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At least 73 records · Page 4Linked to original sources
PubMed2026

Programmed cell death and risk of diabetic retinopathy: a Mendelian randomization study.

BACKGROUND: Programmed cell death (PCD) plays an important role in diabetic retinopathy (DR); however, the underlying genetic mechanisms remain unclear. We used Mendelian randomization (MR) to investigate the causal relationships between PCD-related genes and DR. This study aimed to investigate the effects of PCD on the risk of DR by conducting MR analysis. METHODS: Summary statistics from gene expression quantitative trait loci (eQTL) studies (31,684 Europeans) were analyzed. Genetic instrumental variables were selected using cis-eQTL single-nucleotide polymorphisms (SNPs; P&#x2009;<&#x2009;5&#x2009;&#xd7;&#x2009;10-&#x2009;8). Summary data-based MR (SMR) was employed to assess causal associations between PCD-related genes and DR, with three additional MR methods used for sensitivity testing. Bayesian colocalization was used to examine the shared regulatory mechanisms between PCD QTLs and DR risk loci. RESULTS: Sensitivity and colocalization analyses revealed six genes that affected DR: cathepsin H (CTSH), NAD(P)H: quinone oxidoreductase 1 (NQO1), tribbles pseudokinase 3 (TRIB3), and phosphoglycerate mutase 5 (PGAM5), which increased DR risk, and iron-responsive element binding protein 2 (IREB2) and tumor necrosis factor (TNF), which exhibited protective effects. Multivariate MR confirmed significant causal effects for CTSH, IREB2, and PGAM5 (p&#x2009;<&#x2009;0.050). Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis (including 10 STRING-derived genes) revealed that 13 genes were enriched in necroptosis, apoptosis, mitophagy, and TNF signaling pathways in DR. CONCLUSIONS: This MR study supports the causal involvement of PCD in DR and identifies candidate genes (CTSH, IREB2, PGAM5, NQO1, TRIB3, and TNF) for therapeutic targeting or biomarker development in DR prevention or diagnosis.

Humans↗
PubMed1979

Interactions of band 3-protein from human erythrocyte membranes with cholesterol and cholesterol analogues.

The interaction between cholesterol and band 3-protein from human erythrocyte membranes was studied by incorporating the solubilized protein into monolayers of cholesterol and related sterols at the air-water interface and measuring the changes in surface pressure which accompanied protein incorporation. The following results were obtained: 1) Band 3-protein shows a very strong interaction with cholesterol monolayers. Both apolar and polar bonds contribute to this interaction. 2) Steroids with a structure slightly different from that of cholesterol (especially with respect to the polar group and the side chain) in most cases show a reduced affinity for band 3-protein. Thus, the protein-sterol interaction is highly specific. It is assumed that the protein-cholesterol interaction can be subidivided into two parts: an unspecific one which results from contributions from several sterol molecules, and a specific one which is due to the high affinity binding of the protein and cholesterol. The structural element responsible for the high affinity interaction is assumed to be a sterol-binding niche on the surface of band 3-protein. The sterol is thought to be held in the niche by a hydrogen bond at its polar head and a variety of hydrophobic bonds along its ring system and side chain.

Cholesterol↗
PubMed2026

Molecular determinants of AR-enhancer interaction and cistrome reprogramming in prostate cancer progression.

The androgen receptor (AR) is a key transcription factor in prostate cancer (PCa), whose enhanced and altered functions are known drivers of cancer progression. A key aspect of this is reprogramming of the AR cistrome, which consists of genome-wide enhancer-binding sites through which AR regulates gene expression. The magnitude and biological impact of the AR cistrome are impacted by the AR itself, including the responses to ligand, as well as the organization of the associated DNA response elements, and availability of pioneer factors, cofactors, and noncoding RNAs, all of which contribute to a functional transcription complex. In this review, we will examine, in the context of PCa progression, the factors that affect the binding of AR and its interacting partners at enhancers, with a focus on AR cistrome reprogramming. We also discuss the clinical utility of targeting the AR-enhancer nucleoprotein complex and the potential of using the AR cistrome as a prognostic tool.

Humans↗
PubMed2026

Defining the potential role of the mineralocorticoid receptor in musculoskeletal health and bone crosstalk with other tissues.

Excessive mineralocorticoid receptor (MR) activation in the heart and vasculature leads to pathological effects such as extracellular matrix accumulation, oxidative stress, and sustained inflammation. While MR's role in cardiovascular and renal systems is well understood, MR signaling has also been implicated as a key driver of homeostasis and pathological changes in several other body systems, including skeletal muscle and adipose tissue. The glucocorticoid receptor (GR) and MR are structurally and functionally linked, sharing 95% similarity in DNA-binding domains and recognizing many of the same hormone response elements (HREs) as transcriptional regulators of target genes. The role of GR in bone has been defined through several mechanistic studies, whereas the role of MR in bone is understudied. Because mineralocorticoid signaling regulates renal sodium and calcium handling, chronic hyperaldosteronism may indirectly disrupt skeletal homeostasis through urinary calcium wasting and secondary alterations in parathyroid hormone signaling. Furthermore, MR inhibition through MR antagonists (MRAs) has been associated with beneficial skeletal effects, particularly in settings of hyperaldosteronism and 11&#x3b2;-HSD2 deficiency. In this review, we present historical and current scientific findings on the role of genomic MR signaling in bone and extra-skeletal tissues that may be involved in crosstalk with the skeletal system. Furthermore, we also highlight the availability of tools to study MR signaling in the context of the musculoskeletal system.

Humans↗
PubMedDate not supplied

[Design and production problems with stethophonoendoscopes].

The existing stethophonendoscope models with separate stethoscopic and phonendoscopic heads fail to give adequate reproduction of processes under investigation within the auscultation frequency range with intensity sufficient for reliable diagnosis. The Leningrad industrial association "Krasnogvardeets" offers a new stethophonendoscope design with a head reproducing acoustic signs at a necessary intensity level within a wide frequency range. These stethophonendoscopes can be manufactured serially because their most complicated and functionally responsible elements are strictly unified for different models.

Auscultation↗
PubMed1977

[Cytoplasmic microfilaments in laryngeal carcinoma malignant keratinocytes (author's transl)].

The fine structure of malignant keratinocytes of invasive squamous cell carcinoma of the human larynx was studied by electron microscopy. In these malignant cells a system organized 50--70 A microfilaments is prominent in the cortical cytoplasm of the lateral and basal cell surfaces. The microfilaments are arranged either in oriented bundles or form a complex filamentous network. The bundles may lie parallel to the plasma membrane and to the long axis of the cell. The microfilaments are situated at the base of the pseudopodia-like cell processes or are found extending into microvillous cytoplasmic extensions. In some places the bundles are some associated with the plasmalemma displaying electron-dense attachment sites. Desmosomes or other types of junctional complexes invariably remain free of microfilaments. At higher magnification the individual microfilaments are seen to be interconnected transversely by a polygonal interfilamentous meshwork. Within the bundles of microfilaments focal regions of increased electron density, similar to the Z-band of sarcomeres, are observed. Organized bundles of oriented 50--70 A microfilaments do not occur in normal squamous epithelial cells of laryngeal mucosa. By analogy with various motile microfilament containing cell systems which have been shown biochemically to contain the contractile protein actin, these cytoplasmic microfilaments may be the structural elements responsible for the migratory invasive properties of malignant keratinocytes in cancer of the larynx.

Biopsy↗
PubMed1976

[Mechanism of action of drugs currently used in the prevention of migraine].

The mode of action of some classical and newer drugs used in the preventive interval treatment of migraine is discussed in the light of a modern theory of the pathogenesis of migraine headache. This headache is produced when two elements--a passive distension of the extracranial arteries and a lowering of the pain threshold of the receptors situated in the walls of the affected vessels--are present simultaneously. The main humoral factors involved in this phenomenon are plasma-kinins, serotonin and--to a lesser degree--histamine. The role played by serotonin which is released by the blood platelets at the onset of the attack is twofold: on the one hand, free serotonin increases the permeability of the capillaries, favouring transudation of plasmakinins, and lowers the pain threshold, while on the other hand, its increased excretion causes a secondary reduction in its plasma concentration, promoting hypotonicity of the extracranial vessels. Among the substances used for prophylactic interval treatment, some, such as dihydroergotamine, clonidine and the beta-blocking agents have a purely vascular site of action, maintaining--by various mechanisms--the tone of the extracranial arteries and thus reducing their lability. Methysergide and pizotifene have a chiefly indirect effect on the vessels, by potentiating the effect of catecholamines or helping to maintain free serotonin at a certain level. They act primarily against the humoral elements responsible for lowering the pain threshold: methysergide by inhibiting the release and blocking the effects of serotonin, by countering the potentiating effect of serotonin on the pain induced by plasmakinins and by inhibiting histamine release; pizotifene by inhibiting the release and blocking the effects of histamine, by blocking the effects of serotonin and by slightly inhibiting the peripheral effects of plasmakinins. Thus, the multifactorial pathogenesis of migraine helps to explain the effectiveness against migraine of substances possessing the most varied pharmacodynamic profiles.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

[Preschool age mortality (1-4-year olds) in Cuba, 1961-1975].

An abstract is made of the preschool age mortality in Cuba through the period of 1961 to 1975. The authors outlight how it has dropped from 2.0 to 1.1 per 1000 population to reach 45% reduction. They establish comparison with a group of American countries, setting of contrast with the low mortality in Cuba. The mortality in children of 1 to 4 years old is considered as indirect index of malnutrition. The percentage of diminution for the different departments in the period stated is as follows: Pinar del Río, 57.6%; Havana, 43.7%; Matanzas, 58.5%; Las Villas, 63.1%; Camagüey, 50.0%; Oriente, 39.0%. The 10 most important causes of death are analyzed and the percentages in drop of mortality are reported as follows: (A 43), 80.0%; (A65) and (A105-106), 66.7%; (A5), 61.5%; (A93), 50.0%; (A89, 90, 91 and 92), 46.5%; (A21), 42.8%; (AE 138-146), 34.6%; (A126-130), 31.2%; (A25), 25.0%. Finally, stress is placed on the elements responsible for the drop in preschool age children's mortality.

Child, Preschool↗
PubMed1976

Pancreatic enzyme response with an elemental diet.

Elemental diets can maintain or slightly improve the nutritional status without a major stimulatory effect on the pancreas. Six dogs were maintained with a regular chow diet, switched to an elemental diet and, subsequently, returned to a chow diet. Cannulation of the pancreatic duct through a duodenal cutaneous fistula revealed the enzyme response to be decreased in a dog maintained with an elemental diet, with no or only a slight weight gain. Return to a regular diet resulted in a return of pancreatic enzyme response.

Amino Acids↗
PubMed2025

Post-translational modifications of the nucleoid protein H-NS: sites, mechanisms, and regulatory cues.

Histone-like nucleoid structuring protein H-NS plays a pivotal role in orchestrating bacterial chromatin and regulating horizontal gene transfer (HGT) elements. In response to environmental signals, H-NS undergoes dynamic post-translational modifications (PTMs) that resemble the epigenetic codes of eukaryotic histones. This review explores how environmental cues regulate PTMs at specific sites within distinct domains of H-NS, thereby modulating its oligomerization and DNA-binding capabilities to reprogram bacterial responses. Notably, HGT elements commonly encode counter-silencing factors, including PTM-modifying enzymes, that counteract H-NS repression. We propose that combinatorial PTM patterns on H-NS form the bacterial histone-like epigenetic code, regulating the expression of HGT elements. Collectively, these interactions establish a sophisticated network of silencing and counter-silencing mechanisms that drive bacterial genome evolution.

Protein Processing, Post-Translational↗
PubMed1977

The electrolytic conductivity detector as an element-selective gas chromatographic detector.

The response and elemental selectivity of the electrolytic conductivity detector (E1CD) to nitrogen-, chlorine-, and sulfur-containing compounds has been investigated as a function of chemical structure, furnace chemistry conditions (i.e., reaction gas, furnace temperature, catalyst, and post-furnace chemical abstractors), and solubilization-and-ionization processes (electrolytic chemistry and electrolytic conductance). The "profiling" of detector response for the gas-liquid chromatographic-E1CD analysis of selected compounds under defined furnace chemistry reaction conditions and electrolytic chemistry included the determination of detector signal to noise ratio, peak tailing, and elemental selectivity. Detector response and conductivity phenomena are discussed in terms of gas-phase furnace chemistry reactions, post-furnace reaction or abstraction processes, and solution-phase ionization and neutralization processes occurring in the conductivity cell.

Antidepressive Agents↗
PubMed2026

Genome-wide identification of the superoxide dismutase gene family in Lycium barbarum and their expression profiles under abiotic stress and phytohormone treatment.

BACKGROUND: Superoxide dismutases (SODs) are crucial metalloenzymes that constitute the first line of defense against reactive oxygen species in plants under abiotic stress. Wolfberry (Lycium barbarum) is an economically important medicinal plant with notable stress tolerance, however, a comprehensive genome-wide analysis of its SOD gene family has not yet been performed. RESULTS: We identified ten wolfberry SOD genes (LbaSODs) and classified them into three subfamilies: iron-SODs (Fe-SODs), manganese-SODs (Mn-SODs), and copper/zinc-SODs (Cu/Zn-SODs). Members within each subfamily shared conserved gene structures and motifs. Segmental duplication was the primary driver of LbaSOD expansion, with three paralogous pairs identified. Analysis of cis-regulatory elements in the promoter region revealed a predominance of stress- and hormone-responsive cis-elements, particularly ABA-responsive elements (ABREs) (22 copies) and LTR (17 copies) motifs. Tissue-specific expression profiling revealed that LbaSOD2 and LbaSOD5 expression peaked during early fruit development, whereas LbaSOD6, LbaSOD9, and LbaSOD10 were progressively upregulated through fruit maturation. Under abiotic conditions, Fe-SOD members were markedly suppressed during prolonged drought, whereas LbaSOD9 and LbaSOD10 were rapidly induced in response to salt stress. Among the phytohormone treatments, methyl jasmonate (MeJA) elicited the most pronounced response, with LbaSOD5 expression increasing by approximately 60-fold after 24 hours. Notably, abscisic acid (ABA) triggered an exceptionally strong transcriptional induction of LbaSOD5 (2.5 &#xd7; 105-fold), LbaSOD10 (6 &#xd7; 105-fold), and LbaSOD6 (70-fold). In addition, LbaSOD3 and LbaSOD7 transcripts were undetectable in any of the tested conditions. CONCLUSIONS: This study provides the first comprehensive characterization of the LbaSOD gene family and elucidates its hormone- and stress-responsive regulatory landscape, providing a valuable foundation for future functional investigations of LbaSOD genes in abiotic stress adaptation. The extraordinarily strong ABA-mediated induction of specific LbaSOD members, together with their tissue- and stress-specific expression patterns, highlights their potential as targets for genetic improvement of stress tolerance in wolfberry.

Lycium barbarum↗
PubMed2026

Genome-wide identification and cold-stress-responsive expression analysis of the NOX gene family in Cucumis melo.

NADPH oxidases (NOXs) are crucial enzymes for reactive oxygen species (ROS) generation in plants and play vital roles in growth, development, and stress responses. To elucidate the sequence characteristics of the NOX gene family and its low-temperature response patterns in melon (Cucumis melo L.), this study conducted genome-wide identification and expression profiling of NOX family members using bioinformatics analysis, RNA-seq transcriptome sequencing, and real-time quantitative PCR (RT-qPCR). The results revealed that eight NOX members were identified in the melon genome, distributed across six chromosomes. All members harbored conserved domains including Ferric_reductase, FAD_binding_8, NAD_binding_6, and NADPH_Ox, and the encoded proteins were generally basic and hydrophilic. Phylogenetic analysis classified the NOX proteins into five subgroups. Synteny analysis indicated the presence of only one pair of intraspecific duplicated genes in melon, which was under purifying selection. The promoter regions contained multiple hormone- and stress-responsive cis-acting elements, with CmNOX2 and CmNOX4 harboring low-temperature responsive elements. Following treatment at 4&#x2103; for 24 h and 48 h, leaf relative electrolyte leakage (REL) increased from 28.33% to 42.67% and 52.67%, respectively; transcriptome analysis identified 5,633 and 6,882 differentially expressed genes (DEGs), respectively. Cold-responsive genes exhibited significant differential expression, with SLAC1 and CPK19 showing sustained upregulation. RT-qPCR results demonstrated that the expression of CmNOX2, CmNOX5, CmNOX6, and CmNOX7 was significantly downregulated after low-temperature treatment, whereas CmNOX4 expression was significantly upregulated at 48 h. Integrating promoter elements and expression characteristics, CmNOX4 may represent an important candidate gene involved in melon low-temperature response. This study systematically characterized the structure, evolution, and expression patterns of the melon NOX gene family, identified candidate genes responsive to low temperature, and provides a reference for further investigation into the mechanisms underlying melon cold adaptation.

Cucumis melo↗
PubMed1977

The effect of the spacing of background elements upon optomotor memory responses in the crab: the influence of adding or deleting features during darkness.

1. Study was made of the effect of separation between stripes in the visual field upon responses which indicate memory of those stripes. 2. The amount of separation between white stripes had very little effect, whereas response strength and the amount of separation between black stripes were directly proportional. 3. The presence of extra, non-displaced black stripes prior to or following displacement reduced the size of the memory responses. 4. The effects of the amount of separation in the two cases were comparable. In both situations the separation affected only the responses to displacement of the stripe borders nearest to the extra stripe. 5. The effect of extra stripes present prior to displacement was in turn affected by the duration of the dark period, whilst the effect of those present during the post-displacement period was not. This accounts for the larger effect of extra stripes present during the psot-displacement period. 6. By expanding stripe width during darkness it was possible to distinguish between the effects of distance between stripes and the amount of white space separating them. Reducing white space while distance remains constant causes reductions in response strength, whereas reducing the distance between a memory zone and the white space between it and the neighboring stripe increased the size of the memory response.

Action Potentials↗
PubMed2026

Genome-wide AP2/ERF analysis identifies HmaERF87 as a positive regulator of Hydrangea macrophylla leaf spot resistance.

A total of 164 APETALA2/ethylene-responsive factor (AP2/ERF) genes were identified in Hydrangea macrophylla, and HmaERF87 positively contributes to leaf spot resistance. The APETALA2/ethylene-responsive factor (AP2/ERF) transcription factor family plays important roles in plant stress responses, but its contribution to disease resistance in Hydrangea macrophylla (hydrangea) remains poorly understood. In this study, 164 AP2/ERF genes were identified in the H. macrophylla genome and classified into APETALA2 (AP2), ethylene-responsive factor (ERF), dehydration-responsive element-binding (DREB), and related to ABI3/VP1 (RAV) subfamilies. Their chromosomal distribution, conserved motifs, gene structures, and duplication patterns were analyzed. A total of 46 pathogen-responsive H. macrophylla AP2/ERF (HmaERF) genes were identified from the RNA sequencing (RNA-seq) dataset of resistant and susceptible cultivar leaves collected before and after Corynespora cassiicola inoculation. Promoter analysis revealed that the HmaERF genes with upregulated expression post-C. cassiicola infection showed a higher frequency and copy number of jasmonate-responsive cis-regulatory elements, suggesting their possible involvement in hormone-mediated defense responses. Three infection-induced candidate genes, including HmaERF56, HmaERF87, and HmaERF129, were selected for functional validation using virus-induced gene silencing (VIGS) in hydrangea leaf discs. Silencing of HmaERF87 expression via VIGS significantly increased lesion development after C. cassiicola inoculation, whereas the transient overexpression of HmaERF87 reduced the area of leaf disc lesions. Subcellular localization showed that the HmaERF87 protein was localized in the nucleus, and yeast assays indicated that its transcriptional activation activity was mainly associated with the C-terminal region of the protein. These results support a role for HmaERF87 as a positive regulator of H. macrophylla resistance to leaf spot disease and provide a candidate gene for further studies of disease resistance in hydrangea.

Plant Proteins↗
PubMed1978

Effect of continuous jejunal perfusion of elemental and complex nutritional solutions on pancreatic enzyme secretion in human subjects.

Pancreatic secretion of lipase and chymotrypsin in response to elemental diets and a crushed food homogenate was studied in normal subjects. The solutions were infused at constant flow rates at the ligament of Treitz with polyethylene glycol as a nonabsorbable marker. A triple lumen tube was used, enabling collection of secretions at 35 and 70 cm from the infusion point. The results show that a crushed food homogenate has a greater stimulative effect on pancreatic enzyme secretion than the elemental solutions and that this can be directly related to its greater nitrogen content. The osmolality of the infused solutions does not appear to be important. The relative merits of the solutions tested and total parental nutrition in reducing pancreatic enzyme secretion are discussed.

Adolescent↗
PubMed1979

Radiopaque zones in the dentin beneath silicate fillings analyzed by electron microprobe.

Seven teeth which showed radiopaque zones beneath silicate fillings were sectioned and studied by microradiography and electron microprobe analysis in order to elucidate which elements were responsible for the increased absorption of X-rays and whether the presence of carious lesions could be masked by foreign elements in the tissue. The Ca concentration was frequently found to be either slightly increased or reduced compared with radiographically unaltered dentin. Increased concentrations of F and Zn occurred in the radiopaque zones. The highest F concentrations (0.4--1%) were recorded in zones with an increased Ca content. The highest Zn concentrations (5--8%) were found in the three specimens having a reduced Ca content. The possible conditions responsible for the increased Ca, F and Zn concentrations are discussed. The results indicate that both Ca and Zn may contribute to the increased absorption of X-rays. The hypothesis that carious dentin may be obscured in intraoral radiographs by the presence of foreign elements in the tissue, was not substantiated.

Calcium↗