Role of miRNAs in macrophage-mediated kidney injury.

Macrophages, crucial components of the human immune system, can be polarized into M1/M2 phenotypes, each with distinct functions and roles. Macrophage polarization has been reported to be significantly involved in the inflammation and fibrosis observed in kidney injury. MicroRNA (miRNA), a type of short RNA lacking protein-coding function, can inhibit specific mRNA by partially binding to its target mRNA. The intricate association between miRNAs and macrophages has been attracting increasing interest in recent years. This review discusses the role of miRNAs in regulating macrophage-mediated kidney injury. It shows how miRNAs can influence macrophage polarization, thereby altering the biological function of macrophages in the kidney. Furthermore, this review highlights the significance of miRNAs derived from exosomes and extracellular vesicles as a crucial mediator in the crosstalk between macrophages and kidney cells. The potential of miRNAs as treatment applications and biomarkers for macrophage-mediated kidney injury is also discussed.

Impact of proton pump inhibitor management committee's multifaceted interventions on acid suppressant prescribing patterns in outpatient and emergency departments.

BACKGROUND: A nationwide campaign for rational proton pump inhibitor (PPI) use launched in 2015 had a positive impact for hospitalized patients PPI use. But there were few studies focusing on the rational use of PPIs in outpatients. In 2018, the PPI management committee conducted a year-long intervention on the appropriate use of PPIs in outpatient and emergency departments, including clinical pharmacist interventions and stewardship interventions. The purpose of this study was to examine the impact of the PPI management committee's multifaceted interventions by comparing the real-world acid suppressant prescribing patterns for outpatients before (2017) and after intervention (2019) at a Chinese tertiary teaching hospital. METHODS: Prescriptions containing any acid suppressant in outpatient and emergency departments in baseline (2017) and postintervention (2019) periods were extracted from the hospital information system and the prescription automatic screening system. Acid suppressant prescribing patterns were evaluated based on primary diagnoses and patient demographics. The prescribed acid suppressants stratified using age groups (< 7, 7-17, 18-45, 46-65, 66-85 and > 85 years) were also examined. RESULT: The utilization rate of acid suppressant in 2017 and 2019 was 2.5% (41,165/1,619,366) and 2.2% (49,550/2,236,471), respectively (P < 0.0001). 60,135 acid suppressant prescriptions were obtained in 2017 and 73,275 in 2019. The rate of acid suppressant prescriptions for the approved indications significantly increased from 62.6% (2017) to 65.4% (2019) (P < 0.0001). Prescriptions diagnosed as abnormal symptoms, signs and clinical manifestations, decreased in 2019 (13.0% vs. 16.5%, P < 0.0001). The most frequently prescribed PPIs differed between 2017 and 2019 (rabeprazole 2017 vs. esomeprazole 2019). Omeprazole was the most common PPI and cimetidine was the most common H2RA prescribed to patients aged < 18 years in 2017 and 2019. A total of CNY11.83 million was spent on acid suppressants in 2019, accounting for about 48.7% of total medication cost, increased by 11.3% from 2017 (37.4%). CONCLUSION: The proportion of acid suppressant prescriptions for approved indications was enhanced after the PPI management committee's multifaceted interventions, but there were still some problems in the selection of acid suppressants.

Changes of BKCA current and vascular reactivity in vascular smooth muscle of thoracic aorta and mesenteric artery in type 2 diabetic rats.

The relationship between large conductance calcium activated potassium channel (BKCa) and vascular lesions in type 2 diabetes mellitus (T2DM) was investigated by observing vascular reactivity of thoracic aorta and mesenteric artery and the current changes of BKCa in vascular smooth muscle cells (VSMCs). The thoracic aorta and mesenteric artery of T2DM rats were isolated, the whole cell perforated patch clamp experiment and single channel patch clamp experiment of acute enzyme separation of thoracic aorta and mesenteric artery smooth muscle cells were performed to measure the membrane capacitance and the amplitude of macro current. And the vascular ring experiment was performed to observe the change of relaxation percentage. The results showed that the amplitude of BKCa current in vascular smooth muscle cells of diabetic rats was higher than that of the control group. The channel current had outward rectifying characteristics. BKCa is related to vascular reactivity and smooth muscle relaxation in T2DM rats. The opening probability of BKCa in VSMCs of diabetic rats was significantly increased. This study suggests that BKCa may be a new target for diabetic vascular disease.

The distinct roles of exosomes in tumor-stroma crosstalk within gastric tumor microenvironment.

Gastric cancer (GC) development is a complex process displaying polytropic cell and molecular landscape within gastric tumor microenvironment (TME). Stromal cells in TME, including fibroblasts, endothelial cells, mesenchymal stem cells, and various immune cells, support tumor growth, metastasis, and recurrence, functioning as the soil for gastric tumorigenesis. Importantly, exosomes secreted by either stromal cells or tumor cells during tumor-stroma crosstalk perform as crucial transporter of agents including RNAs and proteins for cell-cell communication in GC pathogenesis. Therefore, given the distinct roles of exosomes secreted by various cell types in GC TME, increasing evidence has indicated that exosomes present as new biomarkers for GC diagnosis and prognosis and shed light on novel approaches for GC treatment.

[Pueraria lobate advances in molecular pharmacognosy].

Molecular pharmacognosy is a science of classification and identification, cultivation and protection, and production of active ingredients of graduated drugs at the molecular level. The proposal of molecular pharmacognosy allows the research of crude drugs to advance from the microscopic level to the genetic level. Pueraria lobata root, as a medicinal and edible plant, has high application value and economic value. There are many varieties that are easy to cause confusion, and it is not easy to distinguish and identify according to traditional identification methods. Moreover, the research of P. lobate root at the genetic level is still relatively shallow. the study received extensive attention of scholars. This article reviews recent research on molecular identification of P. lobate, transcriptome sequencing, cloning and synthesis of functional genes of P. lobate root in recent years in order to provide references for further promoting the development and utilization of P. lobate root and its active ingredients.

[Correlation between color and content of eight components of Gardeniae Fructus at different harvest time].

This research is to establish an HPLC method for determination of geniposidic acid, genipin-1-ß-D-gentiobioside, geniposide, p-trans-coumaroylgenipin gentiobioside, chlorogenic acid, crocin-Ⅰ, crocin-Ⅱ and crocin-Ⅲ in Gardeniae Fructus at different harvest time. The detection wavelength was 238, 320 and 440 nm. Principal component analysis(PCA), correlation analysis, regression analysis and partial least squares(PLS) analysis were used to explore the relationship of color and content of eight components in Gardeniae Fructus. The result showed that the trend of the eight components in Gardeniae Fructus at harvest time in different three years was varied similarly. According to the variation of eight components at different harvest time, the mature and immaturate Gardeniae Fructus were discriminated. The content of crocin-Ⅰwas correlated positively with a~* of color significance. The redder color of Gardeniae Fructus showed the higher value of a~* and content of crocin-Ⅰ, indicating the better quality of Gardeniae Fructus. This method provided reference for justifying the color and quality of Gardeniae Fructus and scientific evidence for "assessing quality by distinguishing color".

Changes in chronic disease management among community health centers (CHCs) in China: Has health reform improved CHC ability?

Since the 1980s, China has been criticized for its mode of chronic disease management (CDM) that passively provides treatment in secondary and tertiary hospitals but lacks active prevention in community health centers (CHCs). Since there are few systematic evaluations of the CHCs' methods for CDM, this study aimed to analyze their abilities. On the macroperspective, we searched the literature in China's largest and most authoritative databases and the official websites of health departments. Literature was used to analyze the government's efforts in improving CHCs' abilities to perform CDM. At the microlevel, we examined the CHCs' longitudinal data after the New Health Reform in 2009, including financial investment, facilities, professional capacities, and the conducted CDM activities. A policy analysis showed that there was an increasing tendency towards government efforts in developing CDM, and the peak appeared in 2009. By evaluating the reform at CHCs, we found that there was an obvious increase in fiscal and public health subsidies, large-scale equipment, general practitioners, and public health physicians. The benefited vulnerable population in this area also rose significantly. However, rural centers were inferior in their CDM abilities compared with urban ones, and the referral system is still not effective in China. This study showed that CHCs are increasingly valued in managing chronic diseases, especially after the New Health Reform in 2009. However, we still need to improve collaborative management for chronic diseases in the community and strengthen the abilities of CHCs, especially in rural areas.

[Varieties textual research, resource investigation and identification of commercial drugs on Cuscutae Semen].

Through the textual research, resource investigation, literature reviews (including Flora of China, municipal Flora, pharmacopoeia of China and municipal drug standards) and identification of commercial drugs on Cuscutae Semen, it was found the species described in the herbal textual was Cuscuta chinensis, with good quality from Shandong and Henan Province. The identification of commodities showed the majority drugs were from C. australis, varied from the ancient herbal textuals .Mordern literature reviews indicate that it was necessary to strengthen the research on Cuscutae Semen from C. australis, C. chinensis and C. japonica because of their differences in resources, macroscopical and microscopical characters, while wrong descriptions in some literatures. It was suggested that the two species (C. australis and C. chinensis) should be separated in pharmacopoeia of China. The study provides scientific basis for the development and utilization of Cuscutae Semen.

[Chemical Constituents from Xanthium mongolicum].

Objective: To investigate the chemical constituents from Xanthium mongolicum. Methods: The constituents were isolated and purified by silicagel,Sephadex LH-20 column chromatography. Their structures were identified on the basis of spectral data and physiochemical characteristics. Results: Ten compounds were isolated and identified as hexadecanoic acid( 1), methyl 3, 4-dihydroxybenzoate ( 2), protocatechuic aldehyde( 3), caffeic acid methyl ester( 4), vanillic acid( 5), 4-hydroxybenzoic acid( 6), caffeic acid ethyl ester( 7), chlorogenic acid( 8), caffeic acid( 9), 3, 4-di-O-caffeoylquinic acid( 10). Conclusion: Compounds 1 ~ 5,7 and 10 are isolated from this plant for the first time.

[Pharmacognostical study on four origin plants of folk medicine Sikuaiwa].

In order to develop characteristic folk medicine resources in Jiangxi, a pharmacognostical study was systematically performed for four different origin plants of Sikuaiwa, the result of study provides the microscopic features of powder and tissue of the crude drug. The research provided reference for the identification of Sikuaiwa, as well as a theoretical basis for the further development and the formulation of quality standards.

[Histomorphological study on folk medicine Lysimachia fortunei].

To set standards for histomorphological studies on Lysimachia fortunei, an efficacious and widely applied folk medicine in this study, in order to develop its resources. Its species were identified by observing plant morphology and herbs appearance characters, preparing slices with routine methods and defining structural characters. According to the results of morphologic observation, leaves, stamen and pistil of this plant were different from the descriptions in Flora of China. The whole herb can be used in medicines, mainly including rhizomes, stems and leaves. According to the findings in the first study on microscopic structures, its rhizomes, stems and leaves were characteristic and worth identifying. The transaction tissue structures of rhizomes and stems were under developed and contained endodermis, secretory structures; Stems had sclerenchymata of different shapes of sclereids; Leaves were bifacial and had vascular bundles under midribs, which were surrounded by parenchymal sheathes. On the surface of leaves, stomata, glandular hairs and keratin lines were morphologically different in upper and lower epidermis. The herbal power had glandular hairs, sclereids and vessels. In conclusion, herbs of L. fortunei can be identified by the above histomorphological characteristics, which lays a foundation for further development and application of L. fortunei.

DDX5 inhibits hyaline cartilage fibrosis and degradation in osteoarthritis via alternative splicing and G-quadruplex unwinding.

Hyaline cartilage fibrosis is typically considered an end-stage pathology of osteoarthritis (OA), which results in changes to the extracellular matrix. However, the mechanism behind this is largely unclear. Here, we found that the RNA helicase DDX5 was dramatically downregulated during the progression of OA. DDX5 deficiency increased fibrosis phenotype by upregulating COL1 expression and downregulating COL2 expression. In addition, loss of DDX5 aggravated cartilage degradation by inducing the production of cartilage-degrading enzymes. Chondrocyte-specific deletion of Ddx5 led to more severe cartilage lesions in the mouse OA model. Mechanistically, weakened DDX5 resulted in abundance of the Fn1-AS-WT and Plod2-AS-WT transcripts, which promoted expression of fibrosis-related genes (Col1, Acta2) and extracellular matrix degradation genes (Mmp13, Nos2 and so on), respectively. Additionally, loss of DDX5 prevented the unfolding Col2 promoter G-quadruplex, thereby reducing COL2 production. Together, our data suggest that strategies aimed at the upregulation of DDX5 hold significant potential for the treatment of cartilage fibrosis and degradation in OA.

[Comparative research on histological and microscopical leaves characters of five species in Chloranthus].

OBJECTIVE: To clarify the origin and provide pharmacognostical evidences for the leaves of 5 species in Chloranthus. METHOD: Histological observation and microscopic identification through different slice-making techniques were applied to the research. RESULT: There were subtle differences between the histological characteristics. In microscopical identification, the different structures of vascular bundles in veins were observed, appendages and non-glandular hairs were distinct. CONCLUSION: The method can be used to distinguish the features of 5 species in Chloranthus. This article offers information for the further research and exploitation of Chloranthus.

Pharmacological properties and underlying mechanisms of aurantio­obtusin (Review).

Herbal medicine has been widely applied for a range of diseases in China since antiquity. Cassia obtusifolia L. and Cassia tora L. are plants whose seeds have high reported medicinal values and have been documented to function as a laxative, to lower lipid level and to lower blood pressure. The main active ingredient in Cassia seeds is aurantio-obtusin (AO), which is an anthraquinone monomer compound. Currently, AO is listed in China as a quality control index component of Cassia seeds. In clinical practice in China, AO is typically used to treat obesity, diabetes and its complications, non-alcoholic fatty liver disease and allergic reactions. In addition, AO has been reported to confer insecticidal activities and antimalarial effects. Previous studies have even suggested that AO is a potential therapeutic candidate for a variety of diseases with research value. Therefore, the present review summarizes and discuss the existing literature on AO to provide a review of its pharmacological activity and mechanism of action, with the aim of providing a basis for its development and utilization in a clinical setting.

Secular trend analysis of antibiotic utilisation in some hospitals in Southern Sichuan from 2010 to 2020.

In order to assess the effectiveness of the Special Antimicrobial Stewardship Campaign launched by Ministry of Health of China in 2011, this study focused on the effectiveness and trends in the clinical use of antimicrobial drugs in selected hospitals in Southern Sichuan, China. This study collected and analyzed antibiotic data from 9 hospitals in Southern Sichuanin 2010, 2015, and 2020, including the rate of antibiotic use, expense, the intensity of antibiotic use and antibiotic use during the type I incisions of perioperative period. After 10 years of continuous improvement, the utilization rate of antibiotics in outpatients of the 9 hospitals continued to decline and was controlled below 20% by 2020, while the utilization rate in inpatients also significantly decreased, most were controlled within 60%. The use intensity of antibiotics (DDD (defined daily doses) per 100 bed-days) decreased from an average of 79.95 in 2010 to 37.96 in 2020. The prophylactic use of antibiotics decreased significantly in type I incision. The proportion of use within 30 min-1 h before operation was significantly increased. After the special rectification and sustained development of the clinical application of antibiotics, the relevant indicators of antibiotics tend to be stable, indicating that this Administration of antimicrobial drugs is conducive to improving the level of rational clinical application of antibiotics.

Role of miR­181a­5p in cancer (Review).

MicroRNAs (miRNAs) are non­coding RNAs (ncRNAs) that can post­transcriptionally suppress targeted genes. Dysregulated miRNAs are associated with a variety of diseases. MiR­181a­5p is a conserved miRNA with the ability to regulate pathological processes, such as angiogenesis, inflammatory response and obesity. Numerous studies have demonstrated that miR­181a­5p exerts regulatory influence on cancer development and progression, acting as an oncomiR or tumor inhibitor in various cancer types by impacting multiple hallmarks of tumor. Generally, miR­181a­5p binds to target RNA sequences with partial complementarity, resulting in suppression of the targeted genes of miR­181a­5p. However, the precise role of miR­181a­5p in cancer remains incompletely understood. The present review aims to provide a comprehensive summary of recent research on miR­181a­5p, focusing on its involvement in different types of cancer and its potential as a diagnostic and prognostic biomarker, as well as its function in chemoresistance.

ChIP-Hub provides an integrative platform for exploring plant regulome.

Plant genomes encode a complex and evolutionary diverse regulatory grammar that forms the basis for most life on earth. A wealth of regulome and epigenome data have been generated in various plant species, but no common, standardized resource is available so far for biologists. Here, we present ChIP-Hub, an integrative web-based platform in the ENCODE standards that bundles >10,000 publicly available datasets reanalyzed from >40 plant species, allowing visualization and meta-analysis. We manually curate the datasets through assessing ~540 original publications and comprehensively evaluate their data quality. As a proof of concept, we extensively survey the co-association of different regulators and construct a hierarchical regulatory network under a broad developmental context. Furthermore, we show how our annotation allows to investigate the dynamic activity of tissue-specific regulatory elements (promoters and enhancers) and their underlying sequence grammar. Finally, we analyze the function and conservation of tissue-specific promoters, enhancers and chromatin states using comparative genomics approaches. Taken together, the ChIP-Hub platform and the analysis results provide rich resources for deep exploration of plant ENCODE. ChIP-Hub is available at https://biobigdata.nju.edu.cn/ChIPHub/ .

Salvianolic acid B inhibits RAW264.7 cell polarization towards the M1 phenotype by inhibiting NF-κB and Akt/mTOR pathway activation.

M1 macrophages secrete a large number of proinflammatory factors and promote the expansion of atherosclerotic plaques and processes. Salvianolic acid B (Sal B) exerts anti-inflammatory, antitumor and other effects, but no study has addressed whether Sal B can regulate the polarization of macrophages to exert these anti-atherosclerotic effects. Therefore, we investigated the inhibition of Sal B in M1 macrophage polarization and the underlying mechanism. The effects of different treatments on cell viability, gene expression and secretion of related proteins, phenotypic markers and cytokines were detected by MTT and western blot assays, RT‒qPCR and ELISAs. Cell viability was not significantly changed when the concentration of Sal B was less than 200 µM, and Lipopolysaccharide (LPS) (100 ng/mL) + interferon-γ (IFN-γ) (2.5 ng/mL) successfully induced M1 polarization. RT‒qPCR and ELISAs indicated that Sal B can downregulate M1 marker (Inducible Nitric Oxide Synthase (iNOS), Tumor Necrosis Factor-α (TNF-α), and Interleukin-6 (IL-6)) and upregulate M2 marker (Arginase-1 (Arg-1) and Interleukin-10 (IL-10)) expression. Western blotting was performed to measure the expression of Nuclear Factor-κB (NF-κB), p-Akt, p-mTOR, LC3-II, Beclin-1, and p62, and the results suggested that Sal B inhibits the M1 polarization of RAW264.7 macrophages by promoting autophagy via the NF-κB signalling pathway. The study indicated that Sal B inhibits M1 macrophage polarization by inhibiting NF-κB signalling pathway activation and downregulating Akt/mTOR activation to promote autophagy.

Allosteric inhibition reveals SHP2-mediated tumor immunosuppression in colon cancer by single-cell transcriptomics.

Colorectal cancer (CRC), a malignant tumor worldwide consists of microsatellite instability (MSI) and stable (MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing was performed to explore the role of SHP2 in all cell types of tumor microenvironment (TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68+ macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively, our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy.

Alpha-solanine Anti-tumor Effects in Non-small Cell Lung Cancer Through Regulating the Energy Metabolism Pathway.

BACKGROUND: Lung cancer is a malignant tumor with a high incidence in China, especially non-small cell lung cancer (NSCLC), which is the main threat to human life, with terrible morbidity and mortality. The research on the treatment and mechanism of NSCLC has been the forefront and hotspot of research. Recent patents show that alpha-solanine (α-solanine) exhibits the best anti-cancer activity, although its target and related mechanism remain to be elucidated. OBJECTIVES: This study aims to explore the possible targets and mechanisms of α-solanine in the treatment of NSCLC through network pharmacology and experimental verification. METHODS: Network pharmacology was applied to screen the possible targets of α-solanine on NSCLC, construct core networks, and perform GO enrichment and KEGG pathway analysis to predict the mechanism of α-solanine against NSCLC. Experiments were implemented to verify the results of network pharmacology in vitro. The A549 and PC-9 cells were exposed to α-solanine to assess the anti-tumor effect. Cell apoptosis was determined by the Annexin-V/PI assay. Targeted energy metabolomics was used to validate the network pharmacology results, and energy metabolism pathway- related proteins were detected by immunofluorescence and western blot. RESULTS: Network pharmacology showed that there were 130 potential targets of α-solanine and NSCLC. GO, and KEGG analysis showed that the energy metabolism pathway is the main pathway for α-solanine to exert anti-tumor effects on NSCLC. Experimental results showed that α-solanine inhibited cell proliferation, migration, invasion and promoted cell apoptosis. At the same time, after α-solanine treatment, the energy metabolism pathway-related proteins, including GPI, ALDOA, TPI1, PKLR, LDHA, and ALDH3, were expressed reduced. In addition, α-solanine also affects the amino acid metabolism of A549 and PC-9 cells. CONCLUSION: Based on a combination of network pharmacological prediction and experimental verification, α-solanine may exert anti-NSCLC effects by regulating the energy metabolism pathway.