Treatment of Netherton Syndrome in Pediatrics with Upadacitinib.

Background: Netherton syndrome, a rare autosomal recessive genetic disease, lacks effective treatment options. This article presents a novel case of successful Upadacitinib therapy in a 14-year-old boy with Netherton syndrome. Case Presentation: A 14-year-old male with a lifelong history of dry skin, erythema, scaling, itching, and notable body odor was evaluated. These symptoms, accompanied by irregular hair growth and delayed development, prompted an initial diagnosis of atopic dermatitis at a local hospital. Treatment with antihistamines, moisturizers, and topical corticosteroids failed to alleviate systemic manifestations of red patches and persistent itching. Seeking further evaluation, the patient was presented to our center. Upon examination, the characteristics of "bamboo hair" and "golf tee sign" were observed microscopically in the patient's hair. Whole exome sequencing identified a paternally inherited mutation in the SPINK5 gene, confirming Netherton syndrome. No mutations were found in the mother. Despite initial positive responses to Secukinumab and Dupilumab, therapeutic efficacy waned over time. Results and Conclusions: Initiation of Upadacitinib at a daily dose of 15 mg yielded significant therapeutic benefits within a short timeframe. This study marks the first documented use of Upadacitinib in pediatric Netherton syndrome treatment. This case highlights the efficacy of Upadacitinib in treating Netherton syndrome, particularly in pediatric patients. Further studies are warranted to elucidate its long-term effects and optimal dosing regimens.

Efficacy and safety of Ginkgo biloba extract as an adjuvant in the treatment of Chinese patients with sudden hearing loss: a meta-analysis.

CONTEXT: Ginkgo biloba Linn (Ginkgoaceae) [leaves extract (GBE)] is authorized for the treatment of sudden hearing loss (SHL); however, its clinical feasibility in SHL has not been thoroughly investigated. OBJECTIVE: To evaluate the efficacy and safety of adjuvant GBE in the treatment of SHL. MATERIALS AND METHODS: We used PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang, Chinese Scientific Journal Database, China Biomedical Database for literature research, starting from inception to 30 June 2022. The key terms: Ginkgo biloba extract, Sudden Sensorineural Deafness. This meta-analysis contained randomized controlled trials that compared the safety and efficacy of the combination of GBE and general treatments (GT) with GT alone for SHL. The extracted data were analyzed using Revman5.4 software with risk ratio (RR), 95% confidence intervals (CI) and mean difference (MD). RESULTS: Our meta-analysis included 27 articles with a total of 2623 patients. The results revealed that the effects of GBE adjuvant therapy was superior than GT (total effective rate: RR = 1.22, 95% CI: 1.18-1.26, p < 0.00001), the pure tone hearing threshold (MD = 12.29, 95% CI: 11.74-12.85, p < 0.00001) and hemorheology indexes (whole blood high shear viscosity: MD = 1.46, 95% CI: 0.47-2.44, p = 0.004) after treatment were significantly improved compared to non-treatment, while there was no significant difference as for hematocrit (red blood cells) (MD = 4.15, 95% CI: -7.15-15.45, p = 0.47). CONCLUSION: The efficacy of GBE + GT for the treatment of SHL may be more promising than GT alone.

Dihydromyricetin Improves Cognitive Impairments in d-Galactose-Induced Aging Mice through Regulating Oxidative Stress and Inhibition of Acetylcholinesterase.

SCOPE: Alzheimer's disease (AD) is a neurodegenerative disease with phenomena of cognitive impairments. Oxidative stress and cholinergic system dysfunction are two widely studied pathogenesis of AD. Dihydromyricetin (DMY) is a natural dihydroflavonol with many bioactivities. In this study, it is aimed to investigate the effects of DMY on cognitive impairment in d-galactose (d-gal) induced aging mice. METHODS AND RESULTS: Mice are intraperitoneally injected with d-gal for 16 weeks, and DMY is supplemented in drinking water. The results show that DMY significantly improves d-gal-induced cognitive impairments in novel object recognition and Y-maze studies. H&E and TUNEL staining show that DMY could improve histopathological changes and cell apoptosis in mice brain. DMY effectively induces the activities of catalase, superoxide dismutase and glutathione peroxidase, and reduces malondialdehyde level in mice brain and liver. Furthermore, DMY reduces cholinergic injury by inhibiting the activity of Acetylcholinesterase (AChE) in mice brain. In vitro studies show that DMY is a non-competitive inhibitor of AChE with IC50 value of 161.2 µg mL-1 . CONCLUSION: DMY alleviates the cognitive impairments in d-gal-induced aging mice partly through regulating oxidative stress and inhibition of acetylcholinesterase.

Physicochemical properties of dihydromyricetin and the effects of ascorbic acid on its stability and bioavailability.

BACKGROUND: Dihydromyricetin (DMY) is a natural dihydroflavonol with many bioactive effects. However, the physicochemical properties of DMY related to its bioavailability, especially its stability, are unclear. RESULTS: The effects of pH, temperature, metal ions and ascorbic acid (AA) on the stability of DMY were studied using high-performance liquid chromatography (HPLC). The bioavailability of DMY in the presence and absence of AA was compared. Dihydromyricetin was unstable in weak alkaline solutions, and the degradation was significantly accelerated in the presence of Cu2+ and Fe3+ . The degradation process followed the first-order kinetic model. The degradation rate constant (k) increased with increasing pH and temperature. The remaining DMY was only 49% of its initial concnentration after 4 h in simulated intestinal fluid (SIF) at 37 °C. However, by supplementing with AA, the degradation of DMY was rarely occured within 6 h. The solubility of DMY at pH 3-5 was about 750 µg mL-1 , slightly increasing to 853 µg mL-1 at pH 6. Pharmacokinetic studies showed that the bioavailability of DMY increased from 0.122% to 0.341% by supplementing with AA (10% of DMY). CONCLUSION: The degradation of DMY is one reason for its poor bioavailability. The presence of AA could significantly improve the stability of DMY, and further improve its bioavailability in rats. © 2020 Society of Chemical Industry.

Metabolism, Excretion, and Tissue Distribution of Astilbin-Zein Nanoparticles in Rats.

The excretion, tissue distribution, and metabolic profile of astilbin in rat were studied by HPLC and UPLC-QTOF-MS. Astilbin underwent isomerization in the small intestine, and its four isomers were found in feces. Besides, taxifolin, the aglycone of astilbin, and its further metabolites by gut microbes through hydrogenation, dehydration, and ring-fission were found. The total feces excretion of astilbin was about 14.4% of administration. The forming of zein-caseinate nanoparticles can significantly delay and reduce the feces excretion of astilbin. Astilbin and its isomers were absorbed in their intact form. The main metabolites found in plasma and tissues were the methylated products. Astilbin was rapidly distributed in various tissues including brain and maintained relatively high concentration in heart. Compared with other tissues, significantly higher concentration and longer duration of astilbin were found in the gastrointestinal tract. Astilbin and its isomers were excreted in their intact and methylated form in urine.

Facile synthesis of fluorescent carbon dots from Prunus cerasifera fruits for fluorescent ink, Fe3+ ion detection and cell imaging.

Carbon dots (CDs) synthesized from natural products have drawn numerous attentions due to some unique properties. Here, Prunus cerasifera fruits were used as carbon source to synthesize high luminescent CDs by hydrothermal method. The obtained CDs were characterized by TEM, FTIR and XPS methods, founding the CDs were near-spherical and contained abundant nitrogen element. The CDs aqueous solution exhibited bright blue fluorescence under ultraviolet illumination, with the maximum emission at 450 nm. They could be potentially used as invisible fluorescent ink by written on the paper and irradiated by UV light, due to their fluorescent properties. Moreover, the CDs were found being selectively quenched by Fe3+ ion. The quench of CDs was linearly related to the concentration of Fe3+ ion in the range of 0-0.5 mM, meaning they could be developed as fluorescent probe of Fe3+ ion. At last, the CDs were used for cell imaging, founding they were low toxicity to HepG2 cells and exhibited blue and green fluorescence under a fluorescence microscope. In summary, the CDs prepared from Prunus cerasifera fruits exhibited excellent fluorescence properties, and could be potentially applied in the field of fluorescent ink, Fe3+ ion detection and cell imaging.

Quantifying Aflatoxin B1 in peanut oil using fabricating fluorescence probes based on upconversion nanoparticles.

Rare earth doped upconversion nanoparticles convert near-infrared excitation light into visible emission light. Compared to organic fluorophores and semiconducting nanoparticles, upconversion nanoparticles (UCNPs) offer high photochemical stability, sharp emission bandwidths, and large anti-Stokes shifts. Along with the significant light penetration depth and the absence of autofluorescence in biological samples under infrared excitation, these UCNPs have attracted more and more attention on toxin detection and biological labelling. Herein, the fluorescence probe based on UCNPs was developed for quantifying Aflatoxin B1 (AFB1) in peanut oil. Based on a specific immunity format, the detection limit for AFB1 under optimal conditions was obtained as low as 0.2ng·ml(-1), and in the effective detection range 0.2 to 100ng·ml(-1), good relationship between fluorescence intensity and AFB1 concentration was achieved under the linear ratios up to 0.90. Moreover, to check the feasibility of these probes on AFB1 measurements in peanut oil, recovery tests have been carried out. A good accuracy rating (93.8%) was obtained in this study. Results showed that the nanoparticles can be successfully applied for sensing AFB1 in peanut oil.