[Role of macrophage polarization in hypertension and traditional Chinese medicine intervention: a review].

Hypertension is known to be a chronic inflammatory state and a key risk factor for heart failure, coronary heart disease, and atherosclerosis. Macrophages in the circulatory system are the main cell group that constitutes the immune system and participates in the inflammatory response. Depending on the local microenvironment, macrophages can be polarized into pro-inflammatory(M1) and anti-inflammatory(M2) phenotypes. When blood pressure is elevated, M1 macrophages can release pro-inflammatory cytokines and chemokines to generate an immune response. However, an excessive immune response can lead to tissue damage, and M2 macrophages release anti-inflammatory cytokines to promote the repair of wounds and tissue damage. It is clear that the dynamic balance between M1 and M2 macrophages resembles the traditional Chinese medicine(TCM) theory of Yin and Yang. That is, when Yin and Yang are imbalanced, the human body will exhibit pathological states, e.g., altered blood pressure rhythms. Studies have confirmed that TCM can produce positive therapeutic effects on hypertension by regulating macrophage polarization. Therefore, this study reviews the studies about the TCM regulation of macrophage polarization and summarized the mechanisms of TCM intervention in hypertension, with the aim of providing evidence for clinical treatment and ideas for scientific research design.

[Network Meta-analysis of Qi-supplementing and Yin-nourishing Chinese patent medicines in treatment of early diabetic nephropathy].

This study aimed to evaluate the efficacy of Qi-supplementing and Yin-nourishing Chinese patent medicine in the treatment of early diabetic nephropathy(DN) by network Meta-analysis to explore the Chinese patent medicine with optimal efficacy and provide references for preventing renal deterioration and delaying the progression of early DN. Eight databases, including CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science, were searched for clinical randomized controlled trial(RCT) of Qi-supplementing and Yin-nourishing Chinese patent medicines in the treatment of early DN. After the literature mee-ting the inclusion criteria was screened, the quality of the literature was evaluated using the Cochrane risk-of-bias tool, and network Meta-analysis was performed using the BUGSnet package in R 4.2.1. Seventy-two research articles with a sample size of 6 344 cases were included, involving eight Chinese patent medicines and seven outcome indicators. The results of the network Meta-analysis showed that(1)in terms of improving urinary albumin excretion rate(UAER), Chinese patent medicines combined with conventional treatment were superior to conventional treatment, and Qiyao Xiaoke Capsules + conventional treatment was optimal.(2)In terms of reducing serum crea-tinine(Scr), Bailing Capsules + conventional treatment had superior efficacy.(3)In terms of reducing 24-hour urine total protein(24hUTP), Shenyan Kangfu Tablets + conventional treatment and Jinshuibao Capsules + conventional treatment had equivalent efficacy, and Shenyan Kangfu Tablets + conventional treatment was superior.(4)In terms of improving fasting blood glucose(FBG), Shenyan Kangfu Tablets + conventional treatment had superior efficacy.(5)In terms of improving total cholesterol(TC), Qiyao Xiaoke Capsules +conventional treatment had superior efficacy.(6)In terms of reducing triglyceride(TG), Bailing Capsules + conventional treatment had superior efficacy.(7)In terms of safety, the occurrence of adverse reactions was reported in seven interventions, but due to the large clinical heterogeneity, the quantitative analysis could not be performed. Overall, Qi-supplementing and Yin-nourishing Chinese patent medicines combined with conventional treatment were superior to conventional treatment alone in the treatment of early DN. The results showed that Qi-supplementing and Yin-nourishing Chinese patent medicines combined with conventional treatment had good clinical efficacy, and they could significantly reduce renal function indicators such as UAER, Scr, and 24hUTP, and reduce blood sugar and blood lipid, which can provide evidence-based support for the treatment of early DN. However, due to the differences in the quantity and quality of the included research articles, large-sample, multi-center, high-quality studies are still needed for further verification.

[Potential targets for traditional Chinese medicine treatment of chronic inflammation in obesity: macrophage polarization].

Obesity has been identified as a chronic low-grade systemic inflammation and a key risk factor for diseases such as diabetes, hypertension, and malignancies, and has become an urgent global health burden. Adipose tissue macrophages play a significant role in adipose immune homeostasis and inflammatory responses. Under different conditions, they can be polarized into pro-inflammatory M1 phenotype or anti-inflammatory M2 phenotype. In obese individuals, there is abnormal polarization of macrophages in adipose tissue, leading to an imbalance in the M1/M2 phenotype dynamic equilibrium and the development of pathological inflammation. Therefore, restoring the balance of M1/M2 macrophage polarization is an important potential target for the treatment of chronic inflammation in obesity. Studies have shown that traditional Chinese medicine(TCM) can positively modulate macrophage polarization and produce beneficial effects on obesity. Based on existing evidence, this paper systematically reviewed the potential mechanisms of TCM in improving chronic inflammation in obesity from the perspective of macrophage polarization, in order to provide evidence for the clinical diagnosis and treatment of chronic inflammation in obesity with TCM and offer new insights for related research design and the development of new TCM.

Silk Protein Composite Bioinks and Their 3D Scaffolds and In Vitro Characterization.

This paper describes the use of silk protein, including fibroin and sericin, from an alkaline solution of Ca(OH)2 for the clean degumming of silk, which is neutralized by sulfuric acid to create calcium salt precipitation. The whole sericin (WS) can not only be recycled, but completely degummed silk fibroin (SF) is also obtained in this process. The inner layers of sericin (ILS) were also prepared from the degummed silk in boiling water by 120 °C water treatment. When the three silk proteins (SPs) were individually grafted with glycidyl methacrylate (GMA), three grafted silk proteins (G-SF, G-WS, G-ILS) were obtained. After adding I2959 (a photoinitiator), the SP bioinks were prepared with phosphate buffer (PBS) and subsequently bioprinted into various SP scaffolds with a 3D network structure. The compressive strength of the SF/ILS (20%) scaffold added to G-ILS was 45% higher than that of the SF scaffold alone. The thermal decomposition temperatures of the SF/WS (10%) and SF/ILS (20%) scaffolds, mainly composed of a ß-sheet structures, were 3 °C and 2 °C higher than that of the SF scaffold alone, respectively. The swelling properties and resistance to protease hydrolysis of the SP scaffolds containing sericin were improved. The bovine insulin release rates reached 61% and 56% after 5 days. The L929 cells adhered, stretched, and proliferated well on the SP composite scaffold. Thus, the SP bioinks obtained could be used to print different types of SP composite scaffolds adapted to a variety of applications, including cells, drugs, tissues, etc. The techniques described here provide potential new applications for the recycling and utilization of sericin, which is a waste product of silk processing.

3,4-Seco-Isopimarane Diterpenes from the Twigs and Leaves of Isodon Flavidus.

Three isopimarane diterpenes [fladins B (1), C (2), and D (3)] were isolated from the twigs and leaves of Chinese folk medicine, Isodon flavidus. The chemical structures were determined by the analysis of the comprehensive spectroscopic data, and the absolute configuration was confirmed by X-ray crystallographic analysis. The structures of 1-3 were formed from isopimaranes through the rearrangement of ring A by the bond break at C-3 and C-4 to form a new δ-lactone ring system between C-3 and C-9. This structure type represents the first discovery of a natural isopimarane diterpene with an unusual lactone moiety at C-9 and C-10. In the crystal of 1, molecules are linked to each other by intermolecular O-H···O bonds, forming chains along the b axis. Compounds 1-3 were evaluated for their bioactivities against different diseases. None of these compounds displayed cytotoxic activities against HCT116 and A549 cancer cell lines, antifungal activities against Trichophyton rubrum and T. mentagrophytes, or antiviral activities against HIV entry at 20 µg/mL (62.9-66.7) µM. Compounds 1 and 3 did not show antiviral activities against Ebola entry at 20 µg/mL either; only 2 was found to show an 81% inhibitory effect against Ebola entry activity at 20 µg/mL (66.7 µM). The bioactivity evidence suggested that this type of compound could be a valuable antiviral lead for further structure modification to improve the antiviral potential.

Henrin A: A New Anti-HIV Ent-Kaurane Diterpene from Pteris henryi.

Henrin A (1), a new ent-kaurane diterpene, was isolated from the leaves of Pteris henryi. The chemical structure was elucidated by analysis of the spectroscopic data including one-dimensional (1D) and two-dimensional (2D) NMR spectra, and was further confirmed by X-ray crystallographic analysis. The compound was evaluated for its biological activities against a panel of cancer cell lines, dental bacterial biofilm formation, and HIV. It displayed anti-HIV potential with an IC50 value of 9.1 µM (SI = 12.2).

Mechanically Robust Poly(vinyl alcohol)-Egg White Composite Hydrogel with Enhancing Biocompatibility by Unidirectional Nanopore Dehydration.

A simple and green method, unidirectional nanopore dehydration (UND), directly processes 10% poly(vinyl alcohol) (PVA) aqueous solution containing 20% egg white (EW) into a composite hydrogel membrane (PVA-EW). The tensile strength and elongation of the UND-based PVA-EW at 25 °C were 0.91 MPa and 534.17%, respectively, while the two values at 70 °C were increased by 700 and 38%, respectively. The PVA-EW (70 °C) was still dominated by random coils and α-helical structures. The hydroxyl groups of intramolecules and intermolecules of both PVA and EW could be able to combine and form either more hydrogen bonds or stronger hydrogen bonds. PVA-EW is soft and translucent, has good mechanical properties, and has a porous networked structure with pores that have a diameter of 1-10 µm. L-929 mouse fibroblasts were found to be able to adhere, grow, and proliferate well on the hydrogel composite membrane. This novel PVA-EW biomaterial has potential applications in biomaterials especially medical tissue engineering.

Silk Fibroin Improves the Biological Properties of Egg White-Based Bioink for the Bioprinting of Tissue Engineering Materials.

Egg white (EW) is a common nutritious food with excellent heat gelation and biocompatibility, but its application in biomaterials is considerably limited. Silk fibroin (SF) is a protein-based fiber with both excellent mechanical properties and biocompatibility, and its application in biomaterials has attracted much attention. Here, the EW/SF composite scaffold was first synthesized with GMA-modified EW/SF composite bioink (G-EW/SF). When homogenized EW and SF were individually grafted with glycidyl methacrylate (GMA), the grafted EW (G-EW) and SF (G-SF) were mixed in different proportions and then added to I2959. The resulting G-EW/SF composite bioink could be bioprinted into various EW/SF composite scaffolds. Among them, the compressive modulus of EW/SF (50%) composite scaffolds incorporating 50% G-SF was significantly improved. It had a three-dimensional (3D) polypore structure with an average pore size of 61 µm and was mainly composed of ß-sheet structures. Compared with the EW scaffold alone, the thermal decomposition temperature of the EW/SF scaffold was 10 °C higher, and the residual rate after 9 days of enzymatic hydrolysis had increased by about 18%. The scaffold prolonged the sustained release of insulin and promoted the adhesion, growth, and proliferation of the L-929 cells. Therefore, the EW/SF composite scaffolds with good cell proliferation ability and certain mechanical properties can be used in different applications including cells, drugs, and tissues. These results provide new prospects for the application of the EW protein to medical tissue engineering materials.

Sesquiterpenoids from the leaves of Sarcandra glabra.

Sarglanoids A-F, six new sesquiterpenoids belonging to eudesmane (1-5) and eremophilane (6) types, were isolated from the leaves of Sarcandra glabra, a famous traditional Chinese medicine (TCM). Their structures including absolute configurations were elucidated through extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. Compounds 1-2 were rare N-containing eudesmane-type sesquiterpenoids. Compound 3 exhibited inhibitory activity against nitric oxide (NO) production in lipopolysaccharides (LPS)-induced RAW 264.7 cells with IC50 values at 20.00 ± 1.30 µmol·L-1. These findings provide scientific evidence for sesquiterpenoids as the material foundation of S. glabra.

Spatio-Temporal Variation in the Phyllospheric Microbial Biodiversity of Alternaria Alternata-Infected Tobacco Foliage.

Phyllospheric microbial composition of tobacco (Nicotiana tabacum L.) is contingent upon certain factors, such as the growth stage of the plant, leaf position, and cultivar and its geographical location, which influence, either directly or indirectly, the growth, overall health, and production of the tobacco plant. To better understand the spatiotemporal variation of the community and the divergence of phyllospheric microflora, procured from healthy and diseased tobacco leaves infected by Alternaria alternata, the current study employed microbe culturing, high-throughput technique, and BIOLOG ECO. Microbe culturing resulted in the isolation of 153 culturable fungal isolates belonging to 33 genera and 99 bacterial isolates belonging to 15 genera. High-throughput sequencing revealed that the phyllosphere of tobacco was dominantly colonized by Ascomycota and Proteobacteria, whereas, the most abundant fungal and bacterial genera were Alternaria and Pseudomonas. The relative abundance of Alternaria increased in the upper and middle healthy groups from the first collection time to the third, whereas, the relative abundance of Pseudomonas, Sphingomonas, and Methylobacterium from the same positions increased during gradual leaf aging. Non-metric multi-dimensional scaling (NMDs) showed clustering of fungal communities in healthy samples, while bacterial communities of all diseased and healthy groups were found scattered. FUNGuild analysis, from the first collection stage to the third one in both groups, indicated an increase in the relative abundance of Pathotroph-Saprotroph, Pathotroph-Saprotroph-Symbiotroph, and Pathotroph-Symbiotroph. Inclusive of all samples, as per the PICRUSt analysis, the predominant pathway was metabolism function accounting for 50.03%. The average values of omnilog units (OUs) showed relatively higher utilization rates of carbon sources by the microbial flora of healthy leaves. According to the analysis of genus abundances, leaf growth and leaf position were the important drivers of change in structuring the microbial communities. The current findings revealed the complex ecological dynamics that occur in the phyllospheric microbial communities over the course of a spatiotemporal varying environment with the development of tobacco brown spots, highlighting the importance of community succession.

[Case control study on anatomical locking plate and ordinary steel plate for the treatment of closed calcaneal fracture with Sandersâ ¡and â ¢].

OBJECTIVE: To compare clinical efficacy between anatomical locking plate (ALP) and ordinary steel plate (OSP) in treating closed calcaneal fractures with SandersⅡ and Ⅲ. METHODS: From May 2016 to May 2018, 68 patients with closed Sanders typeⅡ and Ⅲ calcaneal fractures were retrospectively analyzed, and were divided into anatomical locking plate group (ALP group) and ordinary steel plate group (OSP group) according to two kinds of plate fixation, and 34 patients in each group. In ALP group, there were 21 males and 13 females aged from 20 to 63 years old with average of (35.16±8.45) years old; 14 patients were typeⅡand 20 patients were type Ⅲaccording to Sanders classification;treated with ALP. In OSP group, there were 20 males and 14 females aged from 19 to 63 years old with average of (35.05±8.39) years old;19 patients were typeⅡand 15 patients were type Ⅲ according to Sanders classification;treated with OSP. Operative time, intraoperative blood loss and complications between two groups were observed and compared;preoperative and postoperative Böhler angle and gissane angle were also compared;American Orthopaedic Foot & Ankle Society (AOFAS) ankle and hind foot scores, foot and ankle disability index (FADI) scores were applied to evaluate clinical effect. RESULTS: All patients were followed up from 11 to 14 months with an average of (12.06±0.81) months. There were no statistical differences in opertive time, intraoperative blood loss, incision infection and refracture rate in complications between two groups (P>0.05);while there was significant difference in the number of screw loosening (P<0.05). Böhler angle and Gissane angle in ALP group at 6 and 12 months after opertaion were higher than that of OSP group (P<0.05), and the degree of improvement of Böhler angle and Gissane angle in ALP group were also higher than that of OSP group (P<0.05). Postopertaive AOFAS score and FADI score at 6 and 12 months in ALP group were higher than that of OSP group (P<0.05), while no statistical difference in AOFAS grading between two groups(P>0.05). CONCLUSION: Compared with OSP, ALP in treating SandersⅡ and Ⅲ calcaneal fractures could achieve better therapeutic effect, avoid screw loosening, reduce complications, and improve limb function in further.

Dual energy computed tomography for detection of metastatic lymph nodes in patients with hepatocellular carcinoma.

BACKGROUND: Regional lymph node metastasis in patients with hepatocellular carcinoma (HCC) is not uncommon, and is often under- or misdiagnosed. Regional lymph node metastasis is associated with a negative prognosis in patients with HCC, and surgical resection of lymph node metastasis is considered feasible and efficacious in improving the survival and prognosis. It is critical to characterize lymph node preoperatively. There is currently no consensus regarding the optimal method for the assessment of regional lymph nodes in patients with HCC. AIM: To evaluate the diagnostic value of single source dual energy computed tomography (CT) in regional lymph node assessment for HCC patients. METHODS: Forty-three patients with pathologically confirmed HCC who underwent partial hepatectomy with lymphadenectomy were retrospectively enrolled. All patients underwent dual-energy CT preoperatively. Regional lymph nodes (n = 156) were divided into either a metastatic (group P, n = 52) or a non-metastasis group (group N, n = 104), and further, according to pathology, divided into an active hepatitis (group P1, n = 34; group N1, n = 73) and a non-active hepatitis group (group P2, n = 18; group N2, n = 31). The maximal short axis diameter (MSAD), iodine concentration (IC), normalized IC (NIC), and the slope of the spectral curve (λ HU) of each group in the arterial phase (AP), portal phase (PP), and delayed phase (DP) were analyzed. RESULTS: Analysis of the MSAD, IC, NIC, and λ HU showed statistical differences between groups P and N (P < 0.05) during all three phases. To distinguish benign from metastatic lymph nodes, the diagnostic efficacy of IC, NIC, and λ HU in the PP was the best among the three phases (AP, PP, and DP), with a sensitivity up to 81.9%, 83.9%, and 81.8%, and a specificity up to 82.4%, 84.1% and 84.1%, respectively. The diagnostic value of combined analyses of MSAD with IC, NIC, or λ HU in the PP was superior to the dual energy CT parameters alone, with a sensitivity up to 84.5%, 86.9%, and 86.2%, and a specificity up to 83.0%, 93.6% and 89.8%, respectively. Between groups P1 and P2 and groups N1 and N2, only IC, NIC, and λ HU between groups N1 and N2 in the PP had a statistically significant difference (P < 0.05). CONCLUSION: Dual-energy CT contributes beneficially to regional lymph node assessment in HCC patients. Combination of MSAD with IC, NIC, or λ HU values in the PP is superior to using any single parameter alone. Active hepatitis does not deteriorate the capabilities for characterization of metastatic lymph nodes.

New bisabolane sesquiterpenes and coumarin from Leontopodium longifolium.

From the roots of Leontopotium longifolium, three new bisabolane sesquiterpenes, rel-(1S,4R,5S,6R)-4,5-diacetoxy-6-[(R)-1,5-dimethylhexa-3,5-dienyl]-3-methylcyclohex-2-enyl (Z)-2-methylbut-2-enoate (1), rel-(1S,4R,5S,6R)-4,5-diacetoxy-6-[(R)-5-hydroxy-1,5-dimethylhex-3-enyl]-3-methylcyclohex-2-enyl (Z)-2-methylbut-2-enoate (2), rel-(1R,2S,4R,5S)-4-acetoxy-2-[(R)-5-hydroxy-1,5-dimethylhex-3-enyl]-5-methylcyclohexyl (Z)-2-methylbut-2-enoate (3), and a new coumarin, 2,3-dihydro-5-hydroxy-2-(1-methylethenyl)-7H-pyrano[2,3-g][1,4]benzodioxin-7-one (4) together with nine known compounds have been isolated. The structures of these compounds were established by spectroscopic methods. Compounds 1 and 2 exhibited moderate cytotoxic activities against human promyelocytic leukemia (HL-60) cells.

Discovery of antifungal constituents from the Miao medicinal plant Isodon flavidus.

ETHNOPHARMACOLOGICAL RELEVANCE: Leigong Mountain is an area in the Southwest of China where there is a high incidence rate of athlete's foot, but the Miao people, a Chinese minority who reside in this mountainous area have suffered less from this disease due to their use of the herbal medicine Isodon flavidus (Hand.-Mazz.) H. Hara. AIM OF THE STUDY: The present study is to identify the active chemical constituents responsible for antifungal effects of the folk medicine plant. MATERIALS AND METHODS: The natural compounds were separated from the methanol extract of the twigs and leaves of I. flavidus by phytochemical study using chromatographic methods, and their chemical structures were determined by analysis of the spectroscopic data including 1D and 2D NMR spectra. The absolute configuration of fladin A (1) was further confirmed by X-ray crystallographic analysis. The compounds were evaluated for their antifungal activity against the athlete's foot fungus Trichophyton rubrum. They were further evaluated for their antimicrobial and anti-biofilm activity against the dental pathogens Streptococcus mutans, Porphyromonas gingivalis and Candida albicans. RESULTS: Phytochemical and biological studies of I. flavidus led to the discovery of two antifungal compounds, fladin A (1) and lophanic acid (2). Fladin A (1) is a novel diterpene with an unprecedented cyclic ether group formed between C-4 and C-9. Lophanic acid (2) displayed inhibition activity against the athlete's foot fungus Trichophyton rubrum with an MIC value of 7.8µg/mL, and fladin A (1) also showed inhibition activity against the fungus with a MIC value of 62.5µg/mL. CONCLUSIONS: Our identification of two antifungal compounds provided strong evidence for the Miao people to use I. flavidus as a medicinal plant for treatment of athlete's foot disease. The very different chemical structures of the active compounds from those in the market presents them as potential antifungal lead compounds for follow-up study.

Sesquiterpenes and other constituents from Achillea wilsoniana.

From the methanol extract of the whole plant of Achillea wilsoniana, 23 compounds were isolated. Their structures were elucidated by spectroscopic methods and chemical transformations. Three of them are new: 4E, 10E-9beta-hydroxy-3-(2-methylbutyroyloxy)-germacra-4,10(1)-diene-12,6alpha-olide (1), 4E,10E-3-(2-methylbutyroyloxy)-germacra-4,10(1)-diene-12,6alpha-olide (2) and 1beta,6a-dihydroxy-10beta-methyl-5alphaH,7alphaH-eudesm-4-one (3). In addition, 1beta-hydroxy-alpha-xyperone (5) and 9beta-acetoxy-3-(2methylbutyroyloxy)-germacra-4,10(1)-diene-12,6alpha-olide (1a) exhibited effective antibacterial activity against Staphylococcus aureus.

[Correlation between endogenous harmful components in mainstream cigarette smoke and chemical constituents in tobacco leaves].

Correlation analysis between main chemical constituents of tobacco leaves and endogenous harmful components in mainstream cigarette smoke was conducted. Leaf stalk positions exhibited a high relation with endogenous harmful components and hazard index (H). Upper stalk position leaves had greater release of 1-butanone,4-(methylnitrosoamino)-1-(3-pyridinyl)-(NNK), B[a]P, HCN, NH3 and phenol in mainstream cigarette smoke, and a higher hazard index than middle position leaves except for crotonaldehyde, which had greater release from middle position leaves. Different endogenous harmful components in mainstream cigarette smoke presented complicated correlation with main chemical constituents in tobacco. The same type of leaf chemical constituents presented different correlations with various endogenous harmful components in mainstream cigarette smoke. Cigarette hazard index showed significantly positive correlations with contents of nicotine, protein, total nitrogen, major polyphenols and organic acids, while significantly negative correlation with potassium and carbonaceous substances, such as total sugars, reducing sugars and starch. The results suggested that properly increasing potassium content and decreasing nitrogenous constituents in cured tobacco leaf may reduce the cigarette hazard index.