Ulcerative colitis (UC) is a chronic, non-specific inflammatory disease of the colon that is characterized by complex etiologies, challenging treatment, and high recurrence rate. At present, the main clinical therapeutic agents include suppositories, foams, and liquid enema formulations. But they have problems such as low adhesion and short drug residence time. As a new dosage form, gel has the characteristics of high bioavailability, long drug retention time, high safety and appropriate biological adhesion. This article reviews the relevant literature at home and abroad in the past five years, and analyzes and summarizes the classification of gels, prescription design of various gels, matrix selection, preparation process and pharmacological effects. The results show that the gel can effectively prolong the action time of the drug and alleviate the inflammatory response, which can offer a promising therapeutic strategy for UC management.

Oral liver-targeting nano-drug delivery system is the most potential drug delivery method which has the advantages of good drug compliance, low side effects, and high safety. However, the biological and physiological barriers in the gastrointestinal tract and liver severely hinder the oral absorption and accumulation of drug carriers in the liver lesions. This review first describes the main biological and physiological barriers encountered by the oral liver-targeted nano-drug delivery system during the drug delivery period. Meanwhile, this article summarizes oral liver-targeting drug carriers in recent years. In addition, the research progress of oral liver-targeted nano-drug delivery system in the treatment of liver-related diseases is introduced, which provides ideas for the development of oral liver-targeting nano-drug delivery system in the liver-related disease treatment.

Traditional Chinese medicine contains numerous monomeric active ingredients, which have rich pharmacological effects. However, many of these active ingredients have poor physicochemical properties, making them challenging to use in clinical settings. Cocrystal technology has demonstrated significant potential in enhancing the solubility and bioavailability of these poorly soluble active ingredients. This article provides a comprehensive overview of the current research on cocrystals of active ingredients in traditional Chinese medicine and briefly discusses the relationship between the structures of these active ingredients and the cocrystal formers. The aim is to provide reference for further research on cocrystals of active ingredients of traditional Chinese medicine and their broader applications in the pharmaceutical industry.

The essential requirements of traditional Chinese medicine (TCM) and its identity of drug make it necessary to treat TCM preparations with considerations of clinical practice routines and drug attributes. Quality stability is an elementary drug quality attribute and lays the foundation to guarantee a consistent traditional Chinese medicines (TCMs) efficacy. In light of the complex ingredients of natural sources, the unique medical theory and the safety & efficacy proof from clinical practices, it's hardly possible to objectively evaluate and effectively control TCMs quality using qualitative and quantitative methods with chemical components as references. To ensure efficacy consistency, stable TCMs quality is a prerequisite and thus is regarded as an industrial focus in earnest need of regulatory attention and also the key points and challenge of TCM quality study and assessment. Since the initiation of drug evaluation system reform, Center for Drug Evaluation has devoted to TCM regulatory science study and issued a series of guidelines. These guidelines are established based on characteristics of TCM preparations, scientific principles and actual production situations. Meanwhile, traditional thinking and experience in TCM quality control and modern theories such as "Quality by Design" and "Whole-process Quality Control" were also adopted. As the characteristics of TCM preparations and quality control requirements, this paper analyses the above guidelines, and concludes that these documents have combined TCM clinical experience and drug attributes of safety, efficacy and quality control. They provide guidance for ensuring basic stability of TCM ingredients and reducing batch-to-batch variations. A quality control system that meets the above requirements is established to ensure consistent efficacy of TCM preparations.

Influenza A viruses (IAVs) exhibit rapid mutation and high infectivity, leading to a considerable number of cases and deaths globally. Thus, the development of broad-spectrum inhibitors is of paramount significance. In this study, targeting the hemagglutinin (HA) of IAVs, a set of high-affinity and specific aptamers, namely Apt(HA)-1, Apt(HA)-4, Apt(HA)-9, Apt(HA)-25, and Apt(HA)-93520, were obtained through CE-SELEX. The dissociation constants (K_D) of this group of aptamers [Apts(HA)] with the HA protein were determined by the SPR method to be 25.9, 44.8, 50.7, 54.0, and 45.2 nmol·L^-1, respectively. Apts(HA) can recognize and detect the internationally common influenza virus strains A/PR/8/34 (H1N1) and A/FM/1/47 (H1N1), as well as the clinically isolated Tamiflu-resistant strain A/Liaoningzhenxing/1109/2010 (H1N1), amantadine-resistant strains A/Hunanzhuhui/1222/2010 (H3N2) and A/Fujiantongan/196/2009 (H3N2), and possess broad-spectrum inhibitory effects on influenza viruses. These aptamer inhibitors feature strong in vitro accessibility, good stability, simple structure, and small size. This study not only developed novel broad-spectrum aptamers against IAVs, exerting extensive inhibitory effects on various IAVs, but also paved the way for an effective strategy in the development of universal virus inhibitors.

Seasonal influenza caused by the influenza virus poses a serious threat to human health. The rapid emergence of drug-resistant viral strains and the increasing incidence of novel infectious diseases underscore the urgent need for researchers to develop innovative anti-influenza strategies and drugs. The identification of effective drug combinations and the repurposing of existing drugs have gained traction as a potential avenue for antiviral therapy. This study employed a high-throughput screening system for influenza A virus (IAV) inhibitors to identify drug combinations that exhibit synergistic effects with baloxavir marboxil from FDA-approved and pharmacopeia-listed compound libraries. The results showed that triprolidine, hydroquinine, and mexenone, which individually display limited anti-influenza activity, exhibited synergistic effects when combined with baloxavir marboxil markedly enhancing its anti-IAV potency in cells. Mechanistic studies indicated the synergistic effects of these drug combinations with baloxavir marboxil were not attributed to the inhibition of IAV RNA dependent RNA polymerase (RdRp) activity, suggesting that alternative mechanisms may be responsible for their enhanced effects. This study provides preliminary evidence supporting the feasibility of this drug combination screening strategy and offers a theoretical basis for improving the therapeutic potential of baloxavir marboxil through combination therapy.

Intrahepatic cholangiocarcinoma (ICC), the second most common primary liver malignancy after hepatocellular carcinoma (HCC), has seen a dramatic rise in incidence in recent years without effective therapeutic drugs. Hu Qi San (HQS), an empirical formula developed by professor Qian Ying, a renowned traditional Chinese medicine expert, through years of clinical practice, has demonstrated clinical efficacy in chronic viral hepatitis and primary hepatocellular carcinoma. However, fundamental research on HQS for ICC remains uncleared. Thus, this study utilized a sgp19-KRas mouse model with typical ICC-like lesions and a QBC-939 cell model to evaluate the therapeutic effects of HQS on ICC in vitro and in vivo and elucidate its underlying mechanisms. First, crystal violet staining and EdU assays revealed that HQS significantly inhibited the proliferation and migration of QBC-939 cells (P < 0.05). Subsequently, sgp19-KRas mice were treated with daily oral administration of 20 g·kg^-1 HQS for three weeks. Results demonstrated that HQS effectively suppressed ICC growth and tumor cell proliferation in sgp19-KRas mice, while improving survival rates. Mechanistically, network pharmacology analysis predicted 303 overlapping targets between HQS's active components and ICC-related disease targets, with significant enrichment in the Hippo signaling pathway. The molecular docking results predicted that ononin, calycosin, gallic acid, and taxifolin in HQS can directly bind to Yes-associated protein (YAP). Experimental validation further demonstrated that these four components exhibit in vitro inhibitory effects on QBC-939 cells. Subsequent q-PCR and Western blot analyses of liver tissues from treated sgp19-KRas mice confirmed that HQS inhibited the transcription of YAP, downregulated YAP protein expression, and suppressed the transcription of YAP downstream genes, particularly those in the YAP-Notch pathway. In conclusion, this study demonstrates that HQS exhibits potential therapeutic effects on ICC, and its mechanism of action is closely associated with the YAP-Notch signaling pathway.

In colorectal cancer, tumor necrosis factor receptor-associated factor 2 (TRAF2) is a positive regulator of the Wnt/β-catenin signaling pathway and is closely related to the occurrence and development of colorectal cancer. This study aims to discover novel anti-colorectal cancer small molecules targeting TRAF2 by establishing a high-throughput TRAF2 affinity screening system. The study established and optimized a high-throughput TRAF2 screening system based on Dianthus, and conducted a large-scale screening of 3 716 traditional Chinese medicine (TCM) small molecules from a TCM small molecule library. Microscale thermophoresis (MST) and cellular thermal shift assay (CETSA) were further applied to verify the binding in both purified proteins and living cells. Among the candidates, the strongest binding compound, eupatilin (EUP), had an affinity of 7.87 μmol·L^-1 with TRAF2. TOPFlash assays showed that EUP can inhibit the activity of the Wnt/β-catenin signaling pathway and the growth of colorectal cancer cells and mouse small intestinal adenoma organoids. After TRAF2 was knocked out using CRISPR/Cas9 technology, the inhibitory effect of EUP on the Wnt signaling pathway and colon cancer cells was significantly weakened, indicating that TRAF2 is the functional target protein of EUP. In summary, the novel high-throughput screening method based on Dianthus constructed in this study can be used for the screening of small molecule targeted drugs, and it has been confirmed that EUP is a TRAF2-targeted small molecule that inhibits the development of colorectal cancer, providing a theoretical basis for the development of targeted TRAF2 anti-tumor drugs.

The intestinal barrier, as the primary interface between the body and the external environment, plays a crucial role in sepsis. Methylene blue, with its anti-inflammatory, antioxidant, and microcirculatory-improving properties, has been widely used in the treatment of sepsis. However, whether it can improve intestinal barrier function in sepsis and its underlying mechanisms remain unclear. In the present study, a sepsis mouse model was established via intraperitoneal injection of lipopolysaccharide (LPS). The effects of methylene blue (5-20 mg·kg^-1) on inflammation in septic mice were observed using HE staining, ELISA, and RT-PCR. Changes in intestinal barrier function in the jejunum and colon tissues were analyzed via Evans blue staining, immunofluorescence, and RT-PCR. Additionally, the effects of methylene blue (40 μg·mL^-1) on NF-κB and RhoA/ROCK signaling pathways in LPS-stimulated macrophages (RAW264.7) and intestinal epithelial cells (Caco-2) were evaluated. The animal study was approved by the Animal Ethics Committee of Southwest University (Approval No.: IACUC-20241125-04). Results showed that methylene blue (5-20 mg·kg^-1) significantly reduced the levels of inflammatory cytokines in plasma and intestinal tissues of septic mice and upregulated the expression of tight junction proteins in the jejunum and colon. In vitro experiments confirmed that methylene blue (40 μg·mL^-1) inhibited the increased secretion of inflammatory cytokines in LPS-stimulated RAW264.7 cells, a mechanism associated with NF-κB pathway inhibition. Methylene blue (40 μg·mL^-1) also reversed the LPS-induced decrease in transmembrane electrical resistance and cell migration in Caco-2 cells, a mechanism related to RhoA/ROCK pathway inhibition. In summary, the present study demonstrated that methylene blue can improve intestinal inflammation by inhibiting the NF-κB pathway and enhance intestinal barrier function via the RhoA/ROCK pathway, ultimately alleviating the progression of sepsis.

Enzalutamide resistance (ENZR) is the most common issue in castration-resistant prostate cancer (CRPC). After a period of treatment with the second-generation androgen receptor (AR) inhibitor enzalutamide (ENZ), patients develop resistance to ENZ, posing a serious threat to male health. However, there are currently no effective drugs for treating prostate cancer patients with ENZ resistance. Based on the structural optimization and modification of enzalutamide, and through molecular biological methods such as cell viability assays, colony formation, cell apoptosis detection, Western blot and other molecular biology techniques, it was discovered that the half-maximal inhibitory concentration values of LS-13 for prostate cancer LNCaP-ENZR and 22RV1 cells are 17.09 and 19.90 μmol·L^-1, respectively. Subsequently, after treating the resistant cell lines with 0.1, 1, 5, and 10 μmol·L^-1 of LS-13 for 12 days, the observation results indicated that LS-13 could inhibit the in vitro clonal formation of LNCaP-ENZR and 22RV1 cells in a dose-dependent manner. Furthermore, after treating the resistant cell lines with 1.25, 2.5, 5, and 10 μmol·L^-1 of LS-13 for 72 h, the results of flow cytometry also showed that LS-13 could promote apoptosis of the resistant cell lines in a dose-dependent manner. Furthermore, under the same concentration conditions described above, after LS-13 treatment of 22RV1 cells for 24 h, it was found that their migration speed was significantly slowed down (P < 0.05). These results collectively indicate that the small molecule compound LS-13 has a pronounced effect in inhibiting ENZR. Further mechanism studies found that LS-13 can target ARfl/ARv7 and promote its protein degradation, inhibit the transcription levels of AR-downstream target genes, thereby suppressing ENZR cell proliferation and promoting apoptosis. This study provides a candidate compound for targeting ARfl/ARv7 to overcome ENZ resistance.