Challenges in the study of self-assembled aggregates in decoction of traditional Chinese medicine: A preliminary review / 药学学报

Decoction is the most commonly used dosage form in the clinical treatment of traditional Chinese medicine (TCM). During boiling, the violent movement of various active ingredients in TCM creates molecular forces such as hydrogen bonding, π-π stacking, hydrophobic interactions and electrostatic interactions, which results in the formation of self-assembled aggregates in decoction (SADs), including particles, gels, fibers, etc. It was found that SADs widely existed in decoction with biological activities superior to both effective monomers and their physical mixtures, providing a new idea to reveal the pharmacodynamic material basis of Chinese herbal medicine from the perspective of component interactions-phase structure. Recently, SADs have become a novel focus of research in TCM. This paper reviewed their relevant studies in recent years and found some issues to be concerned in the research, such as the polydispersity of decoction system, instability of active ingredient interactions during boiling, uncertainty of the aggregates self-assembly rules, and stability, purity, yield of the products. In this regard, some solutions and new ideas were presented for the integrated development and clinical application of SADs.

Effect of remnant cholesterol levels on carotid intima thickness in patients with type 2 diabetes mellitus evaluated by ultra-high frequency ultrasound / 中华超声影像学杂志

Objective:To discuss the effect of remnant cholesterol (RC) levels on carotid intima thickness (CIT) in patients with type 2 diabetes mellitus (T2DM) by ultra-high frequency ultrasound.Methods:A total of 60 patients with T2DM who received treatment in Henan Provincial People′s Hospital from May 2021 to July 2022 were prospectively recruited, and they were divided into a higher RC group (31 cases) and a lower RC group (29 cases) according to the RC levels. Thirty-one age, sex and body mass index(BMI)-matched healthy volunteers were selected as control group. Carotid CIT, carotid media thickness(CMT) and intima-media thickness(CIMT) were measured by 24 MHz ultra-high frequency ultrasound probe. The difference of general clinical data, laboratory indicators and CIMT, CIT, CMT among the three groups were compared, and the influencing factors of CIT in T2DM patients were explored by multivariate regression analysis.Results:①There were no statistical significances in gender, age, BMI, high-density lipoprotein cholesterol (HDL-C) and CMT among the three groups (all P>0.05). There were no statistical significances in duration of diabetes, fasting blood-glucose and glycated haemoglobin between the two subgroups of T2DM (all P>0.05). ②Compared with the control group, CIMT and CIT were thicker in the T2DM group (both P<0.05). ③CIT was thicker in the higher RC group than in the lower RC group ( P<0.05), while the difference of CIMT was not statistically significant the two groups ( P>0.05). ④Multivariate regression analysis showed that RC was the influence factor of CIT in patients with T2DM(β=0.610, P=0.005). Conclusions:CIT is significantly thicker in T2DM patients with higher RC than in those with lower RC, and RC is the influence factor of CIT, which suggests that more attention should be paid to the detection of RC in T2DM patients.

PKM2-mediated neuronal hyperglycolysis enhances the risk of Parkinson's disease in diabetic rats / 药物分析学报

Epidemiological and animal studies indicate that pre-existing diabetes increases the risk of Parkinson's disease(PD).However,the mechanisms underlying this association remain unclear.In the present study,we found that high glucose(HG)levels in the cerebrospinal fluid(CSF)of diabetic rats might enhance the effect of a subthreshold dose of the neurotoxin 6-hydroxydopamine(6-OHDA)on the development of motor disorders,and the damage to the nigrostriatal dopaminergic neuronal pathway.In vitro,HG promoted the 6-OHDA-induced apoptosis in PC12 cells differentiated to neurons with nerve growth factor(NGF)(NGF-PC12).Metabolomics showed that HG promoted hyperglycolysis in neurons and impaired tricarboxylic acid cycle(TCA cycle)activity,which was closely related to abnormal mito-chondrial fusion,thus resulting in mitochondrial loss.Interestingly,HG-induced upregulation of pyruvate kinase M2(PKM2)combined with 6-OHDA exposure not only mediated glycolysis but also promoted abnormal mitochondrial fusion by upregulating the expression of MFN2 in NGF-PC12 cells.In addition,we found that PKM2 knockdown rescued the abnormal mitochondrial fusion and cell apoptosis induced by HG+6-OHDA.Furthermore,we found that shikonin(SK),an inhibitor of PKM2,restored the mito-chondrial number,promoted TCA cycle activity,reversed hyperglycolysis,enhanced the tolerance of cultured neurons to 6-OHDA,and reduced the risk of PD in diabetic rats.Overall,our results indicate that diabetes promotes hyperglycolysis and abnormal mitochondrial fusion in neurons through the upre-gulation of PKM2,leading to an increase in the vulnerability of dopaminergic neurons to 6-OHDA.Thus,the inhibition of PKM2 and restoration of mitochondrial metabolic homeostasis/pathways may prevent the occurrence and development of diabetic PD.

Pathological features of early gastric cancer and its background mucosa after eradication of Helicobacter pylori and their implications for biopsy diagnosis / 中华病理学杂志

Objective: To investigate the clinicopathological changes of early gastric cancer, especially its background mucosa, after the eradication of Helicobacter pylori (H. pylori), and to investigate the causes of underdiagnosis in preoperative biopsy pathology. Methods: Ninety cases of early gastric cancer after H. pylori eradication and 120 cases of endoscopic submucosal dissection (ESD) specimens without H. pylori eradication and their corresponding biopsy specimens were collected from Beijing Friendship Hospital Affiliated to Capital Medical University during 2016-2021. The clinicopathological data of the patients were analyzed, and the histopathological characteristics and immunophenotypic results compared. Results: Compared with the early gastric cancer without H. pylori eradication history, the histopathological type of early gastric cancer after H. pylori eradication was differentiated adenocarcinoma, with staggered distribution of cancerous and non-cancerous epithelium in the tumor area. The morphologic characteristics of gastric mucosa in the background of early gastric cancer after H. pylori eradication, were distinctive, including widening of the opening of enterosylated glandular ducts, serrated change of luminal margin, eosinophilic and microvesicular cytoplasm of enterosylated epithelium. Low-grade atypia existed in gastric cancer epithelial cells after sterilization, which might lead to underdiagnosis or missed diagnosis in biopsy pathology. Conclusions: Early gastric cancer and its background mucosa after H. pylori eradication have unique morphological characteristics, which can be used as a clue for pathological diagnosis, improve the accuracy of biopsy pathology and reduce the underdiagnosis.

Complete chloroplast genome sequencing and phylogeny of wild Atractylodes lancea from Yuexi, Anhui province / 中国中药杂志

This study investigated the choroplast genome sequence of wild Atractylodes lancea from Yuexi in Anhui province by high-throughput sequencing, followed by characterization of the genome structure, which laid a foundation for the species identification, analysis of genetic diversity, and resource conservation of A. lancea. To be specific, the total genomic DNA was extracted from the leaves of A. lancea with the improved CTAB method. The chloroplast genome of A. lancea was sequenced by the high-throughput sequencing technology, followed by assembling by metaSPAdes and annotation by CPGAVAS2. Bioiformatics methods were employed for the analysis of simple sequence repeats(SSRs), inverted repeat(IR) border, codon bias, and phylogeny. The results showed that the whole chloroplast genome of A. lancea was 153 178 bp, with an 84 226 bp large single copy(LSC) and a 18 658 bp small single copy(SSC) separated by a pair of IRs(25 147 bp). The genome had the GC content of 37.7% and 124 genes: 87 protein-coding genes, 8 rRNA genes, and 29 tRNA genes. It had 26 287 codons and encoded 20 amino acids. Phylogenetic analysis showed that Atractylodes species clustered into one clade and that A. lancea had close genetic relationship with A. koreana. This study established a method for sequencing the chloroplast genome of A. lancea and enriched the genetic resources of Compositae. The findings are expected to lay a foundation for species identification, analysis of genetic diversity, and resource conservation of A. lancea.

Activation of insulin-like growth factor-1 receptor (IGF-1R) promotes growth of colorectal cancer through triggering the MEX3A-mediated degradation of RIG-I

Insulin-like growth factor-1 receptor (IGF-1R) has been made an attractive anticancer target due to its overexpression in cancers. However, targeting it has often produced the disappointing results as the role played by cross talk with numerous downstream signalings. Here, we report a disobliging IGF-1R signaling which promotes growth of cancer through triggering the E3 ubiquitin ligase MEX3A-mediated degradation of RIG-I. The active β-arrestin-2 scaffolds this disobliging signaling to talk with MEX3A. In response to ligands, IGF-1Rβ activated the basal βarr2 into its active state by phosphorylating the interdomain domain on Tyr64 and Tyr250, opening the middle loop (Leu130‒Cys141) to the RING domain of MEX3A through the conformational changes of βarr2. The models of βarr2/IGF-1Rβ and βarr2/MEX3A could interpret the mechanism of the activated-IGF-1R in triggering degradation of RIG-I. The assay of the mutants βarr2Y64A and βarr2Y250A further confirmed the role of these two Tyr residues of the interlobe in mediating the talk between IGF-1Rβ and the RING domain of MEX3A. The truncated-βarr2 and the peptide ATQAIRIF, which mimicked the RING domain of MEX3A could prevent the formation of βarr2/IGF-1Rβ and βarr2/MEX3A complexes, thus blocking the IGF-1R-triggered RIG-I degradation. Degradation of RIG-I resulted in the suppression of the IFN-I-associated immune cells in the TME due to the blockade of the RIG-I-MAVS-IFN-I pathway. Poly(I:C) could reverse anti-PD-L1 insensitivity by recovery of RIG-I. In summary, we revealed a disobliging IGF-1R signaling by which IGF-1Rβ promoted cancer growth through triggering the MEX3A-mediated degradation of RIG-I.

Challenges and Perspectives in Target Identification and Mechanism Illustration for Chinese Medicine / 中国结合医学杂志

Chinese medicine (CM) is an important resource for human life understanding and discovery of drugs. However, due to the unclear pharmacological mechanism caused by unclear target, research and international promotion of many active components have made little progress in the past decades of years. CM is mainly composed of multi-ingredients with multi-targets. The identification of targets of multiple active components and the weight analysis of multiple targets in a specific pathological environment, that is, the determination of the most important target is the main obstacle to the mechanism clarification and thus hinders its internationalization. In this review, the main approach to target identification and network pharmacology were summarized. And BIBm (Bayesian inference modeling), a powerful method for drug target identification and key pathway determination was introduced. We aim to provide a new scientific basis and ideas for the development and international promotion of new drugs based on CM.

Metabolomics study of Berberidis Radix in intervening ulcerative colitis based on UPLC-Q-TOF-MS / 中国中药杂志

The effect of Tujia medicine Berberidis Radix on endogenous metabolites in the serum and feces of mice with ulcerative colitis(UC) induced by dextran sulfate sodium(DSS) was analyzed by metabolomics technology to explore the metabolic pathway and underlying mechanism of Berberidis Radix in the intervention of UC. The UC model was induced in mice by DSS. Body weight, disease activity index(DAI), and colon length were recorded. The levels of tumor necrosis factor-α(TNF-α) and interleukin-10(IL-10) in colon tissues were determined by ELISA. The levels of endogenous metabolites in the serum and feces were detected by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were employed to characterize and screen differential metabolites. The potential metabolic pathways were analyzed by MetaboAnalyst 5.0. The results showed that Berberidis Radix could significantly improve the symptoms of UC mice and increase the level of the anti-inflammatory factor IL-10. A total of 56 and 43 differential metabolites were identified in the serum and feces, respectively, belonging to lipids, amino acids, fatty acids, etc. After the intervention by Berberidis Radix, the metabolic disorder gradually recovered. The involved metabolic pathways included biosynthesis of phenylalanine, tyrosine, and tryptophan, linoleic acid metabolism, phenylalanine metabolism, and glycerophospholipid metabolism. Berberidis Radix can alleviate the symptoms of mice with DSS-induced UC, and the mechanism may be closely related to the re-gulation of lipid metabolism, amino acid metabolism, and energy metabolism.

Opportunities, challenges and suggestions for the development of plastic degradation and recycling under the context of circular bioeconomy / 生物工程学报

At present, the negative impact caused by white pollution has spread to all aspects of human society economy, ecosystem, and health, which causes severe challenges for developing the circular bioeconomy. As the largest plastic production and consumption country in the world, China has shouldered an important responsibility in plastic pollution control. In this context, this paper analyzed the relevant strategies of plastic degradation and recycling in the United States, Europe, Japan and China, measured the literature and patents in this field, analyzed the status quo of technology from the perspective of research and development trends, major countries, major institutions, and discussed the opportunities and challenges faced by the development of plastic degradation and recycling in China. Finally, we put forward future development suggestions which include the integration of policy system, technology path, industry development and public cognition.

Recent advances in small molecule inhibitors of interleukin‑1 receptor-associated kinase / 药学学报

Interleukin-1 receptor associated kinase 4 (IRAK-4), acting as a serine threonine kinase, is considered as a key signal node for the transduction of IL-1R family and TLRs signal pathway. Studies have found that IRAK-4 has a hand in many signal pathways, involving the inflammatory response of human joints, intestines, liver and nervous system, as well as other autoimmune diseases. It is also one of the causes of drug resistance of some cancer cells. Therefore, IRAK-4 tends to be an effective therapeutic target for inflammatory diseases and cancer. The prospects for the development of drugs in this pathway is to develop novel IRAK-4 small molecule inhibitors and investigate their safety and effectiveness, enrich the clinical treatment of inflammatory and cancer diseases finally. This paper classified and summarized the latest research progress on small molecule inhibitors of IRAK-4 signaling pathway according to structures of the compounds, in order to provide assistances and references for the research and development of related drugs.

Study on the Emotional Status and Rights Protection of Participants in Drug Clinical Trials during Epidemic Prevention and Control / 中国医学伦理学

【Objective:】 To analyze the emotional status and follow-up status of the participants in the drug clinical trials in a hospital during the epidemic prevention and control, with a view to maximizing the protection of participants’ rights and interests under special circumstances. 【Methods:】 The general information, depression screening scale (PHQ-9), anxiety screening scale (GAD-7) and subject compliance assessment scale were completed online by participants with gold data questionnaire. At the same time, the status of drug clinical trials under study and the follow-up status of participants under study were collected from November 1, 2021 to December 8, 2021 and from December 9, 2021 to January 24, 2022. Excel software and SPSS18.0 software were used for data statistics and analysis. 【Results:】 During the epidemic prevention and control, there were 20 drug clinical trial projects under way in the hospital. From December 9, 2021 to January 24, 2022, the planned number of visits was 161, and the actual number of visits to the hospital was 84 (52.2%). Plus 24 participants who mailed drugs, the overall visit rate was 67.1%, among which the visit rates of oral drugs, non-oral drugs, and oral drugs combined with non-oral drugs were 79.3%, 71.9%, and 41.0% respectively. From November 1, 2021 to December 8, 2021, the planned number of visits was 166, the actual number of visits to the hospital was 157 (94.6%), and the number of telephone visits accounted for 1.8% of the total planned number of visits. The number of participants who did not take the drug and those who delayed taking the drug were both 0. The total compliance of participants was as high as 80.0%. A total of 40 valid questionnaires were retrieved, and the detection rates of depression and anxiety were 42.5% and 30.0% respectively. 【Conclusion:】 The epidemic prevention and control has a large short-term impact on the follow-up of the participants under study. The formulation of relevant follow-up measures and the conduction of classification management can not only improve the emotions of the participants to a certain extent, but also protect the rights and interests of participants, providing suggestions for the follow-up of participants under emergencies in the future.

Recent advances of small molecule inhibitors directly targeting HBV / 药学学报

Hepatitis B virus infection is a serious threat to human life and health. The approved anti-HBV drugs including interferons and nucleos(t)ide analogues have serious adverse effect, rebound phenomena after drug withdrawal, and drug resistance. And the cccDNA cannot be completely eliminated by both of them, which is the reason why a complete cure for hepatitis B cannot be achieved. Therefore, developing anti-HBV drugs directly targeting protein or nucleic acid of HBV remains a current public health priority. Based on the analysis of representative literature from the last decade, this article reviews recent developments in small molecule inhibitors directly targeting HBV from a medicinal chemistry perspective.

Advances in research on small molecule regulators targeting HBV cccDNA generation and transcription / 药学学报

Hepatitis B virus (HBV) represents a significant global public health challenge. Despite the availability of several approved drugs for hepatitis B treatment, the persistence of covalently closed circular DNA (cccDNA) renders HBV eradication elusive, thereby leading to disease relapse after drug withdrawal. This paper reviews the regulatory mechanisms of cccDNA formation, transcription and replication, and summarizes the research progress of related small molecule regulators from the perspective of medicinal chemistry.

Change in expression of tumor necrosis factor receptor-associated factor 6 in lung tissues of rats with pulmonary hypertension / 中华麻醉学杂志

Objective:To determine the change in the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6) in lung tissues of rats with pulmonary hypertension (PH).Methods:Sixteen SPF-grade healthy male Sprague-Dawley rats, aged 8 weeks, weighing 200-220 g, were divided into 2 groups ( n=8 each) by the random number table method: control group (group C1) and PH group (group PH1). The model of PH was prepared by subcutaneous injection of monocrotaline. On day 28 after developing the model, the mean pulmonary arterial pressure (mPAP) was measured, and the Fulton index was calculated, and the percentage of media wall thickness of the small and medium pulmonary arteries and percentage of muscularized vessels were also calculated. The expression of TRAF6, transcription-3 (STAT3), phosphorylated STAT3 (p-STAT3) and Cyclin D1 in lung tissues was detected by Western blot, and p-STAT3/STAT3 ratio was calculated. The interaction between TRAF6 and STAT3 was determined by immunoprecipitation assay. Primarily cultured pulmonary artery smooth muscle cells of normal rats (group C2) and pulmonary artery smooth muscle cells of rats with PH (group PH2) were inoculated in 6-well plates ( n=3 each). The expression of TRAF6 mRNA was detected by quantitative polymerase chain reaction. The expression of TRAF6, STAT3, p-STAT3 and Cyclin D1 was detected by Western blot. Results:Compared with group C1, the mPAP, Fulton index, percentage of media wall thickness of the small and medium pulmonary arteries and percentage of muscularized vessels were significantly increased, the expression of TRAF6 and Cyclin D1 in lung tissues was up-regulated, the p-STAT3/STAT3 ratio was increased ( P<0.05 or 0.01), and the results of immunoprecipitation showed that TRAF6 interacted with STAT3 in group PH1. Compared with group C2, the expression of TRAF6 protein and mRNA and Cyclin D1 was significantly up-regulated, and the p-STAT3/STAT3 ratio was increased in group PH2 ( P<0.05 or 0.01). Conclusions:The expression of TRAF6 in the lung tissue is up-regulated in rats with PH, which may be related to pulmonary vascular remodeling by promoting the activation of STAT3.

Environmental and health effects of nuclear wastewater —Something beyond Fukushima nuclear wastewater discharge / 中国辐射卫生

In April 2021, the Japanese government decided to discharge nuclear wastewater from the Fukushima Daiichi nuclear power plant into the sea, which aroused widespread concern all over the world. The radioactive substances in nuclear wastewater may affect the environment through the action of ocean circulation, groundwater or carbon cycle. In addition, it may expose people to the health effects of low-dose but long-term pollution once nuclear wastewater is discharged into the sea. Based on this, this paper discusses the possible global environmental impact of nuclear wastewater from a general perspective and illustrates its possible health effects as well as potential mental health problems from an individual perspective, and puts forward some suggestions on the issue of Fukushima nuclear wastewater discharge.

Clinical characteristics of lung cancer associated acute ischemic stroke and atrial fibrillation associated acute ischemic stroke / 中国医师杂志

Objective:To analyze the clinical characteristics of lung cancer associated acute ischemic stroke (LCA-AIS) and atrial fibrillation associated acute ischemic stroke (AFA-AIS).Methods:From January 1, 2014 to December 31, 2018, 46 patients diagnosed with LCA-AIS (LCA-AIS group)in Hainan Hospital of Chinese PLA General Hospital were selected, and 46 patients diagnosed with AFA-AIS (AFA-AIS group) were matched according to age and sex.The general situation, laboratory test results and imaging results of the two groups were analyzed.Results:(1) The neurological deficit symptoms in AFA-AIS group were more serious than those in LCA-AIS group; there was significant difference in National Institutes of Health Stroke Scale (NIHSS) score and the Modified Rankin Scale (mRs) score between the two groups ( P=0.001, P=0.003). (2)The D-D polymer concentration in LCA-AIS group was significantly higher than that in AFA-AIS group ( P<0.001), but the hemoglobin, erythrocyte count and hematocrit were significantly lower than those in AFA-AIS group (all P<0.001). (3)There was no significant difference in imaging classification and the number of infarct basins between LCA-AIS group and AFA-AIS group ( P>0.05). LCA-AIS patients was more likely to have poly-period acute ischemic lesions ( P=0.015), while AFA-AIS had significantly larger infarct diameter and more likely to be complicated with acute hemorrhagic stroke or bleeding ( P<0.001). Conclusions:The clinical characteristics of LCA-AIS and AFA-AIS are similar, so it is necessary to distinguish LCA-AIS from AFA-AIS in combination with neurological impairment, laboratory tests and imaging findings to avoid misdiagnosis.

Impact of dispatcher-assisted cardiopulmonary resuscitation on survival after out-of-hospital cardiac arrest: A Meta-analysis / 中华急诊医学杂志

Objective:To evaluate the outcome of the patients receiving dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) delivered by first-responders who witnessed the out-of-hospital cardiac arrest (OHCA) before the Emergency Medical Service (EMS) arrived.Methods:We performed a search of the relevant literature exploring major scientific databases. We assessed the quality of the included cohort study according to the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. Meta-analysis was performed on three outcome indicators (recovery of spontaneous circulation survival to hospital discharge and survival with favourable neurologic outcome) using the Revman5.3 software.Results:A total of 21 studies with 349 822 patients were selected for the meta-analysis, including 182 125 patients in the DA-CPR group and 167 697 in the CPR-only group. The meta-analysis showed no significant difference between the DA-CPR and CPR-only groups in ROSC [ RR=1.10, 95% confidence interval ( CI): 0.94-1.29, P=0.24], survival to hospital discharge ( RR=1.10, 95% CI: 0.90-1.34, P=0.34) and survival with favourable neurologic outcome ( RR=1.01, 95% CI: 0.79-1.28, P=0.97) of the patients in America, Japan and Korea. However, there was a significant difference between the DA-CPR and the CPR-only groups in ROSC ( RR=2.61, 95% CI:1.53-4.46, P=0.0005), survival to hospital discharge( RR=6.08, 95% CI: 1.84-20.04, P=0.003), and survival with favourable neurologic outcome( RR=9.76, 95% CI: 1.87-51.02, P=0.007) of the patients in China. Conclusions:The overall effect of DA-CPR is significantly different for each country. In detail, DA-CPR offers a survival advantage (Return of spontaneous circulation, survival to hospital discharge and survival with favourable neurologic outcome) over CPR alone in China but no advantage in developed countries.

Serum mitochondrial tsRNA serves as a novel biomarker for hepatocarcinoma diagnosis / 医学前沿

Hepatocellular carcinoma (HCC), which makes up the majority of liver cancer, is induced by the infection of hepatitis B/C virus. Biomarkers are needed to facilitate the early detection of HCC, which is often diagnosed too late for effective therapy. The tRNA-derived small RNAs (tsRNAs) play vital roles in tumorigenesis and are stable in circulation. However, the diagnostic values and biological functions of circulating tsRNAs, especially for HCC, are still unknown. In this study, we first utilized RNA sequencing followed by quantitative reverse-transcription PCR to analyze tsRNA signatures in HCC serum. We identified tRF-Gln-TTG-006, which was remarkably upregulated in HCC serum (training cohort: 24 HCC patients vs. 24 healthy controls). In the validation stage, we found that tRF-Gln-TTG-006 signature could distinguish HCC cases from healthy subjects with high sensitivity (80.4%) and specificity (79.4%) even in the early stage (Stage I: sensitivity, 79.0%; specificity, 74.8%; 155 healthy controls vs. 153 HCC patients from two cohorts). Moreover, in vitro studies indicated that circulating tRF-Gln-TTG-006 was released from tumor cells, and its biological function was predicted by bioinformatics assay and validated by colony formation and apoptosis assays. In summary, our study demonstrated that serum tsRNA signature may serve as a novel biomarker of HCC.

Effects of high-fat diet in pre-pregnancy and pregnancy-and-lactation periods on gut microbiota of offspring mice / 环境与职业医学

Background In recent years gut microbiota has been found to play an important role in the occurrence and development of various chronic diseases, and diet is an important factor influencing gut microbiota. However, the effects of maternal high-fat diet in pre-pregnancy and pregnancy-and-lactation periods on offspring gut microbiota are still unclear. Objective To investigate the effects of maternal high-fat diet in pre-pregnancy and pregnancy-and-lactation periods on gut microbiota of offspring mice. Methods C57BL/6J female mice were divided into four groups according to the diet patterns (high-fat diet, HFD; control diet, CD) given before and after conception, namely the pre-pregnancy control diet and post-pregnancy control diet group (CD-CD group), the pre-pregnancy control diet and post-pregnancy high-fat diet group (CD-HFD group), the pre-pregnancy high-fat diet and post-pregnancy control diet group (HFD-CD group), and the pre-pregnancy high-fact diet and post-pregnancy high-fat diet group (HFD-HFD group). Female mice were conceived in the same cage with male mice after 6 weeks of feeding, and the successfully conceived females continued to be randomly divided into two groups receiving either high-fat or control diet, and when the offspring mice were born, they were breastfed directly by the mothers, with each mother nursing only one offspring mouse. The number of offspring mice in each group was 6, with half males and half females. The body weight of offspring mice were recorded and body weight gain was compared between the four groups. After the lactational period, fresh feces of the offspring were collected, and the fecal DNA was extracted. Specific primers were designed according to the bacterial 16S rDNA(V3+V4) sequence and then the sequencing was performed using the Illumina HiSeq 2500 platform. Species annotation and operational taxonomic unit (OTU) analysis of sequencing data were conducted using QIMME, USEARCH and R software. In alpha diversity analysis, ACE and Chao1 indices were used to evaluate species richness, Shannon and Simpson indices considered both species richness and evenness. In beta diversity analysis, principal coordinates analysis (PCoA) and analysis of similarities (Anosim analyses) were used to find the differences in composition of gut microbiota between four groups, and line discriminant analysis effect size (LefSe) was conducted to identify which specific taxa contributed to the significant differences between groups. Results A greater effect of post-pregnancy diet on offspring body weight was observed, and the lowest body weight was recorded in the HFD-CD group during the whole experimental period. The results of OTU analysis showed that high-fat diet during post-pregnancy period reduced the number of OTUs in offspring mice, and the results of alpha diversity analysis showed that high-fat diet during post-pregnancy period reduced the richness of intestinal flora (ACE, P<0.05; Chao1, P<0.05), whereas differences in the α-diversity indices did not show statistical significance in the offspring mice with pre-pregnancy high-fat diet. The high-fat diet at different periods also led to changes in the dominant intestinal flora of the offspring. The high-fat diet during post-pregnancy period increased the abundance of Tenericutes (P<0.05), and decreased the abundance of Bacteroides, Epsilonbacteraeota, Cyanobacteria, and Deferribacteres (all Ps<0.05). At the genus level, high-fat diet during both pre-pregnancy and post-pregnancy periods decreased the abundance of Lactobacillus (P<0.05), and high-fat diet during pre-pregnancy period increased the abundance of Alistipes (P<0.05), while high-fat diet during post-pregnancy period increased the abundance of Lachnospira and Ruminococcus, and decreased the abundance of Muribaculaceae and Helicobacter (all Ps<0.05). The results of beta diversity analysis showed that the CD-CD group had a similar flora composition to the HFD-CD group, and the CD-HFD group had a similar flora composition to the HFD-HFD group, and the results of Anosim analysis showed statistically significant differences between groups (R=0.743, P<0.01). The LEfSe analysis counted all species with an effect on the differences between groups greater than the set value, which were Lactobacillus in the CD-CD group, Clostridiales in the CD-HFD group, Bacteroidetes and Helicobacters in the HFD-CD group, and Blautia, Ruminococcaceae, and Roseburia in the HFD-HFD group. Conclusion It is found that varied effects of high-fat diet in different periods on the flora of the offspring mice. The high-fat diet during pre-pregnancy and post-pregnancy periods could reduce the abundance of Lactobacillus, but show different effects on the abundance of other intestinal flora such as Muribaculaceae, Lachnospiraceae, and Helicobacter differed. Diet during post-pregnancy period has a greater influence on modeling the offspring gut microbiota.

The effects of exercise on the renin-angiotensin system in blood and skeletal muscle after heart failure / 中华物理医学与康复杂志

Objective:To observe the effect of exercise on the renin-angiotensin system (RAS) in the blood and skeletal muscles of rats with chronic heart failure (CHF).Methods:Fifty male Wistar rats were randomly divided into a sedentary control group, an exercise control group, a model sedentary group and a model exercise group. CHF was modelled in the rats of the model sedentary and exercise groups, while those of the sedentary and exercise control groups received a sham operation. The exercise groups performed treadmill exercise for 8 weeks (5 times per week). After the 8 weeks the activity of angiotensin-converting enzyme (ACE) and ACE2 in the plasma and soleus muscle was determined using the fluorescent substrate method. Angiotensin II (AngII) and Ang (1-7) were detected in plasma and the soleus muscle using liquid chromatography. The expression of Ang II type 1 receptor (AT1R) and Mas receptor (MasR) in skeletal muscles was detected using western blotting.Results:Compared with the sedentary control group, there was significantly increased average ACE activity and lower average ACE2 activity in the model sedentary group. There was a significant decrease in the average plasma Ang II content and ACE activity, and a significant increase in the Ang-(1-7)/Ang II ratio in the model exercise group. Compared with the model sedentary group, the average ACE activity and plasma Ang II content was significantly lower in the model exercise group but the average ACE2 activity was significantly higher. Compared with the sedentary control group, the average Ang II content and AT1R protein expression in the soleus muscles had increased significantly in the model sedentary group, and the average expression of MasR protein in the soleus muscles increased significantly in the model exercise group. However, compared with the model sedentary group, the average content of Ang II and the average expression of AT1R protein in the soleus muscles had decreased significantly in the model exercise group and the average Ang-(1-7)/Ang II ratio had increased significantly.Conclusion:Exercise can induce the conversion of RAS from ACE-Ang II-AT1R to ACE2-Ang-(1-7)-MasR after chronic heart failure, at least in rats. The changes in the components of the RAS in the plasma and skeletal muscle differ.