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A retrospective overview of systemic disorders which might be associated with dental pathology is made. They are grouped as follows: (a) congenital dental developmental disorders, (b) chromosomal anomalies, (c) radiations, (d) immune disorders, (e) intoxications, (f) neurological alterations, (g) gastrointestinal diseases, (h) osteodystrophy and associated conditions, (i) skin diseases, (j) metabolic and endocrine disorders, (k) craniofacial malformation syndromes and other congenital general malformations. The associated dental pathology is described in each case.

The TCR signals are essential for T cell activation and proliferation, primarily through the induction of cytokine and cytokine receptors. Several transcription factor families, including NF-κB/Rel, have been implicated in the regulation of cytokine gene expression in T cells in response to antigen, cytokine and mitogenic stimulation. In this study, we show that the mice with a null mutation in the lymphoid-specific c-Rel gene have normal development of lymphoid tissues and T cell compartment. However, T cells derived from the c-Rel knockout mice have several functional abnormalities. The c-Rel-deficient T lymphocytes fail to respond to activation and proliferation signals mediated by the TCR and mitogens in vitro. This is attributed to an impaired production of cytokines IL-2, IL-3 and granulocyte macrophage colony stimulating factor. In addition, the induction of IL-2Rα chain is impaired in the c-Rel-/- T cells. The poor expression of cytokines and IL-2Rα chain correlates with a reduced nuclear translocation of NF-κB components in c-Rel-/- T cells. Since activation is prerequisite for differentiation into effector cells, c-Rel-/- T cells failed to differentiate into cytotoxic T cells or Th cells without rescuing cytokines. However, upon supplement with exogenous IL-2, the c-Rel-/- cytotoxic T lymphocytes are able to execute cytotoxicity and the c-Rel-/- Th cells are capable of providing help to normal B cells. These data suggest that c-Rel is important for inducible cytokine and cytokine receptor expression, and a key regulator of early activation and proliferation in T cells. [ABSTRACT FROM PUBLISHER]

The article focuses on the study which examines the effects of systemic chemotherapy to patients with advanced ovarian carcinoma after radical surgery. Physicians have applied Kaplan-Meier method to analyze the length of the progression-free period and overall survival to cancer patients. Based on statistical analysis, patients who were primarily treated with radical surgery followed by systemic chemotherapy had an average survival of 36 months.

Human primary lens epithelial cultures serve as an in vitro model for posterior capsular opacification (PCO) formation. PCO occurs when residual lens epithelial cells (LECs) migrate and proliferate after cataract surgery, differentiating into fibroblastic and lens fiber-like cells. This study aims to show and compare the bio-macromolecular profiles of primary LEC cultures and postoperative lens epithelia LECs on basal laminas (bls), while also analyzing bls and cultured LECs separately. Using synchrotron radiation-based Fourier transform infrared (SR-FTIR) (Bruker, Karlsruhe, Germany) microspectroscopy at the Spanish synchrotron light source ALBA, we observed that the SR-FTIR measurements were predominantly influenced by the strong collagen absorbance of the bls. Cultured LECs on bls showed a higher collagen contribution, indicated by higher vas CH 3 , CH 2 and CH 3 wagging and deformation, and the C-N stretching of collagen. In contrast, postoperative LECs on bls showed a higher cell contribution, indicated by the vsym CH 2 peak and the ratio between vas CH 2 and vas CH 3 peaks. The primary difference revealed using SR-FTIR is the greater LEC contribution in spectra recorded from postoperative lens epithelia compared to cultured LECs on bls. IR spectra for bl, cultured LECs and postoperative lens epithelia could be valuable for future research.

Pathological tissue on the surface of the retina that can be of different etiology and pathogenesis can cause changes in the retina that have a direct consequence on vision. Tissues of different etiology and pathogenesis have different morphological structures and also different macromolecule compositions usually characteristic of specific diseases. In this study, we evaluated and compared biochemical differences among samples of three different types of epiretinal proliferations: idiopathic epiretinal membrane (ERMi), membranes in proliferative vitreoretinopathy (PVRm), and proliferative diabetic retinopathy (PDRm). The membranes were analyzed by using synchrotron radiation-based Fourier transform infrared micro-spectroscopy (SR-FTIR). We used the SR-FTIR micro-spectroscopy setup, where measurements were set to achieve a high resolution that was capable of showing clear biochemical spectra in biological tissue. We were able to identify differences between PVRm, PDRm, and ERMi in protein and lipid structure; collagen content and collagen maturity; differences in proteoglycan presence; protein phosphorylation; and DNA expression. Collagen showed the strongest expression in PDRm, lower expression in ERMi, and very low expression in PVRm. We also demonstrated the presence of silicone oil (SO) or polydimethylsiloxane in the structure of PVRm after SO endotamponade. This finding suggests that SO, in addition to its many benefits as an important tool in vitreoretinal surgery, could be involved in PVRm formation.

Synchrotron radiation-based Fourier Transform Infrared (SR-FTIR) microspectroscopy is a non-destructive and chemically sensitive technique for the rapid detection of changes in the different components of the cell's biomacromolecular profile. Reactive oxygen species and oxidative stress may cause damage to the DNA, RNA, and proteins in the retinal pigment epithelium (RPE), which can further lead to age-related macular degeneration (AMD) and visual loss in the elderly. In this study, human primary RPEs (hRPEs) were used to study AMD pathogenesis by using an established in vitro cellular model of the disease. Autophagy-a mechanism of intracellular degradation, which is altered during AMD, was studied in the hRPEs by using the autophagy inducer rapamycin and treated with the autophagy inhibitor bafilomycin A1. In addition, oxidative stress was induced by the hydrogen peroxide (H 2 O 2 ) treatment of hRPEs. By using SR-FTIR microspectroscopy and multivariate analyses, the changes in the phosphate groups of nucleic acids, Amide I and II of the proteins, the carbonyl groups, and the lipid status in the hRPEs showed a significantly different pattern under oxidative stress/autophagy induction and inhibition. This biomolecular fingerprint can be evaluated in future drug discovery studies affecting autophagy and oxidative stress in AMD.

The purpose of this work is to examine the structure of the anterior lens epithelial cells (aLECs) of presenile idiopathic cortical cataract to investigate the possible structural reasons for its development. The anterior lens capsules (aLCs: basement membrane and associated lens epithelial cells) were obtained from routine uneventful cataract surgery of 5 presenile cataract patients (16 and 41 years old women and 29, 39, and 45 years old men). None of the patients had family history of cataract, medication, or trauma and they were otherwise healthy. In addition, the patients did not have any other abnormal features in the ocular status except cataract. The aLCs were prepared for scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The most prominent abnormal features observed by SEM for all 5 studied presenile cataract patients were the changes of the aLECs structure with the dents, the selective concavity of some LECs, at their apical side centrally toward the nucleus. In addition, TEM showed the thinning of the lens epithelium with the segmentally concave cells and the compressed and elongated nuclei. Abnormal and distinguishable structural features were observed in the anterior lens epithelium aLECs in all 5 patients with presenile cataract. Disturbed structure of aLECs, regularly present in presenile cataract type is shown that might be associated with water accumulation in the presenile idiopathic cortical cataract lens., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Andjelic, Drašlar, Hvala and Hawlina.)

Ultraviolet (UV) irradiation is an important risk factor in cataractogenesis. Lens epithelial cells (LECs), which are a highly metabolically active part of the lens, play an important role in UV-induced cataractogenesis. The purpose of this study was to characterize cell compounds such as nucleic acids, proteins, and lipids in human UV C-irradiated anterior lens capsules (LCs) with LECs, as well as to compare them with the control, non-irradiated LCs of patients without cataract, by using synchrotron radiation-based Fourier transform infrared (SR-FTIR) micro-spectroscopy. In order to understand the effect of the UV C on the LC bio-macromolecules in a context of cataractogenesis, we used the SR-FTIR micro-spectroscopy setup installed on the beamline MIRAS at the Spanish synchrotron light source ALBA, where measurements were set to achieve a single-cell resolution with high spectral stability and high photon flux. UV C irradiation of LCs resulted in a significant effect on protein conformation with protein formation of intramolecular parallel β-sheet structure, lower phosphate and carboxyl bands in fatty acids and amino acids, and oxidative stress markers with significant increase of lipid peroxidation and diminishment of the asymmetric CH 3 band.

Ca 2+ homeostasis and signaling disturbances are associated with lens pathophysiology and are involved in cataract formation. Here, we explored the spatiotemporal changes in Ca 2+ signaling in lens epithelial cells (LECs) upon local mechanical stimulation, to better understand the LECs' intercellular communication and its association with cataractogenesis. We were interested in if the progression of the cataract affects the Ca 2+ signaling and if modifications of the Ca 2+ homeostasis in LECs are associated with different cataract types. Experiments were done on the human postoperative anterior lens capsule (LC) preparations consisting of the monolayer of LECs on the basement membrane. Our findings revealed that the Ca 2+ signal spreads radially from the stimulation point and that the amplitude of Ca 2+ transients decreases with increasing distance. It is noteworthy that a comparison of signaling characteristics with respect to the degree of cataract progression revealed that, in LCs from more developed cataracts, the Ca 2+ wave propagates faster and the amplitudes of Ca 2+ signals are lower, while their durations are longer. No differences were identified when comparing LCs with regard to the cataract type. Moreover, experiments with Apyrase have revealed that the Ca 2+ signals are not affected by ATP-dependent paracrine communication. Our results indicated that cataract progression is associated with modifications in Ca 2+ signaling in LECs, suggesting the functional importance of altered Ca 2+ signaling of LECs in cataractogenesis.

Cataract is the leading cause of blindness worldwide but the mechanisms involved in the process of cataractogenesis are not yet fully understood. Two most prevalent types of age-related cataracts are nuclear (N) and cortical (C) cataracts. A common environmental factor in most age-related cataracts is believed to be oxidative stress. The lens epithelium, the first physical and biological barrier in the lens, is build from lens epithelial cells (LECs). LECs are important for the maintenance of lens transparency as they control energy production, antioxidative mechanisms and biochemical transport for the whole lens. The purpose of this study is to characterize compounds in LECs originated from N and C cataracts, by using the synchrotron radiation-based Fourier Transform Infrared (SR-FTIR) microspectroscopy, in order to understand the functional importance of their different bio-macromolecules in cataractogenesis. We used the SR-FTIR microspectroscopy setup installed on the beamline MIRAS at the Spanish synchrotron light source ALBA, where measurements were set to achieve single cell resolution, with high spectral stability and high photon flux. The results showed that protein aggregation in form of fibrils was notably pronounced in LECs of N cataracts, while oxidative stress and the lipids peroxidation were more pronounced in LECs of C cataracts.

The prolific lithium battery electrode material lithium iron phosphate (LiFePO 4 ) stores and releases lithium ions by undergoing a crystallographic phase change. Nevertheless, it performs unexpectedly well at high rate and exhibits good cycling stability. We investigate here the ultrafast charging reaction to resolve the underlying mechanism while avoiding the limitations of prevailing electrochemical methods by using a gaseous oxidant to deintercalate lithium from the LiFePO 4 structure. Oxidizing LiFePO 4 with nitrogen dioxide gas reveals structural changes through in situ synchrotron X-ray diffraction and electronic changes through in situ UV/vis reflectance spectroscopy. This study clearly shows that ultrahigh rates reaching 100% state of charge in 10 s does not lead to a particle-wide union of the olivine and heterosite structures. An extensive solid solution phase is therefore not a prerequisite for ultrafast charge/discharge.

A chronic low-level inflammation contributes to the pathogenesis of age-related macular degeneration (AMD), the most common cause of blindness in the elderly in Western countries. The loss of central vision results from attenuated maintenance of photoreceptors due to the degeneration of retinal pigment epithelium (RPE) cells beneath the photoreceptor layer. It has been proposed that pathologic inflammation initiated in RPE cells could be regulated by the activation of type 2 cannabinoid receptors (CB 2 ). Here, we have analysed the effect of CB 2 activation on cellular survival and inflammation in human RPE cells. RPE cells were treated with the selective CB 2 agonist JWH-133 in the presence or absence of the oxidative stressor 4-hydroxynonenal. Thereafter, cellular viability as well as the release of pro-inflammatory cytokines and potential underlying signalling pathways were analysed. Our results show that JWH-133 led to increased intracellular Ca 2+ levels, suggesting that RPE cells are capable of responding to a CB 2 agonist. JWH-133 could not prevent oxidative stress-induced cell death. Instead, 10 µM JWH-133 increased cell death and the release of proinflammatory cytokines in an ERK1/2-dependent manner. In contrast to previous findings, CB 2 activation increased, rather than reduced inflammation in RPE cells.

Purpose: In retinitis pigmentosa (RP) patients, relatively minor lens opacity in central part of posterior pole of the lens may cause disproportionate functional symptoms requiring cataract operation. To investigate the possible structural reasons for this opacity development, we studied the structure of the lens epithelium of patients with RP., Methods: The anterior lens capsule (aLC: basement membrane and associated lens epithelial cells, LECs) was obtained from cataract surgery and prepared for scanning and transmission electron microscopy (SEM and TEM)., Results: Both SEM and TEM show a number of abnormal features in the anterior lens epithelium of cataract patients with RP. The abnormalities appear mainly as holes, thinning and degradation of the epithelium, with the dimensions from <1 μm to more than 50 μm. Other types of holes in size up to 20 μm were seen that may be formed by gradual stretching of the lens epithelium. Another type of abnormalities was cracks that were seen between adjacent LECs, with dimensions 0.1-2 μm × up to 10 μm., Conclusions: Abnormal structural features were observed in the anterior lens epithelium that may cause water influx into the lens. This may lead to clouding along the water clefts leading towards the posterior pole in the RP cataractous lens. We suggest that the lens epithelium has a role in the development of the cataract in patients with RP., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To study the structure of the anterior lens epithelial cells (aLECs) and the contacts of the aLECs with the basal lamina (BL) in order to understand their role in the lens epithelium's function., Methods: The aLCs (BL and associated aLECs) were obtained from routine uneventful cataract surgery, prepared for and studied by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and confocal microscopy., Results: SEM shows that the basal surface of the aLECs (~10-15 μm) is with aLECs foldings (~1-3 μm) and extensions (~0.5-3 μm) attached to the BL. Confocal microscopy images of the basal sections of the aLECs after membrane staining also suggest that the basal part of aLECs has foldings (~1-3 μm). TEM shows in the aLECs basal parts, towards BL, the structures that look like entanglement (~1-4 μm). In cases where there is a swelling of the cytoplasm and offset of the aLECs from the BL, individual extensions (~0.5-2 μm) that extend to the BL are visible by TEM., Conclusions: We provide detail evidence about the structural organization of the aLECs, in particular about their basal side which is in contact with the BL. This is supported by the complementary use of three techniques, SEM, TEM and confocal microscopy, each of them showing the same morphological features, the extensions and the entanglements of the aLECs cytoplasmic membrane at the border with the BL. The basal surface of the aLECs is increased. It suggests the functional importance of the contact between aLECs and BL., (© 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: Our purpose was to study the structure of the lens epithelial cells (LECs) of intumescent white cataracts (IC) in comparison with nuclear cataracts (NC) in order to investigate possible structural reasons for development of IC., Methods: The anterior lens capsule (aLC: basement membrane and associated LECs) were obtained from cataract surgery and prepared for scanning electron microscopy (SEM) and transmission electron microscopy (TEM)., Results: We observed by SEM that in IC, LEC swelling was pronounced with the clefts surrounding the groups of LECs. Another structural feature was spherical formations, that were observed on the apical side of LEC's, towards the fibre cell layer, both by SEM and TEM. Development of these structures, bulging out from the apical cell membrane of the LEC's and disrupting it, could be followed in steps towards the sphere formation. The degeneration of the lens epithelium and the structures of the aLC in IC similar to Morgagnian globules were also observed. None of these structural changes were observed in NC., Conclusions: We show by SEM and TEM that, in IC, LECs have pronounced structural features not observed in NC. This supports the hypothesis that the disturbed structure of LECs plays a role in water accumulation in the IC lens. We also suggest that, in IC, LECs produce bulging spheres that represent unique structures of degenerated material, extruded from the LEC.

Long-term cultures of cornea limbal epithelial stem cells (LESCs) were developed and characterized for future tissue engineering and clinical applications. The limbal tissue explants were cultivated and expanded for more than 3 months in medium containing serum as the only growth supplement and without use of scaffolds. Viable 3D cell outgrowth from the explants was observed within 4 weeks of cultivation. The outgrowing cells were examined by immunofluorescent staining for putative markers of stemness (ABCG2, CK15, CK19 and Vimentin), proliferation (p63α, Ki-67), limbal basal epithelial cells (CK8/18) and differentiated cornea epithelial cells (CK3 and CK12). Morphological and immunostaining analyses revealed that long-term culturing can form stratified 3D tissue layers with a clear extracellular matrix deposition and organization (collagen I, IV and V). The LESCs showed robust expression of p63α, ABCG2, and their surface marker fingerprint (CD117/c-kit, CXCR4, CD146/MCAM, CD166/ALCAM) changed over time compared to short-term LESC cultures. Overall, we provide a model for generating stem cell-rich, long-standing 3D cultures from LESCs which can be used for further research purposes and clinical transplantation.

Neocortical layer VI is critically involved in thalamocortical activity changes during the sleep/wake cycle. It receives dense projections from thalamic nuclei sensitive to the wake-promoting neuropeptides orexins, and its deepest part, layer VIb, is the only cortical lamina reactive to orexins. This convergence of wake-promoting inputs prompted us to investigate how layer VIb can modulate cortical arousal, using patch-clamp recordings and optogenetics in rat brain slices. We found that the majority of layer VIb neurons were excited by nicotinic agonists and orexin through the activation of nicotinic receptors containing α4-α5-β2 subunits and OX2 receptor, respectively. Specific effects of orexin on layer VIb neurons were potentiated by low nicotine concentrations and we used this paradigm to explore their intracortical projections. Co-application of nicotine and orexin increased the frequency of excitatory post-synaptic currents in the ipsilateral cortex, with maximal effect in infragranular layers and minimal effect in layer IV, as well as in the contralateral cortex. The ability of layer VIb to relay thalamocortical inputs was tested using photostimulation of channelrhodopsin-expressing fibers from the orexin-sensitive rhomboid nucleus in the parietal cortex. Photostimulation induced robust excitatory currents in layer VIa neurons that were not pre-synaptically modulated by orexin, but exhibited a delayed, orexin-dependent, component. Activation of layer VIb by orexin enhanced the reliability and spike-timing precision of layer VIa responses to rhomboid inputs. These results indicate that layer VIb acts as an orexin-gated excitatory feedforward loop that potentiates thalamocortical arousal.

A novel, simple, and reproducible method for cultivating pathological tissues obtained from human eyes during surgery was developed using viscoelastic material as a tissue adherent to facilitate cell attachment and expansion and calcium imaging of cultured cells challenged by mechanical and acetylcholine (ACh) stimulation as well as inflammatory studies. Anterior lens capsule-lens epithelial cells (aLC-LECs) from cataract surgery and proliferative diabetic retinopathy (PDR) fibrovascular epiretinal membranes (fvERMs) from human eyes were used in the study. We hereby show calcium signaling in aLC-LECs by mechanical and acetylcholine (ACh) stimulation and indicate presence of ACh receptors in these cells. Furthermore, an ex vivo study model was established for measuring the inflammatory response in fvERMs and aLC-LECs upon TNFα treatment.