The State-of-the-Art Antibacterial Activities of Glycyrrhizin: A Comprehensive Review.

Licorice (Glycyrrhiza glabra) is a plant of the genus Glycyrrhiza in the family Fabaceae/Leguminosae and is a renowned natural herb with a long history of medicinal use dating back to ancient times. Glycyrrhizin (GLY), the main active component of licorice, serves as a widely utilized therapeutic agent in clinical practice. GLY exhibits diverse medicinal properties, including anti-inflammatory, antibacterial, antiviral, antitumor, immunomodulatory, intestinal environment maintenance, and liver protection effects. However, current research primarily emphasizes GLY's antiviral activity, while providing limited insight into its antibacterial properties. GLY demonstrates a broad spectrum of antibacterial activity via inhibiting the growth of bacteria by targeting bacterial enzymes, impacting cell membrane formation, and altering membrane permeability. Moreover, GLY can also bolster host immunity by activating pertinent immune pathways, thereby enhancing pathogen clearance. This paper reviews GLY's inhibitory mechanisms against various pathogenic bacteria-induced pathological changes, its role as a high-mobility group box 1 inhibitor in immune regulation, and its efficacy in combating diseases caused by pathogenic bacteria. Furthermore, combining GLY with other antibiotics reduces the minimum inhibitory concentration, potentially aiding in the clinical development of combination therapies against drug-resistant bacteria. Sources of information were searched using PubMed, Web of Science, Science Direct, and GreenMedical for the keywords "licorice", "Glycyrrhizin", "antibacterial", "anti-inflammatory", "HMGB1", and combinations thereof, mainly from articles published from 1979 to 2024, with no language restrictions. Screening was carried out by one author and supplemented by others. Papers with experimental flaws in their experimental design and papers that did not meet expectations (antifungal papers, etc.) were excluded.

Clinical application and effect evaluation of acupoint thread embedding therapy and traditional Chinese medicine treatment based on menstrual cycle characteristics in the management of breast hyperplasia: An observational study.

To evaluate the effectiveness of the combination of acupoint embedding therapy and traditional Chinese medicine dialectical treatment regimen in improving clinical symptoms, promoting tumor regression, controlling adverse reactions and complications, and enhancing patient satisfaction by comparing and analyzing the clinical data of 120 breast tumor patients. One hundred twenty patients with breast cancer were divided into a treatment group (60 cases) and a control group (60 cases) according to different treatment plans. Patients in the treatment group received a combination of acupoint embedding therapy and traditional Chinese medicine dialectical treatment based on different time points of the menstrual cycle. Including the proportion of reduction in the number of breast masses, the proportion of reduction in mass size, changes in pain severity scores, tumor regression rate, regression time, incidence of adverse reactions and complications, and patient satisfaction. Statistical software was used to analyze the data to evaluate differences between the 2 groups. In terms of clinical symptoms, the proportion of reduction in the number of breast masses in the treatment group averaged 50%, significantly higher than the 25% in the control group; the proportion of reduction in mass size averaged 40%, also higher than the 15% in the control group; and the improvement in pain severity scores was also superior to the control group. Regarding tumor regression, the tumor regression rate in the treatment group reached 85%, with an average regression time of 6.2 weeks, both significantly better than the 55% and 9.8 weeks in the control group. In terms of adverse reactions and complications, the incidence rate in the treatment group was relatively low, and no serious adverse events occurred. Patient satisfaction surveys showed that the treatment group had significantly higher satisfaction with treatment effectiveness, treatment process, and physician service attitude compared to the control group. Based on clinical data from 120 breast tumor patients, the results of this study indicate that breast tumor patients treated with a specific treatment regimen have significant advantages in improving clinical symptoms, tumor regression, controlling adverse reactions and complications, and patient satisfaction. This treatment regimen has high clinical application value and deserves further promotion.

Lysine-specific demethylase 7A (KDM7A): A potential target for disease therapy.

Histone demethylation is a kind of epigenetic modification mediated by a variety of enzymes and participates in regulating multiple physiological and pathological events. Lysine-specific demethylase 7A is a kind of α-ketoglutarate- and Fe(II)-dependent demethylase belonging to the PHF2/8 subfamily of the JmjC demethylases. KDM7A is mainly localized in the nucleus and contributes to transcriptional activation via removing mono- and di-methyl groups from the lysine residues 9 and 27 of Histone H3. Mounting studies support that KDM7A is not only necessary for normal embryonic, neural, and skeletal development, but also associated with cancer, inflammation, osteoporosis, and other diseases. Herein, the structure of KDM7A is described by comparing the similarities and differences of its amino acid sequences of KDM7A and other Histone demethylases; the functions of KDM7A in homeostasis and dyshomeostasis are summarized via documenting its content and related signaling; the currently known KDM7A-specific inhibitors and their structural relationship are listed based on their structure optimization and pharmacological activities; and the challenges and opportunities in exploring functions and developing targeted agents of KDM7A are also prospected via presenting encountered problems and potential solutions, which will provide an insight in functional exploration and drug discovery for KDM7A-related diseases.

The emerging roles of leukocyte cell-derived chemotaxin-2 in immune diseases: From mechanisms to therapeutic potential.

Leukocyte cell-derived chemotaxin-2 (LECT2, also named ChM-II), initially identified as a chemokine mediating neutrophil migration, is a multifunctional secreted factor involved in diverse physiological and pathological processes. The high sequence similarity of LECT2 among different vertebrates makes it possible to explore its functions by using comparative biology. LECT2 is associated with many immune processes and immune-related diseases via its binding to cell surface receptors such as CD209a, Tie1, and Met in various cell types. In addition, the misfolding LECT2 leads to the amyloidosis of several crucial tissues (kidney, liver, and lung, etc.) by inducing the formation of insoluble fibrils. However, the mechanisms of LECT2-mediated diverse immune pathogenic conditions in various tissues remain to be fully elucidated due to the functional and signaling heterogeneity. Here, we provide a comprehensive summary of the structure, the "double-edged sword" function, and the extensive signaling pathways of LECT2 in immune diseases, as well as the potential applications of LECT2 in therapeutic interventions in preclinical or clinical trials. This review provides an integrated perspective on the current understanding of how LECT2 is associated with immune diseases, with the aim of facilitating the development of drugs or probes against LECT2 for the theranostics of immune-related diseases.

The role of lysine-specific demethylase 6A (KDM6A) in tumorigenesis and its therapeutic potentials in cancer therapy.

Histone demethylation is a key post-translational modification of chromatin, and its dysregulation affects a wide array of nuclear activities including the maintenance of genome integrity, transcriptional regulation, and epigenetic inheritance. Lysine specific demethylase 6A (KDM6A, also known as UTX) is an Fe2+- and α-ketoglutarate- dependent oxidase which belongs to KDM6 Jumonji histone demethylase subfamily, and it can remove mono-, di- and tri-methyl groups from methylated lysine 27 of histone H3 (H3K27me1/2/3). Mounting studies indicate that KDM6A is responsible for driving multiple human diseases, particularly cancers and pharmacological inhibition of KDM6A is an effective strategy to treat varieties of KDM6A-amplified cancers in cellulo and in vivo. Although there are several reviews on the roles of KDM6 subfamily in cancer development and therapy, all of them only simply introduce the roles of KDM6A in cancer without systematically summarizing the specific mechanisms of KDM6A in tumorigenesis, which greatly limits the advances on the understanding of roles KDM6A in varieties of cancers, discovering targeting selective KDM6A inhibitors, and exploring the adaptive profiles of KDM6A antagonists. Herein, we present the structure and functions of KDM6A, simply outline the functions of KDM6A in homeostasis and non-cancer diseases, summarize the role of KDM6A and its distinct target genes/ligand proteins in development of varieties of cancers, systematically classify KDM6A inhibitors, sum up the difficulties encountered in the research of KDM6A and the discovery of related drugs, and provide the corresponding solutions, which will contribute to understanding the roles of KDM6A in carcinogenesis and advancing the progression of KDM6A as a drug target in cancer therapy.

A state-of-the-art review on LSD1 and its inhibitors in breast cancer: Molecular mechanisms and therapeutic significance.

Breast cancer (BC) is a kind of malignant cancer in women, and it has become the most diagnosed cancer worldwide since 2020. Histone methylation is a common biological epigenetic modification mediating varieties of physiological and pathological processes. Lysine-specific demethylase 1 (LSD1), a first identified histone demethylase, mediates the removal of methyl groups from histones H3K4me1/2 and H3K9me1/2 and plays a crucial role in varieties of cancer progression. It is also specifically amplified in breast cancer and contributes to BC tumorigenesis and drug resistance via both demethylase and non-demethylase manners. This review will provide insight into the overview structure of LSD1, summarize its action mechanisms in BC, describe the therapeutic potential of LSD1 inhibitors in BC, and prospect the current opportunities and challenges of targeting LSD1 for BC therapy.

Targeting PGAM1 in cancer: An emerging therapeutic opportunity.

Glycolysis is a preferred metabolic pattern of cancer cells. Phosphoglycerate mutase 1 (PGAM1) is a pivotal glycolytic enzyme that catalyzes the reciprocal conversion between 2-phosphoglycerate and 3-phosphoglycerate. It also stimulates anabolic pathways, generates adenosine triphosphate, and keeps redox balance under hypoxic conditions. Mounting evidence supports that PGAM1 is overexpressed in many cancers and promotes their progression. The critical roles of PGAM1 in tumorigenesis make it a promising theranostical target for cancer. The aberrant expression of PGAM1 enables it to become a potential diagnosis gene for several cancers, and its heterogeneous regulations via interacting with its different ligands increase the possibility of it as a target for cancer therapy and discovery of tens of PGAM1 inhibitors, which can provide the potential feasibility for cancer treatment. This review provides insights into structure, function, and regulation of PGAM1, summarizes its mechanism in tumorigenesis, reviews the advanced status of PGAM1 inhibitors in cancer diagnosis and treatment, and finally emphasizes PGAM1 as an appealing theranostical target for cancer.

Berberine as a potential agent for breast cancer therapy.

Breast cancer (BC) is a common malignancy that mainly occurred in women and it has become the most diagnosed cancer annually since 2020. Berberine (BBR), an alkaloid extracted from the Berberidacea family, has been found with broad pharmacological bioactivities including anti-inflammatory, anti-diabetic, anti-hypertensive, anti-obesity, antidepressant, and anticancer effects. Mounting evidence shows that BBR is a safe and effective agent with good anticancer activity against BC. However, its detailed underlying mechanism in BC treatment remains unclear. Here, we will provide the evidence for BBR in BC therapy and summarize its potential mechanisms. This review briefly introduces the source, metabolism, and biological function of BBR and emphasizes the therapeutic effects of BBR against BC via directly interacting with effector proteins, transcriptional regulatory elements, miRNA, and several BBR-mediated signaling pathways. Moreover, the novel BBR-based therapeutic strategies against BC improve biocompatibility and water solubility, and the efficacies of BBR are also briefly discussed. Finally, the status of BBR in BC treatment and future research directions is also prospected.

Upregulation of miR-33 Exacerbates Heat-Stress-Induced Apoptosis in Granulosa Cell and Follicular Atresia of Nile Tilapia (Oreochromis niloticus) by Targeting TGFß1I1.

High temperature affects egg quality and increases follicular atresia in teleosts. The present study aimed to explore the regulated mechanism of ovary syndrome of Nile tilapia (Oreochromis niloticus) exposed to heat stress. To this end, we conducted histological and biochemical analyses and integrated miRNA-target gene analyses. The histochemical analyses confirmed that heat stress promoted the apoptosis of granulosa cell and therefore resulted in increased follicular atresia in the ovary. Heat stress led to the differential expression of multiple miRNAs (miR-27e, -27b-3p, -33, -34a -133a-5p, and -301b-5p). In a luciferase activity assay, miR-33 bound to the 3'-untranslated region (UTR) of the TGFß1I1 (transforming growth factor-ß1-induced transcript 1) gene and inhibited its expression. A TGFß1I1 gene signal was detected in the granulosa cells of Nile tilapia by immunohistochemical analysis. Up-regulation of the miR-33 of tilapia at 6 d and 12 d exposed to heat (34.5 °C ± 0.5 °C) had significant down-regulation of the TGFß1I1 expression of the gene and protein in tilapia ovaries. An miRNA-target gene integrated analysis revealed that miR-33 and TGFß1I1 function in an apoptosis-related signal pathway. The signal transduction of the vascular endothelial growth factor (VEGF) family members VEGFA and its receptor (KDR) in the heat-stressed group decreased significantly compared with the control group. Transcript-levels of the Bax and Caspase-3 as apoptotic promotors were activated and Bcl-2 and Caspase-8 as apoptotic inhibitors were suppressed in the heat-stressed tilapia. These results suggest that heat stress increases the expression of miR-33, which targets TGFß1I1 and inhibits its expression, resulting in decreased levels of follicle-stimulating hormone and 17ß-estradiol and increased apoptosis by suppressing VEGF signaling, eventually inducing follicular atresia. In conclusion, our results show that the miR-33/TGFß1I1 axis of Nile tilapia is involved in the follicular development of broodstock, and can suppress VEGF signaling to accelerate follicular atresia. Our findings demonstrate the suppressive role of miR-33 during oocyte development in Nile tilapia.

Ultrasound-guided suprainguinal fascia iliaca block combined with a sacral plexus block for lower extremity surgery: A case report.

RATIONALE: The anesthetic management of patients with severe pulmonary hypertension is different from that of normal, healthy patients, and regional nerve blocks are commonly used for them. Due to the individual variability of the course, distribution, and branching of the nerves below the inguinal ligament, the supra-inguinal fascia iliaca (SIFI) block has a wider and more stable blocking area. In combination with the sacral plexus block, they can satisfy the needs of surgical anesthesia below the hip. PATIENT CONCERNS: A 46-year-old man with tuberculosis, chronic obstructive pulmonary disease, pulmonary heart disease, World Health Organization (WHO) class III pulmonary hypertension and right heart dysfunction, and American Society of Anesthesiologists physical status class III needed fixation of an intramedullary nail in the left lower extremity. Additionally, he had broken his left lower limb after a recent fall. Both general anesthesia and epidural anesthesia were not appropriate. DIAGNOSES: The patient had a clear history of tuberculosis, computerized tomography scan displayed destructive pneumonophthisis. Furthermore, he had chronic obstructive pulmonary disease and pulmonary heart disease. INTERVENTIONS: An ultrasound-guided SIFI combined with a sacral plexus block was successfully performed for surgical anesthesia and avoided all hemodynamic fluctuations. OUTCOMES: We successfully performed an ultrasound-guided SIFI combined with a sacral plexus block for surgical anesthesia and avoided all hemodynamic fluctuations. LESSONS: Ultrasound-guided suprainguinal fascia iliaca block combined with a sacral plexus block can be suitable for anesthesia for patients with severe circulatory compromise.

Combined neurolytic block of celiac and superior hypogastric plexuses for incapacitating upper abdominal cancer pain.

PURPOSE: To evaluate the efficacy of a combined neurolytic block of the celiac and superior hypogastric plexuses for incapacitating upper abdominal cancer pain. METHODS: Fifty-two patients with advanced upper abdominal malignancies and incapacitating pain were equally randomized to receive a combined neurolytic block of the celiac and superior hypogastric plexuses (combined group) or a neurolytic celiac plexus block alone (NCPB group) using a 90% ethanol trans-intervertebral disk approach under CT guidance. Visual analogue scores (VAS), morphine consumption, and quality of life (QoL) were assessed before the procedure and 24 hrs, 1 week, 1 month, and 3 months after the procedure. The complications and side effects were also recorded. RESULTS: The amount of ethanol used was 30 ± 5 ml in the combined group and 21 ± 3 ml in the NCPB group. VAS scores and morphine consumption decreased significantly pre- compared to post-procedure in both groups (p<0.05). QoL significantly improved 24 hrs, 1 week, and 1 month after the procedure compared with each group pre-procedure (p<0.05), but not after 3 months (p>0.05). The combined group had significantly lower VAS and morphine consumption than the NCPB group (p<0.05). QoL scores were significantly higher in the combined group 24 hrs, 1 week, and 1 month post-procedure than the NCPB group (p<0.05), but not after 3 months (p>0.05). CONCLUSION: A combined neurolytic block of the celiac and superior hypogastric plexuses is more effective than neurolytic celiac plexus block alone in pain relief for patients with advanced upper abdominal cancer.

Effect of qubi zhentong recipe on synovial gene expression in collagen-induced arthritis in rats.

OBJECTIVE: To investigate the effect of the Chinese medical formula Qubi Zhentong Recipe(, QZR) on the synovial gene expression profile in collagen-induced arthritis (CIA) rats. METHODS: Ten rats were randomly chosen from 60 rats as the control group, and the other 50 rats were used for the CIA models. The CIA model group was constructed by bovine injection of type II collagen through the rats' neck and tail. Twenty rats were randomly chosen from 34 successful CIA models and randomly assigned into two groups: the model group (n =10) and the QZR group (n=10). The QZR group was fed intragastrically with QZR 22.9 g/(kg·d) (10 times the clinical adult dose), and the CIA model group was given the same dose of normal saline. Both model and QZR groups were administered treatment once a day. Total RNA was collected from the knee joint synovium after 30 days. The change in gene expression profile was analyzed by a whole gene chip. RESULTS: A total of 76 genes showed a difference in expression between CIA model group and the control group; 35 genes were down-regulated and 41 were up-regulated. A total of 67 genes showed a difference in expression between the model group and the QZR group; 48 genes were down-regulated and 19 were upregulated. CONCLUSIONS: QZR may affect CIA by stimulating multiple genes and targets, which are related to oncogenes, apoptosis, metabolism, the immune system, ion channels, and transport proteins.

[Effects of qubi zhentong recipe on the expressions of IL-1beta, IL-8, and VEGF in the synovial of rats with collagen-inducing arthritis].

OBJECTIVE: To research the effects of Qubi Zhentong Recipe (QZR) on the expressions of interleukin-1beta (IL-1beta), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) in the synovial of rats with collagen-inducing arthritis (CIA), and to discuss its mechanisms of action. METHODS: Healthy male Wistar rats were recruited and randomly divided into the model group ( n = 50) and the normal control group (n = 10). Rats of the model group were injected with type II collagen of bovine (BC II) emulsion in the tail and nape to establish the CIA model. After successful modeling, 30 successfully modeled rats were selected and randomly divided into three groups, i.e., the model group (n = 10), the QZR group (n = 10), and the methotrexate (MTX) group (n = 10). Rats in the normal control group and the model group were administered with physiological saline by gastrogavage, while those in the QZR group were administered with QZR at 22.9 g/kg by gastrogavage. All medication was performed once daily. The rats in the MTX group were administered with MTX suspension at 0.78 mg/kg by gastrogavage, once per week. After 30-day treatment, the levels of IL-1beta, IL-8, and VEGF in the synovial were detected by immunohistochemical method. The arthritis index (AI) was scored before and after medication. RESULTS: After treatment the AL score of the QZR group and the MTX group was obviously lower than that of the model group (P < 0.01). The AI score of the two drug groups were lower than that before treatment (P < 0.01). Compared with the normal control group, the expression levels of IL-1beta, IL-8, and VEGF obviously increased in the model group (P < 0.01). Compared with the model group, the expression levels of IL-1beta, IL-8, and VEGF were significantly lower in the two drug groups (P < 0.01). But there was no statistical difference between the QZR group and the MTX group (P > 0.05). CONCLUSION: Decreasing the expression levels of IL-1beta, IL-8, and VEGF in the synovial of CIA rats may be one of the mechanisms for treating CIA by QZR.

[Observation on the analgesic effect of transcutaneous electrical acupoint stimulation for breast radical carcinoma operation].

OBJECTIVE: To observe the analgesic effect of transcutaneous electrical acupoint stimulation (TEAS) in assisting general anesthesia (GA) for radical operation of breast carcinoma so as to explore its clinical application value. METHODS: Sixty patients scheduled for radical operations of the breast carcinoma were randomly and equally divided into GA group and TEAS+ GA group. For GA, Propofol [4.5 microg/mL, target concentration; (3.0 +/- 0.5) microg/mL during operation] was used in combination with Sufentanil (0.25 microg/kg) and Cis-atracurium amine (0.2 mg/kg). TEAS (5-10 mA, 2 Hz/100 Hz) was applied to Hegu (LI 4)-Laogong (PC 8) and Neiguan (PC 6)-Waiguan (SJ 5) on the affected side of the body for 30 min. Heart rate (HR), mean aterial pressure (MAP), tube removing time and postoperative complications were recorded. Plasma beta-endorphin content was assayed by radioimmunoassay. RESULTS: After anesthesia, patients with reduction in MAP in GA group were significantly more than those in TEAS+GA group (P < 0.05), and their HR decreased remarkably (P < 0.05). After tracheal intubation, MAP in TEAS+GA group kept relatively stable, which was superior to that of GA group (P < 0.05). In comparison with GA group, the patients' analepsia time and tube withdrawal time of TEAS+ GA group were significantly shorter; and the dosage of analgesics of TEAS+GA group was significantly smaller than that of GA group (P < 0.05). Patients with complications of pain, restlessness, drowsiness, nausea and vomitting were obviously fewer in TEAS + GA group than those in GA group. Compared with GA group, plasma beta-endorphin content in TEAS+GA group increased considerably 30 min after TEAS, 5 min after skin-incision and after operation (P < 0.05). CONCLUSION: TEAS combined with general anesthesia for breast radical carcinoma operation can help keep a stable blood pressure during surgery, reduce the dosage of analgesics and strengthen pain relief. The analgesic effect of TEAS may be related to its effect in up-regulating plasma beta-endorphin level.