BDNF mimetics recover palmitic acid-induced injury in cardiomyocytes by ameliorating Akt-dependent mitochondrial impairments.

Cardiac lipotoxicity is a prevalent consequence of lipid metabolism disorders occurring in cardiomyocytes, which in turn precipitates the onset of heart failure. Mimetics of brain-derived neurotrophic factor (BDNF), such as 7,8-dihydroxyflavone (DHF) and 7,8,3'-trihydroxyflavone (THF), have demonstrated significant cardioprotective effects. However, it remains unclear whether these mimetics can protect cardiomyocytes against lipotoxicity. The aim of this study was to examine the impact of DHF and THF on the lipotoxic effects induced by palmitic acid (PA), as well as the concurrent mitochondrial dysfunction. H9c2 cells were subjected to treatment with PA alone or in conjunction with DHF or THF. Various factors such as cell viability, lactate dehydrogenase (LDH) release, death ratio, and mitochondrial function including mitochondrial membrane potential (MMP), mitochondrial-derived reactive oxygen species (mito-SOX) production, and mitochondrial respiration were assessed. PA dose-dependently reduced cell viability, which was restored by DHF or THF. Additionally, both DHF and THF decreased LDH content, death ratio, and mito-SOX production, while increasing MMP and regulating mitochondrial oxidative phosphorylation in cardiomyocytes. Moreover, DHF and THF specifically activated Akt signaling. The protective effects of DHF and THF were abolished when an Akt inhibitor was used. In conclusion, BDNF mimetics attenuate PA-induced injury in cardiomyocytes by alleviating mitochondrial impairments through the activation of Akt signaling.

Metabolomic analysis reveals macrophage metabolic reprogramming and polarization under different nutritional cues.

BACKGROUND AND AIMS: Obesity-induced chronic inflammation and metabolic abnormalities are highly relevant to the functional dysregulation of macrophages, especially under obese conditions. Hyperglycemia and hyperlipidemia, central to obesity, directly alter macrophage activity. However, the impacts of different nutritional cues on the intricate metabolic networks in macrophages remain unclear. MATERIALS AND METHODS: In this study, we employed metabolomic approaches to examine the metabolic responses of macrophages to high glucose, high fat and their coexistence, aiming to delineate the molecular mechanisms of nutritional factors on macrophage activation and obesity-related diseases from a metabolic perspective. RESULTS: Our findings revealed that different nutritional conditions could reprogram key metabolism in macrophages. Additionally, we identified a metabolite derived from macrophages, Long-Chain Phosphatidylcholine (LPC), which exerts beneficial effects on obese mice. It ameliorates the obesity phenotype and improves glucose metabolism profiles. This discovery suggests that LPC has a significant therapeutic potential in the context of obesity-induced metabolic dysfunctions. Our study unveils the metabolic phenotype of macrophages in high-fat and high-sugar environments and uncovers a macrophage-derived metabolite that significantly ameliorates the obesity phenotype. CONCLUSION: This finding reveals a potential dialogue mechanism between macrophages and adipocytes, shedding light on the complex interplay of immune and metabolic systems in obesity. This discovery not only enhances our understanding of obesity's underlying mechanisms but also opens up new avenues for therapeutic interventions targeting macrophage-adipocyte interactions.

Anti-adipogenesis effect of indole-3-acrylic acid on human preadipocytes and HFD-induced zebrafish.

BACKGROUND: Obesity, defined as excessive or abnormal body fat accumulation, which could significantly increase the risk of cardiovascular disease, type 2 diabetes mellitus (T2DM) diseases and seriously affect people's quality of life. More than 2 billion people are overweight, and the incidence of obesity is increasing rapidly worldwide, it has become a widely concerned public health issue in the world. Diverse evidence show that active metabolites are involved in the pathophysiological processes of obesity. AIMS: However, whether the downstream catabolite of tryptophan, 3-indole acrylic acid (IA), is involved in obesity remains unclear. METHODS: We collected the samples of serum from peripheral blood of obesity and health controls, and liquid chromatography-mass spectrometry (LC-MS) was performed to identify the plasma levels of IA. Additionally, we verified the potential benefits of IA on human preadipocytes and HFD- induced zebrafish by cell viability assay, flow cytometry assay, Oil red O staining, total cholesterol (T-CHO), triglyceride (TG) and nonesterified free fatty acids (NEFA) measurements and Nile Red staining. RNA-Seq, functional analysis and western blot revealed the mechanisms underlying the function of IA. RESULTS: We found that the content of IA in peripheral blood serum of overweight people was significantly lower than that of normal people. In addition, supplementation with IA in zebrafish larvae induced by a high fat diet (HFD) dramatically reduced HFD induced lipid accumulation. IA had no effect on proliferation and apoptosis of preadipocytes, but significantly inhibited adipogenesis of preadipocytes by down-regulate CEBPα and PPARγ. RNA-Seq and functional analysis revealed that IA regulated the adipogenesis of preadipocytes through stimulate the phosphorylation of STAT1. CONCLUSIONS: Taken together, IA has been identified as a potent metabolite for the prevention or treatment of obesity.

Taohong Siwu decoction ameliorates atherosclerosis in rats possibly through toll-like receptor 4/myeloid differentiation primary response protein 88/nuclear factor-κB signal pathway.

OBJECTIVE: To investigate the effect of Taohong Siwu decoction (, TSD) on atherosclerosis in rats as well as investigate the underlying mechanism based on molecular docking. METHODS: Sixty healthy male Sprague-Dawley rats were randomly divided into 6 groups with 10 rats in each group: control group, model group, atorvastatin group (AT, 2.0 mg/kg), and TSD groups (20, 10, 5 g/kg) after 7 d of acclimation. The model of atherosclerosis was successfully established except the control group by high fat diet (HFD) and vitamin D2. Biochemical analyzers were used to detect the levels of triglyceride (TG), total cholestero (TC), low density lipoprotein-cholesterol (LDL-C) and high density lipid-cholesterol (HDL-C) in blood lipid. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) were determined by enzyme-linked immunosorbent assay. Sudan IV staining and Hematoxylin and eosin staining (HE staining) were performed to observe the pathological changes in aortic tissue. Molecular docking technology was used to predict the best matching between the main components of TSD and the target proteins. The expression of target proteins was further detected by quantitative real time polymerase chain reaction (qRT-PCR) and Western blot analysis. RESULTS: The results showed that TSD restricted atherosclerosis development and decreased the inflammatory cytokines in plasma. Molecular docking results predicted that the main components of TSD showed a strong binding ability with toll-like receptor (TLR4), myeloid differentiation primary response protein 88 (MyD88), and nuclear factor kappa-B (NF-κB). The results of qRT-PCR and Western blot analysis showed that the mRNA and protein expressions of TLR4, MyD88 and NF-κB p65 in the aorta were reduced in atorvastatin group and TSD group. CONCLUSIONS: TSD can ameliorate atherosclerosis in rats, and the underlying mechanism is supposed be related to the suppression of inflammatory response by regulating TLR4/MyD88/NF-κB signal pathway.

Effects and mechanism of polysaccharides from Hedyotis diffusa on isoniazid-induced liver injury / 中国药房

OBJECTIVE To investigate the effects and mechanism of polysaccharides from Hedyotis diffusa （HDP） on isoniazid （INH）-induced liver injury. METHODS Healthy transgenic zebrafish with liver-specific fluorescence were divided into normal group， model group （4 mmol/L INH）， HDP low-concentration group （4 mmol/L INH+50 mg/mL HDP） and HDP high- concentration group （4 mmol/L INH+100 mg/mL HDP）. After grouping treating， the liver fluorescence area， fluorescence intensity and pathological changes of liver tissue were observed. Human liver L02 cells were divided into normal group， model group （4 mmol/L INH）， HDP low-concentration group （4 mmol/L INH+2 mg/mL HDP）， and HDP high-concentration group （4 mmol/L INH + 4 mg/mL HDP）. After grouping treating， the cell viability was detected， and the levels of alanine transaminase （ALT）， aspartate transaminase （AST）， and the content of glutathione （GSH） as well as the expression levels of silent information regulator 1 （Sirt1）， nuclear factor-erythroid 2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1） and quinone oxidoreductase 1 （NQO1） proteins were detected. RESULTS Compared with the model group， the HDP low- and high-concentration groups showed varying degrees of increase in the fluorescence area and fluorescence intensity （except for HDP low-concentration group） of zebrafish liver （P＜0.05 or P＜0.01）， and the characteristics of liver injury and necrosis had been improved to varying degrees. Compared with model group， the survival rate of L02 cells， the content of GSH （except for HDP low-concentration group）， the protein expression levels of Sirt1 （except for HDP low-concentration group）， Nrf2， NQO1， HO-1 （except for HDP low-concentration group） were significantly increased in HDP low- and high-concentration groups （P＜0.05 or P＜0.01）， and the levels of ALT and AST （except for HDP low-concentration group） were significantly decreased （P＜0.05）； the number of survival cells significantly increased， while the number of damaged or dead cells significantly decreased. CONCLUSIONS HDP has a potential protective effect against INH-induced liver injury， the mechanism of which may be associated with activating Sirt1/Nrf2 signaling pathway， improving mitochondrial function and enhancing antioxidant capacity.

Effect of Linggui Zhugantang on Mitochondrial Fusion-fission and Sirt3/ AMPK Signaling Pathway in Chronic Heart Failure Rats After Myocardial Infarction / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Linggui Zhugantang on mitochondrial fission and fusion and silencing information regulator 3（Sirt3）/adenosine monophosphate dependent protein kinase （AMPK） signaling pathway in chronic heart failure （CHF） rats after myocardial infarction （MI）. MethodSD rats randomly divide into sham operation group （normal saline ，thread only without ligature）， model group （normal saline， ligation of the left anterior descending coronary artery proximal to the heart）， Linggui Zhugantang group （4.8 g·kg-1） and Captopril group （0.002 57 g·kg-1）， with 10 rats in each group. Administere drug continuously for 28 days. Echocardiography detected cardiac function parameters. Hematoxylin eosin （HE） staining observed the pathological changes of the heart. Immunofluorescence detected the levels of reactive oxygen species （ROS）. JC-1 detect mitochondrial membrane potential. Colorimetry measure adenosine triphosphate （ATP）， superoxide dismutase （SOD）， malondialdehyde （MDA）， mitochondrial respiratory chain complex activity （Ⅰ-Ⅳ）. TdT-mediated dUTP nick end labeling （TUNEL） staining detected the apoptosis rate of myocardial tissue. Western blot detected protein expression levels of Sirt3， phosphorylated AMPK （p-AMPK）， phosphorylated dynamic-related protein 1（p-Drp1）， mitochondrial fission protein 1（Fis1）， mitochondrial fission factor （MFF）， optic atrophy protein 1（OPA1）. ResultCompared to the sham group， the left ventricular end diastolic diameter （LVIDd） and left ventricular end systolic diameter （LVIDs） were significantly increased in model group （P<0.01）， while the left ventricular short axis shortening rate （LVFS） and left ventricular ejection fraction （LVEF） were significantly decreased （P<0.01）. There were inflammatory cell infiltration and obvious pathological injury in myocardial tissue. ROS， MDA levels and myocardial cell apoptosis rate were significantly increased （P<0.01）， SOD level， ATP content， and membrane potential were significantly decreased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） was significantly decreased （P<0.01）. Levels of p-Drp1， Fis1， MFF proteins were significantly up-regulated （P<0.01）， while Sirt3， p-AMPK， OPA1 proteins level were significantly down-regulated （P<0.01）. Compared with model group， LVIDd and LVIDs were significantly decreased （P<0.01）， LVEF and LVFS were significantly increased （P<0.01）. Inflammatory cell infiltration and pathological damage of myocardial tissue were significantly relieved. ROS， MDA levels and myocardial cell apoptosis rate were significantly decreased in Linggui Zhugantang group and Captopril group （P<0.01）， SOD level， ATP content， and membrane potential significantly increased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） increased significantly （P<0.01），and p-Drp1， Fis1， MFF protein levels were significantly down-regulated （P<0.01）， Sirt3， p-AMPK， OPA1 protein were significantly up-regulated （P<0.01）. ConclusionLinggui Zhugantang can alleviate oxidative stress and apoptosis damage of myocardial cells， maintain mitochondrial function stability， and its effect may be related to mitochondrial mitosis fusion and Sirt3/AMPK signaling pathway.

Transcriptomics profiling reveal the heterogeneity of white and brown adipocyte.

The marker genes associated with white adipocytes and brown adipocytes have been previously identified; however, these markers have not been updated in several years, and the differentiation process of preadipocytes remains relatively fixed. Consequently, there has been a lack of exploration into alternative differentiation schemes. In this particular study, we present a transcriptional signature specific to brown adipocytes and white adipocytes. Notably, our findings reveal that ZNF497, ZIC1, ZFY, UTY, USP9Y, TXLNGY, TTTY14, TNNT3, TNNT2, TNNT1, TNNI1, TNNC1, TDRD15, SOX11, SLN, SFRP2, PRKY, PAX3KLHL40, PAX3, INKA2-AS1, SOX11, and TDRD15 exhibit high expression levels in brown adipocytes. XIST, HOXA10, PCAT19, HOXA7, PLSCR3, and AVPR1A exhibited high expression levels in white adipocytes, suggesting their potential as novel marker genes for the transition from white to brown adipocytes. Furthermore, our analysis revealed the coordinated activation of several pathways, including the PPAR signaling pathway, focal adhesion, retrograde endocannabinoid signaling, oxidative phosphorylation, PI3K-Akt signaling pathway, and thermogenesis pathways, in brown adipocytes. Moreover, in contrast to prevailing culture techniques, we conducted a comparative analysis of the differentiation protocols for white preadipocytes and brown preadipocytes, revealing that the differentiation outcome remained unaffected by the diverse culture schemes employed. However, the expression levels of certain marker genes in both adipocyte types were found to be altered. This investigation not only identified potential novel marker genes for adipocytes but also examined the impact of different differentiation methods on preadipocyte maturation. Consequently, these findings offer significant insights for further research on the differentiation processes of diverse adipocyte subtypes.

Traumatic acid inhibits ACSL4 associated lipid accumulation in adipocytes to attenuate high-fat diet-induced obesity.

Obesity is a major health concern that lacks effective intervention strategies. Traumatic acid (TA) is a potent wound-healing agent in plants, considered an antioxidant food ingredient. This study demonstrated that TA treatment significantly reduced lipid accumulation in human adipocytes and prevented high-fat diet induced obesity in zebrafish. Transcriptome sequencing revealed TA-activated fatty acid (FA) degradation and FA metabolism signaling pathways. Moreover, western blotting and quantitative polymerase chain reaction showed that TA inhibited the expression of long-chain acyl-CoA synthetase-4 (ACSL4). Overexpression of ACSL4 resulted in the reversal of TA beneficiary effects, indicating that the attenuated lipid accumulation of TA was regulated by ACSL4 expression. Limited proteolysis-mass spectrometry and microscale thermophoresis were then used to confirm hexokinase 2 (HK2) as a direct molecular target of TA. Thus, we demonstrated the molecular basis of TA in regulating lipid accumulation and gave the first evidence that TA may function through the HK2-ACSL4 axis.

7,8,3'-Trihydroxyflavone prevents doxorubicin-induced cardiotoxicity and mitochondrial dysfunction via activating Akt signaling pathway in H9c2 cells.

Clinical application of the widely used chemotherapeutic agent, doxorubicin (DOX), is limited by its cardiotoxicity. Mitochondrial dysfunction has been revealed as a crucial factor in DOX-induced cardiotoxicity. 7,8,3'-Trihydroxyflavone (THF) is a mimetic brain-derived neurotrophic factor with neuroprotective effects. However, the potential effects of THF on DOX-induced cardiomyocyte damage and mitochondrial disorders remain unclear. H9c2 cardiomyoblasts were exposed to DOX and/or THF at different concentrations. Cardiomyocyte injury was evaluated using lactate dehydrogenase (LDH) assay and Live/Dead cytotoxicity kit. Meanwhile, mitochondrial membrane potential (MMP), morphology, mitochondrial reactive oxygen species (mito-ROS) production, and the oxygen consumption rate of cardiomyocytes were measured. The protein levels of key mitochondria-related factors such as adenosine monophosphate-activated protein kinase (AMPK), mitofusin 2 (Mfn2), dynamin-related protein 1 (Drp1), and optic atrophy protein 1 (OPA1) were examined. We found that THF reduced LDH content and death ratio of DOX-treated cardiomyocytes in a concentration-dependent manner, while increasing MMP without significantly affecting the routine and maximum capacity of mitochondrial respiration. Mechanistically, THF increased the activity of Akt and protein levels of Mfn2 and heme oxygenase 1 (HO-1). Moreover, inhibition of Akt reversed the protective role of THF, increased mito-ROS levels, and repressed Mfn2 and HO-1 expression. Therefore, we conclude, THF relieves DOX-induced cardiotoxicity and improves mitochondrial function by activating Akt-mediated Mfn2 and HO-1 pathways. This finding provides promising therapeutic insights for DOX-induced cardiac dysfunction.

Brown adipocyte activation mediates lipid metabolism through exosomal tRNA-derived fragments.

Human obesity is related with intrinsic impairments of adipocyte lipolysis and ectopic lipid accumulation. Small regulatory RNAs, such as tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs), are enriched in exosomes and play a crucial role in lipid metabolism. To determine certain tRFs for lipolysis, brown adipocytes were treated with forskolin. Using tRFs sequencing, 207 different expressed exosomal tRFs were determined. In forskolin samples, 145 downregulated and 62 upregulated tRFs were identified. Further, qRT-PCR validated that three notably upregulated tRFs (tRF-Gly-GCC-007, tRF-Gly-GCC-008, and tRF-Gly-GCC-009) were in accordance with the sequencing result. Target genes of tRFs were involved in positive regulation of protein phosphorylation and cell adhesion process by significantly downregulating UCHL1 expression, which might participate in lipolysis. This study might provide therapeutic targets and potential diagnostic biomarkers for obesity treatment.

BDNF mimetic 7,8-dihydroxyflavone rescues rotenone-induced cytotoxicity in cardiomyocytes by ameliorating mitochondrial dysfunction.

The relationship between mitochondrial dysfunction and cardiovascular disease pathogenesis is well recognized. 7,8-Dihydroxyflavone (7,8-DHF), a mimetic of brain-derived neurotrophic factor, inhibits mitochondrial impairments and improves cardiac function. However, the regulatory role of 7,8-DHF in the mitochondrial function of cardiomyocytes is not fully understood. To investigate the potential mito-protective effects of 7,8-DHF in cardiomyocytes, we treated H9c2 or HL-1 cells with the mitochondrial respiratory complex I inhibitor rotenone (Rot) as an in vitro model of mitochondrial dysfunction. We found that 7,8-DHF effectively eliminated various concentrations of Rot-induced cell death and reduced lactate dehydrogenase release. 7,8-DHF significantly improved mitochondrial membrane potential and inhibited mitochondrial reactive oxygen species. Moreover, 7,8-DHF decreased routine and leak respiration, restored protein levels of mitochondrial complex I-IV, and increased ATP production in Rot-treated H9c2 cells. The protective role of 7,8-DHF in Rot-induced damage was validated in HL-1 cells. Nuclear phosphorylation protein expression of signal transducer and activator of transcription 3 (STAT3) was significantly increased by 7,8-DHF. The present study suggests that 7,8-DHF rescues Rot-induced cytotoxicity by inhibiting mitochondrial dysfunction and promoting nuclear translocation of p-STAT3 in cardiomyocytes, thus nominating 7,8-DHF as a new pharmacological candidate agent against mitochondrial dysfunction in cardiac diseases.

Combining mechanisms of black carbon and magnetic minerals in power plant fly ash.

Black carbon (BC), one of the pollutants emitted from fossil fuel combustion, is closely associated with minerals and other hazardous substances. To date, little is known about the mechanisms between BC and magnetic minerals. Accordingly, further investigating the association between magnetic minerals and BC is necessary. In this work, the extraction of BC from fly ash and the magnetic fraction from BC was achieved by flotation and magnetic separation, respectively. The morphology, mineralogical composition, and magnetic properties of BC and magnetic fraction were characterized by FTIR, XRD, SEM-EDS, and vibrating sample magnetometer (VSM). The results show that BC and magnetic minerals have similar mineral compositions, rich in quartz, mullite, magnetite, and hematite. The magnetic minerals have prominent spherical characteristics and are distributed on the surface and inside the pores of BC with irregular honeycomb features. The VSM and XRD analyses show that Fe3O4 is the primary magnetic material. Moreover, large amounts of C, O, and Fe around and on the surface of magnetic spheres were detected by EDS, indicating that the spherical particles may be the structure of BC-coated Fe3O4. Pyrolysis experiments showed that the yield of the magnetic fraction in the pyrolysis product reached 60 %, far exceeding the theoretical yield of 12 % based on 5 % of doped Fe. This further proves that Fe3O4 was combined with a large number of organics during its formation, which may be due to coating and chemical adsorption. Quantum chemical calculations also confirmed this chemical adsorption between Fe3O4 with BC based on density flooding theory, in which adsorption energies ranged from -213.374 KJ/mol to -827.741 KJ/mol.

7,8-Dihydroxyflavone alleviates cardiac fibrosis by restoring circadian signals via downregulating Bmal1/Akt pathway.

Brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) pathway is a therapeutic target in cardiac diseases. A BDNF mimetic, 7,8-dihydroxyflavone (7,8-DHF), is emerging as a protective agent in cardiomyocytes; however, its potential role in cardiac fibroblasts (CFs) and fibrosis remains unknown. Thus, we aimed to explore the effects of 7,8-DHF on cardiac fibrosis and the possible mechanisms. Myocardial ischemia (MI) and transforming growth factor-ß1 (TGF-ß1) were used to establish models of cardiac fibrosis. Hematoxylin & eosin and Masson's trichrome stains were used for histological analysis and determination of collagen content in mouse myocardium. Cell viability kit, EdU (5-ethynyl-2'-deoxyuridine) assay and immunofluorescent stain were employed to examine the effects of 7,8-DHF on the proliferation and collagen production of CFs. The levels of collagen I, α-smooth muscle actin (α-SMA), TGF-ß1, Smad2/3, and Akt as well as circadian rhythm-related signals including brain and muscle Arnt-like protein 1 (Bmal1), period 2 (Per2), and cryptochrome 2 (Cry2) were analyzed. Treatment with 7,8-DHF markedly alleviated cardiac fibrosis in MI mice. It inhibited the activity of CFs accompanied by decreasing number of EdU-positive cells and downregulation of collagen I, α-SMA, TGF-ß1, and phosphorylation of Smad2/3. 7,8-DHF significantly restored the dysregulation of Bmal1, Per2, and Cry2, but inhibited the overactive Akt. Further, inhibition of Bmal1 by SR9009 effectively attenuated CFs proliferation and collagen production of CFs. In summary, these findings indicate that 7,8-DHF attenuates cardiac fibrosis and regulates circadian rhythmic signals, at least partly, by inhibiting Bmal1/Akt pathway, which may provide new insights into therapeutic cardiac remodeling.

Methionine sulfoxide suppresses adipogenic differentiation by regulating the mitogen-activated protein kinase signaling pathway.

In this study, methionine sulfoxide (MetO) was identified as an active metabolite that suppresses adipogenesis after screening obese individuals versus the normal population. MetO suppressed the gene and protein expression of CCAAT/enhancer binding protein (C/EBP) α, adipocyte fatty acid binding protein 4 (FABP4), and the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) during human preadipocyte (HPA) differentiation. Adipogenesis decreased following MetO treatment; however, the preadipocyte number, proliferation, and apoptosis were unaffected. The activity of phosphorylated extracellular signal-related kinase (P-ERK) of the mitogen-activated protein kinase (MAPK) pathway was significantly inhibited in HPA after MetO treatment. Furthermore, treatment of preadipocytes with the selective P-ERK1/2 agonist Ro 67-7476 abolished the effect of MetO against adipogenesis suggesting that MetO function is dependent on the MAPK pathway. The mechanistic insights of adipogenesis suppression by MetO presented in this study shows its potential as an antiobesity drug.

A Retrospective Study on the Characteristics of Traditional Chinese Medical Syndromes in 3088 Cases of Atherosclerotic Cerebral Infarction / 中医杂志

ObjectiveTo investigate the characteristics of traditional Chinese medicine syndrome and the evolution of pathogenesis in different stages of atherosclerotic thrombotic cerebral infarction （ATCI）. MethodsClinical data of 3088 ATCI patients from 8 hospitals in 6 provinces and cities were collected from the hospital information system during January 1， 2015 to December 31， 2019. After staging and counting clinical symptoms， common factors were extracted using the principal component analysis method in factor analysis. Cluster analysis was then carried out on the basis of the factor analysis. The results of the combination of the evidence element identification， cluster analysis and expert discussion were used to discuss the evidence of the different disease stages of atherosclerotic cerebral infarction. ResultsOf the 3088 ATCI patients included， 2290 cases were in the acute phase and 798 in the non-acute phase. Excluding the main symptoms of ischaemic stroke， such as numbness and weakness of limbs， unfavourable movement， unfavourable speech and dizziness， we identified 84 indicators with a frequency ≥5% of the four diagnostic information variables. Of these， 36 indicators were observed in the acute phase and 35 in the non-acute phase. Factor analysis extracted 14 common factors from each phase. We selected factors with a loading coefficient ＞0.3 for evidence determination. These 14 groups of common factors were used as variables for clustering. After clustering， the acute， non-acute phase were each divided into 5 categories. Based on a combination of clinical practice and expert opinion， the symptoms identified in the acute period were syndrome of deficiency of both qi and yin， syndrome of blockade of wind-phlegm-static blood （36.07%）， syndrome of qi deficiency and blood stasis （20.74%）， syndrome of upward disturbance of wind-fire （15.15%）， syndrome of stirring wind due to yin deficiency （9.43%）， and syndrome of spleen deficiency and liver hyperactivity （3.80%）. In the non-acute phase， the symptoms were qi and yin deficiency with syndrome of qi stagnation and blood stasis （45.49%）， syndrome of deficiency of both qi and yin （20.05%）， syndrome of qi stagnation and blood stasis （16.42%）， spleen-kidney deficiency syndrome （8.52%）， and syndrome of hyperactivity of liver yang （4.89%）. ConclusionThe acute phase of AICI is mainly characterized by blood stasis， fire， internal wind， hyperactivity of yang， qi deficiency and yin deficiency， while the non-acute phase is characterized by yin deficiency， qi deficiency， blood stasis and qi stagnation. The main pathomechanism of ATCI involves deficiency of qi and yin， as well as obstruction of the channels by phlegm and blood stasis， and the fundamental pathomechanism is deficiency of qi and yin.

Clinical application study of parathyroid autofluorescence in identification of parathyroid gland in thyroid carcinoma surgery / 中华内分泌外科杂志

Objective:To observe the application of near-infrared autofluorescence imaging (NIRAF) technology combined with carbon nanoparticle (CNP) negative imaging in identification of parathyroid gland (PG) during thyroid carcinoma surgery.Methods:80 patients with thyroid cancer who underwent total thyroidectomy + central lymph node dissection performed by the same experienced physician team at the 960th Hospital of the PLA from Jan. to Mar. 2022 were prospectively included. Before operation, they were divided into two groups using random number table method before surgery: control group (40 cases) using CNP negative imaging, and experimental group (40 cases) using CNP negative imaging combined with NIRAF technique for intraoperative identification of PG. The gold standard for the identification of parathyroid glands was to compare the amount of intraoperative discovery retention misresection and transplantation of PG and the number of postoperative parathyroid hormone (PTH) and the number of complications in the two groups by immune colloidal gold technique. SPSS 25.0 software was used for statistical analysis.Results:All patients in the two groups were successfully operated and followed up. 137 149 PG were found and confirmed in the control group and the observation group, 108 132 PG were retained in situ and 29 17 PG were transplanted, the differences were statistically significant (all P <0.05) ; The number of A1 PG was 103 and 109, respectively. Among them, 84 102 were retained in situ and 19 7 were transplanted, the difference was statistically significant ( P <0.05) . There was no significant difference in the amount of A2 type PG and B type PG between the two groups ( P >0.05) . No A3 type PG was found in the two groups, and a total of 3 A3 types of PG were confirmed in postoperative pathological reports. There were no significant differences in misresection in the control group and the observation group, 5 and 2 PG were mistakenly cut, respectively (all P >0.05) . The PTH 1 day after surgery was 17.7 (5.6,30.4) pg/mL in the control group and 21.7 (12.8,38.3) pg/mL in the observation group, the difference was statistically significant ( P<0.05) . There were no significant differences in the levels of serum calcium and serum phosphorus 1 day after operation and PTH 1 month after surgery between the two groups (all P > 0.05) . Conclusion:Compared with CNP alone, combined with NIRAF technique can quickly and effectively identify PG, and PG can be better protected in situ and postoperative hypoparathyroidism can be reduced.

Effect of Shugan Tiaoshen acupuncture combined with western medication on depression-insomnia comorbidity due to COVID-19 quarantine: a multi-central randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of Shugan Tiaoshen acupuncture (acupuncture for soothing the liver and regulating the mentality) combined with western medication on depression and sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, and investigate the potential mechanism from the perspective of cortical excitability.@*METHODS@#Sixty patients with depression-insomnia comorbidity due to COVID-19 quarantine were randomly divided into an acupuncture group and a sham-acupuncture group, 30 cases in each one. The patients of both groups were treated with oral administration of sertraline hydrochloride tablets. In the acupuncture group, Shugan Tiaoshen acupuncture was supplemented. Body acupuncture was applied to Yintang (GV 24+), Baihui (GV 20), Hegu (LI 4), Zhaohai (KI 6), Qihai (CV 6), etc. The intradermal needling was used at Xin (CO15), Gan (CO12) and Shen (CO10). In the sham-acupuncture group, the sham-acupuncture was given at the same points as the acupuncture group. The compensatory treatment was provided at the end of follow-up for the patients in the sham-acupuncture group. In both groups, the treatment was given once every two days, 3 times a week, for consecutive 8 weeks. The self-rating depression scale (SDS) and insomnia severity index (ISI) scores were compared between the two groups before and after treatment and 1 month after the end of treatment (follow-up) separately. The cortical excitability indexes (resting motor threshold [rMT], motor evoked potential amplitude [MEP-A], cortical resting period [CSP]) and the level of serum 5-hydroxytryptamine (5-HT) were measured before and after treatment in the two groups.@*RESULTS@#After treatment and in follow-up, SDS and ISI scores were decreased in both groups compared with those before treatment (P<0.05), and the scores in the acupuncture group were lower than those in the sham-acupuncture group (P<0.05), and the decrease range in the acupuncture group after treatment was larger than that in the sham-acupuncture group (P<0.05). After treatment, rMT was reduced (P<0.05), while MEP-A and CSP were increased (P<0.05) in the acupuncture group compared with that before treatment. The levels of serum 5-HT in both groups were increased compared with those before treatment (P<0.05). The rMT in the acupuncture group was lower than that in the sham-acupuncture group, while MEP-A and CSP, as well as the level of serum 5-HT were higher in the acupuncture group in comparison with the sham-acupuncture group (P<0.05).@*CONCLUSION@#Shugan Tiaoshen acupuncture combined with western medication can relieve depression and improve sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, which is probably related to rectifying the imbalanced excitatory and inhibitory neuronal functions.

Lingnan Fire-needle on Inhibiting Melanocyte Apoptosis in Vitiligo Model Mice by Regulating Hippo-YAP Signaling Pathway / 中山大学学报(医学科学版)

ObjectiveTo observe the effects of fire-needle of Lingnan on the vitiligo model after hydroquinone-induced oxidative stress based on the Hippo-YAP signaling pathway. MethodsC57BL/6 mice were randomly divided into normal group （Control）， model group （HQ）， HQ+fire-needle group （FA）， and positive control group （Halometasone）， with 8 mice in each group. The vitiligo model was prepared by hydroquinone （HQ）. The skin pathological changes were observed by depigmentation score， HE staining and Masson-Fontana. Elisa was used to detect the levels of tyrosinase （TYR）， malondialdehyde （MDA） and monoamine oxidase （MAO）.Western-blot and PCR were used to detect the expression of Yap1 and Tp73 among the groups. ResultsCompared with the control group， the epidermis and dermis were significantly thicker. The number of melanocyte hair follicles， basal melanocytes， epidermal cells containing melanin granules were significantly decreased， and the depigmentation score was significantly reduced（P＜0.01）. The level of TYR decreased， and the levels of MDA and MAO increased after modeling（P＜0.01）. The expression of Yap1 and Tp73 were significantly reduced （P<0.01）. The dermis became thinner in the halometasone and FA group after treatment of 4 weeks. The number of melanocyte hair follicles， basal melanocytes， epidermal cells containing melanin granules increased （P<0.05）. Compared with that of the HQ group， the level of TYR in the halometasone group and FA group was significantly increased （P<0.01）. The levels of MDA and MAO in the FA group were decreased （P<0.05）. The expressions of Yap1 and Tp73 in the FA group were significantly increased （P<0.01）， and their effects were better than those in the Halometasone group （P<0.05）. ConclusionsFire-needle of Lingnan protects melanocytes from oxidative stress by activating the Hippo-YAP pathway. It enhances the synthesis and function of melanocytes and promotes repigmentation by reducing the content and activity of oxidative stress products.

Effects of activating mTORC2/Akt signaling pathway on dopaminergic neurons and behaviors in 6-hydroxydopamin model mice / 解剖学报

Objective To explore the effect of activation of mammalian target of rapmycin complex 2(mTORC2)/Akt signaling pathway on dopaminergic neurons and behavior in 6-hydroxydopamine (6-OHDA) model mice and its possible mechanism. Methods Selecting 36 mice which The Nestin-CreERTM and ROSA26-LacZ reporter genes were detected at the same time in 3-month-old male C57BL/6J mice weighing 20-25 g divideng them into 4 gruops, NS+ corn oil group, 6-OHDA+corn oil group, 6-OHDA+PP242 group and 6-OHDA+A-443654 group, and 6-OHDA was injected into the right striatum of the brain to replicate the Parkinson’s disease (PD) model of mice, and then daily intraperitoneal injection of mTORC2/Akt signaling pathway agonist A-443654 or inhibitor PP242. Serum interleukin-1β (IL-1β) and tumor necrosis factor-α(TNF-α)levels were measured by enzyme-linked immunosorbent assay. Immunohistochemistry and immunofluorescence staining were performed to investigate the change of microglia, dopaminergic neurons as well as neural progenitor cells (NPCs). Western blotting was used to detect the expression of related protein of mTORC2/Akt signaling pathway including rictor, p-Akt and regulated in development and DNA dgmage responses 1(REDD1) and the interaction between them were verified by immunoprecipitation. Finally, the behavioral performance of each group of mice was observed. Results With the activation of microglia and the increase of inflammatory factors in PD model mice, the number of dopaminergic neurons in the substantia nigra(SN) decreased significantly, and the motor function of the mice was impaired, but the number of NPCs increased significantly compared with the control mice, mTORC2/Akt signaling pathway related protein expression was also significantly up-regulated. A-443654 treatment further up-regulated the expression of these proteins, meanwhile the indicators mentioned above were ameliorated. However, the inhibitor PP242 treatment group showed completely opposite result with the agonist group. Conclusion A-443654 can promote the proliferation of NPCs and the number of new-born dopaminergic neurons by up-regulating related proteins of mTORC2/Akt signaling pathway, and reducing the activation of microglia and the level of inflammation factors, which ultimately lead to the amelioration of SN-striatal dopaminergic neurons and behavioral performance in PD model mice.