Cucurbitacin B attenuates osteoarthritis development by inhibiting NLRP3 inflammasome activation and pyroptosis through activating Nrf2/HO-1 pathway.

Osteoarthritis (OA) is a complicated joint disorder characterized by inflammation that causes joint destruction. Cucurbitacin B (CuB) is a naturally occurring triterpenoid compound derived from plants in the Cucurbitaceae family. The aim of this study is to investigate the potential role and mechanisms of CuB in a mouse model of OA. This study identified the key targets and potential pathways of CuB through network pharmacology analysis. In vivo and in vitro studies confirmed the potential mechanisms of CuB in OA. Through network pharmacology, 54 potential targets for CuB in treating OA were identified. The therapeutic potential of CuB is associated with the nod-like receptor pyrin domain 3 (NLRP3) inflammasome and pyroptosis. Molecular docking results indicate a strong binding affinity of CuB to nuclear factor erythroid 2-related factor 2 (Nrf2) and p65. In vitro experiments demonstrate that CuB effectively inhibits the expression of pro-inflammatory factors induced by interleukin-1ß (IL-1ß), including cyclooxygenase-2, inducible nitric oxide synthase, IL-1ß, and IL-18. CuB inhibits the degradation of type II collagen and aggrecan in the extracellular matrix (ECM), as well as the expression of matrix metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin motifs-5. CuB protects cells by activating the Nrf2/hemeoxygenase-1 (HO-1) pathway and inhibiting nuclear factor-κB (NF-κB)/NLRP3 inflammasome-mediated pyroptosis. Moreover, in vivo experiments show that CuB can slow down cartilage degradation in an OA mouse model. CuB effectively prevents the progression of OA by inhibiting inflammation in chondrocytes and ECM degradation. This action is further mediated through the activation of the Nrf2/HO-1 pathway to inhibit NF-κB/NLRP3 inflammasome activation. Thus, CuB is a potential therapeutic agent for OA.

[Baicalin induces ferroptosis in HepG2 cells by inhibiting ROS-mediated PI3K/Akt/FoxO3a signaling pathway].

This study aims to investigate whether baicalin induces ferroptosis in HepG2 cells and decipher the underlying mechanisms based on network pharmacology and cell experiments. HepG2 cells were cultured in vitro and the cell viability was detected by the cell counting kit-8(CCK-8). The transcriptome data of hepatocellular carcinoma were obtained from the Cancer Genome Atlas(TCGA), and the ferroptosis gene data from FerrDb V2. The DEG2 package was used to screen the differentially expressed genes(DEGs), and the common genes between DEGs and ferroptosis genes were selected as the target genes that mediate ferroptosis to regulate hepatocellular carcinoma progression. The functions and structures of the target genes were analyzed by Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment with the thresholds of P<0.05 and |log_2(fold change)|>0.5. DCFH-DA probe was used to detect the changes in the levels of cellular reactive oxygen species(ROS) in each group. The reduced glutathione(GSH) assay kit was used to measure the cellular GSH level, and Fe~(2+) assay kit to determine the Fe~(2+) level. Real-time quantitative PCR(RT-PCR) was employed to measure the mRNA levels of glutathione peroxidase 4(GPX4) and solute carrier family 7 member 11(SLC7A11) in each group. Western blot was employed to determine the protein levels of GPX4, SLC7A11, phosphatidylinositol 3-kinase(PI3K), p-PI3K, protein kinase B(Akt), p-Akt, forkhead box protein O3a(FoxO3a), and p-FoxO3a in each group. The results showed that treatment with 200 µmol·L~(-1) baicalin for 48 h significantly inhibited the viability of HepG2 cells. Ferroptosis in hepatocellular carcinoma could be regulated via the PI3K/Akt signaling pathway. The cell experiments showed that baicalin down-regulated the expression of SLC7A11 and GPX4, lowered the GSH level, and increased ROS accumulation and Fe~(2+) production in HepG2 cells. However, ferrostatin-1, an ferroptosis inhibitor, reduced baicalin-induced ROS accumulation, up-regulated the expression of SLC7A11 and GPX4, elevated the GSH level, and decreased PI3K, Akt, and FoxO3a phosphorylation. In summary, baicalin can induce ferroptosis in HepG2 cells by inhibiting the ROS-mediated PI3K/Akt/FoxO3a pathway.

[Comparison on biological activities of Lycium barbarum polysaccharides extracted with five methods].

Studying the physicochemical properties and biological activities of Lycium barbarum polysaccharides(LBPs) is of great significance. The previous study had extracted LBPs(LBP-1, LBP-2, LBP-3, LBP-4, and LBP-5) by five different methods(cold water extraction, boiling water reflux extraction of the residue after cold water extraction, ultrasonic extraction with 50% ethanol, ultrasonic extraction with 25% ethanol of the residue after 50% ethanol extraction, and hot water extraction). In this study, the structures of the obtained five LBPs were characterized by UV spectroscopy, thermogravimetric analysis, and scanning electron microscopy. Furthermore, the antioxidant, blood lipid-lowering, nitrosation-inhibting, acetylcholinesterase-inhibiting, and tyrosinase-inhibiting activities of the five LBPs were measured in vitro. The results showed that high-temperature extraction destroyed the polysaccharide structure, while ultrasound-assisted extraction ensured the structural integrity. The thermal stability and degradation behaviors differed among the five LBPs. However, the UV spectroscopic results of the five LBPs did not show significant differences, and all of the five LBPs showed the characteristic absorption peaks of proteins. LBP-3 and LBP-4 exhibited strong antioxidant activity, while LBP-3 had the strongest blood lipid-lowering activity. In addition, LBP-3 outperformed other LBPs in inhibiting nitrosation and acetylcholineste-rase, and LBP-2 showed the strongest inhibitory effect on tyrosinase. This study explored the effects of different extraction methods on the physicochemical properties and biological activities of LBPs, with a view to providing a basis for the selection of suitable extraction methods to obtain LBPs with ideal biological activities.

Neurite orientation dispersion and density imaging quantifies microstructural impairment in the thalamus and its connectivity in amyotrophic lateral sclerosis.

AIMS: To evaluate microstructural impairment in the thalamus and thalamocortical connectivity using neurite orientation dispersion and density imaging (NODDI) in amyotrophic lateral sclerosis (ALS). METHODS: This study included 47 healthy controls and 43 ALS patients, whose structural and diffusion-weighted data were collected. We used state-of-the-art parallel transport tractography to identify thalamocortical pathways in individual spaces. Thalamus was then parcellated into six subregions based on its connectivity pattern with the priori defined cortical (i.e., prefrontal/motor/somatosensory/temporal/posterior-parietal/occipital) regions. For each of the thalamic and cortical subregions and thalamo-cortical tracts, we compared the following NODDI metrics between groups: orientation dispersion index (ODI), neurite density index (NDI), and isotropic volume fraction (ISO). We also used these metrics to conduct receiver operating characteristic curve (ROC) analyses and Spearman correlation. RESULTS: In ALS patients, we found decreased ODI and increased ISO in the thalamic subregion connecting the left motor cortex and other extramotor (e.g., somatosensory and occipital) cortex (Bonferroni-corrected p < 0.05). NDI decreased in the bilateral thalamo-motor and thalamo-somatosensory tracts and in the right thalamo-posterior-parietal and thalamo-occipital tracts (Bonferroni-corrected p < 0.05). NDI reduction in the bilateral thalamo-motor tract (p = 0.017 and 0.009) and left thalamo-somatosensory tract (p = 0.029) was correlated with disease severity. In thalamo-cortical tracts, NDI yielded a higher effect size during between-group comparisons and a greater area under ROC (p < 0.05) compared with conventional diffusion tensor imaging metrics. CONCLUSIONS: Microstructural impairment in the thalamus and thalamocortical connectivity is the hallmark of ALS. NODDI improved the detection of disrupted thalamo-cortical connectivity in ALS.

Study on the effects and mechanisms of Wenzhong Bushen Formula in improving ovarian reserve decline in mice based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: The Wenzhong Bushen Formula (WZBSF) is a traditional Chinese medicine empirical formula known for its effects in tonifying qi, strengthening the spleen, warming the kidneys, promoting yang, regulating blood circulation, and balancing menstruation. Clinical evidence has demonstrated its significant efficacy in treating Diminished Ovarian Reserve (DOR) by improving ovarian reserves. However, the specific pharmacological mechanisms of WZBSF remain unclear. AIM OF THE STUDY: This study aims to investigate the mechanisms by which WZBSF improves ovarian reserve decline through network pharmacology and animal experiments. METHODS AND MATERIALS: WZBSF was analyzed using a dual UPLC-MS/MS and GC-MS platform. Effective components and targets of WZBSF were obtained from the TCMSP database and standardized using UniProt. Disease targets were collected from GeneCard, OMIM, PHARMGKB, and DisGeNET databases, with cross-referencing between the two sets of targets. A PPI protein interaction network was constructed using Cytoscape3.9.1 and STRING database, followed by KEGG and GO enrichment analysis using the Metascape database. Finally, an ovarian reserve decline model was established in mice, different doses of WZBSF were administered, and experimental validation was conducted through serum hormone detection, H&E staining, immunofluorescence (IF), immunohistochemistry (IHC), and Western blot analysis (WB). RESULTS: WZBSF shares 145 common targets with ovarian reserve decline. GO enrichment analysis revealed involvement in biological processes such as response to hormone stimulation and phosphatase binding, while KEGG analysis implicated pathways including the PI3K-AKT signaling pathway and FoxO signaling pathway. In mice with ovarian reserve decline, WZBSF restored weight gain rate, increased ovarian index, normalized estrous cycles, reversed serum hormone imbalances, restored various follicle counts, and improved ovarian morphology. Additionally, WZBSF reduced p-AKT and p-FOXO3a levels, preventing excessive activation of primordial follicles and maintaining ovarian reserve. CONCLUSION: WZBSF can ameliorate cyclophosphamide and busulfan-induced ovarian reserve decline, and its mechanism may be associated with the inhibition of the PI3K/AKT/FOXO3a signaling pathway.

Painless and non-invasive treatment of plantar warts utilizing traditional Chinese medicine soaking: A case report.

BACKGROUND: Warts result from an infection with the human papilloma virus (HPV). Plantar warts, also known as Verruca plantaris, can be notably painful for the patient and possess contagious qualities, thus necessitating assertive treatment. Despite several available approaches for addressing plantar warts, efficacy remains elusive. CASE PRESENTATION: One 22-year-old firefighter suffered from numerous plantar warts. After 26 days of traditional Chinese medicine soaking, the rashes completely disappeared. The treatment was without complications or discomfort, and a three-month follow-up showed no recurrence. CONCLUSION: Our case investigation highlighted the efficacy of herbal soaking as a safe, painless, and non-invasive therapeutic option, positioning it as a potential avenue for managing multiple plantar warts.

AI/ML to Relationship Between Circadian Rhythm of Blood Pressure and Left Ventricular Hypertrophy in Patients with Hypertension.

Objective: The objective of this experiment was to investigate the relationship between the circadian rhythm of blood pressure and left ventricular hypertrophy (LVH) in patients with hypertension. Methods: A total of 500 hypertension patients with documented circadian rhythm of blood pressure were selected for this study. The researchers collected general patient data and fasting blood samples. The following parameters were measured within subgroups of hypertensive patients: age, sex ratio, BMI, fasting blood glucose, total cholesterol, triacylglycerol, HDL-C, LDL-C, duration of hypertension, antihypertensive drug usage, and statin intake. Results: The results of the study showed that LVH hypertension had a significantly higher proportion of grade 3 hypertension compared to non-LVH hypertension (P < .001). Additionally, LVH hypertension displayed higher mean systolic blood pressure levels over a 24-hour period (P = .002), during daytime (P = .029), and during nighttime (P < .001). The 24-hour pulse pressure (P < .001) and pulse pressure index (P = 0.001) were also significantly higher in patients with LVH hypertension. Furthermore, the rate of blood pressure decline at night was significantly lower in the LVH hypertension group compared to the control group (P < .001). B-type natriuretic peptide (BNP) levels (P = .034) and left ventricular mass index (LVMI) (P < .001) were significantly higher in patients with LVH hypertension compared to non-LVH patients. Conclusions: The findings of this study suggest a close association between hypertensive LVH and the weakening or disappearance of the circadian rhythm of blood pressure. It was also observed that the level of blood pressure classification and plasma BNP levels were increased in patients with LVH hypertension.

Facile General Injectable Gelatin/Metal/Tea Polyphenol Double Nanonetworks Remodel Wound Microenvironment and Accelerate Healing.

Treating the most widespread complication of diabetes: diabetic wounds poses a significant clinical obstacle due to the intricate nature of wound healing in individuals with diabetes. Here a novel approach is proposed using easily applicable injectable gelatin/metal/tea polyphenol double nanonetworks, which effectively remodel the wound microenvironment and accelerates the healing process. The gelatin(Gel) crosslink with metal ions (Zr4+ ) through the amino acids, imparting advantageous mechanical properties like self-healing, injectability, and adhesion. The nanonetwork's biological functions are further enhanced by incorporating the tea polyphenol metal nanonetwork through in situ doping of the epigallocatechin gallate (EGCG) with great antibacterial, self-healing, antioxidant, and anticancer capabilities. The in vitro and in vivo tests show that this double nanonetworks hydrogel exhibits faster cell migration and favorable anti-inflammatory and antioxidant properties and can greatly reshape the microenvironment of diabetic wounds and accelerate the wound healing rate. In addition, this hydrogel is completely degraded after subcutaneous injection for 7 days, with nondetectable cytotoxicity in H&E staining of major mice organs and the serum level of liver function indicators. Considering the above-mentioned merits of this hydrogel, it is believed that the injectable gelatin/metal/tea polyphenol double nanonetworks have broad biomedical potential, especially in diabetic wound repair and tissue engineering.

Dietary Zinc-Loaded Montmorillonite Supplementation Improves Growth Performance, Diarrhea, Intestinal Barrier Function and Regulating Gut Microbiota in Weaned Piglets.

This experiment was conducted to investigate whether low-dose zinc-loaded montmorillonite (Zn-MMT) could be used as a potential alternative for high-dose conventional ZnO in preventing diarrhea in weaned piglets. In total, 180 piglets were randomly divided to receive either of the three treatments, with six replicates per treatment and 10 piglets per replicate. The treatments were the control group (CT), the Zn-MMT group (ZM), and the ZnO group (ZO). Compared with the CT group, the ZM and ZO groups exhibited increased ADG at 14-28 days and during the whole period (p < 0.05), and a significantly decreased diarrhea rate during the whole period (p < 0.01). The activities of T-AOC and SOD were significantly increased (p < 0.05), whereas the MDA level decreased (p < 0.05) in the serum and colonic mucosa of Zn-MMT- and ZnO-fed piglets. Dietary supplementation with Zn-MMT and ZnO decreased the contents of IFN-γ, TNF-α, IL-1ß, IL-6, DAO, and LPS in the serum and colonic mucosa (p < 0.01), and increased the IL-10 level (p < 0.01). The relative mRNA expressions of TLR-4, claudin 2, Pbd1, and MUC2 were elevated in the colonic mucosa of the Zn-MMT and ZnO groups (p < 0.05). 16S rRNA gene sequencing analysis revealed that the abundances of Proteobacteria and Actinobacteria in the ileum and the populations of Ruminnococcus and Faecalibacterium in the cecum were higher in the CT group than in the other two groups. Collectively, dietary addition of Zn from Zn-MMT was comparable to Zn from ZnO for increasing growth performance, alleviating diarrhea, as well as improving mucosal barrier integrity, and regulating the gut microbiota of weaned piglets.

Daylily (Hemerocallis fulva Linn.) flowers improve sleep quality in human and reduce nitric oxide and interleukin-6 production in macrophages.

The flowers of daylily (Hemerocallis fulva Linn.) have been used as vegetable and medicinal herb for thousands of years in Taiwan and eastern Asia. Daylily flowers have been demonstrated to exert several biomedical properties. In this study, we provided the evidences show that daylily flowers exert anti-inflammatory activity in vitro and improved the sleep quality in vivo. We demonstrated that adult volunteers received water extract of daylily flowers improved sleep quality, sleep efficiency and daytime functioning, while sleep latency was reduced, compared to the adult volunteers received water. In addition, we demonstrated that aqueous and ethanol extracts of daylily flowers inhibited nitric oxide and interleukin-6 production in lipopolysaccharide-activated macrophages. Furthermore, the quantitative high performance liquid chromatography-based analysis showed the rutin content of the aqueous extract, ethanolic extract, ethyl acetate fractions of ethanolic extract, and water fractions of ethanolic extract were 7.27, 23.30, 14.71, and 57.43 ppm, respectively. These results indicate that daylily flowers have the potential to be a nutraceutical for improving inflammatory-related diseases and sleep quality in the future.

The Epidemiological Characteristics of Pulmonary Tuberculosis in Ganxian District, Ganzhou City, Jiangxi Province, China from 2011 to 2021.

Objective: This study aims to understand the characteristics and current situation of pulmonary tuberculosis (PTB) data of Ganxian District, Ganzhou City, Jiangxi Province, China from 2011 to 2021, and to provide data support and a scientific basis for the prevention and control of PTB in the county. Methods: The data were collected from the National Notifiable Disease Reporting System (NNDRS), which included information reported such as the gender, ethnicity, age, occupation, and diagnostic classification of reported PTB cases. Descriptive statistics were used to describe the characteristics of PTB patients. The SPSS 21.0 data analysis tool was used to analyze patient data, investigating the epidemiological characteristics of PTB in the region. Results: There were 4962 PTB cases reported from 2011 to 2021 in Ganxian District, with a decreasing trend. In terms of months, March and September had the highest cumulative number of reported cases, with 511 cases (10.3%) and 515 cases (10.4%), respectively. In terms of reported cases by area, Meilin Town and Jiangkou Town had the highest number, with 603 and 519 cases, respectively. In terms of gender, there were more male patients (3743 cases) than female patients (1,219 cases) , which had statistically significant differences (χ2 = 27.0, P < .001). The majority of cases were secondary PTB, with farmers being the most affected (a total of 4287 cases) compared to other occupations. In addition, most patients were aged between 40 and 70 years (a total of 2790 cases). Regarding treatment outcomes, out of 4,962 PTB patients, 2088 were cured, with a cure rate of 42.1%. Conclusion: Based on the characteristics of PTB in the area, future prevention and control work should focus on males, farmers, young students, and the elderly, while also focusing on the prevention and control of secondary PTB.

Noninvasive external therapy of traditional Chinese medicine for preventing postpartum urinary retention in women with vaginal delivery: A network meta-analysis.

BACKGROUND: To compare the effect of different noninvasive external therapies of traditional Chinese medicine (TCM) on the prevention of postpartum urinary retention (PUR) using a network meta-analysis (NMA). METHODS: A search of the China National Knowledge Infrastructure, WanFangDate, VIP, China Biomedical Literature Database, PubMed, The Cochrane Library, Embase, and Web of Science databases were reviewed for related randomized controlled trials dated between database inception and December 31, 2022, on the prevention of PUR by noninvasive TCM. Two researchers independently screened the literature, extracted the data, and assessed the risk of bias in the included studies; then, a NMA was performed using Revman5.3 software, State13.1 software, and frequency methodology. RESULTS: In total, 16 studies involving 3637 cases of parturients and 9 types of noninvasive TCM external treatments were incorporated into the NMA. The NMA results show that based on routine nursing, in terms of reducing the incidence of urinary retention, acupoint compressing combined with auricular acupressure is ranked first, followed by acupoint hot compress, acupoint massage combined with auricular acupressure, Yin-Yang therapy, acupoint massage, auricular acupressure, acupoint compressing, and routine nursing. In terms of urination time, acupoint compressing combined with auricular acupressure ranked first, followed by acupoint massage combined with auricular acupressure, acupoint electrical stimulation, acupoint compressing, TCM heating therapy, acupoint massage, auricular acupressure, and routine nursing. In terms of reducing residual urine volume after the first urination, acupoint compressing combined with auricular acupressure was ranked first, followed by auricular acupressure, acupoint compressing, acupoint massage, TCM heating therapy, and routine nursing. CONCLUSION: Current evidence shows that acupoint compressing combined with auricular acupressure may be the best noninvasive TCM treatment for preventing PUR based on routine nursing; however, further high-quality clinical randomized controlled trials are needed for validation and support.

Phenolic profile and α-glucosidase inhibitory potential of wampee (Clausena lansium (Lour.) Skeels) peel and pulp: In vitro digestion/in silico evaluations.

To investigate the changes in phenolics, flavonoids, and their bio-activities of wampee (Clausena lansium (Lour.) Skeels) during digestion, the peel and pulp were subjected to simulated in vitro digestion, encompassing oral, gastric, small intestine, and large intestine digestion stages. The peel exhibited a total release of 91.93 mg GAE/g DW of phenolics and 61.86 mg RE/g DW of flavonoids, whereas the pulp displayed a release of 27.83 mg GAE/g DW of phenolics and 8.94 mg RE/g DW of flavonoids. Notably, the phenolics and flavonoids were mostly released during the oral digestion stage for peel, while they were mostly released during the small intestine digestion stage for pulp. The results of the targeted flavonoids analysis indicated that rutin and l-epicatechin were the two most widely released compounds in each digestion step. Moreover, myricetin has been identified as the best inhibitor against α-glucosidase, probably because it formed the most H-bonds, 8, with 6 catalytic residues, which was the highest number. Furthermore, the soluble substances released from the peel exhibited significantly higher antioxidant activities and inhibitory activity against α-glucosidase (p < 0.05) compared to those from the pulp. Positive correlations were observed between the total phenolic content or total flavonoid content and the antioxidant activities (r > 0.73 (peel), > 0.61 (pulp)), as well as α-glucosidase inhibitory activity (r <  - 0.48 (peel), < -0.64 (pulp)) of peel and pulp. In conclusion, these findings provide valuable insights into the digestive characteristics and health benefits of both wampee peel and pulp.

Fluorescence-guided photoimmunotherapy using targeted nanotechnology and ML7710 to manage peritoneal carcinomatosis.

Fluorescence-guided intervention can bolster standard therapies by detecting and treating microscopic tumors before lethal recurrence. Tremendous progress in photoimmunotherapy and nanotechnology has been made to treat metastasis. However, many are lost in translation due to heterogeneous treatment effects. Here, we integrate three technological advances in targeted photo-activable multi-agent liposome (TPMAL), fluorescence-guided intervention, and laser endoscopy (ML7710) to improve photoimmunotherapy. TPMAL consists of a nanoliposome chemotherapy labeled with fluorophores for tracking and photosensitizer immunoconjugates for photoimmunotherapy. ML7710 is connected to Modulight Cloud to capture and analyze multispectral emission from TPMAL for fluorescence-guided drug delivery (FGDD) and fluorescence-guided light dosimetry (FGLD) in peritoneal carcinomatosis mouse models. FGDD revealed that TPMAL enhances drug delivery to metastases by 14-fold. ML7710 captured interpatient variability in TPMAL uptake and prompted FGLD in >50% of animals. By combining TPMAL, ML7710, and fluorescence-guided intervention, variation in treatment response was substantially reduced and tumor control improved without side effects.

Differences in psychometric characteristics of outpatients with somatic symptom disorder from general hospital biomedical (neurology/gastroenterology), traditional Chinese medicine, and psychosomatic settings.

Objective: The aim of this study is to investigate the psychometric characteristics of outpatients diagnosed with somatic symptom disorder (SSD) in biomedical, Traditional Chinese Medicine (TCM) and psychosomatic settings. Materials and methods: A total of 697 participants who completed SCID-5 and questionnaires were presented in our former study, as 3 of them had missed questionnaire data, a total of 694 participants are presented in this study. A secondary analysis of the psychometric characteristics of Somatic Symptom Disorder-B Criteria Scale (SSD-12), Somatic Symptom Severity Scale of the Patient-Health Questionnaire (PHQ-15), Patient Health Questionnaire-9 (PHQ-9) and General Anxiety Disorder-7 (GAD-7) is done to compare differences among outpatients from the three settings of medical specialties. Results: Based on the DSM-5 criteria, 90 out of 224 (40.2%) participants enrolled in biomedical departments (represented by neurology and gastroenterology departments), 44/231 (19.0%) in TCM departments, and 101/239 (42.3%) in the psychosomatic medicine departments were diagnosed with SSD. The scores of PHQ-15 in the biomedical, TCM and psychosomatic settings were 11.08 (± 4.54), 11.02 (± 5.27) and 13.26 (± 6.20); PHQ-9 were 10.43 (± 6.42), 11.20 (± 5.46) and 13.42 (± 7.32); GAD-7 were 8.52 (± 6.22), 9.57 (± 5.06) and 10.83 (± 6.24); SSD-12 were 22.26 (± 11.53), 22.98 (± 10.96) and 25.03 (± 11.54) respectively. The scores of PHQ-15, PHQ-9 and GAD-7 in SSD patients were significantly higher in psychosomatic departments than that in biomedical settings (p < 0.05). The cutoff point for SSD-12 was ≥16 in total patients; 16, 16, 17 in biomedical, TCM and psychosomatic settings, respectively. The cutoff point for PHQ-15 was found to be ≥8 in total patients; 8, 9, 11 in biomedical, TCM and psychosomatic settings, respectively. Conclusion: SSD patients from psychosomatic departments had higher level of somatic symptom severity, depression and anxiety than from TCM and biomedical settings. In our specific sample, a cutoff point of ≥16 for SSD-12 could be recommended in all three settings. But the cutoff point of PHQ-15 differs much between different settings, which was ≥8, 9, and 11 in biomedical, TCM, and psychosomatic settings, respectively.

Based on network pharmacology to explore the effect and mechanism of Yipibushen decoction in improving obese type 2 diabetes mellitus with oligoasthenotspermia.

ETHNOPHARMACOLOGICAL RELEVANCE: A traditional Chinese medicine experience compound known as Yipibushen (YPBS) decoction stimulates qi and nourishes yin, stimulates the kidney and solid essence, dissolves phlegm and eliminates stasis. YPBS decoction has proven to be successful in treating obese type 2 diabetes mellitus with oligoasthenotspermia in clinical settings. Nevertheless, the pharmacological mechanism is not understood. AIM OF THE STUDY: Investigating the mechanism of action of YPBS decoction in enhancing the obese type 2 diabetes mellitus with oligoasthenotspermia involved network pharmacology and animal validation techniques. METHODS AND MATERIALS: The YPBS Decoction' active components were found in the TCMSP database and their targets were identified using UniProtKB. Additionally, targets for the obese type 2 diabetes mellitus with oligoasthenotspermia were found in the GeneCard, DisGeNet, TTD and OMIM databases. The intersection of active ingredients, the obese type 2 diabetes mellitus with oligoasthenotspermia was chosen as the intersection target. The protein-protein interaction (PPI) network of the intersection target was built with the aid of Cytoscape 3.9.1, the core target of PPI was obtained through software analysis in R-project, GO enrichment and KEGG enrichment analysis was carried out on the core target. Finally, animal experiments were used to verify the intersection target. RESULTS: The research revealed 74 intersection targets of YPBS decoction active ingredients in the obese type 2 diabetes mellitus with oligoasthenotspermia. There were also 18 PPI core targets, GO enrichment analysis of PPI core targets involving response to oxidative stress, membrane raft, DNA-binding transcription regulator complex and other biological processes; KEGG involving endocrine resistance, PI3K/AKT signaling pathway, apoptosis and other signal pathways. In the obese type 2 diabetes mellitus with oligoasthenotspermia mice, animal studies have shown that YPBS decoction group could decrease blood glucose levels and improve insulin resistance; improve testicular function, enhance sperm count, sperm motility, sperm viability, and decrease the malformation rate. It could increase the levels of T-SOD and GSH-Px, and decrease the MDA level. In addition to this, it could improve the amount of testosterone hormone, and enhance the expression of PI3K, p-AKT and Bcl-2. CONCLUSION: By controlling the degree of oxidative stress and the PI3K/AKT/Bcl-2 pathway, YPBS decoction may enhance the obese type 2 diabetes mellitus with Oligoasthenotspermia, provide a scientific basis for clinical diagnosis and therapy.

Lipidomic investigation of the protective effects of Polygonum perfoliatum against chemical liver injury in mice.

OBJECTIVE: Recent investigations have demonstrated that Polygonum perfoliatum L. can protect against chemical liver injury, but the mechanism behind its efficacy is still unclear. Therefore, we studied the pharmacological mechanism at work in P. perfoliatum protection against chemical liver injury. METHODS: To evaluate the activity of P. perfoliatum against chemical liver injury, levels of alanine transaminase, lactic dehydrogenase, aspartate transaminase, superoxide dismutase, glutathione peroxidase and malondialdehyde were measured, alongside histological assessments of the liver, heart and kidney tissue. A nontargeted lipidomics strategy based on ultra-performance liquid chromatography quadrupole-orbitrap high-resolution mass spectrometry method was used to obtain the lipid profiles of mice with chemical liver injury and following treatment with P. perfoliatum; these profiles were used to understand the possible mechanisms behind P. perfoliatum's protective activity. RESULTS: Lipidomic studies indicated that P. perfoliatum protected against chemical liver injury, and the results were consistent between histological and physiological analyses. By comparing the profiles of liver lipids in model and control mice, we found that the levels of 89 lipids were significantly changed. In animals receiving P. perfoliatum treatment, the levels of 8 lipids were significantly improved, relative to the model animals. The results showed that P. perfoliatum extract could effectively reverse the chemical liver injury and significantly improve the abnormal liver lipid metabolism of mice with chemical liver injury, especially glycerophospholipid metabolism. CONCLUSION: Regulation of enzyme activity related to the glycerophospholipid metabolism pathway may be involved in the mechanism of P. perfoliatum's protection against liver injury. Please cite this article as: Peng L, Chen HG, Zhou X. Lipidomic investigation of the protective effects of Polygonum perfoliatum against chemical liver injury in mice. J Integr Med. 2023; 21(3): 289-301.

[Effects of different extraction methods on chemical compositions and biological activities of polysaccharides from Lycium barbarum].

In this study, five polysaccharides from Lycium barbarum(LBPs)(LBP-1-LBP-5) were selectively extracted by different extraction methods, and the chemical composition, structural characteristics, and biological activities of LBPs were explored. The results of chemical composition analysis showed that alkaloids were not detected in the five LBPs. The total polysaccharide content was(81.95%±1.6%)-(92.96%±0.76%), the uronic acid content was(8.26%±0.46%)-(24.81%±0.46%), and the protein content was(0.06%±0.03%)-(1.35%±0.13%). The monosaccharide compositions of the five LBPs were basically same, mainly including glucose, xylose, and galactose. However, there was significant difference in the content ratio of different monosaccharide. The results of infrared spectra analysis indicated that the five LBPs had typical infrared spectral characteristics of polysaccharides. The results of nuclear magnetic resonance characteristic spectrum analysis revealed that the five LBPs had two configurations of α and ß. Meanwhile, there were triple helix structures in LBP-2, LBP-3, and LBP-4, which enhanced the activities of polysaccharides. The results of activities screening suggested that the biological activities of the five LBPs were significantly different. LBP-3 showed the highest lipid oxidation clearance rate, and its antioxidant activity was equivalent to that of the positive control group. The inhibitory rate of LBP-4 on α-amylase and its activation rate of alcohol dehydrogenase were better than those of other fractions, and the inhibitory rate of LBP-4 on α-amylase was slightly higher than that of the positive control group when the mass concentration was 10 g·L~(-1). LBP-2 showed stronger inhibitory activity against α-glucosidase and hyaluronidase. This study provides references for the precise development and utilization of LBPs.

Comparative Transcriptome Analysis Provides Insights into the Molecular Mechanism Underlying the Effect of MeJA Treatment on the Biosynthesis of Saikosaponins in Bupleurum chinense DC.

Bupleurum chinense DC. is a well-known traditional Chinese medicinal plant that produces saikosaponins (SSs), which possess hepatoprotective, antipyretic, and anti-inflammatory activities. Methyl jasmonate (MeJA) is a signalling phytohormone that can increase the accumulation of SSs in the root of Bupleurum plants. However, the molecular understanding of MeJA-mediated SS biosynthesis is not clear. Therefore, it is necessary to explore the molecular mechanism underlying the response of B. chinense DC. to MeJA in roots. In this study, we performed comparative transcriptome analysis of B. chinense DC. roots with different MeJA treatment times. In total, 104,057 unigenes were identified, of which 4053 were differentially expressed genes (DEGs). Most of the DEGs were downregulated after MeJA treatment, and GO enrichment analysis showed that they were mainly related to biological processes involved in stress responses and development. A total of 88 DEGs encoding enzymes known to be involved in the SS synthesis pathway were found, and most were significantly downregulated within 24 h. Based on the DEGs, 99 transcription factors (TFs) belonging to the AP2/ERF, WRKY, bZIP, ZFP, and bHLH families with different expression patterns were also identified. Further integrated analysis indicated that 20 DEGs involved in the SS synthesis pathway and 12 DEGs encoding TFs presented strong correlations with the SS contents, and these DEGs may be critical for the biosynthesis and regulation of SSs. These findings will be critical for further study of the response of B. chinense DC. to MeJA for SS biosynthesis.

Efficacy and safety of Chinese herbal medicine children's Zibei Xuanfei syrup in treating acute trachea-bronchitis with wind-heat invading lung syndrome: A randomized, double-blind, multicentre, controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Children's Zibei Xuanfei syrup is an herbal preparation from a lifetime professor, famous old Chinese doctor, and postgraduate supervisor of medical doctor of Shandong University of Traditional Chinese Medicine. This herbal preparation promotes lung health, relieves cough, reduces phlegm, and benefits pharynx. AIM OF THE STUDY: To verify the clinical efficacy and safety of Zibei Xuanfei syrup for children in treatment of acute trachea bronchitis with wind-heat invading lung syndrome. MATERIALS AND METHODS: This was an age-stratified, block randomized, double-blind, extremely low dose parallel control, multi-center clinical trial. A total of 453 pediatric patients diagnosed with acute tracheal bronchitis in Western medicine and cough due to exogenous factors with wind-heat invading lung syndrome in Chinese medicine were enrolled. They were divided into three subgroups based on age 1∼3, 4-7, and 8-14 years old, and randomly assigned to children's Zibei Xuanfei syrup and extremely low doses of children's Zibei Xuanfei syrup (control) in a 3:1 ratio. The primary outcome was the decreased values of cough Visual Analogue Scale (VAS) score after 7 days of administration. Secondary outcomes included a decrease in cough VAS score after 3 and 5 days of the administration, and the total score of Traditional Chinese Medicine(TCM) syndrome after 3, 5, and 7 days of treatment. The chest X-ray and blood C-reactive protein were examined during screening. The safety assessment included blood urine, and stool routine, liver and kidney function of laboratory tests, and an electrocardiogram at the screening and the last visit. RESULTS: The subjects of two groups had high administration adherence (completion over 80%) (299/323, 92.6% in children's Zibei Xuanfei syrup group vs 103/107, 96.3% in the control group; p > 0.05). The children's Zibei Xuanfei syrup group was significantly better than the control group in the decreased values of cough VAS score after 7 days of administration(6.35 ± 3.45 vs 3.73 ± 3.98, p < 0.001). The subgroup analysis of the decreased value of cough VAS scores aged 1-3 years old were 5.80 ± 3.43 vs 3.75 ± 4.38 (P = 0.003), 4-7 years old was 6.30 ± 3.69 vs 2.73 ± 3.65 (P < 0.001), and 8-14 years old were 6.91 ± 3.12 vs 4.69 ± 3.75(P = 0.001)respectively. The secondary outcomes decrease values of cough VAS score of children's Zibei Xuanfei syrup group vs control group after 5 days of administration were 5.88 ± 2.90 vs 3.55 ± 3.41(P < 0.001), after 3 days of administration were 3.61 ± 2.53 vs 2.43 ± 2.56 (P < 0.001). The effective rate of the TCM symptom total score of children's Zibei Xuanfei syrup group vs control group was 91.38% vs 54.95%after 7 days of the administration, 86.93% vs 50.94% after 5 days of the administration, and 64.78% vs 40.19% after 3 days administration(each p < 0.001). There was no significant difference in Adverse Event between the two groups (59/331, 17.82% vs 15/111, 13.51%, P > 0.05). The children's Zibei Xuanfei syrup group had 5 Serious Adverse Events (incidence rate 1.21%), all of which were unrelated to the trial drug. CONCLUSION: Children's Zibei Xuanfei syrup appears to be extremely effective and safe in the treatment of acute trachea bronchitis with wind-heat invading lung syndrome. Future studies with large sample sizes will need to collect more safety data use for children.