[Prescription and medication rules of traditional Chinese medicine for prevention and treatment of diabetic microangiopathy based on literature mining].

This study explored the prescription and medication rules of traditional Chinese medicine(TCM) in the prevention and treatment of diabetic microangiopathy based on literature mining. Relevant literature on TCM against diabetic microangiopathy was searched and prescriptions were collected. Microsoft Excel 2021 software was used to establish a prescription database, and an analysis was conducted on the frequency, properties, flavors, meridian tropism, and efficacy classifications of drugs. Association rule analysis, cluster analysis, and factor analysis were performed using SPSS Modeler 18.0 and SPSS Statistics 26.0 software. The characteristic active components and mechanisms of action of medium-high frequency drugs in the analysis of medication rules were explored through li-terature mining. A total of 1 327 prescriptions were included in this study, involving 411 drugs, with a total frequency reaching 19 154 times. The top five high-frequency drugs were Astragali Radix, Angelicae Sinensis Radix, Poria, Salviae Miltiorrhizae Radix et Rhizoma, and Rehmanniae Radix. The cold and warm drugs were used in combination. Drugs were mainly sweet, followed by bitter and pungent, and acted on the liver meridian. The majority of drugs were effective in tonifying deficiency, clearing heat, activating blood, and resolving stasis. Association rule analysis identified the highly supported drug pair of Astragali Radix-Angelicae Sinensis Radix and the highly confident drug combination of Poria-Alismatis Rhizoma-Corni Fructus. The strongest correlation was found among Astragali Radix, Angelicae Sinensis Radix, Poria, and Salviae Miltiorrhizae Radix et Rhizoma through the complex network analysis. Cluster analysis identified nine categories of drug combinations, while factor analysis identified 16 common factors. The analysis of active components in high-frequency drugs for the treatment of diabetic microangiopathy revealed that these effective components mainly exerted their effects by inhibiting oxidative stress and suppressing inflammatory reactions. The study found that the pathogenesis of diabetic microangiopathy was primarily characterized by deficiency in origin, with a combination of deficiency and excess. Deficiency was manifested as Qi deficiency and blood deficiency, while excess as phlegm-heat and blood stasis. The key organ involved in the pathological changes was the liver. The treatment mainly focused on supplementing Qi and nourishing blood, supplemented by clearing heat, coo-ling blood, activating blood, and dredging collaterals. Commonly used formulas included Danggui Buxue Decoction, Liuwei Dihuang Pills, Erzhi Pills, and Buyang Huanwu Decoction. The mechanisms of action of high-frequency drugs in the treatment of diabetic microangiopathy were often related to the inhibition of oxidative stress and suppression of inflammatory reactions. These findings can provide references for the clinical treatment of diabetic microangiopathy and the development of targeted drugs.

Sirtuin 3 deficiency exacerbates diabetic cardiomyopathy via necroptosis enhancement and NLRP3 activation.

Sirtuin 3 (SIRT3) is a potential therapeutic target for cardiovascular, metabolic, and other aging-related diseases. In this study, we investigated the role of SIRT3 in diabetic cardiomyopathy (DCM). Mice were injected with streptozotocin (STZ, 60 mg/kg, ip) to induce diabetes mellitus. Our proteomics analysis revealed that SIRT3 expression in the myocardium of diabetic mice was lower than that of control mice, as subsequently confirmed by real-time PCR and Western blotting. To explore the role of SIRT3 in DCM, SIRT3-knockout mice and 129S1/SvImJ wild-type mice were injected with STZ. We found that diabetic mice with SIRT3 deficiency exhibited aggravated cardiac dysfunction, increased lactate dehydrogenase (LDH) level in the serum, decreased adenosine triphosphate (ATP) level in the myocardium, exacerbated myocardial injury, and promoted myocardial reactive oxygen species (ROS) accumulation. Neonatal rat cardiomyocytes were transfected with SIRT3 siRNA, then exposed to high glucose (HG, 25.5 mM). We found that downregulation of SIRT3 further increased LDH release, decreased ATP level, suppressed the mitochondrial membrane potential, and elevated oxidative stress in HG-treated cardiomyocytes. SIRT3 deficiency further raised expression of necroptosis-related proteins including receptor-interacting protein kinase 1 (RIPK1), RIPK3, and cleaved caspase 3, and upregulated the expression of inflammation-related proteins including NLR family pyrin domain-containing protein 3 (NLRP3), caspase 1 p20, and interleukin-1ß both in vitro and in vivo. Collectively, SIRT3 deficiency aggravated hyperglycemia-induced mitochondrial damage, increased ROS accumulation, promoted necroptosis, possibly activated the NLRP3 inflammasome, and ultimately exacerbated DCM in the mice. These results suggest that SIRT3 can be a molecular intervention target for the prevention and treatment of DCM.

A novel Diels-Alder adduct of mulberry leaves exerts anticancer effect through autophagy-mediated cell death.

Guangsangon E (GSE) is a novel Diels-Alder adduct isolated from leaves of Morus alba L, a traditional Chinese medicine widely applied in respiratory diseases. It is reported that GSE has cytotoxic effect on cancer cells. In our research, we investigated its anticancer effect on respiratory cancer and revealed that GSE induces autophagy and apoptosis in lung and nasopharyngeal cancer cells. We first observed that GSE inhibits cell proliferation and induces apoptosis in A549 and CNE1 cells. Meanwhile, the upregulation of autophagosome marker LC3 and increased formation of GFP-LC3 puncta demonstrates the induction of autophagy in GSE-treated cells. Moreover, GSE increases the autophagy flux by enhancing lysosomal activity and the fusion of autophagosomes and lysosomes. Next, we investigated that endoplasmic reticulum (ER) stress is involved in autophagy induction by GSE. GSE activates the ER stress through reactive oxygen species (ROS) accumulation, which can be blocked by ROS scavenger NAC. Finally, inhibition of autophagy attenuates GSE-caused cell death, termed as "autophagy-mediated cell death." Taken together, we revealed the molecular mechanism of GSE against respiratory cancer, which demonstrates great potential of GSE in the treatment of representative cancer.

Dihydromyricetin Attenuates Myocardial Hypertrophy Induced by Transverse Aortic Constriction via Oxidative Stress Inhibition and SIRT3 Pathway Enhancement.

Dihydromyricetin (DMY), one of the flavonoids in vine tea, exerts several pharmacological actions. However, it is not clear whether DMY has a protective effect on pressure overload-induced myocardial hypertrophy. In the present study, male C57BL/6 mice aging 8⁻10 weeks were subjected to transverse aortic constriction (TAC) surgery after 2 weeks of DMY (250 mg/kg/day) intragastric administration. DMY was given for another 2 weeks after surgery. Blood pressure, myocardial structure, cardiomyocyte cross-sectional area, cardiac function, and cardiac index were observed. The level of oxidative stress in the myocardium was assessed with dihydroethidium staining. Our results showed that DMY had no significant effect on the blood pressure. DMY decreased inter ventricular septum and left ventricular posterior wall thickness, relative wall thickness, cardiomyocyte cross-sectional areas, as well as cardiac index after TAC. DMY pretreatment also significantly reduced arterial natriuretic peptide (ANP), brain natriuretic peptide (BNP) mRNA and protein expressions, decreased reactive oxygen species production and malondialdehyde (MDA) level, while increased total antioxidant capacity (T-AOC), activity of superoxide dismutase (SOD), expression of sirtuin 3 (SIRT3), forkhead-box-protein 3a (FOXO3a) and SOD2, and SIRT3 activity in the myocardium of mice after TAC. Taken together, DMY ameliorated TAC induced myocardial hypertrophy in mice related to oxidative stress inhibition and SIRT3 pathway enhancement.

Global trend and future landscape of intestinal microcirculation research from 2000 to 2021: A scientometric study.

BACKGROUND: The intestinal microcirculation functions in food absorption and metabolic substance exchanges. Accumulating evidence indicates that intestinal microcirculatory dysfunction is a significant source of multiple gastrointestinal diseases. To date, there has not been a scientometric analysis of intestinal microcirculatory research. AIM: To investigate the current status, development trends, and frontiers of intestinal microcirculatory research based on bibliometric analysis. METHODS: VOSviewer and CiteSpace 6.1.R2 were used to identify the overall characteristics and knowledge map of intestinal microcirculatory research based on the core literature published from 2000 to 2021 in the Web of Science database. The characteristics of each article, country of origin, institution, journal, cocitations, and other information were analyzed and visualized. RESULTS: There were 1364 publications enrolled in the bibliometric analysis, exhibiting an upward trend from 2000 to 2021 with increased participation worldwide. The United States and Dalhousie University took the lead among countries and institutions, respectively. Shock was the most prolific journal, and Nature Reviews Microbiology Clinical had the most citations. The topical hotspots and frontiers in intestinal microcirculatory research were centered on the pathological processes of functional impairment of intestinal microvessels, diverse intestinal illnesses, and clinical treatment. CONCLUSION: Our study highlights insights into trends of the published research on the intestinal microcirculation and offers serviceable guidance to researchers by summarizing the prolific areas in intestinal disease research to date.

Solid-state-cultured mycelium of Antrodia camphorata exerts potential neuroprotective activities against 6-hydroxydopamine-induced toxicity in PC12 cells.

Antrodia camphorata (A. camphorata) is an edible fungus containing various bioactive compounds generally used for health benefits. This study aimed to explore the potential neuroprotective activities of solid-state-cultured mycelium of A. camphorata (SCMAC) against Parkinson's disease (PD), as well as the underlying mechanism using an in vitro 6-hydroxydopamine (6-OHDA)-induced PC12 cell model. The results showed that SCMAC extracts alleviated cell toxicity induced by 6-OHDA and the loss of dopaminergic neurons, which was confirmed by the increase of cell viabilities, inhibition of cell apoptosis, the upregulation of tyrosine hydroxylase (TH) and dopamine transporter (DAT) levels and the downregulation of α-Synuclein level. After purification, 11 compounds were identified by the NMR technique, including a quinone, four phenolic acid derivatives, three ubiquinone derivatives, two alkaloids, and a triterpenoid. The present study suggests that SCMAC could be an attractive candidate for the prevention or treatment of PD. PRACTICAL APPLICATIONS: Parkinson's disease seriously affects the lifetime and quality of the elder population for a long history. Long-term consumption of L-DOPA will result in side effects, such as developing abnormal involuntary movements called dyskinesia. This study showed that natural SCMAC extracts could be a potential therapeutic agent for the treatment of neurodegenerative disorder.

[Differences in maxillary growth vector of skeletal class I with various vertical growth types before and after growth spurts].

OBJECTIVE: To identify the differences in maxillary growth vector with different vertical skeletal patterns of skeletal class I before and after growth spurts. METHODS: One hundred and ninety four cases with different vertical skeletal patterns of skeletal class I were selected and categorized into six groups according to their vertical skeletal patterns and cervical vertebral stages: cervical vertebral maturation stage (CVMS)1,2-horizontal pattern (n=30); CVMS1,2-average pattern (n=32); CVMS1, 2-vertical pattern (n=33); CVMS5, 6-horizontal pattern (n=34); CVMS5, 6-average pattern (n=29); and CVMS5, 6-vertical pattern (n=36). Lateral cephalograms were taken on all of the cases. The angle SN-C axis (theta) and angel PP-C axis (alpha) were measured. RESULTS: (1) The skeletal class I with a vertical growth pattern had larger angle SN-C axis than those with a horizontal or average growth pattern before growth spurts (P(average-vertical) < 0.05, P(horizontal-vertical) < 0.001). (2) The skeletal class I with a vertical growth pattern had the largest angle SN-C axis after growth spurts, followed by those with an average growth pattern. Those with a horizontal growth pattern had the smallest angle SN-C axis. The differences were statistically significant (P(horizontal-average) < 0.05, P(horizontal-vertical) < 0.001, P(average-vertical) < 0.001). (3) The skeletal class I with the same vertical growth pattern had slightly larger angle SN-C axis after growth spurts than before growth spurts, but without statistical significance. (4) The skeletal class I had relatively stable angle PP-C axis and no significant differences were found before and after growth spurts or among those with various vertical skeletal facial types. CONCLUSION: The magnitude of angle SN-C axis is closely associated with vertical growth patterns and is weakly influenced by maxillofacial growth and development.

Efficient Depth Intra Frame Coding in 3D-HEVC by Corner Points.

To improve the coding performance of depth maps, 3D-HEVC includes several new depth intra coding tools at the expense of increased complexity due to a flexible quadtree Coding Unit/Prediction Unit (CU/PU) partitioning structure and a huge number of intra mode candidates. Compared to natural images, depth maps contain large plain regions surrounded by sharp edges at the object boundaries. Our observation finds that the features proposed in the literature either speed up the CU/PU size decision or intra mode decision and they are also difficult to make proper predictions for CUs/PUs with the multi-directional edges in depth maps. In this work, we reveal that the CUs with multi-directional edges are highly correlated with the distribution of corner points (CPs) in the depth map. CP is proposed as a good feature that can guide to split the CUs with multi-directional edges into smaller units until only single directional edge remains. This smaller unit can then be well predicted by the conventional intra mode. Besides, a fast intra mode decision is also proposed for non-CP PUs, which prunes the conventional HEVC intra modes, skips the depth modeling mode decision, and early determines segment-wise depth coding. Furthermore, a two-step adaptive corner point selection technique is designed to make the proposed algorithm adaptive to frame content and quantization parameters, with the capability of providing the flexible tradeoff between the synthesized view quality and complexity. Simulation results show that the proposed algorithm can provide about 66% time reduction of the 3D-HEVC intra encoder without incurring noticeable performance degradation for synthesized views and it also outperforms the previous state-of-the-art algorithms in term of time reduction and ∆ BDBR.

Doxorubicin toxicity changes myocardial energy metabolism in rats.

BACKGROUND: Doxorubicin (DOX) is an antitumor antibiotics used against malignancies. But its toxicity limits the therapy of DOX. OBJECTIVE: The purpose of this study was to evaluate DOX toxicity and the alteration of energy metabolism after short term and long term treatment. METHODS: Male Sprague-Dawley rats were randomly assigned to four groups: Short term control group, short term DOX treatment group, long term control group and long term DOX treatment group. In short term treated group, rats were injected with DOX i.p. at a dose of 2.5 mg/kg every 48 h for six equal injections. In long term, treated group, rats were tail-intravenously injected with DOX at a dose of 3 mg/kg once a week for four weeks. At the end of the experiment, histopathological changes, general blood biomarkers, endogenous antioxidant enzymes, cardiac energy metabolism and related mRNA expression of AMPK signal pathway were determined. RESULTS: DOX induced prominent oxidative stress, a higher mortality rate, histological and ECG changes, obvious cardiac hypertrophy, acute cardiac damage and cardiac energy impairment in short term treatment rats. In long term treatment rats, DOX caused serious nephropathy and systolic dysfunction, terrible cardiac energy impairment, clear alteration of substrate utilization and AMPK signal pathway. CONCLUSION: DOX treatment can induce different damages after short term and long term treatment. In short term treatment group, rats experienced a terrible mortality rate about 40%, the acute cardiac damage, cardiac energy impairment and an early heart failure which are potential connected with reduction of glucose utilization. In the long term treatment group, serious nephropathy and obvious changes of mRNA expressions of AMPK signal pathway were observed. Meanwhile, the serious cardiac energy impairment and substrate utilization alteration denote an obviously heart failure. This study could be helpful to develop therapy strategies of DOX complications for clinical application.