Ganoderma lucidum, a medicinal fungus is thought to possess and enhance a variety of human immune functions. An immuno-modulatory protein, Ling Zhi-8 (LZ-8) isolated from G. lucidum exhibited potent mitogenic effects upon human peripheral blood lymphocytes (PBL). However, LZ-8-mediated signal transduction in the regulation of interleukin-2 (IL-2) gene expression within human T cells is largely unknown. Here we cloned the LZ-8 gene of G. lucidum, and expressed the recombinant LZ-8 protein (rLZ-8) by means of a yeast Pichia pastoris protein expression system. We found that rLZ-8 induces IL-2 gene expression via the Src-family protein tyrosine kinase (PTK), via reactive oxygen species (ROS), and differential protein kinase-dependent pathways within human primary T cells and cultured Jurkat T cells. In essence, we have established the nature of the rLZ-8-mediated signal-transduction pathways, such as PTK/protein kinase C (PKC)/ROS, PTK/PLC/PKCalpha/ERK1/2, and PTK/PLC/PKCalpha/p38 pathways in the regulation of IL-2 gene expression within human T cells. Our current results of analyzing rLZ-8-mediated signal transduction in T cells might provide a potential application for rLZ-8 as a pharmacological immune-modulating agent.
Genomic alteration can reshape tumor microenvironment to drive tumor malignancy. However, how PTEN deficiency influences microenvironment-mediated cell-cell interactions in glioblastoma (GBM) remains unclear. Here, we show that PTEN deficiency induces a symbiotic glioma-M2 macrophage interaction to support glioma progression. Mechanistically, PTEN -deficient GBM cells secrete high levels of galectin-9 (Gal-9) via the AKT-GSK3β-IRF1 pathway. The secreted Gal-9 drives macrophage M2 polarization by activating its receptor Tim-3 and downstream pathways in macrophages. These macrophages, in turn, secrete VEGFA to stimulate angiogenesis and support glioma growth. Furthermore, enhanced Gal-9/Tim-3 expression predicts poor outcome in glioma patients. In GBM models, blockade of Gal-9/Tim-3 signaling inhibits macrophage M2 polarization and suppresses tumor growth. Moreover, α-lactose attenuates glioma angiogenesis by down-regulating macrophage-derived VEGFA, providing a novel antivascularization strategy. Therefore, our study suggests that blockade of Gal-9/Tim-3 signaling is effective to impair glioma progression by inhibiting macrophage M2 polarization, specifically for PTEN -null GBM.
The coronavirus disease 2019 (COVID 19) pandemic has presented major challenges to ophthalmologists. Reports have shown that ocular manifestations can be the first presenting symptoms of COVID 19 infection and conjunctiva may be a portal of entry for the severe acute respiratory syndrome (SARS) associated coronavirus 2 (SARS CoV 2). The purpose of this article is to provide general guidance for ophthalmologists to understand the prevalence of ocular presentation in COVID 19 patients and to reduce the risk of transmission during practice. Relevant studies published in the period of November 1, 2019, and July 15, 2020, regarding ocular manifestations of COVID 19 and detection of SARS CoV 2 in the eye were included in this systematic review and meta analysis. The pooled prevalence of the ocular manifestations has been estimated at 7% (95% confidence interval [CI]: 0.03–0.10) among COVID 19 patients. The pooled detection rate of SARS CoV 2 from conjunctiva was low (1%, 95% CI: 0.00–0.03). Conjunctival symptoms were the most common ocular manifestations in COVID 19, but the positive detection rate of the SARS CoV 2 virus by reverse transcription–polymerase chain reaction of conjunctival tears or secretions remained low. No study has shown a definite transmission of COVID 19 through ocular mucosa or secretions. In summary, ocular manifestations in COVID 19 patients commonly comprise ocular surface symptoms. Although a low prevalence of ocular symptoms was encountered among patients infected by SARS CoV 2, it is imperative for all ophthalmologists to understand the full spectrum of COVID 19 symptoms or signs including those of the eyes as well as to adopt appropriate protective measures during clinical practice.
BackgroundKabuki syndrome is a multi-system disorder with peculiar facial features, and ophthalmic abnormalities are frequently involved. This case report of a child with Kabuki syndrome describes two new previously unreported ophthalmic conditions.Case presentationA 3-year-old Taiwanese boy with Kabuki syndrome had a short stature, spinal dysraphism, intellectual disability and typical facial features. Ophthalmic findings which have been previously reported in the literature and in this patient, included ptosis, esotropia, coloboma of the iris, retina, choroid and optic disc, and microcornea. The newly identified ophthalmic features in this patient included colobomatous microphthalmos and a dysplastic and elevated disc without central cupping. The genetic analysis identified an MLL2 gene mutation.ConclusionThe presentations of a dysplastic disc and colobomatous microphthalmia are rarely reported in patients with Kabuki syndrome, but these ophthalmic abnormalities may affect vision. Detailed ophthalmic evaluations in children with Kabuki syndrome are advised.
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