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Iranian Journal of Immunology : IJI May 2024The mechanisms of the function of interferon beta (IFN-β) and natalizumab (NTZ) in multiple sclerosis (MS) patients have not yet been fully understood. Over the past...
The Effect of Interferon Beta and Natalizumab on miR-20b Expression in Patients with Relapsing-Remitting Multiple Sclerosis is Potentially Mediated by Modulation of the Jak-STAT Signaling Pathway: A Case-control Study.
BACKGROUND
The mechanisms of the function of interferon beta (IFN-β) and natalizumab (NTZ) in multiple sclerosis (MS) patients have not yet been fully understood. Over the past decades, many studies have been conducted to evaluate gene expression changes especially regulatory non-coding RNAs such as microRNAs (miRNAs) following therapy in MS patients.
OBJECTIVE
To assess the changes in the expression of miR-20b in MS patients treated with IFN-β or NTZ.
METHODS
Sixty patients with relapsing-remitting MS (RRMS) and 30 healthy controls (HCs) were enrolled. The patients were categorized as untreated (N=20), IFN-β-treated (N=20), and NTZtreated (N=20). For the expression analysis, real-time PCR was performed on the whole blood. The bioinformatic tools were applied for signaling pathways enrichment analysis of miR-20b targetome.
RESULTS
The relative expression of miR-20b was significantly downregulated in the untreated patients compared with the HCs (-1.726-fold, p<0.001), while IFN-β-treated and NTZ-treated patients showed no statistical difference compared with the HCs (0.733-fold, p=0.99 for IFN-β and 1.025-fold, p=0.18 for NTZ). This indicates the restoration of miR-20b expression to normal level in the treated patients. Additionally, in silico analysis demonstrated that the Jak-STAT signaling pathway is enriched with miR-20b targets (p<0.0001).
CONCLUSION
Our findings suggest that the positive effects of IFN-β and NTZ in the RRMS patients could be potentially mediated by returning miR-20b expression to baseline.
PubMed: 38761094
DOI: 10.22034/iji.2024.100500.2694 -
Life Science Alliance Aug 2024Dynamic rearrangements of the F-actin cytoskeleton are a hallmark of tumor metastasis. Thus, proteins that govern F-actin rearrangements are of major interest for...
Dynamic rearrangements of the F-actin cytoskeleton are a hallmark of tumor metastasis. Thus, proteins that govern F-actin rearrangements are of major interest for understanding metastasis and potential therapies. We hypothesized that the unique F-actin binding and bundling protein SWAP-70 contributes importantly to metastasis. Orthotopic, ectopic, and short-term tail vein injection mouse breast and lung cancer models revealed a strong positive dependence of lung and bone metastasis on SWAP-70. Breast cancer cell growth, migration, adhesion, and invasion assays revealed SWAP-70's key role in these metastasis-related cell features and the requirement for SWAP-70 to bind F-actin. Biophysical experiments showed that tumor cell stiffness and deformability are negatively modulated by SWAP-70. Together, we present a hitherto undescribed, unique F-actin modulator as an important contributor to tumor metastasis.
Topics: Animals; Actins; Mice; Humans; Female; Cell Line, Tumor; Neoplasm Metastasis; Breast Neoplasms; Lung Neoplasms; Microfilament Proteins; Cell Movement; Actin Cytoskeleton; Cell Proliferation; Cell Adhesion; Protein Binding
PubMed: 38760173
DOI: 10.26508/lsa.202302307 -
International Journal of... 2024This study aimed to explore the potential correlation between specific single nucleotide polymorphisms (TYK2, IFITM3, IFNAR2, and OAS3 variants) and the severity of...
OBJECTIVES
This study aimed to explore the potential correlation between specific single nucleotide polymorphisms (TYK2, IFITM3, IFNAR2, and OAS3 variants) and the severity of COVID-19 in Moroccan patients.
METHODS
A genetic analysis was conducted on 109 patients with PCR-confirmed SARS-CoV-2 infection in Morocco. Among these patients, 46% were hospitalized in the intensive care unit, while 59% were not hospitalized. Importantly, all patients lacked known risk factors associated with COVID-19 severity. Genotyping was performed to identify variations in TYK2 rs74956615, IFITM3 rs12252, IFNAR2 rs2236757, and OAS3 rs10735079. Statistical analysis was applied using codominant, dominant and recessive logistic regression models to assess correlations with COVID-19 severity.
RESULTS
Our findings revealed no significant correlation between TYK2 rs74956615, IFITM3 rs12252, IFNAR2 rs2236757, and OAS3 rs10735079 with COVID-19 severity in Moroccan patients, as indicated in logistic regression models ( > .05). Interestingly, these results may offer insights into the mitigated impact of the COVID-19 pandemic and the reduced severity observed in SARS-CoV-2 infected patients in Morocco. Age, however, exhibited a significant correlation with severity ( < .001), with a trend towards increased likelihood of ICU admission with advancing age. Additionally, In the severe group, a higher proportion of patients were females (54%), indicating a statistically significant correlation with disease severity ( = .04). Nevertheless, female ICU patients aged above 60 years accounted for 37%, compared to 17% for males.
CONCLUSION
This study underscores the absence of a genetic association between the selected polymorphisms and COVID-19 severity in Moroccan patients. Advanced age emerges as the primary factor influencing the severity of COVID-19 patients without comorbidities. We recommend setting the threshold for advanced age at 60 years as a risk factor for severe forms of COVID-19.
Topics: Humans; Female; Male; COVID-19; Morocco; Middle Aged; Polymorphism, Single Nucleotide; Membrane Proteins; Adult; Intensive Care Units; Severity of Illness Index; RNA-Binding Proteins; TYK2 Kinase; Receptor, Interferon alpha-beta; Aged; 2',5'-Oligoadenylate Synthetase; SARS-CoV-2; Genetic Predisposition to Disease
PubMed: 38760017
DOI: 10.1177/03946320241257241 -
Revista Portuguesa de Cardiologia :... May 2024
PubMed: 38759915
DOI: 10.1016/j.repc.2024.05.004 -
Cell Reports Methods May 2024Organoids, self-organizing three-dimensional (3D) structures derived from stem cells, offer unique advantages for studying organ development, modeling diseases, and... (Review)
Review
Organoids, self-organizing three-dimensional (3D) structures derived from stem cells, offer unique advantages for studying organ development, modeling diseases, and screening potential therapeutics. However, their translational potential and ability to mimic complex in vivo functions are often hindered by the lack of an integrated vascular network. To address this critical limitation, bioengineering strategies are rapidly advancing to enable efficient vascularization of organoids. These methods encompass co-culturing organoids with various vascular cell types, co-culturing lineage-specific organoids with vascular organoids, co-differentiating stem cells into organ-specific and vascular lineages, using organoid-on-a-chip technology to integrate perfusable vasculature within organoids, and using 3D bioprinting to also create perfusable organoids. This review explores the field of organoid vascularization, examining the biological principles that inform bioengineering approaches. Additionally, this review envisions how the converging disciplines of stem cell biology, biomaterials, and advanced fabrication technologies will propel the creation of increasingly sophisticated organoid models, ultimately accelerating biomedical discoveries and innovations.
PubMed: 38759654
DOI: 10.1016/j.crmeth.2024.100779 -
Poultry Science Apr 2024Previously, we reported that glucagon-like peptide-1 (GLP-1) and its analog liraglutide could inhibit fat de novo synthesis in the liver and reduce abdominal fat...
Previously, we reported that glucagon-like peptide-1 (GLP-1) and its analog liraglutide could inhibit fat de novo synthesis in the liver and reduce abdominal fat accumulation in broiler chickens. Nevertheless, the impact of GLP-1 on adipocyte fat deposition remains enigmatic. This study aimed to investigate the effects of GLP-1, via its analog liraglutide, on chicken chicken adipocytes in vitro. Chemical assays, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot were employed to assess the proliferation, differentiation, and fat deposition of chicken adipocytes. Our findings indicated that liraglutide significantly suppressed cell proliferation and promoted preadipocyte differentiation in comparison to the control group. This was evidenced by elevated triglyceride (TG) content and upregulated mRNA expression of lipogenesis-related enzymes, such as acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), as well as regulators including peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element binding protein-1 (SREBP1) and CCAAT/enhancer binding protein α (CEBPα). In mature adipocytes, liraglutide attenuated fat deposition by inhibiting fat de novo synthesis, evidenced by decreased mRNA expression of ACC, FAS, PPARγ, C/EBPα, and SREBP1, and concurrent upregulation of phosphorylated AMP-activated protein kinase (p-AMPK) and phosphorylated ACC (p-ACC). This resulted in reduced accumulation of lipid droplets and TG content in mature adipocytes. Collectively, our findings indicate that liraglutide suppresses the proliferation of preadipocytes, enhances their differentiation, and concurrently inhibits de novo lipogenesis in mature adipocytes. This observation offers profound insights into the mechanisms that underlie liraglutide's anti-adipogenic effects, which could have significant implications for the treatment of obesity in broiler chickens.
PubMed: 38759567
DOI: 10.1016/j.psj.2024.103766 -
PloS One 2024Plant growth-promoting rhizobacteria (PGPR) applications have emerged as an ideal substitute for synthetic chemicals by their ability to improve plant nutrition and...
Plant growth-promoting rhizobacteria (PGPR) applications have emerged as an ideal substitute for synthetic chemicals by their ability to improve plant nutrition and resistance against pathogens. In this study, we isolated fourteen root endophytes from healthy wheat roots cultivated in Tunisia. The isolates were identified based from their 16S rRNA gene sequences. They belonged to Bacillota and Pseudomonadota taxa. Fourteen strains were tested for their growth-promoting and defense-eliciting potentials on durum wheat under greenhouse conditions, and for their in vitro biocontrol power against Fusarium culmorum, an ascomycete responsible for seedling blight, foot and root rot, and head blight diseases of wheat. We found that all the strains improved shoot and/or root biomass accumulation, with Bacillus mojavensis, Paenibacillus peoriae and Variovorax paradoxus showing the strongest promoting effects. These physiological effects were correlated with the plant growth-promoting traits of the bacterial endophytes, which produced indole-related compounds, ammonia, and hydrogen cyanide (HCN), and solubilized phosphate and zinc. Likewise, plant defense accumulations were modulated lastingly and systematically in roots and leaves by all the strains. Testing in vitro antagonism against F. culmorum revealed an inhibition activity exceeding 40% for five strains: Bacillus cereus, Paenibacillus peoriae, Paenibacillus polymyxa, Pantoae agglomerans, and Pseudomonas aeruginosa. These strains exhibited significant inhibitory effects on F. culmorum mycelia growth, sporulation, and/or macroconidia germination. P. peoriae performed best, with total inhibition of sporulation and macroconidia germination. These finding highlight the effectiveness of root bacterial endophytes in promoting plant growth and resistance, and in controlling phytopathogens such as F. culmorum. This is the first report identifying 14 bacterial candidates as potential agents for the control of F. culmorum, of which Paenibacillus peoriae and/or its intracellular metabolites have potential for development as biopesticides.
Topics: Fusarium; Triticum; Endophytes; Biological Control Agents; Plant Diseases; Plant Roots; Tunisia; Bacteria; RNA, Ribosomal, 16S
PubMed: 38758965
DOI: 10.1371/journal.pone.0300791 -
PloS One 2024The primary objective of this study was to isolate bacteria from diabetic foot ulcers and subsequently assess their antibiotic resistance capabilities. Seventy-five...
The primary objective of this study was to isolate bacteria from diabetic foot ulcers and subsequently assess their antibiotic resistance capabilities. Seventy-five patients diagnosed with diabetic foot ulcers were investigated. A number of these patients (97.33%) had type 2 diabetes, with a significant proportion of them having been diagnosed for 1-5 years (29.33%). Notably, a substantial number of these individuals were on insulin usage (78.66%). Among the patients under examination, 49.33% reported having no use of tobacco products, alcohol, or betel leaf. The ulcers analyzed in this study were classified into grades 1-5 according to the Wagner scale. Wagner grade 2 diabetic foot ulcers had the highest number of culture-positive patients, at 33.33%. Pus samples collected from patients were cultured on selective media, and bacterial identity was confirmed by biochemical tests and polymerase chain reaction. A total of 141 isolates were isolated. Among the isolates, 82.97% gram-negative bacteria and 17.02% gram-positive bacteria were detected. Klebsiella pneumoniae was the most common isolate. Proteus spp., Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were also detected. Approximately 61.33% of the ulcers exhibited were polybacterial. In this study, it was observed that all bacterial isolates, except for Proteus spp., were primarily detected in patients classified under Wagner's grade 2. Moreover, antibiotic susceptibility was also tested on these 141 isolates. Among them, Escherichia coli showed the highest multidrug resistance, 81.81%. Most of the gram-negative bacteria were resistant to ampicillin. All of the gram-negative isolates exhibited high levels of susceptibility to piperacillin-tazobactam, and these levels were Klebsiella pneumoniae (97.56%), Pseudomonas aeruginosa (95.24%), Escherichia coli (81.82%), and Proteus spp. (80%). On the other hand, gram-positive Staphylococcus aureus mostly showed sensitivity towards vancomycin and norfloxacin (79.17%).
Topics: Humans; Diabetic Foot; Male; Female; Middle Aged; Anti-Bacterial Agents; Microbial Sensitivity Tests; Bangladesh; Aged; Adult; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Escherichia coli; Diabetes Mellitus, Type 2; Staphylococcus aureus
PubMed: 38758936
DOI: 10.1371/journal.pone.0301767 -
PloS One 2024Mpox (formerly known as monkeypox) virus and some related poxviruses including smallpox virus pose a significant threat to public health, and effective prevention and...
Mpox (formerly known as monkeypox) virus and some related poxviruses including smallpox virus pose a significant threat to public health, and effective prevention and treatment strategies are needed. This study utilized a reverse vaccinology approach to retrieve conserved epitopes for monkeypox virus and construct a vaccine that could provide cross-protection against related viruses with similar antigenic properties. The selected virulent proteins of monkeypox virus, MPXVgp165, and Virion core protein P4a, were subjected to epitope mapping for vaccine construction. Two vaccines were constructed using selected T cell epitopes and B cell epitopes with PADRE and human beta-defensins adjuvants conjugated in the vaccine sequence. Both constructs were found to be highly antigenic, non-allergenic, nontoxic, and soluble, suggesting their potential to generate an adequate immune response and be safe for humans. Vaccine construct 1 was selected for molecular dynamic simulation studies. The simulation studies revealed that the TLR8-vaccine complex was more stable than the TLR3-vaccine complex. The lower RMSD and RMSF values of the TLR8 bound vaccine compared to the TLR3 bound vaccine suggested better stability and consistency of hydrogen bonds. The Rg values of the vaccine chain bound to TLR8 indicated overall stability, whereas the vaccine chain bound to TLR3 showed deviations throughout the simulation. These results suggest that the constructed vaccine could be a potential preventive measure against monkeypox and related viruses however, further experimental validation is required to confirm these findings.
Topics: Humans; Monkeypox virus; Molecular Dynamics Simulation; Epitopes, T-Lymphocyte; Epitopes, B-Lymphocyte; Computer Simulation; Poxviridae; Viral Vaccines; Epitope Mapping; Mpox (monkeypox); Animals; Toll-Like Receptor 8
PubMed: 38758816
DOI: 10.1371/journal.pone.0300778 -
PloS One 2024Malathion® is a persistent organophosphate pesticide used against biting and chewing insects on vegetables. It is a difficult-to-remove surface contaminant of...
Malathion® is a persistent organophosphate pesticide used against biting and chewing insects on vegetables. It is a difficult-to-remove surface contaminant of vegetables and contaminates surface and ground water and soils. Malathion® is only partially water soluble, but use of detergent carriers makes adhering Malathion® residues difficult to subsequently remove. Magnetically treated water (MTW) successfully removed Malathion® from Chinese Kale (Brassica oleracea L.), meeting Maximum Residue Load (MRL) standards. Samples were soaked in MTW for 30 min prior to detection with GC/MS/MS, 98.5±3.02% of Malathion® was removed after washing by MTW. Removal by simple washing was only ≈42±1.2% which was not nearly sufficient to meet MRL criteria.
Topics: Brassica; Malathion; Water Pollutants, Chemical; Water; Insecticides; Pesticide Residues; Water Purification; Food Contamination; Gas Chromatography-Mass Spectrometry
PubMed: 38758738
DOI: 10.1371/journal.pone.0298371