VSEnterococcus(VSE), and VREnterococcus(VRE), except forC. difficileBK (2.6-log-unit reductions for both). These results suggest that emergence of resistance to surotomycin againstC. difficile,E. faecalis, andE. faeciumis likely to be rare.

Pulmonary surfactant synthesis after unilateral lung injury in mice

Aspiration pneumonitis can lead to alveolar surfactant dysfunction. We employed a murine model of unilateral aspiration to compare surfactant synthesis in the injured (I) and noninjured (NI) contralateral lung. Mice were instilled with hydrochloric acid in the right bronchus and, after 18 h, an intraperitoneal dose of deuterated water was administered as precursor of disaturated phosphatidylcholine (DSPC)-palmitate. Selected bronchoalveolar lavage fluid (BALF) was collected at scheduled time points and lungs were removed. We measured DSPC-palmitate synthesis in lung tissue and secretion in BALF by gas chromatography-isotope ratio mass spectrometry, together with total proteins and myeloperoxidase activity (MPO) by spectrophotometry. BALF total proteins and MPO were significantly increased in the I lungs compared with NI and naïve control lungs. The DSPC pool size was significantly lower in the BALF of the I lungs compared with naïve controls. DSPC synthesis was accelerated in the I and NI lungs. DSPC secretion of the I lungs was similar to their respective naïve controls, and it was markedly lower compared with their respective NI contralateral lungs. DSPC synthesis and secretion were faster, especially in the NI lungs, compared with naïve control lungs, as a possible compensatory mechanism due to a cross-talk between the lungs triggered by inflammation, hyperventilation, and/or undetermined type II cell reaction to the injury.

Mnemonic expertise during wakefulness and sleep

We studied the world's most distinguished experts in the use of mnemonic techniques: the top participants of the World Memory Championships. They neither feel the use of mnemonics to be dreamlike, nor does their REM sleep differ from mnemonic-naive control subjects. Besides these empirical data, also theoretical considerations contradict an isomorphism between features of REM sleep dreaming and mnemonic principles.

A comparative study of the effects of methamphetamine on memory in existing and recovering addicts from a South African population

Memory is a complex of systems by which an organism registers, stores and retrieves exposure to an event or experience. Literature purports that methamphetamine users and dependents have been found to exhibits signs of memory impairment. The aim of the research was to establish the possible existence of significant differences in memory in current methamphetamine users, recovering methamphetamine users, and a matched drug naïve control group. Cognitive functioning was assessed via a neurocognitive test battery that examined the memory of 14 current methamphetamine users, 17 recovering methamphetamine addicts, and 18 drug naïve control participants who were matched according to the demographic variables of age, gender and educational status. The results indicated that recovering methamphetamine users experienced the greatest impairment in memory in comparison to both the control group and current users of methamphetamine. The current users of methamphetamine also experienced some impairment in memory functioning in visual acquisition and retention. The poor performance of the recovering addicts is explained by the juxtaposition of the stimulating and supplemental effect of methamphetamine as experienced by the current users versus the neurotransmitter depletion and structural changes in the brain experienced by the recovering addicts. The control group showed a superior performance since they did not suffer from the neurotoxic effects of methamphetamine.OpsommingGeheue is ‘n komplekse sisteem wat ‘n individu in staat stel om blootstelling aan ‘n voorval of ervarings te registreer, stoor, behou en herroep. Leer- en geheueprobleme is van die mees algemene simptome van neurosielkundige uitvalle in neurologiese en psigiatriese pasiënte. Die literatuur dui aan dat metamfetamienafhanklike verbruikers tipies geheuedisfunksie ervaar. Die doel van die navorsing was om die moontlike voorkoms van verskille in geheuefunksie in huidige gebruikers van metamfetamien, rehabiliterende gebruikers, sowel as ‘n kontrolegroep van dwelmmiddel-naïewe demografies-passende individue te bepaal. Uitvoerende funksie is gemeet met ‘n neurokognitiewe toetsbattery wat die geheuefunksies van 14 huidige gebruikers van metamfetamien, 17 rehabiliterende metamfetamienverslaafde individue en 18 dwelmmiddel-naïewe deelnemers, gepas in terme van ouderdom, geslag en opvoedkundige status, bepaal het. Die resultate dui aan dat dat die rehabiliterende metamfetamiengebruikers die grootste geheueuitvalle getoon het in vergelyking met sowel die huidige gebruikers as die kontrolegroep. Die huidige metamfetamiengebruikers het ook matige geheueuitvalle getoon, spesifiek in visuele leer en retensie. Dit is moontlik dat die geheueuitvalle wat deur metamfetamiengebruikers ervaar word, verband hou met strukturele en funksionele verandering in die breingebiede wat met geheue geassosieer word, as gevolg van metamfetamienvergiftiging. Die swak prestasie van die rehabiliterende metamfetamienverslaafde persone in vergelyking met die huidige gebruikers word verduidelik in terme van die naasmekaarstelling van die stimulerende en aanvullende effek van metamfetamien soos ervaar deur die huidige gebruikers versus die neurotransmitteruitputting en strukturele breinveranderinge in die rehabiliterende individue. Die kontrolegroep het ‘n beter resultaat getoon omdat hulle geen neurotoksiese effekte van metamfetamien gehad het nie.