Colon-targeted hydroxyethyl starch-curcumin microspheres with high loading capacity ameliorate ulcerative colitis via alleviating oxidative stress, regulating inflammation, and modulating gut microbiota.

Curcumin (CUR) is a natural polyphenol that holds promise for treating ulcerative colitis (UC), yet oral administration of CUR exhibits limited bioavailability and existing formulations for oral delivery of CUR often suffer from unsatisfactory loading capacity. This study presents hydroxyethyl starch-curcumin microspheres (HC-MSs) with excellent CUR loading capacity (54.52 %), and the HC-MSs can further encapsulate anti-inflammatory drugs dexamethasone (DEX) to obtain a combination formulation (DHC-MSs) with high DEX loading capacity (19.91 %), for combination therapy of UC. The microspheres were successfully engineered, retaining the anti-oxidative and anti-inflammatory activities of parental CUR and demonstrating excellent biocompatibility and controlled release properties, notably triggered by α-amylase, facilitating targeted drug delivery to inflamed sites. In a mouse UC model induced by dextran sulfate sodium, the microspheres effectively accumulated in inflamed colons and both HC-MSs and DHC-MSs exhibited superior therapeutic efficacy in alleviating UC symptoms compared to free DEX. Moreover, mechanistic exploration uncovered the multifaceted therapeutic mechanisms of these formulations, encompassing anti-inflammatory actions, mitigation of spleen enlargement, and modulation of gut microbiota composition. These findings underscore the potential of HC-MSs and DHC-MSs as promising formulations for UC, with implications for advancing treatment modalities for various inflammatory bowel disorders.

The first case of intellectual disability caused by novel compound heterozygosity for NUDT2 variants.

NUDT2 is an enzyme important for maintaining the intracellular level of the diadenosine tetraphosphate (Ap4A). Bi-allelic loss of function variants in NUDT2 has recently been reported as a rare cause of intellectual disability (ID). Herein, we describe a Chinese girl with ID, attention deficit hyperactivity disorder (ADHD), and motor delays with abnormal walking posture and difficulty climbing stairs, who bears compound heterozygous variants c.34 C > T (p.R12*) and c.194T > G (p.I65R) in NUDT2. Homozygous variants c.34 C > T (p.R12*) or c.186del (p.A63Qfs*3) in NUDT2 were previously reported to cause ID. This is the first patient with ID due to compound heterozygous variants in NUDT2 and p.I65R is a novel missense variant. This study enriched the genotype and phenotype of NUDT2-related ID and supported the critical developmental involvement of NUDT2.

Infectious mononucleosis in children and differences in biomarker levels and other features between disease caused by Epstein-Barr virus and other pathogens: a single-center retrospective study in China.

Background: Infectious mononucleosis (IM) is a common viral infection that typically presents with fever, pharyngitis and cervical lymphadenopathy. Our aim was to identify the different pathogens causing IM in children admitted to our hospital and to analyze the differences in features of infection with different organisms. Methods: We retrospectively analyzed the data of children aged 0-17 years admitted to Wuhan Children's Hospital during 2013-2022 with IM. We compared symptoms, physical findings, blood counts, and serum biomarkers between patients with IM due to Epstein-Barr virus (EBV) and IM due to other pathogens. Results: Among 1480 enrolled children, 1253 (84.66%) had EBV infection, 806 (54.46%) had M. pneumoniae infection, 796 (53.78%) had cytomegalovirus infection, 159 (10.74%) had parvovirus infection, 38 (2.57%) had influenza virus infection, and 25 (1.69%) had adenovirus infection. Receiver operating characteristic curves were used to determine the area under the curve for alanine transaminase (ALT), aspartate transaminase (AST), Alkaline phosphatase (ALP), total bilirubin (TBil), indirect bilirubin (IBil) levels to assess liver damage, and for creatine kinase (CK), CK-MB, and lactate dehydrogenase (LDH) levels to assess myocardial damage. The optimal cutoff values of these biomarkers were then determined. In multivariate analysis, elevated ALT, AST, ALP, TBil, and IBil were independently associated with liver damage, and age <3 years, CK, CK-MB, and LDH with myocardial damage. Conclusion: Evaluation of biomarkers and pathogen detection may help physicians to take preventive actions to avoid serious complications in children with infectious mononucleosis.

Risk prediction of dysthyroid optic neuropathy based on CT imaging features combined the bony orbit with the soft tissue structures.

Purpose: To analyze computed tomographic (CT) imaging features of patients with dysthyroid optic neuropathy (DON) retrospectively and deduce a more appropriate predictive model. Methods: The CT scans and medical records of 60 patients with clinically proven Graves' ophthalmopathy (GO) with (26 women and 10 men) and without DON (16 women and 8 men) were retrospectively reviewed, and 20 age- and sex-matched control participants (12 women and 8 men) were enrolled consecutively. The bony orbit [orbital rim angle (ORA), medial and lateral orbital wall angles (MWA and LWA), orbital apex angle (OAA), and length of the lateral orbital wall (LWL)], and the soft tissue structures [maximum extraocular muscle diameters (Max EOMD), muscle diameter index (MDI), medial and lateral rectus bulk from inter-zygomatic line (MRIZL and LRIZL), proptosis, intraorbital optic nerve stretching length (IONSL), superior ophthalmic vein diameter (SOVD), apical crowding, and presence of intracranial fat prolapse] were assessed on a clinical workstation. The CT features among groups were compared, and a multivariate logistic regression analysis was performed to evaluate the predictive features of DON. Results: All bony orbital angle indicators, except ORA (p = 0.461), were statistically different among the three groups (all p < 0.05). The values of MWA, LWA, OAA, and LWL were larger in the orbits with the DON group than in the orbits without the DON group (all p < 0.05). The MDI, MRIZL, proptosis, IONSL, and SOVD were statistically significantly different among the three groups (all p < 0.05), in which the orbits with the DON group were significantly higher than the orbits without the DON group and control group. The apical crowding was more severe in the orbits with the DON group than in the orbits without the DON group (p = 0.000). There were no significant differences in the LRIZL and the presence of intracranial fat prolapse (all p > 0.05). The multivariate regression analysis showed that the MWA, MDI, and SOVD were the independent factors predictive of DON. The sensitivity and specificity for the presence of DON by combining these three indicators were 89 and 83%, respectively. Conclusion: Bone and soft tissue CT features are useful in the risk prediction of DON, especially the MWA, MDI, and SOVD were the independent factors predictive of DON.

Colon-targeted oral nanoparticles based on ROS-scavenging hydroxyethyl starch-curcumin conjugates for efficient inflammatory bowel disease therapy.

Co-delivery of anti-inflammatory drugs and reactive oxygen species (ROS) scavengers by stimuli-responsive oral nanoparticles is deemed to be a favorable strategy for inflammatory bowel disease (IBD) therapy. In this study, using micelles formed by CUR conjugated hydroxyethyl starch (HES) as vehicles, dexamethasone (DEX)-loaded HES-CUR nanoparticles (DHC NPs) with desirable size, negative surface charge, good stability in the harsh gastric environment, and excellent ROS scavenging activity are developed as a colon-targeted oral formulation for treating IBD. Due to the degradation of HES in response to α-amylase overexpressed in the inflamed colon, the DHC NPs release drugs in an α-amylase-responsive manner. Meanwhile, the DHC NPs can be effectively internalized by macrophages and show excellent cytocompatibility with macrophages since they are composed of food-derived compounds. Importantly, in vivo studies reveal that the DHC NPs are capable of targeting the inflamed colon induced by dextran sulfate sodium (DSS), and the targeted and combination therapy enhances the efficacy of free DEX and significantly relieves the impairment caused by DSS-induced ulcerative colitis. Incorporating the merits of targeted drug delivery and combined therapy with an anti-inflammatory drug and ROS scavenger, the DHC NPs are promising for developing novel oral formulations for IBD therapy.