In Vivo Confocal Microscopy Evaluation in Patients with Keratoconus

Keratoconus is the most common primary corneal ectasia characterized by progressive focal thinning. Patients experience increased irregular astigmatism, decreased visual acuity and corneal sensitivity. Corneal collagen crosslinking (CXL), a minimally invasive procedure, is effective in halting disease progression. Historically, keratoconus research was confined to ex vivo settings. In vivo confocal microscopy (IVCM) has been used to examine the corneal microstructure clinically. In this review, we discuss keratoconus cellular changes evaluated by IVCM before and after CXL. Cellular changes before CXL include decreased keratocyte and nerve densities, disorganized subbasal nerves with thickening, increased nerve tortuosity and shortened nerve fibre length. Repopulation of keratocytes occurs up to 1 year post procedure. IVCM also correlates corneal nerve status to functional corneal sensitivity. Immediately after CXL, there is reduced nerve density and keratocyte absence due to mechanical removal of the epithelium and CXL effect. Nerve regeneration begins after 1 month, with nerve fibre densities recovering to pre-operative levels between 6 months to 1 year and remains stable up to 5 years. Nerves remain tortuous and nerve densities are reduced. Corneal sensitivity is reduced immediately postoperatively but recovers with nerve regeneration. Our article provides comprehensive review on the use of IVCM imaging in keratoconus patients.

Antiproliferative, genotoxic and mutagenic potential of synthetic chocolate food flavoring

Flavoring additives are of great technological importance for the food industry. However, there is little information regarding the toxicological properties of these micro-ingredients, especially at the cellular level. The present study used meristematic root cells of Allium cepa L. to evaluate the toxicity of a liquid, aroma and flavor synthetic chocolate additive, manufactured and widely marketed throughout Brazil and exported to other countries in South America. The flavoring concentrations evaluated were 100.00; 50.00; 25.00; 1.00; 0.50 and 0.25 µL/L, where the highest concentration established was one-hundred times lower than that commercially suggested for use. The concentration 100 µL/L substantially reduced cell division of meristems within 24- and 48-hours exposure. Concentrations from 100.00 to 0.50 µL/L resulted in a significant number of prophases to the detriment of the other phases of cell division, indicating an aneugenic activity, and induced a significant number of cellular changes, with emphasis on micronuclei, nuclear buds and chromosomal breaks. Under the established analysis conditions, with the exception of concentration 0.25 µL/L, the flavoring of chocolate caused cytotoxicity, genotoxicity and mutagenicity to root meristems.

The Role of Autophagy and Mitophagy in Huntington’s Disease

Huntington’s disease (HD) is an inherited autosomal-dominant neurodegenerative disorder that occurs due to mutations in the polyglutamine expansions of the Huntingtin protein (Htt). HD is characterised by the loss of cognitive and motor functions, as well as the development of emotional and psychiatric disturbances. The HD pathology is manifested through the cellular changes that arise due to the toxic functions of mutant Htt (mHtt). Autophagy is a lysosomal pathway that functions to remove damaged intracellular components while mitophagy is a selective form of autophagy involving mitochondria; and PINK1/Parkin-mediated mitophagy is the most well-understood pathway. Mitochondrial dysfunction and defects in mitophagy can be linked to the pathogenesis of HD. Previous research has shown that the presence of mHtt hinders mitophagy; while PINK1/Parkin-mediated mitophagy provides neuroprotection in HD. Hence, this review discusses the roles and regulations of mitophagy, along with an overview of mitophagy in HD.

Pregnancy as a Risk Factor of Severe COVID-19

Since first being identified in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an etiological agent behind Coronavirus disease 19 (COVID-19), has caused three waves of a global pandemic, with a fourth in progress. Despite its high percentage of asymptomatic and low-symptomatic courses of illness, the SARS-CoV-2 pandemic has claimed a higher death toll than the SARS-CoV and MERS-CoV epidemics because of its high infectivity when compared to the other coronaviruses. High COVID-19 mortality is associated with age and other coexisting morbidities, as well as healthcare quality. According to several studies, pregnant women are at a higher risk of severe COVID-19 infection and adverse pregnancy outcomes (caesarean delivery, pre-term birth, low birth weight, preeclampsia, ICU admission, and need for mechanical ventilation). In our review of recent literature, we focused on the effects of COVID-19 in pregnant women, emphasizing the subcellular pathophysiology of SARS-CoV-2. In this paper, we concentrate on the pathophysiology of sub-cellular changes in COVID-19 and endeavor to highlight the aspects that manifest in physiological pregnancy and potentially create a higher risk of SARS-CoV-2 infection and acute COVID-19 symptoms. Understanding how pregnancy-associated changes can cause a synergistic effect with COVID-19 may point us in the right direction for future prophylaxis and treatment for women undergoing COVID-19 during pregnancy.

Cellular Changes in Buccal Mucosa from Farmers Exposed to Glyphosate / Alterações Celulares na Mucosa Bucal de Agricultores Expostos ao Glifosato

This study evaluated the sociodemographic characteristics and behavior of the oral mucosa epithelium exposured to the herbicide glyphosate of family farmers in Cerro Largo, RS, Brazil. 120 individuals were selected for social data collection through interviews. According to the results, most of the interviewees uses glyphosate between 5-10 years, being exposed between 30 minutes to one hour each application and applying the herbicide 1-2 times a year. After the interview, we selected the subjects to the Micronucleus (MN) test. For this test, oral smears were performed in three distinct regions (cheek, mouth floor and tongue edges) of 10 test subjects (exposed to glyphosate, non-smoker and non-alcoholic) and 10 control subjects. Results showed that glyphosate exposure increased the frequency of MN in the test group (p = 0.0002), as well as the frequency of other cellular alterations, such as brokenegg (p = 0.001), binucleation (p = 0.0001) and karyolysis (p = 0.0004). Based on these findings, the extent use of glyphosate may be causing damage to the oral mucosa epithelium and this might respond adaptively through cellular modifications.

The ERK-p38MAPK-STAT3 Signalling Axis Regulates iNOS Expression and Salmonella Infection in Senescent Cells

The cellular changes occurring due to senescence like proliferation arrest, increase in free radical levels, and secretion of pro-inflammatory cytokines have been well studied, but its associated alteration in intracellular signalling networks has been scarcely explored. In this study, we examine the roles of three major kinases viz. p38 MAPK, ERK, and STAT3 in regulating iNOS expression and thereby the levels of the free radical Nitric oxide in senescent cells. Our study revealed that these kinases could differentially regulate iNOS in senescent cells compared to non-senescent cells. Further, we tested the physiological relevance of these alterations with Salmonella infection assays and established an inter-regulatory network between these kinases unique to infected senescent cells. Overall, our findings show how key signalling networks may be rewired in senescent cells rendering them phenotypically different.

Uterine cellular changes during mammalian pregnancy and the evolution of placentation

There are many different forms of nutrient provision in viviparous (live bearing) species. The formation of a placenta is one method where the placenta functions to transfer nutrients from mother to fetus (placentotrophy), transfer waste from the fetus to the mother and respiratory gas exchange. Despite having the same overarching function, there are different types of placentation within placentotrophic vertebrates, and many morphological changes occur in the uterus during pregnancy to facilitate formation of the placenta. These changes are regulated in complex ways but are controlled by similar hormonal mechanisms across species. This review describes current knowledge of the morphological and molecular changes to the uterine epithelium preceding implantation among mammals. Our aim is to identify the commonalities and constraints of these cellular changes to understand the evolution of placentation in mammals and propose directions for future research. We compare and discuss the complex modifications to the ultrastructure of uterine epithelial cells and show that there are similarities in the changes to the cytoskeleton and gross morphology of the uterine epithelial cells, especially of the apical and lateral plasma membrane of the cells during the formation of a placenta in all eutherians and marsupials studied to date. We conclude that further research is needed to understand the evolution of placentation among viviparous mammals, particularly concerning the level of placental invasiveness, hormonal control and genetic underpinnings of pregnancy in marsupial taxa.

Granular Cell Dermatofibroma: When Morphology Still Matters

Dermatofibroma, also known as “fibrous histiocytoma”, is one of the most common cutaneous soft-tissue tumors. Many variants of dermatofibromas have been described, and knowledge of these variations is important to avoid misdiagnosis of a possibly more aggressive tumor. Histological features of different variants can coexist in the same lesion, but typical common fibrous histiocytoma features are generally found, at least focally, in all cases. However, when cellular changes make up the majority of the lesion, the histopathological diagnosis can become more complex and requires immunohistochemical investigations for correct nosographic classification. We present the case of a cutaneous fibrous histiocytoma, “granular cell” variant, found on the left leg of a 74-year-old woman.