Arp2/3 mediated dynamic lamellipodia of the hPSC colony edges promote liposome-based DNA delivery.

Cationic liposome-mediated delivery of drugs, DNA, or RNA plays a pivotal role in small molecule therapy, gene editing, and immunization. However, our current knowledge regarding the cellular structures that facilitate this process remains limited. Here, we used human pluripotent stem cells (hPSCs), which form compact colonies consisting of dynamically active cells at the periphery and epithelial-like cells at the core. We discovered that cells at the colony edges selectively got transfected by cationic liposomes through actin-related protein 2/3 (Arp2/3) dependent dynamic lamellipodia, which is augmented by myosin II inhibition. Conversely, cells at the core establish tight junctions at their apical surfaces, impeding liposomal access to the basal lamellipodia and thereby inhibiting transfection. In contrast, liposomes incorporating mannosylated lipids are internalized throughout the entire colony via receptor-mediated endocytosis. These findings contribute a novel mechanistic insight into enhancing therapeutic delivery via liposomes, particularly in cell types characterized by dynamic lamellipodia, such as immune cells or those comprising the epithelial layer.

Environmental impact on the onset of hypertension-induced end-stage renal disease.

This study intends to assess the impact of environmental factors on the onset of hypertension-induced end-stage renal disease (ESRD) and to compare the level of oxidative stress with nonhypertensive diabetic ESRD. ESRD patients were evaluated along with healthy controls through questionnaire for demographic, nutritional and lifestyle variables. Oxidants were measured along with antioxidants. Multiple linear regression (MLR) models were applied to analyze association of studied variables with oxidants and antioxidants. Most of the hypertensive nephrosclerotic patients were residing in locality that was either closer to industrial belt or polluting water bodies, belonging to low socioeconomic status that invariably affected their lifestyle and nutritional status. Hypertensive ESRD patients showed more pronounced oxidative stress than diabetic ESRD. Several of the studied variables were significantly associated with oxidants and antioxidants. Demographic, nutritional and lifestyle variables appeared to have suggestive effect on the onset of hypertensive nephrosclerosis.

Clinical efficacy of platelet rich plasma in combination with methotrexate in chronic plaque psoriatic patients.

Psoriasis affects up to 3% of the world's population or more than 125 million people. There is an urgent need for new treatment strategy, as up to 50% of patients are not satisfied with current therapies. We evaluated the combined efficiency of platelet rich plasma (PRP) and methotrexate (MTX) in the management of patients with plaque psoriasis. Twenty-one patients with chronic plaque psoriasis were recruited in the study. Sixteen patients were assigned into combinational treatment group (PRP + MTX) and monotherapy group (MTX alone) consisted of five patients. All patients in combinational therapy received autologous PRP in their first sitting and subsequently followed with folitrax-15 for 4 weeks, while patients in monotherapy group received only folitrax-15, all patients received intra-lesional injections. Digital photograph, Psoriasis Area Severity Index (PASI) score and adverse events were recorded at weeks 0, 4, 8, 12 and 16 and were evaluated by three investigators independently. Patients treated with PRP/MTX showed substantial improvement in term of reduction in erythema, induration and desquamation at each visit and was effectively cleared off psoriasis at week 16. Combination treatment of PRP with MTX was well tolerated by all patients without any serious adverse events.

Enhanced mitochondrial biogenesis promotes neuroprotection in human pluripotent stem cell derived retinal ganglion cells.

Mitochondrial dysfunctions are widely afflicted in central nervous system (CNS) disorders with minimal understanding on how to improve mitochondrial homeostasis to promote neuroprotection. Here we have used human stem cell differentiated retinal ganglion cells (hRGCs) of the CNS, which are highly sensitive towards mitochondrial dysfunctions due to their unique structure and function, to identify mechanisms for improving mitochondrial quality control (MQC). We show that hRGCs are efficient in maintaining mitochondrial homeostasis through rapid degradation and biogenesis of mitochondria under acute damage. Using a glaucomatous Optineurin mutant (E50K) stem cell line, we show that at basal level mutant hRGCs possess less mitochondrial mass and suffer mitochondrial swelling due to excess ATP production load. Activation of mitochondrial biogenesis through pharmacological inhibition of the Tank binding kinase 1 (TBK1) restores energy homeostasis, mitigates mitochondrial swelling with neuroprotection against acute mitochondrial damage for glaucomatous E50K hRGCs, revealing a novel neuroprotection mechanism.

Evaluation of Kayser-Fleischer ring in Wilson disease by anterior segment optical coherence tomography.

PURPOSE: The purpose of the study is to present anterior segment optical coherence tomography (AS-OCT) as an alternative method of evaluating Kayser-Fleischer (KF) ring in Wilson disease (WD) not only by ophthalmologists but also by other clinicians dealing with WD. MATERIALS AND METHODS: This was a retrospective case series of six WD patients with KF ring. Evaluation of KF ring was done by naked eye examination using torch light, slit lamp biomicroscopy (SL), and AS-OCT. SL examination was done using a narrow slit of the superior cornea. AS-OCT was done using the Optovue RTvue PremierTM device (Fremont, CA, USA). RESULTS: AS-OCT revealed KF ring as an intense hyperreflective band at the level of Descemet membrane (DM). Color scale of AS-OCT showed KF ring as greenish/greenish yellow/orange yellow/yellowish/red band. Validation of AS-OCT findings was done by second ophthalmologist, medical gastroenterologist, surgical gastroenterologist, and neurophysician. After seeing the first observation, they could identify the AS-OCT features in all pictures with ease. CONCLUSIONS: This is the first observation of KF ring in WD on AS-OCT. On AS-OCT, KF ring is visualized as intense hyperreflectivity at the level of DM in the peripheral cornea. Further, studies are needed to evaluate the usefulness of AS-OCT in WD management.