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Crosstalk between hypoxia-induced pyroptosis and immune escape in cancer: From mechanisms to therapy
No full textPyroptosis can be triggered through both canonical and non-canonical inflammasome pathways, involving the cleavage of gasdermin (GSDM) protein family members, like GSDMD and GSDME. The impact of pyroptosis on tumors is nuanced, because its role in regulating cancer progression and anti-tumor immunity may vary depending on the tumor type, stage, location, and immune status. However, pyroptosis cannot be simply categorized as promoting or inhibiting tumors based solely on whether it is acute or chronic in nature. The interplay between pyroptosis and cancer is intricate, with some evidence suggesting that chronic pyroptosis may facilitate tumor growth, while the acute induction of pyroptosis could stimulate anti-cancer immune responses. Tumor hypoxia activates hypoxia inducible factor (HIF) signaling to modulate pyroptosis and immune checkpoint expression. Targeting this hypoxia-pyroptosis-immune escape axis could be a promising therapeutic strategy. This review highlights the complex crosstalk between hypoxia, pyroptosis, and immune evasion in the TME
Identification of hub genes and pathways in Uterine corpus endometrial carcinoma (UCEC): A comprehensive in silico study
No full textBackground: Uterine corpus endometrial carcinoma (UCEC), derived from the endometrium, is the most common type of endometrial malignasis. This gynecological malignancy is very common all over the world, especially in developed countries and shows a potentially rising trend correlated with the increase in obese women. Methods: Differentially Expressed Genes (DEGs) analysis was conducted on GSE7305 and GSE25628 datasets from the Gene Expression Omnibus (GEO). DEGs were identified using GEO2R (adjusted p-value 1). Pathway analysis employed KEGG and Gene Ontology databases, while protein-protein interactions were analyzed using Cytoscape and Gephi. GEPIA was used for target gene validation. Results: We have identified 304 common DEGs and 78 hub genes using GEO and PPI analysis, respectively. The GO and KEGG pathways analysis revealed enrichment of DEGs in extracellular matrix structural constituent, extracellular space, cell adhesion, and ECM-receptor interaction. GEPIA analysis identified three genes, ENG, GNG4, and ECT2, whose expression significantly differed between normal and tumor samples. Conclusion: This analysis study identified the hub genes and associated pathways involved in the pathogenesis of UCEC. The identified hub genes exhibit remarkable potential as diagnostic biomarkers, providing a significant opportunity for early diagnosis and more effective therapeutic approaches for UCE
Relationship of the Prime Diet Quality Score (PDQS) and Healthy Eating Index (HEI-2015) with depression and anxiety: a cross-sectional study
No full textBackground: Previous studies have suggested a significant association between diet quality and mental health. However, a limited number of studies have utilized the Prime Diet Quality Score (PDQS) to examine this association. Additionally, no study has yet compared the PDQS and Healthy Eating Index-2015 (HEI-2015) in terms of their association with depression and anxiety. Aim: This cross-sectional study aimed to investigate the association between diet quality, measured by the PDQS and HEI-2015, and the odds of depression and anxiety in adults. Methods: This study utilized data from the LIPOKAP study, which was conducted between February 2018 and July 2019 in five cities in Iran. We included 1994 adults aged 18 and above who were selected through a multistage cluster sampling method. Participants completed a validated semiquantitative food frequency questionnaire (FFQ) to evaluate their dietary intake. The FFQ was used to calculate the PDQS and HEI-2015. Depression and anxiety levels were determined using the Hospital Anxiety and Depression Scale (HADS). Results: The participants had a mean age of 39.79 ± 13.87 years, with females accounting for 1,041 (52.2%) of the total population. PDQS showed a significant inverse association with the odds of depression (OR = 0.45, 95% CI: 0.28–0.71) and anxiety (OR = 0.40, 95% CI: 0.25–0.62) in the fully adjusted model. Similarly, the highest quartile of HEI-2015 showed a significantly lower odds of depression (OR = 0.60, 95% CI: 0.40–0.90) and anxiety (OR = 0.62, 95% CI: 0.42–0.92) compared to the lowest quartile. Conclusion: Both PDQS and HEI-2015 were associated with a reduced risk of depression and anxiety. However, the PDQS demonstrated a stronger inverse association with these risks compared to the HEI-2015. This suggests that the PDQS could be a more beneficial dietary pattern for preventing depression and anxiety compared to HEI-2015. Further large-scale studies are required to confirm these findings
Clinical and preclinical advances in PSMA-Directed Antibody-Drug conjugates (ADCs): Current status and hope for the future
No full textProstate-specific membrane antigen (PSMA) is a type II membrane glycoprotein overexpressed in a variety of tumors, especially in nearly all prostate cancers, which makes it a potentially attractive antigen for targeted cancer therapies. More importantly, PSMA, due to no shedding into circulation and efficient internalization after antibody binding, becomes a potential target for antibody-drug conjugates (ADCs), a valid and emerging paradigm of cancer treatment. Four and eight PSMA-directed ADCs have been or are currently being investigated in clinical trials (three of which failed to confirm the promising results while one is currently being evaluated in an ongoing clinical study) and preclinical studies, respectively, for the treatment of PSMA-positive solid tumors, especially prostate cancer. The present study aims to completely review clinical- and preclinical-stage PSMA-directed ADCs
Innovative genetic scissor strategies and their applications in cancer treatment and prevention: CRISPR modules and challenges
No full textThere are lots of gene editing tools for targeting genome sequences. Some are almost known, and most are a complete mystery and undiscovered. CRISPR/Cas editing tools have brought about a major revolution in medicine. Researchers have shown that CRISPR can modify DNA much more accurately, economically and easily than previous methods. CRISPR has proven itself effective for the deletion, replacement and insertion of DNA fragments into cell types, tissues and organisms. Recently, combining CRISPR/Cas with factors (transcription factors/repressors, exonucleases, endonucleases, transposons, caspase, fluorescent proteins, oxidoreductive enzymes, DNA/RNA polymerases), and elements (aptamers, barcodes, fluorescent probes, Trigger) have provided genome, transcriptome, proteome and epigenome modification. These modules are being investigated for cancer prevention and therapy and this review focuses on such innovative combinations that hopefully will become a clinical reality in the near future
Synthesis and characterization of CuCoFe2O4@GA/AC as a bio-based matrix magnetic nano-heterogeneous photocatalyst for ceftriaxone degradation from aqueous media
No full textEmerging contaminants such as ceftriaxone are a significant issue in the environment. They have led to a series of ecological, environmental, and health issues, and it is urgent to find a green and secure method to remove antibiotics from water effectively. In this research, the CuCoFe2O4@Gum Arabic (GA)/Activated Carbon (AC) as an innovative bio-based matrix magnetic nanocatalyst was synthesized for the efficient degradation of ceftriaxone from aqueous media. The structure of CuCoFe2O4@GA/AC was characterized via FESEM, EDS, Mapping, XRD, FTIR, VSM, and DRS analyses. The structural analysis of the catalyst revealed its synthesis at the nanometer scale (40–50 nm), exhibiting high magnetic strength (Ms: 5.38 emu/g) and favorable optical properties with a bandgap of 3.6 eV. Under optimized conditions, including a pH of 5, 60 min of irradiation time, 0.24 g/L photocatalyst dose, and ceftriaxone concentration of 5 mg/L, the removal efficiency from synthetic and real samples was 94.43% and 62.5%, respectively. The photocatalytic degradation process of ceftriaxone followed pseudo-first-order and Langmuir–Hinshelwood kinetic models. Furthermore, analysis of the process mechanism indicated a prominent role of the superoxide radical. The catalyst had a high recovery capability and chemical stability. The photocatalytic degradation of ceftriaxone by CuCoFe2O4@GA/AC showcased remarkable efficiency, indicating its potential utility in the treatment of wastewater contaminated with antibiotics
Bactericidal Activity of Serum by Brucella Abortus RB51 Outer Membrane Protein’s Combined by Brucella Abortus S99 Lipopolysaccharide Induction
No full textBackground: Brucellosis vaccines are designed to induce cellular immunity. An effective brucellosis vaccine could induce both cellular and humoral immunity. Serum Bactericidal Assay (SBA) is an important method for determining vaccine humoral immunity. This study is the first to observe humoral immunity in brucellosis by SBA. Methods: Extracted Brucella abortus (B. abortus) Lipopolysaccharide (LPS) and Outer Membrane Proteins (OMPs) were injected into rabbits. Group 1 was injected with 25 µg of LPS, Group 2 was injected with 50 µg of OMPs, and Group 3 was injected with 1 ml of combined vaccine, 3 times every 2 weeks. The groups were challenged with B. abortus 544 in the second injection. Sera were separated 2 weeks after the last injection. SBA was performed, and each well was streak-cultured into a plate of Brucella agar. A colony count was done for each plate. Results: Results have shown, the third injection of the combined vaccine had the highest titer of1 64, and the efficacy of the vaccine was 87.71%. Conclusion: As a conclusion, the results of this study showed that LPS and OMP's from B. abortus can provide acceptable immunity
Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021
No full textBackground: Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. Methods: We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined. Findings: Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer. Interpretation: As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed. Funding: Bill & Melinda Gates Foundation
Epigenetic Disruption of Histone Deacetylase-2 Accelerated Apoptotic Signaling and Retarded Malignancy in Gastric Cells
No full textBackground: The objective of this research was to determine whether HDAC2 function is associated with gastric cancer progression. Methods: HDAC2 was knocked out in EPG85.257 cells using CRISPR/Cas9 and tumorigenesis pathways were evaluated. Results: Cell proliferation, colony formation, wound healing and transwell invasion were inhibited in ▵HDAC2:EPG85.257 cells. Quantitative analyses revealed a significant downregulation of MMP1, p53, Bax, MAPK1, MAPK3, pro-Caspase3, ERK1/2, p-ERK1/2, AKT1/2/3, p-AKT1/2/3, p-NF-κB (p65), Twist, Snail and p-FAK transcripts/proteins, while SIRT1, PTEN, p21 and Caspase3 were upregulated in ▵HDAC2:EPG85.257 cells. Conclusion: These results indicated that HDAC2 enhanced migration, colony formation and transmigration ability. HDAC2 inhibition may improve gastric cancer chemotherapy pathway
Investigation of bioremediation for glyphosate and its metabolite in soil using arbuscular mycorrhizal GmHsp60 protein: a molecular docking and molecular dynamics simulations approach
No full textThe widespread use of glyphosate and the high dependence of the agricultural industry on this herbicide cause environmental pollution and pose a threat to living organisms. One of the appropriate solutions in sustainable agriculture to deal with pollution caused by glyphosate and its metabolites is creating a symbiotic relationship between plants and mycorrhizal fungi. Glomalin-related soil protein is a key protein for the bioremediation of glyphosate and its metabolite aminomethyl phosphonic acid in soil. This study uses homology modeling, molecular docking, and molecular dynamic simulation approaches to investigate the binding mechanism of glomalin-related soil protein from arbuscular mycorrhiza (GmHsp60) with glyphosate and its metabolite and the role of soil protein in the removal and sequestering of common agricultural soil pollutants. GmHsp60 protein structure was predicted by homology modeling, and the quality of the generated model was assessed. Then, the interaction between glyphosate and aminomethyl phosphonic acid and the modeled GmHsp60 protein was explored by molecular docking. Based on docking results, GmHsp60 has an efficient role in the bioremediation of glyphosate and aminomethyl phosphonic acid (-6.03 and −5.34 kcal/mol). Glyphosate forms three hydrogen bonds with Lys258, Gly262, and Glu58 of GmHsp60, and aminomethyl phosphonic acid forms three hydrogen bonds with Lys258, Gly261, and Gly262 of GmHsp60. In addition, the glyphosate’s and its metabolite’s stability was confirmed by molecular docking simulations and binding free energy calculations using MM/PBSA analysis. This study provides a molecular-level understanding of GmHsp60 expression and function for glyphosate bioremediation