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At least 19 recordsLinked to original sources
PubMed2026

Biologic-biologic and biologic-JAK inhibitor combination therapy in refractory systemic autoinflammatory diseases.

OBJECTIVES: Systemic autoinflammatory diseases (SAIDs) arise from genetic defects in innate immunity, leading to dysregulated activation of inflammatory pathways, including interleukin (IL)-1, IL-6, TNF, and JAK/STAT. Clinical manifestations range from recurrent fever to severe complications such as encephalitis and AA amyloidosis. Management aims to control inflammation using immunosuppressive agents and targeted monotherapies (biologics or JAK inhibitors). Advanced combination therapy (ACT), defined as the use of biologics and/or JAK inhibitors in combination, has emerged as a strategy for refractory disease. METHODS: In this observational retrospective longitudinal cohort study, patients with SAIDs treated with ACT were included. Demographic, clinical, treatment, and safety data were collected. Treatment response was assessed using a composite outcome incorporating corticosteroid dose, C-reactive protein (CRP), and clinical improvement and categorized as non-response, partial response, or complete response. RESULTS: Thirty-eight patients (median age 30 years [range 4-76]) were included. The most common indications for ACT were pyogenic arthritis, pyoderma gangrenosum and acne (PAPA), mevalonate kinase deficiency (MKD), and undifferentiated SAIDs. Most patients had disease-related complications and were dependent on glucocorticoids and/or opioids to control inflammation and pain, respectively. Following multiple ACT trials, complete response was observed in 21 patients (55.3%), partial response in 12 (31.6%), and no response in 5 (13.1%). Overall, 65 ACT regimens were administered, most commonly combining IL-1 and TNF inhibitors. Thirty-nine regimens were discontinued because of lack of efficacy, secondary loss of response, or adverse events. At the final follow-up, 26 patients (68%) remained on ACT, with a median treatment duration of 60 months (range, 11-186). CONCLUSIONS: ACT offers significant clinical benefits for patients with difficult-to-treat SAIDs, though challenges such as secondary loss of efficacy and infection risks remain.

Humans↗
PubMed2026

Biological Parts in Yeast Synthetic Biology: From Regulatory Elements to Predictive Design Platforms.

Yeasts, particularly Saccharomyces cerevisiae, are important eukaryotic chassis for synthetic biology because of their tractable genetics, versatile toolkits, and broad utility in metabolic engineering and functional genomics. Progress in this field has been driven by biological parts that enable programmable control of gene expression and cellular behavior. Early efforts focused mainly on promoters, terminators, and other regulatory elements for tuning individual genes. However, as engineering expanded to multigene pathways, genetic circuits, and dynamic regulatory systems, the limits of part-centric design became clear. Part performance is often shaped by genomic context, chromatin state, host physiology, and interactions with other components, which restricts modularity and predictability. In response, yeast synthetic biology is shifting toward integrated design frameworks combining multilayer regulation, standardized assembly, automated experimentation, and computational modeling. This review provides an integrated perspective on the evolution of biological parts across DNA-, RNA-, and protein-level regulation, connecting these advances with assembly frameworks, biofoundries, and machine learning to trace the trajectory from part-centric engineering toward predictive, system-level design in yeast synthetic biology.

Biofoundry↗
PubMed1979

Physical plasma in biological solids: a possible mechanism for resonant interactions between low intensity microwaves and biological systems.

Observed semiconductor properties of biological material in vitro indicate possible involvement of semiconduction in biological processes. Since in inorganic semiconductors solid-state plasma occurs, it is hypothesized that in organic semiconductors solid-state plasma similarly occurs. Some results of experimental investigation of resonant effects of microwaves in biological systems are considered in the light of that hypothesis. The conditions necessary for the existence of physical plasma in biological solid structures are discussed, and certain parameters of physical plasma in these structures are evaluated. Its is proposed that microwave radiation may support or damp plasma oscillations, thereby stimulating or suppressing biological functions.

Biology↗
PubMed1979

The chemistry and biology of thymosin. I. Isolation, characterization, and biological activities of thymosin alpha1 and polypeptide beta1 from calf thymus.

A partially purified extract from thymus tissue termed thymosin Fraction 5 has been shown to reconstitute immunological deficiencies resulting from the lack of thymic function in several animal models, as well as humans with primary and secondary immunodeficiency diseases. Thymosin Fraction 5 consists of a family of polypeptides with molecular weights ranging from 1,000 to 15,000. Several of these polypeptides contribute individually to the biological activity of the parent compound. Two polypeptide components of thymosin Fraction 5, termed thymosin alpha1 and polypeptide beta1, have been characterized chemically and biologically. Thymosin alpha1 is a highly acidic molecule composed of 28 amino acid residues. This polypeptide has potent biological activity and has been found to be 10 to 1,000 times as active as thymosin Fraction 5 in one in vivo and several in vitro bioassay systems designed to measure differentiation and function of thymus-dependent lymphocytes (T cells). Polypeptide beta1, in contrast, is inactive in our bioassay systems, suggesting that it is not involved in thymic hormone action. Sequence analysis and homology studies have indicated that polypeptide beta1, although present in Fraction 5, does not contribute to the biological activity of thymosin Fraction 5.

Animals↗
PubMed1978

The biology of ethics or the ethics of biology? The biologist's quest for meaning.

The biologist's involvement in value issues concerning the metholology of biological sciences, in establishing the biological basis of ethics and in creating a value system based on biological knowledge is examined. It is proposed that the roots of this involvement are in the conflict of the knowledge-ethic with the established system of values and in the need for metaphysical explanation.

Biology↗
PubMed1977

Biological and immunological characterization of human luteinizing hormone: I. Biological profile in pituitary and plasma samples after electrofocusing.

Pituitary and plasma pools from postmenopausal women and plasma pools from women at midcycle were fractionated by electrofocusing in sucrose density gradients. The biological LH activity was determined in each of the electrofocusing fractions by the use of an in vitro bioassay method. A heterogeneous profile of LH activity was found in both pituitary and plasma samples with a large proportion present within the pH range 6.5-10. In a total of 11 electrofocusing runs 7 main regions of high LH activity were found within this range with mean pI values (+/- SD) of 6.75 +/- 0.08 (n = 6), 7.33 +/- 0.08 (11), 7.80 +/- 0.09 (11), 8.23 +/- 0.10 (11), 8.81 +/- 0.04 (7), 9.17 +/- 0.05 (6) and 9.55 (2). A significantly higher proportion of LH activity was found in the midcycle plasma samples (36%) in the pH regions with mean pI values of 8.81, 9.17 and 9.55 than in postmenopausal plasma (7%) and pituitary extracts (5%). This indicates that the profile of biologically active LH in women in the fertile age is different from that present in postmenopausal women. By detailed fractionation based on narrow pH range studies and the refocusing of specific peak fractions it was shown that each of the regions studied consisted of several peaks of LH activity indicating the presence of a large number of molecular species exhibiting varying degrees of LH activity. The relative proportions of these species showed considerable differences between sources but also between samples from the same source.

Animals↗
PubMed1979

Lipophilicity and biological acitivity. Drug transport and drug distribution in model systems and in biological systems.

Different equilibrium and non-equilibrium models are used to simulate drug transport and drug distribution. The percentage of absorbed drug, the rate constants of drug absorption and the drug concentrations in the different compartments of the models can be described quantitatively by the bilinear model, e.g., log ci = a log P-b log (betaP + 1) + c. A nearly perfect fit is obtained for the simulated data from this model. Drug absorption and distribution in biological systems can be explained and described by the model-derived equations. Examples from the literature include buccal absorption, gastric and intestinal in situ and in vitro absorption, colonic absorption, renal clearance, and absorption through the skin and the blood-brain barrier; in all those cases the bilinear model gives an excellent fit of the experimental data. Combination of the pH-partition theory with the bilinear model leads to a simple quantitative model for the precise description of the relationships between lipophilicity, degree of ionization, and absorption, distribution and biological activity of drugs.

Absorption↗
PubMed1976

Synthesis of biologically active spin-labelled radioactive cytidine diphosphodiglyceride, a novel probe for biological membranes.

A versatile synthesis of spin-labelled radioactive cytidine diphospho-sn-1,2-diacylglycerol (CDP-diglyceride) has been developed based on the combination of the enzymatic acylation of radioactive sn-glycero-3-phosphate with 12-doxyl stearic acid and the chemical conversion of the thus obtained spin-labelled radioactive phosphatidic acid with cytidine monophosphomorpholi-date into spin-labelled radioactive CDP-diglyceride. The method for the isolation and purification of the latter compound was described. This obtained CDP-[2-3H]diglyceride contained 10% of fatty acids of paramagnetic nature, presumably present as a covalently bound 12-doxyl stearic acid esters. The biological activity was tested by using the synthesized compound as a substrate in the mitochondrial biosynthesis of phosphatidylglycerol. It was found that spin-labelled CDP-[2-3H]diglyceride prepared as described can be converted in the presence of sn-[2-14C]-glycero-3-phosphate into a spin-labelled [2-3H, 2'-14C]phosphatidylglycerol with isolated rat liver mitochondria, establishing therefore that the site of its utilization is identical with the site of phosphatidylglycerol synthesis in isolated mitochondria, i.e. inner mitochondrial membrane. Results described demonstrate that the synthesized spin-labelled CDP-diglyceride can be used as a specific probe for the spin- and radioactive covalent labelling of polyglycerophosphatides of mitochondrial membranes. Some implications and further possibilities in the study of biological membranes using the spin-labelled radioactive CDP-diglyceride are discussed.

Animals↗
PubMed1976

Biological ion exchanger resins. X. The cytotonus hypothesis: biological contractility and the total regulation of cellular physiology through quantitative control of cell water.

Actin-like (A-L) fraction from normal E. coli was compared with the protein from a potassium-transport mutant strain, and the cell-swelling reaction of both strains was studied. Findings were: (a) The membrane fraction of the mutant by SDS electrophoresis is deficient in the A-L fragment relative to normal whereas the soluble supernatant contains an excess. (b) Important catalytic differences exist between the A-L fractions of the two strains. The parent strain accumulates potassium in low K+ and the A-L fraction polymerizes in low K+. But the A-L fraction from the mutant fails to polymerize in low K media in the K+ concentration region where the mutant fails at K+ uptake. (c) The parent cell swells during low K+ uptake whereas the mutant does not. It is constructed from this that the differences in the characterization of A-L fraction relative to normal are related to the loss of cell-swelling in the mutant and hence to the loss in alkali cation selectivity. Thus two physical mechanisms, one macroscopic and dependent on the Gregor relation for swelling equilibria in ion exchange resins, and one more microscopic based on the dielectric dependence of the coulomb force between ion pairs, could underly regulation of ion selectivity by cell swelling. A similar proposal is made for the regulation of electron transport and oxidative phosphorylation in mitochondria. These findings and interpretations justify a new hypothesis to the effect that cell hydration is regulated by contractile proteins. The hypothesis fits together important observations hitherto unexplained, to wit: (1) The "missing link" as to the role of intermediate metabolism in biological ion exchange. (2) The swelling of bacterial protoplasts and its relation to (Mg2 + Ca2+)ATPase activity. (3) The swelling-contraction cycles of mitochondria and their role in electron transport. (4) The role of ATPase's in transport. (5) The significance of actomyosin fibers in nerve endings. (6) The significance of altered actomyosin structures in the cancerous cell.

Actins↗
PubMed1978

Preparation of biological material for X-ray microanalysis of diffusible elements. I. Rapid freezing of biological tissue in nitrogen slush and preparation of ultrathin frozen sections in the absence of trough liquid.

Any method used for the analysis of diffusible elements within a cell should involve conditions which eliminate the redistribution of those elements. Redistribution of diffusible substances is caused by (a) ice damage during freezing, (b) thawing during sectioning, and (c) thawing during handling of sections. To eliminate this sections were cut (a) in the 5-8 micrometer ice crystal free surface layer obtained by freezing in melting nitrogen, (b) at a specimen temperature of 133 K and a knife temperature of 173 K to 153 K, and the temperature of the chamber was kept low by evaporating nitrogen from an extra reservoir inside the chamber, by regulating the output of a foil heater. A grid carrier was designed to simplify the section collection and the sections were affixed on to the grid in a press assembly. The sections were hard and translucent, and showed faint interference colours.

Adipose Tissue, Brown↗