Higher serum chromium level may be associated with the presentation of depression in patients with metabolic dysfunction-associated fatty liver disease: evidence from NHANES survey.

Background: Depressive symptoms are frequently observed in patients with Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD), a prevalent metabolic disorder that affects many individuals. It is not yet clear whether there is an association between serum chromium levels and depression. Objective: The purpose of this research was to explore the association between serum chromium level and the manifestation of depression among patients with MAFLD. Methods: The selection of 1837 patients diagnosed with MAFLD was based on data obtained from the 2017-2018 National Health and Nutrition Examination Survey (NHANES) database in this research. The Patient Health Questionnaire-9 (PHQ-9) was employed to evaluate the severity of depression. The researchers utilized logistic regression models that were weighted for multiple variables to investigate the association between depression and serum chromium levels. Results: In our study, we found that 8.98% of US adults with MAFLD were suffering from depression at the time of evaluation. In the logistic regression model, serum chromium levels showed an inverse association with depression (OR=0.82, 95%CI: 0.69-0.96; p=0.016), this relationship remained after adjusting for fully confounding factors (OR=0.83, 95%CI: 0.71-0.97; p=0.021), subgroup analyses showed that the association between serum chromium levels and depression existed in relatively high-prevalence of depression groups. Conclusion: Patients diagnosed with MAFLD have a greater likelihood of experiencing depression, whereas individuals with higher levels of serum chromium are less likely to suffer from depression, and this association persists even after adjusting for other factors. These findings indicate supplementing chromium may be a viable treatment for their depressive symptoms.

Perioperative Treatment with Rivaroxaban and Dabigatran on Changes of Coagulation and Platelet Activation Biomarkers following Left Atrial Appendage Closure.

Insufficient data exist regarding the investigation of the impact of novel oral anticoagulants (NOACs) on coagulation activation biomarkers in the context of left atrial appendage closure (LAAC) and device-related thrombosis (DRT). The study was designed to investigate the changes and presence of coagulation activation biomarkers between different antithrombotic strategies following LAAC. A total of 120 nonvalvular atrial fibrillation patients intolerant of long-term anticoagulants, who underwent successful WATCHMAN closure implantation, were enrolled (rivaroxaban, n = 82; dabigatran, n = 38). Blood samples were obtained from left atrium (LA) and left atrial appendage (LAA) during the operation and fasting blood samples on the same day of LAAC and 45 days after discharge. The biochemical indicators, thrombin-antithrombin complex (TAT), soluble P-selectin (sP-selectin), von Willebrand factor (vWF), and CD40 ligand (CD40L), were measured by enzyme-linked immunosorbent assay. The primary endpoints of this study were the efficacy and safety characteristics of different antithrombotic strategies, including DRT incidence, stroke or transient ischemic attack, systemic embolism, and clinical major and nonmajor bleeding complications during the follow-up of 180 days. The results revealed that TAT, vWF, sP-selectin, and CD40L levels in vein were significantly reduced by 2.4% (p = 0.043), 5.0% (p < 0.001), 8.7% (p < 0.001), and 2.5% (p = 0.043) from their baseline levels after rivaroxaban treatment. Conversely, no significant changes were detected in the dabigatran group. Furthermore, the plasma levels of platelet activation biomarkers (CD40L and sP-selectin) in both LA and LAA groups were significantly lower after anticoagulation with rivaroxaban, as compared to dabigatran treatment (CD40L: 554.62 ± 155.54 vs. 445.02 ± 130.04 for LA p = 0.0013, 578.51 ± 156.28 vs. 480.13 ± 164.37 for LAA p = 0.0052; sP-selectin: 2849.07 ± 846.69 vs. 2225.54 ± 799.96 for LA p = 0.0105, 2915.52 ± 1402.40 vs. 2203.41 ± 1061.67 for LAA p = 0.0022). Notably, the present study suggests that rivaroxaban may be more effective in the prevention of DRT for patients undergoing LAAC.

Visualizing research trends and identifying hotspots of herbal components for treating cardiovascular diseases: A bibliometric analysis from 2000 to 2023.

OBJECTIVE: The objective of this study was to investigate the global research trends in herbal medicine for the treatment of cardiovascular disease (CVD) from 2000 to 2023. A bibliometric approach was employed to analyze international collaborations, knowledge structures, emerging trends, and research frontiers. METHOD: The Web of Science (WOS) core collection was utilized as the database, employing the search formula (((TS = (traditional Chinese medicine)) OR TS = (Chinese herbal medicinal ingredient)) OR TS = (Chinese herbal medicinal constituent)) AND TS = (cardiovascular disease) to conduct the search. The search period spanned from January 1, 2000, to February 14, 2023, and the literature type included articles and reviews. RESULTS: A total of 1478 papers were included in the analysis after searching the WOS database and excluding conference proceedings, news articles, retractions, editorials, and letters. China demonstrated the highest number of publications, followed by the United States and Taiwan (China). The institution with the highest publications was the Chinese Academy of Medical Sciences. China, the United States, and India were the main countries involved in research in this field, and there was significant collaboration among them. The hotspots related to herbal components for treating cardiovascular diseases from 2000 to 2023 included systematic reviews, ischemic reperfusion injury, global burden, type 2 diabetes, and protection. CONCLUSION: This paper provides a reference for the future development of herbal research in cardiovascular aspects by revealing the current status, hotspots, and trends of global herbal research in cardiovascular factors over more than 20 years. Identification of potential collaborators and institutions can assist researchers in exploring new directions for future research and discovering new perspectives for potential collaborations in this field.

[Tetramethylpyrazine regulates angiogenesis of endothelial cells in cerebral ischemic stroke injury via SIRT1/VEGFA signaling pathway].

This study aims to investigate whether tetramethylpyrazine(TMP) can stimulate angiogenesis in cerebral microvascular endothelial cells and alleviate cerebral ischemic stroke(CIS) and to explore the underlying mechanisms. In the animal study, adult Sprague-Dawley rats(n=15) were assigned into sham surgery(sham), middle cerebral artery occlusion/reperfusion(MCAO/R), and MCAO/R+TMP(intraperitoneal injection of 20 mg·kg~(-1)) groups. The neurological function was evaluated by the Z-Longa method. The cerebral infarction volume was detected by TTC staining. Enzyme-linked immunosorbent assay(ELISA) was employed to detect the expression of vascular endothelial growth factor(VEGF), angiopoietin(Ang), and platelet-derived growth factor(PDGF). Immunofluorescence staining was employed to detect Ki67 and the expression of vascular endothelial growth factor A(VEGFA) and slient information regulator 1(SIRT1). Western blot was employed to determine the expression levels of VEGFA, SIRT1, angiopoietin-2(Ang-2), and platelet-derived growth factor B(PDGFB). In the cell study, mouse brain-derived endothelial cells(Bend.3) were cultured, and the optimal concentration of TMP was determined. Then, VEGF, Ang, and PDGF were detected by ELISA after the addition of cabozantinib. Western blot was employed to measure the expression of VEGFA, Ang-2, and PDGFB. Immunofluorescence staining was used to detect CD31, CD34, and Ki67, and the proliferation, migration, and tube formation ability of Bend.3 cells were observed in vitro. Western blot and immunofluorescence staining were performed to measure the expression of SIRT1 and VEGFA after addition of the SIRT1-specific inhibitor selisistat(EX-527). The results showed that compared with the sham group, the MCAO/R group had severe neurological function damage, increased infarction volume, up-regulated expression of VEGF, VEGFA, Ang, Ang-2, PDGF, and PDGFB, and down-regulated expression of Ki67 and SIRT1(P<0.01). Compared with the MCAO/R group, the MCAO/R+TMP group presented alleviated neurological function damage, reduced infarction volume, and activated expression of VEGF, VEGFA, Ang, Ang-2, PDGF, PDGFB, Ki67, and SIRT1(P<0.01). The cell experiments showed that compared with the normal group, Bend.3 cells were activated by oxygen glucose deprivation/reoxygenation(OGD/R) treatment(P<0.05, P<0.01). Compared with the OGD/R group, the OGD/R+TMP group upregulated the expression levels of VEGF, VEGFA, Ang, Ang-2, PDGF, PDGFB, SIRT1, Ki67, CD31, and CD34, enhanced the angiogenic ability of Bend.3 cells without being inhibited by BMS or EX-527(P<0.05, P<0.01, P<0.001). The results suggest that TMP can activate the SIRT1/VEGFA signaling pathway to stimulate angiogenesis and alleviate CIS injury.

Efficacy and Safety of Chinese Medicine Resuscitation Pack for Enhanced Recovery after Bronchoscopy: A Randomized, Single-Blind, Placebo-Controlled Clinical Trial.

OBJECTIVE: To evaluate the efficacy and safety of a hospital-made resuscitation pack, a Chinese medicinal herbal compound formula designed to enhance recovery in post-bronchoscopy patients. METHODS: In this randomized, single-blind, placebo-controlled clinical trial, eligible patients were randomly assigned 1:1 to either the treatment or control groups. The patients in the treatment group applied the resuscitation pack, which contained aromatic compounded Chinese herbs. The patients in the control group applied a hospital-made, single herb placebo pack. Packs were placed on the Tiantu (CV 22) acupuncture point for 4 h as soon as the bronchoscopy finished. Efficacy indicators, such as recovery time, patients' symptoms including nausea and dizziness, and adverse events (AEs) were observed and compared. The outcome indices were evaluated at baseline, 1 and 24 h after the bronchoscopy. Subgroup analysis was further performed by patients' age and depth of sedation. RESULTS: When applying generalized estimating equations (GEE) to evaluate the intensity of post-bronchoscopy nausea and vomiting, the intensity was lower in the treatment group (163 cases) compared with the control group (162 cases; 95% CI: 0.004, 0.099, P=0.03]. Also, significantly lower intensity of nausea was observed in the 60-70 years of age subgroup (95% CI: 0.029, 0.169, P=0.006) and deep sedation subgroup (95% CI: 0.002, 0.124; P=0.04). There was no significant difference in dizziness between two groups by GEE (95% CI: -0.134, 0.297; P=0.459). In addition, no serious AEs were observed in either group. CONCLUSIONS: Our study found that the resuscitation pack markedly improved patients' symptoms by reducing nausea and vomiting after bronchoscopy without AEs, compared with placebo in the perioperative period. (Trial registration No. ChiCTR2000038299).

Ling-Gui-Zhu-Gan decoction protects against doxorubicin-induced myocardial injury by downregulating ferroptosis.

OBJECTIVE: To investigate the mechanism of Ling-Gui-Zhu-Gan decoction (LGZGD) protects against doxorubicin (DOX)-induced myocardial injury. METHODS: In vivo experiment, rats were divided into six groups: normal group, model group (15 mg/kg, DOX), Dex group(150 mg/kg, Dex), LGZGD-L group (2.1 g/kg), LGZGD-M group (4.2 g/kg), and LGZGD-H group (8.4 g/kg). We used HE and Masson staining to observe the histopathological changes, echocardiography to assess the cardiac function, and western blot and RT-qPCR to detect the expressions of Nrf2, GPX4, Fpn1, and Ptgs2. In vitro experiment, we used immunofluorescence to detect ROS production, and RT-qPCR to detect gene expression of GPX4, Fpn1, and Ptgs2. KEY FINDINGS: In vivo, LGZGD improved cardiac systolic function. LGZGD significantly reduced MDA, LDH, and CK levels, increased SOD activity, enhanced the protein expression of Nrf2, GPX4, and Fpn1, and decreased Ptgs2 levels. In vitro, LGZGD-containing serum significantly reduced ROS, increased the gene expression of GPX4 and Fpn1, and decreased the gene expression of Ptgs2. Furthermore, compared with the LGZGD (si-NC) group, the LGZGD (si-Nrf2) group had decreased gene expression of Nrf2, GPX4, and Fpn1 and increased gene expression of Ptgs2. CONCLUSIONS: LGZGD can ameliorate DOX-cardiotoxicity by activating the Nrf2 signaling pathway and inhibiting ferroptosis in cardiomyocytes.

Combined treatment of human mesenchymal stem cells and green tea extract on retinal ganglion cell regeneration in rats after optic nerve injury.

Retinal ganglion cell (RGC) death and axonal loss cause irreversible vision loss upon optic nerve (ON) injury. We have independently demonstrated that mesenchymal stem cells (MSCs) and green tea extract (GTE) promote RGC survival and axonal regeneration in rats with ON injury. Here we aimed to evaluate the combined treatment effect of human bone marrow-derived MSCs (hBM-MSCs) and GTE on RGC survival and axonal regeneration after ON injury. Combined treatment of hBM-MSCs and GTE promoted RGC survival and neurite outgrowth/axonal regeneration in ex vivo retinal explant culture and in rats after ON injury. GTE increased Stat3 activation in the retina after combined treatment, and enhanced brain-derived neurotrophic factor secretion from hBM-MSCs. Treatment of 10 µg/mL GTE would not induce hBM-MSC apoptosis, but inhibited their proliferation, migration, and adipogenic and osteogenic differentiation in vitro with reducing matrix metalloproteinase secretions. In summary, this study revealed that GTE can enhance RGC protective effect of hBM-MSCs, suggesting that stem cell priming could be a prospective strategy enhancing the properties of stem cells for ON injury treatment.

Adipose Component Transplantation: An Advanced Fat-Grafting Strategy for Facial Rejuvenation.

BACKGROUND: Autologous fat grafting is frequently used for volume augmentation and tissue regeneration. The uniform physical and biological characteristics of fat grafts, however, limit their optimal effects in various situations. Subjecting fat tissue to different mechanical processes results in adipose-derived products with distinct biological components and physical features. The present study describes a novel facial fat-grafting strategy, adipose component transplantation (ACT), that yields different adipose products that can be applied to specific injection sites. METHODS: All patients who underwent ACT were evaluated retrospectively. Fat tissue samples were fractionated into high-density fat, adipose matrix complex, stromal vascular fraction gel, and adipose collagen fragment, as described. Each of these fractions was processed and injected into indicated recipient sites. Additional SVF gel was cryopreserved and, if necessary, injected during the following 3 months. Patients were followed up after 1, 2, 3, and 6 months, and annually thereafter. RESULTS: From March of 2020 to September of 2021, 78 patients underwent whole face fat grafting using the ACT strategy. All operations and secondary injections of cryopreserved SVF gel were uneventful. There were no major complications, and final aesthetic results were satisfactory in 91% of patients. CONCLUSIONS: The ACT strategy allows specific adipose products to be applied to specific injection sites, as warranted. Adipose matrix complex is indicated for sufficient rigid support, high-density fat when large volumes are required, SVF gel for precise injection and cryopreservation, and ACF as mesotherapy for skin rejuvenation. The ACT strategy optimizes the biological functions and physical features of different adipose-derived products. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Curcumin hybrid molecules for the treatment of Alzheimer's disease: Structure and pharmacological activities.

Alzheimer's disease (AD) is the most common neurodegenerative disease among the elderly. Contemporary treatments can only relieve symptoms but fail to delay disease progression. Curcumin is a naturally derived compound that has demonstrated significant therapeutic effects in AD treatment. Recently, molecular hybridization has been utilized to combine the pharmacophoric groups present in curcumin with those of other AD drugs, resulting in a series of novel compounds that enhance the therapeutic efficacy through multiple mechanisms. In this review, we firstly provide a concise summary of various pathogenetic hypotheses of AD and the mechanism of action of curcumin in AD, as well as the concept of molecular hybridization. Subsequently, we focus on the recent development of hybrid molecules derived from curcumin, summarizing their structures and pharmacological activities, including cholinesterase inhibitory activity, Aß aggregation inhibitory activity, antioxidant activity, and other activities. The structure-activity relationships were further discussed.

Tri©DB: an integrated platform of knowledgebase and reporting system for cancer precision medicine.

BACKGROUND: With the development of cancer precision medicine, a huge amount of high-dimensional cancer information has rapidly accumulated regarding gene alterations, diseases, therapeutic interventions and various annotations. The information is highly fragmented across multiple different sources, making it highly challenging to effectively utilize and exchange the information. Therefore, it is essential to create a resource platform containing well-aggregated, carefully mined, and easily accessible data for effective knowledge sharing. METHODS: In this study, we have developed "Consensus Cancer Core" (Tri©DB), a new integrative cancer precision medicine knowledgebase and reporting system by mining and harmonizing multifaceted cancer data sources, and presenting them in a centralized platform with enhanced functionalities for accessibility, annotation and analysis. RESULTS: The knowledgebase provides the currently most comprehensive information on cancer precision medicine covering more than 40 annotation entities, many of which are novel and have never been explored previously. Tri©DB offers several unique features: (i) harmonizing the cancer-related information from more than 30 data sources into one integrative platform for easy access; (ii) utilizing a variety of data analysis and graphical tools for enhanced user interaction with the high-dimensional data; (iii) containing a newly developed reporting system for automated annotation and therapy matching for external patient genomic data. Benchmark test indicated that Tri©DB is able to annotate 46% more treatments than two officially recognized resources, oncoKB and MCG. Tri©DB was further shown to have achieved 94.9% concordance with administered treatments in a real clinical trial. CONCLUSIONS: The novel features and rich functionalities of the new platform will facilitate full access to cancer precision medicine data in one single platform and accommodate the needs of a broad range of researchers not only in translational medicine, but also in basic biomedical research. We believe that it will help to promote knowledge sharing in cancer precision medicine. Tri©DB is freely available at www.biomeddb.org , and is hosted on a cutting-edge technology architecture supporting all major browsers and mobile handsets.

A Metabolomics Study of Feces Revealed That a Disturbance of Selenium-Centered Metabolic Bioprocess Was Involved in Kashin-Beck Disease, an Osteoarthropathy Endemic to China.

Background: Kashin-Beck disease (KBD) is a distinct osteoarthropathy in China with an unclear pathogenesis. This study aims to explore whether perturbations in the intestine metabolome could be linked to KBD individuals. Methods: An investigation was conducted in KBD endemic villages and fecal samples were collected. After applying inclusion and exclusion criteria, a total of 75 subjects were enrolled for this study, including 46 KBD (including 19 Grade I KBD and 27 Grade II KBD) and 29 controls. Untargeted metabolomics analysis was performed on the platform of UHPLC-MS. PLS-DA and OPLS-DA were conducted to compare the groups and identify the differential metabolites (DMs). Pathway analysis was conducted on MPaLA platform to explore the functional implication of the DMs. Results: Metabolomics analysis showed that compared with the control group, KBD individuals have a total of 584 differential metabolites with dysregulated levels such as adrenic acid (log2FC = -1.87, VIP = 4.84, p = 7.63 × 10-7), hydrogen phosphate (log2FC = -2.57, VIP = 1.27, p = 1.02 × 10-3), taurochenodeoxycholic acid (VIP = 1.16, log2FC = -3.24, p = 0.03), prostaglandin E3 (VIP = 1.17, log2FC = 2.67, p = 5.61 × 10-4), etc. Pathway analysis revealed several significantly perturbed pathways associated with KBD such as selenium micronutrient network (Q value = 3.11 × 10-3, Wikipathways), metabolism of lipids (Q value = 8.43 × 10-4, Reactome), free fatty acid receptors (Q value = 3.99 × 10-3, Reactome), and recycling of bile acids and salts (Q value = 2.98 × 10-3, Reactome). Subgroup comparisons found a total of 267 differential metabolites were shared by KBD vs. control, KBD II vs. control, and KBD I vs. control, while little difference was found between KBD II and KBD I (only one differential metabolite detected). Conclusions: KBD individuals showed distinct metabolic features characterized by perturbations in lipid metabolism and selenium-related bioprocesses. Our findings suggest that the loss of nutrients metabolism balance in intestine was involved in KBD pathogenesis. Linking the nutrients metabolism (especially selenium and lipid) to KBD cartilage damage should be a future direction of KBD study.

Egg yolk phosphatidylcholine alleviates DSS-induced colitis in BALB/c mice.

Ulcerative colitis (UC) is a common inflammatory bowel disease, whose incidence is on the rise worldwide. The drugs commonly used for UC are often associated with a number of side effects. Therefore, the development of effective, food-borne substances for UC is in line with the current needs. Egg yolk phosphatidylcholine (EYPC) is one of the abundant lipids in egg yolk and possesses various biological activities. However, its protective effect against UC has not been clarified. In this study, the anti-UC activity of EYPC was investigated using a dextran sodium sulfate (DSS)-induced colitis model of BALB/c mice. The results showed that EYPC supplementation inhibited DSS-induced colon shortening, the spleen index and disease activity index increase and intestinal structural damage. EYPC could down-regulate the levels of TNF-α, IL-1ß, IL-6 and MPO in the colon and restore the number of goblet cells and the level of tight junction (TJ) proteins. Besides, EYPC modulated the composition of the gut microbiota, lowered the relative abundance of the pathogenic bacterium Parabacteroides and upregulated the abundance of the beneficial bacteria Alistipes and Lachnospiraceae_NK4A136_group. These results evidenced that EYPC could attenuate DSS-induced colitis in mice and had the potential to prevent and treat UC.

Recent Advances of Tumor Microenvironment-Responsive Nanomedicines-Energized Combined Phototherapy of Cancers.

Photodynamic therapy (PDT) has emerged as a powerful tumor treatment tool due to its advantages including minimal invasiveness, high selectivity and thus dampened side effects. On the other side, the efficacy of PDT is severely frustrated by the limited oxygen level in tumors, thus promoting its combination with other therapies, particularly photothermal therapy (PTT) for bolstered tumor treatment outcomes. Meanwhile, nanomedicines that could respond to various stimuli in the tumor microenvironment (TME) provide tremendous benefits for combined phototherapy with efficient hypoxia relief, tailorable drug release and activation, improved cellular uptake and intratumoral penetration of nanocarriers, etc. In this review, we will introduce the merits of combining PTT with PDT, summarize the recent important progress of combined phototherapies and their combinations with the dominant tumor treatment regimen, chemotherapy based on smart nanomedicines sensitive to various TME stimuli with a focus on their sophisticated designs, and discuss the challenges and future developments of nanomedicine-mediated combined phototherapies.

Association between whole blood essential trace elements and cognitive function in older adults.

BACKGROUND: Essential trace elements (ETEs) are essential nutrients for keeping the nervous system functioning. Associations between ETEs and cognitive function are still inconclusive and limited. OBJECTIVES: We aimed to investigate the individual and joint associations between ETEs and cognitive function among older adults. METHODS: A population (N = 2181) at an average age≥ 65 from Yiwu cohort in China was available for this study. Whole blood chromium (Cr), selenium (Se), manganese (Mn), and copper (Cu) concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS). Cognitive function was assessed using the Mini-Mental State Examination (MMSE), consisting of five specific cognitive domains: orientation, registry, attention and calculation, recall, and language and praxis. Linear regression, restricted cubic spline (RCS) analysis, and Bayesian kernel machine regression (BKMR) were used to analyze the individual and joint associations between ETEs and cognitive function. RESULTS: The association between Cr and MMSE score presented an inverted-U shape (Q3 versus Q1: ß = 0.774, 95 % CI: 0.297, 1.250; Q4 versus Q1: ß = 0.481, 95 % CI: 0.006, 0.956); and Cr was especially associated with the registry, recall, and language and praxis. Per IQR (36.32 µg/L) increase of Se was positively associated with the MMSE score (ß = 0.497, 95 % CI: 0.277, 0.717) and all five cognitive domains. The BKMR showed that the dose-response association between Se and cognitive function increased initially and then decreased with increasing Se concentration when fixed the other ETEs in median. ETEs mixture was positively associated with cognitive function, and Se (posterior inclusion probabilities, PIPs = 0.915) was the most important contributor within the ETEs mixture. CONCLUSIONS: The nonlinear association between Cr and cognitive function suggested further exploration of an appropriate concentration range for ETEs. A positive association between mixed ETEs and cognitive function is a reminder that their joint association should be considered. Further prospective studies or intervention studies are warranted to validate our findings in the future.

Beneficial effects of flavonoids on cardiovascular diseases by influencing NLRP3 inflammasome.

Cardiovascular diseases (CVDs) are a leading cause of global mortality and have a high incidence rate worldwide. The function of inflammasomes in CVDs has received a lot of attention recently, and the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome may be a new target for the prevention and treatment of CVDs. Flavonoids, which are found in food and plant extracts, inhibited inflammation in CVDs by regulating the NLRP3 inflammasome. CB-Dock was used to investigate whether 34 flavonoids from natural products acted on NLRP3 inflammasome. In brief, the PDB format of NLRP3 was selected as a protein file, and 34 flavonoids in SDF format were selected as the ligand file, and then input to CB-Dock for molecular docking. The docking results showed that epigallocatechin-3-gallate (EGCG), amentoflavone, baicalin, scutellarin, vitexin, silibinin, and puerarin had good binding affinities to NLRP3, which could be used as NLRP3 inhibitors, and aid in the discovery of lead compounds for the design and development of CVDs.

Potential Involvement of Organic Anion Transporters in Drug Interactions with Shuganning Injection, a Traditional Chinese Patent Medicine.

Traditional Chinese medicine injections have been widely used in China for the treatment of various diseases. Transporter-mediated drug-drug interactions are a major contributor to adverse drug reactions. However, the research on transporter-mediated Traditional Chinese medicine injection-drug interactions is limited. Shuganning injection is a widely used Traditional Chinese medicine injection for treating various liver diseases. In this study, we investigated the inhibitory effect of Shuganning injection and its four main ingredients (baicalin, geniposide, chlorogenic acid, and oroxylin A) on 9 drug transporters. Shuganning injection strongly inhibited organic anion transporter 1 and organic anion transporter 3 with IC50 values < 0.1% (v/v), and moderately inhibited organic anion transporter 2, organic anion transporting-polypeptide 1B1, and organic anion transporting-polypeptide 1B3 with IC50 values < 1.0%. Baicalin, the most abundant bioactive ingredient in the Shuganning injection, was identified as both an inhibitor and substrate of organic anion transporter 1, organic anion transporter 3, and organic anion transporting-polypeptide 1B3. Oroxylin A had the potential to act as both an inhibitor and substrate of organic anion transporting-polypeptide 1B1 and organic anion transporting-polypeptide 1B3. In contrast, geniposide and chlorogenic acid had no significant inhibitory effect on drug transporters. Notably, Shuganning injection markedly altered the pharmacokinetics of furosemide and atorvastatin in rats. Using Shuganning injection as an example, our findings support the implementation of transporter-mediated Traditional Chinese medicine injection-drug interactions in the development of Traditional Chinese medicine injection standards.

Zanthoxylum bungeanum seed oil inhibits tumorigenesis of human melanoma A375 by regulating CDC25A/CyclinB1/CDK1 signaling pathways in vitro and in vivo.

Background: Zanthoxylum bungeanum seed oil (ZBSO) is extracted from the seeds of the traditional Chinese medicine Z. bungeanum Maxim, which has been shown to have anti-melanoma effects. However, the specific mechanisms are not illustrated adequately. Aims: To further investigate the mechanism by which ZBSO inhibits melanoma and to provide scientific evidence to support ZBSO as a potential melanoma therapeutic candidate. Methods: CCK-8 assays were used to detect the function of ZBSO on A375 cells. Based on transcriptomics analyses, Western blot analysis was applied to determine whether an association existed in ZBSO with the CDC25A/CyclinB1/CDK1 signaling pathway. In addition, RT-qPCR and immunohistochemistry analysis validated that ZBSO has the anti-melanoma effect in a nude mouse xenograft model of human melanoma. Then, 16S rRNA sequencing was used to detect the regulation of gut microbes. Results: Cellular assays revealed that ZBSO could inhibit A375 cell viability by regulating the cell cycle pathway. Further studies presented that ZBSO could constrain CDC25A/CyclinB1/CDK1 signaling pathway in vitro and in vivo models of melanoma. ZBSO did not produce toxicity in mice, and significantly reduced tumor volume in xenotransplants of A375 cells. Genome analysis indicated that ZBSO successfully altered specific gut microbes. Conclusion: ZBSO inhibited the growth of A375 cells by regulating CDC25A/cyclinB1/CDK1 signaling pathway both in vitro and in vivo, suggesting that ZBSO may be a novel potential therapeutic agent.

Research on Mechanisms of Chinese Medicines in Prevention and Treatment of Postoperative Adhesion.

Postoperative adhesion (PA) is currently one of the most unpleasant complications following surgical procedures. Researchers have developed several new strategies to alleviate the formation of PA to a great extent, but so far, no single measure or treatment can meet the expectations and requirements of clinical patients needing complete PA prevention. Chinese medicine (CM) has been widely used for thousands of years based on its remarkable efficacy and indispensable advantages CM treatments are gradually being accepted by modern medicine. Therefore, this review summarizes the formating process of PA and the efficacy and action mechanism of CM treatments, including their pharmacological effects, therapeutic mechanisms and advantages in PA prevention. We aim to improve the understanding of clinicians and researchers on CM prevention in the development of PA and promote the in-depth development and industrialization process of related drugs.

Therapeutic application of natural products: NAD+ metabolism as potential target.

BACKGROUND: Nicotinamide adenine dinucleotide (NAD+) metabolism is involved in the entire physiopathological process and is critical to human health. Long-term imbalance in NAD+ homeostasis is associated with various diseases, including non-alcoholic fatty liver disease, diabetes mellitus, cardiovascular diseases, neurodegenerative disorders, aging, and cancer, making it a potential target for effective therapeutic strategies. Currently, several natural products that target NAD+ metabolism have been widely reported to have significant therapeutic effects, but systematic summaries are lacking. PURPOSE: To summarize the latest findings on the prevention and treatment of various diseases through the regulation of NAD+ metabolism by various natural products in vivo and in vitro models, and evaluate the toxicities of the natural products. METHODS: PubMed, Web of Science, and ScienceDirect were searched using the keywords "natural products sources," "toxicology," "NAD+ clinical trials," and "NAD+," and/or paired with "natural products" and "diseases" for studies published within the last decade until January 2023. RESULTS: We found that the natural products mainly include phenols (curcumin, cyclocurcumin, 4-hydroxybenzyl alcohol, salvianolic acid B, pterostilbene, EGCG), flavonoids (pinostrobin, apigenin, acacetin, tilianin, kaempferol, quercetin, isoliquiritigenin, luteolin, silybin, hydroxysafflor yellow A, scutellarin), glycosides (salidroside), quinones (emodin, embelin, ß-LAPachone, shikonin), terpenoids (notoginsenoside R1, ginsenoside F2, ginsenoside Rd, ginsenoside Rb1, ginsenoside Rg3, thymoquinone, genipin), pyrazines (tetramethylpyrazine), alkaloids (evodiamine, berberine), and phenylpropanoids (ferulic acid). These natural products have antioxidant, energy-producing, anti-inflammatory, anti-apoptotic and anti-aging effects, which mainly influence the NAMPT/NAD+/SIRT, AMPK/SIRT1/PGC-1α, Nrf2/HO-1, PKCs/PARPs/NF-κB, and AMPK/Nrf2/mTOR signaling pathways, thereby regulating NAD+ metabolism to prevent and treat various diseases. These natural products have been shown to be safe, tolerable and have fewer adverse effects in various in vivo and in vitro studies and clinical trials. CONCLUSION: We evaluated the toxic effects of natural products and summarized the available clinical trials on NAD+ metabolism, as well as the recent advances in the therapeutic application of natural products targeting NAD+ metabolism, with the aim to provide new insights into the treatment of multiple disorders.

Efficacy and safety of salvianolate and enoxaparin in the prevention of perioperative deep venous thrombosis in gastrointestinal surgery.

OBJECTIVE: In this study, the efficacy and safety of salvianolate were compared with enoxaparin in the prevention of perioperative deep vein thrombosis in gastrointestinal surgery. METHODS: From October 2017 to September 2019, 563 patients who underwent gastrointestinal surgery were collected. Based on the inclusion and exclusion criteria, 119 patients were divided into two groups: enoxaparin group (n = 65) and salvianolate group (n = 54). Comparisons were made regarding the outcomes: prothrombin time (PT), prothrombin activity (PTA), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), D-dimer level (D-D), platelet count (PLT), hematokrit (HCT), and incidence of deep vein thrombosis (DVT). RESULTS: The main outcomes showed no significance between enoxaparin group and salvianolate group (p > .05). The incidence of DVT in salvianolate group was 1.85%, significantly lower than that in enoxaparin group (12.3%) (p < .05). No serious adverse reactions occurred in the two groups during treatment. CONCLUSION: Compared with enoxaparin, salvianolate has an advantage in the prevention of perioperative thrombosis in gastrointestinal surgery with a lower incidence of DVT.