Gallic Acid Restores the Sulfonamide Sensitivity of Multidrug-Resistant Streptococcus suis via Polypharmaceology Mechanism.

Due to the large amount of antibiotics used for human therapy, agriculture, and even aquaculture, the emergence of multidrug-resistant Streptococcus suis (S. suis) led to serious public health threats. Antibiotic-assisted strategies have emerged as a promising approach to alleviate this crisis. Here, the polyphenolic compound gallic acid was found to enhance sulfonamides against multidrug-resistant S. suis. Mechanistic analysis revealed that gallic acid effectively disrupts the integrity and function of the cytoplasmic membrane by dissipating the proton motive force of bacteria. Moreover, we found that gallic acid regulates the expression of dihydrofolate reductase, which in turn inhibits tetrahydrofolate synthesis. As a result of polypharmacology, gallic acid can fully restore sulfadiazine sodium activity in the animal infection model without any drug resistances. Our findings provide an insightful view into the threats of antibiotic resistance. It could become a promising strategy to resolve this crisis.

Sustainable extraction of ligustilide and ferulic acid from Angelicae Sinensis Radix, for antioxidant and anti-inflammatory activities.

The 2030 Agenda for Sustainable Development envisions a rational use of energy and resources in all technological processes. However, in the extraction methods of compounds from medicinal plants and herbs, there is an urgent to reduce the use of organic solvents and increase the energy efficiency of these methods. Therefore, a sustainable extraction method (enzyme and ultrasonic co-assisted aqueous two-phase extraction, EUA-ATPE) of simultaneous extraction and separation of ferulic acid and ligustilide from Angelicae Sinensis Radix (ASR) was developed by integrating enzyme-assisted extraction (EAE) with ultrasonic-assisted aqueous two-phase extraction (UAE- ATPE). The effects of different enzymes, extraction temperature, pH, ultrasonic time, liquid-to-materials ratio, etc., were optimized by single-factor experiments and central composite design (CCD). Under the optimum conditions, the highest comprehensive evaluation value (CEV) and extraction yield were obtained by EUA-ATPE. Furthermore, recovery (R), partition coefficient (K), and scanning electron microscopy (SEM) analysis revealed that enzyme and ultrasonic treatment improved mass transfer diffusion and increased the degree of cell disruption. Besides, the EUA-ATPE extracts have shown great antioxidant and anti-inflammatory activity in vitro. Finally, compared to different extraction methods, EUA-ATPE achieved higher extraction efficiency and higher energy efficiency due to the synergistic effect between EAE and UAE-ATPE. Therefore, the EUA-ATPE provides a sustainable method for extracting bioactive compounds from medicinal plants and herbs, contributing to Sustainable Development Goals (SDG), including SDG-6, SDG-7, SDG-9, SDG-12, and SDG-15.

Polypharmacology-based approach for screening TCM against coinfection of Mycoplasma gallisepticum and Escherichia coli.

Natural products and their unique polypharmacology offer significant advantages for finding novel therapeutics particularly for the treatment of complex diseases. Meanwhile, Traditional Chinese Medicine exerts overall clinical benefits through a multi-component and multi-target approach. In this study, we used the previously established co-infection model of Mycoplasma gallisepticum and Escherichia coli as a representative of complex diseases. A new combination consisting of 6 herbs were obtained by using network pharmacology combined with transcriptomic analysis to reverse screen TCMs from the Chinese medicine database, containing Isatdis Radix, Forsythia Fructus, Ginkgo Folium, Mori Cortex, Licorice, and Radix Salviae. The results of therapeutic trials showed that the Chinese herbal compounds screened by the target network played a good therapeutic effect in the case of co-infection. In summary, these data suggested a new method to validate target combinations of natural products that can be used to optimize their multiple structure-activity relationships to obtain drug-like natural product derivatives.

Effects of auricular acupuncture stimulation on healthy adults' upper limb motor-evoked potentials: A randomized, crossover, double-blind study.

Objective: The aim of this study was to determine whether auricular acupuncture has neuromodulatory effects on the motor cortex of healthy adults. Methods: Fourteen healthy subjects received a real auricular acupuncture stimulation (SF1) session and a sham acupuncture stimulation session. The interval between the two types of stimulation was more than 24 h. A finger dexterity test (taping score and taping speed by using ipad) was assessed, and motor-evoked potentials (MEP) were assessed before and after each stimulation. Results: Before the treatment, there were no significant differences in MEP amplitude, tapping score, or tapping speed (P > 0.05) between the real and sham stimulation conditions. After the treatment, the MEP amplitude, tapping score, and tapping speed in the real stimulation condition increased significantly compared to the pre-stimulation measurements and were significantly higher than those in the sham stimulation condition (P < 0.01). In the sham stimulation condition, the MEP amplitude, tapping score, and tapping speed decreased significantly compared to the pre-stimulation measurements (P < 0.05). Conclusion: Acupuncture of auricular points can modulate the excitability of the motor cortex area of controlling the upper limbs. Clinical trial registration: [http://www.chictr.org.cn/index.aspx], identifier [ChiCTR2100051608].

A near-infrared light-excitable immunomodulating nano-photosensitizer for effective photoimmunotherapy.

Photodynamic therapy has great potential for tumor ablation and the activation of antitumor immune responses. However, its overall therapeutic efficiency is often limited by the immunosuppressive tumor microenvironment. We developed a near-infrared light-excitable immunomodulating nano-photosensitizer (NeINP) that can improve reactive oxygen species production and regulate the immunosuppressive TME to improve photoimmunotherapy. The NeINP is composed of a photosensitive core and a pH-responsive polymer shell, which allows for NeINP loading and delivery of small-molecular immunomodulators to tumor sites for regulation of the immunosuppressive TME and effective photoimmunotherapy. Through the co-delivery of celecoxib and the NIR-triggered photodynamic core to tumors, the NeINP was shown to regulate the immunosuppressive TME and enhance antitumor immunity, leading to the elimination of residual tumor and reduction of metastasis and recurrence. The NeINP can be optimized to co-deliver other immunomodulators, and thus has potential as a universal platform for efficient, precise photoimmunotherapy.