Chengdu University of Traditional Chinese Medicine

Zhang M., Xu J., Qu W., Gao J., Mo Y.

Li Q., Ye Z., Wang G., Chen Y., Deng J., Wang D., Wang Y.

Breast cancer (BC) tops the list of causes for female fatalities globally, with the elusive triple-negative breast cancer (TNBC) constituting 10–20% of all cases. Current clinical strategies for combating TNBC encompass a multifaceted approach, including surgical intervention, radiation therapy, chemotherapy, and advanced targeted drugs and immunotherapies. While these modalities have catalyzed significant advancements in TNBC management, lingering limitations continue to pose formidable challenges. There is an acute need for novel therapeutics in the realm of TNBC treatment. Natural products (NPs) have emerged as a rich reservoir for pharmaceutical innovation, owing to their extraordinary range of structures and physicochemical properties. Scholars have reported diverse evidence of NPs’ efficacy against TNBC. This review aims to comprehensively explore the bioactive constituents, specifics and commonalities of chemical structure, and pharmacological mechanisms of NPs, specifically examining their multifaceted roles in impeding TNBC. NPs, which have recently garnered significant interest, are intriguing in terms of their capacity to combat TNBC through multifaceted mechanisms, including the suppression of tumor cell proliferation, the induction of apoptosis, and the inhibition of tumor metastasis. These natural agents primarily encompass a range of compounds, including terpenoids, glycosides, phenolic compounds, and alkaloids. An in-depth exploration has unveiled their involvement in key signaling pathways, including the transforming growth factor-beta (TGF-β), vascular endothelial growth factor A (VEGFA), phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), Wingless/Int-1 (Wnt) /β-catenin, and mitogen-activated protein kinase (MAPK) pathways. Meanwhile, this review also looks at the challenges and opportunities that arise from harnessing natural compounds to influence TNBC, while outlining the prospective trajectory for future research in the field of NPs.

Bi T., Liang P., Zhao Q., Wu J., Zhou Y., Xu Y., Fan X., Yang G., Sun Q., Ren W., Yang Y., Liu Z.

Zhu Y., Wang G., Wang K., Sun M., Zhao L., Zeng Y., Yan C., Ji Y., Hou Y., Li Z., Tao J.

Guo J., Han J., Li F., Ma Q., He J., You F., Ren Y., Fu X.

ABSTRACT Micro-aspiration of oral microorganisms results in considerable enrichment within the lower respiratory tract (LRT), constituting an early event in lung cancer pathogenesis. To explore the correlation between malignant risk of pulmonary nodules (PNs) and oral commensals enrichment in LRT, oral saliva and bronchial alveolar lavage fluid samples from 22 low-risk PN patients, 17 intermediate-risk PN patients, and 11 high-risk PN patients were analyzed using 16S rRNA gene sequencing. Alpha and beta diversity analyses reveal minimal variation in oral microbial diversity and abundance among patients with different risks of PN. In contrast, a significant reduction in the diversity of LRT microbiota is observed in patients at high risk of PN. Based on multigroup comparative analysis of species differences and the linear discriminant analysis effect size method, Synergistes and Tannerella were identified as the dominant bacterial genera in the oral and LRT of high-risk PN patients, respectively. The study found that the LRT microbiota of PN patients seemed to originate from the oral, and the high enrichment of oral microbiota in the lower respiratory tract was most common in high-risk PN patients. The predominant bacterial genera present in the oral cavity and LRT of patients with PN were identified through abundance variance analysis. Eight key microbial genera were found in both the oral cavity and LRT: Streptococcus , Granulicatella , Porphyromonas , Bacillus , Neisseria , Alloprevotella , Prevotella , and Leptotrichia . Notably, receiver operating characteristic analysis identified Streptococcus , Granulicatella , and Leptotrichia as reliable biomarkers to differentiate high-risk PN. Spearman correlation analysis confirmed that the accumulation of oral microorganisms in the LRT played an important role in the process of PN cancerization. The co-occurrence network showed that the coexistence of Veillonella and Streptococcus in the oral and LRT may be involved in the occurrence of PN, while the LRT cluster of Rothia occurred in high-risk PN patients. Correlation analysis among species identified microbial communities predominantly composed of Veillonella , which may facilitate pulmonary carcinogenesis. IMPORTANCE This study is the first to elucidate the composition and interrelationships of oral and lower respiratory tract (LRT) microbiota in patients with pulmonary nodule (PN) across varying malignancy risk levels. We conducted an analysis to investigate the correlation between the malignant potential of PNs and the enrichment of oral microbiota within the LRT. Additionally, we explored the feasibility of utilizing oral-lower respiratory commensal microbiota as biomarkers to assess the benign and malignant nature of pulmonary nodules. This study aims to provide evidence supporting early diagnosis and intervention strategies for lung cancer.

Ji Y., Wang H., He X., Zhu J., Peng C., Zhao Q., Zhan G., Han B.

Yang X., Chen J., Wang Y., Wu Y., Zhang J.

Irinotecan (CPT-11), an inhibitor of DNA topoisomerase I, stands as a pivotal therapeutic agent in oncology. However, its use is primarily constrained by side effects such as neutropenia and the onset of delayed diarrhea. Despite the effective management of neutropenia, CPT-11-induced diarrhea (CID) is often severe, leading to hospitalization, dosage adjustments, and in some cases, treatment discontinuation, which can significantly impact therapeutic outcomes. A multitude of pharmacological agents have been investigated in preclinical and clinical studies with the aim of reducing or preventing the onset of delayed diarrhea associated with CPT-11. This comprehensive review examines the underlying mechanisms of CPT-11-triggered delayed diarrhea and discusses the experimental medications and strategies that have been utilized to combat this adverse effect. This review encompasses an exploration of chemical formulations, the application of traditional Chinese medicine, and the advent of innovative drug delivery systems. It is anticipated that this article will serve as a valuable resource for both novice researchers in the realm of irinotecan chemotherapy and for those who are well-versed in the field, including experts and practicing clinicians.

Lin L., Zhang M., Xie H., Yang M., Zhu T., Yang J., Yang B., Li H.

Abstract Background Viral hepatitis causes annual deaths of 1.4 million people. Antiviral therapy rarely cures the disease, and patients are usually required to maintain lifelong medication, leading to cumulative drug toxicity. Schisandrae Fructus (SF) is efficacious in the treatment of viral hepatitis. Objective The systematic review and meta-analysis aim to examine the efficacy and safety of SF alone or in combination with specific and nonspecific treatments for treating viral hepatitis by analyzing the clinical trials performed up to date. Methods An extensive literature was searched in 7 databases from inception to May 2023. Final outcomes were divided into the primary outcomes containing the total effective rate and virological responses, as well as the secondary outcomes containing liver biochemical functions and frequencies of adverse events. RevMan 5.3 and GRADE pro 3.6 software were used for meta-analysis and assessment of evidence quality. Subgroup analysis was conducted to explore the source of the heterogeneity. Results Twenty-nine randomized controlled trials were included in the meta-analysis. SF treatment was comparable with western medicines or other traditional Chinese treatments in terms of primary and secondary outcomes. In combination with specific treatments with antiviral medicines, SF group reduced 18.45 U/L of alanine aminotransferase levels [weighted mean difference: 18.45, 95% confidence interval (CI): (16.12, 20.78), p < 0.000 01] and 8.37 U/L of aspartate aminotransferase levels [weighted mean difference: 8.37, 95% CI: (1.25, 15.48), p = 0.02], and it decreased the levels of hyaluronic acid (HA) [standard mean difference (SMD): 0.92, 95% CI: (0.58, 1.27), p < 0.000 01], laminin (LN) [SMD: 0.64, 95% CI: (0.38, 0.90), p < 0.000 01], and procollagen type III [SMD: 0.48, 95% CI: (0.28, 0.67), p < 0.000 01], while increasing the total effective rate by 24% [risk ratio: 1.24, 95% CI: (1.15, 1.32), p < 0.000 01]. There were no severe adverse events during treatment. Conclusions SF was a potential adjuvant for antiviral therapy in restoring liver function. However, the poor quality of the included randomized controlled trials limited the recommendations. More long-term, randomized, and double-blind studies should be performed to assess the efficacy and safety of combination therapy.

Yu X., Zhang J., Xu S., Zhou J., Zhuang C., Li J., Zhuang B.

Guilingji capsules (GLJC) have the effect of treating erectile dysfunction (ED). This study aims to explore the potential mechanisms of GLJC in treating ED. We conducted network pharmacology analysis of ED-related targets with GLJC components reported in the TCMSP database and GLJC components reported in the literature, respectively. Molecular docking was employed to validate the binding affinity of these molecular targets. Animal experiments were conducted to validate the aforementioned results. The mechanism of GLJC in treating ED was studied using d-galactose-induced aging rats, and orchiectomized rats were used to investigate further whether the mechanism of GLJC in treating ED is related to androgen. Two network pharmacology analyses indicated that Androgen receptor (AR) and fibroblast growth factor 2 (FGF2) are the candidate targets, suggesting that the mechanism of ED treatment by GLJC may be related to androgens and angiogenesis. Molecular docking further validated the effective binding of GLJC components to these two targets. In animal experiments, GLJC significantly increased the frequency of erections and elevated serum free testosterone levels and penile tissue AR expression in aged rats. GLJC also promoted angiogenesis and inhibited penile tissue fibrosis in aged rats by regulating the expression of FGF2, RICTOR/P-AKT/P-FOXO1. However, such regulation was not observed in orchiectomized rats. Therefore, GLJC increased testosterone utilization in d-galactose-induced aging rats and regulated FGF2, RICTOR/P-AKT/P-FOXO1 signaling pathway in a T-dependent manner, promoting corpus cavernosum survival and angiogenesis. This mechanism led to the inhibition of penile fibrosis.

Xu C., Zhang C., Ganesan K., Chen Q., Tang H., Gao F., Liu Q., Wu J., Sui Y., Li P., Zhang J., Chen J.

Introduction:: Triple-negative breast cancer (TNBC), an aggressive type of breast cancer, remains difficult to treat. Isoliquiritigenin (ISL) is a bioactive compound that is insoluble in water and exhibits significant anti-TNBC activity. Methods:: compound that is insoluble in water and exhibits significant anti-TNBC activity. Method: We previously prepared oral aqueous ISL@ZLH NPs; however, they were less stable in a freezing environment. Hence, the present study aimed to improve the stability of ISL@ZLH NPs using cryoprotectants that can withstand long storage times and are effective in TNBC treatment by creating an efficient oral drug delivery system. Freeze-dried ISL@ZLH NP powder was prepared by solvent evaporation, followed by the addition of trehalose and sucrose. The freeze-dried ISL@ZLH NP pow was optimized and characterized. The anti-TNBC efficacy and pharmacokinetics of the ISL@ZLH NP-pow were examined in plasma and organs, compared with those of aqueous ISL@ZLH NPs. Result:: The ideal particle size of the ISL@ZLH NP pow was 118 nm, which was not filtered out by the glomerulus and allowed the drug to be delivered to the lesions more effectively. Cellular uptake and biodistribution of the ISL@ZLH NP-pow in vivo and in vitro showed prolonged storage in the organs. In addition, cryopreserved ISL@ZLH NP-treated tumors showed significant anti-proliferative and anti-migratory effects through the downregulation of the PI3K-Akt-mToR and MMP2/9 signaling pathways. Conclusion:: These results suggest that oral ingestion of cryopreserved ISL@ZLH NP has the potential for longterm storage and can be employed as a clinical therapeutic approach to treat TNBC.

Liu Z., Zhang J., Li L., Zhang T., Huang L., Yin Q.

Background:: The Shoutai pill (STP) is a classic formulation in traditional Chinese medicine. Preliminary experimental observations from our study suggest that it is effective in enhancing endometrial receptivity. However, the underlying mechanisms by which STP influences endometrial receptivity remain to be elucidated. Purpose:: The objective of this study is to investigate the effects and mechanisms of the STP formulation in enhancing endometrial receptivity in controlled ovarian hyperstimulation (COH) model mice. Methods:: The network pharmacology analysis identified target proteins associated with the reduction of endometrial receptivity by STP. The COH mouse model was established using the GnRHa+PMSG+HCG protocol. The levels of MHC-1 and MHC-2 in mouse serum were measured using the ELISA method, while the levels of IL-1B, IL-4, IL-10, IP-10, IL-1a, IL-2, IL-17, TNF-a, and IFN-y were measured using liquid chip technology. method: The network pharmacology analysis identified target proteins associated with the reduction of endometrial receptivity by STP. The COH mouse model was established using the GnRHa+PMSG+HCG protocol. The levels of MHC-1 and MHC-2 in mouse serum were measured using the ELISA method, while the levels of IL-1B, IL-4, IL-10, IP-10, IL-1a, IL-2, IL-17, TNF-a, and IFN-y were measured using liquid chip technology. Results:: STP exhibited a significant improvement in the immune environment of COH model mice. The major active components of STP were identified as beta-sitosterol and quercetin, among others. Furthermore, AKT1, VEGFA, and several immune factors, such as TNF, IFN, IL1B, and IL10, were identified as key targets for regulating endometrial receptivity. STP enhanced the expression of IL-10, IL-4, and IP-10 in the mice while reducing the expression levels of IL-2, IL-17, TNF-α, and IFN-γ in COH mice. These effects led to the modulation of early high expression of IL-1B and an improvement in endometrial receptivity. Conclusion:: This study demonstrates that STP can modulate in-vivo immune factors throughout the COH process, subsequently restoring the immune equilibrium within the endometrium, thereby enhancing the endometrial receptivity in the COH model mice. conclusion: The findings of this study indicate that STP can improve the endometrial receptivity in COH model mice by regulating the immune factors in their bodies, thus restoring immune balance.

Sheng R., Zhao M., Pu K., Zhou Y., Zeng L., Chen Y., Wang P., Liu X., Xu S.

ABSTRACTAllium macrostemon Bge. (AM) is a widely utilized culinary spice recognized for its numerous health‐promoting properties. Aging‐related cognitive impairment (ARCI) represents a significant global health concern during the aging process. However, the potential of AM to attenuate ARCI has not been investigated. This work aims to reveal the effects and potential mechanisms of the water extraction of AM (WEAM) in alleviating ARCI, with a particular emphasis on the BDNF/TrkB signaling pathway. The findings showed a significant enhancement in memory function and a reduction in hippocampal neuronal damage in aging mice following treatment with WEAM, manifested by an increased spontaneous alternation rate in the Y‐maze, prolonged step‐through latency, and decreased number of errors in the PAT test, a shortened escape latency and increased platform swimming time and platform crossing times in the MWM test. Additionally, WEAM reduced oxidative stress, elevated the expression of proteins related to synaptic plasticity (SYN and PSD95), and activated the BDNF/TrkB signaling pathway in D‐galactose‐induced aging mice. To elucidate the mechanism by which WEAM alleviates ARCI, both a TrkB activator (7,8‐DHF) and an inhibitor (ANA‐12) were employed. The results demonstrated that the effects of WEAM on synaptic plasticity were potentiated by 7,8‐DHF and diminished by ANA‐12. Finally, 11 chemical compositions of WEAM were analyzed and quantified using HPLC‐MS/MS, including macrostemonoside, sarsasapogenin, diosgenin, timosaponin AIII, N‐p‐trans‐coumaroyltyramine, guanosine, adenosine, phenylalanine, adenine, arginine, and valine. These results suggest that AM may serve as a promising culinary spice for mitigating ARCI by promoting the BDNF/TrkB signaling pathway, thereby enhancing synaptic plasticity.

Zhang X., Yang Y., Wen M., Zhong F., Shu X., Xu R., Xiong P., Zhou Z., He X., Tang X., Wang B., Zhou L., Shen T.

Wang D., Wang Y., Zhang S., Yang X., Yang Y., Han T., Luo Y., Shui C., Yang M., Lin Y., Li C.

He C., Li Y., Liu J., Li Z., Li X., Choi J., Li H., Liu S., Li C.

Human papillomavirus (HPV) is the most common virus for genital tract infections. Cervical cancer ranks as the fourth most prevalent cancer globally, with over 99% of cases in women attributed to HPV infection. This infection continues to pose an ongoing threat to public health. Therefore, the development of rapid, high-throughput, and sensitive HPV detection platforms is important, especially in regions with limited access to advanced medical resources. CRISPR-based biosensors, a promising new method for nucleic acid detection, are now rapidly and widely used in basic and applied research and have received much attention in recent years for HPV diagnosis and treatment. In this review, we discuss the mechanisms and functions of the CRISPR-Cas system, focusing on its applications in HPV diagnostics. The review covers CRISPR technologies such as CRISPR-Cas9, CRISPR-Cas12, and CRISPR-Cas13, along with nucleic acid amplification methods, CRISPR-based signal output systems, and point-of-care testing (POCT) strategies. This comprehensive overview highlights the versatility and potential of CRISPR technologies in HPV detection. We also discuss the numerous CRISPR biosensors developed since the introduction of CRISPR to detect HPV. Finally, we discuss some of the challenges faced in HPV detection by the CRISPR-Cas system.