Partition coefficient screening - An effective approach for finding the best conditions for byproduct removal as demonstrated by a bispecific antibody purification case.

In recombinant protein purification, differences in isoelectric point (pI)/surface charge and hydrophobicity between the product and byproducts generally form the basis for separation. For bispecific antibodies (bsAbs), in many cases the physicochemical difference between product and byproducts is subtle, making byproduct removal considerably challenging. In a previous report, with a bsAb case study, we showed that partition coefficient (Kp) screening for the product and byproducts under various conditions facilitated finding conditions under which effective separation of two difficult-to-remove byproducts was achieved by anion exchange (AEX) chromatography. In the current work, as a follow-up study, we demonstrated that the same approach enabled identification of conditions allowing equally good byproduct removal by mixed-mode chromatography with remarkably improved yield. Results from the current and previous studies proved that separation factor determination based on Kp screening for product and byproduct is an effective approach for finding conditions enabling efficient and maximum byproduct removal, especially in challenging cases.

Comprehensive metabolic profiling of dioxin-like compounds exposure in laying hens: Implications for toxicity assessment.

The evaluation of toxicity related to polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) is crucial for a comprehensive risk assessment in real-world exposure scenarios. This study employed a controlled feeding experiment to investigate the metabolic effects of dioxin-like compounds (DLCs) on laying hens via feed exposure. Diets enriched with two concentrations (1.17 and 5.13 pg toxic equivalents (TEQ)/g dry weight (dw)) were administered over 14 days, followed by 28 days of clean feed. Metabolomics analyses of blood samples revealed significant metabolic variations between PCDD/Fs and DL-PCBs exposed groups and controls, reflecting the induced metabolic disruption. Distinct changes were observed in sphingosine, palmitoleic acid, linoleate, linolenic acid, taurocholic acid, indole acrylic acid, and dibutyl phthalate levels, implying possible connections between PCDD/Fs and DL-PCBs toxic effects and energy-neuronal imbalances, along with lipid accumulation and anomalous amino acid metabolism, impacting taurine metabolism. Moreover, we identified three differential endogenous metabolites-L-tryptophan, indole-3-acetaldehyde, and indole acrylic acid-as potential ligands for the aryl hydrocarbon receptor (AhR), suggesting their role in mediating PCDD/Fs and DL-PCBs toxicity. This comprehensive investigation provides novel insights into the metabolic alterations induced by PCDD/Fs and DL-PCBs in laying hens, thereby enhancing our ability to assess risks associated with their exposure in human populations.

A highly sensitive electrochemical sensor based on poly(3-aminobenzoic acid)/graphene oxide-gold nanoparticles modified screen printed carbon electrode for paraquat detection.

Herein, a modified screen printed carbon electrode (SPCE) based on a composite material, graphene oxide-gold nanoparticles (GO-AuNPs), and poly(3-aminobenzoic acid)(P3ABA) for the detection of paraquat (PQ) is introduced. The modified electrode was fabricated by drop casting of the GO-AuNPs, followed by electropolymerization of 3-aminobenzoic acid to achieve SPCE/GO-AuNPs/P3ABA. The morphology and microstructural characteristics of the modified electrodes were revealed by scanning electron microscopy (SEM) for each step of modification. The composite GO-AuNPs can provide high surface area and enhance electroconductivity of the electrode. In addition, the presence of negatively charged P3ABA notably improved PQ adsorption and electron transfer rate, which stimulate redox reaction on the modified electrode, thus improving the sensitivity of PQ analysis. The SPCE/GO-AuNPs/P3ABA offered a wide linear range of PQ determination (10-9-10-4 mol/L) and low limit of detection (LOD) of 0.45 × 10-9 mol/L or 0.116 µg/L, which is far below international safety regulations. The modified electrode showed minimum interference effect with percent recovery ranging from 96.5% to 116.1% after addition of other herbicides, pesticides, metal ions, and additives. The stability of the SPCE/GO-AuNPs/P3ABA was evaluated, and the results indicated negligible changes in the detection signal over 9 weeks. Moreover, this modified electrode was successfully implemented for PQ analysis in both natural and tapped water with high accuracy.

Sea buckthorn extract mitigates chronic obstructive pulmonary disease by suppression of ferroptosis via scavenging ROS and blocking p53/MAPK pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Sea buckthorn (Hippophae rhamnoides), a traditional Tibetan medicinal herb, exhibits protective effects against cardiovascular and respiratory diseases. Although Sea buckthorn extract (SBE) has been confirmed to alleviate airway inflammation in mice, its therapeutic effect and underlying mechanism on chronic obstructive pulmonary disease (COPD) requires further clarification. AIM OF THE STUDY: To elucidate the alleviative effect and molecular mechanism of SBE on lipopolysaccharides (LPS)/porcine pancreatic elastase (PPE)-induced COPD by blocking ferroptosis. METHODS: The anti-ferroptotic effects of SBE were evaluated in human BEAS-2B bronchial epithelial cells using CCK8, RT-qPCR, western blotting, and transmission electron microscopy. Transwell was employed to detect chemotaxis of neutrophils. COPD model was induced by intranasally administration of LPS/PPE in mice and measured by alterations of histopathology, inflammation, and ferroptosis. RNA-sequencing, western blotting, antioxidant examination, flow cytometry, DARTS, CETSA, and molecular docking were then used to investigate its anti-ferroptotic mechanisms. RESULTS: In vitro, SBE not only suppressed erastin- or RSL3-induced ferroptosis by suppressing lipid peroxides (LPOs) production and glutathione (GSH) depletion, but also suppressed ferroptosis-induced chemotactic migration of neutrophils via reducing mRNA expression of chemokines. In vivo, SBE ameliorated LPS/PPE-induced COPD phenotypes, and inhibited the generation of LPOs, cytokines, and chemokines. RNA-sequencing showed that p53 pathway and mitogen-activated protein kinases (MAPK) pathway were implicated in SBE-mediated anti-ferroptotic action. SBE repressed erastin- or LPS/PPE-induced overactivation of p53 and MAPK pathway, thereby decreasing expression of diamine acetyltransferase 1 (SAT1) and arachidonate 15-lipoxygenase (ALOX15), and increasing expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11). Mechanistically, erastin-induced elevation of reactive oxygen species (ROS) was reduced by SBE through directly scavenging free radicals, thereby contributing to its inhibition of p53 and MAPK pathways. CETSA, DARTS, and molecular docking further showed that ROS-generating enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) may be the target of SBE. Overexpression of NOX4 partially impaired the anti-ferroptotic activity of SBE. CONCLUSION: Our results demonstrated that SBE mitigated COPD by suppressing p53 and MAPK pro-ferroptosis pathways via directly scavenging ROS and blocking NOX4. These findings also supported the clinical application of Sea buckthorn in COPD therapy.

Investigating the synergistic antibacterial effects of chlorogenic and p-coumaric acids on Shigella dysenteriae.

Chlorogenic acid (CGA) is a well-known plant secondary metabolite exhibiting multiple physiological functions. The present study focused on screening for synergistic antibacterial combinations containing CGA. The combination of CGA and p-coumaric acid (pCA) exhibited remarkably enhanced antibacterial activity compared to that when administering the treatment only. Scanning electron microscopy revealed that a low-dose combination treatment could disrupt the Shigella dysenteriae cell membrane. A comprehensive analysis using nucleic acid and protein leakage assay, conductivity measurements, and biofilm formation inhibition experiments revealed that co-treatment increased the cell permeability and inhibited the biofilm formation substantially. Further, the polyacrylamide protein- and agarose gel-electrophoresis indicated that the proteins and DNA genome of Shigella dysenteriae severely degraded. Finally, the synergistic bactericidal effect was established for fresh-cut tomato preservation. This study demonstrates the remarkable potential of strategically selecting antibacterial agents with maximum synergistic effect and minimum dosage exhibiting excellent antibacterial activity in food preservation.

ADAR1-regulated miR-142-3p/RIG-I axis suppresses antitumor immunity in nasopharyngeal carcinoma.

Following the initial treatment of nasopharyngeal carcinoma (NPC), tumor progression often portends an adverse prognosis for these patients. MicroRNAs (miRNAs) have emerged as critical regulators of tumor immunity, yet their intricate mechanisms in NPC remain elusive. Through comprehensive miRNA sequencing, tumor tissue microarrays and tissue samples analysis, we identified miR-142-3p as a significantly upregulated miRNA that is strongly associated with poor prognosis in recurrent NPC patients. To elucidate the underlying molecular mechanism, we employed RNA sequencing, coupled with cellular and tissue assays, to identify the downstream targets and associated signaling pathways of miR-142-3p. Our findings revealed two potential targets, CFL2 and WASL, which are directly targeted by miR-142-3p. Functionally, overexpressing CFL2 or WASL significantly reversed the malignant phenotypes induced by miR-142-3p both in vitro and in vivo. Furthermore, signaling pathway analysis revealed that miR-142-3p repressed the RIG-I-mediated immune defense response in NPC by inhibiting the nuclear translocation of IRF3, IRF7 and p65. Moreover, we discovered that ADAR1 physically interacted with Dicer and promoted the formation of mature miR-142-3p in a dose-dependent manner. Collectively, ADAR1-mediated miR-142-3p processing promotes tumor progression and suppresses antitumor immunity, indicating that miR-142-3p may serve as a promising prognostic biomarker and therapeutic target for NPC patients.

Improved production of class I phosphatidylinositol 4,5-bisphosphate 3-kinase.

Phosphatidylinositol 4,5-bisphosphate 3-kinases (PI3K) are a family of kinases whose activity affects pathways needed for basic cell functions. As a result, PI3K is one of the most mutated genes in all human cancers and serves as an ideal therapeutic target for cancer treatment. Expanding on work done by other groups we improved protein yield to produce stable and pure protein using a variety of modifications including improved solubility tag, novel expression modalities, and optimized purification protocol and buffer. By these means, we achieved a 40-fold increase in yield for p110α/p85α and a 3-fold increase in p110α. We also used these protocols to produce comparable constructs of the ß and δ isoforms of PI3K. Increased yield enhanced the efficiency of our downstream high throughput drug discovery efforts on the PIK3 family of kinases.

MiR-204-5p overexpression abrogates Dacarbazine-induced senescence in melanoma cells in vivo MiR-204-5p abrogates senescence.

Cancer cell drug resistance hinders significantly therapeutic modalities in oncology. Dacarbazine is chemotherapeutic agent traditionally used for melanoma treatment although it's effectiveness insufficient. In the present study we performed NGS-based transcriptomic profiling of B16 melanoma tumors after Dacarbazine treatment in vivo. Whole transcriptome sequencing revealed 34 differentially expressed genes most of them associated with drug resistance and apoptosis evading. In accordance to bionformatic analysis, 6 signaling cascades: "D-Amino acid metabolism", "NF-kappa B signaling pathway", "Phosphatidylinositol signaling system", "P53 signaling pathway", "IL-17 signaling pathway" and "Bile secretion" were enriched by differentially expressed genes. Next we provided a combined treatment by Dacarbazine and miR-204-5p mimic as miR-204-5p was considered previously implicated in cancer drug resistance. This approach lead to an increase of miR-204-5p expression in B16 melanoma cells in vivo that was accompanied by subsequent decrease in the expression of miR-204-5p target genes - BCL2 and SIRT1 in the primary tumors. MiR-204-5p overexpression with Dacarbazine application resulted in increased the weight, and volume of primary tumors and diminished the proportion of ß-Galactosidase expression in melanoma B16-bearing mice. Taking together, our study revealed that although miR-204-5p showed antiproliferative capacities in vitro, it's mimic in combination with Dacarbazine is able to potentiate tumor growth triggering probably a switch from senescent to proliferative phenotype of malignant cells.

In-situ synthesis of heteroatom-doped hard carbon for sodium-ion batteries: Dual benefits for green energy and environment.

Heteroatom-doped carbon has been widely investigated as anode materials for sodium-ion batteries (SIBs). However, simplifying the preparation process and precisely controlling their microstructure to achieve excellent Na+ storage performance remain significant challenges. Therefore, in this study, high-performance N, P co-doped Na+ storage carbon anode electrode materials were prepared by one-step carbonization using N, P-rich Eichhornia crassipes (EC) as raw materials and systematically tested for their Na+ storage performance. The doping levels of N and P atoms as well as the spatial structure of the carbon material were adjusted by changing the carbonization temperature during the pyrolysis process. Among them, the anode material corresponding to 1300 °C (EC-PN1300) showed an excellent Na+ storage capacity of 336 ± 4 mAh g-1 (50 mA g-1) and excellent cycling stability (99.8 % retention after 2000 cycles). In addition, the Na+ storage mechanism of EC-PN1300 was systematically analyzed using galvanostatic intermittent titration (GITT), ex-situ XPS and in-situ Raman spectroscopy, providing accurate research directions for developing carbon anode electrode materials with superior electrochemical performance. This study not only provides some insights into the preparation of carbon anode materials in alkali metal batteries and the development of carbon materials in other fields, but also realizes the interaction between environmental protection and new energy development.

Highly active nitrogen-phosphorus co-doped carbon fiber@graphite felt electrode for high-performance vanadium redox flow battery.

Heteroatom-doped electrodes offer promising applications for enhancing the longevity and efficiency of vanadium redox flow battery (VRFB). Herein, we controllably synthesized N, P co-doped graphite fiber electrodes with conductive network structure by introducing protonic acid and combining electrodeposition and high temperature carbonization. H2SO4 and H3PO4 act as auxiliary and dopant, respectively. The synergistic effect between N and P introduces additional defect structures and active sites on the electrodes, thereby enhancing the reaction rate, as confirmed by density functional theory calculations. Furthermore, the conductive network structure of carbon fibers improves electrode-to-electrode connectivity and reduces internal battery resistance. The optimized integration of these strategies enhances VRFB performance significantly. Consequently, the N, P co-doped carbon fiber modified graphite felt electrodes demonstrate remarkably high energy efficiency at 200 mA cm-2, surpassing that of the blank battery by 7.9 %. This integrated approach to in-situ controllable synthesis provides innovative insights for developing high-performance, stable electrodes, thereby contributing to advancements in the field of energy storage.

Enhanced photocatalytic performance of NiFe2O4/ZnIn2S4 p-n heterojunction for efficient degradation of tetracycline.

The persistent release of tetracycline into the environment significantly endangers both ecosystems and human health. Zinc indium sulfide (ZnIn2S4) capable to degrade tetracycline pollutants under visible light irradiation has attracted extensive attentions and great effort has been devoted to augment its catalytic efficacy. In this work, we synthesized a p-n heterojunction, NiFe2O4/ZnIn2S4, to enhance the carrier migration rate and explained the intrinsic mechanism by density functional theory. When the heterojunction was formed, carriers traversed from the n-type NiFe2O4 to the p-type ZnIn2S4, instigating the emergence of a built-in electric field to facilitate the separation of carriers. 2 %-NiFe2O4/ZnIn2S4 exhibited excellent photocatalytic efficiency in tetracycline (TC) degradation and total organic carbon (TOC) removal. Compared to pure ZnIn2S4 and NiFe2O4, the TC degradation rates of 2 %-NiFe2O4/ZnIn2S4 were 2.0 times and 16.9 times higher, respectively. Additionally, 2 %-NiFe2O4/ZnIn2S4 had a saturation magnetization intensity of 3.05 emu/g, allowing for rapid recovery of the catalyst under a magnetic field. Superoxide radicals (O2-) and holes (h+) were the primary active species driving the degradation process. Furthermore, potential reaction pathways of tetracycline in this photocatalytic process were determined and bioconcentration factor and developmental toxicity of the intermediate products were accessed. This work held great potentials for wastewater treatment and provided a pathway for the development of magnetic recyclable photocatalysts.

MiR-6721-5p as a natural regulator of Meta-VCL is upregulated in the serum of patients with coronary artery disease.

Background: Coronary artery disease (CAD), the leading cause of mortality globally, arises from atherosclerotic blockage of the coronary arteries. Meta-vinculin (meta-VCL), a large spliced isoform of VCL, co-localizes in muscular adhesive structures and plays significant roles in cardiac physiology and pathophysiology. This study aimed to identify microRNAs (miRNAs) regulating meta-VCL expression and investigate the expression alterations of the miRNAs of interest and meta-VCL as potential biomarkers in the serum of CAD patients. Methods: Bioinformatics tools were employed to select miRNAs targeting meta-VCL. Cell-based ectopic expression analysis and a dual-luciferase assay were used to examine the interactions between miRNAs and meta-VCL. An ELISA assessed the concentrations of interleukin-6 (IL-6), IL-10, and tumor necrosis factor-α (TNF-α). MiRNA and meta-VCL expression patterns and biomarker suitability were evaluated in serum samples from CAD and non-CAD individuals using real-time PCR. A cardiac cell-line data set and CAD blood exosome samples were analyzed using bioinformatics and ROC curve analyses, respectively. Results: miR-6721-5p directly interacted with the putative target sites at the 3'-UTR of meta-VCL and regulated its expression. IL-10 and TNF-α concentrations, which may act as anti-inflammatory factors, decreased following miR-6721-5p upregulation and meta-VCL downregulation. Bioinformatics and experimental expression analyses confirmed downregulated meta-VCL expression and upregulated miR-6721-5p expression in CAD samples. ROC curve analysis yielded an AUC score of 0.705 (P = 0.018), indicating the potential suitability of miR-6721-5p as a biomarker for CAD. Conclusions: miR-6721-5p plays a regulatory role in meta-VCL expression and may contribute to CAD development by reducing anti-inflammatory factors. These findings suggest that miR-6721-5p could serve as a novel biomarker in the pathogenesis of CAD.

Efficiency and mechanism of controlling phosphorus release from sediment using a biological aluminum-based P-inactivation agent.

Eutrophication is a significant challenge for surface water, with sediment phosphorus (P) release being a key contributor. Although biological aluminum-based P-inactivation agent (BA-PIA) has shown effectiveness in controlling P release from sediment, the efficiency and mechanism by BA-PIA capping is still not fully understood. This study explored the efficiency and mechanism of using BA-PIA capping controlling P release from sediment. The main mechanisms controlling P release from sediment via BA-PIA capping involved transforming mobile and less stable fractions into stable ones, passivating DGT-labile P and establishing a 13 mm 'P static layer' within the sediment. Additionally, BA-PIA's impact on Fe redox processes significantly influenced P release from the sediment. After BA-PIA capping, notable reductions were observed in total P, soluble reactive P (SRP), and diffusive gradient in thin-films (DGT)-measured labile P (DGT-labile P) concentration in the overlying water, with reduction rates of 95.6%, 92.7%, and 96.5%, respectively. After BA-PIA capping, the diffusion flux of SRP across the sediment-water interface and the apparent P diffusion flux decreased by 91.3% and 97.8%, respectively. Additionally, BA-PIA capping led to reduced concentrations of SRP, DGT-labile P, and DGT-measured labile Fe(II) in the sediment interstitial water. Notably, BA-PIA capping significantly reduced P content and facilitated transformation in the 0∼30 mm sediment layers but not in the 30∼45 mm and 45∼60 mm sediment layers for NaOH-extractable inorganic P and HCl-extracted P. These findings offer a theoretical basis and technical support for the practical application of BA-PIA capping to control P release from sediment.

Correlation between forkhead box P3 (rs3761548) gene polymorphism and serum interleukin13 as biomarkers of severity in Egyptian allergic conjunctivitis: a retrospective study.

Introduction: The genetic variants that alter human Forkhead Box P3 (FOXP3) function may have a part in the establishment of allergic conjunctivitis. Our study aimed to evaluate the FOXP3 polymorphism, serum interleukin13 (IL13) and total immunoglobulin E (IgE) levels in allergic conjunctivitis and assess their role as biomarkers for allergic conjunctivitis risk and severity. Methods: This study included 52 cases and 52 controls. Blood samples were taken from allergic conjunctivitis patients and controls for total IgE, IL13 measurement and detection of FOXP3 (rs3761548) gene polymorphism. Results: There was a statistically significant difference between the allergic conjunctivitis group and healthy control group regarding FOXP3 (rs3761548) polymorphism with those have AA genotype are 12 times at risk for allergic conjunctivitis and A allele increases the risk of allergic conjunctivitis by about 4 times. There was statistically significant difference between mild/moderate and severe allergic conjunctivitis regarding FOXP3 (rs3761548) polymorphism with those have AA genotype are 53 times at risk for severe allergic conjunctivitis and A allele increases the risk of severe allergic conjunctivitis by about 6 times. Also, there was a significantly higher value of total IgE IU/ml, IL13 Pg/ml value in severe allergic conjunctivitis compared to moderate/mild allergic conjunctivitis. The best cutoff values of total IgE and serum IL13 for detecting the severity of allergic conjunctivitis were ≥320 IU/ml and ≥40 Pg/ml and the area under the curve were 0.89 and 0.95 respectively. Conclusion: The research significantly contributes to find correlation of FOXP3 polymorphism, total IgE and IL13 with risk and severity of allergic conjunctivitis which are limited in the literature on the perceived value relevance of FOXP3 polymorphism in allergic conjunctivitis risk and severity.

C-71980262, a novel small molecule against human papilloma virus-16 E6 (HPV-16 E6) with anticancer potency against cervical cancer: A computational guided in vitro approach.

Objectives: Human papillomavirus-16 E6 (HPV-16 E6) forms a heterodimer complex to up-regulate the degradation of tumor suppressor protein p53 to promote cervical cancer. This study aims to identify a novel small molecule against E6 with anticancer efficacy against HPV-16, a prime high-risk serotype inducer for cervical cancer. Materials and Methods: Autodock-vina-based high-throughput virtual screening and atomistic molecular dynamic simulations were used for identification of targeted lead molecules. HPV-16 infected SiHa and CaSki cell lines were used to validate the lead compound in vitro. Proliferation of cancer cells was analyzed by MTT assay and flow cytometry was used to analyze target inhibition, apoptosis, and p53. Results: High throughput virtual screening and molecular dynamic simulation identified C-71980262 as a lead candidate that could bind HPV-E6. Atomistic molecular dynamic simulation of E6 bound C-71980262 for 200 ns showed that the predicted ligand binding was stable with minimal energy expenditure, proposing the viability and veracity of the assessed molecule. C-71980262 inhibited the proliferation of SiHa and CaSki cells with GI50 values of 355.70 nM and 505.90 nM, respectively. The compound reduced HPV-16 E6 while inducing early and late-phase apoptosis in these cells. Treatment with C-71980262 increased the p53-positive populations in SiHa and CaSki cells. Conclusion: C-71980262 was identified as a novel lead molecule that could inhibit the HPV-16 E6 and increase p53 in cervical cancer cells. Further in vitro and in vivo validation is warranted to consolidate and corroborate this lead compound against HPV-induced cancer progression.

Total flavonoids of Selaginella tamariscina (P. Beauv.) Spring ameliorates diabetes-induced acute lung injury via activating Nrf2/HO-1.

Objectives: This investigation explored the mechanism by which the total flavonoids of Selaginella tamariscina (P.Beauv.) Spring (TFST) mitigate oxidative stress through the activation of the heme oxygenase-1 (HO-1) signaling pathway mediated by nuclear factor erythroid 2-related factor 2 (Nrf2), thereby ameliorating acute lung injury (ALI) induced by diabetes. Materials and Methods: Male mice weighing 20-25 grams were divided into four groups: a control group, a diabetic group, a diabetic group treated with TFST, and a diabetic group treated with TFST and ML385. Various biological specimens were collected for analysis, including bronchoalveolar lavage fluid (BALF), blood, and tissue samples. These were subjected to a range of assessments covering hematological and BALF parameters tumor necrosis factor-alpha (TNF-α), interleukin-6 [IL-6]), biochemical markers (malondialdehyde [MDA], superoxide dismutase [SOD], glutathione peroxidase [GSH], Nrf2, and HO-1 levels), along with histopathological evaluations. Results: Pre-treatment with TFST demonstrated a significant decrease in pulmonary tissue damage, evidenced by decreased wet-to-dry (W/D) lung ratios (P<0.001), reduced lung injury scores (P<0.0001), and lower levels of TNF-α, IL-6 (P<0.0001), as well as oxidative stress markers like MDA (P<0.05). Moreover, there was an elevation in the activity of anti-oxidative enzymes, specifically SOD and GSH (P<0.05), coupled with an enhanced expression of Nrf2 and HO-1 in the diabetic group (P<0.01). Conclusion: The study findings demonstrate that TFST can suppress oxidative stress by modulating the Nrf2 pathway and up-regulating HO-1 activity, thereby ameliorating diabetes-induced acute lung injury.

Comparison of aprepitant versus ondansetron for prevention of postoperative nausea and vomiting: A systematic review and meta-analysis with trial sequential analysis.

Background and Aims: Postoperative nausea and vomiting (PONV) is a common complication after surgery. Preventing PONV in high-risk patients often requires a multimodal approach combining antiemetic drugs with diverse mechanisms. While aprepitant, a neurokinin-1 receptor antagonist, is recognised as highly effective for PONV prevention, uncertainties remain regarding its effectiveness. Methods: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The analysis assessed the effectiveness of aprepitant (A), aprepitant plus ondansetron (AO) and aprepitant plus dexamethasone and ondansetron (ADO) in preventing PONV compared to ondansetron alone (O) or in combination with dexamethasone (DO). Results: In the analysis of 12 studies involving 2729 patients, aprepitant demonstrated significant efficacy in preventing PONV compared to ondansetron alone (A versus [vs.] O: PONV incidence 12.5% vs. 28.5%, relative risk [RR] = 0.45, P < 0.001; complete response rate 55.97% vs. 50.35%, RR = 1.13, P = 0.010). The combination of aprepitant with ondansetron (AO) also showed a significantly lower incidence of PONV compared to ondansetron alone (11.3% vs. 26.8%, RR = 0.43, P < 0.001) and a higher complete response rate (38.1% vs. 26.84%, RR = 1.41, P = 0.020). In addition, ADO significantly reduced PONV incidence compared to DO (ADO vs. DO: 13.63% vs. 35.38%, RR = 0.38, P = 0.006). Conclusion: Aprepitant, whether used alone or in combination with ondansetron or both ondansetron and dexamethasone, consistently outperforms ondansetron in achieving a complete response as it lowers vomiting rates and reduces the need for rescue therapy during the crucial 24-48-h postoperative period.

miRNA375-3p/rapamycin mediates the mTOR pathway by decreasing PS1, enhances microglial cell activity to regulate autophagy in Alzheimer's disease.

The clinical prevention, diagnosis, treatment, and drug development of Alzheimer's disease (AD) require urgent detection of novel targets and methods. Autophagy and microglia are significantly associated with the pathogenesis of early AD. This study indicated that microRNA-375-3p can inhibit autophagy by promoting mTOR phosphorylation in normal physiological conditions, while microRNA-375-3p promoted autophagy and enhanced neural repair by inhibiting the expression of presenilin 1 in early AD pathogenesis. Furthermore, co-treatment of rapamycin, and microRNA-375-3p can synergistically promote the autophagy and microglial activation in a neuroprotective manner, clear Aß accumulation, repair nerve damage, and alleviate cognitive dysfunction and memory defects in APP/PS1 TG mice. This research revealed the impact and mechanism of miR375-3p on the early stage of AD through in vivo and in vitro experiments and provides new ideas and directions for the early treatment of AD.

Melatonin mitigates doxorubicin induced chemo brain in a rat model in a NRF2/p53-SIRT1 dependent pathway.

Cancer is a critical health problem, and chemotherapy administration is mandatory for its eradication. However, chemotherapy like doxorubicin (Dox) has serious side-effects including cognitive impairment or chemo brain. Melatonin is a neuroprotective agent that has antioxidant, and anti-inflammatory effects. We aimed to explore melatonin's effect on Dox-induced chemo brain to discover new mechanisms associated with Dox-induced neurotoxicity and try to prevent its occurrence. Thirty-two male albino rats had been equally divided into four groups; control, melatonin-administrated, Dox-induced chemo brain, and melatonin + Dox treated. On the 9th day, brain had been excised after scarification and had been assessed for reactive oxygen species measurement, histopathological analysis, immunohistochemical, gene and protein expressions for the nuclear factor erythroid 2-related factor 2 (Nrf2), p53 and Silent information regulator 2 homolog 1 (SIRT1). Our results show that melatonin coadministration diminished Dox induced hippocampal and prefrontal cortex (PFC) cellular degeneration. It alleviated Nitric Oxide (NO) level and reversed the decline of antioxidant enzyme activities. It also upregulated Nrf2, SIRT1 and downregulated p53 gene expression in rats receiving Dox. Moreover, melatonin elevated the protein expression level of Nrf2, SIRT1 and reduced p53 corresponding to immunohistochemical results. The data suggested that melatonin can mitigate Dox-induced neurotoxicity by aggravating the endogenous antioxidants and inducing neurogenesis through activation of Nrf2/p53-SIRT1signaling pathway in adult rats' PFC. These effects were associated with Nrf2, SIRT1 activation and p53 inhibition. This could be guidance to add melatonin as an adjuvant supplement to Dox regimens to limit its adverse effect on the brain function.

Coevolutionary Analysis of the Pfs47-P47Rec Complex: A Bioinformatics Approach.

Background: The ability to predict and comprehend molecular interactions offers significant insights into the biological functions of proteins. The interaction between surface protein 47 of Plasmodium falciparum (Pfs47) and receptor of the protein 47 (P47Rec) has attracted increased attention due to their role in parasite evasion of the mosquito immune system and the concept of geographical coevolution between species. The aims of this study were as follows: to apply a bioinformatics approach to investigate the interaction between Pfs47 and P47Rec proteins and to identify the potential binding sites, protein orientations and receptor specificity sites concerning the geographical origins of the vectors and the parasite. Methods: Public sequences of the pfs47 and p47rec genes were downloaded and subsequently filtered to predict functional and structural annotations of the Pfs47-P47Rec complex. Phylogenetic analyses of both proteins were carried out. In addition, the p47Rec gene was subjected to sequencing and subsequent analysis in 2 distinct Anopheles species collected in Honduras. Results: The examination of motifs reveals a significant degree of conservation in pfs47, suggesting that Pfs47 might have undergone recent evolutionary development and adaptation. Structural models and docking analyses supported the theory of selectivity of Plasmodium falciparum strains towards their vectors in diverse geographical regions. A detailed description of the putative interaction between the Pfs47-P47Rec complex is shown. Conclusions: The study identifies coevolutionary patterns between P47Rec and Pfs47 related to the speciation and geographic dispersion of Anopheles species and Plasmodium falciparum, with Pfs47 evolving more recently than P47Rec. This suggests a link between the parasite's adaptability and existing anopheline species across different regions. P47Rec likely has a cytoplasmic localization due to its lack of membrane attachment elements. However, these findings are based on simulations and require validation through methods like cryo-electron microscopy. A significant limitation is the scarcity of sequences in global databases, which restricts precise interaction modelling. Further research with diverse parasite isolates and anopheline species is recommended to enhance understanding of these proteins' structure and interaction.