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Tuberculosis, a persistent illness caused by Mycobacterium tuberculosis, remains a significant global public health challenge. The widespread use of anti-tuberculosis drugs has resulted in the emergence of drug-resistant strains, which complicates treatment efforts. Addressing this issue is crucial and hinges on the development of new drugs that can effectively target the disease. This involves identifying novel therapeutic targets that can disrupt the bacterium's survival mechanisms in various environments such as granulomas and lesions. Citrate lyase, essential for the survival of Mycobacterium species at lesion sites and in granulomatous conditions, is a potential target for the treatment of tuberculosis. This manuscript aimed to construct an efficient enzyme inhibitor screening platform using ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF MS). This system can accurately identify compounds with enzyme inhibitory activity from a library of marine terpenoids and phenolic compounds. Utilizing the screened herbal enzyme inhibitors as a starting point, we analyzed their chemical structures and skillfully built a library of marine compounds based on these structures. The results showed that all of the tested compounds from the phenolics library inhibited citrate lyase by more than 50%, and a significant portion of terpenoids also demonstrated inhibition, with these active terpenoids comprising over half of the terpenoids tested. The study underscores the potential of marine-derived phenolic and terpenoid compounds as potent inhibitors of citrate lyase, indicating a promising direction for future investigations in treating tuberculosis and associated disorders. [ABSTRACT FROM AUTHOR]

The development of polysaccharide drugs requires a thorough understanding of their quantitative and pharmacokinetic properties. However, the complexity of biological samples presents a challenge for direct analysis using UHPLC-QTOF MS. Therefore, it is essential to establish a method for the selective enrichment of polysaccharides. In this study, we developed an efficient method for the quantitative determination of polysaccharides by integrating magnetic molecularly imprinted polymers (MIPs) for sample pretreatment and UHPLC-QTOF MS for analysis. The MIPs were prepared using molecularly imprinted and boric acid affinity technologies, which combined the advantages of specific recognition and reversible binding to polysaccharides. The MIPs exhibited high dispersibility and uniform particle size, and adsorption experiments demonstrated their specific recognition of BG136, a polysaccharide with immunological activity. The proposed method was used for the purification and enrichment of BG136 in plasma with recoveries between 91.29% and 113.03%. This simple method demonstrated high selectivity, fast separation, and satisfactory recoveries providing an approach for polysaccharide determination with UHPLC-QTOF MS. [ABSTRACT FROM AUTHOR]

The incidence and mortality of cervical cancer in female malignancies are second only to breast cancer, which brings a heavy health and economic toll worldwide. Paclitaxel (PTX)-based regimens are the first-class choice; however, severe side effects, poor therapeutic effects, and difficulty in effectively preventing tumor recurrence or metastasis are unavoidable. Therefore, it is necessary to explore effective therapeutic interventions for cervical cancer. Our previous studies have shown that PMGS, a marine sulfated polysaccharide, exhibits promising anti-human papillomavirus (anti-HPV) effects through multiple molecular mechanisms. In this article, a continuous study identified that PMGS, as a novel sensitizer, combined with PTX exerted synergistic anti-tumor effects on cervical cancer associated with HPV in vitro. Both PMGS and PTX inhibited the proliferation of cervical cancer cells, and the combination of PMGS with PTX displayed significant synergistic effects on Hela cells. Mechanistically, PMGS synergizes with PTX by enhancing cytotoxicity, inducing cell apoptosis and inhibiting cell migration in Hela cells. Collectively, the combination of PTX and PMGS potentially provides a novel therapeutic strategy for cervical cancer. [ABSTRACT FROM AUTHOR]

Tamarixetin and kaempferide, the major bioactive constituents of Xiheliu extract, have been simultaneously/quantitatively determined in rat plasma and urine by a sensitive high performance liquid chromatography method after oral administration the total flavonoids from Xiheliu. In this study, the biological samples were prepared by solid-phase extraction, then simultaneously detected at 254 nm and successfully separated and quantified using a reversed-phase [C.sub.18] column with methanol-formic acid aqueous gradient solution, at a flow rate of 1 mL/min. Good linearity (r > 0.989) of tamarixetin was observed in plasma and urine with the calibration ranges both at 1.6-80 µg/mL. For kaempferide, the correlation coefficient reached 0.994 in plasma at 1.4-70 µg/mL. The RSD of intra- and inter-day were 1.9-6.5% for tamarixetin and 1.3-9.0% for kaempferide in plasma; in urine, the intra- and inter-day RSD for not only tamarixetin but also kaempferide was no more than 7.4 and 5.8%, respectively. The lowest extraction recovery was 87.6% for kaempferide and 93.2% for tamarixetin in plasma and urine for both low and high concentrations. Due to the high sensitivity (the LOQ for tamarixetin was 1.2 µg/mL and for kaempferide 1.4 µg/mL), accuracy, precision, and good selectivity, the assay was successfully applied to pharmacokinetic studies of both flavonols in rats. The half-lives of tamarixetin and kaempferide were 17.8 ± 1.4 and 92.5 ± 1.6 min, and the [c.sub.max] were 3.1 ± 0.2 and 2.5 ± 0.4 µg/mL, respectively. Keywords: tamarixetin, kaempferide, liquid chromatography DOI: 10.1134/S106193481406015X, Tamarix chinensis L. (Chinese name Chengliu) was widely distributed on the beach of Jiangsu province, P. R. China. The twig of Chengliu named Xiheliu, used as a traditional Chinese medicine [...]