Biological Effects Research Articles

Study of Azobenzene-modified Black Phosphorus for Potential Tumor Therapy.

Exploring the interaction between black phosphorus (BP)-based hybrid systems and target proteins is of great significance for understanding the biological effects of 2D nanomaterials at the molecular level. Density functional theory (DFT) calculations revealed that different terminal groups of the azobenzene (AB) motif in BP@AB hybrids can affect the extent of interfacial charge transfer between the BP sheet and AB-derivatives, which determines the electrostatic interaction with proteins and hence biofunctions of BP@AB hybrids. With the advantage of AB modification, BP@AB hybrids displayed antitumor effects and induced production of cellular reactive oxygen species and apoptosis in cancer cells. Through the proteomics profiling, cellular ribosome and lipid metabolic processes were screened out as the target pathways of the BP@AB-NH2 in HeLa cells, while the BP@AB-S-S-AB system mainly targets the ERBB and PPAR signaling pathways. Molecular docking simulations revealed that due to the positive charge, ribosomal pathway proteins enriched in negatively charged amino acids such as lysine and arginine are preferentially adsorbed and bound by BP@AB-NH2 hybrids. Whereas for BP@AB-S-S-AB, receptors containing narrow and long pocket domains are more likely to bind with BP@AB-S-S-AB by van der Waals forces for the rod-like hybrids. Different biomolecule targeting and action modes of BP@AB hybrids have been rationalized by different electrostatic environments and matching of geometric configurations, shedding insight for designing efficient and targeted modification of a 2D nanomaterial-based strategy for cancer therapy.

Comprehensive Insight into Green Synthesis Approaches, Structural Activity Relationship, and Therapeutic Potential of Pyrazolic Chalcone Derivative.

Pyrazolic chalcone exhibits diverse therapeutic activities, including anti-inflammatory, antioxidant, antimicrobial, antitumor, and anti-diabetic properties. Structural activity relationship (SAR) studies play a crucial role in understanding the molecular aspects governing their biological effects, guiding the rational design of derivatives with enhanced efficacy and reduced side effects. This review provides an overview of pyrazolic chalcone derivatives, emphasizing their synthesis through both conventional and green methods. In comparison, conventional synthesis methods have been widely employed in the past for the production of pyrazolic chalcones, often relying on traditional chemical processes that may involve the use of hazardous reagents and generate significant waste. On the other hand, green synthesis methods, in harmony with the growing emphasis on sustainable practices in drug discovery, offer a more environmentally friendly alternative. Green synthesis typically involves the use of eco-friendly reagents, solvents, and energy-efficient processes, resulting in reduced environmental impact and improved resource efficiency. Overall, pyrazolic chalcone derivatives represent a promising class of compounds with significant potential for therapeutic applications.

The role of probiotics in maintaining vaginal ecosystem

A disturbed vaginal ecosystem is characterized by reduced or non-existing lactobacillary flora and damaged vaginal epithelium. It may not always be apparent whether alterations of the vaginal epithelium or pathogenic microorganisms are the primary cause of a disturbed vaginal ecosystem. Estriol plays a key role in developing and maintaining a healthy vaginal epithelium, stimulating cell growth and differentiation, increases epithelial thickness, and also promotes glycogen synthesis, which is required to maintain an acidic environment. Estriol deficiency results in the vulvovaginal atrophy and the development of atrophic vaginitis. In turn, Lactobacillus acidophilus maintains a healthy microbiome, protecting against infections and creating an acidic environment unfavourable for the growth of pathogens. In recent years, an increasing interest has been developed in probiotics with the belief that probiotics could be able to restore the vaginal microbiota health. A review of scientific articles on the use of an ultra-low-dose vaginal estriol 0.03 mg in combination with Lactobacillus acidophilus to normalize the vaginal microbiota and treat vaginal infections has been conducted. An analysis of published clinical studies and meta-analyses on the use of probiotics in vaginal infections showed the mechanisms of action of probiotics, their biological role and clinical effects. The integration of probiotics into the treatment and prevention of bacterial vaginosis is growing more urgent. The results of numerous studies and meta-analyses confirmed their high efficacy and safety. The supplementation of standard antibiotic therapy with probiotics improves cure rates, restores normal vaginal microflora and reduces the risk of relapse. Therefore, further studies on the use of probiotics to develop more effective and personalized treatment strategies providing long-term results are needed. The publication of new evidence will make it possible to introduce best practices into clinical practice and ensure a healthier future for patients worldwide.

Patient-centred composite scores as tools for assesment of response to biological therapy for paediatric and adult severe asthma.

We have previously developed Core Outcome Measures sets for Severe Asthma (COMSA) by multi-stakeholder consensus. There are no patient-centred tools to quantify response to biologics for severe asthma. We aimed to develop paediatric and adult CompOsite iNdexes For Response in asthMa (CONFiRM) incorporating clinical parameters and patient-reported quality of life (QoL). International expert healthcare professionals (HCPs) and patients with severe asthma were invited to: 1) develop consensus levels of clinically relevant changes for each outcome measure within COMSA; 2) use multicriteria decision analysis to develop the CONFiRM scores and 3) assess their internal validity. A separate group of HCPs evaluated CONFiRM's external validity. Five levels of change for each COMSA outcome were agreed. Severe exacerbations and maintenance oral corticosteroids use were rated as most important in determining both paediatric and adult CONFiRM scores. There was strong agreement between HCPs and patients, although patients assigned greater importance to QoL. The CONFiRM score quantified response to a biological from -31 (deterioration) to 69 (best possible response). Paediatric and adult CONFiRMs had good discriminative ability for a sufficient (AUC≥0.92) and a substantial (AUC≥0.95) response to biologics. Both CONFiRMs demonstrated excellent external validity (Spearman correlation coefficients 0.9 and 0.8 for paediatric and adult respectively (p<0.0001)). We have developed novel patient-centred paediatric and adult CONFiRMs which include QoL measures. CONFiRMs should allow a more holistic understanding of response for the patient and a standardised assessment of the effectiveness of biologics between studies. Further research is needed to prospectively validate CONFiRM scores.

Screening of Optimal Phytoconstituents through in silico Docking, Toxicity, Pharmacokinetic, and Molecular Dynamics Approach for Fighting against Polycystic Ovarian Syndrome.

Polycystic ovarian syndrome (PCOS) is a hormonal disorder caused by excessive secretion of male sex hormones in females. Herbal remedies for PCOS are lightning up as they bypass the adverse effects and are profoundly safe on prolonged usage. The present study included a selection of 34 herbs pursuing biological effects on the uterus, and their major chemical constituents were subjected to a series of in silico techniques using different software. The proteins contributing majorly to the hormonal functions like Human cytochrome P450 CYP17A1 (3RUK), Progesterone (1E3K), and estrogen receptor (1X7R) were selected for the study. Molecular docking studies were performed using AutoDock 1.5.7. The pharmacokinetic properties were predicted using the SwissADME online tool, while toxicity parameters were assessed with OSIRIS toxicity explorer and pkCSM. Molecular dynamics simulations and free energy calculations were performed using the Schrödinger suite. Constituents with a basic steroidal nucleus demonstrated high binding energy values. An analysis of all the in silico techniques showed that Sarsasapogenin from Asparagus racemosus exhibited strong binding energies of -10.88 kcal/mol, -10.51 kcal/mol, and -9.79 kcal/mol with the selected specific proteins. In molecular dynamics simulations, Sarsasapogenin displayed ideal stability, with RMSD fluctuations below 3 Å and RMSF slightly higher than the corresponding peak of apoprotein. Additionally, it showed a favorable druglikeness profile and non-toxic effects across all screened parameters. From the list of the selected constituents, sarsasapogenin was found to be ideal, and further research on it for targeting PCOS is expected to yield promising results.

Antioxidant activity and content of total phenols and flavonoids of aqueous extracts from leaves of Pistacia lentiscus L.

The Mounts of Tessala (western of Algeria) is a remarkable site of plants diversity, characterized by the presence of numerous aromatic and medicinal species used by the local population as therapeutic agents, the mastic tree (Pistacia lentiscus L.) is among the plants inhabiting this mountain; it is a perennial shrub belonging to the family Anacardiaceae. The dosage of some polyphenols (total phenols, flavonoids) varied respectively between 21.20 - 98.23 mg gallic acid equivalents/g and 39.767 - 91.288 mg catechin equivalents/g. ANOVA revealed a significant variation in the mean concentrations according to the used extract. Evaluation of the antioxidant power of aqueous extracts has revealed a remarkable biological effect. The high inhibition percentages (100%) were found in the decocted extract at 10 mg/mL, followed by the macerated extract at 10 mg/mL, and finally the infused extract with 82.99% at 20 mg/mL. The DPPH free radical scavenging test revealed that the antioxidant activity of aqueous extracts varied significantly according to extract type and its concentration. The results obtained not only confirm the richness of active principles in the studied plant but also its therapeutic effectiveness.

Ascorbic acid regulates in vitro and in vivo toxicogenetic effects of hydroxyurea on eukaryotic cells

Hydroxyurea (HU) exerts unique and diverse biological effects as an anti-leukemic agent, irradiation sensitizer, and HbS inducer in patients with sickle cell anemia. Herein, we assessed the potential toxicogenic and/or oxidant effects of hydroxyurea associated with ascorbic acid by in vivo examinations in Allium cepa and human cancer cells and systemically on mice tissues. Growing A. cepa roots and HCT-116 colorectal tumor cells were examined after HU and HU plus ascorbic acid exposure. DNA damage and antioxidant enzymatic activity were quantified in peripheral blood mononuclear cells (PBMC), bone marrow leukocytes and livers of mice after 7 day-HU treatment (7.5, 15 and 30 mg/kg/day) and Vitamin C 2 μM. Hydroxyurea presented toxic effects on meristematic Allium cepa cells, causing chromosomal abnormalities and reduction of mitotic index, killed HCT-116 colorectal carcinoma cells and induced DNA injuries upon mice cells (hepatocytes, bone marrow leukocytes and PBMC). Simultaneously, hydroxyurea decreased levels of CAT and GSH activities and expand lipid peroxidation. All these biochemical and physiological changes were ameliorated when associated with ascorbic acid, indicating it restored antioxidant enzymes, decreased MDA levels, removed peroxides and, consequently, presented cytoprotection against HU-provoked cellular damage in normal cells. On the other hand, antioxidants compounds may interfere on effectiveness of HU during anticancer chemotherapies.

Evaluation of the Biological Effect of a Nicotinamide-Containing Broad-Spectrum Sunscreen on Photodamaged Skin.

UVA-UVB increases skin matrix metalloproteinases and breaks down extracellular proteins and fibrillar type1 collagen, leading to photodamage. Topical application of nicotinamide prevents UV-induced immunosuppression. Several studies have demonstrated the importance of protection against UV. This study aims to determine the biological effect of a high broad-spectrum UVB-UVA sunscreen containing nicotinamide and panthenol (SSNP) on photodamaged skin using linear confocal optical coherence tomography (LC-OCT), immunohistochemistry, and RNA profiling. Two areas of severely photodamaged forearm skin (L01 and L02) and one less sun-damaged (naturally protected) area on the inner part of the forearm (L03) were identified in 14 subjects. These areas were imaged using LC-OCT and L01 and L03 were biopsied at baseline. After 4weeks of treatment with SSNP, L02 was reimaged using LC-OCT, and biopsied. Histology, immunostaining with p21, p53, PCNA, and CPD, and RNA sequencing were performed in all samples. LC-OCT analysis showed that epidermis thickness and the number of keratinocytes is higher in the sun-exposed areas than in the non-exposed areas. Comparing before and after treatment, even though there is a trend towards normalization, the differences were not statistically significant. The expression of p21, PCNA, p53, and CPD increased in severely photodamaged skin compared to less-damaged skin. When comparing before and after treatment, only p21 showed a trend to decrease expression. RNA sequencing analysis identified 1552 significant genes correlating with the progression from non-visibly photodamaged skin to post-treatment and pre-treatment samples; in the analysis comparing pre- and post-treatment samples, 5429 genes were found to be significantly associated. A total of 1115 genes are common in these two analyses. Additionally, nine significant genes from the first analysis and eight from the second are related to collagen. Six of these collagen genes are common in the two analyses. MAPK and cGMP-PKG signalling pathways are upregulated in the progression to photodamage analysis. In the pre- and post-treatment analysis, 32 pathways are downregulated after treatment, the most statistically significant being the ErbB, Hippo, NOD-like receptor, TNF, and NF-kB signalling pathways. This study demonstrates the role of SSNP in collagen generation, highlights the relevance of the cGMP-PKG and MAPK signalling pathways in photodamage, and shows the ability of SSNP to downregulate pathways activated by UV exposure. Additionally, it deepens our understanding of the effect of SSNP on immune-related pathways.

Behavioural and neuronal substrates of serious game-based computerised cognitive training in cognitive decline: randomised controlled trial.

Investigations of computerised cognitive training (CCT) show heterogeneous results in slowing age-related cognitive decline. To comprehensively evaluate the effectiveness of serious games-based CCT, integrating control conditions, neurophysiological and blood-based biomarkers, and subjective measures. In this bi-centric randomised controlled trial with parallel groups, 160 participants (mean age 71.3 years) with cognitive impairment ranging from subjective decline to mild cognitive impairment, were pseudo-randomised to three arms: an intervention group receiving CCT immediately, an active control (watching documentaries) and a waitlist condition, which both started the CCT intervention after the control period. Both active arms entailed a 3-month intervention period comprising a total of 60 at-home sessions (five per week) and weekly on-site group meetings. In the intervention group, this was followed by additional 6 months of CCT, with monthly booster sessions to assess long-term training effects. Behavioural and subjective changes were assessed in 3-month intervals. Biological effects were measured by amyloid blood markers and magnetic resonance imaging obtained before and after training. Adherence to the training protocol was consistently high across groups and time points (4.87 sessions per week). Domain-specific cognitive scores showed no significant interaction between groups and time points. Significant cognitive and subjective improvements were observed after long-term training. Voxel-based morphometry revealed no significant changes in grey matter volume following CCT, nor did amyloid levels moderate its effectiveness. Our study demonstrates no benefits of 3 months of CCT on cognitive or biological outcomes. However, positive effects were observed subjectively and after long-term CCT, warranting the inclusion of CCT in multicomponent interventions.

Chemical Profile of Kumquat (Citrus japonica var. margarita) Essential Oil, In Vitro Digestion, and Biological Activity

Kumquat is one of the smallest citrus fruits (from the Rutaceae family), and its essential oil’s biological effects have not yet been sufficiently researched, in contrast to the essential oils of its relatives. Therefore, the aim of this large-scale study was to investigate the chemical profile of kumquat essential oils (KEOs) isolated by microwave-assisted distillation (MAD) and Clevenger hydrodistillation using GC-MS analysis. To test the bioaccessibility of their bioactive components, in vitro digestion with commercially available enzymes was performed. The final step of this research was to test their cytotoxic activity against a cervical cancer cell line (HeLa), a human colon cancer cell line (HCT116), a human osteosarcoma cell line (U2OS), and a healthy cell line (RPE1). Two methods were used to test the antioxidant activity: DPPH (2,2-diphenyl-1-picrylhydrazyl) and ORAC (oxygen radical absorbance capacity). The antibacterial activity was tested in relation to the growth and adhesion of Escherichia coli and Staphylococcus aureus on a polystyrene surface. The GC-MS analysis showed that the major compound in both kumquat essential oils was limonene, which was stable before and after in vitro digestion (&gt;90%). The results showed that the cytotoxic activity of the KEOs in all three cancer cell lines tested was IC50 1–2 mg/mL, and in the healthy cell line (RPE1), the IC50 value was above 4 mg/mL. The antibacterial activity of the KEOs obtained after MAD and Clevenger hydrodistillation was 4 mg/mL against E. coli and 1 mg/mL against S. aureus. The KEOs after MAD and Clevenger hydrodistillation reduced the adhesion of E. coli by more than 1 log, while there was no statistically significant effect on the adhesion of S. aureus to the polystyrene surface. Both KEOs exhibited comparable levels of antioxidant activity using both methods tested, with IC50 values of 855.25 ± 26.02 μg/mL (after MAD) and 929.41 ± 101.57 μg/mL (after Clevenger hydrodistillation) for DPPH activity and 4839.09 ± 91.99 μmol TE/g of EO (after MAD) and 4928.78 ± 275.67 μmol TE/g of EO (after Clevenger hydrodistillation) for ORAC. The results obtained show possible future applications in various fields (e.g., in the food, pharmaceutical, cosmetic, and agricultural industries).

MiR-19b-3p inhibits cell viability and proliferation and promotes apoptosis by targeting IGF1 in KGN cells

Background Endometriosis (EM) is a major cause of infertility, but the pathogenesis and mechanisms are not yet fully elucidated. MiR-19b-3p is involved in many diseases, but its functional role in EM-associated infertility remains unexplored. This study aimed to examine miR-19b-3p abundance and IGF1 concentration in cumulus cells (CCs) and follicular fluid of EM-associated infertility patients, and to investigate the potential role of miR-19b-3p in KGN cells by identifying its target and elucidating the underlying mechanisms. Results The results from the case-control study indicated that, compared to the control group consisting of patients with tubal infertility, patients with EM-associated infertility exhibited a lower percentage of mature oocytes. MiR-19b-3p level was elevated in CCs from EM-associated infertility patients. IGF1 was identified as a direct target of miR-19b-3p and was negatively regulated by miR-19b-3p in KGN cells. Overexpression of miR-19b-3p significantly inhibited cell viability and proliferation, promoted apoptosis, and arrested the cell cycle at G0/G1 phase in KGN cells. The effects of miR-19b-3p were reversed by co-transfection of IGF1, and the biological effects of miR-19b-3p in KGN cells were mediated by IGF1. Additionally, miR-19b-3p targeted IGF1 to down-regulate AKT phosphorylation and participate in the apoptotic pathway in KGN cells. Conclusions This study demonstrates that miR-19b-3p level is elevated in CCs and IGF1 concentration is decreased in follicular fluid in patients with EM-associated infertility. MiR-19b-3p regulates the biological effects of KGN cells by targeting IGF1.

Composite Scaffold Materials of Nanocerium Oxide Doped with Allograft Bone: Dual Optimization Based on Anti-Inflammatory Properties and Promotion of Osteogenic Mineralization.

Spinal fusion technique is widely used in the treatment of lumbar degeneration, cervical instability, disc injury, and spinal deformity. However, it is usually accompanied by a high incidence of fusion failure and pseudoarthrosis, placing higher demands on bone implants. Therefore, materials with good biocompatibility, osteoconductivity, and even induce bone ingrowth, which can be used to improve spinal fusion rate and bone regeneration, have become a hot research topic. Here, ultra-small cerium oxide nanoparticles (CeO2 NPs) are prepared and loaded onto the surface of the homograft bone surface to prepare a composite scaffold AB@PLGA/CeO2. The composite scaffold shows the competitive ability to promote osteoblast differentiation in vitro. In vivo experiments show that AB@PLGA/CeO2 has a good bone enhancement effect. In particular, good biological effects of collagen fiber formation, osteogenic mineralization, and tissue repair are shown in intervertebral implant fusion. Further, transcriptome sequencing confirms that CeO2 NPs promote osteogenic differentiation and mineralization by regulating extracellular matrix (ECM) and collagen formation. Meanwhile, CeO2 NPs can regulate the function of the PI3K-Akt signaling pathway to exert its ability to promote osteogenic differentiation and mineralization and affect p53 and cell cycle signaling pathway to regulate osteogenic differentiation and mineralization. Hence, the proposed scaffold is a promising strategy for intervertebral fusion in the clinic.

A novel ITGB8 transcript variant sustains ovarian cancer cell survival through genomic instability and altered ploidy on a mutant p53 background

BackgroundTranscript variants and protein isoforms are central to unique tissue functions and maintenance of homeostasis, in addition to being associated with aberrant states such as cancer, where their crosstalk with the mutated tumor suppressor p53 may contribute to genomic instability and chromosomal rearrangements. We previously identified several novel splice variants in ovarian cancer RNA-sequencing datasets; herein, we aimed to elucidate the biological effects of the Integrin Subunit Beta 8 variant (termed pITGB8-205).MethodsResolution of the full-length sequence of pITGB8-205 through rapid amplification of cDNA ends (RACE-PCR). Cell cycle analysis and karyotype studies were performed to further explore genomic instability. RNA-seq and proteomics analyses were used to identify the differential expression of the genes.ResultsThis full-length study revealed a unique 5’ sequence in pITGB8-205 that differed from the reported ITGB8-205 sequence, suggesting differential regulation of this novel transcript. Under a p53 mutant background, overexpression of pITGB8-205 triggered genetic instability reminiscent of oncogene-induced replicative stress with extensive abnormal mitoses and chromosomal and nuclear aberrations indicative of chromosomal instability, leading to near whole-genome duplication that imposes energy stress on cellular resources. Micronuclei and aneuploidy are striking features of pITGB8-205-overexpressing p53-mutant cells but are not enhanced in p53 wild-type (WT) cells. RNA-seq and proteomics analyses further suggested that p53 inactivation in ovarian cancer provides a permissive intracellular molecular niche for pITGB8-205 to mediate its effects on genomic instability. This observation is pivotal considering that most high-grade serous ovarian carcinoma (HGSC) tumors express mutant p53. The resulting aneuploid clones with enhanced self-renewal and survival capabilities disrupt clonal dominance under stress yet maintain a balance between replicative stress and prosurvival advantages.ConclusionpITGB8-205-overexpressing clones sustain ovarian tumor cell survival, achieve homeostasis and are formidable opponents of therapy.

Divergent Molecular Responses to Heavy Water in Arabidopsis thaliana Compared to Bacteria and Yeast

Heavy water (D2O) is scarce in nature, and despite its physical similarity to water, D2O disrupts cellular function due to the isotope effect. While microbes can survive in nearly pure D2O, eukaryotes such as Arabidopsis thaliana are more sensitive and are unable to survive higher concentrations of D2O. To explore the underlying molecular mechanisms for these differences, we conducted a comparative proteomic analysis of E. coli, S. cerevisiae, and Arabidopsis after 180 min of growth in a D2O-supplemented media. Shared adaptive mechanisms across these species were identified, including changes in ribosomal protein abundances, accumulation of chaperones, and altered metabolism of polyamines and amino acids. However, Arabidopsis exhibited unique vulnerabilities, such as a muted stress response, lack of rapid activation of reactive oxygen species metabolism, and depletion of stress phytohormone abscisic acid signaling components. Experiments with mutants show that modulating the HSP70 pool composition may promote D2O resilience. Additionally, Arabidopsis rapidly incorporated deuterium into sucrose, indicating that photosynthesis facilitates deuterium intake. These findings provide valuable insights into the molecular mechanisms that dictate differential tolerance to D2O across species and lay the groundwork for further studies on the biological effects of uncommon isotopes, with potential implications for biotechnology and environmental science.

Poly-Amino-β-Cyclodextrin Microparticles for the Reduction of Xenobiotics and Emerging Contaminants, Including Pharmaceuticals, from the Natural Environment

The contamination of the natural environment by xenobiotics and emerging contaminants, including pharmaceuticals, poses significant risks to ecosystems and human health. Among these contaminants, hormones and pharmaceutical compounds are particularly concerning due to their persistence and potential biological effects even at low concentrations. In this study, we investigated the efficacy of poly-amino-β-cyclodextrin (PA-β-CD) microparticles in adsorbing and reducing specific xenobiotics and pharmaceuticals from aqueous solutions. Our research focused on four contaminants: two hormones, testosterone and progesterone, and two pharmaceutical drugs, diclofenac and carbamazepine. High-performance liquid chromatography (HPLC) was employed to quantify the adsorption capacity and efficiency of PA-β-CD microparticles.

Correction: Li et al. Isolation and Identification of a Tibetan Pig Porcine Epidemic Diarrhoea Virus Strain and Its Biological Effects on IPEC-J2 Cells. Int. J. Mol. Sci. 2024, 25, 2200

There was an error in the original publication [...]

Biological effects of combinations of structurally diverse human milk oligosaccharides

Human milk oligosaccharides (HMOs) are a diverse group of structures and an abundant bioactive component of breastmilk that contribute to infant health and development. Preclinical studies indicate roles for HMOs in shaping the infant gut microbiota, inhibiting pathogens, modulating the immune system, and influencing cognitive development. In the past decade, several industrially produced HMOs have become available to fortify infant formula. Clinical intervention trials with manufactured HMOs have begun to corroborate some of the physiological effects reported in preclinical studies, especially modulation of the gut microbiota in the direction of breastfed infants. As more HMOs become commercially available and as HMOs have some shared mechanisms of action, there is a need to better understand the unique and differential effects of individual HMOs and the benefits of combining multiple HMOs. This review focuses on the differential effects of different HMO structural classes and individual structures and presents a scientific rationale for why combining multiple structurally diverse HMOs is expected to exert greater biological effects.

Asthma and COVID-19: Unveiling Outcome Disparities and Treatment Impact Based on Distinct Endotypes.

Epidemiologic studies on asthmatics and in vitro data suggest a protective role of T2 inflammation in SARS-CoV-2 infection. Using a large, multisite cohort, we studied clinical outcomes following SARS-CoV-2 infection in multiple asthma endotypes and examined the effects of T2-directed biologics in infected asthmatics.in Methods: The National COVID Cohort Collaborative (N3C) Data Enclave was used to identify and stratify asthmatic patients by endotype to include non-T2 and T2 asthmatics, as well as exposure to T2-directed biologic therapy. We evaluated the risk of hospitalization, invasive mechanical ventilation, and 90-day mortality by endotype and exposure to biologics. For this study, 402,376 patients met inclusion criteria, of which 138,142 (34%) were characterized as non-T2 and 264,234 (66%) as T2 asthmatics, a group further divided into 104,823 (26%) atopic, 84,440 (21%) eosinophilic, and 74,971 (19%) T2-high asthmatic endotypes. Compared to non-T2 asthmatics, atopic and T2-high asthmatics experienced decreased odds of hospitalization, and 90-day mortality. Conversely, eosinophilic asthmatics experienced higher odds of hospitalization, intubation, and 90-day mortality. Exposure to T2-directed biologic therapies did not alter outcomes after propensity score matching. In contrast, maximum eosinophil count and recent systemic corticosteroid use were directly correlated with increased odds of all outcomes. COVID-19 outcomes differ depending on asthma endotype, with atopic asthmatics experiencing lower odds and eosinophilic asthmatics experiencing higher odds of deleterious outcomes. T2-directed biologic treatment did not alter these outcomes but recent systemic corticosteroid use predisposes all asthmatics patients to adverse outcomes. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Neddylation of protein, a new strategy of protein post-translational modification for targeted treatment of central nervous system diseases

Neddylation, a type of protein post-translational modification that links the ubiquitin-like protein NEDD8 to substrate proteins, can be involved in various significant cellular processes and generate multiple biological effects. Currently, the best-characterized substrates of neddylation are the Cullin protein family, which is the core subunit of the Cullin-RING E3 ubiquitin ligase complex and controls many important biological processes by promoting ubiquitination and subsequent degradation of various key regulatory proteins. The normal or abnormal process of protein neddylation in the central nervous system can lead to a series of occurrences of normal functions and the development of diseases, providing an attractive, reasonable, and effective targeted therapeutic strategy. Therefore, this study reviews the phenomenon of neddylation in the central nervous system and summarizes the corresponding substrates. Finally, we provide a detailed description of neddylation involved in CNS diseases and treatment methods that may be used to regulate neddylation for the treatment of related diseases.

E-cigarettes and vaping, new spotlight on smoking as an old cardiovascular risk factor?

Smoking is one of the leading causes of chronic non-communicable diseases and asignificant risk factor for cardiovascular and respiratory diseases. While global tobacco consumption has decreased over the past two decades, the use of e‑cigarettes and water pipes (shisha) has surged at an alarming rate, particularly among younger individuals. E‑cigarettes do not offer acompletely risk-free alternative to traditional cigarettes, as the vast array of flavors and ease of use contribute to agrowing number of dependent users. Furthermore, they are not necessarily effective in overcoming nicotine addiction. This contribution provides an overview of the cardiovascular health impacts associated with shisha smoking and e‑cigarette vaping, with aparticular emphasis on the detrimental effects on endothelial function. The harmful biological effects of the toxic substances in these products, especially oxidative stress and inflammatory responses, are also discussed. Finally, the current state of recommendations, legal regulations, and commercial advertising are summarized.