Molecular mechanism of miRNA mediated biosynthesis of secondary metabolites in medicinal plants.

Plant secondary metabolites are important raw materials for the pharmaceutical industry, and their biosynthetic processes are subject to diverse and precise regulation by miRNA. The identification of miRNA molecules in medicinal plants and exploration of their mechanisms not only contribute to a deeper understanding of the molecular genetic mechanisms of plant growth, development and resistance to stress, but also provide a theoretical basis for elucidating the pharmacological effects of authentic medicinal materials and constructing bioreactors for the synthesis of medicinal secondary metabolite components. This paper summarizes the research reports on the discovery of miRNA in medicinal plants and their regulatory mechanisms on the synthesis of secondary metabolites by searching the relevant literature in public databases. It summarizes the currently discovered miRNA and their functions in medicinal plants, and summarizes the molecular mechanisms regulating the synthesis and degradation of secondary metabolites. Furthermore, it provides a prospect for the research and development of medicinal plant miRNA. The compiled information contributes to a comprehensive understanding of the research progress on miRNA in medicinal plants and provides a reference for the industrial development of related secondary metabolite biosynthesis.

Two-stream vision transformer based multi-label recognition for TCM prescriptions construction.

Traditional Chinese medicine (TCM) observation diagnosis images (including facial and tongue images) provide essential human body information, holding significant importance in clinical medicine for diagnosis and treatment. TCM prescriptions, known for their simplicity, non-invasiveness, and low side effects, have been widely applied worldwide. Exploring automated herbal prescription construction based on visual diagnosis holds vital value in delving into the correlation between external features and herbal prescriptions and offering medical services in mobile healthcare systems. To effectively integrate multi-perspective visual diagnosis images and automate prescription construction, this study proposes a multi-herb recommendation framework based on Visual Transformer and multi-label classification. The framework comprises three key components: image encoder, label embedding module, and cross-modal fusion classification module. The image encoder employs a dual-stream Visual Transformer to learn dependencies between different regions of input images, capturing both local and global features. The label embedding module utilizes Graph Convolutional Networks to capture associations between diverse herbal labels. Finally, two Multi-Modal Factorized Bilinear modules are introduced as effective components to fuse cross-modal vectors, creating an end-to-end multi-label image-herb recommendation model. Through experimentation with real facial and tongue images and generating prescription data closely resembling real samples. The precision is 50.06 %, the recall rate is 48.33 %, and the F1-score is 49.18 %. This study validates the feasibility of automated herbal prescription construction from the perspective of visual diagnosis. Simultaneously, it provides valuable insights for constructing herbal prescriptions automatically from more physical information.

Screening of natural inhibitors against peptidyl arginine deiminase 4 from herbal extracts by a high-performance liquid chromatography ultraviolet-visible based method.

Peptidyl arginine deiminase 4 (PAD4) is an important biocatalytic enzymes involved in the conversion of protein arginine to citrulline, its dysregulation has a great impact on many physiological processes. Recently, PAD4 has emerged as a potential therapeutic target for the treatment of various diseases including rheumatoid arthritis (RA). Traditional Chinese Medicines (TCMs), also known as herbal plants, have gained great attention by the scientific community due to their good therapeutic performance and far fewer side effects observed in the clinical treatment. However, limited researches have been reported to screen natural PAD4 inhibitors from herbal plants. The color developing reagent (COLDER) or fluorescence based methods have been widely used in PAD4 activity assay and inhibitor screening. However, both methods measure the overall absorbance or fluorescence in the reaction solution, which are easy to be affected by the background interference due to colorful extracts from herbal plants. In this study, a simple, and robust high-performance liquid chromatography ultraviolet-visible (HPLC-UV) based method was developed to determine PAD4 activity. The proposed strategy was established based on COLDER principle, while used hydrophilic l-arginine instead of hydrophobic N-benzoyl-l-arginine ethyl ester (BAEE) as a new substrate to determine PAD4 inhibition activity of herbal extracts. The herbal extracts and PAD4 generated hydrophobic l-citrulline were successfully separated by the HPLC, and the developed method was optimized and validated with a known PAD4 inhibitor (GSK484) in comparison with COLDER assay. The IC50 value of GSK484 measured by HPLC-UV method was 153 nM, and the detection limit of the citrulline was 0.5 nmol, respectively, with a linear range of 0.5 nmol to 20 nmol. The IC50 value of the HPLC-UV method was improved by nearly three times compared with COLDER assay (527 nM), and the results indicated the reliability of PAD4 inhibition via HPLC-UV method. The inhibitory effect against PAD4 were fast and accurately screened for the twenty-four extracts from eight herbs. Among them, Ephedra Herba extracts showed significant inhibitory activity against the PAD4 with the IC50 values of three extracts (ethanol, ethyl acetate and water) ranging from 29.11 µg/mL to 41.36 µg/mL, which may help researchers to discover novel natural compounds holding high PAD4 inhibition activity.

The Therapeutic Effect of Laparoscopic Combined with Plasma Electric Cutting Knife on Patients with Rectal Cancer and its Impact on Serum Inflammatory Factors: A Retrospective Study.

Objective: This study investigated the therapeutic effect of laparoscopic surgery combined with the plasma electric cutting knife on patients diagnosed with rectal cancer and its impact on serum inflammatory factors in the bloodstream. Methods: The researchers examined the clinical data of 85 patients who underwent laparoscopic low anterior resection for rectal cancer in our hospital from April 2020 to December 2021. The patients comprised two groups: an observation group of 40 cases and a control group of 45 cases. The CD3+, CD4+, CD8+, and CD4+/CD8+ levels in both groups were detected using flow cytometry. The levels of relevant inflammatory factors in serum were measured using an automatic biochemical analyzer. The researchers then compared the perioperative outcomes between the two groups. Results: The observation group demonstrated significantly shorter duration for the first time passing gas after surgery (P = .029) and hospital stays (P = .002) than the control group. Both groups experienced decreased levels of CD8+ cells following treatment, with the observation group exhibiting lower levels than the control group (P < .05). After three months of treatment, both groups showed reduced levels of relevant serum inflammatory factors, TNF-α, IL-1, IL-6, and IL-8; however, the observation group was significantly lower than the control group with statistical significance (P < .05). Similarly, after three months of treatment, both groups exhibited lower levels of relevant serum electrolytes K+, Na+, and Cl-, with the observation group having lower levels than the control group (P < .05). Throughout the 12-month follow-up period, the two groups had no significant differences (P > .05) in complications such as urinary tract infection, anastomotic leakage, or anastomotic bleeding. Conclusion: Using a combination of laparoscopic techniques and a plasma electric cutting knife proved a highly effective surgical approach in treating rectal cancer. The method has numerous advantages, such as enhanced safety and few complications. When considering perioperative complications, it was evident that laparoscopic combined with the plasma electric cutting knife surpassed other surgical methods in treating rectal cancer.

The role and mechanism of TCM in the prevention and treatment of infectious diseases.

The constant presence of infectious diseases poses an everlasting threat to the entire world. In recent years, there has been an increased attention toward the application of traditional Chinese medicine (TCM) in the treatment of emerging infectious diseases, as it has played a significant role. The aim of this article is to provide a concise overview of the roles and mechanisms of TCM in treating infectious diseases. TCM possesses the ability to modulate relevant factors, impede signaling pathways, and inhibit microbial growth, thereby exhibiting potent antiviral, antibacterial, and anti-inflammatory effects that demonstrate remarkable efficacy against viral and bacterial infections. This article concludes that the comprehensive regulatory features of Chinese herbal medicines, with their various components, targets, and pathways, result in synergistic effects. The significance of Chinese herbal medicines in the context of infectious diseases should not be underestimated; however, it is crucial to also acknowledge their underutilization. This paper presents constructive suggestions regarding the challenges and opportunities faced by Chinese medicines. Particularly, it emphasizes the effectiveness and characteristics of Chinese medicines in the treatment of infectious diseases, specifying how these medicines' active substances can be utilized to target infectious diseases. This perspective is advantageous in facilitating researchers' pharmacological studies on Chinese medicines, focusing on the specific points of action. The mechanism of action of Chinese herbal medicines in the treatment of infectious diseases is comprehensively elucidated in this paper, providing compelling evidence for the superior treatment of infectious diseases through Chinese medicine. This information is favorable for advancing the development of TCM and its potential applications in the field of infectious diseases.

Simultaneous determination of six α-dicarbonyl compounds in traditional Chinese medicines using high-performance liquid chromatography-fluorescence detector with pre-column derivatization.

A reliable method for determination of six α-dicarbonyl compounds in traditional Chinese medicines was first developed and validated by high-performance liquid chromatography-fluorescence detector with pre-column derivatization. α-Dicarbonyl compounds in traditional Chinese medicines were extracted and derivatized with 2,3-diaminaphthalene. The derivatization procedure of six α-dicarbonyl compounds was confirmed by high-resolution mass spectrometry. The limits of quantitation for six α-dicarbonyl compounds ranged from 3.70 × 10-3 to 2.21 × 10-2  µM. The established method showed good linearity (regression coefficient > 0.9990), precision (relative standard deviation < 3.37%), and high recovery (97.8%∼113.1%). The developed method was successfully applied to detect the six α-dicarbonyl compounds in traditional Chinese medicines. The result exhibited six α-dicarbonyl compounds was found in the 15 kinds of traditional Chinese medicines, which suggested us that the determination of α-dicarbonyl compounds should be paid more attention in the quality control of traditional Chinese medicines.

TCM Prescription Generation via Knowledge Source Guidance Network Combined with Herbal Candidate Mechanism.

Traditional Chinese medicine (TCM) prescriptions have made great contributions to the treatment of diseases and health preservation. To alleviate the shortage of TCM resources and improve the professionalism of automatically generated prescriptions, this paper deeply explores the connection between symptoms and herbs through deep learning technology, and realizes the automatic generation of TCM prescriptions. Particularly, this paper considers the significance of referring to similar underlying prescriptions as herbal candidates in the TCM prescribing process. Moreover, this paper incorporates the idea of referring to the potential guidance information of corresponding prescriptions when model extracts symptoms representations. To provide a reference for inexperienced young TCM doctors when they prescribe, this paper proposes a dual-branch guidance strategy combined with candidate attention model (DGSCAM) to automatically generate TCM prescriptions based on symptoms text. The format of the data used this paper is the "symptoms-prescription" data pair. The specific method is as follows. First, DGSCAM realizes the extraction of key information of prescription-guided symptoms through a dual-branch network. Then, herbal candidates in the form of prescriptions that can treat symptoms are proposed in view of the compatibility knowledge of TCM prescriptions. To our knowledge, this is the first attempt to use prescriptions as herbal candidates in the prescription generation process. We conduct extensive experiments on a mixed public and clinical dataset, achieving 37.39% precision, 25.04% recall, and 29.99% F1 score, with an average doctor score of 7.7 out of 10. The experimental results show that our proposed model is valid and can generate more specialized TCM prescriptions than the baseline models. The DGSCAM developed by us has broad application scenarios and greatly promotes the research on intelligent TCM prescribing.

Icariin as an emerging candidate drug for anticancer treatment: Current status and perspective.

Icariin (ICA) is a kind of natural flavonoid compound monomer, which is derived from the extract of dried stems and leaves of Epimedium. Modern pharmacological studies have found that ICA has broad bioactive function in affecting the biological processes of a variety of cancers, including breast cancer, colorectal cancer, hepatocellular carcinoma, esophageal cancer and other cancers, which indicates that ICA has promising application value in the treatment of cancer patients in the future. Nevertheless, the targets and molecular mechanisms of ICA in cancer treatment have not been elucidated in detail. Therefore, in this review, we systematically summarizes the current research progress of ICA in a series of cancers. In particular, an emphasis is placed on the mechanism of ICA and its future development direction, aiming at providing relevant theoretical basis for the development and application of ICA in the future cancer treatment strategies.

A paraventricular thalamus to central amygdala neural circuit modulates acute stress-induced heightened wakefulness.

Heightened wakefulness in response to stressors is essential for survival but can also lead to sleep disorders like insomnia. The paraventricular thalamus (PVT) is both a critical thalamic area for wakefulness and a stress-sensitive brain region. However, whether the PVT and its neural circuitries are involved in controlling wakefulness in stress conditions remains unknown. Here, we find that PVT neurons projecting to the central amygdala (CeA) are activated by different stressors. These neurons are wakefulness-active and increase their activities upon sleep to wakefulness transitions. Optogenetic activation of the PVT-CeA circuit evokes transitions from sleep to wakefulness, whereas selectively silencing the activity of this circuit decreases time spent in wakefulness. Specifically, chemogenetic inhibition of CeA-projecting PVT neurons not only alleviates stress responses but also attenuates the acute stress-induced increase of wakefulness. Thus, our results demonstrate that the PVT-CeA circuit controls physiological wakefulness and modulates acute stress-induced heightened wakefulness.

Ursolic acid augments the chemosensitivity of drug-resistant breast cancer cells to doxorubicin by AMPK-mediated mitochondrial dysfunction.

Multidrug resistance remains the major obstacle to successful therapy for breast carcinoma. Ursolic acid (UA), a triterpenoid compound, has been regarded as a potential neoplasm chemopreventive drug in some preclinical studies since it exerts multiple biological activities. In this research, we investigated the role of UA in augmenting the chemosensitivity of drug-resistant breast carcinoma cells to doxorubicin (DOX), and we further explored the possible molecular mechanisms. Notably, we found that UA treatment led to inhibition of cellular proliferation and migration and cell cycle arrest in DOX-resistant breast cancers. Furthermore, combination treatment with UA and DOX showed a stronger inhibitory effect on cell viability, colony formation, and cell migration; induced more cell apoptosis in vitro; and generated a more potent inhibitory effect on the growth of the MCF-7/ADR xenograft tumor model than DOX alone. Mechanistically, UA effectively increased p-AMPK levels and concomitantly reduced p-mTOR and PGC-1α protein levels, resulting in impaired mitochondrial function, such as mitochondrial respiration inhibition, ATP depletion, and excessive reactive oxygen species (ROS) generation. In addition, UA induced a DNA damage response by increasing intracellular ROS production, thus causing cell cycle arrest at the G0/G1 phase. UA also suppressed aerobic glycolysis by prohibiting the expression and function of Glut1. Considered together, our data demonstrated that UA potentiated the susceptibility of DOX-resistant breast carcinoma cells to DOX by targeting energy metabolism through the AMPK/mTOR/PGC-1α signaling pathway, and it is a potential adjuvant chemotherapeutic candidate in MDR breast cancer.

Integrated serum pharmacochemistry and investigation of the anti-gastric ulcer effect of Zuojin pill in rats induced by ethanol.

CONTEXT: Zuojin Pill (ZJP) has been used to treat gastrointestinal problems in China for hundreds of years. OBJECTIVE: To discover more potential active ingredients and evaluate the gastroprotective mechanisms of ZJP. MATERIALS AND METHODS: An approach involving UPLC-Q-Orbitrap HRMS and serum pharmacochemistry was established to screen the multiple chemical constituents of ZJP. Male Sprague-Dawley (SD) rats were divided into six groups: normal control, ulcer control, omeprazole (30 mg/kg), and three ZJP groups (1.0, 2.0 and 4.0 g/kg). After oral treatment with ZJP or omeprazole for 7 days, all groups except the normal control group were orally administered 5 mL/kg ethanol to induce gastric ulceration. Histopathological assessment of gastric tissue was performed by haematoxylin and eosin staining. Antioxidant parameters and inflammatory mediators were determined using ELISA Kit and immunohistochemical analysis. RESULTS: Ninety components were identified in ZJP. Among them, 23 prototypes were found in rat serum after oral administration of ZJP. The ulcer inhibition was over 90.0% for all the ZJP groups. Compared with the ulcer control rats, ZJP (4.0 g/kg) enhanced the antioxidant capacity of gastric tissue: superoxide dismutase (1.33-fold), catalase (2.61-fold), glutathione (2.14-fold), and reduced the malondialdehyde level (0.48-fold). Simultaneously, the ZJP meaningfully lowered the content of tumour necrosis factor-α (0.76-fold), interleukin-6 (0.66-fold), myeloperoxidase (0.21-fold), and nuclear factor kappa B (p65) (0.62-fold). DISCUSSION AND CONCLUSIONS: This study showed ZJP could mitigate ethanol-induced rat gastric ulcers, which might benefit from the synergistic actions of multiple ingredients. The findings could support the quality control and clinical trials of ZJP.

Selenium-biofortified corn peptides: Attenuating concanavalin A-Induced liver injury and structure characterization.

The relationship between hepatoprotective effects of selenium-biofortified corn (Zea mays Linn) peptides (SeCPs) and its antioxidant ability was evaluated and the structure of SeCPs was identified. SeCPs and corn peptides (CPs) both had good antioxidant ability, and the effect of SeCPs was significantly higher than CPs within a certain concentration range (P < 0.05). Additionally, animal experiments indicated that SeCPs (200 mg/kg) had a significantly protective effect against concanavalin A (Con A) induced hepatic lesions, as it significantly declined glutamic-pyruvic transaminase (AST), alanine transaminase (ALT) activities, tumor necrosis factor alpha (TNF-α), interferon (IFN)-γ contents in serum, and malondialdehyde (MDA) contents in liver (P < 0.05). Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in liver were also significantly increased by SeCPs (P < 0.05). The amino acid composition of SeCPs with Mw < 1 kDa was mainly glutamic acid (Glu, 31.18%), leucine (Leu, 21.06%) and alanine (Ala, 13.26%). According to the retention time, the amino acid sequences of 8 selenium-biofortified corn peptides and 29 selenium-free corn peptides were identified. Our results illustrated that the mechanisms of SeCPs against Con A induced hepatic injury in mice may be related to its antioxidant ability and reduction of lipid peroxidation, inhibiting the release of immune factors, such as TNF-α and IFN-γ.

Genomic integration of ERRγ-HNF1ß regulates renal bioenergetics and prevents chronic kidney disease.

Mitochondrial dysfunction is increasingly recognized as a critical determinant of both hereditary and acquired kidney diseases. However, it remains poorly understood how mitochondrial metabolism is regulated to support normal kidney function and how its dysregulation contributes to kidney disease. Here, we show that the nuclear receptor estrogen-related receptor gamma (ERRγ) and hepatocyte nuclear factor 1 beta (HNF1ß) link renal mitochondrial and reabsorptive functions through coordinated epigenomic programs. ERRγ directly regulates mitochondrial metabolism but cooperatively controls renal reabsorption via convergent binding with HNF1ß. Deletion of ERRγ in renal epithelial cells (RECs), in which it is highly and specifically expressed, results in severe renal energetic and reabsorptive dysfunction and progressive renal failure that recapitulates phenotypes of animals and patients with HNF1ß loss-of-function gene mutations. Moreover, ERRγ expression positively correlates with renal function and is decreased in patients with chronic kidney disease (CKD). REC-ERRγ KO mice share highly overlapping renal transcriptional signatures with human patients with CKD. Together these findings reveal a role for ERRγ in directing independent and HNF1ß-integrated programs for energy production and use essential for normal renal function and the prevention of kidney disease.

Pharmacodynamic and pharmacokinetic assessment of pulmonary rehabilitation mixture for the treatment of pulmonary fibrosis.

Pulmonary rehabilitation mixture (PRM), a Chinese herbal medicine formula, has been used to treat pulmonary fibrosis for decades. In this study, we systematically evaluated the pharmacodynamic and pharmacokinetic performance of PRM. The pharmacodynamic results showed that PRM could improve the condition of CoCl2-stimulated human type II alveolar epithelial cells, human pulmonary microvascular endothelial cells, human lung fibroblasts and pulmonary fibrosis rats induced by bleomycin, PRM treatment reduced the expression of platelet-derived growth factor, fibroblast growth factor, toll-like receptor 4, high-mobility group box protein 1 and hypoxia-inducible factor 1α. In the pharmacokinetic study, an accurate and sensitive ultra-high performance liquid chromatography tandem mass spectrometry method was developed and validated for the simultaneous determination of calycosin, calycosin-7-O-glucoside, formononetin, ononin and mangiferin of PRM in the rat plasma for the first time. The method was then successfully applied to the comparative pharmacokinetic study of PRM in normal and pulmonary fibrosis rats. The five constituents could be absorbed in the blood after the oral administration of PRM and exhibited different pharmacokinetic behaviors in normal and pulmonary fibrosis rats. In summary, PRM exhibited a satisfactory pharmacodynamic and pharmacokinetic performance, which highlights PRM as a potential multi-target oral drug for the treatment of pulmonary fibrosis.

A comparative pharmacokinetic study of three flavonoids and three anthraquinones in normal and gastrointestinal motility disorders rat plasma after the oral administration of Wei-Chang-Shu tablet using high-performance liquid chromatography-tandem mass spectrometry.

A simple, fast and reliable high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification and pharmacokinetic study of three flavonoids (liquiritigenin, isoliquiritigenin and formononetin) and three anthraquinones (emodin, rhein and aloe-emodin), which are the bioactive ingredients of Wei-Chang-Shu tablet found in rat plasma. After extraction by liquid-liquid extraction with ethyl acetate, chromatographic separation was achieved on an Agilent Zorbax SB-C18 column (4.6 × 150 mm, 5 µm) at a flow rate of 1 mL/min by gradient elution using 0.1% aqueous acetic acid and acetonitrile. The detection was performed using a triple quadrupole mass spectrometer equipped with electrospray ionization source in the negative ionization and selected reaction monitoring mode. Method validation was performed in terms of specificity, carryover, linearity (r > 0.99), intra-/inter-day precision (1.0-10.1%), accuracy (relative error, <7.6%), stability (0.6-13.2%), extract recovery (74.9-91.9%) and matrix effect (89.1-109%). The lower limits of quantification of the six analytes varied from 0.92 to 10.4 ng/mL. The validated method was successfully applied to compare the pharmacokinetic properties of Wei-Chang-Shu tablet in normal rats and in rats with gastrointestinal motility disorders. The results indicated that there were obvious differences in the pharmacokinetic behavior between normal and model rats. This study will be helpful in the clinical application of Wei-Chang-Shu tablet.