Dynamic Physiological Processes Research Articles

Visualizing DNA/RNA, Proteins, and Small Molecule Metabolites within Live Cells.

Live cell imaging is essential for obtaining spatial and temporal insights into dynamic molecular events within heterogeneous individual cells, in situ intracellular networks, and in vivo organisms. Molecular tracking in live cells is also a critical and general requirement for studying dynamic physiological processes in cell biology, cancer, developmental biology, and neuroscience. Alongside this context, this review provides a comprehensive overview of recent research progress in live-cell imaging of RNAs, DNAs, proteins, and small-molecule metabolites, as well as their applications in molecular diagnosis, immunodiagnosis, and biochemical diagnosis. A series of advanced live-cell imaging techniques have been introduced and summarized, including high-precision live-cell imaging, high-resolution imaging, low-abundance imaging, multidimensional imaging, multipath imaging, rapid imaging, and computationally driven live-cell imaging methods, all of which offer valuable insights for disease prevention, diagnosis, and treatment. This review article also addresses the current challenges, potential solutions, and future development prospects in this field.

Changes in protein fluxes in skeletal muscle during sequential stages of muscle regeneration after acute injury in male mice

Changes in protein turnover play an important role in dynamic physiological processes, including skeletal muscle regeneration, which occurs as an essential part of tissue repair after injury. The inability of muscle tissue to recapitulate this regenerative process can lead to the manifestation of clinical symptoms in various musculoskeletal diseases, including muscular dystrophies and pathological atrophy. Here, we employed a workflow that couples deuterated water (2H2O) administration with mass spectrometry (MS) to systematically measure in-vivo protein turnover rates across the muscle proteome in 8-week-old male C57BL6/J mice. We compared the turnover kinetics of over 100 proteins in response to cardiotoxin (CTX) induced muscle damage and regeneration at unique sequential stages along the regeneration timeline. This analysis is compared to gene expression data from mRNA-sequencing (mRNA-seq) from the same tissue. The data reveals quantitative protein flux signatures in response to necrotic damage, in addition to sequential differences in cell proliferation, energy metabolism, and contractile gene expression. Interestingly, the mRNA changes correlated poorly with changes in protein synthesis rates, consistent with post-transcriptional control mechanisms. In summary, the experiments described here reveal the signatures and timing of protein flux changes during skeletal muscle regeneration, as well as the inability of mRNA expression measurements to reveal changes in directly measured protein turnover rates. The results of this work described here provide a better understanding of the muscle regeneration process and could help to identify potential biomarkers or therapeutic targets.

WITHDRAWN: Transdifferentiation of Human Neonatal Foreskin Fibroblasts into Keratinocyte-like Cells via Regulating the AKT/P53/WNT/LEF1 Axis

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Topical gel preparation from Staphylococcus epidermidis isolate extract accelerated healing on incision wound model in rats

A wound is a disorder of skin integrity caused by physical trauma or disease. Wound healing is a natural restorative response to tissue injury. It is a complex dynamic physiological process involving several overlapping phases. Although wound management has been applied, however, some time it is associated withmajor drawbak including invasiveness, antibiotic resistance, and high costs. Natural medicines are being developed for wound management to resolve the drawback. Commensal Staphylococcus epidermidis was proven to play a role in natural wound healing process. This study aimed to investigate the wound healingactivity of a topical gel preparation containing S. epidermidis isolate extract on an incision wound model in rats. The methanol extract of S. epidermidis isolate was prepared by maceration and used as an active ingredient of the topical gel using NaCMC as a gelling agent. A physical stability test was carried out by assessingorganoleptic properties, pH value, homogeneity, dispersion, and viscosity of the gel preparation. The gel preparation was then topically applied once-daily for 11 d on incision wound model of male white rats (Rattus norvegicus). The wound healing was observed daily and calculated using Morton’s formula. Nosignificant change in the physical stability parameters of the gel preparation was observed during observation on day 1, 7, and 14 (p>0.05). A significant increase in wound healing after the application of the gel preparation compared to negative control was observed (p<0.05). In contrast, no significant difference inwound healing between the gel preparation and the positive control group was observed (p>0.05). In conclusion, the topical gel preparation from S. epidermidis isolate extract accelerates healing on incision wound models in rats.

Abstract 4473: Targeting matrix metalloproteinase-3 (MMP-3) in high-grade serous ovarian cancer

Abstract High-Grade Serous Ovarian Cancer (HGSOC) is the most aggressive and lethal gynecological malignancy. Surgery and chemotherapy (with platinum compounds) are the main treatments. Many patients relapse and develop chemotherapy resistance, limiting the therapeutic utility of these therapies. This persistent resistance makes HGSOC treatment difficult. Cisplatin-resistant ovarian cancer cells upregulate Matrix Metalloproteinase-3. MMP3 is an enzyme involved in active tissue remodeling and extracellular matrix protein breakdown during dynamic physiological processes. The structure of MMP3 includes the prodomain, the catalytic domain and the hemopexin domain. We showed that MMP3 protein levels are higher in cisplatin resistant as compared with cisplatin sensitive HGSOC cells. Our research team showed that small interference RNA (siRNA)-mediated MMP3 knockdown reduced cisplatin-resistant ovarian cancer cell growth and invasion. This data indicates that MMP3 may be a promising HGSOC treatment target. Targeting MMP3 with small chemical inhibitors (SCI) could represent a better option than siRNA because SCI are more stable and easier to deliver. The purpose of this project is to design SCI of MMP3 in the propeptide, catalytic, and hemopexin domains of MMP3. We used in silico methods to identify MMP3 inhibitors in these domains. The ZINC20 database of commercially compounds was used for virtual screening using Python Prescription (PyRx) software. We identified 25 ligands out of 370,000 with the greatest affinity for each MMP3 functional domains. SwissADME was then used to evaluate in silico absorption, distribution, metabolism, pharmacokinetics, drug-likeliness, and medicinal chemistry. This research lays the groundwork for HGSOC therapeutic strategies to improve treatment efficacy, especially for chemotherapy-resistant patients. Citation Format: Víctor G. Reyes-Burgos, Eliud Hernández-O'Farrill, Luis E. Vazquez Quiñones, Marienid Flores-Colón, Fatima Valiyeva, Pablo E. Vivas-Mejía. Targeting matrix metalloproteinase-3 (MMP-3) in high-grade serous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4473.

Perfluorinated Iridium Catalyst for Signal Amplification by Reversible Exchange Provides Metal-Free Aqueous Hyperpolarized [1-13C]-Pyruvate.

Hyperpolarized (HP) carbon-13 [13C] enables the specific investigation of dynamic metabolic and physiologic processes via in vivo MRI-based molecular imaging. As the leading HP metabolic agent, [1-13C]pyruvate plays a pivotal role due to its rapid tissue uptake and central role in cellular energetics. Dissolution dynamic nuclear polarization (d-DNP) is considered the gold standard method for the production of HP metabolic probes; however, development of a faster, less expensive technique could accelerate the translation of metabolic imaging via HP MRI to routine clinical use. Signal Amplification by Reversible Exchange in SHield Enabled Alignment Transfer (SABRE-SHEATH) achieves rapid hyperpolarization by using parahydrogen (p-H2) as the source of nuclear spin order. Currently, SABRE is clinically limited due to the toxicity of the iridium catalyst, which is crucial to the SABRE process. To mitigate Ir contamination, we introduce a novel iteration of the SABRE catalyst, incorporating bis(polyfluoroalkylated) imidazolium salts. This novel perfluorinated SABRE catalyst retained polarization properties while exhibiting an enhanced hydrophobicity. This modification allows the easy removal of the perfluorinated SABRE catalyst from HP [1-13C]-pyruvate after polarization in an aqueous solution, using the ReD-SABRE protocol. The residual Ir content after removal was measured via ICP-MS at 177 ppb, which is the lowest reported to date for pyruvate and is sufficiently safe for use in clinical investigations. Further improvement is anticipated once automated processes for delivery and recovery are initiated. SABRE-SHEATH using the perfluorinated SABRE catalyst can become an attractive low-cost alternative to d-DNP to prepare biocompatible HP [1-13C]-pyruvate formulations for in vivo applications in next-generation molecular imaging modalities.

Безклітинні біологічні засоби: нові горизонти у лікуванні передчасно народжених дітей (огляд літератури)

Preterm birth, is a complex syndrome and remains a major global health problem. Taking into account the plasticity and regenerative potential of developing organs, nowadays the most promising therapeutic strategy is the use of mesenchymal stem cells (MSCs) and their derivatives. Aim. To summarize current information about the therapeutic potential of cell-free biological agents in the treatment of diseases of premature newborns according to data from open sources of information. Publications have been selected, which covered information on the use of conditioned media and MSC exosomes in the treatment of diseases of premature newborns. In comparison to MSCs, the use of cell-free agents has advantages: the use of the secretome eliminates the risks potentially associated with the transplantation of living and proliferative cell populations, including immune compatibility, tumorigenicity, emboli formation, and transmission of infections; MSC-derived secretome can be evaluated for safety, dosage, and efficacy in a manner similar to conventional pharmaceutical agents; storage can be carried out without the use of potentially toxic cryopreservatives for a long period without losing the effectiveness of the product; the use of secretome from MSCs, such as conditioned MSC medium, is more economical and more practical for clinical use, as it avoids invasive cell collection procedures; mass production is possible using custom-made cell lines in controlled laboratory conditions, providing a convenient source of bioactive factors; the time and cost of expansion and maintenance cultured stem cells could be greatly reduced, and ready-made secretome therapies could be immediately available for the treatment of acute conditions; a biological product obtained for therapeutic use can be modified to have the desired cell-specific effects. Conclusions. The treatment of premature newborns represents a unique clinical task, since their diseases involve dynamic physiological processes in immature, developing organs. The introduction into clinical use of cell-free biological agents is one of the most promising areas in the development of neonatology and will obviously change the paradigms in the treatment of a number of diseases of newborns, in particular bronchopulmonary dysplasia, hypoxic ischemic encephalopathy and necrotizing enterocolitis. No conflict of interests was declared by the authors.

Graphene enhances artemisinin production in the traditional medicinal plant Artemisia annua via dynamic physiological processes and miRNA regulation

We investigated the effects of graphene on the model herb Artemisia annua, which is renowned for producing artemisinin, a widely used pharmacological compound. Seedling growth and biomass were promoted when A. annua was cultivated with low concentrations of graphene, an effect which was attributed to a 1.4-fold increase in nitrogen uptake, a 15%–22% increase in chlorophyll fluorescence, and greater abundance of carbon cycling–related bacteria. Exposure to 10 or 20 mg/L graphene resulted in a ∼60% increase in H2O2, and graphene could act as a catalyst accelerator, leading to a 9-fold increase in catalase (CAT) activity in vitro and thereby maintaining reactive oxygen species (ROS) homeostasis. Importantly, graphene exposure led to an 80% increase in the density of glandular secreting trichomes (GSTs), in which artemisinin is biosynthesized and stored. This contributed to a 5% increase in artemisinin content in mature leaves. Interestingly, expression of miR828 was reduced by both graphene and H2O2 treatments, resulting in induction of its target gene AaMYB17, a positive regulator of GST initiation. Subsequent molecular and genetic assays showed that graphene-induced H2O2 inhibits micro-RNA (miRNA) biogenesis through Dicers and regulates the miR828–AaMYB17 module, thus affecting GST density. Our results suggest that graphene may contribute to yield improvement in A. annua via dynamic physiological processes together with miRNA regulation, and it may thus represent a new cultivation strategy for increasing yield capacity through nanobiotechnology.

OR01-06 Single Nucleus Multi-omics Analysis Identifies Cellular Trajectories And Dynamic Changes In Gene Expression And Chromatin Accessibility In The Pituitary During The Mouse Estrous Cycle

Abstract Disclosure: F.M. Ruf-Zamojski: None. W. Cheng: None. Z. Zhang: None. M. Zamojski: None. G.R. Smith: None. X. Chen: None. N. Mendelev: None. G. Strupinsky: None. C.A. Alonso: None. L. Ongaro Gambino: None. X. Zhou: None. E. Brule: None. M.S. Amper: None. P. Hanna: None. V.D. Nair: None. C.L. Andoniadou: None. J.L. Turgeon: None. O. Troyanskaya: None. E. Zaslavsky: None. D.J. Bernard: None. S.C. Sealfon: None. Single cell multi-omics datasets provide an unparalleled power to resolve gene regulatory circuits underlying cellular function in complex tissues such as the pituitary gland [1, 2]. To better understand cellular plasticity and dynamics in the mouse pituitary during the estrous cycle in vivo, we performed same-cell single nucleus (sn) multi-omics for gene expression and chromatin accessibility on individual pituitaries collected from mice at 9am on each day of the cycle, as well as at 6pm and 11pm on proestrus and at 2am on estrus to capture surge events. Cycle stage was determined by vaginal cytology and post-mortem measurement of serum LH and FSH levels. In total, 102,069 cells passed rigorous quality control (QC, [2]), with over 5,000 cells analyzed per sample, ∼2,000 genes/cell, ∼15,000 ATAC median high-quality fragments, and Transcription Start Site (TSS) enrichment scores above 9 for all samples. We identified 13 well-separated clusters in the snRNAseq and 10 in the snATACseq datasets representing the pituitary cell types that were followed over time. We integrated the gene expression and chromatin accessibility datasets and analyzed changes in cell type proportions, gene expression, and chromatin accessibility through time. We detected major differential gene expression changes in the gonadotropes and lactotropes, which we further investigated using pseudotime trajectory analyses. Several upstream Fshb loci showed dynamic changes during the estrous cycle. Additionally, we uncovered regulatory components of major pituitary genes over time using linkage data analysis.To our knowledge, this is the first study to present detailed and comprehensive data on gene expression and chromatin structure changes at sn resolution in all pituitary cell types during a dynamic physiological process. Thus, it provides critical new resources to the field of endocrinology.

Multifocal acoustic radiation force-based reverberant optical coherence elastography for evaluation of ocular globe biomechanical properties.

Quantifying the biomechanical properties of the whole eye globe can provide a comprehensive understanding of the interactions among interconnected ocular components during dynamic physiological processes. By doing so, clinicians and researchers can gain valuable insights into the mechanisms underlying ocular diseases, such as glaucoma, and design interventions tailored to each patient's unique needs. The aim of this study was to evaluate the feasibility and effectiveness of a multifocal acoustic radiation force (ARF) based reverberant optical coherence elastography (RevOCE) technique for quantifying shear wave speeds in different ocular components simultaneously. We implemented a multifocal ARF technique to generate reverberant shear wave fields, which were then detected using phase-sensitive optical coherence tomography. A 3D-printed acoustic lens array was employed to manipulate a collimated ARF beam generated by an ultrasound transducer, producing multiple focused ARF beams on mouse eye globes ex vivo. RevOCE measurements were conducted using an excitation pulse train consisting of 10 cycles at 3kHz, followed by data processing to produce a volumetric map of the shear wave speed. The results show that the system can successfully generate reverberant shear wave fields in the eye globe, allowing for simultaneous estimation of shear wave speeds in various ocular components, including cornea, iris, lens, sclera, and retina. A comparative analysis revealed notable differences in wave speeds between different parts of the eye, for example, between the apical region of the cornea and the pupillary zone of the iris (). Moreover, the study also revealed regional variations in the biomechanical properties of ocular components as evidenced by greater wave speeds near the apex of the cornea compared to its periphery. The study demonstrated the effectiveness of RevOCE based on a non-invasive multifocal ARF for assessing the biomechanical properties of the whole eyeball. The findings indicate the potential to provide a comprehensive understanding of the mechanical behavior of the whole eye, which could lead to improved diagnosis and treatment of ocular diseases.

Stress and the cardiovascular system performance: current state of the problem (literature overview)

Annotation. Today, the adaptation of people during the warin Ukraine is an important medical and social problem, and for many it serves as an extreme factor affecting changes in the dynamics of physiological processes. Stress is a universal adaptive reaction that causes changes in the functioning of all body systems. One of the adverse consequences of chronic psychological stress is the development of cardiovascular diseases. The purpose of the work is to systematize and analyze the existing problematic aspects of the influence of stress on the activity of the cardiovascular system and to separate the most substantiated approaches to assessing the effects of stress. From the GoogleScholar, PubMed data bases, 45 recent publications on this issue were selected and reviewed. The analysis of literary sources determines the growing interest in the problem of reactivity of the cardiovascular system to psycho-emotional stress. The impact of stress on the human body can be both positive and negative. When stress is short-lived and very strong, it has a beneficial effect, and, on the contrary, if it is intense, acute and long-lasting, it has an adverse effect. One of the tools for objective assessment of stress is heart rate variability, which is recognized as an indicator of autonomic nervous activity. The work examines the invariance of heart rate variability indicators as indicators of the body's stress resistance in the modern distressed anthropogenic environment. Thus, the determination of changes in the regulation of the activity of the cardiovascular system caused by stress at the initial stages has an important prognostic value regarding the development and prevention of possible cardiovascular complications. Observation of stress-related changes in heart rate variability can be used to objectively assess stress. It is worth emphasizing the predictive value of the heart rate variability assessment method, rather than its physiological interpretation.

Engineering of a NIR fluorescent probe for high-fidelity tracking of lipid droplets in living cells and nonalcoholic fatty liver tissues

LDs (Lipid droplets) are key organelles for lipid metabolism and storage, which are closely related to ferroptosis and fatty liver. Due to its small size and highly dynamic nature, developing high-fidelity fluorescent probes for imaging of LDs is crucial for observing the dynamic physiological processes of LDs and investigating LDs-associated diseases. Herein, we synthesized three dicyanoisophorone-based fluorescent probes (DCIMe, DCIJ, and DCIQ) with different electron-donating groups and studied their imaging performance for LDs. The results show that DCIQ is highly polarity sensitive and can perform high-fidelity imaging for LDs, with significantly better performance than DCIMe, DCIJ, and commercial LD probe BODIPY 493/503. Based on this, DCIQ was successfully applied to real-time observe the interplays between LDs and other organelles (mitochondria, lysosomes, and endoplasmic reticulum), and to image the dynamics of LDs with fast scanning mode (0.44 s/frame) and the generation of oleic acid-induced LDs with high-fidelity. Finally, DCIQ was used to study the changes of LDs in the ferroptosis process and nonalcoholic fatty liver disease tissues. Overall, this study provided a powerful tool for high-fidelity imaging of LDs in cells and tissues.

Systematic Proteomics Study on the Embryonic Development of Danio rerio.

The early development of zebrafish (Danio rerio) is a complex and dynamic physiological process involving cell division, differentiation, and movement. Currently, the genome and transcriptome techniques have been widely used to study the embryonic development of zebrafish. However, the research of proteomics based on proteins that directly execute functions is relatively vacant. In this work, we apply label-free quantitative proteomics to explore protein profiling during zebrafish's embryogenesis, and a total of 5961 proteins were identified at 10 stages of zebrafish's early development. The identified proteins were divided into 11 modules according to weighted gene coexpression network analysis (WGCNA), and the characteristics between modules were significantly different. For example, mitochondria-related functions enriched the early development of zebrafish. Primordial germ cell-related proteins were identified at the 4-cell stage, while the eye development event is dominated at 5 days post fertilization (dpf). By combining with published transcriptomics data, we discovered some proteins that may be involved in activating zygotic genes. Meanwhile, 137 novel proteins were identified. This study comprehensively analyzed the dynamic processes in the embryonic development of zebrafish from the perspective of proteomics. It provided solid data support for further understanding of the molecular mechanism of its development.

Time-Course and Tissue-Specific Molecular Responses to Acute Thermal Stress in Japanese Mantis Shrimp Oratosquilla oratoria.

Current understanding of adaptability to high temperatures is increasingly important as extreme weather events that can trigger immediate physiological stress in organisms have occurred more frequently. Here, we tracked transcriptomic responses of gills, hepatopancreas, and muscle to acute thermal exposure at 30 °C for 0.5, 6, and 12 h in an economically important crustacean, Oratosquilla oratoria, to gain a preliminary understanding of the tissue-specific and dynamic physiological regulation process under acute heat stress. The unique physiological responses of muscle, hepatopancreas, and gills to acute thermal stress were associated with protein degradation, lipid transport, and energy metabolism in O. oratoria, respectively. Functional enrichment analysis of differentially expressed transcripts and heat-responsive gene clusters revealed a biphasic protective responsiveness of O. oratoria developed from the early responses of signal transduction, immunity, and cytoskeleton reorganization to the responses dominated by protein turnover and energy metabolism at the mid-late stages under acute heat stress. Noteworthy, trend analysis revealed a consistently upregulated expression pattern of high molecular weight heat shock protein (HSP) family members (HSP60, HSP70, and HSP90) during the entire thermal exposure process, highlighting their importance for maintaining heat resistance in O. oratoria. Documenting the whole process of transcriptional responses at fine temporal resolution will contribute to a far-reaching comprehension of plastic responses to acute heat stress in crustaceans, which is critical in the context of a changing climate.

Aggregation-Induced Emission (AIE), Life and Health.

Light has profoundly impacted modern medicine and healthcare, with numerous luminescent agents and imaging techniques currently being used to assess health and treat diseases. As an emerging concept in luminescence, aggregation-induced emission (AIE) has shown great potential in biological applications due to its advantages in terms of brightness, biocompatibility, photostability, and positive correlation with concentration. This review provides a comprehensive summary of AIE luminogens applied in imaging of biological structure and dynamic physiological processes, disease diagnosis and treatment, and detection and monitoring of specific analytes, followed by representative works. Discussions on critical issues and perspectives on future directions are also included. This review aims to stimulate the interest of researchers from different fields, including chemistry, biology, materials science, medicine, etc., thus promoting the development of AIE in the fields of life and health.

The interaction of endogenous and exogenous factors in the biological rhythms of the Arabesque greenling Pleurogrammus azonus in the Primorie waters

Arabesque greenling Pleurogrammus azonus is an important commercial species in the waters of Russia and Japan. In the Russian waters of the Japan Sea, regular study of its biology was conducted in the waters of the Primorsky Krai, where annual trawl surveys were performed. Material collections covered the entire calendar year. Endogenous rhythms (internal biological clocks) play a crucial role in the coordination of biorhythms of the Arabesque greenling Pleurogrammus azonus. This assumption is confirmed by the different duration of exogenous and endogenous rhythms: the dynamics of the temperature index has a pronounced periodization equal to one astronomical year, and the duration of the mixed rhythms in the dynamics of physiological processes and main components changes with age. The relationship of somatic and generative growth with temperature oscillation is subjected to age-related variability. In juveniles, this relationship is not clearly traceable. At the beginning of puberty period, significant connections are manifested. Then the dependence of growth indicators on the temperature oscillation is reduced, as the selective ability of the Arabesque greenling to choose the temperature range increases. Selective ability to environmental conditions is largely determined not by individual but by group behavior.

Responsive hydrogel dressings for intelligent wound management

AbstractDue to global aging problems, the rising number of patients suffering from chronic or hard‐to‐heal acute wounds imposes a significant burden on healthcare systems. Wound healing is a complicated and dynamic physiological process with distinct molecular and cellular levels at each phase. Despite numerous strategies and advanced wound dressings being developed, successful wound management through smart dressing materials that can adapt to changing wound microenvironments and address the needs of wounds at different stages remains a big challenge. Over the last decade, hydrogel‐based dressings have emerged as one of the most potent biomaterials for wound treatment with favorable biological characteristics and a high potential for active intervention during the wound‐curing process. In the current contribution, we present the most recent progress in smart hydrogel dressings that can regulate the release of therapeutics in response to external stimuli (such as light) as well as endogenous changes in wound environments (e.g., temperature, pH, glucose, and reactive oxygen species) to facilitate wound healing. We also introduce the cutting‐edge technologies of intelligent “sense‐and‐treat” dressings through a combination of built‐in sensors or sensing molecules with responsive hydrogels, which enable real‐time monitoring of wound conditions and prompt on‐demand therapy.

Formulation and Characterization of Polymeric Cross-Linked Hydrogel Patches for Topical Delivery of Antibiotic for Healing Wound Infections.

Wound healing faces significant challenges in clinical settings. It often contains a series of dynamic and complex physiological healing processes. Instead of creams, ointments and solutions, alternative treatment approaches are needed. The main objective of the study was to formulate bacitracin zinc-loaded topical patches as a new therapeutic agent for potential wound healing. A free radical polymerization technique was optimized for synthesis. Polyethylene glycol-8000 (PEG-8000) was chemically cross-linked with acrylic acid in aqueous medium, using Carbopol 934 as a permeation enhancer and tween 80 as surfactant. Ammonium persulfate and N,N'-Methylenebisacrylamide (MBA) were utilized as initiator and cross-linker. FTIR, DSC, TGA, and SEM were performed, and patches were evaluated for swelling dynamics, sol-gel analysis, in vitro drug release in various media. A Franz diffusion cell was used for the permeation study. Irritation and wound healing with the drug-loaded patches were also studied. The characterization studies confirmed the formation of a cross-linked hydrogel network. The highest swelling and drug release were observed in formulations containing highest Polyethylene glycol-8000 and lowest N,N'-Methylenebisacrylamide concentrations. The pH-sensitive behavior of patches was also confirmed as more swelling, drug release and drug permeation across skin were observed at pH 7.4. Fabricated patches showed no sign of irritation or erythema as evaluated by the Draize scale. Faster wound healing was also observed with fabricated patches compared to marketed formulations. Therefore, such a polymeric network can be a promising technology for speeding up wound healing and minor skin injuries through enhanced drug deposition.

Person-centered approach to work with drug addicts on substitution maintenance therapy

IntroductionAccording to the United Nations World Drug Report 2019, there are an estimated 53 million opioid users[1]. Health problems, social problems associated with this abuse are the result of a complex interaction between psychoactive substances, the patient and the environment. There are two main approaches in the treatment - aimed at complete abstinence from the use of a psychoactive substance and substitution maintenance therapy using methadone and buprenorphine [2]. This is due to the pharmacological effects of narcotic substances, the dynamics of physiological processes and the general state of health with the systematic use of psychoactive substances.ObjectivesThe problem of the use of narcotic substances must be considered not only as a physiological problem, but also as a problem of a person resorting to drugs in a specific social situation. In this case, curative and rehabilitation work acquires new content and new opportunities. The emergence of addiction depends on two main reasons: on the one hand, these are certain specific personality traits of a person, formed primarily by the family, and on the other hand, external factors such as the influence of friends, curiosity, life difficulties experienced and other personal problems. The greatest danger of the formation of drug addiction occurs in the case of simultaneous exposure to both groups of causes.MethodsThe study interviewed 123 patients aged 23 to 45 years (109 men and 14 women) diagnosed with opioid addiction. Of these, 17 patients with a period of abuse of up to three years and 105 - longer than three years, respectively. Personality disorders were assessed using the 16-factor Cattell Personality Questionnaire for the study of personality traits [3], the multi-aspect MMPI methodology (mini-mult) [4], and the Luscher color choice method [5].Results14 drug addicts (82%) with a period of abuse of less than 3 years were characterized by impulsivity, reduced stress resistance, risk appetite; in 83 drug addicts (79%) with a period of abuse longer than 3 years, persistent psychosocial maladjustment, communication difficulties, conflicts were detected, social norms were disregarded, increased readiness for open manifestation of aggression; 14 women (100%) had features of mental rigidity, disregard for social norms, conflict, impulsiveness; 88 men (81%) had emotional instability, excitability, hostility.ConclusionsThe formation of opioid dependence is influenced by both the psychophysiological characteristics and the pathopsychological changes that occurred during the use of a psychoactive substance.Addiction therapy should include a psychological analysis of risk factors.Selection of psychological options for social adaptation that contribute to the maximum possible realization of the individual’s potential, will increase the effectiveness of substitution therapy and accelerate the resocialization of drug addicts.Disclosure of InterestNone Declared

Design Considerations, Formulation Approaches, and Strategic Advances of Hydrogel Dressings for Chronic Wound Management.

Wound healing is a complex and dynamic physiological process consisting of a series of cellular and molecular events that initiate immediately after a tissue lesion, to reconstruct the skin layer. It is indubitable that patients with chronic wounds, severely infected wounds, or any metabolic disorder of the wound microenvironment always endure severe pain and discomfort that affect their quality of life. It is essential to treat chronic wounds for conserving the physical as well as mental well-being of affected patients and for convalescing to improve their quality of life. For supporting and augmenting the healing process, the selection of pertinent wound dressing is essential. A substantial reduction in healing duration, disability, associated cost, and risk of recurrent infections can be achieved via engineering wound dressings. Hydrogels play a leading role in the path of engineering ideal wound dressings. Hydrogels, comprising water to a large extent, providing a moist environment, being comfortable to patients, and having biocompatible and biodegradable properties, have found their success as suitable wound dressings in the market. The exploitation of hydrogels is increasing perpetually after substantiation of their broader therapeutic actions owing to their resemblance to dermal tissues, their capability to stimulate partial skin regeneration, and their ability to incorporate therapeutic moieties promoting wound healing. This review entails properties of hydrogel supporting wound healing, types of hydrogels, cross-linking mechanisms, design considerations, and formulation strategies of hydrogel engineering. Various categories of hydrogel wound dressing fabricated recently are discussed based on their gel network composition, degradability, and physical and chemical cross-linking mechanisms, which provide an outlook regarding the importance of tailoring the physicochemical properties of hydrogels. The examples of marketed hydrogel wound dressings are also incorporated along with the future perspectives and challenges associated with them.