Biological Impact Research Articles

Comprehensive Blood Metabolome and Exposome Analysis, Annotation, and Interpretation in E-Waste Workers

Background: Electronic and electrical waste (e-waste) production has emerged to be of global environmental public health concern. E-waste workers, who are frequently exposed to hazardous chemicals through occupational activities, face considerable health risks. Methods: To investigate the metabolic and exposomic changes in these workers, we analyzed whole blood samples from 100 male e-waste workers and 49 controls from the GEOHealth II project (2017–2018 in Accra, Ghana) using LC-MS/MS. A specialized computational workflow was established for exposomics data analysis, incorporating two curated reference libraries for metabolome and exposome profiling. Two feature detection algorithms, asari and centWave, were applied. Results: In comparison to centWave, asari showed better sensitivity in detecting MS features, particularly at trace levels. Principal component analysis demonstrated distinct metabolic profiles between e-waste workers and controls, revealing significant disruptions in key metabolic pathways, including steroid hormone biosynthesis, drug metabolism, bile acid biosynthesis, vitamin metabolism, and prostaglandin biosynthesis. Correlation analyses linked metal exposures to alterations in hundreds to thousands of metabolic features. Functional enrichment analysis highlighted significant perturbations in pathways related to liver function, vitamin metabolism, linoleate metabolism, and dynorphin signaling, with the latter being observed for the first time in e-waste workers. Conclusions: This study provides new insights into the biological impact of prolonged metal exposure in e-waste workers.

Biological and clinical role of TREM2 in liver diseases

Liver diseases constitute a major health burden worldwide, accounting for more than 4% of all disease-related mortalities. While the incidence of viral hepatitis is expected to decrease, metabolic liver disorders are increasingly diagnosed. Liver pathology is diverse, with functional and molecular alterations in both parenchymal and mesenchymal cells, including immune cells. Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor of the immunoglobulin superfamily and mainly expressed on myeloid cells. Several studies have demonstrated that TREM2 plays a critical role in tissue physiology and various pathological conditions. TREM2 is recognized as being associated with the development of liver diseases by regulating tissue homeostasis and the immune microenvironment. The biological and clinical impact of TREM2 is complex, given its diverse context-dependent functions. This review aims to summarize recent progress in understanding the association between TREM2 and different liver disorders and shed light on the clinical significance of targeting TREM2.

Interleukin-38 ameliorates myocardial Ischemia-Reperfusion injury via inhibition of NLRP3 inflammasome activation in fibroblasts through the IL-1R8/SYK axis

ObjectiveAlthough IL-38 is recognized for its regulatory role in a spectrum of chronic inflammatory diseases, investigations into its cardiac physiological and pathophysiological functions are nascent. Our aim was to delineate the biological impact of IL-38 in the context of myocardial ischemia–reperfusion injury (MIRI) and to uncover the mechanisms through which it exerts its effects. Methods and ResultsIn this study, we used an MIRI mouse model, LPS/ATP stimulation, and a hypoxia/reoxygenation cell model to determine the regulatory influence of IL-38 on MIRI. We observed that the administration of recombinant IL-38 to mice led to a reduction in infarct size, an enhancement in cardiac function, and a suppression of NLRP3 inflammasome activation. In contrast, genetic deletion of IL-38 was associated with an increase in infarct size, worsening of cardiac function, and upregulation of NLRP3 inflammasome activity. The detrimental effects associated with the absence of IL-38 were mitigated by the administration of a specific NLRP3 inhibitor, suggesting that the inhibition of NLRP3 is a critical component of the protective effect mediated by IL-38 in MIRI. In vitro assays revealed that IL-38 inhibited NLRP3 inflammasome activation in cardiac fibroblasts through the engagement of IL-1R8 and the modulation of SYK phosphorylation. Silencing of IL-1R8 negated the suppressive effect of IL-38 on the NLRP3 inflammasome. ConclusionIL-38 acts as a potent negative regulator of inflammasome activation after MIRI. It achieves this regulatory effect within cardiac fibroblasts by inhibiting SYK phosphorylation, a process mediated by IL-1R8.

A theoretical comprehension of photophysical processes in Cu2+ sensing by 1,7-di(2-pyridyl)bispyrazolo[3,4-b:4′,3′-e]pyridines

Due to its simplicity and sensitivity, metal ion sensing by fluorescent probes has a high biological and ecological impact, and several preliminary applications for Cu2+ have been found. However, the poor understanding of photophysical phenomena by which probes work has led to the growth of unhelpful literature. In this way, 4-aryl-1,7-di(pyridin-2-yl)bispyrazolo[3,4-b:4′,3′-e]pyridines Py2BP2a-c were studied as tridentate ligands in developing the probe Py2BP2a (Ar = Ph, LODCu2+ = 26 nM); thus, this previous work is completed herein by DFT/TD-DFT studies to understand the sensing process. The basal and first excited state of Py2BP2a-c (Ar: Ph, 4-An, 4-Py) and the parent l,4,7-triphenylbispyrazolo[3,4-b:3′,4′-e]pyridine Ph3BP2 were optimised. Results suggest that the probes' fluorescence is due to a twisted intramolecular charge transfer (TICT) and ICT processes around the 4-aryl and 1,7-dipyridin-2-yl groups; likewise, the fluorescence turn-off in the presence of Cu2+ by probe Py2BP2b is due to a photoinduced electron transfer (PET) process, favouring a ligand-to-metal charge transfer (LMCT). These findings enhance our understanding of the sensing process and open new possibilities for its applications in various fields.

Dosimetric and biological impact of activity extravasation of radiopharmaceuticals in PET imaging.

The increasing use of nuclear medicine and PET imaging has intensified scrutiny of radiotracer extravasation. To our knowledge, this topic is understudied but holds great potential for enhancing our understanding of extravasation in clinical PET imaging. This work aims to (1) quantify the absorbed doses from radiotracer extravasation in PET imaging, both locally at the site of extravasation and with the extravasation location as a source of exposure to bodily organs and (2) assess the biological ramifications within the injection site at the cellular level. A radiation dosimetry simulation was performed using a whole-body 4D Extended Cardiac-Torso (XCAT) phantom embedded in the GATE Monte Carlo platform. A 10-mCi dose of 18F-FDG was chosen to simulate a typical clinical PET scan scenario, with 10% of the activity extravasated in the antecubital fossa of the right arm of the phantom. The extravasation volume was modeled as a 5.5mL rectangle in the hypodermal layer of skin. Absorbed dose contributions were calculated for the first two half-lives, assuming biological clearance thereafter. Dose calculations were performed as absorbed doses at the organ and skin levels. Energy deposition was simulated both at the local extravasation site and in multiple organs of interest and converted to absorbed doses based on their respective masses. Each simulation was repeated ten times to estimate Monte Carlo uncertainties. Biological impacts on cells within the extravasated volume were evaluated by randomizing cells and exposing them to a uniform radiation source of 18F and 68Ga. Particle types, their energies, and direction cosines were recorded in phase space files using a separate Geant4 simulation to characterize their entry into the nucleus of the cellular volume. Subsequently, the phase space files were imported into the TOPAS-nBio simulation to assess the extent of DNA damage, including double-strand breaks (DSBs) and single-strand breaks (SSBs). Organ-level dosimetric estimations are presented for 18F and 68Ga radionuclides in various organs of interest. With 10% extravasation, the hypodermal layer of the skin received the highest absorbed dose of 1.32±0.01Gy for 18F and 0.99±0.01Gy for 68Ga. The epidermal and dermal layers received absorbed doses of 0.07±0.01Gy and 0.13±0.01Gy for 18F, and 0.14±0.01Gy and 0.29±0.01Gy for 68Ga, respectively. In the extravasated volume, 18F caused an average absorbed dose per nucleus of 0.17±0.01Gy, estimated to result in 10.58±0.50 DSBs and 268.11±12.43 SSBs per nucleus. For 68Ga, the absorbed dose per nucleus was 0.11±0.01Gy, leading to an estimated 6.49±0.34 DSBs and 161.24±8.12 SSBs per nucleus. Absorbed doses in other organs were on the order of micro-gray (µGy). The likelihood of epidermal erythema resulting from extravasation during PET imaging is low, as the simulated absorbed doses to the epidermis remain below the thresholds that trigger such effects. Moreover, the organ-level absorbed doses were found to be clinically insignificant across various simulated organs. The minimal DNA damage at the extravasation site suggests that long-term harm, such as radiation-induced carcinogenesis, is highly unlikely.

Gut microbiome strain-sharing within isolated village social networks.

When humans assemble into face-to-face social networks, they create an extended social environment that permits exposure to the microbiome of others, thereby shaping the composition and diversity of the microbiome at individual and population levels1-6. Here we use comprehensive social network mapping and detailed microbiome sequencing data in 1,787 adults within 18 isolated villages in Honduras7 to investigate the relationship between network structure and gut microbiome composition. Using both species-level and strain-level data, we show that microbial sharing occurs between many relationship types, notably including non-familial and non-household connections. Furthermore, strain-sharing extends to second-degree social connections, suggesting the relevance of a person's broader network. We also observe that socially central people are more microbially similar to the overall village than socially peripheralpeople. Among 301 people whose microbiome was re-measured 2 years later, we observe greater convergence in strain-sharing in connected versus otherwise similar unconnected co-villagers. Clusters of species and strains occur within clusters of people in village social networks, meaning that social networks provide the social niches within which microbiome biology and phenotypic impact are manifested.

War Exposure and DNA Methylation in Syrian Refugee Children and Adolescents

Exposure to war is associated with poor mental health outcomes. Adverse and traumatic experiences can lead to long-lasting DNA methylation changes, potentially mediating the link between adversity and mental health. To date, limited studies have investigated the impact of war on DNA methylation in children or adolescents, hampering our understanding of the biological impact of war exposure. To identify salivary DNA methylation differences associated with war exposure in refugee children and adolescents. This cohort study included Syrian refugee children and adolescents, and their primary caregiver were recruited from tented settlements in Lebanon. Data collection was carried out in 2 waves, 1 year apart, from October 2017 to January 2018 and October 2018 to January 2019. Children and their caregiver were interviewed, and children provided saliva samples for DNA extraction. Data analysis was conducted in 2022, 2023, and 2024. War exposure assessed by interviewing children and their caregiver using the War Events Questionnaire. Salivary DNA methylation levels were assayed with the Infinium MethylationEPIC BeadChip (Illumina). Epigenetic aging acceleration was estimated using a set of preexisting epigenetic aging clocks. A literature search was conducted to identify previously reported DNA methylation correlates of childhood trauma. The study population included 1507 children and adolescents (mean [SD] age, 11.3 [2.4] years; age range, 6-19 years; 793 female [52.6%]). A total of 1449 children provided saliva samples for DNA extraction in year 1, and 872 children provided samples in year 2. Children who reported war events had a number of differentially methylated sites and regions. Enrichment analyses indicated an enrichment of gene sets associated with transmembrane transport, neurotransmission, and intracellular movement in genes that exhibited differential methylation. Sex-stratified analyses found a number of sex-specific DNA methylation differences associated with war exposure. Only 2 of 258 (0.8%) previously reported trauma-associated DNA methylation sites were associated with war exposure (B = -0.004; 95% CI, -0.005 to -0.003; Bonferroni P = .04 and B = -0.005; 95% CI, -0.006 to -0.004; Bonferroni P = .03). Any war exposure or bombardment was nominally associated with decreased epigenetic age using the Horvath multitissue clock (B = -0.39; 95% CI, -0.63 to -0.14; P = .007 and B = -0.42; 95% CI, -0.73 to -0.11; P = .002). In this cohort of Syrian refugee children and adolescents, war exposure was associated with a small number of distinct differences in salivary DNA methylation.

Diprotonation of taurine: 2-[dihydroxy(oxo)sulfanyliumyl]ethanaminium bis[hexafluoroarsenate(V)

Taurine is part of the cysteine cycle and is one of the few naturally occuring organosulfur-based molecules in the human body. As implied by modern studies, protonated taurine is of biological impact. The first attempts to isolate its protonated species in the binary superacidic system HF/SbF5 were performed by Hopfinger, resulting in the isolation of monoprotonated taurine. Since the chosen conditions seemed rather harsh, investigations in less acidic systems were performed at room temperature to explore the involved protonated species. Herein, we present the structure of 2-[dihydroxy(oxo)sulfanyliumyl]ethanaminium bis[hexafluoridoarsenate(V)], [H2O3SC2H4NH3][AsF6]2, the diprotonated form of 2-aminoethanesulfonic acid (taurine). It was synthesized in the binary superacidic system HF/AsF5 and crystallizes as colourless needles. Diprotonated taurine was structurally characterized by single-crystal X-ray diffraction analysis, low-temperature vibrational spectroscopy and NMR spectroscopy.

Low tristetraprolin expression activates phenotypic plasticity and primes transition to lethal prostate cancer in mice.

Phenotypic plasticity is a hallmark of cancer and increasingly realized as a mechanism of resistance to androgen receptor (AR)-targeted therapy. Now that many prostate cancer (PCa) patients are treated upfront with AR-targeted agents, it's critical to identify actionable mechanisms that drive phenotypic plasticity, to prevent the emergence of resistance. We showed that loss of tristetraprolin (TTP, gene ZFP36) increased NF-κB activation, and was associated with higher rates of aggressive disease and early recurrence in primary PCa. We also examined the clinical and biological impact of ZFP36 loss with co-loss of PTEN, a known driver of PCa. Analysis of multiple independent primary PCa cohorts demonstrated that PTEN and ZFP36 co-loss was associated with increased recurrence risk. Engineering prostate-specific Zfp36 deletion in vivo, induced prostatic intraepithelial neoplasia, and, with Pten co-deletion, resulted in rapid progression to castration-resistant adenocarcinoma. Zfp36 loss altered the cell state driven by Pten loss, demonstrated by enrichment of EMT, inflammation, TNFα/NF-κB, IL6-JAK/STAT3 gene sets. Additionally, our work revealed that ZFP36 loss also induced enrichment of multiple gene sets involved in mononuclear cell migration, chemotaxis, and proliferation. Use of the NF-κB inhibitor, dimethylaminoparthenolide (DMAPT) induced marked therapeutic responses in tumors with PTEN and ZFP36 co-loss and reversed castration resistance.

Leveraging Multi-omics to Disentangle the Complexity of Ovarian Cancer.

To better understand ovarian cancer lethality and treatment resistance, sophisticated computational approaches are required that address the complexity of the tumor microenvironment, genomic heterogeneity, and tumor evolution. The ovarian cancer tumor ecosystem consists of multiple tumors and cell types that support disease growth and progression. Over the last two decades, there has been a revolution in -omic methodologies to broadly define components and essential processes within the tumor microenvironment, including transcriptomics, metabolomics, proteomics, genome sequencing, and single-cell analyses. While most of these technologies comprehensively characterize a single biological process, there is a need to understand the biological and clinical impact of integrating multiple -omics platforms. Overall, multi-omics is an intriguing analytic framework that can better approximate biological complexity; however, data aggregation and integration pipelines are not yet sufficient to reliably glean insights that affect clinical outcomes.

Effect of Biological Therapy for Psoriasis on the Development of Psoriatic Arthritis: A Population-Based Cohort Study.

Evidence comparing the impact of various biologics for psoriasis on the progression to psoriatic arthritis (PsA) is limited. We therefore assessed the risk of PsA associated with interleukin (IL)-23 inhibitor, IL-17 inhibitor, or IL-12/23 inhibitor use compared with tumor necrosis factor (TNF) inhibitor use among patients with psoriasis. This population-based cohort study used the nationwide claims database from South Korea (2007-2023). New users of IL or TNF inhibitors with psoriasis who did not have PsA or other inflammatory arthritis were categorized into each class of the IL inhibitors for comparison with TNF inhibitor users. The outcome measured was the development of incident PsA. We calculated multinomial overlap weights to balance predefined covariates. Hazard ratio (HR) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. We identified 9499 patients with psoriasis (mean age 45.1 years; 33.6% female), of whom 3913 (41.2%), 2126 (22.4%), 2773 (28.8%), and 727 (7.7%) were exposed to IL-23 inhibitor, IL-17 inhibitor, IL-12/23 inhibitor, and TNF inhibitor, respectively. PsA developed in 281 (3.0%) patients during 23,275 person-years. The weighted HR for any IL inhibitors was 0.40 (95% CI 0.25-0.62), with specific HRs of 0.22 (95% CI 0.13-0.37), 0.47 (95% CI 0.28-0.80), and 0.46 (95% CI0.29-0.74) for IL-23 inhibitor, IL-17 inhibitor, and IL-12/23 inhibitor, respectively. IL-23 inhibitors exhibited the greatest rate difference of - 2.61 (95% CI - 3.67 to - 1.55) cases of PsA per 100 person-years. The use of IL inhibitors, particularly IL-23 inhibitors, compared with TNF inhibitors, was associated with a lower risk of developing PsA.

Carbon Nanotubes in Cement-A New Approach for Building Composites and Its Influence on Environmental Effect of Material.

An addition of carbon nanostructures to cement paste is problematic due to the difficulties in obtaining homogenous mixtures. The paper reports on a more effective way of mixing carboxylated multi-walled carbon nanotubes (MWCNT-COOH) in cement pastes. The additional biological impact of the studied nanomodified cement was analyzed in the case of two moss species' vitality. The applied approach of obtaining a homogeneous mixture is based on intense mechanochemical mixing of MWCNT-COOH together with polycarboxylate superplasticizer (SP). As a result, a more homogenous suspension of MWCNT-COOH within a liquid superplasticizer, suitable for addition to hydrophilic cement paste, was obtained. FT-IR/Raman spectroscopy was used for materials' characterization. To explain the mixing process at the molecular level, systematic theoretical studies using density functional theory (DFT) were performed. The structures, interaction energies and IR/Raman vibrational spectra of model carboxylic acids, mixed with functionalized SWCNTs as simplified models of real MWCNTs, were obtained. Due to the controversial opinions on the environmental hazards of carbon nanostructures, additional in vivo studies were performed. In this case, effects of cement modified by the addition of small amounts of MWCNT-COOH with SP in comparison to the composite without carbon nanostructures and control subsoil on the vitality of mosses Polytrichum formosum and Pseudoscleropodium purum were studied.

DNA hypomethylation of INHBA promotes tumor progression and predicts prognosis and immune status of gastric cancer

ObjectiveGastric cancer (GC) is characterized by its high malignancy and poor prognosis. However, the role of Inhibin subunit beta A (INHBA) in GC remains insufficiently understood. This study aims to comprehensively evaluate the clinical significance, biological roles, and possible mechanisms of INHBA in GC.MethodsExpression levels and survival analyses of the Inhibin beta family were assessed using online databases. A prediction model based on INHBA was developed. In addition, the associations between INHBA expression and immune status, and chemotherapy sensitivity were explored. In vitro experiments were conducted to investigate the biological impact of INHBA on GC cells. Pyrosequencing and the DNA methylation inhibitor, 5-AZA-2’-deoxycytidine (5-AZA-dC) were employed to elucidate the mechanisms underlying INHBA function.ResultsOur findings revealed that INHBA exhibited high expression in GC patients, and elevated INHBA expression correlated with worse outcomes. We developed a novel nomogram incorporating INHBA, age, and tumor node metastasis (TNM) stage to predict the prognosis of GC patients. Additionally, INHBA was found to be associated with suppressed infiltration of immune cells and chemosensitivity. Functionally, INHBA promoted the proliferation and invasiveness of GC cells. Mechanistically, pyrosequencing revealed DNA Hypomethylation of INHBA in the first exon region, and the effects of INHBA silencing were rescued by 5-AZA-dC treatment.ConclusionOur study suggests that DNA hypomethylation of INHBA contributes to the progression of GC. Furthermore, INHBA holds promise as a valuable biomarker for prognostic evaluation and immune status prediction in GC patients.

APOE Genotype and Biological Age Impact Inter-Omic Associations Related to Bioenergetics.

Apolipoprotein E ( APOE ) modifies human aging; specifically, the ε2 and ε4 alleles are among the strongest genetic predictors of longevity and Alzheimer's disease (AD) risk, respectively. However, detailed mechanisms for their influence on aging remain unclear. Herein, we analyzed inter-omic, context-dependent association patterns across APOE genotypes, sex, and health axes in 2,229 community-dwelling individuals to test APOE genotypes for variation in metabolites and metabolite-associations tied to a previously-validated metric of biological aging (BA) based on blood biomarkers. Our analysis, supported by validation in an independent cohort, identified top APOE -associated plasma metabolites as diacylglycerols, which were increased in ε2-carriers and trended higher in ε4-carriers compared to ε3-homozygotes, despite the known opposing aging effects of the allele variants. 'Omics association patterns of ε2-carriers and increased biological age were also counter-intuitively similar, displaying increased associations between insulin resistance markers and energy-generating pathway metabolites. These results provide an atlas of APOE -related 'omic associations and support the involvement of bioenergetic pathways in mediating the impact of APOE on aging.

An Introduction to Tertiary Lymphoid Structures in Cancer.

Immunotherapy has revolutionized therapeutics for cancer patients, which signifies the importance of effective antitumor immunity in combatting cancer. However, the benefit of immunotherapies is limited to specific patient populations and tumor types, suggesting the overt need for new immunotherapeutic targets. Tertiary lymphoid structures (TLS) are ectopic lymph node-like structures that develop at the sites of chronic inflammation such as cancer. TLS are correlated with favorable clinical outcomes across multiple solid tumors and are associated with increased tumor-infiltrating lymphocytes (TILs), particularly effector memory CD8+ T cells. Despite strong clinical data in humans, there are still major knowledge gaps on the function of TLS in cancer. Herein, we highlight the known biology and clinical impact of TLS, which offer further evidence to harness TLS for improved immunotherapeutics.

Impact of Individuals' Biological and Meals' Nutritional Characteristics on the Thermic Effect of Food in Humans: Meta-Regression of Clinical Trials.

The thermic effect of food (TEF) may be a therapeutic target for the prevention and treatment of obesity. The impact of different biological and nutritional characteristics on TEF in humans was analyzed. The MEDLINE/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Latin American and Caribbean Health Sciences Literature databases were searched until November 2023 without language restrictions. Clinical trials were included that offered an oral test meal to adult and elderly individuals in a fasting state and measured TEF using calorimetry. The average TEF of each group was the outcome, and the impact of the individuals' and meal characteristics on the TEF was assessed using subgroups, meta-regression, and compositional analysis. The review included 133 studies, with 321 different groups. The mean TEF at 60 minutes after the test meal was 262 (95% CI, 236-288) kcal/d and decreased over time until 240 minutes after the test meal (P < .01). Male participants, individuals with normal body mass index, meals with energy content offered according to individual requirements, and meals with a mixed degree of food processing yielded a higher TEF. The total energy content of meals was the variable most strongly associated with TEF. Compositional analysis showed that the amount of lipids in meals was the only macronutrient consistently and negatively associated with TEF. The TEF is influenced by specific individuals' and meal characteristics. Total energy content and the amount of lipids were the characteristics of the meals most consistently associated with TEF. However, due to important methodological differences between studies, it is difficult to determine how to use TEF as a potential therapeutic target against obesity. PROSPERO registration no. CRD42023432504.

МЕДИКО-БІОЛОГІЧНІ ОСНОВИ ВПЛИВУ ФІЗИЧНИХ ВПРАВ НА ЗБЕРЕЖЕННЯ ЗДОРОВ’Я СТУДЕНТСЬКОЇ МОЛОДІ

The article examines the medical and biological basis of the influence of physical exercises on the health of student youth. Literary sources related to the topic of the study were analyzed. The problem is described in its general form, which concerns the way of life of modern student youth. It is noted that only in-depth knowledge of the medical and biological influence will help to form students' desire and motivation to engage in physical exercises, as well as to observe the basics of a healthy lifestyle. The morpho-functional changes occurring in the human body during physical exercises are revealed. The division of the organism's reserves into biological and social is presented. The functional effects of exercises on life expectancy is described. A comparative analysis of the influence of motor activity and hypokinesia on the human body was carried out. The basics of adaptation of individual body systems to physical exertion are revealed, namely: changes in the composition and physicochemical properties of blood and the circulatory system, functional effects of adaptation of the respiratory system, features of adaptation of the digestive and metabolic systems, as well as functional effects of adaptation of neurohumoral regulation systems. In the process of research, it was concluded that it is difficult to overestimate the medical and biological impact of physical exercises on the process of preserving the health of student youth, since physical activity affects the human body in a complex way, on all its systems, processes of exchange and accumulation of functional reserves. It was concluded that with the help of physical exercises you can achieve many positive effects and affect the overall life expectancy of a person. Prospects for further research in this direction are seen in determining the level of awareness of student youth in the issues of medical and biological bases of the influence of physical exercises on preserving their own health, as well as finding new approaches for working with students in this direction in order to achieve the formation of sustainable motivation for physical activities exercises and adherence to the basics of a healthy lifestyle.

MCM4 Promotes the Progression of Malignant Melanoma by Activating the PI3K/AKT Pathway.

This study aims to elucidate the role of minichromosome maintenance protein 4 (MCM4) in malignant melanoma (MM) and explore the underlying mechanism. Initially, data from The Cancer Genome Atlas (TCGA) database and the Molecular Signature Database (MSigDB) were used to investigate the biological impact of MCM4 on MM. Further, a prognostic model using Cox regression analysis was developed to predict the overall survival (OS) rate in the MM patients. The effects of MCM4 on the proliferation, migration, and invasion abilities of MM (B16F0 and A375) cells were demonstrated using the CCK-8, colony formation, EDU, wound scratch, and Transwell assays. In subcutaneous tumor models in C57BL/6 mice invivo, the expression levels of MCM4 in MM cells and tumors were detected using Western blot and immunofluorescence approaches. The bioinformatics analysis indicated that MCM4 was expressed higher in MM tissues than in the normal tissues (p < 0.05). The established OS prediction model could significantly contribute to devising follow-up strategies and treating MM patients. MCM4 knockdown resulted in reduced proliferation, migration, and invasion abilities of MM cells, which were reversed by MCM4 overexpression (p < 0.05). Moreover, MCM4 could activate the phosphatidylinositol 3'-kinase (PI3K)/AKT pathway in MM cells. The PI3K inhibitor (LY294002) could reverse the effects of MCM4 on MM cells. MCM4 could substantially prompt the tumor growth of MM in mice through the PI3K/AKT pathway invivo. In summary, MCM4 prompted the development and metastasis of MM by activating the PI3K/AKT pathway.

Thermomechanobiology as a new research field in soft tissues

During intense galloping, the difference in temperature between the external and the central part of an equine superficial digital flexor tendon can be as high as 7°C. Thirty minutes of jogging modifies the temperature in human knee cartilage from 32°C to 37°C. Intrinsic dissipative phenomena related to the viscoelastic behavior of soft tissues have been identified to be primarily responsible for the observed temperature increase, a situation referred to as self-heating in mechanics. While a 5°C increase may be considered negligible from a mechanical point of view in the cartilage at first sight, it can have a significant biological impact. It has been recently proposed that self-heating and the resulting increase of temperature in cartilage following mechanical stimulation can be necessary for its maintenance. This new concept complements the general acceptance that mechanobiology is central to the homeostasis of musculoskeletal tissues. In most biomechanical and biological studies on cartilage or other soft tissues, the temperature is set at 37°C and considered constant, despite human knee cartilage at rest being around 32°C, for example. Therefore, there is a deficit of information on the role and effect of physiological temperature variation induced through mechanical loading in soft tissues, opening a new research avenue that we coin thermomechanobiology.

Microfocused Ultrasound in Regenerative Aesthetics: A Narrative Review on Mechanisms of Action and Clinical Outcomes.

Microfocused ultrasound with visualization (MFU-V) is widely used in aesthetic medicine for skin tightening and rejuvenation. However, its role in regenerative aesthetics and its precise mechanism of action are not fully understood. This narrative review aims to contextualize and articulate the mechanism of action of MFU-V, evaluate its role in regenerative aesthetics, and assess its effectiveness based on existing clinical, histological, and skin-mechanical studies. A comprehensive literature search was performed to collect and analyze studies on MFU's biological mechanisms, clinical outcomes, and impact on extracellular matrix (ECM) regeneration. The review integrates findings from clinical trials, histological analyses, and biomechanical assessments to provide a cohesive understanding of MFU-V's role in aesthetic medicine. MFU-V emits focused ultrasound energy that penetrates multiple skin layers and the superficial musculoaponeurotic system, creating localized thermal coagulation points. These points initiate biological responses that recruit fibroblasts and stimulate the production of new collagen and elastin fibers. Enhanced ECM protein synthesis leads to significant improvements in skin biomechanics and quality, reducing skin laxity and enhancing appearance. Clinical studies support these findings, showing improvements in skin firmness and texture following MFU-V treatment. Through analyzing the underlying biological mechanisms and the observable clinical outcomes, this narrative review sets the stage for a comprehensive understanding of the mechanism of action and role of MFU-V in regenerative aesthetics.