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  1. Xie Y, Jin Z, Ma D, Yin TH, Zhao K
    Bioeng Transl Med, 2023 May;8(3):e10510.
    PMID: 37206211 DOI: 10.1002/btm2.10510
    Nanoparticles (NPs) used for oral administration have greatly improved drug bioavailability and therapeutic efficacy. Nevertheless, NPs are limited by biological barriers, such as gastrointestinal degradation, mucus barrier, and epithelial barrier. To solve these problems, we developed the PA-N-2-HACC-Cys NPs loaded with anti-inflammatory hydrophobic drug curcumin (CUR) (CUR@PA-N-2-HACC-Cys NPs) by self-assembled amphiphilic polymer, composed of the N-2-Hydroxypropyl trimethyl ammonium chloride chitosan (N-2-HACC), hydrophobic palmitic acid (PA), and cysteine (Cys). After oral administration, the CUR@PA-N-2-HACC-Cys NPs had good stability and sustained release under gastrointestinal conditions, followed by adhering to the intestine to achieve drug mucosal delivery. Additionally, the NPs could penetrate mucus and epithelial barriers to promote cellular uptake. The CUR@PA-N-2-HACC-Cys NPs could open tight junctions between cells for transepithelial transport while striking a balance between mucus interaction and diffusion through mucus. Notably, the CUR@PA-N-2-HACC-Cys NPs improved the oral bioavailability of CUR, which remarkably relieved colitis symptoms and promoted mucosal epithelial repair. Our findings proved that the CUR@PA-N-2-HACC-Cys NPs had excellent biocompatibility, could overcome mucus and epithelial barriers, and had significant application prospects for oral delivery of the hydrophobic drugs.
  2. Li Z, Yang L, Xi Z, Yi W, Zeng X, Ma D, et al.
    PLoS One, 2024;19(9):e0310191.
    PMID: 39250467 DOI: 10.1371/journal.pone.0310191
    Intradialytic hypotension (IDH) is common in hemodialysis patients and can lead to several complications. Risk factors for IDH include demographic characteristics, comorbidities, dialysis procedure factors, and so on. Clinical studies on predictive models for dialysis-induced hypotension have shown inconsistent results. This systematic review aims to evaluate published prediction models for IDH, analyzing their characteristics, predictors, efficacy, and the methodological quality and applicability. The protocol has been prepared using the Preferred Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) guidelines. The systematic review protocol for IDH prediction in hemodialysis patients has been registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY2023110081, DOI: 10.37766/inplasy2023.11.0081). A comprehensive search across five major databases (PubMed, Web of Science, Cochrane Library, CNKI, and Wanfang) will be conducted for studies on prediction models of IDH among hemodialysis patients. Two researchers will independently screen literature, extract data, and evaluate the bias risk and applicability of included studies using prediction modelling study tools. This systematic review will provide critical insights into the efficacy and quality of reporting of the IDH model in hemodialysis patients. This will guide clinical staff in selecting the most appropriate IDH prediction model and inform future research endeavors in IDH prediction.
  3. Ma J, Ma NL, Zhang D, Wu N, Liu X, Meng L, et al.
    Chemosphere, 2022 Apr;292:133345.
    PMID: 34922964 DOI: 10.1016/j.chemosphere.2021.133345
    Zero waste multistage utilization of biomass from Ginkgo biloba branches (GBBs) was achieved through extraction of bioactive components, analysis of antioxidant and antibacterial activities, preparation and composition of pyrolyzate, adsorption and reuse of modified biochar. The results showed that GBBs had abundant bioactive components for potential application in the industry of food, chemical raw materials and biomedicine. Especially, the bioactive compounds in acetone extract (10 mg/mL) of GBBs identified by DPPH and ABTS had free radical scavenging abilities of 92.28% and 98.18%, respectively, which are equivalent to Vitamin C used as an antioxidant in food additives. Fourier Transform Infrared and X-Ray Diffraction analysis showed that carboxymethyl cellulose (CMC) and magnetic Fe3O4 were successfully incorporated into raw biochar (RB) to form CMC-Fe3O4-RB nanomaterial. Scanning electron microscopy and X-Ray Diffraction spectroscopy displayed Fe, C, and O existed on the surface of CMC-Fe3O4-RB. Compared with RB, CMC-Fe3O4-RB had a larger specific surface area, pore volume and pore size. Meanwhile, nanomagnetic CMC-Fe3O4-RB solved the problem of agglomeration in traditional magnetized biochar production, and improved the adsorption capacity of Pb2+, which was 29.90% higher than that of RB by ICP-OES. Further, the Pb2+ (10 mg/L) adsorption capacity of CMC-Fe3O4-RB reached the highest level in 2 h at the dosage of 0.01 g/L, and remained stable at 52.987 mg/g after five cycles of adsorption and desorption. This research aided in the creation of a strategy for GBBs zero waste multistage usage and a circular economic model for GBBs industry development, which can be promoted and applied to the fields of food industry and environment improvement.
  4. Liang J, Xiong S, He C, Song Z, Yang S, Ma D, et al.
    Aquat Toxicol, 2023 Dec;265:106774.
    PMID: 38000134 DOI: 10.1016/j.aquatox.2023.106774
    Micro- and nano-plastics (MPs/NPs) are characterized by their small size and extensive surface area, making them global environmental pollutants with adverse effects on organisms at various levels, including organs, cells, and molecules. Freshwater organisms, such as microalgae, emerging plants, zooplankton, benthic species, and fish, experience varying impacts from MPs/NPs, which are prevalent in both terrestrial and aquatic inland environments. MPs/NPs significantly impact plant physiological processes, including photosynthesis, antioxidant response, energy metabolism, and nitrogen removal. Extended exposure and ingestion to MPs/NPs might cause metabolic and behavioral deviations in zooplankton, posing an extinction risk. Upon exposure to MPs/NPs, both benthic organisms and fish display behavioral and metabolic disturbances, due to oxidative stress, neural toxicity, intestinal damage, and metabolic changes. Results from laboratory and field investigations have confirmed that MPs/NPs can be transported across multiple trophic levels. Moreover, MPs/NPs-induced alterations in zooplankton populations can impede energy transfer, leading to food scarcity for filter-feeding fish, larvae of benthic organism and fish, thus jeopardizing aquatic ecosystems. Furthermore, MPs/NPs can harm the nervous systems of aquatic organisms, influencing their feeding patterns, circadian rhythms, and mobility. Such behavioral alterations might also introduce unforeseen ecological risks. This comprehensive review aims to explore the consequences of MPs/NPs on freshwater organisms and their interconnected food webs. The investigation encompasses various aspects, including behavioral changes, alterations in physiology, impacts on metabolism, transgenerational effects, and the disruption of energy transfer within the ecosystem. This review elucidated the physiological and biochemical toxicity of MPs/NPs on freshwater organisms, and the ensuing risks to inland aquatic ecosystems.
  5. Li H, Peng Z, Zhu J, Zhao W, Huang Y, An R, et al.
    BMC Med, 2024 May 16;22(1):199.
    PMID: 38755585 DOI: 10.1186/s12916-024-03409-9
    BACKGROUND: The prospective phase III multi-centre L-MOCA trial (NCT03534453) has demonstrated the encouraging efficacy and manageable safety profile of olaparib maintenance therapy in the Asian (mainly Chinese) patients with platinum-sensitive relapsed ovarian cancer (PSROC). In this study, we report the preplanned exploratory biomarker analysis of the L-MOCA trial, which investigated the effects of homologous recombination deficiency (HRD) and programmed cell death ligand 1 (PD-L1) expression on olaparib efficacy.

    METHODS: HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan-Meier method was utilised to analyse progression-free survival (PFS).

    RESULTS: This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5-22.1) versus 9.2 months (95% CI: 7.5-13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4-18.2) versus 22.2 months (95% CI: 18.3-NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9-NA) versus 8.3 months (95% CI: 6.7-13.8)].

    CONCLUSIONS: HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2.

    TRIAL REGISTRATION: NCT03534453. Registered at May 23, 2018.

  6. Gao Q, Zhu J, Zhao W, Huang Y, An R, Zheng H, et al.
    Clin Cancer Res, 2022 Jun 01;28(11):2278-2285.
    PMID: 35131903 DOI: 10.1158/1078-0432.CCR-21-3023
    PURPOSE: In patients with platinum-sensitive relapsed (PSR) ovarian cancer, olaparib maintenance monotherapy significantly improves progression-free survival (PFS) versus placebo. However, evidence in the Asian population is lacking. This is the first study to evaluate olaparib efficacy and tolerability exclusively in Asian patients with PSR ovarian cancer.

    PATIENTS AND METHODS: Considering the limited placebo effect and significant clinical benefit of olaparib in previous trials, and the rapid approval of olaparib in China, this phase III study was designed as an open-label, single-arm trial. Patients with high-grade epithelial PSR ovarian cancer were enrolled from country-wide clinical centers across China and Malaysia. Patients received oral olaparib (300 mg) twice daily until disease progression or unacceptable toxicity. Primary endpoint was median PFS (mPFS). Primary analysis of PFS using the Kaplan-Meier method was performed when data reached 60% maturity (clinicaltrials.gov NCT03534453).

    RESULTS: Between 2018 and 2020, 225 patients were enrolled, and 224 received olaparib; 35.7% had received ≥3 lines of chemotherapy, 35.3% had achieved complete response to their last line of platinum-based chemotherapy, and 41.1% had a platinum-free interval ≤12 months. At primary data cut-off (December 25, 2020), overall mPFS was 16.1 months; mPFS was 21.2 and 11.0 months in BRCA-mutated and wild-type BRCA subgroups, respectively. Adverse events (AE) occurred in 99.1% of patients (grade ≥3, 48.7%); 9.4% discontinued therapy due to treatment-related AEs.

    CONCLUSIONS: Olaparib maintenance therapy was highly effective and well tolerated in Asian patients with PSR ovarian cancer, regardless of BRCA status. This study highlights the promising efficacy of olaparib in this Asian population. See related commentary by Nicum and Blagden, p. 2201.

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