The study on synthesis and vitro hypolipidemic activity of novel berberine derivatives nitric oxide donors.

Berberine was used as the lead compound in the present study to design and synthesize novel berberine derivatives by splicing bromine bridges of different berberine carbon chain lengths coupled nitric oxide donors, and their lipid lowering activities were assessed in a variety of ways. This experiment synthesized 17 new berberine nitric oxide donor derivatives. Compared with berberine hydrochloride, most of the compounds exhibited certain glycerate inhibitory activity, and compounds 6a, 6b, 6d, 12b and 12d showed higher inhibitory activity than berberine, with 6a, 6b and 6d having significant inhibitory activity. In addition, compound 6a linked to furazolidone nitric oxide donor showed better NO release in experiments; In further mechanistic studies, we screened and got two proteins, PCSK9 and ACLY, and docked two proteins with 17 compounds, and found that most of the compounds bound better with ATP citrate lyase (ACLY), among which there may be a strong interaction between compound 6a and ACLY, and the interaction force was better than the target drug Bempedoic Acid, which meaning that 6a may exert hypolipidemic effects by inhibiting ACLY; moreover, we also found that 6a may had the better performance in gastrointestinal absorption, blood-brain barrier permeability, Egan, Muegge class drug principle model calculation and bioavailability.

PresRecST: a novel herbal prescription recommendation algorithm for real-world patients with integration of syndrome differentiation and treatment planning.

OBJECTIVES: Herbal prescription recommendation (HPR) is a hot topic and challenging issue in field of clinical decision support of traditional Chinese medicine (TCM). However, almost all previous HPR methods have not adhered to the clinical principles of syndrome differentiation and treatment planning of TCM, which has resulted in suboptimal performance and difficulties in application to real-world clinical scenarios. MATERIALS AND METHODS: We emphasize the synergy among diagnosis and treatment procedure in real-world TCM clinical settings to propose the PresRecST model, which effectively combines the key components of symptom collection, syndrome differentiation, treatment method determination, and herb recommendation. This model integrates a self-curated TCM knowledge graph to learn the high-quality representations of TCM biomedical entities and performs 3 stages of clinical predictions to meet the principle of systematic sequential procedure of TCM decision making. RESULTS: To address the limitations of previous datasets, we constructed the TCM-Lung dataset, which is suitable for the simultaneous training of the syndrome differentiation, treatment method determination, and herb recommendation. Overall experimental results on 2 datasets demonstrate that the proposed PresRecST outperforms the state-of-the-art algorithm by significant improvements (eg, improvements of P@5 by 4.70%, P@10 by 5.37%, P@20 by 3.08% compared with the best baseline). DISCUSSION: The workflow of PresRecST effectively integrates the embedding vectors of the knowledge graph for progressive recommendation tasks, and it closely aligns with the actual diagnostic and treatment procedures followed by TCM doctors. A series of ablation experiments and case study show the availability and interpretability of PresRecST, indicating the proposed PresRecST can be beneficial for assisting the diagnosis and treatment in real-world TCM clinical settings. CONCLUSION: Our technology can be applied in a progressive recommendation scenario, providing recommendations for related items in a progressive manner, which can assist in providing more reliable diagnoses and herbal therapies for TCM clinical task.

Advances in Flavonoid Research: Sources, Biological Activities, and Developmental Prospectives.

At present, the occurrence of a large number of infectious and non-communicable diseases poses a serious threat to human health as well as to drug development for the treatment of these diseases. One of the most significant challenges is finding new drug candidates that are therapeutically effective and have few or no side effects. In this respect, the active compounds in medicinal plants, especially flavonoids, are potentially useful compounds with a wide range of pharmacological activities. They are naturally present in nature and valuable in the treatment of many infectious and non-communicable diseases. Flavonoids are divided into fourteen categories and are mainly derived from plant extraction, chemical synthesis and structural modification, and biosynthesis. The structural modification of flavonoids is an important way to discover new drugs, but biosynthesis is currently considered the most promising research direction with the potential to revolutionize the new production pipeline in the synthesis of flavonoids. However, relevant problems such as metabolic pathway analyses and cell synthesis protocols for flavonoids need to be addressed on an urgent basis. In the present review, new research techniques for assessing the biological activities of flavonoids and the mechanisms of their biological activities are elucidated and their modes of interaction with other drugs are described. Moreover, novel drug delivery systems, such as nanoparticles, bioparticles, colloidals, etc., are gradually becoming new means of addressing the issues of poor hydrophilicity, lipophilicity, poor chemical stability, and low bioavailability of flavonoids. The present review summarizes the latest research progress on flavonoids, existing problems with their therapeutic efficacy, and how these issues can be solved with the research on flavonoids.

[Synthesis and tissue distribution of bufadienolides in Bufo bufo gargarizans].

This study explored the biosynthesis of bufadienolides(BDs) in Bufo bufo gargarizans to solve the dilemma of the decreasing resources of B. bufo gargarizans and provide a theoretical basis for the sustainable utilization of the resources. Ultra-high performance liquid chromatography-Orbitrap-mass spectrometry(UHPLC-Orbitrap-MS) was employed to detect the synthesis sites of BDs in B. bufo gargarizans, and the results were verified by desorption electrospray ionization-mass spectrometry imaging(DESI-MSI) and homogenate incubation experiments. BDs in B. bufo gargarizans had the highest content in the liver and the highest concentration in the gallbladder, in addition to the parotid gland and skin, which suggested that the liver could synthesize BDs. The results of DESI-MSI also showed that BDs were mainly enriched in the liver rather than the immature parotid gland. The incubation experiment of liver homogenates demonstrated the liver of B. bufo gargarizans had the ability to synthesize BDs. This study showed that the liver was a major organ for the synthesis of BDs in B. bufo gargarizans during metamorphosis, development, and growth, which provided strong theoretical support for the biosynthesis of BDs and the sustainable utilization of B. bufo gargarizans resources.

Thermal accelerated urease-driven hyaluronan-targeted melanin nano-missile for bio-radar detection and chemodrug-free phototherapy.

Polymer-based nanomotors are attracting increasing interest in the biomedical field due to their microscopic size and kinematic properties which support overcoming biological barriers, completing cellular uptake and targeted blasting in limited spaces. However, their applications are limited by the complex viscous physiological environment and lack of sufficient biocompatibility. This manuscript firstly reports a natural melanin nano-missile of MNP@HA-EDA@Urease@AIE PS (MHUA) based on photothermally accelerated urease-driven to achieve chemodrug-free phototherapy. Compared to conventional nano-missiles that only provide driving force, this photothermally accelerated urease-driven nanomotor is independent of chemodrug to maximise biocompatibility, and achieve ideal therapeutic effect through targeted PTT/PDT. In particular, the thermal effect can not only boost the catalytic activity of urease but also achieve ideally anti-tumor effect. In addition, guided by and AIE PS, the nanomotor can generate 1O2 to achieve PDT and be traced in real time serving as an effective fluorescent bio-radar for intracellular self-reporting during cancer treatment. Finally, the targeting ability of MUHA is provided by hyaluronan. Taken together, this MHUA platform provides a simple and effective strategy for target/fluorescence radar detective-guided PTT/PDT combination, and achieves good therapeutic results without chemodrug under thermal accelerated strategy, providing a new idea for the construction of chemodrug-free nanomotor-therapy system.

MS/MS-based molecular networking discovery of sesquiterpenes from Carpesium abrotanoides L. with their cytotoxic and acetylcholinesterase inhibitory activity.

Employing an MS/MS-based molecular networking-guided strategy, three new eudesmane-type sesquiterpenes (1-3) and one undescribed pseudoguaianolide sesquiterpene (8), along with four known eudesmane-type sesquiterpene lactones (4-7) were extracted and purified from the herbs of Carpesium abrotanoides L. Structural elucidation encompassed comprehensive spectroscopic analysis, NMR calculations, DP4+ analysis, and ECD calculations. The cytotoxicity activity of all isolates was evaluated against two human hepatoma carcinoma cells (HepG2 and Hep3B) in vitro. It was demonstrated that compounds 2 and 4 showed moderate cytotoxic against HepG2 and Hep3B cells. Furthermore, all compounds were evaluated for their acetylcholinesterase (AChE) inhibitory activity. Particularly noteworthy is that, in comparison to the positive control, compound 1 demonstrated significant AChE inhibition with an inhibition rate of 77.86%. In addition, the inhibitory mechanism of compound 1 were investigated by in silico docking analyze and molecular dynamic simulation.

Research progress of astragaloside IV in treating acute kidney injury.

Acute kidney injury (AKI) is one of the most common clinical critical illnesses, with decreased glomerular filtration rate, retention of nitrogen products, water and electrolyte disorders, and acid-base imbalance as the main clinical manifestations. Presently, there is no effective treatment for acute kidney injury, but the main treatment is to cure the primary disease, remove risk factors, maintain acid-base and water-electrolyte balance, and undergo kidney replacement. However, the mortality rate is still high. Investigations and studies showed that the mortality rate of patients with acute kidney injury in the ICU is 5-80% [1]. In recent years, Chinese medicine has been widely used in acute kidney injury treatment due to its complete dialectical system and rich experience. Astragalus is a commonly used medicine in traditional Chinese medicine to treat acute kidney injury. Astragaloside IV is the main active component of traditional Chinese medicine, Astragalus membranaceus. This article summarizes the relevant studies on treating acute kidney injury with astragaloside IV.

Dual Self-Assembly of Puerarin and Silk Fibroin into Supramolecular Nanofibrillar Hydrogel for Infected Wound Treatment.

The treatment of infected wounds remains a challenging biomedical problem. Some bioactive small-molecule hydrogelators with unique rigid structures can self-assemble into supramolecular hydrogels for wound healing. However, they are still suffered from low structural stability and bio-functionality. Herein, a supramolecular hydrogel antibacterial dressing with a dual nanofibrillar network structure is proposed. A nanofibrillar network created by a small-molecule hydrogelator, puerarin extracted from the traditional Chinese medicine Pueraria, is interconnected with a secondary macromolecular silk fibroin nanofibrillar network induced by Ga ions via charge-induced supramolecular self-assembly. The resulting hydrogel features adequate mechanical strength for sustainable retention at wounds. Good biocompatibility and efficient bacterial inhibition are obtained when the Ga ion concentration is 0.05%. Otherwise, the substantial release of Ga ions and puerarin endows the hydrogel with excellent hemostatic and antioxidative properties. In vivo, evaluation of a mouse-infected wound model demonstrates that its healing effect outperformed that of a commercially available silver-containing wound dressing. The experimental group successfully achieves a 100% wound closure rate on day 10. This study sheds new light on the design of nanofibrillar hydrogels based on supramolecular self-assembly of naturally derived bioactive molecules as well as their clinical use for treating chronic infected wounds.

Positive benefit-risk ratio of Psoraleae Fructus: Comprehensive safety assessment and osteogenic effects in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoraleae Fructus (PF), the dried fruit of Psoralea corylifolia L., is a commonly used traditional medicine that has contributed to the treatment of orthopedic diseases for thousands of years in China. However, recent PF-related liver injury reports have drawn widespread attention regarding its potential hepatotoxicity risks. AIM OF THE STUDY: This study was aimed to evaluate the long-term efficacy and chronic toxicity of PF using a 26-week administration experiment on rats in order to simulate the clinical usage situation. MATERIALS AND METHODS: The PF aqueous extract was consecutively administrated to rats daily at dosages of 0.7, 2.0, and 5.6 g/kg (equivalent to 1-8 times the clinical doses for humans) for as long as 26 weeks. Samples were collected after 13, 26, and 32 weeks (withdrawal for 6 weeks) since the first administration. The chronic toxicity of PF was evaluated by conventional toxicological methods, and the efficacy of PF was evaluated by osteogenic effects in the natural growth process. RESULTS: In our experiments, only the H group (5.6 g/kg) for 26-week PF treatment demonstrated liver or kidney injury, which the injuries were reversible after 6 weeks of withdrawal. Notably, the PF treatment beyond 13 weeks showed significant benefits for bone growth and development in rats, with a higher benefit-risk ratio in female rats. CONCLUSIONS: PF displayed a promising benefit-risk ratio in the treatment and prevention of osteoporosis, a disease that lacks effective medicine so far. This is the first study to elucidate the benefit-risk balance associated with clinical dosage and long-term use of PF, thereby providing valuable insights for rational clinical use and risk control of PF.

PI3K/AKT mediated De novo fatty acid synthesis regulates RIG-1/MDA-5-dependent type I IFN responses in BVDV-infected CD8+T cells.

Bovine viral diarrhea virus (BVDV) has caused massive economic losses in the cattle business worldwide. Fatty acid synthase (FASN), a key enzyme of the fatty acid synthesis (FAS) pathway, has been shown to support virus replication. To investigate the role of fatty acids (FAs) in BVDV infection, we infected CD8+T lymphocytes obtained from healthy cattle with BVDV in vitro. During early cytopathic (CP) and noncytopathic (NCP) BVDV infection in CD8+ T cells, there is an increase in de novo lipid biosynthesis, resulting in elevated levels of free fatty acids (FFAs) and triglycerides (TG). BVDV infection promotes de novo lipid biosynthesis in a dose-dependent manner. Treatment with the FASN inhibitor C75 significantly reduces the phosphorylation of PI3K and AKT in BVDV-infected CD8+ T cells, while inhibition of PI3K with LY294002 decreases FASN expression. Both CP and NCP BVDV strains promote de novo fatty acid synthesis by activating the PI3K/AKT pathway. Further investigation shows that pharmacological inhibitors targeting FASN and PI3K concurrently reduce FFAs, TG levels, and ATP production, effectively inhibiting BVDV replication. Conversely, the in vitro supplementation of oleic acid (OA) to replace fatty acids successfully restored BVDV replication, underscoring the impact of abnormal de novo fatty acid metabolism on BVDV replication. Intriguingly, during BVDV infection of CD8+T cells, the use of FASN inhibitors prompted the production of IFN-α and IFN-ß, as well as the expression of interferon-stimulated genes (ISGs). Moreover, FASN inhibitors induce TBK-1 phosphorylation through the activation of RIG-1 and MDA-5, subsequently activating IRF-3 and ultimately enhancing the IFN-1 response. In conclusion, our study demonstrates that BVDV infection activates the PI3K/AKT pathway to boost de novo fatty acid synthesis, and inhibition of FASN suppresses BVDV replication by activating the RIG-1/MDA-5-dependent IFN response.

Ecosystem service tradeoff and synergistic relationship in the Yellow River Delta High-Efficiency Eco-Economic Zone.

Exploring the tradeoff and synergy relationship among ecosystem services in the Yellow River Delta High-Efficiency Eco-Economic Zone is of great practical significance for regional ecosystem service function zoning and high-quality development. Using the InVEST model, spatial auto-correlation and trade-off synergism (ESTD) model, we analyzed the spatial and temporal variations of five ecosystem services (habitat quality, carbon storage, soil conservation, water conservation, and water purification), as well as their trade-off and synergistic relationships at the township scale from 2000 to 2020. The results showed that habitat quality, carbon storage, and nitrogen and phosphorus output decreased as a whole from 2000 to 2020, and soil conservation and water purification increased. Habitat quality showed a distribution pattern of high in the north and low in the south, and carbon sto-rage, nitrogen and phosphorus output, soil conservation and water purification showed a pattern of low in the north and high in the south. During the study period, synergistic relationships among the five ecosystem services were predominant in both time cross-section and time period, but there were still differences, with synergistic relationships mainly between carbon storage and other services in time cross-section, and between habitat quality and other ser-vices in time period. Our results can provide theoretical guidance and practical reference for the enhancement of ecosystem services and the zoning of ecosystem functions, as well as basic support for the optimization of spatial patterns of national territory.

Effects of mindful breathing training combined with diary-based rehabilitation guidance in lung cancer patients undergoing surgery: A randomized controlled trial.

BACKGROUND AND PURPOSE: Lung cancer surgery patients experience severe physical and mental symptoms, which seriously affect their quality of life and prognosis. Mindful breathing training is a promising strategy to improve their symptoms, but its effectiveness is affected by training compliance, and diary-based rehabilitation instruction has been shown to help improve training compliance. Therefore, the aim of this study was to evaluate the effects of mindful breathing training combined with diary-based rehabilitation guidance on improving perioperative outcomes in lung cancer surgery patients. MATERIALS AND METHODS: This single-center, assessor-blinded, prospective, three-arm randomized controlled trial was conducted from November 1, 2021 to November 1, 2022. Patients diagnosed with primary non-small cell lung cancer and scheduled for thoracoscopic surgery were randomly allocated to the combined intervention group, the mindful breathing group or the control group, with 34 patients in each group. The control group received routine care, while the mindful breathing group received mindful breathing training and routine care. The combined intervention group received both mindful breathing training and diary-based rehabilitation guidance, along with routine care. RESULTS: The per-protocol analysis revealed that patients in the mindful breathing group experienced statistically significant improvements in dyspnea, fatigue and anxiety. Patients in the combined intervention group had statistically significant improvements in dyspnea, fatigue, anxiety, depression, exercise self-efficacy and training compliance. CONCLUSION: This study provides evidence that mindful breathing training combined with diary-based rehabilitation guidance can be effective in improving perioperative outcomes in lung cancer patients. It can be applied in clinical practice in the future.

Macrod1 suppresses diabetic cardiomyopathy via regulating PARP1-NAD+-SIRT3 pathway.

Diabetic cardiomyopathy (DCM), one of the most serious long-term consequences of diabetes, is closely associated with oxidative stress, inflammation and apoptosis in the heart. MACRO domain containing 1 (Macrod1) is an ADP-ribosylhydrolase 1 that is highly enriched in mitochondria, participating in the pathogenesis of cardiovascular diseases. In this study, we investigated the role of Macrod1 in DCM. A mice model was established by feeding a high-fat diet (HFD) and intraperitoneal injection of streptozotocin (STZ). We showed that Macrod1 expression levels were significantly downregulated in cardiac tissue of DCM mice. Reduced expression of Macrod1 was also observed in neonatal rat cardiomyocytes (NRCMs) treated with palmitic acid (PA, 400 µM) in vitro. Knockout of Macrod1 in DCM mice not only worsened glycemic control, but also aggravated cardiac remodeling, mitochondrial dysfunction, NAD+ consumption and oxidative stress, whereas cardiac-specific overexpression of Macrod1 partially reversed these pathological processes. In PA-treated NRCMs, overexpression of Macrod1 significantly inhibited PARP1 expression and restored NAD+ levels, activating SIRT3 to resist oxidative stress. Supplementation with the NAD+ precursor Niacin (50 µM) alleviated oxidative stress in PA-stimulated cardiomyocytes. We revealed that Macrod1 reduced NAD+ consumption by inhibiting PARP1 expression, thereby activating SIRT3 and anti-oxidative stress signaling. This study identifies Macrod1 as a novel target for DCM treatment. Targeting the PARP1-NAD+-SIRT3 axis may open a novel avenue to development of new intervention strategies in DCM. Schematic illustration of macrod1 ameliorating diabetic cardiomyopathy oxidative stress via PARP1-NAD+-SIRT3 axis.

Thermal-Accelerated Urease-Driven Bowl-Like Polydopamine Nanorobot for Targeted Photothermal/Photodynamic Antibiotic-Free Antibacterial Therapy.

The problem of antibiotic resistance seriously affects the treatment of bacterial infections, so there is an urgent need to develop novel antibiotic-independent antimicrobial strategies. Herein, a urease-driven bowl-like mesoporous polydopamine nanorobot (MPDA@ICG@Ur@Man) based on single-wavelength near-infrared (NIR) remote photothermal acceleration to achieve antibiotic-free phototherapy(photothermal therapy, PTT, plus photodynamic therapy, PDT) is first reported. The smart nanorobots can perform active movement by decomposing urea to produce carbon dioxide and ammonia. Particularly, the elevated local temperature during PTT can increase urease activity to enhance the autonomous movement and thus increase the contact between the antimicrobial substance and bacteria. Compared with a nanomotor propelled by urea only, the diffusion coefficient (De) of photothermal-accelerated nanorobots is increased from 1.10 to 1.26 µm2 s-1. More importantly, urease-driven bowl-like nanorobots with photothermal enhancement can specifically identify Escherichia coli (E. coli) and achieve simultaneous PTT/PDT at a single wavelength with 99% antibactericidal activity in vitro. In a word, the urease-driven bowl-like nanorobots guided by photothermal-accelerated strategy could provide a novel perspective for increasing PTT/PDT antibacterial therapeutic efficacy and be promising for various antibiotic-free sterilization applications.

Methyl jasmonate regulation of pectin polysaccharides in Cosmos bipinnatus roots: A mechanistic insight into alleviating cadmium toxicity.

Methyl jasmonate (MeJA), a crucial phytohormone, which plays an important role in resistance to Cadmium (Cd) stress. The cell wall (CW) of root system is the main location of Cd and plays a key role in resistance to Cd toxicity. However, the mechanism effect of MeJA on the CW composition and Cd accumulation remain unclear. In this study, the contribution of MeJA in regulating CW structure, pectin composition and Cd accumulation was investigated in Cosmos bipinnatus. Phenotypic results affirm MeJA's significant role in reducing Cd-induced toxicity in C. bipinnatus. Notably, MeJA exerts a dual impact, reducing Cd uptake in roots while increasing Cd accumulation in the CW, particularly bound to pectin. The molecular structure of pectin, mainly uronic acid (UA), correlates positively with Cd content, consistent in HC1 and cellulose, emphasizing UA as pivotal for Cd binding. Furthermore, MeJA modulates pectin methylesterase (PME) activity under Cd stress, influencing pectin's molecular structure and homogalacturonan (HG) content affecting Cd-binding capacity. Chelate-soluble pectin (CSP) within soluble pectins accumulates a substantial Cd proportion, with MeJA regulating both UA content and the minor component 3-deoxy-oct-2-ulosonic acid (Kdo) in CSP. The study delves into the intricate regulation of pectin monosaccharide composition under Cd stress, revealing insights into the CW's physical defense and Cd binding. In summary, this research provides novel insights into MeJA-specific mechanisms alleviating Cd toxicity in C. bipinnatus, shedding light on complex interactions between MeJA, and Cd accumulation in CW pectin polysaccharide.

Assembly and characterization of the complete mitochondrial genome of Ventilago leiocarpa.

KEY MESSAGE: We reported the mitochondrial genome of Ventilago leiocarpa for the first time. Two and one sites lead to the generation of stop and stat codon through editing were verified. Ventilago leiocarpa, a member of the Rhamnaceae family, is frequently utilized in traditional medicine due to the medicinal properties of its roots. In this study, we successfully assembled the mitogenome of V. leiocarpa using both BGI short reads and Nanopore long reads. This mitogenome has a total length of 331,839 bp. The annotated results showed 36 unique protein-coding, 16 tRNA and 3 rRNA genes in this mitogenome. Furthermore, we confirmed the presence of a branched structure through the utilization of long reads mapping, PCR amplification, and Sanger sequencing. Specifically, the ctg1 can form a single circular molecule or combine with ctg4 to form a linear molecule. Likewise, ctg2 can form a single circular molecule or can be connected to ctg4 to form a linear molecule. Subsequently, through a comparative analysis of the mitogenome and cpgenome sequences, we identified ten mitochondrial plastid sequences (MTPTs), including two complete protein-coding genes and five complete tRNA genes. The existence of MTPTs was verified by long reads. Colinear analysis showed that the mitogenomes of Rosales were highly divergent in structure. Finally, we identified 545 RNA editing sites involving 36 protein-coding genes by Deepred-mt. To validate our findings, we conducted PCR amplification and Sanger sequencing, which confirmed the generation of stop codons in atp9-223 and rps10-391, as well as the generation of a start codon in nad4L-2. This project reported the complex structure and RNA editing event of the V. Leiocarpa mitogenome, which will provide valuable information for the study of mitochondrial gene expression.

Rosmarinic acid mitigates acrylamide induced neurotoxicity via suppressing endoplasmic reticulum stress and inflammation in mouse hippocampus.

BACKGROUND: Acrylamide (ACR) is a widely used compound that is known to be neurotoxic to both experimental animals and humans, causing nerve damage. The widespread presence of ACR in the environment and food means that the toxic risk to human health can no longer be ignored. Rosmarinic acid (RA), a natural polyphenolic compound extracted from the perilla plant, exhibits anti-inflammatory, antioxidant, and other properties. It has also been demon strated to possess promising potential in neuroprotection. However, its role and potential mechanism in treating ACR induced neurotoxicity are still elusive. PURPOSE: This study explores whether RA can improve ACR induced neurotoxicity and its possible mechanism. METHODS: The behavioral method was used to study RA effect on ACR exposed mice's neurological function. We studied its potential mechanism through metabolomics, Nissl staining, HE staining, immunohistochemical analysis, and Western blot. RESULTS: RA pretreatment reversed the increase in mouse landing foot splay and decrease in spontaneous activity caused by 3 weeks of exposure to 50 mg/kg/d ACR. Further experiments demonstrated that RA could prevent ACR induced neuronal apoptosis, significantly downregulate nuclear factor-κB and tumor necrosis factor-α expression, and inhibit NOD-like receptor protein 3 inflammasome activation, thereby reducing inflammation as confirmed by metabolomics results. Additionally, RA treatment prevented endoplasmic reticulum stress (ERS) caused by ACR exposure, as evidenced by the reversal of significant P-IRE1α,TRAF2,CHOP expression increase. CONCLUSION: RA alleviates ACR induced neurotoxicity by inhibiting ERS and inflammation. These results provide a deeper understanding of the mechanism of ACR induced neurotoxicity and propose a potential new treatment method.

Effect of moxibustion for "nourishing the kidney and benefiting the marrow" on knee osteoarthritis. / "补肾益髓"æ³•è‰¾ç¸æ²»ç–—è†å ³èŠ‚éª¨å ³èŠ‚ç‚Žçš„ç–—æ•ˆè§‚å¯Ÿ.

OBJECTIVES: To compare the clinical effect between two acupoint regimens of moxibustion on knee osteoarthritis (KOA), and observe the influences on the serum content of interleukin 1α (IL-1α), interleukin-17A (IL-17A), tumor necrosis factor α (TNF-α), bone gla protein (BGP) and osteoprotegerin (OPG). METHODS: KOA patients were randomly divided into an observation group (40 cases, 2 cases dropped off) and a control group (40 cases, 3 cases dropped off). In the observation group, moxibustion was applied to Xiyan (EX-LE5), Dubi (ST35), Zusanli (ST36), Dazhu (BL11), Xuanzhong (GB39) and Yongquan (KI1) on the affected side. In the control group, EX-LE5, ST35 and ST36 were selected on the affected side. One session of treatment took 30 min in each group, delivered 3 times a week and the duration of treatment was 4 weeks. The scores of Western Ontario and McMaster University (WOMAC) and visual analogue scale (VAS) were observed and the serum content of IL-1α, IL-17A, TNF-α, BGP and OPG of the two groups were measured before and after treatment. RESULTS: Compared with those before treatment, the WOMAC score, VAS score and the serum content of IL-1α, IL-17A and TNF-α were decreased (P<0.05), and the content of BGP and OPG were increased (P<0.05) after treatment. Compared with the control group, the WOMAC score, VAS score and the serum content of IL-1α and TNF-α in the observation group were lower (P<0.05), and the content of BGP and OPG were higher (P<0.05). The total effective rate of the observation group was 89.5% (34/38), and that of the control group was 83.8% (31/37), with no statistically significant difference. CONCLUSIONS: Moxibustion therapy of "nourishing the kidney and benefiting the marrow" can relieve joint pain, improve joint function, reduce the level of inflammatory factors and ameliorate bone metabolic indicators. The effect of the acupoint regimen in this moxibustion therapy is better than that of the local acupoint selection.

A Social Media-Based Mindfulness Psycho-Behavioral Intervention (MCARE) for Patients With Acute Coronary Syndrome: Randomized Controlled Trial.

BACKGROUND: Psychological distress is common among patients with acute coronary syndrome (ACS) and has considerable adverse impacts on disease progression and health outcomes. Mindfulness-based intervention is a promising complementary approach to address patients' psychological needs and promote holistic well-being. OBJECTIVE: This study aims to examine the effects of a social media-based mindfulness psycho-behavioral intervention (MCARE) on psychological distress, psychological stress, health-related quality of life (HRQoL), and cardiovascular risk factors among patients with ACS. METHODS: This study was a 2-arm, parallel-group randomized controlled trial. We recruited 178 patients (mean age 58.7, SD 8.9 years; 122/178, 68.5% male) with ACS at 2 tertiary hospitals in Jinan, China. Participants were randomly assigned to the MCARE group (n=89) or control group (n=89). The 6-week intervention consisted of 1 face-to-face session (phase I) and 5 weekly WeChat (Tencent Holdings Ltd)-delivered sessions (phase II) on mindfulness training and health education and lifestyle modification. The primary outcomes were depression and anxiety. Secondary outcomes included psychological stress, HRQoL, and cardiovascular risk factors (ie, smoking status, physical activity, dietary behavior, BMI, blood pressure, blood lipids, and blood glucose). Outcomes were measured at baseline (T0), immediately after the intervention (T1), and 12 weeks after the commencement of the intervention (T2). RESULTS: The MCARE group showed significantly greater reductions in depression (T1: ß=-2.016, 95% CI -2.584 to -1.449, Cohen d=-1.28, P<.001; T2: ß=-2.089, 95% CI -2.777 to -1.402, Cohen d=-1.12, P<.001) and anxiety (T1: ß=-1.024, 95% CI -1.551 to -0.497, Cohen d=-0.83, P<.001; T2: ß=-0.932, 95% CI -1.519 to -0.346, Cohen d=-0.70, P=.002). Significantly greater improvements were also observed in psychological stress (ß=-1.186, 95% CI -1.678 to -0.694, Cohen d=-1.41, P<.001), physical HRQoL (ß=0.088, 95% CI 0.008-0.167, Cohen d=0.72, P=.03), emotional HRQoL (ß=0.294, 95% CI 0.169-0.419, Cohen d=0.81, P<.001), and general HRQoL (ß=0.147, 95% CI 0.070-0.224, Cohen d=1.07) at T1, as well as dietary behavior (ß=0.069, 95% CI 0.003-0.136, Cohen d=0.75, P=.04), physical activity level (ß=177.542, 95% CI -39.073 to 316.011, Cohen d=0.51, P=.01), and systolic blood pressure (ß=-3.326, 95% CI -5.928 to -0.725, Cohen d=-1.32, P=.01) at T2. The overall completion rate of the intervention (completing ≥5 sessions) was 76% (68/89). Positive responses to the questions of the acceptability questionnaire ranged from 93% (76/82) to 100% (82/82). CONCLUSIONS: The MCARE program generated favorable effects on psychological distress, psychological stress, HRQoL, and several aspects of cardiovascular risk factors in patients with ACS. This study provides clues for guiding clinical practice in the recognition and management of psychological distress and integrating the intervention into routine rehabilitation practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000033526; https://www.chictr.org.cn/showprojEN.html?proj=54693.

Diterpenoid tanshinones inhibit gastric cancer angiogenesis through the PI3K/Akt/mTOR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge is a kind of Chinese herbal medicine known for activating blood circulation and removing blood stasis, with the effect of cooling blood and eliminating carbuncles, and has been proven to have the effect of treating tumors. However, the inhibitory effect of Salvia miltiorrhiza Bunge extracts (Diterpenoid tanshinones) on tumors by inhibiting angiogenesis has not been studied in detail. AIM OF THE STUDY: This study aimed to investigate the anti-gastric cancer effect of diterpenoid tanshinones (DT) on angiogenesis, including the therapeutic effects and pathways. MATERIALS AND METHODS: This experiment utilized network pharmacology was used to identify relevant targets and pathways of Salvia miltiorrhiza Bunge-related components in the treatment of gastric cancer. The effects of DT on the proliferation and migration of human gastric cancer cell line SGC-7901 and human umbilical vein endothelial cell line HUVECs were evaluated, and changes in the expression of angiogenesis-related factors were measured. In vivo, experiments were conducted on nude mice to determine tumor activity, size, immunohistochemistry, and related proteins. RESULTS: The findings showed that DT could inhibit the development of gastric cancer by suppressing the proliferation of gastric cancer cells, inducing apoptosis, and inhibiting invasion and metastasis. In addition, the content of angiogenesis-related factors and proteins was significantly altered in DT-affected cells and animals. CONCLUSIONS: Results suggest that DT has potential as a therapeutic agent for the treatment of gastric cancer, as it can inhibit tumor growth and angiogenesis. It was also found that DT may affect the expression of the angiogenic factor VEGF through the PI3K/Akt/mTOR pathway, leading to the regulation of tumor angiogenesis. This study provides a new approach to the development of anti-tumor agents and has significant theoretical and clinical implications for the treatment of gastric cancer.