Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for high-risk hematologic malignancies, yet its efficacy is limited by the onset of graft-versus-host disease (GVHD). Acute GVHD (aGVHD) primarily affects epithelial cells of the gastrointestinal tract, skin, and liver by the involvement of alloreactive T-cells and pro-inflammatory cytokines. The barrier-protective role of hypoxia-inducible factor (HIF), regulated by prolyl hydroxylase, has been significantly implicated in hypoxic inflammatory conditions. In this study, Roxadustat, a prolyl hydroxylase inhibitor, was tested in a murine model of aGVHD (C57BL/6J → BALB/cJ) to decrease hypoxia-mediated early gastrointestinal injury. Recipients were treated with roxadustat or vehicle intraperitoneally daily for the first week post-transplant, and then twice a week till day 42. Roxadustat significantly improves survival by day + 42 with reduced clinical GVHD symptoms. Reduced gut pathology with significant reduction of serum IFN- γ and TNF-α levels, suggesting a decreased systemic inflammation. Roxadustat significantly decreased T-cell infiltration and prevented TNF-α-induced intestinal epithelial cell apoptosis through HIF-1α-dependent repression of Fas-associated death domain protein (FADD) and cleaved caspase 3. In vitro, roxadustat suppressed TNF-α production by peritoneal macrophages and mixed lymphocyte reaction. These results suggest that roxadustat attenuates early gut injury, offering an alternative strategy for acute GVHD following allo-HSCT.

Acute myeloid leukemia is an aggressive and heterogeneous disease characterized by abnormal proliferation of leukemic blast cells and niche remodeling. Traditional therapies fail to manage evolving and resistant AML subtypes. Next-generation immunotherapeutic interventions, such as CAR-T cells, immune checkpoint inhibitors, antibody-drug conjugates, and antibody-based therapeutics, target leukemic blast cells. This review aims to provide a comprehensive overview of the evolving landscapes of immunotherapeutic strategies, challenges, and breakthroughs in tackling AML.

Gamma-glutamyl transpeptidase (GGT) plays a pivotal role in renal glutathione metabolism and redox regulation, and its excessive activation contributes to oxidative stress and tubular injury. Cisplatin (CP) and acetaminophen (Aceta) are well-known nephrotoxic agents primarily inducing renal damage through oxidative mechanisms, whereas amlodipine (Amlo) has been suggested to exert nephroprotective effects. This study aimed to evaluate the protective effect of Amlo against CP- and Aceta-induced nephrotoxicity in rats, with particular emphasis on renal GGT activity and oxidative stress. Fifty-six male albino rats were randomly allocated into seven groups receiving normal saline, CP, Aceta, Amlo, or their respective combinations. Treatments were administered for 14 days, with a single intraperitoneal dose of CP (8 mg/kg) on day 10. Renal GGT activity, oxidative stress markers Reduced Glutathione (GSH), Glutathione Peroxidase (GPx), Catalase (CAT), Superoxide Dismutase (SOD), Malondialdehyde (MDA), and Nitric Oxide (NO), kidney function indices blood urea nitrogen (BUN), serum creatinine (SC), and urea, and histopathological alterations were assessed. Cisplatin markedly elevated renal GGT activity, oxidative stress parameters, and renal dysfunction markers, whereas Aceta induced a milder but significant renal injury. Amlodipine treatment attenuated GGT overactivation, reduced oxidative stress, and improved renal functional and histological integrity, while Aceta co-administration exacerbated CP-induced renal damage. Collectively, these findings indicate that CP induces more pronounced renal GGT activation and oxidative injury than Aceta, and that Amlo confers significant nephroprotection, underscoring the critical role of GGT in drug-induced nephrotoxicity.

Mitochondrial fusion and fission regulate mitochondrial morphology and homeostasis, both of which are essential for maintaining cellular health. Free mitochondria and mitochondrial-containing extracellular vesicles have emerged as key mediators of pathological processes. Conditioning regimens for allogeneic hematopoietic cell transplantation (HCT) damage and lead to impaired mitochondrial function, including biogenesis and respiration, as well as elevated reactive oxygen species (ROS), which contribute to the development of inflammatory conditions as well as activation of antigen presenting cells, the latter being key players in acute graft versus host pathophysiology (GVHD). This leads to increased T-cell activation and proliferation, which increases alloreactivity and drives GVHD. Dysregulated mitochondrial dynamics lead to the release of mitochondrial DNA and formylated peptides, which act as Damage-Associated Molecular Patterns (DAMPs) and trigger cellular homeostatic imbalances, ultimately leading to more inflammation. The understanding that mitochondrial dysfunction contributes to GVHD offers novel therapeutic strategies, including blocking DAMP signaling and modulating immune cell metabolism to restore mitochondrial health. This review aims to understand mitochondrial homeostasis in both recipient and donor cells. This is crucial for understanding GVHD pathophysiology and developing mitochondria-targeted therapies or mitochondrial transfer strategies as potential therapeutic interventions for GVHD.

Acetamiprid (Aceta) is a neonicotinoid insecticide utilized extensively worldwide, and its environmental and human health risks are of concern. Eruca vesicaria is an edible year-round plant that contains a lot of health-promoting phytochemicals and is an excellent source of antioxidants. So, the present investigation was planned to assess the effect of E. vesicaria seed essential oil versus acetamiprid-induced toxicity in rats. Animals were partitioned into 4 groups of seven each: control, E. vesicaria seeds essential oil (ESEO; 0.17 mL/kg), acetamiprid (Aceta; 21.7 mg/kg), and ESEO plus Aceta, respectively. Doses were given orally and daily for 14 days. Results revealed that ESEO has many phytochemical components with high antioxidant activity. Data showed that treatment with Aceta increased lipid peroxidation and decreased the activities of "enzymatic and non-enzymatic antioxidants" in kidney homogenate. Also, disturbance of kidney and liver function biomarkers, lipid profile, and protein content were observed. These are confirmed by the histological, molecular (Cox-2, TNF-α, and PPAR-α), and renal damage biomarkers (KIM-1 and Cystatin C) examination. On the other hand, rats administered ESEO and then treated with Aceta showed significant amelioration in most of the examined indices. To sum up, ESEO has a potent anti-inflammatory, anti-apoptotic, and antioxidant activity that protects against the pronounced harmful effects of Aceta in rat kidneys due to its health-promoting phytochemicals.

Transarterial chemoembolisation (TACE) is standard of care for patients with unresectable hepatocellular carcinoma that is amenable to embolisation; however, median progression-free survival is still approximately 7 months. We aimed to assess whether adding durvalumab, with or without bevacizumab, might improve progression-free survival.

Special populations, like geriatric patients, experience altered paracetamol pharmacokinetics (PK), complicating pain management. More PK research is essential to optimize paracetamol (acetaminophen) dosing. Yet, the reference method ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) is not readily available. Therefore, we aimed to evaluate the agreement between UPLC-MS/MS and the more accessible colorimetric Roche acetaminophen (ACETA) assay in quantifying paracetamol plasma concentrations, to facilitate PK studies and therapeutic drug monitoring for pain management. Patient data and plasma samples were obtained from a prospective study including geriatric patients admitted to the geriatric wards. ACETA and UPLC-MS/MS assays were performed in two separate laboratories. Bland-Altman plot and Passing-Bablok regression were used to assess agreement. Accuracy was evaluated using the McNemar test for a threshold value of 10 mg/L. Population PK modeling was employed to bridge PK data obtained from both methods (NONMEM 7.5). A total of 242 plasma sample pairs were available from 40 geriatric patients (age range, 80-95 years). Paracetamol plasma concentrations from ACETA (median 9.8 [interquartile range 6.1-14.4] mg/L) and UPLC-MS/MS (9.5 [6.2-14.8] mg/L) did not differ significantly (P > 0.05). No significant proportional nor additive bias was observed between both assay methods. The classification accuracy (at threshold 10 mg/L) was 85% (P = 0.414). The conversion factor between ACETA and UPLC-MS/MS was estimated at 1.06 (relative standard error 5%), yet with a 13.4% (relative standard error 23%) interindividual variability. ACETA assay showed no systematic bias in comparison with the UPLC-MS/MS assay in determining paracetamol exposure in geriatric blood samples despite the imprecision.

An improved solid phase extraction (SPE)-high performance liquid chromatography method was established to determine 15 carbonyl compounds, namely, formaldehyde (FOR), acetaldehyde (ACETA), acrolein (ACR), acetone (ACETO), propionaldehyde (PRO), crotonaldehyde (CRO), butyraldehyde (BUT), benzaldehyde (BEN), isovaleraldehyde (ISO), n-valeraldehyde (VAL), o-methylbenzaldehyde (o-TOL), m-methylbenzaldehyde (m-TOL), p-methylbenzaldehyde (p-TOL), n-hexanal (HEX), and 2,5-dimethylbenzaldehyde (DIM), in soil. The soil was ultrasonically extracted with acetonitrile, and the extracted samples were derivatized with 2,4-dinitrophenylhydrazine (2,4-DNPH) to generate stable hydrazone compounds. The derivatized solutions were cleaned using an SPE cartridge (Welchrom® BRP) packed with N-vinylpyrrolidone/divinylbenzene copolymer. Separation was performed on an Ultimate® XB-C18 column (250 mm×4.6 mm, 5 μm), isocratic elution was performed with acetonitrile-water (65∶35, v/v) as the mobile phase, and detection was performed at a wavelength of 360 nm. The 15 carbonyl compounds in the soil were then quantified using an external standard method. The proposed method improves the sample processing method described in the environmental standard HJ 997-2018: Soil and sediment-Determination of carbonyl compounds-High performance liquid chromatography. A series of experiments revealed the following optimal conditions for soil extraction: acetonitrile as the extraction solvent, extraction temperature of 30 ℃, and extraction time of 10 min. The results showed that the purification effect of the BRP cartridge was significantly better than that of the conventional silica-based C18 cartridge. The 15 carbonyl compounds showed good linearities, and all correlation coefficients were above 0.996. The recoveries ranged from 84.6% to 115.9%, the relative standard deviations (RSDs) ranged from 0.2% to 5.1%, and the detection limits were 0.02-0.06 mg/L. The method is simple, sensitive, and suitable for the accurate quantitative analysis of the 15 carbonyl compounds in soil specified in HJ 997-2018. Thus, the improved method provides reliable technical support for studying the residual status and environmental behavior of carbonyl compounds in soil.

This study aimed to examine the side effects of selected neonicotinoids (Acetamiprid, Aceta, and Imidacloprid, Imid) on Oreochromis niloticus juveniles. The acute toxicity, Probit method, revealed an LC50 of 195.81 and 150.76 ppm for Aceta/96 h and Imid/72 h respectively. The fish were divided into three groups that were exposed, for 21 days (n = 5/replicate), to 1/10 of the LC50 of either neonicotinoids, however, the third was an unexposed control group. Results of erythrocytic micronucleus (MN), and nuclear abnormalities (NA) showed that Aceta and Imid exposure caused a significant (p < 0.05) increase in MN by ~ 2.2 and ~ 10 folds, respectively relative to control. NAs occurred at the order of kidney-shaped > budding > binucleated in Aceta, however, budding > binucleated > kidney-shaped was noticed in the Imid group. Histopathological changes in gills, liver, and muscles were observed significantly in both exposed groups with more severity in the Imid group. Collectively, Aceta and Imid have potential genotoxicity and histopathological alterations in O. niloticus.

Lactobacillus plantarum is considered a potential probiotic supplementation for treating obesity. However, the underlying molecular mechanism is poorly understood. Our previous study displayed that L. plantarum FRT4 alleviated obesity in mice fed a high-fat diet (HFD) through ameliorating the HFD-induced gut microbiota dysbiosis. To explore the roles of FRT4 in obesity prevention, in this study, we investigated changes in serum metabolomic phenotype by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) and analyzed the pathway of HFD-fed Kunming female mice orally administered with FRT4 for eight weeks. Using orthogonal partial least squares discriminant analysis (OPLS-DA), metabolite patterns with significant changes were observed. 55 metabolites including phosphatidylcholine, lysophophatidylcholine, sphingomyelin, serotonin, indole-3-methyl aceta, indole-3-carbinol, indole-5,6-quino, 11,12-DHET, prostaglandin B2, leukotriene B4, and 3-hydroxybenzoic acid were identified as potential biomarkers associated with obesity, which were mainly involving in glycerophospholipid metabolism, tryptophan metabolism, and arachidonic acid metabolism. Perturbations of 14 biomarkers could be regulated by FRT4 intervention. These metabolites may serve as valuable biomarkers to understand the mechanisms by which intake of diets containing FRT4 contributes to the treatment or prevention of obesity. Thus, FRT4 can be a promising dietary supplement for the prevention of HFD-induced obesity.

On juveniles of Oreochromis niloticus, the protective potential of ascorbic acid (Asc) against oxidative stress and genotoxicity induced by acetamiprid (Aceta) sub-lethal concentrations was investigated in this study. Fishes were divided into six groups and exposed to either Asc (50 ppm), 10 and 20 ppm Aceta, 10 ppm (Aceta)+Asc, 20 ppm (Aceta)+Asc, or the unexposed control group. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities and their transcripts were assessed. DNA damage in erythrocytes, hepatocytes, and gill cells, in addition to the mitotic index (MI), and the existence of erythrocytic nuclear abnormalities (ENAs) were performed. The results showed that concentrations of Aceta (10 and 20 ppm) induced oxidative stress by altering the antioxidant enzyme activities and transcripts. There were genotoxic effects of Aceta exposure showed by the significant (P < 0.05) increase in DNA-damaged cells and ENA, meanwhile a decrease in MI. Co-exposure with Asc showed significant alleviations of oxidative status and genotoxicity. Thus, results suggest that Asc-combined exposure could be the effective treatment against Aceta-induced oxidative stress accompanied with genotoxicity in O. niloticus.