Pharmacological effects and target analysis of Guipi wan in the treatment of cerebral ischemia-reperfusion injury.

Guipi wan (GPW) is a traditional Chinese medicine commonly used in clinical practice, typically to treat neurological diseases such as neurasthenia and traumatic brain injury. It may have positive effects on cerebral ischemia‒reperfusion injury (cI/R). This study aimed to assess the effects of GPW in a mouse model of cI/R and find its possible targets. C57BL/6J mice were used to establish the cI/R model, and the laser speckle doppler was used to determine the success of the model. GPW was administered intragastrically for 7 days, brain tissue sections were stained with TTC, HE, and TUNEL, Western blot assay was performed to detect the effect of apoptosis-related proteins. Furthermore, we screened active ingredients from the TCM Database and constructed a compound‒target network using the Cytoscape 3.8.0 software. Moreover, we employed protein‒protein interaction and component‒target‒pathway network analyses to determine the potential components of GPW and its target genes, the key target was verified through molecular docking. Finally, we detected the influence of the downstream signaling pathway of the target through Western blot. The results showed that GPW decreased the cerebral infarction area, neurological function scores, and neuronal apoptosis in mice by regulating PI3K/AKT signaling pathway. Network analysis indicated that gamma-aminobutyric acid B receptor 1 (GABBR1) might be a potential target for the treatment of cI/R. Molecular docking indicated that 9 active components in GPW could bind to GABBR1 with desirable binding energy. This study represented the demonstratable effect of GPW in the treatment of cI/R injury and suggested GABBR1 as a potential target using network analysis.

Lotusine ameliorates propionic acid-induced autism spectrum disorder-like behavior in mice by activating D1 dopamine receptor in medial prefrontal cortex.

Autism spectrum disorder (ASD) is a multifaceted neuropsychiatric condition for which effective drug therapy for core clinical symptoms remains elusive. Lotusine, known for its neuroprotective properties in the treatment of neurological disorders, holds potential in addressing ASD. Nevertheless, its specific efficacy in ASD remains uncertain. This study aims to investigate the therapeutic potential of lotusine in ASD and elucidate the underlying molecular mechanisms. We induced an ASD mouse model through intracerebroventricular-propionic acid (ICV-PPA) injection for 7 days, followed by lotusine administration for 5 days. The efficacy of lotusine was evaluated through a battery of behavioral tests, including the three-chamber social test. The underlying mechanisms of lotusine action in ameliorating ASD-like behavior were investigated in the medial prefrontal cortex (mPFC) using whole-cell patch-clamp recordings, western blotting, immunofluorescence staining, molecular docking, and cellular thermal shift assay. The efficacy and mechanisms of lotusine were further validated in vitro. Lotusine effectively alleviated social deficits induced by ICV-PPA injection in mice by counteracting the reduction in miniature excitatory postsynaptic current frequency within the mPFC. Moreover, lotusine enhanced neuronal activity and ameliorated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor dysfunction in ICV-PPA infusion mice by upregulating c-fos, p-GluA1 Ser 845, and p-GluA1 Ser 831 protein levels within the mPFC. Our findings also suggest that lotusine may exert its effects through modulation of the D1 dopamine receptor (DRD1). Furthermore, the rescuing effects of lotusine were nullified by a DRD1 antagonist in PC12 cells. In summary, our results revealed that lotusine ameliorates ASD-like behavior through targeted modulation of DRD1, ultimately enhancing excitatory synaptic transmission. These findings highlight the potential of lotusine as a nutritional supplement in the treatment of ASD.

Effects of repetitive transcranial magnetic stimulation combined with music therapy in non-fluent aphasia after stroke: A randomised controlled study.

BACKGROUND: Although existing studies have shown that both repetitive transcranial magnetic stimulation (rTMS) and music therapy have advantages in the treatment of non-fluent aphasia, the efficacy of the combination of these two methods remains to be investigated. AIMS: To investigate the clinical efficacy of low-frequency rTMS combined with music therapy on language function and depression in patients with non-fluent aphasia after stroke. METHODS & PROCEDURES: A single-blind parallel randomised controlled trial was conducted. Sixty patients (mean duration = 93.78 days) with non-fluent aphasia after stroke were randomly divided into a traditional therapy group (n = 20), a music therapy group (n = 20) and a combined therapy group (n = 20, 1 Hz). The language function and depression were evaluated before and 3 weeks after treatment with the Chinese version of the Western Aphasia Battery scale, Boston Diagnostic Aphasia Examination scale and Stroke Aphasic Depression Questionnaire Hospital Version scale. OUTCOMES & RESULTS: The combined therapy group was significantly better in all outcomes than the traditional therapy group and was significantly better in depression than the music therapy group. The music therapy group was significantly better in repetition and depression than the traditional therapy group. Language improvement was positively correlated with depression improvement. For adverse events, only two patients in the combined therapy group showed slight dizziness during rTMS treatment and their symptoms improved after rest. CONCLUSIONS & IMPLICATIONS: Our preliminary randomised controlled study indicates that low-frequency rTMS combined with music therapy is feasible and safe in improving language function and depression in non-fluent aphasia patients after stroke. WHAT THIS PAPER ADDS: What is already known on this subject Repetitive transcranial magnetic stimulation (rTMS) and music therapy respectively have advantages in the treatment of non-fluent aphasia after stroke, but whether the combination of the two methods is more effective is still unknown. What this paper adds to the existing knowledge This is one of the first randomised control trials to investigate whether the clinical efficacy of low-frequency rTMS combined music therapy for non-fluent aphasia is better. The findings show that low-frequency rTMS combined music therapy is superior to traditional therapy in spontaneous speech, auditory comprehension, repetition, naming, aphasia quotient, functional language level and depression, and superior to music therapy in depression, while music therapy is superior to traditional therapy in repetition and depression. What are the potential or actual clinical implications of this work? Low-frequency rTMS combined music therapy may be a better method for treatment of non-fluent aphasia.

Spatholobus suberectus inhibits lipogenesis and tumorigenesis in triple-negative breast cancer via activation of AMPK-ACC and K-Ras-ERK signaling pathway.

Background and aim: Triple-negative breast cancer (TNBC) is a highly invasive type of breast cancer with a poor prognosis. Currently, there are no effective management strategies for TNBC. Earlier, our lab reported the percolation of Spatholobus suberectus for the treatment of breast cancer. Lipid metabolic reprogramming is a hallmark of cancer. However, the anti-TNBC efficiency of S. suberectus extract and its causal mechanism for preventing lipogenesis have not been fully recognized. Hence, the present study aimed to investigate the inhibitory role of S. suberectus extract on lipogenesis and tumorigenesis in TNBC in vitro and in vivo by activating AMPK-ACC and K-Ras-ERK signaling pathways using lipidomic and metabolomic techniques. Experimental procedure: Dried stems of S. suberectus extract inhibited lipogenesis and tumorigenesis and promoted fatty acid oxidation as demonstrated by the identification of the metabolites and fatty acid markers using proteomic and metabolomic analysis, qPCR, and Western blot. Results and conclusion: The results indicated that S. suberectus extract promotes fatty acid oxidation and suppresses lipogenic metabolites and biomarkers, thereby preventing tumorigenesis via the AMPK-ACC and K-Ras-ERK signaling pathways. On the basis of this preclinical evidence, we suggest that this study represents a milestone and complements Chinese medicine. Further studies remain underway in our laboratory to elucidate the active principles of S. suberectus extract. This study suggests that S. suberectus extract could be a promising therapy for TNBC.

Study on the transport and internalisation mechanism of dietary supplement nattokinase in the small intestine using animal and Caco-2 cell monolayer models.

Maintaining proper blood flow is critical to promoting good health. Nattokinase is a serine protease from Bacillus subtilis that has significant in vitro thrombolytic activity, but its mechanism as a dietary supplement to prevent thrombosis through intestinal absorption and transport is still unclear.The purpose of this study is to study the transport and internalisation mechanism of NK in the small intestine using animal models and Caco-2 cell monolayer models.This study first evaluated the preventive effect of supplementing low dose (4000 FU (Fibrin Unit)/kg, n = 6), medium dose (8000 FU/kg, n = 6), and high dose (12000 FU/kg, n = 6) of nattokinase on carrageenan induced thrombosis in mice. Subsequently, we used the rat gut sac model, ligated intestinal loop model, and Caco-2 cell uptake model to study the intestinal transport mechanism of NK.Results indicate that NK is a moderately absorbed biomolecule whose transport through enterocytes is energy- and time-dependent. Chlorpromazine, nystatin and EIPA all inhibited the endocytosis of NK to varying degrees, indicating that the endocytosis of NK in Caco-2 cells involves macropinocytosis, clathrin-mediated and caveolae-mediated pathway. These findings offer a theoretical basis for investigating the mechanism of oral NK supplementation in greater depth.

Powerful Synergy of Traditional Chinese Medicine and Aggregation-Induced Emission-Active Photosensitizer in Photodynamic Therapy.

Breast cancer (BC) remains a significant global health challenge for women despite advancements in early detection and treatment. Isoliquiritigenin (ISL), a compound derived from traditional Chinese medicine, has shown potential as an anti-BC therapy, but its low bioavailability and poor water solubility restrict its effectiveness. In this study, we created theranostic nanoparticles consisting of ISL and a near-infrared (NIR) photosensitizer, TBPI, which displays aggregation-induced emission (AIE), with the goal of providing combined chemo- and photodynamic therapies (PDT) for BC. Initially, we designed an asymmetric organic molecule, TBPI, featuring a rotorlike triphenylamine as the donor and 1-methylpyridinium iodide as the acceptor, which led to the production of reactive oxygen species in mitochondria. We then combined TBPI with ISL and encapsulated them in DSPE-PEG-RGD nanoparticles to produce IT-PEG-RGD nanoparticles, which showed high affinity for BC, better intersystem crossing (ISC) efficiency, and Förster resonance energy transfer (FRET) between TBPI and ISL. In both 4T1 BC cell line and a 4T1 tumor-bearing BC mouse model, the IT-PEG-RGD nanoparticles demonstrated excellent drug delivery, synergistic antitumor effects, enhanced tumor-killing efficacy, and reduced drug dosage and side effects. Furthermore, we exploited the optical properties of TBPI with ISL to reveal the release process and distribution of nanoparticles in cells. This study provides a valuable basis for further exploration of IT-PEG-RGD nanoparticles and their anticancer mechanisms, highlighting the potential of theranostic nanoparticles in BC treatment.

Bioinformatics analysis and identification of upregulated tumor suppressor genes associated with suppressing colon cancer progression by curcumin treatment.

Tumor suppressor genes (TSGs) are commonly downregulated in colon cancer and play a negative role in tumorigenesis and cancer progression by affecting genomic integrity, the cell cycle, and cell proliferation. Curcumin (CUR), a Chinese herb-derived phytochemical, exerts antitumor effects on colon cancer. However, it remains unclear whether CUR exerts its antitumor effects by reactivating TSGs in colon cancer. Here, we demonstrated that CUR inhibited HT29 and HCT116 proliferation and migration by cell-counting kit-8, colony-formation, and wound-healing assays. Furthermore, the comprehensive bioinformatics analysis of mRNA sequencing revealed that 3,505 genes were significantly upregulated in response to CUR in HCT116 cells. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses showed that the most upregulated genes were enriched in cancer pathways containing 37 TSGs. Five (ARHGEF12, APAF1, VHL, CEBPA, and CASP8) of the 37 upregulated TSGs were randomly selected for real-time fluorescence polymerase chain reaction and the verification results showed that these five genes were significantly reactivated after CUR treatment, suggesting that TSGs are related to CUR-mediated colon cancer inhibition. ARHGEF12 is a newly identified TSG and a potential therapeutic target for colon cancer. Furthermore, molecular docking was performed to predict the binding sites of CUR and ARHGEF12, suggesting that CUR can prevent colon cancer cell invasion and metastasis by inhibiting ARHGEF12 and RhoA binding. In conclusion, the present study reveals that CUR inhibits colon cancer cell proliferation and migration by reactivating TSGs, revealing a new mechanism and potential target for colon cancer treatment.

Effects of Chinese Medicine on Pyroptosis in Coronary Heart Disease.

Pyroptosis, an apoptotic pathway for pro-inflammatory cells, has attracted attention from researchers because of its role in the development of cardiac inflammation reactions. Chinese medicine (CM) has been given more and more attention during the pursuit of a treatment for coronary heart disease (CHD). Evidence suggests that myocardial cell pyroptosis affects the progression of CHD. Pyroptosis pathways include the canonical pyroptosis pathway mediated by the caspase-1 inflammasome and the non-canonical pyroptosis pathway induced by cytoplasmic lipopolysaccharide-activated caspase-4/5/11. The frequently studied compounds that regulate pyroptosis in CHD include astragaloside IV (AS-IV), tanshinone IIA, aucubin, cinnamaldehyde (CD), ginsenoside Rb1, paeoniflorin, apigenin, berberine (BBR), ruscogenin (Rus), and total glucosides of paeonia (TGP). The patent drugs of CM that regulate pyroptosis in CHD include the Qishen granule (QSG), the Simiao Yong'an decoction (SMYAD), the Buyang Huanwu decoction (BYHWD), and the Shexiang Baoxin pill (SBP). Therefore, this paper reviews the pathogenesis of pyroptosis, the role of pyroptosis in CHD, and the potential therapeutic roles of CMs and their active ingredients targeting cell pyroptosis in the development of CHD.

Luteolin in the Qi Bi Anshen decoction improves propionic acid-induced autism-like behavior in rats by inhibiting LRP1/MMP9.

BACKGROUND: A neurodevelopmental illness with a high frequency and unidentified pathophysiology is known as autism spectrum disorder (ASD). A research hotspot in this field is the identification of disease-specific biomarkers and drug intervention targets. Traditional Chinese medicine (TCM) can eliminate the symptoms of autism by precisely regulating human physiology. The Qi Bi Anshen decoction (QAT) is a commonly used TCM clinical drug commonly-used to treat for treating ASD. However, the primary active ingredients and underlying mechanisms of action of this decoction remain unknown. PURPOSE: This study aimed to investigate the active ingredients and pharmacodynamics of QAT in the treatment of ASD using a Sprague-Dawley rat model that resembled autism. METHODS: Autism-like rat models were established through intracerebroventricular injections of propionic acid (PPA). Subsequently, the rats were treated with QAT, and their efficacy was evaluated using the three-chamber method to analyze social interactions and grooming behavior. Additionally, open-field tests, elevated cross-maze tests, hematoxylin and eosin staining, Nissl staining, and enzyme-linked immunosorbent assays were performed; Western blot analysis was employed to determine the expression of synaptic plasticity-related proteins. Utilizing ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS), the effectiveness of active QAT components was assessed, and potential QAT targets were screened through molecular docking, surface plasmon resonance, and thermal migration experiments. To better understand the precise processes involved in treating ASD with active QAT components, in vivo and in vitro knockdown tests were also performed. RESULTS: QATexhibited a significant improvement in autism-like behavior and a notable increase in the production of proteins associated with synaptic plasticity. Furthermore, luteolin (LUT), identified as a potentially important active ingredient in QAT for treating ASD, reduced matrix metallopeptidase-9 (MMP9) expression. However, this effect was attenuated by the knockdown of low-density lipoprotein receptor-associated protein 1 (LRP1), which is the target binding site for LUT. CONCLUSIONS: LUT emerges as a potentially crucial active component of QAT in the treatment of ASD, with the ability to antagonize LRP1 and subsequently reduce MMP9 expression.

Efficacy and safety of Ginkgo biloba dropping pills in the treatment of coronary heart disease with stable angina pectoris and depression: study protocol for a randomised, placebo-controlled, parallel-group, double-blind and multicentre clinical trial.

BACKGROUND: Coronary heart disease(CHD) with stable angina pectoris is a common cardiovascular disease. It has been reported that 10%-81.4% of these patients suffer from psychological conditions,such as depression, which has been associated with more frequent angina, lower treatment satisfaction and lower perceived quality of life. Ginkgo biloba extract (GBE), the raw material of Ginkgo biloba dropping pills (GBDPs), is widely used to treat various conditions, including cardiovascular disease, ischaemic cerebrovascular disease, and depression. This clinical trial aimed to examine the efficacy and safety of GBDPs in improving the frequency of angina pectoris and the life quality of patients with stable angina pectoris and depression symptoms. METHODS: This randomised, double-blind, placebo-controlled, parallel-group and multicentre clinical trial will be conducted in four medical centres in China. We aim to recruit approximately 72 participants aged 18-75 years with depression and coronary heart disease with stable angina pectoris. Based on conventional drug treatment, participants will be randomly assignedto the treatment group (GBDPs group; n=36) or the control group (placebo group; n=36) at a 1:1 allocation ratio. After randomisation,follow-up will be done at 4 weeks, 8 weeks and 12 weeks (±3 days). Additionally, 30 healthy individuals will be enrolled to investigate the underlying pharmacological mechanisms of the effects of GBE. The primary outcomes will be the Seattle Angina Questionnaire score and the frequency of angina pectoris-related symptoms each week. The secondary outcomes will include the 36-item Short Form Health Survey quality-of-life scale, Hamilton Depression Scale and composite endpoint incidence of major adverse cardiovascular events. ETHICS AND DISSEMINATION: This trial has been approved by the Research Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine, China (approval number: ZYYECK [2020]030). Written informed consent will be obtained from all participants. The results of this trial will be publicly shared through academic conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04529148 and ChiCTR2200066908.

Dual Behavior Regulation: Tether-Free Deep-Brain Stimulation by Photothermal and Upconversion Hybrid Nanoparticles.

Optogenetics has been plagued by invasive brain implants and thermal effects during photo-modulation. Here, two upconversion hybrid nanoparticles modified with photothermal agents, named PT-UCNP-B/G, which can modulate neuronal activities via photostimulation and thermo-stimulation under near-infrared laser irradiation at 980 nm and 808 nm, respectively, are demonstrated. PT-UCNP-B/G emits visible light (410-500 nm or 500-570 nm) through the upconversion process at 980 nm, while they exhibit efficient photothermal effect at 808 nm with no visible emission and tissue damage. Intriguingly, PT-UCNP-B significantly activates extracellular sodium currents in neuro2a cells expressing light-gated channelrhodopsin-2 (ChR2) ion channels under 980-nm irradiation, and inhibits potassium currents in human embryonic kidney 293 cells expressing the voltage-gated potassium channels (KCNQ1) under 808-nm irradiation in vitro. Furthermore, deep-brain bidirectional modulation of feeding behavior is achieved under tether-free 980 or 808-nm illumination (0.8 W cm-2 ) in mice stereotactically injected with PT-UCNP-B in the ChR2-expressing lateral hypothalamus region. Thus, PT-UCNP-B/G creates new possibility of utilizing both light and heat to modulate neural activities and provides a viable strategy to overcome the limits of optogenetics.

Analysis of proanthocyanidins and flavonols in the seedpods of Chinese Antique Lotus: A rich source of antioxidants.

Antique Lotus (Nelumbo) is a perennial aquatic plant with unique historical significance and cultural value, whereas its potential economic value hasn't been fully explored. The present study showed that lotus seedpods had significantly higher antioxidant capacity than other parts by FRAP, ABTS, and ORAC assays and analyzed the proanthocyanidins and flavonols in the seedpods of Antique Lotus. Polyphenols contributed to great antioxidant activity and 51 polyphenols were identified by UPLC-TQ-MS analysis. In which, 27 compounds were identified from lotus seedpods for the first time, including 20 trimers, 5 dimers and 2 tetramers of proanthocyanidin. Total proanthocyanidins explained 70%-90% of the different antioxidant activities and the content of proanthocyanidin trimers showed the strongest correlations with the antioxidant activities. This study provided a fundamental reference for the research of polyphenols in lotus and found that Antique Lotus seedpod extracts have the promising prospects of additives used in feed and food processing.

Efficacy and safety evaluation of Shenmai injections for dilated cardiomyopathy: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Shenmai Injection (SMI), a Chinese herbal injection, is widely used in China for the adjuvant treatment of patients with dilated cardiomyopathy (DCM), yet its clinical efficacy and safety remain controversial. PURPOSE: The aim of this study was to systematically evaluate the efficacy and safety of SMI in the treatment of DCM. METHODS: Randomised controlled trials (RCTs) of SMI in the treatment of DCM were searched for and collected from the PubMed, EMBASE, Cochrane Library, SinoMed, Wan Fang, CNKI, and VIP databases between the dates of establishment of each database and July 1, 2022. The methodological quality of the included studies was assessed, while the risk of bias was based on the Cochrane Collaboration tool. All data were analysed using the R software. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was applied to rate the quality of the evidence. RESULTS: In total, 16 RCTs, including 1,455 participants, were examined in this study. Evidence showed that the combination of SMI treatment and conventional treatment appears to significantly increase the clinical efficacy rate (OR=3.65, 95%CI (2.52, 5.28), p < 0.01), improve cardiac function (e.g. increase left ventricular ejection fraction (LVEF) (MD=5.31, 95%CI (4.21, 6.40), p < 0.01), decrease left ventricular end-diastolic dimension (LVEDD) (MD=-4.57, 95% CI (-7.10, -2.04); p < 0.01) and left ventricular end-systolic diameter (LVESD) (MD=-2.46, 95% CI (-3.60, -1.33); p < 0.01), decrease brain natriuretic peptide (BNP) (MD=-215.85, 95% CI (-241.61, -190.10); p < 0.01) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (MD=-504.42, 95% CI (-687.73, -321.10); p < 0.01), and increase 6-min walk distance (6MWD) (MD=114.08, 95% CI (42.32, 185.85); p < 0.01).In addition, no serious adverse effects associated with SMI were observed during the study period, thus suggesting that SMI is safe. However, the quality of evidence for these results was rated as "very low" to "low", mainly due to the poor methodological quality of the included RCTs, the small sample size, the high heterogeneity, and potential publication bias. CONCLUSION: In the present work, we provide evidence that combined SMI therapy is beneficial and safe for improving cardiac function in patients with DCM. However, due to limitations posed by the low methodological quality of the included trials, more rigorous and high-quality RCTs are needed to provide solid evidence.

Network Pharmacology and Molecular Docking Analysis to Explore the Mechanism of Huaiqihuang-Mediated Alleviation of Henoch-Schönlein Purpura Nephritis.

Objective: Henoch-Schönlein purpura nephritis (HSPN) is considered a major cause of chronic renal failure and is the most common secondary glomerular disease in children. Huaiqihuang (HQH), a traditional Chinese herbal formula, exhibits therapeutic effects against HSPN in clinical practice. However, the potential molecular targets and mechanisms underlying HSPN treatment remain unclear. Methods: By constructing a protein-protein interaction (PPI) network, core targets related to HQH and HSPN were identified. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways were analyzed to identify the main pathways related to HSPN based on the core targets. To screen the main active ingredients of HQH against HSPN, an ingredient-target-pathway network was constructed using the top 10 main pathways associated with HSPN. Then, molecular docking was performed to explore the interactions and binding patterns between molecules and proteins. Results: Clinical data showed that HQH combined with conventional medicine significantly reduced 24-hour urine protein excretion, urine microalbumin levels, and erythrocyte counts in the urine sediment of HSPN patients. By constructing PPI models, 15 potential core targets were identified. The top 10 main pathways showed higher enrichment ratios, including the cytokine-cytokine receptor interaction and signaling pathways related to NOD-like receptor, IL-17, etc. Through the ingredient-target-pathway network and molecular docking, we revealed that five active ingredients of HQH had good affinities with three core targets, AKT1, MMP9, and SERPINE1, which may be vital in treating HSPN. Conclusions: The study preliminarily explored the active ingredients, targets, and pathways involved in HQH therapy for HSPN. The mechanism of HQH therapy may be attributed to the modulation of inflammatory response, immune response, and oxidative stress. Combined with clinical data, our results indicate that HQH is highly effective in treating HSPN.

Electroacupuncture reduces blood glucose by regulating intestinal flora in type 2 diabetic mice.

BACKGROUND: The development of diabetes is closely related to the gut microbiota in recent studies, which can be influenced by intestinal motility. A few studies report that electroacupuncture (EA) can lower blood glucose. EA can promote colonic motility and influence gut microbes. In this study, we explored the effect of the EA on blood glucose level in mice with type 2 diabetes (T2D) and its mechanism. METHODS: The T2D mice model, fecal microbiota transplantation mice model, and KitW/Wv mice model （Point mutation of mouse W locus encoding kit gene）were used to investigate the effect of EA on blood glucose as well as the mechanism; The blood glucose and insulin resistance level and the intestinal flora were evaluated. The level of intestinal junction protein, inflammatory cytokines in the serum, interstitial cells of Cajal content, and colonic motility were detected. Lastly, the IKKß/NF-κB-JNK-IRS-1-AKT pathway was explored. RESULTS: EA lowered the blood glucose level, altered the gut microbiota, and promoted colonic motility in T2D mice. EA-altered microbiota decreased the blood glucose level and insulin resistance in the antibiotics-treated diabetic mice. EA increased tight junction protein, lowered inflammatory factors, and regulated the IKKß/NF-κB-JNK-IRS-1-AKT pathway in the liver and muscles. EA could not reduce the blood glucose and regulated gut microbiota in the KitW/Wv mice model. CONCLUSIONS: EA promoted intestinal motility to regulate the intestinal flora, thereby reducing the level of systemic inflammation, and ultimately lowering the blood glucose by the IKKß/NF-κB-JNK-IRS-1-AKT signal pathway.

A Review of the Pharmacological Potential of Spatholobus suberectus Dunn on Cancer.

Spatholobus suberectus Dunn (SSD) has been extensively employed in Traditional Chinese Medicine to treat several ailments. SSD and its active compounds are effective therapeutic agents for treating a variety of diseases with negligible side effects. Therefore, we aimed to investigate its phytochemistry, pharmacology, and potential therapeutic effects exclusively in cancer prevention and treatment. Phytochemical and pharmacological information was collected and arranged in a rational order. SSD has been frequently attributed to having antioxidant, anti-diabetic, anti-inflammatory, hematopoietic, neuroprotective, antimicrobial, and anticancer properties. Evidence has indicated that the bioactive constituents in SSD have attracted increasing scientific attention due to their preventive role in cancers. Further, the present review provides the current information on the health implications of SSD, thus allowing for future clinical trials to explore its restorative benefits. All data of in vitro and animal investigations of SSD, as well as its effect on human health, were obtained from an electronic search and library database. The diverse pharmacological potential of SSD provides an opportunity for preclinical drug discovery, and this comprehensive review strongly indicates that SSD is an excellent anti-tumorigenic agent that modulates or prevents breast cancer.

Broad-spectrum antiviral activity of Spatholobus suberectus Dunn against SARS-CoV-2, SARS-CoV-1, H5N1, and other enveloped viruses.

The current COVID-19 pandemic caused by SARS-Cov-2 is responsible for more than 6 million deaths globally. The development of broad-spectrum and cost-effective antivirals is urgently needed. Medicinal plants are renowned as a complementary approach in which antiviral natural products have been established as safe and effective drugs. Here, we report that the percolation extract of Spatholobus suberectus Dunn (SSP) is a broad-spectrum viral entry inhibitor against SARS-CoV-1/2 and other enveloped viruses. The viral inhibitory activities of the SSP were evaluated by using pseudotyped SARS-CoV-1 and 2, HIV-1ADA and HXB2 , and H5N1. SSP effectively inhibited viral entry and with EC50 values ranging from 3.6 to 5.1 µg/ml. Pre-treatment of pseudovirus or target cells with SSP showed consistent inhibitory activities with the respective EC50 value of 2.3 or 2.1 µg/ml. SSP blocked both SARS-CoV-2 spike glycoprotein and the host ACE2 receptor. In vivo studies indicated that there was no abnormal toxicity and behavior in long-term SSP treatment. Based on these findings, we concluded that SSP has the potential to be developed as a drug candidate for preventing and treating COVID-19 and other emerging enveloped viruses.

Analysis of the Application Value of Ultrasound Three-Dimensional Speckle Tracking Technology Combined with Thyroid Autoantibodies and Hormones in the Diagnosis and Treatment of Graves' Disease.

Objective: The aim of the study is to evaluate the application value of three-dimensional speckle tracking imaging (3D-STI) and combined detection of thyroid autoantibodies and hormones in the diagnosis and treatment of Graves' disease. Methods: A total of 60 patients with Graves' disease enrolled in our hospital from February 2020 to February 2021 were included in the experimental group, and 60 healthy patients after a physical examination during the same period were selected as the control group. No intervention was performed on the control group, and the experimental group received conventional Graves' disease treatment. The levels of thyroid autoantibodies and hormones in the two groups before and after the treatment were measured, and the 3D-STI was performed to compare the 3D-STI strain parameters of the research objects. Results: A significantly higher level of thyroid autoantibodies in the experimental group than that in the control group before and after the treatment was found (P < 0.001), with a remarkable decline observed after the treatment (P < 0.001). The positive rate of thyroid autoantibodies in the experimental group before the treatment was significantly higher than that in the control group (P < 0.05). After the treatment, the positive rate of TRAb and TPOAb was higher than that of the control group (P < 0.05), and the positive rate of TPOAb was higher than before the treatment. The two groups showed no significant difference in the positive rate of TGAb (P > 0.05). Significant differences were observed in the thyroid hormone levels between the two groups and also between before and after the treatment (P < 0.001). The experimental group garnered significantly higher 3D-STI strain parameters than the control group before the treatment (P < 0.05); after the treatment, the hyperthyroidism of the patients was relieved with a decreased 3D-STI value, but it was still notably higher than the control group (P < 0.05). Remarkably higher positive rates of combined detection before and after the treatment in the experimental group than those in the control group were obtained (P < 0.05). Conclusion: The combined detection of 3D-STI and thyroid autoantibodies and hormones ensures a better detection rate of Graves' disease and monitors the treatment effect of patients in real time, which provides a basis for clinical diagnosis and treatment and merits clinical promotion and application.

Screening of Differentially Expressed Genes and miRNAs in Hypothalamus and Pituitary Gland of Sheep under Different Photoperiods.

The reproduction of sheep is affected by many factors such as light, nutrition and genetics. The Hypothalamic-pituitary-gonadal (HPG) axis is an important pathway for sheep reproduction, and changes in HPG axis-related gene expression can affect sheep reproduction. In this study, a model of bilateral ovarian removal and estrogen supplementation (OVX + E2) was applied to screen differentially expressed genes and miRNAs under different photoperiods using whole transcriptome sequencing and reveal the regulatory effects of the photoperiod on the upstream tissues of the HPG axis in sheep. Whole transcriptome sequencing was performed in ewe hypothalamus (HYP) and distal pituitary (PD) tissues under short photoperiod 21st day (SP21) and long photoperiod 21st day (LP21). Compared to the short photoperiod, a total of 1813 differential genes (up-regulation 966 and down-regulation 847) and 145 differential miRNAs (up-regulation 73 and down-regulation 72) were identified in the hypothalamus of long photoperiod group. Similarly, 2492 differential genes (up-regulation 1829 and down-regulation 663) and 59 differential miRNAs (up-regulation 49 and down-regulation 10) were identified in the pituitary of long photoperiod group. Subsequently, GO and KEGG enrichment analysis revealed that the differential genes and target genes of differential miRNA were enriched in GnRH, Wnt, ErbB and circadian rhythm pathways associated with reproduction. Combined with sequence complementation and gene expression correlation analysis, several miRNA-mRNA target combinations (e.g., LHB regulated by novel-414) were obtained. Taken together, these results will help to understand the regulatory effect of the photoperiod on the upstream tissues of HPG in sheep.

[Effect of wheat-grain moxibustion on the expression of 5-HT and cortisol in the serum, and MR and GR in the hippocampus in rats with hypothyroidism complicated with depression].

OBJECTIVE: To observe the effect of wheat-grain moxibustion on behavior, 5-hydroxytryptamine (5-HT) and cortisol in the serum, mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus in rats with hypothyroidism complicated with depression, and to explore the possible mechanism of wheat-grain moxibustion on improving depression in rats with hypothyroidism. METHODS: A total of 32 SPF SD rats were randomly divided into a blank group, a model group, a medication group and a wheat-grain moxibustion group, 8 rats in each group. Except for the blank group, the rats in the remaining groups were treated with intragastric administration of 0.1% propylthiouracil (PTU) suspension at 1 mL/100 g, once a day for 4 weeks to establish the rat model of hypothyroidism, and whether the rats were accompanied with depression-like behavior determined through behavioristics evaluation. The rats in the medication group were intervened with euthyrox at 0.9 mL/100 g, once a day, for 4 weeks; the rats in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14), "Mingmen" (GV 4), "Shenshu" (BL 23) and "Pishu" (BL 20), 7 cones each acupoint, once a day, six times a week for 4 weeks. After the intervention, the depression status was observed by behavioristics test; the contents of thyroid stimulating hormone (TSH), total thyroxine (TT4), 5-HT and cortisol in the serum were detected by ELISA; the protein expressions of MR and GR in hippocampus were detected by Western blot; the expressions of MR mRNA and GR mRNA in the hippocampus were detected by real-time PCR. RESULTS: Before the intervention, compared with the blank group, the scores of open field test (OFT) were decreased and the immobility time of tail suspension test (TST) was prolonged (P<0.05); the serum TSH contents were increased and TT4 contents were decreased (P<0.01) in the other three groups. After the intervention, compared with the model group, the vertical score of OFT was increased and the immobility time of forced swimming test (FST) was prolonged in the medication group (P<0.05), while the scores of three items of OFT were increased (P<0.05, P<0.01), and the immobility time of FST and TST was shortened in the wheat-grain moxibustion group (P<0.01, P<0.05). Compared with the medication group, the immobility time of TST and FST in the wheat-grain moxibustion group was shorter (P<0.05, P<0.01). Compared with the blank group, in the model group, the contents of serum TSH and cortisol were increased (P<0.01, P<0.001), while the contents of serum TT4 and 5-HT were decreased (P<0.01, P<0.001). Compared with the model group, the contents of serum TT4 and 5-HT were increased, while the contents of serum TSH and cortisol were decreased in the medication group and wheat-grain moxibustion group (P<0.01, P<0.05). Compared with the blank group, the protein and mRNA expression of MR, GR in the hippocampus in the model group was decreased (P<0.01, P<0.05, P<0.001); compared with the model group, the protein and mRNA expression of MR in the hippocampus in the medication group were increased (P<0.05), and the protein expression of MR, GR and mRNA expression of MR in the hippocampus in the wheat-grain moxibustion group were increased (P<0.05, P<0.01). Compared with the medication group, the expression of MR mRNA in the wheat-grain moxibustion group was increased (P<0.05). CONCLUSION: Wheat-grain moxibustion could significantly improve thyroid function and depression in rats with hypothyroidism. Its mechanism may be related to up-regulating the protein and mRNA expression of MR and GR in the hippocampus, and then affecting the expression of serum cortisol and 5-HT.