Baicalin attenuates neuronal damage associated with SDH activation and PDK2-PDH axis dysfunction in early reperfusion.

BACKGROUND: Energy deficiency and oxidative stress are interconnected during ischemia/reperfusion (I/R) and serve as potential targets for the treatment of cerebral ischemic stroke. Baicalin is a neuroprotective antioxidant, but the underlying mechanisms are not fully revealed. PURPOSE: This study explored whether and how baicalin rescued neurons against ischemia/reperfusion (I/R) attack by focusing on the regulation of neuronal pyruvate dehydrogenase kinase 2 (PDK2)-pyruvate dehydrogenase (PDH) axis implicated with succinate dehydrogenase (SDH)-mediated oxidative stress. STUDY DESIGN: The effect of the tested drug was explored in vitro and in vivo with the model of oxygen-glucose deprivation/reoxygenation (OGD/R) and middle cerebral artery occlusion/reperfusion (MCAO/R), respectively. METHODS: Neuronal damage was evaluated according to cell viability, infarct area, and Nissl staining. Protein levels were measured by western blotting and immunofluorescence. Gene expression was investigated by RT-qPCR. Mitochondrial status was also estimated by fluorescence probe labeling. RESULTS: SDH activation-induced excessive production of reactive oxygen species (ROS) changed the protein expression of Lon protease 1 (LonP1) and hypoxia-inducible factor-1ɑ (HIF-1ɑ) in the early stage of I/R, leading to an upregulation of PDK2 and a decrease in PDH activity in neurons and cerebral cortices. Treatment with baicalin prevented these alterations and ameliorated neuronal ATP production and survival. CONCLUSION: Baicalin improves the function of the neuronal PDK2-PDH axis via suppression of SDH-mediated oxidative stress, revealing a new signaling pathway as a promising target under I/R conditions and the potential role of baicalin in the treatment of acute ischemic stroke.

Advancements in research on the effects of panax notoginseng saponin constituents in ameliorating learning and memory disorders.

Learning and memory disorder is a cluster of symptoms caused by neuronal aging and other diseases of the central nervous system (CNS). Panax notoginseng saponins (PNS) are a series of saponins derived from the natural active ingredients of traditional Chinese medicine (TCM) that have neuroprotective effects on the central nervous system. In this paper, we review the ameliorative effects and mechanisms of Panax notoginseng saponin-like components on learning and memory disorders to provide valuable references and insights for the development of new drugs for the treatment of learning and memory disorders. Our summary results suggest that Panax ginseng saponins have significant effects on improving learning and memory disorders, and these effects and potential mechanisms are mediated by their anti-inflammatory, anti-apoptotic, antioxidant, ß-amyloid lowering, mitochondrial homeostasis in vivo, neuronal structure and function improving, neurogenesis promoting, neurotransmitter release regulating, and probiotic homeostasis in vivo activities. These findings suggest the potential of Panax notoginseng saponin-like constituents as drug candidates for improving learning and memory disorders.

Traditional uses, phytochemistry, pharmacology, toxicity and clinical application of traditional Chinese medicine Cynoglossum amabile: a review.

Cynoglossum amabile, a member of the Boraginaceae family, is a well-known traditional Chinese medicine and ethnomedicine known as Daotihu. Despite several studies confirming the presence of bioactive pyrrolizidine alkaloids such as amabiline, ambelline, echinatine, europine, and others in C. amabile, there has been no comprehensive review of its traditional uses, phytochemistry, and pharmacology thus far. This review was conducted by thoroughly examining the literature and analyzing network databases. It covers various aspects of C. amabile, including botanical characteristics, geographical distribution, traditional applications, phytochemistry, pharmacological activities, toxicology, and clinical applications. The results have shown that C. amabile has been traditionally used for medicinal, edible, and ornamental purposes in China for many centuries. The whole plant, root, and leaf of C. amabile are used by different ethnic groups, such as Lisu, Bai, Naxi, Yi, Jinuo, and Han, to treat malaria, hepatitis, dysentery, leucorrhea, tuberculosis cough, fracture, joint dislocation, trauma bleeding, and skin carbuncle abscess. A total of 47 chemical components, including alkaloids (pyrrolizidine alkaloids, PAs), sterols, organic acids, and saccharides, were isolated from C. amabile. Pharmacological studies show that the chemical extracts of C. amabile possess various biological activities, such as anti-inflammatory, anti-tumor, anti-microbial, cardiovascular effects, ganglionic action, and acetylcholinesterase inhibition. However, it is important to note that C. amabile exhibits hepatotoxicity, with its toxicity being linked to its primary PAs components. Although preliminary studies suggest potential applications in the treatment of prostate diseases and alopecia, further research is needed to validate these clinical uses. Our review highlights the traditional uses, phytochemistry, biological activity, toxicity, and clinical applications of C. amabile. It emphasizes the essential guiding role of the indigenous medicinal knowledge system in developing new drugs. Previous studies have shown that the phytochemical and pharmacological characteristics of C. amabile are significantly related to its traditional medicinal practices. Cynoglossum amabile has excellent market potential and can be further analyzed in terms of phytochemistry, pharmacology, and toxicology, which are critical for its clinical drug safety, quality evaluation, and resource development.

Idiopathic mesenteric phlebosclerosis missed by a radiologist at initial diagnosis: A case report.

BACKGROUND: Idiopathic mesenteric phlebosclerosis (IMP) is a rare type of ischemic colitis characterized by thickening of the wall of the right hemicolon and calcification, sclerosis, and fibrosis of mesenteric veins. The diagnosis of IMP is based on typical clinical features and imaging findings. We report a case of IMP that was initially missed by the radiologist. CASE SUMMARY: A 77-year-old woman was admitted to the hospital due to chronic diarrhea for over 2 months. She had been consuming Chinese patent medicines (CPM) containing fructus gardeniae for more than 15 years. Colonoscopy revealed an edematous mucosa, bluish-purple discoloration, erosions, and ulcerations throughout the colorectal area. Abdominal computed tomography (CT) showed diffuse mural thickening of the entire colorectum, with tortuous thread-like calcifications in the right hemicolon, left hemicolon, and rectum. Most of the calcifications were located in the mesenteric vein. The diagnosis of IMP was established based on medical history, colonoscopy, CT findings, and histopathological examination. The patient was treated conservatively with papaverine and rifaximin, and CPM was stopped. Her diarrhea symptoms improved, indicating the effectiveness of the treatment. Over the next several years, she took opium alkaloids for an extended period and did not require hospitalization for the aforementioned gastrointestinal disorder. CONCLUSION: IMP is a rare gastrointestinal disease affecting Asian populations, possibly related to long-term herbal medicine intake. Accurate imaging analysis is crucial for diagnosis, but insufficient understanding of the disease can lead to misdiagnosis or missed diagnosis. Treatment strategies should be personalized.

Qilong capsule prevents myocardial ischemia/reperfusion injury by inhibiting platelet activation via the platelet CD36 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Qilong capsule (QC) is developed from the traditional Chinese medicine formula Buyang Huanwu Decoction, which has been clinically used to invigorate Qi and promote blood circulation to eliminate blood stasis. Myocardial ischemia‒reperfusion injury (MIRI) can be attributed to Qi deficiency and blood stasis. However, the effects of QC on MIRI remain unclear. AIM OF THE STUDY: This study aimed to investigate the protective effect and possible mechanism of QC on platelet function in MIRI rats. MATERIALS AND METHODS: The left anterior descending artery of adult Sprague‒Dawley rats was ligated for 30 min and then reperfused for 120 min with or without QC treatment. Then, the whole blood viscosity, plasma viscosity, coagulation, platelet adhesion rate, platelet aggregation, and platelet release factors were evaluated. Platelet CD36 and its downstream signaling pathway-related proteins were detected by western blotting. Furthermore, the active components of QC and the molecular mechanism by which QC regulates platelet function were assessed via molecular docking, platelet aggregation tests in vitro and BLI analysis. RESULTS: We found that QC significantly reduced the whole blood viscosity, plasma viscosity, platelet adhesion rate, and platelet aggregation induced by ADP or AA in rats with MIRI. The inhibition of platelet activation by QC was associated with reduced levels of ß-TG, PF-4, P-selectin and PAF. Mechanistically, QC effectively attenuated the expression of platelet CD36 and thus inhibited the activation of Src, ERK5, and p38. The active components of QC apparently suppressed platelet aggregation in vitro and regulated the CD36 signaling pathway. CONCLUSIONS: QC improves MIRI-induced hemorheological disorders, which might be partly attributed to the inhibition of platelet activation via CD36-mediated platelet signaling pathways.

Effects of vitamin family members on insulin resistance and diabetes complications.

The following letter to the editor highlights the article "Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance" in World J Diabetes 2023 Oct 15; 14 (10): 1514-1523. It is necessary to explore the role of vitamin family members in insulin resistance and diabetes complications.

Disrupted de novo pyrimidine biosynthesis impairs adult hippocampal neurogenesis and cognition in pyridoxine-dependent epilepsy.

Despite seizure control by early high-dose pyridoxine (vitamin B6) treatment, at least 75% of pyridoxine-dependent epilepsy (PDE) patients with ALDH7A1 mutation still suffer from intellectual disability. It points to a need for additional therapeutic interventions for PDE beyond pyridoxine treatment, which provokes us to investigate the mechanisms underlying the impairment of brain hemostasis by ALDH7A1 deficiency. In this study, we show that ALDH7A1-deficient mice with seizure control exhibit altered adult hippocampal neurogenesis and impaired cognitive functions. Mechanistically, ALDH7A1 deficiency leads to the accumulation of toxic lysine catabolism intermediates, α-aminoadipic-δ-semialdehyde and its cyclic form, δ-1-piperideine-6-carboxylate, which in turn impair de novo pyrimidine biosynthesis and inhibit NSC proliferation and differentiation. Notably, supplementation of pyrimidines rescues abnormal neurogenesis and cognitive impairment in ALDH7A1-deficient adult mice. Therefore, our findings not only define the important role of ALDH7A1 in the regulation of adult hippocampal neurogenesis but also provide a potential therapeutic intervention to ameliorate the defective mental capacities in PDE patients with seizure control.

Effect of 24-form simplified Tai Chi on executive inhibitory control of college students: a randomized controlled trial of EEG.

Background: College students, undergoing crucial cognitive development, face challenges during the COVID-19 pandemic that impact their executive functions. While existing research indicates positive effects of Tai Chi (TC) on college students' cognitive abilities, there is a scarcity of studies investigating its impact on executive functions and frontal brain activity. Objective: This study aimed to compare the effects of 24-form simplified TC training on college students' executive functions and frontal brain electrical activity. The hypothesis posited that the TC group would exhibit superior performance compared to the control group during COVID-19 pandemic. Method: Seventy college students were randomly assigned to either TC group or control group, engaging in 36 sessions (3 sessions per week, 45 min each) over 12 weeks. Executive inhibitory control was assessed using the Stroop Color and Word Test, and resting brain electrical activity in the frontal area was recorded through Electroencephalography. Result: ACC was influenced by group, group-time interaction, and Stroop task-time interaction. RT was affected by time, task condition, task condition-time interaction, and task condition-group interaction. Notably, the TC group showed improved ACC (from 96.54 ± 3.27% to 98.90 ± 1.32%) and decreased RT (from 0.73 ± 0.12 to 0.66 ± 0.07 s), particularly in the inconsistent task. Regarding EEG band power, significant Group and Time interaction effects were found in F3-θ, F3-α, F3-ß, F4-θ, and F4-α. Moreover, within the TC group, significant increases in F3-θ band power (from 4.66 ± 3.55 to 7.71 ± 8.44) and F4-θ band power (from 4.41 ± 2.82 to 8.61 ± 9.51) (10-3·µV·Hz) were noted pre-and post-tests. In the control group, significant decreases were observed in F3-α band power (from 5.18 ± 4.61 to 2.79 ± 2.11) and F4-α band power (from 5.57 ± 6.58 to 2.48 ± 1.95) (10-3·µV·Hz). Conclusion: The pandemic-induced panic may impact frontal lobe brain activity in college students. TC training not only improves executive inhibitory control but may also enhance localized brain activity, suggesting its potential as a holistic intervention for cognitive and neurological well-being during stressful periods.

Adsorption Characteristics of Ball Milling-Modified Chinese Medicine Residue Biochar Toward Quercetin.

Using traditional Chinese medicine residues as raw materials, different biochars (BC) were prepared through oxygen-limited pyrolysis at 300 °C, 500 °C, and 700 °C, and BC was ball-milled to produce ball-milled biochar (BMC). Using these adsorbents to adsorb the allelopathic autotoxic substance quercetin. The physical and chemical properties of various biochars derived from traditional Chinese medicine residues were characterized using the Brunauer-Emmett-Teller-N2 surface areas (BET), scanning electron microscopy (SEM), Fourier transform IR spectroscopy (FTIR), X-ray diffraction (XRD), and Raman spectroscopy (Raman). The study investigated the effects of the initial pH value, different humic acid concentrations, and multiple adsorption-desorption experiments on the removal of quercetin from the solution. The article discusses the adsorption mechanism of quercetin in solution by biochar from a traditional Chinese medicine residue, based on the results of adsorption kinetics and adsorption isotherm fitting. The findings indicate that increasing the pyrolysis temperature reduces the oxygen-containing functional groups of BC, enhances the aromaticity, and stabilizes the carbon structure. The pore structure of BMC becomes more complex after ball milling, which increases the number of oxygen-containing functional groups on the surface. Among the samples tested, BMC700 exhibits the best adsorption performance, with an adsorption capacity of 293.3 mg·g-1 at 318 K. The adsorption process of quercetin by BMC700 follows the pseudo-second-order kinetic model and the Freundlich adsorption isotherm model. The process is primarily a form of multimolecular layer adsorption. Its mechanism involves the pore-filling effect, hydrogen-bonding interaction, electrostatic interaction, and π-π coexistence, as well as the yoke effect. Additionally, they are highly recyclable and show promise in addressing continuous cropping issues.

Engineering a hyaluronic acid-encapsulated tumor-targeted nanoplatform with sensitized chemotherapy and a photothermal effect for enhancing tumor therapy.

Chemotherapy remains one of the most widely used cancer treatment modalities in clinical practice. However, the characteristic microenvironment of solid tumors severely limits the anticancer efficacy of chemotherapy. In addition, a single treatment modality or one death pathway reduces the antitumor outcome. Herein, tumor-targeting O2 self-supplied nanomodules (CuS@DOX/CaO2-HA) are proposed that not only alleviate tumor microenvironmental hypoxia to promote the accumulation of chemotherapeutic drugs in tumors but also exert photothermal effects to boost drug release, penetration and combination therapy. CuS@DOX/CaO2-HA consists of copper sulfide (CuS)-loaded calcium peroxide (CaO2) and doxorubicin (DOX), and its surface is further modified with HA. CuS@DOX/CaO2-HA underwent photothermal treatment to release DOX and CaO2. Hyperthermia accelerates drug penetration to enhance chemotherapeutic efficacy. The exposed CaO2 reacts with water to produce Ca2+, H2O2 and O2, which sensitizes cells to chemotherapy through mitochondrial damage caused by calcium overload and a reduction in drug efflux via the alleviation of hypoxia. Moreover, under near infrared (NIR) irradiation, CuS@DOX/CaO2-HA initiates a pyroptosis-like cell death process in addition to apoptosis. In vivo, CuS@DOX/CaO2-HA demonstrated high-performance antitumor effects. This study provides a new strategy for synergistic enhancement of chemotherapy in hypoxic tumor therapy via combination therapy and multiple death pathways.

Emodin-8-O-ß-D-glucopyranoside-induced hepatotoxicity and gender differences in zebrafish as revealed by integration of metabolomics and transcriptomics.

BACKGROUND: Emodin-8-O-ß-D-glucopyranoside (Em8G) is an active ingredient of traditional Chinese medicine Rhei Radix et Rhizoma and Polygonum multiflorum Thunb.. And it caused hepatotoxicity, while the underlying mechanism was not clear yet. PURPOSE: We aimed to explore the detrimental effects of Em8G on the zebrafish liver through the metabolome and transcriptome integrated analysis. STUDY DESIGN AND METHODS: In this study, zebrafish larvae were used in acute toxicity tests to reveal the hepatotoxicity of Em8G. Adult zebrafish were then used to evaluate the gender differences in hepatotoxicity induced by Em8G. Integration of transcriptomic and metabolomic analysis was used further to explore the molecular mechanisms underlying gender differences in hepatotoxicity. RESULTS: Our results showed that under non-lethal concentration exposure conditions, hepatotoxicity was observed in Em8G-treated zebrafish larvae, including changes in liver transmittance, liver area, hepatocyte apoptosis and hepatocyte vacuolation. Male adult zebrafish displayed a higher Em8G-induced hepatotoxicity than female zebrafish, as demonstrated by the higher mortality and histopathological alterations. The results of transcriptomics combined with metabolomics showed that Em8G mainly affected carbohydrate metabolism (such as TCA cycle) in male zebrafish and amino acid metabolism (such as arginine and proline metabolism) in females, suggesting that the difference of energy metabolism disorder may be the potential mechanism of male and female liver toxicity induced by Em8G. CONCLUSIONS: This study provided the direct evidence for the hepatotoxicity of Em8G to zebrafish models in vivo, and brought a new insight into the molecular mechanisms of Em8G hepatotoxicity, which can guide the rational application of this phytotoxin. In addition, our findings revealed gender differences in the hepatotoxicity of Em8G to zebrafish, which is related to energy metabolism and provided a methodological reference for evaluating hepatotoxic drugs with gender differences.

Assessing the hepatotoxicity of phosphogypsum leachate in zebrafish (Danio rerio).

The improper disposal of large amounts of phosphogypsum generated during the production process of the phosphorus chemical industry (PCI) still exists. The leachate formed by phosphogypsum stockpiles could pose a threat to the ecological environment and human health. Nevertheless, information regarding the harmful effects of phosphogypsum leachate on organisms is still limited. Herein, the physicochemical characteristics of phosphogypsum leachate were analyzed, and its toxicity effect on zebrafish (Danio rerio), particularly in terms of hepatotoxicity and potential mechanisms, were evaluated. The results indicated that P, NH3-N, TN, F-, As, Cd, Cr, Co, Ni, Zn, Mn, and Hg of phosphogypsum leachate exceeded the V class of surface water environmental quality standards (GB 3838-2002) to varying degrees. Acute toxicity test showed that the 96 h LC50 values of phosphogypsum leachate to zebrafish was 2.08 %. Under exposure to phosphogypsum leachate, zebrafish exhibited concentration-dependent liver damage, characterized by vacuolization and infiltration of inflammatory cells. The increased in Malondialdehyde (MDA) content and altered activities of antioxidant enzymes in the liver indicated the induction of oxidative stress and oxidative damage. The expression of apoptosis-related genes (P53, PUMA, Caspase3, Bcl-2, and Bax) were up-regulated at low dosage group and down-regulated at medium and high dosage groups, suggesting the occurrence of hepatocyte apoptosis or necrosis. Additionally, phosphogypsum leachate influenced the composition of the zebrafish gut microbiota by reducing the relative abundance of Bacteroidota, Aeromonas, Flavobacterium, Vibrio, and increasing that of Rhodobacter and Pirellula. Correlation analysis revealed that gut microbiota dysbiosis was associated with phosphogypsum leachate-induced hepatotoxicity. Altogether, exposure to phosphogypsum leachate caused liver damage in zebrafish, likely through oxidative stress and apoptosis, with the intestinal flora also playing a significant role. These findings contribute to understanding the ecological toxicity of phosphogypsum leachate and promote the sustainable development of PCI.

Application of Biotechniques for In Vitro Virus and Viroid Elimination in Pome Fruit Crops.

Sustainable production of pome fruit crops is dependent upon having virus-free planting materials. The production and distribution of plants derived from virus- and viroid-negative sources is necessary not only to control pome fruit viral diseases but also for sustainable breeding activities, as well as the safe movement of plant materials across borders. With variable success rates, different in vitro-based techniques, including shoot tip culture, micrografting, thermotherapy, chemotherapy, and shoot tip cryotherapy, have been employed to eliminate viruses from pome fruits. Higher pathogen eradication efficiencies have been achieved by combining two or more of these techniques. An accurate diagnosis that confirms complete viral elimination is crucial for developing effective management strategies. In recent years, considerable efforts have resulted in new reliable and efficient virus detection methods. This comprehensive review documents the development and recent advances in biotechnological methods that produce healthy pome fruit plants. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Interactive scalp acupuncture combined with suspension digital occupational therapy for upper limb motor dysfunction after stroke: a multi-center randomized controlled trial. / äº’åŠ¨å¼å¤´é’ˆç»“åˆæ‚¬åŠä¸‹æ•°å­—ä½œä¸šç–—æ³•æ²»ç–—è„‘å’ä¸­åŽä¸Šè‚¢è¿åŠ¨åŠŸèƒ½éšœç¢ï¼šå¤šä¸­å¿ƒéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe the effects of interactive scalp acupuncture on upper limb motor function and activities of daily living in patients with upper limb motor dysfunction after stroke. METHODS: One hundred and twenty patients with upper limb motor dysfunction after stroke were randomly divided into an observation group(60 cases, 2 cases dropped out)and a control group(60 cases, 1 case dropped out). Both groups were treated with routine medication and rehabilitation. The observation group was treated with interactive scalp acupuncture combined with suspension digital occupational therapy, interactive scalp acupuncture was applied at middle 2/5 of the parietal and temporal anterior oblique line, middle 2/5 of the parietal and temporal posterior oblique line and second lateral line of parietal of the hemiparalysis contralateral side, 30 min each time.The control group was treated with suspension digital occupational therapy alone. The treatment was given once a day, 5 times a week for 4 weeks in the two groups. The scores of Fugl-Meyer assessment scale of upper extremity(FMA-UE), action research arm test(ARAT), the modified Barthel index (MBI) and surface electromyography(sEMG)signal of the biceps and triceps on the affected side were observed before and after treatment in the two groups, and the clinical efficacy was evaluated. RESULTS: After treatment, the FMA-UE, ARAT and MBI scores were increased compared with those before treatment in both groups(P<0.05), the changes of the observation group were greater than those in the control group(P<0.05). After treatment, the integrated electromyography(iEMG)value and root mean square(RMS)value of the biceps and triceps on the affected side during elbow flexion and extension were increased compared with those before treatment in both groups(P<0.05), the changes of the observation group were greater than those in the control group(P<0.05). The total effective rate was 94.8%(55/58) in the observation group, which was higher than 83.1%(49/59) in the control group(P<0.05). CONCLUSIONS: Interactive scalp acupuncture could improve upper limb motor function and activities of daily living in patients with upper limb motor dysfunction after stroke.

GITRL impairs hepatocyte repopulation by liver progenitor cells to aggravate inflammation and fibrosis by GITR+CD8+ T lymphocytes in CDE Mice.

As an alternative pathway for liver regeneration, liver progenitor cells and their derived ductular reaction cells increase during the progression of many chronic liver diseases. However, the mechanism underlying their hepatocyte repopulation after liver injury remains unknown. Here, we conducted progenitor cell lineage tracing in mice and found that fewer than 2% of hepatocytes were derived from liver progenitor cells after 9 weeks of injury with a choline-deficient diet supplemented with ethionine (CDE), and this percentage increased approximately three-fold after 3 weeks of recovery. We also found that the proportion of liver progenitor cells double positive for the ligand of glucocorticoid-induced tumour necrosis factor receptor (GITRL, also called Tnfsf18) and SRY-related HMG box transcription 9 (Sox9) among nonparenchymal cells increased time-dependently upon CDE injury and reduced after recovery. When GITRL was conditionally knocked out from hepatic progenitor cells, its expression in nonparenchymal cells was downregulated by approximately fifty percent, and hepatocyte repopulation increased by approximately three folds. Simultaneously, conditional knockout of GITRL reduced the proportion of liver-infiltrating CD8+ T lymphocytes and glucocorticoid-induced tumour necrosis factor receptor (GITR)-positive CD8+ T lymphocytes. Mechanistically, GITRL stimulated cell proliferation but suppressed the differentiation of liver progenitor organoids into hepatocytes, and CD8+ T cells further reduced their hepatocyte differentiation by downregulating the Wnt/ß-catenin pathway. Therefore, GITRL expressed by liver progenitor cells impairs hepatocyte differentiation, thus hindering progenitor cell-mediated liver regeneration.

Targeting the JAK2/STAT3 signaling pathway with natural plants and phytochemical ingredients: A novel therapeutic method for combatting cardiovascular diseases.

The aim of this article is to introduce the roles and mechanisms of the JAK2/STAT3 pathway in various cardiovascular diseases, such as myocardial fibrosis, cardiac hypertrophy, atherosclerosis, myocardial infarction, and myocardial ischemiareperfusion. In addition, the effects of phytochemical ingredients and different natural plants, mainly traditional Chinese medicines, on the regulation of different cardiovascular diseases via the JAK2/STAT3 pathway are discussed. Surprisingly, the JAK2 pathway has dual roles in different cardiovascular diseases. Future research should focus on the dual regulatory effects of different phytochemical ingredients and natural plants on JAK2 to pave the way for their use in clinical trials.

Thalamic segmentation based on diffusion tensor imaging in patients with trigeminal neuralgia.

Classical trigeminal neuralgia (CTN) refers to episodic pain that is strictly confined to the trigeminal distribution area, and the thalamus is an important component of the trigeminal sensory pathway. Probabilistic tracking imaging algorithm was used to identify specific connections between the thalamus and the cortex, in order to identify structural changes in the thalamus of patients with CTN and perform thalamic segmentation. A total of 32 patients with CTN and 32 healthy controls underwent DTI-MRI scanning (3.0 T). Differences in fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) between the groups were studied. Correlation analysis was performed with clinical course and pain level. Compared to the healthy controls, patients in the CTN group had significantly reduced FA, increased AD, RD and MD in somatosensory subregion of the bilateral thalamus, increased RD in frontal subregion, increased RD and MD in motor subregion. Correlation analysis showed that patient history was positively correlated with pain grading, and that medical history was positively correlated with significantly reduced FA in somatosensory subregion, negatively correlated with increased RD and MD in motor subregion. We used DTI-based probabilistic fiber tracking to discover altered structural connectivity between the thalamus and cerebral cortex in patients with CTN and to obtain a thalamic segmentation atlas, which will help to further understand the pathophysiology of CTN and serve as a future reference for thalamic deep brain stimulation electrode implantation for the treatment of intractable pain.

Pharmacokinetic interactions between tacrolimus and Wuzhi capsule in liver transplant recipients: Genetic polymorphisms affect the drug interaction.

Wuzhi capsule (WZC), a commonly used Chinese patent medicine to treat various types of liver dysfunction in China, increases the exposure of tacrolimus (TAC) in liver transplant recipients. However, this interaction has inter-individual variability, and the underlying mechanism remains unclear. Current research indicates that CYP3A4/5 and drug transporters influence the disposal of both drugs. This study aims to evaluate the association between TAC dose-adjusted trough concentration (C/D) and specific genetic polymorphisms of CYP3A4/5, drug transporters and pregnane x receptor (PXR), and plasma levels of major WZC components, deoxyschisandrin and γ-schisandrin, in liver transplant patients receiving both TAC and WZC. Liquid chromatography-tandem-mass spectrometry was used to detect the plasma levels of deoxyschisandrin and γ-schisandrin, and nine polymorphisms related to metabolic enzymes, transporters and PXR were genotyped by sequencing. A linear mixed model was utilized to assess the impact of the interaction between genetic variations and WZC components on TAC lnC/D. Our results indicate a significant association of TAC lnC/D with the plasma levels of deoxyschisandrin and γ-schisandrin. Univariate analysis demonstrated three polymorphisms in the genes ABCB1 (rs2032582), ABCC2 (rs2273697), ABCC2 (rs3740066), and PXR (rs3842689) interact with both deoxyschisandrin and γ-schisandrin, influencing the TAC lnC/D. In multiple regression model analysis, the interactions between deoxyschisandrin and both ABCB1 (rs2032582) and ABCC2 (rs3740066), post-operative day (ß < 0.001, p < 0.001), proton pump inhibitor use (ß = -0.152, p = 0.008), body mass index (ß = 0.057, p < 0.001), and ABCC2 (rs717620, ß = -0.563, p = 0.041), were identified as significant factors of TAC lnC/D, accounting for 47.89% of the inter-individual variation. In summary, this study elucidates the influence of the interaction between ABCB1 and ABCC2 polymorphisms with WZC on TAC lnC/D. These findings offer a scientific basis for their clinical interaction, potentially aiding in the individualized management of TAC therapy in liver transplant patients.

Ginsenoside Rb1 prevents age-related endothelial senescence by modulating SIRT1/caveolin-1/enos signaling pathway.

Background: Advancing age is one of the independent risk factors for cardiovascular disorders. The Compendium of Materia Medica, a classic book on traditional Chinese medicine, states that ginseng "harmonizes the five internal organs, calming the spirit and prolonging the years of life." Considered one of the primary bioactive compounds derived from Panax ginseng, ginsenoside Rb1 (g-Rb1) has been scientifically suggested to possess anti-senescence efficacy. More research is needed to explore the vascular pharmacological activity and potential clinical application value of g-Rb1. Aims of the study: Our previous study demonstrated that g-Rb1 could mitigate cellular senescence via the SIRT1/eNOS pathway. This study was performed to explore the exact mechanisms by which g-Rb1 modulates the SIRT1/eNOS pathway. Materials and methods: We used human primary umbilical vein endothelial cells (HUVECs) to establish a replicative ageing model. Real-time (RT‒PCR), western blotting, small interfering RNA (siRNA), and immunoprecipitation were conducted to detect the effect of g-Rb1 on the SIRT1/caveolin-1/eNOS axis. Results: G-Rb1 increased NO production and alleviated replicative senescence of HUVECs. The application of g-Rb1 elevated the mRNA and protein abundance of both SIRT1 and eNOS while concomitantly suppressing the expression of caveolin-1. Inhibition of SIRT1 and eNOS by siRNAs suppressed the anti-senescence function of g-Rb1, while caveolin-1 siRNA could enhance it. G-Rb1 decreased the acetylation level of caveolin-1 and increased NO production, which was suppressed by SIRT1 siRNA. Both g-Rb1 and caveolin-1 siRNA could reduce the acetylation level of eNOS and increase NO production. Conclusion: G-Rb1 prevents age-related endothelial senescence by modulating the SIRT1/caveolin-1/eNOS signaling pathway.

Fufang Luohanguo Qingfei granules reduces influenza virus susceptibility via MAVS-dependent type I interferon antiviral signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Luohanguo Qingfei granules (LQG) is a Chinese patent medicine, clinically used to treat flu-like symptoms including cough with yellow phlegm, impeded phlegm, dry throat and tongue. However, the protective activity of LQG against influenza infection is indeterminate. AIM OF THE STUDY: This study is to investigate the therapeutic effect of LQG on influenza infection and elucidate its underlying mechanism. MATERIALS AND METHODS: In vivo: A viral susceptible mouse model induced by restraint stress was established to investigate LQG's beneficial effects on influenza susceptibility. MAVS knockout (Mavs-/-) mice were used to verify the potential mechanism of LQG. In vitro: Corticosteroid (CORT)-treated A549 cells were employed to identify the active ingredients in LQG. Mice morbidity and mortality were monitored daily for 21 days. Histopathologic changes and inflammatory cytokines in lung tissues were examined by H&E staining and ELISA. RNA-seq was used to explore the signaling pathway influenced by LQG and further confirmed by qPCR. Immunoblotting and immunohistochemistry (IHC) were used to determine the protein levels. CO-IP and DARTS were applied to detect protein-protein interaction and compound-protein interaction, respectively. RESULTS: LQG effectively attenuated the susceptibility of restrained mice to H1N1 infection. LQG significantly boosted the production of IFN-ß transduced by mitochondrial antiviral-signaling protein (MAVS), while MAVS deficiency abrogated its protective effects on restrained mice infected with H1N1. Moreover, in vitro studies further revealed that mogroside Ⅱ B, amygdalin, and luteolin are potentially active components of LQG. CONCLUSION: These results suggested that LQG inhibited the mitofusin 2 (Mfn2)-mediated ubiquitination of MAVS by impeding the E3 ligase synoviolin 1 (SYVN1) recruitment, thereby enhancing IFN-ß antiviral response. Overall, our work elaborates a potential regimen for influenza treatment through reduction of stress-induced susceptibility.