Seven new triterpenoids from the roots of Adenophora tetraphylla (Thub.) Fisch.

Seven new triterpenoids, named Adeterpenoids A-G (1-7) and eight known compounds (8-15), were isolated from 70% ethanol extract of the roots of Adenophora tetraphylla (Thub.) Fisch. The compounds from it were separated by column chromatography techniques such as silica gel, ODS, and preparative liquid chromatography. Their structures were clarified based on extensive spectral analysis (1D, 2D-NMR, HR-ESI-MS, IR, UV, and CD) and comparison with the literature. At the same time, all compounds were evaluated for their cytotoxic activity against the LN229 (human glioma cell line). The results showed that compounds 2, 5, 6, 13, and 14 had a significant inhibitory effect on LN229 cells.

Effect of Resistance Training Combined with Beta-Hydroxy-Beta-Methylbutyric Acid Supplements in Elderly Patients with Sarcopenia after Hip Replacement.

OBJECTIVES: To evaluate the efficacy of resistance training (RT) combined with beta-hydroxy-beta-methylbutyric acid (HMB) in the treatment of elderly patients with sarcopenia after hip replacement. METHODS: From January 1, 2018 to December 31, 2018, 200 elderly patients (68 men, mean age 76.3 years and 137 women, mean age 79.1 years) who experienced femoral neck fracture with sarcopenia after hip arthroplasty were assigned to four groups: RT + HMB group, RT group, HMB group, and negative control group. Baseline data, body composition, grip strength, Barthel index (BI), Harris hip score (HHS), and visual analog scale score (VAS) were compared among the four groups before and 3 months after surgery. RESULTS: A total of 177 participants completed the trial, including 43 in the HMB + RT group, 44 in the HMB group, 45 in the RT group, and 45 in the negative control group. At the 3-month follow-up, the body composition and grip strength of the HMB + RT group and RT group were significantly improved compared with those before operation. The HMB group had no significant change, while the measures in the negative control group significantly decreased. Postoperative BI and HSS did not reach pre-injury levels in any of the four groups, but postoperative VAS score was significantly improved. However, there was no significant difference in BI, HSS, or VAS among the four groups. CONCLUSION: RT, with or without HMB supplementation, can effectively improve body composition and grip strength in elderly patients with sarcopenia after hip replacement at short-term follow-up. Simultaneously, use of exclusive HMB supplementation alone may also help to prevent decreases in muscle mass and grip strength in these patients.

The Potential Prebiotic Berberine Combined With Methimazole Improved the Therapeutic Effect of Graves' Disease Patients Through Regulating the Intestinal Microbiome.

Graves' disease, a typical metabolism disorder, causes diffuse goiter accompanied by ocular abnormalities and ocular dysfunction. Although methimazole (MI) is a commonly used drug for the treatment of GD, the efficacy of methimazole is only limited to the control of clinical indicators, and the side effects of MI should be seriously considered. Here, we designed a 6-month clinical trial that divided the patients into two groups: a methimazole group (n=8) and a methimazole combined with potential prebiotic berberine group (n=10). The effects of both treatments on thyroid function and treatment outcomes in patients with GD were assessed by thyroid index measurements and gut microbiota metagenomic sequencing. The results showed that the addition of berberine restored the patients' TSH and FT3 indices to normal levels, whereas MI alone restored only FT3. In addition, TRAb was closer to the healthy threshold at the end of treatment with the drug combination. MI alone failed to modulate the gut microbiota of the patients. However, the combination of berberine with methimazole significantly altered the microbiota structure of the patients, increasing the abundance of the beneficial bacteria Lactococcus lactis while decreasing the abundance of the pathogenic bacteria Enterobacter hormaechei and Chryseobacterium indologenes. Furthermore, further mechanistic exploration showed that the addition of berberine resulted in a significant upregulation of the synthesis of enterobactin, which may have increased iron functioning and thus restored thyroid function. In conclusion, methimazole combined with berberine has better efficacy in patients with GD, suggesting the potential benefit of berberine combined with methimazole in modulating the composition of intestinal microbes in the treatment of GD, providing new strong evidence for the effectiveness of combining Chinese and Western drugs from the perspective of modulating the intestinal microbiota.

Superfine pulverisation pretreatment to enhance crystallinity of cellulose from Lycium barbarum L. leaves.

Superfine pulverisation (SFP) pretreatment of Lycium barbarum L. leaves was performed to obtain highly crystalline cellulose. Compared with other common pulverisation methods, SFP enhanced cellulosic crystallinity by 18.3 % and 8.4 %, with and without post-acid treatments, respectively. XRD and solid-state NMR analyses showed that SFP facilitated the exposure of amorphous substances (i.e., hemicellulose and lignin) to NaOH and H2O2. Large amounts of silicon (5.5 %) and aluminium (2.1 %) were found to incorporate into the crystalline regions of SFP-produced cellulose. Further FTIR and thermogravimetric analyses revealed that SFP-produced cellulose contained large amounts of hydroxyl groups, affecting the cellulosic crystallinity and thermal stability. These findings demonstrate the potential for SFP to serve as a green technology for production of highly crystalline and mineral-rich cellulose.

Effects of Atorvastatin Combined with Nano-Selenium on Blood Lipids and Oxidative Stress in Atherosclerotic Rats.

Dyslipidemia and oxidative stress injury of blood vessel walls play important roles in the formation of atherosclerosis (AS) and plaque progression. This is also the main pathological basis for atherosclerosis. Statins, as inhibitors of HMG-CoA reductase in the process of cholesterol biosynthesis, have become key drugs for lipid-lowering treatment. Many studies have found the anti-atherosclerotic effect of atorvastatin is far beyond the lipid-lowering effect. Its lipid-lowering effects are also involved, such as anti-inflammatory, inhibiting endothelial cell ROS production, and improving endothelial cell damage. Nano selenium (Nano-Se) shows stronger anti-oxidation ability, lower toxicity, high efficiency absorption and strong immune regulation ability. Because of the unique biological effects of Nano-Se, it has broad prospects in the field of human health care. Therefore, in this study, by constructing a rat model of abnormal lipid metabolism, we observed changes in parameters such as serum peroxidase (MPO), propylene glycol (MDA), superoxide dismutase (SOD), and blood lipid levels in atherosclerotic rats Happening, furthermore, the effects of atorvastatin+nano-selenium on lipid metabolism disorders and the protective effects and mechanisms of oxidative stress injury in rats were investigated and with a view to providing new targets for the treatment of arteriosclerosis. The results of this study demonstrated that contrast to the AS rat, the combined use of atorvastatin+nano-selenium group could significantly reduce serum TC, TG, and LDL-C contents, and declined tissue lesions such as aortic arch and liver; Significantly enhanced the activities of GPx-1 and SOD in serum, decreased MDA content, and increased the SOD activity in rat aorta. These results suggested that the combined use of atorvastatin+nano-selenium has good protection against oxidative stress caused by disorders of lipid metabolism.

Sodium nitrite negatively affects reproductive ability and offspring survival in female mice.

Sodium nitrite (NaNO2) is an industrial chemical that is frequently used as a food additive to prevent botulism and enhance glossiness, such as curing meat. In addition, in some regions, water source NaNO2 concentrations exceed standard regulatory levels. Whether the excessive intake of NaNO2 has toxic effects on female fertility and fetal development remain unknown. In this study, we administered ICR mice control saline, low-dose NaNO2 (60 mg/kg/day), or high-dose NaNO2 (120 mg/kg/day) by intragastric gavage for 21 days. We then assessed oocyte morphology, spindle-chromosome dynamics, mitochondrial distribution, ATP content, apoptotic cell numbers, DNA damage levels, histone modifications, reactive oxygen species (ROS) levels, and offspring survival. Results showed that NaNO2 treatment decreased oocyte number, impaired polar body extrusion, and increased zona pellucida thickness in oocytes. Furthermore, NaNO2 disrupted MII spindle integrity, caused abnormal mitochondrial distribution, decreased ATP content, and increased levels of ROS and H3K4me2. Moreover, the number of oocytes in early stages of apoptosis and with levels of DNA damage increased in NaNO2-treated mice along with decreased offspring numbers and survival rates. We demonstrated the negative effects of NaNO2 on female reproductive abilities in mice.

Triptolide Restores Autophagy to Alleviate Diabetic Renal Fibrosis through the miR-141-3p/PTEN/Akt/mTOR Pathway.

Fibrosis is the major pathological feature of diabetic kidney disease (DKD). Autophagy, a process to maintain metabolic homeostasis, is obviously inhibited in DKD. Triptolide (TP) is a traditional Chinese medicine extract known for immune suppression and anti-inflammatory and anti-cancer activities. In this study, we investigated the effects of TP on autophagy and fibrosis in DKD. TP restored autophagy and alleviated fibrosis in DKD rats and high-glucose-incubated human mesangial cells. After we applied 3-methyladenine (an autophagy inhibitor) and autophagy-related gene 5-small interfering RNA (siRNA), we found that the improvement of fibrosis on TP was related to the restoration of autophagy. In addition, miR-141-3p levels were increased under high glucose but reduced after TP treatment. miR-141-3p overexpression aggravated the fibrosis and restrained the autophagy further, while miR-141-3p inhibition imitated the effects of TP. As an action target, phosphatase and tensin homolog (PTEN) showed corresponding opposite changes. After PTEN-siRNA transfection, the effects of TP on autophagy and fibrosis were inhibited. PTEN levels were downregulated, with downstream phosphorylated protein kinase B (Akt) and the mammalian target of rapamycin (mTOR) upregulated in high glucose, which were reversed by TP treatment. These findings indicate that TP alleviates fibrosis by restoring autophagy through the miR-141-3p/PTEN/Akt/mTOR pathway and is a novel therapeutic option for DKD.

Tongxinluo Inhibits Renal Fibrosis in Diabetic Nephropathy: Involvement of the Suppression of Intercellular Transfer of TGF-[Formula: see text]1-Containing Exosomes from GECs to GMCs.

Glomerular mesangial cells (GMCs) activation is implicated in the pathogenesis of diabetic nephropathy (DN). Our previous study revealed that high glucose (HG)-treated glomerular endothelial cells (GECs) produce an increased number of TGF-[Formula: see text]1-containing exosomes to activate GMCs through the TGF-[Formula: see text]1/Smad3 signaling pathway. We also identified that Tongxinluo (TXL), a traditional Chinese medicine, has beneficial effects on the treatment of DN in DN patients and type 2 diabetic mice. However, it remained elusive whether TXL could ameliorate renal structure and function through suppression of intercellular transfer of TGF-[Formula: see text]1-containing exosomes from GECs to GMCs. In this study, we demonstrate that TXL can inhibit the secretion of TGF-[Formula: see text]1-containing exosomes from HG-treated GECs. Furthermore, exosomes produced by HG induced-GECs treated with TXL cannot trigger GMC activation, proliferation and extracellular matrix (ECM) overproduction both in vitro and in vivo. These results suggest that TXL can prevent the transfer of TGF-[Formula: see text]1 from GECs to GMCs via exosomes, which may be one of the mechanisms of TXL in the treatment of DN.

A Personalized Model of COQ2 Nephropathy Rescued by the Wild-Type COQ2 Allele or Dietary Coenzyme Q10 Supplementation.

Clinical studies have identified patients with nephrotic syndrome caused by mutations in genes involved in the biosynthesis of coenzyme Q10 (CoQ10), a lipid component of the mitochondrial electron transport chain and an important antioxidant. However, the cellular mechanisms through which these mutations induce podocyte injury remain obscure. Here, we exploited the striking similarities between Drosophila nephrocytes and human podocytes to develop a Drosophila model of these renal diseases, and performed a systematic in vivo analysis assessing the role of CoQ10 pathway genes in renal function. Nephrocyte-specific silencing of Coq2, Coq6, and Coq8, which are genes involved in the CoQ10 pathway that have been associated with genetic nephrotic syndrome in humans, induced dramatic adverse changes in these cells. In particular, silencing of Coq2 led to an abnormal localization of slit diaphragms, collapse of lacunar channels, and more dysmorphic mitochondria. In addition, Coq2-deficient nephrocytes showed elevated levels of autophagy and mitophagy, increased levels of reactive oxygen species, and increased sensitivity to oxidative stress. Dietary supplementation with CoQ10 at least partially rescued these defects. Furthermore, expressing the wild-type human COQ2 gene specifically in nephrocytes rescued the defective protein uptake, but expressing the mutant allele derived from a patient with COQ2 nephropathy did not. We conclude that transgenic Drosophila lines carrying mutations in the CoQ10 pathway genes are clinically relevant models with which to explore the pathogenesis of podocyte injury and could serve as a new platform to test novel therapeutic approaches.

Social media as a tool for antimicrobial stewardship.

BACKGROUND: To increase the reach of our antimicrobial stewardship program (ASP), social media platforms, Facebook and Twitter, were used to increase internal medicine residents' (IMRs') antibiotic (Abx) knowledge and awareness of ASP resources. METHODS: Fifty-five of 110 (50%) IMRs consented to participate; 39 (71%) completed both pre- and postintervention surveys and followed our ASP on social media. Along with 20 basic Abx and infectious diseases (IDs) questions, this survey assessed IMR awareness of ASP initiatives, social media usage, and attitudes and beliefs surrounding Abx resistance. Over 6 months, IMRs received posts and Tweets of basic Abx/IDs trivia while promoting use of educational tools and clinical pathways on our ASP Web site. To compare pre- and postsurvey responses, McNemar test or Stuart-Maxwell test was used for categorical variables, and paired t test or Wilcoxon signed-rank test was used for continuous variables, as appropriate. RESULTS: Of the IMRs, 98% and 58% use Facebook and Twitter, respectively. To compare pre- and postintervention, median scores for Abx knowledge increased from 12 (interquartile range, 8-13) to 13 (interquartile range, 11-15; P = .048); IMRs knowing how to access the ASP Web site increased from 70% to 94%. More IMRs indicated that they used the clinical pathways "sometimes, frequently, or always" after the intervention (33% vs 61%, P = .004). CONCLUSIONS: Social media is a valuable tool to reinforce ASP initiatives while encouraging the use of ASP resources to promote antimicrobial mindfulness.

Protective effects of Semen Crotonis Pulveratum on trinitrobenzene sulphonic acid-induced colitis in rats and H2O2-induced intestinal cell apoptosis in vitro.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease. Semen Crotonis Pulveratum (SCP) has been used as a traditional medicine for the treatment of UC. However, its molecular mechanisms of action have not yet been elucidated. In the present study, we aimed to investigate the preliminary mechanisms of the role of SCP on trinitrobenzene sulphonic acid (TNBS)-induced UC in rats and hydrogen peroxide (H2O2)-induced intestinal cell apoptosis in vitro. Wistar rats (n=9 per group) were randomly divided into 4 groups: the normal control group, the UC group, the UC + SCP group and the UC + sulfasalazine group as a positive control. The proportion of CD4+CD25+ T cells and CD4+CD25+Foxp3+ Tregs, and the expression levels of interleukin (IL)-6 and IL-10 in the peripheral blood, as well as the expression levels of cyclooxygenase-2 (COX-2) and intercellular adhesion molecule-1 (ICAM-1) in the colon tissues were determined by flow cytometry, ELISA and immunohistochemical staining, respectively. Rat intestinal epithelial (IEC-6) cell apoptosis induced by H2O2 was determined by TUNEL assay, flow cytometry using Annexin V/propidium iodide (PI) staining and western blot analysis of caspase-3 activation, respectively. Significantly higher proportions of circulating CD4+CD25+ T cells and CD4+CD25+Foxp3+ Tregs were present in the UC + SCP group compared with the UC group. A significantly decreased expression of IL-6 and an increased expression of IL-10 were also observed in the UC + SCP group compared with UC group. SCP significantly reduced the UC-induced increase in the expression of COX-2 and ICAM-1 in the colon tissues. SCP inhibited cell apoptosis and caspase-3 activation induced by H2O2 in the ICE-6 cells. Our data thus indicate that SCP inhibits inflammation in UC by increasing the proportion of circulating Tregs, altering cytokine production and decreasing COX-2 and ICAM-1 expression. In addition it protects against H2O2-induced intestinal cell apoptosis in vitro.

Naringin prevents ovariectomy-induced osteoporosis and promotes osteoclasts apoptosis through the mitochondria-mediated apoptosis pathway.

Naringin, the primary active compound of the traditional Chinese medicine Rhizoma drynariae, possesses many pharmacological activities. The present study is an effort to explore the anti-osteoporosis potential of naringin in vivo and in vitro. In vivo, we used ovariectomized rats to clarify the mechanisms by which naringin anti-osteoporosis. In vitro, we used osteoclasts to investigate naringin promotes osteoclasts apoptosis. Naringin was effective at enhancing BMD, trabecular thickness, bone mineralization, and mechanical strength in a dose-dependent manner. The result of RT-PCR analysis revealed that naringin down-regulated the mRNA expression levels of BCL-2 and up-regulated BAX, caspase-3 and cytochrome C. In addition, naringin significantly reduced the bone resorption area in vitro. These findings suggest that naringin promotes the apoptosis of osteoclasts by regulating the activity of the mitochondrial apoptosis pathway and prevents OVX-induced osteoporosis in rats.

A novel four-step system for screening angiogenesis inhibitors.

Angiogenesis exhibits a significant effect on tumor progression. Inhibiting angiogenesis may provide significant advantages over currently available therapeutics for cancer therapies thus, the development of a system of screening angiogenesis is essential. In the present study, a novel available system of screening angiogenesis inhibitors by four steps was developed. The chorioallantoic membrane (CAM), yolk sac membrane and early chick embryo blood island assay were initially performed to obtain possible antitumor compounds. The MMTV­PyMT transgenic breast cancer mouse model was used for final screening and to confirm potential antitumor effects. Four angiogenesis inhibitors were isolated from 480 compounds, which were obtained from ICCB known bioactives library, by a combination of the CAM, yolk sac membrane and early chick embryo blood island assay. The MMTV­PyMT mouse was treated with one of four agents and it was demonstrated that the tumor volume was significantly inhibited. These results demonstrate that the four­step screening system is feasible.

[Preparation, manipulation and clinical application of prof. HUANG Di-jun's moxibustion with seed-sized moxa cone].

Manipulation method and clinical application of Prof. HUANG Di-jun's moxibustion with seed-sized moxa cone are introduced from preparation of argyi wool, manipulation, matters needing attention, indications, and clinical characteristics of moxibustion with seed-sized moxa cone, etc. So as to popularize moxibustion with seed-sized moxa cone.