Stromal and endothelial herpes simplex virus keratitis reactivation in the convalescent period of COVID-19 – A case report

A 73-year-old lady presented with a white spot and redness in the left eye for 1 month and had been treated elsewhere as a case of fungal keratitis. She had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection 2 months before. Her past ocular history and examination gave a probable diagnosis of herpetic stromal and endothelial keratitis. She responded to oral acyclovir and topical steroid, leading to resolution of stromal edema and inflammation. Anterior chamber fluid polymerase chain reaction (PCR) confirmed pathogen herpes simplex virus (HSV)-1. HSV ocular reactivation after coronavirus disease 2019 (COVID-19) has been reported currently. The present report will add knowledge about this potential opportunistic ophthalmic infection during the recovery phase of COVID-19 disease.     

Flowers of Hibiscus rosa-sinensis, a potential source of contragestative agent. III: Interceptive effect of benzene extract in mouse

In mouse, oral administration of the benzene extract of Hibiscus rosa-sinensis flowers at a dose level of 1 gm/kg body weight/day from day 5-8 of gestation led to termination of pregnancy in about 92% of the animals. The effect was associated with a significant fall in peripheral level of progesterone and increase in uterine acid phosphatase activity, as measured on day 10. The ovary exhibited signs of luteolysis, and the corpus luteal delta 5-3 beta -hydroxysteroid dehydrogenase activity decreased markedly. The interceptive effect of the extract was prevented completely by exogenous progesterone (1 mg/mouse/day) or chorionic gonadotropin (1 I.U./mouse/day) and partially (62.5%) by exogenous prolactin (500 micrograms/mouse/day). In unilaterally pregnant mouse having trauma-induced deciduomata in the sterile horn, the extract caused resorption of the fetuses, and regression of the deciduomata accompanied by reduction in weight of the ovaries. Luteolysis, may be due to interference with the luteotropic influence, and a consequent fall in plasma level of progesterone have been suggested as the plausible cause of termination of pregnancy.     

Omega-3 Fatty Acids and Their Interaction with the Gut Microbiome in the Prevention and Amelioration of Type-2 Diabetes

Type-2 diabetes mellitus (T2DM) is often linked with hyperglycemia, disturbed lipid profiles, inflammation, and gut dysbiosis. Omega-3 fatty acid supplementation has a vital role in the management of T2DM. As a result, a better understanding of the potential role of omega-3 fatty acids in the development and progression of T2DM by influencing the intestinal microflora will help to improve the therapeutic intervention for T2DM and related complications. Focusing on the molecular mechanisms and signaling pathways induced by omega-3 fatty acids, this paper attempts to comprehensively review and discuss the putative associations between omega-3 fatty acids, gut dysbiosis, and the pathophysiology of T2DM and its related comorbidities. In addition, we contemplate the importance of gut microbiota in T2DM prevention and treatment and ponder the role of omega-3 fatty acids in T2DM by positively modulating gut microbiota, which may lead to discovery of novel targets and therapeutic strategies thereby paving way for further comprehensive, mechanistic, and clinical studies.     

Interleukin-3, GM-CSF, and TPA induce distinct phosphorylation events in an interleukin 3-dependent multipotential cell line

The mechanism of action of the hemopoietic growth factor, murine interleukin-3 (mIL-3), was investigated using an mIL-3-dependent multipotential hematopoietic cell line, B6SUtA1. Murine granulocyte- macrophage colony-stimulating factor (mGM-CSF) was as potent as mIL-3 in stimulating these cells. In addition, sodium orthovanadate, an inhibitor of phosphotyrosine phosphatase, and 12-O-tetradecanoyl- phorbol-13-acetate (TPA), a known activator of protein kinase C, also stimulated DNA synthesis in these cells, suggesting that protein phosphorylation might be involved in the mechanism of action of mIL-3 and mGM-CSF. To assess this possibility, intact B6SUtA1 cells exposed for brief periods to mIL-3, mGM-CSF, and TPA were analyzed for changes in phosphorylation patterns using metabolic 32P-labeling and antibodies to phosphotyrosine. Both mIL-3 and mGM-CSF induced the serine-specific phosphorylation of a 68-Kd cytosolic protein, whereas all three agents stimulated the serine-specific phosphorylation of a 68-Kd membrane protein. Furthermore, mIL-3 stimulated tyrosine phosphorylation of the 68-Kd membrane protein, as well as of 140-, 90-, 55, and 40-Kd proteins. The 90-Kd protein was also tyrosine phosphorylated in response to mGM-CSF. These phosphotyrosine containing proteins were not detected in TPA-treated cells. These results indicate that protein phosphorylations on tyrosine and serine residues occur in B6SUtA1 cells following short-term incubation with mIL-3 or mGM-CSF and that most of these phosphorylation events are mediated by kinases other than protein kinase C (PkC).     

Extracellular truncations of h beta c, the common signaling subunit for interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-5, lead to ligand-independent activation

The hypothesis that extracellular truncation of the common receptor subunit for interleukin-3 (IL-3), granulocyte-macrophage colony- stimulating factor, and IL-5 (h beta c) can lead to ligand-independent activation was tested by infecting factor-dependent hematopoietic cell lines with retroviruses encoding truncated forms of h beta c. A truncation, resembling that in v-Mpl, and retaining 45 h beta c-derived extracellular residues, led to constitutive activation in the murine myeloid cell line, FDC-P1. However, infection of cells with retrovirus encoding a more severely truncated receptor, retaining only 7 h beta c- derived extracellular residues, did not confer factor independence on these cells. These experiments show that truncation activates the receptor and define a 37-amino acid segment of h beta c (H395-A431) which contains two motifs conserved throughout the cytokine receptor superfamily (consensus Y/H XX R/Q VR and WSXWS), as essential for factor-independent signaling. The mechanism of activation was also investigated in less severe truncations. A receptor that retains the entire membrane-proximal domain (domain 4) also conferred factor independent growth on FDC-P1 cells; however, a retrovirus encoding a truncated form of h beta c having two intact membrane proximal domains did not have this ability, suggesting that domain 3 may have an inhibitory role in h beta c. The ability of these receptors to confer factor independence was cell specific as demonstrated by their inability to confer factor-independent growth when introduced into the murine IL-3-dependent pro-B cell line BaF-B03. These results are consistent with a model in which activation requires unmasking of an interactive receptor surface in domain 4 and association with a myeloid- specific receptor or accessory component. We suggest that in the absence of ligand intramolecular interactions prevent inappropriate signaling.     

Dynamic evaluation of the renin-angiotensin system with captopril in screening for renovascular hypertension

In 69 hypertensive with suspected renovascular hypertension the response of plasma renin and angiotensin I to a single oral dose of Captopril (Captopril test) was determined. In 15 of the 16 patients found to have renal artery stenosis at angiography and cured by either revascularization or nephrectomy, Captopril stimulated both plasma renin activity and plasma angiotensin I to a far greater extent than in the majority of the 53 classified as essential hypertensives. False positives were limited to 8. Sensitivity and specificity were 94% and 85%, respectively. In the same series sequential renal angiophotoscan showed 100% sensitivity but a lower specificity (75%). In comparison, both the sensitivity and the specificity of rapid-sequence intravenous pielography, isotopic renogram and recumbent plasma renin activity were far less satisfactory. It is concluded that this simple, safe and economical test should be preferred to the other diagnostic procedures in the screening of renovascular hypertension. Its use in combination with renal angiophotoscan improves diagnostic reliability.     

High Precision DNA Modification Analysis of HCG9 in Major Psychosis

New epigenetic technologies may uncover etiopathogenic mechanisms of major psychosis. In this study, we applied padlock probe-based ultra-deep bisulfite sequencing for fine mapping of modified cytosines of the HLA complex group 9 (nonprotein coding) gene in the postmortem brains of individuals affected with schizophrenia or bipolar disorder and unaffected controls. Significant differences between patients and controls were detected in both CpG and CpH modifications. In addition, we identified epigenetic age effects, DNA modification differences between sense and anti-sense strands, and demonstrated how DNA modification data can be used in clustering of patient populations. Our findings revealed new epigenetic complexities but also highlighted the potential of DNA modification approaches in the search of heterogeneous causes of major psychiatric disease.Key words: epigenetics, brain, schizophrenia, bipolar disorder, bisulfite sequencing, padlock probes