Biochemical Barriers Research Articles

A Wurster-Type Covalent Organic Framework with Internal Electron Transfer-Enhanced Catalytic Capacity for Tumor Therapy.

The low immunogenicity of tumors, along with the abnormal structural and biochemical barriers of tumor-associated vasculature, impedes the infiltration and function of effector T cells at the tumor site, severely inhibiting the efficacy of antitumor immunotherapy. In this study, a cobaloxime catalyst and STING agonist (MSA-2)-coloaded Wurster-type covalent organic framework (Co-TB COF-M) with internal electron transfer-enhanced catalytic capacity was developed as a COF-based immune activator. The covalently anchored cobaloxime adjusts the energy band structure of TB COF and provides it with good substrate adsorption sites, enabling it to act as an electron transmission bridge between the COF and substrate in proton reduction catalytic reactions. This property significantly enhances the sonodynamic catalytic performance. Under sono-irradiation, Co-TB COF-M can produce a substantial amount of reactive oxygen species (ROS) to induce Gasdermin D-mediated pro-inflammatory pyroptosis, thereby effectively enhancing the immunogenicity of tumors. Furthermore, MSA-2 is specifically released in response to ROS at the tumor site, minimizing the off-target side effects. More importantly, Co-TB COF-induced STING activation normalizes tumor vasculature and increases the expression of endothelial T cell adhesion molecules, which greatly enhance the infiltration and function of effector T cells. Thus, Co-TB COF-M as an immune activator could remold the tumor microenvironment, leading to increased infiltration and an improved function of T cells for immunotherapy.

Advanced Oral Drug Delivery Systems for Combating and Preventing Paediatric Periodontal Disease

: The oral route is the most common route of administration of drugs. Over 90% of all the available marketed pharmaceutical products are oral formulations. Oral drugs are used in different courses of treatment including the prevention of tooth decay. Tooth decay is the permanent damage of the enamel which leads to the formation of cavities. It can be prevented with good oral hygiene and enough fluorides in the body. Fluorides can be administered both topically (toothpastes) and systemically (supplements). Fluoride supplements fall under oral drug delivery systems. They come in the form of tablets, lozenges, and liquids. However, challenges are faced when it comes to oral drug delivery in children. The development of paediatric drugs is a difficult undertaking since many pharmaceutically active compounds have low water solubility, instability, or an unpleasant taste. Children are unable to tolerate bitter or unpleasant- tasting formulations, as well as huge pills and capsules. Due to various biological, biochemical, and physical barriers faced by oral drug delivery systems, new approaches have been developed to address these challenges such as the application of nanotechnology in drug development. Jellies for oral administration on the other hand are a new approach for the delivery of drugs with bitter tastes as well as for age groups such as children and elders. They are clear, translucent, or non-greasy semisolid products that can be used both externally and internally. In-depth, aspects of these factors will be discussed in this review paper including oral dosage forms for paediatrics, tooth decay and its pathogenesis, preventive measures and setbacks of each measure as well as the future perspectives.

Percutaneous Penetration and Dermal Exposure Risk Assessment of UV Absorbents in Sunscreens and Isolation Cosmetics.

Ultraviolet absorbents (UVs) make up a group of industrial chemicals that is used in various consumer products and industrial applications. Due to their extensive production and usage, UVs have been detected in multiple environmental matrixes. Recently, UVs have garnered significant attention because of their probable adverse impacts on human health and the environment. This study examines UVs levels in sunscreens and isolation cosmetics and further assesses human exposure to UVs through the application of cosmetics. The total concentrations of nine UVs in 87 sunscreen and isolation cosmetic products ranged from 75.5 to 4.25 × 104 ng/g. Among them, 2-(2-hydroxy-5-methyl-phenyl)benzotriazole (UV-P) and 2-hydroxy-4-(octoxy)benzophenone (UV-531) had the highest concentrations. Use of the EpiSkin model indicated rapid absorption and strong dermal penetration by UV-328 following 36 h of exposure with a cumulative absorption rate of 41.8% ± 2.82%. Other congeners are expected to be distributed in the dermal tissue and donor fluid. Furthermore, this study explored potential mechanisms implicating skin biochemical barriers in the metabolism and transport of UVs. The potential of UVs to act as substrates and inhibitors of P450 enzymes was assessed, and their metabolites were predicted. Molecular docking simulations demonstrated that UVs can significantly interact and bind with three transport proteins in skin: MDR1, OATP2B1, and OATP3A1. Daily UVs exposure through the skin was assessed, revealing that dermal absorption levels of UV-P in sunscreen sprays (4.66 × 103 ng/(kg bw day)) and sunscreens (6.01 × 103 ng/(kg bw day)) were close to or exceeded the reference dose (RfD) and therefore require more attention.

ROLE OF INORGANIC PARTICLES FOR THE FORMULATION OF NANOPARTICLES: A REVIEW

Inorganic particles do not have carbon in their backbone and are produced through various geochemical processes, i.e. they are not biological in nature. It is a common practice to use inorganic particles to formulate nanoparticles as their size is near nanoscale dimensions. Various inorganic particles such as silver, gold, silica, alumina and magnetite have been used to fabricate nanoparticles. These nanoparticles are used in different fields, such as magnetic recording, chemical sensing, anti-microbial assays and enzyme immobilization. They have several advantages due to their increased surface area-to-volume ratio, enhancing their reactivity. This review will discuss various inorganic particles used for nanoparticle preparation and their structure, properties, and applications in biomedical engineering. The major applications of formulated nanoparticles are used in biomedicines for drug delivery. They can deliver the drug to the specific site by crossing many biophysical, biochemical and biological barriers.

Nanomedicine: A New Frontier in Alzheimer's Disease Drug Targeting.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder affecting elderly individuals, characterized by progressive cognitive decline leading to dementia. This review examines the challenges posed by anatomical and biochemical barriers such as the blood-brain barrier (BBB), blood-cerebrospinal fluid barrier (BCSFB), and p-glycoproteins in delivering effective therapeutic agents to the central nervous system (CNS) for AD treatment. This article outlines the fundamental role of acetylcholinesterase inhibitors (AChEIs) and NMDA(N-Methyl-D-Aspartate) receptor antagonists in conventional AD therapy and highlights their limitations in terms of brain-specific delivery. It delves into the intricacies of BBB and pglycoprotein-mediated efflux mechanisms that impede drug transport to the CNS. The review further discusses cutting-edge nanomedicine-based strategies, detailing their composition and mechanisms that enable effective bypassing of BBB and enhancing drug accumulation in brain tissues. Conventional therapies, namely AChEIs and NMDA receptor antagonists, have shown limited efficacy and are hindered by suboptimal brain penetration. The advent of nanotechnology-driven therapeutic delivery systems offers promising strategies to enhance CNS targeting and bioavailability, thereby addressing the shortcomings of conventional treatments. Various nanomedicines, encompassing polymeric and metallic nanoparticles (MNPs), solid lipid nanoparticles (SLNs), liposomes, micelles, dendrimers, nanoemulsions, and carbon nanotubes, have been investigated for their potential in delivering anti-AD agents like AChEIs, polyphenols, curcumin, and resveratrol. These nanocarriers exhibit the ability to traverse the BBB and deliver therapeutic payloads to the brain, thereby holding immense potential for effective AD treatment and early diagnostic approaches. Notably, nanocarriers loaded with AChEIs have shown promising results in preclinical studies, exhibiting improved therapeutic efficacy and sustained release profiles. This review underscores the urgency of innovative drug delivery approaches to overcome barriers in AD therapy. Nanomedicine-based solutions offer a promising avenue for achieving effective CNS targeting, enabling enhanced bioavailability and sustained therapeutic effects. As ongoing research continues to elucidate the complexities of CNS drug delivery, these advancements hold great potential for revolutionizing AD treatment and diagnosis.

The role of supervision and motivation during exercise on physical and mental health in older adults: a study protocol for a randomized controlled trial (PRO-Training project)

BackgroundAlthough supervised exercise is frequently recommended for older adults, its superiority over unsupervised exercise remains uncertain. Furthermore, whether motivational techniques could help to enhance the effectiveness of the latter remains to be elucidated. The present randomized controlled trial aims to determine the role of supervision and motivational strategies on the safety, adherence, efficacy, and cost-effectiveness of different exercise programs for improving physical and mental health in older adults.MethodsParticipants (n = 120, aged 60–75 years) will be randomly allocated into five groups: 1-Control (CON), 2-Supervised exercise without motivational intervention (SUP), 3- Supervised exercise with motivational intervention (SUP +), 4- Unsupervised exercise without motivational intervention (UNSUP) and 5- Unsupervised exercise with motivational intervention (UNSUP +). Over 24 weeks, all exercise groups will participate in a multicomponent exercise program three times/week (performed in group classes at a center for SUP and SUP + , or home without supervision but with the help of a mobile app for UNSUP and UNSUP +), while the CON group will maintain their usual lifestyle. The motivational intervention (for SUP + and UNSUP + groups) will be based on the self-determination theory, including strategies such as phone calls, interactive workshops, motivational messages, informative infographics and videos. Primary outcomes will include safety, adherence, costs, and lower-body muscular function using a leg press machine. Secondary outcomes will include upper-body muscular function, physical and cardiorespiratory function, blood pressure and heart rate, body composition, health-related quality of life, cognitive performance, anxiety, depression, physical activity levels, sleep and sedentarism, biochemical markers, motivators and barriers to exercise. Assessments will be conducted at baseline, mid-intervention (i.e., week 13), at the end of the intervention (i.e., week 25), and 24 weeks later (i.e., week 49).DiscussionThe findings of this trial might provide valuable insights into the role of supervision and motivational strategies on the effectiveness of exercise programs for older adults. Additionally, the study could contribute to developing cost-effective interventions, supporting the design of future public policies for healthy aging.Trial registrationNCT05619250. Registered 16 November 2022.

Understanding gut microbiome-based machine learning platforms: A review on therapeutic approaches using deep learning.

Human beings possess trillions of microbial cells in a symbiotic relationship. This relationship benefits both partners for a long time. The gut microbiota helps in many bodily functions from harvesting energy from digested food to strengthening biochemical barriers of the gut and intestine. But the changes in microbiota composition and bacteria that can enter the gastrointestinal tract can cause infection. Several approaches like culture-independent techniques such as high-throughput and meta-omics projects targeting 16S ribosomal RNA (rRNA) sequencing are popular methods to investigate the composition of the human gastrointestinal tract microbiota and taxonomically characterizing microbial communities. The microbiota conformation and diversity should be provided by whole-genome shotgun metagenomic sequencing of site-specific community DNA associating genome mapping, gene inventory, and metabolic remodelling and reformation, to ease the functional study of human microbiota. Preliminary examination of the therapeutic potency for dysbiosis-associated diseases permits investigation of pharmacokinetic-pharmacodynamic changes in microbial communities for escalation of treatment and dosage plan. Gut microbiome study is an integration of metagenomics which has influenced the field in the last two decades. And the incorporation of artificial intelligence and deep learning through "omics-based" methods and microfluidic evaluation enhanced the capability of identification of thousands of microbes.

Disruption of Super-Enhancers in Activated Pancreatic Stellate Cells Facilitates Chemotherapy and Immunotherapy in Pancreatic Cancer.

One major obstacle in the drug treatment of pancreatic ductal adenocarcinoma (PDAC) is its highly fibrotic tumor microenvironment, which is replete with activated pancreatic stellate cells (a-PSCs). These a-PSCs generate abundant extracellular matrix and secrete various cytokines to form biophysical and biochemical barriers, impeding drug access to tumor tissues. Therefore, it is imperative to develop a strategy for reversing PSC activation and thereby removing the barriers to facilitate PDAC drug treatment. Herein, by integrating chromatin immunoprecipitation (ChIP)-seq, Assays for Transposase-Accessible Chromatin (ATAC)-seq, and RNA-seq techniques, this work reveals that super-enhancers (SEs) promote the expression of various genes involved in PSC activation. Disruption of SE-associated transcription with JQ1 reverses the activated phenotype of a-PSCs and decreases stromal fibrosis in both orthotopic and patient-derived xenograft (PDX) models. More importantly, disruption of SEs by JQ1 treatments promotes vascularization, facilitates drug delivery, and alters the immune landscape in PDAC, thereby improving the efficacies of both chemotherapy (with gemcitabine) and immunotherapy (with IL-12). In summary, this study not only elucidates the contribution of SEs of a-PSCs in shaping the PDAC tumor microenvironment but also highlights that targeting SEs in a-PSCs may become a gate-opening strategy that benefits PDAC drug therapy by removing stromal barriers.

Cell size differences affect photosynthetic capacity in a Mesoamerican and an Andean genotype of Phaseolus vulgaris L.

The efficiency of CO2 flux in the leaf is hindered by a several structural and biochemical barriers which affect the overall net photosynthesis. However, the dearth of information about the genetic control of these features is limiting our ability for genetic manipulation. We performed a comparative analysis between three-week-old plants of a Mesoamerican and an Andean cultivar of Phaseolus vulgaris at variable light and CO2 levels. The Mesoamerican bean had higher photosynthetic rate, maximum rate of rubisco carboxylase activity and maximum rate of photosynthetic electron transport at light saturation conditions than its Andean counterpart. Leaf anatomy comparison between genotypes showed that the Mesoamerican bean had smaller cell sizes than the Andean bean. Smaller epidermal cells in the Mesoamerican bean resulted in higher stomata density and consequently higher stomatal conductance for water vapor and CO2 than in the Andean bean. Likewise, smaller palisade and spongy mesophyll cells in the Mesoamerican than in the Andean bean increased the cell surface area per unit of volume and consequently increased mesophyll conductance. Finally, smaller cells in the Mesoamerican also increased chlorophyll and protein content per unit of leaf area. In summary, we show that different cell sizes controls the overall net photosynthesis and could be used as a target for genetic manipulation to improve photosynthesis.

Hypoxic 3D Tumor Model for Evaluating of CAR-T Cell Therapy In Vitro.

Solid tumors contain abnormal physical and biochemical barriers that hinder chimeric antigen receptor (CAR) T cell therapies. However, there is a lack of understanding on how the solid tumor microenvironment (e.g. hypoxia)modulates CAR-T cell function. Hypoxia is a common feature of many advanced solid tumors that contributes to reprogramming of cancer and T cell metabolism as well as their phenotypes and interactions.To gain insights into the activities of CAR-T cells in solid tumors and to assess the effectiveness of new combination treatments involving CAR-T cells, in vitro models that faithfully reflect CAR-T cell-solid tumor interactions under physiologically relevant tumor microenvironment is needed. Here we demonstrate how to establish a hypoxic 3-dimensional (3-D) tumor model using a cleanroom-free, micromilling-based microdevice and assess the efficacy of the combination treatment with CAR-T cells and PD-1/PD-L1 inhibition.

A single photodynamic priming protocol augments delivery of ⍺-PD-L1 mAbs and induces immunogenic cell death in head and neck tumors.

Photodynamic priming (PDP) leverages the photobiological effects of subtherapeutic photodynamic therapy (PDT) regimens to modulate the tumor vasculature and stroma. PDP also sensitizes tumors to secondary therapies, such as immunotherapy by inducing a cascade of molecular events, including immunogenic cell death (ICD). We and others have shown that PDP improves the delivery of antibodies, among other theranostic agents. However, it is not known whether a single PDP protocol is capable of both inducing ICD in vivo and augmenting the delivery of immune checkpoint inhibitors. In this rapid communication, we show for the first time that a single PDP protocol using liposomal benzoporphyrin derivative (Lipo-BPD, 0.25 mg/kg) with 690 nm light (75 J/cm2 , 100 mW/cm2 ) simultaneously doubles the delivery of ⍺-PD-L1 antibodies in murine AT-84 head and neck tumors and induces ICD in vivo. ICD was observed as a 3-11 fold increase in tumor cell exposure of damage-associated molecular patterns (Calreticulin, HMGB1, and HSP70). These findings suggest that this single, highly translatable PDP protocol using clinically relevant Lipo-BPD holds potential for improving immunotherapy outcomes in head and neck cancer. It can do so by simultaneously overcoming physical barriers to the delivery of immune checkpoint inhibitors, and biochemical barriers that contribute to immunosuppression.

Utilization of primary and secondary biochemical compounds in cotton as diagnostic markers for measuring resistance to cotton leaf curl virus.

Cotton (Gossypium hirsutum L.) is one of the most important staple fibrous crops cultivated in India and globally. However, its production and quality are greatly hampered by cotton leaf curl disease (CLCuD) caused by cotton leaf curl virus (CLCuV). Therefore, the aim of the present study was to investigate the biochemical mechanisms associated with CLCuD resistance in contrasting cotton genotypes. Four commercial cotton varieties with susceptible (HS 6 and RCH-134 BG-II) and resistant (HS 1236 and Bunty) responses were used to analyze the role of primary (sugar, protein, and chlorophyll) and secondary (gossypol, phenol, and tannin) biochemical compounds produced by the plants against infection by CLCuV. The resistant cultivars with increased activity of protein, phenol, and tannin exhibited biochemical barriers against CLCuV infection, imparting resistance in cotton cultivars. Reducing sugar in the healthy plants of the susceptible Bt cultivar RCH 134 BG-II exhibited the highest value of 1.67 mg/g at 90 days. In contrast, the lowest value of 0.07 mg g-1 was observed at 60 DAS in the highly diseased plants of the susceptible hybrid HS 6. Higher phenol content (0.70 mg g-1) was observed at 90 DAS in resistant cultivars, whereas highly susceptible plants exhibited the least phenol (0.25 mg g-1) at 90 DAS. The lowest protein activity was observed at 120 DAS in susceptible cultivars HS 6 (9.4 mg g-1) followed by RCH 134 BG-II (10.5 mg g-1). However, other biochemical compounds, including chlorophyll, sugar, and gossypol, did not show a significant role in resistance against CLCuV. The disease progression analysis in susceptible cultivars revealed non-significant differences between the two susceptible varieties. Nevertheless, these compounds are virtually associated with the basic physiological and metabolic mechanisms of cotton plants. Among the primary biochemical compounds, only protein activity was proposed as the first line of defense in cotton against CLCuV. The secondary level of defense line in resistance showed the activity of secondary biochemical compounds phenol and tannins, which displayed a significant increase in their levels while imparting resistance against CLCuV in cotton.

Sonodynamic therapy of glioblastoma mediated by platelets with ultrasound-triggered drug release

Sonodynamic therapy (SDT) has aroused great interest for its potential in the treatment of glioblastoma (GBM). SDT relies on tumor-selective accumulation of a sonosensitizer that is activated by ultrasound irradiation (UI) to generate cytotoxic actions. The efficacy of GBM-SDT depends on sufficient sonosensitizer buildup in the tumor, which is, however, seriously hampered by the anatomical and biochemical barriers of the GBM. To overcome this difficulty, we herein propose a delivery strategy of ‘platelets with ultrasound-triggered release property’, which takes advantage of 1) the platelets’ ability to carry cargo and release cargo upon activation, and 2) the ROS-generating property of SDT. To provide proof of concept for the strategy, we first stably loaded platelets with IOPD-Ce6, a nano-formed sonosensitizer consisting of iron oxide nanoparticles coated with polyglycerol and doxorubicin and loaded with chlorine e6. UI of the IOPD-Ce6-loaded platelets (IOPD-Ce6@Plt) elicited ROS generation in the IOPD-Ce6@Plt, which were immediately activated to release IOPD-Ce6 into GBM cells in co-culture which, when subjected to a second time of UI, exhibited pronounced ROS production, DNA injury, viability loss, and cell death in the GBM cells. In the in vivo experiments, mice bearing intracranial GBM grafts exhibited substantial tumor distribution of IOPD-Ce6 following intravenous injection of IOPD-Ce6@Plt and subsequent UI at the tumor site. The GBM grafts then exhibited pronounced cell injury and death after another round of UI of the tumors. Finally, the growth of intra-cranial GBM grafts was significantly slowed when an SDT protocol consisting of an intravenous IOPD-Ce6@Plt injection followed by multiple times of tumor UI had been applied twice to the mice. Our results are strong evidence for the idea that platelets are sound and amenable carriers to deliver sonosensitizers in the GBM in an ultrasound-triggered manner and thus to produce highly targeted and effective SDT of GBM.

Stressing environmental conditions in the “petrified forest” from the Mata Sequence in the Triassic context of the Paraná Basin

This study deals with the Piscina Outcrop, a Rhaetic reddish conglomeratic sandstone containing silicified logs which corresponds to the Mata Sequence in the southernmost Brazilian Paraná Basin. We performed ground-penetrating radar (GPR) analysis and the results ratified previous sequence stratigraphy analysis indicating that these deposits correspond to architectural elements exclusively related with the filling processes of fluvial channels. The erosive unconformity identified at the boundary between the Mata Sequence and the underlying rock packages could represent a considerable depositional hiatus. The integration of the GPR results with sedimentological and paleovertebrate data from a nearby outcrop at slightly lower topographic level indicated that the layer with the fossil woods is superimposed through an erosive unconformity to the stratigraphic levels corresponding to the Hyperodapedon Assemblage Zone of Carnian age from the basal portion of the Candelária Sequence. The wood assemblage was composed exclusively of araucarian coniferous stems identified as Agathoxylon (cf. Agathoxylon). The wood growth patterns were mainly characterized by woods showing indistinct growth rings, with latewood mostly restricted to one cell in each ring, suggesting weak seasonality and short-term, periodic droughts. Rare specimens with absent growth rings were also present. Oscillations in growth ring width and the common occurrence of false rings were likely linked to plant exposure to climatic instability. Anatomical evidence pointed to active biochemical responses to intense and extensive biological attack of fungi and arthropods. The dominant presence of carbon in the elemental composition of a dark substance filling many tracheid lumens suggested a very likely affinity with polyphenol remnants in biochemical barriers. The set of wood signatures seems to be linked to regional stressing conditions rather than to the paleolatitudinal location when compared to other key South American basins during the Rhaetic. An allochthonous taphocoenosis is the most likely taphonomic interpretation for this wood assemblage. The logs were probably incorporated into the stream through the collapse of riparian areas and buried in the fluvial channel by high-energy flows after biotic and abiotic decay processes during lifetime and secondarily through exposition before entombment in a river channel.

Attempts to limit sporulation in the probiotic strain Bacillus subtilis BG01-4TM through mutation accumulation and selection.

The use of bacterial spores in probiotics over viable loads of bacteria has many advantages, including the durability of spores, which allows spore-based probiotics to effectively traverse the various biochemical barriers present in the gastrointestinal tract. However, the majority of spore-based probiotics developed currently aim to treat adults, and there is a litany of differences between the adult and infant intestinal systems, including the immaturity and low microbial species diversity observed within the intestines of infants. These differences are only further exacerbated in premature infants with necrotizing enterocolitis (NEC) and indicates that what may be appropriate for an adult or even a healthy full-term infant may not be suited for an unhealthy premature infant. Complications from using spore-based probiotics for premature infants with NEC may involve the spores remaining dormant and adhering to the intestinal epithelia, the out-competing of commensal bacteria by spores, and most importantly the innate antibiotic resistance of spores. Also, the ability of Bacillus subtilis to produce spores under duress may result in less B. subtilis perishing within the intestines and releasing membrane branched-chain fatty acids. The isolate B. subtilis BG01-4TM is a proprietary strain developed by Vernx Biotechnology through accumulating mutations within the BG01-4TM genome in a serial batch culture. Strain BG01-4TM was provided as a non-spore-forming B. subtilis , but a positive sporulation status for BG01-4TM was confirmed through in vitro testing and suggested that selection for the sporulation defective genes could occur within an environment that would select against sporulation. The durability of key sporulation genes was ratified in this study, as the ability of BG01-4TM to produce spores was not eliminated by the attempts to select against sporulation genes in BG01-4TM by the epigenetic factors of high glucose and low pH. However, a variation in the genes in isolate BG01-4-8 involved in the regulation of sporulation is believed to have occurred during the mutation selection from the parent strain BG01-4TM. An alteration in selected sporulation regulation genes is expected to have occurred from BG01-4TM to BG01-4-8, with BG01-4-8 producing spores within 24 h, ~48 h quicker than BG01-4TM.

STING-activating nanoparticles normalize the vascular-immune interface to potentiate cancer immunotherapy.

The tumor-associated vasculature imposes major structural and biochemical barriers to the infiltration of effector T cells and effective tumor control. Correlations between stimulator of interferon genes (STING) pathway activation and spontaneous T cell infiltration in human cancers led us to evaluate the effect of STING-activating nanoparticles (STANs), which are a polymersome-based platform for the delivery of a cyclic dinucleotide STING agonist, on the tumor vasculature and attendant effects on T cell infiltration and antitumor function. In multiple mouse tumor models, intravenous administration of STANs promoted vascular normalization, evidenced by improved vascular integrity, reduced tumor hypoxia, and increased endothelial cell expression of T cell adhesion molecules. STAN-mediated vascular reprogramming enhanced the infiltration, proliferation, and function of antitumor T cells and potentiated the response to immune checkpoint inhibitors and adoptive T cell therapy. We present STANs as a multimodal platform that activates and normalizes the tumor microenvironment to enhance T cell infiltration and function and augments responses to immunotherapy.

The Role of Natural Physical, Mechanical, and Biochemical Barriers as Innate Immunity: A Narrative Literature Review

The specialized epithelial outer layer, including the skin and mucosal surfaces, is relatively resistant to most environmental hazards and resistant to infection by disease-causing microorganisms. This literature review aimed to describe the role of natural physical, mechanical, and biochemical barriers in innate immunity. The physical barrier that protects against damage and infection consists of closely related epithelial cells, including the skin and the sheet membranes that line the digestive tract, genitourinary, and breathing. The epithelial surface also provides a biochemical barrier by synthesizing and secreting substances intended to trap or destroy microorganisms (chemicals derived from the epithelium). Mucus, sweat, saliva, tears, and earwax are examples of biochemical secretions that can trap and kill potential disease-causing microorganisms. Microorganisms in the microbiome do not usually cause disease, although some are opportunistic in that they can cause disease if the integrity of the body surface is compromised or the individual's immune or inflammatory systems are damaged. In conclusion, natural barriers include physical, mechanical, and biochemical on the surface of the body and are present from birth to prevent damage by substances in the environment and prevent infection by pathogenic microorganisms.

Recent innovations in oral drug delivery systems: Examining current challenges and future opportunities for enhanced therapeutic efficacy

Introduction: Oral drug delivery remains a cornerstone of therapeutic administration due to its ease of use and broad patient acceptance. However, delivering drugs orally poses significant challenges due to the complex and hostile environment of the gastrointestinal tract (GIT), including anatomical, biochemical, and physiological barriers. Aim: This article aims to explore recent innovations in oral drug delivery systems, focusing on addressing current challenges and identifying future opportunities for enhancing therapeutic efficacy. Methods: The study reviews advancements in oral drug delivery systems, including novel nanomedicines, microfabricated devices, and targeted delivery technologies. It synthesizes research findings from recent literature to highlight the evolution of these technologies and their impact on drug delivery. Results: Recent innovations include nanoparticles, microemulsions, and microfabricated devices, which enhance drug stability, targeting, and bioavailability. Nanoparticles, such as liposomes and solid lipid nanoparticles, protect drugs from the GIT environment and improve their absorption. Microfabricated devices, such as microneedles and micropatches, offer controlled and targeted drug release. Additionally, advancements in smart drug delivery systems, such as pH-sensitive and enzyme-responsive systems, provide precise control over drug release. Conclusion: Advances in oral drug delivery systems have significantly improved the ability to overcome GIT barriers, enhancing the effectiveness of oral medications.

Миграция 137Cs в экосистеме поймы р. Унеча

Purpose: to study the ¹³⁷Cs migration and concentration in the alluvial soils profile and the radionuclide transfer to plants in the river Unecha floodplain ecosystem. Materials and methods. Field studies were carried out in 2019–2021 in Bryansk region (Klintsovsky district, the village of Lopatni, the right bank of the river Unecha, the current reclamation system). The density of ¹³⁷Cs contamination of the territory after the Chernobyl accident was 185–555 kBq/m². Conjugated soil and plant samples were taken in various sub-systems of the floodplain (near-channel, central, near-terrace). Agrochemical indicators of fer-tility and ¹³⁷Cs specific activity in soil and plants were determined using generally accepted laboratory methods. Results. A strong variability of the agrochemical parameters of alluvial soils in layers every 5 cm within 0–20 cm was determined. A high content of mobile phos-phorus and a low content of potassium, a strongly acid reaction of the environment, and a ten-dency to the growth in the organic carbon content from the near-channel to near-terraсе floodplain subsystem was found. The ¹³⁷Cs horizontal distribution in the river Unecha flood-plain soils was determined by soil genesis of the floodplain subsystems; the maximum specific activity of ¹³⁷Cs 3953 Bq/kg was found in the near-terrace part of the floodplain. The ¹³⁷Cs maximum concentration was found in the near-channel and central subsystem in the soil layer of 0–5 cm, and in the near-terrace subsystem in the layer of 5–10 cm. In the floodplain of the river Unecha, the ¹³⁷Cs coefficient transfer from soil to plants decreases from the central to the near-channel and near-terrace. Conclusions. The formation of agrochemical indicators of al-luvial soil fertility and the ¹³⁷Cs vertical distribution is determined by soil genesis in floodplain subsystems; it can be uniformly decreasing or concentrated in separate layers at biochemical barriers. In the floodplain ecosystem, the ¹³⁷Cs concentration in the 0–20 cm layer increases from the near-channel to near-terrace subsystem. Forage production under the conditions of radioactive contamination of the near-river and central parts of the floodplain is possible without the use of protective measures.

Engineering the Tumor Immune Microenvironment through Minimally Invasive Interventions.

The tumor microenvironment (TME) is a unique landscape that poses several physical, biochemical, and immune barriers to anti-cancer therapies. The rapidly evolving field of immuno-engineering provides new opportunities to dismantle the tumor immune microenvironment by efficient tumor destruction. Systemic delivery of such treatments can often have limited local effects, leading to unwanted offsite effects such as systemic toxicity and tumor resistance. Interventional radiologists use contemporary image-guided techniques to locally deliver these therapies to modulate the immunosuppressive TME, further accelerating tumor death and invoking a better anti-tumor response. These involve local therapies such as intratumoral drug delivery, nanorobots, nanoparticles, and implantable microdevices. Physical therapies such as photodynamic therapy, electroporation, hyperthermia, hypothermia, ultrasound therapy, histotripsy, and radiotherapy are also available for local tumor destruction. While the interventional radiologist can only locally manipulate the TME, there are systemic offsite recruitments of the immune response. This is known as the abscopal effect, which leads to more significant anti-tumoral downstream effects. Local delivery of modern immunoengineering methods such as locoregional CAR-T therapy combined with immune checkpoint inhibitors efficaciously modulates the immunosuppressive TME. This review highlights the various advances and technologies available now to change the TME and revolutionize oncology from a minimally invasive viewpoint.