How to Fabricate Hyaluronic Acid for Ocular Drug Delivery.

This review aims to examine existing research on the development of ocular drug delivery devices utilizing hyaluronic acid (HA). Renowned for its exceptional biocompatibility, viscoelastic properties, and ability to enhance drug bioavailability, HA is a naturally occurring biopolymer. The review discussed specific mechanisms by which HA enhances drug delivery, including prolonging drug residence time on ocular surfaces, facilitating controlled drug release, and improving drug penetration through ocular tissues.

MG4101, an allogeneic natural killer cell, in patients with relapsed or refractory acute myeloid leukemia: a pilot study.

We evaluated the safety and efficacy of allogeneic, ex-vivo expanded, NK cells, MG4101, in patients with refractory or relapsed AML. The relationship between immunological characteristics and clinical responses was analyzed. Between April 2018 and February 2020, 11 patients (male:female = 5:6) were treated with MG4101.

Phase I Study: Safety and Efficacy of an Ex Vivo-Expanded Allogeneic Natural Killer Cell (MG4101) with Rituximab for Relapsed/Refractory B Cell Non-Hodgkin Lymphoma.

The prognosis of non-Hodgkin lymphoma (NHL) remains poor, with an unmet need for novel therapies. MG4101, an ex vivo-expanded allogeneic natural killer (NK) cell, can enhance rituximab antibody-dependent cytotoxicity in relapsed/refractory (r/r) B cell non-Hodgkin lymphoma. This study assessed the safety and efficacy of MG4101 plus rituximab for patients with r/r NHL.

Moxifloxacin releasing intraocular implant based on a cross-linked hyaluronic acid membrane.

Intraocular antibiotic delivery is an important technique to prevent bacterial infection after ophthalmic surgery, such as cataract surgery. Conventional drug delivery methods, such as antibiotic eye drops, have limitations for intraocular drug delivery due to the intrinsic barrier effect of the cornea. Therefore, frequent instillation of antibiotic eyedrops is necessary to reach a sufficient bactericidal concentration inside the eye.

Adjuvant therapy using -expanded allogenic natural killer cells in hepatectomy patients with hepatitis B virus related solitary hepatocellular carcinoma: MG4101 study.

Backgrounds/aims: Fewer reports have been published regarding hepatectomy patients with solitary hepatocellular carcinoma (HCC) who received immunotherapeutic agents as adjuvant therapy. We evaluated the safety and efficacy of -expanded allogenic natural killer (NK) cells in those patients with modified International Union Against Cancer (UICC) stage T3.

Methods: From August 2014 to October 2015, five patients who underwent hepatic resection received -expanded allogenic NK cells.

Development of a novel hyaluronic acid membrane for the treatment of ocular surface diseases.

Ocular surface diseases (OSD) can cause serious visual deterioration and discomfort. Commercial artificial tear solution containing hyaluronic acid (HA) show excellent biocompatibility and unique viscoelastic characteristics. Here, we developed a novel HA membrane (HAM) by chemical crosslinking using 1,4-butanediol diglycidyl ether for the effective treatment of OSDs.

Safety and immune cell kinetics after donor natural killer cell infusion following haploidentical stem cell transplantation in children with recurrent neuroblastoma.

Introduction: Under the hypothesis that early natural killer cell infusion (NKI) following haploidentical stem cell transplantation (haplo-SCT) will reduce relapse in the early post-transplant period, we conducted a pilot study to evaluate the safety and feasibility of NKI following haplo-SCT in children with recurrent neuroblastoma who failed previous tandem high-dose chemotherapy and autologous SCT.

Methods: We used the high-dose 131I-metaiodobenzylguanidine and cyclophosphamide/fludarabine/anti-thymocyte globulin regimen for conditioning and infused 3 × 107/kg of ex-vivo expanded NK cells derived from a haploidentical parent donor on days 2, 9, and 16 post-transplant. Interleukin-2 was administered (1 × 106 IU/m2/day) subcutaneously to activate infused donor NK cells on days 2, 4, 6, 9, 11, 13, 16, 18, and 20 post-transplant.

Optimization of Large-Scale Expansion and Cryopreservation of Human Natural Killer Cells for Anti-Tumor Therapy.

Allogeneic natural killer (NK) cell therapy is a potential therapeutic approach for a variety of solid tumors. We established an expansion method for large-scale production of highly purified and functionally active NK cells, as well as a freezing medium for the expanded NK cells. In the present study, we assessed the effect of cryopreservation on the expanded NK cells in regards to viability, phenotype, and anti-tumor activity.

BIIB042, a novel γ-secretase modulator, reduces amyloidogenic Aβ isoforms in primates and rodents and plaque pathology in a mouse model of Alzheimer's disease.

Reducing the production of larger aggregation-prone amyloid β-peptides (Aβ) remains an untested therapeutic approach for reducing the appearance and growth of Aβ plaques in the brain, which are a hallmark pathological feature of Alzheimer's disease. γ-Secretase modulators (GSMs) are therapeutics that impact γ-secretase-dependent cleavage of amyloid precursor protein to promote the production of shorter Aβ peptides that are less prone to aggregation and plaque deposition. This is accomplished without inhibiting overall γ-secretase function and cleavage of other substrates, which is believed to be a source of deleterious side effects.

Antibiotic Susceptibility of Staphylococcus aureus in Atopic Dermatitis: Current Prevalence of Methicillin-Resistant Staphylococcus aureus in Korea and Treatment Strategies.

Background: Staphylococcus aureus is a well-known microbe that colonizes or infects the skin in atopic dermatitis (AD). The prevalence of methicillin-resistant S. aureus (MRSA) in AD has recently been increasing.

Clinical course of segmental vitiligo: a retrospective study of eighty-seven patients.

Background: Vitiligo is an acquired disorder characterized by a progressive loss of melanocytes, which is difficult to manage and has an unknown prognosis. The subtype of segmental vitiligo (SV) has been established but it has not been adequately characterized.

Objective: To collect long-term follow-up data for evaluating the clinical course of SV.

Staphylococcus aureus Colonization in Acute and Chronic Skin Lesions of Patients with Atopic Dermatitis.

Background: Staphylococcus aureus (SA) has peculiar abilities to colonize the skin in atopic dermatitis (AD) patients.

Objective: We sought to determine the colonization rates of SA in acute and chronic skin lesions of AD patients, to find any difference in colonization rates according to age and to find the influences of total immunoglobulin E (IgE) and eosinophil counts to the colonization of SA.

Methods: We evaluated the total IgE level and eosinophil counts, and cultured SA from the skin lesions of 687 AD patients (131 acute and 556 chronic skin lesions) and 247 control urticaria patients (July 2009 to November 2010; Samsung Medical Center Dermatology Clinic, Seoul, Korea).

GMP-compliant, large-scale expanded allogeneic natural killer cells have potent cytolytic activity against cancer cells in vitro and in vivo.

Ex vivo-expanded, allogeneic natural killer (NK) cells can be used for the treatment of various types of cancer. In allogeneic NK cell therapy, NK cells from healthy donors must be expanded in order to obtain a sufficient number of highly purified, activated NK cells. In the present study, we established a simplified and efficient method for the large-scale expansion and activation of NK cells from healthy donors under good manufacturing practice (GMP) conditions.

Deregulation of CREB signaling pathway induced by chronic hyperglycemia downregulates NeuroD transcription.

CREB mediates the transcriptional effects of glucose and incretin hormones in insulin-target cells and insulin-producing β-cells. Although the inhibition of CREB activity is known to decrease the β-cell mass, it is still unknown what factors inversely alter the CREB signaling pathway in β-cells. Here, we show that β-cell dysfunctions occurring in chronic hyperglycemia are not caused by simple inhibition of CREB activity but rather by the persistent activation of CREB due to decreases in protein phophatase PP2A.

Cutaneous mastocytosis associated with congenital alopecia.

Mastocytosis is a rare disorder that shows accumulation of mast cells in tissues. Atypical clinical features may mimic impetigo, Langerhans cell histiocytosis, and carcinoid syndrome; however, only 1 case of scarring alopecia associated with mastocytosis has been reported. We present the first case of cutaneous mastocytosis associated with congenital alopecia areata in a 3-year-old Korean girl.

Fumarates promote cytoprotection of central nervous system cells against oxidative stress via the nuclear factor (erythroid-derived 2)-like 2 pathway.

Oxidative stress is central to the pathology of several neurodegenerative diseases, including multiple sclerosis, and therapeutics designed to enhance antioxidant potential could have clinical value. The objective of this study was to characterize the potential direct neuroprotective effects of dimethyl fumarate (DMF) and its primary metabolite monomethyl fumarate (MMF) on cellular resistance to oxidative damage in primary cultures of central nervous system (CNS) cells and further explore the dependence and function of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway in this process. Treatment of animals or primary cultures of CNS cells with DMF or MMF resulted in increased nuclear levels of active Nrf2, with subsequent up-regulation of canonical antioxidant target genes.

Arc/Arg3.1 regulates an endosomal pathway essential for activity-dependent β-amyloid generation.

Assemblies of β-amyloid (Aβ) peptides are pathological mediators of Alzheimer's Disease (AD) and are produced by the sequential cleavages of amyloid precursor protein (APP) by β-secretase (BACE1) and γ-secretase. The generation of Aβ is coupled to neuronal activity, but the molecular basis is unknown. Here, we report that the immediate early gene Arc is required for activity-dependent generation of Aβ.

Discovery of BIIB042, a Potent, Selective, and Orally Bioavailable γ-Secretase Modulator.

We have investigated a novel series of acid-derived γ-secretase modulators as a potential treatment of Alzheimer's disease. Optimization based on cellular potency and brain pharmacodynamics after oral dosing led to the discovery of 10a (BIIB042). Compound 10a is a potent γ-secretase modulator, which lowered Aβ42, increased Aβ38, but had little to no effect on Aβ40 levels both in vitro and in vivo.

Linear Lichen Sclerosus along the Blaschko's Line of the Face.

Lichen sclerosus et atrophicus (LSA) is an inflammatory disease that primarily causes anogenital lesion in middle aged women. We present here a case of facial LSA with an asymptomatic, well-demarcated, whitish to bluish, atrophic patch in a linear pattern on the forehead of a 48-year-old woman. This case showed an atypical clinical presentation and it mimicked en coup de sabre, but the histopathologic results confirmed the diagnosis of LSA.

Resolution of disulfide heterogeneity in Nogo receptor I fusion proteins by molecular engineering.

NgRI (Nogo-66 receptor) is part of a signalling complex that inhibits axon regeneration in the central nervous system. Truncated soluble versions of NgRI have been used successfully to promote axon regeneration in animal models of spinal-cord injury, raising interest in this protein as a potential therapeutic target. The LRR (leucine-rich repeat) regions in NgRI are flanked by N- and C-terminal disulfide-containing 'cap' domains (LRRNT and LRRCT respectively).