Ampio Pharmaceuticals (United States)

Abstract: Niosomes (Niosomes), as Non-Ionic Surfactant (NIOs)-based vesicles, have emerged as versatile nanocarriers in the targeted delivery of drugs due to their biocompatibility, chemical stability, and ability to encapsulate both hydrophilic and lipophilic drugs. Their utility has gained significant traction in addressing challenges associated with conventional therapies, for chronic and resistant diseases, Tuberculosis (TB), and cancer. This review critically evaluates the role of NIOs in the formulation of Niosomes, emphasizing their influence on clinical efficacy, pharma-cokinetics, and targeted drug delivery. It also explores the emerging patent landscape and transla-tional potential of Niosomes systems in TB and oncology. A comprehensive literature and patent database search was conducted using PubMed, Google Scholar, ScienceDirect, Scopus, Elsevier, SpringerLink, and ClinicalTrials.gov, as well as Google Patents, USPTO, and WIPO, covering publications and patents from 20202025 onwards. The relevant studies, clinical trials, and granted patents involving Niosomes formulations with NIOs were systematically analyzed for their for-mulation design, therapeutic outcomes, and disease-specific applications. The study showed a no-table rise in research and patents on Niosomes drug delivery using NIOs categories. In TB, these systems enhanced Bioavailability (BA), sustained drug release, and targeted macrophages. In cancer therapy, they enabled controlled release, minimized side effects, and improved tumor tar-geting. The recent patents highlight advances in combination therapies, responsive systems, and ligand-based targeting, reflecting a trend toward personalized medicine. NIOs play a critical role in modulating the performance of Niosomes drug carriers. Their strategic application in TB and oncology represents a promising avenue for improving therapeutic outcomes. Continued research and innovation in this field, as reflected by patent trends, highlight the translational potential of NIO-based Niosomes formulations toward clinical use.

Abstract Background: The low molecular weight fraction of human serum albumin (LMWF5A) has immunomodulatory activity via its effects on multiple inflammatory mediators and is currently being evaluated for the treatment of hyperactive or persistent inflammatory conditions. To gain further insight into the mechanism of action (MOA) of LMWF5A, an investigation of its effects on activated immune cells was performed. Methods and Results: Peripheral blood mononuclear cells (PBMC) were treated with vehicle control or LMWF5A and stimulated with lipopolysaccharide (LPS), LPS/interferon γ, or interleukin (IL)-4/IL-13, and RNAseq was performed to determine differentially expressed genes (DEGs) within each condition. Unbiased Ingenuity Pathway Analysis (IPA) of DEGs revealed anti-inflammatory and pro-resolving activities for LMWF5A. Moreover, comparison to all IPA upstream regulators predicted that the LMWF5A MOA is opposite to pro-inflammatory regulators and significantly matches the activity of several anti-inflammatory molecules. These analyses identified the glucocorticoid dexamethasone (DEX) as the most significantly similar regulator to LMWF5A. To further explore similarities to DEX, LMWF5A DEGs were compared to two publicly available datasets of activated, DEX-treated PBMC. These comparisons showed continuity between predicted upstream regulators, affording further support to the hypothesis that LMWF5A acts in a manner like DEX. Nevertheless, not all LMWF5A-targeted DEGs showed directional regulation identical to DEX. Conclusions: This study further defines the MOA of LMWF5A and provides hypotheses for future investigations. Because of its predicted similar biological effects and known safety profile, LMWF5A could potentially be used to treat conditions that are supported for DEX with fewer or less harmful side effects.

Abstract The low molecular weight fraction of human serum albumin (LMWF5A) has proven immunomodulatory activity via its effects on multiple inflammatory mediators and transcription factors. This biologic drug is currently being evaluated for the treatment of conditions characterized by hyperactive or persistent immune responses. To gain further insight into the mechanism of action of LMWF5A, an unbiased investigation of its effects on activated immune cells was performed. Peripheral blood mononuclear cells (PBMC) were treated with vehicle control or LMWF5A and stimulated with lipopolysaccharide (LPS), LPS/interferon γ, or interleukin (IL)-4/IL-13 for 24h. Differential gene expression analysis by RNAseq was performed to determine transcriptional changes due to LMWF5A treatment in each stimulation condition. Ingenuity Pathway Analysis software was employed to reveal overall biological trends observed in the RNAseq datasets and to identify compounds with comparable or contrasting activities to LMWF5A. Analysis of each RNA dataset revealed broad anti-inflammatory and pro-resolving activities for LMWF5A, with predicted inhibition of key pro-inflammatory mediators and functions as well as activation of some anti-inflammatory mediators. Upstream regulator analysis confirmed these activities and identified the corticosteroid dexamethasone as the most significantly similar regulator. Further comparison of LMWF5A and dexamethasone revealed similar, but not identical, targets and directional regulation. This study supports our current knowledge on the mode of action of LMWF5A and provides new hypotheses for future investigations. Due to its analogous biological effects with dexamethasone and known safety profile, LMWF5A may be used to treat conditions that are supported for dexamethasone with fewer or less harmful side effects.

Traumatic joint injury induces chondrocyte dysfunction and progressive breakdown of articular cartilage, leading to post-traumatic osteoarthritis (PTOA). In this condition, dysfunctional fibroblast-like chondrocytes (FLCs) no longer express proteins required for cartilage maintenance, such as SOX9 and collagen-type II (COL2). Interleukin-6 (IL-6) has been demonstrated to downregulate expression of these two critical proteins in chondrocytes, and increased IL-6 levels have been measured in patients with PTOA. The <5kDa fraction of human serum albumin (LMWF5A) has been suggested to modulate this pathway, as decreased levels of IL-6 are secreted by immunostimulated LMWF5A-treated macrophages. Our objective was to determine whether LMWF5A induces an in vitro model of FLCs to redifferentiate into functional chondrocytes. SOX9 and COL2 were monitored via western blot, and COL2 was detected with immunofluorescence. Aggrecan and IL-6 were quantified by ELISA. Glycosaminoglycan (GAG) levels were quantified with alcian blue. We found that LMWF5A significantly increases the principal cartilage transcription factor SOX9 and the SOX9 target protein COL2 in monolayer-cultured FLCs. Multiple LMWF5A treatments of 3-D pellet FLC cultures over 2wks resulted in a significant decrease in IL-6 and significant increases in the major players of articular cartilage mechanics, aggrecan and highly-sulfated GAGs. These data support the hypothesis and clinical outcomes of two phase III clinical trials that LMWF5A-treatment induces chondrogenesis and supports functional cartilage. We propose that LMWF5A could maintain articular cartilage integrity in all joints following traumatic injury.

Este trabalho teve como objetivo a estruturação de hipóteses e somas de quadrados a elas associadas, com dados desbalanceados, visando orientar a utilização de alguns pacotes estatísticos por usuários não iniciados em estatística. Para tanto, foram revistos métodos de análise de dados desbalanceados, e adotado o modelo estatístico: y = Xe + e, com e sem interação. No desenvolvimento da metodologia, foram estabelecidas as expressões analíticas correspondentes às hipóteses e somas de quadrados associadas, sobre linhas, colunas e interações, bem como, sobre os métodos computacionais envolvidos nas mesmas. Ainda nesse tópico, foram descritos doze pacotes estatísticos, e suas principais características relativamente a tais hipóteses e somas de quadrados foram apresentadas. Através de exemplo numérico, mostrou-se o desempenho desses pacotes no trato com dados desbalanceados, com algumas caselas vazias, expondo-se suas hipóteses e somas de quadrados associadas; e apresentou-se uma comparação entre os resultados por eles fornecidos.

This article describes the many factors necessary for long-term videotape storage, including a cool, dry environment and proper VTR maintenance. Correct winding techniques are described, detailing tape faults, proper wind tension, and how often the tape should be rewound. Several suggestions are given for measures to prolong the life of videotape, as well as advice on what to do if the tape is exposed to heat or water. A family of constant-moisture curves is given to illustrate the environmental limits of both the tape and the VTR.

Digital composite signals for NTSC and PAL and a single digital component signal are described. User data rates and channel coded rates for a digital videotape recorder are developed for the three types of signals. Methods of error correction for the types of signals are shown and performance results are compared. Continuous standard signals for stop-motion and slow-motion operation of the tape transport are derived and the anticipated performance results are compared.

Technical Briefs Application of Foil Bearing Theory to Vacuum Columns A. Eshel A. Eshel Research Staff, Ampex Corporation, Redwood City, Calif. Search for other works by this author on: This Site PubMed Google Scholar Author and Article Information A. Eshel Research Staff, Ampex Corporation, Redwood City, Calif. J. of Lubrication Tech. Jul 1974, 96(3): 525-526 (2 pages) https://doi.org/10.1115/1.3452034 Published Online: July 1, 1974 Article history Received: January 7, 1974 Online: October 18, 2010

The use of reflecting substrates to enhance the Kerr magnetooptic effect has frequently been discussed. The nature of such a realizable high reflectivity mirror is described in a simple way.